IM Platinum, 2nd Edition (1)

April 5, 2018 | Author: Janelle Estrabela Gargaritano | Category: Electrocardiography, Cardiovascular System, Cardiology, Medical Specialties, Cardiac Electrophysiology
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IM Platinum is a handy guide on Internal Medicine for students, residents, and consultants practing medicine....



Introduction to Internal Medicine


Normal Laboratory Values and Conversion Factors 1. Complete Blood Count 2. Blood Chemistry 3. Urine Studies 4. Equivalent Values


Intravenous Fluids 1. Intravenous Fluids and Common Indications


Commonly Used Drips 1. Formulation and Computation of Basic Drips 2. Other Commonly Used Drips

Core Skills in Internal Medicine 1. Electrocardiography 2. Chest Radiograph Interpretation 3. Arterial Blood Gas Interpretation 4. Thoracentesis 5. Paracentesis 6. Foley Catheter Insertion 7. Intravenous Line Insertion



INTRODUCTION TO INTERNAL MEDICINE I. INTRODUCTION Internal Medicine (IM) can be quite overwhelming because of the complexity of cases and long work hours. Despite these inherent toxicities, it remains one of the most rewarding fields in Medicine. Students and practitioners alike enjoy the intellectual stimulation and experience of translating theoretical knowledge into direct patient care. As basic IM principles cannot be dissociated from the cases we encounter, it is imperative for every practitioner to acquire the core competencies and skills of an internist. The approach to patient encounter and chart writing are discussed in the succeeding parts.

II. HISTORY AND PHYSICAL EXAMINATION Complete history and physical examination are central to hypothetico-deductive reasoning in clinical medicine. Starting from the chief complaint, problems are elicited from the in chronological order. After completing the details for acute complaints, probe into the patient’s past medical history, including present medications and pre-morbid functional capacity. Diseases in the family such as hypertension, diabetes, heart disease, early cardiac death and other heredofamilial diseases should be elicited as part of the family medical history. History of allergic reactions to drugs and food should always be elicited. Dietary habits, smoking history, alcohol intake and illicit drug use should also be included in the personal and social history. Likewise, female patients should be asked about details on menstruation and pregnancy. The comprehensive history is followed by the systematic physical examination (PE). This starts with a general survey followed by checking the patient’s vital signs. Permission should always be asked from the patient before doing any maneuver, especially the more intrusive ones. A complete PE is carried out with special focus on certain procedures pertinent to the identified problems of the patient.

III. WRITING THE ORDERS With the information obtained from the history and PE, a prioritized problem list is then created, with the most urgent conditions listed first. Based on the problem list, the management list is then outlined. The orders for the patient usually contain the following: Diet

Fluids and Drips


   

Diagnostics Therapeutics

 Transfusions

 

Dietary preparations (i.e., general liquids, soft diet, full diet) and specific dietary prescriptions (i.e., low-salt, low-fat, low-purine, DAT) Main IV lines (i.e., plain saline, D5-containing fluids) and side drips (i.e., vasopressors, electrolyte solutions) BP, HR, RR, temperature, peripheral O2 saturation, neurologic vitals, etc.) Frequency by which these parameters are checked (i.e., q hourly, q4h, q shift) Prioritized list of diagnostic procedures such as imaging, blood tests and special procedures Medications with corresponding doses, frequency of dosing, duration and side effects to watch out for Blood products, the amount to be transfused, rate of transfusion and interval between transfusions Pre-medications and side effects to watch out for Anticipatory measures: diuretics for possible congestion, anti-pyretics for febrile transfusion reactions


DATE/TIME 6/10/2015 7:30am

PHYSICIAN’S ORDER SHEET Gen Med Diagnosis: Community acquired pneumonia, moderate risk Hypertension, stage I, controlled Diet: Low salt, low fat diet; limit oral fluid intake 100bpm  Bradycardia: HR 120 msecs  P-waves, PR interval and QRS: normal


STEP 3: MEASURE INTERVALS Normal Values Wave/Interval P-wave PR interval QRS duration QT interval (QTc)

Description Atrial depolarization Conduction within the AV node Ventricular activation Ventricular activation and recovery

Normal Values < 0.12 sec or 3 small boxes) Biphasic P wave in V1 with a broad negative component Often notched P-wave in one or more limb leads “P-Mitrale” or M-shaped P-wave


B. Left Ventricular Hypertrophy (LVH) SOKOLOW-LYON CRITERIA [S in V1] + [R in V5 or v6] > 35 mm (>35 small boxes) OR

CORNELL CRITERIA S in V3 + R in aVL:  Female > 20mm  Male > 28mm

R in aVL>11mm C. Right Ventricular Hypertrophy (RVH)    

Relatively tall R wave in lead V1 (R > S wave) with right axis deviation R in V1 > 0.7mV R/S in V1 > 1 with R > 0.5 mV R/S in V5 or V6 < 1


JUNCTIONAL AND IDIOVENTRICULAR RHYTHMS A. Junctional (Atrioventricular) Rhythm    

Pacemaker: AV junction with a ventricular rate of 40 to 60 bpm P wave: may appear before, after, or buried within the QRS complex Rhythm (RR-interval): regular QRS complex: narrow (0.12 sec)



Temporary cessation of sinus node activity May be synonymous with sinus “arrest” – which pertains to a prolonged sinus pause (definition is arbitrary) Difference from sinus exit block: the supposed P-P interval of the dropped beat is not a multiple of the normal P-P interval

B. Sinus Exit Block  

Failure of impulse transmission No visible P-QRS-T complex for >1 cycle, wherein the P-P interval of the pause is a multiple of the normal P-P interval (differentiating it from sinus pause)


Prolonged PR interval (>0.20 sec or >5 small boxes) P-wave is followed by a QRS complex

B. Second Degree AV Block, Mobitz Type I (Wenckebach) 

PR interval progressively lengthens, then the impulse is blocked (P is not followed by QRS, resulting in a dropped beat)


C. Second Degree AV Block, Mobitz Type II 

PR intervals of conducted beats are constant in length, however, beats are dropped with no warning PR intervals may be normal or prolonged

D. High Grade AV Block 

2 out of every 3 or more impulses from the atria are blocked by the AV node and fail to reach the ventricles PR intervals are constant (in contrast to complete heart block)

E. Third Degree (Complete) AV Block 

P and QRS waves occur regularly but are independent of each other No consistent relationship between atrial and ventricular activity (AV Dissociation) PP intervals and RR intervals are constant


ATRIAL ARRHYTHMIAS A. Premature Atrial Contractions (PAC)  

Premature P-waves (earlier than the next expected sinus P-wave) P-wave has a different morphology compared to the sinus P-wave since this P-wave is coming from a different atrial focus QRS is usually narrow

B. Atrial Fibrillation (AF) 

   

Description: Rapid, erratic electrical discharge from multiple atrial ectopic foci Rate: atrial rate >350 bpm; ventricular rate varies Rhythm: irregularly irregular P-waves: no discernable P-wave QRS: usually normal

C. Atrial Flutter 

   

Description: Re-entrant circuit within the atria, with variable conduction of impulses through the AV node to the ventricles Rate: atrial rate is 250350 bpm; ventricular rate varies Rhythm: variable (depending on conduction) P-waves: saw-tooth appearance QRS: usually normal

D. Wandering Pacemaker      

Description: impulses originate from different foci in the atrium Rate: normal Rhythm: irregular P-waves:> 3 different forms PR interval: variable QRS: normal


E. Multifocal Atrial Tachycardia (MFAT)   

Rate: Fast; Irregular atrial rate (> 100) Rhythm: irregular P-wave: >3 different

forms  

PR interval: variable QRS: normal


Arrhythmia has such a fast rate that the P waves may not be seen Rate: 150-250 bpm Rhythm: regular P waves: frequently buried in preceding T waves QRS: normal, but may be wide if abnormally conducted through ventricles (aberrant conduction)

Atrioventricular Nodal Reentrant Tachycardia (AVNRT)  

Most common form of SVT Narrow QRS tachycardia with a short RP interval – P-waves buried in the QRS complex May have a “pseudo-S” wave (which is actually a retrogradely conducted P wave) in inferior leads or “pseudo-R prime” in V1


Wide QRS tachycardias (>120 ms or 3 small squares): usually ventricular in origin Differentials for wide QRS tachycardia o Ventricular tachycardia (VT): more common o Supraventricular tachycardia (SVT) with aberrancy  When faced with a wide-complex tachycardia and the morphology is in question, it is safer to treat as ventricular tachycardia (the more life-threatening differential) A. Premature Ventricular Contractions (PVC)  Prematurely occurring QRS complex which is wide and bizarre-looking  Usually no preceding Pwave  T wave opposite in Bigeminy: PVCs alternate with sinus beats deflection to the QRS



Trigeminy: PVC occurs after every 2 sinus beats

Couplet: two successive PVCs (if three successive PVCs, it is already considered unsustained VT)

B. Ventricular Tachycardia (VT) 1. VT According to Morphology a. Monomorphic Ventricular Tachycardia  Rapid, bizarre wide QRS complex (appearance of all the beats match each other in each lead)  No P-wave  Ventricular focus produces a rapid sequence of PVC-like wide ventricular complexes

b. Polymorphic Ventricular Tachycardia (Torsades de Pointes)  Beat-to-beat variations in appearance  Baseline rhythm demonstrates long QT interval  Presents with an oscillating pattern mimicking the “turning of the points” stitching pattern 2. VT According to Duration a. Sustained: ventricular tachycardia that lasts for more than 30 seconds b. Non-sustained: ventricular tachycardia that self-terminates within 30 seconds (presence of at least >3 successive PVCs is considered VT) 3. VT Based on Symptoms a. Pulseless VT: no effective cardiac output (no pulse, no BP)  defibrillate (treat as ventricular fibrillation) b. Unstable VT: with pulse, but unstable BP  cardioversion


C. Ventricular Fibrillation (VF)   

Associated with coarse or fine chaotic undulations No P-wave No true QRS complexes

PACEMAKER RHYTHM A. Ventricular Paced Rhythm   

RR interval is regular QRS complex is wide with an LBBB morphology Pacemaker spike (“blip”) is followed by a wide QRS complex (good capture)

B. Atrial Paced Rhythm  

Atrial pacing appears on the ECG as a single pacemaker stimulus followed by a P wave PR interval and configuration of the QRS complex are similar to those seen in a sinus rhythm

C. Dual Pacemaker (Atrial and Ventricular)



ISCHEMIA Findings suggestive of ischemia(should be in 2 or more contiguous leads)  ST segment depression > 1mm (> 1 small box)  Deep T-wave inversions > 5 mm (> 5 small boxes) 

For example, if there are ST segment depressions of >1mm in lead V5 and V6: then we can say that there is lateral wall ischemia. If ST segment depressions occur in V3 to V6: then we can say there is anterolateral wall ischemia.

The Contiguous Leads II, III, aVF I, aVL V1, V2 V3, V4 V5, V6 V1 – V3 V3 – V6, I, aVL V5, V6, II, III, aVF Almost all leads V3R, V4R (right-sided leads)

Inferior wall High lateral wall Septal wall Anterior wall Lateral wall Anteroseptal wall Anterolateral wall Inferolateral wall Diffuse, massive Right ventricular wall

INFARCTION A. Findings suggestive of injury or infarction Significant ST elevation:manifestation of myocardial necrosis; the earliest sign of acute infarction  > 1 mm ST elevation in contiguous limb leads, or  > 2 mm ST elevation in contiguous chest leads B. Pathologic Q-Waves    

Indicate myocardial necrosis Significant Q-wave: > 0.04 secs duration and > 25% of the R wave amplitude Ignored in lead V1 unless with abnormalities in other precordial leads Ignored in lead III unless with abnormalities in leads II and aVF

C. Classification as to Timing of Myocardial Infarction CLASSIFICATION (A) Normal (B) Acute MI (C) Recent MI (D) Old MI

TIMING Minutes to hours Hours to days Days to months

ECG FINDINGS ST elevation + peaked or inverted T-waves + Q waves Q-waves +ST elevation + T-wave inversion Q-waves + Isoelectric ST-segment + T-wave inversion

D. Posterior LV wall involvement   

Posterior wall ischemia, which is usually associated with lateral or inferior involvement, may be indirectly recognized by reciprocal or “mirror-image” ST depressions in leads V1 to V3 The posterior LV wall electrical activity is not represented in a typical standard surface ECG The anteroseptal leads (V1 to V3) are directed form the anterior precordium pointing towards the internal surface of the posterior myocardium

E. Reciprocal Changes  Pertains to ST-depression in leads opposite those demonstrating ST-elevation  “Ischemia at a distance”  Anterior MI: reciprocal change in inferior wall  Inferior MI: reciprocal change in I, aVL, or anterior wall  Lateral MI: reciprocal change in V1 or inferior wall



McGinn-White sign: S1Q3T3 pattern (large S-wave in lead I, Q-wave in lead III, and inverted T-wave in lead III) indicating acute right heart strain Sinus tachycardia: most commonly cited abnormality T wave inversion on leads V1-V4: another most commonly cited abnormality (due to RV strain) Right bundle branch block Low amplitude deflections


Beat to beat variation in the QRS amplitude Seen in massive pericardial effusion and/or cardiac tamponade







A. Left Bundle Branch Block (LBBB)

    

QRS duration >0.12 sec (complete LBBB) If 0.12 sec (complete RBBB) If 2mm, followed by a negative T-wave >2 mm J-point elevation, >1 mm ST-elevation and a saddleback appearance, followed by a positive or biphasic T-wave


DEXTROCARDIA (“Right Sided Heart”)    

Absent R-wave progression in the chest leads (dominant S-waves throughout) Predominantly negative P-wave, QRS complex, and T-wave in lead I Low voltage in leads V3-V6 (because these leads are placed on the left side of the chest) Accidental reversal of the left and right arm electrodes may produce a similar ECG pattern in the limb leads but with normal QRS morphology in the precordial leads


Non-specific ST-T wave changes

Poor R wave progression

Low voltage complexes

Electrolyte abnormalities

T-wave inversion, ST segment depression/elevation not fulfilling the criteria for ischemia or infarction (as outlined above): flattened or slightly inverted T-waves, ST segments slightly above or below the isoelectric line  R-wave in leads V1-V3 is < 3 small boxes  Normal R-wave in V4-V6  QRS complexes 10 mm, wide QRS, sine wave pattern Hypocalcemia  Prolonged QT interval Hypercalcemia  Shortened QT interval

CHEST RADIOGRAPH INTERPRETATION I. BASIC STEPS IN READING CHEST X-RAYS (CXR) Step 1: Identify general data Step 2: Determine view (PA, AP, lateral, decubitus) Step 3: Assess quality of film Step 4: Assess anatomy and determine abnormalities


STEP 1:    


Patient name Date/Time CXR was taken Diagnosis of patient Indication for CXR



Postero-Anterior View (PA) Scapula winged out, ribs and clavicles more angulated Arms at an angle with the body, with hands at waist Mongolian hat sign appreciated (formed by the C7 and T1 spinous + transverse processes) Heart not magnified

Antero-Posterior View (AP) Scapula not winged out; clavicles more horizontal Arms parallel to body Mongolian hat sign not appreciated Heart and other structures magnified

STEP 3: ASSESSING THE QUALITY OF THE FILM Inclusion Inspiratory Effort Exposure Obliquity

    

Apices of the lungs to the costophrenic angles should be adequately visualized One should count >8 intercostal spaces, 6-8 anterior ribs, 9-11 posterior ribs Upper four thoracic vertebrae should be visualized Medial ends of both clavicles equidistant from midline The spinous process of the thoracic vertebra should be in the midline

STEP 4: ASSESSING ANATOMY AND ABNORMALITIES A. General Structure  Soft tissues and bones: soft tissue swellings, rib fractures, breast shadow, osteopenia/osteoporosis  Trachea and mediastinum: carinal angle, tracheal position, mediastinal widening, masses  Vessels: aortic knob and pulmonary arteries  Diaphragm: right hemidiaphragm is usually higher than the left B. The Heart  Assess CT ratio: >0.50 in PA view suggests cardiomegaly  Cardiomegaly cannot be definitively ascertained on AP films, due to the possibility of magnification effects CHAMBER Left ventricular enlargement Right ventricular enlargement

Left atrial enlargement

      

Right atrial enlargement

PA FILM Apex displaced inferiorly and laterally (drooping apex) Apex displaced superiorly and laterally (uplifted apex) Prominence of left atrial appendage Loss of cardiac waistline Widening of carinal angle (>70o) Double density sign on right cardiac border Bulging right heart border (height >1/2 of right cardiac silhouette and width 1/3 of right hemithorax)

  

LATERAL FILM Obliteration of retrocardiac space Obliteration of retrosternal space Posterior displacement of the left mainstem bronchus on lateral film


C. The Lungs  CP angle: blunting suggests minimal pleural effusion  Pleura: check for pneumothorax, lesions  Parenchyma: check for opacities, densities, infiltrates  Lobes of the lungs:


o o

Right Lung (3 lobes): Right upper lobe (RUL) + right middle lobe (RML) + right lower lobe (RLL) Left lung (2 lobes): Left upper lobe (LUL) + lingula + left lower lobe (LLL)



Bronchiectasis Consolidation



                

Fungus Ball Hamartoma Pericardial Effusion

  

Pleural Effusion

          

Pneumomediastinum Pneumoperitoneum Pneumothorax

Pulmonary edema Pulmonary Metastasis

Mediastinum >30% of thoracic diameter, or mediastinum >8-10 cm Density in the area of the collapsed lung Displacement of interlobular fissures (direct sign) Surrounding structures deviated to the side of the collapsed lung (ipsilateral mediastinal shift) Crowding of vessels/bronchi Ipsilateral diaphragmatic elevation Appears as “bunches of grapes” (ring shadows) Tram-track lines Inhomogenous opacities Prominent air bronchogram sign Hyperaerated lungs Flattened hemidiaphragms Tubular heart Occasionally, bullae Decreased lung volume Shift of mediastinum and surrounding structures towards fibrotic area Blurred heart border or diaphragm with indistinct vascular markings in the areas of fibrosis Homogenous round opacity with a crescent sign Popcorn ball lesion Generalized enlargement of the cardiac shadow (“water bottle sign”) with normal vascular markings Blunting of costophrenic angles Meniscus sign Presence of gas between the mediastinal structures Presence of gas underneath the diaphragm Hyperlucent pulmonary area Loss of vascular markings beyond the visceral pleural line Mediastinal structures deviated to contralateral side (tension pneumothorax) Prominent hilar vessels (hilar fullness) in a bat-wing distribution Cephalization of vessels Kerley B lines Cannon ball lesions

ARTERIAL BLOOD GAS (ABG) INTERPRETATION I. BASIC STEPS IN ABG INTERPRETATION Step 1: Determine the primary acid-base disorder and whether compensation is appropriate Step 2: Check for secondary acid-base disorders Step 3: Compute for anion gap and / when needed Step 4: Check oxygenation status



Arterial pH pCO2 HCO3 Anion gap

NORMAL VALUES IN ARTERIAL BLOOD GAS 7.40 + 0.05 40 +2 24 + 2 12 + 2

B. Determine Primary Problem  To assess whether primary problem is respiratory or metabolic in origin, compare changes of HCO 3and pCO2 from baseline  If the change in HCO3 from baseline is larger, then the problem is primarily metabolic and vice versa Check pH

Check HCO3& pCO2 HCO3> CO2 CO2>HCO3 HCO3> CO2 CO2> HCO3

pH 7.4

PRIMARY DISTURBANCE Metabolic acidosis Respiratory acidosis Metabolic alkalosis Respiratory acidosis

C. Assess for appropriateness of compensation using the following formulas PRIMARY DISORDER Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis

COMPENSATION For every 1 meq/L FALL in HCO3,pCO2will DECREASE by 1.2 mmHg For every 1 meq/L RISE in HCO3,pCO2will INCREASE by 0.7 mmHg For every 10 mmHg RISE in pCO2, HCO3will INCREASE by 1 meq/L For every 10 mmHg FALL in pCO2, HCO3will DECREASE by 2 meq/L

STEP 2: CHECK FOR SECONDARY ACID-BASE DISORDERS A. In cases where there is inappropriate compensation, a secondary acid-base disorder should be considered PRIMARY DISORDER Metabolic Acidosis

Metabolic Alkalosis Respiratory Acidosis

Respiratory Alkalosis

COMPENSATION Actual reduction of pCO2 from baseline is HIGHER than that of calculated compensation Actual reduction of pCO2 from baseline is LESS than that of calculated compensation Actual increase of pCO2 from baseline is HIGHER than that of calculated compensation Actual increase of pCO2 from baseline is LESS than that of calculated compensation Actual increase of HCO3 from baseline is HIGHER than that of calculated compensation Actual increase of HCO3 baseline is LESS than that of calculated compensation Actual decrease of HCO3 from baseline is HIGHER than that of calculated compensation Actual decrease of HCO3 from baseline is LESS than that of calculated compensation



STEP 3: COMPUTE FOR ANION GAP AND A. Formula for Anion Gap



Anion gap = Na – (HCO3 + Cl)

 

Normal anion gap is 8-12 High anion gap is >12

B. Usual Causes of Metabolic Acidosis are as follows: HIGH-ANION GAP METABOLIC ACIDOSIS (HAGMA) P: Paraldehyde M: Methanol I: Isoniazid, Iron U: Uremia L: Lactic acidosis D: Diabetic ketoacidosis E: Ethylene glycol, Ethanol S: Salicylates

C. Check for

NORMAL ANION GAP METABOLIC ACIDOSIS (NAGMA) H: Hyperalimentation A: Acetazolamide R: Renal tubular acidosis D: Diarrhea U: Uretero-pelvic shunt P: Post-hypocapnia


1. For High-Anion Gap Metabolic Acidosis (HAGMA)

Anion Gap HCO3

  

If=1, there is pure HAGMA If 1, there is HAGMA + metabolic alkalosis

  

If=1, there is pure NAGMA If 1, there is NAGMA + metabolic alkalosis

2. For Normal-Anion Gap Metabolic Acidosis (NAGMA)

Chloride HCO3 D. Computing for Bicarbonate Deficit

HCO3 deficit = (desired HCO3– actual HCO3) x weight x 0.4 STEP 4: CHECK FOR OXYGENATION STATUS STATUS Hyperoxemia (more than adequate) Normoxemia Mild hypoxemia Moderate hypoxemia Severe hypoxemia

PO2 LEVEL ON ABG >100 mmHg 80-100 mmHg 60-79 mmHg 45-59 mmHg


THORACENTESIS MATERIALS                

Thoracentesis set Abbocath gauge #16 3 way stopcock Macroset/IV tubing Drapes 50cc syringe 10cc syringe Lidocaine 2% ampoules Clean (non-sterile) gloves Sterile gloves Cotton Rubbing alcohol Betadine Sterile gauze Micropore Sterile specimen vials/bottles

METHOD 1. Examine the patient and review available labs (CXR, CBC, blood chemistry,bleeding parameters) 2. Explain nature of procedure to patient and obtain consent 3. Extract simultaneous serum specimen for LDH, albumin, total protein and glucose 4. Position patient in sitting position with the mid-axillary line accessible for needle insertion 5. Confirm and mark topmost site of insertion by counting ribs based on CXR and percussing fluid level (usual site of insertion is at the 8th ICS posterior axillary line; alternatively, chest UTZ with markings can be done) 6. Observe sterile technique including sterile gloves, betadine prep and drapes 7. Anesthetize skin over insertion site with 2% Lidocaine, including superior surface of the rib and pleura 8. Insert thoracentesis needle perpendicularly through the anesthetized area to the same depth as the first needle and observe backflow of pleural fluid 9. Once with backflow, leave catheter in place, remove needle and attach three-way stopcock & tubing 10. Aspirate needed amount, then turn the stopcock and evacuate fluid through the tubing (do not remove more than 1.5L to avoid increased risk of re-expansionpulmonary edema or hypotension) 11. Fill specimen tubes/containers and label properly 12. When draining of fluid is complete, have patient take a deep breath or ask patient to cough and gently remove needle 13. Cover insertion site with sterile occlusive dressing 14. Send specimen for qualitative studies (pH, specific gravity, cell count and differentials, protein, LDH, albumin, glucose), gram stain and culture, AFB smear and additional studies as necessary (i.e., cytology for malignancy, amylase for pancreatitis, triglycerides for chylothorax) 15. Monitor patient closely and watch out for untoward reactions (chest pain, dyspnea, cough, infection) 16. Obtain upright CXR to evaluate lung expansion/fluid level and rule out pneumothorax 17. Provide post-procedural analgesics as necessary 18. Document procedure, patient response, side effects, nature of fluid drained and lab tests sent

PARACENTESIS MATERIALS              

Abbocath gauge #16 Macroset/IV tubing Drapes 50cc syringe 10cc syringe Lidocaine 2% ampoules Clean (non-sterile) gloves Sterile gloves Cotton Rubbing alcohol Betadine Sterile gauze Micropore Sterile specimen vials/ bottles

METHOD 1. Examine the patient and review available labs (CXR, CBC, blood chemistry,bleeding parameters) 2. Explain nature of procedure to patient and obtain consent 3. Have patient empty bladder prior to procedure 4. Extract simultaneous serum specimen for LDH, albumin, total protein and glucose 5. Assemble materials and prepare sterile field 6. Position patient in supine position with the trunk elevated 45 degrees 7. Confirm and mark the site of access (usually midline 3-4 cm below umbilicus, halfway between symphisis pubis and umbilicus) 8. Anesthetize skin over insertion site with 2% lidocaine, down to and including the peritoneum 9. Insert paracentesis needle perpendicularly through the anesthetized area to the same depth as the first needle and observe for backflow of fluid 10.Once with backflow, leave the catheter in place, remove needle and attach tubing draining into specimen needles 11.Remove the necessary amount of ascetic fluid 12. Monitor the patient for hypotension during the procedure 13. When draining of fluid is complete, remove needle and cover insertion site with sterile occlusive dressing 14. Fill specimen tubes/containers and label properly 15. Send specimens for qualitative studies (pH, specific gravity, cell count and differentials, LDH, protein, albumin, glucose), gram stain and culture, AFB smear and additional studies as necessary (i.e., cytology for malignancy) 16. Provide post-procedural analgesics as necessary 17. Document procedure, patient response, side effects, nature of fluid drained and lab tests sent



Foley catheter with urine bag Drapes 10cc syringe 1 vial syringe water Clean (non-sterile) gloves Sterile gloves Cotton Rubbing alcohol Betadine Lubricant (KY jelly) Micropore Sterile specimen bottles (if for urine collection)

METHOD 1. Hand hygiene 2. Prepare materials 3. Identify patient by name and introduce self to patient 4. Explain nature of procedure 5. Provide as much privacy as possible 6. Position patient properly 7. Wash and rinse urethral area 8. Open foley catheter package, put aside but maintain sterile zone around foley catheter 9. Wear clean gloves 10.Clean urethral opening aseptically: a. For male – in circular motions inside to out b. For female – follow a “7” figure then drop 11.Change to sterile gloves 12. Lubricate tip of catheter liberally 13. Attach drainage end of foley catheter to urine bag 14. Insert lubricated end of catheter into urinary meatus gently then push gently up until you are sure you are inside the bladder (usually up to the port where you inject water and there is urine backflow) 15. Observe for urine flow 16. Infuse 5-10ml of sterile water to inflate balloon 17. Pull foley catheter slowly until with some resistance 18. Secure foley catheter with tape 19. Dry patient’s perineum 20. Instruct patient on catheter care 21. Remove gloves 22. Hand hygiene


IV cathula Macroset/IV tubing Clean (non-sterile) gloves Tourniquet Cotton Rubbing alcohol Micropore Splint (optional)

METHOD 1. Hand hygiene 2. Prepare materials 3. Identify patient by name and introduce self to patient 4. Explain nature of procedure 5. Wear clean gloves 6. Select position/site of venipuncture 7. Swab puncture site with alcohol on concentric circles inside to out 8. Apply tourniquet 9. Stabilize the selected site 10.Insert needle bevel up 11.Observe for blood backflow 12. Remove needle while pushing cathula further into the vein 13. Attach infusion set quickly while pressing on vein to prevent excessive escape of blood 14. Release tourniquet 15. Try running the IV line to check that fluid infuses continuously and there is no bulging at the insertion site 16. Cover the insertion site with a 1x1 sterile gauze and tape securely 17. Loop tubing and secure with tape 18. Apply splint 19. Instruct the patient on care of IV site 20. Discard sharps properly 21. Remove gloves 22. Hand hygiene








120-180g/L 12.0-18.0 g/dL


150-450 x 109/L 150-450 x 103/mm3


4-11 x 109/L 4-11 x 103/mm3 Hematocrit:





MCV MCH MCHC RDW-CV Reticulocytes

4-6 x 1012/L (106/mm3) 80-100 fL 27-31 pg 320-360 g/L 11-16% 0.005-0.015





Glucose BUN Creatinine Sodium Potassium Chloride Calcium Magnesium Phosphorus Total protein Albumin Globulin AST (SGOT) ALT (SGPT) Alkaline phosphatase

Total bilirubin Direct bilirubin Indirect bilirubin

Uric acid Ammonia Amylase



3.9-6.1 mmol/L 2.6-6.4 mmol/L 53-115 umol/L 136-146 mmol/L 3.5-5.2 mmol/L 100-108 mmol/L 2.12-2.52 mmol/L 0.70-1.00 mmol/L 0.81-1.4 mmol/L 64-83 g/L 34-50 g/L 23-35 g/L 15-37 U/L 30-65 U/L 36-92 umol/L

75-100 mg/dL 7-20 mg/dL 0.6-1.3 ng/mL 136-146 mEq/L

0-17.1 umol/L 0-5.00 umol/L 3.4-13.7 umol/L 0.13-0.44 umol/L 11-35 umol/L 0.34-1.6 ukat/L

0.3-1.3 mg/dL 0.1-0.4 mg/dL 0.2-0.9 mg/dL 3.1-7.0 mg/dL

3.5-5.2 mEq/L 100-108 mEq/L 8.7-10.2 mg/dL


Lipase LDH CRP RF Free T4 Free T3 TSH

1.5-2.3 mg/dL 2.5-4.3 mg/dL 6.4-8.3 g/dL 3.4-5.0 g/dL 2.3-3.5 g/dL 15-37 U/L 30-65 U/L 36-92 umol/L

PSA < 40 y/o PSA > 40 y/o AFP CA 125 CA 19-9 CEA (nonsmokers) CEA (smokers) CK-total CK MB CK MM Troponin I



0.51-0.73 ukat/L 2.0-3.8 ukat/L 0.2-3.0 mg/L < 30 kIU/L 10.3-21.9 pmol/L 3.7-6.5 pmol/L 0.34-4.25 mIU/L 0.0-2.0 ug/L 0.0-4.0 ug/L 0.0-8.5 ug/L 0-35 kU/L 0-37 kU/L 0-3.0 ug/L

23-300 U/L

2.4-4.2 pg/mL 0.34-4.25 uIU/mL 0.0-2.0 ng/mL 0.0-4.0 ng/mL 0.0-8.5 ng/mL 0-35 U/mL 0-37 U/mL 0-3.0 ng/mL

0-5.0 ug/L

0-5.0 ng/mL

55-170 U/L 0-16 U/L 8-97 U/L 0-0.09 ng/mL

55-170 U/L 0-16 U/L 8-97 U/L 0-0.09 ug/L

100-190 U/L 0.2-3.0 mg/L < 30 kIU/mL 0.8-1.7 ng/dL

19-60 ug/dL 30-110 U/L



Color Specific gravity pH Sugar, Albumin RBC WBC Casts Crystals Epithelial cells Bacteria Mucus thread


Yellow, clear/hazy 1.016-1.022 4.6-6.5 (-) 0 / 0-2 / hpf 0-2 / 0-5 / hpf Hyaline, coarse, fine, granular, waxy Small amounts Small amounts (-) Small amounts

Total volume Creatinine Total protein Na+ K+ ClUric acid CA2+ Phosphorus Amylase Mucus thread Microalbumin

500-2000cc 0.65-0.70 g/L or 8.8-14 mmol/d 0-0.1 g/24hr or < 100 mg/d 80-260 mmol/L 25-100 mmol/L 80-340 mmol/L 4.42-5.9 mmol/24hr 2.5-7.5 mmol/24hr 22.4-33.6 mmol/24hr 64.75-490.25 U/L Small amounts N: 0.0-0.03 g/d Microalbuminuria: 0.03-0.30 g/d Clinical albuminuria: >0.3 g/d

EQUIVALENT VALUES To convert to mg/dL PARAMETER RBS (mmol/L) BUN (mmol/L) Creatinine (umol/L) Calcium (mmol/L) Magnesium (mmol/L) Bilirubin (umol/L) Uric acid (umol/L) HDL or LDL (mmol/L) Triglycerides (mmol/L)

Equivalent values of common interventions FACTOR Multiply by 18 Multiply by 2.8 Divide by 88.4 Divide by 0.25 Divide by 0.411 Divide by 17.10 Divide by 59.48 Divide by 0.0259 Divide by 0.0113

INTERVENTION 1 cc 10% oral KCl 15 cc 10% oral KCl 30 cc 10% oral KCl Kaliumdurule (750mg) 1 medium sized banana NaHCO3 50mL NaHCO3GrX tab (650 mg) NaCl tab (1g) Normal saline solution (1L)

EQUIVALENT 1.33 meqs K+ 20 meqs K+ 40 meqs K+ 10 meqs K+ Roughly 7-10 meqs K+ 45 meqs Na+ 7.7 meqs Na+per tab 17 meqs Na+ per tab 154 meqs Na+per liter




Blood products

DESCRIPTIONS Balanced salt / electrolyte solutions which may be isotonic, hypertonic or hypotonic High-molecular weight solutions which draw fluid into the intravascular component via oncotic pressure Effective plasma expanders Provide water that is not bound by macromolecules or organelles, thus is free to pass through membranes Essentially are also considered colloids

EXAMPLES Normal saline (0.9% NaCl), lactated Ringer’s, hypertonic saline (3, 5, 7.5%), Ringer’s solution

Albumin, hetastarch, plasma and dextran

D5W (5% dextrose in water), D10W, D20W, D50W, D50-50, dextrose/ crystalloid mixes Whole blood, pRBC, FFP, cryoprecipitate, platelet concentrate








HCO3 


50 gm/L

D10W 0.9 NSS

100 gm/L

D5 0.9 NSS

50 gm/L


    





130 140

109 98

4 5



  


50 gm/L





50 gm/L




COMMENTS Useful in dehydrated states and hypernatremia Can be used as diluents Used to correct hypoglycemia Fluid of choice for initial resuscitation Can be used as diluents Same as 0.9 NSS but with additional glucose Useful for patients on NPO Useful for trauma, surgery and burn patients Routine fluid and electrolyte maintenance with minimal carbohydrate calories Same as D5NM but with additional potassium content


  

Maintain normal blood pressure: normal or isotonic saline is the initial fluid of choice Return the intracellular (ICF) volume to normal o In patients with acute hyponatremia, the ICF volume in the brain rises and could become dangerous high with more prominent decline in plasma sodium  hypertonic saline usually given to raise the plasma sodium o When there is a large water deficit in the ICF compartment (e.g. severe hypernatremia), electrolyte-free water (D5W) is given Replace ongoing renal losses Give maintenance fluids to match insensible losses Provide glucose as fuel substrate for the brain, thereby useful for patients on NPO (dextrose-containing fluids)


IV. COMMONLY USED INTRAVENOUS FLUIDS 1. Normal Saline (0,9% NaCl, pNSS)  Least expensive and most commonly used resuscitative crystalloid  High Cl content imposes on the kidneys an excess Cl load that cannot be rapidly excreted  risk of hyperchloremic acidosis  The only solution that may be administered with blood products  Does not provide free water or calories 2. Lactated Ringer’s (LR) Solution  Lactate is converted readily to bicarbonate in the liver  Minimal effects on normal body fluid composition and pH  Most closely resembles the electrolyte composition of normal blood serum  Does not provide calories 3. D5W or ¼ Normal Saline  Provides 170 calories/L from 5% dextrose  Provides free water for insensible losses and some sodium to promote renal function and excretion  With added potassium, this is an excellent maintenance fluid in the immediate postoperative period  Prevents excess catabolism and limits proteolysis 4. Hypertonic Saline (3% NaCl)  1026 mOsm/L, 513 mEq/L Na+  Increases plasma osmolality and thereby acts as a plasma expander, increasing circulatory volume via movement of intracellular and interstitial water into the intravascular space  Due to high sodium content, poses high risk of hypernatremia

Before proceeding to the next section, here are some general terminologies using drips:


equal to

ugtt/min (microdrops/min)


divided by 4

Infusion rate (cc / hr) =

equal to



gtt/min (drops/min)

dose (mcg / kg / min) x BW in kg x 60 min solution concentration (mcg / cc)

solution concentration (mcg / cc) =

dose of drug (mcg)_ volume of diluent (cc)




Generally used to augment BP and cardiac output in patients with cardiogenic shock Dopamine releases norepinephrine from nerve terminals, which itself stimulates A1 and B1 receptors Usually started at an infusion rate of 2-5 mcg/kg/min Dose is increased every 2-5 minutes to a maximum of 20-50 mcg/kg/min

A. Things to know about Dopamine:  

Preparation Sample order

  Dopamine factor

One ampule contains 200 mg dopamine Dopamine drip: 200mg dopamine (1 ampule) + 250 cc D5W to run for ____ cc/hr For a formulation of 1 ampule (200mg) in 250 cc D5W factor, used is 13.3 For a formulation of 2 ampules (400mg) in 250 cc D 5W factor, used is 26.6

NOTE: A more concentrated dose is usually chosen for patients who cannot tolerate fluid overload (e.g. patients with CHF, CKD) B. Dopamine demonstrates varying Hemodynamic Effects based on the dose DOSE



< 2 mcg/kg/min

Activates DA1 and DA2 receptors

Renal Vasodilation: Vasodilation of splanchnic and renal vasculature

2-10 mcg/kg/min

Activates B1-receptors

> 10 mcg/kg/min

Effects on A1-receptors overwhelm the dopaminergic receptors

Inotropic: Increase in cardiac output with little or no change in HR or SVR Vasoconstrictor: Vasoconstriction, leading to increase in SVR, LV filling pressures, and HR

Source: Fauci,, Harrison’s Principles of Internal Medicine 19th edition, 2015.

C. Computation of Dopamine Drip Rate based on Desired Dose

Desired dose Dopamine drip rate (ugtt/min) =

mcg kg min x Body Weight (kg) Dopamine factor

D. Sample computation  

55/F patient, 45kg, admitted for cardiogenic shock with BP of 80/50 mmHg If our desired dose is 10mcg/kg/min (chronotropic/inotropic dose) and we decide to give 400mg (2 amps) dopamine (factor is 26.6), the dopamine rate is computed as follows:

mcg Dopamine drip rate (ugtt/min) =10

kg min x 45 (kg) = 16.9 = 17 cc/hr = 17 ugtt/min 26.6

Sample chart order:


 Start dopamine drip: 400mg (2amps dopamine) + 250cc D5W x 17 cc/hr (dose of ~10 mcg/kg/min)  Titrate by 2-3 cc/hr to maintain BP > 90/60 E. Reverse computation: computing for the DOSE of dopamine being administered  Note that when reporting/endorsing a case, it is better to state the dose of dopamine that the patient is being given and not the drip rate. To compute for the specific dose, use the following formula

Dopamine dose

mcg min kg


Dopamine drip rate ugtt x Dopamine factor min________________ body weight (kg)

Example: Patient is a 45-kg, 55/F, given 2 amps of Dopamine (200 mg/amp) in 250cc PNSS at a rate of 19 ugtts/min (or 19cc/hr). QUESTION: What is the dose of dopamine being given to the patient?

Dose given (in mcg/kg/min) = rate (in ugtt/min) x 26.6 = 19ugtt/min x 26.6 = 11.23mcg/kg.min

45 kg

45 kg

Answer: 11.23 mcg/kg/min is the dose being given to the patient at a rate of 19 ugtts/min (or 19cc/hr). Since we are giving 11.23 mcg/kg/min, we have a vasoconstricting effect which is beneficial in a patient with septic shock. If the patient is still hypotensive, we can increase the ugtt/min (titrate) up 34 ugtt/min (20mcg/kg/min) for a 45-kg patient (“dopa max”). If still with no response to maximal dopamine dosing, we can start another inotrope like norepinephrine. In the computation, we used 26.6 because 2 ampules of dopamine were used for the patient. F. For quick reference: 1. Dopamine 200 mg + 250 cc D5W preparation

Drip Rate (ugtt/min or cc/hr) 2.5 Dose 5.0 (mcg/ 7.5 kg/min) 10.0 15.0 20.0

Body Weight in Kg 40 kg

50 kg

60 kg

70 kg

80 kg

90 kg

7.5 cc/hr 15.0 cc/hr 22.5 cc/hr 30.0 cc/hr 45.0 cc/hr 60.0 cc/hr

9.4 cc/hr 18.8 cc/hr 28.1 cc/hr 37.5 cc/hr 56.3 cc/hr 75.0 cc/hr

11.3 cc/hr 22.5 cc/hr 33.8 cc/hr 45.0 cc/hr 67.5 cc/hr 90.0 cc/hr

13.1 cc/hr 26.3 cc/hr 39.4 cc/hr 52.5 cc/hr 78.8 cc/hr 105.0 cc/hr

15.0 cc/hr 30.0 cc/hr 45.0 cc/hr 60.0 cc/hr 90.0 cc/hr 120.0 cc/hr

16.9 cc/hr 33.8 cc/hr 50.6 cc/hr 67.5 cc/hr 101.3 cc/hr 135.0 cc/hr

2. Dopamine 400 mg + 250 cc D5W Preparation Drip Rate (ugtt/min or cc/hr) 2.5 Dose 5.0 (mcg/ 7.5 kg/min) 10.0 15.0 20.0

Body Weight in Kg 40 kg

50 kg

60 kg

70 kg

80 kg

90 kg

3.8 cc/hr 7.5 cc/hr 11.3 cc/hr 15.0 cc/hr 22.5 cc/hr 30.0 cc/hr

4.7 cc/hr 9.4 cc/hr 14.1 cc/hr 18.8 cc/hr 28.1 cc/hr 37.5 cc/hr

5.6 cc/hr 11.3 cc/hr 16.9 cc/hr 22.5 cc/hr 33.8 cc/hr 45.0 cc/hr

6.6 cc/hr 13.1 cc/hr 19.7 cc/hr 26.3 cc/hr 39.4 cc/hr 52.5 cc/hr

7.5 cc/hr 15.0 cc/hr 22.5 cc/hr 30.0 cc/hr 45.0 cc/hr 60.0 cc/hr

8.4 cc/hr 16.9 cc/hr 25.3 cc/hr 33.8 cc/hr 50.6 cc/hr 67.5 cc/hr


II. DOBUTAMINE  A synthetic sympathomimetic amine with positive inotropic action  Effects are due to selective stimulation of B1 adrenergic receptors A. Things to know about Dobutamine: Preparation Sample order

   

Dobutamine factor

One ampule contains 250 mg dobutamine Dobutamine drip: 250mg dobutamine (1 amp) + 250 cc D5W to run for ___ cc/hr For a formulation of 1 ampule (250 mg) in 250 cc D 5W, factor used is 16.6 For a formulation of 2 ampules (500 mg) in 250 cc D5W,factor used is 33.2

NOTE: A more complicated dose is usually chosen for patients who cannot tolerate fluid overload (e.g. patients with CHF, CKD) B. Effects of Dobutamine (dose-dependent)  Minimal positive chronotropic activity at low doses(2.5 mcg/kg/min) and moderate chronotropic activity at higher doses  Usually given at 10 mcg/kg/min, however, its vasodilatory effect at this dose precludes its use in patients with decreased systemic vascular resistance C. Computation of Dobutamine Drip Rate based on Desired Dose

Dobutamine Drip Rate (ugtt/min) =

Desired dose mcg min x Body weight (kg) kg_____________________ Dobutamine factor

D. Sample computation  60/M patient, 50 kg, in cardiogenic shock from decompensated heart failure with BP of 80/50 mmHg  If our desired dose is 5 mcg/kg/min and we decide to use 500 mg (2 amps) dobutamine (factor is 33.2)

5 Dobutamine Drip Rate (ugtt/min) =

mcg min x 50 (kg) kg_______________ = 7.5 = 8cc/hr = 8 ugtt/min 33.2

Sample chart order:  Start dobutamine drip: 500 mg (2 amps dobutamine) + 250 cc D5W x 8 cc/hr (dose of 5 mcg/kg/min)  Titrate by 2-3 cc/hr to maintain BP >90/60 until 15 cc/hr (~10 mcg/kg/min)   

The maximum dose of 15 cc/hr was computed using the dose 10 mcg/kg/min Note that when endorsing a case, it is better to state the dose of dobutamine that the patient is being given and not the drip rate To compute for the specific dose, use the following formula

Dobutamine drip rate ugtt x Dobutamine factor Dobutamine Dose mcg min = min_____________________ kg body weight (kg)


E. For quick reference: 1. Dobutamine 250 mg + 250 cc D5W Preparation Drip Rate (ugtt/min or cc/hr) 2.5 Dose 5.0 (mcg/ 7.5 kg/min) 10.0 15.0 20.0

Body Weight in Kg 40 kg

50 kg

60 kg

70 kg

80 kg

90 kg

6.0 cc/hr 12.0 cc/hr 18.0 cc/hr 24.0 cc/hr 36.0 cc/hr 48.0 cc/hr

7.5 cc/hr 15.0 cc/hr 22.5 cc/hr 30.0 cc/hr 45.0 cc/hr 60.0 cc/hr

9.0 cc/hr 18.0 cc/hr 27.0 cc/hr 36.0 cc/hr 54.0 cc/hr 72.0 cc/hr

10.5 cc/hr 21.0 cc/hr 31.5 cc/hr 42.0 cc/hr 63.0 cc/hr 84.0 cc/hr

12.0 cc/hr 24.0 cc/hr 36.0 cc/hr 48.0 cc/hr 72.0 cc/hr 96.0 cc/hr

13.5 cc/hr 27.0 cc/hr 40.5 cc/hr 54.0 cc/hr 81.0 cc/hr 108.0 cc/hr

2. Dobutamine 500 mg + 250 cc D5W Preparation Drip Rate (ugtt/min or cc/hr) 2.5 Dose 5.0 (mcg/ 7.5 kg/min) 10.0 15.0 20.0

Body Weight in Kg 40 kg

50 kg

60 kg

70 kg

80 kg

90 kg

3.0 cc/hr 6.0 cc/hr 9.0 cc/hr 12.0 cc/hr 18.0 cc/hr 24.0 cc/hr

3.8 cc/hr 7.5 cc/hr 11.3 cc/hr 15.0 cc/hr 22.5 cc/hr 30.0 cc/hr

4.5 cc/hr 9.0 cc/hr 13.5 cc/hr 18.0 cc/hr 27.0 cc/hr 36.0 cc/hr

5.3 cc/hr 10.5 cc/hr 15.8 cc/hr 21.0 cc/hr 31.5 cc/hr 42.0 cc/hr

6.0 cc/hr 12.0 cc/hr 18.0 cc/hr 24.0 cc/hr 36.0 cc/hr 48.0 cc/hr

6.8 cc/hr 13.5 cc/hr 20.3 cc/hr 27.0 cc/hr 40.5 cc/hr 54.0 cc/hr

III. NORADRENALINE/NOREPINEPHRINE  A potent vasoconstrictor and inotropic stimulant  Despite non-significant improvement in survival compared to patients given dopamine, the relatively safer profile of norepinephrine makes it a good initial vasopressor therapy  Usually started at a dose of 2 to 4 mcg/minand titrated upward as necessary  If systematic perfusion or systolic pressure cannot be maintained at >90 mmHg with a dose of 15 mcg/min, it is unlikely that a further increase in dose will be beneficial A. METHOD 1: Long Method Step 1: Compute for concentration EXAMPLE: For 4 mg norepinephrine + 250 cc D5W

Concentration =

stock (mg) x 1000 mcg 250 cc IVF 1 mg Concentration =

4 mg x 1000 mcg 250 cc 1 mg

Step 2: Compute for infusion rate mcg / min Infusion rate cc = dose kg x weight (kg) x 60 min/hr hr concentration (mcg/cc) Sample chart order:  To start norepinephrine drip as follows: 4 mg norepinephrine + 250 D 5W x 38 cc/hr (0.2 mcg/kg/min or 10 mcg/min in a 50 kg patient)  Titrate by 5 cc/hr to maintain BP >90/60


To compute for the current dose given a certain infusion rate, use the following formula:


mcg / min =Infusion rate (cc/hr) x concentration (mcg/cc) kg weight (kg) 60 min/hr

B. METHOD 2: Short-Cut Method Computation for Norepinephrine Drip Rate based on Desired Dose

Desired dose (mcg/min)____ Norepinephrine Drip Rate (ugtt/min) =

Norepinephrine factor

Norepinephrine Factor  Norepinephrine drip: 2 mg (1 amp) + 250cc D5W (factor used: 0.133)  Norepinephrine drip: 4 mg (2 amps) + 250cc D5W (factor used: 0.266)  Norepinephrine drip: 8 mg (4 amps) + 250cc D5W (factor used: 0.532) *A more concentrated dose is usually chosen for patients who cannot tolerate fluid overload

C. For quick reference: Drip rate (ugtt/min or cc/hr) 5 cc/hr 10 cc/hr 15 cc/hr 20 cc/hr 25 cc/hr 30 cc/hr 40 cc/hr 50 cc/hr 60 cc/hr 70 cc/hr 80 cc/hr 90 cc/hr 100 cc/hr

Dose (mcg/min) Norepinephrine 2mg + 250 cc D5W Norepinephrine 4mg + 250 cc D5W Preparation Preparation 0.7 mcg/min 1.3 mcg/min 1.4 mcg/min 2.7 mcg/min 2.0 mcg/min 4.0 mcg/min 2.7 mcg/min 5.3 mcg/min 3.4 mcg/min 6.7 mcg/min 4.0 mcg/min 8.0 mcg/min 5.5 mcg/min 10.7 mcg/min 6.7 mcg/min 13.3 mcg/min 8.0 mcg/min 16.0 mcg/min 9.4 mcg/min 18.7 mcg/min 10.7 mcg/min 21.3 mcg/min 12.0 mcg/min 24.0 mcg/min 13.4 mcg/min 26.7 mcg/min

IV. UNFRACTIONED HEPARIN (UFH)  A sulfated polysaccharide usually isolated from mammalian tissues rich in mast cells  Acts as an anticoagulant by activating antithrombin (AT III) and accelerating the rate at which antithrombin inhibits clotting enzymes, particularly thrombin and factor Xa A. Usual Formulation of Heparin Drip  Heparin drip: 10,000 units of UFH in enough pNSS to make 100 cc in a soluset (concentration of 10,000 units/100 cc or 100 units/cc) B. Usual doses for Common Indications Myocardial infarction = “60-12” 60 units/kg IV push as loading dose then start IV drip at 12 units/kg/hr Deep vein thrombosis or 80 units/kg IV push as loading does then start IV drip at 18 units/kg/hr pulmonary embolism = ’80-18”


C. Heparin Drip Adjustment:  PTT is ideally monitored every 6 hours (after a dose change) and IV drip adjusted accordingly to reach target PTT of 1.5-2.5 times the control (46-70 sec) 

Raschke’s Protocol aPTT 3.0x control

Mayo Clinic Protocol aPTT (seconds) 90

Heparin Adjustment 80 u/kg IV bolus then add 4 u/kg/hr to infusion rate 40 u/kg IV bolus then add 2 u/kg/hr to infusion rate No change Decrease infusion rate by 2 u/kg/hr Discontinue for 1 hour, then decrease infusion rate by 2 u/kg/hr

Heparin Adjustment 80 u/kg bolus then increase drip rate by 4 u/kg/hr 40 u/kg bolus then increase drip rate by 2 u/kg/hr No change Reduce drip rate by 2 u/kg/hr Withhold heparin for 1 hour then reduce drip rate by 3 u/kg/hr

*Order a PTT 6 hours after any dosage change and adjust accordingly until PTT is therapeutic (~46-70). When two consecutive PTTs are therapeutic, order PTT every 24 hours

V. INSULIN DRIP (Insulin regimen would depend on the indication) A. For Hyperkalemia  Insulin causes K+ shift (extracellular potassium goes intracellularly)  Glucose-Insulin (GI) solution: 50 mL of 50% Dextrose in Water (D50-50) + 10 units Regular Insulin in 2-5 minutes  Sample order: Mix 1 amp D50-50 + 10 units Humulin-R IV stat, then q6h x 4 doses B. For Hyperglycemia 1. Formulation of Insulin drip (depends on physician)  Example (drip 1) 20 units of Insulin (HR) in 100cc pNSS = concentration of 0.2unit/cc (20units/100cc)  Example (drip 2) 50 units of Insulin (HR) in 100cc pNSS = concentration of 0.5unit/cc (50units/100cc)  Example (drip 3) 100 units of Insulin (HR) in 100cc pNSS = concentration of 1unit/cc (100units/100cc) 2. Examples Example 1: If we decide to give our patient 2 units of insulin per hour (via insulin drip):  For drip 1: give 10 cc per hour (10 cc/hr or 10 gtts/min)  For drip 2: give 4 cc per hour (4 cc/hr or 4 ugtts/min)  For drip 3: give 2 cc per hour (2 cc/hr or 2 ugtts/min) Example 2: Start drip at 0.1 unit/kg/hr, titrate to desired blood glucose  If the patient is 50kg, start Insulin drip at 5 units/hr. if we decide to use drip #3 form the example above, the order will be: Insulin drip 100 units HR + 100 cc pNSS at a rate of 5 cc/hr (to deliver 5 units/hr) V. NICARDIPINE  An intravenous calcium channel blocker used as a first-line agent in the management of hypertensive crises A. Things to know about Nicardipine: Preparation One 10 mL ampule contains 10 mg Nicardipine Drip: 10 mg Nicardipine + 90 mL D5W or pNSS in soluset Usual formulation Concentration: 0.1 mg/mL of Nicardipine Dose Initial dose 5 mg/hr (ex. HPN emergency)


5mg/hr = 50 cc/hr (pr 50 ugtt/min) 0.1 mg/cc


Some would give an initial IV bolus prior to starting drip Titrate by 2,5 mg/hr q15 minutes until target BP is reached Maximum dose: 15 mg/hr

B. Sample chart order:  Start Nicardipine drip as follows: 10 mg Nicardipine + 90 cc D5W in a soluset x 50 cc/hr, titrate by 2.5 mg/hr every 15 minutes until target BP is reached

VI. NITROGLYCERIN (GLYCERYL TRINITRATE)  Organic nitrate which causes systemic venodilation, decreasing preload and afterload and reducing myocardial oxygen demand  Also improves coronary collateral circulation A. Things to know about Nitroglycerin Preparation One ampule contains 10 mg nitroglycerin Drip: 10 mg + 90 cc D5W in soluset Usual formulation Concentration: 0.1 mg/cc of NTG 100 mcg/cc of NTG Initial dose 5 mcg/min or 300 mcg/hr Dose 300 mcg/hr = 3 cc/hr (or 4 uggt/min) 100 mcg/cc Titration Titrate by 5 mcg.min q5min until pain relief is achieved or BP is controlled B. Sample chart order:  Start nitroglycerin drip: 10mg nitroglycerin + 90cc D5W in a soluset x 3cc/hr, titrate by 3 cc/hr until chest pain-free


OTHER COMMONLY USED DRIPS DRUG NAME Amiodarone (Antiarrhythmic, Class III)

 Bumetanide (Loop diuretic)

  

Furosemide (Loop diuretic)

 

Dexmedetomedine (A2-Agonist)

Esmolol (Beta blocker)

IsosorbideDinitrate (Nitrate)

DOSE Continuous infusion: 1 mg/min for 6hrs, then 0.5 mg/min infusion Bolus: 0.5-1 mg SIVP over 1-2 min Continuous infusion: 1 mg/hr (usually 1 mg/hr or higher) Bolus: 2-40 mg SIVP x 1-2 min Continuous infusion: 110mg/hr Loading dose: 1 mcg/kg x 10min Continuous infusion: 0.20.7 mcg/kg/hr Continuous infusion: 50200 mcg/kg/min

PREPARATION Bolus: 150 mg SIVP then drip: 150-600 mg + 250 cc D5W x 16-24 hours

Drip: 1 mg + 10 mL NSS or D5W

Depends on diuretic response and fluid status

Drip: 100 mg + 100 mL diluents

Depends on diuretic response and fluid status

Drip: 2 mL of dexmedetomidine + 48 mL of 0.9 pNSS (total of 50 mL) Drip: 2500 mg + 250 mL diluents

Titrate in 0.1 mcg/kg/hr increments to desired level of sedation (max dose: 1.5 mcg/kg/hr) Titrate in 50 mcg/kg/min increments every four minutes May titrate by 1 mg every 15-30 mins until chest pain-free (as long as patient’s BP is normal) Rate of infusion should be reassessed as soon as basic rhythm appears to be stable or at the earliest signs of toxicity. It is rarely necessary to continue IV lidocaine for prolonged periods Increase rate by 1 mg/hr based on sedation (titrate to lowest dose possible) Depends on type of sedation used

 

Continuous infusion: 1-5 mg/hr

Drip: 10 mg + 90 mL diluents 

Lidocaine (Anti-arrhthymic)

Continuous infusion: 1-4 mg/min

Drip: 1-2 grams + 500 mL diluents (NSS or D5W)

Midazolam (Benzodiazepine)

Continuous infusion: 1-30 mg/min

Drip: 125 mg + 125 mL diluents

Morphine (Opioid)

 

Drip: 16 mg + 50 cc diluent

Omeprazole (PPI)

  

Somatostatin (Splanchnic vasoconstrictor)

 

Bolus: 80 mg IV then drip: 40 mg + 90 cc pNSS x 5 hours RTC Drip: 60-90 mg in 250 cc pNSS x 2-24 hours Drip: 3 mg + 250 mL D5W x 12 hours

Pamidronate (Biphosphonate)

Bolus: 2-4 mg SIVP Continuous infusion: 1-2 mg/hr Bolus: 40-80 mg IV Continuous infusion: 8 mg/hr Continuous infusion: 60-90 mg IV infusion over 2-24hrs

Bolus: 250 mcg IV Continuous infusion: 250 mcg/hr

HOW TO TITRATE Goal is to load 1 g of amiodarone within 24 hours

 

Maintain the drip rate continuously for 72 hours Single dose usually given every 3-4 weeks Maintain drip continuously for hours

rate 72


CHAPTER 2 CARDIOLOGY I. Introduction to Cardiology II. Approach to Patients with Cardiovascular Conditions 1. 2. 3.

Cardiovascular History Cardiovascular Physical Examination The Cardiac Diagnosis

III. Common Conditions in Cardiology 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13.

Atherosclerosis and Dyslipidemia Hypertension Heart failure Chronic Stable Angina Pectoris Acute Coronary Syndrome A. Non-ST Elevation Acute Coronary Syndrome B. ST-elevation Myocardial Infarction Rheumatic Fever Valvular Heart Disease Pericarditis Cardiac tamponade Cardiomyopathy Atrial Fibrillation Peripheral Artery Disease CorPulmonale 37






STROKE VOLUME (SV)  Volume of blood pumped with each heart beat  Normal range is 55-100mL (for a 70kg man, normal is ~70mL)  SV = stroke volume (mL/beat)  EDV = end diastolic volume (N: 65-240 mL)  ESV = end systolic volume (N: 16-143 mL) EJECTION FRACTION (EF)  Most useful index of LV function  Fraction of blood ejected by the LV during systole  EF = ejection fraction CARDIAC OUTPUT (CO)  Volume of blood being pumped by the heart per minute  Normal CO = 5.0 – 5.5 L/min  CO = cardiac output (L/min)  HR = heart rate (bpm) BLOOD PRESSURE (BP) 


SVR = systematic vascular resistance (resistance to blood flow through vascular system)


BSA = Weight (kg) x Height (cm) 3600



 

Better indicator of metabolic mass than body weight BSA = body surface area (m 2)

CARDIAC INDEX (CI)  Marker of cardiac function in relation to BSA, thus relating heart performance to the size of the individual  Normal CI = 2.6 – 4.2 L/min/m2  If CI < 1.8 L/min/m2 suspect cardiogenic shock MEAN ARTERIAL PRESSURE (MAP)  Defined as the average arterial pressure during a single cardiac cycle  SBP = systolic blood pressure in mmHg  DBP = diastolic blood pressure in mmHg  Normal MAP = > 60mmHg  can sustain organ perfusion (normally 70-110 mmHg)


 

PULSE PRESSURE (PP)  Represents the force that the heart generates each time it contracts PP = SP – DP  PP = pulse pressure: usually about 30-40 mmHg  SP = systolic pressure (mmHg)  DP = diastolic pressure (mmHg) Normal PP: if PP < 25% of the systolic value (eg, Low stroke volume, blood loss, aortic stenosis, tamponade) Wide PP: may reach up to 100mmHg (eg., exercise, atherosclerosis, aortic regurgitation, AV malformation, hyperthyroidism, aortic dilatation / aneurysm, fever, anemia, pregnancy, anxiety, beri-beri)

Maximum HR = 220 – Age

Target HR = Maximum HR x

MAXIMUM HEART RATE  Highest HR an individual can achieve without severe problems through exercise-induced stress

TARGET HEART RATE  A specific age-based pulse rate to be maintained 0.85 during aerobic exercise to ensure optimal cardiovascular function



APPROACH TO PATIENTS WITH CARDIOVASCULAR CONDITIONS CARDIOVASCULAR HISTORY I. CARDINAL SYMPTOMS OF CARDIOVASCULAR DISEASE  Chest pain or discomfort  Dyspnea, orthopnea, paroxysmal nocturnal dyspnea (PND), wheezing  Palpitations, dizziness, syncope  Cough, hemoptysis  Fatigue, weakness  Pain in extremities with exertion (claudication) II. COMMON CAUSES OF CHEST PAIN CONDITION Cardiac Causes




2-10 mins

Pressure, tightness, squeezing, heaviness, burning

Unstable Angina

10-20 mins

Similar to angina but often more severe

> 30 mins

Similar to angina but often more severe


As described for angina


Retrosternal Radiation to neck, jaw, shoulders or arms (left)

Similar to angina


Precipitated by exertion, exposure to cold, psychologic stress

Similar to angina but occurs with low levels of exertion or at rest Unrelieved by nitroglycerin May be associated with evidence of heart failure or arrhythmia Late-peaking systolic ejection murmur radiating to carotids Relieved by sitting up and leaning forward Pericardial friction rub is present

 Acute MI

Aortic Stenosis


Similar to angina

As described for angina

Retrosternal or toward apex Left shoulder and trapezius radiation

Anterior chest, often radiating to the back, between shoulder blades Often unilateral, on the side of embolism

Hours to days


Sudden onset of unrelenting pain

Tearing or ripping sensation; knife-like

Sudden onset







Unilateral, often localized

Sudden onset; several hours


Unilateral on side of

Vascular Causes  Acute Aortic Syndrome (Dissection)

Pulmonary Embolism Pulmonary Hypertension

  

Associated with hypertension and/or underlying connective tissue disorder (e.g., Marfan syndrome) Dyspnea, tachypnea, tachycardia, hypotension Dyspnea Signs of increased venous pressure

Pulmonary Causes Pneumonia Pleuritis Spontaneous Pneumothorax


 

Dyspnea, cough, fever, rales, occasional pleural friction rub Dyspnea Decreased breath



sounds ipsilaterally

Non-Cardiopulmonary Causes 

Esophageal Reflux

10-60 mins


Substernal, epigastric

Esophageal Spasm Peptic Ulcer

2-40 mins



Pressure, tightness, burning Burning

Gallbladder Disease


Aching or colicky

Epigastric. Substernal Epigastric, RUQ, substernal





Herpes Zoster


Sharp or burning

Dermatomal distribution

Variable; may be retrosternal

Emotional/ Psychiatric

Variable; may be fleeting


     

  

Worsened by postprandial recumbency Relieved by antacids Can closely mimic angina Relieved by food intake or antacids May follow meals Precipitated by fatty meals May be reproduced by localized or pinpoint pressure on exam Vesicular rash Situational factors precipitates symptoms Often with history of anxiety/depression


Peripheral Cyanosis

Differential Cyanosis

Homan’s Sign

Kussmaul’s Sign

   

Abdominojugular Reflux

REMARKS Cyanosis due to right-to-left shunting, allowing deoxygenated blood to reach systemic circulation Cyanosis due to reduced extremity blood flow due to small vessel vasoconstriction Isolated cyanosis affecting the lower extremities but not the upper (seen in large PDA) Posterior calf pain on active dorsiflexion of the foot against resistance (suggestive of DVT) Rise or a lack of JVP with inspiration, associated with constrictive pericarditis Normally, the venous pressure should fall by at least 3 mmHg with inspiration Pressure over the upper abdomen (RUQ) for at least 10 seconds Positive response: sustained rise of >3 cm in JVP for at least 15 seconds after release of the hand



LV Enlargement RV Enlargement Peripheral Pulses PulsusParvus et Tardus Bifid Pulse

 


 

Located in the left 5th ICS, mid-clavicular line Normal apex is a localized systolic outward thrust, less than 2.5 cm in diameter Apical impulse is shifted laterally & downwards Sustained systolic lift / heave in the left parasternal area A weak and delayed pulse that suggest severe aortic stenosis Two systolic peaks can be appreciated, described in hypertrophic obstructive cardiomyopathy (HOCM), with inscription of percussion and tidal waves Refers to a fall in SBP > 10mmHg with inspiration, seen in patients with:



pericardial tamponade, massive pulmonary embolism, hemorrhagic shock, severe obstructive lung disease, tension pneumothorax) Beat-to-beat variability of pulse amplitude seen in severe LV systolic heart failure


Second Heart Sound (S2)

   

   

Third Heart Sound (S3)

Fourth Heart Sound (S4)  

REMARKS Coincides with closure of the mitral valve and tricuspid valve (Systolic Pressure) Caused by the closure of the aortic and pulmonic valves (Diastolic Pressure) Indicates end of systole (or beginning of diastole) Best heard at the base; splitting is normally heard Variations include: - Widened Interval: RBBB, severe MR - Narrowly Split or Singular S2: Pulmonary arterial HPN - Fixed Splitting: ASD secundum - Paradoxical Splitting: LBBB, RV apical pacing, severe AS, HOCM, MI Coincides with early diastole or rapid ventricular filling It is caused by the flow of blood during rapid ventricular filling Best heard after S2 Coincides with late diastole or atrial systole (atrial contraction/slow ventricular filling) Diminished ventricular compliance increases resistance to ventricular filling More common in chronic LCH or active MI

B. Common Auscultatory Areas of the Heart AREA LOCATION Aortic Area  From the 2nd to 3rd ICS at the right sternal border Pulmonic Area  From the 2nd to 3rd ICS at the left sternal border Tricuspid Area  From the 3rd to 5th ICS at the left sternal border Mitral Area  Near the apex of the heart at the 5th ICS in the left mid-clavicular line C. Grading of Murmurs GRADE Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Grade 6 D. Common Murmurs POSSIBLE DIAGNOSIS Pulmonic / Aortic Stenosis Aortic Regurgitation Tricuspid or Mitral Regurgitation

     

VOLUME Faint; needs concentration Faint but can be heard readily by an experience observer Moderately loud Loud Very loud; heard with stethoscope lightly pressed on the skin Exceptionally loud; heard with stethoscope slightly above the chest wall

Tricuspid or Mitral Stenosis Mitral Valve Prolapse

      

DESCRIPTION OF MURMUR Systolic ejection murmur Early diastolic murmur Holosystolic (pansystolic) murmur if chronic Early systolic murmur if acute Murmur of TR usually increases with inspiration (Carvallo sign) Late diastolic murmur / rumble Systolic click with mid-to-late systolic murmur

E. Other Sounds SOUND Opening Snap (OS) Pericardial Knock Tumor Plop

  

DESCRIPTION High-pitched and occurs after a very short interval following S2 From the 2nd to 3rd ICS at the left sternal border From the 3rd to 5th ICS at the left sternal border

THRILL? No No No Yes Yes Yes



 

Holter Monitoring

 

Stress Testing  Electrophysiology Study (EPS) Transthoracic Echocardiography (TTE) Transesophageal Echocardiography (TEE)

  

Cardiac Magnetic Resonance Imaging (MRI) Computed Tomography Angiography (CTA)

   

Nuclear Imaging Intravascular Ultrasound

Coronary Angiography

 

Cardiac Catheterization

II. MAKING A CARDIAC DIAGNOSIS COMPONENT 1. Underlying Etiology   2. Anatomic Abnormalities    3. Physiologic Disturbances   4. Functional Disability 

REMARKS Widely used to visualize the heart and lungs Graphic recording of electric potentials generated by the heart to detect arrhythmias, conduction disturbances and ischemia Continuous ECG rhythm pattern for 24 hours or more to document paroxysmal rhythm abnormalities Non-invasive tool to evaluate the cardiovascular system’s response to stress under controlled conditions: o Exercise stress test: least invasive, makes use of a treadmill o Pharmacologic stress test: drugs are used to induce stress (e.g., dobutamines) Electrophysiological test of the heart involving intracardiac catheters with electrodes probing the endocardium to test conduction pathways and electrical activity Uses ultrasound waves to visualize heart chambers and valves Using Doppler studies, it can visualize blood flow through the heart Echocardiography that uses a specialized probe with an ultrasound transducer introduced into the esophagus to more accurately visualize posterior structures Differentiates soft tissues better than CT and allows comprehensive exams for assessment of size, morphology, function and tissue characteristics Displays vessels in the body (e.g., coronaries, aorta) May also be used to detect calcium in the coronary arteries Uses radioisotopes (Technetium, Thallium) taken up by viable myocardial cells to assess myocardial perfusion, viability & function (ischemic myocardium takes up less isotope) Percutaneous procedure that uses catheters to visualize the lumen and the interior wall of blood vessels Determines the patency and configuration of the coronary artery lumen by injecting contrast material into the coronary arteries Uses invasive monitoring and blood sampling through a catheter inserted into the heart to determine function, pressures, oxygenation, flow and volume of blood within the chambers and great vessels

IMPORTANT QUESTIONS Congenital, hypertensive, ischemic or inflammatory? Which chambers are involved? Are they hypertrophied, dilated or both? Which valves are affected? Are they regurgitant and/or stenotic? Is there pericardial involvement? Has there been a myocardial infarction? Is an arrhythmia present? Is there evidence of congestive heart failure or of myocardial ischemia? How strenuous is the physical activity required to elicit symptoms?

Example: Ischemic Heart Disease, Chronic Stable Angina Pectoris, CCS 3 Congestive Heart Failure NYHA FC III, in Sinus Rhythm




TC = HDL + Non HDL TC = HDL + [LDL + VLDL] TC = HDL + LDL + TG 5

    

TC = total cholesterol in mg/dL HDL = high density lipoprotein in mg/dL LDL = low density lipoprotein in mg/dL VLDL = very low density lipoprotein in mg/dL (estimated by dividing TG level by 5) TG = triglycerides in mg/dL

B. Individual Components 1. High Density Lipoproteins (HDL)  Removes cholesterol from peripheral tissues via the reverse cholesterol transport  Low HDL values < 40 mg/dL increased risk for heart disease 2. Non-High Density Lipoproteins (Non-HDL)  Includes low density lipoproteins (LDL) and very low density lipoproteins (VLDL)  Lower non-HDL cholesterol is desirable and is associated with a lower risk of heart disease  Value can be estimated from other lipid values when non-HDL level is not directly available:


 

If VLDL values are not given, it can be estimated by dividing triglyceride levels by 5 Non-HDL are ApoB-100 containing atherogenic lipoproteins

C. The Lipoproteins  Composed of varying proportions of cholesterol, triglycerides and phospholipids  LDL and HDL carry most cholesterol LIPOPROTEIN REMARKS  Delivers dietary triglyceride to peripheral tissues Chylomicron  Delivers cholesterol to the liver in the form of chylomicron remnants  Delivers hepatic triglycerides to peripheral tissues (TG > cholesterol VLDL esters)  Secreted by the liver  Formed in the degradation of VLDL IDL  Delivers triglycerides and cholesterol to the liver, where they are degraded into LDL  Delivers hepatic cholesterol to peripheral tissues LDL  Formed by lipoprotein lipase modification of VLDL in the peripheral tissues HDL  Mediates reverse cholesterol transport (from periphery back to the liver) II. THE ACC/AHA 2013 GUIDELINES ON THE TREATMENT OF BLOOD CHOLESTEROL  Statin therapy is recommended for individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk who are most likely to experience a net benefit (benefit>harm)  There is insufficient evidence to support continued use of specific LDL-C and/or non-HDL-C treatment “targets”  Appropriate intensity of statin therapy should be used to reduce risk in those most likely to benefit


Non-statin therapies (e.g., fibrates, niacin), whether alone or in addition to statins, provide little benefit in risk reduction

A. Four Major Statin Benefits Groups (ASCVD risk reduction outweighs risk of adverse events) 1. Acute coronary syndrome or history of MI 1 Patients with clinical ASCVD 2. Stable or unstable angina 3. Coronary or other arterial revascularization 4. Stroke, TIA or PAD 2 Primary elevations of LDL-cholesterol > 190mg/dL 3 Patients 40-75 years + LDL 70-189 mg/dL + Diabetes (without clinical ASCVD) 4 Patients 40-75 years + LDL 70-189 mg/dL + Estimated 10-year ASCVD risk > 7.5% (without clinical ASCVD or diabetes) B. Pooled Cohort Equations for ASCVD Risk Reduction  For the fourth group, risk prediction is done by using the pooled cohort equations for ASCVD risk prediction (developed by the Risk Assessment Work Group)  Calculator is not appropriate for those with known ASCVD  Calculator is available online at 

Computes for hard ASCVD events, including: o o o

Non-fatal MI Death due to coronary heart disease (CHD) Fatal or non-fatal stroke

Data includes: o Age, sex and race o Total cholesterol and HDL levels o Systolic BP o Treatment for hypertension o Diabetes o Smoking history

C. Major Recommendations for Statin Therapy for ASCVD Prevention Clinical ASCVD

LDL > 190 mg/dL

Age > 75

High Intensity Statin (Class I)

Moderate Intensity Statin (Class II)

Diabetes + 40-75

10 year ASCVD risk > 7.5% and Age 40-75

Moderate Intensity Statin if risk is 5 to 7.5% (Class IIa) *


D. Intensity of Statin Therapy HIGH-INTENSITY THERAPY Daily dose lowers LDL by > 50%

MODERATE-INTENSITY THERAPY Daily dose lowers LDL by 30 to  With 5 to 7.5% 10-year ASCVD risk For LDL-C >190 mg/dL: (without ASCVD or DM); moderate-to-high intensity  > 21 years + primary LDL-C > 190 mg/dL (risk Individuals in whom high-density statin estimation is not therapy would be recommended but required) have characteristics predisposing them to statin-associated adverse effects** Secondary Prevention  < 75 years + clinical  > 75 years or safety concerns + ASCVD clinical ASCVD

LOW-INTENSITY THERAPY Daily dose lowers LDL by < 30% Simvastatin 10 mg Pravastatin 10-20 mg Lovastatin 20 mg Fluvastatin 20-40 mg Pitavastatin 1 mg

Individualized (e.g., patients who recover from mid-to-moderate muscle symptoms with higher doses of statins)

*For patients 40-75 years old with LDL 70-189 mg/dL and DM, moderate- (class I recommendation) or high-intensity (class Iia recommendation if risk for ASCVD is >7.5%) may be considered, depending on the risk-benefit ratio. **Multiple or serious comorbidities, including impaired renal or hepatic function; history of previous statin intolerance or muscle disorders; unexplained alanine aminotransferase (ALT) elevations > 3 times the upper limit of normal (ULN); patient characteristics or concomitant use of drugs affecting statin metabolism; age > 75 years

E. Monitoring  Fasting lipid profile within 4-12 weeks after initiation or dose adjustment and every 3-12 months thereafter  Indicators of anticipated therapeutic response to the recommended intensity of statin therapy (focus is on the intensity of the statin therapy as an aid to monitoring): o High-intensity statin therapy: LDL-C reduction of > 50% from the untreated baseline. o Moderate-intensity statin therapy: LDL-C reduction of 30% to 200 mg/dL (relative) or 500 mg/dL (absolute) Myositis (increased risk if with concomitant statin use) Increase in AST / ALT Most common: nausea

  

Modest LDL reduction Can increase triglycerides

 

 35-50% fasting triglyceride reduction  

 Enhances activity of lipoprotein lipase, leading to decreased VLDL and triglyceride levels


 

 

Reduces hepatic VLDL secretion into circulation and increases HDL significantly Only agent proven to raise HDL levels

  

Flushing Hyperuricemia Impaired glucose tolerance

Primary use: lower triglyceride levels (by reducing triglyceride synthesis in the liver)

 

Bad / fishy taste Dyspepsia

Reduces LDL levels Can reduce HDL levels

 

Can reduce HDL QT interval

F. Potency Equivalence of Statins DOSE OF AGENTS (mg) PERCENT REDUCTION Rosuvastatin Atorvastatin Simvastatin Pravastatin Total Cholesterol LDL-C 10 20 22% 27% 10 20 40 27% 36% 5 20 40 32% 42% 10 40 80 37% 48% 20 80 42% 54% Stained doses on same rows are equipotent (e.g., Rosuvastatin 10 mg is equivalent to atorvastatin 40 mg and both reduce LDL by 48%)


HYPERTENSION I. DIAGNOSIS OF HYPERTENSION  Two or more elevated readings on at least 2 clinic visits over a period of one to several weeks  Definition – adults with: o SBP > 140 mmHg, or o DBP > 90 mmHg II. CLASSIFICATION OF HYPERTENSION A. Classification as to Etiology  Primary / Essential (most common)  Secondary Hypertension B. Clues for Suspecting Secondary Hypertension  Age of onset 50 years  No family history of HPN  DBP >100-120 mmHg  Sudden increase in BP in a patient with stable Stage I HPN  Poor BP control, despite good compliance  Systemic findings (e.g. weight loss/gain, potassium abnormalities) C. Classification as to Stages CLASSIFICATION Normal Pre-hypertension Stage 1 Hypertension Stage 2 Hypertension Isolated Systolic Hypertension D. Definition of Terms VARIATION White Coat Hypertension Resistant Hypertension Orthostatic Hypotension

SYSTOLIC (mmHg) 160 > 140

DIASTOLIC (mmHg) and 100 and 140/90 mmHg and at least two non-clinic-based measurements 20 mmHg or in DBP >10 mmHg in response to assumption of the upright posture from a supine position within 3 minutes


Age > 60

Age < 60

Any Age (+) Diabetes (-) CKD

Any Age (+/-) Diabetes (-) CKD

BP Goal 140 mmHg SBP > 140 mmHg or DBP > 90 mmHg

GOAL BLOOD PRESSURE SBP < 150 mmHg and DBP < 90 mmHg DBP < 90 mmHg SBP < 140 mmHg SBP < 140 mmHg and DBP < 90 mmHg

No. 2 No. 3

Patients < 60 years old

No. 5

Patients > 18 years old with DM

SBP > 140 mmHg or DBP > 90 mmHg

SBP < 140 mmHg and DBP < 90 mmHg


PATIENT POPULATION Non-black population (including those with DM)

No. 4

No. 7

No. 8

No. 9

INITIAL ANTIHYPERTENSIVE AGENT OPTIONS  Thiazide-type diuretic  Calcium channel blocker (CCB)  Angiotensin-converting enzyme inhibitor (ACEI)  Angiotensin receptor blocker (ARB)  Thiazide-type diuretic  Calcium channel blocker (CCB)  Angiotensin-converting enzyme inhibitor (ACEI)  Angiotensin receptor blocker (ARB)

General black population (including those with DM) Patients > 18 years old with CKD (regardless of race or DM status) The main objective of hypertension treatment is to attain and maintain goal BP:  If goal BP is not reached within a month, increase the dose of the initial drug or add a second drug (thiazide-type diuretic, CCB, ACEI or ARB)  If goal BP cannot be reached with 2 drugs, add and titrate a third drug from the list  Do not use an ACEI and an ARB together in the same patient  If goal BP cannot be reached using only the drugs in recommendation 6 because of a contraindication or the need to use more than 3 drugs to reach goal, other classes can be used

IV. MANAGEMENT OF HYPERTENSION A. Screening for Hypertension:  Us Preventive Services Task Force recommends screening for high blood pressure in adults > 18 years old  Screening: o Every 2 years if BP < 120/80 (normal) o Yearly if BP 120-139 / 80-89 (pre-hypertensive) B. Non-Pharmacologic Management: Lifestyle Management for Hypertension ASPECT GOAL Weight Reduction  Attain and maintain BMI < 25 kg/m 2 Dietary Salt Reduction  < 6 g NaCl/day Adapt DASH-type Dietary Plan  Diet rich in fruits, vegetables, and low-fat dairy products  Reduced content of saturated and total fat Moderation of Alcohol  For those who drink alcohol, consume: Consumption o < 2 drinks/day in men o AV-node effect

  

Blocks L-type calcium channels AV node effect > vascular effect

Inhibits ACE Result: angiotensinI is not converted to angiontensin-II

   

 Tachyarrhythmia Edema Headaches

AV block (2nd and 3rd degree) Non-Dihydropyridine   Trifascicular block  Severe LV dysfunction Drugs Acting on the Renin-Angiotensin-Aldosterone-System (RAAS)   ACE-Inhibitors

   

 Cough Angioedema Hyperkalemia Renal agenesis

  

Amlodipine 2.5-10 mg OD Felodipine 2.5-20 mg/OD Nifedipine 30-120 mg/day Diltiazem 120-360 mg/day Verapamil 120-480 mg/day

Captopril 25-150 mg BID-TID Enalapril 2.5-20 mg/day Lisinopril 5-20 mg/day Perindopril 2.5-10


   

Angiotensin Receptor Blockers

Competitive antagonism angiotensin-II


  

Hyperkalemia Renal agenesis Less cough and angioedema

   

 Direct Renin Inhibitor

Directly rennin, enzyme RAAS

inhibits the first in the

   

Angioedema Hyperkalemia Cough Hyperuricemia

Postural hypotension Reflex tachycardia

mg/day Ramipril 2.5-10 mg OD Candesartan 8-32 mg OD Irbesartan 150-300 mg OD Losartan 25-100 mg OD Olmesartan 5-40 mg OD Telmisartan 20-80 mg OD Valsartan 80-320 mg OD

Aliskiren 75-300 mg OD

Prazosin 1-5 mg/day Terazosin 1-5 mg/day Doxazosin 1-8 mg OD Clonidine 75-150 mcg BID-TID Methyldopa 250500 mg BID-TID

Other Anti-Hypertensives  Alpha Blockers

 Central Sympatholytics

 Direct Vasodilators

Blocks the postsynaptic A1receptors found in capacitance & resistance vessels

Activation receptors CNS

of in


Release of nitric oxide, leading to arterial vasodilation

 

         

Sedation Xerostomia Impotence CNS side effects Rebound HPN on withdrawal Reflex tachycardia Headache Hypotension Lupus-like syndrome (for hydralazine) Hypertrichosis (for minoxidil)

 

 

Hyrdrazaline 25 mg TID Minoxidil 2.5-80 mg/day

V. MANAGEMENT OF UNCONTROLLED HYPERTENSION A. Differentiation Between Types of Uncontrolled Hypertension

Usual BP Actual Target Organ Damage Management


SEVERE HYPERTENSION 180-220 / 110-130 mmHg None (asymptomatic) Long-acting oral medication can simple be restarted (usually occurs in chronic hypertensives who stopped taking medication) Require outpatient follow-up within 24-72 hours


HYPERTENSIVE CRISIS > 220/130 mmHg Present (brain, heart, kidney, retina or vessels)

Short-acting oral medications

Immediate reduction of BP with intravenous medication

Require outpatient follow-up within 24 to 72 hours

Admit for monitoring (ICU)


B. Common Intravenous (IV) Drugs for Hypertensive Emergencies DRUG DOSE  5-15 mg/hr as continuous infusion Nicardipine  Starting dose 5 mg/hr, increase q1530 mins by 2.5 mg until goal BP achieved Nitroglycerin  5-200 ug/min  5 ug/min increase q5 mins  0.3-10 ug/kg/min, increase by 0.5 Nitroprusside ug/kg/min q5 mins until goal BP achieved Esmolol  0.5-10 ug/kg/min as bolus  500-300 ug/kg/min as infusion Labetalol  0.25-0.5 mg/kg; 2-4 mg/min until goal BP is reached, thereafter 5-20 mg/hr


Liver failure

Can cause headaches

 

Liver/kidney failure Can cause cyanide toxicity

2nd or 3rd degree AV block, systolic heart failure, bradycardia, COPD 2nd or 3rd degree AV block, systolic heart failure, bradycardia, COPD

C. Recommended Treatment of Hypertensive Emergencies Based on End-Organ Involvement TYPE OF EMERGENCY TIMELINE, TARGET BP THERAPY* HPN Crisis with  Several hours  Labetalol, Nitroprusside, Retinopathy or Acute Nicardipine  Target MAP: decrease by 20% t0 25% Renal Insufficiency HPN Encephalopathy  Immediate  Labetalol, Nicardipine, Nitroprusside  Target MAP: decrease by 20% to 25% Acute Aortic Dissection  Immediate  Nitroprusside + Metoprolol, Labetalol  Target SBP < 110 mmHg Acute Pulmonary Edema  Immediate  Nitroprusside + Loop Diuretic, Nitroglycerin  Target MAP: 60-100 mmHg Acute Coronary Syndrome  1 hour  Nitroglycerin, Labetalol  Target MAP: 60-100 mmHg Acute Ischemic Stroke and  1 hour  Labetalol, Nicardipine, BP > 220/120 mmHg Nitroprusside  Target MAP: decrease by 5% Cerebral Hemorrhage and  1 hour  Labetalol, Nicardipine, SBP > 180 mmHg or MAP > Nitroprusside  Target SBP: < 180 mmHg and MAP 130 130 mmHg mmHg  Several hours  Phentolamine (after Cocaine intoxication benzodiazepines),  Target SBP: < 140 mmHg Nitroprusside  Labetalol + MgSO4 and oral Severe preeclampsia/  Immediate anti-HPN, Nicardipine eclampsia  Target BP: < 160/105 mmHg  Emergency Delivery of Fetus *Those underlined: first-line therapy

VI. HYPERTENSION AND PREGNANCY  Four categories of hypertension in pregnancy: 1. Pre-eclampsia: severe progressive multisystem disorder diagnosed by hypertension accompanied by any one of the following: o Proteinuria o BP of 160/110 mmHg or higher despite bed rest o Thrombocytopenia o Impaired liver function o Progressive renal insufficiency o Pulmonary edema o New-onset cerebral or visual disturbance 2. Chronic hypertension: hypertension predating pregnancy 3. Chronic hypertension with superimposed preeclampsia 4. Gestational hypertension: BP elevation after 20 weeks gestation in the absence of the additional systemic features listed above


HEART FAILURE (HF) I. ETIOPATHOGENESIS  A clinical syndrome consisting of a constellation of clinical symptoms (dyspnea & fatigue) and signs (edema and rales) that lead to frequent hospitalization, a poor quality of life, and a shortened life expectancy.  Etiologies: o Coronary artery disease (CAD): most common cause of HF in industrialized countries (60-75%) o Hypertension: cause of HF in 75% of patients o Idiopathic cardiomyopathy: 20-30% of depressed EF HF o Pulmonary heart disease: cor pulmonale, pulmonary vascular disorders o High output states: thyrotoxicosis, nutritional disorders (beriberi), excessive blood flow requirements, chronic asthma II. CLASSIFICATION / STAGES OF HEART FAILURE (HF) A. Classification Based on Function / Ejection Fraction (EF) TYPE EJECTION DESCRIPTION FRACTION Progressive disorder initiated by an Systolic Heart Depressed HF index event (e.g., MI, volume Failure or HF with < 40% overload, chronic anemia) that leads reduced EF (HfrEF) to a decline in the pumping capacity of the heart Proposed mechanisms include Diastolic Heart diastolic dysfunction and extraFailure or HF with Preserved EF cardiac mechanisms such as preserved EF > 40-50% increased vascular stiffness and (HfpEF) impaired renal function (still undefined and evolving) Occur when the body’s requirements Normal at first, then for oxygen and nutrients are High-Output Heart may decrease over increased and the demand outstrips Failure time what the heart can provide


CAD (e.g., MI) Dilated cardiomyopathy Valvular heart disease

Pathologic hypertrophy (HOCM, HPN) Aging, fibrosis Restrictive cardiomyopathy

     

Thyrotoxicosis Beriberi Chronic anemia Systemic arteriovenous shunting

B. American College of Cardiology / American Heart Association (ACC/AHA) Stages of Heart Failure STAGE DESCRIPTION EXAMPLES At high risk for HF but without structural heart Patients with HPN, CAD, DM or patients using A disease or HF symptoms cardiotoxins or with family history of cardiomyopathy Structural heart disease but without signs or Patients with previous MI, LV systolic dysfunction, or B symptoms of HF asymptomatic valvular disease Structural heart disease with previous or Patients with known structural heart disease with C current symptoms of HF shortness of breath, fatigue, reduced exercise tolerance Refractory HF requiring specialized Patient who have marked symptoms at rest despite interventions maximal therapy (e.g., patients with recurrent D hospitalizations or cannot be safely discharged without special interventions) C. New York Heart Association (NYHA) Functional Classification NYHA DESCRIPTION Symptoms occur with greater than ordinary  I physical activity  Symptoms occur with ordinary physical activity  II  Symptoms occur with less than ordinary  III physical activity  Symptoms may be present even at rest  IV 

COMMENTS No limitation of physical activity Can climb > 2 flights of stairs with ease Slight limitation of physical activity Can climb 2 flights of stairs but with difficulty Marked limitation of physical activity Can climb 8 cm H2O Sinus tachycardia due to increased adrenergic activity Point of maximal impulse displaced due to cardiomegaly S3 (protodiastolic gallop) at the apex: usually in volume overloaded patients S4: usually in diastolic dysfunction Crackles: transudation of fluid from intravascular space to alveoli Expiratory wheezes: cardiac wheezing caused by peribronchial cuffing from congestion Pleural effusions: often bilateral; if unilateral, more often on the right Hepatomegaly with pulsation (if with significant TR) Ascites: increased pressure in the hepatic veins Jaundice: impairment of hepatic function due to congestion Peripheral edema: ankles and pre-tibial region Indurated and pigmented skin: long standing edema Peripheral vasoconstriction: cool extremities

IV. DIAGNOSIS OF HEART FAILURE  The diagnosis of HF is straightforward when the patients presents with classic signs and symptoms  Key to diagnosis is a high index of suspicion A. Framingham Criteria for Heart Failure MAJOR CRITERIA MINOR CRITERIA  Paroxysmal nocturnal dyspnea (PND) or orthopnea  Ankle edema  Neck vein distention  Night cough  Rales  Dyspnea on exertion  Cardiomegaly  Hepatomegaly  Acute pulmonary edema  Pleural effusion  S3 gallop  Vital capacity decreased by 1/3 from maximal capacity  Increased venous pressure > 16 cm H2O  Tachycardia > 120 bpm  Hepatojugular reflux  Major or Minor Criteria: Weight loss > 4.5 kg in 5 days in response to treatment The diagnosis of HF requires simultaneous presence of at least:  1 Major Criteria, or  1 Major Criterion + 2 Minor Criterion


(use of minor criteria acceptable only if they cannot be attributed to another medical condition, such as pulmonary HPN, chronic lung disease, cirrhosis, ascites, nephrotic syndrome)

B. Diagnostics in HF DIAGNOSTICS 2D Echocardiography with Doppler 12-L ECG Chest Radiography Cardiac Biomarkers (BNP) Complete Blood Count Serum Electrolytes, BUN, Crea, AST, ALT FBS, OGTT Lipid Profile FT4, TSH

            

DESCRIPTION Most useful test, evaluation of ejection fraction (EF) Semi-quantitative assessment of LV size, function, wall motion abnormalities, valvular defects Assess cardiac rhythm, LV hypertrophy, prior MI A normal ECG virtually excludes LV systolic dysfunction Assess the cardiac size and shape and state of pulmonary vasculature Identify non-cardiac causes of symptoms Relatively sensitive markers for the presence of HF Increase with age and renal impairment Look for anemia, signs of infection, and bleeding (may precipitate / worsen HF) Assess for electrolyte disturbances, beginning cardiorenal syndrome, ischemic hepatitis or chronic passive congestion of the liver Assess for diabetes Assess for dyslipidemia Assess for thyroid hormone abnormalities

V. MANAGEMENT OF HEART FAILURE A. Non-Pharmacologic Management and Basic Principles  Sodium restriction: limit Na+ intake to 2-3 g/day in all patients with HF; and to less than 2 g/day in patients with moderate to severe HF  Fluid restriction: generally unnecessary unless with hyponatremia (< 130 mEq/L) and volume overload  Caloric supplement: for those with cardiac cachexia B. Pharmacologic Management for Prevention and Treatment of Chronic Heart Failure DRUG CLASS DESCRIPTION / MECHANISM DOSE  Cornerstone of modern HF treatment  Captopril 25-50 mg TID  Interferes with RAAS by inhibiting the conversion of angiotensin I to  Enalapril 2.5-10 mg BID ACE-Inhibitors angiotensin II  Ramipril 2.5-10 mg OD  Inhibits kininase which may lead to  Lisinopril 5-20 mg OD increase in bradykinin (ACE-I induced cough) Angiotensin Receptor  Use if ACEI intolerant (e.g., cough,  Valsartan 40-160 mg BID Blockers angioedema)  Candesartan 8-32 mg OD  Losartan 25-50 mg OD  Another cornerstone of modern HF treatment  Carvedilol 3.125-25 mg BID Beta Blockers  Interferes with sustained activation of  Bisoprolol 1.25-10 mg OD the adrenergic nervous system,  Metoprolol succinate 25-200 mg OD particularly the deleterious effects of B1 activation  Inhibits action of aldosterone in Aldosterone Antagonist collecting duct  Spironolactone 25-50 mg OD  May also be used for fluid retention  Eplerenone 25-50 mg OD (diuretic)  For symptomatic LV dysfunction + Digoxin atrial fibrillation  Digoxin 0.125-0.375 mg OD  Add-on to standard therapy  Reduces HR by inhibition of the  Ivabradine 5-7.5 mg BID Ivabradine “funny channel” (If) in the SA node  Primarily used for symptomatic


stable angina May be used for HF with systolic dysfunction in patients with sinus rhythm and HR > 70 bpm

C. Management of Fluid Retention in Chronic HF DRUG CLASS DESCRIPTION / MECHANISM  Act on the loop of Henle by reversibly Loop Diuretics inhibiting the reabsorption of Na+, K+, Cl in the thick ascending limb  Reduce the reabsorption of Na+ and Cl in Thiazide and Thiazidethe first half of the distal convoluted tubule Like-Diuretics  Tend to lose their efficiency with moderate to severe renal insufficiency (Crea > 2.5 mg/dL)  Interfere with action at the vasopressin Arginine Vasopressin receptors Antagonists  Primarily used for treatment of hyponatremia by stimulating free-water excretion and improving plasma Na+concentration D. Indications for Use of Drugs in HF CLASS ASYMPTOMATIC LV DYSFUNCTION (NYHA I) ACEI/ARB Yes Diuretic No B-Blocker Yes, if Post-MI Aldosterone Yes, if Recent MI Antagonist Digoxin May be considered*

 

DOSE Furosemide 20-40 mg OD-BID Bumetanide 0.5-1.0 mg ODBID Hydrochlorothiazide 25 ODBID Indapamide 2.5 mg OD Metolazone 2.5-5.0 mg OD

 

Tolvaptan 15 mg OD Satavaptan 25 mg OD

  

SYMPTOMATIC HF (NYHA II) yes Yes, if with fluid retention Yes Yes



May be considered*



*Digoxin may be considered for patients with NYHA-I for rate control in AF or when improved from more severe HF and in sinus rhythm

E. Devices Used in HF  Cardiac resynchronization therapy (CRT) or biventricular pacing: device used to restore synchrony of the left ventricle in patients with HF and a widened QRS complex  Implantable cardioverter-defibrillator (ICD): device to treat tachyarrhythmias for primary / secondary prophylaxis against sudden cardiac death VI. ACUTE DECOMPENSATED HEART FAILURE (ADHF) A. Distinctive Phenotypes ACUTE DECOMPENSATION Typical Pulmonary Edema

Low Output


Normo-hypertensive Usually not volume overloaded Severe pulmonary congestion with hypoxia

   

Hypoperfusion with end-organ dysfunction Low pulse pressure, cool extremities Cardiorenal syndrome, hepatic congestion Hypotension, low cardiac output, end-organ failure Extreme distress, pulmonary congestion, renal failure

Cardiogenic Shock 


Vasodilators, diuretics

      

Vasodilators, diuretics, opiates O2 non-invasive ventilation Inotropic therapy Vasodilators Hemodynamic monitoring Inotropic therapy Mechanical circulatory support


B. Parenteral Therapy for Acute Decompensated HF DRUG CLASS SAMPLE DRUGS Inotropic Therapy  Dobutamine (2-20 mcg/kg/min)  Others: Milrinone, Levosimendan Vasodilators  Nitroglycerine (10-20 mcg/kg/min)  Others: Nesiritide, Nitroprusside, Serelaxin  Furosemide (20-240 mg/day) Diuretics  Bumetamide (0.5-5 mg/day)  Others: Torsemide, Metolazone, Chlorthalidone, Spironolactone, Acetazolamide

CHRONIC STABLE ANGINA PECTORIS (CSAP) Patients with ischemic heart disease (IHD) fall into two large groups:  Chronic artery disease (CAD) who commonly present with chronic stable angina pectoris (CSAP)  Acute coronary syndromes (ACS), discussed in the next section, are composed of: o Non ST-segment elevation acute coronary syndrome (NSTE-ACS) o ST-segment elevation acute myocardial infarction (STEMI) I. ETIOPATHOGENESIS  Inadequate supply of blood flow and oxygen to a portion of the myocardium causing inadequate perfusion of myocardium supplied by an involved artery  Most common cause: atherosclerotic disease of an epicardial coronary artery  Obesity, insulin resistance, and T2DM are increasing and powerful risk factors for IHD II. CLINICAL MANIFESTATIONS A. Angina  Typical history involves a man >50 years old or woman >60 years old who complains of chest discomfort: o Described as heaviness, pressure, squeezing, smothering or choking o Crescendo-decrescendo in nature o Usually lasts 2-5 minutes o Associated with physical exertion or stress o Radiation to either or both shoulders/arms, but does not radiate to the trapezius muscles o Relieved within 5-10 minutes by rest and/or sublingual NTG o Levine’s sign: hand placed over sternum with a clenched fist to indicate discomfort B. Canadian Cardiovascular Society Classification of Angina CCS CLASS DESCRIPTION I Angina occurs with greater than ordinary physical activity II Angina occurs with ordinary physical activity III Angina occurs with less than ordinary physical activity IV Angina may be present even at rest III. DIAGNOSIS A. Non-Invasive Diagnostics DIAGNOSTIC TEST ECG Stress Testing

    

2D Echo 

EXPECTED FINDINGS May be normal at rest ST-segment and T-wave changes, LV hypertrophy, intraventricular conduction disturbance (which may be non-specific) Most widely used for both diagnosis of IHD and estimating prognosis Involves recording the 12-lead ECG before, during and after exercise Used to assess left ventricular function in patients with CSAP and patients with a history of a prior MI, pathologic Q waves or clinical evidence of CHF Assess for wall motion abnormalities, ejection fraction, presence of thrombus, etc.


B. Indications for Coronary Angiography  Patients with CSAP who are severely symptomatic despite medical therapy and considered for revascularization  Patients with troublesome symptoms that present diagnostic difficulties in whom there is a need to confirm or R/O the diagnosis of IHD  Patients with known or possible CSAP who have survived cardiac arrest  Patients with CSAP or evidence of ischemia on noninvasive testing with clinical or laboratory evidence of ventricular dysfunction  Patients at high risk of sustaining coronary events on noninvasive testing, regardless of symptoms IV. MANAGEMENT OF CSAP A. Pharmacologic Treatment for Angina DRUG CLASS EXAMPLES Anti-Ischemic Drugs



   Nitrates 

  B-Blockers (BB)   

Isosorbide Dinitrate (ISDN) 10-40 mg BIDTID Isosorbide Mononitrate (ISMN) 30-240 mg OD NTG 0.3-0.6 mg SL, as needed up to 3 doses, 5 mins apart NTG Transdermal Patch 0.2-0.8 mg/hr OD (remove at bedtime for 12-14 hrs)

Metoprolol 50-100 mg BID-QID Metoprolol XL 50-200 mg OD Carvedilol 3.125-50 mg BID Atenolol 50-100 mg OD Bisoprolol 5-20 mg OD

 

Systemic venodilation with reduction in LV end-diastolic volume and pressure, thereby reducing myocardial wall tension and O2 requirements Dilation of epicardial coronary vessels Increased blood flow in collateral vessels

 

 

Reduced myocardial O2 demand by inhibiting increases in HR, arterial pressure and myocardial contractility caused by adrenergic activation

 

Calcium Channel Blockers (CCB)

Non-dihydropyridines  Verapamil 80-120 mg TID-QID  Diltiazem 30-90 mg TID-QID Dihydropyridines  Amlodipine 2.5-10 mg OD  Felodpine 2.5-10 mg OD

Coronary vasodilators that produce variable and dose dependent reductions in myocardial O2 demand, contractility, and arterial pressure

None of the longacting nitrates are as effective as SL NTG for the acute relief of angina Used for symptomatic relief May be discontinued with the disappearance of chest pain Common side effect limiting their use: headache At least 8 hour nitrate-free interval is recommended to avoid nitrate tolerance Cornerstone therapy for angina Shown to improve life expectancy following acute MI

Indicated in patients with: o Inadequate responsiveness to the combination of BB and nitrates o Adverse reactions to BB o Angina history of asthma or COPD o Sick sinus syndrome or significant AV conduction disturbances o Prinzmetal’s angina o Symptomatic


peripheral arterial disease Other Pharmacologic Agents for Angina  Inhibitor of the IF ion channel (principal determinant of Ivabradine the SA node) 2.5-7.5 mg BID  Slows the heart rate through a mechanism that is not associated with negative inotropic effects  Dilates peripheral and coronary resistance vessels via Nicorandil ATP-sensitive K+ channels 10-20 mg BID  Possess a nitrate moiety that promotes venous and coronary dilation B. Other Drugs for Stable Angina Pectoris DRUG CLASS EXAMPLES 

Aspirin 75-162 mg OD

Clopidogrel 75 mg OD


 Statins

 

 Rosuvastatin 10-20 mg OD Atorvastatin 10-80 mg OD Simvastatin 10-40 mg OD

C. Coronary Interventions INTERVENTION Percutaneous Coronary Intervention (PCI)

Coronary Artery Grafting (CABG)

MECHANISM OF ACTION  Irreversible inhibitor of platelet cyclooxygenase activity, interfering with platelet activation  Oral agent that blocks ADP receptor-mediated platelet aggregation


 Act as HMG-CoA reductase inhibitor Exhibit pleiotropic effects: plaque stabilization and antiinflammatory effects

Only works in patients who are in sinus rhythm

Has anti-anginal efficacy similar to BB, nitrates & CCBs

COMMENTS Chronic administration has been shown to reduce coronary events May be substituted for aspirin in those with aspirin hypersensitivity or those who cannot tolerate aspirin Can lower LDL cholesterol (25-50%), raise HDL cholesterol and lower triglycerides High intensity statin therapy should be given for patients with established IHD who are less than 75 years old, in the absence of contraindications

DESCRIPTION  Balloon dilatation usually accompanied by coronary stenting  Most common indication: persistent or symptom-limiting angina pectoris, despite medical therapy, accompanied by evidence of ischemia during a stress test  Indicated for those with three-vessel CAD or two-vessel CAD with involvement of the left anterior descending artery (LAD) or stenosis of the left main coronary artery


Operational term that refers to a spectrum of conditions compatible with acute myocardial ischemia and/or infarction due to an abrupt reduction in coronary blood flow Patients with ACS are composed of: o Non-ST segment elevation acute coronary syndrome (NSTE-ACS):  Non-ST segment elevation myocardial infarction (NSTEMI)  Unstable angina (UA)  ST elevation acute myocardial infarction (STEMI)


I. UNIVERSAL DEFINITON OF MYOCARDIAL INFARCTION A. Criteria for Acute MI “Acute MI” should be used when there is evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. Under these conditions, any of the following criteria meet the diagnosis for MI:  Detection of a rise and/or fall in cardiac biomarkers (preferably cardiac troponins/cTn), with at least one value above the 99th percentile with at least one of the following: o Symptoms of ischemia o New or presumed new significant ST-segment and/or T wave changes or new LBBB o Development of pathologic Q waves on the ECG o Imaging evidence of new loss of viable myocardium or new wall motion abnormality o Identification of an intracoronary thrombus by angiography or autopsy  Cardiac death with symptoms suggestive of myocardial ischemia & presumed new ischemic ECG changes or new LBBB (Type 3)  PCI-related MI (Type 4a)  Stent thrombosis associated with MI (Type 4b)  CABG-related MI (Type 5) B. Criteria for Previous Myocardial Infarction (any of the following):  Pathologic Q waves with or without symptoms in the absence of non-ischemic causes  Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract in the absence of a non-ischemic cause  Pathologic findings of previous MI II. UNIVERSAL CLASSIFICATION OF TYPES OF MYOCARDIAL INFARCTION TYPE OF MYOCARDIAL INFARCTION DESCRIPTION (MI) Related to atherosclerotic plaque rupture, ulceration, fissuring, erosion or Type Spontaneous MI dissection with resulting intraluminal thrombus in one or more of the 1 coronary arteries that leads to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis A condition other than CAD contributes to an imbalance between MI secondary to myocardial oxygen supply and/or demand, e.g., coronary endothelial Type Ischemic Imbalance dysfunction, coronary artery spasm, coronary embolism, 2 tachyarrhythmias/bradyarrhythmias, anemia, respiratory failure, hypotension, and hypertension with or without LVH MI resulting in Death Cardiac death with symptoms suggestive of ischemia and presumed new Type when Biomarkers are ischemic changes (or new LBBB), but death occurring before blood 3 Unavailable samples could be obtained MI associated with PCI defined by elevation of cTn values to >5x the 99th percentile of the upper reference limit in those with normal baseline values or a rise in cTn values >20% if baseline values are elevated and are stable or falling; AND either: MI related to PCI  Symptoms suggestive of myocardial ischemia Type  New ischemic changes on the ECG or new LBBB 4a  Angiographic loss of patency of a major coronary artery or a side branch or persistent slow flow or no flow or embolization  Imaging demonstration of new loss of viable myocardium or new regional wall motion abnormality MI associated with stent thrombosis is detected by coronary angiography Type MI related to Stent or autopsy in the setting myocardial ischemia and with a rise and/or fall in 4b Thrombosis cardiac biomarkers with at least one value >99th percentile of the upper reference limit MI associated with CABG – defined by elevation of cardiac biomarker values >10x the 99th percentile of upper reference limit in patients with Type MI related to CABG normal baseline values; AND either: 5  New pathologic Q waves or new LBBB, or  New graft or new native coronary artery occlusion on angiogram,


or Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality

NON-ST ELEVATION ACUTE CORONARY SYNDROME (NSTE-ACS) I. ETIOPATHOGENESIS  Most commonly caused by an imbalance O2 supply and demand, resulting from a partially occluding thrombus forming on a disrupted atherothrombotic coronary plaque on eroded coronary artery endothelium A. Four Basic Pathophysiologic Processes:  Most common cause: plaque rupture or erosion with superimposed non-occlusive thrombus  Dynamic obstruction (e.g., coronary spasm as in Prinzmetal’s variant angina)  Severe mechanical obstruction  Increased myocardial O2 demand (e.g., tachycardia) and/or decreased supply (e.g. anemia) B. Definition of Terms TERM

Unstable Angina (UA)


Prinzmetal Variant Angina

DEFINITION Angina or equivalent ischemic discomfort with at least one of the following:  Occurs at rest (or with minimal exertion), usually lasting >10 minutes  Severe and of new onset (e.g., within the prior 4-6 weeks) of at least CCS III severity  Occurs with crescendo pattern (e.g., distinctly more severe, prolonged or frequent than previous episodes)  Clinical features of UA plus evidence of myocardial necrosis (elevated cardiac biomarkers)  Ischemic pain that occurs at rest but not usually with exertion, associated with transient ST-segment elevation  Due to transient, focal spasm of an epicardial coronary artery

II. CLINICAL MANIFESTATIONS A. Typical Chest Pain  Chest discomfort is typically severe and has at least one of the following features: o Occurs at rest (or with minimal exertion), lasting >10 minutes o Relatively recent onset (within prior 2 weeks) o Occurs with a crescendo pattern (e.g., more severe, prolonged or frequent) B. Symptoms & Signs of NSTE-ACS SYMPTOMS  Chest pain radiating to the neck, left shoulder, and left arm  Dyspnea  Diaphoresis  Anxiety, restlessness

SIGNS     

Pale cool skin Sinus tachycardia S3 or S4 Basilar rales Hypotension

III. DIAGNOSIS OF NSTE-ACS A. 12-Lead Echocardiogram (ECG)  ST-segment depression, transient ST-segment elevation or T-wave inversion  T-wave changes: sensitive for ischemia but less specific (unless new & deep T-wave inversions > 0.3 mV)  If initial ECG is not diagnostic – serial ECGs should be done to detect ischemic changes if patient remains symptomatic with a high suspicion for ACS B. Cardiac Biomarkers  Elevated levels distinguish patterns with NSTE-ACS from UA


 

Serial cardiac troponin I or T levels should be obtained at presentation and 3-6 hours after symptom onset to identify a rising and/or falling pattern of values Additional levels should be obtained beyond 6 hours in patients with normal levels on serial examination when ECG and/or clinical presentation confer an intermediate or high index of suspicion for ACS

1. Advantages and Disadvantages of the Common Cardiac Biomarkers CARDIAC TROPONINS  Powerful tool for risk stratification  Greater sensitivity and specificity than Advantage CK  Detection of recent MI up to 2 weeks after onset (remain elevated 7-10 days after MI)  Low sensitivity in very early phase of MI ( 65 years > 3 CAD factors Known CAD (> 50% stenosis) Aspirin use in the [ast 7 days Severe angina in last 24 hours Elevated cardiac markers ST deviation > 0.5mm

POINTS 1 point 1 point 1 point 1 point 1 point 1 point 1 point

INTERPRETATION Risk Total Score: 0-7 points High Risk Score: > 3 points (13% mortality)

IV. MANAGEMENT OF NSTE-ACS A. Standard and Anti-Ischemic Therapy THERAPY Non-Pharmacologic

   

Nitrates 

DESCRIPTION Bed rest with continuous ECG monitoring Supplemental oxygen if O2 sat 100 bpm 2 points > 5 points Killip II-IV 2 points (12% mortality) Weight < 67 kg 1 point Presentation Anterior ST elevation or LBBB on ECG 1 point Time to Treatment > 4 hours 1 point IV. MANAGEMENT OF STEMI A. Pre-hospital Management of STEMI  Major components: o Recognition of symptoms o Rapid deployment of an emergency medical team capable of performing resuscitative maneuvers o Expeditious transportation o Expeditious implementation of reperfusion therapy  Most out-of-hospital deaths from STEMI are due to sudden ventricular fibrillation  Majority of deaths occur within 24 hours of the onset of symptoms (over half occur in the 1st hour) B. Reperfusion Therapy: Primary Goal of Management  Reperfusion Therapy (fibrinolysis or PCI) should be administered to all eligible patients with STEMI with symptom onset within the last 12 hours o Primary PCI: recommended method of reperfusion when it can be performed in a timely fashion o Fibrinolysis: administered at non-PCI-capable centers FIBRINOLYSIS / THROMBOLYSIS INVASIVE STRATEGY (PCI) Generally preferred if: Generally preferred if:  Early presentation (< 3 hours of symptom onset)  Available PCI laboratory with surgical backup o Medical contact-to-balloon or door-to-balloon  Invasive strategy is not available: < 90 minutes  Delay to invasive strategy: o Door-to-balloon minus door-to-needle < 1 hr o Prolonged transport  High risk STEMI (cardiogenic shock, Killip > 3) o Door-to-balloon minus door-to-needle time >1 hr  Contraindications to fibrinolysis o Medical contact-to-balloon or door-to Late presentation (symptom onset > 3 hours) balloon time >90 minutes  Diagnosis of STEMI is in doubt  Fibrinolytic agents:  Percutaneous coronary intervention (PCI) or o Streptokinase percutaneous transluminal coronary angioplasty o Tissue plasminogen activators (PTCA): balloon angioplasty and stenting  Adjunct anti-platelet therapy with fibrinolysis:  Aspirin continued indefinitely

 Anti-platelet therapy during Primary PCI:


Clopidogrel for at least 14 days up to 1 year

o o

Aspirin indefinitely after PCI One P2Y12-receptor inhibitor continued for 1 year for those who receive a stent:  Clopidogrel  Prasugrel (not used if + prior stroke/TIA)  Ticagrelor

 Adjunctive anticoagulant therapy with fibrinolysis: given for a minimum of 48 hours or until revascularization is performed (same dose as in NSTE-ACS)  Anticoagulant therapy during primary PCI: o Unfractioned heparin (UFH) o UFH o Enoxaparin o Bivalirudin o Fondaparinux Fibrinolysis is still reasonable if symptom onset is within 12-24 hours as long as there is evidence of ongoing ischemia (although primary PCI is preferred for this population)

         

CONTRAINDICATIONS TO FIBRINOLYSIS ABSOLUTE CONTRAINDICATIONS RELATIVE CONTRAINDICATIONS Previous intracranial hemorrhage  History of chronic, severe, poorly controlled HPN Structural cerebral vascular lesion (e.g.,  Significant HPN at initial evaluation (SBP > 180 AVM) mmHg or DBP > 110 mmHg) Malignant intracranial neoplasm  History of previous ischemia stroke > 3 months Ischemic stroke within 3 months except  Dementia acute ischemic stroke within 4.5 hours  Intracranial pathology not covered in absolute Suspected aortic dissection contraindications Active bleeding / bleeding diathesis (except  Traumatic or prolonged (>10 minutes) CPR mense)  Major surgery ( 0.24, 2nd or 3rd degree AVB, active asthma, reactive airway disease) ACE-inhibitors should be initiated in the first 24 hours to all patients with anterior wall STEMI, HF or EF < 40% ARB may be used for those intolerant to ACEinhibitors High intensity statin therapy should be initiated or continued

D. Supportive Care THERAPY   Activity  

DESCRIPTION First 12 hours: bed rest Next 12 hours: dangling of feet at bedside and sitting in a chair 2nd and 3rd day: ambulation in the room with increasing duration and frequency to a goal of 185 cm (600 ft) at least 3x a day 2 weeks: resumption of work and sexual activity


 Diet  


Nothing or only clear liquids (due to risk of emesis and aspiration) for the first 4-12 hours Use of stool softener Many require sedation during hospitalization to withstand period of enforced inactivity

E. Secondary Prevention and Long Term Management THERAPY DESCRIPTION Smoking  Complete cessation BP Control  BP 50 years old  Most patients are asymptomatic  Frequent finding in heritable connective tissue disease  Apical mid- or late non-ejection systolic click (characteristic finding) Physical Exam  High pitched late crescendo-decrescendo murmur after systolic click  Murmur is accentuated by standing and strain phase of Valsalva, diminished by squatting and isometric exercises  CXR / ECG: usually normal; but may have biphasic or inverted T in II, III, aVF Diagnostics (inferior leads) on ECG  2D ECHO: systolic displacement of MV leaflets (prolapse) at least 2 mm into LA superior to mitral plane  IE prophylaxis for patients with prior endocarditis Therapy  Symptoms: beat-blockers for palpitations; warfarin if with AF  Intervention: mitral valve repair or replacement (surgery) if with severe MR F. Tricuspid Stenosis (TS)  Generally rheumatic in origin; does not occur in isolation and usually associated with MS  Almost always accompanied by severe TR  Symptoms of right-sided CHF (ascites, edema, hepatosplenomegaly) Physical Exam  Opening snap of TV ~0.06 sec after PV closure  Diastolic murmur at LLSB, augmented during inspiration and reduced during expiration & strain phase of Valsalva Diagnostics  ECG: RAE, RVH  2D ECHO: restriction in opening of the TV Therapy  Salt restriction, bed rest and diuretics  Interventions: surgery


G. Tricuspid Regurgitation (TR)  Physical Exam   Diagnostics    Therapy 

Distended neck veins, hepatomegaly, ascites, (+) hepatojugular reflux Prominent RV pulsation along left parasternal region Carvallo sign: blowing holosystolic murmur at LPSB intensified by inspiration ECG: RAE, RVH 2D ECHO: mosaic color flow across tricuspid valve during systole Isolated TR is usually tolerated and does not require surgery Intervention: valve annuloplasty or replacement for severe cases

H. Pulmonic Regurgitation (PR)  Most common acquired abnormality is regurgitation from severe pulmonary arterial HPN  Graham Steell murmur: high-pitched, decrescendo, diastolic blowing murmur along left sternal border  Intervention: percutaneous pulmonic valve replacement for severe PR

PERICARDITIS I. ETIOPATHOGENESIS  Most common pathology affecting the pericardium and classified clinically and etiologically  May be infectious, non-infectious (MI, uremia, neoplasia, myxedema, cholesterol, chylopericardium, trauma, aortic dissection, post-irradiation, acute idiopathic, sarcoidosis) or presumably related to hypersensitivity or autoimmunity (rheumatic fever, collagen valvular disease, drug-induced, post-cardiac injury) II. CLINICAL MANIFESTATIONS A. Acute Pericarditis (< 6 weeks)  Pain resembles that of acute MI  Chest pain: severe, pleuritic, may be retrosternal or left pericordial and may be referred to neck and, arms or left shoulder  Pericardial pain may be relieved by sitting up and leaning forward and is intensified by lying supine  PE may reveal pericardial friction rub (85%): high-pitched and is described as rasping, scratching or grating and heard most frequently at end-expiration with patient upright and leaning forward B. Chronic (Constrictive) Pericarditis (> 6 months)  Results when the healing of an acute fibrinous or serofibrinous pericarditis or the resorption of a chronic pericardial effusion is followed by obliteration of the pericardial cavity with formation of granulation tissue  Weakness, weight gain, fatigue, increased abdominal girth / ascites and edema  Common in the Philippines: tuberculosis, malignancy and radiation-induced  Kussmaul’s sign: increase in systemic venous pressure with inspiration (in normal conditions, there should be a decrease in pressure with inspiration)  Pericardial knock: early diastolic sound in the left sternal border




Modest increase

Subepicardial inflammation displays:  Stage 1: Diffuse SST-elevation with upward concavity and PR segment depression  Stage 2: ST segments normalize  Stage 3: T-wave inversions  Stage 4: ECG returns to

CHRONIC (CONSTRICTIVE PERICARDITIS)  May be normal-minimally increased  Low voltage QRS complexes  Diffuse flattening or inversion of T-waves  Atrial fibrillation in 1/3 of patients


normal (weeks or months) This is in contrast with ECG findings in AMI wherein ST-elevations are convex, QRS changes occur and Twave inversion is seen within hours before the ST-segments become isoelectric   Echocardiography

  

Pericardial fluid or thickening Differentiate pericarditis from MI: assessment of wall motion

 



    

Pericardial fluid collection Pericardial thickening Bed rest NSAIDs, colchicine Pericardiocentesis if with tamponade

   

Pericardial thickening Septal bounce Dilation of the IVC and hepatic veins Normal ventricular systolic function Flattening of the LV posterior wall Pericardial thickening (more accurate) Pericardial resection / pericardectomy Sodium restriction & diuretics Anti-Koch’s for TB patients Steroids (uncertain benefi)

CARDIAC TAMPONADE I. ETIOPATHOGENESIS  Accumulation of fluid in the pericardial space causes increased intracardiac pressures causing limited ventricular filling and decreased cardiac output  Three most common causes are neoplastic disease, idiopathic pericarditis and renal failure II. CLINICAL MANIFESTATIONS  Dyspnea, orthopnea and fatigue  Beck’s triad: hypotension, neck vein engorgement and muffled heart sounds  Tachycardia, tachypnea and pulsus paradoxus (>10 mmHg decrease in SBP during inspiration) A. Diagnostics for Cardiac Tamponade DIAGNOSTICS 12-L ECG  Chest Radiograph  2D Echocardiography  

COMMENTS/EXPECTED FINDINGS Low voltage QRS complexes with electrical alternans Multi-chambered cardiomegaly “water-bottle” sign Large pericardial effusion Right atrial and right ventricular diastolic collapse

B. Differentials for Cardiac Tamponade CHARACTERISTIC CARDIAC TAMPONADE Clinical Features Pulsus Paradoxus +++ Jugular Veins Prominent y-descent +++ Prominent x-descent Kussmaul’s sign Third Heart Sound Pericardial Knock -









++ ++ +++ ++

+ +++ + + -

+ + +++ + -

+++ ++ + -


Electrocardiogram Low ECG voltage Electrical Alternans Echocardiography Thick pericardium Pericardial effusion RV size Exaggerated Respiratory Variation CT-MRI Thick pericardium Equalization of Diastolic Pressure Cardiac Biopsy Helpful?

++ ++

++ -

++ -


++ +

+++ Usually small +++

+++ Usually normal +++

Usually normal -

++ Enlarged +++



+++ +++


++ ++






CMP: Cardiomyopathy; RVMI: right ventricular myocardial infarction

IV. MANAGEMENT  Emergency pericardiocentesis  Tube pericardiostomy with pericardial window (for recurrent, infectious, malignant and other chronic causes)


Heterogenous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually (but not invariably) exhibit inappropriate ventricular hypertrophy or dilatation and are due to a variety of causes that frequently are genetic  It excludes cardiac dysfunction that results from other structural heart diseases such as CAD, valvular disease or severe hypertension DILATED RESTRICTIVE HYPERTROPHY CARDIOMYOPATHY CARDIOMYOPATHY CARDIOMYOPATHY Cardiac enlargement, Endomyocardial scarring or Disproportionate resulting in impaired systolic myocardial infiltration hypertrophy, typically Pathophysiology function, HF, arrhythmia, resulting in restriction of involving the interventricular emboli ventricular filling septum more than the free wall Ejection Fraction Usually 60% LV Dimension Dilated >60mm >60mm (may be decreased) Often decreased LV Wall Thickness Decreased Normal or increased Markedly increased Atrial Size Increased Increased; may be massive Increased Valvular Regurgitation Related to annular dilation Related to endocardial Related to valve-septum involvement interaction Common First Symptoms Exertional intolerance Exertional intolerance, fluid Exertional intolerance; may retention early have chest pain Congestive Symptoms Left before right Right often predominates Left-sided congestion may develop late Viral, parasitic Amyloidosis Most common abnormality Common examples Peripartum Loeffler’s found at autopsy in young Alcohol, MAP, cocaine Endomyocardial competitive athletes who die Chemotherapy suddenly Normal LVEF: > 50% Normal LV dimension: < 55mm


DEFINITION AF in a patient 7 days or require termination by cardioversion Lasted for > 1 year when it is decided to adopt a rhythm control strategy Presence of arrhythmia is accepted by the patient – rhythm control interventions are not pursued

II. STROKE PREVENTION IN AF  Efficacy of stroke prevention with aspirin is weak and the risk of major bleeding with aspirin is not significantly different from oral anticoagulants (OACs)  Usually has two scoring systems: o CHA2DS2-VASc Score: to determine the risk of having a stroke in the presence of AF o HAS-BLED: to determine the risk of bleeding (since patients with AF will be given anticoagulants) A. CHA2DS2-VASc Score  Estimates the risk of ischemic stroke in patients with non-rheumatic / non-valvular atrial fibrillation  Better than CHADS2 in identifying “truly low risk” patients with AF  Components and corresponding points: VARIABLE SCORE (POINTS) C Congestive HF / left ventricular dysfunction 1 H Hypertension (>140/9 mmHg) 1 A2 Age > 75years 2 D Diabetes 1 S2 Prior stroke / TIA / thromboembolism 2 V Vascular disease (prior MI, PAD, aortic plaque) 1 A Age 65-74 1 Sc Female sex 1

RISK 0: 0% 1: 1.3% 2: 2.2% 3: 3.2% 4: 4.0% 5: 6.7% 6: 9.8% 7: 9.6% 8: 12.5% 9: 15.2%

B. HAS-BLED Score  Bleeding risk score to aid in decision-making for thromboprophylaxis (to balance the risk of stroke versus risk of major bleeding)  High risk for bleeding: HAS-BLED score > 3 (regular monitoring and correction of potentially reversible risk factors for bleeding) VARIABLE SCORE (POINTS) Hypertension (SBP > 160 mmHg) 1 Abnormal renal / liver function 1  Renal: Chronic dialysis or renal transplantation or creatinine > 200 umol/L 1  Liver: CLD, bilirubin >2x ULN with AST / ALT / Alk Phos >3x ULN Previous Stroke 1 Bleeding history or predisposition (bleeding diathesis, anemia, etc) 1 Labile INR (unstable or high INR) 1 Elderly (age >65) 1 Use of Drugs predisposing to bleeding (e.g., antiplatelets, NSAIDs) 1 Alcohol use (>8 drinks per week) 1 CLD: Chronic Liver Disease ULN: Upper Limit of Normal

III. MANAGEMENT OF ATRIAL FIBRILLATION A. Drugs for Rate Control:  B-blockers: metoprolol, bisoprolol, atenolol, esmolol, propranolol, carvedilol  Non-dihydropyridine CCB: verapamil, diltiazem  Digitalis / Digoxin  Others: amiodarone, dronedarone


B. Pharmacological Cardioversion:  If with structural heart disease: Amiodarone  If without structural heart disease: Flecainide, Ibutilide, Propafenone C. Electrical Cardioversion:  Used for patients with recent-onset AF (1 stroke risk factor(s) provided there are no contraindications  Superior to antiplatelets in preventing stroke  Usual INR target: 2.0-3.0 B. Non-Vitamin K Oral Anticoagulants (NOACs)  Non-inferior to warfarin, but with better safety profile  Broadly preferably to warfarin in the vast majority of patients with non-valvular AF  Assessment of renal function is mandatory for all NOACs, especially for Dabigatran  Do not require dose adjustment on the basis of a specific coagulation test (in contrast to INR in warfarin)  Do not have specific antidotes, and management of bleeding is supportive  Not recommended in patients with severe renal impairment (creatinine clearance < 30 mL/min) DRUG MECHANISM OF ACTION DOSE  Oral direct thrombin inhibitor  150 mg BID  150 mg BID superior to warfarin with same risk as warfarin to cause  110 mg BID for> age > 80, Dabigatran major bleeding concomitant interacting drugs, HAS-BLED > 3, creatinine  110 mg BID non-inferior to warfarin clearance 30-40 mL/min with fewer major bleeds (compared to warfarin)  Oral direct factor Xa inhibitor  20 mg OD Rivaroxaban  Non-inferior to warfarin in  15 mg OD if: HAS-BLED > 3, preventing stroke creatinine clearance 30-49 mL/min  5 mg BID Apixaban  Oral direct factor Xa inhibitor  2.5 mg BID if : age > 80 years, weight < 60 kg, or creatinine > 133 umol/L

PERIPHERAL ARTERY DISEASE (PAD) I. ETIOPATHOGENESIS  Clinical disorder characterized by stenosis or occlusion in the aorta or arteries of the limbs  Atherosclerosis is the leading cause of PAD in patients >40 years old II. CLINICAL MANIFESTATIONS A. History and Symptoms  More than half of patients with PAD are actually asymptomatic, though some may present with slow gait  Most common symptoms: intermittent claudication (pain, ache, cramp, numbness, or sense of fatigue in the muscles which occurs during exercise and is relieved by rest)  Other symptoms are rest pain or feeling of coldness or numbness in the feet and toes


B. Physical Examination  Decreased or absent pulses distal to obstruction  Bruits over narrowed artery  Muscle atrophy, hair loss, thickened nails, smooth and shiny skin  Reduced skin temperature  Pallor, cyanosis,, ulcers or gangrene III. DIAGNOSIS DIAGNOSTICS  ABI Assessment by Doppler   Other Non-Invasive Tests   

COMMENTS / EXPECTED FINDINGS ABI: ratio of ankle to brachial artery pressure o >1.0: normal individuals o 10% o FEV1 increases by >12% and 200 mL from baseline after 4 weeks of anti-inflammatory treatment  PEF variability is calculated from twice daily readings (best of 3 each time), averaged over 1-2 weeks: Day’s highest PEF – Day’s lowest PEF PEF Variability =

mean of the day’s highest and lowest PEF

III. DIAGNOSIS A. Classification of Asthma Severity by Level of Control CONTROLLED (all of the following) Daytime Symptoms None (2x or less/week) Limitation of Activities None Nocturnal Symptoms None (Awakening) Need for Reliever None (2x or less/week) Lung Function Normal Exacerbation None B. Asthma Phenotypes PHENOTYPE

Allergic Asthma

    

PARTYLY CONTROLLED (any measure present) >2x/week Any Any >2x/week 120 bpm O2 saturations 90-95% 50% predicted or best < 50% predicted or best Flow (PEF) SABA Transfer to acute care facility Treatment Ipratropium bromide SABA Prednisolone 1mg/kg PO Ipratropium bromide


Controlled oxygen

Controlled oxygen Oral or IV corticosteroids Consider IV magnesium Consider high dose ICS

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) I. ETIOPATHOGENESIS  Characterized by expiratory airflow limitation that is not fully reversible (hallmark: airflow obstruction)  Unusual in the absence of smoking or prior history of smoking, except for patients with A1-antitrypsin deficiency  Elastase-Antielastase Hypothesis: remains a prevailing mechanism for its pathophysiology A. The Pathological Changes include:  Chronic inflammation  Increased numbers of specific inflammatory cell types in different parts of the lung  Structural changes resulting from repeated injury and repair B. Encompasses the Following Conditions:  Emphysema: anatomically-defined condition characterized by enlargement and destruction of alveoli “pink puffers”)  Chronic bronchitis: clinical condition characterized by chronic cough and phlegm (“blue bloaters”)  Small airways disease: condition where bronchioles are narrowed II. CLINICAL MANIFESTATIONS CARDINAL SYMPTOMS   Most common symptoms: Cough, sputum production, exertional dyspnea

     

SIGNS May be normal in early stages Pink puffers (predominantly emphysema): thin, non-cyanotic, prominent use of accessory muscles Blue bloaters (predominantly chronic bronchitis): heavy and cyanotic “Tripod position”: to facilitate use of accessory muscles Signs of hyperinflation: barrel chest, enlarged lung volumes on percussion (hyperresonance) Others: pursed-lip breathing, expiratory wheezing, systemic wasting, weight loss Signs of cor pulmonale (bipedal edema, ascites) in severe cases Clubbing is not a sign of COPD and should alert the clinician to other causes of clubbing

III. DIAGNOSIS  A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and a history of exposure to risk factors for the disease  Risk factors: tobacco smoke (including popular local preparations), smoke from home cooking and heating fuels, occupational dusts and chemical DIAGNOSTIC TEST COMMENTS/EXPECTED FINDINGS  Required to make the diagnosis  Post-bronchodilator FEV1/FVC 80% predicted sputum production Mild  Patient unaware that lung function is abnormal  Chronic cough and sputum production GOLD 2 FEV1 50 to 25/min Exclusion Criteria (any may be present)  Respiratory arrest  Cardiovascular instability  Change in mental status; uncooperative patient  High aspiration risk  Viscous or copious secretions  Recent facial or gastroesophageal surgery  Craniofacial trauma  Fixed nasopharyngeal abnormalities  Burns  Extreme obesity


Indications  Unable to tolerate NIV or NIV failure  Severe dyspnea with use of accessory muscles and paradoxical abdominal motion  RR >35/min  Life-threatening hypoxemia  Severe acidosis (pH 60 mmHg)  Respiratory arrest  Somnolence, impaired mental status  Cardiovascular complications  Other complications (e.g., metabolic abnormalities, sepsis, pneumonia, pulmonary embolism, barotrauma, massive pleural effusion)

D. Discharge Criteria  Inhaled beta-agonist use no more frequent than q4h  Patient is able to walk across room  Patient able to eat and sleep without frequent awakening by dyspnea  Patient has been clinically stable for 12-24 hours  ABG have been stable for 12-24 hours  Patient (or home caregiver) fully understands the use of meds  Follow-up plans have been finalized and home care arrangements have been completed

COMMUNITY-ACQUIRED PNEUMONIA (CAP) I. ETIOPATHOGENESIS  Lower respiratory tract infection (pulmonary parenchyma) acquired in the community within 24 hours to less than 2 weeks  Results from the proliferation of microbial pathogens at the alveolar level and the host’s response to those pathogens  Most common access of microorganisms to the lower respiratory tract is through aspiration from the oropharynx  Classic pneumonia (lobar pneumococcal) evolves through a series of changes




   

Red Hepatization

Gray Hepatization

 

Resolution (Final Phase)

DESCRIPTION Initial phase with the presence of a proteinaceous exudate and often of bacteria in the alveoli Erythrocytes in the cellular intraalveolar exudate Neutrophil influx is more important from the standpoint of host defense Bacteria are occasionally seen in pathologic specimens No new erythrocytes are extravasating and those already present have been lysed and degraded The neutrophilis the predominant cell, fibrin deposition is abundant and bacteria have disappeared This phase corresponds with successful containment of the infection and improvement in gas exchange Macrophage reappears as the dominant cell type in the alveolar space and the debris of neutrophils, bacteria and fibrin has been cleared, as has the inflammatory response

II. CLINICAL MANIFESTATIONS  Commonly presents with acute cough, abnormal vital signs of tachypnea, tachycardia, and fever with at least one abnormal chest finding of diminished breath sounds, rhonchi, crackles or wheezes III. DIAGNOSIS A. Classification and Disposition LOW-RISK CAP Stable  RR 30/min  PR >12bpm  Temp > 40oC or 7 mmol/L (19 mg/dL) R Respiratory rate > 30 bpm B Blood pressure 65 years old

Interpretation:  0-1: treat as outpatient  2: admit patient  >3: consider ICU admission


VI. ASSESSING RESPONSE TO THERAPY A. Response to therapy is expected within 24-72 hours of initiating treatment:  Temperature, RR, HR, BP, sensorium, O2 saturation, and inspired oxygen concentration should be monitored to assess response to therapy  A patient is considered to have responded to treatment if: o Fever decreases within 72 hours; o Temperature normalizes within 5 days; and, o Respiratory signs, particularly tachypnea, return to normal  Follow-up cultures of blood and sputum are not indicated for patients who are responding to treatment B. De-escalation of antibiotic therapy once the patient is improving, stable and has a functioning GI tract:  Resolution of fever more than 24 hours  Less cough and resolution of respiratory distress (normalization of RR)  Improving WBC count, no bacteremia  Etiologic agent is not a high-risk (virulent/resistant) pathogen (e.g. Legionella, S. aureus, or gram-negative enteric bacilli)  No unstable comorbid condition or life-threatening complications such as MI, CHF, complete heart block, new atrial fibrillation, supraventricular tachycardia, etc.  No sign of organ dysfunction such as hypotension, acute mental changes, BUN to creatinine ratio of >10:1, hypoxemia, and metabolic acidosis  Patient is clinically hydrated, taking oral fluids and is able to take oral medications C. Duration of Treatment ETIOLOGIC ORGANISMS Most bacterial pneumonias Enteric Gram-negative pathogens, S. aureus, and P. aeruginosa Mycoplasma and Chlamydophila Legionella

DURATION OF TREATMENT (days) 5-7 14 10-14 14-21

D. Failure to improve after 72 hours of treatment is an indication of reassessment  Incorrect diagnosis or presence of complicating noninfectious condition (e.g., pulmonary embolism, CHF, vasculitis, MI)  A resistant microorganism or an unexpected pathogen that is not covered by the antibiotic of choice  Antibiotic is ineffective or causing an allergic reaction  Impaired local or systemic host defenses (e.g., aspiration, endobronchial obstruction, bronchiectasis)  Local or distant complications of pneumonia (e.g., parapneumonic effusion, empyema, lung absecess, ARDS, metastatic infection, endocarditis)  Overwhelming infection  Slow response in the elderly patient (S. pneumoniae and L. pneumophila)  Exacerbation of co-morbid illness  Nosocomial superinfection E. Hospital Discharge  In the absence of any unstable coexisting illness or other life-threatening complication, the patient may be discharged once clinical stability occurs and oral therapy is initiated 1. During the 24 hours before discharge, the patient should have the following characteristics:  Temperature of 36-37.5oC  Pulse 90 mmHg  Blood O2 saturation >90%  Functioning GI tract 2. Repeat Chest Radiograph  Not needed in patients who are clinically improving  Recommended during a follow-up visit, approximately 4 to 6 weeks after hospital discharge


HEALTH CARE-ACQUIRED PNEUMONIA (HCAP) I. ETIOPATHOGENESIS  Transition between classic CAP and typical HAP A. Ventilator-Associated Pneumonia (VAP)  The greatest difference between VAP and HCAP/HAP is the return to dependence on expectorated sputum for a microbiologic diagnosis of VAP, which is further complicated by frequent colonization by pathogens in patients with HAP or HCAP  Common pathogenic mechanisms include oropharyngeal colonization with pathogenic bacteria, cross-infection from other colonized patients, large volume aspiration, microaspiration around ET tub and altered lower respiratory host defenses  Clinical manifestations: same in VAP as with any other forms of pneumonia: fever, leukocytosis, increase in secretions, and pulmonary consolidation on PE, along with a new or changing radiographic infiltrate NON-MDR PATHOGENS MDR PATHOGENS Streptococcus pneumoniae Pseudomonas aeruginosa Other Streptococcus spp. MRSA Haemophilius 95nfluenza Acinetobacter spp. Antibiotic-resistant Enterobacteraceae MSSA Antibiotic-sensitive Enterobacteriaceae Enterobacter spp. Escherichia coli ESBL-positive strains Klebsiella pneumoniae Klebsiella spp. Proteus spp. Legionella pneumophila Enterobacter spp. Burkholderia cepacia Serratia marcescens Aspergillus spp. B. Hospital-Acquired Pneumonia (HAP)  HAP in non-intubated patients, both inside and outside the ICU, is similar to VAP save for the higher frequency of non-MDR pathogens and better underlying host immunity in non-intubated patients  the lower frequency of MDR pathogens allows monotherapy in a majority of HAP cases  The only pathogens that may be more common in the non-VAP population are the anaerobes (due to a higher risk of macroaspiration)  More difficult to obtain lower respiratory samples appropriate for culture in non-intubated patients II. CLINICAL CONDITIONS ASSOCIATED WITH MDR PATHOGENS IN HCAP  Hospitalization for > 48 hours  Hospitalization for > 2 days in prior 3 months  Nursing home or extended-care-facility residence  Antibiotic therapy in preceding 3 months  Chronic dialysis  Home infusion therapy  Home wound care  Family member with MDR infection III. MANAGEMENT  Once an etiologic diagnosis is made, broad-spectrum empirical therapy can be modified to address the known pathogen specifically  Empirical antibiotic treatment of HCAP WITHOUT RISK FACTORS FOR MDR PATHOGENS WITH RISK FACTIRS FOR MDR PATHOGENS Standard recommendation is treatment with three antibiotics: two directed at P. aeruginosa and one at Majority can be treated with a single agent MRSA A beta-lactam: Ceftriaxone 2g IV q24 Moxifloxacin 400 mg IV q24  Ceftazidime 2g IV q8 or Cefepime 2g IV q8-12 Ciprofloxacin 400 mg IV q8 or Levofloxacin 750 mg IV q24  Piperacillin/tazobactam 4.5g IV q6, Imipenem Ampicillin/sulbactam 3g IV q6 500 mg IV q6 or 1g IV q8, plus Ertapenem 1g IV q24


A second agent against gram-negative bacteria:  Gentamicin or Tobramycib 7 mg/kg IV q24 or Amikacin 20 mg/kg IV q24, or  Ciprofloxacin 400 mg IV q8 or Levofloxacin 750 mg IV q24, plus An agent against gram-positive bacteria:  Linezolid 600 mg IV q12, or  Vancomycin 15mg/kg, up to 1 g IV q12

PULMONARY TUBERCULOSIS (PTB) I. ETIOPATHOGENESIS  Caused by Mycobacterium tuberculosis  Most common site for the development of TB is the lungs (85% of patients)  Most commonly transmitted from person with infectious PTB to others by droplet nuclei, which are aerosolized by coughing, sneezing or speaking. Aerosolized droplets are 1-5 µm in diameter. A single cough can generate 3000 infective droplets, with as few as 10 bacilli needed to initiate infection  Most infectious patients: those with cavitary pulmonary disease and laryngeal TB  Typical TB lesion: epitheloid granuloma with central caseation necrosis II. CLINICAL MANIFESTATIONS  In the Philippines, cough of two weeks or more should lead to high index of suspicion for PTB  Cough may be accompanied by night sweats, weight loss, unexplained fever and chills, chest pain, fatigue and body malaise  Absence of fever does not exclude TB  Physical findings are of little utility in PTB A. General Classification of Tuberculosis CLASSIFICATION   Presumptive TB   

DEFINITIONS Cough of at least 2 weeks in an adult (age > 15 y/o) A child (< 15 y/o) fitting criteria for TB Radiologic imaging suggestive of tuberculosis Any person who presents with symptoms or signs suggestive of TB Cough of any duration in a high risk individual or a close contact of an active TB case Definite case  A patient with MTB complex identified from a clinical specimen either by culture or by a newer method such as molecular line probe assay New case  Patient who never had treatment for TB or who has taken anti-TB medications for < 1 month Retreatment case (patient previously treated with anti-TB drugs for at least 1 month in the past)  Patient who was previously treated for TB, and was declared cured for has Relapse completed treatment; and is now bacteriologically or clinically diagnosed TB  Patient who was previously treated for TB, and treatment failed at the end of the most recent course: o Sputum smear or sputum culture positive at 5 months or later Treatment after failure during treatment o Clinically diagnosed in a patient in whom sputum studies cannot be done, without clinical improvement anytime during the course of treatment Treatment after lost to follow A patient who returns to treatment with positive bacteriology (smear or up (TALF) culture) or clinically diagnosed, following interruption of treatment for two months or more Previous treatment outcome  A previously treated patient whose outcome was not known or not unknown (PTOU) documented


B. Classification of Tuberculosis based on Anatomical Site Affected At least 1 (or 2) sputum specimen positive for AFB, with or without radiographic abnormalities Patient with sputum culture, Culture-positive with or without radiographic abnormalities Patient with positive sputum Rapid Diagnostic testfor MTB using a rapid positive diagnostic test (e.g. Xpert MTB/Rif) with or without radiographic abnormalities Two sputum specimens negative for AFB or MTB; but with clinical or radiologic evidence consistent with active TB and there is a decision by a physician to treat as tuberculosis Smear/culture/rapid diagnostic test from an extrapulmonary site positive for AFB A patient with histologic and/or clinical or radiologic evidence consistent with active extra-pulmonary TB and there is a decision by a physician to treat as tuberculosis Smear-positive

BacteriologicallyConfirmed Pulmonary TB


Extra-Pulmonary TB (EPTB)

BacteriologicallyConfirmed Clinically-Diagnosed

III. DIAGNOSIS DIAGNOSTICS   Sputum Microscopy for AFB

  Sputum TB Culture

 Chest Radiograph Rapid Diagnostic Test (Xpert MTB/Rif Assay)

 

COMMENTS / EXPECTED FINDINGS At least two sputum specimens should be sent Sputum collection: o Two sputum specimens of good quality shall be collected, either as frontloading (e.g., spot-spot one-hour apart) or spot-early morning specimens, based on the patient’s preference o The two specimens should be collected at most within 3 days Primarily recommended for patients at risk for drug resistance It is recommended in the following smear positive patients: o All cases of retreatment o All cases of treatment failure o All other cases of smear positive patients suspected to have one or more multi-drug resistant TB o All household contacts of patients with MDR-TB o In patients with HIV Recommended for patients suspected to have PTB whose sputum smears are negative Initiating TB treatment based on chest radiographs alone is discouraged Gene Xpert testing for the presence of Mycobacterium tuberculosis and Rifampicin resistance


Presumptive TB Cough of at least 2 years in an adult > 15 years old CXR suggestive of tuberculosis Cough of any duration in a high risk individual or close contact of an active TB case

Sputum smear microscopy


Negative or not done

Chest Radiograph If not suggestive of TB  Not TB If suggestive of TB  proceed to nest step Bacteriology confirmed TB MTB (+) Rif-sensitive Xpert MTB/Rif** MTB Negative  Not TB MTB Positive  Next step

History of previous TB treatment? No Bacteriologically confirmed TB New Case


MTB (+) Rif-Resistant

Bacteriologically confirmed TB Retreatment

Refer to PMDT$ Services for Evaluation

Clinically Diagnosed TB Retreatment

If no access to Xpert MTB/Rif: Decision of MD or TBDC+? Either “Not TB” or “Clinically Diagnosed TB”


Category I Treatment

History of previous TB treatment?

Category II Treatment (for Rif-sensitive)

If clinically diagnosed TB


Clinically Diagnosed TB New Case

*Positive: at least 1 (of 2) specimen for acid fast bacilli ** Xpert MTB/Rif: Rapid diagnostic test for the presence of Mycobacteria tuberculosis and Rifampicin resistance + TBDC: Tuberculosis diagnostic committee $ PMDT: Programmatic Management of Drug-Resistant Tuberculosis (possible MDR-TB treatment if Rifampicin Resistant TB)


IV. MANAGEMENT A. Treatment Regimen for TB CATEGORY 



 


IIa 

Drug Resistant TB



New pulmonary TB (bacteriologicallyconfirmed or clinically diagnosed) New extra-pulmonary TB (bacteriologicallyconfirmed or clinically-diagnosed), except CNS / bones or joints New extra-pulmonary TB (CNS / bones or joints) Pulmonary or extra-pulmonary, previously treated drug-susceptible TB (whether bacteriologically-confirmed or clinicallydiagnosed), except CNS / bones or joints o Relapse o Treatment after failure o Treatment after lost to follow-up (TALF) o Previous treatment outcome unknown (PTOU) o Other Extra-pulmonary (CNS / bones or joints), previously treated, drug susceptible TB (whether bacteriologically-confirmed or clinically-diagnosed) Standard regime drug-resistant (SRDR): rifampicin resistant TB or multi-drug resistant TB XDR TB regimen: extensively drugresistant TB


4 HR or 4HRE*


10 HR

2 HRZES and 1 HRZE


2 HRZES and 1 HRZE


Individualized based on previous treatment courses and drug sensitivity testing

*if with cavitary disease, give streptomycin IM alternate days (60 days) instead of ethambutol # based on the WHO guideline, in populations with known or suspected high levels of isoniazid resistance, new TB patients may receive HRE as therapy in the continuation phase as an acceptable alternative to HR

B. Drugs used for Tuberculosis DRUG DOSE (daily) Isoniazid (H/INH)

5 mg/kg, max 300 mg


Rifampicin (R)

10 mg/kg, max 600 mg

   

Pyrazinamide (Z)

25 mg/kg, max 2 g

 

Ethambutol (E)

 15 mg/kg

Inhibits fatty acid synthase and mycolic acid synthesis Excellent bactericidal activity against both intracellular and extracellular actively dividing MTB Bacteriostatic against slowly dividing organisms Binds to and inhibits mycobacterial DNA-dependent RNA polymerase thereby blocking RNA synthesis Has both intracellular and extracellular bactericidal activity, both in dividing and non-dividing MTB Also has sterilizing activity Most active antimycobacterial agent available and therefore the cornerstone of first-line TB treatment Exact mechanism is unclear (fatty acid synthetase-) may be the primary target) More active against slowly replicating organisms than against actively replicating organisms Active only in acidic environment (pH0.5 Pleural fluid LDH/serum LDH >0.6 Pleural fluid LDH more than two-thirds normal upper limit for serum These criteria misidentify -25% of transudates as exudates. If one or more of the exudative criteria arte met and the patient is clinically thought to have a condition producing a transudative effusion, the difference between the protein levels in the serum and the pleural fluid should be measured. If this gradient >31 g/L, the exudative categorization by these criteria can be ignored because almost all such patients have transudative pleural effusion

B. Common causes of pleural effusion Transudative Pleural Effusions   Effusion due to Heart Failure

Cirrhosis Other Transudative Effusions Exudative Pleural Efusions Parapneumonic Effusion Bacterial Pneumonia

    

Most common cause of pleural effusion Diagnostic thoracentesis should be performed: o If effusions are not bilateral and comparable in size o If patient is febrile o If patient has pleuritic chest pain, to verify that the patient has a transudative effusion; otherwise, the heart failure is treated Pleural fluid N-terminal pro-brain natriuretic peptide (NT-proBNP) >1500 pg/mL is virtually diagnostic Liver cirrhosis may give rise to pleural effusion Usually on the right side (passage of fluid from abdomen through diaphragm) Nephritic syndrome, myxedema, urinothorax Pulmonary embolism (may also be exudative) Most common cause of exudative pleural effusion (in the US)


Lung Abscess Bronchiectasis Empyema

  

     Effusion secondary to Malignancy

   

Effusion secondary to Pulmonary Embolism

   

Tuberculosis Pleuritis      Hemothorax 

Presents with acute febrile illness consisting of chest pain, sputum production and leukocytosis If free fluid separates the lung from the chest wall by >10mm, a therapeutic thoracentesis should be performed The following factors indicate the need for a more invasive procedure (e.g., CTT insertion) o Loculated pleural fluid o Pleural fluid pH 200 mL/h, consider thoracoscopy or thoracotomy



Presence of gas in the pleural space


  

Secondary PTX

 

Traumatic PTX

Tension PTX

ETIOLOGY/PATHOGENESIS Occurs in the absence of underlying lung disease Usually due to rupture of apical pleural blebs Occurs almost exclusively in smokers (those with subclinical disease) Occurs in the presence of underlying lung disease Mostly due to COPD (but have been reported in all lung disease) Penetrating or non-penetrating chest injuries Iatrogenic PTX is a subtype which is increasingly becoming more common


Simple aspiration: initial treatment If lung does not expand or PTX recurs, thoracoscopic stapling of blebs and pleural abrasion

Tube thoracostomy or thoracoscopy or thoracotomy with bleb stapling and plural abrasion If patient refuses surgery, pleurodesis is an option Tube thoracostomy unless very small and can be managed with supplemental oxygen or aspiration If hemopneumothorax: two chest tubes directed at each lesion Medical emergency Large-bore needle should be inserted into the pleural space through the 2nd anterior ICS and should be left in place until a thoracostomy tube can be inserted

    

Pressure in the pleural

SUPERIOR VENA CAVA (SVC) SYNDROME I. ETIOPATHOGENESIS  Clinical manifestation of superior vena caval obstruction with severe reduction in venous return from the heart, neck and upper extremities  Most common etiologies are lung CA, lymphoma and metastatic tumors o Lung CA (small cell and squamous cell) accounts for 85% of all cases of malignant origin o Malignant lymphoma is the leading cause of SVCs in adults  The increasing use of intravascular devices has led to increasing prevalence of benign causes of SVC  Other benign causes: aneursyms, thyromegaly, thrombosis, fibrosing mediastinitis, histoplasmosis or Behcet’s syndrome II. CLINICAL MANIFESTATIONS  SVCs usually present with neck and facial swelling (especially around the eyes), dyspnea and cough  Other symptoms are hoarseness, tongue swelling, headaches, nasal congestion, epistaxis, hemoptysis, dysphagia, pain, dizziness, syncope and lethargy which are aggravated by bending forward or lying down  PE findings include dilated neck veins, increased number of collateral veins over the anterior chest wall, cyanosis and edema of the face, arms and chest  More severe cases present with proptosis, glossal and laryngeal edema, obtundation and signs of cerebral edema  Cardiorespiratory symptoms may occur at rest when significant airway and vascular obstruction occurs  Rarely, esophageal varices may develop III. DIAGNOSIS OF SVC SYNDROME DIAGNOSTICS  Chest Radiography 

COMMENTS / EXPECTED FINDINGS Most significant finding is widening of the superior mediastinum (more commonly on the right side) Pleural effusion occurs in 25% (often on the right side) - majority are


Chest CT Chest MRI Invasive Procedures (e.g., broncoscopy, percutaneous core needle biopsy, mediastinoscopy and thoracotomy)

exudative and occasionally chylous May be normal in some cases Provides the most reliable view of the mediastinal anatomy Diminished or absent opacification of central venous structure with prominent collateral venous circulation No advantages over CT

Necessary for etiologic diagnosis / histologic diagnosis

  

IV. MANAGEMENT  Upper airway obstruction demands emergent therapy: o Diuretics with low salt diet o Head elevation o Oxygen support o Glucocorticoids for lymphoma (no benefit in lung CA)  Radiation therapy is the primary treatment for SVCs caused by NSCLC and other metastatic solid tumors  Chemotherapy is effective when the underlying CA is SCLS of the lung, lymphoma or germ cell tumor  Recurrent SVC may be palliated with use of intravascular self-expanding stents (however, may precipitate heart failure and pulmonary edema)  The mortality with SVC does not relate to caval obstruction but rather to underlying cause


CHAPTER 4 CRITICAL CARE I. Shock in the Intensive Care Setting 1. 2. 3. 4.

Overview of the Types of Shock Cardiogenic Shock Sepsis and Septic Shock Other Forms of Shock

II. Common Conditions Encountered in the ICU 1. 2. 3.

Respiratory Failure Acute Respiratory Distress Syndrome Venous Thromboembolism

III. Overview of Mechanical Ventilation 1. 2. 3.

Non-Invasive Ventilation (NIV) Basic Modes of Mechanical Ventilation Oxygen Delivery, Spontaneous Breathing Trial and Weaning







Cardiogenic Shock

Septic Shock Hyperdynamic phase (Early) Hypodynamic phase (Late) Hypovolemic Shock

↑↓ ↑↓

↑ ↓

↓ ↑

↓ ↓ ↓

↓ ↓ ↓

↑ ↓ ↓

Hypoadrenal Shock Neurogenic Shock CVP: central venous pressure (N: 3-10 mmHg) PCWP: pulmonary capillary wedge pressure (N: 4-12 mmHg) CO: cardiac output (N: 4-8 L/min) SVR: systemic vascular resistance (N: 700-1600 dynes.s/cm2)

CARDIOGENIC SHOCK I. ETIOPATHOGENESIS  Characterized by systemic hypoperfusion due to severe depression of cardiac index (100 mmHg:  Furosemide IV 0.5-1 mg/kg  NTG 10-20 mcg/min IV  Morphine IV 2-4 mg  Oxygen/intubation as needed  NTG SL then 10-20 mcg/min IV if SBP 70-100 mmHg and no signs/symptoms of shock: If with bradycardia or SBP >100 mmHg tachycardia:  Dobutamine 2-20  Norepinephrine 0.5-30 mcg/min First Line of  Manage accordingly mcg/kg/min IV IV or Dopamine 5015 Action based on ACLS mcg/kg/min IV if SBP 100 mmHg and not less than 20 mmHg below baseline: consider ACE-inhibitors such Action as Captopril 1-6.25 mg  The following should be considered in non-hypovolemic shock Third Line of o Diagnostics: pulmonary artery catheter, echocardiography, angiography for MI/ischemia Action and other additional diagnostic studies o Therapeutics: intra-aortic balloon pump, reperfusion/revascularization

SEPSIS AND SEPTIC SHOCK I. ETIOPATHOGENESIS  TNF-alpha is a central mediator  Intravascular thrombosis is the hallmark of the local inflammatory response


Endothelial injury is the major mechanism of multi-organ dysfunction

II. DIAGNOSIS AND DEFINITIONS A. Bacteremia Versus Septicemia Bacteremia Presence of bacteria in blood, as evidenced by positive blood culture Septicemia Presence of microbes or their toxins in blood B. Definition in Terms SYNDROME  Signs of Possible Harmful Systemic Response (SIRS)   Sepsis (or Severe Sepsis)

 Septic Shock Refractory Septic Shock Multiple-Organ Dysfunction Syndrome (MODS)

  

DEFINITION Two or more of the following conditions (may have a noninfectional etiology): o Fever (oral temperature >38oC) or hypothermia (24 breaths/min) o Tachycardia (HR >90 bpm) o Leukocytosis >12,000 or leukopenia 10% bands The harmful host response is infection Sepsis with one or more signs of organ dysfunction: o CVS: arterial SBP < 90 mmHg or MAP 8 mmHg

III. MANAGEMENT A. Initial Resuscitation (first 6 hours)  CVP 8-12 mmHg Resuscitation Goals  MAP > 65 mmHg  Urine output >0.5 mL/kg/hour  Obtain appropriate blood cultures  Broad-spectrum IV antibiotics with good penetration into presumed source of infection Antibiotic Therapy  Combination therapy in Pseudomonas infections and neutropenic patients for at least 3-5 days and de-escalation following susceptibility studies  Duration of therapy typically 7-10 days; longer if response is slow or there are undrainable foci of infection or immunologic deficiencies B. Hemodynamic Support and Adjunctive Therapy Fluid Therapy  Crystalloids or colloid with target CVP of 8-12 mmHg (>12 mmHg if mechanically ventilated) Vasopressors  Maintain MAP >65 mmHg  Norepinephrine and Dopamine are the initial vasopressors of choice Inotropic Therapy  Dobutamine in patients with myocardial dysfunction as supported by elevated cardiac filling pressures and low CO Steroids  Consider IV hydrocortisone for adult septic shock when hypotension responds poorly to adequate fluid resuscitation and vasopressors


C. Other Supportive Therapy

Blood Transfusion

RBC transfusion if hemoglobin is:  3 points

(Well’s Scoring) PULMONARY EMBOLISM Parameter Signs and symptoms of DVT Alternative diagnosis less likely than PE HR >100bpm Immobilization >3 days; surgery within 4 weeks Prior PE or DVT Hemoptysis Cancer

Score 3 3 1.5 1.5 1.5 1 1

High clinical likelihood of PE: >4

B. Approach to Diagnosis 1. Request for a D-Dimer (rule out test) if:  Likelihood for DVT is low  Likelihood for PE is not high 2. Request for an Imaging Test if:  Likelihood for DVT is not low  Likelihood for PE is high C. Diagnostics for PE DIAGNOSTICS Plasma D-dimer ELISA


High sensitivity for PE Useful rule-out test: patients with normal D-dimer do not have PE


It is not specific as levels can increase with MI, pneumonia, sepsis, cancer, postoperative state, 2nd and 3rd trimester of pregnancy Both PO2 and PCO2 may be decreased in PE Most common abnormality in PE is T-wave inversion in leads V1 to V4 Most frequently cited abnormality in PE (in addition to sinus tachycardia): S1 Q3 T3 o S wave in Lead I o Q wave in Lead III o Inverted T wave in Lead III May be increased in RV microinfarction

    

Westermark’s sign: focal oligemia Hampton’s Hump: peripheral wedged-shaped density above the diaphragm Palla’s Sign: enlarged right descending pulmonary artery Principal imaging test for the diagnosis of PE Can image small peripheral emboli

Lung scanning

 


Pulmonary angiography

Second-line diagnostic test for PE High probability scan for PE: two or more segmental perfusion defects in the presence of normal ventilation McConnell’s Sign: hypokinesis of the RV free wall with normal motion of the RV apex (best known indirect sign of PE on transthoracic echo) Definitive diagnosis of PE depends upon visualization of an intraluminal filling defect in more than one projection


  


Cardiac Biomarkers CXR Chest CT Scan with IV Contrast (high-resolution)

IV. MANAGEMENT OF VENOUS THROMBOEMBOLISM (DVT AND PE) A. Anticoagulation  Foundation of successful treatment of DVT and PE  Parenteral agents are continued as a transition or bridge to stable, long-term ANTICOAGULANT REMARKS Parenteral Anticoagulation  Binds and accelerates activity of antithrombin, thus preventing additional thrombus formation & permitting Unfractioned Heparin endogenous fibrinolytic mechanisms to (UFH) lyse the clot that has already formed  Major advantage: short half-life  Major disadvantage: repeated sampling for PTT and dose adjustment (every 4-6 hours) Low Molecular Weight  No monitoring or dose adjustment Heparin (LMWH) needed, unless obese or has CKD Fondarparinux  Anti-Xa pentasaccharide Oral Anticoagulants  Vitamin-K antagonist which prevents carboxylation activation of factors II, VII, IX, X  Full effect requires 5 days Warfarin  Overlapping UFH, LMWH, or fondaparinux with warfarin for at least 5 days can counteract early procoagulant effect of unopposed warfarin  Monitor prothrombin time (PT) with a target INR 2.5 (range of 2.0 to 3.0)  Direct thrombin inhibitor Dabigatran  Indicated for DVT and PE in those who have been treated with a parenteral

anticoagulation with warfarin DOSE FOR VTE

 IV bolus 80 units/kg, then 18 units/kg/hour (maintain PTT ratio 1.2-2.5x normal)

 1 mg/kg q12 SC  0.5mg/kg if CrCl 2x normal)


B. Fibrinolysis / Thrombolysis  The only FDA-approved indication for PE fibrinolysis is massive pulmonary embolism  Rapidly reverses right heart failure and may result in a lower rate of death and recurrent PE  Preferred agent: Recombinant Tissue Plasminogen Activator (r-tPA) C. Other Modalities  Inferior vena cava (IVC) filters  Pulmonary embolectomy  Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension  Maintenance of adequate circulation (for patients with massive PE and hypotension)  Graduated compression stockings (30-40 mmHg) for DVT (if without significant peripheral arterial disease)  Emotional support




Provided by using a tight fitting mask or nasal mask Highly effective in patients with acute exacerbations of COPD Uses bilevel positive airway pressure ventilation (“BiPAP”) If there are contraindications to NIV, invasive ventilation should be used (e.g., may require intubation)

II. CONTRAINDICATIONS FOR NIV  Cardiac or respiratory arrest  Severe encephalopathy  Severe GI bleed  Hemodynamic instability  Acute coronary syndrome  Facial surgery or trauma  Upper airway obstruction  High-risk aspiration and/or inability to protect airways  Inability to clear secretions

NON-INVASIVE VENTILATION (NIV) I. ASSIST/CONTROL MODE (A/C MODE)  The patient breathes at his own rate and the ventilator senses the inspiratory effort and delivers a preset tidal volume of each patient effort  If patient’s RR decreases at preset rate, the ventilator delivers tidal breaths at the preset rate  Since every breath is assisted, tachypnea may result in significant hypocapnia and respiratory alkalosis  Uses initial mechanical ventilation settings 1. Tidal Volume (TV) 8-10 mL/kg of ideal body weight 6 mL/kg for ALI/ARDS  “How much volume will the machine deliver?” 10-12 mL/kg for neuromuscular disease 2. Back-up Rate (BUR)  Minimum number of breaths per minute 14-22 breaths/min  Usually set 2-4 counts below the spontaneous rate (this can be adjusted depending on the desired PaCO2 or pH)  Faster RR = ↑ exhalation of CO2  ↓PaCO2 and ↑pH 3. Oxygen Concentration (FiO2)  Initial FiO2 should be 100% unless it is evident that a lower FiO2 will provide adequate oxygenation  We can start at 50% if with neuromuscular disease (e.g., 100% myasthenia gravis)  Eventually downtitrated based on desired PO2  Prolonged exposure to high oxygen concentrations is avoided as it may lead to O2 narcosis and development of more free O2 radicals 4. Inspiratory Flow Rate (IFR)  “How fast do we deliver the air?”  This is the rate at which air is delivered to the patient to achieve 40-60 L/minute the set tidal volume  Rate needs to be higher (80 L/min) in obstructive diseases such as COPD or asthma to allow for a longer time for expiration  Rate needs to be lower in patients with severe hypoxemia to


deliver air slower, prolonging inspiration time & allowing more gas exchange  An IFR lower than the patient demand will increase the work of breathing and is a common cause of patient-ventilator discordance (fighting or bucking the ventilator) 5. Inspiratory Flow Pattern (IFP)  “How do you deliver the air?”  How flow is distributed throughout the respiratory cycle  A normal person has a sine wave pattern 6. Positive End-Expiratory Pressure (PEEP)  “Physiologic PEEP” of about 5cm H2O should be added regardless of FiO2 to prevent alveolar injury due to the shearing effect of opening and closing the alveoli and therefore should be increased in ARDS  Lower PEEP is usually given to patients with hypotension as higher values increase intrathoracic pressures which can impede venous return, thereby reducing preload and subsequent CO 7. Sensitivity  Ranges anywhere from -5 to -0.5 cm H2O (pressure sensitivity) or 1 to 5 liters (flow sensitivity)  The more sensitive (e.g., 0.5 cm or 1L), the easier for the patient to trigger the ventilator which may lead to hyperventilation  The less sensitive (e.g., 5 cm or 5L), the harder for the patient to trigger the ventilator which may lead to increased work of breathing and may cause patient-ventilator dyssynchrony

Decelerating wave

5 cm H2O

-2.0 cm or 2 L a. Pressure Sensitivity  If set -1, the patient has to exert a -1cm Hg pressure for the ventilator to deliver the tidal volume b. Flow Sensitivity  If set at 1L, the patient has to exert an air flow of at least 1L  Advantageous in COPD since it affords less work of breathing for patients II. SYNCHRONIZED INTERMITTENT MANDATORY VENTILATION (SIMV)  Allows the patient to have spontaneous breaths around the intermittent synchronized ventilator breaths beyond the set respiratory rate  Patient’s contribution to minute ventilation depends on the number of spontaneous breaths & inspiratory effort EXAMPLE: Patient’s MV set on SIMV mode; BUR set at 12; patient’s actual RR is 20  Only 12 of the 20 breaths are assisted in SIMV o 12 will receive the complete (assisted) tidal volume set o 8 will receive the tidal volume depending on the patient’s effort  In contrast, in AC mode  all 20 breaths will be assisted A. A/C Mode versus SIMV Assist Work of Breathing Can be used for weaning?

   

In simple terms

A/C MODE Total Almost none No Patient breathes at his own rate Ventilator delivers a preset tidal volume with each (all effort)

   

SIMV MODE Partial Variable Yes Allows patient to breathe on his/her own if the RR exceeds the preset back-up rate


B. Advantages and Disadvantages of SIMV ADVANTAGES  Maintains respiratory muscle tone due to the continued use of the inspiratory muscles preventing disuse atrophy  There is decreased intrathoracic pressure as compared to A/C which may lead to improved hemodynamics  Useful for weaning because as the back-up rate is decreased, the patient gradually assumes the bulk of breathing


Even with the same back-up rate as the A/C, there is more work of breathing The increased work of breathing results in increased oxygen consumption which is deleterious in patients with myocardial insufficiency This mode is not useful in patients with depressed respiratory drive or impaired neurologic status

C. Selection of Ventilator Settings for the SIMV mode  Rate: initial rate should be close to the patient’s inherent rate and eventually adjusted depending on patient tolerance  VT, FiO2, IFR, IFP, PEEP selection is similar to that in A/C mode III. NEWER MODALITIES OF MECHANICAL VENTILATION Pressure Limited Ventilation Combination of Volume-Cycled and Pressure-Limited Ventilation Inverse Ratio Ventilation

  

Pressure Support Ventilation (PSV) Pressure Controlled Ventilation (PC) SIMV with PSV

 

PCV with Inverse Ratio A/C with Very Low Flow Rates

OXYGEN DELIVERY, SPONTANEOUS BREATHING TRIAL & WEANING I. OXYGEN DELIVERY  Indications: o PaO2 4 lpm B. Simple Masks  Higher potential FiO2 (provides 31-61% O2)  Flow rates between 5-10 lpm  The reservoir is the space between the mask and the patient’s face  5 lpm is needed to flush exhaled CO2 from the mask (200) and PEEP > 5 cmH2O  Cough and airway reflexes intact  No vasopressor agents or sedatives being administered


B. SBT is declared a failure and stopped if any of the following occur:  RR >35/min for >5 minutes  O2 saturation 140/min or a 20% increase or decrease from baseline  SBP 180 mmHg  Increased anxiety or diaphoresis If at the end of the spontaneous breathing trial, the rapid shallowing breathing index (RSBI) or ratio of the RR to tidal volume in liters (f/VT) is 7.25 o PO2 > 60 at FiO2 < 40%  Hemodynamic stability: HR < 140, stable BP, Hgb > 8-10  Capability to initiate inspiratory effort: GCS > 13  Acceptable electrolytes B. Additional conditions which should be met for weaning  Cessation of sedative drugs  Cessation of neuromuscular blocking agents  Absence of sepsis or marked fever  No planned general anesthesia  Adequate gas exchange  Adequate respiratory pump capacity C. Methods of Weaning METHOD   T-Piece   CPAP

  

SIMV    Pressure Support Ventilation (PSV)

DESCRIPTION Brief spontaneous breathing trials with supplemental O 2 Best tolerated by patients who have undergone M for brief periods and require little respiratory muscle reconditioning Initiated for 5 minutes/hour followed by a1-hour interval of rest Trials are increased in 5-10 min/hour increments until the patient can remain ventilator independent for 60-120 minutes, and then extubation can be attempted Mode of weaning where patient-initiated breaths are supported with preset pressure that is eventually titrated down until discontinuation Mandatory backup rate is decreased by 2 to 4 breaths per minute while monitoring blood gas parameters & RRs until < 4-6 breaths per minute are achieved Best for patients intubated for extended periods who are likely to require gradual respiratory muscle reconditioning Rates > 25/min on withdrawal of mandatory ventilator breaths generally indicate respiratory muscle fatigue and the need to combine periods of exercise with rest Shifting to PSV, CPAP, or T-Piece trial can then be attempted before extubation Mode of ventilation that is patient-triggered, pressure-limited and flow-cycled to augment spontaneous respiratory effort Well tolerated by patients who are gradually being weaned by decreasing set pressures until 4-6 cm H2O and eventual withdrawal of ventilator support


CHAPTER 5 GASTROENTEROLOGY I. Approach to Patients with Gastrointestinal Conditions 1. 2. 3. 4.

History Taking in Gastroenterology Physical Examination in Gastroenterology Gastrointestinal Endoscopy Approach to Ascites

II. Common Conditions in Gastroenterology 1. 2. 3. 4. 5. 6. 7. 8.

Peptic Ulcer Disease Gastrointestinal Bleeding Overview of Liver Disease Viral Hepatitis Alcoholic Liver Disease Liver Cirrhosis Acute Pancreatitis Surgical Causes of Right Upper Quadrant Pain



APPROACH TO PATIENTS WITH GASTROINTESTINAL CONDITIONS HISTORY TAKING IN GASTROENTEROLOGY I. COMMON GASTROINTESTINAL COMPLAINTS TERM DEFINITION Anorexia Loss or lack of appetite Early satiety Inability to eat a full meal Heartburn Retrosternal burning sensation resulting from excess gastroesophageal reflux Dysphagia Difficulty in swallowing Odynophagia Painful swallowing Diarrhea Condition in which feces are discharged from the bowels frequently and in a liquid form Constipation Condition in which there is difficulty in emptying the bowels, usually associated with hardened feces Obstipation Complete constipation with no passage of either feces or gas Tenesmus Intense urge with straining but little or no result Hematemesis Vomitus of red blood or coffee-ground material Melena Black, tarry, foul-smelling stool which usually implies bleeding proximal to the ligament of Treitz (upper GI bleed) and that blood has been in the GI tract for at least 14 hours Hematochezia Passage of bright red or maroon blood form the rectum which usually implies bleeding from the colon (lower GI bleed); may also come from an upper GI source, with rapid intestinal transit Occult GI bleeding Identified in the absence of overt bleeding by a fecal occult blood test or the presence of iron deficiency Jaundice Yellowing of the skin or sclerae, arising from obstruction in bile duct, liver disease, hemolysis, etc. Other complaints Indigestion, nausea, retching, regurgitation, vomiting, excessive gas, fullness, pain, weight loss II. DIFFERENTIALS FOR THE COMMON GASTROINTESTINAL COMPLAINTS ABDOMINAL PAIN DIARRHEA GI BLEEDING Appendicitis Infection Ulcer disease Gallstone disease Poorly absorbed sugars Esophagitis Pancreatitis Inflammatory Bowel Disease Varices Diverticulitis Microscopic Colitis Vascular lesions Ulcer disease Functional Bowel Disorders Neoplasm Esophagitis Celiac Disease Diverticula GI obstruction Pancreatic Insufficiency Hemorrhoids Inflammatory Bowel Disease Hyperthyroidism Fissures Functional Bowel Disorders Ischemia Inflammatory Bowel Disease Vascular disease Endocrine tumor Infectious Colitis Gynecologic Renal Stone

OBSTRUCTIVE JAUNDICE Bile duct stones Cholangiocarcinoma Cholangitis Sclerosing cholangitis Ampullary stenosis Ampularry carcinoma Pancreatitis Pancreatic tumor

PHYSICAL EXAMINATION IN GASTROENTEROLOGY I. INSPECTION Violaceous Striae Dilated Veins Bulging Flanks Prominent Peristaltic Waves

    

Usually seen in Cushing’s syndrome May be seen in portal hypertension and in inferior vena cava obstruction Associated with ascites May be seen in patients with intestinal obstruction Can also be seen in thin individuals

II. AUSCULTATION (done prior to percussion or palpation as these may alter frequency of bowel sounds) Borborygmi  Prolonged gurgles of hyperperistalsis, aka “stomach growling”  Bruits with audible systolic and diastolic components heard near the midline Bruits almost midway between subxiphoid area and umbilicus may suggest renal artery stenosis  Epigastric bruits heard only during systole may be present in normal individuals


III. PERCUSSION Tympany Dullness Obliterated Trauble’s Space

    

Predominant percussion tone Due to gas in the abdomen Scattered all over the abdomen Signifies presence of underlying mass, organ, fluid and/or feces Percussion of left lower anterior chest wall between lung resonance above and the costal margin Signifies splenomegaly Change in the percussion note from tympany to dullness (over lowest interspace in left anterior axillary line) on inspiration Also signifies splenomegaly

Associated with peritoneal inflammation

 

Dullness shifting to the more dependent side is seen in ascites Easily palpable impulse on the side opposite the pressure (with hands pressed firmly on the midline of the abdomen) suggest ascites Pain in right lower quadrant during left-sided pressure suggests appendicitis Also associated with referred rebound tenderness (right lower quadrant pain on withdrawal of pressure on left side) Abdominal pain on hip flexion and/or extension secondary to irritation of psoas muscle by an inflamed appendix Right hypogastric pain on internal rotation of right hip suggests irritation of obturator muscle by an inflamed appendix May also be seen in appendicitis Sharp increase in right upper quadrant tenderness with a sudden stop in inspiratory effort (while pressure is applied under the costal margin lateral to the border of the rectus muscle) is seen in acute cholecystitis Same procedure may enhance hepatic tenderness (due to multiple causes) but pain is usually less localized

  Splenic Percussion Sign

IV. PALPATION Involuntary rigidity Rebound tenderness Shifting dullness Fluid wave Rovsing’s sign

 

Psoas sign

Obturator sign

Cutaneous Hyperesthesia

 

Murphy’s sign 

V. DIGITAL RECTAL EXAMINATION (DRE) Sphincter Tightness  May be noted in anxiety, inflammation or scaring Sphincter Laxity  May be seen in some neurologic diseases Induration  May be due to inflammation, scarring or malignancy Skin Tags  Soft, pliable tags of redundant skin at anal margin seen in some individuals


GASTROINTESTINAL ENDOSCOPY DIAGNOSTIC  Esophagogastroduodenoscopy (Upper Endoscopy, EGD)

 


 Flexible Sigmoidoscopy

Small Bowel Endoscopy

   

Endoscopic Retrograde Cholangiopancreatography (ERCP)  Endoscopic Ultrasound (EUS)

REMARKS Endoscope inserted through the mouth into the esophagus, stomach, duodenal bulb, and second part of the duodenum Best method of examining the upper gastrointestinal mucosa Scope inserted through anal canal into the rectum and colon Gold standard for diagnosis of colonic mucosal disease Visualizes only the rectum and a portion of the left colon, typically up to 60 cm from the anal verge Capsule endoscopy Push enteroscopy Single- or Double-Balloon Enteroscopy or Spiral Enteroscopy Scope passed through the mouth to the duodenum; the ampulla of Vater is identified and cannulated; and radiographic contrast material is injected into the bile duct and pancreatic duct under fluoroscopic guidance High-frequency ultrasound transducers incorporated into the tip of endoscope Obtains images of the gut wall and adjacent organs, vessels and lymph nodes

        

COMMON INDICATIONS Dyspepsia despite treatment or with signs of alarm UGIB, dysphagia, refractory vomiting Anemia, weight loss, malabsorption Cancer screening LGIB Anemia Diarrhea Obstruction Primarily used for evaluation of diarrhea and rectal outlet bleeding

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Obscure GI bleeding Suspected Crohn’s disease

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Jaundice Cholangitis Gallstone pancreatitis Pancreatic/biliary tumor

Staging of malignancy

APPROACH TO ASCITES I. COMMON CAUSES OF ASCITES CONDITION GROSS APPEARANCE OF ASCITIC FLUID Cirrhosis Straw-colored CHF Straw-colored Neoplasm Straw-colored, hemorrhagic, mucinous or chylous TB Peritonitis Clear, turbid, hemorrhagic, chylous Pyogenic Peritonitis Turbid or purulent Nephrosis Straw-colored or chylous II. PERITONEAL FLUID ANALYSIS LABORATORY FINDING Absolute PMN count > 250/uL Positive gram stain or culture pH < 7.0 RBC count > 50,000 Increased amylase Increased triglycerides Positive malignant cells in cytology

PROTEIN (g/L) 25 >25 >25 1.1 < 1.1

ASSOCIATED CAUSE OF ASCITES Infection (e.g. spontaneous/primary bacterial peritonitis) Hemorrhagic ascites (malignancy, tuberculosis, trauma, ruptured omental varix) Pancreatic ascites, pancreatitis Chylous ascites Malignancy


III. SERUM ASCITES-ALBUMIN GRADIENT (SAAG)  Replaced the description of exudative or transudative ascitic fluid  The gradient correlates directly with portal pressures  SAAG = serum albumin – ascitic fluid albumin SAAG > 1.1 g/dL (or 11 g/L) Portal Hypertension:  Cirrhosis   Cardiac ascites   Budd-Chari Syndrome   Portal Vein Thrombosis   Venoocclusive Disease  Fatty Liver of Pregnancy

SAAG < 1.1 g/dL (or 11 g/L) Peritoneal carcinomatosis Infection (peritonitis, TB) Nephrotic Syndrome Pancreatic or biliary ascites



COMMON CONDITIONS IN GASTROENTEROLOGY PEPTIC ULCER DISEASE (PUD) I. GASTRIC MUCOSAL DEFENSE SYSTEM A. Preepithelial  Mucus-bicarbonate-phospholipid layer to neutralize/buffer gastric acid B. Epithelial  Mucus production  Ionic transporters for maintaining intracellular pH and bicarbonate production  Intracellular tight junctions  Heat shock proteins prevent protein denaturation and protect cells  Restitution: epithelial cells bordering a site of injury migrate to restore a damaged region C. Subepithelial  Microvascular system/bed  Capable of angiogenesis in the event of injury  Provides micronutrients and O2  Removes toxic metabolic by-products II. OVERVIEW OF ULCERS  Usual location Risk of malignancy Usual etiology

 


Character of abdominal pain

Pain in relation to food intake

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Complications  

GASTRIC ULCER (GU) Distal to the junction between antrum and acid secretory mucosa Common (should be biopsied) H. pylori, NSAID-induced injury

DUODENAL ULCER (DU) First portion of the duodenum (within 3 cm of pylorus)

 

Extremely rare H. pylori, NSAID-induced injury  Gastric acid secretion appears to be increased Gastric acid output normal or decreased  HCO3 secretion is significantly decreased  Burning or gnawing discomfort  Pain that awakens the patient Burning or gnawing discomfort from sleep (between midnight and 3 AM) is the most discriminating symptom  Occurs 90 minutes to 3 hours after a meal Precipitated by food  Relieved by antacids or food Bleeding: melena or coffee-ground emesis Penetrating ulcer: pain becomes constant, no longer relieved by antacids, radiates to the back Perforation: sudden severe, generalized abdominal pain Gastric output obstruction: pain worsening with meals, vomiting of undigested food

III. HELICOBACTER PYLORI AND NSAIDS A. Helicobacter pylori  S-shaped gram-negative microaerophilic rod with multiple sheathed flagella which can transform into coccoid form (dormant state)  Bacterial urease aids in infection by producing ammonia from urea, which then alkalinizes surrounding pH


RISK FACTORS FOR HIGHER COLONIZATION RATES  Poor socioeconomic status  Low educational attainment  Crowded and unsanitary conditions


PUD Gastric mucosa-associated lymphoid tissue (MALT) lymphoma Gastric adenocarcinoma

B. NSAID-induced Disease  Interruption of prostaglandin synthesis can impair mucosal defense and repair leading to mucosal injury  Established risk factors o Advanced age o History of ulcer o Concomitant glucocorticoid/anticoagulant/clopigodrel use o High-dose/multiple NSAIDs o Serious/multisystem disease IV. FORREST CLASSIFICATION OF ULCERS  Classification of Upper GI Bleed (UGIB) used for selecting patients for endoscopic treatment CLASSIFICATION DESCRIPTION Acute Hemorrhage Type IA 100%  Arterial spurting Type IB 50%  Arterial oozing Signs of recent hemorrhage Type IIA 43%  Visible vessel Type IIB 22%  Adherent clot Type IIC 10%  Pigmented flat spot Lesions without active bleeding Type III 5%  No stigmata of recent bleed; or fibrin-coated clean ulcer base



Barium studies of proximal GIT

Endoscopy (EGD)

Tests for detection of H. pylori

Commonly used as a first test for documenting an ulcer o DU: appears as a well-demarcated crater, most often seen in the bulb o GU: discrete crater with radiating mucosal folds originating from the ulcer margin  Allows direct visualization of the mucosa  Most sensitive and specific approach for examining the upper GIT  Facilitates documentation of a mucosal defect and tissue biopsy to rule out malignancy (GU) or H. pylori Invasive tests (Endoscopy/Biopsy required)  Rapid Urease (prone to false negatives with recent therapy)  Histology  Culture Non-Invasive Tests  Urea Breath Test (test of choice for documenting eradication)  Serology  Stool antigen


VI. MANAGEMENT OF PUD  Relief of symptoms  Promote ulcer healing  Prevent ulcer recurrence and complications A. Acid Neutralizing/Inhibitory Drugs CLASS EXAMPLES Aluminum hydroxide Antacids

Magnesium hydroxide

H2 Receptor Antagonists

Cimetidine Ranitidine Famotidine


Neutralizes intragastric acidity

Competitive inhibition at the parietal cell H2receptor, suppresses acid secretion Covalently bind and irreversibly inhibit H+, K+-ATPase Most potent acid inhibitory agent Maximum efficacy if taken before a meal

 Proton Pump Inhibitors (PPIs)

Omeprazole Esomeprazole Lansoprazole Rabeprazole Pantoprazole

B. Cytoprotective Agents CLASS




BismuthContaining Preparations

Bismuth subsalicylate (BSS, Pepto-Bismol)

Prostaglandin Analogues


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MECHANISM OF ACTION  Becomes a viscous paste within the stomach and duodenum, binding primarily to sites of active ulceration  Act as a physiochemical barrier 

Mechanism is unclear

Enhancement of mucosal defense and repair

     

SIDE EFFECTS Constipation Diarrhea Avoid in patients with CKD Headache, fatigue, myalgias Relatively safe Headache, abdominal pain, diarrhea, flatulence, dermatitis, pruritus, dry mouth, blurred vision, angioedema



   

Black stools Constipation Darkening of the tongue Neurotoxicity (longterm) Diarrhea Contraindicate in pregnancy (Misoprostol)

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C. Helicobacter pylori Eradication  Antibiotic resistant strains are the most common cause for treatment failure in compliant patients  Dual therapy and shorter regimens (7-10 days) are not as effective and are not recommended 1. Triple Therapy for 14 days DRUG  Omeprazole Any Proton Pump Inhibitor (PPI),  Lansoprazole plus  Esomeprazole  Pantoprazole  Rabeprazole Either of the following, plus  Clarithromycin (first line)  Metronidazole 2. Non-Bismuth Quadruple (Sequential) Therapy for 14 days  PPI plus Amoxicillin for 5-7 days, followed by  PPI plus Clarithromycin and Metronidazole for 5-7 days

DOSE 20 mg BID 30 mg BID 40 mg OD 40 mg OD 20 mg BID 500 mg BID 500 mg BID


VII. PUD-RELATED COMPLICATIONS Gastrointestinal Bleeding

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Gastric Outlet Obstruction

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Most common complication of PUD Second most common ulcer-related complication Penetration: form of perforation in which ulcer bed tunnels into adjacent organ o DU: tends to penetrate posteriorly into the pancreas, leading to pancreatitis o GU: tends to penetrate into the left hepatic lobe Least common ulcer-related complication Relative obstruction secondary to ulcer-related inflammation and edema in the prepyloric region

GASTROINTESTINAL BLEEDING I. COMMON CAUSES OF UPPER GASTROINTESTINAL BLEEDING (UGIB)  Most common upper GI causes: ulcer disease, gastroduodenitis, and esophagitis  Usually presents with hematemesis or melena (massive UGIB can also present with hematochezia) A. Bleeding Peptic Ulcer Disease (BPUD)  Most common cause of UGIB  Usually secondary to NSAID use or H. pylori infection  Ulcer: a break in the mucosal surface >5mm ECG FINDINGS RISK OF REBLEEDING Clean-based ulcer -/+ Flat pigmented spots Adherent clots covering ulcer base Platelet plug protruding from a vessel wall in the base of an ulcer (sentinel clot) Active spurting from an ulcer

+ ++ +++

MANAGEMENT No IV PPI or endoscopic treatment IV PPI +/- endoscopic treatment IV PPI + endoscopic treatment


DISPOSITION Discharge Ward for 3 days

ICU for a day then ward for 2 more days

B. Bleeding Esophageal Varices (BEV)  Second most common cause of UGIB  Usually arises due to portal hypertension from liver cirrhosis  Poorer outcomes compared to patients with other sources of UGIB C. Hemorrhagic and Erosive Gastropathy (“Gastritis”)  Endoscopically visualized subepithelial hemorrhages and erosions  Usually seen with NSAIDs, alcohol intake and stress (serious trauma, major surgery, extensive burns, major intracranial disease, or severe medical illness) D. Mallory-Weiss Tear  A linear mucosal rent near or across the gastroesophageal junction that is often associated with retching, vomiting or incessant coughing E. Dieulafoy’s Lesion  Large-caliber arteriole that runs immediately beneath GI mucosa and bleeds via a pinpoint mucosal erosion  Seen most commonly on the lesser curvature of the proximal stomach II. COMMON CAUSES OF LOWER GASTROINTESTINAL BLEEDING (LGIB)  Most common lower GI causes: hemorrhoids, anal fissures, diverticula, neoplasms (adenocarcinoma), ischemic colitis, and arteriovenous malformations  Usually presents with hematochezia


A. Hemorrhoidal Disease  Patients commonly present for two reasons: bleeding and protruding rectal mass  Severe pain may indicate a thrombosed hemorrhoid STAGE CHARACTERISTICS TREATMENT  Fiber supplementation I Enlargement with bleeding  Cortisone suppository  Sclerotherapy Protrusion with spontaneous reduction  Fiber supplementation II  Cortisone suppository  Fiber supplementation Protrusion requiring manual reduction  Cortisone suppository III  Banding  Operative hemorrhoidectomy  Fiber supplementation IV Irreducible protrusion  Cortisone suppository  Operative hemorrhoidectomy B. Diverticular Disease  Hemorrhage from a colonic diverticulum: most common cause of hematochezia in patients >60 years old  Bleeding more often seen from the right colon, usually abrupt and painless  Minor/occult bleeding is not characteristic  Localization of diverticular bleeding should include colonoscopy, which may be diagnostic and therapeutic C. Anal Fissure  Most common cause of rectal bleeding in infancy  Acquired from trauma to the anal canal following defecation  More common in the posterior anal canal  Relative ischemia in the region of the fissure leads to poor healing III. MANAGEMENT OF BLEEDING A. Initial Resuscitation 1. Airway Protection (intubation to prevent aspiration)  Decreased sensorium (shock, hepatic encephalopathy)  Massive hematemesis  Active variceal bleeding 2. Restoration of Intravascular Volume  IV fluids: isotonic state; lactated Ringer’s solution  Transfusion with packed RBCs (or whole blood if necessary) 3. Correction of Coagulopathy (if present)  Discontinuation of offending anti-coagulants followed by infusion of FFP  Parenteral vitamin K for prolonged PT (INR) from warfarin, liver disease  Platelet infusion if with significant thrombocytopenia


B. Therapy for Specific Lesions DISEASE

TREATMENT High-dose PPIs: Omeprazole 80 mg IV bolus followed by 8 mg/hour infusion for 72 hours (See also chapter 1)  Therapeutic endoscopy (advantage of immediate treatment)  Surgery for intractable or recurrent bleeding  H. pylori eradication if with evidence of infection (14-day antibiotic regimens)  Avoidance of NSAIDs if possible 1. Vasoactive Agents  Reduce portal venous pressures acutely by splanchnic vasoconstriction  Somatostatin 275 mcg IV bolus followed by 3 mg infusion over 12 hours  Octreotide 50 mcg/hour infusion 

Peptic Ulcer Disease (PUD)

2. Non-selective Beta-Blockers  Decrease rates of recurrent bleeding  β-blockade allows unopposed alpha-receptor mediated vasoconstriction of splanchnic vessels  propranolol 10 mg PO TID (starting dose)

Variceal Hemorrhage

3. Antibiotics for Patients with Cirrhosis to Decrease Infections (7-day course)  Ceftriaxone 1 g IV OD  Ciprofloxacin 400 mg IV q12  Levofloxacin 500 mg IV OD  Norfloxacin 400 mg PO BID 4. Endoscopic / Surgical Options  Ligation or banding: endoscopic therapy of choice as it controls active hemorrhage (lower rates of success for gastric compared to esophageal varices)  Sclerotherapy  Cyanoacrylate “glue” injection  Balloon tamponade with a Sengstaken-Blakemore tube or Minnesota tube  Transjugular Intrahepatic Portosystemic Shunt (TIPS)  Liver transplantation

Stress Ulcer Colonic Diverticulum


Anal Fissures

5. Judicious Blood Transfusion (overtransfusion may further increase portal pressures)  Prophylactic therapy: PPIs, Histamine-Receptor Antagonists and Sucralfate  Mesenteric angiography with coiling  Segmental resection of the colon  Sitz baths, high-fiber diet, stool softeners  Banding  Sclerotherapy  Hemorrhoidectomy (excisional vs stapled)  Sitz baths, high-fiber diet, stool softeners, topical anesthetics  For chronic fissures (>6 weeks): nifedipine or NTG ointment applied TID, botulinum toxin type A injections  Surgery: anal dilatation and lateral internal sphincterotomy


OVERVIEW OF LIVER DISEASE I. BASIC PATTERNS OF LIVER DISEASE  Hepatocellular (viral, alcoholic liver disease): features of liver injury, inflammation & necrosis predominate  Cholestatic (obstructive diseases): features of inhibition of bile flow predominate  Mixed (drug-induced liver diseases): features of both II. MAJOR RISK FACTORS FOR LIVER DISEASE  Alcohol use, personal habits, sexual activity, travel, occupation, injection drug use  Medications (including herbal compounds, birth control pills, and over-the-counter medications)  Exposure to jaundiced or other high-risk persons  Recent surgery  Remote or recent transfusion with blood and blood products  Accidental exposure to blood or needle-stick  Familial history of liver disease III. CLINICAL MANIFESTATIONS Constitutional Symptoms Liver-specific Symptoms

Icterus Palmar erythema Spider angioma

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Hepatomegaly Splenomegaly Ascites Peripheral edema

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Hepatic encephalopathy

Fetor hepaticus

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Umbilical hernia Caput medusa

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Wilson’s disease

Alcoholic liver disease Hemochromatosis

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SYMPTOMS OF HEPATIC DISEASE Fatigue, poor appetite, weakness, nausea and malaise Fatigue: most common and most characteristic symptom of liver disease Dark urine, light stools, itching, abdominal pain and bloating Jaundice: hallmark of liver disease and the most reliable marker of severity SIGNS OF HEPATIC DISEASE Check sclerae, skin, mucous membrane below the tongue Occurs in acute and chronic liver disease; prominent in persons with cirrhosis Superficial tortuous arterioles seen on the arms, face, upper torso; fill outwards from the center (unlike telangiectasis) See in venoocclusive disease, infiltrative disorders, hepatic malignancy, alcoholic hepatitis Hepatic tenderness: the most reliable physical finding in examining the liver Subtle significant finding in liver disease Best appreciated by percussing for shifting dullness Contributing factors: hypoalbuminemia, venous insufficiency, heart failure, and medications First signs: change in sleep patterns, change in personality, irritability, mental dullness Confusion, disorientation, stupor and eventually coma supervene Acute liver failure: excitability, mania Slightly sweet, ammonia-like odor in patients, especially if there is portovenous shunting of blood Secondary to increased intraabdominal pressures from ascites Results from recannulation of umbilical vein: collateral veins radiating from umbilicus For males: gynecomastia, testicular atrophy, loss of male-pattern hair distribution DISEASE-ASSOCIATED FINDINGS Kayser-Fleischer rings (golden-brown copper pigment deposited in periphery of cornea) Dupuytren contracture and parotid enlargement Slate-gray pigmentation of skin


IV. DIAGNOSTICS TESTS BASED ON DETOXIFICATION & EXCRETORY FUNCTIONS  Unconjugated (indirect) bilirubin: seen in hemolytic disorders, Crigler-Najjar and Gilbert’s syndrome Serum Bilirubin  Conjugated (direct) bilirubin: almost always implies liver or biliary tract disease  Higher levels indicate more severe hepatocellular damage/injury in viral hepatitis and drug-induced liver disease  Enzymes that reflect damage to hepatocytes  ALT is more specific as an indicator of liver injury than AST  Elevations of >1000 U/L occur almost exclusively in: o Viral hepatitis o Ischemic liver injury (prolonged hypotension or acute heart failure) Aminotransferases o Toxin- or drug-induced liver injury o Acute phase of biliary obstruction caused by passage of gallstone into CBD  Patterns of liver injury: o AST:ALT2 in alcoholic liver disease o Alkaline phosphatase > aminotransferases in cholestatic conditions Alkaline Phosphatase (ALP)  Enzymes that reflect cholestasis 5’Nucleotidase  Elevations of ALP greater than 4 times seen in cholestatic liver disease, y-glutamyl Transpeptidase infiltrative liver diseases, rapid bone turnover (GGT)  Elevations in both GGT and alkaline phosphatase indicative of biliary disease

Serum Albumin

Serum Globulins

Clotting Factors

Ultrasound, CT, MRI MRCP, ERCP Doppler US and MRI

TESTS THAT MEASURE BIOSYNTHETIC FUNCTION OF LIVER  Synthesized exclusively by the hepatocytes  Half-life of 18-20 days, therefore not a good indicator of acute or mild dysfunction  Hypoalbuminema is more common in chronic liver disorders such as cirrhosis, reflecting severe liver damage and decreased albumin synthesis  y-globulins are increased in CLD due to increased antibody synthesis to fight off intestinal bacteria that the cirrhotic liver failed to clear from the hepatic circulation  Single best acute measure of hepatic synthetic function  All clotting factors are synthesized in the liver except for factor VIII (produced by endothelial cells)  Prothrombin time measures factors II, V, VII, X  Vitamin K-dependent factors: II, VII, IIX, X  Marked prolongation of PT >5 sec above control not corrected by IV Vitamin K is a poor prognostic sign       

Liver Biopsy  

IMAGING AND OTHER TESTS Most commonly employed for imaging of the liver Ultrasound is first-line if initial blood tests suggest cholestasis (to check for dilated ducts/gallstones) Procedures of choice for visualization of the biliary tree Hepatic vasculature and hemodynamics Doppler US is first test ordered if suspecting Budd-Chari syndrome The criterion standard in the evaluation of patients with liver disease Subject to sampling error in focal infiltrative disorders such as hepatic metastasis Should not be the initial procedure in the diagnosis of cholestasis Contraindications to percutaneous approach: significant ascites and prolonged INR (may use transjugular approach instead)


V. DISEASE-SPECIFIC LABORATORY TESTS DISEASE DIAGNOSTIC TESTS AND EXPECTED FINDINGS Autoimmune Hepatitis  Antinuclear antibody (ANA) or anti-smooth muscle antibody (SMA)  Elevated IgG levels Primary Biliary Cirrhosis  AMA (anti-mitochondrial antibody); elevated IgM levels Primary Sclerosing  p-ANCA; cholangiography Cholangitis Wilson’s Disease  Decreased serum ceruloplasmin and increased urinary copper  Increased hepatic copper level Hemochromatosis  Elevated iron saturation and serum ferritin  Genetic testing for HFE gene mutations Hepatocellular Cancer  Elevated alpha-fetoprotein level >500; US or CT image of mass VI. OVERVIEW OF SEROLOGY FOR VIRAL HEPATITIS HEPATITIS A (HAV) Anti-HAV (IgM)  Diagnosis of hepatitis A during acute illness and persists for several months (Antibody to HAV)  Detected when aminotransferase activity is elevated & fecal HAV shedding still occurring Anti-HAV (IgG)  After acute illness, anti-HAV of the IgG class remains detectable indefinitely (Antibody to HAV)  Predominates during convalescence  Marker of immunity to reinfection HBsAg (Hepatitis B Surface Agent)

  

Anti-HBs   Anti-HBc (IgM or IgG)

HBeAg (Hepatitis B ‘e’ Antigen)

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HEPATITIS B (HBV) First virologic marker detectable in serum within 1-12 weeks after infection with HBV Chronic HBV infection: HBsAg remains detectable beyond six months After HBsAg disappears, anti-HBsAg becomes detectable and remains detectable indefinitely thereafter (protective antibody) Also seen after immunization with hepatitis B vaccine (anti-HBs would be the only serologic marker to appear) IgM anti-HBc: predominates during the first six months after acute infection, including anti-HBc window period IgG anti-HBc: predominant class of anti-HBc beyond six months An isolated reactive anti-HBc can be seen in the gap or window period Appears concurrently with or shortly after HBsAg Qualitative marker on HBV replication and relative infectivity HBsAg-positive serum containing HBsAg is more likely to be highly infectious Its disappearance may be a harbinger of clinical improvement and resolution of infection Persistence beyond the first 3 months of acute infection is predictive of development of chronic infection Its appearance coincides with a period of relatively lower infectivity More sensitive and quantitative indicator of HBV replication


 


 

HEPATITIS C (HCV) Diagnosis of Hepatitis C Most sensitive test for HCV infection: “gold standard” in establishing a diagnosis of HCV


HEPATITIS D (HDV) Testing for anti-HDV is useful in those with hepatitis B and severe/fulminant disease

Anti-HEV (IgM/IgG)

HEPATITIS E (HEV) Not routinely available


VII. SUMMARY OF TESTS FOR VIRAL HEPATITIS DISEASE DIAGNOSTIC TESTS AND EXPECTED FINDINGS Hepatitis A  Anti-HAV IgM Hepatitis B Acute infection  HBsAg, IgM anti-HBc Chronic infection  HBsAg, IgG anti-HBc Markers of replication  HBeAg, HBV DNA Hepatitis C  Anti-HCV and HCV RNA Hepatitis D (Delta)  HBsAg and anti-HDV HBV/HDV coinfection  IgM anti-HBc and anti-HDV HDV superinfection  IgG anti-HBc and anti-HDV Hepatitis E  Anti-HEV

VIRAL HEPATITIS I. ACUTE VIRAL HEPATITIS A. Overview of Clinical Profile FEATURE HAV Onset Acute Predominant Mode/s of Transmission Severity Progression to Chronicity Prognosis Prophylaxis

HCV Insidious


Percutaneous, perinatal, sexual



Occasionally severe



Occasional (common if perinatal) Variable HBIG Recombinant vaccine

Excellent IG Inactivated Vaccine


Additional Notes

HBV Insidious or acute


More symptomatic/ severe infection in adults compared to children

Interferon, Lamivudine, Adefovir, PEG-IFN, Entecavir, Telbivudine, Tenofovir

The only hepatitis virus with a DNA genome (other types have an RNA genome)

HDV Insidious or acute Percutaneous, sexual

HEV Acute



Occasionally severe Common






HBV vaccine




Defective virus that requires helper function of HBV for replication and expression

Usually from contaminated water supply after monsoon flooding in endemic areas

PEG-IFN + Ribavirin Telaprevir, Boceprevir Chronic liver disease from chronic hepatitis C is the most frequent indication for liver transplant


B. Clinical Manifestations Prodromal Symptoms


 

Recovery Phase

SYMPTOMS AND SIGNS Anorexia, nausea and vomiting, fatigue, malaise, arthralgias, myalgias, headache, photophobia, pharyngitis, cough & coryza may precede the onset of jaundice by 1-2 weeks With the onset of jaundice, the constitutional prodromal symptoms usually diminish Complete clinical and biochemical recovery occurs: o 1-2 months after hepatitis A and E o 3-4 months after the onset of jaundice in hepatitis B and C (among healthy adults, acute hepatitis B is self-limited in 95-99% while hepatitis C is selflimited in only 15%)



Bilirubin Prothrombin Time Alkaline Phosphatase Hypoalbuminemia

   

LABORATORY FEATURES Increase during the prodromal phase of acute viral hepatitis and precede the rise in bilirubin level Peak levels vary from 400-4000 IU or more When jaundice appears, bilirubin typically rises Prolonged values reflect a severe hepatic synthetic defect Normal or mildly elevated

Uncommon in uncomplicated acute viral hepatitis

C. Diagnosis of Acute Hepatitis DIAGNOSTIC INTERPRETATION Acute hepatitis B Acute hepatitis A superimposed on chronic hepatitis B Acute hepatitis A and B Acute hepatitis A Acute hepatitis A and B (HBsAg below detection threshold) Acute hepatitis B (HBsAg below detection threshold) Acute hepatitis C

HBsAg + +

IgM Anti-HAV +

IgM Anti-HBc + -

Anti-HCV -

+ -

+ + +

+ +










D. Sequelae of Acute Viral Hepatitis 1. Fulminant Hepatitis  Most feared complication of viral hepatitis (massive hepatic necrosis)  Primarily seen in hepatitis B, E and D (mnemonic: B-E-D-ridden for fulminant hepatitis)  Signs and symptoms of encephalopathy that may evolve to deep coma  Terminal events: brainstem compression, GI bleeding, sepsis, respiratory failure, cardiovascular collapse, renal failure  Management: restriction of protein intake, oral lactulose or neomycin, supportive (fluids, circulation, respiration, correction of bleeding and hypoglycemia), liver transplantation may be life-saving 2. Chronic Liver Disease (CLD) Hepatitis A or E Neither HAV nor HEV causes chronic liver disease Hepatitis B Chronic: persistence of HBeAg for >3 months or HBsAg for >6 months after acute hepatitis Hepatitis C After acute HCV infection, the likelihood of remaining chronically infected approaches 90% II. CHRONIC VIRAL HEPATITIS A. Interpretation of Hepatitis B Serologic Markers INTERPRETATION Acute hepatitis B, high infectivity Chronic hepatitis B, high infectivity Chronic hepatitis B, low infectivity Anti-HBc “window” Hepatitis B in remote past Recovery from hepatitis B Immunization with HBsAg (after vaccination)

HBsAg + + + -

Anti-HBs + +

Anti-HBc IgM IgG IgG IgM IgG IgG -

HBeAg + + +/-

Anti-HBe + +/+/+/-

B. Sequelae  Liver cirrhosis (see separate section on Liver Cirrhosis for more information)  Hepatocellular carcinoma (hepatitis B and C), especially for individuals who acquired hepatitis B perinatally


C. Management FACTORS THAT AFFECT DECISION TO TREAT AND/OR DURATION OF TREATMENT HEPATITIS B HEPATITIS C  Clinical status (presence of cirrhosis, compensated vs. decompensated)  Detectable HCV RNA in serum  Family history of hepatocellular carcinoma  HCV genotype  HBsAg status  HBV DNA titers  ALT levels TREATMENT  Pegylated interferon (PEG IFN) once weekly  Pegylated interferon (PEG IFN) + Ribavirin SC injection o Genotype 1: 48 weeks o Genotype 2: 24 weeks  Lamivudine 100 mg PO OD (first successful o Most pronounced side effect of ribavirin is oral antiviral agent) hemolysis  Entecavir 0.5 mg PO OD (most potent of the antivirals)  Tenofovir 300 mg PO OD

ALCOHOLIC LIVER DISEASE I. ETIOPATHOGENESIS  Threshold for developing alcoholic liver disease o Men: >60-80 g/day of alcohol for 10 years o Women: >20-40 g/day of alcohol for 10 years o >160 g/day has a 25x increased risk of alcoholic cirrhosis  The following all contain ~12 g of alcohol: o One bottle of beer o Four ounces of wine o One ounce of 80% spirits II. CLINICAL MANIFESTATIONS PATHOLOGY SYMPTOMS AND SIGNS Fatty liver  RUQ pain, nausea, fatigue  Alcoholic hepatitis

   Alcoholic cirrhosis

 

 

Fever, spider nevi, jaundice and abdominal pain Portal hypertension, ascites, or variceal bleeding can occur in the absence of cirrhosis

RUQ pain, fever, nausea and vomiting, diarrhea, anorexia and malaise More specific complications: ascites, edema or upper GI hemorrhage Jaundice, encephalopathy, hepatomegaly, splenomegaly Liver edge may be firm and nodular Scleral icterus, palmar erythema, spider angiomas, parotid gland enlargement, digital clubbing, muscle wasting, edema and ascites Males: decreased body hair, testicular atrophy, gynecomastia Females: menstrual abnormalities

SOME LABORATORY FINDINGS AST or ALT increased 2 to 7-fold AST/ALT ratio >1 Bilirubin may be markedly increased in alcoholic hepatitis despite only modest elevation in alkaline phosphatase  PMN >5500/uL predicts severe alcoholic hepatitis when discriminant function >32   

     

Hypoalbuminemia Prolonged PT Increased bilirubin Anemia Thrombocytopenia (due to portal HPN and hypersplenism) CT/UTZ: nodular liver, splenomegaly, venous collaterals


III. MANAGEMENT  Complete abstinence from alcohol is the cornerstone in the treatment of alcoholic liver disease  Glucocorticoids may be used for severe alcoholic hepatitis (discriminant function >32 or MELD >20) Discriminant function = 4.6 x [PT prolongation above control in seconds] +serum bilirubin

mg dL

o Steroid dosing: prednisone 40 mg/day or prednisolone 32 mg/day for 4 weeks, then tapered over 4 weeks o Exclusion criteria: active GI bleeding, renal failure, pancreatitis TNF inhibitor pentoxifylline (400 mg PO TID x 4 weeks) has demonstrated improved survival in severe cases


Chronic liver disease  compensated cirrhosis  decompensated cirrhosis  death The presence of complications differentiates decompensated from compensated cirrhosis: o Variceal hemorrhage o Ascites o Hepatic encephalopathy o Jaundice

II. CAUSES OF CIRRHOSIS  Alcoholic cirrhosis  Chronic viral hepatitis B or C  Autoimmune hepatitis  Nonalcoholic steatohepatitis  Biliary cirrhosis  Cardiac cirrhosis  Inherited metabolic liver disease (e.g., hematochromatosis, Wilson’s Disease) III. COMPLICATIONS OF CIRRHOSIS  Spontaneous bacterial peritonitis  Hepatic encephalopathy  Portal hypertension  Portopulmonary hypertension  Hepatorenal syndrome  Hepatopulmonary syndrome  Others: malnutrition, bone disease, coagulopathy, hematologic (thrombocytopenia, neutropenia) A. Spontaneous Bacterial Peritonitis (SBP)  Spontaneous infection of the ascitic fluid without an intra-abdominal source  Usually occurs in the setting of liver cirrhosis 

Clinical features of Spontaneous Bacterial Peritonitis o Presents as fever, altered mental status, elevated WBC, and abdominal pain/discomfort o Most common organisms are Escherichia coli and other gut bacteria o Isolation/growth of more than 2 organisms should raise suspicion for perforated viscus (secondary bacterial peritonitis) o Diagnosis: fluid sample has an absolute neutrophil count >250/uL

Treatment: Cephalosporins or Quinolones o Cefotaxime 2 g IV q8 x 5 days o Ofloxacin 400 mg PO BID x 8 days o Ciprofloxacin 200 mg IV q12 x 2 days followed by ciprofloxacin 500 mg PO q 12 x 5 days o Ceftriaxone 1 g IV q8 x 5 days


B. Hepatic Encephalopathy  Alteration in mental status and cognitive function occurring in the presence of liver failure  In acute liver injury, development of encephalopathy is a requirement for diagnosis of fulminant hepatic failure  Encephalopathy is more commonly seen in chronic liver disease  Symptoms are due to neurotoxins that are not removed by the liver because of vascular shunting 

Clinical features of Hepatic Encephalopathy o Symptoms: confused, changes in behavior, violent, difficult to manage, sleepy and difficult to rouse o Asterixis or liver flap: sudden forward movement of the wrist after it is bent back on an extended arm (cannot be elicited if already comatose) o Cerebral herniation is a feared companion of brain edema o Correlation between severity of liver disease and serum ammonia levels is often poor GRADE LEVEL OF PERSONALITY AND INTELLECT NEUROLOGIC CONSCIOUSNESS ABNORMALITIES Normal Normal Normal 0 Inverted sleep pattern, Forgetful, mild confusion, agitation, Tremor, apraxia, 1 restless irritable incoordination, impaired handwriting Disorientation to time, amnesia, Asterixis, dysarthria, Lethargic, slow responses decreased inhibitions, inappropriate hypoactive reflexes 2 behavior Somnolent but can be Asterixis, hyperactive aroused, confused Disorientation to place, aggressive reflexes, Babinski’s 3 sign, muscle rigidity Coma Nil Decerebrate 4

Precipitating Events in Hepatic Encephalopathy o Hypokalemia: hypokalemia causes increased ammoniagenesis (alkaline tide) o Infection o Increased dietary protein load o Electrolyte disturbances o GI bleeding

Treatment of Hepatic Encephalopathy Nutrition  Protein restriction is discouraged as it has negative impact on overall nutrition  Replace animal-based protein with vegetable-based protein in the diet  Mainstay of treatment for encephalopathy  Initial dose: 30-40 mL orally, once or twice daily (dose may be increased as tolerated) Lactulose  Goal is to promote 2-3 soft stools per day  Mechanisms of action: o Colonic acidification o Catharsis  Adjunctive to lactulose  Poorly absorbed antibiotics: Antibiotics o Neomycin 250 mg BID-QID o Metronidazole 250-500 mg TID (given alternately to reduce individual side effects)  Rifamixin 550 mg BID has been very effective as well, with a better safety profile Supportive  Management/correction of the above-mentioned precipitating factors  Zinc supplementation may be helpful

C. Portal Hypertension (HPN)  Elevation of hepatic venous pressure gradient >5 mmHg  Development of portal hypertension is usually revealed by the presence of thrombocytopenia, splenomegaly and development of ascites, encephalopathy and/or esophageal varices with or without bleeding


Classification of Portal Hypertension PRE-HEPATIC HEPATIC Most common: can be presinusoidal, Affects the portal venous system before it enters the liver sinusoidal, postsinusoidal Presinusoidal  Schistosomiasis Portal vein thrombosis  Congenital hepatic fibrosis Splenic vein thrombosis Sinusoidal Massive splenomegaly (Banti’s  Cirrhosis syndrome)  Alcoholic hepatitis Postsinusoidal  Hepatic sinusoidal obstruction (venoocclusive syndrome) 

POST-HEPATIC Affects the hepatic veins and venous damage to the heart Budd-Chiari syndrome Inferior vena caval webs Cardiac causes  Restrictive cardiomyopathy  Constrictive pericarditis  Severe CHF

Complications of Portal Hypertension GASTROESOPHAGEAL VARICES  Resistance to portal flow leads to increased resistance in portal pressure Mechanism  Decreased splanchnic arteriolar resistance leads to increased splanchnic flow (increased portal blood flow) Treatment See table in separate section on Management on GI bleeding ASCITES Due to portal HPN, there will be vasodilation of the splanchnic arterial system, resulting in:  Increased splanchnic pressure due to increased portal venous flow  ascites Mechanism  Underfilling of arterial system  RAAS activation  hyperaldosternism  Na+/H2O retention  ascites  Decreased synthetic function of the liver  hypoalbuminemia  decreased oncotic pressure  ascites  Small amount of ascites: dietary sodium restriction (51 >3.0 < 30 < 3.0 >6 > 2.3 Poorly controlled Advanced

Interpretation: o Class A = scores 5-6


o o 

Class B = score of 7-9 Class C = scores of 10-15

Decompensation indicates cirrhosis with a score of > 7 (this level has been the accepted criterion for listing a patient for liver transplantation)

B. Model for End-Stage Liver Disease MELD) Score  Scoring system to predict prognosis of patients with liver disease and portal hypertension  This score is now used for prioritizing allocation for liver transplantation  Calculated using three non-invasive variables: o PT-INR o Serum bilirubin o Serum creatinine

ACUTE PANCREATITIS I. ETIOPATHOGENESIS  Inflammation of the pancreas due to activation of pancreatic enzymes within the pancreas  The pathologic spectrum of acute pancreatitis o Interstitial pancreatitis: mild and self-limited disorder o Necrotizing pancreatitis: more severe form  Common etiologies (G-A-T-E-D): o Gallstones: most common cause o Alcohol: 2nd most common cause o HyperTriglycerides (usually with serum triglycerides >1000 mg/dL) o Endoscopic retrograde cholangiopancratography (ERCP) o Drugs o Trauma o Postoperative o Sphincter of Oddi dysfunction  For recurrent attacks of pancreatitis, the two most common etiologies: alcohol and cholelithiasis  Autodigestion: currently accepted pathogenic theory  Proteolytic enzymes (e.g., trypsinogen, chymotrypsinogen, proelastase) are activated in the pancreas rather than in the intestinal lumen II. CLINICAL MANIFESTATIONS OF PANCREATITIS A. Symptoms and Signs of Acute Pancreatitis

Abdominal pain

Other symptoms General PE

         

Shock  Abdominal Tenderness Bowel Sounds Jaundice (infrequent)

  

SYMPTOMS Major symptom of acute pancreatitis Quality: steady and boring in character Location: epigastrium and peiumbilical region Radiation: back, chest, flanks, lower abdomen More intense when supine Relieved upon sitting with the trunk flexed and knees drawn up Nausea, vomiting, and abdominal distention SIGNS Distressed and anxious patient Low-grade fever, tachycardia, and hypotension are fairly common Hypovolemia secondary to exudation of blood and plasma proteins into the retroperitoneum Systemic effects of proteolytic and lipolytic enzymes released into the circulation Compared with the intense pain, this sign may be unimpressive Decreased or absent Due to edema of the pancreatic head with compression of the


Pulmonary findings Cullen’s Sign Turner’s Sign

  

intrapancreatic portion of the common bile duct (CBD) Basilar rates, atelectasis, pleural effusion (most frequently left sided) Blue discoloration around the umbilicus (results from hemoperitoneum) Blue-red-purple or green-brown discoloration of the flanks (reflects tissue catabolism of hemoglobin)

B. Revised Atlanta Definitions of Morphologic Features of Acute Pancreatitis MORPHOLOGIC FEATURE DEFINITION Interstitial Pancreatitis  Acute inflammation of pancreatic parenchyma & peripancreatic tissues  No recognizable tissue necrosis Necrotizing Pancreatitis  Inflammation associated with parenchymal and/or peripancreatic necrosis  Peripancreatic fluid associated with interstitial edematous pancreatitis Acute Pancreatic Fluid  No associated necrosis Collection  Applies only to areas of fluid seen within the first 4 weeks after onset of interstitial edematous pancreatitis and without features of a pseudocyst  Encapsulated collection of fluid with a well-defined inflammatory wall Pancreatic pseudocyst usually outside the pancreas with minimal or no necrosis  Occurs > 4 weeks after onset of interstitial edematous pancreatitis Acute necrotic collection  Collection containing variable amounts of both fluid and necrosis (ANC) associated with necrotizing pancreatitis  Mature, encapsulated collection of pancreatic and/or peripancreatic Walled-off Necrosis (WON) necrosis that has developed a well-defined inflammatory wall  Usually occurs > 4 weeks after onset of necrotizing pancreatitis C. Revised Atlanta Classification: Clinical Course, Definitions and Classifications 1. Phases of Acute Pancreatitis  Early (2 weeks)

 

Severity is defined by clinical parameters, rather than morphologic findings Most exhibit SIRS and are predisposed to organ failure Three organ systems should be assessed to define organ failure: respiratory, cardiovascular, and renal Persistent organ failure (>48 hours): most important clinical finding with regard to severity of the acute pancreatitis episode Characterized by a protracted course of illness and may require imaging to evaluate for local complications Important clinical parameter of severity: persistent organ failure May require supportive measures (dialysis, ventilator support, TPN)

2. Severity of Acute Pancreatitis   Mild  Moderately Severe


 

Without local complications or organ failure Self-limited disease and subsides within 3-7 days after treatment is instituted Oral intake may be resumed if patient is hungry, has normal bowel function and has no nausea/vomiting Characterized by transient organ failure (resolves in 48 hours) CT scan or MRI should be obtained to assess for necrosis and/or complications

3. Imaging in Acute Pancreatitis  Two types of pancreatitis are recognized on imaging: interstitial or necrotizing  CT imaging: best evaluated 3-5 days into hospitalization when patients are not responding to supportive care to look for local complications such as necrosis III. DIAGNOSTICS



Lipase Complete blood count Renal function

         

Serum chemistry


      

Abdominal CT Scan Sonography

 

Acute pancreatitis: increased level of serum amylase and lipase (more than 3-fold) Returns to normal after 3-7 days Amylase elevations in serum and urine occur in many conditions other than pancreatitis Acute pancreatitis: increased level of serum amylase and lipase (more than 3-fold) Preferred test (more specific than amylase) Elevated for 7-14 days Leukocytosis (15,000-20,000/uL) Hemoconcentration with hematocrit values >44% Azotemia with BUN > 22mg/dL: due to loss of plasma into the retroperitoneal space and peritoneal cavity Hyperglycemia: due to decreased insulin release, increased glucagon release, increase output of adrenal glucocorticoids and catecholamines Hypocalcemia: saponification Hyperbilirubinemia Serum alkaline phosphatase and aspartate aminotransferase levels are transiently elevated Markedly elevated serum LDH levels: poor prognosis Hypertriglyceridemia Hypoxemia (arterial PO2 < 60 mmHg): may herald the onset of ARDS Helpful in indicating the severity of acute pancreatitis and the risk of morbidity and mortality Aids in evaluating for complications of acute pancreatitis Useful in acute pancreatitis to evaluate the gallbladder if gallstone disease is suspected

IV. DEFINING SEVERE ACUTE PANCREATITIS RISK FACTORS FOR SEVERE DISEASE  Age > 60 years  Obesity, BMI >30  Comorbid disease (Charlson Comorbidity Index)     

 

MARKERS OF SEVERITY AT ADMISSION OR WITHIN 24 HOURS SIRS APACHE II Hemoconcentration (Hematocrit > 44%) Admission BUN (>22 mg/dL) BISAP (> 3 of these factors: associated with increased risk for in-hospital mortality) o B: BUN >25 mg/dL o I: Impaired Mental Status (GCS 2 of 4 present o A: Age > 60 years o P: Pleural effusion Organ Failure (Modified Marshall Score) o Cardiovascular: SBP < 90 mmHg, HR > 130 bpm o Pulmonary: PaO2 < 60 mmHg o Renal: serum creatinine > 2.0 mg/dL MARKERS OF SEVERITY DURING HOSPITALIZATION Persistent organ failure (>48 hours) Pancreatic necrosis

V. MANAGEMENT  Usually, the disease is self-limited and subsides spontaneously  Resolution occurs within 3-7 days after treatment is instituted Conventional  Analgesics for pain Measures  No oral alimentation (NPO) Fluid Resuscitation  The most important treatment intervention: safe, aggressive IV fluid resuscitation


  Antibiotics ERCP Resumption of Diet

    

Initial IVF: LR or pNSS at 15-20 cc/kg bolus, followed by 3mg/kg/hr to maintain urine output >0.5cc/kg/hr Targeted resuscitation strategy: measure hematocrit and BUN every 8-12 hours to ensure adequacy of fluid resuscitation and monitor response to therapy Prophylactic antibiotics have no role in either interstitial or necrotizing pancreatitis For severe acute biliary pancreatitis with organ failure and/or cholangitis No abdominal pain, nausea or vomiting Patient is hungry Normal bowel sounds

VI. COMPLICATIONS LOCAL COMPLICATIONS Necrosis (sterile or infected) Pancreatic fluid collections (pseudocyst, abscess) Pancreatic ascites Obstructive jaundice

SYSTEMIC COMPLICATIONS Pulmonary: ARDS, effusion, pneumonitis Cardiovascular: hypotension, sudden death Hematologic: disseminated intravascular coagulation Gastrointestinal: ulcer formation, gastritis Renal: oliguria, azotemia, acute tubular necrosis Metabolic: hyperglycemia, hypocalcemia

SURGICAL CAUSES OF RIGHT UPPER QUADRANT PAIN I. DIFFERENTIALS FOR RIGHT UPPER QUADRANT PAIN DIFFERENTIAL DESCRIPTION  Divided into two major types: Cholelithiasis o Cholesterol stones (80%) (“Gallstones”) o Pigment stones (< 20%)  Ultrasonography: very accurate in the identification of cholelithiasis  Most specific and characteristic symptom of gallstone disease: biliary colic  Passage of stones in the common bile duct (CBD)  CBD stones should be suspected in gallstone patients who have any of the following Choledocholelithiasis risk factors: o History of jaundice or pancreatitis o Abnormal tests of liver function o Ultrasonographic or MRCP evidence of a dilated CBD or stones in the duct  Acute inflammation of the gallbladder wall usually follow obstruction of the cystic duct by a stone Acute Cholecystitis  Ultrasonography demonstrates calculi in 90-95% and is useful for detection of signs of gallbladder inflammation: thickening of the wall, pericholecystic fluid and dilation of the bile duct  Bacterial infection superimposed on an obstruction of the biliary tree most commonly Ascending Cholangitis from a gallstone  Medical +/- surgical emergency II. CLINICAL MANIFESTATIONS OF BILIARY TRACT PATHOLOGIES  Most specific and characteristic symptom of gallstone disease  Steady epigastric or RUQ pain, radiation to intrascapular area, right scapula or shoulder  Begins quite suddenly and may persist with severe intensity for 15 minutes to 5 hours Biliary colic  Subsides gradually or rapidly  Persistence of pain beyond 5 hours should raise the suspicion of acute cholecystitis  May be precipitated by: o Eating a fatty meal o Consumption of a large meal following a period of prolonged fasting o Eating a normal meal Murphy’s sign  Deep inspiration or cough during subcostal palpation of the RUQ usually produces increased pain and inspiratory arrest


Mirizzi’s Syndrome

  

Courvoisier’s Law

Triad of Acute Cholecystitis

             

Charcot’s Triad of Acute Cholangitis

Reynolds’ Pentad of Acute Cholangitis

Other symptoms

III. DIAGNOSTICS Bilirubin, Alkaline Phosphatase Gallbladder Ultrasound

Usually in acute cholecystitis Rare complication Gallstone becomes impacted in the cystic duct or neck of the gallbladder causing compression of the common bile duct (CBD), resulting in CBD obstruction and jaundice A palpable enlarged gall bladder suggests that the biliary obstruction is secondary to underlying malignancy Sudden RUQ tenderness Fever Leukocytosis Biliary (RUQ) pain Jaundice Spiking fevers with chills Biliary (RUQ) pain Jaundice Fever Shock Altered mental status Nausea and vomiting Jaundice usually if with CBD obstruction Fever or chills with biliary pain imply a complication: cholecystitis, pancreatitis, cholangitis 

Elevated levels suggest common bile duct stone

   

Rapid, accurate identification of gallstones (>95%) Procedure of choice for detection of stones Limitations: bowel gas, massive obesity, ascites Pathognomonic findings in: o Calcified gallstones o Limey bile, porcelain GB o Emphysematous cholecystitis o Gallstone ileus Limitations: generally low-yield; contraindicated in pregnancy Useful modality for visualizing pancreatic and biliary ducts Cannot offer therapeutic intervention

Plain Abdominal X-Ray

Magnetic Resonance Cholangiopancreatography (MRCP) Endoscopic Retrograde Cholangiopancreatography (ERCP) Pecutaneous Transhepatic Cholangiogram

        

Best visualization of distal biliary tract Cholangiogram of choice in: absence of dilated ducts, pancreatic or ampullary disease, prior biliary surgery, endoscopic sphincterotomy is a treatment possibility Can be complicated by pancreatitis, cholangitis or perforation Best visualization of proximal biliary tract Can provide biliary of drainage Indicated when ERCP is contraindicated or has failed

IV. MANAGEMENT A. Cholelithiasis (Gallstones)  Laparoscopic cholecystectomy: “gold standard” for treating symptomatic cholelithiasis  Ursodeoxycholic acid (UDCA) 10-15 mg/kg per day o Used for cholesterol stones: therapy should be limited to radiolucent stones 40 mL/min)

CEPHALOSPORINS First-Generation: Active against most gram-positive cocci including penicillin-resistant S. aureus but not against enterococcus, Methicillinresistant S. aureus (MRSA) and Methicillinresistant S. epidermidis (MRSE)

Cefazolin Cephalexin Cephalothin Cefadroxil Cephapirin

Second-Generation: Cefoxitin Cefaclor Cefuroxime Cefamandole Cefonizid Cefotetan Cefprozil

Inhibit cell wall synthesis, but are less susceptible to penicillinase

Prophylaxis for Cardiovascular and General Surgeries (Biliary Tract, Esophageal, Appendectomy or Laparoscopic Surgery): Usually Cefazolin 1-2 g IV preop (single dose) Respiratory infections: Cephalexin 250 mg PO q6

Cefoxitin – resistant to beta-lactamaseproducing gram-negative bacilli Improved activity against H. influenza, M. catarrhalis, Neisseria meningitides and N. gonorrhea Enhanced activity against staphylococci, non-enterococci streptococci and some Enterbacteriaceae

Prophylaxis for NonPerforated Appendicitis: Cefoxicillin 1-2 g IV pre-op Pharyngitis/Tonsillitis: Cefuroxime 250 mg PO q12 for 10 days



Effective against S. pneumoniae, S. pyrogenes and other streptococci (with the exception of Ceftazidime) and have modest activity against Methicillin-sensitive S. aureus (MSSA)

Ceftriaxone Ceftazidime Cefixime Ceftizoxime Cefpodoxime proxetil Cefotaxime Cefoperazone Moxalactam

Excellent activity against N. gonorrhea, H. influenza, M. catarrhalis and Enterobacteriaceae Active against both aerobic gram-positive organisms (but not MRSA) and gramnegative organisms, including P. aeruginosa

Fourth-generation: (widest spectrum) Cefepime Cefpirome

CAP Mod risk: Ceftriaxone 2g IV q24 CAP High risk + Risk for P. aeruginosa infection: Ceftazidime 2 g Iv q8

CAP High risk + Risk for P. aeruginosa infection: Cefepime 1-2 g IV q8-12 up to 21 days

Inactive against MRSA, MRSE, Enterococcus sp., B. fragilis and ESBL Specifically developed to target resistant strains of bacteria Ceftobiprole – active against MRSA, Penicillin-resistant S. pneumoniae, P. aeruginosa and enterococci

Fifth-generation: Ceftobiprole Ceftaroline fosamil

Ceftaroline fosamil – for acute bacterial skin and skin structure infections (ABSSSI) caused by MSSA, MRSA, S. pyrogenes, E. coli, K. pneumoniae and CAP caused by S. pneumoniae, S. aureus, H. influenxa, K. pneumoniae and E. coli

Skin & soft tissue infections: Ceftobiprole 500 mg IV infusion q12


Meropenem Imipenem Doripenem Ertapenem

Inhibit cell wall synthesis, and are highly resistant to degradation by beta-lactamases

Nosocomial infections caused by multipleresistant and complicated polymicrobial infections caused by aerobic gram-positive, gram-negative organisms, anaerobic bacteria and ESBL-positive organisms. All are recommended for pseudomonal infections except Ertapenem

Intraabdominal infections: Meropenem 1 g IV q8; Imipenem 500 mg IV q6 or 1 g IV q8 for 4-7 days Complicated skin/skin structure infections: Meropenem 500 mg IV q8


Inhibit cell wall synthesis (binds to PBP3)

Activity limited to gram-negative bacilli including most Enterobacteriaceae, Aeromonas sp., N. gonorrhea, H. influenza and P. aeruginosa



Inhibit formation of initiation complex and cause misreading of mRNA (30S inhibitor)


Active against aerobic gram-negative bacilli; most are active against P. aeruginosa, E. coli, Klebsiella and Proteus sp. Synergistic against staphylococcal, streptococcal and enterococcal endocarditis

Pseudomonal infections: Aztreonam 2 g IV/IM q6-8


Prophylaxis for Colorectal Surgery: Neomycin + Erythromycin base 1 g each PO at 1, 2, and 11 pm on the day before surgery or Neomycin 2 g + Metronidazole 2 g at 7 and 11 pm on the day before surgery



Amikacin Streptomycin Tobramycin Kanamycin Netilmycin

Inhibit formation of initiation complex and cause misreading of mRNA (30S inhibitor)

III. BETA-LACTAMASE INHIBITORS EXAMPLES MECHANISM OF ACTION Clavulanic acid (usually with Inhibits betaAmoxicillin, Ticarcillin) lactamases which then restores the Sulbactam antibacterial (usually with activity of Ampicillin) amoxicillin, ampicillin, Tazobactam ticarcillin and (usually with piperacillin Piperacillin) IV. CHLORAMPHENICOL EXAMPLES MECHANISM OF ACTION

Active against aerobic gram-negative bacilli; most are active against P. aeruginosa, E. coli, Klebsiella and Proteus sp. Useful combination treatment for serious gram-negative infections Synergistic against Staphylococcal, Streptococcal and Enterococcal endocarditis


Against Beta-lactamase producing strains of staphylococci, gonococci, H. influenza, M. catarrhalis, Bacteroides, Klebsiella sp. and E. coli


In addition to an antipseudomonal betalactam or carbapenem in HAP: Amikacin 20 mg/kg/day IV Tuberculosis: Streptomycin 15 (12-18) mg/kg IM per day (max 1 g/day)


Exacerbation of chronic bronchitis: Co-amoxiclav 1 g BID Severe infections; Nosocomial Pneumonia: Piperacillin/Tazobactam 4.5 g IV q6 (CrCl >40 mL/min)

COMMON DOSAGES Fully susceptible typhoid:



Inhibition of peptide bond formation at the 50S subunit


Aerobic and anaerobic bacteria Standard therapy for typhoid fever, ampicillinresistant H. influenza and intraocular infections


Uncomplicated: 50-75 mg/kg x 14-21 days

COMMON DOSAGES Acute bronchitis: Azithromycin 500 mg PO BID day 1 then 250 mg PO OD for days 2-5


Prevents translocation at the 50S subunit


Severe and complicated: 100 mg/kg IV x 14-21 days

Active against aerobic gram-positive cocci and bacilli, Legionella, Mycoplasma, Chlamydia and some gram-negative organisms including Bordetella pertussis, H. ducreyi and C. jejuni

Cervicitis; Chancroid: Azithromycin 500 mg PO single dose Chancroid: Erythromycin 500 mg PO QID for 7 days Alternative for nongonococcal urethritis: Erythromycin base 500 mg PO QID for 7 days; Erythromycin ethylsuccinate 800 mg PO QID for 7 days


Exacerbation of chronic bronchitis: Clarithromycin 500 mg PO BID for 7 days

Newer Macrolides Clarithromycin Roxithromycin Josamycin Telithromycin Fidaxomicin

H. pylori: (together with Bismuth and Amoxicillin) Clarithromycin 500 mg BID for 2 weeks

VI. GLYCOPEPTIDES EXAMPLES MECHANISM OF ACTION Inhibit cell wall mucopeptide Vancomycin formation by binding D-ala Dala portion cell wall precursors VII. LINCOSAMIDES EXAMPLES



Active against MSSA, MRSA, coagulasenegative staphylococci, enterococci, streptococci, C. diphtheria (JK Group), C. difficile and Listeria


COMMON DOSAGES MRSA Infections: Vancomycin 15-20 mg/kg IV q12 (adjust accordingly based on creatinine clearance)

COMMON DOSAGES CA MRSA: Clindamycin 600 mg IV q6-8

Clindamycin Lincomycin

Blocks peptide bond formation at 50S ribosomal subunit

Useful for aerobic and anaerobic gram-positive cocci, some anaerobic gram-negative bacilli and protozoans

Bacterial vaginosis: Clindamycin cream 2%, 1 full applicator (5g) intravaginally HS for 7 days Alternative: Clindamycin 300 mg PO BID for 7 days or Clindamycin ovules 100 mg intravaginally HS for 3 days Add-on therapy to Aspiration Pneumonia (except in B-lactams that already have anaerobic activity): Clindamycin 450-900 mg IV q8



COMMON DOSAGES Bacterial Vaginosis: Metronidazole 500 mg PO BID for 7 days or Metronidazole gel 0.75%, 1 full applicator (5 g) intravaginally OD for 7 days

Metronizadole Secnidazole

Forms toxic metabolites in the bacterial cell that damage DNA

Excellent activity against anaerobes and protozoans

Trichomoniasis: Metronidazole 2 g PO SD Alternative: Metronidazole 500 mg BID x 7 days Acute gastroenteritis by B. hominis: Metronidazole 750 mg PO TID x 10 days Pseudomembranous colitis (C. difficile): Metronidazole 500 mg PO TID for 10 days


IX. OXAZOLIDINONES EXAMPLES MECHANISM OF ACTION Protein synthesis Linezolid inhibitors: disrupts mRNA translation X. QUINOLONES EXAMPLES




Active against S. aureus, S. epidermidis, S. pneumoniae, E. faecalis, and E. faecium


Soft tissue infections: Linezolid 600 mg PO/IV q12


First Generation: Usually for UTI and diarrheal diseases among children

Cinoxacin Nalidixic acid Oxolinic acid Pipemidic acid

Second Generation: Ciprofloxacin Norfloxacin Ofloxacin Lomefloxacin Pefloxacin Rufloxacin

Blocks bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV

Active against Enterobacteriaceae and Haemophilus sp., N. gonorrhea & M. catarrhalis, C. trachomatis, and H. ducreyi

Broadened activity against anaerobes, intracellular pathogens & some gram-positive and gram-negative aerobes

Third Generation: Levofloxacin

Not available locally

Alternative for acute uncomplicated cystitis: Ciprofloxacin 250 mg BID PO for 3 days; Norfloxacin 400 mg BID PO for 3 days Primary treatment for uncomplicated acute pyelonephritis: Ciprofloxacin 500 mg BID for 7-10 days Salmonella gastroenteritis: Ciprofloxacin 500 mg PO OD for 7-10 days Shigellosis: Ciprofloxacin 750 mg PO OD for 3 days Add-on to an IV non-antipseudomonal betalactam in Moderate or High Risk CAP: Levofloxacin 500 mg PO/IV OD for 7-14 days or 750 mg PO/IV for 5 days Primary treatment for uncomplicated acute pyelonephritis: Levofloxacin 250 mg OD PO for 7-10 days or 750 mg OD PO for 5 days Salmonella gastroenteritis: Levofloxacin 500 mg PO OD x 7-10 days

Highly effective against both typical and atypical respiratory pathogens

Fourth Generation: Moxifloxacin Gatifloxacin


Nitrofurantoin Nifuroxazide Furazolidone

Moxifloxacin – most potent against S. pneumoniae

MECHANISM OF ACTION Inactivates bacterial ribosomal proteins and other macromolecules

Add-on to an IV non-antipseudomonal betalactam in Moderate or High Risk CAP: Moxifloxacin 400 mg PO/IV OD x 10 days



Usually for the treatment of uncomplicated lower UTI

Acute uncomplicated cystitis: Nitrofurantoin monohydrate 100 mg BID PO x 5 days or Nitrofurantoin macrocrystals 100 mg QID PO x 5 days


resulting to inhibition of DNA, RNA, protein and cell wall synthesis XII. TETRACYCLINES EXAMPLES MECHANISM OF ACTION

Doxycycline Minocycline Oxytetracycline Tetracycline Tigecycline

Binds to 30S subunit to block binding of aminoacyl-tRNA to acceptor site ribosome-mRNA complex

XIII. TRIMETHOPRIM/SULFONAMIDES EXAMPLES MECHANISM OF ACTION Cotrimoxazole: TrimethoprimSulfamethoxazole Folic acid (TMP-SMX) synthesis inhibitors Cotrimazine: TrimethoprimSulfadiazine

ORGANISMS COVERED Drug of choice for V. cholera, V. vulnificus, B. burgdorferi, some Aeromonas and Xanthomas sp., Mycoplasmas Penicillin allergic patients with leptospirosis, syphilis, actinomycosis, tularemia, meliodosis and skin and soft tissue infections


Cervicitis/Nongonococcal urethritis/ Chlamydia infections: Doxycycline 100 mg PO BID x 7days Donovanosis: Doxycycline 100 mg PO BID x 3-4 weeks until all lesions have completely healed Lymphogranuloma venereum: Doxycycline 100 mg PO BID x 21 days

ORGANISMS COVERED Excellent activity against S. typhi, some strains of Shigella, V. cholera, H. influenza

COMMON DOSAGES Pneumocystitis jiroveci Pneumonia For prophylaxis: TMP-SMX 160/800 mg 3x weekly, or TMP-SMX 80/400 mg PO OD

Use in Pneumocystitis jiroveci infection

For treatment: TMP-SMX 15-20 mg TMP/kg/day PO or IV q6-q8


Any febrile illness without an initially obvious etiology The term FUO should be reserved for prolonged febrile illness without an established etiology, despite intensive evaluation & diagnostic testing TYPE DEFINITION Fever of Unknown Origin  Temperature > 38.3oC on several occasions (Petersdorf & Beeson Definition 1961)  Duration of fever > 3 weeks on two occasions  Uncertain diagnosis despite 1 week of inpatient investigation  Fever > 38.3oC on at least two occasions  Illness duration of > 3 weeks  No known immunocompromised state  Diagnosis uncertain after a thorough history-taking, physical exam and the following obligatory investigations: o ESR, CRP Recent Definition of FUO o Platelet count, leukocyte count and differential, hemoglobin o Electrolytes, creatinine, total protein o Alkaline phosphatase, ALT, AST o LDH, creatinine kinase o Ferritin o ANA and RF o Protein electrophoresis


o o o o

Urinalysis Blood culture (x3), urine culture Imagine (CXR and abdominal ultrasound) Tuberculin skin test


Infectious diseases associated with a rash DISEASE ETIOLOGY

Rubeola: Measles (1st disease)


Scarlet fever (2nd disease)

Group A Streptococcus (pyrogenic exotoxin A, B, C)

Rubella: German Measles (3rd disease) Erythema infectiosum (5th disease) Exanthema subitum: Roseola (6th disease) Infectious Mononucleosis


Human parvovirus B19

DESCRIPTION  Begins as erythematous macules behind the ears, neck and hairline then progresses to face, trunk and extremities  Koplik’s spots: pathognomonic for measles; bluish white dots surrounded by erythema; appears first on the buccal mucosa opposite the lower molars  Rash is made up of minute papules giving the “sandpaper” feel of the skin  Pastia’s lines: accentuation of the rash in skin folds  Spreads from hairline downward, with clearing as it spreads  Forschheimer spots: petechiae on the soft palate, present in 20% of patients  Erythematous macular rash that spreads to the extremities in a lacy reticular pattern “Slapped-cheeks” disease; “Glove-and-socks” syndrome  Diffuse maculopapular rash over trunk and neck

Human herpesvirus 6

Epstein-Barr virus

Epidemic Typhus

Rickettsia prowazekii

Endemic (Murine) Typhus

Rickettsia typhi

Scrub Typhus

Orientia tsutsugamushi


Leptospira interrogans

Lyme Disease

Borrelia burgdorferi

Typhoid Fever

Salmonella typhi

Dengue Fever

Dengue virus (4 serotypes; flavivirus)

Relapsing Fever

Borrelia species

African Trypanosomiasis

Trypanosoma rhodesiense (East Africa)/ gambiense (West Africa)

Secondary Syphilis

Treponema pallidum

 5% of patients develop morbilliform or popular rash usually on the arms and trunk  Most patients given ampicillin may develop a macular rash  Macular rash usually presents on the fifth day, begins on the upper trunk and becomes generalized sparing the face, palms and soles  Initial macular rash usually detected in the axilla or inner arm  Most patients given ampicillin may develop a macular rash  Maculopapular rash and presence of the characteristic eschar (site where the chigger has fed)  Rash may be macular, maculopapular, erythematous, petechial or ecchymotic  Presence of erythema migrans (central clearing, red outer border and a target center) at the site of tick bite  Rose spots: faint, salmon-colored, blanching maculopapular rash usually seen on the trunk and chest  Maculopapular rash beginning on the trunk and spreads to the extremities and face which usually presents near the time of defervescence  Petechiae on the trunk, extremities and mucous membranes seen in 18% of patients at the end of febrile episode  Blotchy or erythematous maculopapular rash on the trunk  Presence of a painful trypanosomal chancre in some patients at the site of inoculation  Initially pale red or pink macules on the trunk and proximal extremities which progresses to popular lesions usually on the palms and soles  Condyloma lata: papules that enlarged to form broad,


Chikungunya Fever

Chikungunya virus

Hand-Foot-andMouth Disease

Coxsackie virus A16 (most common cause) Group A streptococcus (associated with pyrogenic exotoxin A and/or B or certain M types) S. aureus (toxic shock syndrome toxin 1, enterotoxin B or C)

Streptococcal Toxic Shock Syndrome Staphylococcal Toxic Shock Syndrome Staphylococcal Scalded-Skin Syndrome Varicella: Chickenpox Pseudomonas “hottub” folliculitis Primary Herpes Simplex Virus (HSV) infection

Acute Meningococcemia

S. aureus, phagr group II Varicella-zoster virus Pseudomonas aeruginosa


Neisseria meningitides

Chronic Meningococcemia Tularemia

Neisseria meningitides


Bacillus anthracis

Francisella tularensis

moist, pink or gray-white highly infectious lesions usually in warm, intertriginous areas  Maculopapular rash on upper extremities and face, appearing at the time of defervescence  Painful vesicles in the mouth; papules on hands and feet  Scarlatiniform rash  Erythroderma of variable intensity  Desquamation of the skin occurs during convalescence  Localized blister formation and exfoliation of the skin  Nikolsky’s sign: rupture of the lesions with gentle pressure  Macules evolving into papules then vesicles on an erythematous base (the classic “dew on a rose petal”)  Pruritic erythematous follicular, popular, vesicular or pustular lesions  Hallmark: painful grouped vesicles that may progress to pustules and ulcerate  Initially pink maculopapular lesions and later evolves into nonblanching petechial rash usually in the trunk and extremities  May have purpura fulminans (large ecchymoses with sharply irregular shapes evolving into hemorrhagic bullae and then into black necrotic lesions; reflects disseminated intravascular coagulation)  May have pink maculopapular, nodular, petechial and purpuric lesions with pale blue-gray centers; recurrent  Ulceroglandular form: erythematous, tender papule evolves into necrotic, tender ulcer with raised borders  Typically begins as a papule which evolves to a painless vesicle then later on to a coal-black, necrotic eschar



COMMON INFECTIOUS DISEASES CONDITIONS DENGUE I. ETIOPATHOGENESIS  Acute febrile illness of 2-7 days duration (sometimes biphasic), with no identifiable focus of infection  Four (types 1 to 4) distinct viruses (type 2 is more dangerous)  Principal vector: Aedes aegypti, which breeds near human habitation  Macrophage/monocyte infection is central to the pathogenesis  Second infection with a serotype different from that involved in the primary infection leads to dengue hemorrhagic fever (HF) with severe shock  Incubation period: 2-7 days II. CLINICAL MANIFESTATIONS  Classic symptoms: sudden onset of fever, headache, retro-orbital pain, and back pain along with severe myalgia  “break-bone fever”  Initial symptoms: macular rash, adenopathy, palatal vesicles and scleral injection  Other signs and symptoms: anorexia, nausea, vomiting, cutaneous hypersensitivity, maculopapular rash beginning on the truck and spreading to extremities and face  Epistaxis and scattered peterchiae are often noted in uncomplicated dengue and preexisting gastrointestinal lesions may bleed during the acute illness III. DIAGNOSIS A. Common Diagnostic Tests DIAGNOSTICS Complete blood count Dengue IgM and IgG (ELISA)

NS1 Antigen (Rapid) Test

     

Tourniquet test 

COMMENTS/EXPECTED FINDINGS Leukopenia, thrombocytopenia, elevated hematocrit IgM antibody: usually detected by day five of illness IgG antibody: detects past dengue infection Immunoassay for the detection of non-structural protein 1 (NS1) antigens Aids in screening and diagnosis as early as 1 day post-onset of symptoms (prior to the detection of IgM or IgG antibodies) BP cuff is inflated midway between systolic and diastolic pressures for 5 minutes Considered positive if >20 petechiae per square inch, 1.5 inches from the volar aspect of the antecubital fossa

B. WHO Classification of Dengue DENGUE + WARNING SIGNS DENGUE FEVER WARNING SIGNS Probable Dengue  Abdominal pain or Lives in/travels to dengue endemic area tenderness Fever and any 2 of the following:  Persistent vomiting  Nausea, vomiting  Clinical fluid collection  Rash  Mucosal bleed  Aches and pains  Lethargy, restlessness  Positive Tourniquet test  Liver enlargement >2 cm  Leukopenia  Increase in Hct concurrent  Any warning signs with rapid decrease in platelet count Laboratory-Confirmed Dengue  Important when there are no signs *requiring strict observation and of plasma leakage medical intervention

SEVERE DENGUE Severe Plasma Leakage  Leads to shock accumulation with distress

and fluid respiratory

Severe Bleeding  As evaluated by physician Severe Organ Involvement  Liver: AST or ALT > 1000  CNS: impaired consciousness  Heart and other organs


IV. MANAGEMENT GROUP A DENGUE FEVER WITHOUT WARNING SIGNS May be sent home Advise:  Adequate bed rest  Adequate fluid intake  Paracetamol PRN (4g max per day) Patients with stable hematocrit can be sent home; advise return to hospital if with development of warning signs Daily review for disease progression: decreasing WBC, defervescence, warning signs until out of critical period

GROUP B DENGUE FEVER WITH WARNING SIGNS Patients with co-existing conditions* and have social circumstances** Referred for in-patient management Hydration:  Encourage OFI if tolerated. If not, start IVF  Start with 5-7 ml/kg/hr for 1-2 hrs  Reduce to 3-5 ml/kg/hr for 2-4 hrs  Reduce to 2-3 ml/kg/hr or less according to clinical response o If Hct remains the same or rises minimally, continue with 2-3 ml/kg/hr for another 2-4 hrs o If with worsening of vitals and rapidly rising Hct, increase rate to 5-10 ml/kg/hr for 1-2hrs  Reduce IVF until adequate UO and/or fluid intake or Hct decreases below baseline value Monitoring  VS q1-4 hrs until out of critical phase  Hct at baseline and q6-12 hrs  Blood glucose and other organ function tests


Require emergency treatment Initial resuscitation: isotonic crystalloid solutions at 5-10 ml/kg/hr over 1 hour  If patient improves: IVE may be reduced to 5-7 ml/kg/hr for 1-2 hours, 3-5 ml/kg/hr for 2-4 hrs and then reduced further depending on hemodynamic status; IVF can be maintained over 24 to 48 hrs  If unstable: recheck Hct after 1st IV bolus o If Hct increases/still high (>50%), repeat a second bolus of crystalloid solution or 10-20 ml/kg/hr for 1 hour (if there is improvement, reduce rate to 7-10 ml/kg/hr and continue to reduce as above) o If Hct decreases, this indicates bleeding and need to cross-match & transfuse Treatment of hypotensive shock: initiate resuscitation with crystalloid or colloid solution at 20 ml/kg as bolus for 15 mins  If patient improves, give IVF at 10 ml/kg/hr for 1 hr then reduce gradually  If still unstable: review Hct, assess need for further fluid resuscitation (if persistently high) or need for bllod transfusion Treatment of hemorrhagic complications: Give 5-10 ml/kg of pRBC or 10-20 ml/kg fresh whole blood

*such as pregnancy, infancy and old age, obesity, diabetes, renal failure, chronic hemolytic disease, etc. **such as living alone, or living far from health facilities


MALARIA I. ETIOPATHOGENESIS A. Pathogenesis  Most important parasitic disease in humans  In humans, the erythrocytic cycle is responsible for disease o Rupture of schizonts and release of merozoites present clinically as paroxysms of malaria o Hypnozoites are responsible for disease relapses B. Etiology  Protozoan disease caused by 4 species of Plasmodium (falciparum, vivax, ovale and malariae) and transmitted by the bite of infected Anopheles mosquitoes (Anopheles flavirostris in the Philippines)  Plasmodium falciparum causes nearly all deaths and neurological complications II. CLINICAL MANIFESTATIONS A. Classic Malaria Paroxysm: cold stage (chills), hot stage (fever spikes), sweating stage Tertian Periodicity Plasmodium falciparum (malignant tertian) Cyclic fever occurring Plasmodium vivac, ovale (benign tertian) every 48 hours Quartan Periodicity Plasmodium malariae Cyclic fever occurring every 72 hours B. Symptoms Ranging from Mild Constitutional Symptoms to Organ Failure MILD / NON-LIFE THREATENING MALARIA SEVERE FALCIPARUM MALARIA  Unarousable coma / cerebral malaria  Academia / acidosis  Nonspecific constitutional symptoms  Severe normochromic, normocytic anemia  Headache without neck stiffness or photophobia  Renal failure  Nausea and vomiting  Pulmonary edema / ARDS  Classic malaria symptoms  Hypoglycemia  Anemia  Hypotension / shock  Hepatosplenomegaly  Bleeding / disseminated intravascular coagulation  Mild jaundice (DIC)  Convulsions  Others: hemoglobinuria, extreme weakness, hyperparasitemia, jaundice III. DIAGNOSIS OF MALARIA DIAGNOSTICS  

Microscopic Examination Complete blood count (CBC) Blood chemistry

ABG PT/PTT Lumbar tap cerebral malaria)

   


COMMENTS/EXPECTED FINDINGS Thick and thin smear: gold standard for laboratory confirmation of Malaria Acute demonstration of the parasite in the smear o Thick smear: for quantification of parasitemia o Thin smear: for species identification Normocytic normochromic anemia, thrombocytopenia Decreased plasma glucose, ↓Na, ↓HCO3, ↓Ca2+, ↓phosphate, ↓albumin, ↑lactate, ↑BUN, ↑creatinine, ↑urate, ↑muscle & liver enzymes, ↑bilirubin (DB & IB) Metabolic acidosis (usually high anion gap) Prolonged in severe cases Mean opening pressure ~180 mmHg of CSF Normal or slightly ↑total protein and cell count

IV. MANAGEMENT OF MALARIA A. Malaria is treated with Combination Drugs (due to widespread chloroquine resistance) DRUG REGIMEN CLINICAL USE SIDE EFFECTS Chloroquine + Sulfadoxine  First line of treatment in  Pyrimethamine: megaloblastic


Pyrimethamine (CQ + SP)  Artemether-Lumefantrine 

Quinine + Tetracycline/ Doxycycline (Quinine + Clindamycin for pregnant women and children 12,000 with neutrophilia and thrombocytopenia  Serum creatinine >3 mg/dL (or CrCl 23 mg/dL  AST/ALT ratio >4x, Bilirubin >190 umol/L  Prolonged PT 4 mmol/L  ABG: severe metabolic acidosis (pH 70 years  Incubation period < 7 days  Short time from first symptom to admission  Puerperal, IV, post-surgery and burn entry site  Period of onset < 48 hours  HR >140 bpm  SBP >14 mmHg  Severe disease or spasms  Temperature >38.5oC

RABIES I. ETIOPATHOGENESIS  Rapidly progressive, acute infectious disease of the CNS, caused by the rabies virus (family Rhabdoviridae)  Incubation: 20-90 days  Transmission: via bite of an infected animal  Prognosis: recovery is rare II. CLINICAL MANIFESTATIONS  Encephalithic (Furious) Rabies (80%

Paralytic Rabies (20%)

 

Combativeness, seizures, autonomic dysfunction (hypersalivation, gooseflesh, cardiac arrhythmia, priapism) Hydrophobia: involuntary, painful contraction of the diaphragm and accessory respiratory/laryngeal/pharyngeal muscles in response to swallowing liquids Aerophobia: same features cause by stimulation from a draft of air Early and prominent flaccid muscles weakness predominates

III. CATEGORIZATION OF EXPOSURE AND RESPECTIVE MANAGEMENT (WHO CLASSIFICATION) EXPOSURE MANAGEMENT  Feeding/touching an animal  Wash exposed skin immediately with soap and water  Licking of intact skin


 Exposure to patient with signs of rabies by sharing or eating or drinking utensils  Casual contact with patient with signs of rabies




 Nibbling/nipping of uncovered skin with bruising  Minor scratches / abrasions / abrasions without bleeding (includes wounds that are induced to bleed)  Licks on broken skin

 Transdermal bites or scratches (includes puncture wounds, lacerations and abrasions)  Contamination of mucous membranes with saliva (e.g., licks)  Exposure to rabies patient through bites, contamination of mucous membranes or open skin lesions with body fluids (except blood/ feces) through splattering, mouth-to-mouth resuscitation, licks of eyes, lips, vulva, sexual activity, exchanging kisses on the mouth or other direct mucous membrane contact with saliva  Handling of infected carcass or ingestion of raw infected meat

 No vaccine or RIG needed  Pre-exposure vaccination may be considered  Start vaccine immediately o Complete regimen until day 28/30 if:  Animal is rabid, killed, died or unavailable for 14 day observation and examination; or  Animal under observation died within 14 days and was IFAT positive or no IFAT testing was done or has signs of rabies o Complete vaccine regimen until:  Animal is alive and remains healthy after 14day observation period  Animal under observation died within 14 days but had no signs of rabies and was IFAT negative  Start vaccine and RIG immediately: o Complete regimen until day 28/30 if:  Animal is rabid, killed, died or unavailable for 14 day observation and examination; or  Animal under observation died within 14 days and was IFAT positive or no IFAT testing was done or had signs of rabies o Complete vaccine regimen until day 7 if:  Animal is alive & remains healthy after 14 day observation period  Animal under observation died within 14 days but had no signs of rabies and was IFAT negative

INFECTIVE ENDOCARDITIS (IE) I. ETIOPATHOGENESIS  Prototypic lesion: vegetation  The analogous process involving AV shunts, PDAs or coarctation of the aorta is called infective endarteritis  Endothelial injury may also lead to development of an uninfected platelet-fibrin thrombus called non-bacterial thrombotic endocarditis (NBTE) or as a result of a hypercoagulable state called marantic endocarditis II. DIAGNOSIS: THE MODIFIED DUKE’S CRITERIA A. Criteria for Diagnosis Definite Endocarditis Possible Endocarditis

Diagnosis of IE is Rejected

       

Two major criteria; or One major criteria and three minor criteria; or Five minor criteria One major + one minor, or Three minor criteria Alternative diagnosis is established Symptoms resolved & do not recur with < 4 days of antibiotic therapy Surgery or autopsy after < 4 days of antimicrobial therapy yields no histologic evidence of endocarditis

B. Major and Minor Criteria (from the Modified Duke’s Criteria)  Blood cultures: three 2-bottle sets separated from one another by at least 1 hour and obtained from different sites over 24 hours  If cultures remain negative after 48-72 hours, 2 to 3 additional blood culture sets should be obtained  Predisposing heart conditions include: valvular disease with stenosis or regurgitation, prosthetic valves, congenital heart defects, prior endocarditis, hypertrophic cardiomyopathy


MAJOR CRITERIA 1) Positive blood culture:  Typical organisms for IE from >2 cultures: o S. viridans o HACEK o S. gallolyticus (previously S. bovis) o S. aureus o Enterococcus  OR, Persistently positive, defined as recovery of a microorganism consistent with IE from: o Blood cultures drawn >12 hours apart, or o All of 3 or a majority of >4 separate cultures with first and last drawn at least 1 hour apart  OR, Single positive blood culture for Coxiella burnetii or phase I IgG antibody titer of >1:800 2) Evidence of endocardial involvement:  Positive echocardiogram: o Oscillating intracardiac mass o Abscess o New dehiscence of prosthetic valve  Or, New valvular regurgitation

MINOR CRITERIA Predisposing heart condition injection drug use

Fever > 38.0oC

Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysms, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions

Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, rheumatoid factor

Microbiologic evidence: positive blood culture but not meeting major criterion or serologic evidence of active infection with organism consistent of IE


*HACEK: Haemophilius sp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella sp.

III. CLINICAL MANIFESTATIONS A. Acute Versus Subacute Endocarditis ACUTE BACTERIAL IE Usual Etiology

S. aureus B-Hemolytic Streptococci Pneumococci

Fever Course

High grade fever (39.4-40oC) Rapid Acute / decompensated heart failure common Hematogenously seeds extracardiac sites Poor (if untreated)


SUBACUTE BACTERIAL IE Streptococcus viridans Enterococci Coagulase-negative staphylococcus (prosthetic valve) HACEK Low grade fever (rarely >39.4oC) Indolent Rarely metastasizes Better prognosis

B. Non-Cardiac Manifestations MANIFESTATION DESCRIPTION Janeway lesions  Nontender, slightly raised hemorrhages on the palms and soles (seen in endocarditis) Osler’s nodes  Tender, raised nodules on the pads of the fingers or toes (seen in endocarditis) Splinter  Small blood clots that run vertically under the nails hemorrhages Glomerulonephritis  Caused by immune complex deposition at the glomerular basement membrane  Minor emboli: splinter hemorrhages, Janeway lesions, conjunctival hemorrhages Embolic events  Major emboli: arterial emboli, intracranial hemorrhage, pulmonary infarct, mycotic aneurysm Mycotic aneurysms  Focal dilations in the artery wall that have been weakened by infection or septic emboli IV. MANAGEMENT ORGANISM

Streptococci (Penicillin-sensitive)

   

RECOMMENDED REGIMEN Penicillin G (2-3 mU IV q4h) for 4 weeks Ceftriaxone (2 g/d IV OD) for 4 weeks Vancomycin (15 mg/kg IV q12h) for 4 weeks Penicillin G (2-3 mU IV q4h) OR Ceftriaxone (2 g IV OD) for 2 weeks PLUS Gentamicin (3 mg/kg IV or IM OD) as a single dose or divided into equal doses q8h for 2 weeks


Streptococci (Penicillin-resistant)

Enterococci Staphylococci (Methicillin-sensitive) Staphylococci (Methicillin-resistant) HACEK organisms Culture Negative

 Penicillin G (4-5 mU IV q4h) OR Ceftriaxone (2 g IV OD) for 6 weeks PLUS Gentamicin (3 mg/kg IV or IM OD) as a single dose or divided into equal doses q8h for 2 weeks  Vancomycin (15 mg/kg IV q12h) for 4 weeks  Penicillin G (4-5 mU IV q4h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks  Ampicillin (2 g IV q4h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks  Vancomycin (15 mg/kg IV q12h) PLUS Gentamicin (1 mg/kg IV q8h) both for 4-6 weeks  Nafcillin OR Oxacillin (2 g IV q4h) for 4-6 weeks  Cefazolin (2 g IV q8h) for 4-6 weeks  Vancomycin (15 mg/kg IV q12h) for 4-6 weeks  Vancomycin (15 mg/kg IV q8-12h) for 4-6 weeks  Ceftriaxone (2 g/d IV OD) for 4 weeks  Ampicillin/sulbactam (3 g IV q6h) for 4 weeks  Ampicillin/sulbactam (3 g IV q6h) PLUS Gentamicin (1 mg/kg IV q8h) for 4-6 weeks

V. PROPHYLAXIS IN ADULTS WITH HIGH RISK CARDIAC LESIONS  Amoxicillin 2 g PO 1 hour before procedure (standard oral regimen)  Ampicillin 2 g IV or IM 1 hour before procedure (unable to take oral medication)  For Penicillin allergy: o Clarithromycin or azithromycin 500 mg PO 1 hour before procedure o Cephalexin 2 g PO 1 hour before procedure o Clindamycin 600 mg PO 1 hour before procedure o Cefazolin or Ceftriaxone 1 g IV or IM 30 minutes before procedure HIGH RISK CARDIAC LESIONS  Prosthetic valves  Completely repaired congenital defects during the 6 months after repair  Prior endocarditis  Incompletely repaired congenital defects  Unrepaired cyanotic congenital defects

HUMAN IMMUNODEFICIENCY VIRUS: AIDS AND RELATED DISORDERS I. ETIOPATHOGENESIS A. Etiologic Agent  Etiologic agent: Human Immunodeficiency Virus (HIV)  Four retroviruses known to cause human disease o Human T lymphotropic viruses (HTLV)-1 and HTLV-II: transforming retroviruses o Human immunodeficiency viruses, HIV-1 and HIV-2: cause cytopathic effects  HIV-1 is the most common cause of HIV disease throughout the world  Hallmark of HIV disease: profound immunodeficiency resulting primarily from a progressive quantitative and qualitative deficiency of helper T cells, occurring in a setting of polyclonal immune activation B. Transmission  Primarily by sexual contact: worldwide, heterosexual transmission is still the most common mode  Blood and blood products  Occupational transmission of HIV  Infected mothers to infants intrapartum, perinatally or via breast milk  No evidence that HIV is transmitted by casual contact or that the virus can be spread by insect, such as by a mosquito bite II. CLINICAL MANIFESTATIONS ACUTE HIV SYNDROME  Occurs 3-6 weeks after primary infection along with a burst of plasma viremia

ASYMPTOMATIC STAGE (CLINICAL LATENCY)  Median time: 10 years untreated patients)  Ongoing and progressive


 Symptoms can appear at any time  More severe and life-threatening complications of HIV infection


 Symptoms: fever, skin rash, pharyngitis, myalgia  Most patients recover spontaneously from this syndrome  Many have only a mildly depressed CD4+ T cell count that remains stable for a variable period before beginning its decline

disease with active virus replication  Rate of disease progression is directly correlated with HIV RNA levels

occur in patients with CD4+ T cell counts 2 weeks before exposure  Booster dose – 1 dose IM every 3 years for travelers Live attenuated (oral)  Enteric-coated capsules every other day for 1 week  Single dose annually

 Single dose  Booster dose between 612 months after primary course

 3 doses: 0, 1, 6 months


Varicella  Live attenuated vaccine: SC

Measles, Mumps, Rubella (MMR)  Live attenuated: SC

 Close contact with persons at high risk for severe disease (e.g., health personnel and family contacts of immunocompromised persons) or at high risk for exposure or transmission (e.g. teachers, day care staff)  Residents and staff of correctional institutions  Military personnel  Adolescents and adults living in households with children  Non-pregnant women of childbearing age  Measles and mumps component: college students, health care workers, travelers  Rubella component: non-pregnant women of childbearing age should be vaccinated

 2 doses: 0, 1-2 months  Single dose postexposure prophylaxis: within 72 hours of exposure

 2 doses: 0, 1 month


CHAPTER 7 ENDOCRINOLOGY I. Introduction to Endocrinology II. Common Conditions in Endocrinology 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

The Metabolic Syndrome Diabetes Mellitus Gestational Diabetes Mellitus Hyperglycemic Crises in Diabetes Diabetic Foot Ulcer Hypoglycemia Hyperthyroidism Thyroid Storm Goiter and Nodular Thyroid Disease Osteoporosis Multiple Endocrine Neoplasia Cushing’s Syndrome Mineralocorticoid Excess Pituitary Diseases




BMI = Weight in kg (height in m)2 IDEAL BODY WEIGHT (IBW)

IBW Males = 106 lbs + (6 lbs per inch over 5 feet) IBW Females = 100 lbs + (5 lbs per inch over 5 feet) *Divide by 2.2 to convert to kilograms


WHR = Waist circumference in cm Hip circumference in cm    

Waist circumference should be measured at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest Hip circumference should be measured around the widest portion of the buttocks Used as an indicator or measure of the health of a person, and the risk of developing serious health conditions Abdominal obesity: defined as a waist-hip ratio >0.90 for males and >0.85 for females

A1C APPROXIMATES THE FOLLOWING MEAN PLASMA GLUCOSE VALUES HBA1C APPROXIMATE PLASMA GLUCOSE VALUE 6% 7.0 mmol/L (126 mg/dL) 7% 8.6 mmol/L (154 mg/dL) 8% 10.2 mmol/L (183 mg/dL) 9% 11.8 mmol/L (212 mg/dL) 10% 13.4 mmol/L (240 mg/dL) 11% 14.9 mmol/L (269 mg/dL) 12% 16.5 mmol/L (298 mg/dL)



COMMON CONDITIONS IN ENDOCRINOLOGY THE METABOLIC SYNDROME I. ETIOLOGY  Metabolic abnormalities that confer an increased risk of cardiovascular disease and diabetes mellitus  Insulin resistance: most accepted an unifying hypothesis in metabolic syndrome  Hypertriglycerides is an excellent marker of insulin resistance  Other associated conditions: non-alcoholic fatty liver, hyperuricemia, polycystic ovarian syndrome and obstructive sleep apnea II. DIAGNOSIS A. BMI Classification CLASSIFICATION OF BMI (kg/m2) Underweight Normal Overweight Obese I Obese II Obese III

WHO INTERNATIONAL CLASSIFICATION < 18.5 18.5 – 24.99 > 25 > 30 > 35 > 40

CLASSIFICATION IN ASIANS < 18.5 18.5 – 22.9 23 – 24.9 25 – 29.9 > 30

B. NCEP: ATP III 2001 Criteria for the Metabolic Syndrome (requires 3 or more of the following) Central Obesity  Waist circumference >102 cm (M) or >88cm (F) Hypertriglyceridemia  TG > 150 mg/dL or use of specific medication Low HDL Cholesterol  85 diastolic or use of specific medication Fasting Glucose  > 100 mg/dL or specific medication or preciously diagnosed T2DM C. Harmonizing Definition for the Metabolic Syndrome (requires 3 or more of the following)  > 90 cm (M) or > 80 cm (F) in South Asian, Chinese, and Ethnic South and Central American Waist circumference  > 85 cm (M) or > 90 cm (F) in Japanese  > 94 cm (M) or > 80 cm (F) in Europe, Sub-Saharan African, Eastern and Middle Eastern Hypertriglyceridemia  TG > 150mg/dL or use of specific medication Low HDL Cholesterol  < 40 mg/dL (M) or < 50 mg/dL (F) or use of specific medication Hypertension  BP > 130 systolic or > 85 diastolic or use of specific medication Fasting Glucose  > 100 mg/dL or specific medication or previously diagnosed T2DM TG: Triglycerides M: Males; F: Females

III. MANAGEMENT OF OBESITY TREATMENT 25 – 26.9 Diet & Exercise + if with comorbids Pharmacotherapy Surgery    


27 – 29.9 + if with comorbids + if with comorbids -

BMI CATEGORY (kg/m2) 30 – 34.9 +

35 – 39.9 +

> 40 +





+ if with comorbids


Dietary therapy: primary focus is reduction in overall calorie consumption Diet and exercise: combination of dietary modification and exercise is the most effective behavioral approach Pharmacotherapy: appetite suppressants (e.g., phentermine) and gastrointestinal fat blockers (e.g., orlistat) Surgery: classified into three (restrictive, restrictive-malabsorptive, and malabsorptive)


DIABETES MELLITUS I. ETIOPATHOGENESIS  Group of metabolic disorders that share the common phenotype of hyperglycemia  DM is defined as the level of glycemia at which diabetes-specific combinations occur A. Classification of Diabetes (based on the pathogenic process that leads to hyperglycemia)  Type 1 DM: result of interactions of genetic, environmental and immunologic factors that ultimately lead to destruction of pancreatic beta cells and insulin deficiency  Type 2 DM: heterogenous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion and excessive hepatice glucose production B. Risk Factors for Type 2 DM  Physical inactivity  Family history of diabetes (e.g., parent or sibling with T2DM)  Obesity (BMI > 25 kg/m2 or ethnically relevant definition for overweight)  High-risk ethnicity (e.g. African American, Latino, Native American, Asian American, Pacific Islander)  GDM or delivery of a baby > 9 lbs (4 kg)  History of cardiovascular disease or hypertension (> 140/90 mmHg)  HDL cholesterol < 35mg/dL (0.90 mmol/L) and/or triglycerides >250 mg/dL (2.82 mmol/L)  HbA1C 5.7-6.4%, IGT or IFG on previous testing  Conditions with insulin resistance (e.g. acanthrosis nigricans, polycystic ovary syndrome) C. Classification of Glucose Tolerance GLUCOSE FASTING PLASMA GLUCOSE TOLERANCE (FPG) Normal < 10 mg/dL (5.6 mmol/L) Impaired Glucose 100-125 mg/dL (5.6-6.9 mmol/L) Homeostasis Impaired Fasting Glucose (IFG) Diabetes Mellitus > 126 mg/dL (7.0 mmol/L)

GLUCOSE AFTER ORAL GLUCOSE CHALLENGE < 140 mg/dL (7.8 mmol/L) 140-199 mg/dL (7.8-11 mmol/L) Impaired Glucose Tolerance (IGT) > 200 mg/dL (11.1 mmol/L)

HbA1C < 5.7% 5.7-6.4% > 6.5%

II. CLINICAL FEATURES OF DIABETES  Classic symptoms: polyuria, polydipsia, polyphagia, nocturia, weight loss  Others: fatigue, weakness, blurred vision, frequent superficial infections and poor wound healing A. Acute Complications of DM  Diabetic Acidosis  Hypoglycemic hyperosmolar state B. Chronic Complications of DM MICROVASCULAR Eye disease  Retinopathy (nonproliferative/ proliferative)  Macular edema Neuropathy  Sensory and motor (mono-/ polyneuropathy)  Autonomic


Coronary artery disease Peripheral arterial disease Cerebrovascular disease

OTHERS Gastrointestinal (gastroparesis, diarrhea) Genitourinary (uropathy, sexual dysfunction Dermatologic Cataracts and glaucoma Periodontal disease Hearing loss Increased risk for infection Cheiroarthropathy (thick skin + reduced joint mobility)

Nephropathy (albuminuria, declining renal function)


III. DIAGNOSIS OF DIABETES MELLITUS A. Criteria for the Diagnosis of DM Either of the following:  Hemoglobin A1C > 6.5%, or  FPG > 126 mg/dL (7.0 mmol/L), or  2-hour plasma glucose > 200 mg/dL (11.1 mmol/L) during 75 g OGTT, or  Symptoms of DM + RBS > 200 mg/dL (11.1 mmol/L)

Note:  Current criteria emphasize the HbA1C or the FPG as the most reliable and convenient tests  Perform HbA1C with an assay-standardized method  “Fasting”: no caloric intake for at least 8 hours  “Random”: without regard to time since last meal  In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on a different day

FPG: Fasting Plasma Glucose OGTT: Oral Glucose Tolerance Test (performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water)

B. Screening for DM  Begin at age 45 years every 3 years  Earlier age if they are overweight (BMI > 23) + one additional risk factor for DM (see above)  May use A1C FPG, or 2-hour plasma glucose after 75 g OGTT for screening IV. MANAGEMENT OF DIABETES A. Insulin Therapy  Common side effects are hypoglycemia and weight gain  Adjust doses in renal insufficiency INSULIN PREPARATION ONSET OF ACTION Rapid and Short Acting Insulin Lispro (Rapid) < 15 mins Aspart (Rapid) Glulisin (Rapid) Regular (Short) 30-60 mins Intermediate and Long Acting Insulin Isophane/NPH (Intermediate) 2-4 hours Glargine (Long) Detemir (Long) 1-4 hours



30-90 mins

2-4 hours

2-3 hours

3-6 hours

4-10 hours Minimal peak activity

10-16 hours Up t0 24 hours

1. Three Major Components of Exogenous Insulin Therapy  Required to regulate metabolic processes even in the absence of meals Basal Insulin  Usual “basal insulin”: given as intermediate or long-acting insulin  Intermediate-acting insulin usually given in portions of 2/3 in AM and 1/3 in PM  Required to cover glycemic excursions following a meal Bolus Insulin  Usual “bolus insulin”: given as short or rapid-acting insulin  Rapid-acting insulin given within 15-20 minutes or immediately before meals  Short-acting insulin given within 30-45 minutes before meals Correctional Insulin  Supplemental doses of short or rapid-acting insulin given to correct elevations in blood glucose that occur despite the use of basal and bolus insulin 2. Initiating Insulin Therapy in T1DM  Calculate total insulin requirement: usually 0.5-1 units/kg per day  50% of computed value given as basal insulin 3. Initiating Insulin Therapy in T2DM Basal Insulin  Calculate dose at 0.2 units/kg/day for insulin-naïve patients Bolus Insulin  Initiated if unable to achieve target A1C with basal insulin alone  Start with 4 units before each meal OR calculate each dose at 0.1 units/kg  Calculate dose at 0.3 to 0.5 units/kg/day: Basal-bolus Insulin o 50% of dose will be given as basal insulin  NPH: 2/3 pre-breakfast, 1/3 pre-dinner


Sample Order

 Glargine or Detemir: give at bedtime o 50% of dose will be given as bolus insulin in equal divided doses pre-meals Example:  Intermediate acting insulin: 20-0-10 (this means, 20 units given pre-breakfast + 10 units given pre-supper)  Regular acting insulin: 4-4-4 (this means, 4 units given pre-breakfast, 4 units given pre-lunch, and 4 units given pre-supper)

B. Common Hypoglycemic Agents (OHAs) DRUG CLASS SUBTYPES

Sulfonylureas Insulin Secretagogues Non-sulfonylureas


Gliclazide Glibenclamide Glimepride Glipizide Repaglinide Nateglinide




Rosiglitazone Pioglitazone

Alpha-glucosidase Inhibitors Lipase Inhibitors

Acarbose Miglitol Orlistat Sitagliptin Saxagliptin Linagliptin Vildagliptin Exenatide Liraglutide

Insulin Sensitizers

Intestinal Absorption Inhibitors

Increases insulin secretion

Decreases hepatic glucose production and improves peripheral glucose utilization Decreases insulin resistance, increases glucose utilization

DPP-IV Inhibitors IncretinRelated Drugs GLP-1 Agonists (Parenteral)




Hypoglycemia Weight gain

 

Weight loss Lactic acidosis

      

Edema Weight gain Osteoporosis Anemia Weight loss Diarrhea Flatulence

Inhibits intestinal absorption of sugars

Prolongs endogenous GLP-1 action

 

Headache Nasopharyngitis

Increases, urinary glucose excretion Inhibits subtype 2 Na+glucose transport protein which is responsible for at least 90% of glucose reabsorption in the kidney Slows gastric emptying Decreases glucagon

 

Glucosuria Urinary tract & vaginal infections Dehydration Hyperkalemia (limited clinical experience) Nausea hypoglycemia

Na+ -Glucose Co-Transporter-2 Inhibitors

Dapagliflozin Canagliflozin Empagliflozin

Amylin Agonists (Parenteral)


 

   


C. Drugs and their Primary Areas of Control  goals of treatment based on HbA1C o If HbA1C is 9% Control FPG first MONOTHERAPY COMBINATION THERAPY Sulfonylureas Metformin Thiazoldinediones Meglitinides GLP-1 agonists Acarbose DPP-IV inhibitors



Sulfonylurea + Metformin Sulfonylurea + Thiazolidinedione Sulfonylurea + GLP-1 agonist Metformin + Meglitinide

INSULIN Lispro Aspart Regular NPH Glargine Detemir





FPG: Fasting Plasma Glucose PPG: Postprandial Glucose

D. Goals of Treatment INDEX Glycemic Control HbA1C (primary goal) Preprandial capillary plasma glucose Peak postprandial capillary plasma glucose* Blood Pressure ** Lipids** Low-density lipoprotein (LDL) High-density lipoprotein (HDL) Triglycerides

GOAL    

< 7.0% 80-130 mg/dL (4.4 – 7.2 mmol/L) < 180 mg/dL (10.0 mmol/L) < 140/90 mmHg (130/80 for younger patients)

 

< 100 mg/dL (2.6 mmol/L) >40 mg/dL (1 mmol/L) [M] or > 50 mg/dL (1.3 mmol/L) [F} < 150 mg/dL (1.7 mmol/L)

*Peak postprandial capillary plasma glucose: 1-2 hours after beginning a meal **see JNC-8 and Dyslipidemia Guidelines in Cardiology Chapter (values indicated are from the ADA)

E. Self-Monitoring of Blood Glucose (SMBG): For patients on multiple-dose insulin or insulin pump  Prior to meals and snacks, occasionally postprandially, and at bedtime  Prior to exercise or critical tasks such as driving  When they suspect low blood glucose  After treating low blood glucose until they are normoglycemic F. Monitoring Response DRUG Sulfonylureas


1-2 weeks Meglitinides Metformin

2-3 weeks


2-4 weeks


1-2 months

DPP-IV Inhibitors

2 weeks

             

WHEN TO MONITOR RESPONSE? FPG at 2 weeks HbA1C at 3 months FPG at 2 weeks HbA1C at 3 months PPG at initiation FPG at 2 weeks HbA1C at 3 months HbA1C at 3 months PPG at initiation FPG at 4 weeks HbA1C at 3-6 months FPG at 2 weeks HbA1C at 3 months PPG at initiation


V. ANTICIPATORY CARE A. Recommended Annual Laboratories LABORATORY HbA1C testing Screening for Diabetic Neuropathy Lipid profile & Serum Creatinine

FREQUENCY 2-4 times / year Annual Annual

B. Cornerstones of Anticipatore Care   Lifestyle Changes


    

Antiplatelet Agents

Diabetic Kidney Disease

 




  

Moderate weight loss of 7% of body weight 150 min/week moderate intensity aerobic exercise, spread over at least 3 days/week, with no more than 2 consecutive days without exercise Dietary fiber intake of 14 g of fiber/1,000 kcal; saturated fat intake 50 years or women >60 years with at least one major risk factor Recommended daily protein allowance of 0.8 g/kg/day Screening (comprehensive eye examination by an ophthalmologist or optometrist) o Type 1 diabetes: within 5 years after diagnosis o Type 2 diabetes: shortly after diagnosis Influenza vaccine to all diabetics > 6 months of age Pneumococcal vaccine if > 2 years old, revaccination if >64 years old Hepatitis B vaccine in unvaccinated adult diabetic 19-59 years old

C. Approved Drugs for Management of Pre-diabetes (IGT, IFG, HbA1C 5.7-6.4%)  Metformin (strongest evidence)  Acarbose  Thiazolidinediones

GESTATIONAL DIABETES MELLITUS (GDM) I. DEFINITIONS  Overt DM: pregnant woman who meets the criteria for diagnosis of DM  Pre-Gestational DM: diagnosed in a woman even before pregnancy  GDM: diagnosed in the 2nd and 3rd trimester of pregnancy that is not clearly overt DM II. DIAGNOSIS (ONE-STEP STRATEGY)  Screen at first prenatal visit based on the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria using the 75 g OGTT Any of the following:  FPG: > 92 mg/dL (5.1 mmol/L)  1 hr PPG: > 180 mg/dL (10.0 mmol/L)  2 hr PPG: > 153 mg/dL (8.5 mmol/L) III. MONITORING  Do SMBG before and 1 hr or 2 hrs after the start of each meal/after the first bite  Glycemic targets in pregnancy GDM PREEXISTING TYPE 1 AND TYPE 2 DM  FPG < 95 mg/dL (5.3 mmol/L)  FPG 60-99 mg/dL (3.3-5.4 mmol/L)  1-hr PPG < 140 mg/dL (7.8 mmol/L)  PPG 100-129 mg/dL (5.4-7.1 mmol/L)  2-hr PPG < 120 mg/dL (6.7 mmol/L)  HbA1C 29.9) 12

TOTAL WEIGHT GAIN 300 mg/dL 2. Hyperosmotic Hyperglycemic State (HHS)  Greater degree of dehydration and higher endogenous insulin secretion compared with DKA  Primarily seen in individuals in T2DM  Insulin levels inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to prevent lipolysis and ketogenesis


II. CLINICAL MANIFESTATIONS A. Diagnostic Criteria for DKA and HHS

Plasma Glucose (mg/dL) Arterial pH Serum bicarbonate (mEq/L) Urine ketones Serum ketones Effective serum osmolality (mOsm/kg) Anion gap Alteration in Sensorium

MILD >250 7.25-7.30 15-18 Positive Positive Variable >10 Alert

DKA MODERATE >250 7.00-7.24 10 to 12 Alert/drowsy

B. Differentiating Features of DKA and HHS INDEX DKA CLINICAL FEATURES Symptoms Nausea, vomiting, thirst, polyuria, abdominal pain, dyspnea Tachycardia, dehydration, tachypnea, Signs Kussmaul respirations, abdominal tenderness, decreased sensorium Development of manifestations LABORATORY VALUES Glucose mmol/L (mg/dL) Na+ (mEq/L) K+ Mg2+ ClPhosphate Creatinine Osmolality (mOsm/mL) Plasma ketones Serum bicarbonate (mEq/L) Arterial pH Arterial PCO2 (mmHg) Anion Gap (Na- [Cl + HCO3])

HHS SEVERE >250 600 >7.30 >15 Small Small >320 Variable Stupor/coma


Over 24 hours

Polyuria, weight loss, diminished oral intake, mental confusion, lethargy, coma Profound dehydration, hypotension, tachycardia, altered mental status (No nausea, vomiting, abdominal pain or Kussmaul respiration unlike DKA) Several weeks

13.9 – 33.3 (250-600) 125-135 Normal to increased Normal Normal Decreased Slightly increased 300-320 ++++ < 15 mEq/L

33.3 – 66.6 (600-1200) 135-145 Normal Normal Normal Normal Moderately increased 330-380 +/Normal to slightly decreased

6.8 – 7.3 20-30 High

> 7.3 Normal Normal to slightly high

III. MANAGEMENT A. General Management  Admit to ICU  Measure capillary blood glucose (CBG) every 1-2 hours  Monitor BP, pulse, respirations, mental status and fluid I & O every 1-4 hours  Assess serum electrolytes, ABG and renal function  15-20 mL/kg/hr or 1-1.5 L of pNSS during the first hour (unless with risk of congestion)  Once CBG is ~200-250 mg/dL, shift fluids to D5-IVF (glucose-containing) Fluid Therapy  IVF replacement should correct estimated deficits within the first 34 hours  In renal/cardiac patients, monitor serum osmolality and cardiac, renal and mental status to avoid iatrogenic overload  Regular insulin preferably by IV route (short half-life & easy titration): mainstay of therapy  Initial IV bolus (0.1 unit/kg) is given, then infusion started at 0.1 units/kg/hr (see algorithm) Insulin Therapy  If CBG does not decrease ~50-75 mg/dL/hr, increase insulin infusion rate (two to threefold) hourly until with a steady glucose decline  When CBG ~200 mg/dL in DKA or 300 mg/dL in HHS, may decrease insulin infusion rate



  

Bicarbonate 

to 0.02-0.05 units/kg/hr to maintain CBG 150-200 mg/dL in DKA or 250-300 mg/dL in HHS Despite depletion of total body potassium, mild-moderate hyperkalemia is common Insulin therapy, correction of acidosis & volume expansion decrease serum K + If pH 7.0 Repeat every 2 hours until pH reaches >7.0


Complete initial evaluation. Check capillary glucose and serum/urine ketones to confirm hyperglycemia and ketonemia/ketonuria. Obtain blood for metabolic profile. Start IV fluids: 1.0 L of 0.9% NaCl per hour1

IV Fluids

Bicarbonate pH > 6.9

Insulin: Regular IV Route (DKA and HHS)

pH < 6.9

Determine hydration status Cardiogenic Shock

Severe Hypovolemia Mild dehydration

Hemodynamic monitoring/ pressors

Administer 0.9% Nacl (1.0L/hr)

Elevated corrected serum Na+ Serum Na+ high

Serum Na+ normal

0.45% NaCl (250-500 ml/hr) depending on hydration state

Serum Na+ low

0.9% NaCl (250-500 ml/hr) depending on hydration state

When serum glucose reaches 200 mg/dl (DKA) or 300 mg/dl (HHS), change to 5% dextrose with 0.45% NaCl at 150-250 ml/hr

No HCO3-

100 mmol in 400 ml H2O + 20mEq KCL, infuse for 2 hours


IV Route (DKA and HHS)

Establish adequate renal function (urine output – 50 ml/hr)

0.1 U/kg/B. Wt. as IV bolus

0.1 U/kg/hr IV continuous insulin infusion

Repeat every 2 hours until pH > 7. Monitor serum K+ every 2 hours

0.14 U/kg Bwt/hr as IV continuous insul infusion

Hold insulin and give 20 – 30 mEq/hr Until K+ >3.3 mEq/L

If serum glucose does not fall by at least 10% in first hour, give 0.14 U/kg as IV bolus, then continue previous Rx

DKA When serum glucose reacges 200 mg/dL, reduce regular insulin infusion to 0.02-0.05 U/kg/hr IV, or give rapid-acting insulin at 0.1 U/kg SC every 2 hours. Keep serum glucose between 150 and 200 mg/dl until resolution of DKA.

K+ 5.2 mEq/L

Do not give K+, but check serum K+ every 2 hours

K+ = 3.3 – 5.2 mEq/L

Give 20 – 30 mEq K+ in each liter of IV fluid to keep serum K+ between 4-5 mEq/L

Check electrolytes, BUN, venous pH, creatinine and glucose every 2-4 hrs until stable. After resolution of DKA or HHS and when patient is able to eat, initiate SC multidose insulin regime. To transfer from IV to SC, continue IV insulin infusion for 1-2 hrs after SC insulin begun to ensure adequate plasma insulin levels. In insulin naïve patients, start at 0.5 U/kg to 0.8 U/kg body weight per day and adjust insulin as needed. Look for precipitating cause(s).


B. Transition to Subcutaneous (SQ) insulin  Overlap 1-2 hours between IV and SQ insulin to prevent recurrence of hyperglycemia or ketoacidosis  If the patient remains on NPO, continue IV insulin  Patients with known DM may be given insulin at the dose they were receiving before the onset of DKA so long as it was controlling glucose properly  For insulin-naïve patients, start insulin regimen at 0.5-0.8 units/kg/day C. Criteria for Resolution DKA Plasma glucose 15 mEq/L  Venous pH >7.3  Calculated anion gap < 12 mEq/L

 

HHS Normal serum osmolality Improvement of normal mental status

IV. COMPLICATIONS A. Hypoglycemia and Hypokalemia  Due to overzealous treatment of DKA with insulin and bicarbonate B. Hyperchloremic Non-Anion Gap Acidosis  Usually seen during the recovery phase of DKA  Caused by loss of ketoanions plus excess infusion of chloride-containing fluids during treatment C. Cerebral Edema  Occurs in ~0.3-1% of DKA in children but rare in adults  Associated with 20-40% mortality rate  Symptoms: headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary changes, papilledema, bradycardia, elevation in BP and respiratory arrest  Treated with mannitol and mechanical ventilation

DIABETIC FOOT ULCER I. ETIOPATHOGENESIS  Diabetics are prone to foot ulcers  Development is attributed to: neuropathy, ischemia, infection and immune impairment  Neuropathy: most common underlying etiology of foot ulceration II. CLASSIFICATION OF DIABETIC FOOT ULCERS A. Wagner Classification System  Assesses ulcer depth and the presence of osteomyelitis or gangrene o Grade 0: pre- or post-ulcerative lesion, completely epithelialized o Grade 1: partial / full thickness ulcer; superficial wound o Grade 2: penetrates the tendon or capsule o Grade 3: deep with osteitis o Grade 4: partial foot gangrene o Grade 5: whole foot gangrene B. University of Texas System  Assesses ulcer depth, presence of wound infection, and presence of signs of lower-extremity ischemia  Within each wound grade, there are four stages  Example: A superficial wound that is ischemic but not infected is classified as Grade 1, Stage C DEPTH OF ULCER PRESENCE OF INFECTION / ISCHEMIA  Grade 0: pre- or post-ulcerative lesion, epithelialized  Stage A: (-) infection, (-) ischemia  Grade 1: superficial wound  Stage B: (+) infection, (-) ischemia  Grade 2: wound penetrates tendon or capsule  Stage C: (-) infection, (+) ischemia


 Grade 3: wound penetrates bone and joint III. DIFFERENTIALS FOR A FOOT ULCER FOOT ULCER USUAL ETIOLOGY  Diabetic neuropathy (“DM Neuropathic Ulcer foot”)

Arterial (Ischemic) Ulcer

Venous Ulcer

 Peripheral arterial occlusive disease (PAOD)

 Chronic venous insufficiency (CVI)

 Stage D: (+) infection, (+) ischemia

DESCRIPTION  Located at the sites of trauma, such as areas of callus formation, bony prominence or parts of foot exposed to mild chronic trauma  Small, annular, pale, tender, circumscribed and dessicated  Located on distal areas of limbs (e.g., toes, heels, fingertips)  May progress to tissue necrosis & gangrene  May co-exist in diabetic patients with PAOD  Large, irregular borders, erythematous & moist (shiny appearance)  Located near the medial or lateral malleolus  Chronic venous edema may impart hemosiderin deposition in the skin, giving rise to a “brawny appearance”

IV. MANAGEMENT A. Screening & Surveillance  Screen for distal polyneuropathy at diagnosis and at least annually thereafter  Annual comprehensive foot examination o Inspection o Assessment of foot pulses and ankle brachial index (ABI) o Tests for loss of protective sensation: 10-g monofilament plus either: vibration using 128-Hz tuning fork, pinprick sensation, ankle reflexes, and vibration perception threshold B. General Management  Medications for relief of symptoms from polyneuropathy or autonomic neuropathy are recommended  General foot self-care education  Use multi-disciplinary approach: o Refer patients to foot care specialists for ongoing preventive care and surveillance o Refer patients with significant claudication or positive ABI for further vascular assessment

HYPOGLYCEMIA I. ETIOPATHOGENESIS  Defined as glucose levels 140 25 2. Congestive Heart Failure / Atrial Fibrillation Absent 0 Mild (pedal edema) 5 Moderate (bibasilar rales) 10 Severe (pulmonary edema) Atrial Fibrillation 3. Precipitant History

15 10


Moderate (diarrhea, vomiting, abdominal pain) Severe (unexplained jaundice)


Highly suggestive of storm

IV. MANAGEMENT  Goals of Management o Stop synthesis of new thyroid hormones o Halt release of preformed thyroid hormones o Prevent conversion of T4 to T3 o Control adrenergic symptoms associated with thyrotoxicosis o Control systemic decompensation o Treat underlying cause MECHANISM DRUG DOSE ACTION  Inhibits thyroid peroxidase (TPO) Inhibition of 600-1000 mg LD and  Inhibits peripheral conversion of T4 to T3 on new PTU 200-300 mg q6h high doses hormone PO/NGT/PR  Decreases circulating TSI production  Restores normal suppressor cell activity Methimazole 20-25 mg PO q6h  Inhibits thyroid peroxidase (TPO) Supersaturated 5 drops q6h 1 hour after Inhibit PTU (Wolff-Chaikoff Solution of preformed Effect) Potassium Iodide  Blocks thyroid hormone release hormone (SSKI)  Decrease fractional turnover of thyroid iodine release Lugol’s Solution 4-8 drops PO q6-8h and T4 secretion rate Sodium ipodate 1-3 g PO QID Iopanoic acid 1 g PO q8h 60-80 mg PO q4g or 80 Reduces sympathetic overdrive Control of Propranolol 120 mg q6h  High doses also decrease peripheral adrenergic conversion of T4 to T3 symptoms Atenolol 50-200 mg PO QID  Cardioselective Metoprolol 100-200 mg (may be used in COPD and asthma) Esmolol 50-100 mcg/kg/min Acetaminophen 325-650 mg PO q4-6h Supportive Hydrocortisone 100 mg IV q8  Decreases peripheral conversion of T4 management  Addresses relative adrenal insufficiency Glucose 5-10% solution  Mimics iodine Lithium 300 mg PO q8h  Inhibits coupling of iodotyrosinases and Alternatives peripheral conversion of T4 Potassium 1 g PO QID perchlorate cholestyramine 4 g PO QID  Hastens removal of T4 and T4 from serum

HYPOTHYROIDISM I. ETIOPATHOGENESIS  Results from undersecretion of thyroid hormone  Iodine deficiency remains the most common cause worldwide  Most common causes in areas of iodine insufficiency: autoimmune disease (Hashimoto’s thyroiditis) & iatrogenic  Secondary causes include pituitary and hypothalamic disease


II. CLINICAL MANIFESTATIONS SYMPTOMS Tiredness, weakness Dry skin Cold intolerance Hair loss Difficulty concentrating and poor memory Constipation Weight gain with poor appetite Dyspnea & hoarse voice Menorrhagia (later oligomenorrhagia or amenorrhea) Paresthesia Impaired hearing

SIGNS Dry coarse skin Cool peripheral extremities Puffy face, hands and feet (myxedema) Diffuse alopecia Bradycardia Peripheral edema Delayed tendon reflex relaxation Carpal tunnel syndrome Serous cavity effusions

Arranged in Decreasing Order of Frequency

III. COMMON DIAGNOSTICS A. Common Diagnostics Used: DIAGNOSTICS Sensitive TSH analysis Free T4 Thyroid autoantibodies Thyroid scan ultrasound

     

COMMENTS/EXPECTED FINDINGS Elevated in primary hypothyroidism May be normal in secondary hypothyroidism (pituitary disease) Low in primary hypothyroidism May be normal in mild hypothyroidism May be noted in autoimmune etiologies To determine the specific cause of hypothyroidism

B. Interpretation of Thyroid Function Test Results RESULTS DIFFERENTIALS TSH FT4 High Normal  Mild hypothyroidism High Low  Primary hypothyroidism  Autoimmune hypothyroidism (if thyroid autoantibodies are positive) Normal Low  Drug effects, sick euthyroid syndrome, pituitary disease IV. MANAGEMENT: LEVOTHYROXINE (LT4) A. Dosage  Start usually with 25-50 mcg/day (1.6 mcg/kg/day)  Use lower dosages of 12.5-25 mcg for patients >60 y/o and those with cardiac disease B. Duration  Symptoms improve in weeks; lifelong treatment is necessary  Increase dose by 25-50mcg every 4 weeks until patient is clinically and biochemically euthyroid C. Monitoring  Monitor plasma TSH q3-4 months (maintain in normal range)  For secondary hypothyroidism, monitor serum T4 and other pituitary hormones and give steroid replacement prior to LT4

GOITER AND NODULAR THYROID DISEASE I. ETIOPATHOGENESIS  Goiter is defined as an enlarge thyroid gland  Causes include biosynthetic defects, iodine deficiency, autoimmune disease and nodular diseases II. CLASSIFICATION A. Diffuse Non-Toxic (Simple or Colloid) Goiter


   

Diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism Thyroid function is preserved and most patients are asymptomatic Pemberton’s sign: symptoms of faintness with facial congestion and external jugular venous obstruction when arms are raised above the head Levothyroxine can be started to suppress the TSH into the low-normal, but detectable, range

B. Non-Toxic MNG  Most are asymptomatic  Thyroid architecture is distorted and multiple nodules can be appreciated C. Toxic MNG  Presence of functional autonomy in contrast to non-toxic MNG  TSH is low, T4 level is normal or minimally increased, and T3 is often elevated to a greater degree than T4  Antithyroid drugs often given with beta-blockers can normalize thyroid function III. APPROACH TO A THYROID NODULE

Thyroid Scan

“Hot” Nodule

Ablate, resect or medically manage Surgery if further growth or suspicious cytology


Solitary or Suspicious Nodule

“Cold” Nodule or Intermediate

Non Diagnostic (17%)


Monitor by US

“Hot” Nodule

Benign (69%)

Normal TSH

US Guided FNA

Released by inadequate


Suspicious or Follicular (10%) Malignant (4%)

Consider Thyroid Scan “Cold” or Intermediate



OSTEOPOROSIS I. ETIOPATHOGENESIS AND DIAGNOSIS  A reduction in the strength of bone that leads to an increased fracture risk  Diagnosed based on WHO classification criteria for bone mass using dual-energy x-ray absorptiometry (DXA) as gold standard  Presence of vertebral fractures on either radiograph or VFA examination confirms clinical diagnosis of osteoporosis  Recommended DXA sites: femoral neck or total femur and/or lumbar spine (distal third of radius if cannot evaluate spine/hips)  Peripheral BMD technologies (quantitative UTZ, CT scan, single x-ray absorptiometry) done in sites like the calcaneus, wrist and metatarsals and bone turnover markers should not be used in the diagnosis of osteoporosis (but can be used in fracture risk assessment and assessing adherence to and effectiveness of therapy) BONE MINERAL DENSITY (T-Score) Normal > -1 SD Osteopenia / Low bone mass Between -1 and -2.5 SD Osteoporosis < -2.5 SD Severe osteoporosis < -2.5 SD and > 1 fragility fracture/s II. SCREENING A. Osteoporosis Screening Tool for Asian (OSTA)  Used to identify an individual’s risk for osteoporosis in areas where DXA is not widely available Weight (kg) (lbs)

40-44 88-98

45-49 99-109

50-54 110-119

55-59 120-130

60-64 131-141

65-69 142-152

Age 40-44 45-49 50-54 55-59

75-79 165-174

80-84 175-185

85-89 186-196

90-94 197-208


60-64 65-69 70-74 75-79 80-84 85-89

70-74 153-164


90-94 95-99 A simple tool to identify Asian women at increased risk of osteoporosis.

B. Fracture Risk Assessment Tool (FRAX)  Used to assess fracture probability in all postmenopausal women with at least one WHO risk factor, prior to undergoing central DXA: o Low BMI o Previous fragility fracture o Parental history of hip fracture o Glucocorticoid treatment o Current smoking o Alcohol intake (at least 3 units/day) o Rheumatoid arthritis o Other secondary causes of osteoporosis (e.g., CKD, liver disease, malabsorption, IBD, hypogonadism, hyperparathyroidism, Cushing’s disease, COPD, androgen deprivation therapy, malignancies) C. Indications for Bone Density Testing (consider BMD testing):  Women > 65 years and men > 70 years (regardless of risk factors)  Younger postmenopausal women, women in menopausal transition and men 50-69 years with risk factors for fracture  Adults who have a fracture after age 50


Adults with a condition associated with low bone mass or bone loss (e.g., RA, on steroids > 3 months)

III. MANAGEMENT OF OSTEOPOROSIS A. Indications to Treat IF WITH BMD MEASUREMENT, TREAT IF:  Vertebral compression fracture evident on VFA or confirmed through radiograph (clinical osteoporosis)  BMD T-score of < -2.5 SD

IF WITHOUT BMD MEASUREMENT, TREAT IF:  Belongs to high-risk category based on OSTA tool where central BMD cannot be done or not available  10-year probability of hip fracture >3% or any major osteoporosis related fracture >20% based on FRAX estimates

B. Pharmacologic Therapies  Biphosphonates  Hormonal replacement therapy  Selective estrogen receptor modulators (SERM)  Strontium ranelate  Parathyroid hormone or its analog (teriparatide)  Calcitonin  Tibolone  RANKL inhibitor (denosumab)  Vitamin D or its analog, in combination with calcium, is used as mandatory adjunct IV. PREVENTION Calcium Exercise Lifestyle

    

Calcium supplementation at least 750-800 mg daily for a minimum of 2 years to prevent bone loss Vitamin D3 10-20 mcg to be given with 1000 mg calcium, especially for those with limited sun exposure Supervised high intensity resistance exercise (8-12 repetitions at least 2-3 days/week) Moderate levels of walking (24 METs/week or 8 h/week of walking at an average pace) Smoking cessation and limiting alcohol consumption

MULTIPLE ENDOCRINE NEOPLASIA (MEN) MEN 1  Parathyroid hyperplasia / adenoma  Pancreatic islet cell hyperplasia / adenoma / carcinoma  Pituitary hyperplasia / adenoma

   

 Less common manifestations: foregut carcinoid, pheochromocytoma, subcutaneous or visceral lipomas

 

MEN 2 MEN 2A Medullary thyroid carcinoma Pheochromocytoma Parathyroid hyperplasia/adenoma MEN 2A + cutaneous lichen amyloidosis MEN 2A + Hirschprung’s disease Familial medullary thyroid carcinoma

MEN 2B  Medullary thyroid carcinoma  Pheochromocytoma  Mucosal and gastrointestinal neuromas  Marfanoid features

CUSHING’S SYNDROME I. ETIOPATHOGENESIS  Constellation of clinical features that result from chronic exposure to excess glucocorticoids of any etiology  Iatrogenic use of glucocorticoids (for immunosuppression or treatment of inflammatory disorders) is the most common cause  Cushing’s disease refers specifically to Cushing’s syndrome caused by a pituitary corticotrope adenoma II. CLASSIFICATION A. ACTH-Dependent  Means that Cushing’s syndrome is due to excess ACTH


Possible sources of ACTH excess: o Pituitary corticotrope adenoma (Cushing’s disease) o Ectopic secretion of ACTH by nonpituitary tumor (paraneoplastic syndrome)

B. ACTH-Independent  Means that Cushing’s syndrome is not due to excess ACTH  Majority of patients with ACTH-independent cortisol excess harbor a cortisol-producing adrenal adenoma  Other causes include adrenocortical carcinoma and nodular adrenal hyperplasia III. CLINICAL FEATURES BODY COMPARTMENT/SYSTEM Body fat


Bone Muscle

  

Cardiovascular System Metabolism Reproductive System

  

Central Nervous System

Blood and immune System

SIGNS AND SYMPTOMS Weight gain, central obesity, rounded face, fat pad on back of neck (“buffalo hump”) Facial plethora, thin and brittle skin, easy bruising, broad and purple stretch marks, acne, hirsutism Osteopenia, osteoporosis (vertebral fractures) Decreased linear growth in children Weakness, proximal myopathy (prominent atrophy of gluteal and upper leg muscles) Hypertension, edema, atherosclerosis Glucose intolerance/diabetes, dyslipidemia, hypokalemia Decreased libido, amenorrhea in women (duet to cortisol-mediated inhibition of gonadotropin release) Irritability, emotional lability, depression, cognitive defects, paranoid psychosis in severe cases Increased susceptibility to infections, leukocytosis with eosinopenia and lymphopenia, hypercoagulability


Excess activation of mineralocorticoid receptor leads to: o Potassium depletion (hypokalemia) o Increased sodium retention (expansion of extracellular and plasma volume  hypertension) Most common cause is primary hypertension Clinical hallmark is hypokalemic hypertension Conn’s Syndrome = aldosterone-producing adrenal adenoma




Cushing’s Disease


 Growth hormone excess

 Prolactin-producing pituitary tumor (prolactinoma), stalk compression  ACTH-producing adenoma

CLINICAL MANIFESTATIONS  Frontal bossing  Increased hand and mandibular enlargement with prognathism  Widened space between lower incisors  Gigantism in children and adolescents  Galactorrhea  Amenorrhea  Infertility

TREATMENT  Transphenoidal surgery (TSS)  Somatostatin analogs (Octreotidem, Lanreotide)  GH receptor antagonist (Pegvisomant)  Dopamine agonists (Cabergoline, Bromocriptine)  radiation  Dopamine agonists (Cabergoline, Bromocriptine)  Surgery (TSS)

    

    

Obesity Thick skin Moon facies Hypertension Purple skin striae

Surgery (selective TSS) Pituitary irradiation Ketoconazole Metyrapone Mitotane



Hirsutism Menstrual disorders Acne Bruising Truncal obesity Proximal muscle weakness Oligomenorrhea Amenorrhea Infertility Decreased vaginal secretions Decreased libido and potency Infertility, decreased muscle mass  Reduced beard and body hair growth  Soft testes  Fine facial wrinkles

 Gonadotropin deficiency

III. TESTS OF PITUITARY INSUFFICIENCY HORMONE TEST Insulin Tolerance Test Growth Hormone GHRH test, L-arginine test, L-dopa test Prolactin TRH test Insulin Tolerance Test CRH test ACTH

           

      

Metyparone Test Standard ACTH Stimulation (Co-syntropin) Test Basal Thyroid Function Tests: T4, T3, TSH


     

TRH Test   LH, FSH

LH, FSH, Testosterone, Estrogen

GnRH Test

 Hormone replacement (testosterone, estrogen, progesterone)

INTERPRETATION Insulin-induced hypoglycemia should normally induce a rise in GH; lack thereof suggest GH deficiency Normal response is a rise in GH Lack thereof suggest GH deficiency TRH should normally induce a rise in prolactin levels Insulin-induced hypoglycemia induces a rise in ACTH and subsequently cortisol Lack of rise in both ACTH and cortisol suggests ACTH deficiency Metyrapone blocks cortisol synthesis causing decreased cortisol and increased ACTH Lack of rise in ACTH suggests ACTH deficiency Normal response is an increase in cortisol Lack of rise in cortisol plus low ACTH suggests ACTH deficiency TSH normally induces a rise in T3 and T4 levels Low TSH with low free thyroid hormones indicate TSH deficiency Normal response is a rise in TSH (unless thyroid hormone levels are increased) Lack thereof suggest TSH deficiency Basal LH and FSH should normally be increased in postmenopausal women Low sex hormones in the setting of low LH and FSH indicate pituitary insufficiency Normal response is a rise in FSH and LH (most adults); lack thereof suggests pituitary insufficiency


CHAPTER 8 NEPHROLOGY I. Introduction to Nephrology II. Fluids and Electrolytes 1. 2. 3. 4. 5. 6.

Water Balance Sodium Potassium Calcium Magnesium Bicarbonate

III. Common Renal Conditions 1. 2. 3. 4. 5. 6. 7.

Abnormalities in Nephrology Acute Kidney Injury Chronic Kidney Disease Urinary Tract Infections Nephrolithiasis Renal Tubular Acidosis Glomerular Diseases




Anion Gap = Na – (Cl +

ANION GAP (SERUM) Na+ = serum sodium Cl- = serum chloride HCO3) HCO3 = serum bicarbonate

Urine Anion Gap = Na + K –

BUN BCR = Crea x 247


ANION GAP (URINE) Na+ = urine sodium K+ = urine potassium Cl Cl- = urine chloride

BUN CREATININE RATIO BUN = serum BUN in mmol/L Crea = serum creatinine in umol/L Interpretation:  Pre-renal azotemia: BCR > 20:1  Oliguric renal failure: BCR 10-15:1

ESTIMATED CREATININE CLEARANCE (COCKROFT – GAULT FORMULA) BW = body weight in kg (140 – age) x BW Crea = serum creatinine in mg/dL = 72 x Crea *For females, multiply result by 0.85

SERUM OSMOLALITY  Balance between the water and the chemicals dissolved in blood  Find out if severe dehydration or overhydration is present SERUM OSMOLALITY

Serum Osmolality = 2(Na + K) + RBS + BUN Na+ = serum sodium; K+ = serum potassium; RBS = serum random blood sugar in mmol/L BUN = serum BUN in mmol/L Interpretation:  Normal osmolality: 280 – 295 mosmol/kg  Increased serum osmolality’ dehydration, poorly controlled DM (DKA, HHS), diabetes insipidus  Decreased serum osmolality: overhydration, diuretic use, SIADH URINE OSMOLALITY (ESTIMATE)  Measure of urine concentration  Large values indicate concentrated urine (i.e., heart failure, dehydration, shock, SIADH)  Small values indicate diluted urine (e.g., diabetes insipidus, renal tubular necrosis, renal failure, pyelonephritis) URINE OSMOLALITY (ESTIMATE) Urine SG = urine specific gravity Urine Osmolality = (Urine SG – 1) x Normal 24-hour urine osmolality = 50-800 mOsm/kg


FE Na =

FRACTIONAL EXCRETION OF SODIUM (FE Na) Urine Na+ = urine sodium Plasma Na+ = plasma sodium Urine Na x Plasma Crea Urine Crea = urine creatinine Plasma Crea = plasma creatinine Plasma Na x Urine Crea Interpretation:  FENa < 1%: seen in pre-renal azotemia  FENa > 2%: seen in oliguric acute renal failure



Water excess = (0.6 x BW in kg) - 0.6 x BW in kg x Actual Na Desired Na

BW = body weight in kg Na+ = serum sodium

CORRECTED CALCIUM Calcium must be “corrected” when the albumin is abnormal This is to correct for the change in total calcium due to the change in albumin-bound calcium/

Corrected Calcium = Actual Ca + [(40 – Albumin) x 0.02]

Actual Ca+ = serum calcium in mmol/L Albumin = serum albumin in g/L

CORRECTED SODIUM In marked hyperglycemia, ECF osmolality increases Serum Na+ falls in proportion to ECF dilution, declining 1.6 mEq/L per 100 mg/dL increase in RBS

Corrected Sodium = Actual Na + 0.016 (RBS – 100)

Actual Na+ = serum sodium RBS = random blood sugar in mg/dL


Na deficit = (Desired Na – Actual Na) x BW in kg x 0.6 Hypokalemia

Potassium deficit =

Desired K – Actual K 0.27


Hypernatremia (Water Deficit)

Water deficit =

Na – 140 140


TBW in Males = 0.6 x Body Weight in kg TBW in Females = 0.5 x Body Weight in kg

Bicarbonate Deficit

Bicarbonate deficit = (Desired HCO3 – Actual HCO3) x BW in kg x 0.4



FLUIDS AND ELECTROLYTES WATER BALANCE I. COMPOSITION OF BODY FLUIDS  Water is the most abundant constituent in the body [50% of body weight in women and 60% in men]  Total body water (TBW): 55-75% intracellular fluid (ICF) and 25-45% extracellular fluid (ECF)  ECF: 25% intravascular [plasma water] and 75% extravascular [interstitial]  Fluid movement between spaces determined by Starling forces  Osmolality: solute or particle concentration of a fluid (mosmol/kg of water) o Major ECF particles: Na+, Cl-, HCO3 o Major ICF particles: K+, organic phosphate esters o Effective osmoles: solutes restricted to ECF or ICF and thus determine the effective osmolality of that compartment o Ineffective osmoles: solutes that do not contribute to water shifts (e.g., urea) across most membranes II. HYPOVOLEMIA A. Causes of Hypovolemia RENAL CAUSES  Osmotic diuresis (e.g., mannitol)  Pharmacologic diuresis/natriuresis (e.g., furosemide)  Hereditary defects in renal transport proteins, mineralocorticoid defects (e.g., deficiency, resistance)  Tubulointerstitial injury (e.g., interstitial nephritis, acute tubular injury, obstructive uropathy)  Excessive renal water excretion (e.g., diabetes insipidus)

EXTRARENAL CAUSES  Fluid loss from GI tract (e.g., impaired GI reabsorption, enhanced fluid secretion)  Insensible losses (evaporation of water from skin and respiratory tract)  Accumulation of fluid within specific tissue compartments (e.g., interstitium, peritoneum, GI tract)

B. Clinical Manifestations  Nonspecific: fatigue, weakness, thirst, postural dizziness, oliguria, cyanosis, abdominal and chest pain, confusion, obtundation  May be accompanied by symptoms of additional electrolyte abnormalities C. Physical Examination Findings LESS RELIABLE    

 Diminished skin turgor  Dry oral mucous membranes

D. Diagnostics DIAGNOSTICS Serum BUN, Creatinine

Serum Aminotransferases (AST, ALT) Cardiac Biomarkers Routine Chemistries and/or Arterial Blood Gases

    

MORE RELIABLE Decreased jugular venous pressure (JVP) Orthostatic hypotension Orthostatic tachycardia In severe cases: peripheral cyanosis, cold extremities, oliguria, altered mental status

EXPECTED FINDINGS Increased due to a decrease in glomerular filtration rate (GFR) Creatinine is more dependable since BUN is influenced by changes in tubular reabsorption (prerenal azotemia), catabolic states, hyperalimentation, GI bleeding and protein intake May be elevate in hypovolemic shock from hepatic ischemia May be elevated in hypovolemic shock from cardiac ischemia Will reveal acid-base disorders depending on the etiology and severity of hypovolemia (e.g. normal anion gap metabolic acidosis from diarrheal illness, elevated anion gap metabolic acidosis from lactic acidosis)


E. Management involves Restoration of Normovolemia and Replacement of Ongoing Losses  Mild hypovolemia: oral hydration and resumption of normal maintenance diet  Severe hypovolemia: IV hydration CLINICAL SCENARIO APPROPRIATE MANAGEMENT Normonatremic /  Normal saline (0.9% NaCl) is the most appropriate resuscitation fluid Hyponatremic Patients  Hypotonic solutions: Hypernatremic Patients o 5% dextrose if water loss only (e.g. diabetes mellitus) o Hypotonic saline if both water and Na+-Cl loss Patients with Bicarbonate  IV bicarbonate (150 mEq of NaHCO3 in 5% dextrose) Loss and Metabolic Acidosis Patients with Severe  pRBC transfusions without increasing hematocrit beyond 35% Hemorrhage or Anemia


Disorders are due to abnormalities in water homeostasis that lead to changes in the relative ratio of sodium to boy water (the absolute plasma sodium concentration tells nothing about a patient’s volume status)

I. HYPONATREMIA  Defined as plasma Na+ 20 mM UNa 20 mM     

Glucocorticoid deficiency Hypothyroidism Stress Drugs Syndrome of inappropriate antidiuretic hormone (SIADH) secretion

HYPERVOLEMIC HYPONATREMIA Increase in total body water greater than increase in total body sodium UNa >20 mM UNa 8-10 mM within the first 24 hours and/or by >18mM within the first 48 hours Response to therapy is unpredictable: ergo, frequent Na monitoring is needed Once therapy instituted, focus on treatment or withdrawal of underlying cause

D. Correcting Sodium Deficit and Hyponatremia (Sample Problem) CORRECT SODIUM DEFICIT SAMPLE CASE 1. Compute for the sodium deficit AP, 60/M, 60 kg, complaining of 3-day history of diarrhea. Na deficit = (desired Na – actual Na) x BW in kg x 0.6 Serum Na+ 123. Ongoing losses of 200 cc/LBM, -8 *desired Na is usually pegged at 125-135 mEq/L times/day [Na+ losses in LBM = 25-50 mEqs/L) 2. Compute for the time needed to infuse Desired Na – Actual Na 0.5 mEq / hr L

Time needed in infuse =

3. Compute for the amount of pNSS needed

Na deficit = (133 – 123) x 60 x 0.6 = 360 + 80 mEqs/L *Desired Na of 133 was calculated by adding 10 mEqs to actual Na + (limit to prevent ODS). We add another 80 mEqs/L deficit to our calculated value since our patient has ongoing losses of 1.6L LBM/day, equivalent to 80 mEqs per day.

Amount of pNSS needed = Computed Na deficit / 154

4. Calculate the drip rate Drip rate =

Amount of pNSS needed time needed to infuse

Time needed to infuse =

133 - 123 0.5 mEqs / hr = 20 hours L

Amount of pNSS needed = 440 / 154 = 2.9 L

Drip rate = 2.9L / 20 hours = 145 cc/hour Sample chart order: Start pNSS 1L x 145 cc/hr for a total of 3 liters, re-check serum sodium q6 to 12 hours II. HYPERNATREMIA  Defined as an increase in plasma Na+ concentration to >145mM  Usually the result of a combined water and electrolyte deficit, with losses of water in excess of those of sodium A. Causes  GI water loss / diarrhea: most common gastrointestinal cause  Insensible water loss  Renal water loss: osmotic diuresis from hyperglycemia, excess urea, post-obstructive diuresis, mannitol  Diabetes insipidus B. Symptoms  Symptoms are explained by cellular shrinkage due to efflux of intracellular water  Primarily neurologic: change in sensorium is the most common manifestation C. Management  Central to the management is correction of the underlying cause: o Chronic hypernatremia (>48 hours): correction must be carried out slowly to avoid central cerebral edema (e.g., correct deficit over 48 hours); plasma sodium should not be corrected >10 mM/d o Acute hypernatremia due to sodium loading can be safely corrected at the rate of 1 mM/h  Water, as much as possible, must be administered per orem or by NGT  Alternatively, D5W can be used with corresponding CBG monitoring D. Correcting Hypernatremia (Sample Problem) CORRECT WATER DEFICIT 1. Compute for the water deficit Na – 140 TBW 140 Total body water (TBW) is 50% of body weight in women and 60% in men Water deficit =

2. Compute for ongoing water losses (optional) aka electrolyte-free water clearance

SAMPLE CASE JR, 80/M, 50 kg, bedridden patient presented with decrease in sensorium at the ER. Na was 155. 24-hour urine tests showed 1800 cc volume, urine Na+ of 35, urine K+ 72. Water deficit =

155 – 140 140

x 50 x 0.6 = 3.2 L

CeH2O = 1.8 (1 – 35 + 72) = 0.4 L 155


CeH2O = Urine Volume (1 – Urine Na + Urine K) Plasma Na

Insensible losses = 10 x 50 = 0.5 L

3. Compute for insensible losses = ~10 mL/kg/day (less if ventilated, more if febrile) 4. Correct the deficit over 48-72 hours (incorporate insensible losses and ongoing water losses to daily water replacement) avoiding correction of >10 mM/day

We therefore correct the water deficit of 3.2 L over 48 hours which is roughly 67 cc/hr (1.6 L/day) of free-water replacement + 0.9 L per day to account for ongoing water losses and insensible losses.

Sample chart order: Choice 1: Replacement via enteral route: Give 270 cc free-water flushes q6 after feeding Choice 2: Replacement via parenteral route: to start IVF D5W (or 0.3 NaCl) 1 L x 67 cc/hr Please do serum sodium q6

POTASSIUM I. HYPOKALEMIA  Defined as plasma K+ 5.5mM  A decrease in renal potassium excretion is the most common cause A. Causes “PSEUDO” HYPERKALEMIA

 Cellular efflux (thrombocytosis, erythrocytosis, leukocytosis, in vitro hemolysis)  Hereditary defects in red cell membrane transport

INTRA- TO EXTRACELLULAR SHIFT  Acidosis  Hyperosmolality (radiocontrast, hypertronic dextrose, mannitol)  Beta-adrenergic antagonists (noncardioselective agents)  Digoxin and related glycosides  Hyperkalemia periodic paralysis  Lysine, arginine, aminocaproic acid  Succinylcholine, thermal trauma, neuromuscular injury, disuse atrophy, mucositis or prolonged

INADEQUATE EXCRETION Inhibition of the RAAS  ACE inhibitors / ARBs / direct renin inhibitors  Blockade of mineralocorticoid receptors (spironolactone, eplerenone)  Blockade of ENaC (amiloride, triamterene) Decreased distal delivery  CHF  Volume depletion


immobilization  Rapid tumor lysis

Hyporeninemic hypoaldosteronism Tubulointerstitial disease  Diabetes  Drugs (NSAIDs, COX-2 inhibitors, beta blockers, cyclosporine, tacrolimus)  Advanced age Renal resistance to mineralocorticoid  Tubulointerstitial diseases  Hereditary (defects in ENaC) Advanced renal insufficiency (CKD, ESRD, AKI) Primary adrenal insufficiency

B. Clinical Manifestations  Clinical manifestations are predominantly cardiac in nature  Associated cardiac arrhythmias include sinus bradycardia, sinus arrest, slow idioventricular rhythms, ventricular tachycardia, ventricular fibrillation and asystole  Classic ECG findings are: o Tall peaked T waves (5.5-6.5 mM) o Loss of P waves (6.5-7.5 mM) o Widened QRS complexes (7-8 mM) o Sinusoidal pattern (>8 mM) C. Management  The first priority is assessment of need for emergency treatment followed by comprehensive workup: o ECG manifestations should be considered as an emergency o Patients with plasma K+ >6.5, even without ECG changes, should be managed aggressively o Patients should be placed on continuous cardiac monitoring  The management of hyperkalemia is divided into stages: 1. Cardioprotection (from arrhythmic effects of hyperkalemia)  Calcium raises the action potential threshold and reduces excitability without changing the resting membrane potential  10 mL of 10% calcium gluconate IV over 2-3 mins with cardiac monitoring  Effect starts in 1-3 minutes and lasts 30-60 minutes  Dose should be repeated if there is no change in ECG findings or if they recur 2. Cellular Redistribution (shifts K+ inside the cells) TREATMENT DOSING PHARMACOKINETICS


Beta Agonists

Bicarbonate (IV)

 10 units regular insulin + D50-50

 Effect in 10-20 mins  Peaks at 30-60 mins  Lasts for 4-6 hours

 10-20 mg nebulized salbutamol in 4 ml pNSS inhaled over 10 minutes

 Effect in 30 mins  Peaks at 90 mins  Lasts for 2-6 hours

 150 mEqs + 1 L D5W

OTHERS  Hypoglycemia is a common side effect, therefore follow with D10W at 5075 ml/h  If glucose > 250 mg/dL, insulin should be given without glucose  Use with caution in patients with cardiac disease  No role in routine treatment of hyperkalemia  Reserved for patients with hyperkalemia and concomitant metabolic acidosis

3. Potassium Excretion TREATMENT IMPORTANT POINTS Cation  Sodium polystyrene sulfonate (SPS) exchanges Na+ for K+ in the GI tract and increased Exchange fecal K+ excretion



  



Given as 15-30 g premade suspension with 33% sorbitol or 30 cc lactulose Full effect only after 24 hours and usually requires repeated dosing every 4-6 hours Loop and thiazide diuretics can be utilized to reduce K+ in volume-replete or hypervolemic patients with sufficient renal function Hemodialysis: most effective and reliable method to reduce plasma K+ concentration


Parathyroid agenesis  Isolated  DiGeorge syndrome Parathyroid destruction  Surgical  Radiation  Infiltration by metastases or systemic diseases  Autoimmune Reduced parathyroid function  Hypomagnesemia  Activating CaSR mutations

HIGH PARATHYROID HORMONE LEVELS (SECONDARY HYPERPARATHYROIDISM) Vitamin D deficiency or impaired 1,25(OH)2D production/action  Nutritional  Renal insufficiency  Vitamin D resistance Parathyroid hormone resistance syndromes  PTH receptor mutations  Pseudohypoparathyroidism Drugs  Calcium chelators  Inhibitors of bone resorption (bisphosphonates, plicamycin)  Altered vitamin D metabolism (phenytoin, ketoconazole) Miscellaneous  Acute pancreatitis  Acute rhabdomyolysis  Hungry bone syndrome after parathyroidectomy  Osteoblastic metastases (e.g., prostate cancer)

B. Clinical Manifestations  Patients may be asymptomatic (if decreases in calcium are relatively mild and chronic) or may present with lifethreatening complications  Moderate to severe hypocalcemia presents with paresthesias caused by neuromuscular activity  Chvostek’s Sign: twitching of circumoral muscles in response to tapping of the facial nerve anterior to the ear  Trousseau’s Sign: carpal spasms induced by inflation of BP cuff to 20 mmHg above the patient’s SBP for 3 minutes  Severe hypocalcemia can induce seizures, carpopedal spasm, bronchospasm, laryngospasm and prolongation of QT interval in the ECG C. Management Acute Symptomatic Hypocalcemia Continuing Hypocalcemia Chronic Hypocalcemia due to Hypoparathyroidism

    

OVERVIEW OF CORRECTION (some examples) Calcium gluconate, 10 mL 10% wt/vol (90 mg or 2.2 mmol) IV, diluted in 50 mL of 5% dextrose solution or pNSS, given IV over 5 mins Calcium gluconate 10% solution 10 mL 1-2 amp SIVP (10-15 mins) Constant IV infusion (10 amps calcium gluconate or 900 mg calcium in 1 L D 5W or pNSS x 24 hours) Elemental calcium 1,000-1,500 mg/day in divided doses (Calcium carbonate 500 mg 1 tab BID-TID) Vitamin D2 or D3 25,000-100,000 U daily or calcitriol [1,25(OH)2D] 0.25-2 mcg/day (Calcitriol 0.25 mcg/cap OD-BID)


III. HYPERCALCEMIA A. Causes of Hypercalcemia COMMON CAUSES OF HYPERCALCEMIA 1. Excessive PTH production  Primary hyperparathyroidism (adenoma, hyperplasia, rarely carcinoma)  Tertiary hyperparathyroidism (long-term stimulation of PTH secretion in renal insufficiency)  Ectopic PTH secretion  Inactivating mutation in the CaSR 2. Hypercalcemia of malignancy  Overproduction of PTHrP (many solid tumors)  Lytic skeletal metastases (breast cancer, myoma) 3. Excessive 1,25(OH)2D production  Granulomatous diseases (sarcoidosis, tuberculosis, silicosis)  Lymphomas  Vitamin D intoxication 4. Primary increase in bone resorption  Hyperparathyroidism  Immobilization 5. Excessive calcium intake  Milk-alkali syndrome  Total parenteral nutrition 6. Other causes  Endocrine disorders (adrenal insufficiency, pheochromocytoma, VIPoma)  Medications (thiazides, vitamin A, antiestrogens) B. Clinical Manifestations

Mild Hypercalcemia (up to 11-11.5 mg/dL)

More Severe Hypercalcemia (>12-13mg/dL) ECG Changes

SIGNS AND SYMPTOMS OF HYPERCALCEMIA  Usually asymptomatic and recognized only on routine calcium measurements  Vague neuropsychiatric symptoms (trouble concentrating, personality changes, depression), peptic ulcer disease, nephrolithiasis or increased fracture risk  Lethargy, stupor or coma  GI symptoms (nausea, anorexia, constipation, pancreatitis)  Bradycardia, AV block, arrhythmias and shortened QT-interval

C. Mechanism of Hypercalcemia in Various Diseases MECHANISM EXAMPLES Excessive PTH Production  Hyperparathyroidism, ectopic PTH secretion Parathyroid Hormone Related  Humoral hypercalcemia of malignancy Peptide (PTHrP) Mediated Excessive 1,25(OH)2D  Tuberculosis, lymphoma, Vitamin D toxicity Increased Bone Resorption  Prolonged immobilization, hyperthyroidism, some malignancies Drugs  Thiazides, anti-estrogens, Vitamin A Excessive Calcium Intake  Iatrogenic, calcium supplements D. Management Volume Expansion (Hydration) Forced Diuresis


      

OVERVIEW OF MANAGEMENT First line treatment of hypercalcemia pNSS x 8 hours (may go up to 1-4 L in 24 hours) Furosemide 20-40 mg IV q8-12h Loop diuretics may be used to enhance Ca excretion but should not be initiated until volume status has been restored to normal Diuresis in a dehydrated patient may worsen hypercalcemia Pamidronate 60-90 mg IV over 2-4 hrs May take up to 24-40 hrs to take effect


 Calcitonin   


Acts within a few hours of its administration (used for life-threatening hypercalcemia) Principally acts through osteoclasts, blocking bone resorption Steroids for malignancies (e.g., multiple myeloma, lymphoma) Dialysis for severe hypercalcemia complicated by renal failure refractory to medical management


Second most abundant intracellular cation Important in different processes which include: o Energy transfer, storage and use o Protein, carbohydrate and fat metabolism o Maintenance of normal cell membrane function o Regulation of PTH

I. HYPOMAGNESEMIA  May present with muscular weakness, tremors, seizures, paresthesias, tetany and nystagmus  ECG findings: nonspecific ST-T changes, prolonged QT interval, PVCs, torsades de pointes and ventricular fibrillation  Usually coexists with hypokalemia and hypocalcemia CORRECTING MAGNESIUM DEFICIT SAMPLE CASE 1. Calculate for magnesium deficit PR, 40/M, diagnosed cased of CHF, presented with Mg2+ of 0.5 Magnesium deficit = Desired Mg – Actual Mg Magnesium deficit = 1 – 0.5 = 0.5

Target Mg2+ is usually 1.0 for patients with cardiac conditions. Otherwise, a target of 0.8 is used 2. In correcting for the deficit, 1 g MgSO4 is given per 0.1 mg Mg2+ deficit

Correct the deficit by starting MgSO4 drip as follows: Start MgSO4 drip: 5g in 250cc D5W x 24 hours (faster drip rates can be used for patients with no volume overload)


Usually given in patients with severe metabolic acidosis (except hypercarbic acidosis) Reacts with H+ ions to form water and carbon dioxide and acts as a buffer against acidosis by raising blood pH CORRECTING BICARBONATE DEFICIT SAMPLE CASE 1. Compute for the estimated bicarbonate deficit PC, 56/M, 60 kg, diagnosed case of CKD V, lost to follow-up after initiation HD, presented at the ER gasping Bicarbonate deficit = (Desired HCO3 – Actual HCO3) x weight in kg x 0.4 ABG showed HCO3 of 9 Desired HCO3 is usually 20-23 in patients with CKD 2. Oral alkali supplementation may be initiated There is no hard and fast rule in choosing the method of correction, always rely on clinical judgment (caution with use of NaHCO3)!

Bicarbonate deficit = (20 – 9) x 60 x 0.4 = 264 mEqs

Sample orders:  NaHCO3 50 mEqs IV bolus q6h x 3 doses, or  NaHCO3 50 mEqs in 250 cc D5W x 8h x 3 cycles  NaHCO3 GrX (650 mg) tabs can be given as well




Polyuria Oliguria Anuria Dysuria

   

DEFINITION Reduction in GFR Abnormal excretion of serum protein o Microalbuminuria: 30-300 mg/d (or mg/g) o Macroalbuminuria: 300-3500 mg/d (or mg/g) o Nephrotic range proteinuria: >3500 mg/d (or mg/g) 24 hour-urine output >3000 mL 24 hour-urine output 3.5g/24 h per 1.73m 2, hypoalbuminemia, edema, hyperlipidemia Urinary Tract  Bacteriuria >105 CFU/mL, infectious agent documented in urine, pyuria, leukocyte casts, Infection frequency, urgency, tenderness Nephrolithiasis  Previous history of stone passage, stone seen on x-ray, renal colic Renal Tubular  Electrolyte disorders, polyuria, nocturia, rencal calcification, large kidneys, renal transport Defects defects

ACUTE KIDNEY INJURY (AKI) I. ETIOPATHOGENESIS  Sudden impairment of kidney function resulting in the retention of nitrogenous and other waste products  Defined by: o Rise from baseline creatinine of at least 0.3 mg/dL within 48 hours or at least 50% higher within 1 week o Reduction in urine output to less than 0.5 mL/kg per hour for longer than 6 hours TYPE DESCRIPTION SOME EXAMPLES  Hypovolemia (e.g. GI losses, poor intake)  Most common form  Due to inadequate renal plasma flow and  Low cardiac output intraglomerular hydrostatic pressure to  Decreased effective circulating volume Pre-renal support GFR (CHF, liver failure)  Involves no parenchymal damage to the  Impaired renal autoregulation (NSAIDs, kidney; rapidly reversed once ACEi, ARBs, cyclosporine) intraglomerular hemodynamics are restored  Most common causes are  Glomerular (Acute GN) o Sepsis  Tubules and interstitium o Ischemia o Ischemia o Nephrotoxins o Sepsis/infection Intrinsic  Ischemia: hypoxia in the renal medulla o Nephrotoxins leads to impaired autoregulation,  Exogenous (iodinated endothelial and vascular smooth muscle contrast, aminoglycosides, damage and leukocyte-endothelial crisplatin, ampho B) adhesion, vascular obstruction and  Endogenous (hemolysis,



rhadbomyolysis, myeloma, intratubular crystals) 

 Post-renal

Occurs when unidirectional flow of urine is acutely blocked, leading to increased retrograde hydrostatic pressure and interference with GFR

   

Vascular o Vasculitis o Malignant hypertension o TTP-HUS Bladder neck obstruction (most common) Prostatic disease Neurogenic bladder Therapy with anticholinergics

II. MAJOR CAUSES, CLINICAL FEATURES AND DIAGNOSTICS ETIOLOGY CLINICAL FEATURES LABORATORY FEATURES  Poor fluid intake / fluid loss  BCR >20%  Heart failure  FeNa 1.018 hypotension, dry mucous  Urine osmolality >500 membranes) mOsm/kg Sepsis-associated AKI

 Overt hypotension not always seen in mild to moderate AKI

 Systemic hypotension, often superimposed on sepsis and those with limited renal reserve such as old age and CKD Nephroxtoxin-Associated AKI (Endogenous) Ischemia-associated AKI


 Traumatic crush injuries, seizures, immobilization


 Recent blood transfusion with transfusion reaction

Tumor Lysis

Multiple myeloma

 High turnover disease (leukemia, lymphoma)  Recent chemotherapy  Age > 60 years  Constitutional symptoms  Bone pain

 (+) culture from normally sterile body fluids  Granular casts and renal tubular epithelial cell casts on urinalysis  Granular casts, renal tubular epithelial cell casts  FeNa >1%  Elevated myoglobin and CK  Heme (+) with few RBC on U/A  Anemia  Elevated LDH  Low haptoglobin  Hyperphosphatemia, hypocalcemia, hyperyuricemia  Monoclonal spike in urine or serum electrophoresis  Low anion gap

COMMENTS  Low FeNa, high SG and urine osmolality may not be seen in CKD & diuretic use  Most diagnostic: Response to restoration of hemodynamics  FeNa may be low particularly early in the course but is usually >1% and osmolality 1% typically  Eosinophilia  Sterile pyuria

 FeNa may be low

 Urine eosinophils of limited diagnostic accuracy


 Non-drug causes: tubulointerstitial nephritisuveitis syndrome, Legionella infection Other causes of Intrinsic AKI  Variable features of skin rash, arthralgias, sinusitis Glomerulonephritis/ (anti-GBM disease), lung Vasculitis hemorrhage (anti-GBM, ANCA-associated, lupus), recent skin infection or pharyngitis TTP/HUS

Atheroembolic disease

Post-renal AKI

 Recent GI infection or use of calcineurin inhibitors  Recent manipulation of the aorta or other large vessels  May occur spontaneously or after anticoagulation  Retinal plaques, palpable purpura, livedo reticularis, GI bleed  History of kidney stones, prostate disease, obstructed bladder catheter or pelvic neoplasm

 Often non-oliguric

 ANA, ANCA, anti-GBM antibody  Hepatitis serologies, cryoglobulins  Blood culture  Hypocomplementemia  ASO titer  Schistocytes on PBS  Elevate LDH  Anemia, thrombocytopenia  Hypocomplementemia  Eosinophiluria (variable)  Variable amounts of proteinuria  No specific findings other than AKI  May have pyuria or hematuria

 Systemic signs of drug reaction often absent  Kidney biopsy may be helpful

 Kidney biopsy may be helpful

 Kidney biopsy may be helpful

 Skin or kidney biopsy can be diagnostic

 Imaging with computed tomography or ultrasound

III. MANAGEMENT MANAGEMENT THERAPY ISSUE Reversal of Renal Insult Ischemic AKI  Restore systemic hemodynamics and renal perfusion through volume resuscitation and use of vasopressors Nephrotoxic AKI  Eliminate nephrotoxic agents  Consider toxin-specific measures Prevention and Treatment of Complications Intravascular volume  Salt and H2O restriction overload  Diuretics, ultrafiltration Hyponatremia  Please see selection on “Sodium” Hyperkalemia  Please see selection on “Potassium” Metabolic acidosis  Sodium bicarbonate (maintain serum HCO3 >15 mmol/L or arterial pH >7.2)  Dialysis in severe cases  Restriction of dietary phosphate intake Hyperphosphatemia  Phosphate-binding agents (e.g., calcium carbonate, calcium acetate, sevelamer hydrochloride, aluminum OH) Hypocalcemia  Calcium carbonate or gluconate (if symptomatic) Hypermagnesemia  Discontinue Mg2+-containing antacids Hyperuricemia  Treatment usually not necessary if 0.5 mg/dL Persistent acute renal failure; complete loss of kidney function >4 weeks LOSS Complete loss of kidney function >3 months


I. ETIOPATHOGENESIS  Spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in GFR  Defined by the KDOQI as kidney damage for > 3 months, as defined by structural or functional abnormalities of the kidney, with or without decreased GFR, manifested by either of the following or GFR 3 months with or without damage o Pathologic abnormalities o Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests A. Leading Categories of Etiologies of CKD  Diabetic nephropathy  Glomerulonephritis  Hypertension-associated CKD (vascular and ischemic kidney disease)  Autosomal dominant polycystic kidney disease  Other cystic and tubulointerstitial nephropathies B. Pathophysiology of CKD  Initiating mechanism specific to the underlying etiology  Progressive mechanisms involving hyperfiltration & hypertrophy of the remaining viable nephrons II. STAGING OF CKD  CKD is alternatively defined by KDIGO as abnormalities of kidney structure or function present for >3 months, with implications for health and is classified (for prognostication/risk for outcome of CKD) based on case, GFR category and albuminuria category (CGA)  ESRD: represents a stage of CKD where the accumulation of toxins, fluid and electrolytes normally excreted by the kidneys results in the uremic syndrome A. Prognosis of CKD by GFR and Albuminuria Categories: KDIGO 2013 PERSISTENT ALBUMINURIA CATEGORIES A1 A2 A3


Normal or high


Normal to mildly increased 1 g/day, BP goal  Heart Failure is 102 bacterial CFU/mL in urine B. Etiology  Uropathogens causing UTI: usually enteric gram-negative rods that have migrated to the urinary tract  Common pathogens o E. coli o Staphylococcus saprophyticus o Klebsiella spp. o Proteus spp. o Enterococcus spp.  In majority of cases, bacteria establish infection by ascending from urethra to bladder  Bacteria can also gain access to the urinary tract by hematogenous spread II. CLINICAL MANIFESTATIONS Cystitis  Dysuria, urinary frequency, nocturia, hesitancy, suprapubic discomfort, gross hematuria (without vaginal discharge)  Mild cases present with low-grade fever with or without lower-back or costovertebral-angle pain Pyelonephritis  Severe cases present with high fever, rigors, nausea, vomiting and flank/loin pain  Urinalysis reveals pyuria (> 5 wbc/hpf of centrifuged urine) & bacteriuria (> 10,000 CFU of uropathogen/mL) Emphysematous  Severe form characterized by production of gas in renal and perinephric tissues Pyelonephritis  Almost exclusive in DM patients Xanthrogranulomatous  Occurs when chronic urinary obstruction, together with chronic infection, leads to Pyelonephritis suppurative destruction of renal tissue


III. DIAGNOSIS DIAGNOSTIC Urinalysis and Urine Dipstick Test Urine Culture Blood Culture Biomarkers

Radiologic Imaging

Other tests

EXPECTED FINDINGS Urine microscopy reveals pyuria (~100%) and hematuria (~30%) Dipstick test for nitrite and leukocyte esterase test can be used in certain areas Detection of bacteria in urine culture is the “gold standard” for UTI Recommended in cases of pyelonephritis to facilitate cost-effective use of antibiotics Not routinely recommended unless the patient presents with signs of sepsis Procalcitonin, mid-regional pro-atrial natriuretic peptide and CRP all not recommended  Not routinely recommended  Considered for patients with: o History of urolithiasis, urine pH > 7.0 or renal insufficiency o Who remain febrile despite 72 hours of treatment o Whose symptoms recur (to rule out nephrolithiasis, obstruction, abscess formation or other complications of pyelonephritis)  Perform specific tests to assess for specific target organ damage (see above)      

IV. MANAGEMENT OF UTI A. Acute Uncomplicated Cystitis  Empiric antibiotic treatment: most cost-effective management approach (pre-treatment urine culture and sensitivity is not recommended and urine microscopy and dipstick test are not prerequisites for treatment)  Patients whose symptoms worsen or do not improve after completion of initial treatment should have a culture done and antibiotics empirically changed pending result of sensitivity testing  Patients in whom symptoms fail to resolve after treatment should be managed as complicated UTI DRUG DOSE Primary Nitrofurantoin macrocrystals (first line) 100 mg QID x 7 days PO Treatment Fostomycin trometamol 3 g PO single dose Fluoroquinolones Ofloxacin 200 mg BID x 3 days PO Ciprofloxacin 250 mg BID x 3 days PO Levofloxacin 250 mg OD x 3 days PO Alternative Norfloxacin 400 mg BID x 3 days PO Treatment Beta-Lactams Amoxicillin-clavulanate 625 mg BID x 7 days PO Cefuroxime 250 mg BID x 7 days PO Cefixime 200 mg BID x 7 days PO Cefpoxodime proxetil 100 mg BID x 7 days PO B. Acute Uncomplicated Pyelonephritis  Hospital admission (and IV antibiotic use, as necessary) is recommended for patients with: o Inability to maintain oral hydration or take medications / concern with compliance o Presence of possible complicating conditions o Severe illnesses with high fever, severe pain, marked debility and signs of sepsis ORAL PARENTERAL Ciprofloxacin Ceftriaxone 500 mg BID x 7-10 days 1-2 g q24h Ciprofloxacin Ciprofloxacin 1000 mg BOD x 7 days 400 mg q12h Extended-Release Levofloxacin Levofloxacin 250 mg OD x 7-10 days 250-750 mg q24h 750 mg OD x 5 days Ofloxacin Ofloxacin 400 mg BID x 14 days 200-400 mg q12h Amikacin 15 mg/kg q24h IV antibiotics can be shifted to any of the above oral antibiotics once afebrile (day 3) and can tolerate drugs PO (guided by GS/CS results) Gentamicin +/- Ampicillin 3-5 mg/kg q24h    

Multi-drug resistant organisms: ertapenem 1 g q24h or piperacillin-tazobactam 2.25-4.5 g q6-8h Aminopenicillins and first-generation cephalosporins: not recommended (high prevalence of resistance) TMP-SMX must be used only if the uropathogen is proven to be susceptible Routine post-treatment culture in patients who are clinically improved is not recommended


C. UTI in Pregnancy  Screening should be done between 9th-17th week AOG, preferably on the 16th week for all pregnant women  The following are considered relatively safe in early pregnancy: o Nitrofurantoin o Ampicillin o Cephalosporins D. UTI in Males Men with uncomplicated UTI Acute bacterial prostatitis Chronic bacterial prostatitis Recurrent bacterial prostatitis Retreatment in the absence of urologic abnormalities

7 to 14 days of fluoroquinolone or TMP-SMX Get cultures and tailor therapy and continue for 2-4 weeks 4-6 weeks of antibiotics 12 weeks of antibiotics 2 weeks 4-6 weeks if repeat culture reveals same organism as initial infecting organism


Calcium salts, uric acid, cysteine and struvite are the common constituents May be asymptomatic and incidentally noted during radiographic studies undertaken for unrelated reasons Common cause of isolated hematuria As the stone traverses the ureter, it may present with pain (beginning at the flank, gradually increasing in severity over the next 20-60 mins, may radiate to ipsilateral groin, testis or vulva) and bleeding  Stone 1000 mg  Hyperlipidemia  Clinical for gout Cysteine  Stone type  Fluids and alkali Stones (1%) Hereditary  Elevated cysteine  D-penicillamine if needed excretion Struvite Stones Infection  Stone type (Mg2+,  Antibiotics and judicious surgery (5%) PO4-, NH3)


Disorder of renal acidification out of proportion to the reduction in GFR Characterized by hyperchloremic metabolic acidosis with normal anion gap TYPE CLINICAL FEATURES TREATMENT  Kidneys unable to acidify urine to pH 3 g/24h proteinuria Hypertension Hypercholesterolemia Hypoalbuminemia Edema/anasarca Microscopic hematuria

       

Minimal change disease Focal segmental glomerulosclerosis Membranous glomerulonephritis Diabetic neuropathy AL and AA amyloidosis Light-chain deposition disease Fibrillary-immunotactoid disease Fabry’s disease

PROTOTYPE DISEASES  Goodpasture’s syndrome  ANCA small-vessel vasculitis (Wegener’s, Churg-Strauss, Microscopic polyangitis)  HSP  Cryoglobulinemia

Basement Membrane Syndromes  Microscopic hematuria  Mild to heavy proteinuria  Hypertension with variable elevations in serum creatinine

   

Anti-GBM disease Alport’s syndrome Thin basement membrane disease Nail-patella syndrome

Glomerular Vascular Symptoms  Vascular injury  Hematuria  Moderate proteinuria         

PROTOTYPE DISEASE Atherosclerotic nephropathy Hypertensive nephropathy Cholesterol emboli Sickle cell disease Thrombotic microangiopathies APAS ANCA small-vessel vasculitis HSP Cryoglobulinemia

Infectious Disease-Associated Syndromes  Variety of inflammatory reactions in glomerular capillaries  Combination of hematuria and proteinuria        

Post-streptococcal GN Subacute bacterial IE HIV Hepatitis B and C Syphilis Leprosy Malaria schistosomiasis


CHAPTER 9 RHEUMATOLOGY I. Approach to Patients with Joint Pains II. Common Conditions in Rheumatology 1. 2. 3. 4. 5. 6.

Osteoarthritis Gouty Arthritis Systemic Lupus Erythematosus Rheumatoid Arthritis Infectious Arthritis Antiphospholipid Antibody Syndrome



APPROACH TO PATIENTS WITH JOINT PAINS I. HISTORY TAKING OF PATIENTS WITH JOINT PAIN QUESTIONS TO ASK REMARKS  Monoarthritis: gout, septic arthritis, knee osteoarthritis (OA), reactive arthritis (ReA)  Oligoarthritis (2-4 joints involved): OA, reactive arthritis, gout What is the number  Polyarthritis (> 5 joints involved): rheumatoid arthritis (RA), systemic lupu erythematosus of joints affected? (SLE), hand OA, chronic gout

What is the mode of onset?

Is there presence or absence of joint inflammation? Is it articular or nonarticular?

Note: psoriatic arthritis has 5 types and can therefore be mono- to polyarticular  Acute versus chronic: o Acute onset examples: gout, septic arthritis o Chronic onset examples: OA; RA; TB arthritis; connective tissue disease (CTD)-related arthritis, e.g., SLE Note: chronic diseases may have acute onset or “flares”, e.g., OA flare, while some acute diseases can become chronic, e.g., chronic tophaceous gout  Inflammation usually presents with at least one of the following: dolor (pain), calor (warmth), rubor (redness), tumor (swelling), and function laesa (loss of function)  Inflammatory arthritis: pain and stiffness in involved joints; worse in the morning or after periods of inactivity (“gel phenomenon”); improves with mild to moderate activity  Non-inflammatory arthritis: pain that worsens with activity and improves with rest  Non-articular causes: bursitis, tendinitis, other soft tissue conditions 

What is the pattern of joint involvement?

Is there systemic involvement?

Pattern of onset: migratory, additive, intermittent o Migratory: joints are sequentially affected where, as one joint settles, another becomes inflamed (e.g. acute rheumatic fever) o Additive: subsequent joints are involved while preceding ones are still inflamed; most common but least specific (e.g., RA) o Intermittent: the same joint is involved in different episodes of inflammation, but the joint is quiescent during intervening periods (e.g., gout) Most commonly involves the eyes and skin, e.g., uveitis, scleritis, malar rash, oral ulcers, photosensitivity

II. PHYSICAL EXAMINATION  Goal is to ascertain the structures involved, nature of the underlying pathology, functional consequences, and presence of systemic or extraarticular manifestations  There are 28 easily examined joints (to be palpated): o Proximal interphalangeal joints (PIPs) o Metacarpophalangeal joints (MCPs) o Wrists o Elbows o Shoulders o Knees A. Pain Differentiation Based on Range of Motion SITE OF PATHOLOGY ACTIVE ROM Referred pain Normal Periarticular pain Decreased Intraarticular pain Decreased B. Definition of Terms SITE OF PATHOLOGY Crepitus Subluxation

 

PASSIVE ROM Normal Can be normal Decreased

DEFINITION Palpable vibratory or crackling sensation elicited with joint motion Alteration of joint alignment such that articulating surfaces incompletely approximate each other



Range of Motion



Enthesitis Epicondylitis

 

Abnormal displacement of articulating surfaces such that the surfaces are not in contact For diarthrodial joints, the arc of measurable movement through which the joint moves in a single plane Loss of full movement resulting from bony hypertrophy, malalignment of articulating structures, or damage to periarticular supportive structures Abnormal shape or size resulting from bony hypertrophy, malalignment of articulating structures, or damage to periarticular supportive structures Inflammation of the enthuses (tendinous or ligamentous insertions in bone) Infection or inflammation involving an epicondyle

C. Grading of Muscle Strength (5-point scale)  No movement 0  Trace movement or twitch 1  Movement with gravity eliminated 2  Movement against gravity only 3  Movement against gravity and some resistance 4  Normal strength 5 III. DIAGNOSTICS  Cannot substitute for clinical evaluation and should never be used as a “screen” for disease  Positive predictive value of many rheumatologic tests is low when these tests are ordered indiscriminately DIAGNOSTICS COMMENTS / EXPECTED FINDINGS  Add little to the evaluation of acute presentations of arthritis (except in cases of Radiographs suspected trauma) but often critical for the assessment of chronic arthritis  Plain radiography is the imaging method of choice  Most reliable means of distinguishing between inflammatory and noninflammatory arthritis is analysis of the WBC in the synovial fluid Arthrocentesis and  Important diagnostic test to rule out septic arthritis and gout Synovial Fluid Analysis  Determine the WBC; detect bacteria by gram stain; look for uric acid crystals under polarized light  Synovial fluid WBC count 100 mg/dL, in which case septic arthritis or gout should be excluded  Values range from 238-516 umol/L (4.0-8.6 mg/dL) in men; 178-351 umol/L (3.0-5.9 mg/dL) in women  Hyperuricemia is associated with gout and nephrolithiasis but levels may not Serum Uric Acid correlate with severity of articular disease  50% of patients with an acute gouty attack will have normal serum uric acid levels  Monitoring may be useful in assessing response to therapy (target: 90% of mixed connective tissue disease Sm: 30% of SLE (specific) Ro (SS-A): 60% of Sjogren’s, subacute cutaneous lupus, neonatal lupus La (SS-B): 50% of Sjogren’s, 15% of lupus Scl-70: 40% of diffuse scleroderma PM-1: polymyositis, dermatomyositis Jo-1: polymyositis with pneumonitis + arthritis RNA polymerase I: 40% of progressive systemic sclerosis Centromere / kinetochore: 75% of CREST (limited scleroderma)



COMMON CONDITIONS IN RHEUMATOLOGY OSTEOARTHRITIS (OA) I. ETIOPATHOGENESIS  Most common joint disease and a leading cause of disability in the elderly  Sine qua non is hyaline articular cartilage loss o Commonly affected joints are the cervical and lumbosacral spine, hip, knee and first metatarsophalangeal (MTP) joints o In the hands, the distal and proximal interphalangeal joints (IPs) and base of the thumb are often affected o Wrist, elbow and ankle are usually spared  Risk factors include age (most important), obesity, repeated joint use  Joint pain is activity-related, starting as episodic and progressing continuously with accompanying brief morning stiffness (2 g per day Up to 2 weeks duration

      

Less systemic side effects compared to oral preparations Steroids: should not exceed 3 times per year in the same joint Hyaluronans: more effective: longer duration of pain control Glucosamine and chondroitin sulfate Opioids (tramadol) Topical capsaicin Surgery (arthroscopic debridement and lavage, meniscectomy, arthroplasty)


GOUTY ARTHRITIS I. ETIOPATHOGENESIS  Metabolic disease that usually affects middle-aged to elderly men and postmenopausal women  Results from increased body urate pool with hyperuricemia  Precipitants of gout: dietary excess, trauma, surgery, excessive ethanol ingestion, hypouricemic therapy and comorbid illness (e.g., stroke, ACS) Asymptomatic  Defined as hyperuricemia in the absence of gouty arthritis and uric nephrolithiasis Hyperuricemia  Hyperuricemia; defined as serum uric acid >7 mg/dL (416 umol/L) in men and >6 mg/dL (357 umol/L) in women Acute Gouty Arthritis  Characterized by acute arthritis initially affecting the MTP of the first toe (podagra) followed by recurring episodes of acute mono- or oligoarthritis Intercritical Gout  Referred to as “interval gout”: the asymptomatic periods between gouty attacks Chronic Tophaceous  Occurs in untreated gouty arthritis, characterized by persistent low grade Gout (CTG) inflammation of joints with sporadic flares  Joint deformities: due to deposition of massive urate crystals forming visible tophi II. DIAGNOSTICS DIAGNOSTICS  Synovial Fluid Analysis Joint Imaging Serum Uric Acid 24h Uric Acid Collection


     

COMMENTS / EXPECTED FINDINGS Strongly negative birefringent needle-shaped monosodium urate (MSU) crystals both intra- and extracellularly Thick chalky paste fluid; WBC 2,000-60,000/uL Joint swelling early in the disease; soft tissue masses Cystic changes with well-defined erosions and overhanging sclerotic margins May be low or normal at the time of attacks >800 mg/24h (over-producers) 11-13 mg/dL, presence of tophi, arthropathy on radiography, nephrolithiasis, tumor lysis syndrome, CKD 2-3 NSAIDS, glucocorticoids, ice compress Colchicine: unless contraindicated (e.g., renal insufficiency), colchicine 0.5 mg TID may be given, then decreased to OD after the acute attack and maintained until uric acid 10 joints (at least 1 small joint) Serology Negative RF and negative anti-CCP antibodies Low-positive RF or low-positive anti-CCP antibodies (< 3 times ULN) High-positive RF or high-positive anti-CCP antibodies (> 3 times ULN) Acute-phase Normal CRP and normal ESR Reactants Abnormal CRP or abnormal ESR Duration of < 6 weeks Symptoms > 6 weeks B. Diagnostic Tests DIAGNOSTICS Serum Markers CBC Synovial Fluid Analysis Joint Imaging

SCORE 0 1 2 3 5 0 2 3 0 1 0 1

COMMENTS / EXPECTED FINDINGS (+) RF or anti-CCP, elevated acute phase reactants Normocytic normochromic anemia Consistent with inflammatory arthritis Juxtaarticular osteopenia (initial finding), soft tissue swelling, joint effusions, symmetric joint space narrowing, joint subluxation & collapse in severe cases

III. MANAGEMENT A. NSAIDS  Formerly viewed as the core of all other RA therapy  Now considered as adjunctive therapy B. Glucocorticoids  Low-moderate doses for rapid disease control before the onset of fully effective DMARD therapy  1- to 2-week burst of glucocorticoids for acute disease flares C. Disease-Modifying Anti-Rheumatic Agents (DMARDS)  Slow or prevent structural progression of RA  Cornerstone of therapy DMARD DOSING Methotrexate 10-25 mg/week PO or SQ (DMARD of choice) Folic acid 1 mg/day given to reduce toxicities Hydroxychloroquine 200-400 mg/day PO Sulfasalazine

500-1500 mg BID PO


10-20 mg/day

     

ADVERSE EFFECTS / COMMENTS Hepatotoxicity, myelosuppression, infection, nauseam diarrhea, interstitial pneumonitis Contraindicated in pregnancy Irreversible retinal damage, rash, cardiotoxicity, blood dyscrasia, nausea, diarrhea Granulocytopenia, hemolytic anemia in persons with G6PD deficiency, nausea, diarrhea Hepatotoxicity, myelosuppression, infection, alopecia, diarrhea Contraindicated in pregnancy

D. Biologics  Protein therapeutics designed mostly to target cytokines and cell-surface molecules  Share the common adverse effect of a potentially increased risk for infection BIOLOGIC MECHANISM Infliximab  Chimeric (part-mouse, part-human) anti-TNF monoclonal antibody Adalimumab,  Fully humanized anti-TNF monoclonal antibody Golimumab


Certolizumab pegol Etanercept Anakinra Abatacept Rituximab Tocilizumab

 Pegylated Fc-free fragment of a humanized monoclonal antibody with binding specificity for TNF  Soluble fusion protein comprising the TNF receptor-2 in a covalent linkage with the Fc portion of IgG1  Recombinant form 1L-1 receptor antagonist  Soluble fusion protein consisting of a domain of human CTLA-4 linked to a portion of human IgG  Chimeric monoclonal antibody against CD-20  Humanized monoclonal antibody against the IL-6 receptor

INFECTIOUS ARTHRITIS I. ETIOPATHOGENESIS A. Pathogenesis  Hematogenous route is the most common route in all age groups  The knee is the most commonly involved joint  Acute bacterial infection typically involves a single joint or a few joints  Subacute or chronic monoarthritis or oligoarthritis suggests mycobacterial or fungal infection  Polyarticular involvement may be seen in RA B. Etiologic Agents  Infants: Group B Streptococcus, Gram (-) enteric bacilli, and Staphylococcus aureus  Young adults & adolescents: N. gonorrhea  Staphylococcus aureus accounts for most non-gonococcal isolates in adults of all ages II. CLINICAL MANIFESTATIONS  Fever (may be absent in immunosuppressed people)  Moderate-severe pain that is uniform around the joint  Musculoskeletal: joint effusion, muscle spasm, decreased range of motion III. DIAGNOSTICS DIAGNOSTICS Acute Phase Reactants CBC Synovial Fluid Analysis

     

Joint Imaging  Cultures

 

COMMENTS / EXPECTED FINDINGS Elevated ESR, CRP Elevated WBC counts with leftward shift Cell counts averaging 100,000/uL with >90% PMN (acute bacterial infection) 10,000-30,000/uL with 5-70% PMN and remainder lympchocytes (TB/fungal infection) Elevated LDH and total protein; decreased glucose Early findings: soft tissue swelling, joint space widening, displacement of tissue planes by distended capsule Late findings: effusions, symmetric joint space narrowing, joint subluxation and collapse in severe cases Blood CS will be (+) for Staphylococcus aureus in 50% of cases Synovial fluid CS will be (+) for Staphylococcus aureus in 90% of cases

IV. MANAGEMENT A. Non-Pharmacologic Management  Repeated arthrocentesis  Surgical drainage/arthroscopic lavage indicated for: o Septic hip o Concomitant osteomyelitis o Prosthetic joint infection


B. Pharmacologic (Antibiotics) Management 1. Recommended Antibiotics Gram-positive smear Gram-negative smear Pseudomonas suspect

EMPIRIC TREATMENT Oxacillin 2 g IV q4; or Nafcillin 2 g IV q4 Cefotaxime 1 g IV q8; or Ceftriaxone 1-2 g IV q24 Add aminoglycoside or 3rd generation anti-pseudomonal cephalosporin

2. Duration of Treatment According to Organism DURATION OF TREATMENT Staphylococcus aureus 4 weeks Pneumococcus/ 2 weeks Pen G 2M units q4 (penicillin-sensitive) or Cefotaxime/Ceftriaxone Streptococcus (penicillin-resistant) Enteric Gram-Negative 3-4 weeks 2nd/3rd generation cephalosporin IV or quinolone IV/PO Bacilli Pseudomonas At least 2 weeks of aminoglycoside plus extended spectrum penicillin or antiaeruginosa pseudomonal cephalosporin

ANTIPHOSPHOLIPID ANTIBODY SYNDROME (APAS) I. ETIOPATHOGENESIS  Autoantibody-mediated acquired thrombophilia characterized by recurrent arterial or venous thrombosis and/or pregnancy morbidity  Classification and nomenclature of antiphospholipid antibodies o Antibodies against cardiolipin (aCL) o Antibodies against B2GPI (anti-B2GPI) o Lupus anticoagulant (LA) II. DIAGNOSIS  Presence of at least 1 clinical + 1 laboratory criterion CLINICAL CRITERIA 1. Vascular thrombosis defined as > 1 clinical episodes of arterial, venous or small vessels thrombosis in any tissue or organ 2. Pregnancy morbidity, defined as: a. > 1 unexplained deaths of a morphologically normal fetus > 10th week of gestation b. > 1 premature births of a morphologically normal neonate before the 34th week of gestation because of eclampsia, severe preeclampsia or placental insufficiency c. > 3 unexplained consecutive spontaneous abortions before the 10th week of gestation


Antiphospholipid antibodies on 2 occasions, 12 weeks apart: 1. LA, and/or 2. Anticardiolipin (aCL), and/or 3. Anti-B2GPI

III. MANAGEMENT  Warfarin (INR 2.5-3.5) after the first thrombotic event  Pregnancy morbidity prevented by combination of heparin with aspirin 80 mg OD  IV immunoglobulin may be considered


CHAPTER 10 ALLERGY AND IMMUNOLOGY I. Introduction to Allergology and Immunology II. Common Conditions in Allergology and Immunology 1. 2. 3. 4.

Allergic Rhinitis Atopic Dermatitis Anaphylaxis Primary Immune Deficiency Diseases




  

ADAPTIVE IMMUNE SYSTEM  Recently evolved system of immune responses mediated by T and B lymphocytes Inherited from invertebrates  Immune responses are based on specific antigen recognition by clonotypic receptors that are products of Bears germ-line encoded pattern recognition receptors (PRRs) that recognize pathogens and effect pathogen gene arrangements elimination  Consists of two limbs: cellular and humoral immunity  Takes longer to activate but generates more effective defense which improves upon repeated exposure to the same microbe Major Components Cellular Immunity Humoral Immunity Cell components o Natural killer cell lymphocytes o Monocytes / macrophages o Dendritic cells o Neutrophils o Basophils  B Lymphocytes and o Eosinophils their product antibodies/  T Lymphocytes o Tissue mast cells immunoglobulins o Epithelial cells Classic and alternative complement pathways and proteins that bind complement components Antimicrobial peptides (defensins, cathelin, protegrin) Cytokines

II. STAGES OF AN IMMUNE RESPONSE (i.e., generalized response to a bacterial skin infection: first time a particular microbe has infected the body) Infiltration of microbes through a breach in the mirror 1 Activation of innate immune system  Bacterial lysis by membrane attack complex (from complement activation) 2  Opsonization (coating of bacteria with complement proteins that facilitate phagocytosis)  Phagocytosis and eventual digestion Amplification of reactions leading to inflammation  Local vasodilation  Increase in vascular permeability 3  Adhesion of inflammatory cells to blood vessel wall  Chemotaxis (chemical attraction of inflammatory cells to the site of injury)  Immobilization of effector cells at site of infection  Activation of relevant cells and molecules to liberate lytic products Generation of adaptive response (while innate response is being established)  Microbial antigens are captured and processed by antigen-presenting cells which are present in most tissues a. Migration to draining lymph nodes 4 b. Antigen presentation to T cells c. Activated T and B cells return blood circulation and enter inflamed, infected tissues together with antibodies secreted by terminally differentiated B cells (plasma cells) Secreted antibodies augment complement activation and phagocytosis 5 Cytokines released by T cells increase antimicrobial activity of phagocytes 6 Some activated T and B cells who are initially activated revert back to a resting state and constitute the body’s pool of memory lymphocytes specific for the infecting microbe  faster and bigger secondary response by lymphocytes 7 during subsequent infection with the same (or closely-related/antigenically similar) microbe Containment of infection and deactivation of inflammatory response 8


Nature of defense strategy that immune system employs in order to eliminate a microbe depends not only on the biological nature of the microbe but also on the tissue compartment in which the infection is concentrated EXTRACELLULAR INTRACELLULAR In fluids or at the surfaces of the infected tissues Inside cytoplasm of cells Sample  Many types of bacteria  Viruses Pathogens  Parasitic worms  Some bacteria  Opsonization by antibodies and complement  phagocytosis  Interferons inhibit intracellular by macrophages and neutrophils  intracellular digestion viral replication Defense  Eosinophil attack (parasitic worms)  Natural killer (NK) cells and Strategy cytotoxic T (Tc) cells  For microbes resistant to intracellular digestion and can deliberately kill infected cells survive and replicate in cytoplasmic vesicles (e.g., mycobacteria): macrophage activation by cytokines III. OTHER IMMUNOLOGY CONCEPTS  Specificity: highly diverse repertoire of antigen receptors which enables recognition of a nearly infinite range of pathogens  Memory: immune memory to enable rapid recall immune responses  Self-discrimination: immunologic tolerance to prevent immune damage to normal “self” tissue IV. IMMUNOPATHOLOGY  Hypersensitivity or allergy: collateral damage to host tissues by immune system  Autoimmunity: immune recognition of self components (e.g. loss of self-discrimination)  Lymphoproliferative disease  Immunodeficiency










Immediate, IgE-mediated

IgG, IgA or IgMmediated

Immune complexmediated


FOUR MAIN CATEGORIES OF TISSUE DAMAGE Physiology Pathology Extrinsic Autoimmune  Extravascular recruitment  Anaphylaxis of immunological  Chronic urticaria  Allergic asthma components  Allergic rhinitis  Parasite expulsion  Incompatible blood  Thrombocytopenia transfusion  Lysis of pathogens by  Pemphigoid extracellular or intracellular  Hemolytic disease of  Goodpasture’s disease veins the newborn  Myasthenia gravis  Hyperacute graft  Thyrotoxicosis rejection  Hemolytic anemia  Neutralization of pathogen-  Local: arthus reaction,  Local: rheumatoid derived factors (e.g. dermatitis toxins) herpetiformis, allergic arthritis alveolitis  Systemic: SLE,  Transport of antigen to  Systemic: serum germinal centers widespread vasculitis sickness, vasculitis  Tuberculosis  Thyroiditis  Defense against  Leprosy  Adrenalitis intracellular parasites  Contact dermatitis  Pernicious anemia  Graft rejection  diabetes



COMMON CONDITIONS IN ALLERGOLOGY AND IMMUNOLOGY ALLERGIC RHINITIS (AR) I. ETIOPATHOGENESIS  Characterized by a constellation of symptoms (sneezing; rhinorrhea; obstruction of the nasal passages; conjunctival, nasal, and pharyngeal itching; and lacrimation) all occurring in a temporal relationship to allergen exposure  Manifestations caused by sensitization of IgE-rich intraepithelial mast cells with allergens II. CLINICAL MANIFESTATIONS  Hallmarks of allergic rhinitis: episodic rhinorrhea, sneezing, obstruction of the nasal passages with lacrimation, pruritus of the conjunctiva, nasal mucosa and oropharynx  Patients may have concurrent nasal polyps and may develop secondary sinusitis III. DIAGNOSIS  Diagnosis depends on accurate history revealing symptoms coincident with potential triggers (pollen, animal dander, house dust mite, work-related allergens)  Other laboratory findings include: o CBC shows modest peripheral eosinophilia o Positive skin test IV. MANAGEMENT  Allergen avoidance is still the most effective form of management  Treatment options include: o Intranasal steroids (most effective agents) o Oral and nasal antihistamines o Oral decongestants o Leukotriene modifiers o Cromones o Topical ipratropium (for rhinorrhea) o Anti-IgE (omalizumab) o Immunotherapy (for intractable cases)  ARIA 2008 Algorithm ALLERGEN AVOIDANCE ↓ ↓ Intermittent Symptoms Persistent Symptoms Mild Moderate to Severe Mild Moderate to Severe Not in preferred order Not in preferred order In preferred order  Oral or intranasal H1-  Oral or intranasal H1-antihistamine antihistamine  Intranasal steroids  And/or decongestant  And/or decongestant  H1-antihistamine or anti-leukotriene  Or intranasal steroid  Or antileukotriene  Or antileukotriene (or cromone) Review after 2-4 weeks  If improved: step down and continue for 1 month o If failure: review compliance and Review after 2-4 weeks diagnosis  If improved: continue for 1 month o Increase intranasal steroid dose o If itch/sneeze: add H1-blocker  If failure: step up o If rhinorrhea: add ipratropium o If blockage: add decongestant or short course oral steroid  If failure: consider specialist referral ↓ ↓ CONSIDER SPECIFIC IMMUNOTHERAPY


ATOPIC DERMATITIS (AD) I. ETIOPATHOGENESIS  Endogenous eczema: “the itch that rashes”  Typically begins in infancy with many patients outgrowing AD as they develop allergic respiratory symptoms  Pathogenesis: genetics, decreased skin barrier function, altered immunology II. CLINICAL MANIFESTATIONS  A chronic or relapsing disease characterized by pruritus and eczematous lesions with a distinctive morphology and age-specific distribution o Infantile (12 years): also flexural with chronic lesions but can also present as chronic hand dermatitis, facial dermatitis with severe eyelid involvement, extensive or erythrodermic diseases  Patients generally have dry lackluster skin with all three stages of skin reactions present: o Acute lesions: erythematous papules with excoriations, vesicles over erythematous skin, serous exudates o Subacute lesions: erythematous, excoriated, scaling papules o Chronic lesions: thickened plaques of skin, lichenification, prurigo nodularis III. DIAGNOSIS: BASED ON THE CONSTELLATION OF CLINICAL FINDINGS DIAGNOSTIC FEATURES OF ATOPIC DERMATITIS (by Hanifiin and Rajka) MAJOR FEATURES (3 of 4) MINOR FEATURES (3 of 23)  Xerosis  Ichthyosis/palmar hyperlinearity/keratosis pilaris  Immediate (type I) skin test reactivity  Elevated serum IgE  Early age of onset  Tendency toward cutaneous infections/impaired cellmediated immunity  Tendency toward non-specific hand or foot dermatitis  Nipple eczema  Cheilitis  Pruritus  Recurrent conjunctivitis  Typical morphology and distribution of skin lesions  Dennie-Morgan infraorbital fold  Chronically relapsing dermatitis  Keratoconus  Personal or family history of atopy  Anterior subcapsular cataract  Orbital darkening  Facial pallor/erythema  Pityriasis alba  Anterior neck folds  Pruritus when sweating  Intolerance to wool and lipid solvents  Perifollicular accentuation  Food intolerance  Course influenced by environmental/emotional factors  White dermographism/delayed blanch IV. MANAGEMENT  Appropriate skin hydration and use of emollients: mainstay of management  Avoidance of irritants  Identification and avoidance of proven allergens  Identification and treatment of complicated/superimposed bacterial, viral or fungal infections  Anti-inflammatory therapy: topical glucocorticoids, topical calcineurin inhibitors  May give sedating antihistamines (hydroxyzine 25-50 mg tab OD HS)


ANAPHYLAXIS I. ETIOPATHOGENESIS  Life-threatening response of a sensitized human after systemic exposure to specific antigen  Hallmark is the onset of some manifestation within seconds to minutes after introduction of the antigen (with the exception of alpha-galactose allergy in beef, lamb or pork)  Angioedematous and urticarial manifestations are attributed to the release of endogenous histamine II. CLINICAL MANIFESTATIONS ORGAN SYSTEM Cutaneous Respiratory Gastrointestinal Cardiovascular

MANIFESTATIONS Pruritus, urticarial, angioedema, flushing Dyspnea, hoarseness, “lump in the throat”, stridor, wheezing Nausea, vomiting, crampy abdominal pain, diarrhea Hypotension

III. DIAGNOSIS  Diagnosis depends on a history revealing the onset of symptoms and signs within minutes after the antigen is encountered  Other laboratory findings include: o Acute emphysema and lung hyperinflation on chest radiography o Eosinophilia o ECG abnormalities reflecting a primary cardiovascular event mediated by mast cells or secondary to blood volume reduction o Elevation of serum tryptase (except for anaphylaxis from food) IV. MANAGEMENT Mild symptoms (pruritus and urticarial) For injected material and insect stings Ancillary agents


        

Epinephrine 0.3-0.5 ml of 1:1000 (1 mg/ml) SC/IM (repeat q5-20 min for severe reactions) Application of tourniquet proximal to the site Epinephrine 0.2 ml of 1:1000 SC/IM Removal without compression of insect stinger (if present) Diphenyhydramine 50-100 mg IM/IV for urticarial/angioedema Aminophylline 0.25-0.5 g IV for bronchospasm Fluids and pressors to maintain intravascular volume Oxygen supplementation and intubation as needed IV glucocorticoids: o May alleviate delayed onset manifestations o Hydrocortisone 200mg IV loading dose then 100mg IV q6h (for late phase reactions)

PRIMARY IMMUNODEFICIENCY DISEASES (PID) I. ETIOPATHOGENESIS  Genetic diseases with primarily Mendelian inheritance  Overall prevalence of PIDs: 5 per 100,000 individuals  Consequence of PIDs vary depending on the function of the molecules that are defective  multiple levels of vulnerability to infection by pathogenic and opportunistic microorganisms o PID involving T cells generally have severe pathologic consequences  The most frequent PIDs are those that predominantly affect B lymphocytes (60-70% of cases) INNATE IMMUNE ADAPTIVE IMMUNE SYSTEM REGULATORY DEFECTS SYSTEM Phagocytic Cells T Lymphocytes Innate Immunity Adaptive Immunity Impaired Impaired Survival,  Impaired production:  Hemophagocytic Development Migration & Function severe congenital  Auto-inflammatory lymphohistiocytoneutropenia (SCN)  Severe  Severe combined syndromes sis (HLH) combined immunodeficiencies  Asplenia  Severe colitis  Autoimmune immune  Hyper-IgE syndrome lymphoprolifer-


 Impaired adhesion: leukocyte adhesion deficiency (LAD)  Impaired killing: chronic granulomatous disease (CGD) Innate Immunity Receptors and Signal Transduction  Defects in Toll-like receptor signaling  Mendelian susceptibility to mycobacterial disease Complement Deficiencies  Classical, alternative and lectin pathways  Lytic phase

deficiencies (SCID)  DiGeorge syndrome

 CD40 ligand deficiency  Wiskott-Aldrich syndrome (WAS)  Ataxia-telangiectasia and otjer DNA repair deficiencies

ation syndrome (ALPS)  Autoimmunity and inflammatory diseases (IPEX, APECED)

B Lymphocytes Impaired Development  XL and AR agammaglobulinemia

Impaired Function  Hyper-IgM syndrome  Common variable immunodeficiency (CVID)

II. CLINICAL MANIFESTATIONS  Most frequent symptom is the presence of recurrent or unusually severe infections  May also present with recurrent allergic or autoimmune manifestations DEFICIENCY EXAMPLE PATTERN OF INFECTION T & B Cell SCID  Viruses, fungi and bacteria T Cell DiGeorge Syndrome  Budding viruses, Candida, Pneumocystis B Cell Hypogammaglobulinemia  Pyogenic bacteria Spleen Splenectomy  Pneumococci, meningococci and Hemophilius influenza Chronic granulomatous  Catalase-positive organisms (e.g. staphylococcus and Aspergillus) Phagocyte disease Leukocyte adhesion  Indolent infection with pyogenic bacteria deficiency  Poor wound healing Complement C3  Pyogenic bacteria C5, C6, C7, C8 or C9  Neisseria III. DIAGNOSIS  Performance of laboratory tests should be guided to some extent by clinical findings  Neutrophils: decreased in SCN, increased in LAD CBC and Cell Morphology  Lymphocytes: to identify T cell deficits  Eosinophils: increased in WAS and Hyper-IgE syndrome  Howell-Jolly bodies in asplenia Chest X-Ray  Loss of thymic shadow in SCID and DiGeorge syndrome Bone X-Ray  Examine metaphyseal ends in cartilage hair hypoplasia Immunoglobulin Serum Levels  IgG, IgA, IgM: B cell immunodeficiencies  IgE: Hyper-IgE syndrome, WAS, T cell immunodeficiency Lymphocyte Phenotype  T and B lymphocyte counts for T cell immunodeficiency and agammaglobulinemia Dihydrorhodamine Fluorescence (DHR)  To assess for reactive oxygen species production by PMNs which is Assay decresed in chronic granulomatous disease Nitroblue Tetrazolium (NBT) Assay CH50, AP50  To assess classic and alternative complement pathways Abdominal Ultrasound  Assess asplenia


CHAPTER 11 HEMATOLOGY I. Introduction to Hematology 1. 2. 3. 4. 5.

Blood Components Definition of Common Terms Findings in Peripheral Blood Smear Common Computations and Formulas in Hematology Common Antiplatelets, Anticoagulants and Fibrinolytics

II. Transfusion Medicine 1. 2.

Blood Typing Rational Use of Blood Products

III. Common Conditions in Hematology 1. 2. 3. 4.

Anemia Thrombocytopenia Bone Marrow Failure Hematologic Malignancies




WBC / Leukocytes Polymorphonuclear Cells (PMN) / Neutrophils

      



 

Eosinophils Basophils Platelets/Thrombocytes

  

DESCRIPTION Contain hemoglobin Responsible for the O2-carrying capacity of the body Integral part of the immune system Responsible for removing old and aberrant cells and attacking infectious and foreign substances Most abundant WBC Usually the first responders to microbial infection, especially bacterial Three major types: o Natural killer/NK cells (cytotoxic innate immunity) o T cells (cell-mediated adaptive immunity) o B cells (humoral adaptive immunity) Largest WBC Migrate from the bloodstream to other tissues and differentiate into resident macrophages Active in parasitic infections and modulate the allergic inflammatory response Release histamine during the inflammatory response Responsible for coagulation / thrombosis


    

Petechiae Purpura

  

Ecchymosis Hemarthosis Hematoma

 


DEFINITION Hemoglobin < 130 g/L in males; 170 g/L in males; >150 g/L in females Hematocrit >0.50 in males; >0.40 in females Platelet count 10 g/dL o Myocardial infarction o Congestive heart failure from severe anemia o End-stage renal disorder B. Surgical Indications for pRBC Transfusion  Acute blood loss >2L or 40% loss of blood volume (whole blood may be considered)  pRBS transfusion may be beneficial for normovolemic patients with acute anemia who have cardiac disease or are at risk of cardiac disease C. Indications for “Prophylactic” Medications  Paracetamol: given only if febrile  Anti-histamine: given only if with previous history of allergy  Treat as necessary  May opt to give leukocyte-depleted products II. PLATELET TRANSFUSION  Cross-matching not required but should be ABO type-specific  Premedication is not necessary A. Platelet Function at Different Levels of Thrombocytopenia PLATELET LEVEL (cell/mm3) BLEEDING TENDENCY At >100,000 Bleeding time is not affected At 10,000 Bleeding time is prolonged At 30 minutes and not related to platelet count At 50,000/mm 3, if with CNS trauma or bleeding maintain platelet count >100,000/mm 3  Massive blood transfusion and with platelet count 5.5x1010 platelets/bag)


1 Unit increases platelet concentrate by 5,000 – 10,000 cells/mm 3


1 Pack (~200-600 cc, equivalent to 4-8 Units of Random Donor Platelet) Advantage: may reduce the risk of infectious disease transmission by reducing the number of donor exposures Corrected Count Increment (CCI) >10,000 within 1 hour and > 7,500 within 24 hours post-transfusion CCI = {(Posttransfusion count-Pretransfusion count)/(Number of platelets transfused x 10)} x BSA

D. Platelets are NOT useful in the following conditions (thrombocytopenia is due to increased platelet destruction)  Drug-induced Thrombocytopenia  TTP, HUS, ITP  Heparin-induced Thrombocytopenia E. Usual Thresholds for Platelet Transfusion  Platelet count 10 mM 1 o 4 points: 58%  Serum bicarbonate >20 mM 1 o 5 points: 90%  Serum glucose >14 mM V. MANAGEMENT A. Early Recognition and Withdrawal of Offending Drug  Supportive measures : fluid and electrolyte replacement, optimal environmental temperature (28-30%), daily eye exam and disruption of early synechiae by an ophthalmologist B. Specific Treatment in the Acute Phase  Corticosteroids: still controversial dexamethasone IV 1.5 mg/kg/day for 3 days  Intravenous immunoglobulin 1g/kg/day for 3 days  Cyclosporine 3-4 mg/kg/day


Cyclophosphamide 100-300 mg/day

VI. COMPLICATIONS  Most common: sepsis from superimposed bacterial infection (S. aureus, Pseudomonas, Enterobacteriae)  Dehydration  Multiple organ system failure  Late complications of mucosal membrane involvement

ERYTHRODERMA / EXFOLIATIVE DERMATITIS I. ETIOPATHOGENESIS  Diffuse erythema and scaling of the skin involving >90% of the total body skin surface area  52% from preexisting dermatoses (psoriasis, spongiotic dermatitis, immunobullous diseases), 20% idiopathic, 15% drug hypersensitivity reaction, 5% cutaneous T cell lymphoma II. CLINICAL MANIFESTATIONS  Erythematous patches that increase in size and coalesce into generalized erythema with a shiny appearance  fine white or yellow scaling  dull red, edema, lichenification, skin induration  Other changes: ectropion, epiphora, palmoplantar keratoderma, nail changes, scaling of the scalp, diffuse effluvium, alopecia  Systemic findings: tachycardia, hyperthermia/hypothermia, high-output cardiac failure, generalized lymphadenopathy, hepatomegaly, splenomegaly, pedal edema, increased susceptibility to infections and sepsis III. MANAGEMENT GENERAL MEASURES  Fluid and electrolyte replacement  Nutritional replacement (folate supplementation, diet with 130% of normal dietary requirements of protein)  Keep in a warm humid environment (30-32oC)  Oatmeal baths, wet dressings on weeping or crusted lesions, bland emollients  Low-potency topical corticosteroids  Sedating antihistamines (hydroxyzine 25-50 mg tab HS, diphenhydramine 25-50 mg cap q4-6h)

     

DIRECTED THERAPY (once underlying etiology is established) Prednisone 1-2 mg/kg/day with taper (for drug reactions, immunobullous diseases, atopic dermatitis) Cyclosporine 4-5 mg/kg/day (for psoriasis, atopic dermatitis) Methotrexate 5-25 mg/week (for psoriasis, atopic dermatitis) Mycophenolate mofetil 1-3 g/day (for psoriasis, atopic dermatitis, immunobullous diseases) Infliximab 5-10 mg/kg (for psoriasis) Etanercept 25mg SC 2x/week (for psoriasis)


CHAPTER 13 NEUROLOGY I. Approach to Patients with Neurologic Conditions II. Review of the Standard Neurologic Exam III. Common Inpatient Cases 1. 2. 3. 4.

Cerebrovascular Disease Subarachnoid Hemorrhage Seizures and Epilepsy CNS Infection



APPROACH TO PATIENTS WITH NEUROLOGIC CONDITIONS DIAGNOSTIC CATECHISM I. DOES THE PATIENT HAVE A NEUROLOGIC PROBLEM? NEUROLOGIC REMARKS PROBLEM  Numbness of the face, arm, or leg especially on one side of the body Focal Neurologic  Hemiparesis/hemiplegia (weakness or paralysis on one side of the body) Deficits  Visual field problems like hemianopia or quadrantanopia  Trouble speaking or understanding  Problem with walking, balance and coordination Increased Intracranial  Main symptoms: headache, papilledema, vomiting Pressure (ICP)  Other symptoms: deteriorating sensorium, Cushing’s triad (hypertension, bradycardia, irregular respiration), anisocoria  Presence of nuchal rigidity, Brudzinski’s, and Kernig’s signs Meningeal Irritation  Most common infectious cause of meningeal irritation: meningitis  Most common non-infectious cause of meningeal irritation: subarachnoid hemorrhage Seizures Discussed in detail in next section II. WHERE IS THE LESION? (ANATOMIC DIAGNOSIS: REMEMBER THE 3L’S) A. Levelize  Central or peripheral?  If central, supratentorial or infratentorial? o Supratentorial structures: cortex and subcortical structures o Infratentorial structures: brainstem and cerebellum B. Lateralize  Right, left or midline  Diffuse (no lateralizing signs, e.g., meningitis & subarachnoid hemorrhage unless with arteritis or vasospasm) C. Localize LESION Cerebrum

    

Brainstem Disease

Cerebellum Spinal cord

      

Root Disease 

DESCRIPTION Discrete deficits, language disorders, intellectual impairment, seizures Differentiate between cortical vs. subcortical lesions Long tract signs (hemiparesis, hemisensory deficits) Crossed signs (contralateral long tract signs, ipsilateral cranial nerve signs) Cranial nerve signs: III, IV, VI Diplopia V Facial sensation is decreased VII Facial muscle weakness VIII Deafness and dizziness IX, X Dysarthria and dysphagia XI Decreased strength of SCM and trapezius muscles XII Dysarthria and tongue deviation Incoordination, clumsiness, ataxia, tremors on voluntary movements, nystagmus Bilateral, often symmetrical deficit but normal neurologic function above the lesion Presence of sensory level differences Autonomic function disturbances (bowel and bladder problems) Signs of upper motor neuron lesions: extensor toe sign, spasticity, hyperreflexia, clonus Pain (hallmark): usually sharp, stabbing, shooting or radiating down the limb Motor: weakness confined to muscles innervated by a nerve root, normal muscle tone, decreased or absent reflexes Sensory loss in a dermatomal distribution


Peripheral Nerve

Neuromuscular Junction

Muscle Disease

 Maneuvers that stretch the root aggravate the pain  Distal sensorimotor deficit  May present as paresthesia or asymmetric weakness but can also be symmetrical like in GBS  Decreases muscle tone & reflexes, may have atrophy over time & fasciculations  Autonomic disturbances (trophic changes like smooth shiny skin or vasomotor changes like temperature dysregulation)  Purely motor; may involve both cranially and spinally innervated muscles  Waxing & waning weakness (fatigable weakness: hallmark of MG)  Normal size and tone of muscles, intact reflexes, no fasciculations  Proximal and symmetrical weakness  Absent sensory signs except for pain and tenderness  No fasciculations  Atrophy with normal or mildly decreased muscle tone and reflexes  Increased muscle enzymes

III. WHAT IS THE LESION? (ETIOLOGIC DIAGNOSIS: REMEMBER VITAMIN C&D) CATEGORIES Vascular Stroke (infarct, hemorrhage) Infectious/Inflammatory Meningitis, encephalitis, brain abscess Trauma Epidural/subdural hematoma, cerebral contusion Autoimmune Demyelinating diseases like MS and GBS, MG Metabolic Nutritional (e.g., Vitamin B12 or B6 deficiency), electrolyte problems, uremia, hyperglycemia, toxic (e.g., lead), drug overdose Idiopathic/Iatrogenic Iatrogenic: post-procedural complications Neoplastic Primary (e.g., meningioma, glioma) versus metastatic Congenital Arteriovenous malformation, muscle dystrophies Degenerative Parkinson disease, Alzheimer’s disease IV. WHAT TESTS SHOULD BE DONE TO ESTABLISH THE DIAGNOSIS? A. Lumbar Puncture (LP) 1. Indications and Contraindications  Obtain pressure measurements and procure a sample of the CSF for examination Indications  Aid in therapy by the administration of spinal anesthetics and occasionally, antibiotics or antitumor agents, or by reduction of CSF pressure  Increased ICP from suspected or known intracranial mass lesion (order imaging before doing an LP) Contraindications  Infection of the lumbar skin or deeper tissues through which the needle must pass  Coagulopathies (platelet count should be > 50,000 & INR 15 seconds or INR >1.7  Blood glucose 400 mg/dL  Sustained pretreatment SBP >185 mmHg or DBP >110 mmHg (those requiring aggressive treatment to lower BP)  Use of novel oral anticoagulants (NOACs) 2. Antithrombotic Therapy  Noncardioembolic ischemic stroke or TIA o Start ASA 160-325 mg/day as early as possible and continue for 14 days o Long-term ASA 80-100 mg/day monotherapy for secondary stroke prevention o Acceptable options for initial therapy:  Clopidogrel 75 mg OD  Aspirin 25 mg plus extended release (ER) Dipyridample 200 mg BID  Cilostazol 100 mg BID  Trifusal 300 mg BID o Choice of antiplatelet should be individualized o Patients with recurrent stroke while on antithrombotic therapy should be re-evaluated for risk factors (no evidence that increasing the dose will provide additional benefits for those who are already taking Aspirin) o Use of LMWH and heparinoids associated with significant reduction in venous thromboembolism but no significant effect on mortality and disability at 6 months 

Cardioembolic stroke (see Cardiology Chapter 2 for further discussion) o Compute for the CHA2DS2-VASc and HAS-BLED score of patients with AF



Benefit of anticoagulation in acute stroke within the first 14 days would be weighed carefully against the risk of hemorrhagic conversion (large infarctions, severe strokes or neurologic deficits and uncontrolled HPN)

3. Neuroprotection (the 5 “H” principle)  Target mean arterial pressure (MAP): 110-130 mmHg  Permissive hypertension during the first 7 days EXCEPT in cases of: o Acute MI o CHF o Aortic dissection Avoid o Acute pulmonary edema Hypotension o ARF o Hypertensive encephalopathy  Treat if SBP >220 mmHg, DBP >120 mmHg and MAP >130 mmHg  Do not use rapid-acting sublingual agents  Use easily titratable IV or short-acting antihypertensive agents o IV Nicardipine (alternatives: hydralazine, labetalol, esmolol) Avoid  Target O2 sat: >94% Hypoxemia  Monitor O2 saturation via pulse oximeter and/or check ABGs Avoid  Target CBG: 140-180 mg/dL Hypoglycemia  No benefit with intensive glycemic control after stroke or  Use isotonic saline (0.9% NaCl) and avoid glucose-containing (D5) IVFs Hyperglycemia Avoid  Target: normothermia Hyperthermia  Relative risk of death or disability increases twofold for every 1 oC increase in body temp  Treat fever with antipyretics and cooling blankets; work-up for source of fever 4. Role of Neuroprotective and Neurorestorative drugs  Remains a matter of preference of the attending physician  Examples: citicholine, cerebrolysin B. Early Specific Management of Hemorrhagic Stroke 1. Medical Treatment  Treat if SBP >180 mmHg since the absence of ischemic penumbra allows for more aggressive BP treatment in ICH  Acute lowering of SBP 3cm who are neurologically deteriorating or have brainstem compression and hydrocephalus from ventricular obstruction o Bleed associated with structural lesions (aneurysms, AVM) if surgically accessible and patient has good overall prognosis o Clinically deteriorating young patients with moderate or large lobar hemorrhage o Ventricular drainage for patients with intraventricular hemorrhage with moderate to severe hydrocephalus


Other patients which may benefit from surgery: o Basal ganglia or thalamic hemorrhage o GCS 5 and above o Supratentorial hematoma with volume >30cc

C. Primary and Secondary Prevention of Stroke Hyertension  Most important modifiable risk factor; 3-4x higher risk of stroke  Degree of BP reduction is more important than the specific agent Diabetes Mellitus  Target HbA1C 70% if life expectancy is Carotid Stenosis at least 5 years and perioperative risk is 20 years (fasting lipid profile: total cholesterol, triglycerides, LDL and HDL) repeated every 5 years Therapeutic lifestyle changes (TLC) Thrombosis Central adiposity Insulin resistance Obesity Weight reduction (caloric restriction: most important component) HMG-CoA reductase inhibitors (Statins) Fibrates Nicotinic acid Atherosclerotic disease of epicardial coronary artery Epicardial arteries (most common: Left Anterior Descending Artery) Branch points in the epicardial arteries 50% stenosis in at least one major lower limb vessel ABI cut off associated with elevated BP, particularly systolic BP Time of the day where myocardial infarction and stroke are more frequent Gold standard for evaluation and identification of renal artery lesions Most common congenital cardiovascular cause of hypertension

Sildenafil or other drugs in that class in previous 24-48 hours Excessive bleeding Right Coronary Artery Nitrates & Calcium Channel Blockers (Nifedipine) Coagulation Necrosis (preserved architecture, faded details) 12 hours after the onset of symptoms Mottling: 4 hours Bright yellow: 1 wk Surrounding red granulation tissue: 2 weeks Gray-white scar: 2 months Q-wave infarction (equivalent to STEMI in Clinical Medicine) Non-Q-wave Infarction (equivalent to NSTE ACS in Clinical Medicine) Dressler’s Syndrome 1st time MI patients (cardiac scar in those with previous MI prevents rupture) 12-Lead ECG Chest pain Cardiac-Specific Troponin T & CardiacSpecific Troponin I Ventricular Fibrillation Pump Failure Pulmonary rales; S3 and S4 gallop sounds Onset of pain and the patient’s decision to call for help Prompt restoration of full contrary arterial patency < 30 min Hemorrhage (Hemorrhagic Stroke: most serious complication) Aspirin Unfractionated Heparin Infarction > 40% 5 days Restenosis White Thrombi Red Thrombi

Cardiac Stroke Hypertension Proteinuria Intermittent Claudication ABI 10 second events where ventilation is reduced by at least 50% from the previous baseline High-Yield Concepts in Mediastinal Masses First step in evaluating a mediastinal mass

Most common lesions in anterior mediastinum

Most common masses in the middle mediastinum

Most common masses in the posterior mediastinum

High-Yield Concepts in DVT and Pulmonary Embolism One of the three major cardiovascular causes of death, along with MI and stroke Causes of pulmonary embolism Population at risk for pulmonary infarcts Usual cause of death from pulmonary embolism Most frequent history in DVT Most frequent history in PE Classic signs of PE Most frequent symptom of PE Most frequent sign of PE Useful rule out test: >95% of patients with normal levels ( duodenum Superior border: cystic and common bile ducts Inferior border: junction of the 2nd and 3rd portions of duodenum Medial border: junction of neck and body of pancreas Peptic ulcer, followed by diarrhea Obtain a fasting gastrin level Secretin study PPIs GI bleeding PPIs (preferably oral if tolerated) Infectious Intestinal metaplasia Involves primarily the fundus and body, with antral sparing Antral-predominant More common type Large, tortuous gastric mucosal folds (not a form of gastritis)

Mucosal disease that usually involves all the rectum & extends proximally to involve all or part of the colon Can affect any part of the GIT from mouth to anus, but


Toxic Megacolon pANCA Positivity (Perinuclear Anti-neutrophil Cytoplasmic Antibodies) ASCA Positivity (Anti-Saccharomyces cerevisiae Antibodies) Markers of Intestinal Inflammation Appendectomy Earliest lesions in CD Pathognomonic feature of CD Most common site of inflammation in CD Earliest radiologic change of UC seen on barium enema Most dangerous local complication of UC Most common ocular complications of IBD Most common genitourinary complications of IBD Mainstay of therapy of mild to moderate UC and Crohn’s Colitis Treatment of moderate to severe IBD First biologic therapy approved for CD Operation of choice for UC Most frequent late complication of IPAA

rectum is often spared (in contrast to UC) Transverse or right colon with diameter of >6 cm and loss of haustrations in severe attacks of UC UC >> CD CD >> UC Fecal lactoferin and calprotectin (leukocyte-derived proteins) Protective against UC, increased risk of CD Aphthoid ulcerations and focal crypt abscesses Granulomas Terminal ileum Fine mucosal granularity Perforation Conjunctivitis, anterior uveitis/iritis, and episcelritis Calculi, ureteral obstruction, and fistulas Sulfasalazine and other 5-ASA agents Glucocorticoids (no role as maintenance therapy) Infliximab (TNF-alpha antibody) Ileal Pouch Anal Anastomosis (IPAA) Pouchitis

High-Yield Concepts in Irritable Bowel Syndrome (IBS) Key symptom / prerequisite clinical feature for Abdominal pain of discomfort the diagnosis of IBS Most consistent clinical feature in IBS Altered bowel habits (most common pattern is constipation alternating with diarrhea) Evidence of anemia Laboratory features that argue against IBS Elevated sedimentation rate Presence of leukocytes or blood in stool Best management for postprandial pain Antispasmodics 30 minutes before meals Initial therapy of choice for IBS-D (Diarrhea Peripherally acting opiate-based agents Predominant) Only antibiotic for IBS with sustained benefit Rifaximin beyond therapy cessation High-Yield Concepts in Diverticular Diseases True Diverticulum Sac-like herniation of entire bowel wall False Diverticulum (Pseudodiverticulum) Only a protrusion of the mucosa through the muscularis propria of the colon (where the vasa recti penetrates) Diverticulitis Inflammation of a diverticulum Air-fluid level in the LLQ on plain abdominal Giant diverticulum of the sigmoid colon film Hinchey Classification System Staging system for predicting outcomes after surgery for perforated diverticulitis Sigmoid diverticula Diagnosis of Diverticulitis is best made with Thickened colonic wall >4 mm these CT findings Inflammation within the pericolic fat + the collection of contrast material or fluid Safety window for barium enema or 6 weeks after an attack of diverticular disease colonoscopy (should not be performed in acute setting due to higher risk of perforation) Best management for massive Diverticular Angiography + coiling (if patient unstable or has had a 6-unit bleed Bleeding in a stabled patient within 24 hours, emergent surgery should be performed) Best management for asymptomatic Diet alterations Diverticular Disease Initial treatment for symptomatic Antibiotics and bowel rest Uncomplicated Diverticular Disease


High-Yield Concepts in Anorectal Disorders Procidentia (Rectal Prolapse) Fecal Incontinences Anismus Mucosal vs Full-thickness Rectal Prolapse Mainstay of Therapy for Rectal Prolapse 3 Hemorrhoidal Complexes in the Anal Canal Most common presentation of Hemorrhoids Hallmarks of an Anorectal Abscess Most common location of Anorectal Abscess Most common location of Anal Fissures Most common location of Internal Opening of Fistula in Ano (FIA) Most common type of FIA Goodsall’s Rule for FIA Best Management for Newly-Diagnoses FIA

Circumferential, full-thickness protrusion of the rectal wall through the anal orifice Involuntary passage of fecal material >10 mL for at least 1 month The result of attempting to defecate against a closed pelvic floor (a.k.a. nonrelaxing puborectalis) Radial vs circumferential grooves around anus Surgical correction Left lateral, right anterior, and right posterior Bleeding and/or protrusion Perianal pain and fever Perianal, followed by ischiorectal Posterior position, followed by anterior (lateral fissure is worrisome, and systemic disorders should be ruled out) Dentate line Intersphincteric, followed by transsphincteric Anterior fistula: straight tract to nearest crypt Posterior fistula: curved tract to enter anal canal at posterior midline Exception: Seton (vessel loop or silk tie placed through the tract)

High-Yield Concepts on Mesenteric Vascular Disease Most common form of Acute Intestinal Strangulated small bowel obstruction, followed by ischemic colitis Ischemia Most prevalent gastrointestinal disease Ischemic colitis complicating cardiovascular surgery Griffith’s point: splenic flexure Most common locations for Colonic Ischemia Sudeck’s point: descending/sigmoid colon Gold standard for diagnosis and management Laparotomy of Acute Arterial Occlusive Disease Gold standard for confirmation of Mesenteric Arterial Occlusion in Chronic Intestinal Mesenteric angiography Ischemia Intervention of choice to maintain hemodynamics in Nonocculsive/Vasopastic Fluid resuscitation Mesenteric Ischemia Optimal treatment for Ischemic Colitis Resection of ischemic bowel & formation of a proximal stoma Most significant indicator of survival in Timeliness of diagnosis and treatment Mesenteric Ischemia Best prognosis of all Acute Intestinal Ischemic Mesenteric venous insufficiency Disorders Marker of Intestinal Nonviability Area of nonfluorescence >5mm in diameter under UV illumination with Woods lamp High-Yield Concepts in Intestinal Obstruction Main differentials for Acute Intestinal Obstruction Most common cause of Small-Intestinal Obstruction Most common cause of Colonic Obstruction Most irritating substances to the peritoneum Hallmark of all forms of Intestinal Obstruction Pathognomonic signs for Small-Bowel Obstruction on plain abdominal film

Adynamic Ileus Primary Intestinal Pseudo-Obstruction Adhesions Colon cancer Hydrochloric acid, colonic contents and pancreatic enzymes Abdominal distention (more prominent in more distal sites of obstruction) Fluid- and gas-filled loops of small intestine “Stepladder” pattern with air-fluid levels Absence or paucity of colonic gas


Most commonly used modality to evaluate postoperative patients for Intestinal Obstruction Cecal diameter that increases likelihood of perforation Most featured complication of Acute Intestinal Obstruction

Abdominal CT (can differentiate between adynamic ileus, partial obstruction, and complete obstruction) >10 cm on plain abdominal film Closed loop: lumen is occluded at two points by a single mechanism (such as fascial hernia or adhesive band), also often with occlusion of blood supply, leading to high pressures and gangrene

High-Yield Concepts in Appendicitis and Peritonitis Most common abdominal surgical emergency Appendicitis Most common cause of appendiceal luminal Fecalith obstruction leading to Acute Appendicitis (AA) Pathognomonic in AA Sequence of abdominal discomfort and anorexia Most useful test in excluding genitourinary Urinalysis conditions that may mimic AA Most common extrauterine condition requiring Appendicitis abdominal operation during pregnancy Most common period of occurrence of AA Second trimester during Pregnancy Best diagnostic exam of AA during pregnancy Ultrasound Cardinal manifestations of Peritonitis Acute abdominal pain and tenderness, usually with fever Most common causes of localized Peritonitis Uncomplicated appendicitis and diverticulitis High-Yield Concepts in Evaluation of Liver Disease Hepatocellular pattern of liver disease Liver injury, inflammation and necrosis predominate Cholestatic pattern of liver disease Inhibition of bile flow predominates Histologic assessment of necroinflammatory activity: Grading of liver disease Acute or chronic Active or inactive Mild, moderate or severe Level of progression of the disease, based on the degree of hepatic Staging of liver disease fibrosis: Early or advanced Precirrhotic or cirrhotic Criterion standard in evaluation of liver disease and most accurate means of assessing grade Liver biopsy and stage Prognostication for cirrhosis and provides standard criteria for listing for liver transplantation (Class B & C); utilizes serum Child-Pugh Score bilirubin, serum albumin, PT-INR and severity of ascites and hepatic encephalopathy More objective means of assessing disease severity; utilizes serum bilirubin, serum Model for End-Stage Liver Disease (MELD) Score creatinine, and PT-INR Indicates cirrhosis with a Child-Pugh score > 7 Liver decompensation (Class B or C) Occurrence of signs or symptoms of hepatic encephalopathy in a person with severe acute Hepatic failure or chronic liver disease Hepatic inflammation and necrosis that Chronic hepatitis continue for at least 6 months Most common and most characteristic Fatigue symptom of liver disease Hallmark of liver disease and most reliable Jaundice marker of severity Most reliable physical finding in examining the Hepatic tenderness liver Best physical exam maneuver to appreciate Shifting dullness on percussion


ascites Major criterion for diagnosis of Fulminant Hepatitis Screening test for Hepatopulmonary Syndrome Most commonly used Liver Function Tests Rate-limiting step in bilirubin metabolism Any bilirubin found in urine Exclusive site for synthesis of serum albumin Only clotting factor not produced in liver Single best acute measure of hepatic synthetic function Most helpful in recognizing Acute Hepatocellular Diseases Differentials for striking elevations in aminotransferases (>1000U/L) ↑ AST > ↑ ALT ↑ ALT > ↑ AST Key events in hepatic fibrinogenesis First indication of worsening hepatic fibrosis Most commonly employed imaging tests for the liver First-line imaging tests for suspected Obstructive Jaundice First test for suspected Budd Chiari Syndrome (Hepatic Vein Thrombosis) Budd-Chiari Syndrome (BCS) vs Cardiac Cirrhosis

Hepatic encephalopathy during acute hepatitis (indicates poor prognosis) Oxygen saturation by pulse oximetry Serum bilirubin, serum albumin, prothrombin time (PT) Transport of conjugated bilirubin into the bile canaliculi (not conjugation itself) Conjugated/direct bilirubin (water-soluble) Hepatocytes Factor VIII Protime (PT) (PT prolongation >5 secs not corrected by parenteral vitamin K administration is a poor prognostic sign in acute viral hepatitis) Elevated aminotransferases/transaminases Viral hepatitis Ischemic liver injury Toxin- or drug-induced liver injury Acute phase of biliary obstruction caused by passage of gallstone into CBD Alcoholic liver disease (AST for San Miguel Beer) Viral hepatitis (ALT is a more specific indicator of liver injury) Stellate cell activation and collagen production Mild thrombocytopenia Ultrasound, CT, MRI Ultrasound and Ct (high sensitivity for biliary duct dilatation) Ultrasound with Doppler Imaging Extravasation of RBCs in BCS (but not in cardiac cirrhosis)

High-Yield Concepts in Complications of Liver Cirrhosis Portal Hypertension (HPN) Elevation of hepatic venous pressure gradient (HVPG) to >5 mmHg Most common cause of Portal HPN in the US Cirrhosis Gastroesophageal varices with hemorrhage 3 primary complications of Portal HPN Ascites Hypersplenism First indication of Portal HPN in Liver Cirrhosis Hypersplenism with thrombocytopenia Palliative procedure to Portal HPN Transjugular Intrahepatic Portosystemic Shunt (TIPS) First-line treatment to control Acute Variceal Endoscopic intervention Bleeding Most common cause of ascites Portal HPN related to cirrhosis Laterality of Hepatic Hydrothorax More common on the right side Recommended Sodium Restriction for Small 60-80 g/day of alcohol for 10 years Women: 20-40 g/day Major enzyme responsible for alcohol Alcohol dehydrogenase metabolism Hepatocyte injury characterized by ballooning degeneration, spotty Hallmark of Alcoholic Hepatitis necrosis, polymorphonuclear infiltrate, and fibrosis in the perivenular and perisinusoidal space of Disse Zieve’s Syndrome Hemolytic anemia with spur cells and acanthrocytes in patients with severe alcoholic hepatitis Cut-off poor prognosis in Alcoholic Hepatitis Discriminant function > 32 Cornerstone of ALD treatment Complete abstinence from alcohol (liver biopsy should not be performed until abstinence maintained for at least 6 months) High-Yield Concept in Non-Viral Hepatitis Cause of most drug hepatotoxicity Examples of direct hepatotoxins Examples of idiosyncratic hepatotoxins Drugs wherein hepatotoxicity is more frequent in patients with underlying CLD Acetaminophen dose producing clinical evidence of liver injury Acetaminophen dose usually associated with fatal fulminant disease Last resort for Acetaminophen Hepatotoxicity Most important adverse effect of Erythromycin Hepatotoxic component of TrimethoprimSulfamethoxazole (TMP-SMX) Autoimmune Hepatitis (AIH)

Phase I toxic metabolite (cytochrome P450) Carbon tetrachloride, acetaminophen, tetracycline, Amanita phalloides (deathcap mushroom) Halothane, isoniazid, chlorpromazine Aspirin, methotrexate, isoniazid, antiretrovirals 10-15 grams > 25 grams Liver transplantation (if with progressive hepatic failure despite NAC therapy) Cholestatic reaction (infrequent) Sulfamethoxazole Chronic disorder characterized by continuing hepatocellular necrosis and inflammation, usually with fibrosis, which can progress to cirrhosis and liver failure Classic syndrome in young women

Type I AIH ANA antibodies (and p-ANCA) Often seen in children, common in Mediterranean Type II AIH Anti-LKM1 Anti-LKM2 Anti-LKM3 Mainstay of treatment for AIH

Anti-LKM antibodies Type II AIH & hepatitis C Drug-induced hepatitis Chronic hepatitis D Glucocorticoid therapy

High-Yield Concepts in Gallbladder and Biliary Diseases 2 major types of Gallstones Cholesterol stones (>80%) Pigment stones (11.3 mmol/L (>1000 mg/dL) Hematocrit >44% Azotemia with BUN >22 mg/dL Abdominal CT Scan Ultrasonography EUS and MRCP (but ERCP still needed for treatment of biliary and pancreatic duct lesions) Avoidance of ERCP for diagnostic purposes in high-risk patients Bowel rest, intravenous hydration with crystalloid, analgesia Enteral-feeding with a nasojejunal tube (vs TPN) CT-guided needle aspiration with Gram stain and culture Gram-negative bacteria of intestinal origin Pancreatic body or tail (only 15% in the head) Abdominal pain Rupture and hemorrhage of the pseudocyst Splenic artery, followed by inferior and superior pancreatic duodenal arteries Alcoholism Cystic fibrosis Abdominal pain or maldigestion and weight loss Secretin stimulation test (abnormal once >60% of pancreatic exocrine function has been lost) Maximal HCO3 concentration


Test Most common cause of pancreatic calcification Cornerstone of pancreatic therapy Most common congenital anatomic variant of the pancreas

Alcohol Pancreatic enzymes Pancreas divisum



NEPHROLOGY HIGH-YIELD PHYSIOLOGY CONCEPTS IN NEPHROLOGY Site of erythropoietin (EPO) production Active form of Vitamin D Contains vasa recta and has longer loops of Henle Components of the juxtaglomerular apparatus Physiologic function of renin Physiologic function of angiotensin I

Physiologic functions of angiotensin II

Site of aldosterone production Aldoesterone actions ADH actions Triggers for ADH secretion Increases GFR

Decreases GFR Principal cells Intercalated cells Tubuloglomerular feedback Glomerulotubular balance Substances with no transport maximum and renal threshold Ascending limb of the loop of Henle is permeable to Descending limb of the loop of Henle is permeable to

Normal pH in various fluid sites

Acid-base abnormalities caused by diuretics

Intact Nephron Hypothesis by Neil Bricker Bricker’s Trade-Off Hypothesis Hyperfiltration Hypothesis by Barry Brenner

Interstitial cells of the peritubular capillaries 1,25-dihydroxycholecalciferol (calcitriol) 1st hydroxylation happens in the liver (via 25-alpha hydroxylase) 2nd hydroxylation happens in the kidney (via 1-alpha hydroxylase) Juxtamedullary nephrons (less common than cortical nephrons) Macula densa (walls of the distal tubule; detects changes in BP) JG cells (walls of the afferent arteriole; secretes renin) Lacis cells (unknown function) None (merely converts angiotensinogen from the liver to angiotensin I) None (merely converted to angiotensin II due to ACE in the lungs) Vasoconstricts afferent and efferent arteriole (efferent>afferent) Systemic vasoconstriction Stimulates thirst Increases ADH, cortisol, epinephrine, norepinephrine and aldosterone Zona glomerulosa of the adrenal cortex Increases Na+ reabsorption, K+ secretion, H+ secretion Insertion of aquaporins (AQP-2) in the collecting ducts Increased plasma osmolarity Decreased blood volume Decreased blood pressure Afferent arteriolar vasodilation Moderate efferent arteriolar vasoconstriction Afferent arteriolar vasoconstriction Efferent arteriolar vasodilation Severe efferent arteriolar vasoconstriction Absorb Na+ and secrete H+ Absorb K+ and secrete H+ Macula densa feedback “Constant load delivered to the distal tubule” Primary mechanism for autoregulation of GFR “Percentage of solute reabsorbed is held constant” Sodium and all passively transported solutes (exhibits gradient-time transport) Solutes (Mnemonic: asinding limb is permeable to solutes) Impermeable to water Water Impermeable to solutes Arterial blood: 7.4 Venous blood, interstitial blood: 7.35 Intracellular fluid: 6.0-7.4 Urine: 4.5-8.0 Gastric HCl: 0.8 Vaginal secretions: 3.5-4.5 Metabolic acidosis: acetazolamide (Mnemonic: acidazolamide) Metabolic alkalosis: loop diuretics, thiazide diuretics Decreases in the number of functioning nephrons causes remaining nephrons to carry a larger burden of transport, systemic function and regulatory function Some physiologic adaptations to nephron loss also produce unintended clinical consequences Some adaptations accelerate the deterioration of residual nephrons


CLINICAL NEPHROLOGY Diagnostic Procedures in Nephrology Standard test for measurement of albuminuria Most useful renal imaging study The only test to establish etiology in early-stage CKD in the absence of a clinical diagnosis Most sensitive test for renal vein thrombosis (RVT) Imagint test for diagnosis of nephrolithiasis

High-Yield Concepts in Renal Replacement Therapy Most common form of renal replacement therapy for AKI

Clear indications for initiation of renal replacement therapy in patients with CKD

Best potential for complete renal rehabilitation Educational programs should be commenced Most common therapeutic modality for ESRD Leading cause of ESRD Dialysis access with highest long-term patency rate Most important complication of arteriovenous grafts Most common acute complication of hemodialysis, particularly among DM patients Preferred buffer in peritoneal dialysis solutions Most common additives to peritoneal dialysis solutions Most common organisms in peritoneal dialysis-related peritonitis Absolute indication for the urgent initiation of or intensification of dialysis prescription

Accurate 24-hour urine collection Renal ultrasound Renal biopsy CT angiography Helical computed tomography radiocontrast enhancement




Hemodialysis 1. Uremic pericarditis 2. Encephalopathy 3. Intractable muscle cramping, anorexia and nausea not attributable to reversible causes 4. Evidence of malnutrition 5. Fluid & electrolyte abnormalities (principally hyperkalemia or ECF volume overload) refractory to other measures Kidney transplantation No later than stage 4 CKD Hemodialysis DM Fistula Thrombosis of the graft and graft failure Hypotension Lactate Heparin Antibiotics Insulin Gram-positive cocci including Staphylococcus (reflecting the origin from the skin) Uremic pericarditis

High-Yield Concepts in Acute Kidney Injury (AKI) Definition of AKI Definition of oliguria Associated with multiple myeloma Most common cause of Acute Renal Failure (ARF) Most common form of AKI Patchy necrosis, PCT & LH affected, relatively short lengths of tubules affected Extensive necrosis, PCT and DT affected, relatively longer lengths of tubules Three broad categories of AKI

Most common clinical conditions associated with prerenal azotemia Most common causes of intrinsic AKI

A rise of at least 0.3 mg/dL within 48 h or 50% higher than baseline within 1 week; or Reduction in urine output to 6 hours 3.5 g/day (patho) or >3.0 g/day (IM) HypoAlbuminemia HyperLidemia MCD MGN DM Nephropathy Renal Amyloidosis FSGS Focal-Segment GS (FSGS) MCD Mnemonic: OHHA Oliguria Hematuria HPN Azotemia PSGN


Key finding in nephritic syndrome

Rapidly-Progressive GN (RPGN) Goodpasture syndrome Alport syndrome Lupus nephropathy RBC cast

Summary of Nephrotic Glomerular Diseases MCD


DM Nephropathy

Renal Amyloidosis

Effacement of foot processes Highly-selective proteinuria, good response to steroids, excellent prognosis Idiopathic but may be caused by SLE, hepatitis B, syphilis, gold, penicillamine, malignancy Diffuse capillary and BM thickening, “spike & dome appearance” with subepithelial IgG and C3 deposits Non-selective proteinuria, poor response to steroids, indolent course Microangiopathy leading to BM thickening 2 types: diffuse and nodular (has Kimmelsteil-Wilson Nodules) Subendothelial/mesangial amyloid deposits PAS-negative, apple-green birefringence on Congo red stain Increasing severity may lead to renal failure

Summary of Nephritic Glomerular Diseases



Goodpasture Syndrome

Alport Syndrome

High-Yield Concepts in Lupus Nephritis Wire-loop appearance Correlate best with the presence of renal disease in lupus nephritis The only reliable method of identifying the morphologic variants of lupus nephritis Has the most varied course of lupus nephritis Describes global, diffuse proliferative lesions involving the vast majority of glomeruli Has the worst renal prognosis without treatment Predisposed to renal-vein thrombosis and other thrombotic complications Diseases with Prominent Renal Vascular Injury Henoch-Schonlein purpura is distinguished clinically from IgA nephropathy by

Caused by GABHS; marked by high ASO titer Most common pediatric cause of nephritic syndrome Hypercellular glomeruli, “lumpy-bumpy” deposits of IgG and C3, subepithelial humps on electron microscopy Self-resolving Poststreptococcal etiology in 50% Renal failure within weeks or months Type I RPGN: anti-GBM antibody-induced disease Type II RPGN: immune complex-mediated disease Type III: RPGN: pauci-immune type Rupture of the basement membrane seen in the EM Anti-GBM antibodies and anti-alveolar BM antibodies Linear pattern of IgG on IF Hematuria and hemoptysis Appears before age 20 Hereditary structural defect in collagen IV Leaky BM (BM splitting on electron microscope) Hematuria, hearing loss, blindness

Lupus nephritis Anti-dsDNA Renal biopsy Classic III Nephritis Classic IV Nephritis Patients with crescents on biopsy Class V Nephritis

Prominent systemic symptoms Younger age ( TSH > ACTH destruction usually occurs in this sequence Most common presentation of tropic hormone failure in childhood Growth retardation Earliest symptom of tropic hormone failure in the adult Hypogonadism Most common cause of hypopituitarism in children associated with Craniopharyngoima WNT signaling pathway


Most common cause of pituitary hormone hypersecretion and hyposecretion syndromes in adults Cut-off size for microadenoma Most common mechanism where suprasellar extension can lead to bitemporal hemianopsia Early sign of optic tract pressure Surgical approach for most pituitary tumors Treatment of choice for prolactinomas Most common pituitary hormone hypersecretion syndrome in both sexes Hallmarks of hyperprolactinemia Most abundant anterior pituitary hormone and major determinant of hepatic IGF-synthesis Major source of circulating IGF-I Most validated test to distinguish pituitary-sufficient patients from AGHD Most serious manifestation of Graves’ ophthalmopathy Most frequent site of thyroid dermopathy Time of major risk for relapse in Graves’ disease in pregnancy Duration of Carbimazole or methimazole – free period prior to radioiodine therapy Duration of PTU-free period prior to radioiodine therapy Absolute contraindications to radioiodine Most common cause of acute thyroiditits in children and young adults Most common clinically apparent cause of chronic thyroiditis Major cause of sick euthyroid syndrome Most common pattern of sick euthyroid syndrome Clinical manifestations of most goiters Venous distention over the neck and difficulty breathing especially when the arms are raised (in large restrosternal goiters) Most frequent cause of acquired hypoparathyroidism in the past Hypoparathyroidism now usually occurs after High-Yield Concepts Related to Thyroid Malignancies Sonographic characteristics of thyroid nodules suggestive of malignancy Benign thyroid neoplasms where risk of malignancy is very low Benign thyroid neoplasms where risk of malignancy is higher and histology is more difficult to interpret Most common malignancy of the endocrine system Most common type of thyroid cancer More common in iodine-deficient regions Surgical treatment in almost all patients with well-differentiated cancer Mainstay of thyroid cancer treatment Most common type of thyroid lymphoma Provides a marker of residual or recurrent disease in medullary thyroid carcinoma Primary management of medullary thyroid carcinoma Main goal in the approach to thyroid nodule Size of most palpable thyroid nodules

Pituitary adenomas < 10 mm diameter Compression of the optic chiasm Loss of red perception Transsphenoidal surgery Dopamine agonists (Cabergoline and Bromocriptine) Hyperprolactinemia Amenorrhea, galactorrhea, infertility GH Liver Insulin-induced hypoglycemia Compression of optic nerve at apex of the orbit Anterior and lateral aspects of the lower leg (Pretibial myxedema) Postpartum period At least 2 days before Several weeks before Pregnancy and breastfeeding Presence of a pyriform sinus (predominantly leftsided) Hashimoto’s thyroiditis Release of cytokines Decrease in total and unbound T3 levels (low T3 syndrome) with normal levels of T4 and TSH Asymptomatic Pemberton’s Sign Surgery for hyperthyroidism Surgery for hyperparathyroidism

Microcalcifications, hypoechogenicity, increased vascularity Macrofollicular (colloid) Normofollicular (simple) Microfollicular (fetal) Trabecular (embryonal) Hurthle cell variant (oncocytic) Thyroid CA Papillary Thyroid Carcinoma Follicular Thyroid Carcinoma Near-Total Thyroidectomy Levothyroxine suppression of TSH Diffuse large-cell lymphoma Elevated serum calcitonin Surgery Identify in a cost-effective manner the small subgroup of malignant lesions > 1 cm


High-Yield Concepts Related to the Adrenal Cortex Cushing’s Syndrome Hypercortisolism due to exogenous steroids Cushing’s syndrome In the overwhelming majority of patients, Cushing’s syndrome is ACTH-producing corticotrope adenoma of the caused by pituitary Most common cause of Cushing’s syndrome overall Medical use of glucocorticoids for inflammatory or immunosuppressive treatment In at least 90% of patients with Cushing’s disease, ACTH excess Corticotrope pituitary microadenoma (often only a is caused by few millimeters in diameter) Ectopic ACTH production is predominantly caused by Occult carcinoid tumors (usually lung) Majority of patients with ACTH-independent cortisol excess Cortisol-producing adrenal adenoma caused by Most prominent features in Cushing’s syndrome are caused by Upregulation of gluconeogenesis, lipolysis and protein catabolism Signs of proximal myopathy become most obvious when Trying to stand up from a chair without the use of hands or when climbing stairs Majority of patients experience psychiatric symptoms mostly in the Anxiety or depression form of Most important first step in the management of suspected Establish the correct diagnosis Cushing’s syndrome Investigation of choice in ACTH-dependent cortisol excess MRI of the pituitary Oral agents with established efficacy in Cushing’s syndrome Metyrapone and Ketoconazole Hyperaldosteronism and Conn’s Syndrome Most common cause of mineralocorticoid excess Primary hyperaldosteronism (Conn’s syndrome) Clinical hallmark of mineralocorticoid excess Hypokalemic hypertension Concurrent measurement of plasma renin and Accepted screening test for primary hyperaldosteronism aldosterone with subsequent calculation of the aldosterone-renin ratio (ARR) Most straightforward test for primary hyperaldosteronism Saline infusion test Imaging of choice for hyperaldosteronism Fine-cut CT scanning of the adrenal region Preferred approach for unilateral lesions Laparoscopic adrenalectomy Medical treatment for hyperaldosteronism Spironolactone Adrenal Malignancy Most solitary adrenal tumors Monoclonal neoplasms Majority of adrenal nodules Inactive adrenocortical adenomas Most common cause of malignant adrenal mass Metastasis originating from another solid tissue tumor (frequently breast and lung) Characteristics of benign adrenal lesions Rounded and homogenous Characteristics of malignant adrenal lesions Lobulated and inhomogeneous Most common histopathologic classification for adrenocortical Weiss Score carcinoma Highly sensitive for the detection of malignancy and can be used to detect small metastases or local recurrence that may not be 18-FDG PET obvious on CT Site of metastasis in adrenocortical carcinoma Liver and lung Capsule violation during primary surgery Major determinants of poor survival in adrenal carcinoma Metastasis at diagnosis Primary treatment in a nonspecialist center Adrenal Insufficiency Characterized by the loss of both glucocorticoids and Primary adrenal insufficiency (AI) mineralocorticoid secretion Only glucocorticoid deficiency is present Secondary AI Most frequent origin of AI Hypothalamic-pituitary Most common cause of primary AI Autoimmune adrenalitis Excluding iatrogenic suppressions, majority of secondary AI are Pituitary or hypothalamic tumors, or their treatment caused by by surgery or irradiation Distinguishing feature of primary AI Hyperpigmentation


Characteristic feature in primary AI Diagnosis of AI is established by Monitoring of glucocorticoid replacement

Hyponatremia (80%) Short cosyntropin test History and PE for signs and symptoms 1 mg hydrocortisone 1.6 mg cortisone acetate Equipotency of steroids can be assumed for 0.2 mg prednisolone 0.25 mg prednisone 0.025 mg dexamethasone Congenital Adrenal Hyperplasia Increased adrenal androgens, decreased aldosterone, decreased 21-beta hydroxylase deficiency (virilizing) cortisol Increased aldosterone, decreased adrenal androgens, decreased 17-alpha hydroxylase deficiency (non-virilizing) cortisol Pheochromocytoma Classic triad in pheochromocytoma Episodes of palpitations, headaches, profuse sweating Dominant sign of pheochromocytoma Hypertension 10% are bilateral 10% are extraadrenal “Rule of 10s” in pheochromocytoma 10% are malignant 10% calcify 10% in children 10% familial First step in diagnosis of pheochromocytoma Measurement of catecholamines Cornerstone for the diagnosis Elevated plasma & urinary catecholamines Most tumors continuously leak this metabolite, which are detected O-methylated metabolites by measurements of metanephrines Most sensitive test which is less susceptible to false-positive Measurements of plasma metanephrine elevations from stress, including venipuncture Ultimate therapeutic goal for pheochromocytoma Complete tumore removal Before surgery, blood pressure should be Consistently 2.5-3.8 cm (>1-1.5 in)

Monitoring response to treatment Dairy products and other foods Calcium carbonate Calcium citrate Estrogen Raloxifene Tamoxifen (but increases risk of uterine cancer in


Osteonecrosis of the jaw is found mostly in cancer patients given high doses of First bisphosphonate to be approved; initially for use in Paget’s disease and hypercalcemia Preferred site for bone mineral density (BMD) scan due to larger surface area and greater reproducibility Fully human monoclonal antibody to RANKL An exogenous PTH analog By far the most common form of glucocorticoid-induced osteoporosis Affected more severely in glucocorticoid-induced osteoporosis Should have measurement of bone mass at both the spine and hip using DXA If only one skeletal site can be measured, it is best to assess the Demonstrated in large clinical trials to reduce the risk of fractures in patients being treated with glucocorticoids Summary of Bone Disorders DISEASE Osteoporosis Osteopetrosis Osteomalacia/rickets Osteitis fibrosa cystica Paget’s Disease

Ca2+ ↓ ↑ -

PO4 ↓ ↓ -

Most reliable and convenient tests for identifying RM in asymptomatic individuals Key regulator of insulin secretion Glucose level that stimulates insulin synthesis Rate-limiting step that controls glucose-regulated insulin secretion

Most potent incretin Major portion of postprandial glucose utilized by Features of diabetes do not become evident until how much beta cells are destroyed Major susceptibility gene in T1DM Central to the development of T2DM Predominantly accounts for increased FPG levels Results in postprandial hyperglycemia

Honeymoon phase Classic sign of diabetic ketoacidosis (DKA)

3 ketone bodies

Etidronate Hip Denosumab Teripararide (1-34hPTH) Therapeutic use of glucocorticoids Trabecular bone Patients on long-term (>3 months) glucocorticoids Spine in individuals < 60 years Hip in individuals > 60 years Only bisphosphonates

ALP ↑ ↑

High-Yield Concepts in Diabetes Leading cause of ESRD, nontraumatic lower extremity amputation and adult blindness Differentiate Type 1a and Type 1b

Screening for DM

postmenopausal women) Zoledronic acid or pamidronate

PTH ↑ ↑ -

NOTES ↓ Bone Mass Thickened, dense bones Soft bones “Brown tumors” Abnormal bone architecture

DM Type 1a: Autoimmune destruction of beat cells, Type 1b: Non-autoimmune destruction of beta cells HbA1C or FPG Glucose >70 mg/dl (3.9 mmol/L) Glucokinase (liver; higher Km, lower affinity, higher Vmax) Hexokinase (everywhere else; lower Km, higher affinity, lower Vmax) Glucagon-like peptide 1 (GLP-1) Skeletal muscle 70-80% HLA region on chromosome 6 Insulin resistance and abnormal insulin secretion Increased hepatic glucose output Decreased peripheral glucose usage All individuals >45 years old every 3 years; screening at an earlier age if overweight (BMI >25) and have one additional risk factor for DM Time when glycemic control is achieved with modest doses of insulin Kussmaul respiration and fruity odor (secondary to metabolic acidosis and increased acetone) Acetoacetate (excreted in the urine) β-hydroxybutyrate Acetone (not used as source of energy)


Extremely serious complication of DKA seen most frequently in children Necessary for DKA to develop Preferred method for detecting ketones that more accurately reflect the true ketone level Synthesized at a 3-fold greater rate than acetoacetate in DKA Preferentially detected by a commonly used ketosis detection reagent (nitroprusside) Consistent finding in DKA and distinguishes it from simple hyperglycemia False-positive reaction with nitroprusside tablet or stick (test for DKA) Central to successful treatment of DKA Acceptable potassium level wherein insulin drip can be started Underlying cause of hyperglycemic hyperosmotic state (HHS)

Prototypical patient of HHS Prominent features of both HHS and DKA Confirms a patient’s need for insulin Symptoms of diabetes usually resolved when glucose is Primary goal in treatment of adults with DM Recommendations on exercise Standard of care in diabetes management Standard method for long-term glycemic control Primary predictor of long-term DM complications Can be used as an alternative indicator of glycemic control when the HbA1c is inaccurate (hemolytic anemia, hemoglobinopathies) Measurement of glycated albumin that reflects glycemic status over the prior 2 weeks Glucose-lowering agents other than insulin are ineffective in type 1 DM and should not be used for glucose management of severely ill individuals with type 2 DM Major toxicity of metformin Major side effects of GLP-1 agonists Major side effects of alpha-glucosidase inhibitors Most common side effects of bile acid-binding resins Effectively raises HDL, but high doses (>2 g/d) may worsen glycemic control and increase insulin resistance Should not be used if hypertriglyceridemia is present Most serious complication of therapy for DM Predictor of poor outcome in hospitalized patients Preferred in ICU or in a clinically unstable setting (absorption of SC insulin is variable) Preferred over insulin analog for IV insulin infusion (less expensive and equally effective) Preferred method for managing patients with T1DM in the perioperative period or when serious concurrent illness is present Most crucial period of glycemic control in pregnancy Type 1 vs Type 2 Diabetes Mellitus CHARACTERISTICS Usually occurs in those 3.3 mEq/L Relative insulin deficiency and inadequate fluid intake Elderly with T2DM and history of polyuria, weight loss, and diminished oral intake leading to mental confusion, lethargy or coma Volume depletion and hyperglycemia Low C-peptide level < 200 mg/dL (11.1 mmol/L) HbA1C < 7.0% 150 min/week (distributed over at least 3 days) of moderate aerobic physical activity Self-monitoring of blood glucose Measurement of HbA1C HbA1C Albumin Fructosamine assay Except amylin analogs and alpha-glucosidase inhibitors Lactic acidosis Nausea, vomiting and diarrhea Diarrhea, flatulence, abdominal distention Gastrointestinal Nicotinic acid Bile acid-binding resins Hypoglycemia Hyperglycemia Insulin infusions Regular insulin Insulin infusion Soon after fertilization

TYPE 1 + +



DKA is the most common complication Strong polygenic genetic predisposition HLA-DR3, -DR4 Depleted beta cells Islet leukocytic infiltrate Islet amyloid deposit High-Yield Concepts in DM Complications Microvascular manifestations of DM Macrovascular manifestations of DM Leading cause of blindness between ages 20 and 74 Blindness is primarily the result of Non-proliferative DM retinopathy Hallmark proliferative DM retinopathy Best predictors of development of retinopathy Duration of DM in patients with non-proliferative retinopathy Most effective therapy for DM retinopathy Treatment of proliferative retinopathy Treatment of macular edema Microalbuminuria Fibrin caps, capsular drops, Kimmelstiel-Wilson nodules Optimal therapy of DM nephropathy Preferred therapy for DM nephropathy Pigmented pretibial papules or diabetic skin spots Most common site of foot ulcers Optimal therapy for foot ulcers and amputation Most common site of ulceration Most helpful diagnostic for infected foot ulcer Most specific modality for osteomyelitis Osteomyelitis best treated by Most common form of diabetic neuropathy Most commonly involved nerve in mononeuropathy Most prominent GI symptoms in DM Primary goal in gastrointestinal and genitourinary dysfunction in DM Most common pattern of DM dyslipidemia High-Yield Concepts in Hypoglycemia Limiting factor in the glycemic management of diabetes Most common cause of hypoglycemia Second only to drugs as causes of hypoglycemia Whipple’s Triad (in insulinoma)

Critical diagnostic findings when plasma glucose is 20 years Prevention Panretinal laser photocoagulation Focal laser photocoagulation 30-299 mg/d in a 24-h collection or 30-299 ug/mg creatinine in a spot collection (preferred) DM nephropathy (nodular glomerulosclerosis) Prevention by control of glycemia Renal transplantation from a living related donor DM dermopathy Great toe or metatarsophalangeal (MTP) areas Prevention Plantar surface of the foot Culture from debrided ulcer base or from purulent drainage or aspiration of wound MRI of the foot Prolonged antibiotics (IV then oral) and possible debridement of infected bone Distal symmetric polyneuropathy (frequently presents with distal sensory loss) CN III (heralded by diplopia) Delayed gastric emptying and altered small- and large-bowel motility Improved glycemic control Hypertriglyceridemia and reduced HDL

Hypoglycemia Drugs used to treat DM or by exposure to other drugs, including alcohol Serious illnesses such as renal, hepatic or cardiac failure, sepsis and inanition 1. Symptoms consistent with hypoglycemia 2. Low plasma glucose measured with a precise method (not a glucose monitor) 3. Relief of symptoms after the plasma glucose level is raised Plasma insulin concentration >3 uU/mL (>18 pmol/L), Plasma C-peptide concentration >0.6 ng/mL (>0.2 nmol/L),


Lower limit of the fasting plasma glucose concentration Obligate metabolic fuel for the brain under physiologic conditions Major site of endogenous glucose production Hepatic glycogen stores are able to sustain glucose needs for Glycemic maintenance goals in hospitalized patients First defense against hypoglycemia Second defense against hypoglycemia Third defense against hypoglycemia Compromises physiologic defense against hypoglycemia (particularly decrements in insulin and increments in glucagon and epinephrine) Compromises behavioral defense against hypoglycemia (ingestion of carbohydrates) Hypoglycemia in non-beta cell tumors is due to Prototypical cause of endogenous hyperinsulinism Ingestion of an insulin secretagogue Exogenous insulin High-Yield Concepts Related to the Gonads Defined as the inability to conceive after 12 months of unprotected sexual intercourse Probability of achieving pregnancy in one menstrual cycle Emerging as the method of choice for testosterone measurement Most important step in the evaluation of male infertility Normal ejaculate

Most common cause of androgen deficiency in acute illness Most common chromosomal disorder associated with testicular dysfunction and male infertility Glandular breast tissue that is >4 cm in diameter and often tender Most effective therapy if gynecomastia is of long duration Most common cause of female infertility Most widely used form of hormonal contraception Midcycle pelvic discomfort that is thought to be caused by the rapid expansion of the dominant follicle at the time of ovulation Precocious puberty in boys Delayed puberty in boys Precocious puberty in girls Delated puberty in girls

and Plasma proinsulin concentration >5.0 pmol/L Approximately 70 mg/dL (3.9 mmol/L) Glucose (may also use ketones in prolonged fasting after 2 weeks) Liver Approximately 8-12h 140-180 mg/dL Decreased insulin Increased glucagon Increased epinephrine Defective glucose counterregulation Hypoglycemia unawareness Overproduction of insulin-like growth factor II (“big IGF-II”) Insulinoma Causes hypoglycemia with increased C-peptide levels Causes hypoglycemia with low C-peptide levels

Infertility Fecundability (normal value in young couples: 20%) Liquid chromatography tandem mass spectrometry (LCMS/MS) Semen analysis Volume = 2-6 mL Sperm counts >20 million/mL Motility of >50% >15% normal morphology Hypogonadotropic hypogonadism Klinefelter Syndrome (47 XXY) True gynecomastia Surgery Abnormalities in menstrual function Oral contraceptives Mittelschmerz Before age 9 Absence of secondary sexual characteristics by age 14 Before age 8 Absence of secondary sexual characteristics by age 13

ENDOCRINOLOGY AND BIOCHEMISTRY CORRELATION Basic Biochemistry of Lipids Long chain of carboxylic acid with no double bond Long chain of carboxylic acid with one double bond

Saturated fatty acid Monounsaturated fatty acid


Long chain of carboxylic acid with two or more double bonds Fatty acids associated with increased risk of atherosclerosis Essential fatty acids Immediate precursor of prostaglandins End product of fatty acid synthesis 2 primary bile acids (Mnemonic: Starts with a letter “C”: Primary) 2 secondary bile acids 2 molecules conjugated to bile acids to convert them to bile salts Clinical manifestation of lipid malabsorption Spherical macromolecular complexes composed of a neutral lipid core surrounded by a shell of amphipathic lipoproteins, phospholipid and nonesterified cholesterol Protein moiety of lipoproteins Transport dietary triglycerides and cholesterol from intestine to tissues Transports triglycerides from liver to tissues Delivers cholesterol into cells Reverse cholesterol transport Shuttles Apo C-II and Apo E in the blood Mediates chylomicron secretion Activates lipoprotein lipase Mediates uptake of chylomicron remnant Binds to LDL receptor and mediates VLDL secretion Activates LCAT to produce cholesteryl esters in HDL Degradation of TAG stored in adipocytes Degradation of dietary TAG in small intestine Degradation of TAG circulating in chylomicrons Degradation of TAG remaining in IDL Major component of lung surfactant Only glycerophospholipid that is antigenic Reservoir for arachidonic acid in the membranes and precursor for IP3 and DAG Important constituent of myelin Diseases involved in Lipid Metabolism Alcohol leads to fat accumulation in the liver Cerebrohepatorenal syndrome Accumulation of phytanic acid due to deficiency of alpha-hydroxylase Hypoglycin from unripe fruit of the akee tree inactivates medium- and short-chain acyl CoA dehydrogenase Genetic absence of lipoprotein lipase leads to excess TAGs and chylomicrons that deposit in the liver, skin and pancreas LDL receptor deficiency leads to elevated LDL cholesterol with increased risk for atherosclerosis and coronary artery disease Accumulation of fat in intestinal enterocytes and hepatocytes, with deficiency in fat-soluble vitamins and essential fatty acids Mental retardation from accumulation of GM2 ganglioside Mental retardation from accumulation of sphingomyelin Mental retardation with enlarged liver and spleen from accumulation of glucosylceramide Diseases Involved in Carbohydrate Metabolism Flatulence, cramps and diarrhea after ingestion of dairy products Severe fasting hypoglycemia, hepatomegaly, elevated glycogen in the liver Cardiomegaly and heart failure from impaired glycogen metabolism

Polyunsaturated fatty acid Trans-fatty acids and Saturated fatty acids Linoleic acid and Linolenic acid Arachidonic acid Palmitic acid Cholic acid and Chenodeoxycholic acid Deoxycholic acid and Lithocholic acid Taurine and Glycine Steatorrhea Lipoproteins Apoproteins Chylomicrons VLDL LDL HDL HDL Apo B-48 Apo C-II Apo E Apo B-100 Apo A-1 Hormone sensitive lipase Pancreatic lipase Lipoprotein lipase Hepatic TAG lipase Dipalmitoylphosphatidylcholine (Lecithin) Cardiolipin Phosphatidylinositol Sphingomyelin

Fatty liver Zellweger Syndrome Refsum’s Disease Jamaican Vomiting Sickness Type I Hypertriglyceridemia Type IIA Hypercholesterolemia Abetalipoproteinemia Tay-Sachs Disease Niemann-Pick Disease Gaucher’s Disease

Lactose intolerance Von Gierke Disease (Glucose 6-phosphatase deficiency) Pompe (“Pump”) Disease (Lysosomal acid maltase deficiency)


Hepatomegaly, milder form of Von Gierke Disease Myoglobinuria with strenuous exercise Decreased NADPH in RBCs leads to hemolytic anemia due to poor RBS defense against oxidizing agents Recurrent pyogenic infections due to impairment of respiratory burst of neutrophils and monocytes Cataracts within a few days of birth, vomiting and diarrhea after milk ingestion, lethargy, hypotonia, mental retardation Galactosemia, galactosuria, cataracts in early childhood Benign fructosuria Fructosuria, severe hypoglycemia, lactic acidosis, liver damage, jaundice

Cori Disease (Debranching enzyme deficiency) McArdle Syndrome (Skeletal muscles glycogen phosphorylase deficiency) G6PD deficiency (rate limiting enzyme of pentose phosphate pathway) Chronic Granulomatous Disease (NADPH oxidase deficiency) Classic Galactosemia (Galactose 1puridyltransferase deficiency) Galactokinase deficiency Fructokinase deficiency Fructose intolerance (Aldolase B deficiency)



INFECTIOUS DISEASES COMMON INFECTIOUS DISEASES Two Important Mosquito Borne Infections Influenza-like syndrome with maculopapular rash and severe pains in muscles and joints (breakbone fever) Most important parasitic disease in man Comparison of the Different Malaria Species P. FALCIPARUM Asexual Cycle 48 hours Periodicity Malignant Tertian RBC preference All ages Parasitemia Highest Merozoites 0 Gametocytes Banana-shaped Cerebral malaria Yes Recrudescence Yes Relapse No Drug resistance Many

P. VIVAX 48 hours Benign Tertian Young RBCs Low 12-24 Large round No No Yes Few

High-Yield Concepts in Malaria Recurrence of symptoms after a temporary abatement (2-4 weeks) Return of disease after its apparent cessation (1-6 months) due to reactivation of hypnozoites Screens for presence of malarial organisms For species identification in malaria Highest yield of thick and thin smears Punctuate granulation present in RBCs invaded by P. ovale and P. vivax Coarse granulations present in RBC invaded b P. falciparum Fine dots present in RBCs invaded by P. malariae Malarial or Durck granulomas are seen in Acute renal failure in malaria Septic shock in malaria Areas of high endemicity in malaria Areas of chloroquine-resistance in malaria

Dengue Malaria

P. MALARIAE 72 hours Benign Quartan Old RBCs Lowest 6-12 Compact No Yes No Few

Recrudescence Relapse Thick smears Thin smears Blood sample taken during fever 2-3 hours after peak Schuffner dots (Schuffner dots = P. Ovale & Vivax, SOVrang daming dots!) Maurer dots (Mnemonic: coMMa-shaped = P. falciparuM) Ziemann dots Cerebral malaria Blackwater fever Algid malaria Palawan, Kalinga Apayao, Ifugao, Agusan del Sur Palawan, Davao del Norte, Compstela Valley

Natural Course of Typhoid Fever WEEK PRESENTATION 1 Stepwise fever, anorexia, malaise, relative bradycardia and bacteremia 2 Abdominal pain, bloating, constipation, rose spots, hepatosplenomegaly jaundice 3 Bleeding, ileitis, pneumonia 4 Recover or death POST Chronic carrier state High-Yield Concepts Related to Leptospirosis Most severe form of leptospirosis Most common cause of death in leptospirosis Drug of choice against severe leptospirosis

P. OVALE 48 hours Benign Tertian Young RBCs Low 8 Small round No No Yes Few

CULTURE SOURCE Blood, bone marrow Urine, rose spots, bone marrow Stool, bone marrow Bone marrow Bile, stool, bone marrow

Weil’s Syndrome (presents with severe jaundice) Massive pulmonary hemorrhage leading to respiratory failure Ceftriaxone


Prophylaxis for leptospirosis exposure


Comparison of Trematode Infections TREMATODE TRANSMISSION S. japonicum Penetrates skin P. westermanii Ingested with raw crab C. sinensis Ingested with raw fish


High-Yield Concepts Related to Schistosomiasis Intermediate host of S. japonicum Intermediate host of P. westernii Systemic hypersensitivity in schistosomiasis resembling serum sickness Areas of endemicity of schistosomiasis

INTERMEDIATE HOSTS Snail Snail and crab Snail and fish

TREATMENT Praziquantel Praziquantel Praziquantel

Oncomelania quadrasi (snail) Sundathelphusa philippina (mountain crab) Katayama fever Sorsogon, Samar, Leyte, Oriental Mindoro, Bohol & all of Mindanao except Misamis Oriental

High-Yield Concepts Related to Tetanus & Rabies Clostridium tetani (spore is at one end so organism looks like a Anaerobic, gram-positive, spore-forming rods tennis racquet) Histopathologic finding in Rabies Negri bodies (not colored black!) Rabies is invariably fatal when encephalitis develops Early brainstem dysfunction because of

ANTI-INFECTIVES Antibiotic Classification Based on Action

Bactericidal Antibiotics

Bacteriostatic Antibiotics

Very Finely Proficient At Murder! Vancomycin Fluoroquinolones Penicillins Aminoglycosides Metronidazole We’re ECSTaTiC about bacteriostatics! Erythromycin Clindamycin Sulfamethoxazole Trimethoprim Tetracycline Chloramphenicol

Penicillins DRUG Penicillin G Methicillin Ampicillin Ticarcillin/Piperacillin Carbenicillin

CHARACTERISTIC Narrow spectrum penicillins Penicillinase-resistant penicillins Extended-spectrum penicillins Antipseudominal penicillins

SIDE EFFECT Hypersensitivity Interstitial Nephritis Pseudomembranous Coloitis Hypertension, Hypervolemia, Bleeding

Remembering the Penicillins Pen V is Oral, ipinapasok sa Vunganga Pen G is IV: You inGect Pen G Use naf (nafcillin) for Staph AMPicillin = AMPed up penicillin amOxicillin = greater Oral bioavailability


Organisms Susceptible to Amoxicillin Amoxicillin HELPS kill Enterococci Haemophilus influenza Escherichia coli Listeria monocytogenes Proteus mirabilis Salmonella spp. enterococci Cephalosporins DRUG Cefazolin Cefamandole Cefoperazone Ceftazidime Cefepime Ceftriaxone

DESCRIPTION SIDE EFFECT 1st generation cephalosporin, high bone penetration, surgical Hypersensitivity reaction prophylaxis, greatest gram positive coverage 2nd generation cephalosporin, added gram negative coverage Disulfiram reaction 3rd generation cephalosporin, Pseudomonas coverage Disulfiram reaction Most efficacious cephalosporin for Pseudomonas aeruginosa 4th generation cephalosporin, broad spectrum activity (both gram positive and gram negative) Best CNS penetrance

Some important points about Cephalosporins Microbes covered by 1st generation cephalosporins KEPs Klebsiella spp. E. coli Proteus spp. Remembering 1st Generation Cephalosporins FADer, help me FAZ my PHarmacology boards! CeFADroxil CeFAZolin CePHalothin CePHapirin CePHradine CePHalexin Organisms Susceptible to Second Generation Cephalosporins HEN has KEPS Haemophilus influenzae Enterobacter aerogenes Neisseria spp. Klebsiella pneumoniae Escherichia coli Proteus mirabilis Serratia marcescens Remembering Second Generation Cephalosporins In a FAMily gathering, you see your FOXy cousin wearing a FUR coat and drinking TEa. CeFAMandole CeFOXitin CeFURoxime CefoTEtan or FAC! LORA the PROfessional AZhOLE is still on the FONe. CeFAClor LORAcarbef CefPROzil CefmetAZOLE CeFONicid


Cephalosporins causing Disulfiram Reaction Cefamandole Cefmetazole

Cefotetan Cefoperazone

Remembering Third Generation Cephalosporins FEnge PO ng PERA to FIX my TTTTTV! CeFEtamet CefPOdoxin CefoPERAzone CeFIXime

Protein Synthesis Inhibitors DRUG Chloramphenicol

REMARKS Binds to 50S subunit


Binds to 30S subunit

Erythromycin Azithromycin Clindamycin Linezolid Aminoglycosides DRUG Gentamicin Tobramycin Streptomycin Spectinomycin Amikacin Neomycin

CefTazidime CefoTaxime CefTizoxime CefTibuten CefTriaxone

SIDE EFFECT Aplastic Anemia Gray Baby Syndrome Tooth Enamel Discoloration Photosensitivity Diarrhea, cholestatic jaundice

Binds to 50S subunit, Drug of choice for penicillin-allergic patients Binds to 50S subunit, highest volume of distribution, single dose administration for certain indications Binds to 50S subunit, anaerobic coverage Binds to 50S subunit, for Vancomycin-resistant organisms

REMARKS Prototype aminoglycoside Bactericidal Binds to 50S subunit Treatment of ocular infections Tuberculosis Treatment of drug-resistant gonorrhea Widest spectrum of activity Has pseudomonal coverage Narrow therapeutic window Treatment of hepatic encephalopathy

SIDE EFFECT Nephrotoxicity Ototoxicity

Remembering Aminoglycosides Mean GiANTS canNOT kill anaerobes. Gentamicin Amikacin Neomycin Tobramycin

Streptomycin Nephrotoxicity Ototoxicity Teratogen AminOglycosides require O2 for transport. They won’t work under anaerobic conditions.

Sulfonamides DRUGS Sulfamethoxazole TMP-SMX

Fluoroquinolones DRUG Ciprofloxacin

REMARKDS SIDE EFFECT Blocks Dihydropteroate Synthase Sequential blockade in folate synthesis Hypersensitivity (SJS, TEN), Commonly used for UTI kernicterus, hemolysis in patients with G6PD deficiency

REMARKS 2nd generation quinolone Used for UTI and GIT infections

SIDE EFFECT Tendinitis


3rd generation quinolone Used for pulmonary infection 4th generation quinolone Broad spectrum of activity, anaerobic coverage Treatment of ocular infections 4th generation quinolone Diabetes mellitus


Moxifloxacin Gatifloxacin

Anti-Mycobacterial Agents DRUG REMARKS Isoniazid Bactericidal Inhibits mycolic acid synthesis Rifampicin Bacteriostatic Inhibits DNA-dependent RNA polymerase Ethambutol Bacteriostatic Inhibits arabinogalactan synthesis Pyrazinamide Bacteriostatic but bactericidal on actively dividing MTB Streptomycin Bactericidal, binds to 30S

SIDE EFFECT Neurotoxicity, hepatotoxicity, sideroblastic anemia, drug-induced lupus, potent CYP450 inhibitor Red orange urine, hepatotoxicity Visual dysfunction (retrobulbar neuritis, color blindness) Hyperuricemia, most hepatotoxic Nephrotoxicity, ototoxicity

Other Important Things to Remember About Anti-Mycobacterials INH Injures Neurons and Hepatocytes R = Rifampicin (RNA polymerase inhibitor, Red-orange body fluids, Rapid development of resistance, Revs up cytochrome P450 (inducer) Hepatotoxicity: Iso a Red Pyre! [Isoniazid < Rifampin < Pyrazinamide] Drugs Used for Leprosy DRUG REMARKS Most active drug against M. leprae Dapsone Inhibits folate synthesis Rifampicin Inhibits DNA-dependent RNA polymerase Delays onset of dapsone resistance Clofazimine Phenazine dye Binds to guanine bases Other Antimicrobials DRUG Aztreonam Clavulanic Acid Meropenem Metronidazole Nitrofurantoin

SIDE EFFECT Methelmoglobinemia Red-orange urine Skin discoloration

REMARKS SIDE EFFECT Silver bullet against gram-negative bacteria Beta-lactamase inhibitor Drug of last resort Broad spectrum of activity Anaerobic and antiprotozoal coverage Treatment of pseudomembranous colitis Treatment of urinary tract infections

CNS toxicity Disulfiram reaction, metallic taste, neurotoxicity Pulmonary fibrosis

Antibiotics Drugs of Last Resort I AM your Last Shot at Victory! Imipenem Amikacin Meropenem Linezolid Streptogramins Vancomycin Antifungals DRUG Amphotericin B

REMARKS Most efficacious antifungal drug Forms artificial pores

SIDE EFFECT Nephrotoxicity (RTA, ATN)


Ketoconazole Fluconazole Griseofulvin Nystatin

Antivirals DRUG Acyclovir Ganciclovir Foscarnet Amantadine Oseltamivir Lamivudine Ribavirin

Topical treatment of dermatophytosis and Gynecomastia candidiasis CYP450 inhibitor Prophylaxis and treatment of candidiasis and cryptococcosis Interferes with fungal microtubules Potent CYP450 inducer Treatment of candidiasis (oropharyngeal, esophageal, vaginal) Swish and swallow or suppository preparations

REMARKS SIDE EFFECT Treatment of HSV and VZV Crystalluria Requires activation by viral thymidine kinase Treatment of CMV Requires activation by viral thymidine kinase Treatment of HSV, VZV and CMV Does NOT require viral thymidine kinase activation Prevents viral uncoating Cerebellar dysfunction, Influenza A coverage Livedo reticularis Neuraminidase inhibitor Drug of choice for influenza Treatment of hepatitis B infection Treatment of hepatitis C and RSV infection

Some Important Points about FOScarnet and AMANTADINE FOScarnet pyroFOSphate analog AMANTADINE A man to dine takes off his coat. Amantadine prevents uncoating. Blocks influenza A and rubellA Causes problems with the cerebellA Anti-Retroviral Drugs DRUG REMARKS Nucleoside reverse transcriptase inhibitor (NRTI) Zidovudine Requires phosphorylation Primary drug for HIV Prevents vertical transmission of HIV Non-nucleoside reverse transcriptase inhibitor Delavirdine (NNRTI) No phosphorylation required Indinavir Protease inhibitor Enfuvirtide Maraviroc

SIDE EFFECT Lactic acidosis


Fat redistribution syndrome, hyperlipidemia, insulin resistance Fusion inhibitor, binds gp41 subunit Binding inhibitor, CCR5 antagonist

Remembering NNRTIs Never Ever Deliver Nucleosides Nevirapine Efavirenz Delavirdine Remembering Protease Inhibitors All protease inhibitors end with –navir NAVIR (never) TEASE a PROTEASE


Anti-Malarial Drugs DRUG Chloroquine Quinine Primaquine Mefloquine, Malarone Doxycycline ArtemetherLumefantrine

REMARKS SIDE EFFECT Primary drug for malaria Retinal damage, hearing loss Prevents heme polymerization into hemozoin For chloroquine-resistant and severe malaria Hypoglycemia, cinchonism Drug of choice for pregnant patients with malaria Eradication of hypnozoites of P. vivax and ovale Chemoprophylaxis (chloroquine-resistant areas)

Anti-Protozoal Drugs DRUG Dioxanide furoate Metronidazole

Nitazoxanide TMP-SMX PyrimethamineSulfadiazine Suramin + Melarsoprol Nifurtimox Stibogluconate Anti-Helminthic Drugs DRUG Mebendazole

Albendazole Diethylcarbamazine Ivermectin Pyrantel pamoate Thiabendazole Praziquantel Niclosamide

Chemoprophylaxis (multi-drug resistant areas) Drug of choice for malaria in the Philippines (P. falciparum)

REMARKS Asymptomatic cyst carriers of E. histolytica Amoebic dysentery Trichomoniasis Bacterial vaginosis Cryptosporidium parvum infection Pneumocystis jirovecii pneumonia Toxoplasmosis African sleeping sickness Chagas disease Leishmaniasis

REMARKS Inhibits helminthic microtubules Ovicidal Inhibits helminthic microtubules Ovicidal and larvicidal Drug of choice for hydatid disease (echinococcosis) Drug of choice for filarial disease and Loa loa SE: filarial fever Drug of choice for Strongyloides and Onchocerca SE: Mazzotti reaction Drug of choice for Enterobius infection Drug of choice for Trichinosis Drug of choice for trematodes and cestodes except echinococcosis Back-up drug to Praziquantel

BASIC BACTERIOLOGY Steps in Gram Staining (remember V-I-A-S) STEP PROCEDURE 1 Primary stain 2 Mordant 3 Decolonizing Agent 4 Counterstain

REAGENT Crystal Violet Iodine Acetone Safranin


Atypical Bacteria (based on gram staining) NAME REASON Mycobacteria Too much lipid in cell so dye cannot penetrate Spirochetes Too thin to see Mycoplasma No cell wall Legionella Chlamydiae Rickettsiae

Poor uptake of counterstain Intracellular Intracellular

Generalization in Bacteria All bacteria have cells compose of peptidoglycan except All gram-positive bacteria have NO endotoxin except All bacterial capsules are composed of polysaccharide except All exotoxins are heat-labile except Bacterial Oxygen Metabolism Obligate Aerobes Facultative Anaerobes Microaerophiles Obligate Anaerobes Bacterial Culture Media Clostridium perfringens Corynebacterium diphtheria Group D streptococci Staphylococcus spp. N. meningitides, N. gonorrhoeae from sterile sites N. gonorrhoeae from nonsterile sites Haemophilus influenzae Mycobacterium tuberculosis Vibrio cholera Bordatella pertussis Legionella pneumophila Campylobacter jejuni Borrelia burgdorferi Mycoplasma pneumoniae Pseudomonas aeruginosa Salmonella, Shigella Leptospira interrogans

ALTERNATIVE Acid-fast stain Dark field microscopy Non Use serologic studies Silver stain Locate for inclusion bodies Giemsa/Tissue stains

Mycoplasma pneumoniae Listeria monocytogenes Bacillus anthracis Staphylococcal enterotoxin

Nocardia, Bacillus cereus, Neisseria, Pseudomonas, Bordetella. Legionella, Brucella, Mycobacterium Staphylococcus, Bacillus anthracis, Corynebacterium, Listeria, Actinomyces, Mycoplasma Streptococcus, spirochetes (Borrelia, Leptospira, Treponema), Campylobacter Clostridium, Bacteroides

Egg yolk Tellurite Bile esculin Mannitol salts Chocolate Thayer-Martin Chocolate + factors X and V Lowenstein-Jensen Thiosulfate citrate bile salts (TCBS) Bordet-Gengou Charcoal-yeast extract Skirrow Barbour-Stoenner-Kelly (BSK) Eaton Cetrimide Xylose-Lysine-Deoxycholate (XLD) Ellinghausen-McCullough-Johnson-Harris (EMJH)



ALLERGY AND RHEUMATOLOGY High-Yield Concepts in Basic Immunology B cell surface marker and EBV receptor Most potent and effective APCs (antigen presenting cells) in the body Major receptor for antigen in B cells Majority of total serum immunoglobulins, able to cross the placenta Antibody secreted in mucosal surface as dimer, most produced antibody overall First immunoglobulin to appear in the immune response and initial antibody synthesized by neonates Protein molecules capable of activating up to 20% of T-cell pool resulting in widespread immune response Binding of an opsonized target cells to an FC receptor bearing effector cell resulting in the lysis of the target Rapid, first-line immunity involving neutrophils, macrophages, dendritic and natural killer cells Learned, high-specific immunity involving T and B cells and antibodies and utilizing memory cells Expressed in all nucleated cells, presents endogenous intracellular antigens to CD8 cytotoxic T-cells Expressed only on APCs and present exogenous or extracellularly engulfed antigens to CD4 T-helper cells Involved with MHC1 – activates CD8 and macrophages via IFN-y Involved with MHC2 – secretes IL4, 5, 6, 13 recruiting eosinophils stimulating antibody production Release cytotoxic granules (perforin, granzyme) and activates apoptosis Facilitates phagocytosis by coating antigen Acute phase reactants that are increased during inflammation Proteins that are decreased during inflammation Classigcal – IgG or IgM mediated Alternative – Microbial surface proteins Lectin – Mannose or other sugars Complement proteins involved in anaphylaxis (anaphylatoxins) Induces neutrophil chemotaxis The key effector cell in the biologic response in allergic rhinitis, asthma and anaphylaxis and urticarial Neutrophil chemotaxis Components of Slow Reacting Substance of Anaphylaxis (SRS-A) Most effective means of controlling allergic disease Common Cytokines and Their Function IL1 IL2 IL3 IL4 IL5 IL6 IL8 IL10 IL12 TNF alpha IFN gamma

CD21 (other B cell markers: CD19 and 20) Dendritic cells IgM and IgD IgG IgA IgM Superantigen ADCC (antibody dependent cellular cytotoxicity) Innate immunity Adaptive immunity MHC (Major Histocompatibility Complex) 1 MHC 2 TH1 (T-Helper 1) TH2 (T-Helper 2) Cytotoxic T cells Opsonins (IgG and C3b) Serum Amyloid A, CRP, Ferritin, Fibrinogen, Hepcidin Albumin, Transferrin Complement Pathways C3a, 4a, 5a C5a Mast cells Leukotriene LTB4 Leukotriene LTC4, LTD4, LTE4 Allergen avoidance

Fever, activates osteoclasts Stimulates all types of T cells Stimulates bone marrow stem cells Induces B cell growth and IgE production Induces eosinophil growth and IgA production Fever, stimulates acute phase proteins Major neutrophil chemotactic factor Modulates inflammatory response (together with TGF-B) Differentiates T cells into TH1; activates NK cells Stimulates septic shock, vascular leakage, recruitment of leukocytes Activates macrophages; increases antigen presentation


Common Autoantibodies and Associated Diseases Anti-Ach Receptor Anti-Basement Membrane Anti-Glutamate Decarboxylase Anti-Jo-1, Anti-SRP, Anti-Mi-2 Anti-Microsomal, Anti-Thyroglobulin, Anti-TPO (Thyroid Peroxidase) Anti-Mitochondrial Anti-Smooth Muscles TSI (TSH-Receptor Stimulating Immunoglobulin), Anti-TPO Anti-U1 RNP (Ribonucleoprotein) Anti-Centromere Anti-Scl-70, Anti-Topoisomerase 1

MG Goodpasture’s Syndrome Type DM Dermatomyositis, Polymyositis Hashimoto’s Thyroiditis Primary Biliary Cirrhosis (PBC) Autoimmune Hepatitis Graves’ Disease Mixed Connective Tissue Disese (MCTD) Limited Scleroderma, CREST Syndrome Diffuse Syndrome

High-Yield Concepts in Systemic Lupus Erythematosus (SLE) Female, joint pains, pleural or pericardial effusions, photosensitive rash, hematuria or proteinuria, oral ulcers, SLE anemia, leukopenia or thrombocytopenia, seizures or psychosis, headache, fever, myalgias, autoantibodies Best screening test for SLE (most sensitive) ANA SLE-specific antibodies that correlate with level of disease Anti-dsDNA activity, nephritis and vasculitis SLE-specific antibodies with no clinical correlations Anti-Sm Antibodies associated with Sicca syndrome, subacute Anti-Ro (SS-A) cutaneous lupus, neonatal lupus with congestive heart block and decreased risk for nephritis Antibodies in drug-induced lupus Anti-Histone Antibodies predisposing to recurrent fetal loss, thrombosis, Anti-Phospholipid Antibody detected by ELISA for Cardiolipin and B2G1 and DRVVT Most serious manifestation of SLE Nephritis Immunosuppressive therapy for Class 3 to 5 lupus nephritis Steroids + Cyclophosphamide/Mycophenolate Mofetil Most common pulmonary manifestation of SLE Pleuritic with or without effusion Most frequent cardiac manifestation of SLE Pericarditis Fibrinous vegetations and endocarditis in SLE Libman-Sacks Endocarditis (LSE) Most frequent hematologic manifestation of SLE Normocytic Normochromic Anemia Most common manifestation of diffuse CNS lupus Cognitive Dysfunction Most common chronic dermatitis in SLE Discoid lupus erythematosus High-Yield Concepts in Rheumatoid Arthritis (RA) Most common form of chronic inflammatory arthritis Most common cardiac and valvular manifestation in RA Most common cause of death in patients with RA Environmental factor most implicated in RA Triad of neutropenia, splenomegaly and nodular RA Triad of keratoconjunctivitis sicca, xerostomia and RA Length of time for joint symptoms to be suggestive of RA Pathologic hallmarks of RA IgM against the Fc portion of IgG Serum marker with higher specificity for RA than RF Initial radiological finding in RA Test with greatest sensitivity for detecting synovitis, joint effusion and early bone and marrow changes in RA DMARD of choice for RA

RA Pericarditis and mitral regurgitation Cardiovascular disease Smoking Felty’s Syndrome Sjogren’s syndrome 6 weeks or more Synovial inflammation and proliferation, focal bone erosions, thinning of the articular cartilage and pannus formation Rheumatoid factor Anti-CCP Juxta-articular osteopenia (other findings: soft tissue swelling, symmetric joins space loss MRI Methotrexate


High-Yield Concepts in Osteoarthritis (OA) Obese, elderly, female complaining of unilateral knee pain exacerbated by exertion and relieved by rest and NSAIDs; no warmth, no swelling, nor redness; (+) crepitus Most common type of arthritis 2 major factors contributing to the development of OA Most potent risk factor for OA Nodes found on the PIP joint in OA Nodes found on the DIP joint in OA Fulcrum of the longest lever arm in the body Radiographic hallmarks of OA Initial analgesic of choice for OA High-Yield Concepts in Gouty Arthritis and Pseudogout 50 year old alcoholic male patient complaining of severe joint paint starting last night with noted swelling and redness on his right first metatarsophalangeal (MTP) joint Inflammation of the first MTP joint in gout Needle-shaped crystals that are negatively birefringent (yellow under parallel light and blue under perpendicular light) Rhomboid-shaped crystals that are weakly positively birefringent Mainstay of treatment during acute attack of gout

Indications for initiating urate-lowering therapy

Indications for uricosuric agents Most commonly used hypouricemic and best drug to use in urate overproducers, urate stone formers and renal disease Target therapeutic blood uric acid level for gout Joint most frequently affected in CPPD or pseudogout Radiograph findings of punctate or linear radiodense deposits in fibrocartilaginous joint menisci or articular hyaline cartilage suggestive of CPPD High-Yield Concepts in Psoriatic Arthritis Arthritis presenting with predominant DIP involvement, asymmetric or symmetric, involving one or more joints, dactylitis, shortening of digits and nail changes with or without silvery scaly skin lesions Nail changes in psoriasis/psoriatic arthritis

Uveitis in psoriatic arthritis 5 patters of psoriatic arthritis (from most to least common)

Radiographic characteristics of psoriatic arthritis Ideal treatment for psoriatic arthritis


OA Joint loading and joint vulnerability Age Bouchard’s nodes (Mnemonic: B of Bouchard comes first in the alphabet before H of Heberden’s) Heberden’s nodes Knee Asymmetric joint space narrowing, subchondral sclerosis and osteophytes Acetaminophen or Paracetamol

Gouty arthritis Podagra Gouty arthritis Pseudogout NSAIDs (Indomethacin) Conditions leading to overproduction (tumor lysis syndrome, tophi or chronic gouty arthritis, uric acid stones, serum uric acid >9 mg/dl or 535 mmol/l, repeated acute attacks of gouty arthritis, patient willingness to commit to long term therapy and not during acute attacks) Under excretors of uric acid (6.5%



ONCOLOGY High-Yield Concepts in Oncology Most significant risk factor for cancer overall Most common cancer worldwide Second most common cancer worldwide Most common cause of cancer death Growth involved in restraining cell growth and requiring both alleles to be mutated for tumorigenesis Genesis involved in cellular growth wherein mutation of one allele may lead to tumorigenesis Most effective means of treating cancer Deliver of radiation therapy from a distance Encapsulated sealed sources of radiation implanted directly or adjacent to tumor Radionuclides targeted to the site of the tumor Most significant risk factor for head and neck cancer Most commonly used treatment for head and neck cancers Most effective drugs against highly emetogenic agents

Age Lung cancer Breast cancer Lung cancer Tumor suppressor genes

Oncogenes Surgery Teletherapy

Brachytherapy Systemic radiation therapy Alcohol and smoking Chemoradiotherapy Serotonin receptor antagonists (i.e., ondansetron)

General Cancer Screening Recommendations for Asymptomatic Average-Risk Patients SCREENING PROCEDURE RECOMMENDED FREQUENCY Sigmoidoscopy Adults > 50 years old: screen every 5 years FOBT (fecal occult blood testing) Adults > 50 years old: screen every year Colonoscopy Adults > 50 years old: screen every 10 years Begin 3 yrs after first intercourse or by age 21 Pap smear Done yearly for standard pap smear and every 2 years for liquie-based test May screen every 2-3 years if last 3 tests are normal Women >65-70 years old may stop screening if no abnormal pap smears Mammography Women > 50 years old: screen annually (ACS) Women 50-74 years old: screen every 2 years (USPSTF) Men > 50 years old: screen annually DRE and PSA Men > 45 years old if African-American or with first degree relative 60% of esophageal circumference is infiltrated Diffuse type

Intestinal type Low socio-economic class, H. pylori infection, ingestion of high concentrations of nitrates in preserved foods, Menetrier’s disease (hypertrophy of rugal folds), blood group A Krukenberg tumor Sister Mary Joseph nodes Blumer’s nodes Virchow’s nodes Liver Complete surgical removal of the tumpr with resection of adjacent lymph nodes Stomach Eradication of H. pylori

Villous sessile adenomatous polyps, >2.5 cm in size FAP (familial adenomatous polyposis)


(polyposis coli) Multiple polyps in the small and large intestines with osteomas, fibromas and congenital hypertrophy of the retinal pigment epithelium Multiple polyps in the large intestine with brain tumors Multiple small and large intestinal polyps (hamaromatous/ juvenile), mucocutaneous pigmentation, tumors of the ovary, breast and pancreas Hereditary autosomal dominant predisposition to colon, ovarian and endometrial cancers caused by defects in DNA mismatch repair Most effective class of agents to reduce the risk of colon adenomas and carcinomas Usually non-obstructive, discovered late, with irondeficiency anemia Usually with obstructive symptoms and apple-core or napkin ring deformity on barium studies Hematochezia, tenesmus, narrowing of stool caliber Period of time when most recurrenecs after surgical resection of large bowel cancer occur Number of sampled lymph nodes necessary to accurately defin tumor stage during surgery Most frequent visceral site of metastasis for colon cancer Backbone chemotherapeutic agent for colon cancer and acts as a radiosensitizer for treatment of rectal cancer Major side effect of irinotecan used in FOLFIRI regimen for colon cancer Common side effect of oxaliplatin used in FOLFOX regimen for colon cancer

Gardner’s Syndrome Turcot’s Syndrome Peutz-Jeghers syndrome

Hereditary nonpolyposis colon cancer (Lynch syndrome) Aspirin and NSAIDs Right-sided colon cancers Left-sided colon cancers Rectosigmoid cancers Within the first 4 years Minimum of 12 lymph nodes Liver 5-fluorouracil (5-FU) Diarrhea Dose-dependent sensory neuropathy

High-Yield Concepts in Hepatic, Pancreatic and Biliary Malignancies Most common location of pancreatic cancer Pancreatic head Most common environmental risk factor for pancreatic Smoking cancer Most common physical sign in hepatocellular carcinoma Hepatomegaly (HCC) Non-cirrhotic or Child-Pugh A cirrhosis Candidates for resection in HCC Single lesion No metastasis Criteria for orthotopic liver transplant (Milan criteria) Single lesion < 5 cm or < 3 nodules each < 3 cm, no gross vascular invasion Variant of HCC associated with younger females, elevated Fibrolamellar HCC blood neurotensin levels, no cirrhosis Most common benign liver tumor among women Hemangioma Benign liver mass associated with contraceptive use, with Adenoma low potential for malignant change and risk of bleeding Benign liver mass with characteristic central scar, hypovascular on arterial phase and hypervascular on Focal nodular hyperplasia delayed phase CT Most useful diagnostic tool in differentiating between Triphasic CT scan benign and malignant liver masses Mucin-producing adenocarcinomas that arise from the bile ducts, majority of which are located in the hilar or central Cholangiocarcinoma area Nodular tumors arising at the bifurcation of the common bile Klatskin tumors duct Adenocarcnimoa arising within 2 cm of the distal end of the Ampullary carcinoma common bile duct


Palpable gallbladder associated with obstructive biliary malignancy Standard surgical procedure for pancreatic head and uncinate tumors High-Yield Concepts in Genitourinary Malignancies Most common site of malignancy in the urinary tract Most common source of gross hematuria Most common presentation of bladder, renal pelvis and ureteric cancer Vaccine component used as intravesicular therapy in bladder cancer Most common environmental risk factor for bladder and renal cell carcinoma Most common histopathologic type of renal carcinoma Classic triad of renal cell carcinoma Site where most prostate cancers develop Predominant therapy to reduce future risk of prostate cancer diagnosis PSA levels suggestive of cancer requiring biopsy

Test to establish prostate cancer diagnosis Scoring used to measure histologic aggressiveness of the dominant and secondary glandular histology of prostate cancers High-Yield Concepts in Soft Tissue Malignancies Most common site of metastasis of soft tissue sarcomas Mainstay of treatment for Ewing’s sarcoma, PNET and rhabdomyosarcoma Most common malignant tumor of bone Account for majority of bone sarcomas, predominant in young males, usually occurring on the metaphysis of long bones, distal femur, proximal tibia and humerus Radiographic hallmarks of osteosarcoma Most important prognostic factor for long-term survival in osteosarcoma Site most commonly involved in bone metastasis High-Yield Concepts on Skin Malignancies Lack of an endonuclease necessary for thymidine dimer repair  increased susceptibility to skin cancers of all types One or few small waxy, semitranslucent nodules forming around a central depression that may be ulcerated, crusted or bleeding, edge is rolled or pearly with rodent ulcer, rarely metastasizes Most common site of basal cell carcinoma Most common type of basal cell carcinoma Dome-shaped, elevated, hard infiltrating lesion (deeply nodular), may eventually develop an ulcer, occurs on sunexposed areas In situ form of squamous cell carcinoma

Courvoisier’s sign Pylorus preserving pancreaticduodenectomy Whipple’s procedure)


Urinary bladder Urinary bladder Painless hematuria BCG Smoking Clear cell carcinoma Hematuria Abdominal pain Flank or abdominal mass Peripheral zone 5-alpha reductase inhibitors (finasteride/dutasteride)  

Free PSA 0.15 ng/ml/cm 3 PSA levels >4 ng/ml with PSA velocity or rise of >0.75 ng/ml/year  Levels 0.5 ng/ml/year Transrectal ultrasound-guided needle biopsy Gleason scoring

Lungs Chemotherapy Plasma cell tumors Osteosarcoma Moth-eaten appearance Speculated periosteal reaction (sunburst appearance) Cuff of periosteal new bone formation (Codman’s triangle) Response to chemotherapy Vertebrae

Xeroderma pigmentosa

Basal cell carcinoma

Face/head and neck area Classical or nodular type Squamous cell carcinoma Bowen’s Disease


Major risk factor for squamous cell carcinoma of the skin Known precursor lesion of squamous cell carcinoma of the skin Most common type of melanoma Characteristics of a malignant lesion melanoma (versus benign nevus)

Single greatest determinant of metastasis of melanoma Single greatest risk factor for melanoma Most common type of melanoma in dark-skinned individuals and Asians Single most important prognostic factor for melanoma Most important determinant of outcome in melanoma Primary lesion of erythematous edematous evanescent rash Thickening of skin with accentuation of skin fold markings Loss of epidermis without loss of dermis Loss of both epidermis and dermis Common Paraneoplastic Syndromes PARANEOPLASTIC SYNDROME Hypercalcemia SIADH Cushing’s Syndrome Hypoglycemia from IGF-2 excess Erythrocytosis Trousseau’s Syndrome (migratory thrombophlebitis) Myasthenia gravis, pure red cell aplasia Lambert-Eaton myasthenic syndrome (LEMS)

Chronic lung term sun exposure Actinic keratosis Superficial spreading Asymmetry. Border irregularity, Color variegation, Diameter >6mm, ChangE in the lesion Depth of invasion (Breslow thickness) Personal history of melanoma Acral-lentiginous Melanoma Regional lymph node metastasis Early excision Wheal Lichenification Erosion Ulcer

ASSOCIATEED MALIGNANCY PTHrP: squamous cell carcinoma (lung, head & neck, skin, breast, GU, GI) Increased vitamin D: lymphomas Small cell carcinoma of the lung, carcinoid tumors, GI, GU, ovarian cancer Ectopic ACTH: small cell lung cancer, carcinoid, pancreatic islet cell tumors Mesenchymal tumors, hepatocellular and adrenal carcinomas Renal and hepatocellular cancer, cerebellar hemangioblastomas Pancreatic cancer Thymoma Small cell carcinoma of the lung

Common Chemotherapy Drugs: Actions and Adverse Effects ALKYLATING AGENTS (INTERCALATE DNA: NON-CELL-CYCLE SPECIFIC) Cyclophosphamide Alopecia, bone marrow toxicity, gonadal failure; Metabolized to acrolein  can cause hemorrhagic cystitis  give mesna (antidote) Cisplatin Ototoxicity, nephrotoxicity, neuropathy  give ammifostine (antidote) Busulfan Pulmonary fibrosis Nitroureas Neurotoxicity Oxaliplatin Neurotoxicity Procarbazine Disulfram-like reaction ANTITUMOR ANTIBIOTICS (INTERCALATE DNA; NON-CELL-CYCLE SPECIFIC) Bleomycin Pulmonary fibrosis Dactinomycin/Actinomycin D Myelosuppression Doxorubicin/Adriamycin Cardiotoxicity  give dexrazoxane (antidote) ANTIMETABOLITES (INTERFERE WITH DNA SYNTHESIS; S-PHASE SPECIFIC) Methotrexate Inhibits dihydrofolate reductase Myelosuppression  give leucovorin (antidote) 5-FU Inhibits thymidylate synthase Myelosuppression  give uridine (antidote) Azathioprine and 6Purine analogue Myelosuppression, increased toxicity with intake of Mercaptopurine (6-MP) allopurinol (because these drugs are metabolized


Cytarabine Hydroxyurea


Vinblastine and Vincristine

Etoposide, Teniposide Irinotecan, Topotecan

Pyrimidine analogue Inhibits ribonucleotide reducatse

by xanthine oxidase) Pancytopenia Myelosuppression, GI upset

MICROTUBULE INHIBITORS (M-PHASE SPECIFIC) Hyperstabilize polymerized microtubules preventing their Alopecia, hypersensitivity, myelosuppession break down during anaphase Vinblastine: myelosuppression (Mnemonic: “blast Attach to B tubulin and inhibit polymerization the bone marrow”) Vincristine: neurotoxicity TOPOISOMERASE INHIBITORS Inhibit topoisomerase II Alopecia, GI irritation, myelosuppession Inhibit topoisomera I Diarrhea, severe myelosuppression



DERMATOLOGY Erythematous Non-Scaly Papules Erythematous papules, pustules, cysts, nodules, open and closed comedones on the face, chest and upper back Primary lesion of acne Most important consideration before initiating isotretinoin (vitamin A) therapy for severe acne Erythematous pruritic or painful papules with central punctum Erythematous macules papules more pruritic at night located a the groin, axillae, webs of fingers, toes, elbows and wrists, other family members with similar lesions Imaginary circle intersecting site of involvement in scabies Slightly elevated tortuous lines in the skin with a vesicle or pustule at the end containing the mite Etiologic cause of scabies Intense pruritus of the scalp, posterior cervical lymphadenopathy, excoriations and erythematous papules at the nape of the neck and retriauricular area secondary impetigo, nits more common in retroarticular area, common in children Discrete extremely pruritic erythematous papulovesicles accompanied by prickling burning or tingling, frequently on the antecubital, popliteal, trunk and inframammary areas, common in hot humid climates Erythematous Non-Scaly Nodules Acute, round, tender, circumscribed, perifollicular, erythematous lesion that ends in central suppuration Refers to two or more confluent furuncles Refers to inflammation of the follicles resulting to erythematous papules that may eventually develop pustules Most common implicated causative agent for the diseases above Erythematous Non-Scaly Plaques Dark-red to purple skin discoloration, dusky with borders not clearly delineated, deeper tissue involvement, pain out of proportion to he physical findings, rapid progression of lesion, may have crepitus History of wound or blister, erythematous area with non-distinct borders, warm, edematous, painful, may have fever, central portion of lesion may become fluctuant and may rupture and discharge purulent material Most common portal of entry in the leg for cellulitis Erythematous plaque, heat, swelling, highly characteristic raised indurated border, fever, systemic symptoms Ill-defined hypopigmented macules and/or plaque, with minimal sensory loss to light touch and temperature, low AFB bacterial counts on skin biopsy Macules, papules, plaques and nodules, nerves are enlarged and tender, progressive loss of hair, high AFB bacterial counts, leonine facies Loss of eyebrows in leprosy High-Yield Concepts on Eczematous Dermatitis Erythematous greasy yellow brown scaling on scalp, eyebrows, ears and perinasal areas, dandruff, can spread beyond the hairline to the forehead Most common location of seborrheic dermatitis In infants yellow brown scaling on the scalp or seborrheic dermatitis of the scalp Organism implicated in seborrheic dermatitis Pruritic erythematous patches and plaques, scaling, lichenification, on the flexural, antecubital, popliteal areas in adults and in the face and extensors in infants and

Acne vulgaris Comedones (closed: whiteheads, open: blackheads  black due to oxidation) Rule out pregnancy (isotretinoin is extremely teratogenic) Insect bites Scabies Circle of Hebra Burrows Sarcoptes scabiei Pediculosis capitis Miliaria rubra or prickly heat (“bungang araw”)

Furuncle Carbuncle Folliculitis Staphylococcus aureus

Necrotizing fasciitis

Cellulitis Tinea pedis Erysipelas Tuberculoid leprosy, mild/early Borderline to lepromatous leprosy Madarosis

Seborrheic dermatitis Scalp presenting as dandruff Cradle cap Pityrosporum ovale Atopic dermatitis


children Linear transverse fold below edge of the lower eyelids Discrete coin-shaped erythematous, edematous vesicular and crusted patches on the lower extremities and extensor surfaces of the arms Dermatitis sudden in onset, no previous history or exposure, symptoms of pain and burning usually from acidic or alkali substances Most common site of involvement of Irritant Contact Dermatitis Eczematous eruption following exposure to a known or unknown allergen, usually appearing first at the site of contact, associated with plants, nickel and other compounds, can form patterns on the skin (i.e. lineal lesions with plant exposure) Most common cause of allergic contact dermatitis Papulosquamous Scaly Diseases Erythematous papule and plaques covered with silvery scales o elbows, knees, scalp, with nail pits and other nail changes Pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off in psoriasis Psoriasis involving the folds, recesses, and flexor areas such as axillae, groin, inframammary folds Abrupt eruption of psoriasis lesion following acute infection such as streptococcal pharyngitis Circular sharply circumscribed slightly erythematous dry scaly hypopigmented patches with advancing scaly border and central clearing producing annular outlines Most common fungal disease Causes majority of tinea pedis Infection of the nail plate Multiple scale hyper- or hypo-pigmented macules over the chest, back, abdomen and proximal extremities Etiologic cause of Tinea versicolor Classical microscopic finding in Tine versicolor of short, thick fungal hyphae and large numbers of variously sized spores Salmon-colored macules and papules, collarette of scaling, scales tend to fold along the long axis of stretch follows skin lines (hanging curtain or “christmas tree” sign), herald patch Sexually-Transmitted and Vesiculobullous Diseases Symmetrical, generalized, maculopapular eruptions, polymorphous, usually over the face, shoulders, flanks and pamls and soles with scaling, with suggestive sexual history, painless genital ulcer Popular lesions located on folds of moist skin usually around genitals and anus, may become hypertrophic, forming soft, red, mushroom-like mass, moist weeping gray surface Most frequent manifestation of orolabial herpes Dew drop on rose petal, teardrop on an erythematous base, starting with macules progressing to vesicles pustules and crusting, examination of lesions show different ages of healing usually starting on the trunk, spreading centripetally outward Most common complication of varicella Erythema, papules and plaques initially, mild pain a few days before, subsequently developing vesicles and blisters following a dermatomal distribution, painful Vesicles on the side and tip of nose, indicative of ophthalmic zoster Involvement of the facial and auditory nerves by varicella zoster virus Large tense blisters on flexor surfaces, groin axillae, and trunk, subepidermal blister, anti-hemidesmosome antibodies Papules, vesicles and pustules with honey-colored crusts Variant of impetigo, inadequately treated leading to punched out ulcerative lesions

Dennie-Morgan folds Nummular eczema Irritant contact dermatitis Hands Allergic contact dermatitis Exposure to plants

Psoriasis Auspitz sign Inverse psoriasis Guttate psoriasis Tinea Tinea pedis Trichophyton rubrum Onychomycosis Tine versicolor Malassezia furfur Spaghetti and meatballs

Pityriasis rosea

Secondary syphilis

Condylomata lata Fever, blister or cold sore Varicella Secondary bacterial infection Herpes zoster Hutchinson’s sign Ramsay-Hunt Syndrome Bullous pemphigoid Impetigo contagiosa Ecthyma


High-Yield Concepts on Drug-Induced or –Related Reactions Blisters, epidermal detachment resulting from epidermal necrosis, targer lesions, dusky purpuric macules with mucosal involvement, 30% involvement of body surface area 10-30% involvement of body surface area Drugs commonly associated with SJS-TEN Multiple erythematous plaques with target or iris lesion morphology, usually precipitated by recent new drug ingestion, often triggered by mycoplasma pneumonia and HSV Manual pressure to the skin may elicit separation of the epidermis (found in staphylococcal scalded skin syndrome, SJS, TEN and pemphigus vulgaris) Most common pattern of drug-induced reaction Other Important Skin Diseases and Terminologies Young children with individual lesions of smooth surfaced, firm, dome-shaped, pearly, fleshy papules with central umbilication Numerous small eosinophilic and basophilic inclusion bodies found in histology of molluscum contagiosum Brown-black plaques with adherent greasy scales, stuck on appearance Sudden appearance of multiple seborrheic keratoses suggestive of visceral and hematologic malignancy Erythematous macules and papules, macerated skin areas and satellite lesions, white friable patches on mucosal surfaces, immunocompromised states Increased thicknes of the stratum corneum Hyperkeratosis with retention of nuclei in stratum corneum Epidermal accumulation of edematous fluid in intracellular space Process referring to loss of cohesion between epidermal cells Violaceous flat-topped papules and plaques with gray lines (Wickham’s striae) Condition in dermatological diseases wherein traumatized areas tend to develop new lesions (found in verruca and psoriasis)

Steven Johnson’s Syndrome Toxic Epidermal Necrolysis (TEN) SJS-TEN Overlap Sulfa drugs, anticonvulsants, nevirapine, allopurinol, lamotrigine, oxicam NSAIDs Erythema multiforme Nikolsky’s sign Morbilliform or maculopapular

Molluscum contagiosum Henderson-Paterson bodies Seborrheic keratosis Sign of Leser Trelat Candida infection Hyperkeratosis Parakeratosis Spongiosis Acantholysis Lichen planus Koebner phenomenon



NEUROLOGY High-Yield Physiology Concepts in Neurology Found in various sites (e.g. ANS and NMJ), decreased in Huntington’s dementia and Alzheimer’s dementia Found in the locus ceruleus of the pons, for arousal/wakefulness Found in the substantial nigra, decreased in Parkinson’s Disease, increased in schizophrenia, for fine-tuning of movements Found in the median raphe of the brainstem, derived from tryptophan, converted to melatonin, involved in mood and sleep

Derivatives of phenylalanine

Found in the spinal interneurons, main inhibitory neurotransmitter Found in the brain, main inhibitory neurotransmitter, from glutamate Excitatory neurotransmitter in the CNS Output pathway from reward and punishment centers, lesions here will produce anterograde amnesia Helps search memory storehouses, lesions here will produce retrograde amnesia Waves in the EEG of alert, sleeping and relaxed individuals, respectively High-Yield Physiology Concepts Relating to Cranial Nerves Cranial nerve for opening of eyelids, contraction of most EOMs, accommodation and pupillary constriction (miosis) Cranial nerve for special sensation (taste) of the anterior 2/3 of the tongue Cranial nerve for general sensation (e.g. pain) of the anterior 2/3 of the tongue Cranial nerve for facial msucles Cranial nerve for facial sensation and muscles of mastication

Acetylcholine (Ach) Norepinephrine (NE) Dopamine Serotonin Mnemonic: “Pare, True Love Does Not Exist To Me”: Phenylalanine  Tyrosine  L-Dopa  Dopamine  Norepinephrine  Epinephrine (Thyroxine and Melanin from Tyrosine) Glycine GABA Glutamate Hippocampus Thalamus Beta waves, Alpha waves, Delta waves

CN III (Oculomotor nerve) CN VII (Facial nerve) CN V (Trigeminal nerve) CN VII (Facial nerve) CN V (Trigeminal nerve)

High-Yield Physiology Concepts Relating to the Autonomous Nervous System Mydriasis, sweating, increased HR, bronchodilation, GU and GI contraction, uterine Sympathetic effects relaxation and contraction, vasodilation of the skeletal muscles, vasoconstriction of the skin and GI tract, ejaculation Mnemonic: “PLASMA” Parasympathetic, Long Pre-Ganglionic Tract, Ach used (pre-synaptic), Short PostParasympathetic Nervous System Ganglionic Tract, Muscarinic Receptors, Ach used (post-synaptic) Alpha-1 (for smooth muscle contraction in sphincters, radial muscles of the iris, vasoconstriction) Adrenergic Receptors Alpha-2 (in pre-synaptic terminals), Beta-1 (heart and kidney), Beta-2 (for smooth muscle relaxation in bronchiolar muscles, uterus, vasodilation)


DISEASES OF THE NERVOUS SYSTEM High-Yield Concepts Related to Headaches Highly characteristic of posterior fossa brain tumors Dominant symptom in temporal (giant cell) arteritis Most common primary hadache syndromes Key pathway for pain in migraine Most disabling headache Mainstays of pharmacologic therapy in migraine Most important factor in selection of the optimal regimen for a migraine patient Most effective drug classes in the treatment of migraine Most efficacious of the triptans Core feature of cluster headache Most satisfactory treatment in cluster headache Most serious cause of secondary headache Classic headache associated with brain tumor High-Yield Concepts Related to CNS Tumors Preferred diagnostic test for any patient suspected of having a brain tumor, and should be performed with gadolinium contrast administration The only test necessary to diagnose a brain tumor Glucocorticoid of choice for brain tumors because of ts relatively low mineralocorticoid activity The only established risk factors for primary brain tumors Most common primary brain tumor of childhood Most common primary brain tumor overall Frequently plays an important role in the pathogenesis of HIV-related primary CNS lymphoma Most common malignant brain tumor of childhood Most common malignant brain tumor overall Meningiomas are most commonly located over the Main differential diagnosis of meningioma Most common schwannomas Most common site of brain metastases 85% of all brain metastases are Most common sources of brain metastases Malignancy with greatest propensity for brain metastasis, found in 80% of patients at autopsy Malignancies with propensity to metastasize to the dura and can mimic meningioma Arises in prostate and breast cancer, which have strong propensity to metastasize to axial skeleton Brain metastases are best visualized on ___ where they appear as well-circumscribed lesions Cancers with greatest propensity to bleed Most common cause of a hemorrhagic metastasis Most common among hematologic malignancies to metastasize to the subarachnoid space Solid tumors that most frequently cause leptomeningeal metastases

Vomiting that precedes headache Headache Migraine, tension-type headache and cluster headache Trigeminovascular input from the meningeal vessels Migraine Judicious use of one or more drugs that are effective in migraine Severity of the attack Anti-inflammatory agents 5-HT1B/1D receptor agonists (triptans), and dopamine receptor antagonists Rizatriptan and eletriptan Periodicity Administration of drugs to prevent cluster attacks until the bout is over Subarachnoid hemorrhage Most evident in the morning and improves during the day

Cranial MRI Neuroimaging Dexamethasone Exposure to ionizing radiation: meningiomas, gliomas, schwannomas Immunosuppression: primary CNS lymphoma Grade I astrocytomas: pilocytic astrocytomas (WHO grade I) Meningiomas Epstein-Barr Virus (EBV) Medulloblastomas Grade IV astrocytoma (Glioblastoma) Cerebral convexities Dural metastasis Vestibular schwannomas or acoustic neuromas Gray matter-white matter junction Suprenetorial Lung and breast cancer Melanoma Prostate and breast cancer Spinal cord compression MRI Melanoma, thyroid, kidney cancer Lung cancer Acute leukemia Breast and lung carcinomas and melanoma


Definitive method and often considered the gold standard to diagmose leptomeningeal metastases CSF cytologic examination is most useful in Part of the spine affected most commonly in epidural metastases Presenting symptom of epidural metastasis in virtually all patients Best test for epidural metastasis Surgical procedure of choice for epidural metastasis Standard treatment for brain metastases Most serious toxicity from radiotherapy as they are often irreversible Complication seen most commonly after WBRT Second only to myelosuppression as dose-limiting toxicity of chemotherapeutic agents

Demonstration of tumor cells in CSF Hematologic malignancies Thoracic spine, followed by the lumbar and then cervical spine Back pain MRI of the complete spine Complete removal of the mass, typically anterior to the spinal canal Whole-Brain Radiotherapy (WBRT) Late delayed toxicity Leukoencephalopathy Neurotoxicity

High-Yield Concepts in CNS Infections

First task in the approach to CNS infection

Encephalitis Classic clinical triad of meningitis Classic clinical triad of brain abscess Cerebritis Pathognomonic sign of meningeal irritation and is present when neck resists passive flexion Most common form of suppurative CNS infection Most common cause of meningitis in adults >20 years Important clue to diagnosis of meningococcal infection Most disastrous complication of increased ICP Most common etiologic organisms of community-acquired bacterial meningitis Most important agents in acute viral meningitis Most common symptom of brain abscess Optimal therapy for brain abscess

High-Yield Concepts Related to Seizures Paroxysmal event due to abnormal excessive or synchronous neuronal activity in the brain Condition where a person has recurrent seizures die to underlying causes not associated with structural brain damage

Triad of Lennox-Gastaut Syndrome

Highest incidence of seizures First clue of typical absence seizures

Electrophysiologic hallmark of typical absence seizures Main seizure type in 10% of all persons with epilepsy

Identify whether an infection predominantly involves the subarachnoid space (meningitis) or whether there is evidence of either generalized or focal involvement of brain tissue in the cerebral hemispheres, cerebellum or brainstem Brain tissue is directly injured by a viral infection Fever, headaches and nucal rigidity Headache, fever, focal neurologic deficit (present in
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