MBBS Differential List

May 25, 2016 | Author: Rex-Anne Jesse Bobb | Category: Types, School Work
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MBBS differentials...


Loren Warmington

Causes of Clubbing Respiratory  Cancer - Bronchogenic Ca -Lung Mets -Pleural Mesothelioma - Oseophageal cancer  COPD  Tuberculosis  Suppurative Lung Disease - Lung Abscess - Empyema - Bronchiectasis  Cystic Fibrosis  Interstitial Lung disease - Sarcoidosis - Fibrosing alveolitis - Asbestosis etc.  Pulmonary AV fistuala Cardiovascular  Congenital Cyanotic Heart disease - Tetralogy of Fallot (ToF) - Coarctation of aorta - Pulmonary stenosis (critical)  Subacute Bacterial endocarditis  Eisenmenger’s syndrome  Left Atrial myxoma  Isolated Toe clubbing - PDA with Shunt reversal - Called Eisenmenger PDA Abdomen  Liver Cirrhosis  Neoplasm - Colorectal Ca - Gastric Ca - GI lymphoma - Hepatoma  Inflammatory BD - Crohn’s Disease - Ulcerative colitis  Malabsorption - Celiac disease - Whipple’s disease - Cystic Fibrosis - Intestinal Polyposis Other  Hyperthyroidism - Particularly Graves  Idiopathic

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Thymoma Thalassemia

Causes of Hepatomegaly Infection  Viral -Hepatitis - EBV  Bacterial -Weil’s disease (leptospiro.) - Syphilis  Parasitic -Hydatid cyst -Schistosomiasis, -Amoebic abscess, - Malaria - Leishmaniasis Malignancy  Hepatocellular carcinoma  Metastases – GI, Lung, breast and melanomas Hematologic  Myeloproliferative -Myelofibrosis -CML  Lymphoma -Hodgkin’s - Non-Hodgkin’s  Leukaemia -ALL -AML  Sickle cell -Hepatic sequestration -Extramedullary haematopoiesis Hepatic congestion  Cardiac failure  Hepatic vein thrombosis Storage disorders  Wilson’s  Haemochromatosis  Gaucher’s Infiltrative  Sarcoidosis  Amyloidosis Biliary obstruction; e.g. Pancreatic Ca Fatty Liver (NASH) Early cirrhosis Whipple’s disease Causes of Pulsatile liver  Tricuspid regurgitation Causes of Tender Hepatomegaly


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Hepatitis Rapid liver enlargement o Rt heart failure o Budd-Chiari Syndrome o Hepatoma Causes of Splenomegaly Infection  Bacterial – Subacute bacterial endocarditis  Viral - CMV, EBV  Parasite - Malaria Haematological  Lymphoproliferative - Lymphoma - Chronic LL  Myeloproliferative disease - Myelofibrosis -Chronic ML -Polycythemia vera -Essential thrombo.  Thalassemia  Sickle cell Vascular congestion  Cirrhosis  Hepatic vein obstruction Connective Tissue  RA, SLE Storage disorders  Gaucher’s disease  Niemann-Pick disease Infiltrative  Amyloidosis  Sarcoidosis Causes of Massive Splenomegaly (>8cm) Infection  Visceral Leishmaniasis (Kala-azar)  Malaria  Schistosomiasis Haematologic  Myeloproliferative - CML, Myelofibrosis  Sickle cell -Splenic Sequestration in the young, HbSC disease

Loren Warmington

Bacterial - IE, Tb, Syphilis  Fungal - Histoplasmosis  Protozoal -Toxoplasmosis, - Filariasis - Leishmaniasis Malignancy o Leukaemia -ALL, CLL o Lymphoma -Hodgkin’s, NonHodgkin’s Metastatic Solid Tumour Connective Tissue Disease  RA, SLE Drugs - Phenytoin, hydrallazine, - allopurinol Other - Sarcoidosis Localized Lynphadenopahy 

Storage Disorder o Gaucher’s  Idiopathic Tropical (Africa & South-East Asia) Causes of Moderate Splenomegaly (4 -8 cm) Lymphoproliferative disorders  Hodgkins disease  Chronic lymphoytic leukemia, Cirrhosis with portal hypertension Causes of Hepatsplenomealy List is essentially the same as splenomegaly alone. Common causes include - Chronic leukemias - Lymphoproliferative disorders - Cirrhosis with portal HTN - Myelofibrosis Causes of Palpable Kidneys  Thin individual  AD Polycystic kidney disease  Maligancy - Renal Cell Cancer - Wilm’s Tumour (Nephroblastoma)  Hydronephrosis (Can be bilateral rarely)  Renal Cyst / Abscess  Amyloidosis (Can be bilateral rarely)  Hypertrophy of a single functioning kidney  Nephropathy o HIV o Sickle cell o Diabetes Iliac Fossa Renal Transplant (May have cushinoid features 2nd to steroids Generalized Lymphadenopathy Infection  Viral -HIV, Ebstein Barr virus, CMV, Measles, Mumps, Rubella, Viral Hepatitis,

Causes of Ascites Portal (SAAG > 1.1g/dL)  Exudative (Protein > 2.5g/L) o Budd-Chiari o CCF  Transudative (Protein < 2.5g/dL) o Cirrhosis o Hepatic failure Non-Portal (SAAG < 1.1g/dL)  Exudative (Protein > 2.5g/dL) o Intraabdominal malignancy o Intraabdominal infection e.g. Tb o Pancreatitis  Transudative (Protein < 2.5g/dL) o Nephrotic Syndrome o Protein-losing enteropathy o Severe malnutrition with anasarca Causes of Local Edema inflammation /infection


venous or lymphatic obstruction  thrombophlebitis  chronic lymphangitis  resection of regional lymph nodes  filariasis Some Causes of Generalized Edema Increased hydrostatic pressure Increased fluid retention  Cardiac causes e.g. CHF  Hepatic causes e.g. cirrhosis  Renal causes e.g. acute and  chronic renal failure Vasodilators (especially CCBs) Refeeding edema Decreased oncotic pressure Hypoalbuminemia Hormonal  hypothyroidism  exogenous steroids  pregnancy  estrogen Causes of Jaundice Unconjugated Prehepatic  Hemolytic anemia - Sickle Cell Anemia - Hereditary Spherocytosis - Hereditary Elliptocytosis  Gilbert’s syndome  Hematoma resorption Conjugated Hepatic  Viral – Hepatits A B, C  Leptospirosis  Hepatic Abscess Post Hepatic  Choledocholithiasis  Ascending Cholangitis  Sclerosing cholangitis  Pancreatits

Loren Warmington

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Cancer at head of Pancreas or Ampule Methastatic cancer Foreign body in CBD eg. worm

Causes of Tachpnea/SOB Cardiovascular  acute MI  CHF/LV failure  aortic stenosis  mitral stenosis  elevated pulmonary venous pressure Respiratory Airway disease  asthma  COPD exacerbation  upper airway obstruction (foreign body, mucus plugging, anaphylaxis) Parenchymal lung disease  ARDS  pneumonia  interstitial lung disease Pulmonary vascular dis.  PE  pulmonary HTN  pulmonary vasculitis Pleural disease  pneumothorax  pleural effusion Neuromuscular and chest wall disorders  C-spine injury  polymyositis, myasthenia gravis, Guillain-Barri syndrome  kyphoscoliosis Anxiety/psychosomatic Severe anemia Causes of Cough Airway Irritants  Inhaled smoke, dusts, fumes  Aspiration astric contents (GERD)  Oral secretion  Foreign body

 Postnasal drip Airway Disease  URTI including postnasal drip and sinusitis  Acute or chronic bronchitis  Bronchiectasis  Neoplasm  External compression by node or mass lesion  Asthma  COPD Parenchymal Disease  Pneumonia  Lung abscess  Interstitial lung disease  CHF Drug-induced (e.g. ACE inhibitor) Differentials of Hemoptysis Airway Disease  Acute or chronic bronchitis  Bronchiectasis  Bronchogenic CA  Bronchial carcinoid tumour Parenchymal Disease  Pneumonia  TB  Lung abscess Miscellaneous:  Goodpasture’s syndrome  Idiopathic pulmonary hemosiderosis Vascular Disease  PE  Elevated pulmonary venous pressure: LVF Mitral stenosis  Vascular malformation Miscellaneous  Impaired coagulation  Pulmonary endometriosis

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diagnosis is made by location and patient’s age anterior compartment (sternum to anterior border of pericardium) more likely to be malignant o 5 Ts – Thymoma Thyroid enlargement (goiter) Teratoma Thoracic aortic aneurysm Tumours (lymphoma, parathyroid, esophageal, angiomatous) o lymphoma, lipoma, pericardial cyst middle compartment (anterior to posterior pericardium) o pericardial cyst, bronchogenic cyst/tumour, lymphoma, lymph node enlargement, aortic aneurysm posterior compartment (posterior pericardium to vertebral column) o neurogenic tumours, meningocele, enteric cysts, lymphomas, diaphragmatic hernias, esophageal tumour, aortic aneurysm

Mediastinal Mass

Signs and Symptoms

Etiology and Pathophysiology


50% asymptomatic (most of these are benign); when symptomatic, 50% are malignant

Loren Warmington

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chest pain, cough, dyspnea, recurrent respiratory infections hoarseness, dysphagia, Horner’s syndrome, facial/upper extremity edema (SVC compression) paraneoplastic syndromes (e.g. myasthenia gravis (thymomas))

Investigations  

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CXR (compare to previous) CT with contrast (provides information regarding anatomic location, density, relation to mediastinal vascular structures) MRI – specifically indicated in the evaluation of neurogenic tumours ultrasound (best for assessment of structures in close proximity to the heart and pericardium) radionuclide scanning – 131I (for thyroid), Gallium (for lymphoma) biochemical studies – thyroid function, serum calcium, phosphate, parathyroid hormones, AFP, beta-hCG biopsy (mediastinoscopy, percutaneous needle aspiration)

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Bronchogenic Cancer Pathological Classification 

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Management  

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depends on the diagnosis decide if the lesion should be excised (most isolated benign masses should be removed) needle aspiration of suspected benign cystic lesion resection via minimally invasive video assisted

procedures (bronchogenic cysts, localized neurogenic tumours) exploration via sternotomy or thoracotomy diagnostic biopsy rather than major operation if mass is likely to be a lymphoma, germ cell tumour, or unresectable invasive malignancy ± post-op radiotherapy/chemothera py if malignant

bronchogenic cancer (90% of primary lung cancers) (for characteristics, see Table 24 below) o classified into small cell lung cancer (SCLC) and non-SCLC (NSCLC i.e. adenocarcinoma, squamous cell, large cell), bronchioalvelolar cancer (BAC) o incidence of adenocarcinoma is increasing lymphoma secondary metastases: breast, colon, prostate, kidney, thyroid, stomach, cervix, rectum, testes, bone, melanoma

Risk Factors   

cigarette smoking: 85% of lung cancer related to smoking asbestos 5x increased risk, asbestos + smoker 80-90x increased risk radiation: radon, uranium (especially if smoker)


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arsenic, chromium, nickel genetic damage parenchymal scarring: granulomatous disease, fibrosis, scleroderma passive exposure to cigarette smoke air pollution: exact role is uncertain HIV

Signs and Symptoms       

cough (75%); beware of chronic cough that changes in character dyspnea (60%) chest pain (45%) hemoptysis (35%) other pain (25%) clubbing (21%) constitutional signs: anorexia, weight loss, fever, anemia

Presentation by Location of Tumour Extension 

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lung, hilum, mediastinum, pleura: pleural effusion, atelectasis, wheezing pericardium: pericarditis, pericardial tamponade esophageal compression: dysphagia phrenic nerve: paralyzed diaphragm recurrent laryngeal nerve: hoarseness superior vena cava syndrome: obstruction of SVC causing neck and facial swelling, as well as dyspnea and cough o other symptoms associated with SVC compression: hoarseness, tongue swelling, epistaxis, and hemoptysis o physical findings include dilated neck veins, increased number

Loren Warmington

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of collateral veins covering the anterior chest wall, cyanosis, edema of the face, arms, and chest, Pemberton’s sign o milder symptoms if obstruction is above the azygos vein lung apex (Pancoast tumour): Horner’s syndrome, brachial plexus palsy, most commonly C8 and T1 nerve roots rib and vertebrae: erosion distant metastasis to brain, bone, liver, adrenals paraneoplastic syndromes o a group of disorders associated with malignant disease, not related to the physical effects of the tumour itself o most often associated with SCLC

Investigations 

initial diagnosis o imaging: CXR, CT chest + upper abdomen, PET scan, bone scan o cytology: sputum o biopsy: bronchoscopy, percutaneous, mediastinoscopy staging work-up o blood work: LFTs, calcium, ALP o imaging: CXR, CT thorax and abdomen, bone


scan, neuroimaging invasive: bronchoscopy, mediastinoscopy, mediastinotomy, thoracotomy

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Therapy for Bronchogenic Cancer 

chemotherapy (no role for chemo alone, only in combination with other treatments) o cisplatin and etoposide o paclitaxel, vinorelbine, and gemcitabine are new NSCLC therapies o new biologics, e.g. epidermal growth factor inhibitor (Gefitinib) o complications:  acute: tumour lysis syndrome, infection, bleeding, myelosupp ression, hemorrhag ic cystitis (cyclophos phamide), cardiotoxic ity (doxorubici n), renal toxicity (cisplatin), peripheral neuropath y (vincristine )  chronic: neurologic damage, leukemia, second primary neoplasms


radiotherapy surgery o only chance for cure is resection when tumour is still localized o contraindications if any evidence of local extension or metastases  patients with surgically resectable disease must undergo m ediastinal node sampling since CT thorax is not accurate in 20-40% of cases  poor pulmonary status (i.e. unable to tolerate resection of lung) palliative care for endstage disease

Pleural Effusion Light's criteria - a pleural effusion is likely exudative if at least one of the following exists: 1. The ratio of pleural fluid protein to serum protein is greater than 0.5 2. The ratio of pleural fluid LDH and serum LDH is greater than 0.6 3. Pleural fluid LDH is greater than 2/3 times the normal upper limit for serum Transudative Pleural Effusions

Loren Warmington

Pathophysiology: alteration of systemic factors that affect the formation and absorption of pleural fluid (i.e. increased capillary hydrostatic pressure, decreased plasma oncotic pressure)

etiology     

congestive heart failure cirrhosis nephrotic syndrome pulmonary embolism (may cause transudative or exudative effusion) peritoneal dialysis, hypothyroidism, CF, urinothorax

Exudative Pleural Effusions

Pathophysiology: increased permeability of pleural capillaries or lymphatic dysfunction etiology 

infectious o parapneumonic effusion (associated with bacterial pneumonia, lung abscess o empyema (bacterial, fungal, TB), TB pleuritis, viral infection malignancy lung carcinoma (35%) o lymphoma (10%) o metastases: breast (25%), ovary, kidney  mesothelio ma vascular/cardiac o collagen vascular diseases: RA, SLE o

pulmonary embolism, after coronary artery bypass surgery intra-abdominal o subphrenic abscess o esophageal perforation (elevated pleural fluid amylase) o pancreatic disease (elevated pleural fluid amylase) o Meig’s syndrome (ascites and hydrothorax associated with an ovarian fibroma or other pelvic tumour trauma o chylothorax: occurs when the thoracic duct is disrupted and chyle accumulates in the pleural space, due to trauma, tumour o hemothorax: due to rupture of a blood vessel, commonly by trauma or tumours other o pneumothorax (spontaneous, traumatic, tension) o pleural thickening (chronic infection, neoplasm, inflammatory) o

Appearance of Fluid Bloody - trauma, malignancy White - chylothorax, empyema Black - aspergillosis, amoebic liver abscess Yellow-green - rheumatoid pleurisy Viscous - malignant


mesothelioma Ammonia odour urinothorax Food particles - esophageal rupture Analysis of Pleural Effusion  Protein, LDH transudate vs. exudate  Gram stain, Ziehl-Nielsen stain (TB), culture looking for specific organisms  Cell count differential neutrophils vs. lymphocytes (lymphocytic TB, lymphoma)  Cytology - malignancy, infection  Glucose (low) RA, TB, empyema, malignancy, esophageal rupture  Rheumatoid factor, ANA, complement - collagen vascular disease  Amylase - pancreatitis, esophageal perforation, malignancy  pH - empyema CHF & pulmonary HTN Symptoms Dyspnea, PND, orthopnea, palpitations, peripheral edema Physical Exam

Loren Warmington

Displaced, hyperdynamic apex (LV dilataton), +/left parasternal lift (LAE with MR), apical thrill Auscultation: holosystolic murmur at apex, radiating to axilla (also sometimes to base or back if jet is directed posteriorly) +/- mid-diastolic rumble (often no MS), S1 normal or soft, loud S2 (if pulmonary HTN), S3 usually present. Severity gauged by LVD, S3, diastolic flow rumble. Investigations ECG: LAE, left atrial delay (bifid P waves), +/- LVH CXR: LVH, LAE, pulmonary venous HTN Echo: severity of MR, (LV function - EF, ↑LA/LV), (leaflets – flail, vegetations etc.) Card. Cath: Assess coronaries, assess flow and contours in LA, Prominent LA V wave on Swan-Ganz Treatment Asymptomatic: serial Echos, IE prophylaxis. Symptomatic: decrease preload (diuretics)and decrease afterload (ACEIs) for severe MR & poor surgical candidate; stabilize acute MR with vasodilators b/f surgery Surgery if: acute MR with CHF, papillary muscle rupture, NYHA class III-IV CHF, AFib, LVEF 75% of pts with MR & myxomatous MV disease (MVP). Annuloplasty rings, leaflet

repair, chordae transfers/shorten/replace ment Valve replacement: failure of repair, heavily calcified annulus Advantage of Repair: low rate of endocarditis, no anticoagulation, less chance of re-operation Causes of Aortic Incompetence Ring  Left ventricular dilatation  HTN Valve  RHD  IE  Bicuspid aortic valve Root  Marfan’s  Syphilitic Aortitis  Aortic dissection  Takayasu’s aortitis Ankylosing spondylitis, seronegative arthritides RA, SLE Trauma Aortic Incompetence

Etiology Supravalvular: Aortic root disease (Marfan’s, atherosclerosis & dissecting aneurysm, connective tissue disease) Valvular: Congenital (bicuspid AV, large VSD), IE Acute Onset: IE, aortic dissection, trauma, failed prosthetic valve


Pathophysiology Volume overload => LV dilatation => increased SV, high sBP & low dBP => increased wall tension => pressure overload => LVH (low dBP => decreased coronary perfusion) Symptoms (Usually only becomes symptomatic late in disease when LV failure develops) Dyspnea, orthopnea, PND, syncope, angina. Physical Exam Waterhammer pulse, bisferiens pulse, Difference in femoralbrachial systolic BP > 20 (Hill’s test wide pulse pressure) hyperdynamic apex, displaced PMI, heaving apex Auscultation: early decrescendo diastolic murmur at LLSB (cusp –See this more due to RHD) or RLSB (aortic root), best heard sitting, leaning forward, on full expiration. Soft S1, absent S2, S3 (late) Investigations ECG: LVH, LAE CXR: LVH, LAE, aortic root dilatation Echo/TTE: Gold standard. Quantify AR, leaflet or aortic root anomalies. Visualize regurge into LV. Radionuclide scan: Sensitive to decreased LV function (EF doesn’t increase w/ exercise Cath: if >40 yrs and surgical candidate - to assess for ischemic heart disease Exercise testing: hypotension with exercise

Loren Warmington

Treatment Asymptomatic: serial Echos, afterload reduction (ACEIs if normal LV function) Symptomatic: avoid exertion, treat CHF Surgery if: NYHA class IIIIV CHF, LVEF < 50% with/without symptoms, increasing LV size Surgical Options Valve replacement:Most Cases. Valve types include mechanical, bioprosthetic, homograph and sometimes pulmonary autograph Valve repair: limited role. repair of valves to improve coaptation Aortic root replace (Bentall proced.):when ascending aortic aneurysm present, valved conduit used Other Signs in Aortic Regurge Large-volume, 'collapsing' pulse also known as: Watson's water hammer pulse Corrigan's pulse (rapid upstroke and collapse of the carotid artery pulse) low diastolic and increased pulse pressure de Musset's sign (head nodding in time with the heart beat) Quincke's sign (pulsation of the capillary bed in the nail) Traube's sign (systolic and diastolic murmurs described as 'pistol shots' heard over the femoral artery when it is gradually compressed) Duroziez's sign (a double sound heard over the femoral artery when it is compressed distally)

Müller's sign (pulsations of uvula) Austin Flint murmur, a soft mid-diastolic rumble heard at the apical area. It appears when regurgitant jet from the severe aortic insufficiency renders partial closure of the anterior mitral leaflet. Mitral Stenosis

Etiology Rheumatic disease most common cause; Lung carcinoid, Mitral annular calcification, Lupus. Congenital rarely Pathophysiology MS => fixed CO & Left atiral enlargement => increased LA pressure => pulmonary vascular resistance & CHF; worse with Afib (no atrial kick), tachycardia (decreased atrial emptying time) & pregnancy (increased preload) Symptoms SOBOE, orthopnea, fatigue, palpitations, peripheral edema, malar flush (Pulm. Htn), pinched and blue facies (severe MS). Hemoptysis (late). If TR or RVF then hepatic enlargement/pulsatility, ascites, peripheral edema. Physical Exam Irregular pulse if AFib ( no A wave on JVP), left parasternal lift, palpable diastolic thrill at apex (tapping apex –not displaced) Auscultation: mid-


diastolic rumble at apex, best with bell in LLD position following exertion, No radiation. Loud S1 (valves not pliable), OS following loud P2 (heard best during expiration). Crackles. If pulm. Htn present look for loud /palpable P2, Pulmonary Regurge (Graham Steell murmur). It may also be associated with MR and TR. Long murmur & short A2Opening snap interval correlate with worse MS Investigations ECG: Normal S rhythm/AFib, LAE (P mitrale), RVH, RAD CXR: L atrial enlargement (LA appendage, double contour, carina splaying) Pulmonary Congestion (Kerley B lines), MV calcification, Flattened left heart border. Echo/TTE: Thickened calcified valve, fused leaflets, LAE, PAP, TR Cath: concurrent CAD if >40 yrs (male) or >50 yrs (female) Treatment Avoid exertion, fever (increased LA pressure), treat AFib (rate control, cardioversion) and CHF, increase diastolic filling time (beta-blockers, digitalis). IE prophylaxis? Anticoagulation – previous embolus. Surgery if: NYHA class IIIIV CHF, failure of medical therapy (usually MVA unicuspid valve), calcification (wear and tear), rheumatic disease Pathophysiology Outflow obstruction => increased EDP => concentric LVH => LV failure => concentric CHF, subendocardial ischemia Symptoms “Triad” of Exertional angina, syncope (fixed CO or arrythmias) and dyspnea. PND, orthopnea, peripheral edema

Physical Exam Narrow pulse pressure, brachial-radial delay, pulsus parvus et tardus, sustained PMI Auscultation: crescendodecrescendo Systolic ejection murmur radiating to R clavicle & carotid (may have thrill at neck), musical quality at apex (Gallavardin phenomenon), thrill in 2nd RICS, S4 (early in disease), soft S2 w/paradoxical splitting, S3 (late) Complications: Recurrent PE, pulmonary infections – pneumonia and bronchitis, LA thrombus (Systemic embolic to kidney, brain, spleen, arm) Investigations ECG: LVH & strain, LBBB, LAE, AFib CXR: post-stenotic aortic root dilatation, calcified valve, LVH, LAE, CHF (later) ECHO: Test of choice. Reduced valve area (RVA) pressure gradient (PG), LVH, reduced LV function Card Cath: Rule out CAD before surgery esp. with cases of angina. Also in inconclusive ECHO - PG, RVA Treatment Asymptomatic: Serial Echos, avoid exertion ?IE prophylaxis Symptomatic: avoid nitrates/arterial dilators & ACEIs in severe AS


Surgery if: symptomatic, LV dysfunction or in moderate AS when other cardiac surgery is done Surgical Options Valve replacement : Procedure of choice. aortic rheumatic valve disease & trileaflet valve Open/Balloon valvuloplasty: Repair may be possible in children. Rarely done in adults – Temporizing in Pregnancy, patient stabilization or as palliative if people with comordities. Tricuspid Regurg  RHD  I.E. (esp in IV drug abuse)  Pulm HTN  

Carcinoid syndrome Rt ventricular failure

Tricuspid Regurge

Etiology RV dilatation, IE (IV drug use), rheumatic disease, congenital (Ebstein anomaly), carcinoid Pathophysiology RV dilatation => TR => further RV dilatation => right heart failure Symptoms Peripheral edema, fatigue, palpitations Physical Exam

Loren Warmington

Large V waves in JVP (“CV”, +ve abdomino jugular reflux, Kussmaul’s sign (↑JVP with inspiration), holosystolic murmur at LLSB accentuated by inspiration, left parasternal lift, hepatomegaly +/- systolic pulsations, edema, ascites Investigations ECG: RAE, RVH, AFib CXR: RAE, RV enlargement Echo: diagnostic Treatment Preload reduction (diuretics) Surgery if: usually only if other surgery needed (e.g. MVR)

Prominent A waves in JVP, +ve abdominojugular reflex, Kussmaul’s sign, diastolic rumble 4th left intercostals space Investigations ECG: RAE CXR: dilatation of RA without pulmonary artery enlargement Echo: diagnostic Treatment Preload reduction (diuretics) Surgery if: usually only if other surgery needed (e.g. MVR) Surgical Options: Commissurotomy Valve Replace: if severely diseased valve. Bioprosthesis preferred Pulmonary Stenosis

Surgical Options Annuloplasty, i.e. repair (rarely replacement) Tricuspid Stenosis Etiology Usually congenital, rheumatic disease (rare), carcinoid Etiology Rheumatic disease, congenital, carcinoid, fibroelastosis; usually accompanied by MS Pathophysiology Increased RA pressure => right heart failure => decreased CO and fixed on exertion Symptoms Peripheral edema, fatigue, palpitations Physical Exam

Pathophysiology Increased RV pressure => RV hypertrophy => right heart failure Symptoms Chest pain, syncope, fatigue, peripheral edema Physical Exam Systolic murmur at 2nd LICS accentuated by inspiration, pulmonary ejection click, right-sided S4 Investigations ECG: RVH CXR: prominent pulmonary arteries


enlarged RV echo: diagnostic Treatment Balloon valvuloplasty if severe symptoms Surgical Options Percutaneous or open balloon valvuloplasty Pulmonary Regurge

Etiology Pulmonary HTN, IE, rheumatic disease, tetrology of Fallot, postrepair Pathophysiology Increased RV volume => increased wall tension => RV hypertrophy => right heart failure Symptoms Chest pain, syncope, fatigue, peripheral edema Physical Exam Early diastolic murmur at LLSB, Graham Steell (diastolic) murmur 2nd and 3rd LICS increasing with inspiration Investigations ECG: RVH CXR: prominent pulmonary arteries if pulmonary HTN; enlarged RV echo: diagnostic Treatment Rarely requires treatment; valve replacement if severe Surgical Options

Loren Warmington

Pulmonary valve replacement

None unless symptomatic and significant MR o

Mitral Valve Prolapse Etiology Myxomatous degeneration of chordae; thick, bulky leaflets that crowd orifice; Marfan’s syndrome; pectus excavatum, straight back syndrome, other MSK abnormalities; R shunt and therefore are not cyanotic but the RVOTO is progressive, resulting in increasing R>L shunting with hypoxemia and cyanosis history: hypoxic spells primary pathophysiology is hypoxia, leading to increased pulmonary vascular resistance (PVR) and decreased systemic resistance, occurring in exertional states (e.g. crying, exercise) paroxysm of rapid and deep breathing, irritability and crying hyperpnea, increasing cyanosis often leading to deep sleep and decreased intensity of murmur (decreased flow across RVOTO) peak incidence at 2-4 months of age o if severe may lead to seizures, loss of

Surgical Options


consciousness, death (rare) management: O2, knee-chest position, fluid bolus, morphine sulfate, propanolol

physical exam: single loud S2 due to severe pulmonary stenosis (i.e RVOTO) investigations:  

ECG: RAD, RVH CXR: boot shaped heart (small PA, RVH), decreased pulmonary vasculature, right aortic arch (in 20%)

treatment: surgical repair within first two years of life, or earlier if marked cyanosis, spells, or severe RV outflow tract obstruction Ventricular Septal Defect (VSD) most common congenital heart defect (30-50% of CHD) Small VSD (majority)  

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history: asymptomatic, normal growth and development physical exam: early systolic to holosystolic murmur, best heard at left lower sternal border (LLSB) investigations: ECG and CXR are normal treatment: most close spontaneously, do not need surgical closure even if remains patent

Moderate-to-large VSD

Loren Warmington

natural history: secondary pulmonary hypertension, CHF by 2 months of age history: delayed growth and development, decreased exercise tolerance, recurrent URTIs or “asthma” episodes, CHF physical exam: holosystolic murmur at LLSB with thrill, middiastolic rumble at apex, size of VSD is inversely related to intensity of murmur investigations: o ECG: left ventricular hypertrophy (LVH), left atrial hypertrophy (LAH), RVH o CXR: increased pulmonary vasculature, cardiomegaly, CHF treatment: treatment of CHF and surgical closure by 1 year of age

Patent Ductus Arteriosus (PDA)  

patent vessel between descending aorta and left pulmonary artery epidemiology o functional closure within first 15 hours of life, anatomical closure within first days of life o 5-10% of all congenital heart defects o common in premature infants (1/3 of infants 50 mmHg o exercise restriction required

Pulmonary Stenosis (Children)  

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valvular (90%), subvalvular, or supravalvular usually part of other congenital heart lesions (e.g. Tetralogy of Fallot) or in association with other syndromes (e.g. congenital rubella, Noonan syndrome) critical pulmonic stenosis: inadequate pulmonary blood flow, dependent on ductus for oxygenation, progressive hypoxia and cyanosis history: spectrum from asymptomatic to CHF physical exam: wide split S2 on expiration, SEM at ULSB, pulmonary ejection click investigations: o ECG: RVH o CXR: dilated poststenotic pulmonary artery treatment: surgical repair if critically ill or severe PS, or if presence of symptoms in older infants/children

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systemic venous return re-enters systemic circulation directly most prominent feature is cyanosis (O2 sat 1 major areas of functioning (work, interpersonal relations, selfcare) markedly below the level achieved prior to the onset of symptoms C. continuous signs of disturbance for >6 months, including >1 month of active phase symptoms; may include prodromal or residual phases

paranoid o preoccupation with one or more delusions (typically persecutory or grandiose) or frequent auditory hallucinations o relative preservation of cognitive functioning and affect; onset tends to be later in life; believed to have the best prognosis catatonic o at least two of: motor immobility (catalepsy or stupor); excessive motor activity (purposeless, not influenced by external stimuli); extreme negativism (resistance to instructions/attem pts to be moved) or mutism; peculiar voluntary movement (posturing, stereotyped movements, prominent


mannerisms); echolalia (repeating words/phrases of another’s speech) or echopraxia (imitative repetition of another’s movements, gestures or posture) disorganized o disorganized speech and behaviour; flat or inappropriate affect o poor premorbid personality, early and insidious onset, and continuous course without significant remissions undifferentiated o symptoms of criteria A met, but does not fall into the 3 previous subtypes residual o absence of prominent delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behaviour o continuing evidence of disturbance indicated by the presence of negative symptoms or two or more symptoms in criteria A present in attenuated form

Good Prognositic Factors

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Acute onset Precipitating factors Good cognitive functioning Good premorbid functioning No family history Presence of affective symptoms Absence of structural brain abnormalities Good response to drugs Good support system Etiology - multifactorial: disorder is a result of interaction between both biological and environmental factors 

genetic 50% concordance in monozygotic (MZ) twins; 40% if both parents have schizophrenia; 10% of dizygotic (DZ) twins, siblings, children affected neurochemistry dopamine hypothesis theory: excess activity in the mesolimbic dopamine pathway may mediate the positive symptoms of psychosis (i.e. delusions, hallucinations, disorganized speech and behaviour, and agitation) neuroanatomy decreased frontal lobe function, asymmetric temporal/limbic function, decreased basal ganglia function; subtle changes in thalamus, cortex, corpus callosum, and ventricles; cytoarchitectural abnormalities neuroendocrinology – abnormal growth hormone, prolactin, cortisol, and adrenocorticotropic hormone neuropsychology – global defects seen in attention, language, and memory suggest lack of

connectivity of neural networks indirect evidence of geographical variance, winter season of birth, and prenatal viral exposure

Brief Psychotic Episode 

Management of Schizophrenia 

pharmacological o acute treatment and maintenance with antipsychotics ± anticonvulsants ± anxiolytics o management of side effects psychosocial o psychotherapy (individual, family, group): supportive, cognitive behavioural therapy (CBT) o assertive community treatment (ACT) o social skills training, employment programs, disability benefits o housing (group home, boarding home, transitional home)

Schizophreniform Disorder 

 

diagnosis: criteria A, D & E of schizophrenia are met; an episode of the disorder lasts at least 1 month but less than 6 months treatment: similar to acute schizophrenia prognosis: better than schizophrenia; begins and ends more abruptly; good pre- and postmorbid function


diagnosis: acute psychosis (presence of 1 or more positive symptoms in criteria A14 of schizophrenia) lasting from 1 day to 1 month, with eventual full return to premorbid level of functioning can occur after a stressful event or postpartum (see Postpartum Mood Disorders) treatment: secure environment, antipsychotics, anxiolytics prognosis: good, selflimiting, should return to pre-morbid function in about 1 month

DSM-IV-TR Diagnostic Criteria for Schizoaffective Disorder A. uninterrupted period of illness during which there is either a major depressive episode (MDE), manic episode, or a mixed episode concurrent with symptoms meeting criteria A for schizophrenia B. in the same period, delusions or hallucinations for at least 2 weeks in the absence of prominent mood symptoms C. symptoms that meet criteria for a mood episode are present for a substantial portion of total duration of active and residual periods of the illness D. the disturbance is not due to the direct physiological effects of a substance or GMC 

treatment: antipsychotics, mood

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stabilizers, antidepressants prognosis: between that of schizophrenia and that of mood disorder

DSM-IV-TR Diagnostic Criteria for Delusional Disorder A. non-bizarre delusions for at least 1 month B. criterion A for schizophrenia has never been met (though patient may have tactile or olfactory hallucinations if they are related to the delusional theme) C. functioning not markedly impaired; behaviour not obviously odd or bizarre D. if mood episodes occur concurrently with delusions, total duration has been brief relative to duration of the delusional periods E. the disturbance is not due to the direct physiological effects of a substance or GMC 

subtypes: erotomanic, grandiose, jealous, persecutory, somatic, mixed, unspecified treatment: psychotherapy, antipsychotics, antidepressants prognosis: chronic, unremitting course but high level of functioning

Folstein Mini Mental State Exam (MMSE) to assess Dementia: Orientation (time and place) – 5 points Memory (immediate and delayed recall) – 5 points Attention and Concentration

Language (comprehension, reading, writing, repetition, naming) Spacial ability (intersecting pentagons) Gross screen for cognitive dysfunction: Total score is out of 30; 80 mg of diazepam o delirium tremens, recurrent arrhythmias, or multiple seizures o medically ill or unsafe to discharge home

Wernicke-Korsakoff Syndrome 

 

alcohol-induced amnestic disorders due to thiamine deficiency necrotic lesions – mammillary bodies, thalamus, brain stem Wernicke’s encephalopathy (acute and reversible): triad of nystagmus (CN VI palsy), ataxia and confusion Korsakoff’s syndrome (chronic and only 20% reversible with treatment): anterograde amnesia

and confabulations; cannot occur during an acute delirium or dementia and must persist beyond usual duration of intoxication/withdraw al management o Wernicke’s : thiamine 100 mg PO OD x 12 weeks o Korsakoff’s : thiamine 100 mg PO bid/tid x 3-12 mon

Prognosis    

relapse is common and should not be viewed as failure monitor regularly for signs of relapse 25-30% of abusers exhibit spontaneous improvement over 1 year 60-70% of individuals with jobs and families have an improved quality of life 1 year posttreatment

 

elation, euphoria, pressured speech, restlessness, sympathetic stimulation (i.e. tachycardia, mydriasis, sweating) prolonged use may result in paranoia and psychosis

medical emergency: hypertension, tachycardia, tonic-clonic seizures, dyspnea, and ventricular arrhythmias treatment with IV diazepam to control


initial crash (1-48 hrs): increased sleep, increased appetite withdrawal (1-10 wks): dysphoric mood plus fatigue, irritability, vivid, unpleasant dreams, insomnia or hypersomnia, psychomotor agitation or retardation complications: relapse, suicide (significant increase in suicide during withdrawal period) management: supportive management

Treatment of Chronic Abuse  

Overdose 


Cocaine Intoxication 

seizures and propanolol or labetalol to manage hypertension and arrhythmias

optimal treatment not established psychotherapy, group therapy, and behaviour modification useful in maintaining abstinence studies of dopamine agonists to block cravings show inconsistent results

Complications   

cardiovascular: arrhythmias, MI, CVA, ruptured AA neurologic: seizures psychiatric: psychosis, paranoia, delirium, suicidal ideation

Ganja  marijuana is the most often used illicit drug  psychoactive substance delta-9tetrahydrocannabinol (9THC)

Loren Warmington

 smoking is the most common mode of selfadministration  intoxication characterized by tachycardia, conjunctival vascular engorgement, dry mouth, increased appetite, increased sense of wellbeing, euphoria/laughter, muscle relaxation, impaired performance on psychomotor tasks including driving  high doses can cause depersonalization, paranoia, and anxiety  may trigger psychosis and schizophrenia in predisposed individuals  chronic use associated with tolerance and an apathetic, amotivational state  cessation does not produce significant withdrawal phenomenon  treatment of dependence includes behavioural and psychological interventions to maintain an abstinent state Medical Uses of Ganja Anorexia-cachexia (AIDS, cancer) Spasticity, muscle spasms (multiple sclerosis, spinal cord injury) Levodopa-induced dyskinesia (Parkinson's Disease) Controlling tics and obsessive-compulsive behaviour (Tourette's syndrome) Reducing intra-ocular pressure (glaucoma) Mood Disorders Mood disorders are defined by the presence of mood episodes 

mood episodes represent a combination of symptoms comprising a predominant mood state that is abnormal in

quality or duration; examples include: major depressive, manic, mixed, hypomanic types of mood disorders include: o depressive (major depressive disorder, dysthymia) o bipolar (bipolar I/II disorder, cyclothymia) o secondary to GMC, substances, medications

Medical Workup of Mood Disorder 

Secondary Causes of Mood Disorders 

 

   

infectious: encephalitis/meningitis, hepatitis, pneumonia, TB, syphilis endocrine: hypothyroidism, hyperthyroidism, hypopituitarism, SIADH metabolic: porphyria, Wilson’s disease, diabetes vitamin disorders: Wernicke’s, beriberi, pellagra, pernicious anemia collagen vascular diseases: SLE, polyarteritis nodosa neoplastic: pancreatic cancer, carcinoid, pheochromocytoma cardiovascular: cardiomyopathy, CHF, MI, CVA neurologic: Huntington’s disease, multiple sclerosis, tuberous sclerosis, degenerative (vascular, Alzheimer’s) drugs: antihypertensives, antiparkinsonian, hormones, steroids, antituberculous, interferon, antineoplastic medications


routine screening: o physical examination o complete blood count o thyroid function test o electrolytes o urinalysis, urine drug screen addtional screening: o neurological consultation o chest x-ray o electrocardiogram o

CT scan

Risk Factors for Depression    

   

sex: female > male age: onset in 25-50 year age group family history: depression, alcohol abuse, sociopathy childhood experiences: loss of parent before age 11, negative home environment (abuse, neglect) personality: insecure, dependent, obsessional recent stressors (illness, financial, legal) postpartum 5 of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either 1) depressed mood, or 2) loss of interest or

Loren Warmington

   

 

pleasure (anhedonia) Note: Do not include symptoms that are clearly due to a general medical condition, or mood-incongruent delusions or hallucinations depressed mood most of the day, nearly every day, as indicated by either subjective report or observation made by others markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day significant weight loss when not dieting or weight gain, or decrease or increase in appetite nearly every day insomnia or hypersomnia nearly every day psychomotor agitation or retardation nearly every day fatigue or loss of energy nearly every day feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely selfreproach or guilt about being sick) diminished ability to think or concentrate, or indecisiveness, nearly every day recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide B. the symptoms do not meet criteria for a Mixed Episode C. the symptoms cause clinically significant distress or impairment in social, occupational, or

other important areas of functioning D. the symptoms are not due to the direct physiological effects of a substance or a GMC E. the symptoms are not better accounted for by bereavement, i.e. after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation

Criteria for Depression (>5): MSIGECAPS

B. the Major Depressive Episode is not better accounted for by Schizoaffective Disorder and is not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder not otherwise specified C. there has never been a Manic Episode, a Mixed Episode, or a Hypomanic Episode. Note: This exclusion does not apply if all of the manic-like, mixedlike, or hypomanic-like episodes are substance- or treatment-induced or are due to the direct physiological effects of a general medical condition

M - Depressed Mood S - Increased/decreased Sleep I - Decreased Interest G - Guilt E - Decreased Energy C - Decreased Concentration A - Increased/decreased Appetite P - Psychomotor agitation/retardation S - Suicidal ideation



DSM-IV-TR Diagnostic Criteria for Major Depressive Disorder (MMD), Single Episode (vs. Recurrent) A. presence of a single Major Depressive Episode (vs. Recurrent, which requires presence of two or more Major Depressive Episodes; to be considered separate episodes, there must be an interval of at least 2 consecutive months in which criteria are not met for a MDE)


  

 

psychotic with hallucinations or delusions chronic - lasting 2 years or more catatonic - at least two of: motor immobility; excessive motor activity; extreme negativism or mutism; peculiarities of voluntary movement; echolalia or echopraxia melancholic - quality of mood is distinctly depressed, mood is worse in the morning, early morning awakening, marked weight loss, excessive guilt, psychomotor retardation atypical - increased sleep, weight gain, leaden paralysis, rejection hypersensitivity postpartum seasonal - pattern of onset at the same time each year (most often in the fall or winter)

Loren Warmington


magnetic stimulation, vagal nerve stimulation

biological  

genetic: 65-75% MZ twins; 14-19% DZ twins neurotransmitter dysfunction at level of synapse (decreased activity of serotonin, norepinephrine, dopamine) secondary to general medical condition

psychosocial   

psychodynamic (e.g. low self-esteem) cognitive (e.g. negative thinking) environmental factors (e.g. job loss, diet (omega 3 fatty acids), bereavement, history of abuse) co-morbid psychiatric diagnoses (e.g. anxiety, substance abuse, mental retardation, dementia, eating disorder)

Treatment 

 

biological: antidepressants, lithium, antipsychotics, anxiolytics, electroconvulsive therapy (ECT), light therapy psychological o individual therapy: psychodynamic, interpersonal, cognitive behavioural therapy o family therapy o group therapy social: vocational rehabilitation, social skills training experimental: deep brain stimulation, transcranial

DSM-IV-TR Criteria for Manic Episode 

A. a distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting >1 week (or any duration if hospitalization is necessary) B. during the period of mood disturbance, >3 of the following symptoms have persisted (4 if the mood is only irritable) and have been present to a significant degree: o inflated selfesteem or grandiosity o decreased need for sleep (e.g. feels rested after only 3 hours of sleep) o more talkative than usual or pressure to keep talking o flight of ideas or subjective experience that thoughts are racing o distractibility (i.e. attention too easily drawn to unimportant or irrelevant external stimuli) o increase in goaldirected activity (either socially, at work or school, or sexually) or psychomotor agitation o excessive involvement in pleasurable activities that have a high potential for


 

painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments) C. the symptoms do not meet criteria for a Mixed Episode (see below) D. the mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features E. the symptoms are not due to the direct physiological effects of a substance (e.g. drug of abuse, medication, or other treatment) or a general medical condition (e.g. hyperthyroidism). Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g. medication, electroconvulsive therapy, light therapy) should not count toward a diagnosis of Bipolar I Disorder

Criteria for Mania (>3): GST PAID Grandiosity Sleep (decreased need) Talkative Pleasurable activities, Painful consequences Activity Ideas (flight of) Distractable Mixed Episode

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criterion met for both manic episode and major depressive episode (MDE) nearly every day for 1 week criteria D and E of manic episodes are met

Risk Factors  

slight increase in upper socioeconomic groups 60-65% of bipolar patients have family history of major mood disorders

Hypomanic Episode   

Treatment criterion A of a manic episode is met, but duration is >4 days criterion B and E of manic episodes are met episode associated with an uncharacteristic decline in functioning that is observable by others change in function is not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization absence of psychotic features


Bipolar I Disorder o disorder in which at least one manic or mixed episode has occurred o commonly accompanied by at least 1 MDE but not required for diagnosis Bipolar II Disorder o disorder in which there is at least 1 MDE and at least 1 hypomanic episode o no past manic or mixed episode

biological: mood stabilizers, anticonvulsants, antipsychotics, antidepressants, ECT (Note: Treatment of bipolar depression must be done extremely cautiously, as a switch from depression to mania can result. Monotherapy with antidepressants should be avoided) psychological: supportive and psychodynamic psychotherapy, cognitive or behavioural therapy social: vocational rehabilitation, leave of absence from school/work, drug and EtOH cessation, substitute decision maker for finances, sleep hygiene, social skills training, education for family members

  

Differential Diagnosis 

Anxiety Disorders Anxiety is a universal human characteristic involving tension, apprehension, or even terror, which serves as an adaptive mechanism to warn about an external threat by activating the sympathetic nervous system (fight or flight) 

manifestations of anxiety can be described along a continuum of physiology, psychology, and behaviour


physiology - main brain structure involved is the amygdala; neurotransmitters involved include serotonin, cholecystokinin, epinephrine, norepinephrine, dopamine psychology one’s perception of a given situation is distorted which causes one to believe it is threatening in some way behaviour - once feeling threatened, one responds by escaping or facing the situation, thereby causing a disruption in daily functioning anxiety becomes pathological when fear is greatly out of proportion to risk/severity of threat response continues beyond existence of threat or becomes generalized to other similar/dissimilar situations social or occupational functioning is impaired

  

endocrine: hyperthyroidism, pheochromocytoma, hypoglycemia, hyperadrenalism, hyperparathyroidism CVS: congestive heart failure, pulmonary embolus, arrhythmia, mitral valve prolapse respiratory: asthma, pneumonia, hyperventilation metabolic: vitamin B12 deficiency, porphyria neurologic: neoplasm, vestibular dysfunction, encephalitis

Loren Warmington

substance-induced: intoxication (caffeine, amphetamines, cocaine), withdrawal (benzodiazepines, alcohol)

Medical Workup of Anxiety Disorder 

routine screening: physical examination, CBC, thyroid function test, electrolytes, urinalysis, urine drug screening additional screening: neurological consultation, chest x-ray, electrocardiogram (ECG), CT scan

(6) sleep disturbance (difficulty falling or staying asleep, or restless unsatisfying sleep)

D. the focus of the anxiety and worry is not confined to features of an Axis I disorder, such as panic disorder, social phobia, etc. E. the anxiety, worry, or physical symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

DSM-IV-TR Diagnostic Criteria for Generalized Anxiety Disorder A. excessive anxiety and worry (apprehensive expectation), occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance)

F. the disturbance is not due to the direct physiological effects of a substance or a GMC and does not occur exclusively during a Mood Disorder, a Psychotic Disorder, or a Pervasive Developmental Disorder

B. the person finds it difficult to control the worry


C. the anxiety and worry are associated with >3 of the following 6 symptoms (with at least some symptoms present for more days than not for the past 6 months). Note: Only one item is required in children     

(1) restlessness or feeling keyed up or on edge (2) being easily fatigued (3) difficulty concentrating or mind going blank (4) irritability (5) muscle tension

  

psychotherapy, relaxation, mindfulness, and CBT caffeine and EtOH avoidance, sleep hygiene pharmacotherapy: o benzodiazepin es (short term, low dose, regular schedule, long half-life, no prn) o buspirone (tid dosing) o others: SSRIs/SNRI, TCAs, betablockers combinations of above


DSM-IV-TR Diagnostic Criteria for PostTraumatic Stress Disorder A. the person has been exposed to a traumatic event in which both of the following were present: 

(1) the person experienced, witnessed, or was confronted with an event or events that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others (2) the person's response involved intense fear, helplessness, or horror. Note: In children, this may be expressed instead by disorganized or agitated behaviour

B. the traumatic event is persistently reexperienced in one (or more) of the following ways: 

(1) recurrent and intrusive distressing recollections of the event, including images, thoughts, or perceptions. Note: In young children, repetitive play may occur in which themes or aspects of the trauma are expressed (2) recurrent distressing dreams of the event. Note: In children, there may be frightening dreams without recognizable content (3) acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback

Loren Warmington

episodes, including those that occur on awakening or when intoxicated) Note: In young children, trauma-specific reenactment may occur (4) intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event (5) physiological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event

present before the trauma), as indicated by >2 of the following:     

(1) difficulty falling or staying asleep (2) irritability or outbursts of anger (3) difficulty concentrating (4) hypervigilance (5) exaggerated startle response

E. duration of the disturbance (symptoms in Criteria B, C, and D) is >1 month

DSM-IV-TR Diagnostic Criteria for Panic Disorder without Agoraphobia A - Both 1 and 2 (1) recurrent unexpected panic attacks: a discrete period of intense fear or discomfort, in which >4 of the following symptoms develop abruptly and reach a peak within 10 minutes    

C. persistent avoidance of stimuli associated with the trauma and numbing of general responsiveness (not present before the trauma), as indicated by three (or more) of the following:

F. the disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning


    

(1) efforts to avoid thoughts, feelings, or conversations associated with the trauma (2) efforts to avoid activities, places, or people that arouse recollections of the trauma (3) inability to recall an important aspect of the trauma (4) markedly diminished interest or participation in significant activities (5) feeling of detachment or estrangement from others (6) restricted range of affect (e.g. unable to have loving feelings) (7) sense of a foreshortened future (e.g. does not expect to have a career, marriage, children, or a normal life span)

D. persistent symptoms of increased arousal (not

CBT - systematic desensitization, relaxation techniques, thought stopping pharmacotherapy o SSRIs o benzodiazepines (for acute anxiety) o first-line adjunct – atypical antipsychotics (quetiapine, olanzapine, risperidone) EMDR (eye movement desensitization and reprocessing): an experimental method of reprocessing memories of distressing events by recounting them while using a form of dual attention stimulation such as eye movements, bilateral sound, or bilateral tactile stimulation


  

  

palpitations, pounding heart, or accelerated heart rate sweating trembling or shaking sensations of shortness of breath or smothering feeling of choking chest pain or discomfort nausea or abdominal distress feeling dizzy, unsteady, lightheaded, or faint derealization (feelings of unreality) or depersonalization (being detached from oneself) fear of losing control or going crazy fear of dying paresthesias (numbness or tingling sensations), chills or hot flushes

(2) at least one of the attacks has been followed by 1 month (or more) of >1 of the following:  

persistent concern about having additional attacks worry about the implications of the attack or its consequences (e.g. losing control, having a heart attack, "going crazy") a significant change in behavior related to the attacks

Loren Warmington

B. absence of agoraphobia C. the panic attacks are not due to the direct physiological effects of a substance or GMC D. the panic attacks are not better accounted for by another mental disorder, such as Social Phobia, Specific Phobia, ObsessiveCompulsive Disorder, PostTraumatic Stress Disorder, Separation Anxiety Disorder Treatment 

supportive psychotherapy, relaxation techniques (visualization, boxbreathing), cognitive behavioural therapy (correct distorted thinking, desensitization/exposure therapy) pharmacotherapy o benzodiazepines (short term, low dose, regular schedule, long half-life, no prn) o SSRIs/SNRI (start low, go slow, aim high since anxiety patients are very sensitive) o other antidepressants (Trazodone, Remeronâ, MAOIs; avoid Wellbutrina)

Panic Disorder with Agoraphobia Agoraphobia - anxiety about being in places or situations from which escape might be difficult (or embarrassing) or where help may not be available in the event of having an unexpected panic attack

fears commonly involve situations: being out alone, being in a crowd, standing in a line, or travelling on a bus situations are avoided, endured with anxiety or panic, or require companion treatment: as per panic disorder

Criteria for Panic Disorder (>4): "STUDENTS FEAR the 3 Cs" Sweating Trembling Unsteadiness, dizziness Depersonalization, Derealization Excessive heart rate, palpitations Nausea Tingling Shortness of breath Fear of dying, losing control, going crazy 3 C's: Chest pain, Chills, Choking Suicide Risk Factors Epidemiologic factors 

    

age: increases after age 14; second most common cause of death for ages 15-24; highest rates in persons >65 years sex: male race/ethnic background: white or native Canadians on reserves marital status: widowed/divorced living situation: alone; no children 60% chance for child; two parents >80% chance for child frequently affects infants, children, and young adults females only slightly more at risk than males

inflammation, lichenification, excoriations are secondary to relentless scratching atopic palms: prominent palmar creases associated with o keratosis pilaris (hyperkeratosis of hair follicles, “chicken skin”) o xerosis o occupational hand dryness patients usually suffer from three flares per year

Distribution   

infant (onset at 2-6 months old): face, scalp, extensor surfaces childhood (>18 months): flexural surfaces adult: hands, feet, flexures, neck, eyelids, forehead, face, wrists


no prerequisite investigations to diagnose atopic dermatitis may consider: skin biopsy, immunoglobulin serum levels (often elevated serum IgE level), patch testing, and skin prick tests to look for contact or environmental allergies

majority of cases are mild and easily managed goal: reduce signs and symptoms, prevent or reduce recurrences, and provide long-term management to prevent progression from early disease to full AD flare treatment maximized (i.e. less flare-ups, modified course of disease) if diagnosis made early and treatment plan individualized o individualized based on age, severity, sites and extent of involvement, presence of infection, previous responses to therapy reassure patients that although there is no absolute cure, the disease can be controlled avoid triggers of AD: irritants (detergents and solvents, certain clothing, water hardness), inappropriate bathing habits (long hot showers), microbes (S. aureus), stress, sweating, contact allergens, and

Loren Warmington

environmental aeroallergens (dust mites) enhance barrier function of the skin o simplest and most important aspect of controlling AD o involves regular application of moisturizers +/diluted corticosteroid wet-wrap dressings  emollients hydrate the skin and reduce pruritus o twice daily application is recommended even in absence of symptoms, especially after bathing or swimming  bathing promotes hydration when followed by the application of moisturize rs to the skin consider psychological support for some patients

Anti-inflammatory therapies 

a) topical corticosteroids: o effective, rapid symptomatic relief for acute flares o different formulations and potencies suitable for nearly any area of skin

best applied immediately after bathing o control inflammation with a potent topical steroid; prescribe a milder one following resolution of acute flare o systemic immunosuppressi on may be needed in severe cases o flares may respond to systemic antistaphylococcal therapy side effects:  skin atrophy, purpura, striae, steroid acne, perioral dermatitis, and glaucoma when used around the eyes b) topical immunomodulators o long-term management o calcineurin inhibitors such as pimecrolimus (Elidelâ„¢) and tacrolimus (Protopicâ„¢)  block calcineurin and inhibit inflammat ory cytokine transcripti on in activated T-cells and other inflammat ory cells o




significant adverse events may include skin burning and transient irritation advantages of long-term management of AD over long-term corticosteroid use:  rapid, sustained effect in controlling pruritus  produce no skin atrophy  safe for the face and neck  no significant systemic toxicities associated with their use

Prognosis 

50% clear by age 13, few persist >30 years of age

Complications 

infections are common: diagnose early and treat appropriately (i.e. antibiotic, antifungal, antiviral therapy); infections must be resolved before applying antiinflammatory treatments o topical mupirocin or fusidic acid is

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often sufficient oral antibiotics (i.e. cloxacillin, cephalexin) for widespread S. aureus infections

Seborrheic Dermatitis Greasy, erythematous, yellow, non-pruritic scaling papules and plaques; occurs in areas rich in sebaceous glands Etiology 

possible etiologic association with Pityrosporum ovale (yeast)

Epidemiology   

common in infants and at puberty increased incidence in immunocompromised patients e.g. HIV in adults, can cause dandruff (pityriasis sicca)

 

face: Nizoral cream OD + mild steroid cream OD or bid scalp: salicylic acid in olive oil or DermaSmoothe FS lotion (peanut oil, mineral oil, fluocinolone acetonide 0.01%) to remove dense scales, 2% ketoconazole shampoo (Nizorale), ciclopirox (Stieprox ) shampoo, selenium sulfide (e.g. Selsun) or zinc pyrithione (e.g. Head and Shoulders) shampoo, steroid lotion (e.g. betamethasone valerate 0.1% lotion bid)

HTLV Associated Dermatitis  

Signs and Symptoms

 

 

infants - one cause of cradle cap children may be generalized with flexural and scalp involvement adults - diffuse in areas of scalp margin with yellow to white flakes, pruritus, and underlying erythema sites: scalp, eyebrows, eyelashes, beard, face, trunk, body folds, genitalia face: eyebrows, sides of nose, posterior ears, glabella chest: over sternum


 

The average age of onset is 2 years. The skin manifestations become less severe with age. Severe exudative dermatitis of the scalp, external ear, retroauricular areas, eyelid margins, paranasal skin, neck, axillae and groins Generalized fine papular rash Chronic watery nasal discharge sometimes with crusting HTLV-1 seropositivity Staphylococcus aureus and/or Bhaemolytic streptococci commonly cultured from anterior nares and skin Responds to antibiotics but relapses if antibiotics withdrawn

Lichen Planus


acute or chronic inflammation of mucous membranes or skin characterized by violaceous papules, especially on flexural surfaces

Epidemiology  

association with hepatitis C may be triggered by severe emotional stress

Signs and Symptoms 

 

  

small, polygonal, flattopped, shiny, violet papules; resolves with hyperpigmented macules Wickham’s striae: greyish lines over surface; pathognomonic sites: wrists, ankles, mucous membranes in 60% (mouth, vulva, glans), nails, scalp mucous membrane lesions: lacy, whitish reticular network, milkywhite plaques/papules; increased risk of SCC in erosions and ulcers nails: longitudinal ridging; dystrophic scalp: scarring alopecia spontaneously resolves in weeks or lasts for years (mouth and shin lesions) Koebner phenomenon: develops in areas of trauma

Treatment 

 

topical corticosteroids with occlusion or intradermal steroid injections short courses of oral prednisone (rarely) photochemotherapy for generalized or resistant cases

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oral retinoids for erosive lichen planus in mouth


Secondary syphilis can present with a non-pruritic papulosquamous eruption but usually ALSO has palmar lesions.

Pityriasis Rosea Definition and Clinical Features 

 

 

acute, self-limiting, erythematous eruption characterized by red, oval plaques/patches with central scales that do not extend to edge of lesion sites: trunk, proximal aspects of arms and legs long axis of lesions follows parallel to ribs producing “Christmas tree” pattern on back varied degree of pruritus most start with a “herald” patch which precedes other lesions by 1-2 weeks

Psoriasis 

Mnemonic PSORIASIS: Pathophysiology Pink papules/Plaques/Pinpoint bleeding (Auspitz sign)/Physical injury (Koebner phenomenon) Silver scale/Sharp margins Onycholysis/Oil spots Rete Ridges with Regular elongation Itching Arthritis/Abscess (Monro)/Autoimmune Stratum corneum with nuclei Immunologic Stratum granulosum absent

Classification     

plaque psoriasis guttate psoriasis erythrodermic psoriasis pustular psoriasis psoriatic arthritis

Differential Diagnosis

Treatment  

no treatment needed; clears spontaneously in 6-12 weeks, reassurance topical corticosteroids when post-inflammatory pigmentation is a concern

atopic dermatitis, mycosis fungoides (cutaneous T-cell lymphoma), seborrheic dermatitis, tinea

PLAQUE PSORIASIS a common chronic and recurrent disease characterized by wellcircumscribed erythematous papules/plaques with silvery-

Clinical Pearl


decreased epidermal transit time from basal to horny layers shortened cell cycle of psoriatic and normal skin --> excess keratinization with scales

Epidemiology 

multifactorial inheritance

Clinical Pearl Woronoff’s Ring Woronoff’s ring: blanched halo that surrounds psoriatic lesions after topical or phototherapy treatments Signs and Symptoms 

Etiology suspected human herpes virus 7

Pathophysiology 

The 6 Ps of Lichen Planus Purple, Pruritic, Polygonal, Peripheral, Papules, Penis (i.e. mucosa)

white scales, mostly at sites of repeated trauma

 

 

worse in winter (lack of sun and humidity) Koebner phenomenon (isomorphic response): induction of new lesion by injury Auspitz’ sign: bleeds from minute points when scale is removed sites: scalp, extensor surfaces of elbows and knees, trunk, nails, pressure areas usually non-pruritic exacerbating factors: drugs (lithium, ethanol, chloroquine, betablockers), sunlight, stress, obesity

Treatment 

preventative measures: avoid sunburns, avoid drugs that exacerbate the condition (betablockers, lithium, corticosteroid rebound

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phenomenon, interferon, etc.) first-line treatment mainly involves topical treatments, usually prescribed if less than 510% of the body surfaces are involved. If the affected area is >10%, use topical medications as adjuncts to phototherapy or systemic drugs systemic treatments should be considered if: o psoriatic lesions cover >10% of the body surface area o unsuccessful topical therapies o disease is causing psychological distress

GUTTATE PSORIASIS ("DROP-LIKE") Definition and Clinical Features   

discrete, scattered salmon-pink scaling papules sites: generalized, sparing palms and soles often antecedent streptococcal pharyngitis

Treatment  

UVB phototherapy, sunlight, lubricants penicillin V or erythromycin if Group A beta-hemolytic Streptococcus on throat culture


   

generalized erythema with fine desquamative scale on surface associated symptoms: arthralgia, severe pruritus may present in patient with previous mild plaque psoriasis aggravating factors: lithium, beta-blockers, NSAIDs, antimalarials, phototoxic reaction, infection

 

   

asymmetric oligoarthropathy distal interphalangeal (DIP) joint involvement (predominant) rheumatoid pattern – symmetric polyarthropathy psoriatic arthritis mutilans (most severe form) predominant spondylitis or sacroiliitis

Rheumathoid Arthritis

Treatment 

hospitalization, bedrest, IV fluids, sun avoidance, monitor fluid and electrolytes treat underlying aggravating condition methotrexate, UV, oral retinoids, biologicals

chronic, symmetric, erosive synovitis of peripheral joints (i.e. wrists, MCP joints, and MTP joints) characterized by a number of extra-articular features

Clinical Pearl PUSTULAR PSORIASIS Definition and Clinical Features 

 

sudden onset of erythematous macules and papules which evolve rapidly into pustules, very painful can be generalized or localized to palms/soles patient usually has history of psoriasis; may occur with sudden withdrawal from steroid therapy

Treatment 

methotrexate, oral retinoids, biologicals


Definition and Clinical Features


Common Presentation Morning stiffness >30 min, improves with use Symmetric joint involvement Initially involves small joints of hands and feet Constitutional symptoms Clinical Pearl Criteria are 91-94% sensitive and 89% specific for RA. Table 7. Diagnostic Criteria: RA diagnosed if 4 or more of the following 7 criteria present (American Rheumatism Association, 1987) Criteria


Joint stiffness >1 1. Morning hour for >6 stiffness weeks 2. Arthritis of three or more joint areas

At least 3 active joints for >6 weeks; commonly involved joints

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are PIP, MCP, wrist, elbow, knee, ankle, MTP At least one 3. Arthritis active joint in of hand wrist, MCP or PIP joints for >6 weeks


molecular 

Common sites of joint involvement in mimicry RA

below) and radiographic damage limitation of function and decrease in global functional status

Bilateral 4. involvement of Symmetric PIP, MCP, or MTP arthritis for >6 weeks Subcutaneous nodules over bony 5. prominences, Rheumatoid extensor nodules surfaces or in juxta-articular regions 6. Serum RF

Etiology and Pathophysiology

Found in 60-80% of RA patients

Erosions or periarticular osteopenia, 7. likely to see Radiographi earliest changes c changes at ulnar styloid, 2nd and 3rd MCP and PIP joints


autoimmune disorder, unknown etiology hallmark of RA is hypertrophy of the synovial membrane o outgrowth of activated rheumatoid synovium (pannus) into and over the articular surface results in destruction of articular cartilage and subchondral bone two theories attempt to explain chronic remissions and exacerbations seen in RA o sequestered Ag

Signs and Symptoms  

 

variable course of exacerbations and remissions morning stiffness >1 hr, improves with use, aggravated by rest symmetric joint involvement signs of disease activity: synovitis (assessed by tender and swollen joint count), elevated serum markers of inflammation such as ESR or CRP, decreased grip strength, increased pain signs of mechanical joint damage: loss of motion, instability, deformity, crepitus constitutional symptoms: profound fatigue; rarely myalgia or weight loss extra-articular features (see Figure 7


 

RF positive in 80% of patients o non-specific, also seen in other rheumatic diseases (e.g. SLE, Sjogren’s), chronic inflammation (e.g. SBE, hepatitis, TB) and 5% of healthy population anti-CCP (cyclic citrullinated peptide): sensitivity (~80%) increased disease activity is associated with decrease Hb (anemia of chronic disease), increased platelets, elevated ESR, CRP, and RF

Classification of Global Functional Status in RA (American College of Rheumatology, 1991)  

Class I: able to perform usual ADLs (self-care, vocational, avocational) Class II: able to perform self-care and vocational activities, restriction of avocational activities

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rheumatic drugs (DMARDs)

Class III: able to perform self-care, restriction of vocational and avocational activities Class IV: limited in ability to perform selfcare, vocational, avocational activities

Clinical Pearl Poor prognostic features of RA include young age of onset, high RF titer, elevated ESR, activity of >20 joints, and presence of EAF.

Complications of Chronic Synovitis 

  

joint deformities (see Figure 8 below) o swan neck deformity, boutonnire deformity o ulnar deviation of MCP; radial deviation of wrist joint o hammer toe, mallet toe, claw toe o flexion contractures atlanto-axial and subaxial subluxation o C-spine instability o neurological impingement (long tract signs) o difficult intubation limited shoulder mobility, spontaneous tears of the rotator cuff leading to chronic spasm tenosynovitis => may cause rupture of tendons Carpal Tunnel Syndrome ruptured Bakers cyst (outpouching of synovium behind the knee); presentation similar to acute DVT decreased functional capacity and early mortality

Clinical Pearl Common Syndromes in RA 1. Sjogrens syndrome (sicca complex, dry eyes and mouth) 2. Caplan’s syndrome (multiple pulmonary nodules and pneumoconiosis) 3. Felty’s syndrome (arthritis, splenomegaly, neutropenia)

A) Education, occupational therapy, physiotherapy, vocational counselling 


goals of therapy o o o o o

control disease activity relieve pain and stiffness maintain function and lifestyle prevent or control joint damage key is early diagnosis and early intervention with disease modifying anti-


therapeutic exercise program (isometrics and active ROM exercise during flares, aquatic/aerobic/strength ening exercise between flares), assistive devices and patient education patients may need job modification, time off work or change in occupation

B) Medical 

NSAIDs, DMARDs, and corticosteroids are the mainstay of pharmacological therapy

1. Reduction of Inflammation and Pain

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NSAIDS individualize according to efficacy and tolerability 

bisphosphonat e, calcium, and vitamin D therapy if using corticosteroids >3 months at >7.5 mg/day

contraindicated or cautioned in some patients

analgesics 

side effects: osteoporosis, avascular necrosis (AVN), hypertension, catara cts, glaucoma, peptic ulcer disease (PUD), susceptibility to infection, hypokalem ia, hyperglycemia, hyperlipidemia, weight gain, acne

cautions/contraindica tions: active infection, osteoporosis, hypertension, gastric ulcer, diabetes, TB

add acetaminophen ± opioid prn for synergistic pain control

corticosteroids 

local o


intra-articular injections to control symptoms in a specific joint eye drops for eye involvement

systemic (prednisone) o


o o

low dose (5-10 mg/day) useful for (a) short term to improve symptoms if NSAIDs ineffective, (b) to bridge gap until DMARD takes effect or (c) for refractory disease moderate to high dose (2060+ mg/day) for cardiopulmon ary disease high dose (1 mg/kg/day) for vasculitis do baseline DEXA bone density scan and start

2. Disease Modifying Antirheumatic Drugs (DMARDs)  

 

combination DMARDs are the standard of care start DMARDs within 3 months of diagnosis to decrease disease progression, symptoms and signs DMARDs reduce or prevent joint damage, and are associated with better long-term disability index delayed onset of action (may take 8-12 weeks) many DMARDs have potential toxicities that require periodic monitoring if repetitive flares, progressive joint damage, or ongoing disease activity after 3 months of maximal


therapy > change or add other DMARDs mild and early stages: o hydroxychloroqui ne or sulfasalazine monotherapy preferred moderate to severe disease (especially if unfavourable prognostic factors): o methotrexate is the gold standard o single regimen with methotrexate or leflunomide o combination therapy: methotrexate + sulfasalazine + hydroxychloroqui ne; methotrexate + cyclosporine; methotrexate + leflunomide biologics: indicated if persistent disease activity o commonly used after failure of other DMARDs; however, evidence suggests benefit from use in early RA as well

Clinical Pearl Only DMARDs (not analgesics or NSAIDs) alter the course of RA! C) Surgical Therapy 

synovectomy: debridement and/or removal of inflamed synovium from individual joints (surgical or radioactive) joint replacement (hip, shoulder, knee)

Loren Warmington

  

joint fusion (wrist, thumb, ankle, Cspine) reconstruction (tendon repair) surgery indicated for structural joint damage

SLE Diagnostic Criteria of SLE: MD SOAP BRAIN Malar rash Blood Discoid rash Renal Serositis Arthritis Oral ulcers Immune ANA Neurologic Photosensitivity

Signs and Symptoms  

characterized by periods of exacerbation and remission systemic o fever, malaise, fatigue, lymphadenopathy , weight loss vascular o Raynaud’s phenomenon, thrombosis, vasculitis, livedo reticularis (mottled discolouration of skin due to narrowing of blood vessels, character istic lacy or netlike appearance) dermatologic o maculopapular rash, photosensitivity, panniculitis (inflammation of subcutaneous fat and muscle tissue), alopecia (hair loss), urticaria, purpura, oral, nasal, genital ulcers

ophthalmic o conjunctivitis, episcleritis, keratoconjunctivit is, cytoid bodies (cotton wool exudates on fundoscopy = infarction of nerve cell layer of retina) gastrointestinal o pancreatitis, lupus enteropathy, hepatitis, hepatomegaly pulmonary o interstitial lung disease, pulmonary hypertension, PE, alveolar hemorrhage, pleuritis musculoskeletal o arthralgias, arthritis, avascular necrosis, myositis neurologic o depression, personality disorder, cerebritis, transverse myelitis, seizures, headache, peripheral neuropathy

Treatment 

Investigations  

serologic hallmark is high titer ANA detected by immunofluorescence ANA has high sensitivity (98%) and therefore is a useful screening test, but poor specificity anti-dsDNA Ab (detected by Crithidia test, Farr radioimmunoassay) and anti-Sm Ab are specific for SLE (95-99%) a drop in anti-dsDNA titer and normalization of


serum complement (C3, C4) are useful to monitor response to treatment in patients who are clinically and serologically concordant lupus anticoagulant may cause increased risk of arterial and venous clotting and increased PTT

principles of therapy: o treat early and avoid long term steriod use if possible o if high doses of steroids necessary for long-term control add steroid sparing agents and taper when possible o treatment is tailored to organ system involved and severity of disease o all medications used to treat SLE require periodic monitoring for potential toxicites dermatologic o preventative: use sunscreen, avoid UV light and estrogens o topical steroids for rash, antimalarials musculoskeletal o bisphosphonates, calcium, vitamin D to combat osteoporosis o antimalarials (hydroxychloroqui ne if no serious internal organ involvement => improves long

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term control and prevents flares) o NSAIDs ± gastroprotective agent for arthritis (also beneficial for pleuritis and pericarditis organ threatening disease o systemic steroids to minimize end organ damage secondary to inflammation high-dose oral prednisone/IV methylprednisolo ne in severe disease o steroid sparing agents: azathioprine, methotrexate, mycophenolate o IV cyclophosphamid e for serious organ involvement (e.g. cerebritis or SLE nephritis)

Side Effects of Steroids Local:  Atrophy  Perioral dermatitis  Steroid acne  Rosacea  Contact dermatitis  Tachyphylaxis (tolerance) Systemic: Dermatological  Thin, fragile skin  Mild hirsutism  Bruising  Facial erythema  Increased sweating  Impaired wound healing,  Striae  Acne Growth suppression in children Hypertension Hyperlipidemia

Hyperglycemia Cushingoid Faces and buffalo hump Adrenal suppression and atrophy Weight gain, Na and water retention, K depletion Infections, especially viral, TB and fungal Osteoporosis, aseptic bone necrosis, ruptured Achilles Gastrointestinal  Despespsia, Peptic ulcer and perforation  Pancreatitis CNS  euphoria  Psychosis, increased intracranial pressure, increased tendency to epilepsy Cataracts, increased intra ocular pressure Amenorrhea, premature menopause Teratongenity (fetal cleft palate) Rebound disease on reducing dosage Myopathy or muscle atrophy

Diabetic Retinopathy 

Cataracts   

any opacity of the lens most common cause of reversible blindness worldwide types: nuclear sclerosis, cortical, posterior subcapsular (see Figure 16 below)

 

Etiology acquired o age-related (over 90% of all cataracts)


cataract associated with systemic disease (may have juvenile onset)  diabetes mellitus  metabolic disorders (e.g. Wilson’s disease, galactose mia, homocysti nuria)  hypocalce mia o traumatic (may be rosette shaped) o intraocular inflammation (e.g. uveitis) o toxic (steroids, phenothiazines) o radiation congenital o present with altered red reflex or leukocoria o treat promptly to prevent amblyopia o

most common cause of blindness in young people in North America blurring of distance vision with rise of blood sugar consider DM if unexplained retinopathy, cataract, EOM palsy, optic neuropathy, sudden change in refractive error loss of vision due to o progressive microangiopathy, leading to macular edema o progressive diabetic retinopathy -->

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neovascularizatio n --> traction --> retinal detachment and vitreous hemorrhage rubeosis iridis (neovascularizatio n of the iris) leading to neovascular glaucoma (poor prognosis) macular ischemia

Clinical Pearl Macular edema is the most common cause of visual loss in patients with background DR. Background: 

altered vascular permeability (loss of pericytes, breakdown of blood-retinal barrier, thickening of basement membrane) retinal vessel closure

Classification 

non-proliferative: increased vascular permeability and retinal ischemia o dot and blot hemorrhages o microaneurysms o hard exudates (lipid deposits) o macular edema advanced nonproliferative (or preproliferative): o non-proliferative findings plus o venous beading (in 2 of 4 retinal quadrants) o intraretinal microvascular anomalies (IRMA) in 1 of 4 retinal quadrants

IRMA: dilated, leaky vessels within the retina o cotton wool spots (nerve fibre layer infarcts) proliferative o 5% of patients with diabetes will reach this stage o neovascularizatio n: iris, disc, retina to vitreous o neovascularizatio n of iris (rubeosis iridis) can lead to neovascular glaucoma o vitreous hemorrhage from bleeding fragile new vessels, fibrous tissue can contract causing tractional retinal detachment o increased risk of severe visual loss 

Clinical Pearl Presence of DR in: Type 1 DM 25% after 5 years 60% after 10 years >80% after 15 years

Treatment 

  

Type 2 DM 20% at time of diagnosis 60% after 20 years Screening Guidelines for Diabetic Retinopathy 

Type 1 DM o screen for retinopathy beginning annually 5 years after disease onset o screening not indicated before the onset of puberty


Type 2 DM o initial examination shortly after diagnosis, then repeat annually pregnancy o ocular exam in 1st trimester, close follow-up throughout as pregnancy can exacerbate DR o gestational diabetics not at risk for retinopathy

Diabetic Control and Complications Trial (DCCT) o tight control of blood sugar decreases frequency and severity of microvascular complications blood pressure control focal laser for clinically significant macular edema panretinal laser photocoagulation, for proliferative diabetic retinopathy, reduces neovascularization, hence reducing the angiogenic stimulus from ischemic retina by decreasing retinal metabolic demand --> reduces risk of blindness vitrectomy for vitreous hemorrhage and retinal detachment in proliferative diabetic retinopathy which is complicated by nonclearing vitreous hemorrhage or retinal detachment the diabetic retinopathy vitrectomy study indicated that vitrectomy

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before vitreous hemorrhage does not improve the visual prognosis Lens Changes   

earlier onset of senile nuclear sclerosis and cortical cataract may get hyperglycemic cataract, due to sorbitol accumulation (rare) sudden changes in refraction of lens: changes in blood glucose levels (poor control) may cause refractive changes by 3-4 diopters

Hypertensive Retinopathy 

retinopathy is the most common ocular manifestation of hypertension key features of chronic HTN retinopathy: AV nicking, blot retinal hemorrhages, microaneurysms, cotton wool spots key features of acute HTN retinopathy: retinal arteriolar spasm, superficial retinal hemorrhage, cotton-wool spots, optic disc edema


Glaucoma 

 

Mild to moderate Grou narrowing or sclerosis p1 of the arterioles

Grou Retinal arteriolar

Grou Same as group 3, plus p 4 papilledema

Table 6. Keith-WagenerBarker Classification

Grou Moderate to marked p 2 narrowing of the arterioles Local and/or generalized narrowing of arterioles Exaggeration of the light reflex Arteriovenous crossing changes (AV nipping)

narrowing and focal constriction Retinal edema Cotton-wool patches Hemorrhage

 

aqueous is produced by the ciliary body and flows from the posterior chamber to the anterior chamber through the pupil, and drains into the episcleral veins via the trabecular meshwork and the canal of Schlemm an isolated increase in IOP is termed ocular hypertension (or glaucoma suspect) and these patients should be followed for increased risk of developing glaucoma (~10% if IOP = 20-30 mmHg; 40% if IOP = 30-40 mmHg; and most if IOP >40 mm Hg) average IOP is 15 ± 3 mm Hg (diurnal variation, higher in a.m.) pressures >21 mmHg more likely to be associated with glaucoma; however, up to 50% of patients with glaucoma do not have IOP >21mmHg normal C:D (cup:disc) ratio 0.6, C:D ratio difference between eyes >0.2 or cup approaches disc margin loss of peripheral vision most commonly precedes central loss sequence of events: gradual pressure rise, followed by increased C:D ratio, followed by visual field loss


screening tests should include: o medical and family history o visual acuity testing o slit lamp exam to assess anterior chamber depth o ophthalmoscopy to assess the disc features o tonometry by applanation or indentation to measure the IOP o visual field testing

Features of Papilledema  Engorged retinal veins  Loss of cupping  Pink disk with blurred margins  Cribosa not visible  Flamed shaped hemorrhages Causes of Papilledema   

central retinal vein occlusion systemic illness HTN, vasculitis, hypercapnia

Loren Warmington

 

toxic/metabolic/nutrition al deficiency infiltration o neoplastic: leukemia, lymphoma, glioma o non-neoplastic: sarcoidosis pseudotumour cerebri o idiopathic signs and symptoms of increased ICP, with a normal CT o usually in obese young women compressive o meningioma, hemangioma, thyroid ophthalmopathy

Optic Atrophy Damage to the optic nerve from many different kinds of pathologies. Not a disease, but rather a sign of an underlying condition Causes:        

glaucoma, anterior ischemic optic neuropathy, retinal lesions eg. chorioretinitis, intraocular bleed tumour, aneurism or pagets disease pressing on the optic nerve, optic neuritis (retrobulbar neuritis) Leber’s hereditary optic neuropathy, Congenital Division of optic nerve – surgeryor trauma

Signs and symptoms:  low visual acuity,  peripheral vision impairment,  difficulty with colour vision,

pallor of the optic disc on fundoscopy

Management: optic nerve atrophy is an irreversible condition, management of the underlying condition is crucial to prevent exacerbation

Transient Loss of Vision (lasting seconds to hours)   

transient ischemic attack (TIA) migraine with aura papilledema

Acute Loss of Vision (occurring in seconds to days) Clinical Pearl Top 3 in DDx of Acute Loss of Vision 1. trauma/foreign body 2. retinal artery/vein occlusion 3. retinal detachment

Cortical/Other:   

occipital infarction/hemorrhage cortical blindness functional (non-organic, diagnosis of exclusion)

Chronic Loss of Vision (occurring over weeks to months) Clinical Pearl Top 3 in DDx of Chronic Loss of Vision Reversibl e 1.Catarac t 2.Refracti ve error 3. corneal dystrophy

Cornea/Anterior Segment: 

Cornea/Anterior Segment:    

corneal edema hyphema acute angle-closure glaucoma trauma/foreign body

Vitreous/Retina/Optic Nerve:       

vitreous hemorrhage retinal detachment retinal artery/vein occlusion acute macular lesion optic neuritis temporal arteritis anterior ischemic optic neuropathy (AION)


Irreversible 1. age-related macular degeneration 2. glaucoma 3. diabetic retinopathy

  

corneal dystrophy, scarring, edema refractive error cataract glaucoma

Vitreous/Fundus/Optic Nerve:    

 

age-related macular degeneration (ARMD) diabetic retinopathy retinal vascular insufficiency compressive optic neuropathy (intracranial mass, orbital mass) intraocular neoplasm retinitis pigmentosa (RP)


Loren Warmington

  

pituitary adenoma medication-induced (sildenafil, amiodarone) nutritional deficiency

 

Causes of Red Eye 

lids/orbit/lacrimal system o hordeolum/chalazi on o blepharitis o foreign body/laceration o dacryocystitis/dac ryoadenitis Conjunctiva/sclera o subconjunctival hemorrhage o conjunctivitis o dry eyes o pterygium/pingue cula o episcleritis/scleriti s o preseptal/orbital cellulitis cornea o foreign body o keratitis o abrasion, laceration o ulcer anterior chamber o uveitis (iritis, iridocyclitis) o acute angleclosure glaucoma o hyphema o hypopyon endophthalmitis

Polcystic Kidey Disease 

PKD1 (1:400), PKD2 (1:1,000), accounts for about 10% of cases of renal failure autosomal dominant; at least 3 genes: PKD1 (chr 16p), PKD2 (chr 4q), PKD3 (location not yet determined) polycystin protein from PKD1 responsible for cell-

cell and cell-matrix interaction defect can lead to abnormal cell growth and cyst formation extrarenal manifestations: most common; multiple asymptomatic hepatic cysts (33%) cerebral aneurysm (10%), diverticulosis and mitral valve prolapse (25%) polycystic liver disease rarely causes liver failure o less common: cysts in pancreas, spleen, thyroid, ovary, seminal vesicles, and aorta

flank and chronic back pain Clinical Course    

Signs and Symptoms 

   

often asymptomatic; discovered incidentally on imaging or by screening those with FHx acute abdominal flank pain/dull lumbar back pain hematuria (microscopic frequently initial sign, gross) nocturia (urinary concentrating defect) rarely extra-renal presentation (e.g. ruptured berry aneurysm, diverticulitis) HTN (increased renin due to focal compression of intrarenal arteries by cysts) (60-75%) ± palpable kidneys

Treatment 

Common Complications 

urinary tract and cyst infections, HTN, CRF, nephrolithiasis (5-15%),


polycystic changes are always bilateral and can present at any age clinical manifestations rare before age 20-25 kidneys are normal at birth but may enlarge to 10 times normal volume variable progression to renal functional impairment (ESRD in up to 50% by age 60) investigations radiographic diagnosis – best accomplished by renal U/S (enlarged kidneys, multiple cysts throughout renal parenchyma, increased cortical thickness, splaying of renal calyces) CT abdo with contrast (for equivocal cases, occasionally reveals more cystic involvement) gene linkage analysis for PKD1 for asymptomatic carriers o Cr, BUN, urine R&M (to assess for hematuria)

goal: to preserve renal function by prevention and treatment of complications educate patient and family about disease, its manifestations and inheritance pattern genetic counselling: transmission rate 50% from affected parent prevention and early treatment of urinary tract and cyst infections (avoid instrumentation of GU tract) TMP/SMX, ciprofloxacin: able to penetrate cyst

Loren Warmington

  

 

walls, achieve therapeutic levels adequate hydration to prevent stone formation avoid contact sports due to greater risk of injury to enlarged kidneys screen for cerebral aneurysms if strong family history of aneurysmal hemorrhages monitor blood pressure and treat hypertension with ACEI dialysis or transplant for ESRD (disease does not recur in transplanted kidney) may require nephrectomy to create room for renal transplant

Chronic Renal Disease abnormal markers (Cr, urea)   

GFR 3 months or kidney pathology seen on biopsy or decreased renal size on U/S

Stages of Chronic Kidney Disease (K/DOQI, 2002) GFR Definiti (mL/min/1.73 on m2) Normal Stag or >90 e 1 increase d GFR Mild Stag decrease 60-89 e2 in GFR Moderat Stag e 30-59 e 3 decrease in GFR Severe Stag decrease 15-29 e4 in GFR End Stag stage in ATN increase - WBC in d [Cr] AIN - urine - RBC in [Na] GN 500 mOsm/k g fraction al

Clues to PostRenal Etiology - known solitary kidney - older man - recent retroperiton eal surgery - anuria - palpable bladder ultrasound indicates hydronephr osis

excretio n of Na < 1%

Indications for Dialysis in AKI

Clinical Pearl Differentiating Pre-renal from ATN PreATN renal RBC, Urinalysi norma pigmented s l granular casts Urine [Na]

40 [Cr]/[Na]

40 mEq/L 35 mM) Pericarditis Encephalopathy Edema (pulmonary)


Investigations 

    

blood: CBC, electrolytes, Cr, BUN (think prerenal if increase in BUN is relatively greater than increase in Cr), Ca, PO4 urine volume, C&S, R&M: sediment, casts, crystals urinary indices foley catheterization (rule out bladder outlet obstruction) fluid challenge (i.e. fluid bolus to rule out most prerenal causes) imaging: abdo U/S (assess kidney size, hydronephrosis, postrenal obstruction) indications for renal biopsy: o diagnosis is not certain o prerenal azotemia or ATN is unlikely o oliguria persists >4 weeks

Red Flag


pre-renal o correct prerenal factors: optimize volume status and cardiac performan ce renal o exclude reversible renal causes: d/c nephrotoxic drugs, treat infection, optimize electrolytes and hold ACEI/ARB post-renal o consider obstruction: structural (stones, strictures) vs. functional (neuropathy) o treat with foley catheter, indwelling bladder catheter, nephrostomy, stenting

2) treat complications 

fluid overload o NaCl restriction o high dose loop diuretics o hyperkalemia (refer to Treatment of Hyperkalemia)

Loren Warmington

adjust dosages of medications cleared by kidney 3) definitive therapy depends on etiology Note: Renal transplant is not a therapy for AKI (unlike other organs eg: liver) o

 

Prognosis 

high morbidity with multi-organ failure, most commonly in prerenal azotemia (ischemic insult)

Treatment of Hyperkalemia 

serum K >5.0 mEq/L

Approach to Hyperkalemia 

    

1. emergency measures: obtain ECG, if life threatening begin treatment immediately 2. rule out factitious hyperkalemia; repeat blood test 3. hold exogenous K, and any K retaining medications 4. assess potential causes of transcellular shift 5. estimate GFR (calculate CrCl/use Cockcroft-Gault) 6. if normal GFR, calculate TTKG = (Uk/Pk)/ (Uosm/Posm) o TTKG 7 = normal aldosterone function

Incr Cellula eas Factiti r ed ous Releas Inta e ke Prolon Diet ged use of KCl tourniq tabs uet IV Sampl KCl e taken from vein where IV KCl is runnin g Sampl e hemol ysis Leukoc ytosis (extre me) Throm bocyto sis (extre me)

Decrea sed Excreti on

Intrava Decreas scular ed GFR hemoly • sis renal Rhabdo failure myolysi • low s effective Insulin circulati deficien ng cy volume Hypero • smolar NSAIDs states in renal (e.g. insuffici hypergl ency ycemia) Normal GFR but Metabol hypoald ic osteroni acidosis sm (see (except Table 7 for below) ketoand lactic acidosis ) Tumour lysis syndro me Drugs • betablocker s • Digitalis overdos e (blocks Na-K ATPase) • Succiny lcholine

Figure 12. EKG Changes in Hyperkalemia

Signs and Symptoms 

 

usually asymptomatic but may develop nausea, palpitations, muscle weakness, muscle stiffness, paresthesias, areflexia, ascending paralysis, and hypoventilation impaired renal ammoniagenesis and metabolic acidosis ECG changes and cardiotoxicity (do not correlate well with K concentration) o peaked and narrow T waves o decreased amplitude and eventual loss of P waves o prolonged PR interval o widening of QRS and eventual merging with T wave (sine-wave pattern) o AV block o ventricular fibrillation, asystole

Clinical Pearl In patients with diabetes, increased K and hyperglycemia, often just giving insulin to restore euglycemia is sufficient to correct the hyperkalemia. Mnemonic Treatment of Hyperkalemia SEE BIG K DROP

Causes of Hyperkalemia


Loren Warmington

SEE - Calcium gluconate BIG - B-agonist, Bicarb, Insulin, Glucose K - KayexalateTM DROP - Diuretics, Dialysis

Treatment 

acute therapy is warranted if ECG changes present, K high, symptoms present tailor therapy to severity of increase in K and ECG changes o K 7.0 and/or ECG changes: first priority is to protect the heart: add Ca gluconate to above

Ca gluconate 1-2 amps (10 mL of 10% solution) IV antagonizes cardiac toxicity of hyperkalemia, protects cardiac conduction system, no effect on serum K onset within minutes, lasts 30-60 minutes

2. Shift K into Cells

A. via urine o furosemide (>40 mg IV), may need IV NS to avoid hypovolemia o fludrocortisone (synthetic mineralocorticoid) if suspect aldosterone deficiency B. via gut o cation-exchange resins: calcium resonium or Kayexalateâ„¢ (less preferred because it binds


Na in exchange for K) plus sorbitol PO to avoid constipation o Kayexalateâ„¢ enemas with tap water (not sorbitol) C. dialysis (renal failure, life threatening hyperkalemia unresponsive to therapy)

Presentation of Glomerular Disease Each glomerulonephropathy presents as one of 4 major glomerular syndromes    

acute nephritic nephrotic rapidly progressive glomerulonephritis asymptomatic urinary abnormalities

each glomerulonephropathy can be caused by a primary disease OR can occur secondary to a systemic disease 

3. Enhance K Removal from Body

1. Protect the Heart 

regular insulin (Insulin R) 10-20 units IV, with 1-2 amp D50W o onset of action 15-30 min, lasts 1-2 h o monitor blood glucose q1h o can repeat every 4-6 hours, or give infusion of 1 unit/hour NaHCO3 1-3 amps (given as 3 amps of 7.5% or 8.4% NaHCO3 in 1L D5W) o onset of action 15-30 min, transient effect, drives K into cells in exchange for H beta2-agonist (Ventolinâ„¢) in nebulized form (dose = 2 cc or 10 mg inhaled) or 0.5 mg IV o onset of action 30-90 min, stimulates Na-K ATPase o caution if patient has heart disease as tachycardia may result from this high dose of beta2-agonist

some glomerulonephropathies can present as more than one syndrome at different times

1) ACUTE NEPHRITIC SYNDROME Clinical/Lab Features     

proteinuria (3.5 g/d) 2) hypoalbuminemia 3) edema 4) hyperlipidemia, lipiduria 5) oval fat bodies (microscopy) 6) hypercoagulable state (protein C and protein S lost in urine)

minimal change disease (or minimal lesion disease or nil disease) – i.e. glomeruli appear normal on light microscopy o membranous glomerulopathy o focal segmental glomerulosclerosi s (FSGS) o membranoprolifer ative glomerulonephriti s each can be idiopathic or secondary to a systemic disease or drug o

Investigaton of Glomerular disease Blood work  

first presentation: electrolytes, Cr, urea, albumin, fasting lipids determining etiology: CBC, ESR, serum immune electrophoresis, C3, C4, ANA, p-ANCA, cANCA, cryoglobulins, HBV, HCV serology, ASOT (anti-streptolysin - O titres), VDRL, HIV

 urinalysis: RBCs, WBCs, casts, protein  24 hr urine for protein and CrCl  radiology

Clinical/Lab Features       

heavy proteinuria (>3.5 g/1.73m2/d) hypoalbuminemia edema hyperlipidemia, lipiduria, fatty casts and oval fat bodies on microscopy hypercoagulable state (i.e. Protein C and Protein S urinary losses) glomerular pathology on renal biopsy:

CXR (infiltrates, CHF, pleural effusion) renal ultrasound

 renal biopsy (percutaneous or open)  urine immunoelectrophoresis 

for Bence Jones protein if proteinuria present


Systemic Lupus Erythematosus  

lupus nephritis can present as any of the glomerular syndromes nephrotic syndrome with an active sediment is most common presentation glomerulonephritis caused by immune complex deposition in capillary loops and mesangium with resulting renal injury serum complement levels are usually low during periods of active renal disease children and males with SLE are more likely to develop nephritis

HIV-Associated Renal Disease 

1) direct nephrotoxic effect of HIV infection, antiretroviral drugs (e.g. tenofovir, indinavir) and other drugs used to treat HIV-associated infections 2) HIV-associated nephropathy o histology: focal and segmental glomerular collapse with mesangial sclerosis, “collapsing FSGS” o tubular cystic dilation and tubulo-reticular inclusions o clinical features: predominant in black men, heavy proteinuria, progressive renal insufficiency o prognosis: kidney failure within one year without treatment

Loren Warmington


therapy: shortterm, high dose steroids, ACEI, HAART 

Amyloidosis 

 

nodular deposits of amyloid in mesangium, usually related to AL amyloid presents as nephritic range proteinuria with progressive renal insufficiency can be primary or secondary secondary causes: multiple myeloma, TB, rheumatoid arthritis, malignancy

Sickle Cell Disease 

sickling disorders due to a mutant beta globin chain, most commonly caused by a Glu --> Val substitution at position 6 resulting in HbS rather than HbA Sickle cell anemia occurs when an individual has two HbS genes (homozygous) or one HbS gene + another mutant beta globin gene (compound heterozygote)

at low pO2, deoxy HbS polymerizes, leading to rigid crystal-like rods that distort membranes --> ‘sickles’ the pO2 level at which sickling occurs is related to the percentage of HbS present o in heterozygotes (HbAS), sickling occurs at a pO2 of 40 mmHg



Clinical Features o

HbAS (heterozygous): patient will appear normal except at times of extreme hypoxia and infection (sickle cell trait)


HbSC (most common compound heterozygote)   

milder anemia similar clinical features to HbSS although milder spleen not always atrophic in adult


HbSS (homozygous)   

Pathophysiology 

in homozygotes (HbSS), sickling occurs at a pO2 of 80 mmHg sickling is aggravated by increased H+, increased CO2, increased 2,3DPG, increased temperature and osmolality sickle cells are fragile and hemolyze; they also block small vessels o

 

chronic hemolytic anemia jaundice in the first year of life may have retarded growth and development +/- skeletal changes spleen enlarged in child and atrophic in adult types of crises: o I. Aplastic crises o toxins and infections (especially parvovirus B19) transiently suppress bone marrow activity o II. Splenic sequestration crises


usually in children, with significant pooling of blood in spleen, resulting in acute decreased Hb and shock uncommon in adults because of functional asplenia from repeated infarction (adults with HbSC may not have functional asplenia) III. Vaso-occlusive crises (infarction) may affect many different organs causing pain (especially in back, chest, abdomen and extremities), fever, and leukocytosis (e.g. acute chest syndrome) precipitated by infections, dehydration, rapid change in temperature, pregnancy, menses and alcohol

o Table 5. Investigations for Sickle Cell Disease HbAS



increased reticuloc yte, normal decrease d Hb, decrease d Hct

normal; possibl Peripheral sickled y a few blood cells target cells Hb


No HbA,

Loren Warmington

fraction Only HbS of 0.65 and HbF. (65%); electrophor Proportio HbS esis ns fraction change of 0.35 with age. (35%)


+ve sickle cell prep (screen ing test) 

Hb electrophoresis distinguishes HbAS, HbSS and other variants

Treatment   

genetic counseling folic acid to prevent folate deficiency hydroxyurea to enhance production of HbF o stops repression of the gene for HbF or initiates differentiation of stem cells in which this gene is active o presence of HbF in the SS cells decreased polymerization and precipitation of HbS o note: hydroxyurea is cytotoxic and may cause bone marrow suppression treatment of vasoocclusive crisis o oxygen (only if hypoxic) o hydration (reduces viscosity) o antimicrobials o correct acidosis o analgesics/narcoti cs (give enough)

magnesium (inhibits potassium and water efflux from RBCs thereby preventing dehydration) o indication for exchange transfusion: acute chest syndrome, stroke, bone marrow necrosis, priapism, and CNS crisis prevention of crises is key o establish diagnosis o avoid conditions that favour sickling (hypoxia, acidosis, dehydration, fever) o vaccination in childhood (e.g. pneumococcus (heptavalent and 23-valent), meningococcus, Hib) o prophylactic penicillin from 3 months until 5 years of age o good hygiene, nutrition, and social support screening for potential complications o regular bloodwork (CBC, retic, iron indices, BUN, LFTs, creatinine) o urinalysis annually o transcranial doppler annually until 16 years old o retinal examinations annually from 8 years old o echocardiography every two years from 10 years old

(to screen for pulmonary hypertension)



Clinical Pearl Functional asplenism increased susceptibility to infection by encapsulated organisms S. pneumoniae N. meningitidis H. influenzae Salmonella (osteomyelitis) Figure 8. Pathophysiology of Sickling

Organs Affected by VasoOcclusive Crisis Organ



seizures, stroke


hemorrhage, blindness


infarcts, RUQ syndrome


chest syndrome, long-term pulmonary hypertension

gall stones bladder heart

hyperdynamic flow murmurs


enlarged (child); atrophic (adult)

Loren Warmington


hematuria; loss of renal concentrating ability

intestine acute abdomen s placenta stillbirths penis




femoral avascular necrosis head bone

infarction, infection


leg ulcers

Clinical Pearl Acute Chest Syndrome Affects 30% of patients with sickle cell disease and may be life threatening. Presentation includes dyspnea, chest pain, fever, tachypnea, leukocytosis, and pulmonary infiltrate on CXR. Caused by vaso-occlusion, infection or pulmonary fat embolus from infarcted marrow. Cirrhosis 

diffuse, irreversible fibrosis plus hepatocellular nodular regeneration decompensated cirrhosis: means development of ascites +/- increased bilirubin +/- encephalopathy +/increased INR

 


    

alcohol (85%) chronic viral hepatitis (B, B+D, C but not A nor E) autoimmune hemochromatosis alpha-1-antitrypsin deficiency drugs and toxins o methotrexate biliary cirrhosis

Complications hematologic changes in cirrhosis 

Varices Anemia Renal failure Infection Coagulopathy Encephalopathy Sepsis

 

definitive diagnosis is histologic (liver biopsy) other tests may be suggestive: o blood work: liver enzymes, bilirubin, PT/PTT, increased gamma globulin, decreased albumin o imaging: U/S is the primary imaging modality, then CT

Management    

treat underlying disorder alcohol cessation follow patient for complications (see below) prognostic factors include


pancytopenia from hypersplenism decreased clotting factors o fibrin, thrombin, I, II, V, VII, IX, X

renal failure in cirrhosis 


nutrition (EtOH consumption) o ascites o varices o encephalopathy o labs: albumin, INR, bilirubin, creatinine liver transplantation for end-stage disease if no alcohold for >6 months o

Cirrhosis Complications: VARICES

Etiology  

o primary o secondary chronic hepatic congestion o cardiac cirrhosis (chronic right heart failure, constrictive pericarditis) o hepatic vein thrombosis (BuddChiari) idiopathic rare - Wilson’s disease, Gauchers

classifications o pre-renal (usually due to overdiuresis) o acute tubular necrosis (ATN) o hepatorenal syndrome o hepatorenal syndrome can occur at any time in severe liver disease, especially after:  overaggres sive diuresis or large volume paracentes is  GI bleeding  sepsis differentiate hepatorenal syndrome from prerenal failure

Loren Warmington

o o o



prerenal azotemia = hepatorenal lab findings clinical (very difficult) intravenous fluid challenge (giving volume expanders improves prerenal failure but not hepatorenal syndrome) pulmonary capillary wedge pressure measurements (PCWP) (preferable)

differentiate hepatorenal syndrome from ATN treatment for hepatorenal syndrome is generally unsuccessful  vasopressi n, octreotide, midodrine (increased renal blood flow by increased systemic vascular resistance)  definitive treatment is liver transplant hepatopulmonary syndrome (HPS) o present in patients with the triad of  1) liver disease  2) increased alveolararterial gradient while o

 

breathing room air, and  3) evidence for intrapulmo nary vascular abnormalit ies o majority of cases due to cirrhosis, though can be due to other chronic liver diseases, such as noncirrhotic portal hypertension o thought to arise from ventilationperfusion mismatch, intrapulmonary shunting and limitation of oxygen diffusion failure of damaged liver to clear circulating pulmonary vasodilators, versus the production of a vasodilating substance by the liver) clinical features: hyperdynamic circulation with cardiac output >7 L at rest and decreased pulmonary + systemic resistance dyspnea, platypnea (increase in dyspnea in upright position, improved by recumbency) and orthodeoxia (desaturation in the upright position, improved by recumbency) diagnosis via contrastenhanced echocardiography; demo nstrates intrapulmonary shunting


only proven treatment is liver transplantation

Hepatic Encephalopathy acute neuropsychiatric syndrome secondary to liver disease Pathophysiology porto-systemic shunt around hepatocytes and decreased hepatocelular function increases toxins (believed to be ammonia from gut, mercaptans, fatty acids, amino acids) to brain Precipitating Factors 

   

nitrogen load (GI bleed, protein load from food intake, renal failure, constipation) drugs (narcotics + CNS depressants) electrolyte disturbance (hypokalemia, alkalosis, hypoxia, hypovolemia) infection (spontaneous bacterial peritonitis) deterioration in hepatic function or superimposed liver disease

Stages 

 

I: apathy, restlessness, reversal of sleep-wake cycle, slowed intellect, impaired computational abilities, impaired handwriting II: asterixis, lethargy, drowsiness, disorientation III: stupor (rousable), hyperactive reflexes, extensor plantar responses IV: coma (response to painful stimuli only)


Loren Warmington

 

distinguish from nonliver-related neuropsychiatric disease in a patient with liver problems (e.g. alcohol withdrawal or intoxication, sedatives, subdural hematoma, metabolic encephalopathy) also distinguish from the causes of metabolic encephalopathy (e.g. renal failure, respiratory failure, severe hyponatremia, hypoglycemia); all easy to exclude/confirm diagnosis chiefly clinical, supported by laboratory findings, exclusion of other neuropsychiatric diseases only pathognomonic finding is fetor hepaticus characteristic EEG findings: diffuse (nonfocal), slow, high amplitude waves 

Treatment  

treat underlying liver disease and precipitating factors decrease generation of nitrogenous compounds o decreased dietary protein to 50 g/day; vegetable protein is better tolerated than animal protein o lactulose  prevents diffusion of NH3 (ammonia) from the colon into blood by lowerin g pH and forming non-

 

diffusible NH4+ (ammoniu m)  serves as a substrate for incorporati on of ammonia by bacteria, promotes growth in bowel lumen of bacteria which produce minimal ammonia  also acts as a laxative to eliminate nitrogenproducing bacteria from colon if inadequate response with lactulose, may try antibiotics broad-spectrum antibiotics (metronidazole, neomycin, rifaximin) eliminate ammonia producing bacteria from bowel lumen neomycin is less effective than lactulose plus more side effects (ototoxicity, nephrotoxicity) combination of the two may be more effective for resistant cases only avoid causing severe diarrhea with lactulose to decrease fluid/electrolyte problems best acute treatment in comatose patient is tap water enemas until clear


Precipitating Factors for Hepatic Encephalopathy Hemorrhage in GI tract/Hyperkalemia Excess dietary protein Paracentesis Acidosis/Anemia Trauma Infection Colon surgery Sedatives Portal Hypertension Pathophysiology  

pressure = flow x resistance unlikely that increased flow alone can cause portal hypertension (although described in AV-fistula or massive splenomegaly) 3 sites of increased resistance o pre-sinusoidal (e.g. portal vein thrombosis, schistosomiasis, sarcoidosis) o sinusoidal (e.g. cirrhosis, alcoholic hepatitis) o post-sinusoidal (e.g. right-sided heart failure, hepatic vein thrombosis, venoocclusive disease, constrictive pericarditis) signs of portal hypertension:

Clinical Pearl Portal Hypertension Cause = increase flow AND increase resistance Signs Esophageal varices Melena Splenomegaly Ascites Hemorrhoids Management


Loren Warmington

beta-blockers Nitrates Shunts [e.g. Transjugular intrahepatic portosystemic shunt (TIPS)] Management 

beta-blockers (propanolol, nadolol) and nitrates decreases risk of bleeding from varices shunts o goal: decrease portal venous pressure o transjugular intrahepatic portosystemic shunt (TIPS): interventional radiologist creates a shunt between portal and hepatic vein via a catheter placed in the liver o can be used to stop acute bleeding or prevent rebleeding o shunt usually remains open for no longer than up to one year o other (rare): portocaval, distal spleno-renal (Warren shunt)

Etiology Table 18. Serum-Ascites Albumin Gradient as an Indicator of the Causes of Ascites * in nephrotic syndrome: decreased serum [Alb] to begin with therefore gradient not helpful serum [Alb] serum [Alb] - ascitic ascitic [Alb] [Alb] 11 g/L g/L Cirrhosis/sever Peritoneal e hepatitis carcinomatos Chronic hepatic is congestion TB (right heart Pancreatic failure, Budddisease Chiari) Serositis Massive liver Nephrotic metastases syndrome* Myxedema

Child-Pugh Classification *Note: Childs classification is rarely used for shunting, but is still useful to quantitate the severity of cirrhosis Score: 5-6 (Child’s A), 7-9 (Child’s B), 10-15 (Childs C) Ascites 

accumulation of excess free fluid in the peritoneal cavity

Pathogenesis of Ascites in Cirrhosis 

normal physiology o intravascular hydrostatic pressure (HP) and oncotic pressure (OP) are balanced (Starling forces) --> preventing accumulation of extravascular fluid into peritoneal space in cirrhosis, HP and OP balance is disrupted, precipitating ascites by one or more of the following mechanisms:

Clinical Pearl


fibrotic constriction of sinusoids resulting in portal HTN and increased HP --> increased HP drives fluid lymphatic drainage into the abdomen across hepatic capsule and mesentery o renal hypoperfusion --> Na and H2O retention o PGE opposes sodium retention (NSAIDs may precipitate renal failure) o less important fact is hypoalbuminemia --> decreased OP underfill theory o portal hypertension and hypoalbuminemia lead to transudation of Na and water into peritoneum causing decreased intravascular volume and secondary renal sodium and water retention via reninangiotensinaldosterone system overflow theory o liver disease primarily causes renal retention of Na and water which then "overflows" into peritoneal cavity combined theory (incorporating both above theories) is most popular o

Secondary bacterial peritonitis (as opposed to primary bacterial peritonitis) usually results from a perforated viscus or surgical manipulation.

Loren Warmington




liver disease causes vasodilation via nitric oxide, increasing vascular capacitance decreased effective intravascular volume (i.e. volume to capacitance ratio low, but absolute volume is high) secondary urinary Na and water retention

Complication: Bacterial Peritonitis

clinically detectable when >500 mL

Investigations 

diagnostic paracentesis should be done on most patients: o cells and differential o chemistry (albumin, protein, amylase, TG) o C&S, gram stain o cytology (usually positive in peritoneal carcinomatosis) 

Treatment 

therapeutic paracentesis safe, especially if albumin infusion given concomitantly medical o Na restriction o diuretics (spironolactone, furosemide) o aim for 0.5 kg loss per day to prevent ARF (this

needed for diagnosis) treatment o IV antibiotics (cefotaxime is the treatment of choice until C&S is available) for 510 days; prophylaxis with daily norfloxacin

Tests of Liver Function Prothrombin Time (PT)

Diagnosis 

is maximum rate of ascitic fluid) o 1 kg loss per day if peripheral edema surgical o TIPS, liver transplantation (reserved for medically refractory cases)

primary/spontaneous bacterial peritonitis (SBP) o complicates ascites, does not cause it (occurs in 10% of cirrhotic ascites) o 1/3 of patients are asymptomatic, thus do not hesitate to do a diagnostic parace ntesis o fever, chills, abdominal pain, ileus, hypotension, worsening encephalopathy o gram negatives compose 70% of pathogens: E. coli (most common pathogen), Strept ococcus, Klebsiella diagnosis: o absolute neutrophil count in peritoneal fluid >0.25x109 cells/L (250 cells/mm3) or WBC count >0.5x109 cells/L (500 cells/mm3) o gram stain is positive in only 10-50% of patients o culture is positive in only 80% of patients (not


 

daily marker of hepatic protein synthesis must exclude co-existing vitamin K deficiency

Serum Bilirubin  

product of heme metabolism in the RES of liver and spleen must exclude extrahepatic causes of hyperbilirubinemia

Serum Albumin Level  

detects prolonged (weeks) hepatic dysfunction must exclude malnutrition and renal or GI losses, acute illness

Clinical Pearl All clotting factors except factor VIII are exclusively synthesized in the liver. Clinical Pearl Order of deterioration of Liver Function Tests: 1. increased PT/INR 2. increased bilirubin 3. decreased albumin  increased AST, ALT = hepatocellular damage

Loren Warmington

ALT more specific to liver; AST from multiple sources o elevation of both highly suggestive of liver injury implies hepatitis (inflammation) or vascular injury (ischemia) if AST, ALT >1000, think of common bile duct stone, virus, drugs, ischemia, autoimmune hepatitis

 increased ALP with increased GGT = cholestatic disease    

biochemical cholestasis (drugs) systemic disease (e.g. sepsis), pregnancy infiltrative disease (tumour, fat, lymphoma) mass lesions (stone, tumour, abscess)

 Inflammatory (PBC, PSC) Clinical Pearl Serum transaminases >1000 due to • viral hepatitis • drugs • common bile duct stone • hepatic ischemia • rarely immune hepatitis Clinical Pearl AST > ALT (usually AST/ALT >2 and AST AST = viral hepatitis Clinical Pearl Risk of developing infection from needle puncture HBV 30% HCV 3% HIV 0.3%

Specific Drugs Figure 14. Time Course of Acute Hepatitis B Infection

Chronic Hepatitis 

an increase in serum transaminases for >6 months; requires a liver biopsy to determine severity/need of treatment

Etiology     

viral (B, B+D, C, not A or E) drugs (methyldopa, INH, nitrofurantoin, amiodarone) autoimmune genetic (Wilson’s disease, alpha1antitrypsin deficiency) metabolic (nonalcoholic steatohepatitis: NASH)

Clinical Features      

often asymptomatic, detected incidentally constitutional symptoms fatigue, malaise, anorexia, weight loss signs of chronic liver disease hepatomegaly (firm) and splenomegaly increased AST, ALT

Drug induced Liver Disease


acetaminophen o metabolized by hepatic cytochrome P450 system o can cause fulminant hepatic failure (transaminases >1,000 U/L) o requires 10-15 g in normals, 4-6 g in alcoholics/anticon vulsant users o recent studies have emphasized liver disease in chronic users >4 g/day o mechanism: high acetaminophen dose saturates glucuronidation and sulfation eliminati on pathway --> reactive metabolite is formed --> covalently binds to hepatocyte membrane presentation o first 24 hrs: nausea and vomiting usually within 4-12 hours o next 24-48 hrs: hepatic necrosis resulting in increased aminotransferase s, jaundice, possibly hepatic encephalopathy, acute renal failure, death o after 48 hrs: continued hepatic necrosis/resolutio n o note: potential delay in presentation in

Loren Warmington

sustained-release products o blood levels of acetaminophen correlate with the severity of hepatic injury, particularly if time of ingestion known therapy o gastric lavage/emesis (if
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