Renal Physiology

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Increase ADH

PHYSIO B 1.2 RENAL PHYSIOLOGY PT. 4 [DR. VILA] FEU-NRMF INSTITUTE OF MEDICINE 11.11.14 [1MD-D]

Increase water reabsorption Disorders of Urinary Concentrating Ability Impairment in the ability of the kidneys to concentrate or dilute the urine appropriately can occur with one or more of the following abnormalities: 1. Inappropriate secretion of ADH 2. Impairment of the countercurrent mechanism. A hyperosmotic medullary interstitium is required for maximal urine concentrating ability. No matter how much ADH is present, maximal urine concentration is limited by the degree of hyperosmolarity of the medullary interstitium. 3. Inability of the distal tubule, collecting tubule, and collecting ducts to respond to ADH Failure to produce ADH: “Central” Diabetes Insipidus  Also known ad pituitary diabetes insipidus  Hypothalamus or posterior pituitary gland fails to produce or secrete ADH  Large volumes of dilute urine (can exceed 15L/day) Inability of the kidneys to respond to ADH: “Nephrogenic” Diabetes Mellitus”  Normal or elevated levels of ADH are present  But renal tubules cannot respond  Can be caused by: o Failure of countercurrent mechanism (Guyton) o Failure of distal and collecting ducts to respond to ADH (Guyton) o Absence of V2 receptors for ADH (Accdg. to Dr.Vila)  Large volumes of dilute urine  Can cause dehydration, unless fluid intake is increased by the same amount as urine volume is increased Diabetes: common manifestation is polyuria  Diabetes insipidus: secondary to ADH deficiency  Diabetes mellitus: secondary to glucose No ADH Secretion / No response to ADH

Decrease reabsorption of water

Decrease urine volume

Increase urine tonicity

Supposedly. Because of increase water reabsorption:

Increase BV

Increase BF

Increase GFR

Increase urine volume  

Initially, there is an increase in water reabsorption Eventually, the end effect will be an increase in urine excretion due to increase blood volume Osmoreceptor-ADH Feedback System  Example: Increase plasma osmolarity due to dehydration o Fluid shift from the interstitium into the intravascular compartment o Osmoreceptors are located in the anterior hypothalamus near the supraoptic nuclei [Guyton] o Osmoreceptors are sensitive to changes in osmolarity o An increase in extracellular osmolarity will cause the osmoreceptors to shrink o Sends signals to the hypothalamus to secrete ADH o ADH enters blood stream towards the kidneys to increase water reabsorption and decrease urine volume

Increase Urine Volume

Decrease urine tonicity The Syndrome of Inappropriate ADH Secretion (SIADH)  Plasma ADH elevated (as in sobrang taas, above what would be expected on the basis of the body fluid osmolality and, blood volume and pressure, kaya siya “inappropriate”)  Water is retained, hence body fluid becomes hypoosmotic (more water, less concentrated ang body fluids)  Urine is hyperosmotic  The tonicity of plasma decreases due to dilutional hyponatremia  However, the amount of sodium still falls within normal range  It appears to be hyponatremic due to the increase in water reabsorption (dilution) Prepared by: Mar Mariano

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Edema 

Excess fluid within the interstitial compartment producing visible swelling  Increased capillary hydrostatic pressure  Decreased plasma colloid osmotic pressure Edema caused by Heart Failure [Guyton, Chp. 25]  One of the most serious and most common causes of edema  In heart failure, the heart fails to pump blood normally from veins into the arteries, which raises the venous and capillary pressures, which eventually increases capillary filtration  Increase capillary filtration  lalabas ang fluid sa interstitium  edema  Heart failure can also decrease blood flow to the kidneys  Decrease blood flow  decrease Na+ concentration  detected by macula densa  secrete renin by JG cells  activate angiotensinogen to angiotensinogen I  conversion to angiontensin II by ACE in lungs  release aldosterone  Increase salt and water retention  Increase BV  Increase capillary hydrostatic pressure  Increase hydrostatic pressure  edema Edema caused by Decreased Plasma Proteins [Guyton, Chp. 25]  One of the most important causes of decreased plasma protein concentration is loss of proteins in the urine – Nephrotic syndrome  The glomerular basement membrane widens, that allows the filtration of proteins  Protein will therefore appear in the urine – Proteinuria  Therefore, there will be a decrease in plasma proteins  Decrease plasma protein decrease plasma colloid osmotic pressure  edema Lymphedema – Failure of the Lymph Vessels to return fluid and protein to the blood [Guyton, Chp. 25]  Plasma proteins tend to leak into the interstitium, which can attract water and eventually cause edema  The proteins be removed through the lymphatics  Example of lymph obstructions are infections with filaria nematodes (Wuchereria bancrofti) o Blocks lymph vessels o Causes lymphedema and elephantiasis o Localized edema (limited to a one area only, [ex.] Extremities, penis, breast) Localized Edema 1. Venous obstruction 2. Capillary was damaged due to inflammation 3. Lymphatic obstruction Generalized Edema 1. Increase capillary hydrostatic pressure 2. Decrease plasma albumin  Clinical Findings: o Swelling in most dependent parts of the body due to effects of gravity and increase hydrostatic pressure in the capillaries Edema vs. Effusion  Edema: fluid in interstitum  Effusion: fluid in potential spaces – pleural, peritoneal, pericardial cavities, joint spaces Effect of Adding Saline Solution to the ECF [Guyton, Chp. 25]  Principle of osmosis  If a cell is placed in a hypotonic solution, the cell will swell (movement of water from extracellular to intracellular)  However, the cell will not swell immediately

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The cell will try to pump out electrolytes such as Na+, so that water will follow these electrolytes out of the cell and reduce swelling This is called regulatory volume decrease (decrease cell volume to reduce swelling) If a cell is placed in a hypertonic solution, the cell will shrink, but not immediately (movement of water intracellular to extracellular) Electrolytes from the solution will move into the cell, and water will follow, hence reducing the shrinkage of the cell This is called regulatory volume increase (increase cell volume to reduce shrinkage)

Fluid INFLUX Isotonic Influx (2L NSS) Hypotonic Influx (Water loading)

Hypertonic Influx (Drink sea water)

ECF Vol.

ECF OP

H2O Shift

ICF Vol.

ICF OP

Compensatory Mechanism

SA ME

NONE

SA ME

SA ME

NONE

Extra to intrace llular

Intra to extrac ellular

-Decrease ECF tonicity -Activate ADH -Water reabsorbed -Decrease urine volume -Increase urine tonicity -Increase ECF tonicity -Inhibit ADH -Increase urine volume -Decrease urine tonicity

Prepared by: Mar Mariano

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Fluid EFFLUX Isotonic Efflux (Burns) Hypotonic Efflux (Profuse Sweating)

Hypertonic Efflux (SIADH)

ECF Vol.

ECF OP

H2O Shift

ICF Vol.

ICF OP

Compensatory Mechanism

SA ME

NONE

SA ME

SA ME

NONE

Intra to extrac ellular

Extra to intrace llular

-High ECF tonicity -Activate ADH -Water reabsorption -Decrease urine volume -Increase urine tonicity -Low ECF tonicity -Inhibit ADH -Increase urine volume -Decrease urine tonicity

Acid-Base Balance  Acid: a substance that can release or donate hydrogen ion [H+]  Base: a substance that can combine with or accept hydrogen ion [H+]  Normal blood pH: 7.35 – 7.45  Normal pCO2: 35 – 45 mmHg  Normal pCO3-: 22 – 26 mmHg  pO2 is less important *Respi Physio Review* Oxygen-Hemoglobin Dissociation Curve

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Hemoglobin carries oxygen However, hemoglobin never reaches 100% oxygen saturation. Why? o All the blood that reaches the lungs will be 100% oxygenated o From the lungs, and along with the blood from different veins, will drain into the heart o Veins carry less oxygenated blood o Blood that comes out of the aorta will only be 9798% saturated with oxygen because it will be mixed with less oxygenated blood from the veins o At 60mmHg, the saturation slows down o Below 60mmHg, saturation is steep (Hgb unbinds immediately from oxygen) o In real situations, we never go below 60mmHg

o

o

  Rules:  

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pCO2: respiratory component o Represent acid o Excreted by lungs o Increase pCO2: Acidic o Decrease pCO2: Basic pCO3-: metabolic component o Represent base o Excreted by kidneys o Increase pCO3-: Basic o Decrease pCO3: Acidic Decrease pH: acidosis Increase pH: alkalosis Always follow the pH If fully compensated: pH will go back to normal o If pH is slightly toward alkaline but within normal range: alkalosis, fully compensated o If pH is slightly toward acidic but within notmal range: acidosis, fully compensated If partially compensated: pH of blood is still abnormal pCO2

pH

(35 – 45 mmHg)

(7.35 – 7.45)

pCO3(22 -26mmHg)

7.29

Acidic

48

Acidic

24

Normal

7.29

Acidic

37

Normal

19

Acidic

7.47

Basic

32

Basic

24

Normal

7.47

Basic

37

Normal

29

Basic

7.29

Acidic

36

Normal

19

Acidic

7.47

Basic

32

Basic

19

Acidic

7.47

Basic

48

Acidic

29

Basic

7.29

Acidic

30

Basic

28

Basic

7.47

Basic

30

Basic

19

Acidic

7.44

Normal

48

Acidic

30

Basic

7.38

Normal

48

Acidic

30

Basic

Disorder Respiratory Acidosis Metabolic Acidosis Respiratory Alkalosis Metabolic Alkalosis Metabolic Acidosis Respiratory Alkalosis, partially compensated by the kidneys Metabolic Alkalosis, partially compensated by lungs Mixed Acidosis, partially compensated Respiratory Alkalosis, partially compensated Metabolic Alkalosis, fully compensated Respiratory Acidosis, fully compensated

Prepared by: Mar Mariano

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Kidneys o Third line of defense o Remove excess H+ from the body in combination with urinary buffers Henderson-Hasselbach Equation  Shows that the pH of a solution is determined by the pKa of acid and the ratio of the concentration of conjugate base Aand acid HA Bicarbonate Buffer System: Kidneys [Berne&Levy Chp. 36]

pH Units  In the events of everyday life, the variation of ECF pH is very narrow  1nmol of H+/L = 0.01 pH unit o If H+ ions increase: pH decrease, pH is acidic o If H+ ions decrease: pH increase, pH is basic  In abnormal situations, much wider changes may be seen.  In practice, a pH of 6.8 or 7.8 will only be seen in profound pathologic situations Sources of H+ ions in the body  Metabolism of food stuffs o Produces 300L of CO2  Incomplete metabolism of CHO and fats o Produces nonvolatile acids o Lactic acid from glucose, acetoacetic acid and Beta-hydroxybutyric acid from fatty acid oxidation  Oxidation of proteins and amino acids o Produces strong acids o H2SO4, HCl and H3PO4 Body’s defenses against changes in blood pH  Chemical buffers in ECF, ICF and bone o First line of defense of blood pH o Minimized a change in pH but cannot remove acid or base from the body  Respiratory system o Second line of defense o Large loads of acid stimulate breathing which removes CO2 from the body

 The most important ECF buffer In the proximal tubules:  The proximal tubule reabsorbs the largest portion of the filtered load of HCO3 H+ secretion across the apical membrane of the cell occurs by Na+H+ antiporter and H+-ATPase  Carbonic anhydrase are present in the brush borders that convert H2CO3 to water and carbon dioxide  They enter the cells and combines to produce H+ and HCO3 by carbonic anhydrase  H+ is secreted via apical membrane, HCO3- via basolateral membrane  HCO3 exit via a symporter: 1Na+ with 3HCO3  Some of the HCO3 may exit in exchange for Cl A K+-HCO3- symporter in the basolateral membrane may also contribute to the exit of HCO3- from the cell

In the collecting ducts  There are 2 types of cells: o Principal cells responsible for electrolyte and fluid absorption o Intercalated cells for acid-base balance  There are 2 types of intercalated cells o Alpha-intercalated cells: secrete H+ (reabsorbs HCO3-) o Beta-intercalated cells: secrete HCO3 Within Alpha-intercalated cells: o H+ and HCO3- are produced by the hydration of carbon dioxide, which is catalyzed by carbonic anhydrase Prepared by: Mar Mariano

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o

H+ is secreted into the tubular fluid via:  Apical membrane H+-ATPase  H+,K+-ATPase o HCO3- exits across the basolateral membrane in exchange for Cl-, via a Cl-HCO3- antiporter o Active during metabolic acidosis  Within Beta-intercalated cells o H+-ATPase is located in the basolateral membrane o Cl-HCO3- antiporter is located in the apical membrane [Baliktad sila ng alpha-intercalated] o Activity of beta-intercalated cells is increased during metabolic alkalosis, when the kidneys must excrete HCO3Acid-Base Balance via excretion of ammonium  NH4+: ammonium, acidic  NH3: ammonia  NH4+ is produced by the kidneys by the metabolism of glutamine  The kidneys metabolize glutamine, excrete NH4+, and add HCO3- to the body  If NH4+ is not excreted in the urine, it is converted into urea by the kidneys, which produces H+, and eventually buffered by HCO3 Production of urea, therefore, consumes HCO3- and inhibits HCO3- formation through the synthesis and excretion of NH4+

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NH4+ is produced from glutamine via ammoniagenesis One glutamine molecule produces two NH4+ molecules and two HCO3- molecules HCO3- exits the cells across the basolateral membranes and enters the peritubular blood NH4+ exits via apical membrane and enters the tubular fluid, via NA+-H+ antiporter, but NH4+ is substituted for H+ NH3 is freely permeable and can diffuse out of the cell where it is protonated into NH4+ The thick ascending limb is the primary site of NH4+ reabsorption, with NH4+ substituting for K+ on the 1Na+K+-2Cl- symporter

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The NH4+ that is reabsorbed, accumulates in the medullary interstitium which is then secreted into the collecting ducts via: o Nonionic diffusion o Diffusion trapping NH3 diffuses from the medullary interstitium into the collecting ducts (nonionic diffusion) The presence of Alpha-intercalated cells which secrete H+ ions will protonate the NH3 to become NH4+ Since NH4+ is less permeable in the collecting ducts, it is trapped in the tubular lumen (diffusion trapping) It is then eliminated from the body via the urine

Please refer to Guyton for the Phosphate Buffer System and Proteins as ICF buffers, and Guyton Chp. 36 Acid-Base Balance (Hindi na diniscuss ni doc, pero kasama daw sa shifting ) Reading assignments:  Renal Failure  Renal Endocrine Function

Sources: Lecture: Dr. Vila Berne&Levy, 6th Edition Guyton and Hall, 12th Edition

Read Berne & Levy or Guyton, guys! Mas specific at complete mga explanations dun. Good luck and God bless! Labyu all