Pathophysiology of Sodium Handling

Question 1

Effective arterial blood volume definition

Answer 1

• =volume of blood detected by volume sensors @ arteries
• arterial blood volume required to “fill” the capacity of arterial circulation

Question 2

Types of volume sensors

Answer 2

• low-pressure baroreceptors
• high-pressure baroreceptors
• intrarenal sensors
• hepatic and CNS sensor

Question 3

Characteristics of low-pressure baroreceptors

Answer 3

• include: cardiac atria receptors, left ventricular receptors, pulmonary vascular bed receptors
• located @ venous side of circulation
• protect against ECF volume expansion/contraction
• expansion stimulation ==> decreased renal sympathetic nerve activity ==> net loss of sodium and water

Question 4

Characteristics of high-pressure baroreceptors

Answer 4

• carotid sinus body @ bifurcation of carotid
• aortic body @ aortic arch
• located @ arterial side + protect against volume contraction and expansion
• maintain MAP and protect vital organs from fluctuations
• volume contraction ==> increased renal sympathetic nerve activity ==> anti-natriuresis + anti-diuresis

Question 5

Characteristics of intrarenal volumes sensors

Answer 5

• formed by renal JGA (<== releases renin)
• renin release influenced by:
  
  • changes in renal perfusion pressure
  • NaCl delivery to JGA
  • renal sympathetic nerves

Question 6

Kidney effectors of fluid volume homeostasis

Answer 6

• glomerular filtration
• physical forces @ proximal tubule
• humoral effectors
  
  • AgII, aldosterone, catechlamines ==> salt retention
  • Pgs, bradykinin, ANP ==> natriuresis
• renal sympathetic nerves
  
  • innervate afferent & efferent arterioles
  • stimulated in volume contract ==> sodium conservation
  • enha

Question 7

Regulatory mechanisms of glomerular filtration

Answer 7

• renal autoregulation
• tubuloglomerular feedback (TGF) = NaCl ==> macula densa ==> increased afferent arteriolar tone
• glomerulo-tubular balance = GFR changes ==> proportional change in rate of proximal tubular sodium reabsorption

Question 8

Major sodium transport channel/mechanism @ proximal tubule, TALH, Distal tubule, collecting duct

Answer 8

• proximal tubule = Na/K ATPase, Na/H Antiporter, Carbonic anhydrase
• TALH = Na/K/2Cl cotransporter
• Distal tubule = Na channels, Na/Cl co-transporter, Na/H antiport
• collecting duct = @ principal cells: via Na channels in exchange for K

Question 9

Renal response to extracellular volume contraction

Answer 9

• Decreased GFR resulting in a smaller filtered load of sodium.
• Activation of the renal sympathetic nerves ==> vasoconstriction of the afferent arteriole (decreases GFR) + increased tubular re-absorption of sodium.
• Decreased hydrostatic pressure and increased oncotic pressure in the peritubular capillaries = enhance fluid reabsorption into the peritubular capillaries.
• Stimulation of renin-angiotensin-aldosterone system.
• Increased secretion of ADH ==> increased water reabsorption @ collecting duct
• Inhibited secretion of atrial natriuretic peptide (ANP) from the atrial myocytes.

Question 10

Common signs/sx of volume contraction

Answer 10

• thirst, postural dizziness, weakness
• confusion, decreased urine output
• weight changes
• orthostatic hypotension**
• tachycardia
• decreased CVP, RA pressure, PCWP, CO + increased systemic vascular resistance

Question 11

Serum indication of volemic contraction

Answer 11

• Increased BUN (comes w/Na reabsorb)
• Metabolic alkalosis = upper GI loss of fluid
• Metabolic acidosis = lower GI loss of fluid
• increased heatocrit + albumin

Question 12

Tx of extracellular volume contraction

Answer 12

• acute hemorrhage = give blood or plasma volume expanders e.g. albumin or dextran ==> preferentially expand intravascular volume
• Isotonic normal saline (0.9% NaCl) ==> prefentially expands ECF (also expands IV volume)
• D5W ==> expands intracell and extracell fluids

Question 13

Main types of pathophysiology ==> extravascular volume expansion

Answer 13

1. distrubed starling forces ==> reduced effective arterial volume
   
   1. CHF
   2. nephrotic syndrome
   3. cirrhosis
2. primary hormone excess
   
   1. primary hyperaldosteronism
   2. cushing’s syndrome
   3. SIADH
3. primary renal sodium retention
   
   1. acute glomerulonephritis

Question 14

Formation/maintenance of edema

Answer 14

• decrease in capillary oncotic pressure and/or
• increase in capillary hydrostatic pressure ==.
• edema from fluid flowing out of capillaries and into ECF
• baroreceptors maintain edema via perceived reduced effective arterial circulating volume
• arterial underfilling ==> stimulates kidney to retain sodium + water

Question 15

Pathogenesis of CHF

Answer 15

• edema due to increased filling pressures + reduced CO ==> decreased flow to arterial sensors

Question 16

Pathogenesis of Nephrotic Syndrome

Answer 16

• hypoalbuminemia ==> fall in capillary oncotic pressure
• ==> edema + fall in effective arterial blood volume
  
  • commonly leg and face swelling or diffuse

Question 17

Pathogenesis of cirrhosis

Answer 17

• intrahepatic hypertension + portal hypertension + splachnic vasodilation + hypoalbuminemia ==> decreased effective arterial pressure

Question 18

Tx of extracell volume expansion

Answer 18

• treat underlying condition
• salt restriction
• diuretics

Question 19

Common diuretics @ proximal tubule

Answer 19

• acetazolamide ==> blocks carbonic anhydrase ==> wastage of bicarbonate in urine
• weak diuretic
• tx: metabolic alkalosis w/volume overload

Question 20

Common diuretics @ LOH

Answer 20

• furosemide, bumetanide, torsemide
• inhibit Na/K/2Cl transport @ apical membrane
• potent diuretic
• side effects: met alkalosis, hypokalemia, hypocalcemia, hypomagnesemia

Question 21

Common diuretics @ distal tubule

Answer 21

• thiazide diuretics
• inhibit NaCl transporter @ apical membrane
• side effects: met alk, hypokalemia, hypomagnesemia

Question 22

Common diuretics @ collecting duct

Answer 22

• tramterene, amiloride
• spironoactone = competitive inhibitor of aldosterone
• potassium-sparing diuretics (help prevent hypokalemia)