05: Volume Regulation

Question 1

Total water space

Answer 1

• 60% body weight
• 40% is intracellular (mainly muscle cells)
• 20% is extracellular (volume)
  
  • 1/3 vascular/blood fluid
  • 2/3 interstitial fluid
• Extracellular fluid = 1L water + 135-145mEq Na+
• Na is regulator of extracellular volume

Question 2

Influence of NaCl/water on body volume

Answer 2

• ↑ extracellular volume
• Leads to ↑ weight, BP, organ perfusion

Question 3

Influence of Na+ alone on body volume

Answer 3

1. Osmotic shift of water into extracellular fluid 2/2 ↑Na+
2. ADH is released from posterior pituitary 2/2 ↑Na+ (↑plasma osmotic pressure) –> ↑aquaporin in CD
3. Thirst is induced 2/2 ↑Na+ (↑plasma osmotic pressure)

Question 4

Influence of water on body volume

Answer 4

Results in decreaed osmolarity

1. Water distrubutes EC and IC
2. Decreased thirst –> ↓water intake
3. ADH suppression –> ↑water excretion

Question 5

Causes of volume depletion

Answer 5

1. Vomiting
2. Diarrhea
3. Sweat (fever or exercise)
4. Not eating
5. Hemorrhage
6. Adrenal insufficiency
7. Diuretics
8. High urine flow (glucosuria)

Question 6

Symptoms & signs of volume depletion

Answer 6

• Symptoms
  
  • Light-headed
  • Weak, tired
  • Cold extremities
  • Thirst
• Constitutional signs
  
  • Low BP, orthostasis
  • Weight loss
  • Dry skin/no sweating/no saliva
  • Loss of skin turgor (elasticity)
• Kidney signs
  
  • Elevated BUN/creatinine ratio
  • Low urine Na+
  • Concentrated urine
  • Low urine volume

Question 7

Afferent limb to sense volume

Answer 7

1. Intrathoracic: LA, RA, RV, pulm caps
2. Arterial volume/baroreceptors: carotid & aortic arch
3. Renal artery baroreceptor: juxtaglomerular apparatus
4. CNS volume receptors
5. Hepatic volume receptors

Question 8

Function of granular cells

Answer 8

• Located within the juxtaglomerular apparatus on the afferent arteriole
• Release renin (2/2 volume depletion) into arteriole upon receiving stretch signal via beta adrenergic innervation (systemic control)
• Also release renin into arteriole upon receiving prostaglandin signal from macula densa cells in DCT (local control)

Question 9

Efferent control of ECFV in volume depletion

Answer 9

Volume depletion sensed by baroreceptors in CV system, signaling to CNS –>

1. Macula densa sensing a) sympathetic activation and b) prostaglandins leads to renin release –> ↑AII –> ↑aldosterone –> recovery of U_Na maximized in 2-3 days
2. Thirst and ↑**ADH **–> recover U_H2O
3. Salt appetite –> ↑Na+ intake

Question 10

Effects of angiotensin II

Answer 10

1. efferent constriction + Na transporters –> ↑PT reabsorption while maintaining GFR
2. vasoconstriction
3. ↑aldosterone –> ↑collecting duct reabsorption of Na
4. ↑excretion of H, NH₄, urea

Question 11

Diagnosis of volume depletion

Answer 11

• Plasma creatinine increases from baseline 0.9 —> 1.3 in prerenal dz
• As result of ↑AngII, ↑reabsorption BUN in proximal tubule –> elevation from 8-15 to 20-60
• BUN/Cr ratio nl = 10:1, but in prerenal dz may rise to >20:1 as result of AngII activity
• Fractional excretion of Na measures AII/ALD activity
  
  • (U_Na/P_Na) / (U_Cr/P_Cr)
  • U_Na/P_Na is a measure of tubular function, but since U_Na is a concentration and not mass, necessary to correct for water in urine by measuring change in creatinine concentration
  • Normal FeNa = 0.95

Question 12

Summary of volume depletion

Answer 12

• Underfilled phenotype with weight loss
• High BUN/Cr ratio (>20:1)
• Low U_Na, low FeNa; low urine volume; high urine osmolarity

Question 13

Stage I vs. Stage II Effective Volume Depletion

Answer 13

• Stage I
  
  • Underfilled phenotype
  • High BUN/Cr
  • Low UNa, low FeNa
  • Low urine vol, high urine osm
• Stage II
  
  • Normalized phenotype
  • Normalized BUN/Cr
  • Normalized UNa and FeNa
  • Normalized urine vol, osm

Question 14

Causes of volume overload

Answer 14

• Unusual by simple ingestion
• Kidney failure (1* gain Na)
• CHF (2* gain Na)
• Cirrhosis (1*, 2* gain Na)
• Nephrosis (1*, 2* gain Na)
• Mineralocorticoid XS (1* gain Na)

Question 15

Symptoms & signs of extracellular volume overload

Answer 15

• Symptoms: SOB
• Signs:
  
  • ↑BP
  • ↑weight
  • edema (peripheral, pulmonary)
• Kidney:
  
  • Low/high urine vol (depending)
  • Low/high urine Na+ (depending)
  • Dilute urine

Question 16

Efferent control of ECFV in volume overload

Answer 16

• Volume expansion sensed by baroreceptors in CV system, signaling to CNS:
  
  • Macula densa sensing cardiac overload –> ANF –> ↑UNa, inhibition of renin, AII
  • Inhibited thirst, salt appetite

Question 17

RAAS response to volume overload

Answer 17

• Renin: no secretion
• ANF:
  
  • Afferent vasodilat –> ↑GFR (Na filtered)
  • ↓alodsterone –> ↓collecting duct reabs Na; ↑excretion H, NH4, urea
• No AII
  
  • Efferent dilation –> ↓PT reabs, maintained GFR
  • Vasodilation
• NE: ↓GFR
• No ADH: ↓reabs. H2O

Question 18

ANF

Answer 18

Dilates afferent, inhibits renin, for increased GFR –> same or less reabsorption in proximal tubule.

Question 19

AII

Answer 19

Constricts efferent, enhances activity of Na/H exchanger and NaKATPase in PT, for same GFR, increased reabs in PT

Question 20

Aldo

Answer 20

Enhances activity of Na channel in principal cell, K channel in principal cell, H+ATPase in intercalated cell

Question 21

ADH

Answer 21

Enhaces water reabs from principal cell and urea reabs from TALH

Question 22

NE

Answer 22

For decreased GFR, same reabs in PT