Regulation of Extracellular Fluid Volume

Question 1

What is hyovolemia?

How does the body sense hyopvolemia?

What is the body’s response to each of these receptors?

Answer 1

• Hypovolemia
  
  • decreased effective circulating volume
• Sensed
  
  • Intrarenal baroreceptor-
    
    • afferent arteriole (juxtaglomerular cells)
    • release renin
  • Cardiopulmonary baroreceptors
    
    • high pressure (carotid sinus & aortic arch)
    • low pressure receptors (right atrium & ventricle)
    • increase sympathetic output
  • Tubuloglomerular feedback (autoregulation
    
    • high distal nephron flow and high NaCl
      
      • macula densa releases adenosine that inhibits renin release & causes afferent arteriolar vasoconstriction that decreases GFR
    • low distal nephron flow and low NaCl
      
      • macula densa release NO (and PGE2) that causes afferent arteriolar vasodilation that increases GFR

Question 2

What are the actions of angiotensin II?

Answer 2

Major Goal: Restore Effective Circulation Volume

• Vasoconstriction
  
  • Peripheral vessels: increases arterial pressure
  • Renal arterioles: constriction of both afferent and efferent arterioles, and decreases renal blood flow and GFR, and reduces excretion of sodium
• Increases Na⁺ reabsorption
  
  • Proximal tubule: stimulates na-K-ATPase and activity of NHE3 (Na⁺-H⁺ exchanger)
  • Distal nephron: stimulates Na-Cl co-transport (NCC) and endothelial Na⁺ channels (ENAC)
• Stimulates aldosterone secretion from adrenal cortex
• Stimulates intake & thirst
  
  • hypothalmic

Question 3

What are the actions of aldosterone?

How quickly is its onset?

Answer 3

• Stimulates Na⁺ reabsorption in principal cells; and causes
  
  • K⁺ secretion (Principal cells)
  • Cl^- reabsorption (paracellular)
  • H⁺ secretion (intercalated cells)
• Latency is ~90 min (slow)

Question 4

Aldosterone can increas Na⁺ by how much?

Answer 4

about 3%

fine control of Na⁺ excretion

Question 5

What are the primary stimuli for aldosterone release?

What factors suppress aldosterone release?

Answer 5

• Primary stimuli for release
  
  • Angiotensin II (increases in hypovolemic statess)
  • Hyperkalemia - extremely snsitive; direct effect of K⁺ on zona glomerulosa cells of the adrenal cortex
• Suppressed by (high volume states):
  
  • ANP
  • BNP
  • Dopamine

Question 6

How do changes in GFR alter Na⁺ excretion?

Why?

Na⁺ reabsorption is dependent on what variable?

Answer 6

• Increase in GFR increases Na⁺ excretion
• Decrease in GFR decreases Na⁺ excretion
• Changes in GFR change hte filtered load of Na⁺ and other solutes that are coupled to Na⁺ reabsorption
  
  • Na⁺ reabsorption is load-dependent in the different nephron segments

Question 7

What is the autoregulatory response when the macula densa senses an increase in flow and an increase in Na⁺ delivery?

What is the autoregullatory response when the macula densa senses a decrease in flow and a decease in Na⁺ delivery?

Answer 7

• Increase
  
  • ATP (adenosine) released by Macula Densa
    
    • decreased GFR (maintains normal filtered load)
    • decreased renin secretion (allows more Na⁺ excretion)
• Decrease
  
  • No & Prostaglandins released by Macula Densa
    
    • increased GFR (maintains normal filtered load)
    • increased renin secretion (conserve body Na⁺)

Question 8

What are the responses to a hypovolemic state?

Answer 8

• GFR
  
  • decrease
• Sympathetic activity
  
  • increase
• Angiotensin II
  
  • increase
• Aldosterone
  
  • increase
• Prostaglandins
  
  • increase
• Na⁺ excretion
  
  • decrease

Question 9

What are the responses to a hypervolemic state?

Answer 9

• GFR
  
  • increase
• ANP & BNP
  
  • increase
• Urodilatin
  
  • increase
• Na⁺ excretion
  
  • increase

Question 10

What cells release ANP & what is the stimulus to do so?

What are the systemic effects of ANP

Answer 10

• Atrial Natriuetic Peptide (ANP)
  
  • Released by myocytes in the right atria in response to stretch (perceived as hypervolemia)
• Effects
  
  • afferent arteriolar vasodilation (increase GFR and decrease FF)
  • decreases peritubular capillary reabsorption
  • inhibits Na⁺ reabsorption (natriuresis) in the collecting tubules, causing diuresis
  • inhibits aldosterone secretion

Question 11

What cells release BNP & what is the stimulus to do so?

What are the systemic effects of BNP?

Answer 11

• Brain (B-type) Natriuetic Peptide
  
  • originally found int he brain
  • released from myocytes in the right ventricle in reponse to stretch
• Effects (similar to ANP)
  
  • afferent arteriolar vasodilation (increase GFR and decrease FF)
  • decreases peritubular capillary reabsorption
  • inhibits Na+ reabsorption (natriuresis) in the collecting tubules, causing diuresis
  • inhibits aldosterone secretion

Question 12

Where is urodilatin produced & what is its function?

Answer 12

• Produced in the distal nephron
  
  • intrinsic renal hormone
• Function
  
  • inhibits Na⁺ and water reabsorption in medullary collecting duct
  • levels show strong correlation with natriuresis (excretion sodium in urine)

Question 13

Do cortical nephrons or juxtamedullary nephrons have a lower capacity for Na⁺ and water reabsorption?

Why?

Flow is shunted toward what type of nephron in hypervolemic state? hypovolemic state? Mechanism?

Answer 13

• Cortical nephrons hav ea lower capacity for Na⁺ and water reabsorption due to shorter loops of Henle
• Hypervolemic state
  
  • ​shunted toward cortical nephrons (increases Na⁺ and H₂O excretion)
• Hypovolemic state
  
  • shunted toward juxtamedullary nephrons (decreases Na⁺ and H₂O excretion)
• Mechanism of shunting: Angionensin II causes greater vasoconstriction in cortical afferent arterioles

Question 14

What are the effects of norepinephrine and angiotensin II in low volume states?

Net effect?

Answer 14

• Norepinephrin & Angiotensin II
  
  • peripheral vasoconstriction which increases arterial pressure (effective circulating volume)
  • stimulate Na⁺ reabsorption in proximal tubule
• Angiotensin II
  
  • stimulates the Na⁺- H⁺ exchanger in the proximal tubule by increasing Na-K-ATPase activity
  • stimulate Na⁺ reabsorption in distal tubule
• Net effect: increased solute & water reabsorption

Question 15

An increase in arterial pressure has what impact on urine?

This relationship is probably due to what hormone?

Answer 15

• Perfusion pressure dependent natriuresis and diuresis
  
  • increased arterial pressure is correlated with increased urine sodium & volume output
  • Intrinsic mechanism: probably involves urodilatin

Question 16

What is the effect on glomerular capillaries & peritubular capillaries during efferent arteriolar vasoconstriction?

What about during vasodilation?

Answer 16

• Vasoconstriction (hypovlemia)
  
  • Glomerular Capillary:
    
    • keeps P_G from falling too much and increases filtration fraction
    • filtering relatively more from that golmerular capillary volume
  • Peritubular Capillary:
    
    • decreases P_C and increases π_P (increases reabsorptive capacity)
• Vasodilation (hypervolemia)
  
  • Glomerular Capillary:
    
    • increases P_G and decreases filtration fraction
  • Peritubular Capillary (where we see back-leak)
    
    • incrases P_C and decreases π_P (decreases reabsorptive capacity)

Question 17

What is osmotic diuresis?

What effect can it have on Na⁺ excretion?

Answer 17

When you have a lot of non-absorbable material that has been filtered into the tubule & it exerts an osmotic effect

the osmotic effect retains water & therefore increases Na⁺ excretion

Question 18

What impact do the following conditions have on Na⁺ excretion?

Impermeant anions in filtrate (diffusion drapped)?

Aldosteron excess?

Aldosteron deficit?

Answer 18

• Increase Na⁺ excretion
  
  • Impermeant anions in filtrate (diffusion trapped)
  • Aldosterone deficit
    
    • hypovolemia (not absorbing Na⁺)
    • hyperkalemia (not excreting K⁺)
    • metabolic acidosis (not excreting H⁺​)
• Decrease Na⁺ excretion
  
  • Aldosterone excess
    
    • hypervolemia (absorbing Na⁺ in excess)
    • hypokalemia (excreting K⁺ in excess)
    • metabolic alkalosis (excreting H⁺ in excess)

Question 19

What is the body’s response to hyper-aldosteronism?

Answer 19

• “Aldosterone escape” - diuresis that opposes excess Na⁺ and water retention
  
  • ANP, urodilatin, and pressure natriuesis?
  • After a period of time with hyper aldosterone, the aldosterone loses its effect & we stop reabsorbing as much Na⁺ and therefore losing as much K⁺ & H⁺

Question 20

What are the effects of eating a high Na⁺ meal?

What about a low Na⁺ meal?

Answer 20

• High Na⁺ intake
  
  • “positive Na⁺ balance”
    
    • Na⁺ reabsorption is greater than excretion
  • water rentention (increased ECBV)
    
    • fluid / weight gain
• Decreased Na⁺ intake
  
  • “negative Na⁺ balance”
    
    • Na⁺ excretion is greater than Na⁺ reabsorption
  • water elimination (decreased ECBV)
    
    • fluid / weight loss

Question 21

How does the body perceive being immersed in water?

What is the effect on Na⁺ excretion?

How long does this take?

Answer 21

• Redistribution of the intravascular volume (same as zero G)
  
  • perceived as hypervolemia
• Response
  
  • increase Na⁺ and water excretion
  • long latency (hours)

Question 22

Why is heart failure perceived as hypovolemia?

Answer 22

• Heart Failure leads to decreased Cardiac Ouptut
  
  • this leads to a decrease in ECBV which the body perceives as hypovolemia & responds with Na⁺ and water retention
  • This Na⁺ and water retention increases ECBV, which increases venous pressure, caues edema and the ECBV again decreases
• Viscious circle because the pump is not able to maintain the effective circulating blood volume
• The ECBV is perceived as hypovolemia even though extracellular volume is dramatically increased

Question 23

Why can cirrhosis & Nephrotic syndrome cause edema?

Answer 23

• Cirrhosis (decrease in production of plasma proteins)
• Nephrotic Syndrome (inflammation of glomerular capillaries and loss of protein in urine)
• In both cirrhosis & nephrotic syndrome, there is a decrease in plasma protein concentration, which leads to a decrease in plasma oncotic pressure, so fluid leaves the plasma and enters the interstitial space via osmosis, causing edema
  
  • the movement of water from the plasma to the interstitial space causes a decrease in ECBV, which the body responds to by increasing Na⁺ and water retention, again diluting the plasma and leading to further edema

Question 24

What system control long-term regulation of pressure?

What system regulations the moment-to-monent regulation of pressure?

Answer 24

• Long-term
  
  • Kidney sets arterial pressure at ~100mmHg by controlling the reabsorption and excretion of Na⁺ (which contorls water reabsorption & regulations ECBV)
• Moment-to-moment
  
  • baroreceptors respond rapidly to short-term change in pressure, utilizing the autonomic systems

Question 25

What are the 4 systemic factors that influence volume regulation?

Answer 25

1. Sympathetic activity
2. Circulating catecholamines
3. Angiotensin II
4. ANP and BNP

Question 26

What are the 8 factors that regulate renal Na⁺ excretion?⁺

Answer 26

Renal Na⁺ excetion

1. Sympathetic activity
   
   • affects GFR
   • increase reabsorption Na⁺ in proximal tubule
2. Changes in GFR
   
   • changes filter load of Na⁺
   • influences absorptive capacity peritubular capillaries
3. Angiotensin II
   
   • causes increases of Na⁺ absorption in the proximal tubule, distal convoluted tubule, & stimulates aldosteron release
4. Peritubular capillary hemodynamics
5. Aldosterone
   
   • increases Na⁺ reabsorption in the collecting ducts
6. ANP, BNP, and uridilin
   
   • inhibit Na⁺ excretion
7. Pressure natriuresis
   
   • leads to pressure diuresis & inhibits Na⁺ excretion
8. Plasma Na⁺ concentration – ADH
   
   • changes water excretion which changes Na⁺ concentration

Question 27

Go ahead and draw this out