ECF Volume Regulation 2

Question 1

What protein is responsible for Na excretion at the distal tubule?

Answer 1

Atrial Natriuretic Peptide (ANP)

Question 2

What happens to a subject who is given aldosterone supplementation whilst on an adequate Na diet?

Answer 2

• First they will gain weight due to Na and water retention. They will also lose K in excess
• After a couple days they will experience spontaneous diuresis (excretion of Na & water), although K loss will still persist
  (ANP)

Question 3

What is Natriuresis? Where is ANP produced?

Answer 3

• Excretion of sodium & water in the urine

- ATRIAL natriuretic peptide (produced in the atria)

Question 4

What causes the secretion of ANP?

Answer 4

• Increased ECF volume

Question 5

What would you expect to find when looking at the bloods of a patient with Conn’s syndrome (hyperaldosteronism)?

Answer 5

Low K levels

Na would be normal due to ANP effects

Question 6

What are the functions of Natriuretic peptides?

Answer 6

• Inhibit ADH at hypothalamus
• Increase GFR and decrease renin at kidneys
• Decrease aldosterone secretion at adrenals
• Decrease BP at medulla

Question 7

How does hyperglycaemia, such as in uncontrolled DM, lead to hypovolaemia?

Answer 7

• The [glucose] exceeds the max reabsorptive capacity of the proximal tubule
• Glucose remains in the tubule and exerts an osmotic effect to retain water in the tubule
• The [Na] in the tubule is lower because there is more water in the tubule, and so it can’t diffuse into the tubule epithelium due to the decreased gradient
• Lack of Na reabsorption causes less glc reabsorption due to symport
• The excess Na & glc in the tubule reduce the flow of water out of the tubule in the desc. loop of Henle
• The retention of water in the desc. loop causes lower concentration filtrate in the ascending loop, since the NaCl pumps are gradient limited, can’t concentrate the interstitium
• Results in little water reabsorbed, large volumes of NaCl and water to the distal tubule, and the eventual loss of the interstitial gradient
• The macula densa detects high NaCl in the distal tubule and so suppresses renin, resulting in a decrease in Na reabsorption at the distal tubule

Question 8

How is glucose reabsorption affected in uncontrolled diabetes mellitus?

Answer 8

• High blood [glc] results in filtrate with [glc] that exceeds max resorptive capacity in proximal tubule
• Glucose exerts osmotic effect, tubule retains water
• More water = low Na gradient, Na can’t be transported out of the tubule
• Since glc & Na are symported, this results in even less glucose reabsorption

Question 9

How is water reabsorption affected in uncontrolled diabetes mellitus?

Answer 9

• High glucose stops water reabsorption in prox. tubule
• High Na & glc. stops water diffusing out into interstitium in desc. loop of Henle
• Reduced interstitial gradient results in less water being reabsorbed out of the collecting duct (ADH can’t work as well)

Question 10

How does uncontrolled diabetes mellitus affect the interstitial gradient?

Answer 10

• Higher Na & glc. in the descending loop means less water diffuses out = low conc. filtrate in asc. loop
• Since NaCl pumps in loop work via gradient, can’t pump out as much NaCl with less dilute filtrate
• If left unmonitored this eventually results in loss of interstitial gradient completely

Question 11

What symptoms / signs occur as a result of the effects of hyperglycaemia on the kidneys?

Answer 11

• Hypovolaemia (low BP)
• Glucosuria
• Polyuria
• Polydipsia

Question 12

How much urine is excreted in established uncontrolled diabetes mellitus?

Answer 12

6-8 Litres of isotonic urine per day

Question 13

Describe the pathophysiology of a hyperglycaemic coma

Answer 13

Uncontrolled hyperglycaemia leads to the development of hypovolaemia

• If the hypovolaemia is severe enough, blood flow to the brain can bee inadequate and coma can result

Question 14

What is osmotic diuresis?

Answer 14

• When a substrate in present in excess in the filtrate and causes the amount of water in the urine to increase due to osmotic effects

(glc is the substrate for this process in hyperglycaemia that leads to hypovolaemia)

Question 15

Is glucose the only substrate that can cause osmotic diuresis? Why is diabetes mellitus particularly bad in terms of osmotic diuresis?

Answer 15

• No, any substrate present in excess in the filtrate can cause osmotic diuresis
• DM is particularly bad because the liver will keep producing free glucose and so the problem is not self limiting, and will continue until the kidneys fail

Question 16

Why can the use of loop diuretics / being in a state of osmotic diuresis cause low potassium?

Answer 16

Because some of the transporters in the ascending loop of Henle are not just NaCl transporters, they also transport K with the NaCl

So disabling of these transporters would cause insufficient K reabsorption