Lecture 7 - ECF Volume Regulation 1 and 2

Question 1

What ions are the major ECF osmoles?

Answer 1

Na Cl

Question 2

What substance is the major ICF osmole?

Answer 2

K salts

Question 3

How is regulation of ECF volume carried out?

Answer 3

By regulating body Na

Question 4

Describe the total distribution of body water between: Plasma Interstitial fluid ICF

Answer 4

Plasma - 3L Interstitial fluid - 11L ICF - 28L (1/3 ECF, 2/3 ICF) TBW = 42L

Question 5

Changes in sodium content of ECF lead to what?

Answer 5

Changes in ECF volume –> affects vol of blood perfusing the tissues = effective circulating volume + therefore BP So regulation of Na basically dependent on high and low P baroreceptors

Question 6

What is the renal response to hypovolaemia?

Answer 6

inc. salt and water loss (e.g. diarrhoea, vomiting, xs sweating) –> dec. plasma volume –> dec. venous pressure –> reduced venous return –> decreased atrial pressure –> dec. end diastolic volume –> dec. stroke volume and CO –> reduced BP –> reduced carotid sinus baroreceptor inhibition of sympathetic discharge –> inc. sympathetic discharge –> increased vasoconstriction –> inc. total peripheral resistance –> inc. BP towards normal

Question 7

What does the increased sympathetic discharge caused by hypovolaemia lead to in the kidneys?

Answer 7

Increased renal arteriolar constriction + increase in renin

Question 8

What does an increase in renin lead to?

Answer 8

Increased angiotensin II –> reduced peritubular hydrostatic P (and oncotic pressure increases) so less Na is excreted –> inc. angiotensin II –> inc. aldosterone –> increased DCT Na reabsorption so less Na excreted

Question 9

What type of cells are juxtaglomerular cells?

Answer 9

Specialised smooth muscle cells

Question 10

What hormone do the juxtaglomerular cells release?

Answer 10

Renin

Question 11

When do the juxtaglomerular cells release renin?

Answer 11

1. When BP is low 2. Sympathetic nerve stimulation 3. Macula densa cells send message to JG cells via prostaglandins if low Na concentration in DCT

Question 12

What are the macula densa cells?

Answer 12

Cells in the distal convoluted tubule that sense sodium In low BP, less blood is moving through the nephron so less salt is reabsorbed

Question 13

What is the liver’s role in the RAAS?

Answer 13

Produces angiotensinogen

Question 14

What happens when renin meets angiotensinogen?

Answer 14

Renin cleaves angiotensin to make it angiotensin I

Question 15

What happens to angiotensin I in the RAAS?

Answer 15

Endothelial cells lining BVs (esp in the lungs) produce angiotensin converting enzyme which converts angiotensin I to angiotensin II

Question 16

What are the actions of angiotensin II?

Answer 16

1. Smooth muscle cells in BVs constriction (v. potent vasoconstrictor) 2. Makes kidney cells hold on to more water 3. Pituitary produces ADH –> collecting duct + increases water reabsorption 4. Adrenal gland - produces aldosterone 5. Stimulates thirst mechanism and salt appetite

Question 17

What are the actions of aldosterone?

Answer 17

Increases tubular Na and Cl reabsorption, water retention and K excretion

Question 18

Why is oncotic pressure increased in hypovolaemia and why is this beneficial?

Answer 18

Less water/NaCl in the arterioles therefore oncotic pressure is higher Means we can reabsorb even more of the filtrate at the PCT (75% compared with 70% in normovolaemia)

Question 19

GFR remains largely unaffected until what?

Answer 19

There is a SUBSTANTIAL drop i MBP

Question 20

What is the function of aldosterone?

Answer 20

Regulation of distal tubule Na reabsorption

Question 21

Where are the juxtaglomerular cells located?

Answer 21

They are smooth muscle cells of the afferent arteriole just before it enters the glomerulus

Question 22

With which cells are the JG cells closely associated?

Answer 22

A specialised loop of the distal tubule containing macula densa cells

Question 23

What is the juxtaglomerular apparatus?

Answer 23

Macula densa + JG cells

Question 24

How many peptides make up angiotensin I?

Answer 24

10

Question 25

How many peptides make up angiotensin II?

Answer 25

8

Question 26

When does the liver make angiotensinogen?

Answer 26

Constantly

Question 27

Where does angiotensin II stimulate the production of aldosterone?

Answer 27

In the zona glomerulosa of the adrenal cortex

Question 28

What is the rate limiting step in the RAAS?

Answer 28

Release of renin

Question 29

What things increase renin release?

Answer 29

1. Increased renin release when P in afferent arteriole at level of JG cells is decreased (intrinsic) 2. Increased sympathetic nerve activity –> increased renin release via B1 effect 3. Decreased NaCl delivery at macula densa 4. Angiotensin II feedbacks to inhibit renin 5. ADH inhibits renin release (osmolarity control)

Question 30

What is usually the main determinant of ADH concentration?

Answer 30

Osmolarity (but if sufficient volume change compromises brain perfusion, volume becomes primary drive and body tolerates disturbed osmolarity)

Question 31

What hormone promotes Na excretion?

Answer 31

ANP = atrial natriuretic peptide

Question 32

How do aldosterone and ANP interact?

Answer 32

Aldosterone –> Na reabsorption, K secretion at DCT –> inc. wt due to H2O and Na retention –> volume expansion –> stimulation of ANP from atrial cells –> loss of Na and H2O (natriuresis) BUT aldosterone –> continued K loss because still increases K secretion ANP overrides aldosterone effects on Na reabsorption because of volume expansion (aldosterone escape)

Question 33

Where is ANP secreted? What is it secreted in response to?

Answer 33

Atrial cells Response to expansion of ECF volume

Question 34

What does ANP cause?

Answer 34

Natriuresis (loss of Na and H2O in urine)

Question 35

What happens in uncontrolled DM (where BG is not kept within strict control and exceeds the maximum reabsorptive capacity of the PCT?

Answer 35

Glucose remains in tubule + exerts osmotic effect to retain H2O in tubule Na conc in lumen decreased as larger H2O volume so Na reabsorption decreased and there is a decreased ability to reabsorb glucose as it shares a symport with Na In descending limb of loop of henle there is reduced H2O movement into the interstitium because glucose + Na exert an osmotic effect to retain H2O so fluid in descending limb is not as concentrated Since NaCl pumps in the ascending limbs are gradient limited, medullary interstitial gradient is much less so MUCH less NaCl and H2O is reabsorbed from the loop of henle and interstitial gradient is gradually abolished Macula densa detects high rate of NaCl so renin secretion is suppressed and Na reabsorption at DCT is decreased So basically 6-8L of isotonic urine is produced per day (NB as plasma vol is decreased, stimulation of ADH release via baroreceptors cannot be effective as interstitial gradient has run down) Hypotension can be so severe it can lead to a hyperglycaemic coma due to inadequate BF to the brain

Question 36

What can loop diuretics cause?

Answer 36

K wasting