Lecture 7 - ECF Volume Regulation 1 and 2 Flashcards
What ions are the major ECF osmoles?
Na Cl
What substance is the major ICF osmole?
K salts
How is regulation of ECF volume carried out?
By regulating body Na
Describe the total distribution of body water between: Plasma Interstitial fluid ICF
Plasma - 3L Interstitial fluid - 11L ICF - 28L (1/3 ECF, 2/3 ICF) TBW = 42L
Changes in sodium content of ECF lead to what?
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
What is the renal response to hypovolaemia?
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
What does the increased sympathetic discharge caused by hypovolaemia lead to in the kidneys?
Increased renal arteriolar constriction + increase in renin
What does an increase in renin lead to?
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
What type of cells are juxtaglomerular cells?
Specialised smooth muscle cells
What hormone do the juxtaglomerular cells release?
Renin
When do the juxtaglomerular cells release renin?
- 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
What are the macula densa cells?
Cells in the distal convoluted tubule that sense sodium In low BP, less blood is moving through the nephron so less salt is reabsorbed
What is the liver’s role in the RAAS?
Produces angiotensinogen
What happens when renin meets angiotensinogen?
Renin cleaves angiotensin to make it angiotensin I
What happens to angiotensin I in the RAAS?
Endothelial cells lining BVs (esp in the lungs) produce angiotensin converting enzyme which converts angiotensin I to angiotensin II
What are the actions of angiotensin II?
- 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
What are the actions of aldosterone?
Increases tubular Na and Cl reabsorption, water retention and K excretion
Why is oncotic pressure increased in hypovolaemia and why is this beneficial?
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)
GFR remains largely unaffected until what?
There is a SUBSTANTIAL drop i MBP
What is the function of aldosterone?
Regulation of distal tubule Na reabsorption
Where are the juxtaglomerular cells located?
They are smooth muscle cells of the afferent arteriole just before it enters the glomerulus
With which cells are the JG cells closely associated?
A specialised loop of the distal tubule containing macula densa cells
What is the juxtaglomerular apparatus?
Macula densa + JG cells
How many peptides make up angiotensin I?
10
How many peptides make up angiotensin II?
8
When does the liver make angiotensinogen?
Constantly
Where does angiotensin II stimulate the production of aldosterone?
In the zona glomerulosa of the adrenal cortex
What is the rate limiting step in the RAAS?
Release of renin
What things increase renin release?
- 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)
What is usually the main determinant of ADH concentration?
Osmolarity (but if sufficient volume change compromises brain perfusion, volume becomes primary drive and body tolerates disturbed osmolarity)
What hormone promotes Na excretion?
ANP = atrial natriuretic peptide
How do aldosterone and ANP interact?
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)
Where is ANP secreted? What is it secreted in response to?
Atrial cells Response to expansion of ECF volume
What does ANP cause?
Natriuresis (loss of Na and H2O in urine)
What happens in uncontrolled DM (where BG is not kept within strict control and exceeds the maximum reabsorptive capacity of the PCT?
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
What can loop diuretics cause?
K wasting
