regulation of homeostasis by the kidney- fluid balance

Question 1

describe ADH? 7

Answer 1

• The collecting duct is relatively impermeable to the movement of the water and solutes, but the permeability of the collecting duct can be increased by the action of ADH
• It is the most important hormone that regulates water balance
• A nonapeptide with Mw of just over 1000
• Also known as vasopressin or 8-arginine-vasopressin (AVP)
• Plasma half-life is 10-15 min
• ADH acts on V2 receptors on the basal membrane of principal cells in the collecting duct
• This leads to insertion of aquaporin-2 (AP-2) water channels into the apical surface

Question 2

what are the actions of ADH? 3

Answer 2

• Interacts with V2 receptors on basolateral surface of principal cells in collecting duct of tubule
• Results in increased permeability of collecting duct to H2O by insertion of aquaporin-2 water channels on the apical surface
• Maximal ADH leads to the production of low amounts of concentrated urine

Question 3

describe volume regulation by ADH? 5

Answer 3

• ADH released in response to changes in plasma osmolality and effective circulating volume
• These changes are detected by osmoreceptors and baroreceptors
• Consider dehydration: increased plasma osmolality stimulate osmoreceptors in the hypothalamus which trigger ADH release
• This results in more water reabsorbed from collecting ducts in the kidney back into the circulation- leading to increased effective circulating volume
• Increased osmolality also stimulates a second group of osmoreceptors in the hypothalamus which trigger thirst- promotes water intake which enter the circulation- increasing effective circulating volume

Question 4

describe counter current multiplication? 6

Answer 4

• Urea plays a part
• Active transport of NaCl contributes 600-1000mOsm, the remainder is due to urea
• Urea is freely filtered at the glomerulus
• Some reabsorption in the proximal tubule, but LOH and distal tubule re relatively impermeable to urea
• Urea can diffuse out of the collecting duct into the medulla down its concentration gradient
• This adds to the osmolality of the medullary interstitium

Question 5

what do baroreceptors do? 10

Answer 5

• detect changes in ECV
• Central vascular sensors:
• Low pressure blood volume receptors:
• Large systemic veins
• Cardiac atria
• Pulmonary vasculature
• High pressure arterial stretch receptors:
  carotid sinus
• Aortic arch
• Renal afferent arteriole
• .
• Sensors in the CNS and liver

Question 6

describe the control of the effective circulating volume ? 7

Answer 6

• Feedback control of ECV exists and is mediated by baroreceptor stimulation
• Changes in ECV trigger 4 parallel effector pathways which act on the kidney:
• RAAS
  sympathetic nervous system
• ADH release
• ANP release
• Together these change a renal haemodynamic and Na+ transport by renal tubule cells
• ECV regulation= Na+ regulation

Question 7

describe RAAS and regulation of homeostasis by the kidney? 4

Answer 7

• Principal factor controlling plasma AngII levels is renin release from the JGA
• Decreased ECV stimulates renin release- decreased renal perfusion pressure detected in the afferent arteriole- the renal baroreceptor
• Decreased concentration in the distal tubule detected by the macula densa cells- the renal Na+ sensor
• Decreased systemic BP also triggers effects of the sympathetic nervous system supplying the JGA

Question 8

what are the important actions of AngII? 6

Answer 8

• All the actions of AngII are designed to increase ECV
• Enhances tubular Na+ transport in the kidney which promotes Na+ and water reabsorption from the tubule
• Stimulation of aldosterone release from the adrenal cortex so more Na+ and water is reabsorbed from the distal tubule/collecting duct
• Acts on the hypothalamus to stimulate thirst and ADH release into the circulation- water intake adds to the ECV, ADH increases water reabsorption from the collecting duct
• Vasoconstriction of renal and other systemic vessels so systemic BP increases
• Renal cell hypertrophy longer term- so more protein synthesis of Na+ transporters and channels

Question 9

what are the important actions of aldosterone? 2

Answer 9

• All the actions of aldosterone are designed to increase ECV and by lowering plasma K+ concentrations
• Important in conserving Na+ and water, but also important in preventing large variation in plasma K+ levels (by causing its excretion out of the kidney)

Question 10

describe atrial netiuretic peptide (ANP)? 7

Answer 10

• In contrast the actions of ANP are all designed to lower ECV:
• Atrial myocytes synthesize and store ANP
• Increase ECV causes atrial stretch which leads to ANP release into circulation
• ANP promotes natriuresis (increased Na+ excretion from the kidney)
• Also causes renal vasodilation so increases blood flow- increase in GFR so more Na+ excreted
• More Na+ reaches the macula densa so renin release by JGA is reduced- reduces the effects of AngII
• Overall effect= inhibits actions of renin and opposes effects of AngII