LO - Renal

Question 1

Tubuloglomerular feedback mechanism

Answer 1

A special mechanism which links [NaCl] at macula densa cells with renal arterial resistance and GFR. Ensures constant delivery of Na to distal tubules.
2 components: afferent and efferent mechanism.

Macula densa cells detect a decrease in [NaCl] and generate a signal with two effects:

1. Reduces afferent arteriole resistance to blood flow > increases glomerular hydrostatic pressure > GFR returns to normal.
2. Stimulates release of renin from juxtaglomerular cells of afferent and efferent arterioles > activates renin-angiotensin mechanism which causes vasoconstriction of efferent arteriole > increases glomerular hydrostatic pressure > GFR returns to normal.

Question 2

Aldosterone - effect on tubular reabsorption/mechanism

Answer 2

Increases Na+ reabsorption and K+ and H+ secretion.
Mechanism is by stimulating the Na+/K+ ATPase pump on the basolateral side of the collecting duct membrane and increasing Na permeability on the luminal side.

Most important stimuli for aldosterone release is extracellular [K+] and angiotensin II levels.

Question 3

Angiotensin II - effect on tubular reabsorption/mechanism

Answer 3

Body’s most powerful Na-retaining hormone.

Angiotensin II increases Na/water reabsorption by renal tubules through 3 main mechanisms:

1. Stimulates release of aldosterone, which increases Na reabsorption.
2. Constricts the efferent arterioles:
   - reduces peritubular capillary hydrostatic pressure > increases reabsorption in proximal tubule

• raises filtration fraction in glomerulus > increases protein concentration in peritubular capillaries > increases reabsorptive force in peritubular capillaries and therefore tubular reabsorption
  3. Directly stimulates Na reabsorption by stimulating Na/K ATPase pump , Na/H exchange and N/HCO3- co-transport.

Question 4

ADH - effect on tubular reabsorption/mechanism

Answer 4

Increases water permeability in distal tubule and collecting duct.

Binds to V2 receptor in late distal tubules and collecting ducts. V2 is a GPCR so causes the formation of cAMP second messenger which initiates the phosphorylation cascade that causes AQP-2 to insert on the luminal side of tubular membranes.

Question 5

Formation of dilute urine:

Answer 5

Continued electrolyte reabsorption, decreased water reabsorption.

Mechanism: Decreased ADH release, reduced water permeability.

Question 6

Formation of concentrated urine:

Answer 6

Continued electrolyte reabsorption, increased water reabsorption.

Mechanism: Increased ADH release, increased water permeability.

Question 7

Main systems involved in maintaining extracellular fluid osmolarity and sodium concentration:

Answer 7

1. Osmoreceptor-ADH system

2. Thirst Mechanism

Question 8

Thirst Mechanism:

Answer 8

Increase Thirst:
Increased plasma osmolarity, angiotensin II levels
Decreased blood volume, pressure
dry mouth

Decrease Thirst:
Decreased plasma osmolarity, angiotensin II levels
Increased blood volume, pressure
gastric distension

Question 9

Osmoreceptor-ADH system

Answer 9

INCREASED fluid osmolarity causes osmoreceptors in the anterior hypothalamus to shrink and fire.

This signal is sent to the supraoptic nuclei in the hypothalamus causing release of ADH from secretory granules in axons located in posterior pituitary.

ADH increases water permeability in late distal tubules and collecting duct, increased water reabsorption, dilution of extracellular fluid which corrects osmolarity.