Control Of GFR And Renal Blood Flow

Question 1

Factors that affect GFR via Starling forces

Answer 1

. Change in Kf: lower Kf dec. GFR
. Change in capillary oncotic pressure: lower oncotic pressure inc. GFR
. Change in Bowman’s space hydrostatic pressure (obstruction of urinary tract): inc. hydrostatic pressure dec. GFR

Question 2

Regulation of GFR

Answer 2

. Regulated by changing capillary hydrostatic pressure
. Changes in Pgc mediated y changes in glomerular arteriole resistance
. Afferent constriction dec. Pgc, dec. GFR and dec. RBF
. Efferent constriction inc. Pgc, inc. GFR, and dec. RBF
. Efferent dilation: dec. Pgc, dec. GFR, inc. RBF
. Afferent dilation: inc. Pgc, inc. GFR, inc. RBF

Question 3

What happens in arterioles when hemorrhage occurs?

Answer 3

. Loss of blood volume causes compensatory inc. in SNS
. Constrict afferent and efferent arterioles (dec. RBF and GFR)
. Dec. in filtered load of Na and H2O
. Dec. Na and H2O excretion

Question 4

Regulation of RBF and GFR by nerves and hormones

Answer 4

. Sympathetic nn.: innervate both arterioles and tonically active at low level, strong activation (from fall in BP, fear, pain o exercise) of renal nn. Dec. RBF and GFR
. AII: binds o AT1 and AT2 receptors (AT1 predominate for hemodynamics), AI conveyed to AII by ACE that then releases aldosterone, renin produced and stored by special smooth mm. Cells in afferent and efferent arterioles

Question 5

How renin release is stimulated

Answer 5

. Dec. in ECF or BP
. This dec. GFR and macula densa senses dec. NaCl which stimulates release
. Dec. in renal perfusion pressure sensed in afferent arterioles stimulates release
. Activation of SNS via beta-1 receptor stimulates release (NE and E are NTs)

Question 6

How AII supports GFR when RPF dec.

Answer 6

. Preferentially raising efferent arteriolar resistance, physiologic levels of AII prevent excessive dec. in Pgc and GFR under conditions of volume contraction or dec. BP
. AII binds to afferent and efferent arterioles but efferent arterioles are more sensitive
. AII also stimulates Na and H2O reabsorption in prox. Tubule

Question 7

Renal hemodynamic effects of NO

Answer 7

. Vasodilatory role under basal conditions
. Counteracts vasoconstriction produced by AII and catecholamines
. Keeps RBF from going too low
. Release stimulated by shear stress acting on endothelial cells (inc. when vessel diameter dec.)
. Also released by ACh, bradykinin, ATP, and histamine

Question 8

. GFR in diabetic nephrology

Answer 8

. GFR pressure drives albuminuria, podocyte loss, and glomerulosclerosis
. Inc. in GFR causes afferent arteriolar dilation and NO can cause excessive dilation
. Over years high pressure promotes glomerular damage and contributes o dec. in renal function assoc. w/ DM

Question 9

Role of AII blockade to reduce glomerular hypertension

Answer 9

. Lowering AII action on arterioles via ACE inhibitors or AT1 receptor blockers will preferentially dec. efferent arteriolar resistance and dec. Pgc

Question 10

Mechanism of how lowering AII levels slows progression of diabetic renal disease

Answer 10

. Reduce efferent arteriolar constriction lowering glomerular hydrostatic pressure
. Lower systemic bp
. Reduce proteinuria
. Reduce production of cytokines that initiate mesangial and tubular scarring

Question 11

Renal hemodynamic effects of prostaglandin (PG)

Answer 11

. Derived from lipid (arachidonic acid) in cell membrane
. PFE2 and prostacyclin (PGI2): vasodilatory, stimulated by dec. ECF volume, inc, AII, SNS, and stress to counteract vasoconstrictor effects and prevent ischemia
. Thromboxane A2 and PGF 2 alpha are vasoconstrictors

Question 12

Prostaglandins in pathophysiologic conditions

Answer 12

. Patient already compromised RBF, GFR, high degree vasoconstrictor production
. Inhibition of vasodilatory PG production w/ NSAIDS can precipitate rapid dec. in GFR due to unopposed vasoconstriction bc vasodilatory PGs preferentially working at afferent arterioles

Question 13

Bradykinin

Answer 13

Vasodilator
. Stimulates release of NO and PG from endothelial cells
. Inc. GFR and RBF
. ACE breaks down bradykinin

Question 14

Autoregulation of GFR and RBF

Answer 14

. Avoids wide swings in fluid and solute excretion caused by arterial pressure fluctuations
. GFR and RBF remain relatively constant over an arterial pressure range of 90-180 mmHg
. Below 90 mmHg, RBF, and GFR will follow arterial pressure
. Can dampen the influence of hormones and sympathetic activity on RBF and GFR

Question 15

Myogenic mechanism

Answer 15

. Stimulus: change in renal arterial pressure in afferent arteriole
. Vascular smooth mm. Contracts when stretched and relaxes when less stretched so flow is maintained constant by changing arteriolar resistance

Question 16

Tubuloglomerular feedback mechanism

Answer 16

. Modifies GFR to keep the amount of Na delivered to the distal tubule and collecting duct relatively constant
. Avoids excessive losses of Na and H2O assoc. w/ inc. in GFR
. Stimulus: tubular flow-dependent changes in luminal NaCl presented to macula densa
. Sensor: macula densa

Question 17

Effect of tubuloglomerular feedback mechanism when GFR is elevated

Answer 17

. When GFR is elevated and tubular NaCl conc. Inc., the macula densa releases ATP and adenosine
. Compounds interact w/ their receptors (P@x and A1) on afferent renal arteriolar cells and stimulate inc. in intracellular Ca
. Results in contraction of the afferent arteriolar smooth muscle
. Inc. in resistance brings GFR back to normal by dec. glomerular capillary pressure
. Inc. in intracellular Ca inhibits release of renin from afferent arteriole

Question 18

Effect of tubuloglomerular feedback mechanism when GFR is low

Answer 18

. Tubular NaCl dec.
. Macula densa responds by dec. the release of ATP and adenosine
. Vascular smooth mm. Intracellular Ca dec. and the afferent arteriole dilates (inc. glomerular capillary pressure) to bring GFR back to normal
. Dec. in intracellular Ca stimulates renin release

Question 19

tubuloglomerular feedback and renal hemodynamic response to an acute protein load

Answer 19

. Acute inc. in filtered load of AAs (normal GFR, inc. plasma AA conc.)
. Reabsorption of large load of AAs in prox. Tubule is accompanied by Na
. Luminal NaCl conc. Is lower than usual (for level of GFR) at macula densa
. Macula densa signals the afferent arteriole to dilate (thinking GFR is too low)
. RBF and glomerular capillary pressure inc. which inc. GFR
. This is the reason why people w/ kidney disease are placed on low protein diet

Question 20

Glomerular filtration preszsure that drives albuminuria, podocyte loss, and glomerulosclerosis in DM

Answer 20

. DM initiates Na-glucose cotransporter 2 (SGLT2) that compromises TGF by lowering Na (signal sent to macula densa)
. Process directly dilates afferent arteriole and indirectly induces vasoconstriction of efferent arteriole
. Results in inc. in filtration pressure and GFR
. RAAS inhibition corrects inc. glomerular afterload but not dilation of afferent arteriole
. Issue only corrected though SGLT2 inhibition that restores TGF and reverses low Na delivery to macula densa
. Restores TGF-initiated vasoconstriction of AA