Glomerular Filtration & Renal Blood flow

Question 1

Basic functional anatomy of filtration apparatus of nephron

Answer 1

• glomerulus = structures involved in filtration
• filtration occurs @ capillary loops ==> Bowman’s capsule of tubule
• arterioles adjacent to capillary bed = act as valves to control blood flow to kidney & regulate GFR

Question 2

Granular cell characteristics

Answer 2

• subset of smooth muscle @ afferent arteriole
• part of juxtaglomerular apparatus
• secrete renin

Question 3

Structural basis of ultrafiltration

Answer 3

1. filtrate passes through gomerular capullary endothelium
   
   1. “fenestrated” epithelium = large holes; plasma passes easily through but RBCs do not
   2. not a major contributor to filtration
2. Basal lamina
   
   1. secreted by both endothelium & epithelium
   2. composed of mucoproteins; negatively charged
   3. contributes to filtration
3. Podocytes = sheet of tubular epithelial cells
   
   1. rounded cells w/”feet” projected towards endothelial layer
   2. “feet” intertwine ==> slit membranes ==> molecular sieve

Question 4

Forces that impact filtration

Answer 4

• pressure differences across filtration membrane
  
  • P_gc = hydrostatic pressure w/in glomerular capillaries (drives filtration)
  • P_t = “backpressure” from narrow Bowman’s capsule (opposes filtration)
• Osmotic forces
  
  • π_gc = “colloid osmotic pressure” = large, unfiltred protein concentration rises w/in glomerular capillaries (opposes filtration)

Question 5

GFR (starling equation) =

Answer 5

• = K (P_gc - P_t - π_gc)
  
  • K = represents constant resistance of membrane to flow

Question 6

Net filtration pressure (NFP) & values =

Answer 6

• = P_gc - P_t - π_gc
• _{=”starling forces”}
• P_gc = 46mmHg
• P_t = 10mmHg
• π_gc = 30mmHg
• NFP = 6mmHg

Question 7

K (in GRF equation) definition

Answer 7

• “total hydraulic conductivity” ==> amount of fluid to flow across glomerulus per unit time per unit pressure
• K = pA
  
  • p=specific hydraulic conductivity
  • A=total surface area of glomeruli w/in kidneys
  • A = ~1 m²

Question 8

GFR regulation and homeostasis

Answer 8

• relatively constant in healthy ppl
• filtration process = nonspecific ==> changes in GFR generally not a good mechanism for maintaining ECF conditions
• changes in p (specific conductivity) ==> changes in GFR

Question 9

Regulation of Pgc

Answer 9

• P_gc = ~1/2*MAP
• regulation is important b/c if P_gc changed in proportion to MAP ==> overwhelm kidneys/filtration might go to zero
• P_gc regulated via autoregulation

Question 10

Characteristics of autoregulation

Answer 10

• helps maintain GFR constancy
• occurs via myogenic mechanism ==> MAP changes ==> smooth muscles cells w/in arteriole constrict/dilate to keep the downstream capillarly blood flow constant
• afferent arteriole = regulating valve ==> maintains P_gc constant ==> GFR remains constant
• works best between 75-150mmHG (MAP), but some residual error as MAP increases

Question 11

GFR changes in (severe, chronic) hypovolemia

Answer 11

• hypovolemia ==> increased peripheral resistance ==> shunting to vital organs
• kidneys aim to preserve GFR while decreasing RBF
• GFR maintained via coordinate constriction of afferent and efferent arterioles
  
  • afferent constriction ==> decreased RBF, but decreases P_gc
  • efferent constriction ==> flow diverter ==> restores P_gc & further decreases RBF (via increased resistance)

Question 12

Stimulation of glomerular hypovolemic response

Answer 12

• long-lasting decline in MAP ==> baroreceptor reflex ==> increase in renal sympathetic nerve activity ==> synapses @ afferent and efferent arterioles ==> arteriole muscle contraction
• stimulation of afferent arteriole ==> renin release
• intrarenal baroreceptors on granular cells detect reduced pressure ==> increase renin

Question 13

Filtration equilibrium definition

Answer 13

• NFP reaches 0 at some point before plasma exits glomerular capillary
• ==> “double hit” of decreased NFP (due to hypovolemia) + decreased effective area for filtration

Question 14

Role of renal prostaglandins in hypovolemic response

Answer 14

• renal prostaglandins produced by renal interstitial cells @ kindey medulla between renal pyramids
• secreted in response to AgII ==> local dilatory effect @ renal arterioles
• help maintain adequate RBF by blunting AgII <== prevent ischemic injury to renal tubular cells
• selective for afferent arteriole ==> tends to restore GFR