PHYS - Renal Blood Flow

Question 1

WATER PERMEABILITY OF THE NEPHRON

Answer 1

• Path of fluid through nephron: afferent arteriole → glomerulus (filter) → efferent arteriole → proximal tubule → loop of Henle → distal tubule → collecting duct
• Water permeability based on protein composition of the tight junctions between epithelial cell lining and decreases through the nephron to the collecting duct
  
  • Water can pass between cells
  • Disease, injury, or mutation to these proteins → serious disruption of normal renal function
  • Increased tightness of junctions = increased resistance to water permeability
    
    • Glomerulus is considered 0 resistance
    • Collecting duct = 1000x resistance (no water permeability through TJs)
• Collecting duct water permeability through aquaporins (AQP) in the cell
  
  • Water passes into the cell from the lumen and then out through an AQP on the blood vessel side
  • Luminal AQP2 is regulated by ADH/AVP
    
    • Antidiuretic hormone or arginine vasopressin
    • Opens the pores to water flow
  • Blood AQP’s not regulated

Question 2

NEPHRON STRUCTURE

Answer 2

• Cortical nephrons
  
  • 85% of all nephrons
  • Shorter loop of Henle
  • Renal artery → afferent arteriole → glomerulus → efferent arteriole → peritubular capillary bed around loop of Henle → venules → renal vein
• Juxtamedullary nephron
  
  • 15% of all nephrons, filters 90% of the blood
  • Long loop of Henle, responsible for creating the interstitial osmotic gradient
  • Renale artery → afferent arteriole → glomerulus → efferent arteriole → vasa recta → peritubular capillaries → vasa recta → renal vein
  • Vasa recta are 2 sets of parallel blood vessels that run along the loop of Henle
• Renal circulation
  
  • Resistance increases in series through renal circulation through the arterioles
  • No resistance associated with veins/venules
  • Increased resistance = decreased flow = increased glomerular pressure= increased filtration
• Juxtamedullary apparatus
  
  • Juxtaglomerular cells on arterioles near glomerulus (mostly afferent arteriole) secret renin in response to low blood flow
  • Macula densa cells alone the distal tubule are specialized cells that sense flow based on concentration of NaCl
  • Mesangial cells surround the glomerulus/arterioles are participate in signaling blood flow changes

Question 3

TUBULOGLOMERULAR FEEDBACK (TGF)

Answer 3

• TGF is the mechanism by which GFR (glomerular filtration rate) is kept constant despite changes in arterial pressure based on NaCl concentration in distal tubule
• Low arterial pressure
  
  • Decreased GFR
    
    • Slow filtration rate = increase NaCl filtration/loss
      
      • Macula densa cells in distal tubule detect low NaCl through Na+/K+ ATPase transporters
        
        • Stimulate renin release from JG cells → angiotensin II → efferent arteriole contraction → increased R_e
        • Causes relaxation of afferent arteriole → decreased R_a
          
          • Increased GFR
• High arterial pressure = increased GFR
  
  • Macula densa = increase NaCl uptake
    
    • Increased ATP use → increased adenosine
      
      • Binds to adenosine receptor → Ca2+ release
        
        • Stimulate SM contraction and inhibits JG cell renin release
          
          • Increased R_a
          • Decreased R_e
• Pressure decreases through renal circulation from renal artery to renal vein, but is maintain at constant P in glomerulus and peritubular capillary beds to maintain constant filtration

Question 4

RENAL BLOOD FLOW

Answer 4

• RBF = ΔP/(R_a + R_e)
  
  • Decreased R_a = Increased RBF through afferent = Increased P_G = INCREASED GFR
  • Decreased R_e = Increased RBF through efferent = Decreased P_G = decreased GFR
• Filtration Fraction = GFR/Renal Plasma Flow
  
  • Normal is about 20%
  • Can be modified by stimulating SM of efferent arteriole
  • Increased R_e (vasoconstriction) = increased FF
  • Decreased R_e (vasodilation) = decreased FF
• Renal blood flow is maintained through
  
  • Autoregulation
    
    • Myogenic response
      
      • Increased perfusion pressure = increased wall tension = R_a SM contraction = decreased RBF = decreased P_G
    • TGF (tubuloglomerular feedback)
  • Hormones – Renin-Angiotensin-Aldosterone System (RAAS)
    
    • Renin release stimulated by low BP/volume leading to:
      
      • Decreased stretch on afferent arteriole
      • Decreased NaCl delivery to macula densa
      • Increased sympathetic nerve activity (decreased BP, decreased baroreceptor activity)
    • Renin converts angiotensinogen → angiotensin I
      
      • ACE → angiotensin II
        
        • Vasoconstriction of efferent arterioles
        • Thirst
        • ADH release from brain (water retention)
        • Stimulate sympathetic nerves → NE
        • Stimulate adrenal gland → aldosterone (Na retention)
  • Sympathetic Nervous System

Question 5

ACUTE RENAL FAILURE

Answer 5

• dysregulation of extracellular fluid volume (EFV) and electrolytes
• Prostaglandins – mainly cause vasodilation (but some types vasoconstrict)
  
  • Decreased EFV
    
    • Real: hemorrhage or dehydration
    • Perceived: CHF → volume in venous circulation → baroreceptors located in arteries sense low pressure
      
      • Baroreceptors → renin secretion & sympathetic stimulation
        
        • Angiotensin II → contract renal arterioles
        • Prostaglandin synthesis → vasodilation
        • Homeostatic balance between dilation and contraction (but more contraction)
          
          • Decreased RBF (increased NaCl reabsorption)
  • NSAIDs inhibit prostaglandins, shifting the balance toward complete vasoconstriction, extremely decreased RBF → acute renal failure
• ACE inhibitors – ex: Lisinopril, for HT
  
  • RAS (renal artery stenosis)
    
    • Decreased P_a = decreased stretch on JG cells
      
      • Renin secretion –ACE→ angiotensin II and aldosterone
        
        • Ang II increases R_e → increased P_G → increased GFR
        • Aldosterone → secondary HT
          
          • Caused by increased aldosterone from feedback mechanisms
          • Primary HT is increased aldosterone production from an adrenal gland tumor (for example)
  • ACE inhibitors prevent angiotensin II production → RAS → decreased P → extremely low GFR, acute renal failure

Question 6

RENAL OXYGEN CONSUMPTION

Answer 6

• Generally, increased tissue work = increased O2 consumption = increased blood Q
• In the kidneys, the blood filters, increased blood Q = increased work by Na+/K+ ATPase = increased O2 consumption
• Renal O2 consumption is directly proportional to GFR and Na+ reabsorption
  
  • Increase GFR = increase renal O2 consumption
  • Increase GFR = increase renal O2 consumption