Renal Physiology

Renal Physiology

note:  click here for nephron map -  very useful for all renal lectures

renal blood flow = 20% of cardiac output

• renal artery → interlobar a → afferent arteriole →efferent arteriole
• Pcap ≈ 40 mm Hg  - higher than most systemic capillaries
• Capillaries are fenestrated = high Kf
• gomerular = filtration
• peritubular = reabsorption
• subset = vasa recta -  surround loop of Henle in juxta medullary nephrons - get 10% of total blood flow
• juxtagomerular cells = afferent arterioles
• produce renin

regulation of renal blood flow

• Intrarenal (Autoregulation)
• Myogenic tone
• maintains Pcap and GFR
• Tubuloglomerular feedback
• macula densa cells sense content of ascending tubule
• e.g., inc. in Na delivery = high GFR = constricts afferent arteriole = dec. Pcap = dec. GFR
• volume contraction increases sensitivity of tubular glomerular feedback
• mediators
• adenosine constricts afferent arterioles
• • PGE2
  • Thromboxane
  • HETE
  • Angiotensin II
• volume expansion opposite
• mediators
• ANP
• – NO
• – cAMP
• – PGI2    
• – High-protein diet
• Extrarenal (Extrinsic regulation)
• – Sympathetic nerves– 
• 
  
• Kidneys
•  Constricts afferent and efferent arterioles to decrease 
• renal blood flow
•  Potently increases Na+ reabsorption in proximal tubule
•  Large activation decreases GFR
• Vascular smooth muscle
•  Constricts arteries to decrease renal blood flow
• Endocrine
•  Stimulates renin secretion (-receptors)
•  RAAS
• Angiotensin 2
• Kidneys
•  Constricts afferent and efferent arterioles 
•  Promotes Na and H2O reabsorption 
•  Increases sodium reabsorption in proximal tubule
• Vascular smooth muscle
•  Constricts arteries
• Peripheral and Central Nervous Systems
•  Increases NE release (central and peripheral)
• Brain
•  AT1
• receptors in the hypothalamus stimulate thirst
•  Stimulates ADH secretion.
• Adrenal cortex
•  Stimulates zona glomerulosa cells to secrete aldosterone.

Aldosterone Effects

• Increased distal tubule
  

  Na+ permeability
• – ENaC inserted into luminal
  

  membrane
• – Decreased ENac degradation
  

  (Sgk1)
• – Increased Na/K-ATPase
  

  activity
• • Increased K+ and H+
  

  secretion
• – Increased Na/K-ATPase
  

  activity
• – Increased K permeability.

ADH effects

• • Stimulates water reabsorption in
  

  the collecting duct 
• – Aquaporin inserted into luminal
  

  membrane
• – Increased Na reabsorption in
  

  ascending limb
• • Increased urea reabsorption in
  

  the medullary collecting duct
• – Insertion of urea transporters into
  

  luminal membrane
• – Elevates soute concentration of
  

  the interstitium
• • Vasoconstriction
• – Elevates arterial pressure

Atrial Natriuretic Peptide  =  opposite effects of RAAS

• • Regulation of ANP/BNP secretion
• – Stretch of the atria stimulates ANP secretion 
• – Stretch of the ventricle stimulates BNP secretion
• • Mechanism of NP actions
• – Activate NPR and guanylyl cyclase causing vasodilation.
• – Afferent arteriole dilates more than efferent increasing GFR.
• – Decreases Na+ reabsorption in medullary collecting duct through activation of amiloride-sensitive Na+ channels to promote natriuresis and diuresis. 
• – Inhibits secretion of aldosterone and renin.

Prostaglandins - PGI2, PGE2 - induce afferent dilation  (help maintain GFR during fight or flight