1 - Hormonal Regulation of Kidney Function

Question 1

Objective: Site of Production, Control of Secretion, Actions

Renin

Answer 1

• Production: Granular Cells of JGA
• Control of Secretion:
  
  • (+) Decreased Blood Pressure - Intrarenal baroreceptor
  • (+) Decreased delivery of NaCl and tubular fluid volume to macula densa
  • (+) Sypathetic Nervous System causes both of these
  • (-) Angiotensin II exerts negative feedback
• Actions: Converts Angiotensinogen to Angiotensin I

Question 2

Objective: Site of Production, Control of Secretion, Actions

Angiotensin II

Answer 2

• Production: Systemic Circulation; can be produced intrarenally
  
  • ​40% A1->A2 occurs in lung
• Control of Secretion: Concentration directly related to [Renin] in circulation
• Actions: Renal Na+/Water retention (raise BP)
  
  • Direct: Stimulates Na+ reabsorption in PT
  • Indirect: Aldosterone Secretion (adrenal cortex)
  • Indirect: ADH Secretion, increase thirst
  • Promotes vasoconstriction

Question 3

Objective: Site of Production, Control of Secretion, Actions

Prostaglandins

Answer 3

• Location: Kidney
  
  • Glomerular and Vascular Endothelium
  • Medullary/Cortical Collecting Tubule cells (main site)
  • Renomedullary Cells
• Production: Derived from arachinonic acid
  
  • Increased by Vasoconstrictors (ANG II, Norepinephrine, ADH
• Action: Local intrarenal vasodilation
  
  • ​Counter renal vasoconstriction; minimizes renal ischemia

Question 4

Objective: Site of Production, Actions

Bradykinin

Answer 4

• Production: Kidney cells and plasma kallikrein
• Action: Vasodilation
  
  • ​Counteracts renal vasoconstriction
  • Natriuresis and Diuresis

Question 5

Objective: Site of Production, Control of Secretion, Actions

ADH (Antidiuretic Hormone)

Answer 5

• Location:
  
  • Formed in supraoptic/paraventricular nuclei of the hypothalamus
  • Stored in Post. Pit. for release
  • Collecting Tubule fast response
• Release Control:
  
  • Increased Hyperosmolality
  • Low blood volume
• Actions:
  
  • (+) V₂ receptors in Principal Cells - Increase water reabsorption
    
    • ​Increase in luminal water channels
  • (+) V₁ receptors on renal / systemic vasculature; vasoconstriction (vasopressin)
• Inhibited by:
  
  • Prostaglandins

Question 6

Objective: Location, Release, Actions

Aldosterone

Answer 6

• Location: Zona Glomerulosa of Adrenal Cortex
  
  • Cortical / Medullary Collecting Duct Principal Cells
    
    • Na / K Channels
    • Na-K-ATPase Enzymes
  • Intercalated Cells
    
    • H+ secretion
• Release:
  
  • (+) Increased Angiotensin II
  • (+) Increased [K⁺]_Plasma
    
    • _​Very sensitive
• Actions:
  
  • Increased Na / Cl reabsorption
  • Increased K+ / H+ secretion
    *

Question 7

Objective: Site of Production, Control of Secretion, Actions

ANP

Answer 7

• Location: Granules in atrial myocytes, right atrium
• Release: High Volume, effects counter!
  
  • (+) Increased Atrial Stretch in Hyperbolemic States
    
    • Proximule Tubule enzymes rapidly degrade
• Actions:
  
  • Vascular Dilation
  • Diuresis / Natriuresis
    
    • Renal:
      
      • Inhibits Na reabsorption
      • Inhibits ADH water reabsorption
      • Hyperfiltration (↑GFR)
      • Inhibits Renin release
    • Extrarenal:
      
      • Inhibits aldosterone biosynthesis
      • Inhibits ADH secretion

Question 8

Objective: Site of Production, Control of Secretion, Actions

Vitamin D

Answer 8

• Production:
  
  • Formed by UV-radiation in skin, food
  • Hydroxylated in liver, again in kidney to form active compound (1,25 Dihydroxyvitamin D₃)
• Control:
  
  • (+) PTH - Fall in plasma [Ca²⁺]
  • Hypophosphatemia (low plasma phosphate)
• Actions:
  
  • Increase intestinal absorption of calcium/phosphate
  • Decrease release of PTH
  • Increase bone resorption
  • Increase kidney calcium reabsorption

Question 9

Objective: Site of Production, Control of Secretion, Actions

PTH

Answer 9

• Location: Parathyroid Glands
• Release:
  
  • (+) Low Plasma [Ca²⁺]
• Actions: Increase plasma calcium
  
  • Bone Resorption
  • Renal:
    
    • Promotes Vitamin D formation
    • Increases Ca²⁺ reabsorption
    • Increase phosphate excretion

Question 10

Objective: Site of Production, Control of Secretion, Actions

Erythropoietin

Answer 10

• Location: Peritubular capillary endothelial cells
• Release: Decreased oxygen delivery to kidney (anemia, hypoxemia, decreased RBF)
• Action: Acts on erythroid precursor cells in bone marrow to increased erythropoiesis

Question 11

Explain the Renin-Angiotensin-Aldosterone System

Answer 11

Low Blood Pressure Stimulates Kidney

↓

Kidney Releases Renin (enzyme)

↓

Angiotensinogen → Angiotensin I

↓

Angiotensin I → Angiotensin II (req’s ACE)

↓ ↓(+)

↓ Aldosterone

↓ ↓

CV Constriction Salt/H20 Retention (kidney)

↓

Increase Blood Pressure

Question 12

Syndrome of Inappropriate ADH Secretion (SIADH)

Answer 12

Surgical patients have a persistent rise in ADH due to stress/pain

Result in water retention with hyponatremia if free water (solute free) is administered post-op

Question 13

Diabetes Insipidus

Central vs Nephrogenic

Answer 13

• Disorder characterized by intense thirst, and excretion of large amounts of diluted urine (polyuria)
• Central Diabetes Insipidus: Decreased ADH secretion
  
  • ​Head trauma, brain infections; req’s ADH
• Nephrogenic Diabetes Insipidus: Decreased ability to concentrate urine due to resistance to ADH in the kidney
  
  • Systemic or inherited disorders; decrease AQP2 in collecting duct

Question 14

Explain the concept of aldosterone escape

Answer 14

• Prolonged treatment with aldosterone results in brief period of salt retention
• Effect on K+ excretion is sustained
• Escape due to rise in EC volume which decreases Na reabsorption in proximal tube