Endo – Renal/Adrenal

Master answer

Non-RAAS Endocrine Functions

Vitamin D

Vitamin D has a complex metabolic pathway which meanders through a number of organ systems:

• Vitamin D2 (ergocalciferol) only in diet
• Vitamin D₃ (cholecalciferol) absorbed in diet or produced in skin by the action of UV light
  • 7-dehydrocholesterol à 7-dehydroxycholecalciferol à cholecalciferol
• Liver: Cholecalciferol hydrolysed à 25-hydroxycholecalciferol (25-OHD₃)
  • Enzyme: Vitamin D25-hydroxylase (CYP450 enzyme)
• Released into plasma, binds to Vitamin D-binding protein (a globulin carrier protein)
• Kidney: 25-OHD₃ hydrolysed à 1,25-dihydroxycholecalciferol (calcitriol – active form)
  • in the proximal tubule, Enzyme: 1alpha hydroxylase
  • Released into circulation
  • Transported by Vitamin D binding enzyme to intestine, kidney, bone

Erythropoietin

Secretion of EPO to stimulate RBC production.
Erythropoiesis is stimulated by EPO release:

• In adults, EPO is released from the:
  • Peritubular capillary fibroblasts (85%)
  • Liver (15%)
• EPO is released in response to:
  • Hypoxia (near the secretory cells which lie in between the cortex and medulla)
  • Hypotension
  • Low Hct
• Erythropoiesis is inhibited by:
  • High red cell volume

Production of EPO is decreased in renal failure, which is why patients with end-stage renal disease require exogenous EPO.

Prostaglandins:

Production of prostaglandins esp PGE2 and prostacyclin – potent renal vasodilators

Bradykinin:

Production of bradykinin – potent renal vasodilator

RAAS

The RAAS is a signaling pathway involved in blood pressure control. It involves a number of hormones:

• Angiotensinogen is produced by the liver
• Renin is a protease enzyme (Half-life 80mins)
  • produced by the kidneys
  • stored by the granular cells of the juxtaglomerular apparatus, which lies close to the glomerulus and distal tubule
  • Secretion is stimulated by:
    • Pressure changes in the afferent arteriole
    • Stimulation of the macula densa when changes occur in tubular NaCl concentration
    • Renal sympathetic nerve activity (a direct β1 effect)
    • Baroreceptor reflexes
    • Negative feedback from AT II
  • Exists to cleave hepatic angiotensinogen to the 10-AA peptide angiotensin I
  • Note: Renin is rate-limiting step for activation of RAAS
• Angiotensin I
  • has mild vasoconstrictor properties, but not enough to cause significant changes in circulation
• Angiotensin Converting Enzyme (ACE)
  • Found mainly in pulmonary vascular endothelial cells – converts angiotensin I to angiotensin II
  • Also cleaves bradykinin into inactive metabolites
• Angiotensin II
  • Effects include a general reduction in sodium and water excretion, and maintenance of circulating blood volume, GFR and blood pressure.
  • Rapidly removed from circulation in 1-2mins, presumably by tissue peptidases (Angiotensinases)
• Aldosterone
  • is secreted from the zona glomerulosa of the adrenal cortex
  • It acts in the renal CCD to enhance the activity of ENaC and K+ secretion by principal cells.
  • increases Na⁺ (and water) reabsorption in exchange for K⁺ (kidney, gut, salivary, sweat)

JC 2019

Answer by JC