PL4 Adrenal Cortex

• Adrenal Cortex

  The outer part of the adrenal gland that produces steroid hormones

  
• Adrenal Cortex


  • Produces steroid hormones
  • Includes zona glomerulosa, zona fasciculata, and zona reticularis

  
• Adrenal Medulla


  • Produces catecholamines like epinephrine and norepinephrine
  • Only part of the adrenal gland that is derived from neural crest cells

  
• Paraganglia


  Groups of cells resembling those in the adrenal medulla, found near thoracic and abdominal sympathetic ganglia
• Biosynthesis of Corticosteroids

  Cholesterol (27C) -> Pregnane Derivatives (21C) -> Androstane Derivatives (19C) -> Estrane Derivatives (18C)
• Zona Glomerulosa


  Only zone that can produce aldosterone, lacks 17α-hydroxylase

  
• Angiotensin II


  Binds to AT1 receptor, activates phospholipase C and protein kinase C, facilitates action of aldosterone synthase

  
• Zona Fasciculata and Zona Reticularis

  Produce glucocorticoids and adrenal androgens
• Natural Corticosteroids

  • Cortisol (highest glucocorticoid activity)
  • Corticosterone
  • Aldosterone (most potent mineralocorticoid)
  • Deoxycorticosterone
• Synthetic Corticosteroids

  • Prednisolone
  • 9-Fluorocortisol
  • Dexamethasone

  
• Adrenal Insufficiency

  Leads to water intoxication due to increased vasopressin and decreased glomerular filtration rate
• Glucose infusion in adrenal insufficiency

  Can lead to glucose fever, collapse and death due to metabolized glucose diluting the plasma and swelling of thermoregulatory centers
• Glucocorticoids prevent excessive stress-induced changes, but long-term high levels lead to Cushing's Syndrome

  
• Catecholamines


  • Maintenance of vascular reactivity
  • Free Fatty Acid mobilizing for emergency energy supply

  
• Glucocorticoids


  Prevent excessive stress-induced changes
• ↑ ACTH: short term

  Beneficial
• ↑ ACTH: long term

  Harmful & disruptive → Cushing Syndrome

  
• Cushing Syndrome


  1. Stimulate adrenal gland

  2. Release cortisol
• Dopamine


  For CNS system
• Permissive Action of Glucocorticoids


  Small amounts are essential for a number of metabolic reactions although they do not produce these effects
• Permissive Action of Glucocorticoids

  • Calorigenic effects: glucagon & catecholamines
  • Necessary for glucagon to exert its gluconeogenic action during fasting
  • Necessary for catecholamines to exert lipolytic effects, pressor responses, bronchodilation

  
• Increased metabolic rate results in increased oxygen consumption by cells and more heat generated
• Effects of Glucocorticoids on Vascular Reactivity

  • In adrenal insufficiency: Vascular smooth muscles unresponsive to norepinephrine
  • Capillaries dilate & terminally become permeable
  • Impaired vascular compensation for hypovolemia
  • Promotes vascular collapse
  • Glucocorticoids restore vascular reactivity
• Vascular reactivity

  Responsiveness of blood vessels to specific stimulus
• In adrenal insufficiency: EEG waves slower than normal α rhythm, mild personality changes (irritability, inability to concentrate, apprehension) reversed only by glucocorticoids
• Effects of Glucocorticoids on Blood

  • Reduce number of circulating lymphocytes, monocytes & eosinophils
  • Total blood count is increased due to increased levels of neutrophils
  • RBCs & platelets are increased as well

  
• Anti-inflammatory Effects of Cortisol

  • Stabilises lysosomal membranes so inhibits release of proteolytic enzymes
  • Decreases capillary permeability thereby inhibiting diapedesis
  • Decreases both migration of WBCs into the inflamed area and phagocytosis of the damaged cells
  • Suppresses immune system, causing lymphocyte reproduction to decrease
  • Attenuates fever by reducing release of interleukin-1 from WBCs
  • Causes resolution of inflammation in rheumatoid arthritis, rheumatic fever, acute glomerulonephritis
• Glucocorticoids given to children in caution as they can even reduce fever
• Anti-allergic Effects of Glucocorticoids

  • ↓ release of secretory products of granulocytes, mast cells & macrophages
  • ↓ levels of serotonin and hydrolases thereby ↓ allergic & inflammatory responses in tissues

  
• Anti-immunity Effects of Glucocorticoids

  • ↓ circulating Basophils, Eosinophils & T lymphocytes
  • ↓ production & release of cytokines suppresses cell mediated immunity
  • Involution of lymph nodes, thymus & spleen → ↓ antibody production
• Renal Effects of Glucocorticoids

  • Restore GFR & renal plasma flow to normal levels following adrenalectomy
  • Facilitate free water & uric acid excretion
• Gastric Effects of Glucocorticoids


  • ↑ gastric flow & gastric acid secretion but ↓ gastric mucosal cell proliferation → to peptic ulceration following chronic cortisol treatment

  
• Other Effects of Glucocorticoids


  • During Fetal life: accelerate maturation of surfactant
  • Decrease: Growth Hormone secretion & TSH secretion
  • Induce PNMT (Phenylethanolamine N-methyltransferase)

  
• Best time to give glucocorticoids is after breakfast around 8am to follow the normal circadian pattern
• Antigrowth Effects of Corticosteroids

  • Suppress somatic growth by: ↓ growth hormone (GH) secretion & inhibiting anabolic effects of GH & IGF-1
  • Cause osteoporosis by: ↓ absorption of calcium from GIT by antagonising effects of active vitamin D, inhibiting mitosis of fibroblasts, causing degradation of collagen
  • Delay wound healing by: reduction of fibroblast proliferation & ↓ quality & strength of connective tissue
  • Cause muscle weakness & atrophy
• Circadian / Diurnal Rhythm

  ACTH secreted in irregular bursts, most frequent in the early morning (75% cortisol production occurs between 4:00 - 10:00 am), least frequent in the evening
• Corticosteroids Derivatives

  1. pregnane derivatives -> progesterone corticoids
  2. androstane derivatives -> androgens
  3. estrane derivatives -> estrogen
• Steroidogenesis


  ***

  
• Zona fasiculata & zona reticularis

  formation

  
• Action of mineralocorticoids

  1. primary function = defense of intravascular volume, increase reabsorption of Na+ in urine, sweat, saliva, colon
  2. retention of Na+ in ECF -> increase ECF volume
  3. Mechanism = increase transport of ENaCs from cytoplasm to cell membrane

  • kidney = Principal cell (P) of collecting duct helps increase Na+ enchange for K+ -> K+ diuresis
  • H+ -> increase urine acidity