Physiology notes

1. ADRENAL CORTEX 2
Dr.Fathima Fazna.P
Assistant Professor
Dept. of Physiology

2. Glucocorticoids - MOA,
regulation & actions

3. Mechanism of action

5. Mechanism of action
• Bind with cytoplasmic receptor
• Activated hormone - receptor complex enters nucleus
• Binds to specific DNA binding sites (Hormone response
element)
• Transcription of specific genes to form mRNA
• mRNA moves into cytoplasm
• Translation of proteins
• Altered cell function

6. Regulation of glucocorticoid secretion
Hypothalamus
Anterior Pituitary
Adrenal cortex
Cortisol
CRH
ACTH
Emotions Stress
Diurnal variations

7. ACTH
• Secreted by corticotrophs of anterior pituitary
• Synthesized as pro-opiomelanocortin & is cleaved to form
ACTH
• In intermediate lobe POMC form α- MSH
• ACTH contains α- MSH sequence at N terminal

8. • Secreted as irregular bursts
• More in early morning hours (75% of secretion)
• Secretion rises at 4 am & peak between 7- 10 am
• Minimal at midnight
• Called as diurnal variation/circadian rhythm
• Due to natural sleep-wake cycle controlled by biological
rhythm of suprachiasmatic nucleus of hypothalamus

9. Mechanism of action: by increasing cAMP
Functions:
• Stimulates synthesis & secretion of steroids especially
glucocorticoids
• Hypertrophy of adrenal cells
• Intrinsic MSH activity (Hyperpigmentation in high ACTH
secretion - Give physiological basis)
• Acts as neurotransmitter in brain & GIT
• Controls secretion of cytokines from lymphocytes

10. Actions of glucocorticoids

11. Effects of
Glucocorticoids
Blood
cells
GIT,
kidney
Bone,
muscle
Anti-
inflammatory
Anti-allergic
Permissive
action
Metabolism
cvs
Connective
tissue
CNS

12. 1. Metabolism
2. Muscle
3. Bone
4. Connective tissue
5. Blood cells
6. Kidney
7. CNS
8. CVS
9. GIT
10.Permissive action
11.Fetus
12.Anti inflammatory & anti allergic action
13.Immune system
14.In stress

13. 1. Metabolism
Carbohydrate metabolism
a. Increases gluconeogenesis in liver
b. Anti-insulin action: on muscle & adipose tissue
Prevent glucose uptake by delaying the rate of glucose utilization
c. Increases glycogenolysis
d. Increases secretion of glucagon & epinephrine
• Glucocorticoids are essential for survival during fasting

14. Adrenal diabetes
• Increases blood glucose level: Increases gluconeogenesis &
decreases utilization of glucose by cells
• Increases plasma level insulin - not effective like under normal
condition
• Cortisol reduces sensitivity of muscle & adipose tissues to
stimulatory effects of insulin

15. Protein metabolism
• Proteolytic effect: in all body cells except liver
• Increased protein synthesis: in liver & increases plasma protein

16. Fat metabolism
• Lipolytic & ketogenic effect
• Promotes mobilization of free fatty acids from adipocytes
• Increase absorption of fat
• Increases plasma free fatty acids
• Enhances oxidation of fatty acids in the cells for energy

17. On food intake & fat distribution
• Increases appetite & food intake by stimulating
Neuropeptide Y secretion
• Stimulates differentiation of preadipocyte to adipocyte
• Stimulates lipogenesis in some parts of body by activating
lipoprotein lipase & glucose 6 phosphate dehydrogenase
activity of adipocytes
• Excess cortisol causes maldistribution of fat resulting in
truncal obesity, moon face, pendular abdomen & buffalo
hump with thinning of extremities (Give physiological basis)

18. 2. Effect on muscle
• Maintains contractility & work performance of skeletal and
cardiac muscle
• Excess cortisol - proteolysis & decreased muscle mass

19. 3. Effect on bone
• Increases bone resorption by increasing osteoclastic activity
• Decreases intestinal absorption of Ca2+
• Increases renal Ca2+ excretion
• Inhibit bone formation by decreasing collagen synthesis &
inhibit osteoblasts
• Decreases synthesis of vitamin D
• Increased cortisol - osteoporosis, loss of bone mass (Give
physiological basis)

20. 4. Effect on connective tissue
• Decreases collagen synthesis & fibroblast proliferation
• Thinning of skin & capillary walls
• Intracutaneous hemorrhage due to rupture of fragile capillaries
• Excessive amounts of cortisol makes the skin very thin & is more
readily damaged
• Connective tissue support of capillaries is impaired & capillary injury
or bruising is increased

21. 5. Blood cells
• Lymphocytopenia
• Inhibits lymphocyte mitotic activity
• Prevents: T cell proliferation (decrease cytokine secretion)
• Increased sequestration into reticulo-endothelial system – spleen &
bone marrow
• Atrophy of lymphoid tissue
• Eosinopenia
• Stimulates apoptosis
• Increased sequestration into spleen & lungs
• Inhibit release of cytokines needed for eosinophil growth
• Basopenia
• Increase neutrophils, RBCs & platelets

22. 6. Effect on kidney
• Increases GFR & water clearance
• Increases phosphate excretion
✓Patients with adrenocortical insufficiency cannot excrete water load
✓Sudden infusion of large volume of saline or glucose may result in
water intoxication
✓Plasma becomes hypo osmolar due to hemodilution
✓Cells in brain swells that impairs hypothalamic thermoregulatory
centers
✓Patients develop high fever & collapse

23. 7. Effect on CNS
• Modulates excitability, behaviour & mood of individuals
• Corticoid therapy in neonates - inhibit CNS cell proliferation &
interfere with synapse formation
• Excess cortisol - precipitate fits, psychosis
• Deficiency - personality changes

24. 8. Effect on CVS
• On heart- increases myocardial performance
• On blood vessel
• Maintains vascular reactivity & normal blood pressure
1. Inhibits Na-Ca exchanger & thus increases Ca in blood vessel
smooth muscle
2. GC sensitizes arterioles to the constrictor action of catecholamines
3. Inhibits COMT which causes breakdown of catecholamines
4. Enhances catecholamine synthesis
5. Decreases release of vasodilators like prostaglandins

25. Adrenal insufficiency
• Blood vessel become unresponsive to catecholamines
• Produce vasodilation & vascular collapse
• Injection of cortisol is a must in shock along with catecholamines