The Adrenal Gland Flashcards
Adrenal Gland Structure & Main Functions
- CONSISTS OF SEPARATE ENDOCRINE GLANDS IN 1 STRUCTURE
- ADRENAL MEDULLA (~25%) = MODIFIED SYMP. GANGLION DERIVED FROM NEURAL CREST CELLS○ SECRETES CATECHOLAMINES: EPINEPHRINE (ADRENALINE), NOREPINEPHRINE, DOPAMINE
1. MINERALOCORTICOIDS 2. GLUCOCORTICOIDS 3. SEX STEROIDS
Adrenal Cortex Structure + Hormones + Stimulation
Cortex surrounds medulla
Made of 3 concentric zones - all produce diff. hormones as they contain diff. enzymes
ZONA GLOMERULOSA = ALDOSTERONE
ZONA FASCICULATIS = CORTISOL
ZONA RETICULARIS = SEX HORMONES
ALL ARE STEROID HORMONES DERIVED FROM CHOLESTEROL - STIMULATED BY ACTH RELEASE
Hypothalamic-Pituitary-Adrenal Pathway Control
- LONG FEEDBACK LOOP = CORTISOL ON ANTERIOR PITUITARY (reduces ACTH) & HYPOTHALAMUS (reduces CRH, not as much)
- SHORT FEEDBACK LOOP = ACTH ON CRH
Congenital Adrenal Hyperplasia
• 21-HYDROXYLASE DEFICIENT = ALDOSTERONE & CORTISOL DFICIENT
○ SALT & GLUCOSE CONTROL DISRUPTED = cannot control BP & metabolise glucose ○ REDUCED CORTISOL REMOVES -VE FEEDBACK on ACTH & CRH = causes ++ACTH PRODUCTION = causes ENLARGEMENT of ADRENAL GLANDS ○ -VE FEEDBACK of ACTH on CRH RELEASE REMAINS ○ BABIES BECOME V. ILL W/I A FEW DAYS • ANDROGEN BIOSYNTHESIS UNAFFECTED (doesn’t depend on 21-hydroxylase) ○ ACCUMULATING STEROID PRECURSORS CHANNELLED INTO EXCESSIVE ANDROGEN PRODUCTION = can cause AMBIGUOUS GENITALIA (due to increased testosterone & oestrogen)
What is Cortisol & How does it act & how is it transported?
- GLUCOCORTICOID
- ~95% PLASMA CORTISOL BOUND TO CARRIER PROTEIN = CORTISOL BINDING PROTEIN
- ALL NUCLEATED CELLS HAVE CYTOPLASMIC GLUCORTICOID RECEPTORS
- HORMONE-RECEPTOR COMPLEX MIGRATES TO NUCLEUS & BINDS TO DNA via hormone-response element○ ALTERS GENE EXPRESSION, TRANSCRIPTION, TRANSLATION
Cortisol Secretion & Stimulation
- PLASMA LVLS = CHARACTERISTIC CIRCADIAN RHYTHM
- BURST OF CORTISOL PRECEDED BY BURSTS OF ACTH
- PEAK ~ 6-9am, NADIR ~ MIDNIGHT (peaks in the morning when waking)
- OTHER FLUCTUATIONS DURING DAY = EFFECTS OF OTHER STIMULI RELATED TO STRESS (gravity changes, increased glucose req. to overcome gravity, sudden increase in cognitive load - balance, stimuli, thinking)
- ACTH & CRH = also STIMULATED BY STRESS + ALCOHOL, SLEEP DEPRIVATION, CAFFEINE (as they depress neurones responsible for -ve feedback control)
Why is Cortisol & Aldosterone Essential for Life
Removal of adrenal glands = cannot deal w/ stress
Cortisol = essential for controlling [BG] = protects brain against hypoglycaemia as glucagon itself is not enough to deal w/ hypoglycaemia
Aldosterone = controls blood vol. & therefore BP
Primary Actions of Cortisol - Glucocorticoid Effects
- GLUCEONEOGENESIS (stimulates formation of gluconeogenic enzymes in liver)
- PROTEOLYSIS (stimulates breakdown of muscle protein to provide gluconeogenic substrates for liver - aids gluconeogenesis)
- LIPOLYSIS (stimulates lipolysis in adipose tissue - increases free FA & ketones + provides glycerol for gluconeogenesis)
- DECREASES INSULIN SENSITIVITY (of muscles & adipose tissue)
Additional Actions of Cortisol - Non-Glucocorticoid Effects
- -VE EFFECT ON Ca2+ BALANCE (decreases absorption in kidney, increases excretion at kidney & bone resorption - osteoporosis)
- IMPAIRED MOOD & COGNITION (depression & impaired cognitive function strongly ass. w/ hypercortisolaemia)
- PERMISSIVE EFFECT ON NOREPINEPHRINE (particularly in vascular SM = alpha-receptor effect of vasoconstriction - impact BP)
- SUPRESSES IMMUNE SYSTEM (cortisol reduces lymphocyte count, reduces antibody formation, inhibits inflammatory response; can be useful clinically e.g. in asthma, UC, organ transplants)
a. Glucocorticoids inhibit gene that codes for enzymes responsible for creating inflammatory proteins/markers
Glucocorticoid Therapy Side Effects + Why Should They be Weaned Off?
- LIPOLYSIS = LOSS OF PERCUTATEOUS FAT - APPEARANCE OF THINNING SKIN = MORE FRAGILE
- PROTEIN CATABOLISM = INCREASED RISK OF INFECTION, MUSCLE WASTING
- SUPPRESSES IMMUNE SYSTEM = INCREASED SECERITY & FREQ. OF INFECTION
- EXOGENOUS CORTISOL = ENHANCED -VE FEEDBACK CONTROL ON CRH & ACTH
- LOSS OF TROPHIC ACTION OF ACTH ON ADRENAL GLAND = ATROPHY OF GLAND○ RISK OF ADRENAL INSUFFICIENCY IF WITHDRAWAL TOO FAST
Aldosterone - What is it & secretion control?
- MINERALOCORTICOID = ACTS ON DISTAL TUBULE OF KINDEY TO DETERMINE LVLS OF MINERALS REABSORBED/EXCRETED & therefore H2O
- INCREASES REABSORPTION OF Na+ & PROMOTES EXCRETION OF K+○ THUS CONTROLS BP
CONTROLLED BY RAAS
Adrenal Medulla
- MODIFIED SYMP. GANGLION
- PREGANGLIONIC SYMP. FIBRES TERMINATE ON SPECIALISED POSTGANGLIONIC CELLS IN ADRENAL MEDULLA
- THESE POSTGANGLIONIC FIBRES DON’T HAVE AXONS - RELEASE NEUROHORMONE DIRECTLY INTO BLOOD
Pheochromocytoma
• NEUROENDOCRINE TUMOUR of ADRENAL MEDULLA = results in EXCESS CATECHOLAMINES
○ CATECHOLAMINES = INCREASES HR - INCREASES CO - INCREASES BP ○ DIABETOGENIC = ADRENERGIC EFFECT on GLUCOSE METABOLISM (permissive effects on glucagon) • RESPONDS WELL TO SURGERY
Cushing’s Disease
Hypersecretion of cortisol:
Cushing’s syndrome/disease = Hypersecretion is most commonly due to a tumour in adrenal cortex/pituitary gland (most common + excess ACTH)
Iatrogenic = Too much cortisol administered therapeutically
Hyposecretion of cortisol:
Less common than hypersecretion
Addison’s disease = Hyposecretion of all adrenal steroid hormones + Due to autoimmune destruction of adrenal cortex
Cushing’s Disease
• FAT DEPOSITION IN TRUNK, BASE OF NECK AT THE BACK, IN THE FACE (MOON FACE)
○ AT EXPENSE OF WASTING OF EXTREMITIES/LIMBS * ASS. W/ HYPERTENSION (due to hypercortisolaemia) * CORTISOL = COUNTER-REGULATORY TO INSULIN ⸫ EXCESS CORTISOL = DIABETOGENIC
