LECTURE 4 (Adrenal glands) Flashcards
(37 cards)
Describe the Adrenal gland
- Adrenal medulla = functionally related to the sympathetic nervous system + secretes epinephrine and norepinephrine
- Adrenal cortex = secrete corticosteroids (hormones derived from cholesterol)
What are the three distinct layers of the Adrenal cortex?
- ZONA GLOMERULOSA (15%) = secrete aldosterone, contain aldosterone synthase, controlled by extracellular fluid concentrations of ANGIOTENSIN II and K+
- ZONA FASCICULATA (75%) = secrete glucocorticoids (cortisol + corticosterone) and adrenal androgens + oestrogens, secretion controlled by hypothalamic-pituitary axis via ACTH
- ZONA RETICULARIS = secrete adrenal androgens (DHEA and androstenedione), small amount of oestrogen’s and glucocorticoids
What causes hypertrophy of zona glomerulosa, zona fasciculata & zona reticularis?
zona glomerulosa = angiotensin II
zona fasciculata + zona reticularis = ACTH
Describe how cholesterol is provided by LDLs in the adrenal gland
1) LDLs diffuse from plasma into interstitial fluid and attach to specific receptors contained in structures called “coated pits” on adrenocortical cell membranes
2) Coated pits are internalised by endocytosis -> form vesicles that fuse with cell lysosomes + release cholesterol
3) Free cholesterol delivered to mitochondria where it is cleaved by CHOLESTEROL DESMOLASE to form PREGNENOLONE (rate-limiting step!!!!)
4) In three zones, different factors affect cholesterol conversion
Which plasma proteins can adrenocortical hormones bind to?
- Cortisol-binding globulin
- Transcortin
- Albumin
Adrenal hormones binding to plasma proteins form a reservoir, what is the importance of this reservoir?
- Lessen rapid fluctuations in free hormone concentrations
- Ensure a relatively uniform distribution of the adrenal hormones to the tissues
How does the liver metabolise Adrenocortical hormones?
- Conjugated to glucuronic acid or sulfates
- Some conjugates excreted in bile
- Some conjugates enter circulation but aren’t bound to plasma proteins -> filtered out by kidneys -> excreted in urine
What is Mineralcorticoid Deficiency?
Total loss of mineralcorticoids secretion which causes K+ concentration of extracellular fluid to rise markedly, Na2+ and Cl- to be rapidly lost from body and total extracellular fluid and body volume to greatly reduce
MANIFESTATIONS:
- Diminished cardiac output -> shock -> death
TREATMENT:
- administration of aldosterone/mineralcorticoid
- extensive salt therapy
What is the effect of Aldosterone?
Increases reabsorption of sodium and simultaneously increases secretion of potassium by renal tubular epithelial cells -> increases Na+ in extracellular fluid and decreases K+
[IT IS A SODIUM-RETAINING HORMONE]
What happens when there is excess aldosterone?
When Na+ is reabsorbed by tubules, there is a simultaneous osmotic absorption of water -> small increase in ECF Na+ concentration stimulate thirst and increased H2O intake -> Rise in arterial pressure increases kidney excretion of both salt and H2O (PRESSURE NATRIURESIS and PRESSURE DIURESIS) -> salt and water concentration go back to normal (ALDOSTERONE ESCAPE)
What happens when aldosterone secretion becomes zero?
Large amounts of salt are lost in the urine -> diminishes sodium chloride in ECF and decreases ECF volume -> severe ECF dehydration and low blood volume -> circulatory shock
What does excess aldosterone and too little aldosterone cause?
- Excess aldosterone = Hypokalaemia
[severe muscle weakness develops due to alteration of the electrical excitability of the nerve and muscle fibre membranes] - Too little aldosterone = Hyperkalaemia
[cardiac toxicity, weakness of heart contraction, development of arrhythmia and heart failure]
How does excess aldosterone cause alkalosis?
Aldosterone causes secretion of hydrogen ions in exchange for sodium in the intercalated cells of the cortical collecting tubules -> decreases H+ concentration in ECF causing metabolic alkalosis
What is the effect of aldosterone on other parts of the body?
- Sweat glands = conserve body salt in hot environments
- Salivary glands = conserve salt when excessive quantities of saliva are lost
- Colon = prevent loss of sodium in stools (loss will lead to diarrhoea)
Describe sodium reabsorption
1) Aldosterone diffuses readily to the interior of the tubular epithelial cells
2) In the cytoplasm of the tubular cells, aldosterone combines with a highly specific cytoplasmic MINERALCORTICOID RECEPTOR
3) Aldosterone-receptor complex diffuses into the nucleus, inducing one or more specific portions of DNA to form one or more types of mRNA related to sodium and potassium transport
4) mRNA diffuses back into cytoplasm to ribosome to form proteins
- enzymes
- membrane transport proteins
What are the four factors known to play essential roles in the regulation of aldosterone?
- Increased K+ concentration in the extracellular fluid greatly increases aldosterone secretion
- Increased angiotensin II concentration in the ECF increases aldosterone secretion
- Increased Na+ concentration in the extracellular fluid very slightly decreases aldosterone secretion
- ACTH from the pituitary gland is necessary for aldosterone secretion but has little effect in controlling the rate of secretion in most conditions
[the strongest in factors in regulating aldosterone secretion are POTASSIUM ION CONCENTRATION and RENIN-ANGIOTENSIN SYSTEM]
How does aldosterone act on the kidneys?
- To help them excrete the excess potassium ions
- To increase the blood volume and arterial pressure -> returning the renin-angiotensin system towards its normal level of activity
How does Cortisol stimulate gluconeogenesis?
- Increases the enzymes required to convert amino acids into glucose in the liver cells (by activating DNA transcription in the liver cell nuclei to form enzymes)
- Causes mobilisation of amino acids from the extrahepatic tissues (more amino acids available in plasma to enter into gluconeogenesis)
How does cortisol decrease the rate of glucose utilisation in most cells of the body?
Glucocorticoids (e.g cortisol) depress the oxidation of NADH to form NAD+ which must be oxidised to allow for glycolysis
What happens to the blood glucose concentrations because of cortisol?
Blood glucose concentrations rise
Explanation: Due to increased rate of gluconeogenesis and the moderate reduction in the rate of glucose utilisation. If the concentration is great enough it is called “Adrenal diabetes”
How does Cortisol cause a reduction in cellular protein?
- Decreased protein synthesis
- Increased catabolism of protein already in the cells
CAUSES:
- decreased amino acid transport into extra hepatic tissues
- depressed formation of RNA and subsequent protein synthesis in many extra hepatic tissues
[This happens to everywhere in the body APART FROM THE LIVER!!!! IT ENHANCES LIVER PROTEINS]
What effects does cortisol have on the liver proteins?
- Increased rate of deamination of amino acids by the liver
- Increased protein synthesis in the liver
- Increased formation of plasma proteins by the liver
- Increased conversion of amino acids to glucose (gluconeogenesis)
How does cortisol cause mobilisation of free fatty acids?
There is a diminished transport of glucose into fat cells -> alpha-glycerophosphate derived from glucose is required for maintenance of triglycerides -> absence causes fatty acid release -> increased mobilisation of fats + increased oxidation of fatty acids, shifts metabolic systems to utilisation of fatty acids
What type of Obesity is caused by excess cortisol?
Excess deposition of fat in the chest and head regions giving a buffalo-like torso and a rounded “moon face”
CAUSE: fat is generated in some tissues of the body more rapidly than it is mobilised and oxidised
