Adrenal Gland Flashcards
Which adrenal gland is larger?
Left
What vessel crosses the adrenal gland?
Phrenicoabdominal trunk
What is the cortex?
Pale yellowish outer part
What is the adrenal medulla?
Dark brown inner part
Which part of the adrenal gland can regenerate following injury?
Adrenal cortex. The medulla is of neural origin so it does not regenerate
Where is the Zona glomerulosa?
Superficial part of cortex
What does the Zona glomerulosa make?
Mineralocorticoids
What does the Zona fasciculata produce?
Glucocorticoids
What does the zona reticularis produce?
Sex hormones
Which parts of the cortex are responsive to ACTH
Zona fasciculata and reticularis
What happens to the cortex if there is a loss of ACTH?
Cortex gets thinner
What is general adaptation syndrome?
Non-specific response to injury or stress. Causing enlargement of the adrenal gland. ZG is not affected
What hormones are derived from cholesterol?
Adrenocortical hormones (C21)
What is the source of cholesterol?
- Synthesis in adrenal cortex
- Plasma LDL cholesterol
Where is the OH in mineralcorticoids?
C11
Where is the OH groups in glucocorticoids?
C11, C17
What are the carrier proteins for glucocorticoids?
- Transcortin (75%)
- Albumin(15)
- Free (10%)
What are the carrier proteins for mineralcorticoids?
- Albumin (50%)
- Transcortin (10%)
- Free (40%)
What could effect carrier protein levels?
Liver damage
What synthesizes carrier proteins?
Liver
What is the adrenarche?
Region of the zona reticularis that changes during puberty in some animals
Where are the recognition methyl groups in corticoids?
19,18,21
What does corticotropin do in the adrenal gland?
Activates the pathway of the metabolism of cholesterol to either mineral or glucocorticoid depending on the cell it is going through
What are two location of the cellular location of enzymes in the cholesterol pathway?
- Mitochondria
- SER
Which adrenal hormone has a higher concentration in the blood?
Cortisol (10fold higher)
What is the half-life of cortisol?
60min
What is the half-life of aldosterone?
20min
The total glucocorticoid in the blood depends on what?
- Secretion rate
- Metabolism
- Amt of carrier protein
What metabolizes steroids?
Reduction to water soluble by glucuronides in the liver and then excreted in the urine
What is the most potent mineralcorticoid?
Aldosterone
How do you prevent overstimulation of aldosterone receptor by cortisol?
11-B-hydroxysteroid dehydrogenase converts cortisol to inactive cortisone
What are the physiological actions of aldosterone?
- Incr Na reabsorption
- Incr angiotensin II production
- Decr. potassiom by renal excretion
- Conservation of water
What is the behavioral actions of aldosterone?
With Angiotensin II drives salt-seeking behavior
How do you regulate aldosterone?
- Plasma potassium will stimulate aldosterone
- Angiotensin Ii stimulates it
- Poorly regulated by ACTH
- Suppressed by atrial natriuretic facto
- High Na and low K decrease aldosterone
What is the angiotensin cascade?
Renin is released from the kidney due to hypotension. This combined with angiotensinogen from the liver converted to AGT I. AGT 1 to AGT II by ACE. This no goes to the adrenal gland and promotes aldosterone secretion
Where in the kidneys does aldosterone and AGTII act?
- Distal tubule
- Collecting duct
What are the effects of aldosterone in the kidney?
- Na and water get reabsorbed
- K is excreted
What is the most important glucocorticoid?
Cortisol
What are the effects of Cortisol?
- Stimulate gluconeogenesis
- incr blood glucose
- Anti insulin effect - Protein and fat catabolism
- Redistribution of body fat
- Water and electrolyte distribution
- Trace mineral distribution
- Blocks inflammatory response
- Suppresses immune system
What are the effects of stimulating protein and fat catabolism?
- Negative nitrogen balance, urinary loss of nitrogen
- Mobilize metabolism of fatty acid
Where is fat redistributed if over exposed to cortisol?
Moved from the extremities and SQ abdominal sites to pelvis, neck, thorax, liver, and omentum
What are clinically important uses of glucocorticoids?
- Block inflammatory responses
- Suppress immune system
What is the rate limiting step in cortisol regulation?
ACTH increases cholesterol and you get pregnenolone conversion
What regulates release of ACTH?
- Vasopressin
- CRH
- Sleep
- Stress
- Diurnal rhythm
What other hormones does glucocorticoid have permissive effects on?
- Glucagon in the liver
- Catecholamines
How can you test function of adrenocortical function?
- Plasma cortisol
- ACTH response test
- Dexamethasone suppression test
How do you perform a dexamethasone suppression test?
Dex is a synthetic glucocorticoid and when administered and doesn’t interfere with plasma cortisol. Should see a decrease in cortisol because of the negative feedback
How to differentiate hyper aldosteronism and hyperadrenocorticism?
Should see an increase in Ang II if it is hyperaldosteronism
What is the classic triad for dogs with hyperadrenocorticism?
- PD/PU
- Pendulous abdomen
- hepatomegaly
- abdominal weakness - Bilateral alopecia
What is the hallmark sign of hyperadrenocorticism in cats?
Thin skin
What is the hallmark of horses with hyperadrenocorticism?
- Long hair coat out of season
- Laminitis
- Weight loss
- PD
- Muscle wasting
What are the effects of cushing’s on the liver?
- Fat deposited on abdominal viscera
- Fatty liver disease
- High activity of 11-beta HSD type 1 in liver and visceral fat. Allows for inhanced inflammation of abdominal viscera
- increases fibrosis and hepatic cancer risks
What is the effects of cushing’s on bone?
- Decrease osteoblast
- Increase osteoclasts
- Bone metabolism on resorption
- apoptosis of mature osteoblasts and osteocytes
- delayed maturation
- Less GI calcium absorption
- increases PPAR gamma 2
- Suppress BMP2
- decrease growth hormone effect
How does Mitotane help manage hyperadrenocorticism?
Kills rapidly dividing cells to suppress cancer.
-will produce necrosis of the zona fasciculata and reticularis
How does trilostane help HAC?
Inhibits 3 beta hydroxysteroid dehydrogenase
How does ketoconazole help HAC?
Blocks synthesis of cortisol
How does L-deprenyl help HAC?
Inhibit dopamine degradation so more dopamine to inhibit glucocorticoid release
What can cause hypoadrenocorticism?
- Lymphatic infiltration of adrenal cortex
- Secondary to mitotane treatment
- Autoimmune destruction of adrenal cortex
- Secondary lack of CRH or ACTH
What are some signs of hypoadrenocorticism (Addison’s like syndrome)?
- Hyperkalemia (arrhytmias)
- Hyponatremia
- Muscle atrophy, depression weight loss
- Brady cardia and widened QRS complex
- Hypotension
How is the adrenal medulla oriented?
Deep in adrenal with an extensive of vascular system that flows from the cortex to the medulla.
What does the Adrenal medulla produce?
Catecholamines
- Epinephrine
- Norepinephrine
What innervates the adrenal medulla?
Preganglionic sympathetic fibers. Splanchnic nerve (T12, T13, L1)
How are catecholamines produced?
Tyrosine is key precursor. Epinephrine can only be made in chromaffin cells
How are catecholamines stored?
Cytoplasmic granules
How is epinephrine carried?
Free (50%)
Albumin (50%)
What can modulate release of catecholamines?
Glucocorticoids that flow in and causes disinhibition
What can inhibit synthesis of catecholamines?
- NE
- EPI
What is the rate limiting step of the synthesis of catecholamines?
Hydroxylation of tyrosine
What mediates the actions of catecholamines?
- alpha- and beta-adrenergic receptors
- alpha receptors (vasoconstriction)
- beta receptors (Increase HR, vasodilation by Epi)
What is part of the regulation of release of catecholamines?
- Sympathetic preganglionic neurons (Ach)
- Cortisol
- Stress or hypoglycemia
