What is the blood supply of the adrenal glands?
Aorta --> phrenic and renal arteries:
renal arteries --> inferior adrenal arteries --> adrenal glands
phrenic --> suprarenal arteries --> adrenal glands
What is the embryological origin of the adrenal glands?
Medulla - neural crest ectoderm
Cortex - intermediate mesoderm
What are the zones of the adrenal cortex?
Zona Glomerulosa - "Salt"
Zonal Fasiculata - "Sugar"
Zona Reticularis - "Sex"
What does the medulla make and why is the blood flow critical for this?
Medulla makes epinephrine, which requires large amounts of cortisol
--> blood flow in the adrenal allows cortisol from the cortex to be brought to the medulla
What is the role of the zona fasiculata?
Synthesize glucocorticoids (esp. cortisone)
Regulates glucose synthesis, storage, usage
(look "foamy" histologically due to many lipid droplets)
What is cortisol?
glucocorticoid that mobilizes glucose and free fatty acids
Made in adrenal cortex
What is aldosterone?
Mineralcorticoid that stimulates Na reabsorption in the kidney
Made in Adrenal cortex
What is Dehydroepiandosterone Sulfate?
DHEA = Androgen
of weak action
Made in adrenal cortex
What is the hypothalmic puitary adrenal axis?
Hypothalmus releases CRH, activating ACTH release from pituitary to activate the adrenal gland into producing cortisol (which inhibits ACTH release), etc.
--> This axis is driven by:
Stress (which can override negative feedback)
--> Epi and VP increase anterior pituitary sensitivity to CRH
What are the 4 dominant mechanisms of secretory control of ACTH?
1. Negative feedback regulation
Cortisol inhibits ACTH release
2. Episodic (pulsitile) secretion
3. Diurnal rhythm
Epi and VP increase sensitivity of ant. pit. to CRH
How is cortisol degraded?
Make it water soluble so it is released through the urine
What does cortisol do?
Anabolic (on liver) and catabolic (other organs) actions
--> allows fasting for days to weeks
--> shifts the peripheral body over to ketone bodies and AAs and turns gluconeogensis on in the liver to make glucose for the brain
--> Down regulates insulin receptors on the peripheral organs so they don't use glucose
**That's why Cushing's leads to significant weight gain and insulin resistance (diabetes)
What are the effects of cortisol on the Immune System in high dose?
- Stabilizes lysosomal membranes
- Decreases capillary permeability
- Dpresses white cell proliferation and phagocytosis
- Inhibits local accumulation of white cells
- Reduces proliferation of fibroblasts
- Prevents degranulation of mast cells
- Inhibits cytokine production/signaling
What are effects of cortisol on the cardiovascular system?
Central nervous system?
Cardiovascular = increases vascular tone
CNS = euphoria
Fetus = surfactant
Fetal adrenal gland starts working ~2weeks prior to partruition
What are causes of cortisol excess?
Primary Cushing's - adrenal
Secondary Cushing's - pituitary
Tertiary Cushing's - hypothalamus
Ectopic ACTH - often small cell carcinoma of the lung
Iatrogenic - pharmaceutical
What is the difference of Cushing's Disease and Cushing's Syndrome?
Disease has set point for negative feedback operating, but is set too high for good health
All other forms of Cushing's syndrome lack any form of set point regulation
(Cushing's disease is a subset of Cushing's syndrome)
What causes the striae of Cushing's syndrome?
Increased deposition of fat and breakdown of collagen
They are purple due to vasculature being more visible
What are symtpoms of Cushing's syndrome?
How do you diagnose the cause of Cushing's syndrome?
What causes the skin bronzing of Cushing's syndrome?
High levels of ACTH
- ACTH acts like melanin, but is usually in too low of levels because it's very weak
What is hypocortisolism? What are the types?
A state of cortisol deficiency
Primary hypocortisolism: Addison's diseaes
Hypocortisolism due to adrenal destruction
Secondary hypocortisolism: Sheehan's disease
Failure of pituitiary gland to produce ACTH
Failure of the hypothalamus to produce CRH
How is aldosterone regulated?
1. Renin-Angiotensin-Aldosterone System
2. Serum potassium primarily
3. ACTH to a lesser degree
What is the action of aldosterone?
Acts on the kidney to actively absorb Na and increase K and H secretion
--> not effective when tubular Na is reduced (i.e. dietary Na restriction)
How does salt ingestion affect the RAAS?
Intake of Na load --> increase blood Na (hypernatremia) --> Decreased secretion of Aldosterone (via renin-angiotensin) --> decreased reabsorption of Na and increased reabsorption of K --> uptake of K into cells to maintain normal blood levels --> Restoration of blood Na as Na load passes --> aldosterone secretion restored to normal rate --> Na reabsorption increases to normal rate --> K excretion increases to pass the extra taken up into cells
What are the functional components of the JG apparatus?
- Baroreceptor (releases renin at low volume, low pressure)
- Chemosensor (releases renin at low osmolarity - low Na+, K+)
- Neuroendocrine transducer
What are two major forms of aldosterone excess?
Acites (fluid leakage into thoracic/abdominal cavity)
Adrenal driven to increase aldosterone due to H2O loss
Renin is activated
What are results of hyper aldosteronism?
Hypernatremia (due to increased Na reabsorption)
--> increased plasma volume
--> Suppresed RAAS
Hypokalemia (due to increased K excretion)
--> Weakness and paralysis
--> Metabolic alkalosis (increased H+ secretion)
How does Primary Hyperaldosteronism affect:
Effective arterial blood volume
Total body fluid volume
How does renal artery stenosis affect RAAS?
They have a severely increased RAAS output due to restriction of blood flow to JGA
--> leads to life threatening HTN
What is congenital adrenal hyperplasia?
Commonly: 21-Hydroxylase deficiency
Hyperplasia of adrenal gland --> increased DHEA production
Can cause virilization in females, precocious puberty in males
Aldosterone and Cortisol are not produced due to enzyme deficiency
--> life threatening levels of Angiotensin II cause vasoconstriction and high BP
What are chromaffin cells?
Cells in the medulla of the adrenal gland that synthesize, store, secrete catecholamines: NE and Epi
- Conversion of NE to Epi depends on Phenylethanolamine-N-methyltransferase enzyme
What do the catecholamines produced by the adrenal medulla affect the body?
1. Cardiovascular system - increased cardiac output
2. Metabolic function - fuel mobilization
3. Arousal - heightened awareness
What is the biochemical process of catecholamine production?
Tyrosine --> Dopa
Enzyme: tyrosine hydroxylase
Dopa --> Dopamine
Enzyme: Aromatic L-amino Acid Decarboxylase
Dopamine --> NE
Enzyme: Dopamine hydroxylase
NE --> Epi
What are clinical features of pheochromocytoma?
Hypertension due to extreme amounts of catecholamines
Symptoms during or following paroxysms:
Forceful heartbeat w/ or w/o tachy
Anxiety or fear of impending death
Abdominal or chest pain
Symptoms between paroxysm:
cold hands and feet
What are paroxysms of pheochromocytoma and how do you stop them?
They are extreme explosion of catecholamines into the circulatory system caused by movement of the adrenal gland and tumor
--> stopped by catecholamines:
Reuptake into the tumor
Taken up into target cell
Metabolized (catecholamine-N-methyl transferase)
What are causes of death in patients with unsuspected pheochromocytomas?
Dissection aortic aneurysm