Lecture 6-Adrenal Glands Flashcards
Summarize adrenal gland form and function
Z. Glomerulosa= releases aldosterone, zone regulated by AGII, K+
Z. fasciculata= releases cortisol and androgens regulated by ACTH
Z. Reticularis=releases cortisol and androgens regulated by ACTH
Medulla= epinephrine and Norepinephrine—> sympathetic control
Summarize distribution blood supply of adrenal glands
Superior, middle, and inferior suprarenal arteries supply the adrenal gland. Venous drainage to IVC and renal vein.
• Arteries form plexus & perfuse the gland from periphery to the center.
• Medulla receives dual blood supply enriched with hormones.
What is the role of CRH & ACTH in the hypothalamic-pituitary-adrenal axis ?
Paraventricular nucleus neurons secrete CRH, which targets corticotropes.
Corticotropes secrete ACTH, which targets the adrenal cortex
What are the negative feedback of the hypothalamic-pituitary-adrenal axis?
CNS experiences biochemical, psychological, and physical stress+ circadian rhythms stimulate hypothalamus releases CRH
Anterior pituitary secretes ACTH
ACTH stimulates adrenal cortex to secrete cortisol
Cortisol inhibits anterior pituitary + hypothalamus
ACTH inhibits hypothalamus
What is the stress and role of cortisol?
• Any type of physical or mental stress can lead within minutes to greatly enhanced secretion of ACTH and consequently cortisol.
• Cortisol is essential to deal with the various physical & mental stresses of life. – Intense heat or cold – Minor or debilitating illnesses – Infections – Trauma / surgery – Fasting / starvation
What is the mechanism of action of CRH to promote ACTH synthesis?
CRH binds receptor to increase cAMP
cAMP dependent PKA causes increased Ca2+ influx
Fusion of ACTH containing vesicles , leading to exocytosis of ACTH
Corticotroph cell in anterior pituitary
What is ACTH?
• ACTH is secreted as a large preprohormone
“Proopiomelanocortin”
- ACTH is the main physiologic product:
- a MSH is contained in the sequence of ACTH
- In physiologic range MSH is not significant
- Excess ACTH secretion results in hyper pigmentation
What is StAR?
Steriodogenic active regulatory protein
What is the short term and long term role of ACTH mechanism of action?
• Short-term role: ↑Conversion of cholesterol to pregnenolone
• Long-term role: ↑number of LDL receptors and ↑synthesis of mRNAs
leading to enzymes
How is aldosterone regulated?
Renin-angiotensin system (major)
Hypothalamic-ACTH loop(minor)
Angiotensin II K+ increase + ACTH stimulates Adrenal Cortex (Z. Glomerulosa) to stimulate aldosterone
What is the regulation of aldosterone-Angiotensin II -Z. Glomerulosa?
Ang II binds to receptor (decreased blood vol.)
Leading to increased DAG + IP3 leading to Ca2+—> stimulation of aldosterone synthesis
increased DAG + IP3 leads to activation of PKC and stimulation of aldosterone synthesis
Aldosterone —> increase renal Na+ resorption (restore blood vol.)
What is the role of aldosterone- K+-Zona glomerulosa?
Hyperkalemia (K+)—> depolarization causing increased Ca2+ and activation of aldosterone synthesis
Aldosterone leads to increased renal K+ secretion and restore serum [K+]
Why do we need aldosterone?
Maintain blood volume
•Stimulates K+ excretion into urine •Stimulates Na+ resorption into blood
– Via kidneys (less regulatory - saliva, sweat & GIT)
– Water follows sodium ions causing an increase in blood volume that will raise the blood pressure.
Regulate H+ secretion
• Renalsecretion–(detailsinlaterslides)
Explain in detail aldosterone regulation -renin angiotensin & aldosterone
- Decrease in Na+ concentration, decrease in ECF volume
- Kidney JGA releases renin
- Aniotensinogen reacts with renin to form angiotensin I
- Angiotensin reacts with converting enzymes in lungs to form angiotensin II
- AGII stimulates adrenal cortex to release aldosterone
- Aldosterone reacts with kidney DCT to reabsorb Na+ retain water and excrete K+
- Increase in Na+ concentration. Increase in ECF volume.
- This inhibits kidney JGA from releasing renin
What is hyper aldosterone?
Cause: Increased secretion of aldosterone from adrenal cortex. Symptoms: Hypertension, dec K+, metabolic alkalosis. (No edema due to
aldosterone escape mechanism…”backflow”.)
Differentiate primary (Conn’s syndrome) and secondary hyper aldosteronism
Primary (Conn’s syndrome)- Adrenal adenoma (tumor) or idiopathic hyperplasia of zona glomerulosa. (Increased aldosterone, decreased renin)
Secondary- Reno-vascular hypertension (renal artery stenosis), juxtaglomerular cell tumor- (activation of RAAS). (Increased aldosterone, increased renin)
Explain the primary hyperaldosteronism symptoms
•Hypertension: K+ exchange for Na+
– ↑ Na+ & H2O resorption from tubulesinc. ECF
– Hypertension/inc. BP leads to increased ECF volume
•Hypokalemia: K+ secreted into urine
– hypokalemia causing muscle weakness & arrhythmias.
- Alkalosis: H+ influx instead of K+ as a result of lost K+ in urine and present hypokalemia.
- Dec. renin (1o): increased BP—>inhibited secretion.
Give the lab analysis of primary aldosteronism
↑Aldosterone ↑Sodium(hypertension) ↓Potassium
↓Renin
Metabolic Alkalosis
Give the lab analysis of secondary hyperaldosteronism
↑Aldosterone ↑Sodium(hypertension) ↓Potassium
↑Renin
Metabolic Alkalosis
What are the triggers of the Catecholamines release?
Stress
Increased exercise
Exposure to cold
Hypoglycemia
Outline the mechanism of ACh in the adrenal medulla
ACh stimulates nicotine receptors
Sodium influx into the chromaffin cell—> depolarization of chromaffin cell —> Ca2+ influx—> fusion of vesicles—> release of epinephrine and norepinephrine
What are the functions of Catecholamines?
Epi/NE:
-Adipose tissue increased lipolysis—> free fatty acids+ glycerol is used for glycogenolysis in liver
-glycogenolysis on skeletal and liver increased
Glycogenolysis in liver, allows glucose to be used for energy for fight or flight
Whaat are the physiological effects of stress?
Stress-hypothalamus stimulates pituitary-adrenal cortex to release mineral corticoids to increase blood pressure for long term purposes
Pituitary adrenal cortex releases glucocorticoids to stimulate protein breakdown , fat lipolysis, and immune suppression for both long and short term responses
Hypothalamus stimulates ANS/Adrenal medulla to release Catecholamines
This increasss HR & BP blood glucose, metabolic rate, bronchodilation for a short term basis
How is Addison treated?
Replacement of glucocorticoids and mineralcorticoids
Whaat are the clinical features of Addison’s?
Hypoglycemia Anorexia, weight loss, nausea, vomitting Weakness Hypotension Hyperkalemia Metabolic acidosis Decreased pubic and axillary hair fin females Hyperpigmentation
ACTH levels increased( negative feedback effect of decreased cortisol)
What is the treatment of Conn syndrome (aldosterone-secreting tumor)?
Aldosterone antagonist (e.g. spironolactone) surgery
What are the clinical features of Conn syndrome?
Hypertension
Hypokalemia
Metabolic alkalosis
Decreased renin levels
