O'Driscoll: Adrenal Gland Flashcards by Megan Foggia

Adrenal glands contribute significantly to maintaining homeostasis through their roles in regulation of the body’s adaptive response to (blank), maintenance of body (blank x3), and control of (blank)

stress
water, Na+, K+
blood pressure

How well did you know this?

Not at all

Perfectly

Main hormones produced by the adrenal glands belong to 2 different families. What are they?

Steroid hormones: glucocorticoids, mineralocorticoids, and androgens
Catecholamines: norepinephrine and epinephrine

How well did you know this?

Not at all

Perfectly

90% of the adrenal gland is the outer adrenal (blank); 10% is the inner adrenal (blank)

cortex; medulla

How well did you know this?

Not at all

Perfectly

The adrenal glands are required for life. Complete adrenal insufficiency can lead to lead within 2 weeks. What two things can cause death?

circulatory collapse (shock) 
hypoglycemic coma

How well did you know this?

Not at all

Perfectly

4 functional zones of the adrenal glands

zona glomerulosa
zona fasciculata
zona reticularis
medulla

How well did you know this?

Not at all

Perfectly

Which zone produces MINERALOCORTICOIDS and is controlled by ECF conc of angiotensin II and K+, as well as the kidney?

zona glomerulosa

How well did you know this?

Not at all

Perfectly

Which zone produces GLUCOCORTICOIDS and is controlled by the hypothalamic-pituitary axis via ACTH?

zona fasciculata

How well did you know this?

Not at all

Perfectly

Which zone produces ANDROGENS and is controlled by hypothalamic-pituitary axis via ACTH?

zona reticularis

How well did you know this?

Not at all

Perfectly

Which zone produces CATECHOLAMINES and is controlled by the sympathetic nervous system?

medulla

How well did you know this?

Not at all

Perfectly

Chief secretory product of the glomerulosa?

The fasciculata? The reticularis?

aldosterone; cortisol; sex hormones and DHEA

How well did you know this?

Not at all

Perfectly

Very potent - ~90% of all mineralocorticoid activity

aldosterone

How well did you know this?

Not at all

Perfectly

Some adrenocortical hormones have both mineralocorticoid and glucocorticoid activites. This hormone is very potent- ~95% of all glucocorticoid activity. Slight mineralocorticoid activity but large quantity secreted.

cortisol

How well did you know this?

Not at all

Perfectly

Adrenocortical hormones are transported in blood bount to (blank) and (blank)

corticosteroid binding globulin (CBG); albumin

How well did you know this?

Not at all

Perfectly

90-95% bound
T1/2 = 60-90 mins
[blood] = 12microg/dL

cortisol

How well did you know this?

Not at all

Perfectly

60% bound
T1/2 = 20mins
[blood] = 6microg/dL

aldosterone

How well did you know this?

Not at all

Perfectly

What mineralocorticoid does this:
increases sodium retention
increases K+ excression
targets the kidney (principal cells in distal tubule and collecting duct, and intercalated cells in the collecting duct)

aldosterone

How well did you know this?

Not at all

Perfectly

Mineralocorticoids elicit effects by producing changes in (blank). Effects are not (blank) - require 45-60 min for proteins to be synthesized

gene transcription; immediate

How well did you know this?

Not at all

Perfectly

Aldosterone has genomic and non-genomic effects. What are its genomic effects? Non-genomic?

increased transcription of genes involved in ion transport: reabsorption of Na+, loss of K+
activation of second messenger system: H+/bicarb exchange

How well did you know this?

Not at all

Perfectly

Aldosterone increases renal tubular absorption of (blank) and secretion of (blank). What occurs with a total lack of aldosterone secretion? What is aldosterone a key mediator of?

Na+; K+
transient loss of Na+ in the urine
blood pressure

How well did you know this?

Not at all

Perfectly

Excess Aldosterone causes an increase in ECF Volume and Arterial Pressure but has Only a Small Effect on Plasma Na+ concentration. Why?

Na+ reabsorbed and water follows. So there is little change in CONCENTRATION. ECF volume increases almost as much as the retained Na+ but without much change in Na+ concentration.

How well did you know this?

Not at all

Perfectly

When aldosterone has its effect and increases arterial pressure, what is the compensatory mechanism that maintains blood pressure within normal range?

Increased distal tubule Na+ delivery, so increased kidney excretion of both sodium and water – aldosterone escape

How well did you know this?

Not at all

Perfectly

What happens to Na+ when aldosterone secretion becomes zero?

Large amounts of Na+ lost in the urine
Decreases ECF volume
Severe dehydration, low blood volume
CIRCULATORY SHOCK!!!

How well did you know this?

Not at all

Perfectly

What happens when there is excess aldosterone?

Loss of K+ in urine, so K+ is transported from ECF into cells. HYPOKALEMIA and muscle weakness and cramping ensue. Increased secretion of H+ in exchange for Na+ in the intercalated cells of the collecting tubules can result in METABOLIC ALKALOSIS.

How well did you know this?

Not at all

Perfectly

What happens when there is too little aldosterone?

ECF K+ rises way too high. HYPERKALEMIA, which can cause cardiac toxicity.

How well did you know this?

Not at all

Perfectly

(blank) is much less potent than aldosterone, but has a [plasma] that is 2000 times greater. Cortisol can bind to mineralocorticoid receptors with (blank) affinity, but cortisone DOES NOT.

cortisol; high

Renal epithelial cells contain 11β-hydroxysteroid dehydrogenase type 2. What does this do?

converts cortisol to cortisone

Genetic deficiency of 11β-hydroxysteroid dehydrogenase type 2 activity Can also be caused by ingestion of large amounts of licorice

AME: apparent mineralocorticoid excess syndrome

AME patient has similar symptoms as a patient with excess aldosterone secretion, except for one thing...

plasma aldosterone levels are low

Aldosterone secretion is primarily regulated in these two ways

1. decreased blood volume or blood pressure | 2. increased K+ in blood

(blank) appears to play a “permissive role” in the regulation of aldosterone secretion. If there is even a small amount of it secreted by the anterior pituitary it is usually enough to permit the adrenal glands to secrete whatever amount of aldosterone is required. However, total absence of it can significantly reduce aldosterone secretion.

ACTH

Discuss how plasma volume is regulated by the renin-angiotensin-aldosterone system

``` decreased plasma volume increased angiotensin II increased aldosterone increased vasoconstriction increased reabsorption of Na+ in distal tubule increased plasma volume ```

Cortisol is a very potent (blank). It makes up 95% of (blank). What is its hallmark effect?!

glucocorticoid; glucocorticoids; increase blood glucose

Main function of cortisol? | What is its target? What cells express glucocorticoid receptors?

Effects metabolism of carbs, proteins, fats | Important in resisting stress and inflammation; virtually every tissue; most cells express these receptors

Cortisol has a cellular mechanism of action. It binds to the cytoplasmic glucocorticoid receptor, forms a hormone-receptor complex with specific regulatory DNA sequences called (blank) and induces or represses gene trx. High [glucocorticoid] can also have more rapid nongenomic effects.

glucocorticoid response elements

Carb metabolism: Cortisol stimulates (blank) and decreases (blank) utilization by cells, which increases storage of (blank) as glycogen in liver cells. Cortisol increased (blank) concentration, which in turn stimulates secretion of (blank). Excess secretion of glucocorticoids can lead to what?

gluconeogeneis; glucose; glucose; blood glucose; insulin; hyperglycemia

Protein metabolism: Cortisol mobilizes (blank) from the nonhepatic tissues, diminishes the tissue stores of (blank) and at the same time it increases the (blank) required for the hepatic effects

amino acids; protein; liver enzymes

Fat metabolism: Cortisol increases use/oxidation of (blank) from adipose tissue for metabolic energy. This is an important factor for long-term conservation of body (blank) and (blank)

fatty acids; glucose; glycogen

Principal effects of cortisol: preservation of (blank) reserves and increased mobilization of high energy fuels, like (blank) and (blank)

carbohydrate; protein; fat

Why is it beneficial that glucocorticoid secretion increases in stressful situations? Cortisol also has (blank) effects.

Rapid mobilization of amino acids and fats makes them available for energy and synthesis of other compounds needed for maintenance anti-inflammatory

Five main stages of inflammation

1. damaged tissue cells release chemical substances 2. increase in blood flow to inflamed area 3. increased capillary permeability 4. infiltration of the area by leukocytes 5. ingrowth of fibrous tissue

High levels of cortisol have two basic anti-inflammatory effects

1. can block the early stages of the inflammation process before inflammation begins 2. if inflammation has begun, it causes rapid resolution of the inflammation and increased rapidity of healing

High levels of cortisol stabilize (blank) membranes, decrease the permeability of (blank), decrease migration of (blank), decrease phagocytosis, suppress the (blank), and decrease fever.

lysosomal; capillaries; white blood cells; immune system

Cortisol has therapeutic utility in these three realms

allergies autoimmune diseases transplantation

What is cortisol's effect on blood cells and on immunity in infectious diseases? So what can hypercortisolemia cause?

decreases blood eosinophils and lymphocytes; lymphocytopenia and eosinopenia

Cortisol also increases the production of RBCs. If there is too much cortisol, what does this lead to? If there is no cortisol secretion, what does this lead to?

polycythemia; anemia

What effect do glucocorticoids have on the CNS?

decreased CRH

What effect do glucocorticoids have on the liver?

increased gluconeogenesis

What effect do glucocorticoids have on the pituitary?

decreased ACTH secretion and synthesis

What effect do glucocorticoids have on muscle?

Increased protein catabolism, decreased glucose utilization, decreased insulin sensitivity, decreased protein synthesis

What effect do glucocorticoids have on the immune system?

Decreased conc of eosinophils, basophils, and lymphocytes | Decreased cellular immunity

Cortisol secretion is regulated by (blank) secretion from the anterior pituitary. What controls secretion at the level of the hypothalamus?

ACTH; ACTH secretion controlled by CRF (corticotropin releasing factor) from the hypothalamus

Cortisol has negative feedback effects on the hypothalamus to decrease formation of (blank) and on the anterior pituitary to decrease formation of (blank). This decreases plasma cortisol levels at times when the body is not stressed.

CRF; ACTH

Release of CRH, ACTH, and cortisol is high in the (blank) but low in the (blank). Release is (blank).

early morning; evening; pulsatile

adrenal androgen

DHEA

Failure of the adrenal cortices to produce sufficient adrenocortical hormones

hypoadrenalism - adrenal insufficiency

Causes: destruction of the adrenal cortex by - Autoimmunity (80%) antibodies that react with several steroidogenic enzymes (most often 21-hydroxylase) - Tuberculosis - fungal infections - adrenal hemorrhage

Primary adrenal insufficiency (Addison's disease)

Much more common Causes: Pituitary gland fails to produce sufficient ACTH. If ACTH output is too low, cortisol production drops. Eventually, the adrenal glands can shrink due to lack of ACTH stimulation

Secondary adrenal insufficiency

With Addison's disease, there can be a mineralocorticoid deficiency leading to (blank), a glucocorticoid deficiency leading to (blank x3), or pigmentation due to increased (blank) production

circulatory shock weight loss, weakness, extreme sensitivity to stress melanin

ACTH is derived from the POMC gene. When the rate of secretion of ACTH is high, increases formation of some of the other (blank)

POMC-derived hormones, like MSH

Causes: a critical deficiency of mineralocorticoids and glucocorticoids, that generally follows acute stress, sepsis, trauma, surgery, or omission of steroid therapy in patients who have Addison’s

Addisonian crisis

Describes the signs and symptoms associated with prolonged exposure to inappropriately high levels of the hormone cortisol (excess secretion of androgens may also cause important effects)

Cushing's syndrome (hyperadrenalism)

Hypersecretion of CRH or ACTH (Cushing's disease) Adrenal cortex adenomas Ectopic secretion of ACTH Hypercortisolism

Causes of cushing's syndrome or hyperadrenalism

Symptoms of Cushing's syndrome due to glucocorticoid excess

increased gluconeogenesis, hyperglycemia buffalo torso moon face weakness, osteoporosis, strige on skin

Symptoms of Cushing's syndrome due to androgen excess

acne, hirsutism (excess facial hair)

High cortisol leads to a peculiar type of obesity with excess fat being deposited in chest and head regions giving rise to these two symptoms

buffalo torso | moon face

Causes: small tumor of the zona glomerulosa cells that secretes large amounts of aldosterone hyperplastic adrenal cortices secrete aldosterone rather than cortisol

Conn's syndrome - Primary aldosteronism

What can mineralocorticoid excess lead to in Conn's syndrome?

hypokalemia--> muscle paralysis hypervolemia-->hypertension low plasma renin

Adrenocortical tumor secreting excessive quantities of androgens

adrenogenital syndrome

What can androgen excess cause in females? In males?

masculinization; rapid development of male sexual organs

Cause: Autosomal recessive disorder – enzyme inefficiencies commonly leading to deficient production of cortisol and aldosterone together with excessive production of sex steroids 95% of cases due to 21 hydroxylase deficiency

congenital adrenal hyperplasia

In response to sympathetic neuronal stimulation & the resulting release of acetylcholine → stimulates the production and release of catecholamines

adrenal medulla

Principal cell type of adrenal medulla; modified postganglionic neurons

chromaffin cells

Secretory products of the adrenal medulla

epinephrine: norepi (4:1)

The adrenals are the sole source of (blank)

epinephrine

T/F: The adrenal medulla is not essential for life as long as the sympathetic nervous system is intact

True!

The medulla is richly innervated by preganglionic sympathetic fibers and is in essence, an extension of the (blank) nervous system

sympathetic

Catecholamines are synthesized in (blank) and stored in electron dense (blank)

chromaffin cells; chromaffin granules

What are catecholamines (dopamine-->norepi->epi) derived from? How many enzymatic reactions does it take to go from tyrosine to epinephrine?

tyrosine; 4 rxns

Following secretion into the blood, most catecholamines circulate bound to (blank) with low affinity. What is the T1/2 of catecholamines?

albumin; VERY SHORT

What is the major end product of epi and norepi metabolism?

vanillylmandelic acid

What is the main function of the adrenal medullary hormones? In the longer term, actions are supported by glucocorticoids.

to make rapid, short-term adjustments to changes in the external or internal environment (fight or flight)

What is the mechanism of action of catecholamines?

physiological effects mediated by binding to cell membrane G protein–coupled adrenergic receptors distributed widely throughout the body

Chromaffin cell tumor that causes over secretion of catecholamines; elevated heart rate, hypertension, anxiety, sweating, hyperglycemis

pheochromocytoma