Adrenal gland Flashcards by Heo Mun Ho

Location of adrenal glands + peritonisation

Superior pole of kidneys

Retroperitoneal

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Outline diagrammatically the structure of the (compound) adrenal gland, indicating its zonation.

Capsule

Zona glomerulosa
Zona fasiculata
Zona reticularis

adrenal medulla

Zona reticularis
Zona fasiculata
Zona glomerulosa

Capsule

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Adrenal gland is split into 2 parts

Adrenal medulla (25%)
Adrenal cortex (75%)

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Which part of the adrenal gland is the true endocrine gland

Adrenal cortex

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Adrenal medulla (centre part of adrenal gland) isn’t actually a true endocrine gland, what is its tissue derived from

Neural crest tissue

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The adrenal cortex (75% of adrenal gland) secretes 3 classes of steroid hormones- name them

Mineralocorticoids, e.g. aldosterone

Glucocorticoids, e.g. cortisol

Sex steroids

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What class of hormones does aldosterone belong to + function

mineralocorticoids

regulates Na+ and K+

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What class of hormones does cortisol belong to + function

Glucocorticoids

Maintains plasma glucose

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Adrenal medulla secretes what class of hormones

Catecholamines, e.g. epinephrine (adrenaline), noradrenaline, dopamine

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The adrenal cortex is arranged in 3 concentric zones/layers, each layer producing a different class of hormone - name the layers and the hormone type secreted by each

Zona glomerulosa - aldosterone (mineralocorticoid)

Zona fasiculata - glucocorticoids

Zona reticularis - sex steroids

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Which zone of the adrenal cortex is most superficial

Which zone is the thickest

Zona glomerulosa - most superficial

Zona fasiculata - thickest

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What are all steroid hormones derived from + how are different steroid hormones derived from the same origin

All steroid hormones are derived from cholesterol, but different enzymes found in the different adrenal zones result in different end products of cholesterol

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Outline the basic pathway that produces
-mineralocorticoids (e.g. aldosterone)

from cholesterol

+ what key enzyme is involved

Cholesterol –> intermediate compound –> progesterone, converted by 21-HYDROXYLASE, into another intermediate compound –> aldosterone

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What enzyme is not involved in the production of sex steroids from cholesterol but is required in the production of mineralocorticoids and glucocorticoids from cholesterol

21-hydroxylase

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Andro-stenedione and testosterone can be converted by what enzyme into forms of oestrogen such as oestrone and oestradiol

(naturally occurring forms of estrogen in females are estrone, estradiol and estriol)

aromatase

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Defects in the enzyme, 21-hydroxylase, is a common cause of what condition + what does this condition result in

congenital adrenal hyperplasia
- resulting in deficiency of aldosterone and cortisol so disruption of salt and glucose balance as 21-hydroxylase is required for production of these

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Androgens (male sex hormones such as testosterone) are precursors of what

Oestrogens

-androgens are produced in both sexes however just more abundant in males

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Ambiguous genitalia is a sign of congenital adrenal hyperplasia (CAH) - why is this

Since CAH is when you’re deficient in 21-hydroxylase, mineralocorticoid and glucocorticoid production is limited so accumulating steroid precursors are channelled into excessive adrenal androgen production which doesn’t require 21-hydroxylase

Points of control in the hypothalamic-pituitary-adrenal pathway of cortisol

Cortisol exhibits long loop negative feedback

on ACTH in the AP
on CRH in the hypothalamus

ACTH also exhibits short loop negative feedback on CRH in hypothalamus

Why does a deficit in 21-hydroxylase cause hyperplasia of the adrenal gland, i.e. why does it get bigger (3)

Lack of 21-hydroxylase inhibits synthesis of cortisol.

This removes the negative feedback on ACTH and CRH release.

Increased ACTH secretion excessively stimulates adrenal gland –> enlargement of adrenal glands

How is cortisol transported in the blood

95% is bound to carrier protein, cortisol binding globulin

only unbound hormone can diffuse into target cells

How does cortisol stimulate altered gene expression

As it’s a steroid hormone, it binds to cytoplasmic receptor

The hormone receptor complex migrates to the nucleus, binding to DNA to alter gene expression, transcription and translation

Describe the normal circadian basal rhythm in plasma total cortisol concentration (3)

Burst of cortisol release every morning around 7am, preceded (i.e. before) by a burst of ACTH release (highest during morning because of physiological stress)

Plasma cortisol starts decreasing after about 9am then release fluctuates throughout the day depending on the stimuli

Decreases further towards midnight and stays low until the morning burst

Why does cortisol persist in the blood longer than ACTH (adrenocorticotropic hormone)

Because cortisol is a steroid hormone so has a longer half life than ACTH (a peptide hormone)

Justify the view that the adrenal cortex is essential for survival of the individual while the adrenal medulla is not.

Adrenal cortex produces cortisol - loss of cortisol means we can't deal with physiological stress, particularly in terms of maintaining BG levels. - Cortisol is crucial in helping to protect the brain from hypoglycaemia; it has a permissive action on glucagon, which is vital as glucagon alone is inadequate in responding to a hypoglycaemic challenge

Physiological stress v psychological stress

physiological - maintaining plasma glucose, BP etc psychological - mental stress

Overall function of cortisol (a glucocorticoid)

Influences glucose metabolism

Cortisol has glucocorticoid AND non-glucocorticoid actions | - describe the non-glucocorticoid actions of cortisol (i.e. those that don't influence glucose metabolism) (4)

1. Decreases Ca2+ absorption from gut and increases its excretion in urine --> net Ca2+ loss 2. Impairs mood + cognition - associated with hypercortisolaemia 3. Permissive with noradrenaline, particularly in vasoconstriction 4. Suppresses the immune system - cortisol reduces circulating lymphocytes, antibody formation and inhibits inflammation

Effect on plasma glucose concentration of administering cortisol to a normal subject; and list the TARGET SITES and processes of cortisol underlying that effect (i.e. describe the glucocorticoid actions (those that influence glucose metabolism) of cortisol) (4)

Increases plasma glucose - by acting on liver, muscle, adipose tissue 1. Stimulates gluconeogenesis - cortisol acts on LIVER TISSUE and stimulates formation of glucose from amino acids 2. Stimulates proteolysis - cortisol acts on MUSCLE TISSUE and stimulates breakdown of muscle to provide gluconeogenic substrates 3. Stimulates lipolysis - cortisol acts on ADIPOSE TISSUE and stimulates adipose tissue breakdown which increases free fatty acids creating an alternative energy source and also a gluconeogenic substrate 4. Decrease insulin sensitivity

Side effects of glucocorticoid therapy (3)

Muscle wasting - as cortisol stimulates protein breakdown Loss of percutaneous fat - as cortisol stimulates lipolysis so get thinking of skin Increased susceptibility to infection as immune function suppressed

Function of aldosterone + effect of increased aldosterone

MAINTAINS BP - increases the reabsorption of Na+ ions (and therefore H2O) and promotes the excretion of K+ ions increased aldosterone --> increased blood volume and BP

Where does aldosterone act on

distal tubule of the kidney

Hypersecretion of cortisol causes (i.e. hyperfunction of adrenal cortex) (3)

Cushing's syndrome Cushing's disease Iatrogenic - too much cortisol administered

Cushing's syndrome involves hypersecretion of what Cushing's syndrome aka

of cortisol, commonly due to a tumour in the adrenal cortex Primary hypercortisolism

Cushing's disease involves hypersecretion of what Cushing's disease aka

of cortisol, commonly due to a tumour in the pituitary gland Secondary hypercortisolism - excess ACTH

What disease is associated with adrenal hypofunction + describe it

Addison's disease | -hyposecretion of all adrenal steroid hormones (not just cortisol) due to autoimmune destruction of adrenal cortex

What's special about post-ganglionic fibres in the adrenal medulla

They have no axons, so just release their neurohormones (adrenaline) into blood

What is a pheochromocytoma + where is it found + what effect does it have

rare neuroendocrine tumour, found in adrenal medulla which results in excess catecholamines (adrenaline etc) --> increased HR --> increased CO --> increased BP Is diabetogenic (i.e. causes DM like symptoms)

Tertiary hypercortisolaemia would be due to a pathology where

Hypothalamus

Why do we need to be careful when withdrawing chronic glucocorticoid treatment

Exogenous cortisol enhances negative feedback effects of cortisol on the hypothalamus and pituitary releasing CRH and ACTH respectively So withdrawing it decreased the negative feedback effects,?

Precursor of adrenaline and noradrenaline

Dopamine

Schematics of a normal hypothalamic-pituitary-adrenal axis + negative feedback

``` CRH | | ACTH | | Cortisol ``` Cortisol production from adrenal gland will exhibit negative feedback on ACTH and CRH

Precursors of the sex steroids (2)

DHEA (dehydroepiandrosterone) Andro-stenedione Ultimately from cholesterol

Progesterone is a precursor of... (2)

mineralocorticoids (aldosterone) glucocorticoids (cortisol)