70 - Adrenocortical Function and Dysfunction Flashcards by Jack Cuthbertson

Relationship between adrenal cortex and medulla

Two endocrine glands of different embryological origin that fuse during development

How well did you know this?

Not at all

Perfectly

Basic aspects of adrenal medulla

Modified sympathetic ganglion, secretes catecholamines (neurohormones)

How well did you know this?

Not at all

Perfectly

Basic aspects of adrenal cortex

True endocrine gland.
Secretes steroids (classical hormones)

How well did you know this?

Not at all

Perfectly

Regions of adrenal cortex
1
2
3

Zona reticularis (sex hormones)
Zona fasciculata (glucocorticoids)
Zona glormerulosa (aldosterone)

How well did you know this?

Not at all

Perfectly

Hormones produced by zona reticularis

Sex hormones (ndrogens, oestrogens, dehydroepiangeosterone)

How well did you know this?

Not at all

Perfectly

Hormones produced by zona fasciculata

Glucocorticoids (cortisol)

How well did you know this?

Not at all

Perfectly

Zones of adrenal cortex that produce hormones together

Zona reticularis and fasciculata (reticularis makes more sex hormones, fasciculata makes more glucocotricoids)

How well did you know this?

Not at all

Perfectly

Hormones produced exclusively be zona glomerulosa

Mineralocorticoids (aldosterone)

How well did you know this?

Not at all

Perfectly

Progenitor for aldosterone, cortisol and sex hormones

Progesterone

How well did you know this?

Not at all

Perfectly

Active form of testosterone

Dihydro-testosterone

How well did you know this?

Not at all

Perfectly

Two pathways to sex hormone formation

Can derive from progesterone or DHEA (dehydroepiangeosterone)

How well did you know this?

Not at all

Perfectly

How are different steroids derived from cholesterol in the adrenal cortex?

Cells produce different steroids because they contain different enzymes

How well did you know this?

Not at all

Perfectly

Pathway for control of cortisol secretion
1
2
3
4

1) Hypothalamus releases corticotrophin releasing hormone into portal system.
2) Anterior pituitary releases adrenocorticotrophic hormone
3) Adrenal cortex releases cortisol.
4) Cortisol negatively feeds back on ACTH and CRH release (long loop negative feedback)

How well did you know this?

Not at all

Perfectly

Roles of cortisol
1
2
3
4
5
6
7

1) Promotes gluconeogenesis in liver
2) Causes breakdown of skeletal muscle proteins
– Substrate for gluconeogenesis
3) Enhances lipolysis – FA for energy
4) Suppresses the immune system
5) Causes negative calcium balance
– decreases absorption, increases excretion, increases bone breakdown
6) Influences brain function –mood, memory, learning
7) Adaptation to stress

How well did you know this?

Not at all

Perfectly

Main higher brain functions involved in regulating cortisol release

Circadian rhythm and stress

How well did you know this?

Not at all

Perfectly

Roles of CRH and ACTH, other than releasing cortisol
1
2
3
4

• CRH and ACTH have some stress‐related
functions in the immune and nervous systems

• The CRH family includes several peptides

– CRH mediates several functions
• Effects on inflammation and immune responses
• Inhibition of appetite
• Signals the onset of labor
• Appears linked to several mood disorders

– Urocortin: brain neuropeptide that decreases appetite

How well did you know this?

Not at all

Perfectly

Roles of CRH family
1
2
3
4
5

– CRH mediates several functions
• Effects on inflammation and immune responses
• Inhibition of appetite
• Signals the onset of labor
• Appears linked to several mood disorders

– Urocortin: brain neuropeptide that decreases appetite

Roles of ACTH, other than cortisol regulation
1
2
3

• POMC (pro‐opiomelanocortin) is a large protein
thata yields several bioactive peptides by proteolysis

• ACTH and beta‐endorphin (blocks pain perception) are among the peptides produced in the anterior pituitary from POMC

• Outside the pituitary processing creates alpha‐MSH
– melanocyte‐stimulating hormone: decreasess food intake & increases skin melanin

Significance of ACTH derivation from POMC

The more the anterior pituitary is stimulated to release ACTH, more POMC needs to be cleaved to form ACTH, which will form other bioactive fragments of POMC.

Melanocortins
1
2

– Family name for the MSH hormones and ACTH
– The effects of the peptides depend on which
melanocortin receptor subtypes are stimulated

Broad roles of cortisol
1
2
3
4

• Essential for life
• Helps body cope with long‐term stress
• Protects against hypoglycemia by stimulating
catabolism of energy stores
• Permissive for glucagon & catecholamine
actions

Diurnal rhythm of cortisol

Peaks in the morning, lowest at night

Therapeutic roles of cortisol
1
2
3
4

• Suppresses the immune system
• Inhibits the inflammatory response
• Some specific uses
– Bee stings, poison ivy, and pollen allergies
– Prevents rejection of transplanted organs
• Long‐term use results in inhibition of ACTH
secretion and atrophy of cortisol‐secreting cells
– Taper doses gradually when stopping cortisol therapy

Half life of cortisol

60 - 90 minutes

Hypersecretion disorders of the adrenal cortex 1 2 3

1) Hyperaldosteronism 2) Cushing's syndrome 3) Adrenogenital syndrome (excess androgens and oestrogen)

Hyperaldosteronism effects 1 2 3

– Primary hyperaldosteronism (Conn’s syndrome) – Secondary hyperaldosteronism (RAS) • Both cause hypernatremia, hypokalemia, hypertension

``` Cushing's syndrome effects 1 2 3 4 ```

– Primary adrenal cortex tumors that autonomously secretes cortisol – Secondary pituitary tumor that autonomously secretes ACTH (Cushing’s disease) – Hyperstimulation (CRH, ACTH) – Iatrogenic (physician-caused) hypercortisolism – treat with cortisol therapy • All cause glucose excess, protein shortage, abnormal fat distribution

``` Androgenital syndrome effects 1 2 3 4 ```

Excess androgens and oestrogen – Lack enzyme in cortisol steroidogenic pathway – Inappropriate masculinisation in all but adult males – Treat with glucorticoids – Repairs glucorticoid deficit and inhibits ACTH (reducing steroid secretion)

``` Symptoms of Cushing's syndromes 1 2 3 a, b 4 a 5 6 ```

– Excess gluconeogenesis causes hyperglycemia mimics diabetes – Muscle protein breakdown, lipolysis causes wasting – Paradoxical fat deposits in trunk & face due to increased appetite a) Thin arms & legs, trunk obesity, “moon face” b) Stretched skin due to fat depots causes reddish purple striae – Mineralocortocoid action of excess glucocorticoid (because of similar structure) a) Salt & water retention, “moon face”, weakness, hypertension – Osteoporosis – Mood elevation then depression, difficult learning & memory

Hormone profile of secondary Cushing's from hypothalamic hypersecretion

High CRH High ACTH High cortisol

Hormone profile of secondary Cushing's from anteroir pituitary hypersecretion

Low CRH High ACTH High cortisol

Hormone profile of primary Cushing's

Low CRH Low ACTH High cortisol

Most common primary adrenal cortex disorder of hyposecretion

Addison's disease

``` Addison's disaese 1 2 3 a, b 4 a ```

Primary adrenal insufficiency Addison’s Disease – Autoimmune destruction of adrenal cortex – Hyposecretion of all adrenal steroid hormones – Decreased Aldosterone a) K+ retention → Cardiac arrhythmias b) Na+ depletion → hypotension – Decreased Cortisol a) Decreased stress response & hypoglycaemia

Are hypersecreting or hyposecreting adrenal cortex defects more common?

Hypersecreting are more common

Adrenal cortex hyposecreting defects 1 2

1) Addison's disease | 2) Adrenal steroid enzyme defects

Effect of adrenal steroid enzyme defects

Lack of cortisol & aldersterone causes increased androgens & adrenogenital syndrome

Catecholamines produced in adrenal medulla 1 2 3

1) Epinephrine (only made in adrenal medulla) 2) Norepinephrine 3) Dopamine

Chromaffin cells

Modified postganglionic sympathetic neurons that release epinephrine. Synapsed onto by preganglionic sympathetic neurons from the spinal cord.

``` Adrenomedullary hormone effects 1 2 3 4 ```

``` • Fight‐or‐flight responses – Increased cardiac rate and contractility, increased TPR, increased BP • Metabolic effects – Increased glucose & FFA, increased BMR • Central Effects – Increased arousal & alertness • Stress Responses – Physical – Psychological ```

Hyposecretion disorders of the adrenal medulla

None recognised

``` Hypersecretion disorders of adrenal medulla 1 2 3 4 ```

– Pheochromocytomas (tumor) – Rare – Potentially deadly (hypertension) – Treatment: removal