Adrenal Glands + Steroid hormones

Outline the gross anatomy of the adrenal glands. (4)

1. Superior to kidneys in renal fascia and posterior to diaphragm.

2. Right gland is post. to - liver and IVC.

3. Left gland is post. to - stomach and pancreas.

4. Right is pyramidal-shaped and left is semi-lunar and slightly larger.

List the layers of the adrenal gland.

1. Capsule

2. Outer cortex - 3 layers

4. Inner medulla.

What does the cortex of the adrenal gland develop from + secrete

Mesoderm

secreates steroid hormones like Mineralocorticoids (e.g., aldosterone), glucocorticoids (e.g., cortisol), and weak androgens (e.g., DHEA)

What is the embryological origin of the outer cortex, what does it secrete and what controls this? (3)

1. Originates from mesoderm (like gonads).

2. Secretes steroid hormones with cholesterol precursors, controlled by pituitary.

3. Produces: mineralocorticoids (RAAS), glucocorticoids (cortisol + corticosterol) and androgenic steroids.

What is the embryological origin of the inner medulla, what does it secrete and what controls this? (2)

1. Originates from neuroectoderm - neural crest (like SNS).

2. Has neuroendocrine function and secretes catecholamines (A + NA), controlled by SNS.

What are the zones of the cortex?

Zona glomerulosa - 'blobs' - make mineralocorticoids.

Zona fasiculata - 'strings' - make glucocorticoids.

Zona reticularis - 'network' - makes androgens.

MR Fat Guy Chris

M=medulla

C=Capsule

What do the cells of the cortex and medulla secreate

• Cortex Cells: Steroid hormone-secreting cells.

• Medulla Cells: Peptide hormone-secreting cells (catecholamines); act as a modified neural ganglion

What is the arterial supply and venous drainage of the adrenal glands?

Arteries: 3 suprarenals (superior from inf. phrenic, middle from AA and inferior from renal aa)

Veins: Right is from IVC, left is from L renal vv.

Describe the route of blood supply in the adrenal gland

Blood passes from outer cortex → inner medulla

{-Venous blood from sinusoid network}

{Arterial blood from medullary arterioles}

Gland is drained by single central vein

What are the microscopic branches of the arteries?

Suprarenal aa > arterioles > capsular aa > sinusoidal capillaries (between cells) > drain into medullary vein > suprarenal vv.

Sinusoidal capillaries have a lot of holes enabling secretion to go into blood system.

How is the adrenal medulla like a modified neural ganglion?

In normal SNS, a preganglionic fibre synapses with post. fibre and has a target cell.

In the medulla, there is a preganglionic fibre which directly targets medullary cells and stimulates them to secrete product very quickly. I.E., the secretory cell is equivalent to the post-ganglionic fibre in SNS.

What is the ultrastructure of a steroid-secreting cell from the cortex?

Has

- smooth ER

- lipid droplets and

- tubular cristae in mitochondria rather than long shelf-like cristae.

What is the ultrastructure of a peptide-secreting cell from the medulla?

Has

- rough ER and golgi

- granules (to package secretion)

- normal mitochondria

What are the pathologies of the cortex?

1. Hypoadrenalism - Addison's (no hormone secretion).

2. Hyperadrenalism (oversecretion).

Give different types of hyperadrenalism. (3)

XS mineralocorticoid: Conn's syndrome.

XS glucocorticoids: Cushing's syndrome.

Malignant tumour: All 3 in XS.

Ectopic ACTH syndrome from neuroendocrine lung tumour (small cell carcinoma): due to XS glucocorticoids.

What is phaeochromocytoma i.e. causes, consequences, diagnosis? (4)

Phaeochromocytoma - pathology of medulla.

1. Rare cause of 2º hypertension due to XS catecholamines which is continuous or sporadic (50% each)

2. Mostly benign tumour of neuroectoderm.

3. Can cause lethal disease due to CV complications.

4. Diagnosed with urinary catecholamines or metabolites (not usually plasma).

What are the symptoms of phaeochromocytoma? (3)

1. Severe headache

2. XS sweating

3. Palpitations

Give a summary of the adrenal gland function.

Where is cholestrol made and transported

made from = plasma LDL

It is used to transport free cholesterol from outer mitochondrial membrane —> across IMS → into mitochondrial matrix

what is the hypothalamus piturity adrenal axis regulated by

Only glucocorticoid

in the hypothalamus pituitary adrenal axis , what controls the endogenous circadian rhythms

Suprachiasmatic nucleus

What is the function of aldosterone

Promotes sodium (Na⁺) and water retention and potassium (K⁺) elimination in the kidneys (DCT and collecting ducts) during the formation of urine.

Explain how aldosterone is regulated

Stimulated by increased plasma K⁺ and the renin-angiotensin system (not significantly regulated by ACTH)

What is weak androgens

Function: In women, supports androgenic activity (e.g., pubic and axillary hair growth and libido); limited role in men.

• In females = pubic hair growth, libido

• in men = Negative contribution in men

Examples of Weak androgens 

DHEA, DHEAS, and androstenedione

How is weak androgens regulated

Primarily controlled by ACTH

• More ACTH → more weak androgens

• Less ACTH → less weak androgens

but does not affect CRH/ACTH feedback loop.

What is the function of cortisol

main one fore stress response and acts as a mineralocorticoid

It is a Exogenous hormone = activates –vie feedback loop = adrenal suppression

Explain what effect cortisol have on :

• Muscle 

• Liver

• Adipose tissue

• Skeletal muscle 

• Muscle : Catabolic effects. (breaking protein and stored Triglycer → FFA + glycerol )

• Liver: Stimulates gluconeogenesis (liver) and glycogen storage, Overall elevating plasma glucose.

• Adipose tissue = DECREASES GLUCOSE UPTAKE AND LIPOGENESIS  and INCREASES LIPOLYSIS. The FFa and glycerol go to the liver to INCREASE GLUCOSE

• Skeletal Muscle = DECREASES GLUCOSE UPTAKE via GLUT-4 , increases protein breakdowna n ddecreses protein synthesis

At high physiological levels what effect does cortisol have

Anti inflammatory and immunosupressive effects

Explain HOW cortisol does Anti inflammatory and immunosupressive effects 

Stimulates production of lipocortin-1, inhibiting phospholipase A₂ (PLA2) the enzyme that makes arachodonic acid and is the precursor for prostanpids and leukotriens,→  decreases inflammatory mediators

In terms of immunity , what effect does cortisol have at very high physiological levels

• Decreases number + activation of T-lymphocytes

• Decreases production of cytokines

• Stabilises lysosomes

• Decreases nitric oxide production → NO kills bacteria + helps mediate inflammation 

what are Glucocorticoid analogues

synthetic or naturally derived compounds that mimic the effects of cortisol

Act as an anti-inflammatory in:

• Asthma 

• COPD

• Skin conditons

• Rheumatoid arthritis 

Act as an immunosupresion in:

• Organ transplantation

Act as an Replacement therapy in:

• Addisons disease

Explain what happens with SNS and adrenaline in the stress response system ?

Increases cardiac output and ventilation

diverts blood to the muscle and the heart

uses glycogen and fat stores 

then activates CRH-ACTH-cortisol  axis

Once the CRH-ACTH-cortisol axis is activated what happens ?

shift protein and fat stores in favour of the increased glycogen store and plasma glucose availability

Amino acids become more available for tissue repair 

In terms of integrated stress response:What is the action of cortisol

• Promotes gluconeogenesis, lipolysis, and proteolysis, increasing blood glucose and energy availability.

• Provides amino acids for tissue repair post-damage

Chronic Stress and Elevated Cortisol = Long-term elevated cortisol can lead to …..

• muscle wasting

• hyperglycaemia

• gastrointestinal (GI) ulcers

• weakened immunity (related to Cushing’s syndrome).