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Endocrine > PBL 4 - Adrenal Glands > Flashcards

PBL 4 - Adrenal Glands Flashcards

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1
Q

Describe the structure of the adrenal glands.

A

Size: 4-6cm
Weight: 6-8g

Shape:
RIGHT - pyramidal
LEFT - semilunar

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2
Q

List the structures surrounding the adrenal glands.

A
  1. Perinephric fat

2. Renal fascia

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3
Q

Describe the blood supply of the adrenal glands.

A
  1. Inferior phrenic arteries
    a. Superior suprarenal arteries
  2. Abdominal aorta
    a. Middle suprarenal arteries
  3. Renal arteries
    a. Inferior suprarenal arteries
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4
Q

Describe the venous drainage of the adrenal glands.

A
  1. Medullary veins
    a. Exit via the hilum
    b. Form the suprarenal veins
  2. Suprarenal veins
    a. Right –> inferior vena cava
    b. Left –> left renal vein
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5
Q

What is the lymphatic drainage of the adrenal glands?

A

Para-aortic glands

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6
Q

What is the innervation of the adrenal glands?

What is the function of this innervation?

A

Sympathetic innervation via:

  1. Coeliac plexus
  2. Thoracic splanchnic nerves

Function:

  1. Innervation of chromaffin cells in medulla
  2. Stimulation of chatecholamine productin in the medulla
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7
Q

List the layers in the adrenal glands.

A
  1. Fibrous capsule
  2. Cortex
    a. Zona glomerulosa
    b. Zona fasciculata
    c. Zona reticularis
  3. Medulla
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8
Q

Describe the features of the different levels of the medulla.

A
  1. Zona glomerulosa
    a. Cells in round/ovoid clusters
    b. Fibrous trabeculae
    c. Small cells
    d. Fewer lipid droplets
    e. Prominent capillaries
  2. Zona fasciculata
    a. Narrow cords of cells
    b. Collagen strands between cords
    c. More lipid droplets
  3. Zona reticularis
    a. Irregular arrangement of cords/clusters
    b. Smaller cells
    c. Fewer lipid droplets
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9
Q

What are the functions of each layer of the adrenal cortex?

A

Zona glomerulosa:
1. Mineralocorticoid production (ADH)

Zona fasciculata
1. Glucocorticoid production (cortisol)

Zona reticularis
1. Androgen production

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10
Q

What are the histological features of the adrenal medulla?

A
  1. Large central vein

2. Chromaffin cells

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11
Q

Describe the general process of steroid hormone synthesis.

A
  1. Cholesterol is transported to the inner mitochondrial membrane via cytochrome P450 (rate limiting step)
  2. Cholesterol is converted to pregnenolone via StAR (steroidogenic acute regulatory protein)
    a. This involves cleaving side chains
  3. Pregnenolone undergoes further shortening of side chains
    a. Various enzymes involved, e.g. CYP11A1
  4. Intermediates are further modified by addition of substituents in a stereo-specific manner
    a. This forms different hormones
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12
Q

List the steps in the formation of cortisol, and important enzymes involved.

A
  1. Cholesterol
    a. StAR
  2. Pregnenolone
  3. 17-OH-pregnenolone
  4. 17-OH-progesterone
    a. 21 hydroxylase
  5. 11-deoxycortisol
    a. 11 beta hydroxylase
  6. Cortisol
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13
Q

Describe the mechanism of action of cortisol.

A
  1. Cortisol is lipid soluble and easily diffuses into the cell
  2. Intracellular glucocorticoid receptor is activated by binding to cortisol
  3. Hormone-receptor complex enters the nucleus and binds to DNA
    a. Happens at the glucocorticoid response element
  4. This acts as a transcription factor and stimulates production of mRNA
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14
Q

List some of the effects of cortisol.

A
  1. Stimulates gluconeogenesis (liver)
  2. Permissive effect on glucagon/NA
    a. Stimulates their effectt
    b. Inhibits insulin release
  3. Stimulates lipolysis (adipose)
    a. Releases FAs and glycerol
    b. Used for energy production
  4. Stimulates break down of muscle proteins
    a. Muscle wasting
  5. Increases blood pressure
  6. Growth and development of foetus
  7. Stimulates initiation of post-partum lactation
  8. CNS effects
  9. Anti-inflammatory effects
    a. Decreased circulating T cells and eosinophils
    b. Increased circulating neutrophils
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15
Q

List the steps in the synthesis of aldosterone, and the important enzymes involved.

A
  1. Cholesterol
    a. StAR
  2. Pregnenolone
  3. Progesterone
    a. 21 hydroxylase
  4. 11-deoxycorticosterone
    a. 11 beta hydroxylase
  5. Corticosterone
    a. 18 hydroxylase
  6. 15-OH-corticosterone
    a. Aldosterone synthase
  7. Aldosterone
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16
Q

Where are mineralocorticoid receptors found?

Study These Flashcards
A
  1. DCT of kidney
  2. Salivary/sweat glands
  3. Large intestine
  4. Brain
  5. Vascular tissue
17
Q

Describe the mechanism of action of aldosterone.

Study These Flashcards
A
  1. Aldosterone is lipid soluble and easily diffuses into the cell
  2. Intracellular mineralocorticoid receptor is activated by binding to aldosterone
18
Q

What is the function of aldosterone?

How does it do this?

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A
  1. Increases sodium and water excretion
  2. Increases H+ and potassium excretion

Upregulates the following channels:

  1. Na+/K+ ATPase
  2. Na+ channels
  3. K+ channels
  4. Na+/H+ exchangers
19
Q

How is cortisol production controlled?

Study These Flashcards
A
  1. Hypothalamus releases CRH
    a. Stimulated by: stress, time of day, illness
  2. Anterior pituitary secretes ACTH
  3. ACTH stimulates adrenal cortex
  4. Cortisol has a negative feedback action on CRH/ACTH
20
Q

Describe the mechanism of action of ACTH.

Study These Flashcards
A
  1. ACTH binds to ACTH (M2) receptor (G protein coupled)
  2. This causes a conformational change in the ACTH receptor, so the alpha subunit detaches and activates adenyl cyclase
    a. Activates cAMP
    b. Activates PKA
  3. Causes Ca2+ influx into cell, causing:
    a. Stimulation of cholesterol transport to mitochondria via cytochrome P450
    b. Increased transcription of genes encoding steroidogenic enzymes (e.g. 11 beta hydroxylase)
    c. Increased cortisol reaction
21
Q

How is aldosterone secretion controlled?

Study These Flashcards
A

Renin-angiotensin-aldosterone system

22
Q

Describe the mechanism of action of angiotensin II.

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A
  1. Angiotensin II binds to the AngII type 1 receptor in the adrenal gland (G protein coupled)
  2. Conformational change causes the alpha subunit to detach, which activates phospholipiase C
    a. Converts PIP2 into PIP3 and DAG
  3. PIP3 causes release of stored Ca2+, causing Ca2+ influx
  4. Ca2+ influx activates calmodulin-dependent protein kinases (CaMKs), which cause:
    a. Increased StAR transcription
    b. Increased cytochrome P450 action
    c. Increased aldosterone production
23
Q

Define Cushing’s syndrome and Cushing’s disease.

Study These Flashcards
A

Cushing’s syndrome: “condition resulting from excess corticosteroid hormones in the body”

Cushing’s disease: “Cushing’s syndrome when caused by a pituitary gland tumour”

24
Q

List the causes of Cushing’s syndrome.

Study These Flashcards
A
  1. Endogenous cortisol excess
    a. Cushing’s disease
    b. Ectopic ACTH syndrome
    c. Adrenal adenoma
    d. Adrenal carcinoma
    e. Pseudo-Cushing’s syndrome due to non-endocrine disease
  2. Iatrogenic cortisol excess
    a. Chronic glucocorticoid therapy
    b. Glucocorticoid therapy overdose
25
List some of the clinical features of Cushing's disease.
1. Facial plethora (swelling with blood) 2. Hair thinning 3. Hirsutism 4. Psychosis 5. Moon face 6. Hypertension 7. Muscle wasting 8. Osteoporosis 9. Central obesity 10. Weakness 11. Bruising 12. Diminished immune response 13. Striae
26
List the investigations used for Cushing's syndrome.
1. 24 hour free urinary cortisol levels 2. Overnight dexamethasone suppression test 3. Low dose dexamethasone suppression test 4. High dose dexamethasone suppression test 5. Diurnal rhythm of plasma cortisol 6. Insulin tolerance test 7. CRH test 8. ACTH levels 9. Inferior petrosal sinus sampling
27
How is an overnight dexamethasone test done?
1. Dexomethasone is a corticosteroid, therefore taking it would normally suppress ACTH release and therefore decrease cortisol levels 2. Therefore, if dexamethasone does NOT decrease cortisol levels, this means there is Cushing's syndrome
28
What does a high dose dexamethasone test show?
Differentiates between pituitary-dependent disease and ectopic ACTH syndrome PITUITARY DEPENDENT DISEASE: urine cortisol is LESS than 50% of the basal rate ECTOPIC ACTH SYNDROME: urine cortisol is MORE than 50% of the basal rate
29
List the methods of treating Cushing's syndrome.
1. Trans-sphenoidal pituitary adenomectomy 2. Bilateral adrenalectomy 3. Medical treatment a. Somatostatin analogues b. Steroidogenesis inhibitors c. GR antagonists 4. Pituitary radiotherapy 5. Surgical removal of other tumours
30
List the potential consequences of long term exposure to excess corticosteroids.
1. Cushing's syndrome 2. Diabetes 3. Depression/anxiety 4. Androgen disruption 5. Acne 6. Osteoporosis 7. Gynaecomastia
31
Give some examples of primary and secondary adrenocortical insufficiency. What tests are used to distinguish between them?
PRIMARY: 1. Addison's disease SECONDARY: 1. Withdrawal of suppressive glucocorticoid therapy 2. Hypothalamic or pituitary disease 3. Surgical removal of pituitary gland Tests to differentiate: 1. Synacthen test 2. Serum ACTH levels 3. Plasma renin activity
32
Define Addison's disease.
A syndrome resulting from inadequate secretion of corticosteroid hormones due to the progressive destruction of the adrenal cortex, characterised by progressive deterioration; most commonly caused by autoimmune destruction
33
List some causes of Addison's disease.
1. Autoimmune a. Adrenal cortex antibodies b. 21 hydroxylase antibodies 2. Tuberculosis 3. HIV/AIDS 4. Metastatic carcinoma 5. Bilateral adrenalectomy 6. Corticogenoid enzyme deficiency a. Congenital adrenal hyperplasia b. Drugs
34
List the biochemical findings in Addison's disease.
1. Glucocorticoid insufficiency 2. Mineralocorticoid insufficiency 3. ACTH excess 4. Adrenal androgen insufficiency
35
List the clinical features of Addison's disease.
1. Caused by decreased cortisol a. Weight loss b. Weakness c. Anorexia d. Hypoglycaemia e. Hyponatraemia f. Hypercalcaemia 2. Caused by decreased aldosterone a. Hypotension b. Shock c. Hyponatraemia d. Hyperkalaemia 3. Caused by increased ACTH a. Pigmentation of skin 4. Caused by adrenal androgen insufficiency a. Decreased body hair b. Decreased libido
36
List the investigations you might do to test for Addison's disease.
1. Morning serum cortisol 2. Synacthen test/high dose ACTH test 3. Serum ACTH levels 4. Serum electrolytes 5. Blood urea levels 6. Full blood count 7. Plasma renin activity 8. Plasma aldosterone 9. Plasma DHEA/DHEAs levels 10. Adrenal antibodies 11. CT/MRI
37
How is a synacthen test done? What does it show?
1. 250μg ACTH1-24 (synacthen) is given via intramuscular injection 2. Subsequent blood cortisol levels are checked at: a. 0 minutes b. 30 minutes c. 60 minutes RESULTS: Primary adrenal insufficiency - no increase in cortisol Secondary adrenal insufficiency - progressive increase in cortisol
38
How do you replace adrenal hormones?
Glucocorticoids: 1. Hydrocortisone 2. Cortisone Mineralocorticoids: 1. Fludrocortisone Androgens: 1. DHEA

Endocrine (5 decks)

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