Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ESR > Adrenal axis > Flashcards

Adrenal axis Flashcards

1
Q

Where does ACTH act?

A
  1. Adrenal cortex
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does POMC processing work?

A
  1. Expression of pre-POMC driven by CRH
  2. POMC is generated by the cleavage of a signal peptide
  3. Cleave POMC with PHC/endopeptidase: makes pro-ACTH and beta-LPH
  4. Pro-ACTH and beta-LPH cleaved to make:
  • Beta-endorphins
  • MSH (alpha, beta, gamma)
  • ACTH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What do the different zones of the adrenal cortex make?

A
  1. Zona glomerulosa (ZG): Aldosterone
  2. Zona fasiculata (ZF): Cortisol
  3. Zona reticulata (ZR): DHEA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is required for the production of hormones in adrenal cortex and what is the rate limiting step?

A
  1. Cholesterol is the start product of all
  2. Cholesterol side chain cleavage by P450CSCC in inner surface of inner mitochondrial membrane (locked away from aqueous surface
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the role of P450C11B2?

A
  • Gene duplicate of P450C11B1
  • P450C11B1:
    • aka 11ß-hydroxylase
    • hydroxylates 11-deoxycortisol in ZF to cortisol in ZF
    • hydroxylates DOC to corticosterone in ZG
  • P450C11B2:
    • aldosterone synthase in ZG
    • new functions: 18-hydroxylase and aldehyde synthase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What does the fetal adrenal cortex have?

A
  1. Includes the fetal zone:
  • Synthesis 16-hydroxy-androstenediol
  • In placenta converted to oestriol by P450AROM
  • Fetal zone atrophies in neonate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are the metabolic actions of cortisol?

A
  1. Increases plasma glucose:
  • Inhibits IMGD by GLUT4
  • Spare glucose metabolsim where possible
  • Increase hepatic gluconeogenesis
  • Increases availibility of gluconeogenic substrates:
    • Glycerol (by increasing lipolysis)
    • Free amino acids (increase protein catabolism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does cortisol spare glucose metabolism?

A
  1. Brain, erythrocytes and renal medulla entirely reliant on glycolysis –> so direct glucose to them
  2. Other tissues capable of using non-carbohydrates to derive reduced NADH/FADH2 for ATP synthesis
  3. NEFAs go through beta oxidation to make acetyl CoA (TCA)
  4. Use amino acids to go into TCA via 6 routes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How does cortisol induce hepatic gluconeogenesis?

A
  • Activates glucocorticoid receptor to increase expression of key gluconeogneic enzymes
    1. Glucose-6P to Glucose:
  • Glucose-6-phosphatase
    2. Fructose-1,6-P2 to Fructose-1-P
  • Fructose 1,6-bisphosphatase
    3. Oxaloacetate (OAA) to Phosphophenol pyruvate (PEP)
  • PEPCK = PEP carboxykinase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does cortisol increase gluconeogenic substrates?

A
  1. Increased expression of HSL
  • Increased glycerol from TAG
  • NB. NEFA cannot be used for gluconeogenesis
  1. Increased expression of endopeptidases:
  • Increased hydrolysis of proteins to liberate 6 gluconeogenic amino acids
  • AA goes to TCA cycle and used for gluconeogenesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the other hyperglyceamic hormones?

A
  1. Catecholamines
  2. Glucagon
  • Cortisol exerts permissive genomic actions:
    • Upregulates and increases activity and turnover of some of these hormones
    • Activated GR (bound to GREs) synergises with activated CREB (bound to CREs) in genes encoding relevant metabolic enzymes and increases speed of response
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is the solubility of hydrophobic cortisol increased?

A
  • Interaction with hydrophilic, globular proteins
  • Steroid binding globulins:
    • CBG (cortisol binding globulin/transcortin) - binds C21 steroids
    • SHBG (sex hormone binding globulin) - can bind C19 and C18 steroids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the non-metabolic actions of cortisol?

A
  • Negative feedback (CRH + ACTH)
  • Positive ionotropic action on heart, abnormal ECG
  • Increase renal blood flow/GFR/water clearance
  • Inhibits fibroblast proliferation/collagen formation (increased bruising/impaired wound healing)
  • Actions on mood and behaviour
  • Increase synthesis of surfactant
  • Anti-inflammatory/immunosupressant
  • Increase serum calcium (bone catabolism)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the difference between Cushing’s disease and syndrome?

A
  • Disease:
    • tumour over-producing ACTH in pituitary gland
  • Syndrome:
    • NOT due to ACTH piuitary tumour
    • Excess cortisol can come from:
      • Ectopic tumour producing too much ACTH:
        • Thyroid
        • Pancreas
        • Thymus
        • Lung
      • Functional ZF tumour
      • Chronic stress
      • NOT glucocorticoid resistance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the symptoms of increased corticosteroid actions?

A

1. Hyperglycaemia:

  • Increased gluconeogenesis (liver)
  • Increased glycogenolysis (liver + muscle)
  • Increased protein catabolism (muscle)
  • Insulin resistance (T2D)

2. Redistribution:

  • Increased lipolysis in extremities (HSL)
  • Increased central lipogenesis
  • Moon face + buffalo hump + abdominal adiposity

3. Increased bruising (weakened vessel walls)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What does moon face look like?

A
  1. Supraclavicular fat pads
  2. Plethoric face (+hirsutism): due to DHEA induction by cortisol
  3. Look quite red
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the immune supression symptoms of increased corticosteroid action?

A

1. Immune supression:

  • Anti-inflammatory action (PLA2) - decrease prostaglandins
  • Lymphatic/thymus involution
  • Antagonise cytokine action

2. Gastric ulceration (decreased gastric pH)

3. Osteoporosis - due to catabolic effects on bone :. see increase in Ca2+ in circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the effects of hyperandrogenism?

A
  1. Acne, male-pattern baldness + hirsutism
  2. Female pseudohermaphroditism (in utero - present with genital of more than one sex)
  3. Precocious puberty - early puberty
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why aren’t adrenal androgens relevant in a healthy male?

A
  1. Actions of DHEA swamped by testosterone
  • DHEA = 2% of total plasma androgen (but for women is major circulating androgen)
  • DHEA is very weak
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is DHEA and other androgens responsible for?

A
  1. Responsible for adrenarche:
  • Growth of pubic and axillary hair prior to puberty
  • Acne
  1. Substrate for post-menopausal oestrogen synthesis in periphery:
    * Important for oestrogen-dependent tumours in women
  2. Female
    * Pseudohermaphroditism (genetically female but male on external genitalia due to increasing amounts of androgen)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the electrolyte and fluid imbalances in increased coricosteroid action?

A
  1. Electrolyte and fluid imbalance:
  • Hypokalemia (?neuropathy) - due to effect on aldosterone receptors
  • Anti-natruiresis (less sodium excretion)
  1. Hypervolemic hypertension

(headaches/visual disturbances/?stroke)

22
Q

What are the symptoms of decreased corticosteroid action?

A
  1. Hypoglycaemia (T1D symptom)
  • Tiredness and weakness
  • Vomiting
  1. Hyperpigmentation:
    * Particularly skin creases and mouth (due to more MSH as a result of negative feedback on POMC)
  2. Hypoandrogenism:
  • Symptoms only evident in females
  • Failed adrenarche
  • Sparse axillary + pubic hair growth
  1. Electrolyte and fluid imbalance:
  • Natruiresis/Hyponatremia (?neuropathy)
  • Anti-kaliuresis (building up potassium levels)
  1. Polyuria (lead to polydipsia)
  2. Hypovolemic hypotension - low BP and volume
23
Q
A
24
Q

What is released during acute stress? Chronic stress?

A
  1. Catecholamines
  2. Cortisol (very catabolic effects)
25
Q

What kind of mental health effects do long term use of steroids induce?

A
  1. Anxiety
  2. Irrability
  3. Impaired cognition to depression
  4. Mania
  5. Psychosis
  6. Suicidal tendency
26
Q
A
27
Q

What are the symptoms of Cushing’s syndrome?

A
  1. Weight gain in upper body and trunk
  2. Skin changes incl. darkening of skin, easy bruising and purple stretch marks
  3. Excess hair growth or acne in women
  4. Menstrual disorders - infrequent/absent periods
  5. Fatigue and muscle weakness
  6. Personality changes or mood swings
28
Q

What are the diagnostic tests for Cushing’s syndrome?

A
  1. Late-night salivary cortisol:
  • Most widely used (v. sensitive but additional testing always needed due to false positives)
  • Cortisol should be v. low between 23:00-00:00 :. high may indicate Cushing’s syndrome
  1. Urine free cortisol:
  • 24hr urine free cortisol levels reflect cortisol secretions in day
  • :. should have elevated cortisol but may have normal levels if mild Cushing’s syndrome :. false negatives
  • Conditions that can increase urine free cortisol: depression, chronic alcoholism, eating disorders
  1. Low-dose dexamethasone supression test:
  • Synthetic steroid that would suppress cortisol production to v. low: <1.8µg/dl but in syndrome does not
  • 1mg dose at 11pm
  • False positives
  • Preferred for: suspected primary adrenal gland disorder
29
Q

What differential diagnosis methods are used for Cushing’s syndrome?

A
  1. ACTH levels
  2. CT of adrenal glands (if ACTH low :. cortisol must be high in adrenals)
  3. MRI pituitary (if ACTH high):
  • Gadolonium enhancement
  • NB. 10% of ectopic ACTH may also have pituitary tumour
  1. Inferior petrosal sinus sampling (if normal pituitary MRI and ACTH secreting tumour causing syndrome)
  • Administer CRH and measure before and after ACTH levels
  • Excellent diagnostic accuract
  • Reliably establish presence or absence of an ACTH secreting pituitary tumour
30
Q

How does inferior petrosal sinus sampling work?

A
  • Used to distinguish between ACTH secreting tumour and pituitary tumour
  • Use CRH stimulation for accuracy
  • Petrosal:Peripheral >2 indicating Cushing’s disease
  • If no response to CRH then ectopic ACTH syndrome
31
Q

When would you do ACTH stimulation?

A

When Addison’s disease is suspected

32
Q

What are the drugs used to treat Cushing’s syndrome?

A
  1. Ketoconazole:
  • SE: liver damage
  • Most used
  • Blocks production of cortisol
  1. Mitotane:
  • Blocks production of cortisol
  • SE: may also cause destruction of adrenal cells
  1. Metyrapone:
    * SE: facial hair growth in women, swelling, low potassium, dizziness
  2. Mifepristone:
  • Blocks the action of cortisol in body
  • CI: pregnancy
  1. Cabergoline:
  • Effects wear off over time
  • Usually used for prolactin secreting tumours
33
Q
A
34
Q

Why do you get CAH?

A

Mechanism:

  1. Loss of function mutations/decreased expression of adrenal stereoidogenic enzymes
  2. Little or no synthesis of cortisol or corticosterone
  3. Decreased negative feedback
  4. Elevated ACTH causes hyperplasia
35
Q

Which gene is mutated in salt-wasting CAH?

A
  • CYP21 - encodes P450C21

:. cannot make aldosterone and cannot make cortisol

Lack of aldosterone = sodium excreted

Lack of cortisol = Increased ACTH :. Increased DHEA

36
Q

Which gene is mutated in salt-sparing/simle-virilisning CAH?

A
  • P450C11B1
  • milder compared to salt-wasting because can make DOC:
  • Weak mineralocorticoid :. can weakly act instead of aldosterone
  • But no cortisol :. therefore ACTH increase
  • :. lots of DOC produced :. fluid balance detected as high but aldosterone cannot be turned off as it is not the cause of this
  • Lead to maligant hypertension (driven by excess ACTH)
37
Q

Why do NOT get hirsutism in iatrogenic Cushing’s?

A
  • Cushing’s syndrome would be due to excess ACTH which also stimulates DHEA production
  • However iatrogenic syndrome, giving pure glucocorticoids so no stimulation of DHEA
38
Q

Why do you need to wean off someone of their GC?

A
  1. Exogenous glucocorticoids supress CRH/ACTH axis

:. adrenal cortex becomes smaller as no action

:. can atrophy and lead to iatrogenic Addison’s disease

39
Q

What causes hypolaemia, anti-natruiresis and hypervolemic hypertension?

A
  1. Mineralcorticoids
  2. Glucorticoids
  • Actions via MR
  • Aldosterone and excess cortisol
40
Q

Why do you get more bruising?

A
  • Glucocorticoids:
    1. less muscle and adipose to protect blood vessels
    2. supressed proliferation of fibroblasts
    3. impaired collagen synthesis
41
Q

What causes gastric ulceration?

A
  1. Glucocorticoids
  • Acid attack gastric mucosa inhibited by prostaglandins
  • Prostaglandin synthesis inhibited by glucocorticoids (via increased lipocortin/Annexin)
42
Q

What causes cliteromegaly?

A
  1. Increased DHEA
  2. Leading to increased testerone
  3. Leading to 5a-DHT
43
Q

What is Conn’s syndrome?

A
  • Primary (benign tumour of adrenal gland)
  • Secondary hyperaldosteronism:
    • Related to high blood pressure
    • Related to cirrhosis of the liver, heart failure, or over-activity of the renin-angiotensin sysem (e.g. renin producing tumour)
44
Q

What are the symptoms of Conn’s syndrome?

A
  1. Fatigue
  2. Headache
  3. High BP
  4. Intermittent paralysis
  5. Muscle weakness
  6. Numbness
45
Q

What are the signs and test of Conn’s syndrome?

A
  1. Abdominal CT scan that shows adrenal mass
  2. ECG shows heart rhytm abnormalities due to low potassium levels
  3. Elevated plasma aldosterone level
  4. Elevated urinary aldosterone
  5. Low plasma renin activity (negative feedback?)
  6. Low serum potassium level
46
Q

What is Conn’s specifically?

A
  1. Unilateral adenoma of adrenal gland :. too much aldosterone
  2. If bilateral : bilateral adrenal hyperplasia
  3. Most cases occur in people between 30-50 years of age
  4. Spironoloctone acts as an anti-androgen, aldosterone antagonist and mild potassium diuretic
47
Q
A
48
Q

What is the treatment of Conn’s syndrome?

A
  1. Laproscopic adrenalactomy after CT scan
49
Q

What is Nelson’ syndrome?

A
  1. Iatrogenic:
  • If pit. adenoma not detected
  • Adrenals removed to reduce cortisol
  • Pit. tumour not removed :. ACTH production keeps going up = Nelson’s syndrome 1-4 years after surgery in 15-20% of patients
  1. Occurs as a result of bilateral adrenalectomy
  2. Treatment: transphenoidal surgery to remove pituitary tumour
  3. Common signs and symptoms: muscle weakness, skin hyperpigmentation due to excess MSH
  4. Now rare as bilateral adrenalectomy is now only used in extreme cases
50
Q
A

ESR (7 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions