LMP301 Lecture 9: Adrenal Disease Flashcards Preview

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Flashcards in LMP301 Lecture 9: Adrenal Disease Deck (87)
1

Where are the adrenal glands?

On top of the kidneys

2

What happens to the adrenal gland during stressful situations?

enlarge

3

Adrenal gland is divided into...

- cortex
- medulla

4

The cortex of the adrenal gland is divided into...

- zona glomerulosa
- zona fasciculata
- zona reticularis

5

The adrenal medulla is a part of the...

SNS

6

Zona glomerulosa secretes....

aldosterone

7

zona fasciculata secretes...

- cortisol
- adrenal androgens & estrogens

8

zona reticularis secretes...

- cortisol
- adrenal androgens & estrogens

9

The adrenal medulla secretes...

- E
- NE
- Dopamine

10

What is the first enzyme to act on cholesterol during the biosynthesis of steroid hormones?

Cholesterol side chain cleavage hormone

11

What are the steroid hormones?

- aldosterone
- cortisol
- testosterone

12

ACTH

Signal needed for biosynthesis of steroid hormones

13

Enzyme cascade for aldosterone synthesis

1. Cholesterol side chain cleavage hormone
2. 3B-hydroxysteroid dehydrogenase
3. 21 OH'ase
4. 11 OH'ase
5. 18 OH'ase

14

Enzyme cascade for cortisol synthesis

1. Cholesterol side chain cleavage hormone
2. 17 OH'ase
3. 3B-hydroxysteroid dehydrogenase
4. 21 OH'ase
5. 11 OH'ase

15

Enzyme cascade for testosterone synthesis

1. Cholesterol side chain cleavage hormone
2. 17 OH'ase
3. 17,20 OH'ase
4. 3B-hydroxysteroid dehydrogenase
5. 21 OH'ase

16

Which enzyme is unique to aldosterone synthesis?

18 OH'ase

17

Pathway of aldosterone synthesis

1. Cholesterol
2. Pregnenolone
3. Progesterone
4. Deoxycorticosterone
5. Corticosterone
6. Aldosterone

18

Pathway of cortisol synthesis

1. Cholesterol
2. Pregnenolone
3. 17-OH pregnenolone
4. 17-OH progesterone
5. 11-deoxycortisol
6. Cortisol

19

Pathway of testosterone synthesis

1. Cholesterol
2. Pregnenolone
3. 17-OH pregnenolone
4. DHEA
5. Androstenedione
6. Testosterone

20

Cortisol can affect...

metabolism of carbs, proteins, and fat

21

Effect of cortisol on carb metabolism

Raise blood glucose
- gluconeogenesis in liver
- reduce glucose used and stored

22

Effect of cortisol on protein metabolism

Break down muscle

23

Effect of cortisol on fat metabolism

Break down fat

24

What happens when glucocorticoids are present in excess?

cause central distribution of fat -> goes to face, neck, trunk

25

How do cortisol travel in the body?

90 - 98% is bound to proteins
- albumin
- cortisol binding globulin (CBG)

26

When can an increase of CBG be found?

- Pregnancy
- Estrogen treatment

27

How is cortisol metabolized in the body?

1. Liver
2. Excreted in urine

28

Axis that controls cortisol secretion

Hypothalamic-pituitary-adrenaocortical axis
1. Hypothalamus -> CRH
2. a. pituitary -> ACTH
3. adrenal cortex -> cortisol

29

Feedback of cortisol

Cortisol inhibits ACTH and CRH

30

What stimulates production of CRH?

Stress
Sleep/wake

31

What is too much cortisol called?

Cushing's syndrome

32

Possible causes of Cushing's syndrome

- tumour at pituitary (ACTH overproduction)
- ectopic ACTH
- adrenal gland tumour (excess cortisol)
- exogenous glucocorticoids

33

Ectopic ACTH

ACTH produced by cells other than the pituitary

34

What cells may produce ACTH, other than pituitary?

small cell carcinoma in the lung

35

some sources of exogenous glucocorticoids

- oral
- inhaled
- topical creams

36

Clinical features of Cushing's Syndrome

- Acne
- Moon face
- Osteoporosis
- abdominal fat
- stripes on abdomen
- high BP
- buffalo hump

37

At what time during the day is cortisol levels the highest?

Morning

38

What is used to screen for Cushing's?

24h urine test:
- High cortisol in the urine
- Can also be caused by stress & obesity

39

What tests are used to diagnose Cushing's?

- plasma cortisol
- low dose dexamethasone test
- high dose dexamethasone test
- plasma ACTH

40

dexamethasone is...

a cortisol analogue

41

When is plasma cortisol measured?

8AM
10 PM

42

What is looked for in a plasma cortisol test?

Cortisol will not vary with time of day in patients with Cushing's

43

What is looked for in a low dose dexamethasone test?

- normal: slow cortisol production by 50%
- Cushing's: can't slow cortisol production

44

What is looked for in a high dose dexamethasone test?

- Cushing's disease: slow cortisol productivity by 50%
- Other causes: will not slow cortisol productivity

45

Why is high dose dexamethasone test used?

Which of the Cushing's syndrome causes it was

46

Difference between Cushing's disease and syndrome

Disease: cause is specifically a pituitary tumour producing too much ACTH

Syndrome: tissues being exposed to too much cholesterol for too long

47

What is looked for in plasma ACTH?

- high ACTH = ectopic ACTH tumors
- low ACTH = adrenal tumours

48

What order are tests used to diagnose Cushing's?

1. Screening: plasma cortisol
2. Confirmation: low dose dexamethasone
3. Differential diagnosis of cause: high dose dexamethasone; plasma ACTH

49

Cortisol is the counter hormone of...

insulin

50

Aldosterone is only produced in the zona glomerulosa because...

- doesn't have 17 OH'ase
- have 18 OH'ase
- have 18 hydroxysteroid dehydrogenase

51

What regulates aldosterone production and secretion?

- Renin-ANG II system (major)
- ACTH
- Potassium

52

Biological effect of aldosterone

Raise BP:
- Na and H2O retention
- K and H secretion

53

Why is hypertension seen in patients with Cushing's?

all cortisol precursors and cortisol have some kind of mineralocorticoid effects (SAME EFFECT AS ALDOSTERONE)

54

Renin is released in response to...

- Low tubular Na+
- Low BP at renal arteries
- SNS stimulation

55

Increased K+ has what effect on aldosterone?

Stimulates secretion/production

56

ACTH has what effect on aldosterone?

Very little effect, especially in normal situations

57

Function of renin

angiotensinogen -> ANG I

58

Function of ACE

ANG I -> ANG II

59

Clinical features of excess aldosterone

- high BP
- neuromuscular weakness due to lack of K+
- polydipsia & polyuria

60

Why is a symptom of excess aldosterone polydipsia & polyuria?

- hypokalemia causes ADH resistance = more water secreted

61

nephrotic diabetes insipidus is caused by...

ADH resistance

62

High aldosterone is...

Conn's syndrome
Low-renin hyperaldosteronism

63

High aldosterone is usually due to...

adrenal tumours

64

Conn's syndrome is ___ hyperaldosteronism

primary

65

Secondary hyperaldosteronism = high ___

renin

66

Secondary hyperaldosteronism is usually associated with...

renal, heart, liver disease

67

Secondary hyperaldosteronism is also known as...

renal artery stenosis

68

Which type of hyperaldosteronism is more common?

secondary

69

Primary hyperaldosteronism: sequence of events

1. adrenal gland secretes a lot of aldosterone
2. aldosterone causes increased Na+ retention & increase K+ loss
4. High Na+ causes decreased renin
5. causes decreased ANG II

70

Secondary hyperaldosteronism: sequence of events

1. Decreased blood flow at renal artery
2. Increased renin
3. Increased ANG II
4. Increased aldosterone
5. Increased Na+ retention
6. Increased K+ loss (also caused by high aldosterone)

71

Diagnosis of hyperaldosteronism

- low K+ (a lot excreted)
- High aldosterone
- renin low (primary)
- renin high (secondary)

72

Acid-base status in patients with hyperaldosteronism?

Metabolic alkalosis (H+ secreted because Na+ is retained)

73

Low aldosterone is ___ disease

Addison's

74

Addison's disease (and what is it due to?)

Low aldosterone
- Due to autoimmune destruction of the cortex

75

Causes of hypoadrenalism

- Autoimmune destruction of cortex
- Gland destruction caused by tuberculosis, infections, cancer
- Secondary / tertiary hypoadrenalism caused by ACTH deficiency (pituitary / hypothalamus problem)
- Long-term corticosteroid therapy: breaks the HPA axis

76

Difference between primary and secondary and tertiary hypoadrenalism

- primary: problem at adrenal gland (ACTH high)
- secondary: problem at a. pituitary (ACTH low)
- tertiary: problem at hypothalamus (CRH low)

77

Clinical features of hypoadrenalism

- lethargy
- anorexia
- weight loss
- increased pigment in hand and mouth (Addison's)
- abdominal pain

78

Why is there increased pigment for Addison's?

melanocyte-stimulating hormone is secreted along with ACTH (which is secreted in high amounts)

79

Acute crisis for hypoadrenalism

- dehydration
- hypotension
- nausea
- vomiting

80

Biochemical features of hypoadrenalism

- low NA+
- high K+
- mild metabolic acidosis
- hyperuremia
- hypoglycemia
- high ACTH (primary)

81

Diagnosis of hypoadrenalism

Short Synacthen test

82

Problem with testing serum aldosterone

Have to have normal to compare to (the normal must be from the same person)

83

Synacthen is a ____ analogue

1-24 ACTH

84

Short Synacthen test is also called...

ACTH stimulation test

85

Short Synacthen test

1. measure serum cortisol
2. give synacthen
3. measure cortisol 30 min later

86

Interpreting short Synacthen test

Normal: cortisol rise rapidly
Addison's: no change
Adrenal atropy: slight rise

87

Anti-hypertensive agents used (RAAS)

- ACE inhibitor
- ANG II receptor blocker
- Block aldosterone receptor
- Block renin receptor