Exam #4: Adrenal Physiology Flashcards Preview

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Flashcards in Exam #4: Adrenal Physiology Deck (34)
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1
Q

Outline the HPA axis & the control mechanisms of the HPA axis.

A

The HPA axis regulates GLUCOCORTICOID production, which in humans is 95% cortisol

2
Q

What are the zones of the adrenal cortex?

A

From outer to inner:

1) Zona glomerulosa
2) Zona fasciculata=
3) Zona reticularis

3
Q

What are the main steroid hormones that are secreted by each of the zones of the adrenal cortex?

A

1) Zona glomerulosa= aldosterone (minercorticoid)

2) Zona fasciculata= primarily glucocorticoids
- Cortisol
- Corticosterone

3) Zona reticularis= primarily androgens
- Dehydroepiandosterone (DHEA)
- Andorostenedione

4
Q

Outline the pathways of cortisol, aldosterone, and the adrenal androgen synthesis.

A

N/A

5
Q

What is the function of 17a-hydroxylase? What is the clinical outcome of a deficiency in 17a-hydroxylase?

A

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6
Q

What is the function of 3B-hydroxysteroid dehydrogenase? What is the clinical outcome of a deficiency in 3B-hydroxysteroid dehydrogenase?

A

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7
Q

What is the function of 21-hydroxylase? What is the clinical outcome of a deficiency in 21-hydroxlase?

A

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8
Q

What is the function of 11B-hydroxylase? What is the clinical outcome of a deficiency in 11B-hydroxylase?

A

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9
Q

How does ACTH increase adrenal steroid synthesis?

A

Generally, ACTH stimulates the rate-limiting steps in cortisol synthesis. Specifically,

1) MC2R–>Gas–>cAMP–>PKA–>phosphorylation of cholesterol ester hydrolase, increasing availability of free cholesterol
2) Increased synthesis of StAR (Steroid Acute Regulatory Protein)
3) Increases activity of cholesterol desmolase

10
Q

What are the physiological effects of cortisol?

A

1) Metabolic= increased blood glucose
- Increased gluconeogensis
- Degradation of muscle & prevention of protein synthesis
- Lipolysis in fat cells
- Stimulation of hepatic glycogen synthesis

2) Anti-inflammatory= decreased synthesis of the precursor to prostaglandins & leukotrienes
3) Immunosuppressive= decreased lymphocyte production
4) Vascular reactivity= maintains the responsiveness of vascular smooth muscle to catecholamines

*****Note that in fetal development, glucocorticoids promote lung development

11
Q

What are the physiological effects of aldosterone?

A

Generally, aldosterone functions to increase Na+ & H20 REABSORPTION & K+ SECRETION in the distal convoluted tubule & collecting ducts of the kidney

12
Q

How does cortisol increase plasma glucose levels?

A

Cortisol increases plasma glucose by a variety of mechanisms including:

1) Increased gluconeogenesis
2) Muscle degradation and decreased amino acid uptake (shunted into gluconeogenesis)
3) Lipolysis of fat (shunted into gluconeogenesis)

13
Q

How does aldosterone increase water and Na+ reabsorption?

A

1) Expression of the amiloride sensitive epithelial sodium channel (ENaC)
2) Expression of the basolateral Na+/ K+ ATPase pump

14
Q

List the catcholamines released by the adrenal medulla.

A

NE
Epi
DA

15
Q

How does cortisol regulate synthesis of epinephrine?

A

The catecholamines are synthesized from tyrosine. Eventually, DA is packaged into secretory vesicles, and in the vesicles, DA can be converted to NE. NE leaks into the cytoplasm.

  • **The cytoplasmic enzyme, PNMT converts NE into Epi.
  • Cortisol increases the expression of PNMT, and thus increases concentrations of Epi.
16
Q

How does cortisol facilitate the effects of NE & epinephrine?

A

Cortisol maintains the responsiveness of the vascular smooth muscle to NE & Epi

17
Q

What causes Cushing’s Syndrome?

A

Chronic glucocorticoid excess i.e. excess cortisol, leads to Cushing’s Syndrome

18
Q

What are the symptoms of Cushing’s Syndrome?

A
HTN 
Hypokalemia 
Buffalo hump 
Moon face 
Muscle wasting 
Emotional problems 
Increased susceptibility to infection 
Hyperglycemia

Virilization & hirsutism from excess androgens

19
Q

Outline the pathophysiology of Cushing’s Syndrome.

A

1) Pituitary tumor hypersecreting ACTH
2) Chronic glucocorticoid therapy
3) Ectopic hypersecretion of ACTH
4) Hypersecretion of CRH
5) Adrenal tumor hypersecreting cortisol
6) Iatrogenic from exogenous glucocorticoid administration

20
Q

What is the general difference between primary and secondary adrenal insufficiency?

A

Adrenal insufficiency refers to a dysfunction of the adrenal cortex & deficient secretion of cortisol & aldosterone

  • Primary= damage to the adrenal cortex
  • Secondary= suppression of ACTH induced cortisol production
21
Q

What causes primary adrenal insufficiency?

A

Primary adrenal insufficiency is caused by autoimmune destruction of the adrenal cortex, infection, and cancer

22
Q

What causes secondary adrenal insufficiency?

A

Secondary adrenal insufficiency is caused by suppression of ACTH- induced cortisol production

  • Hypothalmic or pituitary disorder
  • Chronic exogenous glucocorticoid administration
23
Q

What are the symptoms of primary adrenal insufficiency?

A
  • Postural hypotension
  • Hyponatremia
  • Hyperkalemia
  • Hypoglycemia
24
Q

What are the symptoms of secondary adrenal insufficiency?

A
  • Postural hypotension
  • Hyponatremia
  • Hyperkalemia
  • Hypoglycemia

**Note that these can be life-threatening in the abrupt cessation of exogenous glucocorticoid administration

25
Q

What are the symptoms of 21-hydroxylase deficiency?

A

This is a steroid hormone biosynthesis disorder that called “congenital adrenal hyperplasia.” Symptoms include:

1) Increased growth of the adrenal cortex
2) Females born with male sex characteristics/ males with early development of adult characteristics
3) “Salt Wasting” leading to:
- Hypotension
- Hyponatremia
- Hypokalemia

26
Q

Outline the pathophysiology of 21-hydroxylase deficiency..

A

Without 21-hydroxylase, aldosterone and cortisol cannot be produced; rather, the androgens are synthesized.

  • Decreased cortisol leads to increased ACTH
  • Elevated ACTH leads to growth of the adrenal cortex & increased production of the androgens (again b/c aldosterone & cortisol cannot be produced)
27
Q

Where is the receptor for CRH?

A

Corticotroph cells of the anterior pituitary

28
Q

What is pro-opiomelanocortin?

A

The large precursor protein of ACTH, which is also called POMC for short

29
Q

List the POMC cleavage products.

A

1) ACTH
2) Melanocyte-stimulating hormones
3) Endogenous opioid peptide

30
Q

What is the receptor for ACTH? Where is this receptor located?

A

Melanocortin 2 Receptor (MC2R), which is located on the surface of the adrenal cortex

31
Q

Describe the fluctuations of cortisol throughout the day. What is the clinical significance?

A
  • ACTH release follows a circadian rhythm and is higher just before and after waking
  • Consequently, cortisol levels are highest in the morning

*****If glucocorticoid deficiency is suspected, cortisol levels should be measured early in the morning,

32
Q

How does cortisol exert negative feedback on the anterior pituitary and hypothalamus.

A

Binding to the glucocorticoid receptor (GR)

33
Q

What is the function of StAR?

A

This the Steroid Acute Regulatory Protein, it transports cholesterol into the inner mitochondrial membrane

34
Q

MR’s have a similar affinity for cortisol and aldosterone & cortisol concentrations are much higher in the plasma, what prevents cortisol action at these receptors?

A

Expression of an enzyme by aldosterone target tissues that cleaves cortisol into inactive cortisone

*****Note that in states of cortisol excess, these enzymes are saturated and cortisol will bind & activate MR’s

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