Bsf Exam 4: Adrenal Gland

Front 1

Describe how norepinephrine in the cytoplasm is converted to epinephrine in the chromaffin granule

Back 1

Norepinephrine is synthesized in the secretion granule, and then moves into the cytoplasm where almost all is converted to epinephrine by the cytoplasmic enzyme PNMT. Epinephrine is actively transported back into the granule for secretion

Front 2

How does epinephrine influence metabolic pathways in the liver?

In adipose tissue?

Back 2

Epinephrine acts as a counter-regulatory hormone at the liver, it stimulates glycogenolysis, gluconeogenesis, and ketogenesis.

At the adipocyte, epinephrine has a strong lipolytic action through the activation of hormone sensitive lipase (HSL)

Front 3

Explain how catecholamines can cause vasoconstriction in some blood vessels, while causing vasodilation in others

Back 3

Catecholamines act through binding to adrenergic receptors. The primary action on a given organ will be determined by the relative density of the different adrenergic isotypes. The beta2 adrenergic receptor is coupled to the Gs/cAMP/PKA pathway, which promotes vascular smooth muscle relaxation and thus, vasodilation.

Other vessles have alpha-1 receptors which would trigger constriction.

Front 4

Why may the adrenal cortex atrophy when synthetic glucocorticoids are administered?

Back 4

Exogenous glucocorticoids inhibit ACTH, which normally is tropic to the adrenal cortex.

Front 5

Why may masculinization of women (adrenogenital syndrome) occur in patients with Cushing's disease?

Back 5

Excessice ACTH will drive adrenal androgen synthesis in the zona reticularis. The high levels of weak androgens lead to higher levels of testosterone and DHT bring produced peripherally in such cells as hair follicle cells.

Front 6

Explain the interaction of ENaC and SGK-1 in the actions of aldosterone

Back 6

Aldosterone increases the synthesis of ENaC (alpha su). Aldosterone also increases Sgk-1 gene expression. Sgk-1 prevents the ability of a protein, called Nedd 4-2, from trageting ENaC for degradation. Thus aldosterone promotes Na+ reabsorption by increasing the synthesis and stability of ENaC in the apical membrane of the distal tubule.

Front 7

Explain the differences between the cause of orthostatic hypotension in patients with orthostatic hypotension associated with pheochromocytoma and orthostatic hypotension associated with Addison's disease

Back 7

Orthostatic hypotension is due to loss of sympathetic tone to adjust for th epull of gravity on the blood. A pheochromocytoma produces chronic high levels of catecholamines , which down regulate all adrenergic receptors.
In Addisons disease, very low levels of aldosterone deplete the intravascular volume, reducing blood pressure. Low cortisol will decrease angiotensinogen production by the liver, and decreases adrenergic receptor expression (especially alpha1) and signaling in blood vessels. Further, very low levels of cortisol decrease PNMT levels, and thus, adrenomedullary production of epinephrine

Front 8

Why are the consequences of a secondary pituitary ACTH insufficiency generally less severe than those of a primary adrenal insufficiency?

Back 8

Primary adrenal insufficiency involves aldosterone and glucocorticoid production, whereas secondary insufficiency involves only glucocorticoid production.

Front 9

What substances are produced by the Adrenal Cortex?

The Adrenal Medulla (a specialized sympathtic ganglion)?

Back 9

Adrenal Cortex produces Steroids (from cholesterol)

Adrenal Medulla produces Catecholamines (EPI. NE, dopamine)

Front 10

How does ACTH stimulate the synthesis of steroid hormones?

Back 10

ACTH stimulates steroid synthesis by two mechanisms:

1. Stimulates the uptake of cholesterol from LDL via LDL-receptors and the storage of free cholesterol in lipid droplets

2. Stimulates formation of pregnenolone in mitochondria - the rate-limiting step

Front 11

How are adrenal steroids transported in circulation?

Back 11

Corticosteroid hormones are bound to plasma proteins in the circulation: Either by corticosteroid-binding globulin called transcortin (major transport protein) or by albumin.
*bound hormones are inactive

It's important to remember that only free forms (unbound) of steroids are biologically active.

Front 12

Adrenal steroids are metaboized by the ___ and excreted by the ____.

Back 12

Liver, Kidneys

Front 13

How is secretion of adrenal steroids regulated?

Back 13

Secretion of adrenal steroids is regulated by hypothalamo-pituitary adrenal pathway.

CRH -->ACTH --> Adrenal steroids
CRH is stimulated by Hypoglycemia,
Inflammation (via proinflammatory cytokines), Hemorrhage,
Neurogenic stress (fear, trauma, anesthesia, surgery)

Cortisol can feedback (neg) to inhibit:
CRH, and ACTH secretion (fast response, minutes) and synthesis (slow response, hours)

Front 14

At what time of the day are blood concentrations of ACTH and cortisol the highest?

At what time are they lowest?

Back 14

Peak levels occur in early morning (5-8 am)

Low levels occur in late evening (8pm - 3am)

Front 15

What are some factors that can override the diurnal (night-day) pattern of cortisol release?

Back 15

Stress, sever pain and prolong exercise increase cortisol release

Analgesia (opiates, endorphins) decreases cortisol release

Front 16

How are the effects of cortisol mediated? Where are the receptors located?

Back 16

Effects of cortisol are mediated via transcriptional mechanisms. It modifies gene expression via a cytoplasmic-nuclear protein receptor.

Front 17

What are the three major effects of cortisol?

Back 17

Energy metabolism: Cortisol increases plasma glucose level

Anti-inflammation:Cortisol suppresses function of the immune system

Anti-stress: Cortisol mediates adaptation to long-term stress

Front 18

Describe cortisol effects on energy metabolism

Back 18

Cortisol is catabolic. It...

Stimulates mobilization of AAs & their conversion to glucose

Stimulates gluconeogenesis

Causes the breakdown of skeletal muscle proteins

Enhances lipolysis

Causes negative calcium balance (decreases intestinal absorption, increases renal excretion, causes loss of calcium from bone tissue)

Front 19

Describe cortisol's effect on muscle metabolism

Back 19

The overall effect is to stimulate the conversion of protein to glucose and the storage of glucose as glycogen (increase glycogenolysis).
Net protein catabolic actions result in ↑ amino acid levels in plasma (via proteolysis), which increases their availability for gluconeogenesis.
Cortisol increases plasma glucose levels resulting from ↓ glucose utilization and uptake:
Cortisol reduces tissue sensitivity to insulin (decreased GLUT-4 glucose uptake)

Front 20

Describe cortisol's effect on fat metabolism

Back 20

Cortisol increases plasma fatty acids and glycerol levels by enhancing lipolysis
Via stimulation of lipolytic enzymes (hormone sensitive lipase)
Also directly inhibits lipogenesis
decreases GLUT-4 glucose uptake by adipocytes

Front 21

Describe cortisol effects on liver metabolism

Back 21

In the liver:

Cortisol stimulates gluconeogenesis, plasma protein synthesis, and glycogen synthesis /storage

Cortisol increases hepatic plasma protein synthesis

Front 22

What are the anti-inflammatory actions of cortisol?

Back 22

Stabilizes Lysosomes
↓ Proteases & Histamine (reduces pain and function loss)

↓ Capillary Permeability
↓ Edema & Exudation (reduces swelling, pain and function loss)

↓ Blood Flow
↑ Vasoconstriction
↓ Vasodilation
↓ WBC Infiltration (reduces redness, swelling, heat, and pain)

↓ Immune Response
↓ Cytokines
↓ B & T Lymphocytes (prevents autoimmunity)

Front 23

Describe what happens in acute stress (ie. hip dislocation)

Back 23

Cortisol increases
↓insulin/glucagon ratio
↑ Epi and Norepi
In the Liver:
↑glycogenolysis
↑gluconeogenesis

Skeletal muscle:
↑increased proteolysis
↓protein synthesis
increased glycogenlysis
↓GLUT4-mediated glucose uptake

Adipose tissue:
↑ lipolysis;
↓ lipogenesis,
↓GLUT4-mediated glucose uptake

Front 24

Describe what happens in chronically elevated levels of cortisol (ie. In Cushing's disease)

Back 24

Increased cortisol.
↑ insulin/glucagon ratio
↓ Epi and Norepi

CNS:
↑ appetite

Liver:
↑glycogen synthesis

Skeletal muscle:
↑ proteolysis
↓GLUT4-mediated glucose uptake

Adipose tissue:
↓ lipolysis
↑ triglyceride synthesis
↓GLUT4-mediated glucose uptake

Front 25

What is the primary mineralocorticoid?

What stimulates its secretion?

What inhibits release?

Back 25

Aldosterone is the primary mineralocorticoid.

Secretion is stimulated by the renin-angiotensin system:
- Angiotensin II (direct effect)
- High plasma [K+] (direct effect
- ACTH (direct effect)
- Hypotension (indirect effect via renin-angiotensin system)

Inhibited by ANP (directly and indirectly)

Front 26

What are the effects of aldosterone?

Back 26

Aldosterone is the major regulator of Na+, K+,(electrolyte homeostasis) and fluid balance:
(Primary effect) Increases Na+ reabsorption (in) and increases K+ excretion (out) by increasing expression and activity of the Na,K- ATPase in the renal tubule cells
(1) Increases H+ excretion (out) by the kidney
(2) Increases blood pressure by increasing plasma volume:
Increases water retention (osmotic reabsorption). This effect is secondary to Na+ retention and expansion of the extracellular fluid volume

Front 27

What are examples of synthetic glucocorticoids?

Back 27

Prednisone, Methylprednisone, Dexamethasone (listed in increasing potentcy)

Front 28

What are the negative side effects of administering glucocorticoids?

Back 28

Suppresses endogenous secretion of CRH, ACTH, and cortisol

High doses of cortisol for extended time (5-7 days) cause Cushing syndrome

Front 29

What are causes of adrenal cortex?

Back 29

Hypersecretion of adrenal cortex
Abnormally and chronically high level of cortisol
Caused by
Adenomas of the anterior pituitary that secrete large amounts of ACTH (Cushing’s disease)
Abnormal function of the hypothalamus that causes high levels of CRH
Ectopic secretion of ACTH
Adenomas of the adrenal cortex

Front 30

What are the characteristic findings of Cushing's syndrome/disease?

Back 30

Increased blood glucose (2x normal)
^increased gluconeogenesis & decreased glucose utilization
Decreased tissue proteins
^except liver & plasma
^severe weakness, immunosuppresion, purple striae, osteoporosis
Mobilization and redistribution of fat
^buffalo torso
Excess steroids
^edematous ("moon face"), acne, hirsutism
Excess mineralocortoids
^hypertension

Physical findings:
Fat pads, pendulous abdomen, striae, moon face, red cheeks, ecchymoses, thin skin, poor muscle development, poor wound healing.

Front 31

What is an example of primary hypoaldosteronism?

Back 31

Adrenal destruction,
Addison's disease

These patients clinically present with hyponatremia, hyperkalemia, mild acidemia, hypotension

Treat with mineralcorticoids and NaCl

Front 32

What is an example of primary hyperaldosteronism?

Back 32

Adenoma,
Conn's Disease

These pts clinically present with hypernatremia, hypokalemia, mild alkalosis, and hypertension

Treat with adenoma removal, adrenalectomy

Front 33

What is 21-hydroxylase deficiency

Back 33

An adrenogenital syndrome.

21- Hydroxylase deficiency is the most common enzymatic disorder that account for this syndrome
Adrenal androgens are produced in great excess, causing virilization
Production of cortisol is low
ACTH secretion is increased because the low cortisol production
Clinically: in females, ambiguous genitalia can lead to incorrect gender assignment at birth

Front 34

How are catecholamines synthesized?

Back 34

1.Tyrosine

2. DOPA

3. DOPAMINE
(goes into granules then becomes NE)
4. Norepinephrine (NE)

5. Epinephrine (EPI)

Front 35

How are catecholamines secreted?

Back 35

Secretion is initiated by acetylcholine (Ach) released from the preganglionic axons:
Ach → the membrane depolarization → an influx of Ca2+ → exocytosis of vesicles

Secretion can be stimulated by exercise, hypoglycemia, hemorrhage, and emotional stress

Front 36

Does the adrenal medulla secrete a higher proportion of NE or EPI?

At rest, does NE or EPI have the greater plasma concentration?

Back 36

85% EPI

NE, it is 2.8x greater than EPI

Front 37

What are the actions of the following adrenergic receptors?

alpha1
alpha 2
beta 1
beta2

Back 37

Alpha1: Calcium

Alpha 2: Decrease adenylyl cyclase, decrease cAMP

Beta1: increase AC, increase cAMP. Opens L type calcium channels in the heart

Beta 2 - increase AC, increase cAMP

Front 38

What are the physiological effects of medullary hormones?

Back 38

Increased rate and force of contraction of the heart muscle (beta 1)

Constriction of blood vessels (alpha 2)

Dilation of bronchioles (beta 2)

Stimulation of lipolysis

Increased metabolic rate

Breakdown glycogen

Dilation of the pupils

Inhibition of certain"non essential" processes

Front 39

Explain the mechanism of hyperglycemia in diabetes (w/ low insulin)

Back 39

low GLUT-4 uptake of glucose
high hepatic output of glucose

Front 40

What will happen if a person with normal thyroid hormone levels supplements with additional T3?

Back 40

serum T4 will drop
(neg feedback)

Front 41

3 types of corticosteroids

Back 41

mineralocorticoids
glucocorticoids
androgens

Front 42

What is the primary glucocorticoid and what does it regulate?

where are they primarily secreted?

Back 42

cortisol
metabolism of carbohydrates and anti-inflammatory response

secreted in target tissues (liver, adipose, kidneys, skin)

Front 43

What are the primary androgens and what do they do?

Back 43

Androstenedione & Dehydroepiandroesterone (DHEA)

-anabolic hormones, protein anabolism & growth, exert masculinizing effects
-converted into sex hormones in peripheral tissues, source of testosterone in women and estrogen in men

Front 44

Stress coping role of cortisol:
Stressor leads to increased (a)
increased (a) leads to increased (b)

Back 44

a. ACTH
b. glucocorticoids

Front 45

increased glucocorticoids stimulate what 4 things?
loss of glucocorticoids leads to what?

Back 45

1. Energy metabolism
2. Permissive for catecholamines & glucagon
3. Anti-inflammatory response
4. Emotions

leads to death

Front 46

Cortisol indirectly exerts calorigenic effects via ______ and ________
as well as lipolytic effects, vascoconstriction, & bronchodilation via _________

Back 46

calorigenic via glucagon and catecholamines

lipolytic, vasoconstriction, & bronchodilatiob via catecholamines

Front 47

Cortisol's effect on
Cardiovascular system-
Blood-
Connective tissue-
Kidney-

Back 47

Cardiovascular- permissive actions of catecholamine
Blood- stimulates erythropoietin synthesis
CT- inhibits fibroblast proliferation & collagen synthesis
Kidney- increases glomerular filtration rate (GFR)
indirectly by increasing cardiac output and directly by decreasing the release and activity of antidiuretic hormone (ADH)

Front 48

Most of Cushing's syndrome cases are _________.
They result from prolonged use of exogenous glucocorticoids

Back 48

Iatrogenic!!!

Front 49

Catecholamines are inactivated by tissue uptake and enzymatic degradation, then excreted in urine.
what 2 enzymes degrade them?

Back 49

monoamine oxidase (MAO), intracellular

catechol-O-methyltransferase (COMT), extracellular

Front 50

What hormone makes you cry (direct affect on lacrimal gland stimulates tears)?

Back 50

ACTH

Front 51

How is cortisol stored in the body?

Back 51

In circulation bound to plasma protein

Front 52

How does inactivation of MAO affect responses to norepinephrine?

Back 52

MAO inhibitors increase responses to norepinephrine

Front 53

T/F
Chocolate improves moods

Back 53

TRUE
contains MAO inhibitors, increases norepinephrine, increasing circulation and CNS, increasing mood