Endocrine 3

Question 1

What are the causes of stress? What are the hormones?

Answer 1

Stress:
-trauma

• exposure to cold
• illness
• starvation
• exercise

Stress hormones usually act to mobilize energy stores. The stress hormones are:
-growth hormone

• glucagon
• cortisol
• epinephrine

Note: all stress hormones raise plasma glucose

Question 2

What are the metabolic actions of cortisol ?

Answer 2

Cortisol promotes mobilization of energy stores, specifically

1. Protein —> promotes degradation and increased delivery of hepatic gluconeogenic precursors
2. Lipid—> promotes lypolysis and increased free fatty acids & glycerol
3. Carbohydrate—> increase hepatic output of glucose by inducing the enzymes involved in gluconeogenesis

Note: Cortisol has permissive action which enhances the capacity of glucagon and Catecholamines (epinephrine, norepinephrine)

Question 3

Explain cortisol regulation

Answer 3

Corticotropin releasing hormone(CRH) secretion increases in response to stress and early morning

-ACTH stimulates the secretion of cortisol (and adrenal androgens) of the adrenal cortex

Note: Cortisol suppress the release of the ACTH by acting on the hypothalamus and anterior pituitary

Question 4

What stimulates cortisol regulation ?

Answer 4

1. stress and time of day input from Supra chiasmatic nucleus(SCN) - CRH peaks early morning and low early evening
2. Anterior pituitary corticotrophs synthesize Pro-opiomelanvocortin forms ACTH(stimulates cortisol) and B-lipotropin(forms B-MSH and endorphins sh8ch modulate pain)

Question 5

Explain aldosterone physiologic action

Answer 5

• luminal membrane contains sodium channels (eNaC). These channels allow for influx of sodium down its concentration gradient (created by Na/K+-ATPase)
• Some chloride doesn’t follow sodium, creating a negative luminal potential causing potassium secretion
• Aldosterone activates the mineralocorticoid receptor on these cells, having the following effects:
  1. Increasing luminal ENaC channels
  2. Increase ENaC opening time
  3. Stimulates/Augments Na/K+-ATPase

Question 6

How can physiologic action of aldosterone lead to metabolic alkalosis?

Answer 6

Luminal membrane contains a H+-ATPase, which pumps H+ into the lumen

• Most of the H+ is eliminated from the body via buffers, phosphate and ammonia
• H+ pumped into the lumen binds to phosphate, which is poorly reabsorbed, thus eliminating H+
• H+ can combine with ammonia to form ammonium, which is poorly reabsorbed is thus excreted
• For every H+ excreted by the above buffers, bicarbonate is added to the body (new bicarbonate)
• Aldosterone stimulates H+-ATPase of intercalated cells. Thus, excess aldosterone causes metabolic alkalosis

Question 7

How is aldosterone regulated?

Answer 7

The major rebulators of aldosterone are

-Angiotensin II.

-High potassium (hyperkalemia)
These stimulate zona glomerulosa of adrenal cortex to release aldosterone

Angiotensin II can be increased by any stimulus that causes renin release

1. Hypovolemia (hemorrhage)
2. Decrease sodium delivery to macula densa
3. Sympathetic (via B-1 receptors) input to Juxtaglomerular cells)

Question 8

What are adrenal androgens?

Answer 8

The major secreted form is dehydroepiandrosterone(DHEA)

-DHEA, DHEA sulphate and androstenedione have very low andronergic activity. They function primarily as precursors for the conversion to more potent testosterone and dihydrotestosterone

Question 9

What is epinephrine?

Answer 9

Liver—> promotes glycogenolysis (break down glycogen too glucose). Increases glucose output by liver

Skeletal muscle—> promotes glycogenolysis but no glucose release( muscle lacks the enzyme to break it down all the way down to gluc9se)

Adipose —> increase lipolysis, releasing glycerol, a substrate for gluconeogenesis

Question 10

Describe the control of insulin release

Answer 10

Most important controller of insulin secretion is plasma glucose. Above a threshold of 100 mg, insulin secretion is directly proportional to plasma glucose

• Glucose enters the cell, causing a rise in intracellular ATP that closes ATP sensitive K+ channels
• Closure of the ATP-sensitive K+ channels results in depolarization causing voltage gated Ca2+ channel to open
• Rise in intracellular Ca2+ causes exocytosis of the vesicles containing insulin and C-peptide

Question 11

What are the cellular actions of insulin on carb metabolism ?

Answer 11

Insulin increases the uptake of glucose and its metabolism in muscle and fat

• Skeletal muscle and adipose tissue have GLUT-4 (glucose transporter)
• The rate of glucose transport in these two tissues is INCREASED by insulin which stimulates the movement of additional GLUT- 4 transporters to th3 membrane
• Insulin increases glycogen synthesis in the liver and muscle
• The activity of the enzymes that promote glycogen synthesis (Glucokinase & glycogen synthase) is increased

Question 12

What are the cellular actions of insulin on protein metabolism?

Answer 12

Insulin increases amino acids uptake by muscles cells

• Insulin increases protein synthesis
• Insulin decreases protein breakdown (deficiency of insulin causes breakdown of protein)

Question 13

What are the cellular actions of insulin on lipid metabolism?

Answer 13

By increasing glucose uptake, insulin also promotes triose phosphate available for triglyceride synthesis

• Increases the activity of lipoprotein lipase. Lipoprotein lipase causes the release of free fatty acids from triglycerides
• Triglyceride synthesis (lipogenesis) is increased by insulin stimulating the Acetyl-CoA carboxylase

Question 14

Summarize cellular action of insulin

Answer 14

-insulin promotes K+ movement into the cells. Although the overall action isn’t well understood, insulin increases the activity of Na/K+-ATPase in most body tissue

Note: When a patient develops hyperkalemia (excess potassium in the blood), insulin and glucose is normally given to reduce the blood level of potassium

Question 15

Describe pancreas control release of glucagon

Answer 15

Low blood glucose (hypoglycemia) is the most important physiologic promoter for glucagon secretion and hyperglycemia is the most important inhibitor

Amino acids especially dibasic amino acids such as arginine, also promotes the secretion of glucagon

Note: glucagon is secreted in response to the ingestion of a meal rich in protein

Question 16

What are the effects of cellular glucagon?

Answer 16

• increase liver glycogenesis
• increase liver gluconeogenesis
• increases liver ketogenesis and decrease lipogenesis
• increase urease
• increase insulin secretion
• increase lipolysis in the liver

Question 17

What happens in the fed state ?

Answer 17

Anabolic

Increased glucose oxidation

Increase glycogen synthesis

Increase fat synthesis

Increase protein synthesis

Question 18

What happens in the fasted state?

Answer 18

Glucagon dominates

Increased gluconeogenesis

Increased ketogenesis

Increased glycogenolysis