Endocrine 3 Flashcards
What are the causes of stress? What are the hormones?
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
What are the metabolic actions of cortisol ?
Cortisol promotes mobilization of energy stores, specifically
- Protein —> promotes degradation and increased delivery of hepatic gluconeogenic precursors
- Lipid—> promotes lypolysis and increased free fatty acids & glycerol
- 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)
Explain cortisol regulation
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
What stimulates cortisol regulation ?
- stress and time of day input from Supra chiasmatic nucleus(SCN) - CRH peaks early morning and low early evening
- Anterior pituitary corticotrophs synthesize Pro-opiomelanvocortin forms ACTH(stimulates cortisol) and B-lipotropin(forms B-MSH and endorphins sh8ch modulate pain)
Explain aldosterone physiologic action
- 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
How can physiologic action of aldosterone lead to metabolic alkalosis?
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
How is aldosterone regulated?
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
- Hypovolemia (hemorrhage)
- Decrease sodium delivery to macula densa
- Sympathetic (via B-1 receptors) input to Juxtaglomerular cells)
What are adrenal androgens?
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
What is epinephrine?
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
Describe the control of insulin release
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
What are the cellular actions of insulin on carb metabolism ?
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
What are the cellular actions of insulin on protein metabolism?
Insulin increases amino acids uptake by muscles cells
- Insulin increases protein synthesis
- Insulin decreases protein breakdown (deficiency of insulin causes breakdown of protein)
What are the cellular actions of insulin on lipid metabolism?
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
Summarize cellular action of insulin
-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
Describe pancreas control release of glucagon
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
