Endocrine System Physiology 2 - Teel

Question 1

Effects of Aldosterone on Target Epithelial Cells

Mechanism

Answer 1

Aldosterone binds to receptor
Complex acts on nucleus, triggers mRNA synthesis / protein synthesis
Causes action on Na K pump, ENac channels.
ENac on lumen, Na K on interstitial side.

Question 2

Actions of Aldosterone

modulates…
stimulates secretion of…
stimulates reabsorption of…

Answer 2

Modulates transcription of Na-K transporters, ENAC channels and Na-K-2Cl cotransporters in target cells.

Stimulate secretion of K+ by principal cells of cortical collecting tubules of kidney

Stimulate reabsorption of Na+ in renal distal tubules and collecting ducts resulting in increased ECF volume and increased blood pressure

Question 3

Synthesis of Androgens

Answer 3

Zona reticularis

Begins with cholesterol. Still need cytochrome p450 (CYP 450).

Confined to mitochondria in some cases, ER in others.

Question 4

Synthesis of Aldosterone

Answer 4

Zona Glomerulosa

Synthesize aldosterone from cholesterol.

Several CYP 450 enzymes involved

Question 5

Synthesis and secretion of Cortisol

Answer 5

Zona Fasciculata

Start with Cholesterol.

Several CYP 450 involved.

Question 6

Hypothalamic-anterior pituitary-adrenal axis

Stimulation of Paraventricular nuclei of hypothalamus cause release of CRH. What happens after?

Answer 6

1.)Release of CRH.
2.)CRH binds to receptors in Corticotroph cells in Ant. Pit., stimulate secretion of ACTH. 3.) ACTH in plasma binds to receptors in cells of adrenal cortex which stimulate secretion of cortisol.

Note: Negative feedback occurs

Question 7

Diurnal secretion patterns:

Answer 7

ACTH / Cortisol exhibit pulsatile and diurnal secretion patterns.

Cortisol has a big jump at 8 am (assuming u have normal sleep pattern) This is the diurnal peak.

Question 8

Actions of Cortisol:

Answer 8

Main: tends to elevate blood glucose levels. Therefore, stimulate gluconeogenesis/glycogenolysis.

Stimulate protein catabolism in muscle
Mobilize fat from subcutaneous adipose tissue
Diabetogenic**
Anti-inflammatory
Suppress immune function
Inhibit osteoblasts and stimulates osteoclasts in bone.*

Important: cortisol is diabetogenic (insulin antagonist, raising blood glucose)

Question 9

Mechanism of Cortisol:

Answer 9

Cortisol binds to cytoplasmic receptor, translocates to nucleus of target cells to enhance / depress GENE expression.

Question 10

Anti-inflammatory Actions of Cortisol:

Answer 10

Cortisol inhibits phospholipase A2

This enzyme triggers release of inflammatory mediators.

Stabilizes lysosomal membranes thus minimizing release of proteolytic agents. (If lysosomes are released, then proteolytic effects occur which are inflammatory)

Question 11

Adrenal Medulla, Actions of Catecholamines

Answer 11

Effects include fight or flight responses
Most tissues have either a or B receptors for catecholamines

Question 12

Addison’s disease

Answer 12

This is an adrenal dysfunction, adrenal insufficiency disease

Symptoms:
Skin hyperpigmentation
Hypoglycemia
Impaired gluconeogenesis
Increased sensitivity to insulin
Hypotension
Increased free water clearance
Anorexia, nausea, vomiting, diarrhea
Mental confusion
Decrease sensitivity to catecholamines

Question 13

“Might see a quiz question on free water clearance”

Answer 13

“Water in urine, free of solute”. The more free water clearance you have, the more dilute your urine is.

Question 14

Cushing’s Disease

Answer 14

Adrenal Dysfunction, too much cortisol being produced. Hypercortisolism.

Symptoms:
Hyperglycemia
Centripedal fat distribution (buffalo hump, pads in shoulder region)
Loss of tissue from arms, legs
Elevated blood glucose
Thickness of skin compromised, thus bruises occur

Moon Face

Question 15

Anti-inflammatory actions of cortisol

Answer 15

Stabilizes lysosomal membranes
Decrease capillary permeability, affects leukocytes
Suppress T-cell activity
Modulates fever by inhibiting release of interleukin-1 (suppress fever)

(affects the things that help fight off infection)

Question 16

The Endocrine Pancreas

Islets of Langerhans Cell Types:

Answer 16

a -> glucagons
B -> insulin, proinsulin, C-peptide and amylin
omega -> somatostatin
F -> pancreatic polypeptide

Question 17

Problems with diabetics:

Answer 17

Blood glucose level much higher
Fasting level is elevated
not much response of insulin in body from an oral dose of glucose

Question 18

Where are glucose transporters located?

Answer 18

Kidney and GI tract

Question 19

Uptake of glucose due to a rise in blood sugar will trigger…

Mechanism

Answer 19

1.) blood glucose levels rise
2.) activity of GLUT 2 transporter of B-cell occurs. Takes up glucose
3.) Generates ATP and closing of potassium channel -> depolarization
4.) Depolarization opens calcium channel (Ca+ is second messenger)
5.) Insulin released into bloodstream (via proinsulin, C-peptide, pre-formed granules)

Uptake of glucose due to a rise in blood sugar will trigger uptake of glucose by beta cell

Question 20

Target cell of insulin:

Mechanism

Answer 20

1.) Binding of Insulin on insulin receptors (GLUT 4)of target cell membranes
2.) Cause uptake of glucose into tissue / into cell
3.) Can cause protein synthesis, fat synthesis, glycogen synthesis, growth, etc.

Question 21

Difference between cortisol / insulin

Answer 21

Cortisol: Catabolic. Inhibiting pathway, breakdown of things
Insulin: Anabolic. Synthesis of things

Cortisol is an insulin antagonist (and glucagon). Pretty much does opposite of what insulin does.

Question 22

Actions of insulin on Muscle, Adipocytes, Liver, Growth:

Answer 22

Muscle: Stimulates glucose -> glycogen
Adipocytes: Glucose -> triglycerides
Liver: glucose -> glycogen. Inhibits gluconeogensis
Growth: Transcription / translation, promotes AA uptake into cells. Works synergistically with growth hormone and inhibits gluconeogenesis and catabolism of protein.

Question 23

Glucagon secreted by…

Answer 23

a-cells of islets of langerhans

Question 24

Actions of glucagon:

Answer 24

ketogenesis (oxidation of lipids in liver)
Stimulates gluconeogenesis / lipolysis in non-hepatic tissue
Hepatocytes: Glycogenolysis. release of glucose.

Question 25

Confusing…:

Insulin antagonists:

Answer 25

Insulin antagonists:

Glucagon
Cortisol
Epinephrine
Growth Hormone

Stimulus for growth hormone is low blood sugar, and u get elevated blood sugar as a response. Thus it is an insulin antagonist.

However, Insulin and growth hormone work together in growth.

Question 26

Control of blood glucose:

Fed state vs Fasting state

Answer 26

Fed state: Insulin increase, glucagon decrease -> glycogenesis, increased FFA uptake, lipogenesis, increase protein synthesis, decrease glucose, decrease FFA and AA in systemic circulation

Fasting state: opposite. glycogenolysis, gluconeogenesis, lipolysis, ketogenesis

Question 27

Effects of hypoglycemia / hyperglycemia

Answer 27

Hypoglycemia (low blood sugar): sweating, tachycardia, palor following sympathetic discharge with blood glucose < 50 mg/dl. Shud be around 70-80.

Hyperglycemia (high blood sugar): ketoacidosis can result in coma and death

Question 28

Type I vs Type II diabetes

Answer 28

Type I:
5-10% of US
autoimmune
usually before age 20
Requires exogenous insulin (insulin injection)

Type II:
90-95% of US
usually after 40
linked to metabolic syndrome
defects in insulin secretion or response to insulin.