Physiology - Pancreas, Hypothyroidism

Front 1

What are the cells of the pancreas that act as exocrine, and what is the function? How about for endocrine

Back 1

Exocrine: neutralizing acidic gastric contents, digesting intraluminal carbs, fats and proteins; released by acinar cells.
Endocrine: secretes insulin and glucagon; released by Islets of Langerhans

Front 2

What 4 types of cells are inside the Islet of Langerhans, where are they, and what do they release?

Back 2

Alpha cells located near periphery, produces glucagon.
Beta cells located in center, produces insulin & amylin.
Delta cells located between beta cells and surrounding mantle of alpha cells, produces somatostatin.
F-cells is least abundant cell, has delta-cell like distribution, and produces pancreatic polypeptide.
Note that blood flows from the center to the periphery

Front 3

What are 3 functions of glucagon?

Back 3

Principal target tissue is the liver
Main actions involve carbohydrate and lipid metabolism
Glycogenolysis, gluconeogenesis, ketogenesis

Front 4

What are 3 functions of amylin?

Back 4

Co-secreted with insulin
Suppresses glucagon secretion, and prevents hepatic production of glucose
Slows intestinal absorption

Front 5

What are 2 functions of somatostatin?

Back 5

Inhibits secretion of several hormones (e.g. insulin, glucagon, thyroid stimulating hormone)
As blood flows from centrally localized beta cells to peripherally localized alpha cells, an endocrine effect is minimized, yet paracrine effects may exist

Front 6

What are 3 functions of pancreatic polypeptide?

Back 6

Reduces gastric emptying, slowing absorption of food
Decreases upper insteinal motility
Inhibits exocrine pancreas secretion

Front 7

What is the main regulator of insulin secretion? How does it work?

Back 7

Glucose is main regulator of insulin secretion. Modest increases in plasma glucose causes marked increase in insulin. A decline in plasma glucose only lowers insulin by 20% or so.

Metabolism of glucose triggers insulin secretion:
1) Glucose enters beta-cell via GLUT
2) increased glucose influx stimulates glucose metabolism, leading to an increase in ATP
3) Increased ATP inhibits an ATP sensitive channel
4) Inhibition of K+ channel causes membrane to depolarize
5) Depolarization activates a voltage-gated Ca2+ channel in plasma membrane, increasing Ca2+ influx and intracellular Ca2+
6) Increased in Ca2+ leads to exocytosis & release of insulin contained within secretory granules

Front 8

How does sympathetics and parasympathetics modulate insulin secretion - and at what conditions do these occur? What about enteric factors?

Back 8

Beta-adrenergic stimulation increases insulin secretion; alpha adrenergic stimulation decreases insulin secretion. Exercise inhbits insulin secretion, as sympathetic neurons release NE that stimulates more alpha than beta.
Acetylcholine causes an increase in insulin secretion; occurs during the cephalic phase, which is mediated by AcH release from the vagus nerves
CCK, GIP, GLP-1 are released by gut tissues in response to feeding, and can enhance insulin secretion.

Front 9

What are the 3 organs of action for the liver, and what are some of the activities there?

Back 9

Liver: Increase glycogen synthesis, protein synthesis, lipid synthesis. Decrease gluconeogensis and ketogenesis

Skeletal muscle: Increase glucose uptake, glycogen synthesis, amino acid uptake, protein synthesis, potassium uptake. Decrease in protein catabolism and release of gluconeogenic amino acids.

Increase glucose uptake, fatty acid synthesis, glycerol phosphate synthesis, TAG deposition, potassium uptake. Decreases hormone-sensitive lipase, but ACTIVATES LIPOPROTEIN LIPASE.

Front 10

Describe the intracellular signaling network in insulin on muscle and fat cells.

Back 10

Two insulin cascades have been described, that stimulate the redistribution of glucose transporter GLUT4 from intracellular vesicle membranes to plasma membrane. One of the pathways is IRS -> PI3K -> Akt-2 -> AS160, whereas the other is ABS/Cbl/TC10 cascade.

Other insulin signaling cascades mediate growth & gene expression, protien synthesis, anti-apoptosis, anti-lipolysis, and glycogen synthesis.

Front 11

Describe the difference between Type 1 and Type 2/Gestational/Prediabetes.

Back 11

Type 1 Diabetes: Caused by autoimmune destruction of pancreatic beta cells. Note that when c-peptide shows up, will be pretty bad. Diagnosed in children and young adults (previous known as juvenile diabetes).
Type 2 Diabetse: Insulin resistance, with a lower than normal response to a given concentration of insulin. Contributed by the insulin signaling defects contribute to this; hyperinsulinemia, hyperglycemia, and hyperlipidemia worsen insulin sensitivty and cardiovascular function, resulting in METABOLIC SYNDROME

Front 12

Describe the numbers you would get for non-diabetic, pre-diabetic, and diabetic people taking the Fasting Plasma glucose test (FPG) or the Oral Glucose Tolerance Test (OGTT).

Back 12

Nondiabetic - FPG < 99mg/dL; OGTT <139mg/dL
Pre-diabetic - FPG = 100-125mg/dL; OGTT = 140 - 199mg/dL
FPG: >126mg/dL; OGTT >200mg/dL

Front 13

What is the molecular pathogenesis of insulin resistance?

Back 13

Naturally occuring mutations in the insulin receptors are rare, normally seen in syndrome of extreme insulin resistance, such as Leprechaunism. Receptor defects are not a major basis of insulin resistance.

In Metabolic Syndrome, accumulating data suggsts that glucose, lipids, and even insulin itself will woren insulin sensitivity and lesions in the circulatory system, kidneys and nervous system. Chronic complications include circulatory system lesions, renal failure, neuropathy.

Front 14

Name three components of lifestyle intervention for diabetse

Back 14

Self-management education, nutritional counseling, and exercise recommendations

Front 15

Name the actions of these 8 diabetic drugs: Sulfonylurea, Biguanide, Thiazolidnedione Meglitinide, Alpha-glucose inhibitor, Incretin hormones/GLP-1, Nateglinide, DPPIV inhibitors

Back 15

Sulfonylurea: stimulates beta cells to release more insulin
Meglitinide: works with similar action to sulfonylureas
Nateglinide: works with similar action to sulfonylureas
Biguanide: sensitizes the body to the insulin already present to liver
Thiazolidinedione: helps insulin work better in muscle and fat; lowers insulin resistance;
Alpha-Glucose inhibitor: slows or blocks the breakdown of starches and certain sugars; action slows the rise in blood sugar levels following a meal;
Analogus of incretin hormones: modulates hepatic glucose production and in the post prandial state to regulate glucose clearance.
Enzyme inhibitors of dipeptidyl peptidase IV (DPPIV)

Front 16

What are symptoms of hypothyroidism (and yet, won't be seen in subclinical hypothyroidism)?

Back 16

Hair loss (lateral eyebrows), periorbital swelling, peripheral edema, yellowish skin pigmentation

Front 17

What are molecular activities that can go wrong in thyroid hormone synthesis (5 of them)?

Back 17

TSH receptor; Na:I Symporter; Pendrin (another iodide transporter on colloid side); thyroglubulin synthesis; thyroperoxidase (TPO)

Front 18

How are TSH, T3 and T4levels like in subclinical hypothyroidism? Hypothyroidism? Euthyroidism? Hyperthyroidism? Hypopituitarism? TSH producing pituitary hormones?

Back 18

Subclinical hypothyroidism: suboptimal T3 and T4, high TSH
Hypothyroidism: low T3 and T4, high TSH
Hyperthyroidism: high T3 and T4, low TSH
Euthryoidism: normal;
Hypopituitarism: low T3, T4; TSH relatively normal
TSH producing pituitary hormones: high TSH, high T3 and T4

Front 19

How does hypothyroidism prevelance change with age and sex?

Back 19

Increases with age, more common in females than males

Front 20

What are 2 important factors that can predict hypothyroidism?

Back 20

TSH, and presence of TPO Antibodies

Front 21

What are 4 mechanisms of pathophysiology in hypothyroidism?

Back 21

Hyperlipidemia, cardiovascular disease (increased artherosclerotic risk), cardiac function (decreased contractility), and neurophysiologic symptoms

Front 22

Name a few symptoms of hypothyroidism.

Back 22

Hoarse voice, deep voice, DRY SKIN, COLD INTOLERANCE, fatigue, puffy eyes, muscle cramps, constipation, slow thinking, poor memory.

Front 23

Any effects of maternal hypothyroidism on maternal offspring?

Back 23

Decrease in IQ; increased incidence of neonatal death

Front 24

What do you use to find tune hypothyroidism therapy?

Back 24

Use TSH levels, such that it is in optimal range.

Front 25

Name 4 mechanisms for hypothyroidism drugs to increase T4 dose

Back 25

Reduce GI T4 absorption; increase T4 degradation; reduce T4 to T3 conversion; increase thyroxine binding globulin