What are the important hormones secreted by the pancreas?

What else does the pancreas assist with?

What are the 2 types of tissue cells in the pancreas, and what do they do?

Insulin, glucagon, and somatostatin.  There are others, including pancreatic polypeptide and amylin, but the function of these is not well understood.

The digestive function.

Acini cells, which secrete digestive juices into the duodenum.

Islets of Langerhans, which secrete insulin and glucagon into the blood.

1-2 million islets of Langerhans, which are organized around small capillaries.  The islets contain 4 types of cells.

1.  Alpha cells secrete glucagon

2.  Beta cells (largest in number) secrete insulin

3.  Delta cells secrete somatostatin

4.  PP cells secrete pancreatic polypeptide

What do insulin and glucagon do, and what controls their secretion?

What does somatostatin do?

What range are blood sugar levels maintained at normally?

Crucial role in regulating carbohydrate, fat, and protein metabolism.  Secretion is based on periods of feast and famine throughout the day.

Plays a role in regulating GI function by restraining the rate at which nutrients are digested and absorbed.  Also plays a role in inhibiting growth hormone release.

90-140 mg/dl

Describe the structure of insulin.

Describe the process of insulin production.

A small protein that is comprised of 2 amino acid chains (alpha and beta) connected by disulfate linkages.

Initially, insulin is translated as a preprohormone by the ribosome.  The endoplasmic reticulum cleaves it into the prohormone.  The golgi apparatus further cleaves it to insulin, and stores it.  (Golgi also stores some prohormone, but this is not functional to the tissues--must be cleaved before release).

How is insulin released into the blood?

What is the half-life of circulating insulin?

When is it cleared from the plasma, and what does this?

Unbound, which allows it to be able to go to work immediately.

Plasma half life is 6 minutes.

Cleared from the plasma between 10-15 minutes by insulinase in the liver.

What are the parts of the insulin receptor?

What happens to the receptor when insulin binds?

Two alpha subunits outside the cell, and two beta subunits inside the cell.

When insulin binds to the alpha subunits, there is a change in the beta subunit which produces phosphorylation of tyrosine kinase, which promotes several enzyme reactions.

1.  Cells increase the uptake of glucose, especially in the muscle and adipose.

2.  Increased cell utilization of glucose, sparing the use of fat as energy.

3.  Cells become more permeable to amino acid transport into the cell, inhibiting the breakdown of proteins.

4.  Insulin impacts ion transport (Na-K-ATPase pump)

5.  Many other enzyme reactions (metabolism)

6.  New protein formation

Unused glucose is stored as glycogen.  Insulin also increases the uptake of glucose in the liver, and is also stored as glycogen (glycogenesis).  

The does not occur in the brain and neuron tissue--with no stores, they need a constant supply of glucose. 

What happens when too many carbs are ingested?

What happens when there is not enough insulin?

If insulin causes cells to become more permeable to amino acid transport into the cell, what is the result?

What does an increase in plasma glucose result in?

What other factors increase insulin release?

Insulin favors the formation of new proteins and muscle growth.

A biphasic release of insulin.  The first release happens quickly--3-5 minutes.  The second occurs in 15 minutes and is sustained for 2 hours.

An increase in amino acid presence, gastrin, secretin, and cholesystokinin, gastric inhibitory peptide, growth hormone, cortisol, estrogen, progesterone, and glucagon.

How does epinephrin increase plasma glucose levels?

Where is glucagon secreted, and what is the action?

By stimulating the beta 2 agonist receptor on the liver and adipose tissue when the sympathetic nervous system is excited.

Secreted by alpha cells, acts opposite of insulin.

Causes glycogenolysis (breakdown of glycogen stores in liver), freeing glucose.  Frees fatty acids and inhibits the storage of triglycerides.  Acts as a positive inotrope.  It increases blood flow to the kidney, and inhibits gastric acid secretion.  It increases the blood sugar concentration.

Glycogen works in concert with what other hormones?

What inhibits the release of glucagon?

Why is glucagon used for beta blocker overdose?

What does somatostatin do?

Epinephrine, cortisol, and growth hormone.

Inhibited by the rise in blood glucose.

Glucagon acts as a positive inotrope, increasing cardiac contractility thru other mechanisms other than beta receptors.

Inhibits glucagon and insulin secretion.

What characterized diabetes mellitus?

What are the blood sugar levels?

Why is the incidence of diabetes on the rise?

What is Type I diabetes?

Impaired carbohydrate, fat, and protein metabolism due to a lack of insulin secretion or the inability of the cell to respond to insulin.

Fasting blood sugar > 125 mg/dl or random > 200.

Obesity, sedentary lifestyle, rise in the elderly population.

Insulin dependent--caused by a lack of insulin secretion.

What is thought to cause type I diabetes? 

When is the typical onset?  What are symptoms?

What is one treatment beginning to show promise?

Viral infection or autoimmune disorder that destroys the beta cells of the islet.  The susceptibility of these cells to destruction can be familial.  May be prone to other autoimmune disorders.

Typically occurs at age 14 and presents very abruptly.

Fatigue, weight loss, polyuria, polydipsia, intravascular volume depletion.  Ketoacidosis indicates sever insulin deficiency.

Pancreatic transplant.

What causes Type II diabetes?

What is the typical age of onset?

How long is the typical onset?

What are the first symptoms?

NIDDM, caused by a reduction in cell sensitivity to insulin--insulin resistance.  

Used to be associated with age, but d/t increasing childhood obesity, more people are being dx earlier.

Type II DM occurs gradually. 

Usually result in hyperinsulinemia as a compensation for high glucose levels.  Eventually, the pancreas burns out, and cannot produce enough insulin.  Patients must then transition from oral meds to insulin.

Metabolic syndrome, leading to:

obesity (belly fat)

hyperglycemia (fasting > 110 mg/dl)

lipid abnormalities (increased triglycerides, LDL, decreased HDL)

hypertension.

Polycystic ovarian syndrome

Glucocorticoids (Cushing's)

Steroid administration

Growth hormone (acromegaly)

What do the cells do when they can't get glucose in (insulin deficiency)?

What happens when protein stores are used?

What happens to many proteins?  Which one do we test?

They begin to use other energy sources, such as fat metabolism, leading to high triglyceride blood levels and increases circulating lipids.  This contributes to atheosclerotic and angiopathic changes.

This leads to muscle wasting and muscle fatigue.  This stimulates the appetite (polyphagia) in an attempt to replace amino acids.

Glucose laden, or saturated, including hemoglobin.  This is why we test Hbg A1C.

What is one complication of diabetes, often distributed through the body?  What are the two types?

What type of infection is common?  What extremity surgeries are common?

Arterial thrombotic lesions, distributed throughout the extremities, kidneys, eyes, muscle, myocardium, and nervous system.  Microvascular, including nephropathy, neuropathy, retinopathy.  Macrovascular, including atherosclerosis, stroke, and CAD.

Diabetics are 17X more likely to have gangrene.  Lower extremity vascular grafting or amputations are common.

What is the leading cause of diabetic-related death?

70% of diabetics have what circulatory condition?  What other risk is elevated?

What eye complication is more likely?

What about the kidneys?

What types of neuropathy do diabetics have?

What can occur early in the disease process?

Heart disease.  70% have hypertension.  Risk for stroke is 2-4X more.

Blindness is 25X more likely in diabetics.

Diabetes is the leading cause of ESRD

Peripheral and AUTONOMIC nervous system!!

Vagal denervation, which manifests as tachycardia, dysrhythmias, and loss of heart rate variability seen with deep breathing.

Why do diabetics get orthostatic hypotension?

Patients with autonomic neuropathy are at increased risk for what?  What is a sign?

Due to autonomic neuropathy as a result of a dysfunctional sympathetic nervous system that loses its vasoconstrictive capability.  Patients have postural syncope, dizziness, and lightheadedness.

Developing PAINLESS myocardial ischemia!!  Unexplained hypotension is a sign of a potential MI in these patients.

Why would we rapid sequence a diabetic?

What are some indicators they might be at risk?

What condition might complicate RSI?

If autonomic neuropathy exists, they may have delayed gastric emptying.

1.  How long have they been diabetic

2.  Insulin versus non-insulin DM

3.  Other autonomic neuropathy symptoms.

ESRD and potassium.

Are hormones made in the posterior pituitary?

What happens if the posterior pituitary is cut at the stalk?

Where is ADH primarily made?

Where is oxytocin primarily made?

Can they be made elsewhere?

No--they are made in the hypothalamus and stored in the posterior pituitary awaiting release.

The hormones will still be released at the point of the neuron where they are cut.

ADH is made in the supraoptic nuclei.

Oxytocin is made in the paraventricular nuclei.

Each of these nuclei can synthesize small amounts of the other hormone.

How are oxytocin and ADH similar?

What happens if oxytocin is given in large doses?

Where does ADH work?  How?

What controls the release?

They are structurally similar, with partial functional similarities.

Large amounts of oxytocin will act like ADH, causing water toxicity.

ADH works in the collecting tubules in the kidney, resulting in an increased number of aquaporins.

The osmolarity of the blood circulating around the hypothalamus (osmoreceptors) determines the release of ADH.

What is the difference in ADH and vasopressin?

What stimulates vasopressin release?

The concentration--minute doses affects the kidney, while larger doses causes vasoconstriction.

1.  Stretch receptors in the atria--less stretch = less volume, resulting in a release of ADH.

2.  Decrease baroreceptor response.

What sends the afferent signal from the baroreceptors, and where does the signal go?

What is the result of the efferent signal from the baroreceptor?

The carotid bodies sent a signal via Hering's nerve, a branch of the glossopharyngeal nerve, and the aortic arch sends a signal via the vagus nerve, to the tractus solitarius of the medulla.

The efferent signal is the excitation of the parasympathetic vagal centers and inhibition of the sympathetic nervous system leading to vasodilation of the peripheral vascular beds and negative chronotropy and inotropy.

What is diabetes insipidus?

What is it due to?

How can you tell which it is?

What are the manifestations?

Absence of vasopressin, due to

1.  Destruction of the posterior pituitary (neurogenic DI)

2.  Failure of the renal tubes to respond to ADH (nephrogenic DI)

If exogenous vaso works, it is neurogenic.

1.  Polydipsia

2.  Increased serum osmolarity

3.  Decreased urine osmolarity

4.  High urine output

What is SIADH?

What causes it?

What are the manifestations?

Too much ADH, as a result of tumors, hypothyroidism, porphyria, and small cell carcinomas, as well as general anesthesia.

1.  Decreased serum osmolarity

2.  Hyponatremia

3.  Increased urine osmolarity

4.  Symptoms are often associated with hyponatremia

When does hyponatremia cause confusion?

EKG changes?

Seizures?

Na < 120 = confusion

Na < 115 = QRS widening

Na < 102 = seizures, coma, death.