Unit 9

Front 1

1. Identify the five different functions of the endocrine system p655

Back 1

The endocrine system has diverse functions, including sexual differentiation, growth and development, and continuous maintenance of the body’s internal environment.

Front 2

2. Describe the general characteristics of hormones p655

Back 2

Hormones are chemical messangers synthesized by endocrine glands and released into circulation. Have specific negative and positive feedback mechanisms. Most hormone levels are regulated by negative feedback, in which tropic hormone secfetion raises the level of specific hormone, which feeds back causing secretion of the tropic hormone to subside.

Front 3

3. Discuss the negative feedback loop in relation to regulation of hormonal secretion 655

Back 3

Negative Feedback System
1. Purpose
2. Compare the negative feedback system to the thermostat in your house. You have it turned to a temperature that is comfortable for you. When that level is reached, the thermostat turns off. When the temperature becomes less than what has been set, the thermostat turns back on.
3. Example - there are low levels of circulating hormones in our blood. So, if the hypothalamus senses a low circulating level of T4, it secretes a releasing hormone that than acts on the pituitary gland that responds by releasing a tropic hormone that acts on the thyroid to secrete more T4. When the level of T4 is restored, the secretion of the hormones from "above" get turned off, thus the thyroid gland is turned off as well.

Front 4

4. Diagram the relationship between the hypothalamus and the pituitary, the hormones secreted by each, and the effect on the target organs. P661

Back 4

The pituttary gland, consisting of anterior and posterior portions, is connected to the central nervous system through the hypothalamus. Hypothalamus regulates anterior pituitary function by secreting releasing hormones into the portal circulation.

Front 5

5. Describe the link between first and second messengers and the transport of water soluble hormones p658

Back 5

Water soluble hormones act as first messengers, binding to recepotors on the cell’s plasma membrane. The signals initiated by hormone receptor binding are then transmitted into the cell by the action fo second messengers. Second messengers that have been identified include cAMP, cGMP, and calcium which associates with inositol triphosphatase, and diacylglcerol to produce physiologic effects. The First and Second Messenger System
1. The water-soluble hormone bound to the plasma membrane receptor acts as the first messenger.
2. There are several second messengers. Their role is to act as a link between the first messenger and the inside of the cell, so the cell can than respond to the hormone.
3. Compare this to an answering machine system. The first message is the call (hormone) which is received by the answering machine (cell membrane receptor). The recording of the message on the tape is the second messenger (cAMP or calcium for example), which then gives directions to the recipient (cell). The recipient (cell) gets the message from the answering machine and carries out the message. For example, your child calls (hormone) and leaves a message that he needs to be picked up after school on the answering machine (receptor on the cell membrane). The tape then relays the message that gives that direction, and then the recipient (cell) acts as instructed.

Front 6

6. Discuss the similarities and differences among the thyroid hormones and calcitonin p658

Back 6

A. Role of Follicular Cells
1. Three functions
a. Collect and transport iodine
b. Synthesize thyroglobulin (a glycoprotein that does not contain iodine but does contain tyrosine amino acids) and secrete it into the colloid (a jelly like substance that fills the follicle. It is in the colloid that T3 and T4 are synthesized by iodination and condensation of tyrosine of the thyroglobulin)
c. Remove the hormones from thyroglobulin and secrete them into the circulation. After the hormones get into the circulation, they are bound to proteins (albumin mostly).
B. The Role of Parafollicular cells (C cells)
1. Secretion of calcitonin which lowers serum calcium levels by increasing bone formation (opposes parathyroid hormone)
C. The Action of Thyroid Hormones
1. More T4 is produced than T3 but then changed to T3 which is the more active form
2. Help regulate lipid metabolism
3. Increase the absorption of carbohydrates from the intestine
4. Increase the rate of protein metabolism
5. Increase oxygen consumption of almost all metabolically active tissues in the body. The brain, testes, uterus, lymph nodes, spleen and anterior pituitary are exceptions to this
6. Because of the increase in metabolism and oxygen consumption, there is an increase in body temperature
7. Increase the number and affinity of beta adrenergic receptors in the heart thus increasing its sensitivity to the inotropic and chronotropic effects of catecholamines.
8. Normal growth and development.

Front 7

7. Identify the hormones secreted by the alpha, beta, and delta cells of the pancreas and discuss the interrelated roles of each in metabolism p668

Back 7

Islet of langerhans consist of alpha cells, beta cells, and delta cells. Delta cells secrete somatostatin, which inhibits glucagon and insulin secretion. Beta cells secrete preprionsulin, which is ultimately converted to insulin. Alpha cells produce glucagon, which is secreted inversely to blood glucose concentrations.

Front 8

8. Compare and contrast the adrenocortical and medullary hormones with reference to structure, function, and regulation of secretion by the body systems p672

Back 8

A. The Adrenal Cortex
1. The hormones are all lipids and are synthesized from the cholesterol from LDLs. Most are bound to proteins in circulation
2. The cells are stimulated to produce their hormones by ACTH
3. The hormones
a. Glucocorticoids [the sugar raising (gluco) hormones from the adrenal cortex (corti)]. Cortisol is the main and most potent glucocorticoid.
1. Stimulate glucose formation in the liver by glycogenesis and gluconeogenesis
2. Inhibit the inflammatory response
3. Break down proteins
4. Increase the number of RBC leading to polycythemia
5. Increase the appetite
6. Promote fat deposits, especially in the face and neck
7. Decrease serum calcium levels
8. Suppress ACTH and GH secretion
9. Sensitize arterioles to the vascular effects of norepinephrine
10. Exert an anti-insulin action in peripheral tissues
11. Secretion is regulated by 1) ACTH secretion of the anterior pituitary in response to low levels of circulating cortisol, 2) Diurnal rhythms with the most cortisol being secreted 3 to 5 hours after sleep, and 3) stress.
12. High glucocorticoid levels suppress secretion of ACTH
b. Aldosterone (mineralocorticoids)
1. Think of sodium as a mineral. Its main function is to conserve sodium
2. Increases the activity of the sodium pump
3. Sodium is saved, potassium and hydrogen are lost by the action of aldesterone on the renal tubules and collecting ducts
4. Synthesis and secretion primarily regulated by angiotensen II. Is also affected by sodium and potassium levels
c. Adrenal estrogens and androgens
1. Direct secretion of estrogen by the adrenal cortex is very minimal and has no physiologic effect.
2. Adrenal androgens exert about 20% of the androgenic effect with the rest coming from the testes
3. Secretion of the above is regulated by ACTH, not by Gn
4. Adrenal androgen is converted to estrogen in the circulation.
B. The Adrenal Medulla
1. Secretion of the catecholamines of epinephrine, norepinephrine, and dopamine
2. Secretion affected by the sympathetic nervous system, ACTH, hypoglycemia, emotional or physiologic stress, glucagon, histamine, nicotine, and angiotensin II.
3. Effects in general are hyperglycemia and increased sympathetic tone.
4. Effects of epinephrine
a. Increased force of cardiac contraction
b. Increased heart rate
c. Vasodilation in skeletal muscle and the liver, vasoconstriction in the rest of the body
d. Increased systolic blood pressure with a widening pulse pressure

Front 9

9. Describe the adaptive effects of hormones secreted during the stress response p677

Back 9

Catecholamines bind with various target cells and are taken up by neurons or excreted in the urine. They cause a range of metabolic effects that generally are characterized as the fight or flight response. Endocrine system acts together with the nervous and immune systems to resond to stressors providing an integrated and protective response.

Front 10

10. Describe the effects of normal aging on the endocrine system p677

Back 10

Read pg 679

Front 11

1. Identify the mechanisms of hormonal dysfunction p683

Back 11

A. Alteration in the Feed Back System
B. Not Enough material for the precursors of the hormone
C. The Gland Itself is Malfunctioning (producing more or not enough of the hormone)
D. Degradation of the Hormone Once Released into Circulation
E. Hormones Being Produced by an Ectopic Source, Such as a Tumor
F. Failure of the Target Cell to Respond to the Hormone
1. Decrease in the number of receptors
2. Insensitivity of the receptor to the hormone
3. Antibodies against the receptor
4. Unusual expression of receptor function
G. Not Enough Second Messengers
H. Failure to Generate the Second Messenger Response
I. Alteration of Intracellular Proteins or Enzymes
J. Things to Remember
1. If the disease is called "primary", it means the disease is of the gland being talked about.
2. If the disease is called "secondary" the problem is outside the gland but is affecting it. For example, a disease of the thyroid can be primary (a goiter on the thyroid gland) or secondary (a pituitary tumor that is affecting the release of TSH, or a lesion on the hypothalamus affecting the secretion of thyroid releasing hormone).

Front 12

2. Compare and contrast SIADH and diabetes insipidus including causation, pathophysiology, manifestations, treatment, and prognosis p685

Back 12

A. Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
1. There is too much antidiuretic hormone so the person will not be putting out urine
2. Caused by things like surgery, lung tumors and infections, hypoxia, hypoglycemic meds, nicotine, morphine, general anesthesia
3. If you can't put out urine, you have water overload
4. If you have too much water, than you have hypoosmolality
5. There is dilutional hyponatremia. That means that, if you had the normal amount of vascular fluid, the sodium level would be normal. But now you have increased fluid that is diluting the sodium. Lab reports will show a low sodium level.
6. Because there is very little water going out through the kidneys, the urine will be hyperosmolar. That is, having plenty of solutes (sodium loss equals sodium intake), but no fluid.
7. The symptoms are related to hyponatremia (thirst, dyspnea, fatigue, nausea and vomiting, and neurological signs and symptoms including muscle twitching to convulsions).
8. What your text didn't cover is that this person is in fluid overload increasing work load on the heart with increased preload. These people can go into congestive heart failure quite easily.
9. Treatment
a. Correct the underlying cause
b. Administer hypertonic IV saline solution
c. Severe fluid restriction
d. Careful monitoring
B. Diabetes Insipidus - this is the opposite of SIADH. Now there isn't enough ADH so there is severe loss of fluid through the urine. The control mechanism is gone. Even if you don't drink, you lose large amounts of fluid.
1. Forms
a. Neurogenic - a lesion of the hypothalamus, the nerves running from the hypothalamus to the posterior pituitary, or the posterior pituitary itself
b. Nephrogenic - renal failure where the tubules cannot respond to ADH
c. Psychogenic - intake of large amounts of water which decreases ADH secretion
d. Drugs can cause this disease as well. These include lithium and general anesthetic.
2. Pathophysiology
a. Partial or total inability to concentrate urine with loss of up to 12 liters a day
b. Decreased urine osmolality (low specific gravity) with increased serum osmolality.
3. Signs and Symptoms
a. Polyuria
b. Severe dehydration
c. Spend a lot of time in the bathroom
d. Excessive thirst, for cool liquids
4. Evaluation and treatment
a. Diagnosed by with holding fluids. Urine output will remain high. Have to watch these individuals very carefully during this time. They can go into circulatory collapse from dehydration
b. Treated with ADH replacement. This can be IV or through nasal inhalation. DDAVP is a synthetic vasopressin. Diabenes (oral antidiabetic medication) is used frequently to treat this condition when there is only partial loss of ADH and it works. Potentiates the effect of the ADH the person has.

Front 13

3. Differentiate between primary, secondary, and tertiary causes of endocrine disorders p688

Back 13

B. Clinical Manifestations of the Acute Complications of Diabetes
1. Hypoglycemia
a. Neurogenic
1. Tachycardia
2. Palpitations
3. Sweating
4. Tremors
5. Pallor
6. Anxiety
b. Neuroglycopenic
1. Confusion
2. Headache
3. Irritibility
4. Hunger
5. Seizures
c. Things to remember
1. These symptoms can come on suddenly and are life threatening
2. With long standing diabetes, and associated with the chronic complications of neuropathy, the neurogenic signs and symptoms may be blocked.
3. Beta blockers also block the neurogenic signs. This is dangerous as the diabetic may be too confused to treat the hypoglycemia
C. Hyperglycemia
1. Diabetic Ketoacidosis - associated with type I diabetes
a. Blood sugars can be up to 600
b. Lack of insulin with an increase in couterregulatory hormones
c. Usually precipitated by an illness such as an infection or trauma or stress
d. Comes on more slowly
e. Experience the cardinal symptoms of hyperglycemia as well as
1. Dry, flushed skin
2. Dry mucous membranes
3. Low blood pressure
4. Ketosis (acidosis) from using fats for energy
5. Low intracellular potassium levels even though the serum level may be normal. Related to the shift of potassium from inside to outside the cell related to acidosis
6. Kussmaul respirations
f. Treatment
1. Low dose insulin either by continuous infusion or SQ administration. Want to drop the blood sugar slowly.
2. Fluids to treat the dehydration
3. Replacement of electrolytes. This has to be done very carefully. Potassium levels have to be checked frequently. As the acidosis decreases, and insulin is available to the cells, the potassium will begin to reenter the cell leaving a large potassium deficit.
2. HHNK - associated with type II diabetes
These people have severe hyperglycemia, 800 and above
a. Slow onset caused by the same reasons as above
b. Severe dehydration from the osmotic force of the high blood glucose levels
c. The diabetic may be stuporous
d. Extremely hyptonic urine
e. The prognosis for this complication can be poor if fluid replacement is not instituted quickly and if fluids are not given at a sufficient rate (up to 2000ml in the first hour)
f. Low potassium levels that may take a while to correct
D. Diagnosis of Diabetes
1. Patient history
a. Cardinal symptoms of polyuria related to osmotic diuresis from hyperglycemia, polydypsia related to the dehydration from increased diuresis, and polyphagia related to cellular starvation from lack of available glucose
b. Weight loss
c. Sticky urine
d. Fatigue
e. An infection or sore that does not heal
2. Glucose tolerance test (not usually needed with type I diabetes)
3. Fasting blood sugars
a. More than one fasting with the plasma level over 126
b. Plasma level over 200 without regard to the last meal and with the cardinal symptoms of diabetes
4. Glycosolated Hemoglobin
a. Not used to diagnose diabetes but to determine control
b. Based on the premise that the amount of glucose on the hemoglobin A1c molecule is directly related to the plasma glucose level.
c. Done no oftener than every 120 days as that is the life of the RBC
E. Special Problems Associated With Type I Diabetes
1. Somogyi Effect
a. Hypoglycemia during the night which the body tries to correct by release of insulin couterregulatory hormones (epinephrine, growth hormone, cortisol, and glucagon)
b. The person then demonstrates hyperglycemia in the early A.M.
c. Treatment is not more insulin but rather decreasing the dose or changing the time of administration
2. Dawn Phenomenon
a. Hyperglycemia in the morning, with no hypoglycemia during the night
b. Related to the increase in GH that happens during the night
c. Altering time and dose of insulin is the treatment
F. Chronic Complications
1. Diabetic neuropathies
2. Microvascular disease
a. Retinopathy
b. Nephropathy
3. Macrovascular Disease
a. Atherosclerosis
b. Coronary artery disease
c. Stroke
d. Peripheral vascular disease
4. Infection

Front 14

4. Discuss the causes of hyperpituitarism and hypopituitarism with consideration of the populations at risk p687

Back 14

A. Panhypopituitarism Means There is a Deficiency in All the Tropic Hormones on the Pituitary, so All Target Organs are Affected.
B. Partial Hypopituitarism
1. Usually caused by an infarct to the pituitary gland postpartum. Also caused by changes in vasculature related to other disease processes such as diabetes mellitus, shock, sickle cell disease, or infections of the CNS. Can also be caused by lesions or surgery.
2. The signs and symptoms are related to which tropic hormone(s) is/are deficient
a. ACTH - decreased cortisol levels (will look at this with the study of Addison's Disease)
b. TSH - Hypothyroidism
c. FSH and LH - gonadal failure and loss of secondary sex characteristics
d. GH - dwarfism
e. Prolactin - inability to produce breast milk
3. Evaluated by history and testing for levels of the hormones by radioimmunoassay. Also do x-rays of the sella turcica.
4. Treated by treating the cause if that is possible. The involved hormones will need to be replaced.
C. Hyperpituitarism
1. Usual cause is a primary adenoma, which is a benign slow growing tumor.
2. The adenoma secretes the hormone of the cell type from which it arises.
3. It is not subject to the negative feedback system
4. As the adenoma grows, it will exert pressure on other parts of the pituitary. Those cells, like GH cells and LH and FSH cells that are sensitive to pressure, will start secreting less of their hormone.
5. Signs and symptoms are related to the cells effected either by the tumor or by the pressure exerted by the tumor
6. Clinical evaluation starts with a history followed by radioimmunoassay, x-rays, CT scan
7. Treatment consists of surgical removal of the adenoma and radiation. The surgery is usually done via the transsphenoidal approach. This way they don't have to do a craniotomy. Think of the risk of infection going through the mouth and the sphenoidal sinus, which is so close to the nose. But, it works.
8. Excess growth hormone
a. If present in a child whose epiphyseal plate has not closed, the child becomes a giant (giantism).
b. If present in an adult, the term is acromegaly
c. Usually caused by a GH secreting adenoma
d. Epiphyseal plate has closed in an adult, so there is overgrowth of connective tissue as well as bony proliferation. There can also be enlarged organs
e. Because GH is a counterregulatory hormone against insulin, there is hyperglycemia.
f. What does this person look like?
1. Large protruding tongue
2. Thick skin
3. Interstitial edema
4. Coarse hair
5. Enlarged facial features as well as enlarged hands and feet
6. Jaw and forehead protrude
7. There can be hypertension and left sided heart failure
8. Barrel chest
g. Evaluation and treatment
1. Radioimmunoassay of GH
2. X-rays, CT scan
3. Radiation - surgical removal of the adenoma (treatment of choice)

Front 15

5. Discuss Grave's disease and thyroid storm including cellular changes, manifestations, treatment, and complications p693

Back 15

A. Graves Disease (multisystems syndrome; exophthalmic goiter)
1. Cause
a. Autoimmune where T cells activated by antigens in the thyroid gland stimulate B cells to produce circulating antibodies (IgG) against the thyroid cell's antigen. They think there is a defect in Ts cells that permit the Th cells to stimulate the B cells to produce the thyroid antibodies. These antibodies effect the receptors for TSH and are call thyroid stimulating immunoglobulins. The result is thyroid hyperplasia and increased iodine uptake with over secretion of thyroid hormones. The high levels of thyroid hormones than depress the production of TSH.
b. Familial
2. One or more of the following are present
a. Hyperthyroidism
b. Goiter
c. Ophthalmopathy
1. Functional abnormalities with lag of the eye when turned upward, or lag of the lid when the eye is turned downward
2. Swelling of the extraocular muscles which then pushes the eyeballs forward (exophthalmos)
d. Dermopathy - The skin on the front of the lower legs become hard and red, and there is swelling.
B. Thyrotoxic Crisis - Thyroid Storm
1. Seen in individuals who have thyrotoxicosis, but there has been some added physical or emotional stress.
2. The signs and symptoms are the same as thyrotoxicosis, but much more severe and life threatening. This is high output heart failure time. They have a big increase for the need of oxygen related to the increased metabolic rate resulting in increased use of oxygen.
3. Treatment
a. Medications that impair synthesis of thyroid hormone or that block the action of the thyroid hormone
b. Adrenergic blocking agents to decrease cardiac work load
c. Oxygen
d. Iodine. It reduces the vascularity of the gland and works temporarily to prevent the release of TH into the circulatory system. It does this by increasing the amount of TH that is stored in the gland. Now, sooner or later, the stored TH will be liberated. That is why this is temporary and is done prior to partial (done for hyperthyroidism) or total thyroidectomy (done for cancer of the thyroid)
e. Surgery - It is important for the individual to be euthyroid prior to surgery. Approximately 5/6 of the gland is removed. Iodine to decrease vasculization and thus bleeding, and antithyroid medications are given. Usually, with even just 1/6 of the gland left, there will not be need for thyroid replacement post operatively.
f. Radioactive Iodine - this therapy is reserved for the older folks. They drink a radioactive iodine laced drink, the thyroid takes it up as iodine, and the radioactive iodine destroys thyroid tissue.

Front 16

6. Compare and contrast the causes, treatment options, and outcomes for disorders producing hypothyroidism p694

Back 16

A. Hypothyroidism
1. Is by far the most common disorder of the thyroid
2. Primary disease caused by
a. Circulating thyroid antibodies against the thyroid gland (Hashimoto disease)
b. Thyroiditis (usually bacterial)
c. Decreased iodine intake
d. Antithyroid medications
e. Congenital defects
f. Loss of thyroid tissue from surgery or radioactive iodine
3. Secondary disease caused by
a. Decreased amount of TSH from the pituitary or decreased amounts of TRH from the hypothalamus. Pituitary infarcts or tumors are the most frequent causes.
b. Peripheral resistance to circulating TH
4. Types of hypothyroidism
a. Primary - Decreased levels of TH related to loss of functioning thyroid tissue. This causes an increase of TSH that leads to goiter.
b. Congenital - There is lack of thyroid tissue or a defect in thyroid hormone synthesis.
1. Mentally retarded if no thyroxine during fetal life
2. May take up to 4 months for the symptoms to occur
3. Symptoms are opposite of hyperthyroidism as now the metabolism is slowed
4. Cretinism (dwarf with short limbs)
5. There can be a high rate of normal growth and development as well as a high possibility of normal intellect if treatment is started early
c. Thyroid cancer
5. Clinical Manifestations
1. Usually insidious
2. Dependent on the level of decrease of circulating thyroid hormones
3. Affects all body systems
4. There is a low metabolic rate with intolerance to cold. The person is tired all of the time, they gain weight even though they have a decreased appetite, and there is fluid retention. These people think and talk slowly, experience decreased cardiac output related to a reduction in stroke volume and heart rate, and there is increased peripheral vascular resistance to maintain the blood pressure. The heart is enlarged, the person complains of dyspnea, and there is decreased blood flow to the kidneys, anemia, and dry and flaky skin (see table 20- 2 pages 669 and 670).
5. Myxedema coma
a. Diminished level of consciousness with severe hypothyroidism
b. Symptoms include decreased body temperature, hypoventilation, hypotension, hypoglycemia, and lactic acidosis
c. Is a medical emergency
d. Usually occurs in our elderly folks who have severe vascular disease and untreated hypothyroidism. Also occurs in those with hypothyroidism and overuse of sedatives or narcotics or those who have a bad infection
6. Diagnosis
. History
a. Decreased levels of thyroid hormones
b. Increased levels of TSH
c. Decreased basal metabolic rate
7. Treatment
. Thyroid - usually in a synthetic form. There are a lot of people on thyroid. Good thing it is relatively inexpensive.
a. The goal is a euthyroid state.

Front 17

7. Identify the causes, manifestations, and treatment of disorders of the parathyroid glands p698

Back 17

A. Hyperparathyroidism
1. Primary - over secretion of PTH by one or more of the parathyroid glands usually caused by a tumor
2. Secondary - a decrease in the level of circulating ionized calcium which then stimulates PTH production and is usually due to renal failure
3. Remember - an increase in PTH means an increase in circulating calcium!
4. Clinical manifestations
a. Excessive osteoclastic and osteocytic activity resulting in bone with low density, bone pain and pathological fractures. The calcium that is in the circulation has come from the bones.
b. Hypophosphatemia - remember that calcium and phosphate are inversely related so phosphate is excreted in the urine
c. Calcium is also excreted in the urine, so now we have calcium based kidney stones which can cause renal damage
d. Impairment of the concentrating ability of the renal tubule as hypercalcemia decreases the renal response to ADH
e. Causes insulin resistance
f. Decreased neuromuscular irritability
5. Diagnosis
a. Increased serum calcium levels
b. History of calcium based kidney stones
c. Hypophosphatemia
d. PTH levels
e. Bone x-rays and density studies
6. Treatment
a. Lower serum calcium levels
1. Hydration
2. Loop diuretics (Lasix)
3. Calcitonin
4. Phosphates
5. Gallium nitrate
6. Low calcium diet
7. Surgical removal of the parathyroid gland that is over secreting
B. Hypoparathyroidism
1. Most commonly caused by damage to the parathyroids during thyroid surgery
2. Can also be caused by low levels of magnesium
3. There is low PTH causing low circulating calcium levels and hyperphosphatemia
4. Now, the calcium is being moved back into the bone related to decreased PTH levels
5. Clinical Manifestations
a. Lowers the threshold for nerve and muscle excitation so a nerve impulse can be initiated by a slight stimulus anywhere along the fiber causing muscle twitching, numbness and tingling especially around the mouth and in the fingers, laryngeal spasms which may lead to airway closure, tetany, convulsions, and death.
b. The elevated phosphate levels inhibit the renal enzyme that is necessary for the conversion of Vitamin D to its active form which decreases the serum calcium level even more.
6. Diagnosis
a. Low serum calcium and high phosphorus levels
7. Treatment
a. Administration of calcium

Front 18

8. Describe the similarities and differences in the etiology and pathophysiology of Type I and Type II diabetes mellitus p710

Back 18

DIABETES TYPE I DIABETES TYPE II
Cause Autoimmune with cell-mediated destruction of beta cells.
Genetic susceptibility with an HLA-DR3 and HLA-DR4 link Unknown but genetics suspected because of the familial tendency of this disease, especially if the father was the diabetic
Pathophysiology Antibodies against the beta cells
Antibodies against insulin
Excessive glucagon secretion
Severely decreased to no insulin production
Suspected environmental trigger (virus, stress) Defects in insulin secretion related to decrease in weight and number of beta cells
Insulin resistance
Related to obesity
May have normal insulin levels
Insulin receptor abnormalities
Post-receptor defects
Increase in glucagon levels
Physical Characteristics of the person Usually thin
Young - rare before the age of 2, rate increases at puberty, up to about age of 30 Obese
Incidence increases with age
Inactive
Onset of Disease Autoantibodies present for some time, but the onset of the disease is abrupt. Insidious onset
Usually diagnosed when the person goes in because a sore doesn't heal, the presence of a fungal infection, or pre-surgical screening
Treatment Tight control
Insulin required via SQ injection
Diet
Exercise Diet (the mainstay) with weight loss in the obese
Exercise
Oral antidiabetic medications
Insulin may be required
Acute Complications Hypoglycemia related to too much insulin, too little food, over exercise.
Hyperglycemia with ketosis and metabolic acidosis Hypoglycemia can occur with oral antidiabetic medications as well as those causes under Type I.
Hyperglycemia - ketones not usually present
Hyperosmolar hyperglycemic nonketotic coma (HHNK)

Front 19

9. Describe the acute complications of diabetes mellitus with a focus on differential diagnosis and treatment p710

Back 19

B. Clinical Manifestations of the Acute Complications of Diabetes
1. Hypoglycemia
a. Neurogenic
1. Tachycardia
2. Palpitations
3. Sweating
4. Tremors
5. Pallor
6. Anxiety
b. Neuroglycopenic
1. Confusion
2. Headache
3. Irritibility
4. Hunger
5. Seizures
c. Things to remember
1. These symptoms can come on suddenly and are life threatening
2. With long standing diabetes, and associated with the chronic complications of neuropathy, the neurogenic signs and symptoms may be blocked.
3. Beta blockers also block the neurogenic signs. This is dangerous as the diabetic may be too confused to treat the hypoglycemia
C. Hyperglycemia
1. Diabetic Ketoacidosis - associated with type I diabetes
a. Blood sugars can be up to 600
b. Lack of insulin with an increase in couterregulatory hormones
c. Usually precipitated by an illness such as an infection or trauma or stress
d. Comes on more slowly
e. Experience the cardinal symptoms of hyperglycemia as well as
1. Dry, flushed skin
2. Dry mucous membranes
3. Low blood pressure
4. Ketosis (acidosis) from using fats for energy
5. Low intracellular potassium levels even though the serum level may be normal. Related to the shift of potassium from inside to outside the cell related to acidosis
6. Kussmaul respirations
f. Treatment
1. Low dose insulin either by continuous infusion or SQ administration. Want to drop the blood sugar slowly.
2. Fluids to treat the dehydration
3. Replacement of electrolytes. This has to be done very carefully. Potassium levels have to be checked frequently. As the acidosis decreases, and insulin is available to the cells, the potassium will begin to reenter the cell leaving a large potassium deficit.
2. HHNK - associated with type II diabetes
These people have severe hyperglycemia, 800 and above
a. Slow onset caused by the same reasons as above
b. Severe dehydration from the osmotic force of the high blood glucose levels
c. The diabetic may be stuporous
d. Extremely hyptonic urine
e. The prognosis for this complication can be poor if fluid replacement is not instituted quickly and if fluids are not given at a sufficient rate (up to 2000ml in the first hour)
f. Low potassium levels that may take a while to correct
D. Diagnosis of Diabetes
1. Patient history
a. Cardinal symptoms of polyuria related to osmotic diuresis from hyperglycemia, polydypsia related to the dehydration from increased diuresis, and polyphagia related to cellular starvation from lack of available glucose
b. Weight loss
c. Sticky urine
d. Fatigue
e. An infection or sore that does not heal
2. Glucose tolerance test (not usually needed with type I diabetes)
3. Fasting blood sugars
a. More than one fasting with the plasma level over 126
b. Plasma level over 200 without regard to the last meal and with the cardinal symptoms of diabetes
4. Glycosolated Hemoglobin
a. Not used to diagnose diabetes but to determine control
b. Based on the premise that the amount of glucose on the hemoglobin A1c molecule is directly related to the plasma glucose level.
c. Done no oftener than every 120 days as that is the life of the RBC
E. Special Problems Associated With Type I Diabetes
1. Somogyi Effect
a. Hypoglycemia during the night which the body tries to correct by release of insulin couterregulatory hormones (epinephrine, growth hormone, cortisol, and glucagon)
b. The person then demonstrates hyperglycemia in the early A.M.
c. Treatment is not more insulin but rather decreasing the dose or changing the time of administration
2. Dawn Phenomenon
a. Hyperglycemia in the morning, with no hypoglycemia during the night
b. Related to the increase in GH that happens during the night
c. Altering time and dose of insulin is the treatment
F. Chronic Complications
1. Diabetic neuropathies
2. Microvascular disease
a. Retinopathy
b. Nephropathy
3. Macrovascular Disease
a. Atherosclerosis
b. Coronary artery disease
c. Stroke
d. Peripheral vascular disease
4. Infection

Front 20

10. Compare the causation, cellular changes, clinical manifestations, treatment and complications of the disorders of the adrenal glands p720

Back 20

See book.