Pathophysiology 2 exam 2 UCF
Type 2 DM
-Adult (40s &50s) -genetic, but diff from type 1 -NOT autoimmune -insulin may be low, BUT peripheral resistance to insulin is the main factor -OBESE patients -not prone to ketoacidosis or diabetic complications -risk factors: high BMI, fam. history of DM2, ethnic minority, FEMALE GENDER -treatment: Diet, exercise, oral glycemic agents, possibly insulin *stomach changes food into glucose --> glucose enters the bloodstream --> the pancreas makes insulin --> insulin enters the bloodstream --> glucose can't get into the cells of the body. Glucose builds up in the blood vessels.* *insulin is less able to facilitate entry of glucose into liver, skeletal muscle, and adipose tissue, Pancreas eventually burns out.*
In the 'fed state', glucose....
-Glucose provides primary energy source -Amylin acts on area postrema (AP) -INSULIN dominated
Cortisol is the most significant glucocorticoid
-Released in response to ACTH, patterns of eating and activity, and stress -Prime metabolic effect is gluconeogenesis—formation of glucose from fats and proteins -Promotes rises in blood glucose, fatty acids, and amino acids
Glucose - urinary glucose
-Renal threshold for glucose is 180 mg/dl, and in diabetics it is increased to 300 mg/dl. -urinary glucose is a POOR marker for DM.
Postprandial plasma glucose test
-a high in carb meal is used (75g glucose drink is preferred) as carb load, Pepsi. -plasma glucose is measured 2 hours after carb ingestion -two postprandial tests with glucose levels >or equal to 22 mg/dl are suggestive of diabetes.
Oral glucose tolerance test (OGTT)
-carb intake is controlled 3 days before test -glucose load is 40 g glucose/m^2 body area -blood glucose is measured 2 hours after glucose load -glucose level > or equal to 200 mg/dl is suggestive of diabetes.
Type 1 DM
-childhood onset -genetic -insulin deficit -autoimmune -antibodies to beta cells, insulitis -beta cell depletion -NON-OBESE patients -prone to ketoacidosis & diabetic complications -Treatment: insulin replacement balanced with exercise and diet (short term), A1C (long term) *stomach converts food to glucose --> glucose enters bloodstream --> pancreas produces little or no insulin --> glucose unable to enter body effectively --> glucose levels increase*
Insulin - Liver
-decreased gluconeogenesis -increased glycogen synthesis increased lipogenesis
Manifestations of Hyperglycemia
-directly after eating, the blood sugar will rise -the beta cells from the pancreas are then triggered to release insulin into the blood -insulin acts like a key in the cell membrane to open the door for glucose to enter the cell -the cell will use the glucose for ATP (energy) and store the surplus -when glucose leaves bloodstream and enters the cells, the blood glucose levels return to a normal level
Homestatic inbalances of Insulin - DM
-due to hypo secretion or hyperactivity of insulin -three cardinal signs: polyuria (huge urine output), polydipsia (excessive thirst), and polyphagia (excessive hunger and food consumption)
Hyperglycemia
-excess of sugar in the blood -more than one fasting plasma glucose level (>126) -elevated plasma glucose in response to an oral glucose tolerance test (>200) -Random plasma glucose >200
Diagnostic tests for DM - Other tests
-glucose -glycation hemoglobin -albumin (protein) -insulin -keto acids -hydrogen ion -electrolytes -osmolality -Body fluid volume -anion gap -BUN -lipids
Type 1 DM recap*
-high blood glucose levels -NO insulin production -beta cell destruction, most likely the result of autoimmunity -controlled by insulin replacement therapy *fasting plasma insulin is low*
Type 2 DM recap*
-high blood glucose levels -target tissues fail to respond appropriately to insulin; the inability of the beta cells to compensate -inherited predisposition coupled with diet and lifestyle *fasting plasma insulin is normal, it is high if plasma glucose >250 mg/dl*
Regulation of glucose metabolism
-hormonal regulation* -Glucose-dependent insulinotropic polypeptide (GIP) -Glucagon-like peptide (GLP-1): from cells in the gut, stimulate the production of insulin and inhibit glucagon.
More risk factors for DM
-hypertension (>140/90) -low high-density lipoprotein (HDL) cholesterol concentrations (<35 mg/dl) -elevated triglyceride concentrations (>250 mg/dl)
Insulin - Muscle
-increased glucose uptake -increased glycogen synthesis -increased protein synthesis
Insulin - Fat
-increased glucose uptake -increased lipogenesis -decreased lipolysis
Type 1 - glucose tolerance test
-individual is given 50-100g of glucose dissolved in water; blood glucose is measured at 1, 2, and 3 hours. Expected values: 120-160 mg/dl at 1 hour & 70-120 mg/dl at 2 hours
Pathogenesis of DM - Insulin receptor defects
-insulin resistant:can be due to malfunction in insulin receptor, but the cause is NOT KNOWN in type 2. -Antibodies to insulin receptor: in type 2
Keto Acids
-measured in both blood and urine. -plasma kept acids may be normal even though urinary kept acids are high, this is due to increase urinary excretion of kept acids from renal compensation to low pH. -controlled diabetics should have normal plasma and urinary kept acids levels.
MODY (maturity onset diabetes of the young)
-multiple types -2-5% of diabetics -primary beta cells defects -multiple genetic mechanisms, especially GLUCOKINASE mutations
Acute complications: Protein glycation
-nonenzymatic binding of free amino groups of proteins to glucose and other sugars -protein glycation commonly occurs in RBCs, glomeruli, nerve cells, and other tissues -extent of protein glycation is proportional to extracellular glucose concentration -Excessive glycation causes alterations in proteins physical and biochemical properties -new research suggest that many diabetes complications are caused by glycation of specific proteins.
Clinical manifestations
-polyuria, nocturia, glycosuria (excess glucose in the urine) = hyperglycemia draws fluids into the intravascular space, glucose acts as a diuretic leading to large volumes of urine being filtered by the kidneys and excreted; the kidneys allow excess glucose to spill out into the urine. -polydipsia, dry mouth = cellular dehydration and the stimulation of thirst by the hypothalamus. -polyphagia, weight loss, fatigue = insulin deficit disallows use of glucose for energy; storage of fats, proteins, and carbs begin to deplete; cells are in state of starvation because of lack of nutrients --> hunger. -blurred vision = lens and retina are exposed to hyperosmolar fluids.
Diagnostic tests for DM - Function tests
-postprandial plasma glucose -oral glucose tolerance test both tests measure clearance rate of glucose load from the blood.
Gestational DM
-pregnancy -insulin resistance during pregnancy as a result of too much hormone production in the body (for the placenta); inability to make the additional insulin that is needed during pregnancy -Treatment: Diet, exercise, sometimes insulin, delivery of baby
Regulation of glucose metabolism - Stress
-production of stress hormones (corticosteroids and catecholamines) increase production of glucose -increase production of FFAs (?) -Lead to hyperglycemia
Glucose - fasting plasma glucose
-repeated levels >126 mg/dl = strongly suggest diabetes. -levels 100-126 mg/dl = impaired fasting glucose. -increase in fasting plasma glucose os directly proportional to severity of DM.
Albumin
-urinary protein (microalbuminuria) is one of the earliest signs of glomerular nephropathy. -Albumin/creatinine >or equal to 20-30 mg/day suggests microalbuminuria. -Without intervention --> macroalbuminuria (>300 mg/dl), leading cause of END STAGE RENAL DISEASE in US.
who has DM?
69K people die of it per year in the USA -cost: $245 billion: total coasts of diagnosed diabetes in the US since 2012
What is the normal glucose level?
70-120 mg/dl
Islet of Langerhans
A group of beta cells
What are the etiologic factors, clinical findings, and management of adrenal medullary hormone excess?
A pheochromocytoma is the most common cause of adrenal medullary hormone excess. Typical symptoms include intermittent or persistent hypertension, headache, tachycardia, tremor, and irritability. It is treated with surgical removal of the tumor
What are the etiologic factors, clinical findings, and management of antidiuretic hormone (ADH) excess and deficiency?
ADH deficiency can result in central diabetes insipidus, which can be idiopathic or related to brain surgery, trauma, or tumor. Manifestations include polydipsia, accompanied by thirst, polyuria, and increased serum sodium and osmolality. Central diabetes insipidus is treated with ADH hormone replacement therapy and fluids. ADH excess can result in syndrome of inappropriate anti-diuretic hormone (SIADH), which is associated with pulmonary tumors, central nervous system disease, and certain drugs. Manifestations include oliguria, and symptoms are associated with hyponatremia, such as neurologic dysfunction, confusion, and coma. Water restriction and diuretics are commonly used to manage hyponatremia
What are the acute and chronic complications of diabetes mellitus?
Acute complications of diabetes mellitus include hyperosmolar coma, ketoacidosis, and infection. Chronic complications include vascular complications, such as cardiovascular disease, stroke, and peripheral vascular disease; retinopathy; nephropathy; and neuropathy
Complications of hyperglycemia
Acute: diabetic ketoacidosis (too little insulin causes ketones to form). Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)... massive osmotic diuresis & hypotension. Chronic: glycosylation of various tissues
What are the etiologic factors, clinical findings, and management of adrenocortical hormone excess and deficiency?
Adrenocortical hormone deficiency may be due to Addison disease, autoimmune destruction, surgical removal, or due to lack of secretion of ACTH from the pituitary gland. Manifestations include weight loss, salt wasting, volume depletion, low blood pressure, hypoglycemia, and hyperkalemia. Treatment includes hormone replacement therapy. Excess cortisol (Cushing disease) is due to pituitary hyperstimulation of the adrenal cortex. ACTH excess may be due to pituitary adenoma or exogenous production by nonpituitary tumors. Clinical manifestations include moon facies, cervical fat pad, central obesity, thin extremities, weight gain, thin skin, striae, hypertension, and hyperglycemia. Surgical removal of the ACTH-producing tumor or removal of the adrenal gland is the usual treatment. Primary hyperaldosteronism (Conn syndrome) is due to adrenal tumor, which is treated with tumor removal. Typical symptoms include hypervolemia, hypertension, and hypokalemia
HYP____A.P._____Adrenal Gland_____
CRH, ACTH, Cortisol
Chronic complications - Microvascular disease
Capillary basement membrane thickening - ischemia. -retinopathy -diabetic nephropathy
Lipolysis
Catabolic degradation of triacylglycerol.
Pathogenesis of DM - Type 2 DM
Caused by a defect in glucose transport after insulin binds to its receptor.
Pathogenesis of DM - Type 1 DM
Caused by destruction of Islet cells as a result of autoimmune reaction to beta cells.
What clinical findings are associated with hyperglycemia, and how do they differ from those of hypoglycemia?
Clinical manifestations of hyperglycemia include polydipsia, polyuria, and polyphagia, which may be accompanied by nausea, fatigue, and blurred vision. In contrast, clinical findings in hypoglycemia include pallor, tremor, diaphoresis, palpitations, anxiety, hunger, visual disturbance, weakness, paresthesias, confusion and agitation
Hormonal regulation of glucose metabolism - Insulin
Decreases blood glucose
In higher doses Glucocorticoids (cortisol)
Depress cartilage and bone formation Inhibit inflammation--Anti-inflammatory effects (treatment for chronic inflammatory diseases) Depression of immune function (Prescribed for organ transplants)
Acute complications: Causes of fasting Hypoglycemia
Depressed blood insulin/decreased glucose production, liver disease, alcoholism, renal insufficiency, Galactosemia and glycogen storage disease, malignancy (increases consumption of glucose or production of insulin-like growth factor), infection, late pregnancy, malnutrition, overtreatment with insulin (insulinoma, factitious treatment with insulin, treatment with sulfonylurea drugs, anti insulin antibodies).
Secondary DM
Diabetes caused by various secondary conditions such as pancreatic disease, acromegaly, cushings syndrome, pheochromocytoma, glucagonoma, somatostatinoma, primary aldosteronism, sever liver disease, and certain drugs, chemicals, and hormones.
How is diabetes mellitus diagnosed, monitored and managed?
Diabetes is diagnosed if any of the following conditions occurs on more than one occasion: a random sampling of blood glucose above 200 mg/dl with classic signs and symptoms, a fasting blood glucose level of greater than 126 mg/dl, or a blood glucose concentration greater than 200 mg/dl 2 hours after a 75-g oral glucose load. Diabetes mellitus is monitored through measurement of preprandial and postprandial blood glucose levels, measurement of HbA1C, and routine evaluations of secondary complications. The disease is managed through dietary modifications, exercise, pharmacological agents including insulin therapy, stress management, and family/patient education
What etiologic factors would lead to clinical manifestations of hormone excess or deficiency?
Etiologic factors that can lead to clinical manifestations of hormone excess or deficiency include genetic defects, autoimmune disorders, production by abnormal tissue sites, endocrine disease, treatment-induced mechanisms, or iatrogenic disorders
Type 1 - Glycosylated hemoglobin (A1C) test
Expected values: 2-6%
Pathogenesis of DM - HLAs
Expression of certain HLAs is associated with increased susceptibility to type 1 diabetes
Glycoproteins
FSH, LH, TSH
How are thyroid hormones synthesized?
Follicular cells of the thyroid gland perform all the functions required to make and secrete thyroid hormones. They trap dietary iodine and transport it into the colloid, synthesize thyroglobulin protein, and transport it into the colloid along with the enzyme thyroid peroxidase. Thyroid peroxidase oxidizes iodide and couples it to tyrosine amino acids in thyroglobulin. Two iodotyrosines are then attached together to form T4 or T3.
Lipogenesis
Formation of fats.
Gluconeogenesis
Formation of glucose from excess amino acids, fat, and other noncarbohydrate sources.
Glycogenesis
Formation of glycogen.
HYP____A.P.____liver_____
GHRH, GH, GF-
Alpa cells
Glucagon
In the 'fasting state', glucose....
Glucose is produced by glycogenolysis and gluconeogenesis -GLUCAGON dominates
Normal Glucose Homeostasis is regulated by: (3)
Glucose production in the liver, Glucose uptake and utilization by peripheral tissues (skeletal muscle), and actions of hormones.
HYP____A.P._____Gonads_____
GnRH, FSH/LH, estrogen & progestrone or testostrone
What are the etiologic factors, clinical findings, and management of growth hormone excess and deficiency?
Growth hormone (GH) deficiency may be idiopathic or related to tumors, radiation, or trauma. It can result in decreased linear growth. Management includes hormonal replacement, particularly in children. GH excess (acromegaly) is usually due to a pituitary adenoma and can result in increased linear growth and giantism, including a protruding jaw, increased bone density, increased growth of soft tissues and large hands and feet. Treatment entails surgical removal or pharmacologic palliation of the pituitary tumor
Glycolysis
Hydrolysis of glucose to pyruvate.
What are the etiologic factors, clinical findings, and management of parathyroid excess and deficiency?
Hyperparathyroidism may be idiopathic or may be due to a parathyroid adenoma. Its manifestations result from high serum calcium levels and bone demineralization, leading to decreased neuromuscular excitability. Treatment entails removing the abnormal glands or tumor. Hypoparathyroidism may be idiopathic, autoimmune, or secondary to surgical removal of the parathyroid gland. The manifestations result from low serum calcium levels, which increase neuromuscular excitability resulting in paresthesias, cramps, spasms, tetany, and seizures. Treatment entails calcium and vitamin D supplementation rather than parathyroid hormone replacement
What are the etiologic factors, clinical findings, and management of thyroid hormone excess and deficiency?
Hypothyroidism may be due to congenital agenesis, autoimmune destruction, irradiation, trauma, surgical removal of the gland, or iodine deficiency. Manifestations include nonpitting edema, slowed mentation, weight gain, dry skin, constipation, decreased heart rate, decreased pulse pressure, lethargy, and loss of the outer third of the eyebrow. Treatment centers on hormone replacement therapy. Hyperthyroidism may be due to Graves disease, autoimmune, tumor-related or inflammatory disorders. Manifestations include hyperactivity, irritability, insomnia, weight loss, increased appetite, heat intolerance, diarrhea, and palpitations. Treatment includes drugs that inhibit thyroid production, radioactive iodine to destroy part of the thyroid gland, medications to alleviate symptoms (beta-blockers) or surgical removal of all or part of the thyroid gland
How do the pathophysiologic processes differ among the various types of diabetes?
In type 1 diabetes mellitus, the production of glucose by the liver is no longer opposed by insulin. Overproduction of glucagon by pancreatic α cells stimulates glycogenolysis and gluconeogenesis. Insulin deficiency and other hormonal influences lead to lipolysis resulting in fatty acids, which undergo transformation into ketoacids in the liver. Type 2 diabetes mellitus starts with the development of insulin resistance, which is initially compensated for by increased insulin production and hyperinsulinemia. Decompensation occurs as the impaired β cells are unable to produce sufficient insulin to overcome insulin resistance. Insulin levels, however, remain elevated above normal until later in progression of the disease. Relatively decreased insulin levels, continued insulin resistance, and hyperglucagonemia result in the hyperglycemia. Gestational diabetes mellitus closely resembles the pathophysiologic characteristics of type 2 diabetes mellitus. Tissue insulin resistance is present, likely precipitated by the presence of placental hormones, with resulting inability to produce sufficient insulin to meet metabolic demands
Hormonal regulation of glucose metabolism - Cortisol & Adrenal Corticosteroids
Increases blood glucose
Hormonal regulation of glucose metabolism - Epinephrine
Increases blood glucose
Hormonal regulation of glucose metabolism - Glucagon
Increases blood glucose
Hormonal regulation of glucose metabolism - Growth Hormone
Increases blood glucose
Hormonal regulation of glucose metabolism - Thyroxine
Increases blood glucose
Hormonal regulation of glucose metabolism - Somatostatin
Inhibits insulin and glucagon
Proteins
Insulin Glucagon GH Prolactin
Addisonian crisis/ acute adrenal insufficiency
Life-threatening condition caused by inadequate levels of glucocorticoids and mineralocorticoids in circulation
What are the general mechanisms of action of lipid-soluble and water-soluble hormones on target cells?
Lipid-soluble hormones diffuse through the lipid-containing cell membrane to activate intracellular receptors in the cytoplasm or nucleus. Water-soluble hormones are unable to cross the plasma membrane to enter cells and therefore must exert their actions by binding to receptors located on the surface of target cell membranes
Pathogenesis of DM - Glucose transport
Low levels of glucose transporters in type 1 and 2.
How can primary and secondary endocrine disorders be differentiated?
Measurement of serum concentrations of pituitary and target gland hormones allows differentiation between primary and secondary endocrine etiologies
Chronic complications - Diabetic neuropathies
Most common complication in Western countries, nerve cell damage - more sensory than motor
F cells
Pancreatic Polypeptide cells
Water soluble
Peptides (proteins) & tyrosine-derived catecholamines (epi, norepi, and dopamine) -on the surface
Impaired fasting glucose
Person exhibiting a fasting plasma glucose level between 1000 mg/L and 1260 mg/L
Impaired glucose tolerance
Person who exhibition their oral glucose tolerance test a 2-hour value between 1400 mg/L and 2000 mg/L
Potential abnormality of glucose tolerance
Persons not presently exhibiting any indications of diabetes but at substantially increased risk to develop diabetes in the future; person who has parent, sibling, or offspring who is type II diabetic; obese individuals; members of certain ethnic or racial groups with a high prevalence of diabetes.
Statistical risk classes: previous abnormality of glucose tolerance
Previous transient hyperglycemia that occurred either spontaneously or in response to specific stimuli but presently testing NORMAL
Glycogenolysis
Process that converts glycogen to glucose.
Steroids
Progesterone Estrogen Androgens Mineralocorticoids Glucocorticoids
Beta cells
Proinsulin
Secondary adrenocortical insufficiency
Results from any disorder of the hypothalamus or A.P. decreases Cortisol only so there is no hyperkalemia
Chronic complications - Infection
Sensory impairment, hypoxia (glycosylated RBCs), increased pathogens like glucose, decreased blood supply, abnormal WBCs
Delta cells
Somatostatin (stress insulin and glucagon)
How are steroids synthesized?
Steroid hormone synthesis occurs in the adrenal gland; the zona glomerulosa produces the mineralocorticoid, aldosterone, in response to stimulation by A-II; the zona fasciculate produces the glucocorticoid, cortisol, in response to stimulation of ACTH from the pituitary gland; the zona reticularis produces the androgen, DHEA. All of these hormones are synthesized from cholesterol
Hormonal regulation of glucose metabolism - Gastric Inhibitory Peptide (GIP)
Stimulates insulin release
Amines
T3/T4, Epinephrine, norepinephrine, Melatonin
HYP____A.P.____Thyroid_____
TRH, TSH, T3/T4
How do target cells regulate their responsiveness to endocrine hormones?
Target cells are able to regulate their responsiveness to hormones by altering the receptor number, affinity, and efficiency of coupling to intracellular responses
What are the differentiating characteristic of type 1 and type 2 diabetes?
The differentiating characteristic in type 1 diabetes is the destruction of the β cells of the pancreas that leads to an absolute insulin deficiency. Type 2 diabetes is characterized by a resistance to the action of insulin on peripheral tissues and a relative lack of insulin secondary to β-cell dysfunction
Which hormones are involved in regulation of serum glucose, and under what physiological conditions would each be secreted?
The ingestion of nutrients stimulates the release of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) from cells in the gut. Both hormones stimulate production and release of insulin and amylin. In the fasting state, the fall in insulin levels and stimulation of glycogenolysis causes the secretion of glucagons, along with other counterregulatory hormones, such as corticosteroids, growth hormone, and catecholamines
Primary hypothyroidism
The most common cause in the US is Hashimoto thyroiditis. It is characterized by decreased thyroxine (T4) and increased TSH (lack of feedback inhibition).
What are the normal actions on target cells of antidiuretic hormone, growth hormone, thyroid hormone and steroid hormones?
The primary targets for ADH are vasopressin 2 receptors on the basolateral membrane of distal renal tubule cells. ADH causes pores, called aquaporins, to move from the cytoplasm to the cell membranes of apical tubular epithelial cells which allow free diffusion of water from the tubular fluid into the cell. Growth hormone affects liver metabolism and also induces the production of IGF-1, which increases the growth of bone and cartilage tissues of the body. Thyroid and steroid hormones diffuse through their target cell membranes and bind with their respective cytoplasmic receptors. The hormone-receptor complex rapidly translocates into the nucleus where it binds to specific DNA sequences to alter responsive genes—many of which influence metabolism
How does the lipid or water solubility of hormones affect their transport in the circulation?
Thyroid and steroid hormones are lipid-soluble molecules that dissolve poorly in blood and require transport proteins (globulin) to convey them through the circulation. Water-soluble hormones are easily transported through the circulation to target cells and travel free in solution in the plasma
lipid soluble hormones
Thyroid hormones and steroids
FXN of insulin
To increases the rate of glucose transport into certain cells of the body.
Lipid soluble
Tyrosine-derived thyroid hormones (T3/T4) & steroids (sex hormones, glucocorticoids, and mineralocorticoids) -intracellular
Chronic complications - Macrovascular disease
Unrelated to the severity of disease - causes much morbidity & mortality; glycosylated end products & high serum lipids cause atherosclerosis - ischemia -coronary artery disease -stroke -peripheral arterial disease
malaise
a vague feeling of physical discomfort or uneasiness
Addisonian crisis/acute adrenal insufficiency may occur b/c
acute withdrawal of corticosteroids or due to periods of stress or trauma
Hypercortisolism (primary)
adrenocortical hyperfunction due to disease of the adrenal cortex (adrenal adenoma)
Tx of thyroid storm
aggressive management to achieve metabolic balance antithyroid drugs are given followed by iodine administration beta-blockers to alleviate symptoms antipyretic therapy fluid replacement glucocorticoids
Signs and symptoms of DM
always tired, crave extra liquids, frequent urination, numbness and tingling of feet, always hungry, unexplained weight loss, blurred vision, sexual dysfunction.
Grave's Disease/ hyperthyroidism
an autoimmune disorder characterized by the excessive production of thyroid hormones
The pathogenesis of Graves disease
antibodies mimic TSH by binding to and activating TSH receptors
Pathogenesis of DM - Viruses
are considered initiating factors in autoimmune cause of type 1 diabetes
hyperthyroidism ( primary)
autonomous
Hypothyroidism
congenital or acquired
congenital hypothyroidism
cretinism; effect of a lack of thyroid hormone during embryonic development or early childhood; causes neurologic defects, short stature & facial deformities
Secondary hypothyroidism is caused by
defects in TSH production and can result from: severe head trauma cranial neoplasms brain infections cranial irradiation neurosurgical procedures
Clinical manifestations of Cretinism
delayed bone maturation, puberty, mental retardation, an abdominal protrusion with an umbilical hernia
Hypercortisolism (exogenous)
disease caused by an ectopic ACTH producing tumor
Hypercortisolism (secondary)
disease caused by hyperfunction of the anterior pituitary ACTH-secreting cells
Hypercortisolism (tertiary)
disease caused by hypothalamic dysfunction or injury
Type 1 - Fasting blood glucose test
expected values: 70-120 mg/dl
Type 1 - Random blood glucose test
expected values: 70-120 mg/dl
Type 1 - urinalysis
expected values: negative for glucose.
Thyroid storm
form of life-threatening thyrotoxicosis that occurs when excessive amounts of thyroid hormones are acutely released into circulation
increased TSH causes thyroid cells to secrete large amounts of thyroglobulin, which leads to a
goiter
Acromegaly (A-A-A)
hypersecretion of GH during adulthood excess somatotropin (GH) after epiphyseal closure usually due to a pituitary adenoma
Gigantism
hypersecretion of GH in children and adolescents excess somatotropin (GH) before epiphyseal closure
Regulation of glucose Metabolism - Exercise
initially insulin levels drop and glucagon and catecholamine levels rise
Hypoadrenalism (Addison's disease)
insufficient adrenal hormones: chronic fatigue, m. weakness, loss of appetite, weight loss, low BP, dehydration, cardiac arrhythmias, bronzed appearance
Acute complications: Diabetic ketoacidosis
insulinopenia (in type 1) --> use of fatty acids from triglycerides as a major source of energy --> increase in fatty acid degradation --> increase in production of acetyl CoA --> increase in production of kept acids (ketone bodies) [acetoacetate, beta-hydroxybutyrate].
hypothalamic-pituitary dysfunction may result in
low levels of TSH and T4
Epsilon cells
make Ghrelin, which causes hunger.
How to diagnose Cushing Syndrome
measure 24 hr. urinary free cortisol, Dexamethasone suppression
hyperthyroidism (secondary)
mediation through stimulation of TSH receptors by substances such as TSH
steroid hormones (adrenocortical hormones)
mineralocorticoids (aldosterone) glucocorticoids (cortisol) adrenal androgen
Cushing Syndrome Clinical manifestation
moon face, weight gain, thin skin with purple striae, m. weakness, hyperglycemia, demineralization of bone, increased androgen production and emotional change
Hypothyroidism Tx
oral levothyroxine is used to replace or supplement hormone production IV levothyroxine used for myxedema coma
Peptides
oxytocin, ADH, ACTH, Calcitonin, PTH
what causes hyperthyroidism
pit adenoma thyroid carcinoma autoantibodies that bind and stimulate TSH receptors on the thyroid gland leading to diffuse toxic goiter ingestion of thyroid hormone preparations or excess iodides
GH is almost always due to
pituitary adenoma
Most hypothyroidism is primary or secondary?
primary
hyperthyroidism (Autoimmune)
related to TSH receptors antibodies
Complications of DM
retinopathy, nephropathy, neuropathy, angiopathy, infection, hyperlipidemia and atherosclerosis, hypoglycemia (insulin shock/insulin reaction, too much insulin), diabetic ketoacidosis (too little insulin), protein glycation
adrenal medulla
secretes catecholamines (epinephrine and norepinephrine)
adrenal cortex
secretes steroid hormones
Myxedema
severe or prolonged thyroid deficiency accumulation of glycosaminoglycans in interstitial spaces
Myxedema S/S
sluggishness, cool skin, increased cholesterol, medical emergency, not confused with old age
Graves S/S
suppressed TSH high T3/T4 warm pulsating goiter fine tremors exophthalmos, edema of orbit, extraocular m. weakness tachycardia
Hyperthyroidism TX
symptomatic relief: beta blockers reduce circulating hormones: methimazole, propylthiouracil more permanent tx: sx removal of thyroid, radioactive iodine
primary hyperthyroidism manifestation
undetectable TSH levels elevated serum T3 and T4