Midterm #3 Flashcards

Question

hypothalamus and pituitary: negative feedback

Answer 1

* hormone from peripheral gland (ex: cortisol) bind in pituitary and hypothalamus and inhibit tropic hormone secretion (ex: CRH (corticotropin releasing hormone) and ACTH (adrenocorticotropic hormone)) * Less CRH leads to less ACTH which leads to less cortisol secretion (in zona fasiculata of adrenal cortex) * "hormonal homeostasis" *

Answer 2

* hypersecretion of cortisol * central obesity, insulin resistance, bone reabsorption (osteoporosis), and hypertension * tumor in adrenal cortex * increased negative feedback from cortisol * ACTH is low *

Answer 3

* cortisol hypersecretion * central obesity, insulin resistance, bone reabsorption (osteoporosis), and hypertension * pituitary adenoma * ACTH and cortisol levels high

Answer 4

* hyposecretion of cortisol * problem originates in adrenal gland * damage to adrenal cortex, hyposecretion of aldosterone (regulate K and Na in ECF) * hyposecretion of coritsol AND aldosterone is **Addison's Disease** * high levels of ACTH

Answer 5

* hypopituitary adrenal insufficiency * low ACTH levels lead to hyposecretion of cortisol * can occur after the end of high dose glucocorticoid therapy

Answer 6

* glucocorticoid is the name for a molecule that is a glucocorticoid receptor agonist; the glucocorticoid receptor is the receptor for cortisol * Chronic high levels of glucocorticoids lead to a suppression of ACTH secretion * glucocorticoid therapy is discontinued, the result is hypocortisolism * avoid with alternate day dosing or taper off

Answer 7

* First establish hypercortisolism * roughly circadian pattern in which cortisol secretion is at its lowest around midnight, thus cortisol levels are measured at this time * level of ACTH is used to distinguish between primary hypercortisolism and Cushing's disease due to a pituitary adenoma

Answer 8

* Primary adrenal insufficiency * autoimmune cause, but can also result from tuberculosis * affect both the zona glomerulosa and the zona fasciculata, so there is hyposecretion of both cortisol and aldosterone * increased ACTH secretion * challenge test to diagnose: * determines the ability of the adrenal gland to respond to exogenously administered ACTH with increased cortisol secretion

Answer 9

* Secondary adrenal insufficiency * consequence of medical therapy with glucocorticoids

Answer 10

* function kidney unit: nephron * filtration * bulkflow of water and small molecules into Bowman's capsule * glucose, amino acids, and certain ions end up in the forming urine * cells lining the kidney tubules transfer these substances out of the forming urine and back into the extracellular fluid. This process is known as reabsorption * normal circumstances, 100% of the glucose that is filtered is reabsorbed * Glucose reabsorption involves transport proteins that require **specific binding** * diabetes, transporter becomes saturated * glucose draws water via osmosis

Answer 11

* SGLT2 inhibitors * inhibiting the sodium-glucose cotransporter (SGLT2) that is specific to the kidney tubules and responsible for 90% of glucose reabsorption * reduce hyperglycemia and promote weight loss * increase urine flow, but not to bothersome point * independent of insulin, can be used in combo with other drugs * "-gliflozin" * Canagliflozin (tradename: Invokana) * Dapagliflozin (tradename: Forxiga) * Empagliflozin (tradename: Jardiance)

Answer 12

* measures the percentage of glycosylated hemoglobin * will be higher if there have been more periods of hyperglycemia in the recent past * HbA1c of 6.5% or greater is diagnostic for diabetes mellitus * no fasting, can be done at any time of day

Answer 13

* morning when not eaten for 8 hours *

Answer 14

* how body responds to glucose * 75 grams of glucose * Reflects two things: * ability of the beta cells to secrete insulin * responsiveness of cells in the body to insulin * Diabetes indicated by: * fasting plasma glucose above 126 mg/dL * a 2-hour reading greater than 200 mg/dL

Answer 15

* impaired glucose homeostasis * fasting glucose that is greater than 100 mg/dL is categorized as having impaired fasting glucose * impaired glucose tolerance, which involves a 2-hour reading of greater than 140 mg/dL

Answer 16

* insulin secretion * initially compensate by secreting more insulin, Hyperinsulinemia * relative insulin deficiency when the beta cells can no longer produce enough insulin to compensate

Answer 17

* more visceral adipose tissue * higher rates of lipolysis in visceral adipocytes, resulting in higher levels of circulating fatty acids * higher rates of lipolysis in visceral adipocytes, resulting in higher levels of circulating fatty acids * ectopic lipid interefers with insulin sensitivity * **Reduced insulin signal transduction**: Fatty acids activate serine-threonine kinases that phosphorylate insulin receptor substrates on different amino acids, inhibiting tyrosine phosphorylation by the insulin receptor. Insulin receptor is a tyrosine kinase * **Altered metabolism: **Fatty acids stimulate gluconeogenesis in the liver. Thus hepatic glucose production, which should be inhibited by insulin, persists. * **Increased inflammation: **saturated fatty acids stimulate the innate immune system

Answer 18

* Adiopoctes secrete regulatory molecules known as **adipokines.** * **Inflammatory paracrines:** TNF-alpha and IL-6, interfering with insulin signal transduction, promoting inflammation in blood vessels * **Decreased adiponectin: **secretion is decreased in obesity, increases insulin sensitivity and improves metabolism by stimulating fatty acid oxidation * **Increased cortisol: **post-absorptive state hormones that decrease responsiveness to insulin, Adipocytes have an enzyme that converts an inactive cortisol metabolite back into active cortisol *

Answer 19

* venous blood that drains visceral adipose tissue in the mesenteries flows first to the liver via the hepatic portal vein, before returning to the heart * changes in regulatory molecules caused by visceral adipocytes are in a position to directly affect the liver, a key target of insulin.

Answer 20

* obesity is associated with a state of chronic low-level inflammation * higher number of macrophages * release inflammatory paracrines that cause insulin resistance.

Answer 21

* Weight loss improves insulin sensitivity * negative feedback loop involving the hormone leptin which works to maintain body weight at a set point * obese individuals, this negative feedback loop works to maintain body weight at a higher than normal set point * lose weight, lose leptin, hunger and lower energy expenditure

Answer 22

* Roux-en-Y gastric bypass: smaller stomach, limit nutrient absorption through bypass of the initial part of the small intestine (malabsorption) * weight loss and insulin resitance resolution * reorganization of the digestive tract somehow alters the secretion of regulatory molecules that influence insulin sensitivity

Answer 23

* promotes glucose uptake in skeletal muscle * promotes the movement of glucose transporters to the muscle cell plasma membrane, and it does so independently of insulin * weight loss

Answer 24

* MOA not completly understood * affects mitochondrial function in hepatocytes. * outcome of these effects in liver cells is the inhibition of gluconeogenesis

Answer 25

* TZD's: agonists for the intracellular receptor known as PPAR-gamma * expressed in adipocytes and pre-adipocytes * transcription factor, stimulating adipocyte differentiation andlipogenesis (triacylglycerol formation) in adipocytes * large, hypertrophic adipocytes are the most problematic), and in part on the increased fatty acids in the circulation * TZD's stimulate the formation of greater numbers of small adipocytes, and stimulate apoptosis in hypertrophic adipocytes * promote fat storage in adipocytes, thus decreasing the level of circulating fatty acids and preventing the pathological effects of lipid accumulation in other tissues (ectopic lipid) * adipocytes to increase expression of adiponectin, which promotes insulin sensitivity * Use restricted because of safety concerns

Answer 26

* glycemic control, that is the prevention of hyperglycemia * Chronic hyperglycemia leads toabnormal glycoslyation * Diabetic Complications: * Cardiovascular Disease * Nephropathy * Retinopathy * Peripheral neuropathy * Foot ulcers * adverse effect of more intensive diabetic therapy is hypoglycemia * Glycemic control monitored through HbA1c, or thepercentage of glycosylated hemoglobin * detects glycemic control in the previous 4-8 weeks * recommends an HbA1c target of less than 7% for most diabetics

Answer 27

* necessary for type 1 diabetics * absolute insulin deficiency due to the autoimmune destruction of the pancreatic beta cells * also in T2DM * later on, beta cells damaged by hyperglycemia *

Answer 28

* increase insulin secretion * bind to and block the ATP-sensitive K+ channel on pancreatic beta cells * depolarization * cause weight gain * Sulfonylureas (glyburide, tolbutamide) are older drugs and less expensive * Risk of hypoglycemia * meglitinides (repaglinide, nateglinide) are newer drugs that are designed to avoid this problem * shorter half-life * taken at mealtimes to enhance insulin secretion and prevent postprandial hyperglycemia.

Answer 29

* increase insulin secretion * GLP-1 agonists are peptide drugs with a longer half-life than the native hormone because they are resistant to digestion by the protease DPP-4 * DPP-4 inhibitors ("gliptins") prolong the action of native incretins * less effective at lowering HbA1c than GLP-1 agonists, but an advantage is that they are oral drugs. * GLP-1 agonists induce weight loss * delays stomach emptying * feel full sooner

Answer 30

* insulin sensitizers * first drug of choice used to treat newly diagnosed diabetes * pre-diabetics * liver, where metformin inhibits gluconeogenesis.

Answer 31

* Insulin sensisitzer * pioglitazone, rosiglitazone * agonists for an intracellular receptor known as PPAR-gamma * expressed in adipocytes, * affect adipocyte gene expression, ultimately causing decreases in circulating fatty acids * affect adipocyte secretion of regulatory molecules * adipocytes secrete more adiponectin, which increases insulin sensitivity, and fewer adipokines that cause insulin resistance. * Safety concerns * rosiglitazone (trade name: Avandia) to increased risk of heart attack * pioglitazone (trade name: Actos) * weight gain and increased fluid retention, and increase the risk for heart failure * may be possible to develop PPAR-gamma receptor modulators. The hope is to develop drugs that are insulin-sensitizing without causing adverse effects that increase the risk for cardiovascular disease

Answer 32

* Glucagon is secreted by the alpha cells in the pancreatic islets of Langerhans * post-absorbative hormones * stimulate hepatic glucose production * Glucagon secretion can be higher than normal, particularly in type 1 diabetes mellitus * GLP-1 agonists * pramlintide, a synthetic analogue of the peptide hormone amylin, which is produced by the pancreatic beta cells * inhibits glucagon secretion and also slows stomach emptying * adjunct drug

Answer 33

* SGLT2 inhibitors * improve glycemic control and cause weight loss * canagliflozin, dapaglifolozin, and empagliflozin * ower blood glucose through a mechanism that is independent of insulin, so they could be safely combined with other treatments.

Answer 34

* Leptin participates in a negative feedback loop that regulates the amount of energy stored in adipose tissue (adiposity), which is a major determinant of body weight * Leptin is transported into the brain, primarily acting on neurons in the hypothalamus * decreased energy intake (feeding) * NOT a satiety signal * increases metabolic rate

Answer 35

* homozygous mutant mice completely lack leptin * eat constantly, obese , DM from insulin resistance, infertile * leptin injections cause weightloss * human obesity NOT from leptin deficiency * leptin only cause weight loss at high doses * may be leptin resistant

Answer 36

* scarcity of food more evolutionarily important * decreased leptin increases hunger and decreases metabolic rate * leptin administration after weightloss to maintain weight loss

Answer 37

* degeneration of adipose tissue and insulin resistance * lipodystrophy results in decreased leptin secretion because there is decreased adipose tissue. * Leptin treatment improves insulin sensitivity in patients with lipodystrophy.

Answer 38

* Thyroid hormone has a crucial role in the development of the nervous system, being involved in the growth of synapses and the formation of myelin * **Endemic cretinism** is a disorder of cognitive development with reduced physical growth that occurs if thyroid hormone is deficient during gestation and early post-natal life * making sure that pregnant women have sufficient iodine in their diet to be **euthyroid** (having adequate thyroid hormone levels) * **Goiter** * low level of iodine in the diet, then less active T3 and T4 can be synthesized * reduced negative feedback inhibition of secretion of the tropic hormones, TRH (thyro ropin releasing hormone; released by the hypothalamus) and TSH (thyroid stimulating hormone or thyrotropin; released by the anterior pituitary) * TSH stimulates proliferation of follicle cells * individuals may have goiter and yet be euthyroid, because the enlarged thyroid gland is better able to use the limited amount of iodine available

Answer 39

* most common cause of hyperthyroidism * agonist antibodies are produced that bind to the TSH receptor * synthesis of T3 and T4, and proliferation of follicle cells * levels of TRH and TSH decrease, but this does not decrease thyroid hormone production because the stimulation of the thyroid gland is independent of TSH * Symptoms: * heat intolerant * tachycardia (fast heart rate) * thyroid hormone affects expression of cardiac ion channels and contractile proteins so that the force and rate of the heart beat are both increased * thyroid hormone increases the responsiveness to epinephrine and norepinephrin * nervousness, sweating and increased heart rate * beta-adrenergic antagonists may be used to relieve symptoms. * removed surgically (thyroidectomy) * drugs that inhibit thyroid hormone synthesis * administer radioactive iodine *

Answer 40

* most common cause of hypothyroidism in the United States * autoimmune destruction of the thyroid gland * antibodies to thyroid antigens, as well as infiltration by cytotoxic T cells lead to destruction * may initially develop goiter, (which occurs due to inflammation), rather than symptoms due to hypothyroidism * thyroid gland stores large amounts of thyroid hormone as thyroglobulin * As the store of thyroid hormone decreases, negative feedback inhibition decreases and TSH levels will rise * Symptoms: * decreased metabolic rate * gain weight * feel sluggish and cold * slowed heart rate * replacement therapy with thyroxine (T4).

Answer 41

* proliferation (hyperplasia) * increase in cell size (hypertrophy) * cell size is limited by limitations in the distance of diffusion, so most growth occurs by an increase in cell number

Answer 42

* adequate nutrition * appropriate endocrine regulation * natural measure of the growth that occurs during childhood is the eventual height attained, or stature * function of growth by the long bones in the body, *

Answer 43

* long bones form by a process that is known as endochondral ossification * mesenchymal cells condense and then differentiate as chondrocytes to form a cartilage model of the bone * Mesenchymal cells are the developmental precursors of connective tissue cells * cartilage model is replaced by bone * first, shaft is ossified * chondrocytes enlarge and change, and blood vessels penetrate into the tissue, carrying bone precursor cells (osteoblasts) that secrete bone matrix * Ossification of the shaft spreads outwards towards the epiphyses (ends of bone) * Secondary ossification centers eventually appear in the epiphyses * all cartilage replaced by bone except for at epiphyseal growth plate.

Answer 44

* stimulation of chondrocyte proliferation at the epiphyseal growth plates * keep growing if cartilage proliferation keeps pace with the rate of ossification * gonadal steroids (estrogen, testosterone) cause closure of the epiphyseal growth plates

Answer 45

* key endocrine regulator of postnatal growth is **growth hormone (GH)** * secreted by cells in the adenohypophysis * GH indirectly stimulates growth at the epiphyseal plate * GH stimulates production of insulin-like growth factor-1 (IGF-1) * IGF-1 is hormone and paracrine * some in liver and to bone via circulation * some produced locally by chondrocyte cell * IGF-1 tdirectly stimulates chondrocyte cell division and bone growth * Regulation of GH secretion * hormones that are secreted by parvocellular cells in the hypothalamus * both a stimulatory hormone,growth hormone releasing hormone (GHRH) and an inhibitory hormone, somatostatin * Thyroid hormone is important for growth because it promotes growth hormone synthesis. * Gonadal steroids (estrogen and testosterone), whose secretion increases at puberty, initially promote growth by increasing GH secretion, and then subsequently cause growth to end by causing the closure of the epiphyseal growth plates. * Cortisol, which is released in response to stress, causes an inhibition of growth.

Answer 46

* Short stature * defect in GH secretion (growth hormone deficiency) * treated with GH replacement * defect in the growth hormone receptor (growth hormone resistance) * Laron dwarfism * treated with IGF-1 replacement * Hypersecretion of GH by a pituitary tumor * Childhood: gigantism, rare * Adulthood: acromegaly * insidious onset b/c of slow growing tumor * High levels of GH and IGF-1 cause excessive growth of soft tissues and appositional growth in certain bones, particularly the jaw and skull, leading to disfiguring facial changes * insulin resistance and lipid disorders * heart disease and arthritis * Treated with surgery to remove tumor * **somatostatin agonist**, such as **octreotide**

Answer 47

* regulation of the concentration of calcium ions in the extracellular fluid [Ca++]_ECF * stabilizing effect on voltage-gated ion channels * (hypocalcemia), voltage-gated ion channels start opening spontaneously * nerve and muscle cells to become hyperactive * muscle spasms, hypocalcemic tetany * (hypercalcemia), voltage-gated ion channels don't open as easily * depressed nervous system function * deposits of calcium phosphate (stones) in blood vessels and in the kidneys.

Answer 48

* parathyroid hormone (PTH) * major regulator * secretion is stimulated by hypocalcemia * stimulates the release of Ca++ from bone, in part by stimulating bone resorption. * decreases urinary loss of Ca++ by stimulating Ca++ reabsorption * indirectly stimulates Ca++ absorption in the small intestine by stimulating synthesis of 1,25(OH)2D in the kidney * 1,25(OH)2D (the active form of vitamin D) *

Answer 49

* rapid effect * stimulates osteoblasts to pump Ca++ ions out of the fluid surrounding the bone (which has a higher Ca++ concentration) and into the ECF * long term effect * stimulates bone resorption * osteoblasts that express PTH receptors * PTH stimulation of osteoblasts causes them to express a signaling molecule that activates osteoclasts

Answer 50

* decreases the loss of Ca++ ions in the urine by stimulating Ca++ reabsorption * also inhibits phosphate reabsorption in the kidney. * stimulate production of 1,25(OH)2D * A precursor (known specifically as vitamin D3 or cholecalciferol) is synthesized in a photochemical reaction in the skin, in response to sunlight * chemically modified in the liver to form 25-(OH)D. * enzyme in the liver is constitutively active, meaning it is always working * kidney enzyme is regulated * PTH is to stimulate the regulated kidney enzyme * resulting in the production of 1,25(OH)2D. * 1,25(OH)2D works in the small intestine to promote Ca++ absorption * kidney disease, inadequate amounts of 1,25(OH)2D * Ca++ homeostasis is maintained at the expense of bone * [Ca++]ECF drops because of a lack of Ca++ absorption from the diet * stimulates high levels of PTH secretion * secondary hyperparathyroidismbecause the problem that causes the hyperparathyroidism is in the kidney * treated by administering vitamin D and Ca++ supplements * cinacalcet, calcimimetic drug that binds to the Ca++ receptor on cells in the parathyroid gland, inhibiting the secretion of PTH.

Answer 51

* Bone remodeling is triggered by a need for calcium in the extracellular fluid * mechanical stresses as well * Osteoblasts * bone-forming cells * onnective tissue cells found at the surface of bone * can be stimulated to proliferate and differentiate as osteocytes * Osteocytes * bone cells * manufacture type I collagen and other substances that make up the bone extracellular matrix * found enclosed in bone. * Osteoclasts * bone-resorbing cells * large, multinucleate cells that form through the fusion of precursor cells * Unlike osteoblasts, which are related to fibroblasts and other connective tissue cells, osteoclasts are descended from stem cells in the bone marrow that also give rise to monocytes.

Answer 52

* can be triggered by parathyroid hormone (PTH) in response to hypocalcemia * PTH stimulates the generation of new osteoclasts (osteoclastogenesis) * mature osteoclast needs to tightly adhere to the bone, creating a specialized isolated compartment * membrane adjacent to the bone differentiates as the ruffled membrane * contains proteins that acidify the compartment adjacent to the bone * acid dissolves the minerals in the bone; subsequently, digestive enzymes break down type I collagen and other proteins * Bone resorption ends when the osteoclast dies by apoptosis.

Answer 53

* Receptors for PTH are located on osteoblasts, which then signal to bone marrow-derived osteoclast precursors to stimulate their fusion, differentiation and activation * Osteoclast precursors express a cell-surface receptor known as RANK * Osteoblasts express RANKL * stimulated by PTH, osteoblasts up-regulate expression of RANKL, which binds to RANK, activating signaling pathways that promote osteoclast differentiation and survival. * Osteoblasts also express a secreted factor called osteoprotegerin * "protects bone" by preventing bone resorption * decoy receptor for RANKL: it binds RANKL and therefore prevents binding to RANK and stimulation of osteoclastogenesis * ratio of osteoprotegerin:RANKL produced by osteoblasts will determine the extent of bone resorption. * Denosumab * monoclonal antibody that binds to RANKL * treatment of osteoporosis

Answer 54

* severe reduction in bone mass that substantially increases the risk of bone fracture * Partial reduction of bone mass is referred to as osteopenia. * Someone with a low peak bone mass is more likely to develop osteoporosis later in life * peak in 30's * genetics, nutrtion, exercise * calcium, vitamin D, and exercise in bone building years * Hypersecretion of PTH, thyroid hormone, and cortisol all promote bone loss * gonadal steroids (estrogen and testosterone) have a key role in maintaining skeletal mass * suppressing the production of signals that promote osteoclastogenesis

Answer 55

* treatments for osteoporosis areantiresorptive * inhibit osteoclasts * reduce bone loss, but they do not work to build new bone *

Answer 56

* used to be mainstay of treatment * greater risk of adverse cardiovascular events, as well as an increased risk of breast cancer *

Answer 57

* first line of therapy for osteoporosis * non-hormonal drug therapy * related to pyrophosphate * inhibiting osteoclast activity and inducing osteoclast apoptosis * alendronate and risedronate. *

Answer 58

* Selective Estrogen Receptor Modulator * bind to estrogen receptors, acting as estrogen agonists in some tissues, while acting as estrogen antagonists in other tissues * avoid the adverse effects of administering estrogen, while at the same time gaining the beneficial effect of estrogen on bone health * raloxifene

Answer 59

monoclonal antibody that binds to RANKL to inhibit osteoclastogenesis. Denosumab mimics the effect of the endogenous protein osteoprotegerin.

Answer 60

* peptide analog of PTH * only FDA-approved treatment for osteoporosis that is anabolic * stimulates osteoblasts to build new bone * intermittent treatment with PTH actually stimulates bone deposition * promoting osteoblast survival, or by stimulating osteoblast proliferation * present chronically, PTH causes bone resorption * once-daily injection

Answer 61

* acts oppositely to PTH * osteoporosis treatment * calcitonin secretion is stimulated by hypercalcemia and it acts to reduce calcium in the ECF * binds to receptors on the osteoclast and inhibits bone resorption * peptide hormone * injection or nasal spray

Midterm #3 Flashcards

(89 cards)