exam_4_20150304203013 Flashcards
Adrenal cortex secretes:
- zona glomerulosa: mineralocorticoids (aldosterone)2. zona faciculata: glucocorticoids (cortisol; corticosterone)3. zona reticularis: androgens and small amount of glucocorticoids
Adrenal Medulla is composed of what cells and secretes what
- chromaffin cells2. secrete epinephrine and norepinephrine
what is the function of the mineralocorticoids
- aldosterone is the most important and increases Na reabsorption from renal tubule and increases Na reabsorption form colonic fluid, saliva and sweat2. regulated by renin-angiotensin: angiotensin II binds to receptors in zona glomerulosa3. ACTH from ant pit has short term effects4. decreased levels of Na and increased levels of K stimulate synthesis
what is the function of glucocorticoids
- regulate metabolsim, fat, carbs, protein to maintain blood glucose levels: a. promotes degradation of muscle and adipose tissue and promotes uptake of amino acids and fatty acids by the liver for gluconeogenesis; b. mediates adaptation to stressc. down regulation of inflammatory and immune response: dysregulation of pro-inflammatory cytokine secretion and delays wound healingd. permissive to other metabolic processes2. regulated by a. ACTH which is regulated by CRH secreted by the hypothalamus; it is released episodically during day thus cortisol too; b.
ACTH
secreted episodically during day thus cortisol toosecreted in response to low levels of cortisolinhibited by increased levels of cortiosl and exogenous cortisolsecreted in response to stress (prolonged stress may abolish the normal diurnal rhythm of ACTH to cortisol
Androgen steroids
- function: stimulate protein synthesis (anabolic effects), influence development and growth of male sexual characteristics, and libido in women2. regulation by ACTH which stimulates secretion
catecholamines: norepinephrine and epinephrine
- function: signal fight or flight, interact with alpha and beta-adrenergic receptors, and increase contractility of cardiac and smooth muscle2. regulation: innervated by pre-ganglionic nerve fibers in SNS
cushing syndrome (hypercortisolims)
- etiology: a. exogenousIatrogenic Cushing Syndrome: administration of exogenous glucocorticoids results in hyposecretion of zona fasciculata and reticularis atrophy, loss of normal response to stressb. endogenousHypothalamic- pituitary cushing syndrome: association with hypersecretion of ACTH, most commonly an anterior pituitary ACTH producing adenoma: results in hyperplasia of ant pit; or can be caused by hypothalimic corticotropin releasing hormone (CRH) tumor->will have high cortisol levels and high ACTH levels Primary Adrenal Cushing Syndrome caused by adrenal gland function of ACTH is independent; hypersecretion of cortisol by adrenal adenomas or carcinomas; hypersecretion because cortical hyperplasia (rare); will have high cortisol levels and low ACTH levels Etopic Cushing Syndrome: secretion of ectopic ACTH by neoplasm, or ectopic CRH that cuases ACTH secretion
CRH
corticotropin releasing hormonesecreted by hypothalmusstimulates the synthesis and secretion of ACTH
Cushing Syndrome manifestations
- sx: central obesity, buffalo hump, moon facedecreased muscle mass and weakness, fragile thin skinabd striaecapillary fragility2. osteoprosis, HTN, decreased immune fxneuropsychiatric abnormalities like mood swings and depressionhirsutism and menstrual abnormalities3. lab: increased 24 hour cortisol levles, loss of diurnal rhythm of cortical secretions, hyperglycemia
Adrenocortical insufficiency etiology
primary acute adrenocortical insufficiency1. rapid withdrawal of long term steriod therapy; massive adrenal hemorrhage; stress in pts with underlying chronic adrenocortical insufficiencyprimary chronic adrenocortical insufficiency (Addisons Disease)2. autoimmune destruction of adrenal cortex; infections (tb, hiv), infiltrative disease (amyloidosis, cancer)
adrenocortical insufficiency manifestations
due to deficiency of glucocortidcoids and mineralocorticoidslethargy, weakness, GI (anorexia, n/v, wt loss), hypovolemia, hypotension, hyper-pigmentation with increased levels of ACTH (also leads to melanocyte-stimulating hormone (MSH) which causes abnormal skin darkening)LABS: hypoglycemia, hyperkalemia, hyponatremia, decreased cortisol levels, increased ACTH levels, inability of adrenal glands to produce cortisol in an ACTH stimulation test
Secondary Adrenocortical Insufficiency etiology
- pituitary or hypothalamic hypofunction
secondary adrenocortical insufficiency manifestations
- deficiency in glucocorticoids: decreased ACTH and endogenous crotisol levels; may also have decreased CRH levels in hypothalamic hypofunciton2. deficiency in androgens: alteration in male sex characteristics and decreased libido3. aldosterone secretion generally remains normal and no hyperpigmentation
hyperaldosteronism
- etiology: a. primary: autonomous overproduction of aldosterone adenoma (Conn syndrome) or cancer or genetic alterationb. secondary: increased secretion by overactivation of the renin-angiotensin system2. manifestations: hypernatremia, hypokalemia, HTN, muscle weakness, cardiac dysrhythmias, visual disturbances, Lab: primary: elevated aldosterone and depressed levels of reninsecondary: elevated levels of aldosterone and renin
hypoaldosteronism
- etiologya. primary: destruction of adrenocortical tissue or defects in synthesis b. secondary: low renin produciton or hypopituitarism2. manifestations: hyponatremia, hypovolemia, hypotension, hyperkalemia, impaired secretion of K in tubules leads to hyperkalemia elevatedc renin levels with destruction of adrenocortical tissue (primary)
Pheochromocytoma
- neoplasms composed of chromaffin cells that synthesize and release excessive amounts of catecholamines2. majority from adrenal medulla neoplasm3. can be genetic4. manifestations: HTN, tachycardia, palpitations, HA, sweating, tremor, anxiety, wt lo0ss, n/v, increased urinary excretion of free catecholamines5. complications: cardiac disease, cardiomyopathy, ischemia, arrhythmias; pulmonary edema, renal artery stenosis
hypothalamus anatomy
- parts surround the 3rd ventricle2. regulated by neural input from many parts of CNS and receives hormonal input from vasculature through fenestrated capillaries3. secretions to posterior pituitarya. oxytocin, antidiuretic hormone (ADH/vasopressin)to anterior pituitaryb. corticotropin releasing hormone (CRH) (stimulates ACTH), thyrotropin releasing hormone (TRH) (stimulates thyrotropin secreting hormone TSH), gonadotropin-releasing hormone (GnRH) (stimulates leutinizing hormone (LH) and follicle stimulating hormone (FSH)), growth hormone releasing hormone (GHRH) (triggers release of GH), prolactin releasing factor, growth inhibiting factor (somatostatin) (halts GH release), prolactin inhibiting factor (dopamine)
pituitary gland anatomy
- regulation by hormones from hypothalamus, negative feedback from circulating hormones2. posterior recieves a. oxytocin: smooth muscle contraction during breast feedingb. ADH: binds to receptors on cells in the collecting ducts of the kidney and promotes reabsorption of water back into circulation3. anterior contains 5 types of secretory cells which each type secrets one or more specific hormone; it receivesa. ACTH, TSH, GH, Prolactin (stimulates breast development and milk synthesis), gonadotropins (LH and FSH) (stimulates steriodogensis within ovaries (estrogen) and by the testes (testosterone)4. intermedia pituitary secretes malanocyte stimulating hormone MSH that increases skin pigmentation
hyperpituitarism of anterior pituitary
- etiology: hyperplasia, adenoma, or hypothalamus disorders2. patho of adenoma: usually composed of single cell type that produces an excess of one hormone (hormone overproduciton syndrome); usually well circumscribed but may infiltrate adjacent tissues; a. classificationsprolactin secreting (most common, causes amenorrhea, galactorrhea, infertility, loss of libido)GH: causes acromegaly/giantism3. manifestations: radiographic changes in sella turcia, visual field abnormalities from compression of optic nerve, sx from increased ICP: HA, n/v, change in LOC,endocrine abnormalities
hypopituitarism of anterior pituitary
- etiology: benign lesions, tumors, trauma, or infiltrative disorders or infection2. diseases of pituitary: nonfunctioning adenoma, ischemic necrosis (Sheehan syndrome: necrosis of anterior gland follwoing hypotensive epidsode during the peripartum period); infiltrativbe disorders, neoplasms, radiation, surgery, genetic3. manifestationsadrenal insufficiency, hypothyroidism, amenorrhea in women and infertility or impotence in men; other end organ deficiency syndromes
diabetes insupidus
- main characteristic: excessive urination when kidney does not reabsorb water in collecting duct2. etiologya. central: ADH deficiency: loss of cells in hypothalamus; from head trauma, tumor, inflammatory d/o, surgery, brain edemab. nephrogenic: renal tubular unresponsive to ADHc. pregnancy: placental release of excessive amts of vasopressinase3. manifestations: hypernatremia, increased urine output (diluted urine); polydipsia
syndrome of inappropriate ADH (SIADH)
- main characteristic: excessive secretion of ADH2. etiology: most commonly from secretion ectopically by malignant neoplasm; could be from injury3. patho: causes reabsorption of excessive amounts of water which results in manifestations of hyponatremia and neurologic dysfunction
cellular mechanism of hormone action is dependent on..
- cell sensitivity to a particular hormone is related to the total number of receptors per cella. cells can up-regulate or down-regulate the number of receptors2. water soluble hormones interact with cell membrane receptors3. lipid soluble hormones cross the cell membrane by diffusion and bind with receptors int he cytoplasm
pancreas islets of langerhans
- have three major typesa cells: glucagon secretingB cells: insulin secretingand somatostatin secreting2. cells are highly vascularized, allows regulation of secretory products and drains into protal vein and travels to liver
insulin structure and regulation
- structure: synthesized in B cells, active form is the a and b chain; inactive is the c-peptide-stored in secretory granules in B cells-secretion is pulsatile -preformed then newly formed if the stimulus persists-catabolized in liver (50% 1st pass)2. regulation a. metabolic: increased glucose stimulates release and increased amino acid food products stimulate releaseb. endocrine: indirectly stimulated by GH and thyroxine and inhibited by somatostatin, insulin, and catecholaminesc. neural: insulin release is enhanced by PNS and inhibited by SNS
insulin secretion
blood glucose increases=uptake of glucose by the GLUT-2 transporter->glycolytic phsphorylation of glucose causes a rise in ATP:ADP ratio=inactivates K channel that depolarizes membrane causes the Ca channel to open allowing Ca ions to flow inward->ensuing rise in Ca levels lead to exocytotic release of insulin from their storage granule
insulin mechanism of action in skeletal and adipose tissue
- skeletal and adipose tissue-insulin binds to “a” subunits on insulin receptors-auto-phosphorylation of b subunits activates tyrosine kinase in b subunits -tyrosine kinase: when activated initiates complex intracellular signalling pathways (P13-K pathway and MAP kinase pathway)-P13-k (phosphatidylinostil 3 kinase) pathway induces a glucose transporter (GLUT-4 transporter) to move to the cell surface to transport glucose across membrane; mediates glucose, fat and protein metabolism-MAP (mitogen activated protein) kinase pathway is involved in varios mitogenic cellular activites
insulin mechanism of action in liver
- promotes glucose uptake through GLUT-2 transporter -it is a membrane protein that allows two-way directional glucose movement
insulin mechanisms of action to brain
- insulin is not required for entry of glucose into other tissues including brain-GLUT-1 transporter allows glucose into other tissues including brain
Function of Insulin-Anabolic
-major sites of insulin action are in the liver, muscle and adipose tissue-prevents the breakdown and release of fuel that has already been stored aka inhibits catabolism-carbs metabolism: stimulates glucose uptake in muscles and adipose and promotes storage, stimulates synthesis of glycogen in liver and inhibits hepatic glucose fromation and glycogen breakdown-fat metabolism: insulin promotes fat storage and inhibits fat breakdown; stimulates lipogeneiss, inhibits the break down of fatty acids to glucose-protein metabolism: promotes synthesis of protein and inhibits protein breakdown from gluconeogensis
glucagon
- stucture: produced in “a” cells - extracted by liver on 1st pass, metabolized in liver and kidneys - regulation: inhibited by high glucose levels and/or insulin, fatty acids, and ketones- effect: maintain serum glucose levels: stimulates the breakdown of hepatic glycogen stores and hepatic glucose synthesis
somatostatin
-produced: by d cells-effect: inhibits both glucagon and insulin secretion as well as its own secretion
diabetes mellitus general information
dx: fasting blood glucose greater than 126 on more than one occasion-sx of dm plus a random plasma glucose greater than 200-a ploasma glucose greater than 200 2 hours after a standard oral glucose dose-A1c levle greater than 6.5%-pre: fasting of 100-125-insulin resistance: insulin levels can be measured a HOMA-IR of 2.8-3.0 is recommended as cut off point for insulin resistance to be used in clinical practice
type 1 DM
- age onset less than 302. genetic susceptibility: genetic mutation to loci that encodes class II MHC molecules; enviornmental factors (infection, lack of usual infections); autoimmune destruciton of B cells 3. patho: cell mediated response; failure of self tolerance in T cells; Th1 cells stiulate cytokine secretion and CD8 T cells mediated loss of B cells; humoral mediated response: autoantibodies against B cells and insulin-inflammatory response->macrophages activation and more cytokine->more B cell injury and necrosis (insulitis)=B cell apoptosis=islet atrophy and fibrosis, insulin deficiency, disease progression is gradual
type 2 DM
-occurs commonly in adults-genetic defects in genes important to B cell function and insulin secretion-enviornmental: physical and diet and obesity-patho: peripheral tissue insulin resistance and inadequate insulin secretion-decreased ability of peripheral tissues to respond to insulin->leads to decreased uptake of glucose in muscle and adipose tissue->reduced glycolysis->inability of insulin to suppress gluconeogenesis-functional defects in the insulin signaling pathway have been found-abnormality of insulin molecule, decreased number of insulin receptors, defective receptor activity, problems alon intracellular insulin signaling pathways, problems with GLUT-4 transporter-role of obesity: increased levels of intracellular triglycerides and free fatty acids metabolism inhibit insulin signaling and free fatty acids induce secretion of inflammatory cytokines; dysregulation of adipokines which are insulin sensitizing (leptin, adeponectin)-inadequate insulin secrection: B cell dysfunction (hypersecretion: insulin secretion is intially higher for each glucose molecule relative to normal and then B cell hyperplasia to support this level of insulin hypersecretion); B cell exhaustion causes early failure and loss of pulsatile effect and hyposecretion of insulin and eventually B cell failure-B cell loss: lipotoxicity from high levels of free fatty acids induces apoptosis and glucotoxicity from hyperglycemia forms excessive ROS that continually bombards and damages the B cell (thought to alter genes that produce insulin so that insulin molecule formed is abnormal); islet cells are usually at risk for damage by pro-oxidant forces as they do not manufacture much antioxidant -apoptosis, islet degeneration and deposition of amyloid-usually basal level is produced for first 10-15 years until it stops
gestational DM
-2nd half of gestation and tends to resolve with delivery-risk fx: family hx of dm, obesity, higher maternal age-dx by 2 part glucose challange test1. resistance pregnancy hormones and other fx are thought to interfere with action of insulin as it binds to insulin receptors2. impaired secretion: women with GDM have abnormalities in insulin secretion possibly decreased pancreatic beta cell reserve3. increased hepatic glucose production: increased levels of progesterone, cortisol, prolactin and chorionic somatomammotropin stimulate glucogenolysis, and gluconeognesis
manifestations of DM
hyperglycemia, glucosuria, polyuria, polydipsia, polyphyagia, increased levels of glucagon, ketosis (from lipolysis of fat stores), elevation of VLDL (increased fatty acids from increased lipolysis), negative nitrogen balance and muscle wasting
acute complications of DM
predisposing factors of stress, infections, trauma, or not taking medications can result in DKA-in adipose tissue: increased lipolysis with release of fatty acids, free fatty acid uptake by liver, hepatic mitochondria conver acetyl-COa to ketone bodies, -in liver: increased protein catabolism with release of amino acides, amino acid uptake by liver and produciton of fatty acids and ketoacids -ketones/ketoacids deplete buffering systems which results in systemic acidosis -KDA-manifestations: severe hyperglycemia, increased serum osmolality from polyuria, increased ketones and ketonurea (metabolic acidosis, kussmaul breathing, fruity breath), low Na from osmotic diuresis, normal to elevated K from shift of K out of cell, n/v, abd pain, coma (plasma osmolality reaches 340 mosm/L)-Hyperglycemic hyperosmolar nonketotic state (HHNK) occurs with type 2, hyperglycemia with sever dehydration that produces hyperosmolar state usually absence of ketoacidosis becasue these individuals have enough ensulin to prevent ketogenesis -mainfestations: coma, increased glucose, life-threatening-hypoglycemia
chronic complications of DM
-advanced glycosylation end (AGE) products: from direct action of sugars on protein, process of AGE fromation (first reacts reversibly with amino acids on ceullular proteins to form an unstable intermediate (Schiff base); the unstable intermediate undergoes futher rearrangement to form a more stable intermediate and when this occurs with RBCs its called HbA1C; the stable intermediate undergoes further reactions to form an irreverisble advanced glycoslation end produce (AGE))-results in release of pro inflammatory cytokines and growth factors from macrophages, increased pro-coagulant acitivty, generation of ROS, proliferation of vascular smooth muscle and synthesis of extracellular matrix and abnormal crosslinking of exctracellular matrix proteins=vascular stiffness,traps nonglycated plasma and interstitial proteins-pathways: polyol (sorbital) pathway normal: enzymatic process uses cofactor (NADPH which is required to manufacture gluthiaone hyperglycemia: excess intercellular sorbital results in injury; consumption of NADPH results in decreased manufacture of gluthiaone =ROS injury primary tissue effected is nerves, lenses, kidneys, blood vessels-pathway protein kinase C pathway protein C is a protein involved in controlling other proteins intracellular hyperglycemia stimulates more DAG formation which stimulates more protein kinase C productions = stimulates the production of endothelial growth factor which stimulates neovascularization=produces profibrinogenic molecules leading to increased deposition of exctracellular matrix capillary basement membrane material=stimulates releae of proinflammatory cytokines=ROS injury = Imparied NO produciton -pathway Hexosamine works to turn off the insulin signalling thus induces insulin resistance and stimulates production of protein such as transforming growth factor=microvascular damage and increased expression of inflammatory cytokines= ROS damage
retinapothy from DM
capillary endothelial cell damage and basement membrane thickening->macular edema and retinal ischemia->retinal ischemia and/or protein kinase C->growth factors->neovascularizaiton-nonproliferative process: vessels abnormal (increased tortuosity, dilation), microaneurysms (tiny dots), increased vascular permeability (macular edem)-preproliferative process: cotton wool spots from infarcts o nerve fibers layer secondary to retinal ischemia-proliferative process: neovascularization, angiogenesis of vessels results in hemorrhage, retinal detachement, neovascular glaucoma
nephropathy from DM
patho: AGE or sorbital products and activation of protein kinase Cmanifestations: microalbuminemia to macroalbuminuria
atherosclerosis in DM
-macroangiopathy-premature atherosclerosis-increased triglycerides, VLDL, LDL in circulation and increased trapping of LDL-microangiopathy: diffuse thickening of basement membranes and thickening is predominantly of the IV collagen
HTN in DM
from alterations in fibrin, collagen, elastin in arteries secondary to AGE and from ROS damage to endothelial cells which alter vessel function (impairs NO formation and stimulates endothelin)
Neuropathy in DM
excess glucose->shunted along metabolic pathways->ROS->neuronal injury which impairs nerve function, conduction, can cause neuronal cell death and also due to cell injury secondary to changes in microcirculation, occurs in peripheral nerves and autonomic nervous system
risk of infection in DM
do to decreased polymononuclear (granulocyte) function: decreased luekocyte adherence, decreased chemotaxis, decreased phagocytosis, decreased antioxidant acitvities; because AGE alteration to circulation plasma proteins
exercise and insulin resistance
stimulates distinctively separate set of GLUT-4 transporters through a separate cellular signaling pathway to move to muscle cell membrane for glucose transport
structure of thyroid gland
contains follicles that contain colloid (contains stored thyroid hormones)parafolliculuar cells are scattered between (C-cells)
regulation of thyroid secretions
- stimulations: iodide uptake, throglobulin synthesis, T3 and T4 secretion, 2. inhibition: negative feedback loop, circulating T3 and T4 inhibits TSH secretion and TRH secretion directly(TRH indirectly inhibits TSH by this)
Thyroid hormones
- majority of t3 and t4 is reversibly bound to plasma protein for transport-free portion is the active portion (t3 is more active than t4)-t4 serves as a prohoromone for t3-t3 has grewater affinity for target cell receptor sites than t42. effects: increases BMR, heat production, and stimulates o2 consumption-promotes bone and brain growth and development-increases rate of carb absorption, protein synthesis, and lipid catabolism-stimulates the nervous system and cardiac rate and contractility