exam_4_20150304203013 Flashcards
1
Q
Adrenal cortex secretes:
A
- zona glomerulosa: mineralocorticoids (aldosterone)2. zona faciculata: glucocorticoids (cortisol; corticosterone)3. zona reticularis: androgens and small amount of glucocorticoids
2
Q
Adrenal Medulla is composed of what cells and secretes what
A
- chromaffin cells2. secrete epinephrine and norepinephrine
3
Q
what is the function of the mineralocorticoids
A
- 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
4
Q
what is the function of glucocorticoids
A
- 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.
5
Q
ACTH
A
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
6
Q
Androgen steroids
A
- function: stimulate protein synthesis (anabolic effects), influence development and growth of male sexual characteristics, and libido in women2. regulation by ACTH which stimulates secretion
7
Q
catecholamines: norepinephrine and epinephrine
A
- 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
8
Q
cushing syndrome (hypercortisolims)
A
- 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
9
Q
CRH
A
corticotropin releasing hormonesecreted by hypothalmusstimulates the synthesis and secretion of ACTH
10
Q
Cushing Syndrome manifestations
A
- 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
11
Q
Adrenocortical insufficiency etiology
A
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)
12
Q
adrenocortical insufficiency manifestations
A
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
13
Q
Secondary Adrenocortical Insufficiency etiology
A
- pituitary or hypothalamic hypofunction
14
Q
secondary adrenocortical insufficiency manifestations
A
- 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
15
Q
hyperaldosteronism
A
- 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
16
Q
hypoaldosteronism
A
- 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)
17
Q
Pheochromocytoma
A
- 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
18
Q
hypothalamus anatomy
A
- 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)
19
Q
pituitary gland anatomy
A
- 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
20
Q
hyperpituitarism of anterior pituitary
A
- 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
21
Q
hypopituitarism of anterior pituitary
A
- 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
22
Q
diabetes insupidus
A
- 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
23
Q
syndrome of inappropriate ADH (SIADH)
A
- 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
24
Q
cellular mechanism of hormone action is dependent on..
A
- 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
25
pancreas islets of langerhans
1. 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
26
insulin structure and regulation
1. 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
27
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
28
insulin mechanism of action in skeletal and adipose tissue
1. 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
29
insulin mechanism of action in liver
1. promotes glucose uptake through GLUT-2 transporter -it is a membrane protein that allows two-way directional glucose movement
30
insulin mechanisms of action to brain
1. insulin is not required for entry of glucose into other tissues including brain-GLUT-1 transporter allows glucose into other tissues including brain
31
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
32
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
33
somatostatin
-produced: by d cells-effect: inhibits both glucagon and insulin secretion as well as its own secretion
34
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
35
type 1 DM
1. 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
36
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
37
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
38
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
39
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
40
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
41
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
42
nephropathy from DM
patho: AGE or sorbital products and activation of protein kinase Cmanifestations: microalbuminemia to macroalbuminuria
43
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
44
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)
45
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
46
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
47
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
48
structure of thyroid gland
contains follicles that contain colloid (contains stored thyroid hormones)parafolliculuar cells are scattered between (C-cells)
49
regulation of thyroid secretions
1. 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)
50
Thyroid hormones
1. 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
51
function of c-cells
secrete calcitoninincreased calcium stimulates release of calcitonin
52
action of calcitonin
inhibits osteoclastic bone reabsorption
53
hyperthyroidism and thyrotoxicosis
1. have elevated t3 and t42. most common is autoimmune d/o Graves' disease, can be adenomas, exogenous thyroid hormone intake, TSH secreting pituitary adenoma3. graves disease: immune responds to microbe proteins that have same amino acid sequence as self proteins, breakdown in helper T tolerance, develops autoantibodies to TSH receptor (thyroid receptor stimulating antibody), this binds to and activates TSH to produce excess amts of t3 and t44. sx: elevated t3 t4, TSH suppressed in primary causes but elevated with pituitary adenoma and hypothalamic disease-high iodine uptake, autoantibody present with graves-increased BMR, heat intolerance, increased appetite, wt loss, -over activation os SNS: increased CO, palpitations, tachy, nervousness, poor concentration, insomnia, weakness, tremors, increased bone reabsorption-in graves: increased number and size of follicles with lymphocytic infiltrates and scanty colloid; exopthalmosis (infiltration of retro-orbital space by leuk, edema, extracellular matrix components)-thyroid storm: if untreated, abrupt tachy, fever, agitation, n/v, diarrhea, restlessness, psychosis
54
hypothyroid
1. deficiency in thyroid hormone2. hashimoto thyroiditis, iodine deficiency, thyroid ablation, familial/genetic, drugs (lithium, amioderone)3. hashimoto: breakdown of helper T cell tolerance, develop autoantibodies agains follicular cell membrane (TSH receptor blocking antibody); it binds to TSH receptor and blocks stimulation of t3 and t4, loss of thyroid cells because CD8 mediated destruction, CD4 production of proinflammatory cytokines, antibody dependent cell mediated cytotoxicity, leukocyte infiltration, follicular atrophy, fibrosis of gland4. low t3 t4, elevated TSH is most sensitive test for early hypo, low TSH for secondary hypo, high antibody titers wit hashimotos, decreased iodine uptake-cretinism in infants/children: impaired skeletal system, short stature, course facial features, severe MR-myxedema older children/adults: hypothermia, decreased BMR, round puffy face, periorbital edema, large tongue, course brittle hair, weakness, slow thinking, depression-goiter: reflects impaired synthesis of hormones; etiology: dietary iodine deficiency, hypothyroidism, ingestion of goitrogens, heridtary enzymatic defects; types: diffuse nontoxic or multinodular
55
neoplasms of thyroid
1. fillicular adenoma (benign; solitary nodule); thyroid carcinoma (solitary nodule, most common, may be multinodular), medullary carcinoma (c-cell neoplasm that cuases increased production of calcitonin)
56
structure of parathyroid
-two small glands by upper and lower poles of thyroid lobe-contain chief cells and oxyphil cells -chief cells secrete parathyroid hormone (PTH)
57
Parathyroid hormone (PTH)
-decreased Ca stimulates synthesis and secretion-increased inhibits-phosphate levels, but unknown how-functions: stimulates Ca release from bone, increases renal reabsorption of Ca, stimulates renal conversion of vit D to active form, augments Ca absorption in gut, increases phosphate excretion in kidneys
58
hyperparathroidism
1. excess secretion of PTH2. adenomas, hyperplasia, neoplasms or cancer3. manifestations: increased calcium and PTH, renal stones, bone fx, GI disturbances, CNS and neuromuscular problems4. secondary hyper: glandular hyperplasia and overproduction of PTH associated with conditions that depress calcium levels; renal failure is most common, vitamin d deficiency
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hypoparathyroidism
1. deficit in PTH2. parathyroid damage in surgery, genetic, autoimmune3. manifestations: hyocalciumia, muscle spasms, cardiac arrhythmias
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osteoporosis-osteoclasts: bone reabsorption-osteoblasts: synthesize bone material
1. increased porosity of the skeleton from reduced bone mass2. risk fx: older, white or asian, small bone structure, fx history, sex hormone deficiency, smoking, low calcium or vit d, sedentary lifestyle,3. trabecular bone is sponge-like in center of long bones and vertebrae, more active, more subject to turnover and remodeling4. cortical bone is hard outer shell,5. peak bone mass achieved during young adulthood, age 30-40 bone loss averages 0.5% to 0.7% per year6. patho: resulting form imbalance of decreased formation and increased reabsorption, osteoblast and osteoclast acivity, osteoblas regulation of osteoclast activation-usually in bones with abundant trabecular bone (wrist, hip, spine high risk, rely on trabecular bone for strength)-estrogen deficiency and decreased testosterone increases osteoclast activity becasue they have estrogen receptors that slow activity; also estrogen deficiency causes release of pro-inflammatory cytokines that increases osteoclast differentiation and activity -age decreases osteoblast replication and activity or response to bone reabsorption; slower manufacture of vit d in skin, decreased renal mass w/ aging results in decreased amounts of activated vit d; capacity of intestion to absorb calcium declines w/ age-mechanical forces stimulate normal bone remodeling so reducing activity increases rate of bone loss, bone reabsorption exceeds bone deposition -glucocorticoids attenuate osteoblast differentiation7. osteopenia 1-2.5 below peak density and osteoporosis greater than 2.5 below8. results in fx; kyphosis (small fx in vertebrae and they heal causing forward curvature of spine)
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Neuron structure and function
-cell body is soma, contain dendrites that recieve info and pass messages to other dendrites-axons are branches extensively at their end -unmyelinated neurons pass AP along axon and myelinated by saltatory conduction-AP generated by sum of all graded membrane potentials on dendrite or cell body
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action potential types
stimulatory: allows influx of Na and Cainhibitory: allows influx of Cl
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synaptic integration
-if sum of all graded membrane potentials including inhibitory or stimulatory is sufficient to raise the potential to threshold, an action potential is initiated (synaptic integration)
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nerve terminal
when the impulse reaches the axon terminal, depolarization opens voltage gated Ca channels that allows Ca influx and trickers docking of synaptic vesicles containing the neurotransmitters and neurotransmitter release
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axon transport
flow of substances inside the neuron from the soma to the synaptic ending and can also be retrograde
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excitatory neurotransmitters
acetylcholineglutamate: one of most abundant in brain; breakdown in terminating normal excitatory signals lead to sustained elevations in intracellular Ca that cause cell apoptosis and degeneration
67
inhibitory transmitters
GABA the most commonneuropeptides: substance P, endorphinsmonoamines: norepinephrine, seratonin, dopamine, histamine
68
support cells of CNS
a. schwann cells: wrap around axons to form myelin sheath, gaps in myelination called nodes of Ranvier; insulates/protects axons from extracellular environment; provide support to unmyelinated axons
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types of neurons
1. lower motor neurons/somatic: from spinal cord to skeletal muscle-alpha motor neurons: innervate muscle fibers, nerve to muscle ratio vaires-gamma motor neurons: innervate spindles2. neuromuscular junction: terminal portion of the motor nerve, the synaptic clefet and end plate region of muscle-no inhibitory synapses exist on skeletal muscle fibers
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types of receptors
cholinergic-nicotonic: skeletal muscles and post-ganglionic-muscarinic: cardiac, smooth muscles and glandsadrenergic-alpha adrenergic and beta adrenergic receptors
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normal skeletal muscle
1. two types of muscle fibers distributed alternately across muslce-slow twitch fibers "red muscle": more dependent on fat catabolism, tonic contractions like wt bearing-fast twitch fibers "white muscle": higher dependence on glycogen, rapid phase contractions like sudden movement-motor neuron determines fiber type2. have muscle spindles: respond to muscle stretch and maintain muscle tone
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neuronal injury in PNS
segmental demyelination: 1. disintegrating myelin engulfed by schwann cell and macrophages-schwann cell injury: cell is repaired/replaced2. inferior myelin replacement: further axonal injuryaxonal degeneration1. destruction of axon with secondary disintegration of the myelin sheath-wallerian degeneration: degeneration of axon distal to axonal injury; new terminal sprouts from proximal segment; uses schwann cell sheath pathway if it can-injury above the hilium results in axon death and cannot be replaceddenervation denervation atrophy1. decreases in mucle cell content, muscle cell atrophy and weakness2. receptors in devervated fibers spread across the muscle membrane -spontaneous discharge (fasciculations)-spontaneous contractions (fibrillations)reinnervation1. neighboring axons extend sprouts to reinnervate the denervated myocytes-may lose some fine motor movement abilities-assume the muscle fiber type of the innervating neuron
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neuronal injury of cranial nerves-axonal injury
1. wallerian degernation followed by sprouting 2. proprer guidance for the sprouts is generally lacking3. neuronal loss and cannot be replaced
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neuropathies
1. sensory or motor-mononeuropathy: sensory sx and deficiets associated with a single peripheral nerve-polyneuropathy: sensory sx and deficits associated with multiple peripheral nerves; symmetric sensory loss affects legs more than arms-radiculopathy: sensory sx along dermatome, associated with diseases of spinal nerves/nerve rootDM Neuropathy: 1. weakness, loss of reflexes usually ankle resulting in gait changes, foot deformaties like hammertoes and collapse of mid foot; blisters and sores from numb areas becasue pressure or injury goes unnoticed2. autonomic dysfunction: decreased perspiration or sweating Shingles (Herpes Zoster): infectious neuropathy1. reactivation of latent chicken pox virus in sensory nerve ganglia of spinal cord secondary to decreased immunity2. patho: inflammatory response to virus->neuronal injury and loss3. vesicular skin eruption in distribution of sensory dermatomes, radicular pain, burning/tingling, risk for post-herpatic neurologiaGuillian Barre- acute inflammatory neuropathy1. thought to be an immunologic reaction directed at spinal nerve root and peripheral nerve myelination2. viral influenza like illness, CMV, epstein-barr etc3. patho: t-cell mediated autoimmune against myelin: infiltration by lymph and macs, segmental demyelination by macs, decreased nerve conduction velocity or complete loss of nerve conduction,and inflammatory response/cytokine release may damage axons 4. ascending paralysis begins as weakness of distal limbs; parethesias and pain; possible autonomic instability; elevation of cerbral spinal fluid protein levels; prolonged recovery
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etiology of autoimmunity is either
1. genetic2. infection: up regulates the number of co-stimulators on surface of T cells and causes change in tissue ("self" protein or virus adds protein to tissue), molecular mimicry (immune response to microbe proteins that have same amino acid sequence as self)3. injury from inflammation or other that alters the display of self
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botulism (clostridium botulinum)
1. toxins bind to peripheral nerve endings and block synaptic release of acetylcholine2. weakness, blurred vision, diplopia, dysphagia, paralysis of resp and skeletal muscle
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myasthenia gravis
1. autoimmune d/o of neuromuscular transmission usually in females more than males2. genetic/familial, thymic abnormalities3. patho: antibodies (IgG) against post synaptic nicotinic ACh receptors in muscle lead to loss of functional AChR-bind to receptor on motor end plate and block ACh binding and receptor activation, it is immune mediated destruction of the receptor -decreased muscle contraction caused by decremental response with repeated stimulation and muscles with small motor units are most often effected (ocular)4. sx: weakness (first noted in eyes), ptosis/diplopia, fluctuating weakness and fatigability, improvement in sx after a period of rest and after administration of acetyl-cholinesterase inhibitors or acetylcholine; dx based on response to tensilon, presence of antibodies, and repetitive single fiber EMG-loss of post synaptic receptors at motor end plate, circulating antibodies to AChR (IgG), and scattered lymphocytes around motor end platestreatment with cholinesterase inhibitors
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postpolio syndrome
1. from previous viral poliovirus infection2. patho: neuronal fatigue, new neuronal loss, origianl disease causes nerve cell death, years of high use of these enlarged motor units adds stress to neuronal cell body which may not be able to maintain the metabolic demands over time resulting in slow deterioration of motor units, eventually nerve terminals malfunction and permanent weakness occurs3. sx: weakness in musles previously effected by polio, muscle atrophy, pain and fatigue, appearance of sx may also be related to age associated changes that finally reveal deficit
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Muscle Dystrophy
1. duchenne muscular dystrophy (DMD) most common and most severe -familial, x-linked-patho: genetic defect stops formation of dystrophin which anchors the sarcomere to the sarcolemma cell membrane in myocytes; poorly anchored sarcomeres tear themselves apart during contraction (actin and myocin cross linking); regenerated defective muscle fibers perpetuate the process-sx: begin at age 2-3, usually in w/c by 7-12, only 25% live to 21; muscle weakness, atrophy, contractures, heart failure; lab (elevated CK, western blot shows absence of dystrophin); histology (degernation, necrosis, phagocytosis of fibers and fat and connective tissue replace muscle fibers), associated w/ cognitive impairment2. becker muscular dystrophy (BMD) less severe than DMD-genetic x-linked-patho: defect diminishes the amount of dystrophin and molecular wt allowing anchorage of muscle to cell membrane but genetic alterations impair long term function -sx: later in childhood or adolescence, progesses slowly w/ longer life expectancy; PROXIMAL muscle weakness, cardiac muscle disease; western blot shows altered dystrophin size
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myotonic dystrophy (sustained involuntary contraction of a group of muscles with delayed relaxation)
1. genetic-autosomal dominant disease2. patho: defect causes nucleotide (CTG) repeats on the gene, with each succeeding generation, the number of repeats increases and sx appear at a younger age; genetic defect influences the level of protein in muscle which alters msucle fiber stucture and function3. sx: involuntary contraction of a group of muscles-delayed relaxation after msucle contraction; weakness of DISTAL extensor muscles-hand feet; atrophy of muscles of face, ptosis, cataracts; histology (variation in fiber size, degernation, necrosis, phagocytosis of muscle fibers) ONLY DYSTROPHY TO SHOW PATHOLOGICAL CHANGES IN MUSCLE SPINDLE AS WELL
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toxic myopathies
1. thyrotoxic myopathy: acute or chronic PROXIMAL muscle weakness that sometimes occurs from hyper or hypothyroid disease; protein catabolism and altered metabolism, therefore altered msucle function; histology (myofiber necrosis, increased number of nuclei, regeneration and interstitial lymphocytosis)2. ethanol myopathy: from heavy or binge drinking->produces breakdown of muscle tissue (rhabdomyolysis)->disintegration of striated muscle fibers with accompanying myoglobinuria; sudden onset of muscle pain, swelling and proximal muscle weakness; histology (swelling of myocytes, necoriss, phagocytosis of muscle cells and nerve denervation)3. steroid myopathy: from cushing syndrome or therapeutic administration of steriods: related to decreased protein synthesis, increased protein degradation, alteration in carb metabolism and/or decreased sarcolemma excitability (remember corticosteriods are catabolic); will have proximal muscle weakness and atrophy
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spinal cord anatomy
-thirty one pairs of spinal nerves, and contain both motor aand sensory neurons-supplies and recieves information specific to body distribution called dermatome-reflex are impulses which directly stimulate the motor neuron within the spinal segment
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upper motor neurons anatomy
-cerebellar -pyramidal -extrapyramidal -somatosensory system
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somatosensory System
-pathways for sensations of position and vibration and fine touch-pass directly through dorsal column-pathway for sensations of pain and temperature pass through dorsal column and lateral spinothalamic tract of cord-pathway for sensations of crude touch and pressure pass through dorsal horn and ascend in anterior spinothalamic tract-at thalamic level the quality of sensation is perceived but fine distinctions not made, fine distinctions made in cortex (homunculus)
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cell bodies originate in different parts of the brain and synapse at the basal ganglia; neurons from basal descend downt he brain and spinal tract and regulates voluntary and involuntary gross body movements and maintains posture
extrapyramidal upper motor neurons
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Pyramidal upper motor neurons
-corticospinal tract: the cell bodies originate in the cerebral cortex and descend down the brain and cord without synapsing in the basal ganglia; synapse with alpha motor neurons and responsible for voluntary fine motor movement-corticobulbar: cell bodies originate in crebral cortex and descend to the brainstem where thy synapse with motor nuclei of the cranial nerves; responsible for fine motor movement and control the face and tongue
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physiology of pain
1. nociception: how it becomes concious-transduction, transmission, perception of pain, modulation2. transduction: receptors (bare sensory nerve endings) respond to noxious, mechanical, thermal and inflammatory mediators to elicit action potential; (bradykinin, prostaglandins, substance P, serotonin)3. transmission: pain impulse travels from A and C peripheral fibers to dorsal horn (a delta nerve fibers myelinated=fast) (c unmyelinated=slow); cross to otherside in spinal cord, ascend through lateral spinothalamic and spinoreticular tracts to reticular formaiton and thalamus; synapse with third in cortex4. perception of pain occurs in brain by reticular system that sends info to limibic system and integrates autonomic response; thalamus localizes p[ain, somatosensory cortex characterizes and interprets pain and limibic systme is emotional and behavioral response 5. modulation of pain: pathways to inhibit is by the one from cortex descending to thalamus and periaqueductal gray matter (PAG located in mid brain and sends signals to midline raphe nucleus in medulla which sends signals down cord and synapse in dorsal horn to inhibit release of excitatory neurotransmitters of pain)6. dorsal horn is the gate keeper in which ist recieves inhibitory signals from raphe nucleus and pain can also be modulated by stimulation of larger sensory afferents from skin that block the impulse and therfore block pain
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patho of pain
1. abnormal fx of processing -peripheral: sensitization of nociceptors enhance response to noxious stimulation and newly acquired responsiveness to a wide range of stimuli; damaged or diseased nerves can produce abnormal painful sensations (dysesthesia); growth of axonal sprouts, formation of ectopic foci which fire spontaeously, or upregulation of receptors-central (at dorsal horn) can be from sensitization of second order neurons triggered by less timuli or augemented strength of stimulation (also called summation/wind up) and prolonged discharge or from spontaneious impulse acitivity or activation of additional neurons to conduct pain impulse or loss of inhbitory interneuron activity-central (brain) sensitization of third order neurons or reorgantizaiton of neural connections or altered perception of pain2. nociception is sustained in chronic bain: sponstaneous self-sustaining neuronal activity or also may be from secondary to neural inflammation, chronic nerve compression, lesions, and down-regulation, or loss of modulation pathways
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spinal cord trauma
1. occurs form hyperextension, hyperflexion, vertical compression or rotation of spine2. patho: central gray matter microscopic hemorrhages, white matter axonal edema->impairs microcirculation; decreased perfusion ->ischemia->disruption of myelin and degeneration of axons; maximal at injury site and two cord segments above or below it-inflammatory response causes further ischemia and vascular damage,-necorsis, and scar tissue formation3. sx: spinal shock (normal acitivyt of spinal cord ceases at and below level of injury; complete loss of reflex function); paraplegia, quadraplegtia, autonomic dysreflexia (hyperactivation of SNS in response to noxious stimulation of sensory receptors belwo the level of cord lesion
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herniated intervertebral disk
1. weakness and degeneration of the annulus fibrosus and posterior longitudinal ligament can cause bulging or protrusion of nucleus pulposus into spinal canal-usually herniations occur posterolaterally->compromises spinal nerve root producing pain; irritation/inflammation of the dural membranes also may be responsible for apin-occurs commonly at L4-5 and L5-S12.sx: pain radiating along dermatome, loss of sensation (temperature, pain, touch) as the lateral spinothalamic fibers are most lateral; at risk for possible motor weakness from compression ofthe lateral corticospinal tract
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brown sequard syndrome
1. occurs with trauma or lesions that involve one-half of cord typically occurs in cervical region-loss of proprioception on same side of lesion, loss of pain and temp sensation on opposite side of body, loss of voluntary motor function from corticospinal tract on same side as lesion
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syringomyelia (central cord syndrome)
-cyst, tumor or trauma which injures the central gray matter of the cord, loss of motor power and sensation at the level of the lesion, for cervical cord lesions it is across the shoulders and upper arms
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structure of CNS
1. braina. cerebrum (cerebral hemispheres and cortex-lobes, and limbic system (border around the diencephalon, hippocampus, amygdala; involved in emotional experiences and survival behavior)b. basal ganglia -subcortical (lie lateral to the thalamus)-includes caudate nucleus, putamen, globus palladius, substantia nigra, subthalamic nucleas(copus striatum consists of caudate nucleus, putamen and globus palladius)-important in cognition and emotionc. crebellum (anterior, posterior and flocculonodular lobes)d. diencephalon (structures surrounding the 3rd ventricle and forming inner core of cerebrum (thalamus, hypothalamus, subthalamus, pituitary/pineal body)e. brainstem (midbrain, pons, medulla) -reticular formation (collection of nerve cell bodies called nuclei within brain stem that regulate vital reflexes and maintain wakefulness, awareness and alertness; projects to the thalamus)
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what are the protective structures of the CNS?
1. cranium2. meninges-dura mater, arachnoid membrane, subarachnoid space, pia matter3. crebrospinal fluid and ventricular system-primarily produced by ependymal cells in the choroid plexuses-CSF is reabsorbed into the venous circulation through arachnoid villi
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what regulates the CNS blood supply?
CO2 regulates blood flow within the CNS
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blood brain barrier anatomy
1. tight junctions between the capillary and endothelial cells 2. encircling astocyte feet3. the entry of substances from the blood into the CNS is controlled by ependymal cells in the choroid plexuses
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what are neuroglia?
support cells of CNS1. astrocytes-provide nutritional support-help regulate flow to provide oxygen to neurons in need-provide structural support to neurons-help maintain blood brain barrier-participate in response to CNS injury (release cytokines, multiply in number during injury, involved in tissue repair and scar tissue formation)-regulate extracellular concentrations of neuotransmitters (help terminate neuronal responses to glutamate)2. oligodendrocytes -wrap around axons to form myelin sheath3. microglia-phaocytic cells of brain-act as brain immune cells
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what does ICP measure
intracranial pressure = CSF volume + blood volume + brain tissue volume -normal is equal to the pressure exerted by the volume of cerebral spinal fluid + pressure exerted by volume of blood + pressure exerted by volume of brain tissue-normal is less than or equal to 15mmHg
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what is CPP
cerebral perfusion pressure is the pressure required to perfuse cells of brain -CPP=MAP-ICP
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increased intracranial pressure
1. edema (tissue volume), tumor (tissue volume), hydrocephalus (accumulation of CSF within ventricular system), HTN, hemorrhage, vasodilation2. sx: retinal edema, decreased perfusion/collapse of capillaries->ischemia->cell death; tissue atrophy from compression and lack of circulation; reflex increase in BP to maintain perfusion; change in LOC from ischemia, altered neuronal conduction, compression of cortical structure or compression of ascending reticular activating system; herniation
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what are the types of herniation of brain
1. cingulate 2. central transtentorial 3. uncal (lateral)4. cerebellar tonsillar herniation into foreman magnum
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head trauma
1. open or closed2. results in: skull fx, alteration of consciousness, localized to diffuse neuronal cell injury and death and loss of function, edema->^ICP->compression of surrounding tissue and vessels, scarring->seizure focus, hemorrhage and hematoma, infection
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vascular trauma of CNS
1. epidural hematoma-collection of arterial blood between the dura mater and cranium and expands rapidly2. subdural hematoma-collection of blood between the dura and arachnoid and usually slower and usually venous3. subarachnoid hemorrhage/intraparenchymal hematomas-blood escapes into subarachnoid space->irritation of meninges, disruption of CSF circulation/absorption->rapid rise ICP-intraparenchymal hemorrhage causes tissue compression
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CV d/o
1. TIA (brief and reversible impairement of neurological fx due to interruption of blood flow) sx: last seconds to hours and neuronal cell death frrom ischemia or hypoxia is 5-10 min for cortical neurons and 30min for brain stem neurons; increased risk for reoccurance2. Stroke (sudden onset of focal neurologic deficit that persists for at least 24 hours due to abnormality of cerebral circulation)-types: a. thrombotic usually in larger arteries and common in internal carotid, middle cerebral artery, posterior cerebral artery and basilar artery; most commonly from atherosclerosis and variable by collateral flowb. lacunar is microinfarcts that involve small arteries assoicated with HTN, DM, and atherosclerosis, and can be silent or produce significant motor and sensory deficitsc. embolic involves larger and small arteries; traveling from heart, aorta, carotids->occlude middle crebral artery since it carries majority of blood flow to hemispheres; if traveling from vertebral and basilar arteries->occlude basilar artery, or posterior cerebral artery2. patho: initiates ischemia by neurons effected, after that surrounding neurons die from excess stimulation of glutamate receptors called neuronal excitotoxicity -ischemia depletes energy supply to brain, inhibits NaKATPase->loss of normal transmembrane ion gradient which leads to increased intracellular Na and increased extra K; increased intra Na reduces Na dependent glutamate uptake-increased K depolarizes nerve terminals causeing release of glutamate from nerve terminals and increased levels of extracellular glutamate causes excessive stimulation of its receptors -increased in Ca influx stimulates sustained acitvation of enzymes that cause protein breakdown, free radical formation, lipid peroxidation, fragmentation of DNA and nuclear breakdown in neuron -directly stimulates NO production in neurons -sustained activation = cell dath and glutamate receptor antagonists are given to reduce size of ischemic lesions -neurons shrink, diappearance of nucleolus, injured axons undergo swelling, axonal transport may be dirupted (wallerian degenration followed by spouting; proper guidance for spouts lacking) loss not replaced -inflammatory response->vasodilation->^ICP3. sx: depends on location; modified by collateral blood flow
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hemorrhagic CVA
1. HTN, rupture of aneurysm or malformation, platelet or coagulation d/o, cocaine and amphetamines (causes rapid increase BP or drug induced vasculitis)2. patho: hemorrhage, inflammation, edema,increases ICP; secondary vasospasms from blood toxicity->ischemia; compression ischemia/neuronal cell death3. sx: severe HA and/or sudden decrease in consciousness, seizures, focal deficit, increased risk for bleeding/rebleeding
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what regulates wakefulness and cognition
arousal or state of wakefulness is dependent on reticular activating system cognition is mediated by functional cerebral cortex
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disorders of arousal and cognition
1. etiologya. destructive mechanisms by lesions in RAS, hemorrhages, ishemic infarts, abscesses, tumors, deposition of neuitic plaques/neurofibrillary tangels, amyloid, b. compressive mechanisms c. metabolic-toxic mechanisms by substrate depletion, hypoxia, toxins, fluid and electrolyte imbalanced. psychogenic arousal alterations2. sx: confusional states, midbrain lesions result in failure of arousal or coma, lesions of thalamus are associated with d/o of consciousness, lesions above the midbrain must be bilateral to cause coma, and decorticate rigidity or decerebrate rigidity
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seizures/epilepsy
1. seizure: an intermitten distrubance in cerebral fx caused by abnormal synchronous discharge of cortical neurons epilepsy: recurrent seizures2. moslty in children, generally outgrow as adults3. idiopathic, genetic, secondary to brain injury, lesions, dieseases4. patho: epileptogenic focus and synchronous neuronal activation -epileptogenic focus: an abnormally excitable neurons (a population of pathologically excitable neurons perhaps have a lower threshold for depolarization, increased permeability or chronically may be in a state of partial depolarization) or more glutamate or px with inhibitory system-spread by extracellK accumulation around epileptogenic focus that causes depolarization and by increases in frequency of discharge in epileptogenic focus that enhances Ca influx into nerve terminal swhich increases neurotransmitter release at excitatory synapses -synchronous discharge/seizure is characterized by sudden brief attacks of altered consciousness, motor activity or sensory phenomena5. grand mal seizures: in clonic phase the inhibiting neurons in other parts of hte brain inhibit cortical excitation to cause the interruption in the seizure discharge and eventual control 6. anticonvulsant target (categories for inhibition of Na and or Ca channels, enhance GABA receptor function and increase GABA levels)
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Multiple Sclerosis
-autoimmune destruction of myelin episodic of neurologic deficits, attributable to diffuse demyelinating white matter lesions-usually female-patho: CD4t cell autoreactivity to a single myelin basic protein (MBP)->one of the proteins in the membrane of myelin sheathTh1 secretion of cytokines and inflammatory response; macrophages CD8t and B cell activation against MBP; demyelinated patches called plaques-axons usually preserved-remyelnation with thinned myelin sheath which is inferior to the orginal; repeated exacerbations of autoimmune activity and oligodendrocyte injurygliosis (glial scarring)-permanent plaques result in sharply defined areas of gray discoloration of white matter and permanent disruption of conduction-sx: neurological deficit followed by gradual, partial remission and with progression less improvement between exacerbations and increased neurological disfunction; -sensory px with optic nerve, spinal cord and brain stem (paresthesis, numbenss, decreased proprioception, thermal sense, pain); -motor plaque in brain stem (ataxia, nystagmus, pararlysis, hyperreflexia, decreased coordination) plaque in spinal cord (motor impairment of trunk and limbs-autonomic: bladder incontinence, impotence
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Alzheimer's disease (degenerative d/o of cerebral cortex) Patho
proposed patho: collection of neuritic process around a central amyloid AB peptide core=neuritic plaques->interfere with synaptic transmission of acetylcholine, tend to occur in the hippocampus, amygdala, and cortex-the major protein in plaques is amyloid beta peptide productions: formed from abnormal breakdown of amyloid precursor protein (APP); normally APP is made by neuronal membrane and expressed in cell surface, and cells use it to support the growth of neurites, and when broken down the products usually produce the AB peptide and that produced is usually cleared by brain -in AD more AB peptide is produced than can be excreted so they aggregate becoming neurotoxic causing loss of neurons and triggers the release of glutamate from glial cells-neurofibrillary tangles are from microtubular proteins in the neuron that become distorted and twisted; this displace or encircles the nucleus causesing interferrance with neuronal function and causes neuronal loss; they are insoluable and perisst in the nervous tissue after death of cells-loss of neurons and interffance with normal transmission -inflammatory repsonse occurs becasue the AB deposits; causes oxidative damage and alterations in calcium homeostasis
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Alzheimer's disease (degenerative d/o of cerebral cortex) etiology
1. usually after age 50 and increases with age; more female than male2. chromosome 21 increases the metabolism of APP to AB and increases production of AB3. mutations in APP and preinsilin 1 and 2 will increase production of AB4. e4 isoform of apolipoprotein E (apoE4) (50% of AD pt over age of 60 have it and it may facilitate in neuronic plaque formation of decrease AB clearance)5. SORL1 protein deficiency causes APP to accumulate in cell where it is disregarded into AB fragments
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AD manifestations
1. progressive dementia from progressive neuronal loss and reduciton in brain acetylcholine and other neurotransmitters2. early: impairment of higher intellectual fx and alteration in mood and behavior3. progressive: disorientation, memory loss, aphasia, fx decline4. profoundly disabled mute, immobile
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histology of AD
presence of plaques and neurofibrillary triangles and brain tissue atrophy
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Parkinson's (degenerative d/o of basal ganlia and brain stem)
1. idiopathic most commonly, gene mutations, exposure to certain toxins/heavy metal poisoning; drugs, secondary from trauma or other diseases 2. patho: loss of dopaminergic neurons in substantia nigra and nigrostriatial pathway decreases dopamine and causes loss of normal dopamine and acetylcholine balace in striatum-results in increased inhibitory output from striatum3. histology: pale substantia nigra; Lewy bodies (neuronal filaments around a protein core); increased striatal inhibitory output is manifested as diminished facial expression, akinesia/bradykinesia, rigidity, pill rolling, postural instability, loss of spead of normal postural reflexes, depression, slowness of thinking4. treatment: decrease ACh (acetylcholinestergics); l-dopa is the precursor to dopamine and will work until dopamine receptors down regulate; deep brain stimulation; placement of lesions in extrapyramidal system
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Huntington's
-hereditary characterized by progressive movement d/o, dementia, and neuronal degeneration in the corpus striatum and frontal cerebral cortex1. genetic autosomal dominant mutation to chromosome 4; encodes protein huntingtin; this increases number of CAG repeats and this increae is inversely r/t age of onset (increasing repeats/length leads to progressively earlier disease presentation)2. patho: mutant protein damages brain neurons but insufficient supply of energy for cell fx, interfers with manufacture and packaging of transmitters and antioxidants->ROS damage-mutant protein is degraded and forms aggregates that interfere with normal neuron fx, fials to fold properly and accumulates and causes apoptosis; ultimately loss of neurons of corpus striatum (caudate nucleus and putamen) atrophy -decreased striatal inhibitory output and modulation of movement -sx: involuntary rapid jerky movements (chorea), slow writhering movments of limbs and trunk (athetosis); cognitive impairment/dementia, depression; -tx of sx: dopamine antagonists reduce involuntary movement; block inhibition of remaining striatal neurons
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amyotrophic lateral sclerosis (ALS) (degenerative d/o of upper and lower motor neurons)
-progressive neuromuscular d/o caused by degernation of upper and lower neurons1. familial/herditary (SOD1 superoxide dimutase; TAR DNA binding protein; FUS fused in sarcoma/TLS translocated in liposarcoma; ubiquilin 2 gene-viral and autoimmune or other environmental fx2. patho not well known: SOD1 defect intereferes with enzy e that produce SOD1 (antioxidant)=free radical damage to upper and lower motor neurons and degernation and loss-ubiquilin 2 recycles damaged or misfolded protein in mortor and cortical neurons so mutation with this will cause px with disposal -glutamate toxicity may also contribute to neuronal loss -results in degernation and loss of lower motor neurons and skeltal muscle denervation and skeletal muscle atrophy3. sx: muscle weakness, atrophy, eventual complete loss of use (1sts sx are asymmetric weakness hands and diff completing fine motor tasks); hyperreflexia/spasticity arms/legs b/c degeneration of corticospinal tract neurons->release of reflexes from inhibition; cramping and fasciculations; involvment in bulbar muscle=speech, swallowing, breathing, coughing; presevation of intellect; fatal within 3-5 years from involving resp
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bacterial meningitis
-infection of arachnoid and pia membranes, CSF within subarachnoid space with inflammatory response1. neonate-strep B, E. coli; children/adults-H influenza, neisseria, strept pneumonia2. patho: entry into CNS thorugh choroid plexus or altered areas; multiply and host defenses are inadquate to control; inflammation and cytokine release (TNFa, IL1 and others); increased permeability of blood brain barrier=edema; vasodilation and rupture of small vessles and bleeding; stimualting of clotting causes thrombosis; neut migration into subarachnoid->thick exudate->interferes w/ normal CSF drainage->hydrocephalus; scar tissue formation and neuron loss3. sx: increased ICP and meninges irritation=HA, photophobia, nuchal rigidity, altered mentation, irritable, fever; CSF cloudy, WBC, increased protein concentration, decreased sugar content; petechial rash; -complications: septicemia, secondary infection in brain can result in abscess, herniation
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viral meningitis
1. herpes, mumps2. patho: self limiting inflammation3. sx: less fulminant than bacterial meningitis; meningeal irritation, fever, HA, n/v, alterations in LOC, CSF increased lymphocytic, protein increased only as moderate and glucose usually normal; 4. treat sx; rarely fatal in ppl with normal immune
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Lyme disease
-spirochete (borrelia bugdorferi) transmitted from rodents to ppl by tiny hard deer ticksstage 1: acute illness; tick bite, spirochete multiplication in dermis, bull's eye rash, malaise, lympadenopathystage 2: dissemination of spirochetes, migratory muscle and jt pain, cardiac dysrhythmias, SOB, HA, meningeal irritation, cranial nerve involvementstage 3: late chronic; arthritis, infection of brain->encephalitis; neuronal degeneration-> neuropathies-t cell/B cell response: spirochetes capaple of antigenic variation
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d/o visual system
1. lesions-prechiasmal lesions: partial lesion of optic nerve->hemianopia (impaired vision in ipsilateral eye (same side)-retrochiasmal lesions (behind chiasm): cause loss in contralateral field of both eyes; homonymous hemianopia2. glaucoma; -openangle: px with trabecular mesh work or blockage that slows drainage of aqueous humor (controls the flow into canal of schlemm)-angle-closure: narrow angle formed by cornea and iris block drainage (as we age, lens grows bigger, causing narrowing angle)sx: ^IOP, changes in visual field/optic nerve damage3. retinal d/o-detachment: seperation of retina from retinal pigment epithelium; seperation of vitreous from retina; or both -deprives the outer retina of oxygen and nutrients; vision loss4. macular degeneration: loss of central vision most common cause of reduced vision and leading cause of blindness +75 y/o-risk fx: HTN, cigarette smoking, DM, genetic-dry type: waste products from photoreceptors accumulate underneath retinal pigment epithelium and atrophy and degernation of rod and cone and retinal pigment epithelium-wet form: subretinal neovascularization, bleeding, scar tissue formation
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auditory d/o
1. tinnitus: caused by ASA, cerumen, nicotine/caffiene; persistent can be associated with hearing loss and lesions in cochlea or CN82. hearing loss: conductive (external or middle ear px); sensorineuroal (d/t illness of chochlea or CN8); central (d/t disease of cochlear nuclei or auditory pathways in CNS)3. vestibular system: vertigo (simicircular canal=rotational vertigo; utricle or saccule sesations of tilting or listing; lesions of CNS), menier's disease (patho: fluctuating endolymph pressure of inner ear, dilation of membranous labyrnth from increaed pressure[blockage or decreased absorption of endolymph fluid]; sx: episodic attacks can last 2-4 hrs, vertigo, tinnitis, hearing loss episodic which can become permenant form hair cell death)
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migraine HA
-more female than male1. familial or decreased threshold of response to external stimuli (triggers: chocolate, cheese, oranges, tomatoes, MSG, alcohol) (hormone levels)2. patho: trigger phase; aura with slowly expanding area of reduced cortical electrical activity and decrease in blood flow; activation of area in brain stem responsible for physiological response to stress and panic (locus ceruleus) and excitation of trigeminal nuclei; release proinflammatory peptides in meninges and vessles, platelet release of 5HT, and degranulation of mast cell->"neurogenic inflammation" (vasodilation, plasma protein extravasation, swelling of meninges and dura; distrubances in blood brain barrier cause n/v)3. sx: preceded by aura a lot; pain from activation of trigeminal nerve anteriorly and upper cervical nerves C2 and C3 posteriorly; n/v, photophobia, irritability, malaise; nasal congestion, rhinorrhea and lacrimation
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depression patho
patho: 1. monoamine hypothesis: deficit in brain norepinephrine, dopamine, or serotonin: have found decrease in synaptic cleft d/t decrease in presynaptic release or decreased postsynaptic sensitivity; decrease in seratonin receptor binding in serotonin system (the raphe-seratonin normally modulates homeostasis, emotionality, and tolerance to adverse experiences2. classic stress pathway hypothesis: disturbances in fx of HPA axis; impaired feedback inhibition of CRH by endogenous glucocorticoids; hypersecretion of CRH in depressed pts; elevated cortisol levels in persons w/ depression throughout morning and evening; cortisol levels spke erratically over the 24 hour day; decreased glucocorticoid fx in CNS possibly from down regulation of receptors -> decreased glucose metabolism and prolonged elevations in CRH secretion may down regulate CRH receptors in pitutiary and prolonged elevations in CRH may alter DNA expression thus change fx capacity of neurons-antidepressants may upregulate glucocorticoid receptor fx3. other possibilities: decreased frontal lobe volumes and temporal lobe volumes; decreased blood flow to frontal lobe, increased blood flow and oxygen consumption to cortical areas interconnected with amygdala
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postpartum depression patho
unknown relationship between changes in hormones
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schizophrenia patho
1. genetic susceptability interacting with environmental fx->abnormalities in neurodevelopment2. structural abnormalities: enlarged lateral and 3rd ventricles and smaller thalamus, hippocampus, and temporal cortex and amgydala3. biochemical abnormalities: reduced metabolic activity in frontal cortex4. dopaminergic transmission abnormalities: excessive dopamin in limbic areas->positive symptoms-decreased dopamine in prefrontal cortex->negative and cognitive symptoms -positive sx/adding to personality (conceptual disorganization, delusions/hallucinations)-negative sx/underfunctioning (loss of fx, decreased emotional expression, impaired concentreation, and decreased social engagement)
