Endocrine

68 How is cholelithiasis risk incrased in pregnancy and OCP use?

Common in fat, forty, female, fertile Esotrgen increases cholesterol synthesis by upregularting hepatic HMG-coA reducaatse -> bile becomes supersat with cholesterol Progresterone reduces bile acid secreteion and slows gallbaldder emptying -> hypomotile -> cholesteorl precipiates into insoluble crystals that form to make gallstones

769 What ar ethe histo changes in Hashimoto thyroiditis?

** Intense mononuclear infiltrate of lymphocytes and plasma cells with germinal centers. Residual follicles surrounded by Hurthle cells - large oxyphilic cells wit granular cytoplasm that represent follicular epithelial cells that have undergone metaplastic change in response to inflammation

985 20 year old woman comes to ED with lethargy, abdominal pain and nausea. She has had polyuria and excessive thirst for one day. Also compains of dysuria and chills over the last few days, but did not seek medical care until today. PE shows tachycardia and dry mucous membranes. BMP shows: low sodium and chloride, low bicarb, increased BUN and Cr, normal calcium and 698 glucose. What is the resepctive extracellular and increased potassium concentration pattern?

**Increased extracellular, decreased intracellular Pt is in DKA - precip. by infections, usually UTI - loss of K+ in urine via glycosuria induced osmotic diuresis and hypovoluemia mediated increase in aldo secretion -> total body K+ deficit reflected by decreased intracellular K+ stores - 98% of body potassium is stored intracellularly - despite low intracellular potassium levels, EC potassium concentrations are normal or increased due to: 1. loss of intracellular free water by increased plasma osmolarity -> EC movement of k+ secondary to increasing k+ concentration 2. lack of insulin causes EC shifting of potassium as insulin promtotes cellular uptake of K+ Careful when giving insulin and IV fluids bc interventions force potassium back into cells -> drop in serum potassium due to total body deficit - despite normal or elevated serum potassium -> admin of potassium supplement is essential when treating patient in DKA

15239 Diabetic nephropathy progression

1. hyperfiltration 2. increase in intraglomerular capillary pressure -> glomerular structural change - BM thickening, mesangial expansion, broadening of podocyte foot processes -> loss of small amounts of albumin in the urine - albuminuria is early sign of nephropathy 3. later - widespread glomerulosclerosis (Kimmelstein - Wilson nodues) -> decrease in GFR

770 Functions of thyroid peroxidase

1. ox of I- to I2 2. iodination of thyroglobulin 3. coupling reaction between 2 iodized tyrosine residues to produce T4

1 week old boy is brought to ED with poor feeding, lethargy and unusual muscle movements involving left thumb and hand over last 2 days. Unusual flexion of left wrist and thumb and extension of fingers are observed with cuff BP measurement. PE reveals hypplastic mandible, low set ears, bifid uvula, cleft palate. CXR reveals decreased soft tissue attentuation in R anterior mediastinum. Findings suggest imapreid development of?

3rd and 4th paryngeal pouch Baby is DiGeorge Syndormoe -> cause: 22q11.2 microdeletion - neural crest fails to migrate into derivative of 3rd (inferior parathyroid and thymys) and 4th (superior parathyroid) pouches -> path: parathyroid and thymic hypoplasia -> hypocalcemia and T cell deficiency (recurrent viral, fungal and protozoan infections) -> also results in conotruncal cardiac anomlaies - interrupted aortic arch, truncus arteriosus - from failre of neural crest migration Complication: additional involvement of 1st and 2nd pharyngeal/branchial pouches -> patients with DGS may have features such as hypertelorism, short palpebra fissures, micrognathia, bifid uvula, cleft palate

Infant is male but has hypospadias and small phallus. Testes are well developed but reside in inguinal area. Serum testosterine is normal. Karyotype is normal. Wgicg enzyme is deficient? a. 5 alpha reductase b. 17 hydroxylase e. DHEA sulfatase

5 alpha reductase Converts Testosterone -> DHT DHT influences development of: external male genitalia, growth of prostate, male pattern hair growth, amplifies effects of testossterone due to high affinity for test R -> 2 receptors: type 1 on post pubertal skina nd type 2 on genitals -> presentaiton: defect in external genital develoment due to lack of DHT -> male pseudohermaphroditism -> ranging from small phalus with hypospadias to ambiguous or female type genitalia Testosterone: Internal genitalia develop normally under influence of testosterone, spermatogenesis, male sexual differentiation at puverty (muscle mass, libido) Estrogen: endometrial proliferation, deelopment of ovarian granulosa cells, breast development

314 Exposure to carbon tetrachloride -> rapid and extensive liver dmage -> fatty change and hepatocyte necrosis. Changes are result of: a. abnormal signal transufction d. free radical injury e. mt dysfunction

CCl4 is ox by liver p450 -> formation of free radical CCl3 -> reacts with structural lipids of cell membrane -> lipid degradation and H2O2 formation -> lipid peroxidation -> peroxides form new radicals -> increased lipid degradation -> leads to swelling of EER, desucrtion of mt andincreased perm of cell membrane -> hepatocyte necrosis Mt dysfucntion occurs as reuslt of free readical inury

608 Woman being evlauated for chronic weakness an fatigue. Do a metyrapone stimulatin test. Shows increase in urinary 17-hydroxycorticosteroid (17-OHS) over time folling metyrapone administration. Which mechanism is most likely for this increase? a. ACTH surge c. cortisol overproduction

ACTH surge Metyrapone stimulation test is an indicator of HPA axis integrity - blocks cortisol synthesis by inhibiting 1 1 beta hydroxylase which converts 11 deoxycortisol to cortisol in ZF - low cortisol -> no inhibition of ACTH seetion -> icrease in pit ACTH secretion -> increase in 11 deoxy cortisol -> metabolised by 17 hydroxycorticosteroids that accumulate in the urine - serum 11-DOC and urinary 17-hydroxycorticosteroids normally rise in response to metyrapone -> indicates intact HPA axis - failure of steroid levels to increase implies primary or secondary adrenal insufficiency based on plasma ACTH c. leads to increase in cortisol not decrease

1713 Rectal admin of drugs:

Above dentate line -> venous drainage to portal circulation -> metabolized by liver Below dentate line -> venous blood to systemic circulation -> no metabolism by liver ->bypasses first pass metabolism -> increased bioavailabiliity of drugs otherwise metabolized by liver with oral administration

225 Man brought to ED with severe, sudden HA that started an hour ago. Pt reports mild HAs and decreased libido over the past 3 months. No other medical conditions and takes no meds. PE reveals bilateral deficits involving the temporal visual fields and impaired extraocular eye movemens. Shortly after being admitted to the hospital, he becomes acute hypotensive and loses consciousess. Pt. dies despite aggressive resuscitation efforts. Which is most likely to be found on autosy? a. acute hemorrhage in the pit gland b. ischemic necrosis of the pit gland c. ruptured intracranial aneurysm

Acute hemorrhage in pit gland Pit apoplexy - pt has features: severe HA, bitemporal hemianopsia, opthalmoplegia - usually occurs in a preexisting pit adenoma - as in this pt with chronic HA and low libido prob due to hyperprolactinemia Complications; - CV collapse due to ACTH deficiency and subsequent adrenocortical insufficiency - requires urgent treatment with glucocortiocoids B. ischemic necrosis of pit usually occurs in Sheehan syndrome due to hypoperfusion of enlarged pit during childbirth - presents with chronic hypopit - failure to lactate - severe HA and visual field defects do not occur C. ruptured saccular aneurusm near optic chiasm - presents similarly - but this pts chronic hx of decreased libido and acute CV collapse is more suggestive of pit etiology (possible arising from pit adenoma)

15105 15 yo boy has neck mass that has enlarged. Firm nontender mass in L thyroid love. Fine needle biosy reveals cluster of cells with abdundant cytoplasm staining postiive for calcitonin. Pt is also found to be positive for RET gemline mutation. Total thyroidectomy is planned. Prior to surgery, additional testing should be performed to evaluated for abnormality in which organ? a. adrenal cortex b. adrenal medulla c. anerior pit d. pancreatic islets e. thymus

Adrenal medulla Patient has MEN2 - cause: activating RET mutation -> RET protooncogene - has medullary thyroid cancer - both 2a and 2b - other associated cancerS: pheochromocytoma (both a and b), PTH hyperplasia (2A), mucosal neuromas and marfanoid habitus (2B) - pheochromocytoma is common to both 2A and 2B Ddx: MEN1: Cause: MEN1 mutation Associations: Anterior pit adenomas, Hyperparathyroidism (adenoma or hyperplasia) and neuroendocrine tumors of pancreas and GI tract - glstrinoma, insulinoma

1073 6 mo is lethargic and bomiting. Normal growth and developemtn. Exclusibely breasted until 2 days ago when homemade pureed food was added to diet -> no fever or diarrhea. Serum glycose is 30. Testing reveals aldolase B deficiency Which should be removed? a. amylose b. ceelulose c. galactose d. glucose f. maltose g. sucrose

Aldolast B metabolizes fructose 1 phosphate to DHAP and glyceraldehyde -> enter glycolytic pathway -> aldolase B deficiency can result in fructose 1 phosphate accumulation -> toxic metabolite depletes intracellular phosphate and inhibits activation of hepatic phosphrylase and gng -> hereditary frustose intolerance (fructosemia) is AR GNg is impaired -> hypoglycemia severe -> prx wth lethargy, sweating, vomiting, dehydration Need to refrains from dietary fructose and sucrose -> drmaatic recovry

How does serum pH affect calcium levels?

Alkalosis increases Ca binding to albumin -> decrease in serum Ca+

8330 Mechanism of human placental lactogen and gestational diabetes

Alos increases maternal lipolysis -> FFAs and ketones for mom energy + for baby in case of mom malnutrition Increaseing HPL as fetus grows and is greatest ni 3rd trimester when fetal growth is greatest. Oral glucose test and screening for gestational diabetes most accurate in 3rd trimester.

Difference between alpha antagonists and 5 alpha reductase inhibitors for BPH treatment

Alpha antagonists relax smooth muscle in bladder, prostate and prostatic urethra to encourage easier urination and end urinary symptoms - work quickly - days to weeks 5 alpha reductase inhibitors decrased DHT produciton and reduce prostate gland size itself - takes 6-12 months to wrok - SE: decrased libido and erectile dysfunction

15668 Pathogenesis of diabetic retinopathy

Chronic hyperglycmic injury to small retinal vessels - microangiopathic complication Process: 1. nonproliferative in early disease: - thickening of BM and failure of blood retinal barrier - increased permability allows leakage of fluid into retina (macular edema) -> distort vision and leave lipidrich depsoits = hard exudates - arteriolar obstruction -> ischemic injury to retina -> cotton wool spots - microaneurysms and dot blot hemorrhages due to aneurysm rupture 2. proliferative in advanced disease - retinal ischemia due to hyaline arterioscleoriis leads to angiogenic factor production (VEGF) ->formation of new vessels -> fragile and extend into adjacent vitreous -> traction can cause detachment of retina or laceration of the vessels - acute hemorrhage and vision loss

Diabetes pt has an increased fasting blood glucose. Recommends medicine that increases concentration of fructose 2,6 bisphosphate within hepatocyte. Whch conversion will be inhibited by high intracellular concentrations of this? a. acetyl coA -> fatty acids b. alanine -> glucose c. fructose 6 phosphate -> fructose 1,6 bisphosphate d. NAD+ -> NADH

B. alanine ->glycogen Fructose 2,6 bisphosphate helps control balance between gng and glycolysis through inverse regulation of phosphofructokinase and fructose 1,6 bisphosphatase F26BP activates PFK -> glycolysis -> F6P to F16BP F16BPase activates gng Interconversion of F6P and F26P achieved by bifunctional enzyme complex composed of PFK2 -> increases F26BP anf F26BPase -> decreasses fructose 2,6 bisphosphate and augmented glycolysis Insulin activates PFK-2 -> increased F26BP -> increased glycolysis High concentrations of fructose 2,6 BP inhibit gluconeogenesis -> decreased conversion of alanine and other gng substrates to glucose

989 Woman goes more than 24 hours without eating. She is dehydrated but has a blood glucose of 92. Which hormone binds to an intracellular receptor to help maintain this pt's lab findings within the normal range?

Cortisol Hormones that counterract hypoglycemia: 1. glucagon - gng and glycogenolysis 2. epinephrine - stimualtes glycogenolysiis and gng by increasing release of gng substrates from muscle and fat - limits glucose utilization by some insulin sensitive peripheral tissues 3.. cortisol - intracellular R binds to heat shock prtein and dimerizes -> bind to hormone responsive elements in promotr - increases transcription of gng enzymes + lipolysis and proteolysis 4. growth hormone - extracellualr JAK STAT transmembrane R that antagonizes insulin, increases gng and promote lipolysis (gng substrates) FA pg 330 review

A woman has a papilalry thyroid carcinoma. Thyroidectomy is planned. During surgety, nearby nerve is injured while ligating artery entering superior pole of thyroid lobe. Which muscle is likely to be denervated as a result of this injury? a. aryepiglotticus b. cricothyroid c. lateral cricothyroid

Cricothyroid Superior thyroid artery and inferior thyroid artery provide supply to thyroid and parathyroid Superior thyrid artery and vein and external branch of superior larygeal nerve course together in neurovascular triad that originates superior to thyroid gland and lateral to thyroid cartilage. - External branch is at risk of injury during thyroidectomy and it courses deep to superior thyroid artery -> innervates cricothyrid muscle -> tenses vocal cords and denervation causes low hoarse voice with limited range of pitch Internal branch of superior laryngeal does not innervate any muscles but provides sensory innervation to laryngeal mucosa above vocal folds Recurrent larungeal n. innervates all other laryngeal muscles and sensory innervation below the vocal folds

Individual with point mutation in gene responsible for neurphysin synthesis is liekly to suffer from? a. short stature b. hyperpigmentation c. DI d. hypothyroidism e. infertility

DI Neurophysins are carrier proteins for oxytocin and ADH produced within PV and SO nuclei in hypothal -> bind hormones and act as chaperone molecules as they are shuttled towards nerve terminals in posterior pituitary Neurophysin 2 has specific binding site for vasopressin -> involved in transport and packaging of vasopressin through ER and golgi apparatus into neurosecretory granules -> point mtation in neurphysin 2 could result in abnormal protein folding and remocal from ER along with bound vasopressin -> decreased availability of vasopressin for neurosecretory release -> possible mechanism for AD hereditary hypothalamic diabetes inspidius

924 How does hypoaldosterinism cause decreased bicarb and increased Cl-?

Decrease in H+ excretion -> nonanion gap metabolic acidosis with low plasma HCO3- -> compensatory Cl- reention to maintain electrical neutrality of extracellular fluid

Pattern of PTH, urinary calcium, 1-25 dihydorxyitD in thiazide diuretics

Decrease in urinary calcium due to icnreased absorption, leads to decreased PTH and normal vit D

Why is atropine given prior to bronchoscopy?

Decrease resp. mucuous secretins and promote bronchodilation Elderly at risk of toxicity due to decreased renal and hepatic clearance

920 Peroxisome proliferator activated receptor gamma - nuclear receptor and trans factor is used for diabetes. Activation of this receptor would result in which change? a. decreased insulin resistnace b. downregulation of adiponectin c. increased FFA level d. increased insulin release e. upregulation of leptin activity

Decreased insulin reistance Thiazolidinedione (TZD) decreaed insulin resistance - bind to PPAR gamma (trans regulator of genes in glucose and lipid metablism) -> binds trans regularory sequences of target genes -> 1. GLUT4 transported upregulation increases insulin dependent glucose uptake by muscle and fat cells 2. adiponectin - cytokine secreted by fat that increases number of insulin responsive adipocytes that stimualtes fatty acid oxidation Similar to fibrate meds

26 yo woman has generalized weakness, myalgias and unintentional weight loss. Has primary hypothyroidism and takes T4. BP is 110/70 supine and 90/60 standing. Mildly emaciated. Mild normochromic, normocytic anemia, eosinophil count of 15% and serum glucose of 65. Which additional changes is most likely in this patient? WHat will be the serum and urine Na and K?

Decreased serum Na+ and increased serum K+ (lack of aldoesterone) Increased urine Na+ and decreased urine K+ Patient has primary adrenal insufficiency or Addison's disease Cause: most liely autoimmune destruction of bilateral adrenal cortex and occurs in patients with preexisting history of autoimmune disease Path: decreased aldo pridction -> renal salt wasting and hypovolemia an orthostatic HTN + decreased cortisol = hypoglycemia, normocytic anemia and eosinophilia

19 yo man has weakness and confusion - polyuria and polydipsia and increased appetite for last 2 weeks. Breath has fruity odor, 90/60 bp, pulse is 97 and respirations are 22. Patient is deficient in a hormone that normally performs which of the following actions? a. activates hormone sensitive lipase b. decreases glucagon secretion c. decreases muscle glycogen synthesis d. increases hepatic glucose production e. increases renal glucose reabs

Decreases glucagon secretin Pt is in DKA due to insulin deficiency -> hyperglycemic So the answer is an action that insulin usually performs Insulin normally suppresses glucagon secretion and vice versa A. Insulin downregulates hormone sensitive lipase to release FFAs (lack of inslin upregulates lipolysis for lipid derived energy -> weight loss) - -> lipolsis is stimulated by ACTH and epinepherine C. insulin increases glucose uptake by muscle -> increases muscle glycogen synthesis (also increases AA transport and ribosome tranlstion efficiency in muscle tissue -> increase in protein synthesis) D. insulin functions to decrease hepatic glucose production (not increase) -> decrease blood glucose E. renal glucose reabs occurs independent of glucose and is mediated by SGLT2 co transporter in PCT

Other than increasing expressing of RANKL on osteoblasts, how does PTH stimualte osteoclasts?

Decreases production of osteoproteregin, a competitive antagonist of RANKL on osteoblasts, so osteoblasts are more likely to bind RANK on osteoclasts and activate

55 yo woman comes to physician with swelling around her ankles and face that has worsened over last 1-2 monthss. Patient has 2+ bilateral pitting edema in lower extremities, trace edema in upper extremities and periorbital eema. Cardiopulm exam is normal. Lab shows increased serum Cr and low albumin, Urinalysis shows 3+ proteinuria and no hematuria or casts. Kidneyniopsy shows.... What is the cause of finding? a. bee sting with severe allergic reaction b. diabetes mellitus c. hepatitis C infection d. HIV e. SLE

Diabetes Biopsy shows Kimmelstein-Wilson nodules characterized by: - location in mesangium - ovoid or sphere shape - lamellated - eosinohilic -PAS positive KW noduels -> nodular glmoerulosclerosis -> glomerular BM thickening and increased mesangial matrix deposition -> expansion of mesangium and KW nodule formation compress capillaries and cause loss of gllomuerlar function - patients have proteinuria that leads to overt nephrotic syndrome - pierpheral edema, proteinuria, fatty casts, HTN and renal failure - urine sediment is bland - nodular glomeruloscleoriss is caused by diabetic nephropathy - indicates irreversible glomerular damage and predicts rapid decline in kidney functoin

What are the histo findings in Graves disease?

Diffusely enlarged thyroid** - tall crowded follicular epithelium with hyperactive reabs -> scalopping around colloid edges Ddx: follicular hyperplasia with elongated epithelial cells in tall cell variant of papilalry thyroid cancer in older adults

12101 Pathogensis of hypercalcemia in multiple myeloma

Due to tumor infiltration of the bone marrow -> osteolytic cytokine (TNF alpha) activation -> liberate Ca from bone and result in hypercalcemia which results in -> hypercalciuria and renal insufficeincy due to nephrocalcinomsis and Ig light chain nepropathy -> low vit D due to low PTH

Hepatocytes are centrifuged to remove membrane components and organelels. FOllowing subseuqentrounds of centrifugation -> remaining supernatant contains cytosol and cytosolic proteins -> whiceh enzymes will likely be detectable in supernatant of healthy liver cells a 3 hydroxy 3 methylglutaryl coA lyase b. ornithine transcarbamylase c. pyruvate carboxylase d. succinate dehydrogenase e. transketolase

E. transketolase Mt processes: fatty acid ox, TCA, carboxylation of pyruvate (gng) Cytosol: glycolysis, FA synthesis, pentose phospahte pathway Both: heme synthesis, urea cycle, gng Transketolase is PPP enzyme that uses thiamine as cofactor to shuttle 2 carbon fragments between sugar molecule

What do thyroid follicular and parafollicular cells derive from?

Endoderm

988 22 yo has a neck mass - 2 cm nodule in R lobe of thyroid. Mulitple 4 to 8 mm soft papules on lips nd tongue. Arm span exceeds height and patient has long fibers. Serum calcinotnin is elevated. What is most likely ro develop in pt? a. episodic headaches c. hypoglycemic episodes d. peripheral vision loss e. recurrent peptic ulcers

Episodic headaches MEN 2B: - medullary thyroid cancer -> increased calcitonin - marfanoid habiitus -mucosal neuromas - last associated one: pheochromocytomas - intermittent secretion of catecholemaines -> increwas BP -> episodic headches + diaphroesis, chest pain, tremor, anxiety Cause: RET oncogene mutation in germline C and E. Indicate pancreatic tumor that secretes gastrin (zollinger ellision) -> refractory peptic ulceration and or insulinoma - hypoglycmiea - associated with MEN1 D. peripheral vision loss due to pit tumor - also in MEN 1

How does estrogen and TRH affect proloactin release from ant pit?

Estrogen stimulates prolactin gene transcription and secretion TRH stimualtes secretion of prolactin by lactotrophs - role in regulating prolactin release is secondary to inhibition of prolactin secretion by dopamine - increase TRH -> hyperrpolactinemia

HIV associated lipodystrohy results in what changes in ghrelin, leptin and insulin

increase ghrelin and insulin decreased leptin

1163 Why does Cushing's disease result in hyperplasia of zona fasiculate and reticularis but not glomerulosa?

Excess ACTH increased adrenal bllod flow and metabolic acfitivty within fasiculate and reticularies. -> stimulates transfer of cholesterol to inner mt membrane by steroidogenic acute regulatory protein - rate limiting step in steroid production and conversion to pregnenolone by cholesterol side chain cleavage enzyme -> increased pregnenolone -> increased cortisol and androgen production + trophic effect -> high ACTH upregulates RNA and protein synthesis-> hperplasia Increased ACTH can have transient effect on aldo production but Ag2 is primary trophic hormone for ZG -> hyperplasia or adenoma of ZG can be asssociated with icnreaed secretion of MC (Conn synrome)

What is the role of fibroblast growth factor in calcium homeostasis?

FGF acts synergistically with PTH to increase phosphate excretion by downregulating sodium/phosphate cotransporter gene expression in proximal renal tubule -> FGF inhibitors decrease phosphate excretion FGF also inhibits 1 alpha hydroxylase -> less calcitriol production

Mechanism of long acting basal insulin?

Forms insoluble complexes at the injection site - this forms microprecipitates at the injection site that then slowly dissolve and are released into circulation throughout the day

1839 What is the mechanism of amenorrhea in anorexic patients?

Funtinal hypothalamic amenorrhea (secondary) - decrease in circulating leptin due to decreased adipose stores -> inhibits pulsatile GnRH release from hypothal -> decreased LH and FSH release -> low circulating estrogen and amenorrhea Can also occur if caloric expenditure is > intake: thin female athelets or pts with chronic illness Complications: reduced peak bone mass -> early onset osteoporosis Vs. primary amenorrhea - ffailure of menarche b age 15

Researchers measure serum insulin of volunteers sfter equivalent load of oral and IV glucose. Increased insulin release after oral glucose compared to IV, which endogenous substance explains the difference between the curves? a. IGF-1 b. GLP-1 c. somatostatin d. secretin e. CCK

GLP-1 Incretins are GI hormones produced by gut mucosa that stimulate pancreatic insulin secretion in response to sugar containing food -> response is independent of blood glucose levels and aoccurs prior to any elevation in glucose following a meal -> GLP-1 and GIP (gastric inhibitor peptide/glucose dependent insulinotropic peptide) are 2 incretins Insulin increases gollowing IV glucose due to pancreatic beta cell sensitivity to blood glucose but not as much of an icnrease due to lack of incretin effect from GI tract

14952 Leuprolide MOA

GnRH analog used to supresses testosterone or etrogen in prostate or breast cancer 1. given pulsatile -> agonist of sex hormones 2. given continuously -> activates negative feedback and leads to downregulation of GnRH R on gonadotropin cells in pituitary -> suppresses pit LH release and leads to reduced production of testosterone by Leydig cells. -Lower levels of circulating testosterone produce clinical effect similar to orchiectomy

In what kind of diseases can you have elevated vitamin D?

Granulomatous disease due to expression of 1 alpha hydroxylase from activated MOs -> increased calcitriol formation -> TB, sarcoidosis -> similar process in Hodkin disease and some non-hodgkin lymphomas

767 How does potassium iodide work?

High serum levels of nonradioactive iodide can competitively inhibit radioactive Iiodine 131 from entering thyroid follicular cells. Large increases in serum iodide levels also inhibit iodine organification -Wolf Chaikodd effect and reduce TH release

34 yo man develops DI. Started on ADH. Over next 2 years, try multiple times to take him off medication by symptoms would always retur. This is explained by damage to what?

Hypothalamic nuclei NOT posterior pit ADH is synthesixed in hypothal and release by posterior pit If injury was in poterior pitatuiary distal to hypothal then it would be transient DI because mangocellualr neurons are intact and can produce more ADH -> magnocellualr injury of hypthal causes permanent central DI

821 Collection of tan fat containg tissue is found around kidneys and adrenal glands of newborns during surgery. Surgical removal of tissue would contrubte to? a. fasting ketonemia d. lactic acidosis e. hypothermia

Hypothermia This is brown adipose which is 5% of body mass is neonates -> main function is heat production -> purpose: neonates are more sus to hypothermia due to immature nervous system -> high body surface area to volume ration and decreased ability to shiver for heat production Vs white adipose - cells that contain one intracytoplasmic fat droplet ->> brown adipocytes possess several small intracytoplasmic fat vaculoes and more mitochondria (which gives brown color) -> high O2 requirement and more capillaries than white adipose tissue -> brown fat has uncoupled electron transport and phosphorylation -> protons pumped out by electron transport chain return to matrix via mitochondrial membrane protein thermogenin -> uncoupling protein -> no ATP synthesis -> energy released by electron transport is dissipated as heat (NOT ATP)

Why do you have hyponatremia in primary adrenal insufficiency?

Hypovolemia in PAI stimualates ADH secretion -> dilutes serum and results in hyponatremia Tubular salt wasting by aldo deficiency does not directly affect serum sodium concentration

Which protein lacks a signaling sequence and is secreted directly from the cytoplasm across the plasma membrane?

IL-1

600 what is the difference between giving regular insulin IV and subcu?

IV given for hyperkalemia, DKA, stress induced hyperglycemia and has a half life of 5 minutes so works rapidly SUbcu is for subactue and chronic management of dibates in combo with intermediate acting or long acting analog -> when given subcu 0> polymerizes into hexamers -> delays absorption -> starts working in 30 minutes, peaks in 2-4 hours and lasts 5-8 horus

What causes hyperestrinism in cirrhosis?

Impaired hepatic degradation of estrogen + ethanol directly inhibits testosterone production + decreased clotting factor production -> increased PT/INR

What is reverse T3 and how is it produced?

Inactive form of T3 produced directly from T4 deiodination (cannot be produced by T3) So if T4 is decreased, reverse T3 will also be decreased

Pattern of PTH, urinary calcium, 1-25 dihydorxyitD in familial hypocalciuric hypercalcemia

Inapprop Normal or increased PTH, decreased urinary calcium, normal 1,25 hydroxyvit D Defect in Ca+ sensing receptors in nephron and PTH glands - PTH cannot be surprisedd by hypecalcemia in blood - urinary calcium is decreased bc PTH stimulation is reabsorbing it in DT - vit D is normal because PTH is normal or increased

Pattern of PTH, urinary calcium, 1-25 dihydorxyitD in granulomatous disease

Increased 1,25 vit D, increased urinary Ca (due to increased filtered Ca+ load), increased Ca abs in intestine and decreased PTH due to increased Ca+ from vit D

547 What is aldoesterone escape in primary hyperaldeosteroneism (Conn sndrome)?

Increased aldo -> increased intravasc volume -> increased RBF with resulting pressure natriuresis -> augmented release of ANP -> increased sodium excretino by renal tubules -> limits net sodium retnetino and prevents development of overy volume overload and hypernatremia

15201 Adults without diabetes were put on a low cal diet and moderate intensity exercise program. Blood samples to study changes show what change in ghrelin, leptin and insulin?

Increased ghrelin, decreased leptin and decreased insulin Weight regulation hormones: 1. ghrelin - produced in stomach in response to fasting - stimualtes appetite 2. leptin - produced by adipose in response to short term food intake and long term adequate of fat stores - acts on hypothalamus to decreased appetite - blunted by obesity - leptin levels fall in fasting state (+ with decreased adipose) 3. insulinin - decreases appetite - increased levels in obesity (insulin resistance) - weight loss associated with greater insulin sensitivity and lower insulin levels In these pts: caloric resitriction and falling fat stores - increased ghrelin - decreased leptin (less adipose) - decreased insulin (weight loss)

772 52 yo woman has menopausal symtpoms. Started on combo estrogena nd progesterone 2 months ago. Symptoms improved. What change in thyroid function occurs as result med use? a. decreased TSH level d. increased free T3 e. increaed free T4 f. no change in thyroid hormone levels

Increased total T4 Thyroid is in 2 forms: protein bound and free - free enters target cells via carrier mediated mech - most is bound to plasma proteins -> large circulating reservoir of TH - thyroxine binding globulin - 70% of binding, with additional share by albumin and transthyretin Increase in estrogen -> increase in circulating TBG -> decrease in free T4 and T3 -> reudction will result in transient increase in TSH -> increase in TH production until additional TBG becomes saturated with TH and free T4 and T3 are resotred -> increase in TBG -> increase in total T4 (bound plus free) + T3 - level of free thyroid hormones remains normal - patients are euthyroid and TSH levels return to normal

1997 Mechanism of botulinum toxin?

Inhbiits cholingergic nerves - nicotinic and muscarinic MOA: enters nerve terminals through endocytosis -> prevents binding adn fusion of Ach containing synaptic vesicles with plssma membrane via destruction of SNARE proteins - blocks Ach release into synapse - heat labile - prevented by thoroughly heating food prior to consumption - highly portent - small quantity can be lethal without ventilatory support

Man has genetic abnormality that leads to permanently inactive FSH receptors. Which substance is most likely decreased in this patient? a. FSH b. LH C. inhibin B d. testosterone e. DHEA

Inhibin B FSH stimulates inhibin B production and sertoli cell production of androgen binding protein locally within seminiferious tubules -> androgen binding protein is responsible for high local testoesterone concentration and is different from SHBG -> high testosteorne and FSH needed for spermatogenesis -> defective FSH receptors will prevent spermatogensis and cause low inhibin B levels because FSH is responsble for its production

21 yo man undergoes routine pre emloyment physical. He is found to have only 1 testis in his scrotum. Further eval reveals elevated serum FSH and normal serum LH. Production of which substance is likely to be impaired in patient? a. testosterone b. DHT c. DHEA d. inhibin B e. cortisol

Inhibin B Pulsatile GnRH from hyopthal -> FSH and LH release from pit -> LH stimulates release of testosterone from Leydig cells of testes and SH stimulates release of inhibin B from sertoli cells of testes -> testosterone inhibits release of GnRH and LH and inhibin B inhibits release of FSH Sertoli cells are present in seminiferous tubules of testes -> reduced in patients with 1 testicle -> circulating levels of inhibin B are likely to be low in these patients -> no adequate negative feedback so FSH is increased **need to be evalted bc increased cancer risk in men with undescended testicle - must be removed (orchiectomy) or receieve surgety that allows descent into scrotum (orchiopexy)

1325 19 yo man comes to office - frequent episodes of disorientation, palpitations, tremulousness, excessive sweating for last 3 months. Symptoms resolve after drinking juice or carbonated beverage. Diagnosed with type 1 DM and takes short and long acting insulin. Reports stress due to upcoming midterm. Lab shows HgbA1c of 6.8 and no proteinuria. Which factor preciptiated current symptoms? a. fructose rich drink b. intense exercise c. mental stress d. resp infectoin e. sleep deprivation f. weight gain

Intense exercise Patient has symptomatic hypoglycemic episodes relieved by glucose despite no changes to chronic insulin regimen which can be caused by: 1. insulin overdose 2 decreased carb intake (skipped meal) 3. intensive physical activity or exercise Glucose uptake by skeletal muscle cells via GLUT4 -> translocated to cell membranes and traverse tubules (deep invaginations in cell membrane) in response to insulin and insulin-independent mechanism by muscle contraction (exercise) - mediated by cellular factors (AMP kinase, NO, calcium calmodulin activated protein kinase) - occurs bc muscles need more glucose for energy during exercise In normal individuals, hypoglycemia does not occur with exercise because drop in blood glucose suppresses insulin release from beta cells and glucagon increases to counter regulate and increase glucose production via glycogenolysis and gng Patients on exogenous insulin are vulnerable to exercise-induced hypoglycemia because insulin continues to be released by long-acting insulin despite glucose uptake by skeletal muscle cells Vs. Infection, pain, sleep deprivation, and severe mental/emotional distress cause hyper rather than hypoglycemia due to increased production of counterregulatory hormones (catecholamines, cortisol)

Which enzyme removes iodine groups from MIT and DIT from thyroglobulin bound?

Iodotyrosine deiodinase

7651 Man has acromegaly. Which is most likely to be associated with condition? a. aortic root dilation b. biscupid aortic valve c. LV hypertrophy d. mitral valve prolapse e. pericardial effusion

LV hypertrophy CHronic GH stimulates cardiac growth -> LV hypertrophy, diastolic dysfunction and possible heart failure + joint athryopathy due to hyperplasia of articular chondrocytes, synovial hypertrophy-> wear and degeneration of articular cartilage and periarticular bone a. aortic root dilation + mitral valve prolapse - Marfan syndrome due to cystic medial degeration b. Ehlers danlos syndrome is associated with biscupid aortic valve or mitral/tricuspid valve prolapse due to deect in lysyl hydrozylase and collagen crosslinking -> hyperextensivle fragile skin and valves -> pectus excavatum, scoliosis, hypermobile joints e. untreated hypothyroidism - pericarial effusion and myxedema (nonpittin edema) due toe xcess deposition of mucopolysaccharaides and adipogenesis in dermis adn subcu tissues

849 WHat is the key organ and process stimulated by glucagon?

Liver - glycogenolysis Glucagon funcions by stimulating GPCR on liver cells -> increase in intracellular cAMP concentration and activation of protein kinase A -> activation of key glycoenolytic enzyme - glycoen phosphorylase -> also stimulates gng enzymes and decreases F26bP to inhibit glycolysis Vs. Epinpehrine - increases glucose by glycogenolysis and gng in liver and decreased glucose uptake in skeltal muscle + increased alanine release from skeletal muscle -> source of gng in liver. In Adipose -> epi increases lipolysis and increased FFA and glycerol that can be utilized as gng substrantes

223: Why does estrogen result in loss of bone mass?

Low estrogen -> increased production of inglammatory cytokines (IL-1 and TNF-alpha) -> increasing expression of receptor activator of NFkB ligand RANKL -> increasing osteoclast activity

8 month old has developmental delay, failure to trhive and seizures. Exam shows hypotonia and opthalmoplegia and elevated serum lactate. Severely reduced pyruvate hydrogenase enzyme activity in freshly isolated peripheral blood lymphocytes and cultured fibroblasts. increasing which substance in his diet will help genereate energy without further leevating lactate levels? a. alanine b. asparagine c. galactose d. glycerol e. lysine f. serine

Lysine Has pyruvate dehydrogenase deficiency -> inherited inborn error of metabolism -> PDH complex generates acetl coA from pyrivate - linking glycolysis and TCA cycle -> dietary carbs are broke down into pyruvate via glycolysis -> lack of enzymatic activity of PDH leads to pyrivate buildup -> shunted to lactate via lactate dehyrogenase -> lactic acidosis Disease management involves implementation of ketogenic diet: high fat, low carb diet with moderate protein -> forces production of ketone bodies fromfat and AA catabolism to fuel the body in place of glucose -> near absence of glycose in diet decreases pyrivate -> decreases lactate AA catabolism results in intermediates referred to as glucogenic, ketogenic or both -> glucogenic AA metabolism produces pyruvate or TCa cycle intermediates -> glucose via gng -> ketogenic generates ketone body precyrsor acetyl coA Lysine and leucine are exclusively ketogenic

1819 Multidrug resistance gene

MDR1 gene codes for P glycoprotein transmmebrane protein that is an ATP dependent efflux pmp-> normally expressed in intestinal and renal tubular epithelial cells adn functions to eliminate foreign compuds from body -> protien is present in capillary endothelium of vessels that form BBB -> P glycoprotein prevents penetration of forign compounds into CNs -> I tumor cells:removes chemohearpeutic agents particularly hydrophoic anthracyclines

11918 Research studying metabolic pathways in obesity feeds experimental animals high carbm high protein diet. Sample of liver tissue is obtained and activity of various enxymes in FA metabolism is measured and recorded. Determined that B ox is inhibited in thise cells asa a result of diet. Increase in which substance is most response for effect? a. carnitine b. citrate c. malonyl coA E. nadph

Malonyl coA In well fed state -> abundance of ATP in hepatocytes ihibits isocitrate dehydrenase -> high citrate levels in mt-> high levels of citrate in mitochondria -> citrate to cytosol via citrate shuffle -> cleaved by ATP citrate lyase to form acetyl coA -> high citrate levels causes upregulation of acetyl coA carboxylase -> malonyl coA = RLS in fatty acid synthesis -> catalyzes condensation of malnyl coA with acetyl coA to create 4 carbon molecule that will undergo subsequent condensation reactions to form 16 C FA -> beta ox of FA takes place in mt matrix -> imerpeable to FA due to negative charge so carnitine carrier is needed to shittle to matrix Increased Malonyl coA inhibits carnitine acyltransferase -> preventing transfer of acyl groups into mitochondria -> inhibitory actions prevents breakdown of newly synthesized FAs

1327: Why is waist circumference associated with insulin resistance?

Measures visceral fat - surrounding internal organs -> correlates strongly with insulin resistance versus subcutaneous fat - measurement of waist circumference or waist to hip ratio Metabolic syndrome: increased waist size, HTn, serum lipid abnormalities

Boy has ectopic sublingual thyroid. Which embroy process failed?

Migration Gland is fomed from evagination of pharyngeal epithelium and descends to lower neck anterior to upper trachea and larynz -> lowest part of evagination forms thyroid gland and remaining porteion forms thyroglossal duct -> extends from foramen cecum on dorsal tongue to superior border of thyroid Failure of migration -> thyroid can be anywhere along thyroglossal duct path -> symptoms of lingual thyroid: obstructive especially during times of thyroid stimulaition -> if this is the only thyroid tissue inthe body pt can have hypothyroidism once it is remved

768 Woman has pain at front of her neck that is worse when swalling and decreased radioactive I uptake secondary to flu like illness. Which path change? a. branching papilalry structures with interspersed calcified bodies b. extensive stroma fibrosis beyong thyroid capsule c. follicular hyperplasia with talle cells forming intrafollciular papilalry projects d. mixed cellular infiltrate with multinuclear giant cellse. e. mononuclear parenchymal infiltration with well developed germinal centers

Mixed cell infiltirate with occaisonal multinucleated giant cells Pt has subacute grnauloamtous thyriditis (de Quervain) - follows viral illness - path: cross reacting immune response against viral proteins or tissue antigens released during cell injury - may be transient hyperthyrid phae due to increased relaase of stored thyrid hormone 0 decrased radioiodine tuptake - slef limited and resolved

Glucocorticoid effect on blood counts

Neutrophilia due to demargination of cells attached to cell wall Basophils, eosinophils, B cells and T cells decrease (especially T cells) - T cells decrease due to inhbiiton of IG synthesis, stimulation of lymphocyte apoptosis, and lymphocyte redistribution (from intravascular compartment to spleen, lymph nodes and bone marrow) Also inhibit peripheral extravasation of monocytes and MOs and decreased Ag presentation by MOs and dendritic cells - decreased in blood monocytes due to redistribution

929 30 yo woman has high BP. Low plasma renin and normal serum Cr. CT scan shows solitary hypodense R adrenal mass. Which serum elctrolyte pattern would most likely be seen in patient? a. high Na, low K, low bicarb b. low sodium, hihg K, low bicarb c. low Na, low K, high bicarb d. normal Na, high K, low bicarb e. normal Na, low K, high bicarb

Normal Na, low K, high bicarb High bp, low renin suggests primary hyperaldosteronism - unilateral arenal adenoma: Conn syndrome - bilateral renal hyperlpasia - idiopathic Hyperaldo is characterized by increased Na+ reabs from collecting tubule - creates negative charge in lumen -> pulling K+ and H+ from tubular cells -> increased excretion of urinary K+ and H+ -> hypokalemia and alkalosis - H+ excretion by alpha intercalated cells promotes bicarbonate production and increases activity of basolateral HCO3/Cl- exchanger -> incrased bicarb Hypernatremia and pedeal edema are rarely observed due to aldo escape: increased volume causes increases renal blood flow -> pressure natriuresis and augmented release of ANP -> limites net Na retention and prevents devleopment of overt volume overload and hypernatremia

1912 pathophys of diabetic nephrpathy

Normal glomerular BM has negatively charged heparan sulfate moieties that form charge barrier preventing negative charged proteins like albumin into Bowman capsule Diabetes: progressive loss of negative charge of BM due to upregulation of heparanase expression by renal epithelial cells leading to leakage of albumin and other plasma proteins Albuminuria increases as disease progresses Trx by: ACE inhibitors to reduce urinary albumin excretion and slow progression of diabetic nephropath

How do OCPs treat PCOS?

PCOS is associated with elevated androgen levels due to high LH (LH:FSH > 2) Exogenous estrogens/progesterones(usually combined OCP) -> negative feedback -> decrease LH secretion -> decrease ovarian andreogen production by the theca cells - also increase sex hormone binding globulin synthesis by the liver -> decreases free testosterone bc testosterone has higher affinity for SHBG than estrogen -> increased estrogen:androgen ration in serum

1845 34 yo man comes to clinic due to frequent clumsiness. For lst 6 months, repeated minor injuries from walking into doorways and objects. Hx notable for recurrent renal stones. Underwent dfinitive neck surgery. FH is unavailable as patient is adopted. PE shows bitemporal visual defects. CN, motor strength and DTR are normal. In addition to brain imaging, patient should also be screened for which tumor? a. adrenal b. bone c. breast d. colonic e. pancreatic

Pancreatic MEN1: - cause: mutation in MEN1 tumor suppressor gene - tumor of ps: parathyroid, pituitary and pancreas - 1. primary hyperPTHism uaully initial manifestion -> asmpyomatic hypercalcemia or renal stones 2. pituitary secreting adenomas - prolactinoma most common - women: menstrual irregularity, galactorreha - men: late visual bitemporalism or headache due to mass effect 3. Pancreatic neuroendocrine tumor: usually gastrinoma, can be insulinoma or nonfunctional - metastatic - tumor related death is common Pt has signs of pituitary tumor, of previous hypercalcemia (PTH) and should be screened for pancreatic tumor

454 Woman has a tumor of the zona glomerulosa. Pt would present with wchih additional symp? a. diarrhea and flsuing b. excessive hair growth c. paresthesias and muscle wakness d. sweating and tremulousness e. weight gain and easy brusing

Paresthesias and muscle weakness Primary hyperaldo -> potassium wasting and metabolic alkalosis -> hypokalema leads to paresthesias and muscle wakness

612 Woman comes to office with progressive weight gain and fatgue for 4 months. Also has increased difficulty in liting heavy objects and climbing stairs. Pt has moderate, perisstent bronchial asthma and uses inhaled steroids and beta 2 agonist. Increased BP and glucose and 24 hour urinary cortisol. High dose but not low dose dexamathsone supresses serum cortisol. Serum ACTH are high normal. What is cause of pt symptoms? a. adrenal adenoma b. adrenal carcinoma c. exogenous steroids d. pit adenoma e. small cell lung cancer

Pit adenoma In normal: low dose dexamethsoem supresses ACTH and cotsiol through negative feedback ACTH is high to inappropriately nrmal in this pt - hgh cortisol so ACTH should be low - if high dose dexa supresses -> ACTH secreting pit adenoma is likely -ectopic ACTH production is not supressed by high dose dexa (from SCLC)

1492 62 yo woman had a fall and needs hip surgery. Hx of diabetes, HTN, hyperlipidemia and migraines. Pt receives combo of long and short acting insulin. On surgery morning, fasting BG is 42.The paitent is awake and alert and says she feels hungry but has no other symtpoms of hypoglycemia. Concurrent use of which med explains this finding? a. atorvastatin b. doxazosin c. HCTZ d. losartan e. propanalol f. verapamil

Propranolol Counterregulation to hypoglycemia includes SNS activtion -> Epi/NE release -> glucagon, cortisol and GH release Symptoms of hypoglycemia: 1. neurogenic (autonomic) - mediated via Ne and EPI and ACH relaese due to SNS stimulation -> tremulousness, tachycardia, anxiety and arousal caused by NE/Epi and sweating, hunger and paresthesias aused by Ach 2. neuroglycopenic symptoms - inadequate glucose in CNS -> beahvioral changes confusion and visual disturbances, stupor, seizures Patient has reduced awareness of hypoglycemia due to nonselective Beta blocker use for HTN or migraines - decrease NE/Epi symtpoms of tachycardia, anziety, aroulsal due to SNS blockade - cholinergic symptoms - hunger are unaffected Nonselective beta blockers can also exacerbate hypoglycemia - epi stimulates gng and peripheral glycogenolysis but effect is diminished in beta blockers Remember: alpha 2 decreases insulin secretion, beta 2 increaes insulin secretion Statins and HCTZ cause hyperglycemia Rest have no effect on glucocse

1686 Nervous structure in close prox to inferior thyroid artery is damaged. What was it? a. accessory nerve b. ansa cervicalis c. hypoglossal nerve d. phrenic nerve e. recurrent laryngeal f. sueprior cervical ganglion g. superior laryngeal nerve

Recurrent laryngeal nerve Inferior thyroid a arises from thyrocervical trunk, branch of subclavian a. -> suppleies thyrid and structures of anterior neck with superior thyroid a. -> courses deep to internal jugular, vagus n and common carotid a before turning towards the thyroid -> artery comes in clsoe prox to recurrent laryngeal nerve prx: haorseness if unilateral, bilateral - inspiratory stridor and respiratory distress due to compelte vocal cord paralysis

607 MOA of metformin

Reduces hepatic gng by: - inhibition of glycerophosphate dehydrogenase and complex 1 in ETC - upregulation of AMP activated protein kinase - reduces availability of substrates for gng - dihydroxyacetone phosphate pyruvate, fatty acids and increases peripheral glucose uptake and utilization SE: - inhibition of gng enzymes results in buildup of substrate molecules such as lactate -> increased risk of lactic acidosis mainly in those with renal dysfunction which causes decreased lactate clearance - should estimate GFR via serum creatinine prior to initiation of metformin therapy

1296 24 yo woman G1P0 comes to L&D triage at 28 weeks gestation due to intense abdominal pain, vaginal bleeding, decreased fetal movement. Normal temp increased bp. Exam shows terse abdomen and firm tender uterus. US shows hematoma between placeta and uterine wall and no fetal cardiac activity. Lab results show decreased platelets, Hgb and normal AST/ALT. Patient is hospitalized and stats bleeding from vagina, guma, and IV line sites. Blood in foley catheter. Which is causing her bleeding? a. amniotic fluid in maternal circulation b. bacterial infection of endometrium d. release of tissue factor into maternal circulation e. rupture of uterine endometriumm myometrium and serosa

Release of tissue factor into maternal circulation** Patient is in DIC - life threatening in OB due to massive activatio of clotting cascade - risk factors: placental injury (abruption), sepsis, pp hemorrhage and acute fatty liver of pregnancy and amniotic fluid embolism - in preg: DIC mediated by tissue factor (thromboplastin) release from sites of placental injry -> initiating coag cascade ->excessive productin of thrombin and widespread intravasc fibrin deposition and fibrinolysis. Clotting factors and platelets are rapidly consumed -> profound bleeding from incision sites, IV line sites and mucosal srufaces This pt presents with abruption - vaginal bleeding, uterine tendernes, retroplacental hematoma and fetal demise - may result from severe HTN (in this pt) - most common cause of DIC in pregnancy a. Amniotic fluid in maternal circulation - amniotic fluid embolism can result in DIC but is associated with hypotension and cardiogenic shock vs. HTN b. Sepsis caused by infections such as endometritis or chorioamnionitis can lead to DIC -> usually accompanied by fever and low BP e. uterine rupture occurs in patients with history of uterine surgery and preents with vaginal bleeding,a cute abdominal pain and loss of fetal station -> includes palpable fetal parts protrudicnt thrugh disrupte myometrium

HOw is insulin metabolised?

Renal and heaptic CKD -> increased insulin -> increased hypoglycemia

MEN 2 is associated with which oncogene and which cancers?

Ret proto oncogene 1. pheochromos 2. medullary thyroid cancer - malignancy of parafollicular C cells 3. parathyroid hyperplasia (2A) or mucosal neuromas and marfanoid habitus (2B)

Which is major inciting factor responsile for diabetic patient's foot ulcer?

Sensory impairment due to peripheral neuropathy due to osmotic damage Loss of protective senses -> not recognize an injury due to minor trauma or pressure -> woulnd in plantar surface of first metatarsal head often goes unnoticed Loss of prprioception and increase in ligamentos laxity can cause chronic pressure induced joint/skin damage in feet of patients with diabetic neuropathy -> calluses or foot deformities

What is the most preventable cause of death and disease in the US?

Smoking cessation Increaes complications of diabetes + risk of developing in the first place

631 Women has recurrent renal colic. passes 2 urinary stones in last 2 years and most recent was calcium oxalate stone. Patient ahs diffuse aches and pains and history of peptic ulcer disease for which she takes famotidine daily. Lab results show hypercalcemia and hypophosphatemia with increased 24 hour urinary calcium excretion. Which change in bone structure is associated with patient condition? a. lamellar bone structure resembling mosaic pattern b. osteoid matrix accumulation around trabeculae c. spongiosa filling medullary canals with no mature trabeculae d. subperiosteal resorption with cortical thinning e. trabecular thinning with few interconnections

Subperiosteal resorption with cortical thinning patient has primary hyperparathyroidism - clinical: bone pain, GI disturbance, psych symptoms, stones - bones, stones, groans, moans - path: increased renal tubular Ca+ reabs, increased renal production of 1,25 dihyxroxy vitD, increased bone resoprtion via osteoclst acivation, hypophastemia due to decreased phosphate reabs in PCT - leads to osteoporosis that affects cortical (compact bone) of appendicular skeleton (pectoral girdle, pelvic girdle, limbs), cortical thinning and subperiosteal erosions -> can progress to osteitis fibrosa cystica - granular decalcification of the skull (salt and pepper skull), osteolytic cysts and brown tumors - vs. osteophorosis of aging - affects trabecular bone not cortical A. disorganized lamellar bone indicates Paget disease where serum Ca+ and Phosphorous are normal B. osteoid matrix accumulation around trabeculae is seen in vit D deficiency -> histo there is excessive unmineralized osteoid with widened osteoid seams -> low urinary Ca c. osteopetrosis - perisstence of primary spongiosa in medullary cavit with no mature trabeculae. Caused by decreased osteoclastic bone resorption -> accumulation of woven bone and diffuse skeletal thickening d. postmenopausal osteoporosis - trabecular thinning with few interconnections

Tertiary and quarternary cholinesterase inhibitors:

Tertiary amines - lipohilic and cross BBB to reverse central and peripheral symptoms - physostigmine, galantamine, donepizil rivastigmine Quarternary amines - hydrophilic and do not cross BBB - neostigmine, edrophonium and pyridostigmine

312 35 yo woman G1P0 has abnormal quad screening results. Patient is at 18 weeks gestations. Drank wine in 1st tri bc didnt know she was pregnant. No meds. Immunizations UTD. AFP is low Unconjugated estriol is low B hcg is high Inhibin A is high What condition is causing analyte parttern/? a. fetal alcohol syndrome b. gastroschisis c. myelomeningocele d. omphalocele e. trisomy 21

Trisomy 21 Down syndrome: - most common chromosomal abnormality -associated with low AFP and unconjugated estriol on quad screen - correlates with decreased fetal levels due to suboptimal fetal tissue function + increased Bhcg and inhibin A due to compensatory placental hyperfunction - risk factors: AMA, parent with Robertsonian translocation - cause: usually meiotic nondisjunction especially failure of chromosome 21 to divide during meiosis - occurs during oogenesis and is associated with AMA, not in spermatogenesis - Robertsonian translocation: entire long arm of chromosome 21 is translocated to long arm of acrocentric chromosome (14) - one chromosome 14 is composed of long arms of both chromosomes 14 and 21 a. FAS - quad test not used to screen B. gastroschisis and omphalocele - increased AFP levels in maternal serum and amniotic fluid - High AFP is also associated with multiple gestation and open neural tube defects (myelomeningocele) - neural tube defects also assciated with increased Ach esterase

17236 58 yo man evaluated for thyroid nodule. Patient first noticed painless neck lump 2 months ago. Biopsy shows large number of follicular cells in clusters and microfollciles. Pt undergoes R thyroid o=lobectomy. WHich histo finding confirms diagnosisof follicular thyroid carcinoma? b. cells with empty appearing nuclei c. Hurthle cells d. lymphocytic germinal centers e. multinucleated giant cells f. tumor capsular invasion

Tumor capsular invasion Need to distinguish between follicular adenoma and carcinoma - carcinomas invade outside of tumor capsule while adenoms do not - done by histo exam of whole tumor, FNA cannot determine B. empty appearing nuclei - papillary thyroid carcinoma + laminar calcifications (psamomma bodies), ground glass cytoplasm, orphan annie eye nuclei, nuclear inclusion bodies and nuclear grooves - diagnosed by FNA c. Hurthle cells - polygonal cells with granular eosinophilic cyytoplasma due to many mt - seen in many thyroid lesions and neoplasms so cannot differentiated d. lymphocytic germinal centers - chronic autoimmune thyroiditis with signs of primary hypothyroidism + inflammation e. multinucleated giant cells in many thyroid conditions - thyroiditis, cystic degeneration, and papillary thyroid carcinoma - not in follicular lesions

1121: Insulin increases glycogen synthesis in hepatocytes. Activation of which mollecule promotes this effect? a.JAK c. phospholipaseC d. protein kinase A d. protein phosphatase

protein phosphatase Surface R for insulin is trasmembrane protein with intrinsic tyrosine kinase -> leads to phos. of insulin R substrate 1 (IRS1_ -> activates several intracellular pathways that induce physio effects of insulin Activation of MAP kinase pathway promotes mitogenic functions of DNA synthesis and clel growth Activation of PI3K stimualtes metabolic functions such as translocation of GLUT 5 to membrane, glycogen synthesis and fat synthesis -> glcycogen syntehsis by activating prottein phosphatase - deP glycogen synthase -> activation NOT protein kinase - intracellular effector enyzyme of Gs pathway -> which glucagon act s through to stimualte glycogen breakdon NOT phosphplipase C -> activated yby IP3/Ca second messenget system of Gq -> derades phospholipids into IP2 FA pg 85

14 mo boy as developmental delay and failrure to trive. Mother reports at 12 months he could barely lit head and has difficulty sitting unsupported. Toddler has not started babling. Low weight. Low gb, increased MCV low reticulocyte count and increreased ammonia. Urine contains large amunts of oroticc acid crystals. Supplementation with which substance would most likely benefit the patient? a. ascorbic acid b. folic acid c. guanine d. iron e. pyridoxine f. uridine

Uridine He has hereditary orotiic aciduria > AR -> de novo pyrimidine synthesis disorder that results i physical and metntal retardation, megaloblastic aemia, elevated urinary orotic acid levels. -> cause: defect in uridine 5' monophosphate synthase - polypep containisng 2 enzymatic domains that catalyze fibal conversion of orotic acid to UMP -> imapired conversion of orotic acid to UMP results in excretion of large orotic acid amounts in urie and clinical features described aove -> uridine sypplementation bypasses enzymatic defect and imrpvoes symptoms as uriend is converted to UMP via nucleoside kinase Increased urinary orotic acid is seen in ornightin transcarbamylase deficiency also but pts with this condition have failure to thrive and hyperammonemic encephalopathy within first few weeks of life

45 yo has progressively enlarging neck mass and hoarseness. Enlarged and nontender left thyroid lobe -> thyroidectomy. Fine needle aspiration biopsy is positive for papillary thyroid cancer and thyroidectomy is performed. On second postoperative day, patient develops tingling around mouth and muscle cramps in lower extremities. Light tapping anterior to ear elicits twitching of lower facial muscles. Increase in which of the following best explains this paitent's current symptoms? a. calcium binding by albumin b. urinary calcium excretion

Urinary calcium excretion Decreased calcium reabs by kidney secondary to acute hypoparathyroidism due to thyroidectomy -> also decreased 1 alpha hydroxylation of 25 hydroxy vit D -> decreased intestinal Ca abs (+ phosphate) -> decreased osteoclast activation -> decreased serum Ca+ Not calcium binding by albumin: Increased pH (alkalosis) > increases albumin binding to Ca+ => drop in serum Ca but this patient has no indications of respiratory or metabolic alkalosis

Inherited hypercalcemia. Borderline high PTH and very low urinary Ca and normal 25 hydroxyvitamin D. A mutation in which receptor is responsible for lab abormalities? a, membrane bound receptor coupled with G protein b. transmembrane ligant gated ion channel d. transmembrane receptor associated with intrinsic tyorsine kinase activity

a. membrane bound receptor coupled with a G protein Patient has decreased activity of Ca+ sensing Rs which downregulate PTH in response to high serum Ca+ -> they are transmembrane Gq protein coupled receptors that regulate the secretion of PTH in repsonse to changes in circulating calcium levels Familial hypocalciuric hypercalcemia -> -> AD > defective CASRs -> high serum calcium levels are required to suppress escretion of PTH -> increase set pint of Ca induced regulation of PTH secretions -> mild asymptomatic hypercalcemia, reduced urinary excretion of Ca and high normal or elevate PTH

848 Man has non healing ulcer on foot. PMH of diabetes with med noncompliance. BMI is 37. PE is significant for bilateral symmetric decrease in vibration sensation over feet and ankles. Which is associated? a. pancreatic islet infiltration with leukocytes b. pancreatic islet amyloid deposition d. strong linkage with HLA class 2 gene makeup

amyloid deposition Beta cell dysfunction due to islet amyloid polypeptide (amyloid) stored in secretory granules and is cosecreted with insulin from beta cells -> deposits in islets in patients with type 2 diabetes due to increased amylid/insulin secretion for compensation in early diabeetes D. Strong linkage with HLA class 2 gene makeup - strong association in type 1 diabetes - HLA-DR3 and HLA-DR4. Unknown genes involved in type 2 genetic components but type 2 > genetic association than type 1

What is the inheritance of PKU?

autosomal reccessive

279 Man has severmal months of choking spells, dysphagia and cough. Also has recurrent episodes of pneumonia. Other medical problems include HTn and osteoarthritis. BP is 130/70. Patient has foul smelling breath but oropharyngeal and neck exam are normal. Cardiopulm exam is normal. barium swallow study shows abnormality in upper esophagus. a. cricopharyneal motor dysfunction c. increased intraluminal pressure in stomach d. retetion cyst due to duct obstruction e. scarring and traction of esophagus

cricopharyngeal motor dysfunction Patient has Zenker diverticulum - path: abonormal spasm or diminished relaxation of cricopharyngeal muscules during swallowing -> early oropharyngeal dyspagia with food obstruction and lavel of neck and coughing/choking -> increased oropharyngeal intraluminal pressure eventually herniates pharyngeal mucosa through zone of muscle weakness (false diverticulum) in posterir hypopharynx (Killian triangle) -> food retention with halitosis and regurg -> pulm aspiration may lead to recurrent pneumonia -> may become palpable as neck mass lateral if enlarges and can worsen due to luminal narrowing by extrinsic esophageal compression Deglutition (swalloing) 1. voluntary oral phase: food bolus is collection and lifted upward to postioer wall of phrynx 2. initials pharyngeal phase: involuntary pharyngeal muscle contraction that propels food bolus to esophagus 3. esophageal phase: food stretches wealls stumulated peristalsis above site of distension. Relaxation of LES -> food enters stomach c. mallory weiss tear d. retention cysts form due to accumulation of trapped secretions following obstruction of gland duct -> chronic rhinosunusitis causes mucous retention cysts in maxillary sinus e. mediatinal lymphadenitis due to TB, funal infection, scarring/traction of esophagus -> true diverticula

1503 5 year history of lumbar pain and 2 year history of bilatral knee pain. Pain worst after long day on feet. Taken ibuprofen intermittently but pain is no longer tolerable. Patient has paternal aunt withh ostoarthritis. PE shows blue black spots on sclerae and diffuse darkening of auricular helices. Which is cause of patient's arthritis a.

homogentisic acid dioxygenase deficiency Pt has alkaptonuria ->deficiency in homogentiasate oxidase in pathway of tyrosine degradation to fumarate -> homogentisic acid sccumulates in tissues -> inheritance: AR -> prx: blue black connective tissue, ear cartilage, sclerae (ochronosis) + urine turns black on prolonged exposure to air + arthralgias due to homogentisic acid toxicity to cartilage

1984 Woman collapses due to hypoglyemia. Which is the best method of onrmalizing blood glucose? a. buccal glucose paste b. IM epi c. IM glucagon d. IN desmopressin e. sweetened fruit guice

in medical setting - IV glucose In nonmedical setting: glucagon Stimualtes hepatic glycogenolysis and gng -> return to consciousness within 10-15 minutes of admin If not availabel buccal or subligunal glucose or ucrose can be attempted but absorption is slow and sometimes ineffective b. IM epi does raise glucose but is less effective e. oral glucose is not recommended when unconscious due to risk for aspiration

1768 Rsearchers studying pathophys of DM identify family with inherited mutation in insulin gene. Results in single AA sub in proinsulin molecules. But sub is in segment of proinsulin removed during post translational processing of protein so family is asymptomatic. Polypep segment containing mutation is likely to undergo which process within pancreatic beta cells? a. degradation in lysosomes b. degradation in proteasomes c. degradation in RER d. direct translocation across PM e. storage in secretory granules

storage in secretory granules Insulin produced as preproinsulin -> N terminal signal sequence interacts with cytosolic signal recognition peptide which haltsprotein synthesis until ribosome translocates to RER -> translation resumes and peptide chain is extruded into RER -> N terminal signal peptide cleaved from preproinsulin to yield proinsulin -> conformational change and addition of 3 disulfide bonds in RER-> proinsulin to golgi where packed into secretory graules -> secretory granule endopeptidasees cleave proinsulin into inssulin and C peptide which are stored within granules until secreted via exocytosis