Uworld -sara- Random

What is the treament for BV?

alteration of normal vaginal flora assoicated with loss of lactobacilli and overgrowth of anerobes, gram variable rod gardernella vaginalis thin, gray, clear malodours vaginal dischage. more prominent on KOH Treat: Clindamyocin and metronidazole. Clindamycin is bacteriostatic - inhibit protein translation by binding 50s Metronidazole - bactericidal and damages teh DNA of anerobes, disulfram like reaction

70 yr old man with persisent aspiration, 2 week had a stroke affecting speech voice and swallowingm barium shuts aspiration of fluids without nasal regurg, ameliorated when patient flex his neck to put his chin to his chest during swallowing This augments what airway protective feature?

3 main airway protective movemnts: 1. displacement of larynx superiorly and anteriorly under the base of the tongue, which allow food to be directed into the most posterior located esopahgus 2. tilting of the epiglottis to the block the airway 3. closing of glottis by adduction of the vocal cords patient with stroke have persisent dysphagia or aspiration chin tuck maneuvar - flexion of head and neck during swallowing - dec distance from the hyoid bone to the larynx (stimulating evelation of the larynx) as well as narrow the distance of entrance, leading to dec aspiration

82 yr old man, behavioral changes, parannoid, talks out loud as if convo is with no one else, during recent argument, accused of being an imposter and steaing, is not clean, doesnt take after self, stopped watching baseball his fav hobby, cant live independent for 2yrs due to forgetfulnes and inability to perform self care, What is dx?

Alzheimer forgetfullness, functional impairment, followed by development of psychotic symptoms (delusions, hallucinations) -->AD most common dementia, insidous onset (>65) early impairment of recent memory, executive dysfunction, visuospatial deficits commonly complicated by development of neuropsychiatric sympoms, apathy, depression, hallucinations, disinhibition, agitation,

Antiiral activity of guanosine derivative, what explains variations in susceptibility of the various viruses to specific antiviral agent?

drug phosphorylation rate Drug works with HSV 1 and 2, and VZV but not CMV or EBV... acycolvir -- guanosine analog -- it is phosphorylated to acyclovir monophosphate, via a virally encoded thymidine kinase. rate limiting step of acycolvir activation then acyclovir monophosphate is phosphorylated by cellular enzymes into the active triphosphate form, which impairs viral DNA polymerase mediated replication of HSV mutations in viral DNA polymerase can lead to acycolovir resistance

58 yr old man with abrupt onset, severe cehst pain that radiate to back, bp is 220/130 in left arm and 180/100 in right HR is 100, name show normal serum troponin, ECH shows negative for ST changes. Triggered by what? dx?

Aortic dissextion - severe retrosternal chest pain radiating to the mid upper back that can move downward as the dissection progresses. initated by tear in aortic intima extending from 1-5 xm in transverse or oblique direction Type A - ascending aorta Type B - descending aorta the blood pressure descrepancy says brachiocephalic trunk servicing his right arm PRimary risk factor: hypertension see medial hypertrophy of aortic vasa vorum and reduced blow flow to aortic media... can lead to medial degeneration with loss of SM cells, leading to aortic enlargement and inc wall stiffness. the all stress and hypertension are synergistic

How do ANP and BNP work?

Atrial natruiretic peptide and Brain naturietic peptide and NO activate guanyl cyclase and increase conversion of guanosine 5 triphosphate to cyclic guanosine 3'5 monophophate (cGMP) Phosphodiesterase inhibitors (sildenafil) dec the degradation of cGMP. elevated intracellular cGMP levels lead to relaxation of vascular smooth muscle and vasodilation Penil erection if from release of ach and NO from parasympathetic fibers, leading to rise in cGMP and vasodilation of arteries uspplying the corpus cavernosum Sildenafil a phosphodiesterase 5 inhibit decrease the degradtion of cGMP if coadmin with nitroglycern or isosorbide mononitrate , can lead to excessive cGMp and severe hypotension

65-year-old man comes to the ER with fever chills and confusion history of poorly controlled diabetes a nonhealing ulcer on fire he has a fever low blood pressure and high pulse respiration or high he's slightly erythema surrounding his left foot ulcer with foul smelling discharge. But cultures or obtain and he started on broad-spectrum anabiotic's 24 hours later blood cultures grow beta-lactamase producing Bacteroides species what is the most likely to treat?

Bacteroides are gram-negative anaerobic rod that produce B-lactamase, enzyme that breaks down pencillin. B-lactamase inhibitors - tazobactam, calvulanic acid, sulbactam prevent enzymes from functioning. Combincation piperacillin and tazobactam is effective aganist a large number of gram positive, negative, anaerobic bacteria

22 yr old male in er with fever, abdominal pain and vomiting, for 4 days, no meds, right lower quadrant pain with rebound and a mass, ct shows periappendicular fluid accumulation What would be isolated from culture?

Bacteroides fragilis perforated appendixitis that evolved into intraabdominal abscess B. fragicilis - anaerobic gram negative bacillus. has surface polysaccharides that favor abscess formation intraabdominal infections can also be from E.coli, enterococcus, and streptococci

What is enteropeptidase responsible for?

duodenal brush border enzyme response for activation of trypsin from inactive, trypsinogen. once active, trypsin cleaves peptide bones in dietary protein and activate other pancreatic enzymes deficeicny of enteropeptidase --? protein and fat malabsorption as trypsin is required to activate lipid and protein digestion leads to diarrhea, failure to thrive and edema (due to hypoproteinemia)

How is isoniazid metabolized?

Bimodal (discont, polymorphic) cruve.. result in 2 distincy group with study populaton, one rapidly concert drug to metabolites and other more slowly Isoniazid is metabolized by acetylation to N-acetyl-isoniazid in hepatic microsomal system by enzyme N-acetyl transferase and excreted in urine. Slow acetylators metabolize low - dapsone, hydralize, and procainamide, with accumulation of drugs are at inc risk of toxicity, while fast require more drug to reach therapuetic dose

68 yr old woman burning sensation in her chest and throat for 2 weeks, trouble swalloing, has osteporosis, smoker, clear lung heart etc, symptoms due to meds, which when stopped her go away What drug? Ae?

Bisphosphonates - alendronate, risedronate Disruption of the protective phospholipid barrier in the lower esophagus. allows refluxing of gastric acid to cause mucosal erosion and ulceration. Contraindicated in esophogeal motility.- stricture, achlasia. should drink full glass of h20 and sit up for 30 min also cause osteonecrosis of the jaw (mandible or maxilla) and atypical bone fractures (stress fractures of subtrochanteric zone and femoral shaft) other meds: tetracyclines Asprin, NSAID potassium chloride, iron

10 yr old boy ER fell off bike etc, give lidocaine what is mOA?

Blockage of sodium channels. Local anesthetic that interrupts nerve fiber transmission by blocking sodium channels in the neuronal cell membrane, preventing depol of the nerve. Local anesthic have greater effect on small myelinated nerves, so they preferentially inhibit neurons that carry pain and temp sensation, pressure sensation and motor function are often preserved at typical doses. local anesthetics - weak bases that exist in charged and uncharged form, when uncharged form - diffuse thru cell membrane to block sodium channel from the inside of th cell. inc acidity in the surrouding tissue, which occur in infected wound, result in anesthetic molecules remaining in the charged form, rendering them unable to penetrate the cell mebrane to exert an effect.

46 yr old man with hiatal hernia nad gerd, undergoes antireflux surgery, endoscopic fundoplication is performed, the hiatal defect is repaired and gastric fundus is mobilized and wrapped around the LES to reinforce it. a neural structure transvering the esophagus hiatus of the diaphragm was inadvertently injured. What is the effect? what was damaged>

Branches of the vagus nerve (ant/post vagal trunks) pass thru the esophageal hiatus, can occur during fundoplication, may result in delayed gastric emptying and gastric hypochorhydria.

42 yr old woman with graves, hospitalized for elective total thyroidectomy, her hyperthrypid symp controlled with methimazole and propanolol, but still has goiter. take sout her thyroid, now has low ca levels, what med should u start?

Calcitirol parathyroid can be injuryed in thyroid surgery due to trauma, devascularization, or inadvertent removal... lead to transient hypoparathyroidism and hypocalemia can be asymp but develop paresthesia of lip, mouth, hand and feet, muscle twitching or cramps, can lead to tetany or trismus treat with oral calcium and Vit D. Calcitriol is active form of Vitamin D.

What does the splenic artery give rise to?

originate from celiac trunk and course superior pancreas give off: short gastric and left gastroepipolic artery immediately after passes teh greater curvature of the stomach. Short gastric have poor anastomoses, tissue vulnerable to ischmai from splenic artery blaockge but left gastroepipolic has strong anastamoses with right

64 yr old man dizziness, sob,for days, had lung cancer for last 6 month, pallative care, bp is 85/45 and opulse is 122 regular, resp are 22, pulse ox 94, has undulations in BP in different stages of respiration, PE , PMI is not palpable, heart sounds are distant. xray shows new enlargement of cardiac silhouette, What is expected of central venous pressure, RA cavity size, LA pressure, SV? Dx?

Cardiac tamponade from accumulation of fluid within relatively noncompliant pericardium, leading to an inc in pericardial pressure, the inc pressure compress the low pressure right sided heart and restrict diastolic filling of the right side of heart to cause obstructive shock becks triad.- hypotension, distant heart sounds, JVD , -- and also absent pmi and pulsus paradoxus (>12 mm hg in SBP with inspiration) the RA is dec in size, elevated RA pressure transmitted to vena cava -> inc central venous pressure, with dec right sided filling, less blood pumped thru pulmonary circulation to LA and lV --> dec SV and CO. although blood vol reaching LA is dec, LA P is inc due to compression by excess fluid. as progress, diastolic pressure in all 4 cardiac chambers (RA, RV, LA, LV) inc and equalize wtih pericardial pressure, eliminating normal pressure gradients and stagnating bf.

43 yr old man given amphotericin B due to aspergillous infection, he has decline in renal function, toxic effect is due to binding of antifungal to what?

Cell membrane cholesterol Febrile neutropehnia w/ chemo has invasive aspergillosis (fever, chest pain, hemoptysis, nodule with hypoattenuation consist with hal sign) amphotericin B is treament for systemic mycoses, it binds ergosterol of funal lead to cell lysis it is selective at higher affinity for ergosterol (in funal) than cholesterol in human but it does bind to some degree leading to AE 1. acute infustion related - fever, chill, rigor hypotenson 2. dose dependent nephrotoxicity - durg induced dec in gFR. perm loss of renal funciton due to cumulative dose, monitor creatinine. avoid with nephrotoxic drugs like aminoglycosides, cyclosporine 3. hypomag/hypokalemia 4. anemia - supression of EPO, can be severe if taking zidovudine 4. thrombophlebitis - site of injection

29 yr old woman with inc hair loss, delivery boy 8 month ago, not sam esince, fatigue, dec libido, period not returned, bp is 110/70, pulse is 58. PE shows diffuse apopecia, thick brittle nails, thyroid is nontender Lab show dec TSH and free thyroxine. What is teh diagnosis?

Central hypothyroidism low TSH confrms dur to a hypothalmis-pit dysunfciotn (central/sexondary) rathen than primary which would have high TSH. can also have low levels of gonatropic leading to amenorrhea sheehan syndrome - ischemic necrosis of pituitary gland and caused by systemic hypotension during delivrey, during preg- pit enlarge due to estrogren induced hyperplasia of lactotrophys, but blood supply doesnt inc proportionally subsequent hemorrahge with hypotension can cause underperfusion of pit gland with subsequent ischemic injury

25 yr old woman, 40 min after stung by several wasps, tightness and dizziness, bp is 80/40 pulse 120 and resp at 32. PE - diffuse erythematous plaques over the trunk and 1+ pitting edema of the ankles. What is cause of hypotension?

Chemical mediator- induced inc vascular permeability Anaphylaxis - type 1 immediate hypersensitivity. that occurs in response to an allergen (wasp venom) the initial exposure to an allergen results in antibody class switching and production of allergen specific igE by plasma cells. allergen specific igE binds to an igE receptor on mast or bas

what is an ecchymosis?

Cutaneous or subcutaneous collection of extravasated blood measuring at least 1 cm in diameter. can be superficial without history of noticeable trauma, but regularly indicate a deep hemorraage (hematoma) due to bony fracture, ligamentous rupture or muscular injury do NOT blanch cuz red cells r not in vasculature.

36 yr old from Peru, difficulty swallowing liquids, difficulty belching, eating slow and extending neck helps. no fever, weight loss, chest pain, cough, dyspnea or neuro symptoms. smoker for 18 yrs but no dugs , afrebrile, bmi 24, barium shows dilated esophagus, and manometry confirms absent peristalsis in smooth muscle portion of the esophagus. What infection? Dx?

Dysphagia and dilated esophagus -> achalasia -- absence of distal esophageal peristalsis and incomplete relaxation of hypertensive LES. is secondary to Chagas disease Chagas -- due to chronic infetion with Trypanosoma cruzi, a slender C or U shaped flagellated parasite with dark staining nucleus and kinetoplast. Parasitosis-related inflamation and immune mediated cross reactivity between parasite and enteric ganglia lead to submucosal (meissner) and myenteric (auerbach) plexus. uncoordinated SM act, inc tone and incomplete LES relaxation. mechanical dilation - due to obstructed liquids and solid -- proximal to functional obstruction manifest -- megaesophagus chagas can also cause nonischemic cardiomyopahy and megacolon Treat: bendozale or nefurtimox

24 yr old w bloody diarrhea, 10 day ago with episodic abdominal discomft and loose stools. progressively worsened and had 6-8 stools mixed with blood and mucus over past 2 days. Patient returned from 2 week trip to egypt and felt well Temp is 100.4, abdomen is soft with tenderness on lower quadrants no guarding, no bacteria, no c.diff but colonic ulcers with undermining edges that contain trophozoites. What else an this organism produce?

Entamoeba histolytica -- aomeba that effects GI transmitted fecal oral when cyst from contaiminated food or water common in poor countries most have no symptomns, but can have significant colitis with subacute bloody mucoid diarrhea, abdominal pain, and fever. Diagnosis: cyst and trophozoites on stool -- flask shaped colonic ulcers with trophozoites can spread to liver, lungs and brain hematogenously --> most common - single amebic liver abscess in right lobe. invasive strains have proteases that degrade host extracellular membrane and secretory igA all -- contact dependent cytotoxicity -- amebic lectin binds the host cell, introduce amebic porin into the host cell and cause cell lysis treat: metronidazole or paromomycin or iodoquinol for asymptomatic cyst passers trophozoites (with engulfed RBCs C in the cytoplasm) or cysts with up to 4 nuclei in stool D ; Entamoeba Eats Erythrocytes

researchers analyze the HIV viral structure and replication cycle for new drug target, find the virus endcodes a large glycoprotein that gets cleabed into 2 subunits , the sufrace and transmembrane. stay noncovalently bound to each other in the virion, upon activation of surface portein, conformational change occur in transmembrane exposing functional inner core. drug is developed that selectively bings and prevents normal functions of transmembrane subunit, interfeing with normal viral replication what does the drug inhibit?

Entry of the viral core into the host cytoplasm HIV gencome encodes for enezymes and structural protein sin polycistronic mRNA that are translated into polyproteins and cleaved by proteases into the individual proteins that compose the virus Env gene -- encde gp 160 -- extensively glycosylated in ER and golgoii and cleaved --? gp120 and gp41 gp120 and gp41 remain nonconvalent attachements and form the glycoprotein spikes that pepper the surface of virus gp120--> outer surface glycoprotein spike and mediated viral attachment to the host cell by binding with the CD4 receptor and chemokine coreceptor CXCR4 or CCR5. --binding o gp120 leads to conformational change that expose the gp41 transmembrane gp41 -- mediates fusion of viral cell membrane wit host cell membrane -- allowing viral core to enter the cell enfuvirtide (fusion inhibitor) bind gp41, prevent from undergoing conformational change for viral fusion that prevent HIV genome form entering the uninfected cells.

36 yr old woman with end stage renal disease, secondary to DM1, medical history hypertension, diabetic retinopathy, neuropathy, hemodialysis for 2 months with erythropoiesis stimulating agent, taking long and short insulin, lisinopril, calcitrol hemoglobin inc from 7.4 to 10 over 2 monhts what complication?

Erythropoiesis stimulating agents - erythropoietin, darbepoetin alpha - used to treat anemia of chronic kidney disease -- develop at gfr <30 untreated anemia in CKD and dialysis patients can lead to cardiac dysfunction, fatigue, wekaness and possible mental status change (dec cognition) but inc risk for thromboembolic events (vascular graft thrombosis, stoke) due to inc blood visocity, as elevation in red cell mass. many develop hypertension, due to action of erythropoietin receptors on vascular endothelial and smooth muscle cells

35 yr old prego at 38 weeks has gallstones, what is pathogenetic compoennt

Estrogen induced cholestrol hypersecretion and progesterone induced gallbladder hypomotility Estrogen inc cholestrerol syn by upregulating hepatic HMG-CoA reductase activity, which cause the bile to become supersaturated with cholesterol. progesterone reduces bile acid secretion slowing gallbladder emptying. when gallbladder is hypomotile, there is more cholesterol then bile salts and precipitate into insoluble crystals that eventually form gallstones.

65 yr old man for evaluation of blood in urine, no pain, urinary freq, or urgency. has htn, type 2 dm, stage 2 chronic kidney disease. quit smoking 10 yrs ago but did for 30yrs, bmi is 33. What is expected of abnormal kidney cells?

Gross painless hematuria of old person --> urinary tract cancer (urothelial or renal cell carcinoma). Rounded/polygonal cells with abundant clear cytoplasm --> clear cell carcinoma -- most common RCC. orginate from proximal tubular epithelial cells and has high intracellular glycogen and lipids. Tissue fixation and staining dissolve it showing clear spaces on pathological specimens.

What is does the CD 40 L do?

Expressed primarily on T cells, binds CD40 on APCs and B cells, lead to full activation (costimulation) so imp for cell mediated and humoral immune response APCs- binding to CD40L by CD40 on APC --> produce proinflammatory cytokines, express T cell costimulatory signals (CD80/86), inc phagocytosis, inc MHC class 2. this leads to activated of CD4 T lymphocytes -- for cell mediated response B cells - binding leads to formation of germinal centers somatic hypermutation (inc antigen-binding specificity) and immunoglobulin class switching (igG instead of igM) inc humoral response. since CD40L is need for class switching, mutations can lead to B cells overproducing igM --> hyper-igM syndrome... have both cell (prevention of PCP) and humoral (opsonization and destruction of encapsulated bacteria) immune response deficiency.

54 yr old man, episodic discomfort, nbloating, flatulence and occasional diarrhea. no blood in stool or weight loss, trying to avoid diary, didnt help, mild epigastric tenderness on deep palpation. stool occult blood testing is positive histo - hyperemic mucosa seen during Gi endoscopy reveal hyperplasia of branching, tubular submuscosal glands containing alkaline secretions. What area is biopsy?

First part of duodenum alkaline secretion from: 1.submucosal (brunner) glands secrete alkaline mucus into duodenum, most numerous in pylorus but can be found intermittently up the ampulla of vater. ducts of these glands pass thru the muscularis mucosa and terminate in mucosal crypts (crypts of lieberkuhn) 2. epithelial cells of pancreatic ductules and fucts -- watery secretions with high conc of bicarb, strong alkaline pancreatic secretion are then empetied into duoneum Tactile stimulation of duodenal muscoa and inc parasymp activity following meals induce bicarb secretion from submucosal glands. in addition, presence of acid in duoden and jejunum --> release of secretin from muscoa, stim secretion o fbicarb from submucosal glands and pancreas. H pylori can lead to hyperplasia of submucosal glands

16 yr old boy with mild intellecutal diability is evaluated for ADHD, he is impulsive and inattentive and teachers are cncerned abou tpoor grades, history of gross motor and speech delay which received physical and speech therapies PE - long and narrow face, prominent mandible nad large testes, hyperlaxity of his finger and thumb joints. Dx?

Fragile X syndrome most common inheritied and 2nd most common congenitial cause of intellectual disability X linked loss of function of mutation in Fragile x mental retardation (FMR1) on long arm of X chromosomes; hypermethylation of cytosine residues females have milder expression most apparent after pubety long, narrow face, prominent forehad and chin, large testes, hyperlaxity of joints in hands, developmental delay (speech and motor) in infancy, neuropsychiatric features (anxiety, adhd, autism ) can have self mutilation, nucleotide 3 peat CGG - Chin (protruding), giant gonads.

55 yr old man, was healthy, bad work performance, missing important deadline and mismange client account, became more irritatable during time and started to curse at cowrokers, mean to wife with no remorse, has a sweet tooth, eats 2 boxes of cookies a day. Dx?

Frontotemporal dementia (FTD) - early onset dementia prominent behavioral changes disinhibiton - socially inappropriate apathy/ loss of empathy -- loss of interest in activities and impaired socail relationships - verbal abuse hyperoralitiy -- change in diet, often with preference of sweets, more sever - bind eating or eat inedible objects compulsive - simple repetive speed or motions or complex - hoarding following new relgion degeneration of prefrontral cortex - include anterior temporal lobes, Aggregates of phosphorylated tau protein --tau assocated with neuronal microtubules and stablization. becomes hyperphosphorylated and disassociated from microtubules which lead to instability and disrupted axonal transport. aggregate to form inclusions that can appear like neurofibrillary tangles (similar to alzheimers) or round inclusions (pick bodies ) abnormal TDP-43 protein inclusions -- involved in DNA reapir and transcription, become ubiquitated in FTD.. also found in ALS.

29 yr old with intermittent nipple discharge for past several weeks, no fever or breat pain, never pregnant dispite unprotected sex, period at 12, 1 year ago period slowed to every 2-3 month and stopped 6 month ago, bmi is 31, PE - discharge is expressible from boht nipples b-hcg is neg What is dx?

Galactorrhea - abnormal sectreion of breat milk not associated with feeding or prego due to excess prolactin hyperprolactinemia - amenorrhea due to inhibitory effect of prolactin of GnRh Lactotroph adenomas (prolactinomas) - homornally active pit tumor and can cause very high prolactin levels. prolactin is under negative regulation by hypothalamic dopaminergic neurons via the pit stalk, and any disruption can moderate in men and post menopausal women -- dec libido (early symptoms) are mild and nonspecifc -- leater get headache and bitemporal hemianopsia ude to compression of optic chiasm in suprasellar region. give dopamine agonist.- bromocriptine and cabergoline

5 yr old boy , 2 days dark, low volume urine and decreased energy, parents say that boy had fever bloody diarrhea for 4 days that went away without treatment, PE shows pallor, swam in a lake and ate hamburgers, no peripheral edema or rashes, labs show anemia, thrombocytopenia and elevated BUN and creatinine. What dx? What would be seen?

Hemolytic uremic syndrome - SUG -- Shiga toxin producing E Coli O157:H7 or shigella dysenteriae shiga toxin enters circulation from the bowel and induces capillary endothelial damage, resulting in platlet activation with formation of microthrombi Platlet consumption causes thrombocytopenia where microthrombi lead to erythrocyte damage (forming shistocytes) and hemolytic anemai - pallor, weakness, tachycardia damage to glomerular endothelial cells cause acute kidney injury (oliguria/anuria, inc creatinine) HUS -- dec haptoglobin and hemoglobin and inc serum lactate dehydrogenase and unconjugated biliruibin. can see inc in bleeding time cuz of reduced platlets. not associated with clotting or DIC

41 yr old woman, menorrhagia, low hemoglobin, iron def anemia takes oral ferrous sulfate, after 3 months, labs better, wants to stop meds, cuz worried about iron buildup. What cell secrete a substance that controls iron storage and release by other cells invovled in iron hemostasis?

Hepcidin = acute phase reactant syn in liver that acts as central regulator for iron homeostasis. high iron levels and inflamm condition in syn of hepcidin, while hypoxia and inc EPO lower hepcidin. Hepcidin influence iron storage thru interaction with ferroprotin, transmembrane protein for transferring intracellular iron to circulation.. upon binding to hepcidin, ferroportin is internalized and degraded, dec intestinal iron absorption an dinhibit release of iron by macrophages. Regulation of intestinal iron absoprtion is crucial for maintaining iron homeostasis, since blood loss i sonly way to lose iron. iron absorption in proximal SI -- via DMT-1 (divalent metal transporter)-- once inside cells -- can bind to ferritin (primary intracellular iron binding protein) and remain stored in enterocyte. secreted in stool as enterocytes slough off 2. iron may enter circulation thru ferroportin, basolateral iron transporter on enterocyte, free iron released is transported throughout the body by transferrin (an iron binding transport protein) which becomes internalized after interacting with transferrin receptors on all cells

45 yr old man with involuntary movements and behavior change, frequent jerky irregular of upper extremities and worse over last month, genetic anaylsis shows mutation effect huntingtin protein that causes transcriptinal regression of a number of other genes. What mechanism responsible for gene silencing?

Huntingtin - AD neurodegenerative inc of CAG triNT repeat in gene that codes for huntingtin protiein expansion of protein polyglutamine region --> gain of function mitation leading pathological interaction with other proteins, inc transcription factors Transcriptional repression (silencing) -- mechanism by huntingtin is thought to cause disease. Regulation of transcription is due to presence of histones, small proteins that complex DNA to compact strands Acetylation of hisotnes --> weaken DNA histone bone and make DNA segments more accessible for transcription gactors and RNA pol, enhancing gene transcription in huntingtin, abnormal huntingtin can cause increased deacetylation... silencing the genes necessary for neuronal survival.

35 yr old man with exertional dyspena and dry cough for 8 months, oxygen sat on room air is 96 layin down and 88 6 min into walking, fine crackles in both lungs, xray shows reticular densities in both lung fields, infiltration of inflammatory cells, predominately lymphocytes, and poorly formed noncaseating granulomas and moderate alveolar septal fibrosis. What is dx?

Hypersensitivity pneuomonitis chronic dyspnea nad cough, exaggerated immunologic response to an inhaled antigen, common = mold, bacteria, animal prtein, chemicals acute - abrupt onset, recurring episodes - fever, chills cough dyspnea and fatigue with intermittent high dose exposure. Leukocytosis is prsent , x ray can be normal or show scatter micronodular opacification chronic - persistnet and gradually progressive -long term moderate dose antigen eposure, couhg dyspnea fatigue and weight loss for months, lungs show fine crackles and xray shows interstitial reticular opacities consisent with pulmonary fibrosis function testin - restrictive pattern have low DLCO and hypoexemia lymphocytic infiltratie with poorly forming noncaeasting granulomas created by walling off inhaled antigens. chronic - progressie alveolar septal fibrosis

What are the AE of isoniazid?

INH - injury to neurons and hepatocytes. acute mild hepatic dysfunction due to transient inc in AST/ALT, usually during first 4-6 months of treatment can lead to frank hepatitis similar to viral with a fever, anorexia, nausea, and jaundice adn can occur and rvolve into severe liver dysfunction and death.

31 yr old transient visual changes -- loss of vision for a min, precipiated by bending forward or lifting objects, for 3 months has headaches, over the counter meds dont help, bp is 140/90 and pulse is 72. BMI is 32 What is the cause?

Idiopathic intracranial hypertension (pseudotumor cerebri). presents in obese young women with daily headache, bilateral systemic papilledmea, and transient visual distrubances related to impaired cerberal venous outflow and inc intracranial pressure worsening valsalva maneuver - bending, couhgin, cuz intracranial pressure inc. inc intracranial pressure if transmitted thru the csf in the subarachnoid space, which is continous with optic nerve sheath, build of pressure compresses the optic nerves externally, which in imturn impairs axoplasmic flow within optic nerve causing bilateral optic disc edeam fundoscopy shows == optic disc with blurred disc margins.

64 yr old man with worsening back pain fatigue and polyuria, PE shows mucosal pallow and diffuse bony tenderness, labs show normocytic anemia and hypercalecemia and renal failure, monoclonal spike in gamma globulin region, large number of abnormal plasma cells. treatmetn with lenalidomide, inc affinity for E3 ubiquitin ligase enzyme to substrate transcription factors. What is the effect of meds on transcription factors?

Inc intracellular degradation Multiple myeloma - plasma cell neoplasm with overproduction of monoclonal immunoglobulins. proliferation of neoplastic plasma cells in BM cause bone pain (back pain) , hypercalecemia (polyuria) and osteolytic lesions... also get normocytic anemia and renal insufficiency mediations that inhibit proteasome activity (bortezomib) or inc ubiquitination of reg proteins produced in excess in neoplastic cells (lenalidomide) Lenalidomide - derivative of thaidomide - an antiemeit cused for prego but teratogenic inc affinity for E3 ubiquitin ligase to transcription factors (ikaros and aiolos 2 zinc fingers ) that are overexpressed in myeloma cells. -- leads to distruction by proteasome. TF are needed for myeloma survival so cause cell death can also be used for mantle cell and myelodyplastic syndrome Bortezomib, ixazomib, carfilzomib Proteasome (induce arrest at G2-M phaseapoptosis) Multiple myeloma, mantle cell lymphoma AE: Peripheral neuropathy, herpes zoster reactivation

Sildenafil AE?

Inhibit PDE5 to get boner but can also inhibit PDE6 in the retina, involved in color vision, experience bluish discoloration to vision, less common include nonarteritic anterior ischemic optic neuropathy -- sudden monocular vision loss associated with an afferent pupillary defect, dec visual acuity and optic disc edema.

4 yr old boy, difficulty breathing, productie cough, pmh with recurrent sinusitis and otitis media, resp infections have a protracted course, but respnd to high dose antibiotic therapy, crackle and wheeing, CE - PMI is on right 5th intercostal space. What is the dysfunction? dx?

Kartagener syndrome - primary ciliary dyskinesia... AR -- mutaitons that impair structure or function of cilia Eukaryotic flagella nad cilia -- central core - axoneme - surrounded by 2 central microtubules (9+2) arrangement, axoneme is achnored to the cell by a basal body. Each doublet has an A and B subunit and is connected to adjacent doublet via dynein arms. Dynein arms contain ATPase that generates energy to slide teh microtubules past each other, producing ciliary movement. Primary ciliary dyskinesia - can be from failure of dynein arms to develop. get reccurent resp infections (chronic sinusitis, bronchiectasis - impaired mucocilary clearnace), during embryogenesis can cause situs inversus, infertility in men (impaired sperm mvement) and women (immobility of fallopian tube cilia) test- decreased nasal NO

What do u use to analyze 2 independent varibales?

Linear regression regression analysis - association between 1 or more independent variables (exposures, risk factosr ) which can be quantitative or qualitative and 1 quantitive outcome.

62 yr oldman with chest pain and palpitations, CAD, ischemic cardiomyopathy, paroxysmal afib, hypertension, BO is 135/78, pulse 78, 2 brief loss of consciousness, ECG shows polymorphic QRS complex that change in amplitude and cycle length. between episodes, QT interval prolongation but otherwise remarkable What meds? dx?

Long QT syndrome with torsades de pointes Torsades - polymorphic ventricular tachycardia characterized by QRS complexes of varying amplitude and cycle length giving appearance that tip of the QRS is "twisting" around ECG baseline. is always associated with long qt interval. can terminate spontaneously --> degenerate into vfib and sudden cardiac death Aqcuired QT prolongation is most frequent caused by -- hypokalemia, hypomagnesemia -- and class 1A and 3 antiarythmics (quinidine, sotalol), antibiotics (macrolides, fluroquinolines), methadone, antipsychotics (haloperidol) Sotalol - class 3, K blocking agent used for afib.

1 week old newborn with abnromal thyroid fxn, low serum T4 and normal serum TSH, later... Free T4 normal and total T4 lnormal and TSH nromal dx?

Low total T4 but normal free T4 and normal TSH is deficiency of thyroxine binding globulin (TBG), benign, x linked. majority of T4 is bound to TBG, which then serves as a storage pool to replenish active free T4 which is cont cleared by kidney, normally euthrypid, asymptomatic

19 yr old man, needs glasses for myopia, patient is tall with long upper extremities and fingers, face is narrow with down slanted palpebral fissures, flattened malar bones, and small jaw. late systolic murmur at the cardiac apex. What is cause?Dx

Marfan syndrome -- AD - FBN1- fibrillin 1- component of extracellular matrix microfibrils. Provide support to elastic fibers nad maintain CT integrity. regulats ECM remodelling by binding and sequestering TGF-B in marfan - cant find TGF-b leading overexpression of free TGF-B leading to inc prodution of MMPs, which cleave elastic fibers and reduce tissue integrity. leading to fragmentation of elastic fibers and dec collagen density with pooling of gags (myxomatous mitral degeneration) -- prolapse into atrium -- midsystolic click on ausculation and mitral valve regurg mid to late systolic apical murmur if serve can lead to holosytolic.

35 yr old woman, prego at 18 weeks has amniocentesis showing inc level of acetylcholinesterase. Most likely suggest failure of what?

NTD- neural tube defects occur due to failure of the neural plate edges during 4th week of fetal development. Fusion begin in cervical region and proceed toward the cranial and caudal ends of the neural tube (rostral and and caudal neuropores). Failure of rostral neuropore to close results in anencephaly, where impaired closure of caudal neuropore -- > spina bifida . if neither close --> opening between neural tube and amniotic cavity --> AFP and Acetylcholinesterase leak into amniontic fluid. AFP and ACHe used for prenatal screening of NTDs (spina bifida cystica and anecephaly).

What is perfusion limited vs diffusion limited?

Normal oxygen transfer is perfusion limited as in diffusion is so fast that oxygen transfer depends on the perfusion rate (CO) only. Diffusion limitation - hypoxia that occurs in disease that disrupte the alveolar capillary membrane (empheysema, pulmonary fibrosis).. progressive dyspnes and fine inspiratory crackles - interstilial lung disase.. fibrotic thickening of the interstitial space between air and bloow, inc the distance that oxygen has to cross .. limiting the degree of oxygen diffusion during exercise, there is inc pulmonary blood flow, accelerates transit thru the pulmonary capillaries, reducing the time for oxygen extraction. in patients with diffusion limitation, the inc blood flow during exercise can result in exertional hypoxemia, if oxygenation is normal at rest.

How does obesity effect lung volunes>

Obesity, particularly morbid, central obesity, can cause a pattern of extrinsic restrictive pulmonary function tests. The most common indicator of obestity related is reduction in ERV and FRC but fev1, fvc, and tlc are also normally decreased.

52 yr old with chronic cough, with phelgm and blood, smoked 2 pack cig a day for 30 years, drink 3/4 beers, welder on assembly line, father deid at 70 of lung cancer, PE = right sided face and arm swelling and engorgement of subcut veins on same side of neck, What vein is most like obstructed?

Obstructed right brachiocephalic (innominate) vein. may be due to compression of apical lung tumor or thrombotic ocxulusion due to central catheter. Brachiocephalic formed from union of right subcalvian vein and right internal jugular vein. The right external jugular vein drains into the right subclavian, so obstruction of the right brachiocephalic can also cause venous congestion of structures drained by external jugular vein. right brachiocephalic also drain into right lymphatic, which drain lymph from right upper extremity, face, neck, right hemithroax, RUQ abdomin

a unvaccinated 20 month old girl, with rash, 3 days ago had a fever with cough, congestion, and red eyes, rach appeared on her face yesterday adn spread to trunk, arms and legs, temp is 103, lethargic, ill appearing, PE shows conjuctival injection and diffuse, maculopapular, erythematous rash, Def of what is associated with high rate of complications? Dx?

Patient has Measles- high contangious paramyxovirus that spread cua contact or aerosolized resp droplets, Exanthema - starts on face and spread to cephalocaudal and cetrifugal pattern, Erythematous, blanching, maculopapular lesion s- deep red, nonblanch and coalesced rash Vitamin A supplemntation - suggested esp with def, acute measles depletes Vit A stores resulting in risk of keratitis and corneal ulceration. Vita A prevent and treat oclar complications, red risk of comorbitiies, recovery time and hospital stay.

55 yr old man with sob, productive cough and confusion. had flu and symptoms have gotten worse, temp is 103, bp 80/50 and pulse 120, resp 22. intubaed, 2L bolus of normal saline and started on broad spectrum ab, central line is placed to access a structure embryonically derived from the common cardinal veins. What structure?

Patients with hemodynamic instability or shock have central lines places: neck - internal jugular vein or chest - subclavian vein and advanced until the catheter tip hits the SVC. SVC is derived from common cardinal veins. SVC is right of the heart, posteriolateral to the ascending aorta, anterior to the right pulmonary artery and jue below the level of carina. umbilican vein degenerate vitelline vein form the portal system and cardinal vein form SVC

34 yr old man with upper adomnial pain, vague discomfort in the afternoon and night, partially relived by food, feels nausea, no vomiting, black or bloody stools, weight loss. small ulcer with clean base at duodenal bulb. Where is the infection?

Peptic ulcer - due to H pylori or nsaids H pylori colonize the gastric antrum in early disease associated with dec somatostain and inc gastrin secretion, stimulate the parietal cells to produce excess acid. result in inc acid load emptying into proximal duodenum including duodenal ulcer formation Gastric ulcers - colonization of gastric corpus (body) -- not acid related - more direct mucosal damage and chronic inflammatin, GU pain often worsen with eating,

29 yr old women, persistent fatigue ober last 4 years, unhappy ever since let go from previous job, has "little energy to do things", everything in life is a chore and hopeless that it will improve. no suicide, prob conc, or change in appetite or sleeping, used weed as a teen and drink 1-2 glasses of wine on weekends. dx?

Persisent depressive disorder (dysthymia) chronic depressed mood for >=2 yrs or 1 year in children/adolescents. more days than not. Presence of 2 or more symptoms never meets criteria for major depressive episode

What medication causes gingival hyperplasia?

Phenytoin -- can be reversible with withdrawal 50% of ppl with 3/4 months of phenytoin therapy. due to inc. Platlet derived growth factor (PDGF) when gingival macrophages exposed to inc amount of PDGF, they stimulate proliferation of gingival cells and alevolar bone Phenytoin - anticonvulsant - grand mal (tonic-clonic), partial and status epilepticus Inhibits abnromal electrical activity of brain by blocking voltage gated sodium channels in the neurons. has narrow theurapetic window: - mainly CNS, cerebellum and vestibular system -> ataxia, nystagmus -gingival hyperplasia, coarsening of facial features, hirutism - metabolism of folic acid and --> megaloblastic anemia -induce CYP450 - inc metabolsim, dec conc of blood level of meds - during pregnancy - phenyptin can cause fetal hydantoin syndrome

38 yr old woman, 35 weeks gestation, sudden onset visual changes and headache, reports spots in her vision for hte past few hours and occipital headache, took a dose of acetaminophen but no improvement bp is 168/114 and pulse is 90. pulse are equal and reactive to light, extraocular movements are intact, partial loss of vision bilaterally What caused ?

Preclampsia = new onset hypertesnion (systolic >= 140 or diastolic >= 90 ) at >= 20 weeks gestation with proteinuria and signs of end organ dysgunction triggers widespread endothelial dysfunction -- dysregulated vascular tone (vasopasm, vasoconstriction), inc vascular permeability and dec end organ perfusion headache - serve and throbbing, can be due to dysregulated cerebral blood flow, brain ischemia, cap leakage -- cerebral edema visual changes or photopsia (seeking sparks) and scotomata (partial vision loss blind spots) are due to retinal artery vasospam and optic nerve ischemia eye movement and pup light reflex is intanct

26 yr old owman, worsening genealized weakness, myalgias, unintentional weight loss. has primary hypothyroidism takes levothyroxine. BP is 110/70 supine and 90/60 standing. she is emaciated. Labs show mild normochromic, normocytic anemia, eosinophil count is 15% and serum glucose is 65. What changes are expected in serum Na/K and urine? dx?

Primary adrenal insufficiency - aka Addison result from autoimmune destruction of bilateral adrenal cortex -- occurs often if people have other autoimmune disease (Dm1 or hypothyroidism) Reduced aldosterone leads to salt wasting with consequent hypovolemia and orthostasis ( sbp >/= 20 with standing) reduced cortisol --> hypoglycemia, normocytic anemia and eosinophilia. in Collecting tubule principal cells -- red. aldosterone leads to dec na and inc K absorption.. so high urine Na , low K serum K is high due to inc absorption. tubular salt wating reducing total body sodium but doesnt directly effect serum Na con, but hypovolemia leads to ADH which is normally inhibiting by cortisol, so ADH levels are inc. this can lead to inc water absorption and low serum na - hyponatremia

HOw does taking 10 days of oral medroxyprogesterone lead to moderately heavy bleeding with some cramping, what cellular process caused the bleeding?

Progesterone is typically secreted in luteal phase and stimulated endometrium to transform from proliferative to secretory and become a goo dplace for implanation.. Endometrial glands become more elaborate and spinal arteries coil Exogenous intake of progesterone for 20 days matures the endometrial lining When the endometrium is no longer exposed to progesterone (progesterone withdrawal) prostaglandins production inc, leading to vasoconstrition of spiral arteries, cause inc secretion of MMPs by endometrial stromal cells (elading to degradation of ecm) and apoptosis of endometrial epithelum net effect -- degeneration of functionalis layer, which slough away as menstrual flow

68 yr old woman with inc low back pain, constant worse at night, weight loss for. 3month, osteoporsis and hypothyrpidism, smoked for 30 years, drink 1/2 wine per day, immigrant from china, eats home cooked foods, Pe shows point tenderness at L3/L4, MRI shows lytic bone lesions in vertebrae and right lower ple kidney mass .. Dx? Risk?

Renal cell carcinoma -- back pain, osteolytic bone lesions, histo - rounded polygonal clear cell with metastic renal cell carcinoma norm asymptomatic until advanced, symptoms - hematuria, abdominal mass, flank pain, trial is <10% -- fever, weight loss fatigue and metastases to bone is common. Smoking - toxin exposure (trichloroethylene, asbestos, petroleum by products), obesity and htn and herediatry disorder (von hippel-lindau syndrome) Associated with paraneoplastic syndromes,eg, PTHrP, Ectopic EPO, ACTH, Renin ("PEAR"-aneoplastic).

50 yr old woman mild myopia for decade to office routine physical exam, patient has no chronic medical conditions and eat healthy, doesnt havent to wear glasses or contacts anymore, her visual acuity at 20 ft 20/30 in both eyes without wearing her glasses. what condition is same etiology?

Skin wrinkles Presbyopia and skin wrinkles are age related changes, Presbyopia occurs due to denaturation of structural proteins within the lens, leading to loss of lens elasticity which can result in improved vision in patients with mild myopia. dec syntheisis and inc breakdown of collagen and elastin contribute to the development of skin wrinkles. in accomodatopn - wehn focusing on near objects (reading), cilary muscle contraction relaxes teh zonular fibers, allowing the lens to become more convex so the image focuses on the retina at 40-50, cant focus on near objects, presbyopia - progressive denaturation of lens proteins and changes in lens curvature cause the elns to become less elastic and lose its accomodating power, this causes the image to be behind the retine, resulting in difficulty reading fine print and need to hold objects farther away in order to seem them clearly. with mild myopia - inc axial length with an image in front of retina, presbyopia can compensate for myopia by displacing the image backward, so it focues on the retina. so can see improvement in visual acuity with age as presbyopia develops.

T cell maturation positive and negative selection

T - lymphocytes are produced in bone marrow and migrate to mature in first semester of gestation in the thymus T cell receptor gene arrangement, +/- selection, expression of extracellular membrane markers and co stim molecules occur Pro-T cells arrive as "double negative" - no Cd4/8 antigens and begin differenitation in subcapsular zone next, TCR beta gene rearragenment occurs with simulataenous expression of both CD8 and CD4 Once in cortex, alpha gene rearrange and produce a function alpha-beta TCR; then +/- selection -- if fail -- apoptosis Positive selection: T cells expressing TCR that is able to bind self MHC are allowed to survive. in thymic cortex and involves interaction of T cell with thymic cortical epithelial cells expressing self MHC Negative selection: after Postivive, if T cells pocessing TCR that bind with high affinity to self antigen or self MHC class 1 or 2 are eliminated. occurs in thymic medulla and involves interaction of developign T cells with thymic medullary epithelial cells and dendritic cells. this eliminates T cells that are over reactive to self and can be autoimmune disorders.

55 yr old man with HIV, 3 week of inc headache, fever, vomiting, low bp and neck stiffness, he quickly deteriorates, and dies. autopsy - diffuse gelatinous exudate covering the base of the brain, cut sections show ventriculomegaly and frontal lobe infarcts but not intraparenchymal mass lesions. What is Dx

TB meningitis, most common CNS manifestation of disseminated TB. arise when circulating bacilli lodge in the subependymal or subpial space, forming a tubercle that ruptures into subarachnoid space. Findings: - thick, gelatnious exudate prominent in basal portion of brain, can encase CN--> CN palsy, invade circle of willis --> stroke - TB vasculitis of cerebral arterties --> multiple brain infarctions, in periventricular areas -hydrocephalus -> obstruction of CSF outflow by TB proteins, can cause inc ICP, and ventriculomegaly

What feature is the worst prognosis for colon cancer?

The extent of tumor expansion: Stage of the tumor Degree of tumor differentiation -- from well to anaplastic : grade Tumor STAGE is most important for prognosis if stage A: confined to mucosa, Stage C is lymph node and stage D is distant metastasis

23 yr old with acute attack optic neuritis, relapse remitting MS, demylination of the right optic nerve waht is expected of light reflex and pupil constriction?

Unilateral optic neuritis is most likely to demonstarte an afferent pupillary defect due to demyelination of right option nerve optic nerve carries the afferent limb of pupillary light reflex, tranmitting info about light to pretectal area in midbrain pretecta area activates the edinger-westhal nuclei bilateall which sen dparasymp efferent down CN3 to innervate pupillar sphincter muscle of the iris. cross over allows light entering one eye to cause both direct pupillary constriction in the ipsilateral eye and consensual pupillary constriction in contralateral eye. Optic neuritis and retinal detachment -- is afferent pupillary defect.

73 year old man, blood in urine, bright red blood at the end of micturition , no freq or pain with urination. smoked ofr 30 years, hematuria, urine cytology is positive for maligant cells. What feature is worst for progrosis?

Urothelial (transitional cell) carcinoma, most common bladder cancer. most important factor for prognosis based on depth on invasion into bladder wall and the degree of regional (lymph node) and metastic spread Tumor invasion into muscularis propria layer of bladder

53 yr old man with fever and progressive weakness over last 2 weeks, sob, from europe, diagnosed with heart disease, on autospy heart is large, friable masses on mitral valve with extensive destruction of cuspal tissue. what is predisposing?

Valvular inflmmation and scarring fever, progressive weakness, dyspnea (valvular regur) along with vegetations on mitral value -- infective endocarditis -- predisposing factoring are valvular abnormalites (rheumatic heart disease, mitral vale prolapse, prosthetic vavlues, congential heart disase) and conditions that promote bacteremia/fungemia (IV drug use, dental procedures) patient has rheumatic hear disease (immigrant from developing country) with underlying degneration of mitral valveu due to chronic valvular inflammation and scaring see adherence of fibrin and platlets - forming sterile fibrin platlet nidus.

43 yr old man retrosternal chest pain w/ moderate exertional and sometime at rest, no socail history, temp is fine, bp fine, pulse fine, coronary angiography shows mild luminal irregularities but no siginficant obstruction. Acetylcholine infusion results in dilation of epicardial coronary vessels a reaction with what AA is responsible for the dilation?

Vascular endothelium plays an important role in vasodilation mediated by Ach, bradykinin, serotonin, substance P and shear forces stimuli activate membrane receptors on endothelial cells, leading to inc in cytosolic ca levels. this causes activation of endothelial nitric oxide synthase (eNOS) which synthesises NO from arginine, nadph and o2. NO then diffused to adjacent SM, where guanylyl cycle is acticatd and inc formation of cGAMP high cGMP activate protein kinase G --> reduction in cytosolic Ca and relaxation of vascular SM cells availability of arginine is dependent on exogenous food intake, endogeneous ysn, intracellular storage and degradation and presnce of asymmetrical dimethylarginine (endogenous analog of arginine that works as a comp inhibitor of eNOS) can help iwht stable angina

78 yr old women with tenderness, easy bleeding of gums when brushin teeth, swollen gingiva that bleed on probing, coiled hair, hypoactivity of enzyme found where? Dx?

Vit C def - Scurvy - malnourished, alcoholics, poor elderly gingival bleeding./sweelling, petechaie, ecchymoses, poor wound healing, perifollucular hemorrhages and coiled (corkscrew) hairs Collagen synethsis - begisn with transcription of genes in nucleus. collagen alpha chains are synthesized in RER bound ribosomes and directed into cisternae RER - within RER , proline and lyine are post translationaly hydroxylated to hydroxyproline/lysine requiring vit X as a cofactor for post translational modifiation After formation of triple helix, procollagen are secreted from the cell via the golgi apparatus, N / C propeptides are cleaved by extracellular procollagen peptidase to form insoluble tropocollagen - monomers self assemnle into collagen fibrils that subsequently crosslinked via lysyl oxidase. hydroxylation leads to max tensile strength - occurs in RER

Patient is nasues after chemo treatment, where in brain responsible fo rthis?

acute vomiting after treatment, vomiting reldex is in chemoreceptor trigger zone (area postrema) and nucleus tractus solitarius. area postrema - dorsal surface of the medulla at the caudal end of the 4th ventricle, does not have a well developed BBB and is exposed to chemicals in blood the CTZ - can be trigged by drug or toxin or by vagal affarents from the Gi Chemo (cyclophosphammide) cause damage to erythrocytes, resulting in release of serotonin.. this stimulates 5-HT3 receptors on vagal afferent fibers located in bowel wall which ascend to teh CTZ to trigger vomiting reflex. chemo emetic stimulin csf and blood can stimulate area postrema by causing local release of substance P, which activated neurokinin-1 (NK1) in brainstem -> vomiting 5-ht3 antagonist - ondansetron and NK 1 receptor antagonists (aprepitant, fosaprepitant) can be used for ameliorate chemo induced nausea

4 week old persisent vomiting, fussiness, feeling intolerance, emesis was clear now is bilious in last few hours. infact has been breast feeding exclusively. temp is 99, bp and pusle nromal, PE shows normal abdomen with no rebound or guarding GE shows normal rotation but constriction of duodenum, CT - pancreatic tissue encircling the duodenum. What is the cause?

annular pancreas - abnormal migration of the ventral pancreatic bud. bud is foregut that appears in 5th week of gestation and rotate behind the duodenum during the 7th week of fetal development. ventral moves toward the mdiline, fusing with dorsal bud during 8th week. Ventral - give rise to uncinate process - portionof the head and main pancreatic duct (of wirsung). dorsal - tail, body, and remainder of head. Annular pancreas - rare congenitial in which pancreatic tissue completely surround the second part of duodenum. can compress teh lumen causing obstruction or result in obstructed pancreatic drainage (acute/chronic pancreatitis)-- most people are asymptomatic

what is the normal effect of aging on kidneys?

around 30, with more marked decline around 50, so elderly get acute kidney injury or chronic kidney disease - reduced renal mass and functional glomeruili - 50% reduction in functional glomeruli by age 75 associated with a reduction in renal mass due to atrophy and fibrotic replacement, red GFR and creatinine clearance, as well as reduced ability to concentrate urine, which may predispose to hypovolemia in times of stress reduced RBF - loss of renal vasculature results in reduction in renal blood flow with age, inc ishchemic injury become more dependent of prostaglandins to maintain adequate blood flow, leading to inc susepctibility to renal injury with NSAIDs reduced hormal responsiveness - reduced secretion of renin (blunt RAAS) and reducted hydroxylation of vitamind D in response to PRH but production of epi in response to anemia or hypoexemia is unchanged.

primary biliary sclerosis

autoimmune liver disease, destruction of small and midsized intrahepatic bile ducts with cholestasis, middle ageed women, associated with sjorgen and RA, fatigue, itching, hepatomeglay, inc LAP and + antimitochondrial ab titers bipsy - patchy lymphocytic inflammation leading to granulomatous destruction of intrahepatic bile ducts (florid duct lesion) with necrosis and micronodular regeneration of periportal tissues graft vs host disease - immune mediated destruction of intrahepatic bile ducts.. in immunocompromised following transplant of allogeneic bm or other lymphocytic rish tissue (nonirradiated blood). donor T cells migrate into host tissues, where they recognize MHC antigens are foren liver shows lymphocytic infiltrate and destruction of small intrahepatic bile ducts -- both are immunological disease

What is the greatest risk for HPV?

barrier contraceptives. carcinogenic strains of HPV (16,18,31) risk for squamous cell carcinoma of the cervix arise from squamocolumnar junction of the endocervix. starts with cervical intraepithelial neoplasia (CIN) in carcinoma in situ and proceeds to squamous cell carcinoma. CIN is usually transient in young healthy women. HPV 6 and 11, cause condylomata acuminata (genital wards) and have low maligancy potential high risk 16,18,21 integrated into human genome, leading to overexpression of viral oncogenes E6 and E7 E6 binds proteins p53 and increases its degradatio, where E7 bind to RB1 and displace transcription factors normally bound to pRB and the tumor supressor protein product of RB

Right gatric?

blood to less curvature of stomach, from proper hepatic

What does gastrodudodenal supply

blood to pylorus and proximal duodenum. from common hepatic

65 yr old man with lightheadness while buttoning tight shirt collor, 2 episodes when he passed out, bp is 70/40 and pulse is 45 during one episode. PMH for htn and DM, no smoker, PE - bp 135/72, pulse 76 without orthostatic changes, Stimulation of afferent sensory fibers in what nerve is responsible?

carotid sinus hypersensitivity - triggered by pressure on carotid sinus by tight shirt collar, carotid sinus baroreceptors are important in bp control and use arterial wall stretch as indicator carotid sinus is a dilation of internal carotid artery - above bifurcation of common carotid... Afferent limb -- from baroreceptor to medullary center via hering nerve- branch of Cn 9 - glossopharyngeal. efferent - parasymp impulses via CN 10 - vagus. carotid pressure or massage - stimulate barorecptors and inc firing rate of sinus , leading to inc of parasym output and withdrawl of symp out to heart and peripheral vasculature... get dec bp (peripheral vasodilation_ and dec CO (dec contractility/SV and HR). if sensitive peeps - bradycardia, hypotensin and syncope.

what is FISH used for?

cytogenetic test that can identify the presence of chromosomal duplications and large deletions or translocations probes are ssDNA segments that are a few hundred kilobases in length, added to cell of interest and anneal to complementary regions of the cell chromosome, more sensitive than traditional karotyping (chromosome banding) and can be applied to both metaphase and nondividing (interphase) cells used for 9:22 in CML and chromosomal inversions ownt be detected -- is only the presence of absense not order in which it is coded. highly sensitive and specific can be used on tissues with low mitotic rates.

31 yr old man, week of fever, night sweats, sore throat, maliase, and extreme fatgiue, multiple sexual partnerys, inconsistent condom use, temp is 100.4, bp 110/80, pulse 92, PE shows multiple shallow uclers on orpharyngeal mucosa, tonsils are enlarge and hyperemic, cervical and axillary lymphadenopathy is present, generalized, erythematous and maculopapular skin rish HIV testing show - negative ANTI-hiv ab, postiive hIV p24 and plasma hiv rna detectable what exaplains results?

early viral infection before serological response most patients with HIV develop mononucleosis-like symptoms (fever, diffuse lymphadenopathy, maliaise, myalgia, sore throat, headache) 2-4 weeks after inoculation (acute retroviral syndrome). oropharyngeal ulcers and diffuse maculopapular rash - high levels of viral replication (~5 million copies/mL) as the cell mediated and humoral antibody response againist teh virus not yet fully activated, but lab show + viral load and p24 antigen) and with a negative serologic response (neg hiv1/2 ab) = window period humoral response takes 6-8 weeks after initial infection.

23 yr old previously healthy in car accident, lost consciousness at scene but recovered, alert and awake but lost consciousness again, breath smells of alcohol, BP is 130/90, pulse 68 and resp 12. bruise on temple area. left pupil dilated. Imaging show blood where?

epidural hematoma - blood between the skull bone and dura mater. most due to fracture of pterion region (temporal bone with associated scalp contusion) and subsequent rupture of middle meningeal artery epidural hematoma - transient loss of consciousness at time of impact followed by lucid period, eventually get ICP and lead to herniation, coma and death. elevated CIP - mental status, nausea/vomiting, cushing reflex - bradycardia, irregular breathing, hypertension. ipsilateral dilated pupil - due to uncal herniation and oculomotor nerve compression noncontrast CT - hyperdense, biconvex (lens-shaped) mass between brain and skull. dont cross suture.

what is the first line defense for aortic dissection>

esmolol - IV b blocker, selective B1 - first line treatment for acute aortic dissection as has a short half life and reduces shear stress in 2 ways - negative inotrophy dec LV contraction velocity - dec rate of blood ejection and reduce stroke volume to dec rise in BP with each contraction (dec rate and magnitude of bp change) - negative chronotropy dec heart rate, subjecting aortic wall to fewer LV contractions per minute (dec number of bp changes) should also try to dec PVR with nitroprusside, nicardipine should be given before negative chronotropic agent cuz casodilation causes reflex taxy that inc aortic shear stress

the right gastroepiploic

from gastroduodenal artery and perfuse greater curvature of stomach. anastamoses with left gastroepiploic

19 yr old man, punched thru glass window with right arm, profuse bleeding but stopped after pressure, deep laceration at proximal aspect of right cubital fossa, lateral to the medial epicondyl. exam shows absent sensation in lateral palm and palmar surfaces of first 3.5 fingers, inability to flex proximal interphalangeal joints and inability to pronate the foreaem Injury to what is respoonsible for beelding?

has a cubital fossa laceration, median nerve injury, impairment of forearm pronation (pronator teres) and proximal interphalangeal joint flexion (flexor digitorum superficialis) along with sensory deficits in the median distribution. brachial artery is adjacent to th emedian nerve in cubital fossa, inhury to brachial artery most likely cause of bleeding brachial artery is continuation of axillary artery as it extends past the inferior border of teres major border. in upper arm, brachial artery courses in the medial bicipital groove between the biceps brachii and triceps brachii muscles, giving off multiple branches (deep brachial artery) and running alongside both the median and ulnar nerves. proximal to below, median and ulnar nerve diverge, only median accompany brachial artery thru cubital fossa (lateral to medial epicondyle) into proximal anterior foream, which brachial artery splits into radial and ulnar arteries ulnar nerve travel posterior to the medial epicondyle.

12 yr old boy excessing bleeding after tooth extraction, PMH shows painful joint swelling for minor trauma, shoft and non tender abdomen, liver span is 10, spleen not palpable BT is 5 min, appt -25 and pt 23 Def in what?

hemarthroses and excessive bleeding - clotting factor def coagulopathies - deep tissue bleeding into joints, muscles, and subcut tissue platlet defect - mucocutaneous bleeding (epitaxis, petechiae) normal Bt, aptt and prolonged Pt normal BT -- adequate platlet function normal aPTT - intact intrincic prolong PT - defect in extrinsic coagulation pathway -- def in factor 7

30 yr old woman comes to the department with sudden onset abdominal pain and ascites, anemia reticulocytosis, leukopenia, thrombocytopenia, monoclonals ab show def in CD55 and CD59, hepatic vein thrombosis What is the cause of the anemia?

hemolytic anemia, hypercoaguability (hepatic vein thrombosis) and pancytopenia -- paroxysmal nocturnal hemoglobinuria (PNH). hemolysis at low baseline and inc by infection or surgery PNH - acquired mutation in PIGA gene with clonal population of multipotent hematopoietic stem cells. gene is involved in sysntehsis of glycosylphosphatidylinositol (GPI) anchor, a glycoprotein necessary for attachemnt for several service proteins including CD55 ( decay acclerating factor) and CD59 (MAC inhibitory protein) help inactivate complement and prevent the membrane attack complex from forming normal cells absense of gpi anchor reults in cd55 and cd59 deficiency and complement mediated hemolysis. this occurs at night becuz complement activity is increased during sleep due to lower blood ph patients also have thrombotic complications (budd chiari sunrome) due to release of free hemoglobin and other prothrombotic factors from lysed rbcs and platlets pancytopenai and aplastic anemia (due to autoimmune attack again GPI antigens in tem cells flow cyto is gold standard

34 yr old woman, 2 week of palpitationsm excessive sweating and anxiety. obesity taking levothyroxine by friend for weight loss, pulse is 110... what is expected of radioactive iodine uptake, thyroglobulin and t3 levels

high T3 and low iodine uptake and thyroglobulin exogenous thyroxicosis - due to levothyroxine, porcine thryoid extractions. in add to high T4 and surpressed TSh see: Radioactive iodien uptake - correlated with the organification of iodine and syn of new thyroid hormone, endogenous thyroid supressed, see dec blood flow Thyrogobulin - large glycoprotein in thyroid follices that serve as source of tyrosine residues ofr TH syntehsis... small amount released for TH, more with inc synthesis or follucular destruction,.. since exogenous levels are low T3: high becuz converted from t4

50 yr man comes to office for mass on his back, has had mass for several years, inc only slightly during the time, had 2 sinilar lesions, one on his arm and one on leg, they are painless and no other symptms, multiple subcutaneous, soft, freely mobile, nontender masses dx?

lipomas - soft, mobile, subcutaneous mass common benging of subcut fat, in middle aged audlts and stable or enlarge slowly over time, overly epidermis is normal Diagnosis of lipoma is usally eay - excision bipsy can show well differentiated, mature adipocytes with an intact fibrous capule..

48 yr ol dman with right inguinal discomfort, bumps in groin, was treated for gonorrhea but no other probs, right inguinal node are enlarged and tender as nodes in popiteal area distribution in patient would also be seen where?

purulent laceration on the right lateral foot Lymph system in extremities is divided into superficial which follows venous sytem and deep which follows arterial system superficial - lymph from skin and subcut tissue deep - drain both deep muscles and superficial vessels in lower extremities = superficial divided into medial and lateral medial runs along the long saphenous vein up to the superficial inguinal lymph nodes, bypassing the popiteal lateral - drain via lateral track and communicate with popiteal and inguinal nodes - so lymphadenopathy in both

What do selective COX 2 inhbitiors lower risk for?

relieve pain with loewr risk of bleeding and gastric ulceration that nonselective NSAIDS Celecoxib - selective COX 2 inhibitor, potent anti inflammatory effects with elss risk of bleeding and GI ulceration

What does the MCL do?

resist forces that push the knee medially, inc laxity of the knee with valgus stress test indicated injury to the medial collateral ligmanet

what is given after hip surfery as prophylacis for PE?

low molecular weight heparin (enoxaparin) -

peripheral blood smear of megaloblastic anemia

macrocytosis (large RBCs), hypersegmented neutrophils nad large bizarrely shaeped plated presence of even 1 neutrophil with >6 lobes should raise suspesion for megaloblastic anemia neurological is only seen in B12 def fall and gait cuz of loss of proprioception (peripherla nerves, spinal cord - posterior and lateral).

19 yr old man with stabbed in right arm during fight, 4cm transversely over flexor (valor) surface of proximal forearm, nerve that course between flexor digitorum superficialis and profundus is transected, what is impaired?

median nerve C5-T1 via medial and lateral cords via brachial plexus, course with brachial artery between bicep brachii and brachialis before entering the forearm, in anterior - pass between flexor digotrum superficialis and profunus. and pass into hand thru carpal tunnel beneath the flexor retinaculum. Medial nerve injured with carpal tunnel -- pain and numbness in first 3 digits and lateral half of forth, weakness of thumb flexion and opposition. proximal injury - dec sensation over the thenar eminence and weakness of flexion of wrist and 2/3 digits - benediction hand.

47 yr old man at ER due to fever and fatigue, history of HIV and not taking antiretrovirals, temp is 100.9, bp is 110/70, pulse is 103, and resp 20, he has heptosplenomegaly and erythematous papules, lab show pancytopenia. has + histoplasma antigen, IV of amphotericin B given for disseminated histoplasmosis, day later develop palpitations and weakness, ECG shows premature ventricular beats, Drug tox relate d to what?

nephrotoxicity - due to dec in GFR and direct toxic efffects of tubular epithelium. can lead to anemia (dec epo) and electrolyte abnormalities Hypokalemia - hypomagnesia are common due to inc in membrane perm of the distal tubule. Hypokalemia can cause weakness and arrthymias. Hypokalemia - T wave flattening, ST depression, prominent U wave and premature atrial and ventricle contractions. .. can lead to ven tachy or fib.

difference between normal grief and MDD

normal gried pervasive anhedonia, worthlessness and suicidal r not present normal - sadness resolves around feelings of loss and in waves intermixed with positive memories of deceeased... can last 6-12 months following by integration of grief.. more transient but still feel it and have made adaptations

28 yr old woman, 18 weeks gestation comes to office for routine prenatal appointment, feesl find, she just has mild bilateral pedal edema in shina compared to nonprego, what is expected of fibrinogen, protein S and fibrinolysis?

normal pregp -- mild prothrombic state due to: 1. inc procoagulant factors - coagulation in the intrinsic (fac 12) and extrinsin (factor 8) and final comman (fibrinogen) are inc up to 200% which promote the formation of corss linked fibrin clots 2. dec anticoagulant factors - protein S levels decrease, resistance to activated protein C inc, and reduced clotting factor proteolysis 3. reduced fibrinolysis - activity of fibrinolytic inhibitors (plasminogen activator inhbitor 1 derived from the placenta) inc significantly, reduce the breakdown of fibrin clots these protect aganist maternal bleeding during fetal delivery, and seperation of placenta, inc risk of peripartum venous thromboembolism

At what age can u diagnose ADHD?

not before 4-5.

63 yr old man with 3 month of cough with occasional hemoptysis, night sweat, unintnetional weight loss, emigrated from south africa, worked in gold mines, history of silicosis for 10 yrs, PE shows diffuse, fine crackles with right upper lobe predominance, xray shows diffuse small nodules, hilar adenopathy with prominent calcifications, and cavitary lesion in right upper lobe Patient inc. suseptibility why?

silicosis - occupation lung due diease do to inhalation of crystalline silica and characterized by multiple rounded nodules located in the upper lobes, patients also develop calcification of the rim of hilar lymph nodes (eggshell calcification) is associated with inc risk of mycobacterium inf cuz of impaired macrophage function macrophage phagolyosomes are disrupted by internalized silica particles, leading to impaired phagocytosis and inc apoptosis

2 day old dusky, irritable, bp is 70/30 pulse is 148, resp is 68 PE - cyanotic and irritable newborn with mild to moderate resp distress, has continous machine like murmur appreciated between the scapulae serum lactate is elevated, echo shows aorta lying anterior, inferior and to the right of the pulmonary artery. failure of what embryo process caused this?

spiraling Transposition of great arteries due to linear (rather than spiral) devlopment of aorticopulmonary septum in utero, resultin in anteriorly positioned aorta connected to the right ventricle and posterior pulm artery connected to the LV so 2 parallel circulations TGA is incompatible with life unless have a patent foramen ovale, septal defect or PDA to allow for mixing of oxygenated pulm circ with blood with system circ patients may be normal initially but become cyanotic, tachypneic and tachycardic as the PDA (machine like murmur) begins to close, at 1-3 days elevated lactate is cuz of anerobic metabolise in poorly oxygenated blood

What is closed loop communication?

team member repeat back the information received to ensure the correct info has been conveyed, highly effective communication reduces the risk of medical errors in health care setting acknowledger receipt of info and confirm its undertsanding sender should follow up with yes

What does EBV, HIV, and Parvo attachment via?

the inital attachment of the virion envelope or capsid surface protein to the complementary host cell surface receptors is essential to viral tropism for specific tissues and invasion of cells. Many viruses bind to normal host cell plasma membrane receptor to enter host cells. CD4 with HIV gp 120 CD 21 with EBV gp350 Erythrocyte P antigen with parvo B19