sara uworld rando

What does erythema migrans signfy?

hallmark feature of lyme disease, by borrelia burgorferi, transmitted by ixodes scapularis during blood feeding. replicates at site of inoculation and generate rash in 7-14 days after transmission in most patients. EM - begin as a macule that can expand outward as B Burgforferi spread thru the dermis. Most cases evolve over days into annular lesion with central clearing - bulls eye. pain is rare, pruritis is mild or absent. .. can have maliase, fever, headache. Ppl cant remember tick bite, assume in endemic area

What is the most common etiology for cleft lip and palate?

multifactorial inheritence, related to both geneitc and environemtnal factors.

62 yr old man with 4 days of severe, sore throat, difficulty swallowing and hoarseness. he is a farmer, recently been around migrant workers, 101F, 110/60, 116/min, PE shows pharyngeal erythema and edema with coalescing, gray exudate. Bilateral cervical lymph nodes are enlarged and tender. negative for strep. Throat swab culture grows on-spore forming gram + rods, What is helpful in preventing systemic complications of infection?

need a booster every 10 years of vaccine. Due to diptheria toxin - exotoxin that irreversibly inhibit host protein synthesis by ADP-ribosylation of EF2. get pharyngitis, tonsilitis, thick, grey-white pseudomembranes. absorbtion can lead to cardiac myocarditis and neurological complications treat: diptheria antitoxin - preformed, neutralizing antibodies that bind and inactivate circulating toxin. also give penicillin, erythromyocin - reduce continued elaboration of DT from nasopharyneal infection.

2 yr old boy concerned with language development, no birth history. patient sits in the corner, avoiding eye contact with doctor and repeatedly spinning the wheels of a toy truck. he does not respond to his name, makes occasional grunting sounds and says no fully formed words, when his mother tries to take his truck away, he screams and pulls it back. What is the diagnosis?

Autism spectrum disorder lack of social engagemnt, speech delay, reptitive play consistent with autism ASD- more common in boys deficits normally apparent in 2nd year of life, with daignosis befoer after 5. varying degere of language and intellectual impairment. can range from off, stilled speech to delayed or complete lack of intelligible speech. also see imapired joint attention (lack of pointing or bringing objects t oothers), motor sterotypies (hand flapping, spinning) and hyperreactivity or hyporeactivity to sensory input (extreme response to sound or texture, indifference to pain.

What is the process of wound healing?

1. Hemostasis - immediately after injury, small vessel constriction, platlet aggregation, clotting cascade activation that leads to platlet plugging, fibrin clot formation, and cessation of bleeding. Fibrin clot acts a scaffold for subsequent wound healing 2. inflammation.- within hrs, mast cells degranulate, release histamine that inc vascular permeability and promote cellular infiltration (neutrophils, monocytes). Neutriphils digest bacteria, necrotic tissue and foreign debris. Monocyte transform into macrophages, which secrete growth factors (TGF-beta, VEGF) to promote next phase 3. Proliferation - starts during inflammatory phase, for weeks after, leads to replacement of injured or missing tissue: - epithelization - basal keratinocyte proliferation and migration of new epithelial cells form a new superficial epithelial layer that act as a barrier - fibroplasia - fibroblast proliferate and synthesize ground substance and collagen, forming a matrix which capillaries can grow, simultaneous contraction of myofibroblasts (differentiated that produce contractile proteins) help decrease the wound size -angiogenesis - proliferation and migration of endothelial cells from nearby blood vessels lead to ingrowth of new capillaries into the collagen matrix . 4. maturation - final phase of wound healing - collagen remodeling and cross linking, which are primary mechanism by whcih tensile strength of the wound increases.

mechanism by which leukocytes traffic to sites of inflammation and infections What is the process?

1. Margination - inc vascular leakage in the microvascular leads to hemoconcentration and dec wall shear stress, improving contact of neutrophils with endothelial lining 2. Rolling - neutrophils roll on endothelium via loose binding sialyated carb groups, such as Sialyl Lewis X or PSGL-1, to L section on neutrophils or E/P selection on endothelial cells. -- cytokines inc expression of endothelian selectins 3. Activation - slow rolling allow leukocytes to sample the chemokines secreted by the inflamed tissue. this activates integrins by inducing signaling cascade that results in conformational change in integrins necessary for binding 4. tight adhesion and crawiling - neutrophils become firmly attached to endothelium via binding of CD18 b2 integrins (mac 1 and LFA1) to intercellular adhesion molecule (ICAM-1) on endothelial cells. 5. Transmigration - after crawling to the endothelial cell periphery, neutrophils migrate out of the vasculature by squeezing in between the cells via integrin attachments and adherence to platelet endothelial cell adhesion molecule -1 (PECAM-1) -- protein found primary at peripheral intereullar junctions of endothelial cells. 3 leukocyte adhesion deficiency - cant migrate from vasculature to tissues: 1. LAD type 1 - absence of CD18 - inability to synthesis B2 integrins Mac 1 and LFA1 - affecting tight adhesion, crawling, and transmigration... recurrent skin infections wihtout us, delayed detachment of the umbilical cord, poor wound healing 2. LAD type 2 - milder, no delay in umbilical cord and less severe fewer infections 3. LAD type 3 - same as 1 with severe infections and delayed umbilical cord detachemnt, and bleeding complications due affected beta 3 integrins on platlets.

what are the effects of metformin on hepatic gluconeogensis muscle glucose uptake, endogenous insulin production?

1. reduced hepatic gluconeogensis and release of glucose into circulation -- inhibits glycerophosphate dehydrogenase and complex 1 (mito enzymes) which reduce ability of substrates for gluconeogenesis (glycerol, lactate) 2. inc insulin dependent peripheral glucose uptake and utilization 3. reduce circulating lipid levels - metformin upregulates AMP-activated protein kinase in hepatocytes, which inhibits lipogenesis. circulating level of endogenous insulin are unchanged or slightly decreased by metformin, so low risk of hypoglycemia, it reduces caloric intake due to decreased appetite and dec absorption of glucose, leading to modest weight loss in some patients

2 yr old girl with ambiguous genitalia, born with clitoral enlargement and partial fusion of the labioscrotal folds, high blood pressure on 3 visits, is 50th percentile for weight, had hypokalemia, is 46XX. what enzyme is deficient?

11B hydroxylase ambigous genitalia, hypertension and hypokalemia responsible for converting 11-deoxycorticosterone to corticosterone and 11-dexoxycortisol to cortisol. this leads to build up of aldosterone and cortisol precursors -- shunted toward adrenal androgen synthesis. in genetically female infants, androgen excess leads to ambigous genitalia. 11-deoxycorticosterone - is a weak mineral corticoid -- leading to the hypertension and hypokalemia.

1 week old boy with poor feeding, lethargy, unusual muscle movements with left thumb and hand over. last 2 days, vital signs are normal, unusual flexion of left wrist and thumb and extension of fingers are observed with cuff blood pressure measurement. PE shows hypoplastic mandible, low set ears, bifid uvula, cleft palate. Xray.- soft tissue attenuation in the right anterior medistinum. What failed to develop?

22q11.2 microdeletion, - DiGeorge Syndrome Neural crest fail to migrate into the derivatives of the third (affects inferior parathyroid and thymus) and fourth (affects superior parathyroid) pharyngeal/brachial pouches. Parathyroid and thymus hypoplasia -> hypocalecmia and T cell deficiency Hypocalecemia -> inc neuromuscular excitabilty -> tetany, carpopedal spasm or seizures. Chvostek sign - tapping on facial nerve - twictching of the nose and lips Trousseau sign - inflammation of bp cuff leads to carpal sapsm Normally see a thymic shadow, its absence reflects thymic hypoplasia which leads to T cell dysfunction and results in recurrent viral, fungal and protozoa infections Conotruncal cardiac defects - interrupted aortich arch, truncus arteriosus) - failure of neural crest migration. If additional involvemtn of 1/2 pouch --. hypertelorism, short palpebral fissures, micrognathia, bifid uvula, cleft palate

34 yr old russian immigrant comes to the physician with 2 months history of exertional dyspnea and progressive lower extremity swelling, he has abdominal distension and decreased appetide. has gained 10lbs over 2 months, pmh - htn, recurrent lung infections requiring prolonged antibitoic therapy. no history of CAD. smoked for past 15 years. What are the different segements of venous catheter?

3 positive - a, c, v a - atrial contraction c- bulging of the tricupside valve into the right atrium during early systole v- passive increase in pressure and volume of right atrium as it fills in late systole and early diastole. Trophs - X and Y descent x - relaxation of right atrium y- abrupt decrease of right atrial pressure during early diastole after tricupside valve opens and right ventricle begins to passively fill.

What are amingoglycosides moa?

AGs irreversibly bind to bacterial 30S but not eukaryotic 40s. cause genetic code misreading and bacterial protein synthesis inhibition. appear to impact translocation, where aminoacyl-tRNA is shifting from the ribosomal a site (after initial binding) to the P site (after AA incorporation into the peptide chain during elongation) to the E site (after AA cleaving from tRNA) The initial N-formylmethionine-tRNA notably bind at the P site. In prokayotes - unique mRNA (shine-delgarno) located upstread of initiation codon (AUG), which recognizes an N-formylmethionine-tRNA. -- this sequence allows binding of the 30S to mRNA and n-formylmethionine-tRNA (forming the 30s initiation complex). the energy- GTP hydrolysis - brings the 50s into the initiation complex, resulting in 70s ribosomal unit.

23 yr old man is evaluated for excessive bruising since childhood. he saya some family members bleed easiy and sometimes require blood transfusions. temp is 98.1F, PE is unremarkable. CBC unremarkable. Platlet aggregomtery is abnormal -- a defect in platlet surface glycoprotein that normally binds fibrinogen to support platelet aggregation. The abnormal glycoprotein found in this patient is most likely targed by what medication?

Abciximab patient has Glanzmann thrombasthenia - AR disorder that is caused by deficient or defective glycoprotein GP 2b/3a. on platlet surfaces and typically presents in childhood with mucocutaneous bleeding. peripheral smear will show no platlet clumpin - important for diagnosis platlets are responsible for formation of platlet plugs that stop bleeding - primary hemostasis. vessel wall injury exposes the subendothelial collagen and matrix. platlet attachment to exposed collagen is strengthened by GP1b binding to von willebrand factor on vessel wall. the resulting platelet activation leads to - release of mediatos (ADP, thromboxane A2 into circulation, which in turn activates other platlets) - conformational structural change of GP 2b/3a on plalet surfaces, allow thousands of copies of gp2b/3a to bind fibringogen forming the platlet plug Abciximab - gp2b/3a receptor antagonist - inhibit binding of receptor to fibrinogen... used for unstable angina and acute coronary syndrome, in patients with precutaneous coronary intervention.

59 yr old man with hypercholesterolemia, diabetes, and htn come to phycian for follow up 3 weeks after starting a new medication, no new compliants, blood work shows inc in serum potassium 4.8 to 5.2, and creatinine clearance 1.2 -> 1.6. What medication is responsible for these changes?

Ace inhibitor - hypertension, heart failure, renal failure with or withour proteinuria. GFR will decrease orginally, not concerning unless >30% becuz o flong term benefit. AE - hyperkalemia and cough they decrease GFR by preventing constiction of efferent arteriole. CATCHH C- cough A- angioedema T - teratogen (renal malformations) C- inc Creatinine, dec GFR H - hyperkalemia H- hypotension

22 yr old woman comes to the ER due to fever and sore throat, she has graves disease, she recently began taking antithryoid medication. no other medical conditions, she works as a teacher at an elementary school. 102F, 110/70, 90/min, PE shows erythematous pharynx and normal sized thryoid. This no tremor of outstretched hands What is the cause?

Antithyroid drugs - PTU, methimazole - inhibit thyroid peroxidase and used to dec thyroid hormone production in patients with hyperthyroidism (graves disease) inc risk for agranulocytosis, in the first few months of therapy. patients with drug induced agranulocytosis (absolute neutrophil count <500) are at a risk for severe infection. oropharyngeal infection (sore throat, fever, oral ulcerations) - most common manifestation, sepsis can develop quickly after. CBC with differential will show neutropenia without anemia or thrombocyopenia. bone marrow biopsy will reveal a reduction in granulocyte precursors. agranulocytosis is reversible with discontinuation of the drug.

54 yr old man with blood in urine and abdominal discomfort that occured 2 days ago, moving potted plants around and started to have pain in abdomen. said blood in urine resolved in 1 day. history of htn. CT shows cyst in kidney what is diagnosis?

Autosomal dominant (adult) polycystic kidney disease.- mutations in polycystin genes (PKD1/2), result in cystic enlargement of the kidneys and progressive renal dysfunction. Clinical features.- hypertension, abdomina/flank pain, and gross hematuria; extrarenal - liver cysts and intracranial aneurysms. patients are asymptomatic until 4 and 5th decade of life, when relentless enlargement of cysts being to impair renal functions; hypertension is often earliest clinical sign. stretch of the renal cpsul and dilation/rupture of the cysts - abdominal/flank pain. cyst rupture - gross hematuria. worsen with age with 50% at ESRD by 70.

15 yr old girl with recurrent epsiodes of focal onset seizures evolving to bilateral tonic clonic over past several months, has headaches to keep her home. What is the histo path finds for abnormal lesion?

Cerebral arteriovenous malformation AVM - vascular malformation in which blood course directly from the arterise to the veins without passing thru an intervening capillary bed. These tangles vessels with turbulent flow can lead to aneurysm development, bleeding and damage to the surrounding brain. microscopy of the AVM show abnormal vessels, including irregular arteries and large veins with thickened walls and gliotic brain tissue. preesnt in children and young adults with headaches and seizures as well as intracranial hemorrhage (intraparenchymal, subarachnoid hemorrhage) - can be asymptomatic--- nest of abnormal vessesl with "bag of worms" appearnce may be sen on angiography MRI may reveal prior hemorrhage and multiple dark flow voids, indicative of swift blood flow.

29 yr old with right leg injury after cycking, pain lower leg, cant bear weight. right tibial and fibular shaft fracture, undergoe s closed reduction and immobilization of fractures. hrs later - inc severe pain in his right leg. PE shows inc tension within the anterior compartment. What is compromised as a acute complication?

Deep peroneal nerve Acute compartment syndrome - due to long bone fractures, crush injury, thermal injury, nontramatic cause (bleeding disorder, valvular disorder) most common site - anterior comparment of the leg, includes the foot extensor muscles, anterior tibial artery and deep peroneal (fibular) nerve) injury to deep peroneal (fibular) nerve causes dec sensation between the first and second toes, dec dorsiflexion of the foot, foot drop and claw foot.

54 year old white man with progressive neurological disorder, what part of the brain is affect by Wilson disease?

Cystic degeneration of the putamen is most by Wilson disease Putamen - immediately medial to the insula and lateral to the globus pallidus and internal capsule. putamen and caudate are part of the basal ganglia. internal capsule - white matter than seperates the putamen and globus pallidus from the caudate nucleus anteriorly and from the thalamus posteriorly on coronal sections

what drug inhibits dipeptidyl peptidase-4?

Glucagon like peptide 1 - secreted by intestinal L cells in response to food intake and regulates glucose levels by slowing gastric emptying, surpressing glucagon secretion, and increasing glucose dependent insulin release. it acts through cell surface receptors that are coupled with a G-protein adenyl cyclase. Native GLP-1 is degraded by dipeptidyl peptidase (DPP-4) DDP-4 inhibitors (sitagliptin, saxagliptin) inhibit degradation of GLP-1, prolong effect leading to improved glycemic control (reduction in hba1c) GLP 1 effect on insulin secretion is glucose dependent; as glucose levels fall, so does insulin secretion. therefore DPP-4 inhibitiors have a low risk of hypoglycemia. major side effects - nasopharyngitis and upper resp tract symtps GLP-1 agonists are intrinsically resistant to degradation of DPP-4 and can lower blood gucose with a low risk of hypoglycemia

experimental animals are immunized to protein fragments dervied from peripheral nerve myelin. subsequent analysis finds evidence of T-cell response as well as production of autoantibodies aganist nonprotein antigens. this leads to segmental demyelination of peripheral nerves in the animals. the experimentally induced condition i smost analgus with what?

Guillian barre syndrome demyelination of peripheral nerves in response to immune challenge with myelin-like substance is a pathogenic mechanism similar to GBS. thought o be due to molecular mimicry, in which an infectious agent contains ganglioside-like substance in its lps layer. antibodies formed aganist this substance and activated T cells cross react with ganglioside components of myelin and schwann cells. segmental demyelination and an endoneurial inflammatory infiltrate composed of lymphocytes and macrophages are seen on light microscopy GBS manifests as ascending, symmetric muscle weakness that often occurs after GI (campylobacter jejuni) or URTI. DTRS r decreased or absent and paralysis may ascend to the cranial nerve (particularly CN7) paralysis of respiratory muscle is fatal with supportive care

Autopsy on 4 year old boy with died of MI, history of intellectual diability, prominent forehead, broad nose, daze over cornea bilaterally, heart, liver, and spleen are enlarged. Sampling of coronary arteries show accumulation of what?

Heperan sulfate Hurler Syndrome (type 1 mucopolysaccharidosis) -AR -- intellectual disability, corneal clouding, coarse facial features (frontal bossing, broad nose, flat midface). hepatosplenomegaly and heart disease. death is normally caused by cardiac complications (MI) - deposition of dermatan and heperan sulfate in vessels. def: Alpha-L-iduronidase - hydrolyse dermatan and heparan sulfate. "L" - HurLer.. AR Hunter syndrome is less severe- same accumulation but no corneal clouding. Hunter - 2 Ts - Iduronate -2- sulfatase - hunter is XLR -- hunting use the X and also ur eyes.

62 yr old man with poor medical, cant see, blurry vision for the last 2 weeks, noticed a shadow develop suddenly across the visual field of his right eye, no recent headaches, double vision, vertigo, light sensitivity or nausea, pupils are equal and reactive to light. Visual field testing shows patchy loss of vision. Flame shaped retinal hemorrhage in the right eye is noted. What is the cause of the visual distrubance?

Hypertension Hypertensive retinal hemorrhage causes painless, unilateral visual disturbances, ranging from mild obscuration without loss of visual acuity to permanent blindness. Severe hypertension in retinal precapillary arteriorles cause endothelial disruption, leakage of plasma into the anterior wall, and fibrinous necrosis. necrotic vessels can bleed into the nerve fiber layers, causing dot and flame shaped hemorrhages will aslso see thickening of arteriolar walls (copper or silver wiring), compression of the associated veins (artervenous nicking) and small, white foci of retinal ischemia (cotton wool spots)

what is splitting?

Immature defense mechanism. experiencing the self of others in extremes, either all positive or all negative. which allow bad qualities to be completely seperated from the good. often seen in borderline personaility disorder - constribute to unstable relationships and mood instability

What is the intrapleural pressure at resting equilibrium?

In the pressure volume curve - collapsing pressure is positive and expanding pressure is negative. The lungs have a tendancy to collapse at all lung volumes - so entire cruve in collapse force. the resting chest wall has a tendency to expand at all but very high lung volumes. The point where collapsing force of lungs and expanding force of chest wall are equivalent is the resting equilibrium of the resp system aka the end-tidal expiration. at this point - the alveolar pressure is equivalent to atmospheric pressure 0 cm H20) and lung volume is at function residual capacity (ER + ERV). Compliance is teh cahnge in vol per change in pressure and is represented by the slope of the pressure-vol curve. more compliant can stretch to accomodate large inc in vol with little change in pressure-- steep complance curve lungs are most compliant at FRC and dec and very high and very low volumes the chest wall has low compliance at low lung volumes and becomes more compliant as lung vol inc with inspiration Intrapleural pressures are not repreesnted on the lung pressure vol cruve. the expanding for of the chest wall working in opposition of collapsing force of lungs creates a negative intrapleural pressure throughout the resp cycle. inspiration - expansion of chest wall, generates even greater intrapleural negative pressure and pull the lungs outward. negative pressure peak at max inspiration at -8 During passive expiration - the chest wall relax and resp goes back to equilibrium - intrapleural pressure is about -5 cm.

What is passive aggressive?

Indirect expression of anger.. rather than directly expressing feelings. procrastination, forgetfullness, purposeful inefficiency, backhanded compliements, sarcasm, denial of being angry

15 yr old girl with sudden onset severe left leg pain, was practicing for gymastics heard a pop after landing and developed anterior left leg pain. she can now not bear weight, she has swelling of left knee with focal tenderness just above the patella. cant raise her leg aganist resistance. she has a complete tear of quadriceps tendon but no fractures. Lidocaine injection near which site would provide adequate anesthsia for procedure?

Inguinal ligament Femoral nerve L2-L4 - innervate the quads (enabling extension at the knee and flexion at the hip) and sensation to the arch of the foot, shin and anteriomedial thigh nerve comes between psoas and iliacus muscle and passes under the inguinal ligament (lateral to femoral artery) into the thigh before branching into femoral triangle into an anterior and posterior devion Best place for femoral nerve block - is right below the inguinal ligament.. this will anestheisze the anterior thigh knee and femur. will also block structures supplied by the saphenous nerve (terminal extension of femoral nerve) to dec sen to medial leg below the knee.

what is the histo for diabetic nephropathy?

Kimmelstiel-Wilson (KW) nodules - location in peripheral mesangium - ovoid or spherical shape -lamllated apperance -eosinophilic (h and E stain) - periodic PAS + Nodular glomerulosclerosis, characterized by glomerular basement membrane thickening and increased mesangial matrix deposition. over time, expansion of the mesangium and KW nodule formation compress the glomerular capillaries and cause loss of glomerular function. Patients have progressive proteinuria that cna lead to nephortic syndrome (peripheral edema, heavy proteinuira, fatty casts), hypertension, renal failure.. urine is normally bland.

52 yr old woman, recurrent right lower extemity swelling, pain and erythema. has dm2 and depression, meds are metformin, paroxetine, and mulitvitamin. Diagnosed with cellulitis, admitted to hospital and started on antibiotics. 3 days later, is agitated, delerious, with abdominal cramps and diarrhea. 180/100, 102.6, 120/min and regular. diaphoretic and tremulous and pupils are dilated bilateral hyperrflecia and ankle clonus. begins to have seizures, which ab was the patient most likely given to treat cellulitis?

Linezolid treat infections of gram + bacteria, particulary vancomyocin resistant enterococcus and methicillin resistant staphlococcus aureus. linezolid has MAOI activity - can precipiate serotonin syndrome with concomitant use of SSRI (paroxetine) or other serotongegic meds. serotoninc effect is inc with monoamine oxidase inhibitor (MAOI) combined with serotenergic antidpressant - SSRI, SNRI or TCA serotonin syndrome - autonomic instability - hyperthermia, hypertension, tachycardia, altered mental status (agitation, confusion), and neuromuscular hyperactiivty (tremor, hyperreflecia, myoclonus), gi symptoms and diaphoresis due to increased serotonergic effect (5-HT1A and 5-HT2A receptor stimulation).

12 yr old girl with recurrent episodes of self limited colicky abdominal pain and nausea lasting several days. recently hospitalized for episode of difficulty breahting. no pmh, her mother has history of attacks of severe abdominal pain and diarrhea. PE is unremarkable labs show dec serum C4 and C1 esterase inhibitor levels. What drug is contraindicated?

Low serum levels of C1 esterase inhibitor (and C4 - the substrate) = herediatary angioedema - AD - painless non pitting well circumscribed edema. face, lips and tongue most often effects but can involve internal organs. angioedema affecting the tracheobronchial tree can cause resp obstruction and is potentially fatal. angioedema in gi tract - abdominal pain, vomiting, and diarrhea normally - C1 esterase inhibitor suppress activation of C1 complement compoenent and therefore rest of classic complement pathway. it also inactivate kallikrein, catalyzes conversion of kininogen to bradykinin. in hereditary angioedema, low C1 esterase inhibitor leads to inc in active kallikrein and bradykinin levels Bradykinin along with c3a and c5a mediate angioedema by increasing vasodilation and vasodilation Angioedmea -- common side effect of ACE inhibitors... ACE converts bradkykinin into inactive metabolites. ACE inhibitors can elad to bradykinin accumulations.. double wammy

Elderly patient is diagnosed with aggressive non-hodkgin lymphoma. tumor cells stain for CD20 marker, what biological agent can be added to chemo regimen to improve treatment response?

Rituximab Biological response modifers - antibodies, cytokines and other substance intended to restore or induce the immune system ability to overcome disease. CD20 - Rituximan is a mab used in lymphoma that specifically target the CD20 surface immunoglobulin.

What occurs with failure of neural tube closure?

Midline fusion of neural folds create the neural tube during the 3rd week of fetal life. neural tube structure is connected to the amniotic cavity by the openings at the ends known as anterior and posterior neuropores. Failure of neuropore closure by 4th weeks leads to neural tube defects (NTDS) anterior NTD - anencephaly (absence of the forebrain) and encephalocele (protrusion of neural tissue thru the cranial defect). Posterior NTD - include spina bifida occulta, meningocele, and meningomyelocele. meningocele and menigomyelocele present as a cystic mass at the lower spine covered with skin and sometimes a tuft of hair. meningocele - spinal meninges that protrude thru the vertebral arch defect Meningomyelocele - portion of spinal cord or cauda ewina within the protruding menigneal sac. prenatal valproate use for bipolar disorder or epilepsy -- 10-20x inc of NTD due to impaired folate metalbolism, also folate antagonists (methrotrexate, trimethoprim-sulfamethoxazole) give folate B9

20 yr old man with pain in left thigh, 3 months ago, a horse kicked him in the left midthigh, resulting in deep pain and swelling in the thigh muscles, xray was normal, over last few days, symptoms resolved with rest and ice packs. few weeks later, gradually developed recurrent pain and swelling in the same area. exam shows solitary, hard, mobile, oval mass of approximately 4x5 cm in the anterior aspect of the left thigh. excision of the mass is performed. Histo will show what?

Myositis ossificans - formation of lamellar bone in the extraskeletal tissues (heterotrophic ossification). MO is typically triggered by severe (fracture or muscle contusion) or recurrent trauma that initates the expression of bone morphogenic proteins, which promote in-migration of spindle stem cells. These cells differentiate to fibroblasts - produce collagen and ecm - and subsequently to chondrocytes and osteoblasts (responsible for production of osteoid and mineralization). MO - painful, firm, mobile mass. most common in the quadriceps and brachialis muscles but can occur elsewhere xray show intramusclar calcification with radiolucent zones (eggshell calcification). Histo - zonal pattern with other areas of relatively mature bone (benign metaplastic bone tissue) and inner region of fibroblastic proliferation (without mitotic atypia) and variable amounts of collagen and osteoid.

48 yr old woman, painless left breast mass. PE shows 4cm mass with dimpling of the overlying skin, left axillary lymphadenopathy notes, she has soft tissue calcifications. biopsy shows invasive ductal carcinoma. IHC - negative for estrogen/progesterone but overexpress her2 epidermal growth factor receptor. Treated with a monoclonal ab that binds the extracellular domain of the growth factor receptor. Repeat evaluation 6 weeks shows a decrease in the size of the mass. What host factors are responsible for mediating the response to the mab therapy?

Natural killer cells and granzymes her2 - epidermal growth factor overexpressed in aggressive breast cancer. Treatment with mab - trastuzamb - target HER2 surface receptor often results in tumor regression. -- can signal cancer cell death thru receptor downregulation, complement deposition -- MOST -- antibody dependent cellular toxicity (ADCC) ADCC: - naturally occuring or monoclonal igG binds complementary surface antigen on a host or foreign cell. - patrolling NK cells bind Fc poriton of igG using CD16 - binding trigger NK release of granules - perforin and granzymes (proteases) that induce apoptosis/osmotic lysis of the antibody bound cell NK - part of innate immune response- do no engage in MHC complexes to different self from nonself. unlike cytotoxic T cells - NK cells can identify neoplasms that have downregulated surface expression of MHC1 molecules.

59 yr old woman, fever, skin flushing, altered level of consciousness. 50/20, 120/min, despite IV fluids. If blood is positive for E.coli, what bacterial factors is most directly responsible for patient current condition?

Patient is in septic shock (fluid refractory hypotension) - due to bacterial endotoxins into the blood stream. Endotoxins are in the outer membrane of gram - bacteria, made of LPS -- LPS is long, heat stable made of three regions: O antigen - just used for identification of diffrent strains Core polysaccharide Lipid A - toxic to mammalian cells and act like a virulence factor by inducing release of endogenous pyrogens (Il-1, prostaglandins) and inflammatory mediators (TNF alpha, interferon) from activated macrophages. These cytokines cause manifestations of septic shock - fever, hypotension, inc vascular permeability with third spacing of fluids and organ failure. Can also produce -K:1 - capsule - defense aganist phagocytosis by immune cells and does not directly contribute to shock Fimbriae or pilli - adherence to target tissue Heat stable exotocin - enterotoxin produced by Enterotoxicgenic E coli - secretory diarrhea

40 yr old woman, preg 4x baby 4x, anemia, week ago was seen in ER due to fatigue, sob, and increasingly heavy irregular period, lab showed hemoglobin of 5.4, after transfusion with packed red blood cells, her follow up hemoglobin was 7.8 prior to discharge. since then, energy and breathing have improved, no futher menstraul bleeding now has yellowing of the eyes and face over last day, no hepatosplenomegaly. labs show hemoglobin 5.9, reticulocutes 7%, total bilirubin 3.8 The patient current symptoms are most likely do the what antibody antigen reaction?

Patients antibodies aganist the blood product minor red blood cell antigen Patient has jaundice and hemolytic anemia a week after transfusion, finding suggestive of delayed hemolytic transfusion reaction (DHTR). ppl previously exposed to antigen, minor red bool cell antigen (non-ABO) via pregnancy, prior transfusion, or IV drug use. during first exposure, low typically undetectable ab response reexposure via transfusion - patient memory of B cells produced a larger surge of antibodies, resulting in detectable hemolysis = amamnestic response DHTR - mild and develop >24 hrs after transfusion - most common 1-2 weeks after mostly asymptomatic, detected with +newly positive coombs test and antibody screen. Addtional labs - anemia with compensentary reticulocytosis, evidence of hemolysis (inc indirect bilirubin and inc lactate dehydrogenase)

23 yr old man with Dm1, confusion and weakness, mild diarrhea 2 days ago, missed some insulin and appetite is poor, on exam fruity odor to breathe. What urine chemistry? Ph, Hco3, H2Po4

Ph and hco3 decreased H2po4 increased Diabetic ketoacidosis - metabolic acidosis - dec serum ph and bicarb, with compenensatory dec in pc02. Try to correct by: 1. increased HCo3 reabsorption - carbonic anhydrase in proximal tubular lumen faciliate reabsorbtion of filtered bicarb, each reabsorb bicarb is equivalent to secretion of of a H+. in metabolic acidosis will be completely reabsorbed 2. increased H+ secretion - acidosis inc H+ secretion throughout the nephron. however, pH changes rapidly with relatively small changes in H+ conc, limiting the amount of acid that can be secreted as free H+ 3. Increased acid buffer excretion - to excrete more acid, kidney utilize acid buffer to trap H+ without markedly lowering urinary pH. 2 acid buffers in urine: HPO4s and NH3. -- which combine with H+ to form H2PO4 and NH4+ in chronic acidosis, proximal tubular cells greatly increase production of NH3 to increase acid excretion

What is the MOA of verapamil? waht are the effects?

Phase 4 - spontaneous depol - begins after hyperpol triggers oppening of HCN channels that allow influx of Na (funny current) T type (transient) ca channels open once the membrane potential becomes more +, allowing Ca influx to contribute to depol. as approach threshold (L type.- long lasting) ca channel begin to open, futher inc Ca influx and significantly decrease the time until threshold reached Phase 0 - upstroke - continued opening of L type. phase 3 - repol - opening of K channels and efflux of K from the cell in conjuction with closer of L type Ca channels Class 4 antiarrythmics (verapamil, dilitiazem) - prevent recurrent nodal tachyarrhythmias such as PVST. block the L-type calcium channles in cardiac slow response tissues - which slows phase 4 depol - reduce conduction velocity in SA and AV.

26 yr old woman with acute onset diplopia, has had episodes of blurry vision involving her right eye that occured 6 months and 2 years ago. were associated with deficiet in color vision and pain made worse with an eyemovement. Recovered in a few months in both cases, on exam - mild right optic disk atrophy, relative afferent pupillary defect in the right eye. There is slowed and impaired adduction of the left eye with right lateral gaze. convergence shows normal adduction in both eyes Diploplia is caused by what?

Reduced saltatory condction She internuclear opthalmoplegia (impaired adduction on the left with right lateral gaze), this with prior episodes of optic neuritis (transient blurred vision and eye pain with movement ) -- multiple sclerosis - demyelinated disease of CNS caused by autoimmune reponse directed at oligodendrocytes in unmyelinated neurons, signal transmission required sequential activation of adjacent sodium channels down the entire length of the axon. In myelinated neurons, the depolarization impulse is regenerated at discrete points along the axon (nodes of Ranvier) where sodium channels are concentrated The myelin sheath serves as an electrical insulator that results in impulse "jumping" between 2 adjacent nodes salatory conduction) due to acute demyelination with MS, propogation of the impulse cant occur, as the distance between sodium channels at the nodes of ranvier preclude sequential activation ... this causes conduction block. overtime, sodium channels eventually redistribute across the naken axon and surviving oligodendrocytes partially remyelinate neurons, allowing some restoration of signal transmission (thats why some MS resolve to a certain extent).

34 yr old man with dizziness and mild confusion over the last week, history of seizures beginning in childhood and recently started on carbamazepine by her neurologist. temp is 98, bp is 121/72 and pulse is 68, resp 13/min. PE is in normal. labs show low serum sodium concentration. it is determined that the patients condition is cause dby inc release of a hormone that is cosecreted with neurophysins, this hormone is secreted into the circulation by what?

SIADH - can be caused by many drugs unincluding carbamazepine, cyclophosphamide, ssri's. ADH (vasopressin) and oxytoxin are synthesized within magnocellular neurons found in the supraoptic and paraventricular nuclei of the hypothalamus. Most magnocellular neurons produce either vasopressin or oxytocin. Once translated, there hormones are packaged into vesicles and travel via anterograde axonal transport to the posterior pit. there, hypothalmic axons terminate into herring bodies, which are specialized nerve terminals that act as storage sites for the secretory vesicles. these vesicles contain proteins known as neurophysins that are involved in posttranslational hormone processing and stabliization during axonal transport. vasopressin and oxytocin and their associated neurophysins are secreted from post pit into hypophysial vein to enter the systemic circulation.

Researcher studying a neuronal protein that primarily exist in alpha-helical secondary structure is found in beta sheet conformation, it is resistant to protease and accumulated in large quantities within the cells. Futher investigation shows abnormal isoform can perpetually induce the same conformational change within normally folded proteins. What is seen on histopath?

Sponge-like vacuolated neurons in gray matter Prion disease - neurodenerative cause dby accumulation of an abnormally folded protein in the brain, can been in humans - creutzfelt-jacob, fatal familial insominia, Kuru and animals - scarpie, bovine spongiform encephalopathy can be transmitted thru tainted meat Prion proteins both in neural and non brain cells and exist in normal alpha helical tstructure (PrPc), prior disease occurs after conformational change from the alpha helix into the beta-pleated sheet isoform (PrPsc-scarpie) -- which has ability to induce similar conformational changes in other proteins The beta sheet conformation is resisant to proteases and forms, long highly neurotoxic fibriils, which accumulate intracellularlu in neurons and form extracellular depotis on micro - spongiform degeneration of gray matter, formation of microscopic vacuoles within neuronal processes. Extracellular prion accumulations (kuru plaques) frequently present and stain with congo red and periodic acid schiff stains

64 yr old man with chest discomfort and sob. hypertension, dm2, severe OA of left knee, smoker for 20 pack year, undergoes dobutamine infusion with simultaneous cardiac imaging before infusion - normal LV contractility - EF 60% during - dec. apical contractility, EF 45% 5 min after - normal LV contractility - EF 60% What is the explanation?

Stable angina - fixed coronary artery stenosis in setting of atherosclerotic coronary artery disease., limiti blood supply to myocardium, which during exercise or period of inc myocardial demand like mismatch of oxygen supply and demand = chest pain, sob pharmological stress testing - Dobutamine - beta1 agonist - inc HR and contractility to mimic the increase in myocardial oxygen demand that occurs with exercise if unstable and cant meet demand will see transient decrease in contractility (wall motion defect) often leading to reduced ejection fraction if transient wall defect is localized to the cardiac apex - most likely fixed lesion that limit blood flow to that area of myocardium

54 yr old man with worsening fever, cough, sob. presented 1 week ago with fever, headache, myalgia, nasal discharge, and a sore throat. tested Positive for influenza A. The symptoms improved but past 2 days, has had high fevers, cough productive of yellowish sputum, sharp right sided chest pain, sob. 102F, 118/66, pulse is 110. PE shows right sided crackles, infiltrates in the right upper lobe. What pathogen is isolated?

Staphylococcus aurues Influenza virus - attack the tracheobronchial epithelium and result in dec cell size and loss of cilia-- promoting bacterial colonization. the influenza surface protein neuraminidase also cleave sialic acid off host glycoproteins, leading to inc free sugar in resp tract, which foster bacterial frowth. so at risk for secondary bacterial infections most causes - Strepococcus pneumoniae, staphylococcus aureus, haemophilius influenzae. S, aureus in young; old people norm get pneumonia.

25 yr old man, facial acne. no pmh, no social history, works as a personal trainer, fam his for DM in mother and leukemia in father, 134/82, 58/min, PE - mild facial acne. liver is 8cm, spleen is not palpable, testes are soft and testicular volume is decreased. labs: hematocrit -60% wbc - 7500 platlet -225k esr - 15 serum creatinine - 1.2 bun - 18 What is explanation for abnormal labs

Steriod drug use acne, testicular atrophy, erythrocytosis, == androgenic steriod abuse testosterone stimulates RBC production, -- higher hematocrit in males compared to females, exagerated with exogenous androgen use, inc hematocrit in a dose dependent manner androgens dec gnrh, results in testicular atrophy and dec sperm production. virilization in women (clitomegaly, hirutism) and acne

airway resistance of the lower respiratory tract

airway resistance at each level of the lower resp tract is inversely related to the total cross sectional area. airway resistance is high in the trachea and reaches a peak in the medium sized bronchus, where total cross sectional area is low. air resistance then progressively dec as total cross sectional area increase thru the smaller bronchioles, terminal bronchioles and alveoli.

6 month old, undescended right testes, PE shows absence of palpable right testis in the scrotal sac. has a round mass palpated superior to the scrotum in the inguinal canal. Orchiplexy, placement and fixation of the testis in the scrotum, recommended. During procedure, malpositioned testis will most likely be pulled thru the psycholigc opening in which of the following structures?

Testicles develop in the fetal abdomen during organosgenesis between 8 weeks and full term, each testic descend from the abdomen into the inguinal canal thru the deep inguinal ring, which is opening in transversalis fascia bounded laterally by the transversus abdominis muscle and medially by the inferior epigastric vessels. Each testis then passes anteromedially thru the canal and enters the scrotum via the superficial inguinal ring, which is the physiological opening the external oblique muscle aponeurosis crytorchidism - failure of one or both testes to descend to the scrotum before birth which occurs more commonly in pretem neonates. it is associated with signifcantly inc risk of testicular cancer and infertility. normal descend spontaneously by age of 6 months, if not require surgical intervention

56 yr old woman, follow up for DM2. She is managing her condition with a healthy diet and regular exercise on max tolerated dose of metformin. not controlled for 6 months, with an average fasting glucose of 170 mg/dL, A1c 8.0%, has no diabetes related complcications, she taks lisinopril and amlodipine. after various meds, she decided to tadd pioglitazone, before starting what AE should she be counseled on?

Thiazolidinediones (TZDs) activate peroxisome proliferator-activated receptor gamma (PPAR-gamma) - transcriptional regulator that affects expression of genes involved in glucose and lipid metabolism can takes days to week to see change since is dependet on transcription and protein synthesis main AE: fluid retention due to inc sodium reabsorption in the renal collecting tubules nad inc vascular permeability in adipose tissue. This can cause water weight gain, peripheral edema, and decompensation of underlying congestive heart failure fluid retnetion is often worse when tzds are given with insulin also cause adipose weight gain, due to inc fat storage in adipocytes and inc number of adipocytes in subcutaneous tissue

63 yr old man hospitalied for COPD exacerbation delveops hypercapnia respiratory failure. Transfered to ICU and undergoes intubation after premediation with muslce relaxant succinyline. What is the procesS?

Train of four stimulation - used during anestheia to assess degree of paralysis induced by NMJ blocking agents. a peripheral nerve stimulated 4 times in quick sucession and muscular repsonse is recorded. the height of each bar represents the strength of each twitch; higher bars indicate the activation of inc number of individual muscle fibers (myocytes) when the nondepolarizing NMJ blocker (vercuronium) is admin, competitive inhibition of postsynapic acetylcholine receptors at the motor endplate prevents some of these fibers form activiting, dec the strength of the twitch. TOF stimulation shows a progressive reduction in each of the 4 (fading pattern) as a result of less ach being released with each subsequent impulse (due to additional effect of presynatpic ach receptor blockade) in contrast -- depolarizing blockers (succinylcholine) initially funciton by preventing repolarization of the motor endplate and show equal reduction of all 4 twitches during TOF stimulation (phase 1 block) the response remains equal bcuz presynaptic ach receptor stimulation helps to mobilize presynaptic ach vesicles for release. persisent exposure to succinylcholine results in eventual transition to phase 2 blockade as ach becomes desensitiized and inactivated -- similar to nondepolarizing blockade succinylchoiline is commonly admin for rapid-sequence intubation - due to rapid onset (<1 min), the duration of action is determied by its metabolism by plasma cholinesterase and < 10min. if homozygous for atypical plasma cholinesterase - break down more slowly-- patients have paralysis for hours.

What is the function of M protein in strep group A? what does it resemble?

gram + organisms - cells wall made of thick peptidoglycan layer and teichoic acid. Strep pyogense - has M protein, inhibits phagocytosis, prevent complement binding, and aid in epithelial attachment. M protein is alpha helical coiled protein- similar to myosin and tropomyosin. in some patients - protective AB aganist M protein that develop in S pyogens can cross react with myosin epitopes leading rheumatic carditis.

34 yr old man with heart murmur, no chest pain, palpitations dizziness or sob at res. he exercises regularly without any abnormal symptoms. cardiac ausculattion in the second right intercostal space reveals an ejection clikc along with soft systolic murmur radiating to the neck. What part of LV PV curve shows opening of the valve?

bicupsid aortic valve - asymptomatic with soft systolic ejection murmur at right second intercostal sapce Aortic valve opening occurs when the LV pressure exceeds the central aortic pressure at the end of isovolumetric contraction. LV pressure rise until forward blood flow into the aorta, until the pressure in the LV fall below the aorta leading to aortic valve closure

72 yr old man disoriented and wandering in the street. pmh - dementia,htn and stroke. PE.- disorented, thin appearing male, his gingivae are swollen and bleed easily. ecchymoses are noted on legs. labs low hemoglobin, normal platlets, wbc, elevated bun, normal PT, PTT, and creatinine What is responsible for condition?

Water soluble vitamin deficiency Vitamin C - ascorbic acid - water soluble vitamin that functions as a cofactor in numerus biochemical proceses, including collagen synthesis. def in vitamin C "scruvy" is most commonly due to insufficient intake, -- chronic drug or alcohol abuse, malnourishment or old age. cutatenous signs - phrynoderma (perifollicular hyperkeratosis), coiled hair, and poor wound healing. will see bleeding gums and loose teeth. hemorrhagic complications include ecchyomoses and petechiae, hemarthrosis, intramuscular bleeding and bleeding iwthin the CNS, gi and GU. normocytic, normochromic anema is typical while PT and PTT are normal

how do u diganois tetanus?

a clinical diagnosis, C. tetani only grows at inoculation site (clinical syndrome stems from toxin elaboration not bacterial invasion). Wound cultures can provide supportive evidence but take several days to retun and are urally not perfomed. Tetanus toxin - travel thru LMN to CNS where it inactivates inhibitory intraneurons, -- lackjaw (trimus), muscle pain and stiffness and difficulty swallowing

5 month old boy with poor weight gain since birth. he has bulky and greasy stools. what does he most likely suffer from?

abetalipoproteinemia Enterocytes contain clear or foamy cytoplasm that is more prominent at the tips of the villi. occurs due to accumulation of lipids in the absorptive cells of the intestinal epithelium and typical of abetalipoproteinemia, caused by impaired formation of apoliprotein B (apoB) containing lipoprotines Dietary lipids are normally processed in small bowel enterocytes and secreted into chylomircons, endogenously produced lipds are secreted from liver hepatocytes at VLDL. chylomicron and VLDL are synthesized in ER as lipids accumulate around a single apoB molecule ApoB-100- found in VLDL and apoB-48 (truncated with LDL receptor ligand) is in chlyomicrons During synthesis of apoB-containing lipoproteins, microsomal triglyceride transfer protein (MTP) function as a chaperone protein necessary for proper folding of apoB and participate in transfer of lipids to newly formed chylomicrons and VLDL particles abetalipoproteinemia - AR, loss of function muation in MTP gene. -- early in life with malabsorption (abdominal distention, foul smelling stool). labs show low plasma triglyceride and cholesterol levls, and chylomicrons, vldls, apB are entirely absent from th eblood poor lipid absoroption -- def of fat soluble vitamins lead to RBCs with thorny projections - acnthocytes and neurologic abnormalities (progressive ataxia, retinitis pigmentosa).

23 yr old man with fever, headache, confusion. no tobacco or drugs and is monoganous with his wife, CSF shows lymphocytic pleocytosis and PCR is positive for herpesvirus. treated with high dose acyclovir, gets better but on third day serum creantine inc to 3.4 from .9. What could of prevented this finding?

acute increase in creatinine is most likely due to acyclovir nephrotoxicity - 5/10% of ppl who receive the drug intravenously. it is excreted in urine via glomerular filtration and tubular secretion. when gets high, crystallization, crystalluria and renal tubular damage can occur. can be prevented with adequate hydration and reduction in the rate of drug infusion

in summer camp, 4 children between 7 and 9 sent to camp health center with fever, cough, congestion, sore throat and red eyes, PE shows bilateral conjuctivial injection and erythematous oropharynx. Ausculation of one child reveals cracklesin lower lung field. all improve in 7 days with supportive care. waht is the cause of the oubreak?

adenovirus self limiting, all year infection caused the acute onset of fever, cough, congestion, pharyngitis, and conjuctivitis. The pharyngoconjuctival disease can occur in outbreaks among those living in close quarters (camp dorms, military barracks)

3 yr old girl brought to office with leg stiffness. her mother reports that patient is lumsy walker and requires assistance to ambulate. the patieent was born preterm and has delayed developmental skill. PE shows inc knee and ankle reflexes and clonus at the ankles bilaterally. muscle tone of the upper extremities and neck is also inc. MRIs shows periventricular leukomalacia suggestive of cerebral palsy. oral med that reduce the extremity stiffness. What CNS drug effects most like resulted in patient improvement?

agonist activity at GABA receptors. cerebral palsy - heterogenous condition characterized by permanent, nonprogrsive motor dysfunction caused by damage to the developing brain, spastic cerebral palsy - delayed gross motor milestones and spasticity (hypertonia, hyperreflexia) can be due to white matter necrosis (periventricular leukomalacia) which lead sto loss of descending inhibitory control from the UMNs. this results in muscle overactivity leadin to inc ton and hyperreflexia Enhancement of CNS inhibitory NT activity can improve spasticity. GABA is the primary inhibitor NT in the CNS that hald 2 ways - GABA A - fast respoen to GABA - ion gated chloride channel, activation leads to rapid muscle relaction and sedation. enhanced by benzos -GABA B - slower response to GABA becuz it is mediated by G protein coupled receptor that open potassium channles - agonized by baclofen - used for spasticity

13 yr old boy, right knee pain, weeks ago developed mild anterior knee pain that worsen and now cause him to limp. cant play basketball, releived by rest and be reproduced when patient straighten out his right knee while seating in a chair. he has an avulsion fracture affecting a devloping secondary ossification center to due muscle overuse. What structure is involved?

aka traction apophytisis patient has Osgood-Schlatter Disease (OSD) - common cause of knee pain in adolescent athletes, due to overuse of the quads group (rectus femoris, vastus intermedius, vastus medialis, vastus lateralis). Quads - leg extension at the knee and insert into tibial tubercle via the patellar ligament. tubercule forms a secondary ossification center (apophysis) of the tibia, and cartilaginous nature of developing tibual tuberosity in childhood makes i tmore prone to injury OSD - occurs after a growth spurt - due to inc tension in tendons and ligaments caused by rapidly elongating bone. then repetitive quad contraction - results in chronic avulsion of the tibial tubercle. findings: include tenderness, swelling at tibial tubercle and worsen with knee extension ( jumping) imaging shows elevated and fragmented tibial tubercle

Blood supply coming off aorta in lower abdomen? what the external iliac become?

aorta -> common illiac --> internal and external iliac external iliac give off -- inferior epigastric; proximal to the inguinal ligament before the external iliac artery becomes the femoral artery. inferior epigastric run superiorly and medially up the abdomen, and supply lower abdominal all. external iliac give off -> deep circumflex iliac artery - branch lateral - supply blood to lower abdominal wall the external iliac becomes the femoral artery

75 yr old man brought to the ER by paramedics, found to have heavy calcifications of the aortic valve are seen. which of the following most likely preceded the aortic valve changes seen in the patient?

aortic valve calcifications most likely represent dystrophic calcification affecting an aging aortic valve, dystrophic calcification is a hallmark of cell injury and death, occuring in all types of necrosis (coagulative, fat, caseous, liquefactive) in setting of normal calcium levels are seen as fine, gritty, white granules or clumps. on H and E - appear as dark purple, sharpe edged aggregates. deposts that develop lamellated outer layers are described as psmammoma bodiea is thought to be due to endothelial and fibroblast death secondary to chronic hemodynamic stress (accentuated by valvular abnormalties or atherosclerotic inflammation. subsequent release of cellualar degradation products into the valvular interstitium then promote calcificationand thickening of the valve leaflets and annulus. there are benign in elderly (aortic stenosi) but over tiem can lead to outflow obstruction (calcific aortic stenosis)

64 yr old smoker evaluated for nagging right shoulder pain that radiates to the ipsilateral arm, weakness in the right upper extremity, his symptoms start 2 months ago and have worsened progressively. on neuro, patient is alert, oriented, and follow commands. he has partial right sided ptosis with fully intact extraocular movements. pupils are asymmetric in dim light wiht 2 mm on the right and 4 mm on th eleft, both are reactive to light. pupils becomes more symmetric in bright light. the right upper extremity has 3/5 strength and absent deep tendon reflexes. the patients autonomic dysfunction is most likely a result of a lesion involving what?

autonomic ganglia smoking history, upper pain/weakness and ipsilateral ptosis and miosis. -- pancoast tumor -- non-small lung cancer (squamous cell carcinoma, adenocarcinoma) that arise near the super sulcus (the groove produced by the subclavian artery). clinical manifestations are deteremined by the extent of the local spread. compression and invasion of the brachial plexus can cause ipsilateral shoulder pain, upper limb paresthesias, areflexic arm weakness. involvement of the cervival sympathetic ganglia - horners syndome, which is characterized by ipsilateral: - partial ptosis (dropping of upper eyelid), denervation of the sympathetically controlled superior tarsal muscle of the upper eyelid -miosis - constricted pupul - interruption of symp fibres to the dilator pupillae muscle, leads to unopposed parasympathetic influce.. pupil asyemtry more seen in dim light due to inc symp activity exacerbating the defect - anhidrosis - impaired sweating, due to loss of sympthatic innervation of the facial sweat galnds

What is patient centered care?

being responsible to the patients expressed concerns and providing necessary information to assist the patient in making an informed health care decision. the emphasis should be shared decision making, taking into account the patients prferences and avoiding premature judgements.

6 month old girlm adopted from another country, breathes hard and fast esp after crying or feeding, lips turn blue, has a 4/6 harsh cresendo-decrendo murmur best heard at left upper sternal border. Hematocrit is 52, platlet 240k, and leukocytes 11k What is explanation for inc hematocrit?

child has polycythemia - elevation of RBCs that usually result from inc EPO (secondary polycythemia) most common 2ndry cause is chronic hypoxemia. in this patient, failure to thrive, harsh murmur and episodic respiratiory distress and cyanosis (tet spells) --cyanotic congenital heart defect chronic hypoxemia results from R to L shunting and underperfusion of the pulmonary arteries. systolic, cresendo-decresendo murmur at the left upper sternal border - pulmonic stenosis, tetralogy of fallot. due RVOT obstruction, R to L associated with VSD in ToF. Hypoxemia leads to tissue hypoxia in the inner cortex and medullar of kindney -> inc renal production of erythropoietin.

22 yr old woman wER, severe left frontal headache for last 30 min, similar pain everyday for last 3 days, episodes resolve spontaneously after an hr. no meds, PE - restless and in pain, ptosis on left side. What is most suggestive of cluster headache?

cluster headache - a type of trigeminal autonomic cephalagia. rapid onset, severe, unilateral pain, periorbital, frontal or temoral. restless or agitated during often have ipsilateral autonomic syndrome - conjuctival injection and lacrimation - nasal congestion rhinorrhea -ptosis, miosis, anhidrosis last 15-180 min and occur in clusters - 8 times daily at the same time of day over period of several weeks. can involve hypothalamus which regulate circadian rhythm, give oxygen or triptans (sumatriptan); verapamil is used for prevention

When is mesna taken? why?

mesna prevents hemorrhagic cystic caused by nitrogen mustard based chemo agent, such as cyclophosphamide or one of its analogs (ifosfamide). they are metabolixzed in kidney to acrolein, which. is excrete din the urine. it is toxic to uropeithelial cells and cause cell death and necrosis if allowed to be in contact with these cells for longer period of time Mesna (2-mercaptoethanesulfonate) - sulfhydryl compound that binds and inactivates toxic metabolites of the chemotherapeutic agents in the urine.

what is the treatment for NMS?

dantrolene - antagonize ryanodine receptors and inhibit calcium release from the SR or Bromocriptine, a dopamine agonist

54 yr old man with nonsichemic cardiomyopathy, hospitalized fro acute decompensated HF, has dyspena on mild exertion. history of htn and takes multiple meds. bp is 116/70 pulse is 72/min and regular PE - elevated JVP, bibasilar lung crackles, and lower extremity edema. serum creatinine is 1 and serum P is 4.2 Three weeks after starting digoxin - symptomatic relief. What is the initial cellular event triggering this response to new meds?

dec sodium efflux from myocardial cells Digoxin is a positive inotropic agent, symptomatic relief to ppl with acute decompensating heart failure due to LV systolic dysfunction Inc the parasympathatic tone and slow conduction through the AV node, which can help improve cardiac function in patients with rapid ventricular rate directly inhibit the Na/K/ATPase pump, leading to decrease sodium efflux and increase in intracellular sodium levels. the dec. transmembrane sodium gradeint reduces the forward activity of Na/ca excahanger, leading to secondary dec in calcium efflux from the cells. Inc. intracellular ca conc stimulates the binding of ca to troponinc c and subsequent actin-myosin cross bridge formation... improved myocyte contractility and LV systolic function.

29 yr old woman comes to the ER due to fever and headache for the last week. the patient has generalized tonic clonic seizure while being evaluated. labs show low hemoglobin, low platlets, high creatinine high total bilirubin, and normal PT and APTT. what is the underlying cause of her condition?

decreased activity of von willebrand factor cleaving protease Pentad of thrombotic thrombocytopenic purpura 1. severe thrombocytopenia 2. microangiopathic hemolytic anemia (MAHA) - erythrocytes mechanically sheared by microvascular thrombi, leading to intravascular hemolytic anemia. this causes elevated biliruin level and undetectable haptoglobin (haptoglobin binds free hemoglobin in the circulation) but confirmtation of MAHA requires identification of schistocytes (triangle cells, helmet cells) on peripheral blood smear - neurologic manifestation - headache, seizure , renal insuffiency, fever vs DIC will have MAHA and thrombocytopenia but abnormal coagulation --- but TTP have normal coagulation studies cuz factors are not signifcantly consumed. TTP is triggered by the formation of autoantibody inhibitors - ADAMTS-13 - a protease that cleaves ultralarge von willebrand factor multimers in the circulation, reducing their prothrombotic activity. ppl with TTP have low levels of ADAMTS-13, which increases the proportion of ultralarge VWF multimers and leads to aggregation and activation of platlets. plasma exchange which removes the autoantibody inhibitors aganist ADAMTS-13, is generally curative.

57 yr old woman comes to office due to left breast pain associated with fatigue, nausea, and unexplained weight loss. has a 3 cm dominant mass in left breast, is adenocarcinoma - find tumor is estrogen positive and her 2 negative. Patient experienced menopause at age 52 Anastrozole treatment is intiated and lead to substanial dec in size of the primary tumor. What is the best explanation for the therapeutic effect?

decreased androgen aromatization estrogens are made for armomatization of androgens. Aromatase belongs to P450 superfmaily and high expressed in ovarian tissue (in which expression is gonadotropic dependent) Aromatase is expressed in adrenal cortex, subcut fat and breast. in postmenopausal women, follicular atresia leads to reduced granulosa cells and dec ovarian estrogen syn. but ovaries and adrenal glands continue to produce androgens in significant quantities and extraovarian armatase maintains a low level of estrogen in the periphery Estrogen is the main hormone driving the growth and development ER positive malginant breast tumors. Armatase inhibitors - (anastrozole, letrozole, exemestane) reduce teh synthesis of estrogren from androgens, supressing estrogen levels in postmenopausal women and slowing progression of ER positive tumors. less effective in premenopausal women- cuz ovarian aromatase is upregulared substainally in response to gonadotrophins.

how should physician respond to past sexual abuse?

empathy and concern, clearly acknowledge the trauma and communicating a willingness to discuss it when the patient is ready will help strengthen the physician-patient relationship

migraines -

episodic neurological disorder that results in severe, unilateral, throvving headaches often associated with photophobia, phonophoboa, nausea/vomiting. last 4-72 hrs, strong genetic predisposition. women are more often affected than men Migraines are thought to be triggerd by self propagating wave of depol spreading across neurons in the cerebral cortex, resulting in activation and sensitization of trigeminal nerve nocioceptors. people develop focal, reversible neurological symtoms that precede or accompany the headache known as an aura. - can be interpreted as positive - bright spots, noisies, parasthia, movements o negative.- vision loss hearing and sensation loss. aura typically develop progressively over a period of minutes

what does erythema multiforme look like?

erythematous, round papules that evolve into target lesions with dusky central area, a dark red inflammaotry zone surrounded by pale ring, and erythematous halo in lesions periphery. EM presents a cell mediated immune process, with an inflammatory infiltrate predominated by cytotoxic CD8+ lymphocytes. EM is most frequently associated with herpes and mycoplasma due to immune response aganist antigens in the skin. can be seen with sulfonamides, malignancy, collagen vascular disease.

10 yr old boy with difficulty swalloing, during dinner, chicken got stuck in patient mid chest, has had previous sensation of food getting stuck, but never lasted this long. has vomited multiple times, but no change to chicken lol he has history of eczema he is drooling and visibly uncomfortable endoscopy shows multiple stacked, circulate, ring like indentations; linear furrowing and scattered, small whitish papules. What is prob seen on biopsy?

history of solid food dysphagia has an esophagel food impaction - eosioniphilic esophagitis Th2 cell mediated triggerd by food antigen exposure Th2 release IL-5, and Il-13 that stimulate eosinophil recrutiment most common in males with history of atopic conditions (asthma, eczema)., have intermitted solid food dysphagia. can see vomiting reflux and chest and upper abdominal pain. endoscopic - stacked, circular, ringlike indentations; linear furrowing and scattered small whitish papules (eosinphilic microabsesses)

28 yr old man with rash on lower extremity, noticed pruritic papule on dorsum of right foot just prior to returning from a south florida beach 2 days ago. was walking barefoot on the beach but does not recall any trauma. it is now itchy had gotten worse, What si the likely cause?

hookworm infection Serpiginoius, pruritic rash shortly after walking barefoot on the beach, .. hookworm infection. spread when egg containing feces are desposited in shady, warm, moistsand or soil. eggs hatch into larvae and are transmitted when come in direct contact with human skin dermal penetrations - pruritic maculopapular lesion ( ground itch) at site of larval entry (foot, toe web).. spread can form migration, reddish brown, serpiginous tracks Human hook worms - Necator americanus, A duodenale - penetrate BM and spread from dermis to the bloodstream. they rupute into the alveoli and are coughed up and swallowed into small intestine. larvae mature into adult hookworms that feed on blood from duodenal mucosa (iron def anemai) and shed 10k a day Cat and dog hookworms - acylostoma braziliense, a canium - cause dermal eruption in humans but cant penetrate the cutaneous BM and spread to deeper tissue. there larvae do not mature into adult hookworms or spread from human to human

31 yr old woman, gravida 3 para 2, 28 weeks gestation come for prenatal visit. She has chronic htn that was well controlled during pregnancy, previously bp was 120/70 and today is 150/100 and repeat is 152/98, urinarylsis shows +2 protein Transabdominal ultrasound reveal oligohyrdraminos and fetus growth restiction COmpared to normal, what hemodynamic changes of placental vascular resistance, uteroplacental perfusion and umbilical vein oxygen delivery

inc placental vascular resistance dec uteroplacental perfusion dec umbilical vein oxygen delivery Preclampsia -abnormal developmend of placental cytotrophoblats and spiral arteries, which provide blood uspply to fetus and placenta. in healthy preg - cytotrophoblast acid on endoethlial and muscular layers of spiral arteries, change the spiral arteries from small, tortuous vessels to high capacitance, low resistnace vessesl. these changes allow for inc uteroplacental perfusion and preferential supply of blood to the fetus for growth developemnt Preclampia - spiral arterties remain narrow and toruous -- high placental vascular resisance this leads to dec perfusion and so dec umbilical vein oxygen delivery without oxygen, the fetus will show its grwowth -- fetal growth restriction - and shunt blood from the periphery (kidneys) to th ebrain, leaded to dec fetal urine output and oligohydraminos.

What causes a clept lip

maxillary prominence fails to fuse with intermaxillary segment during the firth and sixth week of developemnt

What normally happens to the second brachial cleft? - second pharyngeal groove?

obliteraed in utero, persistence leads to branchial cleft cyst at between the angle of the mandible and scm.

62 yr old man memory impairment and frequent falls, lived alone for 1 year after death of wife, son visits and see poor living conditions, patient is forgetful and did no location of items in his house, where lived for 20 years, gait is unstead and had several falls, he has been "a drinker" patient says he feels fine, PE - bilateral gaze palsy and nystagmus are present. muscle strength and dtrs are normal but gait is ataxic. memory recalls 0 of 3 objects after 3 minutes, Where is the lesion? dx?

oculomotor dysfucntion (nystagmus, opthalmoplegia), ataxia, encephalopathy (confusion, anterograde amnesion) ==wernicke encephalophy - complication of thiamine deficiency thiamine is cofactor for glucose metabolsim, def results in brains inability to use glucose and turn into energy, leading to neuronal damage and necrosis. areas of brain with high metabolic demand are suseptible - mammilary bodies - focal hemorrhage and atrophy on imagine. others common - thalamus, periaqueductal gray substance, locus caeruleus. Chornic effects of thiamine def -- Korsakoff -- anterograde and retrograde amensia, pathy, lack of insight and confabulations. attenion, socail behavior and long term memory are relatively preseverd.

researching a novel alkylating chemotherapeutic agent aganist glioblastoma mulitforme. They find malignant cells with methylation of the promoter region - O-methylguanine-DNA- methyltransferase (MGMT) gene are more susceptible to this drug than cells without methylation. What is the most likely function of the protein encoded by the gene?

oncogenesis an be mediated by altered expression of unmutated genes: - histone modificaiton - chromatin organized into nucleosomes, - segment of wrapped dna around 8 histones. modification of histones via acetylation, phosphorylation or methylation can alter the availability of DNA for transcription, leading to inc or dec gene expression. Histone modifcaiton - allow tumors to increase prosurvival gene expression and reduce cell cycle arrest/apoptosis gene expression - Transcription factor expression - TF activated by cell surface ligand binding or phosphorylation. Activated TF travel to nucleus and bind to promter/enhancer of specific gene -> alter RNA polymerase binding -> gene expression Tumors overexpress surface receptors (HER2) that generate prosurvival TF and underexpress surface receptors that generate cell cycle arrest/apoptotic signals -CpG modificaitons - Promoter region contain 200-2k bp that contain cytosine followed by guanosine. methylation of CpG region silence the adjacent gene, neoplasms often methylate CpG promoter region adjacent to genes that slow growth In glioblastomas - they methylate the CpG region adjacent to O-methylguanine-DNA methytransferase (MGMT) gene, which generate a protein that repairs damaged DNA. this makes a more persmissive environment for DNA mutaiton to drive cancer growth, it also makes the cell more susceptible to alkyalating chemotherapy (temozolomide) - since alkylated agents cause DNA damage that cant be repaired with MGMT.

20 yr old woman with 6 hrs of right lower quadrant pain , suddenly and intense and constant, unable to eat or drink today due to nausea and frequent vomiting. has had 2 sexual partenrs and treated for chlamydia, takes ibuprofen for period pain, has a 6 cm right ovarian cyst noted last year, last period was 3 weeks ago, 99F, 110/80, 104/min. tenderness to deep palpitation in RLQ. negative preg. leukocyte count is 8k What is the diagnosis?

ovarian torsion, emergency people in reproductive age. partial or complete rotation of the ovary around the infundibulopelvic (suspensory ligament of the ovary) and uteroovarian ligaments, which can affect ovarian blood supply cuz ovarian vessesl travels in the infundibulopelvic ligament. right sided torsion is more common cuz the the uteroovarian ligament is longer cuz the rectosigmoid colon takes up space around the left ovary (leaving less room for movement) risk factors - pregnancy, ovulation induction, ovarian masses >5cm symp: sudden onset lower abdominal pain, nausea and vomiting. PE shows unilateral abdominal or pelvic tenderness. Initial evalution - cbc and preg to rule out ectopic pregnancy.

what is small intestinal bacterial overgrowth associated with?

overproduction of vitamin k and folate by enteric bacteria, associated with anusea, bloating, abdominal discomfort and malabsorption. gastric byass surgery can cause this. due excess growth in the blind ended gastroduodenal segment. most often leads to deficiency in b12, a, d, e, and iron but inc poduction of folic acid and vitamin k

54 yr old with history of hep C infection, vomiting bright red blood, admitted to hospital, disoriented and cannoted identify the month or current location. PE - abdominal distention and gynecomastia. Repetitive flicking motions of the hands when patient outstretch his arm and dorsiflex his wrist. What is contributing to altered mental status?

patient has cirrhosis - hep C infection, abdominal distenstion, gynecomastia - hepatic encephalopgy with GI bleed. reversible decline in neurologic function that occur due to failure of liver to metabolize waste products such as ammonia. It is normally produce din GI tract as a result of enterocytic catabolism of glutamine and colonic bacterial catabolsim of dietary protein. GI bleed - inc nitrogen delivery to the gut in the form of hemoglobin, which is then converted into ammonia and absorbed into the blood stream. The ammonia then enter the liver thru portal vein and is detoxified to urea. in chornic liver failure, hepatocyte dysfunction and shunting of blood thru portosytemic collatores imapir the liver ability to detox .. lead to accumulation of ammonia, and other neurotoxins, causing altered AA transport across BBB, impaired NT metabolism, and dec cerebral glucose metabolsim This leads to increased inhibitory neurotransmission (GABA) and impaired excitary NT release (glutamate, catecholamines) To lower blood ammonia levels - give lactulose - bacterial action of lactulose leads to acidification of colonic contents, which converts absorbal ammonia to nonabsorable ammonium ions, trapping in stool and inc fecal nitrogen excretion.

62 ye old man with persistent cough and exertional dyspnea has progressed over the past year. no difficulty with daily activites, no signifcant medical history, smoked for 10 yrs, quit 25 years ago. patients works as an investment banker and does not use alochol or illict drugs. CT scan shows idopathic pulmonary fibrosis. What changes would be seen in type 1, type 2 pneumocytes, bm, and fibroblasts?

patients chronic progressive dyspnea, noproductive cough, digital clubbing and inspiratory crackles are concerning for interstial lung disease. CT show peripheral reticular infiltrates (thickened, linear interstitial markings) with subpleural honeycoming (multiple cystic spaces with irregularly thickened walls), suggestive of idiopathic pulmonary fibrosis histo - fibroblast proliferation and dense collagen deposition intermixed with unaffected lung (usual interstial pneumonia pattern). Pathogenesis - repetitive epithelial injury (smoking, acid reflux) following by: 1. repetitive lung microinjuries result in loss of type 1 pneuomocytes, which compose of 95% of gas exahnge alveolar surface area. 2. Type 1 are incapable of replication. normal repair requires the proliferation of type 2 pneumocytes, with differentiation to type 1 to reestablish the alveolar epithelial lining. 3. IPF, type 2 pneumocytes undergo reactive hyperplasia but fail to differentiate into type 1 cells becuz of dysfunctional cell fate pathways (wnt/transforming growth factor-beta) and abnormalities of the underlying basement membrane. 4. impaired re-epithelialization causes lung fibroblasts to undergo focal proliferation and begin secreting excessive amounts of collagen, leading to interstital fibrosis 5. fibrosis exerts radial traction on teh distal airways, leading to dilation of the terminal bronchioles and producing the honeycomb appearance characteristic of IPF.

70 yr old man, left sided weakness and slurred speech upon awaking 30 min ago, was asymptomatic when went to bed, former smoker with 30 yr pack, PE shows right gaze preference, left lower facial droop, hemiplegia and hemisensory loss on the left. CT - early infarction in the right upper MCA with no acute hemorrage. Patient is hospitalized for futher management. hours later becomes obtunded with elevated ICP. repeat CT shows edema in the region of the acute infarction causing mass effect What is the primary contributer to pathogenesis of patient raised ICP?

right hemispheric ischemic stroke - with altered mental status and inc ICP secondary to cerebral edema inc ICP can cause progressive neurologic impairment through direct pressure induced cell injury or mechanical damage due to brain herniation irreversible ischemic neural and glialc cell injury intitate a sequence of chemical cahnges that promote edema: 1. cytotoxic (ionic) edema begins hours after ichemic injury due to dec. ATP. failure of ATP dependent ion pumps - combined with release of exictatory amino acids (glutamate) leads to accumulation of intracellular Na and water in neural and glial cells despite intact BBB 2. vasogenic edema - 24-48hrs later, when the release of inflammatory mediators disrupt the tight junctions of BBB, allowing proteins (albumin) and water to enter the interstitial space. Vasogenic pahse can cause persisent cerebral edema for weeks after initial injury v

21 yr old man at ER after suffereing an injury during football game. He was falling to the ground when he was struck forcefully from behind by the helmet of an opposing player. the patient was able to ambulate after the injury but since has had severe pain worsened by deep breaths. his bp is 110/65, pulse is 110, resp 16. there is bruising and tenderness over the left posterior chest wall. there is normal range of motion and no midline tenderness. Gait and lower extremity neuro exam are normal. Image reveal a fracture of the 12th rib. What sturcute is lacerated by the fracture?

the first 7 ribs are true ribs, becuz their costal cartilage directly to the sternum. the cartilage of the lower 5 pairs does not, they are considered "false" ribs. of these 8-10 attach to the costal cartilage of the upper ribs. the 11 and 12 are "floating ribs" they are not bound to the anterior rib cage by cartilage. the 12th rib, overlies the parietal pleura medially and the kidney laterally. for this reason, the distal tip of the 12th rib can be displaced into the retroperitoneum when fractured, lacerating the left kidney

What shows constrictive pericarditis?

thickening and calcification of the pericardium suggestive of constrictive pericarditis, normally 1-2mm thick, can range in thickness frm 4-20 in constrictive pericarditis. have slowly progressive dyspnea, chronic edema, ascites. rapid y descent - becomes deeper and steepr during inspiration. causes - radiation therapy to the chest, cardiac surgery, tuberculosis

What is restless leg syndrome? what meds can help?

uncomfortable sensation in the legs accompanied by an urge to move then, worse with inactivity and at night and relieved by movement. Dopamine agonists (pramipexole, ropinirole) are preferred therapy for persisent symptoms

what is expected with superior gluteal nerve injury?

weakness of gluteal medius and gluteal minimus muscles will cause the pelvis to sag toward the UNAFFECTED (contralateral) side when the patient stands on the affected side (+ trendelenburg sign) when walking, the lean toward the AFFECTED (ipsilateal side) to compensate for hip drop (gluteus medius lurch)