More STEP

Recognize *fibroadenoma* histology

= 15-34 yo = benign-appearing cellular or *myxoid stroma* = encircles epithelium-lined glandular & cystic spaces - compress & distort surrounding glandular epithelium - as women age, epithelium atrophies & stroma becomes more hyalinized

Recognize ghrelin at *consumption of a meal*

= peak of graph = ghrein makes your stomach GROWL - subsequently decreases post-consumption

33 yo woman has had weakness of left lower two thirds of face for past 2 months. What labeled region in the normal brain shown is the most likely site of the lesion causing this symptom?

= precentral gyrus / lower motor cortex

Attack rate

= ratio of number of ppl who contract an illness divided by number of people at risk of contracting illness

Outbreak of infection with seasonal influenza A strain is reported in small community. Strain is similar to one that circulated in the preceding year. Approximately 70% of adult population in that community remains uninfected, despite prolonged & repeated exposure to ill contacts. What is the most important host factor in preventing influenza infection in these subjects?

*Antibodies against hemagglutinin* - humoral response with Abs directed against hemagglutinin = most important source of protection = can neutralize virus & block its binding to host cells Mutation in viral-encoded envelope glycoprotein can dramatically affect range of host cells that virus can attack to or infect

45 yo man comes to office for follow-up. He was diagnosed with focal epilepsy 2 years ago & has been treated with several antiepileptic meds. Over last 6 months, his seizure frequency has increased despite compliance with med therapy. Neuro exam & brain imaging are unremarkable. The patient is started on new antiepileptic med that selectively blocks voltage-gated calcium channels. This med most likely affects what steps on neurotransmission?

*Fusion & release of NT vesicles* When AP reaches axon terminal, voltage-gated calcium channels open & allow influx of calcium = essential for fusion & release of NT vesicles into synaptic cleft Gabapentin - inhibits presynaptic voltage-gated calcium channels

69 yo woman comes to physician because she has had weakness of her left leg since awakening that morning. Physical exam shows weakness of extremity. Babinski sign is present on left. Sensory testing shows decreased somatic sensation in left foot, agraphesthesia, on plantar surfaces of toes, & decreased position sense in toes. An MRI of brain shows an edematous area in cerebral cortex of right hemisphere. The most likely cause of this condition is a lesion located at what labeled area in the photograph of normal brain shown?

*G* - symptoms restricted to lower extremity only = medial surface - patient having UMN signs as well as sensory deficits = anterior (motor) or posterior (sensory) to central sulcus of ronaldo - G since Babinski sign positive Around G = both precentral and postcentral gyrus - patient's symptoms due to primary somatosensory & primary motor cortex affected by lesion

Examination of tissue obtained on biopsy of a neoplasm on the scalp of a 45-year-old man shows early invasive squamous cell carcinoma. The site of incision for the biopsy is not sutured. One week later, the mass is widely excised. In the excised specimen, the biopsy site is most likely to show what?

*Granulation tissue* Wound healing: Proliferative (day 3 - weeks after wound) - *fibroblasts*, myofibroblasts, endothelial cells, keratinocytes, macrophages - deposition of *granulation tissue* & type III collagen, angiogenesis, epithelial cell proliferation, dissolution of clot, wound contraction (mediated by myofibroblasts) - delayed wound healing in vitamin C deficiency & copper deficiency

9 month old girl brought to ED after 2 minute generalized seizure. Patient has had fever for past 12 hours and has been very fussy. She takes no meds and has no allergies. Her temp is 39.4 C (103 F). Exam shows no abnormalities, and the patient is discharged home. Three days later, she is afebrile but develops a maculopapular rash on her trunk. Infection with what is the most likely cause of this patient's condition?

*Human herpesvirus 6* Roseola infantum = via HHV-6 = febrile seizures = high fever for 3-5 days followed by erythematous maculopapular rash = usually starts on trunk & spreads to face & extremities - diagnosis based on clinical presentation

57 yo man comes to office due to unrefreshing sleep. He feels tired during day & occasionally has to nap during his lunch hours. According to his wife, patient snores loudly during sleep & frequently gasps for breath. He also has severe claustrophobia. Past med history is significant for HT. Patient takes no sedative meds & is a lifetime nonsmoker. BP is 156/94 mmHg & BMI is 30 kg/m^2. Physical exam is significant for bulky tongue & crowded, narrow oropharynx. Electrical stimulation of what nerves may improve pathophysiological cause of this patient's symptoms?

*Hypoglossal* --> via implantable nerve stimulator that causes tongue to move forward slightly = increased anteroposterior diameter of airway Obstructive sleep apnea (OSA) = recurrent upper airway collapse during sleep Neuromuscular weakness - apnear occur only during sleep = time of muscle relaxation

16 yo girl comes to office due to pelvic & crampy lower abdominal pain that seems to recur at beginning of each month & resolves after a day or two. She thinks the pain began approximately 6 months ago, & it is worsening significantly each month. Patient has never had menstrual period. She & her boyfriend have not had any form of sexual intercourse, including digital, oral, vaginal, or anal. Patient's weight, height, & BMI are average for age & sex, & she has fully developed secondary sexual characteristics. Exam reveals palpable mass anterior to rectum. Serum beta-hCG is negative. What is the most likely diagnosis?

*Imperforate hymen* - obstructive lesion - incomplete degeneration of central portion of fibrous tissue band connecting walls of vagina - at birth, vaginal secretions stimulated by mom's estrogen = mucocolpos (accumulation of mucus in vaginal wall) = bulging introitus --> undiagnosed? = reabsorbed by --> child = symptomatic until menarche - primary amenorrhea + normal secondary sex characteristics with cyclic abdominal or pelvic pain via accumulation of menstrual blood in vagina & uterus (hematocolpos)

In immunocompromised patients, the case definition of a positive PPD skin test was changed from 10 mm of induration to 5 mm of induration. This change has what effects on incidence and prevalence of a positive PPD skin test? Incidence = Prevalence =

*Incidence = increased* *Prevalence = increased*

In experiment, cultured fibroblasts are mechanically lysed, & membrane lipiids & cellular proteins are chemically removed to isolate nucleic acids. Cellular extract containing purified nucleic acids is incubated along with short sequences of repeated deoxythymidine residues fixed to latex beads. The solution is washed several times to remove unbound molecules. What types of nucleic acids is most likely to bind strongest to latex beads in this experiment?

*Mature mRNA* Poly-A tail on mature mRNA would most likely bind to latex beads because adenine residues in tail would form complementary base pairs with repeated deoxythymine residues fixed to beads

68 yo male presents to office complaining of urgency, frequency, weak urinary stream, & straining on micturition. These symptoms have been present for past few years, but have gradually become more severe. He also notes noturia, as well as oliguria alternating with polyuria. Patient's kidneys are most likely to demonstrate:

*Parenchymal pressure atrophy* Urinary retention --> increased pressure in urinary tract = morphologic changes - bladder wall hypertrophies = increased contractile force - progression --> ureter, renal pelvis, calyces dilate & deform = hydronephrosis - *renal parenchyma ultimately becomes atrophic & scarred via reflux of urine & damage of renal tissue*

What is abnormal in patients with Hemophilia?

*Partial thromboplastin time* - male sex + fam history of hemarthrosis - isolated prolongation of partial thromboplastin time via defects in intrinsic coagulation pathway - intramuscular hemorrhage, hemarthrosis, prolonged or delayed bleeding after surgical procedures

6 yo immigrant from Eastern Europe brought to ED by his parents after they found him having difficulty breathing. Child has fever & has not been eating or drinking for last several hours. Head & neck exam reveals neck swelling, palatal paralysis, & a gray pharyngeal exudate. Parents are unable to provide info regarding child's vaccination history. What interventions is most likely to improve this patients prognosis?

*Passive immunization* C diphtheria - toxin ribosylates & deactivates elongation factor-2 --> inhibits human protein synthesis *Treatment* - diphtheria antitoxin - penicillin or erythromycin - *DPT vaccine* Antitoxin = *passive immunization* = transfer of pre-existing neutralizing Abs

58 yo man comes to physician because he has noticed blood in his urine over last few days. During work-up of his hematuria, he undergoes an abdominal CT scan that reveals a right-sided renal mass. Biopsy of the mass demonstrates rounded & polygonal cells with abdunant clear cytoplasm. The patient's lesion most likely originated from what portions of the kidney?

*Proximal renal tubules* RCC = 70% of all kidney tumors Clear cell carcinoma = most common subtype of RCC = cuboidal or polygonal cells = golden-yellow on macroscopic exam via high glycogen & lipid content = originate from epithelium of proximal renal tubules = 60-70 yo - risk factors = smoking & obesity

54 yo missionary traveling alone in remote region of Southern Asia becomes lost. After several days, he arrives at a small village. However, he has gone 24 hours without food or water, & his urine osmolarity is 1150 mOsm/L. The majority of total amount of water filtered by this individual's glomeruli is reabsorbed in what portion of the nephron?

*Proximal tubule* - reabsorbs >60% of water filtered by glomeruli, regardless of patient's hydration status

What is normal in a patient with pancreatitis, who developed Acute respiratory distress syndrome (ARDS)?

*Pulmonary capillary wedge pressure (6-12)* ARDs - injury to pulmonary microvascular endothelium & alveolar epithelium - increased pulmonary capillary permeability - leaky alveocapillary membrane - *noncardiogenic pulmonary edema with normal PCWP* - decreased lung compliance - increased work of breathing = interstitial & alveolar edema = exduate formation

18 yo woman referred to cardiologist after heart murmur discovered during routine checkup. Patient is healthy & has no symptoms. Past medical history is unremarkable. She runs daily & wants to start actively training for a half marathon. She is concerned that the murmur is a sign of heart disease & would prevent her from pursuing her athletic activities. She has no family history of sudden cardiac death. Auscultation reveals midsystolic click that is followed by short late-systolic murmur at cardiac apex. The murmur disappears with squatting. This patient's condition is most likely related to an abnormality involving what tissues?

*Connective tissue* Mitral Valve Prolapse = midsystolic click followed by mid- to late systolic murmur at cardiac apex = disappears with squatting = sporadic disorder mostly = myxomatous degeneration (pathologic deterioration of CT) = proliferation of spongiosa of valve leaflets, fragmentation of elastic fibers with increase in mucopolysaccharide, & type III collagen deposits Squatting --> increases venous return & LV volume = decreased degree of MVP = delay in onset of click during systole; systolic murmur typically becomes shorter or disappears

24 yo woman presents to her physician with weakness in flexing the hip joint & extending the knee joint. What muscle is most likely involved in this scenario?

*Rectus femoris* - flexes thigh & extends leg

20 yo patient cannot flex & medially rotate thigh while running & climbing. What muscles is most likely damaged?

*Tensor fascia latae* - flexes & medially rotates thigh

Newborn delivered at term to 40-year-old primigravid woman. Chronic villus sampling at 15 weeks' gestation was done and results of chromosomal analysis showed a male fetus. Physical exam shows female external genitalia. Further tests are most likely to determine that his child has a mutation preventing responses to what hormones?

*Testosterone* Androgen Insensitivity Syndrome - defect in androgen receptor - normal appearing female (46, XY DSD) - female external genitalia - increased testosterone, estrogen, LH - lumps in labia majora = testes

46 yo female who presented to ER with severe headache is diagnosed with subarachnoid hemorrhage on non-contrast CT scan. Few days after admission, she develops weakness in her right arm and leg. Repeat CT scan shows no significant change. The new symptoms are most likely caused by what?

*Vasospasm* Subarachnod hemorrhage: if patient survives... secondary arterial vasospasm may occur - vessels surrounding ruptured aneurysm - cerebral ischemia = new-onset confusion &/or focal neuro deficit 4-12 days after intial insult - related to impaired brain autoregulation - transcranial color Doppler needed - nimodipine = prevents vasospasm

Patient experiences paralysis of muscle that originates from femur & contributes directly to stability of knee joint. What muscles is involved?

*Vastus lateralis* - arises from femus

M pneumoniae requires what to grow?

*cholesterol supplementation* - also grows on Eaton agar

4 yo Caucasian boy evaluated for difficulty walking. Past medical history includes frequent respiratory infections. Cultured cells from this patient demonstrate high rate of radiation-induced genetic mutation. This patient is most likely to experience what?

*Cerebellar atrophy* Ataxia-telangiectasia = AR = ataxia that occurs in first years of life - oculocutaneous telangiectasia = another manifestation but is usually delayed - severe immunodeficiency with repeated sinopulmonary infections = risk of cancer via inefficient DNA repair = defective *DNA-repair genes* = hypersensitive to ionizing radiation

Recognize h pylori in gastric pits on silver stain, which causes *Peptic Ulcer Disease* Case "45 yo man comes to physician because of gradually worsening heartburn over past 3 months. Physical exam is unremarkable. Endoscopic exam of stomach shows thickened, nodular mucosa with no discrete ulcerations. A representative Steiner silver-stained gastric biopsy (400X) is shown. The abnormality shown is most commonly associated with the development of what disease?"

- event though patient maybe doesn't have PUD currently, PUD is still answer because it is abnormally associated with H pylori

Recognize *ADPKD CT*, which is, of course, Autosomal Dominant

- positive fam history & numerous kidney & liver cysts seen by 3rd-4th decade

Recognize pressure-loop diagram of *normal saline infusion*

- rightward extension of ventricular filling portion = larger than normal left ventricular end-diastolic volume = *increased ventricular preload* (fluid overload: renal failure, CHF) or after IV fluids

Mechanism of left ventricular dilated cardiomyopathy

*decreased ventricular contraction force*

An investigator does an experiment in which the third pharyngeal pouches are prevented from forming in a mouse embryo. As a result, what organs will fail to develop?

*Thymus* 3rd branchial pouches = thymus + inferior parathyroids

Patient experiences weakness in dorsiflexing & inverting foot. What muscles is damaged?

*Tibialis anterior* - can dorsiflex & invert foot

34 yo Asian female is hospitalized with progressive exertional dyspnea, lower extremity & cough. She also describes frequent nocturnal episodes of breathlessness & recent hoarseness. She does not use tobacco, alcohol or drugs. Auscultation reveals loud first & second heart sounds & a mild-diastolic rumble best heard at cardiac apex. This patient's hoarseness is most likely caused by:

*nerve impingement* - left recurrent laryngeal nerve may be compressed to point of neurapraxia = failure of nerve conduction via blunt injury = via enlargement of left atrium Mitral stenosis = left atrial dilatation --> impinges left recurrent laryngeal nerve (Ortner syndrome) Recurrent laryngeal nerve = all intrinsic muscle of larynx except cricothyroid muscle

Small cell carcinomas stain for

*neural cell adhesion molecule (NCAM) / CD56* neuron-specific enolase chromogranin synaptophysin

65 yo woman undergoes surgical repair of aneurysm of right internal carotid artery in cavernous sinus. Three days later, physical exam shows that right pupil is larger than left pupil. There is also weakness with movement of eye. Diagram of a coronal section through middle cranial fossa, including cavernous sinus & associated structures, is shown. What labeled nerve is most likely damaged in this patient?

*oculomotor nerve*

Epithelial of ovary

*simple cuboidal* (germinal) - rapidly proliferates to repair ovulatory surface defects

Epithelial lining of palatine tonsil derived from

2nd branchial pouch

Superior parathyroids derived from

4th branchial pouch

Handgrip increases what murmurs?

AR MR *VSD* - increased LV & aortic pressure - increased afterload

12 yo boy swimming in mountain stream. Immersed up to his neck in 60 F water for 20 minutes. What sets of physiologic changes is most likely to occur in this boy? Central Blood Volume = ADH (vasopressin) = Atrial Natriuretic Peptide =

Central Blood Volume = increased ADH (vasopressin) = decreased Atrial Natriuretic Peptide = increased Immersed in cold water... = peripheral vasoconstriction --> increased central body volume --> increased volume in heart --> ANP increases --> ADH decreases to decrease volume

Savage behavior and obesity from stimulation of this nucleus.

Dorsomedial nucleus - from destruction would be ventromedial

CNS lymphomas are universally associated with

EBV - positive for B-cell markers = CD20 & CD79a - immunosuppressed patients, like in AIDS - high-grade = poor prognosis

Recognize acute allergic contact dermatitis, which will = skin biopsy of *spongiosis* "53 yo woman comes to clinic due to skin rash. For last 3 weeks she has had pruritic rash of worsening severity involving posterir thighs. Patient recently began exercise program to lose weight & has been applying topical analgesic cream to her thighs & buttocks after her workouts. On physical exam, there is erythematous rash with blisters, ulcers, & weeping drainage involving posterior thighs bilaterally"

Eczemtaous dermatitis / eczema = erythematous, papulovesicular, weeping lesions Acute allergic contact dermatitis (ACD) = type IV (delayed) HS reaction to antigen on skin surface - Ags taken up be Ag-presenting Langerhans cells & presented to CD4+ T cells in regional lymph nodes Spongiosis = accumulation of edema fluid in intercellular spaces of epidermis

Recognize the kozak sequence, which helps *initiate translation* at methionine start codon (AUG)

Eukaryotic translation initiation - requires assembly of ribosomal subunits (60S & 40S), mRNA, initiation factors, initiator tRNA charged with methionine, guanosine-5'-triphosphate (GTP) - 40S initially binds to 5' cap of mRNA & scans for methionine start codon (AUG) - when start codon is positioned near beginning of mRNA & is surrounded by Kozak consensus sequence, it = initiator of translation Kozak consensus sequence = analogous to Shine-Dalgarno sequence in E coli = *(ggc)gccRccAUGG* = R is either A or G

Segmental demyelination & endoneural inflammatory infiltrate seen on light miscroscopy of peripheral nerves is characteristic of

Guillain-Barre syndrome - ascending muscle weakness - after resp or GI infection - Camp bacter

Recognize *inferior vena cava ct*, which *is formed by union of common iliac veins*

IVC - formed by union of right & left common iliac veins at level of L4-L5 - drains into right atrium from lower extremities, portal system, & abdominal & pelvic viscera

idiopathic membranous nephropathy is associated with

IgG4 Abs to phospholipase A2 receptor

heartsound

Left ventricular hypertrophy - *S4* - extra low frequency heart sound at end of diastole just before S1 - older adults via age-related decrease in left ventricular compliance

Recognize *perforated viscus* case: "A 19-year-old man comes to the emergency department because of increasingly severe shoulder and abdomen pain for 3 days. His temp is 39C. Physical exam shows signs of acute peritonitis. Abdominal xray is shown. Which of the following is the most likely cause of this patient's current condition?"

Perforated viscus = crescent shape sub-diaphragmatic gas shadow on x-ray --> irritation to diaphragm --> referred pain to shoulder & intraabdominal pain

Characteristic positive test result of Pulmonary embolism with ventilation/perfusion scanning.

Perfusion defect without Ventilation defect - CT angiography = diagnostic test of choice - elevated creatinine, contrast allergy = no CT angiography = ventilation/perfusion scan instead

Tumors that are universally S-100 positive

Schwannomas Melanoma - neural crest origin

Interrupting disease process before symptoms develop

Secondary prevention - ex. looking for disease that may be present but asymptomatic in patients receiving med care (age- & gender-appropriate screening - community screening = analogous intervention at community level

Enhances platelet aggregation

TXA2

Recognize xanthelasma, which is associated with *Primary biliary cirrhosis*

Xanthelasma = lipid-laden macrophages = eyelid = associated with primary or secondary hyperlipidemia = chronic cholestatic processes = obstructive biliary lesions & primary biliary cirrhosis

First-line treatment for gonorrhea

dual therapy with ceftriazone *& azithromycin* - concerns about resistance & chlamydia co-infection

Epithelial of cervix

ectocervix = stratifies squamous non-keratinized endocervix = simple columnar

What could exacerbate pre-existing thiamine deficiency in an alcoholic?

influsion of *glucose* without thiamine

Patient that presents with acute-onset chest pain & dyspnea & an abnormal V/Q scan consistent with likely...

pulmonary embolism (PE) - pleuritic chest pain, shortness of breath, tachycardia, tachypnea, hypotension

Mantle cell lymphoma is a B-cell malignancy associated with

t(11;14) - translocation = activation of cyclin D gene

Serum cholesterol concentrations are measured as part of a community study. Mean and standard deviation are given for women by age group: Age (years) ~ Cholesterol (mg/dL) 45-49 ~ 229 +/- 47 50-54 ~ 246 +/- 50 55-59 ~ 255 +/- 48 60-62 ~ 244 +/- 36 Assuming serum cholesterol concentrations follow a normal (gaussian) distribution, what is the probability that a woman between ages of 50 and 54 years has a serum cholesterol greater than 296 mg/dL?

*16%*

What best estimates intrapleural pressure at point on graph marked by red dot (*Functional Residual Capacity (FRC)*

*-5 cm H2O* - net combined compliance = blue curve - alveolar transmural pressure = always positive = perpetual collapsin force on lungs = why curve marked "lung" always has positive value - positive alveolar transmural pressure & negative chest wall transmural pressure oppose one another equally at FRC = airway pressure of 0 --> at FRC, airway pressure is 0 and there is no tendency for air to flow either into or out of lungs At FRC... - tendencies of chest wall to expand & lung to collapse oppose one another = negative intrapleural pressure o -5 cm H2O - during inspiration, intrapleural pressure decreases to average of -7.5 cm H2O = induces slightly negative alveolar pressure that draws air into lungs

Investigators at center are designing randomized control trial to test hypothesis that drug B will decrease mortality associated with acute ST-elevation MI compared to standard of care. To ensure that investigators will not miss a difference between drug B & standard of care (if a difference truly exists), what would they want to maximize?

*1 - beta* Statistical power = (1 - beta) = represents study's ability to detect difference when one exists = probability of rejecting hypothesis when it is truly false = probability of finding a true relationship = depends on sample size & difference in outcome between groups being tested = typically set at 80%

35 yo man comes to physician to discuss donating a kidney to his 39 yo sister who has type 1 diabetes mellitus and chronic renal failure. He has not history of major medical illness, & physical exam shows no abnormalities. What best describes the likelihood the this donor's human leukocyte antigen type will match that of his sister?

*1:4* - you inherit one allele from each parent = 4 different combinations

54 yo man has aneurysm in distal portion of his abdominal aorta. Estimated cross-sectional area of aneurysm is 2 cm^2 and mean velocity of blood flow through aneurysm is 20 cm/sec. What best represents flow rate (in L/min) through aneurysm?

*2.4* Q = AV = 2 cm^2 x 20 cm/sec = 2 cm^2 x 20 cm/sec x 60 sec/min = 2,400 cm^3/min = 2.4 L/min

acute pyelonephritis

- neutrophils infiltrate renal interstitium - fever, flank pain (costovertebral angle tenderness), nausea/vomiting

Recognize *sideroblastic anemia*, why can be associated with *decreased delta-aminolevulinate synthase*

- patient with latent TB can have sideroblastic anemia due to isoniazid use Sideroblastic anemia = diagnosed by bone marrow exam with Prussian blue stain = X-linked sideroblastic anemia (via delta-aminolevulinate synthase mutation), myelodysplastic syndrome, alcohol abuse, copper deficiency, certain meds (isoniazid, chloramphenicol, linezolid) Isoniazid = inhibits pyridoxine phosphokinase, which normally converts pyridoxine/vitamin B6 to active form/pyridoxal 5' phosphate Pyridoxal 5' phosphate = cofactor for delta-ALA synthase = rate-limiting step in heme synthesis - iron is transported to developing erythrocytes that cannot form heme --> granules accumulate circumferentially around nucleus = ring sideroblasts

Recognize *renal artery stenosis ct*

- right = shrunken, atrophic kidney Risk factors for atherosclerosis = advanced age, HT, hyperlipidemia, smoking Chronic abdominal pain that is postprandial (after eating) accompanied by weight loss = intestinal ischemia --> renal artery stenosis Marked unilateral kidney atrophy = renal artery stenosis - elderly ind.s via atherosclerotic changes in arterial intima or women of childbearing age via fibromuscular dysplasia

Recognize *pulmonary arterial hypertension* heart Case: "32 yo woman comes to ED with lightheadedness & shortness of breath, which started while shopping at supermarket. During last 6 months, she had increasing shortness of breath and had to adjust her daily activities. Patient has no other medical problems. After initial assessment, patient reports she feels "fine," refuses further evaluation, & insists on being discharged. She dies a month later."

- thickening of right ventricular free wall compared to left ventricle (showed better in other image) Severe right ventricular hypertrophy in young woman with progressive dyspnea + sudden death = pulmonary arterial hypertension (PAH) - women ages 20-40 - intimal hyperplasia & fibrosis, medial hypertrophy, formation of capillary tufts Suspect pulmonary hypertension in patients ... - young & otherwise healthy + fatigue + progressive dyspnea + atypical chest pain + unexplained syncope

Recognize *junctional nevi*

= aggregates of nevus cells limited to dermoepidermal junction = flat, black- to brown-pigmented macules with darker coloration in periphery and preserved skin markings

60 yo man with 20 year history of HT comes to physician because of shortness of breath and fatigue for 3 months. Shortness of breath is exacerbated by climbing stairs. His pulse is 80/min, & BP is 100/70 mmHg. Physical exam shows peripheral cyanosis. Crackles are heard bilaterally on auscultation of chest. Cardiac exam shows S3. There is pitting ankle edema. What is the most likely set of CO and CVP findings in this patient? CO = CVP =

CO = decreased CVP = increased

Be able to recognize recording of *mitral regurgitation*

Murmur = blowing = holosystolic = radiates to axilla "23 year old female from Cambodia complains of exertional dyspnea. She has occasional dry cough. She had bilateral knee swelling as child. Cardiac auscultation over apex can be heard..." Via rheumatic heart disease - still in other parts of world

Recognize saddle pulmonary embolus ct, which is contributed to by *hypercoagulability* Case: "72 yo man. Chest tightness & dyspnea, which started several hours ago at fam dinner. Has never experienced similar symptoms. Patient's med problems include HT, hyperlipidemia, type 2 DM, prostate cancer. He has moked pack of cigarettes daily for 30 years & stopped smoking 10 years ago."

Saddle pulmonary embolus - chest tightness & dyspnea + chest CT scan (stradding bifurcation of main pulmonary artery) History of prostate cancer, smoking, and age = high risk of developing *venous thromboembolism* (DVT) PE via Virchow triad - endothelial injury - venous stasis - *hypercoagulable state* (via cancer)

Treatment for t(15;17)

Vitamin A (retinol) / All-trans retinoic acid Acute promyelocytic leukemia (APML) = M3 variant of AML - PML/RARA = abnormal promyelocytes & Auer rods = anemia, thrombocytopenia, neutropenia = DIC DIC = thrombocytopenia, elevated D-dimer, prolonged coag times (PT, aPTT), low fibrinogen

Recognize *jugular venous tracing of atrial contraction*

first peak wave = a wave = atrial contraction = absent in patients with atrial fibrillation

During period of 24 hours, a 25-year-old man has an upper respiratory infection with features of common cold. What viral or host factors is most critical in the initial establishment of the infection?

*Presence of viral receptor molecules on epithelial cells* Rhinovirus = picornavirus = nonenveloped RNA virus = cause of common cold = acid labile = destroyed by stomach acid - *ICAM1 (CD54) receptor*

Investigator studying function of voltage-gated sodium channel develops mutant form of channel that inactivates more rapidly than normal. What is the most likely effect of this mutation on the electrical properties of the neuron?

*Decreases amplitude of action potential* - voltage gated sodium responsible for upstroke of AP - inactivation gates terminate upstroke of AP - earlier termination of AP upstroke = decreased amplitude of AP - threshold was still reached, so AP occurred = AP amplitude was just stunted

26 yo woman comes to office for follow-up. Patient & her husband want to have a child, & she inquires about the risk of certain genetic conditions, including CF. The patient is from a small city with a stable Caucasian population, where the carrier frequency for CF is 1/30 Caucasian individuals. Her husband is from a nearby community, where CF carrier frequency in individuals of Asian descent is 1/100. Both the patient, who is Caucasian, & her husband, who is of Asian descent, are healthy. What is the probability that a child born to a mother from the Caucasian community & a father from the Asian community will have the disease?

*1/12,000* AR disease - patient = Caucasian = 1/30 probability of carrying CFTR allele - husband = Asian = 1/100 probability of carrying same allele To develop CF, child must independently inherit mutant allele from each parent = 1/2 x 1/2 = 1/4 probability P(affected child) = 1/4 x P(carrier mother) x P(carrier father) = 1/4 x 1/30 x 1/100 = 1/12,000

Screening program instituted for detection of vaginal Chlamydia trachomatis infection among first-year women college students. At initial screening, evidence of C trachomatis infection found in 500 of 2500 students. One year later, screening shows vaginal C trachomatis in additional 200 students. What is the annual incidence of C trachomatis infection in this population of women students?

*10%* Incidence = number of new cases / population AT RISK 500 of 2500 tested positive for disease --> leave 2000 at risk for next year --> 200/2000 = 10%

In a historical study, 4753 nulliparous women with confirmed pregnancies were randomized to either folic acid supplementationof trace element supplementation. In both the folic acid and trace element groups, 88% of the women had pregnancies ending in live birth, late fetal death, stillbirth, or termination of pregnancy after prenatal diagnosis of a defect. the following pregnancy outcomes were found: Drug: Folic Acid ~ Trace Elements Neural tube defects: 0% ~ 0.29% All Congenital anomalies: 1.3% ~ 2.3% Based on these data, using the trace element group as a control group, which of the following best represents how many nulliparous women with confirmed pregnancies would have to be treated with folic acid to prevent one congenital abnormality?

*100* NNT = 1/ARR ARR = Event rate in control group - Event rate in treatment group ARR= 2.3% - 1.3% = 1% = 1/100 = 0.01 So, 1/0.01 = 100

In a survey of 100 households (average three residents per household), 45 individuals with asthma are detected. What is the best estimate of the prevalence of asthma?

*15%* - each household = average of 3 ppl - 100 households x 3 = 300 individuals - Prevalence = 45/300 = 15%

45 yo woman comes to doc for follow-up exam 8 wks after beginning tamoxifen therapy for estrogen- & progesterone-positive invasive ductal carcinoma of breast. Her 50 yo sister also has hormone-sensitive breast cancer treated with tamoxifen. Physical exam shows no abnormalities. Serum studies show decreased concentrations of endoxifen, the active metabolite of prodrug tamoxifen. Genetic analysis shows homozygous presence of cytochrome P450 2D6*4 alleles. What best represents the likelihood that this patient's sister has same alleles?

*25%* Enzyme deficiencies usually AR... - pt is homozygous for described allele (AA), so parents must have been heterozygote carriers (Aa) - chances of her sister having both alleles = 1/4 - assume parents are Aa & not AA bc in general population, there are more heterozygote carriers than ppl with disease

Study conducted to assess 32 patients in community of 1000 who have developed drug-resistant tuberculosis during 1-year period. These patients are removed from community for treatment. Assuming that the risk for infection and susceptibility to disease is constant, what best represents the number of individuals most likely to develop subsequent drug-resistant tuberculosis during the next year?

*31* 32 / 1000 = 3.2% 1000 - 32 = 968 0.03 x 968 = 31

FDA will approve new drug if KM28 plus standard care decreases rate of breast cancer recurrence by at least 40% compared to standard therapy alone. The recurrence rate on standard therapy is found to be 8%. In order to approve KM28, what is the maximal incidence of recurrent disease acceptable for women treated with KM28 plus standard therapy?

*4.8%* 40% of 8% = 3.2% Max acceptable recurrencec rate = 8% - 3.2% = 4.8%

24 yo man with history of IV drug use brought to ED by his roommate 30 minutes after he could not be aroused. Friend reports that patient injected himself with drug approximately 6 hours ago. Lab studies show serum drug concentration of 0.30 mg/L. Assuming drug exhibits first-order one-compartment kinetics, has a half-life of 2 hours, and a volume of distribution of 200 L in this patient, what is the most likely approximate quantity of the drug (in mg) injected?

*480* Total concentration = 0.30 mg/L x 200 L = 60 mg 6 hours ago drug was taken... Right now, there's 60 mg in body Half life = 2 hours Go backwards... 6 hours = 60 4 hours = 120 2 hours = 240 0 hours (time of injection) = 480 mg

An examination is scaled so that the scores are approximately normally distributed with a mean of 500 and a standard deviation of 100. What is the percentage of examinees with scores between 400 and 600?

*67%* Normal distribution: +/- 1 SD = 68% +/- 2 SD = 95% +/- 3 SD = 99.7%

Numbers of patients treated with Superstatin: MI = 10 No MI = 990 Number of patients treated with control meds MI = 25 No MI = 975 Compared to control med, how many patients need to be treated with Superstatin to prevent one additional MI?

*67* NNT = number of patients that need to be treated with me in order to prevent additional negative outcome = 1/absolute risk reduction (ARR) ARR = event rate in control group (25/1000 = 0.025) - event rate in treatment group (10/1000 = 0.01) = 0.015 1/0.015 = 66.6 = 67 patients need to be treated with Superstatin to prevent additional MI

35 yo woman given 500 mg of drug X IV. Several minutes later, the serum concentration of drug X is 12.5 mg/L. Two hours later, the serum concentration is 10 mg/L. Assuming that drug X has first-order elimination kinetics, what will be the serum concentration of drug X (in mg/L) in another 2 hours?

*8* 12.5 - 10 = 2.5 2.5 is 1/5 of 12.5 1/5 of 10 is 2 10 - 2 = 8

Assume that any single laboratory test in a three-test battery obtained from healthy volunteers has a 5% chance of falling outside of the "normal" range. Which of the following is the closest probability that a healthy person will have normal results for all three tests?

*85%* .95*.95*.95=.85

Where on pressure-volume loop of cardiac cycle would mitral stenosis occur?

*A* Mitral stenosis = opening snap followed by diastolic rumbling murmur heard best over apex of heart = between isovolumetric relaxation and diastolic filling

40 yo Caucasian male dies in motor vehicle accident. He has been a one pack-per-day cigarette smoker, & was moderately overweight. His fam history is significant for: a MI in his father at age 48, & a stroke in his mother at 58. Which of the vessels is most likely to show atherosclerotic involvement in this patient at autopsy?

*Abdominal aorta* Atherosclerotic plaques - develop predominately in large elastic arteries = aorta, carotid, iliac arteries - *abdominal aorta = most heavily involved* = around ostia of major arterial branches

If lateral (fibular) collateral ligament is torn by a fracture, what conditions may occur?

*Abnormal passive adduction of extended leg* Lateral (fibular) collateral ligament = prevents adduction at knee - torn = recognized by abnormal *adduction* of extended leg

36 yo woman noticed lumps her arm while getting dressed. She says she feels fine & has no other symptoms. Med history is significant for hypothyroidism. Fam history is negative. Body mass index is 24 kg/m^2. Breast exam shows nontender left axillary lymphadenopathy. Patient is sent for ultrasound-guided biopsy. Microscopy of tissue specimen shows clumps of cells that have positive immunohistochemical staining for cytokeratin. Cells identified by special immunohistochemical stain are shown to overexpress 185 kD glycoprotein that spans cell membrane & has tysosine kinase activity in intracellular domain. What is the most likely function of this protein?

*Accelerates cell proliferation* HER2 oncogene = codes for human epidermal growth factor receptor with tyrosine kinase activity in intracellular domain HER-2 positive breast cancers = higher risk of recurrence = worse prognosis - trastuzumab used

50 yo man comes to physician because of 2 month history of chronic abdominal pain. He also has had intermittent mild knee pain since playing college football 30 years ago; the pain has become more constant during past 5 weeks. Physical exam shows mild epigastric tenderness and decreased range of motion of both knees. Endoscopy shows an antral ulcer. What drug is most appropriate in this patient?

*Acetaminophen* - not associated with GI irritation or cardiovascular risk

80 yo woman being evaluated for suspected temporal arteritis (TA). Her ESR is 100 mm/h. Treatment of TA involves use of glucocorticoids, which could have serious adverse effects. Pretest probability for TA is 50% in this patient. In evaluation of TA, ESR has sensitivity of 99% & a specificity of 60%. Based on the results of the ESR testing in this patient, what is the most appropriate next step in management?

*Additional testing to confirm the diagnosis of TA* - sensitivity = way of ruling out diseases - elevated ESR & sensitivity of 99% = you cannot eliminate TA from differential - with a single blood test, you are never 99% sure of diagnosis - other things can cause elevated ESR,hence low specificity - for TA, gold standard = temporal artery biopsy - if your suspicion is high enough, start corticosteroids BEFORE biopsy to ensure no further progression of disease

56 yo man evaluated in clinic due to worsening lower extremity pain & weakness. Patient has had hematuria & intermittent burning on urination for past year. He has no history of pelvic trauma or surgery. Patient has smoked pack of cigarettes daily for past 35 years. His urine culture is negative for bacterial growth. Urine cytology & cytoscopy confirm diagnosis of transitional cell carcinoma. Abdominal CT shows advanced bladder tumor compressing nerve that passes through obturator canal. What actions would most likely be impaired in this patient?

*Adduction of thigh* Obturator nerve = from lumbar plexus = L2-L4 = supplies obturator externus --> divides into anterior & posterior branches that supply rest of thigh adductor muscles (adductor longus, brevis, magnus) - anterior division gives off terminal cutaneous branch = sensation over distal medial thigh

48 yo man brought to ED 2 hours after injuring his leg when he slipped and fell on icy sidewalk. Physical exam shows obvious lateral swing of leg when he walks. X-rays of left lower extremity show no fractures. An injury to the left obturator nerve as it passes through the obturator foramen is suspected, & physical therapy is initiated. This patient's gait abnormality is most likely to be corrected by strengthening the muscles that control what movements of the left proximal lower extremity?

*Adduction* Damage to obturator nerve = weakeness of adduction = lateral swinging of limb during walking because of unopposed abductors

Scientific investigators develop vaccine against Neisseria meningitidis that contains meningitidis that contains meningococcal pilus antigens. Vaccine admin in lab mice induces production of monoclonal Abs against pilus proteins which are found to impair normal pili function. The efficacy of these antibodies in preventing infection would most likely depend on direct interference with what processes?

*Adherence to nasopharynx epithelial cells* Meningococci = commonly isolated from oropharynx & nasopharynx of asymptomatic carriers - attach to & colonize pharynx via pilus-mediated adherence to mucosal epithelial cells

Four children & 2 adults currently being followed in nephrology clinic for post-streptococcal glomerulonephritis. Three patients initially presented with gross hematuria & edema requiring diuretic admin. The remaining 3 patients presented with microscopic hematuria & HT. C3 levels were decreased in all patients, & anti-streptolysin was elevated in 4 of the patients. None of these patients have pre-existing renal disease. What patient characteristics is most likely to indicated a poor long-term prognosis?

*Adult onset* Post-streptococcal glomerulonephritis (PSGN) - most common cause of acute pediatric GN - acute onset of malaise, periorbital edema, HT, microscopic or gross hematuria (cola- or tea-colored) children ages 5-12 = >95% recovery in children *Increased age = poor prognostic factor* - only 60% of adult cases resolve completely - the rest = chronic HT, recurrent proteinuria, chronic renal insufficiency, rapidly progressive GN

46 yo woman dies in hospital from respiratory failure after prolonged illness. She has multiple comorbidities, including advanced renal disease. Autopsy reveals multiple, small, nondestructive masses attached to edges of mitral valve leaflet. Microscopy reveals that masses are composed of platelet-rich thrombi, but cultures reveal no bacterial growth. What diseases is most likely associated with this patient's condition?

*Advanced malignancy* Nonbacterial thrombotic endocarditis - sterile platelet-rich thrombi attached to mitral valve leaflets = marantic endocarditis = most commonly associated with *advanced malignancy*, as well as chronic inflammatory disorders such as antiphospholipid syndrome, SLE (Libman-Sacks endocarditis), & DIC in patients with sepsis - often seen in mucinous adenocarcinomas, which may related to procoagulant effects of circulating mucin

Decision is made to insert a central venous catheter. In addition to sterile draping during the procedure, what actions would be most likely to prevent intravascular catheter-related infections?

*Alcohol-based hand scrub prior to beginning the procedure* CVCs = used for hemodynamic monitoring & admin of fluids & meds in critically ill patients - gram-positive cocci (coag-negative staph & staph aureus = majority of infections) CDC recommendations for reducing CVC infections - hand hygiene = alcohol sterilizer or soap & water prior to donning sterile gloves - max barrier precautions during insertion (surgical mask, sterile gloves, long-sleeved surgical gown, large sterile sheet drape) - use of subclavian or internal jugular insertion sites (femoral vein has higher risk of infection) - prompt removal of catheter when no longer needed

20 yo college student receives severe blow on inferolateral side of left knee joint while playing football. Radiograph exam reveals a fracture of head & neck of fibula. What arteries could be damaged by this fracture?

*Anterior tibial* - arises from popliteal artery --> enters anterior compartment by passing through gap between fibular & tibia at upper end of interosseous membrane

Basketball player hit in thigh by opponent's knee. What arteries is likely to compress and cause ischemia because of bruise & damage to extensor muscles of leg?

*Anterior tibial* - muscular spasm or hypertrophy of extensor muscle of leg may compress anterior tibial artery = ischemia

12 yo boy brought to ED because of difficulty breathing, wheezing, & nonproductive cough. He has visited ED seven times over past year because of similar symptoms. Physical exam reveals decreased bilateral breath sounds, prolonged expirations, & end-expiratory wheezes. Chest x-ray shows hyperinflated lungs with no infiltrates. He is treated with inhaled beta-agonists & corticosteroids. He significantly improves & is discharged on tapered-dose oral corticosteroids. He comes to ED 2 weeks later in severe respiratory distress with similar symptoms & requires endotracheal intubation. What therapies will most likely decrease likelihood of such events happening in the future?

*Anti-IgE antibodies* Anti-IgE Abs given as subcutaneous injection (omalizumab) have been shown to be effective in patients with moderate-to-severe allergic asthma Omalizumab = recombinant humanized IgG1 monoclonal antibody that binds IgE --> inhibits action of IgE with receptor on mast cells, basophils, & other cell types & decrease allergic response

27 yo woman, gravida 3 para 0 aborta 3, comes to office for evaluation of fertility difficulties. Patient was started on combined oral contraceptive pills at age 22. She had no periods while using oral contraceptives & was advised that this was normal & of no concern. The patient stopped her contraception a year ago in an attempt to conceive with her husband but still has not menstruated. Her past medical history includes 3 elective first-trimester pregnancy terminations in her late teens. TSH, FSH, LH, prolactin, & quantitative beta-hCG are normal. As part of the evaluation for amenorrhea, 10 days of oral medroxyprogesterone is administered. A few days after completing her progesterone course, the patient has moderately heavy bleeding with some cramping. What endometrial processes cause the bleeding?

*Apoptosis* Progesterone - secreted in luteal phase of menstrual cycle When endometrium is no longer exposed to progesterone (progesterone withdrawal test)... - prostaglandin production increases = vasoconstriction of spiral arteries = increases secretion of metalloproteases by endometrial stromal cells = degradation of extracellular matrix & apoptosis of endometrial epithelium - net effect = degeneration of functionalis layer = sloughs away = menstrual flow

64 yo man brought to ED after motor vehicle accident where his chest hit the steering wheel. His temp is 36.7 C (98 F), BP is 132/78 mmHg, pulse is 76/min, & respirations are 14/min. Patient has no known chronic medical problems & takes no med. Physical exam reveals mild tenderness over lower right chest. Imaging of neck & chest shows no fractures or dislocations. However, chest x-ray reveals pleural thickening & calcifications along posterolateral midlung regions & diaphragm. There is also a small right-sided pleural effusion. This patient most likely has a history of exposure to what agents?

*Asbestos* - calcified lesions = pleural plques = hallmark = especially between 6-9th ribs = 20-30 year latency between asbestos exposure & onset of symptoms

56-year-old woman with major depression comes to office for follow-up. She has been on paroxetine 40 mg daily for past 2 years. She is doing fairly well but still experiences some periods of depression. When the patient is asked whether she is having any difficulty with meds, she explains that she doubles her does when having a "bad day" and occasionally skips doses on days when she feels better. What would be the most appropriate action by her physician?

*Educate the patient about the risks of irregular dosing*

66 yo man comes to ED due to dizziness, dysarthria, & bilateral limb ataxia. His symptoms have been steadily worsening over last 2 weeks. He has no other medical problems & takes no meds. He has 50-pack-year smoking history & does not use alcohol or illicit drugs. Chest x-ray shows mass in his right lung. He is admitted to hospital for evaluation, but his neurologic symptoms continue to progress. Autopsy shows extensive Purkinje cell degeneration. What best describes etiology of this patient's neurologic condition?

*Autoimmune* Paraneoplastic cerebellar degeneration - lung mass, cerebellar symptoms, autopsy - progressively worsening dizziness, limb, & truncal ataxia, dysarthria, visual disturbances (diplopia, oscillopsia) Via immune response against tumor cells that cross-reacts with Purkinje neuron antigens = acute-onset rapid degeneration of cerebellum - Anti-Yo, anti-P/Q, anti-Hu = most common Abs detected in serum

Anterior horn cells of spinal cord of experimental animal demonstrate cell body rounding, peripheral displacement of nuclei & dispersion of Nissl substance to periphery of cells. The findings described most likely indicate:

*Axonal reaction* = changes seen in neuronal body after axon is severed - cell body grows = cellular edema - swollen & rounded - nucleus displaced to periphery - Nissl substance becomes fine, granular & dispersed throughout cytoplasm = central chromatolysis - becomes visible in 24-48 hours after injury - reflect increased synthesis of protein by cells in order to regenerate severed axon = reversible

28 yo woman brought to physician because of 3-week history of double vision. One year ago, she had episode of blurry vision in her left eye that gradually improved during next 2 months without treatment. Neuro exam shows that right eye does not adduct past midline on horizontal gaze when looking to left. When convergence is tested, right eye is able to adduct past midline. Rightward horizontal gaze is normal. This patient most likely has lesion involving what labeled structures in photomicrograph of brain stem shown?

*C* MLF = anterior to aqueduct & in middle as name implies INO (Internuclear Ophthalmoplegia) affects ipsilateral side = right side

67 yo woman comes to clinic due to decreased vision in her right eye that she noticed a week ago. Patient says that her sight in the right eye is "narrower" than in the left. Her past med history is significant for HT, type 2 DM, & hyperlipidemia. She also suffers from intermittent lower limb claudication & has had 2 prior episodes of transient vision in her right eye. Visual field testing reveals right nasal hemianopia. MRI/magnetic resonance angiography of head & neck reveal a right internal carotic artery aneurysm. What portions of the visual pathway is most likely disrupted in this patient?

*B* - light from nasal visual field strikes temporal side of each retina, & optic nerve fibers from temporal part of retinal travel laterally through optic chiasm to pass into ipsilateral optic tract *lesions of lateral aspect of optic chiasm = ipsilateral nasal hemianopia* by damaging uncrossed, temporal retinal fibers - via aneurysm of internal carotid artery (cavernous or opthalmic segments)

42 yo woman comes to physician because of 3-week history of numbness of fingers on left hand. Neuro exam shows loss of touch graphesthesia & loss of two-point discrimination in left hand. This patient most likely has a lesion in what location of hemisphere?

*B* Lesion in postcentral gyri / primary somatosensory area - central sulcus dividing between B & C = divides precentral gyri / primary motor cortex from postcentral gyri / somatosensory cortex - problem on right hemisphere since he has problem with dorsal column (touch and two point discrmination) = gracilis cuneatus = upper extremities

To determine whether ACEIs are superior to CCBs in preventing renal disease progression in patients with newly diagnosed type 1 DM, what is the major advantage of a randomized controlled trial versus a prospective cohort study?

*Better control for confounding variables* Confounding bias - when factor related to both exposure and outcome, but no on causal pathway Strategy to reduce bias - multiple/repeat studies - crossover studies (subjects act as their own controls) - matching (patients with similar characteristics in both treatment and control grups) - washout period - restriction - *randomization*

Case-control study is conducted to explore possible association between exposure to herbicide and diagnosis of non-Hodgkin lymphoma. Controls are matched to cases by age, gender, and race. Exposure status is determined by interviewing subjects. On matched-pair analysis, the odds ratio is 3.2 (95% CI: 1.4 - 5.4). What is the most likely to affect the validity of this study?

*Biased measurement of exposure* - person may be more likely to recall or overestimate exposure to potential risk factor if they become ill (become a case) & a person without disease often tend to forget an exposure to risk factor This case... - those subjects who got lymphoma are more likely to recall exposure to herbicide (if in fact there is an association) than those subjects who are lymphoma-free (i.e. even if healthy subjects whose were exposed to herbicide, some may not be able to recall the exposure & this will result in increase in measured odds ratio for suspected herbicide - affecting validity of study results)

Recognize where, on an aortic regurgitation graph, you would hear the murmur best

*C* - peak intensity *after aortic valve closure* AR - high peaking left ventricular & aortic pressures during systole - loss of dicrotic notch - steep diastolic decline in aortic pressure = wide pulse pressure = heard best along left sternal border at 3rd & 4th ICS while patient is sitting up & leaning forward with breath held at end-expiration

Leading nephrology research institute is investigating kidney's ability to clear various substances from plasma. Healthy volunteer is given slow IV infusion of para-aminohippuric acid. Concentration of this substance is most likely to be lowest in what nephron segments?

*Bowman's space* PAH - majority secreted by proximal tubule via carrier-mediated active transport - not reabsorbed by any portion of nephron

Patient was employed as construction worker for over 30 years and recently received letter from employer stating that he had significant exposure to asbestos early in his career. The patient is now concerned about his risk of developing cancer. What types of malignancy is this patient most likely to develop?

*Bronchogenic carcinoma* - most common malignancy associated with asebstos exposure - smoking and asbestos exposure = synergistic effect on dev't Asbestos = naturally occurring mineral = insulating properties used in shipbuilding, construction, textile industries = pleural plaques = diffuse pulmonary fibrosis = malignant mesothelioma = rare

54 yo male brought to ER with one-week history of headaches & progressive confusion. He was hospitalized six months ago with viral esophagitis & two months ago with pneumocystic pneumonia. Lumbar puncture performed, & shows a moderate increase in CSF protein concentration & CSF pleocytosis. Latex agglutination test is positive for soluble polysacchairde antigen. Light microscopy of this patient's CSF is most likely to reveal:

*Budding yeast* HIV infection = viral esophagitis + pneumocystis pneumonia Meningitis = headache + confusion + inflammatory CSF CNS infection in HIV + patient = Cryptococcus neoformans - latex agglutination test detects polysaccharide capsule antigen - India ink stain = round or oval budding yeast

65 yo male with long history of smoking comes to office due to nonproductive cough over last several months. He recently developed left shoulder pain, persistent hiccups, & dyspnea. His temp is 36.7 C (98 F), BP is 140/85 mmHg, & pulse is 76/min. Physical exam reveals decreased breath sounds on left side. Chest x-ray shows large left lung mass. Compression of a nerve arising from what locations is most likely causing this patient's recent symptoms?

*C3-C5* Lung cancer = intrathoracic expansion --> phrenic nerve irritation & palsy Phrenic nerve - arises from C3-C5 cervical segments --> innervates ipsilateral diaphragm - irritation = dyspnea, hiccups, referred pain to should - palsy = resp distress & diminished breath sounds on affected side with elevation of affected hemidiaphragm on chest x-ray

Mediates biceps & brachioradialis reflexes

*C5-C6* - biceps reflex performed by quickly tapping hammer against biceps brachii tendon as it passes through cubital fossa - also controls brachioradialis reflex

What cell types is most likely to predominate in bronchoalveolar lavage fluid of patient with sarcoidosis?

*CD4+ T lymphocytes* - accumulation of CD4+ T cells in areas of active disease = predominance of CD4+ T cells & high CD4+/CD8+ ratio (>2:1) in bronchoalveolar lavage fluid

23 yo male runs five miles. What do you expect to increase at the peak of his exertion?

*CO2 content in MIXED VENOUS blood* Aerobic exercise = increased oxidative metabolism of glucose & FAs in skeletal muscle - increased rate of both oxygen consumption & CO2 production - venous blood CO2 content is increased via increased CO2 production - venous blood pH decreased

Gram positive bacteria inoculated under skin of experimental animals & then infection is treated with antibiotics. Bacteria isolated from injection site several days later assume a spherical configuration when placed in isotonic solution & disintegrate rapidly when placed in hypotonic solution. What antibiotic was most likely used in this experiment?

*Cefuroxime* / Cephalosporins, Penicillins, Vancomycin - able to disrupt peptidoglycan cell wall of gram positive & gram negative organisms - ability to survive osmotic stress is lost after treatment with antibiotics - gram positives have cytoplasmic membrane composed of phospholipid bilayer as well as peptidoglycan cell wall outside of cell membrane = shape of bacterium as well as resistance to osmotic stress - organisms in stem were destroyed by placement in hypotonic solution = damaged to peptidoglycan cell wall by antibiotic used

18 yo man brought to ED with 1-day history of fever, headaches, nausea, vomiting, & myalgias that began suddenly last night. This morning, his roommate found him confused & difficult to arouse. The patient is an exchange student who came to the US 3 months ago to attend a local university. His temp is 39.4 (103 F), BP is 100/60 mmHg, pulse is 112/min, & respirations are 18/min. Physical exam shows nuchal rigidity & purpuric rash on his lower extremities. CSF analysis is notable for elevated leukocyte count, high protein, & low glucose. Review of his records shows that he did not receive vaccine that could have prevented this infection. What does this vaccine contain?

*Capsular polysaccharide* Meningococcal meningitis: Neisseria meningitidis - dorms = transfer Meningococcal vaccines - polysaccharide quadrivalent vaccine & conjugate vaccines - quad = against subtypes A, C, Y, W-135 - conjugate = better, long-lasting protection = conjugated to diphtheria toxoid protein - vaccines against subtype B have recently been introduced - recommended for adolescents ages 11-18 & close living condition ppl

3 week old boy brought to ED with fever, irritability, & poor feeding. Exam of CSF shows leukocyte count of 600 cells/uL (80% neutrophils), protein of 160 mg/dL, & glucose of 20 mg/dL> Blood cultures grow gram-negative rods that form pink colonies on MacConkey agar. What is the most important bacterial virulence factor for dev't of this patient's condition?

*Capsule* Meningitis secondary to E coli = motile, gram-negative, facultative anaerobic rod = ferments both lactose & glucose K1 capsular antigen = 20-40% of intestinal E coli isolates = major virulence factor among E coli strains that cause neonatal meningitis

In a study to assess whether neck irradiation is a risk factor for thyroid cancer, the researchers identify a group of patients with thyroid cancer and a similar group of patients without thyroid cancer. History of prior neck irradiation is obtained from each group based on strict criteria for exposure. This type of study is best described as what?

*Case-control* - compares group of people with disease to group without disease - looks to see if odds of prior exposure or risk factors differs by disease state - asks, "what happened?" = odds ratio

75-year-old man brought to ED due to problems with vision & right-sided hemisensory loss that started an hour ago. While in the ED, his symptoms gradually worsen & he develops a headache. Head CT reveals multiple, small lobar hemorrhages of varying ages in the occipital & parietal areas with medium-size acute bleed in the left parietooccipital lobe. Two years ago, the patient developed sudden right arm weakness; neuroimaging at that time demonstrated a small left frontal hemorrhage. He has no head trauma & does not use anticoagulants. This patient most likely suffers from what?

*Cerebral amyloid angiopathy* - elderly patient with recurrent lobar hemorrhage - beta-amyloid deposition in walls of small- to medium-sized cerebral arteries = vessel wall weakening & predisposition to rupture - recurrent - most often involves occipital parietal lobes Occipital lobe hemorrhage - homonymous hemianopsia Parietal hemorrhage - contralateral hemisensory loss Amyloid angiopathy = most common cause of spontaneous lobar hemoarrhage (adults >60)

Recognize *granuloma* Case: "10 year old girl has slightly painful 2-mm subcutaneous nodule on her chin. Ten weeks ago, she required sutures after she lacerated her chin playing basketball. A photomicrograph of tissue obtained on biopsy is shown. What best describes the pathologic process?

- try to contain infection by creating a big "wall" around it

GI symptoms of a patient who has Traveler's Diarrhea after going to Honduras related to toxin similar to what?

*Cholera-like toxin* ETEC = diarrhea in infants & travelers in developing countries or regions with poor sanitation - colonization in SI via adhesion mediated by pilli - elaboration of heat labile (LT) &/or heat stable (ST) enterotoxins (plasmid encoded) LT enterotoxin = similar to cholera toxin = increases cAMP by activating stimulatory Gs membrane G protein

62 yo woman has abdominal aneurysm repaired. Forty-eight hours after surgery, her distal leg is dusky and cool and there are dark purple-to-black necrotic lesions on several toes are shown. A biopsy of one of the lesions would most likely show occluded small arteries with needle-shaped clefts. What is the most likely cause of the lesions? (affected foot shown)

*Cholesterol emboli* = atheroembolic renal disease = caused by showers of cholesterol-containing microemboli - arise in atheromatous plaques in major arteries - in patients with widespread atheromatous disease - usually after interventions such as surgery or arteriography Accompanying signs = microvascular occlusion in lower limbs (ischemic toes, livedo reticularis)

6 yo boy playing in dusty field in windy weather inhales many small particles that become lodged in his terminal bronchioles. What respiratory components is most important in clearing these particles?

*Ciliated cells* Mucociliary clearance - ciliated mucosal epithelium lines pulmonary airways from trachea to proximal portions of respiratory bronchioles Terminal bronchioles = covered by ciliated cuboidal epithelium & club cells --> mucociliary clearance in this region

Previously healthy 27 yo man comes to physician because he has had cough productive of blood-tinged sputum for 4 days. His BP is 160/100 mmHg. His serum creatinine concentration is 4.8 mg/dL. Urinalysis shows erythrocyte casts. Immunofluorescence microscopy of a renal biopsy specimen shows linear deposits of IgG in glomeruli. What histologic abnormalities in the glomerulus is most likely?

*Crescent formation* Rapidly progressive (crescentic) glomerulonephritis: Goodpasture - type II HS - lungs + kidney - young males

Meta-analysis of several trials on effect of cocoa intake on systolic BP (SBP) revealed results: Study: Mean SBP in cocoa group - mean SBP in control group [95% confidence interval] A: -5.2 [-7.3, -3.4] B: 1.6 [-5.3, 10.4] C: -4.2 [-8.1, -2.7] D: -2.9 [-4.1, -1.4] E: -2.8 [-5.2, -1.1] F: 0.8 [0.1, 1.2] G: 1.0 [-1.2, 3.3] Total: -2.2 [-2.7, -1.3] All the trials evaluated the difference in SBP at 2 weeks. Based on the data, what is the most appropriate conclusion?

*Cocoa intake was associated with statistically significant decrease in systolic BP* Meta-analysis = results of several trials to increase statistical power & provide overall estimate of effect of exposure on outcome - pooled effect estimate This example... - overall change in mean SBP of -2.2 mmHg = decrease in SBP compared to control group - corresponding 95% CI = -2.7 to -1.3 mmHg - range does not include null value (0 mmHg in this case) = statistically significant = cocoa intake was associated with statistically significant decrease in SBP - null value corresponds to 0 mmHg = no different between cocoa intake & control groups - 95% CI of [-2.7, -1.3] = entirely negative = does not cross - = statistically significant

63 yo female concerned about wrinkles around her eyes that make her "look old." A decrease in what is most likely responsible for this patient's complaint?

*Collagen fibril production* UVA = penetrate deeper into skin = photoaging = reactive oxygen species --> decreased collagen fibril production, upregulation of matrix metalloproteinases (including collagenases) that subsequently degrade type I & III collagen & elastin Photoaging - may be visible by age 30-35 - gradual thinning of epidermis - rete ridges at dermoepidermal junction become flattened - increased crosslinking of collagen --> deposition of collagen breakdown products

Gram-negative bacteria isolated from patient's blood produces enzyme that splits IgA molecule at hinge region. What is likely to be the most important role of this bacterial enzyme in this course of infection?

*It facilitates mucosal adherence of bacteria* N gonorrhoeae, N meningitidis, Strep pneumoniae, H influenzae - produce IgA proteases --> cleave IgA at hinge region = Fab & compromised Fc fragments = decreases its effectiveness --> facilitates bacterial adherence to mucosa

40 yo woman undergoes chorionic villus sampling at 11 weeks' gestation because of her age-related increase for having a child with aneuploidy. Chromosome analysis shows 46,XY in 14 cells studied and 47,XY+15 in an additional 25 cells studied. Subsequent chromosome studies of amniotic fluid show 46,XY in 50 cells. What best explains this difference?

*Confined placental mosaicism* = discrepancy between chromosome makeup of cells in placenta and cells in body = diagnosed when some trisomic cells are detected on chorionic villus sampling and only normal cells are found on subsequent prenatal test, such as amniocentesis or fetal blood sampling - when trisomic cells are found only in placenta = 1-2% of ongoing pregnancies that are studied by chorionic villus sampling at 10-12% weeks of pregnancy

38 yo man with 3 yr ho type 2 diabetes mellitus comes to physician for follow-up exam. In addition to taking oral antihyperglycemic agent, he has tried controlling his condition with diet modifications and exercise. He is 6 ft 2 in tall & weighs 250 lb; BMI is 32 kg/m^2. Physical exam shows no other abnormalities. His hemoglobin A1c is 10%. Physician recommends initiation of insulin injections to obtain better control over patient's blood glucose concentration. Patient responds, "I know insulin would help control my blood sugar. But a lot of ppl in my fam have diabetes, & insulin made them really sick at times." This patient is most likely at what stages of changes regarding insulin admin?

*Contemplation* - acknowledging that there is a problem, but not yet ready or willing to make change

Multinational research institute conducting experiments on human circulatory physiology enrolls healthy 30-year-old male volunteer to assess oxygen consumption rate of various organs. During study, blood oxygen content of aorta and several other vessels is measured at rest. The greatest difference in these measurements will most likely be between aorta and what other blood vessels?

*Coronary sinus* - arterial blood supply to cardiac muscle/mycocardium via right & left coronary arteries via aortic root - most coronary venous blood drains into right atrium via coronary sinus Heart muscle - perfused during diastole - oxygen extraction is very high = cardiac venous blood is the most deoxygenated - oxygen demand & coronary blood flow are tightly coupled

42 yo woman comes to ED for evaluation of chest pain. She was moving furniture in her summer house 2 days ago when she experienced sharp pain in the left side of the sternum that quickly subsided. Since then, the patient has had episodic pain with deep inspiration or trunk movement. She has no fever or cough. The patient has history of HT. Her father died of MI at age 67. She does not use tobacco or illicit drugs. BP is 146/85 mmHg in her right arm & 142/80 mmHg in her left arm, pulse is 86/min, & respirations are 12/min. She has localized tenderness to palpation at left sternal border. Lungs are clear to auscultation, & cardiac exam reveals normal heart sounds without gallops or murmurs. The abdomen is soft & nontender. There is no peripheral edema. What is the most likely cause of this patient's symptoms?

*Costochondritis* / Costosternal syndrome / Anterior chest wall syndrome - regional chest wall - after repetitive activity - involves upper costal cartilage at costochondral or costosternal junctions - reproduced with palpation & worsened with movement or changes in position (horizontal arm flexion)

32 yo carpenter fell from roof. Lateral longitudinal arch of his foot was flattened from fracture & displacement of keystone for arch. What bones is damaged?

*Cuboid bone* = keystone for lateral long. arch

What pathophysiologic processes is involved in Niemann-Pick disease?

*Decreased lysosomal hydrolase* Niemann-Pick = lysosome malfunction disease - all sphingolipidoses = problem with lysosomal enzymes

When actively dividing E coli is exposed to drug, enzyme-mediated nucleotide removal in 5' to 3' direction is impaired, leading to inhibition of bacterial growth. What enzymes is the most likely target of this drug?

*DNA polymerase I* = only prokaryotic polymerase with 5' to 3' exonuclease activity --> removes RNA primer created by RNA primase & repairs damaged DNA sequences Prokaryotes, such as E coli = 3 major DNA polymerases = I, II, III

Previously healthy 2 yo boy brought to clinic with fever & mouth pain that began yesterday. He has consumed an adequate amount of fluids but refuses to eat due to pain. Patient has no medical problems and takes no meds. Physical exam reveals swollen gums and vesicular, inflamed lesions on his hard palate and lips. He has enlarged and tender cervical lymph nodes. What is most likely responsible for this patient's condition?

*DNA virus, double-stranded, enveloped* HSV-1 = gingivostomatitis = vesicles of lips & hard palate, fever, lymphadenopathy = lip lesions less severe Herpesviruses = enveloped = dsDNA = Tzanck smear

32 yo woman has had fecal incontinence since giving birth to her first child 1 year ago. What is the most likely cause of fecal incontinence in this patient?

*Damage to anal sphincter* Third-degree tears = involve skin, tissue under skin, and muscles of anal sphincter - most important step in preventing anal sphincter laceration at vaginal delivery = restricting use of midline episiotomy

60 yo woman comes to ED with shortness of breath & productive cough. She has 30-pack-year smoking history. Patient's oxygen saturation is 88% on room air. On physical exam, she appears uncomfortable & uses her accessory respiratory muscles. Expiratory wheezes are heard throughout lungs. Patient is started on high-flow oxygen supplementation. Shortly afterward, she becomes increasingly lethargic & confused. This patient's clinical decline is most likely attributable to increase in what?

*Dead space ventilation* COPD = long-standing smoking history, dyspnea, productive cough, hypoxia, expiratory wheezing, accessory muscle span - supplemental O2 may be warranted in patients with COPD who have hypoxia, BUT admin of excessively high O2 concentrations (hyperoxia) can lead to increased CO2 retention (oxygen-induced hypercapnia) = confusion & depressed level of consciousness (lethargy) Oxygen-induced hypercapnia = hyperoxia reverses pulmonary vasoconstriction --> increased physiologic dead space, as poorly ventilated alveoli are perfused (ventilation-perfusion mismatch) - increased PaO2 decreases Hemoglobin's affinity for CO2 = dissociation of bound CO2 from hemoglobin = increased pCO2 levels (Hadane effect) - high-flow oxygen reduces chemoreceptor stimulation = decreased respiratory rate & minute ventilation

Naive mouse thymocyte precursors obtained from normal active bone marrow genetically altered to constitutively express the gene, bcl-2, and combined with normal marrow cells for injection into mice whose active marrow has been destroyed by radiation. Control irradiated mice are injected with normal marrow alone. After recovery from the procedure, what differences is most likely to be observed in animals receiving the genetically altered cells as compared with control animals?

*Decreased cell death in thymic cortex* bcl2 = anti-apoptotic protein - always expressed = reduces cell death in thymic cortex in mice receiving genetically modified cells

67-year-old man come to office due to generalized weakness, easy fatigability, anorexia, & intermittent nausea for past several months. He also says that he is "itching and scratching a lot." Physical exam shows bilateral lower extremity pitting edema & skin excoriations. Lab results show serum creatinine level of 3.4 mg/dL & blood urea nitrogen level of 48 mg/dL. A renal biopsy is performed. Light microscopy of tissue sample shows widespread narrowing of renal arterioles with deposition of homogenous, glassy material in subendothelial space that stains pink with PAS-stain. This patient most likely has what condition?

*Diabetes mellitus* - hyaline arteriolosclerosis = homogenous deposition of eosinophilic hyaline material in intima & media of small arteries & arterioles Chronic kidney disease - accumulation of uremia toxins --> fatigue, weakness, itching

MRI of shoulder shows partial rotator cuff tear, & patient is scheduled for surgical repair. Immediately before surgery, he receives anesthesia with injection between right anterior & middle scalene muscles for blockade of brachial plexus. What muscles is most likely to be paralyzed due to anesthesia?

*Diaphragm* Interscalene nerve block = regional anesthetic for procedures involving upper arm & shoulder - anesthetic administered in scalene triangle - affects brachial plexus roots & trunks - *causes transient ipsilateral diaphragmatic paralysis in nearly all patients by anesthetizing roots of phrenic nerve (C3-C5) as they pass through interscalene sheath* - should be avoided in patients with chronic lung disease or with contralateral phrenic nerve dysfunction

Premenopausal 49 yo woman asks her physician about her risk for osteoporosis. Her mother had osteoporosis and disabling bone fractures after menopause. The patient works as a gardener for a landscape service & plays tennis 3 times a week. She does not smoke, drinks 1 glass of wine a week, & takes no medications. Her weight is 55 kg (121 lb). What additional info is needed to evaluate her risk for osteoporosis?

*Dietary history* Prophylaxis: regular weight-bearing exercise & *adequate Ca2+ & vitamin D intake throughout adulthood*

13 yo Caucasian female presents to your office with urine discoloration. She had been treated for facial impetigo three weeks ago. Urinalysis shows hematuria, mild proteinuria, & ocassional red blood cells. Renal biopsy is most likely to demonrate:

*Discrete subepithelial humps on electron microscopy* older child or young adult + edema + hematuria + proteinuria a few weeks after skin or pharyngeal infection = *poststreptococcal glomerulonephritis (PSGN)* - inflammatory condition involves all glomeruli in both kidneys - kidneys are enlarged & swollen - multiple surface punctuate hemorrhages LM: all glomeruli are enlarged and hypercellular via leukocyte infiltration & proliferation of endothelial & mesangial cells EM: electron-dense deposits (humps) on epithelial side of BM Immunofluorescence = granular deposits of IgG & C3 that have "lumpy-bumpy" appearance

4 yo boy is brought to ED for difficulty breathing & a productive cough. He has past medical history of recurrent episodes of sinusitis & otitis media. Respiratory infections typically have protracted course but respond to high-dose antibiotic therapy. Pulmonary auscultation shows crackles & wheezing. Cardiovascular exam shows cardiac point of maximal impulse that is palpated at right 5th intercostal space. What is most likely to be dysfunctional in this patient

*Dynein arms* Kartagener syndrome = recurrent respiratory infections & dextrocardia on physical exam = AR = via failure of dynein arms to develop normally = recurrent respiratory infections (chronic sinusitis, bronchiectasis) via impaired mucociliary clearance = can cause situs inversus = infertility in men & women

16 yo boy brought to ED 30 minutes after he dove into 3-foot-deep swimming pool at night. On exam, he is unable to move right upper & lower extremities. Most likely cause of movement deficits in this patient is damage to what labeled regions in the photograph of a cross section of the spinal cord shown?

*E* - lesion is at spinal cord level = right CST affected (ipsilateral)

2-week-old full-term female newborn develops pale stools and jaundice. The jaundice progresses; nuclear scans show no excretion of bile. Serum assay rules out alpha1-antitrypsin deficiency. Exam of tissue obtained on biopsy of liver shows inflammation and proliferation of small bile ducts and increased portal fibrosis. If not appropriately treated, this newborn is most likely to develop what?

*End-stage cirrhosis* Biliary atresia - bile duct - pathology = extrahepatic biliary tree - either failure to form lumen or early destruction - etiology = congenital or destruction due to infection - symptoms = biliary obstruction within first 2 months of life - complications = jaundice progresses to cirrhosis if untreated (biliary tree blocked = cholestasis in liver = cirrhosis) Usual history = full-term infant who appears normal at birth but develops jaundice after afe of 2-3 weeks - infant has yellow eyes & skin, light-colored stools, & dark urine caused by build up of bilirubin in blood - abdomen = swollen with firm, enlarged liver - weight loss & irritability develop as well as level of jaundice increased

62-year-old female presents to your office with several-month history of disturbing tingling & numbness in her feet. She has also noticed small ulcer on her right foot that doesn't seem to be healing. Her past medical history is significant for long-term diabetes, HT< & gout. Physical exam reveals decreased pain sensation over both feet & bilateral absence of ankle reflexes. This patient's neuro symptoms are most likely associated with what?

*Endoneural arteriole hyalinization* Peripheral neuropathy via diabetes mellitus - non-enzymatic glycosylation of protein --> increased thickness, hyalinization, narrowing of walls of arteries = diabetic microangiopathy of endoneural arterioles - ischemic nerve damage follows - intracellular hyperglycemia in peripheral nerves - accumulation of glucose --> sorbitol & fructose by aldose reductase - osmotic damage to axons & Schwann cells

18 yo man comes to urgent care clinic due to painful erythema affecting his extremities, trunk, & face. He is vacationing in Florida & spent 5 hours at Gulf coast beach earlier in day. Patient did not apply any sunscreen as it was cloudy. Physician explains that cloud cover does not afford high degree of protection against sun, especially with prolonged exposure in highly reflective env'ts like the beach. He is advised to wear protective clothing & apply sunscreen to prevent recurrence. What is most likely to happen within patient's skin cells as a result of his exposure?

*Endonuclease nicking of damaged DNA strand* UV rays - damage DNA via formation of abnormal covalent bonds between adjacent thymine or cytosine residues (pyrimidine dimers) --> interferes with base recognition during transcription & replication Pyrimidine dimers - removed by nucleotide excision repair - *endonuclease nicks damaged strandon both side of pyrimidine dimer & defective region is excised* --> DNA polymerase synthesizes new DNA In place of damaged DNA --> DNA ligase seals final remaining nick*

32 yo man who is an international health worker given primaquine against malaria. He becomes jaundiced. Lab findings are consistent with hemolytic anemia. The mechanism most likely to be responsible for this blood disorder is hemolysis due to ...

*Enyzme deficiency in erythrocytes* Hemolysis in G6PD deficiency - via isoniazid, sulfonamides, dapsone, primaquine, aspirin, ibuprofen, nitrofurantoin

What muscle can both dorsiflex & invert the foot?

*Extensor hallucis longus*

30 yo man with history of IV drug abuse & known HIV infection comes to ED because of increasing abdominal distention and anorexia. CT scan of abdomen shows ascites and large mass surrounding small intestine. Biopsy of mass reveals uniform, round, medium-sized tumor cells with basophilic cytoplasm and proliferation fraction (Ki-67 fraction) of > 99%. What infectious agents is most likely associated with development of his current condition?

*Epstein-Barr virus* (EBV) = t(8;14) = overexpression of c-MYC Burkitt lymphoma = diffuse medium-sized lymphocytes = high proliferation index represented by high Ki-67 fraction (approaching 100%) = starry sky appearance via benign macrophages

Erythema infectiosum / fifth disease / parvovirus B19 is highly tropic for what cells?

*Erythrocytes*

13 yo girl undergoing hematologic evaluation. She is found to have hemoglobin mutation that changes the partial pressure of oxygen at which hemoglobin is 50% saturated to 20 mmHg. In comparison, normal hemoglobin becomes 50% saturated with oxygen at 26 mmHg. What sequelae is this patient most likely to develop as a result of her mutation?

*Erythrocytosis* - P50 = 26 mmHg in normal individuals - P50 shift from 26 to 20 mmHg = affinity of hemoglobin for oxygen increased = left shift of oxygen dissociation curve Mutations that cause production of hemoglobin with high oxygen affinity = hemoglobins Chesapeake & Kempsey = reduced ability of hemoglobin to release oxygen within peripheral tissues Low oxygen levels --> stimulate kidneys to increase erythropoietin synthesis = compensatory erythrocytosis --> helps maintain normal oxygen delivery

What parameter is most likely to be elevated in patient with aplastic anemia? "24 yo man comes to clinic due to progressive weakness & fatigue over last 2 weeks. He has significant bruising on his trunk that developed spontaneously without any associated trauma. Patient has no known medical problems & takes no meds. Conjunctival pallor & truncal ecchymoses. Lab studies reveal hemoglobin of 6.8 g/dL. Aspirate is grossly pale & histologically appears dilute due to high lipid content."

*Erythropoietin* Aplastic anemia - via stem cell failure - affects all 3 cell lines = pancytopenia - increased erythropoietin by kidney (in response to anemia-induced hypoxia) = triad of: low hemoglobin, thrombocytopenia, absent hematopoietic cells

49 yo woman, gravida, para 2, comes to office due to 10 months of irregular vaginal bleeding. Her last menstrual period was 3 years ago. She has a history of hypothyroidism & takes levothyroxine daily. Ultrasound reveals thickened endometrium & a solid left adnexal mass. Endometrial biopsy is abnormal, & the patient requires surgery. Intraoperatively, the ovarian mass is yellow & firm. Pathology reports small cuboidal cells in sheets with gland-like structures containing acidophilic material. The cells are arranged in a microfollicular pattern around a pink, eosinophilic center. What is most likely secreted by this patient's tumor?

*Estrogen* - unopposed estrogen = hyperplasia of endometrial cells & glands Granulosa cell tuor = 5% of ovarian tumors = postmenopausal women = derived from ovarian stroma = sex cord-stromal tumors = small & cuboidal in shape = grow in cords or sheets = form follicle- or rosette-like structures (Call-Exner bodies) = gland-like appearance with pink eosinophilic center & coffee bean nuclei - theca cells = plump with lipid contents = yellow color on gross inspection = unilateral and large = *secrete estrogen* & can present with endometrial hyperplasia (postmenopausal bleeding with thickened endometrium on ultrasound)

Cervical biopsy reveals high-grade cervical intraepithelial neoplasia. What is the most likely finding on histopathology?

*Expansion of immature basal cells to epithelial surface* HPV: High-grade CIN - atypical cells have invaded beyond lower one-third of cervical epithelium (to epithelial surgace) - high rate of progression to cancer

23 yo man evaluated for 10 days of nonproductive cough, low-grade fever, headache, & malaise. Lung exam reveals scattered rales. Chest x-ray reveals bilateral patchy areas of consolidation. He has mild anemia & elevated serum lactate dehydrogenase level. Patient is treated for presumed Mycoplasma pneumoniae with azithromycin. Two months later, all of his symptoms & anemia have resolved. What best explains resolution of this patient's anemia?

*Fading of immune response* Mycoplasma pneumoniae = complement-mediated, intravascular hemolytic anemia via similarity between antigens in cell membrane of M pneumoniae & cell membrane of RBCs (I-antigen) - elevated levels of cross-reacting IgM Abs = cold agglutinins = ability to agglutinate RBCs in vitro at low temps = diagnosis After infection eliminated... - immune response against M pneumoniae has faded = concentration of cold agglutinins decreases & anemia resolves spontaneously

A randomized controlled study of 2000 patients with insomnia is conducted to evaluate the efficacy of a new medication to treat this condition. Ten subjects from both the control and treatment groups do not complete the study and are not included in the analysis. Study subjects in the treatment group are able to fall asleep an average of 5 minutes faster than study subjects in the control The difference is statistical significant (P=0.001). Subjects in neither group report an improvement in quality life. The investigators conclude that the new medication is efficacious in treating insomnia. These findings are most likely an example of which of the following types of error?

*Failure to distinguish between statistical significance and clinical significance* Study results... - "treatment group" able to fall asleep "5 minutes faster" than "control group" (p value of 0.001) - "statistically significant" does = 0.001 BUT new med makes you fall asleep only 5 minutes earlier than control group = not a big help for patient with insomnia = no help at all almost --> new med = clinically insignificant - investigators failed to distinguish between "statistical significance" and "clinical significance," & error by concluding new med is efficacious in treating insomnia

Patient presents with thrombosis in popliteal vein. The thrombosis most likely causes reduction of blood flow in what veins?

*Femoral* Popliteal vein drains blood into femoral vein

16 yo obese primigravida girl comes to ED in active labor. In an attempt to conceal pregnancy from her fam, patient did not receive prenatal care to take prenatal vitamins. Fetal heartbeat is undetectable, & she delivers stillborn boy via vaginal delivery. Exam of stillborn shows several dysmorphic features including closely set eyes & a midline mass consistent with proboscis. Fetal autopsy reveals fused cerebral hemispheres with absent forebrain fissure & single intracranial ventricle. What is the most likely mechanism for these findings?

*Field defect* = initial embryonic disturbance leads to multiple malformations by disrupting development of adjacent tissues & structures within particular region Holoprosencephaly (HPE) = via incomplete division of forebrain (prosencephalon) into 2 hemispheres - cleavage of prosencephalon into talencephalon & diencephalon occurs normally at 5 weeks gestation - combo of genetic (trisomy 13, sonic hedgehog gene mutations) & env'tal (maternal alcohol use) factors

Construction worker falls feet first from roof. He sustains a fracture of groove on undersurface of sustentaculum tali of calcaneus bone. What muscle tendons is most likely torn?

*Flexor hallucis longus* - tendon occupies first groove on posterior surface of talus & then groove on undersurface of sustentaculum tali

56 yo African American woman with history of HT is brought to ED because of three days of dysuria & back pain. On physical exam, she has temp of 39.2 C (102.6 F), BP of 70/40 mmHg, pulse of 130/min, & respirations of 28/min. She is confused & her skin is diffusely warm to touch. She has suprapubic & costovertebral angle tenderness, but no rashes or edema. Her complete blood count demonstrates leukocytosis with increased neutrophils, but is otherwise normal. Coagulation studies are normal. Her urinalysis is positive for leukocyte esterase & nitrites & has numerous bacteria. Several hours later she becomes increasingly hypoxic requiring mechanical ventilation. Her respiratory symptoms are most likely due to what pathologic conditions?

*Fluid accumulation in alveolar spaces* ARDS - fevers, hemodynamic instability, tachypnea, urinary tract infection evidnece Sepsis & pulmonary infections = two most common risk factors for ARDS Sepsis - cytokines circulate in response to infection --> activate pulmonary epithelium --> inflammatory response mediated by neutrophils --> capillary damage & leakage of protein & fluid into alveolar space

Genetic analysis shows that more recent isolates have single nucleotide deletion within lac operon DNA sequence. This genomic change is most consistent with what?

*Frameshift mutation* Single base deletion --> frameshift mutation = within coding region (exons) of gene = deletion or insertion of any nucleotides not multiples of 3 = change in reading frame during protein translation = production of entirely different protein that is often shorter than original due to formation of premature codon

70 yo man develops progressive disinhibition syndrome characterized by episodes of emotional outbursts, inappropriate use of language, and socially inappropriate behavior. What labeled structures is most likely damaged?

*Frontal lobe* = disinhibition and deficits in concentration, orientation, judgement - may have reemergence of primitive reflexes - left sided = apathy - right sided = disinhibition

Recognize point mutation that results in stop codon: Stem: The sequence of the human beta globin gene, with the three exons in bold capital letters is shown in the figure. The translation start codon ATG at position 154-156 and the translation stop codon TAA at position 1575-1577 are underlined. WHICH of the following mutations (circled) will most likely lead to beta Thalassemia?

*G --> A at position 246* By introducing G__A at position 246, you introduce a stop codon... before it was GTT, when you transcribe to mRNA its CAA. Now after the mutation its ATT, when you transcribe this you get UAA, which is a stop codon and thus stops transcribing the protein.

In an experiment, 3 L of isotonic saline are infused IV into healthy volunteer after multiple physiologic parameters are recorded. Serial BP measurements show increase in systolic & diastolic BP. Ultrasonography reveals increase in left ventricular volume & engorgement of inferior vena cava. Blood levels of peptide hormone have also increased compared to baseline. This hormone is most likely to increase what in this test subject?

*Glomerular filtration rate* IV infusion of isotonic saline = intravascular volume expansion with increase in intracardiac volume & filling pressures Myocardial wall stretch = release of endogenous peptide hormones: ANP, BNP from atria & ventricles - activate guanylate cyclase --> increased cyclic GMP Kidney - natriuretic peptides promote afferent glomerular arteriolar vasodilation & efferent constriction --> increased GFR --> increased natriuresis (sodium excretion) & diuresis (fluid excretion) - inhibit proximal tubular sodium reabsorption & renin secretion --> reduced Ang II & aldosterone = natriuresis & diuresis

Innervation of general sensation at tonsillar lining

*Glossopharyngela nerve* Lesion - loss of gag reflex (afferent limb) - loss of sensation in upper pharynx, posterior tongue, tonsils, middle ear cavity - loss of taste sensation on posterior third of tongue

Renal handling of substance X studied in 3 experimental settings using increasing concentrations of this drug. Glomerular filtration rate is kept constant at 100 mL/min. Following readings are observed: Substance X ~ Exp 1 ~ Exp 2 ~ Exp 3 Glomerular Filtration = 80 ~ 300 ~ 400 Urinary excretion = 0 ~ 100 ~ 200 Based on this data, renal handling of substance X is most similar to what molecules?

*Glucose* = filtered in glucose & reabsorbed completely in proximal tubule under normal serum concentrations - once glucose reaches its Tm of appx 375 mg/min, excess filtered load passes unabsorbed through tubules As substance X increases, its glomerular filtration also rises - low concentration (Exp 1) = X completely reabsrobed & no amount excreted in urine As concentration filtered load increases, substance X begins to spill into urine = there is a limit to rate at which it can be reabsorbed = *transport max (Tm)* = determined by capacity of transporters available for active reasborption Serum concentration at which glycosuria begins = threshold of glucose = 200 mg/dL

Woman experiences weakness when abducting & medially rotating thigh after accident. What muscle is most likely damaged?

*Gluteus minimus* or medius - abducts & rotates thigh medially

What NT is most likely to be directly impaired in a patient with tetanus?

*Glycine* C tetani - produces potent metalloprotease exotoxin (tetanospasmin) = deadly in nanogram quantities Toxin... - binds receptors on presynaptic membranes of peripheral motor neurons --> migrates to retrograde axonal transport to central inhibitor neurons in spinal cord & brain stem = prevents release of glycine & GABA (inhibitor NTs) --> increased activation of motor nerves = muscle spasms & hyperreflexia - C botulinum inhibits release of ACh = flaccid paralysis

What is found in the infarct zone of a previous MI during the 2nd week?

*Granulation tissue with neovascularization* 10-14 days - sudden cardiac death 12 days after MI likely due to ventricular arrhythmias

28 yo woman comes to office to establish care. She recently moved to NY to begin job as copy editor at major newspaper. She has no known medical problems. The patient is in monogamous relationship with her husband. She usually eats fast food for lunch, & she & her husband cook in the evenings. She goes to gym about once every 2 weeks. Patient's temp is 36.7 C (98 F), BP is 118/64 mmHg, pulse is 60/min, & respirations are 14/min. Her BMI is 24.6 kg/m^2. Physical exam is unremarkable. Lab results are within normal range. Counseling this patient regarding diet & exercise would be an example of what?

*Health promotion* WHO...Health promotion = enabling ppl to increase control over their health & its determinants - improve their own health - improving dietary habits - exercising regularly - abstaining from smoking - losing weight if needed - falls under *primary* prevention = preventing disease process from getting established

2 month old girl brought to clinic due to perinatal hepatitis B exposure. Her mother is 22 & immigrated to US shortly after giving birth. Pregnancy was complicated by maternal hepatitis B infection. However, mother received no prenatal or perinatal care & was not diagnosed with chronic hepatitis B until immigration process. Maternal HBsAg, HBeAg, & anti-HBc are all positive; anti-HBs is negative. Infant has not been evaluated previously & has not received any immunizations or other meds. She is exclusively breast fed & has been growing normally. Vitals are normal & physical exam is unremarkable. No hepatomegaly or jaundice is seen. The infant's lab results will most likely show what?

*HBeAg* - infected infants have high viral loads & HBeAg levels - infants enter immune-tolerant phase of chronic HBV infection = asymptomatic & normal/mildly elevated liver function tests - over time...high risk of progression to cirrhosis & HCC =90% wihtout treatment - administer hepatitis B vaccine & immunoglobulin as soon as possible!!! - infant exposed to HBV during delivery - mother-to-child transmission most commonly occurs during delivery, but transplacental infection may also occur - maternal viral load & HBeAg = strongest risk factors for infant infection - infants born to HBeAg-positive women = >90% chance of acquiring infection

What is the single most important factor for developing aortic dissection?

*HYPERTENSION* Aortic dissection - HT = intimal tears

34 yo man comes to ED due to facial injury. Reports getting hit on face during fistfight at a bar. Exam shows dark blue periorbital echhymosis on right side. Ophthalmic & neurologic exams are otherwise normal. After evaluation, patient is discharged home. Several days later, bruise becomes greenish in color. This change is best explained by activity of what enzyme?

*Heme oxygenase* - contained in macrophages & other cells - degrades heme into biliverdin, carbon monoxide, ferrous iron while consuming oxygen & electrons provided by NADH & NADPH-cytochrome P450 reductase = green - further reduced by enzyme biliverdin reductase to yellow pigment bilirubin --> transported to liver bound to albumin Hematoma - after traumatic injury - hemoglobin-containing RBCs escape into periorbital tissues --> bruise = purple or bluish color

63 yo man comes to ED due to abdominal pain. Physical exam shows abdominal tenderness without guarding or rebound. His lab test results are as follows: Hemoglobin = 8.9 g/dL Platelets = 134,000/mm^3 Total bilirubin = 6.3 mg/dL Lactate dehydrogenase = 740 U/L Haptoglobin = Low On further investigation, magnetic resonance angiography of abdomen reveals mesenteric vein thrombosis. Flow cytometry shows absence of CD55 on surface of RBCs. What is the most likely pathologic renal finding in this patient?

*Hemosiderosis* Paroxysmal nocturnal hemoglobinuria (PNH) = via complement-mediated hemolysis = via mutated phosphatidylinositol glycan class A (PIGA) gene, which helps synthesize glycosylphosphatidylinositol (GPI) anchor protein --> helps attach several cell surface proteins (CD55 decay accelerating factor, CD59 MAC inhibitory protein) that inactivate complement --> absence = uncontrolled complement-mediated hemolysis Manifestations = fatigue & jaundice via hemolytic anemia = elevated bilirubin & lactate dehdyrogenase, low haptoglobin, hemoglobinuria - thrombosis at atypical sites - pancytopenia - *iron deposition in kidney (hemosiderosis) = interferes with proximal tubule function = interstitial scarring & cortical infarcts*

25-year-old male hospitalized with suspected tetanus. He sustained a minor lower extremity wound one week ago. What is most important in making this patient's diagnosis?

*History & physical exam* - C tetni only found locally at wound into which it was inoculated - determine immunization status of patient & length of time since last tetanus vaccine - adults = booster every 10 years recommended - penetrating trauma - physical exam = masseter muscle spasms (trismus or lockjaw), facial grimacing (risus sardonicus), muscle spasms, extension of truncal muscles = opisthotonos

29 yo man comes to physician after discovering painless scrotal mass on self-exam. He also has increased sweating & heat intolerance. He has no significant past medical history. Physical exam shows enlarged nontender right testicle. Lab evaluation shows increased serum T4 & T3 concentrations. Scrotal ultrasound shows hypechoic mass within right testicle. The constellation of findings seen in this patient most likely suggests an elevation of what serum markers?

*Human chorionic gonadotropin* Testicular malignancy most likely secreting human chorionic gonadotropin (hCG) - normally produced by placenta - also produced by nonseminomatous germ cell tumors - *alpha subunits of hCG, TSH, LH, FSH are identical* - *beta subunits of hCG & TSH share significant sequence homology* - because of structural similarity, hCG can bind to TSH receptor - high circulating levels of hCG --> over-stimulates thyroid gland = paraneoplastic hyperthyroidism

Patient scheduled for lumbar puncture for CSF analysis. During this procedure, what anatomical landmarks helps locate optic site for needle insertion?

*Iliac crest* - spinal cord extends from medulla to inferior border of L1 in adults (L2/L3 in neonates & infants) Lumbar puncture = patient in recumbent or sitting position = accurate opening pressure measurement = L3/L4 or L4/L5 spaces L4 vertebral body = lies on line drawn between highest points of iliac crests = can be visually identified & confirmed by palpation

45 yo man comes to clinic due to 2 month history of progressive left arm clumsiness & weakness. Patient initially attributed his symptoms to left rotator cuff injury he sustained several years ago; however, he has recently developed problems with his gait. Patient's symptoms have interfered with daily activities such as bathing and dressing. He has had no recent injury, headaches, or bowel/bladder symptoms. On physical exam, there is reduced muscle strength in left upper extremity. Further evaluation with MRI reveals lesion involving corticospinal tract. What additional signs is most likely to be seen in this patient?

*Hyperactive deep tendon reflexes* UMN = anything above anterior horn UMN lesions = stroke or brain tumor = spastic paralysis, clasp-like rigidity, hyperreflexia (including clonus), upgoing plantar reflexes (Babinski sign) - via loss of descending inhibition over second-order neurons into anterior horn

38-year-old man presents to ED because he has been vomiting blood. Endoscopy reveals bleeding duodenal ulcer. During his hospitalization, he develops prolonged oliguria. Renal biopsy shows epithelial necrosis of tubules, tubulorrhexis, & intratubular casts. What is the most important complication during recovery phase of this patient's condition?

*Hypokalemia* Ischemic acute tubular necrosis: Initiating stage - often unnoticed Maintenance stage (oliguric stage) - if significant tubular damage occurs - 24-36 hours - urine output decreases - metabolic changes of acute renal failure manifests Recovery stage - if patient survives maintenance stage - after 1-2 weeks - vigorous diuresis - electrolyte balance altered because renal tubules cannot yet fully function - high volume, hypotonic urine --> decreased serum concentrations of K+, Mg, PO4, Ca - paient can become dehydrated

52 yo homeless man found unresponsive on street & brought to ED. Patient's past medical history is unknown. His temp is 36.2 C (97.2 F) & BP is 108/62 mmHg. He is unresponsive to verbal & tactile stimuli. An arterial blood gas analysis shows that partial pressure of oxygen in his arterial blood is 60 mmHg. The partial pressure of oxygen in his alveoli is calculated to be 71 mmHg. What is the most likely cause of this patient's symptoms?

*Hypoventilation* = common in patients with suppressed central respiratory drive (sedative overdose, sleep apnea) or those with diseases that decrease inspiratory capacity (MG, obesity) - partial pressure of oxygen in alveoli is normally 104 mmHg - partial pressure of oxygen in arterial blood (PaO2) = normally around 100 mmHg - healthy individuals: A-a gradient = between 5-15 mmHg This patient = low PaO2 & PAO2 - normal A-a gradient = 71-60 = 11 - low PaO2 directly due to his low PAO2 & not caused by V/Q mismatch or O2 diffusion impairment Possible causes of hypoxemia in setting of normal A-a gradient = alveolar hypoventilation = inspiration of air at high altitude

24 yo Caucasian male admitted to hospital with one-week history of fever, cough, & chest pain. Lung ausculatation reveals crackles over right lower lung lobe. When placed in upright glass tube, his anticoagulated red blood cells fall at rate of 35 mm per hour. This finding is most likely related to what substance?

*IL-6* Injury... - local neutrophils & macrophages release TNF-alpha, IL-1, IL-6 into circulation = systemic inflammatory response Acute-phase reactants increase = fibrinogen, ferritin, C-reactive protein, serum amyloid A, serum amyloid P, complement factors - bind to microbes & fix complement - increased --> erythrocytes stack = rouleaux = sediment faster than individual RBCs = ESR = non-specific marker of inflammation

13 yo boy comes to office for postop follow-up. He was seen in ED 3 weeks earlier with acute abdominal pain & was found to have acute appendicitis. Patient underwent urgent appendectomy without any apparent immediate complications and was released home. Several days later, he started having burning pain at surgical scar radiating to suprapubic region but otherwise feels well. Exam shows healed surgical incision centered over McBurney point. There is loss of sensation over right suprapubic area. The cremasteric reflex is normal. What nerves is most likely injured in this patient?

*Iliohypogastric* nerve - arises from L1 nerve root - emerges from lateral border of upper psoas major --> passes behind kidney anterior to quadratus lumborum = motor function to anterolateral abdominal muscles = anterior branch emergency above superficial inguinal ring to innervate skin above pubic region = lateral branch descend over iliac crest to innervate gluteal region Can be injured during appendectomy = decreased sensation at suprapubic region

If acetabulum is fractured at its posterosuperior margin by dislocation of hip joint, what bones could be involved?

*Ilium* Acetabulum = cup-shaped = lateral side of hip bone = formed superiorly by *ilium, posteroinferiorly by ischium, & anteromedially by pubis*

Echocardiogram shows severe aortic regurgitation as a sequela to prior infection. What changes is most likely responsible for maintaining cardiac output in the setting of this valvular abnormality?

*Increase in left ventricular stroke volume* Chronic severe aortic regurgitation - regurgitant blood flow increases left ventricular end-diastolic volume (preload) & wall stress = eccentric hypertrophy --> increases stroke volume & maintains cardiac output

Within the true pelvis, the surgeon can most likely palpate the right ureter immediately anterior to what structures?

*Internal iliac artery* Ureters - course inferiorly toward bladder within retroperitoneum just anterior to psoas muscles - lie medial to ovarian vessels & *anterior to internal iliac artery* Uterine artery crosses over anterior surface of ureter (water under bridge)

17 yo boy brought to office for evaluation of bilateral breast enlargement. He first noticed it a few months ago and says that it is slightly painful. His parents are concerned that his breasts are gradually becoming more prominent. The patient is in special education classes due to long-standing history of learning disabilities. His father has type 2 DM & is on dialysis for chronic renal failure. Height is at 95th percentile, & weights is at 25th percentile for age & sex. Symmetrical glandular tissue is palpated under both nipple-areolar complexes. His sense of smell is normal, & his testices are small & firm. Lab evaluation would most likely show what?

*Increased FSH* Klinefelter syndrome = sex chromosome aneuploidy = 47,XXY = atrophies hyalinized seminiferous tubules = low inhibin levels & damaged Leydig cells = low testosterone - lack of feedback = excess gonadotropins = increased LH & FSH = increased estrogen = gynecomastia

Most likely cause of polycythemia vera

*Increased bone marrow sensitivity to growth factors* Polycythemia vera = clonal myeloproliferative disease of pluripotent hematopoietic stem cells = *V617F mutation involving JAK2 gene --> replaces valine with phenylalanine at 617 position = hematopoietic cells more sensitive to growth factors such as erythropoietin & thrombopoietin* = increased RBC mass, increased plasma volume, & low erythropoietin levels = elevated platelet &/or WBC count = thrombotic events = peptic ulcerations & pruritus (histamine release from basophils) = gouty arthritis (increased cell turnover) = plethoric, ruddy face & splenomegaly - treatment = serial phlebotomy to keep hematocrit < 45%

36 yo man comes to office due to 2 month history of pruritic skin rash over elbows & knees. Patient has been using skin emollients, but lesions have not improved. He also has prolonged history of episodic abdominal discomfort, flatulence, & voluminous greasy stools. Cardiopulmonary exam is normal. Abdomen is soft & nontender. Skin exam shows papulovesicular rash in groups with erosions & excoriations. What is most likely to be seen in this patient?

*Increased intestinal intraepithelial lymphocytes* Dermatitis herpetiformis (DH) = microabscesses containing fibrin & neutrophils at dermal papillae tips - overlying basal cells become vacuolated, & coalescing blisters form tips of involved papillae - IgA Abs against gliadin --> cross-react with epidermal transglutaminase - strongly associated with celiac disease = *increased intraepithelial lymphocytes*, variable loss of villus height, crypt hyperplasia = malabsorption

7 yo boy brought to office by his mother due to "facial puffiness," which is especially noticeable in morning. He has history of mild intermittent asthma that is well controlled with albuterol as needed. His temp is 36.1 C (97 F), BP is 98/62 mmHg, & pulse is 89/min & regular. Physical exam shows bilateral lower extremity pitting edema. Nephrotic-range proteinuria consisting mainly of albumin is revealed on urine analysis. What mechanisms explains this patient's lab findings?

*Increased selective filtration of proteins* Child with volume overload (facial puffiness, edema) + nephrotic-range proteinuria that is mainly albumin = minimal change disease = systemic T cell dysfunction = glomerular permeability factor = cytokine that causes podocyte foot process fusion, decreased anionic properties of GBM - loss of negative charge = selective loss of albumin in urine = selective albuminuria

32 yo Caucasian woman experiences three episodes of deep venous thrombosis in a six year period. She has a history of pulmonary embolism as well. The patient's partial thromboplastin time (PTT) is within normal limits, & remains unchanged when activated protein C is added to her plasma. The most likely cause of this patient's problem is:

*Inherited* - inherited causes of hypercoagulability must be considered in all patients under age 50 who present with thromboses in absence of any obvious explanation for acquire prothrombotic state - patient's plasma = resistant to normally antithrombotic effects of activated protein C Mutation in Factor V gene = factor Va resistant to inactivation by activated protein C = 2-15% of Caucasians carry specific factor V mutation/Leiden mutation

What is the most likely cause of a patient's shortness of breath in Alpha-1 Antitrypsin Deficiency

*Interalveolar septa destruction* AAT deficiency - autosomal codominant - affects lungs & liver - most ppl homozygoud for Z allele - severe panacinar emphysema - cirrhosis = 2nd most common cause of death in this pop - *globules stain reddish-pink with periodic acid-Schiff reaction* & resist digestion by diastase (enzyme that breaks down glycogen)

Saphenous vein removed & grafted to one of diseased coronary arteries to bypass its atherosclerotic narrowing. The vein used as a graft during this patient's procedure can be accessed at what sites?

*Just inferolateral to pubic tubercle* Great saphenous vein = superficially in leg = longest vein in body = courses superiorly from medial foot, anterior to medial malleolus, & up medial aspect of leg & thigh - surgeons access great saphenous vein in medial leg or, less commonly, near its point of termination in femoral triangle of upper thigh

28 yo man comes to physician with muscle weakness & headaches for last 2 months. He denies palpitations, tremors, or increased sweating. His BP is 190/120 mmHg & his pulse is 68/min. His serum potassium level is 2.8 mEq/L. The patient's serum plasma renin activity is high & his serum aldosterone levels are elevated. A 24-hour urine collection shows increase potassium excretion. What is the most likely cause of this patient's symptoms?

*Juxtaglomerular cell tumor* = rare, small, solitary, benign juxtaglomerular cell neoplasms Hyperaldosteronism: Secondary hyperaldosteronism = overproduction of aldosterone *secondary to increased renin synthesis* = elevated levels of both renin & aldosterone Causes of secondary hyperaldosteronism = *renal artery stenosis (fibromuscular dysplasia, atherosclerosis), diuretic use, malignant HT, renin-secreting tumors*

45-year-old man brought to ED after being outdoors in Rocky Mountains for 10 days. He has had a 5-kg (11-lb) weight loss during this period. His serum glucose concentration is 92 mg/dL. A serum glucose concentration within the reference range was most likely maintained in this patient via glucose synthesis in the liver and in what organs?

*Kidney* - renal release of glucose into circulation = result of glycogenolysis and gluconeogenesis = breaking down and formation of glucose-6-phosphate from precursors (lactate, glycerol, AAs) - normally retrieve as much glucose as possible = urine glucose free - glomeruli filter from plasma appx 180 grams of D-glucose per day = all reabsorbed through glucose transporter proteins that are present in cell membranes within proximal tubules

34 yo woman with polycystic ovary syndrome comes to office with her husband for treatment of infertility. Patient has been unable to conceive despite having unprotected sexual intercourse several times a week for past 2 years. Her menses are irregular & occur every 2-3 months, consistent with chronic anovulation. She does not use tobacco, alcohol, or illicit drugs. Patient takes no meds & has no allergies. BMI is 32 kg/m^2. Physical exam shows coarse hair on her chin & abdomen. Patient is initially prescribed clomiphene therapy with short course of menotropins followed by single injection of hCG. The use of hCG therapy primarily mimics what physiologic events?

*LH surge* - high estrogen levels in late follicular phase have positive feedback effect on LH = LH surge --> rupture of dominant follicle = extrusion of ovum (ovulation) Failure of ovulation (anovulation in polycystic ovary syndrome) = common cause of infertility - treatment = drugs that act like FSH & LH Menotropin = human menopausal gonadotropin = mimics FSH & triggers formation of dominant ovarian follicle *When follicle appears mature, exogenous hCG is administered* - alpha subunit of hCG = structurally similar to LH --> stimulates LH surge by inducing ovulation

Patient with hereditary blood clotting problems presents with pain in the back of her knee. An arteriograph reveals blood clot in popliteal artery at its proximal end. What arteries will allow blood to reach the foot?

*Lateral circumflex femoral* Proximal end of popliteal artery blocked... - blood may reach foot via *descending branch of lateral circumflex artery* = anastomosis around knee joint

66 yo man comes to hospital due to sudden onset of chest pain & dyspnea. Patient has history of asthma & GERD but says his current symptoms "don't feel like my usual stomach or lung problems." An ECG is consistent with ST-elevation MI, & emergent cardiac catheterization is performed. Evaluation of his left & right coronary arteries shows left dominant circulation with normal left main coronary artery. A stenotic region is identified in one of the other coronary vessels. During percutaneous intervention on culprit lesion, a small thrombus detaches & moves forward, causing obstruction of artery supplying atrioventricular node. Atherosclerosis of what arteries most likely caused the MI in this patient?

*Left circumflex artery* Coronary dominance determined by coronary artery that supplies blood to posterior descending artery (PDA / Posterior Interventricular Artery) - right coronary artery = 70% = right dominant - left circumflex artery = 10% of population = left dominant - both right coronary & left circumflex artery = 20% of pop = codominant - AV nodal artery most often arises from dominant coronary artery

23 yo previously healthy man brought to ED after stab injury. His friends report guy jumped out in front and stabbed him in chest. Physical exam shows laterally directed anterior chest wall stab wound at fifth intercostal space along left midclavicular line. What structures is most likely to have been injured in this patient?

*Left lung* - penetrating, laterally directed stab wound in 5th ICS at midclav = left lung

64 yo man with type 2 DM is evaluated in clinic due to occasional dizziness. His symptoms usually occur while playing tennis. Patient has not had any falls or loss of consciousness. He has no known history of coronary artery disease or stroke. Patient has smoked a pack of cigarettes daily for past 40 years & occasionally drinks alcohol. Orthostatic vital signs are normal. ECG shows normal sinus rhythm. Doppler ultrasound evaluation of left vertebral artery reveals retrograde (caudal) flow instead of normal antegrade flow. What arteries is most likely to be occluded based on these ultrasound findings?

*Left subclavian* Subclavian steal syndrome = via hemodynamically significant stenosis of subclavian artery proximal to origin of vertebral artery Subclavian stenosis = via atherosclerosis - lowered distal subclavian arterial pressure --> reversal in blood flow (steal) from contralateral vertebral artery to ipsilateral vertebral artery, away form brainstem - when symptoms do occur, typically related to arm ischemia in affected extremity (exercise-induced, fatigue, pain, paresthesias) or vertebrobasilar insufficiency (dizziness, vertigo, drop attacks) - physical exam can show: difference (>15 mmHg) in brachial systolic BP between affected arm & normal arm - doppler ultrasound of cerebrovascular & upper extremity arterial circulation = diagnosis in most patients

66-year-old man comes to physician because of a 2-month history of inability to maintain an erection. He also has had fatigue and difficulty sleeping and concentrating during this period. Three months ago, he had a cerebral infarction with right hemiparesis that has gradually resolved. Physical exam shows no abnormalities. What additional pairs of findings in this patient is most likely on history taking? Libido = Nocturnal erection =

*Libido = decreased* *Erections = normal* - libido decreased due to depression - nerves are intact, so normal nocturnal erections Strokes in elderly are associated with depression

5 week old girl brought to ED with several hours of fever, irritability, & vomiting. She awoke this morning warm to touch & refusing to drink. Her temp is 40.1 C (104.2 F). Lumbar puncture reveals CSF pleocytosis; additional fluid is sent for Gram stain & culture. Empiric cefotaxime therapy is initiated. However, no clinical improvement is seen. CSF culture yields organism that is resistant to cefotaxime. What organisms is most likely causing this patient's infection?

*Listeria monocytogenes* - not adequately covered by third-generation cephalosporins *cefotaxime, ceftriaxone) = gram-positive bacillus = factultative intracellular = cell-mediated immunity needed to clear it = *most common among patients with deficient cell-mediated immunity, such as infants, those receiving chemo due to altered penicillin-binding proteins* - susceptible to *amipicillin* = added to empiric treatment of meningitis in young infants or immunocompromised patients

56 yo man hospitalized in ICU being evaluated for fever. He was admitted 8 days ago with respiratory failure & has had complicated hospital course, including mechanical ventilation, central venous line placement, & broad-spectrum antibiotic therapy. Patient has history of HIV & a hematologic malignancy. His last chemo session was 2 weeks ago. Chest x-ray does not reveal new infiltrate, & urine cultures are negative for infection. Blood cultures grow pseudohyphae-producing yeast species with ability to form germ tubes. What most likely directly contribute to development of fungemia in this patient?

*Low neutrophil count* Candidemia = single-celled budding yeast with pseudohyphae Neutrophils = prevent hematogenous spread of Candida Disseminated candidiasis = candidemia, endocarditis So.... - local defense against Candida performed by T cells --> common in patients who have HIV - systemic infection prevented by neutrophils --> neutropenic patients more likely to have systemic form of disease

56 yo woman brought to ED due to 2 day history of high fever, headache, mild confusion, & dry cough. She also has mild abdominal discomfort & watery diarrhea. Patient recently returned from cruise to Hawaii. Her other med problems include HT & hyperlipidemia. She has smoked 1 pack of cigarettes daily for 20 years. Her temp is 40 C (104 F), BP is 104/63 mmHg, pulse is 85/min, & respirations are 24/min. Lung exam reveals lower lobe crackles with no wheezing. Her abdomen is soft, non-distended, & non-tender. Chest x-ray shows bilateral lower lobe interstitial infiltrates. What additional findings is most likely to be present in this patient?

*Low serum sodium* Legionellosis: Legionnaires' disease - recent exposure to contaminated water (sporadic cases or common-source outbreaks in cruise ships, spas, hospitals, air-conditioned hotels) - radiographic evidence = patchy infiltrates that progress to consolidation - high fever (>39 C [102.2 F]) - relative bradycardia - neuro symptoms = confusion, headache - GI symptoms = diarrhea Gram stain = many neutrophils but few or no organisms - diagnosed by urinary antigen testing - grows on selective medium = buffered charcoal yeast extract [BCYE] - *most common lab abnormality = hyponatremia*

Nephrology researcher conducts clinical study to determine risk factors for dev't of renal calculi. He recruits number of patients with history of idiopathy calcium oxalate kidney stones, & age- & sex-matches healthy individuals. Detailed medical, surgical, & nutritional histories are obtained, & several serum & urine lab tests are performed. What is most likely to be seen in affected patients compared to healthy individuals in this study?

*Lower urinary citrate* Hypercalciuria Hyperoxaluria Hyperuricosuria Hypocitraturia = increased risk for calcium oxalate ppt & stone formation = often occurs in setting of chronic metabolic acidosis (distal renal tubular acidosis, chronic diarrhea) via enhanced renal citrate reabsorption

Persistent lymphedema presidposes to this. May arise appx 10 years after radical mastectomy with axillary lymph node dissection for breast cancer.

*Lymphangiosarcoma*

2 yo boy being evaluated for failure to thrive & developmental delay. His past med history is significant for recurrent ear infections since age 6 months. Physical exam shows coarse facial features, corneal clouding, hepatosplenomegaly, & restricted joint mobility. Mass spectrometry analysis is performed on cultured fibroblasts & reveals deficient phosphorylation of mannose residues on certain glycoproteins in the Golgi apparatus. Normally, these proteins are most likely to be transported to what cellular locations?

*Lysosome* I-cell disease - AR - lysosomal storage disorder - defect in protein targeting - proteins targeted for lysosomes are modified differently than those destined for extracellular location - Golgi body phosphotransferase enzyme catalyzes phosphorylation of mannose residues on lysosome-bound proteins = traverse Golgi network & transported to lysosome

62 yo woman comes to physician with cough & dyspnea. She expectorates copious amounts of pale tan-colored fluid. Chest x-ray reveals pulmonary infiltrate that is subsequently biopsied. Histological exam shows columnar mucin-secreting cells that line alveolar spaces without invading stroma or vessels. This patient's condition is best categorized under what disease processes?

*Malignant neoplasm* Adenocarcinoma in situ / Bronchioalveolar carcinoma - most common type of lung cancer in US - arises form alveolar epithelium - located at periphery of lung - preinvasion lesion - *growth along intact alveolar septa* without vascular or stromal invasion - well-differentiated, dysplastic columnar cells with or without intracellular mucin - mucinous forms can result in production of copious amounts of watery sputum (bronchorrhea) - has tendency to undergo aerogenous spread & can progress to invasive disease if not resected

Linear skull fracture at junction of frontal, parietal, temporal, & sphenoid bones is seen on head CT scan. A branch of what arteries is most likely severed in this patient?

*Maxillary* Fracture at pterion = where frontal, parietal, temporal, & sphenoid bones meet in skull = thin = risked laceration of middle meningeal artery = epidural hematoma Middle meningeal artery = branch of maxillary artery! = one of terminal branches of external carotid artery = enters skull at foramen spinosum = supplies dura matter & periosteum

Med student conducting chart review of patients admitted through ED with pancreatitis. As part of descriptive analysis, blood glucose levels of 800 patients with acute pancreatitis were found to have strongly positive skewed distribution. What is most consistent with this finding?

*Mean is greater than median* Positively skewed distribution = mean shifted in positive direction (to right), followed by median & then mode

Highly agitated 54 yo man brought to ED by his fam because he is unable to effectively communicate. He speaks clearly & with conviction but his sentences are incomprehensible. He does not appear to understand the doc's questions, does not follow oral or written instructions, & cannot repeat simple phrases. Branch occlusion of what arteries is most likely responsible for this patient's condition?

*Middle cerebral artery* Fluent aphasia = fluent, well articulated, melodic - but meaningless - cannot understand verbal or written language - no awareness of cognitive deficit - lesion in Wernicke's area = in auditor association cortex with posterior portion of superior temporal gyrus in dominant (left) temporal lobe - inferior terminal MCA branches supply Wernicke's area

10 yo boy falls from tree house. Resultant heavy compression of sole of his foot against the ground caused fracture of head of talus. What structures is unable to function normally?

*Medial longitudinal arch* - keystone = head of talus = at summit between sustentaculum tali & navicular bone = supported by spring ligament & tendon of flexor hallucis longus muscle

56 yo smoker with persistent dry cough comes to physician due to recent-onset headaches & dyspnea. He also complains of having a "puffy face" for 2 weeks but denies any other med problems. He has no shoulder pain. Physical exam shows symmetrical facial swelling & conjunctival edema. His pupils are equal, round, & reactive to light. Dilated vessels are seen over his neck & upper trunk. Hears sounds are clear. This patient's condition is most likely caused by what?

*Mediastinal mass* - impaired venous return from upper body SVC syndrome - dyspnea, cough, swelling of face, neck, & upper extremities - headaches, dizziness, confusion via cerebral edema & elevated ICP - dilated collateral veins may be seen in upper torso - lung cancer, followed by non-Hodgkin lymphoma = most common cause of SVC syndrome Intrathoracic spread of bronchogenic carcinoma may = compression of SVC

5 yo Caucasian boy brought to physician's office with recent-onset gait instability and gait ataxia. MRI of brain shows midline posterior fossa mass. Biopsy of mass reveals sheets of primitive cells & many mitotic figures. This patient most likely suffers form what?

*Medulloblastoma* - sheets of primitive cells with many mitotic figures - part of group: primitive neuroectodermal tumors (PNETs) = undifferentiated & aggressive - cerebellar vermis = most common location - increased intracranial pressure & cerebellar dysfunction - both pilocytic astrocytomas & medulloblastomas arise in cerebellum --> must use microscopic findings! PNETs = sheets of small cells with deeply basophilic nuclei & scant cytoplasm (small, round, blue cells)

64 yo man comes to office due to 4 weeks of progressive dyspnea. For past several months, he has had nonproductive cough & felt fatigued. His medical problems include degenerative joint disease & peptic ulcer disease. He has smoked 2 packs of cigarettes daily for 38 years but quit 4 years ago. On exam, there are decreased breath sounds & percussive dullness at base of right lung. Chest CT scan reveals right-sided pleural effusion & diffuse nodular thickening of pleura. On thoracocentesis, bloody fluid is obtained. Pleural biopsy shows proliferation of epitheloid-type cells that are jointed by desmosomes, contain abundant tonofilaments, & are studded with very long microvilli. What is the most likely diagnosis?

*Mesothelioma* - asbestos = primary risk factor - hemorrhagic pleural effusion frequently seen - nodular or smooth pleural thickening = main finding - histopathology = tumor cells with numerous, long slender microvilli & abdundant tonofilaments - immunohistochemical markers = pancytokeratin

What ultrastructural changes would most likely indicate irreversible myocardial cell injury in a patient?

*Mitochondrial vacuolization* Irreversible injury = vacuoles + phospholipid-containing amorphous densities within mitochondria = permanent inability to generate further ATP via oxidative phosphorylation

6 yo boy brought to ED due to bleeding after dental extraction earlier this morning. Patient's past med history is significant for painful swelling of his knee joints after minor trauma. Aspiration of joints during several occasions yielded frank blood, & he was diagnosed with hemarthrosis. He has no known allergies. Currently, hemostasis in this patient most likely can be achieved by admin of what?

*Thrombin* = clotting Hemophilia = X-linked Factors VIII & IX = intrinsice coag pathway --> activate factor X --> catalyzes conversion of prothrombin (factor II) into thrombin in common pathway

44 yo man with progressive dyspnea is diagnosed with dilated cardiomyopathy. Despite optimal med therapy, he continues to have symptoms & disease progression is noted. He undergoes cardiac transplantation after suitable donor becomes available. Permission is obtained from patient to study his diseased heart for intracellular calcium regulation. Microelectrodes placed into cardiac muscle cells detect rapid decrease in cytoplasmic calcium level immediately preceding relaxation. What proteins is most likely responsible for the observed change in electrolyte levels?

*Na+/Ca2+ exchanger* Final stage of excitation-contraction couple = myocyte relaxation = subsequent to calcium efflux from cytoplasm - intracellular calcium removed primarily via Na+/Ca2+ exchange pump (NCX) & sarcoplasmic reticulum Ca2+-ATPase pump (SERCA) So... Cacium efflux from cardiac cells prior to relaxation primarily mediated via Na+/Ca2+ exchange pump & sarcoplasmic reticulum Ca2+-ATPase pump

6 yo boy brought to ED by parents due to persistent nasal bleeding. Boy picks his nose frequently and has several nosebleeds in past, all of which stopped spontaneously after pinching nose. Parents say they have been pinching nasal alae for over 30 mintutes while boy leans forward. Fam history is negative for bleeding disorders. Patient takes no meds and has no allergies. Exam shows continuous blood trickle from right nostril. Silver nitrate cautery is performed and bleeding stops. Cautery was most likely applied to what location in nasal cavity?

*Nasal septum* - anterior nosebleeds = most common = in vascular watershed area of nasal septum (anteroinferior part of nasal septal mucosa) = Kiesselbach plexus Anastomosis = septal branch of anterior ethmoidal artery = lateral nasal branch of sphenopalatine artery = septal branch of superior labial artery (branch of facial artery) Management = compression of nasal alae to stop bleeding from Kiesselbach plexus - cautery = silvery nitrate

2-year-old Caucasian boy has spontaneous bursts of non-rhythmic conjugate eye movements in various directions. He also suffers from hypotonia & myoclonus. Careful physical exam reveals abdominal mass. What is the most likely diagnosis of his abdominal mass?

*Neuroblastoma* - non-rhythmic conjugate eye movements associated with myoclonus = opsoclonus-myoclonus syndrome - young children - most common extracranial childhood cancer - develops from neuroblasts in adrenal medulla - increased number of copies of N-myc gene

41 yo man with Down syndrome evaluated in clinic due to congitive decline. Cognitive functions have become progressively impaired in past several years. He previously volunteered at community library but recently lost his position as he could no longer perform his duties. Patient is now completely dependent on caregiver for assistance with his activities of daily living such as getting dressed, bathing, & using toilet. His caregiver reports that patient keeps wondering in group home & has become lost on several occasions. What is most likely to be increased in this patient?

*Neuronal amyloid precursor protein* Down syndrome: Early-onset Alzheimer dementia (AD) - after age 35 - accumulation of neurofibrillary tangles - extracellular amyloid-beta (Abeta) plaque - tau protein hyperphosphorylated --> microtubule structures collapse into "tangles" = global neuronal dysfunction

86 yo woman hospitalized for UTI due to E coli & is being treated with ceftriaxone. She has history of advanced dementia, coronary artery disease, & CHF. On fifth day of hospitalization, she seems agitated. Nurse also reports that the patient had 3 episodes of diarrhea the previous night. Her temp is 38.3 C (101 F). In addition to appropriate hand hygiene, what equipment is necessary before examining this patient?

*Nonsterile gloves & gown* C difficile infectoin - contact precautions - soap & water handwashing - gown for any patient contact - nonsterile gloves that should be changed after contact with contaminated secretions - dedicated stethoscope & BP cuff should be left in patient's room

Diarrheal outbreak is reported at private school in Columbus, Ohio. Six healthy children age 10-11 & two teachers developed acute vomiting & diarrhea within 2-day period. They describe diarrhea as watery & without blood or mucus. Three of those affected are febrile during their illness. None of the patients have traveled abroad recently, & all are up to date with immunizations. Stool test results are pending. What pathogens is most likely cause of the illness?

*Norovirus* = most common cause of viral gastroenteritis = diarrhea, vomiting, fever, malaise, headache - diarrhea = watery without blood or mucus via lack of small bowel inflammation = Calicivirus fam = linear, nonenveloped, single-stranded RNA genome = resistant to inactivation by acid, bile, & pancreatic enzymes = fecal-oral spread = outbreaks - Rotavirus unlikely in children who as vaccinated or adults who likely have Ab protection from exposure during childhood

Bacteria expresses a lipopolysaccharide on their outer membrane surface that stimulates toll-like receptors in inflammatory cells. This in turn leads to degradation of lkB inhibitor protein, which normally binds to latent transcription factor found in cytoplasm. What factors is most likely to be directly activated by removal of this inhibitor protein?

*Nuclear factor-kappa B* = fam of transcription factors - in inflammatory cells, it is normally present in latent, inactive state bound to its inhibitor protein, lkB Classical activation pathway - extracellular signal, such as binding of bacterial antigens to toll-like receptor = activation of lkB kinase --> ubiquination & subsequent destruction of lkB with release of free NK-kB --> NF-kB enters nucleus & promotes synthesis of number of inflammatory proteins such as cytokines, acute phase reactants, cell adhesion molecules, leukocyte-related growth factors

45 yo man with endstage polycystic disease undergoes decreased-donor kidney transplantation. His postoperative course is unremarkable with normal functioning of renal allograft. Four yeast later, patient develops HT. Lab studies show progressive increase in serum creatinine levels over last few months. Urinalysis is within normal limits. On ultrasonography, transplanted kidney is reduced in size. A biopsy of graft is most likely to show what?

*Obliterative vascular fibrosis* Chronic renal allograft rejection - gradual deterioration in graft function = at least 3 months post-transplant in absence of other precipitating events = worsening HT, progressive rise in creatinine, proteinuria with normal urinary sediment = fibrous intimal thickening & scattered mononuclear infiltration of surrounding tissues - chronic renal ischemia & chronic inflammation = shrinking of renal parenchyma with tubular atrophy & interstitial fibrosis

Kidney biopsy samples from 500 diabetic patients were examined by several pathologists. Pathologists that knew the diabetes status of patients were three times more likely to interpret sample microscopy findings as "diabetic nephropathy." What most likely explains the difference in interpreting the microscopy results?

*Observer bias* = when investigator's decision is affected by prior knowledge of exposure status - pathologists were prejudiced by clinical history because they knew that diabetic nephropathy is a common finding in patients with diabetes

44 yo man has following findings on pulmonary function testing Predicted ~ Patient values FRC (L): 3.2 ~ 4 Residual Volume (L): 1.5 ~ 3 TLC (L): 5.9 ~ 6.8 FEV in 1 sec (L): 3.5 ~ 2.0 FEV1/forced vital capacity: 75% ~ 53% FEF (25-75%): 4.4 ~ 1.2 This pattern of pulmonary function represents what?

*Obstructive lung disease only*

A 45-year-old woman with multiple sclerosis is brought to the emergency department by a friend because of a 1-hour history of increasing confusion; she is now stuporous. She has been in remission for 2 years. Her temperature is 37.2'C (99 degrees F), pulse is 72/min, respirations are 8/min, and blood pressure is 116/66 mm Hg. Percussion of the chest shows decreased lung volumes. The lungs are clear to auscultation. Breath sounds are distant There is a minimal gag response. When amused, she is mildly combative, moves all four extremities, and then drift back into stupor. Arterial blood gas analysis on room air shows: pH 7.12 Paco2 76 mm Hg Po2 50 mm Hg Which of the following is the most likely cause of this patients condition?

*Opioid overdose* PAO2 = 150 - PaCO2 / [0.80] PaCO2 = 76 PAO2 = 150 - (76 / 0.8) = PAO2 = 150 - 95 = 55 = PAO2 PAO2 = 55 - PaO2 = 55 - 50 = 5 QUICK: Respiratory depression = OPIOIDS! normal respiratory rate = 12-20 breaths/min

56 yo patient with lung cancer hospitalized with confusion & fatigue. Her initial lab studies show: Serum sodium = 118 mEq/L Serum potassium = 4.3 mEq/L BUN = 40 mg/dL Serum creatinine = 1.3 mg/dL Calcium = 12 mg/dL Blood glucose = 198 mg/dL If her electrolyte abnormalities were corrected to quickly to the normal values she would most likely develop?

*Osmotic demyelination syndrome* Rapid correction of chronic hyponatremia - quadriplegia via demyelination of corticospinal tracts - pseudobulbar palsy via demyelination of corticobulbar tracts of CN IX, X, XI Pseudobulbar palsy - head & neck muscle weakness, dysphagia, dysarthria - pseudo bc nuclei of corresponding CNs remain intact - contrast: rapid correction of hypernatremia = cerebral edema

48 year old woman comes to physician because of 3-month history of fatigue, weakness, loss of appetite, and weight loss. Her serum parathyroid hormone concentrations are increased. X-rays of skeletal system show generalized osteopenia, with subperiosteal resorption of bone within phalanges. What mechanisms is the most likely cause of the skeletal changes observed in this patient?

*Paracrine stimulation of osteoclasts by osteoblasts* - describes how PTH acts on bone to cause resorption - acts on osteoblasts to produce RANKL, which then binds to RANK receptor on osteoclasts to cause resorption

41 yo man was involved in fight & felt weakness in extending knee joint. On exam, he was diagnosed with lesion of femoral nerve. What symptoms would be a result of this nerve damage?

*Paralysis of vastus lateralis* Femoral nerve innervates - quadratus femoris - sartorius - vastus muscles

18 month old boy brought to physician by his parents for fever, runny nose, & sore throat. Physician reassures parents & recommends supportive care with plenty of fluids. He sends them home with instructions to follow up if boy's symptoms worsen. Two days later, infant is brought to ED with persistent fever, brassy cough, & difficulty breathing. Physical exam reveals stridor. What pathogens is most likely resopnsible for this patient's condition?

*Paramyxovirus* - brassy, barking cough & breathing difficulties = acute laryngotracheitis (croup) - dyspnea associated with croup via inflamed subglottic tissue obstructing upper airway - most common cause of croup = parainfluenza

10-year-old immigrant from Eastern Europe brought to office due to exertional dyspnea & fatigability. Boy tires easily when walking & cannot keep up with his peers at playground. According to parents, he was diagnosed with congenital heart disease in infancy, for which they refused treatment. They cannot recall details of diagnosis. Patient also has had occasional respiratory infections throughout childhood that have not required hospitalization. He takes daily multivitamin & no meds. He has received only a few childhood vaccinations based on parental preference. Patient has no fam history of heart disease. Physical exam shows toe cyanosis & clubbing but no finger abnormalities. All extremity pulses are full & equal. What is the most likely diagnosis?

*Patent ductus arteriosus* - small = continuous, machinelike murmur (left-to-right shunting) - large = can present any time during childhood = progressive pulmonary HT & reversal of shunt to right-to-left Consequences = heart failure (shortness of breath, fatigability) - cyanosis (Eisenmenger syndrome) - cyanosis & clubbing most pronounced in lower extremities (differential) because PDA delivers unoxygenated blood distal to left subclavian artery - tetralogy of fallot would be whole-body cyanosis

30 yo man develops urinary incontinence 2 weeks after successful treatment of fracture of left pelvis that was sustained at work. He was pinned against loading dock by truck moving in reverse. Physical exam shows distended bladder. Cytometrography shows absence of micturition reflexes. After bladder fills to capacity, overflow of urine occurs via urethra a few drops at a time. This patient most likely sustained additional injury to what during his initial accident?

*Pelvic nerves* Micturition - initiated when increasing volume of urine stimulates stretch receptor in detrusor muscle in bladder wall - Afferent (GVA) impulses arise from stretch receptors in bladder wall & enter spinal cord (S2-S4) via pelvic splanchnic nerves - Parasympathetic fibers in pelvic splanchnic nerve induce contraction of detrusor muscle & relaxation of internal sphincter = urge to void

65 yo Caucasian male admitted following acute ST-segment elevation MI experiences chest pain on day four of his hospitalization. He describes the pain as sharp in quality, & adds that it increases with coughing & swallowing & radiates to his neck. BP is 130/80 mmHg, pulse is 90 beats per minute, temp is 38.3 (101 F) & respirations are 20 per minute. What is the most likely cause of this patient's chest pain?

*Pericardial inflammation overlying necrotic segment of myocardium* - sharp & pleuritic pain = pericardial involvement - exacerbation when swallowing = posterior pericardium - radiation to back = inferior pericardium = adjacent to phrenic nerve afferents supplying diaphragm - low-grade fever = inflammatory process Fibrinous or serofibrinous early-onset pericarditis = 10-20% of patients between 2-4 days after transmural MI - pericarditis = rxn to transmural necrosis - inflammation usually localized to region of pericardium overlying necrotic myocardial segment - generally short-lived & disappears with 1-3 days of aspirin therapy

A midline episiotomy is performed to expedite delivery. A vertical, midline incision is made at the posterior vaginal opening through vaginal & submucosal mucosa. What structures is most likely involved in this incision?

*Perineal body* = essential to integrity of pelvic floor - tendinous center point of perineum separates urogenital & anal triangles Structures anchored to perineal body = bulbospongiosus muscle = external anal sphincter muscle = superficial & deep transverse perineal muscles = fibers from external urethral sphincter, levator ani, muscular coat of rectum Midline episiotomy = vertical incision from posterior vaginal opening to perineal body - improperly done = pelvic organ prolapse or dyspareunia

21 yo man involved in motorcycle accident, resulting in destruction of groove in lower surface of cuboid bone. What muscle tendons in most likely damaged?

*Peroneus longus* - groove in lower surface of cuboid bone is occupied by tendon of peroneus longus muscle

Motorcyclist falls from bike in accident & gets deep gash that severs the superficial peroneal nerve near its origin. What muscle is paralyzed?

*Peroneus longus* & brevis

Non-pathogenic strains of Corynebacterium diphtheriae can acquire pathogenicity & thus ability to cause severe pseudomembranous pharyngitis through what mechanism?

*Phage conversion permitting exotoxin production* Diphtheria - acute toxin-mediated disease - not all strains of C diphtheriae express disease-causing exotoxin - acquires virulence via bacteriophage-mediated "infection" with Tox gene --> codes for diphtheria AB exotoxin Bacteriophage = Corynephage beta - phage Tox gene incorporates into bacterial chromosome as prophage --> codes for toxin production by C diphtheria = lysogenization

3 yo boy who recently immigrated to US is brought to physician by his parents because he has not yet begun to walk or speak. Assessment of his dev'tal milestones shows severe intellectual disability. He dies 6 months later form refractory seizures resulting in respiratory failure. Autopsy shows pallor of substantia nigra, locus ceruleus, & vagal nucleus dorsalis. The underlying condition responsible for this patient's death is most likely by a deficiency of what enzyme?

*Phenylalanine hydroxylase* - requires cofactor tetrahydrobiopterin (BH4) PKU = intellectual disability + history of seizures + abnormal pallor of catecholaminergic brain nuclei on autopsy - large concentrations of phenylalanine metabolites (phenyllactate & phenylacetate) = brain damage seen in PKU - hypopigementation via inhibitor effect of excess phenylalanine on melanin synthesis

Emergent coronary angiography performed, which demonstrates significant atherosclerotic involvement of LAD & circumflex arteries. What provides major proliferative stimuli for cellular components of atheroslerotic plaques?

*Platelets* - also release TGF-beta = chemotactic SMCs & induces interstitial collagen production Atherosclerotic plaques - begins with endothelial cell injury --> increased endothelial permeability, enhanced leukocyte adhesion, altered gene expression Endothelial dysfunction --> platelet adhesion, aggregation, release of growth factors & cytokines PDGF - released by adherent platelets, dysfunctional endothelial cells, infiltrating macrophages --> promotes migration of SMCs from media into intima & increases SMC proliferation

7-year-old boy who emigrated with his fam from Africa 4 days ago is brought to physician by his mother because of a 2-day history of headache and recurrent fever accompanied by back pain. The mother reports that a child in the village where they used to live had a similar condition 10 days ago. The patient's temp is 39 C (102.2 F). Physical exam shows weakness of the left lower extremity; the knee reflex is weaker on the left. Neurologic exam shows fasciculations of the lower extremity. What is the most likely diagnosis?

*Poliomyelitis* - case report = unimmunized kid from another country

30 yo woman comes to ED with acute-onset shortness of breath. Analysis of patient's expiratory gases reveals the following: Tracheal pO2 = 150 mmHg Alveolar pO2 = 145 mmHg Alveolar pCO2 = 5 mmHg What best explains the results of this patient's pulmonary gas analysis?

*Poor ALVEOLAR perfusion* Normal conditions - pO2 of inspired air = 160 mmHg --> decreases to 150 mmHg in trachea via partial pressure of water vapor - patient's tracheal pO2 is normal = she is breathing room air without any supplemental O2 - normal alveolar pO2 = 104 mmHg This patient... - failure of alveolar gas to reach normal equilibrium point = poor alveolar perfusion

67 yo man comes to office due to severe fatigue for past several months. Patient cannot eat as much as he used to and has lost nearly 10 kg (22 lb) in past 6 months. Physical exam shows mucosal pallor, hepatomegaly, & massive splenomegaly. Further evaluation reveals gain-of-function mutation of non-receptor tyrosine kinase protein in hematopoietic cells, leading to persistent activation of signal transducers & activators of transcription (STAT) proteins. This patient is most likely suffering from what disorder?

*Primary myelofibrosis* - hepatomegaly & splenomegaly via loss of bone marrow hematopoiesis compensated for by extramedullary hematopoiesis - peripheral smea = teardrop-shaped RBCs (dacrocytes) & nucleated RBCs = constitutive tyrosine phosphorylation activity --> cytokine-independent activation of signal transducers & activators of STAT pathway - atypical megakaryocytic hyperplasia --> stimulates fibroblast proliferation = progressive replacement of marrow space by extensive collagen deposition Early stages... - marrow hypercellularity with minimal fibrosis Progression - panctyopenia Ruxolitinib = JAK2 inhibitor = treatment of primary myelofibrosis Chronic myeloproliferative disorders = JAK2 mutation = polycythemia vera, essential thrombocytosis, primary myelofibrosis

23 yo man comes to ED with sudden onset of heart palpitations that started while he was at his desk at work. Patient has no known medical problems & does not use tobacco or illicit drugs. He drinks alcohol occasionally on the weekends. Initial BP is 110/70 mmHg & pulse is 160/min & regular. Gentle neck massage just below the angle of the right mandible provides immediate improvement of his condition? His BP is now 120/80 mmHg & pulse is 75/min. What mechanism is responsible for improvement of this patient's condition?

*Prolonged atrioventricular node refractory period* Paroxsymal supraventricular tachycardia (PSVT) = suddent onset of palpitations & rapid tachycardia = via reentrant impulse traveling circularly between slowly & rapidly conducting segments of AV node Vagal maneuvers = acutely terminates PSVT Carotid sinus massage = increased afferent firing from carotid sinus --> increases vagal parasympathetic tone - slows conduction through AV node --> prolongs AV node refractory period = helps terminate reentrant tachycardia

400 women aged 20-35 coming for routine check-up are asked about their smoking status. 40% of women are smokers. Over next ten years, 25 smokers & 24 non-smokers developed breast cancer. What best describes the study design?

*Prospective cohort study* - initially group of subjects selected (cohort) & their exposure status is determined (smoker/non-smoker) --> cohort then followed for certain period of time & observed for dev't of outcome (breast cancer)

Recognize *Urea, Bicarbonate* on tubular fluid/plasma ultrafiltrate in graph

- bicarb in proximal tubule = actively reabsorbed in proximal tubule via activity of carbonic anhydrase within proximal tubular cells = decreases as fluid runs along proximal tubule

35 yo man with HIV infection comes to physician for routine exam. He has been receiving highly active antiretroviral therapy for 2 years. Physical exam shows thin extremities, wide abdominal girth, and a buffalo hump on upper back. Lab studies show CD4+ T lymphocyte count = 43/mm^3 (N>500) Plasma HIV viral load = 1190 copies/mL Serum: Glucose = 110 mg/dL Total cholesterol = 225 mg/dL Triglycerides = 260 mg/dL Results of glucose tolerance test are abnormal. Drug from what classes is most likely cause of these lab findings?

*Protease inhibitors* Fat redistribution drugs - protease inhibitors, glucocorticoids Protease inhibitors - hyperglycemia - GI intolerance (nausea, diarrhea) - lipodystrophy (Cushing-like syndrome) subcutaneous lipoatrophy - nephropathy - hematuria - thrombocytopenia (indinavir)

Warfarin-induced skin necrosis caused by deficiency of

*Protein C* or S - innate anticoagulants that are vitamin K dependent - transient hypercoagulable state = microvasculature occlusion & hemorrhagic skin necrosis - treatment = discontinue warfarin and administer fresh frozen plasma or protein C concentrate

What does hemoglobin release as point goes up oxygen-hemoglobin dissociation curve?

*Protons* Transition up... - loading of O2 onto partially deoxygenated hemoglobin - as pO2 increases, O2 binds to 1 of 4 heme moieties on hemoglobin molecule = oxygen-binding affinity of other hemoglobin subunits increases = steepening of curve - additional O2 molecules bind as oxygen partial pressure increases Haldane effect = in lungs, binding of oxygen to hemoglobin drives release of H+ & CO2 from hemoglobin - Bohr effect = peripheral tissues = high concentrates of CO2 & H+ facilitate oxygen unloading from hemoglobin

12 yo Caucasian male found to have wide, fixed splitting of second heart sound (S2) on routine physical exam. He denies any symptoms. If present, the congenital heart disease in this patient may require surgical repair to prevent irreversible changes in the:

*Pulmonary vessels* ASD - creates left-to-right shunt because of high pressure in left atrium = increased blood flow through pulmonary artery - muscular pulmonary arteries may develop laminated medial hypertrophy so severe --> increases pulmonary vascular resistance above total systemic vascular resistance = reversal of left-to-right intracardiac shunt to right-to-left = late-onset cyanosis, clubbing, polycythemia = Eisenmenger syndrome - over time: pulmonary vascucular sclerosis becomes irreversible

6-week-old boy has 2-week history of projectile vomiting after feeding. Several changes in formula do not change his symptoms. Vomitus is free of bile. He is dehydrated, & stools are decreased. Serum electrolyte and pH findings show metabolic alkalosis. What is the most likely diagnosis?

*Pyloric stenosis* vomiting --> losing stomach acid (HCl) --> metabolic alkalosis & hypchloremia, & hypokalemia because of H/K exchange - H will go out, & K inside cells as body tries correcting alkalosis states

Recognize cryptococcus neoformans, which is stained with *mucicarmine stain*

- capule appears red on mucicarmine stain & as clear unstained zone with Indian ink - only pathogenic fungus with polysaccharide capsule

14 yo girl comes to physician with dark urine & facial puffiness. About 4 weeks before presentation, she had pustular skin lesions that broke down over a few days to form thick scabs in the lower extremities. Microscopic exam of urine sediment shows RBC casts. The organism responsible for this patient's symptoms would most likely demonstrate what?

*Pyrrolidonyl arylamidase positivity* Impetigo = skin infection caused by S aureus & less commonly by Streptococcus pyogenes / Group A Strep / GAS Post-streptococcal glomerulonephritis S pyogenes = catalase-negative = beta-hemolytic = gram-positive = cocci in chains = *susceptible to bacitracin* BUT not sensitive, so it was replaced by *pyrrolidonyl arylamidase (PYR) test* = PYR positive!

45 yo man comes to urgent care clinic because of fever, severe headache, myalgia, & pleuritic chest pain. He has had these symptoms for several days. Physical exam shows fever & mild tachycardia. Lung auscultation reveals mild crackles. Radiographic exam is consistent with segmental pulmonary infiltrates. Patient fails to respond to empiric antibacterial therapy. Microscopic exam of lung tissue obtained from this patient shows spherules packed with endospores. This patient's history is most likely to reveal what?

*Recent travel to Arizona* Coccidioides immitis - dimorphic fungus - mold form = hyphase = 25-30 C - endospore form = spherules containing endospores = characteristic!!! at body temp (37-40 C) - endemic to southwestern US - have likely liver in or have recently traveled to endemic area - immunocompetent = lung disease = asymptomatic or flu-like symptoms accompanied by erythema nodosum - spores are inhaled & turn into spherules in lungs

New portable cholesterol-measuring device being developed for use in medically underserved communities. During clinical trials of early prototype, a patient's cholesterol level is found to be 200 mg/dL on three separate measurements of same blood sample. Using gold standard measurement method, sample sample is found to have cholesterol level of 260 mg/dL. New cholesterol-measuring device is best described as what?

*Reliable but not accurate* Reliability = precision = measure of statistical variation = reproducible = similar or very close results on repeat measurements Validity = accuracy = test's ability to measure what it is supposed to measure

45 yo man with history of end-stage renal disease undergoes allograft renal transplant. Donor kidney & proximal ureter are transplanted in right iliac fossa, with implantation of ureter into patient's bladder. Six days following surgery, donor kidney appears to be functioning well, but patient develops fever & right lower quadrant abdominal pain. Imaging studies reveal large pelvis fluid collection. Exploratory laparotomy performed & discovers urinary leakage, with significant ischemia & necrosis of transplanted ureter immediately adjacent to site of implantation into bladder. Proximal portion of ureter appears normal. What arteries normally supplies blood to healthy segment of this patient's ureter?

*Renal artery* Blood supply to proximal ureter via branches of renal artery Distal ureter blood supply via superior vesical artery

5 yo boy brought to physician because of pain in the right eye at night for the past week. There is no family history of neoplasms. Exam shows strabismus and tenderness in the eye. The left eye is normal. Exam of the retina shows presence of a mass. The physician explains to the parents that the boy is unlikely to develop any other neoplasms. The first mutation leading to the neoplasm most likely occurred in what?

*Retinal cells* - if congenital, then yes, he had both Rb gene turned off then he will have more cancer BUT boy doesn't have congenital Rb because no one in fam has Rb - this is random, acquired mutation = only limited to retinal cells, not germ cells

External stimulus applied to cell increases activity of several enzymes, including dihydrofolate reductase & DNA polymerase. What immediately precedes observed effect?

*Retinoblastoma protein phosphorylation* Rb = regulator of G1-->S - active = hypophosphorylated - inactive = hyperphosphorylated - resting cells in G0 phase contain active (hypophosphorylated) Rb protein Cell stimulated by growth factor --> activation of cyclin D, cyclin E, & corresponding cyclin kinases (CDK 4 & 6) --> Rb protein hyperphosphorylated = inactive Hyperphosphorylated Rb --> releases E2F transcription factor --> cell progresses through G1 --> S checkpoint

During experiment, researcher blocks production of microtubule-associated (MAP-1C) ATPase (dynein) in neuronal cell body. This is most likely to cause reduction of what neuronal process?

*Retrograde axonal transport*

48 yo man admitted to hospital for treatment of idiopathic pulmonary HT. This patient has experienced progressive dyspnea over past 6 months. Cardiac cath shows decrease in cardiac function. The most likely cause of the decreased cardiac function is an increase in what?

*Right ventricular afterload*

Studies conducted following influenza epidemic that affected inhabitants of several countries determine that the cause is an antigenetically novel virus strain carrying the animal-strain hemagglutinin & neuraminidase surface molecules. Further analysis reveals reassortment of genetic materials occurred during coinfection with human influenza virus & swine influenza virus, leading to development of some progeny that contain genetic materials from both viruses. What viruses can undergo a similar process?

*Rotavirus* Genetic shift in influenza A = reassortment of genomic segments of human strain with genomic segments of animal strain = typically when both strains coinfect birds (avian) or pigs (swine) = new strain can cause new influenza epidemic or pandemic if dramatically altered viral surface glycoproteins (ex. hemagglutinin) Segmented genomes = key - rotavirus = similar mechanism

55 yo Caucasian male brought to ER with sudden onset severe substernal chest pain, as well as sweating & mild dyspnea. Pain does not respond to aspirin or sublingual nitroglycerin. His past med history is significant for HT, diabetes & hyperlipidemia. ECG demonstrates ST-segment elevations in leads I, aVL, & V1-V3 with deep Q-wave dev't over next several hours. Cardiac cath in this patient would most likely show what?

*Ruptured atherosclerotic plaque with fully obstructive thrombus* Acute transmural MI - severe chest pain not relieved by rest or nitroglycerin, diaphoresis, dyspnea, nausea, lightheadedness, palpitations - peaked T waves = first ECG sign = reflecting localized hyperkalemia - ST-segment elevation follows within minutes to hours - hours to days = Q-waves

46 yo missionary who just returned from trip to Latin America comes to clinic with fever, headache, abdominal pain, & a 1-week history of watery diarrhea that has recently become bloody. His temperature is 38.9 C (102 F). Physical exam shows hepatosplenomegaly & several faint, erythematous maculopapular lesions on chest & abdomen. Blood cultures are pending. What is the most likely cause of this patient's symptoms?

*Salmonella TYPHI* / Paratyphi Typhoid fever - life-threatening - common in developing countries - recent travel history to endemic area - fecal-oral route - ingestion of contaminated food or water - fever with relative bradycardia followed by watery diarrhea OR constipation, abdominal pain, & salmon-colored rose spots on chest/abdomen - widespread dissemination across reticuloendothelial system (liver, spleen, bone marrow) --> hepatosplenomegaly - ulceration of Peyer's patches = GI bleeding - at risk for becoming chronic carriers, particularly those with cholelithiasis or other biliary tract abnormalities that allow S Typhi to persist in bile

Patient has weakness when flexing both her thigh & leg. What muscles is most likely injured?

*Sartorius* - can flex & rotate laterally - can flex & rotate leg medially

28 yo basketball player falls while rebounding & is unable to run & jump. On physical exam, he has pain & weakness when extending his thigh & flexing his leg. What muscle involved in both movements is most likely injured?

*Semitendinous* - extends thigh & flexes leg

7-month-old boy brought to physician by his parents due to irritability & white patches in his mouth. His past medical history is significant for 3 episodes of otitis media & 2 episodes of bronchiolitits that have required hospitalization. He also has a history of chronic loose stools. The child is small his age and ill-appearing. Head & neck exam shows white patches consistent with oral candidiasis but is otherwise normal. Auscultation of lungs shows expiratory wheezing. Cardiac exam is within normal limits. Lab results are as follows: Sodium = 140 mEq/L Potassium = 3.8 mEq/L Chloride = 98 mEq/L Bicarbonate = 24 mEq/L Calcium = 9.6 mg/dL Serum protein electrophoresis shows very low gamma globulin level. Chest x-ray reveals absent thymic shadow. What is the most likely diagnosis?

*Severe combined immunodeficiency* (SCID) = presents in infancy = severe viral & bacterial infections as maternal immunity wanes = mucocutaneous candidiasis, persistent diarrhea, failure to thrive = very low or absent CD3+ T cells & hypogammaglobulinemia = thymic hypoplasia or aplasia

53 yo man comes to office due to 7-8 months of shortness of breath. He states that he feels most short of breath when chopping wood for fireplace. Several of his coworkers have experienced similar symptoms. He has history of HT & type 2 DM. Pulmonary exam reveals diffuse fine crackles. Chest x-ray reveals nodular densities in both lungs that are most prominent at apical regions. Calcification of hilar lymph nodes is also seen. Bronchoscopy with transbronchial biopsy of calcified node is performed, & polarized microscopy shows birefringent particles surrounded by dense collagen fibers. This patient most likely has history of exposure to what substances?

*Silica* = middle-aged adult + dyspnea on exertion + nodular densities on x-ray + calcified hilar lymph nodes + birefringent particles on biopsy = presents 10-20 years after initial exposure = calcification of rim of hilar nodes = eggshell calcification = birefringent silica particles surrounded by fibrous tissue on histology = upper lobes!!!

Coronary angiography of 69-year-old Caucasian female with chronic atypical chest pain shows extensive atherosclerosis & near-total occlusion of left LAD artery. The absence of myocardial necrosis & scarring despite vessel occlusion in this patient can best be explained by what features of occluding plaque?

*Slow growth rate* - allows for more formation of collateral that could prevent myocardial necrosis Major determinant of whether or not coronary artery plaque will cause ischemic myocardial injury = rate at which it occludes involved artery

Referring to the electrical activity of cardiac pacemaker cells in the slow-response tissues such as SA and AV nodes in the patient's heart, what effects would verapamil administration most likely have on these cells?

*Slowed diastolic depolarization* Class IV antiarrhythmics = verapamil, diltiazem = prevent recurrent nodal tachycarrhythmias such as PSVT = block L-type calcium channels in cardiac slow-response tissues = slow phase 4 depolarization

Patient undergoes allograft lung transplant. His postoperative course is complicated by mild acute rejection, which is successfully treated with immunosuppressant therapy. What is most likely to be primarily damaged by chronic rejection of this patient's allograft?

*Small airways* = bronchiolitis obliterans = inflammation & fibrosis of bronchiolar walls = narrowing & obstruction of affected bronchioli Chronic rejection - months or years after transplantation - major cause of mortality in lung transplant

48 yo woman comes to office due to intermittent ear discharge over last 2 years. She has also noticed decreased hearing in right ear recently. Past medical history is significant for obesity, hyperlipidemia, seasonal allergies, & diet-controlled diabetes mellitus. Otoscopy shows small perforation in right tympanic membrane & a pearly mass behind membrane. Conduction hearing loss is noted in right ear. Remainder of ear, nose, & throat exam is normal. What is the most likely cause of this patient's aural mass?

*Squamous cell debris* Cholesteatomas = collection of squamous debris = round, pearly mass behind tympanic membrane in middle ear - most commonly cause painless otorrhea - can produce lytic enzymes - often discovered when erode through auditory ossicles = conductive hearing loss - if mass grows sufficienctly large, it can erode into vestibular apparatus or facial nerve = vertigo of facial palsies - can occur congenitally or may develop in adults as either acquired primary lesion or secondary to infection, trauma, or surgery of middle ear Primary cholesteatomas = via chronic negative pressure in middle earl --> retraction pockets in tympanic membrane that becomes cystic - squamous cell debris accumulates --> cholesteatoma formed Secondary cholesteatoma - squamous epithelium migrates to or is implanted in middle ear (skin in wrong place)

74 yo previously healthy Caucasian male comes to his physician's office complaining of abrupt onset fever, headache, myalgias, malaise, cough & throat pain. His two graddaughter's missed several days of school because of similar symptoms. Exam demonstrates mild hyperemia of throat withour any exudate, & the patient is sent home on conservative management. Five days later, he is admitted to hospital with progressive dyspnea, chest pain, & productive cough. What pathogens is most likely to be isolated from patient's sputum?

*Staphylococcus aureus* or S pneumo, H influenza Influenza - outbreaks of influenza A affect 50-70% fo school-aged children --> spread virus to fam members - subset of patients go on to develop secondary bacterial pneumonia = recurrent fever, dyspnea, productive cough In order, pathogens most often responsible for secondary bacterial pneumonia: *Strap pneumonia, Staph aureus, H influenza*

What would most likely increase the intensity of a murmur in a patient with hypertrophic cardiomyopathy?

*Sudden standing* Valsalva (straining phase) Nitroglycerin - decreases preload HCM - dynamic left ventricular outflow tract (LVOT) obstruction = harsh crescendo-decerescendo systolic ejection-type murmur heard along lower left sternal border & apex

42 yo man comes to office due to numbness & tingling in both legs & difficulty walking for past several months. He has also noticed that he tires more easily with physical activity. His temp is 36.8 C (98 F), BP is 122/86 mmHg, pulse is 76/min, & respirations are 14/min. Physical exam shows conjunctival pallor & loss of vibration & position sensation in bilateral lower extremities with associated gait ataxia. The remainder of exam is within normal limits. What findings is most likely to be present upon further questioning of this patient?

*Strict vegan diet for past 6 years* B12 / cobalamin - animal products - deficiency after complete absence of intake for 4-5 years Subacute combined degeneration of spinal cord

Patient has aortic stenosis. Patient comes to ED with palpitations & increased shortness of breath. His BP is 90/60 mmHg & his heart rate is 130/min with an irregularly irregular rhythm. ECG shows new-onset atrial fibrillation without significant ST-segment or T-wave changes. Chest x-ray shows bilateral pulmonary edema. What hemodynamic changes is most likely associated with this patient's current presentation?

*Sudden decrease in left ventricular preload* Atrial fibrillation - sudden-onset heart failure - 10% of patients with severe aortic stenosis - without atrial contraction, LV preload can decrease to point of producing severe hypotension - loss of atrial kick --> increase mean pulmonary venous pressure via buildup of blood in left atrium & pulmonary veins --> acute pulmonary edema

Patient involved in motorcycle wreck that results in avulsion of skin over anterolateral leg & ankle. What nerve is most likely destroyed with this type of injury?

*Superficial peroneal nerve* - emerges between peroneus longus & peroneus brevis muscles - descends superficial to extensor retinaculum of ankle on anterolateral side of leg & ankle - innervates skin of lower leg & foot

30-year-old woman undergoes cervical biopsy because of Pap smear showing high-grade intraepithelial lesion. What locations of the neoplastic cells in the tissue sample is most consistent with in situ cervical carcinoma?

*Superficial to the basement membrane* Dysplasia and carcinoma in situ - disordered epithelial growth - begins at basal layer of squamocolumnar junction (transformation zone) and extends outward Carcinoma in situ = *severe dysplasia with high likelihood of progression to invasive carcinoma BUT intact for the moment*

Biologists investigating morphologic changes associated with reversible cellular injury perform a procedure on anesthetized mice to assess effects of transient hepatic ischemia. During experiment, they clamp hepatic artery & obtain liver biopsy samples at varying intervals. Samples are then examined by EM. Cells that are exposed to longer ischemic periods are found to have reduced numbers of ribosomes attached to the ER. This structural change is most likely to impair what cellular functions?

*Synthesis of cell membrane proteins* Ribosomes - synthesize proteins = 2 subunits - small ribosomal 40S --> binds mRNA & tRNA - larger 60S = contains peptidyl transferase --> catalyzes peptide bond formation between AAs - begin protein translation in cytoplasm but some translocate to RER during protein synthesis depending on protein's target destination

8-year-old boy with one week history of fever & throat pain is brought to ED with severe dyspnea, tachypnea, & inspiratory stridor. He has also experienced worsening dysphagia with solid foods over last two weeks. Lab evaluation reveals many immature hematopoietic cells (blasts) in peripheral blood smear. The neoplastic cells causing patient's condition normally gives rise to what?

*T lymphocytes* - blast cells = leukemia! - most common pediatric malignancy = ALL ALL - neoplastic cells arise form lymphoblastic precursors that are of either pre-B or pre-T lineage T-cell ALL = more likely to present with large anterior mediastinal mass --> can compress great vessels = SVC syndrome - mediastinal mass can compress esophagus = dysphagia; trachea = dyspnea or stridor Both lineages = TdT = Ag of lymphocyte precursors pre-T lymphoblasts = CD2+, CD3+, CD4+, CD5+, CD7+, CD8+

56 yo Caucasian female with one-week history of dysuria & flank pain develops chills, high fever, & confusion. Her BP is 80/40 mmHg & her heart rate is 120/min. Her extremities are warm and her breath is rapid & shallow. What substances is most likely responsible for the patient's current symptoms?

*TNF-alpha* = most important mediator of sepsis = acute phase cytokine produced by activated macrophages Septic shock - infection + hypotension + tachycardia + tachypnea + elevated or decreased body temp - early = increased cardiac output, peripheral vasodilation, warm extremities - progression = stroke volume decreases, cardiac output decreases, distal hypoperfusion becomes evident

3 tests evaluate children with diarrhea for rotavirus. Sensitivity and specificity are summarized. If only treat children actually have disease because of toxicity of treatment, which tests should be run? Test 1 Sensitivity 70 and Specificity 100 Test 2 Sensitivity 90 and Specifiticity 95 Test 3 Sensitivity 95 and Specificity 70

*Test 3, followed by Test 1 if positive* Test 3 = 95% of people with disease, but since you are going to have a lot of false positives, you use test 1, which is always negative in false positives*

While playing football, a 19 yo college student receives a twisting injury to his knee when being tackled from the lateral side. What conditions most likely has occurred?

*Tear of medial meniscus* Unhappy triad = tear of medial meniscus, rupture of tibial collateral ligament, rupture of anterior cruciate ligament - may occur when cleated shoe, as worn by football players, is planted firmly in turf and knee is struck from lateral side

Recognize *aminoaciduria* causing Cystinuria

- recurrent nephrolithiasis in young patient - hexagonal-shaped crystals - AR - defective sodium-independent diabasic AA transporter on apical membrane of intestinal & proximal renal tubular epithelial cells - prevents dibasic AAs (cysteine, ornithine, lysine, & arginine) from being reabsorbed in proximal renal tubules = urine supersaturation = cystine stones - sodium-cyanide-nitroprusside test = qualitative screening test --> positive test = red-purple discoloration - treatment = increased hydration & urinary alkalinization (acetazolamide)

35 yo woman comes to physician complaining of weakness, fatigue, & pallor. She denies menses or melena. Physical exam is unremarkable except for conjunctival pallor. Lab results are as follows: Complete blood count: Hemoglobin = 7.2 g/dL Erythrocyte count = 1.8 million/uL MCV = 90 fL Reticulocytes = 0.1% Platelets = 280,000/uL Leukocyte count = 6,700 cells/uL Iron studies & serum B12 & folic acid levels are within normal limits. Bone marrow biopsy shows absence of erythroid precursors but preserved myeloid & megakaryocytic elements. Further workup would most likely show what?

*Thymic tumor* / Thymoma - removal can cure it sometimes Pure red cell aplasia (PRCA) - severe hypoplasia & marrow erythroid elements in setting of normal granulopoiesis & thrombopoiesis = inhibition of erythropoietic precursors & progenitors by IgG autoAbs or cytotoxic T lymphocytes Associated with... - thymomas - lymphocytic leukemias - Parvovirus B19 = can be detected with anti-B19 IgM Abs in serum

Construction worker is hit on leg with concrete block & is subsequently unable to plantar flex & invert his foot. What muscles is damaged?

*Tibilias posterior* - plantar flexes & inverts foot

Erythroblasts isolated from bone marrow biopsy sample of patient with neonatal jaundice are incubated in medium containing glucose. The cells are unable to generate NADPH from glucose metabolism but are able to convert glucose-6-phosphate to ribose-5-phosphate, which is required for nucleic acid synthesis. What enzymes is essential for the latter conversion?

*Transketolase* Pentose phosphate pathway = HMP shunt - generates NADPH for reductive reactions - generates ribose-5-phosphate = precursor for nucleotide synthesis - ribose-5-phosphate in excess = transketolase & transaldolase can produce glycolytic intermediates glyceraldehyde-3-phosphate & fructose-6-phosphate for ATP generation - ribose-5-phosphate demand exceeds production capability of oxidative pathway = nonoxidative pathway functions in reverse --> transketolase & transaldolase enzymes catalyze conversion of fructose-6-phosphate & glyceraldehyde-3-phosphate to ribose-5-phosphate

Plasma homocysteine levels measured in patients with acute coronary syndrome who are treated at large community hospital. Mean plasma homocysteine level in this group is determined to be 11.1 umol/L with standard deviation of 1.2 umol/L. In a separate group of patients hospitalized on general ward in same hospital, mean plasma level is 9.5 umol/L & standard deviation is 1.3 umol/L. What statistical methods should be used to compare mean homocysteine levels of these 2 groups of patients?

*Two-sample t-test* = determines if means of 2 populations are equal - basical numerical requirements = 2 mean values, sample variances (standard deviations), sample sizes - t statistic calculated, from which p value can be determined - p < 0.05 = null hypothesis (which assumes there is no difference between 2 groups) is rejected & 2 means are assumed to be statistically different

22 yo man comes to office due to recurrent blistering on back of his hands & forearms for past several years. Patient usually develops small itchy spots but lately has had large blisters that heal with hyperpigmentation after rupturing. He has used over-the-counter topical hydrocortisone & emollients, but symptoms have not improved. Patient works as night security guard and has had no exposure to chemicals or animals. He drinks 2-3 cans of beer daily. Physical exam shows vesicles and erosions on dorsum of both hands. What enzymes is most likely deficient in this patient?

*Uroporphyrinogen decarboxylase* Porphyria cutanea tarda (PCT) = most common disorder of porphyrin (heme) synthesis = UROD deficiency = inherited or more commonly acquired in presence of iron & of susceptibility factors (alcohol, smoking, halogenated hydrocarbons, hepatitis C, HIV) - photosensitivity = vesicles & blisters on sun-exposed areas Enzyme deficiencies in early step = abdominal pain, neuro symptoms Enzyme deficiencies in late steps = photosensitivity via accumulation of porphyrinogen (reacts with O2 on excitation with UV light)

60 yo woman, gravida 1, para 1, comes to office with abdominal distention and decreased appetite. She also has lost 10 pounds (4.5 kg) unintentionally over past few months. She takes no meds & has received all recommended vaccinations except for human papilloma virus. Patient's mother has BRCA-positive ovarian cancer & died at age of 55. BMI is 30 kg/m^2. Imaging studies reveal right-sided ovarian mass & accumulation of free peritoneal fluid. Her blood work shows marked elevation of CA-125. What most likely would have reduced the risk of this patient's condition?

*Use of oral contraceptives* Epithelial ovarian cancer (EOC): Protective factors - oral contraceptives, multiparity, breastfeeding = less repair at ovarian surface via reduced lifetime ovulation frequency - pathogenesis linked to frequency of trauma and repair at ovarian surface Risk factors - BRCA mutation, nulliparity, infertility

1 week old boy brought to office for first primary care visit. Boy was born to 30 yo woman who took prenatal vitamins throughout pregnancy. She was diagnosed with gestational diabetes mellitus at 28 weeks gestation, which was treated with dietary modification & exercise. Nursery course was uncomplicated, & boy was discharged at around 30 hours of life following observation of appropriate breastfeeding, voiding, and stooling. His weight, length, & head circumferece are at 50th percentile. Physical exam shows grade II/VI harsh, holosytolic murmur best heard at left mid to lower sternal border. Birth records show that no murmur was heard by 2 different health care providers in newborn nursery. What is the most likely diagnosis?

*Ventricular septal defect* = most common congenital heart lesion - echocardiography should be performed small = loud, "blowing," holosystolic murmur at mid to lower left sternal border & no symptoms = usually not detectable at birth = becomes audible around age 4-10 days as pulmonary vascular resistance (PVR) continues to decline = left-to-right shunting moderate to large = heart failure, failure to thrive, diaphoresis with feeding = can result in chronic pulmonary HT & cyanosis (Eisenmenger syndrome) if not closed early in life

Small area of brain of 54 yo male shows neuronal shrinkage & intense cytoplasmic eosinophilia. If patient survived, eventually the are would most likely demonstrate:

*glial hyperplasia* Irreversible neuronal damage in area of brain --> gliosis = glial hyperplasia Astrocytes = tissue repair = proliferate at site of injury = astrocytosis/gliosis --> later, after neuronal death, astrocyte processes = firm meshwork = gliotic scar

52 yo woman with coronary artery disease is found to have heart with right-dominant coronary circulation. After angioplasty of circumflex artery, what structures by it would receive increased blood flow?

*left ventricle* Right-dominant circulation = 85% - PDA arises from RCA LCX - supplies posterolateral left ventricle and anterolateral papillary muscle - *supplies left ventricle in right-dominant systems* - if coronary anatomy is left-dominant, LCX still supplies 40-50% of left ventricle

Most characteristic biochemical feature of Huntington disease

*loss of GABA-containing neurons* = decreased GABA in brain

During an experiment, an isolated skeletal muscle is placed in a bath with a high concentration of glucose for 2 hours. The muscle is then contracted with electrical stimulation. An intracellular decrease in what most likely indicates the onset of fatigue?

*pH* - says decrease!!! - be careful with wording

In a traumatic intracranial hemorrhage / transtentorial (uncal) herniation), damage of what structure explains mid-positioning & fixed pupils & *rigid extension of upper & lower extremities*?

*pons* - brainstem compression Damage to brainstem *at or below level of red nucleus (midbrain tegmentum, pons)* = decerebrate (extensor) posturing via loss of of descending excitation to upper limb flexors (rubrospinal tract) & extensor predominance (via unopposed vestibulospinal tract output) - damage to neural structures above red nucleus (cerebral hemispheres, internal capsule) would result in decorticate (flexor) posturing via loss of descending inhibition of red nucleus & hyperactivity of upper limb flexors

Lambert-Eaton associated with Abs against

*presynaptic calcium channels* - associated with underlying malignancy

Varicose veins are most likely to be complicated by...

*skin ulcerations* Varicose veins = dilated, tortuous veins - superficial veins of leg - valvular incompetence Risk factors = chronically increased lower-extremity venous pressure (long periods of standing), age >50, obesity, multiple pregnancies) Common complications - painful thromboses, stasis dermatitis, skin ulcerations, poor wound healing, superficial infections

Thoracic surgeon going to collect portion of greater saphenous vein for coronary bypass surgery. He has observed that this vein runs

*superficial to fascia lata of thigh* Greater saphenous vein - ascends superficial to fascia lata - courses anterior to medial malleolus & posterior to medial condyles of tibia & femur - terminates in femoral vein by passing through saphenous opening

Adhesion of platelets to subendothelial surface requires interaction of platelet membrane glycoprotein with what?

*von Willebrand factor* Platelet plug formation (primary hemostasis): Adhesion - platelets bind vWF via GpIb receptor at site of injury only (specific) --> platelets undergo conformational change --> platelets release ADP and Ca2+ (necessary for coagulation cascade), TXA2 --> ADP helps platelets adhere to endothelium

Recognize *blastomyces dermatitidis*

- dimorphic fungus - round or oval yeasts with thick walls & broad-based budding - southeastern US - lungs = primary site - skin & bone = sites of dissemination

Recognize aortic regurgitation

- early diastolic murmur - most commonly caused by aortic dilation (right sternal border) or biscuspid valve in developed countries (left sternal border)

Recognize hydatid cyst caused by echinococcus granulosus, which can cause *anaphylaxis*

- endemic regions or US with sheeps & dogs - liver often affected = hepatomegaly or RUQ pain - echinococcal larvae implant within capillaries --> trigger inflammatory reaction involving monocytes & eosinophils - eggshell calcification = encapsulated & calcified cysts - outer wall = gelatinous sheets surrounded by thick fibrous capsule - imgaing (ultrasound, CT, MRI) & serology testing can be used for diagnosis - treatment = albendazole

Recognize spontaneous pneumothorax of left, which would cause *decreased breath sounds on left* Case: a 25 yo man comes to the ED 5 hrs after developing shortness of breath and chest pain during exercise. he has no cough or bloody mucus. he has asthma and major depressive disorder. current medications include flucasone inhaler and albuterol. his temp is 37.1 deg celsius, pulse is 110/min, resp rate is 30/min and BP is 90/60mmhg. pulse oximetry on room air shows an oxygen saturation of 93%. cardiac examination shows a normal s1 and s2 with no murmurs and no increase in jugular venous pressure. lab studies show bh 13g/dL hct 39% ABG on room air shows ph 7.46 pco2 26mmhg p02 60mmhg a chest xray is shown.

- flattened diaphragm - increased air on that side

Recognize different levels of spinal cord cross sections

- gracile & cuneat fasciculi present above T7, whereas only gracile fasciculus is present below this level

Recognize *malrotation* Case "A 24 year old man comes to the ED b/c of a 2 hour history of severe abdominal pain. HIs pulse is 110/min. Abdominal exam shows distension. An X-ray of the abdomen while the patient is sitting upright and an image from the upper GI series are shown. Based on the findings shown, this patient most likely has which of the following developmental anomalies?"

- looks like large part of abdomen is absent of bowel - malrotation of midgut loop around SMA possibly - air on left side = could be caused by volvulus

anaplastic tumors demonstrate what features?

- loss of cell polarity with complete disruption of normal tissue architecture --> coalesce into sheets or islands in disorganized, infiltrative fashion - variant in shape & size of cells (cellular pleomorphism) & nuclei (nuclear pleomorphism) - disproportionately large nuclei (high nucleu-to-cytoplasm ratio) that are often deep-staining (hyperchromati) with abundant, coarsely-clumped chroamtin & large nucleoli - numerous, abnormal mitotic figures - *giant, multinucleated tumor cells*

Recognize *rhizopus species*

- mucor, rhizopus, absidia = saprophytic fungi in env't = transmitted by spore inhalation --> cause mucormycosis Mucormycosis = strong association with diabetic ketoacidosis = affects paransal sinuses = facial & periorbital pain, headache, purulent nasal discharge = proliferate in walls of blood vesses = necrosis of corresponding tissue = black eschar (necrotic tissue) may be seen on palate or nasal turbinates = exist in mold form only = surgical debridement + amphotericin B

Recognize transepithelial transport of water

- no carrier protein needed

Recognize *X-linked recessive* inheritance pattern

- only males affected - male offspring of unaffected parents affected - no evidence of male-to-male transmission - asymptomatic carrier female in first generation - affected males always produce unaffected sons & carrier daughters - carrier females have 50% chance of producing affected son or carrier daughter

Recognize *parietal cells* Stem: "51 yo woman comes to physician bc of 6-month history of burning abdominal pain the occurs 1 to 2 hours after eating. She sweats profusely and has light-headedness when she stands. Her BP is 105/70 mmHg while standing. Physical exam shows epigastric tenderness. CT scan of abdomen shows 2 cm mass on proximal duodenum. Gastrin released by tumor cells stimulates what labeled cells in photomicrograph shown to release hydrogen ions?"

- parietal cells = large & round in shape & eosinophilic bc of mitochondria - upper regions = eosinophilic parietal or oxyntic cells - lower regions = chief or zymogenic cells

Recognize septic pulmonary embolism, caused by *tricuspid valve endocarditis* "33 yo man comes to hospital due to 3 days of shortness of breath, profound fatigue, & chills. Patient has history of IV drug abuse."

- wedge-shaped hemorrhagic lesion in periphery of lung - via pulmonary emboli - dual blood supply to lungs (pulmonary & bronchial arteries) = pulmonary emboli typically develop hemorrhagic infarction as opposed to ischemic infarction IV drug users = increased risk for bacterial endocarditis involving right-sided heart valves

Recognize *right mainstem bronchus obstruction* "65 yo man with long history of smoking comes to ED with shortness of breath & chronic mild cough. Symptoms progressed gradually over last week & today have become suddenly worse. Patient has HT that is controlled with hydrochlorothiazide. Pulse oximetry shows 86% on room air. Has decreased breath sounds over right chest."

- x-ray Collapses lung due to bronchial obstruction - decreased breath sounds, hemithorax opacification on right, deviation of trachea toward opacified side - complete collapse of lung after obstruction of mainstem bronchus (cnetral lung tumors in chronic smokers) - air trapped in lung gradually absorbed in blood --> loss of lung volume via alveolar collapse (atelectasis) = trachea deviates toward affected side - loss of radiolucent air + shifting of organs into hemithorax = *completely opacified hemithorax* on chest x-ray

Recognize *sarcoidosis*

- young adults: women - lungs mostly - bilateral hilar lymphadenopathy - non-caseating granulomas

Recurrent Stroke Rates per 1000 Person-Years Women: Standard Treatment = 0.12 New Antiplatelet Drug = 0.04 Men: Standard Treatment = 0.24 New Antiplatelet Drug = 0.08 Overall: Standard Treatment = 0.18 New Antiplatelet Drug = 0.06 Based on the results, what is the absolute risk reduction in women?

0.12 - 0.04 = 0.08 *8%*

What cephalosporins can be used in Pseudomonas?

3rd & 4th generation: 3rd gen = Ceftazidime 4th gen = *Cefepime* Pseudomonas - look for gram-negative rose in burn victims = oxidase-positive = non-lactose-fermenting

Inferior parathyroids derived from

3rd branchial pouch - and thymus

Recognize *coccidioides immitis*

= dimorphic fungus = desert areas of US & Mexico = lung disease in immunocompetent & disseminated disease in immunocompromised = exists in env't in form of mold *hyphase) = *thick-walled spherules packed with endospores* - some spherules may be rupturing, while others may be empty - cuture on Sabouraud agar & serology = important for diganosis

Recognize *intradermal nevi*

= older lesions = in which epidermal nests of nevus cells have been lost = dome-shaped = sometimes pedunculated

Cardiac AP conduction speed, slowest to fastest

AV node --> Purkinje system

Recognize *decompensated heart failure* "54 yo man. Worsening shortness of breath for last 3 days. Symptoms presented initially with exertion but now occur even at rest. Patient could not sleep last night because of suffocating cough that occurred each time he tried to lie down."

Acute decompensated heart failure - progressive dyspnea & orthopnea (cough when lying down) - chest x-ray = cephalization of pulmonary arrows, perihilar alveolar edema, blunting of costophrenic angles (pleural effusions) - via left ventricular systolic or diastolic dysfunction - increased atrial & ventricular filling pressures transmitted to pulmonary vasculature = fluid transudation into pulmonary interstitial & alveolar spaces (cardiogenic pulmonary edema)

Recognize general areas where *Atrioventricular groove* would be

Biventricular pacemaker: Preferred transvenous approach - passing left ventricular pacing lead from right atrium into coronary sinus, which resides in atrioventricular groove on posterior aspect of heart --> then advanced into one of lateral venous tributaries in order to optimize left ventricular pacing

30 yo woman with Marfan syndrome brought to ED 30 minutes after onset of tearing chest pain. Echocardiogram obtained 1 year ago showed aortic root to be 5.5 cm (N<4.0). She stopped taking her prescribed propranolol 1 year ago because of fatigue. Her pulse is 120/min, & BP is 80/40 mmHg. Physical exam shows JVD distention 6 cm above sternal angle that does not decrease with inspiration. The point of max impulse is not palpable, & the heart sounds cannot be distinguished. What sets of findings is most likely on cardiac catheterization of this patient? Cardiac index = Right atrial pressure = Pulmonary capillary wedge pressure = Pulmonary diastolic arterial pressure = Systemic vascular resistance =

Cardiac index = decreased = 1.8 - 2.5 = fancy word for CO Right atrial pressure = increased Pulmonary capillary wedge pressure = increased = LVEDV Pulmonary diastolic arterial pressure = increased Systemic vascular resistance = increased Aortic Dissection - Marfan + tearing chest pain (radiating to back) + aortic root dilation Cardiac tamponade - due to rupture into pericardiac sac = # 1 common location for rupture = compression of heart = massive blood in pericardiac sac --> increased pressure on right ventricle & right atrium --> beck's triad = hypotension (inability to fill), distended neck veins, distant heart sounds

Recognize *compound melanocytic nevus* Case: "28 yo previously healthy woman comes to office for evaluation of raised, pigmented skin lesion of leg. Has not itching or pain & cannot remember how long she has had the lesion. She has used tanning machines few times in the past but denies excessive sun exposure. She is particularly concerned about risk of malignancy as her father was recently diagnosed with skin cancer." "Biopsy of lesion reveals nests of uniform round cells at basal portion of epidermis that extend into underlying dermis. The cells contain inconspicuous nucleoli and show no mitotic activity. What is the most likely diagnosis?"

Compound nevi = aggregates of nevus cells extend into dermis = raised papules with uniform brown to tan pigmentation

Recognize epithelial ovarian cancer, which has a marker of *CA-125*

Epithelial Ovarian Cancer = Serous cystadenoacrinomas and Mucinous cystadenocarcinomas = most common subtype = *anaplasia of epithelial cells with invasion into ovarian stroma, multiple papillary formations with cellular atypia, occasional Psammoma bodies* CA-125 = protein expressed by epithelial cells lining Mullerian organs (ovary, fallopian tubes) & peritoneum Ovarian cancer = abdominal distention, constipation, abdominal/pelvic mass, ascites, decreased appetite due to compression by tumor or cancer invasion

Know how to calculate total peripheral resistance of circuit with parallel vessels...

Ex. Resistance in each of four vessels shown at bottom is 2 mmHg/mL/min (R1 = R2 = R3 = R4 = 2 mmHg/mL/min). What is the total peripheral resistance of the circuit shown? *0.5* 1/RT = 1/R1 + 1/R2 + 1/R3 ... 1/TPR = 1/2 + 1/2 + 1/2 + 1/2 = 4(1/2) = 2 TPR = 1/2 = 0.5 mmHg/mL/min Total body circulation can be best described as parallel circuit, whereas circulation in individual organ is best described by series

Recognize granulomatous formation, which can be *reaction to foreign body* Case: "17 yo man comes to physician because of painful subcutaneous nodule on his left forearm. Two weeks earlier, he suffered laceration to his forearm while playing soccer & had sutures placed. Biopsy of the lesion is taken and results are shown."

Foreign bodies / retained sutures - can elicit granulomatous response - aggregates of macrophages that assume epithelioid appearance - surrounded by rim of lymphocytes = chronic inflammation

Recognize *c-ANCA*, which is associated with *Crescentic glomerulonephritis*

Granulomatosis with polyangiitis (Wegener's) = necrotizing granulomatous vasculitis" "hemoptysis, HT, hematuria" = type 3 / pauci-immune = rapidly progressive/crescentic glomerulonephritis (RPGN) type 3 (pauci-immune) = signs of upper & lower respiratory tract inv't

middle aged man + massive splenomegaly + unsuccessful bone marrow aspiration + pancytopenia

Hairy cell leukemia = *lymphocytes with cytoplasmic projections*

Recognize *failed lateral fusion of paramesonephric ducts* on MRI

Incomplete lateral fusion of upper segments = bicornuate uterus = indentation in center of fundus Complete lack offusion = uterine didelphys (double uterus & cervix) Difficulty conceiving or recurrent pregnancy loss = screening with hysterosalpingogram (HSG) = contrast injection through cervix into uterus with concurrent pelvic x-ray This patient = 2 unfused uterine horne with central filling defect = bicorunate uterus or longitudinal uterine septum

Recognize acute tubular necrosis, which is *tubular re-epithelization*

Initiation phase = original ischemic or toxic insult = 36 hours = only slight decrease in urine output as renal tubular damage begins Maintenance phase = tubular damage fully established = oliguria, fluid overload, electrolyte abnormalities = 1-2 weeks = GFR stabilizes - light microscopy = tubular epithelial necrosis, casts Recovery phase = *re-epithelization of tubules* = GFR recovers quickly as tubules clear of casts & debris Most patients experience complete restoration of renal function

Probability of being free of disease if test result is negative

Negative predictive value (NPV) = correlates with low probability of having disease

500 workers w/bladder cancer and 200 w/o bladder cancer are selected for a study. Hx obtained of aniline dye exposure. Of the 500 w/bladder cancer, 250 have exposure to aniline dye. Of the 200 w/o bladder cancer, 50 have exposure. What's the odds ratio for exposure variable?

OR= AD/BC so 250x150/250x50=3 - don't take it out of the total!

Recognize renal angiomyolipoma, which is associated with *brain hamartomas & ash-leaf skin patches* in Tuberous sclerosis "32 yo woman evaluated for pain & mass in right flank. Imaging studies reveal large mass arising from right kidney & similar small masses in left kidney. Surgery to remove right-sided tumor along with right kidney is performed." "Histopathologic evaluation shows mass composed of fat, smooth muscle, & blood vessels"

Renal angiomyolipoma = benign tumor of blood vessels (angio), smooth muscle (myo), & fat (lipoma) Tuberous sclerosis = associated with angiomyolipomas = AD = cortical tumors & subependymal hamartomas in brain --> consequent seizures & cognitive disability - cardiac rhabdomyomas, facial angiofibromas, & leaf-shaped patches of skin lacking pigment (ash-leaf patches) can also occur

saddle anesthesia & loss of *anocutaneous reflex* are symptoms of cauda equina syndrome, which is associated with damage to

S2 through *S4* nerve roots

Be able to recognize recording of *increased left ventricular end-systolic volume*, which is S3 = left ventricular failure in older individuals

S3 - best heard by placing bell of stethoscope over cardiac apex with patient in left lateral decubitus - occurs early in diastole - low frequency - just after S2 Listen for 3 heard sounds! Listen to entire recording before deciding!

Recognize *serratus anterior* on CT cross section Case: "A 40-yr-old man is brought to the ER because of 1 hour of SOB and sharp pain in the chest wall. He was playing basketball and received an elbow blow to the chest. A chest X ray shows fracture of the 6th rib and right sided pneumothorax. A chest tube is inserted to drain the pleural air. Based on the CT scan below, the chest tube was most likely inserted through which of the following muscles?"

Serratus anterior - upper 8 ribs - insertion = medial border of scapula - nerve = long thoracic - action = rotates scapula upward; abducts scapula with arm and elevates it above horizontal

Located in anterior hypothalamus. Damaged causes dilute urine. Secretes ADH.

Supraoptic nucleus

72 yo woman who is right-handed is brought to the ER by her husband 3 hours after the sudden onset of difficulty speaking. She has a history of a fib. She is alert. Neuro exam shows weakness of lower 2/3 face on right. She understands verbals commands such as "raise your right arm." Her speech is not spontaneous and consists of brief phrases without intonation (parsody). Damage to which of the following labeled structures in the drawing of the brain is the most likely casue of the language findings in this patient?

broca's (recognize on brain image) - intact comprehension - *b*roca = *b*roken *b*oca - area in inferior frontal gyrus of frontal lobe - patient appears frustrated - insight intact

extensor hallucis longus is innervated by

deep peroneal nerve from *common peroneal nerve* = passes behind head of fibula & then winds around neck of fibula --> divides ito deep & superficial peroneal nerves

Recognize splice-site mutations which, would cause *incorrect splicing of pre-mRNA*

ex. = addition of *ag* - before leaving nucleus, pre-mRNA must be processes to mature mRNA by 3 post-transcriptional modifications = 5' methylguanosine capping, addition of 3' polyadenine (Poly A) tail, & splicing Spliceosomes - remove introns containing GU at 5' splice site & AG at 3' splice site --> freed 3'-OH of exon 1 forms phosphodiester bond with 5'-phosphate at splice acceptor site = joins exon 1 & 2

Contents of adductor canal

femoral vessels saphenous nerve nerve to vastus medialis

Patients with medically intractable symptoms of Parkinson disease may benefit from high-frequency deep brain stimulation of...

globus pallidus internus or *subthalamic nucleis* --> promotes thalamo-cortical disinhibition with improved mobility = inhibits firing of nuclei --> increased activity in downstream nuclei = thalamo-cortical disinhibition with improved mobility Nigrostriatal degeneration in Parkinson = excessive excitation of globus pallidus internus by subthalamic nucleus --> excessive inhibition of thalamus --> rigidity & bradykinesia

Damage to left temporal hemiretina would disrupt transmission of visual info along ...

ipsilateral optic nerve, lateral optic chiasm, optic tract, *lateral geniculate body*, optic radiations, primary visual cortex

Recognize fracture that would damage *inferior alveolar nerve*

maxillary nerve --> enters angular part of mandibula --> branch = inferior alveolar nerve

44 yo truck driver comes to ED with sudden-onset shortness of breath that started a few hours ago. Patient has no medical problems except for mild swelling of right calf over past week. He smokes 2 packs of cigarettes daily & drinks alcohol occasionally. Temp is 36.1 C (97 F), BP is 118/76 mmHg, pulse is 102/min, & respirations are 22/min. The patient's BMI is 31 kg/m^2. Cardiopulmonary exam is normal. What arterial blood gases values are most likely to be present in this patient? pH = PaO2 = PaCO2 = Plasma HCO3- =

pH = increased PaO2 = decreased PaCO2 = decreased Plasma HCO3- = normal (22-26) Pulmonary embolism - sudden-onset dyspnea in setting of recent calf swelling - dyspnea = most common symptom - risk factors = obesity, smoking, prolonged immobilization = hypoperfusion of affected pulmonary parenchyma --> redistribution of pulmonary blood flow = V/Q mismatch = *respiratory alkalosis* - bicarb level remains normal in acute phase, but metabolic compensation with renal bicarb loss occurs in 48 hours

picture frame vertebra

paget disease - *normal calcium, normal phosphorous, normal parathyroid hormone* - *increased alkaline phosphatase*

A 48-year-old woman comes to the physician because of a 1-year history of progressive ringing in her right ear. She also has felt dizzy while exercising. Neurologic examination shows dysmetria of the right upper and lower extremities. Muscle strength and somatosensory function testing of all extremities shows no abnormalities. Audiometry shows moderate hearing loss in the right ear. An MRI of the brain is most likely to show a mass compressing which of the following labeled structures in the photograph of a cross section of the brain stem?

right *inferior cerebellar peduncle* Acoustic neuroma --> tumor of right vestibulocochlear nerve --> compresses cerebellopontine angle if large enough - ipsilateral lesion = cerebellar signs

Pressure in left renal vein may become elevated via compression where vein crosses aorta beneath superior mesenteric artery. This "nutcracker effect" can cause hematuria and flank. Pressure can also be elevated in left gonadal vein, leading to formation of

varicocele

45 yo man comes to ED with 1-day history of severe dyspnea on exertion. Dyspnea has been worsening throughout day & has been occurring with progressively shorter walking distance. Patient reports no inciting trauma. He has no other med problems & takes no meds. He has 20-pack-year smoking history but does not use alcohol or illicit drugs. His BP is 110/60 mmHg & pulse is 96/min. Arterial blood gases drawn on room air show PaO2 of 54 mmHg & a PaCO2 of 26 mmHg. What is the most likely cause of blood gas abnormalities seen in this patient?

*Alveolar hyperventilation* - hypocapnia

24 yo previously healthy woman comes to hospital with 3-day history of fever, dyspnea, & productive cough of yellow sputum. Her temp is 38.3 C (102 F), BP is 110/66 mmHg, & pulse is 110/min. She has bronchial breath sounds & crackles in the right lower lung field. Lab studies are as follows: Hemoglobin = 13 g/dL Platelets = 350,000/mm^3 Leukocytes: 54,000/mm^3 Neutrophils = 65% Band form = 10% Myelocyte = 3% Metamyelocyte = 1% Lymphocytes = 15% The leukocyte alkaline phosphatase test score is elevated. What is the most likely additional finding on this patient's blood smear?

*Basophilic oval inclusions in mature neutrophils* Pneumonia with sepsis & *leukemoid reaction* = benign leukocytosis (>50,000/mm^3) - underling condition - leukocyte alkaline phosphatase can be normal or increased Peripheral smear can show *Dohle bodies = light blue (basophilic) peripheral granules in neutrophils* - blue color = ribosomes bound with RER

23-year-old man comes to office due to 3 week of malaise & fatigue. He says, "I've been sick with flu for last 3 weeks. I don't known why I'm not getting better." The patient also has profound fatigue causing difficulty with day-to-day activities. His temp is 38.4 C (101.2 F). Cardiac auscultation reveals an apical holosystolic murmur radiating to axilla, which was not heard during previous office visits. Lab evaluation shows serum creatinine of 2.3 mg/dL. Mild proteinuria & microscopic hematuria with red cell casts are present on urinalysis. What is the most likely pathogenesis of this patient's renal findings?

*Circulating immune complex-mediated injury* Infective endocarditis = young patient + constitutional (flulike) symptoms + fever + new systolic murmur = elevated serum creatinine with hematuria + proteinuria --> renal insufficiency via nephritic syndrome - *may be complicated by deposition of circulating immune complexes in glomerular capillary wall* = glomerulonephritis

Atherosclerosis lesions involving coronary arteries limit blood flow to portions of myocardium supplied by affected vessels. Admin of certain meds can cause redistribution of blood flow away from ischemic areas, exacerbating existing myocardial ischemia. A drug that causes what effects is most likely to be associated with this phenomenon?

*Coronary arteriolar dilation* - collateral circulation helps alleviate ischemia & preserve myocardial function Adenosine & Dipyridamole = selective vasodilators of coronary vessels - vasodilation of coronary arterioles in nonischemic regions - decreased perfusion pressure within collateral microvessels supplying ischemic myocardium = diverts blood from ischemic areas to nonischemic areas = coronary steal! --> hypoperfusion & potential worsening of existing ischemia

28-year-old nulliparous woman comes to clinic to be evaluated for infertility. She has been having unprotected intercourse with her husband for past 12 months & experiences pain with deep vaginal penetration. Menarche was at age 11 and her period occurs every 26 days & lasts 5-7 days. Her menstrual cycles are accompanied by moderate to severe lower abdominal pain. Pelvic exam shows normal-sized, retroverted uterus. Posterior vaginal fornix is very tender to palpation. Patient's condition most likely involves what?

*Ectopic endometrial tissues* Endometriosis / Ectopic Endometrium - presence of endometrial tissue outside uterus - risk factors = nulliparity, early menarche, prolonged menses - bleeding & shedding of extrauterine endometrium --> blood collections in ectopic locations --> hemolysis & inflammation Adhesinos - interferes with ovulation & fallopian tube function = infertility = fixed, retroverted uterus - infiltration of cul-de-sac = painful intercourse & tenderness with palpation of posterior vaginal fornix - shedding of ectopic tissue = dysmenorrhea (painful menses) - normal sized uterus = *not* adenomyosis*(would be enlarged)

42-year-old previously healthy woman comes to office due to fever & sore throat. She has no cough. Physical exam shows tonsillar exudate & a nontender cervical lymph node that measures 3.5 cm in diameter. Oral antibiotic therapy started & on a follow-up visit a week later, the patient reports that her symptoms have resolved. The previously enlarged cervical lymph node has decreased slightly in size. On several follow-up visits over the following year, the patient remains asymptomatic & the size of the lymph node fluctuates but does not disappear completely. Referral to surgeon is made & excisional biopsy of lymph node is performed. What most likely will be seen on biopsy?

*Follicular lymphoma* - most common indolent non-Hodskin lymphoma in adults - *waxing & waning* clinical course - painless lymph node enlargement or abdominal discomfort from abdominal mass - mix: cleaved & noncleaved follicle center cells in nodular pattern - t(14;18) translocation = overexpression of bcl-2 oncogene that blocks programmed cell death

9-year-old boy with beta thalassemia major comes to office for routine RBC transfusion. He was diagnosed at age 6 months and has since received numerous blood transfusions and chelation therapies. The patient has tolerated each transfusion and chelation therapy well with no immediate reactions or side effects. Vital signs are normal. On physical exam, the boy has mild frontal bossing, hepatosplenomegaly, and jaundice. A recent liver biopsy showed Kupffer cells containing coarse, yellowish-brown cytoplasmic granules. The granules are most likely composed of what?

*Hemosiderin* Chronic hemolytic anemia (beta thalassemia major) - iron overload / hemosiderosis = increased iron absorption = brown or yellow-brown pigments - should undergo chelation therapy

46-year-old woman being evaluated for irregular vaginal bleeding found to have invasive cervical carcinoma. She undergoes total abdominal hysterectomy & bilateral salpingo-oophorectomy. Pelvic lymphadenectomy was also performed, during which several enlarged nodes around pelvic vessels were resected. A week after surgery, patient beings to experience left-sided flank pain that radiates to groin. Her temp is 36.1 C (97 F), BP is 120/70 mmHg, & pulse is 84/min. On physical exam, there is a ballotable left flank mass. What most likely accounts for this physical exam finding?

*Hydronephrosis* Flank pain radiating to groin with ballotable flank mass that develops within week of pelvic surgery = *ureteric obstruction* - ureter anterior to iliac vessels = area of resection of pelvic nodes - vulnerability to injury during pelvic surgery Unintentional ureteral ligation = obstruction with hydronephrosis & flank pain via distention of ureter & renal pelvis

29-year-old nulliparous woman with HIV comes to office for her first gynecological exam. Patient acquired HIV from her mother at birth and has been noncompliant with health maintenance visits. Menarche was at age 10, cycles occur every 28 days, & her last menstrual period was 2 weeks ago. Patient has 1 lifetime male partner with whom she has been sexually active for 7 years; they use condoms consistently. Her mother had cervical cancer at age 46 & died of AIDS-related complications at age 48. Patient drinks 3-4 cans of beer each night & does not use tobacco or illicit drugs. Papanicolaou test reveals high-grade cervical dysplasia. What is the strongest risk factor for cervical dysplasia in this patient?

*Immunosuppression* Strongest risk factor for cervical dysplasia / cervcal intraepithelial neoplasia & carcinoma = HPV type 16 or 18 - cervical cancer is rare in immunocompetent women Individuals with HIV - unable to mount immune response against HPV due to immunosuppression from T cell deficiency - HPV DNA becomes incorporated into epithelial cells

Noncontrast CT & brain MRI are consistent with diagnosis of cavernous hemangioma. This patient is at greatest risk of developing what complications?

*Intracerebral hemorrhage* Cavernous hamangiomas - vascular malformations (sporadic or familial) - most commonly occur within brain parenchyma above cerebellar tentorium - clusters of dilated, thin-walled capillaries with little or no intervening nervous tissue - often have *seizures* - tendency to bleed = neuro symptoms = hyperdense/bright mass on head CT = mulberry-like = purple vascular clusters

Postoperative evaluation shows that the tumor has invaded several mesenteric lymph nodes & is expressing epidermal growth factor receptor (EGFR). Adjuvant therapy with EGFR inhibitor is being considered. An activating mutation in what will most likely make the therapy ineffective?

*KRAS protein* = proto-oncogene that encodes GTP-binding protein KRAS mutation causing anti-EGFR resistance - metastatic colon cancers - constitutive downstream signaling, even in absence of EGFR stimulation = increased cell proliferation - resistant to anti-EGFR therapy (cetuximab & panitumumab)

54 yo man comes to ED with severe fatigue & dyspnea. He has long history of progressively worsening heart failure that has been resistant to Hodgkin's disease & has been in remission every since. Patient is admitted to hospital, but his condition continue to deteriorate despite aggression therapy. He dies 3 days later & an autopsy is performed. Gross inspection of his heard shows dense, thick fibrous tissue in pericardial space between visceral & parietal pericardium. What signs of this patient would most likely have been detected during physical exam of this patient?

*Kussmaul sign* = paradoxical rise in JVP - bc volume-restricted right ventricle is unable to accommodate inspiratory increase in venous return Constrictive pericarditis - thick fibrous tissue in pericardial space - dense-rigid pericardial tissue encases hear & restricts ventricular filling = low cardiac output = right-sided heart failure resistant to meds - JVP almost always increased

65-year-old man dies while hospitalized for dyspnea. His wife reports several prior episodes of dyspnea & cough. He has a history of HT & smoked a pack of cigarettes daily for 38 years. He immigrated to the United States 20 years ago. Light microscopic examination of his lung reveals macrophages containing golden cytoplasmic granules that turn dark blue with Prussian blue staining. What conditions is most likely associated with this patient's microscopic findings?

*Left ventricular dysfunction* Heat failure due to left ventricular dysfunction - Prussian blue stain detects intracellular iron --> golden cytoplasmic granules in macrophages that turn blue with Prussian blue staining = hemosiderin laden macrohpages (siderophages) Presence of hemosiderin-laden macrophages in pulmonary alveoli = chronic elevation of pulmonary capillary hydrostatic pressure = via left-sided heart failure

46-year-old Caucasian male presented with abdominal pain is diagnosed with rare vascular tumor. This type of tumor oftentimes assocaited with past arsenic or polyvinyl chloride exposure. Immunohistochemical staining of the tumor cells is positive for the CD 31 cell marker. The patient most likely has what conditions?

*Liver angiosarcoma* - arsenic (exposure to pesticides), thorotrast (former radioactive contrast medium), polyvinyl chloride (plastic widely used in industry) - PECAM = member of Ig family of proteins = expressed on surface of endothelial cells = leukocyte migration through endothelium

Coronary CT angiography reveals several nonobstructive atherosclerotic plaques in coronary arteries. One plaque in the proximal LAD artery appears extensive, had a large hypodense core, & occupies 40% of lumen. No intervention is performed. One year later, patient comes to ED with acute severe chest pain & is found to have thrombotic occlusion of proximal LAD artery. High intraplaque activity of what enzymes most likely resulted in this patient's myocardial infarction?

*Metalloproteinases* - acute coronary syndrome usually occurs via plaque rupture --> superimposed thrombosis & vessel occlusion - balance of collagent synthesis & degradation determines mechanical strength of cap - activated macrophages infiltrating atheroma = breakdown of extracellular matrix proteins (collagen) by secreting *metalloproteinases* - ongoing intimal inflammation can destabilize mechanical integrity of plaque via release of metalloproteinases = plaque rupture & consequent acute coronary syndrome

50 yo woman with periodic reddening of her skin that is starting to become bothersome. Redness involves mainly face & neck & is accompanied by mild warmth. Episodes initially lasted only a few minutes, but now they sometimes exceed 20 minutes. Patient has also had persistent watery diarrhea & associated abdominal cramping for last several months. Physical exam shows several, purple vascular lesions surrounding her nose. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) over 24 hours is increased. Abdominal imaging shows tumor in SI. What is most likely responsible for this patient's condition?

*Metastatic carcinoid* Carcinoid tumor - if *metastasizes to liver* --> vasoactive substance bypass liver & enter systemic circulation = carcinoid syndrome by bypassing first-pass metabolism

4-year-old girl develops acute-onset colicky abdominal pain, vomiting, & loose bloody stools during fam vacation. She was treated with supportive care & began to feel better. Few days later, her parents bring her to the ED because she has urinated only once in the past 10 hours & the urine was red. Physical exam shows conjunctival pallor but is otherwise normal. Lab studies are as follows: Hemoglobin = 7.8 g/dL Platelets = 80,000/mm^3 Creatinine = 1.7 mg/dL Urinalysis shows proteinuria & hematuria. What mechanism is the most likely cause of this patient's condition?

*Microthrombi in small blood vessels* Hemolytic uremic syndrome (HUS) = major cause of acute renal failure in young children = via Shiga toxin (verotoxin)-producing organisms = E coli O157:H7, Shigella dysenteriae - injured endothelium of preglomerular arterioles & glomerular capillaries = platelet activation & aggregation & formation of microthrombi - platelet consumption = thrombocytopenia (platelets < 140,000/mm^3) = schistocytes = microangiopathic hemolytic anemia (conjunctival pallor) - extensive damage to renal vasculature = acute kidney injury

64-year-old man comes to office due to persistent back pain, constipation, & easy fatigability for last several months. BP is 115/75 mmHg & pulse is 88/min. Patient has dry mucus membranes. Lab results are as follows: Hemoglobin = 8.6 g/dL MCV = 92 gL BUN = 68 mg/dL Creatinine = 3.8 mg/dL Total protein = 8.9 g/dL Albumin = 4.1 g/dL Renal biopsy is performed & light microscopy shows atrophic tubules, many of which containg large, obstructing, intensely eosinophilic casts. What is the most likely diagnosis?

*Multiple myeloma* - fatigability (anemia), constipation (hypercalcemia), bone pain (bone lysis via osteoclast-activating factor by myeloma cells), elevated serum protein (monoclonal proteins), renal failure Myeloma cast nephropathy / myeloma kidney - excess excretio of free light chains (Bence Jones proteins) - light chains ppt with Tamm Horsfall protein = casts = tubular obstruction & epithelial injury = impaired renal function

Multiple Sclerosis is an inappropriate immune response directed against what neural structures?

*Oligodendrocytes* MS = autoimmune = young women (<50) = neuro deficits = disseminated in time & space - common initial manifestation = optic neuritis = monocular visual loss with pain on eye movement & afferent pupillary defect - MRI = white matter lesions scattered throughout brain &/or spinal cord with predilection for subcortical periventricular regions - helper T cells abnormally resct to Ags in myelin = release of inflammatory cytokines (IFN-gamma) --> infiltration of destructive macrophages/microglia & leukocytes

pericardial knock

= constrictive (*chronic*) pericarditis = brief, high frequency, precordal sound = early diastole = earlier than S3 ventricular gallop = requires months or years to develop

MRI reveals acute subcortical infarct in left internal capsule. Six months later, what findings is most likely to be observed in the affected pyramidal tracts of this patient?

*Persistent myelin debris* Wallerian degeneration - when axon is damaged = axonal degeneration & breakdown of myelin sheath distal to site of injury - degeneration of axon usually begins within few days after lesion onset CNS - phagocytic macrophages/microglia recruited more slowly because of BBB - slow removal = myelin debris = persists for years in degenerating tracts & suppresses axonal growth via myelin-associated inhibitory factors - astroycytes can release inhibitory molecules & proliferate in weeks to months following injury = glial scar that acts as barrier to axon regeneration

46-year-old man hospitalized with diabetic ketoacidosis. He is administered IV fluids & an insulin drip, & lab testing is ordered. In the morning, the on-call physician hands off the patient to the day shift physician, who arrives an hour late due to emergency at his nighttime moonlighting job. The handoff info includes status of patient & instructions to check electrolytes & calculate his anion gap. The physician performs inpatient rounds & then sees his usual clinic outpatients in the afternoon, but he neglects the patient's anion gap. The patient subsequently develops worsening acidosis requiring intubation for respiratory distress. What is the most likely cause of this adverse outcome?

*Physician fatigue* Sleep deprivation - extended work hours of attending physician are unregulated

29-year-old woman comes to office due to intermittent nipple discharge for past several weeks. Patient has never been pregnancy and has been having unprotected intercourse with her husband. Menarche was at age 12. For past year, menses occurred every 2-3 months but stopped 6 months ago. Her mother was diagnosed with metastatic breast cancer at age 60 and passed away recently. The rest of the exam is normal. Urine beta-hCG is negative. What is the most likely diagnosis in this patient?

*Pituitary adenoma* / Prolactinoma - proliferation of lactotrophs Hyperprolactinemia - galactorrhea, amenorrhea, loss of libido, infertility in women - if patient with galactorrhea has elevated serum prolactin, gold standard = MRI of brain

46-year-old previously healthy woman comes to ED due to 4 days of intermittent fever, abdominal pain, & vomiting. For past 2 days she has also had decreased urine output, skin rash, & progressive lethargy. Her temp is 38.3 C (101 F), BP is 130/80 mmHg, & pulse is 100/min. There is a scattered petechial rash, facial puffiness, & 1+ bilateral pedal edema on physical exam. Lab studies show Hemoglobin of 8.9 g/dL with elevated reticulocyte count & a platelet count of 26,000/mm^3. Bleeding timeis prolonged; prothrombin time & activated partial thromboplastin time are normal. The peripheral blood smear shows schistocytes & reduced platelets with presence of giant forms. Blood urea nitrogen is 46 mg/dL & serum creatinine is 2.3 mg/dL. Urinalysis is positive for proteinuria & hematuria. What is most likely to be seen on renal biopsy?

*Platelet-rich thrombi in glomeruli & arterioles* Pentad of fever, neuro symptoms (progressive lethargy), renal failure, anemia, thrombocytopenia in setting of GI illness = *thrombocytopenic thrombotic purpua-hemolytic uremic syndrome (TTP-HUS)* = thrombotic microangiopathy syndrome = *platelet activation* in arterioles & capillaries = diffuse microvascular thrombosis = microangiopathic hemolytic anemia & schistocytes = thrombocytopenia = normal PT & aPTT

2-day-old boy develops abdominal distention & refuses to breastfeed. He was born via normal spontaneous vaginal delivery at 39 weeks gestation to primigravid mother. Exam shows significant abdominal distention with palpable intestinal loops. Rectum has no stool & rectal tone is normal. During exam, infant has several episodes of dark green emesis. Plain films of abdomen show air-fluid levels & small bowel dilation. Contrast enema fails to relieve obstruction, & patient is taken for emergency laparotomy, which shows inspissated, green fecal mass obstructing distal ileum. Infant recovers from surgery uneventfully. What will be the most likely cause of mortality in this patient?

*Pneumonia* Bowel obstruction = abdominal distention + x-ray Meconium ileus = green inspissated mass (dehydrated meconium) in distal ileum = CF specificity = abnormally viscous mucus in small bowel CF = pneumonia, bronchiectasis, cor pulmonale

28-year-old woman comes to ED with acute-onset abdominal pain, nausea, & confusion. She has no significant past med history & does not use tobacco or alcohol as they have made her feel sick in the past. Serum lipase & liver function tests are within normal limits. CT scan of abdomen shows no abnormalities. IV dextrose is administered & her symptoms improve significantly. Dextrose infusion most likely improved this patient's condition by affecting what pathways?

*Porphyrin synthesis* Acute intermittent porphyria (AIP) = AD = porphobilinogen (PBG) deaminase deficiency = accumulation of early heme pathway intermediates (PBG & delta-aminolevulinic acid [ALA]) = acutely: GI & neuro symptoms - abdominal pain, vomiting, peripheral neuropathy, neuropsychiatric - *reddish urine that darkens on exposure to light & air due to oxidation of excess PBG* - treatment = avoidance of alcohol, smoking, other CYP450-inducing drugs; IV heme admin & carb loading (dextrose infusion)

64-year-old male brought to ER with severe chest pain, diaphoresis & mild shortness of breath. Following initial evaluation, patient is taken to cardiac catheterization lab & near-total occlusion of LAD coronary artery is detected. The vascular endothelium secretes what substances to inhibit platelet aggregation:

*Prostacyclin* / Prostaglandin I2 = fam of eicosanoids = paracrine properties = inhibits platelet aggregation & adhesion to vascular endothelium = vasodilates, increases vascular permeability, stimulates leukocyte chemotaxis

72-year-old man brought to ED due to diarrhea & vomiting for last 24 hours. Patient's daughter states that he has been unable to take in much fluid after becoming sick. He has HT treated with hydrochlorothiazide, which he has not taken since the onset of symptoms. On exam, his mucous membranes are dry. BP is 90/60 mmHg & pulse is 105/min. Urinalysis shows concentrated urine with specific gravity of 1.04. What changes in RPF, GFR, & FF are most likely to be present in this patient as compared to the normal state?

*RPF decreased* *GFR decreased* *FF increased* FF = ratio of GFR to RPF Hypovolemic patient via profuse diarrhea & vomiting - decline in circulating blood volume sensed by arterial & cardiac baroreceptors --> systemic arteriolar vasoconstriction --> renal vasoconstriction further lowers RPF, which is already decrease - Stimulated Ang II preferentially constricts efferent glomerular arteriole = increased hydrostatic pressure in glomerular capillaries *Decrease in GFR less pronounced than decreased in RPF = increased FF*

36-year-old woman brought to ED with sudden-onset right side weakness and speech difficulty. During last 3 weeks, patient has experienced progressive fatigue, malaise, & low-grade fevers. Despite symptoms, she did not seek med attention & did not take any meds. She has dental extraction 5 weeks ago, which was uncomplicated. Patient has never previously been significantly ill or hospitalized. She works as a receptionist at a legal firm & has never traveled outside the US. She does not use tobacco, alcohol, or illicit drugs. Patient is admitted to the hospital, but despite adequate resuscitative measures, she dies 2 hours later. Gross autopsy shows large, friable irregular masses attached to atrial surface of a valve. What underlying conditions most likely predisposed this patient to her presenting disease?

*Regurgitant mitral valve prolapse* Subacute infective endocarditis complicated by embolic stroke - strep viridans after dental extraction

42-year-old woman brought to hospital due to right-sided weakness & difficulty speaking. She has longstanding history of diastolic murmur, but her medical follow-up has been poor. She does not use tobacco, alcohol, or illicit drugs. A CT scan of brain reveals large ischemic stroke involving left middle cerebral artery distribution. Patient dies 2 days later due to progressive neuro deterioration. At autopsy, exploration of left atrium shows diffuse fibrous thickening & distortion of mitral valve leaflets, commissural fusion at leaflet edges, & narrowing of mitral valve orifice. This finding is most likely the result of what condition?

*Rheumatic fever* Mitral stenosis due to Rheumatic heart disease - latency period of 10-20 years between initial episodes of rheumatic fever & symptomatic MS - most patients menifest during 4th or 5th decades of life - can cause atrial enlargement --> atrial fibrillation &/or atrial mural thromboses --> embolic stroke Mitral stenosis = loud first heart sound = early diastolic sound (opening snap) - followed by mid-diastolic murmur from turbulent flow across mitral valve

26-year-old woman, gravida, para 1, comes to office for routine exam. She noticed new facial hair over last few months & thinks her voice is deeper. Her last menstrual period was 5 months ago. Patient's mother died from invasive lobular breast carcinoma at age 60. Physical exam is significant for coarse facial hair, & pelvic exam reveals clitoromegaly confirms a large ovarian cyst. What is the most likely diagnosis?

*Sertoli-Leydig tumor* = large adnexal mass with amenorrhea & virilization = hirsutism, clitoromegaly, deeper voice = via increased testosterone secretion by rare sex cord-stromal tumor - usually young women - hollow or solid tubules lined by round Sertoli cells surrounded by fibrous stroma

42-year-old man comes to office with blood in his urine, fatigue, & nasal congestion for last few months that has been unresponsive to conventional therapy. He has no other chronic med problems. Physical exam shows edema around ankles, hands, & face. Lab results show BUN of 20 mg/dL & serum creatinine of 3.8 mg/dL. Urinalysis shows moderate proteinuria & a large amount of RBCs with RBC casts. Kidney biopsy is performed. Light microscopy reveals cellular proliferation, focal necrosis, & crescent formation of most glomeruli. On immunofluorescent microscopy, there are no immunoglobulin or complement deposits. What additional findings is most likely to be present in this patient?

*Serum antineutrophil cytoplasmic antibodies* Crescent formation = Rapidly progressive (crescentic) glomerulonephritis: Pauci-immune rapidly proliferative glomerulonephritis - via antineutrophilic cytoplasmic Abs-associated vasulitides (granulomatosis with polyangitis, microscopic polyangiitis) - absence of Ig or complement deposits - renal failure + pulmonary (cough, hemoptysis) + upper respiratory symptoms (mucosal ulceration, chronic sinusitis) via underlying vasculitis

65-year-old man comes to office due to several weeks of nonproductive cough. The patient also has anorexia & unintentional weight loss. His med history includes hypothyroidism due to Hashimoto thyroiditis & a 50-pack-year smoking history. Exam shows enlarged, right supraclavicular lymph node. An imaging study shows large mediastinal mass causing tracheal deviation. Histopathology of lymph node after biopsy demonstrates clusters of small, ovoid cells with scant cytoplasm & a high mitotic count. Immunohistochemical staining is positive for chromogranin. The patient most likely suffers from what conditions?

*Small cell carcinoma* Small cell lung cancer / undifferentiated / oat cell carcinoma - 10-20% of malignant lung cancers - smoking - centrally located - from primitive cells of basal layer of bronchial epithelium = round or oval cells with scant cytoplasm & large hyperchromatic nuclei = sheets or clusters = abundant mitoses = neuroendocrine differentiation Neuroendocrine markers - neuron-specific enolase - *chromogranin* - synaptophysi - some cells have secretory granules in cytoplasm

What would most indicate left-sided heart failure in a patient?

*Supine dyspnea that is relieved by sitting up* - supine dyspnea relieved by sitting up = orthopnea = specific sign of advanced left-sided heart failure - via acute exacerbation of baseline pulmonary edema that occurs when central venous, pulmonary venous & cardiac filling pressures are increased by redistribution of blood that has been pooled in dependent veins back into central circulation

32-year-old woman comes to office for evaluation of breast lump. She noticed lump a few months ago but thinks it might be getting larger. Patient has history of right lower limb amputation at age 17 due to osteosarcoma. Patient's mother died of adrenal tumor, & her younger sister died of leukemia. Exam of left breast shows 5-cm, firm immobile mass with irregular borders. What gene mutations is most likely etiology for this patient's condition?

*TP53* History of sarcoma, leukemia, adrenal, & breast cancer = Li-Fraumeni syndrome - cancers of brain are common - AD mutation of TP53 = tumor suppressor protein p53 - genetically predisposed to cancer dev't at young age = 2-hit hypothesis

68-year-old Caucasian male presents with chewing difficulty & persistent headaches of recent onset. On physical exam, there is tenderness over patient's temples. You proceed with artery biopsy. Morphologic changes observed in this patient's arteries are most similar to what conditions?

*Takayasu arteritis* Giant Cell (Temporal) Arteritis (GCA) - jaw claudication - temporal biopsy = *granulomatous inflammation of media* - patients older than 50 Takayasu arteritis - medial granulomas - aortic arch mostly - females less than 40 Patient's age = differential

52-year-old man comes to ED via vague chest pain & cough. He immigrated to US from Taiwan 20 years ago. Temp is 37.1 C (98.8 F). Physical exam reveals decrescendo-type diastolic murmur over right sternal border. Pulmonary auscultation reveals normal breath sounds with no wheezes or rales. Abdominal exam shows no organomegaly. Serum fluorescent treponemal antibody absorption testing is positive. Chest x-ray reveals mediastinal widening. Pathologic process most likely responsible for this patient's symptoms starts as what?

*Vasa vasorum obliteration* - murmur = aortic regurgitation + mediastinal widening = aortic aneurysm that has dilated aortic annulus Syphilis = luetic aneurysm = tertiary syphilis Tertiary syphilis = vasa vasorum endarteritis & obliteration - aneurysmal dilation of thoracic aorta can extend to involve aortic valve ring - uncommon in US

56-year-old woman brought to ED due to several days of progressive dyspnea, productive cough, & fever. Today, her son found her very short of breath & obtunded. The patient has history of HT, type 2 diabetes mellitus, & long-standing RA. Exam reveals bilateral pneumonia & severe respiratory distress. Patient is lethargic without focal neuro deficits. Urgent endotracheal intubation is performed for mechanical ventilation, & the patient is started on broad-spectrum antibiotics. Repeat exam 2 hours later shows that she has developed areflexic, flaccid paralysis of all extremities. What is the most likely cause of neuro deficits in this patient?

*Vertebral subluxation* RA --> underwent urgent endotracheal intubation - long-standing RA often involves cervical spine = joint destruction with vertebral malalignment (subluxation) - atlantoaxial joint most often involved Cervical subluxation = neck pain, stiffness, neuro findings (sensory loss, muscle weakness) - extension of neck during endotracheal intubation can worsen subluxation = acute compression of spinal cord &/or vertebral arteries

Friedreich ataxia has clinical manifestations that closely resemble what disease?

*Vitamin E deficiency* - hemolysis & neurologic dysfunction (via free radical damage of cell membranes) - ataxia (degeneration of spinocerebellar tracts), loss of deep tendon reflexes (peripheral nerve degeneration)

Vitiligo is due to ...

*absence of melanocytes in skin* Vitiligo - partial or complete loss of epidermal melanocytes - 2nd-3rd decade of life - flat, well-circumscribed macules & patches of absent pigment - complete absent of melanin pigment - autoimmunity - correlation with other autoimmune disorders = type I DM, pernicious anemia, Addison disease, autoimmune hepatitis, Graves' disease, autoimmune thyroiditis

Guillan-Barre syndrome is demyelination accompanied by

*endoneural inflammatory infiltrate* - demyelination causes ascending flaccid paralysis & areflexia - segmental demyelination of peripheral nerves - paralysis of respiratory muscles can occur! - paralysis of CNs can occurs, such as CN VII/Bell's palsy

DIC in pregnancy patient most likely caused by

*release of tissue factor into maternal circulation* Risk factors of DIC - placental injury (placental abruption), sepsis, postpartum hemorrhage, acute fatty liver of pregnancy, amniotic fluid embolism In pregnancy, DIC is mediated by tissue factor (thromboplastin) - in high concentration in placental trophoblast - tissue factor released from sites of placental injury --> initiates coagulation cascade, excessive production of thrombin, widespread intravascular fibrin deposition & fibrinolysis - clotting factors & platelets rapidly consumed = profound bleeding from incision sites, IV line sites, mucosal surfaces (gums, vagina)

42-year-old man hospitalized with fever & persistent sore throat. On physical exam, his temp is 38.3 C (101 F), BP is 120/80 mmHg, pulse is 94/min, & respirations are 16/min. There are several bruises on his trunk, & blood is oozing from his IV catheter venipuncture sites. His blood fibrinogen level is 110 mg/dL (normal 150-400 mg/dL). Bone marrow biopsy shows predominance of immature myeloid cells with azurophilic needle-shaped cytoplasmic granules. Chromosomal analysis of these immature cells is most likely to shows what abnormalities?

*t(15;17)* DIC in setting of APL - subtype of AML = promyelocytes (immature myeloid cells) = Auer rods (fused lysosomal granules) - decreased fibrinogen levels - t(15;17) = fusion of retinoic acid receptor-alpha (RARA) gene to PML gene = AML M3 in FAB classification

RBC fragments, burr cells, & helmet cells consistent with

*traumatic hemolysis* - via microangiopathic hemolytic anemia or mechanical damage (prosthetic valve) Burr cells can occur as artifact or in association with... - uremia - pyruvate kinase deficiency - microangiopathic hemolytic anemia - mechanical damage

Recognize *sarcoidosis* "43 year old African American male man comes to physician complaining of malaise, nocturnal fevers, & cough for last several weeks. He has also lost 4.5 kg (10 lb) over last month. He has no appreciable past med history & has not traveled recently. Patient has spent last 10 years working as respiratory therapist at large urban hospital. His chest x-ray is shown." "Palpable lymph node in supraclavicular bed is biopsied & pathology reveals well-formed, non-caseating granulomas."

- African American with constitutional symptoms - bilateral adenopathy (arrows) - pulmonary complaints - enlarged lymph nodes

Normal morphological changes in aging heart

- decrease in left ventricular chamber apex-to-base dimension - dev't of sigmoid-shaped ventricular septum - myocardial atrophy with increased collagen deposition - accumulation of cytoplasmic lipofuscin pigment within cardiomyocytes = brownish perinuclear cytoplasmic inclusions

Recognize basophilic stipping, associated with *lead/metal poisoning*

- industrial workers - young children ingesting paint chips

Recognize *strawberry (infantile) hemangioma*

- variant of capillary hemangioma - most common benign vascular tumor in children - appear during first days or weeks after birth - grow rapidly during first one-two years of life - regress by 5-8 years of age - thin-walled blood vessels with narrow lumens filled with blood & separated by CT

Recognize *ecchymosis*

= cutaneous or subcutaneous collection of extravasated blood = at least 1 cm in diameter = frequently indicate deep hemorrhage (hematoma) via bony fracture, ligamentous rupture, or muscular injury = don't blanch under pressure because RBCs not contained within vasculature - often pass through evolution of color change = estimation of age of injury

Recognize *uric acid stones*, which has an underlying mechanism of *increased hydrogen ion excretion in kidney*

= yellow/brown, diamond- or rhomboid-shaped crystals = radiolucent = cannot be visualized on plain radiography Chronic diarrhea or Colectomy - reduced bicarb reabsorption from gut --> chronic metabolic acidosis - *kidneys compensate by increasing excretion of hydrogen ions & reabsorption of bicarbonate in collecting ducts* --> lowers urinary pH (acidic urine) = increased conversion of soluble urate salts into insoluble uric acid *Primary site of uric acid precipitation = collecting ducts due to low urine pH*

Recognize *senile amyloidosis*

Diastolic heart failure - progressive exertional dyspnea - edema - ascites - elevated JVP with rapid y decent, prominent S4 - left atrial enlargement - LVH - normal ejection fraction Restrictive cardiomyopathy Cardiac amylosis = amorphous & acellular pink material

What sets of diagnostic findings would be most consistent with isolated diastolic heart failure? Left ventricular end-diastolic pressure = Left ventricular end-diastolic volume = Left ventricular ejection fraction =

Left ventricular end-diastolic pressure = increased Left ventricular end-diastolic volume = normal Left ventricular ejection fraction = normal Diastolic heart failure = common cause of acute decompensated heart failure = *normal left ventricular ejection fraction (LVEF, > 50%) & end-diastolic volume in setting of increased LV filling pressures* = decreased ventricular compliance

Abrupt-onset gross hematuria in otherwise healthy patient with fam history of sickle cell disease suggests

renal *papillary necrosis* (RPN) - via underlying sickle cell trait - gray-white or yellow necrosis of distal two-thirds of renal pyramids macroscopically - coagulation necrosis - symptoms via sloughed papillae = dark/bloody urine - colicky flank pain (via ureteral obstruction) RPN conditions - sickle cell - analgesic nephropathy - diabetes mellitus