Uworld 46

Front 1

Rabies

-presentation: fever, severe agitation, disorientation, auditory hallucinations, excessive salivation.

Back 1

-rhabdoviridae (rabies) are single-stranded RNA viruses enveloped by a bullet-shaped

-capsule that is studded by glycoprotein spikes that bind to nicotinic ACETYLCHOLINE receptors.

-once deposited in a wound, virus stays local for period of days/weeks before binding to acetylcholine receptors on peripheral nerve axons and traveling retrograde to CNS.

-clinical presentation of agitation, disorientation, pharyngospasm, and photophobia leading to coma and death is strongly suggestive of rabies encephalitis

Front 2

Viral cellular receptors

Back 2

-cytomegalovirus binds to cellular integrins

-Epstein-Barr virus binds to CR2 (CD21)

-HIV binds to CD4 and CXCR4/CCR5

-Rabies binds to nicotinic acetylcholine receptor

-Rhinovirus binds to ICAM-1 (CD54)

Front 3

Psoriasis treatment

Back 3

-treatment of psoriasis ranges from topical therapies to systemic treatment with conventional and biological drugs

-topical vitamin D analogs (calcipotriene, calcitrol, and tacalcitol) bind to the vitamin D receptor and inhibit keratinocyte proliferation, and stimulate keratinocyte differentiation.

-i.e., calcipotriene = treatment of psoriasis that activates a nuclear transcription factor

Front 4

Acute tubular necrosis

Back 4

-acute tubular necrosis can develop following internal hemorrhage (e.g., after MVA)

-clinical course of ATN may be divided into initiation, maintenance (oliguric) and recovery phases.

-initiation: renal tubule cell damage begins to evolve, GRF falls, urine output decreases

-maintenance (oliguric) phase: renal tubule injury is established, and GFR stabilizes far below normal; urine output is low/absent.

--LM in maintenance stage shows granular casts in the tubular lamina
--flattening of tubular epithelial cells and tubular epithelial necrosis with denudation of tubular basement membrane also seen.

-recovery phase of ATN is characterized by re-epithelialzation of tubules
--polyruria and gradual normalization of GFR occur, leading to complete restoration of renal function in most patients.

-most patients with ATN experience tubular re-epithelialization and regain renal function

-when ATN is associated with multi-organ failure, renal function may be permanently impaired.

Front 5

N-acetylglutamate

Back 5

-N-acetylglutamate is an essential activator of carbamoyl phosphate synthase I

-N-acetylglutamate is formed by the enzyme N-acetylglutamate synthase from the precursors acetyl-CoA and glutamate

Front 6

Aortic regurgitation

Back 6

-"water hammer pulses" and head-bobbing with each heart beat (de Musset sign) are characteristic findings in patients with aortic regurgitation

Front 7

Chronic renal allograft rejection

Back 7

-chronic renal allograft rejection can manifest months to years after transplantation

-mediated by recipient antibodies to graft endothelium formed after engraftment, causing an OBLITERATIVE INTIMAL SMOOTH MUSCLE HYPERTROPHY and FIBROSIS OF CORTICAL ARTERIES, i.e., obliterative vascular necrosis

-vs. hyperacute rejection involves pre-formed recipient anti-donor endothelial antibodies, causing immediate vascular fibrinoid necrosis, neutrophil infiltration, infarction of graft

-vs. acute rejection can be cellular (causing interstitial mononuclear infiltrate) or humoral (causing a graft vasculitis).

Front 8

Skeletal muscle contraction

Back 8

-during skeletal muscle contraction cycle, ATP binding to myosin causes release of myosin head from its binding site on the actin filament

Front 9

Hyper-prolacinemia

Back 9

-hyper-prolactinemia causes hypogonadism, which leads to reduced estrogen in women.

-low estrogen due to any cause is a risk factor for accelerated bone loss, i.e., osteoporosis.

Front 10

Prolonged ACTH stimulation

Back 10

-ACTH is the major trophic hormone of the zone fasciculata and reticular is (vs. zona glomerulosa primarily regulated by angiotensin II)

-prolonged ACTH stimulation causes HYPERPLASIA of zone fasciculata and reticular is, resulting in excessive cortisol production (Cushing syndrome)

Front 11

COPD and erythropoietin

Back 11

-COPD can cause hypoxia sufficient to stimulate increased erythropoietin production by the cortical cells of the kidney

Front 12

Vertigo

-presentation: 32-yo woman with five episodes of vomiting in last year, with feeling that room is spinning and balance loss

-Romberg sign is negative and there is stability during the tandem walk.

Back 12

-vertigo is a sensation of excessive motion compared to physical reality

-vertigo is most commonly due to dysfunction within the vestibular system of the inner ear

Front 13

Left atrium

Back 13

-left atrium forms majority of posterior surface of heart, and resides adjacent to esophagus.

--left atrium can be analyzed via trans-esophageal ultrasound

--enlargment of the left atrium can compress the esophagus and cause dysphagia

Front 14

Descending throacic aorta

Back 14

-descending thoracic aorta lies posterior to esophagus and left atrium

-this position permits clear visualization of descending aorta via trans-esophageal echocardiography, allowing for detection of abnormalities such as dissection or aneurysm.

Front 15

Peau d'orange

-presentation: 47-yo female with yellow-red skin rash on chest, plus brawny induration and pitting over right breast

Back 15

-Peau d'orange describes présence of pitting edema in subcutaneous breast tissue, accompanied by skin thickening around exaggerated hair follicles

-this pitting edema occurs when neoplastic cells plug the dermal lymphatic channels

Front 16

Pyruvate dehydrogenase

Back 16

-hypoxia-induced lactic acidosis is caused by a low activity of pyruvate dehydrogenase (oxidative phsophorylation pathway toward acetyl CoA and Krebs), and a high activity of lactate dehydrogenase (anaerobic pathway toward lactic acid)

Front 17

Sporothrix schenckii

Back 17

-Sporothrix schenckii is dimorphic: yeast in beast, mold in cold

-seen with gardening, thorn prick ("rose-gardener disease)

-pustules, ulcers, subcutaneous nodules along the lymphatics

-culture shows branching hyphae, biopsy shows round CIGAR-SHAPED budding yeasts

Front 18

Coccidi oides immitis

Back 18

-Coccidioides immitis is dimorphic: yeast in beast, mold in cold

-seen in SW states (desert) – mold form present in soil

-pulmonary form: flu-like illness, with cough and erythema nododum

-disseminated for: affects skin, bones, lungs

-culture: hyphae
-biopsy (at 37ºC) forms thick-walled spherules filled with endospores

Front 19

Histoplasma capsulatum

Back 19

-histoplasma capsulatus is dimorphic: yeast in beast, mold in cold

-Ohio and Mississippi river valleys – in soil, bird/bat droppings (chicken coops, caves)

-pulmonary: similar to tuberculosis (lung granulomas with calcifications)
-disseminated: lungs, spleen, liver

-culture (25ºC): branching hyphae
-biopsy: oval yeast cells WITHIN MACROPHAGES

Front 20

Blastomyces dermatitidis

Back 20

-Blastomyces dermatitidis is dimorphic: yeast in beast, mold in cold

-in Ohio and Mississippi River valleys and Great Lakes region – found in soil

-pulmonary: pneumonia
-disseminated form: common and severe

-culture: branching hyphae
-biopsy, large round yeasts with DOUBLY REFRACTILE WALL and single BROAD-BASED BUD

Front 21

Paracoccidioides brasiliensis

Back 21

-Paracoccidioides brasiliensis is dimorphic: yeast in beast, mold in cold

-found in central and south America

-mucocutaneous: chronic mucocutaneous or cutaneous ulcers, which can progress to lymph nodes and lungs

-culture: multiple bastoconidia

-biopsy: cells covered in budding blastoconidia

Front 22

pCO2 and cerebral vasodilation

Back 22

-pCO2 is the most potent cerebral vasodilator

-CO2 decreases cerebral vascular resistance, leading to increased cerebral perfusion and increased intra-cranial pressure

-patients with COPD usually have low pO2 (hypoxia) and high pCO2 (hypercapnia)

--thus, their cerebral circulation is likely to be increased

Front 23

Antibiotic effective against pseduomonas aeruginosa

Back 23

-anti-pseudomonal penicillins: ticarcillin, piperacillin

-cephalosporins: ceftazidime (3rd generation), cefepime (4th generation)

-aminoglycosides effective against P aeruginosa: amikacin, getamicin, tobramycin

-fluoroquinolones effective against P aeruginosa: ciprofloxacin, levofloxacin

-monobactam effective against P aeruginosa: aztremonam

-carbapenems against P aeruginosa: impipenem, meropenem

Front 24

Protein M

Back 24

-protein M is the major virulence factor for Streptococcus pyogenes

-protein M inhibits phagocytosis and complement activation; mediates bacterial adherence; and is the target of type-specific humoral immunity to S. pyogenes

-i.e., resistance of group A Streptococci to phagocytic killing can be overcome by adding antibodies to Protein M

Front 25

Secondary structure of proteins

Back 25

-hydrogen bonds are principal stabilizing force in secondary structure of proteins

-vs. tertiary structure, which is stabilized by not only hydrogen bonds but also ionic bonds, hydrophobic interactions, and disulfide bonds

--disulfide bonds are very strong covalent bonds between two cysteine residues within the same polypeptide chain that enhance a protein's ability to withstand denaturation

Front 26

Preventing tissue necrosis due to NE extravasation

Back 26

-when norepinephrine is being infused into a vein, blanching of that vein with induration and pallor of tissues surrounding the IV site are signs of NE extravasation and resulting vasoconstriction

-tissue necrosis is best prevented by local injection of an alpha1 blocking drug, such as PHENTOLAMINE

Front 27

Cladribine

Back 27

-cladribine is a purine analog that achieves high intracellular concentrations, because it is resistant to degradation by adenosine deaminase

-cladribine is the drug of choice for hair cell leukemia

-purine analogs that act as anti-metabolites include cladribine (for hairy cell leukoplakia), 6-thiopurines (such as 6-MP, 6-GP), and fludarabine (for CLL)

Front 28

Parietal cell location

Back 28

-parietal cells secrete HCl and intrinsic factor

-primarily found in the superficial (upper) region of the gastric glands

-vs. chief cells – synthesize and secrete pepsinogen, and are primarily found in the deeper region of the gastric glands

Front 29

Omalizumab

Back 29

-omalizumab is an anti-IgE antibody

-omalizumab is effective and acceptable add-on therapy for patients with severe allergic asthma

--shown to reduce dependency on both oral and inhaled steroids

Front 30

Ipatropium

Back 30

-Ipatropium and other anti-muscarin agents can reverse VAGALLY-medidated bronchoconstriction

-vs. methylxanthines like theophylline and aminophylline cause bronchial dilation by decreasing phosphodiesterase enzyme activity, thereby increasing intracellular cAMP

Front 31

Beta-blocker mechanism in thyrotoxicosis

Back 31

-beta-blockers have dual mechanism of action in treating thyrotoxicosis:

--decrease effect of sympathetic adrenergi impulses reaching target organs

--decrease rate of peripheral conversion of T4 to T3

Front 32

GABAa, GABAb, and GABAc receptors

Back 32

-GABAa and c receptors are ion channels, vs. GABAb receptor is linked to a G-protein

-benozodiazepines, barbiturates, and alcohol all bind to different components of the GABAa receptor, thus facilitating GABA's inhibitory action in the CNS

Front 33

Etanercept

Back 33

-etanercept is a tumor necrosis factor-alpha (TNF-alpha) inhibitor added to methotrexate to treat moderate-to-severe rheumatoid arthrisi in patients who have failed methotrexate alone

-etanercept is a fusion protein that links a soluble TNF-alpha receptor to the Fc component of human immunoglobulin G1

-etanercept reduces the biological activity of TNF-alpha by acting as a DECOY RECEPTOR

Front 34

Suffices of biological agents

Back 34

-suffix of a biological agent indicates whether a medication is a monoclonal antibody (mab), a receptor molecule (cept), or a kinase inhibitor (nib)

Front 35

Naloxone

Back 35

-naloxone is a pure opioid receptor antagonist used for treating opioid intoxication or overdose

-although naloxone binds to mu, kappa, and delta opioid receptors, it has greatest affinity for mu receptors, making it an ideal agent for treating opioid intoxication

Front 36

Class IA anti-arrhythmics

Back 36

-class IA anti-arrhythmics are sodium channel-blocking agents that slow phase 0 of the ventricular myocyte action potential

-this action serves to prolong depolarization, as well as the refractory period of these cells

-class IA anti-arrhythmics include quinidine, procainamide, and disopyramide

Front 37

Turner syndrome genetics

Back 37

-mitotic error in early development results in 45,XO (complete monosomy) karyotype.

-this accounts for the majority of cases of Turner syndrome

Front 38

Small-cell lung carcinoma

Back 38

-small cell carcinoma of lung is the most aggressive lung neoplasm

-SCC is though to have a neuroendocrine origin

-tumor cells express NEUROENDOCRINE MARKERS, and contain neuro-secretory granules in the cytoplasm

-i.e., neurofilaments would be present in a small cell carcinoma of the lung

Front 39

Hypertrophic cardiomyopathy

Back 39

-hypertrophic cardiomyopathy often presents as sudden cardiac death in a young athlete

--almost all cases are due to autosomal dominant mutations in cardiac sarcomere proteins

--the most common of protein involved is BETA-MYOSIN HEAVY CHAIN

-vs. about 1/3 of cases of DILATED cardiomyopathy are genetic
--these cases are mostly due to autosomal dominant mutations of cardiac myocyte cytoskeletal proteins (dystrophin) or mitochondrial enzymes

Front 40

Primary myelofiborisis

Back 40

-primary myelofiborsis presents as severe fatigue, splenomegaly (causing early satiety/abdominal discomfort), hepatomegaly, anemia, and BONE MARROW FIBROSIS

-associated with JAK2 mutation

-a JAK2 inhibitor (ruxolitinib) is approved for treatment of primary myelofibrosis

Front 41

Polycythemia vera presentation

Back 41

-polycythemia very presents with pruritus, erythromelalgia, splenomegaly, thrombotic complications, ERYTHROCYTOSIS, and thrombocytosis

-also associated with JAK2 mutation

Front 42

Essential thrombocytosis presentation

Back 42

-essential thrombocytosis presents with hemorrhagic and thrombotic symptoms (easy bruising, microangiopathic occlusion), THROMBOCYTOSIS, and megakaryocytic hyperplasia

-also associated with JAK2 mutation

Front 43

Chronic myelogenous leukemia presentation

Back 43

-CML presents with constitutional symptoms (fatigue, weight loss, sweating), splenomegaly, and LEUKOCYTOSIS WITH MARKED LEFT SHIFT (i.e., mylocytes, metamyelocytes, band forms)

-associated with mutation of Philadelphia chromosome t(9:22) BCR-ABL fusion protein

Front 44

Chronic myeloproliferative disorders (general)

Back 44

-chronic myeloproliferative disorders (polycythemia vera, essential thrombocytosis, primary myelofibrosis) often have a mutation in the cytoplasmic tyrosine kinase, Janus kinase 2 (JAK2)

--this results in constitutive tyrosine kinase activity, with consequent cytokine-independent activation of STAT transcription factors

Front 45

Progressively weakening diaphragmatic contractions

Back 45

-progressively weakening diaphragmatic contractions during maximal voluntary ventilation with intact phrenic nerve stimulation indicate neuromuscular junction pathology (e.g., myasthenia gravis) and/or abnormally rapid diaphragmatic muscle fatigue (e.g., restrictive lung disease, or chest wall disease).

Front 46

Von Willebrand factor

Back 46

-vWF is made by endothelial cells and stored in endothelium and platelets

-vWF binds GP Ib-IX receptors on the platelet membrane and mediates platelet aggregation and adhesion to subendothelial collagen

-vWF also serves as a carrier for factor 8

-deficiency of vWF causes both impaired platelet function and coagulation pathway abnormalities

-the ristocetin aggregation test is used to measure vWF-dependent platelet aggregation

--ristocetin activates GP Ib-IX receptors on platelets and makes them available for vWF binding

--when the vWF level is DECREASED, there is poor platelet aggregation in the presence of ristocetin

-since vWF serves as carrier for factor 8 (and prolongs its half-life), low vWF causes prolonged bleeding after minor surgeries, and PROLONGED PTT

Front 47

Glanzmann thrombasthenia

Back 47

-hereditary deficiency of GP IIb-IIIa receptors

--> mucocutaneous bleeding and increased bleeding time

-platelet aggregation is decreased with addition of ADP

Front 48

Thromboxane A2 deficiency

Back 48

-deficiency of thromboxane A2 is associated with aspirin treatment, due to irreversible inactivation of COX in platelets

--> decreased platelet adhesion and aggregation

Front 49

Congenital deficiency of Hageman factor

Back 49

-congenital deficiency of factor 12 (Hageman) does not cause symptoms

-usually incidental finding because it causes PTT prolongation

Front 50

Risk

Back 50

-risk is probability of getting a disease over a certain period of time

-to calculate risk, divide number of diseased subjects by total number of subjects in the corresponding group (i.e., all of the people at risk).

Front 51

Opioid withdrawal

Back 51

-opioid withdrawal is marked by abdominal pain, nausea, vomiting, diarrhea, piloerection, lacrimation, and diaphoresis

-yawning, dilated pupils, lacrimation, hyperactive bowel sounds seen on physical exam

-can occur after cessation or very reduced use of narcotics

-opioid withdrawal is generally not life-threatening, and does not result in seizures like withdrawal from alcohol and benzodiazepines.

Front 52

Alcohol withdrawal

Back 52

-symptoms of alcohol withdrawal: tremors, agitation, anxiety, delirium, psychosis

-findings: seizures, tachycardia, palpitations

Front 53

Benzodiazepine withdrawal

Back 53

-benzo withdrawal: tremors, anxiety, perceptual disturbances, psychosis, insomnia

-same findings as alcohol withdrawal: seizures, tachycardia, palpitations

Front 54

Withdrawal from stimulants

Back 54

-withdrawal from stimulants (cocaine, amphetamines): increased appetite, hypersomnia, intense psychomotor retardation, severe depression ("crash")

-no significant physical findings

Front 55

Nicotine withdrawal

Back 55

-nicotine withdrawal: dysphoria, irritability, anxiety, increased appetite

-no significant physical findings

Front 56

Granulomatosis with polyangiitis (Wegener's)

Back 56

-granulomatosis with polyangiitis is a cause of rapidly progressive (crescentic) glomerulonephritis (RPGN) type 3 (pauci-immune)

-symptoms of nephritis are accompanied by signs of upper and lower respiratory tract involvement

-crescents on light microscopy, absence of deposits on immunofluorescence, and elevated serum c-ANCA are diagnostic.

-but immunofluoresence will show reaction to neutrophils

Front 57

Granulomatous inflammation

Back 57

-foreign bodies (e.g., retained sutures) can elicit a granulomatous response, which can present as tender erythematous brown/purple papule, nodule, or plaque

-granulomatous inflammation is a form of chronic inflammation, characterized by aggregates of activated macrophages that assume an epithelioid appearance

-persistent grnulomatous inflammation with subsequent fibrosis can cause organ dysfunction, which is seen in various granulomatous diseases

Front 58

Granulomatous inflammation

Back 58

-microscopically, granulomas characterized by aggregates of activated macrophages that assume an epithleioid appearance

-often surrounded by rim of lymphocytes that synthesize cytokines responsible for continued macrophage activation

-multi-nucleated giant ells, derived from fusion of several macrophages, may also be found in granulomas

-granulomas associated with certain infection organisms (TB) can develop a central zone of necrosis due to hypoxia and free-radical injury
--this appears grossly as a granular and cheesy (caseating) necrosis

Front 59

Granuloma formation

Back 59

-granuloma formation is a complex process that occurs over several days to weeks in response to an antigen that can't be eradicated by the usual immune mechanisms

-activated Th1 CD4+ cells secrete interferon-gamma, which activates macrophages

-macrophages then secrete TNF-alpha, which results in further macrophage maturation and formation of the granuloma

-the granuloma serves to wall off the offending agent

-but agent is not always eradicated, as certain pathogens (TB) are resistant to killing

-persistent granulomatous inflammation with subsequent fibrosis can cause organ dysfunction.

Front 60

Anemia in women of child-bearing age

Back 60

-anemia in women of childbearing age is usually caused by iron deficiency, secondary to menstrual blood loss.

-may present with conjunctival pallor and fatigue

-leads to:

-decreased bone marrow iron stores (ferritin and hemosiderin)
-decreased serum ferritin
-increased serum total iron binding capacity, reflecting increased serum transferrin
-decreased serum iron concentration
-decreased blood hemoglobin
-appearance of MICROCYTIC, HYPO-CHROMIC RBCs