Uworld - 46 Q's

Front 1

Elastase in the lungs

Back 1

-elastase is a neutral protease found in macrophage lysosomes, and in the large azurophil (primary) granules of neutrophils.

-normally, elastase release from infiltrating neutrophils and macrophages is balanced by the anti-elastase activity of serum alpha1 anti-trypsin.

-excess elastase activity in the lung acini thought to be major factor in development of centriacinar and panacinar emphysema

Front 2

Type I pneumocytes

Back 2

-comprise 95% of epithelial lining of lung

-end-differentiated squamous cells

Front 3

Type II pneumocytes

Back 3

-type II pneumocytes secrete phospholipid species, including dipalmitoyl phosphatidlycholine (major components of pulmonary surfactant)

Front 4

Clara cells

Back 4

-Clara cells = non-ciliated secretory cells of the terminal respiratory epithelium

-secrete clara cell secretory protein (CCSP), which inhibits neutrophil recruitment and activation

Front 5

Ophthalmopathy in Grave's Disease

Back 5

-Patient's with Graves disease can have extra-thyroid manifestations, such as infiltrative ophthalmopathy and pretibila myxedema (derm complication due to hypothyroidism)

-infiltrative ophthalmopathy characterized by edema and infiltration of lymphocytes into extra ocular muscles and connective tissue --> inflammation

-high-dose glucocorticoids (e.g., prednisone) used to control severe Graves ophthalmopathy

--helpful in decreasing severity of inflammation and decreasing extra-ocular volume

--vs. conventional anti-thyroid drugs, which are not anti-inflammatory and therefore do not alter the ophthalmopathy

Front 6

Cystic fibrosis inheritance

Back 6

CF is an autosomal recessive disease – defective cystic fibrosis transmembrane conductance regulatory (CFTR) gene on chromosome 7

-Probability that an autosomal recessive disease will be transmitted to a child can be calculated based on mom and dad's pedigrees

-an unaffected individual with unaffected parents who has a sibling affected by an AR condition has a 2/3 chance of being a carrier for that condition.
--because she is not homozygous recessive – so she has to be either homozygous dominant (1/3 chance) or heterozygous (2/3 chance, because mom and dad are both carriers).

Front 7

-Auer rods

Back 7

-presence of rod-shaped intracytoplasmic inclusions (Auer rods) is characteristic of many forms of acute myeloblastic leukemia (AML)

-The M3 variant of AML is acute pro-myelocytic leukemia – shows many Auer rods – associated with the cytogenetic abnormality t(15:17)

Front 8

Number needed to harm

Back 8

NNH = 1/attributable risk

-to determine attributable risk, first calculate adverse event rates in the treatment and placebo groups
--this is equal to adverse events (e.g., deaths) over total subjects in this group

-attributable risk difference is equal to overall attributable risk.

-1/attributable risk = number needed to harm

vs. number needed to treat = 1/absolute risk reduction

Front 9

Fabry disease

Back 9

-inherited deficiency of alpha-galactosidase A

-causes accumulation of the globoside ceramide trihexoside in tissues

--presentation: "sample of fibroblast cultured from patients skin lesions fibroblasts fail to metabolize ceramide trihexoside."
-earliest manifestations are angiokeratomas, hypohidrosis, and acroparesthesia

-without enzyme replacement, patients typically develop PROGRESSIVE RENAL FAILURE

Front 10

Schizoaffective disorder

Back 10

-Schizoaffective disorder is characterized by symptoms of schizophrenia in presence of prominent mood symptoms

-period of at least 2 weeks of psychotic symptoms in absence of mood symptoms required for diagnosis

--sample presentation: mood fluctuation with inappropriate sexual advances, wacko statements (ex-girlfriend communicating with him telepathically), with symptoms for last month.

Front 11

Selective COX-2 inhibitors (Celecoxib) and platelet aggregation

Back 11

-Selective COX 2 inhibitors have potent anti-inflammatory effects, WITHOUT the side effects of bleeding and GI ulceration associated with non-selective COX inhibitors.

-selective COX 2 inhibitors do not impair platelet function, because platelet mostly express COX 1

Front 12

Acute epiglottitis

Back 12

-acute epiglottitis is a rapidly progressive infection of epiglottis – leads to severe inflammation and edema of epiglottis and larynx, with potentially acute obstruction of airway, especially during laryngoscopy.

-presentation: rapidly progressing fevere, severe sore throat, drooling, progressive airway obstruction (with stridor)

-this illness is most often caused by H. influenza type b, but the Hib vaccine has dropped incidence of this disease considerably.

--However, H. influenza type b can still cause disease in unimmunized or improperly immunized patients (and occasionally in fully immunized patients)

Front 13

Host defense against mycobacterial infections

Back 13

-defense against mycobacterial infections depends on interactions between macrophages and T cells.

-interferon gamma, a pleoitropic Th1 cytokine, is a key factor in elimination of these infections.

--macrophages infected with mycobacteria produce interleukin 12 --> stimulates T cells and natural killer cells to produce IFN-gamma

--IFN-gamma then binds to its receptor, leading to receptor dimerization and activation of Janus kinases 1 and 2.

--this results in nuclear signaling, via STAT1 and transcription of IFN-gamma-related genes, which promote mycobacterial killing by phagocytes.

-IFN-gamma also enhances viral and parasitic resistance, by increasing expression of MHC and intrinsic disease factors

Front 14

Deficiencies in IFN-gamma receptors (AR)

Back 14

-autosomal recessive deficiencies in IFN-gamma receptor (or other pathway elements) result in disseminated mycobacterial disease in infancy or early childhood, including disseminated infection by the BCG vaccine strain (for TB) if administered.

-once identified, patients require lifelong treatment with continuous anti-mycobacterial antibiotics

Front 15

Right heart failure without clinically apparent edema

Back 15

-right heart failure increases central venous pressure (CVP), which leads to a rise in capillary hydrostatic pressure, net plasma filtration, and interstitial fluid pressure.

-as interstitial fluid pressure increases, so does lymphatic drainage, which can COMPENSATE FOR MODERATE ELEVATIONS IN CVP and prevent development of clinically apparent edema

-however, large CVP elevations can overwhelm lymphatic reabsorptive capacity, leading to development of overt edema.

Front 16

Acute vs. chronic mitral regurgitation

Back 16

-patients with acute mitral regurg have near-normal left atrial (LA) compliance.
--so they tend to develop marked pulmonary hypertension and pulmonary edema (due to back flow)

-vs. patients with chronic mitral regurgitation acquire adaptive increase in left atrial volume and compliance
--they are therefore less prone to pulmonary hypertension and edema (won't develop acute pulmonary edema), but they are more prone to atrial fibrillation and mural thromboembolism

Front 17

Pulmonary hypertension due to reactive vasoconstriction in the lungs

Back 17

-left ventricular dysfunction can lead to increased pulmonary arterial pressure due to reactive vasoconstriction (secondary to pulmonary venous congestion)

-mech: rise in hydrostatic pressures causes capillary leak and subsequent pulmonary edema
--this edema causes alveolar collapse and results in decreased ventilation, which in turn causes hypoxemia
--reactive vasoconstriction occurs to shunt blood toward areas where ventilation is less compromised

--this results in pulmonary arterial hypertension, with resultant increase in after load (which causes right-sided heart failure).

-reactive changes in the pulmonary vasculature (e.g., endothelial dysfunction causing further vasoconstriction) also contribute to pulmonary hypertension

Front 18

Lunate bone

Back 18

-can be identified on hand x-ray as the more medial of the two carpal bones that articulate with the radius.

-lunate lies immediately medial to the scaphoid bone

"So Long To Pinky, Here Comes The Thumb"

Scaphoid, lunate, triquetrium, pisiform
hamate, capate, trapezoid, trapezium

Front 19

Deep brachial artery and radial nerve

Back 19

-when midshaft of humerus is fractured, there is significant risk or injury to the radial nerve and deep brachial artery (these run together!).

-radial nerve innervates most of the forearm extensors at elbow, and most of hand extensors at the wrist.

--"that was a RAD X-games, bro"

-radial nerve also innervates extrinsic extensors of the digits (the brachioradialis and supinator muscles), and provides cutaneous sensory innervation to dorsal (back of) hand, forearm, and upper arm.

-along with midshaft fractures of the humerus, supracodylar fractures (above elbow) are also associated with injury to brachial artery

Front 20

Ulnar nerve injury

Back 20

-ulnar nerve injury classically causes a "claw hand" deformity

-ulnar nerve can be injured either near the medial epicodyle of the humerus, or in Guyon's canal near the HOOK OF THE HAMATE and pisiform bone in the wrist

-"U battled Hook in Guyon's canal"

Front 21

FSH in menopause

Back 21

-Elevated serum FSH level confirms menopause – can be used if diagnosis is uncertain

-although LH level will also be elevated, this is a later and les spromient phenomenon

-menopause is normal event of aging – caused by age-related exhaustion of ovarian follicles

-estrogen production in post-menopausal females drops significantly as ovaries becomes less active.
-Follicle-stimulating hormone (FSH) levels then increase because of loss of inhibition of estrogen feedback*

-absence of menstrual cycles for 6 months with associated hypo-estrogenic symptoms (hot flashes, atrophic vaginitis) is highly suggestive of menopause.
-measuring serum FSH is reliable way to confirm
--generally FSH levels will be higher than 30 U/L

--while LH levels also rise, this occurs later in menopause, making it a less sensitive test than FSH

Front 22

Cross-sectional study

Back 22

-in a cross-sectional study, exposure and outcome are measured simultaneously at a certain point of time ("snapshot study")

-vs. other study designs in which a certain time period separates exposure from outcomes measured

Front 23

Tryptase in anaphylaxis

Back 23

-anaphylaxis is due to widespread mast cell degranulation

-although histamine is the major effector of anaphylaxis, tryptase is also released in excess
--since tryptase is an enzyme relatively specific to mast cells, it is often used as a marker of mast cell activation.

Front 24

Mast cell degranulation (mechanism)

Back 24

-degranulation of mast cells is accomplished by cross-linking of multiple membrane-bound IgE antibodies by a specific antigen.

-this results in IgE-Fc receptor aggregation on the mast cell surface, with subsequent degranulation

Front 25

alpha-ketoglutarate dehydrogenase

Back 25

-Krebs enzyme
-converts alpha-ketoglutarate to succinyl CoA, and forming one NADH

-requires "Tender Loving Care For Nancy"
-Thiamine, Lipoic acid, CoA, FAD, NAD+

-Since alpha-ketoglutarate dehydrogenase requires thiamine as a cofactor, giving glucose to thiamine-deficient patients (e.g., alcoholics), will result in Wenicke encephalopathy

--Wernicke encephalopathy occurs due to increased thiamine demand
--present with acute confusion, opthalmoplegia (intra-ocular muscle weakness), and ataxia

Front 26

Rheumatoid factor

Back 26

-RA is an autoimmune disease triggered by an unknown antigen

-cartilage components serve as auto-antigens, activating CD4+ T-cells, which in turn stimulate B-cells to secrete rheumatoid factor.

-rheumatoid factor is an IgM antibody specific to the Fc component of self IgG

Front 27

Oranophophate poisoning

Back 27

-exposure to certain insecticides can causes organophosphate poisoning

-resultant CHOLINESTERASE INHIBITION is long and profound because organophosphates bind IRREVERSIBLY to cholinesterase

-this causes a state of cholinergic excess, marked by excessive salivation, lacrimation, diaphoresis, urinary incontinence, diarrhea, emesis, miosis, and bradycardia

-DUMBELSS

-defecation, urination, miosis (tiny pupils), bradycardia, emesis, lacrimation, salivation, sweating

Front 28

Atropine

Back 28

-atropine is an anti-cholinergic agent

-used pharmacologically to block post-junctional acetylcholine receptors

-atropine is the antidote for organophosphate poisoning.

-atropine toxicity causes symptoms that are opposite cholinergic effects (constipation, midriasis, dry mouth, etc.)

Front 29

Hepatic steatosis

Back 29

-hepatic steatosis is nonspecific condition, characterized by triglyceride accumulation within the hepatocellular cytoplasm

-pathogenesis of alcohol-induced hepatic steatosis appears related mostly to DECREASE IN FREE FATTY ACID OXIDATION,

--occurs secondary to excess NADH production by the two major alcohol metabolism enzymes (alcohol dehydrogenase, and aldehyde dehydrogenase)

-contributing pathogenetic factors include impaired lipoprotein assembly and secretion, and an increase in peripheral fat breakdown.

-fatty tissue will microscopically demonstrate cytoplasmic vacuoles as the lipid is dissolved during histologic processing.

-in frozen sections, lipids can be demonstrated by staining with oil red O or Sudan black

Front 30

Lecithinase (alpha toxin)

Back 30

-lecithinase (alpha toxin) is the main toxin produced by C. perfringens

-function is to degrade lecithin, a component of cellular phospholipid membranes --> membrane destruction, cell death, and widespread necrosis/hemolysis.

Front 31

Breast cancer drugs

Back 31

-Anastrozole: selective inhibitor of aromatase (enzyme that converts androgens to estrogens)

-Ketoconazole:
--antifungal agent that decreases androgen synthesis by inhibiting multiple enzyme pathways involved in synthesis of androgens

-Trastuzumab
--inhibits epidermal growth factor and HER2/neu pathways --> apoptosis of breast cancer cells

-vs. activation of the HER2/neu receptor – causes activation of tyrosine kinase

Front 32

Bacillus anthracis virulence factors

Back 32

-two main virulence factors of Bacillus anthraces

--anti-phagocytic poly-y-D-glutamic acid capsule

--anthrax exotoxin – timeric toxin composed of protective antigen EDEMA FACTOR, and lethal factor

-Bacillus anthracis edema factor is an edentate cyclase that causes massive increases in intracellular cAMP --> neutrophil and macrophage dysfunction with tissue edema

-this mechanism of action is simlar to that of adenylate cyclase toxin, produced by Bordetella pertussis

Front 33

Diagnosing infection of Treponema pallidum (syphilis)

Back 33

-common means of diagnosing infection with Treponema palladium involves screening and confirmatory tests.

-screening tests are known as RPR and VDRL, and confirmatory test is known as the FTA-ABS, which detects for antibodies against Treponema (a spirochete)

Front 34

Listeria monocytogenes

Back 34

-Listeria monocytogenes = gram positive rod that produces a very narrow zone of beta-hemolysis on blood agar
--shows tumbling motility
--can be cultured at low temperatures (allows bacteria to contaminated refrigerated food)

-INTACT CELL MEDIATED IMMUNITY IS ESSENTIAL FOR ELIMINATION of this bacterium from the body
--"virus, fungus, listerius"

--neonates up to 3 months of age are especially vulnerable, as their cell-mediated immunity is not yet fully developed.
--also susceptible are immunocompromised, elderly, and pregnant patients

Front 35

Eosinophil action

Back 35

-important for eradicating parasitizing infections (e.g., helminths) from body

Front 36

Deficient humoral immunity

Back 36

-patients with pure humoral immune defects (e.g., X-linked agammaglobulinemia of Bruton) are at increased risk of bacterial infections by Streptococci and Staphylococci

--but have normal responses to infections combated by cell-mediated immunity (Listeria, viruses, fungi)

Front 37

Mast cell functions

Back 37

-mast cells contribute to defense against parasites

-also importnat in allergic responses, esp. hypersensitivity reactions

-mast cells don't confer immunity to intracellular pathogens

Front 38

Complement deficiencies

Back 38

-Patients with inherited deficiencies of terminal complement components (C5b-C9) are unable to form the membrane attack complex (MAC) and are predisposed to recurrent NEISSERIA infections

"I would complement you on that nice infection, but I can't"

Front 39

Pick's disease

Back 39

-rare cause of dementia

-characterized by destruction of frontal lobes (i.e., frontal cortex)

-behavioral abnormalities seen – apathy, socially inappropriate behavior

-manifests with progressive dementia, behavioral disinhibition, and speech difficulties, including dysarthria (problems with muscles that control speech), aphasia (language problems), echolalia (automatic repetition of words)

Front 40

Diazepam

Back 40

-long-acting benzodiazepine

-used as anxiolytic (anxiety drug)
--sedative
--anticonvulsant
--muscle relaxant (can stop spasticity caused by upper motor neuron disorders MS, strokes, spinal cord trauma, as well as tetanus)

-Chlorpheniramine – first-generation anti-histamine that causes sedation – should NOT be used with diazepam.

Front 41

Pyelonephritis dx

Back 41

-WBC casts are formed in tubules – PATHOGNOMONIC for acute pyelonephritis when accompanied by systemic manifestations of febrile illness.

-WBC casts also seen with acute interstitial nephritis, but clinical presentation is different, as patients have only low-grade fever and do not experience painful urination.

-vs. pyuria and bacteruria – non-specific, and found in both upper and lower UTIs

Front 42

6-mercaptopurine degradation

Back 42

-6-mercaptopurine is mainly degraded in liver by xanthine oxidase

-allopurinol (an inhibitor of xanthine oxidase) can increase concentration of 6-mercaptopurine significantly

-both 6-mercaptopurine and 6-thioguanine are pro-drugs that require activation by HGPRT

Front 43

Malabsorption workup

Back 43

-malabsorption = syndrome of impaired intestinal digestion and absorption

-Sudan III stain of stool identifies fecal fat – used to screen for malabsorption

-stool sample is appropriate next step in patient with symptoms of malabsoprtion

Front 44

Sodium valproate – use

Back 44

-sodium valproate (or just valproate) is drug of choice for patients with absence seizures and associated tonic-clonic seizures

-ethosuximide is also effective against absence seizures, but does not suppress tonic-clonic seizures

Front 45

Verapamil – axn and side effects

Back 45

-Verapamil is a calcium channel blocker

-has most effect on heart – nifedipine is most selective for peripheral vasculature – diltiazem has intermediate effect

-most frequent adverse reactions seen with verapamil are constipation and gingival hyperplasia
-also seen are bradycardia, and AV nodal block (1-2% of patients)

Front 46

Burkitt lymphoma dx

-presentation: African immigrant with rapidly enlarging jaw mass
-mass biopsy shows numerous mitotic figures and apoptotic bodies

Back 46

-histo: Burkitt lymphoma has a "starry sky" appearance due to presence of macrophages and apoptotic bodies in a "sea" of medium-sized lymphocytes

-rates of mitts and apoptosis in the cancerous tissue are high

-almost all cases of Burkitt lymphoma are associated with TRANSLOCATIONS OF THE C-MYC GENE on chromosome 8, usually onto the Ig heavy chain region of chromosome 14 – t(8:14)

Front 47

Polycythemia vera

Back 47

-clonal myeloproliferative disease of pluripotent hematopoietic stem cells

-characteristic features: increased RBC mass, increased plasma volume, and LOW erythropoietin levels

-most patients with polycythemia vera have the JAK2 V617F mutation --> hematopoietic stem cells more sensitive to growth factors

-only red cells are increased, so a better term for the disease is "secondary erythrocytosis"

Front 48

Cholelithiasis in women who are pregnant or using oral contraceptives

Back 48

-estrogen-induced cholesterol hypersecretion and progesterone-induced gallbladder bypomotility are responsible for increased incidence of chilelithiasis in women who are pregnant of using oral contraceptives

Front 49

Bullous pemphigoid

Back 49

-bullous pemphigoid is characterized by auto-antibodies to the HEMIDESMOSOMES along the basement membrane of the dermal-epidermal junction

Front 50

Gibbs free energy

Back 50

-if free energy of products of a reaction is lower than that of the substrates, the sign of "change in G" will be negative
--this indicates that the reaction FAVORS PRODUCT FORMATION

-if free energy of the products is higher than that of the substrates, change in G will be positive --> reaction favors substrate (not product) formation

Front 51

Dietary fructose metabolism

Back 51

-dietary fructose is phosphorylated in the liver to F-1-P, then rapidly metabolized because it bypasses PFK-1, the rate-limiting enzyme of glycolysis

-other sugars enter glycolysis BEFORE this rate-limiting step --> metabolized more slowly than fructose due to regulation by PFK-1.

Front 52

Gallstones

Back 52

-brown pigment stones typically arise secondary to infection of biliary tract, which results in release of BETA-GLUCURONIDASE by injured hepatocytes and bacteria

-presence of beta-glucouronidase enzyme contributes to hydrolysis of bilirubin glucuronides, thus increasing the amount of unconjugated bilirubin in bile, and predisposing to bilirubin stones.

Front 53

High altitude exposure

Back 53

-high altitude exposure that lasts more than a few days will result in hypoxemia, with chronic respiratory alkalosis

-corresponding decrease in serum bicarbonate levels is reflective of renal compensation

-sample values: PaO2 = 60 mmHg, PaCO2 = 20 mmHg, Plasma HCO3- = 15 mEq/L