UWorld SA 1 Flashcards
What potentially serious complication (aside from fractures) is paget’s disease of the bone frequently associated with? How would this condition appear?
Osteosarcoma -> Persistent pain (in hip if femur etc.) that does not improve with NSAIDs.
Imaging: area w/ mixed lysis and sclerosis, w/ focal periosteal elevation and reactive new bone formation. Ossification of adjacent soft tissue in “sun-burst” pattern
What genetic consequence should be considered if a particular disease occurs in the offspring but is not apparent in the parents and negative family history?
Germline mosaicism
What is penetrance?
The extent of phenotypical expression of a mutated gene.
e.g. incomplete penetrance only sometimes produces symptoms in those w/ mutation
What is one of the most important prophylactic care-taking measures in diabetic patients (aside from blood sugar control)?
Daily foot inspection
What is the most common translocation in childhood B-cell ALL?
t(12;21)
What disorder consists of immature myeloid cells on blood smear, containing Auer Rods?
AML or subtype APL t(15;17)
What does a blood smear in CML look like?
numerous immature leukocytes with large basophilic nuclei and ground glass appearance of cytoplasm
Which cytokine is produced exclusively by lymphocytes? What effect does this have?
IL2 -> only by antigen stimulated T cells -> stimulates growth and differentiation of T cells, B cells, NK cells and macrophages
Which cells generate interferon-alpha (IFN-alpha)? What is the purpose of this compound?
Monocytes, macrophages, B cells, NK cells -> numerous antiviral functions -> viral replication inhibition, protection of uninfected cells from infection, stimulation of lymphocyte and NK cell cytotoxicity
A patient is injured in a sports accident that causes gross posterior displacement of the tibia relative to the femur, what is most likely injured?
Popliteal fossa traction -> damage to politeal artery
Tibial nerve is not subject to same level of traction forces, more likely to be destroyed in penetrating injury
A patient presents following giving birth with fever, uterine tenderness, foul smelling discharge and leukocytosis. What is the most likely causative agent?
Endometritis -> infection of endometrium -> bacteroides species most commonly isolated
What is the most common location for bicarbonate excretion in the digestive tract and how is this release stimulated?
S endocrine cells of duodenal mucosa release SECRETIN in response to increased duodenal acid -> stimulates bicarb release from exocrine pancreas and epithelial cells of biliary tract (bicarb, Cl- antiporter is responsible for this)
How do you differentiate acute stress disorder from PTSD?
They have similar symptoms and acute stress disorder becomes PTSD when symptoms persist for > 4 weeks
A probe is measuring blood flow towards the cardiac apex and detects a large peak of flow towards the probe. What does this represent and what sound would be heard here?
Diastolic filling of the heart -> could hear 3rd heart sound in patients with ventricular failure
A patient presents following an automobile accident with a chest XRay demonstrating diffuse, fluffy alveolar infilitrates. What is happening and what is the cause of this?
ARDS -> injury to endothelial cells lining pulmonary capillaries adjacent to the alveoli
What is pseudobulbar paresis?
Caused by conditions like MS -> dysarthria, dysphagia, dysphonia and impaired movement of tongue and facial muscles
What is the MoA of phentolamine? Pralidoxime?
Phen - competitive blockage of alpha-Receptors (good for excess Epi/NE)
Pral - Antidote to organophosphates -> it reactivates phosphorylated cholinesterases by removing phosphate groups (note: this drug only fxns if NMJ has been affected by organophosphate anticholinesterases)
What is methylphenidate? What would occur from drug toxicity?
Piperidine-derived medication -> stimulates cerebral cortex in a similar manner to amphetamines
Toxicity -> confusion, dry-mucous membranes, and mydriasis
Which cell receptors function by translocation to the nucleus?
Ligands binding cytoplasmic steroid, thyroxine or retinoid receptors
What enzyme deficiency leads to the most common type of porphyria?
Porphyria Cutanea Tarda (PCT, photosensitivity) is caused by a deficiency in URO decarboxylase which converts Uroporphyrinogen III -> Coproporphyrinogen III
How can you distinguish the symptoms of myasthenia gravis vs. Eaten Lambert syndrome?
MG -> associated w/ thymic mass (thymoma) and more weakness in facial, periocular, bulbar (mouth weakness) and pelvic gridle muscles.
E-LS -> associated w/ lung small cell carcinoma is much less common and presents w/ extremity weakness
What are the signs and features of complete androgen insensitivity syndrome?
X-linked disorder causing mutated testosterone receptors all over body -> resistant to androgens
46 XY male w/ a female phenotype (breasts, hairless, no penis/scrotum, & vagina ending in blind pouch -> NO uterus, fallopian tubes, or upper vagina), cryptorchid testes in abdomen, inguinal canal or labia majora
Which drug can provide long term relief for excess catecholamine surge (as w/ pheochromocytoma)? Short term?
Phenoxybenzamine has a very long half life (1 day) and can provide relief of symptoms for a few days.
Prazosin -> half life of 3 hours, relief for 1 day
Phentolamine half life is 20 minutes -> short relief
A patient being treated for ventricular arrythmias presents w/ dyspnea, cough, chest pain. PE revelas bilateral inspiratory crackles and CXR reveals patchy areas of interstitial inflammation. What is most likely the cause of this?
Amiodarone -> can cause inflammation and fibrosis of pulmonary interstitium and can become chronic condition of interstitial pneumonitis (slow progressing dyspnea and nonproductive cough)
What are the main side effects of Sotalol? Diltiazem?
Sot -> Torsade de pointes, excess beta blockade (bradycardia and hypotension)
Diltiazem -> Bradycardia, decreased myocardial contractility, flushing, hypotension, GI disturbances
What process is responsible for anchoring plasma membrane spanning proteins (like G-prot) to the inner cytoplasmic membrane?
Palmitoylation -> links fatty acids covalently to cysteine residues -> many G-prot coupled receptors have carboxyl tails palmitoylated on cystein residues
What is variable expressivity?
variations in phenotypic severity of a disease between individuals with the same exact gene mutation
What is allelic heterogeneity? Give an example of this.
Different mutations in same gene locus cause similar phenotypes.
e.g. Duchenne Muscular dystrophy has mutation in dystrophin gene causing complete loss of fxn, while Becker MD has dystrophin mutation that results in structurally abnormal but partially functioning dystrophin gene produc
What are the features of hemochromatosis and at what age do patients with this condition usually present?
40s (when about 20 grams of iron have accumulated) -> Liver disease (hepatomegaly), Dermal hemosiderin deposits (skin hyperpigmentation, “strange tan”), Pancreatic islet cell destruction (diabetes), Impotence and cardiac dysfunction
Which bacteria can cause impetigo?
Group A strep (pyogenes) and Staph Aureus
What mutation leads to Bruton agammaglobulinemia and which chromosome is involved? What are characteristic features of this disease?
X-linked agammaglobulinemia from mutation in Bruton’s tyrosine kinase which is normally activated in CD19+ B-cells allowing for maturation -> w/ deficiency B-cells cant mature and leave bone marrow
Sx: recurrent bacterial infections of respiratory tract
What enzyme is deficient in maple syrup urine disease and what is an important cofactor of this enzyme?
defect in branched-chain alpha-keto acid dehydrogenase complex which requires thiamine pyrophosphate (V. B1) as a coenzyme (also necessary for transketolase fxn)
What reactions require pyridoxine (V. B6) to function?
Transamination (ALT, AST), decarboxylation, glycogen phosphorylase and often for synthesis of many neurotransmitters, cystathionine, heme, niacin, and histamine
A patient w/ pheochromocytoma produces many catecholamines. Which biochemical compounds in this production pathway require methylation?
NE -> Epinephrine and Epi -> Vanillylmandelic Acid
DOPA -> dop is decarboxylation and Dop -> NE is hydroxylation
Which antibacterial drug will induce an increase of blood histamine concentration as the rate of drug infusion increases? What are major SEs of this drug?
Vancomycin -> can cause severe pruritis and rash upon infusion (Red man syndrome) via nonspecific wide spread histamine release (NOT IgE mediated thus reducing infusion will improve symptoms)
What is the most common reaction to penicillin and other beta-lactam drugs?
IgE-mediated hypersensitivity reaction (not related to histamine release) -> thus reducing drug dose/infusion will not decrease histamine release immediately
What is Albright Hereditary osteodystrophy?
Skeletal and developmental defects (short stature, short metacarpal/metatarsal bones) and end organ resistance to PTH, TSH, and LH/FSH
What maintains testosterone concentrations in the seminiferous tubules?
Androgen-Binding Protein (ABP) released by sertoli cells -> ensures high levels of testosterone to facilitate proper maturation of sperm
If a patient presents after fasting with signs of starvation and is hypoglycemic w/ low ketones, what should that indicate? What about if there is high ketone levels?
Defect in either beta oxidation or ketone body synthesis. if beta oxidation -> usually defect in acyl-CoA dehydrogenase (most common is the one that degrades medium chain fatty acids)
Hyperketosis -> indicates glycogen storage disease (glycogen phosphorylase
What factors can alter the velocity (and Vmax) of enzymatic reactions?
Concentration of enzyme, substrates, and/or product (higher concentrations of enzyme/substrate and lower product = higher velocities)
What are the effects of a competitive inhibitor on the Lineweaver Burke plot?
A competitive inhibitor will increase Km -> shifting x intercept to the right
What is the sensitivity of chlamydia to penicillins?
Lacks peptidoglycan cell wall -> INSENSITIVE to penicillins
Instead they have Cysteine-rich outer membrane protein membranes w/ S-S bridges
What is the pathological process that can lead to vertebral fractures in those w/ Vit. D deficiency (e.g. in a patient w/ poor diet)?
Low V. D -> Secondary Hyperparathyroidism (PTH increase) -> Decreased bone mineralization and deposition of unmineralized OSTEOID matrix around normally mineralized trabeculae -> these newly formed Osteoid deposits are weak and prone to fracture
What are the papovaviruses?
DNA viruses that include papillomaviruses and polyomaviruses -> small non enveloped w/ circular doublestranded DNA -> cause disease by infecting and replicating in the NUCLEUS of human EPITHELIAL cells using HOST enzymes -> prone to cancer formation
What is unique about the poxvirus family?
Largest viruses w/ a linear, doublestranded DNA genome -> unique among DNA viruses b/c genome replication occurs completely in the cytosol using many viral encoded enzymes
Which areas are coccidiodes immitis endemic and what lung lesions will it cause?
Southwest US, Texas and also parts of Mexico and South America
Forms thin-walled cavitary lesions -> blood streaked sputum and skin rash on arms
What is unique about autonomic postganglionic nerves?
Unmyelinated axons (preganglionic autonomic, tendon sensory, pacinian corpuscles are myelinated)
How are antigens bound by MHC class II molecules processed?
Invariant chain brings alpha and beta chains together during processing on the RER -> this travels through the Golgi -> goes to endocytic compartment -> invariant chain is cleaved and external protein inserted between a and b chains
What is elevated baseline insulin levels highly suggestive of?
Insulin resistance (insulinoma would have fasting hypoglycemia)
How does itraconazole function?
Inhibits 14-alpha-sterol demethylase impairing lipid (ergosterol) formation -> upstream products accumulate -> impair membrane function
Which organisms have peptidoglycan cell walls?
BACTERIA (NOT fungi)
What is lichen sclerosis et atrophicus (LS&E) and how will a patient present?
Inflammatory condition w/ antibodies against ECM1 protein
- Sx = pruritis, dysuria, pain w/ pooping, and dyspareunia
- PE = rash commonly on female genital/perianal region w/ white patches of thinned skin which can come to involve entire region -> could become genital squamous cell CA
What surfaces can develop leukoplakia?
Mucosal surfaces mouse or inside genitals
Which regions are principally affected in ischemic acute tubular necrosis (ATN)?
Cellular necrosis is limited to outer medullary regions b/c renal medulla is particularly susceptible to ischemic injury b/c of lower blood flow
Biopsy -> detachment of tubules from basement membranes, and occlusion of tubules by casts from damaged epithelial cells and proteins (glomeruli are typically normal)
Which conditions can lead to cortical necrosis of the kidneys?
In rare conditions severe sepsis will cause this -> glomerular necrosis and thrombosis would be seen
Which conditions form alveolar hyaline membranes?
ARDS and hyaline membrane disease of neonates (not associated w/ pulmonary HTN)
What effect would pernicious anemia have on digestive compounds?
Damage of gastric mucosa -> Hypochlorhydia -> increased Gastrin levels
What is the purpose of COX2?
Enzyme formed in response to inflammatory stimuli (not within platelets) and forms prostacyclin (PGI2) which inhibits platelet aggregation and causes vasodilation.
Note: Selective Cox 2 may promote platelet aggregation because of this
What will form in the renal tubules w/ ethylene glycol poisoning?
Glycolate metabolizes into oxalate -> risk of calcium oxalate stone formation
What is Prader-Willi syndrome?
Loss of paternally inherited genes on chromosome 15 or maternal uniparental disomy -> Neonatal hypotonia, Hyperphagia/obesity, Hypogonadism, Dysmorphic facies, Intellectual disability
What can FISH be used to identify?
Detection of sequences as small as 100 kbs -> can be used to identify microdeleions (e.g. 15q11-13 region in Prader Willi or Angelman syndrome)
What forms a callus?
Thickening of stratum corneum (highest layers of epidermis)
What hormones are increased in PCOS? Decreased?
Anovulation and increased androgen levels occur from increased stimulation on ovarian theca cells from high levels of LH.
FSH is decreased -> therefore ovarian granulosa cells are unable to aromatize androgens to estrogens
(high LH/FSH ratio)
What is defective in Lesch-Nyhan syndrome? What results?
X-linked recessive defect in Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) which is responsible to convert hypoxanthine and guanine to IMP and GMP -> decreased purine salvage, increased purine synthesis, hyperurecmia, and hyperuricuria
What is the MoA of doxycycline? What other drugs act here?
Tetracyclines bind and inhibit 30s subunit of bacterial ribosomes by blocking aminoacyl-tRNA from entering ribosomal acceptor site (bacteriostatic - rikketsia, mycoplasma pneumo, and chlamydia)
Aminoglycosides
What is the MoA of Puromycin?
aminonucleoside antibiotic w/ a structure analogous to aminoacyl-tRNA -> premature release of unfinished polypeptide chains
What drug would be useful to cause pupillary constriction in a denervated eye?
Pilocarpine (or other cholinergic agonists) -> Acetylcholinesterase inhibitors would not be useful because they require Ach to be present in the synaptic cleft
What occurs in Gaucher’s disease and what are the presenting symptoms?
Most common lysosomal storage disorder (jews) -> glucocerebroside deposition in lysosomes of macrophages (normally should be degraded by glucocerebrosidase) giving wrinkled tissue paper appearance
Sx = hepatosplenomegaly, anemia, thrombocytopenia, bleeding, oseopenia, bone pain and bone fractures
Which fungus forms conidiophores w/ a terminal vesicle and outwardly radiating phialides and conidiospores attached in a broom-like appearance?
Aspergillus fumigatus
What occurs in bacterial transformation, conjugation and transduction?
Transformation = process where bacteria take up naked DNA from environment (if DNAse was added to solution, it would prevent bacteria from doing this)
Conjugation = DNA passed by direct cell to cell contact
Transduction = bacteriophage mediated transport
What is the purpose of the cooling phase in PCR?
Allows primer to bond because lower temperature is preferred for hydrogen bonding (higher temps cause DNA to denature and Taq Pol to be more active)
What does a consistently delayed onset of sleep during the work week (e.g. at 3 am) w/ excessive day time sleepiness, and normal weekends with no sleepiness indicate?
Circadian Rhythm Sleep Disorder (late onset during week when have to get up early for work causes sleepiness; during the weekend the patient can sleep in, completing the sleep cycle and thus not feeling tired)
What does fatigue, decreased exercise tolerance, prominent conjunctival pallor, white patches on gingiva and buccal mucosa, and hemorrhages on fundoscopic exam hint at?
Acute leukemia (should see blast cells on peripheral blood smear and patient would have pancytopenia, including thrombocytopenia leading to hemorrhages and leukopenia leading to candida infections -> white patches on mouth)
What is the virulence factor in Aspergillus that can lead to severe infection in the lung forming cavitary lesions and widespread infection in the body?
Immunocompromised patient -> Severe necrotizing pneumonia -> vascular invasion facilitates hematogenous spread to other organs
What organ depends on a lipid-rich cell wall as a virulence factor?
Mycobacteria
