UWorld Notes Flashcards
A 65 year old male with atrial fibrillation has been taking warfarin and atenolol for one year. Two weeks after starting a new drug he experiences sudden onset hemiplegia. Transesophageal echocardiography reveals a small thrombus in the left atrium. The recently added drug was most likely:
A- penicillin B - Clarithromycin C- Phenobarbital D - Cimetidine E - Nifedipine F - Fluconazole G - Ciprofloxacin
Answer is C - Phenobarbital
The patient has developed complications from chronic atrial fibrillation - a left atrial mural thrombus and a thrmoboembolic stroke - indicating that recently his anticoagualtion with warfarin has been inadequate. Phenobarbital and other barbiturates can induce the hepatic microsomal enzymes (it is a cytochrome p450 inducer), causing increasing metabolism and clearance of warfarin, reducing its anticoagulant activity. Barbiturates may also increase hepatic synthesis of clotting factors.
Name 5 common cytochrome p450 inducers (CYP 450 inducers). What effect will they have on clearance of drugs?
Carbamazepine, Phenobarbital, Phenytoin, Rifampin, Griseofulvin
They will increase metabolism and clearance of hepaticly cleared metabolites.
Name 7 cytochrome p450 inhibitors.
Cimetidine, Ciprofloxacin, Erythromycin, Azole antifungals, Grapefruit juice, Isoniazid, Ritonavir (protease inhibitors).
A 10 year old is brought to the physician for evaluation of short stature. She was an average sized infant but over the past few years her height growth velocity has plateaued. The patient has not menstruated and has no symptoms. She takes no medications, has no alleriges, and received all recommended immunizations. Her mother had menarche at age 14; both of her parents are tall. The patient’s height is at the
Answer: C- Meiotic Nondisjunction
Explanation: Turner syndrome is a genetically heterogenous condition that is most commonly caused by paternal meiotic non-disjunction during gametogenesis. The loss of the parental X chromosome int he sperm results in a missing X chromosome in most or all cells of the offspring. Most affected patients have complete loss of an X chromosome (45,X). Other patientss are missing the X chromosome in some of their cells (mosaicism); this is known as mosaic Turner syndrome (45X/46XX). Some patients have both X chromosomes, but one is abnormally shaped, missing some genetic material, or has structural abnormalities ( ex: X fragments, isochromosomes). Girls with a mixed chromosome pattern may have fewer symptoms if they have some normal XX cells.
The loss of the X chromosome results in a missing SHOX gene, which is responsible for long bone growth. Therefore, patients with Turner Syndrome typically have short stature. Patients with Turner syndrome have additional abnormalities:
- Narrow, high arched palate
- Low set ears
- Low hairline
- Webbed neck
- Coarction of aorta
- Bicuspid aortic valve
- Broad chest w/ widely spaced nipples
- Horse-Shoe Kidney
- Streak Ovaries, amenorrhea, & infertility
Meiotic non-disjunction is also responsible for Klinefelter syndrome and trisomies 13, 18, 21.
What is Robertsonian translocation and give an example
A robertsonian translocation occurs between 2 acrocentric chromosomesl the long arms fuse near the centromeres and the short arms are lost. An unbalanced trisomy 21 (in which one chromosome 14 contains the long arms of both chromosome 14 and 21) is responsible for 3-4% of Down syndrome cases.
What is a frameshift mutation and give an example
A frameshift mutation is a genetic mutation in which a number of nucleotides not divisible by 3 is inserted or removed from the DNA sequence. As a result the reading frame is disrupted and the product of translation is changed.
Familial hypercholesterolemia has been associated with frameshift mutations.
What diseases area a result of trinucleotide expansion (name 4 and their trinucleotide associated)?
Fragile X (CGG) Friedreich ataxia (GAA) Huntington Disease (CAG) Myotonic dystrophy (CTG)
X-Girlfriend’s First Aid Helped Ace My Test
May show genetic anticipation (disease severity inc. and age of onset dec. in successive generations - esp when inherited from a female parent)
What is uniparental disomy and name 2 examples.
Uniparental disomy occurs when an individual inherits 2 copies of a chromosome from one parent and no copies of the chromosome from the other parent. Prader-Willi syndrome occurs in those who have 2 maternal copies of chromosome 15 due to deleted or unexpressed paternal chromosome. Angelman syndrome occurs in those who have 2 paternal copies of chromosome 15 due to deleted or unexpressed maternal chromosome.
Note: BOTH on chromosome 15
Prader-willi = deleted Paternal chromosome
angelMan = deleted Maternal chromosomeq\
List symptoms of Prader-Willi Syndrome
Uniparental disomy on chromosome 15 w/ paternally inherited genes lost.
- Neonatal hypotonia
- Hyperphagia/obesity
- Hypogonadism
- Short stature
- Small hands & feet
- Dysmorphic facies
- Intellectual disability
List symptoms of Angelman Syndrome
Uniparental disomy on chromosome 15 w/ maternally inherited genes lost
- Epilepsy/seizures
- Ataxic gait/tremors
- Inappropriate laughter/smiling
- Poor motor & language development
- Intellectual disability
Describe diabetes insipidus
Diabetes insipidus is a disease characterized by polyuria (excessive urination) and polydipsia (excessive thirst) despite normal blood glucose.These symptoms occur due to impaired antidiuretic hormone (ADH) activity and the resulting production of large volumes of very dilute urine.
Where is ADH synthesized and where is it stored?
ADH or vasopressin is synthesized in the hypothalamus, specifically in the paraventricular and supraoptic nuclei. After synthesis, ADH is transported to the posterior pituitary (hypophysis) for storage and later release into the circulation.
A 47 year old woman is diagnosed with breast cancer metastasized to the bones and liver. She begins treatment with anastrozole. She has no other medical problems and takes no other medications. She does not use tobacco, alcohol, or illicit drugs. Soon after initiating therapy for her cancer, her primary tumor substantially decreases in size. Which of the following is the best explanation for the therapeutic effect?
A- decreased follicular cell stimulation B- decreased androgen synthesis C- decreased androgen aromatization D- impaired ligand-receptor interaction E - Impaired second-messenger action.
Answer: C Decreased androgen aromatization
Estrogen is the main hormone responsible of the growth and development of malignant breast tumors. Aromatase inhibitors are drugs that inhibit the synthesis of estrogen from its androgenic substrate, suppressing estrogen to postmenopausal levels. In the treatment of metastatic breast cancer, aromatase inhibitors are equivalent or superior to tamoxifen.
The aromatase enzyme belongs to the P450 superfamily and is highly expressed in ovarian tissue (ovarian expression of aromatase is gonadoptropin dependent). Aromatase is also present in subcutaneous fat, normal breast tissue, and cancerous breast tissue. In the postmenopausal state, extraovarian aromatase maintains a low level of estrogen in the peripheral circulation.
Aminoglutethimide and fadrozole were the initial aromatase inhibitors. However, these drugs lacked potency and specificity. Third-generation aromatase inhibitors (ie anastrozole, letrozole, and exemestane) are highly selective and potent.
When introduced individually , 2 different mutant strains of adenovirus do not cause cytopathic effects in human cell culture. But when the cultured cells are simultaneously exposed to both mutant strains, a new viral progeny strain is produced that causes cellular enlargement and aggregation. Which of the following most likely contributed to the formation of the progeny viral strain?
a- Reassortment B- Recombination C- Transformation D- Phenotypic mixing E- Interference
Answer: B - Recombination
This scenario describes the exchange of genetic information b/t 2 virus strains that have non-fragmented, double stranded DNA genomes. Such an exchange amounts to recombination, which may be defined as the exchange of genes between 2 chromosomes via crossing over w/in homologous regions. The resulting progeny will have traits no present simultaneously in either parent virus.
Why not these?
a- Reassortment refers to changes in genomic composition that occur when host cells are co-infected w/ 2 segmented viruses that exchange whole genome segments. This process can cause sudden alterations in the surface antigens of the viral progeny as observed with the highly mutagenic influenza virus. Because the adenovirus genome contains non-segmented, double-stranded DNA, it does not engage in reassortment.
c- Transformation is generally defined as the uptake of naked DNA by a prokaryotic or eukaryotic cell. In virology, this term may also be used to describe the incorporation of viral DNA into a host cell chromosome. Transformation alters the genetic composition of the host cell, but typically causes no genomic change in progeny virions.
d- Phenotypic mising refers to co-infection of a host cell by 2 viral strains, resulting in progeny virion that contains nucleocapsid proteins from one strain and the genome of the other strain. In this case since neither virion strain was cytopathic (even though both strains could apparently insert their genomes into the host cell line), rearrangement of the capsid proteins around either unchanged genome wouldn’t not be expected to confer new cytopathic virulence to the progeny virions
e- Interference is the inhibition by one virus of the replication and /or release of a second virus that is infecting the same cell.
What coenzymes are needed for pyruvate dehydrogenase? What other enzyme also requires these co-factors?
Thiamine pyrophosphate (TPP), Lipoic acid, CoA, FAD, and NAD.
Alpha-ketoglutarate dehydrogenase (takes alpha ketoglutarate –> succinyl CoA in the TCA cycle) also requires these cofactors.
What is a necessary cofactor for agininosuccinate synthetase?
ATP
[UREA CYCLE]
Citrulline + Aspartate — (Argininosuccinate synthetase + ATP) –> argininosuccinate
What disease is the result of a deficiency of argininosuccinate synthetase? What cofactor might you be missing?
Citrullinemia - a urea cycle disorder.
You may be missing the necessary ATP
A deficiency of methylmalonate mutase can result in what disease? What vitamin is this enzyme dependent on?
Methylmalonic aciduria b/c of increased circulating levels of methylmalonic acid.
B12 dependent
Homocystinuria results from what deficiency? What is a characteristic symptom?
Cystathionine synthase
Characterized by premature atherosclerosis.
What are the 2 ways homocysteine is disposed of by the body?
1) conversion to cysteine by the combined actions of 2 vitamin B6 requiring enzymes: cystathionine synthase and cystathionase
2) conversion to methionine by a folate and vitamine B12 dependent process
Orotic aciduria results from a deficiency in what enzyme? What is the cofactor required? Synthesis of what will be effected?
Orotic aciduria results from a deficiency of the enzyme orotate phosphoribosyl transferase. Needs glutathione as a coenzyme. Results in defective PYRIMIDINE synthesis.
Poststreptococcal glomerulonephritis is what type of hypersensitivity?
Type III
During infx antibodies form against antigens expressed by nephritogenic strains of group A beta hemolytic stretococci (ie strep pyogenes). These anti-streptococcal antibodies combine w/ streptococcal antigens to form immune complexes that are deposited along the glomerular basement membrane. These deposits can be visualized as electron-dense subepithelial “humps” on EM and as granular deposits w/in the mesangium & glomerular capillary walls on IgG and C3 immunofluorescence
Bilateral renal masses composed of fat, smooth muscle, and blood vessels are detected in a young woman. The patient is most likely to suffer from which of the following additional findings?
a- brain hamartomas and ash-leaf skin patches
b- multiple peripheral neurofibromas and cafe-au-lait skin spots
c- bilateral acoustic neuromas
d- cerebellar hemangioblastomas and liver cysts
e- capillary angiomas of the face choroid
f- multiple telangiectasias of the skin and mucosa
Answer: A - brain hamartomas and ash-leaf skin patches
Short answer: patient has bilateral renal angiomyolipoma which is closely associated with tuberous sclerosis. Other symptoms of tuberous sclerosis include brain hamartomas and ash-leaf skin patches
Full explanation:
Renal angiomyolipoma is a benign tumor composed of blood vessels, smooth muscle, and fat. These tumors can be diagnose diwth an abdominal CT scan, as the density of fat is less than that of water.
Angiomyolipomas are associated w/ tuberous sclerosis. In patients w/ bilateral renal angiomyolipomas the incidence of tuberous sclerosis is 80-90%. Tuberous sclerosis is an autosomal DOMINANT condition characterized by cortical tubers and subependymal hamartomas in the brain with consequent seizures and mental retardation. Cardiac rhabdomyomas, facial angiofibromas, and leaf shaped patches of skin lacking pigmant can also occur.
Why not these?
B- Multiple peripheral meurofibromas & cafe-au0lait skin –> neurofibromatosis type 1 (an AD disorder also w/ coptic gliomas & pigmented nodules of the iris (Lisch nodules)
C- bilateral acoustic neuromas –> Neurofibromatosis type 2 (AD disorder that may also develop multiple meningiomas, gliomas, and ependymomas of the spinal cord)
D - Cerebellar hemangioblastomas & liver cysts –> Von Hippel Lindau syndrome (may also have retinal hemangiomas & are at high risk for bilateral renal cell carcinoma)
E- Capillary angiomas of the face choroid –> Sturge-Weber syndrome a rare congenital vascular disorder characterized by a facial port-wine stain and leptomeningeal capillary-venous malformation
F- multiple telangiectasias of the skin and mucosa –> hereditary hemorrhagic telangiectasia (Osler-Rendu-Weber syndrome). Typical presentation is recurrent epistaxis (bloody noses) and gastrointestinal bleeding (melena)
A 23 year old male hospitalized for confusion adn seizures is treated with intravenous high-dose acyclovir. On the 3rd day of hospitalization, his serum creatinine level increases to 3.4 mg/dL from a baseline of 0.9 mg/dL at admission. The observed finding could have been potentially prevented by which of the following?
A- Careful allergy history taking B- Monitoring the blood drug levels C- Pre-treatment with allopurinol D- Pre-treatment with prednisone E- Aggressive intravenous hydration
Answer: E - Aggressive intravenous hydration.
Why:
The acute elevation of this patient’s serum creatinine is most likely secondary to acyclovir nephrotoxicity, a phenomenon that occurs in 5010% of patients who recieve the drug intravenously. Acyclovir is exreted principally in the urine via glomerular filtration and tubular secretion. When the acyclovir concentration in the collecting duct exceeds its solubility, crystallization, crystalluria, and renal tubular damage may result. In most cases, this toxic complication is transient and can be prevented (as well as treated) with adequate hydration and dosage adjustment, which includes slowing the rate of IV infusion.
A 32 year old caucasian female presents to your office complaining of mood swings, palpitations, excessive sweating, and easy fatigability. On physical examination she has moderate exophthalmos and fine tremors when holding her hands outstretched. She reports that these symptoms interfere significantly with her daily activities. Which of the following symptoms is most likely to persist despite propranolol therapy?
a- Palpitations B- Hand tremor C- Fatigability D- Mood swings E- Exophthalmos
Answer: E - Exophthalmos
Signs and symptoms of Graves disease thyrotoxicosis include palpitations, nervousness, easy fatigability, fine tremor, diarrhea, hyperhidrosis (excessive sweating), heat intolerance, weight loss, hyperreflexia, dermopathy, and opthalmia (inflammation of the eye). Thyroid ophthalmia is caracterized by exophthalmos (bulging of eye anteriorly out of orbit), conjunctival hyperemia (excess blood in vessels of conjunctiva), and periorbital edema. The exophthalmos that occurs in patients with thyrotoxicosis is the result of increased soft tissue mass w/in the bony orbit due to enlargement of the extraocular muscles from myositis, fibroblast proliferation and overproduction of ground substance in response to antithyroid antibodies.
Beta-adrenergic antagonists like propranolol are frequently used to treat the acute symptoms of thryotoxicosis in preparation for thyroid surgery. Beta-blockers can relieve those symptoms related to the sympathetic nervous system, namely tachycardia, hypertension, and tremor. Mood lability and fatigue may resolve as well after the symptoms stemming from sympathetic overactivation have subsided. Thyroid ophthalmia, however, is not affected by beta-adrenergic blockade. The ocular manifestations of graves thyrotoxicosis sometimes respond to corticosteroid therapy.
What grows on blood agar containing bile and hypertonic saline?
Blood agar containing bile and hypertonic saline can be used to culture entercocci and to differentiate entercocci from the nonetercoccal Group D Stetoccoci. The enterocci include E. faecalis and E. faecium and are able to grow in the presence of both bile salts and 6.5% hypertonic saline. The nonenterococci include Stetococcuus bovis and Streptococcus equinus. Nonenterococcal Group D streptococci grow in the presence of bile but NOT in the presence of hypertonic saline.
Which enterocci will grow in the presence of bile? Which in the presence of bile and 6.5%hypertonic saline?
Enterococci and nonenterococcal Group D Streptococci will grow in the presence of bile, but only enterococci will grow in the presence of 6.5% hypertonic saline and bile (ie E. faecium and E. faecalis).
A 24 year old caucasian male is admitted to the hospital with a 1 week history of fever, cough, and chest pain. Lung auscultation reveals crackles over the right lower lung lobe. When placed in an upright glass tube his anticoagulated red blood cells fall at a rate of 35 mm per hour. This finding is most likely related to the action of which of the following substances?
a) Bradykinin
b) Leukotriene B3
C) Erythropoietin
D) IL-6
E) Platelet activating factor
F) Thromboxane A2
Answer: D - IL-6
When an injury occurs, local neutrophils and macrophages release tumor necrosis factor-alpha, IL-1, and IL-6 into circulation. These particular cytokines mediate systemic inflammatory response, in part by stimulating hepatic production of acute phase reactants (ie fibrinogen, ferritin, C-reactive protein, serum amyloid A, serum amyloid P, complement factors). Many acute phase proteins bind to microbes and fix complement. When increased, the acute-phase protein FIBRINOGEN causes erythrocytes to form stacks (rouleaux) that sediment at a faster rate than do individual erythrocytes. This aggregation rate is termed the erythrocyte sedimentation rate or EST and is a non-specific marker of inflammation.
Normal ESR male = 0-15mm/hr; female= 0-20mm/hr
In this question the ESR is 35mm/hr which is farther faster.
What test has bacitracin been replaced w/ bc it is more specific?
Pyrrolidonyl arylamidase (PYR) test
What bug has a positive pyrrolidonyl arylamidase (PYR) test?
Strep pyogenes (b/c bacitracin sensitive)
Where is GABAa located, what’s its structure and what effect does it have when stimulated? What are some drugs that work at this site?
GABAa Location: Brain Structure: Ion Channel Effect of Stimualtion: CL- influx Drugs that act on: Benzodiazepines (ie lorazepam), barbiturates (ie phenobarbital), alcohol, zolpidem
NOTE: GABAa is same as GABAc except GABAc is located in the Retina (“you need C to see”)
Where is GABAb located? What’s its structure and what effect does it have when stimulated? What are drugs that work at this site?
GABAb
Location: Brain
Structure: G-Protein
Effect of stimulation: K+ efflux, dec Ca influx, inhibit adenylyl cyclase
Drugs that act on: Baclofen (activates @ spinal cord level –> skeletal muscle relaxation esp used for back pain)
Where is GABAc located? What’s its structure and what effect does it have when stimulated?
GABAc
Location: Retina
Structure: Ion channel
Effect of stimulation: Cl- influx
NOTE: Same as GABAa except located in the eye.
“You need C to See cuz its got an ION channel” - get it? EYE-on or ION? lol
Which GABA receptor(s) is/are found in the eye?
GABAc
Which GABA receptor(s) is/are found in the brain?
GABAa & GABAb
Which GABA receptor(s) is/are ion channels?
GABAa & GABAc
Which GABA receptor(s) is/are G-proteins?
GABAb
Which GABA receptor(s) cause an efflux of K and dec influx of Ca and inhibit adenylyl cyclase?
GABAb
Which GABA receptor(s) cause influx of Cl?
GABAa & GABAc
Which receptors do benzodiazepines and barbituates work at?
GABAa
Which receptor does Baclofen work at?
GABAb
Von Hippel Lindau syndrome is a genetic disease found at which chromosome?
VHL - chromosome 3
Von Hippel Lindau disease has what type of inheritance?
VHL is autosomal DOMINANT
What are some key characteristics of Von Hippel-Lindau syndrome?
Capillary hemangioblastomas in the retina and/or cerebellum, congenital cysts and/or neoplasms in the kidney liver, and pancreas,
Von hippel lindau syndrome caused by what?
Deletion of VHL gene on chromosome 3. The gene is a tumor suppressor gene that marks molecules for degradation by ubiquitin most importantly hypoxia induced factor (HIF) which in response to hypoxia causes angiogenesis (formation of new vessels). If VHL not around, HIF will remain in circulation –> tumors of blood vessels (hemangioblastomas) in retina, medulla, or cerebellum. Also puts patient at risk for bilateral renal cell carcinoma and pheochromacytomas
VHL patients are at risk for what?
Bilateral renal cell carcinoma and pheochromacytomas
Von Recklinghausen’s disease is also known as what?
Neurofibromatosis type 1
Neurofibromatosis type 1 is also known as what?
Von Recklinghausen’s disease
Neurofibromatosis type 1 mutation is found at what chromosome?
Chromosome 17
What are characteristics of Neurofibromatosis type 1/Von Recklinghausen’s disease?
Patients develop neurofibromas, optic nerve gliomas, lisch nodules (pigmented nodules of the iris) and cafe au lait spots (hyperpigmented cutaneous macules).
What disease is characterized by the presence f capillary hemangioblastomas in the retina and/or cerebellum as well as congential cysts and/or neoplasms in the kidney, liver, and pancreas?
Von Hippel Lindau disease
What disease is characterized by patients developing neurofibromas, optic never fliomas, lisch nodules, and cafe au lait spots?
Von Recklinghausen’s disease aka Neurofibromatosis type 1
What is a lisch nodule?
A pigmented nodule of the iris found in neurofibromatosis type 1
What type of inheritance is found in neurofibromatosis type 2?
Autosomal dominant
What type of inheritance is found in neurofibromatosis type 1?
Autosomal dominant
What chromosome is the mutation for neurofibromatosis type 2 found at?
Chromosome 22
What are some common findings in neurofibromatosis type 2?
Bilateral acoustic schwannomas, juvenile cataracts, meningiomas, and ependymomas
Which autosomal dominant hereditary disease can cause hearing loss and cataracts at young ages?
Neurofibromatosis type 2
What disease is known for bilateral cranial nerve VIII schwannomas and multiple meningiomas and juvenile cateracts?
Neurofibromatois type 2
Sturge-Weber syndrome is also known as what?
Encephalotrigeminal angiomatosis
Tuberous sclerosis has what type of inheritance?
Autosomal dominant
Tuber sclerosis is caused by what?
Mutation in tumor suppresor gene TSC2
Tuber sclerosis is known for what finding?
Numerous benign hamartomas (cortical and subependymal, and more!), cutaneous angiofibromas (adenoma sebaceum), visceral cysts (ie kidney, liver, pancreatic), renal angiomyolipomas, and cardiac rhabdomyomas.
What is a hamartoma?
A benign focal malformation that resembles a neoplasm, but is not a malignant tumor and grows at same rate and tissue type as surrounding tissue but in a disorganized mass
