UWORLD Flashcards
achondroplasia mode of inheritance
AD
function of DNA polymerase 3 vs DNA polymerase 1
polymerase 3 - 5 to 3 DNA synthesis and 3 to 5 exonuclease (“proofreading”) activity
polymerase 1 - 5 to 3 DNA synthesis and 5 to 3 exonuclease…removes RNA primer and replaces with DNA
MOA endopeptidase inhibitor?
aka NEPRILYSIN inhibitor….inhibits the inhibtor of several peptide hormones including brady kinin, glucagon, enkephalins, natriuetic peptide (ANP secreted by atrial cardiomyocytes)…can be used to lower BP through peripheral vasodilation, natruresis and diuresis
specific RNA consisting of 90 ish nucleotides, contains high amounts of bases incluidng dihydrouridine, pseudouridien, and ribothymidine, and secondary structure arises from base paring within chain…what type of RNA?
tRNA!!!
has CCA tail at 3’ end
How does total lung capacity, residual volume, forced vital capacity, and forced expiratory volume and diffusing capacity change when you age?
When you age, chest compliance decreases (stiffening ribs), but lung compliance increases (floppy alveoli) so they counterbalance each other.
TLC: unchanged RV: increases FVC: decreases FEV1: decreases Diffusing capacity: decreases
Which metabolic processes houses enzymes that live in exclusively in mitochondria, cytosol, and both?
mitochondria: beta oxidation of fatty acids, citric acid cycle, carboxylation of pyruvate (gluconeogenesis)
cytosol: glycolysis, fatty acid synthesis, pentose phosphate pathway
both: heme synthesis, urea cycle, gluconeogensis
Which cells have highly developed smooth endoplasmic reticulum?
any cells that are the site of steroid synthesis and detoxification of drugs/poisons
HEPATOCYTES and steroid hormone producing cells of ADRENALS and GONADS
Describe the cardiac myocyte AP
rapid depolarizaiton (phase 0) - voltage gated Na channels open initial rapid repolarizaiton (phase 1) - rapid closure of Na channels plateau (phase 2) - distinctive feature!, opening L-type Ca channels and closure of K channels (membrane highly permeable to Ca and not as permeable to K) late rapid repolarizaiton (phase 3) - closure of Ca channels and opening of K channels (K efflux from cell resotres membrane resting potential to -90mv as opposed to -75 in skeletal muscle)
Infection with what organisms can result in formation of cold agglutinin? (clumping of blood in ice as a response during low temperature)
Mycoplasma pneumoniae (also EBV infection and hematologic malginancy)
infant presents with white pupils, sensory neural deafness, and patent ductus arteriosus
congenital rubella syndrome
prevent with LIVE ATTENUATED RUBELLA VIRUS VACCINE
Patients with CGD are vulnerable to catalase positive organisms due to their NADPH oxidase deficiency…what are common catalase positive organisms?
burkholderia cepacia, serratia, nocardia, staph AUREUS, aspergillus
What is the main virulence factor of Staph aureus and it’s MOA?
Protein A, found in peptidoglycan cell wall binds to Fc portion of IgG preventing complement activation, opsonizaiton, and phagocytosis
Describe mitochondrial DNA
resembles prokaryotic (circular) and codes for many different things including ribsomal and transfer RNA
What are the 3 ketones
acetoacetate, acetone, and hydroxybutyrate
Myopathy, cardiacmyopathy, hypoketotic hypoglycemia, low carnitine…dx and pathophys?
primary carnitine deficiency…cannot transport fatty acids from cytosol to mitochondria for breakdown/oxidation into acetyl CoA for TCA cycle…therefore body cannot generate KETONE bodies (aceloacetate, acetone, hydroxybutyrate) when glucose is low
baby initially well…develops poor feeding, hypotonia, large anterior fontanelle, large tongue/macroglossia, umbilical hernia
congenital hypothyroidism
upslanting palpebral fissures, heart murmur, single palmar crease, face hyoplasia, flat nose…dx and 3 ways to get it
DOWNS
- meotic non disjunction (95%)
- unbalanced translocation
- mosaicism
midline defects in infant, microcepahly, cleft lip, omphalocele, holoprosencephaly
patau syndrome trisomy 13
Where are very long fatty acid chains and odd numbered brainching chains metabolized?
perioxosomes
deficiency will lead to neurologic defects
patient being treated for TB presents with microcytic anemia diagnosed with prussian blue stain…dx, deficient enzyme, causative factor
sideroblastic anemia (look for rings)... isoniazid blocks pyridoxine phosphokinase leading to vitB6 (pyrodoxine deficiency) which is a necessary cofactor for ALA synthestase (rate limiting step of heme synthesis)...this causes the sideroblastic anemia
Describe the virology of HBV
capsid contains partial double stranded circular DNA that has an enzyme in its virion with RNA dependent DNA polymerase
B2 riboflavin is important for which cofactors (which are used in which reaction?)
FAD and FMN (flavin dinucluetide and flavin mononucleutide) which are both used in the elctron transport chain…esp succinate dehydrogenase reaction
How do RAS genes work?
Go from inactive (GDP bound) to active (GTP bound) via receptor tyrosinase kinase leading to cell proliferation….when mutation in RAS occur, GTP active bound proliferates leading to uncontrolled cell growth and CANCER
fever, facial pain, nasal eschar in patient with DKA…dx, diagnosis, rx?
murmycosis
dx with mucosal biopsy (usu. neg blood culture), will see right angle branching hyphae on biopsy
treat with amphotericin B and surgical debridement
Patient back from vacation comes in with papulopustular rash on trunk/extremities…pus shows gram negative rods, oxidase positive,
pseudomonas
hot tub folliculitis
risk factors and protective factors for BRCA positive ovarian cancer
risk = anything that increases frequency of ovulation/shedding protective = the opposite
risk - BRCA, nulliparity, infertility
protective- oral contraceptives, multiparity, breast feeding
GET OUT THERE AND GET KNOCKED UP YO!
Transplant patient, develops non productive cough and low grade fevers…histology shows inclusion bodies (owl eyes)
CMV
enveloped double stranded DNA virus
UTI in patient with indwelling catheter…culture shows NON lactose fermenting, gram negative rod
pseudomonas
SUMMER camp, bunch of children sick with fever, bilateral conjunctival injection, cough, NO RASH, erythematous oropharynx
adenovirus
In primary osteoporosis, how are calcium and PTH levels changed?
THEY AREN’T
if not due to underlying medical disorder, serum Ca and PTH are usually normal
Which vessels have the highest risk of atherosclerosis?
coronary arteries and lower abdominal aorta
immunocompromised patient with pneumonia and brain abscess, gram positive acid fast branching, catalase positive
nocardia
Increased resistance to HAART in HIV treatment is due to mutations in what type of genes
pol genes
patient with DVT develops stroke…increased risk in what conditions?
this is paradoxical emboli that cased the stroke…anything that leads to pathological connection between right and left heart cavities can increase risk of this (patent foramen ovale or ATRIAL SEPTAL DEFECT)
remember atrial septal defects are associated with wide splitting S2 that doesn’t change with inspiration
Describe action of RAAS system and where things occur
low renal blood flow (i.e. from CHF) -> renin produced by juxtaglomerular apparatus activated and converts angiotensinogen (made by liver) into angiotensin 1 in SYSTEMIC CIRCULATION -> then angiotensin 1 is converted to angiotensin 2 in small pulmonary vessels causing vasoconstriction and increase in BP as well as targets the adrenals to make more ALDOSTERONE ->this then increases Na reabsorption
girl born with partially fused labial scrotal folds and bilateral hypoplasa of adrenals…46 XX karyotype…dx and MCC
congenital adrenal hyperplasia
90% due to 21 HYDROXYLASE deficiency which converts progesterone to 11 deoxycorticosterone in zona glomerulosa; and 17 oh progesterone to 11 deoxycortisol in zona fasiculata
dx with high amount of 17 OH progesterone in serum
MOA and target of c perferigens (gas gangrene) toxin
attacks lechitinase, component of PHOSPHOLIPID membranes
how to dx essential fructosuria?
+ urine copper reduction test
(-) glucose oexidase
mode of inheritance for spinal bifida
MULTIFACTORIAL (take your folic acid bitch!)
cardiac defects seen in 22q11
interuppted aortic arch and tetraology of fallot
MOA septic shock in causing lactic acidosis
decreased tissue perfusion = impaired oxidative phosphorlyation = pyruvate is shunted to lactate following glycolisis = LACTIC ACIDOSIS
hyperphenylalaemia + elevated prolactin despite tyrosine supplementation
deficiency of dihydrobiopterin reductase (NOT CLASSIC PKU)…these patients are low in dopamine too
elderly man with progressive corneal clouding and hx of poorly controlled DM
deficiency in sorbital metabolism (aldolase B or sorbitol dehydrogenase deficiency)
older child with normal growth with isolated cataracs
galactokinase deficiency (fructokinase deficiency doesn’t cause cataracs)
how to dx Hartnup disease
increased neutral amino acids in urine
Why do hematomas turn green?
heme is degraded into biliverdin by HEME OXYGENASE (then into unconj bilirubin by biliverdin reductase)
Which apolipoprotein is associated with late onset Alzheimer’s
ApoE
child after long period of not eating develops lethargy, vomiting, no ketones, low glucose
hypoketotic hypoglycemia likely from ACYL COA DEHYDROGENASE DEFICIENCY (most common)
how does hyperammoniemia affect neurotransmission?
ammonia crosses blood brain barrier and interferes glutamine/glutamate exchange (glutamine will accumulate in astrocytes) and will interfere with neurotransmission
what to homeobox/hox genes encode for?
DNA binding transcription factors/modulators which play important role in cranial/caudal axis
features of Turner syndrome
primary amenorrhea (MCC CAUSE) short stature webbed neck broad/shield chest with widely spaced nipples coarctation of aorta/bicuspid aortic valve horseshoe kidney OVARIAN DYSGENEISIS/STREAK OVARY 45 XO
What determines the degree of severity for Tetraology of Fallot?
degree of RVOT (bigger obstruction shunts more deoxygenated blood into circulation…lesser obstructions and babies can be acyanotic)
Features of SCID
severe bacterial and viral infections in infancy
CHRONIC DIARRHEA
mucocutaneous CANDIDIASIS
presents during infancy
T/F: Localized carcnoid produces symptoms of slushing, watery diarrhea, bronchospasm, and increased urinary excretion of 5-HIAA
FALSE…must be metastatic (i.e. pass through liver)
host cell coinfected with 2 viral strains and later progeny of host contain UNCHANGED PARENTAL GENOME
phenotypic mixing
Why are lung infarctions rare in PE?
if pulmonary artery is occluded…there is COLLATERAL circulation with BRONCHIAL ARTERY (as the bronchial artery still brings in nutrients and can help with gas exchange if pulmonary artery is out)
microangiopathic hemolytic anemia, thrombocytopenia, renal insufficiency, boody diarrhea
HUS from EHEC
synthesis of catecholamines
tyrosine (tyrosine hydroxylase) dopa (dopa decarboxylase) dopamine (dopamine B hydroxylase) norepi (PNMT which is UPREGULATED BY CORTISOL) epinephrine
How to dx strongyloides infection
rhabditiform larvae in the stool (non infectious)
MOA of cornebacterium toxin cauisng psedumembranous pharyngitis
acquires Tox gene via lysogenizaiton (bacteriophage infects host bacterium) by a temperate bacteriophage
antibiotic use-pregnancy/DM/immunosuppression predisposes women to what infection
candida overgrowth (i.e. candida vaginitis) vulvar/vaginal pruiritis and thick white cottage cheese like discharge...budding yeast and pseduohypae
histologic finding of bacterial vaginosis
epithelial cells covered with gram variable rods) CLUE CELLS!!!
What do native CD4 cells need to differentiate into TH1 subtype
IFN gamma and IL 12!!!!!!
remember TH1 subtypes make IL2, IFN gamma for activation of macrophages and CD8 T cells needed for mediation of delayed type hypersensitivity
patient hx of hypothyroidism, weight loss, and hyperpigmentation p/w severe hypotension, abdominal pain/vomiting/weakness…dx and treatment
primary adrenal insufficiency in adrenal crisis…aggressive fluid resusitation and glucocorticoid supplementation (hydrocortisone, or dexmethasone)
MOA of ACE inhibitors in kidneys
decrease angiotensin II therefore DILATING EFFERENT ARTERIOLE and reducing GFR
Findings in Bruton agammaglobulinemia
absent B cells in peripheral blood, decreased Ig of all classes, absent/scanty lymph nodes, recurrent bacterial and enteroviral infections usually starting at 6 months of age…DECREASED CD 19 CD 20
18 YO patient with no a-galactosidase …decreased sweating and neuropathic pain with non blanching red papules highest risk for developing what?
FABRY DISEASE (x linked) cerebrovascular and cardiac disease as well as renal failure *proteinuria nad plyuria)
patient with fatigue, rash, flushing, abdominal cramps…rash worse with rubbing/scratching…large clusters of mast cells psotiive for KIT (CD117)…additional findings?
SYSTEMIC MASTOCYTOSIS usually with mutaitons in KIT receptor tyrosine kinase = excessive histamine release
excessive histamine = syconpe, flushing, hypotension, pruitis, urticaria, increased gastric acid secretion and gastric ulcers
Pregnant mother has low grade fever, maculopapular rash with progression from head down, posterior auricular and suboccipital lymphadenopathy….mother and fetus at risk to develop?
mother: polyarthritis and polyarthlargia
fetus - sensorineural dafness, cataracs, cardiac malformations (PDA)
thyroid nodule with associated high calcitonin, mucosal neuromas/long arms/fingers
MEN 2B
also associated with pheochromocytoma = flushing, diaphoresis, headahces
patient with sickle cell develps exquisite thigh pain and bacteremia due to non lactose fermenting, oxidase negative organism
salmonella osteomyelitis
toxin is a special capsule “Vi angitgen” that protects it from opsonization and phagocytosis
burn patient with Gram negative rods that are oxidase positive and non lactose fermenting
pseudomonas
treat with ceftazidime/cefepime, fluroquinolones, or pipercillin, carbepanems
infant of IV drug use mother with no prenatal care develops oral thrush, interstiitial pneumonia, and severe lymphopenia during first year of life
mother to baby HIV transmission
prevent with ART (reverse transcriptase inhibitor)
Histologic features of PBC and what disease is it similar histologically to?
autoimmune disaese characterized by lymphocytic infiltrates and destruction of small/midsized intrahepatic bile ducts…similar to hepatic graft vs host disease!
What important B cell process happens in germinal center of lymph nodes
isotype switching (VDJ recombination and B cell maturation happen in bone marrow before B cells reach lymph node)
Which immune cells recognize and kill cells with decreased MHC class I antigen cell surface expression (i.e. virus infected cells/tumor cells) and how do they do it?
natural (NK) cells via perforin and granzymes that induce apoptosis in target cell
How do OPG (osteoprotegerin) and RANK effect bone metabolisM?
When RANK binds to RANK-L, more osteoclasts form=more bone turnover/resorption. OPG blocks this binding and slows resorption. Therefore, high OPG/RANK ratio = less osteoclast activity and vise versa
low estrogen lowers this ratio and therefore osteoclast activity predominates
What can you give as a supplement in patient with folate deficiency to lessen erythroid cell apoptosis
thymidine (can bypass dihydrofolate reductase step)
Which area on tRNA the site where aminoacy tRNA synthetase “loads” the appropriate amino acid?
3’ CCA tail = acceptor stem
Which organisms can cause diarrhea with only a small inoculum of bacteria?
camp jejuni, entamoeba histolytica, giardia, and SHIGELLA!!!
immunocompetent PATIENT WITH FEVER, FATIGUE, SPLENOMEGALY, ATYPAL lymphocytosis (no sore throat or lymphadenopathy), negative for horse erythrocyte agglutination
i know you’re thinking EBV but nope
CMV
can also be passed on from blood products
patient with encephalitis (confusion), mobiliform rash, bilateral leg weakness/flaccid paralysis, summertime, febrile.
westnile virus
supportive treatment
patient on medication for Graves disease presents with fever and sore throat?
suspect agranulocytosis from thionamides (methimazole or propylthiouracil)
confirm dx with WBC with diff
neonate with lymphedema and cystic hygroma
think Turner syndrome
patient back from trip in Africa who swam, presents with dysuria and hematuria with bilateral hydronephrosis and bladder wall thickening…dx and vector
schistomiasis
probably from s haematobium eggs from snails in freshwater…attacks urinary
s japonicom and mansoni infect the bowel
C tetani toxin blocks release of what chemicals which lead to disinhibited motor neurons?
GABA AND GLYYYYYCINE!!!!!!!
wide fixed splitting of second heart sound….pt at risk for what irreversible injury to circulation?
pulmonary vessel sclerosis and Eisenmenger syndrome (pulmonary hypertension due to right to left shunting)
NOT RVH (as this is usually reversible)
patient with hx of recent surgery presents with fever, anorexia, nausea, myalgias, arthralgias, rash, extensive liver damage
suspect drug induced liver injury from inhaled anesthetics…assoc with elevated transaminases and elevated prothrombin time
