Uworld 7 Flashcards
What does IL-12 do?
stimulates the differentiation of “naive” T helper cells into the Th1 subpopulation
rickets bones look like what?
excess of unmineralized osteoid matrix and epiphyseal (growth plate) cartilage
Low vitamin D leads to hypocalcemia and/or hypophosphatemia due to reduced intestinal absorption of these minerals; PTH is markedly elevated to mobilize calcium from bone to the bloodstream
2month old - initially no ssx; then impaired metabolism, slowing of physical and mental activity (lethargy, poor feeding, constipation, hypotonia)
non-pitting edema (puffy face), umbilical hernia, protruding tongue, and a large anterior fontanelle
congenital hypothyroidism
dystrophic calcification is considered a hallmark of
cell injury and death, occurring in all types of necrosis in the setting of normal calcium levels
bacterial mRNA can be polycistronic, meaning that…
what is an example
one mRNA codes for several proteins
bacterial lac operon, which codes for the proteins necessary for lactose metabolism by E. coli; the transcription and translation of these bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements
What antiarrhythmic has less of a chance of inducing torsades while prolonging the QT interval?
amiodarone
What is the MC cardiac defect in pts with down syndrome?
complete atrioventricular (AV) canal defect
mutations in frataxin, a mitochondrial protein important in iron homeostasis and respiratory function cause
Friedreich ataxia
spinocerebellar degeneration and is associated with hypertrophic cardiomyopathy
What five receptors regulate vomiting reflex?
Which ones are targets for reducing N/V in chemo?
- M1 muscarinic
- D2 dopaminergic
- H1 histamine
targets in chemo pts:
- 5-HT3 serotonergic
- neurokinin 1 (NK1)
a false aneurysm or pseudoaneurysm is…
result of a breach in the continuity of all 3 layers of a blood vessel (or heart), leading to blood leakage and hematoma formation outside the vascular wall; resulting hematoma is then contained within a sac of connective tissue surrounding the original point of arterial wall rupture
medial degeneration is characterized by …
the fragmentation of elastic tissue (basket weave pattern) and separation of the elastic and fibromuscular components of teh tunica media by small, cleft-like spaces that become filled with amorphous extracellular matrix
what is the most common trigger for paroxysmal AF?
aberrant electrical foci in the pulmonary veins near their ostia into the left atrium
What cells are seen in follicular lymphoma?
What translocation is commonly seen?
predominantly centrocytes (small cleaved cells) and fewer numbers of centroblasts (large noncleaved cells)
t(14:18) resulting in overexpression of bcl-2
CK release is related to what?
reperfusion injury - secondary to oxygen free radical generation, mitochondrial damge, and inflammtion - resulting in cell membrane damage, allowing creatine kinase to leak out of the cell
during the first few weeks of embryogenesis, hemoglobin is synthesized by the yolk sac and contains…
zeta or epsilon globin chains
HbF production begins at … weeks and replaces all embryonic Hb by…. weeks
8 weeks
14 weeks
sorbitol dehydrogenase converts sorbitol into
fructose
What are the two most important acid buffers in urine?
HPO4 ^2- and NH3
what are features of atypical MDD and what might be a drug to treat this?
increased appetite and sleep, leaden paralysis, rejection sensitivity, and mood reactivity
MAO-I like phenelzine or tranylcypromine
What does neprilysin do?
Why would you rx a neprilysin inhibitor in heart failure?
is a metalloprotease that cleaves and inactivates ANP and BNP
this would lead to increased levels of ANP and BNP and promote beneficial effects in heart failure - increasing urinary sodium excretion
Why does someone with sarcoid have hypercalcemia?
1-alpha hydroxylase expression in activated macrophages in the lung and lymph nodes causes PTH-independent production of 1,25-dihydroxyvitamin D
increased intestinal absorption of calcium and subsequent hypercalcemia
What interleukins play an active role in the pathogenesis of psoriasis?
IL-12 and IL-23
H. pylori in the gastric antrum will cause…
H. pylori in the gastric corpus/body will cause…
Unlike antral-predominant disease, coprus predominant disease is a/w….
duodenal ulcers
gastric ulcers
metaplasia and malignancies (eg gastric lymphoma, adenocarcinoma)
renal biopsy showing rounded/polygonal cells with abundant clear cytoplasm which is characteristic of…
where does this originate?
renal clear cell carcinoma (MC form)
originates from proximal tubular epithelial cells
paroxysmal nocturnal hemoglobinuria is usually due to what mutated gene?
what does this gene normally do?
what does this protein do?
What happens without it?
phosphatidylinositol glycan class A (PIGA) gene
helps synthesize the glycosylphosphatidylinositol (GPI) anchor protein
this protein helps attach several cell surface proteins (eg CD55 decay accelerating factor, CD59 MAC inhibitory protein) that inactivate complement
without, there is uncontrolled complement-mediated hemolysis
single most important risk factor for the development of intimal tears leading to aortic dissection?
hypertension
What is Buerger disease?
thromboangiitis obliterans, a vasculitis of medium and small arteries, principally the tibial and radial arteries
What are the predominant cells found in granulomas?
epitheliod histiocytes and multinucleated Langhans giant cells
What is the essential amino acid for pts with PKU? Why?
tyrosine
they have an inability to convert phenylalanine to tyrosine by the phenylalanine hydroxylase system
low serum levels of C1 esterase inhibitor are diagnostic of…
what is the pathophys behind this?
hereditary angioedema
C1 esterase inhibitor suppresses activation of C1 complement component and therefore the rest of the classic complement pathway;
it also inactivates kallikrein, which catalyzes the conversion of kininogen to bradykinin; in hereditary angioedema, activate kallikrein and bradykinin levels are increased;
Bradykinin, C3a, and C5a mediate angioedema by increasing vasodilation and vascular permeability
What part of complement will be low in C1 esterase inhibitor deficiency?
C4
What drugs are CI in C1 esterase inhibitor deficiency?
ACE inhibitors
The sciatic foramen is divided into greater and lesser sciatic foramina by what ligament?
sacrospinous ligament
What structures run above and below the piriformis through the greater sciatic foramen?
- above the piriformis
- superior gluteal vessels
- superior gluteal nerve
- below the piriformis
- inferior gluteal vessels
- internal pudendal vessels
- multiple nerves, including sciatic
PNH is caused by an acquired mutation of the PIGA gene within clonal population of multipotent hematopoietic stem cells. This gene is involved in the synthesis of the….
What is the importance of this?
glycosylphosphatidylinositol (GPI) anchor
a glycolipid necessary for the attachment of several cell surface proteins, including CD55 (decay accelerating factor) and CD59 (MAC inhibitory protein)
these proteins help inactivate complement and prevent the membrane attack complex from forming on normal cells
Absence of GPI anchor results in CD55 and CD59 deficiency and ….
when does this occur?
complement mediated hemolysis
more often at night because complement activity is increased during sleep to lower blood pH
histologically, what does silicosis appear as?
birefringent silicate particles within dense, whorled collagenous nodules surrounded by dust-laden macrophages
What does silicosis look like on XR?
numerous small, rounded nodules predominant in upper lobes; calcification of the rim of hilar nodes (eggshell calcification) may also be seen
What is the MC extraintestinal manifestation of Entamoeba histolytica infection?
What is common with invasive strains?
single amebic liver absecess in the R lobe of the liver
invasive strains are more likely to have amebic proteases that degrade host extracellular membranes and secretory IgA
also demonstrate contact-dependent cytotoxicity, whereby an amebic lectin binds the host cell, introduces an amebic porin into the host cell membrane and causes cell lysis
RBC fragments, burr cells and helmet cells are consistent with…
What is this a result of?
traumatic hemolysis
either microangiopathic hemolytic anemia or mechanical damage (eg prosthetic valve)
How does Shigella invade the GI mucosa?
How does it cause damage?
gains access to microfold cells in ileal Peyer patches through endocytosis
then it lyses the endosome and spreads laterally into other epithelial cells, causing cell death and ulceration wiht hemorrhage and diarrhea
What is the MC GI disorder in pts with CF?
How does this occur?
pancreatic insufficiency
mutations in CFTR gene lead to thick, viscous secretions in the lumens of the pancreas, resulting in obstruction, inflammation, and subsequent fibrosis
clinical - steatorrhea, failure to thrive, and deficiency of fat-soluble vitamins
What does dobutamine do on the heart?
mimics the effects of exercise and increases myocardial oxygen demand
used during stress testing to provoke areas of ischemic myocardium, which can be recognized on imaging by a localized and transient decrease in contractility (ie wall motion defect)
blistering skin rash in young children with tan- to honey-colored crusts;
dx?
what causes this blistering?
Bullous impetigo - S. aureus
caused by exfoliative toxin A, which targets desmoglein 1 in epidermal cellular junctions and causes a loss of cell adhesion
thin, myelinated nerve fibers whose free nerve endings detect temperature and nociceptive stimuli; associated with acute (sharp) pain and constitute the afferent portion of the reflex arc that mediates withdrawal from noxious stimuli
A-delta fibers
Both Pacinian corpuscles and Ruffini’s end organs are innervated by
myelinated A-beta fibers
Adverse effect of oxygen therapy in neonate?
retinal damage
temporary local hyperoxia in the retina is thought to induce changes that cause up-regulation of proangiogenic factors such as VEGF upon return to room air ventilation - can result in neovascularization and possible retinal detachment with blindness may result
aka retinopathy of prematurity or retrolental fibroplasia
the toxicity of cyanide is dependent on its ability to bind
ferric iron (Fe3+) with high affinity, inhibiting cytochrome c oxidase in the mitochondria
lab studies in cyanide poisoning show…
severe lactic acidosis in conjunction with a narrowing of the venous-arterial PO2 gradient, resulting from the inability of tissue to extract arterial oxygen
How do you treat cyanide poisoning?
admin of inhaled amyl nitrite which oxidizes ferrous iron (Fe2+) present in hemoglobin to ferric iron (Fe3+), generating methemoglobin
incapable of carrying oxygen but has high affinity for cyanide; binds and sequesters cyanide in the blood, freeing it from cytochrome oxidase and limiting its toxic effects
hydroxycobalamin (Vit B precursor) and sodium thiosulfate are also antidoes for cyanide poisoning
livedo reticularis, a blue toe, and acute kidney injury following coronary angiography
dx?
what is happening if invasive vascular procedures are preceding these events?
atheroembolic disease
can cause cholesterol containing debris from plaques to become dislodged from large arteries and show microemboli into circulation
What happens in systemic mastocytosis?
What are mutations often associated?
What are ssx?
clonal mast cell proliferation occurs in the bone marrow, skin and other organs
a/w mutations in the KIT receptor tyrosine kinase
cells are characterized by promient expression of mast cell tryptase; excessive histamine release mediates symptoms of syncope, flushing, hypotension, pruritis, and urticara (can also induce gastric acid secretions, leading to ulceration)
Tx for PCOS
advised on weight loss
OCPs if not wanting to be pregnant, to minimize endometrial proliferation, reduce androgenic symptoms
clomiphene or letrozole to induce ovulation if trying to become pregnant; clomiphene is a SERM that prevents negative FB inhibition on the HT and pituitary by circulating estrogen, resulting in increased FSH and LH production
What is the major cause of morbidity and mortality from theophylline intoxication?
seizures
tachyarrhythmias are other major concern
how do you treat theophylline intoxication?
admin of activated charcoal to reduce GI absorption
beta blockers for theophylline induced tachyarrhythmias
benzos and barbituates most effective against seizures
What upper midbrain structures mediate the direct and consensual pupillary light reflex?
optic nerve, pretectal nuclei, Edinger-Westphal nuclei, oculomotor nerve
What part of the spine will RA affect?
cervical spine
poison ivy reaction is mediated by what cells?
T cells; Type IV hypersensitivity reaction
in chronic heart failure, what initially offsets factors favoring edema?
increased lymphatic drainage
budding yeast with thick capsules - etiology?
what does this most commonly cause?
cryptococcus neoformans
meningoencephalitis is MC presentation; occurs in immunosuppressed pts and diagnosed by india ink staining of CSF;
cryptococcal pna dx’d by mucicarmine staining of lung tissue and bronchoalveolar washings
Reverse transcriptase polymerase chain reaction (RT-PCR) is used to detect and quantify levels of…
How would it be used to dx CML?
mRNA in a sample
by identifying an mRNA transcript containing both BCR and ABL exons in affected cells
In osteogenesis imperfecta, the defect in type 1 collagen results in impairment of what process?
osteoid production by osteoblasts
neurodegenerative disorder caused by accumulation of abnormally folded protein within the brain
Prio disease
What structure do prions normally exist in?
When does prion disease occur?
alpha-helical structure (PrP^c)
Prion disease occurs after a domain in this protein undergoes a conformation change from an alpha helix into beta-pleated sheet isoform (PrP^sc [scrapie]), which confers the ability to induce similar conformational changes in other proteins
What are qualities of the beta pleated sheets in prion disease?
resistant to proteases and forms long, highly neurotoxic fibrils, which accumulate intracellularly in neurons and form extracellular deposits
Why is there high chloride content in RBCs in venous blood?
CO2 is transported to lungs as bicarb
within RBCs, carbonic anhydrase forms bicarb from CO2 and water
excess bicarb is then transferred out of RBCs into the plasma via exchange with chloride ions
this exchange is known as “chloride shift”
What happens with pyruvate kinase deficiency?
causes hemolytic anemia due to failure of glycolysis and resultant failure to generate sufficient ATP to maintain erythrocyte structure
drugs that improve long term survival in patients with systolic HF
ACE-Is, AT II receptor blockers, aldosterone antagonists, beta blockers
What does isoproterenol do?
can mediate vasodilation via Beta2 receptors, particularly in striated muscle, renal, and mesenteric vascular beds, leading to decreased peripheral resistance with increased cardiac output
small and cuboidal in shape, grow in cords or sheets, and form follicle- or rosette-like structures (Call Exner bodies) that have a gland-like appearacne with a pink eosinophilic center and coffee bean nuclei
this is the histology consistent with…
what does this tumor secrete?
granulosa cell tumor
secretes estrogen
loss of palpable pulse during inspiration
pulsus paradoxus
cardiac tamponade
What factors inhibit renal calculi formation?
increased urinary citrate and high fluid intake
Epidermal growth factor receptor gene mutations are present in some …
non-small cell lung cancers, most commonly adenocarcinoma in nonsmokers
necolytic migratory erythema, an elevated painful and pruritic rash typically affecting the face, groin, and extremities; over time, small erythematous papules coalesce to form large, indurated plaques with a central clearing that often appears brown or bronze colored
dx?
glucagonoma
zinc deficiency mainly causes
erythematous skin lesions (mainly around body orifices) that are predominantly vesicular and pustular
other features include hypogonadism, impaired taste and smell, night blindness, and impaired wound healing
Pts with what IBD are more prone to developing fistulas/abscesses?
Crohn Disease
Activating mutations of KRAS gene lead to constitutive activation of
the EGFR pathway, promoting increased cell proliferation and growth
synchronization of glycogen degradation with skeletal muscle contraction occurs due to the release of
sarcoplasmic calcium following neuromuscular stimulation; increased intracellular calcium causes activation of phosphorylase kinase, stimulating glycogen phosphorylase to increase glycogenolysis
finely granular, diffusely homogeneous, pale eosinophilic cytoplasm (ground glass hepatocytes) are found in
hepatitis B infection
lymphoid aggregates within the portal tracts and focal areas of macrovesicular steatosis is seen in
hepatitis C infection
drug of choice for tx’ing bulemia nervosa
fluoxetine SSRI
urine leakage with coughing, lifting, or sneezing is going to be due to..
decreased urethral sphincter tone or urethral hypermobility
sudden overwhelming urge to urinate is a/w what dysfunction?
detrusor hyperactivity
What does phenylephrine do?
alpha 1 agonist that increases peripheral vascular resistance and systolic BP and decreases pulse pressure and HR
Polyarteritis nodosa (PAN) is a multisystem vasculitis characterized by episodic ischemic symptoms in various organs with sparing of the lungs; it is commonly associated with
Hepatitis B
Virtually all pts with polycythemia vera have a mutation in
JAK2, a non-receptor (cytoplasmic) tyrosine kinase associated with the erythropoietin receptor
What cells do infected macrophages with TB trigger?
triggers CD4 T lymphocytes to release IFNy, which leads to macrophage activation (improves intracellular killing ability) and differentiation into epithelioid histiocytes
child with proteinuria, hypoalbuminermia, and edema that are reversible with corticosteroids
dx?
minimal change disease
adult, severe coughing spells with vomiting occasionally, hasn’t seen a doc in years, clear CXR
dx
etiology
Pertussis
gram negative coccobacillus
Where are aconitase and enolase enzymes?
- aconitase is in the Krebs cycle, catalyzing the isomerization of citrate to isocitrate
- enolase is in glycolysis, catalyzing the conversion of 2-phosphoglycerate to phosphoenolpyruvate
In the absence of ADH, where is tubular fluid most concentrated?
most concentrated at the junction between the descending and ascendinng limbs of the loop of Henle and most dilute in the collecting tubules
what is the MC risk factor for calcium stones in adults?
hypercalciuria (most cases idiopathic)
pt will still be normocalcemia
infected fetus has severe anemia, heart failure, pleural effusions, pericardial effusions, and ascites
hydrops fetalis - probs from parvovirus infection
Where do NSAIDs affect the kidney?
they inhibit prostaglandin production which normally help maintain renal production by dilating the afferent arteriole, particularly in pts with intravascular volume depletion or CKD
inhibition of afferent dilation with NSAIDs results in reduced glomerular filtration and prerenal azotemia with elevations in creatinine and BUN (ratio >20:1)
What are the near-immediate effects of an ACE-I in someone with bilateral renal artery stenosis?
- lower AT II
- reducing systemic pressures and relative dilation of the efferent arteriole
- if bilateral RAS
- systemic pressure no longer high enough to overcome stenosis and renal blood flow drops
- dilation of efferent arteriole leads to a reduction of intraglomerular filtration pressure, which results in the reduction of GFR and filtration fraction
When would I see acanthocytes and how do they appear?
irregularly spced surface projections that vary in length and width
spur cells are the extreme form
typical of abetalipoproteinemia
When would you see spherocytes?
hereditary spherocytosis, autoimmune hemolytic anemia, burns, and blood samples that are not fresh
When do you see teardrop cells?
myelofibrosis
What are the G protein coupled receptors on pancreatic beta cells and what do they do?
- M3/Gq, Glucagon/Gs/q, B2/Gs, GLP-1/Gs
- increase insulin secretion
- A2 and somatostatin 2 Gi
- decrease insulin secretion
