UWorld 4 Flashcards
ARPCKD is caused by a mutation in PKHD1, the gene for….
where is this found?
deficiency leads to what?
fibrocystin
epithelial cells of both the renal tubule and bile ducts
deficiency leads to the characteristic polycystic dilation of both structures
To start the classic complement cascade, C1 binds to possibly what two things?
Which one is better at activating complement?
either two molecules of IgG or two molecules of IgM
IgM is better activator because it circulates in pentameric form
What are four classic features of nephrotic syndrome?
heavy proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia
what does low intravascular oncotic pressure stimulate in the liver?
stimulates increased lipoprotein production in the liver
What do you find on echo of hypertrophic cardiomyopathy?
- overall increase LV mass
- reduced LV cavity size
- asymmetric increase in LV wall thickness, predominantly affecting the septum
- normal or increased LV ejection fraction
- L atrial enlargement (secondary to increased LV end-diastolic pressure)
poorly developed coronary capillary network in hypertrophied regions of the heart with evidence of chronic ischemia
hypertrophic cardiomyopathy
fructose, glucose, and galactose can be detected by what test?
copper reduction test
aldolase B deficiency ssx?
tx?
life-threatening disorder caused by the inability to metabolize fructose-1-phosphate (toxic intermediate that accumulates in cells and depletes intracellular phosphate)
acutely symptomatic after ingestion of fructose containing foods and eventually develop liver failure
tx eliminate dietary fructose
autosomal recessive disorder caused by galactose-1-phosphate uridyl transferase deficiency
dx?
characteristics?
tx?
galactosemia
neonatal jaundice, vomiting, cataract formation, hepatomegaly, and failure to thrive
elimination of all milk products from diet and feeding with soy-based infant formula
essential fructosuria
ssx?
benign disorder, asymptomatic
urine will test positive for a reducing sugar due to the presence of unmetabolized fructose
What is the MC disorder of porphyrin synthesis?
Early and late deficiencies in the synthesis pathway result in what?
Porphyria cutanea tarda (PCT)
early - enzyme deficiencies cause abdominal pain and neuropsychiatric manifestations (due to metabolite build up) without photosensitivity
late - (following porphobilinogen [PBG] conversion) derangements cause photosensitivity, d/t accumulation of porphyrinogens that react with oxygen on excitation of UV light
What causes Porphyria cutanea tarda?
How would one get this disease?
uroporphyrinogen decarboxylase (UROD) deficiency
inherited or acquired (MC)
What happens to pressure and volume in LV if a traumatic AV shunt is created?
- blood under arterial pressure is allowed to directly enter the venous system
- increase preload by increasing the rate and volume of blood flow back to the heart
- increased diastolic filling
- higher end diastolic volume
- TPR is reduced because shunt is allowing bypass of arterioles
- decreasing afterload
What are the genetics a/w a minority of Down Syndrome patients?
unbalanced Robertsonian translocations
46 chromosomes with a translocation between 2 acrocentric nonhomologous chromosomes (eg, 46 XX t(14,21))
What is the difference between demyelinating neuropathies and axonal neuropathies?
- demyelinating neuropathy
- damage to myelin sheath
- loss of insulation results in delayed (or blocked) nerve conduction studies)
- axonal neuropathy
- damage to nerve axon
- loss of axon fibers results in reduced signal amplitude
What is the MCC of mononeuropathy?
focal nerve compression
results in nerve ischemia, leading to apoptosis of Schwann cells and localized demyelination
Why is decompensated heart failure a common cause of secondary mitral regurgitation?
- leads to an increase in LVEDV/preload
- with dilation of mitral valve annulus
- and taut stretching of chordae tendineae
- dilated annulus and restricted movement of the chordae tendineae can cause insufficient closure of an intrinsically normal mitral valve
- systemic HTN can also contribute to MR by favoring relatively lower-resistance regurg flow
What is the main toxin of C. perfringens?
aka?
What does it do?
lecithinase
phospholipase C or alpha toxin
catalyzes the splitting of phospholipid molecules; hydrolyzes lecithin containing lipoprotein complexes in cell membranes, causing cell lysis, tissue necrosis, and edema
C. perfringens uses what for energy?
How can this be demonstrated?
carbohydrates
rapid metabolism of tissue carbohydrates produces signifcant amounts of gas, which can be demonstrated radiographically by XR or CT
Throughout the cell cycle, what drugs work to inhibit completion? (anti-cancer drugs)
where do they act on the cell cycle?
- G1 - prepare building blocks of DNA synthesis
- G0 - rest phase
- S - DNA replication occurs
- topoisomerase I and II inhibitors (etoposide, irinotecan)
- antimetabolites (methotrexate, 5-FU)
- G2 - DNA checked for errors and make corrections if possible, if not then LOF mutations from apoptosis
- intercalating agents that create free radicals (bleomycin and doxorubicin)
- M - division occurs during this stage
- vinca alkaloids and taxanes
pain incurred during a migraine is due to activation of what?
trigeminal afferents that innervate the meninges
causes release of vasoactive neuropeptides, including substance P and calcitonin-gene related peptide (CGRP), results in neurogenic inflammation due to vasodilationa dn plasma protein extravasation
triptans MOA
serotonin agonists to directly counter the mechanism of migraines by inhibiting the release of vasoactive peptides, promoting vasoconstriction, blocking pathways in brainstem
trauma to the male pelvis would most likely cause injury to what part of the urethra?
What is the weakest portion of the posterior urethra?
When is anterior urethra more often damaged?
posterior urethra at the bulbomembranous junction
membranous urethra
anterior urethra MC damaged in straddle injuries
What are ssx of urethral injury?
- inability to void with a full bladder sensation
- high-riding boggy prostate
- blood at urethral meatus
especially with hx of pelvic fx
What is your major concern in a trauma pt with a known IgA deficiency?
How can you prevent this from occurring?
- IgE abs directed against IgA in host
- concern with blood products transfusion
- anaphylaxis d/t IgA in donor blood products
- wash blood products of residual plasma or receive from an IgA-deficient donor
formula for attributable risk percent in the exposed (ARPexp.)
= 100 x [(risk in exposed - risk in unexposed)/ risk in exposed]
What two vitamins does breast milk not have sufficient quantities of?
Vitamin D and K
AE of acyclovir that can be avoided?
acyclovir nephrotoxicity
acyclovir concentration in the collecting duct exceeds solubility, crystallization, crystalluria and renal tubular damage can occur
prevent with adequate hydration and reduction of rate infused
How does CO bind to heme?
competitively binds iron present in heme proteins
also capable of binding cardiac myoglobin with high affinity, disrupting hearts ability to use oxygen and thereby decreasing CO
Statins, when combined with what other drug can cause myopathy and rhabdo?
how?
statins metabolized by P450 3A4 (except pravastatin)
concomitant admin of drugs that inhibit statin metaboism (macrolides) increases AE risk
azithro doesnt have significant effect
The metanephric mesoderm in the embryonic kidney give rise to what structures?
golmeruli, Bowman’s space, proximal tubules, the loop of henle, and distal convoluted tubules
How would Crohn disease result in abnormal bruising?
- Crohn often involves terminal ileum
- terminal ileum is where bile acids are reabsorbed
- due to inflammation the bile acids are not reabsorbed
- deficiency in fat soluble Vitamens ADEK
- Vitamin K deficiency results in easy bruising, hemarthrosis after minor trauma, and prolonged bleeding after surgery
- deficiency in fat soluble Vitamens ADEK
- due to inflammation the bile acids are not reabsorbed
- terminal ileum is where bile acids are reabsorbed
What are early adaptive changes in the kidney with diabetic nephropathy?
- increase GFR due to
- increase Na resorption in the PCT by Na-glucose cotransporter
- decreased Na and fluid devlivery to macula densa
- activation of tubuloglomerular autoregulation system
- dilation of afferent arterioles and constriction of efferent
- increase GFR and glomerular hypertrophy
- dilation of afferent arterioles and constriction of efferent
- activation of tubuloglomerular autoregulation system
- decreased Na and fluid devlivery to macula densa
- increase Na resorption in the PCT by Na-glucose cotransporter
autosomal recessive metbaolic disorder caused by inactivating mutations affecting the neurtral amino acid transporter
dx?
what does this result in?
Hartnup disease
impaired transport of neutral aa, esp tryptophan, in small intestine and proximal tubule of kidney
tryptophan is an essential aa and a precursor for what substances?
why is this important?
niacin, serotonin, and melatonin
conversion of tryptophan to niacin is responsible for the generation of up to half of the NAD+ required for redox reactions
ssx of Hartnup disease?
dx confirmation?
tx?
intermittent attacks of pellegra-like skin eruptions and cerebellar ataxia in early childhood that become less severe with age
detect excessive amounts of neutral amino acids in the urine (neutral aminouria)
high protein diet with daily niacin or nicotinamide supplementation
pleural effusions due to pressure changes are typically…
common causes include…
transudate
HF, cirrhosis, nephrotic syndrome
What is Light criteria?
Exudate criteria:
- fluid protein:serum protein >0.5
- fluid LDH:serum LDH >0.6
- fluid LDH > 2/3 ULN serum LDH
What is the best method for determining whether a gene is being expressed is to
analyze for the presence of mRNA using a Northern blot
epigastric calcifications and hx of alcohol abuse
dx?
how do calcifications come about?
chronic alcoholic pancreatitis
- alcohol induces secretion of protein rich fluid
- proteinaceous secretions precipitate in pancreatic ducts
- form ductal plugs that may calcify and can be detectable on abdominal imaging
- proteinaceous secretions precipitate in pancreatic ducts
what might pancreatic exocrine insufficiency lead to?
(eg failure to secrete amylases, proteases, and lipases)
leads to malabsorption with consequent dirrhea/steatorrhea, weight loss and bulky, frothy stools
roundworm transmitted by misquitos and causes lymphatic infection; blood smear shows long, thin microfilaria in circulation
wuchereria bancrofti
How do nitrites cause poisoning?
inducing conversion of this heme iron to the oxidized ferric (Fe3+) state, leading to the formation of methemoglobin
what causes typical atrial flutter?
what area needs to be ablated in treatment?
large reentrant circuit that traverse the cavotricuspid isthmus
region of right atrial tissue between the IVC and the tricuspid valve annulus
an accessory pathway that bypasses the AV node is present in…
what is indicative of this on EKG?
AV reentrant tachycardia aka Wolf-Parkinson-White syndrome
delta wave
what is homocysteine and why is it elevated in folate deficiency?
amino acid associated with endothelial cell injury and vascular inflammation
levels are elevated in folate deficiency due to impaired conversion into methionine
how does folate deficiency affect DNA synthesis?
inhibits synthesis of nucleic acids, specifically dTMP;
leads to defective DNA synthesis that causes increased apoptosis of hemopoietic cells and megaloblastic anemia
what is the MCC of spinal stenosis and what does this result in?
degenerative arthritis of the spine
results in narrowing of teh spinal canal due to intervertebral disc herniation, ligamentum flavum hypertrophy, and osteophyte formation affecting the facet joints
What are 5 major toxicities of Amp B?
- acute infusion-related reactions
- dose-dependent nephrotoxicity
- electrolyte abnls (hypoMg and hypoK)
- anemia (suppression of EPO syn)
- thrombophlebitis (at injection site)
macrocyclic abx that inhibits the sigma subunit of RNA polymerase, leading to protein synthesis impairment and cell death
rx?
what does this tx?
Fidaxomicin
C diff
celecoxib selectively inhibits
COX 2
What do Fas receptors do?
initiate the extrinsic pathway of apoptosis through a cytoplasmic component known as the death domain
bind FasL, receptor trimerizes, allowing their death domains to forma binding site for an adapter protein called FADD (Fas-associated death domain)
receptor bound FADD stimulates the activation of initiator caspases (8 and 10) that begin an activation cascade culminating the activation of executioner caspases (3 and 6)
initiate terminal processes of apoptosis, including cleavage of DNA, fragmentation of the nucleus, orgnaelle autodigestion, and plasma membrane blebbing
Fas receptor is expressed on T cells. Once activated, T cells begin to express FasL, which can bind on same or another cell.
During initial clonal expansions, activated T cells are resistant to Fas-induced apoptosis, but become more sensitive with progressive stimulation.
What happens then?
What occurs if this is not functioning?
in constant presence of stimulating self-antigens, activated T cells eventually undergo apoptosis in process known as activation-induced cell death
without this, autoreactive T cells would be rampant and result in autoimmune diseases
What is T cell anergy?
state of prolonged unresponsiveness that occurs in T lymphocytes as a form of immune tolerance
occurs when self-reactive T cells bind MHC molecules without receiving the needed costimulatory signal (binding of CD28 on T cells with the B7 on antigen-presenting cells)
What cytokines induce Th1 and Th2 formation?
IFNy and IL-2 induce Th1 formation
IL-4 stimulates Th2 development
What are inducers of Cytochrome P450?
Chronic alcoholics steal phen-phen and never refuse greasy carbs
- chronic alcoholic
- St. John’s wart
- phenytoin
- phenobarbital
- nevirapine
- rifampin
- griseofulvin
- carbamazepine
What are inhibitors of Cytochrome P450?
SICKFACES.COM
- sodium valproate
- isoniazid
- cimetidine
- ketoconazole
- fluconazole
- acute alcohol abuse
- chloramphenicol
- erythromycin (macrolides)
- sulfonamides
- ciprofloxacin
- omeprazole
- metronidazole
Substrates of CYP450?
Always Think When Outdoors
- anti-epileptics
- theophylline
- warfarin
- OCPs
Common sulfa drugs
- sulfonamide abxs
- sulfasalazine
- probenecid
- furosemide
- acetazolamide
- celecoxib
- thiazides
- sulfonylureas
amyloid light chain amyloidosis is associated with what bone marrow aspirate findings?
multiple myeloma and other monoclonal plasma cell dyscrasias due to the deposition of insoluble Ig light chain fibrils in major organs
a bone marrow sample with greater than 10% plasma cells is strongly suggestive of multiple myeloma
pt presents with esophogeal dysmotility, telangiectasias, and ulcers on her fingers
dx?
CREST syndrome
what is the pathogenesis of temporal arteritis?
cell mediated immunity - inflammatory infiltrate in infected vessels is composed of lymphocytes (predominantly CD4 T cells) and macrophages, often with multinucleated giant cells
production of cytokines, esp IL-6 appears to closely correlate with severity of disease
How do you treat temporal arteritis/giant cell arteritis?
mab v IL-6 (tocilizumab)
Antibodies to what are associated with pathogenesis of ANCA associated vasculitides?
antibodies to myeloperoxidase and proteinase-3
cytokine belonging to the tumor necrosis factor ligand family?
inadequate levels of this will lead to …
whereas excess …
BAFF - B cell Activating Factor
deficient: lead to immunodeficiency
excess: cause autoimmune diseases (SLE)
defect in linea albo and presents as protrusions at the umbilicus
prognosis?
a/w?
umbilical hernia
soft, reducible, benign
Down Syndrome
Pts with medically intractable symptoms of Parkinsons can consider DBS of what structures?
How does this work?
globus pallidus internus or subthalamic nucleus
promotes thalamo-cortical disinhibition with improved mobility
What arises from the third pharyngeal pouch?
thymus and inferior parathyroid glands
most laryngeal cartilages develop from what?
4th and 6th pharyngeal arches
What are protective measures that decrease the frequency of ovulation and decrease risk of epithelial ovarian cancer?
What are RF for epithelial ovarian cancer?
oral contraceptives, multiparity, and breastfeeding
BRCA mutation, nulliparity, and infertility
What is calcineurin and what does it do?
What inhibits calcineurin?
protein phosphatase in normal T cells
once activated it dephosphorylates nuclear factor of activated T cells (NFAT) which allows NFAT to enter the nucleus and bind to IL-2 promoter
stimulates growth and differentiation of T cells
Cyclosporine and tacrolimus (immunosuppressants)
tumor suppressor protein encoded by the NF1 gene on chromosome 17
what does this do?
neurofibromin
protect against cancer as it is a key suppressor of Ras, one of the more powerful activators of cell growth and proliferation
What are the differences between false and true diverticula? Give examples of each.
- false diverticulum
- contain only mucosa and submucosa
- layers herniate through defects of the muscular layer
- eg colonic and Zenker diverticula
- true diverticulum
- all three parts of the wall - mucosa, submucosa, and muscularis
- contains ectpoic mucosa too (gastric or pancreatic MC)
- Meckel’s
defects in ApoE3 and ApoE4, leading to decreased clearance of chylomicrons and VLDL remnants
dx?
what labs will be elevated?
familial dysbetalipoproteinemia (type III hyperlipoproteinemia)
cholesterol and and triglycerides
What characterizes chronic lung transplant rejection?
what will this lead to?
submucosal lymphocytic inflammation in the walls of the small airways
ingrowth of granulation tissue into the lumen leads to airway obstruction and obliteration (bronchiolitis obliterans)
What is the pathophysiology of hyperacute lung transplant rejection?
preformed host antibodies to donor ABO or HLA
neutrophilic infiltration with fibrinoid necrosis and thrombosis
What is the pathophysiology to acute lung transplant rejection?
cell mediated response to mismatched donor HLA
perivascular (small lung vessels) and submucosal (bronchiole) lymphocytic infiltrates
nuclear transcription factors that directly bind DNA via a leucine zipper motif
what kind of genes code for these?
c-Jun and c-Fos
proto-oncogenes
homodimeric calcium-binding proteins, similar in structure to calmodulin and important in intracellular functions such as protein phosphorylation and cell growth and differentiation
what is this a marker for?
S-100
marker for cells of neural crest derivation (melanocytes and Schwann cells), as well as Langerhans cells and other dendritic cells
What does southwestern blotting detect?
DNA-binding proteins such as transcription factors, nucleases, and histones
Where does deoxygenated blood come from when circulation is about to go into the L atrium?
pulmonary veins from bronchial circulation and thesbian veins
What is the mechanism of sodium nitroprusside on the heart?
short acting agent that causes balanced vasodilation of the veins and arteriesl;
decreases LV preload and afterload, allowing maintenance of CO (no change to SV) at a lower LV pressure
LV contractility unchanged
What runs through the hepatoduodenal ligament?
portal triad (hepatic artery, portal vein, common bile duct)
During inflammation, what causes COX-2 upregulation?
infiltrating cells that secrete cytokines IL-1 and TNFa
What is the MOA of colchicine?
binds to tubulin, which inhibits microtubule formation. results in impaired neutrophil mitosis and decreased neutrophil chemotaxis
What is the major virulence factor of Haemophilus influnezae type b?
polyribosylribitol phosphate- capsule component
(polysaccharide capsule)
What is in the cell wall of Staph aureus that helps prevent opsonization by binding the Fc region of immunoglobulins?
Protein A
What is a major cell wall component and major virulence factor of Mycobacterium tuberculosis that protects it from being killed by macrophages and stimulates granuloma formation?
trehalose dimycolate
pt with membranous nephropathy, flank pain, hematuria, and L varicocele
dx? due to?
renal vein thrombosis due to nephrotic syndrome
Nephrotic syndrome is a hypercoagulable state. This can lead to renal vein thrombosis - why is that?
due to increased glomerular capillary wall permeability in nephrotic syndrome, many important substances are lost in the urine;
loss of anticoagulant factors, esp antithrombin III, leads to the hypercoagulable state, of which RVT is a manifestation
What would symptoms of sudden onsent renal vein thrombosis be?
sudden onset abdominal or flank pain, gross hematuria, with elevated LDH as a result of renal infarction
MOA of flutamide?
indication?
nonsteroid anti-androgen that acts as a competitive inhibitor of testosterone receptors; used in combo with long-acting gonadotropin-releasing hormone agonists for the tx of prostate cancer
exogenous corticosteroid use will inhibit what? What lab values does this lead to?
what does long term suppression lead to?
is anything spared?
sudden cessation of glucocorticoids can cause what?
inhibits entire HT-pituitary-adrenal axis
low levels of CRH, ACTH, and endogenous cortisol
leads to adrenocortical atrophy
zona glomerulosa spared bc AT II is primary trophic hormone
precipitate adrenocortical insufficiency and adrenal crisis
what is the primary goal of the thiazolidinedione medication calss?
what are important genes upregulated by these drugs?
what do they do to blood triglyceride level?
decrease insulin resistance
upregulate GLUT4 and adiponectin
lower blood triglycerides
Sideroblastic anemia dx’d by bone marrrow aspirate with Prussian blue stain - What are causes of sideroblastic anemia?
- X linked sideroblastic anemia
- due to an delta-aminolevulinate synthase mutation
- myelodysplastic syndrome
- alcohol abuse
- copper deficiency
- certain meds
- isoniazid, chloramphenicol, linezolid
Isoniazid directly inhibits what?
what does this normally do?
the enzyme pyridoxine phosphokinase, which normally converts pyridoxine (B6) to active form pyridoxal 5’ phosphate
What does pyridoxal 5’ phosphate a cofactor for? why is this important?
What does inhibition of this cause?
for delta-aminolevulinic acid (ALA) synthase
the enzyme that catalyzes the rate limiting step of heme synthesis
microcytic, hypochromic anemia
The ischemic bowel undergoes anaerboic metabolism, causing….. in the blood that leads to……
this stimulates ……., a process by which renal epithelial cells metabolize …., generating ammonium and bicarb.
lactate accumulation
anion gap metabolic acidosis
renal ammoniagenesis
glutamine
What is the end result of the process to buffer acids in the blood?
ammonium ions are transported into the tubular fluid and excreted in urine while peritubular capillaries absorb bicarb, which functions to buffer acids in the blood
what is most useful initial test for confirming carcinoid syndrome?
increased level of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in a 24 hour urine sample
why do carcinoid tumors in the intestine not cause carcinoid syndrome?
their secretory products are metabolized by the liver before entering systemic circulation
In Cushing syndrome due to an ACTH-secreting pituitary adenoma you will see…
ACTH is high and cortisol production can be suppressed by high-dose dexamethasone
In pts with ectopic ACTH production, what can happen with cortisol and ACTH?
cortisol and ACTH production are not suppressed by low or high dose dexamethasone
In normal individuals, low dose dexamethasone will…
what is the dx if this does not happen?
suppress ACTH and cortisol levels through negative feedback
endogenous Cushing syndrome
Major AE of nitroprusside?
How would you correct/tx this?
cyanide toxicity
- direct binding of cyanide ions
- hydroxocobalamin
- induction of methhemoglobinemia
- sodium nitrite
- use of detoxifying sulfur donors
- sodium thiosulfate
symptoms of LE claudication (pain and cramping with exercise), BP discrepancy between UE and LEs, and delayed or diminished femoral pulses - dx?
why would continuous murmurs and pulsatile intercostal collaterals develop?
coarctation of aorta
secondary to restricted circulation
spinocerebellar degeneration with predominantly spinal ataxia; produces difficulty walking, a/w hypertrophic cardiomyopathy
Friederich ataxia
What drug is a nucleoside monophosphate (ie a nucleotide) that requires only cellular kinases for activation?
cidofovir
in prospective studies, disproportionate loss to follow-up between the exposed and unexposed groups creates potential for what kind of bias?
attrition bias, a form of selection bias
What is the MC GI complication in Down Syndrome pts?
how is this recognized?
duodenal atresia
failure of recanalization of the duodenum in early gestation; infants present during the first few days of life with bilious emesis and the classic “double-bubble” sign, which represents the dilated stomach and proximal duodenum
What are GI complications often seen in Down syndrome pts?
- duodenal atresisa
- imperforate anus
- Hirschsprung disease
- tracheoesophageal fistula
- celiac disease
what type of cells have abundant basophilic cytoplasm, perinuclear paleness (large Golgi apparatus), and nuclei with “clock-face” chromatin?
more than 10% of these cells in bone marrow raises suspiscion of…
plasma cells
multiple myeloma
What measurement increases in COPD pts?
residual volume:total lung capactiy ratio
higher FRC
What causes a L shift on oxygen-hemoglobin dissociation curve?
- decreased H+ (increased pH)
- decreased 2,3- BPG
- decreased temperature
What causes a R shift on oxygen-hemoglobin curve?
- increased H+ (decreased pH)
- increased 2,3-BPG
- increased temp
What does an aspirate of reactive arthritis joint show?
sterile due to deposition of immune complexes
What are the parts of a normal jugular venous pulse wave tracing?
- R atrial contraction (a)
- bulging of tricuspid valve during RV contraction (c)
- R atrial relaxation (x)
- continued inflow of venous blood (v)
- passive emptying of RA after tricuspid valve opening (y)
constrictive pericarditis on CT will show…
calcification and thickening of the pericardium
nasal hemianopnia would have a lesion where?
what is this often due to?
ipisilateral peri-chiasmal
calcification or aneurysm of the ICA impinging on uncrossed, lateral retinal fibers
When does hemoglobin S aggregate?
in the deoxygenated starte;
HbS polymers form fibrous strands that reduce RBC membrane flexibility and promote sickling
sickling occurs under conditions with anoxia including low pH and high levels of 2,3 BPG
What are the class III antiarrhythmics and what is their MOA?
amiodarone, sotalol, dofetilide
block K+ channels and inhibit the outward K+ currents during phase 3 of the cardiac action potential, prolonging repolarization and total action potential duration
what is myelopathy associated with vit B12 deficiency?
- subacute combined degeneration
- myelin degeneration of both ascending (dorsal columns) and descending (corticospinal tract) pathways
- loss of position and vibration sensation, sensory ataxia, and spastic paresis are common manifestations
What artery supplies the inferior wall of the heart?
posterior descending artery, which in 90% of pts comes from the right coronary artery
How do I calculate the absolute risk increase?
take the adverse event rate in each group and find the difference
What is seen on gross exam and light microscopy of glioblastoma multiforme?
areas of necrosis and hemorrhage are seen on gross exam; light microscopy shows pseudopalisading tumor cells around areas of necrosis
FSH stimulates the release of what hormone from what cells in males?
release of inhibin B from Sertoli cells in the seminiferous tubules
What does galactosemia in an infant present as?
vomiting and lethargy soon after initiating breast feeding;
in GALT (galactose-1-phosphate uridyl transferase) deficiency, toxicity of accumulated galactose-1-phosphate is responsible for impaired liver function and renal dysfunction
pts are aslo predisposed to E. coli sepsis
What receptors act directly as transcription factors and contain zinc-finger binding domains?
intracellular receptors that bind steroids, thyroid hormone, amd fat-soluble vitamins
What are zinc finger motifs composed of?
chains of amino acids bound together around a zinc atom via linkages with cysteine and histadine residues
What are classic PE findings of a pt with a hx of rheumatic fever?
- loud first heart sound (S1)
- an early diastolic high frequency opening snap after S2
- low pitched diastolic rumble
findings best heart at cardiac apex using bell of stethoscope with pt lying on the L side in held expiration
Why is atropine indicated in bradycardia? What is a common AE?
decreases vagal influence on the SA and AV nodes as an anticholinergic
AE: increased IOP, ppt acute close-angle glaucoma in some
Second gen antipsychotics MOA
dopamine receptor antagonist
serotonin 5-HT2A receptor antagonist
Clinical findings in serum sickness?
what can ppt this?
fever, pruritic skin rash, arthralgias, and low serum C3 and C4 complement levels
reaction to nonhuman proteins characterized by vasculitis resulting from tissue deposition of circulating immune complexes – chimeric monoclonal antibodies or nonhuman immunoglobulins
What is the MOA of hydroxyurea in the treatment of sickle cell anemia?
increases Hb F synthesis
increased percentage of Hb F confers protection against the polymerization of sickle cells
What do Gardos channel blockers do?
calcium-dependent (Gardos) potassium channel regulates the transport of K+ and water through the red blood cell membrane - when blocked K+ and water efflux is reduced, preventing dehydration of RBCs and reducing the polymerization of Hb S
Cholinergic crisis and myasthenic crisis present similarly, how do you tell the difference?
- myasthenic crisis is due to the pt being undertx’d
- not enough ACh in NMJ
- tx with edrophonium (Tensilon test) increases NM transmission and provides temporary improvement
- increase pyridostigmine dose
- cholinergic crisis
- too much AChE inhibitor and excess ACh
- NMJ becomes insensitive to ACh so edrophonium will not relieve ssx
- temporarily discontinue edrophonium
erythematous, itchy breast rash with skin texture changes analogous to an orange peel —
this is the key feature of…
caused by…
peau d’orange
inflammatory breast cancer
cancerous cells obstructing lymphatic drainage due to spread to the dermal lymphatic spaces
process by which only T cells expressing a TCR that is able to bind self MHC is allowed to survive
where does this occur?
what does it involve?
Positive Selection
thymic cortex
involves interaction of T cells with thymic cortical epithelial cells expressing self MHC
process by which T cells possessing TCRs that bind with high affinity to self antigen or self MHC class I or II are eliminated by apoptosis
where does this occur?
what does it involve?
negative selection
thymic medulla
involves interaction of developing T cells with thymic medullary epithelial and dendritic cells
a distinguishing feature of this disease is cytosolic accumulation of glycogen with abnormally short outer chains (limit dextrins)
Cori disease (debranching enzyme deficiency)
Cori disease presents with…
in infancy or childhood with hypoglycemia, ketoacidosis, hepatomegaly, and muscle weakness and hypotonia
How does brown fat in babies produce heat?
uncoupling oxidative phosphorylation with the protein themogenin
given phenotypically normal parents, the probability that a female sibiling of a male affected by an X linked recessive disease will give birth to an affected child is …
1/8
How does CKD affect parathyroid hormone?
- CKD causes hyperphosphatemia d/t impaired ability of the kidneys to excrete phosphorus
- triggers release of Fibroblast GF 23 from bone
- lowers calcitriol ( 1,25) production and intestinal calcium absorption
- CKD causes decreased renal conversion of 25 to 1,25
- hypocalcemia and hyperphosphatemia stimulates secretion of PTH
- secondary hyperparathyroidism
intestinal atresias of the midgut are due to…
what happens and what might this result in?
vascular occlusion in utero
decreased perfusion leads to ischemia of bowel segment, subsequent stenosis or atresia of the lumen
can result in distal segment of ileum assuming a spiral configuration around an ileocolic vessel (apple-peel or Christmas tree deformity)
flecainade drug info
Class IC antiarrhythmic
Na channel blocer that have increased effect at faster heart rate (use-dependence)
more effective at tx’ing tachy arrhythmias, can also cause prolonges QRS duration (proarrhythmic effect) at higher HR
Calculation for NNT
NNT = 1 / ARR
absolute risk reduction = control event rate - experimental event rate
If a heart is left dominant, what is the artery that will feed the PDA?
What does this artery supply?
left circumflex feeds PDA
PDA supplioes the AV node via AV nodal artery
night blindness associated with thickened, dry skin
deficiency in what?
why would someone in the developed world appear to have this deficiency?
vitamin A deficiency
from malabsorption related to biliary obstruction, exocrine pancreatic insufficiency or small-bowel resection (Crohn disease or bariatric sx)
autoimmune disease characterized by destruction of small bile ducts in the liver
primary biliary cholangiitis
What is the pathogenic mechanism for Shigella infection?
mucosal invasion, particulary via the M cells that overlie Peyers patches
lyse containment vacuole and enter cytosolic compartment
induces apoptosis of the host cell and spread to adhacent cells via protrusions created through host-cell actin polymerization
how do you prevent the development of glandular breast tissue in males who are taking androgen deprivation therapy for prostate cancer?
tamoxifen inhibits the effect of estrogen on breast tissue and can reduce gynecomastia
PPV formula
TP/ (TP +FP)
cytosine methylation is used in …
a phenomenon in which an offspring’s genes are expressed in a parent-specific manner
eg?
genomic imprinting
allele inherited from the father may be inactivated or “imprinted” by methylation so that only the allele from mom is expressed
What receptors mediate arterial vasoconstriction and vasodilation?
alpha 1 do vasoconstriction and B2 do vasodilation
condition results in recurrent bacterial and fungal infections due to impaired intracellular killing by phagocytes?
what is the genetic defect in?
chronic granulomatous disease
NADPH oxidase complex
what kind of bacteria and fungi are reinfecting during CGD?
abx for lung abscess
Clindamycin to cover anaerobic and aerobic
incomplete fusion of the urethral folds in males results in…
hypospadias - abnormal opening of the urethra proximal to the glans penis along the ventral shaft of the penis
Replication of the Hep B genome occurs where and how?
within a newly synthesized capsid through the action of RT on an RNA template;
mature caspid contains partially ds circular DNA and RT
pt presents with skeletal abnormalities, lens dislocation, intellectual deficits, vascular thromboses, and a genetic defect in the cystathionine beta synthase enzyme
dx?
why does this happen?
homocystinuria
single genetic defect creating multiple seemingly unrelated phenotypic manifestations, is pleiotropy
phenomenon whereby gametogenesis within the parent organism results in the separation of paired alleles so that each offspring inherits only half of each parents genetic composition
law of segregation (Mendel’s first law)
ability of one disease or trait to be caused by mutations in multiple different genes
ex?
locus heterogeneity
familial hypercholesterolemia
How can you differentiate between pancreatic and mucosal causes of malabsorption?
D-xylose test - monosaccharide whose absorption is not affected by exocrine pancreatic insufficiency
D-xylose test will be normal with pancreatic damage
What is the most sensitive strategy for screening for malabsorptive disorders?
test stool for fat with Sudan III stain - fat is typically the most severely affected macronutrient in generalized malabsorption
In X linked recessive inheritence, if there is an affected father then…
all daughters are carriers and all sons are normal
In X linked recessive, if mother is a carrier then
daughters have a 50% chance of being a carrier and sons have a 50% chance of being affected
In rapidly progressive glomerulonephritis with no immunoglobulin or complement deposits on the basement membrane, the dx is…
they will have elevated serum titers of…
Pauci-immune RPGN
antineutrophil cytoplasmic abs (ANCA)
When does loss of cardiomyocyte contractility occur after the onset of total ischemia?
At what point does ischemia become irreversible?
If it lasts less than this time, what is this called?
within 60 seconds
30 minutes ischemia becomes irreversible
myocardial stunning
impaired transport of ornithine into mitochondria can be caused by ornithine translocase deficiency, which results in a defect in the …
hepatic urea cycle
What does the urea cycle do?
converts ammonia, generated from catabolism of amino acids, into urea for excretion in the urine
Urea cycle defects cause accumulation of ammonia and what ssx?
progressive lethargy, vomiting, seizures, and cerebral edema (hyperreflexia and abnormal posturing when severe) in infancy and early childhood
What is the main tx for urea cycle disorders?
protein restriction - body receives essential amino acids needed for growth and development but not in excess such that excessive ammonia is formed
restriction of branched chain amino acids (valine, leucine, isoleucine) is used to treat
maple syrup urine disease and propionic acidemia
A phenylalanine-free diet is recommended in patients with
phenylketonuria (phenylalanine hydroxylase deficiency)
What can be used to treat homocystinuria?
Pyridoxine (Vit B6)
What does the contractile mechanism in skeletal muscle depend on?
proteins - myosin II, actin, tropomyosin, and troponin - along with calcium ions
Lamotrigine indication and AE
anticonvulsant mood stabilizer, effective in the depressed phase of bipolar and used in maintenance phase;
a/w risk of benign rash progressing to SJS
How is isoniazid metabolized?
acetylation to N-acetyl-isoniazid in hepatic microsomal system by N-acetyl transferase and is subsequently excreted in the urine
Slow acetylators will cause accumulation of what drugs?
isoniazid, dapsone, hydralazine, and procainamide
What causes acute tubular necrosis with vacuolar degeneration and ballooning of the proximal tubular cells?
What are typical clinical findings?
ethylene glycol ingestion
altered mentation, renal failure, high anion gap metabolic acidosis, increased osmolar gap, and calcium oxalate crystals in the urine
What causes light chain cast nephropathy due to obstruction of the proximal tubules?
multiple myeloma
biopsy shows eosinophilic (light-chain) casts
a/w hypercalcemia and anemia
How can AAT deficiency by demonstrated?
reddish-pink globules on periodic acid-Schiff stain; globules represent unsecreted, polymerized AAT in the periportal hepatocytes
What is tumor lysis syndrome characterized by?
hyperphosphatemia, hypocalcemia, hyperkalemia, and hyperuricemia
What are the initial steps of gluconeogenesis?
conversion of pyruvate to oxaloacetate and oxaloacetate to phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase, respectively
Neuro ssx in anemic pt - need to tx with
vit B12
What would you see in lymph node strongly indicative of malignancy?
monoclonal lymphocytic proliferation
What antiemetic drugs work at the NK1 receptor as antagonists?
Aprepitant and fosaprepitant
Disease management of pyruvate dehydrogenase deficiency includs changing to a…
ketogenic diet
What are exclusively ketogenic amino acids? What does this mean?
lysine and leucine
they cannot be metabolized to pyruvate and consumption will not lead to increased production of lactic acid
Malabsorption in celiac disease can lead to what vitamin deficiency? What labs are found with this?
Vit D deficiency
hypophosphatemia, hyperparathyroidism, hypocalcemia or normal calcium
How does unilateral renal artery stenosis affect the kidneys?
causes hypoperfusion and activation of RAAS; AT II causes arteriolar vasoconstriction and increases aldosterone and ADH synthesis
resultant hypertension helps reduce the decline in GFR in affected kidney, but causes a pressure natriuresis with increased sodium excretion in the unaffected kidney
How do Sertoli cells aid in generation of reproductive organs?
- Sertoli cells suppress female internal reproductive organ development by producing anti-Mullerian hormone
- Mullerian duct involution
- produce androgen binding protein, which concentrates testosterone in the seminiferous tubules to enable spermatogenesis
How do Leydig cells aid in creation of reproductive organs?
- secrete testosterone, which stimulates Wolffian (mesonephric) ducts to develop into internal male productive organs
- epididymides, vas deferens, ejaculatory ducts, seminal vesicles
- testosterone is peripheral converted to DHT, which transforms the genital tubercle, urogenital folds, and labioscrotal swelling into the external male reproductive organs
What happens in embryological development without Sertoli cells?
Mullerian ducts develop into the internal female reproductive organs
Leydig cells still cause development of internal and external reproductive organs
MCC of hirsutism? a/w?
tx?
PCOS a/w elevated androgen levels
combination OCPs are usually the first choice - they suppress LH secretion from the pit, decreasing ovarian androgen production; also increase SHBG by the liver, decreasing free testosterone levels
In the presence of ADH, what is the most concentrated fluid in the nephron?
most dilute?
collecting ducts
thick ascending limb of loop of henle and DCT contain the most dilute fluid
MOA of colchicine?
inhibits tubulin polymerization and microtubule formation in leukocytes, reducing neutrophil chemotaxis and emigration to sites inflamed by tissue deposition of monosodium urate crystals
AE of colchicine?
diarrhea, nausea, vomiting, abdominal pain
Pretreatment with what drug can eliminate the beta effects of epinephrine (vasodilation and tachycardia) leaving only the alpha effect (vasoconstriction)
Propanolol or other nonselective beta antagonist
a process whereby the exons of the pre-mRNA produced by transcription of a gene are reconnected in multiple ways during post-transcriptional processing
what does this allow?
alternative splicing
creates different mRNA sequences and subsequently, different protein isoforms - increases biodiversity of proteins encoded by the genome
