UWorld 3 Flashcards
lesions in the glossopharyngeal nerve would cause what?
loss of sensation in the upper pharynx, posterior tongue, tonsils, and middle ear cavity, loss of taste sensation in posterior 1/3 tongue, afferent part of gag reflex
symptoms of infants with hydrocephalus?
why do the latter two occur?
- macrocephaly, poor feeding, muscle hypertonicity, and hyperreflexia
- hypertonicity and hyperreflexia result from UMN injury caused by stretching of the periventricular pyramidal tracts
elevated transaminases and low serum ceruloplasmin
dx?
tx?
Wilson disease
D-penicillamine (has free sulfhydryl group working as copper chelator)
thyamine deficiency can be diagnosed if baseline…. is low, but increases after addition of thiamine pyrophosphate
erythrocyte transketolase activity
What are three enzymes that use thiamine as a cofactor?
pyruvate dehydrogenase
alpha-ketoglutarate
transketolase
What are the MC adeverse effects of volatile anesthetic agents?
- increased cerebral blood flow causing increased
ICP - myocardial depression
- hypotension
- respiratory depression
- decreased renal function
MC AE of phenytoin?
how does this happen?
gingival hyperplasia
rx causes increased expression of platelet-derived growth factor (PDGF); when gingival macrophages are exposed to increased amounts of PDGF, they stimulate proliferation of gingival cells and alveolar bone
urea cycle enzyme that produces urea and ornithin from arginine?
deficiency of this causes what?
tx?
arginase
results in progressive spastic diplegia, growth delay, and abnormal movements
arginine free, low protein diet
atrophy of the caudate nuclei with enlargement of the lateral ventricles
huntington disease
virulence factor of Neisseria meningitidis to initially attach to and colonize the nasopharyngeal epithelial surface
what makes this difficult to target with a vaccine?
pili
they undergo significant antigenic variation
what is the measure of potentcy of an inhaled anesthetic?
MAC - minimal alveolar concentration
concentration of the anesthetic in the alveoli that renders 50% of pts unresponsive to painful stimuli
the lower the MAC, the more potent the anesthetic
tx for HSV encephalitis and MOA
IV acyclovir
nucleoside analog that, once activated, competes with deoxyguanosine triphosphate for viral DNA polymerase
ultimately halts viral DNA synthesis
in mitochondrial diseases, offspring of males and females are affected equally, but there are variable degrees of severity.
why?
during mitosis, mitochondria are randomly distributed between daughter cells
some cells contain mito with mostly damaged and others with mostly normal
mix of the two types is called heteroplasmy
what mitochondrial syndrome leads to bilateral vision loss?
Leber hereditary optic neuropathy
myoclonic seizures adn myopathy associated with exercise. skeletal muscle biopsy shows irregularly shaped muscle fibers
myoclonic epilepsy with ragged-red fibers
mitochondrial disease
hx of sz disorder, now having stroke like episodes with residual neuro deficit; also soffers from muscle weakness; blood test show increased serum lactate levels both post exercise and at rest
mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
MELAS
Where would a marcus gunn pupil have a lesion?
CL optic tract
a bacteria with extended-spectrum beta lactamase means what?
what is my drug of choice?
they can inactivate even more abx
carbapenems
ssx mimic Friedreich ataxia and include ataxia (due to degeneration of spinocerebellar tracts), loss of position and vibration sense (due to degenration of dorsal columns) and loss of DTRs (due to peripheral nerve degeneration)
dx?
vitamin E deficiency
<2yo with low grade fever, cough, tachypnea, and increased work of breathing; exam shows diffuse wheeze and crackles
dx?
etiologic agent?
viral bronchiolitis
RSV
AE of Amphotercin B
renal toxicity causing severe hypoK and hypoMg
blotchy red muscle fibers on Gomori trichrome stain are characteristic of..
mitochondrial myopathies
what is a cofactor used by hydroxylase enzymes in the synthesis of tyrosine, dopamine, and serotonin?
tetrahydrobiopterin (BH4)
what is often first line treatment for essential tremor?
why?
beta blockers
prevent the interaction of epi and NE with receptors at adrenergic synapses; in ET it helps dampen the sensitivity of muscle spindles, which improves tremor symptoms by smoothing out the force of contraction
neurodegenerative diseases like AIDS dementia can be associated with …
hydrocephalus ex vacuo due to significant cortical atrophy, which allows the ventricles to expand while maintaining normal pressure
How does capsaicin work for decreasing chronic pain?
topically, causes defunctionalization of afferent pain fibers and depletion of substance P
What cellular receptor goes with these virions?
CMV
EBV
HIV
Rabies virus
Rhinovirus
- CMV - cellular integrins
- EBV - CR2 (CD21)
- HIV - CD4 and CXCR4/CCR5
- Rabies - nicotinic acetylcholine receptor
- Rhinovirus - ICAM-1 (CD54)
pt was camping, now has progressive agitation, disorientation, and pharyngospasms
infected with what?
rabies - from rhabdoviridae family
What is the outer membrane of gram negative bacteria composed of?
What regions is this molecule arranged into?
What do these regions do?
LPS (lipopolysaccharide)
heat stable molecule arranged into three regions:
- O antigen - cell wall outer membrane polysaccharide antigen used to classify gram negative bacteria
- core polysaccharide - ??
- Lipid A - responsible for the toxic properties of LPS that lead to sepsis and endotoxic septic shock
How does Lipid A from LPS induce shock?
activation of macrophages and granulocytes - activation results in the synthesis of endogenous pyrogens such as IL-1, prostaglandins, and the inflammatory mediators (TNFa and IFN)
these cytokines induce a febrile response by the action of IL-1 on the HT, as well as hypotension, increased vascular permeability with third spacing of fluids, diarrhea, DIC, and death
What is the virulence factor of E. coli strains that cause neonatal meningitis?
synthesize K-1 capsular antigens
What are some organisms that use fimbriae or pili as virulence factors allowing them to adhere to their target tissues?
Neisseria meningitidis, uropathogenic and diarrheogenic E. coli, Bordetella pertussis, and Vibrio cholerae
Describe the forms of giardia lamblia
- 2 forms:
- trophozoite (pathogenic stage)
- bilaterally symetric, pear shaped, multiple flagella and 2 nuclei (owls eye appearance)
- cyst (infective stage)
- oval and contain up to 4 nuclei
- trophozoite (pathogenic stage)
How do you confirm dx of giardia?
What can you do if stool is undiagnostic?
stool microscopy for ova and parasites or fecal immunoassays for giardia ags
small bowel biopsy is sometimes performed when stool studies are nondiagnostic and can show varying degrees of villus atrophy and crypt hyperplasia depending on disease severity
What are some major immune mechanisms against Giardia?
- CD4+ T helper cells
- secretory IgA production
- prevent and clear infection by binding to trophozoites and impairing their adherence to the upper small-bowel mucosa
In pts with sickle cell anemia and other chronic hemolytic disorders, the MC viral cause of aplastic crisis is …
infection of erythroid precursors with Parvovirus B19, a nonenveloped, single stranded DNA virus
major cause of acute renal failure in children; characterized by triad of renal insufficiency, thrombocytopenia, and microangiopathic hemolytic anemia
HUS - hemolytic uremic syndrome
from EHEC with O157:H7 serotype
what is the primary reservoir for EHEC?
how do humans get it?
GI tract of healthy cattle
consuming contaminated or undercooked beef
toxin ingestion that causes cranial nerve deficits and descending symmetric paralysis?
how does the bacteria survive adverse conditions?
botulinum toxin
spore formation which occurs in the subterminal location
What is the tx for gonorrhea and chlamydia?
ceftriaxone is given for N gonorrheae, and doxy or azithro is given for C. trachomatis
What is the major adaptive immune mechanism that prevent reinfection with the influenza virus?
anti-hemagglutinin antibodies
The EHEC strain in particular is unable to…
which is in contrast to most e. coli strains
ferment sorbitol and does not produce glucuronidase
this toxin has both edema factor and lethal factor
what do each of these factors do?
- anthrax exotoxin
- edema factor
- increases CAMP concentration by acting as an adenylate cyclase, causing edema and phagocyte dysfunction
- lethal factor
- Zinc dependent protease that inhibits mitogen-activated protein kinsase signaling, causing apoptosis and multisystem physiologic disruption
disinhibits adenylate cyclase through Gi ADP-ribosylation, increasing cAMP levels; causes edema and phagocyte dysfunction
toxin?
etiologic agent?
pertussis toxin
Bordetella
functions as an adenylate cyclase, increasing cAMP levels; causes edema and phagocyte dysfunction
toxin?
etiologic agent?
adenylate cyclase toxin
Bordetella
recruits and activates neutrophils, leading to release of cytokines that cause mucosal inflammation, fluid loss and diarrhea
toxin?
etiologic agent?
toxin A
clostridium difficile
induces actin depolymerization, leading to mucosal cell death, bowel wall necrosis and pseudomembrane formation
toxin?
etiologic agent?
toxin b
C diff
halts protein synthesis by diabling the 60S ribosomal subunit, leading to intestinal epithelial cell death and diarrhea
toxin?
etiologic agent?
shiga toxin
Shigella dysenteriae
acts as a superantigen, inducing fever and shock, a/w scarlet fever and streptococcal toxic shock syndrome
toxin?
etiologic agent?
pyrogenic exotoxin
streptococcus pyogenes
damages erythrocyte membranes, causing beta hemolysis
toxin?
etiologic agent?
streptolysin O&S
streptococcus pyogenes
What are common agents responsible for septic abortion?
S. aureus and E. coli
test used to evaluate the association between two categorical variables
chi square test
measure of strength and direction of a linear relationship between 2 quantitative variables
correlation coefficient
what is at the apices of glandular cells and consist of two closely adherent cytoplasmic membranes without an intervening space?
tight junctions (zona occludens)
delicate network of cytoplasmic filaments that radiate fromt he cell membrane to hold adjacent cells together
intermediate junctions (zonula adherens)
small, circular, adherent patches circumferentially placed around cells; particularly common in stratified squamous epithleium and contirbute significantly to the structural cohesiveness of tissues subject to mechanical stressors
desmosomes
how do osteocytes remain attached for communication?
gap junctions
what should be monitored after evacuation of hydatiform mole?
b-hCG looking out for malignant transformation - invasive mole or choriocarcinoma
When would I see target cells?
- reduced erythrocyte cell volume from deficient hemoglobin synthesis (thalassemia, iron deficiency) or structural mutations to hemoglobin (sickle cell)
- excessive erythrocyte cellular membrane due to greater cholesterol-to-phospholipid rations (eg obstructive liver disease) or splenectomy
aggregated deposits in erythrocytes that are often seen in patients with sideroblastic anemia, appear as dark blue inclusions
pappenheimer bodies
clusters of DNA remnants in erythrocytes due to hyposplenism or asplenism; appear as peripheral, round, dark purple, blue, or red inclusions
Howell-Jolly bodies
aggregates of denatured hemoglobin that may be present in erythrocytes when patients have glucose-6-phosphate deficiency or thalassemia; not seen on routine staining
Heinz bodies
low surface area-to-volume rations and more susceptible to osmotic stress; seen in hemolytic anemia and hereditary spherocytosis
spherocytes
when would I see basophilic stippling in erythrocytes?
thalassemias, alcohol abuse, and lead/heavy metal poisoning
What are clinical features of DiGeorge Syndrome?
- Conotruncal cardiac defects (tetrology of fallot, truncus arteriosus, interrupted aortic arch)
- Abnormal facies
- Thymic hypoplasia/aplasia (T-cell deficiency)
- Craniofacial deformities (cleft palate)
- Hypocalcemia/Hypoparathyroidism
What is the MOA of organophosphate poisoning?
How would I tx organophosphate poisoning?
- irreversible cholinesterase inhibitors; elicit cholinergic stimulation that lasts until new cholinesterase enzymes are synthesized
- muscarinic antagonists (eg atropine) and pralidoxime (PAM), a drug that reactivates acetylcholinesterase by binding organophosphates and decoupling them from the enzyme
embryologically, what is the fetal GU tract derived from?
What is the last segment of the fetal ureter to canalize?
metanephric blastema and the ureteric bud (dorsal outgrouth from the mesonephric duct)
ureteropelvic junction (UPJ)
Airway resistance is _____ in the trachea and reaches a _____ in the medium sizewd bronchi, where total cross-sectional area is at a _________.
high
peak
minimum
Airway resistance then progressively __________ as total cross-sectional area _________ through the smaller bronchioles, terminal bronchioles, and alveoli.
decreases
increases
hemophilia A is an X linked disorder associated with a deficiency of…..
what Mab mimics the activity of this missing piece and what does it do?
Factor VIII
Emicizumab
binding to both factor IXa and factor X, bringing them into close proximity to allow for factor X activation
What cleaves Ultra-large von Willebrand factor multimers produced by endothelium?
Loss of this thing that cleaves results in what?
ADAMTS13
loss of activity leads to thrombocytopenic purpura
What might be a concern in a pt with chronic corticosteroid dependent asthmatic pts with eosinophilia?
What would I see clinically with this pt?
allergic bronchopulmonary aspergillosis (ABPA)
transient recurrent pulmonary infiltrates and eventual proximal bronchiectasis
cherry red macula + hypotonia, neuro degneration (failure to progress developmentally) + heptosplenomegaly
Niemann-Pick Disease
respiratory failure, hypoxemia, and thickened bronchial walls with inflammatory infiltrates and mucous gland enlargement
dx?
chronic bronchitis
when will I see hemosiderin laden macrophages located in the lungs?
due to chronic passive lung congestion in the setting of heart failure (eg L ventricular systolic dysfunction)
easy bruising, mucosal bleeding, and perifollicular petechial hemorrhages, periodontal disease and poor wound healing, and hyperkeratotic follicles with corkscrew hair
dx?
scurvy from vit C deficiency
Why is vitamin C necessary on a biochem level?
hydroxylation of proline and lysine residues during collagen synthesis
In pts with chronic aortic stenosis and concentric left ventricular hypertrophy what significantly contributes to L ventricle filling?
atrial contraction
loss of atrial contraction due to Afib can reduce left ventricle preload and cardiac output sufficiently to cause systemic hypotension
What would be a diagnostic lab for parotitis?
amylase
what causes calcium to bind to albumin?
elevated pH/alkalosis
In fetal development, what limits the ascent of the horseshoe kidney?
IMA
what happens when the vitelline duct persists?
connection is formed betweent he intestinal lumen and the outside of teh body at the umbilicus;
discharge of meconium from the umbilicus will be seen
direct connection between the bladder lumen and the outside of the body at the umbilicus is called
a persistent urachus or urachal fistula
what hormones contribute to glucose homeostasis in prolonged fasting?
cortisol and growth hormone
what hormone increases the transcription of enzymes involved in gluconeogenesis as well as those involved in lipolysis and proteolysis
cortisol
long standing pattern of eccentric behavior, odd beliefs, perceptual distortions, and social anxiety despite familiarity
schizotypal personality disorder
sarcoidosis is thought to result from a dysregulated cell-mediated immune response to an unidentified antigen, which causes formation of granulomas. What T cells and cytokines drive this process?
Th1 subtype of CD4 helper T cells
activated antigen presenting cells produce IL-2, which stimulates the differentiation of Th1 cells
Th1 cells secrete IL-2 adn IFNy
activated macrophages and T cells also produce TNFa
MOA of mifepristone and misoprostol
progesterone antagonist and PGE1 agonist
What drug will improve survival in pts with CHF and reduced L ventricular EF?
Mineralcorticoid receptor antagonists (eg spironolactone, eplerenone)
List organ susceptibility of infarction from greatest risk to least risk
CNS
myocardium
kidney
spleen
liver
what is a tx that acts like FSH to trigger the formation of a dominant ovarian follicle?
menotropin (human menopausal gonadotropin)
Integral membrane proteins contain _____________ domains composed of ____________ with hydrophobic amino acid residues (eg alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, and glycine).
What is their importance?
transmembrane
alpha helices
anchor the protein to the phospholipid bilayer of the cell membrane
What is the MC CFTR gene mutation?
What does this cause?
3-base pair deletion of phenylalanine at aa position 508
F508
causes impaired post-translational processing (eg improper folding and glycosylation)
unconscious shifting of emotions or desires associated with a person from the past to another person in the present
transference
What cytokine gets to play an important role of anti-inflammatory and immunomodulatory roles, esp. seen with IBD?
how?
IL-10
attenuates the immune response through the inhibiton of Th1 cytokines, reduction of MHC class II expression, and suppression of acitvated macrophages and dendritic cells
Renal disease a/w multiple myeloma is due to…
MCC by light chain cast nephropathy, in which free light chains form obstructive casts in the renal tubules
How can you tx cystic fibrosis pts with rx?
pancreatic enzyme supplementation can tx the malabsorption secondary to pancreatic insufficiency
What keeps mycobacterium tuberculosis from being destroyed by macorphages?
how does this also help drive the formation of caseating granulomas?
cord factor- a hydrophobic surface glycolipid that arranges the cells into long, slender, serpentine cords
forms a highly toxic crystalline monolayer on hydrophobic surfaces
What protein and its ligand will downregulate the immune response by inhibiting cytotoxic T cells?
How might cancers use this binding to its advantage?
What kind of drugs can combat this?
programmed cell death protein 1 (PD-1) and PD-L1
many types of cancers evade immunodetection by increasing expression of PD-L1 on their surface
Mabs v PD-1 upregulate the T-cell response and promote tumor cell apoptosis
Mabs v PD-1
Mabs v PD-L1
- pembrolizumab and nivolumab
- atezolizumab
What kind of murmur might I hear with pulmonary HTN and RV enlargement?
holosystolic tricuspid regurg
What genetic mutation might be a/w PAH from proliferative vasculopathy of the pulmonary arteriolar smooth muscle?
BMPR2 mutation
What is a potent vasoconstrictor that also promotes smooth muscle cell proliferation, found in high concentrations in pts with PAH and it is an important target of therapy?
endothelin
bosentan and ambrisentan are endothelin receptor antagonists that do what?
inhibit pulmonary arteriolar smooth muscle proliferation and alleviate vasoconstriction to lower pulmonary arterial pressure and improve dyspnea in pts with PAH
Pts with CKD often develop symptomatic anemia as GFR declines. Why does this happen?
MC due to inadequate secretion of EPO, a glycoprotein hormone produced by peritubular fibroblasts int he renal cortex in response to tissue hypoxia
infant with intermittent episodes of tonic posturing, poor feeding, vomiting, and irritability; diapers smell like ‘carmelizing sugar’
dx?
mechanism of disease?
Maple syrup urine disease (MSUD)
defective breakdown of branched-chain amino acids (leucine, isoleucine, and valine)
Branched-chain alpha-ketoacid dehydrogenase (in addition to pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase) requires what 5 cofactors?
Thiamine, Lipoate, Coenzyme A, FAD, NAD
mnemonic: tender loving care for nancy
How do you tx Maple syrup urine disease?
What will happen if untreated?
what gives the urine a sweet odor?
high dose thiamine tx, life long dietary restrictions of leucine, isoleucine, and valine
accumulation of branched chain aa in peripheral tissues, resulting in neurotoxicity that includes seizures, irritability, lethargy, and poor feeding
metabolite of isoleucine
What is necessary for the transamination and decarboxylation of amino acids, for gluconeogenesis, and for other essential biochemical processes?
Pyridoxine (vit B6)
What is a cofactor for all 4 carboxylase enzymes?
(pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and 3-methylcrontonyl-CoA-carboxylase)
biotin (vit B7)
What is used in dehydrogenase reactions involving FMN and FAD?
Riboflavin (vit B2)
What serves as a coenzyme for a number of important dehydrogenase enzymes, including transketolase, alpha-ketoglutarate dehydrogenase, and pyruvate dehydrogenase?
thiamine (vit B1)
applying an aniline dye (eg carbolfuchsin) to a smear and then decolorizing with acid alcohol to reveal whether the organisms present are….
this would mean they have what in their cell wall?
acid fast
mycolic acid
surface marker of the monocyte-macrophage cell lineage?
CD14
What is the role of ATP in skeletal and cardiac muscle contraction?
to release the myosin head from its actin binding site and then to energize a conformational change that resets the myosin head to “contract” again the next time it binds to actin
when the effect of an exposure on an outcome is modified by another variable is….
it can be identified using stratified analysis which is….
how is this differentiated from confounding?
effect modification
analyzing the cohort as different subgroups
in confounding, stratification usually reveals no significant difference between the strata
ssx: unilateral facial pain that worsens with jaw movement, HA, and ear discomfort.
dx?
what nerve is most involved and how?
temporomandibular disorder (TMD)
mandibular nerve of trigeminal - sensation to TMJ and mandibular teeth as well as floor of mouth, inside of cheeks, anterior tongue, and much of the skin on lower face; innervates muscles of mastication as well plus mylohyoid, tensor veli palatini, and tensor tympani in middle ear.
what carries mainly sensory fibers from the cheek, nares, upper lip and teeth, the pharyngeal palate and the maxillary sinuses?
maxillary division of trigeminal
In aplastic anemia, what would the reticulocyte count be?
low, due to few progenitor cells
low hemoglobin, thrombocytopenia, and absent hematopoietic cells in the bone marrow is consistent with…
what hormone will be elevated?
aplastic anemia
EPO
What are the rubber like properties of elastin due to?
high content of nonpolar/hydrophobic amino acids and extensive cross-linking between elastin monomers facilitated by lysyl oxidase
tx for acute angle-closure glaucoma?
MOA?
Where is this enzyme found and what does it do?
This drug results in…
acetazolamide
inhibiting the enzyme carbonic anhydrase
PCT - responsible for catalyzing reactions necessary for NaHCO3 reabsorption
enhanced HCO3 and water excretion as well as increased urinary pH and potential metabolic acidosis
bioavailability equation?
F= (AUC oral x IV dose)/(AUC IV x oral dose)
What are three variables that affect the total oxygen content of blood?
What is a common cause of anemia in premenopausal women?
hemoglobin concentration, SaO2, and PaO2
chronic blood loss secondary to menstruation - will have decreased hemoglobin, while SaO2 and PaO2 are staying the same
How will obesity change lung function?
will cause alveolar hypoventilation due to reduced chest wall compliance
V/Q mismatch
Cyanide inhibits cellular oxidative phosphorylation by …
this will cause…
What will may SaO2, PaO2 and CaO2 be?
What value will change?
inhibiting Fe3+ in cytochrome c oxidase
lower peripheral tissue O2 consumption
all these values will remain the same
venous oxygen content rises and the a-v oxygen gradient falls
in eukaryotic gene transcription, what enzyme uses a DNA template to generate complementary mRNA, which is then processed and translated into protein?
nuclear RNA polymerase II
What directly bind general transcription factors and RNA polymerase II upstream from the gene locus, which is necessary for the initiation of transcription?
Promoter sequences
What are the two types of eukaryotic promoter regions?
- TATA/Hogness box - 25 bases upstream from the gene being transcribed
- CAAT box - 70-80 bases upstream from the gene
What do enhancer sequences do?
- bind activator proteins that facilitate bending of DNA
- allows activator to interact with general transcription factors and RNA polymerase II at the promoter
- increases rate of transcription
- allows activator to interact with general transcription factors and RNA polymerase II at the promoter
What decreases transcription rates by binding repressor proteins?
silencers
immunoglobulin M antibodies against self IgG is called
rheumatoid factor
What are the seronegative spondyloarthropathies?
- psoriatic arthritis
- ankylosing spondylosis
- IBD
- reactive arthritis
What are class I HLA proteins v class II HLA proteins?
Class I HLA includes HLA B27 (PAIR acronym of seronegative)
Class II HLA includes DR, DP, DQ (rheumatoid arthritis, DMTI, celiac disease)
What directs pyruvate toward becoming glucose or going to Kreb cycle? What enzymes does this work on?
Acetyl-CoA will activate pyruvate carboxylase to go to send to oxaloacetate and into gluconeogenesis
Acetyl-CoA will inhibit pyruvate dehydrogenase to down regulate Acetyl-CoA production and continuation into the Krebs cycle
What are the autoantibodies associated with SLE?
- antinuclear abs - found in virtually all SLE pts but also in many other disorders
- anti-dsDNA abs - highly specific for SLE, but only about 60% of SLE pts have high titers
- anti-Smith abs - abs against small nuclear ribonucleoproteins) are present in 20-30% of pts but are also highly specific
What controls cell cycle progression from G1 to S?
what are they activated by?
what do they do?
how does cancer exploit this?
cyclin dependent kinases (CDKs) 4 and 6
cyclin D
inhibit the retinoblastoma tumor suppressor protein, leading to the upregulation of transcriptional factors that progress the cell cycle to S phase
achieve unregulated cell growth via cyclin D amplification (or inactivating mutations to retinoblastoma gene)
What drugs are CDK 4/6 inhibitors?
MOA?
palbociclib
block the cyclin D binding site on CDK, reducing activation, increase retinoblastoma tumor suppressor protein, and cell cycle arrest
MOA of diphenoxylate?
how do you discourage abuse of this drug?
- opioid anti-diarrheal, structurally related to meperidine
- binds mu opioid receptors in GI tract to slow motility
- combine with atropine, produces adverse ssx (dry mouth, blurry vision, nausea)
How are erythrocyts broken down (esp like in a bruise)?
- erythrocyte destruction causes the release of iron-containing heme molecules
- heme oxygenase (contained in macrophages) degrades heme into biliverdin, carbon monoxide, and ferrous iron while consuming oxygen adn electrons provided by NADH and NADPH-cytochrome P450 reductase
- biliverdin is green in color and is further reduced (by biliverdin reductase) to the yellow pigment bilirubin
- bilirubin is then transported to the liver bound to albumin
What is the final enzyme in the heme synthetic pathway?
what is it inhibited by?
ferrochelatase
inhibited by lead
autosomal dominant disorder of the heme synthesis pathway caused by porphobilinogen (PGB) deaminase deficiency?
What does this cause?
what is a key features of acute porphyrias?
acute intermittent porphyria (AIP)
nervous system dysfunction due to the accumulation of early heme pathway intermediates (PBG and delat-aminolevulinic acid [ALA])
presents acutely with varibale GI and neuro ssx, MC abdominal pain, vomiting, peripheral neuropathy, and neuropsychiatric derangements
reddish urine that darkens on exposure to light and air due to the oxidation of excess PBG
How would you treat or prevent acute porphyria attacks?
inhibit ALA synthase (the rate limiting enzyme of heme synthesis) to reduce formation of teh toxic intermediate metabolites
ALA synthase is upregulated by…
and downregulated by…
CYP450 inducers (most anti-epileptics, griseofulvin, rifampin)
heme and glucose
pulmonary edema in the alveoli impairs ventilation and causes intrapulmonary shunting by
decreasing lung compliance
How should phosphatidylcholine, phosphatidylglycerol, and sphingomyelin concentration in amniotic fluid change during pregnancy?
What ratio do we look at concerning these?
- fetal lung phosphatidylcholine (lecithin) production increases sharply after 30 weeks gestation
- fetal lung phosphatidylglycerol prodyction increases at 36 weeks gestation
- amniotic fluid sphingomyelin level should remain approximately constant during 3rd tri
- L/S ration > 2 indcates adequate surfactant production to avoid neonatal hyaline membrane disease
What is used during anesthesia to assess the degree of paralysis induced by NMJ blocking agents?
train-of-four (TOF) stimualtion
What is the difference in train of four stimualtion when looking at a non-depolarizing NMJ blocker and a depolarizing blocker?
What is an example of each drug?
- nondepolarizing (vecuronium, pancuronium, and tubocurarine)
- shows a progressive reduction in each of the four responses
- depolarizing (succinylcholine)
- phase I -equal reduction of all four twitches
- phase II - progressive reduction in the four responses
What drug will reverse nondepolarizing NMJ blockade?
neostigmine
Klinefelter syndrome is MCC by …. during parental gametogenesis that results in what karyotype?
meiotic nondisjunction
47, XXY (variants 46, XY/47,XXY mosaicism and 48, XXXY)
Klinefelter syndrome is usually not diagnosed until puberty, when what characteristic physical findings begin to develop?
- primary testicular failure due to hyalinization and fibrosis of seminiferous tubules
- small firm testes and azoospermia
- leydig cell dysfunction, testosterone deficiency
- FSH and LH increased secondary to gonadal failure
- eunuchoid body habitus (due to testosterone failure)
- tall stature and gynecomastia
- facial and body hair is sparse or absent
- decreased muscle mass
- mild intellectual disability is seen in some pts
- majority with normal intelligence
- psychosocial abnls common
Each MHC class I molecule consists of…
a single heavy chain and associated beta-2 microglobulin
MHC class II molecules consist of…
alpha and beta polypeptide chains
What types of antigens go to MHC I v MHC II?
How are they processed?
- MHC class I
- viruses, tumor proteins
- antigens are processed in cytoplasm
- MHC class II
- bacterial
- antigens are phagocytosed and digested by lysosomes within which antigen binds to MHC II
MHC I v MHC II angiten presentation end results?
- MHC I
- apoptosis of the presenting cell
- MHC II
- activation of TH cells, which stimulate the humoral and CM immune responses
gonorrhea first line tx?
ceftriaxone and azithromycin
(3rd gen ceph + macrolide)
In the lungs, the binding of O2 to hemoglobin drives the release of H+ and CO2 from hemoglobin. This is called…
in contrast, in the peripheral tissues, high concentrations of CO2 and H+ facilitate O2 unloading from hemoglobin. This is called…
the Haldane effect
the Bohr effect
Pts with primary adrenal insufficiency present with what kind of labs?
hypoNa, hyperK, hyperCl, and non-anion gap metabolic acidosis
What is the down stream effect of NE?
increases cAMP within cardiac myocytes and leads to increased contractility, conduction, and heart rate
peripheral vasoconstriction occurs via stimulation of alpha1 adrenoreceptors in vascular smooth muscle cells and activation of an IP3 signaling pathway
What is the primary effect of alpha2 receptor stimulation?
decreased cAMP
- CNS sympatholytic
- decrease insluin release by pancreatic beta cells
- decrease intestinal motility
Stimulation of beta-1 receptors causes
increase cAMP
- increase cardiac contractility and HR
- increase renin release by JG cells
activation of Beta 2 receptors causes
increase cAMP
- peripheral vasodilation
- bronchodilation
- increase glucagon release by pancreatic alpha cells
alpha 1 receptor activation results in
increase IP3
- peripheral vasoconstriction
- urethral constriction
- pupillary dilation (via radial muscle contraction)
EPO signal transduction is primarily mediate by..
janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) pathway, which promotes erythrocyte precursor survival
What happens to the spleen in sickle cell anemia?
functional asplenia within the first 18-36 months of life due to repeated microinfarction of splenic vascular beds
What blocks the binding of RANK to RANKL? What does this cause?
Osteoprotegerin (OPG)
reduces formation of mature osteoclasts
How do low estrogen states cause osteoporosis?
decrease osteoprotegerin production, increasing RANK-L production, and increasing RANK expression in osteoclast precursors
What would a low OPG:RANK-L ratio cause?
an increased ratio?
increased osteoclast formation and activity
decreased osteoclast formation and survival
After Ras is GTP bound, it begins a phosphorylation cascade that results in the activation of…
mitogen-activated protein kinase (MAPK), which enters the nucleaus to influence gene transcription
When mRNA is first transcribed from DNA, it is in an unprocessed form called…
pre-mRNA or heterogeneous nuclear mRNA (hnRNA)
What must happen to pre-mRNA/hnRNA before it can leave the nucleus as mRNA?
- 5’ capping
- poly A tail addition
- intron splicing
Once mRNA is finalized, it leaves the nucleaus bound to specific packaging proteins. It enters the cytoplasm and can associate with ribosomes to undergo translation. Certain mRNA sequences instead associate with…
what does this do?
proteins that are found in P bodies
distinct foci found in eukaryotic cells that are involved in mRNA regulation and turnover
fundamental role in translation repression and mRNA decay
What do P bodies contain?
What do they function as?
numerous proteins including RNA exonucleases, mRNA decapping enzymes, and constituents involved in mRNA quality control and microRNA-induced mRNA splicing
function as a form of mRNA storage, as certain mRNAs are incorporated into P bodies only to be later released and utilized for protein translation
If a Meckel diverticulum pt actually is symptomatic, how will they present?
spontaneous but painless lower GI bleeding
also possible lead point for intussusception which can present with colicky abdominal pain and ‘currant jelly’ stools
increased uptake of 99mTc-pertechnetate in the periumbilical/RLQ is characteristic of…
meckel diverticulum
What kind of receptors are calcium sensing receptors?
What do they do?
transmembrane Gq-protein coupled (metabotropic) receptors that regulate the secretion of PTH in response to changes in circulating calcium
familial hypocalciuric hypercalcemia is a disorder of what?
benign autosomal dominant disorder caused by defective calcium sensing receptors in the parathyroid galnd and kidneys
What are the pressure changes in aortic regurgitation?
- reduced aortic diastolic pressure
- increased aortic systolic pressure
- increased LV diastolic and systolic pressures
What are the hemodynamic changes associated with aortic regurg?
- rapid fall in aortic pressure during diastole
- increase in LVEDV
- compensatory increase in stroke volume
In spherocytosis, what is increased due to mild dehydration of the RBC?
MCHC - mean corpuscular hemoglobin concentration
What are some markers of hemolysis?
elevated LDH
reticulocytosis
decreased haptoglobin
What is the MOA of fenoldopam and what is an indication?
- selective peripheral dopamine-1 receptor agonist
- arteriolar dilation
- increases renal perfusion
- promotes diuresis and natriuresis
- given IV to lower BP in hypertensive emergency
- esp in pt with AKI
What type of drug is phenelzine?
MAO-I (non-selective)
What is Sydenham chorea and what is it associated with?
non-rhythmic movements of the hands, feet, and face; sudden changes in voice pitch and volume
a/w acute rheumatic fever
lens shaped structure located ventral to the thalamus, dorsal to the substantia nigra, and medial to the internal capsule;
a component of the basal ganglia and plays an important role in the modulation of basal ganglia output
subthalamic nucleus
What will damage to the subthalamic nucleus cause?
When would injury to this area occur?
decrease excitation of the globus pallidus internus, reducing inhibition of the thalamus
results in CL hemiballism
MC occurs in the setting of lacunar stroke; often a consequence of long-standing HTN and DM
atrophy of the caudate nucleus occurs in…
Huntington disease
atrophy of the lentiform nucleus (eg globus pallidus and putamen) occurs in
Wilson disease
What do abnormal aPTT and PT suggest, respectively?
- abnormal aPTT - problem with intrinsic pathway
- VIII, IX, XI, XII
- abnormal PT - problem in extrinisc pathway
- VII
How do platelet defects present differently than coagulopathies?
- coagulopathies generally present deep-tissue bleeding into joints, muscles, and subcutaneous tissue
- platelet defects typically manifest with mucocutaneous bleeding
hereditary breast cancer is most commonly associated with mutations in what genes?
these tumor suppressor genes are involved with what?
BRCA1 and BRCA2
involved in DNA repair and their mutation increases the risk of developing breast and ovarian cancer
A live attenuated oral vaccine will have an increased response in what, compared to an inactivated IM vaccine?
LA oral vaccin produces a stronger mucosal secretory IgA immune response
this increase in mucosal IgA offers immune protection at the site of viral entry by inhibiting attachment to intestinal epithelial cells
disease with defective peroxisomal biogenesis; presents in early infancy with craniofacial abnormalities (widened sutures, large anterior fontanelle), hepatomegaly, and profound neuro deficits
Zellweger syndrome
the buildup of very long chain and branched-chain fatty acids due to impaired oxidation is the hallmark of ….
accumulation of these fatty acids results in…
peroxisomal disorders (eg Zellweger syndrome, adrenoleukodystrophy)
in the brain, results in permanent neuro dysfunction
After endothelial damage, vWF binds…. on the platelet membrane and mediates…. to subendothelial collagen.
binds GP Ib receptors
platelet adhesion
deficiency of vWF impairs platelet adhesion and can lead to easy bruising and …
prolonged mucocutaneous bleeding (gingival bleeding, heavy menses)
Lab work up in vWF deficiency reveals what?
normal platelet count and an abnormal ristocetin cofactor assay
measures in-vitro, vWF-dependent platelet agglutination (indicative of impaired platelet adhesion in-vivo)
What does ristocetin do?
activates GP Ib receptors on platelets and makes them available for vWF binding; when vWF level is decreased there is poor platelet agglutination in the presence of ristocetin
