Uworld 5 Flashcards
infertility in men due to absent vas deferens - dx?
CF
Structures derived from neural crest cells
- Schwann cells
- odontoblasts
- melanocytes
- enterochromaffin cells
- spinal membranes
- adrenal medulla/ganglia
- laryngeal cartilage
- tracheal cartilage
What will you see in the lung shortly after an MI?
acute pulmonary edema - transudate from elevated hydrostatic pressure in the pulmonary venous system leads to engorged alveolar capillaries with transudation of fluid into the alveoli
appearing as acellular pink material on histology
What is similar to G6PD deficiency and how do they fit together?
Glutathione reductase deficiency has a similar clinical consequence as its absence results in an inability to utilize NADPH to reduce glutathione
both result in bite cells
fever, delirium, mucosal and axillary dryness, cutaneous flushing, nonreactive mydriasis, and urinary retention, tachycardia and decreased bowel sounds
OD??
anticholinergic toxicity (TCAs like amyltriptyline)
Why would women present later than men with hemochromatosis?
physiologic iron loss through menstruation and pregnancy slows the progression of hemochromatosis in women
What is the major amino acid responsible for transferring nitrogen to the liver for disposal?
alanine
what kind of study begins with selecting individuals who have the outcome (‘cases’) and individuals who do not have the outcome (‘controls’) and then retrospectively comparing their history of exposure to risk factors
case-control study
heavy smoker, high fever, diarrhea, headache and confusion;
lab shows hyponatremia
productive cough
etiology?
legionella pneumophila
what produces beta-hCG? When is it detectable in serum and urine?
synctiotrophoblast after implantation
serum - 8 days s/p fertilization
urine -14 days
lipoprotein lipase deficiency causes what syndrome?
How do these patients present?
Familial chylomicronemia syndrome
presents in childhood with marked hypertriglyceridemia, recurrent acute pancreatitis, lipemia retinalis (milk-appearing retinal vasculature), and eruptive xanthomas (small yellowish papules surrounded by erythema found mainly on extensor surfaces
Most often, Down syndrome cases arises due to nondisjunction during…
How can I tell this on and RFLP?
maternal meiosis I
The child has 2 bands from mom and 1 band from dad (inheriting both homologous chromosomes)
if it was during meiosis 2, it would be one band from each parent, with one of the bands being thicker (inheriting sister chromatids)
What creates defense from Candida locally and systemically?
Local defense is performed by T cells while systemic infection defense is performed by neutrophils
Penicillins and cephalosporins function by…
irreversibly binding to penicillin-binding proteins such as transpeptidases
Where is elastase found?
neutral protease contained in macrophage lysosomes and in azurophilic (primary) granules of neutrophils
What are my proteases and anti-proteases that balance them?
- Proteases
- elastase
- Cathepsin G
- Matrix Metallo-proteinases
- Antiproteinases
- Alpha-1 antitrypsin
- alpha-2 macroglobulin
- TIMPs
impaired beta-oxidation is most often caused a deficiency in…
medium chain acyl-CoA dehydrogenase deficiency
On release from the SR, calcium binds to… on the thin filaments. This induces a conformation change in the … causing it to displace… and expose the myosin binding sites on the actin filaments
troponin C
troponin complex
tropomyosin
What does PAS stain end up highlighting?
polysaccharides of fungal cell wall, mucosubstances secreted by epithelia, and basement membrane
evaluating tissue for Whipple disease
Peroxidase staining can be used to differentiate subtypes of…
while horseradish peroxidase is useful in…
acute leukemia
immunoblotting (eg, Western blot)
calcium appears as a dark purple deposit on…
H&E stain
What stains can be used to identify neutral lipids?
Nile red or Sudan black (with the latter being useful for frozen sections)
Staining with alkaline phosphatase is an enzyme marker of osteoblasts and can be useful in identifying…
bone tumors
persistent pattern of social detachment, preference for solitary activities and limited emotional expressivity when interacting with others
schizoid personality disorder
protein kinase involved in activation of signaling pathways for melanocyte proliferation?
what mutation of this is seen in melanoma?
BRAF
BRAF V600E in 40-60% of pts
MOA of sulfonylureas
inhibit the ATP-sensitive K+ channel on beta cell membrane, inducing depolarization and L type calcium channel opening
the increased Ca2+ influx stimulates beta cell insulin release independent of blood glucose concentrations
Hallmarks of this diagnosis are microangiopathic hemolytic anemia (MAHA) (nonimmune hemolytic anemia with schistocytes) and thrombocytopenia without any other obvious cause
thrombotic thrombocytopenic purpura
What is tx for TTP?
plasma exchange
What should be checked before rx’ing someone dapsone?
G6PD levels because this drug causes oxidative stress
observational study analyzing population-level data to evaluate the association between a potential exposure and a given outcome
ecological study
What is the MC and most severe of the galactosemic disorders?
classic galactosemia
AR, leading to complete enzymatic absence of galactose-1-phosphate uridyl transferase
newborns present within days of birth with jaundice, vomiting, and hepatomegaly
What is Rett syndrome?
X linked dominant, affecting females (affected males die in utero) that presents in early childhood with progressive neurodegeneration and stereotypical hand movements
What is Leber hereditary optic neuropathy inheritance pattern?
mitochondrial inheritance
progressive bilateral optic neuropathy leading to blindness
What do lab studies show in an infant with SCID?
low or absent CD3+ T cells and hypogammaglobulinemia
thymic hypoplasia or aplasia often common
severe bacterial and viral infections in infancy, chronic diarrhea, mucocutaneous candidiasis
SCID
complete or partial deficiency of the enzyme methylmalonyl-CoA mutase
autosomal recessive orgnaic acidemia
methylmalonic acidemia presentation and labs?
dx confirmed with…
complete deficiency of methylmalonyl-CoA mutase classically presents with lethargy, vomiting, and tachypnea in a newborn
labs show hyperammonemia, ketotic hypoglycemia, and metabolic acidosis
confirm with elevated urine methylmalonic acid and propionic acid
How does SCD present in kids?
what does the sickling cause?
dactylitis (painful swelling of hands and feet)
sickling episodes result in hemolysis, which leads to increased indirect bilirubin and lactate dehydrogenase and decreased levels of haptoglobin
calcium efflux from cardiac cells prior to relaxation is primarily mediated by…
Na/Ca exchange pump and SR Ca-ATPase pump
Dermatomyositis may occur alone or as a pareneoplastic syndrome of underlying malignancy, MC due to
adenocarcinom (eg ovary, lung, pancreas)
hereditary PAH is most often due to an inactivating mutation in….
Pts with this mutation have a predisposition for…
BMPR2, transmitted in an autosomal dominant manner with variable penetrance
dysfunctional endothelial and smooth muscle cell proliferation
After IV lorazepam is given for status epilepticus, what is the next drug given and MOA?
phenytoin IV
long acting anticonvulsant that is administered concurrently to prevent the recurrence of seizure activity, regardless of pt response to lorazepam
inhibit neuronal high-frequency firing in the cortex by reducing the ability of sodium channels to recover from inactivation
In CKD, what part of vit D synthesis is impaired?
what else is failing and what does this cause?
25-hydroxyvitamin D to 1,25-hydroxyvitamin D
also have failure of glomerular and tubular function, resulting in phosphate retention and hypocalcemia
compensatory rise in PTH, presenting with weakness, muscle and joint pain, and defective bone mineralization, and increased fx risk
what do you use in tx resistent schizophrenia?
clozapine
affinity for multiple dopamine and serotonin receptors
Children with watery diarrhea should be rehydrated with what?
hypotonic, equimolar concentrations of sodium and glucose to help prevent dehydration and electrolyte abnormalities
sirolimus MOA
binds to immunophilin FK-506 binding protein (FKBP) in the cytoplasm, forming a complex that binds and inhibits mTOR
inhibition of mTOR signaling blocks IL-2 signal transduction and prevents cell cycle progression and lymphocyte proliferation
Bortezomib MOA
binds and inhibits 26S proteasome
in multiple myeloma, it can facilitate apoptosis of neoplastic cells by preventing degradation of pro-apoptotic factors
arrangement in which a payor pays a fixed, predetermined fee to cover all the medical services required by a patient is termed
capitation
what type of plans require patients to have a PCP and obtain referrals for specialty consultations?
point-of-service
Prolactin is manufactured due to stimulation by… while it is inhibited by…
thyrotropin-releasing hormone
inhibited by progesterone
The conjoint tendon is made of what muscles?
common tendon of transversus abdominis and internal oblique muscles; forms part of posterior wall of inguinal canal
superficial and deep inguinal rings are physiologic openings in the
external abdominal oblique aponeurosis and the transversalis fascia respectively
tx and MOA for Hep C
direct acting antivirals - ledipasvir and sofosbuvir
target specific HCV enzymes (eg, protease, NS5A, RNA polymerase), which inhibits viral replication and assembly
What oncogenic mutation is MC a/w glioblastoma?
overexpression of epidermal growth factor receptor (EGFR) on the surface of neoplastic cells
What do interferons do?
suppress viral replication by halting protein synthesis and promoting apoptosis of infected cells, limiting the ability of viruses to spread through the tissues
works only in presence of double stranded RNA, which forms in infected cells as a result of viral replication
Most pts with polycythemia vera have what mutation?
V617F mutation involving JAK2 gene
renders hematopoietic cells more sensitive to growth factors like EPO and TPO
schistocytes on peripheral blood smear indicate what?
How would this affect coagulation studies?
microangiopathic hemolytic anemia (eg, HUS, TTP, DIC, or mechanical damage)
coagulation studies are normal in HUS, TTP but abnormal in DIC
The posteromedial papillary muscle is supplied soley by what artery?
posterior descending artery
What is the primary virulence factor of S. pneumoniae?
polysaccharide capsule that inhibits opsonization and phagocytosis; the polysaccharide capsule of the most virulent strains is targeted by the pneumococcal vaccine, which confers immunity against those subtypes
What are the most coming findings from compression due to transtentorial/uncal herniation?
- ipsilateral oculomotor nerve
- fixed and dilated pupil on side of compression, then ptosis and down and out eye
- ipsilateral posterior cerebral artery
- CL homonymous hemianopsia with macular sparing
- CL cerebral peduncle against tentorium
- damage to CL corticospinal tract - ipsilateral hemiparesis
- brainstem hemorrhage (ie Duret hemorrhages)
- in pons and midbrain d/t rupture of basilar artery
significant panlobular lymphocytic inflammation, which may ‘bridge’ into adjacent hepatic lobules due to collapse of the reticulin framework; spotty areas of hepatocyte injury and ballooning degeneration are also seen in this disease
acute viral hepatitis
damaged cytokeratin filaments within hepatocytes; appear as highly eosinophilic inclusions on microscopy
mallory bodies a/w alcoholism
Ageusia often occurs with what as a common complication of TBIs
how does this happen?
anosmia
acceleration-deceleration forces during head trauma can lead to avulsion of the olfactory nerve rootlets as they traverse the cribiform plate
What kind of immune cascade is responsible for manifestations of toxic shock syndrome?
- superantigens interact with MHC on antigen presenting cells and the variable region of the T lymphocyte receptor
- cause nonspecific, widespread activation of T cells
- release of IL-2 from T cells and IL-1 and TNF from macrophages
What part of the duodenum courses horizontally across the abdominal aorta and IVC at the level of the third lumbar vertebra?
what lies anterior?
third part of duodenum
superior mesenteric vessels lie anterior
What is the only part of the duodenum that is not retroperiotneal?
first part of the duodenum
Where does the fourth part of the duodenum course?
superiorly and to the left of L2 and L3 vertebrae and becomes the jejunum past the ligament of Treitz
physicians or therapist’s conscious or unconscious reaction toward a pt that is based on past personal relationships; provider towards pt
countertransference
redirection of a pt’s emotions from a signifivant person in the past to that pt’s current physician or therapits; pt’s reaction to provider
transference
how can you distinguish secretory diarrhea from inflammatory diarrhea and osmotic diarrhea?
- inflammatory will have blood or pus
- osmotic diarrhea will improve with diet modification
watery diarrhea, hypokalemia, and achlorydria (WDHA) syndrome (pancreatic cholera) is due to…
excessive secretion of VIP
What drugs will increase the prothrombin and activated partial thromboplastin times but do not affect the thrombin time?
Direct Factor Xa inhibitors (apixaban, rivaroxaban)
What drugs are considered direct thrombin inhibitors?
argatroban
bivalirudin
dabigatran
MOA of tamoxifen and raloxifene
SERMs - interact with the estrogen receptor and have either agonists or antagonist activity depending on the tissue;
in breast tissue, tamoxifen has an anti-estrogenic effect (tx ER+ BRCA)
in endometrial tissue, tamoxifen has a stimulatory effect and can lead to development of endometrial hyperplasia and endometrial cancer
rows of RBCs stacked on each other like coins is called what?
why does this happen?
rouleaux formation
due to elevated levels of circulating proteins which disrupts the repulsive electrostatic charge on the RBC surface and causes stacked aggregation
In what disease states might you see rouleaux formation?
can be in inflammatory conditions that increase acute phase reactants (fibrinogen), but classically linked to lymphoproliferative/plasma cell disorders like multiple myeloma and Waldenstrom macroglobulinemia which generate high levels of monoclonal paraprotein (immunoglobulins)
Polyarteritis nodosa commonly affects what organs while it avoids this…
commonly affects kidneys, heart, liver, and GI
avoids lungs/pulmonary arteries and rarely involves bronchial arteries
What will you see on biopsy of Giant Cell Arteritis/Temporal Arteritis?
scattered, focal granulomatous inflammation centered on the media with intimal thickening, elastic lamina fragmentation, and giant cell formation
medial band-like calcifications are characteristic of what disease?
How does this present on XR?
How does it present clinically?
Monckeberg’s medial calcific sclerosis
pipestem calcifications on XR
usually not clinically significant
shrunken and basophilic with loss of the nucleolus describes
pyknotic nucleus
what are red neurons?
basophilic Nissl bodies disappear of the pyknotic nucleus, resulting in cytoplasm that stains deeply eosinophilic
When is bleeding time prolonged?
is a test of platelet function and is prolonged by qualitative and quantitative platelet defects
What is the MC heritable bleeding disorder?
What tests will be abnormal?
von Willebrand Disease (vWD)
prolonged PTT and bleeding time - produced by both endothelial cells and megakaryocytes and functions as a carrier protein for Factor VIII and as a mediator of platelet adhesion to endothelium
What is a transglutaminase that cross-links fibrin polymers, thereby stabilizing clots?
What happens if there is a deficiency in this?
Factor XIII
spontaneous or excessive bleeding, but would not cause prolonged bleeding time, PT or PTT
How does mesothelia appear histologically?
cuboidal or flattened cells (epithelium-like) or spindle cells (stromal like);
immunohistochemistry- nearly all cases stain positive for cytokeratins and many will also stain for calretinin
EM shows polygonal tumor cells with numerous long, slender microvilli and abundant tonofilaments
What arteries lead to the retinal artery?
ICA to ophthalmic artery to retinal artery
What are niacin dependent enzymes in the TCA cycle?
- Pyruvate dehydrogenase
- isocitrate dehydrogenase
- alpha-ketoglutarate dehydrogenase complex
- malate dehydrogenase
Process of base excision repair
- glycosylase
- recognize abnl base then cleave altered DNA base leaving AP site
- endonuclease
- cleaves 5’ end of AP site
- lyase (or phosphodiesterase)
- completes extraction of AP site from DNA molecule by removing rest of sugar-phosphate group
- DNA polymerase
- fills gap with correct sugar-phosphate base
- ligase
- seals the nick
What is Reverse T3?
inactive form of thyroid hormone generated almost entirely from the peripheral conversion of T4
What would giving exogenous T3 do to someone that is already hypothyroid?
rapidly suppress TSH
decrease T4 secretion from thyroid
rT3 decreases bc of less T4
LAD type 1 results from the absence of …
this leads to…
CD18
leads to the inability to synthesize the beta-2 integrins Mac-1 and LFA-1, affecting tight adhesion, crawling, and transmigration
clinical manifestations of this disease include recurrent skin infections without pus formation, delayed detachment of the umbilical cord, and poor wound healing
LAD type 1
PECAM-1 is a/w what process?
transmigration - neutrophils migrate out of vasculature by squeezing in between the cells via integrin attachments and adherence to PECAM-1
What is the main cell in the creation of lung abscesses?
These cells, once activated, secrete what to create this?
neutrophils
release cytotoxic granules (lysosomes) containing myeloperoxidase and other digestive enzymes that destroy extracellular bacteria and recruit additional immune components to the area
can result in liquefying necrosis of lung tissue and (portentially) lung abscess
What is the predominant component of eosinophilic granules and plays a crucial role in the elimination of parasites?
major basic protein
whorled pattern of cellular growth that froms synctial nests, which may calcify and appear as round, eosinophilic laminar structures called psammoma bodies
meningioma
also papillary thyroid carcinoma, mesothelioma, papillary serous carcinoma of the ovary and endometrium
benign tumors that involve the cerebellum in children and young adults; tumor cells typically have eosinophilic granular bodies and elongated hairlike processes (Rosenthal fibers) under light microscopy
pilocytic astrocytomas
most often present as benign suprasellar tumors in children and appear as cords/nests of palisading squamous epithelium with internal areas of lamellar “wet” keratin under light microscopy
adamantinomatous craniopharyngiomas
usually present as paraventricular tumors (eg floor of fourth ventricle) and have characteristic perivascular rosettes under light microscopy
ependymomas
often located in the cerebral hemispheres and may cross the corpus callosum (butterfly glioma);
dx?
what is seen on light microscopy?
Glioblastoma
hypercellular areas of atypical astrocytes bordering regions of necrosis (pseudo-palisading)
malignant cerebellar tumors that typically are in children and are characterized by small blue cells that may surround neuropil, forming Homer-Wright rosettes under microscopy
medulloblastomas
typically involve white matter of cerebral hemispheres and tumor cells have a “fried egg” appearance (round nuclei surrounded by a halo of clear cytoplasm) under light microscopy
oligodendrogliomas
on light microscopy, spindle cells with palisading nuclei arranged around Verocay bodies composed of eosinophilic cores (Antoni A pattern)
Schwannomas
Most cases of Ewing Sarcoma involve translocations of
EWSR1 and FLI1
How are excess vitamin D intake and sarcoidosis similar?
- excess vit D intake
- hypercalcemia causing mental status changes, muscle weakness, constipation, and polyuria/polydipsia
- sarcoidosis
- activated macrophages express 1-alpha-hydroxylase, leading to excess production of 1,25-dihydroxyvitamin D and hypercalcemia
What are the markers seen on lymphoblasts in precursor B-ALL v T-ALL?
TdT+, CD10, CD19 => BALL
CD2, CD3, CD4, CD5, CD7, CD8, TdT, and CD1a
meningococcal septicemia can cause bilateral hemorrhagic infarction of the adrenal glands leading to
Waterhouse-Friderichsen syndrome
placenta that is morbidly adherent to myometrium; scar tissue from prior surgery can results in malformed or absent decidual layer between the placenta and myometrium allowing for direct myometrial attachment by the villous tissue and preventing normal placental separation after delivery
placenta accreta
MCC of postpartum hemorrhage?
uterine atony
failure of uterus to contract adequately s/p delivery
responds to uterotonic agents
in a suprapubic cystostomy, what fascia gets pierced?
- aponeurosis of abdominal wall muscles
- superficial fascia
- transversalis fascia
- extraperitoneal fat
Pts with Sjogren syndrome have a higher rate of what?
thrush, dental caries, and other complications of odontogenic infections (eg osteomyelitis of the mandible) because of loss of protective factors in saliva
positive glycerol lysis test: RBCs are lysed when incubated in hypotonic saline with glycerol
dx test for hereditary spherocytosis
demonstrate increased osmotic fragility due to decreased SA:V
anemia, elevated lactate dehydrogenase, and indirect hyperbilirubinemia suggest…
hemolytic anemia
What are complications of Hereditary spherocytosis?
pigmented gallstones and aplastic crises from parvovirus B19 infection
Pts with Down Syndrome are at increased risk of developing what leukemias or lymphomas?
ALL and AML
Pt gets stabbed above the clavicle and near the manubrium. What are you concerned for?
pneumothorax, tension pneumothorax, or hemothorax
lung apices and cervical pleura extend above the clavicle and first rib through the superior thoracic aperature and into the neck
The ansa cervicalis arises from what nerve roots to innervate what muscles?
from C1, C2, and C3 to innervate the sternohyoid, sternothyroid, and omohyoid
hematogenous osteomyelitis usually affects….
boys, developing on the metaphysis of long bones, as this region contains slow-flowing, sinusoidal vasculature that is conducive to microbial passage
Where does Ewing Sarcoma usually arise?
diaphysis of long bones, esp the femur
Where is the MC location for hematogenous osteomyelitis in adults?
vertebral body, also the location of Pott disease -TB
What is special about the dual circulation of the lungs?
collateral circulation helps protect against lung infarction;
pulmonary arteries supply mostly deoxygenated blood to lungs for gas exchange while bronchial arteries supply nutrients, remove waste, and provide collateral blood flow
histologic findings of patchy lymphoplasmacytic infiltrates, focal fibroblastic proliferation, areas of dense fibrosis, and honeycombing, and hyperplasia of type II pneumocytes are high suggestive of…
IPF - idiopathic pulmonary fibrosis
What are tx options for IPF?
- Pirfenidone
- antifibrotic agent that inhibits TGF-beta
- nintedanib
- tyrosine kinase inhibitor that inhibits PDGF, FGF, and VEGF
What are endothelin-1 inhibitors and what are they used for?
- ambrisentan and bosentan
- tx idiopathic pulmonary hypertension
Pts with HLA-B*57:01 allele should not take this medication…
why?
abacavir
abacavir hypersensitivity reaction- occurs due to direct binding of drug to a segment of HLA molecule, which alters the presentation of self-peptides to the immune system and results in a delayed hypersensitivity reaction (type IV)
anti-Ro/SSA and anti-La/SSB antibodies are found in pts with
Sjogrens syndrome
Anti-DNA topoisomerase I (Scl 70) antibodies are highly specific for…
systemic sclerosis
the 2 second gen anti-psych meds with highest risk for metabolic syndrome are
olanzapine and clozapine
Dx of hemophilia A and B are made by
measuring plasma levels of factors VIII and IX, respectively
If a pt has a hemophilia, what can be administered to make up for either deficiency?
Thrombin
What does Protein C do?
physiologic anticoagulant that degrades Va and VIIIa
Which strand requires the repetitive action of DNA primase and DNA ligase?
lagging strand synthesis
DNA replication occurs in 5’ to 3’ direction on both strands, leading strand is continuous and lagging strand is discontinuous, occurring in short stretches of RNA primer plus newly synthesized DNA segments
What does metyrapone do/how does it work?
will cause a decrease in cortisol synthesis via inhibition of 11-beta-hydroxylase;
in pt with intact HT-pit-adrenal axis, this will cause a reactive increase in ACTH, 11-deoxycortisol and urinary 17-OH-corticosteroid levels
type of optic neuropathy characterized by atrophy of the optic nerve head - dx?
why does this happen?
where does this come from?
glaucoma
due to increased production or decreased outflow of aqueous humor - increasing IOP
aqueous humor is produced by the epithelial cells of the ciliary body
What will you see on funduscopic exam of gluacoma?
how is it treated?
increased cup to disc ratio due to loss of ganglion cell axons
timolol and other nonselective beta blockers work by diminishing the secretion of aqueous humor by the ciliary epithelium
acetazolamide (carbonic hydrase inhibitor) can do the same;
PGF2a (eg latanoprost, travoprost) and cholinomimetics (pilocarpine, carbachol) decrease IOP by increasing the outflow of aqueous humor
What do reactive lymphocytes look like?
when are they present?
large, scalloped, and have abundant cytoplasm; contain cytotoxic granules composed of perforin and granzymes
they are activated, pathogen specific cytotoxic T cells and NK cells that form in response to certain intracellular infections, esp infectious mononucleosis
elderly pt with any combination of hypercalcemia, normocytic anemia, bone pain, elevated gamma gap, or renal failure
multiple myeloma
renal failure in multiple myeloma is commonly caused by… and presents with
light chain cast nephropathy
large, waxy, eosinophilic casts composed of Bence Jones proteins seen in the tubular lumen
What happens when you perform a carotid sinus massage?
- increased afferent firing from the carotid sinus
- increase vagal parasympathetic tone
- slows conduction through AV node
- prolongs the AV node refractory period
- terminates reentrant tachycardia
- prolongs the AV node refractory period
- slows conduction through AV node
- increase vagal parasympathetic tone
liver appears black due to impaired excretion of epinephrine metabolites that are accumulating in lysosomes
dx?
why?
Dubin-Johnson syndrome
defective hepatic excretion of bilirubin glucuronides due to a mutation in the canalicular membrane transport protein
results in direct (conjugated) hyperbilirubinemia and episodes of jaundice
How is arsenic poisonous?
binds to sulfhydryl groups, impairing cellular respiration via inhibition of pyruvate dehydrogenase and disruption of gluconeogenesis and glutathione metabolism
garlic odor on breath after ingestion of insecticide
dx? tx?
arsenic poisoning
dimercaprol - increases urinary excretion of heavy metals by forming stable, nontoxic soluble chelates
buspirone indication and MOA
Generalized anxiety disorder; non benzo anxiolytic use in tx of GAD with no risk of dependence
slow onset of action (almost 2 weeks), lacks muscle relaxant or anticonvulsant properties
partial agonist of 5-HT1A
What test do you use to monitor warfarin therapy?
what about unfractionated heparin?
warfarin - Prothrombin time (PT)/INR
unfractioned heparin - activated Partial Thromboplastin (aPTT)
INR is…
target value?
international normalized ratio
a ratio of pt’s PT to a control
target for AF is 2.0-3.0
Why are pts with Crohn disease likely to get gallstones?
Crohn disease affects terminal ileum most often, the site of bile acid resorption
without bile acid resorption, it promotes cholesterol supersaturation of the bile, resulting in gallstone formation
What abnormal bone pathology can be seen in CKD?
renal osteodystrophy from secondary hyperparathyroidism (caused by hyperphosphatemia and hypocalcemia)
high turnover osteodystrophy increases bone resorption more than formation, causing osteopenia and pathologic bone changes similar to those seen in primary hyperPTH; can also develop osteomalacia
neonate with chorioretinitis, hydrocephalus, and a placenta infiltrated with intracellular crescent-shaped organisms likely has…
congenital toxoplasmosis
If there is a pre-existing lung cavity in a pt and new onset hemoptysis, what is my concern?
aspergilloma - colonizing form of aspergillus, forming a fungus ball within a preexisting lung cavity
appears on CXR as radiopaque structure that shifts when pt change position
In essential fructosuria/fructokinase deficiency, what enzyme takes over that role and what does it do?
hexokinase takes over the role of fructose metabolism, converting dietary fructose into fructose-6-phosphate to be used in glycolytic pathway or pentose phosphate pathway
MCC of male hypogonadism?
what are features of this disease?
Klinefelter syndrome
- progressive destruction and hyalinization of the seminiferous tubules cause the testes to be small and firm
- serum inhibin levels are decreased as a result of the Sertoli cell damage
- Leydig cells are usually dysfunctional as well, resulting in reduced testosterone levels
- loss of FB inhibition results in elevated FSH and LH
- high estrogen levels and gynecomastia due to increased aromatase activity
hypokalemia in an otherwise healthy young adult with a normal BMI and preoccupation with body shape and weight
dx?
what is another common physical finding?
self-induced vomiting with bulimia nervosa
parotid gland enlargement, tachycardia, hypotension, dry skin, calluses or scarring on the dorsum of the R hand (Russell sign), and erosion of dental enamel
What kind of drugs are likely to cause drug-induced lupus?
drugs metabolized by N-acetylation in the liver (procainamide, hydralazine, isoniazid)
genetically predisposed individuals who are slow acetylators are at greater risk
renal arterioles showing medial hypertrophy and fibrointimal proliferation - what causes this?
hypertensive nephrosclerosis - complication of chronic HTN common in elderly
Why is the Hep C virus genetically unstable?
- lacks proofreading 3’ to 5’ exonuclease activity in its RNA polymerase
- envelope glycoprotein sequences also contain a hypervariable region prone to frequent genetic mutation
What should pts take if they are intolerant to aspirin?
What is the MOA of this drug?
clopidogrel
irreversibly blocks the P2Y(12) component of ADP receptors on the platelet surface and prevents platelet aggregation
PDE inhibitor occasionally used in pts with symptomatic peripheral vascular disease (claudication)
Cilostazol
eptifibatide MOA
platelet glycoprotein IIb/IIIa inhibitor that inhibits the final common pathway of platelet aggregation
for pts with ACS but not stable CHD
MC type of groin hernias in both sexes?
how/why does it occur?
indirect inguinal hernia
usually congenital, d/t failure of the processus vaginalis to obliterate (in males) or of the deep inguinal ring to close (in females)
protrude through the internal inguinal ring, lateral to the inferior epigastric vessles, allowing them to follow the same path as the spermatic cord through the inguinal canal and into the scrotum
what is diastasis rectus abdominis?
characterized by an abnormally large separation between the rectus abdominus muscles due to stretching and laxity of the linea alba
occurs in states with increased intraabdominal pressure (pregnancy or obesity) and characteristically presents with a bulge in the midline around the umbilicus
Who do you normally see femoral hernias in?
occur mainly in older women due to laxity and widening of the femoral ring, which allows abdominal contents to protrude below the inguinal ligament into the femoral canal
What is Bloom syndrome?
- AR disorder caused by mutations in BLM gene
- gene encodes DNA helicase
- dysfunction results in chromosomal instability and breakage and manifests clinically with growth retardation, facial anomalies, photosensitive rash, and immunodeficiency
Why do gamma chains of fetal hemoglobin not bind effectively to 2,3 BPG?
due to replacement of a histidine residue with serine
In bladder outlet obstruction, what are the different components that comprise it and what drugs work on each component?
- dynamic component
- smooth muscle tone in bladder neck, prostate capsule, and prostatic urethra
- alpha-adrenergic antagonists (terazosin, tamsulosin) work quickly to relax smooth muscle
- fixed component
- structural effects of enlarged prostate
- 5-alpha reductase inhibitors (finasteride, dutasteride) over time reduce prostate volume (6-12 mo)
Phenazopyridine indication
urinary analgesic to give symptomatic relief of dysuria in UTI
antimuscarinic to tx overactive bladder symptoms
AE?
tolterodine
urine retention
How does class switching to modify immunoglobulins work?
B cells modify production
occurs by splicing out DNA coding for different types of the heavy chain constant region until desired isotope is reached;
variable region, and therefore antigenic specificity of the antibody, stays the same
How does class swithcing work in regard to T and B cell interaction?
activated CD4 T cell uses its CD40 ligand to bind CD40 on B cell surface
excess thyroid hormone, whether due to endogenous hyperthyroidism or iatrogenic over-replacement with levothyroxine, causes
increased beta-adrenergic receptor expression;
hyperadrenergic state can lead to severe CV complications: HTN, tachycardia, increased myocyte automaticity, AFib, high output heart failure, worsening of angina pectoris
serum calcium >13 mg/dL suggests…
why does this happen?
underlying malignancy
Humoral hypercalcemia of malignancy is MCC of hypercalcemia in pts with malignancy and is due to secretion of PTHrp by malignant cells
Characteristics of PTHrp
- closesly resembles PTH at the bioactive amino-terminal region
- causes increased bone resorption
- decreased renal excretion of calcium
- increased renal excretion of phosphorus (leading to hypophosphatemia)
- does not increase 1,25-dihydroxyvitamin D production
What are clinical features, tx, and complications of cryptorchidism?
- clinical features
- empty scrotum/hemiscrotum
- +/- mass in inguinal canal
- treatment
- orchiopexy before age 1 (sx placement of testes in scrotal sac)
- complications
- decreased fertility
- testicular cancer
- testicular torsion
AE of tetracyclines when used in pregnant mom
tetracyclines localized in the enamel and dentin of developing teeth, causing enamel hypoplasia as well as yellow, gray, or brown staining of the deciduous teeth
if exposure is near term, permanent teeth can also be stained
terbinafine and other allylamines MOA
inhibits synthesis of ergosterol by inhibiting enzyme squalene epoxidase
MOA of caspofungin and echinocandin calls of antifungals
blocks synthesis of Beta (1,3)-D-glucan, a main component of Candida and Aspergillus cell walls
MOA of Griseofulvin
binds to polymerized microtubules and disrupts the fungal mitotic spindle, thus preventing fungal cell mitosis
what stores and releases pulomary surfactant into the fluid layer lining the inner surfaces of alveoli?
lamellar bodies of type II pneumocytes
recurrent sinopulmonary infections and exocrine gland fibrotic atrophy in a young Caucasian are suggestive of
CF
What may contribute to squamous metaplasia of the epithelial lining of pancreatic exocrine ducts?
What does the epithelium become?
Vitamin A deficiency
keratinized
Where does ADH act in the kidney?
acts on the medullary segment of the collecting duct to increase urea and water absorption, allowing for maximally concentrated urine
What does the mutated huntingtin gene do?
transcriptional repression - silencing
causes increased histone deacetylation, silencign the genes necessary for neuronal survival
What do homeodomain/homeobox genes do?
critical for the sequential development of organs and tissues along the body axis during embryogenesis; mutations affecting these genes cause alterations in body structure, leading to congenital malformations or spontaneous abortions
DNA damage by UV light
thymidine dimerization
Rheumatoid factor is an antibody (typically IgM) specific for…
the Fc component of IgG
antiphospholipid abs can be found in pts with…
What do these abs do?
SLE and antiphospholipid antibody syndrome
cause a hypercoaguable state with paraoxical PTT prolongation
What does thyroid peroxidase do?
multifunctional enzyme that catalyzes the oxidation of iodide, the iodination of thyroglobulin, and the coupling reaction between 2 iodized tyrosine residues
Gastric bypass surgery can cause small intestine bacterial overgrowth (SIBO) due to excessive bacterial proliferation in the blind-ended gastroduodenal segment. What can this do to vitamins and other gut substances?
- result in deficiency of most vitamins
- B12, A, D, and E
- and iron
- and zinc due to malabsorption
- increased production of folic acid and vitamin K
What is the major determinant of severity in Tetralogy of Fallot?
degree of RV outflow tract obstruction, major determinant of R to L intracardiac shunting and resulting cyanosis
degree of RVOT obstruction is dynamic and can increase suddenly, leading to profound cyanosis (tet spells)
(VSD is generally large, which allows for equal pressure in RV and LV)
Most likely cause of fever and fatigue with new-onset cardiac murmur is…
What can be a complication of this?
infective endocarditis
diffuse, proliferative glomerulonephritis secondary to circulating immune complex deposition may complicate IE and can result in acute renal insufficiency
Where do ovarian veins drain to?
Ovarian vein thrombosis is more often where?
L ovarian vein drains to L renal vein
R ovarian vein drains directly to IVC
more often R sided, but pulmonary emboli are uncommon and morbidity/mortality is low
medication induced fat redistribution is called…
this is a common AE of…
lipoatrophy or lipodystrophy
highly-active antiretroviral therapy (HAART) and can be considered a product of 2 independent processes: wasting of fat from face and extremities and deposition of fat in the trunk and viscera
subcutaneous lipoatrophy involving the face and extremities is a/w what drugs?
NRTIs (like stavudine and zidovudine) and protease inhibitors
Marker of osteoblast activity
elevated AlkP, and N-terminal propeptide of type 1 procollagen (PINP)
PINP is released during post-translation cleavage of type 1 procolalgen before its assembly into mature type 1 collagen fibrils
Irreversible ischemic injury to the brain tissue causes…
different from other organs that do..
tissue digestion by hydrolytic enzymes (liquefactive necrosis)
the infarcted CNS tissue is eventually replaced with a cystic astroglial scar
other organs with lethal ischemic injury result in coagulative necrosis
Cachexia is driven by what pathways?
hypermetabolic state driven by elevated pro-inflammatory cytokines (TNFa and IL-6), which stimulate ubiquitin-proteasome pathway to degrade skeletal muscle proteins (eg actin and myosin)
during fetal development, testes originate within the…. and establish their arterial supply from the…
thus lymph from the testes drains through lymph channels …
retroperitoneum
abdominal aorta
directly back to the para-aortic (retroperitoneal) lymph nodes
