Random Missed Uworld - Week 4 Flashcards
Complications of long-standing DM:
- Advanced glycosylation end products - refers to the attachment of glucose to AA residues in various proteins forming rev. glycosylation products that slowly stabilize to irreversible products. Glycosylation products accumulate and cross-links with collage in blood vessels and interstitial tissues contributing to microangiopathy and nephropathy. Cross-linking of protens by glycosylation products also facilitates inflammatory cell invasion and deposition of LDL in the vascular walls leading to atherosclerosis
- Polyol pathway - occurs in tissues that do not depend on insulin for glucose transport: lens, peripheral nerves, blood vessels and kidney
intracellylar glucose concentrations –> sorbitol by aldose reductase and sorbitol –> fructose. Both sorbitol and fructose increase osmotic pressure in titusses and stimualte the influx of water leading to osmotic cell injury.
Increased water in lens fiber cells leads to rupture of tehse cells with resultant opacification of the lense and cataract formation. Osmotic injury of schwann cells contributes to peripheral neuropathy in diabetes
“burnt smell sugar”
Maple syrup urine disease!
Autosoma recessive inborn error of metabolism due to branched-chained alpha-ketoacid dehydrogenase complex deficiency - enzyme normally allows for the break down of leucine, isoleucine, valine into substrates to enter the TCA cycle
- (I Love Vermont maple syrup)*
- clinical presentaiton:* neurotoxic primarily due to elevated levels of leucine, infants present in the first few days of life with preogressive irritability, poor feeding, lethary and increased muscle tone
Urine characteristically has a sweet maple syrup odor
dx can be confimed by the presence of elevated brancehd-chained amino acid levels
tx: dietary restriction of branched-chain AA, but pt remian at lifelong risk for neurotoxicity in the setting of intercurrent illnesses and fasting
Negative predictive value (NPV) =
the probability of being free of a disease if the test result is negative - it is important to remember that the NPV will vary with the pretest probability of the disease.
- the prevalence of a disease is directly related to the pre-test probability of having the disease and thus also affects the NPV*
- example- HIV and ELISA test result, pt with high-risk group has a high pre-test probability; consequently, this patient will have a low NPV vs a patietn who belongs to low risk and has a low pre-test probability, will have a high NPV.*
Left vs Right fontal lobe lesions
Frontal lobe - important for executive function and personality, includes the ability to perform complex tasks and includes motivation, organization, planning and purposeful action.
Injury could not only affect work performace and affect but also impair social and emotional behavior with manifestaitons ranging from sexual disinhibition and emotional lability to apathy and depression.
In a right-handed person:
Dominant (Left side)- associated with apathy and depression
Non-dominant (Right side)-associated with disinhibited behavior
Corpus callosum injury
–> split brain syndrome
may appear normal in general social situaitons but further eval can demonstate lack of interhemispheric transfer of info (ie- unable to transfer objects from one hand to the other)
Parietal lobe injury
process and interpret visual, auditory and motor signals received from other brain areas
damage results in difficulties with spatial and visual perception;
Non-dominant parietal lobe lesions (most commonly right-sided) can result in hemi-neglect, constructional apraxia and denial of the problem.
Dominant parietal lobe lesions - (commonly left sided), result in Gerstmann syndrome with right-left confusion and difficulty with writing and mathematics
Temporal lobe lesions
can cause disturbances in language, sensory interpretation and impaired memory
can also exhibit bevioral changes (Kluver-Bucy syndrome - bilateral amygdala)
Non-dom (usually right sided) can affect nonverbal memory, including musical ability
dominant lesions (usually left sided), can affect verbal memory, such as word recognition
What IL stimulates class switching?
IL4 –> class switch to IgG and IgE
IL 5 –> IgA (and activates eosinophils)
Acute serum sickness:
Serum sickness—an immune complex disease in which antibodies (hypersensitivity reaction III) to foreign proteins are produced (takes 5 days). Immune complexes form and are deposited in membranes, where they fix complement (leads to tissue damage).
Most serum sickness is now caused by drugs (not serum) acting as haptens. Deposition of IgG and/or IgM complement-fixing antibodies results in localized complement consumption and hypocomplementemia (ie-decrease serum C3 and C4 levels, and neutropenia due to C5a)
Clinical Pres: Fever, urticaria, arthralgia, proteinuria, lymphadenopathy occur 5–10 days* *after antigen exposure.
–> histo: small vessel vasculitis with fibrinoid necrosis and intense neutrophil infiltration
Think: post-chimeric monoclonal antibody administration (rituximab, infliximab) or nonhuman immunoglobulins (venom antitoxins), nonprotein drugs (penicillin, cefaclor and tmp-smp)
Primary TB infeciton..how could you tell the difference btw primary and secondary?
Primary infection - usually, there is a Ghon complex = lower lobe lung lesion (Ghon focus), accompanied by ipsilateral hilar adenopathy
pulm TB infection is first est. after the gravity-assisted entry of small organisms-laden droplets into the LOWER lobe –> phagocytosed by alveolar macrophages and the sulfatide virulence factor expressed by M. TB a_llows for intracellular bacterial_ proliferation – while nested in the macrophages, M.TB enters the lumphatic circulation, and eventually it can seed organs throughout the body
Immune rxn: Th1 cell-mediated, resulting in caseating necrosis where the organisms are present – caseating granulomas consist of T lymphocytes, epithelioid activated macrophages, Langhans giant cells and proliferating fibroblast that actively synthesize collage –> dormant M. TB bacilli are sitll present within the larger granulomas of many pt able to later casue secondary during periods of immuno supppression
secondary TB is reactivation after a period of incomplete elimination + iummunosuppression –> active diseaes. In the lung, typical patholgic finding associated with secondary infeciton is an apical cavitary lesion
What are the important enzymes and shuttles invovled with the degradation of fatty acids into acetyl coa for energy?
Fatty acid + CoA (faty acid CoA synthase –> using the cartininte shuttlye enters the mitocondira from the cytosol –> fatty Acyl CoA + Acyl CoA dehydrogenases B oxidation enzme –> acyl coa –> becomes either ketone bodies or can enter the TCA cycle
When a person has hypoketotic hypoglycemia after a period of fasting – fatty acid B-oxidation in the mito deficiency.
Most common enzyme defect leading to impaired B-oxidation is acyl-CoA dehydrogenase deficiency
Normally b-oxidation of fatty acids yields FADH1 and NADH for ATP production and generates acetyl-CoA for the citric acid cycle and ketone bodies…during periods of fasting, pt with acyl-CoA deficiency cannot oxidize FA for energy or produce ketone bodies – hypoetotic hypoglycemia.
Pt could be asymptomatic until they experience significant fast
tx: avoid prolong fasting and supply glucose during periods of illness
What does the mullerian tract give rise to?
Female repro tract development invovled the lateral/verticle fusion and involution of the paramesonephric ducts (ie -mullerian ducts) –> fallopian tubes, uterus, cervix and upper vagina.
Development of the paramesonephric and mesonephric ducts is closely linked, thus uterine anomalies often coexist with renal anomalies.
Failed lateral fusion of the paramesonephric duct can result in various anomalies
incomplete* lateral fusion of the upper seg –> bicornuate uterus characterized by an indentation in the center of the fundus (has abnormal contour to teh uterine fundus). *Complete lack of fusion can lead to uterine didelphys (double uterus and cervix
Failed involution of the paramesonephric ducts can result in a longitudinal uterine septum
scren for when there is difficulty conceiving or recurrent pregnancy loss
hysterosalpingogram (contrast) with concurrent pelvic x-ray
complete agenesis of paramesonephric –> Mayer-Rokitansky-kuster-hauser sydnrome = infertility due to blind vaginal pouch and lack of mullerian structures (lower vagina originates from the urogenital sinus)
mesonephric ducts = wolffian ducts = gartner ducts
how does pCO2 affect cerebral vasculature?
How can oxygen demand of the brain be changed?
pCO2 is a potent vasodilator of cerebral vasculature.
Tachypnea –>HYPOcapnia = low pCO2 = cebreral VASOCONSTRICTION–> decrease cerebral blood flow decrease intracranial pressure (desired with high ICP situations, ie - cerebral edema)
brain oxygen demand is reduced via induced sedation and therapeutic hypothermia –> decrease metabolic demand, exerting a neuroprotective effect and improving ICP by reducing cerebral blood flow
What are the main factors influencing cerebral circulation?
Systemic blood pressure and arterial blood gas levels
@ 60-140 mmHg, systemic BP has little effect on cerebral blood flow because autoregulation (via cerebral blood vessel dilation and contraction) keeps blood flow constant
>150 mm Hg –> increased cerebral flow, inc ICP
<50 mmHg will cause hypoperfusion and potential cerebral ishcemia
Arterial blood gasses have a powerful effect on cerebral blood flow with pCO2 being the most imporant regulator
Drop in pCO2 due to hyperventilation casues vasoconstriction, increasing vascular resistance and reducing cerebral blood flow
Lowering pCO2 is one of hte measures employed to reduce ICP in mechanically ventilated pt with cerebral edema
Dx of Strongyloides stercoralis?
Rhabditiform larvae in the stool
infection is transmitted by filariform/infectious larvae found in soil contaminated with human feces; the larvae penetrate teh skin and migrate hematogenously to hte lungs –> enter the alveoli and travel up the bronchial tree to the pharynx, where they are swallowed…the larvae reach teh intestines, develop into adults that lay eggs within the intestinal mucosa –? hatch into rhaditiform/noninfectious larvae that migrate into the itnestinal umen to be excreted in teh stool
some rhabditiform larvae can molt directly into filariform larva withiin the intestine and re-infect the host by enetratin the intestinal wall or perianal skil = autoinfection; massive increase in worm burden leading to widespread disseminaiton of the parasites thorugh the body = hyperinfection
–> multiorgan dysfunction and septic shock
this occurs more often in pt taking immunosuppresants or with HTLV-1 infction; impaired Th2 directed cellular immunity
Occurs more commonly in tropical and warm temperate regions particularly southeast asia. Most pt are asymptomatic but some present with chronic intermitten GI or pulmonary sx. Pruritic, erythematous, linear streaks known as larva currens may occur on the thigs and buttocks as the larva migrate subcutaneously away from teh perianal region.
dx: larva in stool
egss and adult parasites only seen in intestinal biopsy
tx: ivermectin
Efficacy vs potency of a drug:
Efficacy is a measure of the max pharmacodynamic effect avhievable with a drug
Potency refers to the dose of durg that is required to produce a given effect; drugs that bind their receptors with a higher affinity or are better able to gain access to their target tissue wil have a greater potency (lower ED50=dose required to produce half of the max biological response, same efficacy at a lower dose), the lower the ED50, the more potent.
What is the classic triad of bacterial meningitis?
Fever, stiff neck, altered mental status
Requires promt blood cultures, empiric antibiotics and lumbar puncture w/ CSF analysis to confirm diagnoiss, identifying the offending organism and determine antibiotic susceptibility
How is isoniazid metabolized and what phenomenon could be seen with this rxn?
Isoniazid is metabolized by acetylation.
The speed with which a pt is able to acetylate drugs depends on whether they are generally fast or slow acetylators –> results in a bimodal distribution of the speed of isonizid metabolism. SLow acetylators are at increased risk for adverse effects.
will have a bimodal distribution
other drugs that are acetylated: dapsone, hydralazine, procainamide
What is linkage disequilibrium?
When a pair of alleles from two loci are inherited together in the same gamete/haplotype more or less often than would be expected by random chance alone give their corresponding allele frequencies
DoesNOT always imply physical proximity between allelic loci, although linkage disequilibrium can be the result of physical linkage of genes on teh same chrom it can also occur even if the genes are on different chromosomes dur to mutations, genetic drift, migration, selection pressure and non-random mating.
to estimate the prob of two alleles appearing together, multiply their occurence
Mitral stenosis-
hemodynamic changes and heart sounds
loud first heart sound, early diastolic opening snap after teh second heart sound and a low-pitch diastolic rumble, best heard at teh cardiac apex using the bell of the stethoscope withe the pt lying on the left side in held expiration
Hemodynamic tracings in pt with mitral stenosis typically reveal an elevated pressure gradient between the left atrial and left ventricular end-diastolic pressure
Left ventircular pressure falls rapildy during isovolumetric relaxation –> oepning snap, by the suddne opening of the mitral valve leaflets when the left ventricular diastolic presusre falls below the left atrial pressure at the beg. of diastole
As the mitral stenosis becomes more severe, the opening snap occurs earlier after S2
What is akathisia?
Subjective restlessness with inability to sit still
could be induced by anti-psychotic treatment
may be misinterpreted as worsening psychotic beahvior and agitation
tx: decreasing the anti-psychotic dose if feasible or treating with a beta blocker or benzo
What are some side effects of anti-psychotic tx?
1. extrapyramidl side effects - acute dystonic reaction (sudden onset of sustained muscle contraction), akathisia*, *drug-induced parkinsonism (tremor, rigidity, bradykinesia, masked facies)
2. Tardive dyskinesia - involuntary movements after chronic use (lip smacking, choreathetoid movements); could be irreversible, due to prolonged antipsychotic exposure (years).
3. Neuroleptic malignant syndrome -acute; fever, rigidity, mental status changes, autonomic instability; results from disordered thermoregulation and skeletal muscle metabolism mediated via central mechanisms. Patients present with hyperthermia, extreme generalized rigidity..
Post-strep glomerulonephritis…what is seen in IF microscopy?
Occurs most frequently in children and presents with nephritic syndrome, following recent skin infection.
Light microscopy- enlarged, diffusely hypercellular glomeruli due to leukocyte infiltration (neutrophils and monocytes) and mesangial and endothelial cell proliferation.
Immunofluoresence microscopy shows granular deposits of IgG, IgM and C3 in the mesangium and basement membranes – starry sky appearance
Lumpy bumpy = deposition of antige-antibody complexes at the epithelial surface.
Studies shows decreased serum complement (C3), elevated titers of streptococcal antibodies (anti-DNAase B, anti-hyaluronidase, anti-streptolysin O)
most children recoer with supportive care withouth any long-term sequale
How does teh toxin of tetanus work?
C tetani causes dz not through invasion but by the production of a potent METALLOPROTEASE exotoxin = tetanospasmin
Toxin binds to receptors on the presynaptic membrane of peripheral motor neurons –> migrates by retrograde axonal transprot to central inhibitory neurons in the spinal cord and brian stem and prevents release of inhibitory NT glycine and GABA –> suppression of inhibitory nerve activity = increased activation of motor nerves causing muscle spasms and hyperreflexia
Classic features include difficulty openign jam (lockjaw, trismus) fixed sardonic smile (risus sardonicus) and contraction of back muscles resulting in backward arching (opisthotonos)
Pt are also extremely irritable and develop tetanic spasm in response to minor stimuli such as loud noises
What are the different phases where ovum development is arrested?
Female gametogenesis begins in utero at ~4 weeks gestation when primordial germ cells migrate from teh yolk sac region to the developing gonadal region - tehse germ cells then differentiate into oogonia and multiply by mitosis before begining meiosis I –> Primary oocytes
Primary oocytes are competely developed in female embryos by the 5th month of gestation, at which point they are arrested in PROPHASE of MEIOSIS I, remain here until ovulation
Normal mentrual cycle hormoens stimulate the primary oocyte to resume differentiation –> during each menstrual cycle, FSH stimulation follwed by an LH surg causes some oocytes to resume meiosis I–> secondary oocytes….the secondary oocytes begins meiosis II but halts….36 hours after LH levels being to rise, secondary oocyte is released from the ovarian follicle ….prior to fertilization, secondary oocytes are arrested in METAPHASE of MEIOSIS II…until fertilization in which it completes its division into a mature oocyte/ovum (and second polary body).
What is an axonal reaction?
wallerian degeneration occurs in teh segment of axon that has lost connection with the cell body - it represents the degeneration of axon and myelin distal to the point of injury:
1- swelling and irregularity are noted in the distal segment of the axon
2 - axon is destroyed within a week and fragments digested by schwann cells and macrophages
Similar degenerative changes occur in teh seg of axon that lies proximal to the injury – extends to the closest node of ranvier.
Changes seen in the neuronal body after the axon is severed are called axonal reaction.
- cell body shows signs of cellular edema, becomes swollen and rounded, with the nucleus displaced to the periphery
- Nissl substance becomes fin, granular and dispered throughout the cytoplasm (central chromatolysis)
becomes visible 24-48 hours after the injury; maximal chianges in teh neuronal body occur apx 12 days after the injry - reflect an increased synthesis of protein by the cells in order to regenerate the severed axon
Succinylcholine AEs
Succinylcholine is a depolarizing neuromuscular-blocking agent that like acetylcholine attaches to the nicotinic acetylchonie receptor and depolarizes the NM end plate; not degraded by acetylcholinesterase –> continuous stimulation of the endplate (initial transiet fasciculations) –> inactivate sodium channels and cannot reopen until the end plate is repolarized
remaines isolated to the end plate resulting in development of flaccid paralysis (phase 1 block) – evetually with continuous administration, the continuous depolarization of the end plate gives way to gradula repolarization as the nAChR becomes desensitized to the effects of succinylcholine –> phase II block, similar to non-depolarizing blokade.
Malignant hyperthermia (esp with halothane) in genetically susceptible pt
Severe hyperkalemia in pt with burns, myopathies, crush injuries and denervation (because of upregulation of muscle nAChRs
Bradycardia from parasympathetic stimulaiton or tachycardia from sympathetic effects
H2O absorption and permeability in the neprhon:
The proximal tubule reabsorbs >60% of the water filtered by the glomeruli, regardless of the patient’s hydration status. This water is absorbed isosmotically with solutes.
NO concentration or dilution of the urine occurs in this segment
In dehydrated state: plasma osmo increases, ADH is released, allowing for improved water permeability in teh collecting ducts, allowing production of maximally concentrated urine (osmo 1200)
No water is reabsorbed in cortical collecting duct, distal tubule or medullary collecting duct in overhydrated state; up to 20% of original filtered urine can be reabsorbed with ADH in dehydrated state
Descending loop of henle absorbes about 20% of filtered water
** highest osmolarity at the bottom of the loop of henle!
MOA of Ezetimibe:
Decreases intestinal absorption of cholesterol by inhibiting the Niemann-Pick C1-like 1 transporter protein, which transports dietary cholesterol from teh GI lumen into teh intestinal enterocytes – less cholesterol reaches teh liver, lowering intrahepatic cholesterol levels –> liver increases LDL receptor expression, whcih draws cholesterol out of circulation
psoas muscle:
originates from teh anterior surface of the transvers processes and lateral surface of the vertebral bodies at T12 - L5
Inferiorly (at around the level of the inferior ligament), the psoas muscle combines with the iliacus muscle –> iliospoas muscle, which functions with hip flexion, also contributes somewhat to lateral rotation and abduction of the thigh
*HIV, IV drug use and diabetes are risk factors for primary psoas abscess development
what are the most common pathogens causing nosocomial bloodstream infections?
Coag-neg staph
staph aureus
enterococci
candida spp
monitor for new-onset fever or bacteremia
first-gen cephalosproin used as it provides good coverage agasint much of the normal skin flora.
Wernicke encephalopathy:
Chronic alcohol users are malnourished and have low levels of thiamine at baselin.
IV dextrose admin withouth prior thiamine supplementaiton in these patietns results in an acute drop of thiamine levesl –> wernicke encephalopathy
Clincal pres: ataxia, nystagmus, opthamoplegia, anterograde amnesia (CAN - confusion, ataxia nystagmus)
Chronic effects of thiamine deficiency can lead to Korsakoff psychosis = anterograde and retrograde amnesia, apathy, lack of insight and confabulation
*Thiamine is a key coenzyme for pyruvate dehydrogenase, which is invovled in glucose metabolism – thus deficiency results in the brains inability to metabolize glucose –> energy
Teh structure of the brain that most frequently undergoes necrosis in the setting of thiamine deficiency is the mammillary body ( part of the papez circuit, which is a neural pathway of the limbic sys tha tis invoved in teh cortical control of emotion and meory)
What medications are associated with osteoporotic fractures:
- Anti-convulsants that induce CYP 450 (phenobarbital, phenytoin, carbamazepine)
- Aromatase inhibitors
- Medroxyprogesterone
- GnRH agonist (dec T and E)
- Proton pump inhibitors (dec calcium absorption- insoluble calcium req an acidic environment for proper absorption and acid-suppressing meds can interfer with the process)
- Glucocorticoids
- Unfractionated heparin
- Thiazolidinediones
What pathway does phosphoinositol second messanger use?
System begins with ligand-receptor binding and Gq protein activation leading to activation of phospholipase C (PLC). PLC then hydrolyzes phosphatidyl inositol bisphosphate and froms diacylglycerol and inositol triphosphate IP3. Finally, IP3 activates protein kinase C via an increase in intraceullar calcium
Osteonecoriss?
avascular necrosis of the bone due to impaired blood supply to a segment of bone.
The femoral head is the most common location, although other bones may be affected
Associated conditions:
- SCD leads to thormbotic occlusions of arteries, embolic occlusions (fat emboli, decompression sickness) can also cause osteonecrosis
- injury to the vessel wall, vasculitis, causes impaired blood supply (sle)
- high dose corticosteriod therapy and alcoholism are also associated with ostenecrosis of the femoral heald although the mechanism is unknow
presents iwth chronic, progressive groin and hip pain that is exacerbated by wt bearing. Physical examinaiton reelas restricted movement in teh affected joint with no swelling, erythema or warmth in the surroudnign area. Microscopic analysis of the wedge shaped zone of the affected bone is notable for dead bony trabeculae/empty lacuna and fat necoriss
How does the kidney respond to hypoxia?
Peritubular cells in teh renal cortex sense hypoxia and respon by releasing erythropoietin into the bloodstream (deficient erythropoietin production is the reason why many pt with chronic kidney disease develop anemia)
Erythro –> stimualtes erythrocyte production by binding erythro R on erythrocyte precursors in the bone marrow; this response is secondary polycythemia that occurs in pt with chronic hypoxia secondary to:
OSA, COPD, R-to-L shunts and high altitude
[LIVER is major site of erythropoietin production in teh FETUS!]
Ulnar nerve:
branch of hte mdial cord of the brachial pleuxs (C8-T1), that courses posteromedially in the upper arm
Then passes posterior to the medial epicondyle of the humerous to enter the anterior compartment of the forearm – it innervates the flexor carpi ulnaris and the medial portion of the flexor digitorum profundus
At the wrist, nerve passes between the hook of hte hamate and the pisiform bone within Guyon’s canal – then divides into the superficial branch that provdies sensation over the medial 1.5 digits and ypothenar eminence
and a deep motor branch that supplies most of the intrisic muscles of hte nad
Ulnar nerve is the most commonly injured at the elbow - funny bone due to trauma (eg medial epicondyle fracutre) or nerve compression (resting on a hard surface) – presents with loss of sensation/parethesia in the ulnar distribution.
Severe cases can result in weakness of wrist flexion/adduction, finger abduction/adduction and flexion of the 4th and 5th digits
weakness of lumbricals in teh 4th and 5th fingeres may produce ulnar claw hand deformity during finger extension
Focal necrosis crescent fromation..what glomerular disease does this describe?
What would be visible on light microscopy and IF?
Rapidly Progressive Glomeurlonephritis
LM: crescent moon shape (diagnostic!!)
IF: firbin and plasma proteins (C3..)
* Deposition of FIBRIN is essential pathologic step in crescent formation
*Crescent in RPGN consists of proliferated glomerula parietal cells, monocytes and macrophages that have migrated into Bowman’s space + abundant fibrin between the cellular layers of the cresants
*Dz progression: cresants become sclerotic and oblierate Bowman’s space –> decreasing glomerular function
Bad prognosis
This could have been a complication of several disease processes include: Goodpastures, Granulomatosis with polyangiits (Wegners) and microscopic polyangiits
How do the crescents form in RPGN?
macrophages and T cells pass through the gaps into Bowman’s space –> leakage of fibrin into the space as welll
–> damage to glomerular capillaries casues gaps to form in the basement membrane
Promientn fibrin deposition leads to proliferation of parietal cells
Macrophages secrete factors that enhance fibrin deposition, cellular proliferation and fibrosis
Recruitment of interstitial fibroblast that proliferate and secrete collage
What is the difference between ture and false diverticula?
What is Meckel’s diverticula?
True - contains all three parts of the intestinal wall: mucosa, submucosa and muscularis
False- contains only the mucosa and submucosa; usually herniation through defects in the muscular layer; exacmples: Colonic and Zenker (upper esopho) are examples of false/pulsion diverticula.
Meckel’s is a TRUE diverticular (rule of 2’s) -during early embryogen, the lumen of the midgut and yolk sac cavity are connected via the omphalomesenteric/vitelline duct, which should obilerate during the 7th week of fetal life; partial failure of this duct to oblierate –> Meckel’s.
*recall that Mecke’s diver, could contain ectopic tissue (gastric being the most common, second to pancreatic) which can lead to increased gastric acid = ulceration of adjacent mucosa and lower GI bleed (melena/hematochezia)
What are ventricular arrhythmias?
When are they most frequently seen after an MI?
Ventricular premature beats, V.Tac, VFib
Common in the first 24-48 hours after MI
premature or nonstustain arrhythmias do not req. specific therapy vs sustained and recurrent arrythimias are often managed with antiarrhythmic drugs
Drug of choice: AMIODARONE, lidocaine (2nd)
How do class IB drugs work?
Weakest sodium channel blockers, dissociate the fastest
Negligle effect on QRS duration in normal cardiac tissue
Predom bind to sodium channels in their inactivated state
Since ishcemic myocardium has higher than normal resting membrane potential (delaying VG-recovery of sodium channels from their inactivated to resting state), this allows binding of 1B agents to be highly efficacious in inhibiting ischemia-induced ventricular arrythmias
What 4 diseases predispose a person to nephrolithasis?
What dietary intake could predispose to nephrolithasis?
Primary hyperparathyroidism –> hypercalciuria
Crohns Disease –> hyperoxaluria
Distal Renta Tubular Necrosis –> hypocitraturia
Gout –> hyperuricosuria
**Urine supersaturation- main reason for underlying renal stone formation**
Low fluid (dehydration), low calcium, high oxalate (spinach, rhubarb), high protein, high sodium, high fructose
**Calcium stones (ca-oxalate > ca-phosphate) account for 70-80% of all renal stones
What are the 3 main drugs used for kidney transplant rejection prophylaxis and their MOA?
Sirolimus - proliferation signal inhibitor; bin_ds to the immunophilin FK506 binding protein_, forming a complex that inhibits mTOR –> interruption of IL2 signal transduction, preventing G1 to S phase progression* *and lymphocyte proliferation
Daclizumab, basiliximab - monoantibodies that block IL2R
what causes the fishy odor of a bacterial vaginosis infection?
Caused by volatilization of amines produced by G vaginalis and other anaerobes
BV treatment: metronixazole and clindamycin
What enzyme is elevated that could be indicative of HCC?
INC alpha-fetoprotein levels is a typical presentation of HCC, strongl associated with HBV infection
It is thought that the integration of viral DNA into the cellular genome of the host is what triggers neoplastic change from HBV infection –> HCC
viral protein HBx activates teh syntehsis of insulin-like frowth factor II and receptors for insulin like-growth facto I –> stimulating cell proliferation
HBV gene products also suppress p53 tumor suppressor / cell cycle regulatory gene in host cells
Chronic inflammation adn regeneration induced by HBV infection also can facilitate accumulation of mutations in hepatocytes leading to carcinogeneis
ALL THESE EVENTS RESULT FROM INTEGRATIN OF THE VIRAL GENOME INTO HOST CELL
Pyruvate Kinase deficiency..
How does this affect the spleen?
Pyruvate Kinase is the enzyme used in glycolysis to convert phosphoenolypyruvate to pyruvate –> ATP production (since mature RBC do not contain mitochondria, rely on lactate as their main metabolite for glycolysis)
Most ATP produced is used for the transport of cations against a concentration gradient in the RBC
A deficiency in pyruvate kinase –> insufficient ATP production –> disruption of the gradient –> water and potassium loss –> defective maintenance of membrane architecture/echinocyte formation and hemolysis
Reticuloendothelial cells in the splenic red pulp are invovled in teh removal of damanged RBCs–> there needs to be an increase in their activty –> hyperplasia and splenomegaly!
What is pus and what leads to its formation?
Pus = thin, protein-rich fluid known as liquor puris, dead leukocytes, primarily neutrophils
during an infection, macrophages and surrouding endothelial cells release cytokines such as IL8 that trigger neutrophil to enter the site of infection via chemotaxis
IL 8 also induces phagocytosis in neutrophils once they have arrived
Other significant chemotaxic agents = n-formylated peptides, leukotrienes B4, 5-HETE (lekotriene precursor) and complement component C5a (NOT C3a- which recruits and activate eosinohpils and basophils but not neutrophils!)
How does a carotid sinus massage work?
leads to an increase in parasympathetic tone causing temp inhibition of SA node activity –> slowing of conduction through the AV node –> prolongation of the AVe node refractory period. It is useful vagal maneuver for the termination of paroxysmal supraventricular tachycardia (and decrease systemic vascular resistance)
Other vagal maneuvers - valsalva, cold water immersion; all can be used to acutely terminate PSVT (likely due to reentrant impulse treavleing circularly btw slow and rapid conducting segments of teh AV node)
When it does NOT function -
What are NE effect on sympathetic NS?
NE = adrenergic agonist
mostly affects alpha 1, alpha 2 and beta 1 receptors (hardly beta2)
“qiss”
Alpha 1 –> increase IP3 –> peripheral vasoconstriction of skin and viscera –> inc in systolic and diastolic BP with decrease in renal and hepatic blood flow
Alpha 2 –> decrease in cAMP –> dec release of NE and insulin
Beta 1 –> increase in cAMP via Gs –> increased contractility –> increased cardiac contractility, conduction and heart rate (positive chronotropic effect) BUT the HR is opposed by baroreceptor-mediated refelx bradycardia that occurs following the increase in peripheral resistance –> unchanged HR or slight decrease
What is the difference between somatic symptom disorder and conversion disorder?
Somatic Symptom disroder is excessive anxiety and preoccupation with one or more unexplained symptoms
Conversion disorder (aka- functional neurological symptom disorder) is neurologic symptom incompatible with any known neurologic disease; often acute onset associated wtih stress. It is a type of somatic symptom disrer b tit is specifcially characterized by symptoms or deficits of voluntary motor and or sensory function that are INCOMPATIBLE with any recognized neurological condition, cannot be explained by another medical or mental disorder
What is C1 inhibitor deficiency
Pt with recurrent episdoes of abdominal pain, episodes of facial swelling –> angioedema due to C1 inhibitor deficiency (C1INH)
C1INH prevents C1-mediates cleave of C2 and C4, thereby limiting the activation of complement cascade
It also blocks kallikrein-induced conversion of kininogen to bradykinin, a potent vasodilator that also causes increased vascular permeability (–> bradykinin-associated angioedema)
sx: facial swelling without urticaria, life-threatening laryngeal edema and GI manifestations (n/v, colicky pain, diarrhea)
Managemetn of acute attackes invoveld supportive care and the administration of C1INH concetrate or a kallikrein inhibitor
Cocaine withdrawl sx?
depression, fatigue, hypersomnia, hyperphagia, vivid dreams, intense psychomotor retardation, “crash”
There are no significant physical findings with cocaine withdrawals (no change to eyes, seizures, HR…) that is in contrast to opiates (dialted pupils, yawning, piloerection, lacrimation, hyperactive bowel sounds), and alcohol + benzos (seizures, tachycardia, palpitaitons)
What does EBV bind to?
ENV envelop glycoprotein gp350 binds to CD21 (aka CR2), the cellular receptor for C3d complement component.
CD21 is normally present on the surface of B cells (CD19-positive cells) and nasopharyngeal epithelial cells
Why is HBV infection needed for the hepatits D virus to infect?
Hepatitis D = Delta agent
35nm double-shelled particle that resembles teh Dane particle of hepatitis B (HBV)
internal polype assembly of HDV is designated hepatitis D antigen, associated with this antigen is a very short, circular molecule of SS RNA
HDAg is considered replication defective as it must be coated by the external coat hepatitis B surface antigen of HBV to penetrate the hepatocyte; HBV helps coat the viral particles
–> HDV infection can arise either as an acute co-infection with HBV or as a superinfection of a chronic HBV carrier (super is worse!)
**the Hep B surface antigen of HBV must coat the hep D antigen of HDV before it can infect hepatocytes and multiply.
How does CHF exacerbate itself?
HF results in stimulation of the sympathetic NS and teh RAAS in an attempt to maintain effective intravascular volume – inactive angiotensin I is converted into active angiotensin II by endothelial bound ACE in the lungs (predominately the pulmonary vasculature!!)
What would the following lesions result int?
Base of pons -
Caudate nucleus -
Frontal cortex -
Posterior limb of the internal capsule-
Ventral posterior thalamus -
Base of pons - contalateral weakness, ataxia due to involvement of descending motor tracts and pontocerebellar fibers
Caudate nucleus - behaviorn abnormalities, speech/language disturbances and movement disorders
Frontal cortex - social disinhibition and deficts in attention, executive function
Posterior limb of the internal capsule- anterior 2/3 of the posterior lim is mainly composed of motor fibers, psoterior 1/3 contains sensory - rare for it to be soley sensory;more common a combined sensorimotor deficit
Ventral posterior thalamus - hemisensory loss usually is from a thalamic stroke; VPL receives input from teh STT and DCT, and the ventral posterior medial nucleus [damage may result in complete contralateral sensory loss; severe proprioceptive defects may cause unsteady gait]
Lacunar strokes…
location?
cause?
Lacunes are small cavitary infarcts located within the basal ganglia, posterior limb of hte internal capsule, pons and cerebellum.
The infarcts result from occlusion of the small penetrating arteries that supply these deep brain structures (leticulostriate arteries), most commonly in the setting of chronic uncontrolled HTN or diabetes
lipohyalinosis and microatheromas are believed to be the primary cause of lacunar infarcts
Lipohyalinosis - secondary to leakage of plasma proteins through damaged endothelium and is characterized by hyaline thickening of the vascular wall, collageous sclerosis and accumulaiton of mural foamy macrophages
Microatheromas result from atheroscleorotic accumulation of lipid-laden macrophages within the intimal layer of a penetrating artery near its origin of the presnte vessel
These changes predispose to small vessel occlusion adn infarciton of CNS with liquefactive necrosis and the formation of a fluid-filled vacity
do missense or nonsense mutatons affect the protein size? mRNA?
Missense mutaitons are characterized by base substituations that result in the placement of an incorrect AA in the protein sequence - these mutations occur within the coding region of a gene and affect protein translation. The mRNA transcription seize would be unaffected, so the mRNA template would be normal in length
Nonsense mutations introduce a premature stop codon within the coding region –> formation of truncated proteins. A nonsense mutation would not alter the mRNA size though as it only affects protien translation and not transcription.
**careful in whether they are talking about transcription/mRNA or tranlsation/protein production
tRNA:
form of non-coding RNA, specific tRNA transfer certain AA residues to the growth polypeptide during translation
tRNA functions by recognizing the 3 base codon on the mRNA being translated through its anticodon region, which contains the complementary bases; the secondary structure of tNA resembles a cloverleat that contains-
acceptor stem (5’ termina to 3’ termiina NT that includes a CCA tail with the amino acid bound to the 3’ terminal hydroxyl group when teh tRNA is loaded with the appropriate AAA by aminoacy tRNA synthase
3’CCA tail is added posttranscriptionally, helpes to recognize as tRNA molecule; serves as teh amino acid binidng site! aminoacyl tRNA synthetase is the enzyme responsible for “loading” the appropriate amino acid to the 3’ terminal hydroxyl group of the CCA tail
clinical features of vitamin A deficiency -
Night blindness!!
Severe eye dryness adn CORNEAL ULCERATION
keratinization of the skin
growth retardation
immune impairment
causes: insufficient dietary intake, pancreatic insufficiency (chronic pancreatitis, CF), cholestatic liver disease/biliary obstruction (PBC), intestinal malabsorption (inflammatory bowel disease, bariatric surgery, Crohn dz)
Mechanical complication of acute MI:
@ acute, day 3-5, day 5-14
Acute: Right ventricular failure –> hypotension, clear lungs, kussmaul sign
ventricular arrhythmias (Vfib) are the most common cause of sudden cardiac death within the first 48-72 hours after MI
Day 3-5: Papillary muscle rupture –> acute, severe pulmonary edema; severe mitral regur with flail leaflet
Interventricular septum rupture/defect – new holosystolic murmu, stepped up oxygen level btw right atrium and ventricle
Day 5-14: free wall rupture [sx: suddent onset of chest pain, profound shock and rapid progression to death; rupture appears as a slit-like tear in the infarcted myocardium with a preference for the left ventricle due to higher systolic pressures] hemopericardium and cardiac tamponade
What is the POWER OF A STUDY and how is it calculated?
Power of a study is the ability to detect a difference between groups when such a difference truly exists.
Power is related to type II error (B) = probabilty of concluding there is no difference between groups when one truly exists
Power = 1-B
Type 1 error = probability of seeing a difference when tehre is no difference in reality.
What are common treatments for ACUTE migraines
for migrain prophylaxis?
Acute migraines –> TRIPTANS = serotonin 5HT1n/5HT1D agonist used as abortive therapy during an acute migraine
For prophylaxis: beta-blockers, anti-Ds (amitriptyline, venlafaxine) and anticonvulsants (valproate, topiramate) are common used for migraine prophylaxis
What artery is most likely be affected by a posterior duodenal ulcer
gastroduodenal artery
This artery arises from teh common hepatic artery and perfused both the pylorus adn the proximal part of the duodenum
@ the anterior of the dudoenum, an ulcer is more likely to perforate
How do you calculate the bioavailability of a drug?
Bioavailability = the fraction of administered drug that reaches teh systemic circulation in a chemically unchanged form. Bioavailability for a drug administered by a non-IV route is always less than 1. IT can be determined by examining a graph of plasma concentration versus time and then applyin the formula:
F= (AUC oral x dose IV) / (AUC IV X oral dose)
bioavailability for IV is 1. so you pust divide the AUC for whatever route by the bioavailability of the IV.
Positive Anti-histone ab and
Positive Anti-nuclear ab?
Anti-histone refers to drug induced lupus
and anti-nuclear is also another either non-specific antibody or seen in SLE. (maybe anti-dsDNA but rarely seen since this is more specific for SLE)
Clinical sx: abrupt onset symptoms - fever/fatigue, arthralgias/arthritis, rash, serositis
*predilection for slow acetylators
Implicated drugs: SHIPPE
Hydralazine
Isoniazid
Procainamide
phenyotin
etanercept (TNF-alpha inhibitors)
Minocycline
- usually clinical improvement is rapid on discontinuation of the caustive agent*
- Procainamide, hydralaizine and isoniazid are metabolized via phase II acetylation in the liver*
Patients that are slow acetylators are alos predisposed to isoniazid-induced peripheral neuropathy due to increased drug concentrations
What is one common side effect that many of the anti-psychotics share, especially risperidone?
Risperidone is an anti-psychotic drug that is used in the management of schizophrenia.
Its primary action is to inhibit dopamine D1 and D2 receptors and also inhibits serotonergic and alpha-adrenergic pathways
Since the secretion of prolactin is controlled by the inhibitory effect of hypothalamic dopamine–> drug induced hyperprolactinemia by blocking D2 receptors on lactotrophs. Elevated rolactin leads to amenorrhea (inhibition of GRHR), galactorrhea and breast soreness due to the loss of normal tonic ihbition of prolactin release by dopamine.
SERMS
selective estrogen receptor modulators = competitively inhibit estrogen binding; mixed agonist/anatgonist action
Tamoxifen – adjuvant tx of breast CA; treatment for estrogen receptor- positive BCA
Raloxifene – + also postmenopausal osteoporosis; excellent for prevention
AEs: hot flashes, venous thromboembolism, endometrial hyperplasia and CA (tamoxifen only)
Name the lymphoma:
Bone marrow smear shows numerous lymphocytes with high N/C ratio and mixture of clefted noncleaved nuclei
pt presents with:long, waxing and waning course, is middle aged with painless lymph node enlargement (or abdominal discomfort from an abdominal mass)
Follicular lymphoma!
majority exhibit t(14,18)
overexpression of bcl-2 oncogene that blocks programmed cell death
most common indolent non-hodgkins lymphoma in adults and second most common NHL overall
What is the pathogenesis behind superior mescenteric artery?
What could be affected?
SMA leaves the aorta at L1…normally, the angle is about 45 degrees.
If this angle is dimished to less than 20 degrees than teh TRANSVERSE portion of the duodenum can get entrapped between the SMA and aorta –> sx of small bowel obstruction.
This can occur with any condition that causes diminished mesenteric fat, including low body weight, recent weight loss, severe burns or other inducers of catabolism and prolonged bed rest
It can also occur with pronounced lordosis or after surgical correction of scoliosis, as this procedure lengthes the spine resulting in decreased mobility of the SMA
Non-pharmacologic treatments for insomnia include:
sleep hygiene (reg sleep schedule, avoid naps, avoid caffeine after lungh, avoid alcohol smoking largem emals…adjust bedroom to enviornment, exercise regularly but not soon before bed)
Stimulus control (only bed for sleep and sexual acvitivity!! if you can’t sleep leave and go to another room; fixed wake up time including weekend)
relaxation
sleep resitriction
What does PAS stain?
Periodic acid-schiff reaction is used in histochemical staining because the periodic acid oxidizes carbon-carbon bonds, forming aldehydes that produce a brilliant magenta color upon reacting with the fuchsin-sulfurous acid.
Particuarly effective at highlighting polysac of the funal cell wall, mucosubstances secreted by epithelia, and basement membranes
glycoprotein present in teh cell walss of gramp-positive actinomycete T. whippelii appears magenta + diastase-resistance
What branch is usually associated injury to the inferior wall of the heart?
in 90% of individuals, the posterior inferior wall of the left ventricle is supplied by teh posterior descending branch of the right coronary artery. Bradycardia and resultatnt hypotension also suggest that there could be ischemic injury to the sinus node as well – the sinus node is normally perfused by the RCA
EKG change –> occlusion?
ST elevations in leads II, III, AVF?
ST elevations in leads V1-V4?
ST elevations in V5 and V6 (maybe I and AvL)
ST elevations in leads II, III, AVF? RCA, transmural ischemia of the inferior wall of the left ventricle (maybe sinus node dysfucntion)
ST elevations in leads V1-V4? proximal LAD, anteroseptal transmural ischemia
ST elevations in V5 and V6 (maybe I and AvL): lCX transmural ischemia of the lateral wall of the left ventricle
What are the compoents of sarcomeres?
A single sarcomere is the distance between 2 Z-lines, it is composed of overlapping filaments of actin and myosin as wel as structural and binding proteins (titin, alpha-actinin)
The thin = actin filaments, in the I band are bound to the structural proteins at the Z-line; unbound ends project into the middle of the sarcomere, where they interact with thick / myosin filaments during muscle contraction
A band always remains the same length during muscle contraction (A for Always)
M line is where the MYOSIN filaments achor structure elements in the center of the sarcomere
Myosin and actin filaments overlap at the segment of the sarcomere between the H and I bands
I band = region of the sarcomere in which actin does not overlap with myosin, only actin
H band = region where myosin does not overlap with actin, only myosin
H&I band shorten during contraction
Resting tremor of Parkinson’s vs inherited essential tremor?
Patients with Parkinson dz have a RESTING tremor vs an essential tremor is classically worsen while maintiang a particular posture ( ie-holding an object = drinking from a glass, pouring tea….)
Essential tremor = most commonly diagnosed movemetn disorder. often follows an autosomal dominant inheritance (positive family history), patients also report that their symptoms subside with alcohol consumption
Tx: propranolol, nonselective B-adrenergic antagonist thought to lessen the tremor via CNS systemic effects
Specificity of a test?
true negatives / total # negatives
Remember specificity –> SPIN, you use it to rule IN a disease
thus, to find the specificity, you want to find out:
(down the 2X2 chart = sensitivity or specificity; across the chart, PPV or NPV)
What is the pathogenesis of prion disease?
What are 2 examples
PrP (prior protein) in normal cellular protein is found in neurons that have alpha-helical secondary structure.
In some patients, this protein undergoes confirmational change from alpha-helical –> b-pleated sheet isoform = highly resistant to proteases, thus causing intracellular accumulation, this accumulation of abnormal protein is thought to cause prion disease
HISTO: affected gray matter –> spongiform change/encephalopathy, vacuoles form within the cytoplasm of neurons and neutrophils; no inflammatory changes*. Later they grow bigger and *form cyst, invoving larger areas of the brain tissue
Examples: Creutzfeldt-Jakob disease, Bovine Spongiform ENcephalopathy (mad cow disease)
