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)
Signs of anaphylaxis reaction
Tx
Pathogen
Sx: skin/mucosal itching, urticaria, angioedema, respiratory distress (laryngeal edema, stridor, hoarseness, bronchospasms, wheezing, chest tightness), GI (NVD), hypotension (dizziness, CV collapse)
TX: intramuscular EPI, airway management and vol resuscitation
Anaphylaxis type 1 hypersen, characterized by increased vascular permeability and multisystem edema, leading to massive shifting of IV fluid to the extravascular compartment. Symptoms often begin within seconds to mintes after intravascular exposure to an inciting factor but can take upt o 2 hours to develop with orally ingested antigens
results in WIDESPREAD MAST CELL AND BA_SOPHIL DEGRANULATION_ and results in HISTAMINE AND TRYPTASE release.
[trypase is an enzyme that is relatively specific to mast cells and elevated serum levels of tryptase are often used to support a clinical dx of anaphylaxis after pt has been stablilized]
where is alk phos found at the highest?
Present in all cells of the body but highest levels found in liver, bone and placenta
How are the mast cells activated in allergic reaction?
High affinity IgE receptor (FceRI) is found on mast cells and basophils and plays a primary role in mediating the allergic response –
The receptor normally binds the Fc portion of circulating IgE (via the sum of many weka non-convalent forces), coating the cell with various antigen specific IgE molecules – when a multivalent antigen comes in contact with teh cell, multiple IgE antibodies become CROSS-LINKED, resulting in AGGREGATION of the FcRI receptors on teh mast cell surface –> clumping of receptors leads to the activation of non-receptor tyrosine kinase, triggering intracellular cascade that ultimate results in mast cell and basphil degranulation
Aortic Regurg:
sound
how is it heard best
high-pitched blowing decrescendo diastolic murmur that beigns immediately after closure of the aortic valve and is best heard along the left sternal border at the third and fourth intercosta spaces while the patient is sitting up and leaning forward with the breath held in end expiratio
What does activation of the insulin receptor mediate and how:
Insulin is an ANABOLIC hormone, that acts via receptor tyrosine kinase signaling to increase the synthesis of glycogen, proteins, fatty acids and nucleic acids.
Insulin binds to the insulin receptor that has intrinsic tyrosine kinase activity @ cytoplasmic domain –> receptor autophosphorylation –> tyrosine phosphorylation of IRS (insulin receptor substrate) –> 2 paths:
1. PI3K path: glycogen, lipid and protein syntheis, also increases GLUT4 vesicle and translocation to the surface
Tyrosine kinase/phosphatidylinositol-3-kinase stimulaiton promotes glycogen synthesis by activating protein phosphatase, an enzyme that dephosphorylates glycogen synthase –> ACTIVATION –> glycogen synthesis
2. Activation of MAP kinase pathway promotes mitogenic functions such as DNA synthesis and cell growth
Insulin decreases blood glucose levels by:
- inc glucose uptake into skeletal and adipose tissue
- promoting the synthesis of glycogen, triglycerides, NA and protiens
- inhibits glycogenolysis and gluconeogenesis
Familial chylomicronemia syndrome:
What is the deficiency
What is elevated
What are the major manifestations?
= type I
What is the deficiency: Lipoprotein lipase, ApoC-2 (apoC2 deficiency activates LPL on chylomicrons and VLDL)
What is elevated: chylomicros
What are the major manifestations: acute pancreatitis, lipemia retinalis, eruptive zanthomas
Familial hypercholesterolemia:
What is the deficiency
What is elevated
What are the major manifestations?
Type II A
What is the deficiency: LDL receptors, ApoB-100
What is elevated: LDL
What are the major manifestations: Premature atherosclerosis, TENDON xanthomas, xanthelasmas
Familia dysbetalipoproteinemia
What is the deficiency
What is elevated
What are the major manifestations?
Type III
What is the deficiency: ApoE
What is elevated: chylomicrons and VLDL remnants
What are the major manifestations: premature atherosclerosis, tuberuptive and plmar xanthomas
Familial hypertriglyceridemia
What is the deficiency
What is elevated
What are the major manifestations?
Type IV
What is the deficiency: polygenic
What is elevated: VLDL
What are the major manifestations: associated with coronary disease, pancreatitis and diabetes
How is greatinine, inulin, PAH, urea and glucose secreted/absorbed/filtered through the kidney?
Creatinine and inulin- freely filtered, an insignificant amount of creatinine is secreted, not absorbed; urinary excretion = filtered load of substance regardless serum concentration
PAH - filtered and activel secreted; even at low serum concentrations, urinary excretion exceeds the total amt filtered
Urea- filtered and rebasorbed via passive diffusion into the peritubular capillaries; 20-50% of the filtered load is normally reabsored but urea has no Tm since it is passively reabsorbed
Glucose- renal tubules reabsorb the entire filtered load of gluc as long as it is below the maximum tubular reabsorption ability (Tm) – at higher plasma concentrations, glucose is excreted when the filtered amt exceeds the Tm of gluc (active reabsorption)
Graves’ dz patient with symptoms of fever and sore throat..what should be the concern?
thionamide-induced agranulocytosis!
Thionamides - MMI, PTU
function by inhibiting thyroid peroxidase impaires iodine organification – MMI is the preferred drug due to the risk of severe hepatotoxicity with PTU
PTU useful for 1st trimester pregnancy, thyroid storm as it has additional effects of decreasing peripheral conversion of T4 to T3
MMI teratogenic
Both PTU and MMI coudl cause agranulocytosis (absolute neutrophil count <500)
sx: fever, sore thora, oral ulcerations + other signs of infections
**if this is suspected, the drug should be discontinued immediately and WBC count with differential should be obtained to confirm diagnosis
Multiple Myeloma
neoplastic B-lymphocytes mature into plasma cells that synthesize abnormal typically large amounts of monoclona immunoglobulin or immunoglobulin fragments (light chains, etc)
* M peak, anemia (normochormic & normocytic), lytic bone lesions (back pain, pathological fractures), renal insufficiency (related amyloid deposition and hypercalcemia)**
SX: impaired hematopoiesis –> normochromic, noormocytic anemia and weakness; lytic bone lesions classically affecting the vertebral column and causign back pain and pathologic features
hypercalcemia and AL amyloidosis (contributes to renal dysfunction)
Severe amyloidosis can also cause cardiac and cutaneous findings
Lab findings: Rouleau formation, bence-Jones (immunoglob light chains) proteins in the urine
serum protein electrophoresis is a more specific laboratory test used to determine if excessive monoclonal IG are present –> an M peak indicates the presence of such immunoglobulins (usually IgG spike)
[an M peak could also be seen in Waldenstrom macroglobulinemia and some other lymphomas]
Most common cause of hirsutism?
= male-pattern hair growth in a women
Most common cause is polycystic ovary syndrome
features: androgen excess, ovarian dysfunction (anovulation), insulin resistance, obesity, many many subcapsular ovarian cyst –> enlarged ovaries
Treatment: wt loss, combined hormonal contraceptives, metformin
OCPs work by suppressing LH secretion from the pituitary thereby decreasing ovarian androgen produciton; also increase sex-hormone binding globulin synthesis by the liver, decreasing free testosterone levels
[pathogenesis: LH –> theca cells –> intra-ovarina androgen –> follicular atresia; hyperandrogemia (hirtusim and other high andregen sx), in the periphery –> E1 –> endometrial hyperplasia/CA and DEC FSH –> cystic deneration of follicles]
virilization occurs w/very high androgen levels – characterized by clitoromegaly, increased muscularity and voice deeping in addition to hirsutism
torticollis?
TX? WHat are other indications for this treatment?
cevical dystonia of the SCM (localized uncontrolled muscle contractions causing pain or discomfort as well as physical deformity)
local injection of botulinum toxin type B into the dystonic SCM muscle results in muscular relaxatio becasue teh toxin prevents presynapic release of ACh (nt responsible for muscle contraction from the nerve terminal at the NMJ)
This effect is temperoary because of nerve terminal eventually regenerates in approx 3 months, thus therapeutic botulinum toxin injections must be repeated when the effects begin to diminish
c. botulinum gram + spore-forming anaerobic bacillus that synthesizes its potent neurotoxins intracellulary and release them by autolysis
**can be used cosmetically to reduce the appearance of glabelar and other facial wrinkles, relax the lower esophageal sphincter in esophageal achlasia, treat muscle spams of MS and PD, and other conditions resulting from involuntary muscle contration**
how can campylobacter infection is acquired?
common cause of inflammatory gastroenteritis
Fecal-orgal transmission- can be acquired from domestic animals (cattle, chicken, dogs!) or from contaminated food
diarrhea is inflammatory and is accompanied by fever, abdominal pain and tenesmus (a continual or recurrent inclination to evacuate the bowels, caused by disorder of the rectum or other illness)
associated with Guillain-Baree syndrome
What is the histopath change in:
Acute neuronal injury (red neuron)
Caused by: transient severe insult that leads to cell death –>
Shrinkage of the cell body, pyknosis of the nucleus (shrunken and basophilic), loss of Nissl substance, eosinophilic cytoplasm
Become visible 12-24 hours after the injury, followed by death of the neuron – remnants are phagocytoized by microglia, astrocytes proliferate on teh site of injury and form a glial scar
reacting to acute irreversible damage = red neuron
*normal aging is associated with progressive atrophy and neuronal loss BUT “red neurons” are NOT characteristic of normal aging
What is the histopath change in:
Axonal reaction (chromatolysis)
cause: loss of axon
–>
enlargement of the cell body, eccentric nucleus, enlargement of the nucleolus, dispersion of the Nissl substance
What is the histopath change in:
Neuronal atrophy
causes: Progressive degenerative disease
–>
Loss of neurons and functional groups of neurons, reactive gliosis
PCA injury - what are the visual defects?
ipsilateral striate cortex, producing a contralateral homonymous hemianopia with macular sparing
you get macular sparing because collateral blood is supplied by the MCA to the occipital pole, which porcesses central visual information
**an MCA stroke is characterized by contralateral motor and sensory deficits (upper > lower limbs) and homonymous hemianopia WITH MACULAR INVOLVEMENT
occlusion of the posterior inferior cerebellar artery?
–> lateral medullary / Wallenbery syndrome
CONTRALATERAL loss of pain and temp sensation
IPSILATERAL deficits in: CN V, VIII, IX, X, XI
Common injury during cardiac catheterization?
The optimal site for obtaining vascular access in the lower extremity during cardiac catherterization is the common femoral artery BELOW the inguinal ligmanet.
Cannulation above the inguinal ligmanet can significantincrease the risk of retroperitoneal hemorrhage
hemoglobin:
adult= HgA: A2B2
fetal: A2G2
alpha always, gamma goes becomes beta
each individual subunit of Hb are structurally analogous to myoglobin so if separated, the monomeric subunits will demonstate a hyperbolic oxygen-dissociation curve similar to that of myoglobin (no cooperativity!)
Note: P50 of Hb is 26 mmHg
P50 of mg is 1 mmHg
–> myoglobin has a much higher affinity for oxygen than hemoglobin
Myoglobin is monomeric and the primary oxygen storing protien in skeletal and cardiac muslce tissue - only found in the bloodstream after muscle injury.
Ankylosing spondylitis
SX:
extra-skeletal system invovlement (3)
Monitoring progression…
SX: low back pain (<40 y/o onset insidious)
morning stiffness that improves with exercise/use
does NOT improve with rest, pain at night
Hip adn buttock pain
limited chest expansion and spinal mobiliyt
enthesitis (inflammation at the site of insertion of a tendon to the bone)
systemic symptoms (fever, chills, fatigue, wt loss)
acute anterior uveitis (unilateral pain, photophobia, blurry vision)
Complications at extraskeletal systems- respiratory (chest expansion should be monitored regularly in pt with AS),
cardiovascular (ascending aortitis –> dilation of the aortic ring and aortic insufficiency/regurg),
eye (uveitis)
RA seronegative! HLA-B27 +
*fusion of sacroiliac joints*
sacroiliac adn apophyseal joints of hte psine are the most commonly affected, leading to restricted spinal mobility
many pt also develop peripheral arthritis adn enthesitis, which is defined as pain, tenderness and swelling at the sites of tendon insertion into the bone (ie- archiilies)
Heparin
MOA
Heparin increases the effect of the naturally occuring anticoagulant antithrombin III (negatively charged chemical stored in mast cell granules)
Binds to AT III via a pentasaccharide in the heparin chain –> conformation change at AT III –> inhibits Xa and neutralizes thrombin –> anticoagulation
Low molecular wt - better availablity, no need for lab monitoring, acts predominatly on factor Xa not thrombin.
Used for: DVT, PE prophylaxis,
Methotrexate
Rescue? does this drug work in another form?
Methotrexate (MTX) is a folic acid analog that inhibits dihydrofolate reductase, enz that converts dietary folic acid to tetrahydrofolate; via direct competition
MTX functions as a chemotherapeutic agent through the inhibition of DNA synthesis and as anti-psoriasis agent through immunodeficiency effects on activated Tcells
BUT causes death of rapidly dividing cells, including those of the GI tract (pt could experience aphthous ulcers) and bone marrow (pancytopenia)
Folinic acid/Leucovorin - can reverse MTX toxicity if given early [reduced form of folic acid that does not need DHFR to be converted to THF, thus it is not affected by MTX]
BUT!! it also potentiates cytotoxicity action of 5-FU (binds thymidylate synthase) and is frequently included in colorectal CA regimens.
Adrenal crisis:
Mgmt-
Sx: HYPOtension/shock, N/V, abdominal pain, weakness, fever
Tx: hydrocortisone or dexamethasone
high-flow IV fluids
Where are parietal cells found in the gastric
Pernicious anemia could suggest an autoimmune disorder of parietal cells of the gastric body and funduns –> chronic atrophic gastritis, wich is characterized by a histolgically loss of parietal cells with marked lymphocytic and plasma cell infiltration.
Parietal cells are oxynitic (pale pink), found an dplate0like cells found predominately in the upper grandular layer that secrete gastric acid and iF
IF is required for the absorption of cobalamin/vit B12 in the ileum, problem with parietal cells –> vit b12/cobalamin deficiency
progressive fatigue, lower-extremity parethesias, megaloblastic RBC = pernicious anemia
Monozygotic vs dizygotic twins?
Dizygotic twins = fertilization of 2 oocytes by 2 different sperm = always 2 amnions and 2 chorions!
Monzygotic twins arise from the fertilization of a single oocyte; twining may occur at different stages which affects the organization of the fetal membranes
0-4 days: Dichrionic/diamnionic
4-8 days: monochro/diamniotic
8- 12 days: monochro/monoam
>13 days = conjoined twins, monochro/monoamniotic
when does the mucociliary clearance end?
terminal bronchioles
After thsi point, respiratory zone. Cilia terminate at respiratory bronchioles. Alveolar macrophages clear debris and partcipate in immne response
Atrial natriuretic peptide (ANP)
Secreted by atrial cardiomyocytes in response to atrial stretch, which is indicative of systemic volume expansion –> lowers BP through peripheral vasodilation, natriuresis and diuresis
ANP binds to the natriuretic peptide R on cell membranes, activating guanylate cyclase and forming cGMP
Organs and tissues affected: kidney, adrenal gland blood vessels
[overall vasodilation, increase sodium excretion/decrease reabsorpiton]
what would failure of a pt neutrophils to turn blue on nitroblue tetrazolium testing indicate?
characteristic of chronic granulomatous disease - condition most often caused by an X-linked mutaiton affecting NADPH oxidase
nl actiaved phagocytes to produce reactive oxygen species taht act directly as antimicrobial agents and activate granule proteases present in phagosomes
Inactivating mutations of NADPH oxidase cause impaired intraceular killing by neutrophils and macrophages, leading ot recurrent bacterial and fungal infections…especially caused by CATALASE POSITIVE organisms (can destroy the hydrogen peroxide produced by their own metabolic activity)
what is the importance of coagulase produced by some bacteria?
S. Aureus contains coagulase
activates prothrombin, resulting in conversion of fibrinogen to fibrin –> fibrin-coating of the organism and resistance to phagocytosis
What bacteria’s toxin is lecithinase?
Lecthinase is also known as alpha toxin – this is an enzyme with phospholipase C activity and the major virulence factor produced by C. perfringens
Toxin increases platelelt aggregation and adherence molecule expression on leukocytes and endothelial cells, resulting in vasooclusion an dishcemic necrosis of affected tissues
Reid index?
The reid index is the ratio of the thickness of the mucous gland layer in the bronchial wall submucosa to the thickness of the bronchial wall btwn the respiratory epithelium and cartilage (not including the cartilage)
It is snensitive measure of mucous gland enlargement - since progressive mucos gland enlargement is the major contributor to gradula bronchial wall thickening in chornic bronchitis, and since increasing wall thickness causes worsening airflow obstruction, elevaiton of the reid indez above the normal value of 40% correlate well with the duration and severity of chronic bronchitis
How can primary herpes simple virus present in children?
infection in children causes gingiovostomatitis = vesicular lesions on the lips and hard palate.
HSV1 and other herpes virus are double stranded, enveloped DNA viruses
*Coxsackievirus causes hand, foot, mouth disease but spare the hardpalate and gums. (usually seen in the buccal mucosa, tongue and soft palate)
what drug intoxication could we see nystagmus?
PCP = phencyclidine
hallucinogen that causes dissociative symptoms, agitation, hallucinations and violent behavior
Ataxia, nystagmus and memory loss are other distinguishing sx of PCP abuse
three most important predisposing factors for hypoglycemia in pt with type I DM?
excessive insuline
inadequate food intake
physical activity/exercise
[glut 4 translocated to the cell membrane in response to insulin and muscle contraction!]
[infection, pain and sleep deprivation tend to cause HYPERglycemia rather than hypoglycemia- stressful situations increases catecholamine release, which rasies glucose by decreasing pancreatic insulin secretion and by increasing glycogenloysis and gluconeogenesis]
Tricylcic antidepressant overdose presentation:
mental status changes, seizures, PROLONGED QRS duration, ventricular arrhythmias and anti-cholinergic findings
cardiac symptoms are caused by blockage of cardiac fast sodium channels and inhibition of muscarinic acetylcholine, histamine and alpha-1 adrenergic R
Sodium bicarnonate is used to treat associated cardiac toxicity and works by increasing serum pH (favoring the non-ionized/neutral form of the drug, thus less accessible to binding sodium channels) and increasing the extracellular concentration of sodium, which helps overcome the competitive inhibition.
which parts of the TCA cycle are dependent on thiamine?
Pyruvate –> acetyl coA
alpha-ketoglutarate –> succinyl-coA
What is a releasing factor 1?
Releasing factor proteins bind to the ribosome when a ribosome encodes a stop codon (UGA, UAG, UAA) –> stimulate release of the formed polypeptide chain and dissolution of the ribosome-mRNA complex
What is CA-125 indicative of?
Additional risk factors and protective factors?
Cancer antigen 125 is aprotein produced by ovarian epithelia and is usually markedly elevated in cancerous ovarian cells compared to normal cells.
It is neither sensitive nor specific for early EOC as it can be found in normal tissue and other cancers
Risk factors for EOC: BRCA1/2 mutations, lynch syndrome repeated ovulation (nulliparity), ovarian dysfunction, endometriosis, postmeno age
Protective factors: oral contraceptives, multiparity, breastfeeding, tubal ligation, salpingo-oophorectomy
During a car accident, what damage could it cause to the heart?
what area of the heart is most likely to be damaged?
Blurt aortic injury is most commonly caused by MCV
underying mechanism is due to a sudden deceleration that results in extreme stretching and torsional forces affecting the heart and the aorta
The most common area to be injured is teh aortic isthmus, which is tethered by the ligamentum arteriosum and is relatively fixed and inmonile compared to the adjacent descending aorta
most pt die from aortic rupture before reaching hospital; otherwise have unspecific symptoms such as chest pain, backpain, SOB..widen mediastinum could be seen on x-ray
isthmus > ascending aorta > descending aorta
What is the path of the duodenum?
First part emerges from the pylorus and is horizontal over the first lumbar - only part of the duodenum that is not retroperitoneal
second part courses inferiorly at L1-L3; relatively close to the head of the pancreas and contains ampulla of Vater, site where pancreatic and common bile duct secretions are released
Third part of the duodenum courses horizontally over L3, the abdominal aorta and inferior vena cava; it is in close association with the uncinate process of the pancreas* and the *SMA
Fourth part of the duodenum courses superiorly and to the left of L2 and l3 –> becomes jejunum past the ligament of treitz
Function of glucagon?
glucose increases serum glucose by increasing HEPATIC glucose production via GLYCOGENOLYSIS and GLUCONEOGENESIS.
Glucogon-induced glycogenlysis is the predominant initial means of rapidly increasing blood glucose levels during hypoglycemia.
Functions by stimulating G protein-couple dreceptors –> increasing cAMP –> activating protein kinase A
–> activation of glycogen phosphorylase = key glycogenolytic enzyme
Activates rate limiting gluconeogenetic enzymes (pyruvate carboxylase, phosphoenolypyruvate carboxykinase)
DEC intracellular fructose 2,6, bisphosphate (inhibiting glycolysis)
**during the first 12 hours of fasting, hepatic glycogenolysis is the source of most of the body’s glucose
Glucago has an insignificant effect on glucose homeostasis in skeletal muscle, adipose tissue and renal cortex
DSM-5 diagnositic criteria for Narcolepsy:
Reccurent lapses into sleep or naps (min 3X per week for 3 months)
At least 1 of the following:
Cataplexy- brief loss of musc tone precipitated by strong emotion (laughter, excitment..)
*Low CSF levels of hypocretin-1
*Shortened REM sleep latency, enter REM almost immediately
Associated features: hypnagogic or hynopompic hallucinations, sleep paralysis
Narcolepsy results from the depletion of hypocretin-secreting neurons in the lateral hypothalamus that involved in maintaining wakefulness
Treatment options for C. diff infection:
oral metro (mild to moderate cases)
Vancomycin (severe cases)
Fidaxomicin (macrocyclic antibiotic that inhibits teh signma subunit of RNA polymerase, leading to protein syntehsis impairment and cell death; oral, bacteriocidal activity, minimal systemic absorption, narrow spectrum; less effect on normal colonic flora than either metro or vanco - for patients with recurrent C diff or at an increased risk for recurrence.
Hyperacusis?
Increased sensistivity to everyday sounds
One of the causes could be due to injury or lesion to the facial nerve. The stapedius nerve is a branch of the facial nerve, and innervates the stapedius muscle. This muscle serves to stabilize teh stapes. paralysis of the muscle, causes the stapes to oscillate mroe widely, producing hyperacusis
ipsilateral hyperacusis is a common finding of Bell’s palsy
tx: re-training/sound therapy suing broadband noise/white noise
Hemochromatosis triad:
“bronze diabetes”
skin hyperpigmentation, diabetes mellitus, pigment cirrhosis with hepatomegaly
Hemochromatosis is an AR disease characterized by abnormally high iron GI absorption –> iron overload, primarily in parenchymal organs such as the heart, pancreas and liver
Lbas: mildly elevated LFT, elevated plasma iron with more than 50% saturation of transferrin and elevated serum ferritin
what are the different dopamine agonist available?
DIRECT agonist of dopamine –directly stimulate R
Ergot compounds: bromocriptine
nonergot: pramipexole and ropinirole
Others:
selegiline inhibits MOA-B, resulting in decrease central dopamine degradation
Amantadine - enhances effects of endogenous dopamine
COMT inhibitors (entacapone, tolcapone) and dopa decarboxylase inhibitors (carbidopa), decrease breakdown of levodopa in peripheral tissue,and increase amt of levodopa available to cross teh BBB
Easy fatigability, constipation, back pain, eevated serum protein, azotemia in an elderly person should raise teh suspicion for?
Multiple Myeloma
Large eosinophilic casts composed of bence-Jones proteins are seen in the tubular lumen in myeloma cast nephropathy
physical presentation of necrotizing entercolitis in an infant:
pneumatosis intestinalis (air in the bowel - seen on abdominal x-ray as think curvilinear areas of lucency, parallel the lumen), abdominal distension, bloody stools
one of themost frequent GI emergencies affecting newborns,
RF: preterm infants due to GI an dimmunologic immaturity; thus upon enteral feeding, bacteria are introduced into the bowel wehre they proliferate excessively due to compromised immune clearance - impaired mucosal barrier allow the bacteria to invade the bowel wall, causing inflammation adn ischemic necrosis of the terminal ileum and colon –> bowel becomes congested and grangrenous with formation of intramural gas collections
30% fatality
surivivors are at risk for: strictures, bowel obstruction secondary to fibrosis
glucose-6-phosphate dehydrogenase (G6PD) deficiency:
x-linked disorder
> pt of african, asian and mediterranean descent
enz impt for pentose phosphate pathway
impt in RBC for maintaining adequate concetrations of NADPH
Deficiency –> low NADPH, difficulty maintaining glutathione in teh reduced state –> increase vulnerability of RBC to go into oxidative stress –> hemolysis induced by infection, drugs (bactrim, dapsone, anti-malarials, nitrofurantoin) and other oxidants (fava beans)
Aldose B deficiency?
Hereditary fructose intolerance (AR)
Inability for fructose 1-phosphate –> DHAP and glyceraldehyde (enters glycolytic pathway)
sx: hypoglycemia and vomiting after frutose ingestion, failure to thrive, liver and renal failure
tx: strict abstinence from dietary fructose ans sucrose (fructose + glucose) from diet
This deficiency leads to the accumulation of the toxic metabolite fructose-1-phosphase.
–> deplets intraceullar phosphate, inhibits activation of hepatic phosphorylase and gluconeogenesis –> lifethreatening hypoglycemia (sx: lethargy, sweating, vomiting, dehydration)
Labs of liver function?
indicators of livery injury?
For liver function:
Impaired biosynthetic capacity?
Elevated PT
hypoalbuminemia
Impaired transport and metabolic capacity?
elevated bilirubin
For liver injury:
Markers of hepatocyte injury
Aaspartate aminotransfere, alanine aminotransferase
AST > ALT usually
Makers of cholestasis:
- elevated alk phosphase, elevated gamma-glutamyl transpeptidase (ggt not elevated in bone dysfxn)*
other: thrombocytopenia (due to splenic sequestration of platelets)
_** best markers for cirrhosis function: albumin, bilirubin, prothrombin time**_
Origin and function of pudendal nerve:
origin: S2-S4
Sensory: perineum
Motor: urethral and anal sphincters
important landmark for PN block:
ischial spines [bony protrusions loc posterior lateral to vaginal side wall]
sacrospinous ligament [firm band that runs medially and posteriorly from teh ischial spine to the sacrum]
*when administering a PN block, the ischial spines should be palpated intravaginally and the anesthetic should be injected medially in very close proximit to the ischial spine through the sacrospinous ligament
*internal pudendal artery and inferior gluteal artery, run medial to the PN; inadvertent injection can lead to hematoma and arrhythmia from intravascular infiltration of local anesthetics
origin and function of genitofemoral:
L1-L2
sensory to scrotum/labia majora
medial thigh (obturator does too)
Tracheoesophageal fistula with esophageal atresia?
results from failure of the primitive foregut to appropriately divide into separate trachea and esophageal structures
Infants present shortly after birth with excessive secretions and choking/cyanosis during feeding
dx: x-ray after the inability to pass a nasogastric tube into the stomach; could also show a stomach bubble, which results from air flow from the trachea through the fistula to the distal esophagus
where should a thoracentesis be performed?
above the 8th rib in the midclavicular line, 10th rib along the midaxillary line and 12th rib along the posterior scapular / paravertebral line
Insertion of the needle lower than these points increases the risk of penetrating abdominal structures and insertion of hte needle on the inferior margin of the rib risks stricking subcostal neurovascular bundle (VAN)
Monoamine oxidase (MAO) enzyme effects what neurotransmitters?
What do pt taking this drug need to be careful with?
MOA is a mitochondrial enzyme that:
degrades excess monoamine neurotransmitters in presynaptic nerve terminals
detoxifies dietary tyramine in the GI tract
Tyramine hypertensive crisis can occur in pt taking MAO inhibitors following consumption of foods containing high amounts of tyramine (aged cheeses, cured meats, draft beer)
–> hypertensive emergency (severe HTN, h/a, blurry vision)
excessive sympathetic activity (tachycardia, diaphoresis, tremors)
*tyramine is an indirect sympathomimetic that is usualy metbaolized in the GI tract by MAO
Homocystinuria
Most common deficiency
clinical presentaiton
Homcystinuria:
most commonly affected enzyme = cystathionine synthase –> affected pt can’t form cystein from homocystein –> cysteine becoming essential
Homocystein builds up –> hypermethioninemia
Homocystinuria is a condition that leads to hypercoagulability and thromboembolic occlusion; pt with complete cystationine synthase deficiency can develop premature acute coronary syndrome, ectopia lentis (ocular lens displacement) and intellectual disability
others also needed: serine, cofactor B6, cystathionase
what stain is used to dye fat in certain situations?
osmium tetroxide, imparts a black color to fat
Iron stains
For example ferruginous bodies, (accumulation of iron in the lung by coating asbestos fibers –> ferruginous bodies)
stain brown on H&E
dark blu eon Prussian blue stain
What would a viral meningitis CSF look like?
Glucose - normal
protein - INCREASED
cells - 90% LYMPOCHYTES
CSF for bacterial meningitis?
glucose - LOW
Protein - HIGH
cells - Neutrophilia
How is multi-compartment drug metabolism established?
Liphophilic drugs (such as propofol) can be predicted using multi-compartment model of distribution
administration of a single bolus:
drug levels are high in the central comparments (plasma)
then quickly distributed to well-vascularized peripheral compartments (brain, liver, kidney, lungs) due to increased lipohilicity of the tissues compared to the blood
then over time, it is redistributed into poorly vascularized peripheral comparments (skeletal muscle, fat, bone) which has the highest volume of distribution for lipohilic agents
** redistribution occurs rapidly with highly lipohilic drugs and is responsible for the short duration of action seen with commonly used anesthetics such as propofol
Pathogenesis of supraantigens
Interact wtih major histocompatibility complex molcules on antigen presenting cells and the variable region of the T lymphocyte receptor to cause nonspecific, widespread activation of T cells.
This results in release of IL2 from T cells and IL1 and tumor necrosis factor from macrophages.
The immune cascade is responsible for the manifestations of toxic shock syndrome
S. Aureus #1 culprit
IL activation causes capillary leakage, circulatory collapse, hypotension, shock, fever, skin findings, multiorgan failure
What is the heart malformation seen in Turners syndrome?
Bicuspid aortic valve is the most common congenital cardiac malformation in pt with TS
Usually isolated but could occur with other abnormalities such as aortic coarctation
nonstenotic bicuspid aortic valve manifests wtih aortic ejection sound, which is an early systolic, high frequency click heard over the right second intersapce – as it calcified, progressive valvular dysnfunction with aortic stenosis or regur will be produced.
susceptible to infectious endocarditis
Churg-Strauss / Eosinophilic Granulomatosis with polyangiitis
small to medium vessel vasculitis, characterized by late-onset of asthma, rhinosinusitis, eosinophilia (could invovle kidneys, GI, VC)
*peripheral eosinophilia, antibodies against neutrophil myeloperoxidase pANCA
*asymmetric multifocal neuropathy/ mononeuritis multiplex) common due to vasculitis affecting the epineural vessles
- skin nodules
- migratory/transiet pulmonary infiltrates
- paranasal sinus abnormalities
Pulmonary artery catheters (PACs) =
Swan-Ganz or right heart catheters are used to diagnose PULMONARY HTN, occasionally for management of critically ill patients
measures pulmonary artery occlusion pressure or pulmonary capillary wedge pressure, closely reflects left atrial and left ventricular end-diastolic pressures
during pulmonary artery catherization, ballow of the distal tip of teh catheter is inflated and the catheter is advanced forward through the right atrium, right ventricle and pulmonary artery and into a branch of the pulmonary artery..once lodged, the ballow is inflated obstructs blood flow, creating a continuous static column of blood bwt the cateter tip and left atrium
Goodpasture syndrome-
name IF, light microscopy and physical findings
caused by anti-GMB antibodies that react with a component of the alpha3-chain of collagen type IV. Patients typically present with rapidly progressive glomerulonephritis resulting in acute renal failure and hemoptysis due to pulmonary hemorage (anti-GBM antibodies cross react with other BM, especially those in the lung alvoli)
LM: crescent formation with fibrin deposition
FM: linear IgG and C3 deposition
Nephritic = RBC casts, mild proteinuria
type II hypersensitivity
tx: emergent plasmapheresis
Why are keloids formed?
Wound contraction, a nl part of proliferative phase of would healing, involved contraction of actin in myofibroblast to approx wound edges. Transformation growth factor-beta (TGF-b) promotes differentiation of fibroblast into myofibroblast adn should diminish on completion of wound repair.
In Keloids, TGF-b is produced excessively withouth regulation –> scar extends beyond the borders of the original would, do not regress adn often recur after resection
(collage 3)
arise following minor or major trauma, can be raised, painful and pruritic
familial tendency, particularly in persons of asian or african ethnicity
side effect of acyclovir
what could be done to preven this from occuring
Acyclovir can cause crystalline nephropathy if adequate hydration is not also provided!
Could be seen with acute elevations of serum creatininte –> nephrotoxicity
5-10% of patients who receive drug via IV
drug excreted primarily via glomerular filtration and tubular secretion, thus when concentration in collecting duct exceeds its solubility, crstallization, crstalluria dn renal tubular damage may result
What are some forms of resistance against aminoglycosides?
AG bind to the 30s ribosomal subunit –> causes cell to misread mRNA and as a result unable to perform protein synthesis
Important forms of resistance:
- methylation of the AG binding portion of the ribosome, inhibiting the ability of AG to interfere with protein translation
- production of enzs that inactivate teh drug by altering its chemical structure
- efflux pump that dec teh drug’s intracell conc
treatment for HER2 positive breast cancer?
Adjuvant therapy with monoclonal antibody against tyrosine kinase receptor =Trastuzumab
human epidermal growth factor receptor 2 (HER2)
trastuzumab binds a portion of the extracellular domain of HER2 and prevents activation of the transmembrane tyrosine kinase –> this downregulates cellular proliferation and promotes apoptosis
hER2 tyrosine kinase receptor is overexpressed in 20% of breast cancer patients
What is a non-preventable adverse effect? what is a preventable adverse event?
what is a sentinel event?
A preventable AE = injury to a patient (ie -delayed dx) due to failure to follow evidence-based best practice guidelines
Non-preventable error is a complication that cannot be prevented given the current sate of medical knowledge (ie - allergic rxn)
Sentinel event = unexpected occurrence involving death or serious physical or psychological injury (inpatien suicide, death of a full-term infant, retained object after surgery) that required immediate investigation
What effect does simvastatin and cholestyramine have on hepatic cholesterol?
Statin: decrease
cholestyramine: increase
Statins are first line for most pt with hypercholesterolemia; competitively inhibit HMG CoA Reductase - enzyme responsible for the conversion of HMG CoA to mevalonate – DECREASING hepatic cholesterol synthesis, instead upregulating LDL receptors causes an increase in LDL from the circulation
(statin effect on TG and HDL are comparatively modest)
Bile acid-binding resins (bile acid sequestrants such as cholestyramine) act by binding bile acids in the GI tract, interfering with the enterohepatic circulation of bile acids adn causing INC bile acid excretion –> hepatic synthesis of NEW bile acids, thus consuming liver choelsterol stores, and hepatic uptake of LDL from the circulation for continued bile acid synthesis. hepatic choelsterol reduction is an actiating factor for HMG CoA reductase adn subseuently results in INC hepatic choelsterol synthesis
This effect can be blocked with the addition of a statin drug to the treatment regime –> greater reduction in LDL = synergistic action
When can bacteremia with viridans strep cause a problem?
With injury to the cardiac valves!
Viradans is a gram positive organism taht is able to produce extracellular polysac = dextrans using surcose as a sbstrate – dextrans faciliate strep adherence to FIBRIN
Fibrin adn plateles are depsoited at sites of endothelial trauma, providing a site for bacterial adherence and colonization during bacteremia
In pt with pre-existing valvular lesions, viridans can adhere to teh affeted valve and est infection –> endocarditis
* the risk of endocarditis following dental procedusre is low with MVP, and antibiotic prophylaxis is not recommended although cases can still occur
tx of acute gouty arthritis vs chronic gout:
Acute gouty arthritis, treat with NSAIDS (contraindicated in pt with renal failure or PUD) as first line, or colchicine as second line therapy, glucocorticoids
For chornic gout - allopurinol (inhibits xanthine oxidase, which converts xanthine to uric acid) or probenecid (decreases proximal tubular uric acid reabsorption)
*contraindicated in acute gouty arthritis*
what histology could be seen with MS pt?
The hallmakr of MS is demyelination of the axons, which can occur in any area of white matter
Loss of myelin sheaths and depletion of oligodendrocytes is seen within the plaques
Lipid laden macrophages containing the products of myelin breakdown are also seen within plaques
Astrocyte proliferation response to CNS injury
MRI brain scan is dx, typically showing demyelinating plaues
CSF demonstarte INC conc of IgG – oligoclonal band on protein electrophoresis
conduction velocity slows in MS due to demyelination
Blast cells in the peripheral blood are strongly suggestive of leukemia.
ALL is the most common pediatric malignancy - the neoplastic cells of ALL arise from lymphocytic precursors that are either pre-B or pre-T
how could we tell the difference?
ALL sx: fever, fatigue, pallor, petechiae, bleeding.
Leukemia coudl spread causign lymphadenopathy, hepatosplenomegaly and bone pain
T-ALL is more likely to present with anterior mediastinal mass that can compress teh great vessels –> superior vena cava syndrome; respiratory symptoms, dysphagia. only about 15-17% of cases
B-ALL manfiests with fever malaise bleeding bone pain hepatosplenomegaly but not really with mediastinal compression
most common!
Both will contain TdT (an antigen of lumphocyte precursor)
pre-B cell surface markers: CD 10+, 19+, 20+
pre-T lymphoblast: CD2+, 3+, 4+,5+,7+,8+
What is the prognosis of colorectal adenocarcinoma related to?
STAGE not grade!!
Extent of tumor expansion = stage
vs degree of tumor differentiation = grade
Stage A - confied to the mucosa, 90% survival + 5 yr
if it involved the muscular layer = stage B 70-80% 5y
C = lymph node involvement
d= distatn mets, poor prognosis
Rett syndrome
Characterized by loss of speech and motor skills, deceleration of head growth, steretypic hand movements aft_er a period of normal development (5-18months) –> loss of motor and language skills and development of stereotypic hand movements_
neurodevelopment disorder that affects mainly girls
associated with mutations in the MECP2 gene
when is the greatest and least blood flow in the myocardium?
During ventricular systole, the myocardial blood vessels are compressed by the surroudining muscle –> majority of LEFT ventricular blood flow occurs during DIASTOLE
the systolic reduction in coronary blood flow is greates in teh SUBENDOCARDIAL region, making thsi portion of the left ventricle most prone to ischemia and infarciton.
What is the pressures surroudning the lung volumes at functional residual capacity
The center of the airway pressure-volume curve is the functional residual capacity of the lungs.
Identifies teh resting state where the airway pressure equals zero.
at FRC, the intrapleural pressure is negative with a value of -5 cm H20
During inspiration, the intrapleural pressure decreases to ~ -7.5 cm H20, which hten induces a slightly negative alveolar pressure that drwas air into the lungs.
(atmos pressure - 0) –> pneumothorax causes the lung to collapse and the chest wall to expand out
due to elasticity of the lungs, the alveolar transmural pressure is always positive, resulting in a perpetual collapsing force on teh lungs –
what is the single most preventable cause of death
Tobacco use, esp smoking is the single most preventable cause of death and disease in the US
- direct adverse effects
- increases risk for macrovascular (MI, stroke)
**the risk of MI associated mortality begins to decrease immediately upon smoking cessation**
- inc risk for microvascular (DM)
smoking cessation has a greater effect on reducing mortality than a daily aspirin, dietary and exercise modifications
What is the genetics behind achondroplasia?
Occurs as a sporadic mutation due to advanced paternal age in 85% of the cases as an inhereted AD in the 15% remaining
homo dominant individuals usually are fatal, thus any affected individual is probably heterozygous thus 50% chance of passing on the gene
results in a GAIN OF FUNCTION mutation in the FGFR3 gene
Achonrdoplasia is the most common form of short-limbed dwarfism and is caused by a mutation that results in constitutive activation of fibroblast growth factor receptor 3.
Hep E
unenveloped, single stranded RNA virus spread through fecal-oral route
**high mortality rate in infected pregnant women**
INC incidence- young, middle-aged adults living in asia, sub-saharan africa and mexico with an average incubation period of six weeks.
typically self limited, no chronic liver disease or carrier state
anti-Rh(D) immunoglobulin class
IgG
Anti-Rh immune globulin consists of IgG anti-D antibodies that opsonize Rh+ fetal erythrocytes, promoting clearance by maternal reticuloendothelial acrophages and preventing maternal Rh sensitization. It is routinely administered to Rh negative women at 28 weeks gestation and immediately postpartum.
Rh antigens are a group of non-glycosulated, transmembrane proteins on the surface of RBC
D antigen is the most immunogenic of the group
present on RNC of Rh-positive individuals
When an Rhnegative mother becomes pregnant with an Rh positive fetus, fetal RBC can enter the maternal circulation and elicit a maternal IgG antibody respone with formation of memory B-lymphocytes (Rh allimmmunizaiton)
After Rh alloimmunization occurs, subsequent pregnancies with Rh-positive fetuses will be at risk for hemolytic disease of the newborn
To prevent maternal Rh allominnunization, Rh-negative motehrs must be prevents form mounting an immune response agaisnt D antige –> anti-RhD immunge globulin is a polyclonal antibody consisting of IgG anti-D antibodies collected from pooled donor plasma –> antiRhD antibodies bind to Rh-positive fetal RBC that enter the maternal circulation, preventing the interaction with the maternal immune system via sequestration and elimination by the mother’s spleen
administration of anti-D IgG during preg does not cause significant transplacental fetal hemolysis because the quantity of anti-RhD administration is very small compared to that produced in a typical immunologic reation
alkaptonuria:
AR disorder in which the lack of homogentisic acid dioxygenase blocks the metabolism of tyrosine leading to the accumulation of homogentisic acid
clinical features include a black urine color when exposed to air; selectively binds to collage in connective tissues, tendonds and cartilage – a blue-black pigment on the face and ochronotic arthropathy
when would it be most likely for us to see a zinc-finger receptor?
zinc-finger motifs are composed of chains of AA bound together around a zinc atom via linkages with cystein and histidien residues
they recognize specific DNA sequences and are used by many transcription factors to bind DNA and alter activity of target genes.
only INTRAacellular receptors that bind steroids, thyroid hormone and fat-soluble vitams act diretly as transcription factors and contain zinc-finger binding domains (others can act indirectly, via signal transduction cascades involving second messangers)
zinc-finger is the most commonly identified DNA-binding domain in humans
Diabetes during pregnancy:
associated with a number of neonatal complications including transiet HYPOglycemia
in preg women with poorly controleld DM, fetus is subjected to high blood gluc levels since glucose can freely cross BUT maternal insulin does not cross –>fetabl hyperglycemia leads to a compensastory rise in fetal insulin produciton and iselt cell hyperplasia
fetal hyperinsulinemia –> abnormal fetal growth resulting in macrosomia
After birth, since the neonate is not longer exposed to high glucose levels of the mother but a hyperinsulinemic state persists for several days –> hypoglycemia
usually resolved in 3-7 days
where can we find the most deoxygenated blood in the body?
Coronary venus sinus
most drains directly into teh right atrium with the remainder raining into the other chambers of the heart
Importance differences btw heart and other skeletal muscle and viscera blood flow:
- myocardium is perfused during diastole (myocardial contraction during systole leads to compresison of the coronary arteirs and disruption of blood flow - contraction force is highest near the endocardium, resulting in severe coronary vessel compression in this area –> subendocardium is most prone to ischemi)
- myocardial oxygen extraction is very high
- myocardia oxygen demand and coronary blood flow are tightly boupled - (adenosine and NO are the most important vasodilators responsibelf or increasing coronary flow)
What are drugs associated with an increase risk for falls?
psychotropic drugs - antipsychotics, antidepressants, benzos are the class most commonly associated with increased fall risk
TCAamitrityline and long acting diazepam
calcium channel blockers - amlodipine
ibuprofen NSAIDs
MCL
MCL attaches proximally to the meidal epicondyle of hte femur and resists foces that push the knee medially
MCL injury typically occurs after a twising injury or blwo to the lateral know while the foot is planted (valgus stress inury)
valgus stress test is positive indicating a MCL injury when tehre is laxity of hte know and/or medial joint line widening indicating MCL injry
PTH
Receptors predominantely on bone and kidney tubules
timulates teh formation of cAMP via Gprotein/Adenylyl cyclase pathwya
on bone –> resorption; PTH receptors located on osteoblast no clasts! —> causes osteoplast to increase RANK L and moncocyte CSF —> these two factors stimulate osteoclastic precursors to differentiate into bone-resorbing, mature osteoclasts
DEC release of OPG – “decoy” of recetor for RANK ligand.
INC serum calcium (both resportion and from reabsorption oin the kindey) and decrease teh absorption of phosphorus from kidney tubules
increases the activty of a-alpha hydroxylase increasing vitamin D in the kidneys
Vitamin D does cause hypercalcemia but will not cause phosphaturia because PTH secretion diminished when there are high levels of calicum in the blood– less active in discouraging phosphorous resprtption in the kindeys
why do pt with liver cirrhosis have increased estrogen?
What does this manifest as
IN cirrhotic pt, gynecomastia arised from hyperestrinims due to increased adrenal production of androstenedion with aromatization to estrone and eventual conversion to estradiol
estradiol induces sex hormone binding globulin production (primarily in the liver but also in the uterus and testes), which results in increase T binding and decreased free T/E raio
other manifestaiton of hyperestrinims in cirrhotic pt include spider angiomata, and in males testicular atrophy and dec body hair
spider angiomata blanch on compression
and size generally correlate with severity of liver disease
PYR test..what bacteria is postive?
pyrrolidonyl arylamidase test
S. pyogenes is positive
** glomerulonephritis is associated with prior strep pharyngeal or skin infection
Acute rheumatic fever is associted with prior strep pharyngitis but NOT SKIN infection
What is the most common intra-abdominal organ injured during blunt trauma?
The spleen (mesodermal with arterial suplly by a foregut vessel -itself is not a foregut derivative)
iti s an intraperitoneal (not retro!)
derived from mesoderm of the doral mesentary
spleen is unique in that its bloody supply derives from a foregut derivative (splenic artery of the celiac trunk). venous retunr from teh spleen course through teh splenic vein to return to the portal circulation rather than the systemic circulation
PICA
compulsive consumption of nonfood and/or non-staple food source for greater than 1 month
most common in: pregnant women and school children
ingested substance is not a culturally accepted food source and the consumption is not appropriate to the person’s development level
often but now always associated with nutritional deficiencies, including iron and zinc deficiencies and anemial of any etiology
three main types of subsances consumed: earth/soil rich substances, raw starch such as forn or corstach and ice
What is the major protease of extracellular elastin degradation?
Neutrophil elastase
it is released by neutrophils and macrophages
major serum inhibitor ofe xtraceullar elastase is anti-1-antitrypsin (AAT)
AAT deficiency could lead to panacinar emphysema and liver cirrhosis; panacinar emphysema results from teh unoppose action of neutotphil elastase on alvolar walls and smoking dramatically icnreases the risk of panacinar emphysema in pt with AAT def by inducing inflammaiton (increasing neutrophil and macrophage activation) and permanently inactivnat AAT through oxidation of a crucial methionine residue
Heliotrope rash, gottron’s papules and proximal muscle weakness should hit to…
dermatomyositis…systemic AI dx like polymyositis with additional inflammatory features involving the skin
Muscle biopsy is dx and shows mononuclear perimysial infiltrates, perifascicular atrophy and patchy necrosis with CD4+ T cells
**consider underlying malignancy / increased risk for occult malignancies - colorectal, lung, ovarian, non-hodgkins lymphoma
What is the D-xylose test used for?
D-xylose is absorbed at the proximal small bowel via passive diffusion and is used to differentiate pancreatic from intestinal malabsorption.
how can you test for lactose intolerance?
lactase deficiency results in incomple hydrolysis of the disac lactose into monosac gluc and galatose –> osmotic diarrhea
bacterial fermentation of lactose produces short-chain FA acids which lowers stool pH <6, hydrogen gas which causes flatulence
undigested lactose causes an elevation in stool osmotic gap (>125) indicating the presence of unmeasured anions in the stool
Bacteroides:
gram negative anaerobic rods that can produce B-lactamase
tx: piperacillin-tazobactam (combo of extended-spectrum penicillin with B-lactamase inhibitor)
effective against most gram negative enteric rods (including pseudomonas aerugionsa) and bacteroides frailis
areas of necrosis and diminished blood suppply (such as chronic and nonhealing ulcers) faciliate the growth of anaerobes
myophosphorylase deficiency?
McArdle disease or glycogen storage disease V = glycogen phosphorylase deficiency
causes failure of muscle glycogenolysis resulting in decreased exercise tolerance, muscle pain and cramping, myoglobinuria with physical activity
Nonnucleoside reverse transcriptase inhibitors?
NNRTis are antiretrovirals that do not req. activation via intraceullar phosphorylation
THe more common NNRTis include nevirapine and efavirenz
best used in conjucntion with other antiretroviral agents for the tx of HIV
AEs: abrupt-onset flu-like symptoms, abdominal pain, jaudice or fever may indicate potentially life-threatening hepatic failure (most likely during the first 6 weeks of NNRTi therapy)
Life threatening skin reactions SJS, TEN have also been observed
inhibit the syntehsis of viral DNA from teh RNA template
Thrombotic thrombocytopenic purpura:
DEC ADAMTS13 –> large vWF multimers and resulting in diffuse microvascular platelet-rich thrombi
or acquired/autoantibody
or hereditary
clinical prese: hemolytic anemia (INC LDH, DEC haptoglbulin) with schistocytes
Thrombocytopenia (INC bleeding time, nl PT/PTT)
sometimes - renal failure, neurologic manifestations, fever
Mgmt: plasma exchange
What are MAOs
Tranylcypromine
phenelzine
selegiline
MAO is an enzyme located in presynaptic nerve terminals that is responsible for the breakdown of monoamine NTs
MAO inhibitors work by irreversible binding and inhibiting MAO A and B –> increased availability of monoamine NTs –> increase their release into the synaptic cleft
thus drugs that bind to MAO, since irreversibly bind, could take up to 2 weeks following discontinuation of the drug before the enzyme is resyntheseized to elvels adequate for normal monoamine degradation
Serotonin syndrome
conadministration of SSRI and MAO is contraindicated due to the risk of serotonin syndrome
pontentially fatal condition characterized by restlessness, alt mental status, hyperreflexia and clonus, diaphoresis and tremors
to avoid SS, pt must wait at least 2 weeks after MAO inhibitor discontinuation before initiating SSR therapy, allowing sufficient time fore regeneration of MAO
RA treatment
RA - swelling, pain, morning stiffness in multiple joints > 6 months
RA management = disease-modifying antirhematic drugs, which alleviate pain and inflammation and reduce long-term joint destruction adn disability
includes: methotrexate (first line), sulfasalazine, hydroxychloroquine, minocycline, TNFalpha inhibitors
take weeks
short term tx = anti-inflamatory therapies, such as systemic and intraarticular glucocorticoids, or NSAIDs
Carcinoid Syndrome:
CaRcinoD SSSyndrome
Cutaneous flushing
Right sided heart valvular disease (pathognomonic plaque-like deposits of fibrous tissue on teh right-sided endocardium, causing tricuspid regurg and right-sided heart failure)
Diarrhea (secretory)
Sob / wheezing
Serotonin elevation (excessive serotoning, stimulates fibroblast growth and fibrogenesis –> deposits of fibrous tissue occur most commonly on the endocardium, leading to tricuspid regur, pulmonic valvulopathy, right-sided heart failure – generally only right side of the heart b/c pulmonary vascular endothelial monoamine oxidase inactivate vasoactive products)
5-HIAA (end product of serotonin metabolism), elevated in 24 hour urinary 5-HIAA levels diagnosing suspected carcinoid syndrome
what neurological syndrome can cause wilson’s disease?
cystic degeneration of the putamen
as well as damage to other basal ganglia structures
putamen is located medial to the insula and lateral to the globus pallidus on coronal sections
what is the most common types of RCC
Clear cell CA is the most common subtype of RCC
looks like a bunch of clear cells on imaging!
classic (not really) triad: hematuria, flank pain and palpable abdominal mass w/ constitutional sx
paraneoplastic syndromes due to the secretion of biologically active substance by the tumor cells may also occur - erythrocytosis and polycythemia can occur due to constitutive secretion of erythropoietin, hypercalcemia due to syn of parathyroid hormone-related peptide
metformin MOA and side effects
metformin inhibits hepatic gluconeogenesis and increases peripheral glucose utilization
it inhibits mitochondrial glycerophosphate dehydrogenase and complex I (first electron transport chain enzyme) –> dec in cellular energy stores causes AMPK activation –> dec hepatic gluconeogenesis
INC peirpheral utilization of glucose
lactic acidosis is a rare complication of metformin therapy but its risk is increased in pt with underlying renal insufficiency (measure creatinine!!)
fungal cell wall vs fungal cell membrane
Fungal cell wall is 1,3-beta-D-glucan
(caspofunging and other echinocandin antifungals block glucan syntheiss)
Fungal cell membrane: ergosterol
Amphotericin B and azoles bind to ergosterol in the fungal cell wall inhibit ergosterol synthesis
What are the three phases of acute tubular necrosis:
1. initiation stage: (decreased renal blood flow) ischemic injury to renal tubules precipitated by hemorrhage, acute MI, sepsis, surgery
2. Maintenance stage (24-36 hrs): decreased urine output (oliguria) fluid overload, increasing creatinine/BUN ratio, hyperkalemia
brown cast, low urinary osmo <350, high urinary sodium >30, high urinary fractional sodium excretion FeNa >1
3. Receovery phase: gradual increase in urine output leadign to high volume diuresis. Electrolyte abnormalities may include DEC CONENTRATIONS OF of K, Mg, P04 adn Ca due to slow recovery of tubular fxn
Crohn’s disease:
typically presents with insidious onset of abdominal pain, diarrhea, and constitutional sx
pt are prone to developing fistuals/abscesses as the lesions affect the entire thickness of the bowel wall
perianal (skin tags, fissures) is also common
Can involve the entire GI tract from mouth to anus, spares the rectum
fecal occult blood testing is often positive, however gross blood is less commonly seen unless the colon is involved
prone to developing fistulas and abscesses due to the transmural inflammation that occurs in CD.
Fistulas are abnormal connection btw 2 epithelial-lined organs, usually form btw the bowe and nerby structures that include the skin, urinary bladder, vagina or bowe
What predisposes pt to lymphangiosarcoma?
Lymphangiosarcoma is a malignant neoplasm of the endothelial lining of lymphatic channels
persisten lymphedema (with chronic dilaiton of lumphatic channels) predisposes pt to the development of this malignancy
typical scenario - LS apperance approx 10 years post radical mastectomy for breast CA
CF
CFTR transport of chloride into GI adn respiratory lumens, followed by sodium and water, leading to thin mucus
dyfunction –> dec water within the lum –> thick dehydrated and viscous mucus within organs
recurretn sinopulmonary infections
congenital abscence of vas deferences
pneumonia due to non-lactose fermenting, gram-negative rods (pseudo, burkholderia) very common
Pancreatic insufficiency – duct obstruction, distencious, subseuetn inflammation –> fibrosis (PI usually present at birth in most pt)
inability to absorb fats and fat sol vitamis -> steatorrhea and failure to thrive, req. pacreatin enz supp
