MOD II 2.2 Final

what are the TORCH infections? transmission? symptoms?

• toxoplasma gondii, other (syphilis, parvovirus, VZV, listeria), rubella, CMV, HSV

• direct transplacental, placental damage, delta-maternal, asc. genital tract

• ocular abnormalities, CNS lesion, microcephaly, cardiac issue, skin lesion, skeletal anomalies

  • irreparable → major cause of neonatal morbidity

HSV class, family, identification?

• enveloped dsDNA, herpesviridae

• oral or genital vesicular lesions, keratoconjunctivitis, meningoencephalitis, sepsis, hepatic failure

  • multinucleated giant cell

HHV6&7 class, family, identification?

• enveloped dsDNA, herpesviridae

• exanthem subitum (roseola infantum/6th disease) = maculopapular rash on neck/trunk + high fever (3-4 days); febrile seizure, meningitis, nagayma spots (uvulopalatoglossal spots)

CMV class, family, identification?

• enveloped dsDNA, herpesviridae

• heterophile-negative mononucleosis; microcephaly, PV calcification, jaundice, petechiae/purpura, hepatosplenomegaly, IRGR, sensorineural hearing loss

VZV class, family, identification?

• enveloped dsDNA, herpesviridae

• chicken-pox; limb hypoplasia, cicatricial skin lesions, ocular abnormalities, cortical atrophy

  • multinucleated giant cell

molluscum contagiosum class, family, identification?

• dsDNA virus, poxviridae

• self-limited umbilicated (raised w/ center dimple) papular eruption (2-5 mm); severe = 15+

parvovirus B19 class, family, identification?

• +ssDNA virus, paroviridae (N*)

• nonimmune hydrops fetalis, erythema infectiosum = slapped cheek /5th disease, biphasal, arthralgia; chronic hemolytic anemia, sickle cell, immunodeficiency; infection of seronegative mother = inc. fetal death risk

coxsackievirus (HFM) class, family, identification?

• +ssRNA virus, picornaviridae (N*)

• fever, sore throat, oral cavity lesion (buccal mucosa + tongue), palms + soles

• no vaccine prevention

rubella class, family, identification?

• +ssRNA virus, matonaviridae

• cardiac defect, sensorineural hearing loss, cataracts (white pupils), microcephaly, blueberry muffin rash (discrete maculopapules, face → trunk), hepatomegaly, interstitial pneumonitis, myocarditis, disturb bone growth, IUGR

measles class, family, identification?

• -ssRNA virus, paramyxoviridae

• direct invasion via c. endothelium → SSPE (neurodegeneration via latency), maculopapular rash + koplik spots (mouths), cough, coryza, conjunctivitis

listeria monocytogenes class, family, identification?

• gram+ (purple), rods (anaerobe)

• catalase+, B hemolytic, GI issues, flu-like, abscess, granulomas, meningitis, fetal demise, neo. sepsis

streptococcus agalactiae class, family, identification?

• gram+ (purple), cocci

• catalase-, B hemolytic, fetal demise → abortion/premature/stillbirth, neonatal sepsis, meningitis

toxoplasma gondii class, family, identification?

• protozoa, apicomplexa

• bradyzoites encyst, hydrocephalus, brain calcification/abscess (ring enhancing lesion on CT/MRI), chorioretinitis, lymphadenopathy; death or blindness in pregnancy + AIDs; heterophile negative mononucleosis

mechanical injury (contusion, abrasion, laceration, puncture, incised)?

• impact of force = microvascular injury w/ overlying skin intact → extravasation into adj. tissue

• tangential force across skin, remove epidermal tissue

• tearing tissue w/ tissue bridging → can occur w/ large vessels (deceleration)

• penetration w/ no tissue bridging

• longer than deep w/ no tissue bridging

what to consider in burn wounds? degrees?

• % of body, depth, internal injuries (e.g smoke inhalation)

• superficial (epidermis, red, painful w/ no blisters or scar), partial thickness (dermis, pink, painful w/ blister + wet), full thickness (subcutaneous, white/charred, dry, painless)

causative agents of burn wounds?

• flames (deep), hot solids (contact), hot liquid/steam (scald), electricity (voltage)

• chemicals (acid, alkali)

  • alkali = liquefactive necrosis (deep penetration) → continue damage after exposure (saponification)

  • acid burn = coagulative necrosis (protein denaturation) → local damage

effects of burn wounds?

• systemic inflammation → shock, sepsis, resp. insufficiency

• hypermetabolic state → heat loss + inc. nutritional needs

• hypovolemia + edema (fluid into interstitium)

• site vulnerable to bacteria

• hypertrophic scars via excess collagen

types of ulcerations (venous, diabetic, arterial, pressure)?

• insufficiency → stasis → fibrin deposits + RBC breakdown → skin atrophy → ulcer

  • venous HTN → poor O2 → varicose vein, CHF

• vascular disease (ischemia), neuropathy, systemic metabolic abnormalities, 2ndary infection

• compromised vascularization (atherosclerosis) of peripheral a. → ischemia

• mechanical pressure or local ischemia → tissue compression against bone (heels, post. pelvis, malleoli, greater trochanter)

sarcoma (malignant) morphology? tumor staging?

• fascicular arrangement, spindle cell morphology, marked nuclear atypia

• higher stage = more extensive

  • T= size/organ invasion (1-4, in situ)

  • N = regional LN involvement (0-3)

  • M = metastasis (0= none, 1= present)

adipocyte neoplasm? types of malignant (well-differentiated, myxoid, pleomorphic)

• lipoma

• liposarcoma

  • well-differentiated= indolent, mature adipocyte, atypical spindle cell → MDM2 + CDK4 gene amplification FISH

  • myxoid= abundant matrix → t(2:16) + FUS-DDIT3 gene amplification FISH

  • pleomorphic= aggressive; anaplastic cell, bizarre nuclei, admixed lipoblast → complex karyotype

fibroblast-like neoplasm? types (gardner, superficial, desmoid)?

• fibroma/fibromatosis (bland fibroblasts + dense collagen)

  • gardner → plaque-like sheets w/ few spindle cell (APC mut./FAP)

  • superficial → nodular proliferation (dupuytren, ledderhose)

  • desmoid (abdominal wall mass, post preg) → infiltrative, local/don’t metastasize, CTNNB1 (B-catenin)

• fibrosarcoma → spindle cell w/ herringbone

smooth muscle neoplasm? microscopy?

• leiomyoma (uterine mass) → low mitotic

  • eosinophilic spindle cell, blunt nuclei, SM actin, desmin, caldesmon

• leiomyosarcoma (retroperitoneal) → cigar-shape nuclei, high mitotic, necrosis

skeletal muscle neoplasm? microscopy? sarcoma subtype?

• rhabdomyoma

• rhabdomyosarcoma

  • embryonal (head/neck mass) → primitive round (blue)/spindle

  • alveolar → FOXO1 + PAX3 t(2;13) or PAX7 t(1;13), myogenin immunostain

  • pleomorphic → eosinophilic cytoplasm

  • spindle cell/sclerosing

germline mutation sarcomas?

• neurofibromatosis → NF1 mut. (benign + malignant in nervous/non nervous)

• gardner → APC mut. (familial adenomatous polyposis subtype) = osteomas, desmoid fibromas

• li-fraumeni → TP53 mut. (early onset spectrum of cancer)

• osler-weber-rendu → hemorrhagic hereditary telangiectasia (red speckle)

vascular masses? unknown origin?

• vascular neoplasm → from endothelium or BV support cells

  • benign → kaposi sarcoma via HHV8, epithelioid via WWTR1-CAMTA1 fusion

  • malignant → angio sarcoma w/ endothelial differentiation (post radiation breast)

• vascular malformation → venous, capillary, lymphatic, arterial components

• synovial sarcoma → biphasic (glandular + spindle) + monophasic (only spindle), t(x;18)(p11;q11), TLE1+

4 phases of drug studies?

• drug safety + pharmacokinetics of healthy subjects

• proper dosage + potential efficacy in small group pt. (depends on age, disease, pregnancy, lactation)

• statistical evidence of efficacy + safety in controlled clinical trial

• uncommon + serious adverse effects

  • drug interactions → inhibition/induction of biotransformation

where are weak acids and bases absorbed? overdose treatment? henderson-hasselbalch equation?

• weak acid → stomach

  • aspirin/barbiturate overdose → Tx w/ NaHCO3 (sodium bicarb) → trap in urine

• weak base → intestine

  • amphetamine → Tx w/ NH4Cl (ammonium chloride) → dec. urine pH

• proportion of drug in unchanged state at any pH → predict how much drug can be absorbed

ionized vs non ionized forms of weak acids and bases?

• ionized → water soluble

  • excreted, NOT RA = trapped in renal tubule

  • safe for pregnancy → can’t cross barrier (heparin + propylthiouracil)

• nonionized → lipid soluble (cross cell membrane)

  • secreted + RA in renal tubules and cross BBB (levodopa) and placental barrier

volume of distribution equation? what does an increase mean? loading dose?

• (Vd) = dose/conc. (inherent property)

• drug binds tight w/ tissue → inc. Vd → inc. ½ life

  • higher Vd → higher conc. in extravascular tissue/cells (low Vd = higher conc. in vascular comp)

• loading dose = (Vd)(steady state conc.)/bioavailability

what effects volume of distribution?

• organ blood flow (first to high flow e.g brain), plasma protein binding, molecular size, lipid solubility

  • PBP drugs (bind albumin, a-1 acid, glycoprotein) kept in vascular comp.

  • drugs compete for PBP sites

metabolism (biotransformation) site? phases?

• liver, kidney, skin, gut, lungs

  • toxicity → BM, liver kidney skin

• phase I → ER (oxidation, other rxn)

  • oxidation (ethanol) via CYP450

  • also reduction (nitroglycerine) + hydrolysis (aspirin → salicylate)

• phase II → cytosol (conjugation w/ acetate, glucuronate, sulfate, glycine)

  • also sulfation + methylation

CYP450 inducers?

• griseofulvin, carbamazepine, phenobarbitone/phenytoin, barbiturates, rifampin, st. john’s wort, chronic alcohol etc. (glucocorticoids, nevirapine)

• Guinness, Coronas, PBRS induce Chronic Alcoholism

CYP450 inhibitors (phase I oxidation)?

• ciprofloxacin, ritonavir, amiodarone, cimetidine, ketoconazole, acute alcohol, macrolides, isoniazid, grapefruit juice, omeprazole, sulfonamide, etc. (erythromycin + valproate)

• CRACK AMIGOS

conjugation of phase II metabolism?

• acetylation → speed via genetic polymorphism

  • slow = isoniazid inc. peripheral neuritis; inc. SLE via sulphonamides, hydralazine, isoniazid, procainamide (SHIP)

phase II glutathione conjugation function? example?

• inactivate highly reactive quinone or epoxide intermediate (from certain drugs)

• acetaminophen poisoning → glutathione dec = hepatic tox → Tx w/ N-acetylcysteine (donate SH group + inc. glutathione)

phase II glucuronidation process? enterohepatic cycling function?

• rxn w/ acetate, glucuronate, sulfate, glycine = more water soluble (e.g chloramphenicol) → easier to excrete

• glucuronide conjugate → exc. in bile → hydrolyzed/deconjugated via gut bacteria → lipid soluble= drug RA (e.g OCC)

  • prolongs ½ life + inc. toxicity

what effect do genetic polymorphisms have on metabolism?

• poor CYP2D6 metabolizers = codeine → morphine + tamoxifen → dec. endoxifen (active) → therapeutic failure

• poor CYP2C19 metabolizers = omeprazole cause toxicity → extensive metabolizers need large dose for peptic ulcer Tx

• familial atypical cholinesterase = DOESN’T metabolize succinylcholine (neuromuscular blocking agent)

renal clearance equation? half-life? clearance equation? who has increased sensitivity to therapeutic agents?

• = (renal exc. rate)/(plasma drug conc.)

• time for plasma drug conc. to dec. by 50% (exponential)

• vol. of plasma from which a drug is eliminated per unit of time

  • CL = (0.7 * Vd)/t ½ → t ½ = (0.7 * Vd)/CL

• young or old via dec. capacity to eliminate drugs (target organ more sensitive)

maintenance dose (oral, IV)? infusion rate?

• = (CL * Css/target * dosing interval)/ bioavailability

• = CL * Css/target * dosing interval → bioavailability is 100%

• infusion rate (Ko) = (Css) * CL

first order kinetics? zero order kinetics? how many half lives required in continuous drug administration?

• rate of drug elimination is proportional to plasma drug conc. at any given time

• constant amount eliminated every half-life, when drug elimination mechanisms saturated → PEA (phenytoin, ethanol, aspirin)

• 4-5 ½ lives to reach steady state → rate of drug elimination = rate of drug administration

mosquito class, species? diseases?

• insecta

• aedes, culex, anopheles

• yellow fever, dengue, encephalitis

fleas class, species? diseases?

• insecta

• yersinia pestis, bartonella henselae, rickettsia typhi

• bubonic plague, pruritic, erythematous lesions

lice class, species? diseases?

• insecta

• pediculus humanus var. capitis or corporis and pthirus pubis, borrelia recurrentis, bartonella quintana, rickettsia prowazekii

• itchy/crawling sensation rash

  • Tx scalp w/ topical ivermectin

  • Tx pubic w/ permethrin or piperonyl butoxide

bedbugs class, species? diseases?

• insecta

• cimex lectularius

• larger pruritic, erythematous, raised lesions; linear clusters mostly on neck, torso, arms (hard to tell from flea bites)

ticks class, species? diseases?

• arachnida

• dermacentor variabilis + andersoni, ixodes dammini + scapularis, amblyomma americanum

• tularemia, rocky mountain spotted fever, babesiosis, lyme disease

scabies class, species? diseases?

• arachnida

• sarcoptes scabiei var hominis

• intense pruritis and visible pimple-like rash, web-like pattern (burrows)

chiggers (mites) class, species? diseases?

• arachnida

• larval form of a type of mite (trombiculidae)

• pronounced pruritis, erythematous bite; maybe pustule/blister; mistaken for eczema or contact dermatitis due to scratching

spiders class, species? diseases?

• arachnida

• black widow (latrodectus mactans), hobo (tegenaria agrestis), brown recluse (loxosceles reclusa)

• muscular cramps, chest pains, nausea, vomiting, diaphoresis, intestinal spasms, visual difficulties, spastic cramping → cardiac/resp failure