P450 interactions ending function example

up down -afil erectile dysfunction sildenafil

barbiturates sulfonamides -ane inhalational general anesthetic halothane
neuro drugs are for phenytoin erythromycin -azepam BDZ diazepam
those who act up carbamazepine cimetidine -zolam BDZ alprazolam
griseofulvin ketoconazole inhibits enzyme -azine phenothiazine (neuroleptic, antiemetic) chlorpromazine
ramp up rifampin isoniazid -azole antifungal ketoconazole
chronic EtOH use acute EtOH use -barbital barbiturate phenobarbital
St. John's Wort grapefruit juice -caine local anesthetic lidocaine
quinidine HIV protease inhibitors -cycline protein synth inhibiting abx tetracycline
-etine SSRI fluoxetine
torsades class III, IA -ipramine TCA imipramine
dilated CM doxorubacin (amiodarone), daunarubicin -navir protease inhibitor saquinavir
aplastic anemia chloramphenicol, benzene, NSAIDs, propylthiouracil, methimazole, carbamazepine -operidol butyrophenone (neuroleptic) haloperidol
hemolysis in G6PDD INH, sulfonamides, antimalarials, aspirin, ibuprofen, nitrofurantoin -oxin glycoside (inotrope) digoxin
nephro-/oto-toxic aminoglycosides, cisplatin, vancomycin, loop diuretics -phylline methylxnthine theophylline
disulfiram-like rxn cephalosporins, metronidazole, 1G sulfonylureas (tolbutamide, chlorpropamide), procarbazine -terol β2 ag albuterol
-tidine H2 ant cimetidine
-triptan 5HT1B/1D ag (migrane) sumatriptan
-triptyline TCA amitriptyline
 Micro
Drug Class Use Mechanism SFx/Other
penicillin B-lactam GP (not Staph), Syph Bind PBP, inhibit transpeptidase cross-linking of cell wall, bacteriocidal; G=IV, V=oral; can cause hypersensitivity rxn (all PCNs) or hemolytic
and activate autolytic enzymes anemia, SJS
nafcillin PCNase-resistant S. aureus (not MRSA) Same as PCN, but bulkier R group same as PCN
dicloxacillin PCN, narrow
methicillin spectra + interstitial nephritis
ampicillin aminoPCN, wide certain GPs (Listeria, enterococci) and GNRs (Proteus, Same as PCN, wider spectrum, PCNase sensitive (use with pseudomembranous colitis
amoxicillin spectrum H. flu, E. coli, Salmonella) clavulanic acid) + higher oral availability; rash
ticarcillin extended spectrum Pseudomonas (+AG) and GNR Same as PCN, PCNase sensitive (use with clavulanic acid)
piperacillin PCN Pseudomonas (+AG) and GNR
carbenicillin Pseudomonas (+AG) and GNR
clavulanic acid B-lactamase
sulbactam inhibitor
tazobactam
cefazolin 1G ceph GPC, Proteus, E. coli, K. pneumo (think UTI) B-lactam, but less susceptible to PCN-ases, bactericidal Hypersensitivity (cross hypersensitivity with PCNs in 5-10%), vitamin K deficiency,
cephalexin 1G ceph disulfiram-like rxn with EtOH (only in some cephalosporins), increase nephrotoxicity of
cefoxitin 2G ceph GPC, Proteus, E. coli, K. pneumo, H. flu, Enterobacter, aminoglycosides
cefalcor 2G ceph Neisseria, Serratia (think more UTIs, gonorrhea)
cefuroxime 2G ceph
ceftriaxone 3G ceph H. flu meningitis, Neisseria, gonorrhea prophylaxis for serious gram negative infxn

ceftazidime 3G ceph Pseudomonas

cefipime 4G ceph Pseudomonas and GP
aztreonam monobactam GNRs ONLY, synergistic w/ AGs inhibits cell wall synth (binds PBP3), B-lactamase- no cross-allergenicity w/ PCN or cephalosporins, good in renal insufficiency; occasional
resistant, synergistic w/ AGs GI upset
imipenem/cilastatin carbapenem GPC, GNR, anaerobes; broad spectrum, B-lactamase cilastatin=renal dehydropeptidase I inhibitor, decreases inactivation of drug; seizures, GI distress, rash
meropenem carbapenem resistant dehydropeptidase I stable, lower risk of seizures; GI distress, skin rash
vancomycin glycopeptide GPs ONLY, esp MDR (MRSA, Enterococci, and C. diff) inhibits cell wall mucopeptide formation by binding D-ala rarely SFx: nephrotoxicity + ototoxicity, thrombophlebitis, "red man syndrome"
D-ala portion of precursors (preventable by slow infusion)
gentamicin AG GNR, synergistic w/ B-lactams bind 30S, inhibit initiation complex, cause misreading of nephrotoxic (especially when used w/ cephalosporins), ototoxic (especially when used
amikacin AG GNR, synergistic w/ B-lactams mRNA; require O2 for uptake (no anaerobes); modifying w/ loop diuretics), teratogenic (CN VIII agenesis)
tobramycin AG GNR, synergistic w/ B-lactams transferase enzymes (acetylation, eg) can lead to
resistance
neomycin AG bowel surgery
tetracycline tetracycline I intracellulars: B. burgdorferi, H. pylori, M. pneumo, binds 30S and prevents attachment of AA-tRNA; GI distress, teratogen (teeth discoloration), bone growth inhibition in kids,
Rickettsia, Chlamydia (no CNS penetration) resistance by decreased uptake or increased efflux by hypersensitivity; expired causes Fanconi's, photosensitivity
doxycycline tetracycline pumps (plasmid-encoded); do not take w/ milk, antacids, +fecally eliminated (can be used in pts w/ renal failure)
or Fe (divalent cations inhibit absorption)
demeclocycline tetracycline +ADH antagonist (diuretic in SIADH) +diabetes insipidus
minocycline tetracycline +meningococcal prophylaxis (2nd line)
erythromycin macrolide atypical pneumonia (Legionella, M. pneumo, binds 23S or 50S and inhibits translocation prolonged QT, GI discomfort, acute cholestatic hepatitis (avoid in liver disease),
clarithromycin macrolide Chlamydia), URI, STD, cocci (GP/Neisseria) eosinophilia, skin rashes; P450 down (increases efficacy of theophylline and oral
azithromycin macrolide + MAC prophylaxis (AIDS) anticoagulants)
chloramphenicol meningitis (H. flu, N. meningitides, S. pneumo) inhibits 50S peptidyltransferase; plasmid-encoded anemia (dose dependent), aplastic anemia (dose ind), gray baby sz (in preemies
acetyltransferase inactivates drug because they lack UDP-glucuronyl transferase)
clinda-/linco-mycin lincosamide anaerobes in aspiration pneumonia binds 50S and inhibits translocation pseudomembranous colitis, fever, diarrhea
sulfa- sulfonamide GP, GN, Nocardia, Chlamydia PABA antimetabolytes inhibit DHpteroate synthetase hypersensitivity, SJS, hemolysis (G6PDD), nephrotoxic (tubulo-interstitial nephritis),
SMX sulfonamide I +UTI (DHpteroate=DHF precursor); resistance=all mechanisms teratogen (kernicterus), photosensitive, megaloblastic anemia, P450 down

trimethoprim +SMX UTIs (tx or prophylactic for recurrent), Shigella, bacterial DHFRase I pancytopenia (leuko-, granulocyto-, megaloblastic anemia; may alleviate w/
Salmonella, PCP (tx/prophylaxis) supplemental folinic acid [leucovorin rescue])
nitrofurantoin UTIs (esp E. coli), used in pregnancy bacterial DNA damage can be used in pregnancy, hemolysis in G6PD deficiency
ciprofloxacin FQ GNR (esp of UTI/GI infxn), Neisseria, some GPs topoisomerase II inhibitor; resistance=mutated DNA GI upset, superinfxns, tendonitis/rupture (not for pregnant women/kids), headache,
enoxacin FQ gyrase; do not take w/ antacids dizziness, rash
metronidazole GI protozoa (Giardia, Entamoeba), vaginal free radical toxic metabolites that damage DNA metallic taste, disulfiram-like effect w/ EtOH, headache, mutagenesis
(Trichomonas, Gardnerella), anaerobes
colistimethane polymyxin resistant GNs disrupts membranes (basic cations=detergent) neurotoxic, nephrotoxic (acute tubular necrosis)
dapsone M. leprae (oral, long term), PCP hemolysis (in G6PDD), methemoglobimemia, agranulocytosis
clofazimine M. leprae (added to dapsone)
rifampin M. leprae (delays resistance to dapsone), prophylactic DNA-dep RNA pol inhibitor orange body fluids, minor hepatotoxicity, ups P450
for H. flu and N. meningitides; M. TB (quad tx)

INH (isoniazid) M. TB (quad tx and prophylaxis) decreased synth of mycolic acid, activated by bacterial neurotoxic (seizures), hepatitis, lupus; pyridoxine (B6) can prevent neurotoxicity and
catalase-peroxidase lupus; hemolytic in G6PD deficiency, P450 down
pyrazinamide M. TB (quad tx)
ethambutol M. TB (quad tx)
pentamidine (aerosolized) PCP (prophylaxis, second line, after bactrim)
linezolid VRE binds 50S and inhibits translocation
quinupristin streptogramin VRE
dalfopristin streptogramin VRE
amphotericin B serious systemic mycoses: Histoplasma, Blastomyces, binds ergosterol, forms pores in membrane; does not fever/chills, hypotension, nephrotoxicity (reduced by hydration), arrhythmias, IV
Coccidioides, Aspergillus, Candida, Mucor cross BBB (intrathecal for meningitis) phlebitis, anemia

flucytosine systemic infxn along with Amphotericin B converted to 5-FU, inhibits DNA synth N/V/D/bone marrow suppression, nonmegaloblastic macrocytic anemia
nystatin Candida (thrush, diaper rash, vaginal) same as amphotericin B topical (too toxic for oral)
miconazole azole topical (esp tinea) inhibit fungal ergosterol synthesis by inhibiting P450 liver dysfunction (P450 inhibitor), fever, chills
ketoconazole azole Candida, Histoplasma, Blastomyces, PCOS (hirsutism), enzyme (lanosterol 14-α-demethylase); for systemic + hypocortisolism (blocks hormone synthesis in adrenals), gynecomastia, amenorrhea
Coccidioides, hypercortisolism mycoses; ketoconazole also inhibits human enzyme
desmolase (T-synth)
fluconazole azole Cryptococcal meningitis in AIDS, Candida + can cross BBB
caspofungin Invasive Aspergillosis β-glucan cell wall synthesis inhibitor GI upset, flushing
terbinafine dermatophytes (esp onychomycosis) squaline epoxidase I (ergosterol precursor)
griseofulvin oral tx of superficial infxn, esp dermatophytes (tinea, microtubule inhibitor, deposits in keratin-containing teratogen, carcinogen, confusion, headache, increase P450 and warfarin metabolism
ringworm) tissues
suramin antiprotozoan Trypanosomes, no CNS penetration inhibits energy metabolism enzymes
melacortin antiprotozoan Trypanosomes, CNS penetration inhibits sulfhydryl enzymes
nifurtimox antiprotozoan T. cruzi forms intracellular oxygen radicals
Na stibogluconate antiprotozoan Leishmaniasis inhibits glycolysis at PFK
chloroquine antiprotozoan Plasmodium blocks plasmodium heme polymerase (buildup of toxic hemolytic anemia in G6PD deficiency
mefloquine antiprotozoan Plasmodium (resistant to chloroquine) hemoglobin products)
quinine antiprotozoan chloroquine-resistant Plasmodium (+ pyrimethamine and sulfonamide); Babesia cinchonism (flushing, sweating, headache, confusion, blurred vision, vertigo, tinnitus,
rash, abdominal pain, N/V/D)
pyrimethamine antiprotozoan P. falciparum, + sulfadiazine=toxo inhibits plasmodial DHFRase
mebendazole antihelminth GI, neurocysticercosis inhibits glucose uptake and microtubule synth
albendazole antihelminth Echinococcus inhibits glucose uptake and microtubule synth
pyrantel pamoate antihelminth Enterobius, Ascaris, hookworms stimulates depolarization-induced paralysis by stimulating nicotinic receptors at NMJ
ivermectin antihelminth Onchocerca, Strongyloides amplifies GABA-mediated inhibition leading to immobilization; doesn't cross BBB (no effect on humans)
diethylcarbamazine antihelminth Loa loa, Wuchereria bancrofti, Toxocara canis
praziquantel antihelminth tapeworms and flukes increases membrane permeability to Ca (contraction, paralysis)
amantidine Influenza A (tx and prophylaxis), Parkinson's dz blocks viral penetration/uncoating (M2); also causes ataxia, dizziness, slurred speech
rimantidine release of DA from intact nerves; resistance=mutated M2 doesn't cross BBB, fewer CNS SFx m
(90% of flu A resistant)
zanamivir influenza A and B inhibit neuraminidase
oseltamivir
palivizumab RSV neutralizes F-protein
ribavirin RSV, chronic hep C inhibit IMPDH (guanine synthesis) hemolytic anemia, teratogen (severe)
acyclovir HSV (tx and prophylaxis), VZV, EBV guanosine analog: monophosphorylated by viral no effect on latent virus; resistance=lack of viral thymidine kinase
famciclovir herpes zoster thymidine kinase, triphosphate made in human cells;
gangciclovir CMV (mostly in immunocompromised) leads to chain termination thrombocyto-/leuko-/neutro-penia, nephrotoxic
foscarnet gangciclovir-resistant CMV retinitis, acyclovir-resistant viral DNA pol inhibitor, binds to PP-binding site, no nephrotoxic, hypo-Ca/PO4/K/Mg; resistance by mutated DNA pol
HSV activation required
saquiNAVIR protease I HIV prevents cleavage of polypeptide products of pol gene, hyperglycemia, N/D, lipodystrophy, P450 inhibition
indiNAVIR protease I HIV thus inhibiting virion assembly + thrombocytopenia
stavudine (d4T) nucleoside reverse HIV competitively inhibit nucleotide binding site on RT causing bone marrow suppression (can be reversed with GCSF and erythropoietin), peripheral
zalcitabine (ddC) transcriptase HIV DNA chain termination; must be activated first by viral neuropathy, lactic acidosis
didanosine (ddI) inhibitor HIV thymidine kinase + pancreatitis
zidovudine (ZDV) HIV (tx, prophylaxis, pregnancy) + megaloblastic anemia
nevirapine NNRTI HIV bind to RT at site different from NRTIs, do not require bone marrow suppression (can be reversed with GCSF and erythropoietin), peripheral
efavirenz NNRTI HIV phosphorylation neuropathy, rash (SJS)
delaviridine NNRTI HIV
enfuvirtide fusion inhibitor HIV (used in pts w/ persistent viral replication despite bind gp41: inhibit conformational change necessary for hypersensitivity, increased risk of bacterial pneumonia
HAART) fusion with CD4 cells
IFN-α recombinant chronic hep B/C, Kaposi's sarcoma, leukemias, synthesized by viral infected cells to block replication of neutropenia
malignant melanoma DNA and RNA viruses
IFN-β recombinant MS neutropenia
IFN-γ recombinant NADPH oxidase deficiency neutropenia
Immune
Drug Class Mechanism Use SFx/Other
cyclosporine Binds cyclophilins, inhibits calcineurin preventing IL-2 some autoimmune disorders, suppresses organ rejection nephrotoxic (prevented by mannitol diuretic), higher risk for viral infxn and lymphoma
and IL-2R production
tacrolimus Binds FK-BP, inhibits IL-2 and IL-2R production (and suppresses organ rejection (very strong significant: hyperglycemia, htn, nephrotoxicity, peripheral neuropathy, pleural effusion
other cytokines) immunosuppressant)
sirolimus (rapamycin) inhibits mTOR and TC response to IL-2 kidney transplant (+ cyclosporine and steroids) hyperlipidemia, thrombocytopenia, leukopenia
daclizumab MAb w/ high affinity for IL-2R on activated TC kidney transplant
azathioprine antimetabolite precursor to 6-MP (interferes w/ kidney transplant, autoimmune disorders (including GN, bone marrow suppression, worsened w/ allopurinol (6-MP broken down by xanthine
nucleic acid synth) hemolytic anemia, UC) oxidase), nonmegaloblastic macrocytic anemia
muromonab-CD3 (OKT-3) MAb that binds CD3 (epsilon chain) on TC, blocks signal kidney transplant cytokine release syndrome, hypersensitivity rxn
transduction
aldesleukin recombinant IL-2 RCC, metastatic melanoma
erythropoietin recombinant epoetin anemias (esp renal failure)
filgrastim recombinant Granulocyte Colony Stimulating Factor bone marrow recovery
sargramostim recombinant Granulocyte/Macrophage-CSF bone marrow recovery
oprelvekin recombinant IL-11 thrombocytopenia
thrombopoietin recombinant thrombopoetin thrombocytopenia
digoxin immune Fab therapeutic ab antidote for digoxin intoxication
Pharm/Cardio
Drug Class Mechanism Use SFx/Other
metyrosine inhibits tyrosine hydroxylase (makes DOPA) htn from pheo (prevents catecholamine synth)
guanethidine inhibits NE release (replaces it in vescicles) htn
bethanechol direct ACh ag ACh ag, resistant to AChE neurogenic ileus/urinary retention and postop exacerbation of COPD/asthma (M3), and peptic ulcers (M1 and M3); severe/OD on
neostigmine AChEI no CNS penetration neurogenic ileus/urinary retention and postop (reversal of AChEI: DUMBBELS=diarrhea, urination, miosis, bradycardia, bronchospasm, excitation
NMJ block), myasthenia gravis of CNS and skeletal mm, lacrimation, sweating, salivation
edrophonium AChEI no CNS penetration, extremely short acting dx of myasthenia gravis
pyridostigmine AChEI no CNS penetration, long acting tx of myasthenia gravis
physostigmine AChEI CNS penetration glaucoma and atropine OD
atropine ACh ant regenerates AChE causes mydriasis and cycloplegia, tx of ACh poisoning constipated, urine retention, mydriasis, cyclopegia, acute angle closure glaucoma,
(organophosphates) bronchodilation, tachycardia, disorientation, increased T, and dry eyes, skin, and mouth
pralidoxime regenerates AChE with atropine, for cholinesterase poisoning (hot, dry, red, blind, mad, all analogies)
scopolamine ACh ant CNS motion sickness tx OD w/ physostigmine salicylate
oxybutynin ACh ant GU reduce urgency in mild cystitis and reduce bladder spasms
glycopyrrolate ACh ant
hexamethonium nicotinic ag ganglionic blocker used in experiments only severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction
epinephrine Symp ag vasoconstriction decreases aq humor production; low anaphylaxis, open angle glaucoma, asthma, hypotension DON’T use in closed angle: causes mydriasis and can block angle more
dose: β>α; high: α>β
NE Symp ag α>β1 hypotension (but decreases renal perfusion)
DA Symp ag D>β>α, inotropic and chronotropic shock (increases renal perfusion), CHF
dobutamine Symp ag β1>β2, inotropic CHF, cardiac stress testing
phenylephrine Symp ag α1>α2 pupillary dilation, vasoconstriction, nasal decongestion
ephedrine release stored catecholamines nasal decongestant, urinary incontinence, hypotension tachyphylaxis (rebound congestion/continence[?])
cocaine catecholamine reuptake inhibitor, inactivates Na causes vasoconstriction, local anesthesia fetal abnormalities, fetal addiction, placental abruption, coronary vasospasm; OD: pupil
channels dilation, hallucinations (esp tactile), paranoia, angina, tx=BDZ; withdrawal: suicidal,
hypersomnolent, malaise
clonidine central α2 ag, decrease central adrenergic outflow htn, esp. in renal disease (no decrease in renal blood
α-methyldopa flow), DM, 1st line in preg (+ hydralazine) direct Coombs-positive hemolytic anemia
ergonovine peripheral alpha agonist (and DA, 5HT) dx of Prinzmetal's angina, placental delivery ergotism
phenoxybenzamine irreversible nonselective α-blocker pre-op on pheo orthostatic hypotension, reflex tachycardia
phentolamine reversible nonselective α-blocker
(praz)-osin α1-blocker (smooth m relaxation) htn, urinary retention in BPH 1st dose orthostatic hypotension, dizziness, headache
carvedilol nonselective α- and β-blocker htn (decrease CO, decrease renin secretion [β blockade on impotence, exacerbation of asthma, CV effects (bradycardia, AV block, CHF), CNS
labetalol nonselective α- and β-blocker JGA cells]), angina (decrease afterload, decrease HR and effects (sedation, sleep alteration), caution in DM (tx OD w/ glucagon), partial agonists
nadolol nonselective β-blocker contractility [via calcium channels] causing decreased O2 (pindolol and acebutolol) contraindicated in angina; metoprolol can cause dyslipidemia
consumption), MI and CHF (decrease mortality [esp
pindolol nonselective partial β-agonist
carvedilol], slow progression), glaucoma (timolol, carve-
acebutolol β1 partial agonist (>β2)
dilol, betaxolol, decrease secretion of aqueous humor),
betaxolol selective β1-blocker antiarrhythmics (SVT, VT, AFib; decrease cAMP, Ca
propranolol AND class II anti- nonselective β-blocker currents, and AV conduction velocity, increase PR); mnemonics class II antiarrhythmics: help with Most suPrAvEnTriculars= metoprolol,
timolol arrhythmics nonselective β-blocker headache, essential tremor (propranolol) propranolol, atenolol, esmolol, timolol; Partial agonists: pindolol, acebutolol; selective
esmolol selective β1-blocker, short-acting β1: A-M (atenolol, acebutolol, betaxolol, esmolol, metoprolol); nonselective: N-Z
(nadolol, pindolol, propranolol, timolol)
atenolol selective β1-blocker
metoprolol selective β1-blocker
hydralazine vasodilator increased cGMP, relaxing smooth m; arterioles>veins, htn in pregnancy (1st line, with methyldopa), severe htn, reflex tachycardia (contraindicated in angina/CAD, commonly given w/ β-blocker),
afterload reduction CHF Lupus-like sz
verapamil (non-DHP) (L-type) CCB and reduce mm contractility, ventricle>>vessels; β-blocker- htn, angina (no unstable for DHP), Raynaud's, arrhythmias cutaneous flushing, cardiac depression, AV block (careful in WPW), peripheral edema,
type IV like antianginal (non-DHPs; nodal arrhythmias [SVT, AFib]: slow dizziness, constipation, gingival hyperplasia
diltiazem (non-DHP) antiarrhythmic reduce mm contractility, ventricle=vessels conduction velocity, increase refractory period and PR,
decrease slope of phases 1 and 2)
nife-/amlo-dipine (DHP) (L-type) CCB vasodilator, ventricle<<vessels; nitrate-like antianginal + peripheral edema, reflex tachycardia
(little effect on contractility)
nitroglycerin venodilator release NO in smooth m causing increased cGMP, angina, pulmonary edema, aphrodisiac, erection reflex tachycardia, hypotension, flushing, dizziness, headache (esp in industrial
isosorbide dinitrate venodilator veins>aa, decrease preload enhancer, esophageal spasm exposure: "Monday Dz", tolerance common)
nitroprusside short acting, same as nitroglycerin malignant htn cyanide toxicity
fenoldopam D1 ag, relaxes renal vascular smooth m malignant htn
diazoxide K-ch opener hyperpolarizes/relaxes vascular smooth m malignant htn, insulinoma hyperglycemia (reduces insulin release)
-statin HMG-CoA RI inhibits chlsl to mevalonate lower LDL>>TG, raise HDL a little hepatotoxicity, rhabdomyolysis
niacin (also see vitamin B3 decreases hepatic VLDL secretion into circ, inhibit lower LDL>TG, raise HDL a bunch cutaneous flushing (esp face), hyperglycemia, acanthosis nigricans, hyperuricemia
section) lipolysis in adipose tissue
cholestyramine bile acid resin prevents intestinal reabs of bile acids, liver uses chlsl to lower LDL, slightly raise HDL and TG pts hate it: tastes bad, constipation, decreased abs of fat soluble vitamins, chlsl
colesevelam make more gallstones
ezetimibe prevents chlsl reabs at small intestine brush lower LDL rare increase in LFT
gemfibrozil fibrate upregulate LPL causing increased TG Cl. lower TG>>>LDL, raise HDL a little myositis, hepatotoxicity (LFT), chlsl gallstones
digoxin cardiac glycoside gynecomastia, cholinergic (N/V/D), blurry yellow vision, ECG (high PR, low QT,
inhibition of Na/K ATPase causes indirect inhibition of CHF (decrease morbidity, not mortality), AFib (depresses scooping, inverted-T, arrhythmia), hyperK; OD worse w hypoK, renal failure, and
Na/Ca exchanger, increases [Ca]i, positive inotropy; SA node, slow AV nodal conduction); 75% bioavailable, quinidine (decreased clearance); tx OD w/ digoxin immune Fab, slowly normalize K,
stimulates vagus (suppresses AV node) 20-40% protein bound, t1/2=40h, urinary excretion lidocaine, cardiac pacer, Mg
class I antiarrhythmics Na ch blockers affect on AP: phase 1=BAC (B is unchanged); phase mnemonic: Double Quarter Pounder, Lettuce Tomato toxicity increased w/ hyperkalemia
3=BCA (C is unchanged) Mayo, Extra/More Fries Please
disopyramide class IA anti- increase AP duration, effective refractory period, and good for atrial and ventricular arrhythmias, especially
quinidine arrhythmics QT; big gap in phase 3 from normal; intermediate reentrant and ectopic SVT, and VT Torsades, cinchonism (tinnitus, headache), thrombocytopenia
dissociation speed
 class IA anti- increase AP duration, effective refractory period, and good for atrial and ventricular arrhythmias, especially
arrhythmics QT; big gap in phase 3 from normal; intermediate reentrant and ectopic SVT, and VT
procainamide dissociation speed Lupus-like sz
mexiletine class IB anti- decrease AP duration (no effect on QRS), preferentially acute ventricular arrhythmias (esp post-MI) and digitalis- CNS stimulation/depression, CV depression
lidocaine arrhythmics target ischemic/depolarized Purkinje/ventricular induced arrhythmias (lidocaine)
tocainide tissue; fast dissociation
moricizine/encainide class IC anti- no effect on AP duration, slow dissociation, so VT (esp that go to VFib), intractible SVT, last resort in proarrhythmic, esp post MI (contraindication)
flecainide arrhythmics significantly prolongs refractory period in AV node refractory tachyarrhythmias, only in pts w/o structural
propafenone abnormalities
sotalol class III anti- increase AP duration, increased effective refractory used when other arrhythmics fail; amiodarone has class I, Torsades, excessive β-block
ibutilide arrhythmics: K- period, and increased QT interval; big gap in phase 3 II, III, and IV effects bc it alters the lipid membrane torsades
bretylium channel blockers from normal; sotalol is also mild beta blocker new arrhythmias, hypotension (emergency use only)
dofetilide
amiodarone pulmonary fibrosis, hepatotoxicity, thyroid dysfunction (40% I by wt), hypersensitivity,
corneal deposits, photodermatitis, blue/gray skin deposits, CNS effects, constipation,
CV effects (bradycardia, heart block, CHF, NOT TORSADES)

adenosine antiarrhythmic transient AV block (A1R=Gq); endothelial dependent dx/tx of SVT, dx of CAD, very short acting (~15s) cutaneous flushing, hypotension, chest pain (blocked by theophylline)
smooth m relaxation
K antiarrhythmic depress ectopic pacemakers in hypokalemia digoxin toxicity
Mg antiarrhythmic torsades and digoxin toxicity
Endocrine
Drug Class Mechanism Use SFX/other
bromocriptine DA ag, inhibits PRL secretion PRLoma, Parkinsons, neuroleptic malignant sz
cabergoline DA ag, inhibits PRL secretion PRLoma
methimazole inhibits peroxidase-coupling of MIT/DIT and thyroid hyperthyroidism skin rash, aplastic anemia, agranulocytosis (rare)
propylthiouracil hormone synthesis + hepatotoxicity
octreotide somatostatin analog (in stomach, inhibit ECL cell GHoma, NET, gastrinoma, glucagonoma, acute variceal nausea, cramps, steatorrhea
secretion of histamine) bleed, VIPoma, carcinoid tumor
desmopressin (ddAVP) ADH analog; releases endothelial vWF store central DI, von Willebrand's dz given intranasal for DI
lispro rapid-acting insulin bind insulin receptor; liver: increased glycogen DM, gestational DM, life-threatening hyperkalemia, hypoglycemia, hypersensitivity (very rare)
aspart (SPeedy) synthesis; muscle: increased glycogen and protein stress-induced hyperglycemia
insulin synthesis, K uptake; fat: aids TG storage
NPH intermediate
glargine long-acting insulin
detemir
tolbutamide 1G sulfonyl-urea close K-channel in β-cell membrane, causes cell T2DM (stimulates endogenous release of insulin, need disulfiram-like effect w/ EtOH, hypoglycemia
chlorpropamide depolarization and triggers Ca influx and insulin release some β-cell function, so useless in T1DM)
glyburide 2G sulfonyl-urea hypoglycemia
glimepiride
glipizide
metformin biguanide decreases gluconeogenesis, increase glycolysis and oral, can be used in pts w/o islet function (T1 or 2DM) lactic acidosis (contraindicated in renal failure)
peripheral glucose uptake
pioglitazone thiazolidine-diones increase peripheral insulin sensitivity, binds PPAR-γ T2DM (monotherapy or combo) weight gain, edema, hepatotoxicity, CV toxicity
rosiglitazone
acarbose α-glucosidase inhibit intestinal brush border enzymes, delays sugar T2DM (monotherapy or combo) diarrhea
miglitol inhibitor hydrolysis/absorption
pramlintide amylin mimetic decrease glucagon T2DM hypoglycemia, N/D
exenatide GLP-1 analog increse insulin, decrease glucagon T2DM N/V, pancreatitis
levothyroxine thyroxine replacement hypothyroidism, myxedema tachycardia, heat intolerance, tremors, arrhythmias
triiodothyronine
GH hormone replacement GH deficiency, Turner's
oxytocin hormone replacement stimulates labor, uterine contractions, milk let-down, controls uterine hemorrhage
hydrocortisone synthetic inhibits virtually all cytokines by inactivating NF-κB Addison's, inflammation, immune suppression (Crohn's), iatrogenic Cushing's (incl. osteoporosis [contraindication], peptic ulcers, and DM),
beclomethasone glucocorticoid (TNF-α transcription factor) asthma (1st line for chronic) adrenal insufficiency when drug stopped after chronic use
dexamethasone + dx of Cushing's dz (suppression test)
 synthetic iatrogenic Cushing's (incl. osteoporosis [contraindication], peptic ulcers, and DM),
glucocorticoid adrenal insufficiency when drug stopped after chronic use

prednisone + triggers apoptosis + CLL, Hodgkins

GI
Drug Class Mechanism Use SFX/other
methscopolamine ACh ant block M1R on ECL cells (decrease histamine) and M3R peptic ulcers (rarely used) tx OD w/ physostigmine salicylate; tachycardia, dry mouth, difficulty focusing eyes
pirenzepine ACh ant on parietal cells (decrease H secretion)
propantheline ACh ant
famoTIDINE reversible block of H2R on gastric parietal cells causes PUD, gastritis, mild esophageal reflux none (most H2 blockers); cimetidine: P450 down, gynecomastia (antiandrogenic, PRL
raniTIDINE decreased H secretion (cimetidine=also release, impotence, decreased libido), can cross BBB (confusion, dizziness, headaches);
cimeTIDINE antiandrogenic) ranitidine and cimetidine: decrease renal excretion of creatinine
nizaTIDINE
omeprazole PPI irreversibly inhibit H/K ATPase in parietal cells PUD, gastritis, esophageal reflux, Zollinger-Ellison Sz, H.
lansoprazole pylori (+ clari, metro/amoxi)
bismuth bind to ulcer base, provides physical protection, allows improved ulcer healing, traveller's diarrhea, + black tongue, stool
sucralfate HCO3 secretion metronidazole + amoxicillin (or tetracycline) for H. pylori

misoprostol PGE1 analog, increased production of gastric mucous, prevention of NSAID-induced ulcer, induce labor, diarrhea, abortifacient
decreased H+ production maintenance of ductus arteriosus
Al(OH)3 antacid can affect absorption, bioavailability, and excretion of all cause hypokalemia constipation, hypophosphatemia, mm weakness, osteodystrophy, seizure
Mg(OH)2 other drugs (alters pH or delaying gastric emptying) diarrhea, hyporeflexia, hypotn, cardiac arrest
CaCO3 hyperCa, rebound acid level, chelates other drugs
sulfasalazine sulfa- antibiotic + 5-aminosalicylate (anti- UC, Crohn's malaise, nausea, sulfa, reversible oligospermia
inflammatory), activated by bacteria
etanercept recombinant form of TNF-R (sequesters TNF) Crohn's, RA, psoriatic arthritis
adalimumab therapeutic ab anti-TNF-α Crohn's, RA, psoriatic arthritis
infliximab therapeutic ab anti-TNF-α Crohn's, RA, psoriatic arthritis, ankylosing spondylitis respiratory infxn (reactivation of latent TB bc TNF-α maintains granulomas), fever,
hypotension
ondansetron 5HT3 ant, powerful central antiemetic decrease vomiting (post-op, chemo) headache, constipation
metoclopramide D2R ant causes increased LES tone, motility, antiemetic, gastroparesis (DM or post-surgery), does not Parkinsonian, restlessness, drowsiness, depression, N/D; interacts w/ digoxin and
contractility, decreased pyloric S tone influence colon transport time diabetic agents; contraindicated in SI obstruction
Heme/Onc
Drug Class Mechanism Use SFX/other
heme and glucose inhibits ALA synthase (RLS of heme synth) acute intermittent porphyria
vitamin A (xs) for PML: inhibits retinoic acid receptor causing acne, measles, PML (AML M3) teratogen (spontaneous abortion, cleft palate, cardiac abnormalities); when txing PML,
promyelocyte differentiation can release Auer rods and cause DIC
heparin immediate anticoagulation: PE, CVA, acute coronary sz, follow PTT; bleeding, thrombocytopenia/clotting (HITT, binds PF4 [platelet factor 4,
activates antithrombin, acts most on Xa and thrombin; MI, DVT; safe for pregnancy natural CXCR4L]), osteoporosis; antidote= protamine sulfate (positive, binds)
very short t1/2; watch PTT

enoxaparin LMW heparin acts more on Xa, better bioavailability, longer t1/2; not easily reversible, similar sfx
subQ, fine if unmonitored
(bival)-IRUDIN hirudin directly inhibit thrombin heparin alternative in pts w/ hx of HIT
warfarin inhibit activation (γ-carboxylation) of vit K-dependent chronic anticoagulation, oral monitor PT, metabolized by P450; antidote=vitamin K; for more rapid reversal, give
facotrs (II, VII, IX, X, proteins C and S) FFP; skin/tissue necrosis; teratogen (bone deformities, fetal hemorrhage, abortion)

tPA convert plasminogen to plasmin, which degrades early MI, early ischemic stroke bleeding, treat toxicity with aminocaproic acid or tranexamic acid (plasminogen
urokinase fibrinogen and fibrin activation inhibitors)
streptokinase bind w/ plasminogen, activate plasminogen
anistreplase streptokinase bound to plasminogen
clopidogrel binds ADPR on platelets, inhibits GpIIb/IIIa expression, acute coronary sz, coronary stenting, decrease risk of
ticlopidine inhibits fibrinogen binding thrombotic stroke neutropenia
abciximab therapeutic ab GpIIb/IIIa Ab for activated platelets prevent cardiac ischemia in unstable angina and in pts bleeding, thrombocytopenia
txed w/ percutaneous coronary intervention, acute
coronary sz
methotrexate (MTX) antimetabolite (all folic acid analog, inhibits DHFR, decreasing dTMP and leukemia, lymphoma, chorioca, sarcomas; abortion, myelosuppression (leucovorin rescue), macrovescicular fatty liver, mucositis (aphthous
work on S-phase) DNA/protein synth ectopic pregnancy, RA, psoriasis ulcer), teratogenic; tx OD by alkalinizing urine
 antimetabolite (all
work on S-phase)
5-FU pyrimidine analog, activated to 5F-dUMP, covalently solid tumors, topical for basal cell ca, synergistic w/ MTX myelosuppression (non-megaloblastic microcytic anemia, thymidine rescue),
binds DHFR, which inhibits thymidylate synthase, photosensitivity
decreasing dTMP
6-MP purine analog, inhibits de novo purine synth, activated leukemia or lymphoma (not CLL or HL), UC nonmegaloblastic macrocytic, GI, liver; increased toxicity w/ allopurinol
6-thioguanine (6TG) by HGPRT ALL marrow depression, can be given w/ allopurinol
cytarabine (ara-C) pyrimidine analog, inhibits DNA Pol AML, ALL, high grade NHL leukopenia, thrombocytopenia, megaloblastic anemia
dactinomycin antitumor abx intercalates in DNA Ewing's sarcoma, rhabdomyosarcoma, childhood tumors myelosuppression
(mostly G2) (Wilm's)
doxorubicin (adriamycin) anthracyclines: noncovalently intercalate in DNA Hodgkins, myelomas, sarcomas, solid tumors cardiotoxicity (dilated CM, protected by dexrazoxane [Fe-chelation]),
causing breaks; generate free radicals myelosuppression, alopecia; toxic to tissues with extravasation
daunorubicin
bleomycin free radical formation, breaks DNA testicular and Hodgkins pulmonary fibrosis, skin changes, minimal myelosuppression
(eto)-POSIDE (VP-16) inhibits topoisomerase II (S and G2) SCC of lung/prostate, testicular myelosuppression, GI irritation, alopecia
nitrosurea (- alkylating agents require bioactivation, cross BBB brain tumors (including glioblastoma multiforme) CNS toxicity; all alkylating agents: teratogen (missing digits), aplastic anemia
mustines)
cyclophosphamide covalently cross-link DNA at guanine N7, require NHL, breast, ovarian; also good immunosuppressants myelosuppression, hemorrhagic cystitis (lessened by mesna, better control w/
ifosfamide activation by liver ifosfamide); SIADH for cyclophosphamide
procarbazine alkylates DNA Hodgkin's, brain tumors disulfiram-like effect w/ EtOH
busulfan alkylates DNA CML, pre-marrow-transplant marrow ablation pulmonary fibrosis, hyperpigmentation
vincristine microtubule bind tubulin, block polymerization, inhibit mitotic Hodgkins, Wilm's, chorioca neurotoxic (areflexia, peripheral neuritis), paralytic ileus
vinblastine inhibitor (M-phase) spindle formation bone marrow suppression
paclitaxel hyperstabilize polymerized microtubules, inhibit ovarian and breast myelosuppression, hypersensitivity
-TAXOLs mitotic spindle degradation
(cis/carbo)-PLATIN cross-link DNA testicular, bladder, ovary, lung nephrotoxic, ototoxic
amifostine cytoprotective free radical scavenger prevent nephrotoxicity and xerostomia, given with
platinum and alkylating agents
hydroxyurea (S-phase) ribonucleotide reductase inhibitor melanoma, CML; sickle-cell (increase HbF) nonmegaloblastic macrocytic anemia, GI upset
trastuzumab (herceptin) therapeutic ab Ab against HER-2 (erb-B2); possibly kills through Ab- HER-2-overexpressing breast cancer cardiotoxic
dependent cytotoxicity
imatinib (Gleevec) NOT AN Ab bcr-abl tyrosine kinase inhibitor CML (Philadelphia chr., main target), GIST fluid retention
rituximab therapeutic ab Ab against CD-20 (on most BC neoplasms) BC non-Hodgkin's lymphoma, RA (+ MTX)
Musculoskeletal
Drug Class Mechanism Use SFX/other
aspirin (ASA) NSAIDs irreversibly acetylates COX (1 and 2), prevents low dose (<300mg/day, TXA2): antiplatelet; intermed dose all NSAIDs: inhibit dilation of afferent arteriole, drop GFR (acute renal failure),
conversion of AA to TXA2, PGE2, PGI2 (300-2400mg/day, PGE2): antipyretic and analgesic; high intersitial nephritis, gastric upset/ulceration/bleed, and aplastic anemia; hemolytic
dose (2400-4000mg/day): anti-inflammatory anemia in G6PDD, CN VIII issues, mixed RAlk (hyperpnea) and MAc; Reye's syndrome in
kids (esp w/ viral infxn)
ibuprofen reversibly inhibit COX (1 and 2), blocks prostaglandin antipyretic, analgesic, anti-inflammatory, acute gout (w/ all NSAIDs: inhibit dilation of afferent arteriole, drop GFR (acute renal failure),
naproxen synthesis; COX-1 maintains gastric mucosa, COX-2 in colchicine, esp indomethacin), migranes intersitial nephritis, gastric upset/ulceration/bleed, and aplastic anemia; fluid
ketorolac inflammatory cells and vascular endothelium retention; ibuprofen: hemolytic anemia in G6PDD
indomethacin + induces closure of PDA, nephrogenic DI
celecoxib reversibly inhibit COX-2 RA, OA, pts w/ gastritis/ulcers higher risk of thrombosis, sulfa allergy, lower incidence of GI sfx
acetaminophen reversibly binds COX, mostly in CNS (peripherally antipyretic, analgesic, NO anti-inflammatory no Reye's sz, but OD causes hepatic necrosis (metabolyte depletes glutathione and
inactivated) forms toxins in liver), N-acetylcysteine is antidote; chronic use can cause renal papillary
necrosis
(etid)-RONATE bisphos-phonates inhibits osteoclast activity, reduce resorption + malignancy-associated hypercalcemia, Paget's dz of bone, corrosive esophagitis, N/D, osteonecrosis of jaw
zoledronate (IV) formation of hydroxyapatite postmenopausal osteoporosis no corrosive esophagitis (IV)
colchicine binds and stabilizes tubulin, impairing chemotaxis and acute gout (with NSAIDs, esp indomethacin) GI side effects, agranulocytosis
degranulation
probenecid inhibits reabsorption of uric acid in PCT, inhibits chronic gout, also given w/ PCN to prolong t1/2 sulfa allergy
secretion of PCN
allopurinol inhibits xanthine oxidase, decreased conversion of chronic gout; lymphoma/leukemia w/ chemo to prevent SJS, increases concentrations of azathioprine and 6-MP (both metabolyzed by xanthine
xanthine to uric acid tumor lysis urate nephropathy oxidase, give 6-tG instead of 6-MP)
Neuro
Drug Class Mechanism Use SFX/other
riluzole decreases presynaptic glutamate release ALS
latanoprost PGF2a (increases outflow of aq humor) glaucoma darkens iris
brimonidine α ag (think clonidine) glaucoma
carbachol direct ACh ag contract ciliary m, increase aq humor outflow glaucoma, causes miosis, relieve IOP exacerbation of COPD, asthma, and peptic ulcers; severe/OD on AChEI:
pilocarpine direct ACh ag + AChE resistant, more potent glaucoma emergency, ups sweat, tears, saliva DUMBBELS=diarrhea, urination, miosis, bradycardia, bronchospasm, excitation of CNS
echothiophate AChEI CNS penetration glaucoma and skeletal mm, lacrimation, sweating, salivation
tropicamide ACh ant in eye causes mydriasis and cyclopegia
morphine opioid, μR decrease synaptic transmission by opening K-ch and pain, acute pulmonary edema Respiratory depression, miosis (pinpoint pupils), additive CNS depression with other
codeine opioid closing Ca-ch; inhibits release of ACh, NE, 5HT, glu, drugs (EtOH, BDZ, barbiturates, 1B antiarrhythmics), addiction, constipation, N/V;
heroin opioid substance P; induces NO synthase expression, lowers tolerance does not develop to miosis and constipation; do not use morphine in renal
preload failure, acute respiratory depression, high ICP (can worsen respiratory depression),
meperidine opioid
biliary colic
dextromethorphan opioid + cough suppression
-OD (life-threatening) txed w/ naloxone or naltrexone (opioid ant)
loperamide opioid + diarrhea (no CNS sfx) -withdrawal: flu-like (sweating, dilated pupils, piloerection ["cold turkey"], fever,
diphenoxylate opioid + diarrhea (CNS sfx) rhinorrhea, N/D/stomach cramps); symptomatic tx
fentanyl opioid (stronger than morphine) -heroin: high risk for hepatitis, abscess, OD, hemorrhoids, AIDS, RHF -
methadone opioid (partial ag, long acting) heroin detox meperidine: risk for seratonin sz w/ MAOI and SSRIs
enkephalin opioid, δR endogenous
dynorphin opioid, κR endogenous
tramadol opioid very weak opioid, SNRI chronic pain similar to opioids, decreases seizure threshold
butorphanol opioid opioid, partial agonist at μ-R, agonist at κ-R pain less respiratory depression, causes withdrawal if on full ag
buprenorphine opioid opioid, partial ag pain, opioid addiction, used w/ naloxone
phenytoin also IB anti- increased Na channel inactivation (increased refractory seizures (all but absence), first line for tonic clonic or Lupus-like sz, SJS, peripheral neuropathy, megaloblastic anemia (low folate absorption),
arrhythmic period), inhibits presynaptic excitatory glutamate status seizure prophylaxis, arrhythmias (IB) nystagmus, diplopia, ataxia, sedation, teratogen (fetal hydantoin sz=IUGR), gingival
fosfentoin parenteral release hyperplasia, hirsutism, P450 up
carbamazepine mood stabilizer increased Na channel inactivation partial, tonic clonic (1st line), trigeminal neuralgia (1st diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity,
line), bipolar teratogenic, P-450 induction, SIADH, SJS
lamotrigine blocks voltage-gated Na channels partial and tonic clonic SJS
gabapentin CCB (designed as GABA analog) partial and tonic clonic, peripheral neuropathy, bipolar sedation, ataxia

topiramate blocks Na channels, propagates GABA action partial and tonic clonic sedation, mental dulling, kidney stones, weight loss
phenobarbital barbiturate propagates GABAA action by increasing duration Cl partial + tonic clonic (esp in pregnancy/kids), anxiety, sedation, tolerance, dependence, P-450 induction (contraindicated in porphyria), CNS
channel is open insomnia, Crigler-Najjar Sz type II depression (additive w/ EtOH), SJS; OD: respiratory/ cardiac depression (can cause
thiopental barbiturate (IV) high potency, highly lipid soluble; decreases cerebral induction of anesthesia (decrease cerebral blood flow) death), supporative tx and HCO3- (alkalinize urine); withdrawal: delerium, CV collapse
blood flow (life-threatening)
valproate mood stabilizer increased Na channel inactivation, increase GABA seizures (all but status, first line in tonic clonic), myoclonic GI distress, hepatotoxicity/necrosis (can be fatal, measure LFTs), teratogen (neural tube
concentration seizures, bipolar defects), tremor, weight gain
ethosuximide blocks thalamic T-type Ca channels absence (first line) fatigue, GI distress, headache, urticaria, SJS
tiagabine inhibit GABA reuptake partial seizures
vigabatrin irreversibly inhibit GABA transaminase partial seizures
levetiracetam unknown partial and tonic clonic
MgSO4 eclamptic seizures (1st line), torsades
triazolam short-acting BDZ increase frequency of Cl channel opening causing anxiety, panic disorder, GAD, detox (esp EtOH withdrawal much larger safety margin than barbiturates, and less respiratory depression; usually
oxazepam propagation of GABAA action; decrease REM and DT), cocaine OD, night terrors, sleepwalking, long t1/2 and active metabolites (short acting BDZs have higher addictive potential);
alprazolam insomnia, general anesthetic, spasticity sedation, tolerance, dependence, CNS depression (additive w/ EtOH); OD: ataxia, minor
respiratory depression; tx=flumazenil (competitive antagonist at GABA-R)
chlordiazepoxide BDZ
lorazepam + acute status epilepticus (first line) or eclamptic seizures
diazepam (after MgSO4)
zolpidem non-BDZ hypnotic act via BZ1 receptor subtype; reversed by flumazenil insomnia short t1/2 (rapidly degraded in liver), so less day-after SFX; ataxia, headaches,
zaleplon confusion; lower dependence risk than BDZ
eszopiclone
halothane unknown; high blood solubility=slower induction and inhaled anesthetic (increase cerebral blood flow, depress hepatotoxicity/necrosis, malignant hyperthermia (all but N2O)
enflurane recovery time; high lipid solubility=high potency=lower CV/resp) proconvulsant
methoxyflurane MAC nephrotoxicity
phencyclidine arylcyclo- (aka PCP) blocks NDMA-R dissociative anesthetic CV stimulant, disorientation, hallucinations, bad dreams, increase cerebral BF
ketamine hexylamine
propofol potentiates GABAA rapid anesthesia induction less post-op nausea than thiopental
succinylcholine motor nACh-R phase I=prolonged depol (no antidote, potentiated by depolarizing paralytic (for pts on a mechanical vent or can cause hyperCa, hyperK, malignant hyperthermia
blocker neostigmine); II=repol but blocked during surgery)
(antidote=neostigmine)
tubocurarine compete for AChRs, reversible w/ cholinesterase non-depolarizing paralytic reversal: AChEI (neostigmine, edrophonium)
pancuronium inhibitors
dantrolene prevents release of Ca from sarcoplasmic reticulum of malignant hyperthermia and neuroleptic malignant
skeletal mm (uncoupled) syndrome, mm relaxant
bromocriptine DA ag (ergot derivative) Parkinson , PRLoma, neuroleptic malignant sz
pramipexole DA ag (non-ergot derivative, so preferred) Parkinson
ropinirole
amantidine increases DA release Parkinson; influenza A, rubella can cause ataxia
levodopa/carbidopa converted to DA in CNS; carbidopa= peripheral dopa- Parkinson (ODISIA) arrhythmias from peripheral conversion to DA; long term can cause dyskinesia
decarboxylase inhibitor following dose, akinesia between doses
ente-/tol-capone COMTI
benztropine antimuscarinic (atropine) Parkinson (tremor and rigidity, not bradykinesia)
reserpine inhibits DA, NE, and 5HT into vescicles (amine Huntington (also haloperidol to tx) Parkinson-like sz
depleting)
tetrabenazine amine depleting (DA)
memantine NMDA-R ant (prevent excitotoxicity) Alzheimer's ("GRiM Dz") dizziness, confusion, hallucinations
rivastigmine AChEI N/V, dizziness, insomnia
donepezil
galantamine
sumatriptan 5HT1B, 1D ag causes vasoconstriction, inhibits V Migrane, cluster headache; short t1/2 (<2h) coronary vasospasm (don't use in pts with CAD or Prinzmetals angina), mild tingling
activation and VIP release
Psych
Drug Class Mechanism Use SFX/other
thioridazine antipsychotic block D2R, but can also block muscarinic, α, and schizophrenia (mostly positive sx), psychosis, mania atropine-like: dry, constipation, hypotn, sedation; corneal (chlorprom-) or retinal
(typical, histamine receptors, all low potency; highly lipid (acute), Tourette's (esp haloperidol) (thiorid-) deposits; both: neuroleptic malignant sz: autonomic instability,
neuroleptic) soluble (long t1/2) myoglobinuria, rigidity, hyperpyrexia, encephalopathy
chlorpromazine
trifluoperazine block D2R, high potency; highly lipid soluble (long t1/2) extrapyramidal (4h=dystonia [mm spasm]; 4d=akinesia [parkinsonian]; 4wk=akathisia
fluphenazine [restlessness]; 4mo=tardive dyskinesia [irreversible stereotypic oral-facial movements
haloperidol + Huntington from long-term use]), hyperPRL
quetiapine atypical block 5-HT2, DA, α, and H1 receptors schizophrenia (positive and negative sx) far fewer extrapyramidal and anticholinergic SFx than neuroleptics
reisperidone antipsycotics
aripiprazole
ziprasidone
clozapine wt gain, agranulocytosis (requires weekly WBC monitor)
olanzapine + OCD, anxiety, depression, mania, Tourette's wt gain
lithium mood stabilizer unknown (maybe inhibits PI3 cascade), ADH bipolar, blocks relapse and acute manic events; SIADH teratogen (atrialized RV [Ebstein's anomaly, malformation of great vessels]),
antagonist; exclusively excreted by kidneys, most hypothyroid, nephrogenic DI, sedation, edema, heart block, tremor; narrow
reabsorbed at PCT with Na therapeutic window
buspirone 5HT1A agonist GAD, anxiety no sedation, addiction, tolerance, EtOH interaction (BDZ/barbiturates)
amitriptyline tricyclic anti- SNRI-like mechanism; amitriptyline=3° (most major depression, fibromyalgia, panic disorder sedation (least=desipramine), convulsions (most=desipramine), α-blocking and
notriptyline depressants anticholinergic); notriptyline=2° (least anticholinergic) anticholinergic (tachycardia, arrhythmias, urinary retention, confusion, hallucinations;
desipramine 3°>>>2°), hyperpyrexia; tx OD w/ NaHCO3 (alkalinize urine)
imipramine + bedwetting (decreases stage 4 sleep)
clomipramine + OCD
(par/flu)-oxetine SSRI usually takes 2-4 weeks for antidepressant effects OCD, social phobia, specific phobia, panic disorder, PTSD, less than TCAs: GI distress, sexual dysfunction, "Seratonin sz" (drug interactions, too
sertraline GAD, anorexia/bulimia, anxiety, depression (typical or much 5-HT causes HyperThermia, HyperTonism, CV collapse, flushing, diarrhea,
citalopram atypical) seizures; tx=cyprohepadine [5HT2 ant])
venlafaxine SNRI 5-HT>NE reuptake inhibitor depression, GAD stimulant effects (htn most common), sedation, nausea
 SNRI stimulant effects (htn most common), sedation, nausea
duloxetine 5-HT<NE reuptake inhibitor depression, diabetic peripheral neuropathy
atomoxitene 5-HT and NE reuptake inhibitor, nonstimulant ADHD
phenelzine MAOI nonselective MAOI, increase NE, 5HT, DA atypical depression, anxiety, hyperchondriasis htnsive crisis (w/ tyramine ingestion and β-ag), CNS stimulation, contraindicated w/
tranylcypromine SSRIs or meperidine (prevent seratonin sz)
isocarboxazid
selegiline selective MAO-BI (main metabolyzer of DA) + Parkinson (use w/ L-dopa) + may enhance SFX from levodopa
varenicline nAChR partial agonist smoking cessation abnormal dreams, change in taste, flatulence/constipation, suicide
bupropion atypical anti- increased NE and DA bipolar, depression, smoking cessation stimulant effects (tachycardia, insomnia), headache, seizure in bulimia
mirtazapine depressants 5HT2&3 and α2-blocker (increased NE and DA) bipolar, depression + insomnia sedation, increased appetite, dry mouth, increased serum cholesterol
maprotiline blocks NE reuptake bipolar, depression sedation, orthostatic hypotension
trazodone blocks 5HT reuptake insomnia, depression (very high doses) sedation, nausea, priapism, postural hypotension
methylphenidate CNS stimulant release stored catecholamines narcolepsy, obesity, ADHD OD: pupil dilation, prolonged wakefulness, delusions, hallucinations, fever; withdrawal:
amphetamine stomach cramps, hunger, hypersomnolent
dexedrine amphetamine ADHD
Addiction
Drug/Type Withdrawal Intoxication
Depressants anxiety, tremor, seizures, insomnia mood elevation, decreased anxiety, sedation, behavioral disinhibition, respiratory depression
acute EtOH severe: DT (life threatening, peaks 2-5d after last drink, ANS hyperactivity emotional lability, ataxia, coma, serum GGT (sensitive EtOH use), AST>2*ALT; acute EtOH=P450 down; chronic EtOH=P450 up, gynecomastia; assn
chronic EtOH [tachycardia, seizures], psychosis, confusion) w/ periventricular hemorrhage/necrosis of mammillary bodies
Stimulants crash, depression, lethargy, wt gain, headache mood elevation, psychomotor agitation, insomnia, arrhythmias, tachycardia, anxiety
caffeine restlessness, diuresis, muscle twitching
nicotine irritability, anxiety, craving restlessness teratogen (preterm labor, placental problems, IUGR, ADHD)
Hallucinogens
PCP depression, anxiety, irritability, restlessness, anergia, thought/sleep homocidality, delerium, belligerence, fever, nystagmus, tachycardia, psychomotor agitation, impulsiveness
disturbances
LSD flashbacks, pupillary dilation, marked anxiety/depression, delusions, visual hallucinations
marijuana irritability, depression, insomnia, N, anorexia; peak in 48h, last up to 7days; paranoid delusions, slowed time perception, social withdrawal, dry mouth, hallucinations
can be detected in urine for up to 1 month
Renal
Drug Class Mechanism Use SFX/other
mannitol osmotic diuretic shock, drug OD, increased ICP/IOP pulmonary edema, dehydration, contraindicated in anuria and CHF
acetazolamide carbonic anhydrase inhibitor urinary alk (TCA/bartbiturate/salicylate OD, cystinuria), hyperchloremic (nAG) MAc, neuropathy, NH3 toxicity, sulfa
MAlk, altitude sickness, glaucoma
ethacrynic acid loop diuretic phenoxyacetate derivative, same as Lasix diuresis in sulfa-allergies or gout pts ototoxicity, hypokalemia, dehydration, interstitial nephritis
furosemide inhibit cotransport of NaK2Cl; lose hyper-tonicity of edema (CHF, cirrhosis, nephrotic sz, pulmonary edema), + sulfa allergy and gout
medulla, increase Ca excretion htn, hypercalcemia
hydrochlorothiazide thiazide inhibit NaCl reabs in distal tubule, low Ca excretion htn, CHF, idiopathic hypercalciuria, nephrogenic DI hypokalemic MAlk, hyponatremia (low big 3), hyperglycemia, hyperlipidemia,
hyperuricemia (gout), hypercalcemia, sulfa allergy
eplerenone K-sparing diuretics competitive aldoR ant hyperaldo, K-depletion, CHF, hirsutism (spironolactone) hyperkalemia, MAc
spironolactone + mild testosterone R ant endocrine SFx (antiandrogen, gynecomastia, amenorrhea)
triamterine block ENaC in DCT hyperkalemia, MAc
amiloride + nephrogenic DI
captopril ACEI inhibit inactivation of bradykinin (vasodilator); causes htn, CHF, diabetic renal dz cough (not ARBs), angioedema (lip/larynx edema), teratogen (renal damage),
lisinopril renin release by loss of feedback inhibition proteinuria, taste change, hypotn, hyperK; NOT in bilateral renal a stenosis (decrease
enalapril GFR by preventing efferent constriction)
Repro
Drug Class Mechanism Use SFX/other
leuprolide GnRH ag pulsatile=agonist, continuous=antagonist infertility, prostate ca (+ flutamide), fibroids antiandrogen, N/V
methyltestosterone T agonist at androgen receptors hypogonadism, develop 2° sex characteristics, burn pts masculinization in females, reduces intratesticular testosterone in males (inhibits LH)
(promotes anabolism) causing gonadal atrophy, premature closure of epiphyseal plates, raise LDL, lower HDL

finasteride 5α-reductase inhibitor, lower DHT BPH, male pattern baldness gynecomastia
flutamide nonsteroidal competitive T-receptor ant prostate cancer (+ leuprolide)
ethinyl estradiol estrogen Estrogen receptor antagonist hypogonadism, POF, menstrual abnormailities, endometrial cancer, postmenopausal bleeding, VTE; contraindications: ER-positive
postmenopausal HRT, androgen-dependent prostate breast cancer, hx of DVTs
cancer
 estrogen Estrogen receptor antagonist hypogonadism, POF, menstrual abnormailities, endometrial cancer, postmenopausal bleeding, VTE; contraindications: ER-positive
mestranol postmenopausal HRT, androgen-dependent prostate breast cancer, hx of DVTs
diethylstilbestrol cancer teratogen (vaginal clear cell adenoC)
clomiphene SERM inhibits negative feedback on hypthalamus ovulation induction hot flashes, ovarian enlargement, multiple pregnancies, visual disturbances
tamoxifen ag: bone, endometrium; antag: breast breast cancer (ER-positive), prevent osteoporosis endometrial carcinoma, hot flashes
raloxifene ag: bone; antag: endometrium, breast
HRT menopausal sx (hot flashes, vaginal atrophy, osteoporosis unopposed estrogen RT increases the risk of endometrial cancer (P added), possible
[E2 decreases osteoclast activity]) increased CV risk
exemestane aromatase inhibitor ER-positive breast cancer in postmenopausal women masculinization, premature epiphysial plate closure
anastrozole
progestin reduce growth and vascularization of endometrium oral contraceptives, endometrial cancer, abnormal uterine
bleeding
mifepristone (RU-486) competitive progesterone inhibitor pregnancy termination (+ misoprostol) heavy bleeding, N/V, anorexia, abdominal pain
dinoprostone PGE2 analog (dilation, uterine contraction) labor inducer
terbutaline Symp ag β2 reduce premature uterine contractions
ritodrine
tamsulosin α1A,DR ant (on prostate, α1BR on vessels) BPH (inhibits only prostatic smooth m)
sildenafil inhibit cGMP PDE5I ED headache, flushing, dyspepsia, impaired blue-green color vision, life-threatening
vardenafil hypotn in pts taking nitrates
Respiratory
Drug Class Mechanism Use SFX/other
diphenhydramine 1G H1 blockers reversible inhibitors of H1 histamine R allergy, motion sickness, sleep aid sedation, antimuscarinic, anti-α-adrenergic
chlorpheniramine
loratadine 2G H1 blockers allergy less entry to CNS than 1G, so far less sedation
fexofenadine
desloratadine
certirizine
methacholine direct ACh ag inhaled, causes bronchoconstriction challenge test for dx of asthma anti-DUMBBELSS
ipratropium ACh ant competitive block of MACh-R asthma, COPD
isoproterenol Symp ag β lowers BP (not used), asthma tachycardia
metaproterenol Symp ag selective β2 ag (β2>>β1) acute asthma
albuterol acute asthma
salmeterol long term asthma (attack prophylaxis) tremor, arrhythmia
theophylline methylxanthine PDEI (decreases cAMP hydrolysis) asthma, adenosine toxicity narrow TI (OD=β-blocker), cardio-/neuro-toxic, metabolized by P450
cromolyn stabilizes mast cell granules only for asthma/allergy prophylaxis, not tx
zileuton antiLT 5-lipoxygenase inhibitor (AA to LTs) asthma
(zafir)-lukast LT receptor antagonist asthma (especially aspirin-induced)
guaifenesin expectorant does not suppress cough reflex
N-acetylcysteine mucolytic, glutathione precursor loosen plugs (CF), acetaminophen OD
bosentan endothelin-1 receptor antagonist (lower PVR) pulmonary htn
Biochem
Name Vitamin Function Deficiency Excess
retinol A antioxidant, used in vision pigment, cell differentiation nyctalopia (night blindness), dry skin acute: N/V/dizziness, blurred vision; chronic: hepatotoxicity, increased ICP,
(tx AML M3), also used to treat measles papilledema, arthralgias, fatigue, headaches, skin changes, sore throat, alopecia;
teratogenic (cardiac abnormalities, cleft palate)
calcitriol (D3) D increase intestinal absorption of Ca and PO4 rickets (kids), osteomalacia, hypocalcemic tetany, breast hypercalcemia (delerium, stupor, stones), loss of appetite; seen in sarcoid: activated
milk is low in vitamin D macrophages pump out vit D
vitamin E E antioxidant (RBCs and cell membranes) hemolytic anemia, mm weakness, posterior column and
spinocerebellar demyelination
vitamin K K catalyzes γ-carboxylation of glutamate on clotting neonatal hemorrhage w/ increased PT and PTT, normal
factors (II, VII, IX, X, protein C, S) bleeding time; warfarin, cephalosporin
thimine B1 cofactor for PDH, α-KGDH, transketolase (HMP shunt), Wernicke-Korsakoff or Beriberi (wet=dry + high output
branched chain AA DH cardiac failure; dry=polyneuritis, symmetrical mm
wasting); glucose can worsen
riboflavin B2 cofactor in redox (FADH2) cheilosis (inflammation of lips), corneal vascularization
niacin B3 made from tryptophan and B6 glossitis; severe=pellagra (diarrhea, dermatitis [Casal's facial flushing (tx of hyperlipidemia), acanthosis nigricans, hyperuricemia
collar], dementia)
pantothenate B5 CoA (acyl transfers and FA synth) dermatitis, enteritis, alopecia, adrenal insuff
pyridoxal P B6 used in a ton of rxns (make niacin from trp); deficiency convulsions, hyperirritability, peripheral neuropathy,
caused by INH, OCPs sideroblastic anemia, pellagra
cobalamin B12 homocysteine methyltransferase (regeneration of megaloblastic anemia, hypersegmented PMNs, neuro sx;
methionine after SAM) and methylmalonyl-CoA from malabsorption in terminal ileum (Crohn's, sprue,
mutase (generation of succinyl CoA from catabolism) enteritis, D. latum) or lack of intrinsic factor (PA, gastric
cofactor bypass)
folate nucleic acid synth, methyl transfers (SAM); most megaloblastic anemia, no neuro sx, but teratogenic
common deficiency in US (alcoholics and pregnancy) (neural tube defects); can be from drugs (phenytoin, MTX,
sulfonamides)
biotin (B7) cofactor for carboxylations (pyruvate, acetyl-CoA, dermatitis, alopecia, enteritis; rare: excessive ingestion of
propionyl CoA) raw eggs (avidin) or abx use
ascorbic acid C antioxidant, facilitates Fe absorption, collagen scurvy: swollen gums, bruising, hemarthrosis, anemia,
synthesis, DA to NE poor wound healing, weak immune
Zn essential for 100+ enzymes, transcription factors (Zn poor wound healing, hypogonadism, decreased adult hair,
fingers) dysgeysia, anosmia, risk of cirrhosis
Toxins/Antidotes
drug class antidote SFX/other Mechanism
salicylate NaHCO3 (alkalinize urine), dialysis not for gout (need too high of a dose)
iron (hemochromatosis) deferoxamine acute: gastric bleeding; chronic: MAc, GI scarring peroxidation of membrane lipids
lead 1st line: CaEDTA and dimercaprol, 2nd: penicillamine; succimer for kids
mercury dimercaprol (BAL), succimer
arsenic dimercaprol (BAL), succimer, penicillamine vomiting, rice water stool, garlic breath; SqCC inhibits lipoic acid (pyruvate and α-KG DH complexes)
gold
copper (Wilson's) penicillamine
cyanide nitrite, hydroxocobalamin, thiosulfate can be from nitroprusside (tx for malignant htn) electron transport inhibitor
methemoglobin methylene blue, vitamin C created by nitrite bc it binds CN strongly
CO 100% O2, hyperbaric O2 electron transport inhibitor
methanol ethanol, fomepizole, dialysis inhibit alcohol dehydrogenase
ethylene glycol
benzene aplastic anemia
ouabain inhibits Na/K ATPase (bind K site)
Amanita phalloides (poison hepatotoxicity/necrosis α-amantin inhibits RNA Pol II
mushroom)
antimycin A electron transport inhibitor
rotenone electron transport inhibitor
oligomycin mitochondrial ATPase inhibitor
2,4-DNP uncoupling agent
organophosphates atropine irreversible AChEI (AChE regenerated by atropine)
 Biochem (pathology)
collagen one=90%, bONE, skin, tendon, dentin, fascia, cornea, late wound repair; II=cartilage, vitreus, nucleus pulposis; III (reticulin) XLR diseases (XLD=hypophosphatemic rickets)
=skin, vessels, uterus, fetal tissue, granulation tissue (think Ehlers-Danlos); IV=BM 2 blood dzs G6PDD Hemophilia (A and B)
Kwashiorkor: protein malnutrition (lesions, belly); marasmus: energy malnutrition (wasting) 2 binomial dzs Lesch-Nyhan Wiskott-Aldrich
essential fructosuria: AR fructokinase def, fructose doesn't enter cells, asxatic except for fructosuria 2 B's Becker's MD (+DMD) Bruton's agammaglobulinemia
fructose intolerance: AR aldolase B deficiency, F1P accumulation, depletion of P, inhibition of glycogenolysis, gluconeogenesis; sx: 2 O's Ocular albinism OTC deficiency
hypoglycemia, jaundice, cirrhosis, V; tx: no fructose/sucrose intake 2 LSDs Fabry's Hunter's
galactokinase deficiency: AR, relatively mild, accumulation of galactitol (infantile cataracts), galactosuria
classic galactosemia: AR gal-1-P UT def; sx: infantile cataracts, FTT, jaundice, HM, retardation; tx: no lactose Amino acids (GluM HArV, PITT)
alkaptonuria (ochronosis): AR homogentisic acid oxidase def, degrades Tyr to fumarate; sx: mostly benign, urine turns black on Essential Ketogenic Leucine, Lysine
standing, dark connective tissue/sclera, older get arthralgias (HGA toxic to cartilige) Glucogenic Methionine, Valine, Arginine, Histidine
MSUD: α-ketoacid DH def, no degradation of branched AAs (Ile, Val, Leu); organic acidemia, sweet odor Both Phenylalanine, Isoleucine, Threonine, Tryptophan
Acidic Glutamate, Aspartate
Basic Lysine, Arginine (most basic), Histidine (no charge at body pH)
homocystinuria (HCU): excess HC, C becomes essential, 3 forms (cystathione synthase deficiency [tx=high B12/folate/diet=hi cys low
met], low affinity of cystathione synthase for B6 [tx=high B6], HC methyltransferase deficiency); sx: HCU, mental retardation,
osteoporosis, kyphosis, marfanoid habitus, inferonasal sublux of lens, atherosclerosis (stroke, MI);; cystinuria: defect of renal tubular Lipid transport
positive-AA transporter (cysteine, ornithine, lysine, arginine); sx: cystine kidney stones (staghorn); tx: acetazolamide (alkalinize urine) Particle Chylomicron VLDL IDL LDL HDL
fraGile X: 2nd most common cause of M retardation; (CGG) repeat, methylation and underexpression of FMR1, macroochidism, long Proteins B-48, C-2, E B-100, C-2, E B-100, E B-100 A-1, A-2
face, large jaw, big ears, MVP; karyotype in folate def medium=discontinuous staining LCAT: lecithin-chlsl acyltransferase, in HDL and LDL, esterifies 2/3 of plasma chlsl
ionizing radiation causes dsDNA breaks, end-joining enzyme repair (no sequence homology necessary) CETP: chlslester transfer protein, takes chlsl from HDL to LDL/VLDL, TG back to HDL
deamination causes abnormal bases, glycosylation makes AP site, AP endonuclease, DNA Pol, and ligase fix hyperchylomicronemia (I): LPL def or altered apoC-II (cofactor) causes high TG and chlsl;
UV makes T-T, UV-specific endonucleases cause site specific strand break, exonuclease removal, Pol/ligase fix (def=XP); DNA Pol III pancreatitis, HSM, eruptive xanthomas, no increased risk for atherosclerosis
has 3'-5' exonuclease proofreading activity for mismatch repair (def=HNPCC) familial hyperchlslemia (IIa): AD, absent LDL-R causes increased LDL, chlsl, tendon (Achilles)
biotin for carboxylation rxns (pyruvate to OAA, [AAs to] propionyl CoA to succinyl CoA); def=organic aciduria xanthomas, accelerated atherosclerosis (MI<20yo), corneal arcus
αKG/P/αKADH cofactors: B1, 2, 3, 5, lipoate (LA inhibited by arsenic [vomiting, rice water stool, garlic breath]) hyperTGemia (IV): hepatic VLDL overproduction causes increased TG, pancreatitis
PDH def: lactic MAc, neuro sx, hemolytic anemia; can be congenital or acquired (B1 def); tx=fatty/lys/leu diet abetalipoproteinemia: AR, MTP (microsomal TAG transfer protein, loads apoB with lipids) def causes
CF: AR CFTR (7) mutation (commonly Phe 508, abnormal folding, degradation), normally secretes Cl in lungs and GI, resorbs in sweat inabilty to synthesize VLDL/chylo; sx: FTT, ataxia, steatorrhea, malabsorption, nyctalopia,
glands (high Cl in sweat=dxtic); infertility in M (bilateral agenesis of vas), mucus plugs in liver, panc, & lungs (Pseudomonas/S. aureus, acanthocytosis, intestinal biopsy full of lipid
chronic bronchitis, bronchiectasis, panc insufficiency, ADEK malabs, FTT, steatorrhea, meconium in newborns); tx=N-acetylcysteine
(breaks glycoprotein S-S bonds)
PKU: Phe OHase or THB def, Tyr is essential, screened for 2-3d after birth (normal at birth from
OTC def: XLR, most common urea cycle disorder (others AR), usually early onset (can be late), xs carbamoyl-P to orotate; sx: orotic maternal enzyme); sx: mental/growth retardation, seizures, musty body odor, fair skin, eczema;
aciduria, low BUN, hyperNH3 (cerebral edema, blurry vision, tremor, V, speech slurring) maternal PKU: microcephaly, mental/growth retardation, CHD
carnitine def: inability to transport LCFAs into mitochondria; sx: hypoketotic hypoglycemia, hypotonia, weak branched/VLCFA cant undergo β-ox, so degraded in peroxisomes (def causes improper CNS
acyl-CoA DH def: hypoketotic hypoglycemia with dicarboxylic acid-emia/-uria (substrate of deficient enzyme) myelination)

Embryo
embryonic craniocaudal segmentation caused by homeobox gene, AP-patterning from sonic hedgehog (from ZPA) and Wnt-7 (from Fetal landmarks
AER), limb lengthening induced by FGF (from AER, stimulates mesoderm mitosis) wk1 d3=morula; d6=blastocyst implantation, hCG secretion begins
notochord induces overlying ectoderm to neural plate; neural plate becomes neural tube and neural crest cells; notochord becomes wk2 bilaminar disk (epi-/hypo-blast), placenta (syncytio-/cyto-trophoblast)
nucleus pulposis of intervertebral disks; cardinal vv become SVC wk3 gastrulation/primitive streak; d18=notochord; d21=neural tube closure
allantois: contains umbilical aa & vv, urachus (bladder-yolk sac), vitelline duct (midgut-yolk sac, "yolk stalk") wk4 heartbeat, limb buds form (4 chambers, 4 limbs)
erythropoiesis wk3-8=yolk sac (Gower Hb=ζ2ε2); wk6-30=liver and spleen (9-28, HbF); wk28+=bone marrow wks3-8 embryonic period: organogenesis, most susceptible to teratogens
indomethacin helps close PDA, PGs (decrease with increase in O2) keep PDA open (PDA=continuous murmur) wk8 fetal period: movement, looks like baby
neural tube defect: high AFP; anencephaly: high AFP, polyhydramnios (no swallowing center) wk10 genitalia have M/F characteristics
branchial apparatus cleft=ectoderm (1=external auditory meatus; 2-4 form temporary cervical sinuses, can form cysts),
arch=mesoderm, pouch=endoderm (1=ear, 2=tonsils, 3=thymus, 3/4=inf/superior parathyroid) Embryologic derivatives
failure of fusion cleft lip=maxillary, medial nasal; palate=lateral palatines, medial palatine, nasal septum surface epidermis, adenohypophysis, lens, salivary/sweat/mammilary glands, oral/olfactory
wk6: midgut herniates through umbilical ring, returns and rotates around SMA wk10; gastroschisis=extrusion of GI contents through ectoderm epithelium, sensory organs of inner ear
folds, not covered by peritoneum; omphalocele=into umbilical cord, peritoneal cover neuro- CNS (brain, neurohypophysis, oligodendrocytes, astrocytes, ependymal cells, spinal
pancreas: dorsal and ventral buds contribute to head, main duct; rest is only dorsal; fusion at wk8 ectoderm cord), retina
metanephros appears wk5, ureteric bud from caudal end of mesonephros forms ureter, pelvices, calyces, collecting ducts, and PNS (incl. chromaffin cells of adrenal medulla), AP septum, pia, arachnoid, skull
induces metanephric mesenchyme differentiation (glomeruli to DCT); ureteropelvic jctn=last site to canalize, most common site of neural crest bones, odontoblasts, C-cells of thyroid, melanocytes
obstruction causing fetal hydronephrosis Vertebral, Anal atresia, Cardiac, Tracheo-Esophageal fistula, Renal, Limb; bone, mm,
internal genitalia F=paramesonephric (Mullerian) duct, will fuse; M=mesonephric (Wolffian) duct; external: tubercle=penis or meso-derm connective tissue/dura, spleen, GU, Eustachian tube
clit/bulbs, UG sinus forms glands (including prostate), labioscrotal swelling forms covers
gubernaculum: F=ovarian/round lig, M=anchors testis; processus vaginalis becomes tunica in M (nothing in F) endo-derm gut tube epithelium and derivatives (lungs, liver, panc, thymus, parathyroid)
Down Sz: duodenal atresia, ASD, VSD, AVSD (endocardial cushion defect), Hirschsprung dz, AML, ALL; low AFP and estriol, high β-hCG and inhibin A, increased nuchal translucency; 95% from meiotic nondisjunction
 Micro
TNF/IL-1 inducers: teichoic acid (GP) and lipid A (GN); major Ag: peptidoglycan (GP) and LPS (GN) Bacteria
GPR: "BaCCiLuM"=Bacillus, Corynebacterium, Clostridium, Listeria, Mycobacteria (mycolic acid in cell wall) pus, empyema, abscess S. aureus
intracellular obligate=Rickettsia, Chlamydia; facultative=Legionella, Neisseria, Mycobacteria (bird), Brucella (cow), Listeria (cow), asplenic/Sickle cell Capsule, esp S. pneumo, H. flu, N. meningitides
Francisella (rabbit), Yersinia (prairie dog), Salmonella (reptiles) pneumonia in CF, burn infxn Pseudomonas aeruginosa
capsule (polysaccharide): S. pneumo, H. flu, N. meningitides, K. pneumo, Salmonella, B. anthracis (D-glu) traumatic open wound C. perfringes (gas gangrene)
virulence factors Protein A (S. aureus, binds Ig Fc), IgA protease (S. pneumo, H. flu, N. meningitides), M protein (S. pyogenes, surgical wound S. aureus
prevents phagocytosis); E. coli: fimbriae (pyelo/cystitis), H=flagella, K=capsule (meningitis, pneu-monia), O=LPS; paramyxovirus: F- dog/cat bite Pasteurella multocida
protein (causes respiratory epithelial cells to fuse to multinucleated cells) currant jelly sputum Klebsiella
PAS Trophyerma whippelii
exotoxins ADP-ribosylating: B=binding, A=active (enzymatic); C. diphtheriae/Pseudomonas exotoxin: inactivates EF-2; V. cholerae
meningitis/sepsis in newborn S. agalactiae (group B)
(activates Gs), B. pertussis (inactivates Gi), E. coli heat labile toxin (directly) all stimulate adenylate cyclase (B. anthracis toxin
["edema factor"] is an adenylate cyclase); other exotoxins: C. perfringes (α toxin=lecithinase), C. tetani (inhibits GABA and glycine), C. health care provider HBV (needle stick)
botulinum (inhibits ACh release), S. pyogenes (streptolysin O, erythrogenic), Shigella/E. coli O157:H7 (cleaves 60S rRNA) [bold coded fungal infxn in DM Mucor/Rhizopus
on phages] chronic granulomatous dz catalase (+): S. aureus, Nocardia, Aspergillus
endotoxin macrophages [IL-1 (fever), TNF (fever, hemorrhagic tissue necrosis), NO (hypotn)]; XII (coagulation cascade and DIC); neutropenic patients Candida (systemic), Aspergillus
alternate complement pathway [C3 (hypotn, edema), C5 (chemotaxis), both anaphylactic] bilateral Bell's palsy Borrelia burgorferi (Ixodes, so is Erlichia & Babesia)
S. pyogenes: rheumatic fever=subQ nodules, migratory polyarthritis, erythema marginatum, chorea, carditis stroke w/o htn syphilis
VDRL: Ab to beef cardiolipin, false positives=viral (EBV, hepatitis), drugs, rheumatic fever, lupus, leprosy pediatric infxn (incl. epiglotitis) H. flu
Weil-Felix rxn: anti-Rickettsia Abs (not Q-fever) agglutinate w/ Proteus O Ags; monospot=sheep RBCs oral infxn, branching rods, sulfur granules Actinomyces israelii
C. trachomatis serotypes: A-C=African follicular conjunctivits; L1-L3=lymphogranuloma venereum (ulcers, rectal stricture, LAD); D-
K=urethritis, subacute PID, ectopic, neonatal pneumonia/conjunctivitis Parasites
brain cysts, seizures Taenia solium (cysticercosis) mebendazole
histo: in macrophages; blasto: broad-based buds; coccidioidomycosis: spherule (not yeast) in tissue; Candida: yeast w/
pseudohyphae, germ tube at 37; M. furfur: "spaghetti and meatballs"; dermatophytes: mold hyphae on KOH; Aspergillus: invasive in liver cysts Echinococcus granulosus albendazole
chronic granulomatous dz, acute-branching septate hyphae; C. neoformans: heavy capsule, yeast, narrow-based buds; B12 def Diphyllobothrum latum raw fish
Mucor/Rhizopus: irregular, non-septate hyphae, frontal lobe in DM biliary tract dz, cholangioca Clonorchis sinensis raw fish
Plasmodia schizont to hepatocyte to merozoite to RBC to trophozoite, gametocyte to mosquito; headache, anemia, splenomegaly; hematuria, SqC bladder cancer Schistosoma hematobium inflamed spleen/ liver,
malariae: 72hr cyclic fever; vivax/ovale: 48hr cycle, dormant hypnozoite in liver (tx=primaquine); falciparum: daily fever, RBC occlude portal htn Schistosoma mansoni granulomas
capillaries (brain, kidney, lung); Babesia: maltese cross hemoptysis Paragonimus westermani from bacterial infxn
vax live (no booster)=VZV, Sabins polio, MMR, smallpox, yellow fever; killed (only humoral immunity)=Salks polio, Rabies, flu, HAV; microcytic anemia Ancyclostoma, Necator hookworms
recombinant=HPV, HBV; H. flu=conjugated capsular polysaccharide/diphtheria toxoid perianal pruritis Enterobius (pinworms) nematode
non-infxous genomes dsRNA (reo-) and (-) ssRNA (Always Bring Polymerase Or Fail Replication: Arena, Bunya, Paramyxo, Orthomyxo, periorbital edema/m inflamed Trichinella spiralis raw pork
Flavi, Rhabdo); segmented: Arena (2), Bunya (3), Orthomyxo (8), Reo (10) hyperpigmentation, blindness Onchocerca volvulus microfilaria allergy
exceptions RNA: nuclear replication=orthomyxo and retro, non-encapsulated=enterovirus: calici (norwalk), reo (rota), hepe (HEV), Protozoa
picorna (HAV); DNA: encapsulated=hepadna (think of HCV/HDV, circular), herpes, pox horseshoe-crab shaped Giardia or Trichomonas steatorrhea/STD
HepB HBe is in the core, indicates viral replication, high transmissibility; anti-HBe=low transmissibility; test: incubation pd (infxn- liver abscess Entamoeba dysentery
mo2)=HBs; prodrome/acute (mo2-5)=HBs or anti-HBc; convalescent: early (equivalence/ window period, mo5-6.5)=anti-HBc, fever, HSM, pancytopenia Leishmania amastigotes too
late=anti-HBs; HBe has a window period 1-2mo before HBs; vax=anti-HBs
HIV: env=gp120 (attachment to TC) and gp41 (fusion); pol=RTase; gag=p24 (capsid protein); CCR5 and CXCR4 Pneumonia
osteomyelitis: usually in children, bone pain and elevated APRs (CRP, ESR), S. aureus usually; can be N. gonorrhea (usually from neonates children adults elderly
septic arthritis), P. aeruginosa (DM/IVDU), Salmonella (sickle cell), Pasteurella (bite) S. agalactiae S. pneumo S. pneumo S. pneumo
UTI: dysuria, frequency, urgency, suprapubic pain, WBCs, no casts; leukocyte esterase=bacterial, NO2-=GN; E. coli, S. saprophyticus, E. coli RSV/other viruses C. pneumo viruses (flu)
K. pneumo; nosocomial: Serratia, Enterobacter, Pseudomonas; Proteus=struvite stones C. pneumo M. pneumo anaerobes
M. pneumo H. flu H. flu
ToRCHeS jaundice, HSN, thrombocytopenia, growth retardation; Toxo: chorioretinitis, hydrocephalus, and intracranial calcifications;
Rubella: (PDA/pulmonary a stenosis, septal def), cataracts, deafness ± blueberry muffin rash; CMV: hearing loss, seizures, petechial anaerobes/viruses GNR
rash; HIV: recurrent infxn/diarrhea; HSV: temporal enceph-alitis; Syphilis: hydrops, facial abnormalities (saber shins, Hutchinson's
teeth, saddle nose), CN VIII deafness Meningitis
superficial vascular proliferation in HIV lymphocytes=Kaposi's, PMNs=bacillary angiomatosis, from Bartonella neonates children adults elderly
S. agalactiae S. pneumo S. pneumo S. pneumo
Bug (special medium): B. pertussis (Bordet-Gengou agar), M. TB (Lowenstein-Jensen agar), H. flu (chocolate agar, V [NAD] and X
E. coli enteroviruses enteroviruses GNR
[hematin]), M. pneumo (Eaton's agar), N. gonorrhea (Thayer-Martin/VPN), C. diphtheriae (Tellurite agar, Loffler's media), E. coli
(EMB), yeast (Sabouraud's agar), Legionella (charcoal yeast extract, cysteine, Fe); Bugs (special stain): Trophyerma whippelii (PAS), C. L. monocytogenes N. meningitides N. meningitides L. monocytogenes
neoformans (mucicaramine or India ink), Legionella/fungi (silver), acid fast (Ziehl-Neelsen), H. flu (unvax'ed) HSV
Borrelia/chlamydia/Plasmodium/trypanosomes (Giemsa) meningism (nuchal rigidity, photophobia, headache), Kernig's sign (flex hip, rigidity on knee
bacterioSTaTEC: SMX, Trimethoprim, Tetracyclines, Erythromycin, Clindamycin, Chloramphenicol extension), Brudzinski's sign (prone, head lifted, feet lift involuntarily)
non-dimorphic fungi mold: Aspergillus (acute angles), dermatophytes; yeast: C. neoformans (capsule), PCP
Candida=germ tubes @ 37°C; mucor/rhizopus=nonseptate; coccidioides=spherule; histoplasma=intracellular
ability to take environmental DNA=competence, SHiN; transduction=w/ viruses, lysogenic=specialized (toxins)
adenovirus: conjunctivitis, cystitis, febrile pharyngitis, pneumonia, intussusception (in young, older=mass)
Immune
HLA/disease associations
LNs paracortex: high-endothelial venules; cortex: BC; medulla: cords (lymphocytes, plasma cells), sinuses (macrophages); Spleen red A3 Hemochromatosis DR3 DM type I
pulp: RBC; marginal zone: APCs; white pulp: follicles (BCs) and PALS (TCs); lymph drainage: above pectinate line to internal iliacs, B8 Graves' Dz DR4 RA, DM type I
below pectinate line/superficial thigh/scrotum to superficial inguinals, testes to superficial and deep plexuses to paraaortic B27 Sero(-) spondyloarthropathies DR5 pernicious anemia, Hashimoto's
TC maturation precursor from bone marrow to thymus; CD4+CD8+TC in cortex, (positive selection), CMJ, into pale medulla (negative DR2 hay fever, anti-GBM, SLE, MS DR7 steroid-responisve nephrotic sz
selection, Hassall's corpuscles, epithelial reticular cells express AIRE, TC differentiate to CD4 or CD8 lineage); TC activation CD8:
1=MHC1, 2=IL-2; CD4: 1=MHC2 from APC, 2=B7 (sensed by CD28) Cytokines (Mnemonic: "Hot D8, My GoodnEss, A Hot/Cute Lynn Comes")
Th1: induced by IL-12, regulates cell-mediated response, secretes IL-2, -3, and IFN-γ, inhibited by IL-10 IL-1 MP pyrogen, induces endothelial adhesion molecules/chemokines
Th2: induced by IL-4, regulates humoral response, secretes IL-3, -4, -5, -6, -10, inhibited by IFN-γ IL-2 Th1 activates CD8 (signal 2)
BC: 1=IL from Th2, 2=CD40L; IL-4=IgG (crosses placenta) and IgE; IL-5=IgA (breast milk, mono-/di-mer); -6 & -10 IL-3 TCs hematopoietic cells to become myeloid precursors
complement C1-4=viral neutralization, C3b=opsonize, C3a or C5a=anaphylaxis, C5a=chemotaxis; deficiencies: autoimmune IL-4 Th2 differentiation to Th2, and class switching to IgG and IgE
protectors=C1 esterase (hereditary angioedema) and decay accelerating factor/GPI (PNH); C3=severe recurrent pyogenic sinus/RTI, IL-5 Th2 differentiation of BC, class switch to IgA, eosinophil maturation
increased type III hypersensitivity; C5-8=Neisseria bacteremia IL-6 MP/Th2 pyrogen, induces acute phase reactants
cell surface proteins TC: TCR, CD3 (signal transduction, OKT-3 blocks), CD28 (signal 2), CD40L (only Th2), CXCR4 (HIV); BC: CD19 (on all IL-7 lots hematopoietic cells to become lymphoid precursors
BC lymphomas), CD20 (rituximab), CD21 (EBV), CD40 (signal 2), B7; macrophages: B7, CD40, CD14 (endotoxin-R), FcR, C3bR, CCR5 IL-8 MP chemotactic
(HIV, mutation=immunity); NK: CD56 (marker), CD16 (IgG Fc) IL-9 Th2 acts on hematopoietic cells, anti-apoptotic, pro-growth
preformed Abs given after exposure to rabies, tetanus, HBV, botulinum toxin IL-10 Th2, Treg activates Th2, inhibits activated TC and Th1
Bruton's agammaglobulinemia: BTK defect (tyrosine kinase) blocks pre-BC to immature BC, normal pro-B IL-11 ? hematopoietic cells to become megakaryocytes, bone prolif
Hyper-IgM: defective CD40L on Th2, inability to class switch, causes severe pyogenic infxns early IL-12 MP, BC differentiation to Th1, activates NK
selective Ig def: IgA most common, sinus/lung infxn, milk allergy, anaphylaxis w/ transfusion TNF-α MP mediates septic shock, activates endothelium, leaky
common variable ID: BC maturation def, acquired in 20s, assn w/ autoimmune dzs, lymphoma, low Ig/plasmas IFN-γ Th1 activates macrophages and Th1, inhibits Th2, ups MHC1 and 2
IL-12R def: Th1 def, low IFN-γ, causes disseminated mycobacterial infxn
hyper-IgE (Job's Sz): no IFN-γ causes no neutrophil response to chemotactic stimuli; sx: coarse facies, "cold" abscesses, retained AutoAbs and associated disorder
primary teeth, hyper-IgE, derm problems (eczema, eg) anti- dz anti- dz
SCID: can be IL-2R def (most common, XL), adenosine deaminase def, MHC2 mutations; tx=marrow transplant histone drug-induced lupus glu decarboxylase DM type 1
ataxia-telangiectasia: DNA repair (ds breaks) def causes cerebellar defects, IgA def, and spider angiomas IgG RA gliadin/endomysial Celiac
Wiskott-Aldrich: XLR, deletion of B and TC; thrombocytopenic purpura, infxns, eczema; high IgE, IgA, low IgM Scl-70 scleroderma (diffuse) centromere CREST
leukocyte adhesion def: defect in LFA-1 integrin (CD18) on phagocytes (binds ICAM-1 on endothelium and APCs); recurrent bacterial U1-RNP mixed connective tissue microsomal/thyroG Hashimoto's
infxns, no pus formation, delayed separation of the umbilicus, neutrophilia smooth m autoimmune hepatitis mitochondrial PBC
chronic granulomatous dz: NADPH oxidase def causes absent respiratory burst in PMNs, high susceptibility to catalase positive BP-180 bullous pemphigoid desmoglein pemphigus vulgaris
organisms (S. aureus, E. coli, Aspergillus), negative nitroblue tetrazolium dye reduction test Jo-1 polymyositis/dermatomyositis c-ANCA Wegener's

Path
apoptosis intrinsic: up Bax, down Bcl-2 cause increased mitochondrial permeability, cytochrome c release; extrinsic: Fas (CD95)-FasL Amyloid: β-sheet, Congo red stain, apple green birefringence, gross=waxy
or perforin/granzyme (+granulysin in CTC) attack; both cause Ca influx, activating caspases, nuclear basophilia/shrinkage (pyknosis), Primary AL from Ig light chains (multiple myeloma, BJ proteins)
fragmentation (karyorrhexis), fading (karyolysis), blebs Secondary AA serum amyloid-ass'd protein (chronic inflammation)
granulation tissue: vascular, replaces fibrin in wound; granuloma: wall of macrophages, maintained by TNF-α Senile cardiac AF from transthyretin
diapedesis rolling: E-/P-selectins (vessel) bind Sialyl-LewisX (Leukocyte); tight binding: ICAM-1 (v) binds LFA-1 (aka integrin, L); DM type 2 AE from amylin
diapedesis: PECAM-1 (CD31, both); migration: bacterial products, C5a, IL-8, LTB4, Kallekrein thyroid medullary ca A-CAL from calcitonin
free radical injury: common in prematurity (retinopathy, BPD), drugs (Fe, acetaminophen, CCl4), reperfusion Alzheimer's β-amyloid from amyloid precursor protein
ESR: inflammatory products coat RBC, cause aggregates (fall at higher rate); low=sickle cell, polycythemia, CHF dialysis-associated β2-μG from MHC I proteins
tuberous sclerosis: AD, giant cell astrocytoma, angiomyolipoma, cardiac rhabdomyoma, adenoma sebaceum, hamartomas
(CNS=seizures), ash leaf spots, shagreen patch; autoimmune diseases ass'd w/ lymphoma Oncogenes: one mutation needed Tumor suppressors: two mutations needed
tumor markers AFP: HCC, nonseminomatous germ cell tumors of testis; S-100: melanoma, neural tumor (astro); β-hCG: gene tumors (gene product) gene tumors (gene product)
hydatidaform mole, choriocarcinoma, gestational trophoblastic tumor; CA-125: ovarian, malignant epithelial tumor; tartrate- abl (9) CML (TK) Rb (13q) retinoblastoma, osteosarcoma
resistant acid phosphatase (TRAP): Hairy cell leukemia; CA-19-9: pancreatic cancer bcl-2 follicular, undiff. lymphomas p53 (17p) most cancers, Li-Fraumeni Sz
chemical carcinogens aflatoxin (from Aspergillus): HCC; vinyl chloride: liver angiosarcoma; CCl4: centrilobular necrosis, fatty change; HER-2 or breast, ovarian, and gastric BRCA1 (17 q) breast and ovarian cancer
nitrosamines (smoked foods): stomach and esophagus; naphthalene/analine: bladder erb-B2 adenocarcinomas (TK) BRCA2 (13 q) breast ca (DNA repair protein)
Psammoma bodies: thyroid papillary adeno, ovarian serous papillary cystadeno, meningioma, mesothelioma ras colon cancer (small GTPase) p16 (9p) melanoma
mets to brain: lung>RCC>melanoma>breast>GI; liver: colon>stomach>panc>breast>lung; bone: prostate (blastic), breast (blastic and c-myc Burkitt's lymphoma (TF) APC (5q) colorectal cancer (assn w/ FAP)
lytic), lung (lytic), thyroid, testis, kidney l-myc lung tumor (TF) WT1 (11p) Wilms' tumor
n-myc neuroblastoma (TF) NF1 (17q) NFM type 1
paraneoplastics Cushing's (ACTH): SCLC; SIADH (ADH): SCLC, intracranial tumor; hypercalcemia (PTHrP): SqCLC, RCC, breast ca;
polycythemia (erythropoietin): RCC, hemangioblastoma, HCC, pheo; Lambert-Eaton (Abs against presynaptic Ca channels at NMJ): ret MEN 2A and 2B (TK) NF2 (22p) NFM type 2
thymoma, SCLC; gout or urate nephropathy (hyperuricemia due to excess nucleic acid turnover): leukemias and lymphomas; c-kit GIST (cytokine receptor) DPC (18q) pancreatic cancer
acanthosis nigricans: adenocarcinoma (usually stomach) DCC (18q) colon cancer
 Pharm/Cardio (heart is mostly β1, M2)
infusion at constant-rate reaches steady state after 4-5*t1/2 ; t1/2=0.7*(Vd/CL); 0-order: phenytoin, EtOH, aspirin GP-linked 2nd messengers
efficacy: maximal effect a drug can produce; potency: amount of a drug needed for a given effect α1 (q) vascular smooth m contraction (1B), sphincter m contraction, mydriasis
NACh: ligand-gated Na/K ch, found in all ANS presynaptic ganglia and skeletal mm; MACh: GPCR, M1-5 α2 (i) decrease sympathetic outflow and insulin release
GPCRs Gs: stimulates adenylyl cyclase, increasing cAMP, which activates PKA; Gi inhibits adenylyl cyclase; Gq activates PLC which β1 (s) increases HR, contractility, lipolysis, renin release
cleaves membrane PIP2 to IP3 (increases intracellular Ca) and DAG, both activate PKC β2 (s) same as β1 (insulin, not renin), vaso-/broncho-dilation, drops uterine tone
synapses ACh: vesamicol=packaging I, hemicholinum=reuptake I (choline), botulinum=release I; NE: reserpine= packaging I, M1 (q) in CNS, postsynaptic autonomic ganglia, gastric (ECL)/salivary secretion
cocaine/TCA/amphetamine=reuptake I, guanethidine=release I; NE's presynaptic Rs: M2, AII, α2 M2 (i) decrease HR and contractility of atria
adrenergic agonism α1 causes increase in BP not β1 (β2 effect stronger than β1, so if only β, net drop in BP [this means that β M3 (q) gut peristalsis, bladder contraction, eye (miosis, accomodation), bronchoconstriction,
agonists drop BP via β2 and β blockers also drop BP, via α2 and decreased CO]) increased exocrine secretion (DUMBLS)
CO=SV x HR; SV=EDV-ESV; MAP=CO x TPR=(2/3) x dias P + (1/3) x sys P; PP=sys-dias, is proportional to SV; Fick: rate of O2 D1 (s) relaxes renal vascular smooth m, brain
consumption = [a(O2)-v(O2)] x CO; during exercise, CO increases first from SV, then from HR D2 (i) esp in brain, modulates transmitter release
SV increased by high preload, low afterload, and high contractility (catecholamines [increase SR Ca pump activity], increased [Ca]in/ H1 (q) increased mucous production, bronchiole contraction, pruritis, pain
[Ca]out, or digitalis [indirectly inhibit Na/Ca exchanger]; decreased in acidosis) H2 (s) increased gastric acid secretion
normally, EF>55%; isovolumetric contraction=highest O2 consumption; resistance proportional to viscosity/r4 V1 (q) increased vascular smooth m contraction
JVP: a wave=atrial contraction, c wave=RV contraction, v wave=systolic filling against closed tricuspid valve V2 (s) increased water reuptake in collecting tubules of kidney
S2 splitting normal: A2 before P2, increased on inspiration; wide: A2 much before P2, small increase on inspiration, from pulmonic
stenosis/RBBB; fixed: A2 always much before P2, no change on inspiration, from ASD; paradoxical splitting: P2 before A2, decreased Murmurs
on inspiration, from aortic stenosis/LBBB Type Timing Loudest Radiation Increased intensity Cause
S3: normal in children and pregnancy, abnormal in DCM, "slosh-ing-in"; S4: HCM, "a-stiff-wall" mitral regurg |===| apex axilla hi TPR (squatting), hi RF (MR and TR), MVP,
murmur enhanced by decreased venous return (Valsalva, standing): MVP (lax chordae, but increased w/ hand grip) and HOCM LV return (expir) ischemia, LV dilation
(decreased filling, more obstruction, but decreased w/ hand grip, and no midsystolic click) TR |===| LSB RSB hi RV return (inspir) dilation, endocarditis
aortic stenosis: ejection click, pulsus parvus et tardus, LVP>>BP, later peaking (fastest flow rate) is worse MVP most | c<| apex midsys low venous return, hi myxomatous degen, RF,
pacemaker AP phase 0=Cav, slow; no plateau; 4=slow diastolic depol as Na conductance increases (If) common click TPR (hand grip) chordae rupture
ECG 5x5 box=200ms x 0.5mV; atrial repol is under QRS; PR (beginning of P to beginning of QRS)<200ms; QT (beginning of Q to end of aortic |<>| late aortic carotids or louder w/ squatting, age calcifications,
T)<400ms; QRS<120ms; U-wave: hypoK, hyperCa, hyperT4, bradycardia stenosis peak=bad apex softer w/ Valsalva bicuspid aortic valve
AFib: irregularly irregular, no discrete P waves, II or IV and warfarin; AFlutter: sawtooth, IA, IC, III (cardiovert) MS | | s== apex open snap hi LA return (expir) RF (vast majority)
AV blocks 1: long PR, asxatic; 2, type I=Wenckebach: progressive PR lengthening until dropped beat, asxatic; 2, type 2: dropped beats AR/PR | |<>== LSB bounding lower w vasodilator root dilation, RF, bicuspid
w/o change in PR, may lead to 3; 3=complete: A and V beat independently, tx=pacemaker pulses (AR) valve
ANP: high atrial P, dilates renal afferents, constricts efferents (cGMP) causing aldo-independent diuresis VSD |===| tricuspid harsh
aortic arch responds only to high BP; carotid and aortic bodies respond to pO2, pCO2, and pH; central only responds to pCO2 and pH, PDA |===|=== S2 machine-like rubella, prematurity
not pO2 (causes Cushing's triad: high ICP constricts arterioles causing ischemia, causing reflex htn, bradycardia, respiratory
depression) Angina/MI
ST-dep angina, subendocardial infarct
cyanotic ToF: pulmonary stenosis (prognostically most important), RVH, overriding aorta, VSD, "boot-shaped heart" on CXR, cyanotic
ST-elev Prinzmetal's angina, transmural infarct
spells (improved w/ squatting, decreases R to L shunt); ToGV: failure of AP septum to spiral causes separate systemic and pulmonary
circulations (aorta leaves RV), incompatible w/ life unless mixing (VSD, big ASD, PDA), assn w/ maternal DM; truncus arteriosus: AP Stage Age Criteria
septal agenesis; tricuspid atresia: no AV connection, causes hypoplastic RV, requires ASD and VSD; TAPVR: pulmonary vv drain to RA, Early mins tall T, normal ST and R
requires ASD Stage I <6hr STE (tombstone), R nl, small Q
late cyanosis Eisenmenger; VSD (commonest CHD)>ASD>PDA (uncorrected can cause differential [LE] cyanosis) Intermed >6hr STE, T-inversion, Q, loss of R
aortic coarctation infantile: preductal, assn w/ Turner's, weak femoral pulses; adult: postductal, rib notching Stage II days T-inversion, Q, ST normalizes
Stage III residual persistent Q, loss of R, T nl
arteriosclerosis Monckeberg: medial calcifications (esp radial or ulnar), no obstruction; arteroilosclerosis: hyaline thickening of small
aa (htn, DM), hyperplastic "onion-skin" in malignant htn; atherosclerosis: elastic, L-M sized aa, endothelial dysfunction causes
macrophage/LDL accumulation, forms foam cells (make fatty streaks), PDGF and TGF-β induce smooth mm migration making a Localizing MI using ECG (gold standard w/i 6h)
fibrous plaque and complex atheromanull I | II III | aVL aVF | rV4 V1 | V2 V3 | V4 V5 | V6
MI complications CHF (most deaths), arrhythmia (common acutely, through first few days), rupture (wall, papillary muscle, day 3- apical (LAD) + | | + | + | + + | + |
5=maximal), aneurysm formation, fibrinous pericarditis (3-5d post-MI), Dressler's sz anteroseptal (LAD) | | | + | + + | |
dilated/congestive/eccentric CM: from adriamycin, wet Beriberi, Cocksackie myocarditis, cocaine, Chagas' dz, daunorubicin, EtOH; anterolateral (LCX) + | | + | | | + | +
HCM: Freidrich's ataxia; restrictive/obliterative CM: granulomatous, hemochromatosis, endocardial fibroelastosis (<2yo, assn w/ posterolateral (LCX) | + | + | | | + | +
viruses [esp mumps and Cocksackie]), Loffler's Sz (eosinophils) inferior (RCA/PD) | + + | + | | | |
non-Staph endocarditis: infectious (S. bovis=colon cancer, culture negative=HACEK [H. flu, Actinobacillus, Cardiobacterium, Eikenella, RV (acute marginal) | + | + | + + | + | |
Kingella], Pseudomonas or Candida in IVDU) or non (Libman-Sacks [SLE, wart-like, benign], marantic [hypercoagulable, as in
Trousseau's]) MI markers
Kussmaul's sign: increased JVD on inspiration; RHF, constrictive pericarditis, restrictive CM (not tamponade) troponin I most specific (also PE, myocarditis), rises after 4h, peak 12h, stays 7-10d
acute pericarditis: sharp pleuritic pain, better on leaning forward, friction rub; from MI, RF, virus, uremia; chronic constrictive CK-MB non-specific, good for reinfarction on top of acute MI, gone by 3d
pericarditis: rapid jugular y-descent (spiked down), pericardial knock, pulsus paradoxus AST least specific, peaks at 2d, stays for a while
tamponade: diastolic P equilibration of all chambers; sx: hypotn, JVD, distant heart sounds, pulsus paradoxus
pulsus paradoxus systemic BP drops by >10mmHg during inspiration; 1. increased pulmonary capacity/low LV filling (all); 2. increased Evolution
RV filling causes septal deviation and reduced LV filling (pericarditis, tamponade); 3. highly negative intrathoracic P decreases Age Microscopic Changes Gross Risk
transmural P, increasing afterload (asthma, COPD, croup, apnea) day 1 4h: early coagulative necrosis; 12-24h: dark, mottled, pale w arrhythmia
RF: Ab to M protein of S. pyogenes; subQ nodules, polyarthritis (migratory), erythema marginatum, carditis, chorea; Anitschkow's contraction bands, early PMN infiltrate tetrazolium dye
cells (activated histiocytes) coalesce to form Aschoff bodies (giant cells w/i granuloma) day 2-4 extensive coagulative necrosis, acute hyperemic arrhythmia
inflammation in tissue surrounding infarct, or rupture
benign vascular tumors hemangiomas: strawberry (infancy, spontaneously regress), cherry (elderly, does not regress), pyogenic dilated vessels, PMN infiltrate (day 4)
(polypoid capillary hemangioma, can ulcerate and bleed, assn w/ trauma and pregnancy); others: cystic hygroma (cavernous
lymphangioma of neck, assn w/ Turner's sz), glomus tumor (painful, red-blue under fingernail, from smooth mm), bacillary day 5-10 ingrowth of granulation tissue as macro- hyperemic border, rupture (wall,
angiomatosis (Bartonella henselae, PMNs) phages degrade old structure and induce scar centrally yellow- chordae)
formation brown
malignant vascular tumors angiosarcoma (liver, highly lethal, assn w/ vinyl chloride, As, Thorotrast [ThO2]), lymphangiosarcoma
(caused by persistent lymphedema, post-radical mastectomy, eg), Kaposi's (lymphocytes) wk 7 scar grey white aneurysm
CABG LAD only=L internal mammary (thoracic); multiple=great saphenous (medial foot to inf. pubic tubercle)

Endocrine
neurophysins=carrier proteins from hypothalamus to posterior pit; α-subunit identical for TSH, FSH, LH, β-hCG Signalling pathways of hormones
pancreas: more endocrine cells in tail, αs peripherally, βs centrally, δs interspersed; TRH -[+]> TSH and PRL cAMP Ca (PTH, calcitonin), ADH (V2R)/α-subunits (FSH, LH, TSH, β-hCG), melanotropic
(ACTH, MSH), pancreatic (glucagon), GHRH
insulin inhibits glucagon release, increases glucose transport (GLUT-4=insulin-responsive, in adipose and skeletal mm; GLUT-1=RBC
and brain; GLUT-2=liver, small intestine, cornea, kidney, β-cells), increases Na retention, increases cellular K uptake; enters β-cell via cGMP NO, ANP IP3 α-subunitRH (GnRH, TRH), posterior pit (oxytocin, ADH)
GLUT-2, aerobic respiration (RLS=glucokinase), ATP binds to K channel and closes, causing depolarization and Ca channel opening, nuclear T3/T4 cytosolic all steroids but T3/4: DHT, P, E2, D3, cortisol, aldo
causing exocytosis of insulin intrinsic TK (MAP kinase) -GF: FGF, PDGF, IGF-1, insulin (with IGF-1);; TK P-ation
(inhibited by TNF-α) recruits SOS protein, Ras hydrolyzes GTP and becomes activated
DM type 1: assn w HLA-D3/4, anti-glutamate decarboxylase Abs; acute sx: DKA (higher insulin requirement not met causes ketosis;
receptor TK (JAK/STAT) GH, PRL, IL's, CSF
Kussmaul breathing, N/V, abd pain, psychosis/delerium, dehydration, fruity breath odor, AGMAc, hyperkalemia [depleted
intracellular]); chronic sx: small vessels (BM thickening causing retinopathy, neovascular glaucoma, nephropathy [nodular sclerosis,
proteinuria, CRF, htn, Kimmelstiel-Wilson nodules]), large vessels (CAD, PVD, gangrene), osmotic damage (neuropathy, sorbitol DM dx
cataracts) HbA1C Fasting glucose 2h glucose tolerance
Normal <6.0% <110 <140
adrenals vertical: chlsl -[desmolase]-> /(17-OH)/pregnenolone -[3β-OHsteroid DH]-> /(17-OH)/progesterone -[21-OHase]-> 11-
deoxycorti-/(sol)/costerone -[11-β-OHase]-> corti-/(sol)/costerone -[aldo synthase]-> aldo; DHEA to androstenedione (can be Pre-diabetic 6.0-6.4% 110-126 140-200
converted peripherally to estrone and estradiol) to testosterone (converted by 5α-reductase to DHT or aromatase to estradiol); Diabetic >6.5% >126 >200
desmolase activated by ACTH, inhibited by ketoconazole or sx of hyperglycemia and a casual (random) plasma glucose >200
cortisol: increases gluconeogenesis, lipolysis, proteolysis, and α-1 on arterioles (maintains BP), decrease bone formation and immune
function, anti-inflammatory; excess tested by dexamethasone suppression test CAH (all have enlarged adrenal glands due to low cortisol and thus high ACTH)
hyperaldo primary=Conn's: aldo-secreting tumor, htn, hypokalemia, MAlk, may be bilateral; secondary: all cause kidney to perceive Deficiency Epidem Sex Hrmns Aldo BP Other
low V (renal artery stenosis, CHF, CRF, cirrhosis, nephrotic sz), so secretes high renin 21-OHase 95% high low low hypovolemic shock in newborn
11βOHase 5% high low high masculinization, as w 21-OHase
adrenal insufficiency 1°: (acute=Waterhouse-Friderichsen Sz: hemorrhage from N. meningitidis sepsis, DIC, shock), usually
chronic=Addison's dz: can be from atrophy or destruction, def of aldo and cortisol, sx=hypotn, hyperK, acidosis, skin 17αOHase rare low high high M=pseudoherm, F=sexual infant
hyperpigmentation (from high ACTH binding to MSHRs); 2°: low CRH or ACTH production: no skin hyperpigmentation, no hyperK;
corticosteroid withdrawal can cause acute or chronic insufficiency Multiple endocrine neoplasias (MEN)
neuroblastoma: kids, can be anywhere along sympathetic chain, elevated HVA in urine, less likely to have htn, n-myc=worse MEN 1 (Wermer's) parathyroid (kidney stones), pituitary (usually PRL or GH), and pancreas
prognosis; pheo: adults, high urine VMA, episodic htn, headache, perspiration, palpitations, tachycardia, pallor, assn w/ NFM, MEN tumors (Zollinger-Ellison, so stomach ulcers)
2A/B, 10%: malignant, bilateral, extra-adrenal, calcify, kids, familial MEN 2A (Sipple's) medullary thyroid cancer, pheo, parathyroid (kidney stones)
PTH chief cells of paraT, PTH inhibited by low Mg (diarrhea, rxs [AG, EtOH, diuretics]); renal PO4 resorption down, ups renal Ca MEN 2B medullary thyroid cancer, pheo, oral or intestinal ganglioneuromatosis
resorption (DCT), stimulates osteoblasts (secrete RANK-L [stimulates osteoclasts, ups bone resorption, raising blood Ca and PO4] and (marfanoid habitus)
M-CSF), stimulates kidney 1α-OHase (inhibited by calcitriol) MEN 2A and MEN 2B associated w/ ret gene (oncogene, tyrosine kinase)
vit D D2=ergocalciferol, from plants; D3=cholecalciferol, from sun, 24,25-(OH)2 vit D=inactive; 1,25-(OH)2 (calcitriol) increases
intestinal Ca and PO4 absorption and stimulates osteoblasts in the same way as PTH
T3/T4: synthesized by peroxidase from I + tyrosine (inhibited by anions and PTU or methimazole);
hyperPTH 1°: usually adenoma, hypercalcemia, stones, hypoPO4, high alk phos, high cAMP in urine, can cause osteitis fibrosa cystica bone growth, CNS maturation, increased β1 in heart, increased metabolic rate; TBG increases in
(cystic bone spaces filled w brown fibrous tissue); 2°: decreased gut Ca absorption, high plasma PO4 (usually from chronic kidney OCP-use and pregnancy
failure) causes hyperplasia, sx=hypocalcemia, hyperPO4, high alk phos; 3°: refractory hyperPTH from chronic renal dz, hypercalcemia; hyperT3 pretibial myxedema; toxic multinodular goiter: hot nodule, mutated TSH-R, rarely
2°/3° can cause renal osteodystrophy malignant; Grave's: presents during stress, type II hypersensitivity; thyrotoxicosis: complication of
hypoPTH usually from accidental excision, autoimmune, or DiGeorge; hypocalcemia, tetany, Chvostek's sign (tapping facial n causes hyperT3, stress-induced catecholamine surge, death by arrhythmia; Jod-Basedow: thyrotoxicosis if a
mm contraction), Trousseau's sign (occlusion of brachial a w/ BP cuff causes carpal spasm); pseudohypoPTH=Albright's hereditary pt w/ I-def goiter is made I-replete
osteodystrophy: AD kidney unresponsiveness to PTH
calcitonin: parafollicular (C-) cells of thyroid, decrease bone resorption of Ca, not important physiologically
hypoT3 myxedema (facial/periorbital), severe=myxedema coma (hypothermia and altered mental
DI no ADH response, USG<1.006, serum>290mOsM; central (from supraoptic nuc): pit tumor, trauma, surgery, or histiocytosis X,
status), can be a side effect of lithium or amiodarone; Hashimoto's: thyroiditis, so may be hyperT3
responds to desmopressin; nephrogenic: hereditary, 2° to hypercalcemia, demeclocycline, Li, doesn't respond to desmopressin; ADH
early, autoimmune (antimicrosomal antithyroglobulin Ab, HLA-DR5), Hurthle cells, lymphocytic
responds to Osm before V, acts in medullary collecting duct
infiltrate w/ germinal centers; cretinism: severe fetal hypoT3, co-endemic with goiter, pot-bellied,
SIADH: excessive water retention, hypoNa, urine Osm>serum Osm, low aldo; can be from ectopic production, head trauma, pale, puffy faced, protruding umbilicus, protuberant tongue; subacute thyroiditis (de Quervain's):
pulmonary dz, or rxs (carbamazepine, cyclophosphamide); tx=demeclocycline, water restriction self-limited, following flu-like illness, jaw pain, early inflammation (granulomatous), tender; Riedel's
thyroiditis: replaced by fibrous tissue, rock-hard
 hypoT3 myxedema (facial/periorbital), severe=myxedema coma (hypothermia and altered mental
status), can be a side effect of lithium or amiodarone; Hashimoto's: thyroiditis, so may be hyperT3
early, autoimmune (antimicrosomal antithyroglobulin Ab, HLA-DR5), Hurthle cells, lymphocytic
infiltrate w/ germinal centers; cretinism: severe fetal hypoT3, co-endemic with goiter, pot-bellied,
SIADH: excessive water retention, hypoNa, urine Osm>serum Osm, low aldo; can be from ectopic production, head trauma, pale, puffy faced, protruding umbilicus, protuberant tongue; subacute thyroiditis (de Quervain's):
pulmonary dz, or rxs (carbamazepine, cyclophosphamide); tx=demeclocycline, water restriction self-limited, following flu-like illness, jaw pain, early inflammation (granulomatous), tender; Riedel's
pit adenoma usually PRL (amenorrhea, galactorrhea), then GH (insulin resistance, dx=glucose suppression) thyroiditis: replaced by fibrous tissue, rock-hard
NET: most common tumor of appendix, secrete 5-HT, high 5-HIAA in urine, 1/3 (met, multiple, present w/ 2nd malignancy); carcinoid thyroid cancer papillary: most common, excellent prognosis, "Orphan Annie" nuclei (ground glass),
sz: recurrent diarrhea, cutaneous flushing, asthmatic wheezing, R-sided valvular dz, especially metastatic NETs from small bowel, not nuclear grooves, psammoma bodies; follicular: uniform follicles, good prognosis; medullary: from C
seen if tumor vessels go to liver (5-HT eliminated first pass) cells, sheets in amyloid stroma, assn w/ MEN2A/B; undifferentiated/anaplastic: very poor;
Zollinger-Ellison Sz: gastrin-secreting tumor of pancreas or duodenum, acid hypersecretion, thickened rugae, recurrent ulcers, assn lymphoma: assn w/ Hashimoto's
w/ MEN 1; VIPoma: panc tumor, copious diarrhea (sphincter relaxation, H2O excretion) low T4 to T3: PTU, glucocorticoids, amiodarone, iopanoate, non-selective β-blockers

GI
fetal umbilical vein becomes ligamentum teres (in falciform), hepatoduodenal lig contains portal triad GI hormones/secretions
submucosal plexus=Meissner's; myenteric plexus=Auerbach's (inner circular, outer longitudinal mm fibers) Hormone Source Regulation Action Other
duodenum: Brunner's (submucosal) glands, crypts of Lieberkuhn (continue into ileum); [goblet cells] highest in jejunum; aorta: gastrin G cells up: AAs, peptides, up: (ECL) gastric H+ ectopic production=
T12=celiac; L1=SMA, renal aa (L=lower); L2=gonadal aa (L=higher); L3=IMA; L4=bifurcation (antrum) stomach distention/ secretion, mucosal Zollinger-Ellison Sz; AAs:
alkalinizat'n, vagal growth, motility, & Phe and Try are potent
short gastric aa: from splenic a, supply fundus, poor anastamoses; block of abdominal aorta can use these anastamoses: S epigastric stimulation (GRP) stimulators
(internal thoracic) to inf epigastric (external iliac), S pancreaticoduodenal (celiac) to inf. PD (SMA), middle colic (SMA) to left colic parietal hyperplasia
(IMA), superior rectal (IMA) to middle rectal (internal iliac) secretin S cells (D) up: acid/FAs in up: bile and panc
femoral lateral to medial to find NAVEL; triangle (made of SAIL) has all, but sheath doesn't contain the nerve duodenum bicarb secretion;
down: H+ secretion
hernias diaphragmatic: (congenital=pleuroperitoneal membrane defect), usually hiatal (stomach; sliding [GE jctn displaced] or
paraesophageal [cardia into thorax]); direct: through inguinal (Hesselbach's) triangle (medial to inferior epigastric a), goes through GIP K cells up: FA, AAs, oral up: insulin secret'n; incretin
external inguinal ring; indirect: M>F, congenital, through deep inguinal ring, failure of processus vaginalis to close, can form (D/J) glucose down: H+ secretion
hydrocele; femoral: F>M, thru femoral canal CCK I cells (D/J) up: FA, AAs up: panc secretion, GB acts on neural muscarinic
contract'n, tone of pathways to stimulate
saliva parotid (serous), sublingual (mucinous); stimulated by parasympathetic (VII, IX) and superior cervical ganglia (T1-3); α-
pyloric sphincter the panc
amylase/ptyalin (α-1,4 hydrolysis get disaccharides [maltose & α-limit dextrins], inactivated by low pH), bicarb, mucins (lubrication),
antibacterial, epithelial GFs; low flow rate=hypotonic (reabsorb NaCl) somato- δ cells up: acid; down: vagal down: everything anti-GH effects
salivary gland tumors usually in parotid; pleomorphic adenoma: most common, painless, movable, high rate of recurrance; Warthin's statin (panc/GI) stimulation
tumor: benign, heterotopic salivary tissue in LN; mucoepidermoid carcinoma VIP paraS up: distention, vagal up: sphincter relax- VIPoma: panc tumor,
gastric acid secretion: H/K ATPase, H produced by carbonic anhydrase, bicarb exchanged for Cl basolaterally ganglia stimulation ation, water excret'n copious diarrhea
pancreas α-amylase & lipase secreted in active form, colipase (activated by trypsin) necessary for lipase to be effective; entero- Motilin Sm bowel up: fasting state makes MMCs agonists useful
kinase/-peptidase (duodenal excretion) activates trypsinogen, which activates all proteases intrinsic parietal B12 binding protein autoimmune attack=
oligosaccharides: hydrolases at brush border of intestine, RLS in carb digestion, makes monosaccharides; absorption: glucose and factor cells (uptake in ileum) chronic gastritis/PA
galactose by SGLT1 (Na dependent), fructose by GLUT-5; all basolaterally use GLUT-2 gastric acid parietal up: M3R (ACh), H2R, decreases stomach pH
Peyer's patches: unencapsulated, specialized M cells take up Ag, BCs differentiate to IgA-secreting; bile: bile salts (acids conjugated cells gastrin; down: SS, GIP,
to glycine or taurine), phospholipids, chlsl (only method of excretion), bilirubin, water PG, secretin
pepsin chief cells up: local H+, vagal protein digestion pepsinogen to pepsin by
esophagus varices: painless bleeding of submucosal veis; achalasia: loss of myenteric plexus, NO implicated, Chagas', CREST; Mallory-
Weiss Sz: mucosal lacerations at GE jctn from severe vomiting (alcoholics, bulemics), hematemesis; Boerhaave Sz: transmural stimulation H+
esophageal rupture from violent retching; Plummer-Vinson: webs (dysphagia), glossitis, Fe def anemia; Barrett's: intestinal bicarb mucosa, up: secretin (acts on neutralize acid bicarb is trapped in
metaplasia; esophagitis: from bisphosphonates Brunner's pancreatic and biliary mucous that covers
glands secretions) gastric epithelium
esophageal cancer risk factors: achalasia, Barrett's, cigarettes, diverticuli, EtOH/esophageal web/esophagitis; SqCC (most common
worldwide) mostly upper-middle 1/3, adenoca (most common US) mostly lower 1/3
IBD
malabsorption abetalipoproteinemia; pancreatic insufficiency: CF, obstruction, chronic panc; disaccharidase def: osmotic diarrhea,
Crohn's (disordered response to flora) UC (autoimmune)
can be self-limited after insult; Whipple's dz; tropical sprue: similar to celiac sprue, but responds to abx and affects whole small
bowel; celiac sprue: auto-Abs to gluten (gliadin, prolamin) and TTG (tissue transglutaminase), causes blunting of vili, crypt Location usually terminal ileum, skip lesions, rectal continuous, always involves rectum
hyperplasia, and lymphocyte infiltrate (lamina propria) in proximal bowel, associated with dermatitis herpetiformis and increased risk sparing
of TC lymphoma Gross cobblestone mucosa, creeping fat, bowel wall friable mucosal pseudopolyps, loss of
gastritis acute/erosive: NSAIDs (RA), EtOH, uremia, burns (Curling's), brain injury (Cushing's); chronic: type A (body/fundus: Abs to thickening, linear ulcers/fistulas haustra
parietal cells) and type B (antrum: most common, H. pylori infxn, increased risk of MALT) Micro-scopic transmural inflammation, noncaseating sub-/mucosal inflammation only,
PUD clean margins; gastric: decreased mucosal protection, greater pain w/ meals, H. pylori in 70%; duodenal: increased gastric granulomas, lymphoid aggregates crypt abscesses/ulcers
secretion and decreased mucosal protection, pain decreased with meals, H. pylori in 100% Complic- malabsorption, strictures, fistulas, colo-rectal malnutrition, toxic megacolon,
ations cancer (minorly increased risk) colorectal carcinoma (hi risk)
stomach cancer: 95% adenoca, early spread locally and mets to LNs/liver (Virchow's node=L supraclavicular; Krukenberg's
tumor=bilateral mets to ovaries; Sister Mary Joseph's nodule=subQ periumbilical met); assn w/ nitrosamines, achlorhydria, chronic Sx diarrhea ± blood, erythema nodosum, bloody diarrhea, PSC, pyoderma
gastritis; signet ring cells, acanthosis nigricans; linitis plastica=diffuse migratory polyarthritis, immunologic disorders gangrenosum, ankylosing spondylitis,
uveitis
appy: kids=lymphoid hyperplasia after viral infxn, adults=fecalith; ddx: ectopic, Y. enterocolitis, diverticulitis (LLQ pain, fever,
leukocytosis, BRBPR, can cause colovesical fistula [pneumaturia, cystitis], peritonitis; tx=abx) tx corticosteriods, infliximab ASA, 6-MP, infliximab, colectomy
Meckel's diverticulum: most common congenital GI anomaly, yolk stalk persistence, 2" long, 2' from ileocecal jctn, 2% of pop,
commonly presents in first 2y, may contain 2 mucosae (gastric/panc); dx=pertechnetate study drugs causing GI path: macrolides=acute cholestatic hepatitis; INH=hepatitis; hepatic necrosis:
intussusception: usually kids (adenovirus), in adults=intraluminal tumor; volvulus: usually elderly halothane, valproate, acetaminophen, Amanita mushroom poisoning
Hirschsprung dz: failure of neural crest cells to migrate, causes congenital megacolon, always involves rectum GI pathology
angiodysplasia: tortuous dilation of vessels, bleed; usually ileum/R-sided, older pts Marker Use
Aminotransferases hepatocyte damage (virus: ALT>AST; alcohol: AST>ALT), MI (AST)
polyps 90% are non-neoplastic; neoplastic: adenomatous, villous, juvenile polyposis sz, Peutz-Jeghers Sz (AD, hamartomas
throughout GI, hyperpigmented mouth, lips, hands, genitals, increased risk of CRC), FAP (AD APC mutation, pancolonic, always GGT (glut cholestasis, >2x ULN
involves rectum; Gardner's, Turcot's), HNPCC (aka Lynch Sz, AD DNA mismatch repair defect, always involves proximal colon); transpep- w/ heavy EtOH
distal=obstruction, hematochezia; proximal=dull pain, anemia tidase) consumption

CRC: higher risk with IBD, S. bovis sepsis, use CEA tumor marker; 1. microsatellite instability (by mismatch repair gene mutations); 2. alk phos bone dz, cholestasis
APC mutation (decreased cellular adhesion, increased prolif via β-catenin), KRAS mutation (unregulated intercellular signal (biliary dz/obstruc-
transduction) causes adenoma, loss of p53 marks carcinoma tion, macrolides)

micronodular cirrhosis: <3mm nodules, from metabolic insult (EtOH, macrolides); macronodular: >3mm nodules, significant liver amylase acute panc, mumps
injury causing hepatic necrosis (infxn, halothane, acetaminophen, valproate), HCC lipase acute panc (specific)
EtOH hepatic steatosis: moderate intake causes short term, macrovescicular change, reversible; hepatitis: long-term EtOH, Jaundice pre-HC (hemolysis) hepatocellular post-HC (obstructive)
swollen/necrotic hepatocytes, PMN infiltrates, Mallory bodies (intracytoplasmic eosinophilic inclusions, "twisted-rope"); cirrhosis: conj blood bilirubin low (all unconj) some (some unconj) high
micronodular "hobnail", sclerosis around central vein (zone III) urine bilirubin low (not soluble) high (some conj) highest
HCC: jaundice, tender HSM, ascites, hypoglycemia, polycythemia, Budd-Chiari; spreads hematogenously, AFP urine bilinogen high nl/low low
α1-AT def: misfolded gene product, decreased elasticity of lungs (panacinar emphysema) and PAS-positive globules in the liver heme to unconjugated bilirubin in macrophage, albumin carries (complex=indirect bilirubin) to liver,
(cirrhosis and liver failure); codominant trait conjugated by UDP glucuronyl transferase to direct bilirubin, into biliary lumen by glucuronyl
hemochromatosis=dz caused by hemosiderosis (Fe deposition)=micronodular cirrhosis, "bronze diabetes" (DM, skin pigmentation), transferase, and broken down in gut to urobilinogen
CHF, HCC; may be 1° (AR HFE mutation, transferrin R on basolateral enterocyte, binds plasma transferrin to sense blood Fe
concentrations, adjust abs) or 2° (chronic transfusions); assn w/ HLA-A3
pancreatitis acute: autodigestion; obstruction (gallstones, ERCP), overworked (EtOH, hypercalcemia,
biliary tract dz sx=pruritis, jaundice, dark urine, light stools, HSM; labs=high direct bilirubin, chlsl, GGTP, alk phos; PSC: idiopathic hyperTGemia), mumps, trauma, autoimmune, drugs (sulfa, steroids); sx: epigastric abd pain
concentric "onion skinning" fibrosis causes "beads on a string" of any bile ducts, assn w/ hyperIgM, ulcerative colitis; PBC: anti- radiating to back, anorexia, N, elevated lipase (more specific) and amylase; can cause DIC, ARDS,
mitochondrial Abs causes PMN infiltrate, granulomas; SBC: high intraductal pressure from obstruction causes fibrosis and stasis, diffuse fat necrosis, hypoCa, pseudocyst, infxn, hemorrhage, multiorgan failure; chronic: can cause
complication=ascending cholangitis pancreatic insufficiency (ADEK deficiency, steatorrhea, DM), calcified assoc'd w/ EtOH, smoking,
pancreatic cancer
cholelithiasis 4Fs, high chlsl/bilirubin, low bile salts, stasis; chlsl: 80% of stones, radiolucent (but 15% are calcified); pigment:
radiopaque, assd w/ chronic hemolysis, alcoholic cirrhosis, biliary infxn (Clonorchis, Salmonella); can cause cholecystitis (Murphy's pancreatic adenoca: CEA and CA-19-9 markers, NOT assoc'd w/ EtOH; sx: abd pain radiates to back,
sign), ascending cholangitis (Charcot's triad: jaundice, fever, RUQ pain), pancreatitis, biliary colic (can be painless in DM), fistulas, weight loss, Trousseau's, jaundice, palpable GB (Courvoisier's sign)
gallstone ileus (usually ileocecal jctn) acute calculus cholecystitis: obstruction, chemical irritation, mucous disruption, bile acid attack on
mucosa, PG release, hypomotility, distension, ischemia, bacteria

Heme/Onc
eosinophils: major basic protein (anti-helminth), histaminase and arylsulfatase (limit reaction after mast cell degranulation); Hemolytic anemia (high LDH)
eosinophilia=NAACP: neoplasm, allergy, asthma, collagen vascular dz, parasites (Loffler's) Intravascular: low haptoglobin, Hb in urine, not usually jaundiced
basophil: granules of heparin, histamine, and vasoactive amines (LT); mast cell: + eosinophil chemokines G6PDD trigger: fava beans, infxn, INH, sulfa, anti-malarial, aspirin, ibuprofen, nitrofurantoin;
agranulocytosis=granulocytopenia: PTU/methimazole, colchicine, carbamazepine, clozapine, dapsone back pain, Heinz bodies, and bite cells
platelet plug formation vWF binds subendothelial collagen, platelets bind vWF (GpIb), release dense granules (Ca [necessary for PNH glycophosphatidyl inositol links decay accelerating factor onto RBC membrane,
coagulation cascade], ADP [helps platelets adhere to endothelium and induces GpIIb/IIIa to platelet surface]), fibrinogen binds prevents complement cascade; high urine hemosiderin
GpIIb/IIIa, links platelets; aggregation: pro=TXA2 (platelets), anti=PGI2 angio-pathic schistocytes; micro-: from DIC, HUS (Shiga toxin), SLE, malignant htn; macro:
prosthetic valves, aortic stenosis
coagulation cascade XIIa activates XI and prokallikrein; kallikrein=serine protease, breaks down HMWK ([XII activator] to bradykinin
[vasodilation, pain]) and plasminogen (to plasmin, which activates C3a and degrades fibrin); Ca and phospholipid needed for all infxn malaria, Babesia
factor activation but XII, VIII, V, and I; IIa=thrombin, Ia=fibrin; protein S activates protein C, which inactivates Va, VIIIa; tPA + vWF Extravascular: cleared in spleen; high unconjugated bilirubin, jaundice; (Wilsons)
from endothelial cells, vWF protects VIII sickle cell glu to val on β gene; marrow expansion, aplastic crisis (B19), bone crises, renal
coagulopathy hemophilia: A=VIII, B=IX; vit K def/warfarin=loss of cofactor for γ-carboxyglutamation rxn, inactive II, VII, IX, X, C, S; (HbS) papillary necrosis/microhematuria, splenic sequestration crisis, autosplenectomy
Bernard-Soulier: GpIb def; Glanzmann thrombasthenia: def GpIIb/IIIa; ITP: anti-GpIIb/IIIa Abs, increased megakaryocytes; TTP: (Howell-Jolly bodies, Salmonella osteomyelitis)
ADAMTS 13 def (vWF metalloprotease), vWF multimers, clots, schistocytes, pentad=neuro/renal sx, fever, thrombocytopenia, HbC def glu to lys, compound heterozygotes w/ HbSC have milder dz than HbSS
microangiopathic hemolytic anemia; vW dz: mild, AD; factor V Leiden: Va resistant to APC; C/S def: risk of thrombotic skin
sphero- hereditary def in cytoskeletal elements (ankyrin, band 3.1, spectrin); high MCHC, high
necrosis/hemorrhage w warfarin
cytosis RDW, SM, aplastic crises; tx=splenectomy (Howell-Jolly body)
DIC causes: sepsis (GN), trauma, OB complications, acute pancreatitis, malignancy, nephrotic sz, transfusion PK def AR, pyruvate kinase def, low ATP, rigid RBC membrane; HA in newborn
microcytic hypochromic anemia MCV<80, basophilic stippling of RBCs; Fe deficiency (duodenal abs), anemia of chronic dz, auto- spherocyte; warm=IgG: SLE, CLL, α-methyldopa; cold=IgM: CLL, mono, M. pneumo;
thalassemia (α: 3 mutations=HbH (β4); β: high HbF, minor [asxatic, high HbA2] or major [severe anemia, 2° hemochromatosis, immune hydrops fetalis; usually Coomb's positive (direct=anti-IgG Ab)
marrow expansion, chipmunk facies]), Pb poisoning, sideroblastic anemia
Hemoglobin types
macrocytic anemia MCV>100, macroovalocytic RBCs, impaired DNA synth; megaloblastic: hypersegmented PMNs, glossitis, high Variant Make-up When present
homocysteine; folate def: jejunal abs, normal methylmalonate, seen w/ MTX, TMP, hemolytic anemia, pregnancy; B12 def: Schilling
HbA α2β2 normally 95% of Hb
test, ileal abs, D. latum, causes neuro sx (subacute combined degeneration of posterior columns, peripheral nerves, lateral
HbA1C α2β2 non-enzymatic glycation of normal Hb, <6%, higher in DM
corticospinal, dementia), koilonychia; also orotic aciduria, phenytoin, MTX, sulfa; nonmegaloblastic: liver dz, alcoholism,
reticulocytosis, metabolic disorder (nucleotide synthesis def, ornithine transcarbamoylase def), AZT, 5-FU, flucytosine, hydroxyurea HbA2 α2δ2 normally 3% of Hb, higher in beta-thal minor
HbC α2βC2 beta variant, mild hemolytic anemia
HbE α2βE2 beta variant, mild hemolytic anemia
normocytic, normochromic anemia aplastic anemia (destruction of myeloid stem cells causes severe pancyto-penia with normal cell
morphology, hypocellular marrow with fatty infiltrate; radiation, drugs [benzene, chloramphenicol, NSAIDs, PTU/methimazole,
antimetabolytes], viral [B19, EBV, HIV, HCV], Fanconi's anemia [congenital], idiopathic [immune mediated, may follow acute
hepatitis]), kidney dz, anemia of chronic dz, HA
normocytic, normochromic anemia aplastic anemia (destruction of myeloid stem cells causes severe pancyto-penia with normal cell
morphology, hypocellular marrow with fatty infiltrate; radiation, drugs [benzene, chloramphenicol, NSAIDs, PTU/methimazole, HbF α2γ2 normal in fetal, higher in sickle cell
antimetabolytes], viral [B19, EBV, HIV, HCV], Fanconi's anemia [congenital], idiopathic [immune mediated, may follow acute Barts γ4 alpha-thal
hepatitis]), kidney dz, anemia of chronic dz, HA HbS α2βS2 beta variant, sickle cell
abnormal RBCs acanthocyte: liver dz (abetalipoproteinemia); target cell: high SA:V ratio (high membrane, low heme=HbC, asplenia, Gower 1 ζ2ε2 early embryonic stage
liver dz, thalassemia); Heinz bodies: ferric heme pption, in α-thalassemia, G6PDD Gower 2 α2ε2 late embryonic stage
porphyria glycine + succinyl-CoA -[B6, δ-ALA synthase, RLS (sideroblastic anemia)]-> δ-aminolevulinic acid (aka δ-ALA) -[δ-ALA
dehydratase (Pb poisoning)]-> porphobilinogen -[porphobilinogen deaminase (acute intermittent porphyria)]->hydroxymethylbilane- Lab values in anemia: primary cause in red
>uroporphyrinogen III-[uroporphyrinogen decarboxylase (porphyria cutanea tarda)]-> coproporphyrinogen III -> protoporphyrin -[+ Serum Fe Transferrin or TIBC Ferritin % transferrin sat (serum
Fe, ferrochelatase (Pb poisoning)]-> heme (feeds back onto δ-ALA synthase); porphobilinogen & uroporphyrinogen are converted to
("tissue need") (storage) Fe/TIBC)
uroporphyrin
Fe deficiency low high low low
P. cutanea tarda: most common, tea-colored urine, blistering cutaneous photosensitivity; acute intermittent P.: red-wine colored chronic dz low low high nl
urine, abd pain, polyneuropathy, psych disturbances, ppted by rxs, tx=glucose and heme hemochromatosis high low high high
pregnancy/OCPs nl high nl low
Hodgkin's: contiguous spread through nodes, constitutional B sxs, mediastinal LAD, M>F, good prognosis=high lymphs, few Reed-
Sternberg cells (binucleate, "owl eye", CD30+, CD15+); nodular sclerosing (most common, RSC=lacunar, collagen banding lead poisoning high low nl high
surrounding nodules), mixed cellularity (more RSCs), lymphocyte predominant (rare), lymphocyte depleted (very rare, high RS to Pb poisoning: microcytic/sideroblastic anemia, basophilic stippling of RBCs, renal, GI dz; kids: neuro
lymphocyte ratio, older men, poor prognosis) deterioration, wrist/foot drop, Pb lines on gums/long bones (XR), abd pain; adults (usually work-
lymphoma diffuse large cell lymphoma: most common NHL, usually in elderly (20% kids), mostly BC (20% TC); BC: Burkitt's: young, related): headache, memory loss, demyelination
starry sky appearance (sheets of lymphs, interspersed macrophages); mantle cell: older, poor prognosis, CD5+; follicular: bcl-2,
indolent; TC: adult TC: HTLV1, aggressive, cutaneous lesions; Sezary sz Translocations
multiple myeloma: commonest 1° bone tumor, monoclonal plasma cell (fried egg), IgG>IgA, infxn-prone, lytic bone lesions Leukemia/lymphoma AML M3 CML Burkitt's Follicular Mantle Ewing's
(hypercalcemia), M-spike, anemia, renal failure (Bence Jones proteins, AL [1° amyloid]), rouleaux Translocation t(15;17) t(9;22) t(8;14) t(14;18) t(11;14) t(11;22)
Waldenstrom's macroglobulinemia: hyperIgM, hyperviscosity sx; MGUS: monoclonal expansion, no sx Activated product - bcr-abl c-myc bcl-2 - -
ALL: kids, marrow involvement/mediastinal mass, lymphoblasts, TdT+ (pre-T/-BC), CALLA+, therapy responsive (esp if t(12;21)); hairy
cell: middle aged; CLL: >60yo, asxatic, smudge cells in smear; Small LL: no lymphocytosis Polycythemia primary cause in red
AML: Auer rods (fused granules), myeloblasts; AML M3: responds to all-trans vit A (induces differentiation); CML: Philadelphia plasma V RBC mass O2 sat EPO associated dzs
chromosome=t(9;22), bcr-abl, granulocytosis, metamyelocytes, SM, can have blast crisis (AML or ALL), low alk phos (differentiate relative low nl nl nl
from leukemoid rxn), responds to imatinib (TK inhibitor) appropriate absolute nl high low high lung dz, CHD, altitude
Langerhans cell histiocytosis: S-100+, CD1a+, Birbeck granules (tennis rackets) on EM; can cause DI inappropriate abs. nl high nl high ectopic erythropoietin
chronic myeloproliferative disorders (other than CML) all have JAK2 mutations in stem cell; polycythemia vera: mutation in early cell, polycythemia vera high high nl low
pancytosis; essential thrombocytosis: specific for megakaryocytosis; myelofibrosis: fibrotic obliteration of marrow, teardrop RBCs,
anemia, platelets/WBCs variable, megakaryocytes implicated

Musculoskeletal
zona occludens: claudins & occludins; zona adherens (intermediate jctn): below occludens, cadherins bind actin (Ca-dependent); Upper extremity nerve lesions
macula adherens (desmosome): cadherens bind intermediate filaments; integrins to BM Nerve Root Motor Deficit Sensory Deficit Injury
rotator cuff: supraspinatus (abduction before deltoid, most common cuff injury), subscapularis (adduction and medial rotation), Axillary C5-6 shoulder abduction over shoulder humerus dislocation,
infraspinatus and teres minor (adduction and lateral rotation) (deltoid) surgical neck break

other nerve lesions Erb's palsy (waiter's tip): upper trunk (C5-6), paralysis of abductors, lateral rotators, and biceps (so pronated); MusCutan C5-7 elbow flexion lateral forearm upper trunk
posterior cord; deltoid paralysis + wrist drop; long thoracic n: winged scapula; thoracic outlet sz (cervical rib): Klumpke's palsy and Radial C5-8 extensors, brachio- posterior arm, dorsal hum. midshaft break,
disappearance of radial pulse on moving head ipsilaterally radialis, supinator hand/thumb Saturday night palsy

skeletal/cardiac mm contraction nAChR causes depol, travels down T-tubule, activates DHPR, lets in Ca, Ca activates ryanodine R on Median C5-T1 thumb opposition, dorsal + palmar lateral carpal tunnel, lunate
SR, more Ca release, Ca binds troponin C, moves tropomyosin from myosin-binding sites on actin; H-/I-bands shrink, A doesn't; type (distal) lateral MCP flex'n 3 1/2 fingers dislocation
1=slow, red; type 2=fast, white (hypertrophy, don't switch) Median C5-T1 + lateral DIP/PIP dorsal + palmar lateral supracondylar humerus
smooth mm contraction membrane depol, Cav (DHP, L-type) open, Ca binds calmodulin, activates myosin light chain kinase (MLCK), (proxim.) flexion, wrist flex'n 3 1/2 fingers fracture
P-ation, cross bridge formation; cGMP inhibits MLCK, MCLPhosphorylase inactivates Ulnar (distal) C8-T1 interossei, thumb adduction, lumbricals 4 and fracture of the hook of
achondroplasia: constitutive FGFR3 inhibits chondrocyte prolif, failure of long bone growth (endochondral ossification, short limbs), 5; sensory: medial 1 1/2 fingers the hamate
membranous ossification fine (big head); AD, but 85% sporadic (hi paternal age) Ulnar C8-T1 + wrist flexion medial 1 1/2 fingers medial epicondyle of
nl bone labs osteoporosis: reduction of spongy bone mass despite normal bone mineralization; I=menopause; II=age; vertebral crush (proxim.) humerus, funny bone
fracture, femoral neck, distal radius (Colle's); corticosteroids, heparin, homocystinuria Klumpke C8-T1 +all lumbricals; sensory: medial forearm lower trunk (birth)
nl bone labs (cont'd) osteopetrosis: carbonic anhydrase II def, no osteoclast fctn, failure of nl resorption, too dense (prone to Lower extremity nerve lesions
breaks), pancytopenia (low marrow space, extramedullary hematopoiesis), CN impingement Nerve Root Motor Deficit Sensory Deficit Injury
high alk phos Paget's dz (osteitis deformans): increased osteo-clast, then -blast activity causes "mosaic" bone architecture, possibly Obtruator L2-4 thigh adduction medial thigh ant. hip dislocation
viral origin (paramyxo-), chalk-stick fractures, AV shunts (high-output cardiac failure), osteogenic (increased hat size, CN Femoral L2-4 flex thigh, extend leg ant./medial thigh pelvic fracture
impingement, 2° osteosarcoma/fibrosarcoma); also think 1° hyperPTH Common L4-S2 foot eversion/dorsi- anterolateral leg, fibular neck fracture,
osteomalacia/Rickets: defective mineralization, from vitamin D def, usually high PTH, alk phos, low Ca and PO4 peroneal flexion, toe extens'n dorsal foot lateral leg trauma
polyostotic fibrous dysplasia: fibroblasts, collagen, and irregular trabeculae replace bone; McCune-Albright Tibial L4-S2 foot inversion/plan- sole of foot knee trauma
OA: mechanical destruction of articular cartilage, ; sx: pain after use, medial before lateral, no systemic sx (non-inflammatory); can tarflexion, toe flex'n
get subchondral cysts, osteophytes, Heberden's nodes (DIP), Bouchard's nodes (PIP)
OA: mechanical destruction of articular cartilage, ; sx: pain after use, medial before lateral, no systemic sx (non-inflammatory); can
get subchondral cysts, osteophytes, Heberden's nodes (DIP), Bouchard's nodes (PIP) In. gluteal L5-S2 hip extension (stairs) - post. hip dislocation
RA: synovial joints, MCP/PIP pannus formation, subQ nodules (fibrinoid necrosis surrounded by palisading histiocytes), NO DIP S. gluteal L4-S1 Trendelenburg - + polio
INVOLVEMENT, ulnar deviation, subluxation, Baker's cyst; type III hypersensitivity, 80% rheumatoid factor [+] (anti-IgG; anti-CCP=less
sensitive, more specific), HLA-DR4; improves w/ use, systemic sx Bone tumors
seronegative spondyloarthropathies no RF, assn w/ HLA-B27, M>F; psoriatic arthritis: pencil-in-cup, dactylitis (sausage fingers), Benign Epidem. Description
minority of psoriatic pts; ankylosing spondylitis: spine and sacroiliac inflammation, bamboo spine, uveitis, aortic regurg; IBD; Reactive osteochondroma M, <25yo most common benign bone tumor; mature bone w/ cartilage
arthritis: conjunctivitis/uveitis, urethritis, arthritis (exostosis) cap; from metaphyses; transformation rare
Sicca sz: dryness, chronic bronchitis, reflux esophagitis; Sjogren's: dry eyes/mouth, arthritis, anti-RNP (Ro/La) enchondroma M, <25yo intramedullary bone, usually distal extremities
gout: MSU crystalization in joints (negatively birefringent=yellow crystals on parallel), M>F, 90% from under-excretion (diuretics), osteoid osteoma M, <25yo trabeculae of woven bone surrounded by osteoblasts (lytic),
10% overproduction (Lesch-Nyhan, PRPP excess, high cell turnover, von Gierke's Dz); sx: asymmetric, swollen, red, painful, big toe <2cm, usually proximal tibia/femur
MTP (podagra), tophi in external ear, olecranon bursa, Achilles), attacks common after big meal or EtOH binge; acute=NSAIDs, osteoblastoma M, <25yo trabeculae of woven bone surrounded by osteoblasts, >2cm,
colchicine; chronic=allopurinol, uricosurics usually in vertebrae
pseudogout: CaPP crystals (blue when parallel, rhomboid, weakly positively birefringent), large joint (knee) osteoclastoma (giant cell 20-40yo epiphyseal plates of long bones (esp knee); locally aggressive;
infectious arthritis septic: S. aureus, Strep, N. gonorrhea common, monoarticular, migratory, can be synovitis or can also affect tumor) XR='soap bubbles'; spindle-shaped cells
tendons (tenosynovitis); chronic: TB, Lyme osteoma Gardner's new piece of bone growing on another, often in skull
SLE 90% F 14-45, black, die of renal failure and infxn; wire-loop kidney lesions (nephritic), false positive VDRL (from antiphospholipid Malignant Epidem. Description
Ab="Lupus anticoagulant", pro-thrombotic in vivo, causes miscarriages), assn w/ Raynaud's, verrucous endocarditis, hilar LAD; sx: osteosarcoma M, 10-20; 2nd most common 1° malignancy (MM); XR=Codmans
skin (malar, discoid, photosensitivity, mucositis), organ (neuro, renal, serositis, hematologic, arthritis), and lab tests (anti- (osteogenic sarcoma) bad prog. triangle or sunburst pattern, from metaphyses (esp knee);
phospholipid, ANA [sensitive, not specific], anti-Smith [specific, not prognostic], anti-dsDNA [specific, bad prognosis], anti-histone risk: Paget's, bone infarcts, radiation, Rb
[drug-induced])
Ewing's sarcoma M, <15yo extremely aggressive, early mets, chemo-responsive;
sarcoid: immune-mediated non-caseating granulomas, elevated ACE levels, hypergammaglobulinemia, anergy, uveoparotitis, XR=onion-skin; anaplastic small blue cells, t(11;22)
hypercalcemia (macrophage-production of 1α-hydroxylase), Schaumann (giant cell inclusions, seen in granulomas, calcium and chondrosarcoma M, 30-60 may be from osteochondroma; intramedullary
protein, concentric whorls) and asteroid bodies (urchin-like); tx=steroids
connective tissue dzs polymyalgia rheumatica: stiffness/pain in shoulders/hips (NO weakness), malaise, fever, wt loss, labs nl (high Arachidonic acid products
ESR), assn w/ giant cell arteritis; polymyositis: CD8 TC injury to myofibers, symmetric progressive proximal mm weakness PGE1null keeps PDA open; misoprostol=agonist
(shoulders), high CK, aldolase, positive ANA, anti-Jo-1; dermatomyositis: polymyositis + Gottron's papules (extensor surfaces), PGE2 up: pain, uterine tone, temperature; down: vascular tone
mechanic's hands, malar/shawl/heliotrope (racoon eyes) rash, high risk of malignancy, dx=mm biopsy w/ evidence of perifascicular
PGI2 "prostacycline", down: platelet aggregation, vascular tone, uterine tone
inflammation; tx=steroids
TXA2 up: platelet aggregation, vascular tone
scleroderma: excess fibrosis and collagen deposition; CREST=anti-centromere, diffuse=anti-topoisomerase I LTB4 neutrophil chemotaxis
non-infxous derm atopic dermatitis (eczema): pruritic eruption, usually in flexures; ephelis: freckle; psoriasis: acanthosis (spinosum LTC/D/E4 up: smooth m tone, vascular tone/permeability, bronchial tone (-lukast=I)
hyperplasia), parakeratosis (retained nuclei in corneum), hyperkeratosis (thickened corneum), decreased granulosum, Auspitz sign;
albinism: normal # of melanocytes; vitiligo: decreased # of melanocytes; melasma/choasma: hyperpigmentation assc'd w/ Infectious derm
pregnancy/OCP; pemphigus vulgaris: anti-desmosome, reticular IF, acantholysis, Nikolsky's sign (skin separates on stroking); bullous
impetigo honey-crusting, very superficial, highly contageous S. aureus, S. pyogenes
pemphigoid: linear IF stain, eosinophils, spares oral mucosa; dermatitis herpetiformis: IgA deposits; eryhtema multiforme: drugs
cellulitis acute, painful, dermal and subcutaneous tissues S. aureus, S. pyogenes
(sulfa, β-lactams, phenytoin) or infxn (HSV, M. pneumo); lichen planus: sawtooth infiltrate of lymphs at dermal-epidermal jctn,
pruritis, purple, assn w/ hep C; erythema nodosum: panniculitis, ant. shins, assc'd w/ coccidioi-, histoplasma, TB, leprosy, strep, necrotizin deeper tissue injury, causes crepitus (from methane and S. pyogenes or anaerobes
sarcoid; keratoses: actinic=premalignant, seborrheic=benign neoplasm; acanthosis nigricans: hyperinsulin, visceral malign'cy, B3; fasciitis CO2)
pityriasis rosea: herald patch, pine tree
SJS-TEN: anti-psychotic/anti-epilepsy (ethosuxamide, lamotrigine, carbamazepine, phenobarbital,
phenytoin), abx (sulfa, PCN), anti-gout (allopurinol), analgesics (NSAIDs), NNRTIs (efavirens,
photosensitivity: sulfonamides, amiodarone, tetracyclines, SLE, porphyria cutanea tarda, Weil's Sz nevirapine); Nikolski's sign, mucosal involvement
gingival hyperplasia: anti-epileptics (phenytoin), CCBs, cyclosporin, vitamin C deficiency, I-cell dz

Neuro
Breakdown products: (HuMVee DEN) DA to HVA, NE to VMA (vanillylmandelic acid), Epi to metanephrine Spinal cord: inferior is lateral to superior on LCST and STT
UMN lesion: spastic paralysis, clasp-knife spasticity, no atrophy; LMN: fasciculation (twitching), atrophy Tract/Function 1st Order Neuron/Synapse 2nd Order/Synapse/3rd Order
pain/T: C-fibers=unmyelinated, Aδ=lightly myelinated; large myelinated: Meissner (dynamic fine touch, upper dermis), Pacinian Dorsal column/ medial sensory n ending, cell body in 2=decussates in medulla, ascends
(vib/pressure, lower dermis), Merkel's disk (small, around hair follicles, static touch) lemniscus (ascending dorsal root ganglion, ascends contralaterally in medial lemniscus;
spinal cord goes to L1-2, subarachnoid goes to S2, LP usually L3-4/4-5 (level of cauda equina) sensation), from alar ipsilateral dorsal column; S=VPL of thalamus; 3=sensory cortex
plate (embryo) S=ipsilateral nucleus cuneatus or
basal nucleus of Meynert (substantia innominata): ACh-rich, degenerate in Alzheimer's and Huntington's
gracilis (medulla)
nucleus accumbens: GABA synthesis, central in reward, pleasure, addiction, low in anxiety and Huntington's
BBB: infarct destroys endothelial tight jctns, causing vasogenic edema; no BBB in OVLT (organum vasculosum of the lamina Spinothalamic tract sensory n ending (C and Aδ), cell 2=decussates at anterior white
terminalis), area postrema, or neurosecretory areas (pit, eg), all 3 act on hypothalamus (ascending pain and body in dorsal root ganglion, commisure, ascends contralaterally;
hypothalamus supraoptic nuc makes ADH, paraventricular nuc makes oxytocin; lateral area: hunger, inhibited by leptin; temperature) enters spinal cord; S=ipsilateral S=VPL of thalamus; 3=sensory cortex
ventromedial area: satiety (craniopharyngioma can destroy VMA, cause hyperphagia); anterior: cooling, parasympathetic; posterior: gray matter
heating, sympathetic; suprachiasmatic nucleus: circadian rhythm lateral corticospinal tract UMN: cell body in 1° motor cortex, first synapse=cell body of anterior
thalamus VPL=peripheral sensation, VPM=face sensation/taste, to somatosensory cortex; LGN=eyes, MGN=ears (voluntary motion), from descends ipsilaterally in internal horn (spinal cord); LMN: leaves spine,
limbic system cingulate gyrus, hippocampus, fornix, mammillary bodies, septal nuc, for the 5 F's basal plate (embryo) capsule, decussate at pyramid to NMJ (synapse 2)
(caudal medulla), descends
contralaterally
 lateral corticospinal tract UMN: cell body in 1° motor cortex, first synapse=cell body of anterior
(voluntary motion), from descends ipsilaterally in internal horn (spinal cord); LMN: leaves spine,
basal plate (embryo) capsule, decussate at pyramid to NMJ (synapse 2)
(caudal medulla), descends
cerebellum contralateral cortical input via middle peduncle, ipsilateral proprioceptive via inferior peduncle, input=climbing and mossy
contralaterally
fibers, output to stimulate contralateral cortex (Purkinje fibers to deep cerebellar nuclei) via superior peduncle; deep nuclei: ("Ladies
Demand Exceptional Generosity From Men") (Lateral [extremities]) Dentate, Emboliform, Globose, Fastigial (Medial [truncal sympathetics to cell body in hypothalamus, 2=ascend on internal carotid; S=sup.
coordination, fall ipsilaterally]) pupillary dilator m descend in the cord; S=lateral cervical ganglion; 3=int. carotid to
basal ganglia DA from SNc to striatum (caudate=cognitive, putamen=motor, ACh-modulation causes tonic inhibition); direct: D1 horn at T1 long ciliary n (V1)
activates, striatum inhibits GPi/SNr (GABA/substance P), which breaks tonic inhibition of thalamus; indirect: D2 inhibits, breaks
striatum inhibition (GABA, enkephalin) on GPe, GPe inhibits subthalamic nuc, which breaks tonic activation of GPi, which stops Hemorrhages
inhibiting thalamus; both cause motion
epidural will cross falx, tentorium, not suture lines, rapid expansion
myoclonus=hiccup; dystonia=cramp; chorea (sudden) and athetosis (slow) classic for basal ganglia lesion subdural bridging v rupture, elderly/shaken baby, crescent-shaped
precentral gyrus=motor, postcentral=sensory; medial-lateral: foot, leg, arm, hand, face (top to bottom), mouth subarachnoid worst headache of life, ruptured aneurysm, yellow/red spinal tap,
brain lesions reticular activating system (midbrain): reduced arousal and wakefulness (coma); STN: contra-lateral hemiballismus; vasospasm 2-3d later (blood breakdown products, tx=CCB)
hippocampi: anterograde amnesia (no new); paramedian pontine reticular formation: eyes look away from lesion (also responsible
for EOMs in REM); frontal eye fields: eyes look towards lesion Spinal cord lesions
rapid correction of hyponatremia causes central pontine myelinolysis: acute paralysis, dysarthria, dysphagia, diplopia, loss of poliomyelitis mucosa to blood to CNS, destroys anterior horn; nonspecific sx going to
consciousness, axial T1 image shows increased signal in the pons LMN signs; virus recovered from stool or throat
posterior cricoarytenoids: open cords; recurrent laryngeal n injury loses all mm except cricothyroid (vagus) Werdnig-Hoffman AR, degeneration of anterior horns, floppy baby, young death
vertebral/anterior spinal a (medial medullary sz): pyramid (contralateral LE hemiparesis), medial lemniscus (lower contralateral syringomyelia anterior white commissure lesion, usually C8-T1; assn w Chiari
proprioception), hypoglossal fibers (ipsilateral tongue paresis) Tabes dorsalis 3° syphilis, dorsal root and column degen; locomotor/sensory ataxia,
PICA (lateral medullary sz): lateral spinothalamic tract (contralateral pain/T), nucleus ambiguus (efferent X, ipsilateral dysphagia, Charcot joint, shooting pain, no DTRs, positive Romberg
hoarseness, no gag reflex), VIII (vertigo, diplopia, nystagmus, N/V), descending sympathetics (ipsilateral Horner's), V nucleus and B12 neuropathy or demyelination of lateral corticospinal, spinocerebellar, and doral
tract (ipsilateral facial sensation), ICP (ipsilateral ataxia) vitamin E deficiency columns; ataxic gait, hyperreflexia, impaired vib/position
AICA (lateral pontine sz): V and VII (ipsilateral face), VIII (nystagmus), ICP and MCP (ipsilateral dystaxia) Friedreich's ataxia staggering, frequent falls, nystagmus, dysarthria, pes cavus, hammer toes,
posterior cerebral a: contralateral hemianopia w/ macular sparing (supplies occipital cortex) HCM (cause of death), childhood kyphoscoliosis
middle cerebral a: contralateral paralysis (lower half of face down, upper extremities>lowers) & sensory loss (all, usually anterior spinal a. spares dorsal columns and posterolateral tract (of Lissauer); upper
upper>lower), aphasia/L-sided neglect, anosognosia (no knowledge of disease) occlusion thoracic ASA is watershed (a of Ademkiewicz below T8)
anterior cerebral a: leg-foot motor/sensory defects; watershed: severe hypotn, proximal limb weakness ALS both UMN and LMN signs, no sensory, cognitive, or oculomotor defects,
lateral striate: divisions of MCA that supply basal ganglia; posterior limb of internal capsule=pure motor loss can be from superoxide dismutase 1; tx=Riluzole
ant. comm. a: most common site of Circle of Willis aneurism, visual field defects; post. comm. a: III palsy MS: immunosup- autoimmune inflammation and demyelination of CNS, white F, 20-30;
ant. circle=motor, aphasia; post. circle=CN deficits, coma, cerebellar deficits, aphasia/unilateral neglect pression and β-IFN scanning speech, intention tremor, MLF sz (internuclear ophthalmolegia),
aneurysms: assn w/ ADPKD, Ehlers-Danlos, Marfans, age, htn, smoking, blacks; most commonly hemorrhage incontinence, nystagmus, optic neuritis, hemisensory/paresis,
relapsing/remitting; MRI for dx, high IgG in CSF (oligoclonal bands=dxtic),
ischemia: irreversible after 5m, most sensitive=hippocampus, neocortex, cerebellum, watershed; red neurons (12-48h), necrosis +
periventricular plaques (oligodendrocyte loss, reactive gliosis, axon
PMNs (1-3d), macrophages (3-5d), reactive gliosis/vascular prolif (1-2w), glial scar (>2w)
preservation)
stroke: bright on diffusion-weighted MRI (5m-10d), dark on non-contrast CT (24h, bright=hemorrhage, no tPA)
hydrocephalus communicating=decreased absorption; non-communicating=obstruction; NPH: incontinence, ataxia, dementia (wet,
wobbly, wacky), ventricular expansion distorts corona radiata, nl subarachnoid V Brain tumors 50% are mets; presentation due to mass effect (seizure, dementia, etc)
MLF Sz seen in MS; VI nuc projects to ipsilateral abducens and contralateral MLF, which sends fibers to III nuc; so looking to the left, Childhood d Craniopharyngioma supratentorial, benign, confused w/ pit adenoma, calcifications
w/ R MLF damage, R eye doesn't move, L eye has R-beating nystagmus Pilocytic astrocytoma well circumscribed, low grade, cystic + solid, GFAP [+], may be
reflexes Achilles=S1-2; patella=L3-4; biceps=C5-6; triceps=C7-8; Moro: abduct/extend limbs when startled, then draw together, gone supratentorial; Rosenthal fibers: eosinophilic corkscrews
by 3mo; Babinski: dorsiflexion of big toe, fanning of other toes, if after 15mo=UMN lesion Medulloblastoma malignant, primitive neuroectoderm, can compress 4th ventricle
midbrain (III, IV), pons (V-VIII), medulla (IX-XII); lateral=sensory, from alar plate; medial=motor, basal plate (radiosensitive) (hydrocephalus); pseudorosettes or rosettes, small blue cells
nuc of X Solitarius: Sensory; aMbiguus: Motor; dorsal motor: autonomics; PS to lacrimal via VII, pupil via III Ependymoma poor prognosis, usually 4th ventricle (hydrocephalus); blepharoplasts
retinitis: retinal necrosis + edema=atrophic scar; iritis=systemic inflammation; CRAO: acute painless LOV (rods, basal ciliary bodies), pseudorosettes
light enters retina, II, bilateral pretectal nuclei, Edinger-Westphal nuclei, III, bilateral pupil constriction Hemangioblastoma can produce EPO, ass'd w/ vHL; foamy cells, highly vascular
Marcus-Gunn: more constriction on consensual reflex than direct (optic n damage, retinal detachment) Adult d GBM (grade IV most common 1°, cerebral hemispheres, can cross corpus, GFAP [+];
III: ocular mm output is central (affected by vascular dz), surrounded by PS output (affected by compression) astrocytoma) pleomorphic, pseudopalisading, around areas of necrosis
LUQ anopia=Meyer's loop (temporal lobe), LLQ anopia=dorsal optic radiation (parietal lobe); both MCA Meningioma from arachnoid cells, whorled spindle cells, psammoma bodies
brain lesions ring-enhancing: mets, abscess, toxo, AIDS lymphoma; uniformly enhancing: lymphoma, mets, meningioma; Schwannoma commonly on VIII (esp NFM), resectable, S-100 [+]
heterogeneously enhancing: GBM; can cause cingulate (subfalcine) herniation Oligodendroglioma rare, slow growing, frontal lobe; chicken-wire capillary pattern
uncal herniation: ipsilateral Horner (stretch III), contralateral homonomous hemianopia (PCA compression), ipsilateral paresis surrounding fried egg cells, can be calcified
(Kernohan's notch, crus cerebri compression), duret hemorrhages (push brain stem down) Pit adenoma usually PRL, hyper/hypo-pit, bitemporal hemianopia
dementia Alzheimer's, multi-infarct, Pick's dz, Lewy body dementia, CJD, syphilis, HIV, B12def, Wilson's dz Demyelinating dzs (also Charcot-Marie-Tooth)
seizure synchronized, high-f firing; partial: 1 area of brain, usually medial temporal lobe, can generalize, can be simple PML oligodendrocyte destruction, assc'd w/ JC virus, 2-4% of AIDS, rapidly fatal
(consciousness intact) or complex; generalized: absence (petit mal, no post-ictal confusion), myo-clonic, tonic-clonic (grand mal), metachromic AR lysosomal storage dz, arylsulfatase A def, buildup of sulfatides,
tonic, or atonic; epilepsy: recurrent seizures (non-febrile); in kids: genetic, febrile, trauma, congenital, metabolic; adults: tumor, leukodystrophy impaired production of myelin sheath
trauma, stroke, infxn; old: stroke, tumor, trauma, metabolic, infxn; drugs: INH, bupropion, imipenem/cilastatin
acute disseminated (post-infxous) perivenular inflammation and demyelination, after infxn (VZV,
encephalomyelitis measles) or vax (rabies, smallpox)
headache migrane: unilateral, 4-72h, pulsating, N, photo-/phono-phobia, from irritation of V and release of substance P, CGRP,
vasoactive peptides (vasodilators); tension: bilateral, >30m, steady pain, no aura/photo-/phono-phobia; cluster: lacrimation,
Horner's, rhinorrhea, M>>F, tx=sumatriptan or hyperbaric O2
headache migrane: unilateral, 4-72h, pulsating, N, photo-/phono-phobia, from irritation of V and release of substance P, CGRP,
vasoactive peptides (vasodilators); tension: bilateral, >30m, steady pain, no aura/photo-/phono-phobia; cluster: lacrimation, vertigo peripheral: more common, positional testing=delayed horizontal nystagmus; central: brain
Horner's, rhinorrhea, M>>F, tx=sumatriptan or hyperbaric O2 stem/cerebellum, testing=immediate nystagmus, any direction

Psych (dzd=disorder)
diseases/NTs anxiety=SONIGO; depression=SODONO; Parkinson's: ODISIA; Schizophrenia: ID; Alzheimer's: OA Ego defenses
hospitalism/anaclitic depression: infant depression from to separation, withdrawn/unresponsive baby Pathologic conversion manifestation as physical sx (grief causes "blindness", hysteria)
childhood dzs ADHD: normal intelligence, commonly continue into adulthood, low frontal lobe V; conduct dzd: antisocial personality denial, delusional/extreme projection, distortion, splitting (all good/all bad)
disorder <18yo; oppositional defiant dzd: no serious violations; Tourette's: assn w/ OCD, movements + tics; separation anxiety dzd: Immature projection impulses attributed to external source
may have factitious physical sx fixation remaining partially at a more childish level
Autism: language/social impairment; Asperger's: social impairment, no cognitive/verbal defects; Rett's: F>M, XL, regression, loss of acting out, fantasy, idealization, identification (modeling after power, not admiration)
development/verbal/motor abilities, hand-wringing; childhood disintegrative dzd: multiple areas of regression after 2y of normal Neurotic displacement feelings transferred to safer outlet, scapegoating
development, M>F, usually presents between 3-4yo regression going back to childish level
delerium: acute onset waxing/waning consciousness, visual hallucinations, illusions, abnormal EEG; dementia: gradual decreased dissociation, rationalization (excuses), isolation of affect, repression, rxn formation
cognition, no psychosis, normal EEG, depression=pseudodementia Mature suppression voluntary withholding from conscious awareness
hallucination: no stim; illusion: misinterpretat'n of stim; delusion: false belief; loose ass'n: disordered thought sublimation unacceptable impulses in an acceptable way (aggression/boxer)
hallucinations audio=schizophrenia, olfactory=aura, tactile=DT/cocaine; hypno-gog-/-pomp-ic: falling/get up humor, altruism
schizophrenia genetic>environmental, 1.5% lifetime prevalence; pick 2: delusion, hallucination, loose assns, disorganized/catatonic
behavior, negative sx (flat affect, social withdrawal, lack of speech or thought); low dendritic branching; brief psychotic dzd (stress Personality dzds (weird, wild, worried)
related)<1mo<schizophreniform<6mo<schizophrenia; suicide Cluster A: odd/eccentric, no meaningful relationships; assc'd w/ schizophrenia
schizoaffective dzd: >2w of stable mood w psychotic sx + a major depressive, manic, or mixed episode Paranoid pervasive distrust, projection
dissociative identity dzd: multiple personalities, ass'd w/ sexual abuse; depersonalization dzd: persistent feeling of Schizoid voluntary social withdrawal, limited emotional expression
detachment/estrangement; dissociative fugue: abrupt change in geographic location w/ amnesia Schizotypal + eccentric beliefs/appearance, magical thinking, awkward
bipolar 1 manic (bipolar I) or hypomanic (II) episode, depression always occurs eventually; high suicide risk Cluster B: dramatic, emotional; associated w/ mood disorders and substance abuse
dysthymia: mild depression, >2yr; cyclothymic dzd: + hypomania, mild bipolar>2yr Antisocial disregard for rights of others, criminal, M>F >18, (conduct dzd)
manic >1wk, pick 3: distractable, irresponsible (hedonism), grandiose, flight of ideas, agitation (high activity level), sleeplessness (no Borderline unstable, impulsive, self-mutilating, emptiness, F>M; splitting
need), talkativeness (pressured speech); hypomanic: no impairment or psychoses Histrionic excessively emotional, attention seeking, overly sexual
depression self-limited, episode lasts 6-12mo, lifetime prevalence: F=20%, M=10%; 2+ wk of pick 5: sleep disturbance (early morning Narcissistic grandiose, sense of entitlement, lacks empathy
awakening most important), loss of interest (anhedonia, necessary), worthless/ guilt, low energy, low concentration, change in Cluster C: anxious, fearful; associated w/ anxiety dzds
appetite, psychomotor sx, suicidal ideation, depressed mood; MDD: 2 episodes w/ 2mo sx-free; atypical depression: hypersomnia, Avoidant hypersensitivity to rejection, inhibited, desires relationships
overeating, mood reactivity; postpartum depression: 15% incidence, depressed affect, anxiety, poor concentration, lasts 2w-2mo;
OCPD perfectionist, ego syntonic (OCD=dystonic, ass'd w Tourette's)
refractory=ECT tx
Dependent submissive, clingy, low self confidence
suicide sex (M), age (teen/elderly), depression, previous attempt, EtOH/drugs, rational thinking, sickness (3+ rxs or medical illness),
organized plan, no spouse/lack of social support; F try more, M succeed more Psych txs
panic dzd recurrent, intense fear, peaks in 10m, pick 4: palpitations, parasthesias, abd distress, N, fear of dying/losing control, light- EtOH withdrawal/cocaine OD BDZ
headed, chest pain, chills, choking, sweating, shaking, SOB, disconnectedness ADHD methylphenidate, amphetamines (dexedrine)
GAD: >6mo, uncontrolled anxiety, sleep disturbance, fatigue, GI sx, difficulty concentrating; adjustment dzd: GAD with specific schizophrenia antipsychotics
stressor, usually <6mo; PTSD: reexperiencing traumatic event: acute stress dzd<1mo<PTSD Tourette's antipsychotics (esp haloperidol)
conscious faking: malingering=2° gain (miss work, get drugs), avoid tx; factitious dzd: to assume sick role (1° gain), take invasive txs, depression SSRIs, SNRIs, TCAs
Munchausen (chronic, predominantly physical sx, by proxy=child abuse) atypical depression MAOIs, SSRIs
somatoform dzd physical sx, no identifiable cause, unconscious, F>M; somatization: multiple organ system complaints; conversion: pt depression + insomnia Mirtazapine
is aware but indifferent to sx ("la belle indifference"); hypochondria: fear of having serious dz despite tests; body dysmorphic dzd: bipolar dzd stabilizers (valproate, Li, carbamazepine), atypicals
minor/imagined defect, repeated cosmetic surgery; pain dzd anorexia/bulemia SSRIs
substances dependence: pick 3 in 1yr: tolerance, withdrawal, more than desired, desire to cut down, too much energy spent getting, anxiety BDZ, buspirone, SSRIs
using, or recovering from, important activities reduced, continued use in spite of insight; abuse: failure to fulfill major obligations, OCD SSRIs, TCAs, BDZs
physically hazardous situations, legal problems, CUIS of insight PTSD SSRIs
DT: ANS hyperactivity (hi HR, tremor, anxiety, seizure), then psychosis (hallucination, delusion), then confusion social phobia SSRIs

Behavioral Science
bias selection: nonrandom group assignment; late-look: inappropriate time for observation; lead-time: early detection confused w/ Early developmental milestones
increased survival; Pygmalion effect: researcher's belief in efficacy changes outcome; Hawthorne effect: group studied changes Infant <3mo rooting reflex orients to voice
behavior; sampling: nonrepresentative to pop. (not generalizable) 3-6mo holds head up, Moro reflex disappears social smile
prevention 1°: prevent occurance (vax); 2°: early detection (screening); 3°: reduce disability from dz (tx) 6-9mo sits alone, crawls stranger anxiety
reportable dzs: Hep, AIDS, gonorrhea, syphilis, TB, MMR, salmonella, shigella, VZV; HIV varies by state 12mo walks, Babinski disappears separation anxiety, few words
Medicare >65, ESRD, etc; A=inpatient, hospitals, hospice, home health; B=outpatient, drs services, PT/OT; C= combo; D=rxs; Toddler 1-2yr climb stairs, stack 3-6 blocks object permanence, 200 words
Medicaid: health assistance for very low income 2-3yr stack 6-9 blocks, toilet training gender identity, parallel play
Advance directives living will: txs refusal (DNR); durable power of attorney: appointing a medical surrogate Preschool 3-4yr rides tricycle, copies line drawing 900 words, complete sentences
APGAR (1): appearance (trunk pink), pulse (<100), grimace (2=grimace + cough), activity (some), resp (irregular) 4yr cooperative play, imaginary friends, grooms self, buttons and zips
sleep spend most time in stage 2 (bruxisms); stage 3-4 (delta)=enuresis, night terror, sleep walking; raphe nuc (5HT) key in initiating; Tanner 1=childhood; 2=adrenarche (pubic hair, breasts); 3=hair darkens, curls, penis longer; 4=penis
NE reduces REM (depression, decreased latency, increased total, repeated awakening); narcolepsy: starts with REM sleep, can have wider, scrotum darkens, raised areolae; 5=adult, areolae not raised
cataplexy (fainting goats) or hypna-gog/pomp-ic hallucinations circadian rhythm driven by suprachiasmatic nuc of hypothalamus, regulated by light

Renal
60% water by wt (40L), 2/3 intracellular, 1/3 ECF (inulin, 1/5 plasma [radiolabeled albumin], 4/5 interstitial) Electrolyte disturbances
glomerular filtration: fenestrated capillaries (size), podocyte foot processes, fused BM w/ heparin SO4 (charge) Low High
Cx=VUx/Px; GFR=Cinulin<CCr (CCr=slight overestimation); ERPF=CPAH (underestimates RPF by 10%); RBF=RPF/(1-Hct) Na disorientation, stupor, coma irritability, delirium, coma
filtered load=GFR(Px); FF=GFR/RPF (high: efferent constriction, low Pprotein; low: ureter constriction, high Pprotein) K EKG changes (U-waves, flat T's), EKG changes (peaked T's, wide QRS), arrhythmias
arrhythmia, paralysis
PCT basal Na/K ATPase creates low [Na]i, powers everything: symports (glucose, PO4 [PTH inhibits], AAs [3]), antiports (H from
intracellular CA, combines w luminal bicarb, brush border CA catalyzes back to resorbed CO2, bicarb resorbed basolaterally, [Na/K Ca tetany, NM irritability delerium, renal stones, abd pain, stupor
pump stimulated by AII, contraction alk]), Cl resorbed paracellular, ammoniagenesis (gln to glu to αKG [broken down & absorbed as Mg NM irritability, arrhythmias delerium, low DTRs, cardiopulm arrest
2bicarb] each generates an ammonium ion) PO4 (IP) osteomalacia renal stones, metastatic calcifications
TF/P graph Cl and urea more quickly absorbed in distal 2/3 of PCT, so hyperbolic up and right; phosphate and bicarb mirror below
y=1; glucose=160-200, glucosuria begins, 350, all transporters fully saturated Nephrotic lost heparin sulfate causes massive proteinuria (>3.5g/d, thromboemboli, hyperlipidemia,
ALOH basal: Na/K ATPase, passive K and Cl chs; NKCC (Na/K/2Cl symport), paracellular Mg and Ca resorption edema), fatty casts, can lose Igs (infxn risk); FSGS: most common GN in adults and HIV pts; Minimal
DCT basal: Na/K ATPase, Na/Ca antiport (induced by PTH); luminal Na/Cl symport (thiazide) and Ca ch change dz: aka lipoid nephrosis, in kids, triggered by recent infxn, tx=steroids, LM=no change;
amyloid; DMGN: (type III) drugs, infxn, SLE, tumors, thickened GBM/capillaries, EM="spike-and-
CT principal cell: basal V2R (ADH) inserts aquaporins luminally; ENaC (aldo induced) absorbs Na in exchange for K and H; intercalated
dome"; MPGN: can be nephritic too, type 1="tram track" (HBV/HCV related), type 2=dense deposits
cells: α=secretes H (K/H antiport, H ATPase, basal HCO3/Cl antiport), β=backward α
(EM, assc'd w/ C3 nephritic factor); diabetic glomerulonephropathy: non-enzymatic glycosylation
RAS renin (from JG): low BP (JG cells), low Na delivery (MD), high β1; ACE: converts AI, degrades bradykinin (vasodilator); AII: vascular (NEG) of GBM causes thickening and increased permeability, NEG of efferent increases GFR causing
smooth mm constriction (BP up), constricts efferent arteriole (raise FF to preserve GFR in low RBF), aldo secretion (increases ENaC, mesangial expansion, nodular glomerulosclerosis (KW lesions)
Na/K, and Kch in principal cells, intercalated H ch [all retain Na, excrete K and H]), ADH secretion, upregulate PCT Na/H antiport
(contraction alk), ups thirst, limits baroR-mediated reflex bradycardia; nromally: aldo regulates V, ADH regulates Osm; PGE2: dilates
afferents
Nephritic inflammation of glomeruli causes (PHAROH) proteinuria (<3.5g), hematuria, azotemia, RBC
ANP: high atrial P, increases GFR and Na filtration, no compensatory distal Na or water resorption casts, oliguria, htn; IgA nephropathy (Berger's dz): increased IgA synth, often presents after URI or
exocrine EPO: secreted by interstitial fibroblasts after peritubular capillary hypoxia, ectopic EPO secretion causes inappropriate acute gastroenteritis, assc'd w/ Henoch-Schonlein; acute poststrep (postinfxous): in kids, glomeruli
absolute polycythemia: HCC, RCC, Wilm's, hydronephrosis; 1,25-D: made by PCT enlarged/hypercellular, "lumpy-bumpy", periorbital/peripheral edema, resolves spontaneously;
rapidly progressive (crescent) GN: crescents of fibrin, plasma proteins, parietal cells, monocytes, &
respiratory compensation for MAc: PCO2=1.5(HCO3)+8; for MAlk: PCO2 up 0.7 for every +1 HCO3
macrophages, poor prognosis, from Goodpastures, Wegeners, or microscopic polyangiitis; Alport's:
acidoses/alkaloses RAc: hypoventilation; RAlk: hyperventilation or aspirin ingestion (early); MAlk: vomiting, diuretics (contraction), split BM; diffuse proliferative: from SLE or MPGN, "wire-looping" of capillaries
antacids, hyperaldo; MAc, check the AG (anion gap=Na-(Cl+bicarb), nl=8-12); nAGMAc (hyperCl): diarrhea (bicarb loss), glue sniffing,
RTA; hAGMAc (extra anions): drugs (Fe OD, INH, paraldehyde, metformin, salicylates), ingestion (MeOH [formate], ethylene glycol
[oxalate]), metabolic (uremia, DKA, lactic)
Immune deposits
RTAs T1 (distal): α intercalated cell def, inability to secrete H, causes hypokalemia, risk for Ca-stones; T2 (proximal): can be from Sub-epithelial Sub-endothelial Mesangial
Fanconi's/expired tetracyclines, PCT bicarb resorption def, hypokalemia, hypoPO4mic rickets (XLD, excess PO4 excretion); T4 Membranous GN (DMGN) Cryoglobulinemia Berger's Dz (IgA nephropathy)
(hypoaldo): hyperK causes cellular H/K antiport (make Kout normal causes intracellular alkalosis), inhibits ammoniagenesis (low urine Postinfectious GN MPGN
pH & buffering capacity), nAGMAc (mild) Immunofluorescence Pattern
casts hyaline: nothing; RBC: GN, ischemia, malignant htn; WBC: tubulointerstitial inflammation, acute pyelo, transplant rejection; Granular Linear Light and Dark Areas
granular: ATN; waxy: advanced renal dz/CRF; Bence Jones protein: multiple myeloma Membranous GN Goodpastures Berger's Dz (IgA nephropathy)
RCC: renal tubular cells become polygonal clear cells; vHL, smoking, and obesity; hematuria, mass, flank pain, fever, polycythemia Postinfectious GN
(other neoplastics too: ACTH, PTHrP, PRL); spreads hematogenously (IVC) to bone/lung MPGN
Wilm's tumor (nephroblastoma): contains embryonic glomerular structures; huge mass, hematuria, WT1 gene (tumor suppressor, Other Characteristics
11p) deletion; can be part of WAGR complex (Aniridia, GU malformation, Retardation) Diffuse glomerular proliferation Low Complement
transitional CC: painless hematuria=bladder cancer; phenacetin, smoking, aniline dye, cyclophosphamide Postinfectious GN Postinfectious GN
pyelo acute: affects cortex, spares glomeruli/vessels; fever, CVA tenderness, N/V, WBC casts; chronic: coarse corticomedullary MPGN MPGN
scarring, blunted calyx, dilated/atrophic tubules contain eosinophil casts (thyroidization) SLE Cryoglobulinemia
interstitial nephritis: drug induced, usually 1-2wk after rx (diuretics, NSAIDs, PCNs [esp methacillin], rifampin, sulfonamides);
haptens; hematuria, pyuria (eos), azotemia, fever, rash, CVA tenderness, normal tubules Kidney stones
diffuse cortical necrosis: cortical infarct of both kidneys, usually DIC (esp pregnancy) and vasospasm Ca CaOx most common, can be from ethylene glycol or vit C abuse; hyperPTH
ATN: most common cause of ARF in hospital, reversible, fatal if untxed, oliguric phase most dangerous, granular (muddy brown) NH4MgPO4 infxn w/ urease bugs (Proteus, eg), can be staghorn, worse w/ alkaluria
casts; ass'd w/ ischemia (shock/sepsis), crush injuries (myoglobinuria), toxins Urate radiolucent, strong assn w/ hyperuricemia (gout, B3), high cell turnover
papillary necrosis: gross hematuria/proteinuria; assn w DM, acute pyelo, chronic phenacetin use, HbS Cystine hexagonal crystals, usually 2° to cystinuria, tx=alkalinize urine
ARF abrupt decline in renal function w/ high Cr and BUN over days; prerenal: low RBF and GFR (hypotn); renal: usually ATN, less ARF (acute kidney injury)
commonly acute GN (RPGN, eg), patchy necrosis causes obstruction and backflow across tubule, low GFR, epithelial/granular casts, U(Osm) U(Na) FeNa Serum BUN/Cr Epidemiology
impaired resorption; postrenal: bilateral obstruction (BPH, eg) Prerenal >500 <10 <1% >20 community
renal failure: Na/water retention, hyperK, MAc, uremia (can cause N/anorexia, pericarditis, asterixis, platelet dysfunction, Renal <350 >20 >2% <15 hospital
encephalopathy), anemia, renal osteodystrophy (2° hyperPTH), dyslipidemia (esp hyperTGemia) Postrenal <350 >40 >4% >15 BPH/cancer mets
cysts ADPKD (assn w/ polycystic liver dz, berry aneurysms, MVP, htn), ARPKD (infantile, assn w/ hepatic fibrosis, portal htn, Potter's), dialysis, simple, medullary (can lead to fibrosis/insufficiency, atrophic kidney)
 Reproductive
ligaments suspensory L of ovary: ovary to wall, houses ovarian vessels; L of ovary: ovary to uterus, no vessels; round L: uterus to labia Placental pregnancy complications
majora; cardinal L: cervix to pelvis, houses uterine vessels; all within broad L Abruptio 3rd trimester, painful bleeding; premature detachment of placenta; fetal death, can
pudendal nerve block given at ischial spine; ureters go under uterine a/ductus deferens (retroperitoneal) placenta cause DIC; risk: smoking, htn, cocaine use
ovary=simple cuboidal, uterus=simple columnar, pseudostratified, tubular glands; prostate=* Placenta any trimester, painless bleeding; placental attachment to lower uterine segment, may
NE causes increased intracellular Ca, smooth mm contraction, vasoconstriction, and antierectile (NO=pro-) previa occlude os; risk: multiparity or prior C-section
Sertoli cells: FSHR (secrete inhibin and ABP [high local T levels]), secrete AMH (sex organ development), maintain blood-testis Placenta after delivery, massive bleed; defective decidua (placental attachment to
barrier, support spermatozoa, regulate spermatogenesis; Leydig cells: LHR, secrete T accreta myometrium), no separation; risk: prior C-section, placenta previa
spermatogenesis spermatogonium (maintain germ pool) make 1° spermatocytes, 2° spermatocytes, spermatid; spermiogenesis Retained after delivery, may cause hemorrhage
spermatid to spermatozoa; acrosome=Golgi, flagellum=centriole, middle piece=mitochondria endometriosis: ectopic endometrial glands, nonneoplastic, cyclic bleeding/pain or chocolate cysts,
T induces internal structure differentiation from Wolffian duct; DHT: external structures + prostate (UG sinus) usually in ovary/peritoneum; adenomyosis: w/i myometrium
M genitalia spermatic cord: 3aa (cremaster, testicular, to ductus deferens), 3nn (genital branch of genito-femoral, sympathetics), 3 endometrial hyperplasia (excess E, sx=postmenopausal bleeding; risk=anovulatory cycles, HRT,
fascial layers (cremasteric [int. oblique], external [ext. obl.]/internal [transversalis] spermatic), 3 others (pampiniform plexus, vas, PCOS, granulosa cell tumor) biggest risk for endometrial carcinoma
lymphatics); scrotal layers: (some damn englishman called it the testes) skin, dartos, external spermatic fascia, cremaster m, internal, endometrial carcinoma: most common gynecologic malignancy; sx=vaginal bleeding; risk=obesity,
tunica vaginalis/albuginea DM, htn, nulliparity, late menopause, PCOS, endometrial hyperplasia
estrogendevelopment of F 2° sex characteristics, growth of follicle, endometrial prolif, increased myometrial excitability, upregulation myometrial tumors leiomyoma=fibroid, most common tumor in F, usually multiple, well-
of Rs (E, P, LH), stimulates PRL secretion but blocks its effect at breast, increase in transport proteins (SHBG, TBG), increase HDL, demarcated, benign, E-sensitive (grows w/ pregnancy), 30yo; asxatic, abnormal uterine bleeding, Fe
lower LDL; LH activates desmolase in theca cells (chlsl to androstenedione), FSH activates aromatase in granulosa cell def anemia, miscarriage; whorled pattern of smooth mm bundles; leiomyosarcoma: irregular shape,
(androstenedione to E); during pregnancy, estradiol (most potent) and estrone (less) up 50x, estriol (least potent) up 1000x (indicates necrosis, recur, aggressive, usually middle-aged
fetal well-being)
anovulation PCOS, obesity, HPO abnormalities, POF (menopause before 40, follicular atresia),
progesterone stimulates endometrial glandular secretions, spiral a development, maintains pregnancy, decreases myometrial hyperPRL, thyroid/eating dzd, Cushing's, adrenal insufficiency
excitability, makes thick cervical mucous to prevent sperm into uterus, ups body T, uterine tone relaxation (prevents contractions), PCOS: high LH causes anovulation, hyperandrogenism (androstenedione from theca cells); low FSH,
decrease ER expressivity; at birth, drop in P causes lactation high T, enlarged bilateral cystic ovaries, amenorrhea, hirsutism, and obesity; assn w insulin
cycle day0=basal endometrial layer, proliferative phase for 2 wk (FSH, follicular growth fastest in wk2), day 14=(LH) ovulation, corpus resistance; higher risk of endometrial cancer
luteum secretes progesterone; day21: no implantation, corpus regresses, menses cysts follicular cyst=unruptured Graffian follicle; corpus luteum cyst=hemorrhage into persistent CL,
polymenorrhea<21d<nl<35d<oligomenorrhea; metrorrhagia=irregular bleeding; menorrhagia=heavy bleeding regresses spontaneously; theca-lutein cyst=bilateral/multiple, from Gn stimulation, assn w chorioca
oogenesis (oogonium to 1° oocytes) meiosis I starts in fetal life, arrested in prophase until ovulation (2° oocyte), meiosis II arrested in and moles; chocolate cysts=endometriosis
metaphase until fertilization (ovum) Ovarian tumors: Germ cell (most common in adolescents)
fertilization usually 1d after ovulation at ampulla of fallopian tube (middle 1/3); suckling maintains lactation via increased n Teratoma 90% of ovarian germ cell tumors; cells from 2-3 germ layers;
stimulation (increases oxytocin [milk letdown] and PRL [lower reproductive function]) mature=benign, immature=aggressive; struma ovarii=hyperT3
Klinefelter's (XXY) disgenesis of seminiferous tubules (low inhibin, high FSH, low T, high LH, high E, testicular atrophy), eunuchoid Dysgerminoma malignant, eq to but rarer than male seminoma; uniform sheets of cells,
body, tall, long extremities, gynecomastia, female hair distribution, can have develop-mental delay; Barr body, common cause of large nuclei; tumor marker: hCG, LDH
hypogonad; XYY: phenotypically normal, tall, bad acne, antisocial Choriocarcinoma can develop in pregnancy in mother or baby; hyperchromatic, large
Turner's (XO) short stature, ovarian dysgenesis (normal fetal ovarian development, bt follicles lost by 2yo, "streak ovary"), shield (hematogen. spread) nuclei; increase frequency of theca-lutein cysts; hCG
M and F
chest, bicuspid aortic valve, neck webbing (cystic hygroma), preductal coarctation of aorta, aortic dissection, most common cause of Yolk sac (endodermal in testes, ovaries, or sacrococcygeal area of kids; yellow, friable, solid
1° amenorrhea (high FSH and LH), no Barr body sinus) masses; 50% have Schiller Duval bodies; AFP
pseudohermaphroditism external gender doesn’t match internal genitalia; XX=virilization, excess androgens (11βOHase def, Ovarian tumors: Non-germ cell (CA-125=general ovarian cancer marker)
exogenous); XY=usually androgen insensitivity sz (normal-appearing F, rudimentary vagina, testes found in labia, removed to prevent Serous cystadenoma most common benign ovarian tumor, fallopian-tube epithelium
malignancy); true hermaphrodite: both ovary and testis, very rare Serous cystadenoca 50% of all ovarian tumors; malignant, frequently bilateral; BRCA-1, HNPCC
5αRase def: AR, limited to XY, ambiguous genitalia until puberty, then masculinization; LH may be high (FHx is most important risk factor)
hydatidiform mole cystic swelling of chroinic villi, prolif of trophoblast (chorionic epithelium), "cluster of grapes", snowstorm on Mucins cystadenoma mulitlocular cyst, benign, intestine-like tissue
sonogram, present w/ abnormal vaginal bleeding, tx=D/C and MTX, monitor βhCG; complete: 46,XX (or XY), 2 sperm + an empty egg, Mucins cystadenoca pseudomyxoma peritonei: intraperitoneal mucus accumulation
VERY HIGH βhCG, increased uterine size (risk of rupture), 2% convert to chorioca, 15% get malignant trophoblastic dz, no fetal parts; Brenner tumor benign, looks like bladder
partial: 69XXY, moderately high hCG, 2 sperm + 1 egg, low risks of malignancy, contains fetal parts
Fibromas bundles of spindle-shaped fibroblasts, part of Meigs' Sz
Granulosa cell tumor secretes E (precocious puberty, endometrial hyperplasia/ca), abnormal
common causes of recurrent miscarraige 1st wk=low P levels (no response to hCG); 1st trimester=chromosomal abnormality uterine bleeding Call-Exner bodies (red, exracellular)
(robertsonian translocation); 2nd trimester=bicornate uterus (paramesonephric fusion failure) Krukenberg tumor GI malignancy that mets to both ovaries, mucin-secreting
preeclampsia htn, proteinuria, edema, must be >20wk pregnant, ass'd w/ htn, DM, autoimmune dzs, chronic renal dz; impaired vaginal sarcoma botryoides (rhabdo variant): <4yo, spindle-shaped, desmin-positive
vasodilation of spiral aa causes placental ischemia, causing increased vascular tone; other sx: headache, blurred vision, abd pain, Testicular tumors: Germ cell (95% of testicular tumors, can be mixed, all malignant)
altered mentation, hyperreflexia, hyperuricemia, low platelets; tx=delivery, bed rest, salt restriction, MgSO4, diazepam Seminoma painless, homogenous test, enlargement; most common test. tumor,
25yo, radiosensitive, late mets; lobules, clear cytoplasm
HELLP sz: hemolysis, elevated LFTs, low platelets, VERY BAD (can cause cerebral hemorrhage and ARDS) Embryonal ca painful, worse prognosis, often glandular/papillary, can differentiate to
maternal DM: caudal regression sz (anal atresia/sirenomelia), macrosomia, NRDS, postnatal hypoglycemia other tumors; can have AFP/hCG tumor markers
ectopic pregnancy: usually in fallopian tubes, high hCG w/ sudden lower abd pain, dx=US; risk=hx of infertility, salpingitis/PID, Teratoma mature teratoma is most likely malignant
ruptured appendix, prior tubal surgery, prior ectopic Testicular tumors: Non-germ cell (5%, mostly benign)
fibrocystic dz most common cause of breast lumps 25-menopause, premenstrual pain, fluctuates in size, no increased risk for cancer, Leydig cell contains Reinke crystals; gynecomastia, precocious puberty
multiple/bilateral; fibrosis: hyperplasia of stroma; cystic: ductal dilation, blue dome; sclerosing adenosis: increased acini and
intralobular fibrosis, calcifications common; epithelial hyperplasia: increase in cell layers in terminal duct lobule, >30yo, if atypical
cells=increased risk for ca
fibrocystic dz most common cause of breast lumps 25-menopause, premenstrual pain, fluctuates in size, no increased risk for cancer,
multiple/bilateral; fibrosis: hyperplasia of stroma; cystic: ductal dilation, blue dome; sclerosing adenosis: increased acini and Sertoli cell androblastoma from sex cord stroma
intralobular fibrosis, calcifications common; epithelial hyperplasia: increase in cell layers in terminal duct lobule, >30yo, if atypical Testicular lymphoma common in older men
cells=increased risk for ca
Benign breast tumors
other common conditions acute mastitis: abscess, S. aureus most common, usually during breast feeding; fat necrosis: painless, from Fibroadenoma most common tumor <35yo; small, mobile, firm, sharp edges; responds to
injury (usually not reported/remembered); gynecomastia: hyperestrogenism (age, cirrhosis, testicular tumor), XXY, rxs (E, estrogen (pregnancy, menstruation); not pre-malig.
psychoactive drugs, dig, cimetidine, ketoconazole, spironolactone) Intraduct papilloma serous or bloody nipple discharge, slight increased risk for ca
malignant breast tumors: common post-menopause, from mammary duct epithelium or lobular glands; over-expression of erb-B2 Phyllodes tumor most common in 60s; big, leaf-like projections; may transform
(EGF-R) common; most important prognostic factor=axillary LN involvement; risk factors: high E, older age at first live birth, obesity Malignant breast tumors
(adipose tissue has aromatase, so increases E exposure) Invasive ductal most common, worst; firm, fibrous, sharp margins, small cells
prostate -itis: dysuria, frequency, urgency, low back pain (acute=bacterial, chronic is usually abacterial); BPH: hyperplasia of Invasive lobular orderly rows of cells, often multiple and bilateral
lateral/middle lobes, dysuria, frequency, nocturia, hesitancy, high PSA; adenoca: posterior lobe usually, dx by DRE, high PSA, low Medullary fleshy, cellular, lymphocyte infiltrate, good prognosis
fraction of free PSA, osteoblastic mets to bone (high alk phos), PAP Comedocarcinoma ductal, caseous necrosis, DCIS subtype
penis CIS Bowen's dz: gray crusty plaque, 50s, progresses to SqCC <10%; erythroplasia of Queyrat: red velvety plaque; Bowenoid Inflammatory dermal lymphatic invasion by ca and block (Peau d'orange)
papulosis: multiple papules, younger, usually noninvasive Paget's dz eczematous nipple, large cells w/ clear halo, underlying tumor
varicocele: dilated vv, can cause infertility, bag of worms, cant be transilluminated (others can); hydrocele: increased fluid 2° to incomplete fusion of processus vaginalis; spermatocele: dilated epididymal duct
Respiratory
type II pneumocytes: secrete surfactant (lecithin=dipalmitoyl phophatidylcholine, constitutive excretions), proliferate during lung Lung volumes
damage, lamellar bodies; lecithin/sphingomyelin>2.0 in amniotic fluid=lung maturity inspiratory capacity=IRV + TV
clara: nonciliated columnar, secretory granules (component of surfactant, degrades toxins), reserve FEV1=after full inspiration, V forcibly expired in
aspiration: upright=lower portion of RLL, supine=superior portion of RLL; A to B (artery to bronchus): RALS the first second; low in restrictive, very low in
external intercostals used for active inpiration, fibers point down; other active inspiratory mm: scalene, SCM obstructive
surfactant: raises compliance (change in V/P, reciprocal of elastance [lowered]), deficient in neonatal RDS FVC=after full inspiration, total V forcibly
Law of Laplace: P favoring collapse=2(surface tension)/r (so low surfactant or low radius tends to collapse) expired; low in obstructive, very low in
lung produces ACE (inactivates bradykinin) and kallikrein (activates); ACEI causes increased lung bradykinin restrictive
dead space=TV(PaCO2-PeCO2)/PaCO2; biggest contributor in healthy ppl is apices (fewer deeper breaths better) FEV1/FVC=hallmarks: obstructive<70%,
Hb: taut has low O2 affinity, favored by exercise (increased T, [H], pCO2, altitude, 2,3DPG); 2,3DPG: byproduct of glycolysis, marker restrictive>80%
of cell activity, binds less avidly to HbF; P50(nl)=26; 75% sat=hypoxemia, 50%=cyanosis
methemoglobin: oxidized form (Fe3+), very high affinity for CN, so in CN poisoning, nitrites (amyl nitrite) given to oxidize Fe to bind O2 in the blood Equation Nl value Changed by
CN (prevents cytochrome oxidase dysfunction); thiosulfate then given to bind and excrete renally; can also be formed as a side effect O2 content BC + dissolved O2 20.4g/mL any change in BC or DO2
of dapsone; dark blue/brown color binding capacity 1.34 * Hb * % sat 20.1g/mL down: anemia
carboxyHb: bound to CO, lower binding capacity, L-shift (stays in relaxed form), ETC inhibitor, hyperbaric O2 dissolved O2 PO2 * 0.3% 0.3g/mL up: 100% O2
diffusion-limited: CO, O2 in emphysema and fibrosis (doesn't equilibrate by end of capillary); everything else perfusion limited
(equilibrates early on); emphysema lowers SA, fibrosis increases thickness Lung cancer
pulmonary htn: >25mmHg at rest or >35 during exercise, causes atherosclerosis, medial hypertrophy, intimal fibrosis; 1°=inactivating Type Location Characteristics
mutation of BMPR2 (normally inhibits smooth m prolif, poor prognosis); 2°=(COPD, mitral stenosis, emboli, autoimmune (diffuse SqCC (smoking) central cavitation, PTHrP; keratin pearls, intercell'ar bridging
scleroderma), L to R shunt, apnea), causes cor pulmonale Small CC central very aggressive; ACTH, ADH, Lambert-Eaton, chemo-
alveolar gas eq: PAO2=PIO2-PaCO2/0.8; normally, PIO2=150; A-a gradient=PAO2-PaO2=10-15 (high in hypoxemia from VQ mismatch, responsive, inoperable; NET (Kulchitsky cells=dark)
shunting, fibrosis); R=respiratory quotient=CO2 produced/O2 consumed bronchial adenoca periph prior pulmonary injury site; nonsmokers Clara cell,
hypoxemia=low PaO2, hypoxia=low O2 delivery to tissue (anemia, low cardiac output), ischemia=loss of flow bronchioalveolar periph grows along airways (pneumonia-like), multiple
ventilation and perfusion are greater at the lung base, but V/Q=0.6; shunt: 100% O2 doesn't improve PO2 can cause hypertrophic osteoarthropathy densities
CO2 back to lungs: bound to Hb at N terminus as carbaminoHb (5%), dissolved (5%), bicarb (90%, H produced bound to heme; O2 Large CC periph highly anaplastic, surgical tx, poor prognosis; giant cells w/
binding at lung promotes dissociation of H-Hb and CO2 formation [Haldane effect]) leukocyte fragments in cytoplasm
DVT: Homans' sign=tender calf on dorsiflexion of foot; Virchow's triad: stasis, hypercoag, endothelial damage pneumonic "coin" lesion on XR, noncalcified nodule on CT; mets to brain (epilepsy), liver (jaundice,
COPD chronic bronchitis: mucus-gland hypertrophy (high Reid index), small airway dz, wheezing, crackles, shunting causes early- HM), adrenal, bone (break); met from breast, colon, prostate, bladder
onset hypoxemia, late-onset dyspnea; emphysema: destruction of alveolar walls, large air spaces, low elasticity, pursed-lip breathing, complications: SVC Sz, Pancoast (Horner's), paraneoplastic, effusions, hoarseness
decreased breath sounds, tachycardia, early onset dyspnea, late onset hypoxemia (loss of capillary beds); asthma: bronchial
hyperresponsiveness, Cushmann's spirals (shed epithelium on mucous plugs), low I/E ratio, pulsus paradoxus; bronchiectasis: chronic
ARDS: diffuse alveolar damage, protein-rich leakage into alveoli, forms haline membrane, initial
infxn of bronchi causes permanent airway dilation, hemoptysis, aspergillosis, from CF, Kartagener's
damage from PMNs, coagulation cascade, or free radicals; from intravascular (sepsis, shock, uremia,
amniotic fluid embolism) or extravascular (trauma, gastric aspiration, acute panc) cause; NRDS:
persistently low O2 increases risk of PDA; therapeutic O2 causes retinopathy of prematurity
emphysema centriacinar=smoking; panacinar=α1AT; paraseptal=bullae, rupture=spontaneous pneumothorax
asbestosis: ivory white calified pleural plaques, asbestos bodies in macrophages, bronchogenic ca, LLs
upper lobes: coal miner's (cor pulmonale), silicosis (macrophages release fibrogenic factors, hilar LN eggshell calcifications; silica disrupts phagolysosome, impairs macrophages, increased susceptibility to TB)
Name Sx Pathophys Other
Addison's Dz hypotn, hyperkalemia, acidosis, skin hyperpigmentation chronic primary adrenal insufficiency (atrophy or destruction)
Albright's hereditary hypocalcemia, tetany, shortened 4th/5th digits, short stature AD bilateral renal unresponsiveness to PTH aka pseudohypoPTH
osteodystrophy
Alport's Sz progressive heridetary nephritis, deafness, and cataracts abnormal type IV collagen usually XLR
Alzheimer's Dz dementia, can get intracranial hemorrhage, cortical atrophy, intracellular APP degradation by β-/γ-secretase yields N-APP (DR6L) or Aβ40/42 (cell death signal or early=APP, presenilin-1/-2; late=ApoE4;
neurofibrillary tangles (hyperphosphorylated tau) aggregate into plaques), decreased ACh ApoE2=protective (degrades plaques)
Andersen's Dz cirrhosis and death w/i 5y branching enzyme def, glycogen pptation ABCD: Andersen's=branching
Angelman's Sz retardation, seizures, ataxia, inappropriate laughter deletion of maternal chromosome 15
Becker's MD mm weakness, presents in early adulthood XLR mutated dystrophin gene less severe than DMD
Berger's Dz nephritic sz (PHAROH), mesangial immune deposits presents/flares w/ URI or acute gastroenteritis, assn w Henoch Schonlein aka IgA glomerulonephropathy, adults
Boerhaave Sz transmural esophageal rupture violent retching (alcoholics, bulemics)
Broca's aphasia nonfluent, intact comprehension inferior frontal gyrus
Budd-Chiari Sz congestive liver disease: HSM, ascites, abd pain, liver failure, varices, NO JVD occlusion of IVC or hepatic veins causes centrilobular congestion and necrosis; assn w
polycythemia, HCC, pregnancy, hypercoaguable state
Buerger's Sz intermittent claudication, severe pain, superficial nodular phlebitis, Raynaud's, medium-sized vessels, idiopathic segmental thrombosing vasculitis; seen in heavy
can cause gangrene and autoamputation smokers
Caplan's Sz cough, SOB, joint inflammation (RA) pneumoconiosis + rheumatoid arthritis
Chagas' Dz dilated CM, megacolon, megaesophagus Trypanosoma cruzi (protist), from reduviid bug tx=nifurtimox
Charcot-Bouchard Sz microaneurysms in small vessels (basal ganglia, thalamus) associated w chronic htn
Charcot-Marie-Tooth Sz aka hereditary motor and sensory neuropathy (HMSN) defective protein production, presents in childhood
Chediak-Higashi Sz recurrent pyogenic infxn, partial albinism, peripheral neuropathy, large microtubule polymerization defect causes decreased phagocytosis
lysosomal vescicles in phagocytes
Cheyne Stokes breaths oscillating slow/fast breathing central apnea in CHF or high ICP
Chiari malformation II: assn w/ aqueductal stenosis, hydrocephaly, syringomyelia, lumbar cerebellar tonsil herniation; I: asxatic; II: large vermian displacement
meningomyelocele
Churg-Strauss Sz usually asthma, sinusitis, skin lesions, peripheral neurophathy (wrist/foot drop); p-ANCA, granulomatous vasculitis w/ eosinophilia
can also hit heart, GI, kidneys
Conn's Sz htn, hypokalemia, MAlk aldosterone secreting tumor, can be bilateral
Cori's Dz mild form of von Gierke's (gluconeogenesis intact), no LAc debranching enzyme (α-1,6-glucosidase) def ABCD: Cori's=debranching
Creutzfeldt-Jakob Dz rapidly progressive dementia with myoclonus prions cause α-helix to β-sheet transformation spongiform cortex
Cri-du-chat Sz microcephaly, retardation, epicantal folds, cardiac problems congenital microdeletion of 5p
Crigler-Najjar Sz, type 1 early death, jaundice, kernicterus, high indirect bilirubin absent UDPGT causes large increase in unconjugated bilirubin tx=plasmapheresis, phototherapy
Crigler-Najjar Sz, type 2 high indirect bilirubin, can be treated with phenobarbital low UDPGT causes large increase in unconjugated bilirubin
Curling's ulcer acute gastritis and ulcer burns cause low plasma volume, causing sloughing of the gastric mucosa
Cushing's ulcer acute gastritis and ulcer brain injury causes increased vagal stimulation, increasing H+ production
Dandy-Walker Sz assn w/ hydrocephalus, spina bifida, posterior fossa enlargement absence of cerebellar vermis, large fourth ventricle
DiGeorge Sz parathyroid/thymic aplasia (hypoCa/TC def), cardiac defects (TOF, truncus 22q11 microdeletion causes aberrant development of 3rd and 4th branchial pouches
arteriosus)
Dressler's Sz low grade fever, pleuritic chest pain, pericarditis (self-limited) autoimmune fibrinous pericarditis, several weeks post-MI
Dubin-Johnson Sz conjugated hyperbilirubinemia, grossly black liver, benign liver glucuronyl transferase deficiency (excretion of conjugated bilirubin)
Duchenne's MD mm weakness, begins in pelvig girdle, progresses superiorly, pseudohypertrophy XLR frameshift mutation, deletion of dystrophin gene, fibrofatty displacement of mm
of calf/delt, DCM, Gowers' maneuver (use of arms to stand), presents <5yo, high
CPK
Edwards' Sz microcephaly, rocker-bottom feet, clenched hands, heart defect trisomy 18 (after 21, most common trisomy resulting in live birth)
Ehlers-Danlos Sz hyperextensible skin, bleeding tendency/aneurysms/organ rupture, hypermobile faulty collagen synthesis (usually type III, sometimes I, 6 types) 6 types, severity and inheritance vary
joints/dislocations
Eisenmenger's Sz PAH, late cyanosis, clubbing, polycythemia uncorrected VSD, ASD, or PDA causes RVH and shunt reversal
Endemic Typhus rash starts centrally and spreads outward, fever, headache Rickettsia typhi (fleas)
Epidemic Typhus rash starts centrally and spreads outward, fever, headache Rickettsia prowazekii (lice)
Fabry's Dz peripheral neuropathy (esp hands and feet), angiokeratomas, cardiovascular and α-galactosidase A def causes ceramide trihexose accumulation XLR
renal diseases
Fanconi's anemia aplastic anemia, short stature, tumors/AML (high risk) AR, DNA repair gene mutations (ubiquitinization of damaged DNA)
Fanconi's Sz polyuria, acidosis, growth failure, electrolyte imbalances proximal tubule resorption defect
Name Sx Pathophys Other
Fitz-Hugh-Curtis Sz acute RUQ pain, referred to R shoulder, "violin string" appearance inflammation from PID (esp N. gonorrhea) spreads to liver capsule

Friedrich's ataxia staggering gait, frequent falls, nystagmus, dysarthria, pes cavus, hammer toes, AR (GAA) repeat in frataxin causes mitochondrial impairment
HCM (cause of death), presents as childhood kyphoscoliosis

Gardner's Sz CRC, osteomas, and soft tissue tumors, retinal hyperplasia FAP + osseous and soft tissue tumors, retinal hyperplasia
Gaucher's Dz HSM, osteoporosis, aseptic necrosis of femur/bone crises, mental retard., β-glucocerebrosidase def causes glucocerebrosidase accumulation
Gaucher's cells (macrophages look like crumpled paper)
Gerstmann Sz acalculia, agraphia, finger agnosia, L/R disorientation dominant parietal lobe lesion
Gilbert Sz benign mild jaundice with stress/fasting mildly low UDPGT or bili uptake, in stress, elevated unconjugated bilirubin
Glanzmann's thrombasthenia increased bleeding time, normal platelet count, smear shows no clumping GpIIb/IIIa def, no platelet plug formation

Guillan-Barre Sz symmetric,rapidly-ascending mm weakness, begins in distal LE, facial paralysis in inflammation and demyelination of peripheral nn (motor>sensory), infiltrate in high CSF protein w/ nl cell count=
50%, papilledema, autonomic dysfunction not uncommon (htn, eg); usually endoneurium, C. jejuni and HSV are common antecedents, type IV hypersensitivity, high albuminocytologic dissociation; tx=IVIG, respiratory
resolves wks-mos CSF protein, nl cell count support, plasmapheresis
Hartnup Dz pellagra (diarrhea, dermatitis, dementia) from low tryptophan defective neutral AA transporter on intestinal and renal epithelium AR
Henoch-Schonlein purpura skin rash (palpable purpura) on buttocks and legs, arthralgias, intestinal small vessel vasculitis, IgA immune complexes, assn w/ IgA nephropathy; commonly mnemonic: Jenock-S P=Joints, Skin, Panc;
hemorrhage, abdominal pain, melena follows URI commonest childhood systemic vasculitis
Hirschsprung Dz congenital megacolon, constipation, failure to pass meconium failure of migration of neural crest cells; no plexuses in intestines assn w/ Down's Sz
Hunter's Sz mild Hurler's, no corneal clouding, aggressive behavior iduronate sulfatase def causes heparin sulfate and dermatan sulfate accumulation XLR
Huntington's Dz chorea, athetosis (writhing fingers), dementia, aggression, depression (mistaken NMDA excitotoxicity causes atrophy of striatal nuclei (loss of ACh and GABA) cause loss
for substance abuse sometimes) of motion inhibitors chromosome 4, AD (CAG)n expansion, anticipation
Hurler's Sz developmental delay, gargoylism, airway obstruction, corneal clouding, HSM α-L-iduronidase def causes heparin sulfate and dermatan sulfate accumulation

I-cell (inclusion) dz coarse facial features, clouded corneas, restricted joint movement, high plasma failure of addition of M6P to lysosome proteins, so they are excreted instead often fatal in childhood, similar to Hurlers
levels of lysosomal proteins
Jarisch-Herxheimer rxn fever, chills, headache, myalgia after syphilis tx lysis of spirochetes causes toxin release
Jervell and Lange-Nielsen Sz long QT, sensorineural hearing loss K channel mutation AR, rare
Job's Sz coarse facies, "cold" abscesses, retained primary teeth, hyper-IgE, derm IFN-γ deficiency, neutrophils don't respond to chemotactic stimuli
problems (eczema), recurrent colds
Kallmann Sz lack of 2° sex characteristics (hypogonadotropic), anosmia no migration/development of neural cells
Kartagener's Sz infertility, bronchiectasis, recurrent sinusitis, situs inversus dynein arm defect causes immotile cilia
Kawasaki's Dz fever, conjunctivitis, strawberry tongue, lymphadenitis, desquam-ative skin rash, medium-sized vessels, self-limited necrotizing vasculitis in infants/kids, esp asians tx=IVIG, aspirin
can develop coronary aneurisms (esp if untxed)
Kluver-Bucy Sz hyperorality, hypersexuality, disinhibited behavior bilateral amygdala lesion
Krabbe's Dz galactocerebrosidase def causes galactocerebroside accumulation peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Krukenberg's tumor abundant mucous, signet ring cells gastric adenocarcinoma mets bilaterally to ovaries
Lambert-Eaton Sz difficulty climbing stairs, rising from chair, eye sx come later (as opposed to MG Abs against presynaptic Ca channels at NMJ, can be paraneoplastic
where they are early), no reversal w/ AChEIs
Lesch-Nyhan Sz retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis defective HGPRT (purine salvage pathway) causing buildup of uric acid XLR

Leser-Trelat Sign sudden appearance of multiple seborrheic keratoses underlying malignancy (mostly GI adenocarcinomas)
Lewy Body dementia Parkinsonism w/ dementia and hallucinations α-synuclein defect
Libman Sachs sterile endocarditis, usually benign wart-like vegetations, from SLE
Li-Fraumeni Sz sarcomas at a young age, many cancers while young AD, mutations in p53 cause increased susceptibility to cancers
Loffler's Sz eosinophilic infiltrate and endocardial fibrosis or parasitic pneumonia
Lynch Sz 80% progress to CRC, proximal colon always involved AD mutation of DNA mismatch repair gene aka HNPCC
Mallory-Weiss Sz hematemesis vomiting (alcoholics, bulemics) causes mucosal laceration at GE junction
Marfan's Sz tall, long extremities, pectus excavatum, hyperextensive joints, arachnodactyly, fibrillin defect (scaffold for tropoelastin, makes elastin), lack of elasticity
aortic regurg/dissecting aortic aneurysms (cystic medial necrosis of aorta), MVP,
superotemporal lens subluxation
McArdle's Dz cramps, myoglobinuria w/ exercise muscle glycogen phosphorylase def McArdle's for Muscle
Name Sx Pathophys Other
McCune-Albright Sz multiple unilateral bone lesions and café-au-lait spots, endocrine abnormalities type of polyostotic fibrous dysplasia (bone replaced by fibroblasts, collagen, irregular mnemonic: POOCH= pit tumors, ovarian cysts,
(PRL/GHoma, precocious puberty, hyperthyroid) ovarian cysts trabeculae, many bones affected) osteomalacia, café-au-lait spots, hyperthyroid

Meigs' Sz ovarian fibroma, ascites, pleural effusion (usually R sided transudate), pulling sensation in groin
Menetrier's Dz cerebriform rugae, edema, wt loss, precancerous increased gastric mucosal secretion, protein loss, parietal cell atrophy
Meniere's Dz vertigo (relapsing/remitting), hearing loss, tinnitus hydrops in labrynth
Myasthenia Gravis dyplopia, ptosis, reversal w/ AChEI Abs against postsynaptic AChR, worsen w/ muscle use, assn w/ thymoma most common NMJ disorder
Neimann-Pick Dz progressive neurodegeneration, developmental delay, cherry red macula, foam sphingomyelinase def causes sphingomyelin accumulation
cells, HSM
Osler-Weber-Rendu Sz telangiectasias, recurrent epistaxis, skin discolorations, AVMs AD inherited disorder of blood vessels
Paget's Dz increased hat size, CN impingement, chalk-stick fractures, high output cardiac high osteoblast and osteoclast activity, abnormal bone architecture; high alk phos, aka osteitis deformans
failure (increased AV shunts), mosaic patterning normal Ca and PO4
Parinaud Sz paralysis of conjugate vertical gaze lesion in superior colliculi (pinealoma)
Parkinson's Dz pill-rolling tremor (at rest), cogwheel rigidity, brady-/a-kinesia, postural loss of DAergic neurons in substantia nigra pars compacta cause unchecked inhibitory rx-induced: metoclopramide, reserpine,
instability, Lewy bodies (intracellular α-synuclein) input on thalamus (ACh) haloperidol/chlorpromazine
Patau's Sz microcephaly, rocker-bottom feet, cleft lip/palate, holoprosencephaly, trisomy 13
polydactyly, congenital heart dz
Peutz-Jeghers Sz GI hamartomas (polyps), hyperpigmentation of mouth/feet/hands AD, increased risk of CRC/other visceral malignancies polyps can cause obstruction
Pick's Dz dementia, aphasia, Parkinsonian, change in personality, Pick bodies frontotemporal atrophy (spares parietal lobe and posterior 2/3 of central gyrus) aka frontotemporal dementia
(hyperphosphorylated intracellular tau)
Plummer-Vinson Sz anemia, atrophic glossitis, dysphagia (esophageal webs) iron deficiency
Pompe's Dz cardiomegaly/restrictive CM, exercise intolerance, neuro sx lysosomal α-1,4-glucosidase def Pompe's hits the pump
Potter's Sz limb/facial deformities, pulmonary hypoplasia, oligohydramnios bilateral renal agenesis (usually ureteric bud malformation) or posterior urethral valves
(M, imperforate urethra)
Pott's Dz vertebral narrowing/collapse, spinal mass, back pain TB infxn of 2 adjacent vertebral bodies causes avascularity of disc
Prader-Willi Sz retardation, hyperphagia, obesity, hypogonadism, hypotonia deletion of paternal chromosome 15
Reiter's Sz conjunctivitis/anterior uveitis, urethritis, arthritis (large joint) post-GI or chlamydia infxn aka reactive arthritis
Reye's Sz mitochondrial abnormalities, microvescicular fatty liver, hypoglycemia, coma, viral infxn (esp VZV/flu) txed w/ salicylates, aspirin metabolytes decrease β-ox by rare, often fatal
hepatoencephalopathy reversible inhibition of mitochondrial enzyme
Riedel's thyroiditis rock-hard, non-tender goiter, hypothyroidism thyroid replaced by fibrous tissue
Rotor's Sz very mild conjugated hyperbilirubinemia low liver glucuronyl transferase (excretion of conjugated bilirubin)
Samter's triad asthma attack, hypersensitivity, nasal polyps trigger=aspirin to an asthmatic
Sezary Sz cutaneous patches and nodules, indolent CD4+ TC lymphoma aka mycosis fungoides
Sheehan Sz (postpartum) no lactation, absent menstruation, cold intolerance pituitary infarct
Shwartzman rxn vasculitis from exposure to endotoxin causing glomerular thrombi more common during birth (N. meningitides)
Sturge-Weber Dz facial port-wine stain (nevus flammeus), pheo, ipsilateral lepto-meningioma congenital vasculitis, small vessels, sporadic
(intracerebral AVM), seizures, early-onset glaucoma
Takayasu's arteritis fever, night sweats, high ESR, myalgias, arthritis, ocular disturbances, weak granulomatous thickening of proximal great vessels, seen mostly in Asian F<40 aka pulseless dz
pulses in upper extremities
Tay-Sach's Dz progressive neurodegeneration, developmental delay, cherry red macula, hexosaminidase A def causes GM2 ganglioside accumulation
lysosomes w/ onion skin, no HSM
Temporal arteritis unilateral headache, jaw claudication, impaired vision (occlusion of ophthalmic focal granulomatous inflammation of large vessels, seen mostly in elderly F; half of pts aka giant cell arteritis
artery), high ESR have polymyalgia rheumatica
Treacher-Collins Sz mandibular hypoplasia, facial abnormalities, hearing loss failure of migration of neural crest cells of 1st branchial arch
Trousseau's Sz migratory thrombophlebitis paraneoplastic (esp GI adenocarcinoma)
Turcot's Sz colon and malignant CNS tumors FAP + malignant CNS tumors
Typhoid fever fever, diarrhea, headache, rose spots on abdomen Salmonella typhi, can remain in GB chronically
von Gierke's Dz severe fasting hypoglycemia, increased glycogen in liver, hepatomegaly, lactic glucose-6-Pase deficiency GSD mnemonics: 1-5=VP CAM; PoLys:
acidosis, gout Pompe's=lysosomal
von Hippel-Lindau Dz hemangioblastomas of retina/cerebellum/medulla, bilateral RCC, pheo, etc deletion of VHL (tumor suppressor) on ch. 3 cuses constitutive expression of HIF
(hypoxia-inducible factor) causing angiogenesis
Waldenstrom's M spike on electrophoresis, hyperIgM, hyperviscosity sx, no lytic bone lesions
macroglobulinemia (like in multiple myeloma)
Name Sx Pathophys Other
Wallenberg's Sz contralateral pain/T loss, ipsilateral dysphagia, hoarseness, no gag reflex, lateral medullary syndrome (PICA); lateral spinothalamic, nuc ambiguus, VIII,
vertigo/diplopia, ipsilateral Horner's, ipsilateral face sensation loss, ipsilateral sympathetics, spinal tract and nuc of V, inferior cerebellar peduncle
ataxia
Waterhouse-Friderichsen Sz organ failure, coma, death, hypotn, shock, DIC, no meningitis acute primary adrenal insufficiency from adrenal hemorrhage; from N. meningitides
sepsis, DIC, endotoxic shock
Wegener's granulomatosis cough, dyspnea, hemoptysis, hematuria/red cell casts, chronic sinusitis, otitis c-ANCA positive, focal necrotizing vasculitis (small vessels), necrotizing granulomas of the tx: cyclophosphamide, corticosteroid
media, mastoiditis lung/upper airway, and necrotizing GN
Weil's Dz jaundice, azotemia, hemorrhage, anemia, fever, photophobia icterohemorrhagic leptospirosis (spirochete); surfers in the tropics
Wenckebach usually asxatic progressive lengthening of PR until beat is dropped aka Mobitz type I 2nd degree heart block
Werdnig-Hoffman Sz floppy baby at birth, tongue fasciculations, death by 7mo AR degeneration of anterior horns (LMN only) aka infantile spinal muscular atrophy
Wernicke-Korsakoff Sz confusion, ophthalmoplegia, ataxia bilateral mammillary body lesion (B1 def) stranger would notice
Wernicke-Korsakoff Sz anterograde amnesia, confabulation, personality changes bilateral mammillary body lesion (B1 def) friends would notice
Wernicke's aphasia fluent, impaired comprehension superior temporal gyrus
Whipple's Dz arthralgias, cardiac and neuro involvement Tropheryme whippelii (GP, PAS positive, in macrophages) older men usually
William's Sz elfin facies, retardation, hyperCa, overly friendly, CV problems congenital microdeletion of 7q (includes elastin)
Wilson's Dz Kayser-Fleischer rings, hemolytic anemia, cirrhosis, asterixis, HCC, basal ganglia inadequate Cu excretion, low ceruloplasmin (conjugated, plasma-safe version of Cu); aka hepatolenticular degeneration;
degeneration, dementia, dyskinesia, dysarthria accumulation everywhere tx=penicillamine
Wiskott-Aldrich Sz thrombocytopenic purpura, infxns, eczema; high IgE/A, low IgM XLR, progressive deletion of BC and TC
Wolff-Parkinson-White ventricles partially depolarize earlier, delta-wave on ECG accessory conduction band (bundle of Kent) bypasses AV node can lead to reentry SVT
 Neuro
Name Sx Pathophys Other
Huntington agression, depression, dementia, chorea, athetosis NMDA excitotoxicity causes atrophy of striatal nuclei (loss of ACh and chromosome 4, AD (CAG)n expansion, anticipation; drug-induced:
(writhing fingers) GABA) cause loss of motion inhibitors haloperidol/chlorpromazine, reserpine, metoclopramide
Parkinson pill-rolling tremor (at rest), cogwheel rigidity, brady-/a- loss of DAergic neurons in substantia nigra pars compacta cause Lewy bodies (α-synuclein intracellular inclusions)
kinesia, postural instability increased inhibitory input on thalamus
Alzheimer dementia, can get intracranial hemorrhage APP degradation by β-/γ-secretase yields N-APP (DR6L) or Aβ40/42 cortical atrophy, decreased ACh, intracellular neurofibrillary tangles
(cell death signal or aggregate into plaques) (hyperphosphorylated tau); early onset=APP, presenilin-1/-2; late=ApoE4;
ApoE2=protective (degrades plaques)
Pick's Dz (FTD) dementia, aphasia, Parkinsonian, change in personality frontotemporal atrophy (spares parietal lobe and posterior 2/3 of aka frontotemporal dementia; Pick bodies (hyperphosphorylated intracellular tau)
central gyrus)
Lewy Body dementia Parkinsonism w/ dementia and hallucinations α-synuclein defect
Creutzfeldt-Jakob Dz rapidly progressive dementia with myoclonus prions cause α-helix to β-sheet transformation spongiform cortex
normal pressure hydrocephalus urinary incontinence, ataxia, dementia expanding ventricles cause corona radiata distortion (no increase in
subarachnoid space volume)
MS internuclear ophthalmoplegia (nystagmus, dyplopia), autoimmune inflammation and demyelination of CNS; commonly hits CSF: increased protein (IgG, oligoclonal bands are dxtic); periventricular plaques
scanning speech, intention tremor, incontinence, optic MLF, optic nerve, spinal cord (oligodendrocyte loss, reactive gliosis), preservation of axons; tx: β-IFN,
neuritis (loss of vision), hemisensory sx; immunosuppression, sxatic tx for neurogenic bladder, spasticity, pain
relapsing/remitting
ammonia intoxication tremor, slurring speech, somnolence, vomiting, cerebral NH4 depletes α-KG, inhibiting TCA cycle; OTC is most common urea tx: benzoate, lactulose, or phenylbutyrate (bind AAs and lead to excretion in
edema, blurred vision cycle disorder urine)
pellagra diarrhea, dementia, dermatitis (glossitis) B3 def (can be from Hartnup's, carcinoid sz, low B6)
Renal
Immune deposits
Sub-epithelial Sub-endothelial Mesangial
Membranous GN Cryoglobulinemia Berger's Dz (IgA nephropathy)
Postinfectious GN Membranoproliferative GN
Lupus nephritis V Lupus nephritis III-V Lupus nephritis II-V

Immunofluorescence Pattern
Granular Linear Light and Dark Areas
Membranous nephropathy Goodpasture's Berger's Dz (IgA nephropathy)
Postinfectious GN
Membranoproliferative GN

Other Characteristics
Diffuse Glomerular Proliferation Low Complement
Postinfections GN Postinfectious GN
Membranoproliferative GN Membranoproliferative GN
SLE Cryoglobulinemia
SLE
Microbio
Name Pathophys Sx Other
von Gierke's Dz (type I) glucose-6-Pase deficiency severe fasting hypoglycemia, increased glycogen in liver, GSD mnemonics: 1-5=VP CAM
hepatomegaly, lactic acidosis, gout,
Pompe's Dz (II) lysosomal α-1,4-glucosidase def cardiomegaly, muscular, neuro sx Pompe's hits the pump; PoLys: Pompe's=lysosomal
Cori's Dz (III) debranching enzyme (α-1,6-glucosidase) def mild form of von Gierke's (gluconeogenesis intact) ABCD: Andersen's=branching, Cori's=debranching
Andersen's Dz (IV) branching enzyme def, glycogen pptation cirrhosis and death w/i 5y
McArdle's Dz (V) muscle glycogen phosphorylase def cramps, myoglobinuria w/ exercise McArdle's for Muscle
Gaucher's Dz β-glucocerebrosidase def causes glucocerebrosidase HSM, aseptic necrosis of femur/bone crises, Gaucher's cells most common
accumulation (macrophages look like crumpled paper)
Krabbe's Dz galactocerebrosidase def causes galactocerebroside peripheral neuropathy, developmental delay, optic atrophy, globoid
accumulation cells
Fabry's Dz α-galactosidase A def causes ceramide trihexose peripheral neuropathy (esp hands and feet), angiokeratomas, XLR
accumulation cardiovascular and renal diseases
Tay-Sach's Dz hexosaminidase A def causes GM2 ganglioside progressive neurodegeneration, developmental delay, cherry red
accumulation macula, lysosomes w/ onion skin, no HSM
Neimann-Pick Dz sphingomyelinase def causes sphingomyelin accumulation progressive neurodegeneration, developmental delay, cherry red
macula, foam cells, HSM
Hurler's Sz α-L-iduronidase def causes heparin sulfate and dermatan developmental delay, gargoylism, airway obstruction, corneal
sulfate accumulation clouding, HSM
Hunter's Sz iduronate sulfatase def causes heparin sulfate and mild Hurler's, no corneal clouding, aggressive behavior XLR
dermatan sulfate accumulation
I-cell (inclusion) dz failure of addition of M6P to lysosome proteins, so they Hurler's, + restricted joint movement, high plasma levels of lysosomal
are excreted instead proteins, gingival hyperplasia
metachromic leukodystrophy arylsulfatase A deficiency causes cerebroside sulfate cerntral and peripheral demyelination with ataxia, dementia
accumulation
Vasculitides
Name Pathophys Sx
Wegener's granulomatosis focal necrotizing: vasculitis, granulomas of upper cough, dyspnea, hemoptysis, chronic sinusitis, otitis media,
airways/lung, and GN; c-ANCA hematuria/RBC casts, mastoiditis
microscopic polyangiitis same as Wegener's, lacks granulomas; p-ANCA
primary pauci-immune vasculitis only of kidneys
crescentic GN
Churg-Strauss granulomatous small-vessel vasculitis w/ eosinophilia; p- usually asthma, sinusitis, skin lesions, peripheral nephropathy; can
ANCA also involve heart, GI, kidneys
Sturge-Weber congenital vascular disorder, small vessels facial port-wine stain (nevus flammeus), ipsilateral leptomeningeal
angiomatosis, seizures, early glaucoma
Henoch-Schonlein purpura IgA immune complexes, assn w/ IgA nephropathy palpable purpura on thighs/butt, arthralgias, intestinal hemorrhage, most common childhood systemic vasculitis
abdominal pain, melena
Buerger's dz idiopathic segmental thrombosing vasculitis of medium intermittent claudication, superficial nodular phlebitis, Raynaud's, aka thromboangiitis obliteralns
vessels, seen in heavy smokers severe pain, can cause gangrene
Kawasaki's Dz acute, self-limited necrotizing middle-sized vasculitis, in fever, conjunctivitis, strawberry tongue, lymphadenitis, desquamative tx=IVIG, aspirin
infants/kids, esp asians skin lesions, can cause coronary aneurisms
Takayasu's arteritis granulomatous thickening of proximal great vessels; Asian fever, night sweats, myalgia, arthtiris, skin nodules, weak pulses in UE, aka pulseless disease
F<40, high ESR ocular disturbances
temporal arteritis focal granulomatous inflammation of large a jaw claudication, unilateral headache, vision disturbance high ESR, mostly in elderly F, half of pts have polymyalgia rheumatica
 Cardio
disease tx other
essential htn diuretics, ACEI, ARBs, CCB
htn in CHF diuretics, ACEI, ARBs, CCB, β blockers no β blockers in decompensated CHF, esp K-sparing diuretics
htn in DM ACEI, ARBs, CCB, diuretics, β-blocker, α-blocker ACEI protective against diabetic nephropathy
malignant htn nitroprusside, fenoldopam, diazoxide
angina nitrates and β-blockers
AFib digoxin, β-blockers, anticoag, non-DHP
AFlutter ablation, anticoag, non-DHP
SVT class IA/C, class II, class IV, adenosine
VT class I, class II

Neuro
disease tx
tonic clonic seizure first line: phenytoin, carbamazepine, valproate first line in pregnancy and children: phenobarbital
absence seizure first line: ethosuximide; otherwise, valproate
status seizure acute: BDZ; prophylaxis: phenytoin
 -statin
-TAXOLs
(bival)-IRUDIN
(cis/carbo)-PLATIN
(etid)-RONATE
(eto)-POSIDE (VP-16)
(par/flu)-oxetine
(praz)-osin
(zafir)-lukast
2,4-DNP
5-FU
6-MP
6-thioguanine (6TG)
abciximab
acarbose
acebutolol
acetaminophen
acetazolamide
acute EtOH
acyclovir
adalimumab
adenosine
Al(OH)3
albendazole
albuterol
aldesleukin
allopurinol
alprazolam
Amanita phalloides (poison
mushroom)
amantidine
amantidine
amifostine
amikacin
amiloride
amiodarone
amitriptyline
amoxicillin
amphetamine
amphotericin B
ampicillin
anastrozole
anistreplase
antimycin A
aripiprazole
arsenic
ascorbic acid
aspart
aspirin (ASA)
atenolol
atomoxitene
atropine
azathioprine
azithromycin
aztreonam
beclomethasone
benzene
benztropine
betaxolol
bethanechol
biotin
bismuth
bleomycin
bosentan
bretylium
brimonidine
bromocriptine
bromocriptine
buprenorphine
bupropion
buspirone
busulfan
butorphanol
cabergoline
CaCO3
caffeine
calcitriol (D3)
captopril
carbachol
carbamazepine
carbenicillin
carvedilol
caspofungin
cefalcor
cefazolin
cefipime
cefoxitin
ceftazidime
ceftriaxone
cefuroxime
celecoxib
cephalexin
certirizine
chloramphenicol
chlordiazepoxide
chloroquine
chlorpheniramine
chlorpromazine
chlorpropamide
cholestyramine
chronic EtOH
cimeTIDINE
ciprofloxacin
citalopram
clarithromycin
class I antiarrhythmics

clavulanic acid
clinda-/linco-mycin
clofazimine
clomiphene
clomipramine
clonidine
clopidogrel
clozapine
CO
cobalamin
cocaine
codeine
colchicine
colesevelam
colistimethane
copper (Wilson's)
cromolyn
cyanide
cyclophosphamide
cyclosporine
cytarabine (ara-C)
DA
daclizumab
dactinomycin
dalfopristin
dantrolene
dapsone
daunorubicin
delaviridine
demeclocycline
Depressants
desipramine
desloratadine
desmopressin (ddAVP)
detemir
dexamethasone
dexedrine
dextromethorphan
diazepam
diazoxide
dicloxacillin
didanosine (ddI)
diethylcarbamazine
diethylstilbestrol
digoxin
digoxin immune Fab
diltiazem (non-DHP)
dinoprostone
diphenhydramine
diphenoxylate
disopyramide
dobutamine
dofetilide
donepezil
doxorubicin (adriamycin)

doxycycline
Drug
Drug
Drug
Drug
Drug
Drug
Drug
Drug
Drug
Drug
Drug
Drug
drug
Drug/Type
duloxetine
dynorphin
echothiophate
edrophonium
efavirenz
enalapril
enflurane
enfuvirtide
enkephalin
enoxacin
enoxaparin
ente-/tol-capone
ephedrine
epinephrine
eplerenone
ergonovine
erythromycin
erythropoietin
esmolol
eszopiclone
etanercept
ethacrynic acid
ethambutol
ethinyl estradiol
ethosuximide
ethylene glycol
exemestane
exenatide
ezetimibe
famciclovir
famoTIDINE
fenoldopam
fentanyl
fexofenadine
filgrastim
finasteride
flecainide
fluconazole
flucytosine
fluphenazine
flutamide
folate
foscarnet
fosfentoin
furosemide
gabapentin
galantamine
gangciclovir
gemfibrozil
gentamicin
GH
glargine
glimepiride
glipizide
glyburide
glycopyrrolate
gold
griseofulvin
guaifenesin
guanethidine
Hallucinogens
haloperidol
halothane
heme and glucose
heparin
heroin
hexamethonium
HRT
hydralazine
hydrochlorothiazide
hydrocortisone
hydroxyurea
ibuprofen
ibutilide
IFN-α
IFN-β
IFN-γ
ifosfamide
imatinib (Gleevec)
imipenem/cilastatin
imipramine
indiNAVIR
indomethacin
infliximab
INH (isoniazid)
insulin
ipratropium
iron (hemochromatosis)
isocarboxazid
isoproterenol
isosorbide dinitrate
ivermectin
K
ketamine
ketoconazole
ketorolac
labetalol
lamotrigine
lansoprazole
latanoprost
lead
leuprolide
levetiracetam
levodopa/carbidopa
levothyroxine
lidocaine
linezolid
lisinopril
lispro
lithium
loperamide
loratadine
lorazepam
LSD
mannitol
maprotiline
marijuana
mebendazole
mefloquine
melacortin
memantine
meperidine
mercury
meropenem
mestranol
metaproterenol
metformin
methacholine
methadone
methanol
methemoglobin
methicillin
methimazole
methotrexate (MTX)
methoxyflurane
methscopolamine
methylphenidate
methyltestosterone
metoclopramide
metoprolol
metronidazole
metyrosine
mexiletine
Mg
Mg(OH)2
MgSO4
miconazole
mifepristone (RU-486)
miglitol
minocycline
mirtazapine
misoprostol
moricizine/encainide
morphine
muromonab-CD3 (OKT-3)

Na stibogluconate
N-acetylcysteine
nadolol
nafcillin
Name
naproxen
NE
neomycin
neostigmine
nevirapine
niacin
niacin (also see vitamin
section)
nicotine
nife-/amlo-dipine (DHP)

nifurtimox
nitrofurantoin
nitroglycerin
nitroprusside
nitrosurea (-
mustines)
nizaTIDINE
notriptyline
NPH
nystatin
octreotide
olanzapine
oligomycin
omeprazole
ondansetron
oprelvekin
organophosphates
oseltamivir
ouabain
oxazepam
oxybutynin
oxytocin
paclitaxel
palivizumab
pancuronium
pantothenate
PCP
penicillin
pentamidine (aerosolized)
phencyclidine
phenelzine
phenobarbital
phenoxybenzamine
phentolamine
phenylephrine
phenytoin
physostigmine
pilocarpine
pindolol
pioglitazone
piperacillin
pirenzepine
pralidoxime
pramipexole
pramlintide
praziquantel
prednisone
probenecid
procainamide
procarbazine
progestin
propafenone
propantheline
propofol
propranolol
propylthiouracil
pyrantel pamoate
pyrazinamide
pyridostigmine
pyridoxal P
pyrimethamine
quetiapine
quinidine
quinine
quinupristin
raloxifene
raniTIDINE
reisperidone
reserpine
retinol
ribavirin
riboflavin
rifampin
riluzole
rimantidine
ritodrine
rituximab
rivastigmine
ropinirole
rosiglitazone
rotenone
salicylate
salmeterol
saquiNAVIR
sargramostim
scopolamine
selegiline
sertraline
sildenafil
sirolimus (rapamycin)
SMX
sotalol
spironolactone
stavudine (d4T)
Stimulants
streptokinase
succinylcholine
sucralfate
sulbactam
sulfa-
sulfasalazine
sumatriptan
suramin
tacrolimus
tamoxifen
tamsulosin
tazobactam
terbinafine
terbutaline
tetrabenazine
tetracycline
theophylline
thimine
thiopental
thioridazine
thrombopoietin
tiagabine
ticarcillin
ticlopidine
timolol
tobramycin
tocainide
tolbutamide
topiramate
tPA
tramadol
tranylcypromine
trastuzumab (herceptin)

trazodone
triamterine
triazolam
trifluoperazine
triiodothyronine
trimethoprim
tropicamide
tubocurarine
urokinase
valproate
vancomycin
vardenafil
varenicline
venlafaxine
verapamil (non-DHP)
vigabatrin
vinblastine
vincristine
vitamin A (xs)
vitamin E
vitamin K
warfarin
zalcitabine (ddC)
zaleplon
zanamivir
zidovudine (ZDV)
zileuton
ziprasidone
Zn
zoledronate (IV)
zolpidem
α-methyldopa