P450 interactions up down barbiturates sulfonamides neuro drugs are for phenytoin erythromycin those who act up carbamazepine cimetidine griseofulvin ketoconazole inhibits enzyme ramp up rifampin isoniazid chronic EtOH use acute EtOH use St. John's Wort grapefruit juice quinidine HIV protease inhibitors torsades class III, IA dilated CM doxorubacin (amiodarone), daunarubicin aplastic anemia chloramphenicol, benzene, NSAIDs, propylthiouracil, methimazole, carbamazepine hemolysis in G6PDINH, sulfonamides, antimalarials, aspirin, ibuprofen, nitrofurantoin nephro-/oto-toxic aminoglycosides, cisplatin, vancomycin, loop diuretics disulfiram-like rxn cephalosporins, metronidazole, 1G sulfonylureas (tolbutamide, chlorpropamide), procarbazine ending -afil -ane -azepam -zolam -azine -azole -barbital -caine -cycline -etine -ipramine -navir chloramphenicol, benzene, NSAIDs, propylthiouracil, methimazole, carbamazepine -operidol -oxin -phylline cephalosporins, metronidazole, 1G sulfonylureas (tolbutamide, chlorpropamide), procarbazine -terol -tidine -triptan -triptyline function example erectile dysfunction sildenafil inhalational general anesthetic halothane BDZ diazepam BDZ alprazolam phenothiazine (neuroleptic, antiemetic) chlorpromazine antifungal ketoconazole barbiturate phenobarbital local anesthetic lidocaine protein synth inhibiting abx tetracycline SSRI fluoxetine TCA imipramine protease inhibitor saquinavir butyrophenone (neuroleptic) haloperidol glycoside (inotrope) digoxin methylxnthine theophylline β2 ag albuterol H2 ant cimetidine 5HT1B/1D ag (migrane) sumatriptan TCA amitriptyline Micro Drug Class penicillin B-lactam nafcillin PCNase-resistant dicloxacillin PCN, narrow methicillin spectra ampicillin aminoPCN, wide amoxicillin spectrum ticarcillin extended piperacillin spectrum PCN carbenicillin clavulanic acid B-lactamase sulbactam inhibitor tazobactam cefazolin 1G ceph cephalexin 1G ceph cefoxitin 2G ceph cefalcor 2G ceph cefuroxime 2G ceph ceftriaxone 3G ceph ceftazidime 3G ceph cefipime 4G ceph aztreonam monobactam imipenem/cilastatin carbapenem meropenem carbapenem vancomycin glycopeptide gentamicin AG amikacin AG tobramycin AG neomycin AG tetracycline tetracycline I doxycycline tetracycline demeclocycline tetracycline minocycline tetracycline erythromycin macrolide clarithromycin macrolide azithromycin macrolide chloramphenicol clinda-/linco-mycin lincosamide sulfa- sulfonamide SMX sulfonamide I trimethoprim +SMX nitrofurantoin ciprofloxacin FQ enoxacin FQ metronidazole colistimethane polymyxin dapsone clofazimine rifampin

INH (isoniazid) pyrazinamide ethambutol pentamidine (aerosolized) linezolid quinupristin streptogramin dalfopristin streptogramin amphotericin B

flucytosine nystatin miconazole azole ketoconazole azole fluconazole azole caspofungin terbinafine griseofulvin suramin antiprotozoan melacortin antiprotozoan nifurtimox antiprotozoan Na stibogluconate antiprotozoan chloroquine antiprotozoan mefloquine antiprotozoan quinine antiprotozoan pyrimethamine antiprotozoan mebendazole antihelminth albendazole antihelminth pyrantel pamoate antihelminth ivermectin antihelminth diethylcarbamazine antihelminth praziquantel antihelminth amantidine rimantidine zanamivir oseltamivir palivizumab ribavirin acyclovir famciclovir gangciclovir foscarnet saquiNAVIR protease I indiNAVIR protease I stavudine (d4T) nucleoside zalcitabine (ddC) reverse didanosine (ddI) transcriptase inhibitor zidovudine (ZDV) nevirapine NNRTI efavirenz NNRTI delaviridine NNRTI enfuvirtide fusion inhibitor

IFN-α recombinant

IFN-β recombinant IFN-γ recombinant Immune Drug Class cyclosporine tacrolimus sirolimus (rapamycin) daclizumab azathioprine muromonab-CD3 (OKT-3) aldesleukin recombinant erythropoietin recombinant filgrastim recombinant sargramostim recombinant oprelvekin recombinant thrombopoietin recombinant digoxin immune Fab therapeutic ab Pharm/Cardio Drug Class metyrosine guanethidine bethanechol direct ACh ag neostigmine AChEI edrophonium AChEI pyridostigmine AChEI physostigmine AChEI atropine ACh ant pralidoxime scopolamine ACh ant oxybutynin ACh ant glycopyrrolate ACh ant hexamethonium nicotinic ag epinephrine Symp ag

NE Symp ag DA Symp ag dobutamine Symp ag phenylephrine Symp ag ephedrine cocaine

clonidine α-methyldopa ergonovine phenoxybenzamine phentolamine (praz)-osin carvedilol labetalol nadolol pindolol acebutolol betaxolol propranolol AND class II anti- timolol arrhythmics esmolol atenolol metoprolol hydralazine vasodilator verapamil (non-DHP) (L-type) CCB and type IV diltiazem (non-DHP) antiarrhythmic nife-/amlo-dipine (DHP) (L-type) CCB nitroglycerin venodilator isosorbide dinitrate venodilator nitroprusside fenoldopam diazoxide K-ch opener -statin HMG-CoA RI niacin (also see vitamin B3 section) cholestyramine bile acid resin colesevelam ezetimibe gemfibrozil fibrate digoxin cardiac glycoside class I antiarrhythmics Na ch blockers disopyramide class IA anti- quinidine arrhythmics procainamide mexiletine class IB anti- lidocaine arrhythmics tocainide moricizine/encainide class IC anti- flecainide arrhythmics propafenone sotalol class III anti- ibutilide arrhythmics: K- bretylium channel blockers dofetilide amiodarone

adenosine antiarrhythmic

K antiarrhythmic Mg antiarrhythmic Endocrine Drug Class bromocriptine cabergoline methimazole propylthiouracil octreotide desmopressin (ddAVP) lispro rapid-acting aspart insulin (SPeedy) insulin NPH intermediate glargine long-acting insulin detemir tolbutamide 1G sulfonyl-urea chlorpropamide glyburide 2G sulfonyl-urea glimepiride glipizide metformin biguanide pioglitazone thiazolidine- rosiglitazone diones acarbose α-glucosidase miglitol inhibitor pramlintide amylin mimetic exenatide GLP-1 analog levothyroxine triiodothyronine GH oxytocin hydrocortisone synthetic beclomethasone glucocorticoid dexamethasone prednisone GI Drug Class methscopolamine ACh ant pirenzepine ACh ant propantheline ACh ant famoTIDINE raniTIDINE cimeTIDINE nizaTIDINE omeprazole PPI lansoprazole bismuth sucralfate misoprostol

Al(OH)3 antacid

Mg(OH)2

CaCO3 sulfasalazine etanercept recombinant adalimumab therapeutic ab infliximab therapeutic ab ondansetron metoclopramide

Heme/Onc Drug Class heme and glucose vitamin A (xs) heparin

enoxaparin LMW heparin

(bival)-IRUDIN hirudin warfarin

tPA urokinase streptokinase anistreplase clopidogrel ticlopidine abciximab therapeutic ab

methotrexate (MTX) antimetabolite (all work on S-phase) 5-FU

6-MP 6-thioguanine (6TG) cytarabine (ara-C) dactinomycin antitumor abx (mostly G2) doxorubicin (adriamycin) daunorubicin bleomycin (eto)-POSIDE (VP-16) nitrosurea alkylating agents (-mustines) cyclophosphamide ifosfamide procarbazine busulfan vincristine microtubule vinblastine inhibitor (M- paclitaxel phase) -TAXOLs (cis/carbo)-PLATIN amifostine hydroxyurea (S-phase) trastuzumab (herceptin) therapeutic ab imatinib (Gleevec) NOT AN Ab rituximab therapeutic ab Musculoskeletal Drug Class aspirin (ASA) NSAIDs

ibuprofen naproxen ketorolac indomethacin celecoxib acetaminophen

(etid)-RONATE bisphos-phonates zoledronate (IV) colchicine probenecid allopurinol

Neuro Drug Class riluzole latanoprost brimonidine carbachol direct ACh ag pilocarpine direct ACh ag echothiophate AChEI tropicamide ACh ant morphine opioid, μR codeine opioid heroin opioid meperidine opioid dextromethorphan opioid loperamide opioid diphenoxylate opioid fentanyl opioid methadone opioid enkephalin opioid, δR dynorphin opioid, κR tramadol opioid butorphanol opioid buprenorphine opioid phenytoin also IB anti- arrhythmic fosfentoin parenteral carbamazepine mood stabilizer lamotrigine gabapentin topiramate phenobarbital barbiturate thiopental barbiturate (IV) valproate mood stabilizer ethosuximide tiagabine vigabatrin levetiracetam

MgSO4 triazolam short-acting BDZ oxazepam alprazolam chlordiazepoxide BDZ lorazepam diazepam zolpidem non-BDZ hypnotic zaleplon eszopiclone halothane enflurane methoxyflurane phencyclidine arylcyclo- ketamine hexylamine propofol succinylcholine motor nACh-R blocker tubocurarine pancuronium dantrolene bromocriptine pramipexole ropinirole amantidine levodopa/carbidopa ente-/tol-capone benztropine reserpine tetrabenazine memantine rivastigmine donepezil galantamine sumatriptan

Psych Drug Class thioridazine antipsychotic (typical, neuroleptic) chlorpromazine trifluoperazine fluphenazine haloperidol quetiapine atypical reisperidone antipsycotics aripiprazole ziprasidone clozapine olanzapine lithium mood stabilizer

buspirone amitriptyline tricyclic anti- notriptyline depressants desipramine imipramine clomipramine (par/flu)-oxetine SSRI sertraline citalopram venlafaxine SNRI duloxetine atomoxitene phenelzine MAOI tranylcypromine isocarboxazid selegiline varenicline bupropion atypical anti- mirtazapine depressants maprotiline trazodone methylphenidate CNS stimulant amphetamine dexedrine amphetamine Addiction Drug/Type Withdrawal Depressants anxiety, tremor, seizures, insomnia acute EtOH severe: DT (life threatening, peaks 2-5d after last drink, ANS chronic EtOH hyperactivity [tachycardia, seizures], psychosis, confusion) Stimulants crash, depression, lethargy, wt gain, headache caffeine nicotine irritability, anxiety, craving Hallucinogens PCP depression, anxiety, irritability, restlessness, anergia, thought/sleep disturbances LSD marijuana irritability, depression, insomnia, N, anorexia; peak in 48h, last up to 7days; can be detected in urine for up to 1 month Renal Drug Class mannitol acetazolamide ethacrynic acid loop diuretic furosemide hydrochlorothiazide thiazide eplerenone K-sparing diuretics spironolactone triamterine amiloride captopril ACEI lisinopril enalapril Repro Drug Class leuprolide GnRH ag methyltestosterone

finasteride flutamide ethinyl estradiol estrogen mestranol diethylstilbestrol clomiphene SERM tamoxifen raloxifene HRT exemestane anastrozole progestin mifepristone (RU-486) dinoprostone terbutaline Symp ag ritodrine tamsulosin sildenafil vardenafil Respiratory Drug Class diphenhydramine 1G H1 blockers chlorpheniramine loratadine 2G H1 blockers fexofenadine desloratadine certirizine methacholine direct ACh ag ipratropium ACh ant isoproterenol Symp ag metaproterenol Symp ag albuterol salmeterol theophylline methylxanthine cromolyn zileuton antiLT (zafir)-lukast guaifenesin N-acetylcysteine bosentan Biochem Name Vitamin retinol A

calcitriol (D3) D vitamin E E vitamin K K thimine B1

riboflavin B2 niacin B3 pantothenate B5 pyridoxal P B6 cobalamin B12

folate

biotin (B7) ascorbic acid C

Zn

Toxins/Antidotes drug class salicylate iron (hemochromatosis) lead mercury arsenic gold copper (Wilson's) cyanide methemoglobin CO methanol ethylene glycol benzene ouabain Amanita phalloides (poison mushroom) antimycin A rotenone oligomycin 2,4-DNP organophosphates Micro Use GP (not Staph), Syph

S. aureus (not MRSA)

certain GPs (Listeria, enterococci) and GNRs (Proteus, H. flu, E. coli, Salmonella) Pseudomonas (+AG) and GNR Pseudomonas (+AG) and GNR Pseudomonas (+AG) and GNR

GPC, Proteus, E. coli, K. pneumo (think UTI)

GPC, Proteus, E. coli, K. pneumo, H. flu, Enterobacter, Neisseria, Serratia (think more UTIs, gonorrhea) H. flu meningitis, Neisseria, gonorrhea prophylaxis

Pseudomonas Pseudomonas and GP GNRs ONLY, synergistic w/ AGs

GPC, GNR, anaerobes; broad spectrum, B- lactamase resistant GPs ONLY, esp MDR (MRSA, Enterococci, and C. diff) GNR, synergistic w/ B-lactams GNR, synergistic w/ B-lactams GNR, synergistic w/ B-lactams bowel surgery intracellulars: B. burgdorferi, H. pylori, M. pneumo, Rickettsia, Chlamydia (no CNS penetration)

+ADH antagonist (diuretic in SIADH) +meningococcal prophylaxis (2nd line) atypical pneumonia (Legionella, M. pneumo, Chlamydia), URI, STD, cocci (GP/Neisseria) + MAC prophylaxis (AIDS) meningitis (H. flu, N. meningitides, S. pneumo) anaerobes in aspiration pneumonia GP, GN, Nocardia, Chlamydia +UTI

UTIs (tx or prophylactic for recurrent), Shigella, Salmonella, PCP (tx/prophylaxis) UTIs (esp E. coli), used in pregnancy GNR (esp of UTI/GI infxn), Neisseria, some GPs

GI protozoa (Giardia, Entamoeba), vaginal (Trichomonas, Gardnerella), anaerobes resistant GNs M. leprae (oral, long term), PCP M. leprae (added to dapsone) M. leprae (delays resistance to dapsone), prophylactic for H. flu and N. meningitides; M. TB (quad tx) M. TB (quad tx and prophylaxis)

M. TB (quad tx) M. TB (quad tx) PCP (prophylaxis, second line, after bactrim) VRE VRE VRE serious systemic mycoses: Histoplasma, Blastomyces, Coccidioides, Aspergillus, Candida, Mucor systemic infxn along with Amphotericin B Candida (thrush, diaper rash, vaginal) topical (esp tinea) Candida, Histoplasma, Blastomyces, PCOS (hirsutism), Coccidioides, hypercortisolism Cryptococcal meningitis in AIDS, Candida Invasive Aspergillosis dermatophytes (esp onychomycosis) oral tx of superficial infxn, esp dermatophytes (tinea, ringworm) Trypanosomes, no CNS penetration Trypanosomes, CNS penetration T. cruzi Leishmaniasis Plasmodium Plasmodium (resistant to chloroquine) chloroquine-resistant Plasmodium (+ pyrimethamine and sulfonamide); Babesia P. falciparum, + sulfadiazine=toxo GI, neurocysticercosis Echinococcus Enterobius, Ascaris, hookworms Onchocerca, Strongyloides Loa loa, Wuchereria bancrofti, Toxocara canis tapeworms and flukes Influenza A (tx and prophylaxis), Parkinson's dz

influenza A and B

RSV RSV, chronic hep C HSV (tx and prophylaxis), VZV, EBV herpes zoster CMV (mostly in immunocompromised) gangciclovir-resistant CMV retinitis, acyclovir- resistant HSV HIV HIV HIV HIV HIV HIV (tx, prophylaxis, pregnancy) HIV HIV HIV HIV (used in pts w/ persistent viral replication despite HAART) chronic hep B/C, Kaposi's sarcoma, leukemias, malignant melanoma MS NADPH oxidase deficiency Immune Mechanism Binds cyclophilins, inhibits calcineurin preventing IL-2 and IL-2R production Binds FK-BP, inhibits IL-2 and IL-2R production (and other cytokines) inhibits mTOR and TC response to IL-2 MAb w/ high affinity for IL-2R on activated TC antimetabolite precursor to 6-MP (interferes w/ nucleic acid synth) MAb that binds CD3 (epsilon chain) on TC, blocks signal transduction IL-2 epoetin Granulocyte Colony Stimulating Factor Granulocyte/Macrophage-CSF IL-11 thrombopoetin

Pharm/Cardio Mechanism inhibits tyrosine hydroxylase (makes DOPA) inhibits NE release (replaces it in vescicles) ACh ag, resistant to AChE no CNS penetration no CNS penetration, extremely short acting no CNS penetration, long acting CNS penetration regenerates AChE regenerates AChE CNS GU ganglionic blocker vasoconstriction decreases aq humor production; low dose: β>α; high: α>β α>β1 D>β>α, inotropic and chronotropic β1>β2, inotropic α1>α2 release stored catecholamines catecholamine reuptake inhibitor, inactivates Na channels central α2 ag, decrease central adrenergic outflow peripheral alpha agonist (and DA, 5HT) irreversible nonselective α-blocker reversible nonselective α-blocker α1-blocker (smooth m relaxation) nonselective α- and β-blocker nonselective α- and β-blocker nonselective β-blocker nonselective partial β-agonist β1 partial agonist (>β2) selective β1-blocker nonselective β-blocker nonselective β-blocker selective β1-blocker, short-acting selective β1-blocker selective β1-blocker increased cGMP, relaxing smooth m; arterioles>veins, afterload reduction reduce mm contractility, ventricle>>vessels; β- blocker-like antianginal reduce mm contractility, ventricle=vessels vasodilator, ventricle<aa, decrease preload short acting, same as nitroglycerin D1 ag, relaxes renal vascular smooth m hyperpolarizes/relaxes vascular smooth m inhibits chlsl to mevalonate decreases hepatic VLDL secretion into circ, inhibit lipolysis in adipose tissue prevents intestinal reabs of bile acids, liver uses chlsl to make more prevents chlsl reabs at small intestine brush upregulate LPL causing increased TG Cl. inhibition of Na/K ATPase causes indirect inhibition of Na/Ca exchanger, increases [Ca]i, positive inotropy; stimulates vagus (suppresses AV node) affect on AP: phase 1=BAC (B is unchanged); phase 3=BCA (C is unchanged) increase AP duration, effective refractory period, and QT; big gap in phase 3 from normal; intermediate dissociation speed decrease AP duration (no effect on QRS), preferentially target ischemic/depolarized Purkinje/ventricular tissue; fast dissociation no effect on AP duration, slow dissociation, so significantly prolongs refractory period in AV node increase AP duration, increased effective refractory period, and increased QT interval; big gap in phase 3 from normal; sotalol is also mild beta blocker

transient AV block (A1R=Gq); endothelial dependent smooth m relaxation depress ectopic pacemakers in hypokalemia

Endocrine Mechanism DA ag, inhibits PRL secretion DA ag, inhibits PRL secretion inhibits peroxidase-coupling of MIT/DIT and thyroid hormone synthesis somatostatin analog (in stomach, inhibit ECL cell secretion of histamine) ADH analog; releases endothelial vWF store bind insulin receptor; liver: increased glycogen synthesis; muscle: increased glycogen and protein synthesis, K uptake; fat: aids TG storage

close K-channel in β-cell membrane, causes cell depolarization and triggers Ca influx and insulin release

decreases gluconeogenesis, increase glycolysis and peripheral glucose uptake increase peripheral insulin sensitivity, binds PPAR- γ inhibit intestinal brush border enzymes, delays sugar hydrolysis/absorption decrease glucagon increse insulin, decrease glucagon thyroxine replacement hormone replacement hormone replacement inhibits virtually all cytokines by inactivating NF- κB (TNF-α transcription factor)

+ triggers apoptosis GI Mechanism block M1R on ECL cells (decrease histamine) and M3R on parietal cells (decrease H secretion) reversible block of H2R on gastric parietal cells causes decreased H secretion (cimetidine=also antiandrogenic) irreversibly inhibit H/K ATPase in parietal cells bind to ulcer base, provides physical protection, allows HCO3 secretion

PGE1 analog, increased production of gastric mucous, decreased H+ production can affect absorption, bioavailability, and excretion of other drugs (alters pH or delaying gastric emptying) sulfa- antibiotic + 5-aminosalicylate (anti- inflammatory), activated by bacteria form of TNF-R (sequesters TNF) anti-TNF-α anti-TNF-α

5HT3 ant, powerful central antiemetic

D2R ant causes increased LES tone, motility, contractility, decreased pyloric S tone Heme/Onc Mechanism inhibits ALA synthase (RLS of heme synth) for PML: inhibits retinoic acid receptor causing promyelocyte differentiation activates antithrombin, acts most on Xa and thrombin; very short t1/2; watch PTT acts more on Xa, better bioavailability, longer t1/2; subQ, fine if unmonitored directly inhibit thrombin inhibit activation (γ-carboxylation) of vit K- dependent facotrs (II, VII, IX, X, proteins C and S) convert plasminogen to plasmin, which degrades fibrinogen and fibrin bind w/ plasminogen, activate plasminogen streptokinase bound to plasminogen binds ADPR on platelets, inhibits GpIIb/IIIa expression, inhibits fibrinogen binding GpIIb/IIIa Ab for activated platelets

folic acid analog, inhibits DHFR, decreasing dTMP and DNA/protein synth pyrimidine analog, activated to 5F-dUMP, covalently binds DHFR, which inhibits thymidylate synthase, decreasing dTMP purine analog, inhibits de novo purine synth, activated by HGPRT pyrimidine analog, inhibits DNA Pol intercalates in DNA anthracyclines: noncovalently intercalate in DNA causing breaks; generate free radicals free radical formation, breaks DNA inhibits topoisomerase II (S and G2) require bioactivation, cross BBB covalently cross-link DNA at guanine N7, require activation by liver alkylates DNA alkylates DNA bind tubulin, block polymerization, inhibit mitotic spindle formation hyperstabilize polymerized microtubules, inhibit mitotic spindle degradation cross-link DNA cytoprotective free radical scavenger ribonucleotide reductase inhibitor Ab against HER-2 (erb-B2); possibly kills through Ab-dependent cytotoxicity bcr-abl tyrosine kinase inhibitor Ab against CD-20 (on most BC neoplasms) Musculoskeletal Mechanism irreversibly acetylates COX (1 and 2), prevents conversion of AA to TXA2, PGE2, PGI2

reversibly inhibit COX (1 and 2), blocks prostaglandin synthesis; COX-1 maintains gastric mucosa, COX-2 in inflammatory cells and vascular endothelium reversibly inhibit COX-2 reversibly binds COX, mostly in CNS (peripherally inactivated) inhibits osteoclast activity, reduce resorption + formation of hydroxyapatite binds and stabilizes tubulin, impairing chemotaxis and degranulation inhibits reabsorption of uric acid in PCT, inhibits secretion of PCN inhibits xanthine oxidase, decreased conversion of xanthine to uric acid Neuro Mechanism decreases presynaptic glutamate release

PGF2a (increases outflow of aq humor) α ag (think clonidine) contract ciliary m, increase aq humor outflow + AChE resistant, more potent CNS penetration in eye decrease synaptic transmission by opening K-ch and closing Ca-ch; inhibits release of ACh, NE, 5HT, glu, substance P; induces NO synthase expression, lowers preload decrease synaptic transmission by opening K-ch and closing Ca-ch; inhibits release of ACh, NE, 5HT, glu, substance P; induces NO synthase expression, lowers preload

very weak opioid, SNRI opioid, partial agonist at μ-R, agonist at κ-R opioid, partial ag increased Na channel inactivation (increased refractory period), inhibits presynaptic excitatory glutamate release increased Na channel inactivation blocks voltage-gated Na channels CCB (designed as GABA analog) blocks Na channels, propagates GABA action propagates GABAA action by increasing duration Cl channel is open high potency, highly lipid soluble; decreases cerebral blood flow increased Na channel inactivation, increase GABA concentration blocks thalamic T-type Ca channels inhibit GABA reuptake irreversibly inhibit GABA transaminase unknown increase frequency of Cl channel opening causing propagation of GABAA action; decrease REM

act via BZ1 receptor subtype; reversed by flumazenil unknown; high blood solubility=slower induction and recovery time; high lipid solubility=high potency=lower MAC (aka PCP) blocks NDMA-R

potentiates GABAA phase I=prolonged depol (no antidote, potentiated by neostigmine); II=repol but blocked (antidote=neostigmine) compete for AChRs, reversible w/ cholinesterase inhibitors prevents release of Ca from sarcoplasmic reticulum of skeletal mm (uncoupled) DA ag (ergot derivative) DA ag (non-ergot derivative, so preferred) increases DA release converted to DA in CNS; carbidopa= peripheral dopa-decarboxylase inhibitor COMTI antimuscarinic (atropine) inhibits DA, NE, and 5HT into vescicles (amine depleting) amine depleting (DA) NMDA-R ant (prevent excitotoxicity) AChEI

5HT1B, 1D ag causes vasoconstriction, inhibits V activation and VIP release Psych Mechanism block D2R, but can also block muscarinic, α, and histamine receptors, all low potency; highly lipid soluble (long t1/2) block D2R, high potency; highly lipid soluble (long t1/2) block 5-HT2, DA, α, and H1 receptors unknown (maybe inhibits PI3 cascade), ADH antagonist; exclusively excreted by kidneys, most reabsorbed at PCT with Na

5HT1A agonist SNRI-like mechanism; amitriptyline=3° (most anticholinergic); notriptyline=2° (least anticholinergic)

usually takes 2-4 weeks for antidepressant effects

5-HT>NE reuptake inhibitor 5-HT

selective MAO-BI (main metabolyzer of DA) nAChR partial agonist increased NE and DA

5HT2&3 and α2-blocker (increased NE and DA) blocks NE reuptake blocks 5HT reuptake release stored catecholamines

Addiction Withdrawal anxiety, tremor, seizures, insomnia severe: DT (life threatening, peaks 2-5d after last drink, ANS hyperactivity [tachycardia, seizures], psychosis, confusion) crash, depression, lethargy, wt gain, headache irritability, anxiety, craving depression, anxiety, irritability, restlessness, anergia, thought/sleep disturbances irritability, depression, insomnia, N, anorexia; peak in 48h, last up to 7days; can be detected in urine for up to 1 month Renal Mechanism osmotic diuretic carbonic anhydrase inhibitor phenoxyacetate derivative, same as Lasix inhibit cotransport of NaK2Cl; lose hyper-tonicity of medulla, increase Ca excretion inhibit NaCl reabs in distal tubule, low Ca excretion competitive aldoR ant + mild testosterone R ant block ENaC in DCT inhibit inactivation of bradykinin (vasodilator); causes renin release by loss of feedback inhibition Repro Mechanism pulsatile=agonist, continuous=antagonist T agonist at androgen receptors

5α-reductase inhibitor, lower DHT nonsteroidal competitive T-receptor ant Estrogen receptor antagonist

inhibits negative feedback on hypthalamus ag: bone, endometrium; antag: breast ag: bone; antag: endometrium, breast

aromatase inhibitor reduce growth and vascularization of endometrium competitive progesterone inhibitor PGE2 analog (dilation, uterine contraction) β2

α1A,DR ant (on prostate, α1BR on vessels) inhibit cGMP PDE5I

Respiratory Mechanism reversible inhibitors of H1 histamine R

inhaled, causes bronchoconstriction competitive block of MACh-R β selective β2 ag (β2>>β1)

PDEI (decreases cAMP hydrolysis) stabilizes mast cell granules 5-lipoxygenase inhibitor (AA to LTs) LT receptor antagonist mucolytic, glutathione precursor endothelin-1 receptor antagonist (lower PVR) Biochem Function antioxidant, used in vision pigment, cell differentiation (tx AML M3), also used to treat measles increase intestinal absorption of Ca and PO4 antioxidant (RBCs and cell membranes) catalyzes γ-carboxylation of glutamate on clotting factors (II, VII, IX, X, protein C, S) cofactor for PDH, α-KGDH, transketolase (HMP shunt), branched chain AA DH cofactor in redox (FADH2) made from tryptophan and B6

CoA (acyl transfers and FA synth) used in a ton of rxns (make niacin from trp); deficiency caused by INH, OCPs homocysteine methyltransferase (regeneration of methionine after SAM) and methylmalonyl-CoA mutase (generation of succinyl CoA from catabolism) cofactor nucleic acid synth, methyl transfers (SAM); most common deficiency in US (alcoholics and pregnancy) cofactor for carboxylations (pyruvate, acetyl-CoA, propionyl CoA) antioxidant, facilitates Fe absorption, collagen synthesis, DA to NE essential for 100+ enzymes, transcription factors (Zn fingers) Toxins/Antidotes antidote NaHCO3 (alkalinize urine), dialysis deferoxamine 1st line: CaEDTA and dimercaprol, 2nd: penicillamine; succimer for kids dimercaprol (BAL), succimer dimercaprol (BAL), succimer, penicillamine penicillamine nitrite, hydroxocobalamin, thiosulfate methylene blue, vitamin C 100% O2, hyperbaric O2 ethanol, fomepizole, dialysis

atropine Micro Mechanism Bind PBP, inhibit transpeptidase cross-linking of cell wall, and activate autolytic enzymes Same as PCN, but bulkier R group

Same as PCN, wider spectrum, PCNase sensitive (use with clavulanic acid) Same as PCN, PCNase sensitive (use with clavulanic acid)

B-lactam, but less susceptible to PCN-ases, bactericidal

for serious gram negative infxn

inhibits cell wall synth (binds PBP3), B-lactamase- resistant, synergistic w/ AGs cilastatin=renal dehydropeptidase I inhibitor, decreases inactivation of drug; seizures, GI distress, rash dehydropeptidase I stable, lower risk of seizures; GI distress, skin rash inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of precursors bind 30S, inhibit initiation complex, cause misreading of mRNA; require O2 for uptake (no anaerobes); modifying transferase enzymes (acetylation, eg) can lead to resistance binds 30S and prevents attachment of AA-tRNA; resistance by decreased uptake or increased efflux by pumps (plasmid-encoded); do not take w/ milk, antacids, or Fe (divalent cations inhibit absorption) binds 23S or 50S and inhibits translocation

inhibits 50S peptidyltransferase; plasmid-encoded acetyltransferase inactivates drug binds 50S and inhibits translocation PABA antimetabolytes inhibit DHpteroate synthetase (DHpteroate=DHF precursor); resistance=all mechanisms bacterial DHFRase I

bacterial DNA damage topoisomerase II inhibitor; resistance=mutated DNA gyrase; do not take w/ antacids free radical toxic metabolites that damage DNA

disrupts membranes (basic cations=detergent)

DNA-dep RNA pol inhibitor

decreased synth of mycolic acid, activated by bacterial catalase-peroxidase

binds 50S and inhibits translocation

binds ergosterol, forms pores in membrane; does not cross BBB (intrathecal for meningitis)

converted to 5-FU, inhibits DNA synth same as amphotericin B inhibit fungal ergosterol synthesis by inhibiting P450 enzyme (lanosterol 14-α-demethylase); for systemic mycoses; ketoconazole also inhibits human enzyme desmolase (T-synth) β-glucan cell wall synthesis inhibitor squaline epoxidase I (ergosterol precursor) microtubule inhibitor, deposits in keratin-containing tissues inhibits energy metabolism enzymes inhibits sulfhydryl enzymes forms intracellular oxygen radicals inhibits glycolysis at PFK blocks plasmodium heme polymerase (buildup of toxic hemoglobin products) chloroquine-resistant Plasmodium (+ pyrimethamine and sulfonamide); Babesia inhibits plasmodial DHFRase inhibits glucose uptake and microtubule synth inhibits glucose uptake and microtubule synth stimulates depolarization-induced paralysis by stimulating nicotinic receptors at NMJ amplifies GABA-mediated inhibition leading to immobilization; doesn't cross BBB (no effect on humans) increases membrane permeability to Ca (contraction, paralysis) blocks viral penetration/uncoating (M2); also causes release of DA from intact nerves; resistance=mutated M2 (90% of flu A resistant) inhibit neuraminidase neutralizes F-protein inhibit IMPDH (guanine synthesis) guanosine analog: monophosphorylated by viral thymidine kinase, triphosphate made in human cells; leads to chain termination viral DNA pol inhibitor, binds to PP-binding site, no activation required prevents cleavage of polypeptide products of pol gene, thus inhibiting virion assembly competitively inhibit nucleotide binding site on RT causing DNA chain termination; must be activated first by viral thymidine kinase bind to RT at site different from NRTIs, do not require phosphorylation bind gp41: inhibit conformational change necessary for fusion with CD4 cells synthesized by viral infected cells to block replication of DNA and RNA viruses

Immune Use some autoimmune disorders, suppresses organ rejection suppresses organ rejection (very strong immunosuppressant) kidney transplant (+ cyclosporine and steroids) kidney transplant kidney transplant, autoimmune disorders (including GN, hemolytic anemia, UC) kidney transplant

RCC, metastatic melanoma anemias (esp renal failure) bone marrow recovery bone marrow recovery thrombocytopenia thrombocytopenia antidote for digoxin intoxication Pharm/Cardio Use htn from pheo (prevents catecholamine synth) htn neurogenic ileus/urinary retention and postop neurogenic ileus/urinary retention and postop (reversal of NMJ block), myasthenia gravis dx of myasthenia gravis tx of myasthenia gravis glaucoma and atropine OD causes mydriasis and cycloplegia, tx of ACh poisoning (organophosphates) with atropine, for cholinesterase poisoning motion sickness reduce urgency in mild cystitis and reduce bladder spasms used in experiments only anaphylaxis, open angle glaucoma, asthma, hypotension hypotension (but decreases renal perfusion) shock (increases renal perfusion), CHF CHF, cardiac stress testing pupillary dilation, vasoconstriction, nasal decongestion nasal decongestant, urinary incontinence, hypotensio causes vasoconstriction, local anesthesia

htn, esp. in renal disease (no decrease in renal blood flow), DM, 1st line in preg (+ hydralazine) dx of Prinzmetal's angina, placental delivery pre-op on pheo htn, urinary retention in BPH htn (decrease CO, decrease renin secretion [β blockade on JGA cells]), angina (decrease afterload, decrease HR and contractility [via calcium channels] causing decreased O2 consumption), MI and CHF (decrease mortality [esp carvedilol], slow progression), glaucoma (timolol, carve-dilol, betaxolol, decrease secretion of aqueous humor), antiarrhythmics (SVT, VT, AFib; decrease cAMP, Ca currents, and AV conduction velocity, increase PR); headache, essential tremor (propranolol)

htn in pregnancy (1st line, with methyldopa), severe htn, CHF htn, angina (no unstable for DHP), Raynaud's, arrhythmias (non-DHPs; nodal arrhythmias [SVT, AFib]: slow conduction velocity, increase refractory period and PR, decrease slope of phases 1 and 2) angina, pulmonary edema, aphrodisiac, erection enhancer, esophageal spasm malignant htn malignant htn malignant htn, insulinoma lower LDL>>TG, raise HDL a little lower LDL>TG, raise HDL a bunch lower LDL, slightly raise HDL and TG lower LDL lower TG>>>LDL, raise HDL a little CHF (decrease morbidity, not mortality), AFib (depresses SA node, slow AV nodal conduction);

75% bioavailable, 20-40% protein bound, t1/2=40h, urinary excretion mnemonic: Double Quarter Pounder, Lettuce Tomato Mayo, Extra/More Fries Please good for atrial and ventricular arrhythmias, especially reentrant and ectopic SVT, and VT acute ventricular arrhythmias (esp post-MI) and digitalis-induced arrhythmias (lidocaine)

VT (esp that go to VFib), intractible SVT, last resort in refractory tachyarrhythmias, only in pts w/o structural abnormalities used when other arrhythmics fail; amiodarone has class I, II, III, and IV effects bc it alters the lipid membrane

dx/tx of SVT, dx of CAD, very short acting (~15s) digoxin toxicity torsades and digoxin toxicity Endocrine Use PRLoma, Parkinsons, neuroleptic malignant sz PRLoma hyperthyroidism

GHoma, NET, gastrinoma, glucagonoma, acute variceal bleed, VIPoma, carcinoid tumor central DI, von Willebrand's dz DM, gestational DM, life-threatening hyperkalemia, stress-induced hyperglycemia

T2DM (stimulates endogenous release of insulin, need some β-cell function, so useless in T1DM)

oral, can be used in pts w/o islet function (T1 or 2DM) T2DM (monotherapy or combo)

T2DM (monotherapy or combo)

T2DM T2DM hypothyroidism, myxedema

GH deficiency, Turner's stimulates labor, uterine contractions, milk let-down, controls uterine hemorrhage Addison's, inflammation, immune suppression (Crohn's), asthma (1st line for chronic) + dx of Cushing's dz (suppression test) + CLL, Hodgkins GI Use peptic ulcers (rarely used)

PUD, gastritis, mild esophageal reflux

PUD, gastritis, esophageal reflux, Zollinger-Ellison Sz, H. pylori (+ clari, metro/amoxi) improved ulcer healing, traveller's diarrhea, + metronidazole + amoxicillin (or tetracycline) for H. pylori prevention of NSAID-induced ulcer, induce labor, maintenance of ductus arteriosus all cause hypokalemia

UC, Crohn's

Crohn's, RA, psoriatic arthritis Crohn's, RA, psoriatic arthritis Crohn's, RA, psoriatic arthritis, ankylosing spondylitis decrease vomiting (post-op, chemo) antiemetic, gastroparesis (DM or post-surgery), does not influence colon transport time Heme/Onc Use acute intermittent porphyria acne, measles, PML (AML M3) immediate anticoagulation: PE, CVA, acute coronary sz, MI, DVT; safe for pregnancy

heparin alternative in pts w/ hx of HIT chronic anticoagulation, oral

early MI, early ischemic stroke

acute coronary sz, coronary stenting, decrease risk of thrombotic stroke prevent cardiac ischemia in unstable angina and in pts txed w/ percutaneous coronary intervention, acute coronary sz leukemia, lymphoma, chorioca, sarcomas; abortion, ectopic pregnancy, RA, psoriasis solid tumors, topical for basal cell ca, synergistic w/ MTX leukemia or lymphoma (not CLL or HL), UC ALL AML, ALL, high grade NHL Ewing's sarcoma, rhabdomyosarcoma, childhood tumors (Wilm's) Hodgkins, myelomas, sarcomas, solid tumors

testicular and Hodgkins SCC of lung/prostate, testicular brain tumors (including glioblastoma multiforme)

NHL, breast, ovarian; also good immunosuppressants

Hodgkin's, brain tumors CML, pre-marrow-transplant marrow ablation Hodgkins, Wilm's, chorioca ovarian and breast testicular, bladder, ovary, lung prevent nephrotoxicity and xerostomia, given with platinum and alkylating agents melanoma, CML; sickle-cell (increase HbF) HER-2-overexpressing breast cancer

CML (Philadelphia chr., main target), GIST BC non-Hodgkin's lymphoma, RA (+ MTX) Musculoskeletal Use low dose (<300mg/day, TXA2): antiplatelet; intermed dose (300-2400mg/day, PGE2): antipyretic and analgesic; high dose (2400-4000mg/day): anti- inflammatory antipyretic, analgesic, anti-inflammatory, acute gout (w/ colchicine, esp indomethacin), migranes

+ induces closure of PDA, nephrogenic DI RA, OA, pts w/ gastritis/ulcers antipyretic, analgesic, NO anti-inflammatory

malignancy-associated hypercalcemia, Paget's dz of bone, postmenopausal osteoporosis acute gout (with NSAIDs, esp indomethacin)

chronic gout, also given w/ PCN to prolong t1/2 chronic gout; lymphoma/leukemia w/ chemo to prevent tumor lysis urate nephropathy Neuro Use ALS glaucoma glaucoma glaucoma, causes miosis, relieve IOP glaucoma emergency, ups sweat, tears, saliva glaucoma causes mydriasis and cyclopegia pain, acute pulmonary edema

+ cough suppression + diarrhea (no CNS sfx) + diarrhea (CNS sfx) (stronger than morphine) (partial ag, long acting) heroin detox endogenous endogenous chronic pain pain pain, opioid addiction, used w/ naloxone seizures (all but absence), first line for tonic clonic or status seizure prophylaxis, arrhythmias (IB) partial, tonic clonic (1st line), trigeminal neuralgia (1st line), bipolar partial and tonic clonic partial and tonic clonic, peripheral neuropathy, bipolar partial and tonic clonic partial + tonic clonic (esp in pregnancy/kids), anxiety, insomnia, Crigler-Najjar Sz type II induction of anesthesia (decrease cerebral blood flow) seizures (all but status, first line in tonic clonic), myoclonic seizures, bipolar absence (first line) partial seizures partial seizures partial and tonic clonic eclamptic seizures (1st line), torsades anxiety, panic disorder, GAD, detox (esp EtOH withdrawal and DT), cocaine OD, night terrors, sleepwalking, insomnia, general anesthetic, spasticity + acute status epilepticus (first line) or eclamptic seizures (after MgSO4) insomnia inhaled anesthetic (increase cerebral blood flow, depress CV/resp) dissociative anesthetic rapid anesthesia induction depolarizing paralytic (for pts on a mechanical vent or during surgery) non-depolarizing paralytic malignant hyperthermia and neuroleptic malignant syndrome, mm relaxant Parkinson , PRLoma, neuroleptic malignant sz Parkinson

Parkinson; influenza A, rubella Parkinson (ODISIA)

Parkinson (tremor and rigidity, not bradykinesia) Huntington (also haloperidol to tx)

Alzheimer's ("GRiM Dz")

Migrane, cluster headache; short t1/2 (<2h)

Psych Use schizophrenia (mostly positive sx), psychosis, mania (acute), Tourette's (esp haloperidol)

+ Huntington schizophrenia (positive and negative sx)

+ OCD, anxiety, depression, mania, Tourette's bipolar, blocks relapse and acute manic events; SIADH

GAD, anxiety major depression, fibromyalgia, panic disorder

+ bedwetting (decreases stage 4 sleep) + OCD OCD, social phobia, specific phobia, panic disorder, PTSD, GAD, anorexia/bulimia, anxiety, depression (typical or atypical) depression, GAD depression, diabetic peripheral neuropathy ADHD atypical depression, anxiety, hyperchondriasis

+ Parkinson (use w/ L-dopa) smoking cessation bipolar, depression, smoking cessation bipolar, depression + insomnia bipolar, depression insomnia, depression (very high doses) narcolepsy, obesity, ADHD

ADHD Addiction Intoxication mood elevation, decreased anxiety, sedation, behavioral disinhibition, respiratory depression emotional lability, ataxia, coma, serum GGT (sensitive EtOH use), AST>2*ALT; acute EtOH=P450 down; chronic EtOH=P450 up, gynecomastia; assn w/ periventricular hemorrhage/necrosis of mammillary bodies mood elevation, psychomotor agitation, insomnia, arrhythmias, tachycardia, anxiety restlessness, diuresis, muscle twitching restlessness homocidality, delerium, belligerence, fever, nystagmus, tachycardia, psychomotor agitation, impulsiveness flashbacks, pupillary dilation, marked anxiety/depression, delusions, visual hallucinations paranoid delusions, slowed time perception, social withdrawal, dry mouth, hallucinations

Renal Use shock, drug OD, increased ICP/IOP urinary alk (TCA/bartbiturate/salicylate OD, cystinuria), MAlk, altitude sickness, glaucoma diuresis in sulfa-allergies or gout pts edema (CHF, cirrhosis, nephrotic sz, pulmonary edema), htn, hypercalcemia htn, CHF, idiopathic hypercalciuria, nephrogenic DI hyperaldo, K-depletion, CHF, hirsutism (spironolactone)

+ nephrogenic DI htn, CHF, diabetic renal dz Repro Use infertility, prostate ca (+ flutamide), fibroids hypogonadism, develop 2° sex characteristics, burn pts (promotes anabolism)

BPH, male pattern baldness prostate cancer (+ leuprolide) hypogonadism, POF, menstrual abnormailities, postmenopausal HRT, androgen-dependent prostate cancer ovulation induction breast cancer (ER-positive), prevent osteoporosis menopausal sx (hot flashes, vaginal atrophy, osteoporosis [E2 decreases osteoclast activity]) ER-positive breast cancer in postmenopausal women oral contraceptives, endometrial cancer, abnormal uterine bleeding pregnancy termination (+ misoprostol) labor inducer reduce premature uterine contractions

BPH (inhibits only prostatic smooth m) ED

Respiratory Use allergy, motion sickness, sleep aid allergy

challenge test for dx of asthma asthma, COPD lowers BP (not used), asthma acute asthma acute asthma long term asthma (attack prophylaxis) asthma, adenosine toxicity only for asthma/allergy prophylaxis, not tx asthma asthma (especially aspirin-induced) expectorant loosen plugs (CF), acetaminophen OD pulmonary htn Biochem Deficiency nyctalopia (night blindness), dry skin

rickets (kids), osteomalacia, hypocalcemic tetany, breast milk is low in vitamin D hemolytic anemia, mm weakness, posterior column and spinocerebellar demyelination neonatal hemorrhage w/ increased PT and PTT, normal bleeding time; warfarin, cephalosporin Wernicke-Korsakoff or Beriberi (wet=dry + high output cardiac failure; dry=polyneuritis, symmetrical mm wasting); glucose can worsen cheilosis (inflammation of lips), corneal vascularization glossitis; severe=pellagra (diarrhea, dermatitis [Casal's collar], dementia) dermatitis, enteritis, alopecia, adrenal insuff convulsions, hyperirritability, peripheral neuropathy, sideroblastic anemia, pellagra megaloblastic anemia, hypersegmented PMNs, neuro sx; from malabsorption in terminal ileum (Crohn's, sprue, enteritis, D. latum) or lack of intrinsic factor (PA, gastric bypass) megaloblastic anemia, no neuro sx, but teratogenic (neural tube defects); can be from drugs (phenytoin, MTX, sulfonamides) dermatitis, alopecia, enteritis; rare: excessive ingestion of raw eggs (avidin) or abx use scurvy: swollen gums, bruising, hemarthrosis, anemia, poor wound healing, weak immune poor wound healing, hypogonadism, decreased adult hair, dysgeysia, anosmia, risk of cirrhosis Toxins/Antidotes SFX/other not for gout (need too high of a dose) acute: gastric bleeding; chronic: MAc, GI scarring 1st line: CaEDTA and dimercaprol, 2nd: penicillamine; succimer for kids

vomiting, rice water stool, garlic breath; SqCC can be from nitroprusside (tx for malignant htn) created by nitrite bc it binds CN strongly

aplastic anemia hepatotoxicity/necrosis Micro SFx/Other bacteriocidal; G=IV, V=oral; can cause hypersensitivity rxn (all PCNs) or hemolytic anemia, SJS same as PCN

+ interstitial nephritis pseudomembranous colitis + higher oral availability; rash

Hypersensitivity (cross hypersensitivity with PCNs in 5-10%), vitamin K deficiency, disulfiram-like rxn with EtOH (only in some cephalosporins), increase nephrotoxicity of aminoglycosides

no cross-allergenicity w/ PCN or cephalosporins, good in renal insufficiency; occasional GI upset cilastatin=renal dehydropeptidase I inhibitor, decreases inactivation of drug; seizures, GI distress, rash dehydropeptidase I stable, lower risk of seizures; GI distress, skin rash rarely SFx: nephrotoxicity + ototoxicity, thrombophlebitis, "red man syndrome" (preventable by slow infusion) nephrotoxic (especially when used w/ cephalosporins), ototoxic (especially when used w/ loop diuretics), teratogenic (CN VIII agenesis)

GI distress, teratogen (teeth discoloration), bone growth inhibition in kids, hypersensitivity; expired causes Fanconi's, photosensitivity +fecally eliminated (can be used in pts w/ renal failure) +diabetes insipidus

prolonged QT, GI discomfort, acute cholestatic hepatitis (avoid in liver disease), eosinophilia, skin rashes; P450 down (increases efficacy of theophylline and oral anticoagulants) anemia (dose dependent), aplastic anemia (dose ind), gray baby sz (in preemies because they lack UDP-glucuronyl transferase) pseudomembranous colitis, fever, diarrhea hypersensitivity, SJS, hemolysis (G6PDD), nephrotoxic (tubulo-interstitial nephritis), teratogen (kernicterus), photosensitive, megaloblastic anemia, P450 down pancytopenia (leuko-, granulocyto-, megaloblastic anemia; may alleviate w/ supplemental folinic acid [leucovorin rescue]) can be used in pregnancy, hemolysis in G6PD deficiency GI upset, superinfxns, tendonitis/rupture (not for pregnant women/kids), headache, dizziness, rash metallic taste, disulfiram-like effect w/ EtOH, headache, mutagenesis neurotoxic, nephrotoxic (acute tubular necrosis) hemolysis (in G6PDD), methemoglobimemia, agranulocytosis orange body fluids, minor hepatotoxicity, ups P450

neurotoxic (seizures), hepatitis, lupus; pyridoxine (B6) can prevent neurotoxicity and lupus; hemolytic in G6PD deficiency, P450 down

fever/chills, hypotension, nephrotoxicity (reduced by hydration), arrhythmias, IV phlebitis, anemia

N/V/D/bone marrow suppression, nonmegaloblastic macrocytic anemia topical (too toxic for oral) liver dysfunction (P450 inhibitor), fever, chills + hypocortisolism (blocks hormone synthesis in adrenals), gynecomastia, amenorrhea + can cross BBB GI upset, flushing teratogen, carcinogen, confusion, headache, increase P450 and warfarin metabolism

hemolytic anemia in G6PD deficiency cinchonism (flushing, sweating, headache, confusion, blurred vision, vertigo, tinnitus, rash, abdominal pain, N/V/D) stimulates depolarization-induced paralysis by stimulating nicotinic receptors at NMJ amplifies GABA-mediated inhibition leading to immobilization; doesn't cross BBB (no effect on humans) increases membrane permeability to Ca (contraction, paralysis) ataxia, dizziness, slurred speech doesn't cross BBB, fewer CNS SFx m

hemolytic anemia, teratogen (severe) no effect on latent virus; resistance=lack of viral thymidine kinase

thrombocyto-/leuko-/neutro-penia, nephrotoxic nephrotoxic, hypo-Ca/PO4/K/Mg; resistance by mutated DNA pol hyperglycemia, N/D, lipodystrophy, P450 inhibition + thrombocytopenia bone marrow suppression (can be reversed with GCSF and erythropoietin), peripheral neuropathy, lactic acidosis + pancreatitis + megaloblastic anemia bone marrow suppression (can be reversed with GCSF and erythropoietin), peripheral neuropathy, rash (SJS)

hypersensitivity, increased risk of bacterial pneumonia

neutropenia

neutropenia neutropenia Immune SFx/Other nephrotoxic (prevented by mannitol diuretic), higher risk for viral infxn and lymphoma significant: hyperglycemia, htn, nephrotoxicity, peripheral neuropathy, pleural effusion hyperlipidemia, thrombocytopenia, leukopenia

bone marrow suppression, worsened w/ allopurinol (6-MP broken down by xanthine oxidase), nonmegaloblastic macrocytic anemia cytokine release syndrome, hypersensitivity rxn

Pharm/Cardio SFx/Other

exacerbation of COPD/asthma (M3), and peptic ulcers (M1 and M3); severe/OD on AChEI: DUMBBELS=diarrhea, urination, miosis, bradycardia, bronchospasm, excitation of CNS and skeletal mm, lacrimation, sweating, salivation constipated, urine retention, mydriasis, cyclopegia, acute angle closure glaucoma, bronchodilation, tachycardia, disorientation, increased T, and dry eyes, skin, and mouth (hot, dry, red, blind, mad, all analogies) tx OD w/ physostigmine salicylate

severe orthostatic hypotension, blurred vision, constipation, sexual dysfunction

DON’T use in closed angle: causes mydriasis and can block angle more

pupillary dilation, vasoconstriction, nasal decongestion tachyphylaxis (rebound congestion/continence[?]) fetal abnormalities, fetal addiction, placental abruption, coronary vasospasm; OD: pupil dilation, hallucinations (esp tactile), paranoia, angina, tx=BDZ; withdrawal: suicidal, hypersomnolent, malaise

direct Coombs-positive hemolytic anemia ergotism orthostatic hypotension, reflex tachycardia

1st dose orthostatic hypotension, dizziness, headache impotence, exacerbation of asthma, CV effects (bradycardia, AV block, CHF), CNS effects (sedation, sleep alteration), caution in DM (tx OD w/ glucagon), partial agonists (pindolol and acebutolol) contraindicated in angina; metoprolol can cause dyslipidemia

mnemonics class II antiarrhythmics: help with Most suPrAvEnTriculars= metoprolol, propranolol, atenolol, esmolol, timolol; Partial agonists: pindolol, acebutolol; selective β1: A-M (atenolol, acebutolol, betaxolol, esmolol, metoprolol); nonselective: N-Z (nadolol, pindolol, propranolol, timolol)

reflex tachycardia (contraindicated in angina/CAD, commonly given w/ β- blocker), Lupus-like sz cutaneous flushing, cardiac depression, AV block (careful in WPW), peripheral edema, dizziness, constipation, gingival hyperplasia

+ peripheral edema, reflex tachycardia

reflex tachycardia, hypotension, flushing, dizziness, headache (esp in industrial exposure: "Monday Dz", tolerance common) cyanide toxicity hyperglycemia (reduces insulin release) hepatotoxicity, rhabdomyolysis cutaneous flushing (esp face), hyperglycemia, acanthosis nigricans, hyperuricemia pts hate it: tastes bad, constipation, decreased abs of fat soluble vitamins, chlsl gallstones rare increase in LFT myositis, hepatotoxicity (LFT), chlsl gallstones gynecomastia, cholinergic (N/V/D), blurry yellow vision, ECG (high PR, low QT, scooping, inverted-T, arrhythmia), hyperK; OD worse w hypoK, renal failure, and quinidine (decreased clearance); tx OD w/ digoxin immune Fab, slowly normalize K, lidocaine, cardiac pacer, Mg toxicity increased w/ hyperkalemia

Torsades, cinchonism (tinnitus, headache), thrombocytopenia Lupus-like sz CNS stimulation/depression, CV depression

proarrhythmic, esp post MI (contraindication)

Torsades, excessive β-block torsades new arrhythmias, hypotension (emergency use only)

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) cutaneous flushing, hypotension, chest pain (blocked by theophylline)

Endocrine SFX/other

skin rash, aplastic anemia, agranulocytosis (rare) + hepatotoxicity nausea, cramps, steatorrhea

given intranasal for DI hypoglycemia, hypersensitivity (very rare)

disulfiram-like effect w/ EtOH, hypoglycemia

hypoglycemia

lactic acidosis (contraindicated in renal failure) weight gain, edema, hepatotoxicity, CV toxicity

diarrhea

hypoglycemia, N/D N/V, pancreatitis tachycardia, heat intolerance, tremors, arrhythmias

stimulates labor, uterine contractions, milk let-down, controls uterine hemorrhage iatrogenic Cushing's (incl. osteoporosis [contraindication], peptic ulcers, and DM), adrenal insufficiency when drug stopped after chronic use

GI SFX/other tx OD w/ physostigmine salicylate; tachycardia, dry mouth, difficulty focusing eyes

none (most H2 blockers); cimetidine: P450 down, gynecomastia (antiandrogenic, PRL release, impotence, decreased libido), can cross BBB (confusion, dizziness, headaches); ranitidine and cimetidine: decrease renal excretion of creatinine

black tongue, stool

diarrhea, abortifacient

constipation, hypophosphatemia, mm weakness, osteodystrophy, seizure diarrhea, hyporeflexia, hypotn, cardiac arrest hyperCa, rebound acid level, chelates other drugs malaise, nausea, sulfa, reversible oligospermia

respiratory infxn (reactivation of latent TB bc TNF-α maintains granulomas), fever, hypotension headache, constipation Parkinsonian, restlessness, drowsiness, depression, N/D; interacts w/ digoxin and diabetic agents; contraindicated in SI obstruction Heme/Onc SFX/other teratogen (spontaneous abortion, cleft palate, cardiac abnormalities); when txing PML, can release Auer rods and cause DIC follow PTT; bleeding, thrombocytopenia/clotting (HITT, binds PF4 [platelet factor 4, natural CXCR4L]), osteoporosis; antidote= protamine sulfate (positive, binds) not easily reversible, similar sfx

monitor PT, metabolized by P450; antidote=vitamin K; for more rapid reversal, give FFP; skin/tissue necrosis; teratogen (bone deformities, fetal hemorrhage, abortion) bleeding, treat toxicity with aminocaproic acid or tranexamic acid (plasminogen activation inhibitors)

neutropenia bleeding, thrombocytopenia

myelosuppression (leucovorin rescue), macrovescicular fatty liver, mucositis (aphthous ulcer), teratogenic; tx OD by alkalinizing urine myelosuppression (non-megaloblastic microcytic anemia, thymidine rescue), photosensitivity nonmegaloblastic macrocytic, GI, liver; increased toxicity w/ allopurinol marrow depression, can be given w/ allopurinol leukopenia, thrombocytopenia, megaloblastic anemia myelosuppression cardiotoxicity (dilated CM, protected by dexrazoxane [Fe-chelation]), myelosuppression, alopecia; toxic to tissues with extravasation pulmonary fibrosis, skin changes, minimal myelosuppression myelosuppression, GI irritation, alopecia CNS toxicity; all alkylating agents: teratogen (missing digits), aplastic anemia myelosuppression, hemorrhagic cystitis (lessened by mesna, better control w/ ifosfamide); SIADH for cyclophosphamide disulfiram-like effect w/ EtOH pulmonary fibrosis, hyperpigmentation neurotoxic (areflexia, peripheral neuritis), paralytic ileus bone marrow suppression myelosuppression, hypersensitivity nephrotoxic, ototoxic

nonmegaloblastic macrocytic anemia, GI upset cardiotoxic

fluid retention

Musculoskeletal SFX/other all NSAIDs: inhibit dilation of afferent arteriole, drop GFR (acute renal failure), intersitial nephritis, gastric upset/ulceration/bleed, and aplastic anemia; hemolytic anemia in G6PDD, CN VIII issues, mixed RAlk (hyperpnea) and MAc; Reye's syndrome in kids (esp w/ viral infxn) all NSAIDs: inhibit dilation of afferent arteriole, drop GFR (acute renal failure), intersitial nephritis, gastric upset/ulceration/bleed, and aplastic anemia; fluid retention; ibuprofen: hemolytic anemia in G6PDD

higher risk of thrombosis, sulfa allergy, lower incidence of GI sfx no Reye's sz, but OD causes hepatic necrosis (metabolyte depletes glutathione and forms toxins in liver), N-acetylcysteine is antidote; chronic use can cause renal papillary necrosis corrosive esophagitis, N/D, osteonecrosis of jaw no corrosive esophagitis (IV) GI side effects, agranulocytosis

sulfa allergy

SJS, increases concentrations of azathioprine and 6-MP (both metabolyzed by xanthine oxidase, give 6-tG instead of 6-MP) Neuro SFX/other

darkens iris

exacerbation of COPD, asthma, and peptic ulcers; severe/OD on AChEI: DUMBBELS=diarrhea, urination, miosis, bradycardia, bronchospasm, excitation of CNS and skeletal mm, lacrimation, sweating, salivation

Respiratory depression, miosis (pinpoint pupils), additive CNS depression with other drugs (EtOH, BDZ, barbiturates, 1B antiarrhythmics), addiction, constipation, N/V; tolerance does not develop to miosis and constipation; do not use morphine in renal failure, acute respiratory depression, high ICP (can worsen respiratory depression), biliary colic -OD (life- threatening) txed w/ naloxone or naltrexone (opioid ant) threatening) txed w/ naloxone or naltrexone (opioid ant)

-withdrawal: flu-like (sweating, dilated pupils, piloerection ["cold turkey"], fever, rhinorrhea, N/D/stomach cramps); symptomatic tx -heroin: high risk for hepatitis, abscess, OD, hemorrhoids, AIDS, RHF similar to opioids, decreases seizure threshold less respiratory depression, causes withdrawal if on full ag

Lupus-like sz, SJS, peripheral neuropathy, megaloblastic anemia (low folate absorption), nystagmus, diplopia, ataxia, sedation, teratogen (fetal hydantoin sz=IUGR), gingival hyperplasia, hirsutism, P450 up diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenic, P-450 induction, SIADH, SJS SJS sedation, ataxia sedation, mental dulling, kidney stones, weight loss sedation, tolerance, dependence, P-450 induction (contraindicated in porphyria), CNS depression (additive w/ EtOH), SJS; OD: respiratory/ cardiac - depression (can cause death), supporative tx and HCO3 (alkalinize urine); withdrawal: delerium, CV collapse (life-threatening) GI distress, hepatotoxicity/necrosis (can be fatal, measure LFTs), teratogen (neural tube defects), tremor, weight gain fatigue, GI distress, headache, urticaria, SJS

much larger safety margin than barbiturates, and less respiratory depression; usually long t1/2 and active metabolites (short acting BDZs have higher addictive potential); sedation, tolerance, dependence, CNS depression (additive w/ EtOH); OD: ataxia, minor respiratory depression; tx=flumazenil (competitive antagonist at GABA-R)

short t1/2 (rapidly degraded in liver), so less day-after SFX; ataxia, headaches, confusion; lower dependence risk than BDZ hepatotoxicity/necrosis, malignant hyperthermia (all but N2O) proconvulsant nephrotoxicity CV stimulant, disorientation, hallucinations, bad dreams, increase cerebral BF

less post-op nausea than thiopental can cause hyperCa, hyperK, malignant hyperthermia

reversal: AChEI (neostigmine, edrophonium)

can cause ataxia arrhythmias from peripheral conversion to DA; long term can cause dyskinesia following dose, akinesia between doses

Parkinson-like sz

dizziness, confusion, hallucinations N/V, dizziness, insomnia

coronary vasospasm (don't use in pts with CAD or Prinzmetals angina), mild tingling Psych SFX/other atropine-like: dry, constipation, hypotn, sedation; corneal (chlorprom-) or retinal (thiorid-) deposits; both: neuroleptic malignant sz: autonomic instability, myoglobinuria, rigidity, hyperpyrexia, encephalopathy extrapyramidal (4h=dystonia [mm spasm]; 4d=akinesia [parkinsonian]; 4wk=akathisia [restlessness]; 4mo=tardive dyskinesia [irreversible stereotypic oral-facial movements from long-term use]), hyperPRL far fewer extrapyramidal and anticholinergic SFx than neuroleptics

wt gain, agranulocytosis (requires weekly WBC monitor) wt gain teratogen (atrialized RV [Ebstein's anomaly, malformation of great vessels]), hypothyroid, nephrogenic DI, sedation, edema, heart block, tremor; narrow therapeutic window no sedation, addiction, tolerance, EtOH interaction (BDZ/barbiturates) sedation (least=desipramine), convulsions (most=desipramine), α-blocking and anticholinergic (tachycardia, arrhythmias, urinary retention, confusion,

hallucinations; 3°>>>2°), hyperpyrexia; tx OD w/ NaHCO3 (alkalinize urine)

less than TCAs: GI distress, sexual dysfunction, "Seratonin sz" (drug interactions, too much 5-HT causes HyperThermia, HyperTonism, CV collapse,

flushing, diarrhea, seizures; tx=cyprohepadine [5HT2 ant]) stimulant effects (htn most common), sedation, nausea

htnsive crisis (w/ tyramine ingestion and β-ag), CNS stimulation, contraindicated w/ SSRIs or meperidine (prevent seratonin sz)

+ may enhance SFX from levodopa abnormal dreams, change in taste, flatulence/constipation, suicide stimulant effects (tachycardia, insomnia), headache, seizure in bulimia sedation, increased appetite, dry mouth, increased serum cholesterol sedation, orthostatic hypotension sedation, nausea, priapism, postural hypotension OD: pupil dilation, prolonged wakefulness, delusions, hallucinations, fever; withdrawal: stomach cramps, hunger, hypersomnolent

Addiction Intoxication mood elevation, decreased anxiety, sedation, behavioral disinhibition, respiratory depression emotional lability, ataxia, coma, serum GGT (sensitive EtOH use), AST>2*ALT; acute EtOH=P450 down; chronic EtOH=P450 up, ; assn w/ periventricular hemorrhage/necrosis of mammillary bodies mood elevation, psychomotor agitation, insomnia, arrhythmias, tachycardia, anxiety restlessness, diuresis, muscle twitching teratogen (preterm labor, placental problems, IUGR, ADHD) homocidality, delerium, belligerence, fever, nystagmus, tachycardia, psychomotor agitation, impulsiveness

, pupillary dilation, marked anxiety/depression, delusions, visual hallucinations paranoid delusions, slowed time perception, social withdrawal, dry mouth, hallucinations

Renal SFX/other pulmonary edema, dehydration, contraindicated in anuria and CHF hyperchloremic (nAG) MAc, neuropathy, NH3 toxicity, sulfa ototoxicity, hypokalemia, dehydration, interstitial nephritis + sulfa allergy and gout hypokalemic MAlk, hyponatremia (low big 3), hyperglycemia, hyperlipidemia, hyperuricemia (gout), hypercalcemia, sulfa allergy hyperkalemia, MAc endocrine SFx (antiandrogen, gynecomastia, amenorrhea) hyperkalemia, MAc cough (not ARBs), angioedema (lip/larynx edema), teratogen (renal damage), proteinuria, taste change, hypotn, hyperK; NOT in bilateral renal a stenosis (decrease GFR by preventing efferent constriction) Repro SFX/other antiandrogen, N/V masculinization in females, reduces intratesticular testosterone in males (inhibits LH) causing gonadal atrophy, premature closure of epiphyseal plates, raise LDL, lower HDL gynecomastia

endometrial cancer, postmenopausal bleeding, VTE; contraindications: ER- positive breast cancer, hx of DVTs teratogen (vaginal clear cell adenoC) hot flashes, ovarian enlargement, multiple pregnancies, visual disturbances endometrial carcinoma, hot flashes

unopposed estrogen RT increases the risk of endometrial cancer (P added), possible increased CV risk masculinization, premature epiphysial plate closure

heavy bleeding, N/V, anorexia, abdominal pain

headache, flushing, dyspepsia, impaired blue-green color vision, life- threatening hypotn in pts taking nitrates Respiratory SFX/other sedation, antimuscarinic, anti-α-adrenergic

less entry to CNS than 1G, so far less sedation

anti-DUMBBELSS

tachycardia

tremor, arrhythmia narrow TI (OD=β-blocker), cardio-/neuro-toxic, metabolized by P450 does not suppress cough reflex

Biochem Excess acute: N/V/dizziness, blurred vision; chronic: hepatotoxicity, increased ICP, papilledema, arthralgias, fatigue, headaches, skin changes, sore throat, alopecia; teratogenic (cardiac abnormalities, cleft palate) hypercalcemia (delerium, stupor, stones), loss of appetite; seen in sarcoid: activated macrophages pump out vit D

cheilosis (inflammation of lips), corneal vascularization facial flushing (tx of hyperlipidemia), acanthosis nigricans, hyperuricemia

Toxins/Antidotes Mechanism

peroxidation of membrane lipids

inhibits lipoic acid (pyruvate and α-KG DH complexes) electron transport inhibitor electron transport inhibitor inhibit alcohol dehydrogenase

inhibits Na/K ATPase (bind K site) α-amantin inhibits RNA Pol II electron transport inhibitor electron transport inhibitor mitochondrial ATPase inhibitor uncoupling agent 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)=skin, vessels, uterus, fetal tissue, granulation tissue (think Ehlers-Danlos); IV=BM Kwashiorkor: protein malnutrition (lesions, belly); marasmus: energy malnutrition (wasting) essential fructosuria: AR fructokinase def, fructose doesn't enter cells, asxatic except for fructosuria fructose intolerance: AR aldolase B deficiency, F1P accumulation, depletion of P, inhibition of glycogenolysis, gluconeogenesis; sx: hypoglycemia, jaundice, cirrhosis, V; tx: no fructose/sucrose intake 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 alkaptonuria (ochronosis): AR homogentisic acid oxidase def, degrades Tyr to fumarate; sx: mostly benign, urine turns black on standing, dark connective tissue/sclera, older get arthralgias (HGA toxic to cartilige) MSUD: α-ketoacid DH def, no degradation of branched AAs (Ile, Val, Leu); organic acidemia, sweet odor 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 positive-AA transporter (cysteine, ornithine, lysine, arginine); sx: cystine kidney stones (staghorn); tx: acetazolamide (alkalinize urine) fraGile X: 2nd most common cause of M retardation; (CGG) repeat, methylation and underexpression of FMR1, macroochidism, long face, large jaw, big ears, MVP; karyotype in folate def medium=discontinuous staining ionizing radiation causes dsDNA breaks, end-joining enzyme repair (no sequence homology necessary) deamination causes abnormal bases, glycosylation makes AP site, AP endonuclease, DNA Pol, and ligase fix UV makes T-T, UV-specific endonucleases cause site specific strand break, exonuclease removal, Pol/ligase fix (def=XP); DNA Pol III has 3'-5' exonuclease proofreading activity for mismatch repair (def=HNPCC) biotin for carboxylation rxns (pyruvate to OAA, [AAs to] propionyl CoA to succinyl CoA); def=organic aciduria αKG/P/αKADH cofactors: B1, 2, 3, 5, lipoate (LA inhibited by arsenic [vomiting, rice water stool, garlic breath]) PDH def: lactic MAc, neuro sx, hemolytic anemia; can be congenital or acquired (B1 def); tx=fatty/lys/leu diet CF: AR CFTR (7) mutation (commonly Phe 508, abnormal folding, degradation), normally secretes Cl in lungs and GI, resorbs in sweat glands (high Cl in sweat=dxtic); infertility in M (bilateral agenesis of vas), mucus plugs in liver, panc, & lungs (Pseudomonas/S. aureus, chronic bronchitis, bronchiectasis, panc insufficiency, ADEK malabs, FTT, steatorrhea, meconium in newborns); tx=N-acetylcysteine (breaks glycoprotein S-S bonds) OTC def: XLR, most common urea cycle disorder (others AR), usually early onset (can be late), xs carbamoyl-P to orotate; sx: orotic aciduria, low BUN, hyperNH3 (cerebral edema, blurry vision, tremor, V, speech slurring) carnitine def: inability to transport LCFAs into mitochondria; sx: hypoketotic hypoglycemia, hypotonia, weak acyl-CoA DH def: hypoketotic hypoglycemia with dicarboxylic acid-emia/-uria (substrate of deficient enzyme)

Embryo embryonic craniocaudal segmentation caused by homeobox gene, AP-patterning from sonic hedgehog (from ZPA) and Wnt-7 (from AER), limb lengthening induced by FGF (from AER, stimulates mesoderm mitosis) notochord induces overlying ectoderm to neural plate; neural plate becomes neural tube and neural crest cells; notochord becomes nucleus pulposis of intervertebral disks; cardinal vv become SVC allantois: contains umbilical aa & vv, urachus (bladder-yolk sac), vitelline duct (midgut-yolk sac, "yolk stalk") erythropoiesis wk3-8=yolk sac (Gower Hb=ζ2ε2); wk6-30=liver and spleen (9-28, HbF); wk28+=bone marrow indomethacin helps close PDA, PGs (decrease with increase in O2) keep PDA open (PDA=continuous murmur) neural tube defect: high AFP; anencephaly: high AFP, polyhydramnios (no swallowing center) 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) failure of fusion cleft lip=maxillary, medial nasal; palate=lateral palatines, medial palatine, nasal septum wk6: midgut herniates through umbilical ring, returns and rotates around SMA wk10; gastroschisis=extrusion of GI contents through folds, not covered by peritoneum; omphalocele=into umbilical cord, peritoneal cover wk6: midgut herniates through umbilical ring, returns and rotates around SMA wk10; gastroschisis=extrusion of GI contents through folds, not covered by peritoneum; omphalocele=into umbilical cord, peritoneal cover pancreas: dorsal and ventral buds contribute to head, main duct; rest is only dorsal; fusion at wk8 metanephros appears wk5, ureteric bud from caudal end of mesonephros forms ureter, pelvices, calyces, collecting ducts, and induces metanephric mesenchyme differentiation (glomeruli to DCT); ureteropelvic jctn=last site to canalize, most common site of obstruction causing fetal hydronephrosis internal genitalia F=paramesonephric (Mullerian) duct, will fuse; M=mesonephric (Wolffian) duct; external: tubercle=penis or 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) 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) GPR: "BaCCiLuM"=Bacillus, Corynebacterium, Clostridium, Listeria, Mycobacteria (mycolic acid in cell wall) intracellular obligate=Rickettsia, Chlamydia; facultative=Legionella, Neisseria, Mycobacteria (bird), Brucella (cow), Listeria (cow), Francisella (rabbit), Yersinia (prairie dog), Salmonella (reptiles) capsule (polysaccharide): S. pneumo, H. flu, N. meningitides, K. pneumo, Salmonella, B. anthracis (D-glu) virulence factors Protein A (S. aureus, binds Ig Fc), IgA protease (S. pneumo, H. flu, N. meningitides), M protein (S. pyogenes, prevents phagocytosis); E. coli: fimbriae (pyelo/cystitis), H=flagella, K=capsule (meningitis, pneu-monia), O=LPS; paramyxovirus: F-protein (causes respiratory epithelial cells to fuse to multinucleated cells) exotoxins ADP-ribosylating: B=binding, A=active (enzymatic); C. diphtheriae/Pseudomonas exotoxin: inactivates EF-2; V. cholerae (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. botulinum (inhibits ACh release), S. pyogenes (streptolysin O, erythrogenic), Shigella/E. coli O157:H7 (cleaves 60S rRNA) [bold coded on phages] endotoxin macrophages [IL-1 (fever), TNF (fever, hemorrhagic tissue necrosis), NO (hypotn)]; XII (coagulation cascade and DIC); alternate complement pathway [C3 (hypotn, edema), C5 (chemotaxis), both anaphylactic] S. pyogenes: rheumatic fever=subQ nodules, migratory polyarthritis, erythema marginatum, chorea, carditis VDRL: Ab to beef cardiolipin, false positives=viral (EBV, hepatitis), drugs, rheumatic fever, lupus, leprosy Weil-Felix rxn: anti-Rickettsia Abs (not Q-fever) agglutinate w/ Proteus O Ags; monospot=sheep RBCs 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 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 chronic granulomatous dz, acute-branching septate hyphae; C. neoformans: heavy capsule, yeast, narrow- based buds; Mucor/Rhizopus: irregular, non-septate hyphae, frontal lobe in DM Plasmodia schizont to hepatocyte to merozoite to RBC to trophozoite, gametocyte to mosquito; headache, anemia, splenomegaly; malariae: 72hr cyclic fever; vivax/ovale: 48hr cycle, dormant hypnozoite in liver (tx=primaquine); falciparum: daily fever, RBC occlude capillaries (brain, kidney, lung); Babesia: maltese cross vax live (no booster)=VZV, Sabins polio, MMR, smallpox, yellow fever; killed (only humoral immunity)=Salks polio, Rabies, flu, HAV; recombinant=HPV, HBV; H. flu=conjugated capsular polysaccharide/diphtheria toxoid non-infxous genomes dsRNA (reo-) and (-) ssRNA (Always Bring Polymerase Or Fail Replication: Arena, Bunya, Paramyxo, Orthomyxo, Flavi, Rhabdo); segmented: Arena (2), Bunya (3), Orthomyxo (8), Reo (10) exceptions RNA: nuclear replication=orthomyxo and retro, non-encapsulated=enterovirus: calici (norwalk), reo (rota), hepe (HEV), picorna (HAV); DNA: encapsulated=hepadna (think of HCV/HDV, circular), herpes, pox HepB HBe is in the core, indicates viral replication, high transmissibility; anti-HBe=low transmissibility; test: incubation pd (infxn-mo2)=HBs; prodrome/acute (mo2-5)=HBs or anti-HBc; convalescent: early (equivalence/ window period, mo5- 6.5)=anti-HBc, 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 osteomyelitis: usually in children, bone pain and elevated APRs (CRP, ESR), S. aureus usually; can be N. gonorrhea (usually from septic arthritis), P. aeruginosa (DM/IVDU), Salmonella (sickle cell), Pasteurella (bite) - UTI: dysuria, frequency, urgency, suprapubic pain, WBCs, no casts; leukocyte esterase=bacterial, NO2 =GN; E. coli, S. saprophyticus, K. pneumo; nosocomial: Serratia, Enterobacter, Pseudomonas; Proteus=struvite stones 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 rash; HIV: recurrent infxn/diarrhea; HSV: temporal enceph-alitis; Syphilis: hydrops, facial abnormalities (saber shins, Hutchinson's teeth, saddle nose), CN VIII deafness superficial vascular proliferation in HIV lymphocytes=Kaposi's, PMNs=bacillary angiomatosis, from Bartonella

Bug (special medium): B. pertussis (Bordet-Gengou agar), M. TB (Lowenstein-Jensen agar), H. flu (chocolate agar, V [NAD] and X [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. neoformans (mucicaramine or India ink), Legionella/fungi (silver), acid fast (Ziehl-Neelsen), Borrelia/chlamydia/Plasmodium/trypanosomes (Giemsa) bacterioSTaTEC: SMX, Trimethoprim, Tetracyclines, Erythromycin, Clindamycin, Chloramphenicol 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 LNs paracortex: high-endothelial venules; cortex: BC; medulla: cords (lymphocytes, plasma cells), sinuses (macrophages); Spleen red pulp: RBC; marginal zone: APCs; white pulp: follicles (BCs) and PALS (TCs); lymph drainage: above pectinate line to internal iliacs, below pectinate line/superficial thigh/scrotum to superficial inguinals, testes to superficial and deep plexuses to paraaortic TC maturation precursor from bone marrow to thymus; CD4+CD8+TC in cortex, (positive selection), CMJ, into pale medulla (negative 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) Th1: induced by IL-12, regulates cell-mediated response, secretes IL-2, -3, and IFN-γ, inhibited by IL-10 Th2: induced by IL-4, regulates humoral response, secretes IL-3, -4, -5, -6, -10, inhibited by IFN-γ BC: 1=IL from Th2, 2=CD40L; IL-4=IgG (crosses placenta) and IgE; IL-5=IgA (breast milk, mono-/di-mer); -6 & -10 complement C1-4=viral neutralization, C3b=opsonize, C3a or C5a=anaphylaxis, C5a=chemotaxis; deficiencies: autoimmune protectors=C1 esterase (hereditary angioedema) and decay accelerating factor/GPI (PNH); C3=severe recurrent pyogenic sinus/RTI, increased type III hypersensitivity; C5-8=Neisseria bacteremia cell surface proteins TC: TCR, CD3 (signal transduction, OKT-3 blocks), CD28 (signal 2), CD40L (only Th2), CXCR4 (HIV); BC: CD19 (on all BC lymphomas), CD20 (rituximab), CD21 (EBV), CD40 (signal 2), B7; macrophages: B7, CD40, CD14 (endotoxin-R), FcR, C3bR, CCR5 (HIV, mutation=immunity); NK: CD56 (marker), CD16 (IgG Fc) preformed Abs given after exposure to rabies, tetanus, HBV, botulinum toxin Bruton's agammaglobulinemia: BTK defect (tyrosine kinase) blocks pre-BC to immature BC, normal pro-B Hyper-IgM: defective CD40L on Th2, inability to class switch, causes severe pyogenic infxns early selective Ig def: IgA most common, sinus/lung infxn, milk allergy, anaphylaxis w/ transfusion common variable ID: BC maturation def, acquired in 20s, assn w/ autoimmune dzs, lymphoma, low Ig/plasmas 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 primary teeth, hyper-IgE, derm problems (eczema, eg) SCID: can be IL-2R def (most common, XL), adenosine deaminase def, MHC2 mutations; tx=marrow transplant ataxia-telangiectasia: DNA repair (ds breaks) def causes cerebellar defects, IgA def, and spider angiomas Wiskott-Aldrich: XLR, deletion of B and TC; thrombocytopenic purpura, infxns, eczema; high IgE, IgA, low IgM leukocyte adhesion def: defect in LFA-1 integrin (CD18) on phagocytes (binds ICAM-1 on endothelium and APCs); recurrent bacterial infxns, no pus formation, delayed separation of the umbilicus, neutrophilia chronic granulomatous dz: NADPH oxidase def causes absent respiratory burst in PMNs, high susceptibility to catalase positive organisms (S. aureus, E. coli, Aspergillus), negative nitroblue tetrazolium dye reduction test

Path apoptosis intrinsic: up Bax, down Bcl-2 cause increased mitochondrial permeability, cytochrome c release; extrinsic: Fas (CD95)-FasL or perforin/granzyme (+granulysin in CTC) attack; both cause Ca influx, activating caspases, nuclear basophilia/shrinkage (pyknosis), fragmentation (karyorrhexis), fading (karyolysis), blebs granulation tissue: vascular, replaces fibrin in wound; granuloma: wall of macrophages, maintained by TNF-α diapedesis rolling: E-/P-selectins (vessel) bind Sialyl-LewisX (Leukocyte); tight binding: ICAM-1 (v) binds LFA-1 (aka integrin, L); diapedesis: PECAM-1 (CD31, both); migration: bacterial products, C5a, IL-8, LTB4, Kallekrein free radical injury: common in prematurity (retinopathy, BPD), drugs (Fe, acetaminophen, CCl4), reperfusion ESR: inflammatory products coat RBC, cause aggregates (fall at higher rate); low=sickle cell, polycythemia, CHF 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 tumor markers AFP: HCC, nonseminomatous germ cell tumors of testis; S-100: melanoma, neural tumor (astro); β-hCG: hydatidaform mole, choriocarcinoma, gestational trophoblastic tumor; CA-125: ovarian, malignant epithelial tumor; tartrate-resistant acid phosphatase (TRAP): Hairy cell leukemia; CA-19-9: pancreatic cancer chemical carcinogens aflatoxin (from Aspergillus): HCC; vinyl chloride: liver angiosarcoma; CCl4: centrilobular necrosis, fatty change; nitrosamines (smoked foods): stomach and esophagus; naphthalene/analine: bladder chemical carcinogens aflatoxin (from Aspergillus): HCC; vinyl chloride: liver angiosarcoma; CCl4: centrilobular necrosis, fatty change; nitrosamines (smoked foods): stomach and esophagus; naphthalene/analine: bladder Psammoma bodies: thyroid papillary adeno, ovarian serous papillary cystadeno, meningioma, mesothelioma mets to brain: lung>RCC>melanoma>breast>GI; liver: colon>stomach>panc>breast>lung; bone: prostate (blastic), breast (blastic and lytic), lung (lytic), thyroid, testis, kidney 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): thymoma, SCLC; gout or urate nephropathy (hyperuricemia due to excess nucleic acid turnover): leukemias and lymphomas; acanthosis nigricans: adenocarcinoma (usually stomach)

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 efficacy: maximal effect a drug can produce; potency: amount of a drug needed for a given effect NACh: ligand-gated Na/K ch, found in all ANS presynaptic ganglia and skeletal mm; MACh: GPCR, M1-5 GPCRs Gs: stimulates adenylyl cyclase, increasing cAMP, which activates PKA; Gi inhibits adenylyl cyclase; Gq activates

PLC which cleaves membrane PIP2 to IP3 (increases intracellular Ca) and DAG, both activate PKC synapses ACh: vesamicol=packaging I, hemicholinum=reuptake I (choline), botulinum=release I; NE: reserpine= packaging I, cocaine/TCA/amphetamine=reuptake I, guanethidine=release I; NE's presynaptic Rs: M2, AII, α2 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 agonists drop BP via β2 and β blockers also drop BP, via α2 and decreased CO]) 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 consumption = [a(O2)-v(O2)] x CO; during exercise, CO increases first from SV, then from HR SV increased by high preload, low afterload, and high contractility (catecholamines [increase SR Ca pump activity], increased [Ca]in/[Ca]out, or digitalis [indirectly inhibit Na/Ca exchanger]; decreased in acidosis) 4 normally, EF>55%; isovolumetric contraction=highest O2 consumption; resistance proportional to viscosity/r JVP: a wave=atrial contraction, c wave=RV contraction, v wave=systolic filling against closed tricuspid valve 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 on inspiration, from aortic stenosis/LBBB S3: normal in children and pregnancy, abnormal in DCM, "slosh-ing-in"; S4: HCM, "a-stiff-wall" murmur enhanced by decreased venous return (Valsalva, standing): MVP (lax chordae, but increased w/ hand grip) and HOCM (decreased filling, more obstruction, but decreased w/ hand grip, and no midsystolic click) aortic stenosis: ejection click, pulsus parvus et tardus, LVP>>BP, later peaking (fastest flow rate) is worse pacemaker AP phase 0=Cav, slow; no plateau; 4=slow diastolic depol as Na conductance increases (If) 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 T)<400ms; QRS<120ms; U-wave: hypoK, hyperCa, hyperT4, bradycardia AFib: irregularly irregular, no discrete P waves, II or IV and warfarin; AFlutter: sawtooth, IA, IC, III (cardiovert) AV blocks 1: long PR, asxatic; 2, type I=Wenckebach: progressive PR lengthening until dropped beat, asxatic; 2, type 2: dropped beats w/o change in PR, may lead to 3; 3=complete: A and V beat independently, tx=pacemaker ANP: high atrial P, dilates renal afferents, constricts efferents (cGMP) causing aldo-independent diuresis aortic arch responds only to high BP; carotid and aortic bodies respond to pO2, pCO2, and pH; central only responds to pCO2 and pH, not pO2 (causes Cushing's triad: high ICP constricts arterioles causing ischemia, causing reflex htn, bradycardia, respiratory depression) cyanotic ToF: pulmonary stenosis (prognostically most important), RVH, overriding aorta, VSD, "boot-shaped heart" on CXR, cyanotic 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 septal agenesis; tricuspid atresia: no AV connection, causes hypoplastic RV, requires ASD and VSD; TAPVR: pulmonary vv drain to RA, requires ASD late cyanosis Eisenmenger; VSD (commonest CHD)>ASD>PDA (uncorrected can cause differential [LE] cyanosis) aortic coarctation infantile: preductal, assn w/ Turner's, weak femoral pulses; adult: postductal, rib notching 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 fibrous plaque and complex atheroma MI complications CHF (most deaths), arrhythmia (common acutely, through first few days), rupture (wall, papillary muscle, day 3-5=maximal), aneurysm formation, fibrinous pericarditis (3-5d post-MI), Dressler's sz dilated/congestive/eccentric CM: from adriamycin, wet Beriberi, Cocksackie myocarditis, cocaine, Chagas' dz, daunorubicin, EtOH; HCM: Freidrich's ataxia; restrictive/obliterative CM: granulomatous, hemochromatosis, endocardial fibroelastosis (<2yo, assn w/ viruses [esp mumps and Cocksackie]), Loffler's Sz (eosinophils) non-Staph endocarditis: infectious (S. bovis=colon cancer, culture negative=HACEK [H. flu, Actinobacillus, Cardiobacterium, Eikenella, Kingella], Pseudomonas or Candida in IVDU) or non (Libman-Sacks [SLE, wart-like, benign], marantic [hypercoagulable, as in Trousseau's]) Kussmaul's sign: increased JVD on inspiration; RHF, constrictive pericarditis, restrictive CM (not tamponade) acute pericarditis: sharp pleuritic pain, better on leaning forward, friction rub; from MI, RF, virus, uremia; chronic constrictive pericarditis: rapid jugular y-descent (spiked down), pericardial knock, pulsus paradoxus 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 RV filling causes septal deviation and reduced LV filling (pericarditis, tamponade); 3. highly negative intrathoracic P decreases transmural P, increasing afterload (asthma, COPD, croup, apnea) RF: Ab to M protein of S. pyogenes; subQ nodules, polyarthritis (migratory), erythema marginatum, carditis, chorea; Anitschkow's cells (activated histiocytes) coalesce to form Aschoff bodies (giant cells w/i granuloma) benign vascular tumors hemangiomas: strawberry (infancy, spontaneously regress), cherry (elderly, does not regress), pyogenic (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 angiomatosis (Bartonella henselae, PMNs) 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) 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 pancreas: more endocrine cells in tail, αs peripherally, βs centrally, δs interspersed; TRH -[+]> TSH and PRL 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 GLUT-2, aerobic respiration (RLS=glucokinase), ATP binds to K channel and closes, causing depolarization and Ca channel opening, causing exocytosis of insulin

DM type 1: assn w HLA-D3/4, anti-glutamate decarboxylase Abs; acute sx: DKA (higher insulin requirement not met causes ketosis; 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 cataracts) 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 converted peripherally to estrone and estradiol) to testosterone (converted by 5α-reductase to DHT or aromatase to estradiol); desmolase activated by ACTH, inhibited by ketoconazole 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 hyperaldo primary=Conn's: aldo-secreting tumor, htn, hypokalemia, MAlk, may be bilateral; secondary: all cause kidney to perceive low V (renal artery stenosis, CHF, CRF, cirrhosis, nephrotic sz), so secretes high renin 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 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 neuroblastoma: kids, can be anywhere along sympathetic chain, elevated HVA in urine, less likely to have htn, n- myc=worse prognosis; pheo: adults, high urine VMA, episodic htn, headache, perspiration, palpitations, tachycardia, pallor, assn w/ NFM, MEN 2A/B, 10%: malignant, bilateral, extra-adrenal, calcify, kids, familial

PTH chief cells of paraT, PTH inhibited by low Mg (diarrhea, rxs [AG, EtOH, diuretics]); renal PO4 resorption down, ups renal Ca resorption (DCT), stimulates osteoblasts (secrete RANK-L [stimulates osteoclasts, ups bone resorption, raising blood Ca and PO4] and M-CSF), stimulates kidney 1α-OHase (inhibited by calcitriol) 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 hyperPTH 1°: usually adenoma, hypercalcemia, stones, hypoPO4, high alk phos, high cAMP in urine, can cause osteitis fibrosa cystica (cystic bone spaces filled w brown fibrous tissue); 2°: decreased gut Ca absorption, high plasma PO4 (usually from chronic kidney failure) causes hyperplasia, sx=hypocalcemia, hyperPO4, high alk phos; 3°: refractory hyperPTH from chronic renal dz, hypercalcemia; 2°/3° can cause renal osteodystrophy hyperPTH 1°: usually adenoma, hypercalcemia, stones, hypoPO4, high alk phos, high cAMP in urine, can cause osteitis fibrosa cystica (cystic bone spaces filled w brown fibrous tissue); 2°: decreased gut Ca absorption, high plasma PO4 (usually from chronic kidney failure) causes hyperplasia, sx=hypocalcemia, hyperPO4, high alk phos; 3°: refractory hyperPTH from chronic renal dz, hypercalcemia; 2°/3° can cause renal osteodystrophy hypoPTH usually from accidental excision, autoimmune, or DiGeorge; hypocalcemia, tetany, Chvostek's sign (tapping facial n causes mm contraction), Trousseau's sign (occlusion of brachial a w/ BP cuff causes carpal spasm); pseudohypoPTH=Albright's hereditary osteodystrophy: AD kidney unresponsiveness to PTH calcitonin: parafollicular (C-) cells of thyroid, decrease bone resorption of Ca, not important physiologically DI no ADH response, USG<1.006, serum>290mOsM; central (from supraoptic nuc): pit tumor, trauma, surgery, or histiocytosis X, responds to desmopressin; nephrogenic: hereditary, 2° to hypercalcemia, demeclocycline, Li, doesn't respond to desmopressin; ADH responds to Osm before V, acts in medullary collecting duct SIADH: excessive water retention, hypoNa, urine Osm>serum Osm, low aldo; can be from ectopic production, head trauma, pulmonary dz, or rxs (carbamazepine, cyclophosphamide); tx=demeclocycline, water restriction pit adenoma usually PRL (amenorrhea, galactorrhea), then GH (insulin resistance, dx=glucose suppression) NET: most common tumor of appendix, secrete 5-HT, high 5-HIAA in urine, 1/3 (met, multiple, present w/ 2nd malignancy); carcinoid sz: recurrent diarrhea, cutaneous flushing, asthmatic wheezing, R-sided valvular dz, especially metastatic NETs from small bowel, not seen if tumor vessels go to liver (5-HT eliminated first pass) Zollinger-Ellison Sz: gastrin-secreting tumor of pancreas or duodenum, acid hypersecretion, thickened rugae, recurrent ulcers, assn w/ MEN 1; VIPoma: panc tumor, copious diarrhea (sphincter relaxation, H2O excretion)

GI fetal umbilical vein becomes ligamentum teres (in falciform), hepatoduodenal lig contains portal triad submucosal plexus=Meissner's; myenteric plexus=Auerbach's (inner circular, outer longitudinal mm fibers) duodenum: Brunner's (submucosal) glands, crypts of Lieberkuhn (continue into ileum); [goblet cells] highest in jejunum; aorta: T12=celiac; L1=SMA, renal aa (L=lower); L2=gonadal aa (L=higher); L3=IMA; L4=bifurcation short gastric aa: from splenic a, supply fundus, poor anastamoses; block of abdominal aorta can use these anastamoses: S epigastric (internal thoracic) to inf epigastric (external iliac), S pancreaticoduodenal (celiac) to inf. PD (SMA), middle colic (SMA) to left colic (IMA), superior rectal (IMA) to middle rectal (internal iliac) femoral lateral to medial to find NAVEL; triangle (made of SAIL) has all, but sheath doesn't contain the nerve 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 external inguinal ring; indirect: M>F, congenital, through deep inguinal ring, failure of processus vaginalis to close, can form hydrocele; femoral: F>M, thru femoral canal saliva parotid (serous), sublingual (mucinous); stimulated by parasympathetic (VII, IX) and superior cervical ganglia (T1- 3); α-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) salivary gland tumors usually in parotid; pleomorphic adenoma: most common, painless, movable, high rate of recurrance; Warthin's tumor: benign, heterotopic salivary tissue in LN; mucoepidermoid carcinoma gastric acid secretion: H/K ATPase, H produced by carbonic anhydrase, bicarb exchanged for Cl basolaterally pancreas α-amylase & lipase secreted in active form, colipase (activated by trypsin) necessary for lipase to be effective; entero- kinase/-peptidase (duodenal excretion) activates trypsinogen, which activates all proteases oligosaccharides: hydrolases at brush border of intestine, RLS in carb digestion, makes monosaccharides; absorption: glucose and galactose by SGLT1 (Na dependent), fructose by GLUT-5; all basolaterally use GLUT-2 Peyer's patches: unencapsulated, specialized M cells take up Ag, BCs differentiate to IgA-secreting; bile: bile salts (acids conjugated to glycine or taurine), phospholipids, chlsl (only method of excretion), bilirubin, water 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 esophageal rupture from violent retching; Plummer-Vinson: webs (dysphagia), glossitis, Fe def anemia; Barrett's: intestinal metaplasia; esophagitis: from bisphosphonates 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 malabsorption abetalipoproteinemia; pancreatic insufficiency: CF, obstruction, chronic panc; disaccharidase def: osmotic diarrhea, 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 hyperplasia, and lymphocyte infiltrate (lamina propria) in proximal bowel, associated with dermatitis herpetiformis and increased risk of TC lymphoma gastritis acute/erosive: NSAIDs (RA), EtOH, uremia, burns (Curling's), brain injury (Cushing's); chronic: type A (body/fundus: Abs to parietal cells) and type B (antrum: most common, H. pylori infxn, increased risk of MALT) PUD clean margins; gastric: decreased mucosal protection, greater pain w/ meals, H. pylori in 70%; duodenal: increased gastric secretion and decreased mucosal protection, pain decreased with meals, H. pylori in 100% 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 gastritis; signet ring cells, acanthosis nigricans; linitis plastica=diffuse 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) 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 intussusception: usually kids (adenovirus), in adults=intraluminal tumor; volvulus: usually elderly Hirschsprung dz: failure of neural crest cells to migrate, causes congenital megacolon, always involves rectum angiodysplasia: tortuous dilation of vessels, bleed; usually ileum/R-sided, older pts 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 involves rectum; Gardner's, Turcot's), HNPCC (aka Lynch Sz, AD DNA mismatch repair defect, always involves proximal colon); distal=obstruction, hematochezia; proximal=dull pain, anemia CRC: higher risk with IBD, S. bovis sepsis, use CEA tumor marker; 1. microsatellite instability (by mismatch repair gene mutations); 2. APC mutation (decreased cellular adhesion, increased prolif via β-catenin), KRAS mutation (unregulated intercellular signal transduction) causes adenoma, loss of p53 marks carcinoma micronodular cirrhosis: <3mm nodules, from metabolic insult (EtOH, macrolides); macronodular: >3mm nodules, significant liver injury causing hepatic necrosis (infxn, halothane, acetaminophen, valproate), HCC EtOH hepatic steatosis: moderate intake causes short term, macrovescicular change, reversible; hepatitis: long-term EtOH, swollen/necrotic hepatocytes, PMN infiltrates, Mallory bodies (intracytoplasmic eosinophilic inclusions, "twisted- rope"); cirrhosis: micronodular "hobnail", sclerosis around central vein (zone III) HCC: jaundice, tender HSM, ascites, hypoglycemia, polycythemia, Budd-Chiari; spreads hematogenously, AFP α1-AT def: misfolded gene product, decreased elasticity of lungs (panacinar emphysema) and PAS-positive globules in the liver (cirrhosis and liver failure); codominant trait hemochromatosis=dz caused by hemosiderosis (Fe deposition)=micronodular cirrhosis, "bronze diabetes" (DM, skin pigmentation), 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 biliary tract dz sx=pruritis, jaundice, dark urine, light stools, HSM; labs=high direct bilirubin, chlsl, GGTP, alk phos; PSC: idiopathic concentric "onion skinning" fibrosis causes "beads on a string" of any bile ducts, assn w/ hyperIgM, ulcerative colitis; PBC: anti-mitochondrial Abs causes PMN infiltrate, granulomas; SBC: high intraductal pressure from obstruction causes fibrosis and stasis, complication=ascending cholangitis 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 sign), ascending cholangitis (Charcot's triad: jaundice, fever, RUQ pain), pancreatitis, biliary colic (can be painless in DM), fistulas, gallstone ileus (usually ileocecal jctn)

Heme/Onc eosinophils: major basic protein (anti-helminth), histaminase and arylsulfatase (limit reaction after mast cell degranulation); eosinophilia=NAACP: neoplasm, allergy, asthma, collagen vascular dz, parasites (Loffler's) basophil: granules of heparin, histamine, and vasoactive amines (LT); mast cell: + eosinophil chemokines agranulocytosis=granulocytopenia: PTU/methimazole, colchicine, carbamazepine, clozapine, dapsone platelet plug formation vWF binds subendothelial collagen, platelets bind vWF (GpIb), release dense granules (Ca [necessary for coagulation cascade], ADP [helps platelets adhere to endothelium and induces GpIIb/IIIa to platelet surface]), fibrinogen binds GpIIb/IIIa, links platelets; aggregation: pro=TXA2 (platelets), anti=PGI2 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 factor activation but XII, VIII, V, and I; IIa=thrombin, Ia=fibrin; protein S activates protein C, which inactivates Va, VIIIa; tPA + vWF from endothelial cells, vWF protects VIII coagulopathy hemophilia: A=VIII, B=IX; vit K def/warfarin=loss of cofactor for γ-carboxyglutamation rxn, inactive II, VII, IX, X, C, S; Bernard-Soulier: GpIb def; Glanzmann thrombasthenia: def GpIIb/IIIa; ITP: anti-GpIIb/IIIa Abs, increased megakaryocytes; TTP: ADAMTS 13 def (vWF metalloprotease), vWF multimers, clots, schistocytes, pentad=neuro/renal sx, fever, thrombocytopenia, microangiopathic hemolytic anemia; vW dz: mild, AD; factor V Leiden: Va resistant to APC; C/S def: risk of thrombotic skin necrosis/hemorrhage w warfarin

DIC causes: sepsis (GN), trauma, OB complications, acute pancreatitis, malignancy, nephrotic sz, transfusion microcytic hypochromic anemia MCV<80, basophilic stippling of RBCs; Fe deficiency (duodenal abs), anemia of chronic dz, thalassemia (α: 3 mutations=HbH (β4); β: high HbF, minor [asxatic, high HbA2] or major [severe anemia, 2° hemochromatosis, marrow expansion, chipmunk facies]), Pb poisoning, sideroblastic anemia macrocytic anemia MCV>100, macroovalocytic RBCs, impaired DNA synth; megaloblastic: hypersegmented PMNs, glossitis, high homocysteine; folate def: jejunal abs, normal methylmalonate, seen w/ MTX, TMP, hemolytic anemia, pregnancy; B12 def: Schilling test, ileal abs, D. latum, causes neuro sx (subacute combined degeneration of posterior columns, peripheral nerves, lateral 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 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 abnormal RBCs acanthocyte: liver dz (abetalipoproteinemia); target cell: high SA:V ratio (high membrane, low heme=HbC, asplenia, liver dz, thalassemia); Heinz bodies: ferric heme pption, in α-thalassemia, G6PDD 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->uroporphyrinogen III-[uroporphyrinogen decarboxylase (porphyria cutanea tarda)]-> coproporphyrinogen III -> protoporphyrin -[+ Fe, ferrochelatase (Pb poisoning)]-> heme (feeds back onto δ-ALA synthase); porphobilinogen & uroporphyrinogen are converted to uroporphyrin

P. cutanea tarda: most common, tea-colored urine, blistering cutaneous photosensitivity; acute intermittent P.: red-wine colored urine, abd pain, polyneuropathy, psych disturbances, ppted by rxs, tx=glucose and heme

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 surrounding nodules), mixed cellularity (more RSCs), lymphocyte predominant (rare), lymphocyte depleted (very rare, high RS to lymphocyte ratio, older men, poor prognosis) lymphoma diffuse large cell lymphoma: most common NHL, usually in elderly (20% kids), mostly BC (20% TC); BC: Burkitt's: young, 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 multiple myeloma: commonest 1° bone tumor, monoclonal plasma cell (fried egg), IgG>IgA, infxn-prone, lytic bone lesions (hypercalcemia), M-spike, anemia, renal failure (Bence Jones proteins, AL [1° amyloid]), rouleaux Waldenstrom's macroglobulinemia: hyperIgM, hyperviscosity sx; MGUS: monoclonal expansion, no sx 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 AML: Auer rods (fused granules), myeloblasts; AML M3: responds to all-trans vit A (induces differentiation); CML: Philadelphia chromosome=t(9;22), bcr-abl, granulocytosis, metamyelocytes, SM, can have blast crisis (AML or ALL), low alk phos (differentiate from leukemoid rxn), responds to imatinib (TK inhibitor) Langerhans cell histiocytosis: S-100+, CD1a+, Birbeck granules (tennis rackets) on EM; can cause DI chronic myeloproliferative disorders (other than CML) all have JAK2 mutations in stem cell; polycythemia vera: mutation in early cell, 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); macula adherens (desmosome): cadherens bind intermediate filaments; integrins to BM rotator cuff: supraspinatus (abduction before deltoid, most common cuff injury), subscapularis (adduction and medial rotation), infraspinatus and teres minor (adduction and lateral rotation) other nerve lesions Erb's palsy (waiter's tip): upper trunk (C5-6), paralysis of abductors, lateral rotators, and biceps (so pronated); posterior cord; deltoid paralysis + wrist drop; long thoracic n: winged scapula; thoracic outlet sz (cervical rib): Klumpke's palsy and disappearance of radial pulse on moving head ipsilaterally other nerve lesions Erb's palsy (waiter's tip): upper trunk (C5-6), paralysis of abductors, lateral rotators, and biceps (so pronated); posterior cord; deltoid paralysis + wrist drop; long thoracic n: winged scapula; thoracic outlet sz (cervical rib): Klumpke's palsy and disappearance of radial pulse on moving head ipsilaterally skeletal/cardiac mm contraction nAChR causes depol, travels down T-tubule, activates DHPR, lets in Ca, Ca activates ryanodine R on SR, more Ca release, Ca binds troponin C, moves tropomyosin from myosin-binding sites on actin; H-/I- bands shrink, A doesn't; type 1=slow, red; type 2=fast, white (hypertrophy, don't switch) smooth mm contraction membrane depol, Cav (DHP, L-type) open, Ca binds calmodulin, activates myosin light chain kinase (MLCK), P-ation, cross bridge formation; cGMP inhibits MLCK, MCLPhosphorylase inactivates achondroplasia: constitutive FGFR3 inhibits chondrocyte prolif, failure of long bone growth (endochondral ossification, short limbs), membranous ossification fine (big head); AD, but 85% sporadic (hi paternal age) nl bone labs osteoporosis: reduction of spongy bone mass despite normal bone mineralization; I=menopause; II=age; vertebral crush fracture, femoral neck, distal radius (Colle's); corticosteroids, heparin, homocystinuria nl bone labs (cont'd) osteopetrosis: carbonic anhydrase II def, no osteoclast fctn, failure of nl resorption, too dense (prone to breaks), pancytopenia (low marrow space, extramedullary hematopoiesis), CN impingement high alk phos Paget's dz (osteitis deformans): increased osteo-clast, then -blast activity causes "mosaic" bone architecture, possibly viral origin (paramyxo-), chalk-stick fractures, AV shunts (high-output cardiac failure), osteogenic (increased hat size, CN impingement, 2° osteosarcoma/fibrosarcoma); also think 1° hyperPTH osteomalacia/Rickets: defective mineralization, from vitamin D def, usually high PTH, alk phos, low Ca and PO 4 polyostotic fibrous dysplasia: fibroblasts, collagen, and irregular trabeculae replace bone; McCune-Albright 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) RA: synovial joints, MCP/PIP pannus formation, subQ nodules (fibrinoid necrosis surrounded by palisading histiocytes), NO DIP 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 seronegative spondyloarthropathies no RF, assn w/ HLA-B27, M>F; psoriatic arthritis: pencil-in-cup, dactylitis (sausage fingers), minority of psoriatic pts; ankylosing spondylitis: spine and sacroiliac inflammation, bamboo spine, uveitis, aortic regurg; IBD; Reactive arthritis: conjunctivitis/uveitis, urethritis, arthritis Sicca sz: dryness, chronic bronchitis, reflux esophagitis; Sjogren's: dry eyes/mouth, arthritis, anti-RNP (Ro/La) gout: MSU crystalization in joints (negatively birefringent=yellow crystals on parallel), M>F, 90% from under-excretion (diuretics), 10% overproduction (Lesch-Nyhan, PRPP excess, high cell turnover, von Gierke's Dz); sx: asymmetric, swollen, red, painful, big toe MTP (podagra), tophi in external ear, olecranon bursa, Achilles), attacks common after big meal or EtOH binge; acute=NSAIDs, colchicine; chronic=allopurinol, uricosurics pseudogout: CaPP crystals (blue when parallel, rhomboid, weakly positively birefringent), large joint (knee) infectious arthritis septic: S. aureus, Strep, N. gonorrhea common, monoarticular, migratory, can be synovitis or can also affect tendons (tenosynovitis); chronic: TB, Lyme SLE 90% F 14-45, black, die of renal failure and infxn; wire-loop kidney lesions (nephritic), false positive VDRL (from antiphospholipid Ab="Lupus anticoagulant", pro-thrombotic in vivo, causes miscarriages), assn w/ Raynaud's, verrucous endocarditis, hilar LAD; sx: skin (malar, discoid, photosensitivity, mucositis), organ (neuro, renal, serositis, hematologic, arthritis), and lab tests (anti-phospholipid, ANA [sensitive, not specific], anti-Smith [specific, not prognostic], anti-dsDNA [specific, bad prognosis], anti-histone [drug-induced]) sarcoid: immune-mediated non-caseating granulomas, elevated ACE levels, hypergammaglobulinemia, anergy, uveoparotitis, hypercalcemia (macrophage-production of 1α-hydroxylase), Schaumann (giant cell inclusions, seen in granulomas, calcium and 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 ESR), assn w/ giant cell arteritis; polymyositis: CD8 TC injury to myofibers, symmetric progressive proximal mm weakness (shoulders), high CK, aldolase, positive ANA, anti-Jo-1; dermatomyositis: polymyositis + Gottron's papules (extensor surfaces), mechanic's hands, malar/shawl/heliotrope (racoon eyes) rash, high risk of malignancy, dx=mm biopsy w/ evidence of perifascicular inflammation; tx=steroids scleroderma: excess fibrosis and collagen deposition; CREST=anti-centromere, diffuse=anti-topoisomerase I non-infxous derm atopic dermatitis (eczema): pruritic eruption, usually in flexures; ephelis: freckle; psoriasis: acanthosis (spinosum 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/ pregnancy/OCP; pemphigus vulgaris: anti-desmosome, reticular IF, acantholysis, Nikolsky's sign (skin separates on stroking); bullous pemphigoid: linear IF stain, eosinophils, spares oral mucosa; dermatitis herpetiformis: IgA deposits; eryhtema multiforme: drugs (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, sarcoid; keratoses: actinic=premalignant, seborrheic=benign neoplasm; acanthosis nigricans: hyperinsulin, visceral malign'cy, B3; pityriasis rosea: herald patch, pine tree photosensitivity: sulfonamides, amiodarone, tetracyclines, SLE, porphyria cutanea tarda, Weil's Sz 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 UMN lesion: spastic paralysis, clasp-knife spasticity, no atrophy; LMN: fasciculation (twitching), atrophy pain/T: C-fibers=unmyelinated, Aδ=lightly myelinated; large myelinated: Meissner (dynamic fine touch, upper dermis), Pacinian (vib/pressure, lower dermis), Merkel's disk (small, around hair follicles, static touch) spinal cord goes to L1-2, subarachnoid goes to S2, LP usually L3-4/4-5 (level of cauda equina) basal nucleus of Meynert (substantia innominata): ACh-rich, degenerate in Alzheimer's and Huntington's 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 terminalis), area postrema, or neurosecretory areas (pit, eg), all 3 act on hypothalamus hypothalamus supraoptic nuc makes ADH, paraventricular nuc makes oxytocin; lateral area: hunger, inhibited by leptin; ventromedial area: satiety (craniopharyngioma can destroy VMA, cause hyperphagia); anterior: cooling, parasympathetic; posterior: heating, sympathetic; suprachiasmatic nucleus: circadian rhythm thalamus VPL=peripheral sensation, VPM=face sensation/taste, to somatosensory cortex; LGN=eyes, MGN=ears limbic system cingulate gyrus, hippocampus, fornix, mammillary bodies, septal nuc, for the 5 F's cerebellum contralateral cortical input via middle peduncle, ipsilateral proprioceptive via inferior peduncle, input=climbing and mossy 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 coordination, fall ipsilaterally]) basal ganglia DA from SNc to striatum (caudate=cognitive, putamen=motor, ACh-modulation causes tonic inhibition); direct: D1 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 inhibiting thalamus; both cause motion myoclonus=hiccup; dystonia=cramp; chorea (sudden) and athetosis (slow) classic for basal ganglia lesion precentral gyrus=motor, postcentral=sensory; medial-lateral: foot, leg, arm, hand, face (top to bottom), mouth brain lesions reticular activating system (midbrain): reduced arousal and wakefulness (coma); STN: contra-lateral hemiballismus; 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 rapid correction of hyponatremia causes central pontine myelinolysis: acute paralysis, dysarthria, dysphagia, diplopia, loss of consciousness, axial T1 image shows increased signal in the pons posterior cricoarytenoids: open cords; recurrent laryngeal n injury loses all mm except cricothyroid (vagus) vertebral/anterior spinal a (medial medullary sz): pyramid (contralateral LE hemiparesis), medial lemniscus (lower contralateral proprioception), hypoglossal fibers (ipsilateral tongue paresis) PICA (lateral medullary sz): lateral spinothalamic tract (contralateral pain/T), nucleus ambiguus (efferent X, ipsilateral dysphagia, hoarseness, no gag reflex), VIII (vertigo, diplopia, nystagmus, N/V), descending sympathetics (ipsilateral Horner's), V nucleus and tract (ipsilateral facial sensation), ICP (ipsilateral ataxia) AICA (lateral pontine sz): V and VII (ipsilateral face), VIII (nystagmus), ICP and MCP (ipsilateral dystaxia) posterior cerebral a: contralateral hemianopia w/ macular sparing (supplies occipital cortex) middle cerebral a: contralateral paralysis (lower half of face down, upper extremities>lowers) & sensory loss (all, usually upper>lower), aphasia/L-sided neglect, anosognosia (no knowledge of disease) anterior cerebral a: leg-foot motor/sensory defects; watershed: severe hypotn, proximal limb weakness lateral striate: divisions of MCA that supply basal ganglia; posterior limb of internal capsule=pure motor loss ant. comm. a: most common site of Circle of Willis aneurism, visual field defects; post. comm. a: III palsy ant. circle=motor, aphasia; post. circle=CN deficits, coma, cerebellar deficits, aphasia/unilateral neglect aneurysms: assn w/ ADPKD, Ehlers-Danlos, Marfans, age, htn, smoking, blacks; most commonly hemorrhage ischemia: irreversible after 5m, most sensitive=hippocampus, neocortex, cerebellum, watershed; red neurons (12-48h), necrosis + PMNs (1-3d), macrophages (3-5d), reactive gliosis/vascular prolif (1-2w), glial scar (>2w) ischemia: irreversible after 5m, most sensitive=hippocampus, neocortex, cerebellum, watershed; red neurons (12-48h), necrosis + PMNs (1-3d), macrophages (3-5d), reactive gliosis/vascular prolif (1-2w), glial scar (>2w) 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 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, w/ R MLF damage, R eye doesn't move, L eye has R-beating nystagmus reflexes Achilles=S1-2; patella=L3-4; biceps=C5-6; triceps=C7-8; Moro: abduct/extend limbs when startled, then draw together, gone by 3mo; Babinski: dorsiflexion of big toe, fanning of other toes, if after 15mo=UMN lesion midbrain (III, IV), pons (V-VIII), medulla (IX-XII); lateral=sensory, from alar plate; medial=motor, basal plate nuc of X Solitarius: Sensory; aMbiguus: Motor; dorsal motor: autonomics; PS to lacrimal via VII, pupil via III retinitis: retinal necrosis + edema=atrophic scar; iritis=systemic inflammation; CRAO: acute painless LOV light enters retina, II, bilateral pretectal nuclei, Edinger-Westphal nuclei, III, bilateral pupil constriction Marcus-Gunn: more constriction on consensual reflex than direct (optic n damage, retinal detachment) III: ocular mm output is central (affected by vascular dz), surrounded by PS output (affected by compression) LUQ anopia=Meyer's loop (temporal lobe), LLQ anopia=dorsal optic radiation (parietal lobe); both MCA brain lesions ring-enhancing: mets, abscess, toxo, AIDS lymphoma; uniformly enhancing: lymphoma, mets, meningioma; heterogeneously enhancing: GBM; can cause cingulate (subfalcine) herniation uncal herniation: ipsilateral Horner (stretch III), contralateral homonomous hemianopia (PCA compression), ipsilateral paresis (Kernohan's notch, crus cerebri compression), duret hemorrhages (push brain stem down) dementia Alzheimer's, multi-infarct, Pick's dz, Lewy body dementia, CJD, syphilis, HIV, B12def, Wilson's dz seizure synchronized, high-f firing; partial: 1 area of brain, usually medial temporal lobe, can generalize, can be simple (consciousness intact) or complex; generalized: absence (petit mal, no post-ictal confusion), myo-clonic, tonic-clonic (grand mal), tonic, or atonic; epilepsy: recurrent seizures (non-febrile); in kids: genetic, febrile, trauma, congenital, metabolic; adults: tumor, trauma, stroke, infxn; old: stroke, tumor, trauma, metabolic, infxn; drugs: INH, bupropion, imipenem/cilastatin 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

Psych (dzd=disorder) diseases/NTs anxiety=SONIGO; depression=SODONO; Parkinson's: ODISIA; Schizophrenia: ID; Alzheimer's: OA hospitalism/anaclitic depression: infant depression from to separation, withdrawn/unresponsive baby childhood dzs ADHD: normal intelligence, commonly continue into adulthood, low frontal lobe V; conduct dzd: antisocial personality disorder <18yo; oppositional defiant dzd: no serious violations; Tourette's: assn w/ OCD, movements + tics; separation anxiety dzd: may have factitious physical sx Autism: language/social impairment; Asperger's: social impairment, no cognitive/verbal defects; Rett's: F>M, XL, regression, loss of development/verbal/motor abilities, hand-wringing; childhood disintegrative dzd: multiple areas of regression after 2y of normal development, M>F, usually presents between 3-4yo delerium: acute onset waxing/waning consciousness, visual hallucinations, illusions, abnormal EEG; dementia: gradual decreased cognition, no psychosis, normal EEG, depression=pseudodementia hallucination: no stim; illusion: misinterpretat'n of stim; delusion: false belief; loose ass'n: disordered thought hallucinations audio=schizophrenia, olfactory=aura, tactile=DT/cocaine; hypno-gog-/-pomp-ic: falling/get up 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 related)<1mo2w of stable mood w psychotic sx + a major depressive, manic, or mixed episode dissociative identity dzd: multiple personalities, ass'd w/ sexual abuse; depersonalization dzd: persistent feeling of detachment/estrangement; dissociative fugue: abrupt change in geographic location w/ amnesia bipolar 1 manic (bipolar I) or hypomanic (II) episode, depression always occurs eventually; high suicide risk dysthymia: mild depression, >2yr; cyclothymic dzd: + hypomania, mild bipolar>2yr manic >1wk, pick 3: distractable, irresponsible (hedonism), grandiose, flight of ideas, agitation (high activity level), sleeplessness (no need), talkativeness (pressured speech); hypomanic: no impairment or psychoses depression self-limited, episode lasts 6-12mo, lifetime prevalence: F=20%, M=10%; 2+ wk of pick 5: sleep disturbance (early morning awakening most important), loss of interest (anhedonia, necessary), worthless/ guilt, low energy, low concentration, change in appetite, psychomotor sx, suicidal ideation, depressed mood; MDD: 2 episodes w/ 2mo sx-free; atypical depression: hypersomnia, overeating, mood reactivity; postpartum depression: 15% incidence, depressed affect, anxiety, poor concentration, lasts 2w-2mo; refractory=ECT tx 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 panic dzd recurrent, intense fear, peaks in 10m, pick 4: palpitations, parasthesias, abd distress, N, fear of dying/losing control, light-headed, chest pain, chills, choking, sweating, shaking, SOB, disconnectedness GAD: >6mo, uncontrolled anxiety, sleep disturbance, fatigue, GI sx, difficulty concentrating; adjustment dzd: GAD with specific stressor, usually <6mo; PTSD: reexperiencing traumatic event: acute stress dzd<1mochild abuse) somatoform dzd physical sx, no identifiable cause, unconscious, F>M; somatization: multiple organ system complaints; conversion: pt is aware but indifferent to sx ("la belle indifference"); hypochondria: fear of having serious dz despite tests; body dysmorphic dzd: minor/imagined defect, repeated cosmetic surgery; pain dzd substances dependence: pick 3 in 1yr: tolerance, withdrawal, more than desired, desire to cut down, too much energy spent getting, using, or recovering from, important activities reduced, continued use in spite of insight; abuse: failure to fulfill major obligations, physically hazardous situations, legal problems, CUIS of insight DT: ANS hyperactivity (hi HR, tremor, anxiety, seizure), then psychosis (hallucination, delusion), then confusion

Behavioral Science bias selection: nonrandom group assignment; late-look: inappropriate time for observation; lead-time: early detection confused w/ increased survival; Pygmalion effect: researcher's belief in efficacy changes outcome; Hawthorne effect: group studied changes behavior; sampling: nonrepresentative to pop. (not generalizable) prevention 1°: prevent occurance (vax); 2°: early detection (screening); 3°: reduce disability from dz (tx) reportable dzs: Hep, AIDS, gonorrhea, syphilis, TB, MMR, salmonella, shigella, VZV; HIV varies by state Medicare >65, ESRD, etc; A=inpatient, hospitals, hospice, home health; B=outpatient, drs services, PT/OT; C= combo; D=rxs; Medicaid: health assistance for very low income Advance directives living will: txs refusal (DNR); durable power of attorney: appointing a medical surrogate APGAR (1): appearance (trunk pink), pulse (<100), grimace (2=grimace + cough), activity (some), resp (irregular) sleep spend most time in stage 2 (bruxisms); stage 3-4 (delta)=enuresis, night terror, sleep walking; raphe nuc (5HT) key in initiating; NE reduces REM (depression, decreased latency, increased total, repeated awakening); narcolepsy: starts with REM sleep, can have cataplexy (fainting goats) or hypna-gog/pomp-ic hallucinations

Renal 60% water by wt (40L), 2/3 intracellular, 1/3 ECF (inulin, 1/5 plasma [radiolabeled albumin], 4/5 interstitial) glomerular filtration: fenestrated capillaries (size), podocyte foot processes, fused BM w/ heparin SO4 (charge)

Cx=VUx/Px; GFR=Cinulin

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 pump stimulated by AII, contraction alk]), Cl resorbed paracellular, ammoniagenesis (gln to glu to αKG [broken down & absorbed as 2bicarb] each generates an ammonium ion) 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 ALOH basal: Na/K ATPase, passive K and Cl chs; NKCC (Na/K/2Cl symport), paracellular Mg and Ca resorption DCT basal: Na/K ATPase, Na/Ca antiport (induced by PTH); luminal Na/Cl symport (thiazide) and Ca ch CT principal cell: basal V2R (ADH) inserts aquaporins luminally; ENaC (aldo induced) absorbs Na in exchange for K and H; intercalated cells: α=secretes H (K/H antiport, H ATPase, basal HCO3/Cl antiport), β=backward α RAS renin (from JG): low BP (JG cells), low Na delivery (MD), high β1; ACE: converts AI, degrades bradykinin (vasodilator); AII: vascular smooth mm constriction (BP up), constricts efferent arteriole (raise FF to preserve GFR in low RBF), aldo secretion (increases ENaC, 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

ANP: high atrial P, increases GFR and Na filtration, no compensatory distal Na or water resorption exocrine EPO: secreted by interstitial fibroblasts after peritubular capillary hypoxia, ectopic EPO secretion causes inappropriate absolute polycythemia: HCC, RCC, Wilm's, hydronephrosis; 1,25-D: made by PCT respiratory compensation for MAc: PCO2=1.5(HCO3)+8; for MAlk: PCO2 up 0.7 for every +1 HCO3 acidoses/alkaloses RAc: hypoventilation; RAlk: hyperventilation or aspirin ingestion (early); MAlk: vomiting, diuretics (contraction), 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)

RTAs T1 (distal): α intercalated cell def, inability to secrete H, causes hypokalemia, risk for Ca-stones; T2 (proximal): can be from Fanconi's/expired tetracyclines, PCT bicarb resorption def, hypokalemia, hypoPO4mic rickets (XLD, excess PO4 excretion); T4 (hypoaldo): hyperK causes cellular H/K antiport (make Kout normal causes intracellular alkalosis), inhibits ammoniagenesis (low urine pH & buffering capacity), nAGMAc (mild) casts hyaline: nothing; RBC: GN, ischemia, malignant htn; WBC: tubulointerstitial inflammation, acute pyelo, transplant rejection; granular: ATN; waxy: advanced renal dz/CRF; Bence Jones protein: multiple myeloma RCC: renal tubular cells become polygonal clear cells; vHL, smoking, and obesity; hematuria, mass, flank pain, fever, polycythemia (other neoplastics too: ACTH, PTHrP, PRL); spreads hematogenously (IVC) to bone/lung Wilm's tumor (nephroblastoma): contains embryonic glomerular structures; huge mass, hematuria, WT1 gene (tumor suppressor, 11p) deletion; can be part of WAGR complex (Aniridia, GU malformation, Retardation) transitional CC: painless hematuria=bladder cancer; phenacetin, smoking, aniline dye, cyclophosphamide pyelo acute: affects cortex, spares glomeruli/vessels; fever, CVA tenderness, N/V, WBC casts; chronic: coarse corticomedullary scarring, blunted calyx, dilated/atrophic tubules contain eosinophil casts (thyroidization) 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 diffuse cortical necrosis: cortical infarct of both kidneys, usually DIC (esp pregnancy) and vasospasm ATN: most common cause of ARF in hospital, reversible, fatal if untxed, oliguric phase most dangerous, granular (muddy brown) casts; ass'd w/ ischemia (shock/sepsis), crush injuries (myoglobinuria), toxins papillary necrosis: gross hematuria/proteinuria; assn w DM, acute pyelo, chronic phenacetin use, HbS ARF abrupt decline in renal function w/ high Cr and BUN over days; prerenal: low RBF and GFR (hypotn); renal: usually ATN, less commonly acute GN (RPGN, eg), patchy necrosis causes obstruction and backflow across tubule, low GFR, epithelial/granular casts, impaired resorption; postrenal: bilateral obstruction (BPH, eg) renal failure: Na/water retention, hyperK, MAc, uremia (can cause N/anorexia, pericarditis, asterixis, platelet dysfunction, encephalopathy), anemia, renal osteodystrophy (2° hyperPTH), dyslipidemia (esp hyperTGemia) 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 majora; cardinal L: cervix to pelvis, houses uterine vessels; all within broad L pudendal nerve block given at ischial spine; ureters go under uterine a/ductus deferens (retroperitoneal) ovary=simple cuboidal, uterus=simple columnar, pseudostratified, tubular glands; prostate=* NE causes increased intracellular Ca, smooth mm contraction, vasoconstriction, and antierectile (NO=pro-) Sertoli cells: FSHR (secrete inhibin and ABP [high local T levels]), secrete AMH (sex organ development), maintain blood- testis barrier, support spermatozoa, regulate spermatogenesis; Leydig cells: LHR, secrete T spermatogenesis spermatogonium (maintain germ pool) make 1° spermatocytes, 2° spermatocytes, spermatid; spermiogenesis spermatid to spermatozoa; acrosome=Golgi, flagellum=centriole, middle piece=mitochondria T induces internal structure differentiation from Wolffian duct; DHT: external structures + prostate (UG sinus) M genitalia spermatic cord: 3aa (cremaster, testicular, to ductus deferens), 3nn (genital branch of genito-femoral, sympathetics), 3 fascial layers (cremasteric [int. oblique], external [ext. obl.]/internal [transversalis] spermatic), 3 others (pampiniform plexus, vas, lymphatics); scrotal layers: (some damn englishman called it the testes) skin, dartos, external spermatic fascia, cremaster m, internal, tunica vaginalis/albuginea estrogendevelopment of F 2° sex characteristics, growth of follicle, endometrial prolif, increased myometrial excitability, upregulation of Rs (E, P, LH), stimulates PRL secretion but blocks its effect at breast, increase in transport proteins (SHBG, TBG), increase HDL, lower LDL; LH activates desmolase in theca cells (chlsl to androstenedione), FSH activates aromatase in granulosa cell (androstenedione to E); during pregnancy, estradiol (most potent) and estrone (less) up 50x, estriol (least potent) up 1000x (indicates fetal well-being) progesterone stimulates endometrial glandular secretions, spiral a development, maintains pregnancy, decreases myometrial excitability, makes thick cervical mucous to prevent sperm into uterus, ups body T, uterine tone relaxation (prevents contractions), decrease ER expressivity; at birth, drop in P causes lactation cycle day0=basal endometrial layer, proliferative phase for 2 wk (FSH, follicular growth fastest in wk2), day 14=(LH) ovulation, corpus luteum secretes progesterone; day21: no implantation, corpus regresses, menses polymenorrhea<21d20wk pregnant, ass'd w/ htn, DM, autoimmune dzs, chronic renal dz; impaired vasodilation of spiral aa causes placental ischemia, causing increased vascular tone; other sx: headache, blurred vision, abd pain, altered mentation, hyperreflexia, hyperuricemia, low platelets; tx=delivery, bed rest, salt restriction, MgSO4, diazepam HELLP sz: hemolysis, elevated LFTs, low platelets, VERY BAD (can cause cerebral hemorrhage and ARDS) maternal DM: caudal regression sz (anal atresia/sirenomelia), macrosomia, NRDS, postnatal hypoglycemia ectopic pregnancy: usually in fallopian tubes, high hCG w/ sudden lower abd pain, dx=US; risk=hx of infertility, salpingitis/PID, ruptured appendix, prior tubal surgery, prior ectopic 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 intralobular fibrosis, calcifications common; epithelial hyperplasia: increase in cell layers in terminal duct lobule, >30yo, if atypical cells=increased risk for ca other common conditions acute mastitis: abscess, S. aureus most common, usually during breast feeding; fat necrosis: painless, from injury (usually not reported/remembered); gynecomastia: hyperestrogenism (age, cirrhosis, testicular tumor), XXY, rxs (E, psychoactive drugs, dig, cimetidine, ketoconazole, spironolactone) malignant breast tumors: common post-menopause, from mammary duct epithelium or lobular glands; over-expression of erb-B2 (EGF-R) common; most important prognostic factor=axillary LN involvement; risk factors: high E, older age at first live birth, obesity (adipose tissue has aromatase, so increases E exposure) prostate -itis: dysuria, frequency, urgency, low back pain (acute=bacterial, chronic is usually abacterial); BPH: hyperplasia of lateral/middle lobes, dysuria, frequency, nocturia, hesitancy, high PSA; adenoca: posterior lobe usually, dx by DRE, high PSA, low fraction of free PSA, osteoblastic mets to bone (high alk phos), PAP penis CIS Bowen's dz: gray crusty plaque, 50s, progresses to SqCC <10%; erythroplasia of Queyrat: red velvety plaque; Bowenoid papulosis: multiple papules, younger, usually noninvasive 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 damage, lamellar bodies; lecithin/sphingomyelin>2.0 in amniotic fluid=lung maturity clara: nonciliated columnar, secretory granules (component of surfactant, degrades toxins), reserve aspiration: upright=lower portion of RLL, supine=superior portion of RLL; A to B (artery to bronchus): RALS external intercostals used for active inpiration, fibers point down; other active inspiratory mm: scalene, SCM surfactant: raises compliance (change in V/P, reciprocal of elastance [lowered]), deficient in neonatal RDS Law of Laplace: P favoring collapse=2(surface tension)/r (so low surfactant or low radius tends to collapse) lung produces ACE (inactivates bradykinin) and kallikrein (activates); ACEI causes increased lung bradykinin dead space=TV(PaCO2-PeCO2)/PaCO2; biggest contributor in healthy ppl is apices (fewer deeper breaths better) Hb: taut has low O2 affinity, favored by exercise (increased T, [H], pCO2, altitude, 2,3DPG); 2,3DPG: byproduct of glycolysis, marker 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 CN (prevents cytochrome oxidase dysfunction); thiosulfate then given to bind and excrete renally; can also be formed as a side effect of dapsone; dark blue/brown color carboxyHb: bound to CO, lower binding capacity, L-shift (stays in relaxed form), ETC inhibitor, hyperbaric O 2 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 pulmonary htn: >25mmHg at rest or >35 during exercise, causes atherosclerosis, medial hypertrophy, intimal fibrosis; 1°=inactivating mutation of BMPR2 (normally inhibits smooth m prolif, poor prognosis); 2°=(COPD, mitral stenosis, emboli, autoimmune (diffuse scleroderma), L to R shunt, apnea), causes cor pulmonale alveolar gas eq: PAO2=PIO2-PaCO2/0.8; normally, PIO2=150; A-a gradient=PAO2-PaO2=10-15 (high in hypoxemia from VQ mismatch, shunting, fibrosis); R=respiratory quotient=CO2 produced/O2 consumed hypoxemia=low PaO2, hypoxia=low O2 delivery to tissue (anemia, low cardiac output), ischemia=loss of flow ventilation and perfusion are greater at the lung base, but V/Q=0.6; shunt: 100% O2 doesn't improve PO2 CO2 back to lungs: bound to Hb at N terminus as carbaminoHb (5%), dissolved (5%), bicarb (90%, H produced bound to heme; O2 binding at lung promotes dissociation of H-Hb and CO2 formation [Haldane effect]) DVT: Homans' sign=tender calf on dorsiflexion of foot; Virchow's triad: stasis, hypercoag, endothelial damage COPD chronic bronchitis: mucus-gland hypertrophy (high Reid index), small airway dz, wheezing, crackles, shunting causes early-onset hypoxemia, late-onset dyspnea; emphysema: destruction of alveolar walls, large air spaces, low elasticity, pursed-lip breathing, 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 infxn of bronchi causes permanent airway dilation, hemoptysis, aspergillosis, from CF, Kartagener's 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) Biochem (pathology) XLR diseases (XLD=hypophosphatemic rickets) 2 blood dzs G6PDD Hemophilia (A and B) 2 binomial dzs Lesch-Nyhan Wiskott-Aldrich 2 B's Becker's MD (+DMD) Bruton's agammaglobulinemia 2 O's Ocular albinism OTC deficiency 2 LSDs Fabry's Hunter's

Amino acids (GluM HArV, PITT) Essential Ketogenic Leucine, Lysine Glucogenic Methionine, Valine, Arginine, Histidine Both Phenylalanine, Isoleucine, Threonine, Tryptophan Acidic Glutamate, Aspartate Basic Lysine, Arginine (most basic), Histidine (no charge at body pH)

Lipid transport Particle Chylomicron VLDL IDL Proteins B-48, C-2, E B-100, C-2, E B-100, E LCAT: lecithin-chlsl acyltransferase, in HDL and LDL, esterifies 2/3 of plasma chlsl CETP: chlslester transfer protein, takes chlsl from HDL to LDL/VLDL, TG back to HDL hyperchylomicronemia (I): LPL def or altered apoC-II (cofactor) causes high TG and chlsl; pancreatitis, HSM, eruptive xanthomas, no increased risk for atherosclerosis familial hyperchlslemia (IIa): AD, absent LDL-R causes increased LDL, chlsl, tendon (Achilles) xanthomas, accelerated atherosclerosis (MI<20yo), corneal arcus hyperTGemia (IV): hepatic VLDL overproduction causes increased TG, pancreatitis abetalipoproteinemia: AR, MTP (microsomal TAG transfer protein, loads apoB with lipids) def causes inabilty to synthesize VLDL/chylo; sx: FTT, ataxia, steatorrhea, malabsorption, nyctalopia, acanthocytosis, intestinal biopsy full of lipid

PKU: Phe OHase or THB def, Tyr is essential, screened for 2-3d after birth (normal at birth from maternal enzyme); sx: mental/growth retardation, seizures, musty body odor, fair skin, eczema; maternal PKU: microcephaly, mental/growth retardation, CHD branched/VLCFA cant undergo β-ox, so degraded in peroxisomes (def causes improper CNS myelination)

Embryo Fetal landmarks wk1 d3=morula; d6=blastocyst implantation, hCG secretion begins wk2 bilaminar disk (epi-/hypo-blast), placenta (syncytio-/cyto-trophoblast) wk3 gastrulation/primitive streak; d18=notochord; d21=neural tube closure wk4 heartbeat, limb buds form (4 chambers, 4 limbs) wks3-8 embryonic period: organogenesis, most susceptible to teratogens wk8 fetal period: movement, looks like baby wk10 genitalia have M/F characteristics

Embryologic derivatives surface epidermis, adenohypophysis, lens, salivary/sweat/mammilary glands, ectoderm oral/olfactory epithelium, sensory organs of inner ear neuro- CNS (brain, neurohypophysis, oligodendrocytes, astrocytes, ependymal cells, ectoderm spinal cord), retina neural PNS (incl. chromaffin cells of adrenal medulla), AP septum, pia, arachnoid, skull crest bones, odontoblasts, C-cells of thyroid, melanocytes Vertebral, Anal atresia, Cardiac, Tracheo-Esophageal fistula, Renal, Limb; bone, meso-derm mm, connective tissue/dura, spleen, GU, Eustachian tube

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 Bacteria pus, empyema, abscess S. aureus asplenic/Sickle cell Capsule, esp S. pneumo, H. flu, N. meningitides pneumonia in CF, burn infxn Pseudomonas aeruginosa traumatic open wound C. perfringes (gas gangrene) surgical wound S. aureus dog/cat bite Pasteurella multocida currant jelly sputum Klebsiella PAS Trophyerma whippelii meningitis/sepsis in newborn S. agalactiae (group B) health care provider HBV (needle stick) fungal infxn in DM Mucor/Rhizopus chronic granulomatous dz catalase (+): S. aureus, Nocardia, Aspergillus neutropenic patients Candida (systemic), Aspergillus bilateral Bell's palsy Borrelia burgorferi (Ixodes, so is Erlichia & Babesia) stroke w/o htn syphilis pediatric infxn (incl. epiglotitis) H. flu oral infxn, branching rods, sulfur granules Actinomyces israelii

Parasites brain cysts, seizures Taenia solium (cysticercosis) liver cysts Echinococcus granulosus B12 def Diphyllobothrum latum biliary tract dz, cholangioca Clonorchis sinensis hematuria, SqC bladder cancer Schistosoma hematobium portal htn Schistosoma mansoni hemoptysis Paragonimus westermani microcytic anemia Ancyclostoma, Necator perianal pruritis Enterobius (pinworms) periorbital edema/m inflamed Trichinella spiralis hyperpigmentation, blindness Onchocerca volvulus Protozoa horseshoe-crab shaped Giardia or Trichomonas liver abscess Entamoeba fever, HSM, pancytopenia Leishmania

Pneumonia neonates children adults S. agalactiae S. pneumo S. pneumo E. coli RSV/other viruses C. pneumo C. pneumo M. pneumo M. pneumo H. flu anaerobes/viruses

Meningitis neonates children adults S. agalactiae S. pneumo S. pneumo E. coli enteroviruses enteroviruses L. monocytogenes N. meningitides N. meningitides H. flu (unvax'ed) HSV meningism (nuchal rigidity, photophobia, headache), Kernig's sign (flex hip, rigidity on knee extension), Brudzinski's sign (prone, head lifted, feet lift involuntarily) Immune HLA/disease associations A3 Hemochromatosis DR3 DM type I B8 Graves' Dz DR4 RA, DM type I B27 Sero(-) spondyloarthropathies DR5 pernicious anemia, Hashimoto's DR2 hay fever, anti-GBM, SLE, MS DR7 steroid-responisve nephrotic sz

Cytokines (Mnemonic: "Hot D8, My GoodnEss, A Hot/Cute Lynn Comes") IL-1 MP pyrogen, induces endothelial adhesion molecules/chemokines IL-2 Th1 activates CD8 (signal 2) IL-3 TCs hematopoietic cells to become myeloid precursors IL-4 Th2 differentiation to Th2, and class switching to IgG and IgE IL-5 Th2 differentiation of BC, class switch to IgA, eosinophil maturation IL-6 MP/Th2 pyrogen, induces acute phase reactants IL-7 lots hematopoietic cells to become lymphoid precursors IL-8 MP chemotactic IL-9 Th2 acts on hematopoietic cells, anti-apoptotic, pro-growth IL-10 Th2, Treg activates Th2, inhibits activated TC and Th1 IL-11 ? hematopoietic cells to become megakaryocytes, bone prolif IL-12 MP, BC differentiation to Th1, activates NK TNF-α MP mediates septic shock, activates endothelium, leaky IFN-γ Th1 activates macrophages and Th1, inhibits Th2, ups MHC1 and 2

AutoAbs and associated disorder anti- dz anti- histone drug-induced lupus glu decarboxylase IgG RA gliadin/endomysial Scl-70 scleroderma (diffuse) centromere U1-RNP mixed connective tissue microsomal/thyroG smooth m autoimmune hepatitis mitochondrial BP-180 bullous pemphigoid desmoglein Jo-1 polymyositis/dermatomyositis c-ANCA

Path Amyloid: β-sheet, Congo red stain, apple green birefringence, gross=waxy Primary AL from Ig light chains (multiple myeloma, BJ proteins) Secondary AA serum amyloid-ass'd protein (chronic inflammation) Senile cardiac AF from transthyretin DM type 2 AE from amylin thyroid medullary ca A-CAL from calcitonin Alzheimer's β-amyloid from amyloid precursor protein dialysis-associated β2-μG from MHC I proteins

Oncogenes: one mutation needed Tumor suppressors: two mutations needed gene tumors (gene product) gene tumors (gene product) abl (9) CML (TK) Rb (13q) retinoblastoma, osteosarcoma bcl-2 follicular, undiff. lymphomas p53 (17p) most cancers, Li-Fraumeni Sz HER-2 or breast, ovarian, and gastric BRCA1 (17 q) breast and ovarian cancer erb-B2 adenocarcinomas (TK) HER-2 or breast, ovarian, and gastric erb-B2 adenocarcinomas (TK) BRCA2 (13 q) breast ca (DNA repair protein) ras colon cancer (small GTPase) p16 (9p) melanoma c-myc Burkitt's lymphoma (TF) APC (5q) colorectal cancer (assn w/ FAP) l-myc lung tumor (TF) WT1 (11p) Wilms' tumor n-myc neuroblastoma (TF) NF1 (17q) NFM type 1 ret MEN 2A and 2B (TK) NF2 (22p) NFM type 2 c-kit GIST (cytokine receptor) DPC (18q) pancreatic cancer DCC (18q) colon cancer

(heart is mostly β1, M2) GP-linked 2nd messengers α1 (q) vascular smooth m contraction (1B), sphincter m contraction, mydriasis α2 (i) decrease sympathetic outflow and insulin release β1 (s) increases HR, contractility, lipolysis, renin release β2 (s) same as β1 (insulin, not renin), vaso-/broncho-dilation, drops uterine tone M1 (q) in CNS, postsynaptic autonomic ganglia, gastric (ECL)/salivary secretion M2 (i) decrease HR and contractility of atria M3 (q) gut peristalsis, bladder contraction, eye (miosis, accomodation), bronchoconstriction, increased exocrine secretion (DUMBLS) D1 (s) relaxes renal vascular smooth m, brain D2 (i) esp in brain, modulates transmitter release H1 (q) increased mucous production, bronchiole contraction, pruritis, pain H2 (s) increased gastric acid secretion V1 (q) increased vascular smooth m contraction V2 (s) increased water reuptake in collecting tubules of kidney

Murmurs Type Timing Loudest Radiation Increased intensity mitral |===| apex axilla hi TPR (squatting), hi regurg LV return (expir) TR |===| LSB RSB hi RV return (inspir) MVP most | c<| apex midsys low venous return, hi common click TPR (hand grip) aortic |<>| late aortic carotids or louder w/ squatting, stenosis peak=bad apex softer w/ Valsalva MS | | s== apex open snap hi LA return (expir) AR/PR | |<>== LSB bounding lower w vasodilator pulses (AR) VSD |===| tricuspid harsh PDA |===|===S2 machine-like

Angina/MI ST-dep angina, subendocardial infarct ST-elev Prinzmetal's angina, transmural infarct Stage Age Criteria Early mins tall T, normal ST and R Stage I <6hr STE (tombstone), R nl, small Q Intermed >6hr STE, T-inversion, Q, loss of R Stage II days T-inversion, Q, ST normalizes Stage III residual persistent Q, loss of R, T nl

Localizing MI using ECG (gold standard w/i 6h)

I | II III | aVL aVF | rV4 V1 | V2 apical (LAD) + | | + | + | + anteroseptal (LAD) | | | + | + anterolateral (LCX) + | | + | | posterolateral (LCX) | + | + | | inferior (RCA/PD) | + + | + | | RV (acute marginal) | + | + | + + | +

MI markers troponin I most specific (also PE, myocarditis), rises after 4h, peak 12h, stays 7-10d CK-MB non-specific, good for reinfarction on top of acute MI, gone by 3d AST least specific, peaks at 2d, stays for a while Evolution Age Microscopic Changes Gross day 1 4h: early coagulative necrosis; 12-24h: dark, mottled, pale w contraction bands, early PMN infiltrate tetrazolium dye day 2-4 extensive coagulative necrosis, acute hyperemic inflammation in tissue surrounding infarct, dilated vessels, PMN infiltrate day 5-10 ingrowth of granulation tissue as macro- hyperemic border, phages degrade old structure and induce centrally yellow-brown scar formation wk 7 scar grey white

Endocrine Signalling pathways of hormones cAMP Ca (PTH, calcitonin), ADH (V2R)/α-subunits (FSH, LH, TSH, β-hCG), melanotropic (ACTH, MSH), pancreatic (glucagon), GHRH

cGMP NO, ANP IP3 α-subunitRH (GnRH, TRH), posterior pit (oxytocin, ADH) nuclear T3/T4 cytosolic all steroids but T3/4: DHT, P, E2, D3, cortisol, aldo 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 receptor TK (JAK/STAT) GH, PRL, IL's, CSF

DM dx HbA1C Fasting glucose Normal <6.0% <110 Pre-diabetic 6.0-6.4% 110-126 Diabetic >6.5% >126 or sx of hyperglycemia and a casual (random) plasma glucose >200

CAH (all have enlarged adrenal glands due to low cortisol and thus high ACTH) Deficiency Epidem Sex Hrmns Aldo BP Other 21-OHase 95% high low low hypovolemic shock in newborn 11βOHase 5% high low high masculinization, as w 21-OHase 17αOHase rare low high high M=pseudoherm, F=sexual infant

Multiple endocrine neoplasias (MEN) MEN 1 (Wermer's) parathyroid (kidney stones), pituitary (usually PRL or GH), and pancreas tumors (Zollinger-Ellison, so stomach ulcers) MEN 2A (Sipple's) medullary thyroid cancer, pheo, parathyroid (kidney stones) MEN 2B medullary thyroid cancer, pheo, oral or intestinal ganglioneuromatosis (marfanoid habitus) MEN 2A and MEN 2B associated w/ ret gene (oncogene, tyrosine kinase)

T3/T4: synthesized by peroxidase from I + tyrosine (inhibited by anions and PTU or methimazole); bone growth, CNS maturation, increased β1 in heart, increased metabolic rate; TBG increases in OCP-use and pregnancy hyperT3 pretibial myxedema; toxic multinodular goiter: hot nodule, mutated TSH-R, rarely malignant; Grave's: presents during stress, type II hypersensitivity; thyrotoxicosis: complication of hyperT3, stress-induced catecholamine surge, death by arrhythmia; Jod- Basedow: thyrotoxicosis if a pt w/ I-def goiter is made I-replete hyperT3 pretibial myxedema; toxic multinodular goiter: hot nodule, mutated TSH-R, rarely malignant; Grave's: presents during stress, type II hypersensitivity; thyrotoxicosis: complication of hyperT3, stress-induced catecholamine surge, death by arrhythmia; Jod- Basedow: thyrotoxicosis if a pt w/ I-def goiter is made I-replete

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, pale, puffy faced, protruding umbilicus, protuberant tongue; subacute thyroiditis (de Quervain's): self-limited, following flu-like illness, jaw pain, early inflammation (granulomatous), tender; Riedel's thyroiditis: replaced by fibrous tissue, rock-hard thyroid cancer papillary: most common, excellent prognosis, "Orphan Annie" nuclei (ground glass), nuclear grooves, psammoma bodies; follicular: uniform follicles, good prognosis; medullary: from C cells, sheets in amyloid stroma, assn w/ MEN2A/B; undifferentiated/anaplastic: very poor; lymphoma: assn w/ Hashimoto's low T4 to T3: PTU, glucocorticoids, amiodarone, iopanoate, non-selective β-blockers

GI GI hormones/secretions Hormone Source Regulation Action gastrin G cells up: AAs, peptides, up: (ECL) gastric H+ (antrum) stomach distention/ secretion, mucosal alkalinizat'n, vagal growth, motility, & stimulation (GRP) parietal hyperplasia secretin S cells (D) up: acid/FAs in up: bile and panc duodenum bicarb secretion; down: H+ secretion GIP K cells up: FA, AAs, oral up: insulin secret'n; (D/J) glucose down: H+ secretion CCK I cells (D/J) up: FA, AAs up: panc secretion, GB contract'n, tone of pyloric sphincter somato- δ cells up: acid; down: vagal down: everything statin (panc/GI) stimulation VIP paraS up: distention, vagal up: sphincter relax- ganglia stimulation ation, water excret'n Motilin Sm bowel up: fasting state makes MMCs intrinsic parietal B12 binding protein factor cells (uptake in ileum) gastric acid parietal up: M3R (ACh), H2R, decreases stomach pH cells gastrin; down: SS, GIP, PG, secretin pepsin chief cells up: local H+, vagal protein digestion stimulation bicarb mucosa, up: secretin (acts on neutralize acid Brunner's pancreatic and biliary glands secretions) IBD Crohn's (disordered response to flora) UC (autoimmune) Location usually terminal ileum, skip lesions, rectal continuous, always involves rectum sparing Gross cobblestone mucosa, creeping fat, bowel wall friable mucosal pseudopolyps, loss thickening, linear ulcers/fistulas of haustra Micro- transmural inflammation, noncaseating sub-/mucosal inflammation only, scopic granulomas, lymphoid aggregates crypt abscesses/ulcers Complic- malabsorption, strictures, fistulas, colo-rectal malnutrition, toxic megacolon, ations cancer (minorly increased risk) colorectal carcinoma (hi risk) Sx diarrhea ± blood, erythema nodosum, bloody diarrhea, PSC, pyoderma migratory polyarthritis, immunologic gangrenosum, ankylosing disorders spondylitis, uveitis tx corticosteriods, infliximab ASA, 6-MP, infliximab, colectomy drugs causing GI path: macrolides=acute cholestatic hepatitis; INH=hepatitis; hepatic necrosis: halothane, valproate, acetaminophen, Amanita mushroom poisoning GI pathology Marker Use Aminotransferases hepatocyte damage (virus: ALT>AST; alcohol: AST>ALT), MI (AST) GGT (glut cholestasis, >2x ULN transpep- w/ heavy EtOH tidase) consumption alk phos bone dz, cholestasis (biliary dz/obstruc- tion, macrolides) amylase acute panc, mumps lipase acute panc (specific) Jaundice pre-HC (hemolysis) hepatocellular conj blood bilirubin low (all unconj) some (some unconj) urine bilirubin low (not soluble) high (some conj) urine bilinogen high nl/low heme to unconjugated bilirubin in macrophage, albumin carries (complex=indirect bilirubin) to liver, conjugated by UDP glucuronyl transferase to direct bilirubin, into biliary lumen by glucuronyl transferase, and broken down in gut to urobilinogen

pancreatitis acute: autodigestion; obstruction (gallstones, ERCP), overworked (EtOH, hypercalcemia, hyperTGemia), mumps, trauma, autoimmune, drugs (sulfa, steroids); sx: epigastric abd pain radiating to back, anorexia, N, elevated lipase (more specific) and amylase; can cause DIC, ARDS, diffuse fat necrosis, hypoCa, pseudocyst, infxn, hemorrhage, multiorgan failure; chronic: can cause pancreatic insufficiency (ADEK deficiency, steatorrhea, DM), calcified assoc'd w/ EtOH, smoking, pancreatic cancer pancreatic adenoca: CEA and CA-19-9 markers, NOT assoc'd w/ EtOH; sx: abd pain radiates to back, weight loss, Trousseau's, jaundice, palpable GB (Courvoisier's sign) acute calculus cholecystitis: obstruction, chemical irritation, mucous disruption, bile acid attack on mucosa, PG release, hypomotility, distension, ischemia, bacteria

Heme/Onc Hemolytic anemia (high LDH) Intravascular: low haptoglobin, Hb in urine, not usually jaundiced G6PDD trigger: fava beans, infxn, INH, sulfa, anti-malarial, aspirin, ibuprofen, nitrofurantoin; back pain, Heinz bodies, and bite cells PNH glycophosphatidyl inositol links decay accelerating factor onto RBC membrane, prevents complement cascade; high urine hemosiderin angio- schistocytes; micro-: from DIC, HUS (Shiga toxin), SLE, malignant htn; macro: pathic prosthetic valves, aortic stenosis infxn malaria, Babesia Extravascular: cleared in spleen; high unconjugated bilirubin, jaundice; (Wilsons) sickle cell glu to val on β gene; marrow expansion, aplastic crisis (B19), bone crises, renal (HbS) papillary necrosis/microhematuria, splenic sequestration crisis, autosplenectomy (Howell-Jolly bodies, Salmonella osteomyelitis) HbC def glu to lys, compound heterozygotes w/ HbSC have milder dz than HbSS sphero- hereditary def in cytoskeletal elements (ankyrin, band 3.1, spectrin); high MCHC, cytosis high RDW, SM, aplastic crises; tx=splenectomy (Howell-Jolly body) PK def AR, pyruvate kinase def, low ATP, rigid RBC membrane; HA in newborn auto- spherocyte; warm=IgG: SLE, CLL, α-methyldopa; cold=IgM: CLL, mono, M. immune pneumo; hydrops fetalis; usually Coomb's positive (direct=anti-IgG Ab)

Hemoglobin types Variant Make-up When present

HbA α2β2 normally 95% of Hb

HbA1C α2β2 non-enzymatic glycation of normal Hb, <6%, higher in DM

HbA2 α2δ2 normally 3% of Hb, higher in beta-thal minor C HbC α2β 2 beta variant, mild hemolytic anemia E HbE α2β 2 beta variant, mild hemolytic anemia

HbF α2γ2 normal in fetal, higher in sickle cell

Barts γ4 alpha-thal S HbS α2β 2 beta variant, sickle cell

Gower 1 ζ2ε2 early embryonic stage

Gower 2 α2ε2 late embryonic stage

Lab values in anemia: primary cause in red Serum Fe Transferrin or TIBC Ferritin ("tissue need") (storage) Fe deficiency low high low chronic dz low low high hemochromatosis high low high pregnancy/OCPs nl high nl lead poisoning high low nl Pb poisoning: microcytic/sideroblastic anemia, basophilic stippling of RBCs, renal, GI dz; kids: neuro deterioration, wrist/foot drop, Pb lines on gums/long bones (XR), abd pain; adults (usually work-related): headache, memory loss, demyelination

Translocations Leukemia/lymphoma AML M3 CML Burkitt's Follicular Translocation t(15;17) t(9;22) t(8;14) t(14;18) Activated product - bcr-abl c-myc bcl-2

Polycythemia primary cause in red

plasma V RBC mass O2 sat EPO relative low nl nl nl appropriate absolute nl high low high inappropriate abs. nl high nl high polycythemia vera high high nl low

Musculoskeletal Upper extremity nerve lesions Nerve Root Motor Deficit Sensory Deficit Axillary C5-6 shoulder abduction over shoulder (deltoid) MusCutan C5-7 elbow flexion lateral forearm Radial C5-8 extensors, brachio- posterior arm, dorsal radialis, supinator hand/thumb Median C5-T1 thumb opposition, dorsal + palmar (distal) lateral MCP flex'n lateral 3 1/2 fingers Median C5-T1 + lateral DIP/PIP dorsal + palmar (proxim.) flexion, wrist flex'n lateral 3 1/2 fingers Ulnar C8-T1 interossei, thumb adduction, lumbricals 4 and (distal) 5; sensory: medial 1 1/2 fingers Ulnar C8-T1 + wrist flexion medial 1 1/2 fingers (proxim.) Klumpke C8-T1 +all lumbricals; sensory: medial forearm Lower extremity nerve lesions Nerve Root Motor Deficit Sensory Deficit Obtruator L2-4 thigh adduction medial thigh Femoral L2-4 flex thigh, extend leg ant./medial thigh Common L4-S2 foot eversion/dorsi- anterolateral leg, peroneal flexion, toe extens'n dorsal foot Tibial L4-S2 foot inversion/plan- sole of foot tarflexion, toe flex'n In. gluteal L5-S2 hip extension (stairs) - S. gluteal L4-S1 Trendelenburg -

Bone tumors Benign Epidem. Description osteochondroma M, <25yo most common benign bone tumor; mature bone w/ (exostosis) cartilage cap; from metaphyses; transformation rare enchondroma M, <25yo intramedullary bone, usually distal extremities osteoid osteoma M, <25yo trabeculae of woven bone surrounded by osteoblasts (lytic), <2cm, usually proximal tibia/femur osteoblastoma M, <25yo trabeculae of woven bone surrounded by osteoblasts, >2cm, usually in vertebrae osteoclastoma (giant 20-40yo epiphyseal plates of long bones (esp knee); locally cell tumor) aggressive; XR='soap bubbles'; spindle-shaped cells osteoma Gardner's new piece of bone growing on another, often in skull Malignant Epidem. Description osteosarcoma M, 10-20; 2nd most common 1° malignancy (MM); XR=Codmans (osteogenic sarcoma) bad prog. triangle or sunburst pattern, from metaphyses (esp knee); risk: Paget's, bone infarcts, radiation, Rb Ewing's sarcoma M, <15yo extremely aggressive, early mets, chemo-responsive; XR=onion-skin; anaplastic small blue cells, t(11;22) chondrosarcoma M, 30-60 may be from osteochondroma; intramedullary

Arachidonic acid products

PGE1 keeps PDA open; misoprostol=agonist

PGE2 up: pain, uterine tone, temperature; down: vascular tone

PGI2 "prostacycline", down: platelet aggregation, vascular tone, uterine tone

TXA2 up: platelet aggregation, vascular tone

LTB4 neutrophil chemotaxis

LTC/D/E4 up: smooth m tone, vascular tone/permeability, bronchial tone (-lukast=I)

Infectious derm impetigo honey-crusting, very superficial, highly contageous cellulitis acute, painful, dermal and subcutaneous tissues necrotizin deeper tissue injury, causes crepitus (from methane and fasciitis CO2)

SJS-TEN: anti-psychotic/anti-epilepsy (ethosuxamide, lamotrigine, carbamazepine, phenobarbital, phenytoin), abx (sulfa, PCN), anti-gout (allopurinol), analgesics (NSAIDs), NNRTIs (efavirens, nevirapine); Nikolski's sign, mucosal involvement Neuro Spinal cord: inferior is lateral to superior on LCST and STT Tract/Function 1st Order Neuron/Synapse 2nd Order/Synapse/3rd Order Dorsal column/ medial sensory n ending, cell body in 2=decussates in medulla, ascends lemniscus (ascending dorsal root ganglion, ascends contralaterally in medial lemniscus; sensation), from alar ipsilateral dorsal column; S=VPL of thalamus; 3=sensory plate (embryo) S=ipsilateral nucleus cuneatus or cortex gracilis (medulla)

Spinothalamic tract sensory n ending (C and Aδ), cell 2=decussates at anterior white (ascending pain and body in dorsal root ganglion, commisure, ascends temperature) enters spinal cord; S=ipsilateral contralaterally; S=VPL of thalamus; gray matter 3=sensory cortex lateral corticospinal UMN: cell body in 1° motor first synapse=cell body of anterior tract (voluntary cortex, descends ipsilaterally in horn (spinal cord); LMN: leaves motion), from basal internal capsule, decussate at spine, to NMJ (synapse 2) plate (embryo) pyramid (caudal medulla), descends contralaterally

sympathetics to cell body in hypothalamus, 2=ascend on internal carotid; pupillary dilator m descend in the cord; S=lateral S=sup. cervical ganglion; 3=int. horn at T1 carotid to long ciliary n (V1)

Hemorrhages epidural will cross falx, tentorium, not suture lines, rapid expansion subdural bridging v rupture, elderly/shaken baby, crescent-shaped subarachnoid worst headache of life, ruptured aneurysm, yellow/red spinal tap, vasospasm 2-3d later (blood breakdown products, tx=CCB)

Spinal cord lesions poliomyelitis mucosa to blood to CNS, destroys anterior horn; nonspecific sx going to LMN signs; virus recovered from stool or throat Werdnig-Hoffman AR, degeneration of anterior horns, floppy baby, young death syringomyelia anterior white commissure lesion, usually C8-T1; assn w Chiari Tabes dorsalis 3° syphilis, dorsal root and column degen; locomotor/sensory ataxia, Charcot joint, shooting pain, no DTRs, positive Romberg B12 neuropathy or demyelination of lateral corticospinal, spinocerebellar, and doral vitamin E deficiency columns; ataxic gait, hyperreflexia, impaired vib/position Friedreich's ataxia staggering, frequent falls, nystagmus, dysarthria, pes cavus, hammer toes, HCM (cause of death), childhood kyphoscoliosis anterior spinal a. spares dorsal columns and posterolateral tract (of Lissauer); upper occlusion thoracic ASA is watershed (a of Ademkiewicz below T8) ALS both UMN and LMN signs, no sensory, cognitive, or oculomotor defects, can be from superoxide dismutase 1; tx=Riluzole MS: immunosup- autoimmune inflammation and demyelination of CNS, white F, 20-30; pression and β-IFN scanning speech, intention tremor, MLF sz (internuclear ophthalmolegia), incontinence, nystagmus, optic neuritis, hemisensory/paresis, relapsing/remitting; MRI for dx, high IgG in CSF (oligoclonal bands=dxtic), periventricular plaques (oligodendrocyte loss, reactive gliosis, axon preservation) MS: immunosup- autoimmune inflammation and demyelination of CNS, white F, 20-30; pression and β-IFN scanning speech, intention tremor, MLF sz (internuclear ophthalmolegia), incontinence, nystagmus, optic neuritis, hemisensory/paresis, relapsing/remitting; MRI for dx, high IgG in CSF (oligoclonal bands=dxtic), periventricular plaques (oligodendrocyte loss, reactive gliosis, axon preservation)

Brain tumors 50% are mets; presentation due to mass effect (seizure, dementia, etc) Childhood d Craniopharyngioma supratentorial, benign, confused w/ pit adenoma, calcifications Pilocytic astrocytoma well circumscribed, low grade, cystic + solid, GFAP [+], may be supratentorial; Rosenthal fibers: eosinophilic corkscrews Medulloblastoma malignant, primitive neuroectoderm, can compress 4th ventricle (radiosensitive) (hydrocephalus); pseudorosettes or rosettes, small blue cells Ependymoma poor prognosis, usually 4th ventricle (hydrocephalus); blepharoplasts (rods, basal ciliary bodies), pseudorosettes Hemangioblastoma can produce EPO, ass'd w/ vHL; foamy cells, highly vascular Adult d GBM (grade IV most common 1°, cerebral hemispheres, can cross corpus, GFAP [+]; astrocytoma) pleomorphic, pseudopalisading, around areas of necrosis Meningioma from arachnoid cells, whorled spindle cells, psammoma bodies Schwannoma commonly on VIII (esp NFM), resectable, S-100 [+] Oligodendroglioma rare, slow growing, frontal lobe; chicken-wire capillary pattern surrounding fried egg cells, can be calcified Pit adenoma usually PRL, hyper/hypo-pit, bitemporal hemianopia Demyelinating dzs (also Charcot-Marie-Tooth) PML oligodendrocyte destruction, assc'd w/ JC virus, 2-4% of AIDS, rapidly fatal metachromic AR lysosomal storage dz, arylsulfatase A def, buildup of sulfatides, leukodystrophy impaired production of myelin sheath acute disseminated (post-infxous) perivenular inflammation and demyelination, after infxn encephalomyelitis (VZV, measles) or vax (rabies, smallpox)

vertigo peripheral: more common, positional testing=delayed horizontal nystagmus; central: brain stem/cerebellum, testing=immediate nystagmus, any direction

(dzd=disorder) Ego defenses Pathologic conversion manifestation as physical sx (grief causes "blindness", hysteria) denial, delusional/extreme projection, distortion, splitting (all good/all bad) Immature projection impulses attributed to external source fixation remaining partially at a more childish level acting out, fantasy, idealization, identification (modeling after power, not admiration) Neurotic displacement feelings transferred to safer outlet, scapegoating regression going back to childish level dissociation, rationalization (excuses), isolation of affect, repression, rxn formation Mature suppression voluntary withholding from conscious awareness sublimation unacceptable impulses in an acceptable way (aggression/boxer) humor, altruism

Personality dzds (weird, wild, worried) Cluster A: odd/eccentric, no meaningful relationships; assc'd w/ schizophrenia Paranoid pervasive distrust, projection Schizoid voluntary social withdrawal, limited emotional expression Schizotypal + eccentric beliefs/appearance, magical thinking, awkward Cluster B: dramatic, emotional; associated w/ mood disorders and substance abuse Antisocial disregard for rights of others, criminal, M>F >18, (conduct dzd) Borderline unstable, impulsive, self-mutilating, emptiness, F>M; splitting Histrionic excessively emotional, attention seeking, overly sexual Narcissistic grandiose, sense of entitlement, lacks empathy Cluster C: anxious, fearful; associated w/ anxiety dzds Avoidant hypersensitivity to rejection, inhibited, desires relationships OCPD perfectionist, ego syntonic (OCD=dystonic, ass'd w Tourette's) Dependent submissive, clingy, low self confidence

Psych txs EtOH withdrawal/cocaine OD BDZ ADHD methylphenidate, amphetamines (dexedrine) schizophrenia antipsychotics Tourette's antipsychotics (esp haloperidol) depression SSRIs, SNRIs, TCAs atypical depression MAOIs, SSRIs depression + insomnia Mirtazapine bipolar dzd stabilizers (valproate, Li, carbamazepine), atypicals anorexia/bulemia SSRIs anxiety BDZ, buspirone, SSRIs OCD SSRIs, TCAs, BDZs PTSD SSRIs social phobia SSRIs

Behavioral Science Early developmental milestones Infant <3mo rooting reflex orients to voice 3-6mo holds head up, Moro reflex disappears social smile 6-9mo sits alone, crawls stranger anxiety 12mo walks, Babinski disappears separation anxiety, few words Toddler 1-2yr climb stairs, stack 3-6 blocks object permanence, 200 words 2-3yr stack 6-9 blocks, toilet training gender identity, parallel play Preschool 3-4yr rides tricycle, copies line drawing 900 words, complete sentences 4yr cooperative play, imaginary friends, grooms self, buttons and zips Tanner 1=childhood; 2=adrenarche (pubic hair, breasts); 3=hair darkens, curls, penis longer; 4=penis wider, scrotum darkens, raised areolae; 5=adult, areolae not raised circadian rhythm driven by suprachiasmatic nuc of hypothalamus, regulated by light

Renal Electrolyte disturbances Low High Na disorientation, stupor, coma irritability, delirium, coma K EKG changes (U-waves, flat T's), EKG changes (peaked T's, wide QRS), arrhythmia, paralysis arrhythmias Ca tetany, NM irritability delerium, renal stones, abd pain, stupor Mg NM irritability, arrhythmias delerium, low DTRs, cardiopulm arrest PO4 (IP) osteomalacia renal stones, metastatic calcifications Nephrotic lost heparin sulfate causes massive proteinuria (>3.5g/d, thromboemboli, hyperlipidemia, edema), fatty casts, can lose Igs (infxn risk); FSGS: most common GN in adults and HIV pts; Minimal 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-dome"; MPGN: can be nephritic too, type 1="tram track" (HBV/HCV related), type 2=dense deposits (EM, assc'd w/ C3 nephritic factor); diabetic glomerulonephropathy: non-enzymatic glycosylation (NEG) of GBM causes thickening and increased permeability, NEG of efferent increases GFR causing mesangial expansion, nodular glomerulosclerosis (KW lesions)

Nephritic inflammation of glomeruli causes (PHAROH) proteinuria (<3.5g), hematuria, azotemia, RBC casts, oliguria, htn; IgA nephropathy (Berger's dz): increased IgA synth, often presents after URI or acute gastroenteritis, assc'd w/ Henoch-Schonlein; acute poststrep (postinfxous): in kids, glomeruli enlarged/hypercellular, "lumpy-bumpy", periorbital/peripheral edema, resolves spontaneously; rapidly progressive (crescent) GN: crescents of fibrin, plasma proteins, parietal cells, monocytes, & macrophages, poor prognosis, from Goodpastures, Wegeners, or microscopic polyangiitis; Alport's: split BM; diffuse proliferative: from SLE or MPGN, "wire-looping" of capillaries

Immune deposits Sub-epithelial Sub-endothelial Mesangial Membranous GN (DMGN) Cryoglobulinemia Berger's Dz (IgA nephropathy) Postinfectious GN MPGN Immunofluorescence Pattern Granular Linear Light and Dark Areas Membranous GN Goodpastures Berger's Dz (IgA nephropathy) Postinfectious GN MPGN Other Characteristics Diffuse glomerular proliferation Low Complement Postinfectious GN Postinfectious GN MPGN MPGN SLE Cryoglobulinemia

Kidney stones Ca CaOx most common, can be from ethylene glycol or vit C abuse; hyperPTH

NH4MgPO4 infxn w/ urease bugs (Proteus, eg), can be staghorn, worse w/ alkaluria Urate radiolucent, strong assn w/ hyperuricemia (gout, B3), high cell turnover Cystine hexagonal crystals, usually 2° to cystinuria, tx=alkalinize urine ARF (acute kidney injury) U(Osm) U(Na) FeNa Serum BUN/Cr Prerenal >500 <10 <1% >20 Renal <350 >20 >2% <15 Postrenal <350 >40 >4% >15 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 Placental pregnancy complications Abruptio 3rd trimester, painful bleeding; premature detachment of placenta; fetal death, placenta can cause DIC; risk: smoking, htn, cocaine use Abruptio 3rd trimester, painful bleeding; premature detachment of placenta; fetal death, placenta can cause DIC; risk: smoking, htn, cocaine use Placenta any trimester, painless bleeding; placental attachment to lower uterine segment, previa may occlude os; risk: multiparity or prior C-section Placenta after delivery, massive bleed; defective decidua (placental attachment to accreta myometrium), no separation; risk: prior C-section, placenta previa Retained after delivery, may cause hemorrhage endometriosis: ectopic endometrial glands, nonneoplastic, cyclic bleeding/pain or chocolate cysts, usually in ovary/peritoneum; adenomyosis: w/i myometrium endometrial hyperplasia (excess E, sx=postmenopausal bleeding; risk=anovulatory cycles, HRT, PCOS, granulosa cell tumor) biggest risk for endometrial carcinoma endometrial carcinoma: most common gynecologic malignancy; sx=vaginal bleeding; risk=obesity, DM, htn, nulliparity, late menopause, PCOS, endometrial hyperplasia myometrial tumors leiomyoma=fibroid, most common tumor in F, usually multiple, well- demarcated, benign, E-sensitive (grows w/ pregnancy), 30yo; asxatic, abnormal uterine bleeding, Fe def anemia, miscarriage; whorled pattern of smooth mm bundles; leiomyosarcoma: irregular shape, necrosis, recur, aggressive, usually middle-aged anovulation PCOS, obesity, HPO abnormalities, POF (menopause before 40, follicular atresia), hyperPRL, thyroid/eating dzd, Cushing's, adrenal insufficiency PCOS: high LH causes anovulation, hyperandrogenism (androstenedione from theca cells); low FSH, high T, enlarged bilateral cystic ovaries, amenorrhea, hirsutism, and obesity; assn w insulin resistance; higher risk of endometrial cancer cysts follicular cyst=unruptured Graffian follicle; corpus luteum cyst=hemorrhage into persistent CL, regresses spontaneously; theca-lutein cyst=bilateral/multiple, from Gn stimulation, assn w chorioca and moles; chocolate cysts=endometriosis Ovarian tumors: Germ cell (most common in adolescents) Teratoma 90% of ovarian germ cell tumors; cells from 2-3 germ layers; mature=benign, immature=aggressive; struma ovarii=hyperT3 Dysgerminoma malignant, eq to but rarer than male seminoma; uniform sheets of cells, large nuclei; tumor marker: hCG, LDH Choriocarcinoma can develop in pregnancy in mother or baby; hyperchromatic, large F

d (hematogen. spread) nuclei; increase frequency of theca-lutein cysts; hCG n a

Yolk sac (endodermal in testes, ovaries, or sacrococcygeal area of kids; yellow, friable, solid

M sinus) masses; 50% have Schiller Duval bodies; AFP Ovarian tumors: Non-germ cell (CA-125=general ovarian cancer marker) Serous cystadenoma most common benign ovarian tumor, fallopian-tube epithelium Serous cystadenoca 50% of all ovarian tumors; malignant, frequently bilateral; BRCA-1, HNPCC (FHx is most important risk factor) Mucins cystadenoma mulitlocular cyst, benign, intestine-like tissue Mucins cystadenoca pseudomyxoma peritonei: intraperitoneal mucus accumulation Brenner tumor benign, looks like bladder Fibromas bundles of spindle-shaped fibroblasts, part of Meigs' Sz Granulosa cell tumor secretes E (precocious puberty, endometrial hyperplasia/ca), abnormal uterine bleeding Call-Exner bodies (red, exracellular) Krukenberg tumor GI malignancy that mets to both ovaries, mucin-secreting vaginal sarcoma botryoides (rhabdo variant): <4yo, spindle-shaped, desmin-positive Testicular tumors: Germ cell (95% of testicular tumors, can be mixed, all malignant) Seminoma painless, homogenous test, enlargement; most common test. tumor, 25yo, radiosensitive, late mets; lobules, clear cytoplasm Embryonal ca painful, worse prognosis, often glandular/papillary, can differentiate to other tumors; can have AFP/hCG tumor markers Teratoma mature teratoma is most likely malignant Testicular tumors: Non-germ cell (5%, mostly benign) Leydig cell contains Reinke crystals; gynecomastia, precocious puberty Sertoli cell androblastoma from sex cord stroma Testicular lymphoma common in older men Benign breast tumors Fibroadenoma most common tumor <35yo; small, mobile, firm, sharp edges; responds to estrogen (pregnancy, menstruation); not pre-malig. Intraduct papilloma serous or bloody nipple discharge, slight increased risk for ca Phyllodes tumor most common in 60s; big, leaf-like projections; may transform Malignant breast tumors Invasive ductal most common, worst; firm, fibrous, sharp margins, small cells Invasive lobular orderly rows of cells, often multiple and bilateral Medullary fleshy, cellular, lymphocyte infiltrate, good prognosis Comedocarcinoma ductal, caseous necrosis, DCIS subtype Inflammatory dermal lymphatic invasion by ca and block (Peau d'orange) 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 Lung volumes inspiratory capacity=IRV + TV

FEV1=after full inspiration, V forcibly expired in the first second; low in restrictive, very low in obstructive FVC=after full inspiration, total V forcibly expired; low in obstructive, very low in restrictive

FEV1/FVC=hallmarks: obstructive<70%, restrictive>80%

O2 in the blood Equation Nl value Changed by O2 content BC + dissolved O2 20.4g/mL any change in BC or DO2 binding capacity 1.34 * Hb * % sat 20.1g/mL down: anemia dissolved O2 PO2 * 0.3% 0.3g/mL up: 100% O2

Lung cancer Type Location Characteristics SqCC (smoking) central cavitation, PTHrP; keratin pearls, intercell'ar bridging Small CC central very aggressive; ACTH, ADH, Lambert-Eaton, chemo- responsive, inoperable; NET (Kulchitsky cells=dark) bronchial adenoca periph prior pulmonary injury site; nonsmokers bronchioalveolar periph grows along airways (pneumonia-like), can cause hypertrophic osteoarthropathy Large CC periph highly anaplastic, surgical tx, poor prognosis; giant cells w/ leukocyte fragments in cytoplasm pneumonic "coin" lesion on XR, noncalcified nodule on CT; mets to brain (epilepsy), liver (jaundice, HM), adrenal, bone (break); met from breast, colon, prostate, bladder pneumonic "coin" lesion on XR, noncalcified nodule on CT; mets to brain (epilepsy), liver (jaundice, HM), adrenal, bone (break); met from breast, colon, prostate, bladder complications: SVC Sz, Pancoast (Horner's), paraneoplastic, effusions, hoarseness

ARDS: diffuse alveolar damage, protein-rich leakage into alveoli, forms haline membrane, initial 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 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) Biochem (pathology)

Hemophilia (A and B) Wiskott-Aldrich Bruton's agammaglobulinemia OTC deficiency Hunter's

Leucine, Lysine Methionine, Valine, Arginine, Histidine Phenylalanine, Isoleucine, Threonine, Tryptophan Glutamate, Aspartate Lysine, Arginine (most basic), Histidine (no charge at body pH)

Lipid transport LDL HDL B-100 A-1, A-2 LCAT: lecithin-chlsl acyltransferase, in HDL and LDL, esterifies 2/3 of plasma chlsl CETP: chlslester transfer protein, takes chlsl from HDL to LDL/VLDL, TG back to HDL hyperchylomicronemia (I): LPL def or altered apoC-II (cofactor) causes high TG and chlsl; pancreatitis, HSM, eruptive xanthomas, no increased risk for atherosclerosis familial hyperchlslemia (IIa): AD, absent LDL-R causes increased LDL, chlsl, tendon (Achilles) xanthomas, accelerated atherosclerosis (MI<20yo), corneal arcus hyperTGemia (IV): hepatic VLDL overproduction causes increased TG, pancreatitis abetalipoproteinemia: AR, MTP (microsomal TAG transfer protein, loads apoB with lipids) def causes inabilty to synthesize VLDL/chylo; sx: FTT, ataxia, steatorrhea, malabsorption,

PKU: Phe OHase or THB def, Tyr is essential, screened for 2-3d after birth (normal at birth from maternal enzyme); sx: mental/growth retardation, seizures, musty body odor, fair skin, eczema; maternal PKU: microcephaly, mental/growth retardation, CHD branched/VLCFA cant undergo β-ox, so degraded in peroxisomes (def causes improper CNS

Embryo Fetal landmarks d3=morula; d6=blastocyst implantation, hCG secretion begins laminar disk (epi-/hypo-blast), placenta (syncytio-/cyto-trophoblast) gastrulation/primitive streak; d18=notochord; d21=neural tube closure heartbeat, limb buds form (4 chambers, 4 limbs) embryonic period: organogenesis, most susceptible to teratogens fetal period: movement, looks like baby genitalia have M/F characteristics

Embryologic derivatives epidermis, adenohypophysis, lens, salivary/sweat/mammilary glands, oral/olfactory epithelium, sensory organs of inner ear CNS (brain, neurohypophysis, oligodendrocytes, astrocytes, ependymal cells,

PNS (incl. chromaffin cells of adrenal medulla), AP septum, pia, arachnoid, skull bones, odontoblasts, C-cells of thyroid, melanocytes sophageal fistula, Renal, Limb; bone, mm, connective tissue/dura, spleen, GU, Eustachian tube 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 Bacteria S. aureus Capsule, esp S. pneumo, H. flu, N. meningitides Pseudomonas aeruginosa C. perfringes (gas gangrene) S. aureus Pasteurella multocida Klebsiella Trophyerma whippelii S. agalactiae (group B) HBV (needle stick) Mucor/Rhizopus catalase (+): S. aureus, Nocardia, Aspergillus Candida (systemic), Aspergillus Borrelia burgorferi (Ixodes, so is Erlichia & Babesia) syphilis H. flu Actinomyces israelii

Parasites mebendazole albendazole raw fish raw fish inflamed spleen/ liver, granulomas from bacterial infxn hookworms nematode raw pork microfilaria allergy Protozoa steatorrhea/STD dysentery amastigotes too

Pneumonia elderly S. pneumo viruses (flu) anaerobes H. flu GNR

Meningitis elderly S. pneumo GNR L. monocytogenes meningism (nuchal rigidity, photophobia, headache), Kernig's sign (flex hip, rigidity on knee extension), Brudzinski's sign (prone, head lifted, feet lift involuntarily) Immune HLA/disease associations DM type I RA, DM type I pernicious anemia, Hashimoto's steroid-responisve nephrotic sz

(Mnemonic: "Hot D8, My GoodnEss, A Hot/Cute Lynn Comes") pyrogen, induces endothelial adhesion molecules/chemokines activates CD8 (signal 2) hematopoietic cells to become myeloid precursors differentiation to Th2, and class switching to IgG and IgE differentiation of BC, class switch to IgA, eosinophil maturation pyrogen, induces acute phase reactants hematopoietic cells to become lymphoid precursors chemotactic acts on hematopoietic cells, anti-apoptotic, pro-growth activates Th2, inhibits activated TC and Th1 hematopoietic cells to become megakaryocytes, bone prolif differentiation to Th1, activates NK mediates septic shock, activates endothelium, leaky activates macrophages and Th1, inhibits Th2, ups MHC1 and 2

AutoAbs and associated disorder dz DM type 1 Celiac CREST Hashimoto's PBC pemphigus vulgaris Wegener's

Path β-sheet, Congo red stain, apple green birefringence, gross=waxy from Ig light chains (multiple myeloma, BJ proteins) serum amyloid-ass'd protein (chronic inflammation) from transthyretin from amylin from calcitonin from amyloid precursor protein from MHC I proteins

Tumor suppressors: two mutations needed tumors (gene product) retinoblastoma, osteosarcoma most cancers, Li-Fraumeni Sz q) breast and ovarian cancer q) breast ca (DNA repair protein) melanoma colorectal cancer (assn w/ FAP) Wilms' tumor NFM type 1 NFM type 2 pancreatic cancer colon cancer

GP-linked 2nd messengers vascular smooth m contraction (1B), sphincter m contraction, mydriasis decrease sympathetic outflow and insulin release increases HR, contractility, lipolysis, renin release vaso-/broncho-dilation, drops uterine tone in CNS, postsynaptic autonomic ganglia, gastric (ECL)/salivary secretion decrease HR and contractility of atria gut peristalsis, bladder contraction, eye (miosis, accomodation), bronchoconstriction, increased exocrine secretion (DUMBLS) relaxes renal vascular smooth m, brain esp in brain, modulates transmitter release increased mucous production, bronchiole contraction, pruritis, pain increased gastric acid secretion increased vascular smooth m contraction increased water reuptake in collecting tubules of kidney

Murmurs Cause RF (MR and TR), MVP, ischemia, LV dilation dilation, endocarditis myxomatous degen, RF, chordae rupture age calcifications, bicuspid aortic valve RF (vast majority) root dilation, RF, bicuspid valve

rubella, prematurity

Angina/MI

V3 | V4 V5 | V6 + | + | + | | | + | + | + | + | | | |

MI markers most specific (also PE, myocarditis), rises after 4h, peak 12h, stays 7-10d non-specific, good for reinfarction on top of acute MI, gone by 3d least specific, peaks at 2d, stays for a while Evolution Gross Risk dark, mottled, pale w arrhythmia tetrazolium dye hyperemic arrhythmia or rupture (day 4) hyperemic border, rupture centrally yellow-brown (wall, chordae) grey white aneurysm

Endocrine Signalling pathways of hormones Ca (PTH, calcitonin), ADH (V2R)/α-subunits (FSH, LH, TSH, β-hCG), melanotropic

α-subunitRH (GnRH, TRH), posterior pit (oxytocin, ADH) all steroids but T3/4: DHT, P, E2, D3, cortisol, aldo -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 GH, PRL, IL's, CSF

DM dx 2h glucose tolerance <140 140-200 >200 or sx of hyperglycemia and a casual (random) plasma glucose >200

(all have enlarged adrenal glands due to low cortisol and thus high ACTH) Other hypovolemic shock in newborn masculinization, as w 21-OHase M=pseudoherm, F=sexual infant

Multiple endocrine neoplasias (MEN) ), pituitary (usually PRL or GH), and stomach ulcers) medullary thyroid cancer, pheo, parathyroid (kidney stones) medullary thyroid cancer, pheo, oral or intestinal ganglioneuromatosis

MEN 2A and MEN 2B associated w/ ret gene (oncogene, tyrosine kinase)

T3/T4: synthesized by peroxidase from I + tyrosine (inhibited by anions and PTU or methimazole); bone growth, CNS maturation, increased β1 in heart, increased metabolic rate;

: hot nodule, mutated TSH-R, rarely : presents during stress, type II hypersensitivity; thyrotoxicosis: complication of hyperT3, stress-induced catecholamine surge, death by arrhythmia; Jod- myxedema (facial/periorbital), severe=myxedema coma (hypothermia and altered Hashimoto's: thyroiditis, so may be hyperT3 early, autoimmune (antimicrosomal antithyroglobulin Ab, HLA-DR5), Hurthle cells, : severe fetal hypoT3, co-endemic with goiter, pot-bellied, pale, puffy faced, protruding umbilicus, protuberant tongue; subacute (de Quervain's): self-limited, following flu-like illness, jaw pain, early inflammation : replaced by fibrous tissue, rock-hard : most common, excellent prognosis, "Orphan Annie" nuclei (ground : uniform follicles, good prognosis; : from C cells, sheets in amyloid stroma, assn w/ MEN2A/B; : assn w/ Hashimoto's low T4 to T3: PTU, glucocorticoids, amiodarone, iopanoate, non-selective β-blockers

GI GI hormones/secretions Other ectopic production= Zollinger-Ellison Sz; AAs: Phe and Try are potent stimulators

incretin

acts on neural muscarinic pathways to stimulate the panc anti-GH effects

VIPoma: panc tumor, copious diarrhea agonists useful autoimmune attack= chronic gastritis/PA

pepsinogen to pepsin by H+ bicarb is trapped in mucous that covers gastric epithelium IBD UC (autoimmune) continuous, always involves rectum friable mucosal pseudopolyps, loss of haustra sub-/mucosal inflammation only, crypt abscesses/ulcers malnutrition, toxic megacolon, colorectal carcinoma (hi risk) bloody diarrhea, PSC, pyoderma gangrenosum, ankylosing spondylitis, uveitis ASA, 6-MP, infliximab, colectomy drugs causing GI path: macrolides=acute cholestatic hepatitis; INH=hepatitis; hepatic mushroom poisoning GI pathology Use hepatocyte damage (virus: ALT>AST; alcohol: AST>ALT), MI (AST)

post-HC (obstructive) high highest low heme to unconjugated bilirubin in macrophage, albumin carries (complex=indirect bilirubin) to liver, conjugated by UDP glucuronyl transferase to direct bilirubin, into biliary lumen by

: autodigestion; obstruction (gallstones, ERCP), overworked (EtOH, hypercalcemia, hyperTGemia), mumps, trauma, autoimmune, drugs (sulfa, steroids); sx: epigastric abd pain radiating to back, anorexia, N, elevated lipase (more specific) and amylase; can cause DIC, ARDS, diffuse fat necrosis, hypoCa, pseudocyst, infxn, hemorrhage, : can cause pancreatic insufficiency (ADEK deficiency, steatorrhea, pancreatic adenoca: CEA and CA-19-9 markers, NOT assoc'd w/ EtOH; sx: abd pain radiates to back, weight loss, Trousseau's, jaundice, palpable GB (Courvoisier's sign) acute calculus cholecystitis: obstruction, chemical irritation, mucous disruption, bile acid attack on mucosa, PG release, hypomotility, distension, ischemia, bacteria

Heme/Onc

: low haptoglobin, Hb in urine, not usually jaundiced trigger: fava beans, infxn, INH, sulfa, anti-malarial, aspirin, ibuprofen, nitrofurantoin; back pain, Heinz bodies, and bite cells glycophosphatidyl inositol links decay accelerating factor onto RBC membrane, prevents complement cascade; high urine hemosiderin schistocytes; micro-: from DIC, HUS (Shiga toxin), SLE, malignant htn; macro: malaria, Babesia : cleared in spleen; high unconjugated bilirubin, jaundice; (Wilsons) glu to val on β gene; marrow expansion, aplastic crisis (B19), bone crises, renal papillary necrosis/microhematuria, splenic sequestration crisis, autosplenectomy glu to lys, compound heterozygotes w/ HbSC have milder dz than HbSS hereditary def in cytoskeletal elements (ankyrin, band 3.1, spectrin); high MCHC, high RDW, SM, aplastic crises; tx=splenectomy (Howell-Jolly body) AR, pyruvate kinase def, low ATP, rigid RBC membrane; HA in newborn spherocyte; warm=IgG: SLE, CLL, α-methyldopa; cold=IgM: CLL, mono, M. pneumo; hydrops fetalis; usually Coomb's positive (direct=anti-IgG Ab)

Hemoglobin types When present normally 95% of Hb non-enzymatic glycation of normal Hb, <6%, higher in DM normally 3% of Hb, higher in beta-thal minor beta variant, mild hemolytic anemia beta variant, mild hemolytic anemia normal in fetal, higher in sickle cell alpha-thal beta variant, sickle cell early embryonic stage late embryonic stage

% transferrin sat (serum Fe/TIBC) low nl high low high Pb poisoning: microcytic/sideroblastic anemia, basophilic stippling of RBCs, renal, GI dz; kids: neuro deterioration, wrist/foot drop, Pb lines on gums/long bones (XR), abd pain; adults

Translocations Mantle Ewing's t(11;14) t(11;22) - -

associated dzs

lung dz, CHD, altitude ectopic erythropoietin

Musculoskeletal Upper extremity nerve lesions Injury humerus dislocation, surgical neck break upper trunk hum. midshaft break, Saturday night palsy carpal tunnel, lunate dislocation supracondylar humerus fracture fracture of the hook of the hamate medial epicondyle of humerus, funny bone lower trunk (birth) Lower extremity nerve lesions Injury ant. hip dislocation pelvic fracture fibular neck fracture, lateral leg trauma knee trauma

post. hip dislocation + polio

Bone tumors Description benign bone tumor; mature bone w/ cartilage cap; from metaphyses; transformation rare intramedullary bone, usually distal extremities trabeculae of woven bone surrounded by osteoblasts (lytic), <2cm, usually proximal tibia/femur trabeculae of woven bone surrounded by osteoblasts, epiphyseal plates of long bones (esp knee); locally aggressive; XR='soap bubbles'; spindle-shaped cells new piece of bone growing on another, often in skull Description 2nd most common 1° malignancy (MM); XR=Codmans triangle or sunburst pattern, from metaphyses (esp knee); risk: Paget's, bone infarcts, radiation, Rb extremely aggressive, early mets, chemo-responsive; XR=onion-skin; anaplastic small blue cells, t(11;22) may be from osteochondroma; intramedullary

Arachidonic acid products keeps PDA open; misoprostol=agonist up: pain, uterine tone, temperature; down: vascular tone "prostacycline", down: platelet aggregation, vascular tone, uterine tone up: platelet aggregation, vascular tone neutrophil chemotaxis up: smooth m tone, vascular tone/permeability, bronchial tone (-lukast=I)

Infectious derm S. aureus, S. pyogenes S. aureus, S. pyogenes S. pyogenes or anaerobes

SJS-TEN: anti-psychotic/anti-epilepsy (ethosuxamide, lamotrigine, carbamazepine, phenobarbital, phenytoin), abx (sulfa, PCN), anti-gout (allopurinol), analgesics (NSAIDs), NNRTIs (efavirens, nevirapine); Nikolski's sign, mucosal involvement Neuro

2nd Order/Synapse/3rd Order 2=decussates in medulla, ascends contralaterally in medial lemniscus; S=VPL of thalamus; 3=sensory cortex

2=decussates at anterior white commisure, ascends contralaterally; S=VPL of thalamus; 3=sensory cortex first synapse=cell body of anterior horn (spinal cord); LMN: leaves spine, to NMJ (synapse 2)

2=ascend on internal carotid; S=sup. cervical ganglion; 3=int. carotid to long ciliary n (V1)

Hemorrhages will cross falx, tentorium, not suture lines, rapid expansion bridging v rupture, elderly/shaken baby, crescent-shaped worst headache of life, ruptured aneurysm, yellow/red spinal tap, vasospasm 2-3d later (blood breakdown products, tx=CCB)

Spinal cord lesions mucosa to blood to CNS, destroys anterior horn; nonspecific sx going to LMN signs; virus recovered from stool or throat AR, degeneration of anterior horns, floppy baby, young death anterior white commissure lesion, usually C8-T1; assn w Chiari 3° syphilis, dorsal root and column degen; locomotor/sensory ataxia, Charcot joint, shooting pain, no DTRs, positive Romberg demyelination of lateral corticospinal, spinocerebellar, and doral columns; ataxic gait, hyperreflexia, impaired vib/position staggering, frequent falls, nystagmus, dysarthria, pes cavus, hammer toes, HCM (cause of death), childhood kyphoscoliosis spares dorsal columns and posterolateral tract (of Lissauer); upper thoracic ASA is watershed (a of Ademkiewicz below T8) both UMN and LMN signs, no sensory, cognitive, or oculomotor defects, can be from superoxide dismutase 1; tx=Riluzole autoimmune inflammation and demyelination of CNS, white F, 20-30; scanning speech, intention tremor, MLF sz (internuclear ophthalmolegia), incontinence, nystagmus, optic neuritis, relapsing/remitting; MRI for dx, high IgG in CSF (oligoclonal bands=dxtic), periventricular plaques (oligodendrocyte loss, reactive gliosis, axon preservation) 50% are mets; presentation due to mass effect (seizure, dementia, etc) supratentorial, benign, confused w/ pit adenoma, calcifications well circumscribed, low grade, cystic + solid, GFAP [+], may be supratentorial; Rosenthal fibers: eosinophilic corkscrews malignant, primitive neuroectoderm, can compress 4th ventricle (hydrocephalus); pseudorosettes or rosettes, small blue cells poor prognosis, usually 4th ventricle (hydrocephalus); blepharoplasts (rods, basal ciliary bodies), pseudorosettes can produce EPO, ass'd w/ vHL; foamy cells, highly vascular most common 1°, cerebral hemispheres, can cross corpus, GFAP [+]; pleomorphic, pseudopalisading, around areas of necrosis from arachnoid cells, whorled spindle cells, psammoma bodies commonly on VIII (esp NFM), resectable, S-100 [+] rare, slow growing, frontal lobe; chicken-wire capillary pattern surrounding fried egg cells, can be calcified usually PRL, hyper/hypo-pit, bitemporal hemianopia oligodendrocyte destruction, assc'd w/ JC virus, 2-4% of AIDS, rapidly fatal AR lysosomal storage dz, arylsulfatase A def, buildup of sulfatides, perivenular inflammation and demyelination, after infxn (VZV, measles) or vax (rabies, smallpox)

peripheral: more common, positional testing=delayed horizontal nystagmus; central: brain stem/cerebellum, testing=immediate nystagmus, any direction

Ego defenses manifestation as physical sx (grief causes "blindness", hysteria) denial, delusional/extreme projection, distortion, splitting (all good/all bad) impulses attributed to external source remaining partially at a more childish level acting out, fantasy, idealization, identification (modeling after power, not admiration) feelings transferred to safer outlet, scapegoating going back to childish level dissociation, rationalization (excuses), isolation of affect, repression, rxn formation withholding from conscious awareness unacceptable impulses in an acceptable way (aggression/boxer) humor, altruism

: odd/eccentric, no meaningful relationships; assc'd w/ schizophrenia voluntary social withdrawal, limited emotional expression + eccentric beliefs/appearance, magical thinking, awkward : dramatic, emotional; associated w/ mood disorders and substance abuse disregard for rights of others, criminal, M>F >18, (conduct dzd) unstable, impulsive, self-mutilating, emptiness, F>M; splitting excessively emotional, attention seeking, overly sexual grandiose, sense of entitlement, lacks empathy hypersensitivity to rejection, inhibited, desires relationships perfectionist, ego syntonic (OCD=dystonic, ass'd w Tourette's) submissive, clingy, low self confidence

Psych txs BDZ methylphenidate, amphetamines (dexedrine) antipsychotics antipsychotics (esp haloperidol) SSRIs, SNRIs, TCAs MAOIs, SSRIs Mirtazapine stabilizers (valproate, Li, carbamazepine), atypicals SSRIs BDZ, buspirone, SSRIs SSRIs, TCAs, BDZs SSRIs SSRIs

Behavioral Science Early developmental milestones orients to voice social smile stranger anxiety separation anxiety, few words object permanence, 200 words gender identity, parallel play 900 words, complete sentences cooperative play, imaginary friends, grooms self, buttons and zips 1=childhood; 2=adrenarche (pubic hair, breasts); 3=hair darkens, curls, penis longer; 4=penis wider, scrotum darkens, raised areolae; 5=adult, areolae not raised circadian rhythm driven by suprachiasmatic nuc of hypothalamus, regulated by light

Renal Electrolyte disturbances High irritability, delirium, coma EKG changes (peaked T's, wide QRS), delerium, renal stones, abd pain, stupor delerium, low DTRs, cardiopulm arrest renal stones, metastatic calcifications lost heparin sulfate causes massive proteinuria (>3.5g/d, thromboemboli, FSGS: most common GN in : aka lipoid nephrosis, in kids, triggered by recent infxn, : (type III) drugs, infxn, SLE, tumors, thickened : can be nephritic too, type 1="tram track" (HBV/HCV related), type 2=dense deposits (EM, assc'd w/ C3 nephritic factor); diabetic : non-enzymatic glycosylation (NEG) of GBM causes thickening and increased permeability, NEG of efferent increases GFR causing mesangial expansion, nodular

inflammation of glomeruli causes (PHAROH) proteinuria (<3.5g), hematuria, (Berger's dz): increased IgA synth, often presents after URI or acute gastroenteritis, assc'd w/ Henoch-Schonlein; acute poststrep : in kids, glomeruli enlarged/hypercellular, "lumpy-bumpy", periorbital/peripheral rapidly progressive (crescent) GN: crescents of fibrin, plasma proteins, parietal cells, monocytes, & macrophages, poor prognosis, from Goodpastures, diffuse proliferative: from SLE or

Immune deposits Mesangial Berger's Dz (IgA nephropathy)

Immunofluorescence Pattern Light and Dark Areas Berger's Dz (IgA nephropathy)

Other Characteristics Low Complement Postinfectious GN MPGN Cryoglobulinemia

Kidney stones CaOx most common, can be from ethylene glycol or vit C abuse; hyperPTH infxn w/ urease bugs (Proteus, eg), can be staghorn, worse w/ alkaluria , strong assn w/ hyperuricemia (gout, B3), high cell turnover , usually 2° to cystinuria, tx=alkalinize urine ARF (acute kidney injury) Epidemiology community hospital BPH/cancer mets 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 Placental pregnancy complications 3rd trimester, painful bleeding; premature detachment of placenta; fetal death, any trimester, painless bleeding; placental attachment to lower uterine segment, after delivery, massive bleed; defective decidua (placental attachment to myometrium), no separation; risk: prior C-section, placenta previa after delivery, may cause hemorrhage endometriosis: ectopic endometrial glands, nonneoplastic, cyclic bleeding/pain or chocolate cysts, usually in ovary/peritoneum; adenomyosis: w/i myometrium endometrial hyperplasia (excess E, sx=postmenopausal bleeding; risk=anovulatory cycles, HRT, PCOS, granulosa cell tumor) biggest risk for endometrial carcinoma endometrial carcinoma: most common gynecologic malignancy; sx=vaginal bleeding; risk=obesity, DM, htn, nulliparity, late menopause, PCOS, endometrial hyperplasia leiomyoma=fibroid, most common tumor in F, usually multiple, well- demarcated, benign, E-sensitive (grows w/ pregnancy), 30yo; asxatic, abnormal uterine bleeding, Fe def anemia, miscarriage; whorled pattern of smooth mm bundles; leiomyosarcoma: irregular shape, necrosis, recur, aggressive, usually middle-aged PCOS, obesity, HPO abnormalities, POF (menopause before 40, follicular atresia),

PCOS: high LH causes anovulation, hyperandrogenism (androstenedione from theca cells); low FSH, high T, enlarged bilateral cystic ovaries, amenorrhea, hirsutism, and obesity; assn w

follicular cyst=unruptured Graffian follicle; corpus luteum cyst=hemorrhage into persistent CL, regresses spontaneously; theca-lutein cyst=bilateral/multiple, from Gn stimulation, assn w chorioca and moles; chocolate cysts=endometriosis

90% of ovarian germ cell tumors; cells from 2-3 germ layers; mature=benign, immature=aggressive; struma ovarii=hyperT3 malignant, eq to but rarer than male seminoma; uniform sheets of cells, large nuclei; tumor marker: hCG, LDH can develop in pregnancy in mother or baby; hyperchromatic, large nuclei; increase frequency of theca-lutein cysts; hCG in testes, ovaries, or sacrococcygeal area of kids; yellow, friable, solid masses; 50% have Schiller Duval bodies; AFP (CA-125=general ovarian cancer marker) most common benign ovarian tumor, fallopian-tube epithelium 50% of all ovarian tumors; malignant, frequently bilateral; BRCA-1, HNPCC (FHx is most important risk factor) mulitlocular cyst, benign, intestine-like tissue pseudomyxoma peritonei: intraperitoneal mucus accumulation benign, looks like bladder bundles of spindle-shaped fibroblasts, part of Meigs' Sz secretes E (precocious puberty, endometrial hyperplasia/ca), abnormal uterine bleeding Call-Exner bodies (red, exracellular) GI malignancy that mets to both ovaries, mucin-secreting vaginal sarcoma botryoides (rhabdo variant): <4yo, spindle-shaped, desmin-positive (95% of testicular tumors, can be mixed, all malignant) painless, homogenous test, enlargement; most common test. tumor, 25yo, radiosensitive, late mets; lobules, clear cytoplasm painful, worse prognosis, often glandular/papillary, can differentiate to other tumors; can have AFP/hCG tumor markers mature teratoma is most likely malignant contains Reinke crystals; gynecomastia, precocious puberty androblastoma from sex cord stroma common in older men Benign breast tumors most common tumor <35yo; small, mobile, firm, sharp edges; responds to estrogen (pregnancy, menstruation); not pre-malig. serous or bloody nipple discharge, slight increased risk for ca most common in 60s; big, leaf-like projections; may transform Malignant breast tumors most common, worst; firm, fibrous, sharp margins, small cells orderly rows of cells, often multiple and bilateral fleshy, cellular, lymphocyte infiltrate, good prognosis ductal, caseous necrosis, DCIS subtype dermal lymphatic invasion by ca and block (Peau d'orange) 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 Lung volumes

Changed by any change in BC or DO2 down: anemia up: 100% O2

Lung cancer Characteristics cavitation, PTHrP; keratin pearls, intercell'ar bridging very aggressive; ACTH, ADH, Lambert-Eaton, chemo- responsive, inoperable; NET (Kulchitsky cells=dark) prior pulmonary injury site; nonsmokers Clara cell, grows along airways (pneumonia-like), multiple can cause hypertrophic osteoarthropathy densities highly anaplastic, surgical tx, poor prognosis; giant cells w/ leukocyte fragments in cytoplasm pneumonic "coin" lesion on XR, noncalcified nodule on CT; mets to brain (epilepsy), liver (jaundice, HM), adrenal, bone (break); met from breast, colon, prostate, bladder complications: SVC Sz, Pancoast (Horner's), paraneoplastic, effusions, hoarseness

ARDS: diffuse alveolar damage, protein-rich leakage into alveoli, forms haline membrane, initial 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 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 Addison's Dz Albright's hereditary osteodystrophy Alport's Sz Alzheimer's Dz

Andersen's Dz Angelman's Sz Becker's MD Berger's Dz Boerhaave Sz Broca's aphasia Budd-Chiari Sz

Buerger's Sz

Caplan's Sz Chagas' Dz Charcot-Bouchard Sz Charcot-Marie-Tooth Sz Chediak-Higashi Sz

Cheyne Stokes breaths Chiari malformation

Churg-Strauss Sz

Conn's Sz Cori's Dz Creutzfeldt-Jakob Dz Cri-du-chat Sz Crigler-Najjar Sz, type 1 Crigler-Najjar Sz, type 2 Curling's ulcer Cushing's ulcer Dandy-Walker Sz DiGeorge Sz

Dressler's Sz Dubin-Johnson Sz Duchenne's MD

Edwards' Sz Ehlers-Danlos Sz

Eisenmenger's Sz Endemic Typhus Epidemic Typhus Fabry's Dz

Fanconi's anemia Fanconi's Sz Fitz-Hugh-Curtis Sz

Friedrich's ataxia

Gardner's Sz Gaucher's Dz

Gerstmann Sz Gilbert Sz Glanzmann's thrombasthenia Guillan-Barre Sz

Hartnup Dz Henoch-Schonlein purpura

Hirschsprung Dz Hunter's Sz Huntington's Dz Hurler's Sz

I-cell (inclusion) dz Jarisch-Herxheimer rxn Jervell and Lange-Nielsen Job'sSz Sz

Kallmann Sz Kartagener's Sz Kawasaki's Dz

Kluver-Bucy Sz Krabbe's Dz

Krukenberg's tumor Lambert-Eaton Sz

Lesch-Nyhan Sz

Leser-Trelat Sign Lewy Body dementia Libman Sachs Li-Fraumeni Sz Loffler's Sz Lynch Sz Mallory-Weiss Sz Marfan's Sz

McArdle's Dz McCune-Albright Sz

Meigs' Sz Menetrier's Dz Meniere's Dz Myasthenia Gravis Neimann-Pick Dz

Osler-Weber-Rendu Sz Paget's Dz

Parinaud Sz Parkinson's Dz

Patau's Sz

Peutz-Jeghers Sz Pick's Dz

Plummer-Vinson Sz Pompe's Dz Potter's Sz

Pott's Dz Prader-Willi Sz Reiter's Sz Reye's Sz

Riedel's thyroiditis Rotor's Sz Samter's triad Sezary Sz Sheehan Sz Shwartzman rxn Sturge-Weber Dz

Takayasu's arteritis

Tay-Sach's Dz

Temporal arteritis

Treacher-Collins Sz Trousseau's Sz Turcot's Sz Typhoid fever von Gierke's Dz von Hippel-Lindau Dz

Waldenstrom's macroglobulinemia Wallenberg's Sz

Waterhouse-Friderichsen Sz Wegener's granulomatosis

Weil's Dz Wenckebach Werdnig-Hoffman Sz Wernicke-Korsakoff Sz Wernicke-Korsakof Sz Wernicke's aphasia Whipple's Dz William's Sz Wilson's Dz

Wiskott-Aldrich Sz Wolff-Parkinson-White Sx hypotn, hyperkalemia, acidosis, skin hyperpigmentation hypocalcemia, tetany, shortened 4th/5th digits, short stature progressive heridetary nephritis, deafness, and cataracts dementia, can get intracranial hemorrhage, cortical atrophy, intracellular neurofibrillary tangles (hyperphosphorylated tau) cirrhosis and death w/i 5y retardation, seizures, ataxia, inappropriate laughter mm weakness, presents in early adulthood nephritic sz (PHAROH), mesangial immune deposits transmural esophageal rupture nonfluent, intact comprehension congestive liver disease: HSM, ascites, abd pain, liver failure, varices, NO JVD intermittent claudication, severe pain, superficial nodular phlebitis, Raynaud's, can cause gangrene and autoamputation cough, SOB, joint inflammation (RA) dilated CM, megacolon, megaesophagus microaneurysms in small vessels (basal ganglia, thalamus) aka hereditary motor and sensory neuropathy (HMSN) recurrent pyogenic infxn, partial albinism, peripheral neuropathy, large lysosomal vescicles in phagocytes oscillating slow/fast breathing II: assn w/ aqueductal stenosis, hydrocephaly, syringomyelia, lumbar meningomyelocele usually asthma, sinusitis, skin lesions, peripheral neurophathy (wrist/foot drop); can also hit heart, GI, kidneys htn, hypokalemia, MAlk mild form of von Gierke's (gluconeogenesis intact), no LAc rapidly progressive dementia with myoclonus microcephaly, retardation, epicantal folds, cardiac problems early death, jaundice, kernicterus, high indirect bilirubin high indirect bilirubin, can be treated with phenobarbital acute gastritis and ulcer acute gastritis and ulcer assn w/ hydrocephalus, spina bifida, posterior fossa enlargement parathyroid/thymic aplasia (hypoCa/TC def), cardiac defects (TOF, truncus arteriosus) low grade fever, pleuritic chest pain, pericarditis (self-limited) conjugated hyperbilirubinemia, grossly black liver, benign mm weakness, begins in pelvig girdle, progresses superiorly, pseudohypertrophy of calf/delt, DCM, Gowers' maneuver (use of arms to stand), presents <5yo, high CPK microcephaly, rocker-bottom feet, clenched hands, heart defect hyperextensible skin, bleeding tendency/aneurysms/organ rupture, hypermobile joints/dislocations PAH, late cyanosis, clubbing, polycythemia rash starts centrally and spreads outward, fever, headache rash starts centrally and spreads outward, fever, headache peripheral neuropathy (esp hands and feet), angiokeratomas, cardiovascular and renal diseases aplastic anemia, short stature, tumors/AML (high risk) polyuria, acidosis, growth failure, electrolyte imbalances acute RUQ pain, referred to R shoulder, "violin string" appearance staggering gait, frequent falls, nystagmus, dysarthria, pes cavus, hammer toes, HCM (cause of death), presents as childhood kyphoscoliosis

CRC, osteomas, and soft tissue tumors, retinal hyperplasia HSM, osteoporosis, aseptic necrosis of femur/bone crises, mental retard., Gaucher's cells (macrophages look like crumpled paper) acalculia, agraphia, finger agnosia, L/R disorientation benign mild jaundice with stress/fasting increased bleeding time, normal platelet count, smear shows no clumping symmetric,rapidly-ascending mm weakness, begins in distal LE, facial paralysis in 50%, papilledema, autonomic dysfunction not uncommon (htn, eg); usually resolves wks-mos pellagra (diarrhea, dermatitis, dementia) from low tryptophan skin rash (palpable purpura) on buttocks and legs, arthralgias, intestinal hemorrhage, abdominal pain, melena congenital megacolon, constipation, failure to pass meconium mild Hurler's, no corneal clouding, aggressive behavior chorea, athetosis (writhing fingers), dementia, aggression, depression developmental(mistaken for substance delay, gargoylism, abuse sometimes) airway obstruction, corneal clouding, HSM coarse facial features, clouded corneas, restricted joint movement, high fever,plasma chills, levels headache, of lysosomal myalgia proteins after syphilis tx long QT, sensorineural hearing loss coarse facies, "cold" abscesses, retained primary teeth, hyper-IgE, derm problems (eczema), recurrent colds lack of 2° sex characteristics (hypogonadotropic), anosmia infertility, bronchiectasis, recurrent sinusitis, situs inversus fever, conjunctivitis, strawberry tongue, lymphadenitis, desquam-ative skin rash, can develop coronary aneurisms (esp if untxed) hyperorality, hypersexuality, disinhibited behavior galactocerebrosidase def causes galactocerebroside accumulation abundant mucous, signet ring cells difficulty climbing stairs, rising from chair, eye sx come later (as opposed to MG where they are early), no reversal w/ AChEIs retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis sudden appearance of multiple seborrheic keratoses Parkinsonism w/ dementia and hallucinations sterile endocarditis, usually benign sarcomas at a young age, many cancers while young

80% progress to CRC, proximal colon always involved hematemesis tall, long extremities, pectus excavatum, hyperextensive joints, arachnodactyly, aortic regurg/dissecting aortic aneurysms (cystic medial necrosis of aorta), MVP, superotemporal lens subluxation cramps, myoglobinuria w/ exercise multiple unilateral bone lesions and café-au-lait spots, endocrine abnormalities (PRL/GHoma, precocious puberty, hyperthyroid) ovarian cysts ovarian fibroma, ascites, pleural effusion (usually R sided transudate), pulling sensation in groin cerebriform rugae, edema, wt loss, precancerous vertigo (relapsing/remitting), hearing loss, tinnitus dyplopia, ptosis, reversal w/ AChEI progressive neurodegeneration, developmental delay, cherry red macula, foam cells, HSM telangiectasias, recurrent epistaxis, skin discolorations, AVMs increased hat size, CN impingement, chalk-stick fractures, high output cardiac failure (increased AV shunts), mosaic patterning paralysis of conjugate vertical gaze pill-rolling tremor (at rest), cogwheel rigidity, brady-/a-kinesia, postural instability, Lewy bodies (intracellular α-synuclein) microcephaly, rocker-bottom feet, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart dz GI hamartomas (polyps), hyperpigmentation of mouth/feet/hands dementia, aphasia, Parkinsonian, change in personality, Pick bodies (hyperphosphorylated intracellular tau) anemia, atrophic glossitis, dysphagia (esophageal webs) cardiomegaly/restrictive CM, exercise intolerance, neuro sx limb/facial deformities, pulmonary hypoplasia, oligohydramnios vertebral narrowing/collapse, spinal mass, back pain retardation, hyperphagia, obesity, hypogonadism, hypotonia conjunctivitis/anterior uveitis, urethritis, arthritis (large joint) mitochondrial abnormalities, microvescicular fatty liver, hypoglycemia, coma, hepatoencephalopathy rock-hard, non-tender goiter, hypothyroidism very mild conjugated hyperbilirubinemia asthma attack, hypersensitivity, nasal polyps cutaneous patches and nodules, indolent CD4+ TC lymphoma (postpartum) no lactation, absent menstruation, cold intolerance vasculitis from exposure to endotoxin causing glomerular thrombi facial port-wine stain (nevus flammeus), pheo, ipsilateral lepto- meningioma (intracerebral AVM), seizures, early-onset glaucoma fever, night sweats, high ESR, myalgias, arthritis, ocular disturbances, weak pulses in upper extremities progressive neurodegeneration, developmental delay, cherry red macula, lysosomes w/ onion skin, no HSM unilateral headache, jaw claudication, impaired vision (occlusion of ophthalmic artery), high ESR mandibular hypoplasia, facial abnormalities, hearing loss migratory thrombophlebitis colon and malignant CNS tumors fever, diarrhea, headache, rose spots on abdomen severe fasting hypoglycemia, increased glycogen in liver, hepatomegaly, lactic acidosis, gout hemangioblastomas of retina/cerebellum/medulla, bilateral RCC, pheo, etc

M spike on electrophoresis, hyperIgM, hyperviscosity sx, no lytic bone lesions (like in multiple myeloma) contralateral pain/T loss, ipsilateral dysphagia, hoarseness, no gag reflex, vertigo/diplopia, ipsilateral Horner's, ipsilateral face sensation loss, ipsilateral ataxia organ failure, coma, death, hypotn, shock, DIC, no meningitis cough, dyspnea, hemoptysis, hematuria/red cell casts, chronic sinusitis, otitis media, mastoiditis jaundice, azotemia, hemorrhage, anemia, fever, photophobia usually asxatic floppy baby at birth, tongue fasciculations, death by 7mo confusion, ophthalmoplegia, ataxia anterograde amnesia, confabulation, personality changes fluent, impaired comprehension arthralgias, cardiac and neuro involvement elfin facies, retardation, hyperCa, overly friendly, CV problems Kayser-Fleischer rings, hemolytic anemia, cirrhosis, asterixis, HCC, basal ganglia degeneration, dementia, dyskinesia, dysarthria thrombocytopenic purpura, infxns, eczema; high IgE/A, low IgM ventricles partially depolarize earlier, delta-wave on ECG Pathophys chronic primary adrenal insufficiency (atrophy or destruction) AD bilateral renal unresponsiveness to PTH abnormal type IV collagen APP degradation by β-/γ-secretase yields N-APP (DR6L) or Aβ40/42 (cell death signal or aggregate into plaques), decreased ACh branching enzyme def, glycogen pptation deletion of maternal chromosome 15 XLR mutated dystrophin gene presents/flares w/ URI or acute gastroenteritis, assn w Henoch Schonlein violent retching (alcoholics, bulemics) inferior frontal gyrus occlusion of IVC or hepatic veins causes centrilobular congestion and necrosis; assn w polycythemia, HCC, pregnancy, hypercoaguable state medium-sized vessels, idiopathic segmental thrombosing vasculitis; seen in heavy smokers pneumoconiosis + rheumatoid arthritis Trypanosoma cruzi (protist), from reduviid bug associated w chronic htn defective protein production, presents in childhood microtubule polymerization defect causes decreased phagocytosis central apnea in CHF or high ICP cerebellar tonsil herniation; I: asxatic; II: large vermian displacement p-ANCA, granulomatous vasculitis w/ eosinophilia aldosterone secreting tumor, can be bilateral debranching enzyme (α-1,6-glucosidase) def prions cause α-helix to β-sheet transformation congenital microdeletion of 5p absent UDPGT causes large increase in unconjugated bilirubin low UDPGT causes large increase in unconjugated bilirubin burns cause low plasma volume, causing sloughing of the gastric mucosa brain injury causes increased vagal stimulation, increasing H+ production absence of cerebellar vermis, large fourth ventricle 22q11 microdeletion causes aberrant development of 3rd and 4th branchial pouches autoimmune fibrinous pericarditis, several weeks post-MI liver glucuronyl transferase deficiency (excretion of conjugated bilirubin) XLR frameshift mutation, deletion of dystrophin gene, fibrofatty displacement of mm trisomy 18 (after 21, most common trisomy resulting in live birth) faulty collagen synthesis (usually type III, sometimes I, 6 types) uncorrected VSD, ASD, or PDA causes RVH and shunt reversal Rickettsia typhi (fleas) Rickettsia prowazekii (lice) α-galactosidase A def causes ceramide trihexose accumulation

AR, DNA repair gene mutations (ubiquitinization of damaged DNA) proximal tubule resorption defect inflammation from PID (esp N. gonorrhea) spreads to liver capsule

AR (GAA) repeat in frataxin causes mitochondrial impairment

FAP + osseous and soft tissue tumors, retinal hyperplasia β-glucocerebrosidase def causes glucocerebrosidase accumulation dominant parietal lobe lesion mildly low UDPGT or bili uptake, in stress, elevated unconjugated bilirubin GpIIb/IIIa def, no platelet plug formation inflammation and demyelination of peripheral nn (motor>sensory), infiltrate in endoneurium, C. jejuni and HSV are common antecedents, type IV hypersensitivity, high CSF protein, nl cell count defective neutral AA transporter on intestinal and renal epithelium small vessel vasculitis, IgA immune complexes, assn w/ IgA nephropathy; commonly follows URI failure of migration of neural crest cells; no plexuses in intestines iduronate sulfatase def causes heparin sulfate and dermatan sulfate NMDAaccumulation excitotoxicity causes atrophy of striatal nuclei (loss of ACh and GABA) α-L-iduronidasecause loss of motion def causes inhibitors heparin sulfate and dermatan sulfate accumulation failure of addition of M6P to lysosome proteins, so they are excreted instead lysis of spirochetes causes toxin release K channel mutation IFN-γ deficiency, neutrophils don't respond to chemotactic stimuli no migration/development of neural cells dynein arm defect causes immotile cilia medium-sized vessels, self-limited necrotizing vasculitis in infants/kids, esp asians bilateral amygdala lesion peripheral neuropathy, developmental delay, optic atrophy, globoid cells gastric adenocarcinoma mets bilaterally to ovaries Abs against presynaptic Ca channels at NMJ, can be paraneoplastic

defective HGPRT (purine salvage pathway) causing buildup of uric acid

underlying malignancy (mostly GI adenocarcinomas) α-synuclein defect wart-like vegetations, from SLE AD, mutations in p53 cause increased susceptibility to cancers eosinophilic infiltrate and endocardial fibrosis or parasitic pneumonia AD mutation of DNA mismatch repair gene vomiting (alcoholics, bulemics) causes mucosal laceration at GE junction fibrillin defect (scaffold for tropoelastin, makes elastin), lack of elasticity

muscle glycogen phosphorylase def type of polyostotic fibrous dysplasia (bone replaced by fibroblasts, collagen, irregular trabeculae, many bones affected) ovarian fibroma, ascites, pleural effusion (usually R sided transudate), pulling sensation in groin increased gastric mucosal secretion, protein loss, parietal cell atrophy hydrops in labrynth Abs against postsynaptic AChR, worsen w/ muscle use, assn w/ thymoma sphingomyelinase def causes sphingomyelin accumulation

AD inherited disorder of blood vessels high osteoblast and osteoclast activity, abnormal bone architecture; high alk phos, normal Ca and PO4 lesion in superior colliculi (pinealoma) loss of DAergic neurons in substantia nigra pars compacta cause unchecked inhibitory input on thalamus (ACh) trisomy 13

AD, increased risk of CRC/other visceral malignancies frontotemporal atrophy (spares parietal lobe and posterior 2/3 of central gyrus)

iron deficiency lysosomal α-1,4-glucosidase def bilateral renal agenesis (usually ureteric bud malformation) or posterior urethral valves (M, imperforate urethra) TB infxn of 2 adjacent vertebral bodies causes avascularity of disc deletion of paternal chromosome 15 post-GI or chlamydia infxn viral infxn (esp VZV/flu) txed w/ salicylates, aspirin metabolytes decrease β-ox by reversible inhibition of mitochondrial enzyme thyroid replaced by fibrous tissue low liver glucuronyl transferase (excretion of conjugated bilirubin) trigger=aspirin to an asthmatic pituitary infarct more common during birth (N. meningitides) congenital vasculitis, small vessels, sporadic granulomatous thickening of proximal great vessels, seen mostly in Asian F<40 hexosaminidase A def causes GM2 ganglioside accumulation focal granulomatous inflammation of large vessels, seen mostly in elderly F; half of pts have polymyalgia rheumatica failure of migration of neural crest cells of 1st branchial arch paraneoplastic (esp GI adenocarcinoma) FAP + malignant CNS tumors Salmonella typhi, can remain in GB chronically glucose-6-Pase deficiency deletion of VHL (tumor suppressor) on ch. 3 cuses constitutive expression of HIF (hypoxia-inducible factor) causing angiogenesis

lateral medullary syndrome (PICA); lateral spinothalamic, nuc ambiguus, VIII, sympathetics, spinal tract and nuc of V, inferior cerebellar peduncle acute primary adrenal insufficiency from adrenal hemorrhage; from N. meningitides sepsis, DIC, endotoxic shock c-ANCA positive, focal necrotizing vasculitis (small vessels), necrotizing granulomas of the lung/upper airway, and necrotizing GN icterohemorrhagic leptospirosis (spirochete); surfers in the tropics progressive lengthening of PR until beat is dropped AR degeneration of anterior horns (LMN only) bilateral mammillary body lesion (B1 def) bilateral mammillary body lesion (B1 def) superior temporal gyrus Tropheryme whippelii (GP, PAS positive, in macrophages) congenital microdeletion of 7q (includes elastin) inadequate Cu excretion, low ceruloplasmin (conjugated, plasma-safe version of Cu); accumulation everywhere XLR, progressive deletion of BC and TC accessory conduction band (bundle of Kent) bypasses AV node Other aka pseudohypoPTH usually XLR early=APP, presenilin-1/-2; late=ApoE4; ApoE2=protective (degrades plaques) ABCD: Andersen's=branching less severe than DMD aka IgA glomerulonephropathy, adults

tx=nifurtimox

ABCD: Cori's=debranching spongiform cortex tx=plasmapheresis, phototherapy 6 types, severity and inheritance vary

XLR

high CSF protein w/ nl cell count= albuminocytologic dissociation; tx=IVIG, respiratory support, plasmapheresis AR mnemonic: Jenock-S P=Joints, Skin, Panc; commonest childhood systemic vasculitis assn w/ Down's Sz

XLRchromosome 4, AD (CAG)n expansion, anticipation

often fatal in childhood, similar to Hurlers

AR, rare

tx=IVIG, aspirin XLR

aka HNPCC

McArdle's for Muscle mnemonic: POOCH= pit tumors, ovarian cysts, osteomalacia, café-au-lait spots, hyperthyroid

most common NMJ disorder

aka osteitis deformans

rx-induced: metoclopramide, reserpine, haloperidol/chlorpromazine

polyps can cause obstruction aka frontotemporal dementia

Pompe's hits the pump

aka reactive arthritis rare, often fatal aka mycosis fungoides

aka pulseless dz

aka giant cell arteritis

GSD mnemonics: 1-5=VP CAM; PoLys: Pompe's=lysosomal

tx: cyclophosphamide, corticosteroid

aka Mobitz type I 2nd degree heart block aka infantile spinal muscular atrophy stranger would notice friends would notice older men usually aka hepatolenticular degeneration; tx=penicillamine can lead to reentry SVT Neuro Name Sx Huntington agression, depression, dementia, chorea, athetosis (writhing fingers) Parkinson pill-rolling tremor (at rest), cogwheel rigidity, brady-/a-kinesia, postural instability Alzheimer dementia, can get intracranial hemorrhage

Pick's Dz (FTD) dementia, aphasia, Parkinsonian, change in personality Lewy Body dementia Parkinsonism w/ dementia and hallucinations Creutzfeldt-Jakob Dz rapidly progressive dementia with myoclonus normal pressure urinary incontinence, ataxia, dementia hydrocephalus MS internuclear ophthalmoplegia (nystagmus, dyplopia), scanning speech, intention tremor, incontinence, optic neuritis (loss of vision), hemisensory sx; relapsing/remitting ammonia intoxication tremor, slurring speech, somnolence, vomiting, cerebral edema, blurred vision pellagra diarrhea, dementia, dermatitis (glossitis) Renal Immune deposits Sub-epithelial Membranous GN Postinfectious GN Lupus nephritis V

Immunofluorescence Pattern Granular Membranous nephropathy Postinfectious GN Membranoproliferative GN

Other Characteristics Difuse Glomerular Proliferation Postinfections GN Membranoproliferative GN SLE

Microbio Name Pathophys von Gierke's Dz (type I) glucose-6-Pase deficiency Pompe's Dz (II) lysosomal α-1,4-glucosidase def Cori's Dz (III) debranching enzyme (α-1,6-glucosidase) def Andersen's Dz (IV) branching enzyme def, glycogen pptation McArdle's Dz (V) muscle glycogen phosphorylase def Gaucher's Dz β-glucocerebrosidase def causes glucocerebrosidase accumulation Krabbe's Dz galactocerebrosidase def causes galactocerebroside accumulation Fabry's Dz α-galactosidase A def causes ceramide trihexose accumulation Tay-Sach's Dz hexosaminidase A def causes GM2 ganglioside accumulation Neimann-Pick Dz sphingomyelinase def causes sphingomyelin accumulation Hurler's Sz α-L-iduronidase def causes heparin sulfate and dermatan sulfate accumulation Hunter's Sz iduronate sulfatase def causes heparin sulfate and dermatan sulfate accumulation I-cell (inclusion) dz failure of addition of M6P to lysosome proteins, so they are excreted instead metachromic leukodystrophy arylsulfatase A deficiency causes cerebroside sulfate accumulation Vasculitides Name Pathophys Wegener's granulomatosis focal necrotizing: vasculitis, granulomas of upper airways/lung, and GN; c-ANCA 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-ANCA Sturge-Weber congenital vascular disorder, small vessels

Henoch-Schonlein purpura IgA immune complexes, assn w/ IgA nephropathy

Buerger's dz idiopathic segmental thrombosing vasculitis of medium vessels, seen in heavy smokers Kawasaki's Dz acute, self-limited necrotizing middle-sized vasculitis, in infants/kids, esp asians Takayasu's arteritis granulomatous thickening of proximal great vessels; Asian F<40, high ESR temporal arteritis focal granulomatous inflammation of large a Neuro Pathophys NMDA excitotoxicity causes atrophy of striatal nuclei (loss of ACh and GABA) cause loss of motion inhibitors loss of DAergic neurons in substantia nigra pars compacta cause increased inhibitory input on thalamus APP degradation by β-/γ-secretase yields N-APP (DR6L) or Aβ40/42 (cell death signal or aggregate into plaques) frontotemporal atrophy (spares parietal lobe and posterior 2/3 of central gyrus) α-synuclein defect prions cause α-helix to β-sheet transformation expanding ventricles cause corona radiata distortion (no increase in subarachnoid space volume) autoimmune inflammation and demyelination of CNS; commonly hits MLF, optic nerve, spinal cord

NH4 depletes α-KG, inhibiting TCA cycle; OTC is most common urea cycle disorder B3 def (can be from Hartnup's, carcinoid sz, low B6) Renal Immune deposits Sub-endothelial Cryoglobulinemia Membranoproliferative GN Lupus nephritis III-V

Immunofluorescence Pattern Linear Goodpasture's

Other Characteristics Low Complement Postinfectious GN Membranoproliferative GN Cryoglobulinemia SLE Microbio Sx severe fasting hypoglycemia, increased glycogen in liver, hepatomegaly, lactic acidosis, gout, cardiomegaly, muscular, neuro sx mild form of von Gierke's (gluconeogenesis intact) cirrhosis and death w/i 5y cramps, myoglobinuria w/ exercise HSM, aseptic necrosis of femur/bone crises, Gaucher's cells (macrophages look like crumpled paper) peripheral neuropathy, developmental delay, optic atrophy, globoid cells peripheral neuropathy (esp hands and feet), angiokeratomas, cardiovascular and renal diseases progressive neurodegeneration, developmental delay, cherry red macula, lysosomes w/ onion skin, no HSM progressive neurodegeneration, developmental delay, cherry red macula, foam cells, HSM developmental delay, gargoylism, airway obstruction, corneal clouding, HSM mild Hurler's, no corneal clouding, aggressive behavior

Hurler's, + restricted joint movement, high plasma levels of lysosomal proteins, gingival hyperplasia cerntral and peripheral demyelination with ataxia, dementia

Vasculitides Sx cough, dyspnea, hemoptysis, chronic sinusitis, otitis media, hematuria/RBC casts, mastoiditis

usually asthma, sinusitis, skin lesions, peripheral nephropathy; can also involve heart, GI, kidneys facial port-wine stain (nevus flammeus), ipsilateral leptomeningeal angiomatosis, seizures, early glaucoma palpable purpura on thighs/butt, arthralgias, intestinal hemorrhage, abdominal pain, melena intermittent claudication, superficial nodular phlebitis, Raynaud's, severe pain, can cause gangrene fever, conjunctivitis, strawberry tongue, lymphadenitis, desquamative skin lesions, can cause coronary aneurisms fever, night sweats, myalgia, arthtiris, skin nodules, weak pulses in UE, ocular disturbances jaw claudication, unilateral headache, vision disturbance Neuro Other

chromosome 4, AD (CAG)n expansion, anticipation; drug-induced: haloperidol/chlorpromazine, reserpine, metoclopramide Lewy bodies (α-synuclein intracellular inclusions)

cortical atrophy, decreased ACh, intracellular neurofibrillary tangles (hyperphosphorylated tau); early onset=APP, presenilin-1/-2; late=ApoE4; ApoE2=protective (degrades plaques) aka frontotemporal dementia; Pick bodies (hyperphosphorylated intracellular tau)

spongiform cortex

CSF: increased protein (IgG, oligoclonal bands are dxtic); periventricular plaques (oligodendrocyte loss, reactive gliosis), preservation of axons; tx: β-IFN, immunosuppression, sxatic tx for neurogenic bladder, spasticity, pain tx: benzoate, lactulose, or phenylbutyrate (bind AAs and lead to excretion in urine)

Renal Immune deposits Mesangial Berger's Dz (IgA nephropathy)

Lupus nephritis II-V

Immunofluorescence Pattern Light and Dark Areas Berger's Dz (IgA nephropathy)

Other Characteristics

Microbio Other GSD mnemonics: 1-5=VP CAM Pompe's hits the pump; PoLys: Pompe's=lysosomal ABCD: Andersen's=branching, Cori's=debranching

McArdle's for Muscle most common

XLR

XLR

Vasculitides

most common childhood systemic vasculitis

aka thromboangiitis obliteralns

tx=IVIG, aspirin

aka pulseless disease

high ESR, mostly in elderly F, half of pts have polymyalgia rheumatica Cardio disease tx essential htn diuretics, ACEI, ARBs, CCB htn in CHF diuretics, ACEI, ARBs, CCB, β blockers htn in DM ACEI, ARBs, CCB, diuretics, β-blocker, α-blocker 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 absence seizure first line: ethosuximide; otherwise, valproate status seizure acute: BDZ; prophylaxis: phenytoin Cardio other

no β blockers in decompensated CHF, esp K-sparing diuretics ACEI protective against diabetic nephropathy

Neuro

first line in pregnancy and children: phenobarbital -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