General PrinciplesBehavioral Science Learing and Behavior Therapy Candoning. 4 Dienst Somaotorm Dsaders om FecicausDsrdess Types Renlocenen. A and Malngeng 8 Rercermert Schedules 4 ermal Disord. 2 Leaming Based Terie, 5 Drum Versus Denertn % Child Development Carman Abramalies on Nerleg Barintion 2s infer Deopren. 5 Sexual Disorders Figues Copied and Arpoxnat aes 5 Perlis 26 ey Deebrentl ems 6 ender enya Prefered Sena Pare of Blog le 26 Che's Concepon fess and Death 7 Sens Dore oe 2» Cid Deveopet Milsons ooo ccc 7=8—Physiden-Patient Relationships ‘Tyescf Abuse and Inport ses, a Gove ies, 2-28 Sleep: Physiology and Disorders ical and Lega sues Slee Psilny 9 Gera es. nes Changes Dg he Fist Tee Hous of Sep. 9 Biostatistics Stes Disrdors wo Incidence and Preece 2 ght eos Vsus Nighi D “ypesof Marat aes 2 Deferse Mechanisms Screening Resisina 22 table 2 Commo FreuanDelense Mechanisms " Healy and Diseased Popdaions Monga Sceerng Dimension... 32 Substance Abuse “Wpesof Basin Reseach and mporat Assciaions 3 cota a 0 Diferertixng Osenatona utes, 8 Drugs Abuse tel Making Decsons Using Vb. 3B Psychopathology Conenc ites 34 Five Majo grt us, 15 Tes Soles in Stasis a ent Retardation 6 “Wpesol Soe and Bas Sats Tess a Fervsve Deveopmera sade: tim 5 Atenton DefictyperadiyDsxde @DMD) 16 Sehinepuei 6 Anpythsc Medco An Oven . v Side ect ofp Anipsyehoe Meats. v raya Side is fa Aypolaniorat ta aod Dasrdes Oven ta Mood Disorder Subtypes 8 onal Ge Versus Depression n Anidepressns 20 Ecracave Therap (ECT) 20 tithiam » aig Ds, foe 2a Anwey Disorder. 2 Sedatveyprasc Orgs, n Inporam Bzoinepines. 2 Semaafom Disncers aLEARNING AND BEHAVIOR THERAPY Classic (Respondent or Pavlovian) Conditioning ues: vcr 1. Learning occurs when an eld response Urconionad Siren > UnconoedRatonsa ‘occurs to a new siimulus. example: A (sgh ol ace (asian) dog salivates to a bell, when proviousiy on salvation occurred only in response to Condsoned Respenoe mest. cs (eaivaen Condcnes Stmuie 2, Key stimulus (belt) must occur before (oon the response, Operant or instrumental Conditioning a 4. Learning occurs when a new response ‘cours f0 an old slimulus. Example: In a ‘Skinner box, the rat now presses the bar ™ ‘no 10 oblain reinforcement. 2, Key stimulus reinforcement must occur Aelnforeament after the response, Mhio--soe ah ieee | wa [Rane Bohavinr(R}. | Stops Punishment Extinction Increases | Past rinorcoment Negative reinforcement UST) oh Ao mei a hoy Schedule Constant Fixed interval (FI) Fixed ratla (FR) hanging ‘Variable interval (V1) Variable ratio (VR) kau, 4 medical‘Systematic desensitization (Often used to treat anxiety and phobias Step 1: hierarchy of stimuli (least to most feared) Stop 2: technique of muscle relaxation taught Stop 8: pationt relaxes in presence of each stimulus on the hierarchy ‘Works by replacing anxiety wth relaxation, an incompatible response Exposure (also flooding or implosion) ‘Simple phobias treated by forced exposure to the feared object Exposuro maintained untl fear response is entinguished ‘Avorsive conditioning Properties ofthe original stimulus are changed to produce an aversive rosponso Can help reduce deviant behaviors Shaping [Achieves farget behavior by reinforcing successive approximations ofthe desired response Reinforcement gradually modified to move behaviors from general responses to specific responses desired Extinction Discontinuing the reinfercement maintaining an undesired behavior "Time out” with children oor test anxiety Stimulus control ‘Sometimes sfimul inadvertent acquire control aver behavier, when this is true, removal of that stimulus can extinguish the response Example: an insomniac only permitted in bed when he/she isso tired that sleep comes ‘almost al once Biofoodback Using extemal feedback to modify internal ;iysilogic states; often uses electronic devices to present physiologic information, e.g, heart manitor to show heart rate ‘Works by means of trialand-error learning and requires repoated practice to be effective Fading {Gradually removing the reinforcement while: 1) witheut the subject discerning the diference and 2) maintaining the desired response Example: gradually replacing postoperative painkiller witha placebo arian medical 5CHILD DEVELOPMENT NZ a Rela Evidenced at | + Reaching and grasping behavior birth + Abiity to imitate facial expressions + Ablity o synehvoniza lim’ movements with speach of athers + Attachment behaviors, such as crying and ellaging Newborn + Profers: characteristics | ~ Large. bright objects with lots of contrast = Moving objects: = Curves versus fines ~ Complex versus simple designs = Facial stimuh (gits more than boys) + Can discriminate between ianguage and nonlanguage stim + AV week old, the infant responds differently tothe smell of mother compared with fthor ‘Smiling + The smile develops from an innate reflex present at birth (endogenous smile) + Shows exogenous emiling intesponse to a face at 8 weeks * A praferential social sil, e.g. (0 the mother's rather than anothers face, appears about 12 to 16 weeks bate ete di NPE aeons) See Jala ciauls niente Brain-growth spurt | + “Criical peri’ of groal vulnerabily to environmental influence + Ertends from last timester of pregnancy through first 14 postnatal months + Size of catica cols and complexity of cellinterconnections undergo their most rapid increase + Distress in the presence of unfamilar people + Appears at § months, reaches peak al 8 months, then disappears after 12 months Disiress of infant after separation rom caretaker ‘Appears at 8 to 12 months: begins to disappear at 20 to 24 months ‘Separation anxlety disorder (school phobia) is failure to resolve separation anxioty ‘Treatment focuses on child's interaction with perents, not on activities in schoolAiles LUA) (os aren tela Mi I-Sy 1). ‘Separation trom parents, punishment, mutation (Freud's castration anxity) mor lkely fo fear: ‘When they become ‘May interpret ness or trestment as punishment (ten have all sets of misconceptions about what is wrong with therm Uni ago S: Children usualy have no conception af death as an ineversile process Only atter age 8 or (Chis realy understands that death i universl, Mevitabla, and inaversibi (oie yeFavstel a Ma Wieeiceh is} Physical and Motor Cognitive, Language Development Social Bevélopment Development Development + Puts evenzhing in mouti |» Parental igure central | + Sensationimovement | + Laughs aloud + Sits with support (4 mo} + Issues of rust are key | + Schemas m0) + Stands with help (6 mo) + Stronger anvisty (6 mo) | + Assimilation and | * Ropettve + Craw, fear of faling (9 mo) | + Play's solitary and accommodation responding (8 mo) + Pincer grasp (12.m0) exploratory : + Fallows abjcts to midine | * Pat-e-cke, peoleaboo (wn) (1070) + One-handed spproachigraep oftoy + Feat in mouth (5 me + Bang and rate stage ‘Changes hands with toy (sme), Year 1 ~ Walk alone (13 me) ~ Separation andely(12mo) | + Achieves obec | » Great venation + Gime sas alone (18.0) | + Dependency on paren’ | permanence in timing of + Emergence of hand figure (rapprochement) language peferenca (18 mo} + Onloakes and paral pay development + Uses 10 words + Kicks bal, throws ball + Stacks theo cubes (18 mo) Year? * igh acy eve ~ Solish end sel-centered | Aworld of objects | ~ Use of pronouns + Walks backward + Iitates mannerisms and | + Can use symbols | = Parents + Cantum doorknob, unsere | actives + Transtion objets | understand most laler + May be aggressive + Strong egocentism | words + Scribbles with rayon + No" fs avodte word + Conerote use of | * Telegraphic + Able to aim to throw bal objects sentences + Stands on iptoos (39 ma) + Twoword + Stacks sb cubes (24 ma} sentences + Uses 250 words + Names body pars Rides treyele * Fixed gender Wentiy - + Completes + Stacks 8 cubes (38 mo) + Soxepecie play sentences + Aterates fet going upstas | + Understands “Yeking turns? + Uses 800 words + Bowel and bledder centro! | + Knows sex and ful names + Undersinds 4 {oe waning) tat + Draws recognizable figures + Strangers oan + Catches ball with arms understand + Cuts paper with seisors + Recognizes common objects * Unbutions butions cermon oo (Continued) médical = 7Aiea mene Pyleal and Motor Cognitive Language Age Devdopment | social Development _| Development Development Year ~ Alaris fet gong down |» Inlation of adut oles | + Pains wand counts | » Cant sores stars + Canosiy about sex playing | ee objects + Uses prpesions + Hopson one foot deter) + Repose our dots | | Uses plats + Grooms tet oruthes tot) | + Mghiares and monster | + Names coors | © Compound fears Sentoncae + agar Years Years ™ Compile epic contol | » Confomiy peers ~ Couns 10 obiecis | > Aske tw meaning + Brain a1 75% of aautweight_ | _ moint covey af words + Draws recopiable man att | * Romantic feng fr ethers + Abstract words ead ody and moe + Oatipal phase hehe + Dresses and undesses st + Catches alin to hands Years 61012 | Boysheavierthangile |» "Rule ofthe game’ are |» Abezace om | > Shit fom » Retned motor ste wey objects coca + Rida Bijele + Oryaizad spre poestia | + Lawof conservation | sod speeth * eins eet kn + Bang team member focal | schievea Irealete » Stondnaonnewases ereary + Adherence tlie | seloncas deine + sepraton tte sexes | + Nofypotateas | + Vectuany + Demanatatng competence | + Memon svetegies | Pm key 1 bow 08 | oumaticaly eal sense of | (60,000 words by rartanavwrong | SON Veasee |= ~ identyisecalasue | Abstracts tom | » Adops personal (adolescence) + Conloriymestinpotent |” abaacions ech patos + neo onus mau Gite tay + Systomate problem. | = Communication eon + Organized spots dminisn |" soMng shatogies | bocomes foc of + avelopenent of primary trmary + Can hale ‘atonshine and secondary seus + Cress genderclanatize. | mypatheals Sharacorstee + Deals wn pst, prevent fre ‘Anoual casos ver 2 rion 510 10% In population | Over 4 illon Most common tye Physiol baernesect | Neglect Physical battery Likely 50x of viet Botore age 5: female 69% fom Fenale ber age 5: male Likely sex of perpatator | Female Male or female Mole Manastony reporiing? | Ves Yea Ne Phystela’s eeponse | Protec and repor Protect and report Counseling ad information inédicalSLEEP: PHYSIOLOGY AND DISORDERS. asda Bese sen Arcos lara Shi age of Sp a Senne se (a= out ove |L ibe Some ove saruce fe BLO pera ‘very sila, . omew fo a Hours ‘Awe iow votage-random fast bota waves Changes of Dally Sep Over the Life Gyele |_Ghanges of Daly Steep Over the Life Gye | penesaeeypraepntnaitar ne] Drowsy-8 to 12 eps-alpha waves otros Wg Aba MO, Stage 1-3to7 ope theta waves: theta ase Aaalanctiref hia Spanneng tba Stage 2-12 to tAepe-sleopspindl and K complexes cueysnte eos Saal phere ae Ah W Data slept 2 pede \ \ Vi REM sleop-ow voltage-random, fast with sawtooth waves mre hentia MWe AWS oun sai aescie ss Human growth hormone (HGH) T Prolactin L Dopamine 7 Serotonin L Thyroid-stimulating hormone (TSH) L nar, medical 9Cea eas Patien offen overweight Risk of sudden death Obstructive: rasping snoring Conirat: Cheyne-Stokes Disorders ‘Signs, Symptoms, and Issues, Narcolepsy + Sleep attacks ‘+ Modafinil: nonamphetamine alternative to + Gotaplexy CONS stimulants + Hypnagogic hallucinations + Traditionally treated with CNS stimulants * Sleep paralysis (e.9,, amphetamines) + REM latency €10 minutos Sleep apnea ‘+ Absence of respiralion fr extended periods Weightloss ‘syndromes during sieep + Continuous positive airway pressure (CPAP) * Condition so sleeping postion not on back + Sungery for severe cases ‘Sudden infant death Unexplained death in chicren younger than 1 year + Lay baby to sleep on back + Hypnotic medication abuse + Emotional problems + Conditioned poor sleep + Withdrawal from drugs ‘syndrome (SIDS) + Avoid overstuffed becding and pillows + Rate higher if household member smokes + Fetal exposure to matemal smoking is strong risk factor Insomnia Causes: + Behavioral therapy best treatment + Pharmacclogy: acute relief by benzodiazepines, zolpidem, zaleplon, ‘eszopiclone (no tolerance) Boys 2x more than girs Defense mechanism of regression + Stage 4 sleep Identiy anxiety issues + Ifwakened, person confused and disoriented Enuresis (bedwetting) | + Delta sleep Imipramine acutely Bruxism (teeth gringing) Silage 2 sleep Pationt may be unaware unless fold by others Reduce anxiety, oral devices Sloop stage Stage 4 (dalla sleep) REM Physiologie arousal Extreme Elevated Reeall upon waking No. Yes Waking time anxiety Yes, usually unidentified ‘Yes, often unidintiied Other issues. + Runs in famiies + Mote comman in bays + Gan be a precursar fo tompora lobe evilepsy + Common from ages 3 10 7 + Desensitization behavior therapy provides marked improvement 0aay =a tel) ferel Mel Mae eaielae ee Iinportant Associations Defense ‘Shart Definition 2 : Mochanism : Projection ‘Atibuting ner eating fo others Paranci behavior | Denial Saying it isnot 80 ‘Substance abuse, reaction to death Splitting ‘The world composed of polar opposites Borderie personality. good versus evil Blocking “Transient inability to remember Momentary lapse Regrossion Returning to an eae Stage ot develapment | Enuresis, primitive behaviors ‘Somatization | Physical symptoms for psychological reasons Sorrateform disorders Introjection The outside Becomes inside Superego, boing lke parents Displacement Source stays the same, but iarget changes Redirected emotion, phobias, scapegoat Repression Forgeting so itis nonretriovatle Forget and forget Tnolation of affect | Facts without feeting Bluntod affect, a belle inaiference Intelectualization ‘Aft replaced by academic content ‘Aeadamic, not emotional, reaction ‘Acting out Aiect covered up by excessive action or sensation Substance abuse, fighting, geting Rationalization Why the unaeceptable is okay inthis instance stification, string of reasons ‘Reaction formation “The nacceplable transformed into its opposite Manifesting the opposite; fee love but show hale: "Girls have cooties.” Undoing ‘Acton fo symbolically reverse the unacceptable Fiving or repairing, obsessive—compulsve | ‘pohaviors Passive-agaressive | Passive nonperformance aftor promise Unconscious, indirect hostility Dissociation Separating Se from one's ow experience Fugue, depersonalization, amnesia, multiple personality Humor A pleasant release from anxiety Laughter hides the pain ‘Sublimation “Moving an unacceptable Impulse into an acceptable | Art, ilerature, mentoring ‘channel ‘Suppression Forgottng, but i retrievable Forget and rememberea Key Concepts SUBSTANCE ABUSE Most costly health problem 10% of people are problem drinkers Havy drinking increasing in younger people ‘Accounts for 50% of auto accident deaths ‘Leading known cause of mental retardation (feta alcohol syndrome (FAS}) Genetic vulnerability activates by environment and behavior Capacity to tolerate alcohol confers greatest risk Medical Complications Cimhosis, alcoholic hepatitis, pancreatitis, gastic or duodenal ulcer, esophageal varices, middle-age onset of diabetes, ‘gastrointestinal cancer, hypertension, peripheral neuropathies, myopathies, carciomyopathy, cerebral vascular accidents, erectile dysfunction, gout, vitamin deficiencies, pemicious anemia, and brain disorders, including Wericke-Korsakoff syndrome (mortality rate of untreated Wernicke is 50%; treatment is with thiamine) Main Treatment: Alcoholies Anonymous “Twolve-step program, consists of meetings and sponsors; least expensive; believed to be mast successful Pharmacologic Treatment (Antabuse®) chest pain, hyperventilation, tachycardia, vomiting; effective for short-term treatment only coos oni TET “we om at Tahydrogerase > Aestaldehyde nase 4) twat 1 iit. sen a ‘NEV 1] Sumessmesn [TED tles aa “The chronic user can experience an alcohol withdrawal syndrome upon discontinuance of ethanol consumption. Symptoms include anxiety tremor, insomnia, and possibly delirium tremens (DTs) and life-threatening seizures; arrhythmias, nauseal vomiting, and diartiea may also occur. + Treatment includes thiamine, sedalive-hypnotics with gradual tapering; clonidine and propranolal ae useful to correct the hyperadrenersia state of witherawal 2 medicalcocaine Blocks DA, NE, | Euphoria, Cardiac anhymias, | Craving, depression. (cracks BHT reuptake (also | hyperviglance, axity, | myocardial infarction, | fakque, T smokable form) | local anesthelc) | stereotyped benevor, | sate, haluciaions, | T apple ‘randosiy, tcrycaria, | paranoia, Pupiary dation. © fypertnermia, appetite seizures, death Troatment 825, ‘Amphetamines | Releases DA, NE (speed, co are | SHT, weak MAO cee aunporh ‘smokable forms) | inter fers. supper Both: NE most important for peripheral eet; DA mast important for central elects ONS depressants Benzodiazepines | T fequency ot | Light to moderate CHS | Impaired judgment, | Arey, dtu, GABA, channel | depression slures speech, insomnia, porsible opening tincerdination, Hoctyeatening sotures unsteady galt Treatmont long sing stupor respiratory "G2 1p suppress acule fomesson deat | symptoms taper dose Barbiurates | t duration of can produce Font | “or Bz overdose, GABA, channel | severe CNS depression | Sipportve care openiny {EIOH, baroturates) crose-eerance, Ethanol (E10H) ‘ivy among crogs (see previous tthe cass tables Opioids (hercin, woroine, | stimutate xx, | Euphoria. analgesia, | Respiratory Goosatish (old oxycodone) ‘Breceptors; w ‘sedation, cough depression, nausea! turkey’), diarrhea, receptormost | suppression, miosis | vomilin, miosi, ‘hinrthea, sermaton, imporantin abuse | (except meperidine), | sacaton, coma, death | sweating, yawning, conetipation sheatmant nalorene. | muscle orks (hiking retrain the habit) very naltrexone, supportive ‘unpleasant but not fie- threatening Treatment: methadone, LAM, buprenorphine, onidine (Continued)Drucs oF ABUSE (GonT'p,) Cannabis: (ovarjuana Binds 8, and | Euphoria, disinhibition, | Amotivational Mid ietabittyranety ‘arass;"hashis) | C2, cannabinoid | perceptual changes, "| syndrome, respiratory receptors reddened conjunctiva, | effacts ‘dry mauth, T appetite, antiemetic effects (dronabino! used as antirmatic) Hatlucinogens (180, mescatine, | Interact wih SHT | Pereoptua change: io reaction Minima because of Baiocybin) recepiors synesthesias (Le, ad ip’) possible, | lack of physiologic dependence ‘Aseaulive, combative, impulsive, agitated, nyslagmus, ataxia, muscle rigidly, response to pain, hyperacusis, parancia, unpredictable violence, psychosis, hypertension, ife-threatoning ‘seizures + Ketamine, a congener of PCP, also abused MDMA (‘acsiasy’) + SHT releasers (amphatamine-iike mechanism, except releases more SHT than dopamine) + May cause damage to serotonergic neurons; causes hyperthermia; popular in "raves" Anticholinergics Deliriant effects, ¢.9., Jimson waad, scopalamine; psychotic and anticholinergic offects Nicotine + Tobacco use associated with cardiovascular, respiratory, and neoplastic disease + Nicotine patches and gum; bupropion used for cessation inhalants (gue, solvers) impaired judgement, uncoordination; causes muliple organ damage Definon of abbreviations: 82, benzodiazepine; DA, dopamine; HT, serotonin; LAM, levo-c-ecelylmethadol: LSD, lysergle acd sothylaride; MDMA, mathyienedhoxymatnarphetamine; NE, norepinootrine; CV, cardlovescular. warcaw, medicalPSYCHOPATHOLOGY + Also includes anorexia nervosa, bulimia nervosa, sexual disorders, sleep disorders, and autism ‘Axistt | Personatity disorders and | Personality diserders and mental retardation mental retardation ‘Axis |_| Physical conditions and Any physical diagnosis disorders ‘Axis IW | Psychosocial and Includes primary support group, social occupation, education, housing, ‘environmental problems —_| economics, health care services, and legal issues ‘Axis V__| Global assessment of ‘Scored on a descending scale of 100 to 1, where 100 represents superior ‘unetioning (GAF) functioning, 50 represents serious symptoms, and 10 represents porsietent danger of hurting self or others Mile 701050 | + Selt-supporting with some guidance + 85% of retarded persons. Two times as many are male + Usually diagnosed first year in schoo! Moderate | 491095 | + “Trainabie” + Benoft from vocationat training, but need supervision + Sheltered workshops Severe | 341020 | » Traling not helpful + Can earn fo communicate + Basie habits Profound | Solow 20 | + Need highly structured environment, constant nursing care supervision panes Moguls eoess ssh Ganeral Usually diagnosed during age 2 y characteristics | Malefemae raio—4:1 + 80% have Ids below 70, ‘Clinical signe + Problems with reciprocal socal Interaction + Abnormalidelayed language development, impaired verbal and nonverbal communication + No separation anxiety + Oblivious to extemal word + Fails to assume anticipatory posture, shrinks from touch + Preference for inanimate objects + Slereotyped behavior, decreased repertore of actives and intorests Potential causes | ~ Association with prenatal and perinatal injury, e.g, rubella in first timester + Possible role of environmental mereury exposure + Proposed mechanism: fallure of apoptosie in cortex “Treatment * Behavioral techniques (shaping) ara, medical 1see acne eee cu aad esc saGOn ey Mele to female ratio—10:1 + Overtreatment is common; dlferentiate from child whois simply “overactive” General comments Clinical signs + Difcuty sustaining attention: cif with organization, easly distracted, often does not ston when spoken io, eset complete tasks + Hyperactuty: fgets, often leaves sea in classroom, ificuly playing quel, talks axcassivaly + Impuisvty:itorupts others, burs out answers, fculy waiting tum ‘Treatment * Behavior terapy Drug therapy: methylphenidate, devioamphetamine, atomoxetine eae ctor + Bizarre delusions + Auditory hallucinations jin 75%) Blunt affect Loose associations + Deficiency in salty testing, distorted perception; impaired functioning overall + Disturbaness in behavior a frm and content of language and thought + Changes in psychomotor behavior, oss of prosody + Sympioms for anger than 6 months Onset male, ages 15 © 24 female, ages 25 0 34 Prevalence: 1% of population crosscutraly + More often in low social economic status + 50% patents attempt suicide; 10% succeed Epidemiology Neurochemisty | - “Dopamine hypothesis of schizophrenia’ suggests that symptoms arise because of a functional ‘excess of dopamine activily in the CNS (mesoiimbiclmesocartical pathways) + Serotonin and gllamate may also play roles a eae SUnnOE e ‘Paranoid * Delusions of persecution or grandeur + Often accompanied by hallucinations (voices) Calatonie ~ Complete stupor or pronounced decrease fh spontaneous movements + Atematvely, can be excited and evidence extreme motor ataton Disorganized | + Incoherent primitive, uninhibited a + Unorganized behaviors and speech Active, but aimless Pronounced thought disorder Undifferentiated —_| + Psychotic symptoms but does not it paranoid, catatonic, or disorganized diagnoses Residual Previous episode, but na prominent psychotic symptoms at evaluation ‘Some lingering negative symptoms medicalDAN eL eas le ule eeu mena) Clinical uses ‘Antipsychotics (neuroleplics) are used in a varity of clinical settings, including schizophrenia, ‘schizoaffective disorders, mania (with Ithium, initial management), Toure syndrome (malindone), preoperative sedation (promethazine), drug or racalion emesis (prochlorperazine). ‘and neurcieplie anesthesia (droperidol. Antipsychotics unfortunately affect all dopamivergic tracts in the brain, including the mesolimbic/mesocortical(\hought and mood), the nigrostriatal (extrapyramidal motor), and tuberoinfundibular (dopamine inhibits prolactin release) pathways. The goal isto block ‘the mesolimbicimesocotical pathways, but sie offects result from tlocking the nigrostriatal (extrapyramidal side effects [EPS)) and tuberointundibular (hyperprolactinemia) pathways, Typlesl antipsychotics | This older group of antipsychotics falls inio two general categoria: high potency and low potency (see fable below). Their mechanism of action is thought to be related primey to their bility block D, receptors. “Atypical antipsychotics | Newer group of antipsychotics; in general, weaker D, receptor antagonists and stronger SHT, A Antagonists. They also have less EPS. Si leaascutos Unies Maaco aod ues + The high-potency drugs block DA receptors wall (cause more EPS), 50 a low drug dose can be used, minimizing other nonspecific side effects (x blockade, antimuscarinic effects, sedation) + The low-poteney drags do not Block DA receptors as wel as high-potency drugs do, and a higher dose is requied, ‘Therefore, there Is lass EPS and more nonspecific side effects. + The nonspecific side effecs include orthostatic hypotension, male sexual dysfunction (a tiockade}; constipation, dry mouth, urinary retention, visual problems {muscarinic blockade); and sedation ‘+ Hyperprolactinemia may occur due to D, receptor blockada in the pituitary. + Neuroleptic malignant syndrome, which is potentially life-threatening, may occur. Symmploms include oxtreme muscle Figidiy. Nypethermia, and autonomic instabiily. Treatment may include dantrolone and dopamine agonists, + Wieight gain and © decrease in the seizure threshold may also occur, Potency EPs Nonspecific Side Effects High Low High {haloperidol fuphenazine) Low Low High (chlorpromazine, thioridazine") Denton o abbreviations: DA, dopamine; EPS, extrapyramidal side effects. “Thiordazine can cause retin! deposits, leading to visual problems, and conduction defects thet may result in fatal ventricular arrhythmia. WiticalEXTRAPYRAMIDAL SIDE EFFECTS Early Onset and Reversible c Dystonia * Involuntary contraction primarly of the face, neck, tongue, and extraocular muscles + Rosponds to anticholinergics Parkinsonism + Akinesia, muscle rigidity, tremor, shufing galt (ypically appearing in that order) ‘Axathisia + Motor restlessness and the urge to move Late Onset and Irreversible Tardive dyskinesia | « Diagnosis requires exposure to neuroleptics for atleast 3 months, but often takes longer (To) + Involuntary repetitive movements of ips, face, tongue, ibs + Try to prevent by using lowest possible dose 6f antipsychotic medication + Antchalinorgics worsen TD + Try to reduce dose or discontinue madication i TD occurs (although increasing dose wil temporary mask symptome) + Switch to an alypicl antipsychotic Ui ea Mlle healed Drugs Characteristics | Side effects Clozapine + Generally good SHT, antagonists and weaker + Clozapine: agranulocytosis Risperidone D, antagonists + Ziprasidone: profongs QT interval, ‘Olanzapine + Treats postive and negative symptoms of schizophrenia | may lead to lorsades uetigpine (typical treat mastly postive) + Risperidone: some EPS. Zprasidone + Less EPS ‘iiprazole + Tend lo be more expensive than typicals “Clozapine blocks B, ralher than D,, receptors. ‘Stable Alternating Unipolar (major depression) Bipolar (manic depression) imédicalWee eenassusaiees Types Character Dysthymia + Depressed mood + Loss of interest or pleasure + Chronic (atleast 2 years) yclothyria ~ Ailemating ates (conpsychotic bipolar) | rronic + Often nol recognized by afacted person ‘Seasonal affective + Depressive symptoms during winter months (shortest day, 60 least amount of ght) disorder (SAD) + Caused by abnormal melatonin metabolism + Treat wit bright ight therapy Unipolar depression + Symptoms fr atleast 2 weeks {major depression) + Must be @ change from previous functioning + May be associated with anhednia, no motivation, feelings of worthlessness, decreased concentration, weight oss or gain, depressed mood, recurrent thoughis, insomnia or twypersomnia, psychomotor agitation or retardation, somatic complaints delusions or lucinations (need congruent oss of 88x drive + jumal improvement as day progresses + Suicide: 60% of depressed pationts have suicide ideation; 15% se by suicide + Neurochomisty: “biogenic amine theory of depression'—caused by decreased NEISHT + Sleep: 7 REM in fit half of aleep, REM latency, {stage 4 sleep, T REM time overall, early morning wakening Bipolar disorder + Symptoms of major depression and symptoms of mania (period af abnormal and persistent (manie-depression) elevated, expansive, of initable mood) + Subtypes: = Bipolar I: mania more prominent = Bipolar I: recurrent depressive episodes, plus hypomanic episodes ~ “Rapidly cycling bipolar disorder": If altemales within 48-72 hours “+ Manic symptoms: 7 sal-esteem or grandiosity, low frusiratior tolerance, J need for sleep, fight of ideas, excessive involvement in actives, weightloss and anorexia erraitc uninhibited behavior, 7 Hbido Dafaiion of abbroviatons: BHT, serctorin, NE, norepinephrine; REM, rapid eye ovement. (Nel sal cilgn aa stossg-cco Normal Grlef Depression Normal up to 1 year Longer than 1 year, sooner if symptoms severe Crying, | Fbido, weight loss, insomnia Same Longing, wish to see loved one, may think they hear or see loved | Abnormal overidentiication, personality change one ina crowd Loss of oer Loss of set Suicidal Keaton rare Suicidal ideation common Seleimited, usually <6 manths Symptoms do not stop (may persist for years) Aieproasants not helpful “Antidepressants helpful HdicalEigse Class/agents ‘Mechanism Side Effects and Comments Tricyclic antidepressants (TCADs) Block reuptake of NE and SHT | + Anticholineraic (amitriptyline, imipramine, nortiptyine, + Apna blockade desipramine) + Sedation + seizure threshois + Overdose: triad ('3 Cs"): coma, convulsions, cardiotoxicity + Drug interactions: do not mix with SSRIs land MAOIs; potential fatal Heterocyctics Mechanism varies + Trazodone causes priapism, sedation (amoxapine, bupropion, maprotilin + Amoxapine causes EPS (also dopamine {razodone, mirtazapine, nefazodone, receptor blocker) venlafaxine) + Maprotiine, amoxapine: seizures, cardiotoxicity + Netazodone, venlafaxine: P450 inhibitors + Bupropion used in smoking cessation Selective serotonin reuptake Inhibitors | Blocks reuptake of SHT + Anxiety, agitation, insomnia, (SSRIs) + Nausea, (luoxetine, sertraline, citalopram, : fran, prie «Seon syndrome uso ty hyperthermia, myoclonus, ANS instabiliy), ‘seizures occurs with TCADs, MAOl ‘meperidine, dextromethorphan MAO inhibitors (MAOIs) Interfere with melabotsm | = Onthostatic hypotension, weight gain (Ghenelzine, ranycypromine, OINE and SHT by Blocking | «Hypertensive criss i palit consumes ‘eocerboxazid) ‘monoamine oxidase (MAO) food wih tyramine and othe Indvect- acing types A and B. ‘sympathomimetics + Serotonin syndrome when combined wih serie Peeper enc) ‘Common uses: + Side effects: = Depression (80%) — Anesthesia eliminates fractures and anticipatory = Schizoatfective disorder (10%) anxiety = Bipolar disorder ‘= Memory loss and headache common, ratums tc 90% show some immediate improvement normal in several weeks, Usually requires 5 to 10 treatments = Serious complications <1:1,000 ‘Treats depressive episodes, not for prophylaxis * Gontraindication: T cranial pressure (e.g., tumor) + Used in bipolar disorder ‘+ Mechanism not well understood but may inhibit the recyciing of neuronal phosphoinositides + Used in conjunction with antidepressants + Neurcleptics andior benzodiazepines may be used iiially because Ithium has very slow onset + Very narrow therapeutic Index + Side effects: sedation, ataxia, tremor, reversible nephrogenic diabetes insipidus, edema, acne, leukocytosis + Neonatal toxicity it administeres to pregnant women + Valproic acid and olanzapine are also used in bipolar disorder 20Eatine Disorvers Characteristics: ‘Anorexia Nervosa limia Nervosa ‘Sex Pom Foi Age Mid-teenage years ate adolescence/early adulthood Socioeconomic status (SES) | May be high or low ‘May be high oF low Weight >15% ideal body weight loss Varies, usually nocmal ot > normal Neurotransmitters: Serotonininorepinephrine? ‘Serotanininarepinephvine? Bingelpurge Yes Yes Laxative/diureties Yes Yes ‘Sexual adjustment Poor Good Medical complications . + Dental caviies| : + Calluses on handsiingers : iy + Enlarged parotid glands + Dental cavities + Electrolye imbalances + Electrolyte imbalances + Cardiac abnormalities Cardiac sbnormaii | ANXIETY DISORDERS. Generalized anxiety + Symptoms exhibited more days than not for longer than a 6-mnh perlad disorder = Motor tension (Rael. jumpy) = Autonomic hyperactivity (heart pounding, sweating, chest pains), hyperventilation ~ Apprehension (fear, worry rumination), dificity concentrating = Vigtance ard scanning (impatient, hyperactive, distracted) ~ Fatigue and sleep disturbances common, especialy insomnia and restlessness + Treatment: benzodiazepines, buspirone ‘Specific phot ‘+ -Aneely when faced with identifiable object (ear of specific object, | + Phobie object avoided 29, spiders, + Persistent and disabling fear ‘Agoraphobia + Also sonse of helplessness or humiliation (fear of open spaces) ‘+ Manifest anxiety, panio-ike symptoms + Travel restricted Social phobia + Leads to dysfunctional circumspect behavior, 0.9. inability {0 urinate in putlie washrooms (fear of feeling or boing | + May accompany avoidant personality disorder stupid, shameful) + Discrete performance anxiety (stage fight): most common phobia; reat with paroxetine (SSRI) ‘oF atenolol or propranolol (bata blocker) Treatment: paroxetine (SSRI) or atenolol or propranolol (bala blocker): for generalized eoclat ansiely, use phenelzine (MAO inhibitor) or paroxetine Obsessive-compulsive disorder ‘Obsession: focusing on one thought, usually to avoid another ‘Compulsion: repelilive action shields person from thoughts, action “fixes” bad thought Primary concetn of pationt isto not lose contro! 1 frontal lobe metabolism, T activity in the caudate nucleus Treatment: fluoxetine, thivoramina, or other SSRI, clomipramine Panic disorder “Three attacks in 3-week period with no dear cleumseribed stimulus ‘Abrupt onset of symptoms. peak within 10 mines Clinical signe: = Great apprehension and fear Palpitations, trembling, sweating = Fear of dying or going crazy Hyperventiiatin, “air hunger” = Sense of untealty Treatment: alprazolam, clonazepam, imipramine‘Sepative-Hypnotic Drucs Class “| Notes, Benzodiazepines + Used as anxiolytcs, hypnotics, anticonvulsants (diazepam, lorazepam, clonazepam), muscle relaxants, for anesthesia (e.,, midazolam) + Binds GABA, receptor and increases frequency of CCI ion channel opening + Dose-dependent CNS depression occurs (nol as ‘much as barbiturates when used alone) + Difforin halfsfe and metabolism + Three 82s are not metabolized in liver: "Out The Liver: Oxazepam, Temazepam, Lorazepam) Barbituratos, + Used 98 anticonvulsants (phenobarbital, long-acting), to Induce anesthesia (thiopental, short-acting) + Binds GABA, receptor and increases duration of Cron channel opening Ineraaing Sadatve Hypnos Dose —> Miscellaneous Zolpidem, zaleplon, and eszopiclone—norbenzodiazepines (used for sleep) Buspirone—nonbenzodiazepine (anxiolytic) iol UA un ss-yrdelel tetas ak Comm. ‘Alprazolam Panic, anxiety Chlordiazepoxide ‘Alcohol detoxification ‘Clonazepam Panic, anxiety, seizures Diazepam ‘Anaioty, insomnia, pre-op sedation, muscle relaxation Flurazepam Insomnia Lorazepam Anxiety, aloohol-rlated seizures Midazolam" Anesthesia Oxazepam ‘Avcohol detoxification Temazepam Insomnia THazolamt Insomnia *Shoriest acing *Short acting cape, medicalSowarororm DisoRDERS Somatlzaton ‘Set cf eight or more symptoms (four pain, two gastrintstinal, one sexual, one peeudcneurologi) ‘disorder Onset before age 20, ‘Symptoms usualy oceur over period of yeara More common in women than in men (20 to 1) ‘One oF more symptoms Altering of physical functioning, suggesting physical disorder Usually skeletal, muscular, sensory, or some peripheral nonautonomic system. €.9., hand, oss of sight Loss of functioning is real and unfeigned + Look for la bell indiference ‘Conversion disorder Hypochondriasis. Unrealistic interpretation ot physical signs as abnormal Preoccupation with illness orfaar of iliness ven none present Preoccupation persis in spite of reassurance Atleast 6 months’ duration ‘Treat by simple palliative care and fostering relationship, | Samatoform pain | - Severe, prolonged pain with no cause ‘ound disorder + Pain disrupts day-to-day life + Look for seaandary gain Bady dysmorphie PPreoccupation with unrealistic negative evaluation of personal attractiveness ‘disorder Sees gelf as ugly or horifie when normal in appearance day-to-day life extreme interventions Fas ULM S oe Moun onlss uracil ea oss sec Wey uIL Un cls oes : Somatoform Factitious — Malingering ‘Symptom production Unconscious Intentional Intentional Motivation Unconscious Unconscious Intentional “Ai reo may present with simar symplom profle. The Kay to he df\ercnil ls level of palent awereness. caruay, medical 23PERSONALITY DISORDERS ‘Types Definition Epidemiology “| Asscciated Defenses, Paranoid Feelings of persecution; feels hat | + Men > women Projection ‘others are conspiring to harm them; | « Increased incidence in familes suspicious with schizophrenia ‘Schizoid ‘solated lifestyle; has no longing for | + Men > women = thers (Toner’) + increased incidence in families with schizophrenia ‘Schizotypal | Eccentvic behavior, thought, and_| + Prevalence is 3% speech + Men > women Histrionle | Excessive emotion and attention | » Women > men + Regression seeking + Underdiagnosed in men + Somatization + Conversion + Dissociation Narcissistic | Grandiose; averconcermed with * Common Fixation at subphase of issues of self-esteem separationindvidualization Borderline | Instability of mood, seltimage, and |» Women > men + Spliting relaionshios + T mood disorders in famiies | + Projective identification + Dissociation + Passive-agoression ‘Antisocial | Does not recognize the rights of | Prevalence: 3% inmen; 1% in | Superege facunae others women ‘Avoidant ‘Shy or timi fears rejection + Common ‘Avoidance + Possible deforming ines Dependent | Dependent, submissive + Common = + Women > men + May end up as abused spouse ‘Obsessive- | Perfectinisic and inflexible, ordery, | + Men > women + Isolation compulsive | ri + Teaneordanee in identical twins | + Reaction formation + Undoing + Intelsctuaization kara, medicaleye eel Delirium TIA, Dementia History Acute identifiable date ‘Chronic, cannot be dated ‘Onset Rapid Insidious Duration Days to weeks Months to years Course Fluctuating Civorically progressive Level of consciousness | Fluctuating Normat Orientation Impaired periodically Disorientation to person Memory Recent memory markedly impaired Remote memories seen 26 recent Perception Visual hallucinations Sleep Less sleep disryotion Reversibility Mosty reversible Physiologie change: Minima Attention span Not reauoee frre eaea esi eu eh oesta ui utead Original Drawing —_—Patient’s Drawing Name Localization 3 iy vnnn rot ‘Constructional apraxia Hemineglect hemi-inattention Nondorninant (right) parietal lobe Right pariatal lobe arian, 5SS ees Pedophitia Sexual urges loward children; most common sexual assault | Exhibitioniam | Recurrent deske to expose genials to strangers Voyeurism ‘Sexval pleasure from watching others who are naked, grooming, or having sex; begins eaty In chiktnood Saaism Sewval pleasure derived trom others’ pain Masochism Senval possure derived trom being abused or dominated Fetish ‘Sexual focus on objects, 0... shoes, stockings. Veriart: transvestite fetishism (fantasies or actual dressing by hoterosexual men in women’s clothing for sexual arouse!) Fréttouriem ile rubbing of genitals against fully clothed woman to echieve orgasm: subways and buses Zoophilia Animals prefered in sexual fantasies or practices Combining sex and defecation Urophilla Combining sex and urination Necrophilia Preferring sex with cadavers Hypoxyphilla ‘Allored state of consciovsness secondary to hypoxia while experiencing orgasm Variants: autoorlic asphyxiation, poppers, amyi nate, nic oxide ‘Common Label Gondor Identity Preferred Soxual Partner 2 Hotorosenuel Male Female Transveste ftshiem Male Female Gender identity serdar (vanssexval) Female Malo Homosenusl Male Male 26 medicalBU aesosaac) Disordérs of Sexual Desire Hypoactive Deficiency oF absence of fantasies or dasires, 20% of population, more comman in women Aversion to all sexual contact ‘Sexual Arousal Disordars Female sexual arousal disorder ‘As high as 33% of females; sometimes hormonally related + Anthistamine and anticholinergic medications 1 vaginal lubrication Male erectile disorder (impotence) + Primary: never able (0 achieve erection + Secondary: once able lo achieve erection = Up to 20% ifetime prevalence; point prevalence 3%, = 50% of men treated for sexual disorders, incidence 7 with age, more likely in smokers ‘Orgasm Disorders ‘Anorgasmia (inhibited fomale orgasm) Inhibited male orgasm (retarded ejaculation) + 5% of maried women older than 35 have never achieved orgasm + Overall prevalence from all causes: 30% + Likeiood to have orgasm T with age + Usually restricted to insbilty to orgasm in the vagi + 5% general prevalence + Differentiate from retrograde ejaculation Premature ejaculation + Male regularly ejaculates before or immediately ater entering vagina + Treatments: slop and go technique, squeeze technique, SSRs Sexual Pain Disordors: Dyspareunia + Recurrent and persistent pain before, during, or after intercourse in either man of woman + More commen in woman + Chronic pelvic pain is a common compat of women raped or sexually abused Vaginiemus + Involuntary muscle constiction of the outer thir oF the vagina + Prevents penile insertion + Treatment: relaxation, Hegar diators medical 2PHYSICIAN-PATIENT RELATIONSHIPS Avaya pac he intrest fhe patent frst | Make pon ak about and krow he pants wishes ‘Always respond tothe patient ‘Respond lo the emotional as wel asthe factual content of, questions. Rule #3: Tell he patient everything, even ithe or she | = The palient should know what you know and when you know it ddoos not ask. + Information should low through the patient to the family, not the Rule #4: Work on long-term relationships with + Good relationships mean good medical practice Pationts, not Just short-term problems. + Make eye contact; both patient and physician should both be siting, iat all possible. Arrange the seting for comfortable, ‘lose communication. If pationt isin oor, tak fo patient, not to colleagues. The patient is always the focus, Rule #5: Listening is better than taking, ‘+ When patient talks, you are learing. + Take time to listen to the patient in front of you, even i ther, paiisnis or colleagues are waiting + Ask what the patient knows before explaining, Rule #5: ‘The patients the decision-maker. Negotiate, do not order Rule #7: Solve the problem presented; anticipate + Find out whal you need to; gat the resources you need, future problems. + Change inital plans as information changes Rule #8: Admit to the patient when you make & ‘Take responsiiliy, dont blame the nursing staff or 8 medical mistake. student ‘Rule #9; Never "pass off" your patient to someone | + Rater to psychiatst or other specialist only when beyond your ase, experts. + Provide instruction in aspects of care, ¢.g.,nvifiion, use of ‘medications, Rule #10: Express empathy, then give contol ‘+ “Tim sorry, what would you ike to do? + lepotant cule to remember when faced with grieving or angry patient oF upset ‘amily members, Rule #11: Agree on the problem withthe patient before | Informed consent requires the patient io fully understand what is moving tothe solution, ‘wrong before ireatmant options are presented, Rule #12: Be sure you understand what the patient is | Seek information before acting, clarify emotionally loaded words, tatking about before intervening begin with open-ended questions, then move lo closed-ended. questions, Rule #13: Patients do not gett select inappropriate | Palients select treatments, but only fram presented, appropriate treatments, choices. Rule #14: Never lose sight of who your patient is, Even if parent or surrogate is making decisions, paiont is sill Uo focus, Rule # 15: Nevor fe, * Do not lie to patients, thet ‘amills, or insurance companies. + Do not deceive to protect colleague. Rule #16: Accept the health beliefs of patients and tak | + Be accepting of benign folk medicine practices. Expect them to them in those terms + Diagnoses need to 06 explained in the way patients can understand, even if not technically precise. Rule #17: Accopt patients’ reugious beliefs and Religion is a source of comfort to many, Ask about a patients Participate, if appropriate 23 «medical religions beliefs i you are not sure. (Continued)GENERAL Rui Pena aa Rule #18: Anything that increases communication + Take the time to talk wih patients, even if others are waiting: ack is good, ‘why, not just what + Seek information about the patient beyond the disease. Rule #19: Be an advocate for the patient + Work to get the patient what he or she neds, + Need, not payment, should decide. Rule #20: How you do it matters as much as what + Focus on the process, not just goals. Means, not ust the ends. you do, + Do the right thing, the right way. + Treal family members with courtesy and tact, but the wishes and interests ofthe patient come first. ETHICAL AND LEGAL ISSUES beatae wey Rules ‘Comments Rule #1: Competent patients have |» ‘Patients have an almost absolute right io refuse the ight io retuse medal | - Patens have almost abslule onl ove the own Bodies realment Rule #2: Assume thatthe patont Competence Isa logal, not a medical seve, A diagnosis, by isl, els you ila is competent unless ciear | about a patient's competence. Clear behavioral euidence would be: behavioral evidence indicates |. Patient aterm suicide. ethervicn, + Patient is grassy psychotic and dystunetional + Patients physical or mental state prevents simple communication Rule #3: Avoid going to court ‘Consider acing to court only it Decision-making should + There is intractable cisagreement about a patients competence, who should be cau in the dnical seting i | the surrogate, or who should make the decision about fe suppor. possible + You perceive serous confit of interest between surrogate and patients intorests + Court approval of decision to terminate ife supports, therfore, rarely required Rule #4: Whon surrogates make 4. Subjective standard Getisions fora patient, they | + Actua intent, advance direcive eee Te oon + What did the patient say in the past? teria and in tis order: 2, Substituted judgment + Who best represents the patient? + What would pationt say ihe or she could? 3 + Burdens versus benefits + Interests of patient, not preferences ofthe decision-maker Rule #5: Ifthe patiantis incompetent, | + Advance directives can be oral physician may rely on + Living wi writen document expressing wishes, advance directives + Health power of attorney: designating the surrogate decision-maker, “speaks ‘with the patiant's voiea™ Rule #6: Feeding ube is a medical | A competent person can refuse avon ifesaving hydration and nutition. ‘reatment and can be withdrawn at the pationts request Rule #7: Do nothing o actively acest |» Passive, ie. allowing o de is okay: activ, i. ling is nat okay the patient to die sooner, But do all you can to reduce the pationt's suflering (e.g, ving pain medication) (Continued) karin, medical 23ee ery Conan oe ale see ted eee) ‘The physician decides when | » What there are no more treatment options (the patient is cortically dead), the pallent Is dead. and the family insist on treatment? if there are no options, there fs nothing the ‘physician can do; treatment mst stop. What ifthe physician thinks continued treatment is futile (he pationt has. shown no improvement), but the surrogate insists on continued treatmant? The treatment should continue. Never abandon @ patient + Lack of financial resources or results are never reasons to slop the treatment of, 2 paint + An annoying or aul patient is stil your patient, Rule #10: Always abtaininformos + The pationt must receive and understand five pieces of information: consent. 1. Nature of procedure 2, Purpase or rationale 23, Benefits 4, Risks 5. Availablity of alternatives + Four exceptions to informed consent 4. Emergency 2. Waiver by patient 8, Palient ig incompetent 4. Therapeutic privilege Rule #11: Special rules apply with * Ghildron younger than 18 years are minors and are legally incompetent. children. + Exceptions: emancipated minors — 1 patients older than 13 years and taking care of self ie, living alone, reat 2s an adult Mariage makes a child emancipated, a8 daes serving In the military, = Prognancy or having a child, in most cases, does not. Partial emancipation ~ Genorally age 14 and older = Consent for cartain esues only: ‘Substance drug treatment Prenatal care ‘Sexually transmitted dis ith contro! 98 treatment ‘ule #12: Parents cannot withhold ife- ts imb-saving treatment from thelr children, It parents refuse permission to treat chil IWimmaciate emergency, go ahead and treat 2. Hnot immediate, but sil crtical e.g. jwvene diabetes), generally the child is declared a ward of the court and the court grants permission. 3. 1 not ite oF limb-tWreatening (e.g., child needs minor stches), listen to the parents. Rule #13; Organ donation should follow | The patient's advance directive should be decisive. Prior dlscussion with family the patient's wishes. members eliminates any contusion as to those wishes. Rule #14: Good Samaritan Laws + Physician is not required to stop and help. lit babi ronmedical | «help offered, shielded from lability provided = Actions are within physician's competence. — Only accepted procedures are performed = Physician remains at scene afer starting therapy unt relieved by compstent personnel —_No compensation changes hands. sottings. (Continued) writ 30 medicalGENERAL RuLes Asour Ethical AND LEGAL Issues (Conr'o.) Rule # 15: Confidentiality is absolute. | + Physicians cannot tell anyone anything abaut their patient without the patients permission, + Physician must stiva to ensure that others cannot access patient information + Getting a consultation is permitted, 26 the consultant is bound by confidentiality, too. However, walch the location ofthe consultation. Be careful not lo be overheard (6.9. in elevator or cafotoria). + Ifyou racelve a court subpoena, show up in court but do not divulge about your patent + If patients a threat to self or others, the physician must break confidentially formation Rule #16: Patients should ba given + DNR refers only to cardiopulmonary resuscitation, tha chance fo stale DNR: * Continue with engoing traatments, (do not resuscitate) orders, + DNR deeisons can bs made by th pation oF surrogate and physicians should alow | | aye DNR aacueslons a pat of your fst encounter wih te pti Rule #17: Conmiti mental i ~ Commited mental 2 aduts are legal ented to he lolowing patents rela the rigs. |” — They must have tesiment avalaie. ~ Thay an rofuse treatment — They can command a jury trial to determine “sanity.” + Thay lose only the ci Ibert 0 come and go Delain pater protect | « Emergency detention can be elected by a physician andra law enforcement thom or others. person for 48 hours, pending a hearing, + Aphysician can detain; only a judge can commit Rule #19: Remove fom patient contact | Types of risks: health care professionals who | = Infectious disease (TB) (Ose risk to patents + Substance abuse + Depression (or other psychological issues) + Incompetence Rule #20: Focus on what is the best | The best conduct is both legal and ethical ethieat canduct, not simply tha latter ofthe law,BIOSTATISTICS Uwe Ne aU dans Number af new events in a specifid pariod 1 ‘Number of persons exposed f0 risk of aquiring the condition during this periog Allcases of a disease at a ven pointiporiod ‘Total population a risk for having the condllion at a given point ot period 0" Incidence rat Provalence rate = x10" BhG-ccog ssueune Us) Crude morality rate Deaths * population Cause-specifie mortality rate Deaths fom cause = population Cause-atality rate Deaths from cause + number of persons wih the dseaseleause Proportionate mortality rate (PMR) Ocaths trom cause = all deaths leita ae pS EMA aca aL ae Present ‘Absent Totals ‘Sereening Test Rosults | Positive | TP 60 re 70 P+ FP ~ | cS | Negative | Fv 40 ™ 30 TN+FN Totas | TP+FN N+P TPH TNs EP + EN Sensitivity = TPATP + FR) Detecting olease Specificity = TNATN + FP) ening heslthy inoiduals Positive predictive value = TPUTP + F®) Wihat % of postive test resulis ill bo corract? Negative predictive value = TNITN + FN) Winat %h af negative test results wil be correct? ‘Accuracy = (TP + TH)/(TP + TN + FP + FN) How good isthe test overall? Dofnition of abbreviations: FN, false negatives: FP false positives; TN, rue negatives; TP, us postoves, eset GUD yea euler Sen Nicene 2, optimal sensitivity and optimal regative precictive value . ential seaciety and opine postive prective , highest accuracy or lowest number of combined flees Remember, wo are looking a cut-of score that best selects the desired group. ‘arian, 32 medicalBhp s sores sG cre ane ASSe Ue St Important Solutien distorts it Type of Bias | Definition Associations Selection ‘Sample not representative Borkson's bia, Random, independent sample ‘onraspondent bias Measurement | The process of gathering information | Hawthome effect, ‘Control groupip'acebo group expectancy Researcher's beliefs affect outcome Pygmalion effect Double-blind design Lead time Early detection confused with Inoreased survival Benefits of screening ‘Measure “back end” surival Ree ‘Subjects cannot remember accurately | Retrospective stucl ‘Multiple sources to confirm . information Late-look ‘Severaly diseased individuals are not | Early mortally ‘Siraty by severity uncovered Confounding | Unanticipated factors abscure results | Hidden factors atfoct ‘Mutipie studios, good research results sign [Yiagas ential ches V Ane est ‘association Characteristic Cross-Sectional Studies Cohort Studies Time One lime point Retrospective Prospective Incidence No No Yes Provatenco Yes No No Causalty No Yos Yes Role of disease Measure disease Begin with disease End wit disease Assesses ‘Association of risk factor and | Many risk factors for single | Singlo risk factor atfoctng disease siscase ‘many cisoasee Data analysis ‘Chisquare to assess (dds rato to estimate isk | Relative sk o estimate risk Possible Outcome #2 Possible Outcome =0.18 (computed p value) Makinc Decisions UsiNG p-VaLues Do NOT Reject Null Hypothesis <1 Fisk of Type tl, B ertor Reject Null Hypothasis Fisk of Type I oorror ps00s S| p= 0.02 (computed p value) Statistical tests are used for ‘making decisions. The p-value generated from the data is ‘compared with p-value criterion selected by the investigator. IF the computed value is less than the criterion value, then reject the null hypothesis, but with a chance of a type | error. If the computed value is greater than the erltrion value, you should ‘not reject the null hypothesis, bout there ie @ chance of a type Merror arta, medical 33efeies esas) Confidence intervals (Cl) estimate the population vale based onthe data roma sample. We give up precision, knowing exacty the population number, in exchange for eonfisence. Confidence intervais tell s tal realy is mest ikely within the spectied range | Confidence intervat of he mean ‘Where: X= sample mean Z = Zscore* '§ = standard deviation N= sample size 1.96 for 95% confidence confidence Confidence intervals for the | If the Cls for two means overlap, then they could be the same. Therefore, we have no | mean ‘evideno® thal thoy are diferent. ifthe Cis do not averiap, then we usually assume that they l are diferent (etalistical significance). In general, any everlap in Cl indicates no difference, Confidence intervals for the Cis contain the number 1.0, then the population parameters compared in the ratio relative risk (RR) or odds | could be the game. Therefore, wo cannot assume that they are diferent. 1.0 is not . ratios included in the Ci, then we assume that they are diferent (statistical significance). A 1.0 in ‘he Gl means that itis not significant, “Type of Scale. Description ‘Key Words Examples. Nominal (categorical) | Different groups "This" as opposed to that” | Gender, comparing arnong treatment interventions Ordinal ‘Groups in sequence Comparative qualiy, nk | Olympic medals, class rank order in medical school Interval Exact diferences emeng groups | Quantiy, mean, and Helght, weight, blood standars devistion pressure, drug dosage Ratio Interval + tue zer0 point “Zero means 7070 Temperature measured in degrees Kelvin Nominal | Comment Poarson cavelation 2 0 Is there a linear relationship? chi-square ° 2 ‘Any number of groups Hest 1 ‘ ‘Two groups only One-way ANOVA 1 1 Two oF more groups Matches peirs tH 1 1 ‘Two groups, linked data pairs, before and ater Repeated measures ANOVA 1 1 More than two groups, inked data Pate medicalBiochemistry Oelyis 36 The GiicAid Cie sr naive Phosphorgation, 38 Praste Metabolism 3% esos Moraghaspte Shar, ” Ciyogeness and Dhcogenohs “ Gluconeogenais . a Amino Ai Structures as Amino Aid Deiat a Ari Ai Sythe and Metbolion 15-46 Uses Cyde a pi Stes and Metaboli, 8 Ketone Body Melbolim 50 Cholesetal Sys coon ene [prrotein Tersprt nd Metaboli x Lipid Devas . 52 rayne Kinetics. ey Water Soluble Varin oA pid Soluble Veins 58BIOCHEMISTRY Glycolysis Ie a eytoplaemic pathway used by all calls o generate energy from glucces. Ona glucose molecu Ie converod info 2 ‘pyruvate molecules, generating a ret of 2 ATPs by substrate-lvel phosphoryaton, and 2 NADHs, When Oxygen Is present, NADH ‘elivers electons to the electron transport chain in mitochondria to generate ATP by oxidative phosphoryation. Under anaeroble ‘conditons (2.8. short bursts of irtonco exorcce) or In cell without mitochondia(e.9., RBCs), laciata la generated ard the NADH is woxiized into NAD nee (set) LUT: T by insu tat and muscte); by exercise (skeletal muse) Galactoxinase daticiency slactosurte, cataracts in hichood (excess galaciose is converted to gelato via ‘Three imeversible steps: o Hexokinase | Glucokinaset Most tssues | Liver only Low Ky High Ky acer @ Insulin e PRK PFK2 roar | 4 F26-8P Rawiritng | Gye ego step T aycolysis atyeotyss + luconsegenesis @ mnsuin ANP F288" | 5 Glucagon GLUT and 3: basal uptake (most cls) GLUT: storage liver); gucose sensor Galactosemiaig akiose reductaso) Tx: ro galactose in ot (Gal--P uridy! transferase daficloncy ‘Same as above, but mre savere win vomitng/alarmea ater mik ingeston, liver ciseuse, lethargy ‘mental retardation; Tx no galactose in cet Fructokinase deficiency Fructosuria; benign Aldolase 8 deficiency Fructosuia, Wer and proximal renal tubule disorder Tx: 0 fructose in dot } ‘Pyruvate kinase deficiency Chronic hemolysis, f2,3-BPG and other glycolytic intermediates in te REC, no Heinz bodies, ‘autosomal recessive Dato ol abredatons: MOD, watre-cel diabetes of ha young: PPK, phcaphalracolinass; RBC, red Hood cal Ts, Yesiment art 36‘The citric acid cycle (trlearboxylle actd cycle) is a mitochondrial pathway that occurs only under aerobic conditions. Each ‘caly-CaA generated from pyrivate is used to produce 3 NADH, 1 FAOH,, and 1 GTP. Both the NADH and FADH, deliver ‘lectrons tothe eleciron transport chain (ETC) to generate energy by oxidative phosphorylation, Asie CO _cctrae in ‘Oxatoscatate od-Aconitate: ait > wpe : 0 e © Kanab + c0,, rete exetgleate aDte\ 1 « Lstonco, ‘\ “2 sertingte Seegevicoh Emre * 2 Senin sthase & eonace &: cert ehycrogenase a 4 kool amtecycepecae © Sucamncon newrase i fee ncey-Con+ 3 NAD" + FAD + GDP+ F, > 2C0, + NADH + ADH, + GTP + Con citrate synthase eate @ icocitrate dohydroganase, (ate-Limiting Step) ADP Sate ‘NADH © ceketoatutarate dehydrogenaset © Suceinyl CoA, Sate NADH “Similar fo pyruvate dehydrogenase complex and uses the same cofactors + Gluconeogenesis (malate shutie) + Fatty acid synthesis (citrate) + Amino acid synthesis (oxaloacetate ‘ad a-ketogiutarate) + Home synthesis (succiny! CoA) kari, medical 37OMe desaosieuen) Electron transport and the coupled synthesis of ATP are known as oxidative phosphoryation. The electron transport chain (ETC) le a series of carrier enzymes in the inner mitochondrial membrane thal pass clectrons, ina stepwise fashion, ffom NADH and FADH, to oxygen, the final elecon acceptor. These caniers create a proton gradiont across the inner membrane, which drives the FyJF, ATP synthase, with a nel production of 3 ATPs per NADH and 2 ATPs par FADH,. Electron Transport Chain Be e Cyanide Poisoning Blocks cytochrome ala: eyanido from buring polyurethane (mattress! furniture stuffing); Tx: nites (creates methemoglobin which binds cyanide) (i Other Inhibitors + Carbon monoxide (cytochrome a/a,) + Antimyein (cytochrome bie,) + Doxorubicin (CoQ) Ty + Oligomyein (F,) + 2,4-DNP (uncobpling reagent’) + High-dose aspirin (uncoupling reagent) + Rotanone (complex I) et > Pe nen Complex |: NADH dehydrogenase ‘Complex ili eytactvome bie, Complex I-succinae detycrogenase | Cyt C: evochvome & -souratze proton raion bce ATP Coa coenzyme @ Complex Nv ytoctreme ey athe E Pew Beton aatiee La Cytosolic electrons are transported into the mitochondria via the malate (fom TCA cycle) and glyeeral-3-P (from DHAP In alyeolysis) carriers Inner ritochondtil Cytosol membrane ‘Mitochondria atx Malate Shuttle Aspartate Aspanate won ~\ ona caemns > mie wae OX won OX we a-GlycerolP Shuttle NADH we Dityroryacotone Ditycronjacetons-P YX FADH, Nao" ° a-Glycorol-P FAD eGlycerol? aru 38 inédicala anes Lactato dehydragonaso: Anzoroblc tissues: converts pyruvate to lactate, riding eytoplasinic NADH to NAD*. Liver converts lactate to pyruvate for gluconeogenesis or for metabolism to acayl CoA Alanine aminotransferase (ALT, GPT): Muscle; converts pyruvate to alanine to transport amino groups to the liver. Liver: converts alanine to pyrwale for gluconeogenesis and delivers the amino group for urea synthesis Pyruvate carboxylase: produces oxeloaceato for glucancogeneeie ane the cic ald cycle Pyruvate dehydrogenase: generates acelyiCoA for fatly acid synthesis and the cic acid cycle; complex of @ enzymes | Pyruvate dehydrogenase (PDH) | asus sons | CADP © AcolyhCoA CoA are NAD © NADH (ome sos eye) @ Insulin’ CCofactors: TPP (trom thiamine, tipole acid, Com 002+ 40 Fat ac cic aed eee Civconsogsnest | (rom pantothenate), FAD {from riboflavin), NAD (from niacin) “Liver specie Pyruvate Dehydrogenase Deficiency Lactic acidosis, seizures, mental retardation, ataxia, spasticity Pyrwate + NAD' + CoA» NADH + CO, + acabi-CoA eae Muscle or ABC | glucose 3", pyruvate —+ lactate During fasting or exercise, acate 1 from RBCs oF skeletal musces is Bloodstream | Sento the Iver to make gcse thatcan be rtumed tothe RBCS oF Liver ‘glucose «+ —+— pyruvate «lactate mmuscie yoconeogenese Definition of abbreviations: TCA, viearboxyle acid; TPP thiomine pyrophosphate arian, Medical 39Gsces= eng eo cuss hue “The hexose monophosphate (HMP) shunt (pentose phosphate pathway) is @ cytosolic pathway thal uses gluco: (o synthesize NADPH and ribose-5-P. NADPH is Important for fatty acid and steroid biosynthesls, maintenance of reduced luathione to protect against reactive oxygen species (ROS), and bactericidal activity in polymorphonuclear leukocytes (PMN). Ribose-5-P is required for nucleotide synthesis. Glutathione peroxidase Redused Oxidized hilathione — gltathions Gltathione Glucose reduclase | Nabe NADPH NADP NADPH clucose-6-P S-phosphogluconate Fibufose-§-P ‘Gucose 6 Sehydrogenase 03 Ribose-s-P | Nucootige synthesis Glucose-6-Phosphatase Dehydrogenase Deficioncy Episodic hemolytic enemia induced by infection and drugs (comman) or chronic hemolysis (rare); X-linked recessive; female heterozygotes have T resistance to malaria cose Prosphete ~ os 2 - ure rida Sass See canes, “hitbos ivahiene tere Prossheles spaninaaun 0, +H,0 ee) i Hemoglobin Denaturaion (ta boas) + Mgmbrane Damage ‘arava Anors) 40G Glycogen is a branched polymer of glucose, stored primary in ver and skelotal muscles, which can be mobilized during hypoglycemia diver) or muscular contraction (muscles). Synthesis of glycogen (glycogenesis) is mediated by glycogen synthase, while tls breakdown (glycogenoiysis) is caried out by glycogen phosphorylase. Branching of the glycouen polymer occurs via @ branching enzyme, which breaks an a-1,¢-bond and transfer a block of glucosyl residues to create 8 new ‘&-,6-bond. This i reversed by @ debranching enzyme. JOGENESIS AND GLYCOGENO! 5 Epiragvine cusses) @ _ Glycogen synthase -AMP iver | Skeletal Muscle MY + Mesa y é eee é 2 @ Insviin @ Insulin © chevoen @Ghses2 | © Epinepivine Synase © Glucagon land (orgranchig © Epinephrine oP -chigee Ce en @ Glycogen phosphorylase Se ve Liver ‘Skeletal Muscle a, ee @ glucagon | @ epineptvine Giucoee Giyeayis © epinephrine | © AMP e-Phosphataee| ‘taussi) @ tnsuin | © Insulin Glucose Pyruvate: Sate Branching enzyme hydrolyzes an ct, 4-bond in the growing glycogen chain, then transfers the oligosaccharide unit to @ new position and attaches it with an a-t,6-bond to creaie a branch, Glycogen synthase then ‘xtonde both branches, branching enzyme Debranching enzyme hydrolyzes the a-t, 4-bond closest to a brarich point, transfers tho ‘oligosaccharide to the end of another chain, then hydrolyzes the a-1,6-bond, releasing the single glucose remaining atthe branch pont. at,6bond ‘von Gierke disease Sever hypoglycemia tcc elds, hpatmegel, hyperipdem (¢ alucose-6-phosphatase) hyperuricemia, short stature Type I Pompe disease, ‘Cardiomegaly, muscle weakness, death by 2 years Wiysosomale-t,¢-glucosidase) “Type li: Gor dcaase: ‘ld hypoglycemia; Iver enlargement (alveogen debranching enzyme) ‘Type IM: Anderson disease Infentle hypotonia, cirhosis, death by 2 yeers |_ (branching enzyme) “Type Vi Meare olsease ‘Muscle crampsAveakness during iil phase of exorcice, possible ‘muscle aiyeodien phosphors) thabdomyalsis and myogiabinuria ‘Type VI: Hers disease ‘Mild fasting hypogiermia, bepatomegaly, chasis (hepatic yen phidsphortass) kar, medical 41Gluconeogonssis is a palitway for de novo synthesis of glucose from C3 and C4 precursors using both mitochondrial and ‘eytosolie enzymes. Occurring oniyin iver, kidney, and intestinal epithaliur. this pathwey functions to provide glucase forthe body, especially the brain and RBCS, which reture glucose for energy (Ihe brain can also use ketone bodies curing fasting concitions). Gluconeogenesis occurs during fasting, as glycogen stores become depleted. Important subsirales for gluconeogenesis are gluconaogenic amino acids (protein from muscle), lactate (rom RECS and muscle during a {from triaeylalycerol trom adipose tissues) ue . @ Pyruvate carboxylase 0 cesses oresnaase ouctnase Mitochonda, requires biotin cues 4 @ acetyl CoA [— oe ores Cytosolic; requires GTP. © Frese rececrertaies J pt © ucagon |= Poser ysis? 4g. © cartsol eatsennesr A Dian +€— ees” @ Fructose 1,6-bisphosphatase”™ arertle Gyiosole one [OAMP rr 8 F-2,6-BP (Irom PFK2) © __Glucose-6-phosphatase” In endoplasmic reticulum; only Iver “Modes neulr's inion and glucagon's stimulation ofthis enzyme “Rovere reacions of key alco kinase reactions Disease Association | Glucose-6-Phosphatase Deficiency (von Glorke disease) acc Coa tem endaten stay aos} Severe hypoglycemia, facie acidosis, hepatomegaly, hypertipidemia, hyperuricemia, short stature es ome Nik Liver pose «/-— Pyvate(2)<\— alaine ‘Apattway by vhich muscss release alanine & ‘Aagine (2) tothe liver, delivering both a gluconeogenic Beodscam Substrate (pyvat) and an amine grou for ues syntes vwasce | oubase ——> Prawn ame comin did etoasa Defniton of abbrovisiiane: PEPCK, phosphoeroipyravate carboxyinase: PFK2, phosphoftokinass 2; RG, red blood eab, TOAA‘s no transported across the membrane direcly. Instead. tis transported as malate in exchange for asperate va the malate hut (see page 38) 2 MedicalDM ceaeesunuca das) Hydrophobic Amino Acids Nonpoler, Aliphatic Side Chains ‘Aromatic Side Chains ooo exo wicdan — wiedon &) pcre Aine br me 2, wid, idan wind te] [actos ee by ona] | de ‘eo Me Po Hydrophilic Amino Acids Positively Charged R Groups Polar, UnchergedF Groups _—_-Nagativaly Charged F Groups tonnden nating aa toindon preety a) ee a a bel ye Ba o i & x i conan %| a e ect oe Aspariaes Otamate bes ad Ap ‘Gu whe lyons gare Haid te “Se he ‘aru, medical 45AMINO Acio DERIVATIVES Besides being the building blocks of proteins, amino acids are also precursors for various chemicals, such as hormones, neurotransmitters, and other small molecules. [Amino Acid Disease Association Tyrosine Thyroid hormones (Ty, T,: melanin; catecholamines {opamine, epinephvine) : ce yee mamuuatn creer, SE anal san ne Ba enalanpanaictne Serotonin’ (S-HT}; metatonin; NAD; NADP. sent aio 01: Typtphan —— Seon 60, Aronihase Adeomydalase eens etm rug} |e seems Sry Glutamate ‘paminobutyric acid (GABA) teat sone htamate > waminbut ai (GABA) ‘inne Nite oe 0) ecw siohaee Aina 0, SOOO eeu + ata wasp wade" Hlstisne Triana Histidine HsWtne deraroniase Histamine ethionine aenosynetorine (AM: maining ger) Arginine, alyeine, SAM | Creatine kp medical 4“ Albinism Tyrosine hydroxylase (Iype I) oF tyrosine \ransporter (type I) deficiency, | pigmentation of skin, eyes, and halt, T risk of skin cancer, visual defects Carcinoid Syndrome 1 Serotonin excretion fom _gastroinestinal neuroendocrine tumors (carcinoid tumors}; cutaneous fushing, ‘Venous telangiectasia, darrhea, bronchospasm, cardiac valvular lesions ‘Acute Intermittant Porphyria Uroporphysinogen-| synthase deficioncy, ‘opisodic expression, acute abdominal pain, ansiety, confusion, paranoia, ‘muscle weakness, no photosensitivity, port-wine urine in same patients, urine ‘excretion of ALA and PBG; aulosomal dominant Porphyria Cutanea Tarda Uroporphyrinogen decarboxylase deficiency; photosensitivity, skin inflammation, and bisering; cirhosis often associated Lead Poisoning Inhibits ALA dehycratase and ferrochelatase; microcyic sideroblastic ‘anemia; basophilic stipling of erythrocytes; headache, nauses, memory loss, absominal pain, diathea (lead colic), lead fines in gums, neuropathy (claw hand, wist-drop), Turing excretion Of ALA; Tx dimercaprol and EDTA, Hemolytic Crisis Jaundice due to blirubin from severe hemolysis; | hemoglobin; 7 reticulocytes; may result from: (1) GBPO deficiency hemolysis, (2) Sickle cel crisis (G) Rh disease of newborn LUDP-Glucurony! Transferas Deficiency Jaundice due to low bilirubin conjugation: may result from (1) Crigler-Najar syndromes. 2) Gilbert syndrome (3) Physiologic jaundice of newer, ‘especially premature infantsPAT ACIS) AUG EEE EUAN ILE Ani sss nq fs pon yen. hugh sae nino sas an be syed de novo (nanoeaa ws (toate Sed fo eso ctay pc Nees aio alsa sue on ees Sigyeayn dtm csc nfo cr anne sd Doane santa tts csasytonacon oe ae itp aus oc ening Coie tors the sno aos ayn odsnd 2, 0m treed oe 2s tame soernsgucten coer eos aoe) aaa Phenylarine Leucine une reine 44 See” eumyemnan owe ye ote wrote rie , ser ie : renin oe sono oo senesentt? — ppaptnuia Meloylcoloacetn 5 i Methyimalony! Com mae roe soang LY yt pence sgt Pea et ostcaeyAla——P Peg mune ——> ota frome cee — ations mao att, aie top vaooctarns—f sane! shacepemnece veresieew se SE Riwccy cur sarin ae L (eonCy TNS i seen yatta Ce Precursors for Nonessential Amino Acids “ ‘Eésontial Amino Acids* Aninnet Mathionne ‘cheats Teae | Histidine Phenylalanine Glucose — Phasphoglycerate—~ Pyruvate—> a-Ketogiutarate —> Oxaloacetate {soleucine Threonine Seine Aare canta Asatte | vee Topophen ei Catia prove Chtarinn Aspaagine | WEIE Valine Transfer of o-Amino Groups to «-Ketoglutarate “oman PVT FAL Messen ang pods of sft sn rgrany min kd mm AGH coon ago chianate Ketogenic and Ketogenic | Glucogeni lueagenie and Ketogenie Ar Guucogeie " Leucine | Phenylalanine | All others reor peecovertiean et [Sa Le rope ene eas ne-ot-g com see cross L TE Disease Association Hartnup disease Phonyiketonuria ‘Alkaptonuria | Transport protein defect with T excretion of neutal amino acids; symptoms similar o pellage; autosomal recessive Frenylalanine hydroxylase or dihydrcbiopern reductase defcioncy - buldup of phenyltanine: ‘yrosine bacames essential; musty body oder, mental retardstion, microcephaly, autosomal recessive; ‘Te L phenyalanine in dit: avoid aspartame (Nutrasweet®) Homogentisate oxidase deficiency (lor tyrosine degradation); T homogentisc acd in blood and urine (darkens when exposed to air), echronosis (dark pigment in cartilage), arthritis in adulthood: benign Homocystinuria T homocystine in urine. Classic homocystinuria, causad by a deficiency in cystathionine synthase, is associatod with dislocated lens, deep venous thrombosis, stroke, athorosclersis, mental retardation, and Marfan-lke features. Deficiency of pyridoxine, folate, or vitamin 8,, can produce a mild homooys- finemia with elevated risk of alherosclerosis (previously listed symptoms absent). Methionine synthase Qomecysteine methytransferase) deficiency is extremely rare and is assaciated with megaloblastic anemia and mental retardation Cystinuria Transport protein defect with 7 excretion of lysine, arginine, cystine, and omithine; excess cystine precipitates as kidney stones; Tx: acetazolamide Branched chain ketoacid dehydrogenase deficiency, branched-chain ketoacidosis from infancy; weight loss, lethargy, alternating hypertonialhypotonia, maple syrup odar of urine; ketasis/comaldeath ‘funtreated: Tx: valine, leucine, ioleucine in diet Neonatal ketoacidosis trom blocked degradation af valine, isoleucine, methionine, threonine, and ‘odd-carban fatty acids; Tx: these amino acids in det Propionyi-CoA carboxyiase deficiency: neonatal metabolic acidosis; hyoerammonemia; elevated propionic acid, hydroxypropionic acid, and methylitrc acid; poor feeding, vorting, lethargy, coma Mothylmalonyl.CoA mutase deficiency: symptoms similar to proplonyl CoA carboxylase deficiency, But ‘accumulating metabolites ditfr (T methylmalonic cid) afinilon of abbreviation: PLP, pyridoxal, formed frm vitamin By rape 46 ‘medicalPees ‘Amino acids transported to the liver are tanseminated to glutamate, which undergoes deamination to produce NH4* or trangamination lo meka aspartato. Both of these are used for synthes iachondl Wate Heo, + 2ATP N04" ‘catamoy crosphate Coin vanscabamojase ft ome cise (of urea in the iver for oxerton wa the urea cycle Nish Pon bcos ‘resea) | came ° etc aon © Macelyigutamatet “High protein diet > T glutamate in mitochondhia-» T N-aceiyutamate TINH," hyperanmonemia * INH," hyperemmonemia T blood glutamine 1 blood glutamine BUN BUN No increase in uracil or orotic acid Uracil and orotic acid 7 in blood and urine Cerebral edema Cerebral edema Lethargy, convulsions, coma, death Lethargy, convulsions, coma, death medical 47Lipip/ SynrHesis AND METABOLISM Fatty acids are synthesized trom excess glucose in the liver and transported to adipose tissues for storage, Fatty acid synthesis ‘occurs in the cytosol and involves the transport of acetyi-CoA from the mitochondria via the citrate shuttle, carboriation 0 ‘malonyl CoA, and linking together 2 carbons per cycle fo form lang fatty acid chains. Synthesis stops at Cy, palmitoyl-CoA, requiting 7 ATP and 14 NADPH, Metabolism of fatty acids occurs by [-oxidation, which takes place in mitochondria, and involves transport of fatty acids from the cytosol via the carnitine shuttle, then oxidative removal of 2 carbons per cycle to yield ‘11NADH, 1 FADH,, and 1 acetyl-CoA, Fatty Acid Synthesis and Oxidation (nner miocnendeia ‘nanbrane ocho oneal Cia o Promina Co fea CoA Eatboxiste a oar Mann Cok J | ray ae - waite ihe | | wane any pra ome re ave NADH ap ADH: gap en 4 co © canine (tenon FACoA teyfranateace | CoA ay ay CoA comer ‘otner | Liver ebycronenase (cary eau (tena tao) Fearne Citic Katones Carine acre spjanstonse? enray FAcamiine temo tb nny ys yw re sans ‘Soage a acigyorah asses aa ba an mnadaloy ‘sane rion pens he wo pabaye 90 cartes fhe dagrn rin sce fugit Th sure oy a3 [etenstons eraray Ver Boeduaese. "anateripanateoues 6 NADPH me HP aa. Tiiacylalycerols (tglycerides), the storage form of fatty acids, are formed primanly inthe liver and adipose tissues by attaching fatty acids to a glycerol-P. Tracylaycerels are transported from ver lo adipose as VLDL. Faty aids from the diet are transported as chylomicron. Both are digested by poproten lipase (induced by inulin) nthe capilanes of adipose and muscle. Fatty aciés may be mobilized from acygiycerals in adipose by hormone-sensiive lipase. Free fay acs are dallvered to seuss for beta exidation @ Acety-con carboxylase Ratestmiting for ftty acid synthesis; requires biotin Rateslmitng for fatty ald oxidation 2 glucagon © malonyi-Coa © paimiloy-Coa ® insuin @oirate Disease Association Myopathic CATICPT Deficiency Medium Chain Acyl-Dehydrogenase (MCAD) Deficiency Muscle achesiveakness, myoglobulinuria provoked by prolonged exercise, 1 muse’e tnacylgycerols Fasting hypoglycemia, no ketone bodies, dicarboxylic acidemia, (C8-C10 acy! camitines in bloo0, vomiting, coma, death (Continued)eee Triacylglycerol (Triglyceride) Synthesis DHAP <——— Glucose + Glucose > Giueose > DHAP ° Giycerol3-P Giycerols.P dlehycrogenase dehydrogenase © Gicoroi kinase Giyoorol «+ Giycarol-3-P AG Giycerats-P 3 FA CoA storage | omens van |. oe sro Tiglyceride (storage) Gluconeogenesis ee a a B-Oxidation » FaayAcits | ray POM con He Ketogenesis mobilization Ketone Kote ie fede fe ae ver © Giycorolo-P dehydrogenase | Glycerol kinase © Hormone-sensitive lipase ‘iach ites om ty ais Vis ayaa om Hanover doce es wr ey eornine ern Definition of abbreviations: CAT, carnitine acyltransferase (@:ka. CPT, cari palrvioy ransferasa); MCAD, longimedum chain 2j- erydrogenase; TAG, triacylglycerol, Diabetic ketoacidosis results fom overactive hormone-sensive lipase offen inthe context of stress, trauma, or infection. tru, edical «90A from beta-oxidation of fatty acids i B-hydroxybutyrata, which can be used by muscle and brain tissues. Ketosis represents a normal and advantageous response fo fastingistarvation, whereas keloacidosis is a pathologic condlion associated with diabetes and other diseases. youn a FACOA ver > Aceh cok Diabetic Ketoacidoals. 1M CoA yeas Excess ketone bodies in blood sud con associated with typo 1 diabetes Ma od se tallius not adequately managed . war with insu, ar precptated by a infection or trauma, Characterized + score by polyuria, dehydration, CNS Kase : depression and coma, sweet fnity seseenta tyme breath (acetone) ‘uae @Hrseneva) i With the prevalence of obesity and stvessil environments, kelo- Crepe i acidosis Is now becoming’ more reaches einenyyate vedere eed prevalent in ype 2 diabetics, 0. pee nS | Scab n ketoacidosis cannot Crepe Tac be assumed tobe ype 1 cnonaha Atcoholic Kotoacidosis, waste Excess Kelone bodles due fo high senoaitae 7 syeratre NADHINAD ‘rao in iver, symp- 1 et Nan toms same as above Note: Ineithertypecfketoaciosis, ‘S+hydroxybutyrate (f-hydroxybu- {yrate) i the predominant ketone scoontnl Cok body formed (not detected by the tine test). Measure 3-hycronyou- fyrate to more accurataly evalite 2 Aeay Cok v-ne-e Ce Aas Oye® eloacdosie, (offers Oey ihe si Cholesterol Is obtained from diet (about 20%) or synthesized de novo (about 80%). Synthesis occurs primarily in the liver for slorago and ble acid syrtesis, but also in adrenal cortex, ovaries, and testes fr eteroid hormone synthesis. Cholesteral may also be asterfid into cholaatorol asters by acyl-cholesterol aoy-transferase (AGAT) in cells for storage, anon @ saus.con reductase HMG-CoA roductese @ insulin glucagon ° | Smita [osm ‘Coll membranes ——> Cholesterol * Vitamin Df macology. HMG-CoA inhibitors ("Statins"), weerase, Sos scm ovaries, testes) lavasntenes aie 50 medicalDaedric ae O Mra ci chylomicrons, VLDL, LDL, and HDL. Free fall acids are transported by serum albumin, whereas neutral lipids (Wiacyglycerols and cholestorel esters) are transported by lipoproteins. Lipoproteins consist of a hydrophilic shell and a hydrophobic core and are classified by thelr density info y 9650 © Lipoprotein tipase Hydrolyzes fatty acids from {rigeyllyeerats from chylomicrons and VLDL @ insulin _Hypertidemiag | | ype Hyperglycemia | Lipoprotein lipase deficiency; T iacylgycerols and chylomicrons; orange-red eruptive xanthomas, fatty liver, acute pancreatitis, abdominal pain afer fatty meal ‘autosomal recessive ‘Type Il Hypercholesterolemia LDL receptor deficioncy; risk of atherosclerasie and CAD, xanthamas of Achilles tendon, CLASSES OF LIPOPROTEINS AND INiPORTANT APOPROTEINS ‘uberous xanthomas on elbows, xanthelasma (lipid in eyelic), ports iigivesrige from iver to tissues Ativales lipoprotein pase Uptake of remnants Upoprotein | Functions ‘Apoproteins | Functions comieal arcus, homozygotes di +20 years; autosomal daminant Chyfomierons | Transpor dietary ‘p08-48 | Secreta by epithelia cols Irglyerde and cholesterol | apaC-t Aatvatesipopotein pase z ‘rom intestine to tissues Uptake by liver =o Ehmenleey: woe 7 ‘Secreted by fiver Cholestyramine!Colestipol 1 Elimination of bile sais leads to T LDL receptor expression, leading 0.4 LDL; for hypercholesterolemia; side effect GI discomfort, Gomfibro2iiClofibrate (“Fibratos”) by liver rm Delvars cholesterol ‘po8-700 | Ustake by Iver and other In celle tissues via LOL receptor (2708-100 ceesplar), iL leks up eholestorel fom | apoe Uptake by lver| vie HDL to became LOL remnants) | Pleked up by liver MDL Picks up cholesterol ‘pont ‘Atwates LEAT to produce ‘accumulating in blood cholesterol asters vosecle Dove's holster to liver and steroidogenic tesues via scavenger recoptar (SR-B") Shutles 2p0C-Il and apt in ood 7 elimination of VLDL leads to J triylglyoerals and T HDL; for hhypercholesterolemia: side effect muscle toxilly Nicotinic Acid VLDL synthesis leads to 4 LOL; for hypercholesterolemia; side cflects: GI iitation: hyperuricemia, hyperglycemia, fushing, pruritus Definition of abbreviatirs: CAD, coronary artery disease; CETP, cholastral ester ransferpreein; HDL. high-density lipoprotein; LCAT, lecthin-cholesterol acy! trarsforaco; LDL, low-density ipoprotsin; SR-t, scavanger receptor BY; trgycerde, tiacylgyoerol, VLOL, veryow-density ipopratsin. uruaw, medical 51Tey Silay Important lipid derivatives include phospholipids, sphingoliplds, and cicosanoids (prostaglandins, thromboxanes, and leukotrienes), ‘Synthosts of Sphingollpids rae " iyscsomal Storage Disvases i Deficiency and ttt Be Disvase fecumulted Features come — Substrate la Tayssens | Uvraaniages | Gponaeromsan [A oan esate Toviegonglosse © | + Chonyred poten {urerb membranes in | roca Heotomes) « Bente yess cows Niemann-Pick | | Sphingomyelinase + Hepatosptenomagaly AR Caan) disease 1 Sphingomyelin + Microcephel ey cw (aobre Dado in + Mert aration maa essa Sooccrnea) «Foamy macophges Sane. Gaucher] J eguocaretesiace |= Tivee crcl suoypes | AR iecase oe a mon commen a T otucooerebenie |, Hoe, 1 8 mas come a &® + Bene moto al ining acute and @ bone pain % + Nevill detects (rare, types 2 and 3) + Mental retardation + Gaucher cells (enlarged macrophages vith fibrl= Elcosanoid Metabolism Skeletal deformities lary cytoplasm) Fabry Lacgalactasidase A | ~ Renal are xR disease T Ceramide trihexoside | * Telangiectasias + Angiokeratomas + Ponpheral neuropathy with pain trees Metachromatie | | arysuialase A + Ataxia AR Phaeonaipas leukodystrophy | T suifatie + Dementia ‘ * Seizuros Phosphapase Ay © (Cries Hurer J ecteiuronidase + Conse facial features | AR acide Ae ‘syndrome | garmatan sulfate» Comea clouding + Hepatosplanomegaly me / \ est Np ste ‘Oyelatiggehases Licouygenase cox (ORB 5—con, Enccoetardes Hydopeaises Hearing toss Pol, THA, _Leukotrienes ‘Hunter + Liduronate-2-sulfatase | + Both mild and severe XR voe,ece, PERE syndrome > darmaian sulfate forms ore (MPs thon + Severe sindar to Hurer but retinal degeneration instead of corel cloucing, aggressive behavior. ans death <15 years + Mig form compatible with long le Deft of abbreviations: AR, autosomal recessive COX, owooiygonass; NSAIDS, ponsteodal eni-fammatory drugs, XR, Xnked ecessve, “Common in Ashkenae Jews rar, 52 medicalberate sai Wh 2 the thermodynaic equilbrium of a chemical reaction is determined by its free energy {AG), the rate at which the reaction ‘reaches equlibrium is determined by its activation energy (4G*). Enzymes increase the rate ofa reaction by reducing the energy of activation without affecting th quilbrium constant, Michaelis-Menten Equation Lineweaver-Burk Equation Yow} KS Vax = Maximum rate of enzyme i, = substrate concentration at Vp, 1 Ke t,t VV (5) Vaae Reciprocal form of the Michaelis-Menten ‘equation to achieve a straight ine plot Ina typical enzyme-catalyzed reaction, the enzyme (E) is thought tc bind reversibly to substrate (S), fering 2 complex (ES), from which the product (P) dissociates as the. reaction proceeds, E+So€-S5E+P, where E is the enzymo, $ isthe substrate and P is the reaction product The rate of a reaction as determined by both the concentration of enzyme (E) and substrate (S) Is described by the Michaelis-Menten equation, Michaelis-Menten Plot Lineweaver-Burk Plot ‘Competitive, Reversible (offen substrate analogs that compoto {or the enzyme's binding sit) Vay 90 effoct Ke T “Compas nite Te inhibi Present 8 Noncompetitive, Reversibie (bind outside active ste but affects ‘enzyme activity, possibly allstericaly) Vas Ky no effect A rioncompsitve ltiitor We inhibitor Prasent 8 Irreversible (inactivator)Ars ese Tian (uC Biotin Pyruvate carbonviase CGluconeagenesis CCeuses (rae): excessive consumption of rv ‘Aealyl:CoA caborlase Fatty acd synthesis | 6995 (contan avidin, a btn-binding proton) Propiony-CoA carboxylase COuid-carbon fatty acs, | Alopecia (air loss), bowel itarmmation, Val, Met, He, Thr muscle pan Thiamine ()) | Pyruvate dehydrogenase POH ‘Causes: aleaholism (alcohol introres with absorption) ceKetoglutarate dehycrogena TeAcyle ‘ornicke (ataxia, nystagmus, ‘ophthaimoriega) “Transketolnse HMP shunt Korsako (confabulation, psychosis) Higroutput carte faire (wet berber) Niacin (83) Dehydrogenase Many Pellagra may also be related to deficiency ‘et siyptophan (com major eelary slap), nen which supoies@ porton of ne igen NADPH) ices Peligra: dan itt treated, death Fle acid “Taymiylato synthase Thymidine (ovine) | Causes: alcoholics and pregnancy (body THe synthesis Sores depleted in3 months) Purine synthesis enzymes Prine symtnesis Homocystinomia wth risk of dogp vein thrombosis and atherosclerosis Mogalobestic (macrooyti) anemia Deficiency in early sregnancy causes nourl tube defects infotus Gyenocobalamin | Homocysteine meihytransterase | Methionine, SAM uses amicus enema Aso ann. 8 Methyl alonyCoA mutase Odd-carbor fatty acids, | especialy with poor nation, backer oe mera vi i es Svoront "ral fur cet te terminal feum secandary to Crom disease, chrono pancreatis, and, arly, vegena, or infection wth Diploboinam tum Megalobastc (macrooyie) anemia Progressive pespheral neuropathy Pytidoxin (8) | Aminotransterases(ransa Protein catabolism ‘Causes: isoniaid therapy PUP AST (SGOT), ALT (SGPT) S-Aminolevunate synthase Home syathesis Siderobtastic aneria Chelosis o stomatitis (racking or salng oF lip Borders and comers ofthe mouth) Convisions Fibotavin (©) | Dehydrogenases Mary ‘Comneal neovascularization FADUH,) | Chetosis or stomatitis (racking or scaling of lp borders and comers ofthe mouth) Magenia-colore tongue ‘Ascorbate (C) | Prot and iyey hydronyases Collagen synthesis ‘Gauees: dint dafeient in crus tats and Dopamine Shysronfase Catecholanine synthesis. | _ fen vogstabos ‘Absorption af iron GI | SEU: peor wound healing, easy bruising tract (Poneliculer hemathegs), blessing gums, increased bleeding tina, painful glosita, | anemia Pontethenic acd | Fatly acd synthase Fart acid metaboism | Rare cok Fatty acyl CoA symetase Pyruvate cehysrogenase POH e-Kotogitarale dehydrogenase | TCAeHCIe Deiintion of abbreviations: ALT, alanine aminotransferase; AST, wspertate aminotransferase; Gok, coenzyme A; PAD(A), avn adenine dinucleotide, HMP, hexose monophospnate shunt, NAD(H};nizatnamide adenine diucieotide, NADP(H), nieaipamige adenine dinucioatise Phogphate; PDH, pyruvate dahydrogenase: PLP, pyridoxal phosphate, SAM, S-aderosyimethiorine; TCA, bicarboxylic aid cycle; THF, {elranyarofoate. apca, medical1D (cholecaicieroi) In response io hypocaicemia, helps normalize serum ‘alolum levels Rickets (in childhood): skeletal abnormalities {especially legs), muscle weakness Aer epiphysial fusion: osteomalacia ‘A (earotene) Retinoic acid and retinol act as growin regulators, | Night blindness, motapasia of comeal ‘especialy in epithelium epithelium, dy eyes, bronchitis, pneumonia, Retinal is important in rod and cone cells for vision _| flicular hyperkeratosis K Cerboxylation of gulamic acid residues in many Ga- | Easy busin, Bleeding ‘ining proteins, importantly coagulation fociors Ki, VI, | increased prothrombin tine 1, and X, a6 well as proteins C and § Aasoctted win et malabeorpen, longer ‘anibiotc Iherapy, breast-fed nevboms, infants of mothars who took anticonvusants ‘uring pregnancy (wtocophercl) | Antxidantin the iid phase; protects membrane | Hemelyss, neurologic problams, ais lipids rom peroxidation and helps prevent oxidation of LDL particles thought to be involved in atherosclerotic plaque formation pigmentosa capi, 55Molecular Biology, Genetics, and Cell Biology Nude Aa Srucre se Nec Ai yrthes ond Sahage 5-60 DNA Rephation a DNA pat a “Tarscipon and RNA Processing 8 Protein Farlation st Peat Yarlonal Mediators 6 Colegen Sys 66 fecombirart DNA, 61-68 enetic Testing. oe 69 Pate of Irhertance, 0 Sle Gene Dsades, 7 (Gomosoml Abnormalities n (ther Chvamosal Abnormalities 1 Popdaton Genetics. 8 SubctarO gna, cocci OT Pasma Membrane 8 0 20 cal oye at Cel Siang oe Eye Kinetics 4NucLei¢ Acip STRUCTURE Wucieic acids, including DNA and RNA, are assembied from nucleotides, which contain a five-carbon suger, a nitrogenous base, and phosphate. The sugar may be ribose (RNA) or deoxyribose (DNA). The base can be a purine {adenine or ‘quanine) or pyrimidine (cytosine, uracil, thymidine). Phosphate groups link the 3° carbon of one sugar to the 5’ carbon of the next, forming phosphate bonds. Base sequences are conventionally writen in a 5! ~» 3’ direction. Nucleotides lacking phosphate groups are called nucleosides. In eukaryotes, RNA is generally single-stranded, while DNA is generally double- stranded in an antiparallel orientation, with two hydrogen bonds between base pairs A and T and three between G and C. Nuclear DNA forms a double-helix, which undergaes supercoiling via topoisomerase activity, and is generaly associated with histones and other proteins to form nucleesemes, the basic packaging unit of chromatin. Tho B-ONADourle Hal | _Nomenei Base | Nucleoside | Nuclootide Adenine | Adenosine | Adenyiic ‘acid Adenosine (aM) Guanine | Guanosine | Guanylc ‘ac Gusnosine ‘oanophosphate (GMP Gytosine | cytidine Cytidyic acid cytidine ‘monophosphate (em) urecl | Uridine Uric cio Utne ‘monophosphate (uMP) 200m os Euchromatin Heterochromatin Loosely packed Tightly packed ‘Transciplionally active | Transcripllonaly inactive SGicalRie cueiau seein Nucleotides for DNA and RNA synthesis can be generated by de novo synthesis or salvage pathways, both of which require PRPP generated from sbose-S-phosphale derived ftom the HMP shunl. De novo synthesis occurs mainiy in the liver and generates new purine and pyrimidine bases from precursors. In contrast, salvage pathways reuse preformed bases derived from nucleotides during normal RNA tumover er releases from dying colls or transported from the liver. Ribonucleaides are converted to deoryribonucleotides for DNA synthesic by ribonucleotide reductase. Excretion of purine bases occurs in the form of uric acid from the kidneys. De Novo Purine Synthesis De Novo Pyrimidine Synthesis © oxy ret ‘see iit caeney ot ae ON ress eee aa aoe. i 3s Caen Borer ta. norenegganiae Oreginonne st Awe on owe awe wenenaee eae Poets @ PRPP amidinotransferase Grigio oman Paine Rig Gage othona n Pyare Rng c0-—6 Glutamine Glutamine Definition of abbreviations: AMP, adenosine menophosphale, dTWP, deoxylhymidine manophosphala; IMP, Inasine morophosphate, UDP, deoxyuridine diphosphate; CTP, cytosine triphosphate; THF, tatrahyérofoate (Continued) arcaw, medical s9‘Adonosine Deaminase Deficlency ‘SCID (no B- oF Tcel function) Multiple infections in children ‘Aulosomal recessive Gout Leseh-tiyhan Syndrome + HGPRT deficiency + Mental retardation (nid) spastic cerebral palsy + Seltmatltion + Hyperurioemia + linked recessive Tx: enzyme replacement, bone marrow transplant 1 production or & excrotion of uric acid by kidneys DNA, RNA, and high-energy compounds (GTP, ATP) | | IMP —> Asp ewe ‘Adenosine Guanosine | HGPRT. J deanimase | (salvage) HGPRT (Galvage)| —_Inosine Guanine Hypoxanthine Xanthine | Xanthine oxicase (excretion) Uric acid Purine Analogs. Allopurinat + Inhibits PREP ‘aminotransferase + Treatment of gout + Inhibits xanthine oxidaso S-mercaptopuning: 8-azaguanine + Innbits PRPP amidino- transferase + Antineoplastic Pyrimidine Analogs + Antineoplastic, Folle Acid Analogs ‘Methotrexate; aminopterio * Inhibit eukaryotic DHFR + Antineoplastic Trimethoprim * Inibit bacterial OHFR: + Antibacterial Pyrimethomine Inte protozoal DHER tiprotozoal Hydroxyures * Inhibits ribonucleotide reductase Antineoplastic + Treatment of sick cell anemia ‘Dafinion of abbroviotions: DHFR, dinyaroolata reductase, HGPRT, nypoxaniNne-gu ‘hosphoribosy pyrophosphate vansterese, NSAID, nonsteroidal art-infammalory drug; PRPP, phosphoribosyipylophosphale; THF, tttahyarefolate; SCID, severe combined Immunodeficiency disorder. 0 so medicalBsagueruen DNA replication involves the synthesis of new DNA molecules in a 5 > 3' direction by DNA polymerase using the double-stranded DNA template. One strand (leading strand) is made continuously, while the other (lagging strand) is synthesized in segments. Prokaryotie chromosomes are closed, double-stranded circular DNA molecules with a single origin of replication that separate into two replication forks moving away in oppasite directions. Eukaryotic chromosomes are double-stranded and linear with multiple origins of replication. DNA Replication by a Semiconservative, Regul ditctional Mechanism ou = Prokaryote Recognizing | dna Pretajtes evraryohe replication Ot ot Repeat ‘nate Qe of Repheaon erin = Unwinding | Hetcase Helicase OTo os RNAprimer | Primase Primase | synthesis, Leading strand | DNA pat I DNA pol 5 synthesis w& ‘ce Taapgeree [Bupa vos ‘epuied Beng Vise saesis RNA primer | ONA pol (6 3° | Unknown removal ‘excnuclease) Events at the Replication Fork Replacing RNA | DNA pot Unknown with ONA Pee Joining of DNA ligase (use| ONAIgase =P adhe Okazaki NAD) (use ATP) fragments Removing NA topo (OWA | DNA topo t positive ‘yrese) supercolls ahead of replication fork Telomere Not required Telomerase synthesis agang cant Pyrimidine Analogs: Oyfosine arabinoside * Incorporation stops chain elongation + Antineoplastic Detntion of abbreviations: DNA, deoxyribonucteic acid; DNA pol, DNA polymers DNA topo, DNA topoisomerase; RNA, rtonucile cid, SSB, single-stranded DNA-binding protein, medical 6ao DNA sequence and structure may be altered either during replication or by exposure to chomicals or radiation. Mutations include point mutations such as insertion or deletion of bases, oF substitution of one base wit another Substitution mutations in the third position of a codon (wobble position) are usually benign because several codons cade for the same amino acid, Other types of mitations include (1) large segment deletions (e.g, unequal crossover during meiosis), (2) mutations of 5” or 2 splice sites, oF (3) {riplet repeat expansion, which can lead to a longer, more unstable protein product (e.g., Huntington disease), | Recognitions Repair Damage ‘Cause | Excision Enzyme Enzymes Tiymine mers | UVradialon | Excision ndonucienso | DNA 6) (Gefen in xeroderma polymerase RTO GE of SC OAT Pigmetoaim) DNAligate : cysine rac ayeoslase DNA sr oon) 8u ‘Jeumnation(@,) | ehomene” | Ab anionioeace pebmerase | Stent | Nechange | Sub ONA igs ounaion or) Spntaneoua’ | AP endonilease BNA mene anor |e ‘pyrimidnaton | heal polymerase () DNA ligase Nonsense | Early stop ‘Sub or - eden Iie Wismatches | ONArepicalon | Amutaion on one of wo | ONA as8 (Gy) one genes, shiver ute, | polmerase FrameaniTyasesang 7] mabe ince cobcive part | on igose it | Waeaicg || na ONA mismatches, ruth soanstaare ina condition known as hereditary nonpolyposis colorectal cancet—HNPCC. DNA Repair Detects Xeroderma Pigmentosum (dotoct in nucleotide excision-repair) Thyminw owe Tnson stp Niki by Uvepecte ondonucease Pomel axsodtoshesse Se Tm, nro DNA polymerase >>| sateen Ton. J {aslon by DNA oe + Exireme UV sensitivity + Excessive frecking + Muliple skin cancers + Gomes ulcerations + Autosomal recessive Ataxia Telanglectasia (defect in ATM gene product, a member of PIS kinase family involved in mitogenic signal transduction, detection of DNA damage, and cell cycle conto!) + Sensitivity to lonizing radiation + Degenerative ataxia + Dilated blood vessels * Chromosomal aberrations + Lymphamas + Autosomal recessive HNPce (asfect in mismatch repair; usually /nkiSH2 oF DMLHT gona) + Colorectal cancer + % occur in right colon + Autosomal dominant Dofntion of abbrovistions: AA, anno acié; HNPCC, hereditary nonpalyposis colorectal canoer; Ins/Dal, Inger or deletion; Sub, substitutionTRANSCRIPTION AND RNA ProcessiNG Transcription invalves the synthesis of an RNA in a 5° ~ 3° direction by an RNA polymerase using DNA as a template. An important class of RNA is messenger RNA (mRNA), Initiation of transcription accurs from a promoter region, which is the binding si polymerase, and stops al a termination signal. In prokaryotes, a single mRNA transcript can encode severel genes (polycistronic), ‘and no RNA processing is required, allowing transcription and translation to proceed simultaneously. In eukaryotes, all mRNAS are but often include coding segments (exons) interrupted by noncoding regions (Intrans). Eukaryotic mRNAS must therefore undergo extensive processing, including @ 5’ cap, a tall, and splicing of introns. Ribosomal RNA (RNA) and transfer RNA (RNA) are also produced by transcription, of RNA Prokaryotie Transcription iE "Properties i en Prokaryote Eukaryote we 98 cea eT | enw eglons | Maybe potycovone | Aways ou BT eT Continuous coding | manocisvonic . ae * Exons ane s oer mi invons RNA ore enzyme: a26fv | RNA pol : RNA oe polymerase RNA ol i mRNA, a sexe snRNA TE an ws RNA pol RNA, NB cman 1G ue NA po initiation Promoter (10) | Promoter (-25) TATAAT and {-35) TATA and (-70) Sequence, sigma” | CAAT, anerpton initaton subunit | factre (THD) bind promt Termination | Stem loop and UUUU | Not wel ar stem loop and mo | characterized SS Roemer gce | yum = | factor eo va ale Postpracessing | None 5’ cap (7-MeG) = vot 23 tal (polyA) mre intron splicing of nn a ee ee 7 aoe =< We mRNA Messenger RNA carias sequence info fom | DNA to ribosomes to bo translated meet rRNA Ribosomal RNA isn component of ribosomes ¥ ee metas ‘RNA Transfar RNA corres amino acids to . et ribosomes for potan synthesis, cbs SRE? snRNA Small lear RNA plays role in RNA ah processing _ Regulation of Gene Expression. Transcription | Transcription factors bound to enhancer ination or silencer DNA renion fect transcription ee Slicing Ateralve splicing of primary wanscit veld — variants of protein products mRNA Various RNA-binding proteins determine snoaocom epradation | stabity of mNA Defntion of abbrevions: hnRNA, heterogenous nudeer RNA; 7-MeG, 7-methylquanosine; RNA pol, RNA polymerase; UTR, untranslated region. ariee medical «3Protein synthesis begins rom an ination cocon (AU attached at the otter end for covalent linkage to the growing polypepide chal mRNA, forming a ealyribosome, or palysome ‘methicnine) and ends at a stop codon (UAA, UGA, or YAG). Elongation involves transfer RNAS (IRNA), which have an anicedon region at one end to recegnize the codon en the mRNA and a amino acid ‘Several riboscmes can simultaneously transcribe an Genetic Code Properties eee Prokaryote | Eukaryote [SB LSBs EE] | rmowomes | sag 0s = | 408 + Ra ea ee ms as BE Re. ee ESL. ASPB EAI |iia Ela) 2 Vaniation | os binds | 40s i fo festino | associres Ree Bagemo | wis" cap on a “| sequence MRNA; Met ese ie [aslo | Protsn released a sop codon : Eee) aaah tends 0 2 egeenen tontons 2 hott norms Pay “ footie peer | *jamecer agen Gases a Bete = urgent pen Eon ra eee TERURIATIN consng en ransom ior rN tsi: sree eono BP NS Formation of Aminoaey/4RNA Potyribosome Pharmacology Tekacyinos ww eomedicen —ncdidann Jot | tetmcyin, doxeetn mioeytne) wy ‘ S | "prensa ofamtecon A bec + For Chiamyaia, Mycopiasma, 4. pylon, Rickettsia, Sruvele, Vibrio, and acne + Propiyaxss in chronic branche, + Baclriosiac + Photolowey, Gl datase, tooth eiscaoration, Lone giow in arteren Linezoid + Blocks intaton complex formation + For VRSA, VRE, crupresistart pnaumococct + Headache, Gl disress Aminoglycosides (otroptamycin, gentamicin, neomycin) * Cause miseadtng at inition + Accumilates ntracelllar vis O,-dependont Uptake; anaerobes are resistant + For gram © rods, enterococci + Bactencidal + Noghratoiey ooroxaty Macrolides (exytiromyan, dasthroniycin, aihromyein) ‘interere wth vensiacetion + For gram & cote Chiariyta, Mycoptesina, Ureaplesma, Legionelia, Campylobacter + Bacteriostatc + Gl sires, intiits Paso, audlry dysfunction athigh doses tindamyein + Sotetores with transleeat rs + For gram © 0ce, B fags + Pseidememarancis c Chloramphenicol + Inhiotsrbosornal pootiey| transferase «For Selmenetia, fragile, Rcketoi, ane bacteial meninalis (used as backup) + Bacittostatc + Bone marrow suppression: aplastic anemia, ‘ray baby’ sypsrome (neonates), onli nouns (etitaren) Definite of abbrevistions: AK, arine ate: EF, elongation facie 2; ls, formiatNonine; Mt, mativanna: URE, vancomyehnresistant eile peel: VRSA, vancomycin reaistant Sionyincoccus meus, ary, 64 medicalWelvisieauess ‘Whereas cytoplasmic proteins are translated on free cytoplasmic ribosomes, secreted proteins, membrane proteins, lysosomal enzymes have an N-terminal hyérophobic signsl sequence and aro vanslated on ribosomes associated with the rough endoplasmic reticulum (RER). Aller translation, proteins acquire more complex structures by being folded withthe help of molecular chaperones. Misfolded proteins are targeted for destruction by ubiquitin and digested in cytoplasmic proth-digesing complexes called proteasomes, Go. and Postranslational Covalont Modifications j Protein Structure Glycosylation Addition of oligosaccharides Primary _| Amino acid sequence Phosphorylation Addition of phosphate groups by protein kinases | Secondary | a-Helix or B-shests ‘yearboxylation Creation of Ca binding sites Tertiary | Higher order 3D structure (itamin K dependent) Prenylation ‘Adcition of famesyi/gerany) lipid groups to ‘Quaternary | Multiple subunits memrane proteins Mannose phosphorylation | Addition of phosphates onto mannose residues 10 target protein to lysosomes 5 . Scena anslaon et Srna ‘meyers sonia we ‘rye Sere! signal Seavence causes essa sisceomate niece arin S| Foevenon a z ‘Signa Peptiteperoton “ne Sig Seauonca ‘Tarleton Continue Steosaon in Em (Chrsnecainaoah racer Morwanaor «OO, Call Diewase (@efect in mannose phosphorylation, causing lysosomal enzyme releass into extracellular space) tures, gingiva! hyperplasia, macroglossia ‘2bnormalites, joint immobitty, club foot, claw+hand, scoliosis + Psychomotor and growl retardation Cardiorespiratory failure + Death i frst deceds + 10-20-Fls increase in vsosornal enzyme activity in serum apa, medical 65Collagen is a structural protsin composed of a ‘ple helix of amino acid chains containing @ repeating tripeptide Giy-X-V-Gly-X-Y, where the unique amino acids hydroxyproline and hydrexylysine are frequently found in the X positon, Hydroxylation of proline and ysine requires ascorbate (vitamin C), deficiency of which leads to scurvy. ‘Synthesis of Coltagan Disease Association mre oro Gran ws “Hpatepnatic Sal Suan ernval of Signal Sequence ty Sigal Peplteee yoyo of etc SET anc waned on on on yeceltion Seletee Hitorsines tit a on [ower Propeples be dapat (i229 [es it te Ses yay Gide Cut) | sess” a a ‘Scurvy {reduced hydroxylation duo to ascorbstelvtamin © dafcioney) + Petechine, ecchymoses + Loose teeth, bleeding gums. + Poor wound healing + Poor tone development Osteogenesis imperfecta (collagen yene mutations) + Skeletal deformities + Fractures + Blue sclera Ehlers-Danlos Syndrome (coflegen and lysine hydroxyiase ‘gene mutations + Hyperextensile, agile skin + Hypetctil joins, dislocations + farizose veins, ecchymases Menkes Disease (dofciant cross-tnking secondary 10 ‘copper dafiaency) + Depigmentad (sleei) heir + Arterial lortuosily,ruplure + Geretital degeneration + Osteoporosis, anemiatoe >) with specifc restriction endonucleases, and Incorporation into humans (gene therapy) or ther animals (transgenic animals). Recombinant DNA technology allows DNA fragments to be copied, manipulated, and analyzed in vito. Eukaryotic DNA ‘fragments may be genomic BNA containing both introns and exons, or complementary DNA (cDNA), which is reverse- transcribed from mRNA and contains exons only. DNA fragments may be amplifed by polymerase chain reaction (PCR), cut 3d into @ DNA vector. These vectors can then be used for further manioulation ‘or amplification of the DNA to produce genomic DNA or cDNA (expression) libraries, fo generate recombinant proteins, or for __Formation ofa Recombinant Plasmid Polymerase Chain Reaction wt ouaat set wh ar PFS orcearees SR iia roe ~~ crt een + Ampliies large amounts of DNA from even just one DNA ‘molecule + Used for recombinent ONA ‘manipulation, genetic testing, cr disease screening + Can be used to make CDNA {rom mRNA with reverse transcriptase IRTPCR) EM [ peatiooee ‘eX TPs and Tag Poynrase Paymoreaton st 72°6 (Continued) kara, medical 67Screening a DNA Library Restriction Endonucleases os ee Qa Feplcn of grows feean Be ea © yee taster, anus Ohh and 08 Sm Anessa gee: vrata ators lyse tector att ante prose mace aveogern + Recognizes palindromes in dsDNA and Cis, leaving sicky or blunt ends + Used to make restriction maps of DNA or to preduce fragments for maniguiation Sooo egs6 Tg 1 pate s-908 + 8-009 soocegce * Sea 3 Pek pose coon Pic posite sieny ‘ont engl ae Tortoigia! pte Incorporation of Cloned DNA DNA Vectors [eee A apes rag Gee Toy (Soa ] Trego Anais (Gaon Li) rant MK 5 Porlized OVA k Micre-nject Cloned gene inseriento DNA ot seleaed somal eats Bene ner passed ts aforng one DNA New gone incorporated Vector usa s boc conse gone ‘no gam ine CNA Ino nest ONInude Exar <= AD 4D 4D SQ 3GID (eevee combined imino: slleieny,mlorovain raptor gore + Gyate fost: GA gene OFfepang ee wansgenie Now gene raartod s @ ranagone Desian arial made foc humer sleoase hie way Circular, seltseplicating DNA to cary and amply DNA fragments in bacieria or yoast 100-12 kb | Plasmid Bacterial: resticton sites, roplication origin, selection marker (eg, ztllase resistance) 10-25 kb | Phage Packaging vitus that infects bacteria: e.g. lamoda (2) Upto45ko | Cosmid Plasmids wit A cloning sites Upto 104» | BAC, YAC Bacterial or yeast arificil chromosomas: Defiion of abbreviation: dsDNA, doubve-cirnded DNA.The presence of specific DNA, RNA, and proteins can be identified by fist separating these molecules by gel electrophoresis, transferring fo a membrane by blotting, and finally detecting wth radioactive nucleic acd probes (for DNA and RNA) or antibodies (for proteins). Direct detection in alls o tissues can alse be perforined using similar tools lo identity MRNA (in situ hybridization) OF proteins (Immunestaining). \n viro detection of proteias can also be achieved by enzymeslinked immunosorbent assay (ELISA). Using these methods of detaction, diversity between individuals or genetic mutations manifested by diferent restriction ‘endonuclease sites (restriction fragment ength polymorphisms [RFLP)) or expansion of highly repeliive sequences (e.g. satellites, rminisatalitas, and microsatelites) may be emplayed for genotic tasting “BNA RNA Protein Repeated Unit | Longth of Repeat Separation Gel electrophoresis Satellites 20-475 bp | int Mb Blotting | Southern | Northern Westen Minisatetites | 20-70 bp Up to 20K (robe) | CP-DNA) | (%P-0NA) | (oF antibody) ‘Other — Insts | Immunostaining or | Microsatatites | 2-4 bp <180 bp detection hybridization ELISA TTS Gal eae (Seaton ign RR) Paternity Testing (PCR: Miorosatuilite) | Mail restriction digest of patient sample, folowed by Southern blattng using a probe agains! f-giobin gene, allows identification of either tho normal or sickle allele. PCR amplification of microsalelile sequences can be used to match the banding pattem to each parent. The child should snare one sllele wilh each parent Met este Map othe cain ne 3 : 8 ct * igi B23 romain 5 233 3 sist) — Fagrat S28 = Ssliawestoatrt | fod | ssn - Cystic Fibrosis (PCR; ASO Dot Biot) ~HiIV.etection (ELISA and Western Biot) The most common GF mutation, AFSOB, can be detected by ‘comparing PCR product sizes by gel electrophoresis or hybridization with allele-specific oligonucleotide (ASO) probes on a dot blot (a simplified form of Southern bial Serum antibodies to HIV ace frst detected by ELISA and then confirmed by Western bit Seno Sow Satire aruag medical «2‘Autosomal Dominant + Alfacted individuals have an affected | + parent + Either sex affect + Variable to ate onset may be delayed to adutnoed) + Often eneade structural proteins he een eae + Familia! hypercholesterolemia + Huntington disease + Nourofibromatosis + Marfan syndrome ‘von Hippel-Lindau disease ‘Autcsomal Recessive Affected individuals usually have unaffected (carier} parents Either sex affected Early uniform onset nfaneyichitdhood) ‘Often encode catalyie proteins ‘Sickle cell anemia Cystic fibrosis, Phenylketonuria (PKU) Kartagoner syndrome tye a Oo on Ota 0 wm iment pe coon a n° Sv © sxiuny ob oe 1 sneinoan — Gy trea we X-Linked Dominant + Affected individuais have 2° affected | + parent Fithor sex afte : Ne male-to-mele transmission : Females often have more mild and | + variable syenptoms tian males eS + Fragile X syndrome + Hypophosphatemic rickets, X-Linked Recessive Aleced individuals usually have unaffected (carrier) parents Usually atfoct males only No male-to-male transmission Fomale carriors sometimes show milé symptoms Gro “0 oO ob ‘Duchenne muscular dystrophy Lesch-Nyhan syndrome GEPD deficiency Homophilia A and B ‘Mitochondrial Inheritance + Inherited maternally bocause only mother contributes mitochondria + Either sex atfected + Usually neuropathies and myopathies because brain and muscle are Fighly dependent on oxidatve phosprovyation + Leber hereditary optic neuropathy + MELAS: mitochondrial ‘encephalomyapathy, lactic acidosis, and stioke-tke episodes + Myoclonic epilepsy with ragged rec muscle fiber Decision Tree for Datermining Mode of Inheritance ‘aia Cassie) (Garp omcine anc) no ‘Ente Domina (Greaene or | | ox mora anne axcpos Gerwetons| [ak ad agi enter vse Coty ‘asise ann Bonnin of abbroviaton: GEPD, gluccea-6-phosphats dehydrogenase. “Note: If wanemission eccurs only through affectes mothers and nover rough acted sons, the pedigree Is key to tflect mtachendal inheritance,Bice acshi a Scena Neurofibromatosis (NF) Type 1 {von Recklinghausen Disease) von Hippel-Lindau Disease Features [mutation in NF umorsuppressor gene on ‘chromosome 17) + Mutiple neuroftbromas + Café-au-tit spats (pigmented skin lesions) + Lisch nodules (pigmented iis hamartomas) + Increased risk of meningiomas and pheochromocytoma + 90% of NF cat * Autosomal dominant (mutation in tumor-suppressor gene on ‘chromosome 3) + Hemangioblastomas in CNS and retina + Renal call carcinoma + Cysts in internal organs + Autosomal dominant Neurofibromatosis (NF) Type 2 (Bilateral Acoustic Neurofibromatosis) Cystic Fibrosis (mutation in NF2 turar-supprossor gene on ‘chromosome 22) + Bilateral acoustic nouromas + Neurofibromas and café-atrait spats + Increased risk of meningiomas and pheochromocytoma + 10% of NF cases * Autosomal dominant Marfan Syndrome (mutation of fibitin gene on chromosome 16) + Skeletal abnormalities (al build with hyperextensible joins) + Subluxation of fens + Cardiovascular efects (cystic medial necrosis, dissecting aortic aneurysm, valvular insufficiency) + Autosomal dominant (mutation in CFTR chloride channel ‘gen on chromosome, leading to thick secretion of mucus plugs) + Recurrent pulmonary infections (@ aonigiresa and S. aur0Us) + Pneumonia, bronchitis, bronchiectasis + Pancteate insuffeency; steatorhea + Fateabbie ulamin defiency Malo inert Bilary ceria Meconium ileus Most common mutation: AFSOB Dx? NaClin sweat: PGR and ASO probes + Tx: Aeacelycyatein, respiratory therapy, ery replacement, vain ‘supplement + Autosomal recessive Variable expression— C,,) Phospholipid exchange reactions Bile acid synthesis wana, medical 7ty fg bs Lp ait mera aie The plasina membrane ofa vel ea bilayer of Kids ad protein. The Ups etude phospholipids, unesteled cholastarl, re Cvoalos ane eo ampnipathie (polar head fo nara! wid aqueuce enon, and opp el tantra hy the tayo intro, Protos may act as adhoston molecules, receptors, ransprlas, channel, or enzymes, Protein embedded inthe lover are Integral protein, whereas ‘rose loose associated uh the momnbrane are peripheral protins. gener, Nealycosyiation of rele and ips eosociteo wih ocaton on the extol urocs, wherece Remyrstoyiation, pronytatian, and paliloytation of proteins are associated i ocaton ne eolasis face ot he plana membrane Structure of Biologie Membranes Peripheral integral otein protain {N-glycosylation) Extravetular LOGQOOUCOEOOOG-Husreriic ens ¢ Phosphoipid Vastepds 2 ails LHydrophobic en] ""°SPn' 1000090000900000 Perper protsin (emytstoyation prenjation, panty) ‘Types of integral Membrane Proteins Exracotular side Tel pel ype Iniracotular sida Types of Transport ‘Simple Ditusion Facitated Bifusion ‘ative Transport ~ Movornnt of hight pareable ~ Passage of poo permeable ~ Movement of molecules fom a region moles toma regan ot higher to |” molec Fron a region of igher io |” oflowerto higher coneertvaton over eoneantion (ower eoncenvaton va carrer sith) energy expemre a AT? + 2g, O, CO, + 2g., glucose transporter hydrolysis, or 2) cotransport using ® cher mows cremea recon: + e.g. 1) Naik” pump, Ca?-ATPase + bs 2) Natu symparer | B variaw, medical‘The cytoskelaton consists of # supportive network of tubules and ‘llarionts in the cytoplasm of eukaryotlo ods. 1 & dynamic structure responsibie for cellar movement, changes in cell shape, and the contraction of muscle cells. Itaiso provides the ‘machinery for intracellular movement of organolios. The cytoskeleton is composed of three types of supgorive structures: ‘microfubules!, intermediate filaments, and microfilaments. Disease Association chromosomes in mitosis 6 meiosis + Intracellular wansport via motor proteins + Cllary and flagellar mrotlity Microtubules” Intormediste Filaments | Microflaments Tubulin (holiow + Keratin (apithetium) Actin {double-stranded tinal polymer of | « vimentin ranopithela) | Polya bested in tubulin dimers) + Neurofitament (neurons) | Helea! pattern) Funetion + Movement of Siructure + Swucwral + Muscle contraction Via interaction wits myosin sheath Bridge a eo Chodiak-Higashi Syndrome (defect in microtubule peiymerization in Teukooy'20) + Recurrant pyogenic infections ef respiratory tract and skin + Paria alsn'sm + Photophobia, nystagmus, peripherat neuropathy, motor dysfunction, seizuras + Presents early in chit Kartagenor Syndrome proteins, such as dynein arms) + Chronic cough, rhinitis, and sinusitis + Situs inversus + Fatigue and headaches: 1+ Male inferty tom immoilo spermatozoa + Autosernal cacassive Pharmacology ‘Motor Proteins Kinesins for 8 -> @ anteroarade direction Dyneins for © -» © retrograde direction Colchicine + Inhibits tubulin polymerization + Used for gout ‘VineristinalVinblastine + Jnhibits tubulin polymeriention + Antineoplastis Taxol + Promotes tubulin polymerization + Antineoplastic “Miorotubil6s are polarized structures wih assembiydlsassembiy ceouTing al tha end, which are anented toward be oalls penphory. medical 72‘Aoal must physleal interac via cl aurface molocuie wh sextenal environment. whether ibs the extracellar matic or base ‘ment membrane. The basement membrane isa sheath structure underlying virtually all epitrela, which consists of basal laming (mado of ype VI collagen, glycoproteins [29.,arinin], and proteoglycans (e.g. heparin sulfate), and reticular lamina {composed ‘af eaticula fibers). Cel june'iens anchor celle te each other, seal boundaries between cells, and form channe's far direct transport and eemmuricalion between cels, The three typas of junctional complexes include anchoring, tight, 2% gap junctions, Gell Junctions: Extracellular Matix adjacent epitheliat coll, forning an “aanesion bel” + Desmosome (macula adherens}— [ustaposition of wa disk-shaped plaques trom adjacent calls, with IF radiating away from the plaques: hemidesmmosomes anchor calls to the fexeaceliar matrix cal ace | etesme menting r Tt iunedon resi Inert DDeerasome| fers) J] Gap neons coin eat Memicesrresame ‘ ‘Anchoring Tight Junctions Gap Junetions Junctions + Adherens Tight junction fzonuln Gap junctions Junction (zonvla | eceludons)tislen of ‘tact passage for smal adherens} | apposed ee! membranes | partces and Ions between Bande funtion {ells via connexon char near apical region proteins for attachment 0 Proteoglycans. + 90-95% carbohydrate, 510% provein + Forms hydrated gol for embedding fxous proteins + Provides shock absorstion and haan Collagen + Trhie hel of polweptide chains fh in glycine and proline allagans Il: forous fom fo stucturs + Collagen Iv: ehasto mestwork pestle ta basal lamina Etastin + Grossinkew fears rn in glycing ane prene + Provides clasts to tissues (2.6, lungs and large arteries} Fibronectin + Large, forous proisin with dsulfde crosslinks + Prouides adhesion between cols and extracellular matrix Laminin + Three polypentise caine in shape ‘of 3 cross and connocted by sioulide bonus ‘+ Major alyooprotein in basal lamina + Provides adnasion botwoon tells and extaceliviar matrix Disease Association Funetion For structural integrity iarge sheets of issues (4, providing lanai strength of epithelial tissues), adhesion bolt also alles epthetal tissue contractions Provides a tight seal to prevent fd foak between. ‘Allows eect intorceluiar ‘communications (2.9, allowing ‘ors to 6998 for ‘synchronous fring of cardiac pacemaker calls) Pemphigus Vulgaris (autoontbouies agains! desmosemat potoins in shin cots) + Painful Baceid bullae (bisters) in ‘oroahary and skin tat rupiure cally + Postnfiammstory hyporpigmentation + Treatment coricasteroide Bullous Pemphigoid (auioantoodies against basement. membrane hemidesmesoml proteins} + Widespresd blistering with pruritus + Less severe than pemphigus ‘wags + Rarely aflects oral mucosa Can be drug induced (eg, riddle aged oF eldery patent an matiple medications) + Trealmant cortcastorods Datiniion oT abbreviations: ara, medical Fr nieimedile fiement,‘The coll cycle consists of the mitosis phase (M) the prosynthetic gap (G.), the DNA synthesis phase (8), and the postsynthatlc {gap (G,), Mitosis is the shortest phase, consisting of prophase, metaphase, anaphase, ard telophase. Both G, and G, phases fre varable n duration, with most cells sperding much of their ime in a stable, nondlviding G, phase, Cells in G, have fwice the ‘amaunt cf INA as those in G, S phase {DNA synthesis) Ne Phases of Mitosis Prophase + Chromosomes ceil + Nuclear envelope disappears + Spindle apparans torene Metaphase S Chromosomes align Chromatids separate Regulators of the Cell Cycie + Chromosomes uncol Cyctins | Gyetinfovels sss ard fa with stages of ce cyte. + Nuctoae envelope reappears CoKs | Cyclinedependent kinases with various substrates promote + Soindieapparanis cal-cylo progression saassambio - + Gell vides in tw aPC | Anaphase-promoting complox Wiggers Ghromalid separation: ‘oytounesis} egraces Mrohase cyelins. SPF | S-phase promoting factor includes COI and oye, which Disease Association [Prepare cell for DNA replication Retinoblastoma mee | iphasoimaturation-promoting factor incudes CDK and teins, which proms assembly oF tone spine and macear ito the RBI tomar suppressor gene on envelope brosksowm, enromosare 13) 853 —_| p89 is a tumor suppressor tat locks cel eye if DNA is Most common chlshood eye twat damaged + Leukocoia (vite rfl in pup + Srabismas RB__| Retinoblastoma susooptiblity protein a subsvae of COKs | | Spavey® Fei ome BuSoep + “Two-tit mode!’ f carchogenests: promote 41) inherited mutation of one aloe p21 | p21 sa CDK inhibitor that also blocks cellcycie progression. | 2) somatic mulation of second alle arcan Medical 8In order io act on & cal extemal melecules, such as hormones and neurovanemittars, must interact wih @ receptor, In general, small hydrophobic melecules {0.9 coisa, sex hormones, thyreid Mormons, and retincids) can roadly pentrata the plasma ‘mombrane to bind intracellular receptors, which often act a transexiplion lactors to affect gene expression, Wost other molecules bind to oell surface receptors, which include jon-channel-finked receptors (e.g, transmiter-gated chan), G-prataln-tinked receptors (the largest family), and enzyme-linked receptors (¢.9,, tyrosine Kinase recepicrs), These cell surface receptors (ie, the “frst messanger) usvaly transmit their signal via a number of dawnstroam second messengers, leading to a signal transduction cascade. One exception isthe gaseous nitric oxide (NO), which readily dtuses across the plasma membrane t2 activate soluble guanylate ayolase, goniralo cGMP, and promote smeoih muscie relaxation. ‘G-Protein-Coupled Receplor Systems. ne on econ he ais ey ae EES, “esronsye, Tear ote % \ ‘Tyrosine Kinase Receptor 7 ERNE 1 eae i 5) °) ite Envvetne eos Defation of abbreviations: Soo next page. (Continued) medicalExamples of Receptors Produced ram Ahn by Dre: it fines Sranaselr ~ te vascusrEndonelalGote fossa Recaps or ‘ial Lf Vorb Face: ANF) hrc once fo) ite Neobrans coyetsan Pree Kass 6 or Vascular Smooth Muscle 4 t Falsaionf noon Maco Semataton Pharmacology Nitrates Siidenatt (nioglycenn,ritreprussie, ‘sasorbice dinitrate) + Converted to NO, feading io cGMP buildup, causing smooth muscle relaxation arc dilation of arteries and + For angina and pulmonary edema + Adverse ettects: headache, Iypotanson + lahibits phesphodiasterase, leading a cGMP bulup, causing smooth rustle relaxation and dilation of blood vessels, leading fo corpus + For erectile dysfunction * Adverse offects: headache, hypotension Adcenergic Receptors + a, (G,}-emaoth musele cantaction + a, (G,,)-inhibts NT release + By (GT heart rato and contractity + fh (G,}-smooth muscle relaxation Muscarinio Acetylcholine Receptors . ffects CNS, PNS, gasiic MG peta coe + Mi, (G,,)--} hear rate and contractity + Mi, (G,}-stimulates glandular secretions + Mz (Gj) CNS only: rote unctear + Mg (6,)-fo¥0 uncloar Dopamine Recentors + 8, (G,}-smooth muscle relaxation; natriuresis; CNS effects, + 0, (G;,)inhibits sympathetic, ‘ransmiter release: CNS tects + Dy (j.) similar to Dp + Dg (Gig)—sinilar fo D, + D5(G,}-simar to, Vasopressin Receptors + ¥,(G.}-smaath muscle contraction + Vz (G,}-T H,0 reabsorption in kidney ther Receptors Insutn (T}—T alyeogen synthesis; +L lyeogenelysis + Glucagon (G,)T glycogenclysis: { glycogen syns + IGF (TK) proiteration of various cal types + PDGF (TK) proliferation of connective issue, sila and smooth muscle calle + EGF (1101 proliferation of ‘mesenchymal, glial, and epithelial eels + ANF (GC}-ameath muscle relaxation; T Ma and HO excretion in kidney + NO (Go}—sma0th muscle relaxation Doon oF abbreviations: ANE, atl naturte ft, ATP, adenosine wphoxphats; cGMP, oo guanosine monophoaphat, DAG, dlacyllycoro; EGF. epidermal grows fator =, endopasme eevlem: GC, guanylate cycieso-cOuplod recepor G,. CAMP nhiing GPCR; G., PLC-scivaing GPCR: G,, eAMP-activeting GPCR: IGF, sul ike growth factor, PDE, shesshodissiorane: POF. platlet- activation Magoman factor —> plasmin activation Flbrinopeprdos Endothelial damage —> activation Hagornan factor —» thrombin — fibrin clot degradation Leukotriene B, ‘Membrane phosphotipiss of macrophages, monocytes, neulpils, mast calls + arachidonic ackl cascade — lipoxygenase pathway Formyl methionyl peptides Roleasod from microorganismsMonoamine Effects Triggers for Release Histamine Bavophils, latee's, and | Vasocilation and + IgE motistad mast cel reactions mast eas inoreased vascular | + Physical injury permeabiy + Anaphyistoxins (69a are C53) + Cytokines (iL-ty ‘Serotonin Platelets Plast aggregation Enzyme ‘arachidonte Acid Effects Comments Product Cyclooxygenase | Thromboxane Ay Vasoconstriction, Produced by platelets platelet aggregation Prostacyelin (PGI,) Vasoconstriction, Produced by vaacular endothelium Inhibition of platelet aggregation PGE, Pein _ PGE,, PGD,, POF, Vasodilatation = Lipoxygenase 7B, Neutropal chemotaxis | — L7G, LT,, LTE, Vasoconstriction, Siow-rescting substance of anapnyens bronchecanstiton Kinin System + Bradykinin— vasoactive peptide procuced from kininogan by family of enzymes called kalikreins; degraded by ciffrent bepiidases, including angictensin-converting enzyme (ACE) + Activated Hageman factor (factor Xil) converts prekalikrein~> kelikrcin Kallfrein clanves high molecular welant kisinogen (HAMWK) —> bradykinin (produces increased vascular pormeabily, pan, ‘vasodilation, prenchoconstitlon) There are several steps to phagacylosis: enguliment, fusion of the phagosome and ysasome, and digestion, There are three mechanisiné of irtraceluiar kiling, as shown in tho figure: NADPH oxidase-cependent, myeloperoxidase-dependert, ard Iysesome-tapander, Opsanization is the anhancement of phagocytosis wilh IgG andor Cb, Oxygen-independent Killing Oxygen-Depentint KillingChronic granulomatous Deficiency of NADPH oxidase (any one | Recurent infections with catalase-positive Sisease (CGD) ‘of four component pretsins) failure to | Bacteria ard fungt ‘generate superoxide anion, other O, radicals ‘Chediak-Higashi syndrome Granule structural defect Recurrent infection with bacteria: chemotactic and degranviation detects; absent NK aciviy, partial albinism LLoukooyie echesion cefiiancy | Absonee of CD1¢—common fi chain of | RecuTent and chronic infections, failure to form the leukacyta integrins pus, does not rajoct umbilical cord stump The complement system is a set of interacting serum proteins that enhance inflaramation (Ca, C4a, Ca) and opsonization (€3b) and cause lysis of paridles (e.g. gram-negative bactera) via CBi9, The alternative painway is iniiated by surfaces of pathogens. The classical pathway Is activated by AgiAb complexes, ® © © _ inet Sten patehins Aternave Sey Silty — costae ena en ee Ny a cone (Cowes A 6 . Cres Ssoo,g.0.7.8.9-ri % onan Sn oe coreien i SEG Deficiencies in Complement Components. Deficiency Signs/Diagnosis Classical pathway Cig, Ctr, Cts, 02, 04 Marked! increase in immune complex diseases, increased infections with pyogenic bacteria Alternative pathway Facies 8, properdin Increased neisseril infections Bott pathavays cs ‘Racurcent bacterial infections, immune complex cisease 5, €6, C7, or C8 Recurrent meningococeal and gonococeal infections: Deficiencies in camplemant CHNH {hereditary ‘Qvetuse of Ct, C2, C8 regulatory proteins angioedema) Edoma at mucosal surfaces aru, 96 medicalloc Teese important Cell Types Following a bout of ‘ute inflammation Porsistont infections Infctions with carta organisms firuses, mycobacteria, para- sites, unai} ‘Autoimmune diseases Response to forelgn materia Macrophages Derived from blood monocytes. During inlammation, macrophages are mainly recruited from tho bleed (ereusdng manceyies). Macrophages contain aca hydraases, elastase, and eallagenace, secrata monokines Chemotactic factors: 05a, MCP, MIP-t-u, PDGF. TGF Tissue-based macrophag * Connective tissue (histioyte) + Lung ¢pulmonary alveclarmecrophoges) + Liver {Kupter cls) + Bone (osteoctasis + Brain (microg + Kicney (mesangial cots) Lymphocytes (0.9. B calle, plasma calls) + Toalls + Lymphocyte chemokine: lymphotexin Eosinophils Play an important ole in paraaitie infections and IgE-mediated allergic reactions * Eosinoptiic chemokine: eotaxin + Granules contain major basic protein, which is toxic to parasites Basophits: + Tissue-basod basophils are called rast cols, prosant in high numbors in the lung and skin + Play an important rola in InF-mediatad reactions (aFeraies and anaphylaxis), rslease histamine | Higiical 97Feature Primary Response Secondary Response Tine tg armenian | 670 dys Faeays Peak response Smal Lage Antibody ome igi ten a6 Increasing 46, IGA, oF WE niboay ainy viata tw igh efinty maturation) Inducing at Ainmurogens Protein antigens Immunization protoco! High cose af antigen (often with adjuvant) Low dose of antigan {often without adjuvant) ‘Adjuvants incroasa immunogenicity conspecicaly. Thay are given with weak immunegens lo enhance the response. Type of Immunity Acquired Through Examples Natural Fessve moans Placenial IgG transport, colstrum Natural ‘Acie means Recovery om infection eit Passive means Imeunogiobiin or Immune eas given Aaa ‘Aativa means Veecinaton walecular Defect ‘Symptoms/Signs Braton X-linked ‘hypogammaglobulinemia Deficiency ofa tyrosine kinase blocks B-cell maturation Low immuneglcbuln ofall asses. no elreulating B of pre-B colls in bone marrow in normal numbers, narra balk meciates immunity ‘Selective IgA deficiency Doiciency of igA (most Repeated sinopulmonary and gastrointostinal commen). infections. Xsinked hypersght Deficiency of ED40L an High serum titers of IgM without other isotypos ‘syndrome acivatod T coms Normal B- and T-cell pumbers, susceptily 10 ‘extracellular bacteria and opporunists ‘Common variable immunodeficiency Boel maturation defect and hypogammaglobulinemia oth sexes affected, childhood onset, recurent aaciarial infections and increased suscepllity 1 Giaraia Increased risk later in ite to autoimmune disease, lymphoma, or gastric cancer saruay, medical 98SPOILED ea Wie aaa ela Category Disease Defect Clinical Mantfestation Selective T-cell DiGeorge syndrome Falure of fammation of |_| Facial abnormalities, hypoparathyroktim, eiiciency third and fourth pharyngoat | cardiac malformations, depression of pouches, thymic aplasia Tooll nubars and absence of T-cell responses MHC class | deficiency Failure of TAP 1 molacule to transport papties to ‘endopiasmic reticulum (CBF T cells deficient, CD4* T cells ‘noma, recurring viral infections, notmat DTH, normal Ab procuction Combined partial and Tel defidency Wiskolt-Aldrich syndrome Detect in eytoskeletal slyeopretcin, X-linked Defective responses to bacterial Polysaccharides and depressed !oM, dradual loss of humoral and cellular responses, thrombecytopenia and ‘Ataxia tolangiectasia Defect in kinase invcived In the call oyele ‘Ataxia {gail abnormalities), telangiectasia {capillary cistortions in the eye), deficiency of IgA and IgE production ‘Complata functional Be and T-call defclengy Severe combined immunodeficiency (SCID) ‘Defects in corsmon chain af IL-2 receptor (also present in receptors fer WL, 7, 9, -19) Xnked ‘Adenosine deaminase deficiency {results in toxie ‘metabolic products in calls) ‘Dafact In signal raneduetion from T-coll 12 roceptoes Chronic diarrhea: skin, mouth, and throat feslors; epportunistic tungal)infoctons; low levels of circulating lymphocytes: colls unrespenelvo to milogons. Bare lymphocyte syncrome/MHC clase It deficiency ‘T calls prosont and responsive to onspectc mitogens, ne GVHD, deficient in CD4¢ T cells, ypagammagiobulinamia 99Diagnosis Trorsmission |» Sovuc cal: omosenial>haleroumcal n US Catal hones and epi + Parte tana preven erg ase “Hopce eee sanctions — tient noosa sto hoepal wears «ven tant te oa) Pathogenesis: + Human immunodefidency virus (HIV: an enveloped retrovirus containing reverse transcriptase) «Nines cit ett p10 Ms orc) cote tat = Nacrorhages —tompt nae ir donde cts ~Uingenan ote + Entry into cell by fusion requires gp4 and coreceptors — GORS (B-chomokine receptor 5) — SXCR4 (o-chemokine receptor) Diagnosis Y= HV ani 219K tt 1 Met l eontmaton Montoring | G4 cans «SA RA load by PCR Treatment |» Conbiaton arta vtment + Rove angele ehibhore + Protea abo + Prophets ct baa on C04 cot ae Ses co Opportunistic lfetion ‘Common Sites of ntoction Prams owt ani Lang (pour), bone maw ' ycobectorium tubercutosis Lung, disseminated Mycobacterium avium-intraveltulare Lung, gastrointestinal tract, disseminated aces nmi Ling, deomiatd ican capan Ling, sorinatea oyenegnoe Lin, en, arena and garner ack a ro estoina act po sporum pan asonosinal ac ep impo vi Exophaga and nS (ene JC virus Can aire | Seer ant ea ‘sews NS a san : Toros gordi ons Syptococcus neoformans {ONS (meningiis) - - | NS (progressive lita ovkooncsohalopsthy) au: medicalAssociated with Epstein-Barr virus (EBY) ‘Associated wth human herpes virus 8 (HHV8} ‘Gemmon sites: skin, Gl rac, lymph nades, anc lungs ‘Tend 10 be high-grade B-oal lymphomas Extranedal CNS iymphomas common ‘Cervical cancer HIV wasting syndrome AIDS nephropaly AIDS domeniia complex. AnthIY therapy usualy involves three of mere antiretroviral agents, including antimetaboite inhibitors ef retroviral reverse ‘ransetiplase ard viral protoage. These aggressive drug combinations (highly acive antiretroviral therapy, HAART) are picaly intiated early ater FIV infection and wil sften reduce viral load, presarve CD4 counts, ane limit opportunistic infections. Org ‘combinations, as Drug ‘opposed to monotherapy, also slow the resistance to crugs. Mechanism of Action Side Effects and Commants Mechanisms and NRTIs are gansrally prodrugs that Nucleoside Reverse Transcriptase Inhibiters (NRTIs} are listed below) and can cause lactic ackdomia 9 comveried to active forms via phosphoryation. Preverd conversion of viral RNA into dsDNA. ‘sistance mocianisms similar. Some cross-resistance occurs. Druga diffor in axicily profes (major side effects Zidovudine OV, Intibies reverse | + Used in HAART and in prochylaxis folowing neolesticks or ta prevent formerly AZT) transcriptase maternaVotal ransiniselen + Bone marrow suppression—dose limiting, may require transfusions Didanosine (dl) Pancreatitis {cose limting} Zalattabine (ad0) Peripheral neuropathy Slavucine (447) Peripheral neuropathy Lamivudine (316) ) + Fewer side eflects—ild Gl distress, headache + Algo sof in treating hepatitis B Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs) Do nt require metabolic activation; ne cross-resistance Nevizapine Intibis reverse | Provents matornavfetal transmission transcriptase Dalavirdine ‘Major drug intoractions, possible leratogen Fravironz | Halor drug interactions, possible leratogen Protease Inhibitors Inhibition of agpartate protease (HIV protoaso), a pol gene product, prevents viral assembly Inainavir Inhibits aspartate | Gl distress, hyperulycemia, hyperlipidemia, allored fat elsuibution, naphrottiasts Ritonavir protease {grainiain hydration, indinavin), thrombocytopenia findinavir} Saguinavie Noetinavir ‘Amprenavir Lopinerr Fusion Inhibitor Enuviriae Binds gpé7, preventing tusin of ural ana cellar membranes sara, medical 10)Type Effector Cells | Examples | immediate} Basophil, mast | Hay fever, atopic dermalis, insect venom sensi cell anaphylaxis to drugs, some faod allergies, aiegy to animals and animal products, asthma Wfejetexic) | IgG. tM | Yes PMN, ‘Autoimmune or drug-induced hemolitle anemia, macrophages, | vansfusion reactions, HDNB, ryporacute gral rejection, NK celis Goodpasture disease, rheumatic fever I (roncytetexio} | IgG No None Myasthania gravis, Gravos disease, type 2 clabetes rmeitus (immune Wg@, 1g | Yos PMN, SLE, RA, polyartertis nodosa, poststreptococcat complex) macrophages | glomerulorepints, Arthus reaction, serum sickness Wideayed, | None No eT, TH, Tuberculin tost,tuborculosts, leprosy, Hashimoto DTH) macrophages | thyrovtitis, polson ivy (contact dermatitis), acule graft rejection, BVHD, IDDM Cefniion of abbrevietons: GVHD, gealtversus‘host disease; HONE, hemolyie disease of the nowbom; IDDM, Insull- dependent dlabates relly RA, reumatcis erthrts; SLE, systemic pus erythematosus, Clinical Features + Serosite Autoantibodies ‘Systemic lupus erythematosus: chronic systomic autoimmune disease charecterized by 2 loss of seltclarance an production of ‘uteantinodes odes — poe - + Hemelyie anemia, tembocytopenia, | + Females >> Males (MF = 1:9), peak age Antinuclear antibody leukopenia 120-45 years, Atican American > Caucasian IANA) (9504 + this + Mechanism of injury: type Il and I + Sain ast (including classic "walar” | hypersensitivity reactions AnthdsONA (40-60%) rash) + Treaiment: steroids and thor ‘Anti-Sm (20-30%) + Renal cisease immaunosuppressants + Libman-Sacks endocarditis + Neurologic symptoms Inability 10 produce saliva or tears Antibanucleoprotein antibodies: ‘Sjdgren syndrome: an autcimmune disease charactonized by destruction ofthe lacrimal and salivary glands, esciting in te + Koratocanjuctvis sicea (¢ry eves) | + Females > males; age range: 20-50 years and corneal ulcers * Often associated witn rheumatoid arthritis ant aut 102 medical hee, «Se um Soe na eure a Ar SSA 0) | Kee yuan | « a amumne desaes (SLE) ‘CorinaAutoantibodies internal Scleroderma (progressive systemic sclero rgeas; females > males; age range: 20-55 years; acivalion of foroblasts ay growth factorsicyickines leads to fbrosis Clinica! Features Comments ‘characterized by foroblast stimulation and deposition af collagen in the shin and ‘Anti-ONA topoisomerase | Widespread skin involvement Raynaud phenomenan is saan in almost al antinodies (Sc1-70) (70%) Early involvement of the visceral organs | patients and often preceeds other symptoms. + Exophagus—dysphagia + Glitract—malabeorstion ‘Treatment: vascallators. ACE inhibitors, + Pulmonary fbrosis—dyspnoaon | NSAIDs, steroids, ¢-peniailariing ‘exertion Diffuse Scleroderma + Cardiac Mbros's—arrhythaias + Kianey fbrosis—rera} insufciency Limited selorodorma (0.9., CREST syndrome) ‘Anticentromere antibodies | * Skin invelwoment ofthe face and {Calcinosis, Raynaue phenomenon, Esophageal hands ‘dysmaility, Scloradaciyly, Telang|ectesia) + Late invetvernent of visceral organs (telatively benign clinical course) ANSPLANTATION IMMUNOLOGY iS a Grafts Definition ‘Autolagous (autografts) Teeve Is moved from one woaton to ancther isthe sare naval sSyngenele “Transplants babiean geneicaly dential indivi (monozygotic twins) Allogeneic Transplants between ganesealy ferent members ofthe same species Xenogensie Transplants between members of diferent spactes ‘Type of Rejection | Time Taken Cause yperacite Minutes to hours Prelormed anticonor antibodies and complement Accoiorated Days Rosetvation of sensized Teall ‘Acute Days to weeks Primary activation of T ss Chronie Months to years Cac re under: rid mune competes, ow etuar Graft versus host | Weeks to months Grafted bone marrow T oels attack host ara medical 0sIMMUNOLOGY TECHNIQUES IN DIAGNOSIS wn dt _ Complexminturesatcallsare treated with Muorescent dye f labelee antisodiee and wun through the apparatus, The E| Janeen fluorescence actwvated call sorter (FACS) separates the miteon calls into popuiations based on ther levaloffhiorescence wil a panioular dye. A computor-generated disgram Is created. Each detonthese lagrams represents acel hat has oound to a fuorescont-iabeled antibody. Inoreasing fuorescence Intensity with one dye is represented as fa fise on the yaxis, and incroasing fuorescence with the other dye ccows as you mova right on the xaxs Doubieinbeies cells are always found in the upper right quadeant Celis that have only background torescence with ether dye ere found in the lower left quadran Og ‘The results of low cytometry are often shown for quastion soesueee analysis, Be Sure to know the key CD markore and tha biolagic unetions of the colls thet possess them, STEEP is) se | wT cehos walle saves Gytokine Clinical Uses Aldesteukin (IL-2) 1 amonocyie differentiation and 7 NK—used in renal cell cancer and metastatic Opraivekin (IL-1) T Platelet formation-—used in tirambocytopenia Filgrastin (G-CS*) 1 Granulacytes—used for bone martow recovery Sarat (ONLOSF) T Granuboyos and macrophages sed for bane rtrow ecovery Enyttropoietn “Anwrriae, eepecaly assocaid wi ronal falure Tirombopoiein ‘Tivemboeyiorenia Inoreron- Hesais Band 6 oukorinsmagnant melanoma, Kaposi sarcoma inteteranp Muito serie interterony Crone granulomatous disease Ft TNF | ie medicalAzathioprine Converted mercaptopurine, whose metabolites inno purine meiabatsm Cytatoe w proterating hymahonites (especialy Tells) Auicimmune diseases (@.g., SLE, rheumatoid ‘artrits) and immunosuppression in renal homogratte Cortcasteroids | ayniheais af prostaglandins, loukotionas, ‘Cancer, organ raneplants ‘evtaknes; Inhalt T-eall proliferation; at immunosuppressive doses, Hey aro cytotoxic to some T cals Cyclophesphamide | Cyoloxe to prolerating lymphocytes (especially | + Autoimmune diseases, bone marrow B calle} ‘rensplanis + Similar cytotoxie drugs: aytarsbine, actinomycin, mathorrexata, vinrstine Cyeiesporine ‘Antiiotc that binds to eyciophilin ~ inibis + DOG in organ or tissue traneplantation calcineurin cytoplasmic phosphatase) > 1 (mycophenolate + steraids + cylolexic ‘activation of Tcell transcription factors — drugs) 1L-, IL-3, and interferoney + Side eilects: peripheral neuropathy, nephrotoxicity, hyperglycemia, hypertension, hyporipidema, Nrsutsm, gingival overgrown, cholelithiasis “Tacrolimus Antbiotis that binds to FK-binding protein + Used altemativay to eyciosporine in onal (FBP); oso inhibits calcineurin {similar to ‘and Wer transpiants cyeiosperine} + Side effects similar fo cyclosporine Mycophenclate ‘nhibits de novo purine synthesis * Kianey, liver, heart transplants + Used with cycosaorne in ronal tansplants 12.1 ayclosporine dose RAD immune globulin ‘RhoGAM™) Antibody io red-cel: RhD antigens ‘Administer fo RhD © mother within 72 h of ih & delivery to prevent hemoiyte disease of newton in subsequenl pregnancy Monoclonal antibodles ‘See dactiximab,infiximab, muroamanat in table below MAB Clinical Uses. Abehimals Aaliplatelet (acute coronary symptoms, post angioplasty) antagonist of Illa receptors Daaiximab | Klcney tansplante—blecks IL-2 receptors Invi Rheumatoid arthiis and Crohn diseasa—binds TNF Muromonad | Allograft rojoction block in renal transpants-—binds the T3 (CD3} antigen an thymoayes Patvizumas | Respiratory syncytial vitus—blocks RSV protein Ritwximab 'Non-HodgdinIympnoma—binds to CD20 antigen on B-cell surface protein ‘Trasiuzumab | Breast cancer—anlagonist lo HERZInou receptor ‘ariay, medical 05Microbiology ‘General Principles npn of Medically Imprian AizobilGOUES aso Vea Genes. 18 Bacteriology Atte Ages es ceceseneesees HAEO Bacerial Growth Curve 108 Fungi Fests Bacena.. seeaceeeseassensssesn 9 Rang Oven pecan eB) Noval Raa Ogi, no ———_Nonssteri Funga ectons eee 8 Baca os seosceenesereneense TY SytmicEung fects even elb jot ins mn Ccpportrsi ung 183 etn aogier nd igo eS. 12 nga gets a Uns Croorh equiemens seen me, Bera Cont, ns atibacterial Agents ecanis Ation of Ai ABET oe (Ca Wal Sythe ibis. Summary of techni of Protin yess Iii. Protein Sythe nba, Folie Ae Sess rhibters on cee iA Relation ition pessseseiee sect MBcelaneaus. ne Parasites (bigate aelar Frets 1" Feats nae Pacis. . Ww Pieters “0 Protazen Paes. eevee lB Feet bse Ta Occ mec Mia, 21 Pismadlom te cide cesteieessesaeneseeeeeT Pasmodium Species. 10 tine Bags 120 averse eso tier Dg... we 0 Hemodlaglates mm Aeerenus pcm etn od rests. m2 jor rotocal netiors and rugs ol Chie m etamans: Worms Temata ute} Diseases... sessevtir nnnersee TS Cetin Cade (ager) ms FRovndworms (erated. sserssseeeee Roundtorms Nematodes) Tensrites by Eggs ns oungworms(Memaades} reared by Len. coe Virology DNA Vises, Dubie sronded RNA Vrusts: Reva. sce PostivesSence RNA Vises. Nagas Sone RNA VisesGENERAL PRINCIPLES OF MICROBIOLOGY Characteristic Bactoria Fungi Parasites Diamotar Minute (0.02-0.8 w) ‘Smal (03-2 w) 10 15-25) {ophzotes) ‘Goll ype ‘Acollular—ro nucleus Prokaryotic cells Eukaryot calls = DNA or RNA + DNA ane RNA = DNA and RNA, 1 rudeceapsld, except in| +1 chromesome + More than one chromosome segmented or cipiid vinuses_| + No histones Replicates in Rest cols DONA replcatos G and S phases continuously Evons, ne introns Irtrons and exons Some have polyistionia Mono- and polyeistronie | Monocistronic RNA mRNA and pestransitional | mRNA cleavage Uses host organelles; obligate | No membrane-bound | etachancra and other memrene- inaceluor paresites organelles ound organelles No ribosomes 708 rnosomes {805 ribosomes (40S+60S} (s05+508) Cellular mombrane | Some are enveloped, but to | Membranes nave Membrane Sterels, such as rmemevere tuncion ne storols, excopt ‘ergosterol is | cholesterot, Mycoplasma, which have | rajor sterol cholesterol Cell wall No cell wall Peptidogiyean complex No cell wall catbohydraie call wal: chitin, ‘lucans, or Replication Make and assemble val Binary fission Gytokinesie win | Gytoknosia with components (asexual ritesisimeesis | miosismeosis Loghumr otc TaPLAN, toa ~medical ez Neatai lie Releng + Dotoxiying modturn Turning en anzymos to utize medium Log Pras + Rapid exponential growth + Genoralion Uo —tine it 2kos one ello cv info two + This dotormind during log ahase Stationary Phase: + Nuients used uo + Toric products begin to accumuiste + Number of new cols = the numberof dying celts Death Phase: + Nuttents gone + Toxic products kil cats + Number of cals ying exceeds the number of eats dvsEnvelope Structure | Gram @ oS Chemical Composition Function Capsule (oonessentat) | Both Gram ® anc Gram , Polysaccharide gel except + Antipnagocytic + Polysaccharide B. anthracis) + Immunogenic (except S. pyogones and N. meningitis, type B} Gram ony Phospholisidroteins Hycroprobic membrane: LPs: + LPS = endotoxin + Lipid A + Lipid A= toxic moiety + PS =immurnganie portion Inner and outer membranes: auernentone pose | Aimer ded { Protsin porins Passive transport eit rrr Pesicaen pans | Reser ta at pone | Grn ee: Se ae eae Cheactiateranne | = Sneed oy penis Maen «pols aneratone | ie onto «Baste emowauppaer” | maneets a + Sleaton pow senaeve * Semana near Tengen | 508 | Gram@and Game | Pasnigmeaies | > Glviaton * Fancon Perec rue Siornamsare |S Yoohana Src 5 serene «Rete feacssumdava |" qemu oo 5 aya « Ctarse | apotere | ge aay tory vs ‘irvegularities: * Oral absarption «Sb pnoa epee toa + Brucelts ae ‘multivalent cations: en + Photosenatviy + Vester teeny viaaoides | 08 ~—~*| «Gram sone” Myton ct |» liaton Ustln aia Syn, Gane Meawgsto sn eos: | * Snccuce eure : saree « Ciamyeta Invest itt |. ome + darithromycin: + Mycoplesrms: multidrug exporters + Skin rashes: * Urspoome ee * togoneia + Campsite Ghodemer | 808 | Narow peczum | wonton ot | > Glirtmten = Gan trorwectes | Braegese ont |. Sunean * amate Supeifetion ninogyeaes: | 305 ——| Gas Se Posemeaaied | Cron Neon fr bowel perme Ciropmreces | cesety tren ay bone + eon finer ‘mazotinonos: | 605 | Gram@eecc! | Resblance are | » Tivonbooytaporia’ |) Wo cosoeltnoe tezoid nourapenaeap.h_| wih omer pre Irmunecomororised | Sytvocts Bes + MAO innaiien | aoston esoved (dietary and drug for rogistant rete) tnocsone medical 15mune epee anamRt ovate te unin obs vi tate “Tia NY — grhenalrn re Tend Mechanism of Mochaniam of ‘ClassiDrug, ‘Action ‘Spoctrum Resistance Toxicity Notes: Sullonanides | PABA Gan, gan | Decreases ~ Fypesersiviy | Combed win animeabotio | Shay” | secanuton ct | eeentecania | emetor or Tue tacteial | Nosaate’™” | Gage devoases |” OSRMGSEAS | tence etosy diyareteroato Siyoravorr |, Roerbde reer Seoeteae | _ Nemmoncty Siig lle tyro * eras a: synthesis neweoms Timewepim | ibis becamst | H honzee | Procalon ~ wegaonasio |» Adverse fet nyotoate | be eatrois | efter mee rayon road fetus, hus diysrefote |. tecgooenta byeonarent rombing le reductase sin | | Geto | ttn ace Snes teerenned tity eee for orug because Itls Berto ning tehonged ae ow ie Mechanism of | Mechanism of Class/drug Action ‘Spectrum Resistance Toxicity, Notes Fiuoroqunoiores:| herewith | Gram@rovs, | + Doaeaved iacshiar |» Glstess | Contandosied Pemetomar | boca Dus | CNowsera’™ |” crgeoeentalons | suinsh” | inoregnoncy omer Popocemere | cea) nou oc an aan ercanige : IPanawions | Gens | sneaker pe ‘Soreion, levorloxacin ‘oyrasei, resulting + Alteration of drug's ‘abnormalities in Pentti ot orang re rel ses Braet Class/Drug Notes Metronisazole | When reduced, | Anaarobes Fara plasma. | + Glelatoas + Steeng metalic taste ‘nlerieres wiih | (exept mediates + Disutiram-ike | » BOC in fueete acia Actinomyces) | resistance reaction with pseudemembranous gynthasis alcohol coils (bsctercidaly + Pesipheral neuropathy, axa Definition of abrevistione: DOC, arug of choice; GEPD, glueose-6 phosshste dehydrogenase; PABA, pars-aminobenzcic ac UTI, unary ‘tact infection Wau medicalPARASITES + Cannot be cultured on inert media, intracefular organisms (both obligate and facultative) protected from antibody and complomant Intracellular pathogens tend to elicit cell_nadiated Immune responses, so and pathologic lesion frequently a ‘granuioma + All rickettsiae, chtamydiae, Mycaboetertum leprae + All virusos + Plasmodium, Toxoptasma gondi, Babesta, Leishmania, Typanasome crust {amastigotes in cardiac muscle) + ive inside phagocytic cells in the body, but can be cultured on inert media + Froncisata tularensis, Listeria monocytogenes, Mycobacterium tuberculosis, Brucela species, nontuberoulous ‘mycobacteria, Salmonella typhi, Legionella pneumophila, Yrsinis pests, Nocardia, Borrelia burgdorfen, Histoplasma capsulatum Flagollates Important genera_| Entemoeba Lume, (Gur, UB} BiooolTissue Neegleria Trichomonas Plasmodium Acanthamoeba Giardia Toxoplasma Hevor.asecuares Babosia Leishmania Innes TINAL Trypanosoma Cryptosporidium fsospora Ww| Disease/Organs Most Entamoeba + Amobiasis: dysentery | + Cysts Mstronidazole histolytica + Inverted, flask-shaped | « Fecaloral followed by + Liver abscesses: "spokes" ‘9 fining of duodenel beaver, muskrat, “string” test) fatty, foul-smelling transmission: water, oe diarrhea (diarrhea: food. day care, aral- i te = eee Se ee - “ © & 118es Goeces [Cheetos Franson | Open tunes [Pomayamtc_| Par signer |» Mes tephc | pps Tarivcniinate |"aataruie | aetusernnss | otoscomaa Ropeacttiey | RAS aia |” Stoners feulreee | iyamrnti,| ences, mercer Seti te Feobanons Kea cain | Fasingmie | Groene __| Fas ge patients; insicious onset contact lens solution | + Culture as above propemisine Eipopecannac | Giro ioe ec ee Tear Each Plasmodium has two cisinct hosts: ye, liberating a new crop of merozoites. Dafiniion af abbrevietons: CSR, exrehroxpinal Told; GAE, granulomatous amraabie encephalitis, + Avertebraie, such as the human, where asexval phase (schizogony) aes place inthe liver and rad blood cells + An arthroped hest «Anopheles mosquito), whore gametogory (sexual phase) and sperageny take place Disease Is caused by a varity of mechanism, including metabolis. of hemcglatin and lysis of infacted calls, leading te anemia ‘na to agglutination ofthe infectes RBs, Paroxysms (chils, fever spe, and malarial rgore) occur weron the infected RECS aro ot me sen exyieayre Doliiion SF abbrovalon: RBCS, ed Bod Ba, medical 19Species Disease | Important Features | Blood Smears Liver Stages. Treatment Plasmodium | Banign | 48-hour tever spikes | Enlarged host Persistent ‘Chioroquine PO, vivax terian cells; ameboid trypnozoites then primaquine lwophazoitos Relapse" Plasmodium | Benisn | 48-hour fever spikes | Oval jagged, Persistent Chloroquine PO, ovale ‘eman Infected Race hyprezettes then primaauine Relapse Plasmodium | Quarlan or | 72-hour fever spikes; | Bar and band forms; | No persistent Chloroquine PO, ‘atariae malarial | recrudosconco” rosette schizenss "| stage" (0 radical core necessary) Plasmodium | Malignant | hregular fever spices; | Multiple ring forma | No parsistent Chloroquine fateiparum | rertan | caures carabral malaria | erescantshaped | stage” resistance a gametes problemt Dofnaion of abbreviations: PO, by mouir: FE, ree bisod cas. *Roorudccoanoe Isa rourrence af eymploms from kaw vals of erganisms remelning in red cols, Relapoo Is an exaoaruation Irom Jvor ‘stages (hyprozoites} Use quinine sulla plus pyrimetharine-sulfadoxine, 1. Suppressive {io avoid infection) 2, Therapouti (eliminate erythrocytic) 3. Radien! cure (eliminate excerythrocytic) 4. Gametecidal (destruction of gametocytes) ‘Successful treatment is accomplished with chleroguine therapeutic, and gamelocidal, whereas primaguine eliminates the axoerythrocytis form, llowea by primaquine. Chloroquine therapy is suppressive, Chloroquine-Sensitive Malaria P faetoarum Chloroquine P malin Chiorequine Pan Chloroquine pus prmaquine Pevale Chiorequine plus pimaxine ‘Chloroquine-Resistant Mataria Prophylaxis: mefioysine; Backup drugs: doxycycline, alovaquone-proguani Treatment: _quinino 4 elfhor doxyoyatine, clindamycin, or pyrimethamine AES GENGee ee Drug Side Effects Contraindications and Cautions. Chloroquin Gl cisivess, pruritus, Headache, dizzinass, homolysis, | Avoid in psoriasis hhydroxychloroquine | coular dysfunction Meloguine VO, dizziness, syncope, extrasystoles, CNS effects | Avoid in seizures, psychiatric disorders, (rare) and in cardiac canduetion defects Primequine Gl cistress, headache, dizziness, neutropenia, hemolysis | Avoid in prognancy, G6PO deficiency. and autoimmune disorders Quinine distress, cinchonism, CNS effects, hemolysis, ‘Avoid in pregnancy hematetaety _Dofinion of abbreviations’ CNS, central nervous system, vomiting, diacthea, no iédical |, gastreintestral; GEPD, glucase-6.phosphate dehydrogenase; NUD, nausea,‘Hemoflageliates ¢trypanesomes and |eishmaniae) infact blead and tissues. They are found in: "Stir toes Se tneemasigans wt ages sn an nate memerane | Tau on amaatiote (ove cule having reir the gelum or undusting amban Vector/Form/ species | oasase Tranemisson | Reserve Diagnosis __| Trostmont Trypanosoma |» cragar dase | Reduvid ug [= Cate dogs | Bootie, | Wrox rer menses" | Tettmearsone |” Sacer’ | eyporestgetes Sree) | Sgr pcs erect + Latin America Triatome) passes + Poverty housing 1 eiamotea | Gypomaaigae Smairg cond | tae a) ge Goma | Tee tus amine eSninron se Sen ime Tysanaroma | vatican soopng | Taporasigaen | tamara come |= Tapomesgot | » Ace wee scene iamee | imersrucek, | tadannes™ |” irecaangee” | Seon silane | tmmmorme | sateontee tae oe “ane Trypanosoma b | + Antigone aed Cpt Maisie |* Saas Frmaregitvin rosea Terman |» Vise Sendty the | Utrstomane | amastigotes | Stolen Seenle | i ioarnamere | Anette | Suture een caianmanie | Guan Gandhi tno] vhs tarane | amantigatos n | Stooge ceienmacte | Coo 1 Beersnamere | Aneydoerin | Soa different species) | {Oriental sore, etc.) and wikd arimals | culaneous lesions terepmania | wuczononame | Sonanyere | urannumane | Same Soscnate weeenas | teatro 1 Rin ton a complex ‘and wild animals ‘Defintion of ebreviatins: CDC, Center for Disease Prevention and Gantrol, OS®, cerebrospinal Told *T.onuak An estimated 0.5 rion Americans are infecte, creating some risk of transfusion transmission in the United States. In babies, acute Wfections are ofen seriaus and valve the CNS. In elder cnildren ane acu, rill acute latections may aeacme crane with the isk of development of eardiomyopatty and hear aie. ‘Al Leishman: invacelulr, sanctiy vector, stboglzconate mwSpecies DisoasclLocale of Origin Diagnosis | Troatment Babesiaipimariy | Bebesicss (hemi, malarastike) Geensa sin | Candamyen ls disease of ie} | Samo range as lyme: NE. N. Cert ottin smear | quinine Humane: Baboat | Csitoia, aed NW! Uses States erhanster ‘mera, WAT nd Inoculation Hot stains Toxoplasma gon |» Rost common parasitic cseasa Catis essential | Serabgy: Prrimethamine + infec after bith aro most commonly | definitive host, | igh igy oc | nus suadazne asymptomatic or i: way rime ‘many ator tong gM aoute tmoncnuclocsis animals are nese + Produces severe disease in AIDS or otner_| "Ciel hosts Inmunccampromined + Primary matsmal infection during Mode: brognancy may infect fetus: + Raw moat in = Severe congenital nections US. bork is Ht {innacereoralcesfeaons, + Contact with cat hororetnts nyére ormeroceptay, |” toca ‘suzutes) H Toxoplasma eroseos tho placenta early = Later term congenital infection may prosioe progressive blindness ‘MasOR PROTOZGAE INFECTIONS AND. DRUGS OF CHOICE Infection Drug of Choies Comments “Amebiasis Metronidazole Diloxanid for noninvasive inlostnal amebiasis Gases Metronidazole o furazolidone ‘Becknacers dares" fom contarmnated wae of “Tehomonionia Metronidazole ‘Treat both partners Peumacystosis | TMP-SMX ‘Alovaquave or pentamidine IV are backups ‘Toxoplasmasis Pyrimeshamine ard sufactazine ‘TMP-SMX ie aso prophylactic against Preumagystis arin isAIDS Letshmenios's Stioogtuconste = Trypenosomiacts | + Niturimox (Chagas dieease) — + Arsonicals, pentamidine, suramin (Xtcan stooping siemnoss) are kee eee Phylum Flat worms (Platyholminthes) Roundworms (Nemathelminthes) Class (common name) | Trematodes (Tukes) Costodos (tapeworms) Nematodes" (roundworms) oi Fesciaie Diphytobetbrium ‘Necetor Fasettopsts Hymenotepis Enterobius Paragonimus Taonia ‘uchereriavBrigia Opistorenis Echinococcus Ascaris and Ancylostoma (Glonaranis) “exocara, Tehuris, an Tichines Schistosoma Drchocerea Dracuncuts Eyeworm (Loa ia) Stongyoldes ‘olazoans also Weise te AnRrepada, waich serve mainly 69 lsrmediae Roste ihe eustasenna) or a8 vedlare of daaase (he Arachrida and Insecta). ‘Nematades mremoric tum the "W" upsidedown) eau 2 medical“Tramatodes: * Are commonly called flukes, which are generally fal and fleshy, leal-shaped worms + Are hermaphrodite, except for Schistosorna, which has separata males and females + Have complicated life cycles ecouring in hwo or more hosts + Have opercuintes eggs (except for Schistosoma}, which contaminate water, perpetuating the life cycle, and which ara ako used to diagnose infections +The first intormediate hosts are snails Reservoir Progression in| Important Organism Common Name | Host ‘Acquisition | Humans Ova Treatment ‘Schistosoma | Intestinal Cats, dogs, | Contact with | Skin penetration — | — Praziquantel ‘manson schistosomiasis | catte, ete. | water; skin | (itching) > mature in S. faponioum penetation | veine of mosontory eggs cause granulomas in tver {liver fbvosis in ‘chronic eaaea) Schistosoms | Vesicular Primates | Contact with | Skin pensiratien — | — Praziquantel ‘haematobium | schistosomiasis water: skin | (itching) -» mature Penetration | in blacder veins; chronie infection has high association wth ladder carcinoma In Egypt and Africa Nonhuman Swimmersiteh | Bics Contact wth | Penotate skin, = “Trimeprazine, ‘Schistosomes (Great wwatar; akin | producing calamine, Lakes, penetration | dermatitis without sedatives US» further develoament In oumans; ening is most intense at 2 10 3 cays Glonorehis, Chinesoliver — | Docs, cats, | Rawtish | — Operculated | Praziquantal sinensis fluke fumans "| ingestion e098 Fasciola ‘Sheep liver fluke | Sheep, | Ingestion | — Opercilated | Praziquantel hepatica cattle, of aquatic eggs humans | plants watererass Fasciolopsis | Giant intestinal | Figs, dogs, | ingestion — | — Operculates | Praziquante! buski uke rabbits, | | ofaquatic eggs ‘pumans | plants: water chesnuts Paragonimus | Lung fluke Humans, | Raw crabs, | — ‘Operated | Praziquantal westermant cat family, | crayfish eae igs ‘aru, medical 2:* Consist of tee basic portions: the head or scolex; @ “neck” secon, which produces the progiattis: and the segments or Progiotiss, which mature as they rove away fom the soolax + Are ciagnosed by finding eggs or proglatils in the feces + Have complex life cycles Invoving extraintestinal larval forms in intermediate haste; when humans are intermediate host, these Infections are generally more soriaus tan intestine infections with adut tanesworms Human | Diseasa/Organ Cestoge (Common | Ford Host” | Iavalvementymptame Name} Transmission | Type | (Ss) Diagnosis | Treatment Tonia saginata eer | Ingosion crave st | DH | Intestinal tapewormaral! | Proglotids ” | Presquarl tepoworm Corainngeystiorl wiecine wave nfo eae + Sie asympomat or vague Or aan atomin ne Tania solu (pork | Wt vegetation, | M_ | Gyetceromeiiggs ava | Blo Prasat ‘epecomm) ‘oe contamina Savoop intra oo, hear sirgey in one wah ome ting tome shes ara sutinfocton Di: humans evsoping | Rea rork | pyy | Inet tapeworm rogltice oe | Pecqunt and Save saurtoe | conning he “Sesame aefor Tone | gga foes tyatorl ingest Seaiata oynmane Dipnytabotrium | Onnkngrondwarer | IH | Sparganosisianas toner Praca ‘etm ish Sinn copepods penetate sta a tepoworm toustaaery Eroemvat 2 IMs: crustaceans —» | eaying the larval fish; rare, humans | forms or frogisrake DH: humansimannmals; | Poubiees 20! lake rogions ara, raw pickled | DH Infestinal tapeworm (up te | Proglatids or | Praziquante ‘ish containing a 10 metersysmal intestine, | eggs in feces sparganum megaloblastic anomia Echinococcus Ingestion of eges | I Hydatid cyst disease; Imasing, Surgery, ‘granulosus fvor and lung, where cysts | seralogy albendazole TH: herbivores; rar: containing bload capeules urans develop Di: carivoras in shoep-alsing areas Echinococcus Ingestion of aggs | 1H Alveolar hydatid cyst incu as | Surgical ‘multilocularis, disease above, butne | resection 1H: rodents protascolicas Ht canines and oats; Nosthor areas Detnition of abbreviations: H, termediate host DH, dfintive host erin na medicalRounsworms are transmitted by: + Ingestion of aggs (Enteronius, Ascars, or Tchunis) + Dirac: invasion af skin by larval forms (Necatar, Anoylestoms, or Strongyioides) + Ingestion of moat containing larvan (Trchiota} + Infection invoWving insects transmiting the larvae with bites (Wvucherera, Loa oa, Mensonsila, Onchocsrca, and Dracunculis) (Bogeat scars) Until they ais, cause Inftammation ‘om eating it in yard (pica) Disease/Organs Most | Form! Species Affected Transmission Diagnosis | Treatment Enterobius vermicularis | Pinworms, large + Eogsiperson to |» Stay awab of | alnendazcle Intestine, perianal tering | porson poriana aro | Treat ene faily {ost roauontholminth + Autoinfection | + Ova have paras inUS} flattonod sido with larvae insido Tiichuris wichiure Whipworm cecum, | Eggs ingested Barralshaped | Albendazale ppercicis, and rectal eggs with Prolapse bipolar plugs in stools ‘Ascaris lombricoides | Ascariasia Eggs ingested Bile stained, | - Supportive therapy Ingest ecg - larvae knobby eggs | curing pnoumoniis {Most commen helminth | sTigrate through lings Adult35 to | + Surgery for ectopic ‘worldwide; largest {cough) ene mature in 40 em migrations roundworm) ‘arrail inlastine; may + Albendazole obatruct esti ar bilo uct Torocara canis or cat | Visceral tarva migrans | Eggs ingosted'tom | Glnical fangs | Alvondazol: selt-imitng Larvee wander aimlessly | handing puppies or | andseroegy | in most casesSpecies Form/Transmission | Diagnosis ‘Treatment Necator americanus Hookworm infection Fllarform larva Fecal lavas (up to 13 | Mebendazole (New World hookworn) | Lung migratton + penetrates intact | mma) and ova: oval, | ana iron therapy noua kin of bare feet ‘ansparant with ing -> anarnia 28 callstage visible Blocasucking -> anemi 73¢ Fecal aceuit blood ay be present Ancylostoma brazitiense | Cutaneous larva Fiariform larva Usually a presumptive | Thiatendazale Aneylostoma caninum — | Migransiintense skin Penetrates intact skin | diagnosis; exposure (doa and cat heokwanns) | itching but cannot mature In humans ‘Strongyloides stercoralis | Threadworm Flarfonn larva Larvae in sto, ‘Thlabendazote strongyloisiasis penetrates intact | serclogy Early: anaumontis, Skin; autoinfection ‘abdominal pain, diana | leads to indefinite Later: mslabeorption, infections unless Uucers, Bleody sicols | ested Trichinella spiralis ‘Trichinosis; larvee encyst | Viable eneysted | Muscie biopsy. clinical | Steroids for inmuscie > pain larvae in meat are | findings: fovor, severe vonsumed: wildgame | myalgia, splinter symptoms and eat hemorrhages, mebendazole eosinophilia sna : ss B ee Virus Family | DNA Type Polymerase | Envelope | Area of Replication | Major Viruses Parvovirus ‘ssDNA No. Naked Nucleus: B19 Papavaviris dsDNA Ne. Naked Nucleus Papitioma Circular Polyoma ‘Adenovinis| dsDNA No Naked Nucleus Adenovieus Linear Herpesvirus dsDNA No Enveloged | Nuceus, assembied in | HSV, VZV, EBV, CMV Linear Nucloar nucleus Poxwirus dsDNA Yes Enveloged | cytoplasm Varola, vaccinia Linear Molluscum contagiosum Hepadnavius | Partaly ¢s0NA | Ys Envolopad | Nucleus via RNA vv Cireuiar Intermediate Dofiniion of abbreviations: CMV, ofemegalovrus; ds, double-svarded, EBV, Epstein Sarr viusi HBV, hepall B wus, HEN, herpes simplex virus; 85, single-stranded W2V, varicella-zoster virus ne medicalEnvelope Shape Reovirus | + Linear dsRNA Yos Naked + leosahedrat + 10-11 segments + Double shelled Family RNA Structure | Polymerase | Envelope | Shape Replication | Major Viruses Calicvius |» asDRNA, inser | No Naked Ieosahodral | Cylopiasm + Norwalk + Nonsegmented + Cruise ship agent + Hepatitis E Pleomavius | + ss@RNA, linoar | No Naked Teosanedral | Gytoplasm + Pala, ECHO, + Nensegmented Enlere + Rhino, coxsackis + Hepatitis A Fiavivies | + ssRNA, linear | No Envalopad | leosahedrat | Cytapiasm Yellow fever, dengue, + Nonsegmented Togavians |» BsGRNA, linear | No Envelopod | Ieasahodral | Oytoptasm + Nonsegmented WEE, EEE, VEE Coronavirus | + s8GRNA, near | No Envolopod | Helical Cytoplasm Coronaviryses + Nonsegmanted SARS agent Retrovius | + Diploid RNA- Envelopad | leosahedral | Nuoleus HIV + a8 RNA, tear | dependent fr truncated um + Nonsegmentad | ONA conical Sarcoma polymerase Daiiniion of abbreviations: EEE, easier equire encephalitis, HV, hufhan Inmmunodelidency virus; HTLV, Ruman Teh ymphocytoronie vius; YEE, Venezuelan equine encepralis; WEE, western equine encephaits,‘Area Where virus RNA Polymerase | Envelope | Shape | Multipies | Major viruses Paramyxovius | + soGRNA inoar | Yoo ee Vialeat | Cytopiaam | mumps, measias + Nonsegmentes FSV, prainuenza Rhabdovirus + s98IRNA, linear ‘os yes Bullet- Cyopiasm Rabies, VSV + Nensegmented shaped, nokia Flovnee + SERNA, near | Yes Yes Helcal | Gylonasm | Marburg, Ebola + Nonsegmanted Onhamyrovius | = ssGRNA near | You ves Heica | Gytoplasm | Infuonca 2 a eagments and nucleus Bunyevis | + ss2RNA linger to | YoS Yes Hales’ | Cylons | Calfomia and ‘irealor Lacrosse + Scopes, encephat, ambizense Hontavs ‘Arenas + s9GRNA circu | YOR vee Hele | Cytopiasm | Lymphoortc + 2 segments: 1 choriomeningitis sense, }ombisense sins, Lassa fover Detniion of abbreviations: 3s, doublestranad; RV, rospralory syncytial vis 6, single-stranded; VSV, vesicular stomatitis vis, Phenotypic mixing | * Related viruses coinfect coll vis A ard virus B) + Resulting proteins on the surface are @ mixture capsid of AB around nucleic acid of eltor A or B Phenotyplo masking | + Rolated viruses coinfoct coll (vitus A and virus B) + Gapsi¢ of proteins of virus A form around nucleic acd of 8 ‘Complementation + Two related defective viruses infec: the same oal thay aro davective mcifferont genes, val progeny (si with mutated DNA) wil be formed lf they are defective in the same gene, no progeny will be formed Coiniscton of hepatitis 8 and D 's a clinical example of cemplementation where HBV supplies the osded surlace antigen for hepatitis D ‘Genetic reassortment “Two diferent strains of a sagmantad RNA virus Infect the same coll (gonatic shift) + Maier new genetic combinations aze produced through “shutling,” resulting in stable and dramatic shanges ‘Genetic ari + Hinor antigenic changes from mutation + Ocours in many viruses, particularly RNA types + Most noted in HIY and influenza Viral vectors “+ Recombinant vinises are produced that have combinations of human replacement genes with the fective viral nucle acid 8 Medical