Robbins Essential Pathology - Hemodynamic Disorders & Shock (PDF)

CHAPTER 3 Hemodynamic Disorders, Thromboembolism, and Shock 37 perm urer...

CHAPTER 3 Hemodynamic Disorders, Thromboembolism, and Shock 37 perm urer passage, were ey resu n para or compee occu- embo odge n e ower exremes (75%) or bran (10%), bu no son. he major consequence o embozaon n mos vascuar beds s organ s spared. scemc necross (nfarcton) o afeced ssues; one excepon s e he consequences o embozaon depend on e caber o e ung, wc as a dua bood suppy a proecs agans narcon. occuded vesse, e coaera suppy, and e afeced ssue’s vuner- Nevereess, crcuaor y canges assocaed w pumonar y rom- aby o anoxa. Because arera embo oten odge n end areres, boembosm oten cause sgncan cnca dsease. narcon s a common oucome. Pulmonary Thromboembolism Nonthrombotic Emboli Pulmonary emboli originate from DVTs and are frequent causes of In addon o rombus, embo may be composed o oer subsances. morbidity and mortality. hese oer orms o emboc dsease end o occur n dsnc cnca Pumonar y embo cause abou 100,000 deas per year n e sengs: Uned Saes. In more an 95% o cases, e embo orgnae rom    Fa embosm. Sot ssue crus njures or racure o ong bones romb wn deep eg vens proxma o e knee. Fragmened (wc ave abundan a n er marrow) can reease mcroscopc romb rom DVTs usuay pass roug e rg sde o e ear a gobues no e crcuaon, causng a embosm syndrome and become arresed n e pumonar y vascuaure. A more compee n a mnory o paens (Suppemena eFg. 3.2). hs syndrome dscusson o pumonar y embosm s ound n Caper 10. he cn- s aa n 10% o cases and s caracerzed by pumonar y nsu- ca and paoogc eaures assocaed w pumonar y embo var y cency, neuroogc sympoms, anema, rombocyopena, and accordng o e sze and number, as oows: peeca beedng. Bo e mecanca obsrucon o sma ves-    Most pumonary embo (60% to 80%) are sma and cncay sent. ses and oxc efecs o ay acds reeased rom e pd gobues W me, ey undergo organzaon and eer become ncorpo- on nearby endoea ces cause njur y. raed no e vascuar wa or undergo recanazaon, somemes    Amnoc lud embosm. Amnoc lud embosm s a rare bu ser- eavng bend brdgng brous webs (Suppemena eFg. 3.1) ous compcaon o abor and dever y (1 n 40,000 brs) a as    A arge embous may occude e man pumonar y arer y or odge a moray rae o approxmaey 80%. I s responsbe or 10% o a e burcaon o e rg and et pumonar y areres (sadde maerna deas n e Uned Saes, and 85% o sur vvors ave embous), somemes causng vruay nsananeous dea. permanen neuroogc decs. Amnoc lud and s conens    Smaer embo may obsruc smaer, brancng areres (Fg. 3.10). ener e maerna crcuaon roug ears n e pacena mem- he subsequen rupure o capares may cause pumonar y em- branes or e uerne ven (Suppemena eFg. 3.3). he onse s orrage, bu narcon s uncommon because e area aso receves sudden and s caracerzed by severe dyspnea, cyanoss, and sock, bood roug an nac bronca crcuaon (dua crcuaon). oowed by sezures and coma. he paogeness nvoves acva-    Lodgng of embo n te sma end-arteroar pumonar y brances on o componens o e nnae mmune sysem and coaguaon, oten resus n narcon, parcuary n ndvduas n wom oxy- raer an mecanca obsrucon. I e paen sur vves e n- genaon o e ung s compromsed by congesve ear aure. a crss, dssemnaed nravascuar coaguaon (Caper 9) oten    Mupe sma embo occurrng over me may obsruc a suicen deveops secondar y o e reease o rombogenc subsances n poron o e pumonar y vascuar bed o cause pumonar y yper- amnoc lud. enson and rg venrcuar ear aure (cor pumonae).    Ar embosm. Gas bubbes wn e crcuaon can coaesce and Rarey, an embous passes roug an ara or venrcuar deec obsruc vascuar low, causng dsa scemc njur y. Gas may be and eners e sysemc crcuaon, were  may cause narcs by nroduced no e vascuaure accdenay durng surgca, obse- odgng n end-arera vascuar beds n e bran (sroke) or esewere rc, or aparoscopc procedures; oowng a severe ces wa njur y ; (paradoxca embosm). or as a consequence o sudden decreases n e amosperc pres- sure (e.g., wen dvers surace oo rapdy, dssoved nrogen comes Systemic Thromboembolism ou o souon, ormng gas bubbes n e bood and e ssues, a he mos common source o sysemc romboembo s e ear condon known as e bends). (80%), oowed by aerosceroc aorc esons, aorc aneur ysms, vavuar vegeaons, and DVTs (by paradoxca embozaon). Mos INFARCTION An infarct is an area of ischemic necrosis caused by occlusion of the vascular supply to the affected tissue; infarction is a common and important cause of clinical disease. Arera romboembosm underes e vas majory o narcons. Venous romboss can cause narcon, bu more commony, ere s smpy congeson, as coaera cannes open rapdy and resore e are- ra nlow. Inarcs caused by venous romboss occur n organs w a snge eferen ven (e.g., ess or ovary) and ypcay sem rom a mecan- ca probem (e.g., wsng o a esce, eadng o venous obsrucon). No a vascuar occusons ead o narcon. Deermnans o weer narcon occurs ncude e oowng:    Anaomy o he vascuar suppy. he presence or absence o an aer- nave bood suppy s e mos mporan acor n deermnng weer occuson o an ndvdua vesse causes damage. Tssues w dua bood suppes (ung, ver, and and and orearm) are ressan o narcon, wereas ose w end-arera crcuaons Fig. 3.10 Embolus derived from a lower-extremity deep venous throm- (ear, kdney, and speen) are key o narc. bus lodged in a pulmonary artery branch. 38 CHAPTER 3 Hemodynamic Disorders, Thromboembolism, and Shock    Rate of occuson. Sowy deveopng occusons are ess key o cause narcon due o e deveopmen o coaera crcuaons.    Ceuar vunerabty to ypoxa. Ces range n er suscepby o damage rom vascuar occuson: Neurons de ater ony 3 o 4 mnues, myocarda ces can as or 20 o 30 mnues, and bro- bass reman vabe ater many ours o scema. Morphology. Inarcs may be eer red (emorragc) or we (anemc) and may be eer sepc or band. Re d narcts (Fg. 3.11A) occur w venous occusons (as n ovaran orson); n ssues w coaera bood suppes (e.g., e ung); and oow- ng reesabsmen o low ater narcon as occurred (e.g., ater angopasy o an arera obsr ucon). Whte narcts occur w arera occusons n organs w end-arera crcuaons Fig. 3.12 Remote kidney infarct, now replaced by a large fibrotic scar. (e.g., ear, speen, and kdney) (Fg. 3.11B). Inarcs end o be wedge saped, w e occuded vesse a e apex and e organ exrnsc compresson (cardac amponade) (see Caper 8), or ou- perper y ormng e base (Fg. 3.11A); wen e base s a serosa low obsrucon (e.g., pumonar y embosm). surace, ere s oten an overyng brnous exudae.    Hypovoemc sock resus rom oss o bood or pasma voume In mos  ssues, n arc s d sp ay c o agu  a ve ne c ros s (s e e (e.g., due o emorrage or lud oss rom severe burns). C aper 1). W n a e w ours , an  n   am maor y resp ons e    S eptc sock s rggered by mcroba necons and s assocaed de veops a ong  e marg  ns o  n  arc  s;  e es  on s usu a  y we  w e sysemc nlammaor y response syndrome (SIRS). In add- de ne d w  n 1 o 2 d ay s. In   amma  on s o owe d by re p a r, on o mcrobes, SIRS may be rggered by severe burns, rauma, b eg n nng n  e pres er ve d marg  ns (s ee C aper 2). Mos and pancreas. he paogeness o sepc sock s dscussed aer. narc s are u  maey rep ace d by s c ar  ssue (Fg. 3.12). Te    Neurogenc sock resus rom e oss o vascuar one, as may bran s an excep on o  es e ge nera  za  ons , as s cem  c  ssue occur oowng spna cord njur y. njur y n  e CNS resu s n   quea c  ve ne c ros s o owe d by g  -    Anapyactc sock resus rom sysemc vasodaon and ncreased oss (s e e Caper 17). vascuar permeaby a s rggered by mmunogobun E–med- Sepc narcs occur wen neced cardac vave vegeaons aed mmedae ypersensvy reacons (see Caper 4). emboze or wen mcrobes seed necroc ssue. In ese cases, e narc s convered no an abscess, w a greaer nlammaor y Pathogeness. Sock, regardess o s cause, as ceran common ea- response and eang by organzaon and bross (see Caper 2). ures. I s a progressve dsorder a eads o dea  e underyng probem s no correced. Sock ends o evove roug sages, excep n e seng o massve njur y (e.g., exsangunaon rom a rupured aorc aneur ysm). hese sages are bes documened n ypovoemc sock bu are seen n oer ypes, as we:    Ina nonprogressve stage: relex compensaor y mecansms are acvaed and va organ peruson s mananed    Progressve stage: ssue ypoperuson occurs, w worsenng cr- cuaor y and meaboc derangemens    Irreversbe stage, n wc ceuar and ssue njur y s so severe a even  e emodynamc deecs are correced, sur vva s no pos- sbe In e eary nonprogressve pase, neura and ormona eedback oops manan e cardac oupu and bood pressure by ncreasng e ear rae, consrcng e areroes (n ypovoemc and cardo- A B genc sock), and decreasng e urne oupu. C oronar y and cerebra Fig. 3.11 Red and white infarcts. (A) Hemorrhagic, roughly wedge- vesses are ess sensve o sympaec sgnas and manan a rea- shaped pulmonary infarct (red infarct). (B) Sharply demarcated pale vey norma caber, bood low, and oxygen dever y. hus, bood s infarct in the spleen (white infarct). suned away rom e skn o e va organs suc as e ear and e bran. Wou correcon o e underyng cause, sock proceeds o e SHOCK progressve pase, caracerzed by wdespread ssue ypoxa. Due o a perssen oxygen dec, ces are orced o rey on anaerobc gyco- Shock is a state in which diminished cardiac output or effective yss nsead o aerobc respraon, causng acc acdoss. he owered circulating volume causes a fall in blood pressure, resulting in ssue pH buns e vasomoor response; as a resu, areroes dae diminished tissue perfusion and consequent cellular hypoxia. and bood poos n e mcrocrcuaon, worsenng e cardac ou- Proonged sock evenuay eads o rreversbe ssue njur y and s pu, owerng bood pressure, and pung endoea ces a rsk or oten aa. Is causes a no severa caegores (Tabe 3.3): anoxc njur y. Endoea dysuncon en ses e sage or e deve-    Cardogenc sock resus rom cardac pump aure. I may be opmen o wdespread ssue edema and dssemnaed nravascuar caused by myocarda damage (narcon), venrcuar arrymas,  CHAPTER 3 Hemodynamic Disorders, Thromboembolism, and Shock 38.e1 Supplemental eFig. 3.2 Bone marrow embolus in the pulmonary circulation. The cellular elements on the left side of the embolus are hematopoietic cells, whereas the cleared vacuoles represent marrow Supplemental eFig. 3.3 Amniotic fluid embolism. Two small pulmo- fat. The relatively uniform red area on the right of the embolus is an nary arterioles are packed with laminated swirls of fetal squamous cells. early organizing thrombus. There is marked edema and congestion. Elsewhere the lung contained small organizing thrombi consistent with disseminated intravascular coagulation. (Courtesy Dr. Beth Schwartz, Baltimore, MD.)  CHAPTER 3 Hemodynamic Disorders, Thromboembolism, and Shock 39 Table 3.3 Major Types of Shock Type of Shock Clinical Examples Principal Pathogenic Mechanisms Cardiogenic Myocardial infarction Failure of myocardial pump resulting from intrinsic myocardial Ventricular rupture damage, extrinsic pressure, or obstruction to outflow Arrhythmia Cardiac tamponade Pulmonary embolism Hypovolemic Hemorrhage Inadequate blood or plasma volume Fluid loss (e.g., vomiting, diarrhea, burns) Septic Overwhelming microbial infections Activation of cytokine cascades; endothelial activation/injury; peripheral vasodilation and pooling of blood; leukocyte-induced damage; disseminated intravascular coagulation coaguaon, bo o wc may urer compromse e ssue per- Pathogeness. Sepc sock s rggered by consuens o mcrobes uson. W wdespread ssue ypoxa, va organs are afeced and (mos commony, gram-posve bacera, oowed by gram-negave begn o a. bacera and ung) a acvae e nnae mmune sysem (.e., mac- In e absence o approprae ner venon or n severe cases, e ropages, neurops, dendrc ces, endoea ces, and soube myocarda conrace uncon worsens, pary owng o ncreased componens suc as compemen). hese ces and acors recognze nrc oxde syness. Progresson o rena aure occurs because o and are acvaed by mcroba paogen–assocaed moecuar paerns rena scema (see Caper 11). he downward spra oten cumnaes (PAMPs). Foowng acvaon, a number o nlammaor y responses n dea. ensue a, wen massve or wdespread, nerac n a compex, ncom- peey undersood ason o produce sepc sock and muorgan dysuncon (Fg. 3.13). Facors beeved o pay major roes n e paopysoog y o sepc sock ncude e oowng: Morphology. he efecs o sock on ces and ssues resembe    Inf  ammator y resp on s es. PA M Ps a c  v ae  n   am m aor y ose o ypoxc njur y (see Caper 1) and are caused by a comb- re sp ons e s by e ng ag  ng re c e pors on  n n ae  m mu n e ce s, su c naon o ypoperuson and mcrovascuar romboss. Any organ as To - ke rece ptor s (s ee C  ape r 2), w   c re c o g n  z e a os o may be afeced; e bran, ear, kdneys, adrenas, and gasrones- m  c rob e - d e r ve d PA M Ps. Ac  v ae d  n n ae  m mu n e ce s pro - na rac are mos commony nvoved. Fbrn romb are ready du c e c y ok  n e s su c as u m or n e c ro s  s  a c or (TNF) an d o  e r vsuazed n kdney gomeru bu may be ound rougou e pro n   am m aor y m e d  aors   a  n du c e e n d o  e   a  ce s ( an d body. he ungs are ressan o ypoxc njur y n ypovoemc o  e r ce  yp es) o upre g u  ae a d  e s  on m o e c u  e e x pre s s  on sock occurrng ater emorrage, bu sepss and rauma oten an d  ur  er s  mu  ae c y ok  n e an d c e m ok  n e pro du c   on. Te precpae dfuse alveolar damage and acue respraor y dsress c omp e m e n cas cade s a s o a c  v ae d by m  c rob a  c omp on e n s , syndrome (see Caper 10). Excep or rreversbe neurona and b o  d  re c  y an d   rou g   e proe oy   c a c  v  y o p a s m  n , cardomyocye oss, afeced ssues can recover compeey  e re su   ng n  e pro du c   on o an apy  aox  ns (C3a, C5a), c e - paen sur vves. m o a c   c  r ag m e n s (C5a), an d op s on  ns (C3b), a o w   c c on r  bue o  e pro n   am m aor y s  ae.    Endotea actvaton and njur y. Inlammaor y cyoknes oosen Clncal Features. he manesaons o sock depend on e precp- endoea ce g juncons, resung n e accumuaon o ang nsu. In ypovoemc and cardogenc sock, paens exb proen-rc edema a ms nuren dever y and wase remova ypoenson, a weak rapd puse, acypnea, and coo, cammy, cya- rougou e body. Acvaed endoeum aso produces nrc noc skn. By conras, n sepc sock, e skn may be warm and oxde and oer vasoacve nlammaor y medaors, wc may lused due o perpera vasodaon. he prmar y na rea o e conrbue o vascuar smoo musce reaxaon and sysemc s e rggerng even (e.g., myocarda narcon, severe emorrage, ypoenson. bacera necon). However, secondar y cardac, cerebra, rena, and    Inducton of a procoaguant state. Mcroba componens can ac- pumonar y canges rapdy aggravae e suaon. vae coaguaon drecy roug acor XII and ndrecy roug he prognoss vares w e orgn o sock and s duraon. More aered endoea uncon. Moreover, sepss aers e expresson an 90% o young, oer wse eay paens w ypovoemc sock o many acors so as o avor coaguaon. Pronlammaor y cyo- sur vve w approprae managemen; by comparson, sepc or car- knes ncrease ssue acor producon by monocyes (and poss- dogenc sock s assocaed w subsanay worse oucomes, even by endoea ces) and decrease e producon o endoea w sae-o-e-ar care. ancoaguan acors (e.g., rombomodun and proen C). Bood low n sma vesses decreases, producng sass and dmnsng Septic Shock e wasou o acvaed coaguaon acors. hese derangemens In e Uned Saes, ere are more an 750,000 cases per year o cause dssemnaed nravascuar coaguaon (see Caper 9) n sepc sock, wc s responsbe or approxmaey 2% o a osp- up o a o sepc paens. Tssue peruson s urer compro- a admssons. Despe mprovemens n care, 20% o 30% o afeced msed by e sysemc acvaon o rombn and e deposon paens de. o brn-rc romb n sma vesses. In u-bown dssemnaed 40 CHAPTER 3 Hemodynamic Disorders, Thromboembolism, and Shock Microbial products (PAMPs) Neutrophil and monocyte activation Complement Endothelial Factor XII activation activation C3a C3 TNF, IL-1, HMGB1 Direct and indirect Cytokines and cytokine-like mediators Procoagulant Antifibrinolytic IL-6, IL-8, NO, PAF, IL-10, apoptosis, reactive oxygen species, sTNFR TF PAI-1 etc. TFPI, thrombomodulin, Secondar y antiinflammator y protein C mediators VASODILATION MICROVASCULAR SYSTEMIC INCREASED PERMEABILITY IMMUNOSUPPRESSION THROMBOSIS (DIC) EFFECTS DECREASED PERFUSION Fever, diminished myocardial contractility, metabolic abnor malities TISSUE ISCHEMIA Adrenal insufficiency MULTIORGAN FAILURE Fig. 3.13 Major pathogenic pathways in septic shock. Microbial products activate endothelial cells and cellular and humoral elements of the innate immune system, initiating a cascade of events that lead to end-stage multiorgan failure. Additional details are provided in the text. DIC, Disseminated intravascular coagulation; NO, nitric oxide; PAI-1, plasminogen activator inhibitor-1; sTNFR, soluble TNF receptor; TF, tissue factor; TFPI, tissue factor pathway inhibitor; TNF, tumor necrosis factor. nravascuar coaguaon, e consumpon o coaguaon ac- nurens o ssues. Hg cyokne eves and secondar y medaors ors and paees causes decences o ese acors, resung n a dmns myocarda conracy and cardac oupu, urer com- supermposed beedng dsorder a may be e reaenng. promsng ssue peruson. Increased vascuar permeaby and    Metaboc abnormates. S epc paens exb nsun ressance endoea njur y may ead o e acue respraor y dsress syn- and ypergycema. Cyoknes suc as umor necross acor and drome (see Caper 10). Umaey, ese acors may conspre o IL-1, sress-nduced ormones suc as gucagon, grow or- cause e aure o mupe organs, parcuary e kdneys, ver, mone, and gucocorcods, and caecoamnes a drve guco- ungs, and ear, cumnang n dea. neogeness. A e same me, e pronlammaor y c yoknes he mupcy o acors and e compexy o e neracons suppress nsun reease and promoe nsun ressance n e ver a undere sepss precude erapeuc ner venon w anagonss and oer ssues. I severe, ceuar ypoxa and dmnsed ox- o specc medaors, suc as umor necross acor. he sandard o dave pospor yaon ead o ncreased acae producon and care remans anbocs o rea e underyng necon and nrave- acc acdoss. nous luds, pressors, and suppemena oxygen o manan e bood    Organ dysfuncton. Sysemc ypoenson, nersa edema, pressure and m ssue ypoxa. Even n e bes ceners, sepc sock and sma-vesse romboss decrease e dever y o oxygen and remans a daunng cnca caenge.  4 Diseases of the Immune System O U T L I N E Hypersensitivity Disorders, 41 Rejection of Transplants, 52 Immediate (Type I) Hypersensitivity, 42 Immune Responses to Organ Allografts, 53 Antibody-Mediated (Type II) Hypersensitivity, 44 Mechanisms of Rejection of Solid-Organ Allografts, 53 Immune Complex–Mediated (Type III) Hypersensitivity, 47 Hematopoietic Stem Cell Transplantation, 54 T Cell-Mediated (Type IV) Hypersensitivity, 47 Immunodeficiency Disorders, 56 Autoimmune Diseases, 49 Primary (Congenital) Immunodeficiencies, 56 Mechanisms of Autoimmunity, 49 Acquired Immunodeficiency Syndrome, 58 Systemic Lupus Erythematosus (SLE), 50 Human Immunodeficiency Virus: Structure and Life Cycle, 58 Systemic Sclerosis (Scleroderma), 51 Amyloidosis, 59 Sjögren Syndrome, 51 he mmune sysem proecs us agans necons and cancers by wo    C e-medated mmunty medaed by T ces. T ces are acvaed ypes o mecansms: nnae mmuny and adapve mmuny. by proen angens dspayed by angen-presenng ces (APCs), Innate mmunty s e rapd response o necons medaed by and requre repea angen smuaon o perorm er unc- ces and pasma proens a are aways presen and ready o aack ons. Two major ypes o T ces, CD4+ and CD8+, uncon d- (ence, nnate). he prncpa ces o nnae mmuny are myeod ces, ereny n os deense and paoogc reacons. CD4+ eper ncudng macropages, neurops, and dendrc ces, bu ympo- T ces secree c yoknes a acvae macropages o desroy cyes, epea ces, and oer ce ypes aso possess nrnsc deense pagoc yosed mcrobes, ep B ces o make poen anbodes, mecansms. hese ces express recepors suc as To-ke recepors and smuae nlammaon. Heper T ces conss o severa sub- a recognze mcroba producs and producs o necroc ces. hese ses a produce dferen c yoknes and nduce dferen ypes recepors, unke e angen recepors o T and B ympocyes, are o nlammaor y reacons: h1 ces acvae macropages, h2 no paogen specc and ave med dversy. ey are rggered by ces acvae eosnops, and h17 ces smuae neurop-rc moecues sared by many paogens (paogen-assocaed moecuar nlammaon. CD8+ c yooxc T ympoc yes (CTLs) k neced paerns [PAMPs]) and subsances reeased rom damaged ces (dam- and ransormed ces. age-assocaed moecuar paerns [DAMPs]). e major reacon o Aoug e mmune sysem evoved as a proecve orce, a mes nnae mmuny s acue nlammaon (see Caper 2).  can go awry and cause ssue njury and cnca dsease. In s cap- Adaptve mmunty s e more poweru and specazed se o er, we dscuss e mos mporan paoogc reacons and dseases a responses medaed by T and B ympoc yes. hese ces express spe- are caused by mmune responses, many adapve mmune responses, as cc and gy dverse recepors or angens. E ac T and B ym- we as decences o e mmune sysem and er consequences. poc ye and s cona progeny express a unque recepor and, ence, ave a unque speccy. he dversy o e recepors s creaed by HYPERSENSITIVITY DISORDERS rearrangemens o angen-recepor genes a occur durng e ma- uraon o e ympoc yes. hus, e presence o rearranged an- Persistent, misdirected, or inadequately regulated immune reac- gen-recepor genes s a reabe marker o T and B ympoc yes and tions against a variety of antigens may cause tissue injury. o umors derved rom ese ces. Lympoc yes are normay sen An ndvdua wo as been exposed o and reacs agans an angen and are acvaed by (adap o) angens (ence, e erm adapve s sad o be senszed, so njurous mmune reacons are caed yper- mmuny). Foowng acvaon, e ympoc yes produce efecor senstvty reactons. Hypersensvy dseases end o be cronc and ces a possess mecansms a uncon o emnae mcrobes dicu o conro, and are ereore mporan cnca probems. hese and umor ces. hese mecansms ncude: dseases may be caused by reacons o ree man ypes o angens.    Humora mmunty medaed by anbodes, wc are produced    R eactons aganst sef antgens are caed auommuny, and e by B ces and er dferenaed progeny, pasma ces. Anbodes dseases ey cause are autommune dseases. As we sa dscuss neuraze mcrobes, opsonze em or pagocyoss, and acvae aer, ndvduas are normay oeran o er own (se ) an- e compemen sysem. gens, and auommuny resus wen se-oerance breaks down. 41