Robbins Essential Pathology: Hematopoietic and Lymphoid Systems (PDF)
Document Details
Uploaded by CleanlyBoston
Mansoura
Tags
Summary
This chapter from Robbins Essential Pathology discusses bleeding disorders, specifically focusing on vascular fragility, platelet dysfunction, and coagulation factor deficiencies. It also covers causes of thrombocytopenia, including decreased platelet production, increased platelet destruction, and sequestration. The text provides a comprehensive review of these conditions.
Full Transcript
CHAPTER 9 Hematopoietic and Lymphoid Systems 159 Table 9.8 Bleeding Disorders...
CHAPTER 9 Hematopoietic and Lymphoid Systems 159 Table 9.8 Bleeding Disorders Mechanism Causes Clinical Features Vascular fragility Vitamin C deficiency (scurvy) Ecchymoses, skin and mucous mem- Systemic amyloidosis branes Chronic glucocorticoid use Inherited connective tissue disorders Vasculitis Platelet dysfunction Thrombocytopenia Petechial bleeding, mucosae and skin Immune-mediated Epistaxis Consumptive (DIC, HUS, TTP) Prolonged immediate bleeding from Marrow underproduction (tumors, other infiltrative disorders, aplastic minor trauma anemia) Menorrhagia Qualitative defects Drugs (aspirin, other platelet inhibitors) Myeloid neoplasms Inherited defects (von Willebrand disease, Glanzmann thrombasthenia, Bernard-Soulier syndrome) Coagulation factor Inherited Hemorrhages in sites subject to mechani- deficiencies Hemophilia A cal trauma (e.g., joints) Hemophilia B Delayed bleeding after surgery (e.g., Acquired circumcision) Underproduction (vitamin K deficiency, liver disease) Bleeding in deep soft tissues (e.g., psoas Factor inhibitors (antibodies, drugs) muscle) Consumptive (DIC) Table 9.9 Causes of Thrombocytopenia Addona more specazed ess are used o measure e eves o specc cong acors and brn sp producs or o assess e pres- Decreased Production of Platelets ence o crcuang ancoaguans. Generalized Bone Marrow Dysfunction Abnormaes o vesses a ead o beedng ncude a range o Aplastic anemia: congenital and acquired msceaneous, uncommon dsorders, wereas dsorders o paees Marrow infiltration: leukemia, disseminated and coaguaon acors are reavey common. cancer Selective Impairment of Platelet Production Thrombocytopenia Drug-induced: alcohol, thiazides, cytotoxic drugs hrombocyopena s dened as a paee coun o ess an 150,000/μL. Infections: measles, HIV infection Excessve posraumac beedng s seen ony wen e paee couns Ineffective Megakaryocytopoiesis are reduced o 20,000 o 50,000/μL, and sponaneous beedng s unkey un couns a beow 5000/μL. Beedng ypcay occurs Megaloblastic anemia rom sma, superca bood vesses and produces peecae or arge Decreased Platelet Survival eccymoses n e skn, e mucous membranes o e gasrones- Immunologic Destruction na and urnar y racs, and oer ses. he mos eared compcaon Autoimmune: o rombocyopena s emorrage no e cenra ner vous sysem, Primary: immune thrombocytopenic purpura wc s uncommon bu may be aa. Secondary: B-cell tumors (e.g., chronic lymphocytic Maj or c aus es o romb o c yop en a are se d n Tabe 9.9. C n - leukemia); autoimmune disorders (systemic lupus erythematosus); c a y mp or an romb o c yop en a may be c aus e d by re duc e d infections (infectious mononucleosis, HIV) pro duc on or ncre as e d d es r uc on o p aee s. Sp enome ga y Isoimmune: posttransfusion and neonatal depress es p aee couns b e c aus e o e s e qu es ra on o p aee s Drug-associated: quinidine, heparin, sulfa compounds bu n and o s e d o es no c aus e c n c a y s g n c an romb o- c yop en a. R e duce d pro duc on s ge nera y due o a probem w Nonimmunologic Destruction emaop oess a a s o a e c s re d ce and g ranu o c ye pro duc on. Disseminated intravascular coagulation In con ras, ncre as e d d es r uc on o p aee s may be s e en as an s o - Hemolytic-uremic syndrome ae d abnor ma y n s e ver a ds orde rs a mer a br e ds c uss on. Thrombotic thrombocytopenic purpura Microangiopathic hemolytic anemia Immune Thrombocytopenic Purpura Dengue fever Immune rombocyopenic purpura (ITP) is an auoimmune disease Sequestration caused by anibodies a bind paee surface proeins, eading o Hypersplenism opsonizaion of e paees and eir remova from e circuaion Dilutional by macropages. Multiple transfusions (e.g., for massive blood loss) he dsease as wo cnca subypes. Acue ITP s a se-med HIV, human immunodeficiency virus. orm seen mosy n cdren ater vra necons. Cronc ITP s a reavey common dsorder a mos oten afecs women beween 160 CHAPTER 9 Hematopoietic and Lymphoid Systems e ages o 20 and 40 years. he speen s an mporan se o an- Coagulation Disorders paee anbody producon and e major se o desrucon o e Coagulation disorders result from either congenital or acquired IgG-coaed paees, so spenecomy s beneca. Cronc ITP s an deciencies of protein factors that are required for clotting. soaed dsorder a mus be dsngused rom secondar y ITP due Acqured decences are more common and are mos oten caused by : o oer condons (e.g., sysemc upus er yemaosus, drug exposure, Vtamn K deicency. hs usuay occurs n e seng o HIV necon, and B-ce magnances). broad-specrum anboc erapy, nesna maabsorpon, or he onse o cronc ITP s nsdous. Common ndngs ncude mpared nuron, and resus n nadequae syness o pro- peecae, easy brusng, epsaxs, gum beedng, and emorrages ater rombn and cong acors VII, IX, and X and a severe coagua- mnor rauma. Serous nracerebra or subaracnod emorrages are on deec. Wararn s an ancoaguan drug a acs by nbng rare, bu occur. he dagnoss ress on e cnca eaures, e presence e syness o vamn K-dependen acors. o rombocyopena, and e response o erapy. Mos paens are Lver dsease. he ver syneszes severa coaguaon acors and rs reaed w gucocorcods, wc nb macropage uncon aso removes many acvaed coaguaon acors rom e crcu- and rapdy correc e paee coun and somemes produce susaned aon; us, epac parencyma dseases are common causes o responses, even ater dsconnuance. For oers, spenecomy, an–B- compex coaguaon dsorders. ce erapes (e.g., an-CD20 anbodes), and rombopoen-ke Dssemnated ntravascuar coaguaton (DIC; dscussed aer) oten drugs are oten efecve a conrong e rombocyopena. eads o decences o mupe acors. Autoantbodes agans coaguaon acors cause acqured decen- Heparin-Induced Thrombocytopenia ces med o a snge acor. hs speca ype o drug-nduced rombocyopena mers a bre Heredar y decences o many coaguaon acors aso ave been menon because o s cnca mporance. Moderae o severe rom- dened. O ese, ony von Webrand dsease, emopa A, and bocyopena deveops n 3% o 5% o paens ater 1 o 2 weeks o emopa B are suceny common o warran urer consderaon. reamen w eparn. I s caused by IgG anbodes a bnd o Von Willebrand Disease paee acor 4 on paee membranes n a eparn-dependen as- on. Anbody bndng acvaes paees and nduces er aggregaon, Von Willebrand disease is a bleeding disorder caused by qualita- ereby exacerbang romboss, e condon a eparn s used o tive or quantitative defects in von Willebrand factor. rea. Bo venous and arera romboses occur, even n e seng o Von Webrand dsease s caracerzed by sponaneous beedng marked rombocyopena, and may cause severe morbdy (e.g., oss rom mucous membranes, excessve beedng ater dena procedures o mbs) and dea. Cessaon o eparn erapy breaks e cyce o or surger y, and menorraga I s more prevaen n persons o Euro- paee acvaon and consumpon. pean descen and s beeved o afec approxmaey 1% o peope n e Uned Saes, makng e mos common nered beedng dsorder. Thrombotic Microangiopathies Von Webrand acor (vWF) s many syneszed n endoea he erm trombotc mcroangopates encompasses a specrum o cn- ces and megakar yocyes and exss n e pasma as arge mumers o ca syndromes a ncude romboc rombocyopenc purpura (TTP) up o 20 MDa n weg (Fg. 9.23). I aso s ound n e subendoe- and emoyc-uremc syndrome (HUS). her causes are dferen, bu a um, were bnds o coagen. vWF as wo major uncons: are caracerzed by abnorma paee acvaon and deposon o pae- vWF bnds to pateet gycoprotens, aowng vWF o ser ve as a e-rc romb n e mcrocrcuaon, eadng o rombocyopena moecuar “gue” beween subendoea coagen and paees o- and anema. In conras o DIC, acvaon o coaguaon acors s no a owng endoea damage (see Fg. 9.23). promnen eaure o HUS or TTP; consequeny, e PT and PTT are usu- vWF bnds factor VIII, a coacor or acor IX, ncreasng s a- ay norma or ony sgy deranged. Because bo dsorders promneny e n e crcuaon and enancng dever y o acor VIII o ses nvove e kdney, ey are dscussed n Caper 11 o prmar y emosass. Endothelium Collagen Factor VIII X Xa Clotting vWF Activated, aggregated cascade Circulating vWF platelets with Factor VIII Platelet Fibrinogen GpIIb/IIIa GpIb Platelet Subendothelial vWF Endothelial defect Fig. 9.23 Structure and function of factor VIII–von Willebrand factor (vWF) complex. Factor VIII and vWF circulate as a complex. vWF also is present in the subendothelial matrix of normal blood vessels. Factor VIII takes part in the coagulation cascade by activating factor X by means of factor IX (not shown). vWF causes adhesion of platelets to subendothelial collagen, primarily through the glycoprotein Ib (GpIb) platelet receptor. CHAPTER 9 Hematopoietic and Lymphoid Systems 161 Von Webrand dsease s us assocaed w deecs n bo as a “oregn” angen. hese dcu-o-rea paens may bene rom paee uncon and coaguaon; ony e paee deec produces erapy usng a bspecc anbody a cross-nks acor IX o acor X, cnca ndngs, excep n rare paens w omozygous von We- greay dmnsng e pysoogc requremen or acor VIII. brand dsease wo ave severe acor VIII decency. Hemophilia B–Factor IX Deficiency he cassc and mos common varan o von Webrand dsease s an auosoma domnan dsorder w reduced crcuang vWF and a Severe acor IX decency s an X-nked dsorder a s cncay measurabe bu cncay nsgncan decrease n acor VIII eves a ndsngusabe rom emopa A bu muc ess common. he proongs e PTT. Less common varees o von Webrand dsease ave dagnoss s made usng specc assays o acor IX. I s reaed by nu- muaons causng quaave deecs n vWF a ead o abnormay son o recombnan acor IX. arge or sma vWF mumers, prevenng norma prmary emosass. Disseminated Intravascular Coagulation he dagnoss s reaced by measurng e quany, sze, and uncon o vWF. vWF uncon s assessed usng e rstocetn pateet aggutnaton Disseminated intravascular coagulation is a condition in which test. Rsocen “acvaes” e bndng o vWF o paee gycoproens, cre- excessive activation of clotting results in the formation of thrombi ang nerpaee brdges a cause paees o cump (aggunaon), an in many tissues and secondary deciencies of platelets and coagu- easy quaned even a serves as a useu assay o vWF uncon. lation factors. Dssemnaed nravascuar coaguaon (DIC) occurs as a comp- Hemophilia A caon o a wde varey o dsorders. DIC can gve rse o eer ssue Hemophilia A, the most common hereditary cause of serious bleed- ypoxa and mcronarcs caused by mcroromb or o a beedng ing, is an X-linked disorder caused by deciency of factor VIII. dsorder reaed o depeon o e eemens requred or emosass Amos a afeced ndvduas are maes. Approxmaey 30% o (ence e erm consumptve coaguopaty). cases are caused by new muaons; n e remander, ere s a posve amy sor y. Severe emopa A s obser ved n peope w marked Pathogeness. Cong can be naed by eer e exrnsc paway, decences o acor VIII (acvy eves < 1% o norma). Mder de- wc s acvaed by ssue acor ; or e nrnsc paway, wc s cences may ony manes ater rauma or oer emosac sresses. acvaed wen acor XII neracs w coagen or oer negavey he var yng degrees o acor VIII decency are due o e exsence o carged subsances. Bo paways generae rombn, wc ceaves many dferen causave muaons. brnogen o orm a brn co. Cong s normay med o e se In sympomac cases, ere s a endency oward easy brusng and o njur y by a number o acors (see Caper 3). massve emorrage ater rauma or surgca procedures In addon, DIC may be rggered by (1) excessve reease o ssue acor or “sponaneous” emorrages requeny are encounered n ssues a are oer rombopasc subsances no e crcuaon or (2) wde- subjec o mecanca sress, parcuary jons, were recurren beeds spread endoea ce damage (Fg. 9.24). S evere endoea ce (emartroses) ead o progressve deormes a can be crppng. Beeds njur y exposes subendoea ssue acor and coagen. Even md no deep sot ssues (e.g., musces) and e bran aso may occur. endoea damage can uneas procoaguan acvy by smuang he dagnoss s suspeced based on a caracersc beedng sory ssue acor expresson we suppressng expresson o ancoagu- n an nan or young cd and e dencaon o a proonged PTT, an acors (e.g., rombomodun). Endoea njur y as a cenra and s conrmed w specc acor assays. Hemopa A s usuay roe n sysemc nlammaor y response syndrome (SIRS) rggered reaed w acor VIII nusons. In approxmaey 15% o ose w by sepss and oer sysemc nsus (see Caper 3); DIC s a re- severe emopa A, repacemen erapy s compcaed by e deveop- quen compcaon o SIRS. Dsorders assocaed w DIC are sed men o neurazng anbodes agans acor VIII, wc s recognzed n Tabe 9.10. O ese, DIC s mos oten assocaed w sepss, Massive tissue Endothelial Sepsis destruction injury Release of tissue factor Platelet aggregation Widespread microvascular thrombosis Activation of plasmin Microangiopathic Vascular hemolytic anemia occlusion Consumption of Proteolysis of Ischemic tissue Fibrinolysis clotting factors clotting factors damage and platelets Fibrin split products Bleeding Inhibition of thrombin, platelet aggregation, and fibrin polymerization Fig. 9.24 Pathophysiology of disseminated intravascular coagulation. 162 CHAPTER 9 Hematopoietic and Lymphoid Systems Table 9.10 Major Disorders Associated with Table 9.11 Causes of Splenomegaly Disseminated Intravascular Coagulation Massive Splenomegaly (weight >1000 g) Obstetric Complications Myeloproliferative neoplasms (chronic myeloid leukemia, primary Abruptio placentae myelofibrosis) Retained dead fetus Lymphoid leukemias (chronic lymphocytic leukemia and hairy cell Septic abortion leukemia) Amniotic fluid embolism Lymphoma Toxemia Infectious diseases (e.g., malaria) Storage diseases (e.g., Gaucher disease) Infections Moderate splenomegaly (weight 500 to 1000 g) Sepsis (gram-negative and gram-positive) Meningococcemia Chronic congestive splenomegaly (portal hypertension or splenic Rocky Mountain spotted fever vein obstruction) Histoplasmosis Acute leukemias Aspergillosis Hemolytic anemias (hereditary spherocytosis, thalassemia, immu- nohemolytic anemia) Neoplasms Amyloidosis Adenocarcinomas of pancreas, prostate, lung, and stomach Niemann-Pick disease Acute promyelocytic leukemia Chronic infections (tuberculosis) Massive Tissue Injury Sarcoidosis Trauma Mild splenomegaly (weight < 500 g) Burns Infectious mononucleosis Extensive surgery Miscellaneous disorders (sepsis, systemic lupus erythematosus) Miscellaneous Acute intravascular hemolysis, snakebite, giant hemangioma, shock, heat stroke, vasculitis, aortic aneurysm, liver disease bood, e speen s secondary nvoved by many sysemc dsorders. In vruay a nsances, e speen responds by enargng (speno- obserc compcaons, magnanc y, and major rauma (especay o megay), an aeraon a produces a se o sereoypca sgns and e bran). sympoms. Dsorders may be grouped accordng o e degree o spe- Once naed, DIC as wo consequences: (1) brn deposon n nomegay a ey caracerscay produce (Tabe 9.11). e crcuaon (romboss) and (2) depeon o paees and cong Wen enarged, e speen and s resden macropages oten remove acors w secondar y reease o pasmnogen acvaors, causng a excessve numbers o ormed bood eemens, resung n anema, euko- beedng dsorder a s paradoxcay supermposed on e excessve pena, or rombocyopena; s s reerred o as yperspensm. Paees cong. Pasmn ceaves no ony brn (brnoyss) bu aso acors are parcuary suscepbe o sequesraon n e nersces o e red V and VIII, ereby reducng er concenraon urer. In addon, pup; as a resu, trombocytopena s more prevaen and severe n per- brnoyss creaes brn degradaon producs a nb paee sons w spenomegay an s anema or neuropena. aggregaon, ave anrombn acvy, and mpar brn poymerza- on, a o wc conrbue o beedng. DISORDERS OF THE THYMUS Clncal Features. Dependng on e baance beween cong and beed- he ymus as a cruca roe n T-ce mauraon and s requeny ng endences, e range o cnca manesaons s enormous, rom mere nvoved by T-ce acue ympobasc eukema (T-ALL). he ocus aboraory abnormaes o muorgan aure, crcuaory coapse, and ere s on e wo mos requen (abe s uncommon) dsorders o massve, somemes aa, beedng. In genera, acue DIC (e.g., a assoc- e ymus, ymc yperpasa and ymoma, bo o wc may be aed w necon or obserc compcaons) s domnaed by beedng, assocaed w sysemc auommune dseases. wereas cronc DIC (e.g., as occurs n ose w cancer) more oten causes Thymic Follicular Hyperplasia romboss. Laboraory ess revea rombocyopena, proongaon o e PT and PTT, ncreased brn sp producs, and decreased brnogen. he he mos requen cause o ymc enargemen s ormaon o ympod presence o romb n sma vesses aso creaes sear sress a dsrups red oces and yperpasa o germna cener B ces, wc are no normay ces, producng so-caed mcroangopac emoyc anema. Red ce rag- presen n e ymus. hymc ocuar yperpasa s ound n mos mens caed scsocyes are caracerscay seen n e perpera bood. paens w myastena gravs (see Caper 18) and may occur n oer he prognoss s dcaed by e underyng dsorder and e sever- auommune dseases, suc as sysemc upus eryemaosus and reuma- y o e DIC. Acue DIC s e reaenng and s reaed aggressvey od arrs. Neer e cause o e ymc yperpasa nor s conrbu- w ancoaguans romboss domnaes or by admnsraon o on o e assocaed auommune dsorders s undersood, bu remova o cong acors (res rozen pasma) and paees beedng s e e yperpasc ymus may ead o remance o e myasena. prncpa probem. In conras, cronc DIC s somemes dened Thymoma unexpecedy by aboraor y esng. In eer crcumsance, e ony denve ner venon s reamen o e underyng cause. hymomas are neopasms derved rom ymc epea ces. hey may arse a any age, bu mos occur n mdde-aged adus. hey may be bengn or magnan. Mos ncude varabe numbers o nonneo- DISORDERS OF SPLEEN AND THYMUS pasc mmaure T ces. In abou 30% o cases, ymoma s assocaed w an auommune dsorder (e.g., myasena gravs, sysemc upus SPLENOMEGALY er yemaosus, pure red ce apasa). Remova o e ymoma may Prmar y dsorders o e speen are rare, bu as an mporan com- ead o remance o myasena gravs bu s ess efecve n reang ponen o e nnae and adapve mmune sysem and a er or e oer assocaed dsorders.. 10 Lung and Upper Respiratory Tract O U T L I N E Acute Respiratory Distress Syndrome, 163 Nosocomial Bacterial Pneumonias, 174 Obstructive Lung Diseases, 164 Aspiration Pneumonias, 174 Chronic Obstructive Pulmonary Disease, 165 Lung Abscess, 174 Asthma, 166 Tuberculosis, 175 Bronchiectasis, 168 Community-Acquired Viral Pneumonias, 177 Restrictive Lung Diseases, 168 Fungal Infections, 179 Fibrosing Diseases, 168 Opportunistic Infections, 180 Pneumoconioses, 169 Lung, Pleural, and Upper Airway Tumors, 181 Granulomatous Diseases, 170 Lung Carcinoma, 181 Pulmonary Diseases of Vascular Origin, 171 Carcinoid Tumors, 184 Pulmonary Embolism, Hemorrhage, and Infarction, 171 Malignant Mesothelioma, 184 Pulmonary Hypertension, 172 Nasopharyngeal Carcinoma, 185 Diffuse Alveolar Hemorrhage Syndromes, 172 Carcinoma of the Larynx, 185 Pulmonary Infections, 172 Community-Acquired Bacterial Pneumonias, 173 he ung s anaomcay desgned o repens oxygen and remove sudes. Pumonar y macropages resp ond o e njur y by pro ducng carbon doxde rom e bood. Gas excange depends on a nework pronammaor y medaors (Fg. 10.1) a acvae endoea ces. o capares a e cosey apposed o sac-ke ermna ar spaces Adeson moecues a bnd neurops are upreguaed, eadng caed aveo a are separaed rom e bood by a n ayer com- o sequesraon o e neurops n pumonar y capares. L o cay prsed o epea ces, a sma amoun o exraceuar marx, and pro duced c yoknes as o acvae e neurops, wc reeas e a a ayer o endoea ces. A broad range o dseases nvove e ung, varey o pro ducs (e.g., reacve oxygen sp eces, proeas es) a may ncudng nlammaor y, necous, and neopasc dsorders, many o ur er damage e aveoar epeum and endoeum. wc presen w sgns and sympoms reaed o abnormaes o gas excange. In s caper, we ocus on common dsorders a afec e Morphology. e soogc manesaon o acue respraor y ung and e upper ar ways. dsress syndrome s dfuse alveolar damage. In e acue pase, e ungs are dark red, irm, and eavy. Mcroscopc examnaon ACUTE RESPIRATORY DISTRESS SYNDROME reveas congeson, necross o aveoar epea ces, nersa and nraaveoar edema and emorrage, and (parcuary w Acute respiratory distress syndrome is a disorder in which damage sepss) coecons o neurops n capares. e aveo are oten to alveoli throughout the lungs causes edema and leads to respira- ned by yalne membranes conssng o ibrn-rc edema ud tory failure. mxed w debrs rom necroc epea ces (Fg. 10.2). In e Acue respraor y dsress syndrome afecs approxmaey 190,000 organzng stage, aveoar epeum proeraes o regenerae e paens per year n e Uned Saes and s aso reerred o cncay as aveoar nng. Heang may ead o resouon or o e deveopmen acue ung njury. I s caracerzed by e rapd onse o e-reaenng o ibroc ckenng o e aveoar was. respraor y nsucency, cyanoss, and severe arera ypoxema. Pathogeness. Acue respraor y dsress syndrome may o ccur n Clncal Features. Acue respraor y dsress syndrome usuay deve- asso caon w prmar y pumonar y ds eas es or sysemc nam- ops wn 72 ours o e na nsu. Mos paens requre nu- maor y dsorders. e mos requen rggers are pneumona and baon and mecanca venaon, wc mproves oxygenaon, bu, sepss, oowed by aspraon, se vere rauma, pancreas, and rans- noneeess, approxmaey one rd o paens de, usuay because uson reacons. A o ese dsorders may caus e wdespread njur y o e underyng dsorder (e.g., sepss) or muorgan aure. Mos o aveoar endoea and epea ces, eadng o an accumua- paens wo sur vve recover norma respraor y uncon wn 6 on o edema ud n e aveoar nersum and e ar spaces o 12 mons, bu oers ave cronc respraor y nsucenc y rom and pro ducng a caracersc “weou” o e ungs on magng resdua aveoar ibross. 163 164 CHAPTER 10 Lung and Upper Respiratory Tract NORMAL ALVEOLUS ACUTE LUNG INJURY Bronchial epithelium Sloughed bronchial epithelium Inactivated Necrotic type I cell surfactant Basement membrane Edema fluid Leukotrienes PAF Proteases Alveolar macrophage Cellular debris Surfactant layer TNF IL-1 Alveolus Neutrophil sequestration Fibrin Type I cell and migration into alveolus TNF Hyaline Chemokines Type II cell membrane Interstitium Fibroblast Capillary Procollagen Edema Endothelial cell Injured, swollen endothelial cells Fig. 10.1 The normal alveolus (left) and the injured alveolus in the early phase of acute lung injury and the acute respiratory distress syndrome. Under the influence of proinflammatory cytokines such as IL-8 and IL-1 and tumor necrosis factor (TNF) (released by macrophages), neutrophils are sequestered in the pulmonary microvasculature and then egress into the alveolar space, where they are activated. Activated neutrophils release factors (leukotrienes, reactive oxygen species, proteases, and platelet-activating factor [PAF]) that contribute to local tissue damage, accumulation of edema fluid, surfactant inactivation, and hyaline mem- brane formation. Subsequently, the release of macrophage-derived fibrogenic cytokines such as transforming growth factor- (TGF-) and platelet-derived growth factor (PGDF) stimulate fibroblast growth and collagen deposition associated with the healing phase of injury. (Modified from Ware LB: Pathophysiology of acute lung injury and the acute respiratory distress syndrome, Semin Respir Crit Care Med 27:337, 2006.) OBSTRUCTIVE LUNG DISEASES Cronc dseases a decrease pumonar y gas excange are dvded no (1) obstructve (arway) dsease, caracerzed by an ncrease n ressance o ar low caused by para or compee ar way obsruc- on a any eve, and (2) restrctve dsease, caracerzed by reduced expanson o e ung parencyma and decreased oa ung capacy. In obsrucve dseases, e orced va capacy (FVC) s norma or sgy decreased, wereas e expraor y low rae, usuay measured as e orced expraor y voume a 1 second (FEV ), s sgnicany 1 decreased. us, e rao o FEV o FVC s decreased. By conras, n resrcve dseases (dscussed aer), e FVC s reduced and e exp- raor y ow rae s norma or reduced proporonaey. Hence, e rao o FEV o FVC s near norma. e ree major obsrucve ung dsorders—empysema, cronc broncs, and asma—ave caracersc cnca and paoogc eaures n er prooypca orms (Tabe 10.1). Because empysema and cronc broncs oten coexs o var yng degrees, we w ds- cuss em ogeer under e rubrc o cronc obsrucve pumonar y Fig. 10.2 Acute lung injury and acute respiratory distress syndrome. Diffuse alveolar damage. Some alveoli are collapsed, and others are distended; many are lined by pink hyaline membranes (arrow).
