Robbins Essential Pathology_p191-196.pdf

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 Addona more specazed ess are used o measure e eves o specc cong acors and brn sp producs or o assess e pres- Decreased Production of Platelets ence o crcuang ancoaguans. Generalized Bone Marrow Dysfunction Abnormaes o vesses a ead o beedng ncude a range o Aplastic anemia: congenital and acquired msceaneous, uncommon dsorders, wereas dsorders o paees Marrow infiltration: leukemia, disseminated and coaguaon acors are reavey common. cancer Selective Impairment of Platelet Production Thrombocytopenia Drug-induced: alcohol, thiazides, cytotoxic drugs hrombocyopena s dened as a paee coun o ess an 150,000/μL. Infections: measles, HIV infection Excessve posraumac beedng s seen ony wen e paee couns Ineffective Megakaryocytopoiesis are reduced o 20,000 o 50,000/μL, and sponaneous beedng s unkey un couns a beow 5000/μL. Beedng ypcay occurs Megaloblastic anemia rom sma, superca bood vesses and produces peecae or arge Decreased Platelet Survival eccymoses n e skn, e mucous membranes o e gasrones- Immunologic Destruction na and urnar y racs, and oer ses. he mos eared compcaon Autoimmune: o rombocyopena s emorrage no e cenra ner vous sysem, Primary: immune thrombocytopenic purpura wc s uncommon bu may be aa. Secondary: B-cell tumors (e.g., chronic lymphocytic Maj or c aus es o  romb o c yop en  a are se d n Tabe 9.9. C n - leukemia); autoimmune disorders (systemic lupus erythematosus); c a  y mp or  an  romb o c yop 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 aee  s. Sp enome ga y Isoimmune: posttransfusion and neonatal depress es p aee couns b e c aus e o  e s e qu es ra  on o p aee  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 yop en a. R e duce d pro duc   on s ge nera  y due o a probem w   Nonimmunologic Destruction emaop oess  a a s o a e c s re d ce  and g ranu  o c ye pro duc   on. Disseminated intravascular coagulation In con ras, ncre as e d d es r uc   on o p aee s may be s e en as an s o - Hemolytic-uremic syndrome  ae d abnor ma  y n s e ver a  ds orde rs  a mer  a br  e ds c uss  on. Thrombotic thrombocytopenic purpura Microangiopathic hemolytic anemia Immune Thrombocytopenic Purpura Dengue fever Immune rombocyopenic purpura (ITP) is an auoimmune disease Sequestration caused by anibodies a bind paee surface proeins, eading o Hypersplenism opsonizaion of e paees and eir remova from e circuaion Dilutional by macropages. Multiple transfusions (e.g., for massive blood loss) he dsease as wo cnca subypes. Acue ITP s a se-med HIV, human immunodeficiency virus. orm seen mosy n cdren ater vra necons. Cronc ITP s a reavey common dsorder a mos oten afecs women beween 160 CHAPTER 9 Hematopoietic and Lymphoid Systems e ages o 20 and 40 years. he speen s an mporan se o an- Coagulation Disorders paee anbody producon and e major se o desrucon o e Coagulation disorders result from either congenital or acquired IgG-coaed paees, so spenecomy s beneca. Cronc ITP s an deciencies of protein factors that are required for clotting. soaed dsorder a mus be dsngused rom secondar y ITP due Acqured decences are more common and are mos oten caused by : o oer condons (e.g., sysemc upus er yemaosus, drug exposure,    Vtamn K deicency. hs usuay occurs n e seng o HIV necon, and B-ce magnances). broad-specrum anboc erapy, nesna maabsorpon, or he onse o cronc ITP s nsdous. Common ndngs ncude mpared nuron, and resus n nadequae syness o pro- peecae, easy brusng, epsaxs, gum beedng, and emorrages ater rombn and cong acors VII, IX, and X and a severe coagua- mnor rauma. Serous nracerebra or subaracnod emorrages are on deec. Wararn s an ancoaguan drug a acs by nbng rare, bu occur. he dagnoss ress on e cnca eaures, e presence e syness o vamn K-dependen acors. o rombocyopena, and e response o erapy. Mos paens are    Lver dsease. he ver syneszes severa coaguaon acors and rs reaed w gucocorcods, wc nb macropage uncon aso removes many acvaed coaguaon acors rom e crcu- and rapdy correc e paee coun and somemes produce susaned aon; us, epac parencyma dseases are common causes o responses, even ater dsconnuance. For oers, spenecomy, an–B- compex coaguaon dsorders. ce erapes (e.g., an-CD20 anbodes), and rombopoen-ke    Dssemnated ntravascuar coaguaton (DIC; dscussed aer) oten drugs are oten efecve a conrong e rombocyopena. eads o decences o mupe acors.    Autoantbodes agans coaguaon acors cause acqured decen- Heparin-Induced Thrombocytopenia ces med o a snge acor. hs speca ype o drug-nduced rombocyopena mers a bre Heredar y decences o many coaguaon acors aso ave been menon because o s cnca mporance. Moderae o severe rom- dened. O ese, ony von Webrand dsease, emopa A, and bocyopena deveops n 3% o 5% o paens ater 1 o 2 weeks o emopa B are suceny common o warran urer consderaon. reamen w eparn. I s caused by IgG anbodes a bnd o Von Willebrand Disease paee acor 4 on paee membranes n a eparn-dependen as- on. Anbody bndng acvaes paees and nduces er aggregaon, Von Willebrand disease is a bleeding disorder caused by qualita- ereby exacerbang romboss, e condon a eparn s used o tive or quantitative defects in von Willebrand factor. rea. Bo venous and arera romboses occur, even n e seng o Von Webrand dsease s caracerzed by sponaneous beedng marked rombocyopena, and may cause severe morbdy (e.g., oss rom mucous membranes, excessve beedng ater dena procedures o mbs) and dea. Cessaon o eparn erapy breaks e cyce o or surger y, and menorraga I s more prevaen n persons o Euro- paee acvaon and consumpon. pean descen and s beeved o afec approxmaey 1% o peope n e Uned Saes, makng  e mos common nered beedng dsorder. Thrombotic Microangiopathies Von Webrand acor (vWF) s many syneszed n endoea he erm trombotc mcroangopates encompasses a specrum o cn- ces and megakar yocyes and exss n e pasma as arge mumers o ca syndromes a ncude romboc rombocyopenc purpura (TTP) up o 20 MDa n weg (Fg. 9.23). I aso s ound n e subendoe- and emoyc-uremc syndrome (HUS). her causes are dferen, bu a um, were  bnds o coagen. vWF as wo major uncons: are caracerzed by abnorma paee acvaon and deposon o pae-    vWF bnds to pateet gycoprotens, aowng vWF o ser ve as a e-rc romb n e mcrocrcuaon, eadng o rombocyopena moecuar “gue” beween subendoea coagen and paees o- and anema. In conras o DIC, acvaon o coaguaon acors s no a owng endoea damage (see Fg. 9.23). promnen eaure o HUS or TTP; consequeny, e PT and PTT are usu-    vWF bnds factor VIII, a coacor or acor IX, ncreasng s a- ay norma or ony sgy deranged. Because bo dsorders promneny e n e crcuaon and enancng dever y o acor VIII o ses nvove e kdney, ey are dscussed n Caper 11 o prmar y emosass. 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 Webrand dsease s us assocaed w deecs n bo as a “oregn” angen. hese dcu-o-rea paens may bene rom paee uncon and coaguaon; ony e paee deec produces erapy usng a bspecc anbody a cross-nks acor IX o acor X, cnca ndngs, excep n rare paens w omozygous von We- greay dmnsng e pysoogc requremen or acor VIII. brand dsease wo ave severe acor VIII decency. Hemophilia B–Factor IX Deficiency he cassc and mos common varan o von Webrand dsease s an auosoma domnan dsorder w reduced crcuang vWF and a Severe acor IX decency s an X-nked dsorder a s cncay measurabe bu cncay nsgncan decrease n acor VIII eves a ndsngusabe rom emopa A bu muc ess common. he proongs e PTT. Less common varees o von Webrand dsease ave dagnoss s made usng specc assays o acor IX. I s reaed by nu- muaons causng quaave deecs n vWF a ead o abnormay son o recombnan acor IX. arge or sma vWF mumers, prevenng norma prmary emosass. Disseminated Intravascular Coagulation he dagnoss s reaced by measurng e quany, sze, and uncon o vWF. vWF uncon s assessed usng e rstocetn pateet aggutnaton Disseminated intravascular coagulation is a condition in which test. Rsocen “acvaes” e bndng o vWF o paee gycoproens, cre- excessive activation of clotting results in the formation of thrombi ang nerpaee brdges a cause paees o cump (aggunaon), an in many tissues and secondary deciencies of platelets and coagu- easy quaned even a serves as a useu assay o vWF uncon. lation factors. Dssemnaed nravascuar coaguaon (DIC) occurs as a comp- Hemophilia A caon o a wde varey o dsorders. DIC can gve rse o eer ssue Hemophilia A, the most common hereditary cause of serious bleed- ypoxa and mcronarcs caused by mcroromb or o a beedng ing, is an X-linked disorder caused by deciency of factor VIII. dsorder reaed o depeon o e eemens requred or emosass Amos a afeced ndvduas are maes. Approxmaey 30% o (ence e erm consumptve coaguopaty). cases are caused by new muaons; n e remander, ere s a posve amy sor y. Severe emopa A s obser ved n peope w marked Pathogeness. Cong can be naed by eer e exrnsc paway, decences o acor VIII (acvy eves < 1% o norma). Mder de- wc s acvaed by ssue acor ; or e nrnsc paway, wc s cences may ony manes ater rauma or oer emosac sresses. acvaed wen acor XII neracs w coagen or oer negavey he var yng degrees o acor VIII decency are due o e exsence o carged subsances. Bo paways generae rombn, wc ceaves many dferen causave muaons. brnogen o orm a brn co. Cong s normay med o e se In sympomac cases, ere s a endency oward easy brusng and o njur y by a number o acors (see Caper 3). massve emorrage ater rauma or surgca procedures In addon, DIC may be rggered by (1) excessve reease o ssue acor or “sponaneous” emorrages requeny are encounered n ssues a are oer rombopasc subsances no e crcuaon or (2) wde- subjec o mecanca sress, parcuary jons, were recurren beeds spread endoea ce damage (Fg. 9.24). S evere endoea ce (emartroses) ead o progressve deormes a can be crppng. Beeds njur y exposes subendoea ssue acor and coagen. Even md no deep sot ssues (e.g., musces) and e bran aso may occur. endoea damage can uneas procoaguan acvy by smuang he dagnoss s suspeced based on a caracersc beedng sory ssue acor expresson we suppressng expresson o ancoagu- n an nan or young cd and e dencaon o a proonged PTT, an acors (e.g., rombomodun). Endoea njur y as a cenra and s conrmed w specc acor assays. Hemopa A s usuay roe n sysemc nlammaor y response syndrome (SIRS) rggered reaed w acor VIII nusons. In approxmaey 15% o ose w by sepss and oer sysemc nsus (see Caper 3); DIC s a re- severe emopa A, repacemen erapy s compcaed by e deveop- quen compcaon o SIRS. Dsorders assocaed w DIC are sed men o neurazng anbodes agans acor VIII, wc s recognzed n Tabe 9.10. O ese, DIC s mos oten assocaed w sepss, 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 bood, e speen s secondary nvoved by many sysemc dsorders. In vruay a nsances, e speen responds by enargng (speno- obserc compcaons, magnanc y, and major rauma (especay o megay), an aeraon a produces a se o sereoypca sgns and e bran). sympoms. Dsorders may be grouped accordng o e degree o spe- Once naed, DIC as wo consequences: (1) brn deposon n nomegay a ey caracerscay produce (Tabe 9.11). e crcuaon (romboss) and (2) depeon o paees and cong Wen enarged, e speen and s resden macropages oten remove acors w secondar y reease o pasmnogen acvaors, causng a excessve numbers o ormed bood eemens, resung n anema, euko- beedng dsorder a s paradoxcay supermposed on e excessve pena, or rombocyopena; s s reerred o as yperspensm. Paees cong. Pasmn ceaves no ony brn (brnoyss) bu aso acors are parcuary suscepbe o sequesraon n e nersces o e red V and VIII, ereby reducng er concenraon urer. In addon, pup; as a resu, trombocytopena s more prevaen and severe n per- brnoyss creaes brn degradaon producs a nb paee sons w spenomegay an s anema or neuropena. aggregaon, ave anrombn acvy, and mpar brn poymerza- on, a o wc conrbue o beedng. DISORDERS OF THE THYMUS Clncal Features. Dependng on e baance beween cong and beed- he ymus as a cruca roe n T-ce mauraon and s requeny ng endences, e range o cnca manesaons s enormous, rom mere nvoved by T-ce acue ympobasc eukema (T-ALL). he ocus aboraory abnormaes o muorgan aure, crcuaory coapse, and ere s on e wo mos requen (abe s uncommon) dsorders o massve, somemes aa, beedng. In genera, acue DIC (e.g., a assoc- e ymus, ymc yperpasa and ymoma, bo o wc may be aed w necon or obserc compcaons) s domnaed by beedng, assocaed w sysemc auommune dseases. wereas cronc DIC (e.g., as occurs n ose w cancer) more oten causes Thymic Follicular Hyperplasia romboss. Laboraory ess revea rombocyopena, proongaon o e PT and PTT, ncreased brn sp producs, and decreased brnogen. he he mos requen cause o ymc enargemen s ormaon o ympod presence o romb n sma vesses aso creaes sear sress a dsrups red oces and yperpasa o germna cener B ces, wc are no normay ces, producng so-caed mcroangopac emoyc anema. Red ce rag- presen n e ymus. hymc ocuar yperpasa s ound n mos mens caed scsocyes are caracerscay seen n e perpera bood. paens w myastena gravs (see Caper 18) and may occur n oer he prognoss s dcaed by e underyng dsorder and e sever- auommune dseases, suc as sysemc upus eryemaosus and reuma- y o e DIC. Acue DIC s e reaenng and s reaed aggressvey od arrs. Neer e cause o e ymc yperpasa nor s conrbu- w ancoaguans  romboss domnaes or by admnsraon o on o e assocaed auommune dsorders s undersood, bu remova o cong acors (res rozen pasma) and paees  beedng s e e yperpasc ymus may ead o remance o e myasena. prncpa probem. In conras, cronc DIC s somemes dened Thymoma unexpecedy by aboraor y esng. In eer crcumsance, e ony denve ner venon s reamen o e underyng cause. hymomas are neopasms derved rom ymc epea ces. hey may arse a any age, bu mos occur n mdde-aged adus. hey may be bengn or magnan. Mos ncude varabe numbers o nonneo- DISORDERS OF SPLEEN AND THYMUS pasc mmaure T ces. In abou 30% o cases, ymoma s assocaed w an auommune dsorder (e.g., myasena gravs, sysemc upus SPLENOMEGALY er yemaosus, pure red ce apasa). Remova o e ymoma may Prmar y dsorders o e speen are rare, bu as an mporan com- ead o remance o myasena gravs bu s ess efecve n reang ponen o e nnae and adapve mmune sysem and a er or e oer assocaed dsorders..  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 anaomcay desgned o repens oxygen and remove sudes. Pumonar y macropages resp ond o e njur y by pro ducng carbon doxde rom e bood. Gas excange depends on a nework pronammaor y medaors (Fg. 10.1) a acvae endoea ces. o capares a e cosey apposed o sac-ke ermna ar spaces Adeson moecues a bnd neurops are upreguaed, eadng caed aveo a are separaed rom e bood by a n ayer com- o sequesraon o e neurops n pumonar y capares. L o cay prsed o epea ces, a sma amoun o exraceuar marx, and pro duced c yoknes as o acvae e neurops, wc reeas e a a ayer o endoea ces. A broad range o dseases nvove e ung, varey o pro ducs (e.g., reacve oxygen sp eces, proeas es) a may ncudng nlammaor y, necous, and neopasc dsorders, many o ur er damage e aveoar epeum and endoeum. wc presen w sgns and sympoms reaed o abnormaes o gas excange. In s caper, we ocus on common dsorders a afec e Morphology. e soogc manesaon o acue respraor y ung and e upper ar ways. dsress syndrome s dfuse alveolar damage. In e acue pase, e ungs are dark red, irm, and eavy. Mcroscopc examnaon ACUTE RESPIRATORY DISTRESS SYNDROME reveas congeson, necross o aveoar epea ces, nersa and nraaveoar edema and emorrage, and (parcuary w Acute respiratory distress syndrome is a disorder in which damage sepss) coecons o neurops n capares. e aveo are oten to alveoli throughout the lungs causes edema and leads to respira- ned by yalne membranes conssng o ibrn-rc edema ud tory failure. mxed w debrs rom necroc epea ces (Fg. 10.2). In e Acue respraor y dsress syndrome afecs approxmaey 190,000 organzng stage, aveoar epeum proeraes o regenerae e paens per year n e Uned Saes and s aso reerred o cncay as aveoar nng. Heang may ead o resouon or o e deveopmen acue ung njury. I s caracerzed by e rapd onse o e-reaenng o ibroc ckenng o e aveoar was. respraor y nsucency, cyanoss, and severe arera ypoxema. Pathogeness. Acue respraor y dsress syndrome may o ccur n Clncal Features. Acue respraor y dsress syndrome usuay deve- asso caon w prmar y pumonar y ds eas es or sysemc nam- ops wn 72 ours o e na nsu. Mos paens requre nu- maor y dsorders. e mos  requen rggers are pneumona and baon and mecanca venaon, wc mproves oxygenaon, bu, sepss, oowed by aspraon, se vere rauma, pancreas, and rans- noneeess, approxmaey one rd o paens de, usuay because uson reacons. A o ese dsorders may caus e wdespread njur y o e underyng dsorder (e.g., sepss) or muorgan aure. Mos o aveoar endoea and epea ces, eadng o an accumua- paens wo sur vve recover norma respraor y uncon wn 6 on o edema ud n e aveoar nersum and e ar spaces o 12 mons, bu oers ave cronc respraor y nsucenc y rom and pro ducng a caracersc “weou” o e ungs on magng resdua aveoar ibross. 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 Cronc dseases a decrease pumonar y gas excange are dvded no (1) obstructve (arway) dsease, caracerzed by an ncrease n ressance o ar low caused by para or compee ar way obsruc- on a any eve, and (2) restrctve dsease, caracerzed by reduced expanson o e ung parencyma and decreased oa ung capacy. In obsrucve dseases, e orced va capacy (FVC) s norma or sgy decreased, wereas e expraor y low rae, usuay measured as e orced expraor y voume a 1 second (FEV ), s sgnicany 1 decreased. us, e rao o FEV o FVC s decreased. By conras, n resrcve dseases (dscussed aer), e FVC s reduced and e exp- raor y ow rae s norma or reduced proporonaey. Hence, e rao o FEV o FVC s near norma. e ree major obsrucve ung dsorders—empysema, cronc broncs, and asma—ave caracersc cnca and paoogc eaures n er prooypca orms (Tabe 10.1). Because empysema and cronc broncs oten coexs o var yng degrees, we w ds- cuss em ogeer under e rubrc o cronc obsrucve pumonar 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).