OS 210LEC 0X: TITLE

OS 213: Human Disease Treatment 3 (Circulation and Respiration)LEC 15: PNEUMONIAExam 2 | Dr. Regina Pascua-Berba| August 16, 2012

TransersUPCM 2016: XVI, WalangKapantay!3of 2

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Bobbie, Camille, GinnieUPCM 2016 B: XVI, Walang Kapantay!1 of 6

OUTLINEI. IntroductionII. PathophysiologyA. Route of InfectionB. Risk FactorsC. EtiologyD. Different Syndromes of PneumoniaIII. Clinical Presentation of PneumoniaA. Commone PresentationsB. Chest ExaminationsIV. Diagnostic Tools A. Chest X-rayB. Other Diagnostic TestsV. ManagementA. Decisions on Management B. Empiric TreatmentVI. PreventionVII. CasesVIII. Important Lecture PointsIX. Appendix

Objectives To understand the pathophysiology of pneumonia To differentiate the different syndromes, etiology, and presentations of pneumonia To discuss the recommended diagnostic and treatment management for CAP Suggested readings Harrisons Principles of Internal Medicine Philippine CPG for CAP in Immunocompetent Adults 2010 (PSMID- Philippine Society for Microbiology and Infectious Diseases has the guidelines) Infectious Diseases Society of America (IDSA) Guidelines for Community-acquired Pneumonia 2007

This trans is not complete because Dr. Berba has not sent us the slides yet! Boo! But dont you worry! Thisi s already meaty; well be serving the side dishes for higher learning (aka additional stuff on CAP and HAP, figures of radiologic pathologic findings, management accdg. to specific age group, and cheat sheet on Initial Empirical Antibiotic Therapy) through an appendix once we receive the slides. Anyways, for the exam, Dr. Berba said to focus on risk stratification (check out the Megatable and Summary).

I. INTRODUCTIONPneumonia Abnormal inflammatory condition of the lung Lower respiratory tract infection An infection of pulmonary parenchyma and alveolar compartment May be caused by various organisms Bacteria 70% Virus 10-20% Rarely parasites and fungi Usually patients are ill enough to require immediate attention Not a single disease; not self-limiting: patients are required to come in and be treated Group of specific infections based on: Epidemiology Pathogenesis Clinical Presentation and Course Identification of etiology is IMPORTANT! Diagnosis directs therapy; from empiric to specific anti-microbial regimen

Who are at Risk? Different people can get pneumonia at various points in their life (babies, elderly people, and even med students! :S) Those who are immunocompromised- leukemia, post-chemotherapy, etc

Burden of Illness Major cause of hospitalization worldwide Has significant health and economic consequences In the Philippines: 3rd leading cause of morbidity (2001) 3rd leading cause of mortality (1998) Worldwide, lung infection is the leading cause of DALYs lost (2002)

Fig. 1. Economic Consequences: Disability Adjusted Life Years

II. PATHOPHYSIOLOGYA. Route of Infection Microbes enter the lungs by:1. Hematogenous spread (Least common: ~2%) from an extrapulmonary site (distal to the lungs, ex. Carbuncle) Ex. Staphylococcus aureus in endocarditis2. Spread from a contiguous focus of infection (anything close to the lung parenchyma) Spread of infection from mediastinum Stab wound to the chest Necrotic cancer in chest wall or lungs3. Inhalation of aerosolized particles Common pathway Large particles more than 10 micrometer: dust, most bacteria Small airborne droplets less than 10 micrometer: TB, virus (like Influenza), Histoplasma, and Legionella Efficient: one particle can be lodged onto alveoli and initiate infection4. Aspiration of oropharyngeal secretions most common mechanism Healthy individuals may carry some organisms in their mouth, teeth, and gingival Increase w/ hospitalization, worsening disabilities, advanced age, alcoholism, and DM Aspiration during sleep, unconsciousness, seizure, NGT Impairment in fibronectin, cough reflex, mucociliary function Microbes travel down to lower respiratory tract (alveolar sacs and parenchyma) deposition of fibrinous material and pyrogenic cells, initiating inflammatory response interruption in gas exchange difficulty in breathing and increase in secretions Bacterial infection: neutrophils predominate Viral infection: lymphocytes predominate

Fig. 2. Alveoli in Pneumonia. Normally, alveoli are thin-walled. But here, there is thickened alveolar lining with fibrinous materials, heavyily laden with polymorphonuclear cells and purulent materials/exudates.

B. Risk Factors The normal airway and lungs are equipped with mechanisms to protect against infections. But there may be events that could lead to the impairment of these defense mechanisms. Risk Factors: Structural disease of orophraynx Impaired cough reflexes (i.e. alcoholics) Impaired mucociliary transport (i.e. smokers) Immunocompromised states Other Risk factors: Age > 65 yrs old Alcoholism- risk for aspiration, alcohol is generally bad for the immune system Smoking- destroys the cough reflex mechanism Asplenia- lacks antibodies Malnutrition COPD Previous episode of pneumonia Chronic bronchitis* Bronchiectasis* Cystic fibrosis* Diabetes Immotile cilia syndrome* Anatomic obstruction of bronchus* AIDS*Anatomic changes in respiratory system- will accumulate secretions and tend to be directed towards the evolution of pneumonia

C. Etiology Determining etiology is important in choosing empiric treatment

Table 1. Important Pathogens Causing PneumoniaYoung healthy adultStreptococcus pneumoniae, Mycoplasma pneumoniae, virus, TB

ElderlyS. pneumoniae, InfluenzaTB

DebilitatedS. pneumoniae, influenza, oral flora, TB, Gram-negative bacilli

HospitalizedOral flora, Staphylococcus aureus, Gram negative bacilli

ImmunocompromisedOral flora, Gram negative bacilli

*As patient becomes more and more immunocompromised, the prominence of Gram-negative bacteria as etiology increases

The severity of the disease (and therefore, the site of care, see Table 2) would be dictated by the specific organism that caused the pneumonia

Table 2. Microbial Causes of Community-Acquired Pneumonia, by site of care (Hospitalized Patients)OutpatientsNon-ICUICU

Streptococcus pneumoniaeMycoplasma pneumoniaeHaemophilus influzenaChlamydia pneumoniaeRespiratory Viruses

S. pneumoniaeM. pneumoniaeC. pneumoniaeH. influenzaLegionella spp.Respiratory VirusesS. pneumoniaeS. aureusLegionella spp. Gram(-) bacilliH. influenza

*consider the characteristics of your patient and the agent

D. Different Syndromes of Pneumonia

Community-acquired VS Hospital-acquired Involves different spectrum of etiologic agents Requires different empiric therapy; dictates initial management Community-acquired Pneumonia (CAP) Acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection accompanied by the presence of an acute infiltrate on a chest radiograph, or auscultatory findings consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for >14 days before onset of symptoms.

Examples: med student working in a hospital who gets pneumonia is still considered as CAP since he/she does not reside in the healthcare facility. patient admitted for cardiac problems (heart attack) in ICU Chest pain is because of inflammation that extends to pleura Lots of fibrinous secretions that go up PE: decreased breath sounds, increased vocal fremitus, dullness on percussion, crackles/rales (can help localize the area affected), increased whispered pectoriloquy, decrease movement on tactile fremitus Hospital-acquired Pneumonia aka Nosocomial pneumonia aka Healthcare-associated pneumonia caused by endemic flora of the hospital; usually Gram (-) bacteria but depends on the type of hospital 48 hours after admission (if before admission: community-acquired, if after: hospital-acquired); and not incubating at the time of admission VCAP-pneumonia which arises more than 48-72 hours after endotracheal incubation (V is for ventilatory?) HCAP-pneumonia within 90 days after receiving any form of health care

Chronic VS Acute Acute Pneumonia Chronic Pneumonia- if >2 weeks

Typical VS Atypical These are old terms Pneumonia might present in different/atypical ways

Table 3. Typical vs. Atypical Pneumonia (A very important table!)TypicalAtypical

Sudden onset of feverGradual onset of symptoms, often mild

Cough with purulent sputum- doesnt matter what colorDry cough

Shortness of breathShortness of breath

Pleuritic chest painExtrapulmonary symptoms: headache, mylagia, fatigue, sore throat, nausea, vomiting, diarrhea

PE with consolidation (dullness, increased fremitus, egophony, decreased bronchial breath sounds, rales)Systemic response of body not really understood until nowMinimal signs on PE

Usually caused by bacteria (Memorize!): S. pneumoniae H. influenza Moraxella catarrhalisUsually attributed to: Mycoplasma pneumoniae Chlamydophila pneumoniae Legionella spp.

III. CLINICAL PRESENTATION OF PNEUMONIAA. Common (Typical) Presentations of Pneumonia1. Cough: natural reflex to try to expel secretions2. Fever: part of the inflammatory response Caused by interleukins3. Chills: Kasabay po ba ng lagnat ay may panlalamig? Usually denotes bacterial or viral etiology4. Chest Pain: caused by pleuritic pain5. Difficulty in Breathing fluid-filled alveolar sacs inefficient for gas exchange Indicative of the severity of pneumonia Can be measured by respiratory rate6. Malaise

B. Chest Examination Early on in disease a fine crepitant rales over the involved portion of the lung(s) Progression to lobar consolidation results in: Dullness to percussion due to secretions and fluid in alveoli within the specific region in the lungs being percussed Vocal fremitus Whispered pectoriloquy Bronchial breathing

Table 4. Different Ways to Diagnose PneumoniaDecision BasisPhysicians Clinical JudgmentHeckerlings Score (threshold 2)Gennis Rule (threshold 1)

VariablesHistoryPETemp > 37.8Pulse >100RalesDecreased BSAbsence of asthmaTemp> 37.8RR> 20

Accuracy to Predict Pneumonia60-80%68%76%

IV. DIAGNOSTIC TOOLSA. Chest RadiographValue of Chest Radiograph For diagnostic certainty Assess severity of disease and prognostication Suggest possible etiology of pneumonia Help differentiate pneumonia from other conditions:

Correct CXR The following have to be considered to avoid misinterpretations Rotation- centered/ equidistant based on trachea; equal distance between medial end of clavicle and midline of the chest X-ray Penetration affected by technique of radiology; results might be mistaken for something else Inspiration/Expiration Remember your anatomy: (RUL, RML, RLL, LUL, LLL)

Fig. 3. Normal Chest Radiograph. Clear lung fields, normal shadow of pulmonary vascular markings and cardiac silhouette

Radiographic Findings Air Bronchogram- pathognomonic of pneumonia bronchial markings filled with gases, usually seen to penetrate dense infiltrates (as seen in CXR), or consolidation which indicates pneumonic process (as see in CT) in pneumonia w/o fluid, only inflammatory response = fremitus is increased, sounds are resonant, w/ crackles Meniscus Sign When no air bronchograms are seen, this suggests that lung is filled with fluid which forms a convexity Hilar mass lesion No obvious infiltrates, but presents with fever and cough Can already start treatment if clinically present with pneumonia Use CT scan to rule out malignancy Multiple masses Fungal pneumonia can present as multiple nodules work out if this is pneumonia or malignancy RUL collapse Clearly defined margin showing that the right lung is being pulled down Other observations: no air bronchograms, traction of midline structures Due to atelectasis, brought about by blockage of airway decreased lung sounds, decreased fremitus Cavitating lesion abscess/ TB cavity pneumonia can look initially as the usual infiltrates and then necrotize and form a cavity Millet seed - miliary TB (usually severe)miliary shadowing

Conditions Mimicking Pneumonia on X-ray Asthma or COPD Congestive heart failure (could present with crackles) Malignancy (primary lung or metastatic) Collagen vascular disorders (e.g. SLE, scleroderma) Pulmonary embolism Sarcoidosis Interstitial pneumonitis Pyelonephritis

B. Other Diagnostic Tests Sputum Gram strain and culture important! Sputum AFB (Acid Fast Bacilli) Induced sputum for PCP (Pneumocystis carinii) Serology for other atypical pathogens Mycoplasma pneumoniae Chlamydophilapneumoniae Legionella pneumophila

Sputum Examination Mainstay of evaluation of pneumonia Can identify etiology in only 50-60% of cases Good non-contaminated sputum Predominantly pus cells: PMN > 25/lpf (low power field) Proportionately less epithelial cells: Epithelial cells < 10/lpf With bacterial pathogens Observed in ~15 of cases studies Inadequate sample usually contain only saliva (with lots of epithelial cells > 25/lpf and no PMN) It is important fo us to INSTRUCT the patient on how to obtain appropriate sputum samples Hingang malalim 2 beses, umubo hanggang makapagbigay ng magandang halak Order gram stain and culture (Sputum GS/CS) More invasive tests as needed Important causative agent of community-acquired: Streptococcus pneumonia (if immunocompromised, Aspergillus and Candida)

Fig. 4.Streptococcus with many PMNs (polymorphonuclear cells)

Table 5. Clinical indications for more extensive diagnostic testingIndicationBlood CSSputum CSLegionella AntigenPneumococcal AntigenOthers

ICUXXXXX

Failure of OPD RxXXX

Cavitary InfiltratesXXX

LeukopeniaXX

Active Alcohol AbuseXXXX

Chronic severe liver diseaseXX

Severe Structural lung diseaseX

AspleniaXX

Recent travel (w/in 2 weeks)XX

Pleural EffusionXXXXX

V. MANAGEMENT Cant always rely on culture results to be readily available it takes 48 hours and unavailable in some areas NOTE: Decisions on Management and Empiric Management based on risk stratification were merged in one mega table! See last page

A. Decisions on Management According to risk stratification (check Megatable!), would have different mortality rates and site of care: CAP low risk CAP moderate risk CAP high risk HAP Other etiologies Etiologic agents vary for different age groups Scoring systems such as PORT and CURB-65 gave been developed for the recommendation of site of care; these are not usually used in the Philippines

Table 6. Pneumonia PORT Severity Index (PSI)Patient CharacteristicPoints Assigned

Demographic factors Age Male (no. yrs) Female (no. yrs. 10) Nursing home residentComorbid Illness Neoplastic disease Liver disease Congestive heart failure Cerebrovascular disease Renal diseasePhysical examination findings Altered mental status Respiratory rate 30 breath/min Systolic blood pressure < 90 mm Hg Temperature < 35 C Pulse > 125 beats/minLaboratory and/or radiographic findings Arterial pH < 7.35 Blood urea nitrogen 30mg/dL Sodium < 130 mmol/L Glucose > 250 mg/dLHeamtocrit< 30% Hypoxemia by O2 Saturation;< 90% by pulse oximetry,< 60 mm Hg by arterial blood gas Pleural effusion on baseline radiograph

--+10

+30+20+10+10+10

+20+20+20+15+10

+30+20+20+10+10

+10+10

Table 7. Pneumonia PORT Severity Index (PSI) InterpretationsTotal Point Score (points for each applicable patient characteristic)

PSI Risk ClassCharacteristic PointsRecommendedSite of Care

I

IIIII

IVVAge < 50 yrs + no comorbid conditions normal range vitalsigns, normal mental status 7071-90

91-130>130Outpatient

OutpatientOutpatient/Brief InpatientInpatientInpatient

Table 8.CURB 65 Severity Scores for CAPClinical FactorsPoints

Confusion1

BUN < 19 mg/dL1

Respiratory rate >/= 30 breaths/min1

Systolic BP < 90 mmHg or Diastolic BP > 60 mmHg1

Age > 65 years1

Total5

Table 9. CURB 65 Severity Scores for CAP InterpretationCURB Score Deaths (%)Recommendations

00.6Low risk; consider home treatment

12.7Low risk; consider home treatment

26.3Short inpatient hospitalization or closely supervised outpatient treatment

314.0Moderate risk; inpatient care

4 or 527.8Severe pneumonia; consider intensive care

Criteria for Severe Community-Acquired Pneumonia Minor Criteria (abnormal values for tests) Respiratory rate > or = 30 breaths per min PaO2/FiO2 < 250 Multilobar infiltrates Confusion, disorientation Uremia (BUN level > 20 mg/dl) Leukopenia (WBC count < 4,000 cells/mm) Thrombocytopenia (platelet count < 100,000 cells/mm2) Hypothermia (core temperature < 36 C) Hypotension requiring aggressive fluid resuscitation Major Criteria Invasive mechanical ventilation Septic shock with the need for vasopressin

B. Empirical Management According to risk stratification and likely etiology (check Megatable!)

Penicillin and/or drug resistant Streptococcus pneumoniae Age > 65 Beta-lactam therapy within the previous three months Alcoholism Immune suppressive illness (including use of corticosteroids) Multiple medical comorbidities Exposure to child in day care True for US but in the Philippines, penicillin is still effective (our S. pneumoniae is still sensitive to penicillin, yey!)

Enteric gram-negatives Moderate to severe types Residents in nursing homes Underlying cardiopulmonary disease Multiple medical comorbidities Recent antibiotic use

Pseudomonas aeruginosa One of the deadliest, signifies bad prognosis Difficult to treat (takes >2 weeks IV to completely eradicate)

Who are at risk for Pseudomonas? (EXAM QUESTION) History of prolonged antibiotic use (> 7 days) Broad-spectrum antibiotics (>7 days w/in last month) Chronic lung disease COPD, bronchiecstasis, cystic fibrosis Malnutrition Use of steroids Corticosteriod therapy (>10 mg Prednisone daily)

VI. PREVENTIONSmoking cessationPneumococcal vaccine For > 60 years old in the Philippines Once every five years Those with certain chronic illnesses Diabetes, Congestive Heart Failure, Chronic Liver Disease, COPD, Chronic Renal Disease, asplenia (reduction in antibodies) Those with immunocompromised states Residents of nursing homes and other long term facilities Smokers and asthmatic persons 19-64 years old The pneumonia shot protects against 23 serotypes of pneumococcus (there are 100 serotype) Not 100% effective in prevention but decreases chances of mortalityInfluenza vaccine For > 50 years Yearly, even if not viral pneumonia, since pneumonia can be superimposed on flu Those with chronic illnesses and immunocompromised states Pregnant in 2nd and 3rd trimester Residents of nursing homes Healthcare workers Household contacts and caregivers of persons w/ medical conditions and children 50 years Basically, EVERYONE4. Infection Control prevents transmission of pneumonia Hand hygiene/handwashing Isolation of sick patients Proper suctioning Wearing of masks more cost effective if patients will be the ones to wear masks Respiratory etiquette

VII. CASES

Case 1: y/o male, SM employee, non-smoker Chief complaint: cough and fever PE: crackles at Right base, decreased breath sounds 2 day history of high fever with chills and yellow phlegm Vital signs: 120/70, 39.8, RR 36, HR 110 Diagnosis: Low to Moderate risk CAP (right middle lobe) Management: Admit to ward, IV with penicillinase, 2nd generation cephalosporin/ cefuroxime

Case 2: 68/M Chief complaint: fever and cough Greenish phlegm, 30 pack-years Diagnosis: High Risk pneumonia (Strep, Varicella catarrhalis, pseudomonas) Expected PE: rales, crakles, whispered pectoriloquy, lag (tactile fremitus), consolidation (which would increase fremitus) or if liquid, decrease fremitus), diffuse wheezing (smoker) Management: admit to ward

Case 3: 40/M unresponsive, smells of mixed alcohol and vomitus Diagnosis: possible aspiration, high risk CAP (hemodynamic compromise), Pseudomonas Management: intubate/ ICU Intubate because multilobar, almost all lung fields

Case 4: 28/F pregnant 32 weeks AOG, required intubation Reticular patterns, diffused crackles, incessant coughs Viral (otherwise young) Diagnosis: high risk CAP Management: ICU, Pseudomonas antibiotics, AVOID using quinolones (teratogenic) Sputum G/S, nasopharyngeal swab This is a case where the patient missed her influenza shot before the pregnancy; bacterial pneumonia was superimposed on top of influenza

Case 5: 28/M Chief complaint: fever, shortness of breath Discharged 3 weeks for moderate CAP with Cefuroxime PE: clear lungs, tachycardic, chest XRay normal, CBC normal What tests to order (and their resuts)? Sputum (normal) ABG (slightly decreased) But Pneumocystis was identified Diagnosis: PCP Management: get ABG: hypoxemic (pO2: Normal= 80-100) In PCP, patients could be very ill yet with atypical manifestations.

VIII. IMPORTANT LECTURE POINTS Pneumonia is a frequently seen illness and all physicians must be familiar with its diagnosis and management Diagnosis by good history and PE, chest X-ray, and sputum test Risk stratification will guide management Prevention for those at risk Different etiologies depending on risk stratification so empiric therapy/drug of choice at presentation also varies

Table 10. Drug of choice for CAP typeClinical situationDrug of choice

Low risk CAPNo comorbiditiesAmoxicillin

Low risk CAPSuspecting atypical pathogensExtended macrolides

Low risk CAPStable comorbidities (ex. Controlled DM, asthmatic but with no attack in the last 10 years, etc)Amoxicillin clavulanic acidAmoxicillin sulbactamSultamicillinCefaclorCefuroxime+/- extended macrolide

Moderate risk CAPBeta-lactamCephalosporinErtapenem+ macrolide or respiratory quinolone

High risk CAPNo Pseudodomonas riskCeftriaxone or Ertapenem+ Macrolide or Respiratory quinolone

High risk CAPWith Pseudomonas riskPiperacillin-tazoCeftazidimeCarbapenem

END

Bobbie: Hello Millie and Ginnie! Hello to all Block B people! Im excited for sembreak! And Christmas!!!Camille: I love this week!Ginnie: Delikado magka long weekend. NAKAKATAMAD. Manood kayo ng Once Upon A Time! Hihi. Hello TritiPwidi! Maligayang Buwan ng Wika! Hi Millie and Bobbie! Hi Phil, just because. :P Hello sa mga kalaro kong guess the movie! Haha.

OS 213LEC 15: PNEUMONIA

TransersUPCM 2016: XVI, WalangKapantay!6of 6

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Megatable! Decisions on Management and Empiric Management of Pneumonia based on Risk StratificationLow Risk CAPModerate Risk CAPHigh Risk CAP

Vital Signs/Presentation Stable vital signs RR < 30 DBP > 60 SBP > 90 PR < 135 T < 40

Any one of the following: RR > 30 Pulse > 125 T < 35 or > 40 Chest X-ray with bilateral or multilobar involvement Pleural effusion Abscess Suspected aspiration CXR as in moderate risk CAP plus Unstable with any of: Impending or frank respiratory failure Hemodynamic alterations or hypoperfusion Altered mental state DBP < 60 mm Hg SBP < 90 mm Hg Urine output < 30 ml/hr

Mortality Low morbidity Mortality 5% Complicated Course Mortality 21% Mortality rate may be more than 36%

Site of Care Outpatient CareNeed to be hospitalizedICU admission

Etiology/Likely pathogensS pneumoniaH influenzaeC pneumoniaeM pneumoniaeM catarrhalisS pneumoniaH influenzaC pneumoniaM pneumoniaeM catarrhalisLegionella pneumophilaEnteric Gram-negative bacilliAnaerobesS pneumoniaH influenzaeC pneumoniaeM pneumoniaeM catarrhalisL pneumophilaS aureusPseudomonas aeruginosa

Empiric Therapy Use of Oral Antibiotics Depends on health status Previously healthy Amoxicillin or extended macrolide (Clarithromycin or Azitromycin) With stable comorbid illness Beta lactam/BLIC (beta lactamase inhibitor combination)(Coamoxyclav) OR 2nd gen cephalosporin +/- extended macrolides Use of IV antibiotics IV non pseudomonal Beta-lactam (BLIC, cephalosporin, carbapenem)PLUS (in the Phils) Extended Macrolide (to cover atypical pathogens)OR Anti-pneumococcal fluoroquinolone Depends on whether Pseudomonas is present or not No risk for Pseudomonas IV non pseudomonal Beta-lactam +/- B-inhibitorPLUS Macrolide OR quinolone Risk for Pseudomonas IV Pseudomonal coverage PLUS Macrolide +/- aminoglycoside or IV Ciprofloxacin

Others/Remarks May cause impaired gas exchange and multi-organ failure With ARDS/ Acute Respiratory Distress Syndrome (Fig 1.): lung failure because of overload needs mechanical ventilation

Figure 1. Relationship between Pneumonia and ARDS (Acute Respiratory Distress Syndrome) Captions:Normal Anatomy: Normal gas exchange across the alveolar walls allowing the uptake of fresh oxygen and the release of carbon dioxide. (Caption: Cut-section through Alveoli at Terminus of Bronchi)Pneumonia: Thickened and irritated alveolar walls with accumulation of mucus and inflammatory cellsPneumonia and ARDS: Upper box Thickened and irritated alveolar walls with accumulation of mucus and inflammatory cells; lower box Fluid releasing from capillaries filling this alveolar space and preventing gas exchange