PULMONARY PULMONARY INFECTIONSINFECTIONS

Prof.Dr.Ferda ÖZKANProf.Dr.Ferda ÖZKAN

Normal LungNormal Lung

The lungs are constructed to The lungs are constructed to carry out their cardinal carry out their cardinal function: the exchange of function: the exchange of gases between inspired air gases between inspired air and blood.and blood.

Normal LungNormal Lung The respiratory system is an outgrowth The respiratory system is an outgrowth

from the ventral wall of the foregut. from the ventral wall of the foregut. The midline trachea develops two lateral The midline trachea develops two lateral

outpocketings, the lung buds.outpocketings, the lung buds. The right lung bud eventually divides into The right lung bud eventually divides into

three branches-the main bronchi-and the three branches-the main bronchi-and the left into two main bronchi, thus giving rise left into two main bronchi, thus giving rise to three lobes on the right and two on the to three lobes on the right and two on the left.left.

The lingula on the left is the middle lobe The lingula on the left is the middle lobe equivalent; however, the left lung is equivalent; however, the left lung is smaller than the right. smaller than the right.

Normal LungNormal Lung The right main stem bronchus is The right main stem bronchus is

more vertical and more directly in more vertical and more directly in line with the trachea than is the left. line with the trachea than is the left. Consequently, aspirated foreign Consequently, aspirated foreign material, such as vomitus, blood, and material, such as vomitus, blood, and foreign bodies, tends to enter the foreign bodies, tends to enter the right lung rather than the left.right lung rather than the left.

Normal LungNormal Lung The main right and left bronchi The main right and left bronchi

branch give rise to progressively branch give rise to progressively smaller airways.smaller airways.

Progressive branching of the bronchi Progressive branching of the bronchi forms forms bronchiolesbronchioles, which are , which are distinguished from bronchi distinguished from bronchi by the by the lack of cartilage and submucosal lack of cartilage and submucosal glands within their walls. glands within their walls.

Normal LungNormal Lung Further branching of bronchioles Further branching of bronchioles

leads to the leads to the terminal bronchiolesterminal bronchioles,, which are less than 2 mm in which are less than 2 mm in diameter. The part of the lung distal diameter. The part of the lung distal to the terminal bronchiole is called to the terminal bronchiole is called the the acinusacinus; it is approximately ; it is approximately spherical, with a diameter of about 7 spherical, with a diameter of about 7 mm.mm.

Normal LungNormal Lung An acinus is composed of An acinus is composed of respiratory respiratory

bronchiolesbronchioles , which give off several alveoli from , which give off several alveoli from their sides. their sides.

These bronchioles then proceed into the These bronchioles then proceed into the alveolar alveolar ductsducts, which immediately branch into , which immediately branch into alveolar alveolar sacssacs, the blind ends of the respiratory passages, , the blind ends of the respiratory passages, whose walls are formed entirely of alveoli, which whose walls are formed entirely of alveoli, which are the site of gas exchange. are the site of gas exchange.

The alveoli open into the ducts through large The alveoli open into the ducts through large mouths. All alveoli are open and have incomplete mouths. All alveoli are open and have incomplete walls. A cluster of three to five terminal walls. A cluster of three to five terminal bronchioles, each with its appended acinus, is bronchioles, each with its appended acinus, is usually referred to as the pulmonary usually referred to as the pulmonary lobulelobule..

Normal LungNormal Lung The entire respiratory tree, including The entire respiratory tree, including

the larynx, trachea, and bronchioles, the larynx, trachea, and bronchioles, is lined by pseudostratified, tall, is lined by pseudostratified, tall, columnar, ciliated epithelial cells, columnar, ciliated epithelial cells, heavily admixed in the cartilaginous heavily admixed in the cartilaginous airways with mucus-secreting goblet airways with mucus-secreting goblet cells- except for the vocal cords, cells- except for the vocal cords, which are covered by stratified which are covered by stratified squamous epithelium, squamous epithelium,

The microscopic structure of the The microscopic structure of the alveolar wallsalveolar walls

The The capillary endotheliumcapillary endothelium lining the lining the intertwining network of anastomosing intertwining network of anastomosing capillaries. capillaries.

A A basement membranebasement membrane and surrounding and surrounding interstitial tissueinterstitial tissue separating the endothelial separating the endothelial cells from the alveolar lining epithelial cells. cells from the alveolar lining epithelial cells. In thin portions of the alveolar septum, the In thin portions of the alveolar septum, the basement membranes of epithelium and basement membranes of epithelium and endothelium are fused, whereas in thicker endothelium are fused, whereas in thicker portions, they are separated by an portions, they are separated by an interstitial space interstitial space ((pulmonary interstitiumpulmonary interstitium)) . .

Alveolar epitheliumAlveolar epithelium,, which contains a continuous which contains a continuous layer of two principal cell types: layer of two principal cell types:

- flattened, platelike flattened, platelike type I pneumocytestype I pneumocytes (or (or membranous pneumocytes) membranous pneumocytes)

- covering 95% of the alveolar surface and rounded covering 95% of the alveolar surface and rounded type II pneumocytestype II pneumocytes. .

Type II cells are important for at least two Type II cells are important for at least two reasons: (1) They are the source of reasons: (1) They are the source of pulmonary pulmonary surfactantsurfactant,, contained in osmiophilic contained in osmiophilic lamellarlamellar bodiesbodies seen with electron microscopy, and (2) seen with electron microscopy, and (2) they are the main cell type involved in the repair they are the main cell type involved in the repair of alveolar epithelium after destruction of type I of alveolar epithelium after destruction of type I cells. cells.

Alveolar macrophagesAlveolar macrophages, loosely attached to , loosely attached to the epithelial cells or lying free within the the epithelial cells or lying free within the alveolar spaces, derived from blood alveolar spaces, derived from blood monocytes and belonging to the monocytes and belonging to the mononuclear phagocyte system. Often, mononuclear phagocyte system. Often, they are filled with carbon particles and they are filled with carbon particles and other phagocytosed materialsother phagocytosed materials. .

The alveolar walls are not solid but are The alveolar walls are not solid but are perforated by numerous perforated by numerous pores of Kohnpores of Kohn, , which permit the passage of bacteria and which permit the passage of bacteria and exudate between adjacent alveoli exudate between adjacent alveoli

IntroductionIntroduction

Daily Daily 10,000 liters10,000 liters of air – filtered of air – filtered Nasopharyngeal flora (during Nasopharyngeal flora (during

sleep)sleep) Virulent organisms.Virulent organisms.

PneumoniaPneumonia: Inflammation of lung.: Inflammation of lung. Respiratory tract infections – Respiratory tract infections –

commonest in medical practice.commonest in medical practice. Enormous morbidity & mortality.Enormous morbidity & mortality.

EtiologyEtiology Decreased resistance - General/immuneDecreased resistance - General/immune Virulent infectionVirulent infection - - Lobar pneumoniaLobar pneumonia Defense MechanismsDefense Mechanisms

In the normal respiratory system there are a In the normal respiratory system there are a number of important number of important defense mechanismsdefense mechanisms that protect the lung from infection. These that protect the lung from infection. These include:include: Reflex Reflex closure of the vocal cords closure of the vocal cords Cough Cough reflex reflex Mucociliary Mucociliary clearance clearance MacrophageMacrophage activity and immune activity and immune

competencecompetence..

An An increased riskincreased risk of bacterial of bacterial infection is associated with infection is associated with impairment of the defense impairment of the defense mechanism, as in any of these mechanism, as in any of these clinical situations:clinical situations:

Loss of consciousnessLoss of consciousness ImmunodeficiencyImmunodeficiency state state Pulmonary Pulmonary edemaedema NeutropeniaNeutropenia Chronic airway Chronic airway obstructionobstruction Viral Viral infectioninfection..

ExudateExudateThe exudate in bacterial pneumonia is The exudate in bacterial pneumonia is typically composed of varying proportions typically composed of varying proportions of:of: edema fluid edema fluid red blood cells red blood cells leukocytes (principally neutrophils) leukocytes (principally neutrophils) fibrin fibrin

The cellular exudate in acute bacterial The cellular exudate in acute bacterial pneumonia is in the alveolar spaces and pneumonia is in the alveolar spaces and distal bronchioles though in severe cases distal bronchioles though in severe cases the major airways may also be filled with the major airways may also be filled with purulent secretion.purulent secretion.

TypesTypes

ViralViral BacterialBacterial MycoplasmalMycoplasmal FungalFungal

The Pneumonia SyndromesThe Pneumonia Syndromes Community-acquired Community-acquired

acute pneumoniaacute pneumonia Streptococcus Streptococcus

pneumoniapneumonia Haemophilus influenzaHaemophilus influenza Moraxella catarrhalisMoraxella catarrhalis Staphylococcus aureusStaphylococcus aureus Legionella Legionella

pneumophiliapneumophilia KlebsiellaKlebsiella PseudomonasPseudomonas

Community-acquired Community-acquired atypical pneumoniaatypical pneumonia MycoplasmaMycoplasma ChlamydiaChlamydia LegionellaLegionella Viruses (RSV, Viruses (RSV,

parainfluenza & parainfluenza & influenza, adenovirus)influenza, adenovirus)

Nosocomial pneumoniaNosocomial pneumonia Gram negative rodsGram negative rods Staphlyococcus aureusStaphlyococcus aureus

Aspiration pneumoniaAspiration pneumonia Anaerobic oral floraAnaerobic oral flora Amniotic fluidAmniotic fluid Gastric contentGastric content ChemicalsChemicals

Chronic pneumoniaChronic pneumonia NocardiaNocardia ActinomycesActinomyces Granulomatous Granulomatous

Necrotizing pneumoniaNecrotizing pneumonia AnaerobicAnaerobic Staphlyococcus aureusStaphlyococcus aureus KlebsiellaKlebsiella Streptococcus pyogensStreptococcus pyogens

Patterns of Pulmonary Patterns of Pulmonary infectionsinfections

AirwayAirway – – BronchitisBronchitis/Bronchiolitis/Bronchiolitis, , BronchiectasisBronchiectasis

ParenchymaParenchymaPneumonia Pneumonia

BronchopneumoniaBronchopneumoniaLobar pneumoniaLobar pneumonia

Lung abscessLung abscessTuberculosisTuberculosis

Several possible routes of infection Several possible routes of infection of the lung exist:of the lung exist: AspirationAspiration of contaminated secretions-- of contaminated secretions--

most common most common InhalationInhalation of infected airborne droplets of infected airborne droplets BacteremiaBacteremia    Direct extensionDirect extension of an acute of an acute

inflammatory process from an adjacent inflammatory process from an adjacent organ or structureorgan or structure..

Routes of InfectionRoutes of Infection

EtiopathogenesisEtiopathogenesis Causes of bacterial pneumonia can be categorized Causes of bacterial pneumonia can be categorized

as as extrinsicextrinsic and and intrinsic.intrinsic. Extrinsic factorsExtrinsic factors :: infection with respiratory infection with respiratory

pathogens. Exposure to pulmonary irritants or pathogens. Exposure to pulmonary irritants or direct pulmonary injury causes noninfectious direct pulmonary injury causes noninfectious pneumonitis.pneumonitis. Infectious agents responsible for bacterial Infectious agents responsible for bacterial

pneumonias include pneumonias include S. pneumoniaeS. pneumoniae and and H. H. influenzae;influenzae; Klebsiella, Staphylococcus,Klebsiella, Staphylococcus, and and LegionellaLegionella species; and gram-negative species; and gram-negative organisms.organisms.

Aspiration and inhalation of aerosols containing Aspiration and inhalation of aerosols containing the bacterial pathogen are the most common the bacterial pathogen are the most common modes of infection. modes of infection.

Some bacteria, such as Some bacteria, such as StaphylococcusStaphylococcus species, species, may spread to the lungs hematogenously.may spread to the lungs hematogenously.

S. pneumoniaeS. pneumoniae is the most common cause of is the most common cause of bacterial pneumonia.bacterial pneumonia.

Pneumonia from Pneumonia from H influenzaeH influenzae often is associated often is associated with debilitating conditions such as asthma, COPD, with debilitating conditions such as asthma, COPD, smoking, and a compromised immune system.smoking, and a compromised immune system.

K. pneumoniaeK. pneumoniae may cause a severe necrotizing may cause a severe necrotizing lobar pneumonia in patients with chronic alcoholism, lobar pneumonia in patients with chronic alcoholism, diabetes, or COPD.diabetes, or COPD.

S. aureusS. aureus pneumonia is observed in those who pneumonia is observed in those who abuse intravenous drugs. abuse intravenous drugs. S. aureusS. aureus generally occurs in hospitalized patients generally occurs in hospitalized patients

and patients with prosthetic devices; it spreads and patients with prosthetic devices; it spreads hematogenously to the lungs from contaminated hematogenously to the lungs from contaminated local sites. This pathogen also is an important local sites. This pathogen also is an important cause of pneumonia following infection with cause of pneumonia following infection with influenza A.influenza A.

L. pneumophilaL. pneumophila infections occur either sporadically infections occur either sporadically or as local outbreaks.or as local outbreaks.

Gram-negative pneumonias are Gram-negative pneumonias are observed in individuals who are observed in individuals who are immunocompromised or immunocompromised or hospitalized.hospitalized. Causative organisms include Causative organisms include

Escherichia coliEscherichia coli and and Pseudomonas, Pseudomonas, Enterobacter,Enterobacter, and and SerratiaSerratia species. species. Residents of chronic care facilities Residents of chronic care facilities are at risk for gram-negative are at risk for gram-negative pneumonia.pneumonia.

Intrinsic factorsIntrinsic factors :: related to the host's related to the host's immune response, the presence of immune response, the presence of comorbidities, and other risk factors:comorbidities, and other risk factors: Loss of protective reflexes allows Loss of protective reflexes allows

aspiration of oropharyngeal flora into the aspiration of oropharyngeal flora into the lung. lung.

Aspiration is facilitated by altered Aspiration is facilitated by altered mental status from intoxication, mental status from intoxication, deranged metabolic states, neurological deranged metabolic states, neurological causes (eg, stroke), and endotracheal causes (eg, stroke), and endotracheal intubation.intubation.

Local lung pathologies (eg, tumors, chronic Local lung pathologies (eg, tumors, chronic obstructive pulmonary disease [COPD], obstructive pulmonary disease [COPD], bronchiectasis). bronchiectasis).

Smoking impairs the host's defense to Smoking impairs the host's defense to infection by a variety of mechanisms.infection by a variety of mechanisms.

Aspiration pneumonia is observed in Aspiration pneumonia is observed in individuals with altered sensorium individuals with altered sensorium (eg, seizures, alcohol intoxication, (eg, seizures, alcohol intoxication, drug intoxication) or CNS impairment drug intoxication) or CNS impairment (eg, stroke). (eg, stroke). The stomach or oropharyngeal contents The stomach or oropharyngeal contents

are aspirated. are aspirated.

Complications of PneumoniaComplications of Pneumonia Destruction of lung tissue from infection Destruction of lung tissue from infection

(leading to bronchiectasis)(leading to bronchiectasis) Organization of the exudateOrganization of the exudate AbscessAbscess formation formation SpreadSpread of the infection to the pleural of the infection to the pleural

cavity (empyema) cavity (empyema) Sepsis & PyemiaSepsis & Pyemia Respiratory failureRespiratory failure Acute respiratory distress syndromeAcute respiratory distress syndrome Superinfection with gram-negative Superinfection with gram-negative

organismsorganisms DeathDeath

1. 1. PneumoniaPneumonia

1.1. 1.1. BronchopneumoniaBronchopneumonia

1.2. 1.2. Lobar pneumoniaLobar pneumonia

1.3. Viral 1.3. Viral (Atypical)(Atypical) pneumoniapneumonia

1.1. 1.1. BronchopneumoniaBronchopneumonia Staph, Strep, Pneumo & H. influenzaStaph, Strep, Pneumo & H. influenza Bronchopneumonia is characterized Bronchopneumonia is characterized

by focal areas of by focal areas of suppurative suppurative inflammationinflammation, in a patchy distribution, , in a patchy distribution, involving one or multiple lobes.involving one or multiple lobes.

Usually bilateralUsually bilateral Lower lobes commonLower lobes common Complications:Complications:

AbscessAbscess EmpyemaEmpyema DisseminationDissemination..

The inflammatory exudate in each of The inflammatory exudate in each of the foci of involvement the foci of involvement typically typically involves ainvolves a small airwaysmall airway and and surrounding alveolar spaces. surrounding alveolar spaces.

HistologicallyHistologically The The relatively small areas of relatively small areas of

involvementinvolvement Focal areas of Focal areas of suppurative inflammationsuppurative inflammation

in a patchy distributionin a patchy distribution.. Abscess formation.Abscess formation.

BronchopneumoBronchopneumoniania

Patchy consolidation – not limited to lobes

BronchopneumoBronchopneumoniania

BronchopneumoBronchopneumoniania

BronchopneumoniaBronchopneumonia:: Abscess Abscess formationformation

BronchopneumoniaBronchopneumonia

BronchopneumoniaBronchopneumonia

Bronchopneumonia - Abscess Bronchopneumonia - Abscess formationformation

Bronchopneumonia Bronchopneumonia - CT- CT

1.2. 1.2. Lobar PneumoniaLobar Pneumonia Fibrinosuppurative consolidation – whole Fibrinosuppurative consolidation – whole

lobelobe Rare Rare ((due to antibiotic treatmentdue to antibiotic treatment)) ~95% - Strep~95% - Strep.. pneumoniae types 1,3,7& pneumoniae types 1,3,7&

22 Four stagesFour stages (Laennec,1838) (Laennec,1838) : :

CongestionCongestion & edema (1 to 2 days) & edema (1 to 2 days) Red HepatizationRed Hepatization (2-4 days ) (2-4 days ) Gray HepatizaGray Hepatizatitionon (4 to 8 days) (4 to 8 days) ResolutionResolution (1 to 3 weeks) (1 to 3 weeks)..

CongestionCongestion & Edema & Edema::

This stage is characterized This stage is characterized histologically byhistologically by::

vascular engorgement, vascular engorgement, intra-alveolar fluid, intra-alveolar fluid, small numbers of neutrophils, small numbers of neutrophils, often numerous bacteria. often numerous bacteria. Grossly, the lung is heavy and Grossly, the lung is heavy and

hyperemichyperemic..

Red hepatizationRed hepatization:: Vascular congestion persists, Vascular congestion persists, Extravasation of red cells into Extravasation of red cells into

alveolar spaces,alveolar spaces, Increased numbers of neutrophils Increased numbers of neutrophils

and fibrin. and fibrin. The filling of airspaces by the The filling of airspaces by the

exudate leads to a gross appearance exudate leads to a gross appearance of solidification, or consolidation, of of solidification, or consolidation, of the alveolar parenchyma.the alveolar parenchyma.

A dry, granular, dark-red lung A dry, granular, dark-red lung surface on gross appearancesurface on gross appearance This appearance has been likened This appearance has been likened

to that of the liver, hence the term to that of the liver, hence the term "hepatization"hepatization".".

Gray hepatizationGray hepatization:: As pneumonia progresses over 2-3 As pneumonia progresses over 2-3

days, erythrocytes are lyseddays, erythrocytes are lysed with with persistence of the neutrophils and persistence of the neutrophils and fibrinfibrin and, epithelial cells and, epithelial cells degeneratedegenerate

The alveoli still appear The alveoli still appear consolidated, but grossly the color consolidated, but grossly the color is paler and the cut surface is drier.is paler and the cut surface is drier.

ResolutionResolution:: The exudate is digested by The exudate is digested by

enzymatic activity, and cleared by enzymatic activity, and cleared by macrophages or by cough macrophages or by cough mechanismmechanism..

Dying pneumococci release a Dying pneumococci release a preformed toxin, further contributing preformed toxin, further contributing to this damage. to this damage.

The pneumococci are opsonized by The pneumococci are opsonized by leukocytes and begin to be cleared. leukocytes and begin to be cleared.

Resolution results in the formation of Resolution results in the formation of jellylike yellowish-colored exudates. jellylike yellowish-colored exudates.

Absorption of these exudates is Absorption of these exudates is remarkably efficient, with little remarkably efficient, with little organization or permanent scaring.organization or permanent scaring.

Lobar Lobar PneumoniaPneumonia

Lobar Pneumonia – Lobar Pneumonia – Gray Gray hehepatizationpatization

StrepStrep.. Pneumoniae Pneumoniae PneumoniaPneumonia Streptococcus pneumoniaeStreptococcus pneumoniae produces produces

few toxins. few toxins. It causes diseases by its capacity to It causes diseases by its capacity to

replicate in host tissues. replicate in host tissues. The presence of a capsule allows an The presence of a capsule allows an

escape from phagocytosis, resulting in escape from phagocytosis, resulting in an intense inflammatory response in an intense inflammatory response in hosts who are immunologically naive. hosts who are immunologically naive.

Colonization of the oropharynx by Colonization of the oropharynx by bacterial adherence to human bacterial adherence to human pharyngeal cells is the usual first steppharyngeal cells is the usual first step. .

The alternative pathway of the The alternative pathway of the complement is first activated. complement is first activated.

Anticapsular antibodies are Anticapsular antibodies are effective in providing protection effective in providing protection against pneumococcal infection. against pneumococcal infection. They appear 5-8 days after the They appear 5-8 days after the

onset of infection. By this time, fever onset of infection. By this time, fever usually disappears in the absence of usually disappears in the absence of treatment. treatment.

Natural immunity follows Natural immunity follows infections as well as colonization. infections as well as colonization.

Conditions that predispose the patient to Conditions that predispose the patient to pneumococcal infectionpneumococcal infection Defective antibody formationDefective antibody formation

Agammaglobulinemia and Agammaglobulinemia and hypogammaglobulinemia, multiple myeloma, hypogammaglobulinemia, multiple myeloma, chronic lymphocytic leukemia, lymphoma, and HIV chronic lymphocytic leukemia, lymphoma, and HIV infectioninfection

Defective complement (C1 to C4)Defective complement (C1 to C4) Defective splenic functionDefective splenic function Asplenia and splenectomyAsplenia and splenectomy Chronic diseasesChronic diseases

Chronic obstructive pulmonary disease, cirrhosis Chronic obstructive pulmonary disease, cirrhosis of the liver, and alcoholismof the liver, and alcoholism

Acute viral respiratory infectionsAcute viral respiratory infections Post–influenza virusPost–influenza virus

Pneumonia: Pneumonia: The absence of predisposing factors is The absence of predisposing factors is

rare in pneumococcal pneumonia rare in pneumococcal pneumonia affecting elderly children, teenagers, affecting elderly children, teenagers, and adults younger than 60 years.and adults younger than 60 years.

Meningitis:Meningitis: Predisposing factors include head Predisposing factors include head

trauma, cerebrospinal fluid leak, and trauma, cerebrospinal fluid leak, and respiratory tract infection.respiratory tract infection.

ComplicationsComplications Pneumonia:Pneumonia:

Pleural effusionsPleural effusions AbscessAbscess Empyema.Empyema.

Meningitis Meningitis (if present)(if present) Cranial nerve palsies (III, VI, VII, VIII) usually Cranial nerve palsies (III, VI, VII, VIII) usually

disappear within a few weeks.disappear within a few weeks. Approximately 10% of infants and children are left Approximately 10% of infants and children are left

with persistent unilateral or bilateral sensory hearing with persistent unilateral or bilateral sensory hearing loss.loss.

Vasculitis and cerebral infarctionVasculitis and cerebral infarction epilepsy, and mental retardation.epilepsy, and mental retardation.

Obstructive hydrocephalusObstructive hydrocephalus Subdural empyema.Subdural empyema.

1.3. Atypical pneumonia1.3. Atypical pneumonia(Interstitial pneumonia)(Interstitial pneumonia)

Primary atypical pneumonia denotes Primary atypical pneumonia denotes the moderate amount of sputum, the moderate amount of sputum, no physical findings of consolidation,no physical findings of consolidation, moderate elevation of white cell moderate elevation of white cell

countcount lack of alveolar exudatelack of alveolar exudate

The etiologic agent in children:The etiologic agent in children: Virus (62%)Virus (62%) Bacteria (53%) Bacteria (53%) Both viral and bacterial pathogens-Both viral and bacterial pathogens-

mixed infection (30%).mixed infection (30%). The etiologic agent in adult: The etiologic agent in adult:

Bacteria (40%)Bacteria (40%) Virus (11%).Virus (11%).

1.3. Atypical pneumonia1.3. Atypical pneumonia(Interstitial pneumonia)(Interstitial pneumonia)

Mycoplasma infections are common Mycoplasma infections are common among children and young adults. among children and young adults. They occur sporadically or local They occur sporadically or local epidemics in closed communities.epidemics in closed communities.

Viral pneumonia can vary from a mild Viral pneumonia can vary from a mild illness to a life-threatening disease illness to a life-threatening disease with severe hypoxemia. with severe hypoxemia.

Adults frequently are infected with Adults frequently are infected with both bacterial and viral pathogens; both bacterial and viral pathogens; therefore, differentiating viral therefore, differentiating viral disease from bacterial disease may disease from bacterial disease may be impossible. be impossible. Patients with the greatest risk for Patients with the greatest risk for

severe disease:severe disease: Immunocompromised patients, Immunocompromised patients, Chronic illnesses. Chronic illnesses.

Nosocomial pneumonias:Nosocomial pneumonias: Adenovirus, Adenovirus, Influenza A and B, Influenza A and B, Parainfluenza, Parainfluenza, RSV. RSV.

Viruses are divided into categories Viruses are divided into categories depending on whether the pneumonia depending on whether the pneumonia they cause is a primary manifestation or they cause is a primary manifestation or part of a multisystem syndrome of part of a multisystem syndrome of disease. disease.

Pneumonia as a primary manifestation Pneumonia as a primary manifestation influenza virus types A and B, influenza virus types A and B, RSV, RSV, adenovirus, adenovirus, parainfluenza virus, parainfluenza virus, rhinovirus, rhinovirus, hantavirus, hantavirus, CMV. CMV.

Pneumonia as part of a multisystem Pneumonia as part of a multisystem syndrome syndrome ParamyxovirusParamyxovirus species (measles), species (measles), varicella-zoster virus, varicella-zoster virus, Epstein-Barr virus, Epstein-Barr virus, CMV, CMV, herpes simplex virusherpes simplex virus

PathologyPathology Bilateral/unilateral involvement,Bilateral/unilateral involvement, Patchy lesions,Patchy lesions, Inflammatory infiltration confined Inflammatory infiltration confined

within the walls, with:within the walls, with: EdemaEdema Mononuclear cells (lympho, histio, Mononuclear cells (lympho, histio,

plasma)plasma) In severe cases:In severe cases:

Diffuse alvolar damageDiffuse alvolar damage Hyaline membranes)Hyaline membranes)

Respiratory syncytial virus (RSV) Respiratory syncytial virus (RSV)

infectioninfection MManifests primarily as anifests primarily as

bronchiolitis and/or viral bronchiolitis and/or viral pneumoniapneumonia,,

Peak incidence of Peak incidence of occurrence is observed occurrence is observed at age 2-8 monthsat age 2-8 months..

Reinfection with RSV Reinfection with RSV occurs at all agesoccurs at all ages ((limited to the URTlimited to the URT).).

RSV bronchiolitis in the RSV bronchiolitis in the first year of life is one of first year of life is one of the most important risk the most important risk factors for the factors for the subsequent subsequent development of asthma.development of asthma.

RRisk for severe RSV isk for severe RSV infectioninfection:: less than six weeks of less than six weeks of

age,age, infants with a history of infants with a history of

prematurity, prematurity, those with congenital those with congenital

heart disease, chronic heart disease, chronic lung conditions or lung conditions or immunodeficiency. immunodeficiency.

Others: Others: lower socioeconomic lower socioeconomic

status, status, crowded living crowded living

conditions, conditions, exposure to passive exposure to passive

cigarette smoking cigarette smoking avoidance of breast avoidance of breast

feeding.feeding.

Respiratory viruses Respiratory viruses damage the respiratory tract damage the respiratory tract stimulate the host to release multiple stimulate the host to release multiple

humoral factors, humoral factors, histamine, leukotriene C4, and virus-specific histamine, leukotriene C4, and virus-specific

immunoglobulin E in RSV infection and immunoglobulin E in RSV infection and bradykinin, interleukin-1, interleukin-6, and bradykinin, interleukin-1, interleukin-6, and interleukin-8 in rhinovirus infections. interleukin-8 in rhinovirus infections.

RSV infections can also alter bacterial RSV infections can also alter bacterial colonization patterns, increase colonization patterns, increase bacterial adherence to respiratory bacterial adherence to respiratory epithelium, reduce mucociliary epithelium, reduce mucociliary clearance, and alter bacterial clearance, and alter bacterial phagocytosis by host cells.phagocytosis by host cells.

Lung RSV PneumoniaLung RSV Pneumonia

Influenza virusInfluenza virus The most common cause of viral pneumonia in adults. The most common cause of viral pneumonia in adults. Three serotypes of influenza virus exist: A, B, and C.Three serotypes of influenza virus exist: A, B, and C.

Influenza type AInfluenza type A is the serotype most frequently is the serotype most frequently responsible for major epidemics and pandemics; it responsible for major epidemics and pandemics; it is the most frequent cause of viral pneumonia in is the most frequent cause of viral pneumonia in adults.adults.

Influenza type A can alter surface antigens and Influenza type A can alter surface antigens and infect livestock; perhaps, this ability accounts for infect livestock; perhaps, this ability accounts for its ability to create a reservoir for infection and its ability to create a reservoir for infection and cause epidemics in humans. cause epidemics in humans.

Influenza type BInfluenza type B cause illness, which usually is cause illness, which usually is seen in relatively closed populations such as seen in relatively closed populations such as boarding schools. boarding schools.

Influenza type CInfluenza type C is less common and occurs as is less common and occurs as sporadic cases.sporadic cases.

Parainfluenza virusParainfluenza virus Parainfluenza infection occurs early in Parainfluenza infection occurs early in

life and may cause pneumonia.life and may cause pneumonia. Infection later in life is usually mild. Infection later in life is usually mild.

Four antigenically distinct serotypes of Four antigenically distinct serotypes of the virus exist; however, types 1, 2, and the virus exist; however, types 1, 2, and 3 cause more severe disease than that 3 cause more severe disease than that of type 4. of type 4.

Parainfluenza viruses are second in Parainfluenza viruses are second in importance to only RSV in causing lower importance to only RSV in causing lower respiratory tract disease in children and respiratory tract disease in children and pneumonia and bronchiolitis in infants pneumonia and bronchiolitis in infants younger than 6 months.younger than 6 months.

AdenovirusAdenovirus Type 7 viruses can cause bronchiolitis and Type 7 viruses can cause bronchiolitis and

pneumonia in infants. pneumonia in infants. Types 4 and 7 viruses are responsible for Types 4 and 7 viruses are responsible for

outbreaks of respiratory disease in military outbreaks of respiratory disease in military recruits. recruits.

Studies of atypical pneumonia in military Studies of atypical pneumonia in military personnel have shown that adenovirus is the personnel have shown that adenovirus is the etiology in as many as 40% of cases. etiology in as many as 40% of cases.

Severe adenovirus pneumonia may occur in Severe adenovirus pneumonia may occur in infants, immunocompromised patients, and infants, immunocompromised patients, and rarely, healthy adults.rarely, healthy adults.

ParamyxovirusParamyxovirus

Causing disease in unimmunized Causing disease in unimmunized children and adults. children and adults.

Immunity to measles (rubeola) is Immunity to measles (rubeola) is maintained throughout one's lifetime. maintained throughout one's lifetime.

Pneumonia occurs in 5% of measles Pneumonia occurs in 5% of measles cases, with death from measles in 1 cases, with death from measles in 1 per 1,000 patients. per 1,000 patients.

Most deaths are due to pneumonia.Most deaths are due to pneumonia.

CMVCMV An extremely important cause of pneumonia An extremely important cause of pneumonia

in immunocompromised patients. in immunocompromised patients. Reactivation of latent infection is almost universal Reactivation of latent infection is almost universal

in transplant recipients and individuals infected in transplant recipients and individuals infected with the human immunodeficiency virus. with the human immunodeficiency virus.

Additionally, CMV infection is immunosuppressive Additionally, CMV infection is immunosuppressive as well, causing further immunocompromise in as well, causing further immunocompromise in these patients. these patients.

The virus has been found in the cervix and in The virus has been found in the cervix and in human milk, semen, and blood products. human milk, semen, and blood products.

In cancer patients receiving allogenic bone In cancer patients receiving allogenic bone marrow transplants, CMV pneumonia has a marrow transplants, CMV pneumonia has a prevalence of 15% and a mortality rate of prevalence of 15% and a mortality rate of 85%.85%.

Varicella-zoster virus: Varicella-zoster virus: In immunocompromised children/adults.In immunocompromised children/adults.

Herpes simplex virus:Herpes simplex virus: Pneumonia may develop from primary Pneumonia may develop from primary

infection or reactivation.infection or reactivation. Epstein-Barr virus:Epstein-Barr virus:

Pneumonia as a complication of Pneumonia as a complication of mononucleosis is very uncommon. mononucleosis is very uncommon.

The virus can cause pneumonia in the The virus can cause pneumonia in the absence of mononucleosis.absence of mononucleosis.

Complications:Complications:

Respiratory failureRespiratory failure Pulmonary fibrosisPulmonary fibrosis Noncardiogenic pulmonary edemaNoncardiogenic pulmonary edema Superimposed bacterial infectionSuperimposed bacterial infection Adult respiratory distress syndromeAdult respiratory distress syndrome Reye syndromeReye syndrome

Severe Acute Respiratory Severe Acute Respiratory Syndrome SARSSyndrome SARS

First appeared in 2002 in ChinaFirst appeared in 2002 in China Coronavirus Coronavirus After incubation period of 2-10 days After incubation period of 2-10 days

patients develop dry cough, malasie, patients develop dry cough, malasie, myalgias, fever and chillsmyalgias, fever and chills

10% die of disease no specific treatment10% die of disease no specific treatment Can be detected by PCR or antibodiesCan be detected by PCR or antibodies The lungs of the patients show diffuse The lungs of the patients show diffuse

alveolar damage and multinucleated giant alveolar damage and multinucleated giant cellscells

Chronic PneumoniaChronic Pneumonia

Chronic pneumonia is most often a Chronic pneumonia is most often a localized lesion in the localized lesion in the immunocompetent patient, with or immunocompetent patient, with or without regional lymph node without regional lymph node involvement.involvement.

There is granulomatous infection, There is granulomatous infection, which may be due towhich may be due to

-bacteria -bacteria M. TuberculosisM. Tuberculosis --fungifungi H.capsulatum, Blastomycosis, H.capsulatum, Blastomycosis,

coccidioidescoccidioides

Fungal pneumoniaFungal pneumonia Endemic fungal pathogensEndemic fungal pathogens (eg, (eg, Histoplasma Histoplasma

capsulatumcapsulatum, , Coccidioides immitisCoccidioides immitis, , Blastomyces dermatitidisBlastomyces dermatitidis, , Paracoccidioides Paracoccidioides brasiliensisbrasiliensis) cause infection in both healthy ) cause infection in both healthy and immunocompromised host.and immunocompromised host.

Opportunistic fungal organismsOpportunistic fungal organisms (eg, (eg, CandidaCandida species, species, AspergillusAspergillus species, species, MucorMucor species, species, Cryptococcus neoformansCryptococcus neoformans) tend to cause ) tend to cause pneumonia in patients with congenital or pneumonia in patients with congenital or acquired defects in their host defenses.acquired defects in their host defenses.

Chronic PneumoniaChronic Pneumonia

EtiologyEtiology Workers or farmers with heavy exposure to bird, bat, or Workers or farmers with heavy exposure to bird, bat, or

rodent droppings and other animal excreta.rodent droppings and other animal excreta. C. immitisC. immitis, because of its virulence, also is a threat , because of its virulence, also is a threat

among laboratory personnel working with this fungus.among laboratory personnel working with this fungus. Conditions that predispose patients to any of the Conditions that predispose patients to any of the

opportunistic fungal pathogens are as follows:opportunistic fungal pathogens are as follows: Acute leukemia or lymphoma during myeloablative Acute leukemia or lymphoma during myeloablative

chemotherapychemotherapy Bone marrow transplantationBone marrow transplantation Solid organ transplantation on immunosuppressive Solid organ transplantation on immunosuppressive

treatmenttreatment Prolonged corticosteroid therapyProlonged corticosteroid therapy AIDSAIDS Prolonged neutropenia from various causesProlonged neutropenia from various causes Congenital immune deficiency syndromes.Congenital immune deficiency syndromes.

Histologic Findings:Histologic Findings: Caseating or necrotizing granulomas Caseating or necrotizing granulomas

with intracellular organisms inside with intracellular organisms inside macrophages (eg, macrophages (eg, H capsulatum, C H capsulatum, C immitisimmitis) )

Fungal hyphae in Fungal hyphae in AspergillusAspergillus and and MucorMucor species species

Intracellular yeast organisms in Intracellular yeast organisms in CandidaCandida species. species.

Complications:Complications: Blood vessel invasion (Dissemination and Blood vessel invasion (Dissemination and

sepsis)sepsis) Pulmonary hemoptysis, infarction, myocardial Pulmonary hemoptysis, infarction, myocardial

infarction, cerebral emboli, cerebral infarction, or infarction, cerebral emboli, cerebral infarction, or blindness.blindness.

Dissemimnation to other sites (brain, meninges, Dissemimnation to other sites (brain, meninges, skin, liver, spleen, kidneys, adrenals, heart, skin, liver, spleen, kidneys, adrenals, heart, eyes).eyes).

Other complicationsOther complications Bronchopleural or tracheoesophageal fistulasBronchopleural or tracheoesophageal fistulas Chronic pulmonary symptomsChronic pulmonary symptoms Mediastinal fibrosis (histoplasmosis)Mediastinal fibrosis (histoplasmosis) Broncholithiasis (histoplasmosis)Broncholithiasis (histoplasmosis) Pericarditis and other rheumatologic symptoms.Pericarditis and other rheumatologic symptoms.

TuberculosisTuberculosis

Pulmonary infection with Mycobacterium Pulmonary infection with Mycobacterium tuberculosis is tuberculosis is acquiredacquired as a result of as a result of inhalinginhaling the the tuberculosis bacillus suspended in the aerosolized tuberculosis bacillus suspended in the aerosolized sputum coughed up by an infected individual with sputum coughed up by an infected individual with "open" tuberculosis."open" tuberculosis.

Two phases of this disease occur:Two phases of this disease occur: PrimaryPrimary tuberculosis tuberculosis

By definition, this infection occurs in an By definition, this infection occurs in an individual not previously exposed and individual not previously exposed and sensitized to tubercle bacilli. sensitized to tubercle bacilli.

SecondarySecondary ( (reactivationreactivation) tuberculosis) tuberculosis By definition, this is tuberculosis which By definition, this is tuberculosis which

becomes clinically evident in an individual becomes clinically evident in an individual already sensitized to the tubercle bacillus. already sensitized to the tubercle bacillus.

The The sequence of eventssequence of events in primary infection in primary infection typically involves:typically involves: inhalation of infected airborne droplet inhalation of infected airborne droplet particle size (approximately 3 microns) favors particle size (approximately 3 microns) favors

deep inhalation and retention of the organism deep inhalation and retention of the organism the bacilli tend to locate in the subpleural the bacilli tend to locate in the subpleural

midzone of lung midzone of lung the earliest radiographic appearance is an ill-the earliest radiographic appearance is an ill-

defined localized "atypical" pneumonia defined localized "atypical" pneumonia after a brief acute inflammatory reaction after a brief acute inflammatory reaction

associated with a neutrophilic response, the associated with a neutrophilic response, the bacilli invoke granuloma formation. bacilli invoke granuloma formation.

By 2 to 8 weeks, the pneumonic focus By 2 to 8 weeks, the pneumonic focus becomes a more defined radiographic opaque becomes a more defined radiographic opaque single spheroidal lesionsingle spheroidal lesion Ghon focusGhon focus..

Primary TuberculosisPrimary Tuberculosis

In Non Immunized individuals In Non Immunized individuals (Children)(Children)

Primary Tuberculosis:Primary Tuberculosis: Self Limited diseaseSelf Limited disease Ghons complex or Primary complex.Ghons complex or Primary complex.

Primary Progressive TBPrimary Progressive TB 10% of adults, Immunosuppressed 10% of adults, Immunosuppressed

individualsindividuals Common in malnourished children Common in malnourished children Miliary TB and Meningitis.Miliary TB and Meningitis.

A single lesion (the A single lesion (the Ghon focusGhon focus)) occurs occurs just under the pleurajust under the pleura in the midportion ( in the midportion (in in the lower part of the upper lobesthe lower part of the upper lobes - --- the the best-ventilated area) of one lung. best-ventilated area) of one lung.

An active An active Ghon focusGhon focus is a 1-1.5 cm area of is a 1-1.5 cm area of gray-white inflammatory consolidation gray-white inflammatory consolidation circumscribed from the surrounding lung circumscribed from the surrounding lung tissue. tissue.

The bacilli The bacilli (either free or within (either free or within phagocytes) phagocytes) find their way to the regional find their way to the regional (tracheobronchial) (tracheobronchial) lymph nodes, and in a lymph nodes, and in a few weeks, granulomas have walled off few weeks, granulomas have walled off the bacilli in both locations.the bacilli in both locations.

The combination of lesions in the The combination of lesions in the lung lung and and lymph lymph nodenode involvement involvement is is called the called the Ghon complexGhon complex..

Healed complexes are small and may Healed complexes are small and may be hard to detect by either be hard to detect by either pathologic or radiologic studies.pathologic or radiologic studies.

Viable bacilli remain in the Ghon Viable bacilli remain in the Ghon focus/complex for life.focus/complex for life.

Entrance into the lymphatics permits Entrance into the lymphatics permits multiorgan dissemination.multiorgan dissemination.

The minimal lesion in the apex consists The minimal lesion in the apex consists of a 1-3 cm focal area of caseous of a 1-3 cm focal area of caseous consolidation consolidation remains remains localized/progress slowly localized/progress slowly rapid rapid caseationcaseation a fibrotic wall surrounds the a fibrotic wall surrounds the lesion.lesion.

MicroscopyMicroscopy::- Tubercule formation (by the epitheloid Tubercule formation (by the epitheloid

cells)cells)- Langhans’ giant cellsLanghans’ giant cells- Caseation (caseous necrosis)Caseation (caseous necrosis)- Lymphocytic infiltrationLymphocytic infiltration- Fibrosis.Fibrosis.

Course of the diseaseCourse of the disease The more The more usual courseusual course is the is the

fibrosis and calcification of the Ghon fibrosis and calcification of the Ghon complex; tubercle bacilli lie dormant complex; tubercle bacilli lie dormant even with fibrosis and calcification of even with fibrosis and calcification of the granulomas.the granulomas.

ThThee latent phaselatent phase may persist may persist throughout life, the only index of throughout life, the only index of infection being a positive PPD infection being a positive PPD (purified protein derivative) reaction (purified protein derivative) reaction and the presence of the obsolete and the presence of the obsolete fibrocalcific Ghon complex.fibrocalcific Ghon complex.

Subsequent course varies: Subsequent course varies: occasionallyoccasionally because of the virulence because of the virulence

of the organism or poor host resistance, of the organism or poor host resistance, infection spreads either via airspaces, infection spreads either via airspaces, leading to a leading to a tuberculous tuberculous bronchopneumoniabronchopneumonia,, or or

Via the bloodstream, leading to Via the bloodstream, leading to formation of myriads of small formation of myriads of small granulomas in one or several organs granulomas in one or several organs ((miliary tuberculosismiliary tuberculosis).).

Secondary/Reactive tuberculosisSecondary/Reactive tuberculosis Reactivation of dormant bacilli is Reactivation of dormant bacilli is

considered the most common source of considered the most common source of secondary tuberculosis, but secondary tuberculosis, but reinfectionreinfection from an outside source is believed to from an outside source is believed to occur in some cases. occur in some cases.

The The cause of reactivationcause of reactivation is presumed is presumed to be a decline in host to be a decline in host immunocompetence. immunocompetence.

There is increased risk for reactivation in There is increased risk for reactivation in patients with AIDS, alcoholism, diabetes, patients with AIDS, alcoholism, diabetes, certain malignancies, or undergoing certain malignancies, or undergoing steroid or radiation therapy.steroid or radiation therapy.

Secondary TuberculosisSecondary Tuberculosis

Post Primary in immunized Post Primary in immunized individualsindividuals

Reactivation or ReinfectionReactivation or Reinfection Apical lobes or upper part of Apical lobes or upper part of

lower lobeslower lobes Caseation, cavity - soft granulomaCaseation, cavity - soft granuloma Pulmonary or extra-pulmonary Pulmonary or extra-pulmonary Local or systemic/Local or systemic/mmiliaryiliary

Secondary TB arises in a previously Secondary TB arises in a previously sensitized individual, and sensitized individual, and ooccurs whenccurs when : : bacilli escape the original Ghon focusbacilli escape the original Ghon focus

(endogenous) or,(endogenous) or, more bacilli enter the body from outsidemore bacilli enter the body from outside

(exogenous)(exogenous). . The infection usually reappears The infection usually reappears inin the the apapical ical

or posterior segmentsor posterior segments of one or both of one or both upper upper lobelobess ( (Simon's focSimon's focii), and progress slowly.), and progress slowly.

Secondary tuberculosisSecondary tuberculosis active TB, active TB, postprimary tuberculosis, postprimary tuberculosis, adult tuberculosis, adult tuberculosis, reinfection tuberculosis, reinfection tuberculosis, cavitary tuberculosiscavitary tuberculosis

The location of granulomas is typically The location of granulomas is typically in the apices of the lungs. This is in the apices of the lungs. This is probably due to relatively high tissue probably due to relatively high tissue oxygen levels in this portion of the oxygen levels in this portion of the lung. The tubercle bacillus is lung. The tubercle bacillus is aerophilic.aerophilic.

The The fibrotic reactionfibrotic reaction tends to confine tends to confine the typical lesion, but concurrently the typical lesion, but concurrently there is an increased tendency to there is an increased tendency to tissue destruction and cavitation. tissue destruction and cavitation.

Cavitation favors proliferation of Cavitation favors proliferation of organism and spread to contacts.organism and spread to contacts.

Dissemination:Dissemination: Entrance into the lymphatics permits Entrance into the lymphatics permits

multiorgan dissemination. multiorgan dissemination. "Miliary" tuberculosis is characterized by "Miliary" tuberculosis is characterized by

numerous minute granulomas in lung and/or numerous minute granulomas in lung and/or extrapulmonary sites.extrapulmonary sites.

HypersensitivityHypersensitivity enhances resistance and enhances resistance and induces a more prompt response by activated induces a more prompt response by activated macrophages and fibroblasts.macrophages and fibroblasts. It is the variable spectrum of the interaction It is the variable spectrum of the interaction

of hypersensitivity and fibrotic reaction of hypersensitivity and fibrotic reaction which determines the natural course of the which determines the natural course of the disease, which ranges from cure through disease, which ranges from cure through continuous progression, or multiple continuous progression, or multiple exacerbations to death.exacerbations to death.

-tubercle formation (by the epitheloid cells)

-Langhans’ giant cells

-caseation

-lymphocytic infiltration

-fibrosis.

Other Types of Other Types of PneumoniaPneumonia

Congenital pneumoniaCongenital pneumonia Pneumonitis that presents within Pneumonitis that presents within the first 24 the first 24

hours after birth.hours after birth. Newborn infants typically have Newborn infants typically have sterile sterile

respiratory mucosa at birthrespiratory mucosa at birth, with subsequent , with subsequent uncontested colonization by microorganisms uncontested colonization by microorganisms from the mother or environment.from the mother or environment.

Accelerated access to distal respiratory Accelerated access to distal respiratory structures and bypass of much of the ciliary structures and bypass of much of the ciliary escalator occur in infants who require escalator occur in infants who require endotracheal intubation. endotracheal intubation. In these infants, increased physical disruption of In these infants, increased physical disruption of

epithelial and mucous barriers also occurs. In epithelial and mucous barriers also occurs. In addition, therapeutic exposure to high oxygen addition, therapeutic exposure to high oxygen concentrations and airway pressures interferes with concentrations and airway pressures interferes with ciliary function and mucosal integrity.ciliary function and mucosal integrity.

Pneumonia that becomes clinically Pneumonia that becomes clinically evident within 24 hours of birth may evident within 24 hours of birth may originate at 3 different times. originate at 3 different times. Overlap often exists among the 3 Overlap often exists among the 3 types, and assigning a particular types, and assigning a particular pneumonic episode to one of these pneumonic episode to one of these categories may be difficult. The 3 categories may be difficult. The 3 categories of congenital pneumonia categories of congenital pneumonia are are

(1) true congenital pneumonia, (1) true congenital pneumonia, (2) intrapartum pneumonia, (2) intrapartum pneumonia, (3) postnatal pneumonia(3) postnatal pneumonia. .

True congenital pneumonia is already True congenital pneumonia is already established at birth.established at birth.

Transmission of congenital pneumonia usually Transmission of congenital pneumonia usually occurs via 1 of 3 routes:occurs via 1 of 3 routes: 1. 1. Hematogenous transmission:Hematogenous transmission: If the mother has a If the mother has a

bloodstream infection, the microorganism can readily bloodstream infection, the microorganism can readily cross the few cell layers that separate the maternal cross the few cell layers that separate the maternal from the fetal circulation at the villous pools of the from the fetal circulation at the villous pools of the placenta.placenta.

22. . Ascending transmission:Ascending transmission: Ascending infection from the Ascending infection from the birth canal and aspiration of infected or inflamed birth canal and aspiration of infected or inflamed amniotic fluidamniotic fluid have significant common features. have significant common features.

33. . Transmission via aspirationTransmission via aspiration:: Most bacterial infections Most bacterial infections produce clinical signs of infection in the mother, but produce clinical signs of infection in the mother, but infections may not be evident if the membranes rupture infections may not be evident if the membranes rupture shortly after inoculation, similar to drainage of an shortly after inoculation, similar to drainage of an abscessabscess..

Intrapartum pneumonia is acquired during passage Intrapartum pneumonia is acquired during passage through the birth canal.through the birth canal. Intrapartum pneumonia may be acquired via Intrapartum pneumonia may be acquired via

hematogenous or ascending transmission, or it hematogenous or ascending transmission, or it may result from aspiration of infected or may result from aspiration of infected or contaminated maternal fluids or from mechanical contaminated maternal fluids or from mechanical or ischemic disruption of a mucosal surface that or ischemic disruption of a mucosal surface that has been freshly colonized with a maternal has been freshly colonized with a maternal organism of appropriate invasive potential and organism of appropriate invasive potential and virulence. virulence.

Infants who aspirate proinflammatory foreign Infants who aspirate proinflammatory foreign material, such as meconium or blood, may material, such as meconium or blood, may manifest pulmonary signs immediately after or manifest pulmonary signs immediately after or very shortly after birth.very shortly after birth.

Postnatal pneumonia in the first 24 hours of life Postnatal pneumonia in the first 24 hours of life originates after the infant has left the birth originates after the infant has left the birth canal.canal. Colonization of a mucoepithelial surface Colonization of a mucoepithelial surface

with an appropriate pathogen from a with an appropriate pathogen from a maternal or environmental source and maternal or environmental source and subsequent disruption allows the organism subsequent disruption allows the organism to enter the bloodstream, lymphatics, or to enter the bloodstream, lymphatics, or deep parenchymal structures. deep parenchymal structures.

Enteral feedings may result in aspiration Enteral feedings may result in aspiration events of significant inflammatory potential. events of significant inflammatory potential. Indwelling feeding tubes may further Indwelling feeding tubes may further

predispose infants to predispose infants to gastroesophageal reflux and other gastroesophageal reflux and other aspiration events. These infants are aspiration events. These infants are often relatively asymptomatic at often relatively asymptomatic at birth or manifest noninflammatory birth or manifest noninflammatory pulmonary disease consistent with pulmonary disease consistent with gestational age, but they develop gestational age, but they develop signs that progress well after 24 signs that progress well after 24 hours.hours.

Agents of chronic congenital infection Agents of chronic congenital infection may cause pneumonia in the first 24 may cause pneumonia in the first 24 hours of life; hours of life; Cytomegalovirus, Cytomegalovirus, Treponema pallidum, Treponema pallidum,

Toxoplasma gondii,Toxoplasma gondii, and others, and others, ChlamydiaChlamydia organisms presumably are organisms presumably are

transmitted at birth during passage transmitted at birth during passage through an infected birth canal, through an infected birth canal, although most infants are asymptomatic although most infants are asymptomatic during the first 24 hours and develop during the first 24 hours and develop pneumonia only after the first 2 weeks pneumonia only after the first 2 weeks of life.of life.

Pathology:Pathology: MacroscopyMacroscopy

The lung may have diffuse, multifocal, or The lung may have diffuse, multifocal, or very localized involvement with visibly very localized involvement with visibly increased density and decreased aeration. increased density and decreased aeration.

Frankly hemorrhagic areas and petechiae Frankly hemorrhagic areas and petechiae on pleural and intraparenchymal surfaces on pleural and intraparenchymal surfaces are common.are common.

Airway and intraparenchymal secretions Airway and intraparenchymal secretions may range from thin and watery to may range from thin and watery to serosanguinous to frankly purulent and serosanguinous to frankly purulent and frequently are accompanied by small-to-frequently are accompanied by small-to-moderate pleural effusions that display moderate pleural effusions that display variable concentrations of inflammatory variable concentrations of inflammatory cells, protein, and glucose.cells, protein, and glucose.

MicroscopyMicroscopy Mononuclear cells (macrophages, natural Mononuclear cells (macrophages, natural

killer cells, small lymphocytes) usually are killer cells, small lymphocytes) usually are noted early,noted early,

Granulocytes (eosinophils, neutrophils) Granulocytes (eosinophils, neutrophils) typically become more prominent later.typically become more prominent later. If systemic neutropenia is present, the number If systemic neutropenia is present, the number

of inflammatory cells may be reduced.of inflammatory cells may be reduced. Microorganisms.Microorganisms. Alveoli may be atelectatic from surfactant Alveoli may be atelectatic from surfactant

destruction or dysfunction, partially destruction or dysfunction, partially expanded with proteinaceous debris (often expanded with proteinaceous debris (often resembling hyaline membranes), or resembling hyaline membranes), or hyperexpanded secondary to partial airway hyperexpanded secondary to partial airway obstruction from inflammatory debris.obstruction from inflammatory debris.

Hemorrhage in the alveoli and in distal Hemorrhage in the alveoli and in distal airways is frequent. Vascular congestion airways is frequent. Vascular congestion is common; vasculitis and perivascular is common; vasculitis and perivascular hemorrhage are seen less frequently. hemorrhage are seen less frequently.

Inflammatory changes in interstitial Inflammatory changes in interstitial tissues are less common in newborns tissues are less common in newborns than in older individuals. than in older individuals.

Examination of the placenta may be Examination of the placenta may be useful. useful. An unusually large placenta with a thick An unusually large placenta with a thick

umbilical cord or necrotizing funisitis is umbilical cord or necrotizing funisitis is suggestive of congenital syphilis, with an suggestive of congenital syphilis, with an increased risk of congenital pneumonia alba. increased risk of congenital pneumonia alba.

Bronchiolitis ObliteransBronchiolitis Obliterans Organizing PneumoniaOrganizing Pneumonia

Characterized by the presence of Characterized by the presence of granulation tissue in the distal air spaces.granulation tissue in the distal air spaces.

When associated with granulation tissue When associated with granulation tissue in the bronchiolar lumen, organizing in the bronchiolar lumen, organizing pneumonia is qualified by the term pneumonia is qualified by the term bronchiolitis obliterans (BO). bronchiolitis obliterans (BO). Hence, the term bronchiolitis obliterans Hence, the term bronchiolitis obliterans

organizing pneumonia is used. organizing pneumonia is used.

Organizing pneumonia may be Organizing pneumonia may be classified according to whether classified according to whether (1) its cause is determined, (1) its cause is determined, (2) its cause is undetermined but (2) its cause is undetermined but

occurring in a specific and relevant occurring in a specific and relevant context, or context, or

(3) it is Cryptogenic (idiopathic) (3) it is Cryptogenic (idiopathic) organizing pneumonia (COP). organizing pneumonia (COP). Cryptogenic organizing pneumonia is a Cryptogenic organizing pneumonia is a

clinicopathologic syndrome characterized clinicopathologic syndrome characterized by rapid resolution with corticosteroids but by rapid resolution with corticosteroids but frequent relapses when treatment is frequent relapses when treatment is tapered or stopped. tapered or stopped.

Pathophysiology: Pathophysiology: Approximately one half of cases of Approximately one half of cases of

Bronchiolitis obliterans organizing pneumonia Bronchiolitis obliterans organizing pneumonia (BOOP) are idiopathic. (BOOP) are idiopathic.

A variety of conditions are associated with A variety of conditions are associated with BOOP as follows: BOOP as follows: Radiation therapy:Radiation therapy: In patients treated with In patients treated with

radiation therapy for small cell bronchogenic radiation therapy for small cell bronchogenic carcinoma or breast cancer, BOOP may affect the carcinoma or breast cancer, BOOP may affect the ipsilateral or contralateral lung. ipsilateral or contralateral lung.

Infections:Infections: Infection may be caused by Infection may be caused by Coxiella Coxiella burnetii, Pseudomonas aeruginosa,Mycoplasmaburnetii, Pseudomonas aeruginosa,Mycoplasma species, human herpesvirus 7 (after lung species, human herpesvirus 7 (after lung transplantation), transplantation), Pneumocystis cariniiPneumocystis carinii in patients in patients (after liver transplantation), influenza A virus, (after liver transplantation), influenza A virus, measles virus, parvovirus B19, HIV, measles virus, parvovirus B19, HIV, ChlamydiaChlamydia species, species, Plasmodium vivax,Plasmodium vivax, or or Plasmodium Plasmodium malariaemalariae. .

Drugs and toxins:Drugs and toxins: BOOP is associated BOOP is associated with exposure to minocycline; gold; with exposure to minocycline; gold; cephalosporin; acebutolol; sulfasalazine; cephalosporin; acebutolol; sulfasalazine; mesalazine; bucillamine; interferon mesalazine; bucillamine; interferon beta-1a; nitrofurantoin; amiodarone; beta-1a; nitrofurantoin; amiodarone; ticlopidine; carbamazepine; phenytoin; ticlopidine; carbamazepine; phenytoin; sotalol; rapid intravenous sotalol; rapid intravenous cyclophosphamide pulse therapy; a cyclophosphamide pulse therapy; a combination of cytosine arabinoside, combination of cytosine arabinoside, anthracyclines, and massive L-anthracyclines, and massive L-tryptophan ingestion, tryptophan ingestion, Sauropus Sauropus androgynusandrogynus vegetable poisoning, vegetable poisoning, exposure to paint aerosols in textile exposure to paint aerosols in textile workers, nylon flock workers, silo-filler's workers, nylon flock workers, silo-filler's disease, free-base cocaine use, and disease, free-base cocaine use, and smoke inhalation.smoke inhalation.

Associated pathologiesAssociated pathologies Connective tissue diseaseConnective tissue disease

Rheumatoid arthritis, Sjögren syndrome, ankylosing Rheumatoid arthritis, Sjögren syndrome, ankylosing spondylitis, polymyositis-dermatomyositis, cutaneous spondylitis, polymyositis-dermatomyositis, cutaneous vasculitis, Behçet disease, Wegener granulomatosis, vasculitis, Behçet disease, Wegener granulomatosis, ulcerative colitis, Crohn disease, systemic sclerosis, ulcerative colitis, Crohn disease, systemic sclerosis, systemic lupus erythematosus, systemic lupus systemic lupus erythematosus, systemic lupus erythematosus with antiphospholipid syndrome, primary erythematosus with antiphospholipid syndrome, primary biliary cirrhosis, and thyroiditis biliary cirrhosis, and thyroiditis

Immunosuppressed statesImmunosuppressed states Hematopoietic stem cell transplantation (HSCT), graft Hematopoietic stem cell transplantation (HSCT), graft

versus host disease of the liver after allogenic bone versus host disease of the liver after allogenic bone marrow transplantation, renal transplantation, coronary marrow transplantation, renal transplantation, coronary artery bypass graft surgery, kidney transplantation with artery bypass graft surgery, kidney transplantation with Fabry disease, T-cell leukemia, primary non-Hodgkin Fabry disease, T-cell leukemia, primary non-Hodgkin lymphoma, malignancies in children, myelodysplastic lymphoma, malignancies in children, myelodysplastic syndrome, recent surgery, severe pneumonia, adult syndrome, recent surgery, severe pneumonia, adult respiratory distress syndrome, and acquired immune respiratory distress syndrome, and acquired immune deficiency syndrome deficiency syndrome

Pneumonia in Pneumonia in Immunocompromised Immunocompromised

patientspatients

Pneumonia in the Pneumonia in the immunocompromised host involves immunocompromised host involves infection and inflammation of the infection and inflammation of the lower respiratory tract. lower respiratory tract.

It most commonly is seen in patients It most commonly is seen in patients infected with a human infected with a human

immunodeficiency virus (HIV), immunodeficiency virus (HIV), myelosuppressive chemotherapy, myelosuppressive chemotherapy, organ transplantation, organ transplantation, traditional immunosuppressive illness traditional immunosuppressive illness

Hodgkin disease.Hodgkin disease.

EtiologyEtiology P cariniiP carinii (in HIV-seropositive individuals) (in HIV-seropositive individuals) Gram-negative bacilliGram-negative bacilli StaphylococcusStaphylococcus and and AspergillusAspergillus species species

(predominant in patients with cancer)(predominant in patients with cancer) FungiFungi Viruses (particularly CMV)Viruses (particularly CMV) P. cariniiP. carinii initially with bone marrow initially with bone marrow

transplantation and transplantation and Streptococcus pneumoniaeStreptococcus pneumoniae more common latermore common later

Nosocomial bacteria initially in renal Nosocomial bacteria initially in renal transplantation, with opportunistic pathogens transplantation, with opportunistic pathogens more common later (eg, cytomegalovirus, more common later (eg, cytomegalovirus, P. P. carinii; Legionella, Aspergillus, Nocardiacarinii; Legionella, Aspergillus, Nocardia species)species)

Mycobacterium avium-intracellulare Mycobacterium avium-intracellulare (AIDS)(AIDS) Gram-negative bacilli initially with heart or liver Gram-negative bacilli initially with heart or liver

transplantation.transplantation.

Complications:Complications: PneumothoraxPneumothorax Hypoglycemia (may occur with Hypoglycemia (may occur with

pentamidine)pentamidine) Respiratory failureRespiratory failure Adult respiratory distress syndromeAdult respiratory distress syndrome SuperinfectionSuperinfection Pleural effusionPleural effusion EmpyemaEmpyema Death.Death.

...in ...in Immunocompromised Immunocompromised patientspatientsAspergillus and fungus Aspergillus and fungus

ballball

AspergillosisAspergillosis

Many substances can cause Many substances can cause chemical pneumonia, including chemical pneumonia, including liquids, gases, and small particles, liquids, gases, and small particles, such as dust or fumes, also called such as dust or fumes, also called particulate matter. Some particulate matter. Some chemicals only harm the lungs; chemicals only harm the lungs; however, some toxic materials however, some toxic materials affect other organs in addition to affect other organs in addition to the lungs and can result in the lungs and can result in serious organ damage or death. serious organ damage or death.

Chemical PneumoniesChemical Pneumonies

Chemical pneumonia includes: Chemical pneumonia includes: Insecticides Insecticides Pool cleaning chemicals Pool cleaning chemicals Gasoline fumesGasoline fumes Toxic gas (phosgene, chlorine)Toxic gas (phosgene, chlorine) Aspirated/Inhalated chemicals Aspirated/Inhalated chemicals

Complications of Chemical Complications of Chemical inhalation:inhalation: Cyanosis Cyanosis Pneumonia Pneumonia Respiratory failure.Respiratory failure.

Aspiration PneumoniaAspiration Pneumonia

Aspiration (the act of taking foreign Aspiration (the act of taking foreign material into the lungs), can cause a material into the lungs), can cause a number of syndromes determined by number of syndromes determined by the quantity and nature of the the quantity and nature of the aspirated material, the frequency of aspirated material, the frequency of aspiration, and the host factors that aspiration, and the host factors that predispose the patient to aspiration predispose the patient to aspiration and modify the response. and modify the response.

Three types of material cause 3 different Three types of material cause 3 different pneumonic syndromes. pneumonic syndromes. Aspiration of gastric acid causes chemical Aspiration of gastric acid causes chemical

pneumonia (Mendelson syndrome). pneumonia (Mendelson syndrome). Aspiration of bacteria from oral and pharyngeal Aspiration of bacteria from oral and pharyngeal

areas causes bacterial pneumonia. areas causes bacterial pneumonia. Inhalation/aspiration of chemicalsInhalation/aspiration of chemicals

Aspiration of oil, eg, mineral oil or vegetable oil, Aspiration of oil, eg, mineral oil or vegetable oil, causes exogenous lipoid pneumonia, a rare form of causes exogenous lipoid pneumonia, a rare form of pneumonia. pneumonia.

Organic dusts (hypersensitivity pneumonitis) Organic dusts (hypersensitivity pneumonitis) Inorganic particulates (silica, asbestos, talc, zinc) Inorganic particulates (silica, asbestos, talc, zinc) Chemical fumes (sulfuric acid, hydrochloric acid, Chemical fumes (sulfuric acid, hydrochloric acid,

methyl isocyanate) methyl isocyanate) Gases (oxygen, chlorine, nitrogen dioxide [silo-filler Gases (oxygen, chlorine, nitrogen dioxide [silo-filler

disease], ammonia, CO). disease], ammonia, CO).

Mendelson syndromeMendelson syndrome The parenchymal inflammatory The parenchymal inflammatory

reaction caused by a large volume reaction caused by a large volume of gastric contents independent of of gastric contents independent of infection. infection.

If the pH of the aspirated fluid is If the pH of the aspirated fluid is less than 2.5, it has a greater less than 2.5, it has a greater potential for causing chemical potential for causing chemical pneumonia. pneumonia.

The initial chemical burn is followed The initial chemical burn is followed by an inflammatory cellular by an inflammatory cellular reaction fueled by the release of reaction fueled by the release of potent cytokines (tumor necrosis potent cytokines (tumor necrosis factor–a and interleukin-8). factor–a and interleukin-8).

Bacterial pneumoniaBacterial pneumonia Nosocomial.Nosocomial. The major pathogens involved are hospital-The major pathogens involved are hospital-

acquired flora through oropharyngeal acquired flora through oropharyngeal colonization (eg, enteric gram-negative colonization (eg, enteric gram-negative bacteria, staphylococci). bacteria, staphylococci).

In anaerobic pneumonia, the pathogenesis is In anaerobic pneumonia, the pathogenesis is related to the large volume of aspirated related to the large volume of aspirated anaerobes (eg, as in persons with periodontal anaerobes (eg, as in persons with periodontal disease) and to host factors (eg, as in disease) and to host factors (eg, as in alcoholism) that suppress cough, mucociliary alcoholism) that suppress cough, mucociliary clearance, and phagocytic efficiency. clearance, and phagocytic efficiency.

Colonization of gram-negative organisms in Colonization of gram-negative organisms in the oropharynx, sedation, and intubation of the oropharynx, sedation, and intubation of the patient's airways are important the patient's airways are important pathogenetic factors inpathogenetic factors in nosocomial nosocomial pneumonia. pneumonia.

Risk factorsRisk factors Conditions associated Conditions associated

with altered or reduced with altered or reduced consciousnessconsciousness Alcoholism Alcoholism Drug overdose Drug overdose Seizures Seizures Stroke Stroke Head trauma Head trauma General anesthesiaGeneral anesthesia

Esophageal conditionsEsophageal conditions Dysphagia Dysphagia Esophageal strictures Esophageal strictures Esophageal neoplasm Esophageal neoplasm Esophageal diverticula Esophageal diverticula Tracheoesophageal fistula Tracheoesophageal fistula Gastroesophageal reflux Gastroesophageal reflux

diseasedisease

Neurologic disordersNeurologic disorders Multiple sclerosis Multiple sclerosis DementiaDementia Parkinson diseaseParkinson disease Myasthenia gravisMyasthenia gravis Pseudobulbar palsyPseudobulbar palsy

Mechanical conditionsMechanical conditions Nasogastric tubeNasogastric tube Endotracheal intubationEndotracheal intubation TracheostomyTracheostomy Upper gastrointestinal Upper gastrointestinal

endoscopyendoscopy BronchoscopyBronchoscopy

Other types of conditionsOther types of conditions Protracted vomitingProtracted vomiting General deconditioning and General deconditioning and

debilitydebility Prolonged recumbencyProlonged recumbency Amniotic materialAmniotic material

Eosinophilic pneumoniaEosinophilic pneumonia Characterized by pulmonary eosinophilia and Characterized by pulmonary eosinophilia and

infiltrates,infiltrates, with or without increased peripheral with or without increased peripheral

eosinophils in the blood. eosinophils in the blood. Causes: Causes:

Primary Eosinophilic pneumonias are idiopathic Primary Eosinophilic pneumonias are idiopathic and are not related to drugs, medications, or and are not related to drugs, medications, or systemic diseases such as vasculitis.systemic diseases such as vasculitis.

Secondary Eosinophilic pneumonias are Secondary Eosinophilic pneumonias are induced by induced by

Parasites (eg, Parasites (eg, Ascaris lumbricoides, Ascaris lumbricoides, Strongyloides stercoralisStrongyloides stercoralis), ),

Medications (eg, amiodarone, Medications (eg, amiodarone, nitrofurantoin).nitrofurantoin).

Histologic FindingsHistologic Findings Eosinophils with edema in alveolar Eosinophils with edema in alveolar

spaces and bronchioles are observed. spaces and bronchioles are observed. Additional cells are nonspecific and can Additional cells are nonspecific and can

include monocytes, histiocytes, and include monocytes, histiocytes, and polymorphonuclear leukocytes or polymorphonuclear leukocytes or neutrophils (PMN).neutrophils (PMN).

2. 2. Lung AbscessLung Abscess

Lung AbscessLung Abscess Focal suppuration with necrosis of lung Focal suppuration with necrosis of lung

tissuetissue Strep, Staph & Gram negative & Strep, Staph & Gram negative &

anaerobesanaerobes Mechanism:Mechanism:

AspirationAspiration of infected material of infected material Post pneumonicPost pneumonic Septic embolismSeptic embolism NeoplasmsNeoplasms Direct traumaDirect trauma SSpread from adjacent structurespread from adjacent structures..

Abscesses may occur in any location in Abscesses may occur in any location in the lung; they may be single or the lung; they may be single or multiple. multiple.

Abscesses due to aspiration occur most Abscesses due to aspiration occur most commonly in the right lung (because of commonly in the right lung (because of the more vertical course of the right the more vertical course of the right main stem bronchus) and are usually main stem bronchus) and are usually single.single.

Morphologically an abscess is a Morphologically an abscess is a cavity cavity filled with filled with suppurative debrissuppurative debris.. If communication exists with an airway, the If communication exists with an airway, the

exudate may drain, leading to air in the exudate may drain, leading to air in the cavity, and an air-fluid level on chest x-ray. cavity, and an air-fluid level on chest x-ray.

In chronic abscesses, there may be In chronic abscesses, there may be peripheral fibroblastic proliferation peripheral fibroblastic proliferation resulting in a fibrous wallresulting in a fibrous wall..

Complications:Complications: EmpyemaEmpyema Systemic spreadSystemic spread (pyemia/pyemic (pyemia/pyemic

abscesses)abscesses) SSepticemia.epticemia.

Lung AbscessLung Abscess

Lung AbscessLung Abscess

ChronicChronic Lung Abscess Lung Abscess

Fungal Abscess: Fungal Abscess: CandidaCandida albicans albicans

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