Pulmonary Pathology RESTRICT AND INFECTION 3.ppt

Two major lung diseasesTwo major lung diseases

1. Obstructive1. Obstructive – airway diseasea) limitations of airflow

i) partial or complete obstruction at any level major causes

a) asthma – obstructiveb) emphysema – loss of elastic recoilc) chronic bronchitisd) Bronchiectasise) cystic fibrosisf) bronchiolitis

1. Obstructive (con’t)1. Obstructive (con’t)

In these diseases:• TLC and FVC are normal or slightly increased• Marked by decreased expiratory flow (FEV1)• Ratio of FEV1 to FVC is decreased

2. Restrictive diseases2. Restrictive diseasesa) FVC is reducedb) ratio of FEV1 to FVC is increased or near normal

1.- Extrapulmonary disordersa) disorders which affect

chest to act as a bellows

b) examples: neuromuscal disordersi) Guillan-Barre Syndrome

2. Restrictive diseases2. Restrictive diseases (con’t)(con’t)

2.- acute or chronic interstitial lung disease

a) classic – ARDS (ie, shock lung, wet lung)

b) chronic disease – idiopathic pulmonary fibrosis,

pneumoconiosis, sarcoidosis

RESTRICTIVE LUNG DISEASERESTRICTIVE LUNG DISEASE

• reduced expansion (Decreased TLC)• reduced compliance !!

a) interstitial lung disease !!interstitial lung disease !!i) interstitial fluid or fibrosis cause lung

to be stiff which decrease lung compliance• Acute

a) edema (pulmonary; ARDS)b) inflammation

• Chronic (involvement of connective tissue)

a) fibrosis• Most diseases are idiopathic

• S & SS & Sa) dyspneab) tachycardiac) end expiratory “crackles”d) cyanosise) no “wheezing” or evidence of airway obstructionf) Cor pulmonale

• FeaturesFeaturesa) CO diffusing capacityb) TLCc) compliance

• Frequency of diseaseFrequency of diseasea) environmental diseases (~ 25%)b) sarcoidosis (~ 20%)c) IPF (~ 15%)d) collagen vascular disease (~ 10%)e) et al. (~ 30% - more than 100

causes) AlveolitisAlveolitis

a) earliest common S & S of interstitial disease

i) inflammatory and immune cells

- stimulate fibrosis via mediator release

- and initiates end-stage fibrotic lung disease

Chronic Restrictive Lung Disease Chronic Restrictive Lung Disease (interstitial lung disease)(interstitial lung disease)

• Some diseases also have alveolar component

• Decreased FVC (forced vital capacity)

• Decreased FEV1

• Ratio of FEV1/FVC is not reduced as was the case with obstructive pulmonary disease (increased or normal)

• ~15% of noninfections pulmonary disease

Idiopathic Pulmonary Fibrosis (IPF)Idiopathic Pulmonary Fibrosis (IPF) (usual interstitial pneumonia - UIP)(usual interstitial pneumonia - UIP)

a) diffuse interstitial fibrosisb) males more affected c) > 2/3 cases, patients older than 60

yearsd) recurrent cycles of lung injury

(alveolitis)i) current conceptii) wound healing fibroblast foci,

a characteristic finding of IPF- Tx might be directed to fibroblast replication

iii) with time, fibrosis causes a “honey- comb” fibrosis

- collapse of alveolar wall- formation of cystic spaces

filled with type II pneumocytes and bronchiolar epithelial

iv) secondary PHe) begins with some alveolar wall

injuryf) Hypothesized that immune

mechanisms are triggeri) IL-8 and leukotrienes recruit and

activate neutrophils!ii) injure alveolar epithelial cells

and degrade connective tissue

•Clinical courseClinical coursea) nonproductive coughb) progressive dyspneac) cor pulmonale, cyanosis and

peripheral edema may be present (later stages of disease); “clubbing”

d) abnormal chest x-raye) surgical lung biopsy is “Gold

Standard” for diagnosingf) treatment aimed at suppressing

inflammatory insulti) glucocorticoids

g) IPF so progressive 2 to 4 year survival after diagnosis; Tx lung transplant for

Non specific interstitial pneumonia Non specific interstitial pneumonia (NSIP)(NSIP)

• lung biopsy does not fit any other lung biopsy does not fit any other type oftype of interstitial diseaseinterstitial disease

a) “waste basket” type of diagnosisb) better outcome vs. IPF

• TypesTypesa) fibrosingb) cellular

i) better outcome than fibrosing

Cryptogenic organising Cryptogenic organising pneumonia(COP) or (BOOP; pneumonia(COP) or (BOOP; “bronchiolitis obliterans-organising “bronchiolitis obliterans-organising pneumonia”)pneumonia”)• Characterized by:Characterized by:

a) polypoid plugs of loose connective tissue w/in alveoli and bronchioles

b) no interstitial fibrosisc) no honeycomb lungd) some pts. recover spontaneously

i) most require steroids for > 6 months for recovery

e) COP w/intraalveolar fibrosis seen in response to:

i) infection, drugs, inhaled toxins

Collagen vascular diseaseCollagen vascular disease• Diseases:Diseases:

a) SLEb) RAc) sclerodermad) dermatomyositis – polymyositise) mixed connective tissue disease

PneumoconiosesPneumoconioses • ““Non neoplastic lung reaction to Non neoplastic lung reaction to inhalation of mineral dusts, organic, inhalation of mineral dusts, organic, inorganic particulates and chemical inorganic particulates and chemical fumes and vapors encountered in the fumes and vapors encountered in the workplace”workplace”

• Most dangerous particles range Most dangerous particles range from 1-5from 1-5 m diameter.m diameter.

a) reach terminal small airways and alveoli

i) settle in liningii) alveolar macrophages clear

small to moderate amounts• Solubility and cytotoxicity Solubility and cytotoxicity

a) smaller the particlesi) reach pulmonary fluids and

induce toxicity more quicklyii) small particles induce acute

lung injuryiii) large particles induce fibrosing

collagenous pneumoconiosis-Silicosis

b) particles stimulate fibroblasts scarring

i) may travel via lymphatics and induce systemic organ pathology

c) tobacco smokei) worsens affects of inhaled dust - e.g., asbestos toxicity

significantly magnified by tobacco smoke

• Only small % of people develop Only small % of people develop diseasedisease

a) many diseases listed in table are rare

b) a select few to induce pulmonary fibrosis at increased frequency

1.1. Coal workers pneumoconiosis Coal workers pneumoconiosis (CWP)(CWP)

• contaminating silica in coal dust contaminating silica in coal dust favorfavor

progression of disease (anthracosis)progression of disease (anthracosis)• carbon dust is primary culpritcarbon dust is primary culprit• VariationsVariations

a) asymptomaticb) simple CWP little or no

pulmonary dysfunctionc) complicated CWP progressing to “progressive massive fibrosis”

(PMF)• In absence of smoking In absence of smoking no no

evidenceevidence that CWP lead to cancer !!that CWP lead to cancer !!

2. 2. SilicosisSilicosis• inhalation of crystalline silicone inhalation of crystalline silicone dioxidedioxide (silica)(silica)• it is the most prevalent chronicit is the most prevalent chronic occupational disease in the world !!occupational disease in the world !!

a) presents as slowly progressing nodular fibrosing pneumoconiosis• Quartz most implicated in SilicosisQuartz most implicated in Silicosis• inhaled particles:inhaled particles:

a) activation and release of alveolar macrophage mediators

i) IL-1, TNF, fibronectin, ROS and fibrogenic cytokines

ii) TNF most implicated

• Quartz mixed with other minerals Quartz mixed with other minerals has has toxicity (i.e., toxicity (i.e., fibrogenic activity) fibrogenic activity)

• Silicosis first observed Silicosis first observed asymptomaticallyasymptomatically in upper zones of lungsin upper zones of lungs

• Silicosis Silicosis susceptibility to TB susceptibility to TB

• Crystalline silica from occupationalCrystalline silica from occupational sources is carcinogenic in humanssources is carcinogenic in humans

• Read file entitled “Silicosis” Read file entitled “Silicosis”

3. 3. Asbestos – related diseaseAsbestos – related disease• family of crystalline hydrated family of crystalline hydrated silicates silicates form fibersform fibers• occupational exposure causes:occupational exposure causes:

a) fibrous plaquesb) pleural effusionsc) lung CAd) mesotheliomae) laryngeal and colon CA ?

• 2 forms of asbestos2 forms of asbestosa) serpentine (i.e., curly and flexible)

i) most of asbestos used in industry

b) amphibole (i.e., straight, stiff and brittle)

i) more pathogenic - malignant mesothelioma

c) both forms are fibrogenicd) dose is associated with incidence

of all asbestos related diseasesi) except that only amphibole

exposure correlates with mesothelioma

• correlation of asbestos induced CA and smoking

Complications of therapyComplications of therapy• Drug – induced lung diseaseDrug – induced lung disease

a) acute (i.e., ARDS)b) chronic alterations in lung structure/function

i) bronchospasmii) edemaiii) DADiv) COPv) eosinophilic pneumoniavi) interstitial fibrosis

c) cancer chemotherapeutic drugsi) bleomycin

- direct toxic effects, fibrosis

• Radiation – induced lung diseaseRadiation – induced lung diseasea) radiation pneumonitis

i) Tx w/ steroids recoveryii) progression chronic

pneumonitisb) initial causes

i) lymphocytic alveolitisii) hypersensitivity pneumonitis

- pulmonary fibrosisc) DAD

i) hyperplasia of type II pneumocytes

ii) “ “ fibroblastsiii) presence of foam cells

SarcoidosisSarcoidosis

• Is a multisystem diseasea) unknown etiologyb) characterized by:

i) non caseating (i.e., “hard”) granulomas- other diseases such as

mycobacterial and fungal infrections, and berylliosis sometimes produce noncaseating granulomas, therefore diagnosis one of exclusion !!

ii) bilateral hilar lymphadenopathy present in > 90% cases !!

iii) next in frequency is eye and skin involvement (~ 25% of cases)

iv) one of few pulmonary diseases where incidence is higher

in non smokers !!v) 10x in American blacks vs.

whites, and in Southeast regionsvi) Danish and Swedish incidencevii) incidence in women vii) incidence in young adults <

40

Pathogenesis Pathogenesis • immune disorder is highly immune disorder is highly suggestivesuggestive

a) CD4+ helper T cellsi) intra alveolar and interstitial ii) T cell derived cytokines

- IL-2- IFN-

iii) IL-8, TNF and MIP-1- favors recruitment of T cells- contributes to formation of

granulomaiv) TNF at high levels in bronchoalveolar fluid

- marker for disease

• Environmental/genetic factorsEnvironmental/genetic factorsa) infectious agents no evidence of causal relationshipb) familial and racial clustering

i) HLA association (class I)- HLA - A1; HLA – B8

• ClinicalClinicala) ~ 70% recover with little affectb) ~ 20% have permanent loss of

some lung function or visual impairment

c) ~ 10-15% die of cardiac or CNS damage

i) most die of progressive pulmonary fibrosis and Cor Pulmonale

d) patients with hilar lymphadenopathy alone best prognosis; next is…

e) lymphadenopathy plus pulmonary infiltrates; poorest outcome is…c) pulmonary disease alone

i) most likely to develop pulmonary fibrosis (PPF)

• Granulomas preferentially involveGranulomas preferentially involve interstitium rather than air spacesinterstitium rather than air spaces a) localize around bronchioles and

pulmonary venules

• Erythema nodosum (raised tender red nodules on anterior aspects of legs)

a) hallmark skin lesion in acute sarcoidosis

• Another skin lesiona) lupus pernia

i) discoloration in region of nose, cheeks and lips

-

Hypersensitivity Pneumonitis (HP)Hypersensitivity Pneumonitis (HP)• Immune induced inflammatory lung disease

a) affects alveoli (allergic alveolitis)b) often is occupational disease

i) inhaled irritantsc) early diagnosis prevents PPF by

removal from antigen• Evidence for immune mediatedEvidence for immune mediated

a) MIP-1 and IL-8 in bronchoalveolar fluid

b) CD4+ and CD8+ T lymphocytes present

c) most patients have specific Antibodies (type III hypersensitivityimmune)

d) non caseating granuloma suggest delayed type IV hypersensitivity

• HP therefore is an immune HP therefore is an immune mediatedmediated disease innitiated by an extrinsic disease innitiated by an extrinsic antigenantigen that involves both type III and type that involves both type III and type IVIV hypersensitivity reactionshypersensitivity reactions

• Acute reactionAcute reactiona) feverb) coughc) dyspnea

• Chronic diseaseChronic diseasea) coughb) dyspneac) malaised) weight loss

• Most often inhaling dust containingMost often inhaling dust containing sporesspores

a) thermophilic bacteria/byproductsb) true fungi, animal proteinsc) names:

i) Farmers lung (humid, warm hay)ii) bird feeders lung (bird fanciers

disease)iii) air conditioning lung

• Unlike bronchial asthmaUnlike bronchial asthmaa) HP presents as restrictive lung

diseasei) Decreased diffusion capacityii) Decreased lung complianceiii) Decreased TLC

Pulmonary EosinophiliaPulmonary Eosinophilia

• Variety of disease, usually Variety of disease, usually immunologicimmunologic in originin origin

a) eosinophil attractant IL-5i) seen in alveoli in several

diseases• Groups:Groups:

a) acute eosinophilic pneumonia with respiratory diseaseb) simple pulmonary eosinophilia

(Löffler)c) tropical eosinophilia-microfilarial

infectiond) secondary (asthma, HP, drugs, etc)e) idiopathic chronic eosinophilic

pneumonia• Good response to glucocorticoid TxGood response to glucocorticoid Tx

Pulmonary alveolar proteinosis (PAP)Pulmonary alveolar proteinosis (PAP)

• Rare diseaseRare disease• presence of acellular surfactant inpresence of acellular surfactant in intraalveolar and bronchiolar intraalveolar and bronchiolar spacesspaces• Three classes:Three classes:

a) acquired PAPi) etiology unknownii) no familial predispositioniii) > 90% of all types of PAPiv) autoimmune disorder

b) Congenital PAPi) causes neonatal respiratory

distress syndromeii) fatal disorder w/out lung

transplant w/in 3-6 months

c) secondary PAPi) immune deficient disorderii) malignanciesiii) lysinuric protein intoleranceiv) acute silicosisv) other inhalation syndromes,

etc.

Pulmonary InfectionsPulmonary Infections• Pneumonia infections account for Pneumonia infections account for 1/6 of1/6 of all deaths in USA each yearall deaths in USA each year

a) epithelial surfaces of lung constantly exposed to contaminated air

b) nasopharyngeal flora normally aspirated during sleep

c) other lung parenchymal diseases render lung vulnerable to virulent organisms

• Pneumonia is a generic term Pneumonia is a generic term refers to refers to inflammation and consolidation (i.e. inflammation and consolidation (i.e. solidification)solidification)

a) Traditional bacterial pneumonia classified i) lobar - - consolidation of entire lobe

ii) bronchopneumonia - - scattered foci within same or several lobes

common cause of deathiii) today, these differences have

little clinical relevanceb) Bacterial pneumonias occur in 3

settingsi) community-acquired pneumoniaii) nosocomial pneumoniaiii) opportunistic pneumonia

c) broadly defined as any infection in the lungs

d) classification based on specific etiologic agent or clinical setting

e) evolution of lobar pneumococcal pneumonia

i) congestion – edema, exudate fluid

ii) red hepatization – alveoli packed with neutrophils, RBC, fibrin

iii) gray hepatization – dry, firm, color due to lysed RBC, exudate persist

iv) resolution – exudate enzymatically digested and resorbed

1.1. Community-acquired acute Community-acquired acute pneumoniapneumonia

a)a) bacterial in origin bacterial in origini)i) usually follows viral upper usually follows viral upper

respiratory respiratory infection infectionii)ii) Streptococcus pneumoniae (i.e., Streptococcus pneumoniae (i.e., pneumococcus) pneumococcus) most most

common common cause of cause of community-acquired community-acquired pneumoniapneumonia

b)b) patients present with abrupt: patients present with abrupt:i)i) high fever high feverii)ii) shaking chills shaking chillsiii)iii) productive cough productive cough

(mucopurulent)(mucopurulent)iv)iv) pleuritic chest pain pleuritic chest pain

c) These infections occur with increased frequency in patients

i) underlying chronic disease (CHF, COPD, diabetes)

ii) immunodeficiency (AIDS)iii) decreased splenic function

(organ responsible for removing strep pneumoniae from the blood) – seen

in sickle cell disease or post splenectomy !!

iv) aspiration of S. pneumonia with impaired epiglottic reflex

- alcohol intoxication- cold, anesthesia

d) Other organisms commonly implicated in community-acquired pneumonia

i) Hemophilus influenza- most common bacteria

cause of acute exacerbation of COPD

- is a pediatric emergency with high mortality rate

1. Causes meningitis2. Pinkeye in children

- ciliary movement- destroys IgA; main class of

antibody secreted into airways

ii) Staph aureus- high incidence of

complications (empyema and lung abscess)

- important in nosocomial infections- important cause of

secondary bacterial pneumonia following viral respiratory illness

1. Measels2. Influenza

- IV drug users at high risk

iii) Klebsiella pneumonia

- most frequent cause of gram (-) bacterial pneumonia

- commonly associated with alcoholism1. debilitated2. malnourished

- only other organism which causes lobar pneumonia

- accounts for only ~ 1 % of all CAP

iv) Legionella pneumophila- flourishes in artificial aquatic environments such as AC,

water towers, water tubing for drinking, water, etc.

- common in people with predisposing condition

(heart, renal, immunologic, blood)

- organ transplant patients risk

v) Moraxella catarrhalis (in elderly)

- 1 of the 3 (i.e., S. pneumoniae, H. influenza) most common causes of otitis media in children

e) S. pneumoniae normal inhabitant of nasopharynx - - false positive

culturesi) blood cultures more reliable

- resistant strains to penicillin - sensitivity test

OTHEROTHERa) Chlamydia psittaci

i) causes Psittacosisii) inhaled in dust contaminated

with excreta from birds, usually parrots !

iii) other pets as wellb) Pontiac fever (mainly febrile illness; Legionella sp.;

• COMPLICATIONS followingCOMPLICATIONS following pneumococcal pneumoniapneumococcal pneumonia

a) pleuritis (pneumonia extends to pleura)

b) pleural effusionc) empyema (pus in thorax)d) pyothorax (infection of pleural

effusion)e) bacteremia

i) > 25% of patients in early stage of pneumococcal pneumonia

- may lead to endocarditis or meningitis

- patients w/out spleen usually die !!!

f) pulmonary fibrosis (rare)

2.2. Community-acquired atypical Community-acquired atypical pneumonias (mycoplasma + pneumonias (mycoplasma +

viruses)viruses)a) most common organisms is mycoplasma pneumoniae

(others include viruses, chlamydiae and rickettsiae)

b) sputum production, WBC modest increase, bacteria and influenza A viruses not found

c) Chlamydia pneumonia increasing prevalence and important cause of this type pneumonia

d) Can produce some alveolar fluid accumulation, thus minimizing

bacterial pneumoniaee) secondary bacterial infectionsf) mycoplasma infections common in children and young adults

i) sporadic outbreaks in close communities (schools,

military camps, prisons)g) viral infections of lower respiratory

tract – influenza A and B i) most common in adults

h) adenovirus pneumoniaei) common in young army recruits

Atypical pneumoniaAtypical pneumonia (con’t) (con’t)i) More serious lower respiratory tract

infections in infancy, old age, malnourished, alcoholism

and immunosuppression j) Viruses and mycoplasmas frequently involved in outbreaks in hospitals (nosocomial)k) SARS “severe acute respiratory syndrome”

i) coronavirus pathogen- unlike other coronaviruses,

SARS infects lower resp. tract and spreads to rest of body

3. Nosocomial pneumoniaNosocomial pneumonia a) pseudomonas sp. Most common gram (-) rods (also Enterobacteriaceia)

i) gram(+) cocci – staph aureusb) Pulmonary infections acquired in the course of a hospital stayc) Common in patients with severe underlying disease,

immunosupression, antibiotic therapy, invasive devices such as catheters

i) mechanical ventilator increase incidence (“ventilator-

associated pneumonia”)d) strep. Pneumoniae NOT major strep. Pneumoniae NOT major

pathogenpathogen

4.4. Aspiration pneumoniaAspiration pneumoniaa) occur in severely debilitated

patients (unconscious e.g., following stroke), or during repeated vomiting

i) have abnormal gag and swallowing reflexes

b) pneumonia partly chemical (gastric or chemical irritant) plus bacterial

i) anerobes and aerobesc) necrotising frequent cause of deathd) patients who survive usually

develop abscess

• Lung Abcessa) Localized area of suppurative

necrosis within pulmonary parenchyma. Causative organism may be introduced into lung by many mechanisms

i) Aspiration of infected material- teeth (carious)- infected sinuses, tonsils- oral surgery

ii) aspiration of gastric contentsiii) septic embolismsiv) neoplasias (e.g., malignancies)

causing obstructions to the bronchopulmonary

segment.

b) Anaerobic bacteria are present in almost all lung abscesses

i) primarily those found on oral cavity

ii) most common aerobes are:- S. aureus- Nocardia- β – hemolytic strep.

5.5. Opportunistic pneumoniaeOpportunistic pneumoniaea)a) more common since advent of more common since advent of

immunosuppressive and cytotoxic immunosuppressive and cytotoxic therapy therapy b)b) AIDS epidemic AIDS epidemic

i)i) Pneomocyctic carinii (fungus) Pneomocyctic carinii (fungus)ii)ii) most common bacteria are most common bacteria are E. E.

colicoli and and Pseudomonas aeruginosaPseudomonas aeruginosa - - E.coli E.coli complication of complication of

bacteremia, cancer patients given bacteremia, cancer patients given chemotherapy, chronic heart and lung chemotherapy, chronic heart and lung disease. RESPONDS POORLY TO disease. RESPONDS POORLY TO TREATMENT !!TREATMENT !!

P. AeruginosaP. Aeruginosa (Con’t) (Con’t)

- P. aeruginosa often seen in burn patients, cystic fibrosis and immunocompromised pts.

- prior history of antibiotic treatment for another

infection is common- infectious vasculitis often

result in pulmonary infarction- ANTIBIOTIC TREATMENT IS USUALLY UNSSATISFACTORY

!!

TuberculosisTuberculosis• Communicable chronic Communicable chronic granulomatous granulomatous diseasedisease

a) Mycobacterium tuberculosisb) lungs are predominant target

but also involves other organsi) occurs in medically and economically deprived

populationsc) leading cause of death

worldwide !d) ~ 2 billion infected worldwide

i) 8-10 million new cases/yrii) 3 million deaths/yriii) 6% of all deaths worldwide

e) in 1984, in US there was increased incidence due to HIV-infected persons, Since 1992,

incidence of TB is decreasedf) In US, TB is disease of elderly (decreased immunity) and

immigrants• Higher incidence induced by other Higher incidence induced by other

diseasesdiseasesi) diabetesii) Hodgkin diseaseiii) chronic lung disease (e.g.,

silicosis)iv) malnutritionv) alcoholismvi) immunosuppression (i.e.,

HIV/AIDS)

• Most infections acquiredMost infections acquireda) direct person-to-person contactb) delayed hypersensitivity (PPD

[Purified Protein Derivative] test; mantoux test; tuberculin test)

i) false negative reactions- other viral infections- sarcoidosis - Hodgkin’s disease- malnutrition

ii) false positive reactions- atypical mycobacterium

c) contaminated milk (M. bovis) causing intestinal tuberculosis (rare in USA)

• Primary TBPrimary TBa) develops in previously unexposed (unsensitized) person

i) source of the organism is exogenous

ii) ~ 5% of newly infected people develop significant disease

b) chief implicationsi) induces hypersensitivity (type

iv)ii) increased resistance to

organismsiii) may be nidus for reactivation

when host defenses are decreased

iv) may develop without interruption

- Progressive primary TB (immunocompromised)

c) Eskimos more prone to develop progressive primary TB

d) Lymphohematogenous dissemination severe complication

i) tuberculosis meningitisii) miliary TB (organisms drain

through lymphatics and into central veins then to lungs – almost all organs are “seeded”) (liver, spleen, bone

marrow, meningitis)e) hallmark of TB is caseating

granulomas and cavitation (secondary)

i) implant in distal airways- lower part of upper lobe oror - upper part of lower lobe

ii) as sensitization develops- gray-white consolidation emerges “GHON FOCUS”“GHON FOCUS” (parenchymal lesion and

nodal involvement GHON COMPLEX)

iii) center of GHON focus undergoes caseous necrosis

iv) GHON COMPLEX undergoes progressive calcification

RANKE COMPLEX (detectable by x-ray)

• Secondary TB (post primary)Secondary TB (post primary)a) Pattern of disease that arises in previously sensitized host

i) may follow shortly after 1 TBii) more commonly arise from

dormant (reactivation) primary lesions many years (decades) after initial infection

b) Only few patients (~5%) with primary disease usually develop secondary TB

c) Classically localized to the apex of one or both upper lobes of the lungs

i) lymph nodes not as affected early vs. 1 TB

ii) cavitation does occur readily

- erodes along airway and becomes source of infection

pt. Raises sputum containing bacilli !

d) HIV patientsi) less severe immunosupression –

“usual” secondary TB (apical disease with cavitation)

ii) more severe immunosuppression – clinical picture resembling “progressive primary TB” (lower and

middle lobes, hilar lymphadenopathy, non

cavitating)

• Clinical (secondary)Clinical (secondary)

a) malaiseb) weight lossc) low grade fever

i) appearing late each afternoon then remitting

d) night sweatse) pleuritic painf) hemoptysis

• Nontuberculosis Mycobacterial Nontuberculosis Mycobacterial DiseaseDisease

a) Chronic pulmonary disease in immunocompetent people is most common localized disease

caused by nontuberculosis mycobacteria

• Fungal InfectionsFungal Infectionsa) Molds and yeast

b) Histoplasma c) Aspergillus d) Candida – most frequent disease causing fungus e) Cryptococcus