Pulmonary Infections Upper respiratory tract infections (colds) lower repiratory tract infections (bronchitis and pneumonia) Pneumonias,

s, highly associated with mobidity and mortality, major cause of death in US o Patients with other disease develop terminal pneumonia -> hospital environment Pneumonia(s) Pneumonaie Description Morphology Infection of lung parenchyma -sometimes describes noninfectious -chemical injury -> aspiration Etiologies Agents reach lungs: - inhalation - direct extension from infectious foci - hemtogenous spread - invade respiratory tract Clinical Course/ Complications Immunocompromised patients -> impaired general immunity of pulmonary immunity compromised

Community Acquired Pneumonia

Bacterial pneumonia Strep. Pneumoniae

Common organsism: - Strep. Pneumonia (30%) - Hemophilius influenzae (10%) - Mycoplasma pneumoniae (10%) - Chlamydia pneomoniae (8%) - influenza (7%) - Legionella sp. (3%) - G Enterobacteriaceae (3%) - Chlamydia psittaci (1%) - 40% of cases no defined pathogen Inflammatory exudate -> tissue consolidation Common cause of commmunity acquired 5-25% of healthy person -> carriers Colonizes the pharynx in encapsulated (5%) and nonencapsulated (95%) Type b encapsulated most frequent form mortality rate before vaccination -> was most common cause of supprative menegitis Most frequent G- bacteria pneumonia Nosocomial infections Frequent cause of nosocomial pneumonia Lobar pneumoniae with consolidation of entire lobe inflammation of trachea and bronchi -> dense firin rish exudate -> airway obstruction Pathcy or confluent areas of consolidation

Follow viral URI Bacterial invasion of lung parenchyma < 2 y/o or >/= 65 y/o risk chronic heart, lung, or liver disease or sickle cell anemia Capsule prevents opsonization by leukocytes -> impaired phagocytosis vaccination is causing number of non-encapsulated cases to Common bacterial cause of acute exacerbation of COPD Prevalent in chronic alcoholics Frequent causative agent in patients with CF Frequent causative agent in patients with CF Causes secondary

Identified by gram stain of sputum or culture -vaccines available for risk Important cause of supprative menegitis Type b encapsulated prevented by vaccine Can cause conjunctivitis, endocarditis, pyelonerphritis, cholecystis, arthritis

H. influenzae

Klebsiella pneumoniae Pseudomonas aeruginosa Staph. Aureus

Viscoid capsular polysaccharide with thick gelatinous sputum Patchy bronchopneumoniae and lobar pneumoniae

High rate of complications - Lung abscesses

pneumoniae in patients with influenza and other resp. illnesses Moraxella catarrhalis Legionella pneumophila Grows well in aquatic enviroments Common cause of bacterial pneumoniae in elederly 2nd most common cause of acute exacerbation of COPD Mode of transmission through aerosol droplets -> aspiration Organ transplant receipents vunerable, also patients with chonic heart or kidney disease

empyema

Pneumonia complications -> abscesses -> localized collection of pus organization of the exudate -> areas of pulmonary fibrosis Hematogenous spread to other sites -> causing infectious lesions in those sites -> endocardium, pericardium, brain, meneiges, kidneys, joints, spleen Clinical Course Classic symptoms -> fever, chills, productive cough +/- hemoptysis, +/pleurtic pain and friction rub, pleurtic pain - WBC shows neutrophilic leukocytes w/ left shit ( presence of band forms) Course modified by therapy -> identification of organisms by culture and appropriate therapy <10% of hospitalized patients die due to predisposing conditions or complications such as supprative menegitis

Bronchopneumoniae Lobar Pneumonia

Most common form of bacterial pneumoniae

Patchy foci of supprative inflammation, grossly Neutrophilic fills bronchi, bronchioles, and spreads to adjacent alveolar spaces Heals by partial resolution + scarring Resolution -> enzymatic disestion of exudate -> semi fluid debris is Adult males reabsorbed, ingested by macrophages, coughed up rarely, organized by Four classic stages -> therapy has ingrown fibroblasts (after day 8) changed the course of disease Inflammation -> extend to pleura -> fibrous pleuritis eventually resolve progression or heal -> fibrous adhesions b/w pleural layers congestion -> vascular congestion, intra-aveolar fluid with minimal inflammatory cells -> often many bacteria (1-2 days) Red hepatization -> erythrocytes, neutrophils, fibrin fill alveolar spaces ->

gross liver like consistency (2-4 days) Gray hepatization -> red cells have disintegrated but white cells and fibrin persist -> gray appearance grossly (4-8 days)

Atypical pneumoniae walking pneumonia

Atypical -> pneumoniae with less dramatic findings when compared with usual bacteria pneumoniae - mild to moderate sputum comparison - lack of signs of consolidation - modest elevation of WBC count - No alveolar exudate

Interstial inflammation with infiltration of alveolar septae by lymphocytes, macrophages, plasma cells; neutrophils may be present but not predominant cell Aveolar spaces have proteinaceous fluid exudate -> walls lined by hyaline membrane

Caused by Mycoplasma pneumoniae common in children and young adults in environmental or closed community (school, military camp, prison) Viruses (influenza, RSV, adenovirus, rhinovirus, rubeola, rubella) -infections in the upper respiratory tract and more severe lower respiratory tract infection Deverlopment of pneumoniae -> other conditions -> illness, alcoholsma and malnutrition

Few symptoms -> headache, fever, muscle aches Low mortality rate Secondary bacterial infection by staphylococcus, streptococcus can sometime occur following a viral infection

A) acute pneumonia -> congested septal capillaries and extensive neutrophil exudation into aveoli corresponds to early red hepatization B) Early organization of inta-aveolar exudate seen in areas to be streaming through the pores of Kohn (arrow) C) Advanced organizing pneumonia featuring transformation of sxudates to firbomyoid masses richly infiltrated by macrophages and fibroblasts. Red hepatization Macrophages ingesting red blood cells

Influenza Many types of sub types of influenza flu virus - most in upper respiratory tract -> debilitated patients and epidemics -> lowere respiratory tract Type A Influenza virus -> major cause of pandemic and epidemic influenza infections - avian virus that recently crossed into mammals - birds have greatest number and range -> risk for avian flu generally low for most humans -> dont infect - Avian Flu Influenza A (H5N1) o Influenza virus type A subtype very contagious among birds -> deadly o H5N1 generally does not infect people -> infections have occurred in humans Most related to humans having

Description Incubation period (1-4 days) Single infected person can transmit to a large volume of people Few hours after infection -> 100+ incomplete virons demonstrated by EM at periphery of cytoplasm below cell memrbrane

Histology Mucosal hyperemia and edema w/ monomucelar cell infiltration of submucosa and mucous secretion Swelling may obstruct sinuses or Eustachian tube -> 2nd bacterial infection Laryngobronchitis and bronchiolitis -> swelling of the vocal, impaired bronchociliary function, 2nd bacterial infection w. marked suppuration

Etiologies Common in young, elderly and those with chronic cardio-pulmonary diseases Vaccine -> 70% protection - not effective against recently evolved strains -> evolution outpaces vaccine formation rate - primarily influenza A -> changes surface Ags so new vaccine produced yearly

Clinical Couse/Complications Clinical Course Fever, myalgia, headache, and pharyngitis Cough, severe cases have prostration Coryza (runny nose) but more common of common cold infections Sever symptoms subside in 7 days Complications Viral pneumoiae - severe or fatal - invades lung -> no signs until DAD

direct or close contact with H5N1 infected poultry or surfaces SARS (Severe Acute Respiratory Syndrome) Reported in 2002 -> China since spread

Small and terminal airway obstruction -> focal atelectasis or extensive lung damage -> healing with fibrosis Diffuse alveolar damage (DAD) and respiratory distress -> death

Nosocomial Pnuemoniae

Gm rods Staph. aureus

Spreads via respirtory droplets produced by coughing or sneezing in infected person by close contact Dx: detection of Ab to virus or detection of virus by PCR Frequent in patients with diseases requiring mechanical ventilation, immunosupression, prolonged antibiotic therapy or invasive access devices Aspiration of gastric contents either well unconscious of during repeat vomiting

occurs Bacterial pneumoniae -Haemophilius influenzae - Staph. Aureus -Strep. pneumoniae Fever > 100.4 F (38 C) Headache, general malaise , aches Symptoms usually mild -> after few days patient may develop dry nonproductive cough, dyspnea, pneumoniae develops

Aspiration pneumoniae

Mixtures of aerobes and anaerobic organisms

Gastric acid causes extensive necrosis

Course fulimant -> signfcant mortality Survivors have lung abscesses

Chronic pneumoniae Pneumoniae in immuncompromised

Protoypes such as TB, histoplasmosis, blastcomycosis, coccidiomycosis Pneumocystis Casued by opportunistic Cytamegalovirus, etc. organisms or agents causing pneumoniae in other wise healty agents Influenza

Frequent cause of morbidity and mortality

Cold Cause

50% of colds are caused by one of more than 100 rhinoviruses. The One of the strains of three types of influenza viruses (A, B or C), with A rest are caused by five other groups of viruses. responsible for flu epidemics

Fever Sneezing, nasal congestion Sore throat Cough Sweating Muscle aches Malaise Fatigue Headache Complications Onset Duration Contagious

Rare in adults; is usually not higher than 38,5 degrees Celsius.

High fever (often reaching 39 to 40 degrees Celsius) with chills, lasting three to four days. Fever is highest in children and least marked in the elderly. In some cases. In some cases. A severe, dry cough, accompanied by a sore chest at first. It often develops into a productive cough. Common an related to the fever. Can be severe. The "I've-been-run-over-by-a-bus" feeling. Can be severe. Can be severe and may last three to four weeks. Often severe. Influenza often leads to serious secondary bacterial infections such as pneumonia or bronchitis in high-risk groups including infants, the elderly and immune-compromised people. Symptoms can occur abruptly. It is sometimes possible to pinpoint the exact hour that the symptoms began. Severe symptoms may last four to seven days; cough and fatigue may linger for two to three weeks. A person can spread the virus almost immediately after exposure, and for as long as the viral symptoms last.

Prominent Usually begins with or is accompanied by a sore throat. If the cold leads to a cough, it's usually a mild to moderate dry hacking cough, often worse at night or on rising in the morning. Unusual. Unusual. Sometimes, but only mild. May feel tired, but never exhausted. Sometimes. Seldom > secondary bacterial infections. Can worsen existing chronic bronchitis. Some of the cold viruses can cause pneumonia or croup in young infants. Slow onset of illness over days. Symptoms usually clear within two to four days. Generally a cold should be completely over in four to 10 days. A person can spread the virus one to three days before first symptoms, and then for as long as the symptoms last.

Lung abscesses - Poly microbial and commonly associated with infections due to Staph. Aureus, anaerobic and aerobic streptococci and many G- organisms o Anaerobic organisms from oral cavity are isolated in 60% of cases - Occur in assosciation with : o Aspiration of infective material o Previous pulmonary bacterial infection o Septic embolism -> from right side of the heart -> effective endocarditis in IV drug abuser o Neoplasms with obstruction of bronchopulmonary segment o Spread from neighboring site or hematogenous seeding of lung by pyogenic organisms - After several weeks of attempted repair -> layers of granulation tissue and dense scar formation on outer margins of abscess - Over time granulation tissue will attempt to fill in cavity -> residual retracted fibrous tissue o Old cavity may persist -> site of secondary fungal colonization (fungus ball)

Lung Carcinoma Common cause of cancer carcinoma world wide 13% of cancer diagnosis - decline in men death rates, women death rate - annual deaths >160,000

Pathogensis/ Etiology Carincogenic effects of ciagarette smoking (90% cancers) - greatest assoc. with squamos and small cell - 10 fold greater risk-> >2 packs/day for several year 60 fold greater risk - Cessation risk to baseline levels Women have susceptibility to carcinogens in tobacco then men Passive smoking risk to 2x that of nonsmokers Adults b/w 40 and 70 Exposure to industrial hazards - doses ionizing radiation - Uranium - Asbestos -> exposure in cirgarette smoker > 55 x greater than non-exposed non smokers - Radon Air pollution -> indoor low level exposure to radon Pathogensis Series of genetic abnormalties -> transforamition of norm. bronchi epithelial cells into malignant neoplastic cells Gentics -> cumulative genetic alteration in lung cells -> neoplastic phenotype - deleted or inactivated tumor suppressor genes -> p53, RB, multiple loci o chromosome 3, p16INK4a - dominant assoc. oncogenes in lung and cancer -> cMYC, K-RAS, mutant EGFR, HER-2/neu

Morphology Sequential changes in epithelium of respiratory tract in smokers -> carcinoma Carinogens intiators (polycyclic hydrocarbons) and promoters (phenol derivatives) identified in cigarette smoke -> also linked to development of cancer of the oropharynx, larynx, esophagus, panacres, uterine cervix, kidney, urothelium

Complications/ Clinical presentation 1 year survival 40-50% overall survivial 15%

Carcinoma Precursor lesions and classifications Precursor lesion - basal cell hyperplasia - Squamos cell dysplasia and carcinoma in situ - Atypical adenomatous hyperplasia - Diffuse idiopathic pulmonary neurendocrine cell hyperplasia Clinically clustered into two groups - Based on therapeutic plans and likelihood of metasis: small cell, non-small cell carcinoma Major histologic variants

- Adnocarcinoma 25-40% - Small cell carcinoma 20-40% - Large cell 10-15% - Bronchioaveolar <10% Addl tumors, carcinoid, adenosquamos carcinoma Morphology: Tumors arise from bronchi near hilum of lung -> form intraluminal masses, invade bronchial mucosa -> large masses grow near lung parenchyma Small number arise from periphery from alveolar septal cells or terminal bronchioles -> adenocarcinomas Squamos cell carcinoma Men associated with smoking Thickening of the bronchial mucosa (beginning) Progression -> irregular elevated or erosive lesion -> exophytic or endophytic Large tumors -> area of hemorrhage or necrosis Spread to involve lymph, liver, adrenals, brain, bone Histo: variable differentiation some show keratinzation, intracellular bridge to less well differentiated tumors (arises from metaplasia -> bronchial epithelium b/c norm. physiology columnar - Adjacent mucosa -> metaplasia, dysplasia, carcinoma in situ

Well differentiated

Poorly differentiated Adenocarcinoma Most common type of lung cancer in women and non smokers (75% to the 98% in squamo/small cell carcinoma) Peripherally located -> associated with areas of scarring Histology varies from poorly differentiated to well differentiated Majority are mucin secreting tumors Grow more slowly than squamos cell tumors -> early metastsis Occur as module or area resembling pneumonic consolidation

Bronchioaveolar carcinoma

Arise from terminal bronchioloaveolar region May orginate in bronchiolar cells, clara cells or type

Nonmucinous tumors tend not to spread throughout the lungs; mucinous tumors spread -> multiple

II pneumocytes

Growth along pre-existing structures w/o destruction of alveolar archeitecture

nodules

Small cell carcinoma

Aggressive tumor Strong association with cigarette smoking

Centrally and peripherally arises Small round, oval or spindle shaped w/ scant cytoplasm. Ill-defined cell borders, granular (salt and pepper), nuclear chromatin pattern Resemble lymphocytes but 2x larger High mitotic index Extensive necrosis EM shows dense core neurosecretory granules similar to those in Kulchitsky cells along bronchial epithelium

Metastasize widely -> incurable with surgery -> chemotherapy

Large cell carcinoma

Undifferentiated lesions with large nuclei, prominent nucleoli and moderate cytoplasm Undifferentiated squamos cell or adenocarcinoma Variant tumor has organoid nesting of cells -> resembling neuroendocrine differntation

A) squamous b) adenocarcinoma c) small cell d) large cell

Horners Syndrome

Assosciated with tumor involving the superior pulmonary sulcus (pancoast tumor) -true pancoast extends through the visceral pleura into parietal pleura and chest wall -> often accompanied by destruction of 1st and 2nd ribs

Papillary constriction, enopthalamos [retraction of eyeball] and ptosis [drooping of upper eyelid], anihydrosis casued by invasion of cervical plexus

Superior vena cava syndrome

Dx: chest x ray and other imaging studies, sputum cytology, endoscopy with examination of bronchial washings, bronchial biopsy Overall all 5yr survivial = 15% - mean survivial for small cell carcinaoma is 1 year

PE revels facial ad upper extremity edema

Poor course -> insidious nature of neoplasm Often discovered after spreading to other sites Usually in the 6th decade Symptoms - cough - weight loss and poor appetite - dyspnea - hemoptysis - wheezing - discomfort during breathing - chest pain - symptoms of pneumonia (fever and mucus producing cough) - discomfort during swallowing - hoarseness

Secretory

Assoc. with

Soft tissue masses at the apex of the right lung associated with destruction of some of the posterior portion of the right 3rd and 4th ribs, lymphadenopathy at the right, tracheobronchial angle, calcifications over the hila and in left mid zone are assumed to be old TB Other paraneoplastic syndromes

paraneoplastic syndromes

-small cell carcinoma o ADH induced hypernatremia due to inappropriate ADH secretion o ACTH produing Cushings syndrome Squamos cell carcinoma o Parathormone, parathyroid hormone related peptide, prostglandins E, and some cytokines all implicated in hyerpcalcemia often seen with lung cancer Calcitonin -> hypocalcemia Gonadotrophs -> gynecomastic Serotonin and bradykinin -> carcinoid syndrome Derived from neuroendocrine cells and >1 to 5% of lung tumors Affects younger patients Low grade malignancy

Lambert Eaton syndrome o Resembles myasthenia gravis with muscle weakness caused by autoantibodies -> neuronal calcium channel - Peripheral neuropathy - Acanthosis nigricans - Leukemoid reaction Finger clubbing (hypertrophic osteoarthritis)

Carcinoid Tumor

Central or peripheral arising to mainstem bronchus projecting into lumen Subclassified as typical and atypical (more likely to metastasize) Histology: Trabecular, palidasing ribbon or rosettelike clusters of cells separated by delicate fibrovascualr structure - Cells are uniform with dense core granules on EM, containing serotonin neuron specific enolase calcitonin and other peptides - Low mitotic index atypical tumors greater number of mitoses , more cellular variability, more tendency for tumor necrosis and spread

Clinical features Related to intraluminal growth pattern, metasis and secretory activities - Most dont metastasize or have secretory activity - Most have benign course with cure by resection Present with cough, hemoptysis, pneumonia, bronchiectasis, atelectasis Secretions may cause diarrhea and intermittent flushing, cyanosis

Metastatic tumor Lung is most common site of metastaic neoplasms Carcinomas and sarcomas spread to involve the lung Variable morphology -> usually with discrete nodules scattered throughout the lobes Carcinoma of the larynx Most common in men > 40 More common in blacks than whites ratio of 3:5:1 Nearly all cases in cigarette smokers Alcohol and asbestos exposure -> contributing factors

95% are squamos cell carcinoma 60-75% grow directly on vocal cords Other sites are supraglottic and subglottic Present as persistent hoarseness Early diagnosis and prompt therapy -> cure 5year survival rate > 80% for lesions on true cords, 50% for suprglottic 1/3 of patients die of cancer related deaths, either secondary respiratory tract infections. Caxechia assosciated with wide spread metastsis Pleural lesions Effusions are common -> hydrostatic pressure, vascular permeability, oncotic pressure, lymphatic drainage Character -> serofibrinous with lung, inflammation, collage, vascular disease Uremia, supprative with adjacent pneumonia, hemorrhagic with neoplasm Varibale signs and symptomc include dyspnear, tachnypnea, chest pain with decreased breath sounds over effusion Hydrothorax with CHF Hemothorax with rupture vessel or trauma Chylothora -> lymphatic obstruction and leakage of lymph Empyema -> pus in the pleural cavity usually from spread of infection to pleura from lungs or extension through diaphragm Pneumothorax -> air in pleural cavity; may be spontaneous (idiopathic or rupture of emphysematous bulla) traumatic Variable prognosis, dependent on cause Pleura Tumors are most often metastatic involvement from lung or breast Benging tumor is from fibroma often attached to pleural surface by pedicel - distinguished from malignant mesothelium by CD34+, keratin negative reactions - no relationship to asbestos exposure Malignant mesotheliom - increases incidence in people with heavy asbestos exposure wit latency period of 25-45 years b/w exposure and tumor development