Resp Path 4 - Pulmonary Infection and Neoplasia - Galbraith Flashcards
Five things that if compromised, can allow pulmonary infections to occur.
- Cough reflex - decreased = aspiration
- Ciliary function - impaired = 3. mucus-stasis
- Decreased phagocytic function of pulmonary macrophages
- Pulmonary edema/congestion
Definition of pneumonia.
Any infection of the lung parenchyma.
What 2 lab testing characteristics help differentiate between bacterial pneumonia and viral pneumonia?
In bacterial pneumo:
Higher CRP
Higher procalcitonin levels
Absent splenic function predisposes toward what type of infection?
Encapsulated bacterial infection
Seven bacterial causes of Community-Acquired Acute Pneumonias
**Strep pneumoniae Haemophilus influenzae Moraxella catarrhalis Staph aureus Klebsiella pneumoniae Pseudomonas aeruginosa Legionella pneumophilia
- G+, lancet shape diplo
- Elongated DIPLOCOCCI in SPUTUM
- Most common cause of CA-pneumonia
Strep pneumoniae characteristics
- Gram (-)
- ENCAPSULATED type B most virulent
- Kids and COPD
Haemophilus influenzae characteristics
Pediatrics - bacterial pneumonia (meningitis and LRIs)
- Adults - Most common cause of bacterial acute EXACERBATION OF COPD.
- Virulence factors like adhesive pili and IgA degredation by protease.
- G- cocci
- Elderly - exacerbation of COPD
- Pediatric - OTITIS MEDIA
Moraxella catarrhalis characteristics
- G+ cocci
- Imp cause of SECONDARY BACTERIAL PNEUMONIA, after a viral infection
- High risk of complications (abscess, empyema)
- Think: IV drug abusers and endocarditis
Staph aureus characteristics
- Most common G- bacterial pneumonia (rod)
- CHRONIC ALCOHOLICS, MALNOURISHED, DM
Klebsiella pneumoniae
- Imp cause of pneumo in CF and neutropenic pts
- Hematogenous spread!
- **Nosocomial infection
Pseudomonas aeruginosa characteristics
- Water tanks»_space; aerolization
- Pontiac fever and Leginnaires’ disease
- Immunosuppressed, chronic disease
- URINE LEGIONELLA ANTIGEN for diagnosis
Legionella pneumophila characteristics
- in children and YA
- a dry cough that won’t go away
Mycoplasma pneumonia characteristics
What is the main morphologic change in lung tissue due to bacterial invasion?
CONSOLIDATION, as alveoli fill with inflammatory cells and exudate.
Two main patterns of consolidation in the lungs.
- Bronchopneumonia
2. Lobar pneumonia
What type of consolidation pattern is this?
- PATCHY exudative consolidation of lung parenchyma.
What else is characteristic of this?
Bronchopneumonia
- Focal, consolidated areas that may coalesce
- BASAL, MULTIlobar and frequently BILATERAL.
What type of consolidation pattern is this?
- Consolidation occupies an ENTIRE LOBE
Lobar pneumonia
List the four stages of lobar pneumonia
- Congestion
- Red hepatization
- Gray hepatization
- Resolution
1/4 Stage of Lobar Pneumonia and characteristics
- CONGESTION due to vascular engorgement and with fluid and bacteria
2/4 Stage of Lobar Pneumonia and characteristics
- RED HEPATIZATION - full of neutrophils, RBCs, fibrin
3/4 Stage of Lobar Pneumonia and characteristics
- GREY HEPATIZATION - fibrinosuppurative material, RBC breakdown, early org.
4/4 Stage of Lobar Pneumonia and characteristics
- Resolution - organizing fibrosis admixed with macrophages resorption of debri and enzymatic digestion of exudates.
What does resolution normally result in ?
Restoration of normal lung structure and function. But organization with fibrous scarring can occur.
What is empyema?
Fibrinopurulent material.
Expansion of infection into pleural space
s/s of CA-acute pneumonia
- Abrupt fever
- Shaking chills
- Productive cough
- Rust-colored sputum
Look for what in PE to suggest pleural involvement in CA-acute pneumonia.
Friction rub and pleuritic chest pain
Potential complications of CA-acute pneumonia.
Systemic dissemination causing: endocarditis, meningitis, suppurative arthritis, metastatic abscesses.
Galbr: abscess, empyema (pleural involvement), bacteremia
Difference in CXR between lobar and bronchpneumonia.
Lobar - obque lobe
Bronch - focal opacities
What is the common pathogenic mechanism between CA-Atypical (Viral and Mycoplasmal) Pneumonias?
Attachment of organisms to epithelial cells, followed by necrosis and inflammation.
- In alveoli, causes fluid transudation.
- In upper airways - loss of mucociliary clearance of resp epithelium=secondary bacterial (super) infection predisposition.
Morphology of CA-Atypical pneumonias (differing characteristics from bacterial)
- Patchy or lobar congestion WITHOUT CONSOLIDATION
- Widened, EDEMATOUS alveolar walls with LYMPHOCYTES AND MACROPHAGES
- HYALINE MEMBRANES reflex DAD
Five common causes of CA-Viral Pneumonia
- INFLUENZA A (B and C)
- RSV
- Human metapneumovirus
- Adenovirus
- Rhinovirus
Cause of major influenza epidemics (antigenic drift - “drift away form host antibodies”) and pandemics (antigenic SHIFT “recombo of viral RNA during replication”).
Influenza A infecting humans, pigs, birds, horses.
What are the two important viral proteins that determine the influenza A virus subtype?
- Hemagglutinin (H1-H3) - binds to respiratory epithelial cells, allowing cellular infection
- Neuraminidase (N1-N2) - allows new virion release
What part of respiratory tract does influenza involve? And once it infects the epithelium, what does it cause?
- URT = facilitation of spread from person to person.
- After infection occurs, it causes: intraalveolar fluid accumulation, cell death, inflammation.
Human metapnumovirus characteristics.
Cause bronchiolitis and pneumonia in very young and very old.
- Causes 20% of outpatient visits for pediatric acuteRTIs
SARS characteristics
Coronavirus. Different because it infects upperRT AND LOWER RESPIRATORY TREE»_space; systemic spread.
Fatal cases = lungs show DAD with multinucleated giant cells.
3 common causes of Chronic Pneumonia.
- General characteristics
Localized granilomatous inflammation in inmmunocompromised pts.
- Histoplasmosis
- Blastomycosis
- Coccidioidomycosis
Intra-macrophage fungal pathogen
Inhaled bird/bat droppings
histoplasma capsulatum
MS/OH rivers, think…
Histoplasmosis
4 clinical presentations of histoplasmosis.
- Self limited pulm infection!
- Chronic, prgressive lung infeciton (apical, night sweats, Fever, cough)
- Extrapulmonary involvement (liver, adrenals, mediastinum, meninges)
- Wide dissemination
Morphologic findings in histoplasmosis.
What stain used for dx?
- Caseating granulomas
- Coagulative necrosis that may resolve by fibrosis and concentric calcification
- SILVER STAIN shows 3-5micro-m yeast.
If histoplasmosis is disseminated, what two morphologic things are seen?
- Organisms found within clusters of macrophages (liver, adrenals, etc)
- NO CASEATING GRANULOMAS
General characteristics of blastomycosis.
- Caused by Blastomyces dermatidis.
Central/SW USA soil think…
Canada, Mexico, ME, Africa, India
Blastomycosis
Three forms of blastomycosis
Pulmonary
Disseminated
Primary cutaneous (erythema nodosum, erythema multiforme)
Morphology of blastomycosis
Granulomas are___
- 5-15micro-m thick
- DOUBLE-WALLED YEAST WITH VISIBLE NUCLEUS
-… suppurative
Broad Based Budding, think…
Blastomycosis
General characteristics of coccidiomycosis
- Caused by Coccidioides immitis
SW/W US and Mexico, think…
Coccidiomycosis
Spherules are what.
think what disease…
Contain endospores. Are in lung granulomas
Coccidiomycosis
Morphology of Coccidiomycosis
- 20-60micro-m
- Taken up by macrophages»_space; resist killing
- SPHERULES
fever, cough, detectable lung granuloma, pleuritic pain, skin lesions = what specific manifestation of
coccidiomycosis
San Joaquin Valley Fever
Defining characteristics of Hospital Acquired Pneumonia - high risk situation, most common G+ and G-
- Very high risk with mechanical ventilation
- G-positive cocci: Staph aureus and Strep pneumonia
- G-negative rods: enterobacteriaceae and Pseudomonas
Defining characteristics of Aspiration Pneumonia
- People with abnormal gag and swallowing reflexes
- Pneumonia dt chemical (gastric acid) and bacterial (oral flora)
- Often aerobic, NECROTIZING, fulminant
- Complication: Lung ABSCESS
Difference between Aspiration Pneumonia and Microaspiration
- Aspiration - frequent cause of death.
- Microaspiration - frequent in ppl with GERD. See NON-NECROTIZING granulomas with multinucleated giant cell rxn. Can exacerbate asthma, interstital fibrosis, lung rejection.
Main opportunistic infections that cause life-threatening pneumonias in immunocompromised hosts (3 for diffuse infiltrates; 5 for focal infiltrates)
Diffuse - CMV, Pneumocystis jiroveci, drug rxn
Focal - G- bacteria, Staph aureus, Aspergillus, Candida, Malignancy
HIV related Pulmonary disease: most common bugs at CD4 counts (200+, 50-200, less than 50)
200+ = bacterial and TB
50-200 = Pneumocystis
Less than 50 = CMV and MAC
Also: all the “normal” pneumonia bugs (strep pneumo, staph aureaus, H. flu)
Lung abscess defintion
Local suppurative process that produces necrosis of lung tissue
Etiology of lung abscess
- Oropharyngeal surgery, dental, sinobronchial infection, bronchiectasis, etc.
- Nugs: Staph aureaus, G-, anaerobic (Bacteroides, Fusobac, peptococcus)
Five ways causative organisms are introduced to the lungs to cause abscesses.
- Aspiration of infective material (most frequent)
- Antecedent primary lung infectino (s aureus, K pneumoniae) **Post-transplant
- Septic embolism from infected thrombo or R-sided endocarditis
- Obstructive neoplasia - postobstructive pneumonia
- Direct traumatic punctures or spread of infection from adjacent organs
What do lung abscesses contain?
Pus and air.
Complications of lung abscesses
- *Development of BRAIN ABSCESSES or MENINGITIS from septic emboli.
- Secondary amyloidosis, hemorrhage, infection into pleural cavity
When are lung transplants performed?
Emphysema, idiopathic pulmonary fibrosis, CF, primary pulmonary HTN
3 potential complications of lung transplant
- Infection in first few weeks posttransplant (Aspergillus, Candida at bronchial anastomotic site)
- Acute rejection
- Chronic rejection 3-5years posttransplant. Fibrosis (broncholitis obliterans)
What genetic polymorphisms result in increased susceptibility to tobacco smoke?
Polymorphisms of p-450 mono-oxygenase
Environmental exposures that cause lung cancer.
- ASBESTOS esp + smoking
- Radiation: uranium/radon
- Occupational: Vinyl chloride
Three precursor lesions that may progress to malignancy
- Squamous dysplasia and carcinoma in situ
- Atypical adenomatous hyperplasia
- Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia.
What carcinoma has the strongest association with smoking?
Other characteristics?
Squamous Cell Carcinoma
- p53 mutations/overexpression
- Begins in CENTRAL lung/hilar region from segmental bronchi
Morphologic progression of squamous cell carcinoma.
- Shows intrabronchial **PRECURSOR LESION (squamous metaplasia, dysplasia, and CARCINOMA IN SITU)
Keratin Pearls, think what?
PTH-rp, causing hypocalcemia without feedback… think what?
Squamous Cell Carcinoma
Smoking with in situ component, think what neoplasm?
Squamous Cell Carcinoma
No smoking, no in situ component, think what neoplasm?
Adencocarcinoma (met)
3 P’s of adenocarcinoma
Pleural surface
Peripheral (differentiates this from carcinoid)
Pucker Pleural surface
Mutations in adenocarcinoma
Gain of function mutations involving GF receptor pathways:
- EGFR, ALK (ROS, MET, RET)
- KRAS (resistant to therapy)
Adenocarcinoma precursor lesions (2)
- Atypical adenomatous hyperplasia (less than 5mm)
2. Adenocarcinoma in situ (less than 3cm) PRODUCING MUCIN
What positive staining test helps determine if adenocarcinoma is from the lung?
TTF-1
“Oat Cell”
SMOKING!!! withOUT in situ
small cell carcinoma
Characteristics of small cell carcinoma - genetics, aggressiveness, size
- TP53 and RB mutations
- Aggressive and high fatality
What area of the lung do small cell carcinomas generally arise from? And what type of cells?
- Central OR peripheral
- From neuroendocrine cells in bronchial epithelium
Describe morphology of small cell carcinoma
- Small cells with little cytoplasm
- Huge nuclei with MOLDING and ABSENT NUCLEOLI
- Marked necrosis
Paraneoplastic syndrome assoc with small cell carcinoma
ADH or ACTH (SIADH and Cushings)
Metastasis of lung cancer
ADRENALS, kidney, brain, bone
- Hematogenous spread within lymphatics
Name of tumor that arises from BRONCHIAL neuroendocrine cells.
Is this malignant or benign?
Carcinoid tumor - low grade malignant. Classified typical (p53 mutation) or atypical (BCL2 and MAX abnormal expression)
What are Pancoast tumors?
Lung tumors than invade neural structures around trachea»_space; cervical sympathetic plexus = HORNER SYNDROME
What are tumorlets?
Small, benign hyperplastic nests of neuroendocrine cells seen adjacent to chronic inflammation or scarring.
Morphology of carcinoids
- Intrabronchial, highly vascular, polyploid masses less than 3-4cm.
- Neurosecratory granules seen. with immunostaining.
- Propensity for LYMPHATIC INVASION
What is carcinoid syndrome?
Results in what s/s?
- Tumor makes SEROTONIN, look for 5-HIAA in urine
- FLUSHING, DIARRHEA, CYANOSIS
Organoid nests, think what?
Well organized appearance of carcinoids.
What are symptoms of carcinoids related to?
Centrally located/Bronchial obstruction - cough, hemoptysis, impaired drainage.
Prognosis for carcinoid.
Typical - Relatively benign with 95% 5 year survival
Atypical - 70% 5 year survival
Tumors met to the lung
Breast, colon, kidney, prostate, bladder.
2 types of Pleural Tumors
- Solitary Fibrous Tumor (nonivasive, fibrosing, rarely malignant.)
- Malignant mesothelioma
Malignant mesothelioma is highly associated with exposure to what?
ASBESTOS, compounded by smoking
Morphology of Malignant mesothelioma
Spreads diffusely over entire lung surface - forms a compressive sheath
- Epithelioid Pattern
- Sarcomatoid Pattern
Epithelioid pattern of Malignant mesothelioma
Epithelium like cells forming tubules and papillary projections. Distinctive from adenocarcinoma bc of WT-1, CK5/6, and calretinin and long, selder microvilli.
Sarcomatoid pattern of Malignant mesothelioma
Malignant, SPINDLE shaped cells resembling fibrosarcoma
s/s of Malignant mesothelioma
chest pain, dyspnea, recurrent plerual effusion.
Most common mutation in Malignant mesothelioma.
homozygous deletion of p16, seem in 80%
Survival rate of Malignant mesothelioma
few survive longer than 2 years.
