PULM Week 3 Flashcards
what are the 4 stages of bacterial lobar pneumonia
- Congestion–> intracellular alveolar fluid, few neutrophils, often numerous bacteria
- Red Hepatization–> “like liver;” massive intra-alveolar neutrophils with RBCs and fibrin
- Grey hepatization–> macrophages replace neutrophils, and ingest debris
- Resolution–> but may have complications
what is broncho-pneumonia?
PATCHY, infective consolidation of the lung in predominantly LOBAR distribution
common especially in hospitalized patients and as a terminal event complicating systemic illness
usually BILATERAL
pre-existing infective bronchitis spreads to cause bronchiolitis and extends to involve adjacent lung parenchyma
what is interstitial pneumonia?
infectious causes = viruses, rickettsia, chlamydia, mycoplasm, PCP
thickened alveolar walls are heavily infiltrated with mononuclear leukocytes in contrast to intra-alveolar PMN exudate of bacterial pneumonia
large spectrum of presentations–> extreme is ARDS
what are some complications that can arise due to pneumonia
- bacterial dissemination–> bacteremia resulting in meningitis, endocarditis, systemic pyogenic abscesses
- lung abscess formation–> pulmonary parenchymal destruction and suppuration (classically associated with S. aureus/anaerobes)
- empyema–> extension of inflammation to pleural cavity
- endocarditis
- death
**clinical picture is dramatically altered by administration of appropriate antibiotics
pathogenesis of bacterial pneumonia
- pyogenic bacterium–> acute inflammation–> intra-alveolar pneumonia (LOBAR/broncho)
- viral–> infect type I pneumocytes–> alveolar injury–> INTERSTITIAL pneumonia
- TB/fungal–> GRANULOMATOUS inflammation (caseous or necrotizing)
what is lobar pneumonia
characterized by area of UNIFORM consolidation of part of a lobe or the entire lobe
commonest type of CAP
majority are due to s. pneumo
lobar distribution is a function of the virulence of the bacterial organism and the vulnerability of the host
what is ARDS?
“acute respiratory distress syndrome”
clinical and pathological end result of severe, acute, alveolar injury–> severe diffuse damage to alveolar capillary wall
rapid onset of severe life threatening respiratory insufficiency–> may progress to extra-pulmonary multisystem organ failure
diffuse alveolar damage is the pathological abnormality that results in clinical ARDS
initial injury can be to capillary endothelium or alveolus but eventually both are affected–> final common pathway leads to predictable histological pathway associated with respiratory failure
etiology of ARDS
complication of many diverse conditions, including direct lung injury or a complication of systemic disorders
direct lung injury that can leads to ARDS–> diffuse pulmonary infection (i.e virus, pneumonia, SARS), inhaled irritant or gastric aspiration
systemic injuries that lead to ARDS can include septic shock, shock associated with trauma (i.e burns, pancreatitis, narcotic overdose), and near drowning
150 000 cases in the US/year
50% mortality–> often related to severe underlying pathology–> most survivors recover fully but some may have disability due to scarring
what is the name of the model used to describe the pathogenesis of ARDS
gram negative sepsis model
what are the two stages in the pathogenesis of ARDS
exudative and healing/organizing
describe the pathogenesis of ARDS
type I pneumocyte damage and endothelial cell damage–> inflammation–> fibroblast proliferation–> collagen deposition
this all leads to type II pneumocyte proliferation and interstitial fibrosis
describe the exudative phase of ARDS pathogenesis
- ENDOTOXIN induces release of TNF alpha from monocytes and alveolar macrophages
- this causes upregulation of ADHESION molecules and release of cytokines from endothelial cells
- this causes activation of the ALTERNATE COMPLEMENT pathways to generate C5a which upregulates adhesion molecules on neutrophils
- adhesion molecule upregulation results in “sticking” of neutrophils to endothelium and sequestration of neutrophils in lung capillaries
- sequestered neutrophils–> activated neutrophils–> release oxygen free radicals, proteases, leukotriene, prostaglandins, all of which damage the endothelium and increase permeability and trigger coagulation
- this results in NECROSIS of endo and epithelial cells
what is the path of activated neutrophils to necrosis of tissue in ARDS?
diffuse alveolar damage–> decreased lung surfactant concentration–> alveolar collapse
formation of the HYALINE MEMBRANE (pink on histo section)
“point of no return cascade”
describe the organizing/healing phase of ARDS pathogenesis
type II pneumocyte proliferation and intersitial fibrosis
ARDS pathological microscopic findings
early exudative phase characterized by interstitial and alveolar edema, cell necrosis and hyaline membrane formation
organizing healing phase characterized by alveoli lined by regenerating type II pneumocytes with intra-alveolar and interstitial fibrous tissue formation
ARDS pathological macroscopic findings
lungs are HEAVY and FIRM (may have superimposed pneumonia on top of ARDS)
what cells secrete surfactant to prevent alveolar collapse
type II pneumocytes
what is the importance of elastin in the airways?
ubiquitous in the lung–> found in close association with collagen and proteoglycans
elastin and collagen fibers from alveoli, bronchi, interlobar septae and visceral pleura all have connections with fibers of the pulmonary arteries and therefore there is a continuum of fibers throughout the lung such that any force exerted on the parenchyma is distributed throughout the whole organ
elastin fibers also provide sufficient elasticity to allow lungs to return to original volume during expiration (compliance)
function of alveolar macrophages
dust cells
lung is rich with dust cells that pass freely from circulation through interstitial space and through the alveolar epithelium to lie on the alveolar surface
active in combatting infection and scavenging foregin bodies
have primary and secondary lysosomes in cytoplasm
irregular margins represent the many pseudopods and microvilli
what is tuberculosis
communicable chronic GRANULOMATOUS disease caused by mycobacterium tuberculosis
usually involves the lung but can affect any organ in the body
typically granulomas undergo CASEOUS NECROSIS
**6% of all deaths worldwide–> most common cause of death from a single infectious agent
how does infection differ from disease
infection implies SEEDING of a focus with organisms which may or may not cause clinically significant tissue damage or disease
reservoir of the organism is found in humans with infection or disease
how is TB spread
inhalation of airborne organisms in aerosols from infected persons or by exposure to aerosolized contaminated secretions
pathogenesis of TB
cell mediated immunity confers resistance to the organism resulting in development of tissue hypersensitivity to tubercular antigens
pathological features of TB
CASEATING GRANULOMAS and TISSUE CAVITATION
result of destructive tissue hypersensitivity that constitutes the host immune response
immune response comes at the cost of hypersensitivity and accompanying tissue damage
describe primary TB
develops in previously unexposed person–> source is exogenous (i.e inhaled bacilli implanted in distal air spaces of lower part of upper lobe or upper part of lower lobe, close to pleura)
as sensitization develops, a GHON FOCUS forms, and necrosis develops–> tubercle bacilli, either free or within macrophages, will drain to regional lymph nodes and also caseate–> once regional lymph nodes are involved the complex is called a GHON COMPLEX–> hematological and lymphatic spread to the body (first few weeks… seeding but no infection)
in 95% of cases, cell mediated immunity controls the infection
Ghon complex undergoes progressive FIBROSIS followed by CALCIFICATION–> foci of scarring may harbour viable bacilli for years–> prone to reactivation if immune compromised
what is progressive primary TB
uncommon
continues on from initial TB
occurs in immunecompromised states (AIDS, malnourishment, elderly, Inuit)
may result in miliary TB or TB meningitis
