Path Flashcards
atelectasis
collapse of previously inflated lung resulting in relatively airless pulmonary parenchyma
ARDS/DAD
HYALINE MEMBRANE
EDEMA
emphysema
loss of elastic recoil of lung: abnormal PERMANENT enlargement of airspaces by destruction of their walls
centriacinar emphysema
HEAVY SMOKING
UPPER lobes
panacinar emphysema
alpha1-antitrypsin deficiency
LOWER lobes
paraseptal emphysema
underlies SPONTANEOUS PNEUMOTHORAX
chronic bronchitis
persistant cough with sputum at least 3 months in at least 2 consecutive years
increased REID index
large airway: submucosal gland hypertrophy
small airway: increase goblet cells
peribronchial fibrosis
asthma
chronic inflammatory disorder of airways: increased responsiveness to stimuli
inflammation damages and perpetuates bronchoconstriction
overinflation, mucous plugs
EOSINOPHILS
CURSCHMANN SPIRAL
CARCOT LYDEN crystals
bronchiectasis
permanent airway dilation with smooth muscle and elastic tissue destruction
repeated airway obstruction and inflammation lead to fibrosis
obstructive lung disease
lung does not empty
list of obstructive lung diseases (4)
emphysema
chronic bronchitis
asthma
bronchiectasis
Two functions of type II pneumocyte
surfactant
repair
resorption atelectasis
airway obstruction by mucous plugs, tumor
resorption of trapped O2 in dependent alveoli
mediastinum shifts TOWARD affected lung
compression atelectasis
filling of pleural cavity by tumor, blood, air
compression of pulmonary tissue
mediastinum shifts AWAY from affected lung
contraction atelectasis
fibrotic lung or pleura
prevention of full expansion
NOT reversible
COPD
combination of emphysema and chronic bronchitis
alpha1- antitrypsin deficiency
PANACINAR emphysema
LIVER CIRRHOSIS: PAS positive hyaline globules (misfolded protein accumulates in ER of hepatocytes)
alpha 1 antitrypsin
neutralize proteases (elastase) released by inflammatory cells
PiZZ
A1AT deficiency homozygote at risk for panacean emphysema and liver cirrhosis
PiMZ
A1AT deficiency heterozygote: low levels of A1AT; ok unless smoke
bullae
markedly enlarged subpleural airspaces
prone to rupture: results in pneumothorax
What is the role of smoking in chronic bronchitis?
chronic irritation from inhalation results in mucous hyper secretion
Reid index
ratio of thickness of the mucous gland layer to the thickness of the wall between the epithelial basement membrane and cartilage
normal: 0.4
increased in: chronic bronchitis
extrinsic asthma
type I hypersensitivity reaction to inhaled allergen
IgE
MAST cells
intrinsic asthma
non-immunologic reaction: precipitated by respiratory infection, stress, exercise, cold, drugs, etc.
histological aspects of asthma
- thickened BM
- submucosal gland hypertrophy
- bronchial wall smooth muscle hypertrophy
- eosinophils
causes of bronchiectasis
- cystic fibrosis
- Kartagener
- necrotizing pneumonia
- bronchial obstruction
cystic fibrosis
chloride transport defect results in thick obstructive secretions
Kartagener
immotile cilia syndromes: interferes with bacterial clearance
tracheoesophageal (T-E) Fistula
failure of fetal respiratory tract to separate from GI tract
FOREGUT
alveolar stages
- glandular: thick walls, lots of CT, cuboidal
- saccular: transition to flat, type I and type 2 alveolar cells
- alveolar stage: reduction of interstitial tissue and increase capillaries
NOT histologically mature until: age 8
rhinitis
inflammation of nasal mucosa
rhinovirus: common cold or allergic (type I)
repeated: NASAL POLYPS
nasal polyps
edematous, inflamed nasal mucosa
causes: repeated rhinitis, CF, aspirin intolerant asthma
aspirin intolerant asthma
asthma
aspirin induced bronchospasm
nasal polyps
angiofibroma
benign tumor of the nasal mucosa composed of large blood vessels and fibrous tissue
Sx: profuse epitaxis
chronic interstitial/restrictive lung disease
heterogenous group
dyspnea and reduced lung capacity
results in diffuse scarring
honeycomb on CT
END STAGE of restrictive diseases
idiopathic pulmonary fibrosis (IPF)
patchy INTERSTITIAL fibrosis, lower lobe sub pleural distribution
Masson bodies, collagenized areas, mild lymphocytic inflammation
Sx: dyspnea on exertion, dry cough
Tx: NONE
must rule out secondary cause
TGF-B from injured pneumocytes: fibrosis
usual interstitial pneumonia (UIP): histologically
pneumoconioses
non-neoplastic lung rxn to inhaled dusts (coal, silica, asbestos, berylliosis, etc.)
hypersensitivity pneumonitis
prolonged exposure to inhaled dusts
type IV sensitivity: T cells (NO eosinophils)
GRANULOMA
to prevent fibrosis: remove environmental irritant
ex: farmer’s lung, bird fancier’s lung, etc.
interstitial fibrosis
Masson body
fibroblast foci
believed to be sites of recent injury
collagen vascular disease-associated lung disease
RA, scleroderma, mixed connective tissue disease
UIP histologically
cryptogenic organizing pneumonia (COP)
INTRA-ALVEOLAR: CT in bronchioles, alveolar ducts, and alveoli (all SAME AGE)
Tx: steroids
simple coal workers pneumoconiosis (CWP)
UPPER lobe
little or no pulm. dysfunction
coal dust macules (dust accumulation adjacent to respiratory bronchioles with/out dilated adjacent alveoli (emphysema)) and nodules (carbon-laden macrophages with collagen)
complicated coal workers pneumoconiosis (CWP)/ progressive massive fibrosis
lung function compromised
develops in those with simple CWP
black scars composed of pigment and dense collagen
associated with: RA
anthracosis
CWP
carbonaceous pigment in macrophages that accumulates in CT along lymphatics and in lymph tissue
silicosis
SANDBLASTERS, MINE WORKERS, STONE cutters
progressive nodular fibrosis
UPPER lobes and hilar nodes
macrophages: ingest silica and release fibrogenic mediators
collagenous nodules, birefringent silica particles
increased susceptibility to TB
beryllium
SPACE industry, MINERS
non-caseating GRANULOMA: lung, hilar lymph nodes, organs
increased chance of lung CA
non-neoplastic asbestos-related diseases
- diffuse pleural fibrosis
- benign pleural effusions
- plerual plaques
- parenchymal interstitial fibrosis (Asbestosis)
MORE COMMON than cancer
parenchymal interstitial fibrosis (asbestosis)
Sx: slowly progressive dyspnea
heavy ASBESTOS exposure: 20 yr latency
initial injury: respiratory bronchioles and alveolar ducts: results in fibrosis of adjacent alveoli
drug/radiation pneumonitis
chemo (busulfan) or radiation to chest
sarcoidosis
AA female south non-caseating GRANULOMA (hilar lymph nodes, lung, skin) Sx: dyspnea, cough, non specific Tx: steroids CD4:CD8 ratio greater than 2.5 disease of EXCLUSION
desquamative interstitial pneumonia (DIP)
SMOKING
peribronchiolar
Tx: stop smoking, steroids
respiratory bronchiolitis
SMOKING
peribronchiolar
Tx: stop smoking, steroids
pulmonary langerhans cell histiocytosis
YOUNG SMOKERS rare Tx: quit BRAF mutation leads to alveolar damage and airway destruction Langerin, S-100, CD1a NO CD68
pulmonary alveolar proteinosis
rare
defect in GM-CSF or macrophages: accumulation of surfactant
can be autoimmune, secondary (malignancy or immunodeficiency), or hereditary (infants)
pneumocystis jirovecii
yeast fungus
IMMUNOCOMPROMISED: HIV
pulmonary embolism
most from deep leg vein thrombi
immobilization, hypercoaguable states
adequate CV function: bronchial arterial supply sufficient to sustain distal lung tissue
inadequate pulmonary circulation (cardiac or pulmonary disease): infarction (10%)
secondary pulmonary hypertension causes
cardiopulmonary conditions that increase pulmonary blood flow/pressure/vascular resistance or left heart resistance to flow
- chronic obstructive or interstitial lung disease
- cardiac disease
- recurrent thromboemboli
primary pulmonary hypertension
female, 20s-40s
Sx: dyspnea, fatigue
inactivating BMPR2 mutation: proliferation of vascular sm. muscle
How does chronic obstructive or interstitial lung disease lead to pulmonary HTN?
hypoxia and fewer alveolar capillaries from parenchymal destruction leads to increase pulmonary arterial resistance and pressure
How does cardiac disease lead to pulmonary HTN?
mitral stenosis causes elevated left atrial pressure that increases pulmonary venous and arterial pressure
How do recurrent pulmonary thromboemboli lead to pulmonary HTN?
decrease in functional area of pulmonary vascular bed leads to increased vascular resistance
good pasture
male, teens, smokers
autoimmune disorder with Ab to alpha-3 chain of collagen IV
destruction of BM in kidney glomeruli and lung alveoli
Sx: pulmonary hemorrhage
idiopathic pulmonary hemosiderosis
pulmonary hemorrhage disease
lupus erythematosus
vasculitis with pulmonary hemorrhage
wegener granulomatosis (polyangiitis with granulomatosis)
med. to small vessel vasculitis
Sx: necrotizing granulomas of respiratory tract, glomerulonephritis, pulmonary hemorrhage
hemodynamic pulmonary edema causes
- increased hydrostatic pressure: left heart failure
2. decreased oncotic pressure: liver disease
causes of pulmonary edema due to microvascular injury
- infection
- inhaled smoke and other gases
- shock
acute lung injury/ ARDS (acute respiratory distress syndrome)
rapid onset of severe life-threatening respiratory insufficiency and hypoxia
caused by diffuse alveolar capillary damage
DECREASE COMPLIANCE
HIGH GRADE INFLAMMATION
high MORTALITY
HYALINE MEMBRANES, WHITE OUT CXR, non cardiogenic EDEMA
Sx: hypoxemia, cyanosis
Tx: underlying cause, PEEP, PRONE ventilation, diuresis as needed, NO (improves oxygenation, does NOT improve mortality)
SHUNT: does not respond to O2
complication: interstitial fibrosis (reduced DLCO), pneumothorax
death is due to: MULTI ORGAN FAILURE
diffuse alveolar damage (DAD)
histological manifestation of ARDS and neonatal RDS
neonatal RDS
preterm infants with deficient surfactant (28 weeks production, 34 weeks sufficient surfactant)
L:S ratio greater than 2: have enough surfactant
cause: premature, C-section, DM in mom
Sx: hypoxemia, cyanosis, tachypnea, increased respiratory effort, GROUND GLASS CXR
complications: patent ductus arteriosus, necrotizing enterocolitis
complications of supplemental O2: blindness, bronchopulmonary dysplasia
Direct lung injury causes of ARDS
DIRECT injury:
- infection (pneumonia/ aspiration)
- injury: trauma, near drowning, burns
- inhaled irritants: O2 toxicity, smoke
- fat emboli
pathophysiology of acute lung injury
- INFLAMMATORY MEDIATORS: macrophages release: IL-8, IL-1 and TNF
- NEUTROPHILS move from vasculature into alveolar space
- INCREASED PERMEABILITY: neutrophils release leukotrienes, oxidants, proteases, PAF that cause endothelial and epithelial injury
- PROTEIN RICH EDEMA in airspace, SURFACTANT INACTIVATION, hyaline membrane formation
- macrophage TGF-B and PDGF stimulate fibroblasts
What happens in acute stage of acute lung injury?
endothelial: vasculature leakage
epithelial: cell sloughing
edema, hyaline membrane, atelectasis
What happens in the organizing stage of acute lung injury?
type II cell proliferation
interstitial inflammation: recovery, interstitial fibrosis, death
congestion stage of pneumonia
vascular engorgement and edema
few PMN
numerous bacteria
red hepatization stage of pneumonia
massive congestion
abundant PMNs and fibrin
gray hepatization stage of pneumonia
disintegration of RBC, macrophages
fibrinopurulent exudate
resolution stage of pneumonia
enzymatic digestion
resorption by macrophages
aspiration pneumonia
risk: alcoholic, comatose, drugs
anaerobic from oropharynx
RIGHT LOWER lobe abscess
bronchogenic cysts
arise from abnormal detachments of primitive foregut and usually present with compression of nearby structures or are found incidentally
pulmonary sequestration
discrete area of lung tissue that lacks connection to the airway system and has an abnormal blood supply arising from the aorta
hamartoma
benign nodules of overgrowth mature connective tissue (in normal location)
karyotype: 6p21 or 12q14-15
causes of primary lung carcinoma
- smoking (number 1)
- industrial: radiation, uranium
- asbestos: synergistic with smoking
- air pollution
- radon (number 2)
small cell carcinoma
presents at advanced stage
Tx: chemo, radiaiton
Non-small cell carcinoma
more resistant to chemo
Tx: surgery with/out chemo, radiation
operate on I, II, IIIA (not past lung, involves structures that can be removed)
IIIb, IV (out of chest): not operable
lung adenocarcimona
most common: female, non-smoker PERIPHERAL GLANDS, MUCIN sometimes pneumonia like consolidation lepidic pattern horner syndrome sometimes stain: TTF-1 positive, CK-7 positive
squamous cell carcinoma
males, SMOKERS CENTRAL central necrosis/CAVITATION KERATIN PEARLS, INTRACELLULAR BRIDGES PTHrP: HYPERCALCEMIA Stain: p40
large cell lung carcinoma
PERIPHERAL
large nuclei with prominent nucleoli and vesicular chromatin
POOR PROGNOSIS
small cell lung carcinoma
SMOKING
high grade NEUROENDOCRINE
CENTRAL: with mediastinal lymphadenopathy
AGGRESSIVE, RAPID growth with widespread metastases
more chemo/radiosensitive: good response, but comes back (high mortality)
abundant mitoses, small blue cells with scant cytoplasm and granular (SALT and PEPPER) chromatin
ADH: hyponatremia
ATCH: cushings
Lambert-Eaton syndrome: muscle weakness
stain: CHROMOGRANIN, SYNAPTOPHYSIN
MEDICAL disease, limited vs extensive
carcinoid tumor
50-70, often incidental finding low grade NEUROENDOCRINE carcinoma central or peripheral bland cells with granular chromatin, dense core granules CHROMOGRANIN
what does prognosis of lung carcinoma depend on?
stage (TMN)
T: size (invasion of pleura, bronchus, etc., distance from carina)
N: nodes
M: metastases
K-ras mutation
25% of ADENOCARCINOMA in SMOKERS
EGFR mutations
10-25% of ADENOCARCINOMAS
non-smoker, FEMALE, ASIAN
ALK mutations
ADENOCARCINOMA
mucin stain?
local effects of lung cancer spread
- tumor obstruction of airway: pneumonia, abscess, collapse
- recurrent laryngeal nerve invasion: hoarse
- superior vena cava compression: superior vena cava syndrome
- sympathetic ganglion invasion: horner syndrome
horner syndrome
PANCOAST tumor: just above lung
sympathetic nerve ganglion invasion
Sx: one sided: mild ptosis (drooping), miosis, lack of sweating, red half of face
Lambert-Eaton syndrome
Ab to voltage gated Ca channels
muscle weakness
common origins of metastatic lung cancer
MOST COMMON site of metastatic tumors
carcinoma (lymph): breast, colon, lung, melanoma
sarcomas: blood
common origins of metastatic pleural tumors
MORE common than primary
lung, breast
malignant mesothelioma
parietal or visceral pleura ASBESTOS long latency:20 + years SIMIAN virus 40 assoc. Chromsome deletions: 1p, 3p, 6q, 9p, 22q common Sx: chest pain, dyspnea, effusion rapid course: 50% die in less than a year Tx: surgery, chemo/radiation
histologic types of malignant mesothelioma
- epithelioid (most common): can resemble metastatic adenocarcinoma
- sarcomatoid: resembles sarcoma
- biphasic: mix of both
how do you distinguish mesothelioma from adenocarcinoma?
- histochemical stain
- immunohistochemical stain
- electron microscopy
mesothelioma 1. hyaluronic acid 2. calretinin 3. long slender microvilli Adenocarcinoma 1. mucin 2. CEA (carcinoembryonic antigen) 3. stubby microvillus rootlets
nasopharyngeal carcinoma
malignant epithelial cancer
EBV association
cervical lymph nodes are often involved
laryngeal papilloma
benign: papillary lesion of vocal cord
HPV 6 and 11
single in adults
multiple in children
laryngeal carcinoma
squamous cell carcinoma arising from vocal cord
risk: ALCOHOL, TOBACCO
Primary lung cancer vs. Secondary lung cancer
primary: one nodule
secondary: multiple nodules
lung adenocarcinoma: colonic adenocarcinoma metastasis: taller longer cells, dirty necrosis
CK20
stain
positive if origin of cancer is below the waist
ex: colonic that metastasize to lung
CK7
stain
positive if origin of cancer is above the waist
ex: originate from lung
p40
stain
squamous cell lung carcinoma
CA19
stain
pancreatic adenocarcinoma
CDX2
stain
colonic adenocarcinoma
performance status
poor (status 3 or 4): can’t tolerate surgery, chemo, or radio
respectability also depends on if patient can survive removal of whole lobe or the lung
0: perfect
1: less than 25% have to rest/nap during day
2: less than 50%
3: less than 75%
4: have to rest entire day
5: dead
Tx of NSCLC by stage of cancer
I: surgery
II: surgery (radiation if unable to under go surgery), then chemo (adjuvant)
III: radiation and chemo
IV: chemo, immune Rx, palliative radiation
adjuvant tx
surgery, then chemo
neoadjuvant tx
radiation to shrink, then surgery
Indirect lung injury causes of ARDS
INDIRECT injury:
- SEPSIS
- chemical injury: heroin overdose
- shock (hypoperfusion)
- hematologic: multiple transfusions: TRALI (transfusion related acute lung injury)
- cardiopulmonary bypass
- acute pancreatitis
Causes of ARDS in unknown category
- hypersensitivity rxn
2. uremia
4 stages of ARDS and their time frames
- exudative (acute): 0-4 days
- proliferative: 4-8 days
- fibrotic: greater than 8 days
- recovery
factors that increase the risk of death in ARDS
- chronic liver disease
- non-pulmonary organ dysfunction
- sepsis
- old age
When is pneumothorax after ARDS most prevalent?
after 2 weeks of ARDS onset
