Adult Respiratory Distress Syndrome (ARDS)
Bilateral pulmonary infiltrates on CXR
Microscopy - Diffuse Alveolar Damage (DAD)
extremely thin (2 um), gas exchange surface between alveoli air sacs and the blood, endothelial cells of the capillaries and epithelial cells of the alveoli, allows O2 in and CO2 out
seen in granulomatous disease such as Sarcoidosis
pink eosinophilic star shaped inclusion in giant cells
Chronic inflammatory disease - REVERSIBLE
Atopic, Non-atopic, Drug induced, Occupational
Loss of lung volume due to alveolar collapse
Resorption (obstruction), Compression (pleural effusion), Contraction (scarring)
Chronic Obstructive Lung Diseases such as Emphysema, air trapping in the lungs that cannot be exhaled, and increased intra-thoracic pressure allows chest wall to expand, hyperinflation results in barrel shaped torso.
an irregular bulge in the plasma membrane
Description of a patient with Chronic Bronchitis
Blue due to cyanosis and bloated due to low respiratory drive, less respiration, less effort
a cyst within the airways
can have compression, infection, hemorrhage, rupture
Focal regions of emphysema with no discernible septa/wall that measure greater than 1 cm
Permanent dilation of bronchioles secondary to destruction of the supporting tissue.
Obstruction (tumor or foreign body), Congenital (CF or Kartagener's), Necrotizing Pneumonia (S. aureus & Klebsiella)
Productive cough for 3 consecutive months or more in a 2 year period.
Hypertrophy or seromucous glands and goblet cells
Proliferation of fibroblasts in the airway tubes, not just the alveoli space. Inflammation and fibrosis.
Many causes, dry cough, FEV1 ~20% !!
malignant neoplasm of the lung arising from the epithelium of the bronchus or bronchiole, may grow into the lumen and obstruct the airway, spreads to lymph nodes
Chronic Obstructive Pulmonary Disease (COPD)
4th leading cause of deaths in the US, 3rd world wide.
Obstruction to airflow, FEV1/FVC greatly reduced.
Asthma (reversible), chronic bronchitis, emphysema, bronchiectasis.
round, well circumscribed nodule, < 4 cm
usually an incidental finding on CXR
most commonly a benign tumor but 10-20 % of cases it is malignant (older adults and smokers)
region of lung tissue (normally spongy) that is filled with fluid, swelling or hardening of the normally aerated lung
opaque on CXR
enlargement of the right ventricle of the heart due to pulmonary disease/pulmonary hypertension
leads to right heart failure and death
Diffuse Alveolar Damage (DAD)
Usually seen in ARDS, TRALI, AIP
1) exudative - alveoli become flooded with transudate
2) hyaline membrane form (pink and lining air sacs)
3) organizing phase
abnormal permanent air space enlargement DISTAL to the terminal bronchioles
destruction of alveoli air sacs WITHOUT FIBROSIS
collection of pus in the pleura around the lung
Extrinsic Allergic Aveolitis
Hypersensitivity Pneumonia, immunological response to extrinsic antigen, can be Type III or IV HSR, usually inhaled antigen (hot tubs, humidifiers, etc.)
Restrictive lung disease, ground glass opacity on CT
1) airway centered process
2) chronic inflammatory infiltrate
3) organizing pneumonia
4) giant cells
5) poorly formed non-necrotizing granuloma
parenchymal lesion + lymph node in TB infection
1-1.5 cm inflammatory consolidation (granuloma) with central caseous necrosis, associated lymphatics and lymph node (node can also show necrosis)
Primary Immune Disease affecting the lungs and the kidneys. Diffuse Alveolar Hemorrhage Syndrome. Antibodies targeted to the alpha 3 chain of type IV collagen deposit along the BM. Type II HSR. Shows a liner deposition pattern on immunofluorescence.
blood accumulation on the pleural cavity
Heart Failure Cell
Hemosiderin containing macrophages in the alveoli.
Left heart failure -> pulmonary edema -> high pressure causes RBCs to pass through the vascular wall into the alveoli -> taken up by macrophages
coughing up blood
anytime vessels leak into the alveoli air sacs or into the airway tubes
pulmonary fibrosis, scarring of the lungs, gross appearance of lungs resemble a honeycomb
usually due to interstitial lung disease (viral, autoimmune) but can be idiopathic
cervical sympathetic plexus damage (usually due to compression from a tumor of the lung)
ptosis, meiosis, anhydrosis
ipsilateral enopthalmus (sinking in of the eye)
acellular proteinaceous material, glass like and pink on H&E or bright pink on PAS
characteristic of DAD (associated with ARDS)
diffuse inflammation of lung parenchyma
cytokines released by epithelium -> PMNs and T Cells
hyaline membrane formation in alveolar wall
serous fluid accumulation in the pleural cavity
Hypertrophic Pulmonary Osteoarthropathy
secondary to lung cancer (adenocarcinoma and all non-small cell lung cancer)
clubbing & increased bone deposition on long bones
painful swollen joints (ankles)
(also Bamberger-Marie Syndrome)
Idiopathic Interstitial Pneumonia
Restrictive Lung Diseases
Desquamative Interstitial Pneumonia (DIP
DAD (in ARDS)
Non-specific Interstitial Pneumonia (NSIP)
Usual Interstitial Pneumonia (IPF, Collagen Vascular Disease CVD, drug toxicity, Pneumoconiosis)
Organizing Pneumonia (COP)
Lymphoid Interstitial Pneumonia (LIP)
Idiopathic Pulmonary Fibrosis (IPF)
chronic progressive lung disease (relentless)
bilateral interstitial fibrosis
mean survival, 3 years (transplant)
Non-small Cell Lung Cancer
70-75% of lung cancers
Squamous Cell Carcinoma
Large Cell Carcinoma
Can usually be surgically resected if caught early
Bronchiolitis Obliterans Organizing Pneumonia (BOOP) when there is a known cause (CVD, pneumonia, transplant immune response)
Cryptogenic Organizing Pneumoia (COP) when unknown cause
Inflammation of bronchioles & surrounding lung tissue, persistent alveolar exudate undergoes organization & fibrosis, architecture in tact
Fibrosis in alveoli, alveolar ducts and bronchioles forms Masson Bodies
apical lung tumor, can spread to ribs and vertebrae
Compression of blood vessels causing edema
Compress of recurrent laryngeal nerve, hoarseness
Compress esophagus, difficulty swallowing
Obstruct Thoracic Duct, chylothorax (lymph in pleural cavity)
Compress SVC, head and neck swelling
consequence of cancer in the body but not due to the local presence of cancer cells - mediated by hormones or immune response
caused by small cell lung cancer
patients with emphysema
They don't show hypoxic symptoms and cyanosis until late so they are pink
Thin & frail from increased effort of breathing
Pursed lips from creating back pressure to exhale
multiple lumen formed in a small artery at the branch point from a larger artery
proliferation of vasculature (looks re-canalized)
occur in pulmonary hypertension
Pneumothorax Pulmonary Edema
Injury to the lung that can cause pulmonary edema
blockage of the main artery of the lung or one of its branches by a substance traveling in the blood stream
(usually thromboembolism, but also air, fat, amniotic fluid, septic, IV drugs, bone marrow)
Pulmonary Veno-occlusive Disease (PVOD)
Right upper lobe tumor of the lung can cause compression of the SVC
Noticeable swelling of the face in the morning with resolution upon being upright.
Congestion of the head, face, and neck results (can cause cerebral edema, rarely)
clicking, rattling, or cracking noises made by the lungs on inhalation
Ratio of the glands to the total wall thickness
Normally: glands/wall < 40%
In chronic bronchitis Reid Index reaches 50% or more
Restrictive Lung Disease
Heterogenous group of disorders characterized by a decreased FVC.
Interstitial, bilateral, patchy, fibrosis, decreased compliance, V/Q mismatch, pulmonary hypertension, cor pulmonale
low pitched continuous sounds heard on auscultation usually due to bronchial secretions
Large embolus lodged in both sides of the main pulmonary artery bifurcation.
Results in sudden death, acute right heart failure.
calcium and protein inclusions within Langhan's giant cells as part of a granuloma
Usually in sarcoidosis or hypersensitivity pneumonia
Severe Acute Respiratory Syndrome
China, Hong Kong, Singapore, Canada
2003 Outbreak, 8,000 sick and 700 deaths
US not infected (only 8 people)
Small Airways Disease
in chronic obstructive lung diseases
Emphysema - respiratory bronchioles & alveoli destruction
Chronic Bronchitis - goblet cell metaplasia, mucous plugs, inflammation and fibrosis
severe prolonged asthma attack, unresponsive to therapy, respiratory failure and death results
hyperinflation of lungs all the way around mediastinum on autopsy
collection of air or gas in the pleural space
one-way-valve in area of damaged tissue allows air in but not out, compresses lung, tracheal deviation and mediastinal deviation
What mediates pain in pulmonary disease?
irritation of nerves in the pleura
What causes a productive cough?
anything that dumps material into the airways (infection, fluid, blood)
What causes a non-productive cough?
irritation of the airways without material inside
usually interstitial disease processes
What causes dyspnea?
any lung pathology!
What causes sputum production?
hypertrophy of mucous glands and goblet cells
fluid extravasation into airways & alveoli
What are the telling signs of cyanosis?
blue coloration, usually in the extremities
clubbing of fingernails
What causes secondary polycythemia?
Overproduction of RBCs due to chronically low O2
High altitude or any cyanotic pulmonary disease (ex. COPD)
Dyspnea when laying flat
Caused by pulmonary edema and left heart failure
Dyspnea that worsens upon standing
Hepatopulmonary syndrome causing dilation of the vessels of the lungs in patients with liver disease
What is normal serum hemoglobin?
13-18 g/dL in men
12-15 g/dL in women
What hemoglobin level defines cyanosis?
> 5 g/dL reduction
What is tactile fremitus?
palpable vibration on the wall of the thorax caused by friction rub between the parietal and visceral pleura
What is bronchophony?
abnormal sound in the lungs
patient repeats ninety-nine or Scooby Doo
What is ergophony?
increased resonance of voice sounds usually due to fibrosis or consolidation in the lungs
high-pitched quality to a person's voice
What radiographic studies are used in evaluating lung diseases?
CXR (AP or lateral)
CT scan (look for ground glass opacity)
PET scan (shows fluoro-deoxy glucose uptake in metabolically active tissue, cancers)
Bronchography and Arteriography
What are the factors evaluated in pulmonary function tests (spirometry)?
TLC (total lung capacity, volume at max inhale)
RV (residual volume, volume after max exhale)
FVC (forced vital capacity, max exhale)
FEV (forced expiratory volume, exhale over time)
FEF 25-75% (forced expiratory flow, midway exhale)
What is a good measure of small airway disease?
How is pulmonary function changed in obstructive lung disease?
FEV1:FVC ratio is REDUCED <70% of normal
FVC slightly reduced <80% of normal
FEV1 greatly reduced
How is pulmonary function changed in restrictive lung disease?
NORMAL FEV1:FVC ratio
What are normal arterial blood gas measurements?
PaO2 75-100 mmHg
PaCO2 35-45 mmHg
What are the three types of Atelectasis?
Resorption, Compression, Contraction
Describe Resorption Atelectasis:
Obstruction of airway (mucous, etc.), no air flow to affected alveoli, all of the O2 within them is absorbed into the blood since there is no obstruction to perfusion, alveoli collapse
Where does the trachea shift in resorption atelectasis?
towards the affected side
Describe Compression Atelectasis:
pleural cavity compressed by fluid, exudate, tumor, blood or air causing the collapse of affected alveoli
Where does the trachea shift in compression atelectasis?
away from the affected side
Describe Contraction Atelectasis:
scarring in the lung causes fibrosis and pulling inward of the alveoli air sacs
Which atelectasis is not reversible?
What is the histological name for ARDS?
Diffuse Alveolar Damage (DAD)
What are the direct causes of ARDS?
pneumonia, aspiration, emboli, inhalation injury, drowning, oxygen toxicity
What are the indirect causes of ARDS?
sepsis, trauma with shock, acute pancreatitis, severe burns, transfusion of blood products (TRALI), uremia, drugs
What does a CXR of ARDS look like?
bilateral pulmonary infiltrates
complete white out
Does ARDS respond to oxygen therapy?
What changes occur to the lung tissue in ARDS?
alveolar-capillary membrane compromise (alveolar epithelium and capillary endothelium)
blood gas barrier damage (loss of diffusion)
loss of surfactant (type II cell damage)
increased vascular permeability (fibrin and inflammatory mediators leak out of vessels)
What are the two phases in ARDS?
Acute (exudative) 0-7 days
Organizing (proliferative) 1-3 weeks
How do the lungs feel in the acute phase of ARDS?
like a rubber eraser
heavy and firm
What characterizes the acute phase of ARDS?
interstitial and intra-alveolar edema & hemorrhage
necrosis and sloughing off of epithelial cells
What characterizes the chronic phase of ARDS?
proliferation of type II pneumocytes (round up and protrude into the lumen) & surfactant production
organizing fibrin exudates, fibrosis, septal thickening
What is the mortality rate of ARDS?
What therapy is given to ARDS patients?
What factors indicate a poorer ARDS prognosis?
multisystem organ failure
What causes respiratory compromise after the cute phase in ARDS?
If normal function returns after ARDS, when does this occur?
What are the 4 obstructive lung diseases?
What is significant about the epidemiology of COPD (stats)?
4th leading cause of death in the US
3rd leading cause of death in the world
Which of the obstructive diseases is reversible?
What part of the airways is affected by Emphysema?
Alveoli air sacs and Respiratory Bronchioles
small airways distal to the terminal bronchioles
What is the main cause of the tissue destruction in Emphysema?
Protease: Anti-protease imbalance
and impaired tissue repair
What is the process of damage in Emphysema?
inhalation of toxic agents -> inflammatory response (PMNs, Macs, T cells) -> Elastase, Cytokines, Oxidant stress, Failure of Anti-oxidants and Anti-proteases, Epithelial cell injury and proteolysis of ECM, destruction of alveoli
What are the 4 types of Emphysema?
What does Emphysema look like on gross appearance?
What does Emphysema look like in histological appearance?
free floating alveolar septa
Destruction of elastin, collapse and trap air on exhalation
Describe Centrilobular Emphysema:
Upper lung zones
Respiratory bronchioles are affected
Describe Panlobular Emphysema:
Alpha 1 AT Deficiency
Lower lung zones
Distal to respiratory bronchioles affected
Almost no normal alveoli
What is Alpha 1 Anti-trypsin Deficiency?
Chromosome 14 mutation
Pi gene: mutant PiZZ and normal PiMM
Misfolded Anti-trypsin protein can't leave hepatocyte
Protein accumulates in the liver, chronic liver disease
1% of all Emphysema
(can also be TGFB gene mutations or MMP gene mutations)
Describe Septal Emphysema:
Margins of the lung, sub pleura, upper lobes
May form bullae (large holes in alveoli)
can lead to pneumothorax - atelctasis
Describe Irregular Emphysema:
Surrounding a scar, the scar contracts and pulls alveoli air sacs open (only in extensive scarring)
How does a patient with Emphysema present?
Barrel chest, weak and skinny, hunched forward, dyspnea, prolonged expiration, pursed lips
blood gases normal & not cyanotic until late
flat diaphragm on CXR
How is Chronic Bronchitis Diagnosed?
productive cough for > 3 consecutive months in 2 years
What is the major defining feature of Chronic Bronchitis?
Buckets of Sputum
Hypersecretion of Mucous
REALLY productive cough
Who gets Chronic Bronchitis?
What are typical inhaled irritants causing Chronic Bronchitis?
cigarette smoke, sulphur dioxide SO2, nitrogen dioxide NO2
Are there eosinophils present in Chronic Bronchitis?
Inhaled irritants induce what 3 things?
Hypertrophy of seromucous glands (Reid Index >50%)
Increased goblet cells (in bronchioles, metaplasia)
Infiltrate of PMNs, Macs, T Cells
What is the disease process of the small airways in Chronic Bronchitis?
goblet cell metaplasia in bronchioles
smooth muscle hypertrophy (narrowing airway lumen)
What two coexisting conditions complicate Chronic Bronchitis?
What causes the airway obstruction and collapse in exhalation in Chronic Bronchitis?
ongoing fibrosis and obstruction from inflammation
(not the mucous plugging)
What is the gross presentation of the lungs in Chronic Bronchitis?
Large Airways: Hyperemic, red, and swollen, mucinous and mucopurulent secretions causing mucous plugging, hypertrophy & hyperplasia of glands, increased Reid Index and inflammatory cells
Small Airways: goblet cell metaplasia, mucous plugging, inflammation and fibrosis
What does the fibrosis lead to?
lumen narrowing and obstruction of air flow
What does a patient with Chronic Bronchitis look like?
Hypoxic, hypercapnic, and cyanotic
Can have many secondary infections (block a tube and get an infection behind it)
Decreased respiratory drive, overweight
Pulmonary Hypertension and Cor Pulmonale
Does COPD affect males or females more?
What is responsible for respiratory drive in Chronic Bronchitis patients?
low O2 measured by peripheral chemoreceptors
(chronic hypercapnia has caused decreased sensitivity to low CO2 levels in central chemoreceptors)
What happens if you put a patient with Chronic Bronchitis on high oxygen therapy?
Depressed respiratory drive, no breathing, suffocation
The O2 sensors that are now responsible for respiratory drive will sense increased O2 and cause cessation of breathing but they are still hypercapnic
What defines Asthma?
Anatomical airways narrowing
Chronic inflammatory disease
What are the 4 types of Asthma?
Drug Induced (aspirin)
What is the defining cell type in Asthma?
Describe Atopic Asthma:
Allergic sensitization, Type I HSR, IgE mediated
Antigen exposure -> IgE crosslinked on Mast cells -> degranulation
What 2 other conditions can patients with Asthma have?
What type of T Cell is involved and what cytokines?
IL4 - stimulates IgE production (more cross linking)
IL5 - activates eosinophils
IL10 - increase Th2, stop Th1 proliferation
IL13 - mucous production & IgE production by B cells
What characterizes the Early Phase of Atopic Asthma?
Vagal stimulation -> bronchoconstriction
(immediate, vascular mediated)
What characterizes the Late Phase of Atopic Asthma?
Activation of eosinophils, PMNs, and T Cells
Epithelial cells activate and recruit more Th2 cells
(4-24 hours, immune response mediated)
What are some triggers of Asthma?
dust, pollen, animals, foods
What skin test is used to test for allergic reactions to possible antigenic asthma triggers?
Wheal and Flare skin test
Describe Non-atopic Asthma:
serum IgE is NORMAL, no previous sensitization
Inhaled NO2, SO2, or O3
Viral induced mucosal damage lowers vagal threshold
Describe Drug-Induced Asthma:
Caused by Aspirin
Inhibits arachidonic acid COX pathway
Shifts towards Lipoxygenase pathway, produces more Leukotrienes C4, D4, E4 (bronchoconstriction)
What other signs and symptoms present in Drug-Induced Asthma?
recurrent rhinitis, nasal polyps, urticaria (hives), bronchospasm
Describe Occupational Asthma:
REPEATED exposure to fumes, organic dusts, chemical dusts, gases
(epoxy resins, plastics, toluene, cotton, platinum)
Chronic daily exposure causes sensitization
Patient will be better on weekends and vacations
What are 2 defining histological features found in the mucous of asthma patients?
Curschmann Spirals (thin pink curly spirals on H&E)
Leyden Crystals (from MBP produced by eosinophils)
What is the gross appearance of Asthma in the lung?
Occlusion of airways by think mucous
Hyperinflation of the lungs
Edema, patchy epithelial necrosis
How does the lung tissue appear on histology in Asthma?
Mucous plugs with Curschmann spirals and Leyden crystals
Bronchial smooth muscle hypertrophy
basement Membrane thickening
Inflammation with EOSINOPHILS
How dos Asthma present on Spirometry?
FEV1 < 30%
Intervals of normal values between attacks
Chronic condition will show residual respiratory defects even in symptom free intervals
How does Asthma present?
Recurrent sudden attacks of respiratory distress
Hypoxia, hypercapnia, respiratory acidosis
Tightness of chest
Wheezing and Rhonchi
Progressive hyperinflation with air trapping distal to mucous packed bronchi
Attacks last hours and subside (therapy or on own)
What are the three defining signs of any chronic obstructive lung disease?
What is Churg Strauss Disease?
Cutaneous, GI, Renal, and Lung Disease
Allergic Granulomatosis and Angiitis
ANCA-MPO in 50% of cases
Eosinophilia (eosinophils chewing on blood vessels)
Infiltration of vessels and perivascular tissue by eosinophils, small vessel necrotizing vasculitis
Extravascular necrotizing granulomas
Death due to cardiac involvement
What is Brochiectasis?
Permanent dilation of bronchi and bronchioles from destruction of supporting tissue
What 3 things cause Brochiectasis?
Bronchial Obstruction (tumor, foreign body)
Congenital Conditions (CF, Imm. Def., Kartagener's)
Necrotizing Pneumonia (Staph aureus & Klebsiella)
Describe Brochiectasis due to bronchial obstruction:
Obstruction hampers clearance -> Iinfection -> damaged and weakened bronchial walls -> Bronchectasis
What 3 conditions cause Congenital Bronchiectasis?
CF - thick mucous, increased infections
Immune Deficiency (ex. agammaglobulinemia)
Kartagener's Syndrome - abnormal cilia, infections
Describe Bronchiectasis due to infection:
persistent necrotizing infection -> obstructive secretions and airway damage -> peribronchiolar fibrosis -> traction and ectasia -> Bronchiectasis
What does Bronchiectasis look like on gross appearance?
airways going all the way out to the pleural surface, big wide gaping airways
NO hypertrophy or seromucous glands or goblet cells
What are the characteristics of Kartagener's Syndrome?
Primary ciliary dyskenesia
Structural abnormality in dynein arm of cilia
Persistent infections (no much-ciliary escalator)
Infertility in males (non-motile sperm)
Situs Inversus (only in 1/3)
What 3 pulmonary conditions have elevated eosinophil count?
Pulmonary Langerhans Cell Histiocytosis (Burbeck granules, associated with smoking, abnormal proliferation of Langerhans cells in skin and lymph nodes)
What part of the lung parenchyma do Restrictive Lung Diseases usually involve?
What is the defining feature of Restrictive Lung Diseases?
bilateral patchy lung involvement
epithelial and BM cells, collagen, elastin, fibroblasts
dyspnea, hypoxia, increased work to breathe
pulmonary hypertension and cor pulmonale
What are the Fibrosing restrictive lung diseases?
Usual Interstitial Pneumonia (UIP)
Non-specific Interstitial Pneumonia (NSIP)
Cryptogenic Organizing Pneuomia (COP)
Collagen Vascular Diseases (CVD)
Pneumoconiosis (carbon, silica, asbestos)
What are the Granulomatous restrictive lung diseases?
Hypersensitivity Pneumonia (HP)
What are the Eosinophilic restrictive lung diseases?
Chronic Eosinophilic Pneumonia
What are the Smoking-Related restrictive lung diseases?
Desquamating Interstitial Pneumonia (DIP)
Respiratory Bronchiolitis Interstitial Lung Disease (RB-ILD)
What are other extrinsic causes of restrictive lung disease?
Chest wall injury
Neuromuscular diseases (Guillain Barre Syndrome)
What is the Histological name for Idiopathic Pulmonary Fibrosis (IPF)?
Usual Interstitial Pneumonia (UIP)
Does IPF affect males or females more?
What is the IPF/UIP story?
Dr: "I'm an Idiot! What is this really?"
Pathologist: "The Usual"
Dr: "So, its just an old fibrosis and a young fibrosis waking the cobblestone streets along the pleura and the base looking for honeycombs?"
Path: "U guessed it! Mucous filled cystic spaces lined with ciliated respiratory epithelium that don't communicate with airways."
Dr: "Its relentless!"
What age is mostly affected by IPF/UIP?
2/3 are over 60 yrs.
What is the prognosis of IPF/UIP?
3 years men survival
What is required for diagnosis of IPF?
pathology and radiology
What is the gross appearance of IPF/UIP?
Cobblestoned pleural surface
Firm fibrotic parenchyma
Lower lobe on a U-shape and sub pleural
Honeycomb change in lung due to fibrosis
What is the histological appearance of IPF/UIP?
Old fibrosis and young fibrosis at the same time
(spatially and temporally variegated)
Beneath pleura and in interlobular septa
Areas of normal lung
Cystic spaces lined by type II pneumocytes and respiratory epithelium
What is the clinical appearance of IPF/UIP?
Gradual onset of DRY cough and dyspnea
Crackles on inspiration
Progression to cyanosis, cor pulmonale and peripheral edema
When does Non-specific Interstitial Pneumonia (NSIP) usually occur?
men or women, younger
Connective tissue disorders
due to drugs or medications
How is the prognosis of NSIP compared to IPF/UIP?
What does NSIP look like under the microscope?
chicken wire all over the lung (thickened septa)
no spared normal tissue
very uniform (spatially and temporally)
What are the two variants of NSIP?
Cellular - infltrates of lymphocytes
Fibrosing - acellular
What two things does NSIP lack?
NO honeycomb change
NO fibroblast foci
What is the defining histological feature of Cryptogenic Organizing Pneumonia?
fibroblasts around a core of inflammatory cells within the airway
polyploid plugs of loose connective tissue in alveolar ducts, alveoli & bronchioles
What happens to the alveolar architecture in COP?
not destroyed, alveoli remain in tact
When COP is found due to Collagen Vascular Disease (CVD), pneumonia, or it is transplant related what is it called?
Bronchiolitis Obliterans Organizing Pneumonia (BOOP)
(not to be confused with RB-ILD due to smoking characterized by smoker's Macs full of mucous)
What does COP look like on CXR?
patchy peribronchial or subpleural consolidation
What is the story for COP/BOOP?
The COPs find the Body of Masson and begin to solve a cryptic mystery.
If they investigate and find it is due to CVD, pneumonia or transplant, mystery solved, it is BOOP
How is COP treated?
6-12 months of steroids or spontaneous recovery
What are the 4 Collagen Vascular Diseases that usually have pulmonary manifestations?
What patterns of lung involvement are typically seen in CVDs?
Bronchiolitis with fibrosis
Do CVDs involve the pleura?
pleuritis (nerves in pleura will cause chest pain)
pleural nodules, pleural effusion
Who do pulmonary complications from a CVD usually present in?
no other pulmonary circumstances (not smoker, not coal miner, etc.)
What is Hamman Rich Syndrome?
Acute Interstitial Pneumonia (AIP)
What is AIP, in a nutshell?
VERY aggressive form of ILD (interstitial lung disease) that may occur as the acute phase of IPF
What does AIP look like histologically?
DAD and hyaline membranes
it looks like ARDS
What does AIP present like clinically?
go to hospital
end up intubated
What is needed to treat AIP?
What causes AIP?
(like ARDS, with unknown cause, spontaneously occurring)
What happens in Lymphoid Interstitial Pneumonia?
the alveolar septa (interstitium) is expanded by sheets of lymphoid cells, appear very thick
How does LIP look on CT scan?
Ground Glass appearance
(this occurs anytime there is not as much air space)
What disorders is LIP associated with?
Connective tissue diseases, autoimmune diseases, and HIV infection
What is a possible result of LIP?
transformation into a lymphoma
What causes the Ground Glass appearance on CT scan?
tons on full macrophages
What causes Respiratory Bronchiolitis - Interstitial Lung Disease?
What characterizes RB-ILD?
What is seen in the histology of RB-ILD?
Macs filled with mucous and junk in the lumen of the respiratory bronchioles
Peribronchiolar fibrosis (pink collagenous dense scar in the alveolar spaces)
What can be done to treat RB-ILD?
What are reticular nodular opacities?
net or meshwork of ground glass look on a CT scan or on CXR looks like all the interstitium in white/hazy
What causes Desquamative Interstitial Pneumonia?
What does DIP look like on imaging?
TONS of ground glass appearance from accumulation of smoker's macrophages
What characterizes DIP?
filling of alveolar spaces by alveolar macrophages
What defines Sarcoidosis histologically?
Non-necrotizing epithelioid granulomas
in MANY tissues and organs
Who does Sarcoidosis occur in?
young adults < 40 yrs.
Danish, Swedish, African American
What else causes non-necrotizing granulomas?
beryllium, drug reactions (interferon related), mycobacterium (TB is necrotizing)
What is found on CXR that distinguishes Sarcoidosis?
Bilateral Hilar Lymphadenopathy (mediastinal lymphadenopathy)
How do you diagnose Sarcoidosis?
rule everything else out
What causes Sarcoidosis?
Type IV HSR - cell mediated
CD4 T Cells, proliferation of Th1 cells (intra-alveolar and interstitial)
secretion of IFNy and IL-2
What happens in a skin test (PPD) for Candida when there is lots of T Cells activation in Sarcoidosis resulting in peripheral depletion of T Cells?
Describe the histology of Sarcoidosis:
Non-necrotizing granuloma (in a lymphangetic pattern)
Schaumann Bodies (laminated concretion of calcium and protein)
Asteroid Bodies (stellate inclusion in giant cells)
overtime collagen replaces granuloma - hyaline scar
If Sarcoidosis progresses what results in 5-15% of cases?
Diffuse interstitial fibrosis and honeycomb lung
How does Sarcoidosis usually present clinically?
Incidental finding on CXR (bilateral hilar nodes)
Gradual development of respiratory symptoms (SOB, dry cough) and systemic symptoms (fever, fatigue, weight loss, night sweats)
What % of Sarcoidosis shows lung involvement?
What two things can be found to be elevated in serum of patients with Sacoidosis?
Calcium (hypercalcemia due to activation of Vit. D by epithelioid cells)
ACE (angiotensin converting enzyme)
What is the prognosis of Sarcoidosis?
65-70% recovery (spontaneous or with therapy)
20% permanent lung dysfunction
5-15% progressive fibrosis and cor pulmonale
If you give a lung transplant to a Sarcoidosis patient, how likely is it that it will reoccur?
reoccurs in 75% of patients
What syndrome is associated with Sarcoidosis?
Mikulicz Syndrome (Sicca Syndrome)
Dry mouth and Dry eyes
What other organ systems are infected in Sarcoidosis?
Skin (erythema nodosum)
Spleen, Liver, Bone Marrow
What i the other name for Hypersensitivity Pneumonia (HP)?
Extrinsic Allergic Alveolitis
What are the characteristics of HP/EAA?
Airways centered process
Chronic inflammatory infiltrate
Giant cells & poorly formed, non-caseating granuloma
How does HP/EAA occur?
Inhaled organic antigen, often occupational exposure
Can be from a hot tub or humidifier
(can be from bird feathers, so if a bird owner don't just to crypto or histoplasma)
Where is the damage in HP/EAA?
at the alveoli
decreased diffusion capacity (DLCO, larger diffusion barrier due to infiltrate)
decreased lung compliance (restrictive)
decreased total lung volume (TLC)
What does HP/EAA look like on imaging?
ground glass appearance, usually in upper lobes
What HSR occurs in HP/EAA?
Type II or Type III
Immunofluorescence has shown Abs in serum, compliment, and Igs
What are the 3 most common pneumoconiosis?
Coal Workers Pneumoconiosis
What causes Coal Workers Pneumoconiosis?
Inhalation of coal mine dusts
(carbon, trace metals, silica)
What are the three stages of CWP?
What happens in pulmonary anthracosis?
carbon pigment accumulates along the lymphatics
What happens in Simple CWP?
aggregates of dust laden macrophages within a collagen network form coal macules and nodules (black pigment in a meshwork of collagen)
What happens in Complicated CWP?
nodules coalesce to scars causing Progressive Massive Fibrosis
What does CWP tissue look like under polarized light?
often times there will be shiny birefringent silica contaminants
What causes silicosis?
sandblasting and hard-rock mining
What is the pathogenesis in silicosis?
Inhaled silica particles activate pulmonary macrophages -> macrophages release IL-1, TNF, fibronectin, cytokines, and free radicals -> causes fibrogenesis
What is characteristic about silica nodules on microscopy?
eggshell calcifications in lymph nodes
(whorled hyalinized collagen fibers with birefringent silicates - starry sky appearance)
What is the end result of silicosis?
Progressive Massive Fibrosis
hypertension and cor pulmonale
What does silicosis look like on gross appearance?
white collagenous scars and nodular calcifications
When do symptoms present in silicosis?
20-30 years after exposure
progresses even after the cessation of exposure
Susceptibility to what organism is increased in silicosis?
due to inhibited macrophage function - they are too busy gobbling up silica
How does asbestosis present?
parenchymal interstitial fibrosis
What are ferruginous bodies?
asbestos fibers coated with iron from macrophages, turn brown from the hemosiderin pigment
What are the two types of asbestos?
Amphibole (BAD, more pathogenic, needle like)
Non-amphibole (serpentine, curly)
How does the fibrosing process occur in asbestos?
Starts around bronchioles, progresses to involve parenchyma
Begins in lower lung zones and sub-pleura (similar to UIP/IPF)
What are the two key signs of asbestos exposure on examination of the lung tissue?
asbestos bodies and pleural plaques
Risk of what is increased with asbestos exposure?
lung cancer (especially with smoking)
mesothelioma (1000 X normal risk)
WHat does Grade 4 asbestosis look like in lung tissue?
How does asbestosis present clinically?
dyspnea 10-20 yrs. after exposure
can progress to cor pulmonale
What anti-cancer drugs cause interstitial fibrosis of the lung?
What else can cause interstitial fibrosis?
IV heroin (contaminants)
What hereditary disease causes interstitial fibrosis as well as granulomas?
What questions must be asked when evaluating pneumonia?
Age of the patient?
Community or Hospital?
Primary or Secondary?
Immunocompetent or compromised?
Typical or Atypical?
Lobar or Broncho?
Viral or Bacterial?
What are the four stages of pneumonia progression?
Describe Acute Congestion:
Heavy red boggy lungs
Vascular congestion, dilated capillaries
Bacteria multiplying in the alveoli
Fluid exudate, PMNs, and RBCs move into alveoli
Describe Red Hepatization:
Firm rubbery consistency, feels like the liver
Lining of alveoli lost (Type I and II cells)
Alveoli packed with PMNs, fibrin, RBCs
Describe Grey Hepatization:
Dry grey firm lungs when RBCs are lysed
Exudation and hyperemia stop
Fibrin exudate persists in alveoli (balls of fibroblasts in the center of the airspace)
Removal of exudate by enzymatic degradation
Resorbed, engulfed by macrophages or coughed out
Lobar pneumonia - complete resolution, alveoli not damaged
Broncho pneumonia - structural damage
What possible complications can happen with, or after, pneumonia (list 6)?
Organization causing scar tissue
Bronchiolitis Obliterans (fibroblasts in the airway tubes)
What causes Primary Pneumonia? In who?
In healthy people
WHat predisposes someone to Secondary Pneumonia (list 7)?
Pre-existing lung disease (a viral infection)
Bronchial Obstruction (infection behind blocked tube)
Coma (or other neuro deficits, no cough reflex)
What defines Typical Pneumonia?
involves alveoli air sacs (the air space)
What are two types of Typical Pneumonia?
What defines Atypical Pneumonia?
involves the interstitial, alveoli septum (airspaces preserved)
What are the 4 main facets of Lobar Pneumonia?
Spread via Pores of Kohn
What lung structure is NOT involved in Lobar Pneumonia?
What are the 4 facets of Broncho Pneumonia?
Patchy lung involvement
Bronchi, bronchioles, & surrounding alveoli damaged
Normal intervening lung tissue
Less virulent organisms
What are the symptoms likely in Acute Community Acquired Pneumonia?
High fever, shaking, chills, chest pain
What mediates the chest pain felt in acute pneumonia?
involvement of the pleura
parietal pleura innervated via intercostal nerves
What microbe is the most common cause of Acute Community Acquired Pneumonia?
What are the 7 BIG BACTERIA of Acute Community Acquired Pneumonia?
Strep. pneumonia, H. influenza, Moraxella catarrhalis, Staph. aureus, Klebsiella pneumoniae, Psuedomonas aeruginosa, Legionalle pneumophilia
What are the three most likely organisms to cause Otitis Media in children?
Strep. pneumonia, H. influenza, M catarrhalis
What is H. influenza?
G -ve bacteria
What causes influenza?
Orthomyxo virus, ss - RNA virus
Nucleoprotein determines Type A, B, or C
Hemagglutinin & Neuraminidase determine subtype
Variations in H&N, antigenic drift, immune evasion
Type A humans, pigs, horses, and birds
Describe pneumonia from Strep. pneumonia:
Lower lobe or right middle lobe
Underlying chronic disease (COPD, CHF, Diabetes)
Decreased splenic function (Sickle Cell Anemia)
Vaccines given to susceptible persons (young, old, immunosuppressed)
Why is decreased splenic function predisposing to Strep. pneumonia?
Streptococci are Gram + bacteria with capsule, the spleen is needed to kill encapsulated bacteria
Asplenic patients are susceptible to these infections
What do you look for in a sputum sample if you suspect a Strep. pneumonia infection?
Gram + diplococci intracellularly within PMNs
(Strep. pneumonia can be normal flora, so if it a true infection they will be gobbled up by PMNs)
What are the 2 most likely microbes to cause pneumonia in COPD patients?
#1 H. influenza
#2 Moraxella catarrhalis
Who gets pneumonia from H. influenza:
Occurs in COPD, CF, and Bronchiectasis patients
There is a vaccination available
Who gets pneumonia from Moraxella catarrhalis:
Elderly individuals and COPD patients
Who gets primary pneumonia from Staph. aureus?
Hospital patients (nosocomial)
Who gets secondary pneumonia from Staph. aureus?
Children after measles
Adults after Influenza
(after a viral infection)
Who gets endocarditis from Staph. aureus?
(shoot up into a vein, bacteria travels to right heart, then can enter lungs)
What are two complications of pneumonia caused by Staph. aureus?
Who gets Klebsiella pneumonia?
How does pneumonia from Klebsiella present?
Thick gelatinous sputum (courant jelly sputum)
Extensive tissue destruction
Who gets pneumonia from Pseudomonas aeruginosa?
Hospitalized patients, burn victims, neutropenic patients, transplant patients
CF patients can get this in the community
How does pnuemonia from Pseudomonas aeruginosa present?
progressive and necrotizing
vasculitis and vascular spread
extensive tissue destruction and abscess formation
What is an upper respiratory tract infection from Legionella pmeumophilia called?
What is a pneumonia from Legionella pneumophilia called?
Where is Legionella pneumophilia found in the environment?
pools, shower heads, air conditioning units
ponds, stagnant water, etc.
Who was famously infected with Legionella pneumophilia?
Veterans at a conference (from WWI, WWII, and Spanish War)
Overweight, men in their 60s and older, who smoked
What does Atypical Community Acquired pneumonia present like?
fever, little or no sputum production
patchy or whole lung involvement, no consolidation
confined to alveolar septa (no exudate)
(can look like Lymphoid Interstitial Pneumonia, LIP)
What microbe is the most common cause of Atypical Community Acquired pneumonia?
What other bacteria cause Atypical Community Acquired pneumonia?
Chlamydia pneumoniae (mild form)
Chlamydia psittaci (psittacosis - fever, arthralgia, headache, from birds)
Coxiella burnetti (Q fever)
Francisella tularensis (tularemia - skin ulcers, from lagomorphs!)
Where is Atypical Community Acquired pneumonia most commonly found?
What viruses cause Atypical Community Acquired pneumonia?
RSV (respiratory syncytial virus)
How does Atypical Community Acquired pneumonia present?
respiratory distress is out of proportion to physical and radiographic findings
hard to culture, reticular opacities on CXR
variable, usually mild, fever, nonproductive cough
check for antibody titers
What is happening to the lung tissue n Atypical Community Acquired pneumonia?
Inflamed trachea and bronchi
Inflamed alveolar septa, edema, hyperemia, lymphocytes and plasma cells
Organisms attach to alveolar epithelial cells
Alveolar cells show inclusions, necrosis, multi-nucleation
Clear alveolar air sacs
What was the significant pandemic in 2009?
Swine Flu, H1N1, Influenza Type A
severe cases affected young and pregnant women most (elderly may have had previous antigen exposure and immunity)
What are the 3 typical microbes causing Hospital Acquired pneumonia?
Klebsiella, E. coli, Pseudomonas (all Gram -)
Describe aspiration pneumonia:
aspiration of foreign material (ex. gastric contents)
Abnormal gag or swallow reflex predisposes
Chemical and Bacterial
Alzheimer patients and Alcoholics (can be deadly)
Can lead to abscess formation
What is a lung abscess, briefly?
cavity in the lung secondary to suppurative destruction of lung tissue
full of neutrophils
What things can cause a lung abscess to form?
necrotizing bacterial pneumonia
secondary TB infection
septic emboli (IVDA)
hematogenous spread of bacteria
What microbe produces lung abscesses that can spread to the brain?
Nocardia (opportunistic fungus)
Which side of the lungs are abscesses more common on?
(right bronchus is straight, think of inhaling a peanut, it will go there, so will bacteria, gastric contents, etc.)
What are 4 complications of a lung abscess?
empyema, bronchopleural fistula, septicemia, amyloidosis (chronic inflammation)
How will a patient present if they have a lung abscess?
FOUL smelling sputum (cadaver breath)
productive cough, hemoptysis, malaise
How do you teat a lung abscess?
What are 2 other causes of a lung abscess?
Vasculitis (Churg Strauss and Wegner)
What is the other name for Wegener Granulomatosis? What is the little story?
Granulomatosis with Polyangiitis (GPA)
PolyAngie (Polyanna) went to Wegman's grocery store to get PR3 (ANCA-PR3)
What occurs in Wegener Granulomatosis?
Nodules -granulomas (palisaded, free giant cells)
Vasculitis (necrotizing, capillaritis)
How does Wegener present?
cough, hemoptysis, hoarseness, short of breath
CXR- nodules, infiltrates, cavitary lesions
(lungs and kidneys)
What is the other name for Churg Strauss?
Allergic Granulomatosis and Angiitis
What occurs in Chrug Strauss?
EOSINOPHIL (some micro-abscesses)
Granulomas (giant cells, palisaded)
"eosinphils CHewing on blood vessels"
What occurs in Lymphomatoid Granulomatosis?
Atypical lymphoid cells
Permeation of vessels (often not necrotic)
Necrosis (infarct like, palisaded rim)
What is Lymphomatoid Granulomatosis associated with?
EBV and it is classified as a B Cell Lymphoma
What causes chronic pneumonias?
TB and fungal infections
WHat is characteristic of chronic pneumonia in immunoCOMPETENT patients?
WHat is characteristic of chronic pneumonia in immunoCOMPROMISED patients?
What are three key epidemiological facts about TB?
Most prevalent in poverty and crowded areas
1.7 billion affected worldwide
Highly contagious and communicable
3 million deaths/year
What is the most important risk factor for TB?
What pneumoconiosis predisposes to TB infections?
distracts and occupies the macrophages
How is TB transmitted?
What is a TB infection?
exposure but not progressing to active tissue damage
What is active TB disease?
significant tissue damage
What type of HSR is TB?
involves T cells (that is why it is so prevalent in AIDS)
Where can TB found in an infection?
within the macrophages
Describe the Mantoux test:
2-4 weeks post infection
intra-cutaneous skin test causes palpable induration
10mm HCP (health care personnel)
Positive from exposure or from active disease
What will cause anergy, no reaction, to a PPD skin test?
sarcoidosis or overwhelming current TB infection
(T cells are being used up and won't cause skin induration to form)
Who gets Primary TB?
usually children or adolescents
cell mediated immunity confers resistance
results in hypersensitivity to TB antigens
What tissue findings are characteristic of a Primary TB infection?
Ghon focus (consolidation with necrotic center)
regional lymph nodes (also show caseation)
What is a Ranke complex?
Ghon complex undergoes fibrosis and then calcification and will be detectable on CXR (opaque)
Describe Mycobacterium tuberculosis:
acid fast bacilli (bind carbofuscin, stain red/pink)
mycolic acid cell wall (resists drying but not heat)
Describe Primary TB:
necrotizing granulomatous inflammation
aggreagates of epithelioid histiocytes and giant cells
What are 3 possible results of Primary TB?
hypersensitivity and increased resistance
scar with viable bacteria (can reactivate later)
progressive primary TB
What is Progressive Primary TB?
Apical lesion expands and erodes bronchus
Cough up necrotic center and get a cavitary lesion
Erodes blood vessel and causes hemoptysis
Spreads into lymphatics, drains into right heart, pulmonary veins, spreads throughout lung tissue
Miliary TB: systemic spread to any organ
Describe Secondary TB:
Reactivation of existing scar (with bacteria within)
Reinfection (exposed again after initial exposure facilitating immune response)
Localized at apex of lung
Cavitation erodes bronchus and vessels (hemoptysis)
Can also progress to miliary TB
What 3 MOT-TB (mycobacterium other than TB)?
Who gets MOT-TB infections?
little old frail white ladies with big puffy hair
(usually with underlying lung disease)
What happens in MOT-TB?
chronic localized infection, treated with antibiotics
the treatments don't seem to clear the organisms and eventually they develop more and more resistances, can be impossible to resolve and can be deadly
What are the 3 dimorphic fungi, and the 4th non-dimorphic?
Cryptosporidia (not dimorphic, always yeast)
small round yeast
southEASTERN US (Mississsippi River Valley)
bird and bat droppings
Anything TB does Histo can do better
Check transplant patients for Histo granulomas so that they don't reactivate
thick walled spheres, break and release endospores
southWESTERN US, in the dust
blasto, broad-based, budding
budding yeast, thick gelatinous capsule
soil or bird droppings (likes high N2 content)
localizes to lungs and disseminates to meninges
India Ink stain of CSF shows halo
What 2 organisms cause pneumonia in the Immunocompromised patients?
Cytomegalovirus HHV5 (neonates, AIDS, transplant)
What does CMV look like histologically?
Large cells, affects glands (latency)
Basophilic nuclear inclusions (Owl's Eyes)
Basophilic small cytoplasmic inclusions
What does PCP look like histologically (Pneumocystis jiroveci)
Foamy eosinophilic material (frothy, cotton candy)
Cup-shaped cysts (in alveoli air sacs)
(jiroveci-java-cup of java-cup shaped cysts)
Can look like Pulmonary Alveolar Proteinosis (PAP)
What organisms cause opportunistic fungal infections?
Who does Candida affect?
What does Candida look like?
budding yeast, pseudohyphae
produces a whitish membrane
What does Aspergillus look like?
septate, hyaline hyphae, acute angle branching
What three types of Aspergillus infection can occur?
Local (aspergilloma, fungal ball, old TB cavity)
Allergic (ABPA allergic bronchopulmonary aspergillosis, produces eosinophils and IgE)
Systemic (necrotizing, angio-invasive)
What does Zygomycetes look like?
Mucor, Rizopus, Absidia
non-septate lyaline hyphae
right angle branching
What do Zygomycetes like to do?
invade blood vessels
What causes Endogenous Lipid Pneumonia?
Obstruction of an airway or area of lung tissue
Accumulation of Foam Cells (Macrophages with cholesterol crystals)
Sometimes organizing exudate (fibrin) and lymphoid hyperplasia
What caused Severe Acute Respiratory Distress Syndrome (SARS)?
China, Hong Kong, Singapore, and Canada hit worst
8,000 people worldwide, only 8 people in US
What is the cause of cardiogenic pulmonary edema?
Left heart failure
What are some causes of non-cardiogenic pulmonary edema?
ARDS, high altitude, pulmonary embolism, neurogenic head trauma
What two other diseases can look like pulmonary edema histologically?
Pulmonary Alveolar Proteinosis (surfactant abnormality where glassy pink fluid collects in the alveolar space)
Pneumocystis Pneumonia (in HIV/AIDS patients, cup shaped cysts in alveoli air space filled with foamy pink exude)
What is the main cause of a pulmonary embolism?
from the deep leg veins
What are risk factors for pulmonary thromboembolism?
Immobility (airplane, bed rest, hospital)
Post Orthopedic Surgery
Trauma (burns, multiple fractures)
Congestive Heart Failure
Post pregnancy (hypercoagulable state)
Hypercoagulable state (Factor V Leiden, Protein C&S Def., Antithrombin 3 Def., Lupus Anti-coagulant)
What does the severity of the damage from a pulmonary embolism depend on?
size of the embolus (or number if showering)
cardiopulmonary status of the patient
What are the consequences of a pulmonary artery occlusion?
increased pulmonary pressure
vasospasm and release of TXA2 and 5HT
Ischemia of pulmonary parenchyma
high pressure in right heart
What can cause hypoxia in a pulmonary artery occlusion due to embolus?
Collapse of lung due to reduced surfactant in ischemic areas
Blood flow directed to normally hypoventilated areas
Widening of arterial-venous O2 gradient
Right to left shunt via patent foramen ovale (30%)
What is a saddle embolus?
a large embolus that lodges in both sides of the bifurcation of the pulmonary arteries
sudden death results from acute right heart failure
(no change in heart and lung tissue - no time)
What feeds the lungs with blood?
When does ischemic necrosis in the lung occur?
When there is concomitant CV compromise
wedge shaped, peripheral, pale
Describe the 3 types of pulmonary embolism:
Minor: 60-80% Asymptomatic
Major: 10-15% end artery occlusion + CV compromise, infarction, dyspnea
Massive: 5% sudden death, acute cor pulmonale
Pulmonary hypertension: <3% recurrent emboli
How much of the pulmonary circulation needs to be occluded for sudden death to occur?
large embolus or showering of many small emboli
Patients who have had a pulmonary embolism have what chance of having another?
30% chance of a second
What are the other non-thrombotic (less likely) emboli?
Air (diving), Fat (breaking bones), Amniotic fluid (Delivery), Bone marrow (CPR), Septic from IV drugs or infection
What defines pulmonary hypertension?
When the pressure on the pulmonary artery reaches > 1/4 of the systemic pressure
What causes pulmonary hypertension?
usually a decreased cross-sectional area of blood flow
Restrictive lung disease (interstitial)
Heart disease (mitral stenosis and L->R shunt)
Primary/idiopathic (sporadic or familial 6%)
What changes are seen in main elastic arteries in pulmonary hypertension?
What changes are seen in medium sized muscular arteries in pulmonary hypertension?
intimal cell proliferation
smooth muscle proliferation
What changes are seen in small arteries and arterioles in pulmonary hypertension?
reduplication of internal and external elastic lamina
What are plexiform lesions?
multiple lumina forming within small arteries at the branch point from a larger artery
proliferation of vasculature due to angio-proliferative growth factors released from damaged endothelium
lumen looks re-canalized in appearance
What factors mediate an increase in vasculature smooth muscle?
BMPR2 (bone morphogenic protein receptor 2)
Who does Primary pulmonary hypertension occur in?
How does Primary pulmonary hypertension present?
fatigue, syncope, short of breath, chest pain
death from right heart failure in 2-5 years
What does lung tissue look like in Primary pulmonary hypertension?
lung parenchyma looks normal
it is the vasculature that will show problems
What is given to treat Primary pulmonary hypertension?
vasodilators, anti-thrombotic agents, or lung transplant
If a patient presents with hemoptysis, anemia, and diffuse pulmonary infiltrates and these signs seem to be immune mediated, what type of disease might they have?
Diffuse Alveolar Hemorrhage Syndrome
What are 3 main Diffuse Pulmonary Hemorrhage Syndromes?
What are the 3 main features of Goodpasture's Syndrome?
Proliferative and Progressive glomerulonephritis
Hemorrhagic interstitial pneumonia
Antibodies to alpha 3 chain of collagen IV
What do the lungs look like in Goodpasture's?
heavy with red-brown consolidation (initially RBCs and later macrophages with hemosiderin)
Patchy necrosis of alveolar septum (where antibodies are being taken up by PMNs and Macs)
Septal thickening and Type II cells rounding up
What type of HSR is Goodpasture's
What does the deposition of antibodies look like in immunofluorescence?
continuous squiggly lines
linear deposition, antibodies are binding to alveolar septa BM and glomerular BM
(Ab-Ag complexes, type III, looks granular, clumpy)
Goodpasture's involves the lungs and the kidney and it is an immune reaction, what two things make it different from Wegener?
no granuloma formation in Goodpasture's
Ab is to alpha 3 chain of collagen IV (not ANCA PR3)
What are the treatments for Goodpasture's?
Plasmaphoresis to remove antibodies
Renal transplant in severe cases
When would you diagnose Idiopathic Pulmonary Hemosiderosis?
When a patient presented like Goodpasture's but no antibody could be found and there was no renal involvement (the lungs look the same)
Who is Idopathic Pulmonary Hemosiderosis usually found in?
What causes Idiopathic Pulmonary Hemosiderosis?
How is Idiopathic Pulmonary Hemosiderosis treated?
immunosuppression and steroids (even though no antibody has been seen)
If you find necrosis, neutrophil micro-abscesses, granulomas, and vasculitis in the lung tissue of a patient and there are renal complications as well, what antibody should you test for?
(anti-neutrophil cytoplasm antibody)
You patient presents with cough, hemoptysis, shortness of breath and hematuria, there is an increased antibody titer in the serum, you suspect Goodpasture's or Wegener. How would Wegener's appear on CXR?
Nodules, infiltrates (diffuse hazy opacity), cavitary lesions
What can be found in the upper respiratory tract and sinuses of Wegener patients?
How do the granulomas look in Wegener's?
necrotizing and not well formed
(TB is necrotizing but well formed, sarcoid is non necrotizing and very compact)
Who does Wegener's affect?
men and women of any age
What are the usual signs and symptoms presenting in Wegener's?
pneumonitis, nodules and lesions
mucosal ulcerations of the nasopharynx
rashes, myalgias, fever, neuritis, articular involvement
WHat is the progression of Wegener's if untreated?
80% mortality within 1 year (very deadly)
How is Wegener's treated?
steroids, anti-TNF, cyclophosphamide, Rituximab (immunosuppression)
What is the single most important cause of cancer death in developed countries?
The incidence of lung cancer in men is decreasing, what about in women?
increasing (oh no!)
At the time of diagnosis, what % of lung cancers already have metastases?
What is the 5-year survival for all stages of lung cancer?
Where are the likely places for lung cancer to metastasize to?
adrenal glands (50%) -> liver -> brain -> bones (vertebrae) -> kidney
Non-small cell lung cancer (NSCLC) makes up what %?
What types of lung cancer make up the NSCLC portion?
Squamous cell carcinoma 25-30%
Large cell carcinoma 10-12%
What are some gene mutations on NSCLC?
What do we distinguish between NSCLC and Small Cell lung cancer?
due to treatment options
NSCLC can be more easily surgically resected
Small Cell lung cancer responds best to chemo
What is the most common primary tumor?
Who gets adenocarcinoma?
women non-smokers, under 45 yrs.
What are the general characteristics of adenocarcinoma?
Peripherally located and Slow growing
Metastasize widely at early stage (but grow slow)
May be associated with a scar
Increase ALK levels
What is the precursor to adenocarcinoma?
Atypical Adenomatous Hyperplasia (AAH)
What is the progression of adenocarcinoma from AAH?
AAH -> adenocarcinoma in-situ -> minimally invasive adenocarcinoma -> invasive adenocarcinoma
What is another name for adenocarcinoma in-sit?
Bronchiolo-alveolar cell carcinoma (BAC)
What does adenocarcinoma in-situ look like histlogically?
Lepidic growth (butterflies sitting on a fence)
Not invaded the basement membrane
Signet ring cells full of mucin
What classifies minimmaly invasive adenocarcinoma?
>3mm but <5mm nodules
What classifies invasive adenocarcinoma?
papillary (central fibrovascular core, finger like shape)
solid (solid sheets)
micropapillary (poor prognosis, chemo)
What does adenocarcinoma look like on CXR?
Ground glass opacity
Along alveolar septa, widening them
(treat with anti-biotics and it doesn't go away)
What stain is used to identify adenocarcinoma?
PAS stain will show mucin production from these tumors (looks pink), they are from glandular origin
What immunohistochemical markers determine adenocarcinoma?
What are some gene mutation in adenocarcinoma?
EGFR and Kras
(will determine treatment options)
Who gets Squamous Cell Carcinoma?
men who smoke
What are the characteristics of squamous cell carcinoma?
Spreads to hilar lymph nodes first
Extrathoracic spread occurs later than other types
Can have obstruction, atelectasis, infection
What are the steps in the development of squamous cell carcinoma?
smoking -> chronic bronchitis -> squamous cell metaplasia -> squamous cell dysplasia -> squamous cell carcinoma in-situ -> invasive squamous cell carcinoma
What is distinctive in squamous cell carcinoma?
cavitary lesions with central necrosis
Keratin pearls that look whorled
Intracellular bridges that have a prickled appearance
What immunohistochemical markers determine squamous cell carcinoma?
What are the characteristics of large cell carcinoma?
Poor prognosis, early metastases
undifferentiated epithelium, lots of cytoplasm
lacks features of small cell
no gland differentiation
no squamous differentiation
What are the two types of large cell carcinoma?
Type 1 - undifferentiated
Type 2 - neuroendocrine
What are the markers for Type 1 and Type 2 large cell carcinoma?
Type 1 - keratin +
Type 2 - chromogranin, synaptophysin, D56
Who gets small cell carcinoma?
(99% of the time there is smoking history)
What are the characteristics of small cell carcinoma?
early metastases to mediastinal lymph nodes
frequent vascular invasion (vascular & lymph spread)
usually cannot be surgically resected
responds well to chemo/radiation
causes paraneoplastic syndromes
What do the cells look like in small cell carcinoma?
round with little cytoplasm
finely granular chromatin - Salt and Pepper nucleus
fragile with crush artifacts
nuclear molding (don't hold their own shape)
What immunohistochemical markers determine small cell carcinoma?
(it is a neuroendocrine tumor)
What are some of the para-neoplastic syndromes associated with small cell lung cancer?
What are some gene mutations on small cell carcinoma?
myc amplification (growth pathway signaling)
p53 and pRb
What are a few quick facts about smoking and lung cancer?
heavy smokers 60X risk to non-smokers
15 years after quitting still not at baseline risk
females more susceptible to cancer than males
passive smoking is 2X risk
only 11% of heavy smokers develop lung cancer
asbestos + smoking is 55X risk
What is difficult about peripheral tumors?
they may be clinically silent and hard to detect early
What are some complications that arise due to centrally located tumors?
obstruction of an airway
infection (pneumonia, abscess, bronchiectasis)
How does lung cancer present clinically?
cough, weight loss, hemoptysis, dyspnea, clubbing of the fingers (osteoarthropathy), hoarseness, chest pain, preicardial or pleural effusion, atelectasis, pneumonitis
What are 4 syndromes related to lung cancer?
Superior Vena Cava Synd.
Describe SVC Syndrome:
Patients have a congested head and neck due to obstruction of the SVC
Describe Horner Syndrome:
Compresion of the cervical sympathetic plexus
ptosis, meiosis, anhydrosis
Describe Pancoast Syndrome:
due to an apical lung lesion (T1&T2 destruction)
wasting in hand muscles and arm pain (ulnar nerve)
compression of blood vessels and edema
hoarseness due to recurrent laryngeal nerve paralysis
dysphagia due to esophageal compression
chylothorax from thoracic duct obstruction
What are the various Para-neoplastic Syndromes?
Hypercalcemia from increased PTH (in Squamous Cell)
Cushing's Syndrome (increased ACTH)
Syndrome of Inappropriate ADH (hyponatremia)
What is involved in Cushing's Syndrome?
increased ACTH, bilateral adrenal hyperplasia, moon face, buffalo hump, weight gain, sweating, striations on the skin, telangiectasia, baldness, insomnia
Patients who have adenocarcinoma with mutations in the EGFR gene respond to what treatment?
Tyrosine Kinase Inhibitors (Gefitinib and Erlotinib)
(and they respond to pemetrexed)
In what patients is Bevacizumab contraindicated?
Squamous cell carcinoma patients
Causes hemorrhage, life threatening bleeds
When would a patient with adenocarcinoma respond poorly to tyrosine kinase inhibitors?
if they had a Kras mutation
(the two mutations are mutually exclusive, will only have one or the other)
What is used to treat patients with a Kras mutation and how does it work?
inhibits the EMNL4/ALK fusion protein (which is found in 45% of NSCLC)
What is diffuse pulmonary neuroendocrine cell hyperplasia (DIPNEC) related to?
Who gets carcinoid tumors?
women around 40 yrs.
What cells do carcinoid tumors arise from?
(typical of all neuroendocrine tumors really)
What determines the atypical variant of carcinoid tumors?
high mitotic count (>2/10hpf) and necrosis
What are the characteristics of carcinoid tumors?
More "well behaved" but still malignant, localized but can still metastasize
What does a carcinoid tumor look like?
cells are nested together, uniformly rounded
salt & pepper nuclei
rare mitosis, no pleomorphism
How will a carcinoid tumor present?
Obstruction, cough, hemoptysis
Carcinoid Syndrome in 1%
What is Carcinoid Syndrome?
Neuropeptides secreted into blood stream (5HT and histamine)
causes flushing, vasomotor disturbances, cyanosis
GI hypermotility, diarrhea, cramps, vomiting
What is a hamartoma?
benign tumor of mixed normal tissue
in correct location but disorganized
cartilage, epithelium, smooth muscle, CT all mixed
incidental finding on CXR