Pulm 2 Flashcards
What is honeycomb lung?
End stage lung -final result of many interstitial lung diseases
Severe fibrosis with architectural remodeling resulting in large arispaces with thick fibrous walls
What is this?
Honeycomb lung- end stage lung
What is this?
HOneycomb lung
What are common featurs of interstitial lung diseases?
Decreased compliance
Decreased lung volumes
Impaired diffusion
Devlopment of pulm HTN
How does fibrosis happen?
Abnromal repair with replacement by dense connective tissue and loss of normal architecture
Pathogenesis is poorly udnerstood, but linked to inflammation and abnormal wound healing
What is the interstitium of the lung?
Basement membrane of endothelial and epithelial cells, fibroblasts, collagen fibers, and elastic tissue
What do we see here?
Interstitial lung disease
Normal is :
what is Usual interstitial pneumonia (UIP)?
Age = 50+
Insiduous onset with exertional dyspnea and chronic evolution
Complications include pulm HTN, cor pulmonale and cardiac failure
Assoc. with collagen vascular disorder or autoimmune, but most ar idiopathic
What is Idiopathic pulmonary fibrosis (IPF)?
UIP pattern on histology plus idiopathic disease clinically
UIP = Usual interstitial pnuemonia
What do you see on hisotlogy in UIP?
PATCHY fibrosis, most pronounced beneath plura next to interlobular septa
Fibrosis has TEMPORAL HETEROGENEITY - not all same age -> Fibroblast focus = region on loose blue-gray connective tissue adjacent to an area of dense collagenous scar (new and old fibrosis next to each other)
What is a fibroblast focus?
Region of loose blue-gray connective tissue (new fibrosis) next to an area of dense collagenous scar (old fibrosis)
What do we see here?
Patchy fibrosis with subpleural predominance
UIP
What do we see here?
Patchy fibrosis
Severe alternates with spared lung
UIP
What do we see here?
Fibroblast focus - odl and new fibrosis
UIP
How do you treat UIP?
Steroids provide minimal benefit
3 years or less survival mean
Transplant may be an option
What is Non-specific Interstitial Pneumonia (NSIP)?
Similar to UIP clinically, but seen in younger patients
Improved prognosis over UIP especially at 5 years
Cellular has better prognosis than fibrosing subtype
Responds better to steroids
What do we see in NSIP on histology?
Cellular: diffuse chronic inflammatory cell infiltrates without significant alveolar expansion; no fibrosis
Fibrosing: diffuse interstitial fibrosis with uniform appearance; fibrosis is all same age (temporally uniform); lung architecture preserved
What is this?
Cellular NSIP - uniform involvement of lung by chronic interstitial inflammation
What is this?
Fibrosing NSIP - uniform involvement of lung by fibrosis of the same age
What is lymphocitic interstitial pneumonia (LIP)?
Rare- seen in patients with sjogren’s syndrome and HIV
Rarely idiopathic
Presents as cough/dyspnea
Radiology classically shows diffuse ground glass changes with cysts
What do you see in microscopy on LIP?
Small mature lymphocytes with variable numbers ofplasma cells expandign the alveolar septa
What do we see here?
LIP
What is sarcoidosis??
Multisystemic disease of unknown origin with lung involvement in 90% of cases
Classic: Interstitial/nodular lung infiltrates and bilateral hilar adenopathy
20-40 years; Females, 90% black
Elevated serum ACE
Most people recover
What do you see clinically in sarcoidosis?
Lungs: either no gross lesion or 1-2 cm nodules, often in bronhial submucosa
LN: hilar or mediastinal lymph nodes
Liver/spleen: microscopic involvement
Bone: xray changes in 20% in small bones
Skin: 30-50% involvement
Eye: iritis or iridocyclitis in 20-50%
How does sarcoidosis appear morphologically?
NON-NECROTIZING epithelioid granulomas
Tightly packed epithelioid cells, giant cells, and T cells adjacent to bronchioles aroudn broncovascular bundle
Diffuse interstitial fibrosis in small number of cases
What do we see here?
Sarcoidosis
What do we see here?
Non-caseating granuloma
Sarcoidosis
How do you diagnose sarcoidosis?
Diagnosis of exclusion as other things can casue it (infeciton, hypersensitivity pneumonitis)
What is hypersensitivity pneumonitits (extrinsic allergic alveolitis)?
Inhalation of organic antigen
Acute: within hours of exposure -not well described
Chronic: extended exposure, may be progressive with fibrosis (type 3 and 4 hypersensitivity combination)
What is the inciting event in hypersensitivity pneumonitis?
Typically due to exposure to thermophillic bacteria or fungi
What is the classic triad of hypersensitivity pneumonitis?
Chronic bronchiolitis/interstitial pneumonia
Poorly formed/vague granulomata
Organizing pneumonia
Long standing chronic disease may evolve into diffuse fibrosis
What do we see here?
Bronchiocentric pattern of inflammation in hypersensitivity pneumonitis
What do we see here?
Hypersensitivity pneumonitis
Peribronchiolar inflammation with airway remodeling
What do we see here?
Poorly formed granuloma
Hypersensitivtiy Pneumonitis
What is respiratory bronchiolitis and respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)?
RB is accumulation of macrophages in smokers with granular brown pigment in small airways
RB-ILD is RB on biopsy plus clinical symptoms of interstitial lung disease (and no other findings)
What do we see here?
Respiratory bronchiolitis
What is desquamative interstitial pneumonia (DIP)?
Similar to RB-ILD but disease is more diffuse and with more severe symptoms
Adults typically with insiduous shortness of breath
Exclusively seen in smokers
X-ray shows bilateral lower lobe, gorudn glass infiltrates
Tx with steroids and smoking cessation
What do you see microscopically in DIP?
Diffuse collections of intraalveolar macrophages containing finely granular brown pigment
Minimal involvement of alveolar septa; no significant firosis
What do we see here?
DIP
Desquamative interstitial pneumnia
What do we see here?
Smoker’s macrophages with finely granular brown pigment
Seen in Desquamative interstitail Pneumonia (DIP)
What is langerhans cell histiocytosis?
Seen exclusively in cigarette smokers (males)
Bronchiolocentric fibrosis with stellate scar formation
Variable numbers of langerhans cells, eosinophils
S-100, CD1a positive
What do we see here?
Stellate airway centerd fibrosis of langerhans cell histiocytosis
What do we see here?
Langerhans cells, eosinophils, and pigmented macorphages of langerhans cell histiocytosis
What do we see here?
Birbeck graule characteristic of histiocytes
What is a ferruginous body?
General term referring to any inorganic substance with a coating of iron and protein - graphite, ceramic, iron, etc
What is an asbestos body?
Ferruginous body formed on an asbestos fiber - characterized by clear internal core and beaded ferruginous coating
What are manifestations of asbestos disease?
Pleural fibrosis and/or pleural plaques (bilateral, calcified)
Pulmonary parenchymal fibrosis (asbestosis) leading to end stage fibrosis (honeycomb lung)
Malignancies (lung carcinoma, mesothelioma)
What are pleural plaques?
Well circumscribed plaques of desne collagen, often with calcium, on parietal pleura and dome of diaphragm, doesn’t contain asbestos body, but rare if no asbestos history
May induce pleural effusion, no symptomatology typically
What do we see here?
Benign plaques - parietal and diaphragmatic pleura
What is asbestosis?
Diffuse interstitial fibrosis secondary to asbestos exposure (heavy)
Initial injury at bifurcations of small airway and ducts
Fibrosis begins aroudn respiratory bronchioles and alveolar ducts, extending distally, causing honeycomb lung
Begins in lower lubs and subleurally and proresses upwards
What do we see here?
Honeycomb on left, normal on right
Asbestosis
What do we see here/
Asbestosis - mimics UIP
What do we see here?
Giant cell reaction to asbestos bodies
What do we see here?
Asbestos bodies
What is silicosis?
Chronic occupational lung disease casued by exposure to free silica dust
Seen in miners, glass manufacturers, sand blasters, and stone cutters
INgestion of silica by alveolar macrophages -> damage initiates inflammatory response
Marked by silicotic nodules that enlarge and obstruct airways and blood vessels
Increased susceptibility to TB: Silicotuberculosis
How does silicosis appear grossly?
Early, tiny, discrete pale to black nodules in upper lungs
NOdules have stellate shape at edges
Fibrosis present at hilar nodes and pleura - eggshell calcificaiton
What do we see here?
Silicosis
How does silicosis appear microscopically?
Early - small nodules of fibroblastas and histiocytes with abudnant cilia
Onion-skin fibrosis typically
Become more hyalinized over time with proressive massive fibrosis
Later is hyalinized and condensed collagene needle-like spicules with pointed ends
What do we see here?
Subpleural silicotic nodule
What do we see here?
Silicotic nodule
What do we see here?
Silicotic nodule with lamellar fibrosis
What dow e see here?
Silica under polarized light
What is coal worker’s pneumoconiosis?
Coal macules and coal nodules scattered throughout lung
Seen in upper lobe and upper lower lobe, near respiratory bronchioles
Minimal symptoms, but 10% develop progressive massive fibrosis
What is progressive massive fibrosis?
Complicated coal worker’s pneumoconiosis -> intensely blackened scars contianing dense collagen and pigment; may be necrotic
What is caplan syndrome?
Rheumatoid arthritis and pneumoconicosis cause rapidly developing nodular pulmonary lesions identical to rheumatoid nodules typically seen in soft tissue
What do we see here?
Simple coal workers pneumonconiosis
What do we see herE?
Simple coal worker’s pneumonconiosis
What do we see here?
Black lung
Progressive massive coal worker’s pneumoconiosis
What do we see here?
Massive progressive coal worker’s pneumoconiosis
What is IIP?
Idiopathic interstitial pneumonias
Acute, chronic or sub-actue
Respiratory symptoms are non-specific
RESTRICTIVE (Decreased FVC< TLC, preserved FEV1/FVC ratio, decreased DLCO, and incerased A-a gradient)
What are fibrotic changes on chest x-ray in interstitial lung disease?
Traction bronchiectasis
Reticular densities
Honeycombing
Cysts
What do we see here?
Traction bronchiectasis
What do we see here?
Reticular abnormalities
What do we see here?
Honeycombing and Cysts
What are inflammatory radiographic changes you see in interstitial lugn disease?
Ground glass opacity
Consolidation
What do we see here?
Ground glass opacity of inflammatory interstitial lung disease
What do we see ehre?
Consolidation of inflammatory interstitial lung disease
What is IPF?
Idiopathic pulmonary fibrosis
Usual interstitial pneumonia is the histoopathology pattern
Most common of the IIPs
Most deadly (90% mortality)
Who gets IPF?
Older people
Males more than females
What are salient clinical features of IPF?
Subacute or chronic
Insidious onset of dyspnea
Cough
Rales
Clubbing
Restrictive PFTs (TLC, FVC)
Impaired gas exchagne (DLCO, A-a gradient)
There is no diagnostic blood test
What do you suspect here?
IPF - idiopathic pulmonary fibrosis
Basal, peripheral, subpleural
What do we see here?
IPF on the right, normal on left
What is the prognosis for IPF?
Very bad
Things that are worse:
Pulmonary HTN
Low DLCO
Decrease PFT’s over 6 months
Desaturation to SpO2 < 88%
Fibroblast foci on surgical lung biopsy
How do you treat IPF?
Nothign works
Lung transplant is only good option
Which IIP has the best prognosis?
COP (Cryptogenic Organizing Pneumonia)
What does Interstitial Lung Disease indicate about the prognosis for a patient with a connective tissue disorder?
Worsens prognosis
What is the interstitial lung disease seen in connective tissue diseases?
Nonspecific interstitial pneumonia
Specific histologic pattern (uniform)
Young patients, associated with Systemic scleroderma, Dermatomyosytis, polymyositis
Good response to therapy: fair prognosis
Who gets sarcoidosis?
20-40 years old; (second peak in Japan and Scandanavia in women > 50)
Females:Males 2:1
More prevalent in blacks (more common, and present more severe, and with extrapulmonary disease)
What is the proposed mechanism of sarcoidosis?
genetically predisposition
Cell mediated immune response to one or more unidentified antigens
Hallmark of sarcoidosis = epithelioid granulomas
CD4 driven process
What cell type drives the disease in sarcoidosis?
CD4 T cells
What is needed in order to diagnose sarcoidosis
BIOPSY
What is Lofgrens Syndrome?
Sarcoidosis syndrome
Erythema nodosum, hilar adenopathy, uveitis
Patients are symptomatic from erythea nodosum and arthralgias, seek medical attention -> good prognossis
BAL shows acticated CD4 lymphocytes
Bizarre, explosive manifestation; resolves
What ist he relationship between the respiratory tract and sarcoidosis?
Occurs at some time in essentially all patients (90% is sole manifestation)
Dyspnea, cough, chest pain in many; hyperreactivity in 20%, obstructive disease in up to 30%
Interstitial lung disorder involving alveoli, blood vessels, bronchioles (T cell alveolitis)
Bronchoscopic lung biopsy diagnostic in > 80% of patients
What do you see here?
Stage 1 sarcoidosis
bilateral hilar adenopathy
seen in 50% of patients; no respiratory symptoms
60-80% have spontaneous remission
What do you see here?
Stage 2 sarcoidosis
Lymph node involvement + interstitial infiltrates
In 25% of patients
Have symptoms of fever, weight loss, dyspnea
50-60% have spontaneous remission
What do we see here?
Stage 3 sarcoidosis
15% of patients
Significant respiratory impairment
<30% have spontaneous remission
Non-productive cough; restrictive disease
What do we see here?
Stage 4 sarcoidosis
5% of patients
Chronic respiratory impairment
High mortality rate
Restrictive lung disease, may develop pulmonary HTN, may become colonized with aspergillus
Where in the lung lobes do you typically see infiltartion in sarcoidosis?
Upper lung zones
What do you see on pulmonary funciton tests in sarcoidosis?
Restriciton more common
Gas transfer defect is likely
OBstruction may be present with or without bronchodilator response (endobronchial disease and/or reactive airway)
How is the lymphoid system involved in sarcoidosis?
1/3 have palpable lymph nodes (Cervical, axillary, epitrochlear, inguinal)
Discrete, movable, nontender
Non ulcerative
Extrapulmonary nodes more frequently seen in blacks
What is the relationship between sarcoidosis and the larynx?
1-5% of patinets
Hoarseness, dyspnea, stridor
Epiglottos most commonly involved
Localized edmea and erythema with punctate nodules and mass lesions
What is the relationship between sarcoidosis and the eye?
1/3 of patinets
Uveitis, chorioretinitis, vitreous opacities, keratoconjunctivitis
lacrimal gland enlargement
MOre frequenlty seen in women
What is the relationship between the heart and sarcoidosis?
Ventricular arrhytmias
Sudden death in young males
Heart block, supraventricular arrhytias and CHF/cardiomyopathy
EKG recommended
What ist he relationship between sarcoidosis and the skin?
21% of patients
Erythema nodosum is most comon
Maculopapular eruptions, skin plaques, alopecia, subcutaneous nodules
Lupus pernio characteristic - most common in black women, associated with bone scysts and pulmonary fibrosis
What do you see her?
Erythema nodosum
What is the relationship between sarcoidosis and MSK?
Arthropathy in 25-40%
Arthralgias may occur without radiographic changes, effusions, or erythema
BOne involvement uncommon
Muscle involvment common ((weakness, aches)
What is neruosarcoidosis?
CNS involvemnet in sarcoidosis (less than 10%)
Prediliciton for base of the braine (CN inovlvement (Facial palsy, optic neuropathy), hypthalamic and pituitary)
More common in women
Space occupying lesions
What are endocrine manifestations of sarcoidosis?
Hypercalcemia in 2-10% (more common in men)
Hypercalcuria in 6-30%
Due to dysregulated production of 1,25-dihydroxyvitamin D3 (calcitriol) by activated macrophages and granulomas
Can cause nephrocalcinosis, renal stones, and renal failure
What is the relationship between sarcoidosis and liver/spleen/kidney?
granulomas found in 50-80% of liver biopsy specimens
hepatomegaly in <20%
abnormla LFTs common
SPlenomegaly
Interstitial nephritis is rare
How do you work up a diagnosis of sarcoidosis?
Histological confirmation
Assess extent and severity of organ ivolvemnt
Asses likelihood of stability or progression
Determine if therapy will be of benefit
Diagnosis is of exclusion (clinical picture + histology + not something else)
How do you choose a biopsy site for sarcoidosis?
Transbronchial lung biopsy is recommended (low risk)
Lymph nodes when palpable
What are prognostic factosr that indicate a likelihood of spontaneous remission of sarcodiosis?
Erythema nodosum and acute inflammatory manifestations
What are adverse prognostic factors for sarcoidosis?
Lupus pernio
Chronic uveitis
Age > 40 at onset
Chronic hypercalcemia
Nephrocalcinosis
Black race
Cystic bone lesions
Neurosarcoidosis
Cardiac sarcoidosis
How do you treat sarcoidosis?
No treatment
If any, corticosteroids
What is on the differential of a sarcoidosis diagnosis?
What is a difference bwetween water soluble vs insoluble respiratory irritants?
Soluble : immediate effect on Upper respiratory tract and bronchi
INsoluble: delayed effect on alveoli to cause pulmonary edema
What pattern of fibrosis do you see in with coal dust in the lungs?
Progressive massive fibrosis
What pattern of fibrosis do you see with silica dust in the lugns?
Nodular fiboriss (silicosis)
Progressive massive fibrosis
Can get TB as a complication
What pattern of fibrosis do you see wiht asbestos dust in the lungs?
Diffuse fibrosis (asbestosis)
As a complicaiton, you can get lung cancer
What is pneumoconiosis?
Pulmonary disease caused by the inhalation of dusts
Classfiied by type of dust (inorganic, organic), and/or type of pathology (fibrosis, granulomas)
What does inorganic dust cause in the lung?
Pnemoconiosis
Dose related
Predictable response
Acts like direct toxicant
What are features of inorganic dust-related lung disease (pneumoconiosis)?
Dose related
Predictable response
Acts like direct toxicant
What is the result of organic particle-related lung disease?
Hyeprsensitivity pneumonitis
Idiosyncratic
prior exposure
Acts like antigen
What is pneumoconiosis: silicosis?
Results from inhalation of silica; seen in miners, sand-blasters, metal polishing, etc; found in quartz
ingestion by alveolar macrophage; damages macrophage; autolysis of cells and reingestion of particel; disruption of immune cells = susceptibility to TB; releases fibrogenic mediateos and forms silicotic nodules
What do we see here?
Silicosis: silicotic nodule consisting of hyaline collagine arranged in whorled pattern
Whgat are clinical syndromes that can result from silicosis?
Simple nodular silicosis
Progressive massive fibrosis
Silico-tuberculosis
Where do the nodules of silicosis tend to migrate to?
Upper lobes
Hilar nodes (upper)
What is progressive massive fibrosis in silicosis?
Cavitating PMF, moves upwards in lobes
What arde diseases seen in coal miners?
Anthracosis
Simple coal workers pneumoconicosis
Complicated coal workers pneumoconicosis (progressive massive fibrosis)
What is anthracosis?
Asymptomatic carbon dust in lugns
Seen in urban dwellers, coal miners, smokers
Hardly a disease
What od we see here?
ANthracosis - harmless deposition seen in urban dwellers, smokers
What is simple CWP?
Greater exposure to coal
NO pulmonary dysfunction, except may be associated with emphysema
Macules aggregates of pigment + macrophages
NOdules may be larger
Contain collagen
WHat are three diseases seen with asbestos?
Pleural plaque
Interstitial lung disease (asbestosis)
Malignancy (lung carcinoma, pleural mesothelioma, carcinoomas elswehre in respiratory tract)
What is a pleural plaque?
acellular plaque on parietal pleura
NOt assoicated with pulmonary dysfunction
Good indicator of asbestos exposure
Occasional finding at autopsy
Whgat is this?
Asbestos plerual plaque
What is asbestosis??
Diffuse interstitial lugn disease resulting from inhalation of asbestos
Disffuse interstitial fibrosis and asbestos bodies
Progressive respiratory impairment
Lower lobes, shaggy heart
What is this?
Asbestosis
What are the treatments available for and the prognosis of inorganic dust disease (pneumoconicosis)?
NO treatment
Early recognition to stop exposure
May still progress after exposrue stops
What is RADS (reactive ariways dysfucntion syndrome)?
Development of respiratory symptoms in minutes or hours after single accidental inhalation of high concentration of irritant, gas, aerosol, or particles
FOllowed by asthma-like symptoms and airway hyperresponsiveness for prolonged period
What is byssinosis?
Breathing in cotton dust or dusts from other vegetable fibers such as flax, hemp, or sisal while at work
When sensitized can have asthma-ilke condition after beign exposed
WHat is unique about hte structure of pulmonary vessels?
Thin walled vessels, compliant, distensible
Can handle entire cardiac output wihtout high pressures
What are features of the pulmonary circulation (pressure, resistance)?
Low pressure, low resistance
What are systolic and diastolic pulmonary artery pressures?
25/10
How do you measure mean pulmonary artery pressure and mean left atrial pressure?
Swan Ganz Catheter
What is the pulmonary vascular response to exercise?
Increased cardiac output results in a decrease in mean pulmonary vascular resistance
Recruits new vessels, distends previously perfused vessels
High capacity, high compliance, low pressure, low resistnace
Which zone of hte lung undergoes most changes during exercise?
Zone 1 -> increased blood flow; V/Q ratio nears 1 (rather htan 3.3) in zone 1
What is the pulmonary vascular response to hypoxia?
Vasoconstriciton in response to alveolar PO2 of 60-70 mmHg
Protective mechanism: decreases perfusion to poorly ventilated areas in order to reduce the V/Q mismatch
don’t see global abnormalities really
How does hypoxic pulmonary vasoconstriction occur?
Hypoxia inhibits pulmonary artery smooth muscle K+ channel
Ca++ influx and results in smooht muscle contraction
Hypoxia causes decreased NO production
Effects of pH are additive (acidemia causes vasoconstriction too)
What are normal mediators of pulmonary vascular tone?
Endothelin
Nitric oxide
Arachidonic Acid metabolism products (PGI2 and TXA2)
What are the effects of the arachadonic acid metabolism products on pulmonary vascular tone?
Thromboxane = constriction
Prostacyclin = dilation
What defines pulmonary hypertension??
mPAP > 25 mmHg at rest and > 30 mmHg during exercise
What are the three factors that lead to pulmonary hypertnesion/
Endothelial injury leading to intimal hyperplasia
Abnormal flos (in situ thrombosis)
Smooth muscle hypertrophy
All lead to vbvascular remodeling
What is the clinical progression of pulmonary hypertension?
What is cor pulmonale?
Right sided heart failure
ENlargement of the right ventricle due to high BP in the lungs, typicalyl caused by chronic lung disease
What are some underlyign causes of pulmonary hypertension?
Venous congestion
Destruction of microvasculature
Increased blood flow
Hereditary
Mechanical arterilal obstruciton
Hypoxic vasoconstriciton
Obliteration of vessels
Idiopathic
What do you see in idiopathic pulmonary hypertension?
Medial hypertrophy
INtimal hyperplasia
Plexiform lesions
Neo-muscularization
In situ thrombosis
Women more than men
Age 20-45 years
Median survival is < 3 years
Requires aggressive therapy with multiple drugs
Who gets idiopathic pulm HTN?
Women
Age 20-45 years
What gene is involved in a heritable form of pulm HTN?
BMPR2 (bone morphogneic receptor type 2)
Loss of inhibitory control
Cuases dysegulated endothelial repair, thickening, smooth muscle hypertrophy
What are some causes of group 1 pulm HTN?
Idiopathic
Genetic
Connective tissue diseases
HIV
Portopulmonary
Schistosomiasis (most common in developing countries)
Hemoglobinopathy
Drugs/toxins (cocaine, methamphetamine, fen-phen)
What is gropu 2 pulm HTN?
Caused by left sided heart disease’
Increased back presure from left atrium
Mitral stenosis and left ventricular systolic failure
Treat underlying cardiac disease
What is Group 3 pulm HTN?
Hypoxia associated conditions
INterstitial lugn disease, COPD, obstructive sleep apnea, chest wall disorders, obesity
Hypoxic pulm vasoconstriction
Destruciton of alveolar surface area due to scarring/emphysema
RV failure can lead to cor pulmonale
NEeds treatment of underlying disease and correciotn of hypoxia
What is group 4 pulm HTN?
Chronic thromboembolic
Multiple and recurrent PEs
Occlusion of blodo vessels wtih clots gives rise to increasing PVR
Needs anticoagulation and surgery (thromboendarterectomy)
What are clinical features of pulmonary HTN?
Exertional dyspnea
Exertional fatiuge
Chest pain, palpitations, light headedness
Syncope
Lower extremity edema
Raynaud’s PHenomenon
What can you see on physical exam in a patient with pulmonary HTN?
Lower extremity edema, JVD, hepatomegaly, ascites
Loud P2, RV heave
Right sided S3 (mid diastolic)
Right sided S4 (pre systolic)
Systolic murmor of tricuspid regurg
Graham Steell murmor of pulmonary insufficiency
What diagnostic tests do you order when you suspect pulmonary HTN?
Chest Xray
See hilar prominaence
Pruning of vessels
Underlying COPD, ILD
What do we see here?
CXR of Pulmonary HTN
What is the best diagnosit test for gropu 2 pulm HTN?
Echo - non-invasive heart ultrasound to check heart function (group 2 is caridac related)
What do we see here?
Echo in pulm HTN
WHat is the gold standadr for diagnosis of pulmonary HTN?
Right heart cath (swan ganz)
Why do you order a ventilation/perfusion scan when you suspect pulmonary HTN?
To check for thromboembolic causes -> CURABLE
How do you treat pulmonary HTN?
Essentially counter the effect of vasoconstrictors in the pulmonary vasculature
Blocking endothelin receptor (endothelin receptor antagonist)
Augment nitric oxide
Augment prostacyclin (PGI2) - analogs
What are the components of Virchow’s Triad?
Stasis
Venous injury
Hypercoagulability
What is a mnemonic to remember the risk factors for thromboembolism?
SIT CALM
Surgery
Immobilizaiton
Trauma/Thrombophilia
CHF
Age
“Lines” -catheters
Malignancy
What is the most common genetic risk factor for thrombophilia?
Factor V Leiden Mutation
What is the relationship between malignancy and thromboembolisms?
Pro-coagulant effects of tumor; immobility, presence of catheters
What is the relationship between DVT and pulmonary embolism?
79% of PE patients have DVT
50% of patients with DVT get PEs
Femoral vein is common
What pathophysiologic defect occurs in PEs?
Dead spacing
Why is there hypoxemia in PEs?
Chemical mediators released by thrombi (serotonin) can cause small airway constriction (low V/Q - like a shunt)
Surfactant produciton is impaired (collapse of alveoli - atelectasis -> low V/Q units)
Impaired cardiac output -> increased O2 extraction -> decreased venous SpO2
What are typical symptoms of PE?
Dyspnea at rest or exertion
Pleuritic pain
Cough
Orthopnea
Calf or thigh pain/swelling
Wheezing
What are signs on PE for PE?
Tachycardia
Tachypnea
Hypotension (if massive)
JVP
Decreased breath sounds, dullness, sometimes wheezing
Extremities for DVT, Homan’s sign
What are diagnostic modalities for PE?
ABGs
ECG
D-Dimer
Imaging
What do you see on arterial blood gases in PEs?
Respiratory alkalosis (Tachypnea)
A-a gradient (hypoxemia in low V/Q units)
Metabolic acidosis (lactic acidosis) if massive PE
How can an EKG help diagnose PE?
Non-specific ST/T changes
Sinus tachycardia
Maybe a RBBB or RAD with massive PE
S1Q3T3
What is the usefulness of d-dimer in PE diagnosis?
Very sensitive (good negative predictive value) - Normal rules out PE
Not very specific - can be anything else
What can you find on CXR in a patient with PE?
Normal CXR is classic
Can see hampton’s hump, enlarged pulm artery, westermark’s sign, or plerual effusions
How does an ultrasound help diagnose PE?
Can identify a DVT if it s there
How can a V/Q scan help diagnose PE?
Normal VQ scan effectively rules out PE - > negative predictive value is almost 100%
What are pros and cons of CT angiogram for PE diagnosis?
Very good image of vasculature and parenchyma
Cons: IV contrast exposes patients to radiation and also is nephrotoxic
What lesion do you characteristically see in primary pulmonary hypertension
Plexiform lesion
When do you see plexiform lesions?
Primary pulmonary hypertension, not in secondary
What is a plexiform lesion?
Dilated segment of artery consisting of numerous slits like vascular channels
Primary Pulmonary HTN
What pulmonary signs do you see pathologically in Wegener’s Granulomatosis?
Irregular areas of necrosis
Vasculitis
What is Churg-Strauss syndrome?
Triad of asthma, eosinophilia, and vasculitis
Male=Female; ~50 year olds
Neuropathy, cardiac, lung, sinonasal involvement; Renal involvement NOT common
Lung Xray with multifocal infiltrates (change over time)
What do you see on lung pathology in Churg-Strauss?
Histology: asthmatic bronchitis, eosinophilic pneumonia, extravascular stellate granulomas, vasculitis
Granulomas = palisaded histiocytes and multinucleated ginat cells, center necrosed with eosinophils
Vasculitis of arteris, veins, or capillaries
What od we see here?
Granulomas of Churg-Strauss
Centers have necrosis with prominent eosinophils.
What is microscopic polyangiitis?
MPA = pauci-immune vasculitis restricted to arterioles, venules, and capillaries
Glomrulonephritis, fever, myalgia and arthralgia, weight loss, ear, nose throat symptoms, skin involvement
pANCA positive
What do you see in lung pathology in microscopic polyangiitis?
Diffuse alveolar hemorrhage with neutrophilic capillaritis
No granulmoas, giant cells, eosiniophilia
No Ig deposits
What do we see here?
Neutrophilic capillaritis
Characteristic of microscopic polyangiitis, but also:
collagen vascular disease (lupus), Wegener’s, Goodpasture’s, Antiphospholipid Ab sydnrome, drug reaction, infection
What is diffuse alveolar hemorrhage?
Rare, but life-threatening complication of immune disorders
May present wiht fulminant respiratory failure
Hemoptysis
What is the most common cause of lung cancer?
Tobacco
Risk related to duration and amount of smoking
Not just nicotine: polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines
Who is more at risk for lung cancer, men or women?
Women
What are non-smoking risks for lung cancer?
Environmental/passive tobacco smoke
Radiation exposure (radon gas)
Air pollution)
cooking oil fumes and indoor coal/biomass burning
Prior lung disease
What is the most common cancer from asbestos exposure?
Lung cancer, NOT mesothelioma
What is the most common presentation of lung cancer?
Pulmonary nodules
Asymptomatic itself, but in a high risk patient it is cancer until proven otherwise
What do we see here?
Pulmonary nodule - cancer until proven otherwise
How do you evaluate a solitary pulmonary nodule?
common X-ray finding
Most are benign
Spiculated border is suggested of lung cancer
Smooth border can be benign or malignant
Cavitation may also benign or malignant
How do you diagnose primary lugn canncer?
Sputum cytology
bronchoscopy cytology
Transthoracic needle aspiration and cytology
Biopsy
What are histologic types of lung cancer?
Small cell
Non small cell (squamous cell, adenocarcinoma, large cell)
What ist he most predominant non-small cell carcinoma?
Adenocarcinoma
What are characteristics of squamous cell tumors?
Central location
may be cavitary
Strong association with smoking
What are characteristics of adenocarcinomas of lung?
Typically peripheral
Most in current or former smokers, but it is the most common tumor in non-smokers
What is lepidic adenocarcinoma (adenocarcinoma in situ)?
Lines alveolar spaces
may be indolent, with slow progression
May be multicentric
Can look like pneumonia
What is this?
Lepidic adenocarcinoma
What is squamous cell carcinoma of the lung?
Bulky, invades adjacent structures
Main stem or lobar bronchi, seen broncoscopically
Mets may be later
May cavitate
What is large cell lung cancer?
Subtype of non-small cell lung cancer
present as bulky tumors
May be aggressive with poor prognossi
What are carcinoid tumors?
Well-differentiated neuroendocrine tumors
Arise in central airways, present with wheezing, cough, and obstructive pneumonia
Better survival than small cell and non-small cell carcinomas
Can produce carcinoid syndrome, especially when metastasis
What is small cell carcinoma?
Has strongest association with smoking
Arises from pulmonary neuroendocrine cells
Typically present as central, perihilar masses and are associated iwth mediastinal lymphadenopathhy
What do we see here?
Small cell on left, non-small cell on right
What symptoms do you see in small cell carcinoma?
Paraneoplastic syndromes (release hormones)
Mets are extremely common at presentation
Poor survival
How does lung cancer present?
Most present at advanced stage, not good
Early lung cancers are asymptomatic
Detected as nodule on CXR or as symptoms (no bueno)
What symptoms are seen with lung cancer?
Airway symptoms (more commoni with squamous cell): cough, hemoptysis, dyspnea, post-obstructive pneumonia
Pleural symptoms (chest pain, effusion)
Mediastinal spread (hoarseness, diaphragm paralysis, SVC syndrome)
Distant spread (headache, weakness, seizure, bone pain, abdominal pain)
Other: (anorexia, weight loss, clubbing, paraneoplastic syndromes
What are pancoast tumors?
Lung cancers originating in the apex of the lung (superior sulcus or pancoast tumor)
Arm pain, weakness, due to brachial nerve involvement
Can cause Horner’s Syndrome: ptosis, meiosis, anhidrosis (due to cervical sympathetic invasion)
What do we see here?
Pancoast tumor (patient’s left side)
What paraneoplastic syndromes are common in lung cancer?
(seen in small cell carcinomas)
Cushing
SIADH
Eaton-Lambert myasthenic syndrome
Hypercalcemia is common in squamous cell carcinoma
Clubbing seen in any NSCLC
How is small cell lung cancer staged?
Limited : confined to single hemithorax
Extensive: spread beyond hemithorax
How is nonsmall cell lung cancer staged?
TNM system
Why do we stage lung cancer?
Gives us prognostic value:
5 yr survival:
Stage I : 60-70%
Stage II : 30-50%
Stage III : 10-20%
Stage IV: <10%
How do we treat NSCLC?
Is it resectable
Is it operable
Only surgery can cure
How do we treat lung cancers?
Surgery
Radiation
Chemo
What are the precursor lesions for lung cancers?
Squamous cell (squamous dysplasia and then carcinoma in situ)
Adenocarcinoma (Atypical adenomatous hyperplasia first)
Carcinoids (diffuse idiopathic pulmonary neuroendocrine cell hyperplasia first)
What is the most common carcinoma of the lung?
Adenocarcinoma
then squamous cell carcinoma
What are centraly located lung tumors?
squamous cell
Small cell
what are peripherally located lung tumors?
Adenocarcinoma
Large cell
Who gets squamous cell carcinoma?
Men, smokers
What is this?
Squamous cell carcinoma in situ of the lung
What systemic symptoms can you see in squamous cell carcinoma?
Hypercalcemia is the classic paraneoplastic syndrome
What can you see grossly/on CXR in squamous cell carcinoma of the lung?
Cavitation
What do we see here?
Squamous cell carcinoma of the lung
What is this?
Keratin “pearl” characteristic of squamous cell carcinoma of the lung
What is the characteristic histological finding of squamous cell carcinoma of the lung?
Keratin pearl
What lung cancer is associated with EGFR mutations?
Adenocarcinoma
What is atypical adenomatous hyperplasia?
Type II pneumocyte proliferation and/or clara cell proliferation
What is this?
Atypical adenomatous hyperplasia
What is broncioalveolar carcinoma (BAC) aka Adenocarcinoma in situ?
Entirely tumor cell sgrowign along existing alveolar septa (lepidic growth)
Non-mucinous
Important classificaiton for prognosis (almost 100% vs 60% of conventional adenocarcinomas)
What tumors have “ground glass” CXR appearance?
Bronchioalveolar carcinoma aka Adenocarcinoma in situ
What do we see here?
Adenocarcinoma in situ (aka BIC)
Like AAT but larger
What is minimally invasive adenocarcinoma?
Adenocarcinoma 3 cm or less; with lepidic growth and invasion
Solitary and discrete
Good prognosis
What is this?
Minimally invasive adenocarcinoma (MIA); like adenocarcinoma in situ, but invasive to one focus
Solitary and discrete, by definition
What are invasive lung adenocarcinomas?
most of adenocarcinomas
Typically glandular o papillary in structure
Solid
Peripheral with pleural puckering
What is large cell carcinoma?
Undifferentiated malignant epithelial tumor
Large nuclie, prominent nucleoli, moderate cytoplasm
What are small cell carcinomas?
Men, median age = 60
99% in smokers, very agressive with early mediastinal lymph node involvement
paraneoplastic (ADH, ACTH, PTH, Calcitonin, Gonadotropins, serotonin)
What are defining features of small cell carcinomas on pathology?
Gross: central/hilar, well-defined borders
Histologically: minimal cytoplasm, nuclear molding
What do you see here?
Neurosecretory granules that can be seen in neuroendocrine tumors of the lung
How do carcinoid tumors appear on histology?
Organoid, trabecular, palisaiding, ribbon or rosette-like arrangements of cells
Eosinophilic cytoplasm
Typical: <2 mitoses per 10 hpfs
Atypical: 2-10 mitoses per 10 hpf
What is the most common site of metastases?
The lung!
How do metastases typically present in the lung?
Multiple, discrete nodules scattered throughout lungs
What is SVC syndrome?
Gradual insidious compression/obstruciton of SVC
Bronchiogenic carcinoma is responsible for ~80% of SBC syndrome
Not good prognosis
What are the most common pleural tumors?
Metastatic more common than primary
What is malignant mesothelioma?
Majority due to asbestos exposure, not related to cigarette smoking
Men >>> women
Long latency period
How do malignant mesotheliomas present grossly?
Multiple small nodules that coalesce into a confluent rind
What od we see here?
Malignant mesothelioma
What are the three subtypes of mesothelioma?
Epithelial
Sarcomatoid
Bi-phasic
What supplies blood to the pleura?
Intercostal arteries = parietal pleura
Bronchial arteries = visceral pleuraW
What is the venous drainage of hte pleura?
Systemic veins = parietal pleura
Pulmonary veins = visceral pleura
Typically low pressure systems. In heart failure => pulm venous pressure increase, backup of blood. bad
where do parietal lymphatics drain?
Internal mammary chain anteriorly and internal intercostal chain posteriorly
Wehre do visceral pleura lymphatics drain?
Hilar and milddle mediastinal LNs
What is exudate?
Altered permeability of pleural membrane results in increased leakage of fluid and protein into pleural space
Result of inflammation or tissue disruption
What is Transudate?
Increased hydrostatic pressure and/or decreased colloid oncotic pressure
Typically teh result of fluid-avid states (CHF, cirrhosis, nephrotic syndrome)
How can you detect effusions?
Decreased breath sounds, fremitus; dullness to percussion
CXR
CT (w/ contrast)
Bedside ultrasound
When should you tap a pleural effusion?
Always except:
Less than 10mm of layering of free-flowing liquid on lateral decubitus
CHF with improvement with treatment
What is thoracentesis?
CXR guided or US guided
Done at one interspace below loss of fremitus and dullness
Pt upright
Big needle over the rib
What do you test for in the plerual fluid?
Protien, LDH, glucose
Cell count, differential
pH
Blood culture, gram stain
Cytology
AFB smear and culture
May do albumin, amylase, cholesterol, triglycerides and hematocrit
What are Light’s Criteria?
None met = transudate
Any met = exudate
Pleural fluid/serum protein ratio > 0.5
Plerual fluid/serum LDH ratio > 0.6
Plerual fluid LDH > 2/3 of upper limit of normal
What are transudative effusions?
CHF
Hepatic hydrothorax
Nephrotic syndrome
Peritoneal dialysis
Hypoalbuminemia
Urinothroax
SVC syndrome
What causes transudateive pleural effusion?
Increased hydrostaic pressure (CHF)
Decreased plasma oncotic pressure (hypoproteinemia, nephrotic syndorme, end stage liver disease)
Movement of transudative abdominal fluid (ascites)
What is hepatic hydrothorax?
Connection between thorax and abdomen + ascitic fluid
Right side is more common than left
Fluid is transudate
Tx the ascites
What are exudative effusions?
Infectious
Malignant
Collagen vascular disease (RA, SLE)
Pulm Embolism
Post Cardiac Injury Syndrome (PCIS, Dressler’s)
Asbestos
Chylothorax
Endocrine
Abdominal origin
What are parapneumonic effusions?
Simple - NBD, treat hte pneumonia
Complicated - have to drain
Empyema - emergency
What are signs and symptoms of pleural effusion?
Dypsnea, pleuritic chest pain, fever
Dull to percussion, decreased breath sounds, plerual friction rub
What differentiates empyema from pleural effusions?
High protein and LDH = exudate
Very low pH, very low glucose, pus = infectious
Wont always have bugs evident
Need to drain fully, treat with antibiotics and monitor for resolution
What are the types of pleural effusions?
Simple: pH > 7.2, no pus or bacteria present, no loculations
Complex: loculated, low pH
Empyema: pus, + Gram stain, + culture
What can cause pneumothorax?
Parietal entry: trauma, iatrogenic
Visceral entry: rupture of lung cyst, complication of mech. ventalation, necrosis due to toumor, infection, iatrogenic
What are causes of spontaneous pneumothorax?
Primary: tall, thin, smokers, wiht sub-pleural blebs
Secondary: to emphysema, PCP< CF, abscess, LCH, LAM
What is tension pneumothorax?
Air in pleural space under positive pressure from a one-way valve effect
Collapsed lung, redued venous return, hemodynamic changes/emergency
What is ARDS?
Acute Respiratory Distress Syndrome
What are features of ARDS?
Refractory hypoxemia, bilateral infiltrates, low lung compliance, increased wight at autopsy, No left atrial hypertension
What is the threshold for ARDS vs ALI?
ARDS = PaO2/FIO2 < 200
ALI = PaO2/FIO2 < 300
What are the causes of ARDS?
Sepsis
Pneumonia
Aspiration
Pancreatitis
Trauma
Burns
Transfusions
Toxic inhalation
Why do people die with ARDS?
They typically have multiorgan system failure
What is the pathophysiology behind ARDS?
Diffuse alveolar damage
Failure of alveolar capillary membrane (Flooding of alveolar airspaces with proteinaceous fluid
Activated neutrophils and macrophages release proinflammatory cytokines (TNFAα, IL1, and IL8)
O2 derived free radicals lead to injury
What are the phases of ARDS?
Exudative
Proliferative
Fibrotic
Is imaging useful in ARDS?
Not really - snowstorm like appearance.
How do you manage ARDS?
Treat underlyign cause
Lung protective strategy of lung ventilation (avoid volutrauma nad barotrauma)
Provide supportive care
Is mechanical ventilation/Oxygen good for ARDS?
Can worsen lung injury
Over distention of alveoli that can induce inflammation
Repetitive alveolar collapse and opening causes shear stress
Oxygen can generate free radicals
What is DAD?
Diffuse Alveolar Damage = histologic finding
What is AIP?
Acute Interstitial Pneumonia
(idiopathic diffuse alveolar damage)
What is diffuse alveolar damage?
Caused by diffuse alveolar capillary/epithelial dmaage
Rapid onset of severe life-threatening respireotary insufficeincy, cyanosis, and severe areterial hypoxemia
Refractory to O2 therapy
May lead to extrapulmonary multisystem organ failure
CXR show diffuse alveolar inflitration
How does DAD occur?
Injury to vascular endothelium and alveoli results in excess vascular fluid and protein leakage (early on) and then cellular necrosis, epithelial hyeprplasia, inflammaiton, and fibrosis (late)
What is the pathognomonic finding in DAD?
Hyaline membranes
As well as exudate into alveoli (pulmonary edema, hemorrhage)
What are gross findings of ARDS lungs early on?
Wet, boggy, airless, heavy
What do we see here?
Exudative phase of diffuse alveolar damage
Interstitial and alveolar edema, fibrin exudation, and hyaline membranes
Mild inflammation
What do you think when you see hyaline membranes?
Diffuse alveolar damage (ARDS)
What is eosinophilic pneumonia?
Intra-alveolar fibrin, macrophages, abundant eosinophils, and eosinophil microabscesses
+/- an organizing pneumonia
Sensitive to steroids
What is acute eosinophilic pneumonia?
May present with respiratory failure clinically (ARDS)
May not have periopheral blood eosinohpilia
Asthma history ist ypically not present
has hyaline membranes essentially identical to those of DAD, PLUS eosinophilia
What is organizing pneumonia?
“airspace organization” is loose connective tissue in alveoli seen commonly in lung injury as the lung attempts ot repiar
Can be primary (OP pattern), component of another process (HSP, acute pneumonia), or secondary (tumor, granuloma, etc)
What does oganizing pneumonia look like histologically?
Patchy, bronchiolocentric organizing pneumonia +/- fibroblastic plugs
minimal chornic ifnlammation in adjacent alveoli
Intervening lung is more or less normal
NO other findings
What od we see here?
Organizing fibroblastic tissue within airspaces (organizing pneumonia)
