Loss of lung volume due to alveolar collapse Decreased oxygenation V/Q mismatch 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)
Clinical Diagnoses 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)
Histological Pattern 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 Can include: Desquamative Interstitial Pneumonia (DIP DAD (in ARDS) Non-specific Interstitial Pneumonia (NSIP) Respiratory Bronchiolitis 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 Adenocarcinoma 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 Horner's Synd. 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
Coronavirus China, Hong Kong, Singapore, Canada 2003 Outbreak, 8,000 sick and 700 deaths US not infected (only 8 people)
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 not spongy
What characterizes the acute phase of ARDS?
HYALINE MEMBRANES 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?
increased age bacteremia/sepsis multisystem organ failure
What causes respiratory compromise after the cute phase in ARDS?
If normal function returns after ARDS, when does this occur?
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?
Centrilobular Panlobular Septal Irregular
What does Emphysema look like on gross appearance?
"moth eaten" Hyperinflated lungs Bullae
What does Emphysema look like in histological appearance?
free floating alveolar septa NO FIBROSIS Destruction of elastin, collapse and trap air on exhalation
Describe Centrilobular Emphysema:
Smoking 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:
Rare Margins of the lung, sub pleura, upper lobes May form bullae (large holes in alveoli) can lead to pneumothorax - atelctasis
Describe Irregular Emphysema:
Paracicatricial Surrounding a scar, the scar contracts and pulls alveoli air sacs open (only in extensive scarring) asymptomatic
How does a patient with Emphysema present?
Pink Puffers 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?
SMOKERS Urban Dwellers
What are typical inhaled irritants causing Chronic Bronchitis?
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?
Blue Bloaters 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
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% Hyperventilation 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 Thick sputum 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?
Hypoxia Hypercapnia Respiratory Acidosis
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
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?
Autosomal recessive 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?
Asthma Churg-Strauss 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?
FIBROSIS bilateral patchy lung involvement epithelial and BM cells, collagen, elastin, fibroblasts dyspnea, hypoxia, increased work to breathe V/Q mismatch pulmonary hypertension and cor pulmonale
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 relentless poor prognosis
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 HIV 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?
Masson Bodies 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?
Type IV HSR - cell mediated Unidentified Antigen CD4 T Cells, proliferation of Th1 cells (intra-alveolar and interstitial) secretion of IFNy and IL-2 Polyclonal hypergammaglobulinemia
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?
Asymptomatic 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?
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 causes pneumnia
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) Immunoglobulin Deficiency 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?
IVDAs (shoot up into a vein, bacteria travels to right heart, then can enter lungs)
What are two complications of pneumonia caused by Staph. aureus?
How does Atypical Community Acquired pneumonia present?
"Walking Pneumonia" 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 mostly self-limited 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
Atypical lymphoid cells Permeation of vessels (often not necrotic) Necrosis (infarct like, palisaded rim) Angiodestructive
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?
Granulomatous inflammation Localized lesion
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?
silicosis 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?
Type IV 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 Positive Test: 5mm HIV 10mm HCP (health care personnel) 15mm Public 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?
Unexposed/Unsensitized Immunocompetent 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 Complex: Ghon focus (consolidation with necrotic center) local lymphatics 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 central necrosis
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)?
M. avium-intracellulare M. kansaii M. abscessus
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?
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)?
Coronavirus 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?
thromboembolism 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 Oral Contraceptives 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 cor pulmonale
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?
Pulmonary arteries Bronchial arteries
When does ischemic necrosis in the lung occur?
When there is concomitant CV compromise wedge shaped, peripheral, pale
How much of the pulmonary circulation needs to be occluded for sudden death to occur?
60% 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 COPD Restrictive lung disease (interstitial) Recurrent emboli 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?
What changes are seen in small arteries and arterioles in pulmonary hypertension?
medial hypertrophy reduplication of internal and external elastic lamina thickening
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) TGFB
Who does Primary pulmonary hypertension occur in?
How does Primary pulmonary hypertension present?
fatigue, syncope, short of breath, chest pain cyanosis 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) Alveolar hemorrhage Patchy necrosis of alveolar septum (where antibodies are being taken up by PMNs and Macs) Septal thickening and Type II cells rounding up Intra-alveolarhemosiderin
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 Immunosuppressive therapy 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?
ANCA-PR3 (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?
cavitary lesions with central necrosis Keratin pearls that look whorled Intracellular bridges that have a prickled appearance
What immunohistochemical markers determine squamous cell carcinoma?
p63 cytokeratin 5/6 cytokeratin 903
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?
smokers (99% of the time there is smoking history)
What are the characteristics of small cell carcinoma?
Centrally located 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) extensive necrosis
What immunohistochemical markers determine small cell carcinoma?
keratin stain chromogranin synaptophysin CD56 (it is a neuroendocrine tumor)
What are some of the para-neoplastic syndromes associated with small cell lung cancer?
ACTH production ADH production Gastrin-releasing peptide Calcitonin
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) atelectasis
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. Horner Synd. Pancoast Synd. Paraneoplastic Syndromes
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 ipsilateral enopthalmus
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 Horner's syndrome 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) Gonadotropins (gynecomastia)
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?
Crizotinib 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?
Kulchitksy cells (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?
Centrally located More "well behaved" but still malignant, localized but can still metastasize Resectable Good prognosis
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 Asthma attacks
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