Atelectasis, ARDS, COPD, Pulmonary Edema, Asthma Pathology

A 16 year old male is rushed to the ER after a *stab would to the chest* during a fight. Exam shows a 1cm *entry wound* at the 5th intercostal space. RR is 33 and BP is 90/50mmHg. CXR shows air in the right pleural space. Which of the following is the expected complication? A. Atelectasis B. Chylothorax C. Diffuse alveolar damage D. Empyema E. Pyothorax

A) Atelectasis: a major complication of a pneumothorax (air in the pleural space) is a compressive atelectasis (in which the lung collapses)

What is the name for the collapase of lung tissue affecting part or all of one lung; alveoli are deflated?

Atelectasis

What is the microscopic mechanism of damage in chronic bronchitis? (bronchial mucosa and submucosa)

Bronchial mucosa: - epithelium: squamous metaplasia, dysplasia - increased number of goblet cells (hyper secretion of mucus) Submucosa: - hypertrophy of glands - increased Reid index (normal= 0.4) --> increased thickness

A 45 year old male has smoked *two packs of cigarettes per day for 20 years*. For the past *4 years*, he has had a *chronic cough with copious mucoid expectoration*. During the past year he has had *multiple respiratory infections*. He has also developed *difficulty breathing, tightness in the chest and wheezing*. Which of the following pathologic conditions is most likely responsible for his clinical condition? A. alpha-antitrypsin deficiency with panlobular emphysema B. Centrilobular emphysema C. Chronic bronchitis D. Cystic fibrosis with Bronchiectasis E. Hypersensitivity with restrictive lung disease

C- Chronic bronchitis

What type of lung disease is characterized by airflow limitation that is not fully reversible?

COPD - usually both progressive and associated with an abnormal inflammation - response of the lungs to noxious particles or gases

Compare asthmatic bronchi to normal:

- submucosal edema - thickened basement membrane - mucous cell debris

What are the two types of asthma?

1) extrinsic (atopic) asthma 2) intrinsic (non-atopic) asthma

what does pulmonary edema look like on X-ray?

"bat wings" = increased vascular filling - or kerley B lines = horizontal lines--> left heart failure most likely

What is the clinical presentation of chronic bronchitis?

"blue bloaters" = hypoxia, cyanosis, weight gain, expanded lower diameter of rib cage, dyspnea 1) productive cough due to excessive mucous production 2) cyanosis - (blue bloaters)- mucus plugs trap carbon dioxide; increased PaCO2 and decreased Pa O2 3) Increased risk of infection and cor pulmonale (abnormal enlargement of the right side of the heart as a result of disease of the lungs or the pulmonary blood vessels) CXR: enlarged heart with prominent blood vessels (cor pulmonale)

What will an Xray of ARDS show?

"white out on X-ray" - pulmonary edema, could also be due to cardiogenic cause

What is Kartagener's Syndrome? what are the patients at increased risk of developing?

*Immotile cilia syndrome* increased risk of developing *bronchiectasis* - Autosomal recessive (possibly on 15q in some types) - infertility - immotile cilia due to defect of dynein arms - bronchiectasis -situs invertus - sinusitis

If a post-op patient develops a fever and difficulty breathing what might you be suspicious of?

*obstructive atelectasis* - this is why patients are asked to do *post operative incentive spirometry* post op to prevent collapse of the lung

What type of pneumothorax arises from penetrating chest wall injury?

*tension pneumothorax* = MEDICAL EMERGENCY (can cause steadily worsening oxygen shortage & low blood pressure and death) -amount of air in chest increases markedly when a one way valve is formed by an area of damaged tissue (i.e. Gun shot wound, knife wound) - treat with needle decompression & then chest tube dx: trachea is pushed to the opposite side (X-ray shows whole mediastinum mushed to the opposite side of the chest)

What are the key morphologic findings of emphysema?

- *permanent dilation of air spaces* distal to terminal bronchioles = this is why patients have large lungs and large chest diameter - *destruction* of alveolar septae

What are the obstructive lung diseases?

- COPD = chronic bronchitis & emphysema - bronchiectasis - asthma (extrinsic and intrinsic)

What does the microscopy of ARDS look like?

- alveolar septa = thickened by edema; sparse inflammatory infiltrate - alveoli= lined by eosinophilic hyaline membranes (pink = protein)

What does centre-acinar emphysema look like on CT?

- black = worse - periphery is affects, whole lope almost

How can you diagnose ARDS?

- cap permeability increased - cap wedge pressure- normal - lung compliance decreased - V/Q mismatch <1 - increased work of breathing (hypoxia and cyanosis) *clinical features: rapid onset of dyspnea, not responsive to O2 therapy, respiratory failure ABGs: severe hypoxemia, acute respiratory acidosis

How is chronic bronchitis diagnosed?

- chronic productive cough lasting at least 3 months over a minimum of 2 years (highly associated with smoking) - characterized by hypertrophy of bronchial mutinous glands - leads to increased thickness of mucous glands relative to bronchial wall thickness (reid index increases to >50%, normal is <40%) *** chronic inflammation of bronchus is NOT a prominent features (do not have inflammatory cells)

What are the findings in sputum of asthma patients?

- curshmann spirals (whorls of shed epithelium, spiral shaped mucous plugs) - charcot-laden crystals: from IgE+ Eosinophils = eos release lisinophilic lipase when they break and it forms a crystal

What is Acute Respiratory Distress Syndrome (ARDS)?

- diffuse damage to the alveolar capillary interface (*diffuse alveolar damage*) - *leakage of protein-rich fluid* leads to edema that combines with *necrotic epithelial cells* to form *hyaline membranes* in the alveoli

Bronchiectasis (gross):

- dilated bronchi and bronchioles extending upto pleura (honey combed appearance)

What does emphysema look like under microscopy?

- dilation of air spaces - destruction of septal walls (wispy walls) - chronic inflammation of wall may be present

Chest Xray of Chronic Bronchitis:

- enlarged heart with prominent blood vessels

What is bronchial asthma?

- hyper-reactive airways - episodic vasospasm - triggered by certain stimuli *widespread narrowing of air passages* - relieved spontaneously or with therapy

What does restrictive lung disease look like on a flow-volume loop?

- ice cream cone - the whole lung is clamped down (fibrosis) and so the volume of air in and out is decreased

What does centri-acinar emphysema look like on CT?

- intact lung paranchyma = grayish - destroyed lungs are closer to the main bronchus and the rest is spared

What does pulmonary edema look like on microscopy?

- pink staining material in the alveoli and interstitial spaces = edema fluid (RBC)

What does atelectasis look like on gross?

- rubbery lung-- surface can be depressed and dark

What is risks are associated with centri-acinar emphysema?

- smokers - coal miners pneumoconiosis

What factors can lead to emphysema?

- tobacco smoke - air pollutants - other factors: occupational exposure, infection, familial, genetic

Emphysema (gross)

- voluminous, pale - rounded edges - sub pleural bullae (>1cm by rupture of adjacent air spaces) - blebs: rupture of alveoli into sub-pleural interstitial tissue * blebs: they balloon out and can pop rupturing the visceral pleura (parietal stays intact) which can cause a spontaneous (secondary) pneumothorax

What does atelectasis look like on X-ray?

- wedge shaped opaque area on chest X-ray (triangle shape showing where the lung has collapsed)

What are the various types of pneumothorax?

1) Spontaneous Pneumothorax- due to rupture of an emphysematous bleb (seen in young adults)--> trachea shifts to the side of the collapse a) Primary spontaneous pneumo: occurs without an apparent cause and in the absence of significant lung disease B) Secondary spontaneous pneumo: occurs in the presence of pre-existing lung pathology (ex: COPD, asthma, etc.) 2) Tension pneumothorax: arises with penetrating chest wall injury - air enters the pleural space, but cannot exit - trachea is pushed opposite to side of injury - medical emergency; treated with insertion of a chest tube

What causes bronchiectasis?

1) bronchial obstruction - foreign body - mucous - tumor - enlarged LN 2) necrotizing pneumonias 3) Hereditary & congenital factors - congenital bronchiectasis: developmental defect of bronchial system - cystic fibrosis - immotile cilia syndrome (Kartagener's syndrome) AR, infertility (immotile cilia due to defect of dynein arms), bronchiectasis, situs invertus and sinusitis

What are the 2 major classifications of emphysema?

1) centri-acinar emphysema: (>95%) proximal area of destruction that is not all the way to the end of the lung alveoli just surrounding the respiratory bronchioles 2) pan-acinar emphysema (panlobular): whole thing is destroyed to the end of the alveoli

What is a complication of treatment for NRDS (or hyaline membrane disease)?

1) hypoxemia increases risk for persistence of patent ductus arterioles and necrotizing enterocolitis 2) supplemental oxygen increases risk for free radical injury = retinal injury leads to blindness, lung damage leads to bronchopulmonary dysplasia

What are the 2 types of atelectasis?

1) obstructive atelectasis 2) Compression atelectasis

What are the 3 types of chronic bronchitis?

1) simple chronic bronchitis - productive cough but no physiology E/O airflow obstruction 2) chronic asthmatic bronchitis: hyper-reactive airways with intermittent broncho-spasm and wheezing (need inhaler) 3) obstructive chronic bronchitis: heavy smokers, chronic airflow obstruction, with E/O associated emphysema

What causes chronic bronchitis?

1) smoking: (90%) - incidence 4-10 times higher - impairs ciliary movement - inhibits function of alveolar macrophages - hypertrophy & hyperplasia of mucus secreting glands 2) atmospheric pollution - incidence higher in urban population - SO2, NO2, particulate dust, toxic fumes 3) occupation - cotton mills (byssinosis), plastic factories (exposure to organic/inorganic dust) 4) Infection - bacterial/viral/ mycoplasmal infections occur secondary to bronchitis 5) Family % genetic factors - poorly defined; passive smoking

A study is conducted of individuals who smoked at least *one pack of cigarettes per day for 30 years*. These individuals undergo pulmonary function testing, and a large subset is found to have *decrease FEV*, *normal to decreased FVC*, and *FEV1/FVC ratios less than 70%*. Autopsy data from this subset of individuals in the study with a low FEV1/FVC ratio are analyzed. Which of the following respiratory tract structures in the lungs is likely to be affected most by the underlying disease? A. Alveolar duct B. Alveolar sac C. Bronchi D. Respiratory bronchiole E. Terminal bronchiole

D) respiratory bronchiole- 95% emphysema w/ smoking = centri-acinar emphysema which starts at respiratory bronchiole and stays around there

A 10 year old male dies following a severe episode of *status asthmaticus*. Microscopic exam of lung at autopsy is shown. Which of the following best describes the pathologic features evident? A. Destruction of the walls of airspaces without fibrosis B. Hyaline membranes and interstitial edema C. Interstital fibrosis of lung parenchyma D. Intra-avlveolar hemorrhage and exudates neutrophils E.Smooth muscle hyperplasia and basement membrane thickening

E) smooth muscle hyperplasia and basement membrane thickening (asthma)

What are the cytokines involved with asthma/ type I hypersensitivity and what do they do?

IL 4 (mediates class switch to IgE) IL-5 (attracts eosinophils) IL-10 (stimulates Th2 cells and inhibits Th1 cells)

What lab would be increased in atopic asthma but normal in intrinsic (non-atopic) asthma?

IgE

What are clinical manifestations of a1AT deficiency ?

Liver: obstructive jaundice in infancy + cirrhosis in early childhood Lung: panacinar emphysema

What is the difference between obstructive atelectasis and compressive atelectasis?

Obstructive atelectasis: - collapse of the alveoli due to airway obstruction (ex: exudate, parasites, food particles) - mediastinal shift towards atelectic lung Compressive Atelectasis: - collapse of the alveoli due to large intra-thoracic masses that compress the lung (ex: abscesses, tumors, pericarditis,

What are the differences between obstructive (emphysema) and restrictive (fibrosis) lung diseases

Obstructive: - increase total lung capacity, residual volume, and functional residual capacity - decreased FEV1, FVC, FEV1/FVC, Peak flow Restrictive: - increased FEV1/FVC (or normal) - decreased TLC, FEV1, FVC, Peak flow, Functional residual capacity, residual volume

What test is used to distinguish between obstructive lung disease and restrictive?

PFT = pulmonary function tests Obstructive: - very decreased FEV1 - mildly decreased FVC - decreased FEV1/FVC ratio - TLC increased due to air trapping Restrictive: - TLC decreased - FVC is more decreased than FEV1 - FEV1/ FVC ration: normal or increased

What are the clinical manifestations of Emphysema?

Pink puffers -pink complexion - dyspnea - increased residual lung capacity and volume - decreased expiratory flow rate and diffusing capacity (ventilation /perfusoin- V/Q mismatch secondary to emphysema-related destruction of blood vessels) - retraction of accessory respiratory muscles - thin

Which type of pneumothorax occurs without an apparent cause and in the absence of significant lung disease?

Primary spontaneous Pneumothorax- usually due to an emphysematous bleb

Spirometry measures lung volumes except for__.

Residual lung volume + Total Lung Capacity

What type of pneumothorax occurs in the presence of pre-existing lung pathology (ex: COPD, asthma, etc.)?

Secondary spontaneous pneumothorax

What injuries can lead to Acute Respiratory Distress Syndrome (ARDS)??

So many causes: - *sepsis* - infection - shock - trauma - aspiration - pancreatitis - DIC (disseminated intravascular coagulation) - hypersensitivity reactions - drugs activation of neutrophils induces protease and free radical-mediated damage of type I and II pneumocytes

What does the asthma bronchi look like microscopically? (submucosa, smooth muscle)

Submucosa: - hypertrophy of mucus glands - goblet cell hyperplasia smooth muscle: - hypertrophy of bronchial smooth muscle wall

Gross pathology of chronic bronchitis:

Wall: thick (congestion + edema) Lumen: mucus plugs + purulent exudate

What is COPD?

a group of diseases characterized by airway obstruction; the lung does not empty, and air is trapped (ex: chronic bronchitis + emphysema)

What is para-septal emphysema?

adjacent to areas of fibrosis/atelectasis - common cause of spontaneous pneumothorax - can be in both places (central or periphery)

What is the name for the disease when asthma symptoms are triggered by an allergic reaction?

allergic asthma (atopic/extrinisic) - airway obstruction and inflammation - partially reversible with medication (B2 agonist) - always associated with allergy

What is the name for an abnormal permanent dilation (of bronchi and bronchioles) due to chronic necrotizing infection?

bronchiectasis - dilation of bronchi and bronchioles (> 2mm in diameter) Secondary to: inflammation of bronchial walls

How can blebs in emphysema become a problem?

can lead to secondary spontaneous pneumothorax: the blebs balloon out and can pop rupturing the visceral pleura (parietal stays intact)

How can you distinguish between pulmonary edema caused by ARDS vs a cariogenic cause (like CHF with left heart failure)?

capillary wedge pressure - ARDS = normal capillary wedge pressure - Cardiogenic cause (left heart failure)= increased capillary wedge pressure

What are the 2 possible mechanisms of emphysema?

destruction of lungs elastic recoil due to imbalance of proteases and antiproteases 1) either from excessive inflammation, where neutrophils release more proteases 2) or from decreases amount of antiproteases due to deficiency

What does centri-acinar emphysema look like on microscopy?

destruction of the walls of the respiratory bronchi and increased dissension of alveoli is clustered to the central bronchi

Where amongst the pulmonary bronchial tree is the dilation found in emphysema?

distal to the terminal bronchioles

Which disorder will have collapsed bronchioles & enlarged alveoli?

emphysema - *permanent dilation of air spaces* distal to terminal bronchioles - *destruction* of alveolar senate

What does microscopy of bronchiectasis show?

epithelium: normal/ulcerated/squamous metaplasia wall: acute + chronic inflammation = muscle destruction and fibrosis

What age is typically affected by extrinsic (atopic) asthma vs Intrinsic (non-atopic) asthma?

extrinsic asthma- childhood intrinsic asthma- adult (typically)

What is pulmonary edema? cause? treatment?

fluid inside the alveoli - leads to impaired gas exchange and may cause respiratory failure -Causes: 1) failure of left ventricle of heart to remove blood from pulmonary circulation 2) injury to lung parenchyma 3) injury to vasculature of lung treatment: - improve respiratory function - treat underling cause of disease - avoid further damage to lung

What gives a genetic predisposition to atopic asthma?

genetic predisposition for type I hypersensitivity ("atopy") - 5q gene cluster: for cytokines IL-3, IL4, IL5, IL9, and IL-13 - gene for ADAM 33 (metalloproteinase) in smooth muscle proliferation

What is the difference between hyaline membrane disease and ARDS?

hyaline membrane disease (neonatal respiratory distress syndrome): disease of prematurity, due to inadequate surfactant levels and is a relative common condition resulting from *insufficient production of surfactant results in collapse of alveoli & production of hyaline membranes* = young & infants ARDS: (acute respiratory distress syndrome) severe, life threatening medical condition characterized by *widespread inflammation in the lungs resulting in hyaline membranes which can be set off by a number of triggers and eventually causes the death of type II pneumocytes leading to decrease in surfactant* = adults

What is the pathogenic mechanism of bronchitis? (large airways vs small airways)

hyper-secretion of mucus Large Airways: - submcusal glands hypertrophy in trachea and bronchi microscopically - stimulated by proteases (released from neutrophil elastase, cathepsin, MMPs) on the cellular level Small airways: - goblet cell metaplasia with mucus plugs in lumen grossly - clusters of pigmented alveolar macrophages microscopically - inflammatory infiltrate microscopically - fibrosis of bronchiolar wall microscopically

What does chronic bronchitis look like on microscopy?

hypertrophy of bronchial mucinous glands

What causes the air trapping in emphysema?

loss of elastic recoil and collapse of airways during exhalation results in obstruction and air trapping - due to imbalance of proteases and antiproteases (either from excessive inflammation, where neutrophils release more proteases or from decreases amount of antiproteases due to defieciency) (decreased elasticity, increased compliance of the lung)

What is the name for the disease when asthma symptoms are triggered by factors not related to allergies (ex: exercise, respiratory infection, etc)?

non-allergic (intrinsic, non-atopic) asthma - characterized by airway obstruction and inflammation that is at least partially reversible with medication - NOT associated with an allergic reaction

Compare the FEV1/FVC ratio in Obstructive vs Restrictive Airway disease?

obstructive: FEV1/FVC ratio is decreased restrictive: FEV1/ FVC ratio is increased

What does the gross lung of an asthmatic look like?

occlusion of bronchi and bronchioles by mucus plugs

Why is bronchiectasis considered an obstructive lung disease?

permanent dilation of bronchioles and bronchi = loss of airway tone results in air trapping

What is a peak expiratory flow (PEF) or peak expiratory flow rate (PEFR)?

person's maximum speed of expiration as measure with a peak flow meter, used to monitor a persons ability to breathe out air (measure airflow through bronchi and thus degrees of obstruction of the aways) - can be used at home or hospital setting to monitor obstructive diseases like asthma

What is the flow volume loop?

plot of inspiratory and expiratory flow against volume during the performance of maximally forced inspiratory and expiratory maneuvers - changes in contour of the loop can help diagnosis and localize airway obstruction and patterns are found in some forms of restrictive disease as well - positive numbers= flow out of lung (expiration) - negative numbers = flow into lung (inspiration)

What is the name for an abnormal collection of air or gas int he pleural space separating the lung from the wall?

pneumothorax

What is alpha 1 antitryptase?

protease inhibitor (elastase inhibitor in the lungs) - glycoprotein, normal constituent of alpha1 globulin fraction of plasma proteins - made from a gene on chromosome 14 - homozygous normal = PiMM - homozygous deficiency = PiZZ

What does COPD look like on a Flow-volume loop?

rocking chair - bottom of the loop is normal - top part of the loop is smaller with increased convexity * less air is leaving the lung in 1 second

What is status asthmaticus?

severe asthma unresponsive to repeated sources of beta agonist therapy such as inhaled albuterol, levalbuterol, or subcutaneous epinephrine intervention include IV meds, aerosolized medicaments and therapy including mechanical ventilation

What is most common cause of emphysema?

smoking, reasons: 1) pollutants in smoke lead to excessive inflammation and protease-mediated damage (10x more phagocytes & PNMs= high elastase) 2) oxidant in smoke inhibits alpha 1 AT (decreases the anti-elastase activity) (results in centriacinar emphysema that is most severe in upper lobes)

What is the mechanism of injury of ARDS?

some insiting factor (sepsis, infection, trauma, drugs) causes activation of *neutrophils* induces *protease* and *free radical-mediated damage* of type I and II pneumocytes = exudative fluid leaks out into the alveolar interstitium cytokines: IL-8, IL-1, TNF

What does a lung with ARDS look like on gross?

stiff, heavy, non compliant

What is the Reid Index?

used post mortem for research; definition: ratio between the thickness of the submucosal mucus secreting glands (b-c) and the thickness between the epithelium and cartilage that covers the bronchi (a-d) - *increased in chronic bronchitis*