(From Path book and lecture, 22-25 Jan 2001, by Brian Buschman)
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In the normal lung all of the respiratory tract is covered with columnar epithelia except for the vocal folds (and of course the very small channels) which are covered by stratified squamous.
We have two main congenital lung problems:
1) Congenital cysts which are cysts made up of detached sections of the primitive foregut that develop like improperly placed sections of bronchiole.
2) Bronchiopulmonary sequestration involves lung lobes that are detached from both the pulmonary circulation and the airways. They may be either extralobar or intralobar.
There are three types of atelectasis:
1) Obstructive atelectasis is lung deflation because of blockage of the respiratory unit. In this case it is blocked. The air is absorbed into the capillaries but new gas is not put back into it.
2) Comprehensive atelectasis is collapse from a compressive force like a pneumothorax or pleural effusion.
3) Patchy (microatelectasis) is a loss of expansion from many factors, including loss of surfactant. This is seen in NRDS and ARDS.
Pulmonary edema may be due to hemodynamic causes like L. heart failure, decreased oncotic pressure and what not or it may be caused by microvascular injury like infection, aspiration, drugs, trauma and so forth.
It may also be caused by ARDS which has diffuse alveolar capillary damage. Pulmonary edema, hyaline membrane, hypoxemia. It is very fatal, unresponsive to O2 and survivors have a high degree of fibrosis.
When viewing pulmonary edema grossly you see stretching of the lobular pattern. Microscopically you see heart failure cells floating around.
Pulmonary embolism can prove to be a problem epically in patients that are sitting around too much. Most pulmonary emboli are thromboemboli from the deep veins of the legs. Large ones cause sudden death, small ones pulmonary infarcts.
Emboli may also be fat emboli from bone marrow released with trauma or amniotic fluid emboli. Amniotic fluid is full of squamous cells.
Pulmonary circulation usually has 1/8 of the pressure of systemic circulation but in some patients they can get up to ¼ or more.
It is usually caused by COPD, chronic interstitial lung disease, recurrent pulmonary emboli and heart disease with a L-to-R shunt.
It leads to thickening of the vessels. About 10% suffer vasospastic conditions like Raynaud’s phenomenon (pain/ischema of peripheral things from vasospasm).
One of the effects of pulmonary hypertension is plexogenic arteriopathy where a plexus of capillaries develop within an artery.
Diffuse pulmonary disease includes obstructive diseases which have difficulty on expiration due to anatomic narrowing or decreased elastic recoil or from restrictive disease with inspitatory expansion problems from reduced lung capacity.
COPD usually includes:
1) Emphysema (“pink puffers”)
2) Chronic bronchitis (“blue bloaters”)
3) Bronchial asthma
4) Bronchiectasis
Emphysema is the over expansion of airways distal to the terminal bronchioles with destruction of their walls (and hence loss of elastic properties). Types of emphysema include:
1) Panacinar emphysema involves the enlargement of all acini in the given area. The type is related to a1-antitrypsin deficiency.
2) Centroacinar emphysema has enlargement of central parts of acini with normal terminal sections.
3) Paraseptal (distal acinar) emphysema includes enlargement of the distal parts. The parts that are subpleural.
4) Irregular emphysema includes atypical blebs with no specific pattern.
The pathogenesis of emphysema is related to the balance b/t the synthesis and destruction of elastic fibers. This is related to the balance b/t protease and protease-inhibitors. Patient with a1-antitrypsin deficiency develop it at a young age.
Tobacco smoke recruits PNLs of macrophages that release proteases and inactivate a1-antitrypsin.
Emphysema is most common in older patients. They present with weight loss, barrel chest, dyspnea with long expiration phases. They show forced expiration that leads to the name “pink puffers.”
Death is usually due to respiratory failure, CHF or rupture of bullae leading the tension pneumonothorax.
Chronic bronchitis is an “inflammatory cause of COPD” that presents as a persistent productive cough for at least 3 months our of the past two years. It is caused by smoking and infections are secondary.
It is caused by a chronic irritation of the bronchial mucosa that leads to excess mucous production. The Reid index is a ratio of the thickness of the wall and mucus membranes to the thickness of the epithelium and cartilage. It is usually 0.4.
Chronic bronchitis is composed of goblet cell metaplasia in the bronchioles. The epithelium may show metaplasia in a pre-cancerous way but that is rare.
Clinically patients are overweight and cyanotic hence the name “blue bloaters.” You need a “good hack” for a sputum culture. To see if you have one look for coal dust or hemosiderin macrophages to know if mucous is hacked from the lung. It should appear like asthmatic mucous with eosinophils, neutrophils and plasma cells.
Bronchial asthma is cause by paroxysmal bronchospasms. There are two types:
1) Extrinsic asthma which is IgE mediated hypersensitive reaction triggered by environmental antigens.
2) Intrinsic asthma is non-allergenic and triggered by respiratory tract infections or drugs.
If is now believed that bronchial asthma is an immune response and not a bronchospasm that happens. Therefore it is better to treat with anti-inflammatories rather than steroids.
An asthmatic will have over inflated lungs with patchy atelectasis and occlusion of some airways b/v of mucus.
Clinically patients with extrinsic asthma will get better after a couple of years. Unfortunately intrinsic asthma does not improve. In some causes it can lead to cor pulmonale or infection.
Bronchiectasis is a destruction and dilation of bronchi because of chronic necrotizing infections. Patients are predisposed by mucus plugs, CF, immotile cilia and such things that lead to infection.
It is caused by a “stretch it till it breaks.” It has a loss of bronchi. Often it’s from chronic infection like TB or 2o to foreign body obstruction.
Pulmonary infections are usually brought on by impairment of the normal pulmonary defense mechanisms including:
1) Loss of the cough reflex.
2) Decrease in IgA secretion.
3) Branchial obstruction.
4) Pulmonary edema
5) Loss of phagocytic function
Bacterial pneumonias are usually either broncho or lobar.
Bronchopneumonias are usually bacterial and show a patchy consolidation of lung parenchyma. Infections are usually from streptococci but may also be from staph, pneumococci, hemophilus, pseudomonas and E. coli. Staph is bad because it produces abscesses.
With proper treatment there is complete resolution without fibrous scaring.
Lobar pneumonia is usually caused by strep pneumonia called pneumococcus. Klebsiella will also cause it.
If untreated the lobar pneumonia will follow the following stages:
1) Congestion
2) Red hepatization where it has a liver like consolidation.
3) Gray hepatization which has a gray superlative exudate.
4) Resolution involving enzymatic degradation of exudate and restoration of normal structure.
Interstitial pneumonia is usually caused by a virus or mycoplasm. They induce lung parenchyma inflammation without consolidation. The walls become thick as they are infiltrated by mononuclear cells.
Hyaline membranes form. Viruses cause necrosis of alveolar epithelia. Pnemunocytes type II replace the damaged type I’s. Sometimes bacterial pneumonia will occur secondary to interstitial pneumonia.
Lung abscesses are localized suppurative (pus forming) infiltrations of lung that are usually caused by Staph, anaerobes or mixed infections. They can develop from any pneumonia.
If you see a hole in a lung (x-ray) you must work to rule out a bronchiogenic cyst.
TB is a lung infection by M. tuberculosis that causes caseating granulomas called Ghon foci. In 1o TB the Ghon foci will form and then usually calcify as the disease goes away. In some the Ghon foci remain active but in a latent stage and reactivates when the immune system is suppressed. Either way a patient will develop a positive PPD skin test.
It can become reactivated later in life and presents with fever, sweats, weight loss, cough and hemoptysis. Sputum will show acid-fast bacilli. Reactivation tends to show upper lobe involvement.
ILD is a group of conditions that all show diffuse inflammation of alveolar walls that lead to fibrosis and so called “Honeycomb lung.” They all follow a similar set of events:
1) Initially they have injury to alveolar epithelium (ARDS)
2) Early acute events with infection and inflammation. Changes ocure as the tissue undergoes repair.
3) Finally there is an interstitial fibrosis making the “honeycomb lung”.
Diffuse ILD is usually caused by:
1) Occupational or environmental inflations causing pneumoconiosis (occupational inhalation pneumonia) such as CWP or silicosis.
2) Drugs and toxins
3) Infections, often viral like CMV and influenza
4) Others like sarcoidosis, collagen disorders, rheumatoid arthritis, SLE and idiopathic causes.
CWP has the following forms:
1) Anthracosis which is harmless but most common. The lungs appear black (like if you live in NY) but usually there is nothing that causes these patients to present.
2) Simple CWP has aggregation of coal-dust filled macrophages but they do not have significant dysfunction. They may present but this does not cause enough impairment to consider them disabled.
3) Progressive massive fibrosis or complicated CWP has serious scaring and accumulation. It leads to respiratory insufficiency.
In general upper lobes are affected more than lower lobes.
Inhalation of silica activated macrophages and releases fibrogenic factors. Lesions start as small fibrotic nodules in the upper lung and become diffuse Once silicosis gets started it continues spontaneously even if you remove the source of silica exposure. It does not have inflammation but does generate a fibrous scar and will eventually lead to cor pulmonale.
Asbestos is a family of fibrous silicates. Most are engulfed my macrophages (but still sit there for the rest of your life) but when you get too many they deposit and cause fibrosis by causing macrophages to release specific cytokines. Even exposure for a short time (6 weeks) can cause severe diffuse interstitial lung disease.
People who smoke and have asbestos exposure have a vary high chance (55x) of developing lung cancer. Asbestosis tents to cause mesotheliomas which are very malignant neoplasms of the pleura that ensheath the lung. Mesotheliomas can be sarcomatoid where they grow in a non-distinctive sheath, epithelial where they grow in patches like adenocarcinoma or biphasic (like most of them) and resemble both of the above types.
Asbestos appears in two forms:
1) Serpintine which is flexible, more common and not as pathogenic.
2) Amphibole which is straight, stiff and more pathogenic.
Ferruginous bodies it the term that is used to refer to asbestos bodies in the lungs.
Idiopathic interstitial pulmonary fibrosis is a disease of unknown etiology showing immune complexes with an unknown antigen and pulmonary fibrosis in middle aged men. Stages include:
1) Early stages show interstitial edema with alveolar macrophages and inflammation.
2) Intermediate stages include interstitial fibrosis.
3) End stage has honeycomb lung lined by type-II pnemunocytes.
Clinically this picture leads to respiratory insufficiency and ultimately cor pulmonale.
On a side note tri-chrome stain is used to stain for collagen. It will appear blue-green. The lungs should only have a little bit but you may see more when dealing with these interstitial lung diseases.
Sarcoidosis is a multisystem disease of unknown cause that causes non-caseating granulomas in may organs/tissues. Lung involvement is the most common but it often presents because of lesions on the eyes or skin.
Clinically patients present with B-symptoms (fever, night-sweats, weight loss) like you also see in Hodgkin’s lymphomas.
There are a few syndromes that can be classified as diffuse pulmonary hemorrhagic syndromes that include:
1) Goodpasture’s syndrome which is a disease affecting both the lungs and the kidneys. It messes up the basement membranes and therefore includes a combination of rapidly progressing glomerulonephritis and hemorrhagic interstitial pneumonitis.
2) Idiopathic pulmonary hemosiderosis involves the development of pulmonary edema and coughing up blood for unknown reasons.
3) Vasculitis-associated hemorrhages can affect the lungs like Wegner’s granulomatosis and SLE.
This is the condition for the person that gets asthma in a certain setting or is allergic to a specific place. The microorganisms grow in a specific set of conditions. Some types include:
1) Damp hay that causes actinomyces leading to farmer’s lung.
2) Pigeon breeders lung.
3) Air-conditioner lung.
Pulmonary alveolar proteinosis is a disease where toxic fumes irritate the alveoli and cause the production of a surfactant-like material but it does not have the anti-surface tension of surfactant. It is treated by bronchiopulmonary wash.
Bronchogenic carcinoma accounts for about 95% of primary lung cancer. It’s a cause of bronchial epithelial origen. Smoking is the BIG risk factor. These tumors are on the decline in men but on the increase in women, probably due to a similar trend in smoking habits. Types of bronchiogenic carcinoma include:
1) Squamous cell carcinomas are the most common type and are caused by smoking. They grow centrally in a major bronchus and eventually obstruct it.
2) Adenocarcinoma is the type that is most common below age 40, is seen in females and in non-smokers. The exception to all the rules. They grow in a gland-like form in central/main bronchial areas.
3) Small cell undifferentiated carcinoma is one that spreads quickly and metastases early. Like the others they form centrally and are caused by smoking. They are the worst kind.
4) Large cell undifferentiated are hard to identify and are more or less what is not part of one of the other three categories.
In the adenocarcinoma the nucli are “oat-shaped” hence the name. Lung tumors have a tendency to metastasize to the brain. Often they are first detected in the brain if they metastasize early like small cell undifferentiated carcinoma tends to do.
Prognosis is poor and 5 year survival is low. Resection offers some hope if it’s still a localized lesion but that is often not the case.
Clinical symptoms are based on what the tumor is pressing against. It may mess with the parathyroid and cause hypercalcemia or Cushing’s syndrome (elevated ACTH), a form of myasthenia/peripheral neuropathy, Horner’s syndromes (tosis, myosis, anhydrosis – loss of parasympathetic innervation).
Bronchioloalveolar carcinoma is a rare form of adenocarcinoma arising in the lung periphery from alveolar cells (type II’s, goblet cells). You see the tumors lining up alongside of the alveolar septa.
This is a rare low grade neuroendocrine tumor that usually does not show local invasion or metastases. It has positive staining for neron-specific enolase and seretonin. That is what dives it away.
1) Secondary tumors are the most common type of lung tumors.
2) Hamartomas. If they are found in adulthood they are often mistaken for true neoplasms.
3) Low grade carcinomas (benign).
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