PNEUMONIA

Bronchopneumonia

1. This refers to a patchy consolidation often through more than one lobe and frequently bilateral. 2. Virtually any lung pathogen can produce this pattern but it is usually bacterial. The most common include S. aureus, Streptococcous, Haemophilus as well as Pneumococcus. 3. This is a very common pattern seen at autopsy and is a frequent terminal event in many debilitated and chronically ill patients. 4. It grossly looks like small 3-4 cm gray-red areas scattered through out the lung parenchyma often in the most dependent portions of the lungs. 5. Microscopically it is seen as a pmn rich exudate that fills bronchi and bronchioles and then extends into the adjacent alveoli. Productive sputum

Lobar pneumonia

1. This refers to consolidation of most or all of an entire lobe of lung. 2. Pneumococcus (Streptococcus pneumoniae) is responsible for 90-95% of these cases. Rarely S. aureus, Klebsiella or Haemophilus influenzae may produce this. Antibiotic resistant Pseudomonas or Proteus may also rarely produce this pattern. 3. Four classic stages are described but rarely occur due to effective antibiotic therapy. a. Congestion- red and boggy lung. b. Red hepatization- alveoli are now filled with rbc's and pmn's giving the gross lung a red airless appearance grossly similar to liver, hence the term "hepatization". c. Gray hepatization- alveoli are still filled and airless but the rbc's have lysed so the red gross color is gone. The gray color is due to the persistence of the pmn's and fibrin filling the alveoli. d. Resolution- the alveolar exudate has been broken down. productive sputum

Complications of Pneumonia

1.Lung abscess- are cavities greater than 2 cm in diameter due to local tissue destruction, particularly with anaerobes, type 3 Pneumococcus, Staph Aureus or Klebsiella. Necrotizing pneumonia is a similar process but often involves multiple smaller cavities less than 2 cm's in size. 2. Empyema- is secondary involvement of the pleural space with purulent exudate from adjacent lung. 3. Organization- subsequent fibrous organization of the alveolar exudate can convert a portion of lung into solid airless tissue. 4. Bacteremia- spread within the blood stream may involve the heart with endocarditis, CNS with meningitis, joints with suppurative arthritis etc.

Interstitial pneumonitis

1.This refers to inflammation that is primarily confined to the interstitial space with the Alveolar space being free of inflammation. The alveolar space often contains a protienacous fluid. 2. The most common cause is Mycoplasma pneumoniae. Other causes of this pattern include viruses such as Influenza A and B, Respiratory Syncytial Virus (RSV) and Adenovirus as well as Chlamydia and Coxiella burnetti (Q fever). In some cases the etiologic agent cannot be identified. 3. Grossly no evidence of consolidation is encountered. 4. Microscopic exam shows a mononuclear cell infiltrate of lymphocytes, monocytes and occasional plasma cells confined to the interstitum. If a pmn infiltrate is seen in the alveoli then a secondary bacterial infection has likely occurred.

Mycoplasma pneumonia

Community Acquired It is transmitted via respiratory droplets. It may produce only a mild upper respiratory infection or it may produce a moderate to fatal lower respiratory infection. Clinical features -This is a process that is most common in young adults. Since the inflammation is primarily interstitial: cough is DRY - An antibody produced against Mycoplasma also cross reacts with RBC's by causing them to agglutinate at 4 degrees C, these antibodies are called cold-agglutinins and an elevation greater than 1:256 is classically associated with Mycoplasma. -Also helpful to confirm the diagnosis is a rise in antibodies that are directed against specific components of the mycoplasma organism.

Legionnaires' Disease

Community Acquired Pathogenesis - This gram negative bacteria is acquired through the inhalation of infected respiratory droplets. -Within the alveoli they are phagocytosed by alveolar macrophages but they block phagosomal fusion with the lysosome and prevent a respiratory burst. -They can then rupture the macrophage and produce widespread infection especially in an impaired host. Clinical features -Patients often have a history of recent travel. In healthy adults with intact immunity legionella pneumophila usually produces a mild transient febrile illness known as pontiac fever. -In smokers, patients with chronic lung disease or the immunocompromised the severe often fatal legionnaires disease occurs. -The diagnosis can be confirmed by detecting bacterial antigen in urine, culture, DNA hybridization or rising antibody titers.

Community-acquired MRSA pneumonia

Community Acquired Pathogenesis- Distinct from Hospital acquired MRSA in that it is more often seen as virulent skin and soft tissue infections and necrotizing pneumonia in younger patients. Gross pathology- Either lobular or lobar consolidation but may show bilateral involvement with necrosis and abscess formation. Histology- Since this is bacterial process there is a heavy pmn infiltration and if abscess formation has occurred then tissue destruction is noted. Clinical features- Any patient presenting with a community acquired bilateral pneumonia with suspicion of necrosis should initially be treated as if they have a CO-MRSA pneumonia. Confirm by culture.

Anaerobic pneumonia

Community Acquired Etiology- Bacteroides spp., fusobacteria, Actinomyces spp., microaerophilic cocci. Pathogenesis - Frequently occur in combination with aerobic oral flora such as strep viridans. This type of pneumonia is often seen in patients with periodontal disease and who are prone to aspirate such as alcoholics. Clinical features -Can be seen either in a community acquired or hospital acquired setting. and aspiration as HIGH fever, cough and infiltrate on CXR. It can often progress to copious amounts of putrid sputum, tissue necrosis within the lung with lung abscess formation or necrotizing pneumonia. Edentulous patients, who have lower numbers of oral anaerobes are less likely to develop pneumonia due to anaerobes. Confirm by culture.

Pneumococcal pneumonia

Community Acquired Etiology- Streptococcus pneumoniae types 1, 2, 3 and 7. Type 3 is particularly virulent. This organism is responsible for two thirds of all bacterial pneumonias and 90% of "lobular" community acquired pneumonias. Pathogenesis -The organism is aspirated from the oropharynx. -It is encapsulated and this capsule allows it to evade phagocytosis and via the pores of kohn it can quickly involve a large segment of lung tissue. -It stimulates a brisk pmn response that quickly floods the alveolar spaces resulting in consolidation of lung tissue and the clinical presentation of a "typical" pneumonia described above. Clinical features- This is classic example of a "typical pneumonia" listed above. Confirm by culture.

Haemophilus influenzae pneumonia

Community Acquired Pathogenesis- -It is transmitted between individuals via respiratory droplets where it may colonize the oropharynx and subsequently be aspirated. -The organism can produce a massive laryngotracheobronchitis as it descends the respiratory tree which can result in a plugging of the bronchi and smaller airways with a fibrinopurulent exudate which can be fatal. Clinical features -This is a process that is most often seen in young children. This is a pediatric EMERGENCY and has a high mortality rate. -One of the biggest clinical clues that you are possibly dealing with this organism is toxic ill appearing child between 6 months and 5 years of age with clinical signs of pneumonia. -It is also seen in COPD patients with pneumonia. Confirm by culture.

Chlamydial pneumonia

Community Acquired The mode of transmission is not entirely clear. Infected aerosols may be important in the transfer of infection from person to person. It produces a patchy atypical pneumonia type of illness. Clinical features -Most common in those 65-79 years old. -This pneumonia is usually mild with fever, cough and crackles. -CXR can range from small patchy involvement to consolidation of an entire lobe. -Diagnosis is based on isolation of the organism or serologic evidence of acute infection or both. A four-fold rise in IgG or IgM or IgM > 1/16 or IgG > 1/512. Note: A severe form of pneumonia called ornithosis is caused by another type of chlamydia organism-Chlamydia psittaci. -usually pharyngitis followed in 1-3 weeks by pneumonia

Viral pneumonia

Community Acquired These viruses are acquired via infected respiratory droplets. The Influenza virus can infect ciliated bronchial epithelial cells damaging the ciliary escalator and making the patient prone to bacterial superinfection. This is often seen in fatal cases. Fever, headache and myalgias may be the dominant symptoms. A cough if present is often dry since the inflammation is interstitial instead of intraalveolar. Diagnosis can often be made via viral culture or smears made from nasopharygeal swabs. H1N1 (swine flu) is unique in that it can be fatal in a much younger patient population and can kill on it's own without needing a bacterial superinfection.

CMV pneumonia Morphology

Gross pathology- Patchy or diffuse involvement may be seen. d. Histology- Classic intranuclear inclusions may be seen in the nuclei of alveolar lining cells, macrophages or endothelial cells. Due to the immunosuppresion minimal interstitial inflammation may be seen. The alveoli often have a proteinacous fluid within them and focal hyaline membranes may form.

Pneumococcal pneumonia Morphology

Gross pathology- This is the classic example of a lobar pneumonia previously described with the 4 stages of congestion, red hepatization, gray hepatization and resolution. Histology - depending upon the stage one would expect to see intraalveolar pmn's and possibly either intact RBC's or fibrin.

Staphylococcal pneumonia

Hospital Acquired These gram-positive cocci very often colonize the oropharynx of hospitalized patients and as such may be aspirated. This organism is also common agent to secondarily involve the lung during a bacteremia such as in i.v. drug abusers or patients with Staphylococcal infections elsewhere in the body common cause of lung abscess formation. In a chronically ill hospitalized patient this infection can be very insidious in it's presentation with only fever, tachycardia and increased respiratory rate being seen while the classic lung findings of pneumonia are often absent. A few scattered rales may be heard. The reason this can often be subtle is because if it is acquired via a hematogenous route then the Infiltrate will start in the interstitium and then progress to a alveolar infiltrate. Confirm by culture.

Enteric gram-negative bacilli pneumonia

Hospital Acquired These organisms often colonize the oropharynx of hospitalized patients and as such may be aspirated. Klebsiella pneumoniae is especially notorious for hospital-acquired pneumonia and produces a large antiphagocytic capsule that is partially responsible for it's virulence. The development of high fever or abnormally low body temperature with cough productive of purulent sputum The clinical manifestations can be modified by dehydration which may make rales or chest x-ray changes in apparent until the patient is hydrated and immunosuppressed patients may not mount a significant immune response. Diagnosis is often possible via sputum gram-stain and culture.

Pseudomonas pneumonia

Hospital Acquired account for over 50% of hospital- acquired pneumonia. It often colonizes respiratory therapy equipment, it can grow in distilled water and other fluids and as such is easily acquired especially in intubated or chronically hospitalized patients. It often colonizes the hospitalized patient's oropharynx where it is easily aspirated. This organism produces numerous virulence factors including elastase which degrades Immunoglobulins and may be important in tissue invasion as well as phospholipase which degrades surfactant. These patients can develop fever, dyspnea and patchy infiltration on chest x-ray. Diagnosis is usually confirmed by sputum culture.

CMV pneumonia

In neonates or immunosupressed patients a severe multiorgan necrosis can occur which is often fatal. In HIV patients this infection within the lungs very commonly coexists with Pneumocystis carinii pneumonia which usually overshadows it clinically. In contrast in patients who have undergone allogeneic bone marrow transplantation a CMV pneumonia almost never has a coexistent Pneumocytis pneumonia. CMV can be confirmed by seeing the characteristic inclusions on bronchoalveolar lavage (BAL) and while this is very specific it is not extremely sensitive. The sensitivity is greatly improved with the use of viral cultures on the BAL obtained specimen.

Histoplasmosis pneumonia

It attaches to integrin receptors on the surface of macrophages, multiplies in the phagolysosome and then lyses the macrophage where it is free to infect other macrophages. In immunocompetent hosts this process can be held in check with granulomatous inflammation much like TB. In immunocompromised patients these organisms may grow wildly and result in overwhelming pulmonary infection as well as a disseminated multiorgan destruction. In the immunocompetent this infection is usually asymptomatic or mild in nature. In the immunosupressed it can present much like miliary TB with fever, weight loss and night sweats. Massive involvement of the lung parenchyma may result in pulmonary failure or systemic involvement can produce liver failure, bone marrow failure etc. Diagnosis can be achieved by culture of the organism from the sputum or blood in disseminated cases or demonstrating the yeast in tissue. Serology has a low sensitivity and specificity especially in immunosuppressed.

Pneumocystis pneumonia

It attaches to the alveolar lining cells where it proliferates and fills the alveolar spaces with organisms and cell debris thus compromising respiratory function. This is often the first diagnosed opportunistic infection in patients with HIV. It is also the most common cause of death in these patients. It may present in a patient who is not known to have HIV as a patchy pneumonia that fails to clear as an outpatient with antibiotics. History of risk factors for HIV can establish a suspicion of Pneumocystis which can be confirmed via bronchoalveolar lavage with silver stain to look for the organisms. also malnourished children

Atypical pneumonia

The term "atypical" comes from the fact that this type of pneumonia is slower in onset, physical exam shows only scattered rales with out signs of consolidation and since the inflammation is usually interstitial and not intraalveolar the cough is usually dry and does not produce sputum. The classic example of an atypical pneumonia is Mycoplasma pneumoniae. Legionella and Chlamydia pneumonia are also considered atypical pneumonias.

Typical pneumonia

This is the classic presentation of pneumonia with sudden onset of fever, chills, physical exam findings of consolidation (dullness to percussion, etc.) and chest x-ray findings. Since these patients have an intraalveolar exudate they typically have a cough productive of purulent sputum. The classic example of a typical pneumonia is Pneumococcal pneumonia.

Immunocompromised Pneumonia Caveats

a. Bacterial lower respiratory infections caused by the usual organisms are one of the most severe pulmonary disorders in HIV patients MD 823 b. Some pulmonary infiltrates in HIV patients are actually malignant such as Kaposi's sarcoma c. The CD4+ T-cell count can give a big clue as to the organism: Counts >200=Bacterial or TB, counts between 50-200=CMV and counts <50 often =Pneumocystis

Histoplasmosis pneumonia Morphology

c. Gross pathology- Focally granulomatous like TB or diffusely airless in the immunocompromised. d. Histology- In the immunocompetent well formed epithelioid granulomas very similar to TB are seen while in the immunocompromised these granulomas are not formed. Instead there are foci histiocytes that are stuffed with these small 2-5 micron organisms that are seen with a silver stain

Legionnaires' Disease. Morphology

c. Gross pathology- In the overwhelming fatal cases the lung shows patchy consolidation that can progress to involve entire lobes. d. Histology- This can produce an intraalveolar infiltrate with a higher ratio of mononuclear cells to pmn's. Due to the above described lysis of macrophages focal areas of necrotic macrophages are seen surrounding areas of intact monocytes and pmn's. If a silver stain is then used the microbes are massive in these necrotic areas as would be expected.

Pneumocystis pneumonia Morphology

c. Gross pathology- Infection with this organism can result in patchy or diffuse lung involvement with the lungs being airless and beefy red. d. Histology- The alveolar spaces are filled with proliferating organisms and cellular debris which has a foamy appearance. Hyaline membranes may occasionally be seen. A mild interstial infiltrate is seen but due to the immunocompromised status it is minimal for the degree of infection. A co- existent infection (often CMV) is also commonly observed.

Viral pneumonia Morphology

c. Gross pathology- Similar to mycoplasma pneumonia with either a patchy or diffuse congested lung without gross consolidation. d. Histology- Similar to mycoplasma pneumonia with an interstitial pneumonitis consistent of lymphocytes, monocytes and occasional plasma cells. If a bacterial superinfection has occurred as described above then the histology may look identical to bacterial lobar or bronchial pneumonia.

Mycoplasma pneumonia morphology

c. Gross pathology- Since the mild upper and lower tract infections are rarely fatal the gross pathology is usually only seen in the severe fatal cases. In these cases the lungs are congested but lack the consolidation seen in lobar pneumonia. d. Histology- This is the classic example of Interstitial pneumonitis. The alveolar septa are widened by a mononuclear infiltration within the interstitium. Some severe cases may progress to damage the alveoli to the point that hyaline membranes form resulting in an adult respiratory distress syndrome.

Pseudomonas pneumonia

c. Gross pathology- The pattern is usually that of a bronchopneumonia but in the severe cases entire lobes may be involved. There is prototypically a necrotizing inflammation in a "fleur-de-lis" with white necrotic centers surrounded by a red hemorrhagic peripheral zone. d. Histology- A neutrophil rich exudate filling the bronchi and bronchioles and spilling out into the surrounding alveoli.

Chlamydial pneumonia Morphology

c. Gross pathology- This is highly variable and can range from patchy bilateral consolidation to focal consolidation of an entire lobe depending of the severity of the infection. d. Histology- Interstitial collections of lymphocytes and histiocytes similar to other atypical pneumonias.

Anaerobic pneumonia Morphology

c. Gross pathology- Typical bacterial pneumonia with bronchopneumonia pattern or rarely lobar. True abscesses can form or smaller (< 2 cm) areas of necrotizing pneumonia may be present. d. Histology- Since this is bacterial process there is a heavy pmn infiltration and if abscess formation has occurred then tissue destruction is noted.

Haemophilus influenzae pneumonia Morphology

c. Gross pathology- usually shows patchy areas of consolidation (bronchopneumonia) but may also show a lobar pattern. d. Histology- Intraalveolar pmn's either in a bronchopneumonia pattern or throughout an entire lobe.

Staphylococcal pneumonia Morphology

c. Gross pathology-A bronchopneumonia pattern is often seen but a lobar pattern may also be seen as well as focal abscess formation. d. Histology- A neutrophil rich exudate either scattered in a patchy distribution or diffuse. If abscess formation has occurred then focal destruction of lung parenchyma with sheets of pmn's is seen.

Enteric gram-negative bacilli pneumonia Morphology

d. Histology- A rich neutrophil rich exudate either scattered in a patchy distribution or diffuse is seen. If abscesses have formed then focal destruction of lung parenchyma with sheets of pmn's and tissue debris will be observed.

Procalcitonin

has been studied to facilitate the decision of whether to use antibiotics in patients with pneumonia. It can help to distinguish between bacterial and viral pneumonia, reduce antibiotic use, predict severity of the pneumonia based on the magnitude of the result and may predict survival increased = bacterial