PATHOLOGY OF ACUTE/SUBACUTE PULMONARY INFECTIONS

Question 1

Alterations in normal host defenses can lead to?

Answer 1

x Accumulation of secretions (see leftimagebelow)–can occur with overproduction, cystic fibrosis, bronchial obstruction, etc. x Loss/suppression of cough reflex –for any diverse reason and can lead to aspirationof gastric contents x Suppression of mucociliary apparatus –either due to impairment of function (immotile ciliasyndrome, etc.) or destruction of ciliated epithelium (metaplasia, etc.) x Impaired alveolar macrophage ability –can lose their bactericidal and/or phagocytic function when exposed to various toxins x Pulmonary congestion or edema

Question 2

Community acquired pneumonia infections? what is it? symptoms? From a pathology perspective what are the patterns of this disease?

Answer 2

These infections are acquired by healthy people in the normal environment (community), sometimes as a secondary infection following an upper respiratory tract infection. These patients typically present with abrupt signs and symptoms (acutely): x High fever and shaking chills x Pleuritis and chest pain x Purulent sputum, possibly hemoptysis (‘rusty’ colored sputum) x Elevated acute phase reactants (C-reactive protein and procalcitonin in bacterial infxns) x Mortality up to 10% in those requiring hospitalization Determining (by culture or other) the causative agent and the extent of disease is paramount, as it guides appropriate therapy. From a pathology perspective, two broad patternsof disease can be mechanistically described (and are oftenoverlapping in any patient): Lobar pneumonia Bronchopneumonia

Question 3

explain lobar pneumonia?

Answer 3

x Organisms and inflammation spread through pores of Kohn(interalveolar connections)

x Neutrophils fill alveoli and solidify a large region or whole lobe (consolidation)

x Consolidated lung is heavyand solid feeling, and takes on the gross appearance of liver (so-called hepatization):

o Red hepatizationis earlier and consists of pus, neutrophils, edema, red cells/congestion, and some fibrin

o Grey hepatizationis later and consists of breaking down red cells, more macrophages, more fibrin, and some fibroblasts ready to create fibrosis potentially

Question 4

Inflammation organisms fluid fibrin etc can travel through______? to consolidate the lung?

Answer 4

Inflammation, organisms, fluid, fibrin, etc., can travel through pores of Kohn(left image at arrow) and eventually will consolidate entire regions of lung; right image showing theabrupt cutoff between consolidated and non-consolidated regions. All of these images on this page would appear as predominately red hepatization

Question 5

Explain brochopneumonia?

Answer 5

x Organisms and inflammation spreads along airways(bronchioles and bronchi)

x Neutrophils fill airways and then extend into adjacent alveoli (patchy consolidation)

x Involved areas may coalesce and appear like a lobar pneumonia

x May be a pattern seen with viral etiologies or aspiration

Question 6

explain Legionella pneumophilia?

Answer 6

Question 7

What is Community acquired acute/subacute “atypical” pneumonia?

Answer 7

This category needs to be fully explained. It is a diverse group of organisms that share some common (albeit vague) features:

x Usually non-abrupt clinical course (less productive sputum, SOB, etc.) and higher likelihood of generalized symptoms (headache, sweating, myalgias, etc.)

x Often viral in etiology (influenza A/B, respiratory syncytial virus, rhinovirus, adenovirus, human metapneumovirus, etc.)or ‘unusual,’less virulent bacteria (Mycoplasma, Chlamydia)

x Causative organisms may be more difficult to identify in a laboratory setting

x Range from self-limited and mild (many upper and lower viral infections) to severe epidemics (influenza)

The ‘atypical’ pneumonias are also sometimes referred to ‘walking’ pneumonias, although both terms should probably be used as infrequently as possible.

Question 8

In community acquired atypical pneumonia the lungs grossly appear? Microscopically?

Answer 8

Grossly, affected lungs will appear reddish and congested. As the pneumonia evolves, foci of bronchopneumonia are possible.

Microscopically, the following are most likely seen:

x prominent/predominate interstitial (within alveolar septae) inflammatory reaction

x Expansion of septae with lymphocytesand macrophages (few PMN’s)

x Septae may contain fibrin which evolves into fibrosis (see arrow in image)

Question 9

Explain SARS?

Answer 9

severe acute respiratory syndrome (SARS) coronavirus

Signs and symptoms in the 2002-2003 outbreak included a typical upper respiratory tract infection and fever, a variety of constitutional symptoms, followed sometime later by a lower respiratory tract infection that resembled influenza virus.

x A new coronavirus was identified (SARS-CoV)

x Mortality of 9.6% was due primarily to respiratory distress/failure

x Since 2004 the virus has disappeared (has not yet been identified again)

Question 10

What are the outcomes/complicationsof acute pneumonia? more common with?

Answer 10

Outcomes/Complications of acute pneumonia(more common with bacterial etiologies)

1) Resolution–any exudate is degraded (by macrophages) and lung architecture restored
2) Organization–inflammatory process may progress through grey hepatization and eventuate in some degree of fibrosis
3) Pleural involvement–pleuritis (inflammation of pleura) or empyema (a gross of collection of pleural space-located pus) are possible x May lead to extensive scarring
4) Necrotization–intrapulmonary abscess formation and/or cavitation (see below)

Left Image: grey hepatization micro -mix of cell types and pinkish fibrin Middle image: intraalveolar debris is largely necrotic and septae begin to become more visible Right image: septae are widened and contain ‘plugs’ of fibrosis (at arrow)

Question 11

What does this image show?

Answer 11

Image: Lung isbeingpushed to the right side of the image here (thin arrow), due to a huge collection of thick greenish pus in the pleural cavity, an empyema(thick arrow). This pus is drying out, becoming more solidified (a loculated empyema), and will likely require surgical intervention to fully remove it, assuming the patient survives the acute pneumonia.

Question 12

Explain necrotizing cavitary and abscess forming pneumonias?

Answer 12

Necrotizing, cavitary and abscess-forming pneumonias

This clinical process is characterized by some combination of cough, fever, chest pain, and often a large volume of purulent or bloody sputum. Clubbing (see image) of the fingers and toes can also occur after a few weeks. Multiple small (<2cm) abscesses can develop and we call those necrotizing pneumonias, otherwise larger lesions are called abscesses. Mortality can be up to 20% in higher risk populations. Causes are diverse:

x Preceding primary lung infection (see above)

x Aspiration of infective material (very common, see below)

x Neoplasm, often causing obstruction of an airway leading to secondary infection

x Septic embolism to the lung

x Traumatic implantation of infective material

x Infection spreading to the lung from adjacent infection of esophagus, pleural cavity, etc

Question 13

As the abscess evolve they can what?

Answer 13

As the abscess(es) evolve, they can overtake more areas of lung tissue, and the eventually cavitate (see image at right)

x Oxygen changes within the cavity can allow continued microbial growth

x Antibiotic penetration in and around theabscess/cavitation may be impaired

Question 14

Organisms in abscess are usually?

Answer 14

Organisms in an abscess are often either only anaerobes(about half the time) or are mixed anaerobes-aerobes(about half the time). Identification is often complicated, and treatment may be undertaken without absolute surety about the causative organism(s).

x Aerobes –K. pneumonia, S. aureus, S. pyogenes

x Anaerobes –oral flora including Fusobacterium, Bacteriodes, Prevotella, Peptococcus/Peptostreprococcus (gram-positive anaerobic cocci or coccobacilli) species

Question 15

What is aspiration pneumonia? What are the underlying abnormalities?

Answer 15

Aspiration is usually seen in patients with debilitation, dementia, unconsciousness(like following stroke), or in those with repeated vomiting(like alcoholic abuse). Underlying mechanistic abnormalities are those of impaired cough or gag reflexesleading to aspiration:

x partly chemical in that gastric contents are acidic, leading to increased tissue destruction

x partly bacterial in that oral (oropharyngeal) contents contain a high level of mixed bacteria

Question 16

Aspiration pneumonias are typically? Causing flora?

Answer 16

These pneumonias are typically necrotizing and abscess-forming, the latter becoming more pronounced if the patient survives the acute onset on pneumonia. Aspiration pneumonia is a common cause of disease that pushes a patient (possibly with underlying disease) into organ failure, which then taxes other organ systems leading to multisystem organ failure and death.

x Causes are anaerobic oral flora(see above in Necrotizing category) or ‘colonizing’ aerobes: H. influenza, S. pneumonaie, P. aeruginosa, S. aureus

Question 17

In general the identification of anerobes can be difficult why?

Answer 17

In general the identification of anaerobes can be more difficult for several reasons:

x Mixed organisms so isolation is harder

x Gram stain can be weak or inconsistent

x Limiting oxygen with special apparatuses is harder than not

Question 18

Explain healthcare associated/hospital associated pneumonia?

Answer 18

Health care-associated/Hospital-acquired pneumonia Generally defined as anything acquired from health care setting. Many of these have been talked about before:

x Gram-positive cocci (S. aureus and S.pneumoniae)

x Gram-negative rods (K. pneumoniae and other Enterobacteriaceae, P. aeruginosa) T

hese are most problematic due to their bacterial resistances to antibiotics, such as methicillinresistant S. aureus, the growing problem of gram-negative resistances, etc.