The “space” between the endothelium and the type-1 pneumocyte, is the blood air interface
Viral pneumonias, generally interstitial, bacterial pneumonias generally alveolar!!!
Corona viruses are RNA, “enveloped”, i.e., “crowned” viruses
“Chronic” by classification, but “granulomatous” by histology.
11respiratory system (2) pathology
Trachea divides into right and left mainstem bronchi.
Each main bronchus divides into lobar bronchi, then into
Lobar bronchi are usually called secondary bronchi and
segmental bronchi are called tertiary bronchi.
Bronchioles lack cartilage and submucosal glands
Right bronchus more vertical than left, thus aspirated material
tends to enter right lung
Lung has double arterial supply - pulmonary and bronchial
Alveolar capillary basement membrane fuses with alveolar epithelium to
form a single membrane for oxygen and carbon dioxide diffusion.
Acinus contains 3-5 terminal bronchioles, alveolar ducts and alveoli
Alveoli are lined by pseudostratified, columnar epithelium
Alveoli contain type I and II pneumocytes
Type I pneumocytes: 95%, flattened
Type II pneumocytes: 5%, produce surfactant, involved in repair if type I
Bronchial-bronchiolar epithelium contains goblet cells, neuroendocrine
(Kultschitsky’s) cells, serous cells, basal cells, Clara cells and ciliated
infections in the form of pneumonia are
one of the leading causes of death all around the
is due to
(1) the epithelial surfaces of the lung are constantly
exposed to liters of variously contaminated air
(2) nasopharyngeal flora are regularly aspirated
during sleep, even by healthy persons; and
(3) other common lung diseases render the lung
parenchyma vulnerable to virulent organisms.
Broadly defined as any infection in the lung
may present as acute, fulminant clinical disease
or as chronic disease.
: Inflammation caused by organisms.
histologic spectrum of pneumonia may vary
Fibrinopurulent alveolar exudate seen in
acute bacterial pneumonias.
Mononuclear interstitial infiltrates in viral
and other atypical pneumonias.
Granulomas and cavitation seen in many of
the chronic pneumonias.
Acute bacterial pneumonias can present as one
of two anatomic and radiographic patterns,
- Bronchopneumonia and
- Lobar pneumonia.
Aetiological or according to clinical setting
Community-Acquired Acute Pneumonia
Community-Acquired Atypical Pneumonia
Necrotizing Pneumonia and Lung Abscess
Pneumonia in the Immunocompromised Host
Community-acquired acute pneumonias are bacterial in
Onset is usually abrupt, with high fever, shaking chills,
pleuritic chest pain, and a productive mucopurulent cough;
occasional patients may have haemoptysis.
S. pneumoniae (or pneumococcus) is the most common
cause of community-acquired acute pneumonia.
Caused by Streptococcus pneumoniae
Is responsible for more than 90% of lobar
Can present as
In lobar pneumonia the contiguous
airspaces of part or all of a lobe are
homogeneously filled with an exudate
that can be visualized on radiographs
as a lobar or segmental consolidation.
Implies a patchy distribution of
inflammation that generally involves more
than one lobe.
This pattern results from an initial infection
of the bronchi and bronchioles with
extension into the adjacent alveoli.
– Inflammation involves a lobe diffusely.
4 pathological stages identified in the progress
of untreated infection.
Stage I- Acute congestion
2. Stage II- Red hepatization
3. Stage III- Gray hepatization
4. Stage IV- Resolution
Lasts for 1-2 days
Acute congestion and oedema
Lung is heavy and firm
Abundant frothy red fluid can be squeezed from it
Alveolar spaces filled with inflammatory exudates and
Neutrophils are abundant
Fibrin will be present
Gram stained smear show large number of gram positive
for 2-4 days
Pleural surface have fibrinous tags of fibrin.
Cut surface appear dry, firm red granules , feel like
liver ( liver-like consistency).
Affected lung tissue airless and sink in water.
Capillary engorgement persists.
Alveolar spaces are packed with neutrophils, red
cells, and fibrin
Organisms are almost disappeared, if present
Lasts for 4-8 days
– Cut surface is dry, granules and gray.
– Fibrinosuppurative exudate persist within the alveoli.
– Capillary engorgement resolved
– Alveolar spaces are distended and filled with dense fibrin
and with dead and dying polymorphs.
– Occasional degenerating red cells are seen.
Fibrinous or fibrinopurulent pleuritis (pleural
exudate) may resolve or undergo organization,
leaving fibrous thickening or permanent adhesions.
Lung parenchyma appear normal
Transformation of exudates to
mucoid masses richly
infiltrated by macrophages
Capillaries will be normal
Alveolar space will have macrophages. Exudates within
the alveoli are enzymatically digested to produce
granular, semifluid debris that is resorbed, ingested by
macrophages, coughed up, or organized by fibroblasts
growing into it.
seen among infancy, old age ,
patients with debilitating diseases and
patients with prolonged bed rest.
colonize the bronchiole and
extend through the walls into surrounding
Foci of inflammatory consolidation are distributed in patches
throughout one or several lobes, most frequently bilateral
Well-developed lesions up to 3 or 4 cm in diameter are
slightly elevated and are gray-red to yellow .
The lung substance immediately surrounding areas of
consolidation is usually hyperemic and edematous.
Confluence of these foci may occur in severe cases,
producing the appearance of a lobar consolidation.
involvement is less common than in
The reaction consists of focal suppurative exudate that fills
the bronchi, bronchioles, and adjacent alveolar spaces.
Ciliated epithelium is destroyed.
High grade fever, and productive cough.
(Interleukin (IL) 1 and tumor necrosis factor (TNF),
results in fever. IL-8 and granulocyte CSF, stimulate
the release of neutrophils and their attraction to the
Pleuritic pain and pleural friction rub.
The whole lobe is radiopaque in lobar pneumonia,
whereas there are focal opacities in
Complete restitution of the lung is the rule for both forms.
Complications may occur
(1) Tissue destruction and necrosis may lead to
(2) Suppurative material may accumulate in the
pleural cavity, producing an empyema;
(3) Organization of the intra-alveolar exudate may
convert areas of the lung into solid fibrous tissue;
(4) Bacteremic dissemination may lead to
meningitis, arthritis, or infective endocarditis.
Community-acquired atypical pneumonias
The term atypical denotes the moderate amount
of sputum, no physical findings of consolidation,
only moderate elevation of white cell count, and
lack of alveolar exudate.
Viruses: Influenza virus, the RSV, adenovirus,
rhinoviruses, rubeola, and varicella
Chlamydia pneumoniae; and Coxiella burnetii
All causal agents produce essentially similar
The lung involvement may be quite patchy or may
involve laterally or unilaterally.
The affected areas are congested. The pleura is
smooth, and pleuritis or pleural effusions are
alveolar septa are widened and
edematous and usually have a
mononuclear inflammatory infiltrate of
lymphocytes, macrophages, and
occasionally plasma cells.
Severe Acute Respiratory Syndrome (SARS)
SARS first appeared in November 2002 in the
Guangdong Province of China
Like most other NON-bacterial pneumonias
confirmed by PCR
Like most viral pneumonias, interstitium infiltrated,
some giant cells often present.
Pulmonary infections acquired in the course of a
They are common in patients with
– CATHETERS, VENTILATORS
– Enterobacteriaceae, pseudomonas
– staph (MRSA)
– MRSA (MR=Methicillin Resistant)
Hospital-acquired infections are serious and often
Occurs in markedly debilitated patients or
These patients have abnormal gag and swallowing
reflexes that predispose to aspiration.
The resultant pneumonia is partly chemical because of
the extremely irritating effects of the gastric
This type of pneumonia is often necrotizing.
In those who survive, Often lead to lung ABSCESSES
USUALLY NOT persistences of the community or
nosocomial bacterial infections.
Often SYNONYMOUS with the 4 classic systemic
fungal or granulomatous pulmonary infections, i.e.,
TB, Histo-, Blasto-, Coccidio-
If you see pulmonary granulomas, think of a
CHRONIC process, often years
term “pulmonary abscess” describes
a local suppurative process within the
lung, characterized by necrosis of lung
sinobronchial infections, dental sepsis,
and bronchiectasis play important roles in
Etiology and Pathogenesis
ASPIRATION of infective material
NEOPLASIA, sec. infection is common
From NEIGHBORING structures:
ANY pneumonia which is severe and
destructive, and inadequate treatment
Abscesses: a few millimeters to large cavities of
5 to 6 cm, single or multiple.
Pulmonary abscesses due to aspiration are more
common on the right and are most often single.
Abscesses that develop in the course of
pneumonia or bronchiectasis are usually
multiple, basal, and diffusely scattered.
Septic emboli and pyemic abscesses are multiple
and may affect any region of the lungs.
cardinal histologic change in all
abscesses is suppurative destruction of
the lung parenchyma within the central
area of cavitation.
chronic cases considerable fibroblastic
proliferation produces a fibrous wall.
Major cause of life-threatening acute LRT
infections, otitis media, and meningitis in young
In adults- Most common cause of acute
exacerbation of COPD in adults
Exists in two forms: encapsulated (5%) and
Cause of secondary bacterial pneumonia in
children and healthy adults following viral
MRSA, of course, is usually NOT “community”
Complications: lung abscess and empyema.
I/V drug abusers are at high risk of developing
staphylococcal pneumonia in association with
Afflicts debilitated and malnourished people,
particularly chronic alcoholics.
ALCOHOLICS with pneumonia are often thought
of as having Klebsiella until proven otherwise
Thick and gelatinous sputum is characteristic,
because the organism produces an abundant
viscid capsular polysaccharide, which the patient
may have difficulty expectorating.
OBSTRUCTIVE vs. RESTRICTIVE AIRWAY
Obstructive airway disease: increase in resistance
to airflow due to obstruction at any level; includes
emphysema, chronic bronchitis, bronchiectasis,
asthma; reduced maximal airflow rates (FEV1)
Restrictive airway disease: reduced expansion of
lung parenchyma with decrease in total lung
capacity; normal FEV1; due to chest wall disorders
(polio, obesity, pleural disease, kyphoscoliosis),
interstitial / infiltrative diseases
Common abstructive and restrictive
COPD (Chronic bronchitis+emphysema)
Idiopathic or drug induced pulmonary fibrosis
Overlap between chronic obstructive lung
Site of disease
Chronic obstructive pulmonary
Also called chronic obstructive lung disease
Two sub types: Chronic bronchitis and
emphysema, coexist to variable degree in most
Characterized by gradual decrease in FEV1 over
a period of time with a acute episode of acute
Risk factors: smoking, air pollution, respiratory
infection, positive family history
Natural progression of COPD
chronic productive cough, wheeze
50s: 1st acute chest illness
60s: Dyspnea on exertion, increasing
cough/sputum production, frequent
Late stage: Hypoxemia with cyanosis,
defined clinically as persistent
cough with sputum for at least 3 months
for at least 2 consecutive years
Tobacco smoke (90%) and dust from grain,
cotton, and silica.
Hypersecretion of mucus in the large airways,
associated with hypertrophy of the submucosal
glands in the trachea and bronchi.
Proteases released from neutrophils, and matrix
metalloproteinases, stimulate mucus
infection- producing acute
smoke interferes with ciliary
action of the respiratory epithelium, it may
cause direct damage to airway epithelium,
and it inhibits the ability of bronchial and
alveolar leukocytes to clear bacteria).
Gross: hyperemia, swelling, and edema of the
mucous membranes, frequently accompanied by
excessive mucinous or mucopurulent secretions.
Microscopic: chronic inflammation of the
airways and enlargement of the mucus-secreting
glands of the trachea and bronchi, mucous gland
Reid index: ratio of thickness of mucus gland
layer to thickness of wall between epithelium and
cartilage ( normal is 0.4), increased in chronic
The bronchial epithelium may exhibit squamous
metaplasia and dysplasia
Persistent productive cough
Dyspnea on exertion
Hypercapnia, hypoxemia, and cyanosis (“blue
CXR: Increased bronchovascular marking
Longstanding cases- leads to cor pulmonale with
Death may also result from further impairment of
respiratory function due to superimposed acute
Definition: Abnormal permanent enlargement
and destruction of air spaces distal to terminal
bronchiole without obvious fibrosis
Differs from overinflation, which is not due to
wall destruction (example: due to loss of
Acinar and airspace enlargement is usually due
to tobacco related wall destruction.
Type of emphysema
Emphysema is classified according to its
anatomic distribution within the lobule.
There are four major types:
(1) centriacinar (> 95% of cases)
(3) paraseptal (distal), and
The first two cause clinically significant airflow
Type of emphysema
Centriacinar emphysema: affects proximal
(central) part of acini, sparing distal alveoli;
worse in upper lobes, particularly apices
Seen in heavy smokers, coal worker
Clinically significant at age 40+ in smokers,
although ventilatory deficits seen earlier
Type of emphysema
Panacinar emphysema: acini uniformly
enlarged from respiratory bronchiole to terminal
alveoli; usually lower lungs; associated with
Paraseptal (distal acinar) emphysema: distal
acini affected, multiple continuous airspaces are
affected; may be source of spontaneous
Irregular emphysema: minor clinically; invariably
associated with scarring, irregular involvement
Macrophages, CD8+ and CD4+ T lymphocytes,
and neutrophils are increased in lung.
Activated inflammatory cells release a variety of
mediators, including leukotriene B4, IL-8, TNF,
that are capable of damaging lung structures or
sustaining neutrophilic inflammation.
Protease-antiprotease imbalance, aided abetted
by imbalance of oxidants and antioxidants
The protease-antiprotease imbalance hypothesis
is based on the observation that patients with a
genetic deficiency of the α1-antitrypsin have a
markedly enhanced tendency to develop
α1-antitrypsin, normally present in serum, tissue
fluids, and macrophages, is a major inhibitor of
α1-antitrypsin is encoded by codominantly
expressed genes on the proteinase inhibitor (Pi)
locus on chromosome 14.
The following sequence is postulated:
1. Neutrophils are normally sequestered in
peripheral capillaries, and a few gain access to
the alveolar spaces.
2. Any stimulus that increases either the number
neutrophils and macrophages in the lung or the
release of their protease-containing granules
increases proteolytic activity.
3. With low levels of serum α1-antitrypsin,
elastic tissue destruction is unchecked and
In smokers, neutrophils and macrophages
accumulate in alveoli.
Direct chemoattractant effects of nicotine as well
as the effects of reactive oxygen species (ROS)
contained in smoke.
These activate the transcription factor NF-κB,
which switches on genes that encode TNF and
chemokines, including IL-8. These, in turn,
attract and activate neutrophils
Accumulated neutrophils are activated and
release their granules, rich in a variety of cellular
proteases (neutrophil elastase, proteinase 3, and
cathepsin G), resulting in tissue damage.
In addition to elastase, matrix metalloproteinases
derived from macrophages and neutrophils have
a role in tissue destruction
voluminous lungs, generally, the
upper two thirds of the lungs.
Large apical blebs or bullae are more
characteristic of irregular emphysema
secondary to scarring and of distal acinar
Microscopic: abnormally large alveoli separated
by thin septa with only focal centriacinar fibrosis.
The pores of Kohn are so large that septa appear
to be floating or protrude blindly into alveolar
spaces with a club-shaped end.
Destruction of alveolar walls
With advanced disease, larger abnormal
airspaces, blebs or bullae, which often deform
and compress the respiratory bronchioles and
vasculature of the lung.
The clinical manifestations of emphysema do not
appear until at least one third of the functioning
pulmonary parenchyma is damaged.
Cough or wheezing is the chief complaint.
Barrel-shaped chest, dyspnea, sits forward in a
hunched-over position, and breathes through
Cor pulmonale and eventually CCF, related to secondary
pulmonary vascular hypertension.
Death is due to
– respiratory acidosis and coma, right-sided heart
failure, and massive collapse of the lungs secondary to
Treatment: bronchodilators, steroids, bullectomy, and, in
selected patients, lung volume reduction surgery and lung
Substitution therapy with α1-AT is being evaluated.
Asthma is a chronic but
reversible inflammatory disorder of the
airways characterized by recurrent
episodes of wheezing, breathlessness,
chest tightness, and coughing.
hallmarks of the disease are
hyperresponsiveness of airway to a
variety of stimuli, resulting in
inflammation of the bronchial walls and
increased mucus secretion
Type I IgE-mediated hypersensitivity reaction .
The disease usually begins in childhood and is
triggered by environmental allergens (dust,
pollens, animal dander and food).
A positive family history of asthma is common.
Serum radioallergosorbent tests (called RAST)
identify the presence of IgE specific for a panel
Asthma : Non-immune,
respiratory infections due to viruses (e.g.,
rhinovirus, parainfluenza virus) are
IgE-normal, no positive family history
It is thought that virus-induced
inflammation of the respiratory mucosa
lowers the threshold of the subepithelial
vagal receptors to irritants.
Aspirin-sensitive asthma occurs in individuals
with recurrent rhinitis and nasal polyps.
This form of asthma is stimulated by fumes,
organic and chemical dusts (wood, cotton,
platinum), gases (toluene), and other chemicals
(formaldehyde, penicillin products).
Pathogenesis (atopic asthma)
major etiologic factors in atopic
asthma are a genetic predisposition to
type I IgE mediated hypersensitivity reaction
Initial sensitization affects T helper 2 cells, which
release IL-4/5, which promote IgE release by B
cells, that binds to mucosal mast cells and
Reexposure to allergen leads to mediator release
from mucosal mast cells
IL-4-production of IgE, Il-5-activates locally
recruited eosinophils, IL-13-mucus secretion
(minutes): release of preformed
Late phase reaction (hours): due to
release of major basic protein from
eosinophils, which causes epithelial
damage and airway constriction.
Potent mediators: leukotrienes C4, D4, E4
(bronchoconstriction, increased vascular
permeability, increased mucus secretion) and
acetylcholine (cause airway smooth muscle
constriction by directly stimulating muscarinic
Minor mediators: histamine, prostaglandin D2
Others: IL-1, TNF, and IL-6, chemokines (e.g.,
eotaxin), neuropeptides, nitric oxide, bradykinin,
Gross: overdistended lung, with small areas of
atelectasis, occlusion of bronchi and bronchioles
by thick, tenacious mucus plugs.
Micro: the mucus plugs contain whorls of shed
epithelium, which give rise to the well-known
spiral shaped mucus plugs called Curschmann
Numerous eosinophils and Charcot-Leyden
crystals (crystalloid mad up of galactin-10)
Overall thickening of airway wall
Sub-basement membrane fibrosis (deposition of
type 1 and III collagen beneath the classic BM
composed of type IV collagen and laminin)
An increase in size of the submucosal glands
and mucous metaplasia of airway epithelial cells
Bronchial smooth muscle hyperplasia and
asthmatic attack lasts up to several
Chest tightness, dyspnea, wheezing, and
cough with or without sputum production
Cyanosis and even death.
With appropriate therapy to relieve the
attacks, most individuals with asthma are
able to maintain a productive life.
Begins in childhood, triggered by environmental
allergens , often positive family history (atopic)
Skin test causes wheel and flare reaction
Classic example of Type I IgE mediated
Initial sensitization affects T helper 2 cells, which
release IL-4/5, which promote IgE release by B
cells, mast cells and eosinophils
Reexposure to allergen-mediator release from
mucosal mast cells
Acute response: bronchoconstriction, edema,
mucus secretion, hypotension
Late phase reaction: epithelial damage and
Putative mediators: leukotrienes C4, D4, E4 and
acetylcholine; minor mediators: histamine,
Blood eosinophilia, sputum eosinophils