RESPIRATORY SYSTEM DISEASE

Object: General practitioners

Time: 04 lesson

Target:

1. Describe basic injuries of the lower respiratory tract.

2. Describe the gross and microscopic description: lobar pneumonia,

brochopneumonia, COPD.

Upper respiratory tract pathology belongs to the ENT and will not be
mentioned.

II. BASIC INJURIES

1. Tracheobronchial injuries
1.1. Hypersecretion: common, due to infections and airway irritations (cold,
allergens, toxic...).

Expression:

+ Epithelial cells are large, clear, increased secrection and weak ciliary
activity. Lamina propria is congested and edematous, submucosal mucous
glands increase secretion.

+ Secretions are removed from the body by the cough reflex. There are 2 types
of phelms:

- Thick, viscous, light yellow.

- Thin, white, foamy, may be fibrin.

1.2. Inflammatory exudate: Increased secretion, neutrophil infiltration, purulent

mucus production.
 + Purulent bronchitis: the epithelium peels off in pieces or completely, the
lamina propria becomes congested and edematous, a lot of inflammatory
exudate, fibrin, mucus, and neutrophils spill into the bronchial lumen.

+ Diphtheria: Inflammatory exudate is mainly fibrin, forming a mold that fills

the bronchial lumen, causing suffocation.

1.3. Hyperplasia and hypertrophy: occur in the epithelium, glands, cartilage,

smooth muscle, and elastic fibers. When the damage is prolonged (chronic
bronchitis), it can cause tumor.

1.4. Atrophy: Epithelium and glands, rare in muscle and cartilage, may be
interspersed with hyperplastic and hypertrophic lesions.

1.5. Metaplasia: Squamous metaplasia is in chronic inflammation; bone

metaplasia may occur from the tracheal cartilage of the elderly.

1.6. Fibrosis: Fibrosis of the bronchial spectum occurs in chronic inflammation.

1.7. Evolution:

The basic lesions can be found individually or in combination in the same

patient. They can be localized in one segment, one lobe or diffuse in both lungs.
Long-term consequences will lead to:

- Bronchial stenosis: scar fibrosis in some bronchi leads to narrowing of the

bronchial lumen, reduced ventilation and can cause difficulty breathing.

- Bronchiectasis: related to alveolar dilation; form a tubular, saccular or rosary

shape with inflammatory lesions that destroy the bronchial septa and will be
replaced by granulation tissue.

2. Alveolar injuries
2.1. Hypertrophy: Pneumocytes II are enlarged, which can further differentiate
into syncytial cells and multinucleated cells.

2.2. Atrophy and disappearance: Atrophy (other components) leads to

emphysema.

2.3. Metaplasia: Transforms into cuboidal epithelium.

2.4. Inflammatory changes: The mechanism is the hematopoietic respone in the
alveolar septum.

+ Serous alveolitis: The alveolar space is filled with edematous fluid that
stains pale pink with HE. Cells from a few alveoli sloughed off, sporadically
neutrophils, air bubbles. Damage to capillary walls causes serum to leak into
the alveoli, seen in the early stages of pneumonia.

+ Luminal hagocytic alveolitis: Pneumocytes II are are stimulated, metaplasia

and falling into the alveolar space, become macrophages. Nomally, the
number of these cells is very small. During inflammation, the number of
macrophages increases, standing in clusters clinging to alveolar walls, foamy
cytoplasm and containing phagocytic objects (bacteria, pigments, debris).

+ Hemorrhagic alveolitis: the alveoli contain degenerated red blood cells in

different stages, inflammatory exudate, and many types of inflammatory
cells. When hemorrhagic alveolitis occur on a large area, the lungs are firm
and red like the spleen, so it is called splenization. Common in bacterial
pneumonia, influenza, and circulatory stasis (heart disease, thrombosis,
pulmonary embolism, …).

+ Serofibrinous alveolitis: edema fluid in the alveoli has small fibrin fibers
forming a network that traps macrophages, red blood cells and neutrophils.
The fibrin is often close to the alveolar septum in the form of multi-layered
thin sheets, partially hyalinized.

+ Fibrinous alveolitis: The composition is thick inflammatory exudate,

forming a dense fibrin network that fills the alveoli, and may contain red
blood cells and neutrophils. When the damage spreads, the lung parenchyma
becomes as dense and solid as the liver, called hepatization. Depending on
the cellular composition in the fibrin network, divided into 2 types:

- Red hepatization: many red blood cells.

- Gray hepatization: many neutrophils.

 + Suppurative alveolitis: The alveoli contain a lot of pus (degenerated
neutrophils). Enzymes of leukocytes partially hydrolyze the fibrin network
and alveolar walls, causing loss of interalveolar septa in some places.

+ Gangrene alveolitis: Rare, caused by anaerobic bacteria, mainly due to chest

wounds by incendiary weapon. Composition: cells, debris, anaerobic
bacteria. The damage makes the lungs friable and stinky.

2.5. Progression of alveolitis

+ Inflammation regresses and disappears: Most of the above types of alveolitis

are easy to resolve, the damage can be completely recovered without leaving
a trace. Three factors determine regression and dissolution:

- Neutrophils

- Macrophages

- Antibiotic

The underlying damage has regressed and disappeared, and lung morphology and
function will return to normal.

Organizing: More common because of the constriction and antibacterial effects of

antibiotics. In prolonged illness, the inflammatory exudate and fibrin that are not
dissipated will become tissue. The fibrin fibers are hyaline, the connective tissue of
alveolar grow towards filling the alveolar lumen, with mild infiltration of chronic
inflammatory cells. Granulation tissue then forms. That injury is also called
verrucous alveolitis. The lungs become dense, firm, flesh and tough, which is
called metamorphosis.

+ Fibrosis: Rare, often accompanied by dysplasia of the covering epithelium of

the alveoli in some special cases (prolonged oxygen therapy, dust).

+ Perforation of lung parenchyma: In some cases of destructive inflammation

caused by staphylococcus Coli, fungi, amoeba, tuberculosis, etc., necrotic
lung tissue is excreted through the bronchial tract, leaving behind empty
cavities to form abscesses and cavities.
 3. Interstitial injuries
3.1. Hypertrophy

Due to excessive hyperplasia of alveolar cells, the walls become thick, narrowing
the alveolar space and can lead to atelectasis. Progresses in 3 stages:

+ Congestion and inflammatory infiltration (monocytes).

+ Fibers appear, begin to harden but recover.

+ Hardening, thick alveolar walls, irreversible, alveolar cells become cuboidal.

Lung function is seriously disturbed, leading to chronic lack of oxygen,
pneumoconiosis, and susceptibility to infectious pneumonia and fatty
pneumonia.

3.2. Atrophy

+ Alveolar walls atrophy thin, even rupture, and disappear.

+ Alveolar spaces expand.

+ Capillarial atrophy, become smaller and clogged. The consequence of

alveolar wall atrophy is alveolar dilatation, causing emphysema.

Fibrosis and smooth muscle hyperplasia

Macrophages

Osteosis dysplasia
Fibers, changing structure

4. Pleural injuries
4.1. Acute: typically produces yellowish serous fluid, fibrinous fluid, pus or
bleeding.

4.2. Chronic: Pleural fibrosis due to effusion is not resolved and become
organizing. The pleura is thick, the parietal and visceral layers is sticky. In
particular, the pleura has white speckled areas.
III. BACTERIAL PNEUMONIA

1. Lobar pneumonia (lobar topography)

1.1. Definition: Lobar pneumonia is an acute inflammatory of the lungs that
causes diffuse and uniform damage, usually in one lobe of the lung.

+ Characteristic for S. pneumoniae and K. pneumoniae

+ Seen at all ages, but more common in infants and adult >60 years old.

1.2. Pathology:

+ Gross description: Inflated lungs, obvious congestion, bruising, worsening,

and sinking when placed in water. The pleura in the damaged area has
different reactions: fibrinitis, suppurative inflammation, adhesions...

- Congestion (1-2 days): Lung tissue is swollen, heavy, red, boggy. The
section is brick, containing a lot of flesh fluid and foam, suspended in
water. It looks like a spleen, so it is also called splenization.

- Red hepatization: The damaged area is red, firm, and airless, with liver-
like consistency. The section is dry, friable, and sinks when placed in
water.

- Gray hepatization: Heavy lung tissue (1 lobe can weigh up to 1kg). The
outer surface has imprints of ribs and intercostal spaces. The lungs are
grayish brown, as dense as the liver.

+ Microscopic description:

- Congestion: diffuse serous alveolitis, vascular engorgement, intra-

alveolar fluid with few neutrophils and often bacterial colonies.

- Red hepatization: Thickened alveolar walls, edema, congestion. The

alveolar space contains massive confluent exudate with intra-alveolar
neutrophils, red cells and fibrin.

- Gray hepatization: Alveolar septa are still thick and congested, but many
areas are unclear due to dilation. The alveolar space contains progressive
 disintegration of red cells and the persistence of a fibrinosuppurative
exudate.

1.3. Evolution:

1.3.1. Recovery (over 8 days):

Neutrophils and macrophages release enzymes that gradually dissolve the

fibrin network and cells, forming viscous and then liquid fluid, which is excreted
through the bronchial tract. Neutrophils are replaced by monocytes and
macrophages. The lungs went from firm to soft, gray to pink and then back to
normal color. Phlegm changes from green and thick to yellow-red, liquid, and
scanty. Alveolar septum damage was restored intact without sequelae.

1.3.2. Complication

+ Suppuration: Rare, usually in the elderly, addicted to alcohol, drugs... The

cut area is graysih yellow, and pus flows out when pressed. If the damage
spreads, creating lung abscess, parenchymal necrosis, multi-level neutrophil
degeneration, alveolar walls are destroyed and dissolved, and surrounding
fibrous layer. In severe cases, the patient may die.

+ Organizing pneumonia:

- It is a special complication of lobar pneumonia. Lung tissue loses its

spongy, rubbery, flesh-like texture. The outer surface of the pleura is
sticky, rubbery, firm, and gray.

- On the outside of the lungs, areas of alveolar dilatation and

bronchiectasis are seen; the lungs no longer have ventilation.

+ Microscopic description: The fibrin in the alveoli is organized into fibrous

tissue. The alveolar wall remains, but fibroblasts pass through the alveolar
septum, connecting this alveolus to the adjacent alveolus. Fibrous tissue
creates scars with columnar cells (dysplastic pneumocytes) arranged around
them. The lungs lose respiratory function.

- Pleurisy

- Lung abscess
 - Mediastinitis

- Meningitis

- Otitis media and mastoiditis

- Purulent pericarditis

- Acute endocarditis

- Myocarditis

1.3.3. Comparisons:

+ Congestion: The patient has chills, high fever, chest pain, dyspnea, and fine
crackles. Phlegm is watery. This phase develops quickly within a few hours
to a day.

+ Red hepatization: in illness stage, patient has fever, dyspnea, chest pain, and
possibly cyanosis. Auscultation has murmur, dullness to percussion, and
increased vibrato. Lasts a few days to 1 week.

+ Gray hepatization: The patient has dyspnea, thick sputum, lasting a few
days. The exudate disappearing satge: fever decreases, cough, pain, phlegm
becomes thinner and less. Auscultation has coarse crackles, the patient had
less dyspnea, and his general condition was good.

2. Bronchopneumonia (lobular pneumonia)

2.1. Outline

2.1.1. Definition: Bronchopneumonia is an acute inflammatory, with some

characteristics:

+ Localized into foci, separated by relatively benign lung parenchyma.

+ There is also damage to the bronchi and lung parenchyma.

+ Damage is uneven in both space and time.

2.1.2. Cause: (many types of bacteria), common in children.

2.2. Pathology

2.2.1. Focal bronchopneumonia.

2.2.1.1. Gross descripsion:

+ Inflammatory foci scattered in the lung parenchyma, commonly found on the

back along both sides of the spine and segments 9-10 of the 2 lower lobes.

+ Both lungs are swollen and congested, the outside surface is uneven: the
benign area is slightly concave while the inflammation foci are often raised,
red or yellowish. The cross section shows the irregular injury.

- Foci with different sizes, from a few millimeters to centimeters.

- The color is patchy dark red, purple, brown, flesh, light yellow,
alternating.

+ The foci have clear boundaries, truncated cone shape, the bottom turns
towards the pleura, the top towards the hilum. When pressed, turbid liquid
flowed like pus mixed with blood, sinking into the water. The small bronchi
are congested, exuding inflammatory fluid or pus. Around the foci of
inflammation, the lung tissue is dark red, slightly firm and collapsed.

+ The pleura in the inflammation area is a bit rough. When there is an abscess,
it causes local or general empyema; Hilar lymph nodes are enlarged and
congested.

2.2.1.2. Microscopic description:

+ The diagnostic criterion is the uneven injuries: bronchitis combines different

types of alveolitis, foci are separated by normal, aerated parenchyma. The
most typical characteristic is peribronchial Charcot-Rindfleisch nodules:

+ In the center of nodule is purulent brochitis: the epithelium is ulcerated,

abruptly, the lumen is filled with fibrinous exudate, and degenerated
neutrophils. Bronchial septum edema, congestion, neutrophil infiltration.

+ Surrounding the purulent bronchitis have different forms of alveolitis: near

the bronchus, the inflammation is severe (suppurative alveolitis, fibrinous
 alveolitis), the farther away, the inflammation becomes lighter (luminal
phagocytic alveolitis, serous alveolitis), and beyond are benign alveoli.

+ Classical type has broken alveolar septums, inflammation spreads to

neighboring alveoli and far away. The farther away from injury, the milder
the inflammatory reaction becomes.

+ Atypical types, bronchitis has many forms:

- Luminal phagocytic alveolitis: hypertrophy and increased secretion of the

epithelium.

- Purulent bronchitis.

- Hemorrhagic bronchitis: full of red blood cells.

- Obstructive bronchitis: The epithelium peels off and clogs the bronchial
lumen.

+ Alveolar walls are thick, congested, hemorrhagic, and narrow alveolar

space; some places where the walls are thin.

2.2.2. Pseudolobular pneumonia:

2.2.2.1. Gross description

Dense areas of inflammation merge to large forms, occuping one lobe or the
whole lung. The damage is more severe on the back along both sides of the spine
and lower lobe. The lungs are swollen, heavy, the outer surface of the pleura is
purple. Cross sectioning observed dense, interspersed, dark inflammation foci,
slightly convex, creating a patchy color on the section surface. Squeeze the tissue
and see it is crushed, oozing fluid mixed with blood, sinking quickly under water.

2.2.2.2. Microscopic description

Charcot-Rindfleisch peribronchial nodules were not encountered. The diagnosis is

based on irregularities:

+ Bronchitis: The epithelium is damaged to varying degrees. The bronchial

lumen contains inflammatory exudate including mucus, fibrin, degenerated
 neutrophils, erythrocytes, and macrophages. Bronchial wall edema,
congestion, inflammatory cell infiltration.

+ Alveolitis: Diverse, notably suppurative alveolitis and hemorrhagic

alveolitis. Bacteria may be found in blood vessels, alveolar walls, or lumens.

2.2.3. Evolution

Depends on the bacteria causing the disease, the route of transmission, the
genetic factor, the duration, the environment... When the disease is beginning, and
the bacteria are less toxic, if treated actively, the disease will be cured. On the
contrary, the disease will progress for a long time or have complications, leaving
sequelae:

+ Lung abscess: In bronchopneumonia, some alveoli are filled with fibrin and
degenerated neutrophils called microabscesses. Because the alveoli are
destroyed, many micro-abscesses merge into one abscess with clear
boundaries, limited to a single or two segments. This complication was
common in the past but is less now. Once formed, the center is filled with
pus, surrounded by thick walls with different inflammatory reactions
depending on the stage of development.

- Adults: Large, usually one.

- Children: small size and many nests.

+ Organizing: common, cause local sclerosis in the lungs or pleura, long-term.

+ Bronchiectasis: Seen in prolonged bronchitis, with frequent coughing,

related to chronic diseases of the nasopharynx. The epithelium is destroyed
and replaced by granulation tissue. Mucous glands are enlarged,
hypersecreted and hyperplastic. There is neutrophils infiltration. Parenchyma
accompanied by alveolar ectasia or atelectasis.

2.2.4. Comparation

+ The symptoms are same but depend on the location, patient's condition, and
causative bacteria.
 + High fever, chills, tachypnea, dyspnea, tachycardia, cyanosis, and crackles in
the lungs.

3. COPD (chronic obstructive pulmonary diseases)

Chronic obstructive pulmonary disease, or COPD, refers to a group of diseases
that cause airflow blockage and breathing-related problems.

This ventilation obstruction is due to two reasons:

+ The bronchial lumen is narrowed, increasing airway resistance.

+ Parenchyma loses its ability to stretch, reducing ventilation during

exhalation.

+ COPD includes main types: chronic bronchitis and emphysema.

Ventilation obstruction is reflected by changes in respiratory function test indices

such as: increased TLC, decreased VC, decreased FEV1, FEV1/VC ratio < 0.6.

3.1. Chronic bronchitis

Expectoration more than 3 months, for at least 2 consecutive years. Prolonged

bronchitis combined with acute infections lead to fibrosis of the bronchial wall and
narrow lumen, causing symptoms of respiratory failure such as dyspnea and
cyanosis.

Characteristics:

+ Gross: Mucosa is edematous and congested. The bronchical lumen is

narrow, contains a lot of mucus and wall is thick and fibrosis.

+ Microscopic:

- Hyperplasia and hypertrophy of mucous glands in the submucosal layer.

- Increase in the number of mucus-secreting cells in the respiratory tract

(mucus-secreting cell metaplasia), decrease in the number of ciliated
cells.

- In addition, inflammatory cell infiltration and mucosal fibrosis can be

seen during acute attacks.
3.2. Emphysema

A condition of permanent dilation of the airways below the terminal

bronchioles (including respiratory bronchioles and alveoli) due to destruction of
their walls but without fibrotic reaction. Destroyed alveoli reduce the area for gas
exchange; parenchyma loses elastic fibers, reducing contraction and
hypoventilation exhalation.

Two main types:

+ Centriacinar (centrilobular) emphysema: most common, the central

respiratory bronchioles are dilated, while the alveoli in the periphery of the
lobules are normal. However, as the disease progresses, the alveoli also
become dilated, difficult to distinguish from entire lobular emphysema.
Centriacinar emphysema often occurs in the upper lobe, related to smoking,
and often has symptoms after age 50.

+ Panacinar emphysema: The entire lobule is dilated because all the

respiratory brochioles and alveoli are dilated. Panacinar emphysema occurs
in the lower lobe, is associated with α1-antitrypsin deficiency and often
shows early symptoms before age 40.

Emphysema has clinical signs when at least 1/3 of the parenchyma has been
destroyed. The patient had dyspnea, hyperpnea, barrel-shaped expansion of the
chest, gradually progressing to respiratory failure and right heart failure.

Characteristics:

+ Gross: The lungs are enlarged, covering the heart, the color is pale.

+ Microscopy: The alveoli septa is destroyed but there is no fibrous tissue

reaction, the alveoli merge to large air sacs.