Pulmonary Pathophysiolog

yAmal abd elmoneim

The lungs

The respiratory acinus

• Cartilage is present to level of proximal bronchioles

• Beyond terminal bronchiole gas exchange occurs

• The distal airspaces are kept open by elastic tension in alveolar walls

Histology of the lung

Respiratory epithelium.

Connective tissue fibers,

and cartilage: support and

maintain open air way.

Alveolar cells (type I

and type II).

Type I pneumocyte

Alveolar space

Type IIpneumocyte

Endothelium

Type I pneumocyte

Features of Alveoli for efficient gas exchange

• large surface area to absorb oxygen.• moist surface to allow oxygen to dissolve.• thin lining to allow easy diffusion of gases.• dense network of blood capillaries for easy gas

exchange.

Features of capillaries for efficient gas exchange:

• dense network to carry CO2 and O2

• Large surface area to transport gases• Lining is one cell thick so gases can pass through

quickly and easily.

Function of the lung

• Gas exchange

• Protection against infection by alveolar macrophages

• Surfactant secretion: allow expansion of alveoli with

air

Function of the lung

Lung function tests

• Tidal volume (TV): it is the amount of gas inhaled or exhaled

with each resting breath.

• Residual volume (RV): it is the amount of gas remaining in the

lungs at the end of maximum exhalation.

• Vital capacity (VC): it is the total amount of gas that can

exhaled following maximum inhalation.

• Total lung capacity (TLC): it is the amount of gas in the lung at

the end of maximum inhalation.

TLC = RV+ VC

Reduction of Pulmonary Function

• Inadequate blood flow to the lungs:

hypoperfusion

• Inadequate air flow to the alveoli:

hypoventilation

Classification of lung diseases into those

affecting:

(1) The airways,

(2) The interstitium, and

(3) The pulmonary vascular system.

Atelectasis

• Collapse or incomplete expansion of

part or all of the lung leading to

ventilation/perfusion imbalance and

hypoxia.

• Types:

1. Resorption (obstruction of airway).

2. Compressive (pleural effusion or

pneumothorax)

3. Contraction (fibrotic changes)

• Complications: hypoxemia, infection.

DIFFUSED LUNG DISEASES(OBSTRUCTIVE VERSUS RESTRICTIVE

PULMONARY DISEASES)

RESTRICTIVE OBSTRACTIVE

reduced expansion of the lung parenchyma

Partial or complete obstruction of the airway due to anatomic narrowing (asthma) or loss of elastic recoil (emphysema)

CAUESES

• chest wall disorders.• acute (ARDS) or chronic interstitial lung diseases (pneumoconioses, interstitial fibrosis and infiltrative conditions (e.g., sarcoidosis)).

Asthma, emphysema, chronic bronchitis and bronchiectasis

MAJOR DISORDERS

• FVC is reduced • The expiratory flow rate is normal or reduced proportionately. • The ratio of FEV1 to FVC is near normal.

• Increased TLC, FVC• Decreased expiratory flow rate (i.e. decreased FEV1)

• the ratio of FEV1 to FVC is decreased

LUNG FUNCTIONS

DIFFUSED OBSTRUCTIVE PULMONARY DISEASES

Characterized by airway obstruction that is increased

with expiration.

More force is required to expire a given volume of air.

The most common obstructive diseases are:

1- Bronchial asthma: (acute, intermittent and reversible).

2- Chronic obstructive pulmonary diseases (COPD/COLD/COAD): (irreversible)

- Emphysema. - Both

- Chronic bronchitis

Bronchial Asthma

• “Asthma is an inflammatory disorder of the

airways, which causes attacks of wheezing,

shortness of breath, chest tightness, and

coughing”.

Pathophysiology

The disease is started with:

1. Acute (immediate)-phase response (within min.): which is characterized by:

• Reversible bronchiolar constriction, • Mucus hyper-secretion • Inflammatory swelling with eosinophil

infiltration.

2. Late-phase response (after 8-24 hr.): which is characterized by sustained inflammation with bronchial hypertrophy and hyperresponsiveness.

Classification:

1. Atopic (Extrinsic) asthma:- respond to inhaled

antigen e.g. dust, pollen, animal dander, food…….

2. Non atopic (Intrinsic):- non-immune mechanisms

(cold, exercise, aspirin, stress, viral infection, air

pollutants)

Pathogenesis

1. Atopic asthma (Type I hypersensitivity i.e. allergen binds to IgE on surface of mast cells

2- Non-atopic asthma:

• The irritant induced asthma through inflammation of

the respiratory mucosa with eosinophil infiltration

• The most common irritants are viral infection,

aspirin and air pollutants.

N.B.

• Untreated, this can lead to AIRWAY REMODELING that

is irreversible.

Clinical manifestations

1. Dyspnea

2. Sometimes, cough

3. Wheezing

4. Attacks may continue from few hours to days or even weeks.

5. During remission individual is asymptomatic and pulmonary

function tests are normal

6. If bronchospam is not reversed by usual measures, the

individual is considered to have severe bronchospasm or

“status asthmaticus”

7. If continues can be life threatening.

Management

1. Avoid triggers (allergens and irritants)

2. Patient education

3. Acute attacks treated with corticosteroids and inhaled

beta-agonists

4. Chronic management based on severity of asthma and

includes regular use of inhaled antiinflammatory

medications – corticosteroids, chromolyn sodium or

leukotriene inhibitors.

5. Inhaled bronchodilators ***

6. Antiinflammatory agents have better long term effects.

COPD

• Pathological changes that cause reduced expiratory air flow

• Does not change markedly over time• Does not show major reversibility in response to

pharmacological agents• Progressive• Fourth leading cause of death in U.S.• Increasing in incidence over the past 30 years• Primary cause is cigarette smoking• Both active and passive smoking have been implicated• Other risks are occupational exposures and air

pollution• Genetic susceptibilities identified

Chronic Bronchitis

• “It is chronic productive cough with hypersecretion

of mucus for at least 3 months of the year for at least

two consecutive years”.

• Incidence may be increased up to 20 times in

persons who smoke and more in persons exposed

to air pollution.

Pathophysiology

• Inspired irritants result in inflammation of the airways with infiltration of neutrophils, macrophages, and lymphocytes into the bronchial wall.

• Causes bronchial edema and increases size and number of mucus glands and goblet cells.

• Mucus is thick and tenacious, and can’t be cleared because of impaired ciliary function.

• Increases susceptibility to infection and injury

• Initially affects only larger bronchi, but eventually all airways involved.

• Airways collapse in early expiration, blocked by mucus, and air is trapped in distal portion of the tract.

• Leads to ventilation/perfusion mismatch

• Hypoxemia occurs• Air trapping prevents

respiratory muscles from functioning efficiently (barrel chest), and get hypoventilation and hypercapnia

Treatment

• Best treatment is PREVENTION because changes

are not reversible.

• Cessation of smoking halts progression of the

disease

• Bronchodilators, expectorants, and chest physical

therapy are used as needed.

• Acute attacks may require antibiotics, steroids

• Home oxygen therapy

Emphysema

• “Abnormal, permanent enlargement of the gas-exchange

airways and destruction of the alveolar walls”.

• Obstruction results from changes in lung tissue rather than

mucus production and inflammation (pathological

changes).

• Major mechanism is loss of elastic recoil

Risk factors:

• Major cause is smoking

• Other causes are air pollution and recurrent respiratory

infections

• Primary emphysema linked to an inherited deficiency of

the enzyme alpha 1- antitrypsin which can affect lung

tissue which inhibits action of many proteolytic enzymes

which can affect lung tissue.

Normal Lung versus Emphysema

Pathophysiology

Pathophysiology

• Begins with the destruction of the alveolar septa, which

eliminates portions of the capillary bed, and increases the

volume of air in the alveolus.

• Continued alveolar loss and loss of elastic recoil

• Expiration becomes difficult, causing hyperexpansion of

the chest

• These are not effective in gas exchange and result in

hypoxia.

Types of emphysema:

1- Centriacinar (centrilobular):

Loss of elastin in the bronchioles and alveolar duct

in the upper lobules

2- Panacinar (panlobular):

The entire acini may affected esp. in the lower

lobules

Clinical manifestations

• Dyspnea at rest

• Chronic cough

• Sputum production

• Fatigue

• Anorexia and weight loss leads to malnutrition

Clinical manifestations

• Anxiety and depression

• Barrel chest

• Minimal wheezing

• Prolonged expiration

• Hypoventilation and hypoxia

Treatment

• Similar to chronic bronchitis

• Stop smoking

• Bronchodilating drugs

• Breathing retraining

• Relaxation exercises

• Antibiotics for acute infections

• Severe COPD may require inhaled or oral steroids, and

home oxygen

• Some can benefit from lung reduction surgery or lung

transplant.

(DIFFUSED RESTRICTIVE PULMONARY DISEASES)

1. Chest wall diseases:

- obesity

- impaired respiratory muscle function (poliomyelitis, mythenia gravis).

- flail chest (fructure ribs)

- kyphosis (bending of the spinal column).

2. Acute interstitial lung diseases: e.g ARDS.

3. Chronic interstitial lung diseases.

Acute Respiratory Distress Syndrome “ARDS”

• Defination:

it is a syndrome caused by diffused alveolar capillary and alveolar endothelial damage.

• Risk factors:

1. Direct : diseases affecting the lung e.g. pneumonia, trauma.

2. Indirect: systemic diseases e.g. sepsis, blood transfusion.

• It is characterized by:

1. Acute dyspnea.

2. Acute refractory hypoxaemia (not respond to O2 therapy).

3. Acute pulmonary oedema without cardiac involvement .

Pathogenesis:

1. Acute damage to capillary endothelium or alveolar epithelium and leak of fluid, inflammatory cells and RBCs into the alveolar space.

2. Neutrophils and macrophages released inflammatory mediators (IL-1, TNF and proteolytic enzymes) that cause further damage to the capillaries, type I, II pneumocytes.

3. Perfusion/ventilation mismatching (V/Q mismatch) with decreased lung surfactant and hypoxemia.

4. After 7 days respiratory fibrosis developed followed by acute respiratory failure

Chronic interstitial lung diseases( diffused interstitial lung fibrosis)

• Defination:

It is an excessive amount of fibrous or connective tissue deposition in the lung.

• Causes (risk factors):

1. Healing after chronic inflammation (scar formation).

2. After active diseases (e.g. ARDS, T.B.)

3. Inhalation of harmful substances (e.g. Coal dust, asbestos…..).

4. Idiopathic.

Pathogenesis:

• Regardless of the cause of interstitial disease the

common manifestation is (ALVEOLITIS) i.e.

accumulation of inflammatory cells esp. macrophages ,

neutrophils and lymphocytes in the alveolar wall.

• Alveolitis leading to:

Parenchymal injury (epithelium and endothelium).

activation of fibroblast proliferation.

Fibrin deposition.

• The hallmark features of theses disorders:

1. Reduced lung compliance (i.e., more pressure is required to expand the lungs because they are stiff), decreased FVC and FEV1.

2. Dyspnea and cough with or without sputum production.

3. V/Q mismatching ( due to damage of the alveolar epithelium and interstitial vasculature), hypoxemia and hypoxia.

4. Radiograph shows deposition of nodules in the lung.

5. Late stage: respiratory failure developed leading to pulmonary HTN and cor pulmonale

Examples: 1. Exposure to toxic gases (e.g. ammonia, sulpher

oxide, chlorine gases….).

2. Pneumoconiosis (i.e. inhalation of inorganic dust in the work places):

a) Silicosis: it is inhalation of free silica or silica containing compounds that cause deposition of fibrous nodules in the lung.

b) Coal worker pneumoconiosis “coal miner lung, black lung”: it is inhalation of coal dust alone or with silica.

c) Asbestosis: it is inhalation of asbestos fibers (hydrous silicate of various metals in fibrous form). The person at high risk of lung cancer.

3. Allergic alveolitis “ hypersenstivity pneumonitis”:

- it is inhalation of organic dusts (e.g. pollens, feathers, molds….).

- it is hypersenstivity reaction like bronchial asthma but differ in that; it affects the alveoli and not the bronchi.

4. Systemic diseases that cause pulmonary fibrosis or granuloma formation:

- sarcoidosis (granulomatous disease)

- collagen vascular diseases (cystic fibrosis, SLE, R.A.)

PULMONARY VASCULAR DISEASES

1. PULMONARY EMBOLISM:

DEFINATION:

• It is occlusion of portion of the pulmonary vascular bed by a thrombus (most common), a tissue fragment or an air bubble.

Risk factors

1. Venous stasis: e.g. prolonged immobilization.

2. Hypercoagulability: e.g. inherited or acquired deficiency of coagulation factors as protein S,C, oral contraceptives, malignancies.

3. Vascular endothelial injury: e.g. trauma, atherosclerosis.

4. Over obesity

5. orthopedic procedures (hip, knee)

6. No prophylaxis (DVT)

7. Abdominal/pelvic surgeries

8. Woman>30+ocp+smoker

PULMONARY EMBOLISM:

Pathophysiology:

Depending on the size of the affected pulmonary vessel and the size of the thrombus:

1. Massive occlusion: when embolus occlude the main pulm. Artery.

2. Pulmonary embolism with infarction: embolus large enough to cause infarction of portion of lung tissue.

3. Pulmonary embolism without infarction: embolus not large enough to cause infarction.

4. Multiple pulmonary emboli: chronic or recurrent

• Occlusion of part of the pulmonary circulation causes release of vasopressor agents (catecholamines, Ang.II…..) and inflammatory mediators (TXA2, Lts, free radicals…) that precipitate pulm. Vasoconstriction, pulm. HTN and cor pulmonale.

• Decreased lung surfactant leading to hypoxemia, V/Q mismatching and atelectasis.

• If the embolus is large lung infarction leading to death; if small, fibrinolytic system dissolve it.

Clinical manifestations:

1. Massive occlusion: tachypnea, dyspnea,chest pain, V/Q mismatching with hypoxemia, pulm. HTN. And cor pulmonale.

2. Emboli with infarction: dyspnea, pleural pain and pleural effusion.

3. Emboli without infarction (most common): difficult to evaluate , dyspnea, tachypnea and T.C.

4. Multiple emboli: recurrent

Diagnosis:

1. Risk factors

2. Symptoms

3. Physical examination.

4. Chest X-ray, arterial blood gases, ECG.

5. D-dimer test “ the product of thromus degradation by fibrinolytic system”

Treatment:

6. Modification of the risk factors.

7. Therapeutic and prophylactic anticoagulant.

8. Thrombolytic agents or surgical embolus removal in life-threatening conditions.

2- Pulmonary HTN

Definition:

It is elevation in the mean pulmonary artery pressure 5-10 mmHg above normal (18 mmHg).

Classification:

1. Pulm. Arterial HTN: (Primary pulm. HTN)

2. Pulm. Venous HTN (CHF)

3. Pulm. HTN caused by respiratory diseases

4. Pulm. HTN caused by thrombotic or embolic diseases.

5. Pulm. HTN caused by diseases affecting directly pulm. Vasculature.

Pathogenesis:

1- primary pulm. HTN:• Genetic dysfunction of the endothelial lining with

production of vasopressor agents leading to vascular remodeling (i.e. fibrosis and hypertrophy of the vessel wall with narrowing of the lumen), V.C., increased vascular resistance and corpulmonal.

2- secondary pulm. HTN:• COPD, pulm. Fibrosis cause chronic hypoxemia and

pulm. Artery V.C. (increased pulm. Artery pressure).• vascular remodeling leading to chronic pulmonary

HTN and corpulmonal (i.e. hypertrophy and dilation of the right ventricle)

Clinical manifestations:

Masked by signs and symptoms of right side heart failure but can be diagnosed by chest X-ray (enlarged pulmonary arteries) and ECG.

Treatment:

1- primary pulm. HTN: lung transplantation.

2- secondary pulm. HTN: treatment of the underlying cause with O2 therapy.

3- Cor pulmonale “ Pulmonary Heart Disease”

Definition:

It is right ventricular enlargement secondary to pulmonary HTN caused by lung or chest wall diseases.

Pathophysiology:

Acute hypoxemia or chronic pulm. HTN creates pressure overload on the right ventricle leading to ventricular dilation or hypertrophy (i.e. pulm. Pressure become equal the systemic pressure)

Clinical manifistations:

1. Masked by the pulm. Diseases.

2. Diagnosed by ECG (RHF), accentuated S2 sound, systemic congestion, chest X-ray and echo.

Treatment:

Treating the primary cause.