Transcript Pulmonary Pathophysiology

Pulmonary
Pathophysiology
Amal 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
Type I
 Respiratory epithelium. pneumocyte
 Connective tissue fibers,
Type I pneumocyte
Alveolar space
and cartilage: support and
maintain open air way.
 Alveolar cells (type I
and type II).
Type II
pneumocyte
Endothelium
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)
OBSTRACTIVE
RESTRICTIVE
CAUESES
Partial or complete obstruction
of the airway due to anatomic
narrowing (asthma) or loss of
elastic recoil (emphysema)
reduced expansion of the lung
parenchyma
MAJOR
DISORDERS
Asthma, emphysema, chronic
bronchitis and bronchiectasis
• chest wall disorders.
• acute (ARDS) or chronic
interstitial lung diseases
(pneumoconioses, interstitial
fibrosis and infiltrative
conditions (e.g., sarcoidosis)).
LUNG
FUNCTIONS
• Increased TLC, FVC
• Decreased expiratory flow rate
(i.e. decreased FEV1)
• the ratio of FEV1 to FVC is
decreased
• FVC is reduced
• The expiratory flow rate is
normal or reduced
proportionately.
• The ratio of FEV1 to FVC is
near normal.
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
that is irreversible.
AIRWAY REMODELING
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:
1. Modification of the risk factors.
2. Therapeutic and prophylactic anticoagulant.
3. Thrombolytic agents or surgical embolus removal in
life-threatening conditions.
2- Pulmonary HTN
Definition:
It is elevation in the mean pulmonary artery pressure 510 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.