Transcript Pulmonary Pathophysiology Chap 12

Pulmonary
Pathophysiology
1
Reduction of Pulmonary
Function
1.
2.
Inadequate blood flow to the lungs –
hypoperfusion
Inadequate air flow to the alveoli hypoventilation
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Nosocomial infections
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Factors that reduce airflow also compromise particle
clearance and predispose to infection.
Restricted lung movement and ventilation may arise
due to:
– Positioning
– Constricting bandages
– Central nervous system depression
– Coma
High rate of pneumonia in hospital patients due in
large part to impaired ventilation and clearance.
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Signs and Symptoms of
Pulmonary Disease
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Dyspnea – subjective sensation of
uncomfortable breathing, feeling
“short of breath”
Ranges from mild discomfort after
exertion to extreme difficulty breathing
at rest.
Usually caused by diffuse and
extensive rather than focal pulmonary
disease.
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Dyspnea cont.
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Due to:
– Airway obstruction
 Greater force needed to provide adequate
ventilation
 Wheezing sound due to air being forced
through airways narrowed due to
constriction or fluid accumulation
– Decreased compliance of lung tissue
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Signs of dyspnea:
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Flaring nostrils
Use of accessory muscles in breathing
Retraction (pulling back) of intercostal
spaces
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Cough
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Attempt to clear the lower respiratory
passages by abrupt and forceful
expulsion of air
Most common when fluid accumulates
in lower airways
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Cough may result from:
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Inflammation of lung tissue
Increased secretion in response to
mucosal irritation
– Inhalation of irritants
– Intrinsic source of mucosal disruption – such
as tumor invasion of bronchial wall
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Excessive blood hydrostatic pressure in
pulmonary capillaries
– Pulmonary edema – excess fluid passes into
airways
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When cough can raise fluid into pharynx,
the cough is described as a productive
cough, and the fluid is sputum.
– Production of bloody sputum is called
hemoptysis
 Usually involves only a small amount of
blood loss
 Not threatening, but can indicate a serious
pulmonary disease
–Tuberculosis, lung abscess, cancer,
pulmonary infarction.
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If sputum is purulent, and infection of
lung or airway is indicated.
Cough that does not produce sputum is
called a dry, nonproductive or hacking
cough.
Acute cough is one that resolves in 2-3
weeks from onset of illness or treatment
of underlying condition.
– Usually caused by URT infections, allergic
rhinitis, acute bronchitis, pneumonia,
congestive heart failure, pulmonary embolus,
or aspiration.
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A chronic cough is one that persists for
more than 3 weeks.
In nonsmokers, almost always due to
postnasal drainage syndrome, asthma, or
gastroesophageal reflux disease
In smokers, chronic bronchitis is the most
common cause, although lung cancer
should be considered.
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Cyanosis
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When blood contains a large amount of unoxygenated
hemoglobin, it has a dark red-blue color which gives
skin a characteristic bluish appearance.
Most cases arise as a result of peripheral
vasoconstriction – result is reduced blood flow, which
allows hemoglobin to give up more of its oxygen to
tissues- peripheral cyanosis.
Best seen in nail beds
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Due to cold environment, anxiety, etc.
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Central cyanosis can be due to :
– Abnormalities of the respiratory membrane
– Mismatch between air flow and blood flow
– Expressed as a ratio of change in ventilation
(V) to perfusion (Q) : V/Q ratio
 Pulmonary thromboembolus - reduced
blood flow
 Airway obstruction – reduced ventilation
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In persons with dark skin can be seen
in the whites of the eyes and mucous
membranes.
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Lack of cyanosis does not mean
oxygenation is normal!!
– In adults not evident until severe hypoxemia
is present
– Clinically observable when reduced
hemoglobin levels reach 5 g/ dl.
– Severe anemia and carbon monoxide
poisoning give inadequate oxygenation of
tissues without cyanosis
– Individuals with polycythemia may have
cyanosis when oxygenation is adequate.
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Pain
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Originates in pleurae, airways or chest
wall
Inflammation of the parietal pleura causes
sharp or stabbing pain when pleura
stretches during inspiration
– Usually localized to an area of the chest wall,
where a pleural friction rub can be heard
– Laughing or coughing makes pain worse
– Common with pulmonary infarction due to
embolism
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Inflammation of trachea or bronchi
produce a central chest pain that is
pronounced after coughing
– Must be differentiated from cardiac pain
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High blood pressure in the pulmonary
circulation can cause pain during exercise
that often mistaken for cardiac pain
(angina pectoris)
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Clubbing
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The selective bulbous enlargement of the
end of a digit (finger or toe).
Usually painless
Commonly associated with diseases that
cause decreased oxygenation
– Lung cancer
– Cystic fibrosis
– Lung abscess
– Congenital heart disease
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Respiratory Failure
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The inability of the lungs to adequately
oxygenate the blood and to clear it of
carbon dioxide.
Can be acute:
– ARDS or pulmonary embolism
– Direct injury to the lungs, airways or chest
wall
– Indirect due to injury of another body system,
such as the brain or spinal cord.
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Chronic respiratory failure
– Due to progressive hypoventilation from airway
obstruction or restrictive disease
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Respiratory failure always presents a serious
threat
– Dysnpea always present, but may be difficult to
detect a change in a chronic patient
– Since nervous tissue it highly oxygen-dependent,
see CNS signs and symptoms
– Memory loss, visual impairment, drowsiness
– Headache due to increased intracranial pressure
due to cerebral vasodilation
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Two principal patterns:
1.
Hypoxic Respiratory Failure:
Seen when pO2 falls to or below 60 mm Hg
Typically seen in chronic bronchititis and
emphysema, in lung consolidation due
to bacterial infection, or in lung
collapse, pulmonary hypertension,
pulmonary embolism and ARDS.
Initially, produces headache and nervous
agitation, soon followed by a decline in
mental activity, and confusion.
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With a progressive lowering of pO2, more
widespread tissue damage and loss of
consciousness can be expected.
In the event of brain stem hypoxia, CNS
output to the heart and systemic arterioles
can produce circulatory shock
Renal hypoxia can cause loss of
homeostatic balance and accumulation of
wastes to complicate the problem
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Hypoxic-Hypercapnic
Respiratory Failure
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When arterial pCO2 (normally 40 mm
Hg) exceeds 45 mm HG, condition is
called hypercapnia
Most often, obstructive conditions
produce this form of respiratory
failure, as can hypoventilation from
CNS problem, thoracic cage or
neuromuscular abnormalities
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Attempts to compensate include increased
heart rate and vasodilation, which
produces warm, moist skin.
CNS effects produce muscular tremors,
drowsiness and coma.
Hypercapnia also produces acidosis.
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Pulmonary Disorders
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Acute Respiratory Failure:
– Acute Respiratory Distress Syndrome
(or Adult Respiratory Distress Syndrome)
 Rapid and severe onset of respiratory
failure characterized by acute lung
inflammation and diffuse injury to the
respiratory membrane with
noncardiogenic edema.
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ARDS
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Identified in last 25 years
Affects 200 -250 thousand people each
year in U.S.
Mortality in persons < 60 is 40% (↓ 67%)
Those over 65 and immunocompromised
still have mortality over 60 %
Most survivors have almost normal lung
function 1 year after acute illness.
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Pathophysiology of ARDS
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All disorders causing ARDS acutely injure
the respiratory membrane and produce
severe pulmonary edema, shunting, and
hypoxemia.
– Shunting: blood flow is normal, but gas
exchanged is decreased. V/Q ratio changes:
the same effect as if blood were shunting or
bypassing the lungs.
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Damage can occur directly:
– Aspiration of acidic gastric contents
– Inhalation of toxic gases
Or indirectly:
– Chemical mediators from systemic
disorders
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Result is massive inflammatory
response by lungs
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Initial injury damages the pulmonary capillary
epithelium, causing platelet aggregation and
intravascular thrombus formation.
Platelets release substances that attract and
activate neutrophils.
Damage also activates the complement cascade
which also activates neutrophils and the
inflammatory response.
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Role of neutrophils is central to the
development of ARDS.
Neutrophils release inflammatory mediators:
– Proteolytic enzymes
– Toxic oxygen products
– Prostaglandins and leukotrienes
– Platelet activating factors
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These damage the respiratory membrane and
increase capillary permeability, allowing fluids,
proteins, and blood cells to leak into alveoli →
pulmonary edema and hemorrhage
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Reduces pulmonary ventilation and
compliance
Neutrophils and macrophages release
mediators that cause pulmonary
vasoconstriction → pulmonary hypertension
Type II alveolar cells also damaged, see
decreased surfactant production
Alveoli fill with fluid or collapse.
Lungs become less compliant, and
ventilation decreases.
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After 24 – 48 hours hyaline
membranes form
After about 7 days, fibrosis
progressively obliterates the alveoli,
respiratory bronchioles and
interstitium
Result is acute respiratory failure
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In addition, chemical mediators often
cause widespread inflammation,
endothelial damage and increased
capillary permeability throughout the body
This leads to systemic inflammatory
response syndrome, which leads to
multiple organ dysfunction syndrome
(MODS)
Death may not be caused by ARDS alone,
but by MODS
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Clinical manifestations:
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Symptoms develop progressively:
– Hyperventilation→ repiratory alkalosis→
dyspnea and hypoxemia→ metabolic acidosis→
respiratory acidosis → further hypoxemia →
hypotension, decreased cardiac output, death
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Evaluation and Treatment
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Diagnosis based on physical examination,
blood gases and imaging
Treatment is based on early detection,
supportive therapy and prevention of
complications, esp. infection
Often requires mechanical ventilation
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Many studies underway for treatment:
– Prophylactic immunotherapy
– Antibodies against endotoxins
– Inhibition of inflammatory mediators
– Inhalation of nitric oxide to reduce pulmonary
hypertension
– Surfactant replacement
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Postoperative Respiratory Failure
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Same pathophysiology as ARDS, but usually not as
severe.
Smokers are at risk, esp. if have pre-existing lung
disease.
Also individuals with chronic renal failure, chronic
hepatic disease, or infection
Thoracic and abdominal surgeries carry greatest risk
Individuals usually have a period of hypotension
during surgery, and many have sepsis.
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Prevention includes:
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Frequent turning
Deep breathing (spirometry)
Early ambulation to prevent atelectasis
and accumulation of secretions
Humidification of air to loosen secretions
Supplemental oxygen and antibiotics as
appropriate
Respiratory failure may require mechanical
ventilation for a time.
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Obstructive Pulmonary Disease
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Characterized by airway obstruction that is worse with
expiration. More force is required to expire a given
volume of air, or emptying of lungs is slowed, or both.
The most common obstructive diseases are asthma,
chronic bronchitis, and emphysema.
Many people have both chronic bronchitis and
emphysema, and together these are often called
chronic obstructive pulmonary disease - COPD
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Major symptom of obstructive pulmonary
disease is dyspnea, and the unifying sign
is wheezing.
Individuals have increased work of
breathing, V/Q mismatching, and a
decreased forced expiratory volume.
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Asthma
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More intermittent and acute than COPD,
even though it can be chronic
Factor that sets it apart from COPD is its
reversibility
Occurs at all ages, approx. half of all cases
develop during childhood, and another 1/3
develop before age 40
5 % of Adults and 7-10 % of children in
U.S. have asthma
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Morbidity and mortality have risen in past 20 years in
spite of increased numbers and availability of
antiasthma medications.
Runs in families, so evidence genetics plays a role.
Environmental factors interact with inherited factors
to increase the risk of asthma and attacks of
bronchospasm
Childhood exposure to high levels of allergens,
cigarette smoke and/or respiratory viruses increases
chances of developing asthma.
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The major pathological feature of asthma
is inflammation resulting in
hyperresponsiveness of the airways.
Major events in an acute asthma attack
are bronchiolar constriction, mucus
hypersecretion, and inflammatory
swelling.
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Exposure to allergens or irritants causes
mast cells to release granules and trigger
the release of many inflammatory
mediators such as histamine, interleukins,
immunoglobulins, prostaglandins,
leukotrines and nitric oxide.
See vasodilation and increased capillary
permeability
Chemotactic factors attract neutrophils,
eosinophils and lymphocytes to the area –
bronchial infiltration
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Smooth muscle spasm in bronchioles due
to IgE effect on autonomic neurons - ACh
Vascular congestion
Edema formation
Production of thick, tenacious mucus
Impaired mucociliary function
Thickening of airway walls
Increased bronchial responsiveness
Untreated, this can lead to airway
damage that is irrevesible.
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Obstruction increases resistance to air
flow and decreases flow rates
Impaired expiration causes hyperinflation
of alveoli distal to obstruction, and
increases the work of breathing
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Clinical manifestions
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During remission individual is
asymptomatic and pulmonary function
tests are normal
Dyspnea
Often severe cough
Wheezing exhalation
Attacks usually of one to two hours
duration, but may be severe and continue
for days or even weeks.
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If bronchospam is not reversed by usual
measures, the individual is considered to
have severe bronchospasm or status
asthmaticus
If continues can be life threatening.
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Management
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Avoid triggers (allergens and irritants)
Patient education
Acute attacks treated with corticosteroids and inhaled
beta-agonists
Chronic management based on severity of asthma
and includes regular use of inhaled antiinflammatory
medications – corticosteroids, chromolyn sodium or
leukotriene inhibitors.
Inhaled bronchodilators ***
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Immunotherapy – allergy shots, etc.
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Bronchoconstriction may be a normal
means of restricting airflow and intake of
irritants and allergens. Their long term use
may actually increase exposure to these
factors and cause more pronounced and
chronic symptoms.
Antiinflammatory agents have better long
term effects.
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COPD
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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
Associated with abnormal inflammatory
response of the lungs to noxious particles
or gases.
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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
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Chronic Bronchitis
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Hypersecretion of mucus and chronic
productive cough for at least 3 months
(usually winter) 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.
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Pathophysiology
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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
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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.
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Treatment
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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
and possibly mechanical ventilation.
Chronic oral steroids as a last resort.
Home oxygen therapy
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Emphysema
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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.
Major mechanism is loss of elastic recoil
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Major cause is cigarette smoking
Other causes are air pollution and
childhood respiratory infections
Primary emphysema linked to an
inherited deficiency of the enzyme alpha
1- antitrypsin which inhibits action of
many proteolytic enzymes which can
affect lung tissue.
With this deficiency, smokers are even
more susceptible.
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Pathophysiology
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Begins with the destruction of the alveolar
septa, which eliminates portions of the
capillary bed, and increases the volume of
air in the alveolus.
Inhaled oxidants inhibit the activity of
endogenous antiproteases, and stimulate
inflammation with increased activity of
proteases.
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See continued alveolar loss and loss of
elastic recoil
Expiration becomes difficult
Hyperinflation of alveoli produce large air
spaces (bullae) and air spaces adjacent to
the pleura (Blebs)
These are not effective in gas exchange
and result in hypoxemia
Air trapping causes hyperexpansion of the
chest, which puts respiratory muscles at a
mechanical disadvantage.
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This makes breathing so difficult that
late in the disease individuals develop
hypoventilation and hypercapnia.
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Clinical manifestations
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Dyspnea
Barrel chest
Minimal wheezing
Prolonged expiration
Hypoventilation and polycythemia late
in the progression of the disease
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Treatment
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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.
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