Pulmonary Pathophysiology 2

8/13/2019 Pulmonary Pathophysiology 2

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Pulmonary Pathophysiology


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Reduction of Pulmonary Function

1. Inadequate blood flow to the lungs

hypoperfusion

2. Inadequate air flow to the alveoli -

hypoventilation


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Nosocomial infections

Factors that reduce airflow also compromiseparticle clearance and predispose to infection.

Restricted lung movement and ventilation mayarise due to:

Positioning

Constricting bandages

Central nervous system depression

Coma High rate of pneumonia in hospital patients due

in large part to impaired ventilation andclearance.


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Signs and Symptoms of Pulmonary

Disease

Dyspneasubjective 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. Due to:

Airway obstruction

Greater force needed to provide adequate

ventilation

Wheezing sound due to air being forcedthrough airways narrowed due to

constriction or fluid accumulation

Decreased compliance of lung tissue


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Signs of dyspnea:

Flaring nostrils

Use of accessory muscles in breathing

Retraction (pulling back) of intercostalspaces


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Cough

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:

Inflammation of lung tissue

Increased secretion in response tomucosal irritation

Inhalation of irritants

Intrinsic source of mucosal disruptionsuchas tumor invasion of bronchial wall

Excessive blood hydrostatic pressure inpulmonary capillaries

Pulmonary edemaexcess fluid passes intoairways


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When cough can raise fluid into pharynx,

the cough is described as a productive

cough, and the fluid issputum. Production of bloody sputum is called

hemoptysis

Usually involves only a small amount ofblood 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 iscalled a dry, nonproductiveor hacking

cough.

Acute cough is one that resolves in 2-3weeks from onset of illness or treatment of

underlying condition.

Us. 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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Central cyanosiscan 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 - reducedblood flow

Airway obstructionreduced ventilation

In persons with dark skin can be seenin 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 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 rubcan 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

High blood pressure in the pulmonary

circulation can cause pain during exercisethat often mistaken for cardiac pain

(angina pectoris)


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Clubbing

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

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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Two principal patterns:

1. Hypoxic Respiratory Failure:

Seen when pO2falls 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 nervousagitation, 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

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 neuromuscularabnormalities


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Pulmonary Disorders

Acute Respiratory Failure:

Acute Respiratory Distress Syndrome

(or Adult Respiratory Distress Syndrome)

Rapid and severe onset of respiratoryfailure characterized by acute lung

inflammation and diffuse injury to the

respiratory membrane with

noncardiogenic edema.


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ARDS Identified in last 25 years

Affects 200 -250 thousand people eachyear in U.S.

Mortality in persons < 60 is 40% ( 67%)

Those over 65 and immunocompromisedstill have mortality over 60 %

Most survivors have almost normal lung

function 1 year after acute illness.


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Damage can occur directly:

Aspiration of acidic gastric contents

Inhalation of toxic gases

Or indirectly:

Chemical mediators from systemicdisorders

Result is massive inflammatory response by


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Result is massive inflammatory response by

lungs

Initial injury damages the pulmonarycapillary 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

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 releasemediators that cause pulmonary

vasoconstriction pulmonary hypertension

Type II alveolar cells also damaged, seedecreased surfactant production

Alveoli fill with fluid or collapse.

Lungs become less compliant, andventilation decreases.


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After 2448 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 increasedcapillary permeability throughout the body

This leads to systemic inflammatory

response syndrome, which leads tomultiple organ dysfunction syndrome

(MODS)

Death may not be caused by ARDS alone,but by MODS

Clinical manifestations:


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Clinical manifestations: Symptoms develop progressively:

Hyperventilation repiratory alkalosisdyspnea and hypoxemia metabolic acidosis

respiratory acidosis further hypoxemia

hypotension, decreased cardiac output, death

E l ti d T t t


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Evaluation and Treatment

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

P t ti R i t F il


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Postoperative Respiratory Failure

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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Ob t ti P l Di


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Obstructive Pulmonary Disease

Characterized by airway obstruction that is

worse with expiration. More force is required toexpire a given volume of air, or emptying of

lungs is slowed, or both.

The most common obstructive diseases areasthma, chronic bronchitis, and emphysema.

Many people have both chronic bronchitis and

emphysema, and together these are oftencalled 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.

A th


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Asthma 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 allcases develop during childhood, and

another 1/3 develop before age 40

5 % of Adults and 7-10 % of children inU.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 inheritedfactors 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 inflammatoryswelling.


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Exposure to allergens or irritants causes

mast cells to release granules and trigger

the release of many inflammatorymediators 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 hyperinflationof alveoli distal to obstruction, and

increases the work of breathing


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Clinical manifestions

During remission individual isasymptomatic and pulmonary function

tests are normal

Dyspnea Often severe cough

Wheezing exhalation

Attacks usually of one to two hoursduration, 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 tohave severe bronchospasm or status

asthmaticus

If continues can be life threatening.

Management


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Management

Avoid triggers (allergens and irritants)

Patient education Acute attacks treated with corticosteroids and

inhaled beta-agonists

Chronic management based on severity ofasthma and includes regular use of inhaled

antiinflammatory medicationscorticosteroids,

chromolyn sodium or leukotriene inhibitors. Inhaled bronchodilators ***

Immunotherapyallergy shots, etc.


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Bronchoconstriction may be a normal

means of restricting airflow and intake of

irritants and allergens. Their long term usemay actually increase exposure to these

factors and cause more pronounced and

chronic symptoms. Antiinflammatory agents have better long

term effects.

COPD


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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

Associated with abnormal inflammatory

response of the lungs to noxious particlesor 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

Chronic Bronchitis


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Chronic Bronchitis 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 20times in persons who smoke and more in

persons exposed to air pollution.

P th h i l


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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 sizeand number of mucus glands and goblet cells.

Mucus is thick and tenacious, and cant be

cleared because of impaired ciliary function.

Increases susceptibility to infection and injury


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Treatment


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Treatment Best treatment is PREVENTION because

changes are not reversible. Cessation of smoking halts progression of

the disease

Bronchodilators, expectorants, and chestphysical 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

Emphysema


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Emphysema Abnormal, permanent enlargement of the

gas-exchange airways and destruction ofthe alveolar walls.

Obstruction results from changes in lung

tissue rather than mucus production andinflammation.

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 manyproteolytic enzymes which can affect lung

tissue.

With this deficiency, smokers are evenmore susceptible.


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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. Inhaled oxidants inhibit the activity of

endogenous antiproteases, and stimulate

inflammation with increased activity ofproteases.


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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 thechest, 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

Dyspnea

Barrel chest

Minimal wheezing

Prolonged expiration

Hypoventilation and polycythemia late in

the progression of the disease


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Documents

Pulmonary Pathophysiology 2