Pathophysiology of The respiratory system

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Pathophysiology of The respiratory system
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Objectives

• Classifying different respiratory diseases.
• Defining the different predisposing factors for
  respiratory diseases.
• Studying different manifestations of the most
  important respiratory diseases.
• Studying the social effects of the most common
  respiratory diseases.
• Studying the main steps of prevention and control
  of the respiratory diseases.

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These respiratory diseases include

• Infections such as pneumonia.
• Obstructive disorders that obstruct airflow into
  and out of the lungs such as asthma, bronchitis
  and emphysema.
• Restrictive disorders are conditions that limit
  normal expansion of the lungs such as
  pneumothorax, atelectasis, respiratory distress
  syndrome and cystic fibrosis.

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These respiratory diseases include(cont.)

• Neoplasms abnormal growth of tissues that can
  be benign or malignant.
• Inhalation of particles such as noxious gases
  and pollens that can alter the pulmonary
  function.
• Vascular diseases such as epistaxis, pulmonary
  oedema and pulmonary embolism.

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HEALTHY HABITS FOR CARING FOR OUR RESPIRATORY
SYSTEM

• Exercise regularly, this helps to improve the
  circulation of the blood.
• Eat a well balanced diet.
• Eat vegetables, especially green vegetables, and
  fruits.
• Avoid eating too much saturated fats. Use
  beneficial fats and oils.
• Maintain a healthy weight.
• Live in a clean environment.

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HEALTHY HABITS FOR CARING FOR OUR RESPIRATORY
SYSTEM (cont.)

• Avoid smoking cigarettes and second hand smoke.
  Smoking increases the risk of stroke and coronary
  heart disease.
• Have a positive outlook in life.
• Try to reduce stress and tension.
• Avoid high blood pressure because this can cause
  heart failure and stroke.

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Respiratory System DiseasesGeneral Outline

• Infectious diseases
• Upper
• URI
• Croup
• Epiglottitis
• Flu (Influenza)
• Lower
• Bronchiolitis (RSV)
• Pneumonia
• SARS
• TB
• Fungal diseases
• Obstructive lung diseases
• Cystic fibrosis
• Cancer
• Aspiration pneumonia
• Asthma

• COPD (chronic obstr. pulm. dis)
• Emphysema
• Chronic bronchitis
• Restrictive lung diseases
• Chest wall abnormalities
• Connective tissue abnormalities
• Pneumoconioses
• Vascular disorders
• Pulmonary edema
• Pulmonary embolism
• Expansion disorders
• Atelectasis
• Pleural effusion
• Pneumothorax
• Resp. distress syndrome
• Infant adult types.

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Infectious diseases

• Upper respiratory tract
• URI
• Croup
• Epiglottitis
• Flu (Influenza)
• Lower respiratory tract
• Bronchiolitis (RSV)
• Pneumonia
• SARS
• TB
• Fungal diseases

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The Upper Respiratory System

• Consists of
• Nose
• Pharynx (throat)
• Middle ear
• Eustachian tubes

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Upper Respiratory System defense Mechanisms

• Coarse hairs in the nose filter large particles
  from air entering the respiratory tract.
• The ciliated mucous membranes of the nose and
  throat trap airborne particles and remove them
  from the body.
• Lymphoid tissue, tonsils, and adenoids provide
  immunity to certain infections.

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Microbial Diseases of the Respiratory System

• Infections of the upper respiratory system are
  the most common type of infection.
• Pathogens that enter the respiratory system can
  infect other parts of the body.

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• Most respiratory tract infections are
  self-limiting.
• Often caused by bacteria viruses in combination.

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• Upper respiratory system

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The Lower Respiratory System

• Consists of
• Larynx
• Trachea
• Bronchial tubes
• Alveoli
• Pleura

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Structures of Lower Respiratory System
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The Lower Respiratory System Defense Mechanisms

• The ciliary escalator of the lower respiratory
  system helps prevent microorganisms from reaching
  the lungs.
• The normal microbiota (nasal flora) of the nasal
  cavity and throat can include pathogenic
  microorganisms.
• Microbes in the lungs can be phagocytozed by
  alveolar macrophages.
• Respiratory mucus contains IgA antibodies.

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Mucocilary Escalator

• The lower respiratory system is usually sterile
  because of the action of the ciliary escalator.
• Microorganisms hoping to infect the respiratory
  tract are caught in the sticky mucus and moved up
  by the mucociliary escalator.

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• General Manifestation of respiratory disease
• Sneezing reflex response to irritation of upper
  respiratory tract
• Coughing reflex response to irritation of lower
  respiratory tract
• Sputum production
• If yellowish- green ------ infection
• If rusty ------- blood pus pneumococcal
  pneumonia
• If bloody (hemoptysis) usually frothy , seen in
  pulm. Edema
• Also seen in pulm. TB cancer
• Large amounts foul bronchiectasis
  (suppuration).
• Thick sticky asthma, cystic fibrosis

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General Manifestation of respiratory disease
(cont.)

• Hypoxemia Decreased levels of oxygen in
  arterial blood
• Hypercapnia Increased levels of CO2 in the
  blood
• Hypocapnia Decreased levels of CO2 in the blood
• Hypoxia Decreased levels of oxygen in the
  tissues
• Dyspnea Difficulty breathing (shortness of
  breath).
• Tachypnea Rapid rate of breathing

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General Manifestation of respiratory disease
(cont.)

• Breathing patterns eupnia, labored (dyspnea) ,
  wheezing, stridor
• Breath sounds normal, rales ( rhonchi,
  crepitations) decreased breath sounds.
• Cyanosis Bluish discoloration of skin and
  mucous membranes due to poor oxygenation of the
  blood.
• Hemoptysis Blood in the sputum

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Patterns of Breathing

• Apnea temporary cessation of breathing (one or
  more skipped breaths)
• Dyspnea labored, gasping breathing shortness
  of breath
• Eupnea normal, relaxed, quiet breathing
• Hyperpnea increased rate and depth of breathing
  in response to exercise, pain, or other
  conditions
• Hyperventilation increased pulmonary
  ventilation in excess of metabolic demand
• Hypoventilation reduced pulmonary ventilation
• Orthopnea Dyspnea that occurs when a person is
  lying down
• Respiratory arrest permanent cessation of
  breathing
• Tachypnea accelerated respiration

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Respiratory infections

• Infections of the respiratory tract can occur in
• The upper respiratory tract.
• The lower respiratory tract.
• Both.
• Organisms capable of infecting respiratory
  structures include
• bacteria.
• viruses the majority of upper respiratory tract
  infections are caused by viruses as rhinovirus
  and parainfluenza virus.
• fungi.

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Upper respiratory tract Infections
Pharyngitis inflammation of the
pharynx Laryngitis swelling and irritation
(inflammation) of the voice box
(larynx) Tonsillitis inflammation of the
tonsils Sinusitis inflammation of the sinuses
Epiglottitis inflammation of the cartilage that
covers the trachea H. influenzae type b
most threatening
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Acute Chronic Pharyngitis

• Inflammation of the pharynx.
• Most common throat disorder.
• Acute (viral,streptococcal bacteria, etc).
• Chronic (allergy, persistent cough, etc).
• Treatment Varies with etiology.

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Acute Chronic Laryngitis

• Inflammation of the larynx vocal cords.
• Acute viral or bacterial infections, excessive
  use of the voice, inhalational injuries (dust or
  chemicals).
• Chronic often due to other ENT diseases
  (polyps, sinusitis, allergies, etc).
• Treatment
• Varies with etiology.

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Sinusitis

• Inflammation of the paranasal sinuses.
• Acute (infection viral or bacterial).
• Chronic (often allergic or hyperplastic).
• Treatment
• Varies with type.

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Upper respiratory tract Infections

• Viral Infections

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The Common Cold

• Cause rhinovirus, parainfluenza virus,
  respiratory syncytial virus, adenovirus and
  coronavirus.
• The disease has seasonal variations in peak
  incidence.
• Mode of infection through the nasal mucosa and
  the surfaces of the eye via respiratory
  secretions.
• Manifestations
• Rhinitis Inflammation of the nasal mucosa
  (discharge).
• Sinusitis Inflammation of the sinus mucosa
  (headache).
• Pharyngitis Inflammation of the pharynx (sore
  throat).

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• Any one of approximately 200 different viruses
  can cause the common cold Rhinoviruses cause
  about 50 of all colds.
• Coronaviruses (1520)
• Symptoms include sneezing, nasal secretions, and
  congestion.

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Influenza

• Influenza is a viral infection that can affect
  the upper or lower respiratory tract. It is a
  highly transmissible respiratory pathogen.
• Because the viral has a high tendency for genetic
  mutation, new variant of the virus are constantly
  arising allover the world. Serious pandemics
  (spread of infection across a large region) of
  influenza are seen every 8 to 10 years as a
  result of this genetic mutation .

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What is influenza?

• RNA virus that has three classes
• Influenza A, the most common.
• Disease in humans, can cause pandemics
• Influenza B
• Inflects humans, less severe than type A
• Influenza C
• Infects pigs and humans, generally mild disease

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Structure of the flu virus

• RNA virus
• Outer lipid coat
• Projections on the outer layer
• Hemagglutin spikes (H) 16 types
• Neuraminidase spikes (N) 9 types

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Influenza virus
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Spikes

• Hemagglutinin spikes
• 500 per virus
• Allows virus to recognize and attach to body
  cells
• Antibodies made to these spikes

• Neuraminidase spikes
• 100 per virus
• Help virus separate from infected host cell

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• Symptoms of influenza infection
• Headache, Fever, chills, Muscle aches, Nasal
  discharge, Unproductive cough, Sore throat.
• Influenza infection can cause acute tissue damage
  and a loss of ciliated cells that protect the
  respiratory passages from other organisms.
• Can cause co-infection of the respiratory
  passages with bacteria.
• The virus can infect the tissues of the lung
  itself to cause a viral pneumonia.

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• Treatment of influenza mainly symptomatic.
• Bed rest, fluids, warmth, Antiviral drugs.
• Influenza vaccine
• Protects against certain A and B influenza
  strains that are expected to be prevalent in a
  certain year.
• The vaccine must be updated and administered
  yearly to be effective but will not be effective
  against influenza strains not included in the
  vaccine.
• The influenza vaccine is particularly indicated
  in elderly people, in individuals weakened by
  other disease and in health-care workers

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• Drugs for Treating Influenza
• Amantidine.
• Used orally or by aerosol administration
• Effective only against type A influenza
• Inhibits viral fusion, assembly and release from
  the infected host cell
• Neuraminidase inhibitors (Zanamavir,
  Oseltamivir).
• New drugs that can be used by inhalation
  (Zanamavir) or orally (Oseltamivir)
• Effective against both type A and B influenza
• Inhibits the activity of viral neuraminidase
  enzyme that is necessary for spread of the
  influenza virus

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Influenza Serotypes and epidemic incidence
Type Antigenic Subtype Year Severity
A H3N2 H1N1 H2N2 H3N2 H1N1 1889 1918 1957 1968 1977 Moderate Severe pandemic Severe Moderate Low
B None 1940 Moderate
C None 1947 Very mild
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Why do I need to get a new flu shot every year?

• Antigenic drift changes in the structure of the
  spikes that allow the virus to evade the immune
  system. It occurs on an annual basis
• Antigenic shift major change in the protein of
  the spikes that creates a virus that is new to
  the human population little herd immunity major
  epidemics.

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Croup

• Inflammation of the upper airways (the subglottic
  area)
• Viral etiology
• Winter illness
• Usually in infants up to 3 YOA
• S/S barking (seal-like) cough, worse when supine
• Treatment humidified air, cool air

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Infectious Mononucleosis

• Acute viral infection
• Usually adolescents young adults
• Sore throat, fever, enlarged cervical LN
• Etiology Epstein-Barr virus (EBV)
• Disease episodes of the above symptoms,
  fatigue, splenomegaly, often 6-8 week course.
• Treatment pain fever relief, steroids in some
  cases.

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Upper respiratory tract Infections

• Bacterial Infections

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Streptococcal throat inection
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Streptococcal pharyngitis

• Streptococcus pyogenes
• Beta hemolysis on blood agar from throat swab
• Sore throat, fever, swelling of tonsils and neck
• Sensitive to Penicillin

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• Also called strep throat
• Streptococcus pyogenes
• Gram positive cocci chains
• Resistant to phagocytosis
• Streptokinases lyse clots
• Streptolysins are cytotoxic
• Diagnosis by enzyme immunoassay (EIA) tests (have
  replaced latex agglutination tests)

Characterized by lack of cough
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Scarlet Fever

• Streptococcus pyogenes
• Pharyngitis
• Erythrogenic toxin produced by lysogenized S.
  pyogenes
• Symptoms include a red rash (sandpaper), high
  fever, and a red, enlarged tongue.

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Acute Tonsillitis

• Tonsillar inflammation
• Acute or chronic
• Most common infection
• Strep pyogenes, Staphylococcus aureus
• S/S sore throat, hoarseness, fever, dysphagia
• Treatment antibiotics

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Otitis Media

• Middle ear infection
• Common in young children
• Bacteria enter the middle ear from the oropharynx
  via the short internal auditory tube
• Painful swelling of ear drum

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• Various bacteria cause the condition, mainly
  Streptococcus and Staphylococcus.
• Children generally outgrow the condition.
• Amoxicillin is used but this treatment is
  currently being phased out to limit resistance.

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Diphtheria

• Corynebacterium diphtheriae Gram-positive rods
• Diphtheria toxin produced by lysogenized C.
  diphtheriae.

• A membrane, containing fibrin and dead human and
  bacterial cells, forms in the throat and can
  block the passage of air.

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Diphtheria membrane

• Fibrin, tissue, bacterial cells

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• Still common in developing countries where
  immunizations aren't given routinely.
• Up to 40 to 50 of those who don't get treated
  can die.
• The exotoxin inhibits protein synthesis, and
  heart, kidney, or nerve damage may result.
• Prevented by DTaP vaccine.
• Diphtheria toxoid.

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• Symptoms includes fever, sore throat, malaise,
  swelling of the neck and tough grayish membrane
  forms in the throat from the infection
• Cutaneous diphtheria (esp. in persons gt30 yrs).
  It is infected skin wound leads to slow-healing
  ulcer.
• Treated by erythromycin or penicillin

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Lower Respiratory Tract Infection
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Lower respiratory tract Infections

• The respiratory tract is protected by a number of
  very effective defense mechanisms designed to
  keep infectious organisms and particulates from
  reaching the lungs .
• For an organism to reach the lower respiratory
  tract, the organism must be particularly virulent
  and present in very large number or the host
  defense barriers must be weakened.

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• Lower respiratory system
• Contains the larynx, trachea, bronchial tubes,
  and lungs

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• Factor that might weaken the respiratory defense
  barriers
• Cigarette smoking, which can paralyze the cilia
  lining the cells of the respiratory passages and
  impair removal of secretions, particles and
  microorganisms.
• The presence of a respiratory pathogen such as
  the cold or influenza virus .

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• Defenses of the Respiratory System
• Moist, mucus-covered surfaces Trap particles
  and organisms
• Cell surface IgA, lysosomes
• Ciliated epithelium Clears trapped particles
  and organisms from airway passages
• Cough reflex and epiglottis Prevents aspiration
  of particles and irritants into lower airways
• Pulmonary macrophages Phagocytize foreign
  particles and organisms in the alveolar spaces

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Lower Respirator Tract Infection

• Bacteria, viruses, and fungi cause
• Bronchitis
• Bronchiolitis
• Pneumonia

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Lower respiratory tract Infections

• Bacterial Infections

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• Pneumonia
• Pneumonia is a condition that involves
  inflammation of lower lung structures such as the
  alveoli or interstitial spaces.
• It may be caused by bacteria such as Pneumococci
• The prevalence and severity of pneumonia have
  been heightened in recent years due to the
  emergence of HIV as well as antibiotic
  resistance.
• There tend to be distinct organisms that cause
  pneumonia in the hospital setting vs. the
  community setting.

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Predisposing Factors

• Individuals Most at Risk for Pneumonia
• Elderly
• Those with viral infection
• Chronically ill
• AIDS or immunosuppressed patients
• Smokers
• Patients with chronic respiratory disease e.g.
  bronchial asthma.

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Types of pneumonia

• Community acquired pneumonia (CAP)
• Aspiration pneumonia
• Hospital
• Hospital acquired pneumonia (HAP)
• Ventilator associated pneumonia (VAP)
• Healthcare associated pneumonia (HCAP)

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Potential Pathogens

• Typical
• Streptococcus pneumoniae (Pneumococci).
• Hemophilus influenzae
• Mycobacterium catarrhalis
• Klebsiella pneumoniae
• Atypical
• Chlamydia pneumoniae
• Legionella pneumophila
• Mycoplasma pneumoniae.

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Other Potential Pathogens

• Viruses
• Fungi
• Less Common pathogens
• N. meningitidis
• Chlamydia psittaci
• B. anthracis
• Y. pestis

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Other classification of pneumonia

• A second classification scheme for pneumonia is
  based on the specific structures of the lung that
  the organisms infect and includes typical and
  atypical pneumonia.
• 1-Typical pneumonia
• Usually bacterial in origin.
• Organisms replicate in the spaces of the
  alveoli.
• Manifestations
• Inflammation and fluid accumulation are seen in
  the alveoli.
• White cell infiltration and exudation can been
  seen on chest radiographs.
• High fever, chest pain, chills, and malaise are
  present.
• Purulent sputum is present.
• Some degree of hypoxemia is present.

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• 2- Atypical pneumonia
• Usually viral in origin.
• Organisms replicate in the spaces around the
  alveoli.
• Manifestations
• Milder symptoms than typical pneumonia.
• Lack of white cell infiltration in alveoli.
• Lack of fluid accumulation in the alveoli.
• Not usually evident on radiographs.
• May make the patient susceptible to bacterial
  pneumonia.

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• 3- Opportunistic organisms
• A number of organisms can cause severe
  respiratory infections and pneumonia in patients
  with immunocompromisation (eg. HIV virus or as a
  result of immune suppressive therapy).
• These organisms include mycobacteria, fungus
  (Histoplasma) and fungi (Pneumocystis carinii).
  They rarely affect healthy people.
• Treatment of these organisms requires specific
  drug therapy.

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• Treatment of pneumonia
• Antibiotics if bacterial in origin. The
  health-care provider should consider the
  possibility that antibiotic-resistant organisms
  are present. Other causative agent are treated
  accordingly(eg . Antiviral, antifungal and anti
  protozoal).
• Oxygen therapy for hypoxemia.
• A vaccine for pneumococcal pneumonia is
  currently available and highly effective. This
  vaccine should be considered in high-risk
  individuals.

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Pertussis (Whooping Cough)

• Bordetella pertussis
• Gram-negative coccobacillus.
• Encapsulated.
• Aerosal Transmission from human to human.

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• Pathogenesis
• Tracheal cytotoxin of cell wall damaged ciliated
  cells
• Pertussis toxin
• Prevented by DTaP vaccine (acellular Pertussis
  cell fragments)

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• Clinical picture of Pertussis.
• Stage 1 Catarrhal stage, like common cold.
• Stage 2 Paroxysmal stageviolent coughing
  sieges.
• Stage 3 Convalescence stage.

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Mycoplasma pneumonia

• Atypical pneumonia caused by the bacteria
  Mycoplasma pneumoniae
• Bacteria has no cell wall
• More common in young adults (under 40) and
  children
• Symptoms are low grade fever, cough, headache
  that may last for several weeks
• Treated with erythromycin and tetracycline

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Tuberculosis

• Lung infection caused by the acid-fast bacteria
  Mycobacterium tuberculosis.
• Acquired by inhalation
• Strong immune system often will prevent the
  bacteria from causing infection
• Weak immune system or poor general health can
  lead to infection and possibly death

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Mycobacterium tuberculosis
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Types of Mycobacteria

• M. bovis lt1 U.S. cases not transmitted from
  human to human usually affect the bones or
  lymphatic system.
• M. avium-intracellulare complex infects people
  with late-stage HIV infection.
• - The mycolic acids of the cell wall are an
  important factor in the pathogenicity.

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• - Mycolic acids also gives it resistance to
  drying and disinfectants.
• - Lesions formed by M. tuberculosis are called
  tubercles dead macrophages and bacteria form the
  caseous lesion that might calcify and appear in
  an X-ray image as a Ghons complex.

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Ghons complex
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Pathogenesis of TB

• Bacteria are ingested by lung macrophages but are
  not killed.
• Bacteria multiply inside the macrophages.
• Infected macrophages are isolated in the lungs in
  lesions called tubercles.
• The tubercles can rupture and release bacteria
  into the body to cause systemic disease and
  infection to others.
• Symptoms include weight loss, coughing blood,
  loss of vigor, wasting and death.

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The Pathogenesis of Tuberculosis
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The Pathogenesis of Tuberculosis
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The Pathogenesis of Tuberculosis
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The Pathogenesis of Tuberculosis
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The Pathogenesis of Tuberculosis
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Diagnosis of Tuberculosis

• Tuberculin skin test screening
• Positive reaction means current or previous
  infection
• Followed by X-ray or CT exam, acid-fast staining
  of sputum, culturing of bacteria and PCR TEST for
  TB.

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TB Testing

• Tuberculin skin test is used to screen for the
  disease
• Test results
• if you have had TB
• if you have been exposed but never had active
  TB
• if you have been vaccinated
• - never had or been exposed to the disease

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A Positive Tuberculin Skin Test

• A positive tuberculin skin test can indicate
  either an active case of TB, prior infection, or
  vaccination and immunity to the disease.

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Incidence of TB

• 20,000 new cases in the US each year
• Incidence decreasing in the US
• Estimated 1/3 of the world population is infected
• 10-12 million deaths per year from TB
• Antibiotic resistant strains are emerging

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Treatment

• Long term antibiotic therapy with antibiotic such
  as isoniazid, rifampin, and pyrazinamide
• Vaccination with the BCG vaccine
• Vaccine effectiveness is questionable used in
  much of the world except the US

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Pleurisy/ Pleuritis

• Inflamation of parietal visceral pleura.
• May be primary or secondary.
• Etiology
• Infection, SLE, traumatic, etc.
• S/S Pleuritic or sharp chest pain.
• Treatment pain relief and treatment of
  underlying cause.

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Lung Abscess

• Area of necrotic purulent lung
• More common in dependent areas of lungs and in
  right lung
• May be caused by pneumonias or by spread of
  infection by blood from other areas of the body
• Testing treatment Often seen on CXR,
  antibiotics possible excision

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Legionnaires Disease(Legionella Pneumonia)

• Pneumonia caused by bacteria
• Legionella pneumophilia.
• Named for 1976 outbreak at an American Legion
  convention
• Severity varies
• S/S nonproductive cough at first, then grayish
  sputum
• Treatment antibiotics

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Lower respiratory tract Infections

• Fungal Infections

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Fungal Infections

• Fungal spores are easily inhaled they may
  germinate in the lower respiratory tract.
• The incidence of fungal diseases has been
  increased in recent years.
• The mycoses can be treated with amphotericin B.

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Coccidiodomycosis

• Fungal disease of the lungs
• Coccidiodes immitis
• Endemic to the desert southwest
• Causes either no symptoms or mild symptoms,
  including chest pain, fever, coughing, and weight
  loss
• Immune suppressed individuals may develop a TB
  like disease that can become systemic
• Amphotericin B is used to treat the condition

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Histoplasmosis

• Histoplasma capsulatum, dimorphic fungus
• Bird droppings provide nutrients, especially
  nitrogen, to the fungus
• Symptoms similar to tuberculosis (identify by
  microscopic exam of sputa serologic tests)

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Obstructive lung diseases

• Cystic fibrosis
• Cancer
• Aspiration pneumonia
• COPD (chronic obstr. pulm. dis)
• - Emphysema
• - Chronic bronchitis
• - Bronchial asthma
• - bronchiectasis

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Bronchial Asthma

• Asthma is a condition characterized by reversible
  bronchospasm and chronic inflammation of airway
  passages.
• The incidence of asthma has been steadily
  increasing in recent years.
• Although the exact etiology is still uncertain,
  there appears to be a definite genetic
  predisposition to the development of asthma.

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Pathogenesis of bronchial ashma.

• A key component of asthma appears to be airway
  hyper reactivity in affected individuals.
  Exposure to certain triggers can induce marked
  bronchospasm and airway inflammation in
  susceptible patients.
• Patients with asthma appear to produce large
  amounts of the antibody IgE that attach to the
  mast cells present in many tissues.

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• Exposure to a trigger such as pollen will result
  in the allergen-binding mast cell-bound IgE,
  which in turn causes the release of inflammatory
  mediators such as Histamine , Leukotrienes and
  Eosinophilic Chemotactic factor.
• The response of a patient with asthma to these
  triggers can be divided into an early phase and
  a late phase.

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• Some Potential Asthma Triggers
• Allergens Pollen, pet dander, fungi, dust
  mites.
• Cold air.
• Pollutants.
• Cigarette smoke.
• Strong emotions.
• Exercise.
• Respiratory tract infections.

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• Early phase of asthma
• The early phase of asthma is characterized by
• marked constriction of bronchial airways
  (bronchospasm)
• edema of the airways
• production of excess mucus.
• The bronchospasm that occurs may be the result
  of the increased release of certain inflammatory
  mediators such as histamine, prostaglandins and
  bradykinin that, in the early stages of asthmatic
  response, promote bronchoconstriction rather than
  inflammation.

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• Early phase of asthma

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• Late phase of asthma
• The late phase of asthma can occur several hours
  after the initial onset of symptoms and manifests
  mainly as an inflammatory response.
• The primary mediators of inflammation during the
  asthmatic response are the white blood cells
  Eosinophils that stimulate mast cell
  degranulation and release substances that attract
  other white cells to the area.

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• Subsequent infiltration of the airway tissues
  with white blood cells such as Neutrophils and
  lymphocytes also contributes to the overall
  inflammatory response of the late phase of asthma.

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Clinical Classification of Asthma

• Mild intermittent Attacks occur 2 times per
  week or less
• Mild persistent Attacks occur more than 2 times
  per week
• Moderate persistent Attacks occur daily or
  almost daily and are severe enough to affect
  activity
• Severe persistent Attacks are very frequent and
  persist for a long period of time attacks
  severely limit activity

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• Manifestations of asthma
• Coughing, wheezing
• Difficulty breathing
• Rapid, shallow breathing
• Increased respiratory rate
• Excess mucus production
• Significant anxiety

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• Staging of the Severity of an Acute Asthma Attack
• Stage I (mild)
• Mild Dyspnea
• Diffuse wheezing
• Adequate air exchange
• Stage II (moderate)
• Respiratory distress at rest
• Marked wheezing
• Stage III (severe)
• Marked respiratory distress
• Cyanosis
• Marked wheezing or absence of breath sounds
• Stage IV (respiratory failure)
• Severe respiratory distress, lethargy, confusion,
  prominent pulsus paradoxus

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• Possible complications of asthma can include
• 1- Severe acute Asthma (status asthmatics), which
  is a life-threatening condition of prolonged
  bronchospasm that is often not responsive to drug
  therapy.
• 2- Respiratory failure marked hypoxemia and
  acidosis might occur.

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• 3- Pneumothorax is also a possible consequence
  as a result of lung pressure increases that can
  result from the extreme difficulty involved in
  expiration during a prolonged asthma attack.

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• Treatment of asthma
• The treatment regimen for asthma is based on the
  frequency and severity of the asthma attacks
• 1. Avoidance of triggers, and allergens. Improved
  ventilation of the living spaces, use of air
  conditioning.
• 2. Bronchodilators (eg albuterol, terbutaline)
  Short acting ß-Adrenergic receptor activators.
  May be administered as needed in the form of a
  nebulizer solution using a metered dispenser or
  may be given subcutaneously. These drugs block
  bronchoconstriction but do not prevent the
  inflammatory response.

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• 3.Xanthine drugs (example theophylline)
• Cause bronchodilation and also inhibit the late
  phase of asthma.
• These drugs are often used orally as second-line
  agents in combination with other asthma therapies
  such as steroids.
• Drug like theophylline can have significant
  central nervous system, cardiovascular and
  gastrointestinal side effects that limit their
  overall usefulness.

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• 4. Cromolyn sodium
• Anti-inflammatory agent that blocks both the
  early and late phase of asthma. The mechanism of
  action is unclear but may involve mast cell
  function or responsiveness to allergens.
• 5. Anti-inflammatory drugs (corticosteroids)
• Used orally or by inhalation to blunt the
  inflammatory response of asthma.

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• The most significant unwanted effects occur with
  long-term oral use of corticosteroids and may
  include immunosuppression , increased
  susceptibility to infection, osteoporosis and
  effects on other hormones such as the
  glucocorticoids.
• 6. Leukotrienes modifiers (example Zafirlukast)
  
• New class of agents that blocks the synthesis of
  the key inflammatory mediators, leukotrienes.

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Bronchitis

• Bronchitis is an obstructive respiratory disease
  that may occur in both acute and chronic forms.
• Acute bronchitis Inflammation of the bronchial
  passages most commonly caused by infection with
  bacteria or viruses.
• Acute bronchitis is generally a self-limiting
  condition in healthy individuals but can have
  much more severe consequences in individuals who
  are weakened with other illness or who are
  immunocompromised.
• Symptoms of acute bronchitis often include
  productive cough, Dyspnea and possible fever.

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• Chronic bronchitis Chronic bronchitis is a
  chronic obstructive pulmonary disease that is
  most frequently associated with cigarette smoking
  (approximately 90 of cases).
• Chronic bronchitis may also be caused by
  prolonged exposure to inhaled particulates such
  as coal dust or other pollutants.
• Chronic bronchitis sufferers are often referred
  to as blue bloaters as a result of the cyanosis
  and peripheral edema that is often present.

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• The disease is characterized by excess mucus
  production (purulent) in the lower respiratory
  tract. This mucus accumulation can impair
  function of the ciliated epithelium and lining of
  the respiratory tract and prevent the clearing of
  debris and organisms. As a result, patients with
  chronic bronchitis often suffer repeated bouts of
  acute respiratory infection.
• Dyspnea, hypoxia, cyanosis and Symptoms of cor
  pulmonale.
• Fluid accumulation (edema) in later stages

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• Treatment of chronic bronchitis
• 1. Cessation of smoking or exposure to irritants.
• 2. Bronchodilators to open airway passages.
• 3. Expectorants to loosen mucus.
• 4. Anti - inflammatory to relieve airway
  inflammation and reduce mucus secretion.
• 5. Prophylactic antibiotics for respiratory
  infections.
• 6. Oxygen therapy.

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• Bronchiectasis
• It is a condition that results from prolonged
  injury or inflammation of respiratory airways and
  bronchioles.
• It is characterized by abnormal dilation of the
  bronchus or bronchi. It is most frequently
  associated with chronic respiratory disease,
  infections, cystic fibrosis, tumor growth or
  exposure to respiratory toxins.
• The major manifestations of bronchiectasis are
  impaired ventilation of the alveoli, chronic
  inflammation and possible fibrosis of the areas.

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Emphysema

• Emphysema is a respiratory disease that is
  characterized by destruction of the elastic wall
  of alveolar air sacs causing their permanent
  enlargement and damage.

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• Well over 95 of all patients with emphysema were
  chronic cigarette smokers. Although the exact
  etiology of emphysema is still uncertain,
• Chronic exposure to cigarette smoke causes
  chronic inflammation of the alveolar airways,
  which results in infiltration by lymphocytes and
  macrophages.
• Excess release of protease enzymes such as
  trypsin from lung tissues and leukocytes can
  digest and destroy the elastic walls of the
  alveoli.

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• Bullous emphysema Large subpleural
  bullae

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• Levels of a protective enzyme a-1-antitrypsin
  have been shown to be lacking in certain
  individuals who are chronic cigarette smokers.
  This enzyme inactivates destructive protease
  enzymes (trypsin) in lung tissue.
• In fact, a rare form of emphysema occurs in
  individuals who are not cigarette smokers but who
  have a genetic lack of a-1-antitrypsin.

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• Manifestations are caused by Loss of alveolar
  (lung) elasticity and a decrease in the overall
  surface area for gas exchange within the lungs.
• Manifestations include the following
• - Tachypnea (increased respiratory rate) Because
  that is effective in maintaining arterial blood
  gases, one does not usually see hypoxia or
  cyanosis until the end stages of the disease.
• - Barrel chest from prolonged expiration.
• - Lack of purulent sputum.
• - Possible long-term consequences, including cor
  pulmonale , respiratory failure.

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Comparison of Symptoms for Chronic Bronchitis
and Emphysema
Chronic bronchitis Emphysema
Mild Dyspnea Dyspnea that may be severe
Productive cough Dry or no cough
Cyanosis common Cyanosis rare
Respiratory infection common Infrequent infections
Onset usually after 40 years of age Onset usually after 50 years of age
History of cigarette smoking History of cigarette smoking
Cor pulmonale common Cor pulmonale in terminal stages
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Pneumothorax

• Pneumothorax is the entry of air into the pleural
  cavity in which the lungs reside.
• In order for normal lung expansion to occur,
  there must be a negative pressure within the
  pleural cavity with respect to atmospheric
  pressure outside the pleural cavity. The inside
  of the pleural cavity is essentially a vacuum and
  when air enters the pleural cavity the negative
  pressure is lost and the lungs collapse.
• Because each lung sits in a separate pleural
  cavity, pneumothorax of one plural cavity will
  not cause collapse of the other lung.

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Types of pneumothorax

• 1. Open or communicating pneumothorax
• Usually involves a traumatic chest wound.
• Air enters the pleural cavity from the
  atmosphere.
• The lung collapses due to equilibration of
  pressure within the pleural cavity with
  atmospheric pressure.

2. Closed or spontaneous pneumothorax Occurs
when air leaks from the lungs into the pleural
cavity. May be caused by lung cancer, rupture,
pulmonary disease. The increased plural
pressure prevents lung expansion during
inspiration and the lung remains collapsed.
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3. Tension pneumothorax A condition in which
there is a one-way movement of air into but not
out of the pleural cavity. May involve a hole
or wound to the pleural cavity that allows air to
enter and the lung to collapse. Upon expiration,
the hole or opening closes, which prevents the
movement of air back out of the pleural cavity.
A life-threatening condition because pressure in
the pleural cavity continues to increase and may
result in further lung compression or compression
of large blood vessels in the thorax or the
heart.
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• Manifestations of pneumothorax
• Tachypnea, Dyspnea
• Chest pain
• Possible compression of thoracic blood vessels
  and heart, especially with tension pneumothorax
• Treatment of pneumothorax
• Removal of air from the pleural cavity with a
  needle or chest tube
• Repair of trauma and closure of opening into
  pleural cavity

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Restrictive Pulmonary Disorders

• Abnormalities of chest wall which limits lung
  expansion
• - Kyphosis
• - Scoliosis
• - Polio
• - Atelectasis
• - Muscular dystrophy
  
• Disease affecting lung tissue that provides
  supporting framework
• - Occupational diseases (pneumoconioses)
• - Idiopathic pulmonary fibrosis (autoimmune
  disease)
• - Pulmonary edema
• - Acute respiratory distress syndrome (ARDS)

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Atelectasis

• Atelectasis is a condition in which there is
  incomplete expansion of lung tissues due to
  blockage of the airways or compression of the
  alveolar sacs.
• Types of atelectasis
• 1. Absorption atelectasis
• Results when the bronchial passages are blocked
  with mucus, tumors or edema
• May occur with conditions such as chronic
  bronchitis or cystic fibrosis in which there is
  the accumulation of excess mucus in the
  respiratory passages
• 2. Compression atelectasis
• Occurs when lung tissue is compressed
  externally by air, blood, fluids or a tumor

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• Manifestations of atelectasis
• Dyspnea, cough.
• Reduced gas exchange.
• Shunting of blood to areas of the lungs that
  are inflated. The ventilation perfusion coupling
  ability of the lungs will help ensure that blood
  is directed to areas of the lungs where gas
  exchange can still occur.

• Treatment of atelectasis
• Removal of airway blockage
• Removal of air, blood, fluids, tumors, etc.
  that are compressing lung
• tissues

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• Pneumoconiosis
• Def occupational diseases from inhaling
  inorganic dust particles
• over a long time period (10 years
  or greater)
• Pathophysiology
• Get inflammation fibrosis
• This destroys the connective tissue framework of
  lungs
• Lung compliance is lost
• Of all the causes, asbestosis is worst
• Also gives one pleural fibrosis lung cancer
• Sx
• First to appear is dyspnea on exertion
• Eventually get pulmonary hypertension

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• Types
• Anthracosis black lung disease from coal dust
  (carbon)
• Asbestosis from asbestos fibers, most common
  form
• Berylliosis from beryllium dust
  (semiconductors)
• Silicosis from silica dust (quartz dust) e.g.
  stone quarries

Asbestos bodies in lung
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Adult respiratory distress syndrome (ARDS)

• ARDS is a syndrome associated with destruction of
  alveolar membranes
• and their related capillaries. It may occur as a
  result of direct injury to the lungs or as a
  result of dramatic decreases in blood flow to the
  lung (shock lung) .

148
Possible Causes of ARDS

• Septicemia, uremia
• Trauma
• Near drowning
• Inhalation of toxic gases or agents
• Aspiration of gastric contents
• Widespread pneumonia
• Drug overdose
• Systemic shock

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Manifestations of ARDS

• Dyspnea, tachypnea.
• Hypoxemia CO2 is significantly more water
  soluble than O2 and can still be eliminated from
  the lungs via diffusion as a result blood levels
  of oxygen are more affected by ARDS than CO2.
  Hypocapnia may result.
• Infiltration of lung tissues with immune cells
  that release inflammatory mediators.
• Accumulation of fluids in alveoli and around
  alveolar spaces.
• Changes in blood pH due to altered blood levels
  of CO2.
• Pulmonary fibrosis.
• Respiratory failure.

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Treatment of ARDS

• Oxygen therapy
• Anti-inflammatory drugs
• Diuretics to reduce edema
• Correction of acidbase balance

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Respiratory distress syndrome of the newborn

• The etiology of newborn respiratory distress
  syndrome differs considerably from that of the
  adult disorder.
• Respiratory distress in the newborn is most
  commonly caused by a lack of surfactant in the
  lungs.
• Pulmonary surfactant is a mixture of lipids and
  proteins produced by Type II cells of the
  alveoli.
• A thin layer of surfactant covers the surfaces of
  the alveoli and provides surface tension that
  prevents the thin-walled alveoli from collapsing.
  

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• Surfactant also moistens the alveolar surfaces to
  facilitate gas exchange.
• Respiratory distress syndrome of the newborn
  occurs most commonly in infants who are born
  prematurely and whose lungs have not developed to
  the point where they are producing adequate
  surfactant.
• Clinical manifestations become evident
  immediately at birth and can be rapidly fatal if
  not treated.

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Manifestations

• Rapid, shallow breathing
• Lung collapse
• Lung inflammation and damage
• Hypoxemia
• Nasal flaring, grunting upon inspiration

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Treatment

• 1- Delay or prevention of premature delivery of
  infant if possible.
• Treatment of premature newborn with synthetic
  surfactant delivered directly into the lower
  respiratory tract. Exogenous surfactant will need
  to be supplied until the infants lungs have
  matured to the point where they are producing
  their own surfactant.

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• Mechanical ventilation.
• Injection of cortisol in the mother prior to
  delivery may significantly reduce the incidence
  of respiratory distress syndrome in premature
  infants.
• Cortisol has also been shown to stimulate
  activity of Type II cells.

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• Vascular disorders

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• Pulmonary edema
• Pathophysiology
• Fluid collection (edema) in all lung tissues
• Affects gas exchange
• Affects lung expansion
• Key pulmonary capillary pressure increases
  fluid moves into alveoli
• Capillaries rupture get bloody sputum
  (hemoptysis)
• True medical emergency
• Etiology
• Left sided heart failure
• Hypoproteinemia
• Inhalation of toxic gases
• Lymphatic blockage (e.g. from tumor)

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• Pulmonary Emboli
• def clot of foreign matter that occludes artery
  in pulmonary system
• Size of embolus general health of patient
  determine degree of damage and amount of symptoms
  
• see next slide for pathophysiology
• etiol
• determined by composition of emboli
• thrombus (most common) , air, fat, bacteria,
  tissue
• risk increased by CHF, lung disease, stasis with
  varicosities
• 90 originate from deep veins (primarily in leg)
• Old age large bone fractures give fat emboli

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• Sx
• generally apprehension, cough, chest pain, fever
• if severe ------ dyspnea, tachypnea, hemoptysis
• if massive ----- shock death
• Dx imaging, blood gases
• Tx
• maintain adequate ventilation via O2
  anticoagulants
• ? Thrombolytic drugs
• Prevention via early ambulation, TED Stockings

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Pathophysiology of pulmonary embolus
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• Lung Cancer
• leading cause of cancer deaths in both men
  woman in US
• 4 cell types
• Oat Cell (2) Squammous Cell (3)
  AdenoCa (4) large cell
• Pathophysiology
• Most arise from bronchi or bronchioles

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• Squamous cell from large bronchi at hilus of lung
• Slow growing late metastasis
• Adenocarcinoma (bronchoalveolar)
• Found in periphery
• Present frequently with pleural effusion
• Moderate growth rate
• Oat cell (small cell)
• Found centrally near large bronchus
• Fast growing early metastasis
• Large cell (undifferentiated)
• Rapid growth early metastasis
• Found in periphery thus get pleural effusion

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• Effects from lung cancer
• Obstruction
• Inflammation
• Pleural effusion
• Paraneoplastic syndrome
• The tumor cells secrete hormone-like substances
• ADH ACTH

• Squamous cell lung cancer

165
Squamous cell cancer
Oat cell cancer
Adenocarcinoma
Large cell cancer
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Respiratory Failure

• Respiratory failure is a condition that results
  when the lungs are no longer able to oxygenate
  the blood sufficiently or remove CO2 from it.
• It may occur as
• the end result of chronic respiratory diseases,
  or it may be an acute event caused by factors
  such as neumothorax or Opioid drug overdose

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Manifestations of respiratory failure

• Hypoxemia.
• Hypercapnia
• Cyanosis, possible but not always present.
• Central nervous system symptoms Slurred
  speech, confusion, impaired motor function
• Altered blood pH
• Initial tachycardia and increased cardiac
  output followed by bradycardia and decreased
  cardiac output

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Causes of Respiratory Failure

• B) Chronic
• Emphysema
• Interstitial lung diseases
• Cystic fibrosis
• Spinal cord or brain injury
• Congestive heart failure
• Neuromuscular disorders Muscular dystrophy,
  myasthenia gravis, amyotrophic lateral sclerosis
• Pulmonary emboli
• Diffuse pneumonia
• Pulmonary edema

• A) Acute
• Pneumothorax
• Drug overdose (opioids, sedatives)
• Pleural effusion Accumulation of fluids in the
  pleural cavity
• Airway obstruction
• Status asthmaticus
• Inhalation of toxins or noxious gases.

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• Treatment of respiratory failure
• Bronchodilators
• Correction of blood pH
• Oxygen therapy
• Mechanical ventilation

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Respiratory Pathophysiology243 RTS

• Prepared by
• Dr. Taghrid M. Abdallah.
• Dr.Taghrid_at_Inaya.edu.sa