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Respiratory Pathophysiology

NUR5703 Advanced Pathophysiology & Health Assessment 1 Md. Nadim Rahman 2015

Mechanics of breathing How do we breathe in?

Active process that requires

Neural stimulus via phrenic nerve

Muscle activity

Diaphragm

External intercostal muscles

Accessory muscles

Pressure gradients

How do we breathe out?

Passive process

Muscles of expiration

Abdominal muscles

Internal intercostals

Diffusion of gases through the respiratory membrane

The respiratory membrane consists of

(1) A thin layer of fluid lining the alveolus,

(2) The alveolar epithelium comprised of simple squamous epithelium,

(3) The basement membrane of the alveolar epithelium,

(4) A thin interstitial space,

(5) The basement membrane of the capillary endothelium, and the capillary endothelium comprised of simple squamous epithelium

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Factors influencing rate of gas diffusion

(1) The thickness of the membrane,

(2) The diffusion coefficient of the gas in the substance of the membrane.

(3) The surface area of membrane, and the partial pressure difference of the gas between the two sides of the membrane.

Surface Tension

Lungs have a tendency to recoil or collapse due to 2 factors

Elastic fibers

Surface Tension

Surface tension occurs at any gas - liquid interface

Results in the tendency for liquid molecules that are exposed to air to adhere to one another

Surfactant

A lipoprotein secreted by Type II cells in alveoli

Reduces the surface tension of the fluid lining alveoli

Advantages:

compliance

reduces WOB

stabilizes alveoli

keeps alveoli dry

Clinical alterations

Surfactant

Alveoli collapse

lung expansion

WOB

Creates severe gas exchange abnormalities

Examples: Cigarette smoking, fresh water drowning, Neonates (RDS)

Airway Resistance

The opposition to force within the airways

Volume of airflow is directly proportional to the pressure gradient

Flow of air in and out is inversely proportional to airway resistance

RESISTANCE = PRESSURE FLOW

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Factors determining airway resistance

Number of interactions between the flowing gas molecules

Length of airway

Airway radius

Clinical alterations

Asthma

Oedema

Obstruction

Bronchoconstriction = Airway resistance

Compliance

The stretchability, distensibility or elasticity of the lungs & thorax

Can be expressed as the volume change per unit of pressure change

C = V

P

Compliance

Normal expanding pressures of the lungs are: -2 to -10 cmH2O

Provides an indication of the ease of stretch in relation to the elastic recoil of the lung tissue and the surface tension of the lung

Clinical Alterations

Compliance

Age

COAD

Compliance

Pulmonary fibrosis, oedema

Pneumonia

ARDS, NRDS, Trauma

Kyphosis, Scoliosis, Muscular dystrophy

Obesity, Post-op surgical splinting

Oxygen toxicity

5. Lung Function Measurements

Tidal Volume (VT): 500ml

Minute Volume (MV): 6000ml

Inspiratory Reserve Volume: 3000ml

Expiratory Reserve Volume: 1100ml

Residual Volume: 1200ml

Inspiratory Capacity: 3500ml

Functional Residual Capacity: 2300ml

Vital Capacity: 4600ml

Total Lung Capacity: 6000ml

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Oxygen - haemoglobin dissociation curve

Shows the relationship between dissolved oxygen and haemoglobin bound oxygen

Affected by:

PCO2

Hydrogen ion concentration (pH)

Temperature

2,3-DPG (2,3 diphosphoglycerate)

OXY-Hb Dissociation Curve

Shift to the right

Depicts Hbs decreased affinity for oxygen

Caused by:

PCO2

[H+] / pH

Temperature

2,3 DPG

Clinical applications

Ventilatory failure

Metabolic acidosis

Fever

Septic Shock

Shift to the left

Depicts the Hbs increased affinity for oxygen

Promotes association in lungs

Inhibits dissociation in tissues

Causes by:

PCO2

[H+] / pH

Temperature

2,3 DPG

Therefore: Enhances the affinity of Hb for O2 and

improves oxygen saturations at lower PO2

levels

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Clinical applications

Hypothermia

Metabolic alkalosis

Respiratory alkalosis

HYPOXIA An inadequate supply of oxygen to the

tissues.

The inability of the body to use the oxygen that is present

EFFECTS OF HYPOXIA IN THE LUNG Hypoxia causes the blood vessels of the

pulmonary circulation to vaso-constrict strongly. In localised vasoconstriction this has the effect of directing blood flow away from hypoxic regions of the lung (eg. Atelectasis).

Generalised hypoxia causes vasoconstriction throughout all the vessels of the lung. Generalised vasoconstriction occurs when the partial pressure of O2 drops eg. high altitudes, chronic hypoxia due to lung disease

CELLULAR CONSEQUENCES

Altered cell function and structure

Disruption of oxygen dependent metabolism

Biochemical disruption

Intracellular dysfunction

CELL DEATH

DIRECT EFFECTS OF HYPOXIA ON CELLS

Anaerobic metabolism

Produces ATP to meet the energy requirements of the body

This emergency pathway produces: Pyruvate & H+

These two substances react with each other to form Lactic Acid

HYPERCAPNIA An accumulation of carbon dioxide in

the blood

Decreased tissue and cellular function

Stimulation of the sympathetic nervous system

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CLINICAL MANIFESTATIONS

Depression of the CNS headache papilloedema flapping tremor of hands and arms narcosis Coma

Results in:

cerebral vasodilation, increased cerebral blood flow, raised ICP

ASTHMA

BRONCHIAL ASTHMA Chronic disorder of the airways causing

episodes of airway obstruction, bronchial hyper-responsiveness and airway inflammation (reversible).

Inflammation

Increased mucus production

bronchoconstriction

ASTHMA DEFINITION A chronic inflammatory disorder of the airways

in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, and epithelial cells.

Produces recurrent episodes of airway obstruction, characterised by wheezing, breathlessness, chest tightness, and a cough that is often worse at night and in the early morning.

Usually reversible

Pathophysiology T1H cells differentiate in response to microbes

and stimulates the differentiation of B cells into IgM and IgG-producing plasma cells.

T2H cells on the other hand respond to allergens and helminths by stimulating B cells to differentiate into IgE-producing plasma cells, produce growth factors for mast cells and activate eosinophils.

Cytokines, TNF , IL-4 & IL-5 play roles in the pathogenesis.

TYPES OF ASTHMA Extrinsic asthma Initiated by an extrinsic trigger

Intrinsic asthma Diverse non-immune mechanisms

Respiratory tract infections Exercise Ingestion of aspirin Emotional upset Exposure to bronchial irritants (eg. smoking)

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PATHOGENESIS An exaggerated hypersensitivity response to a

variety of stimuli.

Airway inflammation (manifested by presence of inflammatory cells eosinophils, lymphocytes, mast cells) TNF increases migration and activation of eosinophils and neutrophils

Damage to the bronchial epithelium

T lymphocytes are thought to be involved. >TH2 cells

EXTRINSIC (ATOPIC) ASTHMA

Type 1 hypersensitivity reaction due to exposure to extrinsic antigen or allergen.

Onset is usually in childhood/adolescence

Family history of atopic allergy

Often have other allergic disorders

Airborne allergens involved include: Dust mites, cockroach, animal dangers, the fungus Alternaria

EXTRINSIC (ATOPIC) ASTHMA MECHANISM OF RESPONSE

Early or Acute phase Initial allergen response

Production of mast cells

Symptoms develop within 10-20 minutes

Are due to release of chemical mediators from the

presensitized mast cells

Causes permeability of mucosa, bronchospasm, mucosal oedema.

MECHANISM OF RESPONSE

Late Phase Develops 4-8 hours after exposure

Inflammation and airway responsiveness

Prolongs asthma attack

Starts cycle of exacerbations

Reaches maximum within a few hours and may last days or weeks.

Responsiveness to cholinergic mediators is often

increased.

Chronic inflammation can cause airway remodelling and permanent changes in airway resistance.

INTRINSIC (NONATOPIC) ASTHMA Triggers include;

Respiratory tract infections (esp. Viral),

Exercise,

Hyperventilation,

Cold air,

Drugs and chemicals,

Hormonal changes,

Emotional upsets,

Airborne pollutants and

Gastro-oesphageal reflux.

SEVERE (REFRACTORY) ASTHMA

A subgroup of those with asthma (< 5%) Require high medication use Persistent symptoms despite treatment. Increased risk of fatal or near-fatal attacks

Most deaths occur outside hospital

Those at most risk

Death may be due to cardiac dysrhythmias and

asphyxia due to severe airway obstruction.

Underestimation of severity of attack (unable to recognise the severity of dysnoea)

Lack of access to medical care

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CLINICALLY Diagnosis

Based on clinical and physical examination Respiratory function testing/ spirometry Inhalation testing Peak expiratory flow monitoring over a period of time

Patients may exhibit symptoms spontaneously or triggered by specific event;

Slight chest tightness

Wheezing

Severe respiratory distress

Full Respiratory Arrest

TREATMENT Control of trigger factors

Exposure prevention Relaxation and controlled breathing techniques Desensitisation measures

Pharmacological management Quick relief medications (Acute) B2 Bronchodilators [MDI/Nebs] Relax bronchial smooth muscle

Anticholinergic medications (ipratropium) Block vasoconstriction via efferent Vagal pathways

Corticosteroids to management of inflammation

TREATMENT - PHARMACOLOGICAL MANAGEMENT

Inhalation meds act directly on the large airways to produce bronchodilation. They do not alter the composition or viscosity of mucous.

Long term medications Inhaled corticosteroid [MDI]

Long acting bronchodilators (B2 adrenergic agonist)

Anti-inflammatory agents Nedocromil (Tilade R)

Theophylline (nocturnal relief)

CHRONIC OBSTRUCTIVE LUNG DISORDERS

COAD/ COPD

COPD or COAD

A group of respiratory disorders characterised by chronic and recurrent obstruction of airflow in the pulmonary airways.

The airway obstruction is progressive, may be accompanied by hyper-responsiveness, and may be partially reversible.

Most common cause is smoking (10-15% of smokers will develop the disease)

Condition is well advanced before it becomes symptomatic

COPD Mechanisms

Inflammation and fibrosis of bronchial wall

Hypertrophy of submucosal glands and hyper-secretion of mucus

Loss of alveolar tissue and elastic lung fibres

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COPD Results in obstruction of airflow

Mismatching of ventilation and perfusion.

surface area for gas exchange (alveolar

tissue)

Impaired expiratory flow rate ( elastic fibres)

Increased air trapping

Predisposes to airway collapse

COAD/COPD

COPD

Emphysema

May have overlapping features of both disorders

Chronic

Bronchitis

EMPHYSEMA

Results from breakdown of elastin and other alveolar wall components by enzymes, called proteases, that digest proteins.

Normally the lung is protected by 1-antitrypsin

Cigarette smoke and other irritants stimulate the movement of anti-inflammatory cells into the lungs, resulting in release of elastase and other proteases

Smoking and repeated respiratory tract infections decrease 1-antitrypsin levels

Pathophysiology EMPHYSEMA

Characterised by;

loss of lung elasticity

abnormal enlargement of the air spaces distal to the terminal bronchioles, with

destruction of the alveolar walls and capillary beds.

Enlargement of the alveolar air spaces leads to hyperinflation of the lungs and Total Lung Capacity (TLC)

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Causes:

smoking-incites lung injury

inherited deficiency of 1-antitrypsin (protects the lung from injury) (1% of all COPD cases, more common in young people with emphysema)

Emphysema

lung tissue

CHRONIC BRONCHITIS Airway obstruction of the major and small airways

Seen most commonly in middle-aged men

Associated with chronic irritation from smoking

and recurrent infections.

Diagnosis based on chronic productive cough for at least 3 consecutive months in at least 2 consecutive years.

Chronic cough with a gradual in acute exascerbations, purulent sputum

CHRONIC BRONCHITIS Hypersecretion of mucus in the large airways,

associated with hypertrophy of the submucosal glands in the trachea and bronchi.

Marked in goblet cells and excess mucus production with plugging of the airway lumen, inflammatory infiltration, and fibrosis of the bronchiolar wall.

Thought to be protective responses to tobacco smoke and other pollutants.

Often have viral and bacterial infections.

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PNEUMONIA

PNEUMONIA Inflammation of parenchymal structures of the

lungs (alveoli, bronchioles).

May be due to infection or inhalation (irritating fumes, aspiration of gastric contents)

Classified according to: Type of agent causing infection (typical/atypical)

Distribution of the infection (lobar pneumonia,

bronchopneumonia)

Setting ( community/hospital)

PNEUMONIA

Typical pneumonias results from infection by bacteria that multiply extracellularly in the alveoli and cause inflammation and exudation of fluid into the alveoli

Atypical pneumonias are caused by viral and mycoplasma infections that involve the alveolar septum and interstitium of the lung. They produce less striking symptoms and physical findings that typical pneumonia produce.

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Pathophysiology Pneumococcus remains the most common

cause possessing a capsule of polysaccharide.

The polysaccharide is an antigen that primarily elicits a B cell response with antibody production.

In the absence of antibody, clearance of pneumococci from body relies on the reticuloendothelial system.

Macrophages in the spleen play a major role in antibody production.

ACUTE BACTERIAL PNEUMONIA

Classified as:

Lobar pneumonia (consolidation of part or all of a lung lobe)

Bronchopneumonia (patchy consolidation involving more than one lobe)

COMMUNITY-ACQUIRED PNEUMONIA

Infections from organisms found in the community rather

than in hospitals or nursing homes.

An infection that begins outside the hospital or is

diagnosed within 48 hours of admission in a person who

has not resided in a long-term facility for 14 days or more

before admission.

Most common cause S. pneumoniae

Others include H. Influenzae, S. Aureus, influenza virus, respiratory

syncytial virus, adenovirus

HOSPITAL ACQUIRED PNEUMONIA

Lower respiratory tract infection that was not present or incubating on admission.

Second most common cause of hospital-acquired infection.

Has a mortality rate of 20-50%.

Those at risk include: Ventilated patients

Compromised immune function

Chronic lung disease

Airway instrumentation (tracheotomy)

ACUTE BACTERIAL (TYPICAL) PNEUMONIAS

Most bacteria that cause bacterial pneumonia are normal flora of the oro/nasopharynx and reach the alveoli by aspiration of secretions.

Infection may also be inhaled

Normally these do not cause infection

Infection is due to:

Loss of the cough reflex

Damage to ciliated endothelium

Impaired immune responses

OTHER FACTORS

Antibiotic therapy that alters the normal bacterial flora

Diabetes

Smoking

Chronic bronchitis

Viral infection

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STREP. PNEUMONIAE PNEUMONIA

Most common cause of bacterial pneumonia

Gram +ve diplococci

90 serologically different types

Virulence is due to polysaccharide capsule that prevents or delays digestion by phagocytes.

SYMPTOMS

Vary widely depending on the age and health of the infected person

Previously healthy:

Sudden onset

Characterised by malaise, severe shaking chill, fever

Temperature as high as 41C

Initial stage coughing of watery sputum, limited breath sounds

Progresses to-blood tinged/purulent sputum

Pleuritic pain

THE ELDERLY

In the aged the only sign of pneumonia may be a loss of appetite and deterioration in mental status

ARDS

Mechanisms involved

Barotrauma

Volutrauma

Atelectotrauma

Biotrauma

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Most severe form of Acute Lung Injury

Morbidity 30-60%

Results from

Aspiration

Drugs, Toxins, therapeutic agents

Infections

Trauma & Shock

Disseminated Intravascular Coagulation

Multiple blood transfusions

PATHOGENESIS Pathological lung changes in ARDS are similar

regardless of the precipitating condition. Diffuse epithelial injury

Increase capillary permeability of alveolar-capillary

membrane.

Formation of a hyaline membrane (prevents gas exchange)

Surfactant inactivation

Increase in the intrapulmonary shunt

CLINICALLY

Rapid onset; within 12-18hr of critical event

Increase in work of breathing

Early signs of respiratory failure

Chest xray

Diffuse bilateral infiltrates (as in APO)

No cardiac failure present

Severe hypoxaemia despite oxygen therapy (Refractory)

Often results a systemic response that leads to multiple organ failure.

TREATMENT

Supportive

Ventilation; High PEEP

Improve Oxygenation; Positioning

Aim to improve gas exchange without further lung injury.

Pneumothorax

Air separates the visceral and parietal pleura and thus destroys the negative pressure of the pleural space.

This disrupts the state of equilibrium that normally exists between elastic recoil forces of the lung and chest wall.

No longer held in check, the lung fulfils its tendency to recoil by collapsing toward the hilum.

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Primary Pneumothorax

Occurs unexpectedly in healthy individuals, most often caused by spontaneous rupture of blebs (blister-like) on visceral pleura.

Secondary Pneumothorax

Caused by chest trauma e.g. rib #, stab or

bullet wounds, or surgical procedure; rupture

of large bleb or bulla in COPD.

Present in these two forms

Open (communicating) Pneumothorax: Air pressure in pleural space equals barometric pressure as air that is drawn during inspiration is forced back out during expiration.

Tension Pneumothorax: Acts as a one-way valve, permitting air to enter on inspiration but preventing its escape by closing up during expiration. Its life threatening as pressure exceeds barometric pressure.

RESPIRATORY FAILURE

RESPIRATORY FAILURE

Respiratory failure exists as a consequence of acutely impaired respiratory function,

Because the;

Lungs fail to oxygenate arterial blood

Lungs prevent CO2 Elimination

Hypoxaemia Arterial PO2 < 60 mmHg

Hypercapnia Arterial CO2 >60

DIAGNOSTIC PICTURE

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THREE MECHANISMS

Pulmonary failure

Inadequate oxygen transport

Ineffective cellular use of oxygen

Causative Mechanisms

THE END RESULT OF THESE PROCESSES IS CELLULAR

HYPOXIA...

OTHER FACTORS

Increased oxygen demands

Thyroid disease

Extreme exercise

Extreme stress