26/02/2015

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

2015

How do we breathe in?

Mechanics of breathing

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

Clinical alterations
Surfactant
Alveoli collapse
lung expansion
WOB
Creates severe gas exchange abnormalities

Examples: Cigarette smoking, fresh water

drowning, Neonates (RDS)

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

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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Clinical alterations

Factors determining airway resistance

Asthma

Number of interactions between the

flowing gas molecules

Oedema

Length of airway

Obstruction

Airway radius

Bronchoconstriction = Airway resistance

Compliance

Compliance

Normal expanding pressures of the lungs are:

-2 to -10 cmH2O

The stretchability, distensibility or elasticity of

the lungs & thorax

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

Can be expressed as the volume change per

unit of pressure change

C = V
P

5. Lung Function Measurements

Clinical Alterations
Compliance
Age
COAD

Compliance
Pulmonary fibrosis,
oedema
Pneumonia
ARDS, NRDS, Trauma
Kyphosis, Scoliosis,
Muscular dystrophy
Obesity, Post-op
surgical splinting
Oxygen toxicity

Tidal Volume (VT):

Minute Volume (MV):
Inspiratory Reserve Volume:
Expiratory Reserve Volume:
Residual Volume:
Inspiratory Capacity:
Functional Residual Capacity:
Vital Capacity:
Total Lung Capacity:

500ml
6000ml
3000ml
1100ml
1200ml
3500ml
2300ml
4600ml
6000ml

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OXY-Hb Dissociation Curve

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)

Shift to the right

Clinical applications

Depicts Hbs decreased affinity for oxygen

Ventilatory failure

Caused by:

Metabolic acidosis

PCO2
[H+] / pH
Temperature
2,3 DPG

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

HYPOXIA
An inadequate supply of oxygen to the
tissues.

Metabolic alkalosis
Respiratory alkalosis

EFFECTS OF HYPOXIA IN THE LUNG

The inability of the body to use the

oxygen that is present

CELLULAR CONSEQUENCES

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).

Altered cell function and structure

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

Intracellular dysfunction

DIRECT EFFECTS OF HYPOXIA ON

CELLS
Anaerobic metabolism
Produces ATP to meet the energy requirements
of the body

Disruption of oxygen dependent metabolism

Biochemical disruption

CELL DEATH

HYPERCAPNIA
An accumulation of carbon dioxide in
the blood
Decreased tissue and cellular function

This emergency pathway produces:

Pyruvate & H+

Stimulation of the sympathetic nervous

system

These two substances react with each

other to form Lactic Acid

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

ASTHMA

Results in:
cerebral vasodilation, increased cerebral blood
flow, raised ICP

BRONCHIAL ASTHMA
Chronic disorder of the airways causing
episodes of airway obstruction, bronchial
hyper-responsiveness and airway
inflammation (reversible).
Inflammation
Increased mucus production
bronchoconstriction

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.

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

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

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

T lymphocytes are thought to be involved.

>TH2 cells

EXTRINSIC (ATOPIC) ASTHMA

MECHANISM OF RESPONSE

Airborne allergens involved include:

Dust mites, cockroach, animal dangers, the fungus Alternaria

MECHANISM OF RESPONSE

Early or Acute phase

Late Phase
Develops 4-8 hours after exposure

Initial allergen response

Inflammation and airway responsiveness

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.

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.

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.

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

CHRONIC OBSTRUCTIVE
LUNG DISORDERS
COAD/ COPD

Inhaled corticosteroid [MDI]

Long acting bronchodilators (B2 adrenergic agonist)
Anti-inflammatory agents
Nedocromil (Tilade R)

Theophylline (nocturnal relief)

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

EMPHYSEMA

COAD/COPD
COPD

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

Emphysema

Chronic
Bronchitis

May have overlapping features of

both disorders

Pathophysiology

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

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)

CHRONIC BRONCHITIS
Airway obstruction of the major and small airways
Seen most commonly in middle-aged men

Emphysema
lung tissue

CHRONIC BRONCHITIS
Hypersecretion of mucus in the large airways,
associated with hypertrophy of the submucosal
glands in the trachea and bronchi.

Associated with chronic irritation from smoking

and recurrent infections.

Marked in goblet cells and excess mucus

production with plugging of the airway lumen,
inflammatory infiltration, and fibrosis of the
bronchiolar wall.

Diagnosis based on chronic productive cough for at

least 3 consecutive months in at least 2 consecutive
years.

Thought to be protective responses to tobacco

smoke and other pollutants.

Chronic cough with a gradual in acute

exascerbations, purulent sputum

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.

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

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

ACUTE BACTERIAL PNEUMONIA

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

Bronchopneumonia (patchy consolidation

involving more than one lobe)

HOSPITAL ACQUIRED PNEUMONIA

Lower respiratory tract infection that was not
present or incubating on admission.
Second most common cause of hospitalacquired infection.
Has a mortality rate of 20-50%.
Those at risk include:
Ventilated patients
Compromised immune function
Chronic lung disease
Airway instrumentation (tracheotomy)

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.

Air separates the visceral and parietal pleura

and thus destroys the negative pressure of the
pleural space.

Pneumothorax

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

Present in these two forms

Occurs unexpectedly in healthy individuals,

most often caused by spontaneous rupture of
blebs (blister-like) on visceral pleura.

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.

Secondary Pneumothorax

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

bullet wounds, or surgical procedure; rupture
of large bleb or bulla in COPD.

RESPIRATORY
FAILURE

RESPIRATORY FAILURE
Respiratory failure exists as a
consequence of acutely impaired
respiratory function,
Because the;
Lungs fail to oxygenate arterial blood

DIAGNOSTIC PICTURE
Hypoxaemia
Arterial PO2 < 60 mmHg

Hypercapnia
Arterial CO2 >60

Lungs prevent CO2 Elimination

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Causative Mechanisms

THREE MECHANISMS
Pulmonary failure

THE END RESULT OF THESE

PROCESSES IS CELLULAR
HYPOXIA...

Inadequate oxygen transport

Ineffective cellular use of oxygen

OTHER FACTORS
Increased oxygen demands
Thyroid disease
Extreme exercise
Extreme stress

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