Respiratory System -

Pathophysiology

Core Biomedical Science

 Percent Change in Age-
Adjusted Death Rates, U.S.,
1965-1998
Proportion of 1965 Rate
3.0
Coronary Stroke Other CVD COPD All Other
2.5 Heart Causes
Disease
2.0

1.5

1.0

0.5
–59% –64% –35% +163% –7%
0
1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998 1965 - 1998
Causes of pulmonary disease
Impaired ventilatory Airway obstruction
regulation (e.g. drugs) (e.g. asthma)

Loss of respiratory Lung restriction

interface (e.g. (e.g. fibrosis)
emphysema)
Lung cancer
Muscle deficiency Diffusion impairment
(e.g. muscular (e.g. oedema)
dystrophy)

Heart failure
(esp. left side)
 Chronic Emphysema
Asthma
bronchitis

Reversibility

Sputum
production

Alveolar
damage
 Asthma - Definition
“A chronic lung disease characterised by inflammation
of the lower airways causing airflow obstruction, which
is recurrent and reversible.”

• chronic inflammatory disorder of the airways in which many cells

play a role - in particular mast cells, eosinophils, and T-
lymphocytes
• recurrent episodes of wheezing, breathlessness with airflow
limitation that is at least partly reversible either spontaneously or
with treatment
• reversible disease (symptoms) but potentially can become
irreversible (permanent airway scarring/remodelling)
leading to a chronic obstructive pattern if long-standing
& inadequately controlled
 Asthma - Statistics
• 5% of adult population (remission less common)
• 7 to 10% of children (many outgrow this condition)
• 50% of cases develop in childhood
• 30% of asthmatics recover before adolescence
• In the US, 26.7 million people (96.6/1000 population)
diagnosed with asthma, of which 11.1 million persons
experienced at least one exacerbation
• From 1980-2001: number of GP visits for asthma as the
primary diagnosis increased from 5.9 million to 10.8 million
• In 2001: approx 0.5million hospitalizations in the US; 4657
asthma related deaths in the same year
Clinical Symptoms of Asthma
• Dyspnoea
• Cough
• Wheezing
Risk factors
• Gender • Genetic factors
• Allergen (more common in e.g. twin studies
exposure boys than girls)
(sensitization)
• Race
• House-dust mite
allergens
Asthma e.g. Maoris high
and Aborigines
low

• Passive
smoking
• Outdoor air • Diet
pollutants
 Asthma - Causes
asthma sufferers

• born genetically susceptible to asthma

• but it takes a trigger to cause the attack
 Pathogenesis INDUCERS
Allergens,Chemical sensitisers,
Airway Air pollutants, Virus infections
Hyper-responsiveness
Genetic

INFLAMMATION
Airflow Limitation

TRIGGERS
Allergens, Exercise, SYMPTOMS
Cold Air, SO2 Particulates Cough Wheeze
Dyspnoea
 Asthma - Types
Extrinsic (Immune Antigens)
Atopic Asthma - Most Common
(Type I hypersensitivity)
Asthma

Intrinsic (Non-Immune)
Non-atopic Asthma
Aspirin Exercise
Cold ( temp) Irritants
Stress Pollutants
Extrinsic (Atopic Asthma)

• most common type of asthma

• first two decades of life
• serum IgE 
• blood eosinophil count 
 Extrinsic (Atopic Asthma)
Eosinophils release inflammatory mediators
responsible for increased bronchial
inflammation and produce a major basic
protein that:

a. stops ciliary beating

b. disrupts mucosal integrity
c. causes damage & sloughing of
epithelial cells
 Asthma - Micropathology

• Oedema, hyperaemia, & inflammation of

bronchioles
• Eosinophils > mast cells;
lymphocytes (CD4)
• Patchy necrosis
 Asthma - Morphologic
Pathology
Mucus plugs in bronchi & bronchioles
 Asthma - Morphologic
Pathology
Charcot - Leyden crystals
- breakdown products of eosinophils
Asthma pathology

Hyperinflated lungs of a patient who died with status

asthmaticus.
 Asthma - Treatments
Two main forms of treatment:
Preventers
• Corticosteroids
– Soft Steroids
– Anti-inflammatory

• Mast Cell Stabilisers

– Cromoglycates
– stabilize membrane - reduce calcium influx

Relievers
• β2 adrenoreceptor agonists
- e.g.salbutamol/ventolin
- bronchodilators
- mainstay of current drug therapy

• Leukotriene receptor antagonists – anti-inflammatory

 Emphysema
• destruction of alveolar walls - below the
bronchioles
• decreases surface area available for
gas exchange
• increases resistance to pulmonary
blood flow
Emphysema
Two types - panacinar & centrilobular
emphysema

normal
 Emphysema: Incidence
• 50% of autopsy patients
• most asymptomatic
• centriacinar (respiratory bronchioles) more common
• more severe in men than women
• !! SMOKING !!
 Emphysema - effects
• lungs can not recoil and air is trapped - inflation
• residual lung capacity increases
• pO2 decreases over time - reduced saturation of
haemoglobin
• pCO2 can increase over time - increased
acidosis
• increased RBC - polycythaemia - high PCV
(haematocrit) – increased risk of thrombosis
 Emphysema - effects
• Also:
• enlarged accessory muscles
• clubbing of fingers
• pursed lips- prolonged expiration-
• wheezing - indicative of obstruction
• decreased FEV1/FVC