Pulmonary Pathophysiology III

Iain MacLeod, Ph.Dimacleod@hsph.harvard.edu

Iain MacLeod 16 November 2009

Review – Pulmonary II - Obstruction

Should be a well-understood concept that when an airway narrows its resistance greatly increases

Airway resistance, and thus obstruction, can be easily measured by determining the FEV1 / FVC ratio.

The FVC is measured by having a person take in as much air as they possibly can and then breathe out as

much as they can into a spirometer, until no more air will come out. The total amount of air that they

breathe out is the FVC. The FEV1 is the amount of air that comes out in the first second. The technique has

the advantage of being mostly effort independent.

A value less than 80% indicates that an airway obstruction may be present

Review – Pulmonary II - Asthma

Review – Pulmonary II - Asthma

FEV1/FVC is greatly reduced during an attack – why ?

Review – Pulmonary II - Asthma

FEV1/FVC is greatly reduced during an attack – why ?

• Bronchoconstriction

- Airway hyperresponsiveness: increased airway narrowing in response to contractile

agonists that have little if any effect in normal subjects

histamine, methacholine, leukotrienes – can be diagnostic using the PD20

Review – Pulmonary II - Asthma

FEV1/FVC is greatly reduced during an attack – why ?

• Bronchoconstriction

- Airway hyperresponsiveness: increased airway narrowing in response to contractile

agonists that have little if any effect in normal subjects

histamine, methacholine, leukotrienes – can be diagnostic using the PD20

• Inflammation

- Mediated mainly by lymphocytes (CD4 and CD8 T cells) and eosinophils.

IL-5 Granules

IgE Diffusion & Contraction

Allergy

Review – Pulmonary II – Asthma & Allergy

Review – Pulmonary II – Asthma Treatment

What do each of these do ?

• Corticosteroids

• -agonists

• Leukotriene Synthesis Inhibitors

• Omalizumab

Review – Pulmonary II – Asthma - Influencing Factors

Nature vs. Nurture

- genetic factors involved in IgE synthesis

- exposure to viruses / allergens / cigarette smoke

Why is asthma on the increase?

- hygiene hypothesis

- obesity

- allergens

- pollution

Review – Pulmonary II - COPD

Emphysema and Chronic Bronchitis

Review – Pulmonary II - COPD

Emphysema and Chronic Bronchitis

• destruction of alveolar wall and capillary bed but without obvious scarring (fibrosis).

• enlarged air spaces

• small airways are narrowed, thin walled, may be reduced in number

• pan acinar - central part of acinus (respiratory bronchioles mainly affected)

• pan lobular whole acinus afflicted‑

• apex of lung most often affected first

• increased pulmonary compliance (elastase)

• hypertrophy of mucus glands

• goblet cell metaplasia

• inflammation in small airways and in glands

• mucus in airways, sometimes occluding airway lumen

• airway wall edema

• thickened epithelium

Review – Pulmonary II – COPD - Emphysema

Inhaled toxins trigger local inflammation

in alveoli

Inflammatory mediators cause the

destruction of alveolar septum – decrease

in surface area available for gas exchange

Additional destruction of capillaries that

serve alveoli.

Ventilation/ Perfusion inequality – some areas of the lung could receive large quantities of air but have

insufficient blood flow (or vice versa).

Lower PaO2 but normal PaCO2 (although PaCO2 will rise once disease becomes extensive)

Review – Pulmonary II – COPD - Emphysema

How does emphysema lead to pulmonary hypertension ?

- as disease progresses and high enough PaO2 cannot be reached, the body compensates through

vasoconstriction.

- the heart tries to provide more blood to the lungs in order for PaO2 to increase, leading to thickening of

the heart muscle. Eventual heart failure ensues.

What role does 1 anti-trypsin play? (Discuss)