Asthma and broncho-hyperresponsiveness PBL NOTES

1) Revise the principle of alveolar-capillary gas exchange

  • Deoxygenated blood reach alveoli by pulmonary circulation

  • Oxygenated blood returns to left side of heart

  • CO2 released in blood in capillaries to be exhaled

2) Revise the commonly measured parameters of pulmonary function tests and their clinical uses

  • FVC: indicator of lung size + capacity = max air forcefully exhaled after taking a deep breath

  • PFT: non-invasive spirometry-based tests that measures lung function + supports diagnosis

  • FEV1: amount of air forcefully exhaled after first second

  • FEV1/FVC: to diagnose obstructive and restrictive lung disease

  • Total Residual Volume (TRV) (6L) - amount of air remained in lungs after maximal expiration

    • Increased in obstructive due to airway narrowing

  • Total lung capacity (TLC) - total volume of air in lungs after a maximal inspiration

    • Increased in obstructive due to increased residual volume

    • Decreased in restrictive due to failure of lung expansion

3) Recognize the pathophysiology of restrictive and obstructive lung diseases and how they are diagnosed

  • Restrictive: can't fully expand lungs, lungs cannot be fully filled with air → reduced FDV and a FEV1

    • Intrinsic: problems with alveoli + interstation (other fluid)

      • e.g. pulmonary fibrosis, sarcoidosis (inflammation of lungs, macrophages surrounding a foreign object such as bacteria to stop it from spreading)

    • Extrinsic: diaphragm, muscles, pleura, chest wall

      • Pleural effusion, spinal scoliosis (deviation of normal spine curvature)

Result in decreased elasticity of the lungs or difficulty in expansion of lungs

  • Obstructive: airway narrowing causes problems with exhaling the air

    • Air is exhaled at a slower rate and higher residual volume after exhalation

Diagnosis:

  • FEV1:FVC

    • If under 80% = Obstructive (FEV1 affected more)

    • If above 80% = Restrictive (FVC affected more)

4) Pathophysiology of bronchial hyper-responsiveness in asthma

  • Bronchial hyper-responsiveness (Asthma): exaggerated bronchiole constrictor response to bronchiole inhaled stimuli

  • Cause: large amounts of IGE antibodies reacting with specific antigens

    • IGE is attached to mast cells near bronchioles

  1. IGE reacts with antigen → degranulation of mast cells → releases histamine → histamine acts on histamine 1 receptors on bronchiole smooth muscle cells → bronchoconstriction

  2. IGE also bind with eosinophils → release of eosinophilic chemicals → activation of cholinergic pathway → increased ACh release from parasympathetic neurons that innervate the airways → smooth muscle contraction + bronchoconstriction

  3. Inflammatory markers including IL-1 + TNFa released by T-lymphocytes → inflammation → Obstruction → bronchoconstriction

  4. Inflammation releases bradykinin → bronchoconstriction in two ways:

    • Indirect: Activates thromboxane A2 → activates cholinergic pathway → ACh → smooth muscle contraction → bronchoconstriction

    • Direct: direct activation of cholinergic pathway

  • All leads of airway narrowing and increased restriction

5) Mechanisms of arterial blood gas abnormalities in asthma

  • Low O2 and high CO2 and low HCO3- → activates peripheral and central chemoreceptors

  • Activation of receptors leads to activation of respiratory system

    • increased RR and depth of ventilation (hyperventilation)

  • HCO3- binds with H+ to form CO2 to be exhaled → HCO3- is low

    • asthma = respiratory acidosis without any buffer

  • Low O2 due to impaired gas exchange

6) Physiological significance of ventilation-perfusion relationship and how V/Q mismatch is brought about and how the lungs compensate to correct pathological V/Q mismatch

  • V/Q - displays the efficiency of the air reaching alveoli and the flow of blood in capillaries

  • low V/Q - result of perfusion of poorly ventilated alveoli due to obstruction

    • asthma

    • COPD

  • high V/Q - result of ventilation of poorly perfused alveoli; not enough blood coming in and reaching capillaries

    • Pulmonary oedema

  • Compensation:

    • Low V/Q

      • Hypoxic vasoconstriction: when V/Q ratio is more blood and less air, results in directing the blood from the hypoxic areas to other areas → decreasing the perfusion of hypoxic regions + increasing V/Q ratio

    • High V/Q

      • Bronchoconstriction: when V/Q ratio is high there is more air and less blood, results in bronchoconstriction to reduce the volume of air that reaches the under perfused regions → correcting the V/Q ratio

7) Understand the pathogenesis of reversible and irreversible obstructive lung diseases along with their diagnosis

  • Reversible: asthma bronchial hyper-responsiveness

  • Irreversible: COPD

    • Definition: chronic airway narrowing/inflammation + tissue destruction → chronic airway obstruction + remodeling; results in the irreversibility of the disease

    • Pathogenesis:

            a) Smoking ciggarretes → Activation of immune system in airways → release of proinflammatory cytokines + chemotactic factors → increased recruitment of neutrophils, macrophages, cytoxic, helper T cells, and proteases (results in remodeling) → inflammation of bronchi + structural changes to parenchyma → chronic bronchitis and emphysema

            b) Inflammation lead to goblet cell proliferation → increased mucus production → impaired ciliary function → recurrent infection → bronchitis

  • Both lead to airway obstruction

  • Diagnosis: based on measurements of reversibility of bronchoconstriction by a bronchodilator challenge (spirometry based)

  • Irreversible (COPD): minimum reversal of airway narrowing post bronchodilator challenge

  • If FEV1 is higher than 12% = reversible

  • If FEV1 is lower than 12% = irreversible

8) Contrast the effects of reversible and irreversible obstructive lung diseases on the heart and pulmonary circulation

  • Irreversible right side of heart

    • Chronic airway narrowing → alveolar hypoxia (decreased V/Q) → hypoxic pulmonary vasoconstriction → increased right ventricular afterload → increased right ventricular pressure + volume → increased right ventricular enlargement + hypertrophy → tricuspid valve stretch → regurgitation of blood in right atrium → increased right atrial pressure + volume → atrial enlargement → increased CVP + JVP → murmur + right side heart failure

  • Reversible :

    • increased histamine (vasodilator) → decreased systemic BP + increased HR (compensatory mechanism)

    • short term

    • rare to occur

    • less effect on heart and lungs due to acute hypoxic vasoconstriction