Problem 4: Obstructive Diseases II by Lotte van Leeuwen

General Information

lottexvleeuwen — 2020-09-21 11:45:41 UTC

Definition: an obstructive disease, which is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases.'

Both chronic bronchitis and emphysema are included in COPD.
Chronic bronchitis: chronic condition of cough and phlegm.
Emphysema: destruction of alveoli.

Aetiology

lottexvleeuwen — 2020-09-21 11:47:50 UTC

In developed countries it is mostly caused by smoking. only 10-20% of smokers develop COPD, which indicates individual variation.
in developing countries it is mostly caused by atmospheric pollution (e.g. unhealthy cooking environments).

Pathogenesis and pathophysiology: Chronic Bronchitis

lottexvleeuwen — 2020-09-21 13:23:19 UTC

The condition will start off with an irritating cough. In more developed cases there will be green sputum production.

Smoking has reactive oxidants in it, which will cause an immune response and inflammation.
Acute and chronic inflammatory cells infiltrate the walls of the bronchi and bronchioles. In severe cases, lymphoid follicles may develop. CD8+ is the predominant lymphocyte. The epithelial layer can become ulcerated and squamous epithelium replaces the columnar cells. The inflammation is followed by scarring and thickening of the walls, which narrows the small airways.

The elasticity is affected by the replacement of club cells by goblet cells. Club cells enhance the elasticity of the lungs.

The small airways are affected, initially without any breathing problems. The initial inflammation of the small airways is reversible and accounts for the improvement in airway function if smoking is stopped early. In later stages, the inflammation continues.

Further progression leads to progressive squamous cell metaplasia and fibrosis of the bronchial walls. This develops the airflow limitation.

Clinical Manifestations

lottexvleeuwen — 2020-09-21 13:24:30 UTC

Symptoms

Characteristic symptoms are:

Productive cough with white or clear sputum
Wheeze
Breathlessness
Smoker's cough
Colds 'settle on the chest'
Infective exacerbations with purulent sputum

Symptoms can be worsened by cold/damp weather and atmospheric pollution. Systemic effects include hypertension, osteoporosis, depression, weight loss, and reduced muscle mass. People with COPD often struggle with exercise.

Signs

Mild COPD -> no signs or quiet wheezes throughout the chest.

Severe COPD -> patient is tachypnoeic, with prolonged expiration. Accessory muscles of respiration are used and there may be intercostal indrawing on inspiration and pursing of the lips on expiration. Chest expansion is poor, the lungs are hyperinflated and there is loss of normal cardiac and liver dullness.

Patients that remain responsive to CO2 are breathless and rarely cyanosed. Heart failure and oedema are terminal events.

Patients that become insensitive to CO2 often develop oedema and cyanosis, but are not breathless.

Patients with hypercapnia (overload of CO2) can have peripheral vasodilation, bounding pulse, and a coarse flapping tremor of outstretched hands if the PaCO2 is above 10kPa.

Severe hypercapnia causes confusion and progressive drowsiness.

Respiratory failure

Later stages of COPD are characterized by development of respiratory failure. This is defined as:

PaO2 < 8 kPa (60mHg)
Or; PaCO2 > 7 kPa (53 mmHg)

Chronic alveolar hypoxia and hypercapnia lead to constriction of the pulmonary arterioles and pulmonary hypertension. Salt and fluid retention occurs as a result of renal hypoxia.

Pulmonary hypertension

Pulmonary hypertension is defined as symptoms and signs of fluid overload secondary to lung disease.

Diagnosis

lottexvleeuwen — 2020-09-21 13:24:48 UTC

Lung function tests:
- compared to the GOLD criteria. the FEV1/FVC is decreased, as is the FEV1. The peak flow is lower than normal. The decreased lung function is only partially reversible, which is different from asthma.
The CO gas transfer is less effective due to the emphysema.

Scans:
- CT scans are to investigate patterns of emphysema.
There are three types of emphysema:
Centrilobular -> emphysema is in the upper part of the lobe.
panlobular -> emphysema is over the whole lung.
irregular -> emphysema occurs in patches.
- Chest x-ray. More than often the scan looks normal, but hyperinflated lungs (barrel chest) can be indicated and bullae can be identified.
- Blood measures: haemoglobin and hematocrit are important to check the saturation values (pink puffers vs blue bloater). PH is lower due to acidosis in patients with COPD.
- Diffusion function: checks the Va/Q match or mismatch.

One can hear the mucus in the lungs when listening to the lungs of a patient with chronic bronchitis.

Treatment

lottexvleeuwen — 2020-09-21 13:24:55 UTC

The main goal of treatment is to relieve symptoms and reduce further damage to the lungs.

Different treatments:
- Stopping smoking
- Bronchodilators/corticosteroids/muscarinic antagonist
- antibiotics: for acute periods of COPD. It reduces further damage to the lungs.
- Lung transplant: this is the last resort.
Lung reducing surgery: used to get rid of bullae.
- Oxygen therapy: one needs to be cautious with administration of O2. This is due to the blue bloaters that are driven by hypoxemia.

The most used drug therapy is
the combination of muscarinic and b2-agonists.

Prognosis

lottexvleeuwen — 2020-09-21 13:25:03 UTC

It is a chronic and irreversible disease; damage that is done, is done. It is only reversible in the early stages when there is initial inflammation of the smaller airways, if smoking is stopped. One can only manage the symptoms and reduce further damage. The death toll of COPD is increasing, since developing countries are starting to smoke more.

Pathogenesis and pathophysiology: Emphysema

lottexvleeuwen — 2020-09-21 13:25:38 UTC

Emphysema is the abnormal, permanent enlargement of air spaces distal to the terminal bronchiole, accompanied by destruction of alveolar walls. Emphysema is thought to be a secondary result of small airway inflammation and destruction.

It is caused through interrelated events. The trigger is cigarette smoke, but one needs to have a genetic susceptibility to develop emphysema.
The cigarette smoke will induce an immune response, in which macrophages and neutrophils are released.
The macrophages and neutrophils release proteases, which will degrade the extracellular matrix and damage the walls of the airways. Scar tissue will form in the airways and elastase is degraded, which will reduce elasticity. The damaged cells are unable to repair, which causes emphysema to be irreversible.

'blue bloaters' fail to maintain their respiratory effort, which increases their PaCO2 levels. This leads to a stimulation of respiration in the short term, but in the long term these patients become insensitive to CO2 and depend on hypoxemia to drive ventilation. These patients start to retain fluid due to renal hypoxia and increase their erythrocyte production. The result is that the patients are bloated, plethoric, and cyanosed.

CO2 excretion is less affected by Va/Q (match between ventilation and perfusion) mismatch. 'pink puffers' have low to normal PaCO2 values due to increasing alveolar ventilation in an attempt to correct their hypoxia.

Inflammatory response COPD

lottexvleeuwen — 2020-09-21 13:31:58 UTC

COPD Assesment Test

lottexvleeuwen — 2020-09-21 13:32:24 UTC

Dyspnoea scale

lottexvleeuwen — 2020-09-21 13:32:46 UTC

Recommended source (lecturer)

2020-09-22 06:35:09 UTC

Review article COPD

2020-09-22 09:11:12 UTC

Review article COPD

2020-09-22 09:11:49 UTC

Asthma vs COPD

2020-09-22 09:12:48 UTC

Pathogenesis of Emphysema

2020-09-22 09:12:59 UTC

Patterns of Emphysema

2020-09-22 09:13:07 UTC

Elastase/anti-elastase in emphysema

2020-09-22 09:13:16 UTC

Overview of the Pink Puffers and Blue Bloaters

2020-09-22 10:30:00 UTC

Pathogenesis: COPD in general

lottexvleeuwen — 2020-09-22 10:40:46 UTC

Cigarette smoking

Smokers show increased numbers of neutrophil granulocytes. These can release elastases and proteases, which help produce emphysema. An imbalance between protease and antiprotease (a1-antitrypsin) causes damage, with the antiprotease being inhibited by cigarette smoke.

Mucous gland hypertrophy in the larger airways is a response to persistent irritation resulting from inhalation of cigarette smoke.

Infections

Patients with COPD cope badly with respiratory infections, which are often the precipitating cause of acute exacerbations of the disease.

A1-antitrypsin deficiency

A1-antitrypsin is a proteinase inhibitor that is produced in the liver, secreted into the blood, and diffused into the lung. It inhibits proteolytic enzymes that are capable of destroying alveolar wall connective tissue (e.g. neutrophil elastase). In a deficiency, the protein accumulates in the liver, leading to low levels in the lung.

There are three types/alleles of a1-antitrypsin (normal, heterozygous, and homozygous). Homozygous deficiency will not necessarily lead to COPD, but you are more predisposed.

Categorization of COPD according to spirometry

2020-09-22 10:42:30 UTC