Surfactant and Alveolar Proteinosis

 Surfactant and Alveolar Proteinosis

PKGhatak,MD

A Phopholipoprotein compound present in the lung alveoli (air sacs) acts as a Surface Tension Lowering Agent. Alveoli are tiny air sacs, lined by just one layer of pneumocyte type1 cell - inside the sac outside air enters and leaves and outside the alveoli the blood circulates and the exchange of gases takes place. If the surfactant is removed, the wall of the alveoli will come in apposition and will not be separated by the force generated during breathing in the air (inspiration).

If you take two glass sides and put a drop of water on one slide then place the other slide over it; then try to separate those glass slides by pulling them apart, no matter how strong your hands are, you will not able to separate the slides. Now repeat the same experiment with one drop of soap water. The slides will come apart easily. Soap is a surface tension lowering agent. That is the reason the doctors are asking you to wash your hands with soap water as soon as possible in order to minimize covid infection if you were out.

A surfactant molecule has two ends, one end is a Hydrophobic end the other is a Hydrophilic end. The hydrophobic end is turned toward the air, and the other end towards the blood. Thereby keeping air and blood separate.

The Alveolar type 2 cells secrete surfactant. The surfactant molecules inside the cells are called laminar bodies and the extracellular surfactant is chemically the same. Chemically the surfactant is Dipalmitoylphosphatidylcholine. Surfactant is also present in the intestine and inner ear.

There is a balance between surfactant production and removal from the alveoli. Alveolar type 2 cells play a major role in both the formation and removal of the surfactant. In addition, several other factors are also involved in the removal of the surfactant from the lung. The alveolar macrophages, airway epithelial cells and ciliary escalator effect and reabsorption in blood in airways, breakdown of surfactant to its constituents by enzymes- lipid and protein components are all thought to be involved in this process. Granulocyte-Macrophage  stimulating factor plays a crucial role by increasing the production of Macrophages which engulf surfactants.

Group B streptococcus can degrade surfactants, pulmonary infections, pulmonary edema fluid and serum protein also destroy surfactants.

Chromosome 10 carries two genes that code the four proteins that are parts of the surfactant molecule. The deficiency of these genes is inherited as autosomal dominant and also as recessive modes. Congenital absence of surfactant is not compatible with life. In the fetal lung, surfactants are present in small amounts. Maturation of Alveolar type 2 cells correlated with the capacity to generate an adequate amount of surfactant. This becomes a crucial point in the survival of preterm infants with Acute Respiratory Syndrome.

Alveolar Proteinosis:

 

 Alveolar proteinosis:

When the balance between production and removal of surfactant is disrupted and removal grossly lags behind the accumulated surfactant in the alveoli completely fills up the alveolar space; the exchange of gases is markedly impaired and hypoxemia develops. The patients become short of breath, complain of tightness of the chest, and develop fever and marked hypoxemia.

Pulmonary alveolar proteinosis is a rare disease. The incidence is 1:000,000 population, higher in males and high in the age group 30 to 60 years.

The causes of alveolar proteinosis are three. Congenital, Autoimmune and Secondary.

Congenital alveolar proteinosis.

The granulocyte-macrophage colony stimulating factor (GM-CSF) deficiency impairs the clearing of surfactant from alveoli. The disease is inherited as an Autosomal recessive mode. The GM-MSF gene is located in the 5q 3.1 location on chromosome 5.

Autoimmune alveolar proteinosis.

Autoimmune proteinosis accounts for 90 % of all cases. Antibodies to GM-CSF are demonstrated in some cases but not all instances. The response to the removal of antibodies by plasmapheresis and IV therapy; and also Rituximab, a monoclonal antibody to phospholipids and also decreases the lymphocyte B 20 activities, results in the improved outcome, support this theory.

Secondary alveolar proteinosis.

The clinical picture develops the following conditions - cancers like Chronic Myeloid Leukemia, post exposure to inhaled toxic gases, exposure to a toxic level of Nickle.

Laboratory findings and diagnosis.

Hypoxemia is generally severe - often below 87%, with a low PaO2 when on oxygen at 100 %. Clubbing of fingers is present; evidence of weight loss is common. Chest X-ray shows lower and middle lobe dense consolidation, more centrally located giving an appearance of "Bat Wings". Bronchoscopy shows frothy, profuse secretion filling the airways and lung parenchyma. Fluid obtained from bronchoalveolar lavage fluid shows Periodic Acid Schiff (PAS) positive proteinous materials is diagnostic.

Treatment. Maintaining a near normal PaO2 by any means is essential including intubation and mechanical ventilation.

GM -CSF delivered by inhalation is most commonly employed, it may also be given IV. Plasmapheresis can also be undertaken. Bronchoalveolar lavage was a standard mode of treatment until GM-CSF therapy became available.

In resistant cases, Lung Transplantation is the only option that remains.

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