MBBS: Phospholipids and Respiratory Distress Syndromes

Objectives for MBBS Students

• Students should be able to discuss phospholipids, including classification of glycerophospholipids and sphingophospholipids, synthesis and degradation.
• Students should also be able to discuss surfactant, its biosynthesis and function.
• Topics include the Law of Laplace, Respiratory Distress syndrome (RDS), neonatal respiratory distress syndrome, and adult respiratory distress syndrome.

Case of Neonatal Respiratory Distress Syndrome

• A 30-year-old pregnant woman (G3P2) gave birth to a 1.5 kg baby girl at 30 weeks gestation via Cesarean section.
• The mother received a dose of betamethasone 10 hours before delivery.
• The baby was resuscitated, intubated, and given surfactant within 15 minutes of delivery.
• Apgar scores were 2, 5, and 6 at 1, 5, and 10 minutes, respectively.
• The baby was mechanically ventilated due to severe respiratory distress syndrome (RDS).

Phospholipids

• Phospholipids (or phosphatides) are a type of compound lipid containing a phosphate group.
• Phospholipids are composed of fatty acids (saturated and unsaturated), a nitrogenous base (choline, serine, threonine, or ethanolamine), phosphoric acid, and fatty alcohols (glycerol, inositol, or sphingosine).

Glycerophospholipids

• Type 2 Lecithin (phosphatidylcholine) is the most abundant phospholipid in cell membranes.
• It's crucial for body choline storage (methyl group donor in methylation reactions).
• It's involved in nerve impulse transmission (choline-acetylcholine).
• Lysolecithin removes fatty acids from lecithin.
• Lecithin maintains surface tension and adherence of inner lung surface.
• Deficiency causes Respiratory Distress Syndrome (RDS) in infants.

Common Glycerophospholipids

• Phosphatidic acid: The simplest phospholipid with no specific functions.
• Lecithin (phosphatidylcholine): Abundant in cell membranes, critical for structure and fluidity. In the lungs, dipalmitoylphosphatidylcholine (DPPC) is a key component of pulmonary surfactant, reducing surface tension.

Other Phospholipids

• Phosphatidyl ethanolamine (cephalin): Similar to lecithin but replaces choline with ethanolamine. Important in blood clotting and membrane processes.
• Phosphatidyl serine: Crucial for cell integrity, especially in the brain. Declines with age. Plays a role in cell signaling, including apoptosis (programmed cell death) where it signals phagocytosis.
• Phosphatidyl inositol: A less common component of cell membranes. Involved in cell signaling.

Glycerophospholipid Synthesis

• The liver synthesizes glycerophospholipids.
• Synthesis requires ATP, glycerol kinase, fatty acyl CoA, thiokinase, and CTP.
• It includes the activation of glycerol, fatty acids, choline, or ethanolamine, using ATP and coenzymes, then the assembly of the final phospholipid molecule.

Glycerophospholipid Degradation

• Phospholipases (A1, A2, C, D) are enzymes involved in the breakdown processes of glycerophospholipids.
• They act on different bonds within the phospholipid molecule to release components, such as fatty acids, glycerol, and phosphoryl base.

Sphingophospholipids

• Sphingomyelin is a sphingolipid containing sphingosine, a fatty acid, phosphorylcholine (phosphate + choline), serving as a major component in the brain and nerve tissue.
• Synthesis starts with palmitic acid, and its combination with serine then acyl-CoA, creating ceramide.
• Ceramide then reacts with phosphatidylcholine to form sphingomyelin and diacylglycerol.

Sphingomyelin Degradation

• Sphingomyelinase (an enzyme in lysosomes) breaks down sphingomyelin into ceramide and phosphocholine.
• Ceramidase then degrades ceramide into sphingosine and fatty acids.

Niemann-Pick Disease

• A genetic absence of sphingomyelinase causes Niemann-Pick disease.
• Sphingomyelin builds up in the liver and spleen, enlarging these organs and causing problems.
• It can also cause unsteady gait, speech difficulties, swallowing problems, widespread brain damage (dementia), and seizures.

Lysosomal Storage Disorders

• They are genetic diseases related to the metabolism of sphingolipids or other complex molecules, resulting in their accumulation in lysosomes, causing dysfunction in various organs of the body.
• This accumulation leads to many physical problems.

Pulmonary Surfactant

• A complex mixture of lipids (90%) and proteins (10%).
• Secreted by type II alveolar epithelial cells (pneumocytes).
• Crucial for reducing surface tension in the alveoli to prevent collapse.

Surfactant Composition

• Phospholipids (mostly phosphatidylcholine).
• Neutral lipids.
• Hydrophilic proteins (SP-A, SP-D).
• Hydrophobic proteins (SP-B, SP-C).

Surfactant Function

• Lowers alveolar surface tension.
• Stabilizes alveoli, maintaining their size.
• Prevents alveolar collapse, allowing easier breathing.
• Maintains uniform alveolar size.

Alveolar Stability

• Pulmonary surfactant, and alveolar interdependence are two factors that oppose the tendency of alveoli to collapse, allowing the lungs to operate effectively.

Law of Laplace

• The relationship between pressure in the alveoli, surface tension, and radius of the alveoli.
• Pressure is directly proportional to surface tension and inversely proportional to alveolar radius.
• Implications for RDS in newborns: Smaller alveoli will experience greater pressure differentials.

Respiratory Distress Syndrome in Newborns

• Premature infants may not produce enough surfactant due to underdeveloped lungs, leading to RDS issues.

Treatment for Respiratory Distress Syndrome

• Surfactant replacement therapy is essential for managing RDS in premature infants.

Summary of Questions

• Students have questions about phospholipid classifications, common types, synthesis steps, functions, lysosomal storage disorders, cells involved in surfactant secretion, surfactant components, functions, forces maintaining or collapsing alveoli, and more.

Fill in the Blanks

• This section provides incomplete sentences related to phospholipids, surfactant, respiratory distress conditions, etc. for students to fill in based on previous information about the various topics discussed.

This quiz focuses on key concepts related to phospholipids, including their classification and functions, particularly in the context of surfactant biosynthesis and respiratory distress syndromes. Students will explore clinical cases such as neonatal respiratory distress syndrome and understand the implications of phospholipid functions in health and disease.