HEREDITARY SPHEROCYTOSIS - PATHOLOGY

Dr.G Bhanu Prakash Animated Medical Videos

27 May 201411:02

Summary

TLDRThe video script delves into the hereditary spherocytosis disorder, discussing its pathology, including the mutation in the spectrin protein causing red blood cell deformities. It highlights the clinical findings such as jaundice, splenomegaly, and the formation of gallstones. The script emphasizes the importance of understanding the structural defects in red blood cells due to spectrin mutations, which lead to reduced life span and the development of anemia and reticulocytosis. It also touches on the treatment options, particularly the benefits of splenectomy for patients with hereditary spherocytosis.

Takeaways

🧬 Hereditary spherocytosis is an autosomal dominant disorder characterized by a reduced life span of red blood cells.
🩸 The normal life span of red blood cells is 120 days, but in hereditary spherocytosis, it is reduced to 10 to 20 days.
🔬 The condition involves mutations in the spectrin protein, which is part of the red blood cell membrane and contributes to its stability.
🔑 The most common mutation is seen in the protein 4.2, which is crucial for maintaining the integrity of the red blood cell membrane.
📚 Spectrin has alpha and beta subunits that attach to the cell membrane at different sites, and mutations can affect these attachment sites.
🔍 The diagnosis of hereditary spherocytosis often involves identifying the structural defect in the red blood cell membrane due to mutations in spectrin.
🌡 The condition can lead to extravascular hemolysis, where red blood cells are destroyed outside the blood vessels, causing anemia.
💉 Splenectomy is a common treatment for hereditary spherocytosis, as it can help reduce the destruction of red blood cells.
🩹 After splenectomy, the anemia is corrected, but the spherocytes, which are abnormally shaped red blood cells, will remain in the blood.
🧫 The osmotic fragility test is a key diagnostic tool, where red blood cells from patients with hereditary spherocytosis are more prone to rupture.
🛡 Vaccination against encapsulated organisms such as pneumococcus, Haemophilus influenzae, and meningococcus is important after splenectomy to prevent infections.

Q & A

What is Hereditary Spherocytosis?
-Hereditary Spherocytosis is an autosomal dominant disorder characterized by the presence of abnormally shaped red blood cells, or spherocytes, which can lead to hemolysis and anemia.
What is the normal life span of red blood cells in Hereditary Spherocytosis?
-In Hereditary Spherocytosis, the life span of red blood cells is significantly reduced, typically to 10 to 20 days, compared to the normal life span of 120 days.
What is the role of Spectrin in red blood cells?
-Spectrin is a protein that forms a part of the red blood cell membrane skeleton. It helps maintain the cell's shape and flexibility, and mutations in the Spectrin gene can lead to Hereditary Spherocytosis.
How do mutations in the Ankyrin protein affect Hereditary Spherocytosis?
-Ankyrin mutations can result in the disruption of the binding of Spectrin to the red blood cell membrane, leading to a loss of membrane stability and the formation of spherocytes.
What is the clinical significance of Band 3 in the red blood cell membrane?
-Band 3 is a crucial protein that facilitates the transport of anions across the red blood cell membrane. Mutations in Band 3 can contribute to the development of Hereditary Spherocytosis.
What are the clinical findings associated with Hereditary Spherocytosis?
-Clinical findings in Hereditary Spherocytosis include jaundice, splenomegaly, and the formation of gallstones, which are due to the increased breakdown of red blood cells and bilirubin production.
Why is splenomegaly common in Hereditary Spherocytosis?
-Splenomegaly occurs because the spleen filters out the abnormal spherocytes from the bloodstream, leading to an enlarged spleen as it works to remove these cells.
What is the typical treatment for Hereditary Spherocytosis?
-The most common treatment for Hereditary Spherocytosis is splenectomy, which is the surgical removal of the spleen to reduce the destruction of red blood cells.
What are the consequences of not treating Hereditary Spherocytosis?
-If left untreated, Hereditary Spherocytosis can lead to chronic anemia, fatigue, and complications such as gallstones and an increased risk of infections due to a weakened immune system.
How does the loss of potassium and water affect the red blood cells in Hereditary Spherocytosis?
-The loss of potassium and water can cause the red blood cells to become more rigid and less able to deform, which is crucial for their passage through the spleen and other narrow vessels.
What is the role of the sodium-potassium pump in red blood cells?
-The sodium-potassium pump is essential for maintaining the proper balance of ions inside and outside the red blood cells, which is critical for their function and shape.

Outlines

00:00

🧬 Hereditary Spherocytosis: Pathology and Clinical Features

The first paragraph discusses hereditary spherocytosis, an autosomal dominant disorder characterized by a reduction in life span of red blood cells (RBCs). It explains the normal structure of the RBC membrane and how mutations in the spectrin protein lead to the disorder. The summary highlights the role of protein 4.2 and actin in maintaining the integrity of the RBC, and how mutations affect the cell's shape and lead to hemolysis. The most common mutation site is in the ankyrin protein, which is crucial for linking spectrin to the membrane. The paragraph also touches on the clinical implications of these mutations, such as increased osmotic fragility and the reduced life span of RBCs, which is typically 10 to 20 days in hereditary spherocytosis compared to the normal 120 days.

05:01

🏥 Clinical Manifestations of Hereditary Spherocytosis

The second paragraph delves into the clinical findings associated with hereditary spherocytosis, which include the development of splenomegaly, hepatomegaly, and gallstones due to the trapping of abnormal RBCs in the spleen. It emphasizes the importance of recognizing the structural defect in the RBC membrane caused by mutations in the ankyrin protein. The summary explains how the spleen's role in filtering out the misshapen RBCs leads to anemia and the formation of spherocytes. It also discusses the complications that can arise from the disease, such as extravascular hemolysis, which can lead to reticulocytosis and an increased rate of bilirubin production, as well as the potential for jaundice and gallstone formation.

10:03

🛑 Treatment and Management of Hereditary Spherocytosis

The third paragraph outlines the treatment options for hereditary spherocytosis, with splenectomy being the most beneficial procedure for patients. It discusses how the removal of the spleen can correct anemia but notes that spherocytes will persist in the blood. The summary also mentions the importance of vaccination against encapsulated organisms such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae, as the spleen's function in filtering these organisms is compromised post-splenectomy. The paragraph concludes by reiterating the key points about the disease's pathogenesis and the importance of recognizing the characteristic features of hereditary spherocytosis for proper diagnosis and treatment.

Mindmap

Keywords

💡Hereditary Spherocytosis

Hereditary Spherocytosis is an autosomal dominant disorder characterized by the production of abnormally shaped red blood cells, or spherocytes, which are less flexible and prone to hemolysis. In the video, it is the main theme, explaining its pathology and genetic aspects. The script mentions that most mutations are seen in the protein 4.2 and spectrin, which are essential for the stability of the red blood cell membrane.

💡Spherocytes

Spherocytes are red blood cells that have lost their typical biconcave shape and become spherical due to a defect in the cell membrane. They are more susceptible to destruction in the spleen, which is a key aspect of the hemolytic process in Hereditary Spherocytosis discussed in the video. The script describes how these cells are present in the patient's blood and contribute to the condition's clinical manifestations.

💡Hemolysis

Hemolysis refers to the destruction of red blood cells and the release of hemoglobin into the bloodstream. It is a central feature of Hereditary Spherocytosis, as the script explains that the abnormal membrane of spherocytes leads to their premature breakdown. This process results in anemia and other clinical findings associated with the condition.

💡Anemia

Anemia is a condition characterized by a deficiency in the number of red blood cells or the amount of hemoglobin in the blood. In the context of the video, anemia is a consequence of the hemolysis seen in Hereditary Spherocytosis, where the destruction of red blood cells outpaces the body's ability to produce new ones, as illustrated by the reduced life span of red blood cells in affected individuals.

💡Spectrin

Spectrin is a protein that plays a crucial role in maintaining the structural integrity of the red blood cell membrane. The script discusses how mutations in the spectrin gene can lead to Hereditary Spherocytosis by causing instability in the cell membrane, which in turn leads to the formation of spherocytes and subsequent hemolysis.

💡Protein 4.2

Protein 4.2 is a component of the red blood cell membrane that interacts with other proteins like spectrin to maintain the cell's shape and flexibility. The video script highlights that mutations in the gene encoding protein 4.2 can result in Hereditary Spherocytosis by affecting the structural stability of the red blood cell membrane.

💡Autoimmune Hemolytic Anemia

Autoimmune Hemolytic Anemia is a condition where the immune system mistakenly attacks and destroys red blood cells. The script mentions this as a differential diagnosis to consider when evaluating patients with anemia and hemolysis, which are also features of Hereditary Spherocytosis.

💡Splenic Sequestration

Splenic Sequestration is a phenomenon where the spleen traps a large volume of blood, leading to a rapid drop in blood pressure and potentially life-threatening anemia. The video script discusses how the spleen plays a role in the hemolysis of spherocytes in Hereditary Spherocytosis, although it does not explicitly mention sequestration, the concept is related to the spleen's role in the condition.

💡Osmotic Fragility

Osmotic Fragility is a laboratory test that measures the susceptibility of red blood cells to rupture when exposed to a hypotonic solution. The script refers to this test as a means to identify the increased fragility of spherocytes in Hereditary Spherocytosis, which is a key diagnostic feature of the condition.

💡Splenectomy

Splenectomy is the surgical removal of the spleen. In the context of the video, it is mentioned as a treatment option for Hereditary Spherocytosis, as removing the spleen can reduce the rate of red blood cell destruction, thereby alleviating the symptoms of hemolysis and anemia.

💡Glycolysis

Glycolysis is the metabolic pathway that converts glucose into pyruvate, generating energy in the form of ATP. The script touches on the importance of glycolysis in red blood cells, which lack mitochondria and rely on glycolysis for their energy needs. In Hereditary Spherocytosis, impaired glycolysis can contribute to the reduced life span of red blood cells.

Highlights

Hereditary Spherocytosis is an autosomal dominant disorder affecting red blood cells.

The condition is characterized by a reduced life span of red blood cells due to membrane defects.

Spectrum of the disorder includes protein 4.2 and 4.1, integral to the red blood cell membrane.

Mutations in the protein 4.2 and 4.1 can result in hereditary spherocytosis.

Clinical findings often include jaundice, splenomegaly, and the formation of gallstones.

The most common mutation site in hereditary spherocytosis is in the protein 4.2.

The normal life span of red blood cells is reduced to 10 to 20 days in hereditary spherocytosis.

Osmotic fragility test is a key diagnostic tool for hereditary spherocytosis.

Splenectomy is a beneficial treatment for patients with hereditary spherocytosis.

After splenectomy, anemia is corrected, but spherocytes will remain in the blood.

Vaccination against encapsulated organisms is important post-splenectomy.

The most characteristic feature of hereditary spherocytosis is an increase in mean corpuscular hemoglobin concentration (MCHC).

The pink test is indicative of the osmotic fragility of red blood cells in hereditary spherocytosis.

Glycolysis cannot occur properly in the red blood cells due to the defect, leading to a lack of ATP.

The sodium-potassium pump failure in red blood cells leads to increased intracellular sodium and water.

Hereditary spherocytosis can cause extravascular hemolysis due to the trapping of spherocytes in the spleen.

The most common clinical findings are due to hemolysis, including anemia and reticulocytosis.

Identification and treatment of hereditary spherocytosis are crucial to prevent complications.