Hematology Lecture Two & Three PDF

Lymphatic system and Hemoglbin Lymphatic system: The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. Lymph is a clear fluid carried by the lymphatic vessels back to the heart fo...

Lymphatic system and Hemoglbin Lymphatic system: The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system and complementary to the circulatory system. Lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. The Latin word for lymph, lympha, refers to the deity of fresh water, "Lympha". 1  Unlike the circulatory system that is a closed system, the lymphatic system is open. The human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma from the blood. Roughly 17 litres of the filtered blood is reabsorbed directly into the blood vessels, while the remaining three litres are left in the interstitial fluid. One of the main functions of the 2  lymphatic system is to collects this excess fluid, now called lymph, from tissues in your body and moves it along until it's ultimately returned to your bloodstream. Parts of the lymphatic systems: It consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphatic tissue and lymph. lymphoid organs divided into: 1. Primary lymphoid organs Bone marrow (Hematopioesis) Thymus (T lymphocyte ) 2. Secondary lymphoid organs Spleen(to produce immune cells to fight antigens , to remove particulate matter and aged blood cells, mainly red blood cells to produce blood cells during fetal life.) Lymph nodes 3  Function : 1. The main function is that of immune defense. ▪ The cells of the lymph are mostly lymphocytes(Associated lymphoid organs are composed of lymphoid tissue, and are the sites either of lymphocyte production or of lymphocyte activation. ) ▪ These include the lymph nodes (where the highest lymphocyte concentration is found), the spleen, the thymus, and the tonsils. Lymphocytes are initially generated in the bone marrow. The lymphoid organs also contain other types of cells such as stromal cells for support. ▪ Lymphoid tissue is also associated with mucosas such as mucosa- associated lymphoid tissue (MALT). 2. It is responsible for the removal of interstitial fluid from tissues. 4  3. It absorbs and transports fatty acids and fats as chyle from the digestive system. 4. It transports white blood cells to and from the lymph nodes into the bones. 5. The lymph transports antigen-presenting cells, such as dendritic cells, to the lymph nodes where an immune response is stimulated. Causes of swollen lymph nodes: Infections: Strep throat , Measles ,Ear infections Infected (abscessed) tooth Mononucleosis ,Skin or wound infections, such as cellulitis ,Human immunodeficiency virus (HIV) ,Tuberculosis,- syphilis ,Toxoplasmosis Autoimmune diseases: Lupus ,- Rheumatoid arthritis. Cancers: 1. Lymphoma ,Leukemia 2. Other cancers (metastasized ).Cancer to lymph node. Where does hematopoiesis occur? INTRAmedullarry: 5 Hematopoiesis that occurs in your bone marrow is called medullary hematopoiesis. Blood cells get made in your bone marrow and released into your bloodstream. EXTRAmedullary: Less often, hematopoiesis takes place in other parts of your body, like your liver and spleen. Hematopoiesis that occurs outside of your bone marrow is called extramedullary. How to examine bone marrow? 1. Cellularity Cellularity is a hematopoietic cell/fat cell ratio. Normal cellularity = 1 Cellularity > 1 refer as “Marrow Hyperplasia” Cellularity < 1 refer as “Marrow Hypoplasia” The mostly evaluated from biopsy specimen%) 2. Differential cell count Granulocytic series (65%) (M) Erythrocytic series (20%) (E) Lymphocyte (10%) Others (5%) 3. Myeloid:Erythroid ratio (M:E ratio) = 2:1,4:1 (300 to 500 cells are scanned) 4. Iron accumulation Storage iron is “hemosiderin”. 6  It contained by nucleated erythroid cell. is the mostly stain for Prussian blue marrow iron storage. iron stores is benefit for evaluation of anemia. RBCs morphology 7 The mature erythrocyte has a biconcave, discoid shape and is anucleated. This design allows for the flexibility needed to navigate the cardiovascular system and for an increased surface area which supports sufficient gas exchange and permits the cell to carry out its function. A phospholipid bilayer membrane frames the structure of this unique cell and is maintained by a network of proteins that make up the cytoskeleton. This cytoskeleton is composed of spectrin, actin, band 3, protein 4.1, and ankyrin—which allows for cellular structural integrity as well as malleability. 8 RBCs life cycle 9 Haemoglobin synthesis: Hemoglobin is an oxygen-binding protein found in erythrocytes that transports oxygen from the lungs to tissues. Each hemoglobin 10  molecule is a tetramer made of four polypeptide globin chains. Each globin subunit contains a heme moiety formed of an organic protoporphyrin ring and a central iron ion in the ferrous state (Fe2+). The iron molecule in each heme moiety can bind and unbind oxygen, allowing for oxygen transport in the body. The most common type of hemoglobin in the adult is HbA, which comprises two alpha-globin and two beta-globin subunits. Different globin genes encode each type of globin subunit. The two main components of hemoglobin synthesis are globin production and heme synthesis. Globin chain production occurs in the cytosol of erythrocyte precursors and occurs by genetic transcription and translation. Many studies have shown that the presence of heme induces globin gene transcription. Genes for the alpha chain are on chromosome 16, and genes for the beta chain are on chromosome 11. Heme synthesis occurs in both the cytosol and the mitochondria of erythrocytes precursors. It begins with glycine and succinyl coenzyme A and ends with the production of a protoporphyrin IX ring. The binding of the protoporphyrin to a Fe2+ ion forms the final heme molecule. There are a few different forms of normal hemoglobin in human blood. The percent prevalence of each hemoglobin type depends on the stage of development. HB types: ❖ During pregnancy, the fetus primarily produces fetal hemoglobin (HbF). HbF comprises two a and two gamma-globin subunits. HbF has a stronger oxygen affinity than HbA, allowing oxygen to flow from maternal to fetal circulation through the placenta. Production of HbF drops significantly after birth, reaches low, 11  near-adult levels by two years, and ultimately makes up 2 to 3% of hemoglobin in adults. HbA, the most common adult form of haemoglobin, comprises two alpha and two beta-globin subunits. Inversely to HbF, HbA production explodes after birth and ultimately makes up 95-98% of hemoglobin in adults. HbA2 is a less common adult form of hemoglobin. It comprises two alpha and two delta-globin subunits and makes up 1 to 3% of hemoglobin in adults. Briefly : There are several different types of hemoglobin, the two most common of which are: Hemoglobin A (HgbA): This is the most common type found in healthy adults. Hemoglobin F (HgbF): Also known as fetal hemoglobin, this type is found in fetuses and newborn. It is replaced by HgbA shortly after birth. There are abnormal types of hemoglobin that affect both the shape of RBCs but also their ability to transport oxygen and carbon dioxide, including: Hemoglobin S (HgbS): This type of hemoglobin is found in sickle cell disease that causes RBCs to become stiff and crescent- shaped. Hemoglobin C (HgbC): This type of hemoglobin does not carry oxygen well and is associated with mild anemia. Hemoglobin E (HgbE): This type of hemoglobin is mostly found in people of Southeast Asian descent that may cause mild anemia or no symptoms at all. 12  13  Thalassaemia Thalassemias are inherited blood disorders that result in abnormal hemoglobin. Cause : Both α- and β-thalassemias are often inherited in an autosomal recessive manner. For the autosomal recessive forms of the disease, both parents must be carriers for a child to be affected. If both parents carry a hemoglobinopathy trait, the risk is 25% for each pregnancy for an affected child. The genes involved in thalassemia control the production of healthy hemoglobin. Hemoglobin binds oxygen in the lungs and releases it when the red cells reach peripheral tissues, such as the liver. The binding and release of oxygen by hemoglobin are essential for survival. 14 Thalassemia Types: The two main types of thalassemia are alpha and beta, based on which part of the hemoglobin protein isn't being made. 1. Alpha-Thalassemia Alpha-thalassemia is related to changes or deletions in genes that make a protein subunit of hemoglobin called alpha-globin. This involves two adjacent genes (HBA1 and HBA2) on one chromosome.1 You inherit two of these genes from each parent since you get one chromosome from each parent (a total of four genes). This can result in these types of thalassemia: Alpha-thalassemia minor (trait): Involves two gene deletions and causes mild or no symptoms Alpha-thalassemia intermedia (deletional HbH disease): Involves three gene deletions and mild to moderate symptoms Non-deletional HbH disease (constant spring): Involves reduced alpha-globin activity and severe symptoms Alpha-thalassemia major (Hb Bart’s hydrops fetalis): Involves four gene deletions and severe symptoms that can be fatal during gestation or shortly after birth While usually an inherited condition, alpha-thalassemia can also develop secondary to a cancer of the blood-forming cells. In most cases, this occurs in a person with myelodysplastic syndrome. 15  2. Beta-Thalassemia Beta-thalassemia involves changes (mutations) of the HBB gene that makes a protein subunit of hemoglobin called beta-globin.3 You inherit one of these genes from each parent. This can result in these types: Beta-thalassemia minor (trait): Involves one faulty gene and causes mild symptoms or none at all Beta-thalassemia intermedia: Involves two faulty genes and causes mild to moderate symptoms Beta-thalassemia major (Cooley's anemia): Involves two faulty genes and causes severe symptoms Dominant beta-thalassemia: A very rare type that involves one faulty gene and causes mild to moderate symptoms Beta thalassemia can extremely rarely occur as an acquired, non- inherited condition, usually in a person with myelodysplastic syndrome. Thalassemia Causes and Risk Factors: Thalassemia happens when you inherit certain gene mutations or gene deletions. Alpha-thalassemia usually involves mutations in the HBA1 and HBA2 genes, but there are rare syndromes involving other genes.Beta-thalassemia is usually the result of a mutation in the HBB gene. Except in rare instances, if you inherit these gene mutations from only one parent, you'll be a silent carrier and won't develop thalassemia. When both parents are carriers, the children have a 25% chance of inheriting two trait genes and developing the disease. They have a 16 50% chance of being a trait carrier. Thalassemia is most common in people whose ancestry is: Italian Greek Middle Eastern Southern Asian African Acquired alpha-thalassemia or beta-thalassemia are rare and usually seen when a person has a type of blood cancer. The cancerous cells have undergone non-inherited genetic changes that result in thalassemia. Thalassemia Symptoms Symptoms vary according to type and severity. Anemia causes most signs and symptoms associated with thalassemia, including:67 Tiredness Weakness Shortness of breath Fast heartbeat Pale skin Dizziness, fainting Headaches Trouble concentrating Leg cramps 17 Children with severe types of thalassemia may have: Pale skin Jaundice (yellowing of the skin and whites of the eyes) Enlarged spleen or liver Dark urine Loss of appetite Intellectual or developmental disabilities Changes to facial bones Most people with thalassemia have health problems within a few months of birth. In mild cases, symptoms may not be apparent until later in childhood or adulthood. How Thalassemia Is Diagnosed If your provider suspects thalassemia, they'll likely ask about your family's medical history. Diagnostic testing may include: Complete blood count (CBC): To measure different components of blood and blood cells Hemoglobin electrophoresis: To detect different types of hemoglobin Ferritin test: To measure iron in the blood Molecular genetic testing: To detect gene mutations and confirm the diagnosis Newborn screening tests check for many blood abnormalities, including beta-thalassemia. 18 If you're pregnant and think your fetus may be at risk of thalassemia, ask your healthcare provider about prenatal testing such as: Chorionic villus sampling (CVS): Involves taking a sample of tissue from the placenta at 10 to 13 weeks gestation Amniocentesis: Involves taking an amniotic fluid sample at 15 to 20 weeks gestation9 Ultrasound: A noninvasive procedure that helps providers see how blood flows through cerebral arteries, usually at 13 to 14 weeks gestation. 19  20