patophysiology of blood and bone marrow disorders

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  • Patophysiology of blood and bone marrow disorders

  • Pathophysiology of bloodPatophysiology of RBCBasic informationHemoglobinLaboratory tests IronErythropoetin a erythropoesisAnemias

    Principles of light microscopyObservation of blood smearsTheoretical partPractical part

  • Definition of hematology conceptionHematology (gr. haima-haimatos blood, gr. logos science- hematology, science about blood a blood disorders) is deal with blood and haemoplastic bodiesPeripheral bloodRed bone marrowLymph - nodesLiver, spleen

  • Basic anatomical and physiological notesBasic haemoplastic bodies:

    Bone marrow Thymus

    Lymph-nodes MALT (mucosa associated lymphoid tissue) Spleen Peripheral blood

    Central haemoplastic and immune bodiesPeripheralhaemoplastic and immune bodies

  • Physiological function of blood

  • Ontogenesis of haemopoiesisYolk sackLiver: 6. week - birthSpleen, thymus, nodes: 8.- 16. weekRed bone marrow: 12. week

    Extramedullar haemopoiesis

  • Bone marrowPlace of haemopoiesisRed bone marrowhaemopoeticYellow bone marrowAdiposal tissue

  • Red bone marrowstromasystem of reticular cellssystem of reticular fibrescollagen fibersfibronectin, laminin, hemonectinhematogenous filamentssinusoidal capillaries

  • Haemopoiesis

  • Factors necessary for haemopoiesisPluripotent stem cellis able either mitotic or meiotic cell divisionMicroenvironment e.g. bone marrowpart of b.m are cells and ECM Growth factorsso-called colony stimulating factors = CSF (are secreted glycoproteins which bind to receptor proteins on the surfaces of hemopoietic stem cells and thereby activate intracellular signaling pathways which can cause the cells to proliferate and differentiate into a specific kind of blood cell) erythropoietin

  • SPECIFIC IMMUNE DEFENSEGAS TRANSPORTHEMOSTASISIMMUNE RESPONSE

  • Erythropoesis

  • Structure of RBCThe mature red blood cell is easily recognized because of its unique morphology. At rest, the red blood cell takes the shape of a biconcave disc with a mean diameter of 8 m, a thickness of 2 m, and a volume of 90 fL. It lacks a nucleus or mitochondria, and 33% of its contents is made up of a single protein, hemoglobin. Intracellular energy requirements are largely supplied by glucose metabolism, which is targeted at maintaining hemoglobin in a soluble, reduced state, providing appropriate amounts of 2,3-diphosphoglycerate (2,3-DPG), and generating adenosine triphosphate (ATP) to support membrane function. Lifespan of RBC???

  • A: Adult red blood cells are characterized by their lack of a nucleus, and biconcave disc shape. Red blood cells are extremely pliable as they pass through small vessels and sinusoids.

    B: The section of a small blood vessel demonstrates the ability of red blood cells to undergo major shape distortions. Red blood cell morphology

  • Red Cell Production Committed bone marrow cells proliferate and differentiate through the erythroblast and normoblast stages to reticulocytes, which are released into the bloodstream and finally become erythrocytes.

  • Mature of RBCerythropoetin, Fe, folate, vit. B12proerythroblast lace chromatinbasophilic erythroblast strong basophilic cytoplasmadue to synthesis of Hbpolychromatophilic erythroblastorthochromatic erythroblast no dividingreticulocyte expulsion of nucleusrest of polyribosomesthe period from stem cell to emergence of the reticulocyte in the circulation normally takes approximately 1 week maturation of reticulocyte to erythrocyte takes approximately 24 to 48 hours

  • Reticulocytes

  • Count of RBC Normal values: female: 3,8 5,2 x 1012 / 1 litr male: 4,2 5,8 x 1012 / 1 litr

    Decrease: anemia, expansion of ECF

    Increase: polycytemia, dehydratation

  • Destruction of red blood cellsThe destruction of red blood cells is mediated by a group of large phagocytic cells found in the spleen, liver, bone marrow, and lymph nodes.

    During red blood cell destruction, amino acids from the globin chains and iron from the heme units are salvaged and reused, whereas the bulk of the heme unit is converted to bilirubin, the pigment of bile.

  • Bilirubin, which is insoluble in plasma, attaches to plasma proteins for transport to the liver, where it removed from the blood and conjugated with glucuronide to render it water soluble so that it can be excreted in the bile.

    The plasma-insoluble form of bilirubin is referred to as unconjugated bilirubin the water-soluble form is referred to as conjugated bilirubin.

    Destruction of red blood cells

  • HemoglobinThe red blood cell is, basically, a container for hemoglobin a 64,500 dalton protein made up of 4 polypeptide chains, each containing an active heme group. Each heme group is capable of binding to an oxygen molecule. The respiratory motion of hemoglobin, that is, the uptake and release of oxygen to tissues, involves a specific change in molecular structure

  • Cellular metabolismThe stability of the red blood cell membrane and the solubility of intracellular hemoglobin depend on four glucose-supported metabolic pathways:

    EMBDEN-MEYERHOFF PATHWAY METHEMOGLOBIN REDUCTASE PATHWAY PHOSPHOGLUCONATE PATHWAY LUEBERING-RAPAPORT PATHWAY

  • Red blood cell metabolic pathways The Embden-Meyerhoff pathway is responsible for the generation of high energy phosphate (ATP) for membrane maintenance, whereas the other pathways support hemoglobin function.

    The methemoglobin reductase (NADH-diaphorase) pathway is required to maintain hemoglobin in a reduced state.

    The phosphogluconate pathway helps counteract environmental oxidants.

    The Luebering-Rapaport pathway generates intracellular 2,3-DPG.

  • Iron metabolismBody iron is found in several compartments.

    About 80 % is complexed to heme in hemoglobin, and most of the remaining iron (about 20 %) is stored in the bone marrow, liver, spleen, and other organs.

    Iron in the hemoglobin compartment is recycled.

    When red blood cells age and are destroyed in the spleen, the iron from their hemoglobin is released into the circulation and returned to the bone marrow for incorporation into new red blood cells, or to the liver and other tissues for storage.

  • Dietary iron helps to maintain body stores.

    Iron, principally derived from meat, is absorbed in the small intestine, especially the duodenum. Diagrammatic representation of the iron cycle, including its absorption from the gastrointestinal tract, transport in the circulation, storage in the liver, recycling from aged red cells destroyed in the spleen, and use in the bone marrow synthesis of red blood cells. Iron metabolism

  • When body stores of iron are diminished or erythropoiesis is stimulated, absorption is increased.

    Normally, some iron is sequestered in the intestinal epithelial cells and is lost in the feces as these cells slough off.

    The iron that is absorbed enters the circulation, where it attaches a transport protein called transferrin. From the circulation, iron can be deposited in tissues such as the liver, where it is stored as ferritin , a proteiniron complex, which can easily return to the circulation.

    Serum ferritin levels, which can be measured in the laboratory, provide an index of body iron stores.

    Iron metabolism

  • Overview red blood cellThe function of red blood cells, facilitated by the iron-containing hemoglobin molecule, is to transport oxygen from the lungs to the tissues.The production of red blood cells, which is regulated by erythropoietin, occurs in the bone marrow and requires iron, vitamin B12, and folate.The red blood cell, which has a life span of approximately 120 days, is broken down in the spleen; the degradation products such as iron and amino acids are recycled.The heme molecule, which is released from the red blood cell during the degradation process, is converted to bilirubin and transported to the liver, where it is removed and rendered water soluble for elimination in the bile.

  • Laboratory testsRed blood cells can be studied by means of a sample of blood. In the laboratory, automated blood cell counters rapidly provide accurate measurements of red cell content and cell indices. The (RBC) measures the total number of red blood cells in 1 mm3 of blood.

  • The percentages of reticulocytes (normally approximately 1%) provides an index of the rate of red cell production.

    The hemoglobin (grams per dL of blood) measures the hemoglobin content of the blood. The major components of blood are the red cell mass and plasma volume.

    Laboratory tests

  • The hematocrit measures the percentage of red cell mass in 100 mL of blood . To determine the hematocrit, a sample of blood is placed in a glass tube, which is then centrifuged to separate the cells and the plasma. The hematocrit may be deceptive because it varies with the quantity of extracellular fluid, rising with dehydration and falling with overexpansion of extracellular fluid volume. Laboratory tests

  • Red cell indices are used to differentiate types of anemias by size or color of red cells:The mean corpuscular volume (MCV) reflects the volume or size of the red cells The mean corpuscular hemoglobin concentration (MCHC) is the concentration of hemoglobin in each cell - (anemias are described as normochromic (normal color or MCHC) or hypochromic (decreased color or MCHC). Mean cell hemoglobin (MCH) refers to the mass of the red cell and is less useful in classifying anemia

    Laboratory tests

  • Disorders of red blood cells

  • Pathology of blood and haemoplastic functionsLack of