Hematology Physio

• Blood

  Fluid of life, fluid of growth, fluid of health
• Components of blood

  Blood is a mixture of cellular components suspended in plasma. It is a type of connective tissue since it is formed in bone marrow
• Cellular components of blood

  • Erythrocytes (RBCs)
  • Leukocytes (WBCs)
  • Thrombocytes (platelets)
• Total Blood Volume: 8% of body weight, 2.75 / 5.5 liters of blood is plasma (remaining is the cellular portion)
• 3 General Characteristics of Blood

  • 38°C (100.4°F) is normal temperature
  • High viscosity (denser than water)
  • Slightly alkaline pH (7.35–7.45)
• Functions of Blood

  • Transports: Nutrients, O2 & CO2, Waste Products, Hormones, Electrolytes
  • Protection and Defense: Foreign organisms, Injury/infection, Clotting process, Body temperature
  • Maintains Homeostasis, Regulation of pH
• Separation of Components

  Plasma = Less Dense Hematocrit "Packed Cells" More Dense
• Plasma

  Is the fluid portion of the blood. It contains proteins, inorganic and organic substances. If left stand, it will clot. Removing the clot will leave serum which is identical to plasma in its constituents except for fibrinogen, clotting factors (prothrombin,factor V and VIII). Also serum has higher quantities of serotonin (vasoconstrictors because of the breakdown of platelets). Is similar to, and exchanges fluids with, interstitial fluid
• To be able to produce plasma from centrifugation, an anti-coagulant must be added to the blood. This is often pre-added to the test tube when the blood sample is taken, meaning there is anticoagulant already in the tube to prevent clotting.
• Plasma is the fluid that remains when clotting is prevented. Serum is plasma minus the clotting factors and blood cells. During the process of removing the clotting factors (achieved by centrifugation), the protein fibrinogen as described above is converted to fibrin. Fibrin is an insoluble protein that is used to assist in the repair of tissue damage by forming a clot over the wound which acts to hinder the flow of blood. Serum thus is the fluid that remains after coagulation, where the fibrin has been removed.
• Both plasma and serum can be extracted from blood with the use of a centrifuge but it's worth noting that serum is obtained after the clotting of blood, while plasma can be obtained before the coagulation of the blood. Serum is mostly used for blood typing but is also used for diagnostic testing. Plasma on the other hand, is mostly used for blood-clotting related problems.
• Components of Plasma

  • Water 90%
  • Plasma Proteins 6-8%
  • Electrolytes (Na+ & Cl-) 1%
  • Nutrients (e.g. Glucose and amino acids)
  • Hormones (e.g. Cortisol, thyroxine)
  • Wastes (e.g. Urea)
  • Blood gases (e.g. CO2, O2)
• Functions of Plasma

  • Water: Transport medium; carries heat
  • Electrolytes: Membrane excitability, Osmotic distribution of fluid between ECF & ICF, Buffering of pH changes
  • Nutrients, wastes, gases, hormones: No function – just being transported
  • Plasma Proteins: Maintaining colloid osmotic balance (albumins), Buffering pH changes, Transport of materials through blood, Antibodies, Clotting factors
• Cellular Elements of Blood

  • Red Blood Cells
  • White Blood Cells
  • Platelets
• Hematocrit "Packed Cells"

  RBCs heaviest – packed at bottom after centrifugation, Average 45% for men / 42 % for women, Important clinical diagnostic marker, Anemia = Low percentage of erythrocytes i.e low packed cell, Plasma = rest of blood not occupied by RBCs (55% of whole blood for males/ 58% for females)
• RBC'S (Erythrocytes)

  • Shape - a biconcave disc with large surface area, Can change shape, No Nucleus / organelles, Contains hemoglobin, Primary Function = Transport oxygen from the lungs to the cells of the body & assist with CO2 removal
• RBC Structure: Small and highly specialized disc, Thin in middle and thicker at edge, Lack nuclei, mitochondria, and ribosomes, Live about 120 days
• Importance of RBC Shape and Size

  • High surface-to-volume ratio: quickly absorbs and releases oxygen, Discs form stacks: smoothes flow through narrow blood vessels, Discs bend and flex entering small capillaries: 7.8 µm RBC passes through 4 µm capillary
• RBC Fragility

  Erythrocyte fragility refers to the ability of erythrocytes to hemolyse (rupture). RBCs are fragile cells and their shape is maintained by osmotic equilibrium. When RBC are mixed with hypertonic solution, they will shrink, but if mixed with hypotonic they will swell. Both cases (any change in shape) will cause hemolysis. An example of increased osmotic fragility is congenital spherocytosis (RBC's are spherical), Other causes of increase fragility are drugs and infections, deficiency of enzymes(G6PD), all can lyse RBC. The osmotic fragility test is a measure of the ability of the red cells to take up fluid without lysing.
• Mechanism of Transport

  4 Heme Molecules = 4 Oxygen Molecules, Oxygenated Hemoglobin Bright Red (systemic), Deoxygenated Hemoglobin Blue (venous circulation)
• RBC'S (Erythrocytes) cont…

  • Lack intracellular organelles necessary for cellular repair, growth, division, Short Life Span (~120 days), Aged RBC are Fragile - prone to rupture, Ruptured RBC's are destroyed in spleen, Phagocytic WBC's "clear the debris"
• Erythropoiesis

  It is the process of forming RBC. It is stimulated by decrease in number and inhibited by the increase in number of RBC's. Hypoxia is a very potent stimulus for erythropoiesis, and this process is under the influence of erythropoietin
• Too few, Too many

  • Anemia – low hematocrit (below-normal oxygen-carrying capacity of the blood)
  • Nutritional, dietary deficiency of factors needed for erythropoiesis e.g Iron deficiency anemia, Vitamin B12 deficiency (megaloblastic anemia), Aplastic: failure of the bone marrow to produce enough RBC's, Renal: kidney disease (inadequate erythropoietin secretion), Hemorrhagic: loss of a lot of blood, Hemolytic:rupture of too many RBCs
• Polycythemia- abnormally high hematocrit (too many RBCs in circulation)

  • Relative polycythemia due to reduction in plasma volume
  • Primary:(Polycythemia Vera) erythropoiesis proceeds at an excessive, uncontrolled rate, not subjected to normal erythropoietin regulatory mechanism
  • Secondary: an appropriate erythropoietin-induced adaptive mechanism to improve blood's oxygen carrying capacity in response to a prolonged reduction in oxygen delivery to the tissues
• Physiological Factors influencing RBC number

  • RBC count is very high at birth, The count is higher in children than in adults, RBC count is raised at high altitude, in warm temperature, during excitement, In women RBC count is relatively low during pregnancy, A fall in RBC count is seen low altitude
• Pernicious : inability to absorb enough ingested vitamin B12 from the digestive tract (deficiency of intrinsic factor), which is secreted by gastric mucosa and is bound to B12 so that to protect it from digestive enzymes and also assists in absorption of vitamin B12 in the ileum, so megaloblastic anemia develops
• Red marrow

  Active cellular marrow
• Yellow marrow

  Inactive marrow that is infiltrated with fat
• Hemopoiesis

  1. Formation of blood cells

  2. Occurs at different anatomical sites during the course of development from embryonic to adult life
• Sites of hemopoiesis

  • Yolk sac (early embryonic life)
  • Liver and lymph nodes/spleen (after 3rd month of pregnancy)
  • Bone marrow (from 20th week of embryonic life)

  
• In children, blood cells are actively produced in the marrow cavities of all the bones (axial and extremities)
• By age 18-20, the marrow in the cavities of the long bones become inactive. It will be confined to the axial skeleton like skull, vertebral column, hip, ribs (membranous bone) except for the proximal ends of humerus and femur
• In adults, extramedullary hemopoiesis (liver, spleen) may occur in diseases in which the bone marrow becomes destroyed or fibrosed
• In certain pathological states, when there is increased demand for blood cell production, red marrow reappears in the shafts of the long bones, replacing the fat
• Hematopoietic stem cells (HSCs)

  • Bone marrow cells that are capable of producing all types of blood cells
  • They differentiate into one or another type of committed stem cells (progenitor cells)
  • These in turn form the various differentiated types of blood cells
• HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted
• Neutrophils and monocytes arise from a common precursor
• The bone marrow stem cells are also the source of osteoclasts, Kupffer cells, mast cells, dendritic cells, and Langerhans cells
• The HSCs are derived from uncommitted, totipotent stem cells that can be stimulated to form any cell in the body
• Hematopoietic stem cell transplantation

  Involves taking donated stem cells and giving them to a recipient, so that the recipient can make his or her own new red blood cells, white blood cells, and platelets that help blood to clot