Chapter 14

• Blood


  • Only type of connective tissue with a liquid matrix (plasma)
  • Transports vital substances, regulates processes for homeostasis
  • Regulates stability of interstitial fluid (volume and pH)
  • Distributes heat
  • Protects - blood loss and infection

  
• Adult blood volume is about 4 to 5 liters in a female and 5 to 6 liters in a male
• Blood cells


  • Red blood cells (RBCs)
  • White blood cells (WBCs)
  • Platelets (cell fragments)

  
• Plasma


  • Clear, straw-colored fluid matrix of blood
  • About 55% of blood volume, 91% water

  
• Hematocrit


  Percentage of RBCs in blood

  
• Serum


  • Blood minus RBCs after it has clotted
  • Lacks the coagulation factors
• Plasma


  Blood minus RBCs before it has clotted
• Universal precautions


  • A set of specific safety measures taken to prevent transmission of bloodborne pathogens
  • Mainly used for HIV, Hepatitis B virus
  • Assume any patient may have been exposed to bloodborne pathogens
  • Estimated that 4 to 7% of new cases of infectious disease are transmitted by unsafe injections
• Universal precautions recommendations


  • Engineering controls
  • Use of personal protective equipment
  • Use of fume hoods and sharps containers
  • Safe workplace practices
• Hematopoiesis


  • Formation of blood cells (formed elements consist of RBCs, WBCs, and platelets)
  • Blood cells originate in red marrow from hematopoietic stem cells

  
• Hematopoietic stem cells give rise to

  • More stem cells
  • More specialized or differentiated cells in response to hematopoietic growth factors

  
• Cells derived from hematopoietic stem cells

  • Lymphoid stem cells: Give rise to lymphocytes
  • Myeloid stem cells: Give rise to all other types of formed elements: Red blood cells, other types of white blood cells, and platelets

  
• Red blood cells (RBCs)

  • Biconcave disc shape
  • Excellent for gas exchange
  • Carry oxygen and carbon dioxide
  • Consist of one-third hemoglobin
  • Lack nuclei and mitochondria
  • Produce ATP through glycolysis
  • Cannot divide - Average life span of RBC is 120 days

  
• Erythropoiesis


  1. RBC formation occurs in red bone marrow

  2. Regulated by a negative feedback mechanism

  3. Low blood O2 causes kidneys and liver to release EPO (erythropoietin), which stimulates RBC production

  4. Many new RBCs appear in the blood within a few days of EPO secretion
• Nutritional requirements for erythropoiesis

  • Vitamin B12 and folic acid: Required for DNA synthesis; necessary for the growth and division of all cells
  • Iron: Required for hemoglobin synthesis
• Anemia


  Condition in which the O2-carrying capacity of the blood is reduced, due to deficiency of RBCs or hemoglobin

  
• Hemoglobin (Hb)


  • Protein in RBCs that carry oxygen
  • Heme (red) group bound to globin chain (4 in total)
  • Each heme group has an iron molecule
  • Each Hb molecule can carry 4 oxygen molecules
  • 1 RBC has 250 million Hb molecules = 1 billion oxygen molecules per RBC
  • Oxygen on Hb - oxyhemoglobin
  • No oxygen on Hb - deoxyhemoglobin
  • Normal range: 14 – 18 g/dL males, 12 -16 g/dL females

  
• Sickle cell disease


  • Caused by a single DNA base mutation
  • RBCs are sticky, deform into sickle shapes, and block narrow blood vessels, stopping blood flow to local areas
  • Oxygen deficiency leads to more sickling, more blockages, severe pain
  • RBCs die quickly, resulting in anemia, which causes extreme fatigue

  
• Sickle cell disease treatment

  1. Children diagnosed at birth receive antibiotics to protect infection in spleen

  2. Hydroxyurea given to cause production of fetal hemoglobin, which is more efficient at binding oxygen; slows down sickling

  3. Transplant of bone marrow or umbilical cord stem cells can cure disease

  4. Experiments to correct the mutation in the genome and infuse new stem cells into bone marrow show promise
• • SCD affects approximately 100,000 Americans
  • SCD occurs among about 1 out of every 365 Black or African-American births
  • SCD occurs among about 1 out of every 16,300 Hispanic-American births
• 1 copy of sickle cell trait (not the disease)

  Have a better chance of surviving malaria
• RBCs sickle when infected with malaria


  Does not survive in the body as well
• RBC death


  • After months of bending and squeezing through narrow capillaries, RBCs lose elasticity and become fragile
  • Worn out or damaged RBCs are removed by spleen or liver
  • Ruptured RBCs are phagocytized by macrophages: Hemoglobin separates into 4 subunits: globin chains with heme groups, Heme groups break down into iron and biliverdin, Iron is transported to red bone marrow by the protein transferrin, Biliverdin is converted into bilirubin
• White blood cells (Leukocytes, WBCs)

  • Protect against disease
  • Leukocytes have limited life spans, so they must always be replaced
  • Produced in red bone marrow, under control of hormones: interleukins and colony-stimulating factors
• Types of WBCs


  • Granulocytes, which have granular cytoplasm, and short life span: Neutrophils, Eosinophils, Basophils
  • Agranulocytes, which do not have noticeable granules: Lymphocytes, Monocytes
• Functions of WBCs


  • Diapedesis: WBCs can squeeze between the cells of a capillary wall and leave blood vessel, then migrate toward infection site
  • Cellular adhesion molecules: proteins that direct leukocytes to injury sites
  • Phagocytosis: Engulfing and digestion of pathogens; neutrophils and monocytes are most mobile and active phagocytes
  • Inflammatory response: Reaction that restricts spread of infection; promoted by basophils, by secretion of heparin and histamine; involves swelling and increased capillary permeability
  • Positive chemotaxis: Attraction of WBCs to an infection site, by chemicals released by damaged cells
• WBC types


  • Neutrophils – 1st to arrive at infection (54%-70% of WBCs)
  • Eosinophils – Elevated in response to parasitic worm infestations and allergic reactions (1%-3% of WBCs)
  • Basophils – release heparin and histamine (<1% of WBCs)
  • Lymphocytes – important for immunity, T and B cells (25% - 33% of WBCs)
  • T cells – attack pathogens and tumor cells
  • B cells – produce antibodies
  • Monocytes – phagocytize bacteria, dead cells and debris (3%-9% of WBCs)
• Plasma


  • Contains organic and inorganic chemicals
  • Transports nutrients, gases, hormones, and vitamins
  • Helps regulate fluid and electrolyte balance and maintain pH
• Oxygen and carbon dioxide


  Most important blood gases
• Plasma electrolytes


  • Ions that ionize in water and can conduct electricity
  • Absorbed from the intestine or released as by-products of cellular metabolism
  • Sodium and chloride are most abundant electrolytes
• Platelets (thrombocytes)


  • Cytoplasmic fragments of megakaryocytes
  • Produced by hemocytoblasts in response to the hormone, thrombopoietin
  • Lack a nucleus, and are less than half the size of a RBC
  • Platelet count: 150,000 to 400,000/µL of blood
• Platelets


  • Help in hemostasis (stoppage of bleeding) in damaged blood vessels, by sticking to broken surfaces
  • Release serotonin, which causes smooth muscles in walls of broken blood vessels to contract
• Hemostasis


  • Stoppage of bleeding
  • Actions that limit or prevent blood loss include: Blood vessel (vascular) spasm, Platelet plug formation, Blood coagulation
  • Most effective in small blood vessel injuries
• Vascular spasm


  • Stimulated by cutting or breaking a small blood vessel
  • Smooth muscle in blood vessel contracts rapidly
• Platelet plug formation


  • Triggered by exposure of platelets to collagen
  • Platelets adhere to rough surface to form a plug
• Blood coagulation


  1. Most effective hemostatic mechanism, occurs within 5 to 15 minutes

  2. Form blood clot in a series of reactions, in which each step activates next one (a cascade)

  3. Many chemicals used in coagulation are called clotting factors

  4. Vitamin K necessary for functioning of some of the clotting factors

  5. Major event is conversion of soluble fibrinogen to insoluble threads of fibrin, which traps blood cells

  
• Fate of blood clots

  • After a blood clot forms, it retracts and pulls the edges of a broken blood vessel together while squeezing serum from the clot
  • Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls
  • Plasmin digests fibrin threads, and dissolves the blood clot

  
• Abnormal blood clot formation

  • Thrombus: An abnormal blood clot that forms in a blood vessel
  • Thrombosis: Blood clot in a vessel supplying a vital organ (brain, heart)
  • Embolus: A blood clot moving through the blood vessels
  • Embolism: Blood clot that travels, and then blocks a blood vessel in an organ (such as pulmonary embolism in lungs)
  • Infarction: Death of tissues which have blocked blood vessels due to blood clot formation
  • Atherosclerosis: Accumulation of fat in arterial linings can sometimes cause abnormal clot formation; a common form of thrombosis

  
• Blood groups and transfusions

  • Blood types are distinguished by proteins (antigens) on the surfaces of red blood cells
  • Safe transfusions require knowing the blood types of donor and recipient, and cross matching donor red blood cells (RBCs) with recipient's serum, checking for agglutination (clumping of RBCs)

  
• Blood types


  • Universal donor
  • Universal recipient