BSC2086 Lecture 6 - The Circulatory System: Blood and Erythrocytes

Functions of Blood

  • Circulatory System: Comprises the heart, blood vessels, and blood.
  • Cardiovascular System: Refers specifically to the heart and blood vessels.
  • Fundamental Role of Blood: To transport substances throughout the body.
  • Specific Functions:
      - 1) Transport various substances including Oxygen (O2), Carbon Dioxide (CO2), nutrients, waste products, and hormones primarily via red blood cells (RBCs).
      - 2) Protection against disease and foreign substances facilitated by white blood cells (WBCs).
      - 3) Regulation of water and pH levels in the body.
  • Vital Nature: Notable that excessive loss of blood can be fatal.

General Properties of Blood

  • Characteristic Values for Healthy Adults:
      - Mean fraction of body weight: 8%
      - Blood volume in adults:
        - Females: 4-5 L
        - Males: 5-6 L
      - Volume per body weight: 80-85 mL/kg
      - Mean temperature: 38°C (100.4°F)
      - pH: 7.35-7.45
      - Viscosity (relative to water): Whole blood is 4.5-5.5; plasma is 2.0
      - Osmolarity: 280-296 mOsm/L
      - Mean salinity: 0.9%
      - Hematocrit (packed cell volume):
        - Females: 37-48%
        - Males: 45-52%
      - Hemoglobin:
        - Females: 12-16 g/dL
        - Males: 13-18 g/dL
      - Mean RBC count:
        - Females: 4.2-5.4 million/μL
        - Males: 4.6-6.2 million/μL
      - Platelet count: 130,000-360,000/μL
      - Total WBC count: 5,000-10,000/μL

Components of Blood

  • Overall Blood Composition:
      - Adults typically have 4-6 L of blood consisting of:
        - Plasma: the clear extracellular fluid.
        - Formed Elements: includes blood cells (both red and white) and platelets.
  • Centrifugation of Blood: Blood can be separated via centrifugation:
      - 55% Plasma
      - 45% RBCs (Hematocrit)
      - < 1% WBCs and platelets (termed the buffy coat on top of the RBC layer).

Blood Plasma

  • Definition: Liquid portion of blood containing:
      - Water, proteins, nutrients, nitrogenous wastes, electrolytes, hormones, and gases.
  • Serum: Remaining fluid after plasma clots.
  • Proteins in Plasma (more abundant solute, 6-9 g/dL):
      - All formed by the liver except for gamma globulins (produced by plasma cells).
      - Types of Proteins:
        - Albumins: Most abundant; contribute to viscosity and osmolarity, influence blood pressure, flow, and fluid balance.
        - Globulins (antibodies): Provide immune functions; includes alpha, beta, and gamma globulins.
        - Fibrinogen: Precursor of fibrin, assists in clot formation.
      - Nutrients: Absorbed through the digestive tract.
      - Nitrogenous Wastes: By-products of protein metabolism like urea.
      - Electrolytes: Majorly comprise sodium (Na+), which influences blood pressure.

Blood Component Breakdown

  • Water: 92% by weight
  • Proteins Total: 6-9 g/dL
  • Albumins: contribute to about 60% of total proteins, with values ranging from 3.2-5.5 g/dL.
  • Globulins: 36% of total proteins (ranged from 2.3-3.5 g/dL).
  • Fibrinogen: 4% (between 0.2-0.3 g/dL).
  • Nutrient values, electrolytes, and trace elements outlined with specifics based on healthy adult averages:
      - Glucose (Dextrose): 70-110 mg/dL
      - Amino Acids: 33-51 mg/dL
      - Lactic Acid: 6-16 mg/dL
      - Total Lipids: 450-850 mg/dL
      - Cholesterol: 120-220 mg/dL
      - Triglycerides: 190-420 mg/dL

Starvation and Plasma Protein Deficiency

  • Hypoproteinemia: Can arise from conditions like starvation, liver & kidney diseases, or burns leading to protein loss.
  • Effects: Results in lowered osmolarity; blood loses more water to tissues than it can absorb by osmosis, leading to tissue swelling (edema) and abnormal fluid accumulation in the abdominal cavity (ascites).
  • Kwashiorkor: A severe dietary protein deficiency condition characterized by:
      - Lack of muscle (especially in arms & legs).
      - Shiny skin and swelling of the abdomen due to ascites leading to risks such as diarrhea and dehydration.

Blood Cell Production - Hemopoiesis

  • Hemopoiesis: The process of blood production, approximating 400 billion platelets, 200 billion RBCs, and 10 billion WBCs daily.
  • Hemopoietic Tissues: Initially present in the yolk sac during the embryonic development, stem cells migrate to bone marrow, liver, spleen, and thymus (the latter three stop postnatal, with spleen being a lifelong lymphocyte producer).
  • Stages of Hemopoiesis:
      - Myeloid Hemopoiesis: Blood formed in the bone marrow.
      - Lymphoid Hemopoiesis: Blood formed within lymphatic organs.
  • Pluripotent Stem Cells (PPSC): Also referred to as hemocytoblasts, these have the potential to develop into multiple cell types, some becoming specialized as colony-forming units (CFUs).

Nutritional Needs for Erythropoiesis

  • Vitamin B12 and Folic Acid: Crucial for rapid cell division.
  • Vitamin C and Copper: Serve as cofactors for enzymes involved in red blood cell synthesis.

Erythrocytes (RBCs) Form and Function

  • Structure: Disc-shaped with a thick rim, measuring 7.5 μM in diameter and 2.0 μm thick at the rim.
  • Lack of Organelles: RBCs generate ATP via anaerobic respiration, preventing the use of O2 being transported.
  • Membrane Structure: Blood type is determined by surface glycoproteins and glycolipids, with cytoskeletal proteins (spectrin & actin) enhancing membrane durability.
  • Cytoplasm: Comprises 33% hemoglobin (Hb), essential for O2 delivery and CO2 transport.
  • Biconcave Shape: Enhances surface area-to-volume ratio, thereby accelerating diffusion rates.
  • Carbonic Anhydrase (CAH): Catalyzes the formation of carbonic acid from CO2 and water, pivotal for both gas transport and pH balance.

Hemoglobin (Hb) Structure

  • Comprises 4 chains (globins): 2 alpha (141 amino acids) and 2 beta (146 amino acids).
  • Each globin chain conjugates with a heme group, allowing hemoglobin to carry four O2 molecules.
  • About 5% of CO2 is transported bound to globin as opposed to the heme group.
  • Different types of hemoglobin:
      - Most adult Hb is HbA (2 alpha and 2 beta chains).
      - A small fraction (2.5%) is HbA2 (2 alpha and 2 delta chains).
      - Fetal Hb comprises 2 alpha and 2 gamma chains, which have higher oxygen affinity.
  • Packaging of Hb: Needs to be contained within RBCs to avoid osmotic issues; with each RBC containing around 280 million hemoglobin molecules.

Erythrocyte Counts and Measurements

  • Three common hematological measurements regarding RBCs include:
      - Hematocrit (Packed Cell Volume): Percentage of blood volume composed of RBCs—men: 42-52%; women: 37-48%.
      - Hemoglobin Concentration:** men**: 13-18 g/dL; *women*: 12-16 g/dL.
      - *RBC Count*: *men*: 4.6-6.2 million/μL; *women*: 4.2-5.4 million/μL.
  • The values for women are generally lower due to:
      - The stimulating effects of androgens on RBC production.
      - Periodic menstrual blood losses.
      - An inverse relationship between hematocrit and body fat.

Erythrocyte Lifecycle

  • Erythropoiesis: Complete life cycle of an RBC averages 120 days, initiated in bone marrow and concluding in the spleen and other organs.

Erythrocyte Production Process

  • Production Rate: Approx. 2.5 million RBCs per second with a developmental timeframe of 3-5 days.
  • Stages include: 1) Reduction in size, 2) Increase in number, 3) Synthesis of hemoglobin, 4) Loss of nucleus.
  • PPSC to ECFU: The conversion process involves receptors for erythropoietin (EPO) from kidneys, promoting ECFU conversion to erythroblast, followed by multiplication, hemoglobin synthesis, and the eventual development into reticulocyte.

Nutritional Necessities for Erythropoiesis

  • Iron: A fundamental nutrient lost through natural physiological processes; daily requirements are:
      - Men: 0.9 mg/day
      - Women: 1.7 mg/day
      - Needs increase during pregnancy (20-48 mg/day).
  • Iron exists as ferric (Fe3+) and ferrous (Fe2+), with stomach acid facilitating the conversion necessary for absorption. Transport proteins include transferrin and ferritin.
  • Vitamin B12 & Folic Acid: Essential for cell division and nucleus synthesis.
  • Vitamin C & Copper: Cofactors necessary for optimal erythropoietin synthesis.

Erythrocyte Homeostasis and Feedback Control

  • RBC count is controlled through a negative feedback mechanism; a drop in count (e.g., due to hemorrhaging) results in hypoxemia, prompting the kidneys to increase EPO production and stimulate the bone marrow to increase RBC production within 3-4 days.
  • Other factors contributing to hypoxemia include:
      - Low O2 levels due to high altitudes (where people can have up to 7-8 million/μL) or sudden increases in physical activity (e.g., athletes reaching 6.5 million/μL).
  • Excessive erythropoiesis, such as occurs with conditions like emphysema, can result in polycythemia (overproduction of RBCs) without the kidney's awareness.

Erythrocyte Recycle and Disposal

  • Following 120 days in circulation, fragile RBCs undergo hemolysis, primarily via the spleen, where their membranes are digested by macrophages.
  • Hemoglobin Processing:
      - Globin Portion: Hydrolyzed to amino acids.
      - Heme: Iron is separated and converted to biliverdin, subsequently to bilirubin, to be either utilized for new hematopoiesis or secreted into bile by the liver.
  • Jaundice: Occurs from rapid hemolysis, liver disease, or bile duct obstructions leading to bilirubin excess.

Erythrocyte Disorders

  • Types of Disorders:
      - Polycythemia: Excessive RBC count.
        - Primary Polycythemia: Cancer causing overproduction in the red bone marrow; RBC count can exceed 11 million/μL with hematocrit around 80%.
        - Secondary Polycythemia: Caused by dehydration, smoking, high altitudes, etc.; RBC count can be up to 8 million/μL.
      - Anemia: Insufficient RBC production or hemoglobin content, leading to tissue hypoxia.
        - Types include Hemorrhagic, Hemolytic, Hypoplastic, and Nutritional Anemia (Iron-Deficiency & Pernicious Anemia).
      - Sickle Cell Disease: A hereditary condition affecting approximately 1.3% of African Americans, where the genetic mutation alters hemoglobin structure leading to defective RBCs.

Sickle Cell Disease Details

  • In sickle cell disease, hemoglobin S (HbS) does not bind O2 effectively and differs from normal hemoglobin A (HbA) in one amino acid of the beta chain.
  • Physiologically, hypoxia leads to polymerization of HbS, resulting in elongated, sickle-shaped cells, which causes vascular occlusions.
  • Complications include severe pain, kidney and heart failure, paralysis, and stroke, with augmented lymphocyte production prompting splenic and cranial bone growth.
  • A notable aspect of these patients is partial resistance to malaria due to the inability of the Plasmodium organism to effectively digest sickle hemoglobin.

Blood Types: Antigens and Antibodies

  • Discovery: Karl Landsteiner elucidated blood types in 1900.
  • Antigens and Antibodies:
      - Antigens: Unique molecules enabling the identification of self versus foreign substances; foreign antigens incite immune responses.
      - Antibodies: Generated by plasma cells in response to foreign invaders.
  • Blood Grouping:
      - The ABO blood group system categorizes blood presence/absence of antigens A and B, with types A, B, AB, and O determined by their respective antigen profiles.

Blood Typing and Transfusions

  • Antibody formation against foreign antigens begins 2-8 months postnatally and peaks around 8-10 years.
  • The body produces antibodies corresponding to the antigens it lacks; type O is the universal donor, while type AB is the universal recipient due to their absence or presence of antibodies, respectively.
  • In transfusions, compatibility is critical to avoid agglutination and hemolysis; mismatched transfusions can lead to life-threatening complications including renal failure.
  • Transfusion Tests: Involve adding blood to specific antibodies pools to identify the corresponding blood type through observed agglutination patterns.

Rh Group and Hemolytic Disease of Newborns

  • Rh Factor: Discovered in rhesus monkeys, indicating Rh+ blood types contain D agglutinogens on their RBCs. Rh factor frequencies vary among ethnic populations.
  • Hemolytic Disease of Newborns: Results from Rh- mothers forming anti-D antibodies due to prior exposure to Rh+ blood, endangering subsequent Rh+ pregnancies through placental transmission leading to hemolysis of fetal RBCs.
  • Preventative Measures: RhoGAM administration during pregnancy to Rh- women helps prevent the formation of these antibodies.
  • Treatment strategies involving UV light or exchange transfusions can alleviate severe conditions postnatally.