Human Physiology: Erythrocytes and Hematopoiesis

Anatomy & Physiology I - Lecture 11 - Blood (Part 1)

• Course: ANP 1105A
• Topic: Basic cellular physiology, anatomy, and physiology of the cardiovascular, lymphatic, and respiratory systems.
• Specific focus: Blood (part 1)
• Presenter: Dr. Stephen Gee

Readings - Marieb and Hoehn 11th Edition, Chapter 17 (pp. 642-666)

• Blood functions: Transport, regulation, and protection
• Blood composition: Plasma and formed elements
• Erythrocytes (red blood cells): Crucial for oxygen and carbon dioxide transport
• Platelets: Cell fragments aiding in stopping bleeding
• Hemostasis: Prevents blood loss
• Transfusion: Replaces lost blood

Overview: Chapter 17 Blood

• Blood as the body's internal transport system
• Blood function questions: What does blood do?, What is blood made of?, What happens when a blood vessel breaks?, How do we replace blood in an emergency?, What can the study of blood tell us about a patient?
• Blood composition: Plasma, formed elements (erythrocytes, leukocytes, and platelets)

Blood - Internal Transport System

• Blood is the life-sustaining transport vehicle of the cardiovascular system
• Circulatory pathways: Pulmonary circulation and systemic circulation
• Components: Heart, arteries, veins, and capillaries
• Oxygen-rich (red) and oxygen-poor (blue) blood

Functions of Blood

• Transport: Oxygen, nutrients, metabolic wastes (CO2 and urea), hormones from endocrine glands to targets.
• Regulation: Body temperature, heat distribution, pH buffering (bicarbonate), fluid volume.
• Protection: Proteins and platelets initiate clot formation to prevent blood loss, antibodies, complement proteins, and white blood cells fight infection.

Composition of Blood

• Fluid connective tissue
• Matrix: Plasma (liquid portion)
• Cells: Formed elements (erythrocytes, leukocytes, platelets)
• Plasma components: Amino acids, nutrients, proteins (albumins, globulins, fibrinogen), gases, electrolytes, nitrogenous waste
• Formed elements: Platelets, leukocytes (granulocytes and agranulocytes), erythrocytes

Centrifugation of Whole Blood

• Yields three layers: Hematocrit, Buffy coat, Plasma
• Hematocrit: Normal values for males and females (M: 47 +/- 5%; F: 42 +/- 5%).
• Buffy coat: Thin, whitish layer between RBCs and plasma (low percentage, < 1%)
• Plasma: ~55% of whole blood (most abundant portion).

Physical Characteristics and Volume

• Sticky, opaque fluid with a metallic taste
• Color varies with oxygen content (oxygen-rich: scarlet; oxygen-poor: dark red)
• Slightly alkaline pH (7.35-7.45)
• Denser than water, 5x viscosity (mostly due to RBCs)
• ~8% of total body weight
• Average volumes: Males (5-6 L), Females (4-5 L)

Blood Plasma

• Straw-colored, sticky fluid (mostly water - 90%)

• 100 dissolved solutes

• Major components (plasma proteins, electrolytes, nutrients, gases, hormones, wastes, and inorganic ions)
• Plasma proteins are the most abundant solutes
• Albumin (60%): Plasma protein, carrier, blood buffer, contributes to plasma osmotic pressure.

Formed Elements

• RBCs (erythrocytes), WBCs (leukocytes), platelets
• Only WBCs are complete cells
• RBCs lack nuclei and organelles
• Platelets are cell fragments
• Survival in bloodstream (days)
• Originate in bone marrow, do not divide.

Erythrocytes - Structural Characteristics

• Small diameter (7.5 µm) cells
• Biconcave disc shape, anucleate, and no organelles
• Contain hemoglobin (Hb) for gas transport
• RBC diameters exceed some capillaries (spectrin and other PM proteins allow flexibility)
• Features for efficient gas transport (biconcave shape - large surface area to volume ratio for gas exchange, and 97% Hb)
• No mitochondria (anaerobic metabolism)

Erythrocyte Function

• Respiratory gas transport: Hemoglobin (Hb) binds reversibly with oxygen.
• Normal values for Hb concentration (Males 13-18 g/100ml; Females 12-16 g/100ml)
• Hemoglobin (Hb) structure: Heme pigment bound to Globin protein (α and β chains)
• Hb binds oxygen in lungs (Oxyhemoglobin); unloads it in tissues (Deoxyhemoglobin or reduced hemoglobin); and binds carbon dioxide in tissues (carbaminohemoglobin).

Erythropoiesis

• Formation of red blood cells
• Occurs in red bone marrow
• Regulated by Erythropoietin (EPO) from Kidneys
• Stages: Hematopoietic stem cells to committed cells, to immature forms and mature forms through ribosome synthesis and hemoglobin accumulation.

Regulation of RBC Production by Erythropoietin

• Kidneys regulate erythropoiesis through EPO (erythropoietin)
• EPO is produced in response to low oxygen, such as at high altitudes; some athletes artificially increase EPO for athletic performance, but health risks possible
• Feedback loop maintaining consistent RBC production.

Erythropoiesis Dietary Requirements

• Nutritional needs for RBC production, including iron, amino acids, lipids, and carbohydrates.
• Iron availability from diet; stored in cells as ferritin or hemosiderin, and transported in blood as transferrin.
• Vitamins B12 and folic acid for DNA synthesis in RBC development.

Erythrocyte Fate

• Life span: 100-120 days
• Old RBC breakdown (heme, iron, globin separated)
• Heme is degraded to bilirubin; liver secretes bilirubin into intestines; converted to stercobilin (excreted via feces)
• Globin is metabolized to amino acids for reuse.

Erythrocyte Disorders

• Anemia (too few RBCs) and Polycythemia (too many RBCs)
• Anemia types: Blood loss (acute or chronic); insufficient production; too much destruction.
• Polycythemia types: Primary (bone marrow cancer); Secondary (due to low oxygen or EPO production). Blood doping is an artificial method to increase RBC and EPO.

Anemia – Blood Loss

• Acute hemorrhagic anemia: Rapid blood loss. Treated by blood replacement
• Chronic hemorrhagic anemia: Slight, persistent blood loss. Treat the underlying cause like ulcers or hemorrhoids.

Anemia - RBC Production Defects

• Iron-deficiency anemia: Hemorrhage, low Fe intake, impaired absorption. Treatment with iron supplements.
• Pernicious anemia: Autoimmune - destroys stomach mucosa (needed to absorb B12). Treatment: Intramuscular B12 injections or nasal gel.
• Renal anemia: Kidneys cannot produce enough EPO. Treatment: synthetic EPO.
• Aplastic anemia: Destruction/inhibition bone marrow function. Treatment: Short-term: transfusion; Long-term: HSCs.

Anemia – RBC Destruction

• Hemolytic anemia: Premature RBC lysis.
• Hb abnormalities: Thalassemia and Sickle-cell anemia (genetic defects in globin). Sickle-cell anemia provides protection against malaria in some individuals.
• Methods of treatment for abnormal hemoglobins and other disorders include incompatible transfusions, infections.

Polycythemia

• Excess RBCs; increased blood viscosity; sluggish blood flow
• Polycythemia vera: Bone marrow cancer - Treatment: therapeutic phlebotomy
• Secondary polycythemia: Low O2 levels (high altitude) or EPO overproduction
• Blood doping (artificial EPO or RBCs for stamina enhancement) is an ethical concern for athletes.

Platelets (thrombocytes)

• Platelets are megakaryocyte fragments
• Light blue-staining outer region, purple granules
• Contain clotting chemicals (serotonin, calcium, enzymes, ADP, platelet-derived growth factor)
• Form temporary plugs in injured blood vessels
• Kept inactive and mobile via nitric oxide and prostacyclin from endothelial cells.

Platelet Formation (Thrombopoiesis)

• Regulated by thrombopoietin (liver, kidneys)
• Originate from megakaryoblasts (myeloid line blood cells)
• Mitoses occurs, but no cytokinesis, to produce large, multilobed megakaryocytes. Projections from megakaryocytes are a route for platelets to detach into the blood vessel lumen.

Platelets

• Stage IV megakaryocytes contact marrow sinusoids and send cytoplasmic projections (podosomes) into capillaries to release platelets.
• Platelets live about 10 days
• Normal platelet count: 150,000-400,000 platelets/µL blood.

Summary of Formed Elements

• Table summarizing different blood cell types: Erythrocytes (red blood cells), Leukocytes (white blood cells), Granulocytes (neutrophils, eosinophils, basophils) and Agranulocytes (lymphocytes, monocytes), and Platelets
• Includes illustrations, descriptions, cell count/µL of blood, and duration/life span of development.

Hematopoiesis in Humans

• Detailed diagram outlining the processes of blood cell formation from the hematopoietic stem cell through stages in bone marrow, including different lineages and formed cell types.