5.1 Lecture - Red Blood Cells: Function, Concentration, Production

• Red blood cells (erythrocytes) primarily transport hemoglobin, which carries oxygen
• Hemoglobin in humans must be contained within red blood cells to prevent loss through kidney filtration
• Red blood cells contain carbonic anhydrase, acting as an effective acid-base buffer

Red Blood Cell Concentrations

• Men average 5.2 million red blood cells per microliter
• Women average 4.7 million red blood cells per microliter
• Hemoglobin concentration maxes out at 34g per 100ml of cells due to metabolic limits
• Whole blood contains 15g of hemoglobin per 100ml in men with normal hematocrit
• Whole blood contains 14g of hemoglobin per 100ml in women with normal hematocrit
• Each gram of hemoglobin can bind with 1.3ml of oxygen when fully saturated

Red Blood Cell Production

• In early embryonic life: yolk sac
• Middle trimester: spleen and lymph nodes
• Last month of gestation: bone marrow
• By 5 years old and below: bone marrow of all bones
• From 5 to 20 years old: long bones
• After 20 years old: membranous bones (vertebrae, sternum, ribs, ilium)

Red Blood Cell Genesis

• All blood cells originate from hematopoietic stem cells in bone marrow
• Growth inducers and differentiation inducers control their life cycle
• Interleukin-3 promotes growth of all types of committed stem cells
• Low oxygen levels induce growth and differentiation, increasing red blood cell production
• Red blood cells development: proerythroblast to reticulocyte to erythrocyte
• Reticulocytes can pass from bone marrow into blood capillaries
• Reticulocytes mature into erythrocytes within 1-2 days
• Reticulocyte concentration is normally less than 1% of red blood cells due to their short lifespan

Red Blood Cell Volume

• Red blood cell volume must be within a narrow range for optimal oxygen transport and blood flow
• Erythropoietin regulates red blood cell production based on tissue oxygenation
• Tissue hypoxia, not red blood cell concentration, controls production
• Kidneys produce 90% of erythropoietin, liver produces 10%
• Renal hypoxia increases transcription of the erythropoietin gene
• Hypoxia in other tissues stimulates erythropoietin production through norepinephrine, epinephrine, and prostaglandins
• Erythropoietin stimulates proerythroblast production from hematopoietic stem cells within minutes to hours
• New red blood cells appear in circulation about 5 days later

Red Blood Cell Maturation

• With sufficient erythropoietin, iron, and nutrients red cell production can increase to ten times normal
• Vitamin B12 and folic acid deficiencies impair DNA and nuclear maturation and cell division, affecting red blood cell production

Pernicious Anemia

• Pernicious anemia results from gastric cancer abnormalities that prevent normal gastric secretions
• Parietal cells produce intrinsic factor which protects vitamin B12 from digestion
• Intrinsic factor binds to cells in the ileum to facilitate B12 absorption Lack of intrinsic factor reduces available B12

Hemoglobin

• Adult hemoglobin (hemoglobin A) consists of four hemoglobin chains, each with a heme group containing one iron atom
• Each iron atom binds one oxygen molecule loosely and reversibly
• Variations in amino acid composition of peptide chains can alter oxygen-carrying capacity, such as in sickle cell anemia

Iron

• The average total iron quantity in the body is 4-5g
• It is absorbed in the small intestine
• Excess iron stored in liver hepatocytes
• Macrophages break down hemoglobin from old red blood cells, storing iron in the ferritin pool for reuse
• Men lose about 0.6mg of iron daily in feces
• Women lose about 1.3mg of iron daily, accounting for menstruation
• Intestinal iron absorption is limited, even with high ingestion
• Absorption decreases when the body is saturated with iron

Red Blood Cell Lifespan

• The lifespan of red blood cells is 120 days
• Mature red blood cells lack a nucleus, mitochondria, and endoplasmic reticulum
• Cytoplasmic enzymes metabolize glucose and form ATP
• They maintain cell membrane pliability, transport ions, and keep iron in the ferrous state
• Enzyme activity decreases with age, increasing fragility
• Red blood cells often self-destruct in the spleen
• Spleen's narrow passageways (3 micrometers) trap fragile cells
• Splenectomy increases the number of old, abnormal red blood cells in circulation

Anemia

• Blood loss anemia
• Aplastic Anemia
• Megaloblastic Anemia
• Hemolytic Anemia

Blood Loss Anemia

• Rapid blood loss quickly replaced within 1-3 days
• Red blood cell concentration returns to normal in 3-6 weeks
• Chronic blood loss causes microcytic hypochromic anemia due to insufficient iron absorption

Aplastic Anemia

• Aplastic anemia results from bone marrow dysfunction
• Causes: high dose radiation, chemotherapy, toxic chemicals (insecticides, benzene), autoimmune disorders (lupus)
• Idiopathic aplastic anemia occurs in about 50% of cases, cause unknown

Megaloblastic Anemia

• Megaloblastic anemia involves large, misshapen red blood cells (megaloblasts)
• Caused by vitamin B12, folic acid, or intrinsic factor deficiency
• Megaloblastic cells rupture easily, leading to anemia

Hemolytic Anemia

• Hemolytic anemia involves fragile red blood cells that rupture easily, especially in the spleen
• Red blood cell production may be normal or high, but lifespan is short
• Types: hereditary spherocytosis, sickle cell anemia, erythroblastosis fetalis

Hereditary Spherocytosis

• Red blood cells are small and spherical instead of biconcave

Sickle Cell Anemia

• Faulty beta chains in hemoglobin
• Low oxygen causes chains to precipitate into long crystals inside the red blood cells
• This causes cells to become fragile

Sickle Cell Crisis

• a progressive cycle resulting from low oxygen tension
• Low oxygen leads to sickling and rupture of red blood cells
• Results in decreased oxygen tension and further rupture

Erythroblastosis Fetalis

• Occurs when RH positive red blood cells in a fetus are attacked by antibodies from an RH negative mother
• Antibodies cause the RH positive cells to become fragile, leading to rupture and anemia

Circulatory Effects of Anemia

• Reduced blood viscosity due to lower red blood cell concentration
• Viscosity decreases from 3 times that of water to as low as 1.5 times
• Decreased viscosity reduces resistance, increasing blood flow and cardiac output
• Hypoxia from diminished oxygen transport dilates peripheral blood vessels, further increasing cardiac output
• Increased cardiac workload can lead to cardiac failure
• Increased cardiac output offsets reduced oxygen-carrying capacity unless further demand occurs

Polycythemia

• Secondary polycythemia results from tissue hypoxia and increased red blood cell production
• Causes: high altitudes, impaired oxygen delivery (cardiac failure)

Polycythemia Vera

• Polycythemia vera is caused by a genetic mutation in hemopoietic cells
• Red blood cell production does not stop at sufficient quantities
• Marked increase in red blood cell mass and blood volume
• Blood volume can double, viscosity increases to ten times that of water
• Causes a ruby complexion from increased blood in skin venous plexus and a bluish tint from cyanosis

Circulatory Effects of Polycythemia

• Sluggish blood flow decreases venous return to the heart
• Increased blood volume increases venous return
• Cardiac output remains almost normal due to balancing effects
• Compensatory mechanisms are typically intact
• Hypertension in only one-third of polycythemia vera cases

Explore red blood cell function, including hemoglobin transport and acid-base buffering. Understand typical red blood cell and hemoglobin concentrations in men and women. Learn about red blood cell production in different stages of life, from embryonic development to adulthood.