U7 RBC

DISORDERS OF RED BLOOD CELLS

The Red Blood Cell

  • Definition: Red blood cells (RBCs), also known as erythrocytes, are the most common type of blood cell, being 500-1000 times more numerous than other blood cells.

  • Functions:

    • Hemoglobin (Hg) within RBCs carries oxygen to the body's tissues.

    • RBCs transport carbon dioxide (CO₂) to be excreted.

    • They contribute to the regulation of acid-base balance.

  • Structure:

    • Mature RBCs are nonnucleated (anucleated) and have a biconcave disc shape.

    • The shape serves two primary oxygen-carrying functions:

    1. Provides a larger surface area for oxygen diffusion.

    2. The thinness of the cell membrane enables rapid diffusion of oxygen between the exterior and innermost regions of the cell.

Hemoglobin and Its Properties

  • Hemoglobin (Hg):

    • RBCs derive their red color from hemoglobin, an iron-containing pigment.

    • Oxygen is poorly soluble in plasma; therefore, 95-98% of oxygen is carried bound to hemoglobin.

  • Flexibility of RBCs:

    • The RBC membrane's flexibility allows for the transport function by enabling easy passage through capillaries.

    • RBCs can change shape to flow through the smallest capillaries to reach peripheral tissues.

    • A complex network of fibrous proteins, particularly spectrin, maintains the flexibility and biconcave form of the RBC membrane.

Structure of Hemoglobin

  • Each hemoglobin (Hg) molecule can carry four (4) molecules of oxygen.

  • Hemoglobin changes color based on its oxygenation state:

    • Appears reddish when oxygen is attached.

    • Appears bluish when deoxygenated.

  • Types of Hemoglobin:

    • Two major types exist:

    1. Adult Hemoglobin (HbA)

    2. Fetal Hemoglobin (HbF), which is generally replaced by HbA by six (6) months of age.

  • Mutations: There are > 550 types of abnormal hemoglobin molecules.

Life Span and Degradation of RBCs

  • RBCs have an approximate lifespan of 120 days, after which they are broken down in the spleen.

  • Recycling: Degradation products such as iron and amino acids are recycled. Damaged RBCs require 120 days for replacement.

Hemoglobin Synthesis

  • Definition: Hemoglobin (Hgb/Hb) is the oxygen-carrying protein of erythrocytes.

    • Comprises approximately 90% of the RBC’s dry weight.

    • A single erythrocyte can contain up to 300 hemoglobin molecules.

Structure of Hemoglobin Molecule

  • Each hemoglobin molecule consists of:

    • Two pairs of polypeptide chains (the globins).

    • Four colorful complexes of iron plus protoporphyrin (the hemes).

  • Synthesis Dependency: The rate of hemoglobin synthesis is dependent on iron availability for heme synthesis. A lack of iron results in low hemoglobin levels in RBCs.

Iron Stores in the Body

  • The amount of stored iron in the body varies:

    • Approximately 2 g in assigned-at-birth females.

    • Up to 6 g in assigned-at-birth males.

  • Iron Distribution:

    • Most body iron (approximately 80%) is found in the heme of hemoglobin.

    • 20% is stored in bone marrow, liver, spleen, and other organs.

    • Small amounts are present in myoglobin of muscles, cytochromes, and iron-containing enzymes

Dietary Iron and Absorption

  • Iron Absorption: Dietary iron helps maintain body stores, primarily derived from meat, absorbed in the duodenum.

  • Response to Body Needs:

    • When iron stores decrease or erythropoiesis is stimulated, iron absorption increases.

    • In cases of iron overload, iron excretion is accelerated.

  • Recycling of Iron: Iron in the hemoglobin compartment is recycled when RBCs are destroyed, with iron being returned to circulation for incorporation into new RBCs or sent for storage in the liver.

Red Cell Production

Erythropoiesis

  • Definition: Erythropoiesis is the process of red blood cell production.

  • Location:

    • Occurs in utero in the bone marrow.

    • After birth, RBCs are produced in the red bone marrow.

    • Up to approximately five years of age, almost all bones produce RBCs to meet the growth needs.

    • Production gradually decreases, and after 20 years of age, mainly occurs in the membranous bones of the vertebrae, sternum, ribs, and pelvis

Precursor Cells

  • RBCs are derived from precursor cells known as erythroblasts, formed continuously from pluripotent stem cells in the bone marrow.

  • These red cell precursors undergo a series of divisions, each producing a smaller cell as they develop into mature RBCs.

  • Hemoglobin synthesis begins at the early erythroblast stage and continues until the cell becomes a mature erythrocyte.

  • The transformation from normoblast to reticulocyte occurs as the RBC accumulates hemoglobin while losing its nucleus

Regulation of Erythropoiesis

  • Approximately 1% of the body’s total complement of RBCs is generated from the bone marrow each day.

  • The time from a stem cell to the emergence of a reticulocyte is about one week, with most maturing red cells entering the blood as reticulocytes.

  • Reticulocyte Count: This count provides an index of erythropoietic activity in the bone marrow.

  • Regulatory Mechanism:

    • Erythropoiesis is largely governed by tissue oxygen needs.

    • Negative feedback occurs when conditions decrease oxygen transport in the blood, leading to increased RBC production

Erythropoietin

  • Oxygen content in the blood does not act directly on the bone marrow to increase RBC production; instead, decreased oxygen content is sensed by peritubular cells in the kidneys, which produce erythropoietin.

  • Under homeostatic conditions, about 90% of all erythropoietin is produced by the kidneys, with 10% produced in the liver.

  • In the absence of erythropoietin, as in renal failure, hypoxia has little to no effect on RBC production.

  • Recombinant Erythropoietin: This can be produced through recombinant DNA technology. Uses include:

    • Treatment of chronic anemia resulting from chronic renal failure.

    • Treatment of anemias induced by chemotherapy.

    • Treatment of anemia in HIV-infected individuals

Red Cell Destruction

  • Mature RBCs have a lifespan of ≤ 120 days. As they age, metabolic activity, enzyme activity, and ATP levels decline. Damaged cells can deteriorate within this time.

  • Carbon monoxide poisoning→ RBC needs replacement and damaged cells leave the body within 120 days & replaced with new cells

  • The destruction process involves:

    • Reduced membrane lipids and increased membrane fragility, leading to self-destruction of RBCs.

    • The rate of self-destruction is normally about 1% per day and equals the production rate. In pathologies like hemolytic anemia, the lifespan is shorter.

  • Facilitation of Destruction: Large phagocytic cells in the spleen, liver, bone marrow, and lymph nodes recognize and ingest old and defective cells, salvaging amino acids from globulin chains and iron from heme units.

  • The heme unit is mainly converted to bilirubin (a waste product) that is insoluble in plasma and transported by plasma proteins.

  • Bilirubin is processed by the liver, conjugated with glucuronide to render it water-soluble, and excreted in bile. Increased bilirubin can lead to bilirubin gallstones

Jaundice

  • Definition: Jaundice is a clinical manifestation related to hyperbilirubinemia, causing yellow discoloration of the skin.

  • Blood Assays:

    • Unconjugated bilirubin (plasma-insoluble): reported as indirect bilirubin.

    • Conjugated bilirubin (plasma-soluble): reported as direct bilirubin

Red Cell Metabolism and Hemoglobin Oxidation

  • Due to the lack of mitochondria, RBCs rely on glucose and the glycolytic pathway for metabolic needs.

  • Anaerobic metabolism of glucose generates ATP needed for normal membrane function and ion transport.

  • Consequences of Deficiencies:

    • Depletion of glucose or functional deficiencies of glycolytic enzymes can lead to premature RBC death.

    • Hereditary deficiency of glucose-6-phosphate dehydrogenase (G6PD deficiency) predisposes cells to oxidative stress and denaturation of hemoglobin.

    • Hemolysis often occurs due to oxidative stress from infections or exposure to specific foods or drugs

Laboratory Tests for RBCs

  • Evaluation through Blood Sample:

    • Red blood cell count measures the total number of RBCs in a microliter (µL) of blood.

    • Reticulocyte percentage (normally around 1%) indicates the rate of RBC production.

    • Hemoglobin (grams per deciliter [dL] or per 100 milliliters [mL]) measures hemoglobin content in blood.

    • Hematocrit (Hct) measures red cell mass per 100 mL plasma volume and varies with extracellular fluid volume.

  • Laboratory Values:

    • RBC Count: 4.2-5.4 million/µL.

    • Reticulocytes: 1.0%-1.5% of total RBC.

    • Hemoglobin: 14-16.5 g/dL.

    • Hematocrit: 40-50%.

    • MCV: 85-100 fL (mean corpuscular volume).

    • MCHC: 31-35 g/dL (mean corpuscular hemoglobin concentration).

    • MCH: 27-34 pg/cell (mean cell hemoglobin).

vRed cell indices (MCV, MCHC, and MCH) are used to differentiate types of anemia according to size and color of red cells

§Mean corpuscle volume (MCV) ~ reflects the volume or size of the RBCs ~ MCV in ↓ microcytic (small cell) anemias and ↑ in macrocytic (large cell) anemias ~ some anemias are normocytic with normal size RBCs and MCV

§Mean corpuscular hemoglobin concentration (MCHC) ~ reflects the concentration of Hgb in each cell ~ anemias are described as normochromic (normal color) or hypochromic (↓ color)

§Mean cell hemoglobin (MCH) ~ refers to the mass of the RBC and is less useful in classifying anemias

vStained blood smears provide information on the size, color and shape of RBCs; and the presence of immature or abnormal cells

§If results are abnormal, a bone examination might be indicated

Blood Types and Transfusion Therapy

  • ABO Compatibility: Essential for safe and effective transfusion therapy.

    • Blood groups are genetically determined. ABO antibodies typically develop 3-6 months after birth, peaking at 5-10 years of age.

  • Major ABO Groups:

    1. Type A: A antigens present.

    2. Type B: B antigens present.

    3. Type AB: Both A and B antigens present.

    4. Type O: Neither A nor B antigens present.

  • Blood Group Antibodies:

    • Antibodies develop predictably in individuals whose RBCs lack the corresponding antigen:

    • Type A has B antibodies.

    • Type B has A antibodies.

    • Type AB has neither antibody.

    • Type O has both A and B antibodies.

    • All individuals can receive Type O blood, no one produces O antibodies

Rh System and Blood Compatibility

  • Rh Factor: D antigen is significant in transfusion compatibility.

    • Rh-positive indicates expression of the D-antigen.

    • Rh-negative indicates its absence.

    • Rh-positive individuals do not react adversely to Rh-negative blood; however, over 80% of Rh-negative individuals can become sensitized by Rh-positive blood.

Blood Transfusion Reaction

vThe most lethal blood transfusion reaction is the destruction of the donor red cells by reaction with antibodies in the recipient

§This immediate hemolytic reaction is usually 2° ABO incompatibility

§Potential clinical manifestations: hypotension, tachycardia, dyspnea, constricting chest pain, headache, chills, abdominal cramping, nausea, vomiting, sensation of heat along the transfusion line, facial flushing, urticaria, lumbar pain

oTransfusion needs to be immediately D/C