Blood – Functions, Composition, and Immunohematology

Functions of Blood

• Transportation
  • Gases: \text{O}2 from lungs to tissues; \text{CO}2 from tissues to lungs
  • Nutrients: glucose, amino acids, lipids, iron, calcium, etc.
  • Hormones: endocrine distribution to target tissues
  • Metabolic wastes: urea, uric acid, bilirubin, etc. to excretory organs
• Regulation of pH & ionic composition of interstitial fluid
• Restriction of fluid loss at injury sites (hemostasis)
• Defense against toxins & pathogens (immune cells & antibodies)
• Stabilization of body temperature via heat absorption/redistribution

Composition of Blood

• Plasma (≈ 48\text{–}63\% of total volume)
  • Water (major constituent)
  • Proteins (albumin, globulins, fibrinogen, others)
  • Ions/electrolytes
  • Nutrients, hormones, wastes
• Formed Elements (≈ 37\text{–}52\% of total volume)
  • Erythrocytes (RBCs) – most abundant
  • Leukocytes (WBCs) – five major classes
  • Platelets (thrombocytes) – cell fragments
• Serum = plasma that has been allowed to clot (therefore lacks fibrinogen & clotting factors)

Plasma Proteins

• General rule: synthesized by liver except antibodies & some hormones
• Albumin (≈ 60\% of plasma proteins)
  • Major contributor to plasma colloid osmotic pressure
  • Transports fatty acids, thyroid hormone, some steroids, bilirubin, etc.
• Fibrinogen (≈ 4\%)
  • Inactive precursor → converted to fibrin during coagulation
  • Absent from serum
• Globulins
  • Gamma globulins = antibodies (immunoglobulins)
  • Other transport/functional proteins: antitrypsin, transferrin, macroglobulin, etc.
• “Other” proteins include circulating peptide/protein hormones

Red Blood Cells (Erythrocytes)

• Represent 99.9\% of formed elements
• Main function: transport \text{O}2; assist in \text{CO}2 transport (carbaminohemoglobin)
• Hematocrit (packed cell volume)
  • Normal females: 37\text{–}47\%
  • Normal males: 42\text{–}52\%
• Buffy coat (leukocytes + platelets) forms thin layer between plasma & RBCs in centrifuged blood

Structural Specializations

• Anucleate (no nucleus) → more intracellular space for hemoglobin
• No mitochondria → prevents consumption of transported \text{O}_2
• No ribosomes → cannot synthesize new proteins
• Biconcave disc
  • High surface-area-to-volume ratio enhances gas diffusion
  • Flexible membrane allows passage through narrow capillaries
• Cytoplasm ≈ \text{33}\% hemoglobin by volume

Hemoglobin (Hb)

• Quaternary protein: 4 polypeptide chains (2 α + 2 β)
• Each chain contains 1 heme group
  • Heme = porphyrin ring with central \text{Fe}^{2+} that reversibly binds 1 \text{O}_2 molecule
  • Thus 1 Hb can carry 4 \text{O}_2 molecules
• Affinity characteristics
  • High \text{O}_2 affinity in high-oxygen environments (lungs)
  • Low affinity when \text{O}_2 scarce (tissues) to facilitate release
• Fetal hemoglobin (HbF) has higher \text{O}_2 affinity than adult Hb (facilitates maternal–fetal transfer)
• Can transport small amount of \text{CO}_2 bound to globin (carbaminohemoglobin)

Lifecycle of RBCs (Erythropoiesis & Senescence)

• Erythropoiesis occurs in red bone marrow (sternum, ribs, vertebrae, pelvis, proximal limb bones in adults)
• Regulated by erythropoietin (EPO)
  • Kidneys detect tissue hypoxia → secrete EPO → stimulates marrow to increase RBC production
• Maturation sequence: stem cell → proerythroblast/erythroblast → reticulocyte → erythrocyte
  • Reticulocytes enter bloodstream; mature within ≈ 1\text{–}2 days
• Average circulating lifespan: \approx 120 days (≈ 700 miles traveled)
• Senescent/destructing RBCs
  • Removed by macrophages in spleen (major), liver, and bone marrow

Recycling & Fate of Hemoglobin Components

• Globin chains → hydrolyzed to amino acids → reused for protein synthesis
• Iron
  • Removed from heme; binds transferrin for transport in plasma
  • Stored in liver bound to ferritin or hemosiderin
  • Recycled into new heme in marrow
• Heme (without iron) → converted
  1. Heme → biliverdin (green)
  2. Biliverdin → bilirubin (yellow) → liver → bile → intestine → stercobilin (feces) & urobilin (urine)
• Excess/unusable heme or bilirubin accumulation manifests as jaundice

Disorders Related to RBCs

• Anemia = deficiency in RBC number and/or hemoglobin
  • Inadequate production
    • Iron deficiency (↓ Hb synthesis)
    • Folate/B12 deficiency (megaloblastic)
    • Thalassemia (globin gene mutations)
    • Leukemia or marrow failure/aplasia
    • Chronic kidney disease (↓ EPO)
  • Premature loss/destruction
    • Hemorrhagic anemia (bleeding)
    • Hemolytic anemia (RBC lysis) – autoimmune, malaria, toxins, sickle cell, etc.
• Polycythemia = excess RBC mass
  • Physiologic (living at high altitude, chronic hypoxia)
  • Iatrogenic (EPO doping)
  • Polycythemia vera (myeloproliferative disorder)

Recognizing RBC Disorders

• Clinical signs/symptoms of anemia: pallor, fatigue, dyspnea on exertion, tachycardia
• Laboratory assessment
  • Hematocrit (packed cell volume)
  • Hemoglobin concentration (g/dL)
  • RBC count, mean corpuscular volume (MCV), mean corpuscular Hb (MCH)
• Jaundice suggests bilirubin accumulation from hemolysis or hepatic dysfunction

Blood Antigens, Antibodies, & Agglutination

• Antigens: cell-surface molecules used by immune system for self vs. non-self recognition
• Antibodies (immunoglobulins): proteins produced by plasma cells targeting specific antigens
• Agglutination: cross-linking of antigens by antibodies causing visible clumping of cells/particles

ABO Blood Group System

• Determined by presence/absence of A & B antigens on RBC membrane
  • Type A: antigen A only
  • Type B: antigen B only
  • Type AB: both A & B antigens (rarest)
  • Type O: neither antigen (most common)

Plasma Antibodies (Agglutinins)

• Naturally occurring IgM antibodies against absent antigens
  • Type A → anti-B antibodies present; no anti-A
  • Type B → anti-A antibodies present; no anti-B
  • Type AB → none (no anti-A or anti-B) ⇒ “universal recipient” (for RBCs)
  • Type O → anti-A and anti-B present ⇒ “universal donor” (for RBCs)
• Each antibody can bind multiple antigens simultaneously → agglutination during mismatched transfusion

Transfusion Reactions

• Scenario: Type B recipient (has anti-A antibodies) receives type A blood
  • Anti-A antibodies bind donor A antigens → RBC agglutination → block microvasculature → hemolysis
  • Free hemoglobin may obstruct renal tubules → acute kidney failure → death if untreated

Donor & Recipient Compatibility Rules (ABO only)

• You can DONATE to individuals who possess all of your antigens
  • Type O → A, B, AB, O
  • Type A → A, AB
  • Type B → B, AB
  • Type AB → AB
• You can RECEIVE from donors whose antigens you already have (i.e., will not be viewed as foreign)
  • Type AB → A, B, AB, O (universal recipient)
  • Type A → A, O
  • Type B → B, O
  • Type O → O only

Rh (D) Blood Group System

• Rh (D) antigen discovered in rhesus monkeys (1940)
• Rh+ individuals possess D antigen; Rh− lack it
• Population prevalence in U.S.: \approx 85\% Rh+ ; \approx 15\% Rh−
• Anti-D antibodies are NOT naturally occurring; form only after exposure (sensitization)
  • Causes: transfusion with Rh+ blood, fetomaternal hemorrhage during pregnancy/birth
• Transfusion rules
  • Rh+ recipients: can receive Rh+ or Rh− blood (if ABO compatible)
  • Rh− recipients: must receive Rh− blood (ABO compatible) to avoid sensitization

Hemolytic Disease of the Newborn (HDN) / Erythroblastosis Fetalis

• Pathogenesis
  1. Rh− mother carries first Rh+ fetus → fetal RBCs enter maternal circulation (delivery, trauma) → mother forms anti-D IgG antibodies (sensitization)
  2. Subsequent Rh+ pregnancy → maternal IgG crosses placenta → binds fetal RBCs → hemolysis
• Clinical consequences: severe fetal anemia, jaundice, kernicterus (bilirubin-induced brain damage)
• Prevention
  • Administer Rho(D) immune globulin (RhoGAM) to Rh− mother at 28 weeks gestation & within 72 h postpartum/after any bleeding event
  • RhoGAM binds fetal Rh+ cells in maternal blood, preventing adaptive immune response & anti-D formation