MR

Comprehensive Notes — Chapter 17: Blood

Blood as a Connective Tissue

  • Embryological origin: arises from mesoderm-derived mesenchymal cells → classifies blood as a connective tissue even though it normally neither binds nor supports.
  • Dual phase:
    • Plasma (aqueous, ~90 % H₂O)
    • Formed elements (cells + cell fragments).

Normal Physical Parameters

  • pH: normal set point 7.4; acceptable range 7.35\text{–}7.45.
    • Deviations trigger respiratory compensation (hyper- or hypoventilation).
  • Temperature: blood ≈ 38^\circ\text{C} (≈1 °C warmer than core body temperature 37^\circ\text{C}).
  • Fraction of body mass: ≈8 %.
  • Typical volumes:
    • Male 5\text{–}6\,\text{L}
    • Female 4\text{–}5\,\text{L} (difference largely size-related).

Hematocrit

  • Definition: % of whole-blood volume occupied by erythrocytes.
  • Normal values:
    • Males 44\text{–}46\% (≈45 %)
    • Females 42\text{–}44\% (≈43 %).
  • ↑Hematocrit → ↑viscosity → ↑cardiac work.

Functional Roles of Blood

  • Distribution/transport: O₂, CO₂, nutrients, hormones, heat.
  • Regulation: body temperature, pH buffering, blood volume ↔ blood pressure (RAAS, aldosterone, ACE inhibitors).
  • Protection:
    • Hemostasis (platelets + fibrinogen).
    • Immune defense (leukocytes).

Plasma: Composition & Functions

  • ~90 % water; 10 % "solids" (solutes).
  • Major plasma proteins (produced by liver):
    • Albumin: osmotic pressure maintenance, transport carrier.
    • Globulins: transport & immune functions.
    • Fibrinogen → fibrin during clotting.
  • Other solutes: electrolytes (Na⁺, K⁺), glucose, amino acids, vitamins, minerals, fatty acids/lipids, hormones, dissolved gases (mainly CO₂, N₂).

Formed Elements: Overview

  • Erythrocytes (RBCs): majority; anucleate biconcave discs; no mitochondria; anaerobic glycolysis.
  • Leukocytes (WBCs): <1 % of blood; true nuclei; immune roles.
  • Platelets (thrombocytes): cell fragments from megakaryocytes; hemostasis.

Erythrocytes in Detail

  • Shape: biconcave → high surface area/volume; squeezes through capillaries.
  • Cytoskeletal protein spectrin adds flexibility & durability (≈1,440 capillary passages/day).
  • 97 % of intracellular volume = hemoglobin.
  • ATP derived via anaerobic glycolysis (no mitochondria → RBCs do not consume transported O₂).

Hemoglobin (Hb)

  • Quaternary protein: 4 globin chains (α₁, α₂, β₁, β₂) each with a heme.
  • Each heme contains Fe²⁺ center binding 1 O₂ → 1 Hb carries 4 O₂.
  • States:
    • Oxyhemoglobin (HbO₂): O₂-bound, "open" conformation.
    • Deoxyhemoglobin (HHb): O₂-released, "closed".
    • Carbaminohemoglobin: ≈20 % of CO₂ binds reversibly to globin.
    • Carbon-monoxyhemoglobin: CO binds irreversibly → poisoning.
  • RBC payload: ≈2.5\times10^{8} Hb molecules/cell → ≈10^{9} O₂ molecules per RBC.

Hemoglobin Concentrations

  • Children (pre-puberty): 14\text{–}20\,\text{g dL}^{-1}.
  • Adult males: 13\text{–}18\,\text{g dL}^{-1} (avg 14–15).
  • Adult females: 12\text{–}16\,\text{g dL}^{-1} (avg 13–14).

Regulation of Erythropoiesis

  • Sensor: kidneys monitor blood O₂ content (receive ≈20 % CO).
  • Low O₂ (hemorrhage, altitude, COPD, donation) → kidneys secrete erythropoietin (EPO).
  • EPO stimulates red bone marrow → ↑erythrocyte production → ↑Hb & ↑O₂ capacity.
  • Negative feedback: restored O₂ → ↓EPO secretion.

Polycythemia & Blood Doping

  • Polycythemia vera: marrow tumor → excessive RBCs → hyper-viscosity; treated by phlebotomy.
  • Physiologic polycythemia: altitude exposure (“live high-train low”).
  • Autologous transfusion (freeze–thaw RBCs) & recombinant EPO injections = illicit "blood doping" → performance ↑ but detectable (reticulocytes, hemolysis → jaundice).

Lifespan & Fate of RBCs

  • Longevity: 100\text{–}120\,\text{days}.
  • Clearance: macrophages (liver > spleen > marrow) phagocytose aged/damaged RBCs.
  • Recycle pathways:
    • Globin → amino acids.
    • Heme → Fe²⁺ (stored as ferritin/hemosiderin) + bilirubin (→ bile in gallbladder → intestinal fat absorption).

Anemias

  1. ↓ RBC number
    • Hemorrhagic (acute/chronic blood loss).
    • Hemolytic (rupture: transfusion errors, infections, frozen-cell doping).
    • Aplastic (marrow destruction—radiation, chemotherapy).
  2. ↓ or abnormal Hb
    • Iron-deficiency (diet, pregnancy) → microcytic hypochromic cells.
    • Athlete’s “pseudo-anemia”: plasma expansion dilutes Hb (non-pathological).
    • Pernicious (vit-B₁₂ deficiency; intrinsic-factor or vegan diet).
    • Genetic Hb defects:
    – Thalassemia (Mediterranean; absent globin chains).
    – Sickle-cell (Central Africa; β-globin point mutation → HbS polymerization after O₂ unload → sickling, pain, vessel blockage).
    – Both mutations confer partial malaria resistance (heterozygote advantage).

Leukocytes (WBCs)

  • Overall count: ≈4\text{–}11\times10^{3}\,\text{μL}^{-1}; <1 % blood volume.
  • Categories:
    • Granulocytes: neutrophils (50–70 %; first responders, phagocytic), eosinophils, basophils.
    • Agranulocytes: lymphocytes (T, B, NK—adaptive immunity, antibodies), monocytes (→ macrophages in tissues).

Leukocyte Disorders

  • Leukemia: malignant proliferation of non-functional WBCs → anemia, infections, ↑viscosity; treated with irradiation & marrow transplant.
  • Infectious mononucleosis: Epstein–Barr virus targets agranulocytes; self-limiting.

Platelets & Hemostasis

  • Origin: cytoplasmic fragments of megakaryocytes; 2–4 µm; contain granules (serotonin, ADP, thromboxane A₂).
  • Normal count ≈1.5\text{–}4\times10^{5}\,\text{μL}^{-1}.
  • Hemostatic sequence:
  1. Vascular spasm.
  2. Platelet plug formation: injured endothelium exposes collagen → platelets adhere, degranulate, become sticky, recruit more platelets.
  3. Coagulation cascade: platelet & tissue factors convert soluble fibrinogen → insoluble fibrin mesh; reinforces plug (common pathway: prothrombin → thrombin → fibrinogen → fibrin).

Blood Clot Visualization

  • Fibrin strands + trapped RBCs produce red “scab” seen externally; internally halts hemorrhage until vessel repair.

ABO Blood Typing

  • Surface antigens on RBC membrane:
    • Type A → A antigen, anti-B antibodies.
    • Type B → B antigen, anti-A antibodies.
    • Type AB → A + B antigens, no antibodies (universal recipient).
    • Type O → no A/B antigens, anti-A & anti-B antibodies (universal donor).
  • Transfusion rule: avoid giving donor RBC antigens that recipient plasma contains antibodies against.

Agglutination Test Procedure

  • Two drops of patient blood.
  • Add anti-A serum to one, anti-B serum to other.
  • Agglutination (clumping) = presence of corresponding antigen.
  • Interpretation examples:
    • Clumps with both → Type AB.
    • Clumps only with anti-B → Type B.
    • Clumps only with anti-A → Type A.
    • No clumping → Type O.

Rh (Rhesus) Factor

  • Major antigen = D.
  • Rh⁺: D antigen present (≈85 % U.S.).
  • Rh⁻: D antigen absent; no pre-existing anti-D antibodies—must be sensitized.
  • Clinical importance:
    • First mismatched transfusion to Rh⁻ person → sensitization, mild reaction.
    • Subsequent exposure → severe hemolysis.

Hemolytic Disease of the Newborn (Erythroblastosis fetalis)

  • Rh⁻ mother × Rh⁺ father → Rh⁺ fetus.
  • During first delivery maternal blood exposed to D antigen → anti-D antibody production.
  • Future Rh⁺ pregnancies → maternal IgG crosses placenta, destroys fetal RBCs.
  • Prevention: RhoGAM (anti-D Ig) given to Rh⁻ mothers during/after first pregnancy → binds fetal D antigen before maternal immune activation.

Key Numbers & Facts to Memorize

  • pH range: 7.35\text{–}7.45; temperature 38^\circ\text{C}.
  • Blood volumes: M 5\text{–}6\,\text{L}; F 4\text{–}5\,\text{L}.
  • Hematocrit: M ≈45\%; F ≈43\%.
  • Hb/cell: \approx2.5\times10^{8} → ≈10^{9} O₂ molecules per RBC.
  • Lifespan of RBC: 100\text{–}120 days.
  • Circulatory loops/day per RBC at rest: 1440.
  • Plasma water: ≈90 %.
  • Platelet count: 150\text{–}400\,\times10^{3}\,\mu\text{L}^{-1}.

Concept Connections & Clinical Relevance

  • Acid–base homeostasis ↔ respiration & renal regulation.
  • RAAS pharmacology (ACE inhibitors) depends on plasma volume control.
  • Hb structure parallels myoglobin & links to respiratory physiology.
  • Spectrin mutations → hereditary spherocytosis (example of membrane-cytoskeleton importance).
  • Blood doping ethics: performance vs health risks (polycythemia, heart failure).
  • Neonatal jaundice & bilirubin metabolism tie into RBC turnover pathway.
  • Iron metabolism disorders (hemochromatosis) relate to ferritin storage step.
  • Leukemia illustrates uncontrolled mitosis vs normal post-mitotic status of mature blood elements.
  • RhoGAM prophylaxis showcases adaptive immunity specificity and maternal-fetal medicine.