Chapter 15 - Blood

Blood: The River of Life

• Long before modern medicine, blood was seen as a mysterious life force.
• Severe bleeding leading to death reinforced the idea that life flowed out with blood.
• Blood was thought to determine personality and emotions.
• Examples:
  • "Bad blood" between feuding groups.
  • Anger causing blood to boil.
  • Fear generating "blood-curdling screams."
• Ethical and moral transgressions were believed to make blood "bad" or "impure," linking to diseases like syphilis and AIDS.
• Sharing blood could create a "blood brother."
• Today, while we don't use such terms, we recognize blood's importance for life and study it via hematology (hemat- meaning "blood").

Functions of Blood

• Blood flows in a closed system of vessels, propelled by the heart.
• Three Main Functions:
  • Transport:
    • Delivers oxygen ($O_2$) and nutrients to cells.
    • Removes waste from cells, delivering it to eliminating organs.
    • Transports hormones, ions, and other substances.
  • Regulation:
    • Maintains fluid and electrolyte balance.
    • Regulates acid-base balance.
    • Controls body temperature.
  • Protection:
    • Protects against infection with white blood cells.
    • Contains clotting factors to prevent excessive blood loss.

Composition of Blood

• Connective tissue with blood cells in a liquid intercellular matrix.
• Color varies from bright red (oxygenated) to darker blue-red (deoxygenated).
• Volume varies based on body size, gender, and age; averages 4-6 liters in adults.
• pH: Normal range is 7.35 to 7.45.
• Viscosity: Thickness of blood affecting flow ease.
  • Blood is 3-5 times more viscous than water.
  • Demonstrated by comparing water and molasses flow.

Two Parts of Blood

• Plasma:
  • Pale-yellow fluid, mostly water.
  • Contains proteins (albumin, clotting factors, antibodies, complement proteins), ions, nutrients, gases, and waste.
  • Plasma proteins regulate fluid volume, protect against pathogens, and prevent excessive blood loss.
  • Serum is plasma minus clotting proteins.
• Formed Elements (Blood Cells & Fragments):
  • Red Blood Cells (RBCs) / Erythrocytes: Transport $O_2$ to tissues.
  • White Blood Cells (WBCs) / Leukocytes: Protect against infection.
  • Platelets / Thrombocytes: Protect against bleeding.

Hematocrit

• Separation of blood in a centrifuge reveals blood cells at the bottom and plasma at the top.
• Hematocrit (Hct): Percentage of blood cells in a blood sample.
  • Normal: 45% blood cells (mostly RBCs), 55% plasma.
  • A small buffy coat layer between plasma and RBCs contains WBCs and platelets.
  • Changes in Hct usually reflect changes in RBC numbers.
  • Low Hct indicates anemia (lower than normal RBCs).
• Cautions: Hct is a percentage, so blood volume changes affect it.
  • Dehydration: Diminished blood volume falsely elevates Hct.
  • Overhydration (e.g., heart failure): Expanded blood volume falsely lowers Hct, causing "dilutional anemia."

Origin of Blood Cells (Hemopoiesis)

• Hemopoiesis: Process of blood cell formation.
• Occurs in hemopoietic tissue:
  • Red bone marrow: Myeloid hemopoiesis.
  • Lymphatic tissue: Lymphoid hemopoiesis (discussed in Chapter 21).
• Red bone marrow is found in ends of long bones (e.g., femur) and flat/irregular bones (e.g., sternum, cranial bones, vertebrae, pelvis).
• All three blood cell types (RBCs, WBCs, platelets) originate from the same stem cell in the red bone marrow.
• Stem cells differentiate into specific blood cells under the influence of growth factors.
  • Line 1: Stem cell -> RBC (erythrocyte).
  • Lines 2-4: Stem cells -> five types of WBCs (leukocytes); lymphocytes and monocytes originate in bone marrow, some lymphocytes mature/reproduce in lymphatic tissue.
  • Line 5: Stem cell -> megakaryocyte (large cell) -> platelets/thrombocytes (cell fragments).

Bone Marrow Disorders

• Myelosuppression (Bone Marrow Depression):
  • Bone marrow cannot produce enough blood cells.
  • Causes:
    • Aplastic anemia (RBC deficiency).
    • Leukopenia (WBC deficiency) leading to increased infection risk.
    • Thrombocytopenia (platelet deficiency) leading to bleeding/hemorrhage risk.
  • Causes of myelosuppression: cytotoxic cancer drugs, radiation, diseases.
  • Example: Madame Curie died of radiation-induced aplastic anemia.
• Polycythemia Vera (Bone Marrow Overactivity):
  • Excess production of blood cells, increasing blood thickness (viscosity).
  • Burdens the heart, overwhelms the clotting system.
  • Causes a beet-red, ruddy face due to increased RBC production.

Red Blood Cells (RBCs)

• Most numerous blood cells: 4.5-6.0 million per microliter (uL) of blood.
• Production rate: Millions per second in red bone marrow (erythropoiesis).
• Primary role: Transport of $O<em>2$ and carbon dioxide ($CO</em>2$).
• Stem cell differentiates into proerythroblast, then a mature erythrocyte (RBC).
• Reticulocyte: Immature RBC; develops into mature RBC within 48 hours of release into the blood.

Reticulocyte Count

• Normal range: 0.5% to 1.5% of RBCs.
• High reticulocyte count indicates:
  • Blood loss or iron deficiency stimulates bone marrow activity.
  • More severe blood loss leads to greater activity.
• Low reticulocyte count indicates:
  • Bone marrow is unable to make RBCs (e.g., myelosuppression).
• Changes in reticulocyte count provide diagnostic clues.

RBC Shape and Contents

• RBCs are large, flexible, disc-shaped cells with a thick outer rim and thin center.
• Because of size, RBCs stay in blood vessels, unlike WBCs.
• Flexibility allows squeezing through capillaries to deliver $O_2$ to cells.
• In sickle cell disease, RBCs assume a sickle shape, blocking blood flow and causing decreased oxygenation and cell death.
• Anisocytosis: Unequal-sized RBCs.
• Poikilocytosis: Irregularly shaped RBCs.
• Microcytic: Smaller than normal RBCs (e.g., iron deficiency anemia).
• Macrocytic: Larger than normal RBCs (e.g., vitamin $B_{12}$ deficiency anemia).
• Hypochromic: Pale RBCs.
• Normochromic: Normal color RBCs.
• Hyperchromic: Deeper red RBCs.
• Mature RBCs lack most organelles, including mitochondria and nucleus. Without mitochondria, RBC's produce adenosine triphosphate (ATP) anaerobically.
• RBCs do not use the $O_2$ they transport.
• Lacking DNA, RBCs cannot replicate and are replaced by new RBCs from bone marrow.

Hemoglobin

• Large protein molecule filling RBCs.
• Composed of:
  • Globin (protein).
  • Heme (iron-containing substance).
• Four globin chains per hemoglobin molecule, each with a heme group that binds to oxygen.
• Oxygenated hemoglobin: Oxyhemoglobin (bright red).
• Deoxygenated hemoglobin: Darker blue-red color.
• Globin transports some carbon dioxide ($CO_2$) from cells to lungs.
• $CO_2$-hemoglobin complex: Carbaminohemoglobin.

Blood Color Changes

• Oxygenated blood is bright red; deoxygenated blood is blue-red.
• Blood from lungs is oxygenated (red).
• Blood leaving tissues has given up $O_2$ (blue-red).
• Cyanosis: Bluish skin due to $O_2$ deficiency (hypoxemia).
• Cold temperatures cause vasoconstriction, slowing blood flow, increasing $O_2$ diffusion into tissues, leading to bluish color (cyanosis).
• Carbon monoxide (CO) poisoning:
  • Blood is bright cherry red.
  • CO binds to iron in hemoglobin, preventing $O_2$ transport, causing hypoxemia.
  • 20% of hemoglobin in smokers is unavailable for $O_2$ transport due to CO.

Hemoglobin Production

• Requires:
  • Correct genetic coding for protein synthesis.
  • Healthy bone marrow.
  • Raw materials: Iron, vitamin $B_{12}$, and folic acid.
• Deficiency in raw materials leads to specific types of anemia.
• Iron Deficiency Anemia:
  • Caused by inadequate iron intake.
  • More common in young women due to dieting, menstruation, and pregnancy.
  • Also common in low-income individuals due to expensive iron-rich foods.
  • Gastric bypass surgeries impair iron absorption.
• Iron combines with luminal to produce chemiluminescence (blue glow) for forensic blood detection.
• Deficiencies of folic acid and vitamin $B_{12}$ cause other specific anemias.

Regulation of RBC Production

• RBC count is maintained via negative feedback between blood $O_2$ levels and erythropoietin.
• Kidneys secrete erythropoietin (EPO) when tissue $O_2$ decreases.
• EPO stimulates bone marrow to produce more RBCs.
• Increased RBCs increase $O_2$ transport to tissues.
• Increased tissue $O_2$ diminishes EPO release, slowing RBC production.

Clinical Thoughts on EPO

• Chronic hypoxemia (e.g., emphysema) leads to excess EPO secretion, causing polycythemia (secondary polycythemia).
• High-altitude locations cause mild hypoxemia, stimulating EPO secretion and rising RBC count (secondary polycythemia).
• Athletes' use of EPO is illegal blood doping, increasing $O_2$ delivery to muscles.
• Declining kidney function reduces EPO production, causing anemia of chronic renal failure.

Removal and Breakdown of RBCs

• RBC lifespan: About 120 days.
• Mature RBCs lack a nucleus and must be replaced.
• Macrophages in spleen and liver detect and phagocytose ragged, misshapen RBCs.
• Recycling:
  • Hemoglobin is broken down into globin and heme.
    • Globin is broken into amino acids for protein synthesis.
    • Heme is broken into iron (stored in the liver) and bile pigments.
  • Liver removes bile pigments (especially bilirubin) and excretes them into bile, which is excreted in feces.
• Excessive RBC breakdown (hemolysis) leads to hyperbilirubinemia, causing jaundice (yellow skin).

White Blood Cells (WBCs)

• Large, round cells with nuclei, lacking hemoglobin.
• Fewer in number than RBCs.
• Protect the body by destroying pathogens and removing dead tissue via phagocytosis.
• Number generally increases during infection (leukocytosis), a few infections cause leukopenia.
• Lifespan varies: Granulocytes live hours, some lymphocytes live years.
• Normal range: 5,000 to 10,000 per microliter (uL), but they spend less than 12 hours in the blood.

Types of White Blood Cells

• Leukopoiesis: WBC production.
• Five types with different names, appearances, and functions (Table 15.2).
• Classified based on granules in their cytoplasm:
  • Granulocytes: Contain granules.
  • Agranulocytes: Lack granules.

Granulocytes

• Produced in red bone marrow.
• Classified by staining characteristics:
  • Neutrophils.
  • Basophils.
  • Eosinophils.

Neutrophils

• Most common granulocyte: 55-70% of total WBCs.
• Remain in blood for about 10-12 hours.
• Role: Phagocytosis and release of antimicrobial chemicals.
• Quickly move to the infection site to phagocytose pathogens and remove tissue debris.
• In the defense of the body, neutrophil's are important.
• Pus: Collection of dead neutrophils, cell parts, and fluid.
• Abscess: Walled-off collection of pus, preventing infection spread.
• Neutropenia/granulocytopenia (neutrophil deficiency) is life-threatening.
• Nicknames for mature and immature neutrophils:
  • Polymorphs/polymorphonuclear leukocytes (PMNs)/polys (many-shaped nucleus).
  • Segs (segmented nucleus of mature neutrophil).
  • Band cells/staff cells/stab cells (thick, curved band nucleus of immature neutrophil).

Shift to the Left

• Clinical phrase illustrating WBC response to a pathogen.
• Rapid production of neutrophils results in a greater proportion of immature neutrophils (bands).
• Shift to the left indicates infection.
• Term derived from early studies where cell types were listed with bands on the left.

Basophils

• Present in small numbers: less than 1% of WBCs.
• Absorb a dark blue stain.
• Role in the inflammatory response through histamine release.
• Release heparin (anticoagulant).
• Abundant in areas with large amounts of blood (e.g., lungs, liver).

Eosinophils

• Present in small numbers: 1-3% of WBCs.