Topic 04

Introduction to Blood

• Definition: Blood is a fluid used for internal transport.

Functions of Blood

• Transport

  • Delivers oxygen and nutrients to cells.

  • Carries carbon dioxide and waste to lungs and kidneys for elimination.

  • Transports hormones from endocrine organs to target organs.

• Regulation

  • Maintains body temperature and fluid volume.

  • Regulates blood pH using buffers (bicarbonate ions).

• Protection

  • Prevents blood loss through clot formation.

  • Carries immune agents (antibodies, white blood cells) to combat infection.

Composition of Blood

Overview

• Type: Only fluid tissue in the body; classified as connective tissue.

Components

• Plasma: Non-living fluid matrix.

• Formed Elements: Living cells including:

  • Erythrocytes (RBCs)

  • Leukocytes (WBCs)

  • Platelets

Physical Characteristics and Volume

• Hematocrit: percentage of erythrocytes (RBCs) in total blood volume

• Blood Volume: Approximately 8% of body weight.

• Normal Values:

  • Males: 47% ± 5%

  • Females: 42% ± 5%

• pH: Ranges from 7.35 to 7.45 (slightly alkaline).

• Avg Volume (Males 5-6L; Females 4-5L)

Plasma Composition

• Description: Straw-colored sticky fluid, about 90% water.

• Solutes: Over 100 including nutrients, electrolytes, and proteins.

• Albumin: Key carrier protein maintaining osmotic balance.

Formed Elements

Erythrocytes

Hematocrit: percentage of erythrocytes (RBCs) in total blood volume

• Shape: Biconcave; diameter of about 7.5 µm.

• Description:

  • Anuclear

  • No organelles

  • Can’t synthesize new proteins, grow, or divide

• Function: Oxygen transport.

• Structure: Lacks nuclei and organelles, filled with hemoglobin (97%).

  • Contains spectrin to maintain its shape

• Life span of 100-120 days

  • Old RBCs become fragile and Hb begins to degenerate

  • Macrophages in the spleen engulf and breakdown dying RBCs

  • Globin is metabolized into amino acids and released into circulation

  • Iron binds to ferritin or hemosiderin and is stored for reuse

  • Heme is degraded to bilirubin which is transformed into brown pigment stercobilin, leaves body in feces

Leukocytes

• Types include neutrophils, lymphocytes, monocytes, eosinophils, and basophils.

• Functions in immune response.

• Contain nuclei and organelles.

Platelets

• Definition: Cytoplasmic fragments from megakaryocytes, crucial for clotting.

• Lifespan: About 10 days.

Erythrocytes & Hemoglobin

• Hemoglobin Role: Binds oxygen, made of four heme groups that each bind to one O₂ (contains iron).

• Oxygen Loading/Unloading: Produces oxyhemoglobin (ruby red) in lungs and deoxyhemoglobin (dark red) in tissues.

• CO2 Transport: 20% binds to hemoglobin, forming carbaminohemoglobin.

Erythropoiesis (RBC Production)

• Definition: Formation of all blood cells that occur in red bone marrow from hematopoietic stem cells.

  • hematopoietic stem cells, also known as hemocytoblasts give rise to all formed elements

• Stages take approximately 15 days to complete.

Regulation of Erythropoiesis

Homeostatic Mechanisms

• Balance: Too few RBCs lead to hypoxia; too many increase viscosity.

  • Balance is determined by diet and hormones

• Hormonal Control: Erythropoietin (EPO) stimulates RBC formation in response to low oxygen levels.

  • Hypoxia-inducible factor (HIF), builds up in hypoxia

    • HIF increases synthesis of EPO

  • EPO can be used by athletes as a performance enhancer

    • Tricks the body into producing more red blood cells

• Normoxia: normal RBC levels

• Causes of hypoxia:

  • Decreased RBC numbers due to hemorrhage, blood loss, or increased RBC destruction

  • Insufficient hemoglobin per RBC (example: iron deficiency)

  • Reduced availability of O2 (example: high altitudes or lung problems such as pneumonia)

Dietary Requirements

• Essential for cell synthesis are amino acids, lipids, carbs

• Essential DNA synthesis are vitamin B12 and folic acid.

• Others: iron

Erythrocyte Disorders

Anemia

• Definition: blood carries abnormally low O₂

• Symptoms: fatigue, pallor, shortness of breath, chills

• Three types of anemia

  • Blood loss

  • Not enough RBCs produced

  • Too many RBCs being destroyed

Types of Anemia

• Iron-deficiency anemia: Characterized by small, pale RBCs.

  • low iron intake or impaired absorption

  • RBCs produced are called microcytes

    • Small, pale in colour

    • Cannot synthesize hemoglobin because there is a lack of iron

• Pernicious anemia: Results from lack of intrinsic factor and vitamin B12, leading to enlarged RBCs.

  • intrinsic factors need to absorb vitamin B₁₂

  • Autoimmune disease that destroys stomach mucosa that produces intrinsic factor needed to absorb Vitamin B₁₂

  • Without B₁₂, RBCs enlarge but cannot divide, resulting in large macrocytes

  • Can also be caused by low dietary intake of B₁₂

• Hemolytic anemia: Premature destruction of RBCs.

  • Caused by

    • incompatible transfusions

    • hemoglobin abnormalities

  • Thalassemias

    • faulty globin chain

    • common in people of Mediterranean ancestry

  • Sickle cell anemia

    • mutated hemoglobin

    • one amino acid residue is altered

    • RBCs are crescent shaped when C levels are low

    • Misshaped RBCs rupture easily and block small vessels

      • Results in poor O₂ delivery and pain

    • Benefits

      • resistant to malaria

      • heterozygous have better chance of surviving malaria

    • homozygous can develop sickle cell anemia

Polycythemia

• Definition: Abnormal excess of RBCs, increasing blood viscosity.

• Types:

  • Polycythemia vera

    • bone marrow cancer leading to excess RBCs

    • hematocrit may go as high as 80%

    • treatment: therapeutic phlebotomy

  • secondary polycythemia (due to low oxygen levels).

    • increased EPO productions

    • examples: high altitude

Platelet

• cytoplasmic fragments of megakaryocytes

  • Stage IV megakaryocyte: Projections break off into anuclear platelet fragments

• formation regulated by thrombopoietin

• formed in the myeloid line

• degenerate in about 10 days

• Granules contain factors that act in clotting process

• Normal = 150 000 – 400 000 platelets/ml of blood

Platelet Function and Hemostasis

• Hemostasis: Series of reactions to stop bleeding (involves vascular spasm, platelet plug, coagulation).

• Function: form temporary platelet plug that helps seal breaks in blood vessels

• Platelet Characteristics: Contain factors for clotting and are kept inactive and mobile by nitric oxide & prostacyclin from the endothelial cells lining blood vessels until needed.

Clotting Process

Phases

1. Vascular Spasm: immediate vasoconstriction responds to injury.

   • most effective in smaller vessels

   • significantly reduces blood flow

2. Platelet Plug Formation - platelets adhere to damaged areas and activate.

   • only sticks to collagen fibers that are exposed when vessel is damaged

   • von Willebrand factor helps stabilize platelet-collagen adhesion

   • Platelets swell, become spiked and sticky, releasing chemical messengers

     • ADP causes more platelets to stick

     • Serotonin and thromboxane A2 enhance vascular constriction and platelet aggregation

     • positive feedback loop

   • plugs are small enough for small vessel tears

3. Coagulation (Blood Clotting) - reinforces plug with fibrin.

   • good at sealing larger breaks in blood vessel

   • blood is turned into gel

   • Series of reactions use clotting factors (procoagulants), mostly plasma proteins

Coagulation Pathways

• Intrinsic Pathway: Triggered by blood components.

  • phase one produces prothrombin activator

  • phase two converts prothrombin into thrombin

    • pro (beginning), or (ogen) = inactive precursor meant to be converted

  • phase three takes thrombin to convert fibrinogen into insoluble fibrin

    • causes plasma to become gel-like trap to catch formed elements

  • slower than extrinsic pathway

• Extrinsic Pathway: Initiated by tissue factor (TF).

  • phase one produces prothrombin activator

  • phase two converts prothrombin into thrombin

    • pro (beginning), or (ogen) = inactive precursor meant to be converted

  • phase three take thrombin to convert fibrinogen into insoluble fibrin

    • causes plasma to become gel-like trap to catch formed elements

  • faster than intrinsic pathway

Clot Retraction and Fibrinolysis

• Clot must be stabilized and removed when damage has been repaired

• Clot retraction:

  • contractile proteins (acitin & myosin) contract withing 30-60 minutes

  • Contraction pulls on fibrin strands, squeezing serum from clot

    • serum is plasma minu clotting proteins

    • compacts clot, helping to seal the wound

  • draws ruptured blood vessel edges together

• Vessel heals during clot retraction

• Platelet-derived growth factor (PDGF) is released by platelets

  • Stimulates division of smooth muscle cells and fibroblasts to rebuild blood vessel wall Platelet-derived growth factor

• Fibrinolysis

  • process where clots are removed after repair is completed

  • begins withing 2 days and continues until clot is dissolved

  • Plasminogen, lasma protein that is trapped in clot, is converted to plasmin (a fibrin-digesting enzyme)

    • Tissue plasminogen activator (tPA), factor XII, and thrombin all play a role in conversion process
      

Factors Limiting Clot Growth

• Mechanisms:

  • Rapid removal of clotting factors

  • Inhibition of activated factors

    • limited amount of thrombin is restricted to clot by fibrin threads

    • Antithrombin III inactivates any unbound thrombin that escapes into bloodstream

Disorders of Hemostasis

Thromboembolic Conditions

• Thrombus

  • clot that develops and persists in unbroken blood vessel

• Embolus

  • free floating thrombus

• Embolism

  • embolus obstructing a vessel, too small to continue to pass through
    

• Risk Factors: Include atherosclerosis, inflammation, and blood stagnation.

Anticoagulant Drugs

• Uses: prevention of undesirable clotting

• Types:

  • Aspirin - inhibits thromboxane A2 (blocking platelet aggregation and platelet plug formation)

  • Heparin - used clinically for pre-and postoperative cardiac care

  • Warfarin - used for people prone to atrial fibrillation & interferes with the action of vitamin K

Leukocytes Overview

• Approx. 4,800 to 10,800 WBCs per µl; function primarily in immune defense.

• Types: Granulocytes and agranulocytes.

• Functions:

  • defence against diseases

  • leaves capillaries via dia[edisis

  • move through tissue spaces by amoeboid

Granulocytes

• Include neutrophils (50-70%), eosinophils (2-4%), and basophils(0.5-1%), each with unique functions in immune response.

• Larger and less lifespans than RBCs

• contained lobed nuclei

• All are phagocytic

• Neutrophils

  • Granules stain with both acid (red) and basic (blue) dyes

  • make up 50-70% of WBC’s

  • about twice the size of WBCs

  • Granules contain either hydrolytic enzymes or antimicrobial Proteins

  • Kills microbes via respiratory burst

    • very phagocytic

    • referred to as bacteria slayers

  • Defensin granules merge with phagosome

    • Form “spears” that pierce holes in membrane of ingested microbe

• Eosinophils

  • 2–4% of all leukocytes

  • Nucleus has two lobes

  • Red-staining granules contain digestive enzymes

• Basophils

  • 0.5–1% of leukocytes (rarest WBC)

  • Nucleus deep purple with one to two constrictions

  • Large, purplish black (basophilic) granules contain histamine

    • Histamine: inflammatory chemical that acts as vasodilator

      and attracts WBCs to inflamed sites

  • functionally similar to mast cells

Agranulocytes

• Comprised of lymphocytes and monocytes, crucial for adaptive immunity.

• Lymphocytes

  • Second most numerous WBC, accounts for 25%

  • Mostly found in lymphoid tissue (example: lymph nodes, spleen)

  • Two types

    • T lymphocytes (T cells) act against virus-infected cells and

      tumour cells

    • B lymphocytes (B cells) give rise to plasma cells, which

      produce antibodies

• Monocytes

  • Largest leukocytes; 3-8% of all WBCs

  • U- or kidney-shaped nuclei

  • Leave circulation, enter tissues, and differentiate into macrophage

  • Activate lymphocytes to mount an immune response

Production and Life Span of Leukocytes

• Leukopoiesis: production of WBCs

• Leukocytes originate from hematopoietic stem cell that branches into two pathways:

  • Lymphoid stem cells - produces lymphocytes

  • Myeloid stem cells - produce all other formed elements

Leukocyte Disorders

• Leukemia

  • Cancerous condition involving overproduction of abnormal WBCs

  • Usually involve clones of single abnormal cell

  • Acute (quickly advancing)

    • primarily affect kids

  • Chronic (slowly advancing)

    • primarily affects adults

• Leukopenia

  • Abnormally low WBC count

  • Often induced by drugs (ie glucocorticoids and anticancer agents)

Overview

• Leukopenia: Low WBC count, often drug-induced.

• Leukemia: Overproduction of abnormal WBCs, can be acute or chronic, affecting various age groups, with serious health implications.