Comprehensive Study Notes on Blood: Anatomy and Physiology

Characteristics and Functions of Blood

• Definition and Tissue Type: Blood is the only connective tissue that exists in a liquid state. The liquid portion is known as plasma.

• Primary Functions:

  • Transport: Moves oxygen ($O_{2}$), nutrients, hormones, and waste products throughout the body.

  • Regulation: Maintains homeostasis by regulating body processes such as pH levels and fluid balance.

  • Stabilization: Maintains the stability of interstitial fluid (the fluid surrounding cells).

  • Heat Distribution: Distributes heat generated by metabolic processes throughout the body.

• Blood Volume Factors: Total blood volume depends on three primary variables:

  1. Body size.

  2. Fluid and electrolyte levels.

  3. Amount of adipose (fat) tissue.

• Blood Volume Statistics:

  • Blood accounts for approximately $8\%$ of total body weight.

  • Average Adult Female: $4$ to $5\,\text{liters}$.

  • Average Adult Male: $5$ to $6\,\text{liters}$.

Blood Composition

• Plasma ($55\%$ of blood volume):

  • Water: Approximately $92\%$.

  • Proteins: Approximately $7\%$. Includes Albumins ($60\%$), Globulins ($36\%$), and Fibrinogen ($4\%$).

  • Other Solutes: Electrolytes, wastes, nutrients, gases ($N_{2}$, $O_{2}$, $CO_{2}$), vitamins, and hormones.

• Formed Elements ($45\%$ of blood volume):

  • Red Blood Cells (Erythrocytes): Comprise $95.1\%$ of the formed elements.

  • Platelets (Thrombocytes): Comprise $4.8\%$ of the formed elements.

  • White Blood Cells (Leukocytes): Comprise $0.1\%$ of the formed elements. Types include:

    • Neutrophils: $50\text{--}70\%$ of WBCs.

    • Lymphocytes: $25\text{--}33\%$ of WBCs.

    • Monocytes: $3\text{--}9\%$ of WBCs.

    • Eosinophils: $1\text{--}3\%$ of WBCs.

    • Basophils: Less than $1\%$ of WBCs.

Centrifugation and the Hematocrit

• Centrifugation Process: Blood draws are centrifuged to detect abnormalities. Components separate by density:

  • Plasma: Found at the top of the tube; a clear, straw-colored fluid matrix representing about $55\%$ of blood volume.

  • Buffy Coat: A thin middle layer containing white blood cells and platelets; makes up less than $1\%$ of blood volume.

  • Red Blood Cells: Found at the bottom of the tube.

• Hematocrit (HCT): The specific percentage of red blood cells in a sample.

  • Females: Normal range is $35$ to $46\%$.

  • Males: Normal range is $40$ to $54\%$.

Red Blood Cells (Erythrocytes)

• Function: Specialized for carrying oxygen from the lungs to tissues and removing carbon dioxide.

• Structure:

  • Biconcave Disc: This shape increases the surface area available for gas exchange.

  • Flexibility: Allows cells to squeeze through narrow capillaries.

• Cellular Contents:

  • Hemoglobin: Occupies about $1/3$ of the cell's volume.

    • Oxyhemoglobin: Hemoglobin bound to oxygen; appears bright red.

    • Deoxyhemoglobin: Hemoglobin without oxygen; appears darker, bluish-red.

  • Lack of Organelles: Mature RBCs have no nucleus (cannot divide or synthesize proteins) and no mitochondria (utilize glycolysis so they do not consume the oxygen they transport).

• Red Blood Cell Counts (RBCC or RCC):

  • Defined as the number of RBCs in a cubic millimeter or microliter ($\mu\text{L}$) of blood.

  • Typical Ranges:

    • Male: $4,700,000$ to $6,100,000$ per $\mu\text{L}$.

    • Female: $4,200,000$ to $5,400,000$ per $\mu\text{L}$.

  • Counts are used to diagnose diseases and evaluate oxygen-carrying capacity.

Erythropoiesis: RBC Production and Control

• Location: Occurs in red bone marrow.

• Regulatory Mechanism (Negative Feedback Loop):

  1. Trigger: Low blood oxygen levels.

  2. Organ Response: The kidneys and liver release the hormone erythropoietin (EPO).

  3. Action: EPO signals red bone marrow to increase RBC production.

  4. Result: Increased RBCs improve oxygen levels, which leads to a decrease in EPO release.

• Stages of Development:

  1. Hemocytoblast: The multipotent stem cell.

  2. Erythroblast: Stage where hemoglobin production begins.

  3. Reticulocyte: An immature RBC that enters the bloodstream.

  4. Erythrocyte: The mature red blood cell.

• Lifespan: Approximately $120\,\text{days}$. During its life, a single RBC may travel through the body $75,000\,\text{times}$.

RBC Destruction and Recycling

• Filtration: Old or damaged RBCs are removed by the spleen and liver.

• Macrophages: These immune cells phagocytize ("eat") the RBCs.

• Hemoglobin Breakdown:

  • Globin Chains: The protein portion is broken down into amino acids to be reused by the body.

  • Heme Groups: Broken down into two components:

    • Iron (Fe): Recycled and bound to the transport protein transferrin. It is sent back to red bone marrow for new hemoglobin production.

    • Biliverdin: A green pigment that is subsequently converted into bilirubin (a yellowish pigment).

• Excretion: Pigments are excreted into bile, enter the small intestine, and leave the body in feces or are carried to the kidneys to be eliminated in urine.

White Blood Cells (Leukocytes)

• Main Function: Protect the body against disease.

• Production: Produced in red bone marrow under the control of interleukins and colony-stimulating factors (CSFs).

• Type 1: Granulocytes (Visible granules, short lifespans):

  • Neutrophils: Most abundant ($50\text{--}70\%$); contain a multilobed nucleus; act as first responders to phagocytize bacteria, viruses, and debris.

  • Eosinophils: ($1\text{--}3\%$ or up to $4\%$); have a bilobed nucleus and bright red granules; fight parasitic infections and regulate allergic reactions.

  • Basophils: (Less than $1\%$); have large blue granules; release histamine (promotes inflammation) and heparin (inhibits blood clotting).

• Type 2: Agranulocytes (No noticeable granules):

  • Monocytes: Largest WBCs ($3\text{--}9\%$); can live for weeks or months; leave the blood to become macrophages that phagocytize large particles.

  • Lymphocytes: Smallest WBCs ($25\text{--}33\%$); contain a large spherical nucleus; may live for years.

    • T cells: Directly attack pathogens and tumor cells.

    • B cells: Produce antibodies for immunity.

White Blood Cell Functions and Behaviors

• Diapedesis: The ability of WBCs to squeeze between cells of capillary walls to leave the vessel and reach infection sites.

• Cellular Adhesion Molecules (CAMs): Proteins that direct WBCs to injury sites.

• Positive Chemotaxis: The process where WBCs are attracted to infection sites by chemicals released from damaged cells.

• Inflammatory Response: Promoted by basophils; involves swelling and increased capillary permeability to restrict the spread of infection.

• Bacterial Invasion Sequence:

  1. Injury (e.g., splinter) introduces bacteria into the dermis.

  2. Bacteria multiply; injured cells release histamine.

  3. Blood vessels dilate and become leaky.

  4. Neutrophils move through vessel walls (diapedesis).

  5. Neutrophils destroy bacteria via phagocytosis.

WBC Counts and Disorders

• Standard Count: Typically ranges from $3,500$ to $10,500$ per $\mu\text{L}$.

• Leukocytosis: WBC count above $10,500\,\mu\text{L}^{-1}$. Indicates acute infection, vigorous exercise, or significant fluid loss.

• Leukopenia: WBC count below $3,500\,\mu\text{L}^{-1}$. Found in conditions like typhoid fever, influenza, measles, mumps, AIDS, and certain anemias.

• Differential WBC Count: Lists the percentages of each WBC type. Useful for diagnosis:

  • Bacterial Infection: Neutrophil percentage increases.

  • HIV Infection: Helper T-cell count (a lymphocyte) decreases.

• Leukemia: A cancer of the white blood cells.

  • Acute: Sudden onset and rapid progression.

  • Chronic: Slower onset, may go undetected for years.

  • Lymphoid: Cancer of lymphocytes in lymph nodes.

  • Myeloid: Cancer of granulocytes in red bone marrow.

  • Symptoms: High WBC count, fatigue, nosebleeds, bone pain, fever, and bruising due to increased clotting time.

Platelets (Thrombocytes)

• Origin: Cytoplasmic fragments of megakaryocytes found in red bone marrow.

• Structure: Very small (less than half the size of an RBC), lacking a nucleus.

• Count: Normal range is $150,000$ to $400,000$ per $\mu\text{L}$.

• Disorders:

  • Thrombocytosis: Count too high (often due to infection/iron deficiency); increases risk of abnormal clots.

  • Thrombocytopenia: Count too low (often due to cancer treatments); leads to easy bruising and bleeding.

• Functions:

  • Hemostasis: Stick to broken surfaces to stop bleeding.

  • Serotonin Release: Causes smooth muscle contraction in vessel walls to reduce blood flow.

Plasma Solutes and Proteins

• Plasma Composition: $92\%$ water, serves as a transport medium.

• Plasma Proteins:

  • Albumins ($60\%$): Produced in the liver; maintain colloid osmotic pressure.

  • Globulins ($36\%$):

    • Alpha and Beta: Produced in the liver; transport lipids and fat-soluble vitamins.

    • Gamma: Produced in lymphatic tissues; act as antibodies.

  • Fibrinogen ($4\%$): Produced in the liver; essential for blood coagulation.

• Blood Gases: Oxygen (for cellular function) and Carbon Dioxide (waste product).

• Nutrients: Amino acids, simple sugars (glucose), nucleotides, and lipids.

  • Lipid Types: Triglycerides (energy), Phospholipids (membranes), and Cholesterol (hormone precursor/membrane flexibility).

• Electrolytes: Ions that conduct electricity and regulate hydration, heart rhythm, and blood pressure.

  • Includes: Sodium ($Na^{+}$), Potassium ($K^{+}$), Calcium ($Ca^{2+}$), Magnesium ($Mg^{2+}$), Chloride ($Cl^{-}$), Bicarbonate ($HCO_{3}^{-}$), Phosphate ($PO_{4}^{3-}$), and Sulfate ($SO_{4}^{2-}$).

  • $Na^{+}$ and $Cl^{-}$ are the most abundant.

Hemostasis: Mechanics of Blood Stoppage

1. Blood Vessel Spasm: Immediate contraction of the vessel wall to restrict blood flow.

2. Platelet Plug Formation: Platelets adhere to broken vessel edges and each other to create a temporary plug.

3. Blood Coagulation (Clotting): Formation of a strong fibrin net. Fibrinogen is converted into fibrin, which traps cells to seal the breach.

The Fate of Blood Clots

• Clot Retraction: The clot shrinks, pulling vessel edges together and squeezing out serum (plasma without clotting proteins like fibrinogen).

• Repair: Platelets release platelet-derived growth factor (PDGF) to stimulate smooth muscle and fibroblast activity for vessel repair.

• Fibrinolysis: The enzyme plasmin breaks down the fibrin net once healing is sufficiently underway, dissolving the clot.

Abnormal Blood Clotting and Disorders

• Thrombus: An abnormal clot forming in a vessel.

• Embolus: A clot that has broken free and is moving through the bloodstream.

• Thrombosis: A clot blocking a vessel in a vital organ.

• Infarction: Death of tissue caused by a blocked vessel.

• Embolism: An embolus that becomes lodged and blocks a vessel (e.g., pulmonary embolism).

• Atherosclerosis: Accumulation of fat in arterial linings that can trigger thrombosis.

• Inherited Disorders:

  • Factor V Leiden: Increased risk of deep vein thrombosis.

  • Hemophilia: Bleeding caused by a lack of specific clotting factors.

  • Sickle Cell Disease: Abnormal hemoglobin crystallizes in low oxygen, causing RBCs to sickle and block circulation.

  • Von Willebrand Disease: Lack of von Willebrand factor causes bleeding (less severe than hemophilia).

  • Hereditary Hemochromatosis: Excess absorption and deposition of iron.

Blood Groups and Transfusions

• Antigens: Molecules on the surface of RBCs that evoke immune responses.

• Antibodies: Proteins in plasma that react against specific foreign antigens.

• Agglutination: Clumping of RBCs when antibodies encounter their specific target antigen. This causes a transfusion reaction (headache, facial flushing, pain, jaundice, breathing issues).

• ABO Blood Group:

  • Type A: Antigen A; Antibody Anti-B. Receives from A, O.

  • Type B: Antigen B; Antibody Anti-A. Receives from B, O.

  • Type AB: Antigens A and B; No antibodies. Universal Recipient. Receives from A, B, AB, O.

  • Type O: Neither Antigen A nor B; Both Anti-A and Anti-B antibodies. Universal Donor. Receives only from O.

Rh Blood Group

• Antigen D: The most important Rh antigen. If present, the person is Rh-positive ($Rh^{+}$); if absent, they are Rh-negative ($Rh^{-}$).

• Anti-Rh Antibody Formation: $Rh^{-}$ individuals do not naturally have Anti-Rh antibodies; they only develop them if sensitized (exposed to $Rh^{+}$ blood).

• Erythroblastosis Fetalis: Also called hemolytic disease of the newborn. Occurs when an $Rh^{-}$ mother, previously sensitized to Rh antigens, carries an $Rh^{+}$ fetus. Maternal antibodies cross the placenta and attack fetal RBCs.

ABO Blood Type Frequencies in the U.S. Population (%)