Blood psio

• PSIO202 covers the physical properties of blood and erythrocytes, including leukocytes and thrombocytes.

Objectives

• Identifying the origin and production of various white blood cells is essential.
• Understanding the characteristics and functions of white blood cells is critical.
• White blood cell types are categorized based on staining.
• Anatomy, physiology, and the relevance of phagocytosis are important to understand.
• Structure, function, and production of platelets are covered.
• Chain reactions that control blood loss after an injury are discussed.
• The series of events leading to platelet plug formation is studied.
• Key elements of the extrinsic and intrinsic clotting pathways are diagrammed, compared, and contrasted.

Leukocytes

• Leukocytes are also known as white blood cells (WBCs).
• All WBCs (leukocytes) have a nucleus but lack hemoglobin.
• WBC classification is granular versus agranular, based on the presence of cytoplasmic granules visible through staining.
• Granulocytes include neutrophils, eosinophils, and basophils.
• Agranulocytes include monocytes and lymphocytes.

Hematopoiesis of WBCs

• Myeloid stem cells produce megakaryocytes with a diameter of about 160 µm.
• Thrombopoietin, or TPO, causes fragments to slough off the megakaryocyte.
• 2,000-3,000 fragments, or platelets, enter the circulation.
• Each platelet is ~2-4 µm in diameter and ~1 µm thick.

WBC Physiology

• WBCs are less numerous than RBCs, with 1 WBC for every 700 RBCs.
• Leukocytosis is a high white blood cell count, potentially due to microbes, strenuous exercise, anesthesia, or surgery.
• Leukopenia signifies a low white blood cell count, which can be caused by radiation, shock or chemotherapy.
• Only 2% of the total WBC population is in circulating blood at any given time.
• The remainder of WBCs are in lymphatic fluid, skin, lungs, lymph nodes, and the spleen.

WBC Emigration

• WBCs roll along the endothelium, stick to it, and squeeze between cells.
• Adhesion molecules, specifically selectins, aid WBCs in sticking to the endothelium.
• Selectins are displayed near the site of injury.
• Integrins found on neutrophils assist in movement through the vessel wall.

Phagocytosis

• This refers to the "cell eating" of bacteria.
• Neutrophils and monocytes perform it avidly
• Eosinophils perform it weakly
• Phagocytosis includes chemotaxis, adherence and ingestion, and destruction.

Chemotaxis

• Chemotaxis involves the attraction of phagocytic cells to the site of infection.
• Chemicals released by the pathogen and/or infected cells attract the phagocytes.

Adherence & Ingestion

• Adherence is the attachment of the phagocyte to the pathogen's membrane.
• Enveloping pseudopodia facilitates ingestion, resulting in a phagosome.

Destruction

• This is initiated when the phagosome fuses with a lysosome, resulting in a "phagolysosome."
• Lysozymes and other destructive chemicals from the lysosome destroy the membrane and internal structures of the pathogen.
• Residual fragments of the dead pathogen can be removed from the cell by exocytosis.

Bone Marrow Transplant

• A clinical application involving intravenous transfer of healthy bone marrow
• The procedure involves destroying "sick" bone marrow with radiation and chemotherapy.
• A donor marrow sample is put into the patient's vein for reseeding of bone marrow.
• Success depends on the histocompatibility of the donor and recipient.
• Stem cells can be transplanted instead of bone marrow and can be "autologous."
• Conditions like leukemia, lymphoma, multiple myeloma, sickle-cell anemia, aplastic anemia, and breast, ovarian, or testicular cancer can be treated through this method.

Thrombocytes (Platelets)

• Platelets are cell fragments that circulate for 5-9 days and then die.
• Approximately 2/3 of platelets circulate, while 1/3 reside in the spleen.
• A thrombus is a clot.
• Thrombosis is clot formation.
• Embolus is a circulating blood clot.
• Hemorrhage is severe, uncontrolled bleeding.

Hemostasis

• This involves a series of reactions to stop bleeding.
• It occurs in three phases:
• Vascular spasms (immediate vasoconstriction in response to injury).
• Platelet plug formation.
• Coagulation (blood clotting).

Vascular Spasm

• Occurs only in vessels with smooth muscle in the wall.
• It is a reaction to injury.
• Reduces vessel diameter.
• Stops blood flow almost instantly.
• Effective only in small vessels.

Platelet Plug Formation

• Platelets normally do not stick to each other or to the endothelial lining of blood vessels.
• Upon damage to a blood vessel, platelets stick to exposed collagen fibers.
• Activated platelets stick to one another.
• Liberated thromboxane A2, serotonin, and adenosine diphosphate (ADP) attract and activate more platelets.
• ADP makes platelets sticky.
• Thromboxane A₂ and serotonin cause cell contraction.
• All of this results in a tight platelet plug formation.

Blood Clotting (Coagulation)

• This involves a set of reactions in which blood is transformed from a liquid to a gel.
• The process is highly complex, involving approximately 30 substances.
• There are 13 clotting factors involved, most originating from the liver.
• Blood clotting has both intrinsic and extrinsic pathways.
• The intrinsic pathway is generally slower compared to the extrinsic pathway.
• Prothrombin, fibrinogen, and factors V, VII, IX, and X are synthesized in the liver.
• Vitamin K is essential for synthesizing factors II, VII, IX, and X.
• Vitamin K deficiency can result in blood clotting failure.
• Individuals lacking factor VIII are diagnosed as hemophiliacs.
• Tissue plasminogen activator, thrombin, and plasminogen react to form plasmin.
• Plasmin digests fibrin strands and breaks down the clot.

Common Pathway for Blood Clotting

• The final three steps constitute the "common pathway," essential for effective clotting.
• Prothrombinase, once activated, converts prothrombin into thrombin.
• Thrombin converts fibrinogen (soluble) to fibrin (insoluble, stable threads).
• Thrombin activates factor XIII, which stabilizes the fibrin network.

Fibrinolysis

• Fibrinolysis equals clot breakdown.
• Clots must dissolve to prevent becoming an embolus in the circulation.

Body Fluids

• Blood and interstitial fluid service cells.
• Nutrients and oxygen reach cells via diffusion from blood to interstitial fluid.
• Wastes move in the reverse direction. Hematology specifically studies blood and its disorders.

Blood Composition

• Plasma, around 91.5% water and 8.5% solutes, is a clear, straw-colored liquid.
• Formed elements are the cells and fragments in blood.

Blood Plasma

• Made of over 90% water.
• ~7% plasma proteins (created in the liver and confined to the bloodstream).
• Albumins maintain blood osmotic pressure.
• Globulins (immunoglobulins) such as:
• Antibodies that bind to foreign substances called antigens.
• Forming antigen-antibody complexes.
• Fibrinogen is for clotting.
• ~2% other substances: electrolytes, nutrients, hormones, gases, wastes.
• Blood serum is blood plasma without both fibrinogen and other clotting factors.

Formed Elements of Blood

• Include red blood cells (erythrocytes or RBCs).
• White blood cells (leukocytes or WBCs).
• Granular leukocytes: neutrophils, eosinophils, basophils
• Agranular leukocytes: lymphocytes (T cells, B cells, and natural killer cells), monocytes.
• Platelets are also included. Erythropoietin (EPO), the hormone which stimulates erythrocytes

Platelets

• The major contributor to blood clotting.
• Often called thrombocytes.
• Are irregularly shaped cell fragments with a diameter of ~2-4 micrometers.
• The human body has ~150,000-400,000 platelets per microliter of blood.

Hematocrit

• The % of blood that is occupied by RBCs.
• Normal ranges are:
• Female 38-46% (42% avg).
• Male 40-54% (46% avg).
• Testosterone stimulates EPO synthesis.
• Anemia: not enough RBCs (or hemoglobin) for proper O₂ transfer.
• Polycythemia: an excess of RBCs (over 65%).
• Caused by Dehydration, tissue hypoxia, or blood doping in athletes.

Erythrocytes

• Also known as red blood cells or RBCs.
• Shaped like biconcave discs.
• Shape increases the surface area available for oxygen binding.
• Averaging ~ 8 µm in diameter.
• They lack a nucleus.
• Deform easily and can change shape.
• Stacked (in rouleaux formation) in larger blood vessels.
• Parachute shapes in small arterioles and venules.
• Bullet shapes in capillaries

Hemoglobin (Hb) Protein

• Hemoglobin's composition includes:
• 'Globins': 4 large protein chains (2 alpha and 2 beta chains).
• A heme group (contained within each chain).
• The heme group contains:
• A porphyrin ring that surrounds a single iron molecule.
• Each iron in heme can bind one molecule of oxygen (O2), so each Hb binds 4 molecules O2.

Hemoglobin Functions

• All hemoglobin molecules can carry 4 O2 molecules.
• Oxygen is bound by hemoglobin in RBCs in blood flowing through lung capillaries.
• The oxygen is then transported to the body's cells by systemic circulation.
• Hemoglobin transports 23% of the total CO2 produced in tissue cells.
• The CO2 binds to amino acids in the globin portion of hemoglobin (Hb), NOT with heme.

Hemoglobin Concentration in Blood

• 16 g/dL (g/100mL) of blood in men.
• 14 g/dL (g/100mL) of blood in women.
• Hematocrit and hemoglobin levels are how anemia is diagnosed

Erythropoiesis

• Is RBC formation.
• It occurs in the red bone marrow.
• After birth, stem cells form RBCs. Stem cells differentiate into proerythroblasts. Then proerythroblasts become erythroblasts then reticulocytes.
• As a reticulocyte matures, hemoglobin will be produced and its nucleus is ejected.
• The cell matures and then becomes an erythrocyte.

Hemopoietic Growth Factors

• Help regulate differentiation and proliferation of blood cells.
• Erythropoietin (EPO) is produced by kidneys and stimulates erythropoiesis by increasing RBC precursors).
• Thrombopoietin (TPO) which is liver-produced, it stimulates platelet formation.
• Local hormones of bone marrow called Cytokines includes: stimulate proliferation in other marrow cells. colony-stimulating factors (CSFs) & interleukins that stimulate WBC production.

Medical Usage of Growth Factors

• Achieved through recombinant DNA technology.
• Recombinant erythropoietin (EPO) can treat decreased RBC production of end-stage kidney disease.
• Given to stimulate WBC formation in cancer patients receiving chemotherapy, as it kills off bone marrow.
• Thrombopoietin (TPO) helps and works to prevent platelet depletion during chemotherapy.

Life Cycle of Erythrocytes (RBCs)

• They live for only 120 days.
• They wear out from constantly bending to fit through capillaries.
• Have no means to repair nucleus as as such, they get removed.
• Worn out RBCs get removed by marophages in the spleen and then liver.
• Breakdown products are later recycled.

Destruction and Recycling of RBCs

• Is facilitated via macrophages of the liver or spleen.
• During destruction and recycling;
• Globin gets broken down into amino acids and then recycled.
• Heme gets split into iron (Fe+3) & biliverdin (green pigment).
• Iron (Fe+3).
• Is transported in blood attached to transferrin protein.
• It's stored in the liver, muscle or spleen attached to ferritin or hemosiderin protein.
• Or transported to bone marrow for hemoglobin synthesis.
• Biliverdin (green) gets also converted to bilirubin (yellow).
• Bilirubin is secreted via what's secreted in the liver as part of bile, where it's transported for digestion).
• Bile breakdown products get excreted via kidneys & intestine.
• In the large instestine;
  • Bilirubin gets converted to urobilinogen, where some urobilinogen is either: reabsorbed, converted into urobilin, and then excreted via the kidneys in urine,
• Or stercobilin leaves as feces.