Blood Clotting: Pathways and Components

• Blood is a fluid connective tissue that circulates in vascular channels to all body tissues.
• Blood contains cellular elements like WBCs, RBCs, and platelets, all suspended in plasma.
• The circulating blood volume is about 5.6 liters in men and 4.6-6 liters in women.
• Blood accounts for about 7-8% of body weight in a 70kg person.
• Plasma accounts for about 55% of blood volume, approximately 3L.
• The formed elements make up between 43-45% of the total blood volume.

Characteristics of Blood

• Oxygenated blood is bright red.
• Deoxygenated blood is dark red or purplish.
• Blood is denser than pure water.
• Blood has a pH range of 7.35 to 7.45, making it slightly alkaline.
• Blood temperature is slightly warmer than core body temperature, around 100.4°F.
• Typical blood volume in adult males is 5-6 L.
• Typical blood volume in adult females is 4-5 L.
• Blood constitutes about 8% of body weight.

Production of Blood Cells

• In fetuses, blood cells are formed in the yolk sac, later in the liver and spleen.
• In infants, blood cells are produced in the bone marrow of all bones.
• In adults, blood cells are formed in the bone marrow of long bones like the humerus and femur.
• Red marrow is the active marrow responsible for blood cell production.
• Yellow marrow is the inactive marrow.

Functions of Blood - Transport

• Transports amino acids, lipids, and carbohydrates (glucose).
• Transports minerals, vitamins, and hormones.
• Delivers oxygen (O2) and removes carbon dioxide (CO2).
• Maintains body temperature by distributing heat.
• Transports excess body water and immunoglobulins.
• Transports blood clotting factors and platelets.
• Transports waste products of excretory organs.

Functions of Blood - Homeostatic

• Regulates the interstitial fluid compartment.
• Maintains acid-base balance with buffers and body temperature.
• Facilitates protection against infection and blood clotting.

Blood Protection

• Blood's clotting ability(becomes gel-like) prevents excessive blood loss after injury.
• White blood cells protect against disease through phagocytosis.
• Blood proteins, including antibodies, interferons, and complement, protect against disease.

Cellular Components of Blood & Hemopoiesis

• All cellular components of the blood originate from the same multipotent uncommitted stem cell.
• Committed stem cells in marrow consist of 75% white blood cells and 25% red blood cells.
• Pluripotent stem cells in red bone marrow produce myeloid and lymphoid stem cells.
• Myeloid stem cells develop into red blood cells, platelets, monocytes, neutrophils, eosinophils, basophils, and mast cells.
• Lymphoid stem cells develop into lymphocytes and natural killer (NK) cells.
• Various stem cells in blood plasma have cell identity markers, but are not distinguished histologically and resemble lymphocytes.

Components of Blood

• Whole blood consists of blood plasma, a liquid extracellular matrix with dissolved substances
• Whole blood consists of formed blood elements which are cells and cell fragments.
• About 45% of blood is formed elements, and 55% is blood plasma.
• More than 99% of formed elements are red blood cells (RBCs).
• White blood cells (WBCs) and platelets make up less than 1% of formed elements.
• A thin buffy coat layer of WBCs and platelets is located between packed RBCs and plasma in centrifuged blood.

Erythrocytes (RBCs)

• Erythrocytes are mature, non-nucleated red blood cells with a biconcave shape.
• They have a diameter of 8.5 micrometers, an edge thickness of 2.5 micrometers, and a center thickness of 1.5 micrometers.
• There are approximately 5 million RBCs/mm³ of blood, varying between sexes.
• Males have 4.5-6 million cells/mm³, while females have 4.3-4.5 million cells/mm³.
• Variation in RBC count between sexes is due to testosterone in males, a red blood cell differentiation inducer.
• Greater muscle mass in males requires more oxygen supply, further affecting RBC variation.
• Red blood cell shape maximizes surface area for gas exchange and allows squeezing through narrow vessels.
• Glucose-6-phosphate dehydrogenase on cell membranes helps utilize glucose, O2, and ATP.
• Red blood cells have a lifespan of 120 days.
• Newborns have a higher RBC count than adults (6 million/mm³).
• Erythropoietin (EPO) stimulates RBC production in response to hypoxia, 85% from the kidney and 15% from the liver.

Erythropoietin (EPO)

• EPO is a glycoprotein containing 165 amino acid residues and 4 oligosaccharide chains.
• Erythropoietin induces differentiation and has a half-life of about 5 hours.
• Hypoxia stimulates EPO production, Cobalt salt and androgens can also stimulate it.
• Kidney produces 85% of EPO, liver produces 15%.
• The main site of EPO inactivation is the liver.
• Chronic renal disease adversely affects EPO production.
• Recombinant EPO is available for therapeutic use due to gene cloning.

Packed Cell Volume (PCV)

• A sample of blood treated with anticoagulant and spun in a centrifuge separates into layers.
• Red cells settle at the bottom and white cells settle on top forming the buffy coat.
• Hematocrit refers to the fraction occupied by red cells, normally about 45%.
• Male hematocrit is about 47%, and female hematocrit is about 42%.
• Values lower than normal hematocrit are an indicator of anemia.

Erythrocyte Sedimentation Rate (ESR)

• ESR measures the rate of red blood cell settling without centrifugation.
• ESR depends on cell shape, concentration of plasma proteins, and infection.
• Rouleux formation is the stacking of red blood cells.
• ESR monitors diseases recovery or treatment effectiveness and varies with age and sex.
• Newborns ESR = 2mm/hr and adult male ESR = 3-7mm/hr (5.7).
• Adult female ESR = 3-15mm/hr (9.5)

Requirements for RBC Production, Erythropoietin

• Erythropoietin is a glycoprotein with a molecular weight of 35 kdaltons.
• Erythropoietin contains 165 amino acid residues and 4 oligosaccharide chains.
• Primarily produced by the kidney (85%) and liver (15%), as well as astrocytes in the brain.
• Production is in response to hypoxia, resulting in the production of renal erythropoietic factor (REE) by the kidney.
• Erythropoietin stimulates red blood cell production from bone within 2 days.

Requirements for RBC Production, Iron

• Iron is absorbed from the first part of the small intestine via active transport.
• Ferrous iron (Fe2+) is absorbed 3x more rapidly compared to ferric iron (Fe3+).
• Iron forms the core element of the heme porphyrin structure.
• Iron combines reversibly with oxygen.
• The recommended daily intake is 0.5mg for males and 2mg for menstruating females.
• Transferrin (β-globulin) transports iron released when red blood cells break down to the liver.
• The liver stores about 60% of the body's iron as ferritin.
• Iron distributes in the body as follows: Hemoglobin (65%), Myoglobin (4%), Ferritin (15-30%), and Transferrin (0.1%).

Requirements for RBC Production, Vitamin B12

• It is vital for cell functions and tissue growth
• Is vital for synthesis if DNA
• Absorbed at terminal ileum, enhanced by intrinsic factor from parietal cells.
• 1ng maintains RBC production
• Leads to Pernicious anaemia with failure of nuclear maturation & cell division
• Other key materials needed for RBC Production
• 1. Folic acid
• 2. lipids
• 3. Protein
• 4. Amino acid

Hemoglobin

• The red oxygen-carrying pigment in red blood cells for vertebrates.
• Hemoglobin is a globular molecule, a protein with a molecular weight of 64,450.
• Has two parts: a heme portion and globin portion.
• Heme attaches to 4 polypeptide chains forming the globin portion.
• Heme contains a central iron domain.
• Fully saturated hemoglobin carries 4 molecules of Oxygen.
• Concentration averages about 14g/dl in females and 16g/dl in males.

Jaundice

• It is a clinical condition marked by yellowish discoloration of the sclera of the eyes and soft body tissues.
• Jaundice typically occurs when 300-500 ml of blood is hemolyzed in less than a day.
• Causes of jaundice include hemolysis, infection, toxic effects on liver cells, and obstruction of the bile duct

White Blood Cells (Leukocytes)

• Also known as leukocytes

• There are about 4,000-11,000 white blood cells/mm3 of blood

• Concentration Increases during infection

• Two main types of white blood cells: Granulocytes and Agranulocytes

• Granulocytes contain cytoplasmic granules that pick up stains.

• Granulocytes include;

  • Eosinophils: Stain bright red, 1-2 lobes on nucleus, 150-300 cells/mm of blood, represents 1-4 of WBC count, half life is 12-20 hours.
  • Basophil: stain blue, have no definate lobe, 0-100 cells/mm of blood, represents 1-4 of WBC count, half life is 12-20 hours
  • Neutrophil: Stain neutral, have 3-5 lobes, 3000-6000 cells/mm of blood, have a half life of 6 hours.

• Agranulocytes dont contain cytoplasmic granules that pick up stains

• Agranulocytes consist of:

  • Monocytes: Have a horse show shaped Nucleaus that take up 2/3 of the cytoplasm, 300-600 cells/mm of blood, represents 2-8 of WBC count, and have a half life from 72 hours to Months.
  • lymphocytes: Are released immature, Migrate into the tissues, enlarge up to five times and develop numerous cytoplasmic granules (lysosomes).
  • Macrophages: Monocytes after maturation becomes macrophages and are more powerful phagocytes than neutrophils
    • Macrophages have a powerful lysosomal lipase which breaks down the lipid-rich cell memebranes of many bacteria.
    • After 72 hours, they are transformed into tissue macrophages and can survive for months.
    • Are activated by lymphokines from T- lymphocytes and are called histocytes or wandering cells.
  • Some Examples of tissue macrophages are:
    • Kupffer cell of the liver
    • Pulmonary alveolar macrophages
    • Osteoclast in bones
    • Microglia cells in the brain and nervous system
    • Microphages of the lymph nodes
    • Macrophages of the spleen
  • Lymphocytes are of two main types:
    • B- lymphocytes: Responsible for humoral immunity i.e. they synthesize circulating antibodies.
    • T-lymphocytes: Processed by or in some way dependent on the thymus gland. Responsible for cell- mediated immunity i.e. the production of lymphocytes which are sensitized against specific antigens.
  • Lymphocytes include:
    • Lymph nodes: where reticulum cell in lymph node can change to lymphoblast which form lymphocyte, plasma blast which form plasma cell (immunoglobulins).

• Lymphocytes*

• Are produced from lymph nobes, thymus, spleen, and bone marrow

• Approximatly 1/4 of circulating leuocytes are lymphocytes. They are actively motile

• Consist of two main types. Lymphocytes B are responsible for humoral immunity and synthesize antibodies.

• T lymphocytes are processed in thymus and are responsible for cell mediated immunity

• Single Large nucles that occupies the cytoplasm in the concentration of 1500-4000 cells/mm3 of blood

• Contration is impacted/decreased by gucocortids from zonal fasculata of adrenal cortex

• WBC: 20-40%

• 200 days half life

• Reticulum cell in lymph node can change to lymphoblast

Lymph Node Examples

• Cervical Duct
• Thoracic duct lymph
• Auxillary duct
• Inguinal duct lymph

Key Aspects of Lymph Nodes

• WBC and All nucleated cells in the body have portiens called major histocompatibilty Antigens (MHC) that protrude from their plamsa membrane into the extracellular fluid
• These "cell identity markers" are unique for each person
• RBC posses blood groups but they lack the MHC Antigens

White Blood Cell, Neutriphil, Eosiphiphil, Basophil

• Function of WBC, most live a few days, and the live of hours During infection
• Far less numerous than red blood cells; and are at about 4000 - 11,000 cells per microliter of blood
• An increase in the number of WBCS above 11,000/L, is a normal response and protective
• An abnormally low level of white blood cells (below 4000/L) is termed leukopenia.
• WBC can leave the bloodstream by a process termed emigration also called diapedesis
• Molocules known adhesion molecules help WBC stick to the endothium
• A sign of inflamed tissue attracts phagocytes, a phenomenon called chemotaxis

Substances that provides Chemotaxis

• Tokins produced by migrobes, specialized products of damaged tissues
• CSFs and Neutrophils react fast to bacteria destruction
• Chemical include enzyme lysozyme a strong oxidant

Definsins

• Are Protein w antiboteic avtivity against bacteria and fungi
• Eosinophils release enzymes like histminase that combat iflammation and alergies
• H. Eosiniphil often indicates allearic condition

Bastophils

• At infmation release heparin, histmine and serotonin
• Indensify the infmatory reaction and allergic reation
• Similar to mast cells
• Lymphocytes are major soldiers in lyphatic system
• Three manin typr of lympohytes are B cells, T cells, and natural killeer B celss efftive in destryong barctera
• T cells atk virusus , fugin transplanted cells
• immune and nk cells atk wide variety of infectious tumor cells
• In conclusion number of wbv increase indicated infamation and disease
• Physician will order white blood test to determne efdects of poisons Play a differentrole

Platelets

• Develop into stem cells and duffreienate into plateletes
• Develop into procursers callled megokaryoblast

Megalyokast

They plitners inte 2000 to 3000 gragmetns plateletes form the megakarytces in red marrow- and entre circulation 150000 in each Micrometer 4 mm in diameter promote blood clotign platelets have a 5-9 day life span

Blood Groups

Based on the two types of agglutinogens on the surface of red blood cells called A and B which react with antibodies or agglutinins forming the four blood groups (plasma) (red cell) Agglutinin Agglutinogen Α β B β B α AB AB Nil O α and β O Nil

• Do not have antibodies that react from your own rb
• if Bloood is b u have B antignes and atni a
• Are mucopolysaceharides secretion, liver

24 lood groups and 100 antigens on suragce lewis Kell kidd and Duffy for trahsiosn donor red cellls a=85 shows callled Rh agglutinogen

• This is present addition to a b called rh
• blood will be called Rh, if the rh aggluntiogen is absent
• normally plasma doeas not contain anti RH antibodies If RH person reciesves a rh bllod trnfusion, however, the immune system starts to make antib RH A transfusion is given to anemic for example a Severe hemhorare or improve immuntity
• antibodies caused glumination aglutination -antibody response

Transfusions

• Incompatible blood transfusions can cause antibodies in the recipient's plasma bind to antigens on the donated cells, resulting in agglutination and RBC clumping.
• The antigen-antibody complexes activate plasma proteins of the complement family.
• Complement molecules rupture the donated RBCs, releasing hemoglobin into the blood plasma and causing haemolysis.
• Liberated hemoglobin has the potential to cause kidney damage.
• Type O blood are considered universal donors
• This is not the practice use of a universal recipient and donor

Hemolytic Disease of the Newborn (HDM)

• Common with Rh incompatibility no direct bllod transfusision during pregny Rh-mother, the mother will start to anti-RH First born baby is is not affedted, if mother beces pregnnat a gain atni RH bllod can pass rh there is b problem agllutination may occur injectoin can be gicen to prevent hdn inactiate rhe Fetal antihs ahtigns

Haemastasis.

not to be confused with the tern hemostasis, and is of responsis must be quick localized vascular plate clot clotign

• hemorage Vascular spasm artories dmage smooth us cle in the walls contratcs vascular spam for hours minutes till the other take place

Platelet formation

• Store an array of of chemical , such as clotign factors Enzyme , theomin Glycogen Plaltele

Platelet PLug Formation

• Platete contact and cstick to collage fibers Become active an dliebrated aD-C sErotomuna nd thominxane A function o vasocntrticsutrs efftive In smll vessrls , and gets tight with with fbirn

Bllood clotting

• Normnaly blooids in liquid the body it gets thick is is acalled blod dot consisiting of fobrin ,clotitng or caogiualtioon a seirse of chela reactions that formate fibrin dhts=
• blood dclt to to to

Coagulation Pathways

Clotting is complex casde enyzmatic reactiions in which in fixed seguence the Extrnisc pathway The Intrinsic pathway pro thrmobiase converts into trhombitn thomin bcoverts into fibrein

extnsic w fewer step and severe trauma issue factor leaks into blold from cell

innntstic pathway is slow need to the direct contact the activtors with the intistic

Common Pathway

• Formation is pro thrmobiase thormbjn trhombin fibrin

Thre is a clot is for ed retraction a clot

normal retaction depebd e

Role

• Coafltion facotrs and clooitn and bacte
• and vitamin K

Plasma

• Plsma fluod and consists water 92 and protein 68 and lips .6 and glucose1 plasma proteid damage damge d

plasma proetin vicostiy osmitic reurn

• and suspensijion aminocit and resrrves hormnes urea

ALBUMB1IN

• 50% of blod abunnt

GLOBULIN

About 20% of plasma protreinnn

FIBRINOGENS

315

• 3ml blood clot

Immunity

reists inavasiony non specific

Acioured Immunity

• Involves protduaction of specific antibody thwer are two forms of immunty hmolal and celluar

Humoral Immuntiy

Thsi os immunity fporucr by c circuylting antibodes

CDelluars Immunity

Lymkocytes

macophates after atjken comvine wtuh the class major hsitcomaptibilty. combine wtijth eh help t ceel

Explore the intricacies of blood clotting, covering the roles of prothrombinase, thrombin, and Factor X in the common, extrinsic, and intrinsic pathways. Understand the significance of Vitamin B12 and the impact of platelet damage.