Dentistry BLOOD 2025-1 PDF

Physiology Blood MHR 0  BLOOD Extracellular fluid (ECF) 8% of the body weight= 5.6 L in adult male. Circulating in blood vessels throughout cardiovascular system (CVS) by pumping action...

Physiology Blood MHR 0  BLOOD Extracellular fluid (ECF) 8% of the body weight= 5.6 L in adult male. Circulating in blood vessels throughout cardiovascular system (CVS) by pumping action of the heart Composition of the blood Plasma (55%) = 3.5 L, (5% of the body weight) Cells (45%) Clear Yellow fluid Clots on standing→ remaining fluid is serum Composition of Plasma 1. Water (90%) 1. Red blood corpuscles 2. Organic substances (9.1%): 2. WBC’s (leucocytes) Protein 3. Platelets (thrombocytes) Lipid Glucose Waste, vitamins 3. Inorganic (.9%): Na+ (chief cation) Cl- (chief anion) HCO3, Phosphate, sulphate 4. Blood gases: O2, CO2, N2 1  Plasma Proteins Concentration= 7.2 - 7.4 g/dl): dl=100ml Types Albumin Globulin α, β, γ Fibrinogen Prothrombin Concentration (3.5-5 gm/dl) (2.5) (0.4) (0.01) Molecular weight 69,000 90,000- 156,000 340,000 68,700 Albumin: Highest concentration, Lowest molecular weight Sites of Formation 1. Albumin, fibrinogen, prothrombin: in liver 2. Globulins: o 50% in liver (α, β) o 50% in plasma cells of Reticuloendothelial system (γ globulin) Albumin/Globulin Ratio (A/G) = 1.2-1.6. decreased in: Liver diseases (cirrhosis , hepatitis) Kidney diseases (nephrosis) Infection ↓formation of albumin ↑loss of albumin in urine (↑ -globulins) Due to its small molecular size N.B. RES=Diffuse system of cells present in liver, spleen, lymph nodes, bone marrow 2  Functions of Plasma Proteins 1. Osmotic Function: total osmotic pressure of plasma = 5000 mmHg Colloidal (oncotic) pressure Crystalloid osmotic pressure Due to Plasma proteins (albumin) Crystalloids (Na+, Cl- , HCO3) Power 25 mmHg (Weak) Remaining (more powerful) Importance important osmotic effect less important Cause Cannot diffuse through capillary diffuse through capillary Kept inside the plasma Plasma conc. =interstitial fluid conc. Main re-absorptive (draw) force Net osmotic effect = zero Regulate fluid exchange and blood volume 2. Capillary function partially block capillary pores → limit permeability. (maintain normal permeability) 3. Transport by Albumin & globulin ( &), prevent loss of substances (hormones, vitamins, lipids and minerals) in urine 4. Defensive by -globulins (immunoglobulin) (antibodies) defend the body against microorganisms & toxin 5. Blood clotting by Prothrombin & fibrinogen 6. As a source of amino acid for tissue Plasma proteins act as Labile protein stores for tissue (Dynamic structures in continuous turnover) 7. Viscosity: Blood is 3-5 times as viscous as water/ plasma is 1.5 times as viscous. Plasma viscosity due to fibrinogen (large size & elongated shape). Importance of Viscosity o Prevent rapid flow of blood from arteries to veins o Responsible for resistance→ maintains arterial blood pressure 8. Buffer: any buffer consists of weak acid and strong base 15% of buffering power of blood. At normal pH (7.4) slightly alkaline: ✓ proteins carry – ve charge ✓ → form proteinic acid (weak acid) and Na proteinate (buffer system) Maintain pH 7.4 in spite of addition of acids or alkalis. 3  Erythrocytes (RBCs) Shape biconcave discs Size 90 m3 Count Sex Adult male: 5.4 million/mm3 Female: 4.8 million/mm3 Age ↑ in new born infants ↓in old age ↑ athletes & at high altitudes Structure: o No nuclei "corpuscles" , No mitochondria (Energy from anaerobic glycolysis) o Contain ✓ Hemoglobin ✓ K+ (main intracellular cation) ✓ Carbonic anhydrase (C.A.) enzyme for CO2 transport o Biconcave & plastic Advantages: A. ↑ Surface area. B. ↑ Flexibility →squeezed in capillaries without rupture. C. Result in minimal tension on membrane when volume ↑in venous blood due to CO2 transport Hemoglobin Is the red oxygen-carrying pigment of RBC's Hemoglobin % (content): amount of Hemoglobin in grams / 100 ml blood. Adult male 15-16 g/dl Female 13-14 g/dl Newborn 19 g/dl Structure & types of hemoglobin: (4 subunits), formed of Polypeptide chain (4 chain → globin) Heme (4) Adult Hb (HbA) Fetal Hb (HbF), differ in amino acids Fe2+ (ferrous iron) + 22 22 protoporphyrin O2 affinity > HbA Facilitates O2 movement from maternal to fetal blood. 4 Functions of RBCs A. Functions of Hb 1) Gases Transport: (O2 from lung to tissue, CO2 from tissue to lung) C. A − CO2 + H 2O ⎯⎯⎯→ H 2CO3 → H + HCO 3 2) Buffer H+ inside RBCs (formed during CO2 transport) → result in minimal change in PH 6 times buffering > plasma proteins Deoxy-Hb (dissociate less, form weak acid) strong buffer > oxyhemoglobin B. Functions of Membrane: 1) Biconcave & Plastic: ? 2) Keeps Hb inside. ❖ If Hemoglobin become free in the plasma → it will Pass to kidney → block renal tubule → causes renal failure ↑blood viscosity → ↑blood pressure & cardiac work ↑ colloidal osmotic pressure →prevent filtration→ ↑blood volume & cardiac work Life Span 120 days. Fate of RBCs Old RBCs (fragile), Rupture when pass via narrow vessel in spleen 5  ERYTHROPOIESIS: Formation of new RBCs Sites In fetus Liver (mainly) & spleen. After birth Red bone marrow of all bones. By age Red marrow in long bones → inactive (replaced by fat) After 20 y Only flat membranous bones: ✓ Skull ✓ Sternum ✓ Ribs ✓ Vertebrae ✓ Pelvis Factors Affecting Erythropoiesis I. O2 supply – Role of Erythropoietin: RBCs production ↑ in hypoxia Hypoxia (↓O2) as in Hemorrhage High altitude Heart failure Lung diseases Athletes loss of RBCs ↓ O2 tension ↓ blood flow ↓ O2 diffusion Relative O2 deficiency in atmosphere (↑requirements) Hypoxia → stimulate Erythropoietin release Glycoprotein hormone, molecular weight = 35,000 Present in the plasma at low concentration / half life = 5 hours Sources: In adults: ✓ 85% is formed by endothelial cells of peritubular capillaries in kidneys, ✓ 15% by tissue macrophage cells in the liver (Kupffer cells) Anemia develops in renal failure, liver cannot compensate Mechanism of action accelerates steps of erythropoiesis Stimulation of secretion of erythropoietin: 1. Alkalosis (high altitude) Androgens Adenosine Adenosine antagonist inhibit its secretion 2. β agonists 3. Cobalt salts 4. Hypoxia (main stimulus) 6 II. Hormones ✓ Thyroxin (regulate metabolism) ✓ Glucocorticoids ✓ Androgens stimulate erythropoietin formation III. Healthy Bone Marrow site of erythropoiesis Bone marrow is destroyed by: ✓ X-rays ✓ Radiation ✓ Antibiotic (chloramphenicol) ✓ Sulpha drugs ✓ Malignant tumor Result: ↓ all blood cells → cause aplastic anemia. IV. Healthy Liver forms Globin of hemoglobin 15% of erythropoietin. Stores vitamin B12 and iron liver diseases associated with anemia V. Diet A. Proteins: High biological value for formation of globin. B. Vitamins: esp. vitamin C, B12 and folic acid. 1. Vitamin B12 = Cyanocobalamine = Extrinsic Factor = Maturation Factor Functions of vitamin B12: essential for DNA formation & nuclear maturation of RBCs (division of RBC’s) transformation of mRNA into DNA Essential for metabolism & Formation of myelin sheath Absorption of vitamin B12: Parietal cells of fundus of the stomach → secrete intrinsic factor (glycoprotein) combine with vitamin B12 → Protect vitamin B12 From digestion by GIT enzymes Pancreatic Trypsin: is also required Absorbed from terminal ileum→to blood 7  Causes of deficiency: 1. Absence of intrinsic factor due to atrophy of gastric mucosa (Pernicious anemia) 2. Removal of stomach (gastrectomy 3. ↓ Intake (rare) 4. ↓ Absorption: diseases of lower ileum 5. ↓ storage: Liver diseases Effect of deficiency: 1. Macrocytic / megaloblastic anemia: due to Failure of division of erythroblast in bone marrow →↓ number, ↑ size (fragile) (megaloblasts and megalocytes ) →↓life span 2. Neurological symptoms Treatment of deficiency: Vitamin B12 injection. 2. Folic Acid: one of vitamin B complex Functions: DNA formation & nuclear maturation of RBCs→ (division of RBC’s) Effect of deficiency: Macrocytic anemia. Causes of deficiency: 1. ↓ Intake (dietary deficiency), esp. during pregnancy (↑requirements). 2. ↓ Absorption→ Diseases of GIT 3. Treatment of cancers with antifolate cytotoxic drugs 8 3. Iron Total body iron (4 g) and functions 70 % In hemoglobin 3% In myoglobin 1% In oxidative enzymes 26 % stored in liver and spleen Mechanism of Iron absorption, transport and storage Vitamin C (ascorbic acid) Dietary iron {bound ferric (Fe3+) non absorbable → Fe2+ (ferrous) Gastric HCl dissolve, facilitate reduction Phytic acid (in cereals), oxalate & phosphates form insoluble iron salts→ prevent absorption Absorption: in upper small intestine (duodenum) by active process Carried: by Transferrin (plasma proteins) in blood to Bone marrow Muscle Excess stored in liver &spleen To form Hemoglobin Myoglobin Ferritin Effect of deficiency Microcytic hypochromic anemia. Causes of deficiency: 1-↓ intake in diet: In infants fed milk (milk poor in iron), in females (during pregnancy &lactation). 2-↓absorption: Partial gastrectomy →↓ HCl Vitamin C deficiency ↑Phytic acid, oxalates and phosphates in diet Diseases of duodenum 3- Chronic blood loss: e.g Excessive bleeding during menstruation, bleeding peptic ulcer, piles Iron stores: insufficient Dietary iron can't compensate for iron lost 4. Trace Elements Copper: co-factor for HB synthesis , not enter into its formation Cobalt: stimulates erythropoietin secretion & enters in vitamin B12 formation. 9  ANEMIA Definition ↓ Oxygen carrying of the blood due to ↓ number of RBCs or ↓ Hb content Classification & Causes of Anemia: Normocytic Normochromic Anemia Microcytic Hypochromic Macrocytic Anemia (Iron Deficiency Anemia) (Megaloblastic Anemia) ↓Number ↓Number ↓ number Normal MCV (size) ↓ MCV ↑ MCV Normal MCH (hemoglobin content) ↓ MCH ↑MCH (hyperchromic) Causes Causes: Causes: 1- Hemolytic Anemia (↑breakdown) : vitamin B12 or iron deficiency???? Infection: streptococci, malaria folic acid deficiency Incompatible blood transfusion Snake venom, chemical poisons (benzene) 2- Hemorrhagic Anemia Acute (sudden, rapid) Blood Loss Body replaces plasma 1-3 days (diluted blood) RBCs: 3-4 weeks 3- Aplastic Anemia (Bone Marrow Depression) →↓all blood cells, causes…………….. HEMOSTASIS Definition Stoppage of bleeding from injured vessel. Consists of: A. Local VC of injured vessel B. Formation of Temporary platelet plug (platelet reactions) C. Formation of clot → stabilize temporary plug I. Local Vasoconstriction (immediate)→↓blood flow & allows platelets to adhere at site of injury. May be so strong, & completely obliterates the lumen of the injured vessel VC due to: 1. Nervous reflexes: initiated by pain sensation from traumatized vessel. 2. Local myogenic contraction: due to direct damage of the blood vessels Degree of contraction α amount of damage Transverse cut → cause more spasm > longitudinal cut. 3. Chemical substances: serotonin, thromboxane A2 released from platelets. 10  II. Formation of Temporary Hemostatic Plug: (platelet reactions) Can stop blood loss completely in small injury 1. Platelet adhesion: via receptors to ▪ exposed subendothelial collagen & ▪ von Willebrand factor. 2. Platelet activation ▪ adhesion → activates platelets ▪ → swell, change shape, put out pseudopodia, stick to other platelets ▪ → their contractile proteins contract ▪ →releasing granules 3. Platelet Release reaction: of Dense granules: non-protein e.g. ADP, serotonin, calcium Alpha granules: ) proteins( e.g. Some clotting factors (factor 13), PDGF ❖ Platelet-derived growth factor (PDGF) → stimulate growth of endothelium, smooth muscles ❖ Platelet activating factor (PAF): Membrane phospholipids PAF Arachidonic acid Cyclooxygenase Prostaglandin Thromboxane synthase Prostacyclin synthase (Of platelets) (Of healthy endothelium) Thromboxane A2 prostacyclin 1. VC 1. VD 2. ↑Platelet release 2. inhibit Platelet release 3. ↑Platelet aggregation 3. inhibit Platelet aggregation ✓ Prostacyclin opposite to thromboxane A2 → keeps platelet plug localized to site of injury And prevent spread of clot to the healthy area ✓ Aspirin inhibits COX→↓ thromboxane A2 & prostacyclin ✓ Endothelial cells can produce new COX within hours, Platelets cannot. ✓ Daily intake of aspirin →↓clot formation & prevents myocardial infarctions. 11 4. Platelet aggregation: by ADP, thromboxane A2, PAF → cause aggregation→ more activation → more release → self-propagating process → end in platelet plug formation 5. Platelet pro-coagulant activity ▪ platelet factor 3 (PF3) is exposed on platelet membrane ▪ PF3 start blood coagulation by activating some clotting factors. 6. Platelet irreversible fusion: by ADP, platelet enzymes. During blood coagulation, fibrinogen, attached to the membrane of aggregated platelets, is converted to fibrin threads, forming a tight plug after 24 to 48 hours 12  III. Blood Coagulation (Blood Clotting) o By clotting factors" plasma proteins" (mostly -globulins) o Proteolytic inactive enzymes, When activated→ activate other → end in clot formation o According to source of lipoprotein involved in clotting mechanism: A. Intrinsic Pathway : as Pphospholipid from platelet (PF3) i.e. in plasma. Contact with subendothelial collagen (in vivo) Contact with -ve charged wet surfaces e.g. glass of test tube (in vitro) 1. XII XII a Accelerated by (HMW) kininogens & kallikrein in plasma 2. XIIa activate XI 3. XIa activate IX 𝐏𝐡𝐨𝐬𝐩𝐡𝐨𝐥𝐢𝐩𝐢𝐝 + 𝐂𝐚 4. IXa form complex with VIIIa (activated by thrombin) → activate X B. Extrinsic Pathway: (phospholipids from outside) 1. Damaged tissues (in vivo) → release thromboplastin (TPL, factor III) → activate VII→ VIIa 2. VIIa in presence of phospholipid , (TPL) + Ca → activate X direct or indirect via activation of IX The common pathway 𝐗𝐚 𝐢𝐧 𝐩𝐫𝐞𝐬𝐞𝐧𝐜𝐞 𝐨𝐟 (𝐩𝐡𝐨𝐬𝐩𝐡𝐨𝐥𝐢𝐩𝐢𝐝+ 𝐂𝐚 + 𝐕) 1. Prothrombin → thrombin 𝐓𝐡𝐫𝐨𝐦𝐛𝐢𝐧 2. Soluble Fibrinogen → insoluble fibrin monomer+ 2 pairs of polypeptide chains (fundamental reaction) 𝐩𝐨𝐥𝐲𝐦𝐞𝐫𝐢𝐳𝐞 3. Fibrin monomer → form loose mesh 𝐜𝐫𝐨𝐬𝐬−𝐥𝐢𝐧𝐤𝐚𝐠𝐞𝐬 𝐯𝐢𝐚 𝐗𝐈𝐈𝐈 & 𝐜𝐚𝟐+ 4. Loose mesh → 𝒄𝒐𝒏𝒗𝒆𝒓𝒕 𝒕𝒐 tight (dense ) fibrin clot (stabilization) (XIII is activated by thrombin in presence of Ca) 5. Contraction of actin & myosin of Platelets → cause clot retraction →squeezes serum 6. Serum: is devoid of prothrombin, fibrinogen, factors V, VIII, XIII (consumed in clotting) 7. Net: formation of clot= fibrin thread (Platelets, blood cells and plasma entrapped in the clot). 13 Important notes 1. In the body, following injury, Clotting initiated by both systems. (exposed collagen, TPL) 2. Extrinsic system is rapid (15 sec), intrinsic system is slow (1-6 min). 3. In intravenous thrombosis, clotting by intrinsic system, via exposure of subendothelial collagen. 4. In test tube, clotting by intrinsic system only (glass or addition of collagen). 5. Action of Thrombin ▪ Activates fibrinogen→ fibrin ▪ Activate fibrinogen group (5,8,13) ▪ Accelerates actions of factors (9,10,11) ▪ Accelerates formation of more thrombin from prothrombin ▪ Accelerates platelet aggregation ▪ As soon as a small amount of thrombin is formed, clotting reactions are markedly enhanced by thrombin ▪ Clot continues to grow until stopped by limiting reactions. 14  Anticlotting Mechanisms = Limiting Reactions Aim prevent blood clotting in healthy blood vessels & break down any already formed clots. A. General limiting reactions Smooth vascular endothelium prevents activation of platelets & factor XII. Rapid blood flow & removal of activated clotting factors & their inactivation in liver. slow blood flow favors intravascular thrombosis Heparin (natural anticoagulant). B. Specific limiting reactions 1. Thromboxane A2 & prostacyclin: ‫الرسمة‬ 2. Antithrombin III: circulating inhibitor of blood coagulation→ bind & block activity of IX, X, XI (binding facilitated by heparin) 3. Fibrinolytic System: Except those in cerebral microcirculaion Express Thrombomodulin Thrombin Plasmin (fibrinolysin): lyses fibrin & fibrinogen→ fibrinogen degradation products (FDP) → inhibit thrombin. Plasmin= is the active component of fibrinolytic system 15  Anticoagulants Definition substances prevent blood clotting. A. In vitro anticoagulants prevent clotting outside body, e.g. in a test tube: 1. Removal of Ca2+ ions: Oxalates precipitate Ca2+ as salt Citrates (used in blood transfusions) deionizing Ca2+ ions (bind them) 2. Silicon coated tubes prevent activation of factor XII. 3. Heparin. B. In vivo anticoagulants prevent clotting in body. Heparin Dicumarol Origin Mast cells and basophils Plant Mode of Action Facilitates action of Antithrombin III → Competitive inhibition of vitamin K: blocks activity of IXa, Xa, XIa, XIIa inhibits formation of II, VII, IX, X Site of Action In vivo and in vitro Only in vivo Onset Rapid Slow Duration Short long Administration injection Orally Abnormalities of Hemostasis 1) Thrombocytopenic purpura: Platelet deficiency < 50,000/mm3→ causes subcutaneous hemorrhages (petechial) Prolongation of bleeding time 2) Vitamin K deficiency: Vitamin K: fat-soluble vitamin formed by intestinal bacterial flora Vitamin K → formation of factors II, VII, IX and X by liver. Causes of Deficiency: Absence of intestinal bacterial flora in newborn infants Obstruction of bile duct (as bile needed for absorption) Prolongation of clotting time 3) Hemophilia: Congenital sex-linked disease (carried on X chromosome). Recessive, carried by female to their males sons 3 types: Hemophilia A: absence of factor VIII (85%) Hemophilia B: IX (10%) Hemophilia C: XI (5%) Characterized by severe bleeding even after mild trauma Prolongation of clotting time. 16  Platelets (Thrombocytes) Small oval granulated, non-nucleated 300,000/mm3 ↓platelet number =thrombocytopenia. Formed in bone marrow diameter of platelets is about 2-4 µm Structure of Platelets A. Platelet Membrane: (Glycoprotein coat) Contain glycoprotein receptors for: collagen, von Willebrand factor (vWF), fibrinogen Contain phospholipid Form platelet factor 3 (PF3) →helps clotting Platelet activating factor (PAF)→activate phospholipase C Membrane forming (invagination)= open canalicular system: ↑surface area for uptake of calcium and release of intracellular substances. B. Platelet Cytoplasm: contain Beneath the membrane: Microtubules (skeleton), Contractile proteins (actin, myosin, thrombosthenin ) allow platelet to contract & change their shape Intracellular organelles: Golgi, endoplasmic reticulum, Mitochondria, Lysosome Glycogen for energy Enzymes for prostaglandins synthesis from phospholipids of platelet membrane. Prostaglandins are local hormones that mediate vascular and local tissue reactions. Granules: see before 17 18