Blood - Composition, functions, applied aspects

Blood is a fluid connective tissue that plays a major role in transportation of various substances, maintains body temperature, blood pressure, fluid volume & composition, and acid-base balance.

Understanding the composition & parameters of blood is essential for a dental practitioner, since dental surgery involves various invasive procedures

A thorough clinical history of the patient, along with relevant haematological tests are essential before initiating complex surgical procedures in the oral cavity. Hence, understanding the various parameters of blood is necessary.

1. Blood Dr. Sangaragomathy A M I MDS Dept. of Public Health Dentistry KLES Institute of Dental Sciences, Bangalore

2. Contents Introduction Composition of Blood Plasma proteins Haemoglobin RBC WBC Platelets Blood grouping & Blood transfusion Blood parameters Conclusion References

3. Introduction Definition Characteristics Functions

4. Definition “ Blood is a Fluid connective tissue which transports substances from one part of the body to another” It provides nutrients & hormones to the tissues and removes waste products. It is confined in the CVS & constitutes a major part of ECF

5. characteristics Colour is opaque red due to pigment Haemoglobin in RBC Volume is 5-6 L (8% of body weight or 80ml/kg body weight) Viscosity is 5x more than water Specific gravity is 1.050 – 1.060 pH is 7.38 – 7.42 (alkaline)

6. functions Respiratory – Transports lungs → tissues) & tissues → lungs) Nutritive – Transport of glucose, amino acids, electrolytes, etc. tissues) Excretory – Transport of metabolic wastes to excretory organs (Kidneys, skin, intestine, lungs) Transport of hormones → target tissues) Protective – Defence mechanism (WBCs) Homeostatic – water & electrolyte balance, pH balance Maintenance of body temperature – distribution of heat from deeper organs to skin & lungs for dissipation, Latent heat of evaporation of blood Storage – Readymade source of glucose, water, proteins, electrolytes for emergency conditions like starvation, fluid loss, etc.  

7. Composition of blood

8. Composition of blood

9. What is Serum? Blood without clotting factors (II,V, VIII) & Fibrinogen If blood is allowed to clot in a test tube, then clots retracts & gives out serum.

10. Blood Plasma (55%) Formed Elements (45%) Water (91%) Solids (9%) Organic molecules(8%) Inorganic molecules (1%) ( 1%) NPN :Urea, Uric acid, Creatine, Creatinine, Xanthine, Hypoxanthine + Other Substances Glucose, cholesterol, triglycerides, Phospholipids, Hormones, enzymes, antibodies Plasma proteins (7%)

11. Plasma proteins Classification Functions Disorders

12. Plasma proteins: Classification Plasma proteins (7.4 g%) Albumin (4.8 g%) Globulin (2.3 g%) Alpha 1 globulin Alpha 2 globulin Beta globulin Gamma globulin Fibrinogen (0.3g%) Prothrombin A/G ratio = 2:1, indicator of liver/kidney disease plasma proteins

13. Plasma proteins: Functions Exert colloidal osmotic pressure (25mm Hg), important for maintaining fluid-electrolyte balance Contributes to blood viscosity – Fibrinogen & albumin are major contributors, maintain BP by providing resistance Coagulation of blood – Fibrinogen, Prothrombin, other clotting factors Defence mechanism – gamma globulins, antibodies Acid-base balance – due to its amphoteric nature combine with acids & bases, providing buffering action. plasma proteins

14. Plasma proteins : Functions Transport – combine easily with many substances & provide transport Role as reserve proteins Provide suspension stability – by virtue of which RBCs remain uniformly suspended in blood, (mainly due to Globulin & Fibrinogen) Fibrinolytic Function – enzymes of fibrinolytic system digest intravascular clot (thrombus) to prevent thrombosis Genetic information – many plasma proteins show polymorphism, serve as valuable tool in population genetics. plasma proteins

15. Plasma protein : Disorders Physiological variations Infants : total protein levels ↓ due to gamma globulins ↓ Old age: tendency for albumin level ↓ & globulin ↑ Pregnancy : during 1 st 6 months, albumin & globulin ↑ & fibrinogen ↓ Hypoproteinaemia Causes Dietary deficiency Malabsorption syndrome Liver disease Kidney disease Haemorrhage & extensive burns Effects ↓ colloidal osmotic pressure – resulting in water retention plasma proteins

16. Plasma protein : Disorders Hyperproteinaemia Causes Acute inflammatory conditions (acute phase proteins like: C-reactive proteins ↑) Acute tissue destruction (MI, acute phase proteins ↑) Chronic inflammation & malignancies (C-reactive proteins ↑) Multiple myeloma ( Bence Jones proteins ↑) , due to abnormal formation in bone marrow Reversal of normal A/G ratio Albumin synthesis ↓ in liver diseases, while globulin remains normal (synthesised by B lymphocytes) Globulin levels ↑ in hyperproteinaemia cases plasma proteins

17. haemoglobin Structure Variations Disorders

18. Structure of haemoglobin 1 molecule of Hb has 4 Haem groups, each attached to one of the 4 polypeptide chains of Globulin Haem - Iron-Porphyrin complex Porphyrin nucleus (tetra-pyrrole rings) Iron ( form, attached to atom of each pyrrole ring) Globulin – 4 polypeptide chains 2 ∝ chains 2 β chains (adult Hb) On a bond is available for loose union (oxyhaemoglobin & deoxyhaemoglobin, since there are 4 haem units, 1Hb can carry 4 molecules of  

19. Variations of haemoglobin Physiological variations Adult Hb HbA – ( Hb - ( minor component in normal adults (2.5%) Foetal Hb (HbF) Disappears 2-3 months after birth Has more affinity for oxygen than HbA  

20. haemoglobinopathies Sickle Cell Anaemia Autosomal Recessive trait (HbS) due to substitution of valine instead of glutamic acid at 6 th position of β chain of HbA. At ↓ tension , HbS precipitates into crystals within RBCs – that elongate & changes shape of RBCs from biconcave to sickle shaped Sickle cells are less flexible , cause blockade of microcirculation, decreasing blood flow. They are more fragile & liable to haemolysis – producing sickle cell anaemia Treatment : Drugs (5-azacytidine, hydroxyurea) Bone marrow transplantation  

21. Thalassemia Autosomal recessive trait Resulting in defective synthesis of polypeptide chains of HbA

22. Medical Management Blood Transfusion, gene therapy, drugs (hydroxyurea), Hematopoietic stem cell transplantation  (HSCT)  Dental Considerations Thorough history must be taken, medical diagnosis of specific type of thalassemia is necessary – treatment plan differs based on the type Complex surgeries considered only in less severe cases Treatments not indicated in Thalassemia major Liver tests & coagulation tests must be carried out before treatment Antibiotic prophylaxis before & after treatment

23. rbc Morphology Erythropoiesis Variation in counts Anaemia

24. RBC Morphology Normal shape : Biconcave disc Normal Count: At birth: 6-7 million/mm3 Adult males: 5-6.5 million/mm3 Adult females: 4.5 – 5.5 million/mm3

25. haemopoiesis Sites Yolk sac (1 - 2 months of gestation) Liver & spleen (3 rd month of gestation) Bone marrow (7 th month onwards) Precursors Pluri/multipotent stem cells Lymphoid progenitors Myeloid progenitors Granulocyte-monocyte progenitors Erythroid progenitors Megakaryocyte progenitors

26. erythropoiesis RBCs develop from BFU-E & CFU-E derived from committed progenitor cells. It takes 7 days for formation 7 maturation of RBCs. 5days till the stage of reticulocytes 2 days for maturation Reticulocytes spend 1-2 days in marrow, circulates for 1-2 days in peripheral blood, then matures in spleen. Lifespan of RBC = 120 days

27. Regulation of erythropoiesis Erythropoietin (juxta-glomerular apparatus of kidneys) Vitamin B12 & Intrinsic factor Folic acid

28. Variations in count Physiological Increase Age : At birth its more Sex: females< males High altitude Excessive exercise Emotional conditions like anxiety After meals Physiological Decrease Pregnancy At high barometric pressure After sleep Pathological conditions Anaemia (reduced RBC count or Hb level or both) Polycythaemia (> 7 million/mm3) Primary (P. vera): malignant bone marrow Secondary : chronic hypoxia

29. anaemia Hb level less than 13g/dl in females 11.5 g/dl in males 15g/dl in newborn 9.5 g/dl at 3 months of age RBC count < 4 million/mm3 Grading Mild (8-10 g/dl) Moderate (6- 8 g/dl) Severe (<6 g/dl) Clinical Features Generalised weakness Pallor Breathlessness Palpitations Visual disturbances Menstrual disturbances Anorexia Atrophy of papillae of tongue

30. anaemia Classification Deficiency Iron deficiency Megaloblastic (folic acid deficiency) Pernicious (b12 deficiency) Protein & vitamin C deficiency Blood loss Acute & Chronic post-haemorrhagic anaemia Aplastic anaemia Haemolytic anaemia Anaemia due to chronic diseases

31. Iron deficiency anaemia Causes Inadequate intake of iron (anorexia, old age, poor economic background) Increased loss of iron (blood loss; uterine bleeding, GI bleeding) Increased demand of Iron (Infancy, childhood, pregnancy, menstruation) Decreased absorption (gastrectomy, intestinal malabsorption diseases) C/F Koilonychia (spoon shaped nails) Atrophic glossitis Angular stomatitis Plummer-Vinson syndrome

32. Iron deficiency anaemia

33. Iron deficiency anaemia L/F Blood picture : MCV, MCH, MCHC decreased Bone marrow: Erythroid hyperplasia, Deficient marrow iron Biochemical: TIBC decreased, Serum iron & serum ferritin decreased Treatment Oral administration of iron salts Correction of causative factor

34. Megaloblastic anaemia Causes Inadequate intake of B12 Malabsorption of B12 Gastric causes Autoimmune disease, lack of IF (Addisonian pernicious anaemia) congenital lack of IF Gastrectomy Intestinal causes Crohn’s disease Ileal resection Tapeworm Folate deficiency Malabsorption Pregnancy, lactation Malignancies Drugs (OCP, methotrexate) L/F Macrocytosis (MCV & MCH increases) Reticulocytosis Nucleated RBCs Serum folate, b12 levels decreased Serum iron & ferritin increased Serum bilirubin increased Treatment Dietary supplements Addressing the cause

35. wbc Leukopoiesis Functions Disorders

36. LEUCOPOIESIS Granulocytes – formed & stored in bone marrow, within 12 days Lymphocyte precursors migrate from bone marrow to thymus & lymphoid tissues to mature and develop into lymphocytes Regulation Cytokines G-CSF M-CSF IL-1, IL-3 Prostaglandins

37. functions Phagocytosis Margination, Emigration & diapedesis, Chemotaxis, Opsonization, Engulfment, Secretion, Degradation Reaction to inflammation (release of PG, LT, thromboxane) Febrile response (endogenous pyrogens)

38. disorders Neutrophilia (>10,000 /mm3) Physiological Newborns Exercise Menstruation, Pregnancy, lactation Pathological Infections Gout, rheumatoid fever Burns, MI Neutropenia (< 2,500 /mm3) Typhoid Malaria Aplasia of bone marrow Bone marrow depression Cytotoxic drugs X-ray Arsenic poisoning

39. disorders Eosinophilia (>500 /mm3) Allergy Parasite Scarlet fever Eosinopenia (< 50 /mm3) Steroids Stress Acute pyogenic infections Basophilia (>100 /mm3) Viral Allergy CML Basopenia Steroids Drugs Acute pyogenic infections

40. disorders Monocytosis (>800 /mm3) Bacterial, viral, protozoal infections Monocytopenia (rare) Hypoplastic bone marrow Leukemia AML ALL CML CLL Lymphocytosis (>4000 /mm3) Physiological Newborns Menstruation Pathological TB Viral infections Autoimmune diseases Lymphatic leukemia Lymphopenia (<1500/mm3) Steroids, irradiation, AIDS

41. platelets Thrombopoiesis

42. thrombopoeisis

43. Blood groups & blood transfusion

44. Blood grouping

45. Compatibility

46. Haemolytic disease of newborn Occurs as a result of incompatibility of Rh blood groups between mother & foetus MOA: Entrance of Rh + ve foetal RBC into Rh- ve mother’s circulation during 1 st pregnancy Production of Rh antibodies in mother Rh incompatibility reaction in 2 nd pregnancy

47. Haemolytic disease of newborn Manifestations Erythroblastosis fetalis (Erythroblasts increase, excessive haemolysis, death due to severe anaemia) Icterus gravis neonatorum (Jaundice, hepato-splenomegaly) Kernicterus (neurological syndrome, bilirubin affects basal ganglia, causing motor disturbances) Hydrops fetalis (haemolysis, oedema, premature birth or infant death) Prevention Injection of single dose Rh antibodies soon after child birth Treatment Replacement of baby’s Rh+ve blood with Rh – ve blood, exchange transfusion

48. Blood transfusion Indications Blood loss Quick restoration of haemoglobin Exchange transfusion Blood diseases Acute poisoning Precautions Absolute indication Crossmatching Screening of donor’s blood Proper aseptic conditions Transfusion at slow rate Careful watch on recipient's condition Crossmatching Major cross-matching : mixing of donor’s cells with recipient's plasma Minor cross-matching : mixing of recipient’s cells with donor’s plasma

49. Blood parameters RBC indices Bleeding indices

50. RBC Indices Packed Cell Volume (PCV) AKA Haematocrit value Refers to the percentage of cellular elements Males : 45%, Females : 42% Increased: Polycythaemia Decreased : Anaemia RBC Indices MCV MCH MCHC

51. RBC Indices MCV – Mean Corpuscular Volume

52. RBC Indices MCH – Mean Cell Haemoglobin Normal : 30 pg Increased : Megaloblastic anemia

53. RBC Indices MCHC – Mean Cell Haemoglobin Concentration

54. RBC Indices MCHC – Mean Cell Haemoglobin Concentration

55. bleeding Indices BT (Bleeding Time) Time lapse between skin prick & arrest of bleeding. 1-6 minutes Prolonged in purpura, normal in haemophilia CT (Clotting Time) Time taken by fresh blood to get coagulated. 4- 10 minutes Prolonged in haemophilia, Christmas disease, Vitamin K deficiency, Disseminated Intravascular Coagulation

56. bleeding Indices PT (Prothrombin Time) 10- 14 seconds (PT) – along with its derived measures, prothrombin ratio (PR) & international normalized ratio (INR) – is an assay for evaluating the extrinsic pathway & common pathway of coagulation. Used to determine clotting tendency of blood, such as measure of warfarin dosage, liver damage & vitamin K status. PT measures the following coagulation factors: I (fibrinogen), II (prothrombin), V (proaccelerin), VII (proconvertin), and X (Stuart–Prowers factor). PT is often used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway and common pathway of coagulation. Normal aPTT : 30-40 seconds

57. conclusion Blood is a fluid connective tissue that plays a major role in transportation of various substances, maintains body temperature, blood pressure, fluid volume & composition, and acid-base balance. Understanding the composition & parameters of blood is essential for a dental practitioner, since dental surgery involves various invasive procedures A thorough clinical history of the patient, along with relevant haematological tests are essential before initiating complex surgical procedures in the oral cavity. Hence, understanding the various parameters of blood is necessary.

58. references Textbook of HUMAN PHYSIOLOGY for Dental Students by Indu Khurana Human Physiology for BDS, 5 th edition, by A K Jain https://www.semanticscholar.org/paper/Alpha-and-beta-thalassemia.-Muncie-Campbell/b6a4d364e68834f9574213805ef9d96bafbd328e/figure/1