RBC

Red Blood Corpuscles / Cells

1. Seminar – 3 Presented by Dr. Nabeela Basha RBC

2. CONTENTS Introduction History General features Erythropoiesis Hemoglobin ESR & PCV RBC Disorders Public Health Significance Conclusion References Previous year questions

3. INTRODUCTION RBC - red cells / red blood corpuscles / haematids / erythroid cells / erythrocytes. Derived from Greek  erythros  for "red" and  kytos  for "hollow vessel", with  - cyte  translated as "cell" in modern usage. Non-nucleated formed elements in the blood. It lacks cytoplasmic organelles such as nucleolus, mitochondria & ribosomes . The red color of RBC is due to the presence of Hemoglobin (90%).

4. HISTORICAL BACKGROUND JAN SWAMMERDAM-1658 -   Dutch biologist and microscopist . He called them ruddy globules ANTON VAN LEEUWENHOEK-1674- Discovered Microscope and established its size. OTTO FUNKE 1851 - German physiologist was the first scientist to successfully crystallize hemoglobin. " Blutfarbstoff " DR. MAX PERUTZ- 1959 - by use of X-ray crystallography unravelled the structure of hemoglobin MENGHINI-1747- presence of iron in the blood, identified the red corpuscles as the chief site of iron within the organism.

5. GENERAL FEATURES Dimensions Normal Count Composition Functions Fragility Variations Fate & Lifespan

6. DIMENSIONS Shape: Biconcave Size: 7.2um in diameter Thickness: 2um at the periphery and 1um at the center Volume: 87um 3

7. Advantages of Biconcave Shape of RBCs: Greater surface area for exchange of gases. Flexibilty of RBC Minimal tension when the volume of cell alters. How is the shape maintained? Spectrin - a contractile protein - maintains shape and flexibility of RBC - Antigen on cell membrane – helps in blood group classification

8. NORMAL COUNT Adults males: 4.5 – 6 million cu mm of blood Adult females: 4 – 5.5 million cu mm of blood At birth: 6.7 million cu mm of blood

9. COMPOSITION 62.5% water 35% Hemoglobin 2.5% : - Sugar – glucose - Lipids – Cephalin , Cholesterol & Lecithin - Protein – Glutathion : insoluble protein which acts as a reducing agent and prevents damage of hemoglobin - Enzymes – Carbonic anhydrase and catalase - Ions – Na + , K + , Ca 2+ , PO 4 3-

10. FUNCTIONS Respiratory Acid Base balance Maintain viscosity Pigment: various pigments are derived from hemoglobin after disintegration of RBC.

11. FRAGILITY AND HEMOLYSIS Hemolysis - Breakdown of RBC and liberation of hemoglobin. Fragility - Susceptibility of RBC to hemolysis or tendency to break easily. There are 2 types: 1. Osmotic fragility- due to exposure to hypotonic saline. 2. Mechanical fragility- due to mechanical trauma

12. VARIATIONS Physiologic causes of increase count: Age Gender High altitude Exercise Temperature Meal Decrease in count: High barometric pressure, Pregnancy, sleep

13. Pathological variations: Increase: Polycythemia Decrease: Anaemia

14. VARIATIONS IN SHAPE Crenation : Shrinkage as in hypertonic solutions. Spherocytosis : Globular form as in hypotonic conditions. Elliptocytosis : elliptical shape Sickle cell: Crescent shape Poikilocytosis : Flask, hammer or any other unusual shape.

15. VARIATIONS IN SIZE Physiological conditions: RBC in venous blood slightly larger than those in arterial blood. Pathological conditions: 1. Microcytes – smaller cells 2. Macrocytes – larger cells 3. Anisocytes – cells of different sizes

16. LIFESPAN AND FATE OF RBC Lifespan – 120 days Site of destruction: Reticuloendothelial system

17. ERYTHROPOIESIS The process of origin, development and maturation of erythrocytes. Site of erythropoiesis : In fetal life: - Mesoblastic stage - Hepatic stage - Myeloid stage In newborns, children and adults

18. FIGURE 10.1: Stem cells. L = Lymphocyte, R = Red blood cell, N = Neutrophil , B = Basophil , E = Eosinophil, M = Monocyte, P = Platelet.

19. Factors necessary for erythropoiesis : 1. General factors: -Erythropoietin - Thyroxine -Vitamins 2. Maturation factors: -Vitamin B 12 ( Cyanocobalamin ) -Intrinsic factor of Castle -Folic acid

20. HEMOGLOBIN Hb is the iron containing coloring pigment of RBC. 95% dry weight of RBC; 30 – 34% wet weight. Molecular weight of Hb is 68,000 Normal value: -At birth: 25g/dl -From puberty: 14-16 g/dl -Adult males: 15g/dl -Adult females: 14.5g/dl

21. STRUCTURE OF HEMOGLOBIN Conjugated protein Protein part called Globin and iron containing pigment called heme . Heme part is called porphyrin and is formed by 4 pyrole rings Globin is made up of 4 polypeptide chains – 2 alpha and 2 beta chains.

22. Types of Hemoglobin: Normal: - Adult Hb - Fetal Hb Abnormal derivatives: - Carboxyhemoglobin - Methemoglobin - Sulfhemoglobin

23. ERYTHROCYTE SEDIMENTATION RATE Red cells have the property of Rouleaux (piling one on the other) formation. Piled red cells are heavier than the individual ones. The rate at which the red cells fall is known as ESR. Normal values: Wintrobe’s method: Males: 0 – 9mm/hr Females: 0 – 20mm/hr Westergren’s method: Males: 3 – 7mm/hr Females: 5 – 9 mm/hr

24. Westergren’s method: Westergren’s tube is used which is 300 mm long & opened at both the ends. It requires collecting 2 ml of venous blood into a tube containing 0 .5 ml of sodium citrate. It should be stored no longer than 2 hours at room temperature or 6 hours at 4 °C. The blood is drawn into the tube to the 200 mm mark. The tube is placed in a rack in a strictly vertical position for 1 hour at room temperature,

25. Wintrobe’s method: The Wintrobe method is performed similarly except that the Wintrobe tube is smaller in diameter than the Westergren tube and only 100 mm long. EDTA anticoagulated blood without extra diluent is drawn into the tube, and the rate of fall of red blood cells is measured in millimeters after 1 hour. 

26. PACKED CELL VOLUME Hematocrit is the fractional volume of blood that the erythrocytes occupy It is a reliable index of red cell population. Normal values : Males – 46% Females – 42%

27. RBC INDICES MCV (MEAN CORPUSCULAR VOLUME ) The average volume of single RBC PCV per 100ml blood MCV =  10um 3 RBC count (million/cu mm) Normal range : 78 – 94 um 3 RBC with normal volume are called Normocytes RBC with less then normal volume, Microcytes RBC with more than normal volume, Macrocytes

28. MCH (mean corpuscular hemoglobin) The average content of Hb in average RBC. Hb in gm% MCH =  10pg RBC count (million/cu mm) Normal range: 28 – 32pg

29. MCHC (mean corpuscular hemoglobin concentration) Express the average concentration of hemoglobin per unit volume of RBC. It defined as the ratio of the weight of hemoglobin to volume of RBC. Hb in gm% MCHC =  100 PCV per 100ml blood Normal range: 33 – 38 gm/100ml of cells

30. DISORDERS OF RBC Anemia Morphologic classification Etiologic classification Polycythemia Polycythemia Vera Relative polycythemia Secondary polycythemia

31. ANEMIA Anemia is defined as Hb concentration in blood below the lower limit of the normal range for the age and sex of the individual. In adults, the lower extreme of normal Hb is taken as 13g/dl for males and 11.5g/dl for females.

32. MORPHOLOGICAL CLASSIFICATION Depends upon the size and color of RBC. Size of RBC is determined by mean corpuscular volume (MCV). Color is determined by mean corpuscular hemoglobin concentration (MCHC). By this method, the anemia is classified into four types

33. Hyperchromic Hypochromic Macrocytic Microcytic

34. ETIOLOGICAL CLASSIFICATION On the basis of etiology , anemia is divided into five types: 1. Hemorrhagic anemia 2. Hemolytic anemia 3. Nutrition deficiency anemia 4. Aplastic anemia 5. Anemia of chronic diseases.

35. IRON DEFICIENCY ANEMIA Iron deficiency anemia is the most common type of anemia . It develops due to inadequate availability of iron for hemoglobin synthesis. RBCs are microcytic and hypochromic .

36. Causes of iron deficiency anemia : i . Loss of blood ii. Decreased intake of iron iii. Poor absorption of iron from intestine iv. Increased demand for iron in conditions like growth and pregnancy. Features of iron deficiency anemia : Brittle nails, Spoon shaped nails (koilonychias), Brittle hair, Atrophy of papilla in tongue Dysphagia (difficulty in swallowing).

37. Oral manifestations: Pallor of mucosa Atrophy of oral mucosa Tongue changes – redness, soreness or burning sensation. Papillae of the anterior two thirds undergo atrophy. Angular cheilitis Ulcerations Slow healing

38. Diagnosis: Clinical – Koilonychia , angular cheilitis , depapillation of tongue Lab diagnosis – Hb level as low as 4g/100ml. MCV, MCH & MCHC all are reduced. RBC count slightly reduced or normal. Management: Iron supplement: oral ferrous fumerate or ferrous sulphate 300mg three to four times a day for a period of 6 months Parenteral route : single dose of iron sorbitol 1.5mg/kg body weight daily

39. Oral Health Considerations: For dental patients with extremely low Hb levels- physician consultation When Hb is less than 8g/dl, GA should be avoided Narcotic use should be limited for those with sever anemia as there is increased rick of ischemic heart disease.

40. PLUMMER VINSON SYNDROME Patterson Brown Kelly syndrome / Sideropenic dysphagia Characterized by iron deficiency anemia, dysphagia and esophageal webs or strictures. Clinical Features: Middle aged women- 4 th to 7 th decade of life Dysphagia , angular cheilitis , sore tongue. Patient complains of spasm in throat or food sticking in throat. Spoon shaped nails.

41. Management: Correction of anemia Dilation of esophagus – to correct dysphagia

42. SICKLE CELL ANEMIA First described by Herrick in 1910. Severe genetic disorder of hemoglobin synthesis. Autosomal dominant Abnormal hemoglobin, which under low oxygen tension, results in sickling of the cell. In this, α - chains are normal and β - chains are abnormal.

43. Diagnosis: Newborn screening is an important starting point for simple public health strategies such as parental education, penicillin prophylaxis, immunization and utilization of prenatal testing. The HbS solubility test ( Sickledex ) can be performed in 5mins for screening of adult hemoglobinopathies . Prenatal testing by DNA analysis of amniotic fluid at 14 to 16 weeks can be done to find out alterations and mutations in genes.

44. Clinical Features: Periods of latency interrupted by periods of acute crisis. Known sequelae include: Invasive infections Acute chest syndrome Strokes Severe anemia Chronic leg ulcers Hematuria Aseptic osteonecrosis

45. Oral Manifestations : Enamel hypomineralization Increased overjet and overbite Calcified canals Pallor of oral mucosa and delayed eruption of teeth. SCA is not associated with increased levels of gingivitis or periodontitis.* * Periodontal Disease in Sickle Cell Disease Subjects by John M. Crawford. Journal of Periodontology . March 1988, Vol. 59, No. 3, Pages 164-169

46. Management: Regular monitoring of hematological state Blood transfusion – cerebrovascular symptoms in early childhood , recurrent pulmonary thrombosis Mild to moderate anemia - Blood transfusion Risk of HIV and HEPATITIS infection – transfused patient Painful crisis – analgesics Incidence of hypoxia and dehydration should be avoided

47. Dental management Dental treatment - Directed towards palliative therapy during crisis period Preventive dental care – antiseptic mouth rinses , topical fluoride recommended Antibiotic prophylaxis – penicillin is the drug of choice Odontogenic and nonodontogenic infection should be aggressively treated Periodontal status - closely monitored

48. THALASSEMIA Thalassemia is an inherited disorder, characterized by abnormal hemoglobin . It is also known as Cooley’s anemia or Mediterranean anemia . It is more common in Thailand and to some extent in Mediterranean countries. Thalassemia is of two types: α - thalassemia β - thalassemia .

49. In normal hemoglobin , number of α and β polypeptide chains is equal. In thalassemia , the production of these chains become imbalanced because of defective synthesis of globin genes. This causes the precipitation of the polypeptide chains in the immature RBCs, leading to disturbance in erythropoiesis .

50. α- Thalassemia α - thalassemia occurs in fetal life or infancy. In this α - chains are less, absent or abnormal. In adults, β-chains are in excess and in children, γ-chains are in excess. This leads to defective erythropoiesis and hemolysis . The infants may be stillborn or may die immediately after birth.

51. β- Thalassemia More common type of thalassemia . In β - thalassemia , β - chains are less in number, absent or abnormal with an excess of α-chains. Severity ranges from complete lack of symptoms to transfusion dependence. Cooley’s anemia , or thalassemia major is the name for the most severe form.

52. Oral Manifestations: Excessive overgrowth of maxilla Oral mucosa has a lemon yellow tint because of chronic jaundice – hard palate and floor of the mouth. Chipmunk facies - Saddle nose, prominent malar bone, retracted upper lip Poor healing Spacing between teeth Discoloration of dentin

53. General management Blood transfusion Iron chelating agents – desferroxamine Folic acid supplements Splenectomy – severe cases

54. Dental management Poor wound healing after any surgical procedure Surgery has been used successfully to treat the facial deformities HIV and HEPATITIS infections are common in transfused patients Prophylactic antibiotics in splenectomy cases

55. MEGALOBLASTIC (PERNICIOUS) ANEMIA & VIT B12 (COBALAMIN) ANEMIA Occurs due to deficiency of Vit B 12 or folic acid or both, resulting in disordered cell proliferation. Clinical Features & Oral Manifestations: Weakness, anemia, palpitations, diarrhoea Paresthesia of finger, toes & also dementia may be observed. Burning sensation of tongue, angular cheilitis Hunter’s glossitis : Atrophy of filiform and fungiform papillae leading to smooth fiery red surface of tongue

56. Management: Blood tranfusion : when Hb level is less than 4g/dl of blood Folic acid supplements : initial dose - 5 mg orally daily maintenance dose - 5 mg orally once a week Vit B 12 therapy : Initial dose – 1000 mcg , intramuscularly 4 to 6 wks Maintenance dose – 1000 mcg intramuscularly once every week

57. APLASTIC ANEMIA A rare disorder characterized by peripheral blood pancytopenia associated with bone marrow suppression. Occurs due to failure of haematopoietic precursor cells in bone marrow to produce adequate number of all blood cell types.

58. Clinical Features: Commonly seen in young adults Erythrocyte deficiency : Headaches, pale skin, breathlessness Thrombocyte deficiency : Bruising & bleeding. Cerebral haemorrhages Leukocyte deficiency : Bacterial and fungal infections are common. Ankle edema, anginal pain, congestive cardiac failure

59. Management: Supportive therapy: Antibiotics & transfusion Bone marrow transplantation Stimulation of haemopoiesis and promote marrow recovery Androgenic steroids - oxymetholone Corticosteroids – Prednisolone or methyl prednisolone Antithymocyte or antilymphocyte globulin combined with cyclosporine.

60. POLYCYTHEMIA Abnormal increase in the number of RBCs in the peripheral blood, usually with increase in Hb level. Types: Polycythemia Vera Relative Polycythemia Secondary Polycythemia

61. POLYCYTHEMIA VERA Polycythemia rubra vera / Osler’s disease / Erythremia / Vaquez’s disease Uncontrolled proliferation of erythroid stem cells leading to excess of erythroid cell mass in the body. Clinical Features: Male predilection – Middle age Skin appears flushed, reddened Spleen is palpable

62. Tip of the finger has cyanotic appearance. Erythromealgia : Burning sensation with erythema and warmth in hand and feet. Dizziness and blackouts Oral manifestations: Purplish red discoloration of mucosa Swollen bleeding gingiva Petechiae

63. Management: Venesection : done at periodic intervals to remove 500-600ml of blood. Also called Phlebotomy. Radioactive phosphorus: Excellent treatment modality when the diagnosis is certain. Aspirin – given for thrombotic event

64. PUBLIC HEALTH SCENARIO Globally, anaemia affects 1.62 billion people, which corresponds to 24.8% of the population. The highest prevalence is in preschool-age children (47.4%), and the lowest prevalence is in men (12.7%). However, the population group with the greatest number of individuals affected is pregnant women (41.8%). In women, anaemia may become the underlying cause of maternal mortality and perinatal mortality.

65. Nearly 50 per cent of women of reproductive age and 26 per cent of men in the age group of 15-59 years are anemic. Nine out of ten anemia sufferers live in developing countries, about 2 billion people suffer from anemia and an even larger number of people present iron deficiency.

66. Anemia in India Infants, Pre-school Children, Adolescents and Women of Childbearing age, particularly Pregnant Women, are at greatest risk of developing Iron Deficiency Anaemia. The condition has a prevalence rate of 74 percent among pregnant women in the region ranging from 13.4 percent in Thailand to 87 percent in India. According to the NFHS-(III), more than half of women in India (55%) have anaemia, including 39 % with mild anemia, 15 % with moderate anemia and 2 percent with severe anaemia.

67. The survey further revealed that among the states, Assam is the worst affected with 72% of married women being anaemic , followed by Haryana (69.7%) and Jharkhand (68.4%). *Anaemia ‘a silent killer’ among women in India: Present scenario Kawaljit Kaur . Euro J Zool Res, 2014, 3 (1):32-36

68. Various health programmes : The National Nutritional Anemia Prophylaxis Programme (NNAPP) was launched in 1972 during the 4th five year plan in India with the aim to curb the prevalence of anemia. One of the largest nutritional supplement programmes , the Integrated Child Development Services (ICDS) scheme was initiated in 1975 in India to provide nutritious food to pregnant women and children.

69. Further, in 1991, the Government of India introduced policies to control nutritional anemia through promotion of iron rich food (green leafy vegetables: mustard leaves, bengal gram leaves, clocasia leaves etc., shepu or sowa , cereals: wheats , ragi , jawar ,, pulses: sprouted pulses, and jaggery ), provision of iron and folate supplements to high risk groups (all pregnant and lactating women, Intra-Uterine Device (IUD) users, and children between 1-5 years), and identification and treatment to severely anemic people.

70. National Rural Health Mission (NRHM), 2005, undertakes programme once in a month in villages to educate mothers on health and nutrition. In spite of the fact that the Health and Family Welfare Department in India has policies to provide iron supplement to pregnant women to prevent maternal anemia, evaluation from large scale programmes shows that maternal anemia has not declined significantly.

71. Some plausible reasons are the side effects of the iron pills and also improper utilization of health service and personal beliefs (Fox, 1983; Galloway and Mcguire , 1994). Prevalence of Iron-Deficiency Anaemia in India: Results from a Large Nationwide Survey by Ramesh Chellan . Lopamudra Paul. JOURNAL OF POPULATION AND SOCIAL STUDIES Volume 19 Number 1 July 2010

72. CONCLUSION Red blood cells play an important role in our health by carrying fresh oxygen throughout the body. Hemoglobin is the protein inside red blood cells that carries oxygen. Most people don't think about their red blood cells unless they have a disease that affects these cells. Problems with red blood cells can be caused by illnesses or a lack of iron or vitamins in the diet. Some diseases of the red blood cells are inherited.

73. Anemia is the most common disorder of the blood with it affecting about a quarter of people globally. Anemia goes undetected in many people, and symptoms can be minor or vague. Appropriate dental care improves a patient’s quality of life by preventing eating difficulties, oral diseases, and esthetic concerns, and facilitates the management of the disease by the hematologist .

74. Preventive dental care is must for patients with blood cell disorders of any kind in combinations with appropriate lab investigations and diagnosis before planning of any treatment.

75. REFERENCES Essentials of medical physiology by D r.Sembulingam . Medical physiology for dental students by Dr G K Pal Essential Pathology for dental students by Harsh Mohan 3 rd edn Text book of Oral Medicine Ghom 2 nd edn Human physiology for B.D.S by Prof. A K Jain 3 rd edn Burket’s Oral Medicine by Greenberg . Glick . Ship . 11 th edn

76. PREVIOUS YEAR QUESTIONS SHORT ESSAYS: RBC (10mks) (MDS Degree examinations March 1994, 2000) RBC Morphology & Functions (10mks) (MDS Degree examination April/May 07 & 2010) Iron deficiency anemia (10mks) (MDS Degree examination Sept 2007)