DISEASES OF RBCs

1. DISEASES OF RBCs MAJI JOSE

2. DISORDERS OF RBC ANEMIA IRON DEFICENCY ANEMIA PLUMMR VINSON SYNDROME PERNICIOUS ANEMIA MEGALOBLASTIC ANEMIA APLASTIC ANEMIA SICKLE CELL ANEMIA THALASSEMIA ERYTHROBLASTOSIS FETALIS POLYCYTHEMIA

3. Normal range • 5.4 million/cu mm in males • 4.8 million/cu mm in females Pathological variation in number • Polycythemia- above 7mil/cu mm • Anemia- decreased

4. Variation in shape • Crenation Projections from the surface(Alkaline PH) • Spherocytosis Hereditary spherocytosis, autoimmune hemolytic anemia & ABO hemolytic disease of newborn. • Sickle cells or drepanocytes Sickle cell disease

5. Poikilocytosis • Schistocytosis Fragmentation of RBC Thalassemia, megaloblastic & Fe deficiency anemia, severe burns. • Leptocytosis Thinned RBC eg: target cells. Fe deficiency anemia, thalassemia. • Acanthocytosis Coarsely crenated RBC. Post splenectomy, chronic liver disease.

6. Burr cells • Cell fragments with >1 spines. • Uraemia. • Stomatocytes • Central slit like appearance. • Alcoholism.

8. Variation in structure • Punctatebasophilia • Basophilic granularity in RBC. • Aplastic anemia, thalassemia, myelodysplasia, infections & lead poisoning. • Howell jolly bodies • Purple nuclear remnants. • Megaloblastic anemia.

9. RBC Indices • RBC count Normal : 5.5 million/mm3 (males) 4.8 million/mm3 (females) • Hb Normal : 13-18g/dl (males) 11.5-16.5g/dl (females) • PCV Normal : 45ml/100ml

10. MCV Normal : 77-93 fl • MCH Normal : 27-32 pg • MCHC Normal : 27-32 g/dl

11. DISORDEROFRBC Anemia State in which the hemoglobin level in the blood is below the lower extreme of the normal range for the age & sex of the individual. PREVALENCE : F > M AGE : young age.

12. Etiological classification of anemia- wintrobe Loss of blood Acute post hemorrhagic anemia Chronic post hemorrhagic anemia. • Anaemia due to impaired red cell production • 1.Impaired blood production resulting from • Deficient haem synthesis - Fe def anemia • Deficient vitamins- vit B 12/folic acid. • 2.Inadequate production of mature erythrocytes • Defecency of erythroblast • - Atrophy of bone marrow: aplasia anemia. • -isolated erythoblastopenia. • Bone marrow infiltration • Leukemias • Lymphomas • Myelosclerosis • Multiple myeloma • endocrine abnormality • Myxedema • Addisionionadernalinsufficency • Thyroidism • chronic renal disease • chronic inflammatory disease • -infection • -Non infectious deasease • Cirrhosis of liver Anaemia • excessive distruction of RBC • extracorpuscular cause: • antibiotics • infection • Splenicdistruction • Drugs,chemicals • Truma of RBC • -intracorpuscular cause • Hereditary: • Disorder of glycolysis. • Abnormality in synthesis of globin. • Abnormal RBC membrane. • Erythropoiticprophyria. • Aquired : • Lead poisining

13. Excessive destruction of RBC Extracorpuscular cause: • antibiotics • infection • Splenicdistruction • Drugs,chemicals • Truma of RBC Intracorpuscular cause • Hereditary: • Disorder of glycolysis. • Abnormality in synthesis of globin. • Abnormal RBC membrane. • Erythropoiticprophyria. • Aquired : • Lead poisining

14. Anaemia due to impaired red cell production • 1.Impaired blood production resulting from • Deficient haem synthesis - Fe def anemia • Deficient vitamins- vit B 12/folic acid. • 2.Inadequate production of mature erythrocytes • Defecency of erythroblast • Atrophy of bone marrow: aplasia anemia. • isolated erythoblastopenia. • 3. Bone marrow infiltration • Leukemias • Lymphomas • Myelosclerosis • Multiple myeloma • 4. Endocrine abnormality • Myxedema • Addisionionadernalinsufficency • Thyroidism • - chronic renal disease • 5. chronic inflammatory disease • -infection • 6.Non infectious disease • Cirrhosis of liver

15. MORPHOLOGIC CLASSIFICATION • MACROCYTIC • Lack of erythrocyte maturing factors. • NORMOCYTIC • Hemorrhage, hemolysis, lack of blood formation & dilution of blood with fluid. • SIMPLE MICROCYTIC • Infections & inflammatory diseases. • HYPOCHROMIC MICROCYTIC • Fe deficiency.

16. CLINICAL FEATURE

17. IRON DEFECIENCY ANEMIA Most prevalent single deficiency state. Most prevalent anemia in Indians , females Etiology • Increased blood loss • Uterine – menstruation , post menopausal uterine bleeding, repeated miscarriages • Gastrointestinal – peptic ulcer, hookworm infestation, cancer, varices, ulcerative colitis, aspirin ingestion. • Renal tract – hematuria, haemoglobinuria • Nose – epistaxis

18. Increased requirement • Growth spurts( 1- 2.5mg /day) • Pregnancy & lactation( 1.5-2.5 mg/day) • Inadequate dietary intake • Poor economic status • Anorexia • Elderly individuals • Decreased absorption • Partial gastrectomy • Achlorhydria • Intestinal malabsorption

19. Clinical features • Mainly reported in females in 4th/5th decay of life • Lassitude, weakness, fatigue, • dyspnoea on exertion & palpitations • Lemon tinted pallor of skin & mucous membrane, conjunctiva . • Splenomegaly • Koilonychia and brittle nails. • Numbness and tingling of finger ,toes and bone pain.

20. Oral manifestations • Glossitis and stomatitis with atrophy of papillae(bald tongue). • Pallor of mucosa • Oral candidiasis, burning mouth, recurrent apthous ulcers, • angular cheilitis

21. Investigation • Blood examination -hypochromatic microcytic anemia. • Hb is low with RBC count 3,000,000 to4,000,000 cells/cu.mm • Bone marrow aspiration-reveals absence of stainable iron.

22. Biochemical findings – • Plasma ferritin- measure iron store and is a specific test. (150 – 2000ng /dl) • Plasma iron – low. (Serum iron level 80 – 180ug /dl) • Elevated total iron binding capacity (250 – 450 ug /dl) • Transferrin saturation < 16% is consistent finding • Increased soluble transferrin receptor.

23. Histological alterations: • Deficiency of keratinized cells. • Reduced cytoplasmic diameter of cells with paradoxical enlargement of nucleus. • Abnormal cellular maturation: Disturbed nuclear pattern, increase in nucleoli, double nuclei & karyorrhexis

24. DIAGNOSIS • Careful reasoned assessment of the cause. • Based on definitive investigation: serum ferritin level <30microgrm/l • bone marrow aspirates which fails to stain with perssian blue. indicated stored iron depletion.

25. ORAL HEALTH CONSIDERATION • Surgical procedure may result in bleeding and poor wound healing. • Hemorrhagic manipulation should be deferred for a minimum of 2wk. • Hb values below 10g pt is in risk for elective dental treatment and GA

26. MANAGEMENT - iron supplementation. - oral discomfort is managed by topical rinse with local anesthetics

27. PLUMMER – VINSON SYNDROME • SYNONYM: Paterson kelly syndrome / sideropenic dysplasia. • A rare syndrome with triad of dysphagia, iron deficiency anemia and upper esophageal web/strictures. • Age and sex: middle age women between 4th-7th decayed. • Etiology: iron deficiency anemia malnutrition autoimmune genetic disorders

28. CLINICAL FEATURES • Dysphagia: intermittent /progressive. • Weight loss • Symptoms of anemia • Splenomegaly • Carcinoma of upper alimentary tract also reported.

29. Oral manifestation • Cracked or fissured corner of mouth. • Painful tongue with atrophy of papillae • Esophageal webbing can be demonstrated radiographically

30. Oral health consideration • Physician consultation • Hb<8grms/dl GA is avoided MANAGEMENT • Same as iron deficiency anemia. • Early diagnosis and sooner treatment with iron supplements will resolve webs which are not substantially obstructive. • Follow up due to increase risk of carcinoma.

31. Megaloblastic anemia Results from deficiency of vit B12 + folic acid or due to disturbance in folic acid metabolism. Recommended Daily requirement of folic acid is 200ug Recommended Daily requirement of vit B 12 is 2 – 4ug.

32. ETIOLOGY • Vitamin B12 deficiency • -Inadequate dietary intake • -Malabsorption • Gastric – Pernicious anemia, • gastrectomy , lack of • intrinsic factor • Intestinal – Tropical sprue, • Crohn’s d/s, • tape worm • infestation • Folate deficiency • Inadequate dietary intake • Malabsorption – • In tropical sprue, Coeliac disease, • partial gastrectomy, • crohns d/s, Jejunal resection • Excess demand • -Physiologic: Pregnancy, lactation, • infancy • -Pathological: Malignancy, • Chronic exfoliative skin disorders, • tuberculosis, Rheumatoid arthritis • Excess urinary folate loss – • Inactive liver disease, • Congestive heart failure

33. CLINICAL FEATURES • 90% cases shows malaise • 80% cases shows paraesthesia • 50% cases shows breathlessness • 20% shows sore mouth. • Weight loss, poor memory, personality changes, depression, grey hairs, skin pigmentation, hallucination and visual disturbance.

34. ORAL MANIFESTATION • Smooth tongue and angular cheilitis. • Glossitis with initial swelling and redness of tip and lateral margins of tongue. • Filiform papillae is first to disappear and fungiform papillae remains as prominent spot, in advance state even that is lost.

35. Investigation and diagnosis • Hb : low • Erythrocyte count : low-leading to anemia • Blood picture : • oval macrocytosis, poikilocytosis, red cell fragmentation, basophilic stippling. • MCV > 110fL. • RBC appear hyperchromic but MCHC is normal

36. Bone marrow findings : • increased cellularity, megaloblastic changes in erythroid series. • Biochemical tests : • plasma LDH is increased • Rise in serum unconjugatedbilirubin both due to intramedullaryhemolysis. • Serum iron & ferritin – normal or elevated.

37. Specific tests for vitamin B12 deficiency: • Serum vit B12 assay. • Schilling test ( radioisotope absorption test) – distinguish & detect lack of IF & malabsorption. • Specific tests for folate deficiency: • Urinary excretion of FIGLU. • Serum folate assay. • Red cell folate assay.

38. oral health consideration Folatedeficency + alcoholism = bleeding due to inhibition of liver function therefore bleeding profile should be determined before surgical procedure.

39. Management • Oral folic acid 5mgs daily for 3wks – for acute deficiency. • Followed by 5mgs once weekly as maintenance therapy. • Prophylactic folic acid in pregnancy will prevent magaloblastosis in women with high risk.

40. Pernicious anemia • Synonyms:Addisonian anemia • First described by Addison in 1885. • Refers to anemia due to deficiency of vit B12 this occurs due to lack of production of IF in stomach. • Common Chronic hematological disorder with an incidence of 25/100,000 population over age of 40-60 yrs.

41. Etiology • Autoimmune – in which gastric mucosa is atrophic with loss of parietal cells causing deficiency of intrinsic factor. • Autosomal recessive form. • Associated with other autoimmune diseases like grave’s disease, myxoedema, diabetes etc. • Abnormal auto-antibodies : Anti parietal cell Ab(90%) Anti IF Ab (50%)

42. Oral changes (1st ) • Tongue : Glossopyrosis, Glossodynia,& • Glossitis • Hunter’sMoeller’sglossitis, • beefy red tongue. • Mucositis • Aphthous like ulcerations • Angular chelitis • Dysphagia • hematological • Macrocyticmegaloblastic • pancytopenia • Risk of myocardial infaction • Mild jaundice, diarrhoea • Purpura , melanin pigmentation • Weight loss, anorexia, premature • greying of hair, malabsorption Clinical features • Neurological • Peripheral neuropathy • Numbness, paraesthesia, weakness • Ataxia, poor finger coordination • Diminished reflexes • Dementia , depression, irritiblity,psychosis. • Folic acid def. • Neural tube defects, cleft lip & palate in fetus

43. INVESTIGATIONS • RBC count is decreased often to 100,000 or less /cubic mm. • Blood smear: • macrocytosis • characteristics pear shaped or tear drop erythrocytes • Howell jolly bodies - basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes • Cabot’s rings punctatebasophilia. Cabot rings are thin, red-violet  stained, threadlike strands in the shape of a loop or figure-8 that are found on rare occasions in erythrocytes

44. Hbcount of RBC is increased this is due to increase in size of RBC but MCHC is normal. • Co-existing iron deficiency anemia: D/D is reticulocyes response and improvement in hematocrit value after parental administration of cobalmine.

45. Biochemical findings: • Sensitive and screening test for pernicious anemia is schilling test.—radioactive cynocobalamine. • Increased serum bilirubin level. • Increased serum LDH • Increased serum iron & ferritin • Bone marrow biopsy: • erythroid precursors with large nucleus – checker board appearance

46. Diagnosis • Decreased plasma level of vit B12 by shilling test • Achlorhydria • Presence of serum antibiotics to intrinsic factor.

47. Oral health consideration • Any surgical treatment is deferred until anemia is controlled due to excessive bleeding.

48. Treatment • Hydroxycobalamine 1000microgm i.m. inj for initial 4-6wks --1000microgm /wk. life long. • Oral administration of 2000microg daily 1000microg /wkly with tapering dose . -Hb will rise every 10g/l every wk. -the reticulocyte count will peak by 5th-10th day -sensory neuropathy takes 6-12 mths to correct. -long standing neurological damage will not correct. Due to painful oral condition – diphenhydramine elixer- symptomatic.

49. APLASTIC ANEMIA • A rare blood dyscrasia mainly seen in developed countries with 2-4new cases/million population per annum. PATHOGENESIS Failure of pluripotent stem cells producing hypoplasia of bone marrow characterized by peripheral pancytopenia.(decreased RBCs, WBCs& Platelets)

50. ETIOLOGY & CLASSIFICATION PRIMARY APLASTIC ANEMIA • Fanconi’s anemia (congenital) • Immunologically mediated (acquired) SECONDARY APLASTIC ANEMIA Drugs : cytotoxic drug antibiotics –chloramphinacol, sulphonamides. antirheumatic agent. antithyroid drugs anticonvulsants Chemicals: benzene toludine blue solvent misuse. Insecticides-DDT Radiation Infections: Viral hepatitis, EBV, AIDS etc.