blood

1. BLOOD

2. CONTENTS
• INTRODUCTION
• FUNCTIONS
• COMPOSITION
• PLASMA AND PLASMA PROTEINS
• HEMATOPOIESIS
• ERYTHROCYTE
• HEMOGLOBIN

3. • BLOOD INDICES
• ANEMIAS
• POLYCYTHEMIA
• HEMOGLOBINOPATHIES
• CLINICAL CONSIDERATIONS
• DENTAL CONSIDERATIONS
• BLOOD GROUPING
• BLOOD TRANSFUSION.

4. INTRODUCTION
• Blood is type of specialised connective tissue.
• CHARACTERISTIC PROPERTIES :
– COLOUR- OPAQUE, RED, ART- SCARLERT, VEN – PURPLE RED.
– VOLUME-
– ALKALINE – PH IS 7.4
– SPECIFIC GRAVITY- 1.052-1.061
– VISCOSITY – 5 TIMES THAN WATER

5. FUNCTIONS
• Respiratory – TRANSPORT of gases
• Nutritional – glucose, AA, LIPIDS AND VIT.
• Excretory - KIDNEY SKIN LIVER
• Transport of hormones and enzymes
• Homeostatic processes
• Defensive function.

6. Composition

7. PLASMA
• Is a pale yellow, colloidal solution.
• Normal plasma volume = 3 L
• Contains : water – 92%
solids – 8 to 9%
• SERUM = PLASMA – FIBRIN

8. COMPOSITION OF PLASMA
• ORGANIC SUBSTANCES:
1. Proteins, Carbohydrates(glu) and Fats(neutal fats,phlipid,chol.)
2. Amino acids
3. Non protein nitrogenous substances - ammonia, urea, etc.
4. Internal secretions like hormones.
5. Enzymes - Amylase, Carbonic anhydrase, Alkaline phosphatase,
Acid phosphatase, lipase, esterase.
6. Antibodies

9. • Inorganic substances: Na, k , ca , mg, cl, i.
• Gases : o2 and co2
• Blood levels of some important substances:
GLUCOSE = 100 – 120 gm %
CHOLESTEROL = 150 – 250 mg %
BILIRUBIN = 0.5 – 1.5 mg %
CALCIUM = 9 – 11 mg %
IRON = 50 – 150 mg %

10. Plasma proteins
• Total proteins : 7.4 gm%
• Serum albumin: 4.7 gm% - 69,000
• Serum globulin: 2.3 gm% -1,56,000
• Fibrinogen: 0.3 gm% - 4,00,000
• Properties :
1. Molecular weight -
2. Colloidal Osmotic pressure – 25mm Hg. ( albumin)
3. Specific gravity – 1.026
4. Buffer action – 1/6 of total buffering action of blood.

11. FUNCTIONS
1. Coagulation of blood.
2. Defense mechanism
3. Osmotic pressure
4. Role in ESR.
5. Suspension stability of RBC- GLOBULIN AND FIBRINOGEN
6. Reserve proteins

12. • Variations in levels: albumin and globulin in opposite
• Hypoproteinemia :
– Hemorrhage
– Extensive burns
– Cirrhosis
– Chronic infections
• Hyperproteinemia :
– Dehydration
– Acute hepatitis/nephritis

13. HEMATOPOIESIS
• Starts in 3rd week of intrauterine life.
• Blood forming tissues
A. myeloid – rbc, granulocyte, monocytes, platelets
B. Lymphoid – lymph nodes, thymus, spleen
• Myeloid : erythroid ratio = 3:1

14. Sites of haematopoiesis
• In embryo :
I. Mesoblastic stage: first 2 months, mesenchyme of yolk sac.
II. Hepatic stage: 3rd month.liver , spleen, ltmphoid organs.
III. Myeloid stage: red bone marrow and liver.
• In postnatal life:
I. Upto 5-6 years: red bone marrow of all bones.
II. 6th to 20th : membranous bones, long bones.
• Red marrow is replaced.
• During disorders of bone, red cells produced in spleen.

15. • In skeleton:
1. Skull
2. Sternum
3. Ribs
4. Humerus
5. Vertebrae.
• in adult jaw:
1. tuberosity
2. Symphysis
3. Angle.

16. Red blood cell
• Non nucleated formed elements
• Count – males
- females
• Normal size: diameter – 7.2 microns
thickness
surface area and volume
• Advantages of biconcave shape:
– Rapid diffusion
– Large surface area
– Squeeze through capillaries.

17. ERYTHROPOIESIS
• 4 important changes occur:
1. Reduction in size – 25 to 7.2 microns
2. Disappearence of nucleus
3. Appearance of haemoglobin
4. Change in staining properties of cytoplasm.

18. Factors necessary for Erythropoiesis
1. GENERAL FACTORS:
 Erythropoietin :
• Source: juxta glomerular cells
• Stimulant: hypoxia
• Actions : proerthroblast production, maturation and release rbc
• Some other hormones: in hyperthyroidism , polycythemia.
• Other factors:
– Growth inducers like interlukin 3
– Vitamin B,C,D.

19.  MATURATION FACTORS:
1. Cynacobalamine : antipernicious factor.
• Source : mostly diet, liver.
transported to BM to promote maturation
intestinal flora – extrinsic factor.
• Action : DNA synthesis.
deficiency leads to – maturation of nucleus, reduce cell division.
2. intrinsic factor of castle – hematinic principle.
3. Folic acid – cells larger , megaloblasts

20. HEMOGLOBIN
• Molecular weight : 68,000.
• Normal values:
• Average hemoglobin (Hb) -- 14 to 16 gm%.
• At different ages:
– At birth : 22 – 25 gm%
– After 3rd month : 18 – 20 gm%
– After1 year : 17 gm%
– In adult males : 14 – 17 gm%
– In adult females : 12 – 16 gm%

21. Structure of hemoglobin
• Conjugated protein
• Protein part is globin and iron containing pigment is heme.
 Iron : ferruos form Fe++ , unstable form
 Porphyrin : tetrapyrole.
attached by CH4 bridges
iron attached to N- of each pyrole ring and N- of
globin molecule
 Globin : molecular weight : ALPHA – 15126, BETA - 15886
AA : 141 146

23. TYPES OF Hemoglobins .
• HbA – 95 to 98%
• HbA2 – 2 to 3 %
• HbF – upto 2%
• ABNORMAL Hb.
1. Sickle cell anemia – HbS
2. Thalessemia

24. Glycated hemoglobin
• HbA1C levels.
• Normal - 4-6 %
• Good diabetic control - < 7.0%
• Moderate diabetic control - 7.0-8.0%
• Poor diabetic control - > 8 %

25. Erythrocyte Sedimentation Rate(ESR)
• The rate at which the cells settle down is called ESR.
• It’s the length of clear supernatant plasma measured in mm after
the end of 1 hr.
• TYPES :
– Westergens method – 3.8% Na citrate.
– Wintrobes method – EDTA
• Values : males – 3 to 7 mm in one hr.
• females – 5 to 9 mm in one hr.
• Significance : prognostic value rather than diagnostic importance.

26. • Variations in ESR :
• Physiological : age, sex, menstruation, pregnancy( 3rd month to
9th – 35mm in one hour)
• Pathological :
• Increases : all anemias except sickle cell anemias, T.B, rheumatic
fever.
• Decreases : allergies, polycythemia.

27. Packed Cell Volume (PCV)
• PCV is the hematocrit value expressed as the percentage of
cellular elements with that of whole blood.
• Normal values
• In males: 40 – 45 %
• In females: 38 – 42 %
• Increased in
Polycythemia and
Decreased in
Anemia

28. Blood indices
• Following are the various blood indices:
1. Mean corpuscular volume(MCV)
2. Mean corpuscular hemoglobin(MCH)
3. Mean corpuscular hemoglobin concentration(MCHC)

29. Mean Corpuscular Volume(MCV)
• It is the average volume of a single red blood cell.
• Normal – 78 to 90 cu.microns
– Increased-
• Pernicious anemia
• Megaloblastic anemia
– Decreased-
• Microcytic anemia

30. Mean Corpuscular Hemoglobin(MCH)
• Quantity or amount of Hb present in one red blood cell
• Normal value of MCH is 30 pg (27 to32pg)
• Increases or remains normal
• Pernicious anemia
• Megaloblastic anemia
• Decreases in hypochromic anemia

31. Mean Corpuscular Hemoglobin
Concentration(MCHC)
• Quatity of Hb present in 100 ml of RBC.
• Amount of Hb present in relation to volume , so expressed in
percentage.
• Most important absolute value in diagnosis of anemia.
• Normal – 30 to 38 %.
• Decreased particularly in microcytic hypochromic ( iron
deficiency) anemia.

32. Anemia
Morphological :
• Normocytic normochromic
• Macrocytic normochromic
• Macrocytic hypochromic
• Microcytic hypochromic
Etilogical :
• Iron deficiency anemia
• Megaloblastic anemia
• Hemolytic anemia
• Aplastic anemia

33. Polycythemia:
• Polycythemia vera
• Secondary polycythemia
Hemoglobinipathies:
• Sickle cell anemia
• Thalassemias

34. Iron Deficiency Anemia
• Causes :
• Physiologic : most common and relates to nutrional deficiency
– Teenage years : menstrual loss superimposed on growth requirements.
– Pregnancy : added demand to the fetus
• Pathologic : invariably due to excessive blood loss.
– G.I tract
– Hemorrhoids
– Peptic ulcers
– Esophagial varices.
– Excess uterine bleeding

35. • Clinical manifestations :
• Most imp sym is chronic fatigue
• Pallor of conj, lips , mucosa
• Brittle nails spooning
• Palmar creases
• Palpitations , shortness of breath, numb and tingle of fingers,
bone pain.

36. • Oral manifestations
• Ang che – 58%
• Glosittis – 42 %
• Pale mucosa – 33%
• Oral candida – 25%
• Recurrent apthous – 8%
• Burning mouth – 8%
• High prevalnce due to:
• Impaired cell immunity
• Deficient bactericidal activity of pmn
• Decrease in mean epithelial thickness

37. • Oral health considerations:
• Hb levels < 8gm% , physician consultation before surgery.
• General anesthesia avoided.
• Potential for clinical bleeding and delayed healing should be
recognised.
• Dentists should be aware, patient at risk of IHD.

38. • Plummer – Vinson syndrome:
• Triad :
• Dysphagia – painless and limited to solids.
• Symptoms of anemia
• Splenomegaly, enlarged thyroid and alimentary tract cancers.
• Treated effectively with iron supplementation.

39. Megaloblastic (Pernicious) anemia
• Causes :
• Food – cobalamine malabsorption syndrome( >60% cases)
• Pernicious anemia ( 15-20%)
• Insufficient dietary intake.
• Autoimmune disease – Ab against IF and gastric parietal cells
• HLA types – A2, A3, and B7 and A blood group.
• Assosciation with thyroid disorders, type 1 DM.

40. CLINICAL MANIFESTATIONS
• HEMATOLOGIC:
• MEGALOBLASTIC ( macrocytic) anemia.
• Pancytopenia.
• Neurologic :
• Paresthesias, tingling and numbness of hands and feet.
• unco-ordination and muscle weakness.
• Impaired sense of smell.
• Psychiatric :
• Fatigue, irritability, mild dementia.
• Cardiovascular : risk of MI and Stroke.

41. • Oral manifestations :
• Glossitis, glossodynia , glossopyrosis
• Smooth and bald tongue – hunters/moeller’s
glossitis.
• Dysphagia and taste alterations seen.
• Nonspecific , persistent or recurrent stomatitis of unexplained
local origin may be an early clinical manifestation.

42. Hemolytic anemia
• Accelerated destruction of RBC’s can be caused by one of three
basic mechanisms:
1. A molecular defect : hemoglobinopathy
2. Abnormality in membrane structure and function
3. Enviornmental factor – mechanical trauma.

43. Sickle cell anemia
• Most common prevalent genetic hematologic disorder.
• Hemoglobin gene mutation :
• Replacement of glutamic acid by valine in 6th position of β-globin
chain
• Sickle shape – reduced plasticity , 14 days
• Transmitted as mendelian dominant
Disorder.
• Hetrozygous – sickle cell trait (AS)
• Homozygous – sickle cell disease (AA)

44. CLINICAL MANIFESTATIONS
• More common in females
• Invasive infections, acute chest syndrome(morbidity).
• Proinflammatory – sickle erythrocytes – trigger vaso-occlusive
crisis.
• Precipitating for sickle cell crisis is infection, and cases of
periodontal infection and mandibular osteomyelitis are
reported.

45. Oral manifestations
• Radiographic :
• “Stepladder” trabecular pattern(70%), enamel hypoplasia(24%),
calcified canals(5%).
• Pallor and delayed eruption of teeth
• Interruption of blood supply can result in anesthesis of IAN and
pulpal necrosis.

46. Oral health considerations
• Perceived risk of infectious complications is highest for,
extractions, restorative treatment and tooth polishing.
• Antibiotic prophylaxis .
• Aggressive treatment of oral infection
• Maintain good oral hygiene.
• Nitrous oxide can be used with adequate flow rates.

47. Thalassemias
• Disturbance of either alpha or beta Hb chain
production.
• β-thalassemia ( cooleys anemia) –
homozygous form.

48. • Clinical manifestations:
• Fatigue, weakness, pale skin.
• Osteporosis and growth retardation.
• Hair – on end effect on radiographs
• Oral manifestations:
• Taurodontism, attenuated lamina dura,
• Enlarged marrow spaces,
• Absence of alveolar canal,
• Class 2 – chipmunk facies.

49. Polycythemia
• Abnormal increase in the number of red blood cells , usually
with an increased hemoglobin level.
• Primary – true idiopathic increase
• Secondary – bone marrow anoxia or production ESF.

50. Clinical MANIFESTATIONS
• Vertigo, visual disturbance , tinnitus.
• G.I pain
• Paresthesis.
• Patients are prone to the development of blood clots.
• A major thrombotic complication (e.g.heart attack,stroke,DVT.)
may sometimes be the first symptom or indication that a person
has polycythemia vera.
• Erythromegaly

51. Oral manifestations
• Deep purplish red,
• Gingiva often engorged and swollen, bleed on slightest
provocation.
• submuosal petechiae are also common, ecchymoses and
hematomas.
• Control hemorrhage primary goal in treatment.

52. Blood groups
• ABO Blood group system.
• Karl Landsteiner – 1901
• Rh- system – Landsteiner and Weiner – 1940
•

53. 1. If a particular antigen is present in the red blood cells,
corresponding antibody must be absent in the serum
2. If the particular antigen is absent in the red blood cells, the
corresponding antibody must be present in the plasma

54. Inheritance
• The A and B agglutinogens – 6th month
• Conc. At birth – 1/5th of adult conc.
• Also in salivary glands, pancreas , kidney , liver , lungs –lewis
blood group.
• Agglutinins only after birth- gamma globolins- IgM and IgG.
• Gene A and B – DOMINANT
• Gene 0 – recesssive.

55. Erythroblastosis fetalis
1. 28-34 weeks
2. 48 hours
3.Transfusion

56. Transfusion reactions
• Hemolysis – bilurubin released – hemolytic jaundice.
• Increased viscosity – cardiac shock
• Renal shut down
• Transfusion transmitted infections seen.
• Transfusion assosciated lung injury. acute respiratory distress,
often associated with fever, non-cardiogenic pulmonary edema,
and hypotension.

57. Blood groups and periodontal disease
• A- Gingivitis
• O- Periodontitis
• AB- least prevalence in periodontitis
• B – MORE SEVERE PERIODONTITIS.

59. BLOOD

60. Contents
• Introduction
• Morphology of WBC
• Normal counts
• Variations in cell count
• Properties and functions
• White blood cell disorders

61. • Quantitative disorders
• Qualitative disorders
• Leukemia and periodontium
• Platelets
• Variations in counts.
• Conclusion
• References

62. Introduction
• Term derived from ‘leukos’
• Colourless and nucleated
• Role in defence mechanism
• They differ from rbc in :
– Larger
– Irregular
– Nucleated
– Life span

63. • Total WBC count
• Differential WBC count
3000-6000
0-100
150-450
200-600
1500-2700

64. Physiological variations
1. Age : In infants -- 20,000 per mm3 In children-- 10,000 to
15,000 per mm3 of blood.
2. Sex: Slightly, M > F. In females, increases during menstruation,
pregnancy and parturition.
3. Diurnal variation: Min. in early morning & max. in afternoon.
4. Exercise: Increased
5. Emotional conditions: like anxiety - Increased.
6. Sleep: Minimum.

65. Properties
• Diapedesis – squeeze through
• Ameboid movement – protrusion of cytoplasm and change in
shape
• Chemotaxis -
• Phagocytosis

66. Neutrophils
• Small granules in cytoplasm.
• Nucleus – bilobed ( no. depends on age of cell)
• 2-5 lobes
• Diameter – 10-12 microns
• Granules :
1. Primary / azurophilic –hydrolase,mpo,mmp
2. Secondary
• Life span – 2-5 days.
• Functions :
1. First line of defence
2. Phagocytosis.
3. PAF – blood loss

67. Eosinophils
• Coarse granules
• Spectacle shaped nucleus
• Diameter – 10-14 microns
• Eosinophilic granules
1. Eosinophil peroxidase- worms, tumor cells
2. ECP
3. MBP
4. CYTOKINES – interleukin 4,5
• Life span – 7 – 12 days
• Functions : defence against parasites,
• detoxification, disintegration
and removal of foreign proteins.

68. Basophils
• Bilobed nucleus
• Diameter – 8 – 10 microns
• Basophilic granules:
1. Heparin – i.v clot
2. Histamine
3. Proteases and MPO
• FUNCTIONS :
• Allergy or acute hypersensitivity reactions.

69. Monocytes
• Largest – 14-18 microns
• Cytoplasm – clear
• Nucleus – oval,bean,kidney.
• Life span – 48-72 hrs in blood,
3 months in tissues.
• Functions:
1. Motile and phagocytic
2. Precursors of tissue macrophages: kupffer cells, alveolar
macrophages, spleen.

70. Lymphocyte
• Nucleus – occupies whole of cytoplasm
• Size : large – 10-12, small – 7-10
• Function : T cells – cellular, B cells – humoral .
• Life span – ½ to 1 day.

71. Neutropenia
• Low absolute count for greater than 6 months
• Normal absolute number of neutrophils in the peripheral blood
: 3000 - 6000/mm3
• The risk for stomatitis, gingivitis, cellulitis increases < 1000cell/μl
• Mild – 1000-2000/mm
• Moderate – 500-1000/mm
• Severe – less than 500/mm

72. • Idiopathic
• Familial
• Secondary to viral infections- monitoring until recovery
• Secondary to systemic diseases
• Drug induced – discontinuation , diagnosis and cure
• Acquired common than congenital
Neutropenia associated with periodontal problems
• Cyclic neutropenia
• Chronic benign neutropenia
• Chronic idiopathic neutropenia

73. Cyclic neutropenia
• Repetative episodes of fever, ulcers, and infections.
• Periodicity of 21 days
• Autosomal dominant – mutation of neutrophil elastase(pri
granule)

74. Oral manifestations
• Periodic ossilations assos. With fever and mouth ulcers is hall
mark
• Inflamed gingiva, rapid periodontal breakdown, alveolar bone loss
(Gorlin & Chaudhry)

75. CHRONIC BENIGN NEUTROPENIA
• Glansslen 1941
• Infants and children
• ANC<500/μl, but normal WBC COUNT , lympho and mono.
• Cause : anti-neutrophil antibodies, IgG – 80 TO 100%

76. • Gingiva: hyperplastic, oedematous,fiery red,desquamation.
• Isolated areas of gingival recession,
• pocket formation and horizontal bone loss
• Extereme mobility of deciduous dentition

77. Management
• Plaque control
• Antiseptic mouthwash & antimicrobial therapy: Acute episode
• Periodontal surgery: WBC count is high
• Antibiotic coverage

78. Agranulocytosis
• Agranulocytosis is a serious condition characterized by an
extremely low leukocyte count and the absence of neutrophils
• Cause: drug idiosyncrasy
• Onset – fever, malaise, general weakness, sore throat
• Ulceration- oral cavity, oropharynx, throat , characteristic
• Isolated necrotic patches
• Absence of inflammatory reaction
• Gingival margin
• Increased salivation and fetid odor.

79. CHEDIAK-HIGASHI SYNDROME
• Chediak (1952), Higashi (1954)
• Rare autosomal recessive defect
• Oculo-cutaneous albinism,easy bruisability, and bleeding
• Presence of abnormal lysosomal inclusions
• Impair neutrophil migration, defective granulation,
• Abnormal granules not discharging their lysosomal content against the
engulfed bacteria.
• Unable to metabolize and digest microbes.
• Viable bacteria found in the cytoplasm.

80. Oral manifestation
• Severe gingival inflammation
• Excessive and early periodontal destruction resulting in
premature loss of permanent dentition.

81. ORAL HEALTH CONSIDERATIONS
• Excessive operative blood loss anticipated secondary to
qualitaive defects in platelet function.
• I.m injections are avoided
• Photophobia- sensitive to bright operatory light, sunglasses.

82. LEUKOCYTE ADHESION DEFICIENCY
• Anderson and springer 1986
• Inability to produce or failure to express cell surface integrin (CD
11 & 18)
• Inspite of leucocytosis , fail to migrate
• 2 types:
• LAD I: deficiency in integrins- adhesion defect
• LAD II: Selectin-ligand deficiency- rolling defect

83. • Oral manifestation:
• Extremely acute gingival inflammation and proliferation of gingival
tissues with rapid destruction of bone.
• Primary & permanent dentition, result in early tooth loss.

84. PAPILLON LEFEVRE SYNDROME
• Autosomal recessive disorder
• Palmo-plantar keratosis,aggressive periodontitis,calcification of
dura.
• Edentulous

85. • Preus has hypothetised, defect is in the epithelial barrier, leads
to reduced host defence against periodontopathic bacteria
• Microscopy – marked inflammation of lateral pocket wall,
osteoclastic activity, exteremely thin cementum.

86. Downs syndrome
• Trisomy 21, mental deficiency & growth retardation
• Poor chemotaxis and phagocytosis of neutrophils
• Moderate gingivitis
• High prevalence of periodontal disease
• P . Intermedia – high prevalance

87. Leukemia
• Malignant neoplasia of WBC precursors :
• Diffuse replacement of the bone marrow with proliferating
leukemic cells
• Abnormal number and forms of immature WBCs in the
circulating blood
• Widespread infiltrates in the liver, spleen, lymph nodes and
other body sites

88. Leukemia and periodontium
• LEUKEMIC INFILTRATION
• Gingiva, less frequently in alv. bone
• Highest incidence :
• Acute monocytic leukemia (Dreizen et al )
• Gingiva: Bluish red & cyanotic,
enlarged
• Infiltration of gingival corium.

89. • BLEEDING:
• gingival hemorrhage
• Early sign
• Thrombocytopenia and anemia
• petechiae and ecchymoses
• Side effect of drugs
• ORAL ULCERATION AND INFECTION:
• Discrete punched out ulcers penetrating deeply into the submucosa
and covered by a firmly attached white slough
• Acute gingivitis and lesions resembling necrotizing ulcerative gingivitis
are more frequent in terminal case of acute leukemia

90. Management
1.Physician’s consent
2.Before chemotherapy: complete periodontal treatment plan
• BT, CT, PT, platelet count
• Antibiotic coverage
• Extraction atleast 10 days before chemotherapy
• Oral prophylaxis, chlorhexidine mouthwash
3. Acute leukemic conditions: emergency periodontal care
4. Oral ulceration & mucositis: palliative treatment
5. Chronic conditions

91. PLATELETS
• Small, colourless, non-nucleated, moderately refractive bodies
• Fragments of cytoplasm
• Diameter – 2-4 microns.
• Structure
1. Cell membrane:
1. Glycoproteins – adherence
2. Phospholipids – clotting, thromboxane A2
2. Microtubules: structural support to maintain shape
3. Cytoplasm: cell organneles, thrombosthenin- clot retraction.
• Life span – 8-12 days.

92. • Properties :
1. Adhesiveness – collagen, thrombin, Ca, ADP,
2. Aggregation – ADP and THX A 2, PAF
• Functions :
1. Blood clotting – intrinsic prothrombin activator.
2. Role in clot retraction

93. Physiologic variations
• Age – less in infants, 3rd month.
• Sex – same, reduced in menstruation
• High altitude – increases

94. • Thrombocytopenia :
– Acute infections, aplastic or pernicious anemia,typhoid, T.B
• Thrombocytosis : hemorrhage,splenectomy.
• Thrombocythemia : chronic leukemia, hodgkins disease
• Glanzmann thrombasthenia: defective clot retraction

95. Conclusion

96. References
• Essentials of medical physiology - K Sembulingam, 5th edition
• Medical physiology – Ganong , 3rd edition
• Carranza’s Clinical Periodontology - 10th Edition
• Burkets Oral medicine-10th edition
• Pathologic basis of disease – Robbins and Cotran, 8th edition.
• Shafer’s textbook of Oral Pathology- 6th edition
• David E Dias, Scott Mackey - Systemic disease and
periodontitis:periodontology 2000, vol. 32, 2003.