Basic concepts of endocrine system explained

Basic concepts of endocrinology

1. Endocrinology

2. Contents Introduction General principles of endocrinology Pituitary gland Anterior pituitary Posterior pituitary Growth hormone Hormonal excess Growth Hormone excess Acromegaly Gigantism

3. Dwarfism Thyroid Stimulating Hormone Thyroid hormones Adrenocorticotropic hormone Prolactin Hyperprolactinemia Luteinizing Hormone and Follicle Stimulating Hormone Anti-diuretic hormone Diabetes insipidus Oxytocin Hypopituitarism and periodontium Hyperpituitarism and periodontium Conclusion references

4. Introduction The multiple activities of the cells, tissues and organs of the body are coordinated by the interplay of several types of chemical messenger systems. Neurotransmitters Endocrine hormones Neuroendocrine hormones Paracrines Autocrines Cytokines

5. General principles of endocrinology Cell function is broadly controlled by: Neural control Endocrinal control Neural control Endocrinal control Due to depolarisation through the nerve Hormone directly into the blood stream Rapid action due to shorter latent period Much longer latent period Affects certain group of cells for a shorter period

6. Endocrine glands Also known as ductless glands Secrete hormones directly into the blood stream Hypothalamus Anterior pituitary Posterior pituitary Pancreas Adrenal cortex Adrenal medulla 7. Thyroid 8. Parathyroid 9. Kidney 10. Ovary and testes

7. Other organs with endocrine function and hormones Organ Hormone Heart Anti-Natriuretic Peptide( ANP) GIT Cholecystokinin-pancreozymin Secretin and vasointestinal peptide(VIP) Kidney 1,25-Dihydroxycholecalciferol Pineal gland Melatonin Skin Calciferol Liver Insulin Like Growth Factor( IGF) Platelets Platelet Derived Growth Factor Lymphocytes Interleukins

8. Hormone Greek- Hormacin “ I excite or arouse” Introduced by Starling in 1905 Def: secretory products of ductless glands released directly into the circulation in small amounts to a specific stimulus and on delivery in circulation produces a response on the target cells Interact with target cells via receptors- specific binding sites Most hormones are metabolised rapidly after secretion and gets inactivated mainly in liver and kidney

9. Classes of Hormones I)Based on mechanism of action: Group 1- Bind to intracellular receptors eg : androgens, calcitriol, estrogens, glucocorticoids, thyroid hormone Group 2- Bind to cell surface receptors A)Second messenger cAMP ACTH, ADH, CRH, FSH, LH B)cGMP as second messenger Atrial natriuretic factor Nitric oxide

10. C)Calcium/phosphatidyl inositols as second messenger GnRH, TRH, PDGF, Substance P D)Second messenger is a kinase/phosphate cascade Insulin, GH, Prolactin, Insulin like growth factors (IGF-1, IGF-2) II)Based on nature: -Steroid hormones -amine hormones -peptide hormones -protein hormones -glycoprotein hormones

11. III)Based on nature of action: -Local hormones eg : Testosterone -General hormones eg : Insulin, Thyroid hormone IV)Based on effect: -Kinetic hormones -Metabolic hormones -Morphogenetic hormones V)Based on stimulation of endocrine glands: -Tropic hormones -Non-tropic hormones

12. PITUITARY GLAND Hypophysis Connected to hypothalamus – pituitary stalk Parts Anterior pituitary-adenohypophysis Posterior pituitary- neurohypophysis

13. Embryology Anterior pituitary- Rathke’s pouch Posterior pituitary from neural tissue outgrowth from hypothalamus

14. Anterior pituitary hormones 6 important hormones and other lesser important ones Plays a major role in control of metabolic functions throughout the body

15. Cells of anterior pituitary gland

16. Posterior pituitary gland Neurohypophysis

17. Nerve endings are bulbous and contain secretory granules 2 hormones: Anti diuretic hormone (ADH) or vasopressin Oxytocin ADH -primarily formed in the supraoptic nuclei ( neurophysin II) Oxytocin- paraventricular nuclei ( nerophysin I) These hormones are released from the endings by exocytosis.

18. Hypothalamus controls pituitary secretion Secretion from the posterior pituitary is controlled by humoral or nerve signals that originate in the hypothalamus and terminate in the posterior pituitary Secretion from the anterior pituitary is controlled by hormones- hypothalamic releasing and hypothalamic inhibitory hormones

19. Hypothalamic releasing and inhibitory hormones are secreted into the median eminence. Special neurons that originate in the hypothalamus, send nerve fibres to the median eminence and tuber cinereum, an extension of hypothalamic tissue into the pituitary stalk. Secrete releasing and inhibitory hormones into tissue fluids Hormones immediately absorbed into hypothalamo -hypophyseal portal system Sinuses in anterior pituitary gland

20. Hypopituitarism And Periodontium Increased gingival inflammation Resorption of cementum in molar furcation area Reduced apposition of cementum Decreased osteogenesis in interdental area Reduced vascularity in pdl Degeneration of the ligament with cystic degeneration and calcification of many epithelial rests Osteoporosis

21. Hyperpituitarism and periodontium Marked overgrowth of alveolar process Increase in size of dental arch Spacing of the teeth Food impaction Hypercementosis

22. GROWTH HORMONE Exerts its effects directly on all or almost all tissues of the body. Also called somatotropic hormone or somatotropin Promotes cell differentiation of specific cells such as bone growth cells, cell mitosis, early muscle cells.

23. GH promotes protein deposition in tissues Enhancement of Amino Acid transport through the cell membrane Enhancement of RNA translation to cause protein synthesis by ribosomes Decreased catabolism of protein and aminoacids

24. GH decreases carbohydrate utilisation Decreased glucose uptake in tissues such as skeletal muscle

25. GH stimulates cartilage and bone growth Increased deposition of protein by chondrocytic and osteogenic cells that cause bone growth Increased rate of reproduction of these cells Specific effect of converting chondrocytes to osteogenic cells , thus causing deposition of new bone 2 principal mechanisms of bone growth: GH long bones grow at the epiphyseal cartilages Osteoblasts in the bone periosteum and in some bone cavities deposit new bone on the surface of older bone. Osteoclasts remove old bone. When the rate of deposition is higher thickening of bone GH strongly stimulates osteoblasts

26. Effect skeletal muscle Increases the growth of skeletal muscle by increasing protein synthesis Causes hypertrophy of skeletal muscle cell Promotes activity of satellite cells of skeletal muscle Effect on visceral organs Growth of liver, kidney, heart pancreas and intestine Due to hypertrophy and hyperplasia Effect on fat metabolism Lipolysis and increased plasma FFA Promotes ketogenesis

27. Effect on electrolyte and water metabolism Increases plasma Ca 2 + Causes Na + retention Maintains ECF volume Increases plasma phosphate level

28. Somatomedins GH hormone acts on liver and causes the production of somatomedins Small protein molecules Potent effect on bone growth Almost 4 types have been identified, somatomedin C is important IGF-1 Conc. in plasma closely follows the rate of GH secretion GH cause the formation of enough somatomedin C in the local tissue to cause local growth.

29. GH regulation After adolescence secretion decreases slowly with aging, finally falling to about 25% of adolescent level in old age. GH secreted in a pulsatile pattern, increasing and decreasing Normal conc-1.6-3ng/ml adults Child or adolescent-6ng/ml

30. GH secretion and aging Aged appearance due to the decreased protein deposition Increased fat deposition Increased wrinkling of the skin Diminished rates of function of some organs Diminished muscle mass Maximal release during the intense growth periods of late childhood and adolescence Age Concn (ng/ml) 5-20 yrs 6 20-40yrs 3 40-70yrs 1.6

31. Classification of diseases of the pituitary and hypothalamus primary secondary Hormone excess 1. Anterior pituitary Prolactinoma Acromegaly Cushing’s syndrome Disconnection hyperprolactinemia 2 hypothalamus and posterior pituitary Syndrome of inappropriate ADH (SIADH) Hormone deficiency 1. Anterior pituitary Hypopituitarism Eg: GnRH deficiency ( Kallman’s syndrome) 2. Hypothalamus and posterior pituitary Cranial diabetes insipidus Hormone resistance GH resistance ( Laron dwarfism) Non- functioning tumors Pituitary adenoma Craniopharyngioma Metastatic tumors

32. Hormonal excess Overgrowth –Adenomas Pituitary adenomas are classified as Microadenomas (<1cm) Macroadenomas (>1cm)

33. Pituitary apoplexy Infarction of the pituitary Due to sudden haemorrhage within the tumour Symptoms Sudden and severe headache Diplopia Extension of the tumour inferiorly- rare

34. Abnormalities of GH secretion Panhypopituitarism Dwarfism Gigantism Acromegaly

35. Panhypopituitarism Decreased secretion of all anterior pituitary hormones. Congenital or sudden or slowly after birth due to adenomas

36. Gigantism GH excess occurs before the completion of linear growth (before closure of epiphyseal plates) Mild to moderate obesity Tall stature Progressive macrocephaly Could be related to pituitary adenoma Accelerated growth

37. Radiographically: enlarged sella Other features: Enlargement of soft tissues Enlarged mandible Increased size of hand and feet Generalised macrodontia Treatment: Surgical removal of adenoma Radiation therapy Oral manifestations: Prognathic mandible, frontal bossing, dental malocclusion, and interdental spacing are the other features which may be seen in such individuals. Intraoral radiograph -hypercementosis of the roots.

38. Acromegaly GH excess occurs after the growth plates have fused Usually with pituitary adenoma Average age of diagnosis -42 years

39. Features Macrognathia, macroglossia, large diastemas Mandibular prognathism Apertognathia The lips become thick and negroid . Intraoral spacing buccal tipping of the teeth due to enlarged tongue Hypertrophy of soft palatal tissues

40. Radiograph -large pulp chambers ( taurodontism ) and excessive deposition of cementum on the roots.

41. Diagnosis : serum IGF-1 levels along with oral Glucose Tolerance Test

42. Treatment Surgical removal of the mass Radiation therapy Pharmacotherapy  somatostatin analogues (octreotide, lanreotide,vapreotide )

43. PITUITARY DWARFISM Caused by Diminished production of GH by anterior pituitary Reduced capacity of the tissues to respond to GH Clinical features: Short stature Small face Smaller maxilla and mandible Delayed eruption Delayed shedding Reduced size of the teeth

44. Lab diagnosis: Radioimmunoassay for GH Treatment : Replacement therapy with human GH ( if detected before closure of epiphyseal growth plates) If GH deficiency is caused by hypothalamic defect- GHRH is appropriate No treatment for GH receptor lacking patients Prognosis: Identified and treated at early age  normal height

45. Thyroid hormones The principal hormones synthesized and secreted by thyroid gland are: T4 (thyroxine) T3 (triiodothyronine). RT3 (reverse­-triiodothyronine), secreted in small quantity. Calcitonin T4, T3, and RT3 -thyroid follicles Calcitonin -parafollicular cells (C cells).

46. Thyroid Hormone Synthesis The thyroid hormone synthesis involves following steps: Iodide trapping Conversion of iodide into iodine Thyroglobulin synthesis Proteolysis of thyroglobulin Secretion of thyroid hormones

47. In a normal individual, total plasma T4 concentration is about 8 µg/dL, and plasma T3 is about 0.15 µg/dL. Free T4 level in plasma is about 2 ng/dL, and free T3 is about 0.3 ng/dL Thyroid hormones bind with three types of plasma proteins: Thyroxine binding globulin (TBG) Thyroxine binding prealbumin (TBPA) Albumin. Normally, T4 binds mainly with TBG and TBPA, and T3 binds with albumin and TBG.

48. Fasting decreases conversion of T4 to T3. RT3 is increased and T4 remains normal in fasting. In starvation (chronic and severe fasting), RT3 returns to normal, but T3 continues to remain low. In overfeeding , opposite happens; T3 is increased and RT3 is decreased.

49. Clinical correlation Hyperthyroidism Thyrotoxicosis Grave’s disease Thyroid storm Hypothyroidism

50. Thyroid Stimulating Hormone Glycoprotein Controls the secretion of T3 and T4 2 subunits α and β Secreted by thyrotrophs of anterior pituitary Mechanism of Action : TSH exerts its effects on thyroid cells by increasing concentration of intracellular cyclic AMP.

51. Functions : Facilitates iodide uptake Enhances intermolecular coupling and thyroglobin synthesis and secretion into colloid Stimulates release of thyroid hormones and iodotyrosines from the gland Promotes endocytosis of colloid Increases blood flow to the thyroid gland Causes hypertrophy and growth of the thyroid gland

52. Clinical correlation: Decreased secretion of TSH due to pituitary diseases results in thyroid atrophy and decreased secretion of thyroid hormones (secondary hypothyroidism or hypopituitary hypothyroidism). Chronic increase in TSH secretion results in hypertrophy of thyroid gland, called Goitre.

53. Hyperthyroidism Hypersecretion of thyroid hormones from thyroid gland or from extrathyroidal tissues, Two types primary secondary Hyperthyroidism occurs due to pathology of the thyroid gland- primary hyperthyroidism.

54. The common causes are: Adenoma of thyroid Multinodular Goiter Metastatic carcinoma of functioning thyroid gland Graves’ disease Activating mutation of TSH receptors Iodine excess ( Jod-Basedow phenomenon)

55. Secondary Hyperthyroidism When hyperthyroidism occurs due to the pathology outside thyroid gland Pituitary causes-Tumor of thyrotrophs of anterior pituitary (secretes excess of TSH). Extrathyroidal Causes- Chronic excess administration of thyroid hormones (iatrogenic), tumor of ectopic thyroid tissue (lingual thyroid), human chorionic gonadotropin secreting tumors such as choriocarcinoma.

56. Hypothyroidism Hypothyroidism in adult –Myxedema Children- Cretinism Primary Hypothyroidism- due to the diseases or causes that primarily affect thyroid gland Secondary Hypothyroidism- primarily due to a defect outside the thyroid gland ( pituitary or hypothalamus)

57. Symptoms Cold intolerance, weakness and easy tiredness dry­ thick skin, loss of hair poor memory and inability to concentrate, constipation (due to decreased GI motility), weight gain in spite of poor appetite thick and husky voice yellow skin, psychosis (myxedema madness) menorrhagia (in females), galactorrhea and infertility Signs Cool extremities with dry coarse skin, dry hair puffy face, with edematous hands and feet ( myxedema ) diffuse alopecia goiter , bradycardia, hyper tension (diastolic), anemia , decreased reaction time of tendon reflexes (especially, delayed Achilles tendon reflex relaxation), carpal tunnel syndrome and periorbital edema .

58. Treatment of Hypothyroidism : Thyroid hormone replacement T4 is instituted at a dose (usually 10 to 15 µg/kg/ day) Hashimoto’s Thyroiditis - chronic form of autoimmune thyroiditis antibodies are formed against the thyroglobulin and thyroid peroxidase. thyroid cells are damaged -  hypothyroidism develops.

59. Oral manifestations of thyroid disorders and its management: Dental management of hypothyroidism: Patients who have hypothyroidism are susceptible to cardiovascular disease from arteriosclerosis and elevated LDL. -anti coagulant therapy Antibiotic prophylaxis Drug actions and interactions - sensitive to central nervous system depressants and barbiturates Dental management of hyperthyroidism: -Susceptibility to infection -Drug actions and interactions : acetylsalicylic acid is contraindicated in patient with hyperthyroidism -Epinephrine- contraindicated

60. Cretinism When hypothyroidism develops from or before birth, the patients are called cretins. Causes: Maternal iodine deficiency during pregnancy, maldevelopment of thyroid gland during fetal life, inborn errors of thyroid hormone synthesis antithyroid antibodies in mother that crosses placenta and enters fetal circulation hypopituitarism in fetal life Patients are dwarf and mentally retarded. Typically, they have potbelly and protrusion of tongue

61. Adrenocortiocotropic hormone (ACTH) Controls growth and secretion of adrenal cortex. Influences the secretion of cortisol. ACTH plays vital role in physiology of stress and pathophysiology of stress disorders. secreted from corticotrophs of anterior pituitary synthesized as part of a larger molecule called pro-opiomelanocortin (POMC), which cleaves to form β-lipotropin, and ACTH in human beings Mechanism of Action :ACTH acts primarily by increasing cAMP in the target cells.

62. Circadian Rhythm of ACTH Secretion Normally, ACTH secretion occurs in irregular bursts. The pulsatile secretion of ACTH is due to several bursts of CRH (corticotropin releasing hormone) secretion in 24 hours. However, there is a prominent diurnal rhythm for ACTH secretion, in which secretion is more in the early morning, which constitutes about 75% of the total 24 hours secretion

63. - This diurnal variation in ACTH secretion is due to the natural sleep-­wake cycle, controlled by inherent biological rhythm of suprachiasmatic nucleus of hypothalamus. - The pattern of secretion is reversed in individuals who sleep in the day and remain awake during night. The pattern of glucocorticoid secretion closely follows the ACTH secretion

64. Regulation of ACTH Primary factor controlling the ACTH secretion is CRH secreted from hypothalamus Factors that Increase ACTH Secretion Corticotropin releasing hormone, ADH, sleep­wake transition, stress (hypoglycemia, surgery, anesthesia, injury, infection, fever, etc.), anxiety, depression, α receptor agonist, β receptor antagonist, serotonin, acetylcholine, interleukins, and GI hormones. Factors that Inhibit ACTH Secretion Cortisol, somatostatin, GABA, natriuretic peptide and opioids.

65. Functions ACTH stimulates synthesis and secretion of cortisol and other steroid hormones from adrenal cortex The impact of ACTH is more on glucocorticoid secretion than on other steroids. ACTH stimulates growth and activity of melanocytes. This results in hyperpigmentation of the skin due to increased synthesis of melanin. Acts as a local neurotransmitter. ACTH influences immunity by controlling secretion of cytokines from lymphocytes. Cytokines also stimulate ACTH secretion.

66. Prolactin Hormone for milk synthesis Also influences development of the mammary gland, reproductive functions and immune responses. prolactin is secreted from the lactotrophs Lactotroph population increases during pregnancy, lactation, and estrogen therapy. Prolactin is synthesized as preproprolactin that forms proprolactin , which finally forms prolactin. After synthesis, the hormone is stored in the granules of the lactotrophs and on appropriate stimulation, secreted into circulation.

67. Regulation of Secretion Prolactin secretion increases steadily during later part of pregnancy and attains peak at term. The increased prolactin secretion correlates with increase in plasma estrogen concentration during pregnancy: 1. Estrogen causes hyperplasia of lactotrophs though it does not stimulate prolactin synthesis. 2. Estrogen also increases responsiveness of lactotrophs to other stimuli that increase prolactin synthesis and secretion.

68. Factors that Decrease Prolactin Secretion Dopamine and its agonists and GABA. Somatostatin Prolactin stimulates secretion of dopamine and somatostatin, those in turn inhibit prolactin secretion. Factors that Increase Prolactin Secretion Prolactin releasing factor TRH pregnancy estrogen therapy nursing (breastfeeding), Sleep and stress angiotensin­ II, oxytocin dopamine antagonists, serotonin

69. Physiological Effects Effects on Milk Synthesis and Secretion stimulate milk synthesis and secretion Effects on Breast Development hyperplasia of breast tissue before and after puberty. It also causes hyperplasia of breast tissue during pregnancy and lactation.

70. Effects on Immunity Prolactin is synthesized by immunocytes. The immunocytes number increases during pregnancy. Prolactin brings the immunologic balance required for acceptance of fetal tissue by the mother. Effects on Liver Increases synthesis of synlactin , an intermediary growth factor secreted from the liver. Therefore, it is believed that prolactin indirectly stimulates growth.

71. HypeRprolactinemia Etiology - Hyperplasia of lactotroph cells Decreased tonic dopaminergic inhibition of prolactin secretion Commonly diagnosed in females 20-40years Serum prolactin levels- elevated to very high Causes hypogonadism

72. Treatment: Dopamine agonists: Cabergoline or Bromocriptine. If not responding- transsphenoidal surgery

73. Gonadotropins Regulate growth and development of gonads, pubertal maturation and secretion of sex steroids. The secretion of gonadotropins is pulsatile, periodic, diurnal, cyclic, and seasonal. Secretion of both the hormones is mainly controlled by gonadotropin releasing hormone (GnRH) secreted from hypothalamus. MOA: Luteinizing hormone and FSH exert their effects by increasing cyclic AMP concentration in the target cells. Luteinizing Hormone And Follicle Stimulating Hormone

74. ANTI DIURETIC HORMONE Synthesized in Hypothalamus Kidney predominant site of action Reduces diuresis Results in overall retention of water Vasoconstriction at higher concentration

75. Factors Affecting ADH Secretion Factors that Increase ADH Secretion: Increased plasma osmolality decreased ECF volume decreased blood pressure angiotensin II Stimuli that Inhibit ADH Secretion: Decreased plasma osmolality increased ECF volume decreased temperature ethanol Cortisol thyroxine α- adrenergic agonist

76. ADH Receptors Two types of ADH receptors: V1 V2. V2 receptors are located on the kidney tubules. ADH increases permeability of the tubular cells by acting on the V2 receptors.

77. Functions of ADH Increase water reabsorption. Acting on blood vessels- causes vasoconstriction. Thus, in higher concentration it increases blood pressure. It causes contraction of smooth muscles of spermatic cord.

78. 5. Increases CRH release and therefore increases ACTH secretion Decrease cardiac output. ADH acts as a neurotransmitter in some areas of brain and spinal cord

79. DIABETES INSIPIDUS Decreased ADH Inability to hold water by kidneys Inadequate pituitary production of ADH or resistance to the action of ADH on kidneys

80. Symptoms : Polyuria Polydypsia Hypernatremia Compensatory polydipsia Daily urine output- 10-15L- severe dehydration Diagnosis- water deprivation test

81. Nephrogenic DI Etiology : In nephrogenic DI, ADH secretion is normal, but kidney is unresponsive to it due to receptor deficiency or abnormality. It may be acquired or genetic: 1. Acquired causes are usually due to drugs such as demeclocycline, rifampicin, aminoglycoside, lithium, cisplantin and amphotericin ischemia resulting in acute tubular necrosis, metabolic disorders such as hypercalcemia and hypokalemia

82. 2. Genetic disorders : X-linked recessive defect in which V2 receptor gene is deficient and autosomal defect in which aquaporin gene is deficient. Treatment: Chlorpropamide is used for treatment of the disease as it increases the renal response to ADH.

83. Neurogenic DI Etiology : Diseases of CNS in which hypothalamus, hypothalamo -hypophyseal tract or posterior pituitary are affected. Central , neurohypophyseal , pituitary type It occurs in Head injury Tumors such as craniopharyngeoma and suprasellar pituitary tumors infections such as meningitis and encephalitis, vascular lesions such as Sheehan’s syndrome and aneurysm of internal carotid artery, and congenital or genetic defects. ADH secretion is deficient in these conditions.

84. Treatment Injection of vasopressin. Clofibrate therapy.

85. SIADH- Syndrome of Inappropriate ADH Secretion Excessive secretion of ADH ADH secretion is inappropriately high relative to serum osmolality. SIADH is seen in: 1. Head injury 2. Ectopic production of ADH by some malignant tumors such as carcinoma of lungs, pancreas, ovary and bladder. 3. Neurologic diseases like multiple sclerosis, Guillain- Barré syndrome, brain abscess, meningitis, encephalitis, etc. 4. Drugs such as desmopressin, chlorpropamide, high dose of oxytocin, vincrisitine , phenothiazine, carbamazepine, etc.

86. In SIADH, dilutional hyponatremia natriuresis If SIADH is due to brain diseases, the condition is called cerebral salt wasting, and if due to lung diseases the condition is called pulmonary salt wasting.

87. OXYTOCIN Oxytocin is mainly synthesized in the paraventricular cells of hypothalamus though synthesis also occurs in supraoptic nucleus After synthesis, oxytocin is secreted into the posterior pituitary where it is stored .

88. Regulation of Secretion Oxytocin secretion occurs in response to two important physiological stimuli: Suckling at the time of breastfeeding Cervical dilatation at the time of parturition. Stressful stimuli facilitate oxytocin release. Oxytocin secretion is inhibited by alcohol.

89. Functions Oxytocin mediates two physiological reflexes: 1. milk ejection reflex 2. parturition reflex.

90. Clinical correlation Oxytocics (preparations of oxytocin) are used routinely for: Induction of labor. Oxytocic infusion is given to facilitate the progress of labor. It is routinely injected immediately following delivery, to prevent excessive postpartum hemorrhage, in which uterus contracts severely in response to oxytocic and bleeding vessels are compressed in the contracted uterus that prevents bleeding.

91. Conclusion Hormonal disturbances may affect the periodontal tissues directly as periodontal manifestations of the endocrine diseases, and this may modify the tissue response in gingival and periodontal disease. So a thorough knowledge of different hormones and its effect on periodontal tissues is important in managing such conditions.

92. References: Comprehensive textbook of medical physiology- GK Pal Vol 1- 1 st edition Davidsons’s principles and practice of medicine- edited by Brian R Walker, Nicki R colledge , Stuart H, Ian D- 22 nd edition Oral and maxillofacial pathology- Brad W Neville, Douglas D Damm , Carl M Allen, Jerry E Bouquot - 2 nd edition Glickman's Clinical Periodontology - Irving Glickman, Fermin A. Carranza- 7 th edition Textbook of physiology- AK Jain Burket’s Textbook of oral medicine. Michael Glick: 12 th edition