Endocrine System

1. Endocrine System Lecture 2 Parathyroid hormone, calcium homeostasis and suprarenal hormones Asso. Professor Dr Than Kyaw 24 September 2012

2. PARATHYROID GLAND • How many parathyroid glands in animals? • Located within or near thyroid gland • 2 pairs in most domestic animals, 2 on each side • External or internal (burried inside) parathyroids • Commonly one pairs is visible outside the thyroid gland • Pigs and birds – lack of internal parathyroids • 2 cell types • - Chief cells • - produce parathyroid hormone (PTH)/parathormone • -Oxyphil cells • - larger, less numerous (found in horse, cattle and man) • - function unknown

3. Left thyroid and parathyroid glands 1. Normal Thyroid Gland2. Parathyroid Gland3. Parathyroid Gland4. Enlarged Thyroid Gland

5. PARATHYROID GLAND • Parathormone • Polypeptide hormone • Secreted in response to low serum Ca & phosphorus levels • Regulate calcium and phosphorus metabolism • Stored in • Secretory • vesicles • Formation of • active PTH • In Golgi • Precursor PTH • In RER • Secretion by • exocytosis

6. PARATHYROID GLAND • Parathormone Organs affected • primary effect of PTH is to increase Ca and decrease Phosphate concentrations in extracellular fluids • Bones – bone resorption • - osteocytes maintenance and turnover of the mineral content of the bone • - release of calcium and phosphate from bone • - bone formation by osteoblastsis inhibited • - Osteoclasts – bone resorption, removal of bone matrix

7. PARATHYROID GLAND • On kidney • Parathormone • Promote the formation of activeVitD by the kidney • Increase • Ca absorption • (Distal convoluted tubules of kidney) • Decrease phosphate reabsorption • (Proximal convoluted tubules of kidney • - Overall result of parathormone action on bone and kidney - increase in blood calcium and phosphorus

8. Parathormone and Vitamin D PTH Promotes production of enzyme α1-hydroxylase needed for • Vitamin D • Skin • (ultra violet light) • - diets • Further • metabolized in • kidneys Metabolized to 2nd precursors in the liver active form 1,25 dihydroxycholecalciferol (calcitriole) • 1st precursors • inactive form • 2nd precursors • inactive form • Vitamin D • Increases the rate of Ca and P absorption from GIT • Reduce loss of Ca in the urine

9. Parathormone is more important in the regulation of Calcium and Phosphorus than calcitonin.

10. Relationships of parathyroid hormones and other organs

11. HYPO-PARATHYROIDISM • Decreased PTH production • Rare both in animals and man • Hypocalcemia • Calcium is: • Deposited in the bones • Excreted in urine Cause: • Heredity • Idiopathic • Surgical removal of thyroid gland

12. Hypocalcemia in animals (Tetany/eclampsia) • Most common Ca metabolism disturbance occurs at the time of parturition. • Most frequent in dairy cows (milk fever) and dogs. • Affected animals - severe hypocalcemia - often severe neuromuscular dysfunction - recumbent (cow) and involuntary muscular spasm (dog) referred to tetany or eclampsia • The problem arises from sudden demand of Ca needed for milk production so that serum Ca concentration is no longer maintained within homeostatic limit.

13. Hypocalcemia in animals (Tetany/eclampsia) Cause • Cause of milk fever – complex one • It does not seem to involve a failure of PTH secretion - It may be due to impaired responsiveness of PTH target tissues (receptor expression) - impaired Vit D activation Treatment - infusion of glucose and calcium (calcium borogluconate) - the animal usually recover after the treatment

14. HYPOPARATHYROIDISM • Signs in man • Acute hypocalcemia • Tingling of the fingers • Chronic hypocalcemia • Fatigue, weakness • Personality changes • Loss of tooth enamel, dry scaly skin • Cardiac arrhythmia • Cataract

15. HYPOPARATHYROIDISM MANAGEMENT: • Ca supplement • VitD supplement – LIQ FORM: WITH WATER, JUICE OR MILK • Ca-gluconate

16. HYPERPARATHYROIDISM • Increased PTH production • HYPERCALCEMIA • HYPOPHOSPHATEMIA • Primary cause – Tumour orhyperplasia of the parathyroid gland • Secondary – Compensatory oversecretion of PTH in response to hypocalcemia from: • Chronic renal disease • Rickets • Malabsorption syndrome • Osteomalacia

17. Dietary Ca deficiency and hyperthyroidism • Insufficient Ca in diets - common in domestic animals • Especially diets formulated primarily on grain products • Chronically low intake of dietary Ca - stimulates increased secretion of PTH to keep blood Ca level for nerve and muscle function. • Ca is removed from bone matrix - bone decalcification - bone deformities - osteoporosis • k/s - Nutritional 2° hyperthyroidism • Ricketsin young • Bran disease or big-head disease in horse

18. PARATHYROID DIAGNOSTIC TESTS: • Hematological • Serum calcium • Serum phosphorus • Serum alkaline phosphatase • Urinary studies • Urinary calcium • Urinary phosphate – tubular reabsorption of phosphate

19. Adrenal Gland (Suprarenal gland)

20. Adrenal Gland (Suprarenal gland) • Adrenal gland located atop kidney • Shape, size and exact location vary depending on the species • Generally stimulated by ACTH Adrenal cortex (outer part) • Zonaglomerulosa • Mineralocorticoids (mainly aldosterone) • Na and K balance • Control loss of Na and K in the urine • Mineralocorticoids are not regulated by ACTH (regulated by renin-angiotensin system) • Sex hormones • Androgens, estrogens • Rate of secretion very low • Not necessary for normal reproductive behaviour and function

21. Adrenal glands

22. Adrenal gland Cap capsule C cortex Fzonafasciculata Gzonaglomerulosa M medulla Rzonareticularis Ttrabeculae V vein

23. Cross section of the adrenal gland showing the contrasting appearance of the cortex and medulla Magnification of boxed-I area in A that shows the different cell types associated with the the three zones of the cortex

24. Adrenal Gland • Glucocorticoids (cortisol and corticosterone) • - secreted by zonafasciulataand zonareticularis • - regulated by ACTH • - Stress ACTH glucocorticoids secretion • - absence of ACTH – atrophy of zonafasciulata and zonareticularis but not zonaglomerulosa

25. Seven adrenocortical hormones • Corticosterone • Cortisol • Cortisone • 11-dehydrocorticosterone • Glucocorticoids • 11- deoxycorticosterone • 17-hydroxy -11-deoxycorticosterone • Aldosterone • Mineralocorticoids

26. Structure of principle adrenocortical hormones

27. Role of glucocorticoids • Carbohydrate metabolism • Gluconeogenesis • From non-carbohydrate sources – protein and fat • Other two hormones – glucagon and epinephrine - increases blood glucose level by glycolysis of liver glycogen Use of glucocorticoids - treatment of bovine ketosis - anti-inflammatory activity - ophthalmic preparation, ear-drops, skin ointment

28. Mineralocorticoids (Aldosterone) • Secretion is regulated by • Renin-angiotensin system • Increased plasma concentration of potasium (hyperkalemia) • ACTH sitmulation (minor)

29. Renin-angiotensin system Renin - secreted by juxtaglomerula cells of the kidney Vascular endothelium form AngiotensinII Circulating blood globulin, angiotensinogen to form AngiotensinI Low blood pressure Aldosterone secretion (Zonaglomerulosa) - Systemic arteriolar vasoconstriction - Increase systemic blood pressure Promote Na reabsorption And retention of water

30. Mechanism of corticotropin (ACTH) on adrenocorticalsteroidogenesis. 1. Stimulation of the uptake of low-density lipoproteins (LDL), which are further processed to free cholesterol 2. Stimulation of the hydrolysis of stored cholesterol esters to generate free cholesterol 3. Stimulation of the transport of cholesterol into mitochondria, where cleavage of the cholesterol side chain occurs Promotion of the binding of cholesterol to the enzyme. AC, Adenylcyclase; ATP, adenosine triphosphate; cAMP, cyclic adenosine monophosphate; R, recaptor.

31. Mineralocorticoids (Aldosterone) • Actions • Increase sodium reabsorptionand potassium excretion from the kidney • Membrane transport in sweat glands, salivary glands, and intestinal mucosa • They also have some glucocorticoid activity

32. Adrenal medulla (inner part) • Chromaffin cells • Secrete amine hormones (catecholamines) • - Epinephrine & norepinephrine (fight –fright-flight) • - More epinephrine is secreted by adrenal medulla than norepinephrine • - Norepinephrine is also secreted by postganglionic sympathetic neurons • Activation of catecholamines – very fast • - half life of epinephrine - 20 to 40 seconds • - Medullary secretion – a continuous process and increases dramatically during an emergency

33. Catecholamines • Actions of epinephrine and norepinephrine are the similar • Differences depend on receptors • Adrenergic receptors - alpha receptors (stimulatory, but not intestinal mucosa) - beta receptors (inhibitory, but not cardiac muscle) • In addition to fight-fright-flight reactions of catecholamines, they have pronounced metabolic effect. - hyperglycemia, lypolysis, - calorigenic effect – increased muscle activity

34. Adrenal Insufficiency in man • Addison’s disease--hyposecretion of cortisol • Chronic adrenal insufficiency • Not common in man • Darkened skin (pigmentation) • Weight loss, • Hypoglycemia, increased K • Low BP • Metabolic acidosis • Inability to handle stress (impaired stress tolerance) • Dehydration and hypotension shock

35. Addison’ disease in animals Common in canines, not found in other animals Vomiting Diarrhoea, Lethargy Lack of appetite, Tremors or shaking, Muscle weakness, Low body temperature, Collapse, Low heart rate, and Pain in the hind quarters

36. Adrenal Insufficiency Sex hormone deficiency • Loss of body hair • Loss of libido or importancy • Menstrual and fertility disorders in women

37. Adrenal Insufficiency • Cushing’s syndrome • Cause: • - Sustained over-production of glucocorticoids by adrenal gland from ACTH by pituitary tumour • - Excessive glucocorticoid administration

38. Sex Steroids • HYPOTENSION • FLUID LOSS • HYPONATREMIA LAB: • Serum electrolytes: Decreased Na Increased K • Serum glucose • Adrenal hormone assay • Hydroxycorticoid & 17- ketosteroid in urine

39. Regulation of cortisol secretion by the hypothalamopituitary axis. Plus signs indicate stimulation; minus signs indicate inhibition. CRH, Corticotropin­releasing hormone.

40. ADRENAL GLAND

41. END OF LECTURE