Parathyroid gland

Parathyroid glands are small endocrine glands in the neck of humans and other tetrapods. Humans usually have four parathyroid glands, located on the back of the thyroid gland in variable locations. The parathyroid gland produces and secretes parathyroid hormone in response to a low blood calcium, which plays a key role in regulating the amount of calcium in the blood and within the bones.

Parathyroid glands share a similar blood supply, venous drainage, and lymphatic drainage to the thyroid glands. Parathyroid glands are derived from the epithelial lining of the third and fourth pharyngeal pouches, with the superior glands arising from the fourth pouch and the inferior glands arising from the higher third pouch. The relative position of the inferior and superior glands, which are named according to their final location, changes because of the migration of embryological tissues.

Hyperparathyroidism and hypoparathyroidism, characterized by alterations in the blood calcium levels and bone metabolism, are states of either surplus or deficient parathyroid function.

1. Parathyroid Gland

2. Organisation 4 tiny parathyroid glands, in the neck, on the posterior surface of the thyroid gland. Have 2 supiriorly & 2 infiriorly. Small in size, measuring about 6 mm long, 3 mm wide and 2 mm thick with dark brown colour

3. Histology ➤ Made up of chief cells & oxyphil cells Chief cells ➤ secrate parathormone Oxyphil cells ➤ degenerated chief cells and their function is unknown ➤ may secrate parathormone during physiological condition called parathyroid adenoma

4. Parathormone ➤ secreted by the chief cells of the parathyroid glands ➤ essential for the maintenance of blood calcium level within a very narrow critical level ➤ maintenance of blood calcium level is necessary because calcium is an inorganic ion for many physiological functions

5. ➤ Chemistry ➤ Parathormone is protein in nature, having 84 amino acids ➤ It’s Molecular weight in 9,500 ➤ Half life & Plasma level ➤ Parathormone has a half-life of 10 minutes ➤ Normal plasma level of PTH is about 1.5-5.5 mg/dL

6. Actions of PTH on Blood Calcium Level ➤ Primary action of the PTH is to maintain the blood calcium level within the critical range of 9-11 mg/dL ➤ PTH control blood calcium level by 1. Reabsorption of Ca from Bones 2. Reabsorption of Ca from renal tubules (Kidney) 3. Absorption of Ca from Gastrointestinal tract

7. ➤ On bones > PTH enhances the reabsorbtion of Ca from the bones by acting on osteoblasts and osteoclasts of the bone > Increase the number and activity of osteoclasts (bone destroying cells). > Increased collagen synthesis > Increased alkaline phosphatase activity > Increased local growth factors: IGF and transforming factors

8. ➤ On Kidney > PTH increases the reabsorbtion of Ca from the renal tubules along with magnesium ions and hydrogen ions > Increases Ca reabsorbtion mainly from distal convoluted tubule and proximal part of collecting duct > PTH also increases the formation of 1, 25-di-hydroxycholecalciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys > Decreased phosphate, sodium and bicaronate reabsorbtion from the proximal tubule

9. ➤ On Gastrointestinal Tract > PTH increases the absorption of Ca ions from the GI tract indirectly. > The activated vitamin D is very essential for the absorption of Ca from the GI tract > PTH also increase the absorption of PO4 & mg

10. Role of Ca ion in regulating 1,25-Dihydroxycholecalciferol > When blood Ca level Increases, it inhibits the formation of 1,25- Dihydroxycholecalciferol. The mechanism involved in the inhibition of the formation of 1,25-Dihydroxycholecalciferol as folows Increase in Ca ion concentration directly suppresses of 25-Dihydroxycholecalciferol into 1,25-Dihydroxycholecalciferol Increase in Ca ion concentration decreases the PTH secretion which in turn suppresses the convertion of 25-Dihydroxycholecalciferol into 1,25-Dihydroxycholecalciferol

11. Blood level of Calcium Increase in blood calcium level decreases PTH secretion Parathormone secretion is inversely proportional to blood calcium level Conditions when PTH secretion decreases are : > excess quantities of calcium in the diet > increased vitamin D in the diet > increased reabsorbtion of Ca from the bones

12. Disorders of Parathyroid Gland

13. Hypoparathyroidism ➤ Characterized by: Hypocalcaemia Increase neuro-muscular excitability (tetany) ➤ Mechanism: ➤ Decrease plasma Ca 2+ ions < 9 mg/dl Increase the excitability of Nervous system due to ↑ neuronal membrane permeability to Na + Hyperexcitable nerve fibres, spontaneously initiate nerve impulses to peripheral sk ms thus eliciting tetanic contraction.

14. Tetany Manifested by ↑ed neuromuscular excitability due to ↓ plasma ionized Ca 2+ Causes: a) Hypoparathyroidism b) Alkalaemia, decrease the solubility product of Ca 2+ & PO 4 and leads to reduced ionized Ca 2+ . precipitation of CaPO 4 ;

15. c) Decreased Ca 2+ absorption from the intestine: 1. Low calcium intake. 2. Excess intake of antiacids (peptic ulcer) lead to Ca 2+ precipitation and decreased absorption. 3. Steatorrhea (fatty diarrhea), where Ca 2+ is lost in stools.0

16. Manifestation of Tetany These depend on the degree of ↓ed blood Ca 2+ level: 1. Manifest tetany: Blood Ca 2+ level is below 7 mg% (N 9-11 mg%). Muscular spasms in the hands and feet (Carpo-pedal spasm). 2. Latent tetany: Blood Ca 2+ level is at 7-9 mg%, Muscle spasms only occur when the patient is exposed to stress.

17. Treatment of Tetany 1. IV injection of Ca 2+ gluconate during ms spasm. stops immediately the tetanic spasms. 2. Calcium level is then maintained by: giving vitamin D and administration of oral calcium. 3. Acidifying salts as ammonium chloride help Ca 2+ absorption as they increase the ionization of Ca 2+ .

18. 4. In hypoparathyroidism: Repeated administration of parathormone leads to formation of antihormone which antagonizes its action. A synthetic steroid ‘dihydrotachysterol (or AT 10)’ Has similar effects as parathormone and vitamin D, Not produce antihormone.

19. Islets of Langerhans of Pancreas

20. Pancreas A triangular gland, which has both exocrine and endocrine cells, located behind the stomach Strategic location Acinar cells produce an enzyme-rich juice used for digestion (exocrine product) Pancreatic islets ( islets of Langerhans ) produce hormones involved in regulating fuel storage and use.

21. Islets of Langerhans 1 million islets 1-2% of the pancreatic mass Beta ( β ) cells produce insulin Alpha ( α ) cells produce glucagon Delta ( δ ) cells produce somatostatin F cells produce pancreatic polypeptide

22. Insulin Hormone of nutrient abundance A protein hormone consisting of two amino acid chains linked by disulfide bonds Synthesized as part of proinsulin (86 AA) and then excised by enzymes, releasing functional insulin (51 AA) and C peptide (29 AA).

23. Insulin Structure 1- Large polypeptide 51 AA (MW 6000) 2- Tow chains linked by disulfide bonds. A chain (21 AA) B chain (30 AA) 3- disulfide bonds.

24. Regulation of Insulin Secretion No insulin is produced when plasma glucose below 50 mg/dl Half-maximal insulin response occurs at 150 mg/dl A maximum insulin response occurs at 300 mg/dl Insulin secretion is biphasic: Upon glucose stimulation– an initial burst of secretion (5-15 min.) Then a second phase of gradual increment that lasts as long as blood glucose is high

25. Insulin secretion is biphase

26. Insulin Action on Cells Insulin is the hormone of abundance. The major targets for insulin are: liver Skeletal muscle adipose tissue The net result is fuel storage

27. Insulin Action on Carbohydrate Metabolism Liver: Stimulates glucose oxidation Promotes glucose storage as glycogen Inhibits glycogenolysis Inhibits gluconeogenesis Muscle: Stimulates glucose uptake (GLUT4) Promotes glucose storage as glycogen

28. Adipose Tissue: Stimulates glucose transport into adipocytes Promotes the conversion of glucose into triglycerides and fatty acids

29. Glucagon A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent Produced by α cells in the pancreas Its major target is the liver, where it promotes: Glycogenolysis – the breakdown of glycogen to glucose Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates Release of glucose to the blood from liver cells

30. Physiological Action of Glucagon Stimulates glycogenolysis, gluconeogenesis & inhabits glycogenesis Promotes lepolysis & ketogenesis Increases calorigenesis

31. Somatostatin Secreted from D cells of pancreas Also secreted from hypothalamus & GIT A peptide hormones with 2 forms, one with 14 AAs & the other with 28 Aas Functions ➤ inhibits secretion of insulin & glucagon ➤ inhibits GI motility & GI secretions ➤ regulates feedback control of gastric emptying

32. Diabetes Mellitus (DM) A serious disorder of carbohydrate metabolism Results from hyposecretion or hypoactivity of insulin The three cardinal signs of DM are: Polyuria – huge urine output Polydipsia – excessive thirst Polyphagia – excessive hunger and food consumption

33. Diabetes Mellitus Type l Type 1: beta cells destroyed- no insulin produced  chronic fasted state, "melting flesh", ketosis, acidosis, glucosurea, diuresis & coma

34. Diabetes Mellitus Type ll Over 15 million diabetics in USA- 10% type I, 90% type II More common is some ethnic groups Insulin resistance keeps blood glucose too high Chronic complications: atherosclerosis, renal failure& blindness

35. Symptoms of Diabetes Mellitus ➤ Hyperglycemia ➤ Polyuria ➤ Polydipsia ➤ Polyphagia ➤ Ketoacidosis ➤ Hyperlipidemia ➤ Muscle wasting ➤ Electrolyte depletion

36. Diagnosis Demonstrating persistence hyperglycemia & glycosuria Glucose Tolerance Test (GTT) – oral is preferred Estimation of Fasting Blood Glucose (FBG) FBS more than 126 mg% inmore than two occasions confirms DM

37. Treatment Insulin therapy Oral hypoglycemic agents Life style modifications