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Endocrinology

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Location of parathyroid gland
one gland behind each of the upper and lower poles of the thyroid
Number of parathyroids
4: 2 upper and 2 lower
Size of parathyroids
6mm long, 3mm wide, 2mm thick
Macroscopic appearance of parathyroid
dark brown, resembles fat
Microscopic appearance of parathyroid
chief cells and oxyphil cells, capillary
What is the function of a chief cell?
secretes major amount of hormones
What is the function of an oxyphil cell?
Unknown
Structure of parathyroid hormone
Linear protein, 84 amino acids
Where is the biological activity of parathyroid hormone located
34 amino acids from N terminal
Major function of PTH
regulation and maintenance of a normal serum calcium level between 9-11mg%
Functions of calcium at a cellular level
1) Important in membrane permeability and electrical properties
2) Necessary for muscle contraction
3) Important as participant in hormone-target cell response
4) Important in clotting process
Hypocalcemia
level of calcium in body fluids is below normal, nervous system becomes more excitable
Hypercalcemia
level of calcium in body fluids is above normal
nervous system is depressed
muscles are sluggish and weak
decrease in QT interval of heart
Effect of PTH on bone absorption
Formation of new osteoclasts
Increased activity of osteoclasts
Mechanism of action of PTH
Cell receptors are coupled with G proteins
-Gs mediates stimulation of adenylyl cyclase and the production of cAMP which activates protein kinase A
-Gq stimulates phospholipase C to form second messengers inositol-triphosphate and diacylglycerol from phosphatidyl-insitol-biphosphate
Effect of PTH on membrane transport of Ca and PO4 (mitochondria)
Mitochondria takes in phosphate and releases calcium
Effect of PTH on membrane transport of Ca and PO4 (whole cell)
calcium is released
Hypoparathyroidism
Insufficient PTH secretion
Removal of parathyroids
Treatment of hypoparathyroidism
PTH used occasionally
Large quantities of vitamin D and calcium
Cause of hyperparathyroidism
usually a tumor
Result of hyperparathyroidism
Extreme osteoclastic activity
Rise in calcium level
Depression of nervous system
Muscle weakness
Constipation
Abdominal pain
Peptic ulcer
Lack of appetite
Depressed relaxation of heart during diastole
Renal stones
Eventual death
Copp experiment in 1961
Give dog perfusion of thyro-parathyroid glands with blood of high [Ca]
Results of Copp experiment
Systemic blood calcium level fell more rapidly than could be achieved by surgical thyro-parathyroidectomy
Conclusion of Copp experiment
Body provides another "factor" which aids in the control of calcium homeostasis, named it calcitonin
Where is calcitonin produced?
Produced by parafollicular cells in interstitium of thyroid gland
Structure of calcitonin
Polypeptide with 32 amino acids
Functions of calcitonin
Reduce plasma [calcium]
1) rapid decrease in activity of osteoclasts
2) increase in osteoblast activity
3) prevention of formation of new osteoclasts from progenitor cells
What controls the secretion of calcitonin?
Calcium levels in the blood
Location of the pancreas
Upper posterior portion of abdominal cavity
Lies horizontally behind stomach
Extends from duodenum to spleen
Microscopic anatomy of pancreas
Heterocrine, has two distinct types of glandular cells
Exocrine portion of pancreas
Contains tubulo-acinar secreting cells
Secretes pancreatic juice into duodenum via pancreatic duct
Endocrine portion of pancreas
Islets of Langerhans
Scattered glands of internal secretion
Islets of Langerhans
about 1 million islets in normal human adult
scattered about acini
twice as numerous in tail as in neck and body
Size of islets of Langerhans
75 by 150 microns
Weight of islets of Langerhans
about 1.5% of pancreas
Types of cells in the pancreas
Alpha cells
Beta cells
D cells
F cells
Alpha cells
Produce glucagon
Beta cells
manufacture, store, and secrete insulin
D cells
Produce somatostatin (SRIF)
F cells
Produce pancreatic polypeptide (PP)
1921 Banting and Best experiment
extracted first potent insulin, used in treatment of human diabetes
1956 Sanger work
determined amino acid sequence of insulin
1966 Dixon, Du, Katsoyannis, Zahn work
Synthesized human insulin
Structure of insulin
Polypeptide, 2 chains
A chain of insulin
21 amino acids, internal disulfide bridge
B chain of insulin
30 amino acids
Proinsulin
Precursor of insulin, discovered in 1968
Synthesized as single chain in beta cell with disulfide links formed
What stimulates the beta cell to release insulin?
Glucose is the most potent stimulus of insulin secretion and synthesis
Effects of insulin on liver
Glucose uptakes increased as well as storage as glycogen
Effects of insulin on glucose uptake and utilization and glycogen storage molecule
Greatly enhances storage of glycogen in skeletal muscle cells
Effects of insulin on fat metabolism in adipose cell
increased glucose transport into cell and utilization
inreased fat deposition (lipogenesis) and reduced release of fatty acids into body fluids
inhibition of lipase action in adipose cell
Effect of insulin on protein metabolism in cells
Facilitates movement of amino acids into cells
favors protein synthesis
Normal blood glucose concentration
90mg/100mL
Blood glucose concentration with a lack of insulin
300-1200mg/100mL
Blood glucose concentration with excess insulin
20-30mg/100mL
Type I diabetes
Insulin-dependent diabetes mellitus (IDDM)
decreased production and secretion of insulin
Type II diabetes
Non-insulin-dependent diabetes mellitus (NIDDM)
reduced sensitivity of target cells to insulin
Discovery of glucagon
1945-1052, deDuve, Sutherland, et al
Showed second polypeptide produced in islet cells of pancreas
Origin of glucagon
alpha cells of pancreas
Structure of glucagon
Linear polypeptide, 29 amino acids
Function of glucagon
Promotion of hepatic glycogensis, mobilization of fatty acids and glycerol from adipose tissue
Location of adrenal gland
Posterior surface of abdominal cavity, behind peritoneum
Shape of adrenal gland
Right- pyramidal
Left- crescent shaped
Structure of adrenal gland
Cortex
Medulla
Structure of cortex of adrenal gland
Yellow, derived from mesoderm
Structure of medulla of adrenal gland
Reddish-brown, derived from ectoderm of neural crest
Zones of cortex of adrenal gland
Zona glomerulosa
Zona fasciculata
Zona reticularis
Zona glomerulosa
Produces mineralocorticoids
Zona fasciculata
Produces glucocorticoids
Zona reticularis
Produces sex hormones
What does the medulla of the adrenal gland produce
Epinephrine
Mineralocorticoid
Aldosterone
Aldosterone effect on collecting duct
Reabsorption of sodium
Secretion of hydrogen
Secretion of potassium
Aldosterone and its effect on reabsorption of sodium
Aldosterone increases -> sodium reabsorption increases -> mild hypernatremia (blood becomes hypertonic) -> thirst -> polydipsia -> normal sodium concentration restored
Aldosterone and its effect on secretion of hydrogen
Aldosterone increases -> hydrogen ion secretion into urine increases -> alkalosis in body fluids increases (higher alkalinity)
Aldosterone and its effect on secretion of potassium
Aldosterone increases -> potassium ion secretion increases -> hypokalemia (in body fluids) -> increase in resting membrane potential -> reduction in membrane excitability -> paralysis
Systemic effects of increased aldosterone secretion
Hypertension and edema
Glucocorticoid
Cortisol
General effects of cortisol
affects glucose metabolism and other organic nutrients
facilitates body's response to stress
Special effects of cortisol
carbohydrate metabolism
protein metabolism
fat metabolism
blocks inflammatory response
aids in adaptation to stress
Cortisol's effect on carbohydrate metabolism
Stimulates gluconeogenesis by liver
decreases glucose use by cells
Cortisol's effect on protein metabolism
Mobilizes amino acids from tissues
in liver, increased rate of deamination of amino acids and increased protein synthesis
Cortisol's effect on fat metabolism
mobilizes fatty acids from adipose tissue
Adrenal sex hormones
Androgens, progesterone, and estrogens
Androgens in adrenal gland
Several moderately active male sex hormones
-androstenedione
-dehydroepiandrosterone (DHEA)
Progesterone and estrogens in adrenal gland
secreted in minute amounts