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

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