1. Suprarenal gland:
The two adrenal glands, lie at the superior poles of the two kidneys, each gland is composed of two distinct parts, the adrenal medulla and the adrenal cortex.

2. The adrenal medulla, the central part of the gland, is functionally related to the sympathetic nervous system; it secretes the hormones epinephrine and norepinephrine in response to sympathetic stimulation.

3. The adrenal cortex (the outer part) secretes an entirely different group of hormones, called corticosteroids. These hormones are:
1-Mineralocorticoids: they have gained this name because they especially affect the electrolytes (the “minerals”) of the extracellular fluids-sodium and potassium, in particular.

4. 2-The glucocorticoids have gained their name because they exhibit important effects that increase blood glucose concentration.
Approximately 90 to 95 per cent of the cortisol in the plasma binds to plasma proteins
. About 2% is in the free form which is the active form .This high degree of binding to plasma proteins slows the elimination of cortisol from the plasma; therefore, cortisol has a relatively long half life (the bound cortisol act as a reservoir for the hormone )
3-Sex hormones.

5. Functions of the Glucocorticoids:
At least 95 per cent of the glucocorticoid activity of the adrenocortical secretions results from the secretion of cortisol,
Cortisol:
The physiological action of cortisol:
1-Effects of Cortisol on Carbohydrate Metabolism:
It increases blood glucose concentration(antihypoglycemic effect) .

6. a-It stimulates gluconeogenesis (formation of carbohydrate from proteins and some other substances) by the liver, this effect is part of the effect on protein ,because it increases the enzymes required to convert amino acids into glucose in the liver cells. As a result, more amino acids become available in the plasma to enter into the gluconeogenesis process of the liver and thereby to promote the formation of glucose.

7. The increase in glucose level will stimulate insulin secretion; also it reduces the sensitivity of many tissues, especially skeletal muscle and adipose tissue, to the stimulatory effects of insulin on glucose uptake and utilization. If this persists for long time it will cause B cell exhaustion →diabetes mellitus.

8. b- Decreased Glucose Utilization by Cells: Cortisol causes a moderate decrease in the rate of glucose utilization by most cells in the body (skeletal , muscles and adipose tissue) ,by inhibiting glucose entry to the cells→ increase blood glucose concentration to be available for normal brain function ,so it protect the brain from hypoglycemia.

9. 2-Effect on protein metabolism: It exerts catabolic effect on protein
2-Effect on protein metabolism: It exerts catabolic effect on protein. Because of decreased amino acid transport into extrahepatic tissues also depresses the formation of RNA and subsequent protein synthesis in many extrahepatic tissues, especially in muscle and lymphoid tissue. It diverts amino acids from the muscles and the liver for the process of deamination and gluconeogenesis, so it facilitates the breakdown of proteins.

10. 3-Effects of Cortisol on Fat Metabolism:
It promotes mobilization of fatty acids from adipose tissue. This increases the concentration of free fatty acids in the plasma, which also increases their utilization for energy.

11. 4-Effect on minerals: It has a similar effect to aldosterone, although it is weaker than it (1/10 the power of Aldosterone). It promotes sodium retention and potassium elimination, but no edema because there is increase in the glomerular filtration rate (GFR).

12. 5-Effect on respiration: It is important for the synthesis of surfactant during intrauterine life (to prevent respiratory distress syndrome). In females who are about to deliver preterm babies we usually give them cortisol to promote the formation of surfactant)

13. 6-Effect on water balance:
It causes sodium retention which leads to water retention .It also causes increase in GFR (glomerular filtration rate), which counteract the water retention and the person does not develop edema.

14. 7-Effect on cardiovascular system: Cortisol restores vascular reactivity. It helps in maintaining arterial response to sympathetic tone. Deficiency of the hormone leads to hypotensive subject due to failure to maintain the peripheral resistance. While patients with hyperfunction of the adrenal cortex are hypertensive(because of the increase in peripheral resistance).

15. 8-Effect on GIT:
Cortisol reduces the resistance of gastric mucosa to HCL so increase secretion of it leads to ulcer (so before giving the patient steroid tablets ask him if he has gastric pain or ulcer otherwise it may cause perforation to the stomach). Also it has an anti vitamin D effect .It prevent the absorption of the vitamin from the intestine.

16. 9-Effect on lymphoid tissue and heamopoiesis:
Cortisol suppresses the production of antibodies (used in chronic inflammatory diseases) in which inappropriate antibodies are produced in the subject against his own tissues .
The administration of large doses of cortisol causes decreases the output of both T cells and antibodies from the lymphoid tissue. As a result, the level of immunity for almost all foreign invaders of the body is decreased).
Conversely, this ability of cortisol and other glucocorticoids to suppress immunity makes them useful drugs in preventing immunological rejection of transplanted hearts, kidneys, and other tissues.

17. 10-Effect on bones:
Excessive secretion leads to osteoporosis due to destruction of the matrix of the bone (catabolic effect of cortisol on protein found in the matrix). This effect of cortisol in mobilizing proteins could make amino acids available to needs of the cells to synthesize substances essential to life.

18. 11-Anti- inflammatory effect of cortisol: It has the following effects to prevent inflammation: 1-Cortisol stabilizes the lysosomal membranes, so decreases the proteolytic enzymes that are released by the lysosomes. 2. Cortisol decreases the permeability of the capillaries. This prevents loss of plasma into the tissues. 3. Cortisol decreases both migration of white blood cells into the inflamed area and phagocytosis of the damaged cells. 4. Cortisol suppresses the immune system, causing lymphocyte reproduction to decrease markedly(especially T lymphocytes). 5. Cortisol attenuates fever mainly because it reduces the release of interleukin-1 from the white blood cells. So it can be used in disease that are characterized by severe local inflammation like rheumatoid arthritis, rheumatic fever, and acute glomerulonephritis.

19. 12-Effect on allergy: It blocks the inflammatory response to allergic reactions in the same way that it blocks the other types of inflammatory response. 13-Effect on blood: It decreases the number of eosinophils and lymphocytes in the blood. It also increases the production of red blood cells (mechanisms unclear). When excess cortisol is secreted by the adrenal glands, polycythemia often results, and conversely, when the adrenal glands secrete no cortisol, anemia often results.

20. Mineralocorticoids:
They are secreted by the adrenal cortex ,the most important is Aldosterone which increases the reabsorption of Na from the tubules of the kidney ,salivary ,sweat ,gastric and intestinal glands ,so it elevates the level of sodium in blood while K level is eliminated in the opposite direction.

21. Mineralocorticoids: Control of aldosterone secretion:
The release of aldosterone is under the influence of:
1-The level of K and Na in plasma:
the increased level of K and the reduction in Na level will cause stimulation of aldosterone secretion (direct effect on the adrenal gland).

22. 2-Heamorhage and hypovolemia: This result in decrease in venous return decrease in cardiac output → pressure in afferent arterioles in the kidney is reduced →stimulation of juxtaglomerular apparatus in the kidney →release of renin which acts on angiotensinogen, and convert it to angiotensin I . During its passage to the capillaries of the lung converted to angiotensin II by converting enzyme secreted by the endothelial lining of the blood vessel of the lung. Angiotensin II 1- increases the peripheral resistance and 2- it has direct stimulation to the adrenal cortex to release aldosteron→ Na retention and K elimination as a result we have increase in the blood pressure

23. Clinical conditions related to the adrenal gland disturbances:
1-Hyperadrenalism-Cushing’s Syndrome
Hypersecretion by the adrenal cortex (or prolonged exposure to high level of steroids) causes a complex cascade of hormone effects called Cushing’s syndrome.
The cause for this abnormality is either:
ACTH dependent causes :
Increase of ACTH →↑ cortisol level. As I case:
1-Tumor (like adenoma) of the anterior pituitary.
2-Abnormal function of the hypothalamus that causes high levels of corticotropin-releasing hormone (CRH),
3-“ectopic secretion” of ACTH by a tumor elsewhere in the body, such as an abdominal carcinoma;
When Cushing’s syndrome is secondary to excess secretion of ACTH by the anterior pituitary, this is referred to as Cushing’s disease.

24. 2-Non- ACTH dependent causes:
1-Adrenocortical hyperplasia.
2-Adenoma of the adrenal cortex.( Primary overproduction of cortisol by the adrenal glands is usually associated with reduced ACTH levels due to cortisol feedback inhibition of ACTH secretion by the anterior pituitary gland).
3-Iatrogenic : administration of large amounts of synthetic glucocorticoid ,as in case of asthma, skin diseases and renal disorder.

25. Symptoms of Cushing’s disease: 1-Effects on Carbohydrate Metabolism: Increased blood glucose concentration. May cause diabetes mellitus. 2-The effects of glucocorticoids on protein: Protein catabolism is often profound in Cushing’s syndrome, causing greatly decreased tissue proteins almost everywhere in the body. Severe muscles weakness and wasted thin limbs. Skin atrophy (bruises) and osteoporosis of the bones (back pain).

26. The loss of protein synthesis in the lymphoid tissues leads to a suppressed immune system, so that many of these patients die of infections. Also because of loss of protein in the subcutaneous tissues, they tear easily, resulting in development of large purplish striae in the skin.

27. 3-The most striking feature of the disease: Buffalohamp : mobilization of fat from the lower part of the body and abnormal deposition of fat in the lower part of the neck, the thoracic and upper abdominal regions. Moon face Increase of Na and water retention. Excessive secretion of sex hormone acne, hirsutism (excess growth of hair on the face). About 80 per cent of patients have hypertension, presumably because of the slight mineralocorticoid effects of cortisol.

29. Hypofunction of the adrenal cortex: Hypoadrenalism-Addison’s Disease: Primary →tumor in the adrenal gland Addisson's disease. Secondary→ reduction of the ACTH secretion due to pituitary or hypothalamic disorder. The causes of Addisson's disease: Autoimmune disease: antigene –antibody reaction. Tuberculosis or invasion of the adrenal cortices by cancer →destruction of the gland. The symptoms partly due to aldosteron deficiency but mainly due to glucocorticoid deficiency.

30. Symptoms of Addisson's disease:
1-Mineralocorticoid Deficiency:
Sodium ions, chloride ions, and water are lost into urine in great amounts while K is preserved. The net result is a greatly decreased extracellular fluid volume which leads to hypotension. Cardiac output decreases, and the patient dies in shock if not treated.
2-Glucocorticoid Deficiency:
Hypoglycemia due to reduction of gluconeogenesis. It reduces the mobilization of both proteins and fats from the tissues, thereby depressing many other metabolic functions of the body.

31. Melanin Pigmentation: pigmentation of the mucous membranes and skin
Melanin Pigmentation: pigmentation of the mucous membranes and skin. Especially of the area that is already pigmented exposed to light e.g. face, neck, back of the neck, hand, elbow ,knee. Also mucus membrane like lips, eyelids and vagina.

32. The cause of pigmentation is as follows: When cortisol secretion is depressed, the normal negative feedback to the hypothalamus and anterior pituitary gland is also depressed, therefore allowing tremendous rates of ACTH secretion as well as simultaneous secretion of increased amounts of MSH. Probably the tremendous amounts of ACTH cause most of the pigmenting effect because they can stimulate formation of melanin by the melanocytes in the same way that MSH does ↓ ↓ This is like MSH ↑ All the activity of the ACTH is due to this limit

33. Addisonian Crisis. Great quantities of glucocorticoids are occasionally secreted in response to different types of physical or mental stress. In a person with Addison’s disease, at rest the patient is normal but the output of glucocorticoids does not increase during stress. Yet whenever different types of trauma, disease, or other stresses, such as surgical operations, a person is likely to have an acute need for excessive amounts of glucocorticoids and often must be given more than the normal quantities of glucocorticoids to prevent death. This critical need for extra glucocorticoids and the associated severe debility in times of stress is called an addisonian crisis, in which GIT symptoms happen and acute abdominal pain, and hypotension . We have to correct it rapidly by dexamethazol injection.

34. The crises happens sometimes in cases like asthma we give the patients high doses of cortisol, so we have suppression of the activity of the adrenal gland, when stop giving the drug we have to stop it gradually not suddenly to avoid Addissonian crises.

35. Adrenal medulla:
This gland secretes adrenalin and noradrenalin (catecholamine), it is not under the control of pituitary gland or hypothalamus, but it is controlled by the autonomic nervous system so the hormones are called the hormones of emergency. The quantity of adrenalin is about 4-5 times as much as that of noradrenalin The metabolic effect of catecholamine is mainly due to the effect of adrenalin rather than noradrenalin these effects include: A-Increase the glucose level in the blood by: 1- stimulation of gluconeogenesis. 2-Inhibiting the release of insulin. B-Increase the level of free fatty acids in blood so it is concerned as a ketogenic factor.

36. These effects of the hormones in various tissues are grouped according to the receptors with which they interact .We have 2 groups:
-Alpha receptors serve excitatory function as vasoconstriction.
-Beta receptors: serve predominantly inhibitory function as vasodilatation and bronchodiltation.
Except the effect on the heart → increase the force of concentration→ increase cardiac output→ increase systolic blood pressure→ increase pulse pressure.

37. Adrenalin causes tachycardia with an increase in cardiac output and a fall in the peripheral resistance, so we have increase in systolic blood pressure and a drop in the diastolic pressure, increase in pulse pressure. Noradrenaline increase the total peripheral resistance while adrenalin causes vasoconstriction in splanchnic areas and dilatation of skeletal muscle blood vessels→ decrease in peripheral resistance→ decrease in blood pressure.

38. The clinical conditions result from disturbances of the release of catecholamins: Pheochromocytoma a tumor of the adrenal medulla → increase secretion of catecholamins continuously or periodically (in young age mainly years old). Increase in blood pressure →decrease diastolic pressure→ increase in pulse pressure. This case is associated with flushing, sweating (perspiration), palpitation or tachycardia, tremor of the hand and the patient may have headache. Estimation of adrenalin and noradrenalin is done through the estimation of their metabolites in urine which is called venyl mandillic acid (VMA).

39. The pancreas
It lies in the abdominal cavity in the concavity of the duodenum, it has both endocrine and exocrine functions .The endocrine function is limited to the islets of langerhans which are distributed in the tail more than in the body and head. It forms 2% of the pancreatic tissue

40. The types of cells in the islet of langerhans are: Beta cells: 60 per cent of all the cells of the islets, lie mainly in the middle of each islet and secrete insulin and amylin. The alpha cells, about 25 per cent of the total, secrete glucagon. The delta cells, about 10 percent of the total, secrete somatostatin. The PP cell is present in small numbers in the islets and secretes a hormone of uncertain function called pancreatic polypeptide. Insulin inhibits glucagon so there is connection between these cells so each one inhibits the other. Amylin inhibits insulin secretion, Somatostatin inhibits both insulin and glucagon.

41. 1)Alpha cells: they secrets glucagon which are polypeptides of 29 amino acids, has several functions that are diametrically opposed to those of insulin its effects are:
1-Glucagon Causes Glycogenolysis and Increased Blood Glucose Concentration. Breakdown of liver glycogen.
2-Glucagon Increases Gluconeogenesis. Increase the rate of amino acid uptake by the liver cells and then the conversion of many of the amino acids to glucose by gluconeogenesis.
3-Increase ketogenesis.
4-Glucagon activates adipose cell lipase, making increased quantities of fatty acids available to the energy systems of the body. Glucagon also inhibits the storage of triglycerides in the liver, which prevents the liver from removing fatty acids from the blood; this also helps make additional amounts of fatty acids available for the other tissues of the body.
fact the physiological importance of glucagon is mainly in fasting conditions when energy substrates in blood need to be maintained.

42. Regulation of Glucagon Secretion
1-Increased Blood Glucose Inhibits Glucagon Secretion.
In hypoglycemia, glucagon is secreted in large amounts; it then greatly increases the output of glucose from the liver and thereby serves the important function of correcting the hypoglycemia and protecting the brain from damage by hypoglucemia. Stimulation of the sympathetic system stimulates glycogen and inhibits insulin secretion. So using of adrenergic blocking drugs in hypoglycemia partially inhibits the release of glucagon.

43. 2-Increased Blood Amino Acids Stimulate Glucagon Secretion:
High concentrations of amino acids, as occur in the blood after a protein meal (especially the amino acids alanine and arginine), stimulate the secretion of glucagon. This will convert amino acids to glucose making more glucose available to tissues.

44. 3- Exercise Stimulates Glucagon Secretion
3- Exercise Stimulates Glucagon Secretion. In exhaustive exercise, the blood concentration of glucagon often increases fourfold to fivefold. A beneficial effect of the glucagon is that it prevents a decrease in blood glucose. One of the factors that might increase glucagon secretion in exercise is increased circulating amino acids. The level of blood glucose is kept constant by adjustment of the level of glycogen and insulin.

45. 2) Beta cells: they secret insulin which is a protein composed of 2 chains connected by disulfide Bridge. When insulin is secreted into the blood, it circulates almost entirely in an unbound form;, and some insulin is bound to B-globulin.

46. 1-Effect of Insulin on Carbohydrate Metabolism: Insulin increases glucose transport (membrane permeability) into and glucose usage by most other cells of the body (with the exception of the nerve cells, brain cells, intestinal mucosa renal tubules, and red blood cells ).The target tissue for insulin's action is the skeletal muscle and liver.

47. -Effect on the muscle: During much of the day, muscle tissue depends not on glucose for its energy but on fatty acids. The principal reason for this is that the normal resting muscle membrane is only slightly permeable to glucose, except when the muscle fiber is stimulated by insulin. However, under two conditions the muscles do use large amounts of glucose. One of these is during moderate or heavy exercise. This usage of glucose does not require large amounts of insulin, because exercising muscle fibers become more permeable to glucose even in the absence of insulin because of the contraction process itself.

48. The second condition for muscle usage of large amounts of glucose is during the few hours after a meal. At this time the blood glucose concentration is high and the pancreas is secreting large quantities of insulin. This glucose which enters the cell is used to supply energy and the excess is stored in the form of glycogen.

49. 3-Effect on the liver: -Insulin promotes the glucose uptake by hepatocytes→ activates glycogen synthetase→ synthesis of glycogen from glucose. -Insulin also inhibits gluconeogenesis.

50. 4- Effect on fat: Insulin increases the utilization of glucose by most of the body’s tissues, which automatically decreases the utilization of fat, thus functioning as a fat sparer. However, insulin also promotes fatty acid synthesis in hepatocytes. Insulin inhibits the action of hormone-sensitive lipase (hydrolyse TG into glycerol and fatty acids)→ no hydrolysis of triglycerides (TG and lipoproteins will be stored in the adipose tissues). Insulin promotes glucose transport through the cell membrane into the fat cells. So insulin promotes lipogenesis and inhibits lipolysis.

51. In case of insulin deficiency, All aspects of fat breakdown and use for providing energy are greatly enhanced because of decreased utilization of glucose. What happens is Lipolysis of storage fat and release of free fatty Acids. The most important effect is that the enzyme hormone-sensitive lipase in the fat cells becomes strongly activated. This causes hydrolysis of the stored triglycerides, releasing large quantities of fatty acids and glycerol into the circulating blood.

52. Increases plasma cholesterol and phospholipid concentrations.
Insulin deficiency also promotes liver conversion of some of the fatty acids into phospholipids and cholesterol, which promotes the development of atherosclerosis in people with serious diabetes (decrease blood supply to tissues → diabetic nephropathy or retinopathy, increase liability for myocardial infarction and increase the liability for cerebrovascular accidents).

53. Excess usage of fats during insulin lack causes ketosis and acidosis
Insulin lack also causes excessive amounts of acetoacetic acid to be formed in the liver cells. Some of the acetoacetic acid is also converted into acetone. Both are called ketone bodies. So in severe diabetes these can cause severe acidosis and coma, which often leads to death.

54. -Effect on proteins: Insulin Promotes Protein Synthesis and Storage via 1. Insulin stimulates transport of many of the amino acids into the cells (so in insulin lack there will be urea excretion in the urine). 2. Insulin increases the translation of messenger RNA. 3- Increases the rate of transcription of selected DNA genetic sequences. 4. Insulin inhibits the catabolism of proteins 5. In the liver, insulin depresses the rate of gluconeogenesis. This suppression of gluconeogenesis conserves the amino acids in the protein stores of the body. In summary, insulin promotes protein formation and prevents the degradation of proteins. So In severe diabetes mellitus, there will be extreme weakness of the body. Insulin and Growth Hormone Interact Synergistically to Promote Growth.

55. 6-Effect on potassium:
Under the effect of insulin, the level of blood potassium decreased because insulin causes mobilization of K from blood to cells.
So in case of renal failure we have uremia increased level of potassium in the extracellular fluid, so we use insulin to promote K entry to the cell.

56. Clinical conditions resulting from disturbances in insulin secretion: Diabetes mellitus is a syndrome of impaired carbohydrate, fat, and protein metabolism caused by either lack of insulin secretion or decreased sensitivity of the tissues to insulin, in which there is increase in blood glucose level . There are two general types of diabetes mellitus: 1-Type I diabetes, also called insulin-dependent diabetes mellitus (IDDM), and is caused by lack of insulin secretion. Injury to the beta cells of the pancreas or diseases that impair insulin production can lead to type I diabetes. Viral infections or autoimmune disorders may be involved in the destruction of beta cells in many patients with type I diabetes, although heredity also plays a major role, therefore it may occur in children (juvenile type), The usual onset of type I diabetes occurs at about years of age, the body weight either reduced or normal.

57. 2-Type II diabetes, also called non–insulin-dependent diabetes mellitus (NIDDM), and is caused by decreased sensitivity of target tissues to the metabolic effect of insulin. This reduced sensitivity to insulin is often called insulin resistance (although high level of insulin → decrease action). It is far more common than type I, accounting for about 90 per cent of all cases of diabetes mellitus. In most cases, the onset of type II diabetes occurs after age 30, often between the ages of 50 and 60 years. Therefore, this syndrome is often referred to as adult-onset diabetes. It happens mainly in obese people, because some studies suggest that there are fewer insulin receptors, in obese than in lean subjects. In addition to obesity there are other causes of insulin resistance like Cushing’s syndrome, Acromegaly, Polycystic ovary disease, and others.

58. Symptoms associated with diabetes mellitus:
1-Polyuria and glucosuria: The high blood glucose causes more glucose to filter into the renal tubules than can be reabsorbed, and the excess glucose spills into the urine. This normally occurs when the blood glucose concentration rises above 180 mg/100 ml, a level that is called the blood “threshold” for the appearance of glucose in the urine. The very high levels of blood glucose can cause severe cell dehydration throughout the body. This occurs partly because glucose does not diffuse easily through the pores of the cell membrane, and the increased osmotic pressure in the extracellular fluids causes osmotic transfer of water out of the cells. In addition to the direct cellular dehydrating effect of excessive glucose, the loss of glucose in the urine causes osmotic diuresis→(polyuria) (excessive urine excretion),.

59. 2- Polydepsia: As a result of intracellular and extracellular dehydration, there will be increased feeling of thirst, because of stimulation of thirst center in the hypothalamus. . 3-Polyphagia: Increased consumption of food as a result of glucose loss. There are 2 centers in the hypothalamus, the appetite center and the satiety center which is affected by insulin (not like the other parts on nervous system which are not affected by insulin as we mentioned).

60. 4-Weight loss: Failure of glucose and protein metabolism by the body causes loss of weight despite eating large amounts of food (polyphagia). Note: Loss of weight occurs in both thyrotoxicosis and diabetes mellitus; we differentiate between them by measuring glucose and thyroxin

61. 5 -Ketosis: The shift from carbohydrate to fat metabolism in diabetes increases the release of keto acids, ( acetoacetic acid and b-hydroxybutyric acid), into the plasma more rapidly than they can be taken up and oxidized by the tissue cells. As a result, the patient develops severe metabolic acidosis from the excess keto acids (keton bodies), which, in association with dehydration due to the excessive urine formation (because they are highly osmotic molecules, move water from the intracellular to extracellular fluid), can cause severe acidosis. This leads rapidly to diabetic coma and may be death if not treated immediately with insulin.

62. There will be rapid and deep breathing (kassmaul breathing), which causes increased expiration of carbon dioxide; this buffers the acidosis but also depletes extracellular fluid bicarbonate stores. The kidneys compensate by decreasing bicarbonate excretion and generating new bicarbonate that is added back to the extracellular fluid.

63. 6-Ionic (electrolytes imbalance):
a-Potassium level increased because it moves from the intracellular fluid to extracellular).
b-Sodium level decreased because it is excreted in urine.
c-Chloride accompanies sodium so it decreases.

64. 7-Infection:
People with DM are liable for infection because of electrolyte imbalance and because glucose is a good culture media for the growth of bacteria (so in any intervention of the body like surgery, we have to be aware of the presence of DM to use antibiotics, may be higher doses).

65. Diagnosis of diabetic patients: The usual methods for diagnosing diabetes are based on various chemical tests of the urine and the blood. 1-Urinary Glucose examination. In general, a normal person loses undetectable amounts of glucose, whereas a person with diabetes loses glucose in small to large amounts, in proportion to the severity of disease and the intake of carbohydrates(it is not s accurate because blood glucose must reach above 180 mg/dl to appear in urin.). 2-Fasting Blood Glucose and Insulin Levels. The fasting blood glucose level in the early morning is normally 80 to 90 mg/100 ml. A fasting blood glucose level above this value often indicates diabetes mellitus or at least marked insulin resistance.

66. In type I diabetes, plasma insulin levels are very low or undetectable during fasting and even after a meal. In type II diabetes, plasma insulin concentration is higher than normal and usually increases after meal. Postbrandial blood sugar test: 2 hours after a meal, we measure the blood sugar, it must return to normal if not DM. Glucose tolerance test: when a normal, fasting person ingests 1 gram of glucose per kilogram of body weight, the blood glucose level rises from about 90 mg/100 ml to 120 to 140 mg/100 ml and falls back to below normal in about 2 hours. In a person with diabetes, the fasting blood glucose concentration is almost always above 110 mg/100 ml and often above 140 mg/100 ml. Also, the glucose tolerance test is almost always abnormal. On ingestion of glucose, these people exhibit a much greater than normal rise in blood glucose level (blood glucose will not return back to normal unless after 4-6 hours), furthermore, it fails to fall below the control level.

67. Insulinoma—Hyperinsulinism: Although much rarer than diabetes, excessive insulin production occasionally occurs from an adenoma of an islet of Langerhans. Sometimes these adenomas are malignant. The central nervous system normally derives essentially all its energy from glucose metabolism(about 60% of glucose is consumed by the brain),so the first organ to be affected when glucose decreased is the brain .However, if high levels of insulin cause blood glucose to fall to low values, the metabolism of the central nervous system becomes depressed. Consequently, in patients with insulin-secreting tumors or in patients with diabetes who administer too much insulin to themselves, the syndrome called insulin shock may occur as follows.

68. As the blood glucose level falls into the range of 50 to 70 mg/100 ml, the central nervous system usually becomes quite excitable, Sometimes various forms of hallucinations result, but often the patient experiences extreme nervousness, sweating. As the blood glucose level falls to 20 to 50 mg/100 ml, seizures and loss of consciousness are likely to occur. As the glucose level falls still lower, come ensues. It is difficult by simple clinical observation to distinguish between diabetic coma as a result of insulin-lack acidosis and coma due to hypoglycemia caused by excess insulin. The acetone breath (acidosis and dehydration) and the rapid, deep breathing of diabetic coma are not present in hypoglycemic coma.

69. 3- Acetone Breath. Small quantities of acetoacetic acid in the blood, which increase greatly in severe diabetes, are converted to acetone. This is volatile and vaporized into the expired air.