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							Unit I: Normal Physiology and Pathophysiology
Normal Physiology
Overall, insulin functions as an anabolic agent because it builds the body up as opposed to breaking it
down (catabolic). It is essential for the metabolism of glucose for energy by the cells.

The normal stimulus for the release of insulin from the pancreas into the blood stream is an increase in
the blood glucose. Glucose is the body's preferred fuel. Insulin is later "shut off" and glucagon, a
hyperglycemic agent (as well as a hormone), is secreted by the alpha cells of the pancreas when the
blood glucose drops to a critical level. Glucagon facilitates the conversion of glycogen to glucose in the
liver (gluconeogenesis). Blood glucose levels are maintained within a normal range (homeostasis) in this
way. Diagram 1 illustrates the normal relationship between blood glucose and insulin:




When one eats, the initial result is an increase in blood glucose. Simultaneously, the body responds by
increasing insulin secretion. If the blood glucose becomes too low, glucagon is secreted from the alpha
cells of the pancreas to raise the blood glucose. Simplistically speaking, this is the body's way of
maintaining homeostasis of the blood glucose. There is a normal, predictable rise and fall of the blood
glucose after a meal.

Other hormones in the body influence blood glucose. They are adrenocorticotropic hormone (ACTH) and
epinephrine which are produced in response to stress, and which indirectly elevate the blood glucose.
Consequently, emotional stress can result in elevated blood glucose levels. Chronic stress has been
shown to be related to poor glucose control and thereby an increased incidence of complications.

In the person with normal glucose metabolism, fasting blood glucose (FBG) levels are maintained within a
fairly narrow range of 65-110 mg/dl. Blood glucose levels typically rise with the ingestion of food, but are
normally between 65 and 139 mg/dl at the two-hour post meal point (i.e. the "two-hour post-prandial"
blood glucose level).




Pathophysiology
Diabetes mellitus is a condition resulting from a relative or absolute lack of insulin activity in the body. It is
not simply always "too little insulin," and it is certainly not because the individual "ate too much candy" (a
common misconception).

The graphs below show the typical glucose response to ingestion of food in the non-diabetic and the
person with uncontrolled/undiagnosed diabetes mellitus. (Caution: The blood glucose values shown are
not to be taken literally, but are used to reflect trends. Keep in mind the normal values of blood glucose in
the fasting and post-prandial states as you review the graphs). With insufficient insulin activity (DMT2) or,
in the case of DMT1, an absolute lack of insulin, the blood glucose (BG) remains at excessively high
levels. The kidneys attempt to excrete the excess glucose in the urine leading to profound loss of fluid
and insatiable thirst. Because the body cells cannot make use of the blood glucose due to insufficient (or
absent) insulin, the metabolic processes effectively recognize a state of starvation and resort to the
breakdown of fat and protein, and the hepatic production of glucose to meet energy needs.
Uncontrolled/Undiagnosed Diabetes
Uncontrolled/undiagnosed diabetes is a life-threatening problem. Until 1921, when insulin was discovered
by Dr. Frederick Banting and Charles Best (a medical student who was working with Dr. Banting), the
diagnosis of diabetes (now identified as DMT1) meant certain death. Death came slowly, essentially from
metabolic acidosis and starvation, despite the presence of adequate food. The body simply broke itself
down in an attempt to meet its energy needs. (See Best, 1964 for the exciting story of the discovery of
insulin told first-hand by one of the discoverers!)

At the time insulin was discovered in 1921, the only kind of diabetes that was known was Type 1 – an
absolute lack of insulin. The chemical changes that result from an absolute lack of insulin activity lead to
the four cardinal signs (objective indications) of uncontrolled/undiagnosed DMT1:
Anatomy - Pancreas is an organ situated in the upper part of one’s abdomen. It is
about 6 inches or 15 cms long and has a flattened bulbous head that is surrounded by
part of the intestine called duodenum, a narrow body that lies behind the stomach and
a tapered tail that rests on the front of the left kidney (see picture).


Physiology or Function- Pancreas is one of the organs in the body that has both
exocrine                         and                           endocrinal                         functions.


Exocrine Function - It secretes an alkaline juice with enzymes such as - amylase and
lipase, which help digest the fat, protein as well as carbohydrates from the food that we
eat. The alkaline juice and helps to neutralize the acid secretions of the stomach. It
secretes        about         1.5        liters         of     these        juices       in       a          day.


The enzymes are conveyed to the upper part of the small intestine called duodenum via
a               tube                called                   the             pancreatic                  duct.


Endocrine Function - It also secretes two important hormones namely - Insulin and
Glucagon        which     are    essential        for    regulation    of    glucose      in    the     blood.


During an attack of pancreatitis, the juices are activated within the pancreatic gland and
it begin to digest the pancreas itself causing inflammation, injury and necrosis resulting
in an acutely inflammatory process that results in pancreatitis – so called pancreatic
auto digestion. Where pancreas succumbs to its own digestiveproperties.




The pancreas lies in the epigastrium and left hypochondrium areas of the abdomen

It is composed of the following parts:


   The head lies within the concavity of the duodenum.
   The uncinate process emerges from the lower part of head, and lies deep to superior mesenteric
    vessels.
   The neck is the constricted part between the head and the body.
   The body lies behind the stomach.
   The tail is the left end of the pancreas. It lies in contact with the spleen and runs in thelienorenal
    ligament.
The superior pancreaticoduodenal artery from gastroduodenal artery and the inferior
pancreaticoduodenal artery from superior mesenteric artery run in the groove between the pancreas and
duodenum and supply the head of pancreas. The pancreatic branches ofsplenic artery also supply the
neck, body and tail of the pancreas. The largest of those branches is called the arteria pancreatica
magna; its occlusion, although rare, is fatal.

The body and neck of the pancreas drain into splenic vein; the head drains into thesuperior
mesenteric and portal veins.

Lymph is drained via the splenic, celiac and superior mesenteric lymph nodes.




Topic Review on "The Endocrine System":
Endocrine glands: Endocrine organs, called glands, secrete hormones into the bloodstream. Hormones
affect the activity of target sites that are often located far from the site of release. Exocrine organs direct
the function of their target sites by releasing their active.

Human endocrine system: The major endocrine organs include the hypothalamus and the hypophysis,
or pituitary gland. Other endocrine glands within the body include: thyroid, parathyroids, adrenals,
pancreas, ovaries, and testes.

      The hypothalamus: The hypothalamus is located in the forebrain, directly above the pituitary
        gland. The hypothalamus receives input from other parts of the brain and from peripheral nerves.
        This input affects neurosecretory cells within the hypothalamus.
      The pituitary gland: The anterior pituitary synthesizes its own hormones. Capillaries within the
        anterior pituitary receive signals from the hypothalamus that tell the anterior pituitary whether or
        not to release certain hormones.
      The thyroid gland: The thyroid gland is a bilobed structure found at the trachea. It synthesizes
        and secretes three hormones:
             1. thyroxine (T4),
             2. triiodothyronine (T3), and
             3. calcitonin.

         The parathyroids are four small glands embedded in the thyroid. They produce and secrete
         parathyroid hormone (PTH).

      The adrenal gland: The adrenal glands are located on top of the kidneys. Each gland is
        subdivided into an outer adrenal cortex and an inner adrenal medulla.
      The pancreas: The pancreas is both an endocrine organ and an exocrine organ. The exocrine
        portion of the pancreas secretes digestive enzymes into the pancreatic duct. The endocrine
        portion of the pancreas secretes hormones, including insulin and glucagon.
      The testes: The testes are responsible for the synthesis and secretion of androgens, such as
        testosterone. Interstitial cells, located between the seminiferous tubules of the testes, produce
        androgens.
      The ovaries: The ovaries produce and secrete steroid hormones known as estrogens and
        progesterone.
Pathogenesis

The reason for increased incidence of this disorder involves the interaction of several pathogenic
factors:

           NEUROPATHY.

              ABNORMALFOOT BIOMECHANICS.

              PERIPHERAL ARTERIAL DISEASE.
   POOR WOUND HEALING.