FUNCTION/DYSFUNCTION OF ENDOCRINE PANCREAS

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FUNCTION/DYSFUNCTION OF ENDOCRINE PANCREAS

• Diabetes

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Anatomy of the pancreas Both an exocrine and
endocrine organ Cells with exocrine function
release an alkaline fluid containing sodium
bicarbonate and enzymes ? pancreatic duct ?
small intestine Pancreatic juice aids in
breakdown and digestion of food in the small
intestine Pancreatic exocrine cells acinar cells
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Endocrine Function Cells of the Islet of
Langerhans synthesize and release hormones into
the circulation. Hormones travel through the
bloodstream to target tissues (especially liver
and muscle) At the target cells, hormones bind
specific receptors and cause cell changes that
control metabolism
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• Pancreatic endocrine cells regulate carbohydrate,
  fat, protein metabolism
• Alpha cells secrete the hormone glucagon
• Beta cells secrete the hormones insulin and
  amylin
• Delta cells secrete the hormones gastrin and
  somatostatin
• F cells - secrete hormone pancreatic polypeptide

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Beta Cells
Synthesize pre-proinsulin, a protein This is
cleaved by enzymes ?proinsulin, then cleaved
again ? insulin Insulin is the biologically
active hormone that is released into the
bloodstream
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Insulin secretion is controlled through several
mechanisms

• Chemically high levels of glucose and amino
  acids in the blood
• Hormonally beta cells are sensitive to several
  hormones that may inhibit or cause insulin
  secretion
• Neurally stimulation of the parasympathetic
  nervous system causes insulin to be secreted.

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Insulin secretion is decreased by

• Decreased blood glucose concentration
• Increased blood insulin concentration
• Sympathetic stimulation

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Insulin

• Transported through the blood to target tissues
  where it binds to specific receptors
• The binding of insulin to target cells
• Acts as a biochemical signal to the inside of the
  cell
• Overall, cell metabolism is stimulated
• There is increased glucose uptake into the cell
• Regulation of glucose breakdown within the cell
• Regulation of protein and lipid breakdown within
  the cell

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• Blood glucose is decreased because insulin causes
  glucose to leave the bloodstream and enter the
  metabolizing cells.
• With the exception of brain, liver and
  erythrocytes, tissues require membrane glucose
  carriers.

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Disorder - Diabetes mellitus

• The single most common endocrine disorder group
  of glucose intolerance disorders
• Incidence is estimated at 1-2 of the North
  American population
• Many of these cases are undiagnosed

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Diabetes mellitus
Historically - distinguished by weight loss,
excessive urination, thirst, hunger Excessive
urination polyuria Excessive thirst
polydipsia Excessive hunger
polyphagia Modern characterization is by
hyperglycemia and other metabolic disorders
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Modern classifications (Table17.7) Type 1 or IDDM
- Insulin Dependent Diabetes Mellitus Type 2 or
NIDDM - Non-Insulin Dependent Diabetes
Mellitus Other Types of Diabetes Mellitus GDM -
Gestational Diabetes Mellitus
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Type 1 or IDDM
Accounts for 10 all DM in the Western
world 10-15 have parent or sibling with the
disease Peak age of diagnosis 12
years Genetic/environmental/autoimmune factors
destroy beta cells Believed abrupt onset now
immunomarkers and preclinical symptoms have been
discovered
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Disequilibrium of hormones produced by islets of
Lagerhans low insulin and high glucagon Ratio
insulin/glucagons apparently controls metabolism
of glucose and fats.
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Clinical Manifestations

• Glucose in urine- Because when insulin is not
  present, glucose is not taken up out of the blood
  at the target cells.
• So blood glucose is very highly increased ?
  increased glucose filtered and excreted in the
  urine (exceeds transport maximum)

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Clinical Manifestations

• Weight loss - Patient eats, but nutrients are not
  taken up by the cells and/or are not metabolized
  properly
• Osmotic diuresis results in fluid loss
• Loss of body tissue by metabolism of fats and
  proteins

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Polyuria, polydipsia, pholyphagia Ketoacidosis Fat
s and proteins are metabolized excessively, and
byproducts known as ketone bodies are produced.
These are released to the bloodstream and
cause Decreased pH (so increased
acidity) Compensations for metabolic
acidosis Acetone given off in breath
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Treatment
1. Administer insulin May be of animal or human
origin Cannot be given orally Patient must
monitor their blood glucose concentration and
administer insulin with the correct timing
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2. Control diet Carbohydrates should make up
about 55-60 of patients total calories Fats
should make up lt30 of patients total
calories Proteins should make up about 15-20 of
patients total calories
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3. Monitor exercise Remember muscles are a
target tissue of insulin, and metabolize much
glucose for energy Sometimes exercise ?irregular
blood glucose levels So diabetic patients should
be monitored when they are exercising
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Other Pancreatic transplant so far not
successful Experimental therapies not as
successful as hoped
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Type 2 or NIDDM
More common than IDDM, often undiagnosed It has a
slow onset Most common in those gt 40 years,
though children are being diagnosed more
regularly May be genetic Obesity is the
greatest risk factor for this disease And is
related to increased incidence in children
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NIDDM ? insulin resistance in target cells See
decreased ß cell responsiveness ? Decreased
insulin secreted by ß cells Also abnormal amount
of glucagon secreted
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• These effects may be due to
• Abnormally functioning ß cells
• Decreased ß cell mass,
• or a combination of the two
• 3. Target cell resistance to insulin
• Due to
• Decreased number of insulin receptors
• Postreceptor events may be responsible
• Cells burn out and become insensitive

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Clinical manifestations
Overweight, hyperlipidemia common (but these are
precursors, not symptoms) Recurrent
infections Visual changes, paresthesias, fatigue
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Treatment
1. Weight loss 2. Appropriate diet (see IDDM
above) 3. Sulfonyl ureas stimulate ß cells to
increase insulin secretion Works only when ß
cells are still functioning ? An enhancement of
insulins effect at target cells 4. Exercise -
promotes weight loss
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Gestational Diabetes
Due to increased hormone secretion during
pregnancy Seen if patient has
predisposition If previous or potential glucose
intolerance has been noted Important - increased
mortality risk for mother, child
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Complications of Diabetes Mellitus
Acute Hypoglycemia rapid decrease in plasma
glucose insulin shock Neurogenic responses
probably due to decreased glucose to
hypothalamus. Symptoms include Tachycardia,
palpitations, tremor, pallor Headache,
dizziness, confusion Visual changes
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Treatment provide glucose (I.V. or
subcutaneous if unconscious) Observe for
relapse
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Ketoacidosis involves a precipitating
event Increased hormones released w/ trauma ?
increased glucose produced by the bodys
cells This antagonizes the effects of any
glucose present ? Increased ketones in
blood Acid/base imbalance Polyuria,
dehydration Electrolyte disturbances Hyperventil
ation (Kussmaul deep, gasping) CNS
effects Acetone on breath
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Treatment - low dose insulin Also,
administer fluids, electrolytes
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Chronic Complications of DM Neuropathies nerve
dysfunctions ? slowing of nerve conduction. In
these patients, see Degeneration of neurons
?Sensory, motor deficits ?Muscle atrophy,
paresthesias Depression G.I. problems, as
muscle motility decreased Sexual dysfunction
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Microvascular disease chronic diabetes w/
improper glucose metabolism ? thickening of the
basement membrane of capillaries, particularly in
the eye and the kidney. As the capillary changes
in this way, ? Decreased tissue perfusion So
ischemia ? hypoxia
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In the eye the retina is metabolically quite
active, so hypoxia here is a big problem So
see Retinal ischemia? Formation of
microaneurisms, hemorrhage, tissue infarct,
formation of new vessels, retinal detachment
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In the kidney diabetes is the most common cause
of end-stage renal disease Injured glomeruli
(glomerulosclerosis) In these patients,
see Proteinuria (protein is excreted into the
urine) ? Generalized body edema, hypertension
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Macrovascular disease atherosclerosis Plaque
formation increases? Increased risk of coronary
artery disease, so increased risk of myocardial
infarction Increased risk of congestive heart
failure Stroke Peripheral vascular disease why
diabetic patients face problems with their lower
legs and feet Increased risk of infections