Download FUNCTION/DYSFUNCTION OF ENDOCRINE PANCREAS

FUNCTION/DYSFUNCTI
ON 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 (opposite function as insulin)
– Beta cells – secrete the hormones
insulin and amylin (similar function as
insulin)
– 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:
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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
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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
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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
Type 1 or IDDM - Insulin Dependent Diabetes
Mellitus
Type 2 or
NIDDM - Non-Insulin Dependent Diabetes
Mellitus
GDM - Gestational Diabetes Mellitus
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Type 1 or IDDM
Accounts for 10% all DM in the Western world ~1015% 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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Imbalance of hormones produced by islets of
Lagerhans : low insulin and high glucagon
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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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Fats and proteins are metabolized
excessively, and byproducts known as
ketone bodies are produced. These are
released to the bloodstream and cause:
Decreased pH (increased acidity), 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 patient’s total calories
Fats should make up <30% of patient’s
total calories
Proteins should make up about 15-20%
of patient’s 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 > 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
decreased β cell responsiveness →
Decreased insulin secreted by β cells
Also abnormal amount of glucagon
secreted
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These effects may be due to:
1.Abnormally functioning β cells
2. Decreased β 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 β cells to increase insulin
secretion
Works only when β cells are still
functioning
→ An enhancement of insulin’s 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 body’s cells
This “antagonizes” the effects of any glucose
present 
Increased ketones in blood
Acid/base imbalance
Polyuria, dehydration
Electrolyte disturbances
Hyperventilation (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
Degeneration of neurons →Sensory,
motor deficits →Muscle atrophy,
paresthesias
G.I. problems, as decreased muscle
motility
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
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
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
diabetic patients face problems with
their lower legs and feet
Increased risk of infections
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