Transcript PowerPoint Slides

Endocrine Physiology
and
Disorders
Endocrine Systems

Intercellular communication network

Hormones travel from cell to cell through the
bloodstream

Regulates complex phenomenon:
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Stress Response
Growth and Development
Fluid and Electrolyte Balance
Reproduction
Solubility of Hormones Determines
Mechanism of Action
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Lipid soluble hormones
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
steroid
thyroid
Water soluble hormones
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proteins and peptides
catecholamines
Feedback Regulation
liver
GH
ACTH
adrenal
cortex
anterior
posterior
ADH
kidney
TSH
thyroid
PRL FSH, LH
Oxytocin
breast
uterus
Feedback Regulation
T3, T4
cortisol
somatomedin
osmolality
GH
ACTH
anterior
posterior
ADH
TSH
Oxytocin
PRL FSH, LH
Negative Feedback
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Feedback signals decrease secretion by
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down regulation of receptor number
decreased sensitivity of receptors
– eg. thyroid hormone down regulates TRH
receptors on thyrotroph cells in the
pituitary
Primary vs Secondary Disorders
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Primary Disorders are due to dysfunction of
the target gland.
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Secondary Disorders are due to dysfunction
of the pituitary gland.
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Primary and secondary can be differentiated
by looking at feedback loops.
Endocrine Disorders
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Hyperfunction
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Hypofunction
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Etiology
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Etiology
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autoimmune
stimulation
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autoimmune inhibition
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nonsecreting tumors
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secreting tumors
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surgical removal
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idiopathic
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ischemia, infarct
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receptor defects
Treatment
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surgical removal
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blocking drugs
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irradiation
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Treatment
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hormone therapy
Causes of endocrine disorders
Acromegaly
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GH secreting pituitary adenoma
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headache, visual disturbances
hyperglycemia “diabetogenic”
increased lean body mass
– bone and soft tissue
Treatment
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hypophysectomy
irradiation
Thyroid Hormone Synthesis
Thyroid Hormone
synthesis is done
by the enzyme:
Thyroid Peroxidase
TSH
Y
T3, T4 secretion
thyroglobulin
T3
T4
Iodine
Triiodothyronine and Thyroxine
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About 90% is T4
Most abundant
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About 10% is T3
Most biologically active
Actions of Thyroid Hormones
T3
T4
T3
rT3
plasma
membrane
T3 combines with a nuclear
receptor--------> affects DNA:
increased oxygen use
increased BMR
increased heat production
increased cardiac output
increased ventilation
gluconeogenesis
enhanced SNS actions
Hyperthyroidism
History
Physical
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weight loss
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warm, moist skin
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increased appetite
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thin, fine hair
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nervousness
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increased BP, HR
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heat intolerance
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hyperreflexia
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palpitations
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fine tremor
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increase bowel
motility
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eyelid, retraction, lag
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enlarged thyroid
Etiology of Hyperthyroidism
Primary
Secondary
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Graves Disease
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Pituitary adenoma
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Thyroid tumor
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Exogenous thyroid
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Thyroiditis
Pathophysiology of Graves Dx
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Etiology: Autoimmune
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High association with HLA D3 and B8
Women affected 8 to 1
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Pathogenesis: IgG autoantibodies bind to
and stimulate TSH receptors on thyroid.
Thyroid hyperplasia and hypersecretion
result
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Exophthalmos due to IgG
Treatment
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RAIU ablation
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Symptom control with beta blockers
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PTU and thyroxine to inhibit synthesis
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thyroxine may reduce relapse which often
occurs with PTU alone
Surgery
Thyroiditis
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Initially: Increased thyroid hormone release
leads to hyperthyroidism, but RAIU is low
and synthesis is low
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Next: Hormone depletion leads to a period of
hypothyroidism
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Finally: Most will recover and become
euthyroid in 2-6 months
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RX: b-blockers, NSAID, ASA, steroids
Hypothyroidism
History
Physical
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weight gain
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dry, dull skin
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fatigue
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coarse hair
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amenorrhea
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hoarse voice
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cold intolerance
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low HR, BP
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constipation
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decreased DTR
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periorbital edema
Hypothyroidism
Primary
Secondary
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Hashimoto
thyroiditis
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Iatrogenic (surgery,
RAIU ablation)
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Iodine deficiency
Pituitary failure
Laboratory Evaluation
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T3, T4 may initially be normal or low
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TSH is a better indicator of hypothyroid
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Primary hypothyroid: high TSH
Secondary hypothyroid: low TSH
Replacement of thyroid hormone
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Synthetic T4 (Synthroid)
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average dose is 110 - 120 mcg/day
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Monitor TSH level
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Overtreatment can lead to osteoporosis in
postmenopausal women: If TSH too low,
reduce replacement dose.
Adrenocortical Hormones
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Sugar: glucocorticoids (cortisol)
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Salt: mineralocorticoids (aldosterone)
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Sex: androgens, estrogens
Regulation of Cortisol Secretion
Sleep-wake pattern
light-dark cycle
7-13 Pulses
per day of
CRH from
hypothalamus
ACTH secretion
Cortisol peak at 2:00-4:00 am
Cortisol nadir at 10 pm -midnight
Stress
pain
infection
cortisol level
Actions of Cortisol
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Metabolism: gluconeogenesis, insulin antagonist,
increased appetite, mobilization of fat stores
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Muscle: increased contractility, breakdown of protein
to form glucose
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Bone and Connective: decreased bone and
collagen formation
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Vascular: enhances effect of catecholamines,
reduces vascular permeability, mineralocorticoid
effects
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Immune: inhibits the immune system in a number
of ways
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CNS: alters auditory, olfactory and taste acuity,
mood, sleep
Adrenocortical Hypersecretion
History
Physical
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weight gain
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central obesity
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fatigue
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muscle wasting
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menstrual
irregularity
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striae
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hyperglycemia
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hypertension
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hirsutism
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weakness
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easy bruising
Etiology
Cushing Disease
Cushing Syndrome
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Adrenal adenoma
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Adrenal carcinoma
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Ectopic ACTH
(cancer)
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Exogenous steroids
Pituitary adenoma
Laboratory Evaluation
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24-hr urinary free cortisol (increased)
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Dexamethasone suppression test:
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If suppression of cortisol, then secondary
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Plasma ACTH (low in primary, high in
secondary)
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CRH stimulation test (increases cortisol in
secondary, no effect in primary)
Treatment of Cushing Syndrome
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If on exogenous steroids, try to wean
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If tumor, surgery or irradiation
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If inoperable, drugs to inhibit synthesis
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e.g. Mitotane, and inhibitors of enzymes in
the cortisol pathway
Adrenocortical Insufficiency
History
Physical
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hyperpigmentation
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tachycardia
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hypotension
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hypoglycemia
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hyperkalemia
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ACUTE: N&V,
headache, bleeding
may be
asymptomatic
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weakness
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weight loss
Etiology
Primary
Secondary
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autoimmune
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pituitary failure
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adrenalectomy
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steroid withdrawal
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infarction
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congenital aplasia
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congenital enzyme
deficiency
(Adrenogenital
syndrome)
Laboratory Evaluation
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Plasma cortisol level (low)
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ACTH level (high in primary, low in
secondary)
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ACTH stimulation test (no response in
primary)
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Serum potassium (high if associated
deficiency of aldosterone)
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Serum glucose (low)
Replacement Therapy
ACUTE
CHRONIC
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Hydrocortisone
100mg now, then
continuous infusion
for 24 hr.
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Prednisone,
cortisone and
hydrocortisone are
used
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Fluid replacement
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Convert to oral
meds if stable
Twice daily dosing,
2/3 in am, 1/3 in pm
Regulation of Insulin Secretion
Glut-2
Liver
Releases
glucose
and
ketones
GLUCOSE
glucagon
insulin
somatostatin
Endocrine Pancreas
Increased
secretion
of Insulin
Decreases
blood glucose
Major Actions of Insulin
Action on Cell
glucose uptake
Effect on Blood
blood glucose
glycogen formation
gluconeogenesis
protein synthesis
blood amino acids
fat deposition
blood FFA
lipolysis
blood ketones
K+ uptake
blood K+
Figure: 41-4
Metabolism in type 1 diabetes
What hormones affect blood
glucose level?
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Hormones that
increase glucose:
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growth hormone
catecholamines
glucagon
thyroid
glucocorticoids
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Hormones that
decrease glucose:
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insulin
Somogyi Phenomenon
Hypoglycemia
Insulin
administration
Release of:
growth hormone
catecholamines
glucagon
cortisol
Hyperglycemia
Diabetes Mellitus
Insulin Dependent (Type 1)
Non Insulin Dependent (Type 2)
Compare Type 1 and Type 2
Type 1
Type 2
Onset
any age
adults
Weight
underweight
obese
Immune-mediated
YES
NO
Ketoacidosis
YES
NO
Insulin secretion
NO
YES
Beta cell function
NO
YES
HLA-linkage
YES
NO
Diagnostic Criteria
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Nonpregnant Adults:
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random glucose > 200 mg% plus symptoms
OR: fasting glucose > 126 mg%, twice
OR: fasting glucose < 126 mg%, but OGTT
is > 200 mg% at 2 hours
Impaired Glucose Tolerance:
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fasting glucose < 126 mg%, 2 hr OGTT is
between 126-200, 0-2 hr is > 200 mg%
Pathogenesis of Diabetes
Impaired Transport of Glucose
into Cells
CELL ENERGY
HYPERGLYCEMIA
breakdown of
fat and protein
blood osmolality
cells shrink
glycosuria
ketogenesis
dehydration
Fruity Kussmaul Coma
breath resp
thirst
HR
warm,dry
Compare DKA with HHNS
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DKA
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HHNS
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ketoacidosis
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no ketoacidosis
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mod elevated
glucose
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high glucose >800
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severe dehydration
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coma
Goals of Treatment
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Normalize Blood Glucose
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<180 mg% postprandial, <130 mg% fasting
– Self monitor blood glucose routinely
– Normal blood glucose: 70-115 mg%
– Minimize hypoglycemic events
Keep HbA1c < 7.0% (3.9-6.9%)
– Reflects glucose level over past 2-3
months
– HbA1c increases 1% for each increase of
30mg% in blood glucose
Goals of Treatment
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Avoid Long-term Vascular and Neurological
Complications
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Glycosylated proteins, enzymes contribute to
atherosclerotic processes:
– retinopathy, nephropathy, MI, CVA,
peripheral vascular disease
Neurons don’t require insulin, are exposed to
high intracellular glucose:
– peripheral neuropathy, autonomic
neuropathy
Treatment of Diabetes
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Diet:
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Exercise
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low in simple sugars, fat. Adequate protein
and complex carbohydrates
weight loss for obese Type 2
consistent, regular timing
Drug therapy
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Insulin for both Type 1 and Type 2
oral agents for Type 2 only
ACE Inhibitors
Oral Agents for Diabetes
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Sulfonylureas (hypoglycemics, increase
secretion of insulin from pancreas)
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First generation: Tolinase, Diabinese
Second generation: Diabeta, Glucotrol
Biguanides (decrease tissue resistance, do
not cause hypoglycemia)
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metformin (Glucophage)
Teaching, Teaching, Teaching
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Blood glucose monitoring
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Urine ketone monitoring
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Drug onset, peak
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Short and long term complications to monitor
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When to call the provider, enter the hospital
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Diet and Exercise plan
KNOW THE DIFFERENCE
HIGH
Blood Sugar
Increased thirst
and urination
ketones in urine
aching, weak
heavy breathing
nausea,vomiting
fatigue
cold sweats
headache
trembling
pounding heart
sleepiness
personality
change
hunger
LOW
Blood Sugar
The End…