Exam 8: L. 8: Glucose! Flashcards
Normal blood glucose
1) sole source of energy for the brain (to a limited extent in extreme cases the brain may use ketone bodies)
- blood glucose kept tightly regulated
- normal blood glucose: 70-120 mg/dl
Glycogenolysis
Hepatic glycogen stores exhausted after 2-3 days of fasting
-glycogen stores depleted = = >gluconeogenesis
Where does gluconeogenesis occur?
1) liver*
2) kidney
Insulin
1) promote cellular uptake of:
- glucose*
- also amino acids, fatty acids, and electrolytes
2) promote storage of glucose as glycogen
3) inhibits lipolysis and subsequent release of FFA into circulation
4) inhibits gluconeogenesis and glycogenolysis
Normal response to hypoglycemia
1) blood glucose falls below 70 mg/dl:
- stimulates release of hormones: cortisol, catecholamines, growth hormone, glucagon (DIABETOGENIC HORMONES)
Normal response to hypoglycemia
1) net effect of the diabetogenic hormones:-promotes gluconeogenesis
- promotes glycogenolysis
- decreased peripheral glucose use
- shutdown insulin secretion
RESULT: normalize blood glucose
Etiologies of hypoglycemia
1) lack of intestinal absorption
- severe malnutrition/starvation
- severe intestinal disease
2) lack of hepatic production
- portosystemic shunts*
- hepatic failure*(acute or chronic)
- glycogen storage diseases (usually genetic disorders)
3) endocrine disorders
- lack of diabetogenic hormones (Addison’s disease)
4) increased glucose utilization
- sepsis!
- Polycythemia (excess red blood cells use of glucose)
- extreme exertion
- too much insulin (insulinoma)
More etiologies of hypoglycemia
1) xylitol toxicity
- induces insulin release!!
2) paraneoplastic
3) artifact-if blood sits out longer than it should it may appear falsely hypoglycemic
Clinical effects of hypoglycemia
1) CNS carbohydrate reserves are limited-dependent on a continuous supply from outside CNS
2) cerebral cortex is the 1st area affected by hypoglycemia
3) glucose entrance into CNS is NOT insulin-dependent
Neurologic sequela
1) brain is 1st organ affected by hypoglycemia
2) clinical signs result from:
- Neuroglycopenia (lack of glucose to brain)
- sympathoadrenal stimulation (diabetogenic hormones: epinephrine-anxiety, tremors)
Clinical signs: neuroglycopenia
1) weakness
2) lethargy
3) ataxia
4) behavioral change
5) seizures
6) coma
Clinical signs: sympathoadrenal
1) muscle tremors
2) nervousness
3) restlessness
4) hunger
Clinical signs of hypoglycemia
1) depend on duration and severity of hypoglycemia
2) rapid*onset of hypoglycemia = more severe signs
- i.e.: insulin overdose, sepsis
3) chronic onset = animal may be relatively asymptomatic with significant hypoglycemia
- i.e.: insulinoma
Clinical approach
1) consider list of differentials and decide which is most likely
2) hypoglycemia mild (>45 mg/dl) -Addison’s disease, hepatic disease
3) hypoglycemia severe (<40 mg/dl)-sepsis, neoplasia, juvenile
Insulinoma
1) tumor of pancreatic beta cells
- autonomously secretes insulin = hypoglycemia
- majority are malignant and have gross/microscopic metastasis at time of diagnosis
2) common in ferrets, uncommon in dogs (large breeds overrepresented, 9-10 years), rare in cats
Insulinoma
1) Chronic, insidious onset
- may have severe hypoglycemia with relatively mild clinical signs
2) demonstrate (inappropriately) high insulin with concurrent low*glucose
- MUST measure insulin when blood glucose is low (ideally <50 mg/dl)
Emergency therapy for hypoglycemia
1) IV catheter
2) 50% dextrose
3) administer 1-5 ml/kg slowly over 10 minutes
4) hyperosmolar, therefore dilute 1:4
5) total infusion amount 4-20 ml solution
* treat to resolution of clinical signs
Use caution…
1) insulinoma may respond poorly to dextrose administration
- increase in blood glucose promotes insulin secretion
- ultimate worsening of hypoglycemia!
2) treat the ANIMAL not the BG
- alternative option: glucagon (if patient doesn’t respond well to glucose)
Hyperglycemia
Normal finding postprandial
- 2-4 hours after eating (mild)
2) hyperglycemia etiologies: - too much of one or more hormones that raise BG
- deficient in hormone that decreases BG (insulin-diabetes)
- various drugs
Too much hormone
1) hypoglycemia not sold clinical presentation
2) successful treatment of underlying etiology should lead to resolution of hyperglycemia
3) therapy for hyperglycemia (insulin) usually*only indicated for acromegaly (potentially it may cause diabetes)
Stress hyperglycemia
1) sources
-catecholamine release
glucocorticoids (endogenous or exogenous)
2) blood glucose can exceed renal threshold in stress
-hyperglycemia and glucosuria
-dogs (180 mg/dl), (280 mg/dl)
Not enough hormone to decrease glucose
1) insulin: beta cells of endocrine pancreas
2) insulin deficiency = diabetes mellitus
- anything destroying beta cells of pancreas or interfering with insulin action = diabetes
DM pathophysiology-step 1
Insulin deficiency (relative or absolute)
1) decreased tissue utilization
2) increased hepatic glycogenolysis and gluconeogenesis
3) glucose from liver and diet accumulates in circulation
4) results inhyperglycemia
DM pathophysiology-step 2
Hyperglycemia
1) exceeds renal tubular resorption abilities
2) eventualglucosuria
3) causes and osmotic diuresis
4) results inpolyuria
5) results in compensatorypolydipsiato prevent dehydration
DM pathophysiology-step 3
1) satiety center in the brain normally inhibits the feeding center after a meal
2) satiety center requires insulin for glucose transport
3) insulin deficiency = glucose does not enter satiety center = failure to inhibit feeding center
4) results inpolyphagiain face of hyperglycemia
Classic signs of diabetes mellitus
1) polyuria
2) polydipsia
3) polyphagia
4) weight loss (cells aren’t taking up energy!)
Diabetes mellitus
1) most common endocrine disease in dogs and cats
2) hyperthyroidism probably most common endocrine disease of older cats (>8 years)
3) many similarities and many differences between dogs and cats with DM
DM signalment’s
Dog = 7-10 years, females >males
= most >6 years, neutered males
Types of DM
1) Type 1 = “insulin-dependent”
- most common type in DOGS-absolute and permanent insulin deficiency
- genetic predispositions, support for auto-immune component
2) Type 2 = “non-insulin-dependent”
- most common type in CATS
- relative/possible reversible insulin deficiency
- defective pancreatic beta cells
- one or more sources of insulin resistant
BOTH are treated with insulin
Diagnosis of DM
Resting hyperglycemia with glucosuria in animals with clinical signs (the 3 P’s with weight loss!!)
