Endocrinology 3 The endocrine pancreas Flashcards
Islets of Langerhans:
- endocrine-involved cells and what they produce
- alpha cells -glucagon
- beta cells –insulin
- delta cells - somatostatin
- F cells -pancreatic polypeptide
pancreas response to low blood glucose
- glucagon released by alpha cells of pancreas
> liver releases glucose into blood
pancreas response to high blood glucose
- insulin released by beta cells of pancreas
> fat cells take in glucose from blood
effects of insulin in skeletal muscle, liver, and adipose tissue
skeletal muscle:
- increase amino acid reflux
- increase protein synthesis
- increase glycogen synthesis
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liver:
- decrease gluconeogenesis
- increase lipgenesis
- increase glycogen synthesis
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Adipose tissue:
- decrease lipolysis
- increase lipogenesis
Diabetes - primary
- Type 1 vs type 2
Type I (Insulin Deficient Diabetes, IDD) = loss of b cells, young to middle age, fairly sudden onset, dependent on insulin treatment (insulin-dependent diabetes mellitus, IDMM)
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Type II (Insulin Resistant Diabetes, IRD) = insulin resistance of tissues and/or “dysfunctional” b cells,
gradual onset, may be non-insulin dependent for a while
Secondary hyperglycemia (diabetes)
- causes
- Carbohydrate intolerance secondary to insulin antagonists (epinephrine, cortisol, glucagon, growth hormone)
- Transient diabetes that may resolve or become sub- clinical
- High progesterone states i.e.diestrus in the dog, or cats treated with megesterol acetate
- Gestational diabetes
Type I diabetes
- what is it in people?
- is it common in dogs?
- age?
- breeds?
- association to other conditions?
- People: genetics + environmental factors > immune- mediated insulitis > impaired insulin secretion > overt diabetes with complete b cell destruction.
- Virtually all canine diabetes is type I, onset middle age
- Genetic predisposition - Keeshonds, Cairn terriers, Min. Pinscher, Min. Schnauzers, dachshunds, small poodles
- Role of pancreatitis in dogs?
Type II diabetes
- how common? in cats?
- pathogenesis
- associations?
- 30-50% of feline DM is non- or variably insulin-dependent
- Likely pathogenesis: muscle and adipose tissue are glucose intolerant due to obesity or concurrence of GH hypersecretion > chronic over-secretion of insulin > co- secretion of islet amyloid polypeptide (IAPP) > transformation to insoluble amyloid > partial or complete destruction of b cells
- Strong association of typeII DM with obesity in cats (and people)
Type II diabetes
Pathophysiology:
Downregulation of insulin receptors, decreased affinity of receptor for insulin, reduced action of intracellular insulin in obesity
= carbohydrate intolerance
Glucose tolerance test in type II diabetes –
- In healthy cats, injection of a bolus of glucose causes a rapid release of insulin from pancreatic islets, which quickly returns the blood glucose concentration to normal limits.
- In cats with subclinical (pre-diabetic) type II diabetes and insulin resistance, injection of a bolus of glucose causes a delayed and greater release of insulin, which corresponds to a longer period of hyperglycemia.
- Cats with insulin resistance usually overproduce insulin for months to years before they are diagnosed as diabetic.
Diabetes
Pathophysiology (type I)
- Insulin deficiency results in decreased tissue utilization of glucose, amino acids, and fatty acids.
- Persistent glucosuria develops once plasma glucose >10-12 mmol/L (dog) and >16 mmol/L (range 11-18) (cat)
- Persistent hyperglycemia
- Osmotic diuresis = PU/PD
- Lack of satiety response from cells in hypothalamus = polyphagia
- Metabolism of protein and fat = weight loss
Diagnosis of diabetes
- signalment
- history
- PE
- Signalment: female dogs and male cats slightly more frequently affected
- History: polydipsia/polyuria, polyphagia, weight loss, sudden blindness (cataracts), ketoacidotic crisis
- Physical exam: Hepatomegaly, neuropathy
Diagnosis of diabetes mellitus
- lab abnormalities
- Hyperglycemia & glucosuria
- Increased liver enzymes
- Increased pancreatic enzymes - pancreatitis
- Azotemia – rare
- Hyperlipidemia - increased lipolysis, decreased lipoprotein lipase activity
- Urinary tract infection - glucosuria, proteinuria, pyuria
Differential diagnosis of hyperglycemia:
- DM (has glucosuria)
- Stress (cat) – epinephrine-induced, may be as high as 22 mmol/L, generally no glucosuria
- HAC – insulin antagonism of glucocorticoids
- Pancreatitis – glucose commonly <15 mmol/L
- Acromegaly – GH secreting pituitary tumor (cats)
- Diestrus, pheochromocytoma, postprandial
Diagnosis of diabetes
- steps we should follow
- Establish diagnosis of DM from general laboratory data.
- Differentiate IDDM from NIDDM: severity of hyperglycemia, presence of ketoacidosis, response to insulin administration
- Specific tests: rarely needed
Diagnosis of diabetes
Intravenous glucose tolerance test (IVGTT, rarely needed):
- 24 hr hospital acclimatization
- IV catheter
- Fast overnight
- Baseline blood sample
- Administer 0.5 g of 50% dextrose/kg body weight iv over 30 sec
- Blood samples for glucose and insulin determination at 1, 5, 10, 20, 30, 45, 60, 90 and 120 min.
Glucose/insulin curve
- Concurrent glucose and insulin measurements over 24 hours to assess the response to insulin
- Measurement of insulin by RIA > needs to be validated for species
- Human and dog insulin almost identical, therefore human kits work well in dogs
- Cat insulin different from dog and human, only a few kits designed for humans work with cat samples
Glycated proteins
1. Glycosylated hemoglobin (gHb, HbA1c):
- what it tells us
- insulin-independent binding of glucose to hemoglobin in red blood cells
- expressed as % of total hemoglobin
- consider hematocrit and red cell lifespan for interpretation
- not readily available for animals but mainstay of long-term monitoring in people
<><><><> - RBC life span: 60-70 days in the cat, ~120 days in the dog
- Therefore: amount of gHb indicates glycemic control over 2-4 months
Glycated proteins
2. Fructosamine
- what is this?
- what can we learn from blood levels?
- things that can interfere
- Generic name for glycated serum proteins (ketoamines)
- Mainly albumin; not all serum proteins are susceptible to glycation
- Reflects glycemic control over 2-4 week period (T1/2 of albumin)
- Automated colorimetric assay
- Interference with severe hypoalbuminemia and hypertriglyceridemia
> Glycated protein concentration is not influenced by transient hyperglycemia.
Diabetic ketoacidosis
- pathogenesis
insufficient of absent insulin
- cells are starving for glucose > breakdown of protein, fat, and glycogen
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> increased glucagon
> fat cells mobilized: glycerol, fatty acids
> muscle cells break down into amino acid constituents
> all of this stuff plus other substrates moves to the liver
> glycogenolysis, gluconeogenesis, ketogenesis
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- increased ketone and glucose production
> increased ketone and glucose in bloodstream
> Osmotic diuresis, acidosis ketonuria, glucosuria
> dehydration
> Hypovolemia, acidosis, shock
“Ketone bodies”
- what are they?
- tests?
- acetoacetate > acetone, beta-hydroxybutyrate
<><><><> - Ketone bodies are produced by the liver from fatty acids and some amino
acids, and used as an energy source when glucose is not available (diabetes). - Most ketone tests detect mainly acetoacetate, to a lesser degree acetone, and no b-hydroxybutyrate, although the latter is the main product during ketosis.
Diabetic ketoacidosis (DKA)
- pathophysiology
- Hyperglycemia and glucosuria > osmotic diuresis and concomitant electrolyte loss
- Accumulation of ketone bodies > metabolic acidosis
- Nausea and/or vomiting > exacerbation of ketone production and acidosis
- Increase in plasma osmolality > cellular dehydration > cerebral edema
- H+-K+ shift leading to whole body hypokalemia
Pancreatic endocrine neoplasms
- Insulinoma
- Gastrinoma
- Glucagonoma
Insulinoma
- what is this?
- how bad? effects?
- diagnosis?
- Tumor of pancreatic b cells
- Insulin production
- Malignant tumors – metastasis common at the time of diagnosis
- Release of insulin despite hypoglycemia > weakness, seizures
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Diagnosis: fasting hypoglycemia (<3.3 mmol/L) with normal or high insulin concentration
Differential diagnosis for hypoglycemia:
- hepatic portosystemic shunt
- severe liver disease
- hypoadrenocorticism
- tumors producing hypoglycemic substance (hepatic or intestinal tumors)
- sepsis
Insulinomas in ferrets
- common?
- same presentation as what other condition
- can it be cured?
- The most common tumor in ferrets!
- Same clinical presentation due to hypoglycemia
- But not as malignant as in dogs … surgery is often curative
Gastrinoma
- what is this?
- effects?
- clinical signs
- dx
- prognosis
- Gastrin in adult life is produced by
gastric and intestinal epithelial cells - Gastrin causes excessive gastric acid secretion
- Animals and persons with overproduction of gastrin have Zollinger-Ellison syndrome: vomiting, diarrhea, GI ulceration and pancreatic mass
- Diagnosis: basal gastrin concentration (reliable) and gastrin stimulation tests
- Prognosis: poor, metastasis common
Glucagonoma
- what is it
- species
- what happens
- clinical signs
- Tumor of pancreatic α cells
- Dogs only
- Superficial necrolytic dermatitis due to low blood amino acid concentration
- Increased glucagon > gluconeogenesis, glycogenolysis, ketogenesis
- Mild DM, venous thrombosis, glossitis/stomatitis, diarrhea
- Metastasis?
parathyroid gland - what does it do?
secretes parathyroid hormone (in response to low serum Ca)
- acts on kidney: 25-hydroxyvitamin D > 1,25-dihydroxyvitamin D > increased calcium absorption in the GI tract
- acts on bone > increased bone resorption
> overall, acts to increase serum Ca > negative feedback to secrete less PTH
Hyperparathyroidism effects on kidney and bone, overall
Kidney:
- increased re-absorption of Ca
- decreased re-absorption of P
- increased production of active
cholecalciferol
> Intestine: increased Ca and P absorption
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Bone:
- increased osteoclast activity, bone resorption > increased Ca and P
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- Hypercalcemia = BAD!
> Kidney disease, soft tissue mineralization, GI abnormalities, ‘feeling bad’
Calcitonin:
- where does it come from, what does it do?
- Produced by parafollicular C cells in the thyroid gland in response to hypercalcemia.
- Decreases bone re-sorption – limited effect
- No effect on kidney or intestine.
Hyperparathyroidism
- usual causes
- presentation, signs
- Most commonly due to autonomously secreting adenoma of “chief” cells in parathyroid glands
- Adenomas are rarely palpable in dogs
- If palpable > consider carcinoma
- Adenomas palpable in 50% of cats
- Keeshond more commonly affected?
- Presenting signs: non-specific, PU/PD, weakness
Hyperparathyroidism dx
Diagnosis (fairly straightforward)
1. Marked and persistent hypercalcemia
2. Low or low-normal serum P concentration
3. Increased serum PTH “2-site” (intact) assay
Hypercalcemia
Differential diagnosis:
- Hypercalcemia of malignancy
- marked hypercalcemia and low to normal P concentration, low PTH concentration - Chronic renal failure
- variable serum Ca, normal or high P, low to normal Ca++, high PTH - Hypervitaminosis D (cholecalciferol toxicosis)
- hypercalcemia and hyperphospatemia - Hypoadrenocorticism, nutritional 20 hyperparathyroidism, systemic mycotic disease
Hyperparathyroidism in cats
- signs
- Mass often palpable
- PU/PD uncommon
- Consistent marked hypercalcemia and hyperparathyroidemia, variable hypophosphatemia
hyperparathyroidism in reptiles
Diet high in P and low in Ca > secondary hyperparathyroidism > removal of Ca from bones > fibrous dystrophy and pathologic fractures
Hypoparathyroidism
- common?
- cause?
- age, sex…
- history
- Uncommon disease
- Cause? Likely autoimmune mechanism of destruction
- Young to old animals affected, no sex predilection in dogs, but males more commonly in cats
- History: abrupt neuromuscular abnormalities (seizures, tetany, facial rubbing, muscle fasciculations)
Hypoparathyroidism Dx
Diagnosis:
* Persistent severe hypocalcemia and hyperphosphatemia in the absence of azotemia
* Undetectable serum PTH concentration with hypocalcemia
Differential diagnosis for hypocalcemia:
- Iatrogenic following thyroidectomy
- Chronic renal failure (clinically silent)
- Hypoalbuminemia
- Acute pancreatitis
- Ethylene glycol toxicity
