In the hypothalamic pituatary thyroid axis, what is secreted by each?
Hypothalamus - TRH
Ant. Pituatary - TSH
Thyroid - T3, T4
Thyroid hormone has negative feedback on what?
both TRH and TSH release
What is thyroid hormones backbone?
2 tyrosine molecules with ether linkage (MIT: 1 iodine, DIT: 2 iodines)
What linkages form T3?
DIT + MIT
What molecule is formed by DIT + MIT?
rT3
What linkages form T4?
DIT + DIT
What is the main thyroid hormone secreted by thyroid gland?
T4 (thyroxine)
What enzyme catalyzes T4 into T3?
Iodothuronine 5’ deiodinase
How do the three types of Iodothronine 5’ deiodinase differ? (action and location)
type 1 - serum in liver and kidneys
type 2 - intracellular (pituatary, brain, fat)
type 3 - converts T4 to rT3
What is the half life of T3 and T4 in humans and dogs?
human T3 - 1 day
dog T3- 5-6 hours
human T4- 6 days
dog T4 - 8-16 hours
Why do thyroid hormones in humans have longer half life?
more thyroid hormone bound to proteins, less degradation
What percent of T3 is from T4?
80%
Which thyroid hormone has greatest activity? by how much?
T3 has 4x activity of T4
What is the role of rT3?
no activity
What are the 3 proteins that bind to thyroid hormones?
Thyroxine binding pre-albumin
Albumin
TGB
What protein do humans have 3 times as much of compared to dogs?
TGB (thyroxine binding globulin)
What are the % thyroid hormones protein bound in humans and dogs?
Human T3: 99.8%
Human T4: 99.98%
Dog T3: 99%
Dog T4: 99%
What is cretinism?
thyroid deficiency - retarded dwarf
What are the calorgenic effects of thyroid hormone?
increased metabolism, increased body temp
Why does a hypothyroid dog have high serum cholesterol?
decreased lipolysis(?) and bile secretion
How would low thyroid levels affect the skin?
follicle atrophy, bilateral alopecia, myxedema, tragic face
How does low thyroid cause facial nerve paralysis?
decreased conduction velocity in CNS
What are GI signs of hypothyroidism?
decreased motility
What are the repro effects of hypothyroidism?
male - testicular atrophy
female - irregular cycles, abortion
What causes primary hypothyroidism? How many % of cases?
Lymphocytic thyroiditis (95%)
What causes secondary hypothyroidism? How many % of cases?
destruction of thyrotrophs in pituatary by tumor (5%)
Which replacement thyroid hormone is used in dogs?
T3 (L-thyroxine)
Serum T4 levels should be checked how often in patients on Thyroxine?
1-2x per year
What is the most common cause of hyperthyroidism in cats?
thyroid adenoma
How does methimazole decrease thyroid synthesis?
inhibits peroxidase (iodination and coupling of thyroglobulin)
Why would it be a good idea to reversibly treat hyperthyroidism initially? (using methimazole)
in case kidneys cant handle decreased BP
What does the blood work of a hypothyroid dog look like?
normocytic, normochromic, non regen anemia, hypercholesteremia
What are the discharge instructions for cats treated with radioiodine?
special handling of feces and urine
keep away from pregnant women and children
What are some concerns with surgical thyroidectomy?
parathyroid gland
What kind of drug can alleviate some of the symptoms of hyperthyroidism?
beta blockers
What do alpha, beta, and delta cells secrete? effect on glucose levels?
alpha: glucagon - increase
beta: insulin and amylin –>decrease
delta: somatostatin
What glucose transporters is in all mammalian tissue?
GLUT 1and GLUT 3
What glucose transporter is in the liver and pancreas B cells?
GLUT 2
What glucose transporter is located in muscle and fat cells?
GLUT 4
What glucose transpporter is in small intestines?
GLUT 5
What happens to beta cells when they are stimulated?
depolarized
What are the 4 stimulators of insulin secretion?
glucose, AA, fatty acids, GI hormones
What are the 2 inhibitors of insulin secretion?
somatostatin
alpha 2 agonists
What causes the central form of diabetes insipidus?
decreased ADH from posterior pituatary
What causes the nephrogenic form of diabetes insipidus?
cells in kidney cant respond to ADH
What defines type 1 diabetes?
insulin dependent, doesnt produce insulin
What defines type 2 diabetes?
insulin resistance - cats
What are the steps in ketoacidosis?
insulin deficiency –>metabolism of triglycerides/muscle –>FFA –>ketones
What are normal blood glucose levels?
80-120 mg/dl
What are 2 consequences of chronic hyperglycemia?
glycated proteins – nerve and bv damage
neural and ocular damage (sorbitol)
What is the diet recommended for dogs with diabetes? cats?
dog - high fiber, complex carbs
cat - high protein, low carbs
Which insulin type can be given to cats to put them in remission from diabetes?
Glargine insulin
What is insulins effect on carb metabolism?
increase glucose uptake/glycogen synthesis
increased glycolysis
decreased gluconeogenesis
How does insulin effect fat metabolism?
increased storage, increased lipogenesis, decreased lipolysis
How does insulin effect protein metabolism?
increased AA uptake, synthesis and decreased degradation
What receptor is associated with glucose uptake in fat cells?
tyrosine kinase receptor
How does insulin affect potassium in the body?
activated Na/K ATPase, increased K intracellularly
What insulin is most similar to dog insulin?
hog
What insulin is most similar to cat insulin? How much do they differ?
Bovine - differ by 1 AA in A chain
Cattle, sheep, horses, and dog insulin differ in how many AA?
3 AA in A chain
How many units of insulin per mL are held in a U-40 syringe? U-100 syringe?
U-40 = 40 units/mL U-100 = 100 units/mL
Why is insulin crystalized?
zinc helps crystallization???
What insulin has a double peak in dogs? What hours does it happen?
porcine insulin zinc suspension - 4 and 11 hours
What are the 2 long acting insulins?
protamine zinc insulin
Glargine/Lantus
What are the 2 intermediate acting insulins?
isophane insulin(NPH insulin) porcine insulin zinc suspension
In what 3 ways can effectiveness of DM management be assesed?
Glycosylated hemoglobin - not really used
Fructosamines - shows past 2-4 weeks
Glucose curve
What is it called when dose of insulin that is too high (rebound hyperglycemia)?
somogyi effect - detected by glucose curve
What type of glucose decrease will give “central” neural signs of hypoglycemia?
slow decrease
What is the MOA of sulfonylureas?
stimulate release of insulin from B cells
What is an example of a sulfonylurea? how is it administered?
Glupizide, Glimepiride - oral BID
What is the source of biguanide drugs?
Galega officinalis (Goats rue)
What is an example of a biguanide?
metformin - decrease GI uptake of glucose
What type of drug is acarbose? why isnt it used as much in humans?
alpha-glucosidase inhibitor - many GIT SE
What are incretins secreted from? What stimulates their secretion?
Secreted from GIT, stimulated by food
What are 2 major incretins?
GLP-1 - increase insulin, decrease glucagon
GIP - increase insulin release
Exenatide is derived from what?
gila monster saliva
How is DPP-4 related to GLP-1?
DDP-4 =degrades incretins
What is an amylin agonist analogue example?
pramlintide
What 3 things does pramlintide do in humans?
slows gastric emptying, prevents rise in glucagon, satiety