Term
Failure to regulate normal blood glucose concentrations results from what? |
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Definition
1. Insulin deficiency 2. Reduced ability of tissues to respond to insulin AND impaired insulin secretion that can't overcome resistance |
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Term
True or false? Diabetes mellitus is common only in dogs. |
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Definition
False - DM is common in both dogs and cats |
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Term
What are the two major forms of diabetes mellitus? |
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Definition
Type 1 - insulin dependent Type 2 - non-insulin dependent diabetes |
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Term
What is the usual age of onset of DM in dogs? |
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Definition
4-14 years, peak 7-9 years |
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Term
What is the main defect in Type I diabetes? |
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Definition
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Term
What are the TWO main defects of Type 2 diabetes? |
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Definition
Insulin resistance and inadequate B-cell function |
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Term
What are some characteristics of Type 2 diabetes? |
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Definition
1. Target tissues insenstive to insulin 2. Pancreatic and plasma insulin levels elevated early in dz, later decrease and become insulin-dependent. 3. Pancreatic insulin secretion always abnormal (insulin low wrt plasma glucose 4. 30-50% cases in cats |
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Term
What are some characteristics of Type 1 diabetes? |
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Definition
1. Pancreatic insulin low or absent; absolute exogenous insulin req. 2. Strong genetic/breed component; most DM in dogs is Type 1 3. Most often results from AI-mediated destruction of B-cells 4.Islet destruction 2ndary to pancreatitis in dogs |
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Term
What are some risk factors for diabetes in cats? |
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Definition
Age (old>young) Gender (M>F) Neutering (incr risk for obesity) Physical activity (low --> obesity) Breed (Burmese) Drugs (corticosteroids, megestrol acetate) |
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Term
True or false? Type 2 diabetes is well-described in dogs. |
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Definition
False Not well described in dogs, but IR related to obesity could contribute to other forms. |
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Term
The prevalence of diabetes in dogs increased _____ from 1970-1998 |
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Definition
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Term
50% of classical Type 1 diabetes in dogs is due to what? |
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Definition
Autoimmune B-cell destruction |
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Term
30% of diabetes in dogs is secondary to pancreatitis. How? |
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Definition
Pancreatic islet cells destroyed along with endocrine tissue. |
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Term
Cushing's and GC therapy lead to diabetes resulting from what? |
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Definition
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Term
True or false? Diestrus- or pregnancy-associated diabetes is uncommon in dogs. |
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Definition
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Term
True or false? Diabetes is fairly common in horses. |
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Definition
False - only a number of case reports |
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Term
Equine cases of diabetes are usually secondary to what diseases? |
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Definition
Cushings & pituitary adenomas |
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Term
Unlike dogs, horses with Cushing's do not usually develop ____ unless they also have ___________. |
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Definition
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Term
Horses can develop diabetes in the absence of Cushing's with loss of what? |
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Definition
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Term
What are clinical features of DM? |
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Definition
1. Hyperglycemia 2. Glycosuria 3. Polyuria/polydypsia 4. Polyphagia/hyperphagia 5. Ketosis |
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Term
How is diabetes diagnosed? |
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Definition
1. Clinical signs (PU/PD, hyperphagia, weight loss) 2. Hyperglycemia (r/o other causes) 3. Low/absent insulin or C-peptide 4. Oral glucose tolerance test (OGTT)- human px and type 2 |
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Term
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Definition
1. 37 AA peptide co-stored and secreted along with insulin in B-cells 2. Forms amyloid deposits in cats, monkeys, humans. Plaques can be involved in pathology of islet lesions in type II 3. Influences blood glucose & appetite by inhibiting gastric emptying |
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Term
How do you treat type 1 diabetes? |
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Definition
1. Administration of insulin 2. Goal of treatment to achieve optimal control of both fasting and fed glucose levels while avoiding hypoglycemia 3. Long-term treatment success can be assessed from HbA1c or fructosamine 4. Various types of insulin with different onset and durations of action (most of human recombinant origin) |
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Term
How do you treat type I diabetes in cats? |
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Definition
Diet, weight loss, hi protein diet (not dietary fiber). Treatments other than insulin fairly limited, possible glipizide and glyburide. Liver enzymes elev. can occur |
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Term
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Definition
Highly acidic ketone bodies. Severe ketosis exceed buffering capacity of blood -> metabolic acidosis -> depress CNS/coma, life-threatening. Usually result of type I. Counterregulatory stress hormones have an important role in DKA. |
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Term
What are some vascular complications of diabetes? Why are there fewer complicatons in animals? |
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Definition
Retinopathy, neuropathy (cats), macrovascular dz. Take years to develop, longer than animal lifespans |
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Term
How can progression of diabetic complications be slowed? |
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Definition
Rigorous control of blood glucose levels. |
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Term
What is the definition of hypoglycemia? |
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Definition
Humans, dogs, cats < 50-60; severe <30 |
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Term
What are causes of hypoglycemia? |
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Definition
Insulin excess in diabetic therapy Insulin secretion by pancreatic B-cell tumor. Prolonged fasting in young animals. Severe infection. |
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Term
What is the first line of defense in restoring normal plasma [glucose]? |
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Definition
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Term
What are signs of hypoglycemia? |
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Definition
Hunger, drowsiness/decreased mentation, sweating, palpitations, convulsions, coma/brain damage |
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Term
What happens with repeated bouts of hypoglycemia? |
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Definition
Awareness of hypoglycemia and counter-regulatory mechanisms are impaired |
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Term
What kinds of hormones have an important role in DKA? |
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Definition
Counter-regulatory stress hormones |
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Term
How does hypoglycemia occur in insulin-treated animals? |
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Definition
Insulin overdose; animal does not eat or vomits after usual insulin dose; strenuous exercise, impaired counter-reg responses (glucagon, epi) |
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Term
What is the major limiting factor that prevents achieving good glycemic control (and thereby reducing complications)? |
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Definition
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Term
What is the basic functional unit of the thyroid gland? What kind of cells make up the wall of this unit? |
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Definition
Follicle; cuboidal follicular cells when inactive, columnar when active |
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Term
What is the composition of the thyroid gland? |
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Definition
2 separate lobes, lateral to first 5-8 tracheal rings. Lobes made of lobules separated by fibrous stroma |
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Term
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Definition
Contained in the follicular lumen, viscous gel that stores thyroglobulin |
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Term
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Definition
large glycoprotein containing Tyr residues and iodotyrosines that are precursors for thyroid hormone synthesis |
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Term
How are thyroid hormones derived? |
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Definition
Iodination of tyrosine molecules |
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Term
How is iodide metabolized in the thyroid? |
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Definition
Active transport from ECF into follicular cell --> oxidized by thyroid peroxidase, incorporated into Tyr residues in thryoglubulin --> MIT and DIT |
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Term
Iodothyrines are formed from coupling of ________ and _________. |
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Definition
MIT (monoiodotyrosine) and DIT (diiodotyrosine) |
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Term
What are the thyroid hormones and what are the chemical differences? |
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Definition
T4, T3 and rT3, differences relate to number and location of iodides on Tyr molecule |
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Term
What accounts for most of the thyroid hormone secreted by the thyroid gland? |
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Definition
T4 (thyroxine), small quantities T3, minor amts rT3 |
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Term
Thyroglobulin containing _____, _____, ____, ____, and ____ is stored extracellularly as ________ in the follicular lumen |
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Definition
MIT, DIT, T3, rT3, T4 Colloid |
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Term
What is the prerequisite for thyroid hormone secretion? |
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Definition
Thyroglobulin must re-enter thyroid cell and undergo proteolysis. |
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Term
How does thyroid hormone secretion occur? |
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Definition
Cellular uptake of colloid (containing Tg) by endocytosis, colloid droplets fuse with lysosomes, proteases hydrolyze Tg --> thyroxine (T4)and a little T3 and Tg "diffuse" into circulation |
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Term
What is the cause of feline hyperthyroidism? |
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Definition
Blocks thyroid hormone secretion by inhibiting thyroid peroxidase |
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Term
What percent of T3 and T4 are bound to plasma proteins? What are some of those proteins? |
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Definition
99%, thyroid hormone-binding globulin (TBG), thyroxine binding prealbumin (TBPA), lipoproteins |
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Term
What are the biologically active thyroid hormones? What are their effects? |
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Definition
Unbound/free T3 and T4 Negative feedback inhibition on pituitary TSH secretion; capable of entering cells throughout the body |
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Term
What is the function of protein-bound T4 and T3? |
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Definition
Act as reservoir and buffer to maintain steady concentration of free hormone in plasma, despite rapid changes in delivery of thyroid hormones to tissues |
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Term
What serum T3 and T4 concentrations are usually measured by commercial analyzers? |
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Definition
Sum of protein-bound AND free levels, unless "free T3" or "free T4" specifically requested |
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Term
What happens to T4 inside the cell? |
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Definition
Deiodinated to T3 or rT3 depending on needs of tissue at the time |
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Term
When is T3 preferentially produced? rT3? |
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Definition
T3 = normal metabolic states rT3 (inactive) = illness, starvation, catabolism |
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Term
Why is T3 believed to be the primary hormone that induces physiological effects? |
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Definition
1. Greater biological activity and volume of distribution compared to T4 2. Preferential deiodination to T3 within cell 3. Presence of specific intracellular receptors for T3 |
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Term
What is the major pathway of T4 metabolism? |
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Definition
Progressive deiodination of molecule: outer ring --> T3, inner ring --> rT3 |
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Term
What is the pivotal regulatory step in determining thyroid hormone biological activity? What enzyme does this? |
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Definition
T4-->T3 (outer ring) is step up, T4-->rT3 (inner ring) is step down. Iodothyrine deiodinase |
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Term
What percent of T3 is produced in the thyroid? How is the rest derived? |
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Definition
20% in thyroid, 80-90% from outer ring monodeiodination in peripheral tissue |
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Term
What tissues concentrate most of thyroid hormone? |
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Definition
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Term
What is another metabolic pathway for thyroid hormone? |
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Definition
Conjugation to soluble glucuronides and sulfates --> excretion in bile and urine |
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Term
What are some metabolic processes affected by thyroid hormone? |
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Definition
1. Concentration and activity of enzymes 2. Metabolism of substrates, vitamins and minerals 3. Secretion and degradation of most other hormones 4. Response of target tissues to their hormones 5. Fetal development (neural, skeletal) |
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Term
What processes are stimulated by thyroid hormones? |
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Definition
Calorigenesis, protein/enzyme synthesis, carb & lipid metabolism (synthesis, mobilization, degradation) |
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Term
Do thyroid hormones have any effect on the heart? how about respiratory centers? |
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Definition
Yes, both ionotropic and chronotropic effects. Yes, necessary for normal hypoxic and hypercapnic drive |
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Term
True or false? Thyroid hormones have no effect on RBC production. |
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Definition
False, stimulate erythropoiesis |
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Term
How does thyroid hormone influence bone? |
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Definition
Stimulates bone turnover, increasing formation and resorption |
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Term
How is thyroid hormone synthesis regulated? |
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Definition
Extrathyroidal (thyrotropin) and intrathyroidal (autoregulatory) mechanisms |
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Term
What would demonstrate a perfect case of canine hypothyroidism? |
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Definition
Low thyroid hormone levels Positive thyroglobulin test |
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Term
What are the types of thyroxine deiodinase? |
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Definition
Type 1 - outer and inner ring Type 2 - outer ring (T3, step up) Type 3 - inner ring (rT3, step down) |
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Term
What would demonstrate a perfect case of canine hypothyroidism? |
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Definition
Low thyroid hormone levels Positive thyroglobulin test |
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Term
Name three physiological effects of thyroid hormones. |
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Definition
1. O2 consumption and BMR 2. Cardiac contractility and HR 3. Fn of respiratory center 4. RBC production 5. GI motility |
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Term
Name three physiological effects of thyroid hormones. |
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Definition
6. Bone metabolism and resorption 7. Synthesis of structural proteins 8. CNS development 9. Cholesterol and lipid metabolism |
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Term
What are tests that assess thyroid gland function? |
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Definition
Total T4 and free T4 Endogenous TSH Total T3, free, T3, rT3? |
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Term
What is the test for lymphocytic thyroiditis? |
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Definition
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Term
What is the initial treatment for canine hypothyroidism? |
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Definition
Synthetic T4 (Na levothyroxine) Synthetic T4 normalizes T4, T3 and TSH. Synthetic T3 results in normal T3 but non-detectable T4 and TSH. |
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Term
How do you test for feline hyperthyroidism? |
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Definition
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Term
What is the effect of increased TSH? Decreased TSH? |
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Definition
Decreased thyroxine --> hypothyroidism (dog) Increased thyroxine --> hyperthyroidism (cat) |
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Term
What inhibits TSH secretion at the pituitary? |
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Definition
T3 produced locally by monodeiodination of T4 |
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Term
Describe extrathyroidal regulation. |
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Definition
Positive-negative feedback loop in pars distalis (anterior lobe) of pituitary and follicular cells of thyroid gland. Increased thyrotropin (TSH) --> thyroid secretion, increased thyroid hormone secretion --> suppresses pituitary TSH |
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Term
What modulates the "thermostat" setting of the thyroid hormone-TSH feedback loop? |
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Definition
TRH (thyrotropin-releasing hormone) from hypothalamus |
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Term
What are examples of autoregulatory mechanisms (independent of TSH)? |
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Definition
1. Wolff-Chaikoff block (decrease Tg iodination and hormone synthesis w/out increasing iodide intake) 2. Intrathyroidal alterations in thyroid sensitivity to TSH stimulation 3. Increased ratio of T3:T4 secretion during iodide deficiency |
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Term
What is hypothyroidism and what usually causes it? |
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Definition
Deficiency in thyroid hormone production, usually by immune-mediated or neoplastic destruction of thyroid gland |
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Term
What are clinical signs of hypothyroidism? |
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Definition
Changes in mentation (lethargy), metabolic rate (weight gain), skin (alopecia, seborrhea, pydoderma), NM system (weakness) |
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Term
What is hyperthyroidism and what usually causes it? |
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Definition
Excess of hormone production/secretion, caused by functional tumor or (in cat) adenomatous hyperplasia |
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Term
What are clinical signs of hyperthyroidism? |
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Definition
Hyperactivity, polyphagia, weight loss, tachycardia, aggression |
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Term
How do we clinically assess the function of the thyroid gland? |
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Definition
Measuring baseline serum thyroid concentrations or evaluating response to provocative stimulation (TSH test) |
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Term
What tests are recommended for assessment of thyroid gland function in animals with suspected thyroid dz? |
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Definition
Serum total and free T4 Measurement of TSH where validated assay exists |
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Term
Is serum T3 a good gauge of thyroid gland function? Why or why not? |
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Definition
Most T3 and rT3 formed in extrathyroidal sites and intracellular (not in plasma) and minimal amt secreted by thyroid |
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Term
What is the biologically active form of calcium? |
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Definition
Ionized (50% of the 1% in ECF), this part under regulation and control |
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Term
What are the hormonal regulatory mechanisms? |
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Definition
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Term
What are some of the primary functions of Ca ions in the body? |
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Definition
NT release, membrane perm, muscle contraction, blood coagulation, enzyme activation, intracell. 2nd messenger, hormone release, bone formation, cell motility, cell secretion, cell differentiation |
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Term
What form is calcium in the bone? |
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Definition
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Term
Calcium ______ is most important for biological processes. |
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Definition
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Term
What are the major functions of phosphate? |
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Definition
Major intracellular anion, cell membrane component (phospholipids), ADP/ATP, regulates enzymes/protein formation, urinary buffer |
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Term
What are the primary functions of Mg ions in the body? |
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Definition
Enzyme activation (cofactor), suppress Ca release from SR, regulation of protein synthesis, complexes with ADP/ATP, structural component bones teeth |
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Term
What is the most important factor regulating PTH secretion? |
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Definition
Plasmic ionic Ca concentration |
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Term
When is daily calcium turnover positive? |
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Definition
Intake/retention > urinary/intestinal loss (childhood skeletal growth, Px/lactation) |
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Term
When is daily calcium turnover negative? |
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Definition
Aging, osteoporosis, hi bone remodeling |
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Term
What is the function of PTH? |
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Definition
Works via vitD and calcitonin to regulate blood Ca and P concentration |
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Term
Which cells in the parathyroid secrete PTH? |
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Definition
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Term
What is the structure of the parathyroid gland? |
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Definition
85 AA linear peptide, preproPTH is 115 AA cleaved at N-term --> proPTH --> PTH. Stored in vesicles |
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Term
How do PT chief cells regulate PTH secretion? |
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Definition
1. Detect Ca changes of only a few % 2. "calciostat" sensing 3. Low Ca stimulates secretion 4. High Ca inhibits secretion 5. Responds in seconds 6. Sufficient PTH to sustain 60-90 sec response |
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Term
What kind of receptor is the PTH receptor? |
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Definition
Cellular membrane receptor (binds to outside cell, unlike vitD) |
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Term
PTH secretion acts on what organs? |
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Definition
Kidney, bone, intestine (indirectly) |
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Term
What is the effect of PTH on bone? |
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Definition
Stimulates calcium (and phosphate) release (via vitD); breaks down bone |
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Term
Can PTH lead to bone formation? |
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Definition
Yes, intermittent administration |
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Term
What are the effects of PTH on the kidney? |
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Definition
Conservation of Ca by kidney: increases tubular re-absorption of Ca, increases phosphate excretion by inhibiting uptake (prevents phos release from bone), increases bicarb excretion = acidosis (decreases Ca binding albumin --> increases free plasma ionic Ca), stimulates enzyme that activates vitD |
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Term
What is the main function of vitD and bone? |
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Definition
Mineralization of Ca to bone; when Ca low, PTH goes up --> increases RANKL --> osteoclasts |
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Term
What is the effect of plasma Ca on PTH? |
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Definition
Ca presence in bloodstream has direct negative feedback to (shut off PTH) decrease bone breakdown/resorption |
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Term
What is the action of activated vitD? |
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Definition
Facilitates absorption of Ca and P by intestine |
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Term
How is calcitonin secretion controlled? |
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Definition
Released in response to small increases in plasma ionic [Ca] Physiological ANTAGONIST of PTH - inhibits osteoclasts (calcitonin disorder = no serious problem) |
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Term
What is primary hyperparathyroidism? |
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Definition
Problem in gland, excessive PTH release (usually PTH adenoma, rare hyperplasia). Start with NORMAL Ca |
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Term
What is secondary hyperparathyroidism? |
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Definition
Compensatory mechanism to maintain serum Ca, can cause hypercalcemia, PTH gland can hypertrophy |
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Term
What are the results of hyperparathyroidism? |
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Definition
Hypercalcemia, rickets in young animals, osteomalcia in adults |
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Term
What are signs of hypercalcemia? |
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Definition
Bone dissolution, pain or fracture Kidney stones Constipation, anorexia, fatigue, muscle weakness |
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Term
What is hypoparathyroidism? |
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Definition
Deficiency in PTH resulting in hypocalcemia. Can be complication of sx, autoimmune, or congenital PTH resistance |
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