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