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554 Cards in this Set
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- Back
- 3rd side (hint)
Pancreatic Anatomy |
-V-shaped |
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Pancreatic Histology
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-LOTS of exocrine pancreatic ducts |
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Pancreas Exocrine Function
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-Digestive enzymes
-Bicarbonate -Secretes through pancreatic ducts |
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Pancreas Endocrine Function
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-Secretes hormones
-Insulin (Beta cells) -Glucagon (Alpha cells) -Somatostatin (Delta cells) -Pancreatic polypeptide (F cells) -Each hormone is secreted from a different cell type within the islet of langerhans |
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Insulin Synthesis
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-Synthesized and Secreted from B-cells in endocrine pancreas
-2 introns and 3 exons -A chain -B chain -C chain |
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Insulin C peptide
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-“Connecting peptide” |
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Function of Insulin on Carbohydrate metabolism
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-Anabolic Hormone
-Increases glucose entry into muscle and adipose tissue --no insulin, blood glucose increases -Increases glucagon synthesis in liver -Decreases gluconeogenesis in liver |
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Function of Insulin on Protein metabolism
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-Insulin is Anabolic
-Increases amino acid uptake in muscle -Increases protein synthesis in muscle and liver -Decreases protein catabolism in muscle |
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Functions of Insulin on Fat metabolism
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-Insulin is Anabolic
-increases lipid synthesis in adipose tissue and liver -Decreases ketogenesis -Activates lipoprotein lipase -Inhibits hormone-sensitive lipase |
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Lipoprotein Lipase
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-Chops off fatty acids and stores in fatty tissue
-Anabolic process, activated by insulin |
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Hormone Sensitive Lipase
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-Located within fat tissue
-When activated, lyses fat stores into fatty acids -Catabolic activity -Inhibited by insulin |
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Other Actions of Insulin
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-Increases cell growth |
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Secretion of Insulin
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-Stimulated by:
--glucose, mannose, fructose --amino acids --Glucagon --Intestinal hormones: gastrin, secretin, cholecystokinase |
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Glucagon
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-Antagonistic to insulin
-breaks down glycogen to glucose -Stimulates insulin secretion, if more glucose is made it needs to be transported into cells by insulin -Inhibited by insulin |
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Counter-regulatory hormones of Insulin
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-“Diabetogenic hormones”
-increase blood glucose concentration -Glucocorticoids -Glucagon -Catecholamines -Growth Hormone |
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Actions of Glucagon
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-Catabolic action
-Increases glycogenolysis, breakdown of glycogen -Increases lipolysis, breakdown of fats --Increases ketone body formation -Increases gluconeogenesis, formation of glucose |
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Fed state
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-Insulin kicks in to store material just ate
--increased glucose oxidation --increased glycogen synthesis --increased fat synthesis --Increased protein synthesis -Anabolic state |
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Fasted State
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-Glucagon kicks in and dominates
-Uses energy stores to give energy needed -Catabolic state --increased Ketogenesis --Increased gluconeogenesis --Increased glycogenolysis |
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Actions of Somatostatin
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-Internal regulator of pancreatic hormone secretion
-Inhibits secretion of insulin, glucagon, pancreatic peptide secretion -Slows gastric emptying -Decreases gastric acid secretion |
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Actions of Pancreatic Polypeptide
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-Very little is known
-Secreted from intestinal cells, not pancreas -Slows absorption of food from GI tract -Inhibits gallbladder secretions -Inhibits intestinal motility -Inhibits pancreatic secretion |
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Glucose Transport into Cells
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-Na-glucose cotransporters
-Glucose transporters |
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SGLT-2
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-in kidneys
-absorbs glucose from proximal renal tubules -Takes glucose out of the kidney filtrate and back into body -when overwhelmed, glucose ends up in urine -High affinity for substrate |
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SGLT-1
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-in intestine
-High affinity for substrate -Genetic defect causes diarrhea, can be fatal if not corrected quickly --glucose stays in intestine, acts as osmotic agent and pulls water into intestine --causes diarrhea |
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GLUT-2
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-Located in beta cells in pancreas
-Low affinity for glucose --prevents aberrant secretion of insulin and hypoglycemia -Increased expression with hyperglycemia -Hyperinsulinemia decreases expression |
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GLUT-1
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-HIGH affinity for glucose
-Located in RBCs, kidney, glial cells of BBB -Also in fetal tissues -In tissues that NEED glucose! |
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GLUT-4
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-In skeletal muscle, hear tissue, fat tissue
-Expression is stimulated by insulin and exercise --exercise increases GLUT-4 -High affinity for glucose |
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Diabetes mellitus
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-Diabetes= polyuria
-Mellitus= sweet |
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Type I diabetes mellitus
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-Insulin dependent Diabetes, need to give exogenous insulin
-Juvenile, affects children --can also be latent autoimmune diabetes in adults (LADA) -Immune mediated disease? -most common form of diabetes mellitus in dogs and cats --ALL dogs need exogenous insulin --most cats need exogenous insulin -Beta-cell destruction -Impaired insulin secretion (hypoinsulinemia) -Can be genetic, immune-mediated, infectious, toxic, or due to some other factor |
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Type II diabetes mellitus
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-Non-insulin dependent diabetes
-Do not need to give exogenous insulin, can treat with other approaches -Uncommon in cats, rare in dogs -Insulin resistance and impaired insulin secretion --may or may not have beta cell destruction -Insulin concentration may vary, can be high, medium, or low --if high, indicates type II -Obesity, islet-cell amyloid deposition, genetic, other factors may be involved -Older individuals are affected -Associated with increased BMI in humans --Now are starting to see in young children also |
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Genetic component of human Type I diabetes mellitus
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-MHC genes
--code for human leukocyte antigen class II proteins -HLA proteins present pancreatic peptide proteins to T-cells, T-cells destroy proteins |
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Canine Diabetes
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-All are hypoinsulinemic
--all need insulin -Some have anti-pancreatic beta cell antibodies when diagnosed --not sure if antibodies have caused destruction or formed secondary to destruction via different mechanism -Breed predisposition may imply genetic component |
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Obesity and Insulin Resistance in cats
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-Obese cats are 4x as likely to develop diabetes
-Diabetic cats are considered to be THIN --no anabolic protein, no storage of glucose -Hyperglycemia and increased insulin secretion are associated with weight gain -Cat may start out as obese, but due to lack of insulin will become thin -Obesity in cats may be associated with insulin resistance -Obesity induced insulin resistance may be reversible if body condition returns to normal |
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Mechanisms for Obesity Associated Insulin Resistance
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-Down-regulation of GLUT-4 |
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Down-regulation of GLUT-4 and diabetes
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-Exercise and insulin concentration can increase expression of GLUT-4
--more able to transport glucose into cells -In obesity, down-regulation of GLUT-4 -If cat is put on an exercise regime, can increase GLUT-4 and decrease insulin resistance |
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Amyloid Deposition and Diabetes in Cats
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-Amyloids: synthesized from islet amyloid polypeptie
-Secreted with insulin -Deposited in beta cells --deposited in diabetic cats (70%) and non-diabetic cats (35%) -Deposition in beta cells causes destruction of beta cells -Decreases insulin secretion -increases insulin resistance -AA sequence that forms amyloid is important for deposition in beta cells --Cats and humans: 25-29 sequence allows for reposition of amyloid in beta cells --In rodents, has slightly different sequence that does not allow deposition -Dogs have the same sequence as cats but do not get amyloid deposition because they do not have hyperinsulinemia with diabetes (hypoinsulinemia) --only occurs with insulinoma |
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Genetic components in Human Type II diabetes mellitus
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-Different from type I genetic predispositions
-Mutations in insulin genes, insulin receptor, IRS-1, Glucokinase, Glycogen synthase, Mitochondrial DNA |
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Genetic component in feline Diabetes mellitus
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-Burmese cats in Australia are predisposed
--only in Australia |
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Secondary Diabetes Mellitus
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-Secondary to progesterone concentrations
-Progesterone causes increased secretion of GH -GH is diabetogenic, counter-regulatory for insulin -In dogs: --diestrus, Pregnancy -In cats: --megestrol acetate |
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Transient Diabetes Mellitus
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-Diabetes that comes and goes
-Rare in dogs, uncommon in cats -Can be due to treatment with drugs that cause hyperglycemia -Subclinical diabetes mellitus that is complicated by concurrent disorder or drug -Animal is “teetering on edge” of diabetes and drug administration “pushed into diabetes” -Can be caused by any disease that causes stress and induces stress hormones --glucocorticoids, glucagon, catecholamines, Growth hormone |
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Concurrent Diseases and Diabetes
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-Any concurrent disease process causes stress
-Causes release of stress hormones --glucocorticoids, glucagon, growth hormone, catecholamines -Counter-regulatory for insulin, can push a pancreas into diabetic state for a while |
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Glucose and Insulin secretion suppression
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-Glucose itself is toxic to the pancreas
-High amounts of glucose and suppress insulin secretion -Stress or underlying disease can cause glucagon release and high glucose levels --will inhibit insulin release from pancreas |
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Clinical Presentation of Diabetes
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-Uncompilcated diabetes mellitus
-Diabetic ketoacidosis -Hyperosmolar non-ketotic diabetes mellitus |
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Uncomplicated diabetes
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-Office visit
-There is a problem, but there is time -In dogs, occurs at 7-9 years -In cats, 10 years -Samoyeds and Australian shepherds are predisposed -Burmese cats are at increased risk -Pitts, goldens, and german shepherds are no disposed -Keeshunds get genetic form of disease, autosomal dominant -intact and neutered female dogs are at increased risk -Neutered males are at increased risk |
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History and Clinical signs of uncomplicated diabetes
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-PU/PD
-Weight loss -Polyphagia -Blindness (dogs) -Plantigrade stance (cats) -Anorexia -Vomiting |
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Cataracts and Hyperglycemia
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-Glucose and fructose diffuse into the lens
-Fructose is stuck in the lens, cannot get out -Draws water into the lens, lens swells and damages lens fibers -In dogs, high concentration of aldose reductase in lens --causes conversion of glucose to fructose -cats do not have high concentration of aldose reductase in lens, do not get cataracts so much |
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Physical exam for uncomplicated diabetes
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-Vary from normal to severely compromised animals
-May be non-sepcific -Variable body weight --underweight, normal, or obese --depends on stage of disease -Variable hydration status, normal or dehydrated -hepatomegaly due to fatty lipidosis -Cataracts (dogs) -Plantigrade stance (cats) -Lethargy, weakness -Acetone breath |
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Plantigrade Stance and Diabetes
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-Common in Cats
-Fructose gets into nerves and cannot get out? Aldose reductase in nerves? |
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History, clinical signs, and PE for uncomplicated diabetes are affected by concurrent disease
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-UTI
-Hyperadenocorticism -Acute pancreatitis -Hypothyroidism -Neoplasia -Other infections -Look for these diseases when diabetes becomes dysregulated! Common cause of complications with diabetes |
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UTI and Diabetes
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-Common finding that can complicate diabetes
-Glucose is excellent medium for bacterial growth -When urine is dilute, preventative mechanisms for bacteria are gone -Neutrophils in diabetic state are compromised --cannot adhere to the antigen -Most common reason an uncomplicated case of diabetes becomes complicated -Infection can increase dysregulatory hormones and decrease insulin secretion |
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Hyperadrenocorticism and Diabetes
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-Cushing’s disease and diabetes are not related pathophysiologically
-Related how they affect the body -Both occur in middle-aged, older individuals -Increased glucocorticoid secretion causes insulin resistance -Clinical signs and parameters are very similar to each other |
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Acute Pancreatitis
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-Occurs with diabetes, cushing’s and hypothyroidism
-All 3 cause hypercholesterolemia -high-fat diet will induce pancreatitis -Not sure that high cholesterol is the reason 3 diseases cause acute pancreatitis, but makes sense |
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Hypothyroidism
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-Endocrine disease that does not cause PU/PD
-causes hypercholesterolemia -Immune-mediated disease -Commonly seen with diabetes |
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Diagnosis of Diabetes mellitus
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-History and clinical signs
-Physical exam findings -Persistent hyperglycemia --cats can have hyperglycemia due to stress, need to make sure hyperglycemia is persistent! -Glucosuria |
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DDx for PU/PD
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-Renal disease
-Liver disease -Diabetes mellitus -Hyperadrenocorticism -Hyperthyroidism -Hypoadrenocorticism -Hypercalcemia -Hypokalemia -Glucocorticoid administration -Diuretics -Anticonvulsants -Fluid overload -Pyometra -Diabetes insipidus -Psychogenic -Polycythemia |
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Renal disease and PU/PD
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-Tubular disease: tubules do not concentrate urine as they should
-Glomerular disease: small proteins leak through glomerulus --specifically albumin --act osmotically, draw water into tubule lumen |
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Liver disease and PU/PD
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-Liver produces urea and BUN
-BUN is needed to concentrate urine across tubules |
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Diabetes and PU/PD
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-Blood glucose spills over into renal tubules when elevated
-Acts as an osmotic agent |
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Hyperadrenocorticism and PU/PD
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-Glucocorticoids bind ADH receptor in kidney
-Prevents ADH from binding to receptor -no ADH binding, no ADH effect, diuresis results |
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Hyperthyroidism and PU/PD
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-Thyroid hormone increases metabolic demand
-Increases O2 demand and O2 flow -Increases blood flow throughout the body -Increases blood flow to kidneys, causes increased GFR and PU/PD |
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Addison’s disease and PU/PD
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-Hypoadrenocorticism
-Lack of glucocorticoids and aldosterone -Na is secreted in excess in urine -Na acts as osmotic agent and draws water into tubular lumen |
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Hypercalcemia and PU/PD
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-Can develop as a result of many disorders
--primary hyperparathyroidism --tumors --fungal diseases --idiopathic -Ca binds to ADH receptors and prevents ADH binding -No ADH effect |
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Hypokalemia and PU/PD
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-K is needed for concentration across renal tubules
-No K, no concentration and PU/PD results |
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Pyometra and PU/PD
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-E. coli endotoxin is toxic to renal tubules
-Causes polyuria |
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Diabetes Insipidus and PU/PD
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-Primary: ADH is not secreted from pituitary
-Secondary: ADH is present but cannot bind to receptor in renal tubules -Decreased ADH secretion from pituitary -or ADH is not binding to its receptor because glucocorticoids block receptor |
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Common DDx for weight loss in the face of polyphagia
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-Diabetes Mellitus
-Hyperthyroidism -GI parasites -Exocrine pancreas insufficiency -Protein losing enteropathy -Protein losing nephropathy |
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Polypagia and Diabetes mellitus
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-Glucose does not enter into satiety center
-No signal is sent to stop eating -Body is also in catabolic state, animal is losing weight |
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Hyperthyroidism and Polyphagia
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-Thyroid hormone increases metabolic demands
-Cat is unable to eat enough to compensate for huge energetic demands |
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Exocrine Pancreatic Insufficiency and Polyphagia
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-No digestive enzymes to digest food, food passes through GI without getting digested
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DDx for Hyperglycemia
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-Diabetes mellitus (really the only good differential)
-Stress (will be transient) -Hyperadrenocorticism -Glucocorticoid administration -Progesterone administration -Megestrol acetate -TPN or other fluid administration -Post-prandial -Diestrus -Pheochromocytoma -Acromegaly (GH secretion) -Acute pancreatitis -Factitious measurement |
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DDx for Glucosuria
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-Diabetes mellitus
-Primary renal glucosuria --defect in Na/Glucose transporter -Very few DDx! |
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Acute pancreatitis and glucosuria
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-Causes high secretion of insulin counter-regulatory hormones
-Especially glucagon -Will cause hyperglycemia |
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Diagnostic Evaluation for Diabetes
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-CBC/Chem: usually normal
-Urinalysis -Urine culture -Serum insulin or C-peptide concentration |
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CBC for patients with Diabetes
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-Usually normal
-Can tell if there is something ELSE wrong with patient -Hematocrit may be normal, low, or high -“Stress leukogram” may be present --mature neutrophilia, monocytosis, lymphopenia, eosinopenia -Neutrophilia with left shift may be present if there is an infection |
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Chem screen for patients with Diabetes
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-Hyperglycemia
-Increases Alanine Aminotransferase activity (ALT) -increased Aspartate aminotransferase activity (AST) -increase alkaline phosphatase activity (ALP) -Lipemia, fat is not being stored -Hypercholesterolemia -Elevated total bilirubin concentration -Azotemia when PU exceeds PD |
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Increase alkaline phosphatase activity with diabetes
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-in epithelial biliary cells
-increases with cholestasis -Increases with stress situations via glucocorticoids |
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Urinalysis for patient with Diabetes
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-Variable specific gravity
-Glucose interferes with USG measurement via spectrometer -May see protein in urine -Bacteriuria -Ketonuria with DKA |
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Urine culture and sensitivity for Diabetes
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-Bacteria and WBCs may not be apparent in urine sediment even if infection is present
-urine is dilute -May not have white cells because WBCs have difficulty migrating to the site of infection and binding bacteria -PU/PD can mask lower UTI signs |
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C-peptide concentration in Diabetic patients
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-Type I: C-peptide is low
--cannot distinguish type I from type II with low C-peptide concentration -Type II: C-peptide is variable |
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Treatment of Diabetes Mellitus
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-Insulin
-Deit -Exercise -Oral hyperglycemics -treatment of concurrent disease |
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Goal of Insulin Treatment
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-Want to mimic physiologic action of insulin in the body
-Produce something similar to 1st phase and 2nd phase insulin secretion |
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Normal insulin secretion
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-GLUT-2 recognizes glucose in blood when it is higher than 60mg/dL
-Glucose enters beta cell and is metabolized, forms ATP -K channels close when glucose forms ATP --Intracellular K concentration increases --voltage of the cell increases -Voltage-dependent Ca channels open --Ca flows into the cell, concentration of Ca increases -Causes Insulin exocytosis, secretion of Insulin |
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Biphasic secretion of Insulin
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-1st phase: rapid and short
--Ready to release insulin granules, already adhered to beta cell membrane --high magnitude --5 minutes --goal is to reach a steady state of insulin -2nd phase is longer --45-60 minutes --Goal is to maintain steady state of insulin |
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Ready to Secrete Insulin granules
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-Are embedded within the beta-cell membrane
-Ready to be secreted as soon as glucose enters the beta cell -Allows 1st phase of insulin secretion to occur rapidly and end rapidly |
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Basal-bolus insulin therapy in Humans
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-Humans administer basal insulin that mimics 2nd phase of insulin secretion
-Before meals, give boluses of rapid, short-acting insulin that mimics 1st phase |
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Species variation in Insulin
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-Insulin between species is very similar
-Sub-species of insulin is based on species and duration of action -Porcine insulin is identical to dog insulin -Short, intermediate, and long acting insulin -Human insulin is genetically engineered and modified to look different from human insulin |
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Short-acting Insulins
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-Regular insulin
-Lispro insulin (Genetically modified insulin, position 28 and 29 switch) -Aspart Insulin (Aspartic acid substitution for proline at position 28) -Glulisine insulin (Glutamic acid at position 29 and lysine added at B3) -All are genetically modified human analogs of insulin -All are clear and colorless -All have 100 units of insulin per ml (human insulin) --veterinary insulin has 40 units per ml |
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Onset and duration of short-acting insulins
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-Shorter and faster than natural insulin products
-5-15 onset of action compared to 30-60 minute onset -4-6 hour duration compared to 8-10 hours duration -have been specifically designed to be faster --designed to be given just prior to the meal -In vet medicine, short-acting insulin can be used for dogs with DKA --faster resolution of DKA, glucose normalization, glucose plateau |
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Fructosamine
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-Albumin bound to glucose
-Once glucose reaches a certain threshold, glucose binds to fructose and forms fructosamine |
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Intermediate Acting Insulins
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-NPH
-Lente -rPZI |
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Neutral Protamine Hagedorn (NPH)
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-Produced by recombinant DNA technology
-Uses non-pathogenic laboratory strain of E. coli -Identical to human insulin --comes in 100 units of insulin per ml, human dosage -Has been available for a long term, is in generic form -Cheaper product -Peaks at 2 hours but lasts much longer -in well-regulated dogs intermediate insulin dose can be 0.6 units per kilo |
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NPH in cats
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-Not well-reported
-Good for financial constraints |
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Porcine Insulin Zinc
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-Lente in humans
-Vetsulin in animals -produced from Pigs -FDA approved for dogs and cats -SHAKE well until homogenous before using -Starting dose of 0.5 units per kg twice daily -comes in pen form for easy injections |
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Recombinant Protamine Zinc Insulin (rPZI)
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-Not produced from an animla
-Veterinary product, approved for use in dogs and cats -Identically to human insulin -0.5 units per kg 2x daily |
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Long Acting Insulin
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-Glarginie
-Detemir -Mimic basal insulin secretion -Both marketed for humans, sold in 100 units per ml |
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Glargine
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-Long-acting insulin
-Peakless insulin used in humans -Asparagine at position A21 is replaced with Glycine -2 Arginine residues added to C-terminal of the B-chain at position B30 -Injected in solution with pH of 4 --low pH is important for long duration of action -Cannot be diluted or mixed with ANYTHING -Mimics flat inter-parandial insulin secretion, peakless -Onset in 2-4 hours -Duration of 20-24 hours -Supplemented with rapid and short-acting insulin at meal times -Starting dose of 0.5 units per kg SQ twice per day |
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Glargine in Dogs
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-Good for easy regulation
-Can be used when other insulin products have not worked well -Peak-less insulin in dogs |
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Detemir Insulin
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-“Levemir”
-Long-acting insulin -Approved by FDA -Commercially available in UK -Injected or prepared in neutral pH -Long mechanism of action because it binds to albumin, slowly released from albumin -Usually given every 12 hours -has been reported to cause anaphylactic and allergic reactions in humans --causes local irritation and pain at site of injection -Hard to monitor pain and inflammation in dogs, not worth using -0.1-0.2 units per kg --hard to draw up, has caused overdoses |
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Which insulin is best?
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-The one that works best for the individual animal
-Glargine is best for cats -NPH is most used in dogs --when problems arise with NPH, switch to glargine |
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Frequency of Insulin Therapy
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-Most dogs and cats need twice daily insulin treatment
-Successful treatment with once daily is rare in dog, uncommon in cat -May change with increased use of glargine or detemir -Intermediate acting insulin is given every 12 hours to start -Long-acting insulin can try at 24 hours to start -Initial dose is 0.5 units per kg --except detemir, 0.1-0.2 units per kg --glargine in dogs is 0.3 units per kg -Dose of insulin is adjusted based on glucose curves |
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40 units vs. 100 units
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-Need to look at “fine print” of the insulin syringe!
-If a 40 unit syringe is used with a 100 unit product, will overdose patient! -ALWAYS give insulin in an insulin syringe! |
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Dietary Management with Diabetes
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-Try to have food at a fixed time
-Fixed caloric intake based on fixed amount of insuli -Give diet that will decrease post-prandial blood glucose fluctuations -Weight reduction diet for obese patients -Dietary management for dogs and cats is different -Make sure the owner knows how crucial the diet is! |
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Dietary management of diabetes in Dogs
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-High insoluble fiber diet
--weight loss --slow carbohydrate absorption --decreases post-prandial blood glucose fluctuations --increases insulin sensitivity -Rich in complex carbohydrates --takes time to break down, more gradual glucose release -Fixed protein and restricted fat content -Fixed feeding schedule -Give dogs that do not need to lose weight the same diet, helps regulate the diabetes -Goal is diabetic regulation |
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Details of the feline diet
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-Carnivores
--consume high protein and low carbohydrate diet -Constant gluconeogenesis --energentically expensive process -Possibly no glucokinase in liver and pancreas? |
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Guidelines for dietary management in Cats
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-Need to change diet to something the cat will eat
--if they don’t eat, get hepatic lipidosis --try a variety of diets that the cat will eat -Fixed caloric intake if possible -Maintain optimal body condition -Low carbohydrate diet -High protein diet -Most important is that the cat eats! |
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Exercise management and Diabetes
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-Up-regulates GLUT-4
-Insulin sensitivity is increased with increased blood flow, glycogen synthase activity, and glucose storage as glycogen -In humans increases insulin-stimulated glucose transport and glycogen synthesis |
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Exercise in dogs and cats with Diabetes
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-Exercising cats is difficult
-Diabetic dogs can benefit from exercise --promote weight loss in obese patients --increase blood flow --Possibly increases glucose transport and glycogen synthesis -Need to build up to exercise gradually --adjust food intake on the days that dog exercises --want to avoid hypoglycemia on exercising days --increase exercise 2 minutes every day |
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Oral Hypoglycemics
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-Main use in humans for diabetes type II
-Rare in dogs and cats, not that helpful -increases insulin secretion from beta cells -Binds to GLUT2 receptor on beta cells --causes metabolism and creation of ATP, shuts down K transporter, K builds up and changes charge of cell, Ca voltage-gated channels open, Ca floods into cell and causes release of insulin |
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Sulfonylurea Mode of Action
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-Stimulates insulin secretion from pancreatic beta cells
-Binds to receptors on beta cell membranes and induces ATP-dependent K channels to close -Only works if animal has some type of type II diabetes |
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Adverse side effects of Sulfonylurea in Humans
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-Hypoglycemia
-Allergic reactions -GI intolerance -Hepatotoxicity -Severe dermatitis -Hemolytic anemia -Thrombocytopenia -Agranulocytosis -Hyperinsulinemia and risk for atherosclerosis -May be cardiotoxic |
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Glipizide in Cats
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-Difficult to predict which cats will respond
-Decision to treat with glipizide is based on clinical presentation -only try in cats that are relatively healthy -meant to treat mild hyperglycemia in relatively stable animals -2.5mg PO twice daily for 2 weeks --if still hyperglycemic, increase to 5mg PO twice daily --if still hyperglycemic at 4 weeks, discontinue and treat with insulin -Give orally twice per day |
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Cardiotoxicity of oral hypoglycemic
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-K channels need to be open during ischemic events to promote vasodilation
-If channels in heart stay closed, may worsen myocardial infarctions -Unknown what it does in cats |
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Transdermal Glipizide
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-Not recommended
-inconsistent absorption |
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Adverse effects of Glipizide in cats
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-Vomiting after administration
-Hypoglycemia -Increased serum hepatic enzyme activity -Icterus -Removing the drug causes issues to go away |
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Glipizide in Dogs
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-Has not been reported
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Treatment of Diabetes mellitus
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-Insulin
-Diet -Exercise -Oral hypoglycemic (glipizide) -Treatment of concurrent diseases |
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Home care for the diabetic dog
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-VERY IMPORTANT! Crucial for care of a diabetic dog!
-Note changes in clinical signs, be very observant -Monitor urine glucose twice daily before feeding --ketonuria is an emergency -Not presence or absence of ketones in urine 2x daily -Feed 2x daily -Administer insulin 2x daily after feeding -If dog vomits or does not eat a meal, administer half insulin dose and seek veterinary advice --do not skip insulin injection -If animal seizures, weakness, or signs of hypoglycemia occur, give karo syrup to the gums (on finger onto gums) --indicate hypoglycemia |
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Concurrent diseases and Diabetes
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-Concurrent diseases cause STRESS
-Induces counter-regulatory hormones --glucocorticoids --catecholamines --Growth Hormone --Glucagon |
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Home care for the Diabetic Cat
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-May require free choice food
-Cannot be fasted! Need to eat whatever they will -Sampling urine at fixed times can be difficult -Cats do not like exercise -Monitoring the weight is the best indicator |
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Monitoring response to treatment for Diabetes
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-Monitor clinical signs
--PU/PD --polyphagia --body weight -Monitor glucosuria and ketonuria -perform glucose curves -Measure glycosylated Hb or fructosamine |
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Glucose Curve
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-Needed to determine proper dose of insulin
-only really used if there is a problem with insulin dosage or long time since last glucose curve was done -Measure every 2 hours for at least 12 hours in animals that get insulin daily -Single measurement of blood glucose can not be used to determine dose of insulin |
|
|
Somogyi Effect
|
-Only happens with exogenous insulin, when too much is given
-Catecholamines, glucocorticoids, glucagon, and growth hormone are secreted in response to severe insulin-induced hypoglycemia and cause pronounced hyperglycemia --over-correct for hypoglycemia -Body’s mechanism to counteract hyperinsulinemia and massive drop in glucose -If glucose is too high, need to increase insulin -If glucose is too low, need to decrease glucose |
|
|
Spot glucose measurements
|
-Can be very misleading!
-Have no idea what the glucose was doing for the rest of the day |
|
|
Analyzing a glucose curve
|
-Onset of action: From time 0, when the glucose levels start to decrease
--number of hours after time 0 it takes blood glucose decreases below 250 -Duration of action: Number of hours after time 0 it takes for glucose to return to 250 after it has decreased -Peak action: Time of maximum effect --time point when the blood glucose is the lowest |
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|
Adequate Glycemic Control
|
-Dogs: achieved when blood glucose concentration is between 100-250 mg/dL
-Cats: achieved when blood glucose concentration is between 100-300 mg/dL --assume a cat has some level of stress going on all of the time |
|
|
Insulin Resistance
|
-Suspected when hyperglycemia is present in the face of insulin therapy above 1.5 units/kg per injection
-Something is getting in the way on insulin action |
|
|
Reasons for Insulin Resistance
|
-Improper handling of insulin
--keep in fridge --can be left out overnight, but should not be left out for days -Improper administration of Insulin -Outdated or inactive insulin --do not use if more than 6 months old or opened 6 months ago --activity has probably worn off a little bit -Improper dose or frequency of insulin administration -Poor absorption of insulin -Anti-insulin antibodies -Somogyi effect |
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|
Concurrent Disorders that can cause insulin resistance
|
-UTI
-Pyoderma -Pneumonia -Ketoacidosis -Hyperadrenocorticism (Cushing’s, similar clinical signs to diabetes) -Hyperthyroidism -Hypothyroidism -Acute pancreatitis -Exocrine pancreatic insufficiency -Diestrus -Acromegaly -Renal, liver, cardiac insufficiency -Obesity -Drug induced (prednisone) |
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|
Glycosylated Hemoglobin
|
-Hb that is bound irreversibly to glucose |
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|
Fructosamine
|
-Non-reversible binding of glucose to albumin
-Reflects blood glucose concentration over past 1-3 weeks -Non-enzymatic insulin-dependent bond of glucose to various serum proteins -Use in cats that will not tolerate a blood-glucose curve --not worth the cat freaking out -Can be high with somogyi effect --indicates animal is getting too much insulin -Can also be high if animal is getting too little insulin |
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|
Long-term Complications of Diabetes Mellitus
|
-Cataracts
-Uveitis -Retinopathy -Neuropathy -Nephropathy |
|
|
Diabetes Prognosis
|
-generally good
-Animals do not die from Diabetes, die from other old-age problems -Owner needs to be willing and able to take care of the animal -Quality of life of the animal is good to excellent |
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|
Diabetic Ketoacidosis (DKA)
|
-Complicated diabetes mellitus
-Ketones are synthesized as a substitute form of energy --glucose is not present --body resorts to using fat, ketones are produced -Too much keto-acids result in acidosis and severe electrolyte abnormalities -Acidosis and electrolyte abnormalities can be life threatening |
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|
Assessing ketones
|
-Use keto-stix
-Sticks look for acetoacetate --not the most common ketone body around --most common is beta-hydroxybutyrate -If keto-stix is netagive, does not mean the patient does not have ketones |
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|
Development of DKA
|
-Type I diabetics develop DKA when insulin is 0
-Type II diabetics will not develop DKA because they always have some reserve of insulin -Not the whole story, some dogs with normal insulin will develop DKA |
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|
DKA develops due to another disease
|
-Other disease causes increase in glucocorticoids, glucagon, growth hormone, and catecholamines
-Cause insulin resistance -Insulin resistance pushes patients into DKA -Glucagon is most studied |
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|
Glucagon and DKA
|
-is secreted and remains high in the proper time interval |
|
|
Concurrent disorders and DKA |
-70% of dogs with DKA have confirmed concurrent disorder |
|
|
3 ketone bodies
|
1. beta-hydroxybutyrate
--higher concentrations with increased available hydrogen ions 2. Acetoacetate -Acetoacetate and beta-hydrocybutyrate are in opposite concentrations from each other 3. Acetone --can be smelled on breath Formation of ketone bodies |
-Oxidation of fatty acids
-Made from 2 acetyl CoA or 3 acetyl CoA units |
|
2 Acetyl CoA unit Pathway
|
-2 units of acetyl Co-A can condense to Acetoacetyl CoA in many organs
-Acetoacetyl CoA is converted into acetoacetate --deacylase present in liver only -Acetoacetate is converted to beta hydroxybutyrate and acetone in liver -More acidic environment, more likely to form beta-hydroxybutyrate --does not show up on keto-stick |
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|
3 Acetyl CoA unit Pathway
|
-Acetoacetyl CoA condenses with 3rd unit of acetyl-CoA
--forms 3-hydroxy-3-methylglutary CoA (HMG CoA) -HMG CoA is metabolized to acetoacetate |
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|
Acetyl CoA production
|
-Formed with oxidation of a fatty acid
-Every catabolic action/degradation/oxidation of fat makes Acetyl CoA -Assocaited with lipolysis |
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|
Alteration of Acetyl CoA production in Diabetes mellitus
|
-Decreased insulin action |
|
|
Acetyl CoA summary
|
-Acetyl COA is the precursor for ketone body synthesis
-in Diabetes mellitus, excess synthesis of Acetyl CoA due to excess fatty acid oxidation -Accumulation of Acetyl CoA due to lack of pyruvate synthesis --Acetryl CoA is unable to enter the krebs cycle -Excess synthesis and lack of Acetyl CoA use results in accumulation and conversion to ketone bodies |
|
|
Formation of ketone Bodies
|
-Fasting
-Dehydration -Insulin deficiency -Excess diabetogenic hormones --mostly glucagon --catecholamines --glucocorticoids --growth hormone -Excess diabetogenic hormones are due to concurrent disease or stress |
|
|
Metabolic Acidosis
|
-Formation of keto-acids
-Exacerbated by vomiting, dehydration, and poor renal perfusion |
|
|
Clinical signs of DKA
|
-Chronic untreated diabetes mellitus
--PU/PD, polyphagia, weight loss -Concurrent disease -Acute onset of DKA -Owner will report clinical signs that “pushed the animal over the edge” |
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|
DKA signalment in cats
|
-Presents at a younger age
--presence of concurrent disease pushes pancreas into failure earlier -Abyssinians and Siamese are over-represented -Neutered males, and males in general -Overweight body condition but thinner due to crisis |
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|
Clinical signs of Dogs presenting with DKA
|
-PU/PD
-Lethargy -inappetence or anorexia -Vomiting -Weight loss |
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|
Clinicals signs of cats presenting with DKA
|
-Lethargy
-Inappetence -Weight loss -PU/PD -Vomiting -Diarrhea -Polyphagia |
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|
Physical exam of dog with DKA
|
-Overweight or underweight body condition
-Dehydration --most important, dangerous, and unspecific sign -Cranial organomegaly -Abdominal pain -Cardiac murmur -Mental dullness -Dermatologic abnormalities -Dyspnea, coughing, abnormal lung sounds -Cataracts |
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|
Physical exam of cat with DKA
|
-Dehydration (most important!)
-Neurologic abnormalities --dull mentation, obtunded, recumbent -Plantigrade stance -Underweight -Overweight -Obese |
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|
Diagnostic Evaluation of animals with DKA
|
-Complete diagnostic evalulation is recommended
-Need to find out what the other disease is that is causing DKA -CBC/Chem -Urinalysis -Electrolytes |
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|
CBC for animals with DKA
|
-Anemia in 50% of dogs
-Anemia is unrelated to hypophosphatemia -Left shift neutrophilia -Normal platelet count in most cats, thrombocytosis in 10% and thrombocytopenia in 17% |
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|
Chem screen for dogs with DKA
|
-97% of dogs have high ALP activity
--much higher than ALT and AST --produced in bile duct epithelium --due to increased stress and concurrent pancreatitis -50% have high cholesterol, hyperlipidemia |
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|
Chem screen for Cats with DKA
|
-54% have high ALT
-96% have high AST --from hepatocytes and muscle lysis --occurs with hepatic lipidosis -59% have high bilirubin -No steroid-induced ALP |
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|
Urinalysis in animals with DKA
|
-Glucose
-Ketones (acetoacetate) -Proteinuria -Sediment may not reveal infection, may need to do a culture |
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|
Electrolyte abnormalities with DKA
|
-Hypokalemia
-Hypophosphatemia -Hyponatremia -Hypomagnesia -At the end of the day, all are decreased -All are important, all can kill the patient! |
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|
Potassium and DKA
|
-Animal is in a state of acidosis, high concentration of H ions outside of the cell
-Push hydrogen ions into cell by trading with K ions -K ions go out and are excreted in urine, vomiting --can also bind to keto acids to form keto-salts -Insulin is anabolic, pushes electrolyte cofactors into the cells --shifts from extracellular fluid into cells very rapidly, dangerous! -happens acutely |
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|
Clinical significance of hypokalemia
|
-Muscle weakness
-Paralysis -Respiratory depression -Cardiac electrical conduction abnormalities |
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|
Hypokalemia in dogs with DKA
|
-Initially low in half of dogs
-Eventually low in most dogs |
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|
Hypokalemia in Cats with DKA
|
-Initially half are low
-Eventually most become low |
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|
Hypophosphatemia and DKA
|
-High concentration of H ions, neutralize by pushing negatively charged PO4 out of the cell
-Intracellular store of phosphate is destroyed -With animal on fluids, osmotic diuresis -Insulin therapy moves phosphate back into cell --dramatic shift from extracellular to intracellular space -No exchange, just pushed out because it is negatively charged |
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|
Clinical signs of Hypophosphatemia
|
-Weakness
-Respiratory depression -Hemolytic anemia -Cardiac dysfunction -Decreased 2,3-DPG and delivery of oxygen -Seizures in dogs |
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|
Hyponatremia and DKA
|
-High concentration of hydrogen ions outside of cell causes activation of Na/H exchanger to correct pH
--H is brought into cell, Na goes out -Na is flushed out with osmotic diuresis -Hyperlipidemia causes fictitious hyponatremia and interferes with measurement |
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|
Clinical significance of Hyponatremia
|
-Relative Intracellular hypernatremia if extracellular Na is depleted
--Water flow into cells to osmotically balance -Cerebral swelling and cell rupture -Altered mental status |
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|
Hypomagnesium and DKA
|
-Insufficient dietary intake of Mg
-Increased renal excretion of Mg -Increases risk of heart disease -Get hypokalemia, hyponatremia --exacerbates problems with other electrolytes -Insulin resistance 0Hypertension, hyperlipidemia, and increased platelet aggregation |
|
|
Magnesium in cats with DKA
|
-Total initial serum Mg concentration is positively correlated with creatinine concentration and ionized Mg concentration
-At risk for underlying renal disease --more likely to leak Mg? |
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|
Association between venous pH and discharge
|
-low pH leads to less likely to be discharged
-More acidotic patients are less likely to go home |
|
|
Outcome of Cats with DKA
|
-18% recurrence
-35% euthanized at median treatment -12% euthanized after second or third episode of DKA -3% died during initial 24 hours of treatment -Creatinine, BUN, and Mg represent renal function and indicate outcome in cats -Increased bilirubin concentration is associated with poor outcome |
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|
Treatment of DKA
|
-IV fluids
-Correction of electrolyte abnormalities -Correction of hyperglycemia (insulin) -Correction of acidosis -Address concurrent disease --if concurrent disease is not addressed, DKA will not go away |
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|
Fluid therapy for DKA
|
-IV fluid therapy is most important component of DKA therapy
--Dehydration can kill the animal! -Helps control electrolytes -Saline helps with Na --add K -Just giving fluids will bring down glucose levels -DO NOT give insulin right when patient arrives! Will cause glucose to drop too quickly |
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|
Correction of hypokalemia and DKA
|
-Add K to 250 ml bag
-Administer at a rate that is not greater than 0.5 mEq/kg/hour -Make sure Mg is normal and there are not other electrolyte abnormalities |
|
|
Correction of Hypophosphatemia in patients with DKA
|
-Give potassium phosphate
--Administration of K must also be taken into account! |
|
|
Correction of hyponatremia in DKA patients
|
-Give Na, saline diuresis
|
|
|
Correction of hypomagnesia in DKA patients
|
-Magnesium sulfate
|
|
|
Correction of hyperglycemia in patients with DKA
|
-Give fluids first
-After 6 hours, give insulin --only give IV or IM, not SQ --patients are too dehydrated, will not absorb anything from SQ -Give 2.2 units/kg/250ml bag of NaCl to both dogs and cats |
|
|
Time to resolution of DKA
|
-Regular insulin: 60 hours
-Lispro: 30 hours |
|
|
IM insulin Administration
|
-Administer regular crystalline insulin IM every hour
-Begin with 0.2 units/kg IM -Proceed with 0.1 units/kg 1 hour later -Continue with 0.05, 0.1 or 0.2 units/kg depending on how fast glucose has dropped --if glucose drops less, give more insulin -Can also Use glargine insulin given IM |
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|
Correction of Aicidosis in patients with DKA
|
-Give Sodium Bicarbonate at 0.3x body weight * base excess
-Bicarbonate administration Can contribute to worsening of cerebral edema --poor prognosis in humans --Only consider if pH stays below 7 for more than 1 hour |
|
|
Address concurrent diseases in patients with DKA
|
-Totally necessary!
-Treatment of concurrent diseases decreases secretion of diabetogenic hormones --results in decreased insulin resistance |
|
|
Prognosis for DKA
|
-70% of patients survived and were discharged
-Mean hospitalization time was 6 days -7% develop recurring episodes -Dogs with hyperadrenocorticism (cushing’s) are less likely to be discharged -Degree of acidosis is associated with outcome |
|
|
Hyperosmolar Non-ketotic diabetes mellitus
|
-Very very very rare, 1% of all diabetics
-Hyperosmolarity, greater than 325 -Severe hyperglycemia -No ketosis because there is some residual insulin action -Increased plasma osmolarity results in intracellular fluid moving to extracellular space -Rapid correction of hyperosmolarity is potentially painful |
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|
Insulinoma
|
-Pancreatic beta cell tumor
-Most common pancreatic tumor in dogs -Functional tumor, Secretes insulin without inhibition -Excess insulin results in hypoglycemia -In normal patients, insulin secretion is depressed when blood glucose is less than 60 mg/dl -In patients with insulinoma, high concentrations of insulin are secreted independently of blood glucose concentration |
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|
Excess insulin concentration
|
-Results in decreased blood glucose concentration
-Increased glucose uptake from the blood into the tissue -Decreased glucose is released from the liver into the blood --decreased gluconeogenesis and glycogenolysis, no glucose is released into the blood |
|
|
Effects of low blood glucose concentration
|
-Hypoxic damage to CNS
--first in cerebral cortex, then in metabolically slower areas -PNS degeneration and demyelination can occur -Release of diabetogenic hormones --glucocorticoids, glucagon, growth hormone, catecholamines |
|
|
Insulinoma signalment
|
-Develops in older patients
-Mostly a dog disease --rare in cats, may have increased frequency of insulinoma -Can effect many breeds -No sex predilection |
|
|
History of Insulinoma
|
-Initial signs can be mild, usually present for 6 months-1 year before owner does anything
-Critical signs may be episodic --release of diabetogenic hormones temporarily resolves hypoglycemia -Clinical signs are worsened by fasting, excitement, exercise, and eating --Eating stimulates insulin secretion that results in post-prandial hypoglycemia |
|
|
Hypoglycemia clinical signs
|
-Lethargy
-Weakness -Ataxia -Collapse -Abnormal behavior or mentation -Seizures -Coma |
|
|
Clinical signs due to release of diabetogenic hormones
|
-Tremors, muscle fasciculations
-Nervousness, restlessness -Polyphagia -PU/PD |
|
|
Effects of Hyerinsulinemia on protein and fat
|
-Decreases mobilization of amino acids from muscle
-Decreases lipid mobilization from adipose tissue -Decreases catabolic effects |
|
|
Physical exam for Insulinoma
|
-Usually unremarkable
-Possible weight gain due to anabolic effect of insulin or athletic appearance -Possible peripheral neuropathy |
|
|
Diagnostic work-up for insulinoma
|
-CBC
-Chem screen -Urinalysis -Ultrasound -Insulin concentration |
|
|
Abdominal Ultrasound for Insulinoma
|
-Does not usually identify a pancreatic miss
-If it does, is very helpful! |
|
|
Definitive diagnosis for Insulinoma
|
-High insulin concentration and low blood glucose
-Need to wait until blood glucose has gone down before measuring blood glucose |
|
|
Treatment options for Insulinoma
|
-IV dextrose administration in acute stage
-Surgical excision is optimal but difficult --most likely has metastasized -Feed complex carbohydrates via canned or dry food --feed frequently -Avoid moist, soft foods -Prednisone: catabolizes glycogen to carbohydrates -Diazoxide -Somatostatin -Streptozocin |
|
|
Diazoxide as treatment for insulinoma
|
-Treatment for insulinoma
-Activates ATP-sensitive K channels, opens channels --decreases cell membrane potential, Ca channels do not open -Inhibitis insulin secretion by decreasing intracellular Ca -Stimulates hepatic gluconeogenesis and glycogenolysis -Inhibits tissue uptake of glucose |
|
|
Prednisone as treatment for insulinoma
|
-Increases gluconeogenesis
-Decreases peripheral glucose uptake |
|
|
Somatostatin as treatment for Insulinoma
|
-Inhibits synthesis and secretion of insulin from normal and neoplastic beta cells
|
|
|
Streptozocin
|
-Nitrosurea antibiotic
-Derived from Streptomyces acromogenes -Destroys beta cells in pancreas and metastatic lesions --selectively affects beta cells in all mammalian cell cycle stages -Alkylating agent -Not myelosuppressive -Used in humans with metastatic beta cell carcinoma |
|
|
Insulinoma Prognosis
|
-Poor
-Mean survival time is 1 year from onset of clinical signs -Only chance for a cure is surgery |
|
|
Rare Endocrine Pancreatic Diseases
|
-Glucagonoma
-Gastrinoma -Pancreatic polypeptidoma |
|
|
Glucagonoma
|
-Pancreatic alpha cell tumor
-Rare in the dog -Not yet reported in the cat |
|
|
Pathophysiology of Glucagonoma
|
-Excess glucagon results in insulin resistance and diabetes mellitus
-Extremely catabolic -profound deficiency in amino acids results in dermatologic issues --necrolytic migratory eruthema in humans |
|
|
Necrolytic Migratory Erythema
|
-AKA superficial necrolytic dermatitis, metabolic epidermal necrosis
-Seen in association with severe liver disease and diabetes mellitus --in humans associated with glucagonoma -Severe hyperkeratosis -Skin erosions, ulcerations, alopecia, exudation, thick adherent crusts around mucocutaneous junctions, ears, and pressure points -Secondary skin infections are common |
|
|
Clinical signs of Glucagonoma
|
-Necrolytic migratory erythema
-Diabetes mellitus -Small intestinal diarrhea |
|
|
Diagnosis of Glucagonoma
|
-Necrolytic migratory erythema
-Diabetes mellitus -Hyperglucagonemia -presence of a pancreatic tumor containing glucagon --biopsy pancreas |
|
|
Diagnosis of Hepato-cutaneous Syndrome vs. glucagonoma
|
-Necrolytic migratory erythema
-Diabetes mellitus -Severe liver disease -No hyperglucagonemia -No pancreatic tumor |
|
|
Treatment for Glucagonoma
|
-Surgical excision
-Somatostatin -Treat skin diseases with IV administration of amino acids -Oral supplementation of amino acids via egg yolks -Treat secondary infections |
|
|
Prognosis for glucagonoma
|
-poor
-Quality of life is not good |
|
|
Gastrinoma
|
-Pancreatic tumor
-Arises from residual fetal delta cells or delta cells that revert back to fetal function and secrete gastrin -normal adult pancreas does not secrete gastrin -Gastric secretion results in increased gastric acid (HCl) secretion --causes GI ulceration, vomiting, diarrhea, anorexia, weight loss, lethargy, depression |
|
|
Clinical sigs of Gastrinoma
|
-Vomiting, sometimes with blood
-Diarrhea, hematochezia, melena -Weight loss -Anorexia -Abdominal pain -PU -Lethargy, depression -Regurgitation |
|
|
Gastrinoma PE
|
-Usually unremarkable
-Animal will be vomiting -May see dehydration, abdominal pain, tachycardia, fever -palpable abdominal pancreatic mass sometimes |
|
|
Diagnosis of Gastrinoma
|
-Hypergastrinemia, high gastrin concentration
-Secretin or calcium stimulation test -Pancreatic mass that contains gastrin |
|
|
Gastrinoma treatment
|
-Surgical resection!
-Somatostatin -Cometidine, ranitidine, omeprazole to reduce gastric acid secretion -Sucralfate or misoprostol to treat GI ulceration |
|
|
Gastrinoma prognosis
|
-Poor |
|
|
Pancreatic polypeptoma
|
-reported in one dog |
|
|
Adrenal Anatomy
|
-Craniomedial to the kidneys
-Weigh about 1 gram in adult dog -Left adrenal is slightly larger and more caudal -Composed of medulla and cortex -Big important blood vessels travel across adrenal surface |
|
|
Layers of the Adrenal Cortex
|
-Zona glumerulosa
-Zona fasciculate -Zona reticularis |
|
|
Adrenal Medulla function
|
-Not essential for life
-Secretes catecholamines in response to stress and sympathetic stimulation -“Fight or flight” response -Epi -Norepi -Dopamine |
|
|
Adrenal cortex function
|
-Essential for life
-Secretes steroids -Corticosterone is secreted from all 3 layers -Cortisol is secreted from fasciculata and reticularis -Sex hormones from Fasiculata and reticularis -Mineralocorticoid from glomerulosa |
|
|
Synthesis of Catecholamines
|
-Tyrosine is converted into Dopa (dihydroxyphenalanine)
-Dopa is converted to dopamine, then to norepi, then epi -Norepi has negative feedback inhibition on tyrosine hydroxylase, decreases catecholamine production |
|
|
Catabolism of Catecholamines
|
-Metabolized and secreted as Vanillylmandelic acid (VMA), normetanephrine, and metanephrine
-Half-life of catecholamines is very short --hard to measure --Easier to measure metabolites |
|
|
Steroid Synthesis
|
-All are made from cholesterol
-Cholesterol is converted to pregnenolone via ACTH stimulation -Same enzyme is used many times in pathway --can inhibit one enzyme, will inhibit rest of the pathways -Many enzymes are p450 enzymes -Formation of steroids in layers depends on presence of enzymes in the layer --if enzyme is not present, hormone will not be made in that layer |
|
|
Corticoids
|
-Have both glucocorticoid and mineralocorticoid activity
|
|
|
Affects of ACTH on steroid synthesis
|
-Increase conversion of cholesteryl esters to free cholesterol and prengenolone
-Increases synthesis and p450 enzymes |
|
|
Affects of Angiotensin II on steroid synthesis
|
-Increases conversion of cholesterol to pregnenolone
-Increases aldosterone synthase activity |
|
|
Actions of Catecholamines
|
-Epi and NorEpi
-Stimulate alpha and beta adrenergic receptors -Mimic effects of adrenergic nervous system --increase HR< excitability, force contractility of heart --decrease peripheral resistance --increase alertness -increase metabolic rate -Increase glycogenolysis and lipolysis |
|
|
Actions of Dopamine
|
-Mostly unknon
-Causes renal vasodilation and vasoconstriction elsewhere -Increases systolic blood pressure -increases force of cardiac contraction -increases natiuresis |
|
|
Actions of Glucocorticoids
|
-Sustain life!
-Bind intracellular receptors, promote DNA transcription and leads to enzyme synthesis that changes cell function -Permissive effect on catecholamines, glucagon, and EPO -Physiologic effects are different than pharmacologic and pathologic effects |
|
|
Specific Actions of Glucocorticoids
|
-Increase protein catabolism
-increase hepatic uptake of amino acids -Increase gluconeogenesis -Increase formation of active form of glycogen synthase -Increase glucose 6-phosphatase activity --results in increased blood glucose concentration -Decreases peripheral glucose utilization -has anti-insulin effect, except in brain and heart -Decrease hepatic lipogenesis -increase plasma free fatty acids -Causes hyperlipidemia and ketosis in diabetics -Inhibits ACTH secretion -Promotes vascular smooth muscle reactivity -Increases GFR -Increases number of circulating neutrophils, monocytes, platelets and RBCs -Decreases number of circulating lymphocytes, eosinophils, and basophils -Resists stress |
|
|
Actions of Mineralocorticoids
|
-Bind intracellular receptors, promote DNA transcription
--leads to synthesis of Na and K channels and pumps --changes Na and K absorption and secretion in the kidney -Increase Na resorption from urine, sweat, saliva, gastric juices -Promote secretion of H and K |
|
|
Regulation of Catecholamine secretion
|
-Decreases during sleep
-increases in emergency situations --hypoglycemia, hypothermia -NorEpi inhibits tyrosine hydroxylase if too much catecholamines are produced |
|
|
Regulation of Glucocorticoid Secretion
|
-CRH is secreted from hypothalamus
--stimulates secretion of ACTH from anterior pituitary --CRH does not have effect on intermediate pituitary -ACTH stimulates adrenal cortex to synthesize cortisol -Cortisol negative feedback inhibits ACTH from anterior pituitary and CRH from hypothalamus |
|
|
Regulation of Mineralocorticoid Secretion
|
-Aldosterone is secreted from cortex zona glomerulosa
--causes decreased Na excretion, increased Na retention --Water follows Na, increases extracellular fluid volume --increases BP -Increased BP inhibits conversion of angiotensinogen to angiotensin I via renin --Less angiotensin I converting to Angiotensin II, less angiotensin II to stimulate aldosterone secretion -ACTH can bind to adrenal cortex and stimulate aldosterone secretion to a small extent |
|
|
Adrenal Diseases
|
-Hyperadrenocorticism
-Primary hyperaldosteronim -Hypoadrenocorticism -Pheochromocytoma (adrenal medulla) |
|
|
Hyperadrenocorticism (Cushing’s disease)
|
-Common disease in dogs
-not common in cats -Pituitary dependent hyperadrenocorticism -Adrenal tumor -Iatrogenic -All cause the exact same clinical signs! --hard to know origin of issue -Treatment modalities are different |
|
|
Pathophysiology of PDH
|
-Likely due to a primary defect in the pituitary and not in the hypothalamus
-Chronic excess secrethion of ACTH -90% are pituitary tumors --70% in anterior lobe, pars distalis --30% from intermediate lobe, pars intermedia -Pharmacological intervention is different for the different lobes --Anterior lobe, CRH and glucocorticoid negative feedback --intermediate lobe, dopamine inhibits ACTH secretion |
|
|
Pathophysiology of Adrenal Tumors
|
-Adrenal adenomas or carcinomas
-Secrete excess glucocorticoids, suppress CRH and ACTH --go to pituitary and hypothalamus -Less ACTH secretion, contralateral adrenal atrophies -Also get atrophy of zona reticularis and zona fasciculate in adrenal with tumor -Histological classification can be challenging |
|
|
PDH
|
-80-85% of dogs with hyperadrenocorticism have PDH
-90% is pituitary adenoma --70% anterior lobe adenoma --30% intermediate lobe adenoma -85-90% of pituitary adenomas are microadenomas, less than 1cm in diameter -10-15% of pituitary adenomas are macroadenomas, more than 1cm in diameter -Small % of dogs have pituitary hyperplasia or carcinoma instead of adenoma -Anterior lobe pituitary microadenoma is most common |
|
|
Incidence of Adrenal tumor Types
|
-50% adenomas
-50% carcinomas |
|
|
Signalment for Cushing’s disease
|
-Older dogs, 10-11 years old
-Females may be slightly higher risk -Smaller breeds develop PDH -Larger dogs develop adrenal tumors |
|
|
Clinical signs of Cushing’s Disease
|
-Look exactly the same regardless of the “type” of cushing’s
-PU/PD --most profound --too much glucocorticoids, bind ADH receptors and prevent ADH binding -Polyphagia --Glucocorticoids are catabolic, breaking down energy stores -Abdominal enlargement -Truncal obesity -Muscle weakness, lethargy, possible lameness --breakdown of connective tissue, predisposes to ligament and tendon tears -Panting -Testicular atrophy or failure to cycle --glucocorticoids suppress LH and FAH secretion -Myotonia |
|
|
Abdominal enlargement with Cushing’s disease
|
-Liver enlargement due to glycogen accumulation in the liver
-Swollen hepatocytes -Muscle and skin is broken down so liver “hangs out” -Fat is re-distributed from limbs to trunk |
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Panting and Cushing’s
|
-Truncal obesity prevents chest expansion
-Breakdown of intercostal muscles make chest expansion difficult -Pneumonia due to immune suppression from glucocorticoids -Acute thromboembolic disease |
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Thromboembolic Disease and Cushing’s
|
-Too little trypsin
-Too much tissue plasminogen inhibitor -Too little tissue plasminogen activator -Decrease conversion of frbrin to fibrin-split products -Dogs with cushing’s are hypocoagulytic, cannot break down clots --“hypercoagulable” is not totally correct --form clots normally but cannot break down clots |
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Skin issues associated with Cushing’s disease
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-Alopecia
-Shaved hair will not regrow -Thin skin (look in inguinal area) --may see vasculature under skin -Poyderma -Bruising (more common in cats) -Dehiscence of healing lesion -Calcinosis cutis, deposition of Ca in the skin -Recurrent infections due to immunosuppression |
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Immunosuppression due to glucocorticoids
|
-Lympholytic, fewer circulating antibodies
-Decrease expression of Fc receptors on macrophages --no ability to bind antibodies -Decrease chemotaxis of neutrophils and ability to adhere -Causes recurrent infections, skin infections, and pneumonia |
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Physical Exam findings of Cushing’s Patient
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-Abdominal enlargement
-Hepatomegaly -Truncal obesity -Muscle weakness and muscle wasting -Lethargy and possible lameness -Panting -Alopecia -Hyperpigmentation -Failure to regrow shaved hair -Thin skin -Pyoderma -Exophthalmos, breakdown of musculature and connective tissue around the eye -Sudden Acute Retinal Degeneration (SARDS) |
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Hyperpigmentation and Cushing’s disease
|
-Melanin-stimulating hormone is produced from same peptide as ACTH
-Increased synthesis fo ACTH results in increased synthesis of MSH --causes hyperpigmentation |
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Concurrent conditions that can affect clinical signs of a Cushing’s patient
|
-UTIs
-Cystic calculi, excess secretion of Ca in urine -Glomerular disease -Dermatitis or pyoderma -Pneumonia -Other infections -Diabetes mellitus -Acute pancreatitis -Hypertension and CHF --excess ACTH causes excess secretion of alosterone -Pulmonary thromboembolism -Sepsis -CNS signs due to a macroadenoma (rare)acting as space-occupying lesion |
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Conditions associated with high cholesterol concentration
|
-Hyperthyroid
-Diabetes mellitus -Cushing’s disease -Causes increased risk for acute pancreatitis? |
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Diagnosing Hyperadrenocorticism (Cushing’s)
|
-History and Clinical signs
--MUST have classic history and clinical signs for diagnosis! --tests are imperfect, give false positives and false negatives -Physical exam findings -Clinicopathologic findings consistent with a diagnosis -Adrenal axis testing --only do tests if you are sure that the dog has cushing’s and you want to treat! |
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Initial diagnostic evaluation of Cushing’s
|
-CBC
-Chem screen -Urinalysis -Urine culture -Abdominal ultrasound |
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CBC for Cushing’s
|
-Can be normal
-Can have high hematocrit or normal --Glucocorticoids induce EPO, makes more RBCs -Can have thrombocytosis -WBC “stress leukogram” may be present -Neutrophilia with a left shift if there is an infection |
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Chem screen for Cushing’s
|
-High ALP due to excess steroid secretion
-high ALT and high AST --due to glycogen accumulation in hepatocytes -Lipema may be present -Hypercholesteroemia may be present -Hyperglycemia -Mild hypopohsophatemia -Looks like Diabetes mellutis chem screen --treat diabetes first and hope it resolves --if no resolution, test for cushing’s |
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Urinalysis for Cushing’s
|
-Hyposthenuria, dilute urine
-Pyuria -Glucosuria |
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Urine culture and sensitivity for Cushing’s
|
-Should always be performed in dogs suspected of cushing’s even if WBCs are not present in urine sediment
-Dilute urine can mask presence of WBCs |
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Abdominal Ultraound for Cushing’s
|
-Can be helpful but does NOT diagnose cushing’s
-gives shape of the adrenals -Does not tell anything about secretion of hormones or lack thereof -Adrenals may be bilaterally plump with pituitary adenoma -Adrenal tumor will have one large and one atrophied tumor -adrenal mass and adrenal atrophy -Diffusely enlarged, hyperechoic liver -Metastasis -concurrent disorders (cystic calculi) |
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Adrenal Mass
|
-Can invade caudal vena cava
-Look for metastasis to liver |
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Abdominal and thoracic radiographs for Cushing’s
|
-Hepatomegaly
-Good abdominal detail due to excess fat deposits -Calcinosis cutis -Ectopic calcification of the airways -Adrenal mass Radiographic findings are nonspecific, do not confirm a diagnosis |
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Confirming Cushing’s
|
-Adrenal axis testing
-Only in animals with clinical signs and clinicopathologic findings that indicate hyperadrenocorticism -Only done in dogs that you want to treat -Screening tests and differentiating tests |
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Screening test vs. differentiating test for Cushing’s
|
-Screening tests: indicates if the dog has Cushing’s
-Differentiating test: indicates what type of cushing’s --only done if the screening test has confirmed cushing’s disease |
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Screening tests for Cushing’s
|
-Does the dog have cushing’s?
-ACTH stimulation test -Low dose dexamethasone suppression test -Urine cortisol to creatinine ratio -Oral low dose dexamethasone suppression test (still in progress) |
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ACTH stimulation test
|
-Stimulates cortisol production
-Do when there are concurrent diseases -Fast, 1 hour test -Normal: --pre-ACTH cortisol should be 0.5-6 ug/dl --post ACTH cortisol should be less than 17 -PDH: --pre-ACTH cortisol should be 0.5-6 --post ACTH cortisol should be more than 22, really high, more ability to make cortisol due to hypertrophy -Adrenal tumor: --post-ACTH cortisol should increase beyond what is expected to be normal, maintains some capacity to respond |
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Low-dose dexamethasone suppression test
|
-Suppresses cortisol production, dexamethasone acts like cortisol
-Do in dogs that are pretty stable, have PU/PD and polyphagia and no concurrent disorders -8 hour test, longer test where animal needs to be left alone -Normal: cortisol secretion should be suppressed, less than 1 at 4 and 8 hours after injection -Adrenal Tumor: secretes glucocorticoids autonomously, un-regulated --dexamethasone will not suppress cortisol levels, stays above 1.4 -Pituitary adenoma: autonomously secreting ACTH --dexamethasone will not suppress cortisol levels, stays above 1.4 |
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Urine Cortisol Creatinine Ratio
|
-Developed because measurement fo a single cortisol level in blood is unreliable
-Looks at cortisol in the urine, reflects cortisol in blood over past few hours -Will have elevated urine cortisol: creatinine ratio -Test is non-specific, cannot differentiate stress from hyperadrenocorticism -Used to tell if dog does NOT have cushing’s -If low or normal, can definitively say the animal does not have cushing’s |
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Sensitivity and specificity of Cushing’s screening tests
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-ACTH stimulation test: specific
--if positive, know it really is positive --possible that some positive patients are missed -Low-dose dex test: sensitive --will pick up cushing’s, but get false positives --most common reason for false positives is stress (concurrent disorder or general stress) -Urine cortisol:creatinine ratio: sensitive |
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Differentiating Tests for Cushing’s
|
-Do to figure out what type of cushing’s the dog has
-LDDS test -Endogenous ACTH concentration -High dose dexamethasone suppression test |
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Low dose dexamethasone suppression test
|
-Screening test AND differentiating test
-4 hour serum cortisol concentration should be less than 1.4 or less than 50% of baseline -If cortisol stays high, cannot differentiate Pituitary adenoma from adrenal tumor -40% of dogs with PDH have no suppression -Sometimes get transient suppression of microadenoma in pituitary --will stop secreting ACTH --4 hours: suppression --8 hours, goes back up -Adrenal tumors DO NOT suppress |
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Endogenous ACTH concentration differentiation test for Cushing’s
|
-One measurement, likely to give yes/no answer
-Pituitary tumor: ACTH will be high (above 45) -Adrenal tumor: ACTH will be low (below 10 -Gray zone between 45 and 10 -Blood draw goes into purple top, then removed from EDTA and placed in a plastic tube --will adhere to glass, concentration goes down incorrectly |
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High Dose dexamethasone suppression test for differentiating Cushing’s
|
-8 hour test
-Give high dose of dexamethasone, want to suppress pituitary dependent ACTH production -Will not suppress adrenal tumor -Still have significant number of dogs with pituitary tumor that will not suppress -Not the best test, does not always work |
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Tests for Cushing’s that cannot be used to differentiate
|
-Abdominal ultrasound
-CT -MRI -Supportive, but not diagnostic of disease |
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Diagnosis of Iatrogenic Hyperadrenocorticism
|
-History and clinical signs
--animal is on exogenous steroids -Serum cortisol is expected to remain low after ACTH stimulation -Differentiating test is not needed |
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Treatment of Cushing’s Disease
|
-Treatment is a big deal! Can kill the patient!
-medical treatment is most common -Lysodren -Trilostane -Deprenyl -Surgery -Stereotactic radiation therapy -Ketoconazole -Photon irradiation |
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Lysodren
|
-Mitotane, Bristol-Myers Squibb
-Causes severe necrosis of zona fasciculate and zona reticularis, some necrosis of zona glomerulosa -NOT FDA approved for dogs -Only 500mg tab, inconvenient -Induction phase and maintenance phase -Need constant monitoring and adjustment of dose --taper dose to each dog individually |
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Lysodren induction phase
|
-Goal is to destroy the adrenals, destroy cortisol secreting layers
-25-50 mg/kg for 7 consecutive days, give daily --on last day do ACTH stimulation, if still high continue with induction phase -May give prednisone also to prevent crisis -Need to be careful to not give too much and kill adrenals completely |
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Lysodren Maintenance phase
|
-Retains destruction of cortisol secreting layers of the adrenal glands
-25-50 mg/kg per week, divided into 2 weekly doses --daily dose becomes weekly dose |
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Key things about Lysodren therapy
|
-Excess lysodren can cause death! Do not give too much
-Monitor patient really well! -Constant and excellent communication between vet and owner are essential -Perfect dose is achieved by trial and error, practice -Perfect dose changes over time |
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Monitoring Lysodren treatment by owner
|
-Decreased appetite
-Vomiting -Decreaed water consumption -Lethargy, weakness, ataxia -Diarrhea |
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Monitoring of Lysodren treatment by veterinarian
|
-Clinical monitoring
-ACTH stimulation test if: --lysodren overdose is suspected --lysodren underdose is suspected -End of every induction phase -Before changing lysodren dose -If complications occur (UTI or other infection) -every 3-4 months when dog appears well-regulated |
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Results of ACTH stimulation test in Lysodren treated dogs
|
-Post- ACTH stimulation cortisol concentration should be less than 5ug/dL
--at VHUP, should be 2 -Not supported by studies! |
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Lysodren Overdose
|
-Common!
-Varies in severity -Confirm with ACTH stimulation test -May not need treatment, may need treatment with IV fluids, dex, correction of elextrolyte disturbances |
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Trilostane
|
-Treatment for Cushing’s
-Synthetic steroid analogue -can bind enzymes that normally bind cortisol -Specifically binds 3 beta hydroxysteroid dehydrogenase inhibitor -Blocks many hormone pathways --blocks production of cortisol and aldosterone -FDA approved -Can cause adrenal necrosis via unknown pathology --occurs in first 4 weeks of treatment |
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Trilostane and Potassium
|
-Trilostane treatment results in increased serum potassium concentration
-Unknown cause --causes cell nerosis, which causes release of intracellular K? --aldosterone concentration is decreased? -In addisonian crisis, will see increased K --if dog is happy and not sick, not addisonian crisis --if dog is sick, may be addisonian crisis |
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Aldosterone and Trilostane
|
-Aldosterone and Cortisol are not equally affected by trilostane
-Preferentially decreases cortisol and not aldosterone |
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Alopecia X and Trilostane
|
-Helpful for treating alopecia X condition
-May be due to increased 17-hydroxyprogesterone, trilostane decreases 17-OHP concentration -Not cushinoid dogs, and do not become addisonian --Dogs that do not have Cushing’s are less sensitive to drugs -Breed related --Alaskan Malamute --Chow chow --keeshond --pomeranian --Samoyed --Siberian husky |
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Trilostane and Adrenal gland size
|
-Adrenal gland will be enlarged after treatment with trilostane
-Less glucocorticoids produced, less glucocorticoid inhibition of ACTH --causes enlargement of pituitary -Diffuse and quietly enlarged, not necrotic |
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Survival of Cushinoid patients with Treatment
|
-Do well, drugs work well
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Trilostane formulation
|
-10, 30, 60 mg capsules
-Also 5 mg capsules by compounding pharmacies --watch out for variability! -Dose twice daily, 1-3mg/kg orally divided into 2 doses -Dose can be increased up to 40-50mg/kg/day if needed --Increase gradually within first few months of treatment -May need to discontinue medication as hypoadrenocorticism develops -Monitor based on stimulation tests --test on days 10-14, 30, and 60, then every 3-4 months |
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When to do an ACTH stimulation test?
|
-Standard: 4-6 hours after trilostane administration
--time of peak action of enzyme -Can also do stimulation tests 10-12 hours after administration -Always interpret in light of the clinical signs |
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Commonside effects of Trilostane
|
-Lethargy
-Anorexia -Hyperkalemia -Hyponatremia -Addisonian crisis -Uncommon: --adrenal necrosis --irreversible hypoadrenocorticism --death |
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Trilostane vs. Lysodren
|
-Same cost
-FDA approved vs. non FDA approved -Reversible action sometimes -Safer? |
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L-Deprenyl / Selegiline / Anipryl
|
-Irreversible monoamine oxidase inhibitor type B
-MAOb normally degrades dopamine -Inhibition causes increased dopamine concentration --High dopamine inhibits ACTH secretion from intermediate pituitary -Only 30% of dogs have pars intermedia tumor --beneficial for about 20% of dogs with Cushing’s -Only FDA approved drug approved for treatment of hyperadrenocorticism -Approved for cognitive dysfunction in dogs -Used in addition to trilostane or lysodren |
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Surgery for treatment of Cushing’s
|
-Remove pituitary
-All hormones from pituitary are gone! -Need to supplement animal with prednisone, thyroid hormone, -Surgery is complicated, requires special training --need a surgeon who can do it! Need to be really really good for success -May be curative for adenoma, need to supplement with small amounts of mineralocorticoids and glucocorticoids for a few months --contralateral adrenal will be shrunken, will grow back but takes time -Higher success if intervened early |
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Stereotactic Radiation Therapy for Adrenal Tumor Cushing’s
|
-Highly focused dose of radiation to the tumor
-3 fractions of treatment -less radiation to surrounding tissue -Successful in alleviating clinical signs of adenoma |
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Lysodren Treatment for Cushing’s caused by adrenal tumors
|
-When surgery is not recommended due to metastasis
-Larger doses than for PDH -Truly destroys the adrenal glands and possible metastasis |
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Trilostane for Adrenal tumors
|
-Will inhibit glucocorticoid synthesis but won’t do anything for the actual tumor
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Not recommended treatments for adrenal tumors
|
-Ketoconazole
-Proton irradiation |
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Atypical Cushing’s
|
-Dog that presents with PU/PD, polyphagia, big liver, thin skin, collapsing trachea
-CBC looks like cushing’s -Liver has glycogen accumulation -All adrenal testing is negative, cannot confirm cushing’s disease -Something else is binding the steroid and causing clinical signs? --do not know what it is -Treat with Lysodren, do not know what intermediary is causing issue --Trilostane will cut off some hormones and increase synthesis of others |
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Feline Hyperadrenocorticism
|
-Rare
-over 90% of cushinoid cats are diabetic -Thin skin results in skin tears, skin is paper-thin -No steroid induced ALP, no elevated ALP -Protocols for ACTH stimulation test, LDDS tests, and HDDS tests are different -Different treatment: surgery and metyrapone (11-beta-hydroxylase inhibitor) --no response to lysodren |
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Metyrapone
|
-11-beta-hydroxylase inhibitor
-Treatment for feline cushing’s |
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Spontaneous skin tears in cats
|
-Diabetic cat with cushing’s
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Treatment of cats with Cushing’s
|
-Surgery!
-Hard to give cats mediations and meds are not that effective --tastes bad, cats are grouchy -Cats handle surgery better than dogs -Retroperitoneal approach |
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Prognosis for cats with Cushing’s
|
-Variable
-Better with pituitary microadenomas than with adrenal carcinoma |
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Primary Hyperaldosteronism
|
-Rare, more common than cushing’s
-Mostly in cats -Usually due to unilateral adrenal adenoma or carcinoma, bilateral adrenal hyperplasia -Excess aldosterone secretion causes increased Na retention --leads to increased extracellular plasma volumes, hypertension, and hypokalemia -Will see elevated serum aldosterone concentration -Clinical signs will be due to hypokalemia -Surgical treatment, remove! |
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Hypoadrenocorticism Addison’s Disease
|
-Common in dogs, rare in cats
-Primary: adrenocortical failure, failure of adrenal glands --more common -Secondary: failure of the pituitary or hypothalamus |
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|
Primary Adrenocortical Failure
|
-Failure of the adrenal glands
-Occurs when more than 90% of adrenocortical cells are lost --only need a small amount of cortex to be viable to mask clinical signs -Characterized by a decreased glucocorticoid and mineralocorticoid secretion |
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Causes of Primary Addision’s
|
-Immune-mediated destruction of adrenal glands
-Genetic component --poodles, portugese water dogs, labs -Granulomatous disease -Trauma -Iatrogenic from lysodren treatment |
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Secondary adrenocortical failure
|
-Rare
-Due to failure of pituitary or hypothalamus -Characterized by decreased glucocorticoid secretion --mineralocorticoid secretion will be normal |
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|
Causes of Secondary Addison’s
|
-Neoplasia
-Inflammation -Trauma -Brain disease -Iatrogenic due to abrupt discontinuation of chronic prednisone treatment |
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|
Lack of Aldosterone
|
-Hyponatremia, Na is excreted in urine
--no aldosterone to retain Na -Hypochloremia (Na and Cl travel together) -Reduced extracellular volume --VERY dehydrated patient -Dilute urine despite dehydration -Hyperkalemia -Acidosis |
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|
Lack of glucocorticoids causes…
|
-Anorexia
-Vomiting -Abdominal pain -Weight loss -Fasting hypoglycemia, glucocorticoids are not metabolizing glucose stores to glycogen -Lethargy due to hypoglycemia -Impaired tolerance to stress |
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|
Signalment of Addison’s disease
|
-Young to middle aged dogs, 5 years old
-70% of affected dogs are female -Poodles, Portuguese water dogs, and labs may be predisposed |
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|
Clinical signs of Addison’s disease
|
-Can be very mild
-Anorexia, weight loss or underweight body condition -Vomiting, diarrhea -Lethargy, weakness, PU/PD -Painful abdomen -Shaking/shivering due to hypoglycemia -Collapse |
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|
Physical exam of patient with Addison’s
|
-Depression
-Underweight -Weakness -Dehydration can be mild or severe -Bradycardia due to hyperkalemia -Weak pulses -Melena/hematochezia -Abdominal pain -Collapse |
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|
Bradycardia due to hyperkalemia
|
-K stays in the cell
-Increased K increases resting membrane potential |
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|
Diagnosis of Hypoadrenocorticism (Addison’s)
|
-History and clinical signs
--depression, weakness, vomiting --hypotensive -Physical exam findings -Clinicopathologic findings -Adrenal axis testing --ACTH stimulation test is only test that proves presence or absence of Addison’s disease |
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|
Addison’s disease and hypotension
|
-Aldosterone is not produced
-No retention of Na and water -No water in vasculature, hypotension |
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|
Initial Diagnostic evalulation for Hypoadrenocorticism
|
-CBC
-Chem -Urinalysis -Urine culture -Fecal parasitic examination -Fecal culture -Abdominal radiographs |
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|
CBC for dog with Addison’s Disease
|
-CBC may be normal
-RBC: hematocrit is low, but may be normal or high -WBC count is normally lower, but may be increased -Eosinophils and lymphocytes may be observed |
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|
WBCs and Addison’s disease
|
-Steroids induce stress leukogram:
--neutrophilia, Monocytosis, lymphopenia, eosinopenia -Without steroids, get reverse --body does not mount appropriate stress response that we would get from a dog that has glucocorticoids --lymphocytosis within the reference interval |
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|
Chem screen for dogs with Addison’s disease
|
-Na/K ratio is particularly important
--without aldosterone Na decreases and K increases -Azotemia -Hyponatremia -Hyperkalemia -Hypochloremia -Mild metabolic acidosis -Hypercalcemia -Hypoglycemia -Hypoalbuminemina -Hypocholesterolemia |
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|
Na/K ratio in Addison’s
|
-Should be assessed together
-More than 27 Na:K in normal dogs -Less than 27 Na:K in dogs with hypoadrenocorticism -Should do a stimulation test on all dogs with a Na:K ratio of 30 or less -Look at Na:K ratio in conjunction with lymphocyte count |
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Lymphocyte count and Addison’s
|
-Look at all dogs above 1.2 as potentially having Addison’s
-Dogs above 2.4 indicates very likely that the dog has addison’s disease -Look at lymphocyte in conjunction with Na:K ratio |
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|
Urinalysis and Addison’s Disease
|
-Urine is dilute in the face of dehydration
-Looks like kidney or liver disease -Do a urine culture due to PU/PD --do not expect to see bacteria, no growth expected |
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|
Fecal exam for Addison’s disease
|
-Always do fecal parasitic exam and fecal culture in dogs with vomiting and diarrhea
-Normal results are expected with Addison’s disease --negative for parasites and infection |
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|
Abdominal radiographs in Addison’s disease
|
-Always performed in dogs that are vomiting
--foreign body potential -Should be normal in dogs with Addison’s disease -May see microcardia secondary to dehydration -May see megaesophagus secondary to immune-mediated destruction of esophagus |
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|
Abdominal ultrasound with Addison’s disease
|
-Adrenals will be shrunken
|
|
|
ECG for Addison’s patients
|
-Prolonged P-R interval
-Short or absent P waves -Wide and short QRS complexes -Possible ventricular fibrillation -Consistent with hyperkalemia |
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|
DDx for PU/PD in younger dogs
|
-Kidney or liver disease
-Addison’s -Everything else is also possible |
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|
DDx for Eosinophilia
|
-Parasitism (MAIN differential!!!)
-Non-parasitic skin disease -Mast cell tumor -Addison’s/hypoadrenocorticism -Eosinophilic myositis, pneumonitis, enterocolitis -Hypereosinophilic syndrome -Eosinophilic leukemia -Eosinophilic granuloma complex |
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|
Pseudo Addison’s Disease
|
-Eosinophilia
-Vomiting and diarrhea -Low Na:K ratio -Looks like an addison’s patient -Can be caused by ANY severe GI disease --treat any possible underlying conditions before testing for Addison’s disease |
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|
DDx for Hyperkalemia and Hyponatremia
|
-Any severe GI disease
-Hypoadrenocorticism/Addison’s -Acute renal failure -Severe liver disease -Urethral obstruction -Uroperitoneum -Osmotic or diuretic induced diuresis -Acidosis due to DKA -Pleural effusion -CHF -Massive tissue destruction -Polydipsia -Artifact |
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|
DDx for Hypoglycemia
|
-Insulinoma
-Liver disease -Toy breed -Young animal -Hypoadrenocorticism -Sepsis -Neoplasia -Starvation -Severe malabsorption or maldigestion -Severe polycythemia -Growth hormone deficiency -Artifact |
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|
Hypoglycemia and Addison’s disease
|
-No glucocorticoids, body is not breaking down glycogen stores to glucose
-Usually mild, but can cause seizures |
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|
DDx for Hypercalcemia
|
-Hypoadrenocorticism/Addison’s
-Neoplasia -Renal failure -Granulomatous disease -Osteolytic disease -Hyperparathyroidism -Vitamin D toxicosis -Young animals -Idiopathic in cats -Acidosis, H ions displace Ca from albumin and Ca is free in blood -Hypothermia |
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|
Hypercalcemia and Addison’s disease
|
-Hypercalcemia should be mild, not severe
-can be profound -Without glucocorticoids, animals are unable to secrete Ca |
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|
Adrenal Axis Testing for Addison’s
|
-ACTH stimulation test is preferred test for hypoadrenocorticism/Addison’s
-Try to see if cortisol secretion can be stimulated from adrenal glands -Normal: exogenous ACTH should increase cortisol production --2 and above -Addison’s: Exogenous ACTH does not increase cortisol production, no stimulation --aldosterone concentration will also be low -expensive test! |
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|
Liver enzymes and Addison’s disease
|
-Liver is ischemic, hepatocellular damage occurs
-ALT and AST are released from hepatocytes |
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|
Aldosterone test for Addison’s disease
|
-Measured after ACTH stimulation |
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|
Treatment of Acute Addison’s crisis
|
-Fluid therapy and dextrose |
|
|
Dexamethasone for Addison’s
|
-Hold off because making a diagnosis is difficult if dex is given
-Can be given IV -Does not interfere with cortisol assay -Will suppress CRH and ACTH secretion for about 24 hours --Best to give after ACTH stimulation test |
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|
Desoxycorticosterone pivalate
|
-DOCP
-Synthetic aldosterone -Give in acute addisonian crisis -Does not interfere with ACTH stimulation test -Corrects Na:K ratio |
|
|
When to do ACTH stimulation test
|
-Before glucocorticoid administration
-Dex will not interfere with cortisol assay, but will suppress adrenal axis |
|
|
Long-term treatment of Hypoadrenocorticism
|
-Begins once animal is rehydrated, has normal electrolyte concentrations, no vomiting, diarrhea, or anorexia
-Oral supplementation of mineralocorticoid or glucocorticoid -Mineralocorticoid supplementation: --Fludrocortisone or DOCP -Glucocorticoid supplementation: --prednisone or Fludrocortisone |
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|
Monitoring of Addison’s disease by owner
|
-Can be too much or too little
-Decreased appetitie -Decreased water consumption -Lethargy, weakness, ataxia, shaking -Vomiting -Diarrhea -PU/PD -Polyphagia -Panting -Other signs of hyperadrenocorticism |
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|
Veterinary monitoring of Addison’s
|
-Physical exam
-Check response to therapy -Do not do stimulation tests -Look at Na:K ratio to see if aldosterone supplementation needs to be tweaked |
|
|
Addison’s Prognosis
|
-Excellent once crisis is over
-Average length of hospitalization is 2 days |
|
|
Feline hypoadrenocorticism
|
-Rare |
|
|
Diagnostic Imaging for Endocrine Diseases
|
-Usually not used to definitively diagnos diseases
-Used more for support of a diagnosis -Monitoring diseases over time |
|
|
Diagnostic imaging for Cushing’s disease
|
-Pituitary dependent or adrenal tumor
-Pituitary gland imaging: CT or MRI --microadenoma is most common, less than 1cm --Macroadenoma in 15-20% of dogs, more than 1cm |
|
|
Imaging the pituitary gland
|
-CT or MRI
-Only two modalities that can penetrate the skull -MRI is better for brain imaging -Hyperintense area in center represents vasopressin granules in posterior pituitary -Small lesions that will not enlarge pituitary can be identified by lack of hyperintense center --may be missed on CT, but will see on MRI |
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|
Fluid on MRI
|
-Dark on T1 image and light on T2 image
-Cavitated or cystic area |
|
|
Pituitary dependent Hyperadrenocorticism (PDH) CT imaging
|
-Microadenomas are often not visible
-Macroadenomas expand dorsally from the sella turcia --Do not cause bone destruction |
|
|
Imaging the Adrenals
|
-Ultrasound is modality of choice
--does not need anesthesia or sedation ususally -Cheaper -More widely available |
|
|
Pituitary Dependent Hyperadrenocorticism Ultrasound imaging
|
-Expect to see enlargement of both adrenal glands
--over-stimulation and over-production by pituitary tumor -Adrenals may still be within normal range of size -Should be relatively equal in size |
|
|
Adrenal Cortical Tumors on Ultrasound
|
-One adrenal is large and the other is suppressed
-Can be benign (adenoma) or malignant (carcninoma) --either can be mineralized, 50% of cases are mineralized -Adenomas will be encapsulated, 1-6cm -Carcinomas can invade along local structures --metastasize hematogenously to liver and lungs |
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Mineralization in Adrenal gland
|
-Indicates a neoplastic process
-In cats, can have mineralization in adrenal as an incidental finding |
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Adrenal tumors on Radiographs
|
-Uncommon finding
--may not be big enough to see -Will only see if mineralized -Take thoracic radiographs to rule out metastatic disease |
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Adrenal Tumor Ultrasound
|
-Unilateral
-Abnormally enlarged -Abnormally shaped -Abnormally small contralateral adrenal --suppressed by other adrenal -Uncommonly can be bilateral tumors |
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Vessels on Ultrasound
|
-Should be anechoic, contain fluid
-If dark, indicates that there is something wrong -With adrenal tumors, can see elongated neoplastic tissue occluding lumen of the vessel --adrenal tumor invades the cava -Can be a blood clot or something else |
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Adrenal tumor invading the Vena Cava
|
-If mass invades vessel, damages endothelial layer of the vessel wall
-Predisposes thrombus formation at site -Makes surgery more complicated -Prognosis is much more guarded -Neoplastic tissue invades via phrenicoabdominal vein -Can see invasion on CT |
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MRI and adrenal gland imaging
|
-Rare for adrenal gland issues
--usually ultrasound and CT give all the needed info -MRI is more expensive and takes much longer, but is possible approach |
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Adrenal tumors and Metastatic Disease
|
-Always look at liver for neoplastic spread
-Look for evidence of invasion of the vena cava |
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Cushing’s Disease Diagnosis
|
-Should NEVER be diagnosed via imaging!
-Important tool for differentiating PDH vs. adrenocortical tumor once diagnosis has been made -May see non-specific signs on radiographs also --“pot belly” --Hepatomegaly due to steroid hepatopathy and glycogen accumulation --Calcinosis Cutis --Excesive mineralization of bronchi and lungs --urinary calculi |
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Cushing’s Liver on Ultrasound
|
-Will appear large and white due to glycogen accumulation
-Steroid hepatopathy -Not pathognomonic or specific, but can support other findings |
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Calcinosis Cutis on Radiograph
|
-Can see in skin
-Indicates mineralization in the sub-cutis -Indicates Cushing’s disease |
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Non-specific diagnostic signs of Cushing’s disease on Radiographs
|
-Pot belly
-Hepatomegaly -Calcinosis Cutis -Mineralization of bronchi and lungs -Urinary calculi |
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Addison’s Disease in Ultrasound
|
-Slender adrenals, small adrenals
--depends on the size of the dog |
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Addison’s disease on Radiographs
|
-Hypovolemia due to small liver, vessels that are difficult to see and narrowed
-Microcardia -Megaesophagus (rare) |
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Hyperthyroid Radiographs
|
-Hyper-inflated lungs: lungs will look darker than usual
-Hypertrophic Cardiomyopathy: Thyrotoxic Cardiomyopathy |
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Hyper-inflated lungs on radiograph
|
-Sign of hyperthyroidism in cats
-Lungs look darker than usual -Extend more cranial than the thoracic inlet or more caudal than usual -Increased distance between the heart and the diaphragm |
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Thyrotoxic Cardiomyopathy
|
-Cardiomyopathy due to thyroid disease
-Tends to be reversible, unless it has been going on for a long time -Usually resolve with treatment of hyperthyroid disease |
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Ultrasound of the Thyroid Gland
|
-Start with a transverse image, identify the trachea
-Move from trachea to the carotid artery to find the thyroid -Between Carotid artery and the trachea |
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Thyroid gland on CT
|
-Naturally thyroid contains Iodine, will be hyper-attenuating before contrast is added
-After contrast, carotid artery and branches enhance, look similar to the thyroid -Easier on pre-contrast to evaluate the thyroid glands |
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Scintigraphy for Hyperthyroidism
|
-Can sometimes be done in hyperthyroid patient to identify function and hyperfunction
-Important if planning surgical removal -Use radioactive Technetium injected into peripheral vein for contrast -Technitium is similar radioactively to iodine, iodine pumps in thyroid gland actively trap Tch from circulation -Normal cats: thyroid and salivary glands have similar size and intensity -Hyperthyroid cats: thyroid lobes will have increased size and uptake compared to salivary glands --If unilateral, contralateral lobe is suppressed -Can identify ectopic thyroid tissue |
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Uptake of Technetium
|
-Should have uptake in:
--salivary glands --Thyroid glands --Stomach -With hyperfunctioning thyroid, will have LOTS of uptake --thyroid adenoma will show up |
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Ectopic Thyroid Tissue
|
-Can be identified with Scintigraphy
|
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Thyroid tumors in dogs
|
-Very rare
-Dogs have malignant neoplasia that can result in hyperthyroidism -Usually can palpate mass in neck area |
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Parathyroid Disease Imaging
|
-Whole body radiographs and abdominal ultrasound
-Need to rule out paraneoplastic syndrome as cause for hypercalcemia -Rule out bladder stones secondary to hypercalcemia |
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Cancers presenting with Hypercalcemia
|
-Lymphoma, esp. with cranial mediastinal mass
-Anal sac carcinomas |
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Neck Ultrasound for Parathyroid Tumors
|
-Look for thyroid gland, then look for evidence of hypoechoic nodules
-Round/oval, well-marginated nodule -More than 4-5mm, hypoechoic or anechoic comared to surrounding parenchyma -High accuracy diagnosis |
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Hyperparathyroidism secondary to Nutrition
|
-Caused by diet that has low Ca:P ratio
-Decreases serum Ca levels, decreases PTH secretion --Ca is removed from bone, causes diffuse osteopathic and pathologic fractures -Will see thin cortices, double cortical lines, decreased bone opacity, or pathological fractures on radiographs |
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Double Cortical Sign
|
-Two lines in bone cortex with radiolucency in the center
-Indicates osteopenia, any type of osteopenia -Bone resorption occurs around vessel first |
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Secondary Hyperparathyroidism on ultrasound
|
-Diffuse hyperplasia of ALL parathyroid glands
--All parathyroid glands will be visible due to enlargement |
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Pancreatic Insulinoma on Radiographs
|
-Abdomen is usually normal
-Thorax is usually normal, pulmonary metastasis is rare |
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Pancreatic Insulinoma on Ultrasound
|
-Look for mass lesion in the area of the pancreas
-Absence of mass does not rule out a tumor --may be small or poorly visualized --pancreas is surrounded by gas, can be hard to image -May see peri-pancreatic metastatic lesions and liver metastasis |
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Insulinoma on CT
|
-Dual phase angiography study
-Image the pancreas pre and post contrast administration during arterial phase and venous phase -If insulinoma is present, will see stronger arterial enhancement compared with normal pancreatic parenchyma -Pre-contrast image is not that exciting, post-contrast image will show nodules no matter how small |
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Imaging of Diabetes Mellitus
|
-Not a disease that can be imaged well
-May see concurrent disease --infection, pancreatitis, hepatomegaly due to hepatic lipidosis |
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Important points of Endocrine Imaging
|
-Endocrine disease diagnosis is usually not based on imaging |
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Histology of the Thyroid Gland
|
-Made of thyroid follicles
-One layer of cells surrounding protein-rich colloid that stains pink -Colloid: mostly thyroglobulin |
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Thyroglobulin
|
-Precursor to Thyroid hormones
|
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Formation and Secretion of Thyroid Hormones
|
-4 main steps:
--Iodide trapping --Organification --Coupling --Hormone Secretion |
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Thyroid Peroxidase
|
-Main enzyme that is responsible for thyroid hormone production
-Treatments addressing thyroid issues inhibit Thyroid peroxidase function |
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Steps in Thyroid Hormone Synthesis
|
1. Iodide trapping and transport into the cell
2. Converting Iodide to Iodine 3. Incorporating Iodine with Tyrosine, tyrosine attached to thyroglobulin -1 iodine: MIT -2 iodine: DIT 3. Coupling of Tyrosine molecules within the thyroglobulin -T4: 2 DIT coupled together -T3: 1DIT and 1 MIT coupled together 4. T3 and T4 bud off from thyroglobulin in colloid vesicles, are exported from the cell membrane |
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Transport and Metabolism of Thyroid Hormones
|
-99% of T4 and T3 are transported in plasma bound to proteins
--Thyroid Hormone Binding Globulin, transthyretin, and albumin --Serves as a reservoir for thyroid hormone -Free T3 and T4 are physiologically active -Most of T3 is made in periphery from T4 -T3 is more active than T4 |
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Formation of T3
|
-T3 is made from T4 in the periphery
-T3 is more active than T4 -80-90% of T3 is formed by deiodination of T4 in peripheral tissues --liver, kidney, muscle -To measure thyroid gland function, need to measure T4 |
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Thyroid Hormone Regulation
|
-TRH released from hypothalamus, acts on pituitary
-Pituitary secretes TSH that acts on thyroid gland -Free Thyroid hormone T3 inhibits Pituitary |
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Thyroid Hormone Actions
|
-Increases metabolic rate
-REgultes mental awareness in nervous system -Increases number and affinity of beta-adrenergic receptors in the heart --can lead to hypertrophic cardiomyopathy -Stimulates protein synthesis -Stimulates carbohydrate and lipid metabolism -Stimulates EPO -Stimulates bone turnover during growth -Stimulates neural and skeletal development |
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Hyperthyroid Diseases
|
-Clinical condition that results from excessive production and secretion of
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Hyperthyroid Diseases
|
-Clinical condition that results from excessive production and secretion of Thyroxine T4 and Triiodothyronine T3 by thyroid gland
-Most common endocrine disorder seen in cats -“New Disease,” first reported in 1979/1980 -Has become more common in last 15-20 years |
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Pathogenesis of Hyperthyroid Disease
|
-Adenomatous hyperplasia, benign hyperplasia
--Most common cause -Can be small multi-focal nodules throughout the thyroid gland or generalized hyperplasia -Similar to multi-nodular or toxic nodular goiter in humans -Usually bilateral, 70% |
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|
Histology of Adenomatous Hyperplasia of the Thyroid gland
|
-have LOTS of cells where before there was only one cell layer
-Colloid gets smaller -Lots more cellular function, lots more thyroid hormone produced |
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Thyroid carcinoma
|
-1-2% of cats with thyroid disease
-May or may not secrete excess thyroid hormone |
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Etiology of Hyperthyroid diseases
|
-Unknown!
-cat food additives? -Abnormalities in cell regulation? G-protein issue? -Circulating thyroid stimulators? -Increased awareness among veterinarians? -Probably multi-factorial |
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Signalment for Hyperthyroid diseases
|
-Middle aged to older cats, 4-22 years old
--most are more than 8 years, mean is 13 -No reported breed or gender predilection -Less common in Persian and Himalayan |
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Clinical signs of Hyperthyroid Diseases
|
-Clinical signs can be ignored by the owner for a while
-Active, ravenous cat (appears “healthy”) -Routine screening and veterinarian awareness -Weight loss with polyphagia -PU/PD -Vomiting -Diarrhea -Unkempt hair coat or alopecia -Behavior changes -Shivering/tremors -Weakness/lethargy -Heat or stress intolerance -Panting and respiratory distress -Sudden onset blindness due to hypertension -Heart failure due to up-regulation of beta-adrenergic receptors |
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DDx for weight loss with polyphagia
|
-Hyperthyroid disease
-Diabetes mellitus -Neoplasia -Protein-losing enteropathy -Exocrine pancreatic insufficiency -Parasites |
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Physical Exam of animal with hyperthyroid disease
|
-Hyperactive and difficult to exam
-Thin or cachectic -Abnormal cardiac auscultation --gallop rhythm --cardiac murmurs (50%) --tachycardia, more than 240 beats per minute -Palpable thyroid gland, can be unilateral or bilateral |
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CBC abnormalities in hyperthyroid animals
|
-Mild elevation in PCV due to increased EPO
-Increased MCV -Stress leukogram -Increased platelet size |
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Serum chemistry abnormalities in hyperthyroid animals
|
-Mild to moderate elevation of ALP and ALT
--may be severe, may get fatty infiltration due to start of hepatic lipidosis -Hyperglycemia due to stress -BUN and creatinine may be elevate due to concurrent renal disease or dehydration -Mild hyperphosphatemia -Milk hypokalemia -Creatine Kinase elevation due to muscle wasting (may be severe) |
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Urinalysis in Hyperthyroid animals
|
-Isosthenuria if there is renal insufficiency or PU
|
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Diagnostics to confirm hyperthyroid disease
|
-Do not need nuclear scintigraphy!
-Look at total T4!! |
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Total T4 concentration test
|
-Normal is between 1 and 4
-Hyperthyroid is above 4 -Useful for diagnosing hyperthyroid disease in more than 90% of cases -Should be elevated, above 4 -If lower or normal in a suspected animal, repeat in 1-2 weeks due to hormone fluctuations -Can be affected by non-thyroid illnesses |
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Free T4 concentration test
|
-Good for diagnosing HYPO thyroid disease
-Not effected by thyroid hormone binding protein levels -12-15% of normal vats with non-thyroidal illness had elevated free T4 -More sensitive and less soecific test -Only use in combination with total T4 or after total T4 -Misleading if used as only diagnostic test |
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T3 concentration
|
-Not a good measure for diagnosis of hyperthyroidism
-Mostly formed by deiodination of T4 in the tissues -T3 inhibits TSH secretion from the pituitary --should decrease T4 secretion in a normal animal -In abnormal thyroid gland, T3 will not suppress TSH release from pituitary |
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Thyroid Scintigraphy
|
-Identifies functional thyroid tissue
-Useful for finding ectopic thyroid tissue --3-5% of cats have hyperactive secreting thyroid tissue in the mediastinum -Useful to identify if one or both thyroid lobes are hyperfunctional -Can see how much tissue in each thyroid is functional -May help identify hyperthyroid cats with normal T4 -Do before sending animal to surgery |
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Diagnosing Feline Hyperthyroidism
|
-Clinical index of suspicion
-T4, CBC, chem, Urinalysis, chest rads, other ancillary tests if needed -If T4 is in normal range, repeat in 1-2 weeks --do T4 and free T4 -If T4 is still normal, screen for other diseases and perform T3 suppression test or scintigraphy |
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Treatment for Hyperthyroid disease
|
-Need to treat! Not treating is not an option, worst thing that can be done
-Medical treatment: anti-thyroid medications |
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Why treat hyperthyroid disease
|
-Elevated T4 increases GFR
--Can mask renal insufficiency -Can lead to renal failure or heart failure -Cats with overt renal failure at time of diagnosis must be managed carefully |
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Medical treatment for Hyperthyroid disease
|
-Anti-thyroid medications: Thiourelene compounds
-Inhibits thyroid peroxidase -Prevent iodine incorporation into tyrosyl groups -prevent coupling of MIT and DIT into T3 and T4 -Can directly interact with the thyroglobulin molecule |
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Methimazole
|
-Tapazole
-Main drug to use for hyperthyroid disease -Very available and inexpensive -Can control the amount of thyroid hormone produced --important if there is a renal component, renal compromise -Stabilize animals for surgery -Owners have to pill the cat every day! VERY difficult! |
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Methimazole Side effects
|
-Usually appear within the first 3 months
-Transient anorexia, vomiting, lethargy --Usually resolves quickly, can still use the drug -Facial excoriations: resolves but need to stop the drug -Hepatic toxicity: fairly rare but need to stop the drug before effects are permanent -Immune-mediated issues |
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|
Immune-mediated issues relating to methimazole
|
-Hemolytic anemia
-Leukopenia -Thrombocytopenia -Usually resolve after stopping the drug -Cannot use drug again if immune-mediated side effect arises |
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|
Methimazole Preparations
|
-Pill
-Liquid solutions, need to mix carefully --dosing is not as accurate -Transdermal preparation --each compounding pharmacy will have a different version --fewer GI side effects --Variability in absorption |
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|
Methimazole treatment regime
|
-Check for renal disease before starting
-Monitor in 1-2 weeks to make dose adjustments -Check CBC, chem, and T4 -Monitor every 2-3 weeks for first 3 months, the every 3-6 months as needed |
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|
Surgery for Hyperthyroid disease
|
-Usually need to remove both glands
-Surgery is curative -Do not need lifelong administration of medication -No monitoring of blood levels unless signs reoccur -Very useful in cases of big or cystic thyroid mass |
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|
Disadvantages of Thyroid surgery
|
-VERY EXPENSIVE!
-Requires general anesthesia and hospitalization -Very invasive surgery -May result in hypocalcemia post-surgery if parathyroid glands are removed -Hard to get ectopic hyperthyroid tissue --Do Scintigraphy before surgery! -Horner’s syndrome and laryngeal nerve damage may occur, but rare -May lead to renal failure -Hypothyroidism (rare) |
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|
Radioactive treatment for Hyperthyroidism (I-131)
|
-Take radioactive iodine I-131, give SQ
-Radioactive nucleus is unstable, undergoes decay -Hyperfunctioning gland will collect radioactive iodine --iodine concentrates in hyperfunctioning follicles -I-131 is a beta-emitter, causes local tissue damage --will kill hyperfunctional thyroid follicle cells -Halflife of 8 days |
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|
I-131 advantages
|
-One SQ injection is curative in 95% of cats
-not invasive, do not need to repeat treatment -Negligible side effects -Not invasive -Affects ectopic thyroid tissues --affects any thyroid-secreting tissue -Effective treatment for carcinoma, just need to give a high dose |
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|
I-131 disadvantages
|
-Need an authorized facility, regulated and licensed
-Cat needs to be hospitalized for radioactive clearance, away from owners -High cost --if animal lives for more than a year, becomes cost-effective -May precipitate renal failure -Cannot remove the treatment, one-shot deal -Animals may become hypothyroid (Rare) |
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|
Adjunct therapies for Hyperthyroid disease
|
-Beta-blockers:
--propanolol or atenolol --prevent heart failure -Thiamine |
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|
Prognosis for Hyperthyroid Disease
|
-Survival is good with I-131 and Methimazole
-Renal disease significantly shortens survival time -Methimazole alone: 2 years -I-131 alone: 4 years -Methimazole before I-131: 5.3 years |
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|
Nutrition and Hyperthyroid disease
|
-Y/d diet, new food from Hill’s
-Remove iodine from the diet -Seems to work OK! -Best in house with only 1 cat where diet can be strictly controlled |
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|
Treatment for Hyperthyroidism in Cats
|
-Do a treatment trial!
-I-131 treatment is best --Fewer treatments and side effects --need to make sure there is no renal disease -Important to not get to hypothyroid state |
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|
Canine Hyperthyroidism
|
-VERY rare
-Usually a malignant carcinoma in the thyroid --large and invasive -5-10% of tumors are functional -Most animals have large cervical masses at the time of presentation -Prognosis is poor to grave |
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|
Treatment for Canine hyperthyroidism
|
-Surgery
-Radioiodine (harder, need to give very high doses) -Chemotherapy -Cobalt irradiation |
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|
Hypothyroid Disease
|
-Usually affects dogs, rare in cats
--Most commonly diagnosed endocrinopathy diagnosed in dogs -LOTS of false diagnoses |
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|
Pathogenesis of Hypothyroid disease
|
-Immune-mediated
--lymphocytes infiltrate thyroid and cause inflammation, damage thyroid --histologically, will see lymphocytic infiltration -Progressive destruction of thyroid follicles -May take years to complete destruction |
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|
Thyroid Atrophy
|
-Thyroid parenchyma is replaced by adipose tissue and no inflammatory cells
-Idiopathic -End-stage lymphocytic thyroiditis? |
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|
Neopastic destruction of the Thyroid
|
-Carcinoma
-Squamous cell carcinoma |
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|
Congenital Hypothyroid issues
|
-Rare
-Thyroid agenesis -Thyroid dysgenesis -Dyshormonogenesis --follicular cell hyperplasia -Usually have other congenital issues as well -Want to prevent at an early age |
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|
Drug-induced hypothyroid disease
|
-Trimethoprim-sulfadiazine induced hypothyroidism
--May directly interfere with thyroid peroxidase activity --directly inhibits thyroid hormone synthesis -Treatments for hyperthyroidism can cause hypothyroidism |
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|
Secondary Disease of Hypothyroidism
|
-Dysfunction within the pituitary thyrotropic cells
--less TSH is produced --can be due to neoplasia or drugs -Cystic Rathke’s pouch n German Shepherds |
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|
Signalment for Hypothyroid dogs
|
-Middle-aged, big dogs
--4-10 years old -Golden retrievers, Dobermans, Labrador Retrievers -Spayed females and castrated male dogs may be at an increased risk |
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|
Clinical signs of Hypothyroidism in dogs
|
-Often is subtle and gradual onset
--Important for diagnosis! -Decreased cellular metabolism -Lethargic, exercise intolerant -Heat-seeking -Weight gain -Mental dullness, usually not obvious -Constipated -Decreased appetite with increased weight gain |
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|
Dermatologic signs of Hypothyroid disease
|
-Endocrine alopecia
--bilateral truncal alopecia, non-pruritic -Alopecic on caudal thighs -“Rat tail” -Dull, dry, flaky hair coat -Seborrhea, chronic otitis -Hyperpigmentation -Failure of hair growth -Myxedema -Secondary pyoderma |
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|
Neuromuscular signs
|
-Profound lethargy and muscle weakness
-Peripheral nerve paralysis -Laryngeal paralysis -Dragging feet -Lameness -Megaesophagus? -Slow nerve conduction velocities -Peripheral vestibular disease |
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|
DDx for megaesophagus
|
-Myasthenia gravis
-Addison’s disease -Lead poisoning -Idiopathic |
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|
Reproductive signs of Hypothyroidism
|
-Affects fertility of females, not male dogs
-Failure to cycle -Prolonged interestrous intervals -Lack of libido in the female -Hyperprolactinemia |
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|
Clinical signs of Congenital Hypothyroidism
|
-Growth retardation
-Mental retardation -disproportionately large heads -Retention of the puppy coat -Disproportionate dwarfism, retarded epiphyseal growth |
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|
Cardiovascular signs associated with Hypothyroidism
|
-Bradicardia
-Cardiac arrhythmias |
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|
Myxedema Coma
|
-Animal may present comatose
-Cerebral myxedema, swelling in the brain -Central neurological signs and seizures |
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|
Physical exam of a hypothyroid patient
|
-Mildly overweight, or severely obese
-Lethargy -Hypothermia -Bradycardia --sinus bradycardia --decreased amplitude of P and R waves -Skin disease, rat tail -Myxedema of skin |
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|
Diagnosis of Hypothyroid dogs
|
-VERY over-diagnosed disease!
-Due to dilliculties of diagnostics |
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|
Work-up for Hypothyroid disease
|
-CBC/Chem:
--mild to moderate normocytic, normochromic non-regenerative anemia --Fasting hypercholesterolemia can help identify the disease -Fasting hypertriglyceridemia -Urinalysis is usually normal |
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|
T4 measurement for Hypothyroid disease
|
-Measures totally T4 in the plasma
-Affected by MANY physiologic and pharmacologic factors --affects T4 binding proteins and pituitary-thyroid axis -Useful as a screening test, middle or high normal will reduce the chance of hypothyroidism |
|
|
Free T4 measurement
|
-Free hormone
-If low, indicates hypothyroidism -Separated by equilibrium dialysis and measured by RIA -MUCH more sensitive |
|
|
TSH measurement
|
-Used to diagnose hypothyroidism in people
-No good assays out there -Very specific when combined with total T4 -Not a valid test on its own --25-38% of hypothyroid dogs have normal TSH levels -12-38% of euthyroid dogs with concurrent illnesses have high TSH levels |
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|
Total T4 and TSH
|
-Total T4 is low and TSH is high: suspicious for hypothyroidism
-Best test for hypothyroidism when combined |
|
|
TSH stimulation test
|
-Gold standard for hypothyroid testing
-INjectible bovine TSH is off the market --expensive test to run --have to worry about anaphylactic reactions |
|
|
T3 measurement for hypothyroidism
|
-Not useful
-T3 is formed by deiodination of T4 in the tissues -Not indicative of thyroid activity |
|
|
Euthyroid Sick Syndrome
|
-physiological adaptation to decrease cell metabolism during periods of stress
-concurrent illness -Makes diagnosis of hypothyroidism difficult -Can be due to changes in thyroid hormone binding proteins --changes activation of 5-deiodinase enzymes --changes TSH secretion --Causes increased metabolism of thyroid hormone -Free T4 levels are not affected as much |
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|
Causes of Euthyroid Sick dogs
|
-Hyperadrenocorticism (Cushing’s disease)
-Diabetes mellitus -Starvation -Any concurrent disease or systemic diseases -Pyoderma |
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|
Euthyroid Sick Treatment
|
-NOT helpful to treat with thyroid supplementation!
-Treat underlying disease |
|
|
Other factors affecting Thyroid Hormone measurement
|
-Drugs:
--glucocorticoids --phenobarbitol |
|
|
Phenobarbital and Thyroid Hormone
|
-May cause decreased T4, Free T4
-Increases TSH -Makes diagnosis of hypothyroidism difficuly |
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|
Suggested approach for diagnosing Hypothyroidism
|
-Clinical index of suspicion
-Measure T4: if in upper part of reference range, hypothyroidism is low -Measure Total T4, TSH, and free T4 -Measure auto-antibodies -Elevated TSH, Low T4 and free T4: diagnose! -Trial treatment with levothyroxine, monitor response to therapy |
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|
Hypothyroid Treatment
|
-Simple treatment, give thyroid hormone!
-Sodium levothyroxine is treatment of choice --L-thyroxine -Use good generic or brand name --some compounding pharmacies will change concentration or mis-label --if need to change companies, monitor for changes in illness -Start at lower dose for dogs with cardiac illness, severely debilitated dogs, or geriatric patients -If emergency (myxedema stupor or coma) give IV L-thyroxine and supportive care |
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|
Monitoring for Hypothyroid treatment
|
-Measure T4 4-8 hours after administration
--check at peak function -T4 or free T4 should be in upper range of normal or slightly higher than normal -Adjust dose if necessary -Check pre-pill if dosing once per day -Monitor for signs of hyperthyroidism --will lead to renal and heart issues -Few side effects |
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|
Prognosis for Hypothyroidism
|
-Good if treatment is appropriate
|
|
|
Feline Hypothyroidism
|
-Rare! |
|
|
Hyperthyroidism and Hypothyroid take home message
|
-Hyperthyroidism: |
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|
Calcium in the Body
|
-More than 99% of calcium is in the bone
-Plasma calcium is present in 3 forms --bound to protein (40%) --Complexed to citrate and phosphate (10%) --Diffusable and ionized (50%) -Diffusable and ionized calcium is physiologically active and regulated form -50% of 1% is the calcium that is available and has physiologic effect |
|
|
Serum calcium
|
-Measures total calcium
-Bound, complexed, and ionized |
|
|
Ionized Calcium measurement
|
-Most accurate way to determine calcium status
-Best measured anaerobically |
|
|
pH and Calcium
|
-pH of plasma affects ratio of protein bound Ca to ionized Ca
-if pH is high, ionized Ca will be lower --more plasma protein anions to bind Ca, more Ca is bound --free Ca decreases -Decreased plasma pH (academia) results in fewer plasma protein anions --free Ca is increased -When exposed to air, serum pH usually increases and free Ca decreases |
|
|
Acidemia and Ca
|
-Acidemia results in increase in free Ca
|
|
|
Biological roles of Ca in the body
|
-Muscle contraction
-Nerve function -Blood coagulation -Enzyme activity -Cell secretion -Skeletal structure |
|
|
Endocrine regulation of Ca homeostasis
|
-Very common that patients have Ca problems
|
|
|
Vitamin D in Intestine
|
-Increases plasma Ca and phosphorous concentrations
-Intestine is the main target organ -Works on absorption of Ca and P from intestine -Formation of calcium-binding protein in the intestinal epithelial cells that actively transport Ca into the cell -Increases P absorption by unknown mechanism |
|
|
Vitamin D in Bone
|
-Works with parathyroid hormone
-Mobilizes Ca and P from the bone -Appears to be less important than parathyroid hormone PTH |
|
|
Vitamin D in the kidneys
|
-Promotes Ca and P reabsorption from the urine in the kidney
-NOT the major player -May work with PTH |
|
|
Regulation of Vitamin D secretion
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-Formation of calciferol in the kidney by 1-alpha hydroxylase
-Elevated plasma Ca has a direct effect --primarily works through decreasing PTH -Responsible for day-to-day control of Ca --not minute to minute, does not respond to changes quickly --long-term regulation of Ca |
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Parathyroid Hormone PTH
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-Synthesized and secreted by the Chief cells in the parathyroid glands
-Synthesized as part of a larger molecule --pre-pro-PTH |
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Actions of PTH
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-Bone: increases bone resorption and Ca mobilization
-Kidney: --decreases P reabsorption, increases P secretion in proximal tubules --enhances P excretion in urine --increases Ca reabsorption in distal tubules and collecting ducts --Increases formation of 1,25 dihydroxycholecalciferol |
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Regulation of PTH secretion
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-Decreased plasma Ca increases PTH secretion
-Elevated plasma Ca inhibits PTH secretion -1,25-dihydroxycholecalciferol decreases PTH synthesis --negative feedback, PTH causes vitamin D3 to be formed --too much vitamin D3 decreases PTH which decreases Vitamin D 3 production -Mg is required for normal PTH secretion and target organ responses |
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Calcium Regulation
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-PTH up, Ca is up and P is down
-Vitamin D up, Ca up and P up |
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Vitamin D vs. PTH
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-Vitamin D is a steroid, acts in intracellular receptors
--Long-acting, produces proteins --acts on GI Tract --Increases phosphorous -PTH is a polypeptide --much shorter acting --acts on bone and kidney --decreases Phosphorous |
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Calcitonin
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-Synthesized by parafollicular cells in thyroid
--C-cells produce -Small peptide, 35 KDa and 32 amino acids -Lowers circulating Ca and P levels -Inhibits bone resorption via direct effect on osteoclasts --osteoclasts are inhibited, less bone resorption -IN kidney increases Ca excretion |
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Factors affecting Plasma Ca
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-Intestinal absorption via vitamin D (IN)
-Bone resorption via PTH and vitalin D (IN) -Urinary Excretion via calcitonin, PTH and vitamin D (OUT) -Bone formation via calcitonin (OUT) |
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Ca and the Kidney
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-Ca inhibits action of ADH on collecting ducts
--no ADH action, PU/PD -Hypercalcemia may induce renal injury -Total Ca increases in renal failure -Renal secondary hyperthyroidism |
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Clinical sins of Hypercalcemia
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-PU/PD
-Muscle weakness/atrophy -Depression, coma -Anorexia, vomiting, constipation -Bone pain, pathological fractures -Signs related to specific tumors (enlarged peripheral lymph nodes -Cardiac arrhythmias (prolonged P-R and shortened Q-T intervals |
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PU/PD due to hypercalcemia
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-Ca interferes with ADH receptors in collecting duct
-Ca uroliths can cause problems -usually the first sign that is noticed by the owner --sometimes the only sign |
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Primary Hyperparathyroidism
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-Parathyroid gland is overactive, secretes too much PTH
-Relatively uncommon in dogs -Rare in cats -Can be due to Adenoma, carcinoma, hyperplasia, ectopic parathyroid tissue |
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Clinical signs of Hyperparathyroid disease
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-Signs are often absent in mild forms of the disease
-Signs associated with hyperclacemia --PU/PD --anorexia --depression -As hypercalcemia progresses, severe illness and organ failure may occur -Usually will not result in renal failure because P is decreased |
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Physical exam for patient with hyperparathyroidism
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-Often normal PE
-Non-specific abnormalities -Rare that you can feel an enlarged parathyroid -Ca uroliths may be present -Ca will be high -PTH will be normal to elevated -measure PTH and Ca at the same time --if Ca and PTH are both increased, know there is an issue -P will be normal to low, relative “protective” effect on the kidneys |
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Hypercalcemia of Malignancy
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-Most common and important cause of hypercalcemia in dogs
-Caused by release of a factor by a tumor --PTH-related hormone (PTHrP) --causes up-regulation of osteoclast activity in bone -Leads to bone resorption -Lymphoma, anal sac carcinoma |
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Lymphoma and hypercalcemia
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-Commonly produces hypercalcemia in dogs
-Cats are usually FeLV negative -PTHrP is isolated from dogs and cats with lymphosarcoma |
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Multiple myeloma and hypercalcemia
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-Malignant plasma cells
-can be in bone marrow -Osteoclast-activating factor -Causes bone changes -Seen in cats and dogs |
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Apocrine cell Adenocarcinoma of the Anal Sac
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-Hypercalcemia due to humoral factors
-80-90% of dogs have hypercalcemia -Older females are predisposed, can see in either sex |
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Common tumors causing Hypercalcemia
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-Lymphosarcoma (top 9 cancer causes of hypercalcemia)
-Multiple myeloma -Anal sac adenocarcinoma -mammary gland carcinoma -Lymphocytic leukemia -Carcinomas of lung and thyroid -Testicular interstitial cell tumors -Metastatic squamous cell carcinoma in cats |
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Renal disease and hpercalcemia
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-Most patients with chronic or renal disease are normocalcemic
-May see increased complexed Ca due to retention of ligands -Some patients may have true ionized hypercalcemia --maybe related to acidosis? |
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Hypoadrenocorticism and hypercalcemia
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-Increased Ca caused by glucocorticoid deficiency, hyperproteinemia, increased renal Ca reabsorption
-May also cause hypocalcemia -uncommon cause, but can happen |
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Other causes of Hypercalcemia
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-Hypervitaminosis D
--rodenticides --skin creams -Granulomatous disease --fungal infections |
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Feline Idiopathic Hypercalcemia
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-Most common cause of hypercalcemia in cats
-Syndrome of young to middle-aged cats -Mild to moderate hypercalcemia for months to years -Can cause vomiting and weight loss -Dietary factors? Increased dietary fiber? Mg limited diets? Dietary acidification? |
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HARD-IONS
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-Hyperparathyroidism
-Addison’s Disease (hyperadrenocorticism) -Renal disease -Vitamin D toxicosis -Idiopathic -Osteolytic -Neoplasia -Spurious (lipemia) |
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Hypercalcemia
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-Elevated ionized Ca
-False elevations can be caused by many factors --elevated total protein, especially albumin --serum lipemia --renal failure due to increase in complexed Ca |
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Diagnostics for Hypercalcemia
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-CBC
-Chemistry: check albumin levels and renal function -Urinalysis: look for UTI -Ionized Ca: confirm hypercalcemia -ACTH stimulation test to rule out Addison’s disease -Aspirate lymph nodes, even if they feel normal --Lymphoma is so common it is worth doing -Radiographs -Ultrasound -Bone marrow exam -Check PTH levels |
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Radiographs for hypercalcemia diagnosis
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-Chest, abdominal, skeletal radiographs
-Look for metastatic disease -Look for bony lesions on skeleton |
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Ultrasound for Hypercalcemia diagnosis
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-Abdomen: look for neoplasia
-Neck: assess parathyroid glands |
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Bone marrow analysis for hypercalcemia diagnosis
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-Look for hematologic cancer
-Sometimes is the only tissue that can provide a diagnosis |
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PTH levels for Hypercalcemia
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-Need ionized Ca levels at the same time
-Elevated PTH levels with hypercalcemia strongly suggests hyperparathyroidism -PTH can also be normal with hyperparathyroidism -Also elevated in renal failure |
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PTHrP levels for hylercalcemia
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-Elevated concentrations of PTHrP are associated with tumors
--Lymphoma --anal sac adenocarcinoma -If levels are normal, does not rule out neoplasia |
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Vitamin D levels for Hypercalcemia diagnosis
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-Can be useful if hyperphosphatemia is also present
-Indicates rodenticide poisoning, vitamin D over-supplementation, or granulomatous disease |
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Treatment for Hypercalcemia
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-Treat underlying condition
-Surgical removal of parathyroid mass -Ethanol injection or heat ablation of parathyroid tumors -Chemotherapy for neoplasia |
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Surgical removal of parathyroid masses
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-Closely monitor post-surgery, animals often become hypocalcemic
--other glands will have atrophied, takes time for them to become functional -Rarely the disease may recur, may need further surgery -Ultrasound-guided ethanol injection or heat ablation or Parathyroid tumors |
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Neoplasia treatment for Hypercalcemia
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-Chemotherapy or surgical intervention of underlying neoplasia
-Often resolves hypercalcemia |
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Emergency treatment for Hypercalcemia
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-Indicated when there are severe clinical signs
-Cardiac arrhythmias -Renal failure -Ca x P is more than 60 mg/dl -Give IV fluids, 0.9% NaCL --natriuresis promotes calciuresis -Furosemide promotes natriuresis and calciuresis |
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Bisphosphanates as treatment for Hypercalcemia
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-Inhibit osteoclast activity
-Decrease Ca and P -Long-acting, can be used to manage patient until specific diagnosis is reached -Useful in vitamin D toxicity -May be useful in feline idiopathic hypercalcemia -Pamidronate, clodronate, alendronate |
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Calcitonin as treatment for Hypercalcemia
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-Increases secretion of Ca in kidneys
-Salmon calcitonin is most often used, more potent than human or dog calcitonin -Commercially available -Very expensive -Can be given IV or SQ |
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Corticosteroids as treatment for Hypercalcemia
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-Glucocorticoids promote calciuresis, gets rid of Ca
-Should not be used until Lymphoma has been ruled out! --steroids are lymphotoxic, may induce multiple drug resistance -Interfere with testing for hypoadrenocorticism (Addison’s Disease) |
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Primary Hypoparathyroidism
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-Failure of PTH action
-Iatrogenic -Idiopathic -Pancreatitis -Intestinal malabsorption -Phosphate enemas -MUCH less common than hypercalcemia |
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Idiopathic primary hypocalcemia
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-Lymphocytic parathyroiditis, immune system attachs parathyroid
-Lack of circulating PTH levels -Occurs in young, or mature dogs |
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Iatrogenic Primary Hypocalcemia
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-Parathyroid glands are injured or removed during thyroid surgery
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Eclampsia
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-Occurs during first 4 weeks of lactation
-Clinical signs develop rapidly -Often concurrent with hyperthermia and hypoglycemia -Due to poor nutrition? -Excess Ca supplementation? |
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Intestinal malabsorption leading to hypocalcemia
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-Lymphamgectasia
-May be concurrently hypomagnesemic |
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Clinical signs of Hypocalcemia
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-Caused by excitatory effects of hypocalcemia on nerve and muscle cells
-Muscle twitching, cramps, tremors, tetany -Lethargy, restlessness, seizures -Cataracts are common in hypocalcemic people, rarely seen in dogs |
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Diagnostics for Hypocalcemia
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-CBC, Chem, urinalysis
-Measure ionized Ca -Serum magnesium --important for management of the patient --hypomagnesemia can cause hypocalcemia on its own -Check PTH levels |
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PTH and hypocalcemia
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-Low normal or decreased PTH with hypocalcemia indicates primary hypoparathyroidism
--should increase when Ca decreases -Check ionized Ca on same blood sample for comparison -PTH level means nothing on its own |
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Treatment for Hypocalcemia
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-10% Calcium gluconate
-Give slowly, IV over 15-30 minutes -Monitor ECG -Can give as CRI or intermittent SQ injection |
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Treatment of Acute hypocalcemic patient
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-Vitamin D and oral Ca supplementation
--begin as soon as oral medication can be tolerated -After 1-2 days of normocalcemia with oral Ca and vitamin D, can discontinue parenteral Ca |
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Vitamin D therapy
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-Vitamin D2 is the active form
--inexpensive, fat soluble, takes longer to raise serum Ca and takes longer to go away --hard to regulate -Dihydrotachysterol: works more quickly --more expensive, easier to regulate -Vitamin D3 (Calcitriol) |
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Vitamin D3 Calcitriol
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-More rapid onset
-Biologically active compound --can use physiological doses -Goes away quickly -more expensive -May have to reformulate capsules since doses are usually too large for dogs and cats |
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Calcium supplementation
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-Start at 25mg/kg/day during initial vitamin D therapy |
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Pet Obesity
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-40-50% of pet population is over-weight or obese
-Especially in middle-aged dogs, 5-11 years old |
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Health Risks associated with Pet Obesity
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-Glucose intolerance
-Abnormal insulin secretion -Skin problems -lameness -FLUTD (cats) -Idiopathic hepatic lipidosis |
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Orthopedic disease and Obesity
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-Dogs with more weight have vastly increased orthopedic problems
-Earlier onset of osteoarthritis and greater proportion of animals -Not obese dogs, just dogs that are “carrying around a few extra pounds” |
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Factors promoting Weight gain in Animals
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-Animal factors
-Environmental factors -Human companion factors |
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Animal factors contributing to weight gain
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-Instinct to gorge
--unenriched, bored animals -Feline metabolism -Neutering |
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Effect of Neutering
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-Neutered cats are 3.4 times more likely to be overweight than intact cats
-Increased food intake -Decreased energy expenditure |
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Environmental factors contributing to weight gain
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-Indoor confinement
-Palatable, energy dense foods -Free choice feeding -Multi-pet households |
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Human factors contributing to weight gain
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-Perception of body condition
-Human-animal bond and sharing food/treats |
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Energy Balance for pets
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-Energy intake vs. energy expenditure
-Want energy intake = energy expenditure -Energy expenditure is based on lean tissue energy expenditure, NOT fat --lean tissue, organ tissue, brain, heart, kidney, liver -Resting energy requirement is the same whether the animal is overweight or not |
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Weight loss program for Pets
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-Physical exam
-Medical history and emphasis on dietary information -Estimate of lean body weight -Estimate of current energy intake -Formulate the treatment plan -Monitor and adjust ongoing treatment program |
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Diet History
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-Specific varieties and amounts of commercial foods fed
-Client may need to go home and check labels -Need to know can size! -Need to know how dry food is measured (if it is measured) -May need to keep a food diary -Who lives in the household -Other pets in the household and feeding strategy -Method of feeding -Treats --dental treats, rawhides, etc. -Table foods -Food to give pills -Hunting or scavenging -Activity level |
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Identify problem areas based on diet history
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-Over-indulgence
-Begging -Multi-pet household -Sedentary lifestyle |
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Estimating optimal weight of a patient
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-Breed standards
-Taking specific measurements to estimate percent body fat -Check medical records -Use body condition score --10% for each level over optimal |
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Best weight loss program
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-Caloric intake
-Exercise -Behavior modification -60-70% of current intake, feed 60-70% of estimated maintenance energy requirement |
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Targeting rate of weight loss
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-1-3% of total body weight per week
--Safe weight loss without rebound -No published studies in cats -One published study in dogs |
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Poteintial problems
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-Animal is “starving”
--feed multiple small meals per day --Add non-starchy vegetables --food puzzles -Other people in the household -Multi-pet households |
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Carbohydrates
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-Not the carbohydrate in diet that makes the difference
-Calorid density is the big deal -Macronutrient profile -Fiber and water dilutes calories --canned food is less calorically dense |
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Therapeutic weight loss diets
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-Valuable for weight loss programs
-Low calorie density -Fortified with essential nutrients -High protein, preserves lean body mass -Greater satiety? |
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Important points of Obesity in pets
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-Obesity in companion animals is prevalent and has health consequences |
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