Endocrinology Flashcards

Question

What is this? Who is it common in? What is the most likely cause? What occurs?

Answer 1

Congenital hypothyroidism \* Common in lambs, other species rarely affected - typically due to iodine deficiency - usually weak or stillborn and may have goiter \* Congenital cases may display certinism (severely stunted mental and physical growth) - disproportionate dwarfism with long limbs, short bodies, and domed heads with shortened muzzle - mental impairment common - retention of juvenile hair coat (fine hair)

Answer 2

Adult-onset hypothyroidism \* Common in dogs, rare in other species Causes: 1. lymphocytic thyroiditis- bilateral invasion and destruction of thyroid tissue by lymphocytes, unknown cause -- affected animals often develop antibodies directed against thyroglobulin and other thyroid hormones 2. Idiopathic follicular atrophy- may represent end stage of lymphocytic thyroiditis but inflammation usually minimal-- thyroid follicles are small and sparsely distributed with adipose tissue infiltration \* Vague and insidious course \* Decreased metabolic rate - mental dullness - exercise intolerance - cold intolerance - weight gain other: - poor coat quality, hyperpigmentation, alopecia, seborrhea and hyperkeratosis, secondary pyoderma and otitis externa, myxoedema- non-pitting oedematous thickening of the forehead, eyelids, and skin folds of the face and neck-- "tragic facial expression-- due to subcutaneous accumulation of hydrophyllic glycosaminoglycans \* may be infertile, megaoesophagus due to neuropathy affecting oesophageal innervation, bradycardia with absence of thyroid homrone (severe cases hypotension, hypothermia, become comatose), hyperlipidaemia prediposes to atherosclerosis (severe cases may develop infarction, corneal lipidosis are common)

Answer 3

\* Decreased thyroid functional tissue- aplasia, hypoplasia (rare), thyroid atrophy, typically due to decreased TSH stimulation \* Thyroid destruction: immune mediated thyroiditis, neoplasia (destructive thyroid carcinoma), iatrogenic (e.g. thyroidectomy to remove thyroid neoplasia, overdose of thyroid hormone inhibitor) \* Impaired thyroid hormone production (usually associated with goiter) - dietary iodine deficiency, dietary iodine excess, enzyme defects in thyroid hormone synthesis, exposure to goitrogenic toxins which interfere with thyroid hormone synthesis

Answer 4

\* Non-inflammatory and non-neoplastic thyroid enlargement \* typically associated with hypothyroidism (nodular hyperplasia is the exception) \* Occur sporadically in calves, lambs, kids and pups due to inability to synthesize thyroid hormone

Answer 5

1. Hyperplastic goiter- reflects hypersecretion of TSH and hypertrophy and hyperplasia of thyroid tissue without adequate thyroid hormone production-- inadequate T3/T4 so feedback does not work and just continues secretion of TRH and TSH--\> hypertrophy & hyperplasia--\> thyroids are diffusely enlarged, firm, dark red with a "meaty" texture due to increased cellularity and blood flow-- animals may be weak poorly haired, and display myxoedema \*\* most cases reversible 2. Colloid goiter: reflects the resolution stage of hyperplastic goiter once thyroid hormonal function has been restored- restoration of normal T3/T4--\> decreased TSH stimulation of thyroid--\> follicular atrophy and accumulation of colloid within follicles. Thyroids are diffusely enlarged pale tan coloured with a waxy appearance on cut surface. 3. Nodular hyperplasia- idiopathic hyplasia of thyroid tissue, common in older cats, dogs and horses. Mat be associated with hyperthyroidism inc ats, but not typically an indicator of hypothyroidism and often incidental findings

Answer 6

\* iodine deficiency (usually seen in mountain and inland areas- seawater is rich in iodine), causes hyperplastic goiter, rarely observed now due to supplementation \* iodine excess- may also cause hyperplastic goiter as excess iodine impairs uptake by thyroid gland and thyroid hormone synthesis, usually associated with overzealous supplementation, neonates and fetuses more sensitive due to concentration of iodine in palcenta and milk. \* Goitrogenic toxins- some toxins interfere with the SYNTHESIS of THYROID HORMONES (e.g. goitrin, derived from glucosinolates in Brassica plant spp.) causing hyperplastic goiter \* Congenital dyshormonogenetic goiter: hyperplastic goiter due to genetic defects in ENZYMES responsible for thyroid hormone synthesis

Answer 7

hyperplastic goiter

Answer 8

hyperplastic goiter

Answer 9

\* Clinical features: increased metabolic rate (weight loss, polyphagia, hyperactivity/ irritability); skin (unkempt hair coat/ patchy alopecia); Cardiac effects (arrhythmias, secondary hypertrophic cardiomyopathy, hypertension)

Answer 10

Causes of hyperthyroidism

Answer 11

\* Four glands in most species that are associated with thyroids: one pair within the thyroid parenchyma and an external pair \* composed of chief cells which secrete parathyroid hormone (PTH) \* C Cells- interstitial cells within the thyroid secrete calcitonin-- usually individually cells or small clusters that sit between thyroid follicles

Answer 12

\* Opposing effects on serum calcium - PTH: provides general regulation of serum calcium concentrations, secretion induced by decrease in serum calcium as well as phosphate, promotes renal calcium retention and phosphorous excretion, increases osteoclastic bone resorption, promotes synthesis of active vitamin D3 - Calcitonin: provides emergency regulation in the event of hypercalcaemia, secretion induced by increase in serum calcium, promotes renal calcium and phosphorous excretion, inhibits osteoclastic bone resorption

Answer 13

Occasionally seen in small animals, rare in other species \* Causes: due to lymphocytic plasmacytic parathyroiditis (presumed autoimmune parathyroid destruction), occasionally induced by thyroidectomy \* Effects: reflect decreased PTH secretion and hypocalcaemia, clinical effects typically develop suddenly and are episodic, animals develop tremors/ tetany, hyperpnoea and are often hyperexcitable- seizures may occur in severe cases, muscle weakness and arrhythmia may also develop

Answer 14

\* Complex metabolic disease in cattle (milk fever/ parturient paralysis) and sometimes in dogs (eclampsia) \* Cause: high dietary calcium intake during pregnancy suppresses the PTH secretion and increases calcitonin secretion, leading to decreased calcium mobilization--\> following parturition, calcium demand increases markedly due to lactation, while calcium intake is decreased due to inappetance and post-partum GI stasis--\> PTH unable to respond rapidly to changes in calcium supply and demand--\> hypocalcaemia develops Effects- downer cows, dogs show overstimulation

Answer 15

Parathyroids

Answer 16

Parathyroid gland

Answer 17

C cells- interstitial cells within the thyroid that secrete calcitonin

Answer 18

Hyperparathyroidism- Causes: older dogs, caused by excessive PTH, functional parathyroid neoplasia (adenoma (B) or carcinoma (M))

Answer 19

Secondary RENAL hyperparathyroidism: \* Caused by hypocalcaemia or hyperphosphataemia- renal tubular defects causing increased calcium excretion and phosphate retention (phosphate binds calcium), decreased vitamin D synthesis \* Parathyroid hyperplasia and PTH hypersecretion secondary to hypocalcaemia in renal failure \* all parathyroids enlarged (due to hyperplasia stimulated by calcium imbalance, in contrast to parathyroid neoplasia which affects a single gland)

Answer 20

Secondary Nutritional hyperparathyroidism \* Parathyroid hyperplasia and PTH hypersecretion secondary to low dietary calcium and/or dietary phosphorous (phosphate binds calcium) \* Commonly induced by: all meat diets (dogs, reptiles), high concentrate diet especially bran (horses), diets high in oxalates (oxalates bind calcium) \* all parathyroids enlarged (due to hyperplasia stimulated by calcium imbalance, in contrast to parathyroid neosplasia which affects a SINGLE GLAND)

Answer 21

\* osteoporosis due to osteoclastic bone resporption and demineralization \* susceptible to pathological fracture- folding fractures common, animals may develop shifting lameness due to microfractures or paressis due to spinal fracutres \* Facial bones most severely affected -- fibrous tissue may result in firm swellings ("big head" in horses) \*\* Metastatic MINERALIZATION- only occurs in primary hyperparathyroidism due to hypercalcaemia (because secondary is a response to low calcium and so calcium levels are typically low)-- lungs, stomach, kidneys, and blood vessels (including endocardium) most commonly affected

Answer 22

Osteoporosis from hyperparathyroidism

Answer 23

Fibrous osteodystrophy- from hyperparathyroidism

Answer 24

Fibrous osteodystrophy- hyperparathyroidism

Answer 25

Rubber jaw- hyperparathyroidism

Answer 26

Aka hypercalcaemia of malignancy \* secretion of parathyroid hormone- related protein (PTHrP) by some neoplasms - anal sac apocrine adenocarcinoma, Lymphoma (especialy T cell) \* Causes soft tissue mineralization- renal, gastric, mammary carcinomas, SCC (especially gastric SCC in horses) Effects: similar to primary hyperparathyroidism but less bone resorption; major effects are hypercalcaemia and metastatic mineralization

Answer 27

\* Rare but in horses and old bulls \* Adenomas are circumscribed, encapsulated, firm, cream to grey- tan, one or many \* Carcinomas may be unilateral or bilateral, locally invasive, may metastasize to LNs and lungs \* In bulls, C cell tumours may be present concurrently with pheochromocytoma +/- pituitary adenomas \*\* C cell tumours in bulls may be functional and cause vertebral spondylosis and osteopetrosis- hypocalcaemia is typically mild \*\* C Cells in horses is usually solitary and asymptomatic

Answer 28

\* uncommon, seen in dogs and ferrets; islet of langerhans produce insulin, glucagon, somatostatin, and others. 1. Insulinoma- episodic seizures, weakness and collapse, reflecting CNS glucose depletion, triggered by fasting, exercise or excitement, episodes are brief due to counter-regulatory hormones (catecholamines, glucagon, cortisol, and growth hormone) 2. Gastrinoma- not normally produced by islets of langerhan but may be in neoplasm-- causes Zollinger-Ellison syndrome- increased gastric acid production therefore gastric and duodenal erosions and ulcerations; anorexia, melaena and/or haematemesis 3. Glucagonoma- rare, hyperglycaemic (may develop diabetes mellitus due to insulin resistance) and display vacuolar hepatopathy, superficial necrolytic dermatitis (aka hepatocutaneous syndrome)-- bilaterally symmetrial hyperkeratotic crusting, lesions of muzzle, lips, periocular skin, pinnal margins, distal extremities, ventrum, pressure points (hocks), external genital mucocutaneous margins. Footpads are hyperkeratotic.

Answer 29

The CNS cannot synthesize, store or concentrate glucose-- hypoglycaemia ultimately leads to coma and death.

Answer 30

Exocrine= glands that produce and secrete substances onto an epithelial surface by way of a duct, in the case of the pancreas this refers to its function in the GIT Endocrine= Secretes hormones using ducts. In the case of the pancreas, this refers to the Islets of Langerhans

Answer 31

\* Insulin, glucagon, somatostatin, pancreatic polypeptide \* GlucAgon- catabolic hormone secreted by ALPHA cells-- increased insulin & increased somatostatin secretion-- Role is to maintain NORMOGLYCAEMIA \* Insulin- anabolic hormone secreted by BETA cells-- decreased glucagon secretion-- ALLOWS the body to use carbs as energy sources and to store nutrients. Causes tissue uptak and sequestration of glucose, fatty acids, and amino acids with resultant DECREASE IN PLASMA LEVELS. \* Somatostatin- secreted by delta cells-- inhibits digestive processes and other pancreatic hormones-- decreased insulin & decreased glucagon secretion-- INHIBITS glucagon and insulin \* Pancreatic polypeptide- secreted by F cells-- increases gut motility and gastric emptying

Answer 32

\*\* Hormones are secreted into pancreatic vein--\> portal vein--\> preferentially affects liver \* innervated by the sympathetic and parasympathetic NS

Answer 33

1. High blood glucose (most important stimulant) 2. Blood amino acid (arginine and alanine) 3. Gastrointestinal hormones e.g. cholycystokinin 4. Parasympathetic stimulation Insulin secretion is inhibited by: 1. Low plasma glucose (fasting, exercise) 2. Somatostatin sympathetic stimulation 3. Sympathetic- alpha adrenergic activity

Answer 34

1. In the acute phase (10 minutes) release of preformed insulin occurs 2. In the chronic phase (rises over next hour) release of newly formed insulin occurs. \*\* from beta cells of the pancreas directly into the portal vein which ensures the liver receives high concentrations 1/2 life of insulin in blood is 5-8 minutes \*\* metabolized by the kidney and liver by the enzyme inulinase that splits disulphide bonds

Answer 35

Allows the body to use carbohydrates as energy sources and store nutrients. Causes tissue uptake and sequestration of glucose, fatty acids, and amino acids with resultant DECREASE in plasma levels. Toward hypoglycaemia because it is storing!!!

Answer 36

Caused by either inadequate insulin secretion or inappropriate insulin action on target tissues and therefore hyperglycaemia and can contribute to Type I or Type II diabetes mellitus.

Answer 37

1. Glucose influences Beta islet cells electrical activity via metabolically inudced changes in the activity of ATP-sensitive K+ channels 2. These channels open when glucose is low and close when glucose is high 3. ATP blocks K+ channel activity, whereas ADP stimulates K+ channel opening. (common target for anti-diabetic drugs) 4. Depolarizing cell membrane opens voltage- gated Ca2+ channels and results in both synthesis of insulin and exocytosis of insulin granules leading to insulin secretion

Answer 38

\* Insulin binding alpha and beta subunits of tyrosin kinase--\> allowing the receptor to phosphorylate tyrosine residues --\> ACTIVATION OF PIP2 pathways and MAP kinase pathways--\> OVERALL a result in a range of GENES and ENZYMES activatied which have important roles in increased glucose uptake and storage, protein synthesis and lipogenesis.

Answer 39

\* Promotes glycolysis (liver, pyrvate+ lactate--\> glucose), lipogenesis, and inhibits glycogenolysis (liver, glucose output) with major targets being the liver, adipose tissue, and muscle. \* Muscle--\> stimulates glucose uptake via carrier system, Glut4, stimulates glycolysis, stimulates glycogen synthesis, promotes protein synthesis \* Adipose tissue--\> stimulates glucose uptake via Glut4, glycolysis, some effect on protein metabolism, stimulates fat deposition, regulates lipoprotein lipase which promotes breakdown of triglycerides in blood (VLDL & chylomicrons) to free glycerol and free fatty acids

Answer 40

Essentially opposite to insulin-- the role is to maintain normoglycaemia. Secreted by the ALPHA cells of the pancreas. Half life of 6 minutes in the blood. 50% extracted by the liver on single pass. 1. Secreted in response to low plasma glucose 2. Stimulated by protein meal 3. Inhibited by insulin and somatostatin MOST IMPORTANT ACTION= maintenance of hepatic glucose output \* little effect on glucose utilisation \*\*\*\* insulin and glucagon control the relative rates of gluconeogenesis and glycolysis by altering the hepatic fructose 2,6-biphosphate levels plus other key enymes involved in glycolysis

Answer 41

\* Stimuli for secretion: 1. Glucose, amino acids, free fatty acids, gastrointestinal hormones, glucagon & autonomic stimuli 2. Inhibition of secretion: autonomic stimuli & insulin Actions: 1. inhibition of insulin and glucagon 2. reduces assimilation rate of all nutrients from GIT. Prevents rapid nutrient overload.

Answer 42

A condition in which large amounts of glucose are excreted in the urine instead of supplying the muscles and organs. Untreated suffer from periodic energy supply crises- severe weakness and occasionally diabetic coma. The paradox is that animals are not malnourished and indeed contain an abundance of biological fuel which cannot be "burnt." \*\* Type 1-- underproduction of the hormone insulin, which the function of insulin is to open the glucose "gates" of cells for storage, and in the absence, the gates remain shut and cell starved of glucose.

Answer 43

\*PU/PD, high glucose in urine, excretion in ketone bodies, acetone smelt on breath, etc. \* e.g. normal blood glucose is about 4mM, but in diabetic dogs and cats it can exceed 8mM-- renal threshold is 7mM and is excreted in high amounts

Answer 44

\* Chronic disorder of carboyhydrate metabolism. results in hyperglycaemia due to absolute or relative insulin insufficiency or reduced sensitivity of target cells. \* The primary problem in all forms of diabetes mellitus is the inability to conduct glycolysis despite an abundance of blood glucose for 2 reasons 1. In the absence of normal insulin responsiveness, glucose cannot enter cells at a normal rate and therefore blood glucose cannot be utilized. Brain and liver are exempt from this problem in diabetes because uptake of glucose does NOT depend on insulin. Brain can utilize ketone bodies. Insulin's effect on muscle cells is to promote expression of gates called Glut4-- this doesn't happen without insulin. 2. Glucagon, present in normal levels in diabetics promotes gluconeogenesis and glycogen degradation in the liver. IN heart muscle and other tissue glucagon promotes glycolysis. The overall effect of this hormonal imbalance in the diabetic is for the liver to degrade valuable glycogen to glucose which is released into the blood and finally voided in the urine. Gluconeogenesis in the liver is inappropriately promoted and glycolytic intermediates are diverted from the production of oxaloacetate via the anaplerotic reactions.

Answer 45

Also called insulin dependent diabetes mellitus (IDDM) The most common type but seems to develop mainly in middle age or in older animals. \* Dogs manufacture littler or no active insulin due to an immune attack. \* Susceptiblity is inherited in most cases, the trigger is unknown. \* Pancreatitis is often seen as well \* generally managed by SQ admin of insulin

Answer 46

\* Non-insulin dependent diabetes mellitus (NIDDM) \* most common type in humans and in cats \* it also occurs in dogs but less commonly \* Burmese cats especially \* Typified by a lower sensitivity to low doses of insulin than type 1 disease. Primarily due to reduced production of insulin and increase insulin resistance. Loss of sensitivity to insulin; often the problem is that insulin receptors are under-expressed. Sometimes this is linked to OVEREATING!! \*\* Diabetes in cats normally has degenerative lesions due to amyloid deposition within the islets of Langerhans, whereas the remainer of the pancreas appears to be normal-- possibly by increased glucose toxicity or underlying infectious/ inflammatory process \* Treatment- glargine (tradename lantus): this is the preferred insulin cats-- exercise and diet changes

Answer 47

The body has the ability to use amino acids-- therefore a high protein diet is often recommended. However, large amounts of urea are produced which must be excreted along with commensurate amounts of water.

Answer 48

\* Under normal circumstances glucagon promote the release of fatty acids from triglycerides stored in lipoproteins into the bloodstream; the primary enzyme which glucagon actives is called hormone sensitive lipase. Insulin inhibits this enzyme. Thus the absence of insulin causes excessive release of fatty acids into the blood. Additionally, insulin promotes transfer of triglycerides from blood lipoproteins to vascular endothelial cells; the key enyme here is called lipoprotein lipase. THEREFORE absence of insulin = FAT ACCUMULATING IN THE BLOOD

Answer 49

\* Osmotic diuresis- water following the glucose--\> dehydration--\> Polydipsia

Answer 50

Glucose! Beta cells monitor levels of glucose, leucine, and alanine

Answer 51

\* Promotes storage of glucose as glycogen as well as conversion of glucose to triglycerides

Answer 52

1. Insulin stimulates Glut4 in muscle and adipose 2. Enhances conversion glucose to glycogen 3. Increases glucose breakdown oxidation phosphofructokinase pyruvate dehydrogenase 4. Stimulates the synthesis of protein in skeletal muscle and slows the degradation of existing proteins

Answer 53

Type II Diabetes Mellitus

Answer 54

\* Glucose unavailable for use--\> fatty acids used for ATP production \* Ketone bodies are produced--\> accumulate--\> Ketone acidosis--\> increased H+ = brain dysfunction and contributes to coma and death

Answer 55

Cataracts-- as blood glucose increases some tissues convert the glucose into sorbitol-- sorbitol does not cross cell membranes and therefore accumulates intracellularly producing osmotic swelling, hypoxia and damage--\> Reduced transparency of the lens (cataracts) \*\* Neurons, kidneys, blood vessels and the lens f the eye have aldose reductase which means glucose can be converted to sorbitol in these cells

Answer 56

\* Cats \> 8 yo, usually autonomous release of T4 and T3, neoplasia is uncommon but can occur-- would be functional adenocarcinoma if resulting in hyperthyroidism \*\* in 90% of cats palpable mass, 70% bilateral too

Answer 57

Heinz body from endogenous oxidative stress- damage to hemoglobin from ROS- leading to premature cell lysis. Can indicate hyperthyroidism, paracetamol and onions by cats, dogs.

Answer 58

\* Mild to moderate increases in liver enzymes are the most common alternations-- elevated ALT (secondary liver disease), elevated ALP, +/- AST (up to 90% have at least one liver enyme abnormality) \* Azotaemia (20%)- concurrent renal disease, dehydration \* Elevated UPC (75%)- proteinuria is common due to hypertension \* Hyperglycaemia (5%)- stress- related or concurrent diabetes mellitus

Answer 59

\* Serum total T4 (TT4) (90% elevated, 10% within reference) - initial screening test of choice \* If normal but still suspect hyperthyroidism, REPEAT TT4 at later date if signs are mild--\> measure free T4 (higher sensitivity; less affected by non-thyroidal illness; especially useful when TT4 is high normal) \*\* You can also use T3 suppression test- no change in T4 lelve with hyperthyroidism as TSH is already suppressed OR Thyroid scintigrpahy

Answer 60

\* CBC, serum biochemistry, urinalysis (looking for high protein due to hypertension), serum total T4 concentration (TT4), thoracic imaging, measure blood pressure, then if TT4 borderline high, repease at a later date or measure free T4

Answer 61

Renal disease can mask hyperthyroidism & Hyperthyroidism can mask chronic kidney disease (via increase renal perfusion) and also exacerbate renal disease (via renal hypertension) \*\* assessment of renal parameters is recommended before using definitive treatment for hyperthyroidism e.g. start with oral anti-thyroid drugs that are reversible before surgical thyroidectomy or radioactive iodine

Answer 62

Hypothyroidism \* Impaired production and secretion of thyroid hormones resulting in a decreased metabolic rate Primary hypothyroidism (95%)- thyroid gland dysfunction e.g. lymphocytic thyroiditis or thyroid atrophy Secondary hypothyroidism (5%)- pituitary dysfunction (impaired TSH secretion) e.g. congenital-- pituitary dwarfism, drugs, neoplasia \*\* rare in cats but can occur iatrogenic post treatment for hyperthyroidism

Answer 63

\* Mild normocytic normochromic non-regenerative anaemia (30%)- likely due to decreased erythrocyte production \* Codocytes can be seen- reduced quantity of intracellular hemoglobin in hypothyroid patients

Answer 64

\* hypercholesterolaemia (75%)- hypertriglyceridaemia is also common (decreased hepatic LDL receptor activity, therefore decreased cholesterol uptake) \* Mild elevations in CK, AST, ALT (hypothyroid myopathy) \*\* atherosclerosis- rare in dogs but can occur with hypothyroidism

Answer 65

\*\* Do all 3 TT4, Free T4, and endogenous TSH to maximize sensitivity and specificity!! \* Serum TT4- basal level of T4 is usually low in hypothyroidism-- a normal baseline of TT4 usually excludes hypothyroidism \* Free T4- decreased in hypothyroidism (NTIS normally have normal FT4 levels) \* Endogenous TSH-- Primary would be elevated (lack of thyroid hormone removes negative feedback-- tests lack sensitivity- 25% of hypothyroid would be normal), Secondary decreased to undetectable levels, NTIS normally have normal TSH levels \*NOTE: TT4 Tests lack sensitivity and specificity-- in low numbers of hypothyroid caes, anti-T4 antibodies may cross-react with the assay (false negative); plus there are many other common non-thyroidal causes of decreased TT4 (fals positive)-- such as non-thyroidal illness syndrome, some drugs (prednisone, sulphonamides, clomipramine, carprofen, phenylbutazone), normal sight hounds have lower TT4 than other dog breeds

Answer 66

(early hypothyroidism) \* Thyroglobulin auto-antibodies (TgAA) - detected in 50% of hypothyroid dogs- leakage of Tg into circulation \*\* positive test implies THYROIDITIS-- may increase suspicion of hypothyroidism in dogs with clinical signs but equivocal TT4 levels-- antibodies may be found before the development of clinical hypothyroidism-- not all cases develop it though (may be negative with end stage disease)

Answer 67

\* CBC, Serum biochemistry profile, urinalysis, serum TT4, if TT4 is low then test free T4 (if low), endogenous TSH (and if high)--\> hypothyroidism \*\* NOTE: withdrawal corticosteroids or thyroxine for 6-8 weeks prior to testing for hypothyroidism

Answer 68

HARDIONS \* hyperparathyroidism (primary) \* Addisons (hypoadrenocorticism) \* Renal Failure (esp horses, some dogs/cats) \* Vitamin D toxicosis (plants, rodenticide) \* Idiopathic (hypercalcaemia of cats) \* Osteolysis (granulomatous disease, MM (multiple myeloma)) \* Neoplasia (humoral hypercalcaemia of malignancy) \* Spurious- lab error e.g. lipaemia, icterus, haemoconcentration, hyperproteinaemia

Answer 69

\* Impaired renal tubular response to ADH-- results in lack of aquaporin 2 water channel expression collecting ducts \* Reduced renal tubular sodium resorption- resutling in osmotic diuresis & lack of medullary concentration gradient \* Renal damage- metastatic mineralisation-- if Ca x Phos \> 70 mg/dL or \> 5.6 mmol/L

Answer 70

\* Multifactorial, decreased GFR--\> increased intestinal and renal tubular absorption, hyperproteinaemia

Answer 71

Horses- calcium retention, as the kidney eliminates large amounts of calcium in the horse (and rabbit) in health \* Dogs and cats normally have NORMAL Ca with renal failure BUT acute kidney insufficiency caused by grape/ raisin toxicity can cause hypercalcaemia --\> lab findings: Increased total calcium, increased phosphate( due to decreased GFR)-- plus azotaemia, USG isosthenuric

Answer 72

\*\* ultimately low serum Ca++ therefore increased PTH

Answer 73

An excess of vitamin D causes high blood calcium, which causes overcalcification of bones, soft tissues, heart and kidneys. \* Due to plants containing calcitiol glycosides- Cestrum, Solanum, instesinal absorption, rodenticides containing cholecalciferol, granulomatous disease e.g. balstomycosis (infection with parasitic fungi- Blastomyces dermatitidis), histoplasmosis \* Lab findings: Increased total Ca, increased phosphorous

Answer 74

\* Neoplasia-- Lymphoma, MM, thymoma, melanoma, many carcinomas ( NOT bone tumours ironically) \* Caused by tumour tissue secretion of PTHrp: induces osteoclast- mediated bone resorption, stimulates tubular resorption of calcium, decreases renal tubular phosphate resorption \* Lab findings: high total calcium, low phosphorous, high PTHrp (very labile, requires special collection), PTH low to undetectable

Answer 75

Due to decreased protein binding- normally a large portion of calcium is protein bound \* ionized calcium values remain unchanged \* In the presence of hypoalbuminaemia: a mild low TCa is unlikely to indicate a calcium disorder, a high normal TCa may indicate hypercalcaemia

Answer 76

Complexed Calcium (e.g. with phosphate, bicarbonate) + Protein Bound Calcium (albumin) + Ionized Calcium (biologically active form)

Answer 77

Uncommon endocrine disorder from iatrogenic (thyroidectomy), immune mediated destruction or decreased Mg Clinical signs: seizures, muscle tremors, rear leg cramping, restless, aggressive, hypersensitive, weight loss, inactivity \* leading to hypocalcaemia and hyperphosphataemia \* Lab findings: decreased ionized Ca, decreased PTH, increased phosphorous

Answer 78

\* Pacreatitis- calcium precipitates into soluble soaps via saponification of fatty acids (cats) \*Parturient paresis and eclampsia \* Ethylene glycol toxicity- calcium oxalate crystals form, metabolic acidosis \* Hypomagnesaemia- Magnesium is an important cofactor for PTH secretion and function- ruminants more prone \* Spurious hypocalcaemia- e.g. EDTA contamination of sample.. what else would be present if this was the case? MARKED HYPERKALAEMIA

Answer 79

\*\* cell membrane components and other roles but also used to store energy 1. Triglycerides- most common form of stored energy in mammals, derived from dietary sources or endogenous hepatic production 2. Cholesterol- the main sterol in animal tissues 3. Fatty acids

Answer 80

Because lipids are insoluble in water, they cannot be transported in aqueous solutions such as blood plasma. Therefore triglycerides and cholesterol are transported as macromolecular complexes called lipoproteins. Spherical structures consisting of a lipid core and an amphophilic outer layer of phospholipids, free cholesterol, and proteins. Fatty acids are transported bound to albumin.

Answer 81

HYdrolysis products (fatty acids and monoglycerides) are converted to triglycerides in the intestinal mucosal cells. They are then combined with phospholipids, cholesterol, and apolipoprotein to form chylomicrons which are transported to the liver and other tissues. \*\* cholesterol and triglycerides are transported as VLDL and cholesterol as LDL

Answer 82

Triglycerides are released by lipoprotein lipase- it is expressed on the endothelium in many different tissues for the uptake as free fatty acids into e.g. fat or muscle Triglycerides--\> (lipoprotein lipase)--\> free fatty acids

Answer 83

\* Hormone sensitive lipase: under sensitive regulation by hormones- fatty acids are released from stored triglycerides in fat cells by HSL (they are then transported as NEFA (non-esterified fatty acids) bound to albumin where they are taken up principally by the liver, which has a very efficient uptake process

Answer 84

\* Insulin- Promotes fat storage. Promotes esterification into triglycerides & Ups activity of lipoprotein lipase = fatty acids into adipose tissue \* Glucagon- promotes glycolysis and increase in plasma fatty acids, which have a negative feedback on glucagon \* Cortisol and ACTH- increased rate of lipolysis in adipocytes by stimulating HSL. Fat may become redistributed to the liver and abdomen, which may contribute to pot bellied appearance \* Catecholamines- adrenaline- activate HSL- energy for fight or flight \* Thyroid hormones- causing lipolysis, thyroid hormones also tend to reduce plasma cholesterol levels, via increased cell uptake of LDLs and increased cholesterol degradation

Answer 85

Adipose derived hormones \*not just a storage site for fat but also a rich source of hormone mediators (and inflammatory cytokines in obesity) 1. Leptin- informs the brain of levels of stored fat (present in serumin direct proportion to the amount of adipose tissue) 2. Adiponectin- glucose regulation and fatty acid catabolism 3. Apelin- participates in the control of blood glucose 4. Visfatin- expressed in visceral fat, serum levels correlate with obesity 4. Visfatin 5. Cytokines: Resistin; TNF alpha; IL-6. These cytokines are pro-inflammatory and may contribute to insulin resistance.

Answer 86

Dogs in cats when BW exceeds optimum by 15%. 4 or 5 out of 5

Answer 87

\* Dietary carbohydrate storage- when circulating glucose is high the body goes into storage mode. (Insulin)... when it is is low (glucagon) gets glucose out into the blood stream-- also during periods of high blood glucose, the metabolic pathways required for burning fat (e.g. lipolysis) are shut down \* Leptin resistance- never satieted as hypothalamus is less responsive \* Speying- loss of circulating sex hormones following spaying of female dogs appears to affect satiety centre in the brain and slow the metabolism \* Also high fat diets, environment, breed disposition, genetic polymorphisms

Answer 88

\* Reduced life span, osteoarthritis, exercise intolerance, tracheal collapse, hyperadrenocorticism, urethral sphincter mechanism incompetence, hypothyroidism, diabete mellitus, hyperlipidaemia, mammary neoplasia, heat intolerance, increased anaesthetic risk

Answer 89

\* As adipocytes swell with fat, the cellular changes are associated with a decreased number of insulin receptors and postreceptor failure to activate tyrosine kinase \* Also inflammatory cytokines (TNFalpha and resistin) may contribute \*\* insulin resistance in muscle and fat cells reduces glucose uptake \*\* insulin resistance in liver cells results in reduced glycogen synthesis and storage and failure to suppress glucose production and release into the blood

Answer 90

Insulin resistance and the pancreas trying to release insulin to compensate-- eventually pancreas becomes exhausted and type II diabetes mellitus may result (weight loss alone may be enough) \*\* Ponies -- Equine Metabolic Syndrome (EMS)-- insulin resistance and obesity-- grazing on high sugar content grass-- high plasma insulin levels, risk for acute laminitis--\> regional adiposity e.g. fat on nuchal crest

Answer 91

\* Hypothyroidism, DM, Hyperadrenocorticism, liver disease, protein losing nephropathy, (high fat meal) \*\* Mostly associated with insulin resistance, leading to impairment of lipoprotein lipase and hypercholesterolaemia

Answer 92

\* Negative energy balance in obese animals- metabolic rate slows to decrease consumption of glucose- glucagon secretion increases and insulin decreases-- net effect is catabolic with gluconeogenesis, glycogenolysis and peripheral lipolysis occurring--\> SHIFT towards using fatty acids as the primary energy source. LEPTIN release increases. Physiological stress from surgery or illness causes cortisol and catecholamine levels to rise, upregulating HSL activity and lipolysis. \*\* ponies and donkeys are more insulin resistant \* HSL is the rate limiting step in the breakdown of fat, if not regulated effectively then excess FFAs are released, thereofre hyperlipidaemia if the liver cannot process them via the oxidative pathway (KETONE BODY FORMATION IS NOT WELL DEVELOPED IN HORSES)--\> triglycerides in plasma overwhelms their clearance by peripheral tissues, lipidosis of other organs such as kidneys occurs = organ failure \* Can be fatal

Answer 93

Dogs- low fat diet, supplement with fish oil and omega 3 fatty acids which inhibit TG synthesis, decrease VLDL production/ secretion, and increase VLDL metabolism \* ponies and donkeys- high carbohydrate feed such as oats with high fructose corn syrup. Parenteral nutrition can be required. You are trying to correct negative energy balance here. Insulin therapy is also used, despite insulin resistance-- insulin will suppress HSL activity and activate LPL. Heparin has also been found to stimulate LPL activity and promote triglyceride use.

Answer 94

Equine Metabolic Syndrome

Answer 95

Could be from hyperlipidaemia; could be Equine Metabolic Syndrome in donkeys or ponies

Answer 96

\* The medulla of the kidney has increased Na, Cl, and urea to enable passive water resorption from renal tubules. \* Medullary washout can results from polyuria due to decrease in those solutes, therefore an inability to resorb water from the filtrate

Answer 97

\* Polyuria results from reduced renal tubular response to ADH- many causes such as pyelonephritis- endotoxin mediated, Chronic renal disease, hypercalcaemia (failure of aquaporin 2 water channel expression), hypokalaemia, hyperadrenocorticism/ glucorticoid therapy, hyperthyroidism

Answer 98

\* Blood prssure and water balance are regulated by the RAAS, hypothalamus, and pituitary gland - key regulators are renin, angiotensin, aldosterone, and ADH \* ADH promotes urine concentration via regulating water resorption in the renal collecting ducts (= increases water resorption)-- RENAL MEDULLARY MUST BE HYPERTONIC to attract the water (more than 1/3 of the nephron population must be functional) \* ADH secretion from the pituitary is stimulated via: - osmoreceptors sensing increased serum osmolality (high osmalility= need to let some of the electrolytes+ other molecules out, more water) - baroreceptors sensing reduction in blood pressure - juxtaglomerular apparatus sensing decreased blood volume- RAAS activation and generation of angiotensin II

Answer 99

\* ADH deficiency: Central Diabetes Insipidus-- pituitary disorders (rare, failure of ADH production and secretion) \* Reduced tubular response to ADH: Nephrogenic Diabetes Insipidus-- primary/ congenital (rare, failure of ADH acting on renal tubules), seconday/ acquired (common, reduced renal tubular response to ADH) \* Osmotic diuresis- increased solutes in renal filtrate (e.g. glucose or urea) \* Medullary washout- hypotonicity due to reduced interstitial Na, Cl, urea \* Primary Polydipsia: Psychogenic polydipsia (rare)

Answer 100

\* Caused by lack of ADH production & release from pituitary \* Most cases of CDI are idiopathic, but may result from: pituitary neoplasia, trauma, congenital pituitary lesion \* PU/PD is usually severe \* USG usually hyposthenuric-- if after routine diagnostics and endocrine tests still UNK consider CDI \*specialized testing: lack of response after water deprivation test; positive response after administration of exogenous ADH

Answer 101

1. Primary NDI is rare e.g. renal congenital structural or functional defect 2. Secondary (acquired) NDI is common-- PU results from reduced renal tubular response to ADH (renal insensitivity) and has many causes: Infectious diseae: pyometra, pyelonephritis, Metabolic disease: hypercalaemia (reduced medullary tonicity), hypokalaemia (reduced medullary tonicity) 3. Endocrine Disease: Hyperadrenocorticism: renal insensitivity, also inhibits ADH secretion and decreased medullary tonicity; Hyper thyroidism: same as hyperA; Chronic Kidney Disease (same as above); Iatrogenic e.g. diuretic or other drugs e.g. glucocorticoids, thyroxine, anticonvulsants

Answer 102

\* Glucosuria: DM, Fanconi's syndrome (congenital- Basenji), Primary Renal Glucosuria \* Increased Urea: Postobstructive diuresis-- renal damage

Answer 103

Any persistent polyuric condition or diuretic therapy (lack of medullary tonicity)-- due to decreased tubular resorption of solute (Na, Cl, urea) \* With Marked hypochloridemia and hyponatraemia- e.g. GIT loss \* Hypoadrenocorticism- lack of aldosterone results in sodium wasting, hypoosmolality inhibits ADH secretion from pituitary \* Hepatic failure: decreased urea production, hepatic encephalopathy may increase thirst

Answer 104

Primary polydipsia \* Compulsive water drinking - decreases ADH release from pituitary - reduces medullary tonicity \* Psychology, physiological or pathological mechanisms-- reaction to stress, fever or pain; encephalopathy/ neurologic diseae; damage to thirst centre (neoplasia, trauma) \*\* only consider if ruled all else out-- special testing: positive response after water deprivation test, lack of response to exogenous ADH

Answer 105

1. Confirm polydipsia- measuring water intake (avg. over a few days best); confirmed \> 100 ml/kg/d 2. Physical exam and history 3. Urinalysis- USG, dipstick, sediment exam, +/- UPC (urine protein: creatinine ratio) 4. CBC & biochemistry including electrolytes 5. Further testing: imaging, endocrine function tests e.g. TT4, ACTH stim/ LDDST, water deprivation test, ADH response test

Answer 106

Central Diabetes Insipidus (CDI), Nephrogenic Diabetes Insipidus- (hyperCa, hypoK, hyperA, hyperT4, pyometra, pyelonephritis), PPD (psychogenic polydipsia) and liver disease \*\* rules out CKD because kidneys are able to alter the glomerular filtrate-- isosthenuria can indicate CKD

Answer 107

1.008- 1.030/35 \* Can occur with most of the differentials: Central Diabetes Insipidus (CDI), Nephrogenic Diabetes Insipidus- (hyperCa, hypoK, hyperA, hyperT4, pyometra, pyelonephritis), PPD (psychogenic polydipsia) and liver disease \*\* CDI, PPD less likely

Answer 108

\*\* OSMOLALITY ELEVATED!!! \* USG \> 1.030/35 With confirmed PU/PD may indicate osmotic diuresis

Answer 109

\* Glucosuria (DM), proteinuria (renal disease), pyuria & culture (pyelonephritis, pyometra, UTI)

Answer 110

\* Inflammatory- Pyelonephritis, pyometra \* Lack of stress leukogram- hypoA

Answer 111

\* Hepatic disease, DM, hyperT, hyperA

Answer 112

Osmotic diuresis

Answer 113

1 Confirm PU/PD 2 Perform physical exam 3 Baseline diagnostics: Urinalysis, CBC, Biochem

Answer 114

\* Decreased tubular response to ADH (secondary NDI) \* Osmotic diuresis \* Medullary washout \* Primary PD (psychogenic) \* Primary CDI (ADH deficiency) \* Primary NDI (congenital)