Exam 4 Flashcards
Laboratory Evaluation of Thyroid Gland Disorders
- Recognize common disorders of the thyroid gland in domestic animals Click to add subtitle
Learning Objectives - Discuss laboratory tests routinely used to diagnose these disorders Date:
- Interpret test results and provide a diagnosis when possible
Adrenal Gland disorders, Hypotalamus-pituitary axis
Overview of Thyroid Function
Where is TRH made, what does it stimulate/regulate?
Where is TSH made, what does it stimulate/regulate?
What does Pituitary and Thyroid glands secrete?
What is unique to horses? Dogs?
What non-thyroidal illness lower T4? (NTI)
A. Functions
-Increase metabolic rate
-Increase Oxygen consumption
-Increase HR and contractility
-Enhance response to catecholamines
-Promote bone resorption and formation
-Increase muscle catabolism
-Increase fat catabolism
-Promote protein synthesis
-Increase Erythropoiesis
-Alter lipid protein metabolism
B. Regulation & Interference
-Hypothalamus makes Tyrotropin-Releasing-Hormone (TRH)
-TRH: stimulates the pituitary gland
-Pituitary gland makes Thyroid Stimulating Hormone (TSH)
-TSH: Stimulates the thyroid glands
-Thyroid glands make: T3 - Triiodothyronine & T4 - Thyroxine
-Tyrosine bound to thyroid peroxidase to form T3 & T4 in Colloid
**Colloid: basophilic in horses, eosinophilic others **
The thyroid is an immune-priveledge site
Autoantibodies commonly form to thyroglobulin; rarely specific to T4 or T3
-T3 = 100%
-T4 = 10-40%
In circulation they are protein bound, when unbound = Free
-Thyroid hormone binding globulin
-Transthyretin
-Albumin
-Apolipoproteins
T4-binding pre albumin in horses
Clinical status
-Free T4 correlated mostly, peripheral tissues, converts to T3
-T3 3-5x more potent than T4
-Excretion in bile and urine
Negative feedback
-Increased T3 & T4 = decreased TSH
-Horses peak early afternoon
-Dogs much lower than other species
Non-Thyroidal Illnesses & Drugs & Diets
-Inflammatory disease
-Hyperadrenocorticism
-Diabetes mellitus
-Hepatic disease
-Neoplasia
-Renal disease
-Corticosteroids (also may decrease free T4, TSH)
-Sulfonamides (may decrease free T4)
-Phenobarbital (decreases fT4)
-Carprofen
-Clomipramine (decreases fT4)
-Phenylburazone
-Equine: increase calories intake, protein, copper, zinc, Endophyte-infected fescue grass, iodine deficient (foals)
-Bovine: Leucaena leucocephala
Breeds with lower tT4
-Greyhounds
-Sighthounds
-Merino sheep
-Dutch goats (defective thyroglobulin synthesis)
C. AvailableAnalytes
Basic Canine thyroid panels
-tT4, fT4 (immulite), fT4 (equilibrium dialysis), TSH (cTSH canine specific)
Basic feline thyroid panels
-fT3, tT4, fT4 (equilibrium dialysis)
Included with some large serum biochemistry panels
-TgAA, T4AA, T3AA
fT4: usually differentiates NTI, negates effects of autoantibodies, takes longer and costs more.
- Recognize common disorders of the thyroid gland in domestic animals
HYPOTHYROIDISM
Hypothyroidism is a predominantly canine disease
Hypothyroidism
Possible etiologies
-Primary: lymphocytic thyroiditis, idiopathic thyroid atrophy, non-functional thyroid neoplasia
-Idiopathic thyroid atrophy: atrophy of functional thyroid mass over time, may be replaced with adipose tissue or fibrosis (end stage of lymphocytic thyroiditis)
Primary expected findings
-Lymphocytic thyroiditis: >50% of cases. Activates complement cascade and cell-mediated response. Autoantibodies may be detected to thyroglobulin and rarely specific to T4 or T3
-Increased TSH, decreased fT4, T4, and T3.
-Thyroid neoplasia: tumor type (90% carcinomas, 9% adenomas). 75% non-functional = hypothyroidism , 25% functional = hyperthyroidism.
Idiopathic thyroid atrophy expected findings
-Increased TSH, decreased fT4, T4, and T3.
Secondary Hypothyroidism
-Aberrant thyroid neoplasia: Imposter of T4 and T3 peripheral function, but still negative feedback to pituitary. Atrophy due to lack of TSH.
-Findings: Decreased TSH, increased fT4, fT3, T4, T3
-Pituitary neoplasia or dysfunction: replacement of thyrotropic cells and or loss of their function. Thyroid glands would atrophy due to lack of TSH stimulation.
-Findings: Decreased TSH, decreased fT4, fT3, T3, T4
Tertiary - Central Hypothyroidism
-Deficiency of TRH
-Depravation of TSH: exceedingly rare
-Glands atrophy
-Findings: decreased TRH = decreased everything
Detection of Hypothyroidism
C/S: weight gain, lathery, bilateral alopecia, mental dullness
Signalment: middle-age dogs, mid-large breeds Goldens, Dobermans, Irish setters.
Lab findings
-Increased cholesterol 75% of cases
-Increased serum triglycerides
-Mild normocytic, normochromic, non-regenerative anemia 33% of cases
-Mild to moderate increased ALP, ALT, AST
-Hypothryroxemia when 60-70% loss of functional thyroid mass
* ↓ tT4 is 90% sensitive (sn-out)
* ↓ basal tT4 may be sufficient if you rule out non-thyroidal illness (NTI) and other hypothyroxemia inducers (drugs, diet, etc)
* T4AA may cause a falsely ↑ tT4 (cross reaction)
* fT4-EDisperformedtonegateAA effect; TSH should still be ↑
- Autoantibody testing:
- Principle: determine active thyroiditis by presence of autoantibodies to:
- Thyroglobulin (common)
- T4 (rare) * T3(rare)
- Does not confirm the presence of hypothyroidism
- Can be detected prior to the clinical onset of hypothyroidism
- Confirming presence helps to suggest AA interference: ↑tT4 or ↓tT3
HYPO
HYPER
- Recognize common disorders of the thyroid gland in domestic animals
HYPERTHYROIDISM
Predominantly a Feline disease
Possible Etiologies
Primary hyperthyroidism in cats
The most common endocrinopathy in cats ~ 10% of cats >10 years old (maybe due to solely canned food diet, goitrogens)
-Thyroid adenomas + adenomatous hyperplasia: unilateral or bilateral. Contralateral gland will atrophy. Very common. Most hyperthyroid cats
-Thyroid carcinomas: rare in cats, 2% of cases
-Ectopic thyroid tissue: 3-5% of hyperthyroid cases
Findings: Negative feedback, increased T3, T4, fT4, fT3, Decreased TSH.
C/S: weight loss, polyphagia, hyperactivity, unkept appearance, PU/PD, possible aggression, tachycardia, hypertension, usually slow-onset.
Signalment: middle-age, older cats, Siamese 10x more
Routine lab findings
- Routine lab findings:
- ↑ALT(83%),ALP(58%),AST(48%)
- Erythrocytosis(53%),lymphopenia (40%), eosinopenia (34%)
- Hypersthenuria(52%)
- NTI can lower tT4 levels to WRI * Run fT4-ED, if WRI then likely NTI
- Renal failure and hyperthyroidism can mask each other in cats…
- CKD:↓tT4
- Hyperthyroidism: muscle wasting can ↓
creatinine - If you suspect both diseases and find creatinine and tT4 in the high end of the reference interval, continue testing
- ↑SDMAforrenaldisease
- ↑ fT4-ED for hyperthyroidism
Canine Hyperthryroidism
Similar signs to feline hyperthyroidism
~25% of canine thyroid carcinomas produce functional T3, T4
-Test similar to feline hyperthyroidism
-Increase tT4, if NTI also present test fT4-ED, should be Increased
- Discuss laboratory tests routinely used to diagnose these disorders Date:
Routine lab findings Feline Hyperthyroidism
- Routine lab findings:
- ↑ALT(83%),ALP(58%),AST(48%)
- Erythrocytosis(53%),lymphopenia (40%), eosinopenia (34%)
- Hypersthenuria(52%)
- NTI can lower tT4 levels to WRI * Run fT4-ED, if WRI then likely NTI
- Renal failure and hyperthyroidism can mask each other in cats…
- CKD:↓tT4
- Hyperthyroidism: muscle wasting can ↓
creatinine - If you suspect both diseases and find creatinine and tT4 in the high end of the reference interval, continue testing
- ↑SDMAforrenaldisease
- ↑ fT4-ED for hyperthyroidism
Lab findings Canine Hypothyroidism
-Increased cholesterol 75% of cases
-Increased serum triglycerides
-Mild normocytic, normochromic, non-regenerative anemia 33% of cases
-Mild to moderate increased ALP, ALT, AST
-Hypothryroxemia when 60-70% loss of functional thyroid mass
* ↓ tT4 is 90% sensitive (sn-out)
* ↓ basal tT4 may be sufficient if you rule out non-thyroidal illness (NTI) and other hypothyroxemia inducers (drugs, diet, etc)
* T4AA may cause a falsely ↑ tT4 (cross reaction)
* fT4-EDisperformedtonegateAA effect; TSH should still be ↑
- Autoantibody testing:
- Principle: determine active thyroiditis by presence of autoantibodies to:
- Thyroglobulin (common)
- T4 (rare) * T3(rare)
- Does not confirm the presence of hypothyroidism
- Can be detected prior to the clinical onset of hypothyroidism
- Confirming presence helps to suggest AA interference: ↑tT4 or ↓tT3
- Interpret test results and provide a diagnosis when possible
Disorders of the Endocrine Pancreas, Blood Glucose, and Lipids
- Discuss common disorders of blood glucose, cholesterol, and
triglycerides - Identify and interpret laboratory tests utilized to characterize those
Learning Objectives
disorders in various species
I. Glucose Metabolism & Disorders
A. Glucose Metabolism
-Gluconeogenesis: generation of glucose from non-carbohydrate sources (lactate, glycerol, some AAs)
-Glycogenolysis: the breakdown of glycogen into glucose
-Glycogenesis: synthesis of glycogen via addition of glucose to existing glycogen chains
-Glycolysis: the conversion of glucose into pyruvate for ATP generation
Glucose Homeostasis
-Decrease blood [glucose]: Insulin = promotes glycogenesis & inhibits gluconeogenesis, cortisol = promotes glycogenesis, Growth hormone = promotes glycogenesis.
-Increase blood [glucose]: Glucagon = promotes glycogenolysis and gluconeogenesis, Cortisol = promotes gluconeogenesis, inhibits insulin, Catecholamines = promote glycogenolysis, Growth hormone = inhibits insulin.
GLUT 4 glucose entry to myocytes and adipocytes Brain doesn’t not need insulin for glucose entry.
B. Hyperglycemia
Common causes MILD:
-Epinephrine: transient. Can be pronounced in cats and camelids. May be accompanied by physiological leukogram
-Prolonged physical or emotional stress: cortisol: lasts hours or longer. Stress leukogram and or elevated ALP (dogs).
-Post-prandial
Common causes MARKED:
-Type I diabetes mellitus (insulin dependent): common in dogs, rare in cats. Severe or recurrent pancreatitis, destruction of B-cells = insulin deficiency. [glucose] = >200mg/dl
-Fructosamine may be sued
-C/S: PU/PD due to osmotic diuresis. Polyphagia with weight loss. Diabetic cataracts
-Sorbitol accumulates in the lens of dogs with persistent hyperglycemia, causing osmotic swelling and disrupt lens fibers
Common causes MARKED in CATS:
-Type II diabetes mellitus (non-insulin dependent): common in cats, rare in dogs. **Characterized by insulin resistance (WRI to increased insulin) **
-Plantigrade stance diabetic neuropathy in ~10% of cats
-Dx: serum fructosamine preferred, minimizes confounding effects due to situational stress. Serial elevations in blood [glucose] >300-40 mg/dl
-C/S: PU/PU due to osmotic diuresis, polyphagia with weight loss.
Serum Fructosamine
-T1/2 = 2-3 wks
-Used to assess an average long-term glucose value - favored in cats
New Diabetics and on-going maintenance
-New Cushing’s patient urine should be culture to rule out UTI
-Rule out DKA, HHS
-Reassess or fine-tune, or change insulin type
Crisis manifestations of Diabetes Mellitus
-Diabetic ketoacidosis: ketonuria or ketonemia. Metabolic acidosis
-Hyperglycemic, hyperosmolar syndrome: severe usually >600 mg/dl. Effective osmolality usually >350 mmol/L
Miscellaneous Causes of Hyperglycemia
-Acromegaly (increased growth hormone)
-Pancreatitis, Cushing’s or exogenous steroid tx.
-Hyperthyroidism, neoplasia (glucagonoma, pheochromocytoma, pancreatic carcinoma)
-Milk fever
-Canine hepatocutaneous syndrome
-Diestrus
C. Hypoglycemia
-Marked hypoglycemia can lead to seizures, comatose state. Bells collar worn by patient to alert staff of a seizure.
Potential Causes
-Juvenile hypoglycemia: hyperemia/anorexia PEDITRIC TOY BREEDS. Lack sufficient stores for glycogenolysis (poor hepatic glycogen stores) and gluconeogenesis.
-Xylitol toxicity: stimulates profound insulin release, acute hepatic injury.
-Sepsis: Bacterial translocation as sequel of disease process. Inflammation and potential hypocalcemia, hypomagnesemia, hypocholesterolemia, and functional cholestasis.
-Insulinoma: functional pancreatic B-cell neoplasm, typically malignant. Common in ferrets and dogs
May be part of multiple endocrine neoplasm. Second most common neoplasm in ferrets, 25% die of insulenoma.
Insulin secretion and subsequent hypoglycemia may be persistent or sporadic
-Delayed Serum Separation: very common.
-Hypoadrenocorticism = decreased cortisol = insulin interference.
-Exertional hypoglacemia, glycolysis > glycogenolysis + gluconeogenesis. Hunting dogs, endurance racing horses or dogs.
-Lactational hypoglycemia: increased mammary usage.
-Pregnancy hypoglycemia/ketosis
-Insulin overdose
-Hepatic insufficiency
-Leiomyoma/myosarcoma
-Severe starvation
Lipid Metabolism and Disorders
Lipid metabolism
-Lipids are hydrophobic requiring apoprotein carriers and a phospholipid surface to prevent formation of large, obstructive lipid rafts within vasculature. Lipoprotein’s triglyceride to cholesterol ratio positively correlate with its size and negatively correlates with its density.
From large to small = less dense to most dense:
Chylomicron > VLDL > IDL > LDL > HDL
-Cholesterol: mostly produced in hepatocytes and nearly all stored in lipoproteins. Intestinal mucosa, adrenal glands, gonads also make it.
-LDL: “Leaves the liver” generally delivers hepatic cholesterol to other body cells
-HDL: “Heads to the liver” scavenges bodily cholesterol and delivers it to the liver
-Triglycerides: dietary triglycerides are packed by intestine into chylomicrons. Fasting triglycerides are mostly of hepatic origin.
-chylomicron, VLDL.
**Lipoprotein electrophoresis can fractionate the various proportions of lipoproteins; however, we mainly limit lipid assessment to evaluation of [cholesterol] and [triglycerides]
Hypercholesterolemia
-Obstructive cholestasis: obstruction in bile without hypertriglyceridemia.
-Hypothyroidism: decreased lipolysis, +/- hypertriglyceridemia.
-Diabetes mellitus: Multiple MOAs
-Nephrotic syndrome: Multiple MOAs, +/- hypertriglyceridemia
-Cushing’s disease: Multiple MOAs +/- hypertriglyceridemia
-Postprandial: frequently with hypertriglyceridemia “physiologic hyperlipidemia”
-Pancreatitis
-Briard dogs
Hypocholesterolemia
-Protein losing enteropathy
-Hemophagocytic histolytic sarcoma.
-Portosytemic shunts: ~60% of canine cases, decreased functional hepatic mass, inhibition of cholesterol synthesis by elevated bile acids.
-Hypoadrenocorticism: rare, mechanism unknown
Hypertriglyceridemia
-Equine hyperlipidemia: predisposed ponies, donkeys, miniature horses, and zebras. May result from any condition that leads to negative energy balance (anorexia, colic).
-Postprandial (after a meal)
-Pancreatitis
-Diabetes mellitus
-Idiopathic hyperlipidemia of miniature schnauzers
Non-Esterified Fatty Acids
-Used as an indicator of increased gluconeogenesis in ruminants.
-Commonly increased with: Ketosis, Hepatic lipidosis, Displaced Abomasum.
Laboratory Evaluation of Adrenal Gland Disorders
- Discuss common disorders of the adrenal gland in domestic animals Click to add subtitle
- Identify which laboratory tests should be selected for evaluation of
Learning Objectives
these disorders - Interpret and explain diagnostic test results
I. Adrenocortical Hormones
II. Hyperadrenocorticism
III. Hypoadrenocorticism
IV. Hyperaldosteronism
Adrenocortical Hormones
A. Hypothalamic-Pituitary-Adrenal Axis
Adrenal cortex is composed of three layers: GFR M (Salt, Sugar, Sex) Catecholamines
- Glomerulosa = mineralocorticoids (Aldosterone, and aldosterone synthase)
- Fasciculata = glucocorticoids (Cortisol) 17-alpha hydroxylase
- Reticularis = androgens (sex hormones) 17-alpha hydroxylase
- Adrenal medulla: Catecholamines
- Part of the sympathetic nervous system
- Produces catecholamines
** Neoplasia = pheochromocytoma**
- Hypothalamus secretes CRH (corticotropin releasing hormone)
- CRH acts on anterior pituitary to release adrenocorticotropin hormone ACTH
- ACTH acts on adrenal glands cortex to produce cortisol (stress induces it )
Negative feedback endogenous or exogenous Corticosteroids
-Inhibit CRH and ACTH
-ACTH inhibits itself
-ACTH: protein hormone like insulin. Produced as pre-pro hormone, cleavage follows. Stored in large amounts in secretory granules. Mostly circulates unbound in the blood. Act on the external cell surface of target cells. Induce immediate response via secondary messenger system **Have short half life (minutes) sustained responses only achieved through continued release. **
-ACTH action on adrenal gland cells: signal transduction moves cholesterol into mitochondria, activation of enzymatic conversion of cholesterol to PREGNENOLONE progenitor which is the progenitor of cortisol, aldosterone, testosterone, and estradiol.
-Adrenocortical hormones are steroid hormones, endocrine cells making steroid hormones store cholesterol taken up from LDLs.
Steroid Hormones
-Not stored, constantly made to order from cholesterol
-Longer half life than protein hormones
-Act on nucleus to alter transcription. Responses take a bit longer to occur (minutes to hours)
-Clearance by hepatic metabolism and renal excretion
A. Hypothalamic-Pituitary-Adrenal Axis
B. Relevant adrenocortical hormones
Glucocorticoid Effects
Catabolic except in the liver
-Catabolism of proteins and release of amino acids
-Breakdown of fat to free fatty acids
-Liver takes in metabolites for gluconeogenesis, increasing glucose output
-Liver also increases glycogen storage (glycogen accumulation, recall; rarefaction)
-Antagonizes insulin (diabetogenic)
-Reduces uptake of glucose by non-hepatic tissues
Aldosterone
-ACTH and hyponatremia are permissive of production but not primary drivers.
-Major production is directly stimulated by hyperkalemia
-Indirectly stimulated by hypovolemia or hypotension (Renin angiotensin system)
-Active in the epithelium of nephron, GI, and salivary gland
**Leads to conservation of Na, CL, and water at the expense of K and H. **
- Discuss common disorders of the adrenal gland in domestic animals Click to add subtitle
Hyperadrenocorticism
A. Overview
-Spontaneous hyperadrenocorticism: excess cortisol production by adrenal cortex. It can be pituitary dependent (PDH) or functional adrenal neoplasia (FAN)
-Iatrogenic (HAC): sustained exogenous glucocorticoids
-Cushing’s Syndrome: resulting clinical and biochemical changes related to sustained increase of glucocorticoids
-Pituitary Pars intermedia dysfunction (PPID): equine cousin of PDH, though hypercorticosolemia is not common.
B. Canine
C/S:
-PU/PD 80-90% of cases, 1st sign
-Dermatologic changes
-Abdominal enlargement, pendulous
-Lethargy, panting
-Urinary: increase incidence of UTI, struvite, calcium oxalate dihydrate.
-Cardiovascular: Hypertension 50% of cases, congestive heart failure
Insulin resistance predispose diabetes mellitus, difficult to regulate.
-Thrombosis pulmonary thromboembolism; uncommon but fatal.
-Sudden onset of dyspnea, tachypnea.
PE:
-Hepatomegaly
-Degenerative myopathy
-Most dogs not severely ill, consider other differentials if GI signs, pyrexia, or anorexia are present
Lab findings:
-SMILED: stress leukogram. Segmented Neutrophils and Monocytes Increased, Lymphocytes and Eosinophils Decreased.
-Maybe lipemic plasma, mild erythrocytosis and thrombocytosis
-ALP elevation (85% of cases)
-Hypercholesterolemia
-Maybe increased GGT & ALT
-Maybe hyperglycemia
-UA: USG < concentrated
-Maybe bacteriuria, proteinuria
-Diagnosing HAC is a stepwise process
Pituitary Dependent HAC
-85% of canine spontaneous HAC cases
-Excess ACTH secretion, neoplasia or hyperplastic pituitary, loss sensitivity to negative feedback
-Microadenomas (70%), macro adenomas (30%). May result in CNS signs
Boxers predispose Older smaller dogs, Bostons, Poodles, Terriers, Dachshunds, Beagles
-Results in Bilateral hyperplasia
Functional Adrenal Neoplasia
-15% of HAC cases
-Almost always Unilateral
-Autonomous cortisol production, without ACTH stimulation
-Negative feedback diminishes existing axis and induces atrophy of the contralateral cortex
-Large breed dogs and females mostly.
-German shepherds, Poodles, Terriers, Dachshunds, Labradors
Iatrogenic HAC
-Artificially induced due to excessive glucocorticoid therapy
-Depo-Medrol injections
-Associated with Treatment for Cushing’s disease
-Bilateral adrenocortical atrophy
-Mineralocorticoid function is preserved.
C. Feline
-Spontaneous HAC uncommon
-Most often diagnosed with insulin resistance diabetics 75-92% of cases
-PDH 80%, AT 20%, more frequent in females
-Iatrogenic HAC incidence not well studied
C/S:
-PU/PD
-Polyphagia
PE:
-Similar findings than HAC canine
-Skin fragility may be severe and wounds are large
Lab findings
-Hyperglycemia
-Stress leukogram
-Hypercholesterolemia and thrombocytosis occasionally
-LDDST
-UC:UR increased in 70-90% of cases with HAC
-ACTH stim: not recommended, even les sensitive than in dogs, detects 60% of all HAC
-Ultrasound need well-trained and good equipment
D. Equine
-PPID: pituitary pars intermediate dysfunction
-Associated with functional adenoma or hyperplasia
-Not typically with high cortisol
-Onset around 19 years old, no breed nor gender predilection
-Ponies»_space; horses
C/S:
-Hirsutism 85% of cases (excessive growth of hair)
-Laminitis
-PU/PD
-Hyperhidrosis (excessive sweating)
-Muscle wasting
-Lethargy
Lab findings
-Les reliable, less sensitive, etc than small animal.
-Fall cortisol levels are naturally higher
E. Ferret
-FAN in ferrets increases androgens rather than cortisol
-Can lead to aplastic anemia
-Function tests aimed at [cortisol] useless
-UT, UMiami tests: Estradiol, androstenedione, 17-B-OH-Progesterone. Together they detect 95% of cases.
-Estradiol alone detects 75% of cases
Pituitary dependent hyperadrenocorticism
Most common 85% of cases
- Discuss calcium, phosphorus, and magnesium regulation and common
disorders resulting in hypocalcemia or hypercalcemia
I. Calcium Background & Regulation
Roles
-Intercellular activity: neurotransmission, muscle contraction, Secretory functions
-Cell adhesion
-Coagulation: anticoagulants often calcium chelators
-Bones structure and integrity
-Free calcium is clinically relevant, hypoalbuminemia affects this
Total [Ca] = [free calcium] + [anion-bound calcium]
-Free plasma Ca = 50% biologically active form
-Anion-bound = 40-45%, 80% bound to albumin, 20% globulin
-5-10% of total Ca is bound to non-protein anions.
Mediators of Calcium homeostasis
-Parathyroid hormone (PTH)
-Vitamin D
-Calcitonin
-PTH-related protein (PTHrP)
-All circulating calcium originates from diet or bone resorption
Parathyroid Regulation of Ca
-“The brains of the Ca operation”
-Chief cells fine-tune Ca homeostasis through production of PTH, which acts to resorb and retain Ca
-PTH release directly related to [ionized Ca] it has s short half life minutes, small changes in Ca result in large fluctuations in active PTH
-PTH: stimulates Ca and Phosphorus resorption via osteocyte-osteoblast transport, digest bone. Kidney: PTH inhibits resorption of Phosphorus in the PT, stimulates 1-alpha-hydroxylase to activate Vit-D, promotes additional Ca and Mg resorption in the ascending Loop of Henle and Ca resorption in in the DT.
-Chronic neoplastic PTH production causes kidney to try and overcome PTH influence [tCa] of 12-14 mg/L, but it doesn’t fully correct hypercalcemia, nephrocalcinosis and renal damage eventually.
-Vit-D: Calcitriol is the active and most functional form of Vit-D
-primary roles: stimulates Ca and Phosphorus absorption in the intestine and bone resorption via osteoblastic cytokine release.
-Minor role: Calbindin formation so supplement Ca resorption in DT.
-Calcitonin: produced by parafollicular cells of the thyroid glands and release when [iCa] is increased
-Antagonistic to PTH: decreases osteoclastic activity, blocks renal resorption
-Synergistic to PTH: blocks renal tubular resorption of phosphorus
-Actions of PTHrP: shares 70% homology, same outcomes as PTH. Important in fetal development, irrelevant in adults.
Increased PTHrP is due to neoplasia LSA, AGASACA, and Carcinomas. Lymphocytic Squamous Adenoma, AprocrinenAnal Sac Adenocarcinomas, Lymphomas, and Squamous cell Carcinoma
- Identify diagnostic tests commonly used in the evaluation of calcium Presented by:
disorders and interpret test results
II. Disorders of Hypercalcemia
Effects of Hypercalcemia
-Polyuria due to nephrogenic diabetes insipidus (calcium interference with ADH binding)
-Renal disease secondary to mineralization: metastatic in lungs and kidney when Ca:Phos >70
-Calcium urolithiasis, UTI
-Muscle weakness: hyper polarization inhibits action potentials
-GI stasis (decreased smooth muscle excitability, Anorexia, vomiting, constipation.
-Bradyarrhythmias
-CNS changes: depression, coma, seizures
Primary Hyperparathyroidism
-Increase secretion of PTH
-Typically older animals
-Parathyroid adenoma most commonly. Less commonly hyperplasia, carcinoma.
-Uncommon in dogs, very rare in cats Keeshond dogs predisposed
-C/S: often missed by owners. Incidental detection of hypercalcemia. Mean tCa 15 mg/dl, Hypophosphatemia
**Hypercalcemia + hypophosphatemia = primary hyperparathyroidism and humoral hypercalcemia of malignancy
Diagnostic Route
If tCa > 12 mg/dl
Step 1. determine if iCa is increased
Step 2. reassess patient for lymphadenomegaly and/or an anal sac mass
Step 3. Submit to Michigan for “malignancy profile” measures tCa, PTH, PTHrP.
Steps in Fluid Evaluation
- Microbiology
- Physical Features: Color and degree of transparency, noticeable odor are recorded.
-TP or TS measured by refragtometer, microhematocrit tube, centrifugation
-Total nucleated cells count, may be automatic
-Smear Squash method two cover slips or two glass slides for identification of cell types, presence of infectious agents or neoplasia.
Common cell types found in Effusions
-Neutrophils, non-degenerative or degenerative, inflammation
-Small mononuclear cells, lymphocytes low numbers normal
-Large mononuclear cells, mesothelium or macrophages (not in the horse)
-Eosinophils rarely present
- Smear Preparation
- Protein concentration
- Cell count
