Term
| What are the three major fractions of calcium in the serum/plasma and what proportion of total calcium do they each contribute? |
|
Definition
free/ionized- 50% (this is the biologically active fraction)
protein bound- 40-45% (mostly to albumin, but also globs)
non-protein anion bound- 5-10% (citrates, PO4, lactate) |
|
|
Term
| In what species do young animals (<6months) have higher serum [Ca]? |
|
Definition
| Only dogs ~ 1-2 mg/dL > than mature dogs |
|
|
Term
| How does vitamin D facilitate calcium absorption in the intestine (mostly ileum)? What hormone augments this process? |
|
Definition
vitamin D induces mucosal epithelial cell to synthesize calcium binding proteins
This is augmented by PTH mainly by increased conversion of 25-HCC to active Vit D (1,25-DHCC) in the kidney (via 1-alpha-hydroxylase)
**vit D is required for intestinal Ca absorption in dogs, cats, and cattle. |
|
|
Term
| In what species is vitamin D not required for intestinal absorption of Ca? |
|
Definition
Horses- dietary intake contributes more to the amount of intestinal calcium absorption than vitamin D activity.
**horses also lack 1-alpha-hydroxylase so they cannot convert 25-HCC to 1,25-DHCC |
|
|
Term
| What hormones stimulate calcium release from bone? What are the mechanisms of these hormones with regard to bone and calcium? |
|
Definition
PTH- Increased bone resorption (osteoclast activation) and stimulation of calcium pumps in osteocyte membranes that promote movement of Ca out of bone into ECF
Vitamin D- Promotes osteoclast activation and enhances bone response to PTH |
|
|
Term
| What hormone blocks calcium release from bone? |
|
Definition
Calcitonin- inhibits osteoclasts, and reduces activation of osteoprogenitor cells
**with ongoing PTH stimulation osteoclasts can escape the suppressive effects of calcitonin |
|
|
Term
| T/F the majority of calcium reabsorption in the kidney is independent of PTH |
|
Definition
True- 66% of filtered calcium is passively reabsorbed in the proximal tubule (Ca-Na cotransporter)
**most protein bound calcium should not be filtered (bound to albumin and globs) |
|
|
Term
| How does PTH affect renal reabsorption of calcium? |
|
Definition
| PTH activates hormone-specific adenylate cyclase system that promotes calcium absorption in the ascending limb of the loop of henle and the distal tubule |
|
|
Term
| How does vitamin D affect renal reabsorption of calcium? |
|
Definition
Vitamin D promotes the formation of a calcium binding protein (calbindin) in the distal nephron
*this is a relatively minor contributor to renal calcium reabsorption |
|
|
Term
| How does angiotensin II stimulate renal reabsorption of calcium? |
|
Definition
Angiotensin II increases activity of NA-Ca cotransport system in proximal tubule
(main function of angiotensin II is to reabsorb sodium, in this case calcium just comes along for the ride) |
|
|
Term
| What is the Ca x PO4 product that is associated with metastatic mineralization? |
|
Definition
> 70
**occurs primarily in kidney and lung, other factors can affect the development of metastatic mineralization (e.g. presence of inhibitors to precipitation in serum, relative proportions of calcium or phosphorus) |
|
|
Term
| What anticoagulants bind calcium? |
|
Definition
|
|
Term
| Describe the methodology of the two most common total calcium assays (o-cresolphthalein, arsenazo III dye)? |
|
Definition
| Both react with calcium to form colored complexes which are then measured photometrically |
|
|
Term
| What hypercalcemic conditions are associated with increased PTH or PTHrp activity? |
|
Definition
Primary hyperparathyroidism (caused by functional parathyroid adenoma/carcinoma)
Humoral hypercalcemia of malignancy (paraendocrine (aka ectopic production of hormones- most common in carcinomas) or PTHrpr producing neoplasms (e.g. dogs- T cell LSA, AGASACA, carcinomas, melanoma; cats- carcinomas (pulmonary, thyroid), LSA; horses- myeloma)
These and other neoplasms may be associated with hypercalcemia but no concurrent increase in PTH or PTHrp, some have also been associated with increased serum [Vit D] (LSA and AGASACA in dogs)
Humoral hypercalcemia of benign disorders- (PTHrp production can associated with granulomatous lesions- these also can be a source of endogenous vitamin D) |
|
|
Term
| What is the pattern of calcium and phosphorus with increased PTH or PTHrp activity? |
|
Definition
| High calcium, low phosphorus (however, if there is concurrent decreased GFR phosphorus may be normal or increased) |
|
|
Term
| T/F [PTH] will always be increased in animals with primary hyperparathyroidism |
|
Definition
False-
Even if [PTH] is WRI, this represents inappropriate secretion of PTH in a hypercalcemic animal |
|
|
Term
| What are some sources of exogenous vitamin D? |
|
Definition
| cholecalciferol rodenticide, human psoriasis ointments, some types of plants, excessive dietary supplementation (e.g. misformulated commercial feed) |
|
|
Term
| How is granulomatous inflammation associated with increased Vitamin D production? |
|
Definition
| Macrophages produce Vitamin D (1,25-DHCC) |
|
|
Term
| What neoplasms have been associated with inappropriately high serum [Vitamin D]? |
|
Definition
LSA and AGASACA in dogs
neoplastic cells may be producing Vit D, or stimulating Vit D synthesis in other cells |
|
|
Term
| What pattern of calcium and phosphorus would be expected with increased [Vitamin D]? |
|
Definition
| Hypercalcemia and hyperphosphatemia |
|
|
Term
| What [PTH] is expected in a horse with hypercalcemic renal failure? |
|
Definition
| decreased [PTH], oddly hypophosphatemia may also be present |
|
|
Term
| What is a hypothesis for the pathogenesis of hypercalcemia in some dogs and cats with renal failure (usually associated with raisin/grape toxicosis)? |
|
Definition
Increased in non-protein anion bound calcium (e.g. calcium binds to excess citrate and PO4)
**however, most dogs and cats with renal failure of normal to low [calcium] |
|
|
Term
| What are some of the proposed mechanisms for hypercalcemia in some dogs (30%) and cats with hypoadrenocorticism? |
|
Definition
Decreased renal excretion of calcium:
-Increased Angiotensin II activity in response to
hypovolemia stimulates Na-Ca cotransporter in proximal
tubule
-Glucocorticoid deficiency |
|
|
Term
| What type of diuretic can induce hypercalcemia in dogs? |
|
Definition
| Thiazide diuretics- promote increased renal excretion of sodium and water in the distal nephron --> volume depletion enhances proximal tubular reabsorption of sodium via NA-Ca cotransporter so hypercalcemia can occur (this is quite rare) |
|
|
Term
| What is the pattern of [total calcium] and [free/ionized calcium] in cases of hypercalcemia associated with marked hyperproteinemia (secondary to multiple myeloma)? |
|
Definition
| ionized calcium begins to bind to some negatively charged globulins --> this transiently decreases ionized calcium and stimulated PTH production --> net result is increased [total calcium] and normal [free/ionized calcium] |
|
|
Term
| What pattern of calcium, phosphorus, and PTH would be expected with primary hypoparathyroidism? |
|
Definition
Decreased [calcium], decreased PTH induced bone and renal reabsoption and intestinal absorption of Ca. Hyperphosphatemia also inhibits renal formation of 1,25-DHCC (except horses) so this further contributes to hypocalcemia
Increased [phos], due to increased renal reabsorption of phos
Decreased or low normal [PTH], normal [PTH} is inappropriate in a hypocalcemic animal |
|
|
Term
| How can pseudo-hypoparathyroidism (rare) be distinguished from primary hypoparathyroidism? |
|
Definition
[PTH] is increased in animals with pseudo-hypoparathyrodism (PTH receptors or post-PTH receptor pathways are unresponsive) because parathyroid glands can respond to hypocalcemia
vs. normal or low [PTH] with primary hypoparathyroidism due to decreased ability to produce PTH |
|
|
Term
| Describe the pathogenesis of functional hypoparathyroidism associated with hypomagnesemia |
|
Definition
Mg depleted cells may be resistant to PTH and cellular responses to PTH are mediated by adenylate cyclase that require Mg
Parathyroid cells secrete less PTH
-Diminished cAMP formation (requires Mg)
-Mg and Ca engage in competitative binding to parathyroid
cells. Without Mg, more Ca can bind and inhibit PTH
secretion. |
|
|
Term
| What conditions are associated with hypovitaminosis D? |
|
Definition
Chronic renal disease in dogs, cats, cattle
-Decreased vitamin D production and concurrent
hyperphosphatemia can induce renal secondary
hyperparathyroidism
Protein losing enteropathy (dogs)- decreased intestinal absorption of vitamin D
Dietary vitamin D deficiency |
|
|
Term
| Describe the pathogenesis of hypocalcemia in animals with Vitamin-D receptor defect rickets (vitamin D dependent rickets- type II) |
|
Definition
Defective target-organ receptors --> impaired response to vit D --> decreased intestinal absorption of Ca, decreased bone and renal reabsorption of calcium --> increased [1,25-DHCC] and secondary hyperparathyroidism (increased [PTH])
* has been reported in one young cat |
|
|
Term
| Describe the pathogenesis of hypocalcemia associated with exocrine pancreatic insufficiency |
|
Definition
lipid maldigestion may reduce absorption of fat soluble vitamins including Vit D
Often concurrent hypoalbuminemia which contributes to decreased protein bound fraction of calcium |
|
|
Term
| Describe the pathogenesis of parturient hypocalcemia (milk fever) in cattle (also occurs in cats, dogs, mares and ewes) |
|
Definition
There is excessive calcium loss (milk, fetal bone development) relative to intestinal absorption --> increased [PTH] and [1,25-DHCC] however inadequate response of target cells (metabolic alkalosis can exacerbate this)
*there may be concurrent hypophosphatemia (lactation, fetal bone, decreased responsiveness of bone to PTH) <-- renal excretion of phos due to PTH may occur as well |
|
|
Term
| What is the most common cause of hypercalcitonism? what is the typical magnitude of hypocalcemia in these states and why? |
|
Definition
| functional thyroid C-cell neoplasia (aka medullary thyroid carcinoma), uncommon tumors that occur most frequently in older bulls. Exogenous calcitonin administration can also cause hypocalcemia (e.g. tx of hypervitaminosis D or humoral hypercalcemia of malignancy) Hypocalcemia is often mild because: osteoclasts are relatively refractory to calcitonin suppression in older animals AND there is a compensatory increase in [PTH] to attempt to maintain physiologic [free/ionized calcium] * if the neoplasm also destroys the parathyroid glands hypocalcemia can be marked because of concurrent PTH deficiency |
|
|
Term
| Describe the pathogenesis of nutritional secondary hyperparathyroidism |
|
Definition
vitamin D deficient diet or low Ca:Phos ratio (e.g. meat only diet) -> dietary hypocalcemia stimulated parathyroid gland hyperplasia -> increased PTH secretion maintains [free/ionized Ca] but causes osteomalacia
also increased renal excretion of phosphorus is present (due to phosphaturic actions of PTH and often concurrent high dietary intake) |
|
|
Term
| What type of plant can impair intestinal calcium absorption in horses in cattle resulting in hypocalcemia? |
|
Definition
high oxalate but low calcium containing plants
*alfalfa has high oxalate but is also high in calcium so not associated with hypocalcemia |
|
|
Term
| What conditions are associated with hypocalcemia due to excessive urinary excretion of calcium? |
|
Definition
Ethylene glycol (oxalates and other products of ethylene glycol metabolism bind calcium in tubular fluid and induce calciuria, also associated with acute nephrosis and decreased tubular reabsorption of calcium)
Metabolic alkalosis (increased renal excretion of bicarbonate obligate concurrent renal loss of cations including Ca+2) <-- metabolic alkalosis also reduces target cell responsiveness to PTH in cattle with milk fever exacerbating hypocalcemia |
|
|
Term
| What antibiotic, when given rapidly IV can bind [free/ionized Ca]? |
|
Definition
| tetracycline, although there may be a decrease in [free/ionized Ca], [total Ca] is usually WRI |
|
|
Term
| Acute pancreatitis can be associated with hypocalcemia in dog and cats, but it's most common in which one? |
|
Definition
Cats, associated with a poorer prognosis
*usually [free Ca] is decreased, [total Ca] may be decreased or normal |
|
|
Term
| What are some proposed mechanisms for hypocalcemia in acute pancreatitis? |
|
Definition
| abnormal hormonal regulation (glucagon, calcitonin, PTH), binding of free calcium to plasma fatty acids, extravasation of protein bound-Ca due to increased vascular permeability |
|
|
Term
| What is the proposed mechanism for hypocalcemia secondary to urinary tract obstruction? |
|
Definition
typically mild to moderate, may be related to increased binding of free calcium to inorganic phosphorus as well as impaired renal reabsorption of calcium as a result of tubular injury
** decreases in [fCa] may be greater than [tCa] |
|
|
Term
| What is the proposed pathogenesis of hypocalcemia that is observed in some animals (dogs and cats) with acute renal failure? |
|
Definition
Rapid onset hyperphosphatemia may result in formation of Ca/Phos complexes, also decreased tubular reabsorption of calcium
**other concurrent pathologic states may also contribute to hypocalcemia including ethylene glycol toxicity, hypoalbuminemia, and acute pancreatitis |
|
|
Term
| How can sweating in horses contribute to hypocalcemia? |
|
Definition
| significant chloride loss in sweat can induce a hypochloremic alkalemia --> increased calcium binding to albumin There can also be direct loss of calcium in the sweat |
|
|
Term
| T/F hypocalcemia is often observed in horses with myopathies |
|
Definition
true
mechanism is unknown and may be multifactorial (decreased intake, increased renal loss, intracellular translocation of Ca+2 into damaged myocytes, profuse sweating [hypochloremic alkalosis promotes increased albumin-Ca binding]) |
|
|
Term
| Describe the pathogenesis of hypocalcemia associated with acute tumor lysis syndrome |
|
Definition
PO4 is released from lysed cells that complexes with Ca in tissues
PO4 and lactate from lysed/hypoxic cells may also complex with Ca in tubular fluid and inhibit renal reabsorption of Ca |
|
|
Term
| Describe the pathogenesis of hypocalcemia associated with rumen overload |
|
Definition
| ingestion of large amounts of fermentable CHO --> acute lactic acidosis, hypovolemia, azotemia, hyperphosphatemia -> Ca can bind to phosphorus and lactate and deposit in tissue, can also complex in tubular fluid resulting in impaired renal reabsorption of Ca |
|
|
Term
| Why should samples collected to measure [free/ionized calcium] be processed anaerobically? |
|
Definition
| To reduce changes in pH caused by loss of CO2 into the air (this would raise the pH and decreased [fCa]) |
|
|
Term
| How does pH of a sample affect measurement of [fCa]? |
|
Definition
Raising the pH decreases [fCa], lowering the pH increases [fCa]
Albumin binds many positively charged ions so if there is more H+ (e.g. lower pH), the H+ outcompetes the Ca+ for protein binding resulting in a higher [fCa], if there are less H+ (e.g. higher pH) then more Ca binds to albumin resulting in a lower [fCa]
**keep in mind that concurrent organic acidosis can bind [fCa] and lower it, and that [PTH] can be increased in response to acidosis as well |
|
|
Term
| What is the only acceptable anti-coagulant for measuring [fCa] in plasma or whole blood? |
|
Definition
Heparin (heparin can bind Ca so care must be made to use either calcium titrated heparin tubes (need special reference intervals to account for added Ca) or make sure that the heparin concentration of the sample is < 15 U/ml blood)
*can also measure it in serum (most stable in serum), but serum separator tubes should not be used because the gel contains calcium |
|
|
Term
| Describe the methodology typically used to measure [fCa] |
|
Definition
ion-selective electrodes via potentiometry
**often also contain a pH electrode and may report a calculated [fCa] expected if the sample had a pH of 7.4 |
|
|
Term
| What is the pattern of [fCa] and [TCa] in some cats with hyperthyroidism? |
|
Definition
decreased [fCa], normal [tCa]
*pathogenesis is not clear |
|
|
Term
| How does pH affect [PTH]? |
|
Definition
Metabolic or respiratory acidosis with constant [fCa]- increased [PTH]
Metabolic or respiratory alkalosis with constant [fCa]- decreased [PTH] |
|
|
Term
| How does PTH contribute to maintenance of acid-base status? |
|
Definition
| PO4 released from bone acts as a buffer in blood PO4 participates in renal excretion of H+ in the proximal tubule and reduces renal excretion of HCO3- |
|
|
Term
| T/F most hypercalcemic samples have increased [fCa] |
|
Definition
True-
increased PTH, PTHrp, and Vitamin D all increase [fCa] |
|
|
Term
| T/F excess heparin can falsely decrease [fCa] |
|
Definition
True
Some fCa will bind to heparin |
|
|
Term
| What is the predominant form of phosphorus in the blood at a normal pH (7.4)? |
|
Definition
HPO4-, and to a lesser extent H2PO4- (4:1)
**but measured phosphorus is reported in terms of inorganic phosrophus (Pi) |
|
|
Term
| T/F the majority of phosphorus in the blood is free/ionized |
|
Definition
True- 55% is free
35% bound to non-protein cations, 10% protein bound |
|
|
Term
| What factors promote increased conversion of 25-HCC to 1,25-DHCC (via alpha-1-hydroxylase) in the kidney? |
|
Definition
|
|
Term
| What factors inhibit increased conversion of 25-HCC to 1,25-DHCC (via alpha-1-hydroxylase) in the kidney? |
|
Definition
| high [fCa] and high [PO4] |
|
|
Term
| What factors are associated with decreased renal excretion of PO4? |
|
Definition
| decreased GFR, decreased PTH, increased growth hormone |
|
|
Term
| What hormone promotes phosphorus intake by cells? |
|
Definition
Insulin
**this is because once glucose enters the cell is becomes phosphorylated to enter glycolytic or glycogen synthesis pathways. Utilization of intracellular PO4 shifts the concentration gradient such that PO4 in the ECF moves passively into the cell |
|
|
Term
| What pre analytical factors can erroneously increase serum [PO4]? |
|
Definition
| in vitro hemolysis and delayed removal of serum or plasma from packed RBC |
|
|
Term
| How does PTH promote renal excretion of PO4? |
|
Definition
| PTH acts through a cyclic adenosine monophosphate messenger system to inhibit cotransport of Na and Phos in the distal tubule |
|
|
Term
| What is the main mechanism for increased [PO4] in young growing animals? |
|
Definition
Growth hormone - increases tubular reabsorption of Phos
**up to 2x adult URI in puppies, less dramatically increased (x0.5 URI) in kittens. The also have corresponding increased [ALP] compared with adults. Metastatic mineralization is uncommon in young animals despite increased CaxPhos product |
|
|
Term
| Describe the most common methodology for measuring serum PO4 |
|
Definition
PO4 reacts with ammonium molybdate to form a colored complex measured by photometry
* because ammonium molybdate is an acid, it can cause immunoglobulin to precipitate producing turbidity that can falsely increased [PO4]. Bilirubin can also affect various assays (both positive and negative interference |
|
|
Term
| What conditions result in hyperphosphatemia due to decreased renal excretion of PO4? |
|
Definition
Decreased GFR (pre, renal, post) **magnitude of increased [PO4] tends to parallel degree of azotemia except in horses
Decreased [PTH] or impaired PTH function (primary hypoparathyroidism- impaired PTH receptors or unresponsive post-PTH receptor pathways)
Acromegally (increased growth hormone impairs renal tubular PO4 reabsorption |
|
|
Term
| What conditions result in hyperphosphatemia due to increased intestinal absorption of PO4? |
|
Definition
Increased intake of PO4: phosphate enema or ingestion of phosphate urinary acidifier, diets with low Ca:PO4 ratio
increased vitamin D
Devitalized intestinal lesions (leakage of intracellular PO4) |
|
|
Term
| What conditions result in hyperphosphatemia due to shift of PO4 from ICF to ECF? |
|
Definition
Myopathies
Acute tumor lysis syndrome |
|
|
Term
| What are some proposed mechanisms for hyperphosphatemia in hyperthyroid cats? |
|
Definition
| Thyroxine may promote osteoclast activity releasing Ca and PO4 from bone. |
|
|
Term
| What three conditions have been associated with hyperphosphatemia but the mechanism is not entirely clear? |
|
Definition
Hyperthyroidism in cats
Lactic acidosis
Hyperadrenocorticism in dogs |
|
|
Term
| What conditions can be associated with pseudohyperphosphatemia? |
|
Definition
| in vitro hemolysis, hyperbilirubinemia, monoclonal gammopathy |
|
|
Term
| What disorder can be associated with hypophosphatemia and hyperphosphaturia? |
|
Definition
Fanconi syndrome- defect in proximal tubular reabsorption of glucose, amino acids, and phos
*can be inherited or acquired, not all affected individuals will develop hypophosphatemia and hyperphosphaturia |
|
|
Term
| What conditions are associated with hypophosphatemia due to impaired intestinal absorption of Phos? |
|
Definition
prolonged anorxia or PO4 deficient diet
PO4 binding agents
hypovitaminosis D
intestinal malabsorption |
|
|
Term
| What three conditions are associated with hypophosphatemia due to shift from ECF to ICF? |
|
Definition
Hyperinsulinism (endogenous -e.g. insulin secreting tumor, physiologic response to glucose infusion or exogenous) due to phosphoylation of glucose for metabolism
Glucose infusion can further exacerbate hypophosphatemia due to osmotic diuresis --> increased flow rate through nephrons impaired PO4 reabsorption
Respiratory alkalosis: alkalemia stimulates phosphofructokinase activity (rate limiting step in glycolysis) --> increased phosphorylation promotes entry of PO4 into the cell |
|
|
Term
| What conditions are associated with hypophosphatemia due to unadequate mobilization of PO4 from bone? |
|
Definition
| Milk fever (postpaturient paresis) in cattle and eclampsia in bitches- cannot mobilize sufficient Ca and PO4 from bone to replace Ca and PO4 lost in milk |
|
|
Term
| What are 4 conditions sometimes associated with hypophosphatemia in horses, though unknown mechanisms? |
|
Definition
Renal failure
Halothane anesthesia
colic*
cantharidin (blister beetle) toxicity*
*may be associated with loss of protein bound Ca in the GI |
|
|
Term
| What can cause pseudohypophosphatemia? |
|
Definition
the presence of unconjugated bilirubin
*only in some assays |
|
|
Term
| What are the three major fractions of magnesium in the serum/plasma and what proportion of total magnesium do they each contribute? |
|
Definition
All Mg is IONIZED, most of which (55%) is free Mg and like calcium this is the fraction that is biologically active.
30% is bound to negatively charged proteins
15% is bound to nonprotein anions (e.g. citrate, PO4) |
|
|
Term
| In which species is [tMg} in erythrocytes equal to [tMg] in plasma or serum? |
|
Definition
|
|
Term
| In ruminants how is dietary Mg absorbed? |
|
Definition
| Mg is absorbed in the rumen (and possibly also the small intestine) in a process linked to Na-K adenosine triphosphatase |
|
|
Term
| In monogastrics where is dietary Mg absorbed and what factors influence the degree of absorption? |
|
Definition
distal small intestine and colon
Mg absorption is enhanced by Vitamin D and inhibited by high dietary Ca or PO4 |
|
|
Term
| Why might you measure Mg in cow urine? |
|
Definition
r/o hypomagnesemic tetany (grass tetany)
Mg is expected to be reabsorbed from renal tubular fluid if there is hypomagnesemia. The presence of Mg in the urine indicates that the transport maximum in the renal tubule has been exceeded |
|
|
Term
| What are potential routes of Mg excretion? |
|
Definition
Feces (excess dietary intake)
Kidney (Mg is reabsorbed unless the amount filtered exceeds resorptive capacity, also increased flow rate (e.g. osmotic diuresis, loop diuretic) promote renal excretion of Mg
Milk (5x more [Mg] in milk compared to serum) |
|
|
Term
| What hormones stimulate Mg reabsorption in the ascending limb of the loop of henle? |
|
Definition
| ADH, PTH, glucogone, calcitonin, beta adrenergic agonists |
|
|
Term
| How does PTH affect serum [Mg]? |
|
Definition
| PTH increases serum [Mg] by increasing renal reabsorption, mobilization from bone, and intestinal absorption |
|
|
Term
| How does administration of 1,25-DHCC affect serum [Mg]? |
|
Definition
| 1,25-DHCC decreases serum [Mg], possibly because it also downregulated PTH |
|
|
Term
| What substances/hormones are associated with decreased serum [Mg]? |
|
Definition
1,25- DHCC (down regulation of PTH)
Thyroxine and Aldosterone (increased renal and fecal excretion)
*aldosterone deficiency can be associated with increased [Mg] |
|
|
Term
| Describe the methedology of most assays that measure serum [Mg] |
|
Definition
| Metallochromic indicators or dyes change color when they selectively bind Mg. Atomic absorption spectrometry is the reference method but not used in most clinical labs. Other methods include ion selective electrodes and equilibrium dialysis |
|
|
Term
| In what fluid is [Mg] more stable than serum or plasma, esp. antemortem |
|
Definition
vitreous humor (up to 48h post mortem) and aqueous humor (up to 24h post)
**mostly useful for postmortem diagnosis of grass tetany because release of Mg from cells during following death can falsely increase postmortem plasma [Mg] |
|
|
Term
| Describe the proposed mechanism for hypermagnesemia in cattle with milk fever |
|
Definition
| Increased [PTH] may enhance renal reabsorption of Mg |
|
|
Term
| Increased [PTH] and hypermagnesemia are seen in what two conditions in cattle? |
|
Definition
Milk fever
transiently postpartum |
|
|
Term
| What are some factors that may contribute to the hypomagnesemia observed in cattle with grass tetany |
|
Definition
lush grass diet is high in K+ and low in Mg
aldosterone may play a role |
|
|
Term
| In what species are enteric diseases associated with hypomagnesemia? |
|
Definition
dogs (decreased intestinal absorption +/- concurrent hypoproteinemia and decreased protein bound Mg component)
Horses (decreased feed intake and decreased intestinal absorption) |
|
|
Term
| What conditions are associated with excessive renal loss of Mg? |
|
Definition
osmotic diuresis
Ketonuria (Mg forms complexes with beta-hydroxybutyrate and acetoacetat resulting in decreased tubular reabsorption) |
|
|
Term
| How does blister beetle poisoning in horses affect serum [Ca] and [Mg]? |
|
Definition
|
|
Term
| In what species is endotoxemia associated with hypomagnesemia |
|
Definition
horses
due to intracellular shifting of Mg possibly mediated by ADH or insulin |
|
|
Term
| What organs inactivate or degrade PTH? |
|
Definition
|
|
Term
| What is the primary mediator of PTH secretion? |
|
Definition
Ca participates in a negative feedback loop:
fCa binds to parathyroid gland chief cell calcium-sensing receptors --> initiates a series of signaling pathways that culminate in inhibition of PTH secretion |
|
|
Term
| How can Mg affect PTH secretion? |
|
Definition
Mg can interfere with fCa binding to parathyroid gland chief cell calcium-sensing receptor (CaSR) facilitating PTH secretion
Thus hypomagnesemia may inhibit PTH secretion even at lower [fCa] |
|
|
Term
| How does acidosis affect PTH secretion? |
|
Definition
Acidosis stimulates PTH secretion (although in metabolic acidosis increased [fCa] can be sufficient to inhibit PTH secretion)
** in acidosis H+ binds more to proteins and displaces Ca resulting in increased [fCa], keeping in mind that in organic acidosis (e.g. lactate, ketones) the organic anions can also bind Ca lowering [fCa]** |
|
|
Term
| How does alkalosis (metabolic or respiratory) affect [PTH] |
|
Definition
| alkalosis inhibits PTH secretion |
|
|
Term
| What is the methodology typically used to measure serum [iPTH] |
|
Definition
RIA (developed for humans but sufficient species cross-reactivity to be valid in domestic animals)
iPTH (immunoreactive PTH) is named such because the assay reacts with PTH, pro-PTH, pre-pro-PTH and/or fragments of PTH. |
|
|
Term
| How should a sample intended for measurement of [iPTH] or [PTHrp] be prepared? |
|
Definition
with protease inhibitors
*frozen serum or plasma without protease inhibitors may be stable if frozen *[iPTH] only* |
|
|
Term
| What endocrinopathy other than primary hyperparathyroidism is associated with increased [iPTH]? |
|
Definition
| Hyperadrenocorticism **these animal were norocalcemic |
|
|
Term
| What conditions are associated with decreased [iPTH] due to inhibition of PTH secretion? |
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Definition
hypervitaminosis D
Hypercalcemic disorders with increased [fCa] (except primary hyperparathyroidism)
Mg depletion (Mg interferes with fCA binding of parathyroid CaSR, which is normally an inhibitor of PTH secretion, so less Mg = more FCa binding = decreased PTH secretion) |
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Term
| What is PTHrp's physiologic function? |
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Definition
regulates Ca balance in the fetus, modulates cartilage and bone development. At birth control of Ca switches to PTH.
*PTHrp is produced by many adult cells, but serum levels are very low in healthy adults |
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Term
| T/F increased PTHrp is only seen in association with neoplasia |
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Definition
False, there are rare reports of increased [PTHrp] in dogs with granulomatous disease*
*heterobilharzia americana |
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Term
| What enzyme in hepatocytes catalyzes the formation of 25-HCC from cholecalciferol? |
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Definition
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Term
| What receptors on proximal renal tubular epithelial cells are responsible for receptor mediated update of 25-HCC and vitamin D binding proteins that pass through the glomerular filtration barrier? |
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Definition
Megalin, amnionless, and cubulin
**these receptors also facilitate update of cobalamin/intrinsic factor in the intestine |
|
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Term
| What is the major factor that contributes to the formation of 1,25-DHCC (aka calcitriol)? |
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Definition
| [Ca], high [Ca] is inhibits 1,2-DHCC and vice versa |
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Term
| What shared mechanism is associated with increased Ca absorption or resorption from the intestine and kidney, respectively? |
|
Definition
| Increased formation of the calcium binding protein (calbindin) |
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Term
| How does vitamin D affect PTH concentrations? |
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Definition
| Increased vitamin D inhibits PTH by inhibiting transcription of PTH mRNA in parathyroid glands |
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Term
| What are the two main assays that can be used to quantify [1,25-DHCC]? |
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Definition
radioreceptor assay and RIA
**sample must be deproteinized or extracted to free vit D metabolites because nearly all vit D in serum is protein bound (mostly by alpha globulins and albumin) |
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Term
| What type of rickets is associated with increased serum [1,25-DHCC]? |
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Definition
Vitamin D-dependent rickets, type II
*vit D receptor defect |
|
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Term
| How does increased [PTH] promote increased [1,25-DHCC]? |
|
Definition
| activation of renal alpha-1-hydroxylase |
|
|
Term
| What cells synthesize calcitonin? |
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Definition
|
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Term
| What substances stimulate thyroid C cells to produce calcitonin? |
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Definition
| increased [fCa], [fMg], alpha and beta adrenergic hormones, gastrin, and cholecystokinin |
|
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Term
| What substances inhibit calcitonin secretion by thyroid C cells? |
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Definition
| low [fCa] and increased [somatostatin] |
|
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Term
| What are the net effects of calcitonin activity? |
|
Definition
| decreased [fCa], [tCa] and [Pi] by inhibiting osteoclast resorption of bone and inhibiting renal tubular reabsorption of Ca and PO4 |
|
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Term
| What is the major method for measuring [calcitonin]? |
|
Definition
RIA
**marked species differences in amino acid sequence limit cross reactivity of Ab, there is an assay for canine calcitonin |
|
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Term
| What disorders are associated with increased [icalcitonin]? |
|
Definition
Medullary thyroid carcinoma (i.e. C cells)
some non-thyroid neoplasia, especially if derived from neutral crest tissue |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D in canine hypoadrenocorticism? |
|
Definition
increased Ca (decreased renal excretion of Ca)
WRI to increased PO4
decreased to WRI PTH
WRI PTHrp
WRI Vit D |
|
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Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D in hypercalcemic renal failure? |
|
Definition
increased [Ca]
WRI to decreased [PO4]
WRI to decreased (only horses) [PTH]
WRI [PTHrp]
unknown [vit D] |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D in chronic renal failure? |
|
Definition
WRI to decreased [Ca]
Increased [PO4]
Increased [PTH]
WRI [PTHrp]
Decreased to WRI [vit D] |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D in vitamin D receptor defect rickets? |
|
Definition
decreased [Ca]
decreased [PO4]
increased [PTH]
WRI [PTHrp]
increased [vit D] |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D in milk fever? |
|
Definition
decreased [Ca]
decreased [PO4]
WRI to Increased [PTH]
WRI [PTHrp]
WRI to increased [vit D] |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D with prolonged anorexia? |
|
Definition
WRI [Ca]
decreased [PO4]
WRI [PTH]
WRI [PTHr[]
WRI [vit D] |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D with vitamin D toxicosis? |
|
Definition
| increased [Ca] WRI to increased [PO4] decreased to WRI [PTH] WRI [PTHrp] increased [Vit D] |
|
|
Term
| What is the expected pattern of Ca, PO4, PTH, PTHrp, and Vit D in humoral hypercalcemia of malignancy? |
|
Definition
increased [Ca]
decreased [PO4]
Decreased to WRI [PTH]
increased [PTHrp]
WRI [Vit D] |
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