Lecture 37: Parathyroid and Calcium/Phosphorus Disorders

in homeostasis, calcium and phosphorus are

inversely related

if there is decreased serum calcium, what happens?

chief cells sense the decrease and release PTH that will then act on bone, intestines, and kidneys to increase calcium

if there is increased serum calcium, what happens?

medullary c-cells produce calcitonin to decrease calcium in circulation

what is the net goal of vitamin d?

to increase serum calcium and serum phosphorus 

increased phosphorus will

inhibit vitamin D production

tissue necrosis can cause

serum phosphorus to increase

what does the mammary gland release in milk?

mainly calcium but also phosphorus

what are the 3 things that compose total calcium?

• ionized or free calcium ~50%

• protein bound calcium (80% to albumin and 20% to globulins) ~40-45%

• calcium complexed with salts ~5-10%

what is the bioactive and available form of calcium that results in hypercalcemia?

ionized calcium

hyperparathyroidism

increased calcium, decreased phosphorus

primary hyperparathyroidism 

chief cell adenoma or carcinoma → often functional tumors which produce PTH

humoral hypercalcemia of malignancy (HHM)

• increased calcium

• aka pseudo-hyperparathyroidism

• neoplastic cells produce PTHrP which has a similar homology as PTH and has same side effects of PTH

neoplasia associated with PTHrP production

• anal sac gland adenocarcinoma (AGASACA, canine)

• lymphoma

• various carcinomas

what also acts through the mechanism of PTHrP too?

schistomiasis 

hypervitaminosis D

• increased calcium and phosphorus

• supplementation with vitamin D or vitamin D rodenticides, plants → increased calcium and phosphorus absorption from gut and bone which leads to metastatic mineralization of tissues

granulomatous disease

• increased calcium and phosphorus

• acts through vitamin D mediated mechanism

• fungal disease

• pulmonary angiostrongylosis

renal insufficiency or failure in horses

acute or chronic renal diseases frequently have increased calcium and WRI or decreased phosphorus

what do healthy kidneys of equids excrete?

large amounts of calcium due to lack of vitamin D mediated absorption of calcium through gut and dietary intake

renal insufficiency or failure in dogs and cats

• most common pattern of acute or chronic renal disease is WRI to decreased calcium and increased phosphorus

• acute hypercalcemic renal failure has been reported with raisin and grape toxicosis

10-15% of dogs with chronic renal failure are

hypercalcemic

multiple myeloma 

• increased calcium

• different mechanism → causes increased binding of calcium to globulins which increases total calcium, therefore iCa2+ is expected to be WRI

hypoadrenocorticism

• increased calcium

• mechanism not well elucidated

potential effects/clinical signs of hypercalcemia

• nephrogenic diabetes insipidus

• metastatic mineralization → law of mass action

• calcium urolithiasis

• muscle tremors and weakness

• CNS signs

• GI stasis

• bradyarhythmias

law of mass action

if Ca2+ x PO4- > 70 then your patient is at risk for metastatic mineralization of the tissues

Ca2+ x PO4- > 100 =

active mineralization

first tissues to mineralize from metastatic mineralization are

• kidneys → exacerbates renal disease

• lungs

• GI tract

hypoalbuminemia 

• decreased calcium and WRI phosphorus

• most common cause of a mild hypocalcemia

hypoparathyroidism 

• decreased calcium and increased phosphorus 

• primary from a damaged parathyroid gland

• pseudo due to decreased PTH receptor sensitivity to calcium, grass tetany 

hypovitaminosis D

• decreased calcium, decreased phosphorus

• chronic renal disease

• protein losing enteropathies

• vitamin D deficiency

grass tetany

• hypomagnasemia

• decreased calcium

• occurs in ruminants grazing on lush spring pastures

• produces a functional hypoparathyroid state (decreased PTH sensitivity)

milk fever/puerperal tetany 

• eclampsia 

• decreased calcium

• calcium mobilization associated with milk production can result in hypocalcemia

• cattle → post parturient 

• small ruminants → peak lactation with multiple kids

• small breed dogs with large litters 

ethylene glycol toxicosis

• decreased calcium, increased phosphorus

• oxalates formed by metabolism of ethylene glycol bind calcium in tubules → precipitate → renal injury

acute pancreatitis

causes hypocalcemia; saponification of adipose

urinary tract obstruction 

causes hypocalcemia, MOA not understood but may be related to increased phosphorus 

renal failure

causes hypocalcemia

blister beetle toxicosis

• causes hypocalcemia

• consumption of beetles from contaminated hay bales

• MOA unknown

• occurs in horses

clinical signs associated with hypocalcemia

• muscle fasiculations

• anxiety, restlessness, or confusion

• hypersensitivity to touch

• aggression

• hyperthermia

• seizures and or tetany

• face rubbing

how do myopathies cause hyperphosphatemia

induce injury or cause necrosis of skeletal myocytes releasing PO4- from the cell into the serum

how does tumor lysis syndrome cause hyperphosphatemia?

release of phosphorus from necrotic neoplastic cells

how does acromegaly cause hyperphosphatemia?

growth hormone increases tubular (kidney) resorption of PO4-

fanconi syndrome

• hypophosphatemia

• hereditary defect reported in dogs (basenji)

• can be acquired

• causes decreased tubular resorption of glucose, amnio acids, and PO4- → often see mild glucosuria as well as proteinuria

prolonged anorexia causes hypophosphatemia in

severely starved animals

locations of magnesium in the body

• bone → 60% of body stores

• soft tissue → 38%

• extracellular fluid and blood → 1-2%

3 major fractions of magnesium in the serum

• ionized or free magnesium ~55%

• protein bound magnesium ~30%

• magnesium complexed with salts ~15%

what do you do when patients are hypercalcemic or hypocalcemic?

perform an ionized calcium

• elevations in iCa2+ → malignancy panel

• decreases in iCa2+ → treat and consider if further diagnostics are needed if persistent