37. Parathyroid and Calcium/Phosphorus Disorders

True or false: Calcium and phosphorus are regulated by the same mediators to maintain homeostasis.

true

What are the mediators of calcium and phosphorus?

P
C
V
P

• parathyroid hormone

• calcitonin

• vitamin D

• PTH related protein

In homeostasis, how are calcium and phosphorus related? What does this mean?

inversely; if calcium increases, phosphorus decreases and vice versa

What cells sense the decreased Ca levels? What do they secrete in response to this?

chief cells; parathyroid hormone (PTH)

What organs will PTH act on?

bone, intestine, and kidney

What is the affect of PTH on bone?

causes bone resorption (osteolysis) releasing Ca and PO4 into circulation (increases serum Ca and PO4)

What is the effect of PTH on the intestines?

promotes Ca resorption from the intestinal lumen (increases serum Ca)

What is the affect of Ca on the kidney?

promotes Ca retention and encourages PO4 excretion through urine (increases serum Ca and decreases PO4)

What cells sense the increase in Ca? What do they secrete in response to this?

c-cells; calcitonin

What is the affect of calcitonin on bone?

promotes bone production so decreases serum Ca and PO4

What is the affect of calcitonin on the intestine?

decreases intestinal absorption of Ca (decreases serum Ca)

What is the affect of calcitonin on the kidney?

tells kidney to waste Ca in the urine and retain PO4 (decreases serum Ca and increases PO4)

Overall, what is the net goal of calcitonin?

decrease serum Ca levels (PO4 will increase)

What are the key signals for the kidney to transform vitamin D?

decreased Ca and increased PTH

On what organs does vitamin D have an effect?

bone and intestine

What is the effect of vitamin D on the bone?

stimulates osteolysis so increases serum Ca and PO4

What is the effect of vitamin D on the intestine?

stimulates it to resorb Ca and PO4 so increases serum Ca and PO4

What are the big inhibitors of vitamin D?

increased Ca and PO4

What does binding of insulin to GLUT 4 receptor cause?

stimulates movement of K+ and PO4 intracellularly

What effect will massive amounts of tissue necrosis have on PO4?

will cause it to increase

What will the affect of hemolysis have on PO4 levels?

increases it

During lactation, what is lost in the milk?

Ca and PO4

What three fractions compose total calcium?

I
P
C

• ionized or free calcium (~50%)

• protein bound calcium (~40-45%)

• calcium complexed with salts (~5-10%)

What percent of calcium is bound to albumin?

80%

What percent of calcium is bound to globulins?

20%

bioactive and available form of calcium which results in clinical signs of hypercalcemia

ionized calcium

How should elevations in total calcium be further investigated?

by performing an ionized calcium

What form of hyperparathyroidism is typically responsible for hypercalcemia? What is its effect?

primary hyperparathyroidism; increased Ca and decreased PO4

What is usually the main cause for the primary hyperparathyroidism? What are they often? What do they produce?

chief cell adenoma or carcinoma; functional tumors; PTH

What is humoral hypercalcemia of malignancy (HHM) also known as? What is its affect?

pseudo-hyperparathyroidism; increases Ca

What is the mechanism of action in HHM?

neoplastic cells produce PTHrP, which has a similar effect as PTH and thus has the same effects of PTH

What neoplasias are associated with PTHrP production?

A
L
V

• anal sac gland adenocarcinoma (AGASACA)

• lymphoma

• various carcinomas

What should be run in pseudo-hyperparathyroidism? What is contained in this?

malignancy profile; PTH, iCa, PTHrP

What disease acts through the mechanism of PTHrP also? What does it do?

schistosomiasis; increases Ca

What is the process of hypervitaminosis D (vitamin D toxicosis), leading to hypercalcemia?

supplementation with vitamin D or vitamin D rodenticides → increased Ca and PO4 absorption from the gut and bone (increases Ca and PO4) → metastatic mineralization of tissues (kidneys, lungs, gut)

What is the mechanism of action of granulomatous disease in causing hypercalcemia?

acts through the vitamin D mediated mechanism (causes increased Ca and PO4)

What is the main form of granulomatous disease that causes hypercalcemia?

fungal disease (blastomycosis, cryptococcosis, histoplasmosis)

What is another type of granulomatous disease that causes hypercalcemia?

pulmonary angiostrongylosis

In horses, how will acute or chronic renal diseases appear?

increased Ca levels and WRI or decreased PO4

True or false: In health, the kidneys of equids excrete large amounts of Ca due to the lack of vitamin D mediated absorption of calcium through the gut and dietary intake.

true

What is the most common pattern of acute or chronic renal disease in dogs and cats?

WRI to decreased Ca and increased PO4

Acute hypercalcemic renal failure has been reported with what toxicosis?

raisin and grape toxicosis

What percent of dogs with chronic renal failure are hypercalcemic?

10-15%

Hypercalcemia associated with multiple myeloma is a ________ mechanism

different

What is the mechanism multiple myeloma uses to cause hypercalcemia? What is the value of iCa expected to be?

causes increased binding of calcium to globulins which increases the total calcium; WRI

What is the mechanism leading to hypercalcemia caused by hypoadrenocorticism?

not well known

What are the potential effects/clinical signs of hypercalcemia?

N
M
C
M
C
G
B

• nephrogenic diabetes insipidus (polyuria)

• metastatic mineralization (law of mass action)

• calcium urolithasis

• muscle tremors and weakness

• CNS signs (depression, coma, seizures)

• GI stasis

• bradyarhythmias

According to the law of mass action, if Ca X PO4 is greater than what value is your patient at risk for metastatic mineralization of the tissues?

> 70

According to the law of mass action, if Ca X PO4 is greater than what value is your patient undergoing active mineralization?

> 100

What are the first tissues to mineralize?

K
L
G

• kidneys (exacerbates renal disease)

• lungs

• GI tract

True or false: The law of mass action is the reason as to why low phosphorus diets or phosphate binders are a component of small animal prescription renal diets.

true

What is the most common cause of mild hypocalcemia?

hypoalbuminemia

Why does hypoalbuminemia result in hypocalcemia?

albumin is one of the major proteins that bind calcium, therefore a loss of albumin results in a loss of calcium

What is the effect of hypoparathyroidism?

decreased Ca and increased PO4

What forms of hypoparathyroidism cause hypocalcemia?

P
P

• primary due to a damaged parathyroid gland

• pseudo due to decreased PTH receptor sensitivity to calcium (grass tetany)

What is the effect of hypovitaminosis D?

decreased Ca and decreased PO4

What are reasons for hypovitaminosis D?

C
P
V

• chronic renal disease

• protein losing enteropathies (PLE)

• vitamin D deficiency

occurs in ruminants grazing on lush spring pastures

hypomagnasemia (grass tetany)

What is the affect of grass tetany on calcium? How does it do this?

decreases it; produces a functional hypoparathyroid state (decreased PTH sensitivity)

What can. calcium mobilization associated with milk production result in? What is this called?

hypocalcemia; milk fever/puerperal tetany (eclampsia)

When are cattle most at risk for milk fever?

post parturient

When are small ruminants most at risk for milk fever?

peak lactation with multiple kids

What dogs are more likely to be at risk for milk fever?

small breed dogs with large litters

What is the affect of ethylene glycol toxicosis?

decreases Ca and increases PO4

What is the mechanism of action that ethylene glycol uses to cause hypocalcemia?

oxalates formed by metabolism of ethylene glycol bind calcium in the tubules → precipitates → renal injury

How does acute pancreatitis lead to hypocalcemia?

saponification of adipose

How does a urinary tract obstruction lead to hypocalcemia?

MOA not understood, but may be related to the increase in phosphorus

What is the effect blister beetles have on calcium? In what species does this occur?

causes hypocalcemia; horses

What are the clinical signs associated with hypocalcemia?

M
A
H
A
H
S
F

• muscle fasciculations

• anxiety, restlessness, or confusion

• hypersensitivity to touch

• aggression

• hyperthermia

• seizures and or tetany (ruminants will bloat)

• face rubbing

What are three causes of hyperphosphatemia?

M
T
A

• myopathies

• tumor lysis syndrome

• acromegaly

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

What are two major reasons for hypophosphatemia?

F
P

• fanconi syndrome

• prolonged anorexia

hereditary defect reported in dogs (Basenji) that can be acquired

fanconi syndrome

What is the affect of fanconi syndrome?

causes decreased tubular resorption of glucose, amino acids, and PO4

Where is most magnesium found in the body? What percent?

bone; 60% of body stores

What percent of magnesium is found in soft tissue?

38%

What percent of magnesium is found in extracellular fluid and blood (plasma and RBCs)?

1-2%

What are the three major fractions of magnesium in the serum?

I
P
M

• ionized or free magnesium

• protein bound

• magnesium complexed with salts

What percent of magnesium is ionized or free?

55%

What percent of magnesium is protein bound?

30%

What percent of magnesium is complexed with salts?

15%

What are the main causes for hypermagnesemia?

R
H
A
M

• renal insufficiency or failure (decreased GFR)

• hemolysis

• administration of MgO, Mg(OH)2 in cattle, or MgSO4 in horses

• milk fever

How does renal insufficiency or failure lead to hypermagnesemia?

decreased urinary excretion

How does hemolysis lead to hypermagnesemia?

shift of Mg from ICF to ECF

How does administration of MgO, Mg(OH)2 in cattle, or MgSO4 in horses lead to hypermagnesemia?

increased intestinal absorption of Mg

What is the main cause of hypomagnesemia?

hypoalbuminemia

What are other causes for hypomagnesemia?

P
G
E
I
K
B

• prolonged anorexia or poor feed intake (cattle)

• grass tetany (cattle or lactating mares)

• enteric disease

• increased GFR or osmotic diuresis

• ketonuria

• blister beetle (canthardin) toxicosis in horses

How does hypoalbuminemia lead to hypomagnesemia?

through hypoproteinemia

How does prolonged anorexia or poor feed intake (cattle), grass tetany (cattle or lactating mares), and enteric disease cause hypomagnesemia?

inadequate ruminal or intestinal absorption of Mg

How does increased GFR or osmotic diuresis and ketonuria cause hypomagnesemia?

excess excretion of Mg

What should be done if your patient is hypercalcemic or hypocalcemic?

perform an ionized calcium

What should be done if there are elevations in iCa?

malignancy panel (iCa, PTH, PTHrP)

What should be done if there are decreases in iCa?

treat and consider if further diagnostics are needed if persistent

What are these results showing?

hypercalcemia due to a parathyroid related state

What are these results showing?

hypercalcemia due to humoral hypercalcemia of malignancy