L14: Calcium Lab Evaluation and Pathogenesis

What is the primary mechanism underlying hypercalcemia in humoral hypercalcemia of malignancy (HHM)?

Tumor-secreted PTHrP stimulates osteoclast-mediated bone resorption, increasing serum calcium.

iPTH

test to measure PTH; useful for diagnosis of primary hypo/hyperthyroidism

in what structures will PTHrP increase calcium?

• kidney and bone

• NOT THE GUT

what happens if PTHrp is increases?

PTH will decrease due to negative feedback

what is the most reliable method to evaluate calcium sttus in a hypoalbuminemic patient?

measure free ionized calcium concentration directly

what would you diagnosis in a patient with elevated total calciium, normal iCa, and decreased total proteins?

hypocalcemia is likely due to hypoalbuminemia

what is the primary effect of hypoalbuminemia on total calcium levels in veterinary patients?

it reduces the protein-bound calcium fraction

Which tumors commonly secrete PTHrP in HHM?

Anal sac adenocarcinoma, T-cell lymphoma, and squamous cell carcinoma.

in what species is hypercalcemia most common in?

dogs and horses

what values on a panel do you want to look at for hypercalcemia?

1. albumin concentration

2. total calcium

3. ionized calcium

In dogs, what is the most common cause of hypercalcemia?

1. Humoral hypercalcemia of malignancy (HHM) due to tumor PTHrP production

2. Addison’s disease

what causes hypercalcemia in horses?

1. chronic renal disease

2. high dietary calcium

In cats, what are common causes of hypercalcemia?

1. Idiopathic hypercalcemia

2. carcinoma (not lymphoma).

In cattle, what is listed as a calcium-related cause in the notes?

Iatrogenic calcium administration (milk fever).

Name the four major mechanisms that can cause hypercalcemia

1. Increased GI absorption via vitamin D

2. increased osteolysis via PTH or PTHrP;

3. decreased renal excretion (renal disease)

4. changes in protein binding that raise total Ca

what are the effects of hypercalcemia on the kidneys?

1. renal damage

2. UTI

3. nephrogenic diabetes insipidus (reduced response to ADH)

what is the effect of hypercalcemia on soft tissue?

mineralization of tisssue

what is the effect of hypercalcemia on muscle?

decreased excitability leading to weakness, constipation, and GI stasis

what is the effect of hypercalcemia on the nervous system?

decreased excitability leads to stupor, coma, and paresis

what is the effect of hypercalcemia on the heart?

rare arrhythmias and ventricular fibrillation

what are the signs of primary hyperparathyroidism?

1. hypercalcemia

2. hypophosphatemia

3. uriolithasis

primary hyperparathyroidism

PTH-secreting tumor, common in dogs

what hormone is produced in humoral hypercalcemia of malignancy?

PTHrP

what are the sources for hypervitaminosis D?

1. rodenticides

2. dietary supplements

3. toxic plants

what hormone is secreted leading to primary hyperparathyroidism?

PTH

What effect does hypoalbuminemia have on total calcium versus ionized calcium?

Total calcium decreases due to reduced protein binding; ionized calcium remains unchanged.

What is pseudohypocalcemia?

Apparent hypocalcemia caused by hypoalbuminemia; ionized calcium is normal.

In hypoalbuminemia, which calcium measurement remains reliable for physiologic Ca status?

Ionized calcium (iCa) remains reliable; total Ca can be misleading.

what is the clinical outcome of primary hyperparathyroidsim?

1. hypercalcemia

2. hypophoshatemia

3. PU/PD

4. urilithiasis

5. weakness

what is the cause of primary hyperparathyroidism?

PTH secretion autonomous secretionn from either adenoma, carcinoma, or hyperplasia

what will primary hyperparathyroidism cause in the body?

1. increased bone resorption

2. increased renal reabsorption, decreased phosphate

3. increased calcitorl

what is the cause of hypercalcemia in HHM?

tumor secretion of PTHrp from lymphoma or anal sac adenocarcinoma

what are the symptoms of hypercalcemia in HHM?

1. PU/PD

2. vomiting

3. muscle weakness

In HHM, what is the pathogenesis driven by?

Tumor production of PTHrP increases bone resorption and renal Ca reabsorption, with minimal effect on calcitriol.

What is the hormonal pattern in HHM regarding PTH?

PTH is suppressed (low or inappropriately normal) due to hypercalcemia.

How does vitamin D excess cause hypercalcemia?

Increased intestinal absorption of Ca and phosphate, increased bone resorption, and potential soft tissue mineralization.

what is the outcome from hypercalemia from vitamin D excess?

1. hypercalcemia

2. hyperphosphotemia

3. soft tissue mineralization

What is the typical HHM laboratory pattern?

Low PTH, high ionized Ca, and normal or elevated PTHrP.

What pattern is typical for vitamin D intoxication?

1. Low PTH

2. high ionized Ca

3. high 25-hydroxyvitamin D.

What pattern is typical for primary hyperparathyroidism on labs?

High ionized Ca, high PTH, and normal (or not elevated) 25-hydroxyvitamin D.

What is the pattern for HHM in terms of PTHrP and calcitriol?

Elevated PTHrP with minimal effect on calcitriol (vitamin D activation).

What is the major mechanism by which HHM leads to hypercalcemia?

PTHrP stimulates bone resorption and renal Ca reabsorption, elevating serum Ca.

what are the general mechanisms for hypocalcemia?

1. decreased absorption

2. excessive losses

3. PTH-related issues

4. protein binding

what PTH related issues are associated with hypocalcemia?

1. hypoparathyrodism

2. PTH resistance

3. pseudohypoparathyroidism

what can hypoalbuminemia often cause?

mild hypocalcemia without clinical signs

what are the specific signs of hypcalcemia in dogs?

1. muscle tremors

2. ataxia

3. seizures

4. weakness

what are the specific signs of hypcalcemia in horses?

1. tentany

2. synchronous diaphragmatic flutter

3. gait stiffness

what are the specific signs of hypcalcemia in cattle?

1. weakness

2. recumbency

hypoparathyroidism

1. low iCa

2. low iPTH

3. hyperphosphotemia

describe the pathogenesis of hypocalcemia.

1. Decreased Calcium Absorption

2. Excessive Calcium Losses

3. PTH Abnormalities

4. Protein Binding and Total Calcium

5. Miscellaneous Causes

What signs are associated with eclampsia (periparturient hypocalcemia) ?

1. PU/PD

2. vomiting

3. muscle weakness

4. lactational calcium depletion can lead to convulsions.

how does GI disease lead to hypocalcemia?

disruption of calcium absorption

how can dietary imbalances lead to hypocalcemia?

oxolates bind to calcium and inhibit its absorption

how does hypoabluminemia affect calcium?

reduces protein bound calcium but not ionized calcium

How is eclampsia best described in the lactating dog?

Lactational calcium depletion with high calcium demand leading to hypocalcemia and neuromuscular signs

What is Nutritional Secondary Hyperparathyroidism?

Imbalanced Ca:P intake causing osteolysis due to excess PTH activity.

What is Renal Secondary Hyperparathyroidism?

Vitamin D deficiency and hyperphosphatemia from renal disease causing secondary ↑PTH.

What is the typical cause of hypocalcemia in milk fever?

High Ca demand during lactation leading to lactational hypocalcemia in cows.

what would the bloodwork in a dog with eclampsia look like?

1. Low total calcium

2. low ionized calcium

3. normal phosphorus

What causes hypocalcemia in pancreatitis?

Calcium may deposit via saponification and calcitonin release can reduce calcium mobilization.

What is the role of calcitriol in calcium homeostasis?

Calcitriol (1,25-dihydroxyvitamin D) increases intestinal calcium absorption.

What is the typical phosphate status in primary hyperparathyroidism?

Hypophosphatemia (low phosphate) due to PTH-mediated phosphate excretion.

What is the typical phosphate status in HHM?

Phosphate is usually normal or variably affected; the hallmark is elevated PTHrP with low PTH.

What is the typical phosphate status in secondary hyperparathyroidism due to renal disease?

Hyperphosphatemia with low calcium and high PTH.

What laboratory change is characteristic of hypoparathyroidism?

1. Low ionized calcium (iCa)

2. low PTH

3. hyperphosphatemia.

What laboratory change is characteristic of renal disease–related hypocalcemia?

Low calcium with high phosphate and elevated PTH (secondary hyperparathyroidism).

What is the hallmark of primary hypoparathyroidism on the ionized calcium axis?

1. Low iCa

2. low PTH

3. high phosphate

What pattern of Ca and P is typical in eclampsia?

1. Low total calcium

2. low ionized calcium

3. high phosphorus

Why is ionized calcium measurement important in hypoalbuminemia?

Because ionized calcium reflects physiologic Ca status, unaffected by albumin binding.

What is the relationship between PTH and intestinal calcium absorption?

PTH increases calcitriol, which increases intestinal calcium absorption.

What happens to phosphate in primary hyperparathyroidism due to PTH effect?

Phosphate is decreased due to renal phosphate excretion (phosphaturia).

What is a key diagnostic distinction to differentiate total vs ionized calcium in veterinary patients?

Assess ionized calcium (iCa) rather than relying solely on total calcium, especially with hypoalbuminemia.

What is the role of vitamin D in calcium homeostasis?

Vitamin D increases intestinal absorption of calcium and phosphate and can contribute to hypercalcemia when excessive.

What is a key differentiator between iPTH and PTHrP in hypercalcemia workups?

PTHrP is produced by tumors in HHM and elevates Ca without increasing endogenous PTH.