Pathology of Calcium-Regulating Hormones (Jennings)

Question 1

What is the major role of the parathyroid gland?

Answer 1

Regulating serum Calcium and Phosphorus homeostasis via the production of the Parathyroid hormone (PTH)

Question 2

The parathyroid glands have an interconnected relationship with other tissues and organ systems: namely, bone, the kidneys, and the intestine. Fill in the blanks:
Parathyroid hormone acts to indirectly stimulate ________resorption and_________ matrix breakdown via osteoclasts, thereby liberating calcium stored within ____________

Answer 2

bone

Question 3

The parathyroid glands have an interconnected relationship with other tissues and organ systems: namely, bone, the kidneys, and the intestine. Fill in the blanks:
Parathyroid hormone directly stimulates calcium resorption by _____________________, as well as stimulating phosphorus secretion, thereby increasing serum calcium.

Answer 3

renal distal tubules

Question 4

The parathyroid glands have an interconnected relationship with other tissues and organ systems: namely, bone, the kidneys, and the intestine. Fill in the blanks:
Parathyroid hormone indirectly facilitates intestinal calcium absorption by inducing the production of _________________ by renal tubular epithelium. ________________ then acts on the intestinal epithelium (enterocytes) to induce the transport of calcium from the intestinal lumen into the blood.

Answer 4

vitamin D3 (1,25 hydroxycholecalciferol)

Question 5

What cells are responsible for the production and secretion of parathyroid hormone, which is stimulated by low blood calcium levels?

Answer 5

Chief cells

Question 6

What are the major players with regard to calcium-regulating hormones in the body?

Answer 6

• Parathyroid hormones (PTH)
• Calcitriol (produced in the kidney, Vitamin D)
• Calcitonin
• FGF-23 (regulation of phosphorus and plasma)

Question 7

(T/F) Calcium is utilized as a secondary messenger and at the cellular level, a lot of energy is utilized in order to maintain low levels of intracellular calcium that helps to facilitate the usage of calcium as a secondary messenger

Answer 7

True

Question 8

What are the two sources of calcium?

Answer 8

• Diet (major source)
• Bone

Question 9

(T/F) The calcium that is accessible is impacted by other things including the balance of calcium and phosphorus within the diet

Answer 9

True

Question 10

Which is the first and the most readily available and accessible source that the body can draw calcium?

Answer 10

EXtracellular fluid calcium within the bone

Question 11

What source of calcium is much less readily available and it requires osteoclasts to break down the bone in order to access it?

Answer 11

Hydroxyapatite crystals

Question 12

What is a major site of calcium regulation?

Answer 12

Kidney

Question 13

What is the function of vitamin D metabolism?

Answer 13

• Facilitates intestinal absorption of calcium (calcium-binding protein)
• Inhibits PTH synthesis and secretion by chief cells of the parathyroid

Question 14

What are a couple of different causes for Vitamin D deficiency?

Answer 14

• Diets low in vitamin D
• UV-light-induced activation of vitamin D in the epidermis
  - Sheep and South American camelids tend to be more susceptible to this than cattle

Question 15

When talking about disorders of vitamin D metabolism, they can have phosphorus deficiency. And phosphorus is required for:

Answer 15

Extracellular formation of hydroxyapatite

Question 16

What are the two major diseases of vitamin D?

Answer 16

Rickets and osteomalacia

Question 17

(T/F) Osteomalacia is more commonly seen than rickets

Answer 17

False

Question 18

Young animals at sites of endochondral ossification

Answer 18

Rickets

Question 19

Adult animals at sites of skeletal remodeling

Answer 19

Osteomalacia

Question 20

How do Rickets and Osteomalacia differ?

Answer 20

They differ in the age of onset and the age of development of these diseases

Question 21

In what species is rickets less common?

Answer 21

cats and dogs

Question 22

Consider rickets and osteomalacia, and select the answer that best fits with the following statement:

Affects growth plates

Answer 22

Rickets

Question 23

Consider rickets and osteomalacia, and select the answer that best fits with the following statement:

Caused by vitamin D deficiency

Answer 23

Both (Rickets and Osteomalacia)

Question 24

Consider rickets and osteomalacia, and select the answer that best fits with the following statement:

Associated with a failure of mineralization

Answer 24

Both (Rickets and Osteomalacia)

Question 25

Which neoplasm is MOST LIKELY to cause hypercalcemia of malignancy in dogs?

Answer 25

Apocrine gland adenocarcinoma of the anal sac

Question 26

You euthanize a severely moribund 13 year old MN domestic shorthair cat with hyperphosphatemia and severe chronic kidney disease. Renal secondary hyperparathyroidism would result in which of the following gross lesions:

Answer 26

Bilateral parathyroid hypertrophy

Question 27

What type of Hyperparathyroidism is the following? Inherent abnormality in the parathyroid gland resulting in excess PTH production

Answer 27

Primary hyperparathyroidism

Question 28

Give examples of Primary hyperparathyroidism

Answer 28

- Parathyroid nodular hyperplasia (common) - Parathyroid adenoma (common) - Parathyroid carcinoma

Question 29

What type of Hyperparathyroidism is the following? External abnormality resulting in excess PTH production

Answer 29

Secondary Hyperparathyroidism

Question 30

Give examples of Secondary Hyperparathyroidism

Answer 30

- Chronic renal disease - Dietary imbalances

Question 31

Neoplasms of the parathyroid glands Parathyroid adenomas (more common) and carcinomas (chief cell neoplasms) - Secretion of PTH results in (1) _________ hyperparathyroidism - Blood calcium is (2) ______________, hypophosphatemia

Answer 31

(1) Primary (2) increased

Question 32

You get excessive production of PTH secondary to chronic kidney disease (Renal secondary hyperparathyroidism). What is the pathogenesis?

Answer 32

CKD results in reduced GFR, which results in increased or reduced excretion of phosphate (hyperphosphatemia) with this there is an increase in the production of FGF23 and reduced calcitriol production. And this leads to signaling and feedback of chief cell hyperplasia and an increase in the production of the parathyroid (PTH) hormone

Question 33

(T/F) Reduced renal tubular epithelial cells also result in reduced 1-alpha- hydroxylase and reduced production of calcitriol

Answer 33

True

Question 34

(T/F) Cats are the most common species that we see with CKD

Answer 34

True

Question 35

What type of Secondary Hyperparathyroidism is the following describing? - Cats, dogs, non-human primates, horses, birds, and reptiles - Induced by diets with LOW calcium or HIGH phosphate with normal or low calcium - Leads to hypocalcemia -> stimulates parathyroid hyperplasia

Answer 35

Nutritional secondary hyperparathyroidism

Question 36

Tends to occur with regard to the different forms of hyperparathyroidism (nutritional secondary hyperparathyroidism >> renal > primary)

Answer 36

Fibrous osteodystrophy

Question 37

Where does the resorption of bone most severe?

Answer 37

Calvaria, Maxilla and Mandible

Question 38

What is the most common hypercalcemia secondary to neoplasia?

Answer 38

Humoral hypercalcemia of malignancy (HHM)

Question 39

Is the breakdown of bone that releases the calcium, that leads to hypercalcemia

Answer 39

Metastasis to bone

Question 40

Are localized and originate in the bone, like leukemias where plasma cell tumors can actually destroy bone and result in hypercalcemia

Answer 40

Hematologic malignancies localized to bone

Question 41

(T/F) All mechanisms of hypercalcemia secondary to neoplasia may present with similar clinical signs of hypercalcemia generally when serum calcium >4.0mmol/L

Answer 41

True

Question 42

Neoplastic cells may produce multiple humoral factors that contribute to hypercalcemia

Answer 42

HHM

Question 43

Hypercalcemia secondary to neoplasia HHM - Physiologically produced in normal animals, but elevated levels with some neoplasms resulting in hypercalcemia - Send out assays readily available to evaluate for PTHrP levels (MSU VDL) - Clinical syndrome mimics primary hyperparathyroidism

Answer 43

Parathyroid hormone-related protein (PTHrP)

Question 44

Humoral hypercalcemia of malignancy (HHM) can be associated with:

Answer 44

- Apocrine gland adenocarcinoma of the anal sac - T cell lymphoma - Multiple myeloma

Question 45

What are the mechanisms of action in PTHrP?

Answer 45

- Stimulation of osteoclastic bone resorption* - Increased calcium reabsorption from the kidney* - Increased calcium absorption from the intestine