Pathology of Calcium-Regulating Hormones (Jennings) Flashcards
What is the major role of the parathyroid gland?
Regulating serum Calcium and Phosphorus homeostasis via the production of the Parathyroid hormone (PTH)
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 ____________
bone
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.
renal distal tubules
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.
vitamin D3 (1,25 hydroxycholecalciferol)
What cells are responsible for the production and secretion of parathyroid hormone, which is stimulated by low blood calcium levels?
Chief cells
What are the major players with regard to calcium-regulating hormones in the body?
- Parathyroid hormones (PTH)
- Calcitriol (produced in the kidney, Vitamin D)
- Calcitonin
- FGF-23 (regulation of phosphorus and plasma)
(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
True
What are the two sources of calcium?
- Diet (major source)
- Bone
(T/F) The calcium that is accessible is impacted by other things including the balance of calcium and phosphorus within the diet
True
Which is the first and the most readily available and accessible source that the body can draw calcium?
EXtracellular fluid calcium within the bone
What source of calcium is much less readily available and it requires osteoclasts to break down the bone in order to access it?
Hydroxyapatite crystals
What is a major site of calcium regulation?
Kidney
What is the function of vitamin D metabolism?
- Facilitates intestinal absorption of calcium (calcium-binding protein)
- Inhibits PTH synthesis and secretion by chief cells of the parathyroid
What are a couple of different causes for Vitamin D deficiency?
- 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
When talking about disorders of vitamin D metabolism, they can have phosphorus deficiency. And phosphorus is required for:
Extracellular formation of hydroxyapatite
What are the two major diseases of vitamin D?
Rickets and osteomalacia
(T/F) Osteomalacia is more commonly seen than rickets
False
Young animals at sites of endochondral ossification
Rickets
Adult animals at sites of skeletal remodeling
Osteomalacia
How do Rickets and Osteomalacia differ?
They differ in the age of onset and the age of development of these diseases
In what species is rickets less common?
cats and dogs
Consider rickets and osteomalacia, and select the answer that best fits with the following statement:
Affects growth plates
Rickets
Consider rickets and osteomalacia, and select the answer that best fits with the following statement:
Caused by vitamin D deficiency
Both (Rickets and Osteomalacia)
Consider rickets and osteomalacia, and select the answer that best fits with the following statement:
Associated with a failure of mineralization
Both (Rickets and Osteomalacia)
Which neoplasm is MOST LIKELY to cause hypercalcemia of malignancy in dogs?
Apocrine gland adenocarcinoma of the anal sac
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:
Bilateral parathyroid hypertrophy
What type of Hyperparathyroidism is the following?
Inherent abnormality in the parathyroid gland resulting in excess PTH production
Primary hyperparathyroidism
Give examples of Primary hyperparathyroidism
- Parathyroid nodular hyperplasia (common)
- Parathyroid adenoma (common)
- Parathyroid carcinoma
What type of Hyperparathyroidism is the following?
External abnormality resulting in excess PTH production
Secondary Hyperparathyroidism
Give examples of Secondary Hyperparathyroidism
- Chronic renal disease
- Dietary imbalances
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
(1) Primary
(2) increased
You get excessive production of PTH secondary to chronic kidney disease (Renal secondary hyperparathyroidism). What is the pathogenesis?
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
(T/F) Reduced renal tubular epithelial cells also result in reduced 1-alpha- hydroxylase and reduced production of calcitriol
True
(T/F) Cats are the most common species that we see with CKD
True
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
Nutritional secondary hyperparathyroidism
Tends to occur with regard to the different forms of hyperparathyroidism (nutritional secondary hyperparathyroidism»_space; renal > primary)
Fibrous osteodystrophy
Where does the resorption of bone most severe?
Calvaria, Maxilla and Mandible
What is the most common hypercalcemia secondary to neoplasia?
Humoral hypercalcemia of malignancy (HHM)
Is the breakdown of bone that releases the calcium, that leads to hypercalcemia
Metastasis to bone
Are localized and originate in the bone, like leukemias where plasma cell tumors can actually destroy bone and result in hypercalcemia
Hematologic malignancies localized to bone
(T/F) All mechanisms of hypercalcemia secondary to neoplasia may present with similar clinical signs of hypercalcemia generally when serum calcium >4.0mmol/L
True
Neoplastic cells may produce multiple humoral factors that contribute to hypercalcemia
HHM
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
Parathyroid hormone-related protein (PTHrP)
Humoral hypercalcemia of malignancy (HHM) can be associated with:
- Apocrine gland adenocarcinoma of the anal sac
- T cell lymphoma
- Multiple myeloma
What are the mechanisms of action in PTHrP?
- Stimulation of osteoclastic bone resorption*
- Increased calcium reabsorption from the kidney*
- Increased calcium absorption from the intestine
