Lecture 4: Parathyroid Gland

What enzyme is responsible for the active form of vitamin D?

1 alpha-hydroxylase Stimulated by low Ca, high PTH, low PO4

What is the total amount of calcium in the body?

1000g (99% in skeleton)

What percent of plasma calcium is bound to protein (albumin)?

40%

What percentage of serum calcium is in its free or ionized form?

45-50%

What are normal levels of total plasma calcium?

8.8-10.4 mg/dL

How much of your skeleton is replaced every year as an adult? As an infant?

Adult - 18% Child - 100%

Which three organ systems are involved in calcium homeostasis?

Bone Kidney Intestine

What is injected into postmenopausal women with osteoporosis?

Calcitonin

Which values are found within a fishbone renal diagram?

Calcium (6-10) Mg (1.5 - 2.5) Phosphorus (3.5-4.5)

What happens to ionized Calcium levels when ph decreases? Increases?

Decrease pH = more free Ca Increase pH = Less free Ca

Chronic hypocalcemia can cause secondary hyperparathyroidism. How?

Decreased Ca = increased PTH = hyperplasia of parathyroid glands

Chronic hypercalcemia causes hypoparathyroidism. How?

Decreased PTH

As plasma phosphate concentration decreases, the complexed Ca2+ __________ and the ionized Ca2+ __________.

Decreases Increases

What sex hormone stimulates OPG, inhibiting osteoclasts and protecting bones

Estrogen

Which of the following can result from hyperparathyroidism? Increased bone deposition Convulsions Fractures Hypo- calcemia

Fractures

How do we treat malignant parathyroid tumors?

Furosemide, which inhibits Ca reabsorption and increases excretion Etidronate - inhibits bone reabsorption

What is the breakdown product of osteoid?

Hydroxyproline (elevated in Paget's disease)

What are consequences of hypercalcemia?

Hypophosphatemia Increased bone resorption Increased Ca reabsorption (renal) Increased Ca absorption (intestine)

What are two actions of PTH on the kidney?

Increase Ca reabsorption Inhibit phosphate reabsorption

What does parathyroid hormone do (PTH)?

Increases blood calcium

T4 and glucocorticoids ______________ bone growth

Inhibit (promote resorption)

PTH secretion is stimulated by:

Ionized calcium levels (low levels < 10 mg/dL) Mg

What is bone alkaline phosphatase (BAP)?

Is the bone-specific isoform of alkaline phosphatase. A glycoprotein that is found on the surface of osteoblasts, BAP reflects the biosynthetic activity of these bone-forming cells. BAP has been shown to be a sensitive and reliable indicator of bone metabolism.

What happens to bone when high levels of PTH are detected?

It is reabsorbed due to cytokines released from osteoblasts. Cytokines (RANK-L) stimulate osteoclasts, which reabsorb bone

What happens to calcium levels in hypoparathyroidism? Phosphate?

Low or normal. Never high Normal to high.

Increased activity of what bone cell results in increased alkaline phosphatase?

Osteoblasts

Which bone cells have PTH receptors?

Osteoblasts. Lay down new bone

What diseases feature high alkaline phosphatase?

Osteoporosis Osteomalacia Rickets Osteitis fibrosa Fracture healing Puberty Bone cancer

What is the most common bone remodeling disorder?

Osteoporosis (aggravated by loss of estrogen, and lower weight bearing stress)

What PTH analog can be secreted by malignant parathyroid hormones?

PTH-rp (PTH related peptide). Can lead to hyperparathyroidism

What causes first degree primary hyperparathyroidism?

Parathyroid adenomas (excessive PTH)

Which three hormones are involved in homeostasis of calcium?

Parathyroid hormone Calcitonin Vitamin D

Estrogen and GH _____________ bone growth

Promote

Denosumab is an osteoporosis treatment. What does it target?

RANK-L (osteoclast stimulant)

What regulates vitamin D in the body?

Renal cells. Produce 1,25-dihydroxycholecalciferol (the active metabolite) or 24,25-dihydroxycholecalciferol (the inactive metabolite) depends on the "status" of Ca2+ in the body.

In children, vitamin D deficiency causes ________

Rickets

What are symptoms of hypercalcemia?

Stones (kidney) Bones (osteitis fibrosa cystica) Grones (muscle disorders) Thrones (polyuria) Overtones (depression, anxiety)

When blood calcium levels are low, PTH stimulates ________. Urinary excretion of calcium A reduction in calcium absorption from the GI tract The activity of osteoblasts The activity of osteoclasts

The activity of osteoclasts

How many parathyroid glands are there?

four

What cancers are most commonly associated with high blood calcium?

myeloma (50% of all cases) breast cancer squamous cell lung cancer kidney cancer head and neck cancers prostate cancer

What is an osteoid?

the organic part of the matrix of bone

Where is calcitonin produced?

thyroid gland (parafollicular cells)

What is Wolff's Law?

A bone grows or remodels in response to forces or demands placed upon it. Exercise is important to bone growth

Explain why someone with a parathyroid gland tumor might develop kidney stones.

A parathyroid gland tumor can prompt hypersecretion of PTH. This can raise blood calcium levels so excessively that calcium deposits begin to accumulate throughout the body, including in the kidney tubules, where they are referred to as kidney stones.

What are some causes senile osteoporosis?

Lower dietary intake of Ca/Vit D Lower activity (loss of weight-bearing stimuli) Decreased intestinal absorption Vitamin D deficiency due to lower sunlight

What does calcitonin do?

Lowers blood calcium levels by inhibiting bone resorption

How do we treat secondary hyperparathyroidism due to renal failure?

Phosphate binders (Fosrenol)

How can chronic renal failure cause secondary hyperparathyroidism?

Renal failure = high PO4 phosphate = more bound Ca = less ion Ca = high PTH

Describe the role of negative feedback in the function of the parathyroid gland.

The production and secretion of PTH is regulated by a negative feedback loop. Low blood calcium levels initiate the production and secretion of PTH. PTH increases bone resorption, calcium absorption from the intestines, and calcium reabsorption by the kidneys. As a result, blood calcium levels begin to rise. This, in turn, inhibits the further production and secretion of PTH.

What does vitamin D do?

Tole of vitamin D is to promote mineralization of new bone, and its actions are coordinated to increase both Ca2+ and phosphate concentrations in plasma so that these elements can be deposited in new bone

What can lead to hypocalcemia, resulting in secondary hyperparathyroidism?

Vitamin D deficiency Chronic renal failure

What happens to adults with vitamin D deficiency?

Vitamin D deficiency/resistance results in osteomalacia, in which new bone fails to mineralize, resulting in bending and softening of the weight-bearing bones. Chronic renal failure

What are signs of hypocalcemia?

hyperreflexia, tetany, muscle cramps, tingling, chvostek sign and trousseau sign. All due to increased sodium permeability = increased excitability of cells