PATH 2: Parathyroid Gland and Metabolic Bone Disease

Question 1

Protein-synthesizing cells that produce and mineralize bone tissue

Answer 1

Osteoblast

Question 2

An osteoblast that is embedded in bone matrix, and has lost ability to synthesize protein

Answer 2

Osteocyte

Question 3

A bone-resorptive cell, a form of macrophage

Answer 3

Osteoclast

Question 4

Functions of Bone?

Answer 4

Metabolic: Reservoir of calcium, phosphate, and other ions

Mechanical: Protection for the soft tissue organs and levers for muscle action

Hematopoietic: Host sites for bone marrow

Question 5

Two Major Hormones modulating calcium and phosphate homeostasis?

Answer 5

Parathyroid hormone (PTH)

Calcitriol (1,25 dihydroxyvitamin D)

Question 6

What regulates PTH secretrion?

Answer 6

PTH secretion is regulated by serum ionized calcium acting via calcium-sensing receptors on the surface of parathyroid cells

Question 7

Actions of PTH?

Answer 7

Bone-Enhances release of Ca+ (activates osteoclasts which produce bone resorption)

Kidney -Enhances reabsorption of Ca+ and Mg+, decreases reabsorption of phosphate

Intestine-Enhances absorption of Ca+in the intestine by increasing the conversion of vitamin D to its active form (calcitriol) in the kidney

Question 8

Process of Calcium Homeostasis

Answer 8

Question 9

Symptoms of Hypercalcemia?

Answer 9

Bones- Bone pain from bone resorption and loss

Stones- Ureteric stones from hypercalciuria

Moans- Abdominal pain, nausea, vomiting, peptic ulcer, pancreatitis

Groans-Fatigue, mild depression, memory impairment

Question 10

Causes of Hypercalcemia?

Parathyroid mediated: ___________________

Non-parathyroid mediated: _______________________

Medications ________________________

Answer 10

Parathyroid mediated: Primary Hyperparathyroidism (sporadic), Familial hyperparathyroidism, MEN syndromes

Non-parathyroid mediated- Malignancy, Vitamin D toxicity

Medications e.g. lithium, excess VitA, diuretics

Question 11

___________________________:Excessive, unregulated sporadic hypersecretion of PTH

• Leads to ________________________ w/ normal/elevated PTH
• Hyperplasia of _____________ Gland(s)
• Causes most often by _____________ (85%)
• Genetic Mutations include: __________, __________

Answer 11

Primary Hyperparathyroidism:Excessive, unregulated sporadic hypersecretion of PTH

• Leads to PERSISTENT HYPERCALCEMIA w/ normal/elevated PTH
• Hyperplasia of 1 Gland(s)
• Causes most often by Parathyroid Adenoma (85%)

Genetic Mutations include:

• Cyclin D1 Gene Inversions
• MEN-1 (Wermer syndrome) is an autosomal dominant disorder characterized by abnormalities involving the parathyroid, pancreas, and pituitary glands

Question 12

_______________________: Excessive secretion of PTH by parathyroid glands IN RESPONSE to Hypercalcemia

• Nearly always due to ____________=> compensatory hypersecretion of PTH
• Can also be caused by ___________, ___________, _________ resistance to PTH
• Hyperplasia of _____________ Gland(s)
• Excess PTH causes bone abnormalities (“____________________”)

Answer 12

Secondary Hyperparathyroidism: Excessive secretion of PTH by parathyroid glands IN RESPONSE to Hypercalcem

• Nearly always due to renal failure => compensatory hypersecretion of PTH
• Can also be caused by Vitamin D deficiency, intestinal malabsorption, skeletal resistance to PTH
• Hyperplasia of ALL 4 Glands
• Excess PTH causes bone abnormalities (“renal osteodystrophy”)

Question 13

Development of autonomous parathyroid hyperplasia due to long-standing hyperplasia secondary to renal failure leading to unchecked production of PTH?

Answer 13

Tertiary Hyperparathyroidism

Question 14

Autosomal dominant disorder associated with pheochromocytoma, medullary carcinoma of thyroid, and parathyroid hyperplasia

Answer 14

MEN 2 Mutation

Question 15

Autosomal dominant disorder characterized by abnormalities involving the parathyroid, pancreas, and pituitary glands?

Answer 15

MEN 1 Mutation (Werner Syndrome)

Question 16

Excessive secretion of PTH by parathyroid glands in response to hypercalcemia?

Answer 16

Secondary Hyperparathyroidism

Question 17

What casues renal osteodystrophy?

Answer 17

Excess PTH due to secondary Hyperparathyroidism

Question 18

What does hypoparathyroidism manifest as?

Answer 18

Acute: Tetany

Chronic: basal ganglia calcifications, cataracts, dental abnormalities, and skin change

Question 19

Cancers most often responsible for Hypercalcemia?

Answer 19

Breast Cancer
Lung Cancer
Multiple Myeloma

Question 20

Mechanisms of Hypercalcium of Malignancy?

• Tumour secretion of _____________________ or ________________
• _________ metastases with local release of cytokines
• Ectopic secretion of ___________ by tumour (rare)

Answer 20

• Tumour secretion of parathyroid hormone-related protein or 1,25-dihydroxyvitamin D (calcitriol)
• Osteolytic metastases with local release of cytokines
• Ectopic secretion of PTH by tumour (rare)

Question 21

Which condition leads to ‘Pepperpot Skull’?

Answer 21

Multiple Myeloma: clone of plasma cells being produced: marrow displaced by these myelomas=> Pepper pot appearance

Question 22

Generalized reabsorption of bone => Palor on X Ray

Cause?

Answer 22

Osteopenia

Osteoclasts stimulated by the increase PTH in Hyperparathyroidism to resorb bone

Question 23

Bone replaced by fibrous tissue, macrophages, haemorrhage and reactive woven bone?

=> Cystic degeneration (______________)

=> Hemorrhage (_____________)

Answer 23

Osteitis Fibrosa

=> Cystic degeneration (Osteitis Fibrosa Cystica)

=> Hemorrhage (Brown Tumor)

Question 24

All patients with hyperparathyroidism should have ________________checked with _________ scan

Answer 24

All patients with hyperparathyroidism should have bone mineral density (BMD) checked with DEXA scan

Question 25

How is parathyroid function checked?

Answer 25

Serum calcium and PTH levels

Question 26

What is associated with a reversal in low
BMD and hopefully a reduction in risk of fracture?

Answer 26

Parathyroidectomy