Calcium and the Parathyroid gland Flashcards

Question

what are osteoblasts?

Answer 1

Bone forming cells - produce the components of the matrix & aid in calcification Often appear in groups Originate from mesenchymal stem cells (bone marrow stem cells) or connective tissue mesenchymal cells. There are classical markers that identify osteoblast activity Elevated levels of Alkaline phosphatase and osteocalcin show that new bone has been synthesised

Answer 2

bone resorbing cells - promote the release of calcium from bone found within the Howship’s lacunae (pit), in contact with the calcified bone surface Produce acid (to resorb minerals) & enzymes (to resorb matrix) Classical markers that identify them: Carbonic anhydrase, tartrate-resistant acid phosphatase (TRAP), RANK, Calcitonin receptor - indicate degree of bone resorption Multinucleated & originate from bone marrow lineage Attach to bone via integrins

Answer 3

1. Osteoclast precursor starts of as a single nucleate cell. 2. Osteoclast precursors use their rank receptor to interact with osteoblasts to produce a mature osteoclast. 3. RANK receptors on the surface of mature osteoclasts have become a major target to supress bone resorption. 4. OPG (naturally occurring inhibitor) is released in general physiology to block rank function and prevent further osteoclast development. 5. Drugs have been developed to synthetically inhibit rank function as well e.g. Denosumab.

Answer 4

1. Resting Phase: Osteocytes (star shape) send signals necessary for bone formation or bone resorption. They communicate with the osteoblast cells (above) and osteoclasts. 2. Osteoblasts move off and osteoclasts come and cause bone resorption, producing pits - Howship’s Lacuna 3. Reversal phase: Osteoclasts leave pits and the surface is replaced by osteoblast to rebuild the bone - put down layers of collagen, mineralising with hydroxyapatite crystals until the bone is full restored. (another pic on hamzahs notes)

Answer 5

Raised serum PTH Primary Hyperparathyroidism: Parathyroid tumour in one of the glands (usually benign adenoma) Causes excess secretion of PTH Causes hypercalcaemia and low serum phosphate due to high reabsorption of calcium and high phosphate excretion occurring at the kidney higher production of 1,25D3 causes higher absorption of calcium from intestines elevated bone resorption loss of -ve feedback control - does not respond to high serum calcium level and high 1,25D3 treatment: Surgery - removal of the one parathyroid gland

Answer 6

"stones, bones, abdominal groans, thrones and psychiatric overtones" Cardiac: hypertension Renal: polydipsia, polyuria, renal stones Rheumatoid: joint pain, fractures, osteitis GI: constipation, pancreatitis Neuro: lethargy/confusion, depression

Answer 7

Renal disease (kidney dysfunction) increased phosphate absorption - hyperphosphatemia Decreased calcium absorption - Hypocalcaemia Decreased activation of vit D3 Lack of negative feed-back: You get increased PTH secretion due to decreased levels of 1,25D3 and hypocalcaemia. Elevated levels of PTH can result in a Osteoporosis --> decreased bone integrity due to increased bone resorption You could develop Osteomalacia (rickets), a bone disease associated with low levels of 1,25D3

Answer 8

Treatment: Phosphate binders to bring phosphate levels down and reciprocally increase calcium levels Or Vit D analogues (to supress PTH production) Therefore because of secondary HPT you get => Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) - Amalgamation of bone diseases

Answer 9

FGF23 levels rise significantly due to the following renal diseases: Higher levels of FGF23, the more likely you are to have serious problems with your kidney disease.

Answer 10

Benign tumour secreting FGF23 - low serum levels of 1,25D3 This leads to osteomalacia

Answer 11

A Protein called PHEX usually degrades FGF23. A Mutations in the PHEX gene leads to elevated FGF23 and suppressed 1,25D3 which leads to ricket like bone diseases.

Answer 12

Rickets (in children) / osteomalacia (in adults) Caused by lack of calcium or vitamin D in the diet or due to lack of sunlight, Rarely inherited forms - mutation in vit D receptor, mutation of 1-alphahydroxylase, mutation in PHEX gene) Deficiency of Vitamin D (and or calcium) result in a failure to absorb sufficient calcium from intestines - leads to a lack of mineralisation of collagen component of bone (osteoid) This is called rickets when it affects growing skeleton and osteomalacia when affects adult skeleton.

Answer 13

Rickets: Osteoid at growth plate is weak which leads to bowing of legs Growth plate expands to compensate, to find more calcium to mineralise the bone --> swollen joints Osteomalacia: growth plate is already fused. But you get bone pain or pseudofractures (small fractures throughout bone) Treatment: vit D replacement (dietary or through sunlight)

Answer 14

The loss of bone mass and bone density --> decrease mineral & osteoid components of bone You have normal bone but there is less of it --> leads to increased fracture risk of wrist, spine and hip.

Answer 15

Osteoporosis of aging: male & females show gradual decline in bone density from early adult peak - women’s bone density is usually lower so the hip fracture threshold occurs earlier than in men Postmenopausal Osteoporosis: rapid decline in female bone density following decline in oestrogen at menopause (see below at age 50) Steroid-induced osteoporosis: decline in bone density and bone mass associated with the long-term use of steroids (glucocorticoids such as prednisolone) as a therapy for inflammatory diseases.

Answer 16

The higher your peak bone mass the less likely you are to reach fracture threshold. Because people are living longer people are more likely to reach fracture threshold when living.

Answer 17

As woman gets older you get gradual bending of spine (Kyphosis) because compression fractures in the vertebrae due to decrease in bone mineral density.

Answer 18

prevent fractures in individuals with low density Inhibition of osteoclast activity: Bisphosphonates (e.g. etidronate, risedronate, clodronate, alendronate), disrupt intracellular enzymes required for osteoclast activity. Stop osteoclasts from interacting and bone resorption form occurring. Most common treatment. Hormone replacement therapy: Oestrogen deficiency increases bone remodelling and bone resorption. Hormone replacement (oestrogen replacement) counteracts this. This is not recommended for all women as risk of CVD and cancer Inhibition of osteoclast development: Denosumab (RANK ligand antibody). Blocks RANK ligand on osteoblasts from interacting with RANK on osteoclasts, resulting in decreased differentiation of pre-osteoclasts. Stimulation of osteoblast activity (anabolic): intermittent use of PTH stimulates bone turnover without effects on osteoclasts. Allows rebuilding of bone to occur via osteoblasts. Teriparatide — first 34 amino acids of PTH is anabolic stimulator of bone formation

Answer 19

- Diagnosis of osteoporosis risk is made based on assessment of low Bone Mineral Density (BMD) using DEXA or ultrasound and laboratory investigations. - Optimal BMD may prevent osteoporotic fracture as you miss the fracture threshold. - Exercise, particularly during earlier life, promotes stress on bones. This stress is sensed by osteocytes which signals to other cells to enhance bone turnover early in life and maintain high BMD. - Vitamin D and calcium: helps maintain general bone health - Avoid smoking and high levels of alcohol intake