PBL 12- Osteoporosis Flashcards

Question

Calcitriol: How is it synthesized? What are its actions? Solubility/binding?

Answer 1

· Vitamin D3 must be metabolised within the body to become the active form - calcitriol • Liver forms the intermediate form - Calcidiol • Kidney transforms this into the active form calcitriol under the stimulation of PTH · The lipid soluble hormone Binds to intracellular Vitamin D receptors · Effects gene expression to cause protein synthesis ``` Acts on · Bone: • Regulates bone remodeling · Gut • Inreases calcium and phosphate absorption · Muscle • Increases growth , strength and contraction · Increases immune function · Decreases inflammation · Epithelial cells • Increases differentiation • Decreases proliferation • Causes apoptosis ```

Answer 2

· It is not efficiently absorbed | · Calcitriol controls synthesis of genes and increases expression of proteins that promote transcellular transport of ca

Answer 3

PTH · Low calcium causes stimulation of PTH secretion · PTH acts directly on bone to induce osteoclastic resorption from bone · PTH increases synthesis of Calcitriol by the kidney · PTH increases reabsorption of calcium from the glomerular filtrate preventing loss in the urine Calcitriol · Calcitriol increases intestinal absorption of calcium · Calcitriol can stimulate osteoclasts indirectly by stimulating osteoblasts to release factors that stimulate differentiation • Not as potent as PTH • Slow acting • Role in normal bone remodeling

Answer 4

PTH · Inhibition of PTH synthesis · Decrease in PTH levels · Less mobilization of calcium from the bones Calcitriol · Enhances absorption of Ca and phosphorus from the small intestine · This helps to maintain a proper balance that assists Calcitonin to mineralize the bone matrix Calcitonin · Reduces osteoclastic bone resorption and allows excess calcium to deposit in bones · Decreases PTH synthesis

Answer 5

· More than 40% of the world is vitamin D deficient · 1 in 5 children ``` · Can be due to : • Reduced intake • Age related factors • Decreased sun exposure • Sunscreen use • Decline in renal function ``` · Mild to moderate deficiency • Decreased calcium absorption resulting in decreased serum calcium • Increased PTH causing increased tubular resorption of calcium and bone resorption • Decreased bone density • High bone turnover • Increased fracture risk in older people · Severe Vitamin D deficiency • <15 nM • Blood calcium below normal • Can cause secondary hyperparathyroidism ○ PTH also causes phosphorus loss via the urine leading to a decreased serum phosphate ○ This imbalance causes a defect in bone mineralization • Children get rickets • Adults get Osteomalacia

Answer 6

· It is the most abundant mineral after calcium · The bulk is stored in bone (85%) as mineralized hydroxyapatite ECM giving the bone strength · Every cell contains phosphate anions • Complexed to proteins or lipids • Nucleic acids in DNA and RNA • Needed for energy production • Used as a chemical buffer in serum and urine · Most unprocessed food has it

Answer 7

Renal cotransporter: • There are sodium- phosphate co transporters in the proximal renal tubular cells • If there is low dietary phosphate intake there is an increase in expression of transporters leading to increased renal phosphate absorption • In excess intake the opposite occurs and there is less transporters expression and more phosphate is excreted in urine FGF-23 · FGF 23 = 23 fibroblast growth factor (phosphaturic hormone) · Secreted from bone · Works on the kidney · Secreted in response to HIGH dietary intake or serum phosphate levels · It works on the Sodium phosphate cotransporter to decrease expression of transporters · Causes: • Inhibition of phosphate reabsorption (Similar to PTH) • Increased excretion of phosphate (Similar to PTH) • Decreases calcitriol synthesis resulting in decreased gut phosphate absorption (Opposite to PTH) · Aim: • To decrease serum phosphate level

Answer 8

· Phosphate levels will become too decreased · Linked to rare forms of hereditary hypophosphataemic rickets and osteomalacia · Most often found in chronic kidney disease • Decreased glomerular filtration • Decreased kidney phosphate excretion • Increased FGF 23 secretion from bone • Decreased calcitriol through inhibition of hydroxylase in the kidney • Low blood calcium • Secondary hyperparathyroidism

Answer 9

PTH : · Increases Calcium · Decreases Phosphate Calcitriol · Increases Calcium · Increases Phosphate

Answer 10

``` · > 2.6 · Hyperparathyroidism • Primary, secondary, tertiary · Increased absorption of calcium · Malignancy · Vitamin D intoxication · Thiazide diuretics · Renal insufficiency · Thyrotoxicosis · Familial hypocalciuric hypercalcaemia · Sarcoidosis ```

Answer 11

``` · Neurological: • Confusion • Lethargy • Headaches • Depression • Coma · Abdominal: • Nausea and vomiting • Abdominal pain • Polyuria, polydipsia • Pancreatitis • Kidney stones · Other: • Dehydration • Bradycardia • Renal failure • Muscle fatigue ```

Answer 12

``` · < 2.25 · Osteomalacia : vitamin D deficiency · Chronic renal failure · Hypoparathyroidism · Alkalosis · Hypomagnesaemia · Acute pancreatitis · Alcoholism · Chronic diarrhoea · Hyperventilation · Malabsorption ```

Answer 13

``` · Cardiovascular: • Long QT intervals • Hypotension • Heart failure · Neuromuscular • Cramps / spasms • Tetany • Bronchospasms · Neurological: • Irritability • Seizures /Convulsions • Hyperreflexia • Positive chvostek sign • Positive trousseau sign • Parathesias · Abdominal • Intestinal cramps • laryngospasm ```

Answer 14

· Increase absorption of phosphate ○ Excess use of some laxatives and enemas ○ Excess Vit D · Shift of phosphates from cells into blood ○ High levels of cell destruction –metastatic tumour cell lysis during chemotherapy · Inadequate excretion of phosphate ○ Renal failure ○ Hypoparathyroidism

Answer 15

``` · Neuromuscular: • Muscle cramping / Muscle twitching • Tetany • Hyperreflexia • Hypotension · Neurological: • Confusion • Paraesthesia • Seizures • Coma · Other: • Soft tissue calcification – Aching, stiff joints • Alkalosis • Itching skin • Cardiac dysrhythmias ```

Answer 16

``` · Inadequate absorption of phosphate • Chronic diarrhoea • Vomiting • Malabsorption • Misuse of phosphate-binding antacids • Chronic alcoholism • Vit D deficiency · Shift of phosphate from blood into cells • Respiratory Alkalosis • Insulin administration • Adrenalin administration · Excessive phosphate excretion • Increased diuresis • Hyperparathyroidism · Other: • Severe burns • Severe sepsis ```

Answer 17

``` Role: · Nerve and muscle function · Neurotransmission · Bone structure · Constituent of several enzymes ``` Stored: · 50% is stored in the bone and muscle · 1/3 is bound to protieins ``` Dietary source: · Green vegetables · Cereal · Nuts · Dairy products ```

Answer 18

``` · Increased absorption of Mg: • Excessive use of Mg-containing antacids • Excessive infusion of Mg · Decreased excretion of Mg: • Renal failure • Metabolic acidosis ```

Answer 19

``` · Neuromuscular: • Decrease in deep tendon reflexes - Hyporeflexia • Muscular weakness • Paraesthesia • Paralytic ileus · Other: • Platelet aggregation • Hypotension • Dysrhythmia • Respiratory depression • Drowsiness and lethargy • Flushed skin and sweating • Cardiac arrest ```