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Year 2 LCRS > Musculoskeletal 2 - MBD Biochemistry > Flashcards

Musculoskeletal 2 - MBD Biochemistry Flashcards

1
Q

What makes bone strong?

A
  • Mass
  • Material properties (collagen, woven vs lamellar, mineralisation, microcracks)
  • Microarchitecture (trabecular thickness, connectivity, and cortical porosity)
  • Macroarchitecture (hip axis length, diameter)
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2
Q

List the biochemical investigations in bone disease

A

Serum:

  • Bone profile (calcium, corrected calcium, phosphate, alkaline phosphatase, creatinine)
  • Renal function (PTH, 25-hydroxy vitamin D)

Urine

  • Calcium/phosphate
  • NTX (N Telopeptide of Collagen)
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3
Q

List the biochemical changes in osteoporosis

A
  • No change in chalcium, phosphate, or alkaline phosphatase
  • Increase or no change in bone formation
  • Increase in bone resorption
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4
Q

List the biochemical changes in osteomalactia

A
  • Calcium may be the same or decreased
  • Low phosphate
  • High alkaline phosphatase
  • Low vitamin D
  • High PTH
  • High urine phosphate
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5
Q

List the biochemical changes in pagets

A
  • Calcium the same or increased
  • Phosphate the same
  • Alkaline phosphatase increased
  • Hone formation increased
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6
Q

List the biochemical changes in primary hyperparathyroidism

A
  • High calcium
  • Low or normal phosphate
  • Low or normal alkaline phosphatase
  • Increased bone resorption
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7
Q

List the biochemical changes in renal osteodystrophy

A
  • Decreased or normal calcium
  • Increased phosphate
  • Increased alkaline phosphatase
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8
Q

List the biochemical changes in metastases

A
  • Increased calcium
  • Increased phosphate
  • Increased alkaline phosphatase
  • Increased bone resorption
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9
Q

How are serum calcium measurements corrected?

A
  • Conc calcium + 0.02(45 - conc albumin)
  • High albumin will result in lower true (free) calcium
  • 47% free ionised
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10
Q

Describe parathyroid gland production of PTH

A
  • Inverse sigmoidal function between PTH and calcium levels
  • Even at high calcium levels there is a base-line PTH secretion (MINIMUM)
  • The set point is the point if half maximal suppression of PTH (steep part of slope). A small alteration causes large change in PTH
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11
Q

Describe calcium reabsorption and resorption caused by PTH

A
  • Active calcium absorption in the distal tubule of kidney
  • Sodium calcium exchanger and calcium ATPase
  • Reabsorption via calbindin
  • Bone resorption through the RANK system (increases RANK-L which causes activation of osteoclasts)
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12
Q

List the stats relating to primary HPT and its causes

A
  • 50s female 3:1 male (2% post menopausal develop)

Causes

  • Parathyroid adenoma (80%)
  • Parathyroid hyperplasia (20%)
  • Parathyroid CA (<1%)
  • Familial syndromes (MEN1, MEN2A, HPT-JT)
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13
Q

How is primary HPT diagnosed?

A
  • Elevated total/ionised calcium with PTH levels frankly elevated (or high normal)
  • Decreased serum phosphate
  • Hypercalcaemia and high PTH subjects in the normal range are not normal physiologically due to lack of inhibition
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14
Q

Why do patients with primary hyperparathyroidism get polydipsia and polyurea?

A
  • High serum calcium causes diuresis
  • Calcium is absorbed passively transceulluarly
  • Increased water enters collecting duct (calcium of 3 is the same as taking frusemide)
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15
Q

How does activated vitamin D affect gut calcium absorption?

A
  • Increases
  • Passive paracellular linear
  • Active in the duodenum
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16
Q

List the classical vitamin D actions

A
  • Reabsorption of calcium and phosphate in the duodenum (MAIN)
  • Increases osteoblast formation and synergises with PTH
  • Facilitates PTH in the kidney to increase calcium reabsorption
  • Reduces PTH secretion and increases FGF-23 production from bone
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17
Q

What is the definition of vitamin D deficiency?

A
  • 75nmol/L as muscle function is better at those levels.

- PTH levels rise below this.

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18
Q

List the symptoms and signs of rickets

A

Symptoms

  • Bone pain and tenderness (axial)
  • Muscle weakness (proximal)
  • Lack of play

Signs

  • Age dependent deformity
  • Myopathy
  • Hypotonia
  • Short stature
  • Tenderness on percussion
19
Q

List the vitamin D related causes of rickets/osteomalacia

A
  • Dietary
  • GI - malabsorption, pancreatic insufficiency, liver/biliary disturbance, drugs (phenytoin/phenobarbitone)
  • Renal (chronic renal failure)
  • Rare hereditary (vitamin D dependent rickerts type 1 deficiency of 1 a hydroxylase or type 2 defective VDR for calcitriol)
20
Q

How does FGF-23 act?

A
  • Produced by osteoblast lineage cells when high phosphate is detected at the bone (following absorption in the gut)
  • Causes phosphate loss
  • Inhibits activation of vitamin D by 1 alpha hydroxylase
21
Q

What does FGF-23 excess cause?

A

Rickets/osteomalacia

22
Q

List the genetic and acquired causes of osteomalacia due to hypophosphataemia?

A
  • Kidney looses phosphate
  • Hypophasphataemia can be isolated - eg. X-linked hypophosphataemic rickets (FGF-23 levels permanently high) or autosomal dominant hypophosphataemic rickets
  • Oncogenic osteomalacia (mesenchymal tumour produces FGF-23)
  • Fanconi syndrome
23
Q

What is fanconi syndrome?

A

Damage of the kidney proximal tumour causes phosphaturia and stops 1a hydroxylation of vitamin D

24
Q

List causes of osteoporosis

A

High turnover (increased resporption greater than increased formation)

  • Oestrogen deficiency
  • Hyperparathyroidism
  • Hyperthyroidism
  • Hypogonadism
  • Heparin
  • Cyclosporine

Low turnover (decreased formation more pronounced than decreased resorption)

  • Liver disease
  • Heparin
  • Age over 50

Increased resorption and decreased formation
- Glucocorticoids

25
Q

How does oestrogen deficiency cause menopausal bone loss?

A
  • Oestrogen inhibits PTH release
  • Increased number of remodelling units
  • Remodelling imbalance with increased bone resorption (90%) compared to bone formation (45%)
  • Remodelling errors - deeper and more resorption pits(trabecular perforation and cortical excess excavation)
  • Decreased osteocyte sensing
26
Q

How is osteoporosis diagnosed?

A
  • Biochemistry is used to exclude other causes
  • Biochemistry will be normal if primary
  • Check for vitamin D deficiency, hyperparathyroidism, hyperthyroidism and hypogonadism
  • Exclude multiple myeloma
  • High urine calcium
  • DEXA scans (single best predictor of fracture risk)
27
Q

How do DEXA scans work?

A
  • Measure transmission through the body of X rays of two different photon energies
  • Dual energy X ray absorptiometry
  • T-score is compared to a 25 year old bone density
  • Measure at vertebral and hips (commonest types of fracture, vertebral responds quickly to treatment)
28
Q

List the markers of bone formation?

A
  • Alpha 1 and Alpha 2 chains of type 1 collagen produced by osteoblast form extension peptides
  • Extension peptides can be measured in the blood (eg. P1NP formed from procollagen)
29
Q

List the markers of bone resorption?

A
  • Serum CTX (carboxy-terminal collagen crosslinks)
  • Urine NTX (N-telopeptide of collagen - stable product of bone resorption)
  • Used in monitoring the response to treatment
  • From collagen breakdown
30
Q

List the problems with urinary collagen cross links

A
  • Reproducibility
  • Positive association with age
  • Need to correct for creatinine
  • Diurnal variation in urine markers (higher in the morning, as bone grows most at night)
31
Q

What is alkaline phosphatase used to diagnose and monitor?

A
  • Pagets
  • Osteomalacia
  • Boney metastases
32
Q

What is BSAP?

A
  • Bone specific alkaline phosphatase
  • Tissue specific form (liver vs bone) so can be used to see if it is from bone or the liver
  • Essential for mineralisation, regulating concentration of phosphocompounds
  • Increased in pagets, osteomalacia and bone metastases
33
Q

List the possible pathways of metabolic bone disease

A
  • Increasing bone resorption
  • Decreasing bone formation
  • Altering bone structure
34
Q

How active is cancellous bone?

A
  • Remodelling 5% anytime
  • Total skeleton remodells over 7 years
  • Continuous exchange of ECF with bone fluid reserve
35
Q

How is peak bone mass affected by exercise?

A
  • Increases bone dimensions and changes bone shape
  • Changes trabecular volumetric BMD
  • Bone modelling by bone growth in the periosteum and resorption of endosteum to push the bone outwards (happens in males more, females grow less and have more endosteum)
36
Q

Describe the bone remodelling process

A
  • Crack is formed, and setected by the osteocytes.
  • Osteocytes apoptose to release RANKL. They signal for haematopoietic cells to enter the bone, differentiate to the osteoclasts and perform resorption of bone
  • Osteoblasts then reverse this by remanufacturing and laying down new bone, which is then mineralised.
  • Osteoblasts form new lining cells or new osteocytes
  • Osteoclasts last a few weeks, and osteoblasts months
37
Q

List the effects of PTH

A
  • Increase bone resorption to releae calcium and phosphate
  • Increase phosphate excretion
  • Increase calcium reabsorption
  • Increase calcitriol formation
  • Increase CaHPO4 absorption
38
Q

List the clinically relevant points relating to PTH

A
  • Mg dependent
  • Half life 8 minutes
  • The receptor is also activated by PTHrP (tumours)
39
Q

What percentage of patients with elevated PTH get kidney stones?

A

20%

40
Q

When is operation performed in primary HPT?

A
  • Calcium 0.25mmol/l
  • > 10mmol 24 hour urine calcium or stones
  • Reduced Creatinine clearance (<60)
41
Q

List the consequences of hypocalcaemia

A
  • Neuromuscular irritability (parasthaesias, muscle twitching, seizures, bronchospasm)
  • Cardiac signs (hypotension, heart failure, arrythymia, prolonged QT interval)
  • Trousseaus sign and chvosteks sign
42
Q

List the causes of fanconi syndrome

A
  • Multiple myeloma
  • Heavy metal poisoning (lead/mercury)
  • Tenofovir or gentamycin
  • Congenital disease (wilsons, glycogen storage diseases)

MOST COMMON CAUSE of hypophosphaemia

43
Q

What is used to measure response to anabolic treatments?

A

P1NP (procollagen type 1 N propeptide) rises to peak in 3 months and predicts response

44
Q

What is renal osteodystrophy?

A
  • Increasing serum phosphate
  • Reduction in 1,25 vitamin D
  • Secondary hyperparathyroidism develops (GFR under 60)
  • Unsuccessful and hypocalcaemia develops
  • Later the parathyroids become autonomous causing hypercalcaemia

Year 2 LCRS (128 decks)

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