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Intro to Clinical Biochemistry > Bone homeostasis > Flashcards

Bone homeostasis Flashcards

1
Q

What is bone turnover influenced by?

A

Calcium, phosphate, magnesium metabolism
PTH and 1,25 (OH)2 D
Also other hormones such as TSH, cortisol, oestrogen and androgens

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2
Q

What is a key endocrinological axis invovled?

A

calcium-PTH axis

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3
Q

By what and how is calcium regulated

A

Via two hormones; PTH and 1,25 (OH)2 D (calcitrol)
Vitamin D - acts on kidney to reduce Ca excretion and the small intestine to increase absorption of calcium.

PTH senses serum calcium and can initate increased calcium similar to vit D or via calcium storages (bone) minerilisation
- PTH also acts to release phophate

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4
Q

What is the activation process of vitamin D?

A

Cholesterol in the skin becomes vitamin D3 upon light exposure. Vitamin D is firstly hydroxylated in the liver to 25 (OH) vit D. Then hydroxylated again in the kidney to produce active form - 1,25 (OH)2 D

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5
Q

How does PTH act on kidneys?

A

Induces 25-OH vit D-1-alpha hydroxylase to increase the activation of vit D

  • increases calcium reabsorption in the distal convoluted tubule
  • Decrease phosphate uptake in proximal tubule
  • Inhibits Na+H+ antitransporter activity which favors a mild hyperchloremic metabolic acidosis in hyperparathyroidism
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6
Q

PTH on the bone?

A

PTH stimulate bone resorption or bone formation depending on PTH conc and duration

  • chronic exposure leads to increased bone reabsorption.
  • PTH alters activity of osteoblasts and indirectly on osteoclasts
  • Occurs via the binding of PTH to receptor to generate cAMP second messenger for intracellular messaging
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7
Q

How is calcium homeostasis affected in renal failure?

A
  • Fall in Ca due to not enough activation of vit D
  • increase in phosphate, because kidneys dont excrete excess
  • increase in PTH - stimualted by low Ca. If continual then can cause secondary hyperparathyroidism
  • Renal failure leads to hypercalcaemiac due to hyperparathyroidism
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8
Q

True or false: Calcium is the only affector to PTH secretion.

A

False.
Changes in phosphate can indirectly affect PTH secretion.

Hypomagnasaemia has been shown to reduce PTH secretion as the process is Mg dependent.
- Not seen in mild hypomagnasaemia

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9
Q

Function of osteoblast

A
  • produce matrix which mineralises to form osteoid - coordinate minerlisation of bone
  • become quiescent and flatten to becom lining cells
  • respond to hormonal control to activate osteoclast
    • regulate osteoclast maturation by soluble factors and cognate interaction, resulting in bone resorption - also express the necessary RANKL
  • the osteoblast function requires high amounts of ATP
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10
Q

Function of osteocytes

A
  • cells inisde the bone which sense mechanical stres to initate remodelling
  • transport mineral into and out the bone
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11
Q

Function of osteoclasts

A
  • dissovle bone by solubiling mineral - resorption

- effects change in bone structure

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12
Q

Explain bone remodelling.

A

Osteoblasts produce RANKL which activates RANK on osteoclast precursors

  • stimulates cell to differentiate in mature osteoclast
  • activated RANK induces expression of c-Fos which binds to DNA and activates genes required for osteoclast function
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13
Q

Disorders of the bone?

A

Osteomalacia - inadequate minerilisation of bone
osteoporosis - reduced bone mineral density
Pagets disease - excessive reabsorption and formation leading to weak and misshapen bones
Renal osteodystrophy - kidneys fail to maintain Ca and PO4
Rheumatoid osteoarthritis - systemic inflammatory disease

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14
Q

Forms of calcium measurement.

A

Serum calcium and ionised calcium
- ionised is hard to measure, but can be done using a ABG machine

Adj Ca account for changes in albumin

  • albumin may mask hypercalcaemia
  • interpret with caution in extremes of pH
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15
Q

Forms of calcium measurement.

A

Serum calcium and ionised calcium
- ionised is hard to measure, but can be done using a ABG machine

Adj Ca account for changes in albumin

  • albumin may mask hypercalcaemia
  • interpret with caution in extremes of pH
  • guesstimate
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16
Q

Hypercalcaemia causes.

A

Increased Gi absorption - elevated Vit D or PTH
Increased bone resorption - increased bone turnover
Decreased bone minerilisation - elevated PTH
Decreased urinary excretion - elevated PTH and Vit D

Common causes:
primary hyperparathyroidism
Malignant disease

17
Q

Causes of hyperphosphataemia.

A

Pseudohyperphosphataemia - haemolysed specimen, myeloma, delayed seperation
Increased phosphate input - IV PO4, Rectal PO4, Cell death

Reduced phosphate excretion

  • Reduced eGFR due to acute or chronic renal failure
  • Increased renal tubule reabsorption can be physiological or pathological
18
Q

Causes of hypophosphataemia

A

Inadequate absorption

Abnormal urinary phosphate loss

  • primary or secondary hyperthyroidism
  • osmotic diuresis
  • Diuretic

Shifts of phopshate from ECF to cells

  • <1% in extracellular space
  • Recovery from DKA
  • Refeeding syndrome
  • Respiratory alkalosis
19
Q

Describe the two types of bone tissue.

A

Compact

  • Forms outer shell of bones consisting of very hard bones arranged in concentric layers
  • Account for 80% of bone mass

Cancellous

  • Located beneath the compact bone
  • Consist of a meshwork of bony trabeculae with many interconnecting spaces containing bone marrow
  • Accounts for remaining 20% of total bone mass but nearly 10x surface area of compact bone
20
Q

How is the differentiation/activation of osteoclasts regulated?

A
  • The activaiton of c-FOS activates IFN-beta which prevents further osteoclast activation
  • Furthermore, osteoprotegerin is soluble protein released from osteoblasts that bind to RANKL preventing RANK activation - competitive inhibition
21
Q

Match the following disorders

A. Osteomalacia
B. Rheumatoid osteoarthritis
C. Osteoporosis
D. Renal osteodystrophy
E. Pagets disease
  1. Systemic inflammatory disease
  2. Kidneys fail to maintain Ca and PO4
  3. Inadequate minerilisation of bone
  4. Excessive resorption and formation leading to weak and misshapen bones
  5. Reduced bone mineral density
A 
A3
B1
C5
D2
E4
22
Q

What occurs in calcium homeostasis during hypercalcaemia?

A
  • Increased Gi absorption
  • Increased bone resorption
  • Decrease bone mineralisation
  • Decreased urinary excretion
23
Q

What occurs in calcium homeostasis during hypocalcaemia?

A
  • Decrease GI absorption
  • Decreased bone resorption
  • Increase bone mineralisation
  • Increased urinary excretion
24
Q

Causes of hypocalcaemia?

A

Most common

  • Acute or chronic RF
  • Hypoparathyroidism
  • Hypomagnesaemia
  • Vit D deficiency

Parathyroid

  • agenesis
  • destruction

Non-thyroid

  • vit D deficiency or resistance
  • Altered Vit D metabolims
  • Acute pancreatitis
  • Acute rhabdomyolysis
25
Q

What are some technical errors that may cause low calcium readings?

A

EDTA contamination

Multiple transfusions with citrated blood products

26
Q

Hyperphosphatemia effect

A
  • Increase GI absorption
  • Increased bone resorption
  • Decrease bone mineralisation
  • Decrease urinary excretion
27
Q

What are some characteristics of hypophosphataemia

A
  • Decrease GI absorption
  • Decreased bone resorption
  • Increase bone mineralisation
  • Increased urinary excretion
28
Q

Causes of hyperphosphataemia

A

Pseudohyperphsophataemia occurs in haemolysed specimens

Reduced PO4 excretion

  • Reduced eGFR due to renal failure
  • Increased renal tubule reabsorption due to recovery from vit D deficiency or reduced PTH
29
Q

Causes of hypomagnesaemia

A 
Decreased intake 
Loss from body 
Renal
- Alcoholism
- Diuresis
- Drugs 
- Hypercalcaemia
30
Q

Causes of hypermagnesaemia

A
  • Impaired renal function
  • Large Mg load; IV contamination, post cardiac surgery

Rarely:

  • Excessive tissue breakdown
  • Lithium treatment
  • Addisons

Intro to Clinical Biochemistry (12 decks)

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