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Medicine - Year 1 > Bone Pain - Biochemistry > Flashcards

Bone Pain - Biochemistry Flashcards

1
Q

Describe the hydroxylation of vitamin D

A
  1. Supply is from the sun (Pro-vitamin D3), limited numer of foods (Vitamin D3) and food supplement (Vitamin D2) which is known as calciferol
  2. Calciferol is hydroxylated in the liver to form calcidion (25 hydroxy vitamin D = 25OHD)
  3. Calcidiol is converted into the active hormone, calcitriol [1,25 Di-hyrdoxy vitamin D = 1,25(OH)2D]
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2
Q

Calcium and phosphate are regulated through 4 important organ systems. Descibe the role of each organ.

A
  1. The gut - where calcium and phosphate are absorbed
  2. Bone- where calcium and phosphate are mineralised and resorbed
  3. Kidneys - where the quantity of calcium of phosphate is regulated, and they are absorbed from pre-urine
  4. Thyroid gland - calcitonin (CT), parathyroid hormone (PTH)
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3
Q

Describe the function of calcium in plasma and bone

A

Plasma Ca

  • 50% protein bound (Abumin
  • 50% ionised

Bone

  • Stiffness and structure
  • -1kg calcium in average body size
  • Stored in hydroxapatite - 99% (combination f calcium, phsophate and hydroxy)
  • ‘Resevoir’ for plasma Ca - If too little Ca is coming in from the gut/too much Ca is lost from urine it is replenshed
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4
Q

List 5 regulatory functions of calcium

A
  1. Neurotransmission
  2. Reproduction
  3. Hormone action
  4. Cellular growth
  5. Enzyme growth
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5
Q

What is the normal range of plasma (albumin adjusted) calcium?

A

Albumin adjusted calcium is between 2.2 and 2.6 mmol/L

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6
Q

a) What level of Ca is considered as hypocalcaemia?
b) List the signs and symptoms of hypocalcaemia

A

a) Albumin adjusted Ca

b)

  • Parathesia (numbness, tingling)
  • Muscle spasm and tetany (a disorder of increased excitability)
  • Chvostek’s sign (twitching of facial msucles in response to tapping over the facial nerve) and Trousseau’s sign (carpopedal spasm induced by pressure applied to the arm by an inflated sphygmomanometer cuff)
  • Seizures/fits
  • Cardic abnormalities including arrythimias, hypertrophy, hypotension, cardiac failure
  • Coma
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7
Q

a) What level of Ca is considered as hypercalcaemia?
b) List the signs and symptoms of hypercalcaemia

A

a) Albumin adjusted Ca > 2.6 mmol/L

b)

  • Nausea
  • Peptic ulcers
  • Renal stones
  • Renal failure
  • Polyuria
  • Soft tissue calcification
  • Mental disturbances
  • Depression
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8
Q

Describe the difference between the main role of parathyroid horomone (PTH) and calcitonin (CT)

A

Parathyroid hormone acts to increase blood calcium levels, while calcitonin acts to decrease blood calcium levels.

Therefore CT opposed the role of PTH

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9
Q

a) What is the main role of parathyroid hormone (PTH)
b) Describe 5 speicifc roles of Parathyroid hormone (PTH)

A

a) Parathyroid hormone acts to increase blood calcium levels

b)

  1. Stimulates bone resorption, particularly when plasma Ca is high, by stimulcating osteoblastic function
  2. Stimulates release of calcium into plasma when plasma Ca is low
  3. Stimulates absorption of Ca in the kidneys to decrease urinary loss of calcium
  4. Increases urinary excretion of phosphates to decrease plasma phosphate
  5. Stimulates the production of active hormone vitamin D (1,25 Vit D) which in turn stimulates the absorption of calcium and phosphate from food in the intesine
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10
Q

a) What is the main role of calcitonin (CT)
b) Describe the role of Calcitonin (CT)

A

a) CT acts to decrease blood calcium levels
b) CT increases when Ca plasma increases.It inhbitis the activity of osteoclasts to prevent bone resorption. This prevents Ca and phosphate from being released into the blood. This ensures that Ca that is in bone remains there and urinary calcium excretion is increases

CT opposes the role of parathyroid hromone

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11
Q

What is the main and most important role of 1,25 hydroxy vit D [1,25(OH)2D]

A

To increase calcium and phosphate absorption from food in the gut

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12
Q

Describe the 4 roles of 1,25 hydroxy vit D [1,25(OH)2D] in bone

A
  1. Stimulates bone resorption, particularly when PTH is also high
  2. Stimulates calcium incorporation in growth plates and bone
  3. Chondrocyte and osteoblast maturation
  4. Bone formation and mineralisation
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13
Q

Describe the 2 roles of 1,25 hydroxy vitamin D in the parathyroid gland

A
  1. Inhibits Ca and phosphate
  2. Indirectly and directly decreases the amount of PTH that is releases from the parathyroid gland
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14
Q

Discuss the role of vitamin D [1,25(OH) Vit D] in bone metabolism

A
  1. Main and most important action is to increase calcium and phosphate absorption from the food in the gut
  2. Function in bone
  • Stimulates resorption, partculary when PTH is also high
  • Stimulates calcium incorporation in growth plates and bone
  • Chondrocyte and osteoblast maturation
  • Bone formation and mineralisation
  1. Stimulates (in congestion with PTH) calcium reabsorption (not a strong effect)
  2. Inhibits its own production of 25 Vit D (precursor) and stimulates its own breakdown metabolism
  3. Parathyroid gland
  • Inhibits Ca and phosphate
  • Indirectly and directly decreases the amount of PTH that is released from the parathyroid gland
  1. Stimulates FGF23
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15
Q

Describe the 2 roles of fibroblast growth factor (FGF23)

A
  1. Stimulates the excretion of phosphate in urine
  2. Has a major effect on vitamin D metabolism - particulary stimulates catabolism of 1.25 Vit D and 25 Vit D to non-active metabolites
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16
Q

Intestinal Ca absoroption varies between 15-50%. List 4 things that percentage Ca absorption depends on

A
  1. Intake
  2. Active absorptions
  3. Life stage (postmenopausal decreases 0.21%)
  4. Physiological state: growth, pregnancy, lactation
17
Q

List 3 sources of calcium

A
  1. Dairy products
  2. Cereals and cereal products
  3. Green leafy vegetables
18
Q

List 3 sources of Vitamin D

A
  1. Majority: Skin synthesis
  2. Diet: oily fish, meat, eggs, fortified spreads
  3. Fortified cereals and cereal products
19
Q

List 4 causes of calcium deficiency

A
  1. Low supply - low dietary intake of dairy
  2. Low absorption - Vit D deficiency
  3. Low absorption - phosphate and phytate binding
  4. GI disorders leading to low absorption
20
Q

List 5 causes of vitamin D deficiency

A
  1. Low sunshine exposure
  2. Low dietary supply - low consumption of Vit D rich foods, nenonatal anc infancy
  3. Low absorption
  4. Obesity
  5. High loss and/or utilisation
21
Q

What can both calcium and vitamin D deficiency lead to?

A

2’hyperparathyroidism

22
Q

Describe calcium resorption in kidney

A
  • In a healthy kidney the huge amount of Ca sent there is 97% reabsorbed and that takes place throughout the whole of the kidney
  • In distal convulated tube is only where PTH mediated Ca reabsorption takes place. Iplies PTH only has a limited capacity to ensure not much Ca is lost
23
Q

Describe phosphate reabsorption and excretion in kidneys

A
  • In a healthy kidney reabsorption of phosphate % is dependant on dietary intake
  • The kidneys plays a key role in excreting phosphates if too much is consumed
  • In renal impairment the body has an issue excreting phosphates, causing hyperphosphatemia. This is associated with a strong risk of increase in CVD
24
Q

Describe the function of the endocrine system in vitamin D metabolism

A
  1. Vit D from diet is hydroxylated in the liver
  2. This circulates in the liver
  3. Then goes to the kidneys where it’s converted to 1,25(OH)2Vit D
  4. This is returned again
25
Q

Describe the relationship between 25OHD and 1,25OHD

A
  • Plasma [250OH Vit D] and [1,25(OH)2Vit D] are not or only weakly related
  • Plasma [1,25(OH)2Vit D] is weakly related to functional or health outcomes and vary tightly regulated
26
Q

Describe the auto/paracrine function in vitamin D metabolism

A
  • A lot of 25OH is not hyrdoxylated in the kidney for endocrine effects and therefore reflected in plasma
  • However, alot of 25OH is also hyrodxylated in all kinds off tissue e.g., breast tissue, placenta, bone and intestines
  • A lot of 1,25OH is broken down in these tissues and therefore no reflected in plasma
  • This is why if you want to know about vitamin D status and its availability to the body you measure 25OHD and not 1,25OHD because it doesn’t reflect its function in plasma
27
Q

If you want to know about vitamin D status and its availability to the body, why must you measure 25OHD and not 1,25OHD?

A
  • Alot of 25OHD is also hydroxylated in all kinds of tissue e.g., breast tissue, placenta, bone, and intestines
  • A lot of 1,25OHD is broken down in these tissues so it is not reflected in plasma
  • This is why if you want to know about vitamin D status and its availability to the body you measure 25OHD and not 1,25OHD because it doesn’t reflect its function in plasma
28
Q

List the clinical symptoms of vitamin D deficieny in adults and children

A
  • Non-specific
  • Fatigue
  • Generalized muscle, joint and bone pain, and hyperalgesia (increased severity to pain)
  • Muscle weakness, especially of the extremities and pelvic region manifesting in difficulties in rising from a sitting or squatting position or a wadling gait
  • Fragility fracture, with prolonged bone loss
29
Q

List the clinical symptoms of vitamin D deficiency specifically in children

A
  • Bone deformities
  • Cardiac problems
  • Hypocalcaemic fits
30
Q

List the groups of people who are at increases risk of low 250HD (of a general healthy population) and explain why this is the case

A
  • Dark skinned individuals - can produce same amount of Vit D in skin but takes loneger because the pigment in their skin acts as a barrier for UVB
  • Concealing dress style - little UVB exposure
  • Little UVB exposure
  • Obesity - bigger distribution volume
  • Adolescents - may be due to diet and use of Vit D for growth spurt
  • Frail eldery - limited exposure to sun + lose a lot of Vit D through kidney
  • Exclusively breast-fed babies - very little vid D in breast milk (so Vit D needs to be supplemented in from birth onward)
  • Winter
  • Specific groups including: renal disease, GI disorders, coeliac, ICU patient, sever liver disease, tuberculosis, HIV
31
Q

Name 2 conditions caused by vitamin D deficiency

A
  1. Rickets
  2. Osteomalacia
32
Q

What processes are affected in Rickets?

A
  • Chondrocyte function affected (hypertrophy) and leading to apoptosis of chondrocytes
  • Lack of calcification of GP cartilage
33
Q

What processes are affected in osteomalacia

A
  • Lack of calcification of osteoid
  • Osteoblast, osteoclast and osteocyte function affected
34
Q

Describe what is needed to diagnose rickets

A
  • Clinical features - widening of growth plates (most detectable in wrists, knees, and ribs)
  • Radiology - widening of growth plates, bowing of legs
  • Medical and diet history
  • Biochemistry - Blood (25OHD, Ca adjusted for albumin, bone alkaline phosphatase) and urine (Calcium and phosphate)
35
Q

Describe the role of vitamin D supplements in older people

A

Bone

  • Prevention/treatment of bone loss and osteoporosis
  • Prevention/treatment of 2’hyperparathyroidism
  • Prevention/treatment of osteomalacia
  • Treatment of bone pain

Physcial perfromance and fall risk

  • Skeletal muscle mass and strength postively related to bone density
  • Fall prevention and improvement of balance
  • Treatmentof muscle pain and weakness

Important as co-therapy when on osteoporosis treatment

Medicine - Year 1 (61 decks)

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