Calcium Metabolism Flashcards
What are the roles of calcium?
- Component part of the skeleton (99% of calcium here)
- Metabolic: action potential and intracellular signalling [NERVES AND MUSCLES]
What are the 3 forms of calcium and how much of the total calcium do they make up?
Free (ionised) - 50%
Protein Bound (albumin) - 40%
Complexed [bound] (citrate/ phosphate) - 10%
What is the normal total serum calcium?
2.2 - 2.5 mmol/L
What is the equation for corrected calcium?
serum Ca2+ + 0.02 * (40 – serum albumin in g/L)
ionised calcium can also be measured
If Albumin = 30 and total calcium = 2.2, what is the corrected calcium?
CC = 2.2 + (0.02 * (40 - 30)) CC = 2.2 + (0.02 *10) CC = 2.2 + 0.2 CC = xx mM
What does corrected calcium tell you?
Albumin is low, free calcium is normal
Why should we replace calcium in calcium and Vitamin D deficiency?
Calcium is important in nerve and muscle function so the body will take it from bone to maintain function
What is the body’s response to hypocalcaemia?
2 Part answer, 5 points
A. Parathyroid gland detects low Ca and releases PTH
B. PTH obtains Ca from
- Bone resorption
- Gut absorption (Via Vit D)
- Kidney resorption + renal alpha hydroxylase activation (Makes Vit D)
What are the two key hormones involved in calcium homeostasis and what are their roles?
- PTH- Works on Bone and kidneys, stimulates Vit D3 and renal phosphate wasting
- Vitamin D (Steroid hormone)- Works on Bone and Gut
How thicc is PTH?
84 Amino ‘Ass’ids
PHOSPHATE TRASHING HORMONE
How is Vit D made?
> 7 Dehydrocholesterol
Converted via UV
> Cholecalciferol D3
100% Converted via liver 25 hydroxylase
> 25-hydroxycholecalciferol (stored and measured form of Vitamin D)
Converted via kidney 1 alpha hydroxylase under PTH (rate limiting)
> 1,25-dihydrocholecalciferol
Which of Vit D3 and Vit D2 is made from plants?
Vit D2, also known as ergocalciferol
Which disease causes 1 alpha hydroxylase to be expressed in the lungs?
Sarcoidosis (lung disease)
What is the role of Vitamin D3? (5 points)
> Intestinal Ca absorption
> Intestinal Phosphate absorption
> Bone formation
Other:
> Vit D receptor controls many genes eg for cell proliferation, immune system etc
> Vit D deficiency associated with cancer, autoimmune disease, metabolic syndrome
What are the roles of the skeleton?
> Structural framework >> Strong >> Relatively lightweight >> Mobile >> Protects vital organs >> Capable of orderly growth and remodelling
> Metabolic - calcium homeostasis
> Calcium reservoir (+phsophate and magnesium)
What are the metabolic bone diseases?
> Osteoporosis
> Osteomalacia
> Paget’s disease
> Parathyroid bone disease
> Renal osteodystrophy
Summarise your knowledge of vitamin D deficiency based on it’s pathology, naming, epidemiology and risk factors.
Pathology: Defective bone mineralisation (crystals not on top of matrix)
Name: Childhood, rickets; Adulthood, osteomalacia
Epidemiology: >50% adults, 16% severe in winter
RFs: Lack of sun, dark skin, dietary, malabsorption
A Black patient with Crohn’s disease comes in after 15 months of minimal contact with the outside world with bone and muscle pain, you suspect osteomalacia, what investigation would you order?
Bloods- specifically calcium, phosphate and LFTs
X ray
A Black patient with Crohn’s disease comes in after 15 months of minimal contact with the outside world with bone and muscle pain, you suspect osteomalacia what would you expect on his blood results and x ray?
Bloods:
Low calcium and phosphate but raised ALP (due to increased osteoblastic compensation)
X ray:
Looser’s zones (cortical infractions, bone)
A Black patient with Crohn’s disease comes in after 15 months of minimal contact with the outside world with bone and muscle pain, what are your differentials?
- Osteomalacia/ Rickets
- Paget’s disease (bone pain)
- Myeloma/ malignancy
- non calcium - MSK like PMR, RhA
A young child enters with his mother who complains he has leg deformity, on inspection you notice bowing of the legs and swelling in the chest with widened epiphyses at the wrist. On power examination you notice power is not 5/5 and you suspect myopathy. What is this child likely to have?
Rickets disease
Swelling in chest = costochondral swelling
What might cause Osteomalacia?
Vitamin D deficiency (dietary history)
Renal failure (1 alpha hydroxylase- eGFR<15)
Anticonvulsants which break down Vit D (history/ blood titre)
Lack of sunlight (history)
Phytic acid (chappatis- history)
Why is osteoporosis bad?
Cause of pathological fracture
Occurring more often as people live longer
Loss of bone mass
Is bone structure normal in osteoporosis?
Bone slowly lost after age 20- Residual bone normal in structure
Which bone disease is normocalcaemic?
Osteoporosis
What disease should you think of when you see a neck of femur/ vertebral/ Colle’s fracture in an older patient?
Osteoporosis
What are the tests to investigate atypical fractures?
- Biochemistry
- DEXA
What does a T score signify?
Osteoporosis
-1 to -2.5 is osteopenia
T score is sd from mean of young healthy population
What are the causes of osteoporosis?
Age
Menopause (hormones) (early menopause: <45, early fracture risk)
Childhood illness (e.g. anorexia): Failure to attain peak bone mass so you arrive at fracture risk earlier
Lifestyle: sedentary, EtOH, smoking, low BMI/nutritional
Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings
Drugs: steroids
Others eg genetic, prolonged intercurrent illness
How do you treat osteoporosis?
Lifestyle:
> Weight-bearing exercise
> Stop smoking
> Reduce EtOH
Drugs:
> Vitamin D/Ca
> Bisphosphonates (eg alendronate) –↓ bone resorption - need to sit up while taking it and with plenty of water to avoid peptic ulcer
> Teriparatide injection (PTH derivative) – anabolic
> Strontium – anabolic + anti-resorptive
> (Oestrogens – HRT)
> SERMs eg raloxifene - licensed for osteoporosis
A patient comes in with confusion, a collateral history from the patients wife shows that the patient has been constipated for 4 days and is thirsty often, what blood tests would you order?
Bloods: U + E’s, LFTs, Haematinics
- If calcium high, repeat
- If persistently high, do PTH (and treat)
Acute (seizure/ coma): ABG
What is the biochemical boundary for hypercalcaemia?
> 3.0 mmol/ L
How does the PTH change in hypercalcaemia?
PTH decreases
A patient has high Calcium and you have determined they have suppressed PTH, what would you investigate for next?
- Malignancy
- Thyrotoxicosis
- Sarcoid, Vitamin D excess, milk alkali syndrome
A patient has high Calcium and you have determined they have an unsuppressed PTH, what would you investigate for next?
- Primary Hyperparathyroidism
2. Familial Hypocalciuric hypercalcaemia (rare)
What are the most common causes of Primary hyperparathyroidism?
Parathyroid adenoma/ hyperplasia/ carcinoma
MEN1
If a patient has high calcium in serum and urine, high PTH and low phosphate, which condition may the have?
Primary hyperparathyroidism
Which conditions does moans, groans and stones (and bones) come from?
Primary hyperparathyroidism- Hypercalcaemia (from high PTH)
What are the Calcium sensing receptors for?
PTH release regulation
Renal Ca resorption
FHH - has CaSR mutation, low urine Ca2+ and higher PTH release set point
What are the 3 types of calcium producing malignancy?
- Humoral hypercalcaemia of malignancy (eg small cell lung Ca, breast Ca)
> PTHrP - Bone metastases (eg breast Ca)
> Local bone osteolysis - Haematological malignancy (eg myeloma)
> cytokines
What can cause hypercalcaemia not based on the PTH feedback loop?
Malignancy
Sarcoidosis (non-renal 1α hydroxylation)
Thyrotoxicosis (thyroxine -> bone resorption)
Hypoadrenalism (renal Ca2+ transport)
Thiazide diuretics (renal Ca2+ transport)
Excess vitamin D (eg sunbeds…)
How do you treat hypercalcaemia?
Acute:
Fluids +++ 1L/ hour unless they have HF
Bisphosphonates if known cancer (BUT AVOID OTHERWISE)
Treat und`erlying cause
What is chvostek/ trousseaus a sign of?
Hypocalcaemia- neuromuscular excitability
How do you treat hypocalcaemia?
Calcium and vitamin D (calcichew)
Usually activated D3 unless it is a simple Vit D def
How do you go about management for hypocalcaemia?
- Repeat bloods and compare total with adjusted to look at albumin
- Investigate the PTH
What are the non PTH driven (PTH raised) causes of hypocalcaemia?
Vit D deficiency
CKD (can progress to tertiary hyperparathyroidism)
PTH resistance (pseudohypoparathyroidism)
What are the causes of hypocalcaemia with low PTH?
Surgical
Auto Immune hypoparathyroidism
Congenital absence of parathyroids (e.g. DiGEorge’s)
Magnesium deficiency (which is rqd in PTH regulation)
What is paget’s disease?
Focal disorder of bone remodelling
Which bones are most affected by Paget’s disease?
Pelvis
Femur
Skull
Tibia
A patient comes in with warm and painful areas of deformity, their bloods reveal no other abnormality except high ALP, what is the most likely cause?
Paget’s disease of the bone
How would you investigate a suspected Paget’s disease of the bone patient?
Nuclear medicine scan/ Xray
What is the treatment for Paget’s disease?
Bisphosphonates (for pain)
What can Primary hyperparathyroidism cause?
Osteitis fibrosa
What causes Renal osteodystrophy?
Due to secondary hyperparathyroidism + retention of aluminium from dialysis fluid
A patient complains of fractures but their bloods are all normal- which disease is most likely?
Osteoporosis
A patient complains of bone pain, his bloods reveal low-normal calcium and phosphate which is confirmed on re-test. The PTH has come back high as has the ALP. You finally remember to do Vit D which is low. Which condition is this characteristic of?
Osteomalacia (RIckets if child)
A patient comes in with Hot areas of bone pain, her bloods are normal apart from a raised ALP, what is this most likely from?
Paget’s disease of the bone
A patient comes in with confusion and seizures, an ABG shows hypercalcaemia, after treating with fluids you do a blood test which reveals high PTH, low phosphate, normal Vit D and high normal ALP. Which condition is this typical of?
Parathyroid bone disease (Primary hyperparathyroidism)
A patient arrives at the renal clinic feeling unusually tired with tingling in his finger tips. His bloods show normal glucose but his U&E’s show low calcium and high phosphate. You want to confirm this result and also add PTH, Vitamin D and ALP onto the next bloods- what are you likely to see?
PTH is low
Vitamin D is normal
ALP is high-normal
What do osteoblasts release?
ALP- can be measured
What do osteoclasts do?
Resorption of bone
What is PTHrp?
Placental hormone that allows skeleton in foetus
Might see it in cancer patients
What are the symptoms of primary hyperparathyroidism?
Bones
Moans (psychic)
Stones
Groans (abdominal)
What does lithium cause?
hypercalcaemia
What ECG changes occur in hypocalcaemia?
Prolonged QT
