ChemPath - Calcium handling and metabolism Flashcards by Alexandra Chan

What are the forms of calcium in the body

bone - 99%

Blood/serum - 1%
Free/ionised (50%) - biologically active (important for nerves)
Protein-bound (40%) - bound to albumin
Complexe (10%) - citrate/phosphate

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What us calcium needed for

Nerve function
Muscle function
Bone formation and maintenance

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What is corrected calcium and how is it calculated

corrected calcium = serum Ca + 0.02(40-serum albumin)

When albumin conc. falls, the calcium is released and so the free calcium level remains the same despite an appearance of low calcium. If albumin is abnormal, this means that the Ca appears abnormal, but the corrected calcium would be NORMAL.

If corrected calcium is still abnormal - problem is not albumin

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What is the role of PTH

84aa protein released from the thyroid

Bone resorption for Ca release (osteoclast stimulation)
Renal resorption of Ca + phosphate excretion
Renal 1 a-hydroxylase activation (vit D synthesis)
Intestinal Ca absorption

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Describe the vitamin D’s role in calcium homeostasis

7-dehydrocholesterol in the skin is converted to cholecalciferol/vitamin D3 on exposure to UVB light
Vitamin D from UVB (D3) or the diet (D2) is converted to 25-OH-D3 in the liver via 25 hydroxylase
Renal 1 𝛼-hydroxylase is stimulated by PTH
Renal 1 𝛼-hydroxylase converts 25-OH-D3 to calcitriol/1,25(OH)2D3
Increased Ca reabsorption in the kidney and gut. Increased bone calcium maintenance
-ve feedback on PTH

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What is the difference between ergocalciferol and cholecalciferol

ergo = vit D2, chole = vit D3
Vit D2 - plant product (therefore vegan), Sourced from the diet
vit D3 - synthesised in the skin

Both are active, there is the difference of a double bond between them

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What is the role of calcitriol (1,25 dihydroxy-vitamin D)

Active form of vit D
1. Intestinal Ca AND phosphate absorption
2. Renal Ca absorption
3. Bone Ca maintenance

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Why might people with sarcoidosis get hypercalcaemia

1-alpha hydroxylase can be expressed unregulated in lung cells of sarcoid tissue → increases renal and intestinal abs. of Ca

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Give examples of metabolic bone disease

Osteoporosis (bone normal but weak)
Osteomalacia (vit D deficiency)
Paget’s disease
Parathyroid bone disease
Renal osteodyrstophy

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Describe vit D deficiency (what it causes), adults v children, % prevalence)

Defective bone mineralisation

Children - ricketts
Adults - osteomalacia

> 50% of adults have insufficient vit D, and 16% have severe deficiency in Winter and Spring

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What are the risk factors for vit D deficiency

Lack of sunlight exposure
Dark skin
Dietary
Malabsorption
Pregnancy
breastfeeding from a mother with vit D deficiency

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What are the causes of osteomalacia

Vitamin D deficiency
Renal failure
Anticonvulsants e.g. phenytoin (induces breakdown of active vit D)
Lack of sunlight
Phytic acid (found in Chappati flour)

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What are the clinical features of osteomalacia and ricketts

Ricketts
* Bowed legs
* Costochondral swelling (lumps on the chest)
* Widened epiphyses at the wrists
* Myopathy (waddling gait)
Low calcium and phosphate

Osteomalacia
* Bone & muscle pain
* Increased fracture risk
* Looser’s zones (Pseudofractures that will not break until under pressure/trauma)

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What are the biochemical features of osteomalacia and Ricketts

High PTH
Low calcium and phosphate
Raised ALP

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Describe osteoporosis

Loss of bone mass, while the residual bone structure remains NORMAL

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What are the causes of osteoporosis

Lifestyle: Immobility/sedentary, smoking, EtOH, low BMI
Lack of oestrogen (e.g. menopause, anorexia nervosa)
Hyperthyroidism / thyrotoxicosis
Cushing’s syndrome or steroid use
Hyperprolactinaemia (inhibits FSH/LH/Oe)

Failure to attain peak bone mass due to childhood illness or early menopause increases risk of EARLIER fracture

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What are the clinical features of osteoporosis

Initial: fracture
- Neck of femur (NOF)
- vertebral
- Wrist (colle’s)

Otherwise asymptomatic

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What are the diagnostic markers of osteoporosis

NORMAL biochemistry

Dual energy x-ray absorptiometry (DEXA) of femoral neck and lumbar spine
Bone mineral density >2.5 SDs below the average value for a young health adult (T-score <-2.5)
Osteopenia = -2.5 < T-score < -1

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What is the management of osteoporosis

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Lifestyle:
- Weight-bearing exercise
- Stop smoking, reduced EtOH

Pharm:
- Vit D/Ca supplements
- Bisphophonates e.g. alendronate
- Teriparatide
- Oestrogens (HRT)
- Selective oestrogen receptor modulators (SERMs) e.g. raloxifene, tamoxifen)

What are the MOAs and SEs for bisphosphonates and SERMs

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bisphosphonates e.g. alendronate
Decreases bone resorption as it is much stronger and osteoclasts cannot turnover as quickly
BUT is highly irritative to the stomach
BUT they also bind calcium at the same time - so if taken with milk it would not be absorbed and be inactivated
Taken once a week with plenty of water and nothing else
IV zolendronate is becoming popular as it is only given once a year

SERMs
Tamoxifen - oestrogen antagonist for the breast (so does not increase breast Ca risk) and SERM for bone
BUT Worsens the symptoms of menopause

What are the symptoms of hypercalcaemia

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Polyuria/polydipsia (osmotic diuretic effect) + dehydration
Constipation (slows nerves/muscles)

Calcium >3.0mmol/L: Neuro - confusion/seizures/coma

What are the causes of hypercalcaemia

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PTH suppressed
- Malignancy
- Sarcoidosis
- vit D excess
- Thyrotoxicosis
- Thiazide diuretics
- Hypoadrenalism
- milk alkali syndrome (excess of Rennie sweet consumption)

PTH not suppressed
- Primary hyperparathyroidism (most common community cause of hyperCa)
- Familial hypocalciuric hypercalcaemia

What are the causes of primary hyperparathyroidism

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Parathyroid adenoma (80%)
Parathyroid hyperplasia
Parathyroid carcinoma (0/%)
MEN1 (adenoma) MEN2 (hyperplasia)

What are the clinical features of primary hyperparathyroidism

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BONES - PTH bone disease/pain, observe the wrist for Colle’s fractures
STONES - renal calculi
MOANS - abdominal pain due to constipation and pancreatitis
GROANS - psychiatric disturbance e.g. confusion
THRONES - polyuria

i.e. fractured bone, kidney stone, abdominal pain, confusion

What are the biochemical markers of primary hyperparathyroidism

Calcium - raised PTH - raised or inappropriately normal Phosphate - low urine calcium - high

Describe familial benign/hypocalciuric hypercalcaemia (FBH/FHH)

Mutation in CaSR which usually detects the level of Ca for the parathyroid gland This increases the set point for PTH release → mild hypercalcaemia Benign condition - do not form kidney stones + reduced urine calcium Gland removal will not cure it - surgery not required

What are the causes of Hypercalcaemia of malignancy

1. Humoral e.g. sq lung cancer releasing PTHrp → dissolves bone 2. Bone mets e.g. breast cancer causing local bone osteolysis (most common) 3. Haem. malignancy e.g. myeloma

How is hypercalcaemia managed

1. Fluid resus (pt will be dehydrated) - 0.9% saline 1L over the first 1-2 h - re-measure → 4-6L over 24h 2. Bisphosphonates if the cause is known to be cancer 3. Treat underlying cause e.g. surgery

What are the causes of hypocalcaemia

PTH driven (low PTH) Surgical e.g. post thyroidectomy Auto-immune hypoparathyroidism Congenital absence of parathyroids e.g. DiGeorge syndrome Mg deficiency (PTH regulation) non-PTH driven vitamin D deficiency - dietary, malabsorption, lack of sunlight CKD (1a-hydroxylase not produced → reduced Ca resorption → hypoCa → PTH stimulated → secondary hyperPTH → hyperCa → tertiary hyperPTH ) PTH resistance (pseudohypoparathyroidism)

What are the clinical features of hypocalcaemia

Neuro-muscular excitability - Chvosteks sign (fascial nerve excitability, twitching of facial muscles in response to tapping over the facial nerve – 29% sensitive) - Trousseaus sign (carpopedal spasm induced by pressure - latent tetany – 94% sensitive) - Hyperreflexia - Convulsions - Laryngeal spasm → stridor - Choked optic disk - Prolonged QT - Peri-oral paraesthesia

What is Paget's disease and what are the clinical features

Focal disorder of bone remodelling Features: - Focal pain - Warmth and tenderness over bone - Deformity e.g. bowing of tibia, skull enlargement, deafness (CNVIII involvement), kyphosis - Fracture e.g. fissure fracture - Malignancy - Cardiac failure

What are the diagnostic features of Paget's disease of the bone

ALP: raised Calcium: normal Phosphate normal PTH: normal Diagnosis is made via X-ray or nuclear medicine scan Pelvis, femur, skull, and tibia commonly affected

What is renal osteodystrophy

All skeletal changes resulting from chronic renal disease (osteitis fibrosa cytica, osteomalacia, osteosclerosis, growth retardation, osteoporosis) Secondary hyperparathyroidism and retention of aluminium from dialysis fluid Calcium: low Phosphate: high PTH: high (response to Ca) ALP: high

What is osteitis fibrosa cystica and what are the characteristic features

Hyperparathyroid bone disease due to hypocalcaemia reducing bone mineralisation and increasing resorption Shows subperiosteal erosions and brown tumours

What is the difference between T-score and Z-score for osteoporosis DEXA scans

○ T-score sd from mean of young healthy population, useful to determine fracture risk Z-score sd from mean of aged-matched control, useful to identify accelerated bone loss in younger patients

What are the levels of the following markers for each of these diseases: Calcium, phosphate, PTH, vit D, ALP Osteoporosis Osteomalacia/ricketts Paget's Parathyroid bone disease Renal bone disease

Osteoporosis: Everything normal Osteomalacia/ricketts: Ca low, Pho PTH high, vit D low, ALP high Paget's: ALP high, everything else normal Parathyroid bone disease: Ca high, Pho low, PTH high, vit D N, ALP N Renal bone disease: Ca low, Pho high, PTH high, vit D N/low, ALP high

What are the causes of secondary hyperparathyroidism

CKD (renal osteodystrophy) Vitamin D deficiency Malabsorption syndromes

What are the causes of tertiary hyperparathyroidism

Prolonged 2° hyperparathyroidism causing unregulated secretion of PTH Kidney transplant

Describe the clinical steps to understand the cause of hypercalcaemia

1. Albumin measurement Albumin low → measure urea - Urea low: cuffed specimen - Urea high: dehydration Albumin high → measure phosphate - Phosphate low: primary or tertiary hyperPTH Phosphate high → measure ALP ALP normal: myeloma, vit D excess, Sarcoidosis, milk alkali syndrome ALP high: Bone mets, thyrotoxicosis, sarcoidosis

What is the management for hypocalcaemia

symptomatic, Ca <1.875 → 10% Calcium gluconate IV Asymptomatic, mild → oral supplementation e.g. SandoCal Low vit D → vit D supplementation with alfacalcidol (CKD) or vit D2/D3

What are the hypocalcaemia differentiated by phosphate

HIGH PHOSPHATE CKD Hypoparathyroidism Pseudohypoparathryoidism Hypomagnesaemia LOW PHOSPHATE Osteomalacia Acute pancreatitis Overhydration Respiratory alkalosis

What are the risk factors for renal stones

Dehydration Abnormal urine pH e.g. meat intake, renal tubular acidosis Increased stone constituents excretion Urine infection

What are the causes of calcium stones

(most patients normocalcaemic) Hyperoxaluria (increased intake, absorption etc) Hypercalciuria (increased intake, renal leak)

What is the management (+investigations) for renal stones

1. Urgent CT (US for pregnancy, children, young people) 2. IM Diclofenac (analgesia) - Stones ≤5mm in diameter: Conservative management - Stones 6-20mm: Lithotripsy/Ureteroscopy - Stones >20mm: Percutaneous Nephrolithotomy

What is the appearance of the different type of renal stone on X-ray

Calcium mixed (most common): radio-opaque Calcium oxalate: radio-opaque Calcium phosphate: radio-opaque Triple phosphate "Struvite": Radio-opaque "Staghorn" Uric acid: radiolucent Cysteine: radio-opaque (light)

ChemPath - Calcium handling and metabolism Flashcards

(45 cards)