Calcium Phosphate Metabolism 2 Flashcards
Classic Hypercalcaemia case…
- 60yr old man with a 2 year history of tiredness
- One previous episode of haematuria
- No thirst, poluria, constipation, bone pain
NOTE: Calcium bound to albumin in the serum, if there’s a big change in serum Calcium that’ll change the serum Ca2+ levels
Moderately increased sCa<strong>2</strong>+ so you then check his PTH levels, as primary benign Hyperparathyroidism is the most common cause of Hypercalcaemia.
PTH 9.5pmol/L (2.5-7.5) Confirms diagnosis!
>95% of hypercalcaemia cases fall under one of these 4 causes!
- Primary hyperparathyroidism**** (excess PTH)
- Cancer-associated
- Vitamin D toxicity
- exogenous (tablets)
- endogenous (sarcoidosis)
- Familial Benign Hypercalcaemia (FBH)
****Most common!
Benign Primary Hyperparathyroidism
Usually a singular adenoma on 1 of the 4/5 PT glands, which is autonomously making PTH (and avoiding negative feedback no matter the sCa2+).
5-10% of the time all the glands are involved.
High Serum Ca2+, lower serum phosphate and normal-high PTH.
High urinary phosphate (decr. renal tubular reabsorption) and high urinary Ca2+(body trying to excrete excess)
Treatment: removal of adenoma!
What does this mans PTH levels tell us?
They are nearly undetectable, so he has non-PTH related Hypercalcaemia
When he checked PHrP it was much higher then it should’ve been.
Cancer-related hypercalcaemia, with a solid tumour secreting (PTHrP)
What types of cancer can give you hypercalcaemia?
- Solid Tumours secreting PTHrP
- carcinoma of the bronchus
- Multiple skeletal metastases
- advanced breast cancer
- Bone marrow malignancy: secretion of cytokines stimulating bone reasorption
- multiple myeloma
How does PTHrP cause hypercalcaemia
The same way PTH does, acts on;
BONE:
- PTHrP stimulates Ca2+ release → raises plasma calcium
KIDNEY
- PTHrP increases renal tubular reabsorption of Ca2+ → raises plasma calcium
- PTHrP decreases renal tubular reabsorption of phosphate → lowers plasma phosphate
Also acts on 1,25 (OH)2D and increased reabsorption in gut
Whats going on
Alkaline Phosphatase: made from liver and bone, but in this circumstance we would think it was all from bone! Marker of osteoblast functional bone formation. Charasteristic of coelic
High fat excretion in the stool → malabsorption
Unmineralised bone → osteomalacia (due to Ca2+ or phosphate deficiency)
She has Coeliacs disease: autoimmune disease causing villous atrophy and malabsorption
- Malabasorption of iron, folate, calcium, Vitamin D3
- Secondary hyperparathyroidism (compensatory but couln’t get to Ca or P for effective bone formation)
- Sunlight deficiency as not going out, accelerated metabolism of vit D via PTH, loss of dietary vit D
- Vitamin D deficiency
- Osteomalacia
Treatment: gluten free diet and Vit D supplements
Osteomalacia
Failure of bone to mineralise
A histological diagnosis, (accumulation of unmineralised pink-staining osteoid) but this is very invasive so sometimes use overwhelming evidence instead.
Deficiency in one or both of the minerals (Ca and Phosphate)
Osteomalacia in kids is rickets
Signs and symptoms of osteomalacia/rickets
- Bone pain
- Proximal myopathy
- fracture (soft, bendy, fragile bones)
Rickets;
- valgus/varus deformities
- prominents costochondral joints
- poor growth
What can cause low Vit D along the metabolism line?
- Inadequate exposure (frail, elderly)
- Low diet consumption
- Enzyme induction: some drugs speed up catabolsim
- Impaired 1a hydroxylase: advanced renal impairment stops conversion to bioactive form (stays at 25 (OH)D)
- GI disease: malabsorption
Pseudohypoparathyroidism
PTH resistance, not working properly.
Clue is in the clinical features, of 4th and 5th metacarpals.
Lots of PTH, but a mutation in one of the proteins that conducts the signal from PTH to cell stops the action. Usually in G<span>s</span><span>a </span>
Autosomal Dominant Hypercalciuric Hypocalcaemia (ADHH)
Abnormal activation of Calcium sensing Receptor (CaSR)
Usually sits on membrane of PT gland chief cells and reads ambient EC Ca levels.
And autosomal dominant mutation, so check parents to diagnose
Therefore the receptor reads Ca as much higher then it is, signals cells constantly → inappropriately low PTH secretion
also leads to low renal tubular reabsoption in the kidneys
Flip side of ADHH
The revers is BFH
The receptor isn’t working properly, detects abnormally low Ca levels → excessive PTH
Get mild hyperclacaemia
Treatment of ADHH
- No treatment required if asymptomatic
- hypercalciuria with nephrocalcinosis if treated with Vit D
- Small doses of Vit D if recurrent symptoms
Same with FHH, don’t get surgery from misdiagnosis!
- She has a complete fracture throught he right neck of the femur, explanation of pain.*
- Left hand side: shows crack in cortex, incomplete neck fractures.*
- Fracutres all over ramus, pelvis*
Low Phosphate and elevatedALP (marker of high bone turnover)
PTH high
Renal Phosphate handling shows high excretion even with low phospahte
Serum FGF-23 Phosphotonin was 8x the upper limit
SHe’s 80, so hypophosphotaemia is acquired.
Most likely is oncogenic osteomalacia: patients develop mesenchymal cell tumours which make and secrete FGF-23, causing phosphate wasting in kidneys, hypophosphataemia and osteomalacia.
Issue is finding the tumour, as often really small and attached to the skeleton! Find via MRI or CT, often in sinuses.
Vast majority of these tumours are benign; so if you find/safely remove symptoms slowly improve and no further treatment needed!
