ChemPath 1: Calcium Metabolism Flashcards
(72 cards)
1
Q
Why must the calcium in blood be fixed?
A
nerves, muscles rely on Ca for depolarisation
2
Q
What does Hypercalcaemia cause?
A
- failure of depolarisation –
- stones, bones, groans, moans + nephrogenic DI
3
Q
What does Hypocalcaemia cause?
A
- “trigger happy CNS” –
- epilepsy (aberrant firing of nerves and muscles) –
- CATS go numb
4
Q
What is the normal range of Ca in blood?
A
- Normal Ca = 2.2 - 2.6mmol/l
5
Q
What % of calcium is in serum?
A
1%
6
Q
Where is the rest of the Calcium in the body?
A
complexed with phosphate in bones and teeth
7
Q
What forms is the 1% of Ca in the serum in?
A
- Free, ionised calcium, biologically active –> 50% à maintain at a fixed level
- Protein-bound as albumin –> 40%
- Complexed with citrate/phosphate –> 10%
8
Q
What happens to the blood Ca levels if albumin is abnormal?
A
- An abnormal albumin affects the free calcium (e.g. in sepsis)
- If albumin is low…
- Bound calcium will be low, but free calcium is normal
- Corrected Ca refers to that (the corrected calcium can tell you what is wrong with albumin)
- So, if albumin = 30 and total Ca = 2.2
- Corrected Ca = 2.2 +(0.02 x 10) = 2.4mM
- So, corrected Ca shows if the problem is albumin, and that ionised Ca will be normal
9
Q
How might you overcome the abnormal Ca caused by abnormal albumin?
A
- “Corrected ca” reported by labs
- This compensates for albumin
- Serum Ca + 0.02 x (40 – serum albumin (g/l))
- In blood gas machines, ionised Ca can also be measured (around 1.1mmol/L)
10
Q
What is circulating Ca important for?
A
- Important for normal nerve, muscle function
11
Q
What happens in Chronic Ca deficiency?
A
- loss in Ca from bone to maintain circulating Ca
12
Q
Which organ detects hypoglycaemia?
A
- Hypocalcaemia is detected by parathyroid gland
13
Q
What are the actions of PTH?
A
14
Q
Which are the 2 key hormones involved in Ca homeostasis?
A
- PTH
- Vitamin D (steroid hormone)
15
Q
What are the 2 forms of vitamin D? What are they activated by?
A
- D3 → animal product, from sunlight hitting skin → cholecalciferol
- D2 → plants → ergocalciferol
- both activated by 1-alpha hydroxylase
16
Q
Describe the structure of PTH
A
84 aa protein
17
Q
How is vitamin D in the blood measured?
A
- Measurement = 25-OH Vitamin D3
18
Q
Where are the 2 forms of Vitamin D synthesised?
A
- Vitamin D3 is synthesised in the skin – cholecalciferol
- Vitamin D2 is a plant vitamin – ergocalciferol
19
Q
Name the organs in which Vitamin D is synthesised/processed etc and describe what happens at each
A
20
Q
Are vitamin D3 and D2 active?
A
yes
21
Q
Describe what happens to whether Vitamin D is active (or not) as it is processed in the body
A
- (SKIN) D3 → animal product, from sunlight hitting skin → cholecalciferol;
(INTAKE) D2 → plants → ergocalciferol
= ACTIVE - (LIVER) 25-hydroxylase –> 25-hydroxy-Vitamin D3
= INACTIVE - (KIDNEY) 1α hydroxylase –> 1,25-dihydroxy Vitamin D3
= ACTIVE
22
Q
Which enzyme hydoxylates Vitamin D3 and D2 in the liver?
A
25 hydroxylase
23
Q
Which enzyme hydroxylates 25-hydroxy-vitamin D3 in the kidneys?
A
1α hydroxylase
24
Q
Where can 1α hydroxylase also be expressed (other than the kidneys)?
A
- Rarely, this enzyme is expressed in lung cells of sarcoid tissue
- Sarcoid = causes hypercalcemia (seasonal) – summer hypercalcemia
- In sunlight, calcium goes up (more vitamin D activation
25
What is another name for 25-hydroxy-Vitamin D3?
calcidiol (prior to 1a hydroxylation in the kidneys)
26
What is another name for 1,25-dihydroxy-Vitamin D3?
27
What is the role of Role of 1,25 (OH)2 Vitamin D (Calcitriol)?
* Intestinal Ca2+ absorption and intestinal phosphate absorption
* Critical for bone formation (with osteoblasts)
* Other physiological effects
* Vitamin D receptor controls many genes – cell proliferation, immune system
* Vitamin D deficiency associated with cancer, autoimmune disease, metabolic syndrome
28
What is the cause of rickets/osteomalacia?
* Vitamin D deficiency
29
What is the cause of osteoporosis?
lack of oestrogen
30
What does Vit D deficiency cause?
* Defective bone mineralisation
* Childhood → rickets; Adults → osteomalacia
31
Describe the epidemiology of Vitamin D deficiency in the UK
* More than 50% adults have insufficient vitamin D
* 16% have severe deficiency during winter and spring
32
What are the risk factors for Vit D deficiency?
* Lack of sunlight exposure
* Dietary
* Dark skin
* Malabsorption
33
What are the clinical features of Osteomalacia?
* Bone and muscle pain
* Increase fracture risk
* Looser’s zones (pseudo fractures)
34
What is the biochemistry seen in osteomalacia?
Bio-chem →
* low Ca2+ and phosphate
* raised ALP
35
What are the clinical feautures of rickets?
* Bowed legs
* Costochondral swelling
* Widened epiphyses at the wrists
* Myopathy (weak muscles)
36
What is the cause of the features of osteomalacia?
lack of Ca
37
What are the clinical features of osteomalacia?
* Bone is demineralised
* Caused by vitamin D deficiency
* Renal failure
* Anticonvulsants induce breakdown of Vitamin D (phenytoin)
* Lack of sunlight
* Chappatis – phytic acid (cause osteomalacia)
38
What is the first clinical feature of osteoporosis?
* pathological fracture (asymptomatic until then)
* *(more common as you age, bone lost slowly after 20)*
39
What is the pathogenesis of osteoporosis?
* **Loss of bone mass, (**Reduction in bone density)
* but residual bone **normal in structure (**normal mineralisation)
40
What happens to the biochemistry in osteoporosis?
**all normal**
* Osteoporosis has bone loss but with a **normal calcium**
41
How is osteoporosis diagnosed?
* **DEXA scan** (Dual energy X-ray absorptiometry):
42
Where are the common sites of fractures in osteoporosis?
* Hip (femoral neck)
* lumbar spine
43
Explain T scores and Z scores
* T score – SD from mean of young healthy population – determine fracture (#) risk
* Z score – SD from mean of age-matched control – identify accelerated bone loss in younger people
44
What are the diagnostic values for osteoporosis and osteopenia? (T scores)
* Osteoporosis – T score
* Osteopenia – T score -1 and -2.5
45
What is the Tx for osteoporosis?
* Lifestyle
* Weight bearing exercise
* Stop smoking
* Reduce ETOH
* Drugs
* Vitamin D/Ca
* Bisphosphonates (alendronate) – decrease bone resorption – osteonecrosis of jaw
* Teriparatide – PTH derivative – anabolic
* Strontium – anabolic + anti-resorptive
* Oestrogens – HRT
* SERMs (oestrogen-like drug) – raloxifene (like Tamoxifen)
* Denosumab – biologic anti-RANK-L antibody
46
What are the symptoms of hypercalcaemia?
* Polyuria or polydipsia
* Bones
* Stones
* Abdo - constipation
* Neuro – confusion, seizures, coma
* Unlikely unless Ca \>3mmol/L (2.2-2.6)
Overlap with symptoms of hyperPTH
47
What qs must be asked when bloods come back as hypercalcaemia?
* First Q: is it a genuine result (repeat)
* 2nd Q: what is the PTH?
48
What can a high albumin in bloods mean in hypercalcaemia?
* High albumin = artificially elevated Ca
49
What is secondary hyperparathyroidism associated with?
2nd HPT is associated with a LOW calcium due to low vitamin D
50
What is the commonest cause of hypercalcaemia?
Primary Hyperparathyroidism
51
What are some causes of primary hyperparathyroidism?
* Parathyroid adenoma (80%)
* Hyperplasia
* *associated with MEN1, 2a*
* Malignancy of the parathyroid gland (carcinoma)
52
sWhat blood results will be seen in hypercalcaemia due to primary hyperparathyroidism?
* High serum Ca
* Low serum phosphate
* High PTH - inappropriate
* High urine Ca due to hypercalcemia
53
What blood results will be seen in hypercalcaemia due to malignancy elsewhere in the body?
* High serum Ca
* Low serum phosphate
* Low serum PTH – appropriate
54
What different presentations may a patient with primary hyperparathyroidism present with?
bones, urinary stones, abdo moans, psychiatric groans
55
Which organs have Ca-sensing receptors?
* **Parathyroid** – regulate PTH
* **Renal** – influences Ca resorption – PTH independent
56
What is Familial hypocalciuric hypercalcemia?
* Calcium Sensing Receptors mutation
* Reduced sensitivity to calcium
* Higher set point for PTH release
57
What bloods and urine results are seen in Familial hypocalciuric hypercalcemia?
* Mild hypercalcaemia
* Reduced urine Ca
58
What are the 3 causes of hypercalcaemia seen in malignancy?
1. **Humoral** hypercalcaemia of malignancy – **squamous cell lung cancer**
1. PTHrP released
2. **Bone mets** – e.g. in breast ca
1. Local bone osteolysis
3. **Haematological malignancy** – myeloma
1. Cytokines
59
What are some other causes of non-PTH driven hypercalcaemia ?
* **Sarcoidosis** – non renal 1α hydroxylation
* **Thyrotoxicosis** – thyroxine leads to bone resorption
* **Hypoadrenalism** – renal Ca transport
* **Thiazide diuretics** – renal Ca transport
* **Excess vitamin D** – sunbeds
60
What is the Tx for hypercalcaemia?
* **FLUIDS** (0.9% saline, 1L/hour and reassess)
* Treat underlying cause
* Cinacalcet acid – activates Ca sensing receptors
61
What are the signs & symptoms of hypocalcaemia?
* Neuromuscular excitability --\> Chvostek’s sign (face), Trousseau’s sign, hyperreflexia
* Convulsions
62
What must be done when diagnosing hypocalcaemia?
* 1st --\> repeat bloods and adjust for albumin (as the albumin can bind ionised calcium) - i.e. is the hypocalcaemia a genuine result?
* 2nd --\> what is the PTH?
63
What are the non-PTH driven causes of hypocalcaemia?
64
What are the PTH-driven (due to low PTH) causes of hypocalcaemia?
65
Which has the lowest calcium out of:
* primary HPT
* secondary HPT
* osteoporosis
* Paget’s
* breast cancer
secondary HPT
66
What is Paget's disease?
focal disorder of bone remodelling
67
What are the signs and symptoms of Paget's disease?
* Bone pain
* Warmth
* Cardiac failure
* Deformity
* Fracture
* Malignancy
* Compression (blindness, deafness)
## Footnote
*Commonly affected bones: Pelvis, femur, skull and tibia*
68
What are the bloods seen in Paget's disease?
* Elevated alkaline phosphatase
* Ca and PO4 are NORMAL as…
* Osteoclasts and blasts are both active together
69
What imaging is conducted in ?Paget's disease?
* Nuclear med scan / XR
70
What is the Tx of Paget's disease?
* Bisphosphonates for pain
71
What:
* Ca
* phosphate
* PTH
* Alk Phos
* Vit D
is seen in the following conditions?
72
What are some other metabolic bone disorders?
* **renal osteodystrophy**
* due to secondary HPT + retention of aluminuim from dialysis fluid
* **osteistis cysitica**
* in primary HPT, loss of cortical bone --\> fracture risk
## Footnote
*both are quite rare due to modern Tx of underlying cause*
