10. Clinical chemistry CPC Flashcards
Case 1. Born 1939. 1991 (age 52). Depression. Councillor. Refused antidepressants. What alternative is available?
Alternatives include CBT. The patient started on St John’s wort.
What is St John’s wort similar to?
Paroxetine
How effective is St John’s wort?
moderately effective
What electrolyte imbalance is associated with depression?
Hypercalcaemia. Calcium, in general, affects the brain and nervous system
What happens in hypokalaemia?
Your myocardium becomes more an more irritable this leads to arrhythmias. As potassium rises, the myocardium becomes more and more stable, however, the ultimate stable rhythm is asystole. In other words, potassium causes asystole when it is very high, and VF when it is very low.
What does a Smith’s fracture look like? And when does it happen?
The radius has fractured forwards (i.e. towards the palm side). If you fall on a flexed wrist, it will cause a Smith fracture
What does a Colles fracture look like? And when does it happen?
• Falling on an outstretched hand causes a Colles fracture (the radius will then fracture backwards, away from the palm side)
What is a Pott’s fracture?
an ankle fracture that involves the tibia and fibula
How to treat Smith’s fracture?
Treated with manipulation under anaesthesia and plaster
Patient with hypercalcaemia and Smith’s fracture had depression which got worse. In 1992, the patient was admitted with severe abdominal pain. A urine dipstick is performed and is +++ blood. Why is this not glomerulonephritis or subacute bacterial endocarditis? What is it likely to be?
Glomerulonephritis is painless. Subacute bacterial endocarditis causes microscopic haematuria. This is likely to be renal stones.
What investigation for renal stones?
Plain abdominal x-rays will show calcified stones
Abdominal ultrasound is good for visualising nephrocalcinosis but…
takes longer to achieve.
Calcified gallstones and renal stones may look quite similar on …
a plain abdominal X-ray
Renal stones diagnosed. What should be done next?
Measure plasma calcium. Also do plasma PTH.
Is plasma calcium routinely measured when you send U&Es?
No
What is normal plasma calcium?
2.2 - 2.6 mmol/L
Differential diagnosis for hypercalcaemia:
Cancer, primary hyperparathyroidism (a lot of the time, patients tend to be quite well), sarcoidosis
How do you differentiate between the differential diagnoses for hypercalcaemia?
Plasma PTH
The patient with hypercalcaemia has a PTH of 3.0 (1.1 - 6.8 pM). What is the likely diagnosis?
If calcium is high then PTH should be suppressed. So, this patient has primary hyperparathyroidism. In hypercalcaemia of malignancy, PTH would be 0.
What is the prognosis of hypercalcaemia of malignancy?
Hypercalcaemia of malignancy has a near 100% 6-month mortality
What protein is important in foetal life?
PTHrP
Describe the mechanism of PTHrP
Important in foetal life. The placenta will release PTHrP which promotes an increase in calcium in the mother which can then be stolen by the baby to form a skeleton. PTHrP is also produced by the lactating breast. However, PTHrP if activated by cancer, can be really bad. PTHrP also stimulates cancer cells to invade bone.
Summarise the mechanisms of hypercalcaemia of malignancy
PTHrP, cancer invading the bone
What is the most common cause of primary hypercalcaemia?
Parathyroid adenoma (85%)
What is the mechanism for primary hypercalcaemia
- Parathyroid adenoma = 85% of causes of hypercalcaemia.
- Results in uncontrolled release of parathyroid hormone.
- This causes efflux of calcium from the bone + increased calcium reabsorption in the kidney + increased absorption of calcium in the intestines.
- PTH activates 1-alpha hydroxylase in the kidneys which activates vitamin D, which then increases absorption of calcium in the intestines
- PTH also promotes loss of phosphate (i.e. causes a low phosphate)
What are multiple parathyroid adenomas associated with?
MEN1
What are symptoms of hypercalcaemia?
Moans, bones, groans and stones. Many can be asymptomatic. Polydipsia/polyuria (due to nephrogenic DI). Calcium is effectively like mannitol, it carries water with it via osmosis
What are signs of hypercalcaemia?
Band keratopathy - calcium deposition across the front of the eye (feature of CHRONIC hypercalcaemia, cannot be hypercalcaemia of malignancy). Calcium stones are radio-opaque (but urate stones are radiolucent)
What are complications of hypercalcaemia?
Renal stones, pancreatitis, peptic ulcer disease, skeletal changes (osteitis fibrosa cystica)
What are risk factors for renal calcium stones?
Family history, dehydration, hypercalciuria (> 6 mmol Ca/day), hypercalcaemia, hyperparathyroidism
How may renal calcium stones present?
Pain, haematuria, recurrent infections (Proteus mirabilis loves calcium stones), renal failure
What are investigations for renal calcium stones?
CT-KUB, stone analysis, urine and serum biochemistry
What is the natural history of renal calcium stones?
Most stones will pass
What is the management of renal calcium stones?
Lithotripsy, cystoscopy, lithotomy
How can we prevent renal calcium stones?
Drink more water, treat hypercalciuria e.g. thiazides (loop diuretics do the opposite and make you lose calcium in the urine), treat hypercalcaemia
What needs to be done URGENTLY in the management of hypercalcaemia?
- IV access (venflon/central line)
- Catheter
- Rehydrate: 0.9% saline (can be litres)
- Initiate calciuresis: 0.9% saline Furosemide
- IV pamidronate 30-60 mg (hold off until desperate)
How much fluids does a person with hypercalcaemia need compared to a normal person?
Patient is DEHYDRATED. Normal person needs at least 3L over 24 hrs. Pts with hypercalcaemia need up to 6L over 24 hrs.
Why should too much fluids be given straight away to someone with hypercalcaemia?
In elderly patients, giving too much fluid too quickly could cause pulmonary oedema, so the patient should also be given furosemide to clear some space.
When should emergency management be done for hypercalcaemia?
If the calcium is > 3 mmol/L or the patient is very unwell (dehydrated, confused, drowsy, coma, seizures, renal failure). If it is < 2.8 mmol/L you can advise the patient to drink lots of water.
What is IV pamidronate and when should you give it in hypercalcaemia?
- IV pamidronate is a bisphosphonate that should only be used in desperate circumstances.
- They work by binding to bone and will have no effect for at least 1 week
- Bisphosphonates will form indestructible bone and it will push down calcium over a long time.
- Do NOT give bisphosphonates
- The diagnosis can become confusing after giving bisphosphonates because the calcium will fall -> secondary hyperparathyroidism
- Pamidronate is, however, very good at treating bone pain - it prevents invasion of bone by malignancy
What should be done at a leisurely pace in the treatment of hypercalcaemia?
Saline is safe when dealing with most conditions EXCEPT liver failure because liver failure patients RETAIN SALT (so you would prefer to use dextrose)
What should be done in non-emergency hypercalcaemia?
Keep well hydrate, avoid thiazides (they reduce hypercalciuria but increase plasma calcium), surgery - minimally invasive parathyroidectomy
When should a minimally invasive parathyroidectomy be done?
Technetium Sesta MIBI shows hyperactive parathyroid. An USS is also performed, and if the USS and the Sesta MIBI are concordant then the whole neck does NOT need to be opened. However, if they are not concordant, the surgeon will need to view all four glands and take out the largest one.
What will the X-ray of the hands in patients with primary hyperparathyroidism look like?
Often NORMAL, as time goes on, radial aspect will undergo cystic changes.
What does the histology of primary hyperparathyroidism look like?
Brown tumours are made up of multinucleate giant cells in the bone, the giant cells are activated osteoclasts, brown tumours are a feature of long-standing undiagnosed hyperparathyroidism.
CASE 2: 45 year old Afrocaribbean man presents with dyspnoea. What investigations should be done?
You are likely to do a CXR first, followed by an FBC. Other useful investigations: U&E, ECG and echocardiogram.
The CXR shows bilateral hilar lymphadenopathy, the histology of lymph nodes shows non-caseating granulomas and the calcium level is 2.82 (2.20-2.60). PTH is suppressed to undetectable levels. What is the diagnosis?
Sarcoidosis
What is the treatment for sarcoidosis?
Steroids are the mainstay of sarcoidosis treatment. It will normalise the calcium and treat the lung problem.
What is the mechanism of hypercalcaemia in sarcoidosis?
- Macrophages in the lungs express 1-alpha hydroxylase
- This will activate vitamin D
- Patients are more likely to become hypercalcaemic in the summer months because of increased exposure to sunlight
