Complete run through of the MRCP Part I – Day 3 of 40

Page 85 isn’t in MRCP Part I, so I’ll split page 84 over two days.



SVC Obstruction

Neutropenic Sepsis


The normal corrected calcium is about 2.25-2.5 mmol/litre, though use your local lab.

Calcium is roughly 50% bound to albumin. Uncorrected calcium levels assume a normal amount of albumin. If albumin is abnormal, the point of correcting for this is to see what the total calcium levels would have been if the albumin were normal.

To correct for albumin: Add 0.1 mmol/litre to calcium concentration for every 4 g/litre that albumin is below 40 g/litre and a similar subtraction for raised albumin


Uncorrected Calcium = 2.1 mmol/litre

Albumin = 32g/litre

Therefore 0.2mmol/litre should be added to the uncorrected calcium to correct it.

Corrected calcium =2.3 mmol/litre

Most labs do this automatically.

Effects of hypercalcemia (from Patient UK):

Patient Uk Hypercalcemia

“Stones, bones, moans and groans” generally refers to long standing hypercalcemia, especially the stones bit. You get this more in hyperparathyroidism than malignancy.


Firstly, a long touriniquet time whilst drawing the sample can elevate calcium.

If the hypercalcemia is genuine, the most common two causes are hyperparathyroidism and malignancy.

Hyperparathyroidism causes increased calcium absorption. Increased PTH also results in increased calcium reabsorbtion at the distal tubule.

Usually this is caused by an adenoma, which may retain some degree of negative feedback from the elevated calcium level. If this is the case, then there were be a subtle, long standing hypercalcemia. If the feedback is lost e.g.carcinoma, then the presentation may be of more symptomatic hypercalcemia.

Hypercalcemia in malignancy is caused by 1) increased osteoclastic activity within bone from osteolytic mets and/or 2) PTH-related peptide e.g. breast cancer, squamous cell lung cancer. It progressively worsens until it is treated, unlike the majority of hyperparathyroid cases which tend to reach a steady state.

Granulomatous diseases like TB and sarcoid causes excess vitamin D to beproduced by the excited macrophages, leading to hypercalcemia.

Endocrine causes include thyrotoxicosis, phaemochromocytoma and adrenal insufficiency.  I don’t know the mechanism.

Iatrogenic causes include vitamin D and thiazide diuretics.

Finally, the weird. This includes milk alkali syndrome, tertiary hyperparathyroidism (when you’ve had secondary hyperparathyroidism for so long that the gland starts secreting PTH without stimulation) and familial hypocalciuric hypercalcaemia.

What does parathyroid hormone do again?

Three end organs:

Kidney – increases absorption of calcium and loss of phosphate in the distal tubule. Also stimulates hydroxylation of vitamin D

Gut – increases absorbtion of calcium (via vitamin D)

Bone – increases osteoclastic absorption of bone

And vitamin D?

Mostly helps with calcium (and to a lesser extent, magnesium and phosphate) absorption from the gut. It also maintains mineralisation of the bone and stimulates the differentiation of osteoclasts, although that last effect is not very physiologically significant. It also negatively feedbacks on PTH secretion.

How can we use phosphate levels to work out the cause of hypercalemia?

These are decreased in PTH excess and often in malignancy. They are usually increased in vitamin D excess.

And alkaline phosphatase?

High in bony mets. Low in vitamin D excess. Otherwise usually normal.

So how do we treat hypercalcemia?

If you have somewhat functional kidneys, then excess calcium should normally  be filtered out. By infusing the patient with lots of saline, this will dilute the calcium and also promote renal excretion.

No treatments work as well in the acute phase as generous volumes of saline in a patient with decent kidneys. This is just using the body’s own calcium removal system.

If the patient has end stage renal failure, dialysis will be necessary.

Then what?

Furosemide has its fans. It increases renal calcium clearance and can help with fluid overload. A thiazide diuretic would make things worse.

Fun fact: Furosemide is called Lasix in the US because its half life is 6 hours; it lasts for six hours = Lasix.

Bisphosphonates can take at least 24 hours to have a decent effect, so are second line.

SVC obstruction

An old question I wrote:

How does it present?

Patient UK:

1. The onset may be gradual or acute, depending on how quickly the condition proceeds from partial to complete obstruction and the degree of development of a collateral circulation

2. Symptoms tend to be aggravated by postures which increase the venous pressure in the upper part of the body, such as bending over or lying down.


Early in the clinical course of superior vena cava (SVC) syndrome (SVCS), few, if any, signs or symptoms may be observed. Typically, symptoms accelerate as the underlying malignancy increases in size and/or invasiveness. Dyspnea is the most common symptom, followed by trunk or extremity swelling. Other symptoms include the following:

  • Facial swelling
  • Cough
  • Orthopnea
  • Headache
  • Nasal stuffiness
  • Light-headedness

Neurologic symptoms, such as dizziness and confusion, are late findings as cerebral edema occurs.

You may see jugular venous distension and facial engorgement, as well as hear stridor. Signs get more pronounced if the arms are raised. The JVP may be non-pulsatile.


Malignancy account for the majority of cases. Bronchial carcinoma accounts for 80% of all cases, and lymphomas for 15%. There can also be catheter and pacemaker related thrombosis.

It is mostly a clinical diagnosis. However, plain radiography may show a mediastinal mass. CT scanning is super definitive, and invasive contrast venography may be used prior to surgery.


Unless there is airway compromise or cerebral edema, it is worth hunting down the specific cause before embarking on treatment, as the ideal treatment will depend on the cause. You have time.

Simply elevating the patient’s head can decrease the hydrostatic pressure and therefore the edema. Patients will often be started on diuretics and high dose dexamethasone whilst awaiting more definitive treatment.

Chemotherapy is best for small cell cancers and lymphoma.

Radiotherapy may be used for cancers unresponsive to chemotherapy, or if attempts to make a tissue diagnosis have been unsuccessful.

Stents can provide more rapid relief than radiotherapy or chemotherapy (within 72 hours). There is a risk of restenosis. Surgical bypass is possible if the patient is fit enough.

Clots are treated with anticoagulation or even thrombolysis, depending on the severity of symptoms.

Neutropenic sepsis

Who gets it?

Mostly patients receiving chemotherapy, about 7-10 days after a session. Bleomycin and vincristine tend not to cause bone marrow suppression, but other chemotherapies do. Neutrophils have a peripheral half life of 5.4 days  so it takes a while to reach neutropenic levels after the bone marrow has been suppressed.

It can also occur with any cause of bone marrow suppression.

What is neutropenia?

The BNF defines it as less than 1.0x 10^9 neutrophils per litre.

What is neutropenic sepsis?

NICE says:

Diagnose neutropenic sepsis in patients having anticancer treatment whose neutrophil count is 0.5×109 per litre or lower and who have either:

  • a temperature higher than 38°C or
  • other signs or symptoms consistent with clinically significant sepsis.

This 0.5/1.0 discrepancy confuses me. I have emailed our hospital’s haematologists for their thoughts and will post them here when I get a reply. What is clear is that the lower the neutrophil count, the more significant the neutropenia.

The signs of sepsis may be masked in neutropenia, so have a high index of suspicion.


Culture everything, and ask the lab to also consider fungal things.

That means 2 sets of blood cultures, ideally 10 mins apart, and cultures off every line going. Sputum, urine, stool, skin/wound…if you can see it, culture it.

Also send FBC (!), CRP U&E, DIC screening, lactate, CXR and then what you see fit. This may include PCR for various viruses for example.

Risk Assessment

There is a tool NICE suggest is used to risk assess patients as high or low risk. Low risk are those scoring 21 or more on this tool. Mortality varies according to the MASCC prognostic index: as low as 3% if the MASCC score is >21, but as high as 36% if the MASCC score is <15.


Get broad spectrum antibiotics in there within 1 hour.

NICE says to give all patients who merit IV antibiotics (high riskers and some low riskers) tazobactam and piperacillin. Add on vancomycin if MRSA. Add on macrolide if pneumonia suspected. Hardly ever add gentamicin unless there’s a really, really good reason.

If it’s not responding after 48 hours, you might need to add an antifungal. This is well into the microbiology/haematology/oncology specialist territory. Walk backwards slowly, maintaining eye contact and your winning smile.

Some low riskers can get away with oral antibiotics. Obviously someone else will decide this.


Overall mortality rates are ∼5% in patients with solid tumours and as high as 11% in some haematological malignancies. Prognosis is worst in patients with proven bacteraemia, with mortality rates of 18% in Gram-negative and 5% in Gram-positive bacteraemia.

Over the last few decades a shift has occurred from Gram-negative bacteria to Gram-positive organisms.


For adult patients (aged 18 years and older) with acute leukaemias, stem cell transplants or solid tumours in whom significant neutropenia (neutrophil count 0.5×109 per litre or lower) is an anticipated consequence of chemotherapy, offer prophylaxis with a fluoroquinolone during the expected period of neutropenia only.

(Says NICE.)

That took a while. Sleep now do.


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