Focused MRCP run through – introduction

Change of plan.

I’ve been working through past questions on and the Medical Masterclass series. It doesn’t seem like listing everything in the syllabus is the most efficient way of covering this. There will be lots of repetition, and I’m not sure it helps to have huge posts every day. Instead, I’m going to complete one revision of everything on my own, and then put the key facts/concepts that were most useful up on this blog. The finished product will be far more selective, a bit like but with more emphasis on explanation.

Will post here very soon!


Complete run through of the MRCP Part I – Day 4 of 40

This page involves going through 8 types of cancer. I’ll try my best to cover them over the weekend.

Breast cancer

What is the breast?

The breast mostly consists of fat, lobes and ducts. The fat provided some breathing space between the lobes. The lobes are where the milk is made, under the stimulation of prolactin. The lobes drain into ducts, which meet up and drain into the nipple.

Ductal carcinoma accounts for 70% of breast cancer, and the rest is mostly lobular carcinoma.

Risk factors


Family predisposition occurs in 5-10% of breast cancers, which includes the famous BRCA 1 and 2.

BRCA1 carriers have a lifetime risk of 80% for breast cancer and 60% for ovarian cancer.
BRCA2 carriers have a lifetime risk of 80% for breast cancer and 27% for ovarian cancer.

It’s the men who get more screwed by BRCA2 though – 5% of men will get breast cancer, and 6-14% prostate cancer.

Other risk factors

Ostrogen exposure is what you don’t want. In other words, have a late menarche, an early menopause and multiple teenage pregnancies and you should be fine. The role of the COCP is controversial.

It is still the most common non skin cancer in women in the UK, but no longer the most common cause of death from cancer for British women. That distinction now goes to lung cancer.


Increasingly, women now present from screening. Usually a mass that persists throughout the menstrual cycle. Less than 10% complain of nipple discharge, and pain in even less. Rarely, you get late neglected presentations from old ladies, or symptoms of mets and systemic features. Paget’s disease presents as eczematous change in the nipple with itching, burning, oozing or bleeding. Inflammatory lung cancer is rare in the UK (1-2%), but seems to be higher in Africa.

On examination, the malignant lump is hard, tethered with irregular margins and usually painless. There may be skin dimpling and a bloody, unilateral discharge.

The main sites for mets are BLBL: bone, lung, brain, liver.


Younger patients (<35 years) with more dense breasts do better with ultrasound, whereas mammography is more suitable as breasts become less dense.

For the purpose of the screening programme, if there are no symptoms of breast disease then a mammography is all that is done.

For the investigation of a suspicious lump, triple assessment is usually done. This involves imaging, clinical exam and biopsy (fine needle or core biopsy).

The decision to proceed to biopsy may be determined by what the imaging showed. For example, a simple cyst may be just aspirated, but a complex cyst may need biopsy. Remember, fine needle has a smaller needle but doesn’t give you the tissue architecture or histology.

A Simplified Approach to Staging

T1 <2cm
T2 2-5cm
T3 5cm +
T4 fixed to chest wall, including peau d’orange

N1 – auxillary lymph nodes and mobile
N2 – auxillary lymph nodes and fixed OR internal mammary lymph nodes on their own
N3 – both of the N2ers (ie auxillary lymph nodes AND internal mammary lymph nodes) OR any lymph nodes around the clavicle (supra or infra)

M0 – not mets
M1 – mets

The most clinically important divide in the staging is Stage IIIA and Stage IIIB, as this determines early or late. The way I remember this is that Stage IIIB is anything with T4, IIIC is anything with N3, and IV is anything with M1. If you haven’t got any of those things, you are probably early stage.

Early treatment

Standard practice with wide local excision, with adjudvant radiotherapy. The sentinel lymph node is usually biopsied at surgery.

If the axillary nodes are clear, then opinion is divided on who gets adjuvant chemotherapy. Generally, expressing hormone receptors is a good thing; it means the cells are somewhat differentiated. Those with small, ER-positive tumours may get away without adjuvant chemotherapy in this group.

If the nodes are positive, then chemotherapy plus luteinising hormone release hormone analogue (e.g  goserelin, just like prostate cancer) or tamoxifen is given. The exception to this is premenopausal women with ER-negative tumour, who don’t get the goserelin equivalent or tamoxifen.

In addition to this, if the tumour is HER2 positive, trastuzumab is added.

Advanced breast cancer

If there are mets, then the aim is generally to palliate bony mets with bisphosphates, and maybe add on aromatase inhibitors. Aromatase inhibitors are only of benefit in post menopausal women, as they inhibit the production of estrogens from steroids, and in premenopausal wowen there’s an estrogen factory that produces volumes of estrogens that dwarf those produced by steroid conversion.


Tamoxifen is a selective ER modulator and can induce menopausal symptoms. The famous side effect is the risk of endometrial polyps and cancer. It is beneficial against osteoporosis.

DEXA scans

Breast cancer treatments induce osteoporosis by being anti estorgen. If giving aromatase inhibitors, or suppressing the ovaries, then get a baseline DEXA.

But there’s more to treatment than that…

Yup – see the NICE guidance. I’ve just tried to summarise this plus a few other sources in the least confusing way I could.


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.

Complete run through of the MRCP Part I – Day 2 of 40

Wow. This is a long syllabus. It’s taken me three hours to put this next section together, which leaves me with little time for pretty pictures/mnemonics. Let’s crack page 83.


Occupational asthma

This accounts for one sixth of all cases of asthma. Forget asbestosis, silicosis or smelly mould fancier’s lung – occupational asthma is the most common occupational lung disease.

Common allergens include flour, grain, wood dust, animal bits and isocyanates.

The history is more useful for excluding occupational asthma rather than confirming it i.e. if you have symptoms which are worse at home then at work, you don’t have occupational asthma. However, if your symptoms are worse at work, you may or may not have occupational asthma.

To be sure, you need to do confirm a relationship between asthma and work exposure by performing Serial measurements of PEFR at home and at work. Measurements should be made every two hours from waking to sleeping for four weeks, keeping treatment constant and documenting times at work.

Rhinitis and asthma often co-exist, including when occupational.

Once the relationship is confirmed, the patient must not work in that environment. At all.


Other common allergies

1. Latex allergy

Affects medical workers, people with spina bifida and rubber workers. The allergen is either natural or synthetic rubber

Remember the fruit latex syndrome in 30-50% of those with latex allergy. This involves allergy to avocado, banana, chestnut, kiwi, peach, tomato, potato and bell pepper.

2. Insect strings 

Usually bee and wasp stings

3. Drug allergy

I had no idea there was guidance specifically for drug allergy – see

MRCPwise, it’s probably worth going through the table of Type I – IV hypersensitivities on page 45. The guidance tells you about risk factors for developing allergies as well as how to test for allergy semi-safely.

I also learnt from this guidance that intradermal tests are more sensitive but less specific than skin patch tests, and have a higher risk of causing anaphylaxis.

4. Food allergy

The Medical Masterclass focuses on nut allergies, which are the commonest food allergies. Peanuts account for >50% of all food allergies.

In children, failure to thrive, vomiting and eczema can all be explained by food allergy.

Distinguishing between intolerance and allergy can be tricky. Allergy happens within seconds of ingestion, and only minute quantities are needed. In contrast, intolerances take hours to develop, and a small quantity poses no problem.

Intolerance e.g. lactose intolerance produces bloating and diarrhoea. Allergies may provoke eczema, reflux, GORD as well as anaphylaxis.

A food diary, combined with skin prick testing/appropriate IgE tests can be helpful.


Angioedema and urticaria

I found the patient information to the British Association of Dermatologists helpful:

The weals of urticaria may be flesh-coloured, pink or red. They can be of different shapes and sizes, but usually look like nettle stings. An important feature of urticaria is that although the rash may persist for weeks, individual lesions usually disappear within a day, and often last only a matter of hours. However, they sometimes leave bruising especially in children. New weals may then appear in other areas. In ordinary urticaria, the weals can occur anywhere on the body, at any time.

The deeper swellings of angioedema occur most frequently on the eyelids, lips and sometimes in the mouth, but they may occur anywhere. They are not usually itchy, and tend to settle within a few days. If the hands and feet are affected, they may feel tight and painful.

Angioedema occurs beneath the dermis and affects the skin and mucosa, whereas urticarial occurs above the dermis and only affects the skin. Angioedema is painful and tense; urticarial is itchy.

Almost any medicine can cause ‘acute’ urticaria, but painkillers (especially aspirin and medicines like ibuprofen), antibiotics (especially penicillins) and vaccinations are most likely to be responsible. Angioedema, in particular, can be caused by a type of drug (ACE inhibitors) used to treat high blood pressure.

Where does C1 esterase deficiency come into it?

Hereditary angioedema causes provoked or unprovoked attacks lasting 2-5 days of laryngeal odema, subcutaneous swelling and abdominal pain. The tests you want initially is C4 level and if this is low, then C1 INH function and level of protein.

What about ACE inhibitors?

Any individual can get angioedema from ACE inhibitors, though it is more common in Afro-Carribeans. It can occur years after uneventful ACE inhibitor use, and is poorly responsive to antihistamines, corticosteroids or adrenaline. The episodes may persist for some months after stopping the ACE inhibitor. Switching to ARBs is usually successful.

What is the management of angioedema?

See In general, the acute attack usually needs nothing, although if there is airway compromise then manage as anaphylaxis. Chronic angioedema should be started with an antihistamine, although antihistamines don’t always work in angioedema.

And urticaria? 

First line is a non sedatating H1 antihistamine e.g. cetirizine plus three days of 50mg prednisolone.


Allergen sensitisation…

Step 1: Choose an allergen

Step 2: Get a B-cell to get excited by this allergen

Step 3: Invite this B-cell to mature into a plasma cell and secrete IgE specific to this antigen

Step 4: Stick the IgEs onto mast cells

You have now sensitized the patient!

Primary prevention of allergy prevents this sensitization from happening. This means allergen avoidance.

Secondary avoidance means preventing further sensitization once the process has started. This means leaving the job which triggers occupational asthma.

…and immunotherapy


  1. Hay fever that cannot be controlled with the usual management (unless asthmatic)
    To manage hay fever needs allergen avoidance, education and meds. Avoidance needs knowledge of the allergen, which can be found by skin prick tests
    Topical antihistamines for nasal symptoms are great, but only tackle nasal symptoms. Topical intranasal steroids are safe long term and more effective, but risk dryness, crusting and bleeding.
    Oral antihistamines are the mainstay, and work on neutrally mediated itch, sneezing and rhinorrhea. They don’t cover the blocked nose as well as intranasal steroids however.
    There are also nasal decongestants, and eye drops eg sodium cromoglicate

  2. Hypersensitivity to wasp and bee venom

What happens?

Administer gradually increasing quantities of specific allergens to patients with IgE-mediated conditions until a dose is reached that is effective in reducing disease severity from natural exposure.

How does it work?

Eventually, the allergen stimulates IgG rather than IgE production.


ACE inhibitors – they may trigger an anaphlyactoid reaction (anaphylactoid is basically anaphylaxis that is not IgE mediated)

Beta blockers – reduce the efficacy of adrenaline, which may be needed


Allergen avoidance

The main allergens are house dust mite, mould, pollen, pets and dust. Advice on avoidance is given at


Natural history of allergic diseases

Asthma stops in about 55% of children by the time they reach adulthood. This is more likely the earlier the asthma started.

Eczema stops in around a third of children when they reach adulthood.

Rhinitis tends to persist into adulthood.

There is a concept called the ‘allergic march’ – see


The tests

The skin prick test needs resuscitation facilities to hand, but is most useful for food allergy and rhinitis (include tree pollen, grass and weed)

Not great if: dark skin, dermatitis, dermatographism, unable to stop antihistamines for 48 hours before

Allergens introduced to skin through pricking. If positive, a wheal of at least 2/3mm develops. Negative predictive value is 95%, but positive predictive value is only 50%, which means a good history makes a big difference.

A skin test for A. fumigatus is done for ABPA, as well as total IgE.

RAST and ELISA are blood tests looking for specific IgEs. They are expensive, but are not affected by antihistamines or the condition of the skin.

Oral food challenge is the definitive but risky test for food allergy.

Patch testing – read at 48-72 hours, and is used for contact dermatitis and Type IV stuff in general.

Lactose intolerance is tested by the Lactose hydrogen breath test:

The patient ingests a standardised amount of lactose (2 g/kg, maximum 25 g) after an overnight fast with measurement of exhaled hydrogen over a 2- to 3-hour period. A positive test is an increase of >20 ppm of exhaled hydrogen after approximately 60 minutes. (BMJ Learning)

Complete run through of the MRCP Part I – Day 1 of 40

The MRCP Part I has a syllabus, which consists of pages 82 to 121 of this document.

That’s 41 pages, and the exam is on 10th September 2013.

Going at just over a page a day for the next 40ish days, I’ll find out about each topic and then summarise them as a blog post, and throw in some SBAs.

I’m totally relying on this, so I can assure you it’s in my interests to be as comprehensive yet memorable as possible.

The syllabus has three knowledge levels:

A Establishing a diagnosis

B Establishing a diagnosis
 and Knowledge of relevant investigations

C Establishing a diagnosis
 and Knowledge of relevant investigations and management and Knowledge of prognosis and likely response to therapy

Let’s start at page 82:

Anaphylaxis (Level C)


A severe, life threatening, generalised or systemic hypersensitivity reaction

The  pathology:

Usually this involves an allergen binding to some IgE that is itself bound to mast cells or basophils. When the IgE is bound, inflammatory mediators are released from mast cells or basophils. This includes histamine, amongst others. Histamine and other inflammatory mediators cause vasodilation, oedema and increased capillary permeability.


1. Insect stings, especially bee and wasp.

2. Lots of foods, especially nuts (peanuts account for >50% of food related anaphylaxis).

3. Medication wise, antibiotics, NSAIDs, muscle relaxants and aspirin are the most commonly involved.

4. Contrast agents.To establish a diagnosis:

According to the ALS course, anaphylaxis is likely if a patient who is exposed to a trigger:

1. develops a sudden illness which rapidly progresses


2. with skin changes (flushing, urticarial, angioedema)


3. life threatening ABC problems

Q. How do you distinguish simple urticaria from anaphylaxis?

A. The presence or absence of life threatening ABC problems. Also bear in mind that up to 20% of anaphylaxis cases will have minimal or absent skin changes.

Q. What exactly does urticaria look like?

A. See


Tips for treatment:


The position you put the patient in depends on what is going to kill them first. If they are massively hypotensive, consider lying them flat and raising the legs. If they are short of breath, they may prefer sitting up. Unconscious but breathing patients should be placed in the recovery position.

Fluid choice

Cystalloids are preferred, as there is a risk of further anaphylaxis with colloids.

IM injection site

The best site is the anterolateral aspect of the middle third of the thighs.

Cardiac Arrest

If cardiac arrest occurs after anaphylaxis, start normal ALS. In addition, consider steroids, antihistamines and large volumes of fluids.


Don’t mess around unless you are experienced. You can worsen laryngeal edema with ham fisted intubation attempts. Intubation becomes more and more difficult as time progresses, so ask a senior anaesthetist to consider early intubation.


These only take place once the patient is stable.

Mast cell tryptase taken:

1. As soon as possible after the patient is stable
2. 1-2 hours after symtoms began
3. 24 hours or later for a baselines


Observe all patients for at least 6 hours, and sometimes longer for high risk patients e.g. asthma, previous biphasic response. Continue steroids and antihistamines for 3 days, and educate the patient about EpiPen use.

Interesting facts:

The risk of death is increased in asthmatics. You may need to start treating asthmatic patients with anaphylaxis for asthma concurrently.

If an untreated patient hasn’t died within six hours of the exposure, it probably is not anaphylaxis. Food allergy takes about 30 minutes to kill, insect stings about 15 minutes and IV meds less than 5 minutes.

If the patient is beta blocked, you should use glucagon instead of adrenaline.

Tomorrow: Page 83 – Allergies in general and a bit of oncology