MRCP revision battle 48.1: Genital warts

Today's battles have a distinctly dermatological flavour to them...

MRCP revision battle 48.1: Genital warts
MRCP revision battle 48.2: Livedo reticularis and erythema ab igne
MRCP revision battle 48.3: Antiphospholipid syndrome
MRCP revision battle 48.4: Skin conditions associated with malignancy
MRCP revision battle 48.5: Sturge-Weber Syndrome
MRCP revision battle 48.6: Erythema multiforme
MRCP revision battle 48.7:  Toxic Epidermal Necrolysis and Steven-Johnson Syndrome



MRCP revision battle 48.1: Genital warts


Genital warts are not a topic I want to dwell on so lets make this very concise.


Posh medical name for genital warts = condylomata accuminata

Cause: HPV, most commonly strains HPV 6 and HPV 11.
Less than 1% of people who become infected with HPV develop warts.


Prevention: gardasil vaccine protects against HPV 6 and 11 (associated with warts) and 16 and 18 (associated with cervical cancer)


Treatment:

• 1st line: topical podophyllin/cryotherapy
• 2nd line: imiquimod

Lets move rapidly onwards...

MRCP revision battle 48.2: livedo reticularis and erythema ab igne

livedo reticularis is a mottled, reticulated vascular pattern that appears like 'purple lace' on the skin.

Click here for an image
Click here for another


Causes of livedo reticularis include:

• idiopathic - commonly occurs in young females
• secondary
• rheumatological: RA/SLE/PAN/dermatomyositis/antiphospholipid syndrome
• pancreatitis
• infections: TB/lyme disease/syphillis
• lymphoma

Note how similar it looks to erythema ab igne (AKA livedo recticularis e calore) which is a rash caused by prolonged heat exposure, for example by sitting by a radiator or holding a hot water bottle.  (photo form wiki commons, taken by Dr Heilman)

Now lets move on to look at one of the causes of livedo reticularis, antiphospholipid syndrome

MRCP revision battle 48.3: Antiphospholipid syndrome

Antiphospholipid syndrome is characterised by:

• recurrent venous/arterial thromboses
• fetal loss
• thrombocytopenia

Livedo reticularis may also be a feature.


Antiphospholipid syndrome is associated with:

• lupus anticoagulant - an inhibitor of the coagulation pathway in vitro; pro-coagulant in vivo
• anti cardiolipin antibodies - IgG and IgM

Management is with aspirin post thrombus, or if recurrent thromboses despite aspirin warfarin.

In pregnancy expert advice is needed; in general aspirin is taken once pregnant and LMWH started once the fetal heart is seen.  This is continued until 34 weeks.   This regime results in 70% success compared with 10% with nothing.


Now for some pictures...

MRCP revision battle 48.4: Skin conditions associated with malignancy

A brief run-through of a few skin conditions that can be associated with malignancy.

1.  Acanthosis nigricans

Acanthosis nigricans is a brown, velvety pigmentation of the skin, as illustrated below.




















Acanthosis nigricans is associated with:

• insulin resistance 
• diabetes
• acromegaly
• cushings
• obesity
• hypothyroidism
  
• PCOS
• adenocarcinoma - particularly of GI tract/stomach

2. Acanthosis palmaris

Acanthosis palmaris, also known as 'tripe palms' is associated with lung or GI cancer.




3. Erythema gyratum repens

Erthema gyratum repens can be just the most beautiful swirly patterned erythema - click here to see a picture.  Unfortunately it is associated with lung cancer.




4. Necrolytic migratory erythema

From a beautiful rash to a truelly ugly one - necrolytic migratory erythema is associated with glucagonomas.  Click here for more information and images.



5. Sweets syndrome

These are tender purple-red plaques associated with haematological malignancy and IBD.  The patient is likely to have a fever.  The picture below is from wiki commons, posted by Cohen:

On to a very brief battle, Sturge-Weber syndrome...

MRCP revision battle 48.5: Sturge-Weber Syndrome

Sturge-Weber syndrome is the association of a port wine stain on the face with ipsilateral vascular  malformations and epilepsy.




Glaucoma and learning difficulties may also be features.



Now for some target lesions...

MRCP revision battle 48.6: Erythema multiforme

Erythema multiforme is characterised by target lesions.

Two pictures of erythema multuforme are below; the second is by Dr Heilmann.

50% of cases of erythema multiforme are idiopathic.

Secondary causes include:

• drugs
• penicillin
• sulphonamides
• phenytoin
• carbamazepine
• ACE-i
• barbituates
• NSAIDs
• thiazides
• infections
• mycoplasma
• herpes
• orf

Management is to treat the underlying cause and supportive treatment.


For the final battle of the day on to what used to be considered as a severe form of erythema multiforme....

MRCP revision battle 48.7: Toxic Epidermal Necrolysis and Steven-Johnson Syndrome

Steven-Johnson Syndrome and Toxic Epidermal Necrolysis (TEN) are now consider to be varients of the same entity, with TEN being more severe.


They are characterised by irregular purpuric macules with occasional blistering and most patients also have extensive mucosal involvement. 

Although the appearence may initially seem similar to erythema multiforme (ableit more severe) histologically they are different:

• erythema multiforme - cell-rich infiltrate, lots of T lymphocytes
• SJS/TEN - cell-poor infiltrate, macrophages and dendrocytes

The difference between SJS and TEN is arbitrarily defined as SJS involves <10% body surface while TEN involves >30%.


The commonest cause of SJS/TEN is medication, with sulphonamides being the most commonly implicated drug.  

Other drug precipitants include:

• phenytoin
• carbamazepine
• barbituates
• allopurinol
• penicillin
• NSAIDs

The commonest time for SJS/TEN to develop is 9 to 14 days after starting a new drug.

Infections can also cause SJS/TEN.


In addition to the rash patients are systemically unwell and have a + Nikolsky's sign.


Management is:

• stop precipitating drug
• often ITU
• IV IG
• ?immunosupression ?plasmophoresis

MRCP revision battle 47.1: Membranous glomerulonephritis

A final assault on renal medicine!

MRCP revision battle 47.1: Membranous glomerulonephritis
MRCP revision battle 47.2: Diffuse proliferative glomerulonephritis
MRCP revision battle 47.3: Acute interstitial nephritis
MRCP revision battle 47.4: Chronic interstitial nephritis
MRCP revision battle 47.5: Alport's syndrome
MRCP revision battle 47.6: Renal papillary necrosis
MRCP revision battle 47.7: Mesangiocapillary glomerulonephritis



MRCP revision battle 47.1: Membranous glomerulonephritis


Membranous glomerulonephritis is the commonest cause of nephrotic syndrome in adults, accounting for around 30% of cases.

Peaks in incidence of membranous glomerulonephritis occur in the 2nd and 6th decade of life.


The key feature is IgG and C3 on the basemement membrane

The complication to be aware of is renal vein thrombosis which occurs in 5% of cases.


Secondary causes of membranous glomerulonephritis include:

• malignancy
• connective tissue disease: RA/SLE/sjogrens
• infection: HBV/HCV/malaria/syphilis
• drugs: NSAIDs/gold/penicillamine/captopril
• other: GBS/sarcoid

In terms of prognosis 1/3 recover spontaneously, 1/3 recover after treatment with immunosupression and 1/3 develop renal failure.



Now on to another glomerulonephritis...

MRCP revision battle 47.2: Diffuse proliferative glomerulonephritis

Diffuse proliferative glomerulonephritis classically presents after a streptococcal infection or impetigo.  It tends to affect children and young adults.


Diffuse proliferative glomerulonephritis tends to cause nephritic syndrome or acute renal failure.


Immunofluorescence shows C3 and IgG.
Serology shows decreased C3 and raised ASOT


Treatment is supportive and >95% recover.


Now lets consider nephritis...

MRCP revision battle 47.3: Acute Interstitial Nephritis

Interstitial nephritis is inflammation of the renal interstitium.



Acute interstitial nephritis

This is an immune reaction to drugs or infection.
It accounts for 2% of all acute renal failure but 25% of drug-induced renal failure.


Features include:

• acute renal failure
• hypertension
• systemic symptoms
• rash
• fever
• eosinophilia, raised IgE

>1% urinary eosinophils suggests diagnosis


Renal biopsy would show infiltration of the renal interstitium with:

• T lymphocytes
• macrophages
• plasma cells

Causes include:

• infections: hanta virus, leptospirosis, mycobacterium, staph, strep
• drugs: methicillin, NSAIDs, rifampacin, allopurinol, penicillin, cephalosporins, furosemide, thiazides, amphotericin, aspirin
• sarcoid

Lets move on to consider a hat-trick of causes of chronic interstitial nephritis

MRCP revision battle 47.4: Chronic interstitial nephritis

Chronic interstitial nephritis/tubulointerstitial nephritis can be caused by many conditions and results in fibrosis and tubular loss which manifests clinically as chronic renal failure




Analgesic nephropathy

Analgesic nephropathy is associated with long-term use of NSAIDs, and to a lesser degree paracetamol.


It may present as:

• sterile pyuria
• chronic renal failure
• renal pain (due to papillary necrosis)

An IVU will show 'cup and spill' calyces
Renal biopsy may show interstitial nephritis

Treatment is to stop the analgesics and managed any renal failure.


There is an increased risk of urothelial tumours.




Reflux Nephropathy

Reflux nephropathy is defined as small and irregularly scarred kidneys associated with vesico-ureteric reflux.

Almost always only occurs in first 5 yrs of life.

Associated with an increased risk of renal stones.



Balkan Nephropathy

Balkan nephropathy is a chronic interstitial renal disease found in a distribution along the River Danube.

It is associated with coppery yellow pigmentation of palms and soles.
There is raised beta 2 microglobinuria.

Urothelial malignancy is much increased - up to 200x risk.




Now on to Alport's syndrome...

MRCP revision battle 47.5: Alport's syndrome

Alport's syndrome is an inherited kidney disease with an incidence of 1 in 5000.

It is inherited in an X-linked dominant fashion 85% of the time; 15% are autosomal recessive.


Alport's is an abnormality in the gene that codes for type IV collagen.


It is associated with:

• abnormal GBM - 'basket weave' --> chronic renal failure, 30% nephrotic
• sensorineural deafness
• occular defects in 40%
• lenticonus = bulging lens capsule on slit lamp exam
• retinitis pigmentosa

Treatment is treating symptoms.

Onwards...

MRCP revision battle 47.6: Renal papillary necrosis

Renal papillary necrosis is a form of nephropathy involving the renal papilla (= location where medullary pyramids empty urine into minor calyx)


It can cause pain and a sterile pyuria.


An IVU may show 'cup and spill' calyces.


Causes of renal papillary necrosis may be recalled as 'POSTCARDS'

• pyelonephritis
• obstruction of renal tract
• shock
• TB
• cirrhosis of liver
• analgesic nephropathy
• renal transplant rejection
• diabetes
• sickle cell

On to the final battle of the day, mesangiocapillary glomerulonephritis...

MRCP revision battle 47.7: Mesangiocapillary glomerulonephritis

Mesangiocapillary glomerulonephritis, also known as membranoproliferative glomerulonephritis is a rare form of glomerulonephritis.


There are 3 subtypes:


Type 1:

• subendothelial immune deposits
• caused by cryoglobulinaemia, hepatitis C
• also associated with:
• hep B
• bacterial endocarditis
• SLE
• malaria
• sickle cell disease

Type 2:

• intramembranous electron-dense material --> 'double tramline'
• associated with partial lipodystrophy
• C3b nephritic factor present in 70%
• low C3

Type 3:

• associated with hepatitis B and C

Treatment is with steroids

50% of patients progress to end stage renal failure.

MRCP revision battle 46.1: Classification of bacteria

A completely random mixed bag today, bursting full of random nuggets of MRCP knowledge...


MRCP revision battle 46.1: Classification of bacteria
MRCP revision battle 46.2: Tumour supressor genes and Li Fraumeni Syndrome
MRCP revision battle 46.3: Mitochondrial disorders and Leber's Optic Atrophy
MRCP revision battle 46.4: Cytotoxic Agents
MRCP revision battle 46.5: Congenital infections
MRCP revision battle 46.6: Rheumatoid factor
MRCP revision battle 46.7: Lichen Planus





MRCP revision battle 45.1: Classification of bacteria


MRCP questions just love commenting on the colour/shape of bacteria.  Hopefully my simple picture below (which was also stuck next to the loo during finals!) might help you.  Note that gram positive bacteria have walls so stain purple/blue while gram negative bacteria don't and stain pink.

My way of remembering them is 'SES ('says') ABCD then L....MN then all the rest'


As well as their colour/shape their 'pattern' is useful to know too:

• pairs of cocci (= diplococci): neisseria gonorrhoea, neisseria meningitidis
• chains of cocci: streptococci, enterococci
• clumps of cocci: staphylococci

Now for some genetics...

MRCP revision battle 46.2: Tumour supressor genes and Li Fraumeni Syndrome

Tumour supressor genes code for proteins that provide a 'stop' signal to prevent cell division.  They therefore act as a barrier to the development of cancer.  As they are recessive genes both copies of the gene would have to be mutated to stop functioning.


The most famous tumour supressor gene is p53.

p53 is:

• found on chromosome 17
• the most commonly mutated gene in breast, colon and lung cancer
• a key regulator of apoptosis and prevents entry into the S phase of the cell cycle until the DNA is checked.

Li Fraumeni Syndrome is a rare condition in which there is an autosomal dominant p53 mutation.  More rarely it may be caused by a CHEK-2 mutation. Li Fraumeni syndrome is characterised by early onset of cancer, especially breast, sarcoma or soft tissue.  



Lets move on to mitochondrial disorders...

MRCP revision battle 46.3: Mitochondrial disorders and Leber's Optic Atrophy

mDNA mutates 10x more frequently than normal DNA.  However, there is a poor genotype to phenotype correlation so the mutations are often not noticed.


Since sperm do not contain mitochondria mitochondrial disorders are passed exclusively from mother to child.


The most famous mitochondrial disorders are:

1. Kearns Sayre - see battle 15.5
2. Leber's hereditary optic neuropathy.
3. Some forms of sensorineural deafness

Leber's hereditary optic neuropathy

• mDNA mutation
• progressive loss of central vision due to optic atrophy, begins in young adulthood
• if LHON 'plus' also:
• multiple-sclerosis type symptoms
• Wolff-Parkinson White

Next up - some cytotoxic agents (which sadly sounds more exciting than it is)

MRCP revision battle 46.4: Cytotoxic Agents

A quick run-through of the main mechanisms of action and MRCP-relevant side-effects of some common cytotoxic agents.


Vincristine

• Inhibits microtubule formation
• Used in:
• lyphoma
• leukaemia
• breast and lung cancer
• Side effects
• peripheral paraesthesia
• loss of tendon reflexes
• abdominal pain

Cisplatin

• Cross-links DNA
• Used in:
• testicular, cervical, bladder, lung, head and neck cancers
• Side effects
• nephrotoxic
• ototoxic
• peripheral neuropathy
• hypomagnesaemia
• myelosupression

Bleomycin

• Degrades DNA
• Used in:
• metastatic germ cell cancers
• non-Hodgkins lymphoma
• Side effects
• increased pigmentation
• pulmonary fibrosis

Doxorubicin

• inhibits RNA/DNA synthesis
• used in:
• leukaemia
• lyphoma
• breast cancer
• Side effects
• red colouration of urine
• SVT
• cardiomyopathy

Methotrexate

• inhibits dihydrofolate reductase
• used in:
• non-Hodkins lymphoma
• choriocarcinoma
• RA
• Side effects
• excreted by kidneys so should be avoided in renal disease
• should be avoided in significant ascites/pleural effusion as may accumulate then suddenly return to circulation causing myelosupression
• myelosupression
• mucositis
• pneumonitis

Cyclophosphamide

• alkylating --> cross links DNA. Inactive until metabolised by liver
• used in:
• CLL
• lymphoma
• sarcoma
• Side effects
• haemorrhagic cystitis 

To continue the randomness of the 46th set of battles lets look at congential infections

MRCP revision battle 46.5: Congenital infections

A few short notes on 5 infections mummies may have during pregnancy which can adversely affect the fetus...


Maternal rubella

• fetus is nearly always affected if rubella occurs during first 7 weeks of gestation
• fetus is nearly always OK if rubella occurs after 17 weeks of gestation
• Effects of rubella on fetus:
• sensorineural deafness
• congenital cateracts
• congenital heart disease
• glaucoma

Maternal toxoplasmosis

• fetus will only be affected if it is the first time the mother is exposed, unless she is immunosupressed
• classical triad is:
• cerebral calcification
• hydrocelphalus
• chorioretinitis

Maternal chickenpox

• if this occurs during the 1st trimester risk of limb deformity
• if mum has been in contact with chickenpox and is not sure if she is immune test for antibodies and if no natural immunity give immunoglobulin

Maternal CMV

• at least 75% of fetus' exposed to CMV are undamaged
• however, there is a risk of:
• intracranial calcification
• microcephaly
• cardiac/GI abnormalities

Maternal Parvovirus B19

• generally either fetal death or complete recovery

Now for a spot of rheumatoid factor

MRCP revision battle 46.6: Rheumatoid factor

Rheumatoid factor is an autoantibody against the Fc portion of IgG.  

Rheumatoid factor is found in 4% of the 'normal' population and 25% of elderly.


Rheumatoid factor is positive in low titres in chronic infections, for example:

• 10% syphyllis
• 20% pulmonary TB
• 50% leprosy

Rheumatoid factor is often positive in high titres in connective tissue disease, for example it is positive in:

• 70% of patients with RA
• virtually 100% of patients with RA with extra-articular manifestations
• >75% sjogrens
• 20-40% SLE
• 30% scleroderma

It may also be present in other immunological diseases, for example autoimmune liver disease or sarcoidosis.


Very high titres of rheumatoid factor may be found in cryoglobulinaemias


Rheumatoid factor is only useful in RA as an assessment of prognosis.  It is not useful for diagosis or or measuring level of activity.


Rheumatoid factor is detected by the Rose-Waaler test (sheep red cell agglutination) or the latex agglutination test.


Now to the final battle of the day - lichen planus

MRCP revision battle 46.7: Lichen Planus

Lichen planus is an intensely itchy rash characterised by purple papules with flat tops, often with white lines on the surface (=Wickham's striae).

The picture below (taken by Dr Tag-El -Din Anbar) illustrates lichen planus on an arm:

Mucus membranes may also be affected.


Management may be symptomatic, or with steroid creams.

Half of cases have resolved within 6 to 9 months and the majority of the rest will be gone within 18 months.



A lichenoid-like rash can also be caused by some medications, including:

• NSAIDS
• thiazide diuretics
• antimalarials
• betablockers
• gold injections
• mercury fillings

MRCP revision battle 45.1: Dialysis and complications

Back to my old nemesis renal medicine for another 7 battles...


MRCP revision battle 45.1: Dialysis and complications
MRCP revision battle 45.2: Anaemia in chronic renal failure
MRCP revision battle 45.3: Diuretics
MRCP revision battle 45.4: Proteinuria
MRCP revision battle 45.5: Renal osteodystrophy
MRCP revision battle 45.6: Radio-contrast nephropathy
MRCP revision battle 45.7: Minimal change disease




MRCP revision battle 45.1: Dialysis and complications


Lets start with a very matter-of-fact battle on dialysis and its complications


Brief overview of types of renal replacement therapy

1. Haemodialysis
• semi-permeable membrane
• solute transfer by diffusion
• excess fluid removed by creating a negative transmembrane pressure = ultrafiltration
2. Haemofiltration
• highly permeable membrane
• solute transfer by convection
• ultrafiltrate replaced by an equal volume of substitute fluid
• takes longer and is more expensive than haemodialysis but less haemodynamic instability so used for critically ill patients
3. Peritoneal dialysis
• dialysis fluid put into abdominal cavity via tenchkoff catheter
• solutes diffuse across peritoneal membrane
• ultrafiltration achieved by adding glucose to the dialysis fluid

Complications of dialysis

• Disequilibration syndrome
• occurs on initial dialysis
• manifests as nausea, vomiting, headache and altered consciousness
• caused by rapid changes in plasma osmolality
• Vascular disease
• Heart valve calcification - especially aortic valve
• Beta-2 microglobulin amyloidosis
• Arthritis
• Infections

Now to consider anaemia in renal failure...

MRCP revision battle 45.2: Anaemia in chronic renal failure

Anaemia is common in chronic renal failure and is usually due to:

• decreased production of erythropoetin
• iron deficiency

Treatment should be considered when Hb <11
The target for treatment should be Hb between 10.5 and 12.5


Correct any iron deficiency first; note that oral iron is often not enough and IV iron therapy may be needed.


If there is still anaemia the likely eryropoetin deficiency must be addressed.  Options are:

• Eryropoetin replacement with either epoetin (=recombinant human erythropoetin) or 
• darbepoetin (=hyperglycosylated derivative of epoetin with a longer half life)

Side effects of epoetin include:

• hypertension (25%)
• bone aches
• 'flu'
• rashes, urticaria
• pure red cell aplasia 
• low reticulocyte count
• anaemia
• antibodies
• increased risk of DVT as increased PCV

If no response to epoetin consider if the patient has an infection, inflammatory condition or aluminium toxicity, all of which can impair epoetin's effectiveness.


Note that blood transfusions are generally avoided in renal patients as they would make matching for transplants more difficult



Cross your legs as we move on to a battle of diuretics...

MRCP revision battle 45.3: Diuretics

Before I started my revision I thought I was very au-fait with diuretics - after all, I prescribe them daily.  However, a quick bond with the British National Formulary revealed some interesting gems.  So here's a quick recap of diuretics with a sprinkling of hopefully new information.



1. Loop diuretics

• work on the Na-K-2Cl transporter in the ascending loop of Henle
• examples include furosemide and bumetanide
• bumetanide is 40x more potent than furosemide for the same dose
• both work within 30 mins (if given IV) or 1 hr (if given orally) and their action is completed within 6 hours
• possible side effects include:
• hypokalaemia/natraemia
• retention if enlarged prostate
• tinnitus 
• pancreatitis

2. Thiazide diuretics

• work on the Na-Cl co-transporter in the DCT
• examples include bendroflumethiazide, indapamide and metolazone
• they work within 1 to 2 hours and have a duration of action of 12 to 24 hours
• possible side effects include:
• hypokalaemia/naturaemia
• hyperglycaemia
• pancreatitis

3. Aldosterone antagonists

• work by antagonising aldosterone 
• examples include spironolactone and eplerenone 
• possible side effects include:
• hyperkalaemia
• impotenence
• gynaecomastia

Now for the differentials of proteinuria...

MRCP revision battle 45.4: Proteinuria

Normal protein excretion in urine is <150mg/day


Causes of proteinura include:

• Renal causes
• UTI
• glomerulonephritis
• myeloma
• diabetes
• hypertension
• amyloid
• Extra-renal causes
• fever
• exercise
• psoriasis
• pregnancy

Orthostatic proteinuria is proteinuria which disappears when recumbant.   The cause of this is unknown but it is felt to be benign.


On to renal osteodystrophy...

MRCP revision battle 45.5: Renal osteodystrophy

Renal osteodystrophy refers to the bone pathology which results from the endocrine and electrolyte imbalances caused by chronic renal failure.


Derangements include:

• raised phosphate
• low calcium
• secondary hyperparathyroidism
• low vitamin D
• acidosis

The result on bones include:

• osteomalacia
• osteitis fibrosa cystica = hyperparathyroid bone disease
• osteoporosis
• osteosclerosis 'rugger jersey' spine

Management is:

• calcichew - to bind phosphate in the gut
• vit D analogues - eg adcal D3/calceos/calcichew = colecalciferol

On to the slightly more stimulating contrast nephropathy...

MRCP revision battle 45.6: Radio-contrast nephropathy

Radiocontrast nephropathy complicates up to 10% of procedures involving contrast.

Contrast nephropathy presents as non-oliguric acute renal failure 1 to 5 days post procedure.


Risk of contrast nephropathy can be reduced by:

• good hydration/normal saline
• oral n.acetyl cysteine

Risk of contrast nephropathy is increased by:

• increased amount of contrast
• hypovolaemia
• myeloma
• increasing age
• diabetes
• raised calcium
• chronic renal failure

Remember that metformin must be withheld before and for 48 hrs post IV contrast due to risk of lactic acidosis. 




Now to end on a high with a battle with minimal change disease...

MRCP revision battle 45.7: Minimal change glomerulonephritis

Minimal change glomerulonephritis almost always presents as nephrotic syndrome

It is responsible for 80% of cases of nephrotic syndrome in children and around a quarter of cases in adults.


Its name 'minimal change' comes from the fact that under a light microscope the kidney looks normal; if an electron microscope is used you can see podocyte fusion.


Minimal change glomerulonephritis causes a highly selective proteinuria with only smaller proteins leaked.


Most causes are idiopathic but 10-20% are associated with:

• NSAIDs/gold/rifampacin
• hodgkins, thyroma
• mononucleosis

It is believed to be T-lymphocyte mediated.


Treatment is with corticosteroids - 80% of cases respond
Cyclophosphamide can be used in non-responders.


The prognosis for minimal change glomerulonephritis is (fairly) good:

• 1/3 recover completely
• 1/3 suffer infrequent relapses
• 1/3 suffer frequent relapses
• BUT - <1% proceed to end-stage renal failure

Tomorrow's battles will be a completely random bag, then a final renal push (the end of the hattrick) will occur the day after.

MRCP revision battle 44.1: Antipsychotic medication

Today is a psychiatry and overdose fest...


MRCP revision battle 44.1: Antipsychotic medication
MRCP revision battle 44.2: SSRIs
MRCP revision battle 44.3: Serotonin syndrome
MRCP revision battle 44.4: Baby blues, post natal depression and psychosis
MRCP revision battle 44.5: Quinine toxicity/overdose
MRCP revision battle 44.6: Theophylline overdose
MRCP revision battle 44.7: Ethylene glycol poisoning



MRCP revision battle 44.1: Antipsychotic medication

Antipsychotic medications are used in the treatment of schizophrenia, severe anxiety, mania and occasionally for their sedative properties.

Antipsychotic medications have an immediate sedative action but their antipsychotic action may tak up to 3 weeks to become effective.


Atypical antipsychotics

Atypical antipsychotics are the newer drugs.  They produce a highly selective blockade of the mesolimbic D2 receptors and serotonin 5HT2A receptors.

Examples include amisulperide, olanzapine, quetiapine, risperidone and clozapine.


Side effects include:

• weight gain
• nausea, dyspesoa
• hyperglucaemia and impaired glucose tolerance
• increased risk DVT
• increased risk stroke (especially olanzapine and risperidone)
• clozapine only:
• 1% agranulocytosis/neutropenia - therefore weekly blood tests for 1st 6 months then fortnightly afterwards
• 3% seizures

All antipsychotics have roughly the same effectiveness except clozapine, which is better.  However, in light of its worse side effect profile clozapine is only recommended if 2 others have already failed.


Typical antipsychotics

Typical antipsychotics are the older drugs,
Examples include haloperidol, chorpromazine, phenothiazine and sulperide.


Side effects of the typical antipsychotics include:

• extrapyramidal side effects
• anticholingergic effects
• antihistaminergic effects
• photosensitivity (especially phenothiazine)
• prolonged QT
• lower seizure threshold
• hyperprolactinaemia.

Now on to SSRIs...

MRCP revision battle 44.2: SSRIs

Selective Serotonin Reuptake Inhibitors (SSRIs) do exactly what their name implies: selectively inhibit serotonin reuptake.

Examples include citalopram, escitalopram, fluoxetine, paroxetine and sertraline.


They are widely used for depression, anxiety, post-traumatic stress disorder and panic disorder.
Fluoxetine, paroxetine and sertraline can be used in OCD.


There are many side effects, the commonest of which is GI disturbance.

Other possible side effects to be aware of include:

• interaction with platelet function --> increase risk of GI bleed
• hyponatraemia
• urinary retention

Given the increased risk of bleeding SSRIs should be avoided if on heparin/warfarin - use mirtazepine instead.

The safest SSRI post MI is sertraline.



If combined with MAOIs/moclobemide there is a serious risk of toxicity and serotonin syndrome - do not start MAOIs until 5 weeks after stopping fluoxetine, 2 weeks after stopping sertraline or 1 week after stopping any other SSRI.  Conversely you must wait 2 weeks after stopping MAOIs before starting an SSRI.


Triptans and SSRIs must also not be combined due to increased risk of serotonin syndrome.


When SSRIs are stopped they should be reduced over 4 weeks to decrease withdraw.  Paroxetine is worst on stopping.


Now on to the next battle to explore serotonin syndrome....

MRCP revision battle 44.3: Serotonin syndrome

Serotonin syndrome is characterised by the triad of:

• autonomic hyperactivity
• hypertension
• hyperthermia
• tachycardia
• mydriasis
• neuromuscular abnormality
• hyperreflexia
• clonus
• tremor
• hypertonicity
• mental state changes

Drugs associated with serotonin syndrome include:

• lithium
• carbamazepine
• triptans
• illegal drugs
• LSD
• cocaine
• MDMA
• antidepressants
• MAOIs
• SSRIs
• St Johns Wort

Treatment:

• remove cause
• supportive treatment
• cyproheptadine - a 5HT antagonist
• chlorpromazine for hyperthermia and agitation

 Now for some postnatal depression...

MRCP revision battle 44.4: Baby blues, post natal depression and psychosis

Every now and then the MRCP exam will throw a slightly curve-ball question about a woman who has recently given birth being depressed.  The key facts to know ready to deal with this are:

1. 'baby blues'
• affects 60-70% of mothers 
• tends to last for 3 to 7 days
• characterised by being weepy and irritable
2. post natal depression
• affects 10% of mothers
• begins 1 to 3 months after childbirth
3. postpartum psychosis
• affects 0.2% of mothers
• riskiest period is 2 to 3 weeks post partum
• there is a 20% risk of reccurence with subsequent births

 Next - on to an overdose

MRCP revision battle 44.5: Quinine toxicity/overdose

Quinine is used in the prevention of falciparum malaria and the treatment of nocturnal leg cramps.

It is very toxic in overdose and can be toxic in some individuals at therapeutic doses.
Quinidine, a stereoisomer of quinine and a class Ia antiarrythmic, can be toxic in a single dose.


Signs/symptoms include:

• tinnitus
• hearing loss
• abdominal pain
• blurred vision
• hypotension (due to alpha blockade)
• long QT

There is a risk of irreversible blindness.


Treatment is recurrent doses of activated charcoal and supportive management


Now for another overdose requiring activated charcoal...

MRCP revision battle 44.6: Theophylline overdose

Theophylline/aminophylline has a narrow therapeutic window so overdoses may occur accidentally.


Signs and symptoms of toxicity include:

• vomiting
• tachycardia
• arrythmias
• seizures
• confusion

Treatment is with repeated doses of activated charcoal.  Haemoperfusion and haemodialysis may also be considered.



And to finish off the day, and the hattrick of overdoses - an antifreeze overdose

MRCP revision battle 44.7: Ethylene glycol poisoning

Ethylene glycol = antifreeze.


The stages of ethylene glycol poisoning are:

1. alcohol drunk-like state
2. metabolic acidosis with high anion gap
3. acute renal failure

Treatment is fomepizole, an inhibitor of alcohol dehydrogenase.
The old-fashioned treatment failing this is to give lots of ethanol which competes with the ethylene glycol for liver metabolism and prevents glyclic acid being produced.

Haemodialysis is a final option.

MRCP revision battle 43.1: Post renal-transplant complications

I'll admit it: I've been avoiding renal revision.  It's complicated I never understand it and it leaves me internally angry.  However dear friends I'm afraid the time has come to face a fully renal day.  On the menu is...


MRCP revision battle 43.1: Post renal-transplant complications
MRCP revision battle 43.2: Polycystic kidney disease and renal cysts
MRCP revision battle 43.3: Renal tubular acidosis
MRCP revision battle 43.4: Haematuria
MRCP revision battle 43.5: Renal calculi
MRCP revision battle 43.6: Focal Segmental Glomerulonephritis
MRCP revision battle 43.7: Acute renal failure




MRCP revision battle 43.1: Post renal-transplant complications

A kidney transplant can give a renal patient their life back as it frees them from endless dialysis sessions.  However, with kidney transplants come the risk of rejection/failure, complications and the burden of immunosupression...


Rejection


Acute rejection (less than 6 months post graft) presents as rising creatinine, possibly with fever and graft pain.  Biopsy would show immune cell infiltration.  Treatment is with high dose IV methylprednislone


Chronic rejection (greater than 6 months post graft) presents as gradually rising creatinine and proteinuria.  Biopsy would show fibrosis.  There is no effective treatment.


Overall graft survial is around 90% at 1 yr, 70% at 5 yrs and 50% at 10 yrs.




Non-renal complications

• Non-Hogkins Lymphoma - 20-50x increased risk due to ciclosporin use
• Skin cancer - 5-20x increased risk due to azothioprine
• Widespread warts/fungi/herpes zoster due to T cell supression by immunosupressives
  
• Cardiovascular disease - 10-20x increased risk
• CMV - give oral ganciclovir
• Pneumocystis carini pneumonia - give cotrimoxazole prophylaxis for first 6 months post transplant
• if previous TB give isoniazid for first year
• gout
• Diabetes - develops in 3-5%, ?due to tacrolimus

The common immunosupressants

• Ciclosporin
• inhibits T cell phosphatase calcineurin
• can cause tremor, hypertension, gum hypertrophy
• Tacrolimus
• decreases T cell activation
• ?risk of diabeets
• Azothioprine
• contraindicated with allopurinol as risk of life-threatening bone marrow supression
• is an anti-proliferation drug 
• TPMT test can be used to look for patients prone to toxicity
• side effects include bone marrow supression and pancreatitis.
• Mycophenolate
• anti-proliferative
• causes diarrhoea
• Sirolimus
• blocks IL2 so inhibits T cell division
• can provoke hyperlipidaemia
  

Now lets move on to polycystic kidney disease....

MRCP revision battle 43.2: Polycystic kidney disease and renal cysts

The classical cause of renal cysts is polycystic kidney disease.


Polycystic kidney disease affects around 1:1000.  


Type 1 is inherited on chromosome 16
Type 2 is inherited on chromosome 4


The US criteria for diagnosing polycystic kidney disease in a patient with a positive family history is:

• 2 cysts if aged less than 30
• 2 cysts in both kidneys if aged 30-59
• 4 cysts in both kidneys if aged greater than 60

Signs/symptoms of polycystic kidney disease include:

• renal enlargement
• abdominal pain
• hypertension
• renal failure

Associated features include:

• liver cysts
• subarachnoid haemorrhage
• mitral valve prolapse

Other causes of renal cysts include:

• autosomal recessive polycystic kidney disease
• chromosome 6
• tend to develop end stage renal failure in childhood
• fibrosis of liver
• Von-Hippel-Lindau (see battle 15.2)
• autosomal dominant on chromosome 3
• pre-maligant
• tuberous sclerosis
• auto dom on chromosome 9 or 16
• simple cysts
• occur in less than 2% of under 50s but up to 20% of over 70s.

Now for some renal tubular acidosis...

MRCP revision battle 43.3: Renal tubular acidosis

Renal tubular acidosis is a condition caused by the kidneys failing to correctly acidify the urine.

All types of renal tubular acidosis are associated with:

• hyperchloraemic metabolic acidosis
• normal anion gap

The three main types of renal tubular acidosis are:


Type 1 renal tubular acidosis: Distal

This is due to the kidney not excreting hydrogen ions in the distal tubule

Causes:

• idiopathic
• SLE/RA
• hypercalcaemia
• drugs: lithium, amphotericin

Complications:

• ricketts
• growth failure
• nephrocalcinosis
• renal calculi - calcium phosphate stones
• low potassium

Diagnosis is by oral acid load with ammonium chloride - the urine should acidify, but in type 1 renal tubular acidosis urine pH will remain >5.5

Treatment is with oral bicarbonate



Type 2 renal tubular acidosis: proximal

This is  due to the kidneys failing to reabsorb bicarbonate in the proximal tubule

Causes include:

• Wilson's syndrome
• Fanconi syndrome
• cystinosis
• myeloma
• interstitial nephritis
• drugs - lead, acetazolamide, old tetracycline

Complications include:

• osteomalacia
• low potassium

Diagnosis is by IV bicarbonate loading , which will result in a high fractional excretion of bicarb.

Treatment is with oral bicarbonate.


Type 4 renal tubular acidosis

This is caused by hypoaldosteronism, resulting in hyperkalaemia.

Treatment is to treat cause and control hyperkalaemia



The astute amongst you may have noted the lack of a type 3 - this is because those clever renal physicians decided that, upon reflection, what they had named type 3 was probably just a combination of types 1 and 2.


If you had to boil the above battle down to a set of key facts, I'd go with:

• all cause hyperchloraemic metabolic acidosis with a normal anion gap
• types 1 and 2 both cause hypokalaemia and are both treated with oral bicarb
• type 3 causes a hyperkalaemia and is treated by treating the cause

Now on to a symptom-based battle...

MRCP revision battle 43.4: Haematuria

When considering haematuria you need to subdivide into microscopic and macroscopic.


Causes of transient, non-visible/microscopic haematuria include:

• UTI/pyelonephritis
• menstrual period
• vigorous exercise
• sex

Causes of persistent, non-visible/microscopic haematuria include:

• renal stones
• prostatitis
• urethritis
• stones
• cancer
• benign prostatic hypertrophy
• IgA nephropathy
• benign familial haematuria

Macroscopic haematuria can be caused by:

• infection: UTI
• renal disease: renal papillary necrosis, IgA nephropathy, glomerulonephritis
• malignancy- although note just 4% of cases of bladder cancer will be asymptomatic except for haematuria
• renal stones
• prostatic hypertrophy

NICE guidelines demand urgent referral for:

• patients of any age with painless macroscopic haematuria
• patients aged 40+ with recurrent/persistent UTI and haematuria
• patients aged 50+ with unexplained microhaematuria

And as always consider whether the result could be spurious;  false positive blood on dipstick can occur with:

• beetroot
• porphyria
• alkaptonuria
• rifampicin

Just a brief note at the end of this battle on benign familial haematuria.  This accounts for around 25% of patients referred to nephrologists with microscopic haematuria.  It is associated with the basement membrane being thinner than normal (<250nm compared with normal 450nm).   Patients generally have a normal BP and normal renal function.  They are however followed up as there is a small risk of renal failure.


Now on to a battle I fight daily in my current job... renal stones...

MRCP revision battle 43.5: Renal calculi

"Good god" exclaimed my medical student "that man looks like he's in labour!"  Indeed, glancing into cubicle 4 there was a man who resembled a woman trying to give birth - he was puffing away at the entonox the ambulance crew had given him, pacing as if he just couldn't get comfortable and every now and then was hit by a pain that caused him to yelp out.  "I think he's got renal stones" I said.  The medical student looked hugely impressed at my confident diagnosis from a distance; I'm sure however you aren't and the MRCP examiners wouldn't be either, giving a classical description of renal colic just to lull you into a false sense of security before asking you a random question on the minuitae, so lets dive into the small print...


Location of stone

Classical renal colic ("loin to groin pain") suggests the stone is in the ureter
Stones in the bladder/urethra may cause pain on passing water


Type of stone

Commonest stone = calcium oxalate = 75%

• Calcium oxalate stones are spikey and radioopaque
•  Foods associated with increased levels of oxalate include chocolate, tea, rhubarb and spinach
• However, medical conditions which result in excessive colonic absorption of oxalate are more likely to predispose, for example:
• Crohns disease
• post ileal resection
• chronic pancreatitis
• short bowel syndrome
•  Hypercalciuria/hypercalcaemia also predispose to calcium oxalate stones:
• hyperparathyroidism
• sarcoidosis
• hyperthyroidism
• vit D excess
• drugs: lithium, loop diuretics
• Prevention of calcium oxalate stones includes drinking more water and possibly thiazide diuretics  or pyridoxine

Next commonest stone = magnesium ammonium phosphate (=struvite, =triple phosphate) =10-20%

• radiologically tend to be 'large' with a 'staghorn' appearence.  Radioopaque
• tend to form in alkaline urine so UTIs with ureaplasma urealyticum or proteus predispose

Other radioopaque stones include calcium phosphate.


Cysteine stones (1% total) are semi-radio opaque and form when renal tubular defects are present.



Uric acid stones (5-10%) are radiolucent.  They form when there is excess uric acid.  Prevention includes allopurinol and urinary alkalinisation.


The other radiolucent stone is xanthine, but this accounts for <1% of all stones.



Blood on urine dipstick is often seen as a prerequisite for renal stones, however the reality is that 50% of those with loin to groin pain and a positive blood on dipstick won't have renal stones while 20% of those with loin to groin pain and real renal colic won't have any blood on their dipstick....



Lets now move on to continue our slow battle through the various forms of glomerulonephritis...

MRCP revision battle 43.6: Focal Segmental Glomerulonephritis

Focal segmental glomerulonephritis accounts for less than 10% of nephrotic syndrome in children but up to 20% in young adults.



The characteristic feature of focal segmental glomerulonephritis is IgM and C3 deposits in affected areas.



Focal segmental glomerulonephritis may be primary or secondary to:

• reflux
• IgA glomerulonephropathy
• Alport's syndrome
• heroin abuse
• vasculitis

First line treatment is corticosteroids, which produce a response in around 30%.

25% of cases will progress to end stage renal failure, and if these are treated by renal transplant there is a 20-50% recurrence rate.

2% of patients suffer a rapid detioration


On that apt note lets move on to acute renal failure...

MRCP revision battle 43.7: Acute renal failure

Acute renal failure is one of those topics which is barely mentioned at medical school then suddenly becomes almost central to your day-to-day life as a medical houseofficer.  It also then pops up not infrequently in MRCP questions....




Acute renal failure is defined as a significant detioration in renal function occuring over hours to days.  

It is usually oliguric (<500mls/24 hrs)
However, it is non-oliguric in 10% of cases, including:

• gentamycin/amphotericin toxicity
• radio-contrast nephropathy
• interstitial nephritis

When approaching renal failure everyone repeats the mantra 'is it pre-renal, renal or post-renal'.  A recap of a few of the causes follows:





Pre-renal causes:

• sepsis
• hypovolaemia
• cardiac failure
• liver failure
• NSAIDS/ACE-i (interfere with renal blood flow)

Renal causes (generally acute tubular necrosis):

• nephrotoxic drugs
  
• gentamycin
• amphotericin
• tetracyclines
• contrast agents
• myeloma
• myoglobin (rhabdomyolysis)
• vasculitis
• glomerulonephritis

Post renal:

• any urinary tract obstruction

Important points to enable one to distinguish ATN from pre-renal uraemia are shown in the table below:

Essentially in pre-renal failure the kidneys are still working so are trying to concentrate the urine, whereas in ATN they aren't.



Going through the management of acute renal failure is a bit beyond the scope of this battle (and if you're taking MRCP you are probably already very familiar with it) so I'll finish by just briefly recapping indications for dialysis:

• refractory pulmonary oedema
• persistent hyperkalaemia (>7mmol/l)
• severe metabolic acidosis (pH<7.2 or BE <10)
• uraemic encephalopathy
• uraemic pericarditis
  

Thats all the battles for today.  Tomorrow we're back for a mixed bag before embarking on another renal day....

MRCP revision battle 42.1: Bell's Palsy

Yet another assault on the neurology knowledge-mountain with 7 neurology-focused battles...

MRCP revision battle 42.1: Bell's palsy
MRCP revision battle 42.2: Mononeuropathies
MRCP revision battle 42.3: Carpal tunnel syndrome
MRCP revision battle 42.4: Diabetic neuropathy
MRCP revision battle 42.5: Nystagmus
MRCP revision battle 42.6: Miosis
MRCP revision battle 42.7: Picks Disease



MRCP revision battle 42.1: Bell's palsy



Bell's palsy is an acute, unilateral, idiopathic facial nerve paralysis.

It affects LMN.


Classical features are:

• sudden onset unilateral facial weakness
• numbness/pain behind ipsilateral ear
• absent taste from anterior 2/3rds of tongue
• dry eyes
• hypersensitivity to sound

Treatment is prednisolone for 10 days.
Some evidence suggests giving aciclovir as varicella zoster antibodies are often raised.
The eye should be protected - artificial tears, taping of eye at night, ?tarsorrhaphy.


Most cases fully recover; 15% will have a prolonged or incomplete recovery.
Some subsquently suffer from 'crocodile tears' = eating stimulates unilateral lacrimination instead of salivation.


Now on to some more mononeuropathies...

MRCP revision battle 42.2: Mononeuropathies

Mononeuropathies are lesions of individual nerves.  The main causes of mononeuropathies are trauma or entrapment.


If 2 or more nerves are affected it is called mononeuritis multiplex. Causes may be remembered by the mnemonic DRAWS PLC:

• diabetes
• rheumatoid
• amyloid
• wegeners
• sarcoid/SLE
• PAN
• leprosy/lyme disease
• carcinomatosis/churg strauss

Important individual mononeuropathies to be familiar with include:


Key nerves of the arm: RUM - radial nerve C5-T1, ulnar never C6-T1 and median nerve C7-T1


Radial Nerve

• Origin: C5-T1
• Route: radial groove in humerus then anterior to the lateral epicondyle
• Sensory supply: lateral 3.5 fingers in back of hand; only small area at base of thumb unique
• Motor supply: tricipes and extensors of wrist/fingers plus suppinators
• Classical presentation: 'Saturday night paralysis' - fall asleep with arm across back of chair, compress radial nerve in its groove and bruise it so awake with wrist drop.

Ulnar Nerve

• Origin: C6-T1
• Route: posteriomedial aspect of humerus then adjacent to ulna.  Runs superficial to flexor retinaculum into hand.
• Sensory supply: medial 1.5 fingers
• Motor supply: interossei, hypothenar eminence, medial 2 lumbicals
• Classical presentation: claw hand/unable to cross fingers 

Median Nerve

• Origin: C7-T1
• Route: medially, goes through carpal tunnel
• Sensory supply: lateral 3.5 fingers palmar aspect of hand plus nail beds of these fingers
• Motor supply: pronator, LOAF = 1st and 2nd lumbricals, opponens pollicis, abductor pollicis brevis, flexor pollicis brevis (=thenar enimence)
• Classical presentation: carpal tunnel syndrome 

Carpal Tunnel Syndrome is so common it deserves its very own battle...

MRCP revision battle 42.3: Carpal tunnel syndrome

Carpal tunnel syndrome is a mononeuropathy of the median nerve at the carpal tunnel = space under the transverse carpal ligament and above the carpal bones.


It is the commonest mononeuropathy.


Classical presentation is pain in hand and arm with paraesthesia in thumb, index and middle fingers.  The pain is often worse at night and is relieved by dangling the hand out of bed and shaking it.


'Bedside tests' include:

• Phalen's test = maximal wrist flexion ('praying') for 1 minute recreates symptoms
• Tinel's test = tapping over nerve at wrist recreates symptoms

(I remember which way round these tests go by thinking 't for tapping, t for tinel)


Associations with carpal tunnel syndrome include:

• diabetes
• acromegaly
• hypothyroidism
• pregnancy
• RA

 Management may be conservative, spliting, steroid injections or surgery.


Now on to some diabetic neuropathy...

MRCP revision battle 42.4: Diabetic neuropathy

Diabetics may suffer from several different types of neuropathy.



1. Diabetic sensory neuropathy

The classic diabetic neuropathy is sensory neuropathy.  This causes a distal numbness ('glove and stocking') with tingling and pain.  

Treatment:

• 1st line: TCA
• 2nd line: gabapentin, pregabalin

2. Diabetic amyotrophy

Diabetic amyotrophy is sometimes known as proximal diabetic neuropathy.  This causes painful wasting of the quadriceps.   It is thought to be caused by occlusion of the vasa nervorum of the proximal lumbar plexus.  There is loss of the knee reflexes.




3. Autonomic neuropathy

If you need a recap refer back to revision battle 32.7



4. Mononeuritis multiplex

Particularly of CN III and VI.



Next up... a bit of nystagmus...

MRCP revision battle 42.5: Nystagmus

Nystagmus is involuntary, jerky eye movements.  

Nystagmus at the extremes of gaze is normal.


Horizontal nystagmus may be due to:

• vestibular lesions - acutely the nystagmus is away from the affected side
• cerebellar lesions - tends to be fast nystagmus and towards the affected side
• MS - suspect if nystagmus is more in the eye which is abducting
• benign positional vertigo - suspect if nystagmus varies with head position
• peripheral lesion - suspect if also tinnitus/other signs

Down beat nystagmus is associated with:

• Arnold Chiari malformations
• Syringobulbia  (not sure what these are? revise battle 11.3!)

Upbeat nystagmus is associated with:

• cerebellar vermis lesions
• organophosphate poisoning

Sticking with eyes we're now going to consider miosis....

MRCP revision battle 42.6: Miosis

Miosis is a small pupil.

Causes of miosis include:

(my personal mnemonic for miosis: AAA pooch)

• age
• Argyll Robertson pupil
• antipsychotics
• pontine haemorrhage
• pilocarpine
• opiods
• organophosphates
• cluster headache
• Horners

On to Pick's disease....

MRCP revision battle 42.7: Picks Disease

Pick's disease is the eponym for frontotemporal dementia.


It presents as loss of inhibition, socially unacceptable behavior, loss of empathy and compulsive behaviour.  There may also be loss of language skills.


Memory and spatial skills remain intact.


Pathophysiologically there are tau-positive inclusions.

 
There is no cure.

MRCP revision battle 41.1: Horner's syndrome

Today is another day of completely random battles... with a mnemonic of a addicts hammock and some fevers of unknown cause hopefully each battle should have something of interest in it...


MRCP revision battle 41.1: Horner's syndrome
MRCP revision battle 41.2: Gynaecomastia
MRCP revision battle 41.3: Gingival Hyperplasia
MRCP revision battle 41.4: Leptospirosis
MRCP revision battle 41.5: Opioid and benzo conversions
MRCP revision battle 41.6: Pyrexia of unknown origin
MRCP revision battle 41.7: Fitness to fly



MRCP revision battle 41.1: Horner's syndrome

Horner's syndrome is the triad of:

• miosis
• ptosis
• anhydrosis

 It is caused by an interruption of the sympathetic pupillomotor fibres



Causes may be:

• central - which causes anhydrosis of the face, arm and trunk
• pre-ganglionic = second order - which causes anhydrosis of face
• post-ganglionic = third order - which causes no anhydrosis

A general way to remember the causes is PC Stem:

• pancoast tumour
• cervical rib
• cluster headache
• carotid artery dissection
• stroke
• syringomyelia
• trauma
• thyroidectomy
• encephalitis
• multiple sclerosis

 An alternative way to try and learn them by their location is:

• central: STEMS 
• stroke
• tumour
• encephalitis
• multiple sclerosis
• syringomyelia
• pre-ganglionic: PCT
• pancoast tumour
• cervical rib
• trauma
• thyroidectomy
• post ganglionic: 2Cs
• carotid artery dissection
• cluster headache

Now for some big breasts...

MRCP revision battle 41.2: Gynaecomastia

Gynaecomastia = enlargement of male breast tissue.


Causes can be divided into:


Physiological

• adolescence
• increasing age - due to low testosterone

Drugs (a mnemonic to remember drugs causing gynaecomastia is a addicts hammock)

• antipsychotics
• ACE inhibitors
• digioxin
• diazepam
• isoniazid
• cimetidine
• TCA
• spironolactone
• heroin
• amiodarone
• metronidazole
• marijuana
• omeprazole
• calcium channel blockers
• ketoconazole

Pathological

• klinefelters
• liver cirrhosis
• hyperthyroidism

So from enlarged breasts to enlarged gums...

MRCP revision battle 41.3: Gingival Hyperplasia

Gingival hyperplasia is the overgrowth of the ginival (=gum) tissue.


Photos of gingival hyperplasia have appeared in part 2 written exams so a grasp of the main differentials is worthwhile.


Conditions to consider include:

• poor oral hygiene leading to gingivitis
• AML
• vitamin C deficiency
• pregnancy
• drug-induced casues:
• phenytoin
• ciclosporin
• calcium channel blockers (nifedipine, verapamil)

Now for a change to a spirochaete...

MRCP revision battle 41.4: Leptospirosis

Leptospirosis, also known as Weil's disease, is a disease caused by infection with the spirochaete leptospira interrogans.


It is classically caught from water contaminated with rat's urine, so suspect it as a diagnosis in those in questions who have recently fallen into rivers/out of rowing boats.


After a 2 to 20 day incubation period the patient develops:

• fever
• myalgia
• cough/haemoptysis
• headache

The patient then either makes a good recovery or develops:

• meningitis
• jaundice
• renal failure (50%)

Treatment is with penicillin/amoxicillin/doxycycline.



Lets move on to some conversions...

MRCP revision battle 41.5: Opioid and benzo conversions

Occasionally in real-life/MRCP exam you may need to convert between different drugs in the same family, so this revision battle briefly covers 2 popular families: the opioids and the benzos.



Opioids

First, as an aside: remember opiate refers to a substance derived from opium (from the poppy) while opioids are synthetic/semi-synthetic versions of opiates.

• PO codeine to PO morphine: divide by ten
• PO tramadol to PO morphine: divide by five
• PO morphine to PO oxycodone: divide by two
• PO morphine to S/C morphine: divide by two
• PO morphine to S/C diamorphine: divide by three
• PO morphine to S/C oxycodone: divide by three
• morphine to fentyl: divide by 100

Other misc notes:

• codeine relies on conversion to an active form by the P450 enzyme group.  Not all patients are able to do this (roughly 10% of the population struggle), and other drugs (such as SSRIs) may interfere with the effectiveness of conversion so the same amount of codeine may have a very variable analgesic effect on different people.
• doses of all opioids should be reduced in renal failure except fentanyl
• if asked to prescribe a breakthrough dose this is usually 1/6th of the total 24hr dose.

Benzos (and derivative)


Rough conversions are:

Chlordiazepoxide 15mg = Temazepam 10mg = Diazepam 5mg = Lorazepam 0.5mg


Decrease by 1/8th every 2 weeks.



Now for a little pyrexia of unknown origin...

MRCP revision battle 41.6: Pyrexia of unknown origin

Petersdorf and Beeson defined pyrexia of unknown origin (PUO) as:

• fever >38.3C on several occasions
• longer than 3 weeks
• with no diagnosis reached after 1 week of inpatient investigation

Causes:

• infections:
• abscesses
• TB
• malaria
• any other varient...
•  malignancy
• lymphoma
• hypernephroma
• leukaemia
• atrial myxoma
• connective tissue disease
• RA
• SLE

Daily spikes: abscess; TB; schistosomiasis
Twice daily spikes: leishmaniasis


On to the final battle of the day - fitness to fly...

MRCP revision battle 41.7: Fitness to fly

When a patient can fly pops up intermittently, particularly in part 1 written.  The following periods after various medical events at which it is considered safe to fly are quoted from the excellent patient.co.uk website and references can be found there.

• uncomplicated MI: 7 days
• complicated MI: 4 weeks
• CABG: 10 days
• PCI: 5 days

• pneumothorax: 2 weeks post resolved CXR

• pregnancy: contraindicated after 36 weeks gestation in singleton pregnancy or 32 weeks gestation if multiple pregnancy

• laparoscopy/colonoscopy: 24 hrs
• abdominal surgery: 10 days

• cast: 24 to 48 hrs

• CVA: 10 days

• sickle cell: needs in flight oxygen

MRCP revision battle 40.1: Oxygen dissociation curve

After a few days of 'pure' topics its back to the joys of a mixed bag for battle set 40.  Be prepared for a rapid tour through everything from poisoning to mountain sickness and pharmacology!


MRCP revision battle 40.1: Oxygen dissociation curve
MRCP revision battle 40.2: Carbon monoxide poisoning
MRCP revision battle 40.3: Acetylator status
MRCP revision battle 40.4: Generalised lymphadenopathy
MRCP revision battle 40.5: Acute mountain sickness
MRCP revision battle 40.6: Trisomies - Down's, Edward's and Patau's
MRCP revision battle 40.7: Hereditary angioedema




MRCP revision battle 40.1: Oxygen dissociation curve


The oxygen dissociation curve illustrates now easily haemoglobin gives up oxygen at a certain partial pressure of oxygen.

A shift in the curve to the left means lower oxygen delivery (L for left L for lower delivery).  This means the haemoglobin has a higher affinity for the oxygen.

Causes of a shift to the left include:

• less acidity
• lower temperature
• less 2,3 DPG
• HbF
• carboxy/methyl haemoglobin

A shift in the curve to the right means higher oxygen delivery, and hence the haemoglobin has a lower affinity for the oxygen.

Causes of a shift to the right include:

• higher acidity
• higher temperature
• higher levels of 2,3 DPG

The Bohr effect states that the curve will move to the right when there is a higher concentration of CO2 (and hence higher acidity).  This explains how the body releases oxygen to the tissues that need it the most.


The Haldane effect states that in the presence of raised oxygen carbon dioxide will bind less well to haemoglobin.




After that chunk of physiology lets go for a bit of poisoning...

MRCP revision battle 40.2: Carbon monoxide poisoning

Carbon monoxide has 200x more affinity for Hb than oxygen
This results in a left shift of the oxygen dissociation curve.



Normal levels of carboxyhaemoglobin are <3% in non-smokers or <10% in smokers.




In terms of carbon monoxide poisoning:

• 10-30% carboxyhaemoglobin = mild poisoning
• 30-60% = severe poisoning

Features of carbon monoxide poisoning are vague:

• 90% have a headache
• 50% nausea/vomiting
• 50% vertigo
• 30% confusion

Patients look pink


Severe CO poisoning can cause:

• fits
• coma
• cardiac arrrest/arrthymias
• pyrexia
• muscle necrosis
• acute renal failure
• increased reflexes and tone

Treatment is:

• 100% oxygen
• hyperbaric oxygen if LOC/pregnant/neuro signs - this decreases the half life from 4 hrs to around 22 minutes.

Next.... some pharmacology with acetylator status

MRCP revision battle 40.3: Acetylator status

Many drugs are metabolised in the liver by acetylation.  However, up to 50% of the UK population is deficient in hepatic N-acetyltransferase, meaning they are likely to accumulate drugs that require acetylation.  These patients are known as slow acetylators.


Drugs affected include (PS HID):

• procamide
• sulfasalazine
• hydrazaline
• isoniazid
• dapsone
• sulphonamides

Now for some generalised lympadenopathy....

MRCP revision battle 40.4: Generalised lymphadenopathy

Causes of generalised lymphadenopathy include:

• infective
• glandular fever
• HIV
• toxoplasmosis
• CMV
• rubella
• TB
• roseola infantum
• neoplastic
• leukaemia
• lymphoma
• drugs
• phenytoi
• allopurinol
• isoniazis
• rheumatological
• SLE
• RA
• sarcoidosis

After a dull list lets cover the sexier topic of acute mountain sickness....

MRCP revision battle 40.5: Acute mountain sickness, HAPE and HACE

Acute mountain sickness


Acute mountain sickness is usually a self-limiting condition.  

It tends to occur at altitudes higher than 2500m and develops gradually over 6 to 12 hours.

Symptoms are:

• headache
• nausea
• fatigue

Ironically, fitter people are more at risk.

Risk can be decreased by gaining altitude at no more than 500m/day
Acetazolamide (a carbonic anhydrase inhibitor) can also help prevent.


The treatment is to descend.



HAPE = High Altitude Pulmonary oEdema


HAPE presents like pulmonary oedema.


Treatment is:

• rapid descent
• nifedipine
• dexamethasone
• acetazolamide
• phosphodiesterase type V inhibitors (=tadalafil)

HACE = High Altitude Cerebral oEdema


This presents as headache, ataxia and papilloedema

Treatment is descent and dexamethasone.




Now for some trisomies....

MRCP revision battle 40.6: Trisomies - Down's, Edward's and Patau's

A trisomy is a genetic abnormality in which there are 3 copies of a chromosome instead of the usual 2.  It is a form of aneuploidy (=when the number of chromosomes is not a multiple of 23).


This battle will look at the 3 commonest trisomies in order of their frequency, which helpful is the same as the order of their names alphabetically.



Down's Syndrome = Trisomy 21

Causes of Down's:

• non-disjunction: 94%
• Robertson translocation: 5%
• mosaicism: 1%

Risk of Downs with age of mother:

• 30 yrs: 1/1000
• 35 yrs: 1/350
• 40 yrs: 1/100
• 45 yrs: 1/30

The characteristics of patients with Down's are varible but include:

• microgenia (=small chin)
• macroglossia
• epicanthic folds of eyes
• short neck
• single palmar crease
• flat nasal bridge
• low IQ
• short stature

Associations with Down's include:

• duodenal atresia
• Hirschsprungs disease
• AV septal defects (40%)
• ventricular septal defects (30%)
• atrial septal defects (10%)
• PDA/tetralogy of fallot
• Brushfield spots (=white spots on iris)

Later complications include:

• ALL
• atlantoaxial instability
• hypothyroidism

Edwards Syndrome = Trisomy 18


Characterised by:

• prominent occiput
• microcephaly
• overlapping fingers
• rockerbottom feet
• cardiac defects

Rare to survive beyond infancy




Patau's Syndrome = Trisomy 13

Characterised by:

• CNS, renal and cardiac abnormalities
• low IQ
• polydactyly
• rockerbottom feet

Rare to survive beyond infancy.



To the final battle of the day - hereditary angioedema

MRCP revision battle 40.7: Hereditary angioedema

Hereditary angioedema is an autosomal dominant condition in which a decrease in either the amount of C1 inhibitor or the function of C1 inhibitor results in swelling when the body is exposed to certain substances.


Attacks may be preceded by a painful macular rash.  The swelling may be life-threatening.  The image below from wiki commons (uploaded by Dr Heilman) shows a child with hereditary angioedema.

Increased levels of bradykinin play a central role in the pathphysiology and therefore ACE inhibitors (which prevent bradykinin breakdown) can cause angioedema.


Treatment acutely is with IV C1 inhibitor concentration. 
The anabolic steroid danozol may be given prophylactically as it increases liver C1 inhibitor production by an unknown mechanism.