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.

MRCP revision battle 39.1: Hodgkin's Lymphoma

Its the second day of haematology fun!  Lets dive straight in...


MRCP revision battle 39.1: Hodgkin's Lymphoma
MRCP revision battle 39.2: Non-Hodgkin's lymphoma
MRCP revision battle 39.3: Systemic mastocytosis
MRCP revision battle 39.4: Thrombocytosis
MRCP revision battle 39.5: Haemophilia
MRCP revision battle 39.6: The spleen
MRCP revision battle 39.7: Autoimmune haemolytic anaemia





MRCP revision battle 39.1: Hodgkin's Lymphoma


Lymphomas are malignant proliferations of lymphocytes.  These may accumulate in lymph nodes, in organs or in the peripheral blood.


Lymphomas are divided into 2 main types: Hodgkin's, which has characteristic Reed-Sternberg cells, and non-Hodgkin's, which do not have Reed-Sternberg cells.

The slide below (by Dr Ed Uthman) shows a Reed-Sternberg cell in the centre with its characteristic mirror-image nuclei:

Staging of Hodgkin's lymphoma is done by the Ann Arbor system:

• I = one lymph node group
• II = 2 areas on one side of the diaphragm
• III = both sides of the diaphragm
• IV = extra-nodal tissues (NB the spleen is counted as an 'honorary' node)

Each stage is subdivided into A or B:

• A = no B symptoms
• B =  T>38c, night sweats or weight loss >10% in 6 months

Pel Ebstein fever = cyclical fever with long periods of normal temperature - is so rare some believe it to be mythical...


Pruritus or alcohol-induced pain are not B symptoms bit are useful indicators of relapse.


Poor prognostic factors are:

• B symptoms
• stage IV
• Hb <10.5
• lymphocyte count <8%
• male

 Histological subtypes of Hodgkin's lymphoma are:

• nodular sclerosing = most common, good prognosis
• mixed cellularity - good prognosis
• lymphocytic predominant = best prognosis
• lymphocytic depleated = least common, worst prognosis

Bloods will show:

• neutrophilia
• anaemia
• thrombocytosis
• raised ESR
• raised LDH - a useful guide to the bulk of the disease

Treatment is with radiotherapy, chemotherapy (ABVD) or both.


Now on to non-Hodgkin's lymphoma...

MRCP revision battle 39.2: Non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma are a hugely diverse group of diseases and this battle is a highly edited set of highlights for MRCP revision.


Low grade 

• relatively mature cells
• indolent but usually incurable
• try local radiotherapy

High grade

• immature cells
• rapidly progressive disease but 40% curable
• treated with CHOP chemo
• includes Burkitts lymphoma

B cell lymphoma

• treated with rituximab

Lymphoblastic

• treated as ALL

Now for a short battle with an esoteric condition...

MRCP revision battle 39.3: Systemic mastocytosis

Systemic mastocytosis is a neoplastic proliferation of mast cells.


Features include:

• flushing
• abdominal pain
• monocytosis on blood film
• urticaria pigmentosa (Darier's sign)

It is diagnosed by raised serum tryptase and urinary histamine


It is vanishingly rare in real life.


So from something very rare to very common: thrombocytosis

MRCP revision battle 39.4: Thrombocytosis

Thrombocytosis = raised number of platelets.




Primary = essential thrombocythaemia

• caused by a clonal proliferation of megakaryocytes
• platelets typically >1000 (x10 to the power 9)
• abnormal function, risking either thrombosis or bleeding
• treatment = aspirin.  Hydroxycarbamide is given to lower platelets if pt is >60yrs or they have had a previous thrombosis

Secondary thrombocytosis

• reactive to
• bleeding
• infection
• trauma
• thrombosis
• infarction
• iron deficiency

Now for some haemophilia....

MRCP revision battle 39.5: Haemophilia

Haemophilia A and Haemophilia B clinically present very similarly, with bleeds into joints and muscles.

Both are inherited in an X-linked recessive way but 1/3 of cases will have no family history.

Both cause raised aPTT.


Haemophilia A = lack of factor VIII
Haemophilia B = lack of factor IX = Christmas disease


Treatment is with desmopressin and tranexamic acid.  Major bleeds may need recombinant factor VIII.  Avoid NSAIDs and IM injections.



On to an organ that has always bewildered me... the spleen

MRCP revision battle 39.6: The spleen

My dubious relationship with the spleen goes waaayyy back to medical school anatomy days when I learnt that any mass of tissue that I had absolutely no idea what it was when placed on a tray in front of me was usually a spleen.


The spleen was equally mysterious to the medical profession in general for many years, as no-one was quite sure as to its function.  It is now known to act as a reservoir for lymphocytes and so is vital in dealing with bacteraemias.


This battle will look at the 2 extremes of spleen: splenomegaly, and hyposplenism/post splenectomy.



Splenomegaly

Massive splenomegaly can occur in:

• CML
• myelofibrosis
• malaria
• leishmaniasis
• Gaucher's syndrome (= an inherited lysosomal storage disease)

Moderate splenomegaly can occur in:

• infections: typhoid, brucella, TB, glandular fever, EBV, schistosomiasis
• haematological disorders: lymphoma, leukaemia, haemolytic anaemia
• connective tissue disease: SLE, RA
• portal hypertension: cirrhosis, CCF

Splenectomy

Splenectomy is performed for a variety of reasons including:

• trauna
• ITP
• warm AIHA

2 weeks prior to splenectomy pneumoccal vaccine and HiB should be given; if the splenectomy is an emergency these should be given ASAP afterwards.
Lifelong penicillin (or erythromycin if penicillin allergic) is then also needed.


Most common serious infections after splenectomy are from encapsulated organisms such as s.pneumoniae, h.influenzae and n.meningitidis.


Blood film after splenectomy shows:

• Howell-Jolly bodies (=nuclear remnants in RBCs)
• target cells
• Pappenheimer bodies (=abnormal iron inside RBCs)

There is low IgM.


As well as hyposplenism being a problem post splenectomy, it can also occur in sickle cell disease, coeliac disease and myeloproliferative diseases



Now onwards to some AIHA...

MRCP revision battle 39.7: Autoimmune haemolytic anaemia

Autoimmune haemolytic anaemia (AIHA) is mediated by autoantibodies and results in mainly extravascular haemolysis.

AIHA will result in a positive direct antiglobulin test (= positive Coombs test)


AIHA is divided depending on the optimal binding temperatures of the autoantibodies to the RBCs.



Warm AIHA = 37C

• Ig G
• SLE, lymphoma, CLL, methyl dopa
• treatment: steroids, immunosupression, splenectomy

Cold AIHA = 4C 

• IgM
• lymphoma, mycoplasma, EBV
• treatment: keep warm, ?chlorambucil

MRCP revision battle 38.1: Von Willebrands Disease

We're about to enter a 2 day fest of haematology.  Try to get through the dull battles of B and T cell disorders as the topics on the other side of them are slightly more stimulating.  Good luck!


MRCP revision battle 38.1: Von Willebrands Disease
MRCP revision battle 38.2: B cell disorders
MRCP revision battle 38.3: T cell disorders
MRCP revision battle 38.4: Combined B and T cell disorders
MRCP revision battle 38.5: Thrombotic thrombocytopenic purpura
MRCP revision battle 38.6: Microangiopathic haemolytic anaemia
MRCP revision battle 38.7: Sideroblastic anaemia




MRCP revision battle 38.1: Von Willebrands Disease


Von Willebrand's disease is the commonest inherited coagulopathy in the UK.


Von Willebrand's factor is a substance made in epithelial cells which:

• helps platelets bind to the exposed subendothelium
• helps platelets bind to each other
• binds to factor VIII,  helping prevent its destruction in the circulation

There are many types of Von Willebrand's disease.  The commonest 3 are:

• Type 1: decrease in Von Willebrand's factor 
• accounts for 80% of Von Willebrand Disease
• autosomal dominant
• Type 2: abnormal form of Von Willebrand's factor
• autosomal dominant
• Type 3: total lack of Von Willebrand's factor
• autosomal recessive

Symptoms/signs of Von Willebrand's disease include bruising, menorrhagia, epistaxis and increased bleeding after tooth extraction (a favourite in MRCP exams)


Diagnosis is by:

• low levels factor VIII
• low levels VWF antigen
• deficient ristocetin-induced platelet aggregation

Treatment is:

• DDVAP (=desmopressin) in mild disease
• factor VIII concentrate/cryoprecipitate in severe disease
• avoid NSAIDs.

Next up.... B cell disorders