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.