Thursday 11 November 2010

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.

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

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

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

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

  • 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

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