Question 36#

In the Gell and Coombs classification of hypersensitivity reactions scabies is an example of a: 

A. Type I reaction

Correct Answer D: Scabies produces a delayed type IV hypersensitivity reaction approximately one month after infestation. This produces the characteristic intense itching.

Hypersensitivity:
The Gell and Coombs classification divides hypersensitivity reactions into 4 types:
1- Type I - Anaphylactic: 

• Antigen reacts with IgE bound to mast cells
• Anaphylaxis, atopy

2- Type II - Cell bound:

• IgG or IgM binds to antigen on cell surface
• Autoimmune haemolytic anaemia, ITP, Goodpasture's

3- Type III - Immune complex:

• Free antigen and antibody (IgG, IgA) combine
• Serum sickness, systemic lupus erythematosus, post-streptococcal glomerulonephritis, extrinsic allergic alveolitis (especially acute phase)

4- Type IV - Delayed hypersensitivity:

• T cell mediated
• Tuberculosis, tuberculin skin reaction, graft versus host disease, allergic contact dermatitis, scabies, extrinsic allergic alveolitis (especially chronic phase)

In recent times a further category has been added:

5- Type V - Stimulated hypersensitivity:

• IgG antibodies stimulate cells they are directed against
• Graves', myasthenia gravis

Question 37#

Which one of the following electrolyte disturbances is most associated with the development of a prolonged QT interval on ECG?

A. Hyponatraemia

Correct Answer B: 

Long QT syndrome:
Long QT syndrome (LQTS) is an inherited condition associated with delayed repolarization of the ventricles. It is important to recognize as it may lead to ventricular tachycardia and can therefore cause collapse/sudden death.

The most common variants of LQTS (LQT1 & LQT2) are caused by defects in the alpha subunit of the slow delayed rectifier potassium channel. A normal corrected QT interval is less than 430 ms in males and 450 ms in females.

Causes of a prolonged QT interval:
 

Features:

• May be picked up on routine ECG or following family screening
• Long QT1 - usually associated with exertional syncope, often swimming
• Long QT2 - often associated with syncope occurring following emotional stress, exercise or auditory stimuli
• Long QT3 - events often occur at night or at rest
• sudden cardiac death

Management:

• Avoid drugs which prolong the QT interval and other precipitants if appropriate (e.g. Strenuous exercise)
• Beta-blockers***
• Implantable cardioverter defibrillators in high risk cases

*the usual mechanism by which drugs prolong the QT interval is blockage of potassium channels. See the link for more details.

**a non-sedating antihistamine and classic cause of prolonged QT in a patient, especially if also taking P450 enzyme inhibitor, e.g. Patient with a cold takes terfenadine and erythromycin at the same time.

***note sotalol may exacerbate long QT syndrome.

Question 38#

Which one of the following statements regarding mitochondrial inheritance is true?

A. Friedreich's ataxia is caused by defects in mitochondrial DNA

Correct Answer E: 

Mitochondrial diseases:
Whilst most DNA is found in the cell nucleus, a small amount of double-stranded DNA is present in the mitochondria. It encodes protein components of the respiratory chain and some special types of RNA.

Mitochondrial inheritance has the following characteristics:

• Inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
• All children of affected males will not inherit the disease
• All children of affected females will inherit it
• Generally encode rare neurological diseases
• Poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy)

Histology:

• Muscle biopsy classically shows 'red, ragged fibres' due to increased number of mitochondria

Examples include:

• Leber's optic atrophy
• MELAS syndrome: mitochondrial encephalo-myopathy lactic acidosis and stroke-like episodes
• MERRF syndrome: myoclonus epilepsy with ragged-red fibres
• Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
• Sensorineural hearing loss

Question 39#

A new drug designed to prevent exacerbations of genital herpes undergoes clinical trials. One hundred patients are given the new drug. During a three month period 10 of the patients have an episode of genital herpes. In the control group there are 300 patients who are given a placebo. In this group 50 people have an exacerbation during the same time period.

What is the relative risk of having an exacerbation of genital herpes whilst taking the new drug?

A. 0.8

Correct Answer D: 

• Experimental event rate, EER = 10 / 100 = 0.10
• Control event rate, CER = 50 / 300 = 0.166
• Therefore the relative risk = EER / CER = 0.1 / 0.166 = 0.6

Relative risk:
Relative risk (RR) is the ratio of risk in the experimental group (experimental event rate, EER) to risk in the control group (control event rate, CER). The term relative risk ratio is sometimes used instead of relative risk.

To recap:

• EER = rate at which events occur in the experimental group
• CER = rate at which events occur in the control group

For example, if we look at a trial comparing the use of paracetamol for dysmenorrhoea compared to placebo we may get the following results:

• Experimental event rate, EER = 60 / 100 = 0.6
• Control event rate, CER = 20 / 80 = 0.25
• Therefore the relative risk ratio = EER / CER = 0.6 / 0.25 = 2.4

If the risk ratio is > 1 then the rate of an event (in this case experiencing significant pain relief) is increased compared to controls. It is therefore appropriate to calculate the relative risk increase if necessary (see below).

If the risk ratio is < 1 then the rate of an event is decreased compared to controls. The relative risk reduction should therefore be calculated (see below).

Relative risk reduction (RRR) or relative risk increase (RRI) is calculated by dividing the absolute risk change by the control event rate:

• Using the above data, RRI = (EER - CER) / CER = (0.6 - 0.25) / 0.25 = 1.4 = 140%

Question 40#

Which one of the following statements regarding nitric oxide is incorrect?

A. Promotes platelet aggregation

Correct Answer A: Nitric oxide - vasodilation + inhibits platelet aggregation.

Nitric oxide inhibits, rather than promotes, platelet aggregation.

Nitric oxide:
Previously known as endothelium derived relaxation factor, nitric oxide (NO) has emerged as a molecule which is integral to many physiological and pathological processes. It is formed from Larginine and oxygen by nitric oxide synthetase (NOS). An inducible form of NOS has been shown to be present in macrophages. Nitric oxide has a very short half-life (seconds), being inactivated by oxygen free radicals.

Effects:

• Acts on guanylate cyclase leading to raised intracellular cGMP levels and therefore decreasing Ca2+ levels
• Vasodilation, mainly venodilation
• Inhibits platelet aggregation

Clinical relevance:

• Underproduction of NO is implicated in hypertrophic pyloric stenosis
• Lack of NO is thought to promote atherosclerosis
• In sepsis increased levels of NO contribute to septic shock
• Organic nitrates (metabolism produces NO) is widely used to treat cardiovascular disease (e.g. angina, heart failure)
• Sildenafil is thought to potentiate the action of NO on penile smooth muscle and is used in the treatment of erectile dysfunctions