Smoking Cessation

Currently, 16.6 % of australians aged 14 years or older smoke daily. This represents 2.9 millions people in australia, one in two of whom will die prematurely from a smoking related disease if they continue to smoke.

Counseling about cessation of smoking behaviour involves six stages:

• Pre-contemplation
• Contemplation
• Determination
• Action
• Maintenance
• Relapse

The role of a doctor to find out which stages the patients are at and to give information and support to achieve the smoking cessation.

Once the patients are determined to stop smoking, pharmacotherapy should be offered to the nicotine dependent smokers.

Method: The most popular method used is the cold turkey method - quitting abruptly with no medication or assistance.

Only 3 - 5 % of smokers who try to quit without treatment remain abstinent six to 12 months later.

Cut down then stop method is a new strategy for smokers who are not currently willing or able to stop smoking but are prepared to cut down. Smoker gradually cut down their cigarette use and stop smoking completely by six months and then nicotine replacement therapy is ceased by 12 months.

Australian and international guidelines now advise using medication to assist quitting in all smokers who are nicotine
dependent, except where indicated.

To assess the nicotine dependence the patients should be asked:

• Do you usually smoke within 30 minutes of waking?
• Do you smoke between 10 and 15 or more cigarettes per day?
• Have you had cravings or withdrawl symptoms during previous quit attempts?

Nicotine dependence is likely if there is a positive answer to any of these questions.

Nicotine Replacement therapy

• Pre-quit treatment with nicotine patches two weeks before quit day.
• Nicotine patches are then continued for the full course of 10 to 14 weeks after quit day.
• Quick acting forms of NRT such as lozenges and chewing gum are suitable for prompt relief of withdrawl symptoms or cravings as they arise.

Varenicline: reduces cravings and withdrawl symptoms as other treatment do but also reduces satisfaction gained from smoking a cigarette.
Varenicline is taken as a 12 weeks course of 1 mg twice a day after an initial one week titration phase. The patient should quit smoking between seven and 10 days after the first dose.
Side effects include nausea, depression and suicidal ideation.

Bupropion: is an effective first line therapy. There is a one in 1000 risk of seizures in patients taking it and it is contraindicated in patients with predisposing risk factors for seizures.

Obesity

Not all obese people eat more than the average person, but all obviously eat more than they need!

Obesity is a leading preventable cause of death worldwide, with increasing prevalence in adults and children, and it is viewed as one of the most serious public health problems of the 21st century. Obesity is stigmatized in the modern western world, though it has been perceived as a symbol of wealth and fertility at other times in history, and still is in many parts of Africa.

WHO Classification:
Overweight - BMI 25 - 30.
Obese
Class I / moderate - BMI 30 - 35
Class II / severe - BMI 35 - 40
Class III/ very severe - BMI more than 40

Aetiology:

• Genetics
• Endocrine - hypothyroidism, Cushing's syndrome and growth hormone deficiency
• Obstructive sleep apnoea
  
• Life style - sedentary habit, increased calorie intake

Morbidity and Mortality associated with obesity:

• Psychological
• CVA
• Cardiovascular: Hypertension, IHD, PVD and heart failure
• Respiratory: OSA/OHS
• Gatroenterology: hiatus hernia, fatty liver, gall stones
• Endocrine: diabetes, hyperlipidaemia
• Musculoskeletal: back pain, osteoarthritis, varicose vein and recurrent cellulitis.

Treatment of Obesity:

It should be divided into initial weight loss phase and long term maintenance phase.
Initial weight loss phase:

Increasing energy expenditure:

• Unfortunately increased physical activity alone with no change in food intake is associated with only moderate weight reduction.
• Many patients simply compensate for increased activity by increasing their food intake.
• Commercial weight loss program are available.

Reducing energy intake:
Life Style changes:

• Food chart
• Dietician advices about reducing portion of food intake and change in energy density of food
• Psychological method such as distraction away from food

Pharmacological methods:

Sibutramine is a noradrenaline and serotonin reuptake inhibito that acts centrally to increase satiety while increasing energy expenditure. It is available as 10 mg or 15 mg dose.
It side effects include insomnia, agitation and constipation as well as slight increase in blood pressure.

Orlistat is a lipase inhibitor acting in the intestine to decrease the absorption of fat by approximately 30 %. Its side effects include flatulence, bloating or other gastrointestinal effects.

Sertraline and fluoxetine are not licensed for the management of obesity but they can be of particular benefit in patients with mild depression or with obsessive thoughts regarding food intake. For many patients these drugs can limit the sense of deprivation associated with dieting.

Non-pharmacological methods:

Although patients with simple obesity ( BMI between 30 - 40 ) can lose weight using many different techniques, those with morbid obesity has many limitations including poor mobility.

Patients with extreme morbid obesity ( BMI > 50 ) have great difficulty walking more than 2000 steps a day.

Three non-pharmacological methods are currently used:

Very low calorie diets - optifast

• Optifast three meals per day replacement take in fewer than 800 calories per dya yet do not feel hunger because they produce ketones. It is also used in Australia to reduce liver size prior to a laproscopic gastric band procedure.

Intragastric balloon is beneficial for in obese patients with lower BMI ( 30 - 35 ) who do not fit the criteria for a laproscopic gastric banding procedure.

Bariatric surgery - either restrictive or malabsorptive or both.

• Indications: BMI > 40 or BMI > 35 with complications such as DM, IHD, Hypertension or sleep apnoea.

Maintenance phase:

A new concept of weight maintenance is the idea of a trigger weight.

Patient try to maintain their weight by reducing energy intake and increasing their energy expenditure. Once they hit above the trigger weight, they come back for the initial successful methods of weight loss.

Erectile Dysfunction

Erectile dysfunction is the most common sexual problem in men.

Erectile dysfunction is the inability to achieve and maintain an erection of sufficient rigidity for satisfactory sexual intercourse.

Causes:

• Endocrine: hypogonadism, thyroid disease
  
• Vascular such as smoker, IHD, PVD and CVA patients
• Neurogenic: autonomic neuropathy such as diabetes
• Drugs such as beta blocker
• Psychogenic: such as depression and anxiety

Management:
History

• Presence of nocturnal emission and frequent satisfactory morning erections makes endocrine disease unlikely.
• Review past medical history and drug chart.
• Five - Item Version of the International Index of Erectile Function Questionnaire

http://www.medal.org/OnlineCalculators/ch16/ch16.09/ch16.09.07.php

Physical examination

• External genitalia examination
• Check for peripheral pulses.

Investigations

• Blood test: FBC, UE, LFT, PSA, morning total testosterone, gonadotrophins and prolactin level and thyroid function test.

Treatment:
Non-pharmacological - such as removal of offending drugs, cessation of smoking and Vaccum device.
Pharmacological -
Modify the reversible causes such as replacement of testosterone, treatment of thyroid disorder.
Drugs
First line - Phosphodiesterase inhibitor such as sildenafil, tadalafil and vardanefil. However, they are contraindicated in patients who use the nitrate therapy.
Second line - intracorporal injection of vasodilator such as alprostadil.

Polycythemia

Polycythemia vera is a myeloproliferative disorder that need to be distinguished from other causes of increased haemoglobin level such as:

• Smoker's polycythemia
• Relative polycythemia - dehydration
• Secondary polycythemia - such as hypoxia, renal cell cancer which produces erythropoietin

In 2005, the JAK2-V617F mutation was described in the JAK2 gene. This mutation occurs in about 95% of patients with polycythemia vera. This mutation can also occurs in other myleproliferative disorders such as primary myelofibrosis or essential thrombocythemia, although they do not occur in the general population.

As a result, Current WHO diagnostic criteria was adjusted for the diagnosis of polycythemia vera as follows:

The presence of both major criteria and at least one minor criteria or the first major criteria and at least two minor criteria is required for a diagnosis of polycythemia vera.

The major criteria are:

1. Raised Haemoglobin lvel, haematocrit or red cell count
2. the presence of JAK2 gene

The minor criteria are:

• typical bone marrow histology
• low serum erythropoietin level
• formation of endogenous erythroid colonies on marrow culture

Diagnositic Algorithm:

If high haemoglobin level is found, repeat the haemoglobin test to determine if the raised level is borderline or transient.

If haemotocrit is less than or equal to 0.54 in men or 0.47 in women:
Consider causes other than polycythemia vera.

If haemotocrit is more than 0.54 in men or 0.47 in women:

• Firstly check oxygen satuation level, if less than 92% then it is likely due to secondary cause.
• If it is more than 92%, check for JAK2 gene mutation, erythropoietin level and/or bone marrow biopsy.
  

Diagnosis and Treatment of hepatocellular carcinoma ( HCC )

Risk factors:

HCC is unusual among human cancers in that the etiological agent responsible is usually readily identifiable. The prevalence of HCC worldwide parallels that of viral hepatitis. Alcohol, genetic haemochromatosis and rarely primary biliary cirrhosis are associated.
The risk of HCC development is much greater in men for the majority of aetiologies.
Cirrhosis is present in the vast majority of patients with HCC in the UK and europe: estimates varies between 90 % and 95 %. It is unclear if cirrhosis per se is biologically important in the tumorigenic pathway, or if tumour development and fibrogenesis take place concurrently but with fibrosis taking a shorter time period.
Non-cirrhotic HCC occur in the young patients ( fibrolamellar variant ) and in the elderly ( apparent de novo HCC )

Natural History of HCC:

• The estimated doubling time is one to 19 months with a median of 6 months.
• 50 - 90 % of patients with Child Pugh A cirrhosis will survive a year untreated with only 20 % of Child Pugh C patients.
• Smaller HCC at presentation have realtively long tumor doubling time and overall survival with tumour size less than 5 cm was 81 -100 % at one year and 17 - 21% at three year with no therapy.

Screening:

As per British Gastroenterology guidelines, surveillance for hepatocellular carcinoma should be considered in the following high risk groups:

1. Male and Female with established cirrhosis due to hepatitis B virus, particularly those with ongoing viral replication.
2. Male and Female with established cirrhosis due to HCV.
3. Male and Female with established cirrhosis due to genetic haemochromatosis.
4. Male with alcohol related cirrhosis who are abstinent from alcohol or likely to comply with treatment
5. Male with cirrhosis due to primary biliary cirrhosis.

The risk of HCC development in cirrhosis due to autoimmune hepatitis, primary sclerosing cholangitis in both sexes, and alcoholic and primary biliary cirrhosis in women is generally low.

If the surveillance is offered, it should be six monthly abdominal ultrasound assessments in combination with serum alpha feto protein estimation.

AFP, a normal serum protein synthesised by fetal liver cells and yolk sac cells, is the most widely used screening test for HCC. The normal range for AFP is 10 - 20 ng/ml and a level > 400 ng/ml is usually regarded as diagnostic. Two thirds of HCC less than 4 cm however has AFP levels less than 200 ng/ml and up to 20 % of HCC do not produce AFP, even when very large. A rising AFT over time, even if the levels does not reach 400 ng/ml is virtually diagnostic of HCC.

Diagnosis of HCC:

When a patient presents with a liver mass, irrespective of screening, there is a requirement to make a diagnosis and to stage the disease.

If the patient known to have pre-existing cirrhosis:

A mass greater than 2 cm has 95 % chance of being HCC.
- If the AFP is raised, this confirms the diagnosis and further investigation is only required to establish the most appropriate therapy.
- If the AFP is normal, further imaging ( CT/MRI or lipoidol angiography with follow up CT) will usually allow a confident diagnosis to be made.
- In a very few cases where there is real diagnosis in doubt, biopsy may be indicated.

A mass less than 2 cm on ultrasound, probably 75 % of such nodules turn out to be HCC. Again radiological diagnosis CT/MRI and AFP may establish a definitive diagnosis. If not either a repeat examination to show enlargement of the lesion, percutaneous fine needle aspiration, or biopsy may be indicated.

The risk of seedling of tumor in the needle tract occurs in 1 - 3 %. Biopsy of potentially operable lesions should be avoided where possible.

Treatment of HCC:

Surgical Methods:
The only proven potentially curative therapy for HCC remains surgical, either hepatic resection or liver transplatation, and patients with single small HCC ( less than 5 cm ) or up to three lesions less than 3 cm should be referred for assessments of these treatment modalities.

• Liver transplantation should be considered in any patient with cirrhosis.
• Hepatic resection should be considered as primary therapy in any patient with HCC and a non-cirrhotic liver.
• Hepatic resection can be carried out in highly selective patients with hepatic cirrhosis and well preserved hepatic function ( Child-Pugh A) who are unsuitable for liver transplantation.
• Patients with replicating HBV had a worse outlook due to HBV recurrence and were previously not considered candidates for transplantation. Effective antiviral therapy is now available and patients with small HCC, as defined above should be assessed for transplantation.

Non-surgical methods:

Non-surgical methods should only be used where surgical therapy is not possible.

• Percutaneous Ethanol injection ( PEI ) has been shown to produce necrosis of small HCC. It is best suited to peripheral lesions, less than 3 cm in diameter.
• Chemoembolisation
• Systemic chemotherapy with standard agents has a poor response rate.
• Hormonal therapy with tamoxifen has shown no survival beneift.

What a pain!

Pain management ( of Non-malignant cause )is still a very much more of an art than a science and those who like black and white solution to clinical problem will be disappointed.

Acute Pain
Acute pain, associated with trauma or surgery, is generally easier to manage than chronic pain. This is because the type of pain is usually related to form of tissue damage resulting in excitation of nociceptor nerve endings. Few would deny that the use of potent opioid drugs in these circumstances is worthwhile.

Chronic Pain
Chronic pain is defined as pain lasting more than three months which is the upper limit of normal time for wound healing. Patients experiencing pain do not present with objective signs or symptoms as they would with high blood pressure or a raised blood glucose level.

There are three types of pain behaviour:

• Nociceptive pain due to excitation of mechanical, thermal or chemical nociceptors
• Neuropathic pain, defined as pain related to disease or injury of the peripheral or central nervous system
• Pain disorders that exist when it is not possible to explain the patient's symptoms on a physical basis. Pain disorder can be subconscious ( conversion disorder ) or conscious ( malingering ).

Management:
Non-pharmacological treatment plays an essential role in the management of chronic or persistent pain.
Firstly, it is important to reassure the patient that there is no serious underlying pathology, giving a simple but understandable explanation of the causes of pain.

It is recognised that because of a patient pressure a request for an X-ray or CT scan will usually be made. A careful explanation of these findings are needed because patients may interpret relatively benign reports in an alarmist way, further reinforcing abnormal beliefs about the cause of their pain.

Secondly, patient expectation need to be addressed to ensure that they are realistic. For many patients, whether they have nonspecific pain issues or specific but not otherwise treatable conditions, resolution of all pain symptoms is often impossible and patient's expectations need to reflect this. However, it is important to emphasie that despite pain, an improvement in function and quality of life is still possible.

Thirdly, Unlike acute pain management, physiotherapy is important to rehabilitate the patient and bed rest must be discouraged. The major aim of the whole management program is to improve activity and functional status of patients with the hoping returning back to usual employment.

Excessive reliance on passive coping strategies such as medication should be discouraged. Often patients with chronic pain are deconditioned and has high BMI due to psychological problem, unhealthy life style and lack of movement due to pain.

Fourthly, It is important to address the patient's psychosocial problems.

Due to persistent pain, many of these patients are unemployed, on disability pension adding to financial burden. They are therefore prone to suffer anxiety, depression and low self esteem.
Moreover, they are more likely to be socially isolated and has unhealthy life style such as smoking and drinking leading to cardiopulmonary diseases.

Psychologist referral should be made for cognitive behaviour therapy for the patient to be able to cope with the pain and related psychological problem. If low mood is detected, then use of antidepressant such as SSRI should be considered.

Despite the best efforts, some patients seem to rely soley on mediations and fail to engage in an appropriate rehabilitation program. These patients are sometimes referred to as ''chemical copers''. Management of these patients should involve clearly set boundaries, especially with regard to request for extra medication. Care should be taken to avoid unnecessary investigations, referrals and treatements. Significant support is required from the treating doctors, as well as allied health professionals, family and community services.

Pharmacological treatment:
Recent meta-analysis demonstrate a modest reduction in pain with dosages of upto 100 mg per day of morphine equivalent but this is not always accompanied by improved function. There is some agreement that in patients already receiving regular opioid medication for persistent pain, a ceiling for the total daily dose should be considered. Some authorities have suggested a ceiling of 100 mg per day morphine equivalents.

Surgery is no panacea and it may provide some temporary relief from pain such as facet joint injection in chronic back pain.

For neuropathic pain, first line medication is tricyclic antidepressant and if they are unable to tolerate it then pregabalin or gabapentin are recommended. Second line agents include anticonvulsant such as valporate or carbamazepine and serotonin noradrenaline reuptake inhibitor.

Ankylosing Spondylitis

Ankylosing spondylitis is a progressive rheumatological disease, which is difficult to diagnose early and even more difficult to treat.

It is a member of the group of the spondyloarthropathies which includes reactive arthritis ( previously known as Reiter's syndrome ), psoriatic arthritis, inflammatory bowel disease-related spondyloarthritis and undifferentiated SpA. The shared features of this group are:

• Inflammatory arthritis in a characteristic pattern, often of the sacroiliac joints and / or the axial skeleton.
• Asymmetric peripheral joint involvement, usually in the lower limbs
• Inflammation of ligament or tendon insertions ( enthesitis )
• An association with the presence of HLA-B27
• A higher incidence of uveitis and psoriasis

Diagnosing ankylosing spondylitis:

It is more common in men than women and usual onset is at 20 - 30 years.

Chronic back pain is common which is inflammatory in nature in 5 % of younger patients. It is useful to note that 50% of inflammatory back pain are due to AS. The current definition for inflammatory back pain is:

• Onset in patients aged less than 50 years
• Chronic back pain of greater than three months' duration; plus two or more of the followings:

-morning stiffness lasting longer than 30 minutes
-pain and stiffness relieved with exercise but not with rest
-alternating buttock pain
-being awoken by pain in the second half of the night

In the setting of inflammatory back pain the presence of any of the additional features makes the diagnosis of AS more likely.

• History of uveitis/inflammatory bowel disease/family history
• Restricted spinal movements
• Sacroilitis
• Pulmonary fibrosis/cardiac involvement

Response to NSAIDs can lend you further support for a diagnosis of inflammatory back pain. Approximately 75% of patients with inflammatory back pain will find some relief from pain within 48 hrs of regular NSAID use whereas only 15 % of those with mechanical back pain will similarly find relief.

There are small number of people who do not respond to NSAID or are contraindicated to NSAID and they have poorer prognosis.

Investigation:

Radiological changes: According to New York Criteria from 1984, a patient is classified as having AS if he or she has a definite radiographic sacroiliitis plus one of the following:

• Inflammatory back pain
• limitation of range of movement in hte lumbar spine in the saggital and frontal planes
• limited chest expansion

Sacroilitis can be graded from one to four from a plain X-ray and a diagnosis of AS requires either bilateral grade two changes or unilateral grade three changes.

Inflammatory markers are not useful for diagnosis of AS. 40% of people with AS will never have an elevated CRP/ESR level. However, in patients who has elevated inflammatory markers, changes in levels may reflect changes in disease activity. Persistent elevation in markers seem to reflect a worse prognosis.

HLAB-27: The diagnosis of AS relies on clinical evaluation and radiological findings. Only one blood test can add further weight to the diagnosis and that is the test for surface antigen HLAB-27. This test has a reported sensitivity and specificity of 90%.

Management:
Physiotherapy is universally accepted part of the mangement of any patient with AS.
NSAID are the first line drug therapy for all patients with AS. It improves axial and peripheral pain, as well stiffness and overall function.
Corticosteroid: for patients with extra-axial symptoms, corticosteroid injections are useful for enthesitis and peripheral arthritis.

Patients with peripheral arthritis may be managed with sulfasalazine but methotrexate and leflunamide has very little evidence to be used.

TNF-alpha inhibitors: Infliximab, Etanercept and Adalimumab

Patients with AS who failed to respond to NSAIDs may require treatment with TNF-alpha inhibitors. The clinical response to TNF alpha inhibitor is quite rapid. The degree of improvement is related to the duration of the disease before treatment: the earlier it is treated the greater the potential response.

TNF - alpha inhibitor is not without significant complications. They are contraindicated in active infection and may increase the rate of tuberculosis.

Before TNF-alpha inhibitors are prescribed to patients with AS, it is recommended that patients are screen for latent tuberculosis.

Etanercept has been associated with an exacerbation of Crohn's disease and adalimumab with development of SLE. Infliximab has been associated with development of psoriasis, peripheral arthritis, SLE and vasculitis.

Criterial for eligibility of PBS benefit for TNF-alpha inhibitors:

• Documented X ray evidence of sacroilitis
• At least two of the following three criteria:

-Inflammatory back pain
-Reduced chest expansion
-Reduced lumbar mobility

• Elevated level of ESR > 25 mm or CRP >15
• Failed a minimum three-month trial of two different NSAIDs in conjunction with an appropriate program
• A Bath Akylosing Spondylitis Disease Activity Index of at least four.
• Completed appropriate concomitant exercise program.

Haemochromatosis

Hereditary haemochromatosis is a common inherited disorder in which excessive iron absorption may lead to increased body iron stores with deposition of iron in parenchymal cells of the liver, heart, pancreas and other organ.

Disorder other than hereditary haemochromatosis which give rise to iron overload are classified under the broad heading of secondary iron overload syndrome.

Genetics of hereditary haemochromatosis:
Significant iron overloading occurs principally in C282Y homozyotes and occassionally in C282Y/H63D compound heterozygotes. Other HFE genotypes including heterozygosity for C282Y, usually do not develop significant iron overload.

Screening and Diagnosis:
The approach to testing for haemochromatosis may be summarised as follows:
1. In people without family history of HFE

• The transferrin satuation and serum ferritin concentration are the most useful screening tests. The transferrin saturation is more sensitive in detecting early iron overload.
• These tests should be done in the morning after an overnight fast.
• If the fasting transferrin saturation is greater than 45%, the measurement should be repeated and if it remains elevated the HFE gene test should be performed. The ferritin level may also be elevated in patients with haemochromatosis but there are many other causes of elevated ferritin.

2. All first degree relatives of the index case should be screened by testing for mutation in HFE gene. It has been recommended that genetic testing for HFE within families occur during adolescence.

3. Since the discovery of HFE gene, liver biopsy is no longer necessary to diagnose HFE. However, liver biopsy is necessary to establish the presence of cirrhosis and should be considered when there is a history of significant alcohol intake, hepatomegaly on clinical examination, liver enzymes are raised or the serum ferritin is more than 1000 ug/L.

Treatment: consists of life long venesection therapy.

The initial course is one or two venesectin per week until the excess iron stores are removed. Once this is achieved patients usually require one venesection every 3-4 months to keep iron stores at low normal levels.

However, patients with severe cardiac disease may not tolerate venesection and these patients may be given iron chelation therapy with desferrioxamine.

It is the usual practice that cirrhotic patient should undergo HCC surveillance every six months with hepatic USS and serum alpha-fetoprotein measurement.

Fibromyalgia

Fibromyalgia is a common cause of chronic musculoskeletal pain. Fibromyalgia is caused by abnormal processing of pain mechanisms within the brain and the spinal cord.

The recommended diagnostic criteria were quite simple:

• Widespread musculoskeletal pain
• Excess tenderness in at least 11 of 18 predefined anatomic sites . Excess tenderness is defined by an abnormally low threshold for pain is considered to be present in a patient when pain is elicited at a tender point from pressure that blanches the finger nail.

Other features includes:

• Muscle tightness, often noted as muscle co-contraction or give way wekness.
• Dermatographia
• Non-anatomical sensory symptoms ( numbness, pins and needles, numbness and burning )

Although the diagnosis of fibromyalgia is usually straightforward the condition often co-exists with other conditions and presenting symptoms may be similar. Reg flags must always be considered and if present, it requires to investigate further.

• Older age at new symptom onset
• Weight loss
• Fever or night sweat
• Focal pain
• Night pain
• Neurological features
• History of malignancy

Investigation that may be required for initial work up includes: FBC, U&E, LFT, CRP, ESR, CK, TFT, Vitamin D level, Rheumatoid factor and antinuclear antibody.

Management:

Education, exercise and psychological strategies must be initiated in all patients with fibromyalgia. The importance of these measures cannot be overemphasized.

Analgesia
Paracetamol: is often not effective.
NSAIDs: may help some patients.
Opiods: in general pure opioid mediations are not clinically useful in the sensitised pain system that characterises fibromyalgia. There are no available trials of pure opioid medication use. Tramadol has combined opioid and serotonin noradrenaline reuptake inhibitory action, and it has been shown to be effective in pain control and improves function in patient with fibromyalgia.
Pain System Modulator: Tricyclic antidepressants and Serotonin Noradrenaline reuptake inhibitors are now more frequently used. However, SSRI has much less effective in management of fibromyalgia.

Coeliac Disease

Coeliac disease is a common and often unrecognised disorder that reportedly occurs in up to one in 100 individuals. Both caucasians and non-caucasians are affected but it is extremely rare in chinese, japanese and Afro-Caribbean people.

Pathogenesis and Genetics:
Coeliac disease results from both cell-mediated and humoral responses to ingested gluten. HLA -DQ2 is found in up to 95 % of patients with coeliac while nearly all the remaining population possess HLA-DQ8.

Clinical manifestations:
The classic presentation in infants ( diarrhoea, steatorrhoea, failure to thrive, weight loss and abdominal distension ) is rarely seen now. In recent times, there has been an increasing awareness of more subtle presentations in adults, including:

• Fatigue resulting from anaemia secondary to iron and/or folate deficiency
• Osteopenic bone disease
• Non-specific gastrointestinal symptoms often mimicking irritable bowel syndrome ( bloating, abdominal pain and bowel irregularity )
• Menstrual abnormalities such as late menarche, early menopause and reduced fertility, still birth, recurrent miscarriage
• In men, abnormalities in sperm motility and morphology can result in infertility.

Associated conditions:

• Hyposplenism
• Autoimmune disease such as type I DM, autoimmune thyroid disease, primary biliary cirrhosis and Sjogren's dyndrome.
• Dermatitis herpetiformis
• Increased risk for lymphomas and gastrointestinal malignancies.

Diagnosis:
A gluten free diet is not only expensive but also often tedious and hence a high price to pay for a person who does not suffer from the condition. So it is important to confirm the diagnosis before labelling an individual as having coeliac disease.

Serological testing: four serological tests are available ( IgA tTG antibody, IgA endomysial antibody, IgA antigliadin antibody and IgG antigliadin antibody ). IgA tTG antibody test a sensitivity greater than 95% and a specificity in the range of 90-96%. Antigliadin test has lower diagnostic accuracy than the IgA tTG antibody and anti endomysial antibody test. However, 2-3 % of individuals with coeliac disease have selective IgA deficiency, and so IgA levels should be measureed at the same time to avoid false negatives.

Gastroscopy and Biopsy: The definitive diagnosis of coeliac disease requires a characteristic appearance on histology and at least three biopsies should be taken from the second and third part of the duodenum as the changes due to coeliac disease may be patchy. Histological finding includes villous atrophy, crypt hyperplasia and increased number of intraepithelial lymphocytes in the lamina propria.
The histological pattern seen in coeliac disease is not unique and can be seen in several other clinical situatins including: Giardiasis, Viral gastroenteritis, intestinal lymphoma, Crohn's disease, eosinophilic gastrenteritis, HIV enteropathy and tropical sprue.

If the diagnosis is still uncertain even after biopsy, it is worthwhile checking HLA DQ2 and DQ8.

Ancillary laboratory tests: once coeliac disease is diagnosed, metabolic consequences should be looked for

• Full blood count
• Liver function test
• Iron, B12 and folate
• Calcium, phosphate and Vitamin D level
• TFT
• Blood sugar level
• Bone mineral density measurement

Vertigo

It is the sensation of spinning or swaying while the body is actually stationary with respect to the surroundings. The effects of vertigo may be slight. It can cause nausea and vomiting and, in severe cases, it may give rise to difficulties with standing and walking.

The first task of the examining physician is to determine whether the vertigo is of central or peripheral origin.

The differentiation can be made at the bedside on the basis of

• the type of the spontaneous nystagmus
• head-thrust test
• the severity of imbalance
• the presence or absence of associated neurologic signs.

Type of Nystagmus
Nystagmus of peripheral origin is typically horizontal with a torsional ( rotational ) component. While those of central origin is often purely horizontal, vertical or torsional and usually changes direction with changes in the position of the gaze.

Severity of Imbalance
Patients with an acute peripheral vestibular lesion typically can stand, although they will veer toward the side of the lesion. By contrast, patients with vertigo of central origin are often unable to stand without support.

Head-Thrust Test
It is performed by grasping the patient's head and applying a brief, small amplitude, high acceleration head turn, first to one side and then to the other while the patient fixates on the examiner's nose.
If the catch-up saccades occur after the head thrusts in one direction but no after those in the other direction, this indicates the presence of a peripheral vestibular lesion on that side ( in the labyrinth or the 8th nerve including the root's entry zone in the brain stem )
Watch:
http://www.youtube.com/watch?v=j_R0LcPnZ_w&feature=related
http://www.youtube.com/watch?v=TqTtH1leYyk
A positive head thrust test can occur with brain stem infarction involving the entry zone of the root of the 8th nerve, but invariably, there will be other associated signs of the lateral brain stem (e.g., Horner's syndrome, facial numbness and weakness, hemiataxia and dysarthria )

Presence or Absence of associated neurologic sign
Associated neurological signs such as dysarthria, incoordination, numbness, or weakness suggest a central origin.

Syncope

Syncope is a symptom, defined as a transient, self-limited loss of consciousness, usually leading to falling. The onset of syncope is relatively rapid, and the subsequent recovery is spontaneous, complete, and usually prompt. The underlying mechanism is a transient global cerebral
hypoperfusion.

Presyncope or ‘near-syncope’ refers to a condition in which patients feel as though syncope is imminent.

Non-syncopal conditions: Several disorders resemble syncope in two different ways. In some, consciousness is impaired or lost because of metabolic disorders (including hypoxia, hyperventilation, hypoglycaemia), epilepsy and intoxications. In several other disorders, consciousness is only apparently lost; this is the case in somatization disorders, cataplexy
and drop attacks.

Causes of syncope:

Neurally mediated ( reflex )

• Vasovagal syncope
  
• Carotid sinus hypersensitivity
• Situational syncope

Orthostatic Hypotension

• autonomic failure
• drug and alcohol induced
• volume depletion

Cardiac Arrhythmia

• Implanted device malfunction
• Sinus nodal dysfunction
• Atrioventricular conduction system disease
• Drug induced proarrhythmias
• Paroxysmal SVT and VT
• Inherited syndrome ( e.g., Brugada's syndrome, long QT syndrome )

Structural cardiac or cardiopulmonary disease

• Obstructive cardiac valvular disease
• Obstructive cardiomyopathy
• Myocardial infarction
• Atrial myxoma
• Acute aortic dissection
• Pericardial disease/tamponade
• Pulmonary embolism/pulmonary hypertension

Cerebrovascular

• vascular steal syndrome

Three key questions should be addressed during the initial evaluation:

• Is loss of consciousness attributable to syncope or not?
• Are there important clinical features in the history that suggest the diagnosis?
• Is heart disease present or absent?

Is loss of consciousness attributable to syncope or not?
Differentiating true syncope from other ‘non-syncopal’ conditions associated with real or apparent transient loss of consciousness is generally the first diagnostic challenge and influences the subsequent diagnostic strategy.

Are there important clinical features in the history that suggest the diagnosis?

PMH/o:

• Family history of sudden death, congenital arrhythmogenic heart disease or fainting
• Previous cardiac disease
• Neurological history (Parkinsonism, epilepsy, narcolepsy)
• Metabolic disorders (diabetes, etc.)
• Medication (antihypertensive, antianginal, antidepressant agent, antiarrhythmic, diuretics and QT prolonging agents

Pre-syncopal events:

• Position (supine, sitting or standing)
• Activity (rest, change in posture, during or after exercise, during or immediately after urination, defaecation, cough or swallowing);
• Predisposing factors (e.g. crowded or warm places, prolonged standing, post-prandial period) and of precipitating events (e.g. fear, intense pain, neck movements);
• Nausea, vomiting, abdominal discomfort, feeling of cold, sweating, aura, pain in neck or shoulders, blurred vision;
  

During syncope:

• Way of falling (slumping or keeling over),
  
• skin colour (pallor, cyanosis),
  
• duration of loss of consciousness, breathing pattern (snoring),
  
• movements (tonic, clonic, tonic-clonic or minimal myoclonus, automatism)

Post syncope:

• Autonomous symptoms - Nausea, vomiting, sweating
• confusion
• chest pain, palpitations
• urinary or faecal incontinence

Is heart disease present or absent?
The absence of suspected or certain heart disease excludes a cardiac cause of syncope with the exception of syncope accompanied by palpitations which could be due to paroxysmal tachycardia.

Conversely, the presence of heart disease at the initial evaluation is a strong predictor of cardiac cause of syncope and virtually includes all cardiac syncopes, but its specificity is low as about half of patients with heart disease have a non-cardiac cause of syncope.

Specificity increases in some situations. These are:

• In the presence of heart disease, some historical variables such as blurred vision, syncope occurring in the supine position or during effort, or convulsive syncope suggest a cardiac cause of syncope with high specificity. These patients should probably be hospitalized and cardiological examinations should be given priority.
• Even in the presence of heart disease, a long duration (>4 years) of symptoms, syncope preceeded by abdominal discomfort or followed by nausea and sweating suggest a neurally mediated cause of syncope with high specificity. In these cases autonomic tests should be given priority and, in case of their positivity, a neurally-mediated mechanism is likely and the diagnostic work-up should be stopped.

Further Reading: http://www.escardio.org/guidelines-surveys/esc-guidelines/Documents/SYNCOP/guidelines-syncope-ES-2001.pdf

Oxygenation and mechanisms of hypoxemia

Hypoxemia refers to insufficient oxygenation. It can be caused by 5 mechanisms: hypoventilation, ventilation-perfusion mismatch, right-to-left shunt, diffusion impairment, or reduced inspired oxygen tension.

Hypoventilation — Both arterial (PaCO2) and alveolar (PACO2) carbon dioxide tension increase during hypoventilation, which causes the alveolar oxygen tension (PAO2) to decrease. As a result, diffusion of oxygen from the alveolus to the pulmonary capillary declines. The net effect is hypoxemia.

Hypoxemia due to pure hypoventilation can be identified by two characteristics. First, it readily corrects with a small increase if the fraction of inspired oxygen (FiO2). Second, the A-a gradient is usually normal. An exception exists when the hypoventilation is prolonged because atelectasis can occur, which will increase the A-a gradient. Abnormalities that cause pure hypoventilation include:

• CNS depression, such as drug overdose, structural CNS lesions, or ischemic CNS lesions that impact the respiratory center
• Obesity hypoventilation (Pickwickian) syndrome
• Impaired neural conduction, such as amyotrophic lateral sclerosis, Guillain-Barré syndrome, high cervical spine injury, phrenic nerve paralysis, or aminoglycoside blockade
• Muscular weakness, such as myasthenia gravis, idiopathic diaphragmatic paralysis, polymyositis, muscular dystrophy, or severe hypothyroidism
• Poor chest wall elasticity, such as a flail chest or kyphoscoliosis

V/Q mismatch — Ventilation-perfusion (V/Q) mismatch refers to an imbalance of blood flow and ventilation. It causes the composition of alveolar gas to vary among lung regions:

• Lung regions with low ventilation compared to perfusion will have a low alveolar oxygen content and high CO2 content
• Lung regions with high ventilation compared to perfusion will have a low CO2 content and high oxygen content

In the normal lung, there is V/Q mismatch because both perfusion and ventilation are heterogeneous. Specifically, perfusion is greater in basilar than apical regions, while ventilation is greater in apical than basilar regions. V/Q mismatch is responsible for the normal A-a gradient.

In the diseased lung, V/Q mismatch increases because heterogeneity of both ventilation and perfusion worsen. The net effect is hypoxemia. Hypoxemia due to V/Q mismatch can be corrected with low to moderate flow supplemental oxygen and is characterized by an increased A-a gradient. Common causes of hypoxemia due to V/Q mismatch include obstructive lung diseases, pulmonary vascular diseases, and interstitial diseases.

Right-to-left shunt — A right-to-left shunt exists when blood passes from the right to the left side of the heart without being oxygenated. There are two types of right-to-left shunts:

• Anatomic shunts exist when the alveoli are bypassed. Examples include intracardiac shunts, pulmonary arteriovenous malformations (AVMs), and hepatopulmonary syndrome.
• Physiologic shunts exist when non-ventilated alveoli are perfused. Examples include atelectasis and diseases with alveolar filling (eg, pneumonia, acute respiratory distress syndrome).

Right-to-left shunts cause extreme V/Q mismatch, with a V/Q ratio of zero in some lung regions. The net effect is hypoxemia, which is difficult to correct with supplemental oxygen.

The degree of shunt can be quantified from the shunt equation:

Qs/Qt = (CcO2 - CaO2) ÷ (CcO2 - CvO2)

where Qs/Qt is the shunt fraction, CcO2 is the end-capillary oxygen content, CaO2 is the arterial oxygen content, and CvO2 is the mixed venous oxygen content. CaO2 and CvO2 are calculated from arterial and mixed venous blood gas measurements, respectively. CcO2 is estimated from the PAO2.

Diffusion limitation — Diffusion limitation exists when the movement of oxygen from the alveolus to the pulmonary capillary is impaired. It is usually a consequence of alveolar and/or interstitial inflammation and fibrosis, such as that due to interstitial lung disease. In such diseases, diffusion limitation usually coexists with V/Q mismatch, which makes the relative contribution of each to the patient's hypoxemia uncertain.

Diffusion limitation is characterized exercise-induced or -exacerbated hypoxemia. This is illustrated by the following:

• During rest, blood traverses the lung relatively slowly. Thus, there is usually sufficient time for oxygenation to occur even if diffusion limitation exists.
• During exercise, cardiac output increases and blood traverses the lung more quickly. As a result, there is less time for oxygenation.

• - In the healthy individuals, several compensatory mechanisms occur. Pulmonary capillaries dilate, which increases the surface area available for gas exchange by perfusing additional regions of lung. PAO2 also increases, which promotes oxygen diffusion by increasing the oxygen gradient from the alveolus to the artery. The net effect is that full oxygenation is sustained.
• - In patients with diffusion limitation, there is insufficient time for oxygenation to occur. In addition, most such patients have parenchymal destruction, which renders it impossible to recruit additional surface area for gas exchange. The net effect is measurable hypoxemia.

Reduced inspired oxygen tension — The inspired oxygen tension (PiO2) is a component of the alveolar gas equation that was described above. It can be determined by the equation:

PiO2 = FiO2 x (Patm - PH2O)

where FiO2 is the fraction of inspired oxygen (0.21 at room air), Patm is the atmospheric pressure (760 mmHg at sea level), and PH2O is the partial pressure of water (47 mmHg at 37 degrees C).

Reduction of the PiO2 will decrease the PAO2. This impairs oxygen diffusion by decreasing the oxygen gradient from the alveolus to the artery. The net effect is hypoxemia. A reduced PiO2 is most commonly associated with high altitude.

Headache

Classification:

• The Primary Headache.
• The Secondary Headache.
• Cranial Neuralgia, Central and primary facial pain and other headaches.

Primary headaches include migraine, cluster headache and tension headache.

Secondary headaches can be divided into intracranial and extracranial causes.
Intracranial:
Raised intracranial pressure
Vascular - Cerebral infarct, intracerebral haemorrhage, subarrhanoid haemorrhage, subdural haemorrhage and extradural haemorrhage.
Non-vascular - Abscess, Meningitis, Encephalitis, Tumor, benign intracranial hypertension and congenital lesion.
Reduced intracranial pressure - lumbar puncture, CSF leakage following head injury.

Extracranial: can be subdivided into local and systemic causes.
Local - examples includes refractive errors of eyes, glaucoma, sinusitis, dental disorder and cervical spondylosis, etc.,.
Systemic - carbon dioxide retention, hypoglycemia, Depression, Fever.

The aim of this blog is about medically important headaches which must not be missed.
1) Thunderclap headache
2) Intracranial infection especially encephalitis

Thunderclap headache
Thunderclap headache refers to a severe and explosive headache with peak intensity at onset. Diagnostic criteria includes:
1) very severe pain intensity
2) Instantaneous or hyperacute onset of pain ( less than 30 seconds )

Thunderclap headache is a clinical emergency which mandates a swift evaluation with investigations aimed at excluding a subarachnoid haemorrhage.

The differentials diagnosis for thunderclap headache include:

• Subarachnoid haemorrhage
• Cerebral Venous Sinus Thrombosis
• Cervicocephalic arterial dissection
• Acute hypertensive crisis
• Spontaneous intracranial hypotension
• Pituitary apoplexy
• Benign thunderclap headache
  

These disorders with the exception of subarachnoid haemorrhage may often evade detection by CT and lumbar puncture.

Cerebral Venous Sinus Thrombosis

75% of CVST present with headache which is often persistent, worse upon recumbancy and aggravated by the valsalva manoeuvre. 40 % of CVST patients may have raised intracranial pressure without alteration of CSF cytochemistry studies.

When there is clinical suspicion of CVST, CT has now been supplanted by MRI, which should now be initial investigation.

Cervicocephalic arterial dissection
Unilateral headache, especially in the anterior head region is strongly suggestive of internal carotid artery dissection. There can be delayed focal cerebral ischaemic events.
MR angiography is fast becoming the imagin modlity of choice in demonstrating the arterial dissection.

Pituitary Apoplexy
It is characterised by acute headache, ophthalmoplegia, diminished visual acuity and altered mental status caused by the sudden infarctionor haemorrhage of a pituitary gland.

Benign ( idiopathic ) thunderclap headache
It is a diagnosis of exclusion and so, in the absence of organic intranial pathology, thunderclap headache may occur as a benign and potentially recurrent idiopathic headache disorder.

Diagnostic Evaluation of thunderclap headache:

Brain CT is a must in all patients. The sensitivity of subarachnoid haemorrhage is 98 % within the first 12 hr of onset of headache and 93 % within the first 24 hours. However, sensitivity decreases to 86% after day 1 and 76 % after day 2.

Lumbar puncture is therefore required in all patients whose initial CT is negative, equivocal or technically inadequate.

In cases where the CSF or clinical findings are difficult to interpret or the index of suspicion is unusually high ( family or personal history of subarachnoid haemorrhage ) MRA is an appropriate procedure.

Viral Encephalitis:

Acute encephalitis constitutes a neurological emergency and it is imperative that appropriate treatment is started as soon as possible.

1. Establishing the diagnosis of encephalitis
Three differentials for acute or subacute causes of confusion includes

1. Infective encephalitis
2. Acute disseminated encephalomyelitis
3. Encephalopathy/delerium

Acute disseminated encephalomyelitis may be distinguished from infective encephalitis by the younger age of the patient, prodromal history of vaccination or infection, absence of fever at the onset of symptoms and the presence of multiple neurological signs affecting optic nerves, brain, spinal cord and peripheral nerve roots.

Infective encephalitis is suspected in a febrile patients who presents with altered consciousness and the presence of focal neurological signs and focal seizures. However, cerebral malaria is considered to an example of infective encephalopathy rather than encephalitis since the neurological symptoms of cerebral malaria result from brain hypoxemia and metabolic complications ( hypoglycemia and acidosis ) due to heavy parasitaemia leading to capillary occlusion.

2. Establishing the cause of infective encephaltitis

Neuropathies predominant in upper limbs

Neuropathies predominant in upper limbs

• Guillain-Barré syndrome
• Diabetes mellitus
• Porphyria
• Hereditary motor sensory neuropathy
• Vitamin B₁₂ deficiency
• Hereditary amyloid neuropathy type II*
• Lead neuropathy

Neuropathies with cranial nerve involvement

Neuropathies with cranial nerve involvement

• Diabetes mellitus
• Guillain-Barré syndrome
• HIV/AIDS
• Lyme disease
• Diphtheria
• Sarcoidosis Neoplastic invasion of skull base or meninges