Medicine Hack

BPAP - Bilevel Positive Airway Pressure Ventilation

2020-04-30T20:33:00.004+03:00

Bilevel noninvasive ventilation provides:

1) IPAP - inspiratory positive airway pressure and

2) EPAP - expiratory PAP at two different levels.

This is typically delivered with a tight fitting nasal or face mask which allows for the development of positive airway pressure.

The noninvasive therapy should be initiated as early as possible in case of respiratory failure and is best used for short term.

"Delta PAP" is the difference between IPAP and EPAP. It directly correlates with the tidal volume delivered. If the "delta PAP" is larger then the tidal volume will be larger and hence it will provide a better alveolar ventilation.

INITIAL SETTINGS

It is quite safe to start the following initial settings:

1) EPAP 3 to 5 cm H2O (2 - 4 mm Hg) – It can be increased to around 10 cm H2O if ever the oxygenation remains inadequate tidal volume.

2) IPAP 8 to 12 cm H2O (6 - 9 mm Hg) – This can be increased in increments of 2 cm H2O as tolerated by the patient, to a maximum of 20 cm H2O. Up titration will depend on the degree of dyspnea, respiratory rate and patient-ventilator synchrony.

3) Bilevel NIV (BPAP) mode - The spontaneous/timed (S/T) setting with a backup rate of 8 to 12 breaths/minute is the preferred mode since it ensures that all breaths are supported and that a minimum respiratory rate is provided if the patient hypoventilates.

Emphysematous pyelonephritis - Review

2017-04-15T11:54:00.002+03:00

DEFINITION
Emphysematous pyelonephritis is an acute necrotizing infection characterized by gas formation.
It is characterized by the presence of gas in and around the kidney.

ETIOLOGY
E. coli (58%) and K. pneumoniae (21%) are the organisms most commonly isolated. Clostridium and Enterobacter spp may also be responsible, 7% each.

RISK FACTORS
1) Diabetes mellitus (70-90%)- usually patients with poor glucose control. High levels of glucose in the urine serve as a substrate for these bacteria and large amounts of gas are generated through natural fermentation
2) Obstruction (25-40%)- it is another common predisposing factor for emphysematous pyelonephritis.

For non-diabetics, protein fermentation is a proposed source of gas formation.

CLINICAL FEATURES
7% of cases may be asymptomatic.
If symptomatic, patients may complain of pneumaturia, irritative lower tract voiding symptoms, flank pain or may present in a severe septic condition with an acute abdomen and high grade fever.

DIAGNOSIS
1) Plain radiograph of the abdomen can help us in 80-85 % of cases.
2) CT is considered the optimal imaging technique for confirming emphysematous infection and characterizing the extent of involvement.

According to radiological findings and CT scans, emphysematous pyelonephritis can be classified as follows:
Class 1— gas confined to the collecting system
Class 2— gas confined to the renal parenchyma alone
Class 3A— perinephric extension of gas or abscess
Class 3B— extension of gas beyond the Gerota fascia
Class 4— bilateral EPN or EPN in a solitary kidney

Plain abdominal radiograph showing presence of air around the left kidney

CT scan showing left emphysematous pyelonephritis with presence of gas and parenchymal destruction

CT scan of a diabetic patient with emphysematous pyelonephritis due to uncontrolled diabetes and renal stones.

MANAGEMENT
1) Medical management includes antimicrobial therapy, bladder drainage and glycemic control. effective.
2) Surgical intervention usually is required for only 10% of the cases. Emergency nephrectomy was traditionally considered necessary but currently, percutaneous drainage is the recommended initial approach.

Later, elective nephrectomy may be required for some patients.

First published on: 15 April 2017

Torsades de pointes - twisting of the points

2017-03-31T10:55:00.001+03:00

DEFINITION
Torsades de pointes is a polymorphic ventricular tachycardia that occurs frequently in cases of QT interval prolongation.

This can be due to congenital or acquired Long QT interval syndrome.

It is characterized by a progressive change of the electrical axis, typically rotating 180 degrees in approximately 10 to 12 cycles and the amplitude, as though the depolarization and repolarization of the ventricle was turning on a point.

This results in the characteristic sinusoidal twisting of the peaks of the QRS complexes around the isoelectric line of the recording.

EKG

The tachycardia rate typically is in the range of 150 to 300 beats/min.

It is usually a self-limiting arrhythmia that spontaneously dies out after a few tens of cycles and only in a minority of cases that it degenerates into ventricular fibrillation and can lead to sudden cardiac death.

Drugs that can prolong the QT interval and induce Torsades de pointes are:

It can also be caused by electrolyte imbalances like, hypokalemia, hypomagnesemia and less commonly hypocalcemia.

First published on: 31 March 2017

Endomysium, Perimysium and epimysium - definition, histology

2016-12-27T12:54:00.000+02:00

Each muscle fibre is closely surrounded by connective tissue.
This acts as a support for the muscle fibres and unites them to each other.

1) Each muscle fibres is surrounded by delicate connective tissue that is called the endomysium.
2) Individual fasciculi are enclosed by a stronger sheath of connective tissue called the perimysium.
3) The entire muscle is surrounded by connective tissue called the epimysium.

This is illustrated by the schematic diagram below.

1= perimysium, 2= endomysium, 3= fasciculus.

At the junction of a muscle with a tendon, the fibres of the endomysium, the perimysium and the epimysium become continuous with the fibres of the tendon.

First published on: 27 December 2016

Chronic sinusitis - Steam inhalation not effective, nasal irrigation may help

2016-07-24T22:38:00.000+03:00

DEFINITION
Chronic sinusitis refers to inflammation the paranasal sinuses for a period of at least 12 weeks. The most important cause of chronic sinusitis is failure of acute infections to resolve.

PATHOPHYSIOLOGY
Acute infection destroys the normal ciliated epithelium, thus impairing drainage from the sinuses. There is pooling and stagnation of secretions in the sinuses which favours infections. Persistence of infection causes mucosal changes, such as loss of cilia, edema and polyp formation. We eventually have a vicious cycle.

CLINICAL FEATURES
Patients may complain of blocked nose, runny nose, headache and a reduced sense of smell (hyposmia). Foul-smelling discharge suggests anaerobic infection. Some people will also have nasal polyps.

TREATMENT
1) We should always search for underlying aetiological factors which obstruct sinus drainage and ventilation.
2) A work-up for nasal allergy may be required.
3) Culture and sensitivity of sinus discharge helps in the proper selection of an antibiotic.

Initial treatment of chronic sinusitis is conservative, including antibiotics, decongestants, antihistaminics and sinus/nasal irrigations.

Nasal irrigation is a procedure that rinses the nasal cavity with isotonic or hypertonic saline solutions. The patient instils saline into one nostril and allows it to drain out of the other nostril, bathing the nasal cavity.

In this Cochrane review, even though the level of evidence was low, the authors concluded that:

There is some benefit of daily, large-volume (150 ml) saline irrigation with a hypertonic solution when compared with placebo.

A recent article published in the Canadian Medical Association Journal, concluded that steam inhalation was not effective but nasal irrigation may provide some symptomatic relief especially with regard to headaches.

First published on: 24 July 2016

The common cold - definition, diagnosis and treatment

2016-06-10T01:04:00.000+03:00

DEFINITION
It is an upper respiratory tract illness that comprises of rhinorrhea and nasal obstruction as the main symptoms.

EPIDEMIOLOGY
5- 7 times/ year in children and 2-3 times/ year in adults.
most commonly seen between the early fall and late spring in temperate climates.
Transmission of the virus may occur via direct contact, large-particle aerosol, or small-particle aerosol.

MICROBIOLOGY
The rhinoviruses are usually responsible for the majority of cases. Coronavirus, respiratory syncytial virus and metapneumovirus may also be associated with the common cold syndrome.

DIAGNOSIS
The diagnosis of the common cold is a clinical diagnosis. Polymerase chain reaction assay can determine the responsible pathogen but this is rarely useful in the management of the patient.

THERAPY
Management is mainly directed towards the bothersome symptoms as no specific antiviral agents are useful in the treatment.

First published on: 10 June 2016

Reading chest radiograph - Penetration

2016-01-02T00:47:00.002+02:00

PENETRATION

Penetration is one of the five technical factors that help you in determining whether a radiograph is technically adequate.

ADEQUATE PENETRATION

If a frontal chest radiograph is adequately penetrated, you should be able to see the thoracic spine through the heart shadow.

In the radiograph above, we can see the thoracic spine through the heart shadow (solid white line).

UNDER PENETRATION

It means that the penetration is inadequate. The radiograph will appear as too white. We will not be able to see the thoracic spine through the heart. This can lead us into making interpretation errors.
1) The pulmonary markings may appear more prominent and these can be mistaken for being due to a congestive heart failure or pulmonary fibrosis.
2) The left lung base will appear opaque thus obscuring the left hemidiaphragm. This can mimic or hide a true disease in the left lower lung field e.g. left lower lobe pneumonia or left pleural effusion.

To avoid these misinterpretations always correlate clinically. Also if you are suspecting a congestive heart failure, look for other signs apart from increased pulmonary markings e.g. effusions, Kerley lines etc. A lateral radiograph will also help us when faced with these dilemmas.

In this frontal chest radiograph we can see that there is under penetration.

The solid black line shows that the thoracic spine cannot be seen through the heart shadow.

The broken black lines show that the left hemidiaphragm is not clearly visible.

OVER PENETRATION
In this case, the lung markings will appear decreased or absent. The patient may be mistaken of having a pneumothorax or emphysema. We may also miss a pulmonary nodule if the radiograph is too dark.

This is an example of an over penetrated chest radiograph.

At first glance we may suspect emphysema in this patient because of the increased lucency at the apices but when we look at the diaphragm we find that it is not flattened, which means there is no hyperinflation as expected for a case of emphysema.

First published on: 01 January 2016

BMI versus waist to hip ratio

2015-11-30T12:10:00.000+02:00

DEFINITION
Obesity is a state of excess adipose tissue mass. It is often viewed as equivalent to an increased body weight. This is not true because muscular individuals may have increased body weight but are not obese.

Weight follows a continuous distribution pattern in human population. The point at which mortality and morbidity becomes statistically significant is the cut-off to call a patient obese.

METHODS
Various methods have been used to measure obesity. These include:
1) Anthropometry (skin-fold thickness)
2) Densitometry (underwater weighing)
3) CT/MRI
4) Electrical impedance.

Still the most common techniques used in clinical practice are:
1) BMI measurement
2) Waist-to-hip ratio measurement.

BMI
It is not an accurate measure of obesity but since it is simple to calculate, it is the most frequently measured parameter.

At similar BMI, women usually have more fat than men. When the BMI > 25 Kg/m2, morbidity starts to increase and if associated with risk factors then therapeutic interventions should be considered.

WAIST-TO-HIP RATIO (WHR)
Intra-abdominal or abdominal subcutaneous tissue fat has more significant implications on morbidity than fat present in the buttocks and lower extremities. A WHR > 0.9 for women and > 1.0 for men is considered abnormal. (0.85 and 0.90 respectively according to WHO)

Insulin resitance, hypertension, dyslipidemia and diabetes mellitus are more strongly associated with intra-abdominal / abdominal subcutaneous tissue fat than to overall adiposity.

The probable explanation of this issue is that intra-abdominal adipocytes may be lipolytically more active than those from other depots. There is also release of free fatty acids into the portal circulation and this has adverse metabolic effects, especially on the liver.

A recent article published in the Annals of Internal Medicine concluded that
" normal-weight U.S. adults with central obesity have the worst long-term survival compared with participants with normal fat distribution, regardless of BMI category, even after adjustment for potential mediators. "

First published on: 30 November 2015

Alcoholic liver disease

2015-09-22T21:54:00.001+03:00

INTRODUCTION
Chronic and excessive use of alcohol is one of the major causes of liver disease.

90% of daily heavy drinkers (>60 g alcohol/day) as well as binge drinkers have fatty liver but a smaller percentage (10-35%) of drinkers progress to alcoholic hepatitis which is a precursor for cirrhosis.

The long-term risk is 9 times higher in patients with alcoholic hepatitis compared to those with fatty liver alone.

Some population-based surveys have documented that men must drink 40 to 80 g of alcohol daily and women must drink 20 to 40 g daily for 10 to 12 years to achieve a significant risk of liver disease.

Liver pathology consists of 3 major lesions that are progressive and rarely exist in a pure form:
1) fatty liver (usually reverses quickly with abstinence),
2) alcoholic hepatitis and
3) cirrhosis.

Prognosis of severe alcoholic liver disease (ALD) is bad. Mortality of patients with alcoholic hepatitis concurrent with cirrhosis id nearly 60% at 4 years.

Although alcohol is a direct hepatotoxin, it is unclear why only 10-20% of alcoholics will develop alcoholic hepatitis. It appears to involve a complex interaction of facilitating factors like drinking patterns, diet, obesity and gender.

EPIDEMIOLOGY
Harmful use of alcohol results in 2.5 million deaths each yr. Most of the mortality is due to cirrhosis. The mortality is declining now because of decreased consumption of alcohol in the Western countries except in the U.K, Romania, Russia and Hungary.

ETIOLOGY
a) Quantity and duration of alcohol intake - are the most important risk factors. Time taken to develop liver disease is directly related to the amount of alcohol consumed.
b) There is no clear role of the type of beverage and the pattern of drinking.
c) Genetic - some people are genetically predisposed for alcoholism and subsequently to the ill effects of alcohol on the liver.
d) Gender - It is a strong determinant for ALD. Women are more susceptible to alcoholic liver injury. They develop advanced liver disease with substantially less alcohol intake. Gender-dependent differences may be due to the effects of estrogen, proportion of body fat and gastric metabolism of alcohol.
e) Chronic infection with Hepatitis C virus - It is an important comorbidity in the progression of ALD to cirrhosis in chronic and excessive drinkers. Even moderate alcohol intake of 20-50 g/day increases the risk of cirrhosis and hepatocellular cancer. Intake of more than 50 g/day decreases the efficacy of interferon-based antiviral therapy.

PATHOGENESIS
It is unclear but what is known is that alcohol can act as a direct hepatotxin and malnutrition does not play a major role.
- Alcohol is metabolised to acetyldehyde which in turn initiates an inflammatory cascade that results in a variety of metabolic responses.
- Steatosis from lipogenesis, fatty acid synthesis and depression of fatty acid oxidation occur secondary to effects on sterol regulatory transcription factor (SRTF) and peroxisome proliferator-activated receptor alpha (PPAR-alpha).
- Intestinal derived endotoxin initiates a pathogenic process through toll-like receptor-4 and TNF-alpha. This facilitates hepatocyte apoptosis and necrosis.
- Cell-injury endotoxin also activates innate and adaptive immunity pathways. There is release of pro-inflammatory cytokines (TNF-alpha) and proliferation of T/B cells.
- Production of toxic protein-aldehyde adducts, generation of reducing equivalents and oxidative stress also contribute to liver injury.

Finally hepatocyte injury and impaired regeneration are associated with stellate cell activation and collagen production which are key events in fibrogenesis. The resulting fibrosis causes architectural derangement of the liver and the associated pathophysiology.

PATHOLOGY
Fatty liver is the initial and most common histologic response to hepatotoxic stimuli, including excess alcohol ingestion. Accumulation of fat within the perivenular hepatocytes coincides with the location of alcohol dehydrogenase. Continuing alcohol ingestion results in deposition of fat throughout the entire hepatic lobule.

Alcoholic fatty liver - traditionally regarded as benign but appearance of steatohepatitis and certain features like giant mitochondria, perivenular fibrosis and microvesicular fat are associated with progressive liver injury.

Hallmarks of alcoholic hepatitis include: (hepatocyte injury)
a) ballooning degeneration,
b) spotty necrosis,
c) polymorphonuclear infiltrate and
d) fibrosis in the perivenular and perisinusoidal space of Disse.

Mallory-Denk bodies are often present in florid cases but these are neither specific nor necessary to establish the diagnosis.

CLINICAL FEATURES
Usually the patients are asymptomatic.
Hepatomegaly is often the only clinical finding.
It is very important to assess the drinking history and estimate how much alcohol is consumed per day and for how long.
1 beer, 4-5 ounces of wine, 1.5 oz of 40% liquor and 1 ounce (approximately 30 mL) of 80% spirits all have around 12 g of alcohol.

- Patients with fatty liver may have:
1) right upper quadrant discomfort,
2) nausea and
3) rarely jaundice.

- Patients with alcoholic hepatitis may have:
1) fever
2) spider nevi
3) jaundice
4) abdominal pain.
We can also see portal hypertension, ascites and variceal bleeding even in the absence of cirrhosis.

LABORATORY FINDINGS
These are most identified through routine screening tests.

Fatty liver - laboratory abnormalities are non-specific
Modest elevation of AST, ALT, GGTP are seen. Triglycerides and bilirubin may also be increased.

Alcoholic hepatitis
a) increased AST and ALT - by 2-7 fold but rarely greater than 400 IU.
b) AST/ALT ratio greater than 1.
c) hyperbilirubinemia
d) modest increase in alkaline phosphatase

If synthetic function is deranged then the condition is more serious. Hypoalbuminemia and coagulopathy are more common in advanced liver disease.

Ultrasonography is also a useful investigation as it can determine the size of the liver and detect any fatty infiltration. If it demonstrates portal vein flow reversal, ascites and intraabdominal venous collaterals then the condition has less potential for complete reversal.

Below is an ultrasonographic picture of hepatic steatosis. Fatty infiltration produces an increased reflectivity of hepatic parenchyma, known as ‘bright liver pattern’. This feature can be assessed by comparing liver parenchyma with the right kidney’s cortex, which normally presents an echogenicity equal to or slightly lower than that of the liver. Severe steatosis produces a strong attenuation in the deepest liver sections, resulting in poor explorability.

PROGNOSIS
Critically ill patients with alcoholic hepatatis have short term (30-day) mortality rates exceeding 50%.
A Discriminant Function (DF) above 32 and a Model for End-stage Liver Disease (MELD) greater than 21 is associated with poor prognosis.
Worse prognosis if there is associated:
a) ascites,
b) variceal hemorrhage,
c) deep encephalopathy and
d) hepatorenal syndrome.

TREATMENT
a) Complete abstinence from alcohol is the mainstay for treatment.
b) Patients with severe alcoholic hepatitis i.e. DF>32 and MELD>21 should be given Prednisone 40mg/day or Prednisolone 32mg/day for 4 weeks followed by tapering over 4 weeks.
c) Alternatively Pentoxifylline, a non-specific TNF inhibitor, can be used in a dosage of 400mg 3 times per day for 4 weeks.
d) Liver transplantation is an accepted indication for treatment in selected and motivated patients with end-stage cirrhosis.

Below is an algorithm showing how to manage alcoholic hepatitis:

N.B Monoclonal antibodies that neutralize serum TNF-alpha should not be used as studies have reported an increase in the number of deaths secondary to infections and renal failure.

First published on: 23 September 2015

Voltaire - Medical quote no longer valid

2015-09-02T13:09:00.000+03:00

Times have changed Monsieur Voltaire.

Your quote is no longer valid in our "Evidence Based Medicine" world.

The quote's accuracy is stunning though if applied to quacks.

Our advice to young practitioners : DO NOT BLINDLY FOLLOW WHAT A SENIOR DOCTOR IS DOING.
Try to understand why he did something for that specific problem.

Always ask if you do not understand.

Article resources:
1) "Voltaire lisant L’année littéraire de Fréron", huile sur toile de Jacques Augustin Catherine Pajou, 1811

Last reviewed on: 2 September 2015

Menopause - Definition, symptoms and hormone replacement therapy

2015-07-19T13:04:00.000+03:00

Menopause refers to a point in time that follows 1 year after the permanent cessation of menstrual periods that occurs naturally or is induced by surgery, chemotherapy or radiation.

On average, natural menopause occurs between 50 and 51 years (range 45–59) and is part of the process of normal ageing. It has been noted that smoking advances the age of menopause by approximately 2 years.
The diagnosis can only be made retrospectively and it is usually preceded by months or years of irregular cycles, that is not associated with some other physiological or pathological causes.

If the cessation of menses occurs before the age of 40, then it is referred to as the "Premature ovarian failure".
The older terms perimenopause or climacteric generally refer to the time period in the late reproductive years, usually late 40s to early 50s. Characteristically, it begins with menstrual cycle irregularity and extends to 1 year after permanent cessation of menses. The more correct terminology for this time is menopausal transition. This transition typically develops over a span of 4 to 7 years, and the average age at its onset is 47 years

Up to 75% of women will experience adverse symptoms related to menopausal transition while the others may not have any symptoms at all. Although symptoms associated with menopause occur as a result of oestrogen deficiency, replacing it is not always the treatment of choice.
The use of HT should be made on an individual basis, after careful consideration of quality of life and personal risk factors. In addition to any pharmacological treatments considered, lifestyle modifications are essential.

Below a few of the symptoms are discussed and whether hormone replacement may be helpful:

Hot flushes are characterised by a feeling of intense warmth, often accompanied by profuse sweating, anxiety, skin reddening and palpitations. They are sometimes followed by chills.
In most cases, they will resolve in around 1 year or less without any treatment.
1/3 rd of the patients will have symptoms for up to 5 years after natural menopause and in 20% they may persist for up to 15 years or more.
Menopause induced by surgery is associated with about a 90% probability of hot flushes during the first year. In these cases, symptoms are often more abrupt and severe and can last longer than those associated with a non-surgical menopause.

Hormone therapy is the most effective (80% efficacy) treatment for vasomotor symptoms associated with menopause at any age, but benefits are more likely to outweigh risks for symptomatic women before the age of 60 years or within 10 years after menopause.
Extra care must be taken in women with a history of hormone-dependent cancer, e.g. breast cancer.

Genitourinary symptoms due to menopause can affect up to 50% of women, however it is under diagnosed and under treated. The pathology here is that there is a loss of estrogen which results in urogenital ageing. The tissues of the vaginal walls becomes thinner since the amount of collagen and elastin is reduced. The walls become pale, thin and lose their elasticity. A reduction in vaginal secretions and decreased tissue elasticity also increases the susceptibility to trauma and pain or irritation during or after intercourse.

In addition to vulvo-vaginal symptoms, the less acid pH of the estrogen-deficient vagina increases the likelihood of urinary tract infections.

Vaginal symptoms become apparent 4–5 years after the menopause. 25–50% of all postmenopausal women have some objective changes as well as subjective complaints.
Symptoms may include vaginal dryness (75%), dyspareunia (38%), vaginal itching, burning and pain (15%).
Locally administered vaginal estrogens (creams, pessaries, tablets and vaginal rings) are equally effective in the treatment of menopause-related vulval and vaginal symptoms. Local estrogen therapy will lower vaginal pH, thicken the epithelium, increase blood flow and improve vaginal lubrication.

There are no evidence to support the use of hormone replacement for the urinary symptoms.

The decline in estrogen results in a decrease in the bone mineral density and a subsequent significant increase in the prevalence of osteoporosis.

General management includes:
1) assessment of the risk of falls and their prevention,
2) maintenance of mobility and
3) correction of nutritional deficiencies, particularly of calcium, vitamin D and protein.

Pharmacological interventions include bisphosphonates, denosumab, parathyroid hormone peptides, raloxifene and strontium ranelate. All have been shown to reduce the risk of vertebral fracture and some have been shown to reduce the risk of non-vertebral fractures. However, all are associated
with side effects and many women will fail to comply.
Hormone therapy reduces the risk of spine and hip, as well as other osteoporotic fractures even in women at low risk. It would appear that half of the traditional bone conserving doses are effective in conserving bone mass and are successful means of fracture prevention. However, hormone replacement is not the first line therapy in treating post menopausal osteoporosis.

The incidence of CVD increases with age and menopause may have an adverse effect. Hormone therapy was thought to confer CVD risk reduction but some studies demonstrated an increased number of coronary heart disease events and strokes and concluded that the risks outweighed the benefits. These studies were carried out on elderly women though and probably there was already an element of atherosclerosis that influenced the outcomes. Recent studies suggest that if hormone replacement is started soon after menopause, it may actually be beneficial.

Since the sex hormones are known to be thrombogenic there is an expected increase in the risk of deep vein thrombosis and stroke when using oral replacement therapy. The risk is further increase if the patient is a smoker.

Hyperhomocysteinemia

2015-04-21T00:28:00.001+03:00

Introduction:
Homocysteine is a sulphur containing amino acid that is produced during the conversion of methionine to cysteine.

Hyperhomocysteinemia results when there is an abnormality in the homocysteine metabolism.
It is an independent risk factor for stroke, MI, peripheral arterial disease and venous thrombotic disease.

Even mild to moderate hyperhomocysteinemia is a significant risk factor for vascular disease.

Pathophysiology:

The amino acid homocysteine is normally metabolized via the transsulfuration pathway by the enzyme cystathionine-β-synthase (CBS), which requires vitamin B6 as co-factor and via the
remethylation pathway by the enzymes methylenetetrahydrofolate reductase (MTHFR),
which is folate dependent and methionine synthase, which requires vitamin B12 as co-factor.

1 - Methylenetetrahydrofolate reductase
2 - Methionine synthase

Hyperhomocysteinemia can be either:
1) Inherited or
2) Acquired.

Inherited
Inherited severe hyperhomocysteinemia (plasma level >100 µmol/L), as seen in classic homocystinuria, may result from homozygous MTHFR and CBS deficiencies and more rarely from inherited errors of cobalamin metabolism. Classic symptoms for homozygous patients include premature vascular disease and thrombosis, mental retardation, ectopic lens and skeletal abnormalities.

Inherited mild to moderate hyperhomocysteinemia (plasma level >15 to 100 µmol/L) may result from heterozygous MTHFR and CBS deficiencies, but most commonly results from the thermolabile variant of MTHFR (tlMTHFR) that is encoded by the C677T gene polymorphism. Heterozygous carriers of the tlMTHFR mutation have normal plasma homocysteine levels unless folate levels are
reduced.

Acquired
Acquired hyperhomocysteinemia may be caused by folate deficiency, vitamin B 6 or B 12 deficiency, renal insufficiency, hypothyroidism, type II diabetes mellitus, pernicious anemia, inflammatory bowel disease, advanced age, climacteric state, carcinoma (particularly involving breast, ovaries or pancreas) and acute lymphoblastic leukemia, as well as methotrexate, theophylline and phenytoin therapy.

VTE risk is most closely related to elevated fasting plasma homocysteine levels, regardless of etiology. Hyperhomocysteinemia (plasma level >18.5 µmol/L) has been associated with a two- to fourfold increased VTE risk.

The precise mechanisms underlying the thrombogenicity of homocysteine remain unclear. Several diverse mechanisms have been proposed, including endothelial cell desquamation, low-density lipoprotein (LDL) oxidation, promotion of monocyte adhesion to endothelium and factor V activation and promotion of thrombin generation.
Homocysteine also enhances platelet aggregation and adhesiveness as well as turnover, presumably as a result of endothelial cell injury.

Laboratory Diagnosis:
The initial step in the evaluation of the patient with suspected hyperhomocysteinemia involves measurement of fasting total plasma homocysteine (the sum of nonprotein-bound and proteinbound).
A normal value in the nonfasting setting does not normally require repeating.

Standardized methionine loading test
Testing 2 to 8 hours after an oral methionine load (100 mg/kg) increases the sensitivity of detecting occult vitamin B6 deficiency and obligate heterozygotes for CBS deficiency, but methionine loading is not routinely recommended.
Vitamin B12 and folate deficiency do not affect post-methionine loading homocysteine values.
After 4-6 hours the level of homocysteine is measured again.
A level 5 times that of the fasting one or an increase by 40 µmol/L is considered a positive test for hyperhomocysteinemia.
In patients found to have elevated levels of homocysteine, testing for vitamin B12 deficiency is advocated to avoid missing subclinical deficiency before
beginning oral folic acid therapy.

Treatment:
1) Folic acid supplementation is the mainstay therapy. The usual recommended dose is 0.4 to 1.0 mg daily. This causes a 25% decrease in the homocysteine level.
2) Because patients with subclinical vitamin B12 deficiency may be prone to developing
peripheral neuropathy if they receive folic acid supplementation alone, additional treatment with 0.5 mg/day of oral vitamin B12 has been advocated. An additional 7% reduction of homocysteine levels was noted with vitamin B12 supplementation.
Vitamin B12 administration results in normalization of homocysteine levels in B12-deficient individuals. In these patients, a monthly intramuscular injection of 200 to 1,000 µg of vitamin B12 is considered adequate replacement.
3) Vitamin B6 supplementation did not appear to have any effect on homocysteine levels.
4) Thrombotic events in hyperhomocysteinemic patients should be treated accordingly.

kussmaul breathing pattern - description and causes

2015-03-09T20:58:00.000+02:00

This type of breathing pattern was first described by Adolph Kussmaul, a german physician in 1874. He noticed that his patients with diabetic ketoacidosis had a pattern of breathing which he first labelled as having "air hunger".

In the Kussmaul type of breathing, the patient is breathing heavily i.e hyperventilating along with tachypnea.
So we will find that the amplitude of the breaths along with the rate will be increased.
There is usually no pauses between the breaths.

This is not specific for diabetic ketoacidosis. It can also appear in other types of severe metabolic acidoses e.g alcoholic ketoacidosis .

Adverse effects of Amiodarone

2015-02-15T12:47:00.000+02:00

1) Hypotension can occur especially with the intravenous form due to vasodilation and depressed myocardial performance. Long-term oral therapy can also cause depressed contractility but it is unusual.

2) Nausea can sometimes be seen during the loading phase. All we have to do is to decrease the daily dose of the medication.

3) Pulmonary fibrosis is the most serious adverse effect during chronic amiodarone therapy. The fibrosis can be rapidly progressive and fatal. The risk factors include: underlying lung disease, doses of 400 mg/day or more and recent pulmonary insults such as pneumonia. Early amiodarone toxicity can be detected using pulmonary function tests and serial chest X-rays.

4) Other adverse effects that may be seen during long-term therapy include
a) corneal microdeposits (which often are asymptomatic),
b) hepatic dysfunction,
c) vivid and disturbing dreams
d) neuromuscular symptoms (most commonly peripheral neuropathy or proximal muscle weakness), e) photosensitivity and
f) hypo- or hyperthyroidism.

Aminoglycosides - why -mycin and -micin

2015-02-08T09:33:00.000+02:00

The aminoglycoside group includes gentamicin, amikacin, netilmicin, kanamycin, tobramycin, streptomycin, paromomycin and neomycin.

These drugs have a good action against aerobic gram-negative bacteria.

They are rapidly bactericidal. Bacterial killing is concentration dependent: The higher the concentration, the greater is the rate at which bacteria are killed.

As noted above, some of the names end by -micin while others by -mycin. The reason behind this lies in the origin of the antibiotics.

All the antibiotics ending with -mycin are either natural products or semisynthetic derivatives of compounds produced by a variety of soil actinomycetes notably Streptomyces.
Those ending with -micin are derived from other actinomycetes e.g Micromonospora.

Atrial septal defect device closure

2015-01-24T12:15:00.000+02:00

This procedure is called as Atrial septal defect (ASD) device closure.

Transesophageal echocardiography (TEE) is must before procedure for:
1) actual sizing of the defect
2) defining the rims - to hold device in place
3) ruling out anomalous pulmonary venous drainage
4) ruling out significant mitral regurgitation (MR).
Intraprocedural TEE is not mandatory.

N.B How to distinguish between an ASD device and a patent foramen ovale (PFO) device? Left atrial (LA) disk (green arrow) is larger than Right atrial (RA) disk (yellow arrow), thus it is an ASD device.For a PFO device, RA disk will be larger than LA disk.

Further readings:

A case of Mycobacterium marinum infection in a fisherman

2015-01-23T23:00:00.000+02:00

Historically recognized as “swimming pool” or “fish tank” granuloma.

Clinical features:
Most infections occur 2 to 3 weeks after contact with contaminated water from one of these sources. The lesions are most often small violet papules on the hands and arms that may progress to shallow, crusty ulcerations and scar formation. Lesions are usually singular. However, multiple ascending lesions resembling sporotrichosis can occasionally occur.
Most patients are clinically healthy with a previous local hand injury that becomes infected while cleaning a fish tank or patients may sustain scratches or puncture wounds from saltwater fish, shrimp, fins and other marine life contaminated with
M. marinum. Swimming pools seem to be a risk only when non-chlorinated.

Diagnosis:
Diagnosis is made from culture and histologic examination of biopsy material, along with a compatible history of exposure.

Treatment:

No treatment of choice is recognized for M. marinum. However, successful treatments have traditionally been a two-drug combination of Rifampin (600 mg/day) plus Ethambutol (15mg/Kg) or monotherapy with Doxycycline, Minocycline (100 mg BD), Clarithromycin (500mg BD) or Trimethoprim-Sulfamethoxazole given for a minimum of 3 months. Clarithromycin has been used increasingly because of good clinical efficacy and minimal side effects, although published experience is limited.

The following is the case of a fisherman who got injured while handling his fishing cage and presented with extensive papular lesions on his forearm. He was started on two drug-combination therapy for 5 months.

The second image is the same patient after 3 months of treatment.

COPD exacerbation - definition, assessment, management

2015-01-19T22:35:00.000+02:00

COPD exacerbation:

Definition:

Exacerbation of COPD is defined as an acute episode, characterized by the worsening of the patient’s respiratory symptoms that is beyond normal daily variations and that will eventually lead to a change in his medications.
Those having 2 or more exacerbations per year are known as “frequent exacerbators”.

Precipitating factors:

1) Respiratory tract infections – viral or bacterial. Most common cause. There may be an increased bacterial burden in the lower airways or new strains of bacteria are acquired during an exacerbation. Commonly implicated viruses

include rhinovirus, respiratory syncytial virus, coronavirus and influenza virus.

2) Air pollution.

3) Interruption of maintenance therapy.

4) Unknown causes – 30% cases.

Diagnosis:

Diagnosis should be made clinically whereby the patient complains of an acute aggravation of his symptoms out of proportion to his day to day variations.

Assessment:

Medical history:

1) Severity of COPD before this exacerbation

2) Duration of the worsening or any new symptoms

3) Number of previous exacerbations or hospitalizations

4) Associated comorbidities

5) Present medications

6) Previous uses of mechanical ventilation.

Clinical examination:

1) Use of accessory respiratory muscles or paradoxical chest wall movements

2) Development of central cyanosis or exacerbation of pre-existing cyanosis

3) Change in mental status

4) Development of peripheral edema

5) Hemodynamic instability

Tests to assess severity include:

1) Pulse oximetry – good for monitoring.

2) Arterial blood gases and acid base status – shows whether there is an acute or acute on chronic respiratory failure.

3) Chest radiography – excludes alternative diagnoses and can show infections.

4) EKG – may help to assess any pre-existing cardiac problems.

5) Complete blood count – white cells may be elevated, hematocrit may be elevated

6) Blood biochemistry.

Spirometry is difficult to perform during an exacerbation and it may not be of enough accuracy. Therefore it is not recommended.

Treatment:

More than 80% of cases can be managed as outpatients but if the following conditions are seen, it is better to admit and if necessary give intensive care:

1) Dyspnea occurring at rest

2) Old age

3) Frequent exacerbator

4) Failure of response to change in/addition of medication to control the exacerbation

5) New onset of arrhythmias or peripheral edema.

Medical therapy consists of:

1) Short acting inhaled bronchodilators – beta-2 agonists with or without anti-cholinergics are preferred. It is better to use a nebulizer as the patient usually is dyspneic and lacks coordination to inhale from a metered-dose inhaler. IV methylxanthines are considered as second line of therapy for bronchodilation and are to be used only in selected cases, especially if there is poor response to short acting inhaled bronchodilators.

2) Corticosteroids – oral prednisone 40 mg/day for 5 days has been shown to shorten recovery time and improve lung function as well as arterial hypoxemia.

3) Antibiotics – these are indicated if the patient has clinical signs of bacterial infections e.g. increased in sputum purulence. Procalcitonin III may help to indicate antibiotic therapy as it is increased in cases of bacterial infections. Usually in the following conditions antibiotics should be considered:

- 3 cardinal symptoms present: increase in dyspnea, sputum volume and sputum purulence,

- 2 cardinal symptoms, with purulence being one of the symptoms,

Antibiotics are recommended for 5-10 days.

4) Adjunct therapies – proper control of comorbidities is advised. Thromboprophylactic measures should be enhanced.

Respiratory support:

1) Oxygen therapy: Oxygen is titrated to correct the hypoxemia of the patient aiming to achieve a saturation of 88-92%. Usually Venturi masks are preferred to nasal prongs. After 30-60 minutes of oxygen therapy, arterial blood gases should be checked.

2) Non-invasive mechanical support

3) Invasive mechanical support.

Hyperemesis gravidarum - definition, epidemiology, pathophysiology, complications, management

2015-01-09T16:18:00.000+02:00

Definition:

Mild to moderate nausea and vomiting are seen commonly until approximately 16 weeks in most pregnant ladies. Although nausea and vomiting tend to be worse in the morning, thus erroneously termed morning sickness, they frequently continue throughout the day. In some cases, however, it is severe and unresponsive to simple dietary modification and antiemetics.

Hyperemesis gravidarum is defined as vomiting sufficiently severe to produce weight loss, dehydration, alkalosis from loss of hydrochloric acid and hypokalemia. Rarely, acidosis from partial starvation and transient hepatic dysfunction develop.

Modified PUQE scoring index (Pregnancy-Unique Quantification of Emesis and Nausea) can be used to quantify the severity of nausea and vomiting.

Epidemiology:

There appears to be an ethnic or familial predilection. The hospitalization rate for hyperemesis is around 0.5 to 0.8%. Hospitalization is less common in obese women. In women hospitalized in a previous pregnancy for hyperemesis, up to 20 percent require hospitalization in a subsequent pregnancy.

Pathophysiology:

Hyperemesis appears to be related to high or rapidly rising serum levels of pregnancy-related hormones. The presumed culprits include human chorionic gonadotropin (hCG), estrogens, progesterone, leptin, placental growth hormone, prolactin, thyroxine and adreno-cortical hormones. Some studies have implicated the vestibular system while others have showed some involvement of psychological components.

Other factors that increase the risk for admission include

1) hyperthyroidism,

2) previous molar pregnancy,

3) diabetes,

4) gastrointestinal illnesses and

5) asthma.

For unknown reasons, a female fetus increases the risk by 1.5-fold.

Complications:

Vomiting may be prolonged, frequent and severe.

1) Various degrees of acute renal failure from dehydration are encountered.

2) Life-threatening complications of continuous retching include Mallory-Weiss tears shown in the figure below. Others are esophageal rupture, pneumothorax and pneumomediastinum.

3) At least two serious vitamin deficiencies have been reported with hyperemesis in pregnancy. Wernicke encephalopathy from thiamine (vitamin B1) deficiency is not uncommon. Vitamin K deficiency has been reported causing maternal coagulopathy and fetal intracranial hemorrhage.

The photo shows a Mallory Weiss tear with the endoscope in retroflexion.

Management:

1) Eating small meals at more frequent intervals but stopping short of satiation is valuable. The herbal remedy, ginger, was effective as showed by this meta-analysis published in 2014. Ginger capsules 250 mg 4 times daily.

2) A number of antiemetics given orally or by rectal suppository as first-line agents. When simple measures fail, intravenous crystalloid solutions are given to correct dehydration, ketonemia, electrolyte deficits, and acid-base imbalances. Thiamine, 100 mg, is given to prevent Wernicke encephalopathy. Diclegis (Doxylamine and Pyridoxine (Vitamin B6) ) is the only FDA approved medication for nausea and vomiting in pregnancy.

3) If vomiting persists after rehydration and failed outpatient management, hospitalization is recommended. Antiemetics such as

- Promethazine 12.5-25 mg 4 hourly,

- Prochlorperazine 5-10 mg 6 hourly,

- Metoclopramide 5-10 mg 8 hourly are given parenterally.

With persistent vomiting after hospitalization, appropriate steps should be taken to exclude possible underlying diseases as a cause of hyperemesis (gastroenteritis, cholecystitis, pancreatitis, hepatitis, peptic ulcer and pyelonephritis).

Calcinosis cutis

2014-11-17T19:56:00.001+02:00

Competitive, uncompetitive and non competitive enzyme inhibitors

2014-06-03T21:21:00.000+03:00

(A) Enzyme–substrate complex;

(B) a competitive inhibitor binds at the active site and thus prevents the substrate from binding;

(D) a noncompetitive inhibitor does not prevent the substrate from binding.

Visceral and parietal layer of serous pericardium

2014-06-03T21:03:00.002+03:00

Pericardium

The pericardium is a fibroserous sac surrounding the heart and the roots of the great vessels. It consists of two components,

1) the fibrous pericardium and

2) the serous pericardium.

The fibrous pericardium is a tough connective tissue outer layer that defines the boundaries of the middle mediastinum.

The serous pericardium is thin and consists of two parts:

1) The parietal layer lines the inner surface of the fibrous.

2) The visceral layer adheres to the heart and forms its outer covering.

The parietal and visceral layers of serous pericardium are continuous at the roots of the great vessels. The narrow space created between the two layers of serous pericardium, containing a small amount of fluid, is the pericardial cavity. This is pictured in the diagram above as a fist in a filled balloon. This potential space allows for the relatively uninhibited movement of the heart.

Fibrous pericardium

The fibrous pericardium is a cone-shaped bag with its base attached to the central tendon of the diaphragm

and a small muscular area on the left side of the diaphragm and its apex continuous with the adventitia of the great vessels. Anteriorly, it is attached to the posterior surface of the sternum by sternopericardial ligaments.

These attachments help to retain the heart in its position in the thoracic cavity. The sac also limits cardiac

distention.

Serous pericardium

The parietal layer of serous pericardium is continuous with the visceral layers of serous pericardium around the roots of the great vessels. These reflections of serous pericardium occur in two locations:

1) one superiorly, surrounding the arteries, the aorta and pulmonary trunk;

2) the second more posteriorly, surrounding the veins, the superior and inferior vena cava and the pulmonary veins.

Diaxozide - mechanism of action

2014-04-26T15:44:00.001+03:00

The diagram shows a beta cell of the islet of pancreas and will explain how local factors regulate secretion of insulin from it.
Glucose enters the cell via the GLUT-2 transporter. Inside the cell there is metabolism with the generation of ATP. This causes the ATP-sensitive K+ channel to close, as shown in A.
Closure of this channel leads to cell membrane depolarization. This in turn allows calcium ions to enter the cell via another calcium channel, shown in B. Increased intracellular calcium activates calcium dependent phospholipid protein kinase. This leads to exocytosis of insulin granules.

Diaxozide acts by opening the K+ channel. This leads to loss of K+ and causing membrane hyperpolarization. This prevents Ca2+ from entering, protein kinases are not activated and thus there is no exocytosis of insulin granules...

Prognostic scores in alcoholic hepatitis

2013-12-15T20:20:00.000+02:00

1. Maddrey (modified) Discriminant Function score of greater or equal to 32 indicates a high risk (30-50%) risk of mortality at 30 days. The risk is even higher is there are signs of hepatic encephalopathy. Scores should be repeated at day 7.

2. MELD stands for Model for End stage Liver Disease. It is used to estimate 90 days mortality. Poor prognosis if score is greater than 18. Score should be repeated at day 7.

Effect of weather on COPD

2013-10-06T14:47:00.000+03:00

Exacerbations of COPD are more commonly seen during the winter season (nearly 1.6 times more frequently). The main cause of these exacerbations is infection with the respiratory virus, rhinovirus.
Frequent exacerbations have been shown to lead to a faster decline in the lung function, poorer quality of life and increased mortality.
A recent study showed that COPD exacerbations in colder periods of the year take longer to recover from and are more likely to involve cough or coryzal symptoms. The exacerbations in the cold seasons also have a greater impact on daily activity, with patients spending more time indoors and being more likely to be hospitalized with respiratory viral infection.