A 20-year-old female was brought to the emergency department with respiratory distress. She gave a history of fever from the previous few days. She was a known alcoholic but used to take alcohol only during episodes of depression.
On examination she was pale, malnourished, agitated and acutely ill. She was in acute respiratory distress. Her pulse was 110/ minute, there was marked tachycardia and a systolic murmur was heard along the left sternal edge. Bilateral crepitations were felt in the lungs, Neck veins were engorged and liver was also enlarged, although non tender. Bilateral foot drop was also there.
What is the probable diagnosis?
What kind of investigations should be carried out to confirm the diagnosis ?
The patient is most probably suffering from cardiac beriberi. The criteria for diagnosing cardiac beriberi is-
1) Signs of heart failure
2) signs of neuropathies
3) history of alcoholism or poor nutritional history,
4) exclusion of other signs of heart failure,
5) low red cell transketolase activity
6) Response by thiamine administration.
The above said patient is a known alcoholic, mal nourished, has heart failure and bilateral foot drop. The probable diagnosis is Thiamine deficiency, that can be confirmed by erythrocyte transketolase activity.
Thiamine deficiency (causing beriberi) is most common among people subsisting on white rice or highly refined carbohydrates in developing countries and among alcoholics. Symptoms include diffuse polyneuropathy, high-output heart failure, and Wernicke-Korsakoff syndrome. Thiamine is given to help diagnose and treat the deficiency.
Thiamine (vitamin B1) is widely available in the diet. Thiamine is involved in carbohydrate, fat, amino acid, glucose, and alcohol metabolism. It is essentially nontoxic. The body cannot produce it and can only store up to 30 mg of thiamine in its tissues. Thiamine is mostly concentrated in the skeletal muscles. Other organs where it is found are the brain, heart, liver and kidneys. The half-life of thiamine is 9-18 days. It is excreted by the kidney.
Pathophysiology of Thiamine deficiency (Beri-Beri)
Deficiency causes degeneration of peripheral nerves, thalamus, mammillary bodies, and cerebellum. Cerebral blood flow is markedly reduced, and vascular resistance is increased.
The heart may become dilated; muscle fibers become swollen, fragmented, and vacuolized, with interstitial spaces dilated by fluid. Vasodilation occurs and can result in edema in the feet and legs. Arteriovenous shunting of blood increases. Eventually, high-output heart failure may occur.
Dry beriberi Nervous system involvement is termed dry beriberi.The neurologic findings can be peripheral neuropathy characterized by symmetric impairment of sensory, motor, and reflex functions of the extremities, especially in the distal lower limbs. Another presentation of neurologic involvement is Wernicke’s encephalopathy, in which an orderly sequence of symptoms occurs, including vomiting, horizontal nystagmus, palsies of the eye movements, fever, ataxia, and progressive mental impairment leading to Korsakoff syndrome.
Wet beriberi is the term used for the cardiovascular involvement of thiamine deficiency. The chronic form of wet beriberi consists of 3 stages. In the first stage, peripheral vasodilation occurs, leading to a high cardiac output state. This leads to salt and water retention mediated through the renin-angiotensin-aldosterone system in the kidneys. As the vasodilation progresses, the kidneys detect a relative loss of volume and respond by conserving salt. With the salt retention, fluid is also absorbed into the circulatory system. The resulting fluid overload leads to edema of the dependent extremities.
Figure- showing edema of the lower extremity.
By the time significant edema occurs, the heart has been exposed to a severely high workload in order to pump the required cardiac output needed to satisfy end organ requirements. Parts of the heart muscle undergo overuse injury, which results in the physical symptoms of tachycardia, edema, and high arterial and venous pressures. These changes can lead to myocardial injury, expressed as chest pain.
Shoshin beriberi A more rapid form of wet beriberi is termed acute fulminant cardiovascular beriberi, or Shoshin beriberi. The predominant injury is to the heart, and rapid deterioration follows the inability of the heart muscle to satisfy the body’s demands because of its own injury. In this case, edema may not be present. Instead, cyanosis of the hands and feet, tachycardia, distended neck veins, restlessness, and anxiety occur.
Infantile beriberi occurs in infants (usually by age 3 to 4 wk) who are breastfed by thiamine-deficient mothers.
Beriberi is observed in developed nations in persons with alcoholism, people on fad diets, persons on long-term peritoneal dialysis without thiamine replacement, persons undergoing long-term starvation, or persons receiving intravenous fluids with high glucose concentration. No accurate statistics are available on the incidence of this condition.
Early symptoms are nonspecific: fatigue, irritability, poor memory, sleep disturbances, precordial pain, anorexia, and abdominal discomfort.
Dry beriberi refers to peripheral neurologic deficits due to thiamine deficiency. These deficits are bilateral and roughly symmetric, occurring in a stocking-glove distribution. They affect predominantly the lower extremities, beginning with paresthesias in the toes, burning in the feet (particularly severe at night), muscle cramps in the calves, pains in the legs, and plantar dysesthesias. Calf muscle tenderness, difficulty rising from a squatting position, and decreased vibratory sensation in the toes are early signs. Muscle wasting occurs. Continued deficiency worsens polyneuropathy, which can eventually affect the arms.
Wernicke-Korsakoff syndrome, which combines Wernicke’s encephalopathy and Korsakoff’s psychosis occurs in some alcoholics who do not consume foods fortified with thiamine. Wernicke’s encephalopathy consists of psychomotor slowing or apathy, nystagmus, ataxia, ophthalmoplegia, impaired consciousness, and, if untreated, coma and death. It probably results from severe acute deficiency superimposed on chronic deficiency. Korsakoff psychosis consists of mental confusion, dysphonia, and confabulation with impaired memory of recent events. It probably results from chronic deficiency and may develop after repeated episodes of Wernicke’s encephalopathy.
Cardiovascular (wet) beriberi is myocardial disease due to thiamine deficiency. The first effects are vasodilation, tachycardia, a wide pulse pressure, sweating, warm skin, and lactic acidosis. Later, heart failure develops, causing orthopnea and pulmonary and peripheral edema. Vasodilation can continue, sometimes resulting in shock.
Infantile beriberi– Heart failure (which may occur suddenly), aphonia, and absent deep tendon reflexes are characteristic.
Because thiamine is necessary for glucose metabolism, glucose infusions may precipitate or worsen symptoms of deficiency in thiamine-deficient people.
- Lack of thiamine intake
- Diets consisting mainly of the following:
- Food containing a high level of thiaminase, including milled rice, raw freshwater fish, raw shellfish, and ferns
- Food high in anti-thiamine factor, such as tea, coffee, and betel nuts
- Processed food with a content high in sulfite, which destroys thiamine
- Alcoholic state
- Starvation state
- Diets consisting mainly of the following:
- Increased consumption states
- Diets high in carbohydrate or saturated fat intake
- Fever – severe infection
- Increased physical exercise
- Increased depletion
- Diuretic therapies
- Peritoneal dialysis
- Hyperemesis gravidarum
- Decreased absorption
- Chronic intestinal disease
- Gastric bypass surgery
- Malabsorption syndrome – Celiac and tropical sprue
- Folate deficiency – For example, in patients undergoing chemotherapy with high-dose methotrexate
- Thiamine serves as a coenzyme (in the form of thiamine pyrophosphate) in a variety of metabolic processes. In these processes, thiamine pyrophosphate is regenerated via the donation of a proton from the reduced form of nicotinamide adenine dinucleotide (NADH).
- Folic acid is essential to having enough dihydrofolate reductase to regenerate NADH from its oxidative form. This regeneration allows NADH to continue to be present to regenerate thiamine pyrophosphate without being consumed in the process.
- If folic acid is deficient in cells, it causes an indirect thiamine deficiency, because thiamine is present but cannot be activated.
Diagnosis is usually based on a favorable response to treatment with thiamin in a patient with symptoms or signs of deficiency. Similar bilateral lower extremity polyneuropathies due to other disorders (eg, diabetes, alcoholism, vitamin B12 deficiency, heavy metal poisoning) do not respond to thiamin. Single-nerve neuritides (mononeuropathy—eg, sciatica) and multiple mononeuropathy (mononeuritis multiplex) are unlikely to result from thiamin deficiency.
Electrolytes, including Mg, should be measured to exclude other causes. For confirmation in equivocal cases, erythrocyte transketolase activity and 24-h urinary thiamine excretion may be measured.
Diagnosis of cardiovascular beriberi can be difficult if other disorders that cause heart failure are present. A therapeutic trial of thiamin can help.
- Supplemental thiamine, with dose based on clinical manifestations
For mild polyneuropathy, thiamine 10 to 20 mg once/day is given for 2 wk. For moderate or advanced neuropathy, the dose is 20 to 30 mg/day; it should be continued for several weeks after symptoms disappear. For edema and congestion due to cardiovascular beriberi, thiamine 100 mg IV once/day is given for several days. Heart failure is also treated.
For Wernicke-Korsakoff syndrome, thiamine 50 to 100 mg IM or IV bid must usually be given for several days, followed by 10 to 20 mg once/day until a therapeutic response is obtained. Anaphylactic reactions to IV thiamine are rare. Symptoms of ophthalmoplegia may resolve in a day; improvement in patients with Korsakoff psychosis may take 1 to 3 mo. Recovery from neurologic deficits is often incomplete in Wernicke-Korsakoff syndrome and in other forms of thiamine deficiency.
Because thiamine deficiency often occurs with other B vitamin deficiencies, multiple water-soluble vitamins are usually given for several weeks. Patients should continue to consume a nutritious diet, supplying 1 to 2 times the daily recommended intake (DRI) of vitamins; all alcohol intake should stop.
The prognosis for beriberi is usually good, unless patients have established Korsakoff syndrome. When patients have progressed to this stage, the degree of damage is only minimally reversible.Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!