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Protein S deficiency

Protein S deficiency is a disorder associated with increased risk of thrombosis. more...

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Decreased levels or impaired function of protein S, a vitamin K-dependant physiological anticoagulant, leads to decreased degradation of factor Va and factor VIIIa and an increased propensity to venous thrombosis.

Types

There are three types of hereditary protein S deficiency:

  • Type I - decreased protein S activity: low levels of free protein S, normal levels of bound protein S
  • Type IIa - decreased protein S activity: low levels of free protein S, low levels of bound protein S
  • Type IIb - decreased protein S activity: normal levels of free protein S, normal levels of bound protein S

Decreased activity is present in an acquired form in vitamin K deficiency or treatment with warfarin. This generally also impairs the coagulation system itself (factors II, VII, IX and X), and therefore predisposes to bleeding rather than thrombosis. Protein S levels are also lower in pregnancy and liver disease.

Protein S deficiency is the underlying cause of a small proportion of cases of disseminated intravascular coagulation (DIC), deep venous thrombosis (DVT) and pulmonary embolism (PE).

Hereditary PSD is an autosomal dominant condition, resulting in a 50 precent chance of passing the disease to offspring. Less than half of those diagnosed with PSD will experience thrombosis, and those who do usually are affected only from the age of the late teens onwards. A positive blood test can lead to the loss of health insurance benefits and/or employment, and the social downsides need to be balanced against the actual medical benefit of accurate diagnosis. Screening of young children is usually deferred because early testing is often inaccurate, and it is better to wait until they are old enough to decide for themselves whether they want to be tested.

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Protein-energy malnutrition
From Gale Encyclopedia of Medicine, 4/6/01 by Maureen Haggerty

Definition

Protein-energy malnutrition (PEM) is a potentially fatal body-depletion disorder. It is the leading cause of death in children in developing countries.

Description

PEM is also referred to as protein-calorie malnutrition. It develops in children and adults whose consumption of protein and energy (measured by calories) is insufficient to satisfy the body's nutritional needs. While pure protein deficiency can occur when a person's diet provides enough energy but lacks the protein minimum, in most cases the deficiency will be dual. PEM may also occur in persons who are unable to absorb vital nutrients or convert them to energy essential for healthy tissue formation and organ function.

Although PEM is not prevalent among the general population of the United States, it is often seen in elderly people who live in nursing homes and in children whose parents are poor. PEM occurs in one of every two surgical patients and in 48% of all other hospital patients.

Types of PEM

Primary PEM results from a diet that lacks sufficient sources of protein and/or energy. Secondary PEM is more common in the United States, where it usually occurs as a complication of AIDS, cancer, chronic kidney failure, inflammatory bowel disease, and other illnesses that impair the body's ability to absorb or use nutrients or to compensate for nutrient losses. PEM can develop gradually in a patient who has a chronic illness or experiences chronic semi-starvation. It may appear suddenly in a patient who has an acute illness.

Kwashiorkor

Kwashiorkor, also called wet protein-energy malnutrition, is a form of PEM characterized primarily by protein deficiency. This condition usually appears at the age of about 12 months when breastfeeding is discontinued, but it can develop at any time during a child's formative years. It causes fluid retention (edema); dry, peeling skin; and hair discoloration.

Marasmus

Primarily caused by energy deficiency, marasmus is characterized by stunted growth and wasting of muscle and tissue. Marasmus usually develops between the ages of six months and one year in children who have been weaned from breast milk or who suffer from weakening conditions like chronic diarrhea.

Causes & symptoms

Secondary PEM symptoms range from mild to severe, and can alter the form or function of almost every organ in the body. The type and intensity of symptoms depends on the patient's prior nutritional status and on the nature of the underlying disease and the speed at which it is progressing.

Mild, moderate, and severe classifications have not been precisely defined, but patients who lose 10-20% of their body weight without trying are usually said to have moderate PEM. This condition is also characterized by a weakened grip and inability to perform high-energy tasks.

Losing 20% of body weight or more is generally classified as severe PEM. People with this condition can't eat normal-sized meals. They have slow heart rates and low blood pressure and body temperatures. Other symptoms of severe secondary PEM include baggy, wrinkled skin; constipation; dry, thin, brittle hair; lethargy; pressure sores and other skin lesions.

Kwashiorkor

People who have kwashiorkor often have extremely thin arms and legs, but liver enlargement and ascites (abnormal accumulation of fluid) can distend the abdomen and disguise weight loss. Hair may turn red or yellow. Anemia, diarrhea, and fluid and electrolyte disorders are common. The body's immune system is often weakened, behavioral development is slow, and mental retardation may occur. Children may grow to normal height but are abnormally thin.

Kwashiorkor-like secondary PEM usually develops in patients who have been severely burned, suffered trauma, or had sepsis (tissue-destroying infection) or another life-threatening illness. The condition's onset is so sudden that body fat and muscle mass of normal-weight people may not change. Some obese patients even gain weight.

Marasmus

Profound weakness accompanies severe marasmus. Since the body breaks down its own tissue to use as calories, people with this condition lose all their body fat and muscle strength, and acquire a skeletal appearance most noticeable in the hands and in the temporal muscle in front of and above each ear. Children with marasmus are small for their age. Since their immune systems are weakened, they suffer from frequent infections. Other symptoms include loss of appetite, diarrhea, skin that is dry and baggy, sparse hair that is dull brown or reddish yellow, mental retardation, behavioral retardation, low body temperature (hypothermia), and slow pulse and breathing rates.

The absence of edema distinguishes marasmus-like secondary PEM, a gradual wasting process that begins with weight loss and progresses to mild, moderate, or severe malnutrition (cachexia). It is usually associated with cancer, chronic obstructive pulmonary disease (COPD), or another chronic disease that is inactive or progressing very slowly.

Some individuals have both kwashiorkor and marasmus at the same time. This most often occurs when a person who has a chronic, inactive condition develops symptoms of an acute illness.

Hospitalized patients

Difficulty chewing, swallowing, and digesting food, pain, nausea, and lack of appetite are among the most common reasons that many hospital patients don't consume enough nutrients. Nutrient loss can be accelerated by bleeding, diarrhea, abnormally high sugar levels (glycosuria), kidney disease, malabsorption disorders, and other factors. Fever, infection, surgery, and benign or malignant tumors increase the amount of nutrients hospitalized patients need. So do trauma, burns, and some medications.

Diagnosis

A thorough physical examination and a health history that probes eating habits and weight changes, focuses on body-fat composition and muscle strength, and assesses gastrointestinal symptoms, underlying illness, and nutritional status is often as accurate as blood tests and urinalyses used to detect and document abnormalities.

Some doctors further quantify a patient's nutritional status by:

  • comparing height and weight to standardized norms
  • calculating body mass index (BMI)
  • measuring skinfold thickness or the circumference of the upper arm.

Treatment

Treatment is designed to provide adequate nutrition, restore normal body composition, and cure the condition that caused the deficiency. Tube feeding or intravenous feeding is used to supply nutrients to patients who can't or won't eat protein-rich foods.

In patients with severe PEM, the first stage of treatment consists of correcting fluid and electrolyte imbalances, treating infection with antibiotics that don't affect protein synthesis, and addressing related medical problems. The second phase involves replenishing essential nutrients slowly to prevent taxing the patient's weakened system with more food than it can handle. Physical therapy may be beneficial to patients whose muscles have deteriorated significantly.

Prognosis

Most people can lose up to 10% of their body weight without side effects, but losing more than 40% is almost always fatal. Death usually results from heart failure, an electrolyte imbalance, or low body temperature. Patients with certain symptoms, including semiconsciousness, persistent diarrhea, jaundice, and low blood sodium levels, have a poorer prognosis than other patients. Recovery from marasmus usually takes longer than recovery from kwashiorkor. The long-term effects of childhood malnutrition are uncertain. Some children recover completely, while others may have a variety of lifelong impairments, including an inability to properly absorb nutrients in the intestines and mental retardation. The outcome appears to be related to the length and severity of the malnutrition, as well as to the age of the child when the malnutrition occurred.

Prevention

Breastfeeding a baby for at least six months is considered the best way to prevent early-childhood malnutrition. Preventing malnutrition in developing countries is a complicated and challenging problem. Providing food directly during famine can help in the short-term, but more long-term solutions are needed, including agricultural development, public health programs (especially programs that monitor growth and development, as well as programs that provide nutritional information and supplements), and improved food distribution systems. Programs that distribute infant formula and discourage breast feeding should be discontinued, except in areas where many mothers are infected with HIV.

Every patient being admitted to a hospital should be screened for the presence of illnesses and conditions that could lead to PEM. The nutritional status of patients at higher-than-average risk should be more thoroughly assessed and periodically reevaluated during extended hospital stays or nursing home residence.

Further Reading

For Your Information

    Books

  • Bennett, J. Claude, and Fred Plum. Cecil Textbook of Medicine. Philadelphia: W.B. Saunders, 1996.
  • Fauci, Anthony S., et al, eds. Harrison's Principles of Internal Medicine. 14th ed. New York: McGraw Hill, 1998.

    Organizations

  • American College of Nutrition. 722 Robert E. Lee Drive, Wilmington, NC 20412-0927. (919) 152-1222.
  • American Institute of Nutrition. 9650 Rockville Pike, Bethesda, MD 20814-3990. (301) 530-7050.
  • Food and Nutrition Information Center. 10301 Baltimore Boulevard, Room 304, Beltsville, MD 20705-2351. http://www.nalusda.gov/fnic/.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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