Nutritional Disorders and Lab Values

Question 1

Albumin

Answer 1

• most abundant protein found in blood
• synthesized as preproalbumin in the liver
• average serum concentration 4 g/dL

Question 2

Albumin Functions

Answer 2

• maintains oncotic pressure in the vascualr system
• transport
• competitively binds calcium ions

Question 3

Albumin Functions - Oncotic Pressure

Answer 3

• Because of its high concentration, albumin tends to pull water into the circulatory system.
• This role of albumin is about three-fold greater than all other blood proteins combined.
• Consequently, a decrease in serum albumin can lead to edema because water then accumulates in interstitial spaces.

Question 4

Albumin Functions - Transport

Answer 4

•The structure of albumin allows it to nonspecifically bind lipophilic molecules such as free fatty acids, thyroid hormone and steroid hormones.

• As you will learn later, many hormones have their own specific binding proteins. However, the transport of free fatty acids to the liver and muscle depends solely on albumin.
• Fatty acids, in the form of triacylglycerols, are transported in the circulation via chylomicrons (dietary) or very low-density lipoproteins (endogenous system).

•Albumin transports unconjugated bilirubin to the liver following the breakdown of the heme moiety from hemoglobin

-. Severe hypoalbuminemia therefore can lead to jaundice due to accumulation of unconjugated bilirubin in tissues.

• Albumin also transports bound calcium.
• Many medications are transported by albumin.
• Those most tied to albumin transport include NSAIDS (non-steroidal anti-inflammatory drug), warfarin (anticoagulant), digoxin (treatment of congestive heart failure), and midazolam (short-acting benzodiazepine).
• A change in the concentration of serum albumin particularly affects the half-life of these and other medications. Hence under conditions of hypoalbuminemia the concentration of the medication free in solution is increased. While this may produce a more acute effect of the medication, its metabolism will be increased leading to a shorter half-life and hence a shorter duration of its effect.

Question 5

Albumin Functions - Calcium

Answer 5

•Measured total calcium in the blood includes that bound to albumin and the circulating free ionic calcium (Ca2+), the latter being about 50% of the total.

These two forms are NOT in equilibrium. The bound calcium but not Ca2+ depends on the amount of albumin in the blood.

•Because albumin is abundant in the blood, a change in albumin concentration affects the estimation of circulating Ca2+

Question 6

Corrected Calcium

Answer 6

• Normally, a lab value for total calcium can be used to estimate the free Ca2+ concentration assuming that blood albumin is in a normal range. However, when the concentration of albumin is outside the normal range (i.e., either high or low), the reported total calcium value must be corrected.
• For instance, if the albumin concentration is below normal (hypoalbuminemia) then the total calcium value will be decreased below normal. One then would incorrectly assume that the free Ca2+ also is below normal. However, because the ionic Ca2+ concentration does not depend on the bound form, the total value must be corrected for the decreased amount of bound calcium. The equation to correct for calcium is:

Corrected calcium (mg/dL) = total measured (mg/dL) +0.8 * (4 – [serum albumin]g/dL)

Question 7

Hypoalbuminemia is not a useful marker of acute liver disease because…

Answer 7

…it takes several weeks of impaired production to observe a decrease in serum albumin. Even with chronic liver disease more than 50% of liver function needs to be compromised before a decline in serum albumin is detected. Therefore, albumin is not a sensitive marker for liver dysfunction.

Question 8

Is albumin a reasnable marker for nutrition?

Answer 8

It is questionable whether albumin is a reasonable marker for nutrition. Although decreased albumin can be seen with morbidity and mortality associated with malnutrition, the literature shows inconsistent results comparing protein intake and serum albumin in adults.

Question 9

Protein Malnutrition

Answer 9

• In the short term, individuals with inadequate protein intake degrade their muscle protein, in part, to provide the liver with amino acids for albumin synthesis.
• Over time severe protein malnutrition results in decreased production of albumin. The extent of hypoalbuminemia depends on the severity of the protein malnutrition.

Question 10

Hypoalbuminemia

Answer 10

•Serum albumin is decreased by liver disease. Other causes include intravascular volume overload, protein malnutrition, nephrotic syndrome (increased excretion), heart failure and inflammatory responses (most common cause).

Question 11

Hyperalbuminemia

Answer 11

• Severe or chronic dehydration causes hyperalbuminemia because of decreased fluid volume.
• Though severe zinc deficiency is rare, its occurrence can lead to hyperalbuminemia because this condition mimics dehydration as a result of cell swelling due to increased intake of water (hypotonicity).
• Excessive protein intake also can lead to overproduction of albumin.

Question 12

Prealbumin

Answer 12

• transthyretin
• carrier protein for both thyroxine (T₄) and Vitamin A
• Prealbumin carries about 10% of the total thyroxine, albumin carries about 20% and the majority (~70%) is carried by thyroxine binding globulin.
• Similarly, most vitamin A is carried by a specific retinol binding protein (see session: Vitamin A)

Question 13

Prealbumin Values

Answer 13

•the limited role of prealbumin equates to a small pool in the blood

-20-40 mg/dL (about 1% of albumin concentration)

• Because the concentration of prealbumin is so low, serum amounts are sensitive to pathological changes that decrease its production.
• Prealbumin decreases in response to liver disease.
• More importantly, it responds rapidly, unlike albumin, to protein deficiency in individuals with protein-energy malnutrition.
• The short half-life of prealbumin (2 to 4 d vs 20 d for albumin) accounts for its high sensitivity to nutritional status.
• Prealbumin measurements can assess whether hemodialysis patients require nutritional intervention and prealbumin decreases in response to short-term changes due to inflammatory response.
• The extent of decreased prealbumin depends on the severity of the protein malnutrition

Question 14

Kwashikor

Answer 14

• Children with Kwashiorkor suffer from protein malnutrition and may occur when children are weaned and placed solely on solid foods.
• The condition results not from a case of childhood neglect but from finances since foods rich in carbohydrates are generally much cheaper than foods containing quality protein.
• Kwashiorkor is rarely seen in the United States.
• Their condition is characterized by edema, decreased muscle mass, diarrhea, failure to thrive, changes in hair color and/or texture, lethargy, protruding abdomen, and dermatitis often manifesting as a rash.
• The edema is a hallmark of the hypoalbuminemia as discussed above.
• Dietary protein deficiency causes increased muscle protein breakdown and hence muscle loss.
• Low caloric intake contributes to lethargy.
• The protruding abdomen is caused by hepatomegaly.
• Other symptoms likely relate to vitamin and mineral deficiencies.
• Tests for these children may include a variety of measurements besides prealbumin including BUN, CBC, creatinine clearance/serum creatinine (to evaluate kidney damage), total protein concentrations.

Question 15

Management of Kwashiorkor

Answer 15

• Treatment of Kwashiorkor requires increased protein intake and total calories to correct the condition.
• Vitamin and mineral supplementation is essential.
• Depending on how reduced their caloric intake had been, GI function may be less than normal thereby initially making it necessary to gradually to return to what should be a normal intake of food.
• Even with early intervention, the true potential growth and height of the child never will be achieved.
• When treatment is delayed until late stages, the child may be left with permanent mental and physical deficiencies.

Question 16

Marasmus

Answer 16

• Marasmus, in contrast to Kwashiorkor, constitutes a complete energy malnutrition.
• Patients exhibit tissue and muscle wasting and loss of subcutaneous fat.
• While edema may occur, it is not a consistent characteristic as for patients with Kwashiorkor.

Question 17

CRP

Answer 17

• Prealbumin is a sensitive marker for not only malnutrition but also for acute inflammation. Consequently, when measuring prealbumin as a marker of protein malnutrition, an inflammatory-specific marker also must be measured to rule out a potential effect of inflammation causing hypoprealbuminemia.
• CRP is measured for this assessment. CRP binds to phosphocholine on the surface of dead or dying cells allowing for recognition of foreign pathogens because binding facilitates activation of the immune complement system.
• This system helps phagocytic cells and antibodies remove the pathogens, aiding in host defense and clearance of apoptotic and necrotic cells.
• The primary effect seems to be anti-inflammatory.
• Various studies have been conducted in which CRP measurements have been used to evaluate an individual’s ‘inflammatory state’.
• Some foods are considered ‘proinflammatory’ and include refined carbohydrates (e.g., white rice; white bread; sugary soft drinks), common cooking oils (high omega-6 fatty acids but low omega-3), trans-fatty acids (e.g., in deep-fried foods) and processed meats. Individuals who are more physically active, follow a Mediterranean diet plan, maintain lower BMI, BP, blood glucose and triacylglycerols, have a higher HDL, avoid smoking, and/or exhibit less hypertension, have CRP concentrations in a lower range (3.0 mg/L) compared to those who score poorly in these areas.

Question 18

Homocystine

Answer 18

•Some patients with arteriosclerosis have significantly higher plasma homocysteine concentrations (homocystinemia) than do controls.

• This observation suggests a role for homocysteine in the pathogenesis of arteriosclerosis.
• Additional evidence for this association includes B vitamin supplements significantly decrease plasma homocysteine concentrations, persons with low plasma B vitamin concentrations and low dietary intake of B vitamins have an increased risk for heart disease,and folate and vitamin B12 deficiency are common in populations at high risk for heart disease, e.g., the elderly, smokers and alcoholics.
• The biochemical mechanisms by which homocysteine may potentiate cardiovascular disease are not understood, but may involve oxidative damage to lipoproteins and endothelia, as well as impaired platelet function.
• Since the metabolism of homocysteine requires folate, vitamins B12 and B6, deficiencies in any of these will increase plasma homocysteine.
• However, providing these vitamins to lower homocysteine as a means of decreased disease risk remains controversial as is the association between plasma homocysteine and vascular complications.

Question 19

Magnesium

Answer 19

• Magnesium, the fourth most abundant mineral in the body, has multiple functions essential to good health.
• Less than 1% of Mg is in the blood with the remainder in cells of tissues and organs with about 50% found in bone.
• Magnesium is required for more than 300 biochemical reactions in the body, especially those that require ATP.

-ATP must form a complex with Mg2+ to be biologically functional.

• Green vegetables are an excellent source of magnesium because it complexes with chlorophyll.
• Refining white flour causes loss of the magnesium rich portion so that whole grain flour contains more magnesium.
• Halibut, almonds and soybeans are also good sources.

Question 20

Magnesium Functions

Answer 20

• energy metabolism (complex with ATP)
• keeping bones strong
• maintaining normal muscle and nerve function
• protein synthesis
• promoting normal blood pressure
• regulating blood sugar concentration
• supporting a functional immune system
• sustaining a steady heart rhythm

Question 21

Magnesium - Muscle Function

Answer 21

•Mg deficiency as a consequence of alcohol abuse can contribute to severe weakness and ataxia in the limbs

Question 22

Magnesium - Hypertension

Answer 22

• Diets that are good sources of Mg and K have been associated with lower BP. The DASH diet (Dietary Approaches to Stop Hypertension) emphasizes consumption of fruits, vegetables, and low-fat dairy foods; these are high in magnesium, potassium, and calcium, and low in sodium and fat.
• High BP reportedly is significantly lowered in patients who followed the DASH diet.

Question 23

Magnesium - Diabetes

Answer 23

• Mg may affect the release of and response to insulin. Indeed Type 2 DM is often associated with low Mg.
• Hypomagnesemia may worsen or be a consequence of insulin resistance.
• The hyperglycemia associated with diabetes increases urine output and hence may cause increased Mg excretion.
• Monitoring of women for 18 years and men for 12 years showed that the risk for developing Type 2 diabetes was greater in both men and women when Mg intake was low with this significant effect seen in a shorter time period for men than for women.
• However, some studies suggested no benefit from higher Mg intake. Hence further research is needed to examine more closely the association between blood Mg, dietary intake, and Type 2 diabetes.
• Still there seems to be no harm in encouraging patients with a low Mg intake to increase it.

Question 24

Magnesium - Osteoporosis

Answer 24

•Magnesium deficiency may be an additional risk factor for postmenopausal osteoporosis. This effect is likely related to the observation that Mg deficiency can lead to hypocalcemia. “Overall, controlling and maintaining magnesium homeostasis represents a helpful intervention to maintain bone integrity.”

Question 25

Hypomagnesemia

Answer 25

• The health status of the digestive system and the kidneys significantly influences magnesium status.
• GI disorders that impair absorption (e.g., Crohn’s disease; gluten sensitive enteropathy, regional enteritis, and intestinal surgery) can limit the body’s ability to absorb magnesium and can lead to a deficiency in extreme cases.
• Chronic or excessive vomiting and diarrhea can cause a deficiency through less absorption.
• Use of tetracycline antibiotics could cause a deficiency of Mg and decreased effectiveness of the medication because Mg binds tetracycline in the gut thus decreasing the absorption of both.
• Hypomagnesemia also results from excessive excretion.

-Diuretics, certain anti-neoplastic medications and antibiotics such as gentamicin and amphotericin may increase the loss via the urine so that taking these medications over long periods of time may contribute to magnesium depletion.

• Hypomagnesemia can also occur in cases of poorly controlled diabetes and alcohol abuse.
• Early signs of Mg deficiency include loss of appetite, nausea, vomiting, fatigue, and weakness.
• As the condition worsens the patient develops numbness, tingling, muscle contractions and cramps, seizures, personality changes, abnormal heart rhythms, and coronary spasms.
• A severe deficiency can result in hypocalcemia and hypokalemia. Additionally, chronically low Ca and K may be a sign of Mg deficiency.

Question 26

Hypermanesemia

Answer 26

•Magnesium-containing antacids and laxatives, when used frequently in large doses, can lead to excessive consumption of magnesium and hence cause hypermagnesemia. Symptoms include diarrhea and cramping.

Question 27

Zinc

Answer 27

•Zinc is an essential mineral that is naturally present in some foods.

• The best sources of zinc include red meat, poultry and fortified cereals [oysters have by far the highest zinc content; almost 9 times more per serving than beef].
• Most infants (especially those who are formula fed), children, and adults in the US consume recommended amounts of zinc according to national surveys.
• However, zinc intake among older adults might be marginal; 35-45% of adults over age 60 had intakes below estimated average requirement.
• Zinc functions include cell division, cell metabolism, DNA synthesis, immune function, protein synthesis and wound healing.
• With regard to immune function, zinc is necessary for macrophage and, neutrophil function, and natural killer cell activity. Zinc is needed to activate T-lymphocytes so that low Zn leads to reduced lymphocyte proliferation.

Question 28

Zinc Deficiency

Answer 28

• Deficiency of zinc is not common and usually is due to inadequate zinc intake or absorption, increased losses of zinc from the body, or increased requirements for zinc.
• GI and other diseases (e.g., ulcerative colitis, Crohn’s disease, short bowel syndrome) lead to decreased absorption and hence loss from the GI tract.
• Malabsorption syndrome, chronic diarrhea, and chronic liver disease can also contribute to zinc deficiency.
• Vegetarians have a lower bioavailability of zinc in their diets, in part because phytates, which are found in whole-grain breads, cereals, and legumes, bind zinc thereby inhibiting its absorption leading to decreased bioavailability.
• In pregnant women, the risk of Zn deficiency is marginally low at the outset because of the high fetal requirements for Zn (cell division, DNA and protein synthesis).
• Older infants who are exclusively breastfed, Zn intake may be insufficient after 7 months due to increased requirement. Hence the breast milk must be supplemented with formula or foods.
• Zinc deficiency in children is associated with growth retardation. Up to 50% of alcoholics may have some degree of zinc deficiency because alcohol decreases absorption (see also Mg) and increases excretion.
• Generally, zinc deficiency can lead to loss of appetite and of course, loss of its beneficial roles.

-For instance, deficiency is associated with diminished immune function.

• When the deficiency is severe, the patients exhibit hair loss; delayed sexual maturation; impotence, hypogonadism (males), dysgeusia (taste abnormality), anosmia (lack of functioning olfaction) and mental lethargy.
• A deficiency can lead to delayed wound healing.
• Zinc is needed to maintain integrity of the skin.
• Chronic leg ulcers are associated with low Zn and may be treated with Zn supplements.

•Acute diarrhea can be caused by zinc deficiency that can lead to mortality in children.

-The diarrhea is a result of increased susceptibility to infections that cause diarrhea as a secondary consequence of decreased immune function.

Question 29

Zinc Interactions with Medications

Answer 29

• Zinc interferes with absorption of antibiotics either when the antibiotic is taken less than 2h before or less than 6h after zinc ingestion.
• Zinc interacts with penicillamine used in the treatment of rheumatoid arthritis. Diuretics increase Zn excretion leading to possible deficiency.

Question 30

Copper

Answer 30

• Copper, an essential mineral, is naturally present in some foods and is available as a dietary supplement.
• It is a cofactor for several enzymes (known as “cuproenzymes”) involved in energy production, iron metabolism, neuropeptide activation, connective tissue synthesis, and neurotransmitter synthesis.
• One abundant cuproenzyme is ceruloplasmin (CP), which plays a role in iron metabolism and carries more than 95% of the total copper in healthy human plasma.
• Copper is also involved in many physiologic processes, such as angiogenesis, neurohormone homeostasis, and regulation of gene expression, brain development, pigmentation, and immune system functioning.

-In addition, defense against oxidative damage depends mainly on the copper-containing superoxide dismutases.

Question 31

High Levels of Copper

Answer 31

• Chronic exposure to high levels of copper can result in liver damage and gastrointestinal symptoms (e.g., abdominal pain, cramps, nausea, diarrhea, and vomiting).
• Copper toxicity is rare in healthy individuals who do not have a hereditary copper homeostasis defect.
• However, copper toxicity has been reported in people who consume water containing high levels of copper as a result of stagnant water in copper-containing pipes and fixtures as well as copper alloys in water distribution systems and household plumbing that allow copper to leach into water.

Question 32

Wilson’s Disease

Answer 32

• People with Wilson’s disease, a rare, autosomal recessive disease, have a high risk of copper toxicity.
• Wilson’s disease is caused by a mutation in ATP7B, that encodes for a coppertransporting ATPase.
• The copper-transporting ATPase is found primarily in the liver, with smaller amounts in the kidneys and brain. It plays a role in the transport of copper from the liver to other parts of the body.
• A shortage of functional protein, leads to abnormally high tissue levels of copper as a result of defective copper clearance.
• People with this disease can develop neurologic and liver damage that can result in cirrhosis.
• Patients can also develop acute hepatitis, hemolytic crisis, and liver failure.
• Treatment requires lifelong copper chelation therapy or high doses of zinc to prevent permanent organ damage in these patients.