Читать книгу Laboratory Assessment of Nutritional Status: Bridging Theory & Practice - MARY LITCHFORD - Страница 17

There are 4 categories of anemias and 4 types of nutritional anemias. Early onset of all of the nutritional anemias are associated with lack of energy, malaise and decreased interest in activities of daily living and lifelong interests. However, each presents a different pattern of laboratory results from a variety of blood tests. More than one type of nutritional anemia can occur at the same time. No one test alone is used to diagnose the nutritional anemias. Because the nutritional anemias can initially appear to be the same, it is important to look at more than one lab test result before recommending a plan for medical nutrition therapy.

Nutritional anemias are categorized using red blood cell indices quantifying the size, weight and hemoglobin concentration of red blood cells. These tests are used to categorize anemias. Table 6 categorizes nutritional anemias by red blood cell indices.

The four types of nutritional anemias are:

•Iron Deficiency Anemia

•Megaloblastic Anemia

•Pernicious Anemia

•Anemia of Chronic and Inflammatory Diseases

Iron Deficiency Anemia

Iron deficiency anemia is most commonly seen in children with low iron intakes. However, approximately 20 percent of women, 50 percent of pregnant women, and 3 percent of men are iron deficient. The DRI for iron for adult males and females 51 years and older is 8 mg/d. For females under the age of 50, the DRI is 18 mg/d. The NHANES data reports that median intakes of iron for adults aged 40 to 59 and 60 years and older are 15.5 mg/day and 14.8 mg/d respectively (Ervin, 2004).

Iron deficiency anemia may be the result of a chronic blood loss, after an acute blood loss, deficient diet, malabsorption of iron or increased need for iron. Decreased stomach acidity, due to overconsumption of antacids, ingestion of alkaline clay, achlorhydria, partial gastrectomy or weight loss surgery may lead to impaired iron absorption and ultimately iron deficiency anemia.

Clinical signs and symptoms include inflammation of the tongue, lips or mucous membranes of the mouth and spooned nails. In its advanced state, it is described as a microcytic hypochromic anemia. Laboratory tests used to diagnose iron deficiency anemia include a low hemoglobin, low hematocrit, low MCV, low serum iron, elevated total iron binding capacity (TIBC), low reticulocyte count, low ferritin, elevated RDW and elevated erythrocyte sedimentation rate. Not all of these tests may be available due to cost restraint. The MCV is the key test to examine once a low hemoglobin and low hematocrit are identified.

Once underlying causes of iron deficiency anemia are identified and addressed, oral iron therapy is preferred, however a multivitamin may be better tolerated. Absorption is best on an empty stomach, but may cause gastric upset (Blackwell, 2001). Remember that the goal of pharmacological intervention is to increase the deficient body components while avoiding a negative impact on the total dietary intake of the patient.

Anemia of chronic and inflammatory diseases

Anemia of chronic and inflammatory diseases develops as a result of an extended infection or inflammation. The anemia usually manifests itself in a similar manner to iron deficiency anemia. While the physical signs and symptoms are the same as iron deficiency, anemia of chronic and inflammatory diseases is a normochromic-normocytic anemia. In anemia of chronic and inflammatory diseases, the lab results are below normal ranges for hemoglobin, hematocrit, serum iron and TIBC. However, the MCV and ferritin are usually normal. The changes in lab test

Table 6. Anemias According to RBC Indices

	Normocytic1, Normochromic2, Anemia •Iron Deficiency (early stages) •Anemia of Chronic and Inflammatory Diseases •Acute Blood Loss •Pernicious Anemia ( about 40% of cases)
	Microcytic3, Hypochromic4 Anemia •Iron Deficiency (advanced)
	Microcytic3 Normochromic1 Anemia • Renal Disease due to loss of erythropoietin
	Macrocytic5, Normochromic1 Anemia •Vitamin B12 / Pernicious Anemia •Folic Acid Deficiency/Megaloblastic Anemia

Key:

¹ Normocytic - normal RBC size

² Normochromic - normal color (normal hemoglobin content)

³ Microcytic - smaller than normal RBC size

⁴ Hypochromic - less than normal color (hemoglobin content)

⁵ Macrocytic - larger than normal RBC size

results are either related to redistribution of iron stores or impaired utilization. A multivitamin supplement with iron or oral iron therapy may be ordered, however, should be carefully monitored for expected outcomes. In cases of true anemia of chronic and inflammatory diseases, the lab values will not improve until the underlying condition resolves.

Other characteristics of anemia of chronic and inflammatory diseases may include slow involuntary weight loss and hypoalbuminemia. Weight loss occurs despite efforts to increase caloric intake. Certain chronic infections and inflammatory diseases cause several changes in the blood cell production system. These include a slightly shortened red blood cell life span and an isolation of iron in inflammatory cells (macrophages) that result in a decrease in the amount of iron available to make RBC. In the presence of these effects, a low-to-moderate grade anemia develops.

Conditions associated with the anemia of chronic and inflammatory diseases include the following:

•Advanced age

•AIDS

•Chronic Bacterial Endocarditis

•Chronic Renal Failure

•Congestive Heart Failure

•Crohn's Disease

•Juvenile Rheumatoid Arthritis

•Osteomyelitis

•Rheumatic fever

•Ulcerative Colitis

Macrocytic anemias

Macrocytic anemias include megaloblastic anemia or folate deficiency and pernicious anemia or vitamin B12 deficiency. The presence of macrocytic RBC requires evaluation of both folate and vitamin B12 status.

The metabolic interrelationship between folate and vitamin B12 may explain why a single deficiency of either leads to the same hematological changes. The most common cause of macrocytic anemia is megaloblastic anemia due to impaired DNA synthesis. Vitamin B12 and folate coenzymes are required for thymidylate and purine synthesis. A deficiency of either or both nutrients retards DNA synthesis that triggers dyspoiesis (abnormal rate of RBC maturation in bone marrow) and pancytopenia (decrease in the production of RBC). While the macrocytic RBC is the hallmark of macrocytic anemia, other rapidly dividing cells are affected. Other physiological changes may include, sore tongue due to glossitis or atrophy of tongue, skin changes, and flattening of intestinal villi (Guyton, 2006).

RNA synthesis is unaffected by a deficiency of folate or vitamin B12 but, there is a build up of cytoplasmic components in a slowly dividing cell making the RBC larger than normal. The primary defect in DNA synthesis caused by folate or vitamin B12 deficiency is a depletion of thymidine triphosphate (dTTP). This leads to retarded mitosis and nuclear maturation. The RBC have shortened life spans and reduced capacity to carry hemoglobin. Iron is stored as serum iron or ferritin rather than in hemoglobin (Guyton, 2006).

The first sign of inadequate folic acid intake is a decrease in serum folate concentration followed by a decrease in erythrocyte folate concentration and a rise in homocysteine levels. When folate supply to the bone marrow becomes rate limiting for erythropoiesis, macrocytic cells are produced. Macrocytic anemia is not evident in the early stages of folate deficiency because of the 120-day lifespan of normal erythrocytes.

When dietary vitamin B12 is deficient, the body cannot convert N⁵methyl THF to the active form of folate, tetrahydrofolate (THF). Without adequate vitamin B12, folate is trapped in an unusable form (Guyton, 2006). When dietary folate is deficient, the same problems occur because there are inadequate amounts of THF needed for the cascade of reactions required for DNA synthesis (Guyton, 2006). A B12 deficiency will eventually cause a folate deficiency because folate cannot be converted into an active form without vitamin B12 (Bostom, 1996).

One of the earliest clinical signs of both folate and vitamin B₁₂ deficiency is hyper-segmentation of > 5 percent of neutrophils. Hyper-segmentation may also occur in uremia, myeloproliferative disorders, myelofibrosis and as a congenital lesion in 1% of the population. More testing is required to differentiate between megaloblastic and pernicious anemia.

The abnormal RBC cannot conform to the size of small capillaries. Instead, they fracture and hemolyze, thus shortening their lifespan. The macrocytic RBC has a reduced capacity to carry hemoglobin. Dietary iron is absorbed by the body and stored as serum iron or ferritin rather than in hemoglobin. Once the folate and/or vitamin B12 deficiency is treated through dietary supplements, the iron stores from the serum iron and ferritin will shift back to the RBC and the hemoglobin and hematocrit will return to normal levels. Homocysteine levels may or may not return to normal levels with folate supplementation.

Megaloblastic Anemia

Megaloblastic anemia is a folate deficiency commonly seen in middle-aged and older adults. It has been associated with an increased risk for heart disease and end stage renal disease because of the association with elevated homocysteine levels (Morrison, 1996; Pancharuniti, 1994; Robinson, 1996). It may be due to increased needs, a deficient diet, malabsorption of folate and/or a vitamin B12 deficiency. Malabsorption of folic acid may occur in individuals with diseases of the small intestine including ileitis, tropical and nontropical sprue, overgrowth of bacteria, hemolytic anemia, liver disease, malnutrition and following biliopancreatic diversion with and without duodenal switch (BPD/DS) weight loss surgery (Aills, 2008).

Some medications are folate antagonists and interfere with nucleic acid synthesis. The most common folate antagonists are anticonvulsants, antimalarials, alcohol, aminopterin and methotrexate. Megaloblastic anemia occurs after approximately 5 months of folate depletion.

The initial clinical signs and symptoms of megaloblastic anemia are low levels of hemoglobin, hematocrit and red cell folate. However, elevated levels of serum iron, MCV, ferritin and homocysteine are common. Falsely elevated concentrations of red cell folate are seen in patients with raised reticulocyte counts and low levels occur in vitamin B12 deficiency. Plasma folate can be used to assess status however; it is affected by recent folate intake.

Treatment for megaloblastic anemia is based on its etiology. Folate supplementation of 1 mg or more daily can compensate for vitamin B12 deficiency in DNA synthesis reversing macrocytic anemia and thereby masking vitamin B12 deficiency. Undiagnosed vitamin B12 deficiency will result in progressive permanent neurological damage including permanent changes in cognitive abilities. Individuals taking known folic acid antagonists will require prescription strength supplemental folate for as long as these medications are taken. Individuals with malabsorption disorders due to disease or weight loss surgery will require supplemental folic acid for a lifetime.

Pernicious Anemia

Pernicious anemia is due to a vitamin B12 deficiency commonly seen in older adults, vegetarians and individuals who have had malabsorptive weight loss surgery. Early signs and symptoms include pallor, weakness, lightheadedness, smooth, sore tongue, diarrhea alternating with constipation, numbness and tingling of extremities, gait abnormalities, personality changes, irritability, confusion, cognitive changes, depression and numbness of the hands and feet. Permanent nerve lining damage and significant cognitive decline will result from an untreated vitamin B12 deficiency.

Absorption and utilization of vitamin B12 is a multi step process. Dietary vitamin B12 is bound to a protein carrier. An acidic environment is required for the body to cleave the protein carrier from vitamin B12. Once vitamin B12 is released from its protein carrier in the stomach, it must form a complex with intrinsic factor (IF) for absorption in the terminal ileum. IF is synthesized in the stomach in the presence of an acidic environment. Without IF, B12 cannot be absorbed, body stores are depleted and the body produces enlarged immature RBC. It is categorized as a macrocytic normochromic anemia, however about 40 percent of the cases are normocytic (Allen, 1990; Carmel, 1996; Koepke, 1997; Pennypacker, 1992).

The ability to absorb and utilize vitamin B12 decreases with age affecting about 20-50 percent of the elderly. The decline in absorption and utilization of vitamin B12 is primarily due to atrophic gastritis and/or gastric mucosa defect resulting in inadequate secretion of IF. Atrophic gastritis results in declining gastric acid and pepsinogen secretions. The increased pH in the gastrointestinal tract decreases intestinal absorption of the cobalamin protein complexes from food. In addition, the reduced acid secretion leads to an alkalinization of the small intestine, which may result in bacterial overgrowth and further decrease the bioavailability of the vitamin.

Other causes of pernicious anemia include history of gastric or ileal resections, weight loss surgery, diseases associated with malabsorption (e.g. Crohn's disease) may cause impaired vitamin B12 absorption. Medications such as proton pump inhibitors or H2 receptor antagonists inhibit the intestinal absorption of vitamin B12.

Plasma vitamin B12 test is a reflection of recent intake rather than vitamin stores. More prolonged vitamin B12 deficiency is measured by either blood or urinary methylmalonic acid (MMA). Elevated serum and urinary MMA levels are direct measure of tissue vitamin B12 activity. Urinary MMA/creatinine ratio is more accurate than the serum MMA as it indicates tissue/cellular vitamin B12 deficiency.

The etiology of vitamin B12 deficiency should be determined for appropriate treatment. Vitamin B12 deficiency can result from either inadequate diet or impaired absorption.

The Schilling test can be used to distinguish insufficient secretion of intrinsic factor from malabsorption syndromes. In this test, radioactive B12 is taken orally and urinary excretion is measured over 24 hours. A flushing dose of unlabeled B12 is given with the labeled B12 to saturate liver storage and enhance labeled B12 excretion.

Normally, >7 percent of the labeled B12 is recovered in the urine. If absorption is low, it is necessary to repeat the test with administration of intrinsic factor. The lab results for pernicious anemia are very similar to megaloblastic anemia. Lower than normal values are seen for hemoglobin, hematocrit and serum B12. However, elevated levels are seen in serum iron, serum folate, ferritin and homocysteine. MCV may be elevated or normal. The only definitive lab test appears to be MMA. This test is elevated in vitamin B12 deficiency and normal in megaloblastic anemia (Van Asselt, 1996; Savage, 1994).

Treatment for pernicious anemia is based on the etiology of the anemia. Oral B12 supplements are effective if the body can produce adequate levels of IF and the pH of the stomach is sufficient to cleave vitamin B12 from its protein carrier. However, if the body is unable to produce IF then daily B12 nasal spray, B12 patch or monthly injections of B12 are recommended. Table 7 summarizes the most commonly used tests to evaluate for different types of anemia. Not all patients’ lab results will follow the pattern provided in Table 7 due to the effects of other diseases or the use of medications. Additional information about each laboratory test is included in the next section of this text.

Table 7. Guide to Anemias

Lab Test	Fe Deficiency	Megaloblastic Anemia (Folate)	Pernicious Anemia (B12)	Anemia of Chronic & Inflammatory Disease
HGB Females Males	<12 gm <14 gm	<12 gm <14 gm	<12 gm <14 gm	<12 gm <14 gm
HCT Females Males	<37% <42%	<37% <42%	<37% <42%	<37% <42%
MCV	<80 μm3	>95 μm3	>95 μm3 or WNL	WNL
MCH	<27 pg	>31 pg	>31 pg	WNL
Serum Fe Females Males	<60 μg/dL <80 μg/dL	>190 μg/dL >180 μg/dL	>190 μg/dL >180 μg/dL	<60 μg/dL <80 μg/dL
TIBC	>460 μg/dL	-	-	<250 μg/dL
Retic Count	> 2%	< 0.5%	< 0.5%	< 0.5%
ESR	elevated	elevated	elevated	elevated
Ferritin Females	<10 ng/mL	>150 ng/mL	>150 ng/mL	WNL or elevated
Ferritin Males	<12 ng/mL	>300 ng/mL	>300 ng/mL	WNL or elevated
Serum B12	normal	decreased	decreased	WNL
Folate	-	<5 ng/mL	>25 ng/mL	WNL or decreased
Hcy	-	increased	increased	WNL
MMA	-	WNL	increased	-

KEY:

HGB=hemoglobin, HCT=hematocrit, MCV=mean corpuscular volume, MCH= mean corpuscular hemoglobin, TIBC=total iron binding capacity, Retic count= reticulocyte count, ESR= erythrocyte sedimentation rate, Hcy=homocysteine, MMA= methylmalonic acid