Solving Puzzles of Laboratory Data Interpretation Evaluation of

Solving Puzzles of Laboratory Data Interpretation

Evaluation of Visceral Protein Status • Affected by numerous other factors, including hydration status, chronic illness, acute phase response • May have low sensitivity/specificity • However, low serum albumin and acute phase proteins are associated with increased complications and length of stay in hospitalized patients; probably an index of severity of illness

Preoperative Albumin as a Predictor of Risk in Elective Surgery Patients • Retrospective review of 520 patients with preoperative serum albumin measurements • Preoperative albumin correlated inversely with complications, length of stay, postoperative stay, ICU stay, mortality, and resumption of oral intake • S. albumin levels <3. 2 were predictive of risk – Kudsk et al, JPEN, 2003

Role of Visceral Protein Measurement in Nutrition Screening and Assessment • Low values in critically ill patients a measure of severity of illness • Is a valuable predictor of morbidity/mortality in hospitalized and LTC patients • Can be used to identify elective surgery patients who could benefit from nutrition intervention • Sequential measurements may reflect changes/improvement of nutritional status

Serum Albumin • Normal: 3. 5 -5. 0 g/d. L • Half-life approximately 14 -20 days • Decreased by: APR (in inflammation, infection, injury, surgery, cancer); severe liver failure, redistribution, intravascular volume overload, third spacing, pregnancy; losses in nephrotic syndrome, burns, protein losing enteropathies, exudates • Increased by: intravascular volume depletion, intravenous albumin or plasminate, anabolic steroids

Serum Transferrin • Normal: 200 -400 mg/d. L • Half-life: approximately 8 -10 days • Decreased by: APR, chronic or end-stage liver disease, uremia, protein-losing states, intravascular volume overload, high-dose antibiotic tx, iron overload, severe zinc deficiency, PCM • Increased by: iron deficiency, chronic blood loss, pregnancy, intravasclar volume depletion, acute hepatitis, oral contraceptives, estrogen

Prealbumin (transthyretin, Thyroxin. Binding Prealbumin) • Normal: 16 -40 mg/d. L • Half-life: 2 -3 days • Decreased by: APR, end stage liver disease, untreated hyperthyroidism, nephrotic syndrome, severe zinc deficiency • Increased by: moderate increase in acute or chronic renal failure, anabolic steroids, possibly glucocorticoids

Retinol-Binding Protein • Normal: 2. 7 -7. 6 mg/d. L • Half-life: approximately 12 hours • Decreased by: hyperthyroidism, chronic liver disorders, APR, cystic fibrosis, vitamin A or severe zinc deficiency • Increased by renal failure, glucocorticoids, acute or early liver damage

C-Reactive Protein (CRP) • Monitors the presence, intensity, and recovery from an inflammatory process • Good indicator of the APR and sensitive for diagnosing infection • Not useful as a nutritional marker, however can be used to evaluate effect of APR on nutritional markers such as visceral proteins

CRP • Normal: <0. 8 mg/d. L (<8 mg/L) • Rises within hours of an acute stimulus • Decrease in CRP of >50 mg/L between admission and day 4 is a good predictor of recovery • As the ACP wanes, expect to see CRP decline • As CRP declines, sensitive visceral proteins should increase

Lipoprotein Profile • Measures total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides • 8 -12 hour fast allows chylomicrons to clear • Friedenwald formula for calculating LDL-C = (TC) – (HDL-C) – (TG/5)

Lipoprotein Profile Confounders • Lipids decline significantly 24 hours after an acute MI or other event • Lipid profiles should be done either within 24 hours of an acute myocardial event or several weeks out • Lipids measured after major surgery will be artificially low • Very low total cholesterol may indicate malnutrition • Estrogen decreases serum cholesterol; pregnancy and menopause increase serum cholesterol

ATP III Screening Guidelines New Recommendation for Screening/Detection • Complete lipoprotein profile preferred – Fasting total cholesterol, LDL, HDL, triglycerides • Secondary option – Non-fasting total cholesterol and HDL – Proceed to lipoprotein profile if TC 200 mg/d. L or HDL <40 mg/d. L

Three Categories of Risk that Modify LDL-Cholesterol Goals Risk Category LDL Goal (mg/d. L) CHD and CHD risk equivalents <100 Multiple (2+) risk factors <130 Zero to one risk factor <160

Major Risk Factors for CHD • Cigarette smoking • Hypertension (BP >140/90 mm. Hg or on antihypertensive medication) • Low HDL cholesterol (<40 mg/d. L) • Family history of premature CHD (CHD in male first degree relative <55 years; • CHD in female first degree relative <65 years) • Age (men >45 years; women >55 years)

CHD Risk Equivalents • • • Clinical CHD Symptomatic carotid artery disease Peripheral arterial disease Abdominal aortic aneurysm. Diabetes

ATP III Lipid and Lipoprotein Classification LDL Cholesterol (mg/d. L) <100 Optimal 100– 129 Near optimal/above optimal 130– 159 Borderline high 160– 189 High 190 Very high

ATP III Lipid and Lipoprotein Classification (continued) HDL Cholesterol (mg/d. L) <40 60 Low High

ATP III Lipid and Lipoprotein Classification (continued) Total Cholesterol (mg/d. L) <200 Desirable 200– 239 Borderline high 240 High

Specific Dyslipidemias: Elevated Triglycerides Classification of Serum Triglycerides • • Normal <150 mg/d. L Borderline high 150– 199 mg/d. L High 200– 499 mg/d. L Very high 500 mg/d. L

Causes of High Triglycerides ( 150 mg/d. L) • • Obesity and overweight Physical inactivity Cigarette smoking Excess alcohol intake

Causes of High Triglycerides • High carbohydrate diets (>60% of energy intake) • Several diseases (type 2 diabetes, chronic renal failure, nephrotic syndrome) • Certain drugs (corticosteroids, estrogens, retinoids, higher doses of beta-blockers) • Various genetic dyslipidemias

Elevated Triglycerides Non-HDL Cholesterol: Secondary Target • Primary target of therapy: LDL cholesterol • Achieve LDL goal before treating non-HDL cholesterol • Therapeutic approaches to elevated non-HDL cholesterol

Non-HDL Cholesterol • Secondary target of therapy when serum triglycerides are 200 mg/d. L (esp. 200– 499 mg/d. L) • Non-HDL cholesterol = VLDL + LDL cholesterol = (Total Cholesterol – HDL cholesterol • Non-HDL cholesterol goal: LDL-cholesterol goal + 30 mg/d. L)

Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals for Three Risk Categories LDL-C Goal (mg/d. L) Non-HDL-C Goal (mg/d. L) CHD and CHD Risk Equivalent (10 -year risk for CHD >20% <100 <130 Multiple (2+) Risk Factors and 10 -year risk <20% <130 <160 <190 Risk Category 0– 1 Risk Factor

Specific Dyslipidemias: Causes of Low HDL Cholesterol (<40 mg/d. L) • • • Elevated triglycerides Overweight and obesity Physical inactivity Type 2 diabetes Cigarette smoking Very high carbohydrate intakes (>60% energy) • Certain drugs (beta-blockers, anabolic steroids, progestational agents)

Risk Can Vary Considerably with Same TC • • TC: 200 mg/d. L HDL: 25 mg/d. L LDL: 160 mg/d. L TG: 75 mg/d. L • • TC: 200 mg/d. L HDL: 70 mg/d. L LDL: 100 mg/d. L TG: 150 mg/d. L

Risk Can Vary Considerably with Same TC • • • TC: 200 mg/d. L HDL: 25 mg/d. L LDL: 160 mg/d. L TG: 75 mg/d. L This person would be at high risk for CHD based on lipid profile • • • TC: 200 mg/d. L HDL: 70 mg/d. L LDL: 100 mg/d. L TG: 150 mg/d. L This person would be at low risk for CHD based on lipid profile

Risk Can Vary Considerably with Same TC • • • TC: 200 mg/d. L LDL-C: 120 mg/d. L HDL-C: 30 mg/d. L TG: 450 mg/d. L 42 y. o. man, smoker What is his LDL goal?

Risk Can Vary Considerably with Same TC • • TC: 200 mg/d. L LDL-C: 120 mg/d. L HDL-C: 30 mg/d. L TG: 450 mg/d. L 42 y. o. man, smoker What is his LDL goal? A: he has 3 risk factors (male, smoker, low HDL), non-CAD, so his LDL goal is 130 mg/d. L

Risk Can Vary Considerably with Same TC • • • TC: 200 mg/d. L LDL-C: 120 mg/d. L HDL-C: 30 mg/d. L TG: 450 mg/d. L If TG are >200 mg/d. L, determine non-HDL cholesterol • TC – HDL = 170 mg/d. L • What is his goal?

Risk Can Vary Considerably with Same TC • • TC: 200 mg/d. L LDL-C: 120 mg/d. L HDL-C: 30 mg/d. L TG: 450 mg/d. L Non-HDL-C goal is LDL goal + 30 Patient has 2+ risk factors so goal is <130 mg/d. L Non-HDL goal is 160 mg/d. L

Blood Urea Nitrogen • Normal value: 10 -20 mg/dl • High: prerenal causes (CHF), renal obstruction, excessive intake of protein, GI bleeding, catabolic state, dehydration, glucocorticoid therapy; not specific to renal disease, though most renal diseases cause BUN • Low: inadequate dietary protein, severe liver failure

Creatinine • Normal value: 0. 7 -1. 2 mg/d. L • Breakdown product of creatine, an important component of muscle • Production depends on muscle mass, which varies very little. • Excreted exclusively by the kidneys • Level in the blood is proportional to the glomerular filtration rate. • A more sensitive test of kidney function than BUN because kidney impairment is almost the only cause of elevated creatinine.

Creatinine • Rising creatinine may indicate impending renal failure • Abnormal values appear late in chronic renal failure • Baseline creatinine will be low if patient muscle mass is low • Rise of 0. 3 to 0. 5 mg/d. L/day is a clinically significant rise

BUN to Creatinine Ratio • Normal range 10 -20: 1 • In kidney disease, the BUN: creatinine ratio is usually normal • Increased BUN to creatinine ratio is commonly caused by intravascular depletion (sodium, water and urea are retained by the body; creatinine is excreted)

BUN to Creatinine Ratio • High BUN: creatinine ratio may also be caused by protein loads in PN or EN; usually does not exceed 30 mg/d. L • Can also be caused by renal obstruction (e. g. kidney stones), poor renal perfusion or acute renal failure; medications including diuretics, corticosteroids, • Very high levels may be caused by GI or respiratory bleeding

Dehydration • Excessive loss of free water • Loss of fluids causes an increase in the concentration of solutes in the blood (increased osmolality) • Water shifts out of the cells into the blood • Causes: prolonged fever, watery diarrhea, failure to respond to thirst, highly concentrated feedings, including TF

Assessment of Hydration Status Physical Signs of Underhydration • Input < output over time • Decreased weight • Sunken, dry eyes • Dark-colored urine; oliguria • Dry mucous membranes • Sticky saliva • Poor skin turgor • Cool, pale, clammy skin

Assessment of Hydration Status Laboratory Signs of Underhydration • • Elevated sodium Elevated chloride Elevated BUN Elevated creatinine Elevated hemoglobin Elevated hematocrit Elevated serum osmolality • Elevated urine specific gravity

Laboratory Values and Hydration Status Lab Test Hypovolemia Hypervolemia BUN Normal: 10 -20 mg/dl Decreases Low: inadequate dietary protein, severe liver failure High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy Creatinine will also rise in severe hypovolemia Increases Other factors influencing result Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Laboratory Values and Hydration Status Lab Test BUN: creatinine ratio Normal: 10 -15: 1 Hypovolemia Increases Hypervolemia Decreases Other factors influencing result Low: inadequate dietary protein, severe liver failure High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Laboratory Values and Hydration Status Lab Test Hypovolemia Hypervolemia Other factors influencing result Hematocrit Normal: Male: 42 -52% Female: 37 -47% Increases Decreases Low: anemia, hemorrhage with subsequent hemodilution (occurring after approximately 12 -24 hours) High: chronic hypoxia (chronic pulmonary disease, living at high altitude, heavy smoking, recent transfusion) Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Laboratory Values and Hydration Status Lab Test Hypovolemia Hypervolemia Other factors influencing result Serum albumin Low: malnutrition; acute phase response, liver failure High: rare except in hemoconcentration Serum sodium Typical- , normal ly or can be normal or Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Laboratory Values and Hydration Status Lab Test normal Hypovolemia Hypervolemia Serum osmolality (285 -295 mosm/kg) Typically but can be normal or Urine sp. Gravity 1. 003 -1. 030 Urine osmolality (200 -1200 mosm/kg) Other factors influencing result Low: diuresis, hyponatremia, sickle cell anemia High: SIADH, azotemia, Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Laboratory Values and Hydration Status Lab Test Hypovolemia Hypervolemia Other factors influencing result Serum albumin Low: malnutrition; acute phase response, liver failure High: rare except in hemoconcentration Serum sodium Typically can be normal or , normal or Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Treatment of Dehydration • Use hypotonic IV solutions such as D 5 W • Offer oral fluids • Rehydrate gradually

Lab Data in Refeeding Syndrome • Check potassium, • Correct low levels phosphorus, prior to initiation of magnesium prior to hypocaloric feeds initiation of feeding in (<BEE x 1) and high-risk individuals monitor daily until stable at full feeds • A rapid decline along with fluid retention, • At risk pts are those derangements of with anorexia nervosa, glucose metabolism is alcoholism, prolonged seen with refeeding IV hydration or fasting

Stool Studies: C. Difficile • C. difficile associated diarrhea, cramps, fever, leukocytosis usually occurs within 12 mos of antibiotic use • Cytotoxin B is the most specific assay (toxin in stool); may need to test several times • Treatment: metronidazole or oral vancomycin • Avoid antidiarrheals

Stool Studies: Fat Malabsorption • Sudan III stain: qualitative study, can use random stool sample; positive results are increased (2+) or markedly increased (3+); more reliable for moderate to severe steatorrhea • Fecal fat test: pt consumes 80 -100 g fat/day a 72 -H stool collection is made; <7 g fat/24 h stool collection is normal

Hemoglobin • Normal values vary with age and gender • Decreased in anemia states d/t iron deficiency, thalassemia, pernicious anemia, liver disease, hypothyroidism, hemorrhage, hemolytic anemia • Increased in polycythemia vera, CHF, COPD

RBC Indices • MCV: mean corpuscular volume • MCHC: mean corpuscular hemoglobin concentration • MCH: mean corpuscular hemoglobin • Used to characterize anemias

MCV • Relates to the size of the average red blood cell • Macrocytic anemias: MCV 100 -150 f. L • Microcytic anemia: MCV<82 f. L • Normal: 82 -100 f. L • Helps identify cause of anemias, e. g. macrocytic may be due to B 12 or folic acid deficiency; microcytic may be iron deficiency or hemorrhage

MCHC • Average concentration of Hb in the red blood cells • Decreased in hypochromic anemias due to – Iron deficiency – Chronic blood loss – Some thalassemias

MCH • Mean weight of Hb per RBC • Helps in diagnosing severely anemic patients • Decrease: associated with microcytic anemia • Increase: in macrocytic anemias and newborns

RDW • Red cell size distribution width • Indication of abnormal variation in the size of RBCs • Can distinguish anemia of chronic disease (low MCV, normal RDW) from early iron-deficiency anemia (low MCV, high RDW) • Increased RDW in iron deficiency, B 12 or folate deficiency, hemolytic anemia • Normal in ACD, acute blood loss, aplastic anemia, sickle cell

Iron Deficiency Anemia vs Anemia of Chronic Disease Lab Index Iron. Deficiency Normal Anemia Serum Decreases Ferritin Men 12 -300 ng/m. L Women 10150 ng/m. L Serum iron Men 80 -180 ug, d. L Women 60160 ug, d. L Decreases Anemia Interpretation Chronic Disease Normal or Serum ferritin reflects increases total-body iron stores. Low ferritin is diagnostic of iron deficiency Decreases Serum iron is the amount of iron in the blood bound to transferrin and available for RBC production

Iron Deficiency Anemia vs Anemia of Chronic Disease Lab Index Iron. Deficiency Normal Anemia Total Iron Increases Binding Capacity Anemia Chronic Disease Decreases or lownormal 250 -460 ug/d. L Red Cell Increases Distributi on Width 11%-14. 5% Normal Interpretation Transferrin receptors available for iron binding; transferrin a negative acute phase respondent RDW rises early in iron deficiency; remains normal or nearly in ACD

Iron Deficiency Anemia vs Anemia of Chronic Disease Lab Index Iron. Deficiency Normal Anemia Mean Decreases Corpuscular Volume 80 -95 f. L Anemia Chronic Disease Usually normal Interpretation MCV measures the average size of RBCs. Normal in early iron deficiency, then falls as anemia progresses. But reduced levels seen in 15%-25% of patients with ACD

Dx of B-12 and Folate Deficiencies Lab Indices B-12 Folate Interpretation Deficiency Normal MCV Increases 80 -95 f. L Serum B-12 Decreases Usually 160 -950 pg/m. L normal High MCV also seen in alcoholism, liver disease, hypothyroidism, meds. Anemia more likely if MCV markedly Interpretation difficult; blood levels maintained at expense of tissue stores; 1/3 of persons with folate deficiency have low serum B 12 levels

Dx of B-12 and Folate Deficiencies Lab Indices B-12 Folate Interpretation Deficiency Normal Serum methylmalonic acid (MMA) Increases Normal MMA is specific for B-12 deficiency; however also seen in dehydration or renal disease. Test availability is limited 73 -271 mmol/L RBC folate Normal or Decreases RBC folate reflects folate adequacy during the 150 -450 ng/m. L decreases previous 1 -3 mos. However levels also reduced in ~50% of pts with B-12 deficiency, since uptake of folate depends on B-12

Dx of B-12 and Folate Deficiencies Lab Indices B-12 Folate Interpretation Normal Deficiency Serum folate Normal or Decreases Measurement of serum folate may be misleading; increases levels fluctuate with recent dietary intake; low folate in plasma and RBCs is strong indicator of deficiency 5 -25 ng/m. L Serum homocysteine 4 -14 mmol/L Increases greatly Increases moderatel y Increased levels are seen in folate, B-12, and B-6 deficiency; less frequently in renal insufficiency, hypothyroidism, inherited disorders

Diabetic Ketoacidosis (DKA) vs Hyperosmolar Hyperglycemic State (HHS) • DKA is seen most frequently in type 1 diabetes • HHS is seen most frequently in type 2 diabetes • Ketosis is also seen in alcoholism, starvation, very low carbohydrate diets, and up to 30% of first morning urine samples during pregnancy

Diabetic Ketoacidosis vs Hyperosmolar, Hyperglycemic State Hyperglycemia Diabetic Ketoacidosis Hyperosmolar, Hyperglycemic State Plasma glucose >250 mg/d. L Plasma glucose >600 mg/d. L Ketosis (ketones in Positive (plasma urine or blood) ketones ++++) Metabolic acidosis Arterial p. H< 7. 25 -7. 3 Serum bicarbonate low ( 15 -18 < m. Eq/L) Small (plasma ketones +/-) p. H>7. 3 Serum bicarbonate normal to slightly low (>15 m. Eq/L)

Diabetic Ketoacidosis vs Hyperosmolar, Hyperglycemic State Diabetic Ketoacidosis Electrolyte abnormalities Dehydration with serum osmolality Hyperosmolar, Hyperglycemic State Serum K+ is Normal serum K+ initially normal to ; then rapidly with correction of acidosis; insulin tx; volume expansion Variable >320 m. Osm/kg water

PTT and INR • Prothrombin is a protein produced by the liver for the clotting of blood • Depends on adequate Vitamin K intake and absorption • Prothrombin time is the time it takes to convert prothrombin to thrombin • INR means International Normalized Ratio • It is a ratio of the patient’s PT to that of International Reference Thromboplastin

PTT and INR • Are used often to evaluate the effectiveness of anticoagulant therapy with drugs such as heparin or coumarin • It is critical to stabilize INR so that the patient doesn’t clot or hemorrhage • High INR means more anticoagulation and greater risk of bleeding; low INR means higher risk of clotting • INR target is usually 2. 0 to 3. 0 depending on patient condition

Factors that Interfere with INR • Ingestion of excessive leafy green vegetables (vitamin K), promoting more rapid blood clotting (low INR) • Alcoholism prolongs clotting (high INR) • Diarrhea and vomiting prolongs clotting (high INR) • Technique of blood draw

Factors that Interfere with INR • Medications: antibiotics, aspirin, cimetidine, isoniazid, plenothiazides, cephalosporins, cholestyramines, phenylbutazone, metronidazole, oral hypoglycemics, phenytoin • Prolonged storage of plasma