Solving Puzzles of Laboratory Data Interpretation

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/dL• 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/dL• 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/dL• 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/dL

• 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/dL (<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 GuidelinesNew 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/dL or HDL <40 mg/dL

Risk Category

CHD and CHD riskequivalents

Multiple (2+) risk factors

Zero to one risk factor

LDL Goal (mg/dL)

<100

<130

<160

Three Categories of Risk that Modify LDL-Cholesterol Goals

Major Risk Factors for CHD

• Cigarette smoking• Hypertension (BP >140/90 mmHg or on

antihypertensive medication)• Low HDL cholesterol (<40 mg/dL)• 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/dL)

<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/dL)

<40 Low

60 High

ATP III Lipid and Lipoprotein Classification (continued)

Total Cholesterol (mg/dL)

<200 Desirable

200–239 Borderline high

240 High

Specific Dyslipidemias: Elevated Triglycerides

Classification of Serum Triglycerides

• Normal <150 mg/dL

• Borderline high 150–199 mg/dL

• High 200–499 mg/dL

• Very high 500 mg/dL

Causes of High Triglycerides(150 mg/dL)

• 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/dL (esp. 200–499 mg/dL)

• Non-HDL cholesterol = VLDL + LDL cholesterol= (Total Cholesterol – HDL cholesterol

• Non-HDL cholesterol goal: LDL-cholesterol goal + 30 mg/dL)

Comparison of LDL Cholesterol and Non-HDL Cholesterol Goals for

Three Risk Categories

LDL-C Goal(mg/dL)Risk Category

Non-HDL-C Goal (mg/dL)

<100CHD and CHD Risk Equivalent(10-year risk for CHD >20%

<130

<130Multiple (2+) Risk Factors and10-year risk <20%

<160

<1600–1 Risk Factor <190

Specific Dyslipidemias: Causes of Low HDL Cholesterol (<40 mg/dL)

• 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/dL• HDL: 25 mg/dL• LDL: 160 mg/dL• TG: 75 mg/dL

• TC: 200 mg/dL• HDL: 70 mg/dL• LDL: 100 mg/dL• TG: 150 mg/dL


• TC: 200 mg/dL• HDL: 25 mg/dL• LDL: 160 mg/dL• TG: 75 mg/dL• This person would be

at high risk for CHD based on lipid profile

• TC: 200 mg/dL• HDL: 70 mg/dL• LDL: 100 mg/dL• TG: 150 mg/dL• This person would be

at low risk for CHD based on lipid profile


• TC: 200 mg/dL

• LDL-C: 120 mg/dL

• HDL-C: 30 mg/dL

• TG: 450 mg/dL

• 42 y.o. man, smoker

• What is his LDL goal?


• TC: 200 mg/dL• LDL-C: 120 mg/dL• HDL-C: 30 mg/dL• TG: 450 mg/dL• 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/dL


• TC: 200 mg/dL• LDL-C: 120 mg/dL• HDL-C: 30 mg/dL• TG: 450 mg/dL• If TG are >200 mg/dL, determine non-HDL

cholesterol• TC – HDL = 170 mg/dL• What is his goal?


• TC: 200 mg/dL• LDL-C: 120 mg/dL• HDL-C: 30 mg/dL• TG: 450 mg/dL• Non-HDL-C goal is LDL goal + 30• Patient has 2+ risk factors so goal is <130 mg/dL• Non-HDL goal is 160 mg/dL

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/dL• 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/dL/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/dL

• 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 StatusPhysical 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 StatusLaboratory 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 StatusLab Test Hypo-

volemiaHyper-volemia

Other factors influencing result

BUN

Normal: 10-20 mg/dl

Increases 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

Adapted from Charney and Malone. ADA Pocket Guide to Nutrition Assessment, 2004.

Laboratory Values and Hydration Status

Lab Test Hypo-volemia

Hyper-volemia


BUN: creatinine ratio

Normal: 10-15:1

Increases Decreases Low: inadequate dietary protein, severe liver failure

High: prerenal failure; excessive protein intake, GI bleeding, catabolic state; glucocorticoid therapy


Laboratory Values and Hydration StatusLab Test Hypo-

volemiaHyper-volemia


Hemato-crit

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)




Hyper-volemia


Serum albumin

Low: malnutrition; acute phase response, liver failure

High: rare except in hemoconcentration

Serum sodium

Typical-ly can be normal or

, normal or



Lab Test

normal

Hypo-volemia

Hyper-volemia


Serum osmolality

(285-295 mosm/kg)

Typically but can be normal or

Typically but can be normal or

Urine sp. Gravity

1.003-1.030

Urine osmolality (200-1200 mosm/kg)

Low: diuresis, hyponatremia, sickle cell anemia

High: SIADH, azotemia,




Hyper-volemia


Serum albumin

Low: malnutrition; acute phase response, liver failure

High: rare except in hemoconcentration

Serum sodium

Typically can be normal or

, normal or


Treatment of Dehydration

• Use hypotonic IV solutions such as D5W

• Offer oral fluids

• Rehydrate gradually

Lab Data in Refeeding Syndrome

• Check potassium, phosphorus, magnesium prior to initiation of feeding in high-risk individuals

• A rapid decline along with fluid retention, derangements of glucose metabolism is seen with refeeding

• Correct low levels prior to initiation of hypocaloric feeds (<BEE x 1) and monitor daily until stable at full feeds

• At risk pts are those with anorexia nervosa, alcoholism, prolonged IV hydration or fasting

Stool Studies: C. Difficile

• C. difficile associated diarrhea, cramps, fever, leukocytosis usually occurs within 1-2 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 fL• Microcytic anemia: MCV<82 fL• Normal: 82-100 fL• Helps identify cause of anemias, e.g.

macrocytic may be due to B12 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, B12 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

Normal

Iron-Deficiency Anemia

Anemia Chronic Disease

Interpretation

Serum FerritinMen 12-300 ng/mL

Women 10-150 ng/mL

Decreases Normal or increases

Serum ferritin reflects total-body iron stores. Low ferritin is diagnostic of iron deficiency

Serum ironMen 80-180 ug,dL

Women 60-160 ug,dL

Decreases Decreases Serum iron is the amount of iron in the blood bound to transferrin and available for RBC production


Lab Index

Normal



Interpretation

Total Iron Binding Capacity250-460 ug/dL

Increases Decreases or low-normal

Transferrin receptors available for iron binding; transferrin a negative acute phase respondent

Red Cell Distribution Width11%-14.5%

Increases Normal RDW rises early in iron deficiency; remains normal or nearly in ACD


Lab Index

Normal



Interpretation

Mean Corpus-cular Volume80-95 fL

Decreases Usually normal

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

Normal

B-12 Deficiency

Folate Deficiency

Interpretation

MCV80-95 fL

Increases Increases High MCV also seen in alcoholism, liver disease, hypothyroidism, meds. Anemia more likely if MCV markedly

Serum B-12160-950 pg/mL

Decreases Usually normal

Interpretation difficult; blood levels maintained at expense of tissue stores; 1/3 of persons with folate deficiency have low serum B12 levels


Lab Indices

Normal

B-12 Deficiency

Folate Deficiency

Interpretation

Serum methyl-malonic acid (MMA)73-271 mmol/L

Increases Normal MMA is specific for B-12 deficiency; however also seen in dehydration or renal disease. Test availability is limited

RBC folate150-450 ng/mL

Normal or decreases

Decreases RBC folate reflects folate adequacy during the previous 1-3 mos. However levels also reduced in ~50% of pts with B-12 deficiency, since uptake of folate depends on B-12


Lab IndicesNormal

B-12 Deficiency

Folate Deficiency

Interpretation

Serum folate 5-25 ng/mL

Normal or increases

Decreases Measurement of serum folate may be misleading; levels fluctuate with recent dietary intake; low folate in plasma and RBCs is strong indicator of deficiency

Serum homo-cysteine4-14 mmol/L

Increases greatly

Increases moderately

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

Diabetic Ketoacidosis

Hyperosmolar, Hyperglycemic State

Hyperglycemia Plasma glucose >250 mg/dL

Plasma glucose >600 mg/dL

Ketosis (ketones in urine or blood)

Positive (plasma ketones ++++)

Small (plasma ketones +/-)

Metabolic acidosis Arterial pH< 7.25-7.3

Serum bicarbonate low ( 15-18 < mEq/L)

pH>7.3

Serum bicarbonate normal to slightly low (>15 mEq/L)

Diabetic Ketoacidosis vs Hyperosmolar, Hyperglycemic State

Diabetic Ketoacidosis

Hyperosmolar, Hyperglycemic State

Electrolyte abnormalities

Serum K+ is initially normal to ; then rapidly with correction of acidosis; insulin tx; volume expansion

Normal serum K+

Dehydration with serum osmolality

Variable >320 mOsm/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

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Solving Puzzles of Laboratory Data Interpretation