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Solving Puzzles of Laboratory Data Interpretation

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Title: Solving Puzzles of Laboratory Data Interpretation


1
Solving Puzzles of Laboratory Data Interpretation
2
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

3
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 lt3.2 were predictive of risk
  • Kudsk et al, JPEN, 2003

4
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

5
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

6
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

7
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

8
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

9
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

10
CRP
  • Normal lt0.8 mg/dL (lt8 mg/L)
  • Rises within hours of an acute stimulus
  • Decrease in CRP of gt50 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

11
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)

12
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

13
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/dL
    or HDL lt40 mg/dL

14
Three Categories of Risk that Modify
LDL-Cholesterol Goals
  • Risk Category
  • CHD and CHD risk equivalents
  • Multiple (2) risk factors
  • Zero to one risk factor
  • LDL Goal (mg/dL)
  • lt100
  • lt130
  • lt160

15
Major Risk Factors for CHD
  • Cigarette smoking
  • Hypertension (BP gt140/90 mmHg or on
    antihypertensive medication)
  • Low HDL cholesterol (lt40 mg/dL)
  • Family history of premature CHD (CHD in male
    first degree relative lt55 years
  • CHD in female first degree relative lt65 years)
  • Age (men gt45 years women gt55 years)

16
CHD Risk Equivalents
  • Clinical CHD
  • Symptomatic carotid artery disease
  • Peripheral arterial disease
  • Abdominal aortic aneurysm.
  • Diabetes

17
ATP III Lipid and Lipoprotein Classification
  • LDL Cholesterol (mg/dL)
  • lt100 Optimal
  • 100129 Near optimal/above optimal
  • 130159 Borderline high
  • 160189 High
  • ?190 Very high

18
ATP III Lipid and Lipoprotein Classification
(continued)
  • HDL Cholesterol (mg/dL)
  • lt40 Low
  • ?60 High

19
ATP III Lipid and Lipoprotein Classification
(continued)
  • Total Cholesterol (mg/dL)
  • lt200 Desirable
  • 200239 Borderline high
  • ?240 High

20
Specific Dyslipidemias Elevated Triglycerides
  • Classification of Serum Triglycerides
  • Normal lt150 mg/dL
  • Borderline high 150199 mg/dL
  • High 200499 mg/dL
  • Very high ?500 mg/dL

21
Causes of High Triglycerides (?150 mg/dL)
  • Obesity and overweight
  • Physical inactivity
  • Cigarette smoking
  • Excess alcohol intake

22
Causes of High Triglycerides
  • High carbohydrate diets (gt60 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

23
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

24
Non-HDL Cholesterol
  • Secondary target of therapy when serum
    triglycerides are ?200 mg/dL (esp. 200499
    mg/dL)
  • Non-HDL cholesterol VLDL LDL cholesterol
    (Total Cholesterol HDL cholesterol
  • Non-HDL cholesterol goal LDL-cholesterol goal
    30 mg/dL)

25
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)
lt100
CHD and CHD Risk Equivalent (10-year risk for CHD
gt20
lt130
lt130
Multiple (2) Risk Factors and 10-year risk lt20
lt160
lt160
01 Risk Factor
lt190
26
Specific Dyslipidemias Causes of Low HDL
Cholesterol (lt40 mg/dL)
  • Elevated triglycerides
  • Overweight and obesity
  • Physical inactivity
  • Type 2 diabetes
  • Cigarette smoking
  • Very high carbohydrate intakes (gt60 energy)
  • Certain drugs (beta-blockers, anabolic steroids,
    progestational agents)

27
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

28
Risk Can Vary Considerably with Same TC
  • 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

29
Risk Can Vary Considerably with Same TC
  • 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?

30
Risk Can Vary Considerably with Same TC
  • 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

31
Risk Can Vary Considerably with Same TC
  • TC 200 mg/dL
  • LDL-C 120 mg/dL
  • HDL-C 30 mg/dL
  • TG 450 mg/dL
  • If TG are gt200 mg/dL, determine non-HDL
    cholesterol
  • TC HDL 170 mg/dL
  • What is his goal?

32
Risk Can Vary Considerably with Same TC
  • 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 lt130 mg/dL
  • Non-HDL goal is 160 mg/dL

33
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

34
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.

35
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

36
BUN to Creatinine Ratio
  • Normal range 10-201
  • In kidney disease, the BUNcreatinine 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)

37
BUN to Creatinine Ratio
  • High BUNcreatinine 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

38
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

39
Assessment of Hydration Status Physical Signs of
Underhydration
  • Input lt output over time
  • Decreased weight
  • Sunken, dry eyes
  • Dark-colored urine oliguria
  • Dry mucous membranes
  • Sticky saliva
  • Poor skin turgor
  • Cool, pale, clammy skin

40
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

41
Laboratory Values and Hydration Status
Adapted from Charney and Malone. ADA Pocket Guide
to Nutrition Assessment, 2004.
42
Laboratory Values and Hydration Status
Adapted from Charney and Malone. ADA Pocket Guide
to Nutrition Assessment, 2004.
43
Laboratory Values and Hydration Status
Adapted from Charney and Malone. ADA Pocket Guide
to Nutrition Assessment, 2004.
44
Laboratory Values and Hydration Status
Adapted from Charney and Malone. ADA Pocket Guide
to Nutrition Assessment, 2004.
45
Laboratory Values and Hydration Status
Adapted from Charney and Malone. ADA Pocket Guide
to Nutrition Assessment, 2004.
46
Laboratory Values and Hydration Status
Adapted from Charney and Malone. ADA Pocket Guide
to Nutrition Assessment, 2004.
47
Treatment of Dehydration
  • Use hypotonic IV solutions such as D5W
  • Offer oral fluids
  • Rehydrate gradually

48
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 (ltBEE x 1) and monitor daily
    until stable at full feeds
  • At risk pts are those with anorexia nervosa,
    alcoholism, prolonged IV hydration or fasting

49
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

50
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 lt7 g fat/24-h
    stool collection is normal

51
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

52
RBC Indices
  • MCV mean corpuscular volume
  • MCHC mean corpuscular hemoglobin concentration
  • MCH mean corpuscular hemoglobin
  • Used to characterize anemias

53
MCV
  • Relates to the size of the average red blood cell
  • Macrocytic anemias MCV 100-150 fL
  • Microcytic anemia MCVlt82 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

54
MCHC
  • Average concentration of Hb in the red blood
    cells
  • Decreased in hypochromic anemias due to
  • Iron deficiency
  • Chronic blood loss
  • Some thalassemias

55
MCH
  • Mean weight of Hb per RBC
  • Helps in diagnosing severely anemic patients
  • Decrease associated with microcytic anemia
  • Increase in macrocytic anemias and newborns

56
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

57
Iron Deficiency Anemia vs Anemia of Chronic
Disease
58
Iron Deficiency Anemia vs Anemia of Chronic
Disease
59
Iron Deficiency Anemia vs Anemia of Chronic
Disease
60
Dx of B-12 and Folate Deficiencies
61
Dx of B-12 and Folate Deficiencies
62
Dx of B-12 and Folate Deficiencies
63
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

64
Diabetic Ketoacidosis vs Hyperosmolar,
Hyperglycemic State
65
Diabetic Ketoacidosis vs Hyperosmolar,
Hyperglycemic State
66
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 patients PT to that of
    International Reference Thromboplastin

67
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 doesnt 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

68
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

69
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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