Transcript 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, ThyroxinBinding 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, LDLcholesterol, 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/dL or HDL <40 mg/dL
Three Categories of Risk that Modify
LDL-Cholesterol Goals
Risk Category
LDL Goal
(mg/dL)
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 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
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•
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Clinical CHD
Symptomatic carotid artery disease
Peripheral arterial disease
Abdominal aortic aneurysm.
Diabetes
ATP III Lipid and
Lipoprotein Classification
LDL Cholesterol (mg/dL)
<100
100–129
optimal
130–159
160–189
190
Optimal
Near optimal/above
Borderline high
High
Very high
ATP III Lipid and
Lipoprotein Classification (continued)
HDL Cholesterol (mg/dL)
<40
60
Low
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
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•
•
•
Normal
Borderline high
High
Very high
<150 mg/dL
150–199 mg/dL
200–499 mg/dL
500 mg/dL
Causes of High Triglycerides
(150 mg/dL)
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•
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)
Non-HDL-C
Goal (mg/dL)
CHD and CHD Risk Equivalent
(10-year risk for CHD >20%
<100
<130
Multiple (2+) Risk Factors and
10-year risk <20%
<130
<160
<160
<190
Risk Category
0–1 Risk Factor
Specific Dyslipidemias:
Causes of Low HDL Cholesterol (<40 mg/dL)
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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
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•
•
•
TC: 200 mg/dL
HDL: 70 mg/dL
LDL: 100 mg/dL
TG: 150 mg/dL
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
•
•
•
•
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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
Risk Can Vary Considerably
with Same TC
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•
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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?
Risk Can Vary Considerably
with Same TC
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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
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 >200 mg/dL, determine non-HDL
cholesterol
• TC – HDL = 170 mg/dL
• What is his goal?
Risk Can Vary Considerably
with Same TC
•
•
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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 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
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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
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
Hypovolemia
BUN:
Increases
creatinine
ratio
Normal:
10-15:1
Hypervolemia
Other factors
influencing result
Decreases
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 
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 D5W
• 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/24h 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 IronDeficiency
Normal
Anemia
Serum
Decreases
Ferritin
Men 12-300
ng/mL
Women 10150 ng/mL
Serum
iron
Men 80-180
ug,dL
Women 60160 ug,dL
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 IronDeficiency
Normal
Anemia
Total Iron Increases
Binding
Capacity
Anemia
Chronic
Disease
Decreases
or lownormal
250-460
ug/dL
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 IronDeficiency
Normal
Anemia
Mean
Decreases
Corpuscular
Volume
80-95 fL
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 Deficiency
Normal
MCV
Increases
Increases
80-95 fL
Serum B-12 Decreases Usually
160-950 pg/mL
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
B12 levels
Dx of B-12 and Folate Deficiencies
Lab Indices B-12
Folate
Interpretation
Deficiency 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/mL 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 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/mL
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
Diabetic
Ketoacidosis
Hyperglycemia
Plasma glucose
>250 mg/dL
Ketosis (ketones
Positive (plasma
in urine or blood) ketones ++++)
Metabolic acidosis Arterial pH<
7.25-7.3
Serum
bicarbonate low (
15-18 < mEq/L)
Hyperosmolar,
Hyperglycemic State
Plasma glucose >600
mg/dL
Small (plasma
ketones +/-)
pH>7.3
Serum bicarbonate
normal to slightly low
(>15 mEq/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 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