Clinical lab result interpretation-2

Dr. Bereket Molla Tigabu

 Glucose
Reference Range
normal Impaired Diabetic

Fasting 70-99mg/dL 100-125 mg/dL ≥126mg/dL

(3.5-5.5mmol/L) (5.6-6.9mmol/L) (>7mmol/L)

OGTT <140mg/dL 140-199mg/dL(7.9-11 ≥200mg/dL (>11.1

(<7.8mmol/L) .0mmol/L) mmol/L)

HbA1C 4%-5.6% 5.7%-6.4% ≥6.5%

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 Diagnostic criteria for DM
1. Symptoms of diabetes plus a random plasma glucose concentration ≥ 200 mg/dL
(11.1 mmol/L). The classic symptoms of diabetes include polyuria, polydipsia,
and unexplained weight loss. or

2. FPG ≥ 126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at
least 8 hours. or

3. Two-hour post-load glucose ≥ 200 mg/dL (11.1 mmol/L) during an OGTT. or

4. A1c ≥ 6.5%.

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 Oral glucose tolerance test
• A more standardized 2-hour glucose can be obtained by performing a
2-hour post-load glucose level when a patient is given a 75-g glucose
drink and a glucose level is drawn 2 hours later
• recommended for the diagnosis of gestational diabetes
• The patient should have fasted for 10 to 16 hours and the OGGT should be
performed in the morning because of diurnal variation of hormones
affecting glucose levels
• The drink containing 75 g of glucose should be consumed within 5
minutes, which should be timed when the patient begins to drink.
• Glucose levels are drawn fasting and at ½ hour, 1 hour, 2 hours, and 3
hour

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 Gestational DM (fasting 75g OGTT)

Time Plasma glucose One abnormal value is

Fasting ≥ 92 mg/dL (5.1 mmol/L) diagnostic of GDM
1 hour ≥ 180 mg/dL (10 mmol/L)
2 hour ≥ 153 mg/dL (8.5 mmol/L)

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 Glycosylated hemoglobin
•

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 Patient monitoring, ADA

HgA1C Fasting Post prandial Bedtime

Adult <7.0% 80-130mg/dL <180mg/dL (2
hour)
Adolescents <7.5% 90-130mg/dL 90-150mg/dL
and children
Pregnant <6.5% <95mg/dL 140mg/dL (1
women hour);
120mg/dL
(2hour)

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 Osmolality (Reference Range: 280–300 mOsm/kg or
mmol/kg)
•

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 Osmolality
• An increase in the measured serum osmolarity, relative to the calculated
osmolarity is osmol gap
• can be attributed to an increase in the number of solutes, a reduction in the
amount of free water (e.g., patients with significant dehydration), or
perhaps laboratory error

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 Case
• L.H. is a 45-year-old, overweight, woman with central obesity (height, 5
feet 5 inches; weight, 165 pounds; BMI, 27.5 kg/m2). She was referred to
the diabetes clinic when her gynecologist, who had been treating her for
recurrent monilial infections, noted glucosuria on routine urinalysis.
Subsequently, on two separate occasions she was found to have an FPG of
150 mg/dL and 167 mg/dL; an A1C was also checked and it was 8.2%.
L.H. denies any symptoms of polyphagia or polyuria, although lately she
has been more thirsty than usual. She does complain of lethargy and takes
afternoon naps when she can.
• Fasting laboratory assessment reveals glucose of 147 mg/dL, triglycerides
of 400 mg/dL, and an A1C of 8.3% (normal, 4%–6%). All other values
(including the complete blood count, electrolytes, LFTs, and renal
function tests) are within normal limits. L.H. is given the diagnosis of type
2 diabetes. What features in L.H.’s history and physical examination are
consistent with this diagnosis?

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 Cardiac markers (1)
• Cardiac biomarkers are useful for the evaluation, diagnosis, and
monitoring of patients in clinical practice
❑ Creatine Kinase, Reference Range: <150 units/L or <2.5 μkat/L
• catalyzes the transfer of high-energy phosphate groups in tissues that
consume large amounts of energy (e.g., skeletal muscle, myocardium,
brain).
• CK is composed of M and B subunits, which are further divided into three
isoenzymes: MM, BB, and MB.
• The CK-MM isoenzyme is found predominantly in skeletal muscle, the
CK-BB isoenzyme in the brain, and the CK-MB isoenzyme in the
myocardium.

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 Cardiac markers (2)
• Myocardial CK activity consists of 80% to 85% CK-MM and 15% to 20%
CK-MB.
• Non-cardiac tissues that contain large amounts of CK have either CK-MM
or CK-BB.
• The MB fraction is rare in tissues other than the myocardium
• CK-MB typically begins to increase 3 to 6 hours after an acute myocardial
infarction (MI), peaks at 12 to 24 hours, and accounts for about 5% or
more of the total CK
• if the amount of CK-MB exceeds 6% of the total, myocardial injury has
presumably occurred.

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 Case
• S.G., a 44-year-old woman, appears at the emergency department of a
local hospital, with complaints of sudden-onset chest pain, diaphoresis,
and nausea that began about 1 hour ago. S.G describes her pain as severe
and not relieved by position change, antacids, or nitroglycerin. An
electrocardiogram (ECG) reveals changes consistent with an acute MI.
The total CK serum concentration is 118 units/L and the CK-MB is 5
units/L. S.G. was admitted to the coronary care unit to rule out an acute
MI.
• Why are the total CK and CK-MB serum concentrations within the
reference range in S.G., despite clear evidence supporting an acute MI?

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 Troponin Reference, Range: <1.5
ng/mL or <1.5 mcg/L
• Troponins are proteins that regulate the calcium-mediated interaction of
actin and myosin within muscles.
• There are two cardiac-specific troponins, cardiac troponin I (cTnI) and
cardiac troponin T (cTnT).
• Whereas cTnT is present in cardiac and skeletal muscle cells, cTnI is
present only in cardiac muscle
• Compared with the detection of CK-MB, the presence of troponin I is a
more specific and sensitive indicator of myocardial damage

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 Troponin
• the concentration of cTnI increases
within 2 to 4 hours of an acute MI,
enabling clinicians to quickly
initiate appropriate therapy.
• Troponin also remains elevated for
about 10 days compared with the 2-
to 3-day elevation typically
observed with CK-MB.
• cTnI levels greater than 2.0 ng/mL
are suggestive of acute myocardial
tissue injury

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 Myoglobin, Reference Range: 0–90 mcg/L
• Myoglobin, a protein in heart and skeletal muscle cells,
• provides oxygen to working muscles. When muscle is damaged,
myoglobin is released into the bloodstream
• myoglobin concentrations in serum rise within 3 hours after insult to the
myocardial tissue, peak in about 8 to 12 hours, and return to normal in
about a day.
• less specific for myocardial tissue compared with CK-MB.
• Trauma or ischemic injury to non-cardiac tissue can increase serum
myoglobin.

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 Lactate Dehydrogenase
Reference Range: <200 units/L (adult)
• The enzyme lactate dehydrogenase (LDH) is present in the heart, kidney,
liver, and skeletal muscle. It is also abundantly present in erythrocytes and
lung tissue.
• Because increased serum concentrations of LDH can be associated with
diseases in many different organs and tissues, the diagnostic usefulness of
an LDH determination is somewhat limited

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 Brain Natriuretic Peptide
Reference Range: <100 pg/mL or <100
ng/L
• Brain natriuretic peptide (BNP) is released from the heart when increased
demands are placed on the myocardial tissue.
• Elevations in BNP are indicative of patients with congestive heart failure
(CHF).
• BNP counteracts the renin-angiotensin-aldosterone system and causes
vasodilatory effects, along with natriuresis (increased excretion of
sodium), all geared at reducing blood volume.
• Patients with some degree of CHF typically have BNP levels greater than
100 ng/L.
• BNP levels greater than 500 ng/L represent definite left ventricular
dysfunction

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 C-Reactive Protein
Reference Range: 0–1.6 mg/dL or 0–16
mg/L
• C-reactive protein (CRP) is a nonspecific, acute-phase reactant helpful in
the diagnosis and monitoring of inflammatory processes (e.g., rheumatoid
arthritis) and infections.
• CRP is produced by the liver in response to an inflammatory process.
• nonspecific test and does little to identify the cause or location of the
inflammation.
• more sensitive than ESR and is also associated with a more rapid and
greater response to acute inflammation
• hs-CRP or high-sensitivity CRP

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 CRP
• Risk assessment is stratified based on the following criteria:
• patients with hs-CRP values less than 1.0 mg/L have a low risk of cardiovascular
disease;
• patients with an hs-CRP between 1.0 and 3.0 mg/L correspond with average risk;
and
• patients with an hs-CRP greater than 3.0 mg/L are considered to be at high risk for
cardiovascular diseases.
• CRP has also been used to assess chronic inflammatory diseases such as
rheumatoid arthritis and Crohn’s disease
• viral infections do not typically increase CRP serum concentrations,
• the use of CRP as a diagnostic tool to differentiate viral versus bacterial infections

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 Lipid profile tests (1)
• Cholesterol, triglycerides, and phospholipids are the major lipids that
combine with proteins to be transported as complexes of lipid and proteins
known as lipoproteins.
• Lipids, such as cholesterol and triglycerides, are insoluble in plasma,
which is why the lipoproteins are required for transportation
❑ VLDL-C
• formed in the liver
• contain 15% to 20% of the total blood cholesterol concentration and most
of the total blood TG concentration.
• The concentration of cholesterol in these particles is approximately
one-fifth of the total TG concentration

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 Lipid profile tests (2)
• VLDL particles are large (thus limiting their ability to migrate into the
arterial wall) and appear to play only a small role in the pathogenesis of
atherosclerosis
❑ Very-low-density lipoprotein remnants/IDL-C
• The removal of TG by the action of the enzyme lipoprotein lipase (LPL)
makes the VLDL-C smaller and relatively more cholesterol rich.
• The particles formed through this process include small VLDL particles
(called remnant VLDL), intermediate-density lipoproteins (IDL), and LDL
• Approximately 50% of the remnant VLDL and IDL particles are removed
from the systemic circulation by receptors on the surface of the liver
(receptors called LDL or B-E receptors)
• the other 50% are converted into LDL particles.

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 Lipid profile tests (3)
❑ LOW-DENSITY LIPOPROTEINS (LDL-C)
• carry 60% to 70% of the total blood cholesterol and make the greatest
contribution to the development of atherosclerosis.
• Approximately half of may be taken up by peripheral cells or deposited in
the intimal space of coronary, carotid, and other peripheral arteries, where
atherosclerosis can develop.
• The probability that atherosclerosis will develop is directly related to the
concentration of LDL-C in the systemic circulation and the length of time
this level of exposure persists

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 Lipid profile tests (4)
❑ HIGH-DENSITY LIPOPROTEINS
• transport cholesterol from peripheral cells (i.e., lipid-rich inflammatory
cells in the arterial wall) back to the liver, a process called reverse
cholesterol transport
• Removes cholesterol from vascular tissue

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 Reference ranges
• •

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 Reference range
• HDL-Cholesterol • Triglycerides
• <40 mg/dL Low (men) • <150 mg/dL Normal
• <50 mg/dL low (women) • 150–199 mg/dL Borderline high
• ≥ 60mg/dL high • 200–499 mg/dL High
• >500 mg/dL Very high

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 Case-3 (1)
• T.A., a 43-year-old premenopausal woman, is screened with a lipid profile
during an annual medical evaluation. She has never taken
cholesterol-lowering medication and currently takes only a multivitamin
daily. She has had no symptoms of coronary, carotid, or peripheral
vascular disease. She has a 20–pack-year history of smoking and exercises
four times a week, without physical limitations. T.A. states that she
follows a low-fat, low-cholesterol diet. Her father is alive and well at age
71, with a normal cholesterol level. Her mother had an MI at age 47 and
died at age 57 from a second event. Her grandfather died of an MI at age
52; a sister has hypercholesterolemia and is taking simvastatin. Pertinent
physical findings are weight, 125 pounds; height, 63 inches; blood
pressure (BP), 120/82 mm Hg; pulse, 66 beats/minute and regular; carotid
pulses symmetric bilaterally without bruits; no neck masses; no abdominal
bruit; and no evidence of tendon xanthomas.

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 Case-3 (2)
• Pertinent laboratory findings, obtained after a 12-hour fast, show the
following results:
• Total cholesterol, 290 mg/dL
• TG, 55 mg/dL
• HDL-C, 55 mg/dL
• What is your assessment of T.A.’s lipid panel results?

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 Liver function tests-Bilirubin
• Bilirubin
• Total Bilirubin—Reference Range: 0.1–1.0 mg/dL or 1.7–17.1 μmol/L
Direct (Conjugated) Bilirubin—Reference Range: 0–0.2 mg/dL or 0–3.4
μmol/L
Jaundice: a condition characterized by yellow discoloration of the skin,
sclera, and mucous membranes
❖ Prehepatic Jaundice:
• Due to processes or diseases resulting in increased hemolysis and excessive
destruction of RBCs
• serum concentrations of indirect bilirubin increase.
• If the liver is conjugating and eliminating bilirubin normally, total bilirubin will
increase out of proportion to the direct bilirubin, and the other LFTs will appear
within the reference range

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 Bilirubin (2)
❖ Hepatic Jaundice :
• a disproportional increase of total bilirubin relative to the direct bilirubin (i.e., the
indirect bilirubin will be increased)
• Increase in liver enzymes
• Examples of other causes of hepatic jaundice are cirrhosis, viral hepatitis,
hepatocellular carcinoma, and alcoholic liver disease
❖ Posthepatic Jaundice :
• involve cholestatic or obstructive causes
• Blockage of the bile duct secondary to cholelithiasis (gallstone) or tumor
• increase conjugated (direct) bilirubin.
• mild elevations in AST and ALT, marked increases in ALP and GGT
• increased excretion of excess conjugated bilirubin in the urine commonly results in
dark brown–colored urine

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 Serum albumin (Reference Range:
3.6–5 g/dL or 36–50 g/L )
• Serum albumin levels are important in determining the chronicity and
severity of the liver disease.
• In acute liver disease, the albumin levels are often normal or within the
reference range.
• A decreased albumin is indicative of chronic liver disease, although it can
be present in severe, acute liver disease

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 Liver Enzymes (1)
• Liver enzymes play an important role in the assessment of liver function
because injury to the liver resulting in cytolysis or necrosis will cause the
release of enzymes into circulation.
• Enzymes also play an important role in differentiating hepatocellular
(functional) from obstructive (mechanical) liver disease
• aminotransferases (ALT and AST), the phosphatases (ALP and
5′-neucleotidase), GGT, and lactate dehydrogenase (LD)

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 Liver Enzymes (2)
❖ Aminotransferases
• AST (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (serum
glutamic pyruvic transaminase [SGPT])
• the serum activity of both transaminases rises rapidly in almost all
diseases of the liver and may remain elevated for up to 2 to 6 weeks.
• The highest levels of AST and ALT are found in acute conditions such as
viral hepatitis, drug- and toxin-induced liver necrosis, and hepatic
ischemia.

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 Liver Enzymes (3)

• The increase in ALT activity is usually greater than that for AST.
• Only moderate increases are found in less severe conditions.
• AST and ALT are found to be normal or only mildly elevated in cases of
obstructive liver damage.
❑ AST: Reference Range: 0–35 units/L or 0–0.58 µkat/L
• abundant in heart and liver tissue and moderately present in skeletal
muscle, kidney, and pancreas

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 Liver Enzymes (4)

• used to evaluate myocardial injury and to diagnose and assess the

prognosis of liver disease resulting from hepatocellular injury
❑ ALT: Reference Range: 0–35 units/L or 0–0.58 µkat/L
• elevations in serum ALT are more specific for liver-related injuries or
diseases.
• Evaluating the ratio of ALT to AST can be potentially useful, particularly
in the diagnosis of viral hepatitis

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 Case 4 (1)
• L.M., a 59-year-old woman currently taking atorvastatin 40 mg daily for
hypercholesterolemia, complains of fatigue and myalgia during the past
week since her last prescription refill. On assessment, her primary care
provider determines she has been taking an incorrect dose. Instead of
cutting an 80-mg tablet in half, she has been taking the entire tablet,
thereby effectively doubling her dose. The physician orders liver function
tests (LFTs), CK, and SCr to evaluate her myalgia. Laboratory results
indicate the following: AST, 51 units/L ALT, 72 units/L ALP, 82 units/L
CK, 216 units/L SCr, 1.4 mg/dL
• Why are these laboratory results of sufficient concern to warrant
discontinuation or dose reduction of atorvastatin?

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 Alkaline Phosphatase (Reference Range: 20–130 units/L or
0.33–2.17 µkat/L)
• The alkaline phosphatases (ALPs) constitute a large group of isoenzymes
that play important roles in the transport of sugar and phosphate.
• These isoenzymes of ALP have different physiochemical properties and
originate from different tissues (e.g., liver, bone, placenta, and intestine).
• In normal adults, ALP is derived primarily from liver and bone.
• this enzyme is secreted into the bile, and substantially elevated ALP serum
concentrations can be seen with mild intrahepatic or extra-hepatic biliary
obstruction.

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 ALP
• Thus, the presence of early bile duct abnormalities can result in elevated
ALP before increases in the serum bilirubin are observed.
• Drug-induced cholestatic jaundice (e.g., chlorpromazine or sulfonamides)
can increase serum ALP concentrations.

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 Gamma-Glutamyl Transferase (Reference Range: male 9–50
units/L, female 8–40 units/L )
• found in the kidney, liver, and pancreas
• its major clinical value is in the evaluation of hepatobiliary disease.
• An increase in the serum concentration of GGT parallels the increase of
ALP in obstructive jaundice and infiltrative disease of the liver.
• increased ALP in the presence of a normal GGT is more suggestive of
muscular or bone-related issues.
• GGT is a hepatic microsomal enzyme, tissue concentrations increase in
response to microsomal enzyme induction by alcohol and other drugs
(e.g., carbamazepine, phenobarbital, and phenytoin).

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 Case-5
• A.R., a 42-year-old man with a 2-year history of hypertension controlled
with hydrochlorothiazide and a 1-year history of Parkinson disease
controlled by carbidopa/levodopa, is hospitalized after an episode of
orthostatic hypotension. Admitting laboratory results show a hematocrit
(Hct) of 27%. Because A.R. had a long history of alcoholism, additional
laboratory tests were obtained. His results were as follows:
• Total bilirubin, 3.5 mg/dL Direct bilirubin, 0.5 mg/dL ALP, 40 units/L
AST, 32 units/L ALT, 27 units/L
• what might be the most logical cause of increased bilirubin in A.R.?

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