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52 PART I PATIENTEVALUATION
N
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Na
K
Figure 4-2. Demonstrates method of recording values in the patient chart. This charting method allows universal communication within the patient progress notes.
Cl Na Cl
CO
BUN
Gluc
2
Cr
or
K
CO
2
BU
Cr
Gluc
Box 4-2. Common Causes of Basic Electrolyte Disturbances
Increase Decrease
Sodium (Na) Dehydration Diuretics
Potassium (K) Factitious (sample hemolysis,
Chloride (cl) Dehydration
Carbon dioxide (CO2) Dehydration Metabolic acidosis
Glycosuria CHF
Diabetes insipidus Renal failure
Cushing’s syndrome Vomiting
Excessivesweating Diarrhea
probably most common cause)
Dehydration
Renal failure
Acidosis
Addison’s disease
Iatrogenic
Metabolic acidosis (nonanion gap)
Diarrhea
Diabetes insipidus
Medications
Aldosterone deficiency
Respiratory acidosis Respiratory alkalosis
Vomiting Renal failure
Emphysema Diarrhea
Metabolic alkalosis Starvation
Liverfailure
Nephrotic syndrome
SIADH
Hypothyroidism
Pancreatitis
Hyperlipidemia
Multiple myeloma
Hyperglycemia—corrected
Na=1.6x1/100gglucoseover100g/dL
Diuretics
Nasogastric suctioning
Alkalosis
Mineral corticoid excess
Zollinger-Ellisonsyndrome
Vomiting
Excessivesweating
CHF
Chronic renal failure
Diuretics
DKA
SIADH
Aldosterone excess
CHF, Congestive heart failure; DKA, diabetic ketoacidosis; SIADH, syndrome of inappropriate secretion of diuretic hormone.
26. What are common causes of basic electrolyte disturbances (Box 4-2)?
27. What tests are used as markers for liver function or disease?
Serumalbumin,totalprotein,bilirubin,aspartateaminotransferase(AST=SGOT),alanineamino-
transferase(ALT=SGPT),alkalinephosphatase(ALP),gamma-glutamyltransferase(GGT),lactate
dehydrogenase(LDH),PT,bileacids,andbloodammonia.
28. How is the synthetic function of the liver evaluated?
Serumlevelsofalbumin,totalprotein,PT,bileacids,conjugatedbilirubin,BUN,andammoniaare
used to examine liver function. Although not widely used, the most sensitive test for liver or bile tract
CHAPTER 4 LABORATORYTESTS 53
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abnormality is for bile acids. Bile acids are water-soluble compounds produced from cholesterol
metabolism in the liver. Bile acid tests are best done 2 hours after eating and will show abnormalities in inactive cirrhosis and resolving hepatitis when other tests are normal. A more commonly
used liver function test is albumin level, which is decreased with liver damage as well as starvation,
inammatoryboweldisease,nephroticsyndrome,leukemia,andhemorrhageorburns.Albuminis
produced almost exclusively by the liver and makes up almost 75% of the total protein in serum, so
these tests usually parallel each other. Prothrombin is synthesized by the liver using vitamin K and will
be abnormal in severe, most often end-stage, and chronic liver disease. The absence of conjugated
bilirubin in the blood with severely elevated unconjugated bilirubin could indicate severely decreased
liver function. The ammonia level is used to diagnose and follow hepatic encephalopathy when failure
of the liver is already known.
29. What is the clinical significance of liver enzymes?
Anyincreaseofhepaticenzymesindicatescellulardamage.ASTismadeintheliver,heart,skeletal
muscle, and RBCs, so elevations may be due to liver disease, acute myocardial infarction (AMI), pancreatitis, muscle trauma, hemolysis, congestive heart failure (CHF), surgery, burns, or renal infarction.
IncreasedspecicityforliverdamageoccurswithelevationofALT,GGT,or5′-nucleotidase.ALPisfound
inlivercells,bileductepithelium,andosteoblasts.Therefore,elevationsofALPshouldbeconrmedto
involvetheliverorbileductsbycheckingaliverspecicfraction(GGT,ALT,or5′-nucleotidase level).
These tests will help rule out bone diseases, bone growth, healing of fractures, pregnancy, or childhood
physiologyasthecauseofALPelevation.Last,LDHisalsoincreasedinlivercelldamagewiththeLDH5
subfractionshowingaboutthesamesensitivityandsomewhatgreaterspecicityasAST.
30. What are the causes of bilirubin abnormalities?
Bilirubin is produced by the breakdown of hemoglobin in the reticuloendothelial system. This newly
formed bilirubin (indirect or unconjugated) circulates through the bloodstream bound to albumin. Hepatocytes extract the bilirubin and convert it to a water-soluble pigment via a process called conjugation;
thepigment,calleddirectorconjugatedbilirubin,issubsequentlyexcretedinbile.Elevationsoftotal
bilirubin in the blood cause jaundice (yellowing of skin and sclera, and pruritus) and may be caused by
bileobstructionorexcessivehemolysis.Elevationofunconjugatedbilirubinoccurswithobstructionand
hepatocellular disease, hemolytic anemia, and physiologically in newborns. The conjugated bilirubin
increasesprimarilywithobstructiontobileowandshouldbeassociatedwithanincreaseinALP.
31. What are common lab trends in liver disorders (Table 4-2)?
32. What tests monitor calcium (Ca) in the body?
Ca is the fourth most common extracellular cation and plays a vital role in membrane permeability.
The metabolically active Ca in the body is the ionized Ca2+ portion, which represents approximately
50%oftotalserumCa.Therangethatisconsiderednormalcoversonly0.44mg/dL,anindication
of its physiologic importance. The other half of serum Ca is bound by albumin (45%) and complexed
withanions.TotalCalevelwillbeloweredbydecreasesinalbuminsuchthatforeach1mg/dLdropof
albumin,Cawilldecreaseby0.8mg/dL.Thatis,correctedtotalCa=0.8×(normalalbumin–measured
albumin) + measured Ca. Possible causes of hypercalcemia include hyperparathyroidism, Paget’s
disease, metastatic bone tumor, hyperthyroidism, hypervitaminosis D, multiple myeloma, osteoporosis,
immobilization, thiazide drugs, and parathyroid-secreting tumors (lung, breast). Causes of hypocalcemia
include hypoparathyroidism (commonly after thyroid surgery), insufficient vitamin D, chronic renal failure,
hypomagnesemia, seizures, acute pancreatitis, and inaccurate reading as a result of hypoalbuminemia.
33. What two body elements are commonly linked to Ca metabolism?
Magnesium (Mg) and phosphorus (P) play important nutritional roles in the body and are associated
with Ca metabolism (Box4-3). Mg is the second most abundant intracellular cation and is found
mostlyinmuscle,softtissues,andbones(50%).Lessthan5%ofMgcirculatesintheblood,and
30%ofthisisboundtoalbumin.P,themostcommonintracellularanion,isusedinterchangeablywith
phosphate because much of the body’s store is as the anion compound. About 80% to 85% of P is
found in bones and 10% in muscle.
34. What blood tests are used to follow renal function?
BUN(normal:6to20mg/dL)andcreatinine(normal:0.7to1.4mg/dL)bloodlevelsaretheproducts
of protein and muscle metabolism, respectively, that are excreted by the kidneys. Decreased levels of
creatininearerarelysignicant,whereasdropsinBUNmaybeduetoliverfailure(siteofureaproduction),starvation,proteindeciency,over-hydration,nephroticsyndrome,orlatepregnancy.Elevations
Table 4-2. Lab Trends in Liver Disorders
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AST ALT ALP BILIRUBIN TOTAL CONJUGATED UNCONJUGATED GGT
Acute viral hepatitis ↑↑↑↑ ↑↑↑↑ ↑ ↑ varies ↑↑ ↑ ↑-↑ ↑↑↑
Chronic-resolving
hepatitis
Cirrhosis (active) ↑↑↑ ↑↑ ↑ N-↑ — — ↑↑ ↑↑↑
Cirrhosis (inactive) N-↑ N-↑ N-↑ N-↑ — — N-↑ ↑↑↑
ETOHhepatitis ↑↑↑ ↑-↑↑ ↑ N-↑ — — ↑↑↑ ↑↑
Obstruction
(intrahepatic)
Obstruction
(extrahepatic)
Metastatic disease N N ↑↑ ±↑ — — ↑↑ ↑↑
ETOH, Ethyl alcohol.
N-↑ N-↑ N-↑ N — — N-↑ ↑↑
↑↑ N-↑↑ ↑↑-↑↑↑ ↑↑ ↑↑ ↑↑ ↑↑↑ ↑↑↑
N-↑ N-↑ ↑↑↑ ↑↑↑ ↑↑↑ N-↑ ↑↑↑ ↑↑
54 PART I PATIENTEVALUATION
BILE
ACID
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Box 4-3. Common Causes of Calcium Metabolism Abnormalities
Increased Levels Decreased Levels
Magnesium (Mg) Renal failure Alcoholism
Phosphorus (P) Hypoparathyroidism Hyperparathyroidism
DKA, Diabetic ketoacidosis.
Mg antacid overdose Malnutrition
Specimenhemolysis Severediarrhea
DKA Hypercalcemia
Lithiumintoxication Hemodialysis
Hypothyroidism Loop/thiazidediuretics
Hypoalbuminemia
Nasogastric suction
Pancreatitis
Acidosis compensation
Chronic renal failure Alcoholism
Bone diseases Vitamin D deficiency
Healing fracture Glucose or insulin administration
Childhood Hypomagnesemia
Hemolysis Diuretics
Antacids
Nasogastric suction
Alkalosis
Hypokalemia
Gram-negative sepsis
of these compounds indicate severely decreased glomerular or tubular function. This can be the
result of reduced blood volume to kidneys (dehydration, shock, and pump failure), increased protein
intake, or catabolism. It can also be the result of direct parenchymal damage (glomerulonephritis,
chronic pyelonephritis, acute tubular necrosis, and acute glomerular damage) or obstruction of urine
ow(stones,strictures,tumor).Theseetiologiesareoftengroupedasprerenal,renal,andpostrenal,
respectively,andmayberesponsible,separatelyorincombination,forelevationsoftheBUNor
creatinine.
35. Are there more sensitive indicators of kidney dysfunction?
Yes.Urineclearanceofcreatinine,specicgravity,osmolality,electrolyteexcretion,andfreewater
clearance are tests used to evaluate kidney function. Clearance studies are most sensitive at defining
mild-to-moderate, diffuse glomerular disease by providing an estimate of glomerular filtration rate
(GFR). Creatinine is most often used because it estimates GFR with approximately 90% accuracy,
whereas urea only approximates to 60%. These studies are very difficult to perform because they
require a 24-hour collection, and all urine needs to be obtained accurately. In addition, the creati-
nineclearancemustbecorrectedforvariationinmusclemass,age,andsex.Urinespecicgravity
and osmolality tests measure the renal tubules’ ability to concentrate urine and involve protracted
preparation and collection times. All the above tests give more sensitive information regarding both
glomerularandtubularfunctionthanBUNorcreatinine;however,allaremoreexpensiveanddifcult
to obtain.
36. What information is obtained from a urinalysis?
• pH(4.5to8.0):Provideslittleusefulinformation
• Specific gravity(1.001to1.035):Thisprovidesaspotviewofkidneytubuleconcentrating
ability.
• Osmolality(500to1200mOsm/L):Itprovidessimilarinformationasspecicgravity.
• Blood or hemoglobin: Results may indicate stone, trauma, tumor, infection, or menstruation.
• Glucose/acetone: Positive results may indicate diabetes mellitus, pancreatitis, tubular disease, or
shock.
• Bilirubin: Normal is negative; positive results may indicate hepatitis or obstructive jaundice.
• Protein: Normal is negative; positive results might indicate fever, hypertension, glomerulonephritis,
nephrotic syndrome, myeloma, or heavy exercise.
56 PART I PATIENTEVALUATION
HCO
−
3
HCO
−
3
HCO
−
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• Nitrite: Normal is negative; positive results indicate infection.
• Leukocyte esterase: Normal is negative; positive results indicate infection.
• Ketones: Normal is negative; positive results may indicate starvation, diabetic ketoacidosis (DKA),
vomiting, diarrhea, or pregnancy.
• Microscopic:
• Squamousepithelialcells:Normalisnone;anymayindicatecontamination.
• RBC:Normalisnone;anymayindicatetumor,stone,orpyelonephritis.
• WBC:Count<5/hpfindicatesinfection.
• Castsindicatetubularkidneydiseaseorcrystals/stones.
37. What lab studies are used to evaluate the pancreas?
Because the production of enzymes in the pancreas is vital for digestion and maintenance of homeo-
stasis, the effects of pancreatic disease are seen in many tests. However, serum levels of amylase
(starch digestion), lipase (fat digestion), and trypsin (protein digestion) allow a direct indication of
pancreatic cell damage. Amylase levels peak about 29 hours after the onset of acute pancreatitis, as
does lipase; however, once active cell damage has stopped, the amylase returns to normal within
72 hours, whereas lipase does not normalize for 7 to 10 days. Amylase levels also may be elevated
because of common bile duct lithiasis, cholecystitis, tumor, peritonitis, peptic ulcer, intraabdominal
hemorrhage, intestinal obstruction or infarction, acute salivary gland disease, DKA, pregnancy, burns,
andrenalfailure.Lipaseshowsanincreasedspecicitytothepancreasbecauselipaselevelsare
elevated in pancreatitis, pancreatic duct obstruction, renal failure, and, much less significantly, intestinal
obstruction or infarction and cholangitis. Trypsin is the most pancreatic-specific exocrine enzyme,
butthisassayisnotwidelyavailable.Last,Calevelsalsoarefollowedinacutepancreatitisbecause
calcium levels decrease with lipase’s digestion of peritoneal fat (fat necrosis), which can provide
prognostic information.
38. How is blood glucose regulation monitored by the lab?
Glucose is regulated primarily by the liver in response to hormones released from structures such as
thepancreas(insulin,glucagon),adrenalmedulla(epinephrine),andadrenalcortex(cortisol/cortisone).
Blood glucose is used most commonly to diagnose diabetes mellitus and to explain altered mental
status.Afastinglevelabove140mg/dLornon-fastingglucose>200mg/dLisindicativeofdiabetes.A
glucose tolerance test provides a more accurate assessment of the patient’s ability to process glucose
but may be inaccurate in cases of fever, stress, afternoon testing, inactivity, advancing age, trauma,
or MI. Glycosylated hemoglobin or HgbA1c is used to monitor patient compliance and treatment
effectiveness and should be below 5.7%. An HgbA1c level above 6.5% indicates diabetes. The amount
of Hgb glycosylated is a function of degree and duration of RBC exposure to glucose and illustrates
average blood glucose over a 2- to 4-month period.
An increase in glucose levels may indicate diabetes mellitus (type I or II), acute pancreatitis,
hyperthyroidism, Cushing’s syndrome, acromegaly, epinephrine (e.g., exogenous, pheochromo, stress,
burn), advancing age, or sample drawn above intravenous access.
A decrease in glucose levels may indicate oral hypoglycemics or exogenous insulin, pancreatitis,
starvation, liver disease, sepsis, hypothyroidism, or postprandial reactive hypoglycemia (after gastric
surgery).
39. What is measured by a blood gas?
This test is conducted by drawing blood from an artery (usually radial or femoral) and then sending the
sample to the lab in ice with the patient’s temperature and current oxygen supplementation recorded
(Table4-3). Blood gas tests are used to determine the carbon dioxide and oxygen concentrations in
the blood and can therefore be used to measure the pH of blood.
40. What components of the blood gas are used in determining acid–base status?
The essential test values are the pH, PCO2,
metabolicformulawithanormalvalueof8to12mEq/L.Themajorbufferingsystemofthebloodis
bicarbonate-carbonic acid with the normal
The lungs are the major regulator of PCO2 with an increase of 10 mm Hg in hypoventilation
correspondingtoapHdropof0.08U.Thekidneyregulates[
abnormalities, but is much slower than the lungs and takes 1 to 2 days for correction. Hemoglobin
accounts for 75% of nonbicarbonate-based buffering of blood, while phosphate and other extracellular
proteins account for the rest.
, base difference, and anion gap (AG) from a basic
/CO2=20.
]withresponsetoacid–base
CHAPTER 4 LABORATORYTESTS 57
HCO
−
3
HCO
−
3
HCO
−
3
HCO
−
3
HCO
−
3
HCO
−
3
HCO
−
3
HCO
−
3
HCO
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Table 4-3. Blood Gas Measurements
DEFINITION NORMAL RANGE
pH Negative logarithm of hydrogen ion
7.35-7.45
concentration
PCO
2
Partial pressure of CO2 gas in blood
that is proportional to the amount
of dissolved CO
2
34-45mmHg
Concentration of bicarbonate in serum 20-28mEq/L
Base difference or
excess/decit
The normal base amount is calculated
using measured Hgb and normal
values for pH and
, then this
+2-2
is compared with measured amount
of blood base
PO
2
Blood oxygen tension or dissolved O2
content of plasma
80-95 mm Hg
If patient is younger than age
60, the lower limit is dropped
1mmHg/yearuntilage60is
reached
%SaO
2
Hgb, Hemoglobin.
Amount of Hgb bound with O2 compared
with the amount of Hgb available
Shouldbe>90%
41. How are acid–base abnormalities determined and classified?
ThefirststepistoevaluatepH.IfpH<7.35,thenthefindingisacidosis.ApH>7.45indicates
alkalosis. Any pH changes beyond 6.8 to 7.8 are incompatible with life. The next step uses
PCO2 and
to classify the primary abnormality as respiratory or metabolic, respectively.
Metabolic acidosis is then further classified as an AG or nonanion gap problem. There will be a
response to the primary disturbance by the opposite component in an attempt to compensate
or normalize the pH. If the blood gas does not match the calculated compensation, then a mixed
acid–basedisordershouldbesuspected;thatis,arespiratoryacidosisandmetabolicacidosis
occurring simultaneously.
42. What are the common causes and compensations in the primary acid–base
disorders?
• Respiratoryacidosis(hypoventilation):PCO2>45mmHg;
or4×DPCO2/10(chronic2to5days).Possibleetiology:chronicobstructivepulmonarydisease
(COPD), asthma, cardiac arrest, severe pulmonary edema or pneumonia, injury to airway or chest
wall, cerebrovascular accident (CVA), drugs (narcotics, sedatives), foreign body, muscular dystrophy,
or myasthenia gravis.
• Respiratoryalkalosis(hyperventilation):PCO2<35mmHg;
5×DPCO2/10(chronic).Possibleetiology:anxiety,pain,fever,pulmonaryembolus,mechanical
overventilation, head injury, hypoxia, increased altitude, interstitial lung disease, pregnancy, hyperthyroidism, hepatic insufficiency, aspirin overdose, or early sepsis.
• Metabolicacidosis:
<20mEq/L;PCO2decrease=8+(1.5×
• AGnormal:diarrhea,stula,renaltubularacidosis
• AGincreased=extraacid
• Exogenous:aspirin,methanol,ethyleneglycol,ETOHketoacidosis,hyperalimentation
• Endogenous:lacticacidosis,DKAorstarvationketoacidosis,uremia,severedehydration
• Metabolicalkalosis:
>28mEq/L,CO2increase=0.6×D[
tric suction, vomiting, diuretics, cystic fibrosis, posthypercapnia, Cushing’s syndrome, hyperaldosteronism, exogenous steroids, or hypoparathyroidism.
increase=changePCO2/10(acute)
decrease=2×DPCO2/10(acute),
).Possibleetiology:
].Possibleetiology:nasogas-
58 PART I PATIENTEVALUATION
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43. What components of the blood gas evaluate oxygenation?
The PO2and%SaO2 are used to monitor oxygenation. The PO2 gives an estimate of the alveolar gas
exchange with inspired air, so that the patient likely has normal ventilation if the PO2 is normal. The
amountofoxygenavailabletocellsisgivenbythe%SaO2, which may also be obtained using pulse
oximetry. The pulse ox has been shown to measure Hgb O2 saturation accurately between 70% and
100%, or PO2>35to40mmHg.Theoxygensaturationisinuencedbytemperature,pH,levelof
2,3-diphosphoglycerate(2,3-DPG),andPO2 as seen on the sigmoid-shaped O2 dissociation curve.
Hgb’s affinity for O2isdecreasedbyacidosis,fever,elevated2,3-DPG,andhypoxia,whichcausesa
shiftofthecurvetotheright,andisincreasedwithalkalosis,hypothermia,decreased2,3-DPG,and
banked blood, which causes a shift to the left.
44. How is an AMI ruled in or ruled out by the lab?
Much like the liver and pancreas, the heart has enzymes and proteins that are released from its cells
in damage or death. A single measure alone of these substances is not adequate to rule out an AMI,
and they should be checked at least twice in a 12-hour timeframe.
AST (SGOT) is found to increase in 90% to 95% of AMIs, begins elevation in 8 to 12 hours, peaks
at1to2days,andisnormalin3to8days.Thereisaroughcorrelationbetweendegreeofelevation
and extent of damage to the heart but low specificity for heart muscle.
LDHlevelsareelevatedin92%to95%ofAMIswithslightlyincreasedsensitivityoverAST.LDH
beginstoriseat24to48hours,peaksat2to3days,andisnormalat5to10days.Fractionatingof
isoenzymesshowsimprovedspecicity.LDH1/LDH2>1isseenin80%to85%ofAMIs.LDH1isfound
in RBCs, the heart, and the kidney, and normal values at 24 and 48 hours effectively rule out AMI.
Creatine kinase (CK)isincreasedin90%to93%ofAMIs.Levelsbegintorisein3to6hours,
peak at 12 to 24 hours, and are normal in 1 to 2 days. Fractionated isozymes are MM (skeletal muscle,
94%to100%oftotal),BB(brainandlung,usually0%oftotal),andMB(heartfraction,usually<6%of
total) and allow greater test specificity. There is a rough correlation with size of increase and amount
ofheartinfarcted.Levelsareusuallycheckedat0,12,and24hoursor0,8,16,and24hours.
Troponin-T is an antibody that detects the cardiac-specific regulatory proteins. It has approximately the same specificity and sensitivity as CK-MB but rises in 4 to 6 hours, peaks at 11 hours, and
is normal in 4 days.
Troponin-I is the same as troponin-T, but its timing is different; it begins to rise after 4 to
6 hours, peaks at 10 to 24 hours, and is normal after 10 days or more.
45. What tests are used to evaluate possible collagen vascular diseases?
Severalnonspeciclabtestsareusedtohelpdiagnosetheseenigmaticdiseases:
• Rheumatoid factor: Positive in collagen vascular diseases, rheumatoid arthritis (RA), systemic
lupuserythematosus(SLE),Sjögren’ssyndrome,scleroderma,polyarteritisnodosa,infections,CHF,
inammation,subacutebacterialendocarditis,MI,andlungdisease
• Lupus erythematosus (LE) preparation:Nocells=normal;positiveinSLE,RA,scleroderma,and
drug-induced lupus
• Antinuclear antibody (ANA):Negativeresult=normal;positiveinSLE,scleroderma,drug-induced
lupus, mixed connective tissue disease, RA, polymyositis, and juvenile RA
• Antimicrosomal: Detects Hashimoto thyroiditis
• Anticentromere: Tests for scleroderma, Raynaud disease, calcinosis, Raynaud phenomenon,
esophagealinvolvement,sclerodactyly,andtelangiectasia(CREST)syndrome
• Anti-SCL 70: Detects scleroderma
• Anti-DNA:DetectsSLE,mononucleosis,chronicactivehepatitis.
46. What are C-reactive protein (C-RP) and erythrocyte sedimentation rate (ESR) tests
used to evaluate?
TheC-RPandESRarenonspecificbutverysensitivemarkersforinfectionsandinflammatory
diseases.TheESRmeasureschangesinplasmaproteins(mainlyfibrinogen)andisevaluated
usingseveralscales(zetasedimentationratio,Wintrobemethod,Westergrenmethod).TheESR
is increased by any infection, inflammation, rheumatic fever, endocarditis, neoplasm, or AMI.
The C-RP is a glycoprotein produced by acute inflammation and tissue destruction. Its levels are
noted to begin elevating 4-6 hours after onset of inflammation and should be normal 5-7 days
postoperativelyoratleastdecreasingbyday3aftersurgery;otherwise,aninfectionislikely.
Other than inflammation or infection, the C-RP is also increased by pregnancy, oral contraceptives, and malignancies.
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47. What tests are used to screen for thyroid disease?
Themostsensitivescreeningtestforthyroiddiseaseisthethyroidstimulatinghormone(TSH)level,
which is elevated in hypothyroidism and low in hyperthyroidism. The thyroxine total (T4 Tot) screens
for hyperthyroidism with 95% sensitivity but is less accurate for hypothyroidism. Triiodothyronine
(T3)resinuptake(RU)isanindirectmeasurementofT4.Thetestmeasurestheproteinthyroid-
binding sites that are unbound and is elevated in hyperthyroidism, as a result of low thyroid-binding
globulin (TBG), or if the patient is taking medications that bind TBG (e.g., phenytoin, aspirin, steroids,
heparin).TheT3RUis80%sensitiveforhyperthyroidismbutonly40%forhypothyroidism.Thefree
thyroxineindex(FTI)isdeterminedbymultiplyingtheT4TotbytheT3RUandhasa95%sensitiv-
ity for hyperthyroidism and 90% to 95% sensitivity for hypothyroidism. The FTI attempts to balance
the TBG effects on T4 measurement. TBG is elevated in pregnancy, estrogen use, liver disease, and
hypothyroidism.TotalserumT3(T3-RIA)isalsomeasuredinsomelabsandisequivalenttoT4Tot
measurements.
48. What tests can be used to evaluate possible bone disease?
The Ca and P levels (discussed previously). Alkaline phosphatase also can be used and is elevated in
hyperparathyroidism, Paget’s disease, osteoblastic bone tumors, osteomalacia, rickets, pregnancy,
childhood, healing fractures, hyperthyroidism, and liver disease. The liver disorders may be ruled out
using fractionated enzyme levels or checking GGT or 5′-nucleotidase.
49. What procedures are done to evaluate body fluids and pathology specimens for
organisms?
The most definitive test to isolate infectious agents is culturing, but this requires 24 hours at minimum.
Stainingallowsforrapidscreeningidenticationtoassistinselectingempiricantibiotics.Themost
commonstainsare:
• Gram: Positive organisms turn a violet color because the microorganisms’ thick cell walls of
peptidoglycan and teichoic acid resist decolorization. Negative organisms have a thin cell wall
and outer lipoprotein or lipopolysaccharide coat that decolorize in alcohol and pick up the
counterstain (red).
• Acid-fast: These organisms do not decolorize in strong acid and are usually Mycobacterium
species.
• Potassium hydroxide (KOH): 10% KOH dissolves most cellular elements except for fungus
species.
• Wayson:Usedforgeneralbacteriascreening
• India ink:Identiesmostlyfungiincerebrospinaluid(CSF)
• Giemsa:Stainsintracellularorganisms(Chlamydia, malaria) and viral inclusion bodies
• NewertechnologywithDNA/polymerasechainreaction(PCR)probesandenzyme-linkedimmuno-
sorbentassay(ELISA)testsallowsrapiddetectionoforganisms(e.g.,Gonozyme,Streptozyme)or
monospot tests
50. What tests are used to evaluate viral hepatitis?
Hepatitis A:Oral/fecalhepatitisisusuallyself-limited.Acuteinfectiontestspositiveforimmuno-
globulin M (IgM) ± IgG. Old infection or convalescence tests negative for IgM but positive for IgG. The
antigen may be detected in stool but usually is gone before symptoms appear.
Hepatitis B: Blood-borne disease with 1% acute fatality; 5% to 15% develop chronic disease,
and3%develophepatocellularcarcinoma:
• HBsAg:SurfaceantigenfromviralouterenvelopeindicatescurrentoractivehepatitisBvirus(HBV)
infection; DNA PCR probe is most accurate indicator of activity, infectivity, and progression to
chronicity.
• Anti-HBs:ThisindicatesimmunityandendofacuteHBV.
• Anti-HBcAg(presenceofantibodytocoreviralprotein):Indicatesarecentoracuteinfection
andispresentduringcorewindowwhileHBsAgandanti-HBsarenegative;dropsoutafter3
to 6 months.
• Anti-HBcTot:Stayspositiveforlife;showsoldinfectionifHBsAgandHBc-IgMarenegative.
• HBeAg/Anti-HBe:Indicateinfectivity,becauseasanti-HBeincreases,theinfectivitydecreases.
• ChronichepatitisBstates:
• Carrier-positiveHBsAgbutnegativebiopsyandliverfunctiontests(LFTs)
• PersistenthepatitisB:Asabove,withnegativebiopsyandabnormalLFTs
• ActivehepatitisB:Asabove,withpositivebiopsyandabnormalLFTs
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Hepatitis C: Post-transfusion transmission; low severity acutely but 60% for chronic disease.
Hepatitis C virus (HCV) nucleic probe shows current infection, but this is still investigational, and antiHC indicates current, convalescing, or old HCV infection.
Hepatitis D: Requires HBV infection to be present, parenteral transmission, 5% acute fatality, 5%
chronic. HDAg indicates infection; may follow with antibody levels.
51. What tests are used to detect and monitor HIV infection?
HIV antigen detection is used by blood banks because they may detect viral presence as early as 1
to 2 weeks. Antibodies are used to detect core proteins p24 or p55 and envelope glycoproteins gp41,
120, or 160. They are about 80% to 90% sensitive if patients have symptoms but 60% to 65% with-
out.NucleicacidprobewithPCRamplicationisalsobeingusedwith98%sensitivityat3monthsbut
40% to 60% at 1 to 2 weeks. More commonly, patients are screened for the presence of antibodies in
theirserum,whichtakeanaverageof6to10weekstodeveloporseroconvert.TheELISAtestscreens
thepatient’sbloodforantibodies.ApositiveELISAtestisconrmedbyWesternblot,whichlooksfor
the most specific antibodies to gp41 and p24 or group-specific antigen (gag) core protein. Once HIV
infection is determined, the CD4 T-cell count, viral load, and beta-2-microglobulin levels are followed
for infection severity, prognosis, and activity and to direct therapy. The CD4 count (normal 600 to
1600cells/mm3) is a useful indicator of immune system damage and ability to respond effectively to
pathogens.Immunesuppressionoccurswithcountsbelow500cells/mm3 denoting an advanced risk
of opportunistic infections and need for prophylactic antibiotics. Viral load assays appear to be the
best prognostic marker for a patient’s long-term clinical outcome and are used in conjunction with
CD4 counts to direct antiviral therapy. Beta-2-microglobulin is a soluble marker for immune system
activation and can be used to evaluate disease progression or exacerbation.
52. What tests screen for or assist in the diagnosis of cancer?
Alpha-fetoprotein (AFP):Elevatedinhepatocellularcarcinoma,testiculartumors,occasionallybenign
hepaticdisease(hepatitis,alcoholiccirrhosis)andinpregnancy:neuraltubedefects,multiplegesta-
tion, or fetal death.
Cancer antigen 19-9 (CA 19-9):Elevatedin80%to85%pancreaticadenocarcinoma,40%to
50%gastricadenocarcinoma,30%to40%colorectalcancer,50%hepatocellularcarcinoma,16%to
20% lung cancer, and 14% to 27% breast cancer.
CA 125:Increasedinovarian,endometrial,andcoloncancers;alsoinendometriosis,inammatoryboweldisease,pelvicinammatorydisease,pregnancy,breastlesion,andteratomas.
Carcinoembryonic antigen (CEA): Not used to screen but is a good monitor of recurrence and
responsetotreatment(ifcheckedbeforestarted).Elevatedincolon,pancreas,lung,andstomachcancers, as well as in smokers and those with Crohn’s disease, liver disease, and ulcerative colitis.
Prostate specific antigen (PSA):Goodforscreeningandmonitoringaftertreatment.Levels
above10mg/dLareassociatedwithcancer>90%.Also,avelocityof0.75mg/mL/yearindicateshigh
suspicion for cancer. Differential diagnosis for elevation includes prostate cancer, acute prostatitis,
benign prostate hypertrophy, prostate surgery, and vigorous prostate massage. Normal rectal exam
hasnoinuence.
53. What basic tests are used to evaluate CSF?
Opening pressure: Normal is 100 to 200 mm Hg; most significantly elevated in bacterial infections
(meningitis)andsubarachnoidhemorrhage(SAH).
Color or appearance: Normal is clear and colorless, but bloody or xanthochromic (yellow from
Hgbbreakdown)after2to8hoursinSAHandwhiteorcloudyinbacterialinfections.
Glucose:Normalis0.5serumglucose(45to80mg/dL)butwillbe<20mg/dLinmeningitisand
between20and40mg/dLingranulomatousinfection(tuberculosisorfungal).
Protein:Normalrangeis15to45mg/dL,buttheupperlimitisdebated.Levelswillbe50to
1500mg/dLinmeningitisandwillbeincreasedbut<500mg/dLingranulomatousdisease.
Cell count:Normalisupto5/mm3 with all being lymphocytes; any condition that affects the
meningeswillcauseCSFleukocytosis,thedegreebeingdeterminedbytype,duration,andseverity
of irritation. The highest counts are seen in meningitis with PMNs dominating, whereas viral and
granulomatousdiseasecauseselevationsto10to500cells,withlymphocytespredominant.SAH
and traumatic taps will have increased cell counts made up of RBCs and WBCs in a ratio about equal
to blood (1 WBC per 500 to 1000 RBCs). However, no good formulas exist to confirm that the WBC
elevationisanartifactfromatraumatictapversusinfectiveorinammatoryincrease.Gramstainand
culture are performed in all suspected infective taps.
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54. What tests can be done to verify or exclude a CSF leak in craniofacial trauma?
ConrmationofCSFotorrheaorrhinorrheaintraumacanbechallenging.Typically,onelooksfora
colorlessuid,glucoseabout45mg/dL(nasalsecretions<30mg/dLandblood>80usually),andlow
protein and potassium compared with nasal secretions or serum. Trauma patients, however, often
exhibitacomplexmixtureofthesebodyuids,blockingchemicalanalysis.Themostsensitiveand
specictestrequiresabout2to10mLofuid,proteinelectrophoresis,andabout3hourstocomplete
in a modern lab. The beta-2-transferrin isozyme will be isolated correctly in the presence of any
mixtureofuid,andabeta-1subsetallowsreductionofcirrhoticfalse-positiveresults.Thistesthelps
preventtheneedformoreinvasiveradiologicstudiestoruleoutCSFleak.
55. Is a CBC of value in making a diagnosis?
Yes,butmostlyincertaindiagnoses.Forexample,iftheHctishigh(>45%),thepatientismostlikely
dehydratedormayhaveCOPD(emphysema).Ifitislow(<30%),thepatientmayhaveamorechronic
disease associated with blood loss.
Similarly,forWBCcount,ittakeshoursforinammationtoreleasecytokinesandcauseelevation
of the WBC count. Accordingly, a normal WBC count is not entirely inconsistent with infection.
56. How is urinalysis useful?
WBCs in the urine should direct attention to the diagnosis of pyelonephritis or cystitis, complications
of urinary tract infections. Hematuria may indicate renal or ureteral stones. RBCs and WBCs may be
found in the urine of patients with appendicitis.
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