Cardiovascular Diseases

Arrhythmias
Metabolic abnormali ties shoul d al ways be rul ed out before performing Hol ter monitor studies or commi tting to l ong-term anti arrhythmi c therapy (e.g., hypokal emia, hypomagnesemia, anemi a, hypoxemia, hypo- or hyperthyroi di sm).

Arteriovenous Fistulas, Angiomatous, Congenital

Pl atel et count may be decreased.

Behet's Syndrome
y

(Systemi c vasculitis involving arteries and vei ns characteri zed by tri ad of recurrent aphthous ul cers of mouth and genitalia, and rel apsing panuvei ti s.)

y y

No defi nitive laboratory tests Laboratory fi ndings due to involvement of vari ous organ systems, e.g.,
o

Large vessel occlusi on (e.g., aneurysms, arthri ti s, meningi tis) Skin lesi ons

Churg-Strauss Syndrome (Allergic Granulomatosis and Angiitis)

Bi opsy showing granul ocytes around an arteri ole and venul e establishes the diagnosi s.1

y y y

ESR i s hi gh. WBC count is increased. Eosinophilia is usual and seems to correl ate with disease acti vity.

y y

Serum IgE i s often increased. p-ANCA i s found in 60% of pati ents. c-ANCA i s rare.

Cor Pulmonale
y y

Secondary pol ycythemi a Increased bl ood CO 2 when cor pulmonal e i s secondary to chest deformiti es or pulmonary emphysema

Laboratory fi ndings of the primary lung disease (e.g., chroni c bronchiti s and emphysema, mul tiple small pul monary emboli , pul monary schistosomi asi s)

Coronary Heart Disease (CHD)

y

Increased ri sk factors
o

Increased serum total and LDL cholesterol , decreased HDL chol esterol and vari ous rati os (see Chapter 12).

Recent reports suggest that apo A-I and apo B may be better di scriminators of CHD than cholesterol , and l ow rati o of apo A-I to apo B may be best predi ctor. (Vari ati on i n methodol ogy and l ack of interl aboratory standardi zati on makes thi s di ffi cul t to eval uate at present.)

P.114

Atherogeni c i ndex (combinati on of rati o of LDL to HDL apo B wi th rati o of apo B to apo A-I) =

o o

Increased serum homocystei ne >15.9 mol/L (normal = 5-15 mol /L) tri pl es ri sk of AMI. Each increase of 5 mol/L increases ri sk equivalent to i ncreased cholesterol of 20 mg/dL. Increase may be due to vi tami n B defi ciency or geneti c defi ciency of methyl enetetrahydrofol ate reductase enzyme. Increased in endstage renal di sease dial ysis patients and in hypothyroi dism, certai n drug therapi es (e.g., methotrexate [transi ent], phenytoin and carbamazepine [mil d], theophylline, ni trous oxi de), ci garette smoki ng.

Low pl asma vitamin B 1 2 and fol ate level s are each independent ri sk factors for cor 717d36h onary artery di sease.

Increased serum tri gl yceri de level i s a ri sk factor but may not be independent of other factors.

Clinical evi dence of CHD or atherosclerosi s in patient <age 40, family history of premature CHD, hypertensi on, male gender, smoking.

Syndrome X: insulin resistance, l ow HDL level , hi gh level of very l ow density li poproteins (VLDLs) and tri glyceri des.

Vari ous abnormaliti es of bl ood cl otti ng mechani sms (e.g., fi brinogen, factor VII, antithrombi n III, phospholipi d anti bodi es, protei n C, protei n S).

Li poprotein el ectrophoresi s (see Tabl e 13-6) shows a specifi c abnormal pattern in <2% of Americans (usually types II, IV). Chi ef purpose of test is to i dentify rare familial di sorders (I, III, V) to antici pate problems i n children.

Li poprotein el ectrophoresi s may be i ndi cated if serum tri glyceri de level i s >300 mg/dL, fasti ng serum i s lipemi c, or hypergl ycemi a, si gnifi cant gl ycosuri a, i mpai red glucose tolerance, or increased serum uri c aci d (>8.5 mg/dL) i s present.

Perform l aboratory tests to rule out di abetes mellitus, liver di sease, nephroti c syndrome, dysproteinemias, hypothyroi dism.

Endocarditis, Bacterial
y

Bl ood culture i s positive in 80-90% of pati ents. Streptococcus vi ri dans causes 40-50% of cases; Staphyl ococcus aureus, 15-20%; Streptococcus pneumoniae, 5%; and Enterococcus, 5-10%. Other causes may be gramnegative bacteri a (~10% of cases; e.g., Escheri chia coli , Pseudomonas aerugi nosa, Kl ebsiella, Proteus) and fungi (e.g., Candi da, Hi stopl asma, Cryptococcus). Bartonell a has been reported to cause 3% of cases, whi ch may be culture negative.

In drug addi cts, S. aureus causes 50-60% of cases and ~80% of tri cuspi d infecti ons; gram-negative bacteri a cause 10-15% of cases; cases due to polymi crobi al and unusual organi sms appear to be increasing. 75% of pati ents may be HIV posi tive.

Proper bl ood cultures requi re adequate vol ume of bl ood, at least five cul tures taken duri ng a peri od of several days with temperature of 101F or more (preferabl y when hi ghest), anaerobi c as well as aerobi c growth, vari ety of enri ched medi a, prompt i ncubati on, prol onged observati on (growth i s usual i n 1-4 days but may requi re 2-3 wks). Beware of negative culture due to recent antibi otic therapy. Beware of transi ent bacteremia after dental procedures, tonsillectomy, etc., which does not represent bacteri al endocardi ti s (in these cases, streptococci usually grow only in flui d medi a; in bacteri al endocardi ti s, many col onies al so occur on soli d medi a). Bl ood culture is al so negative i n bacteri al endocarditi s due to Ri ckettsi a burnetii , but phase 1 complement fixati on test is posi tive.

Posi tive bl ood cultures may be more difficult to obtai n in prostheti c valve endocardi ti s (due to unusual and fasti di ous organi sms), ri ght-si ded endocarditi s, uremia, and l ongstandi ng endocardi tis. A singl e positi ve cul ture must be interpreted with extreme caution. Asi de from the excepti ons noted in thi s paragraph, the di agnosi s shoul d be based on two or more cultures posi tive for the same organi sm.

Serum bacteri ci dal test measures ability of seri al diluti ons of pati ent's serum to sterilize a standardi zed inoculum of pati ent's i nfecting organi sms; it i s someti mes useful to

demonstrate inadequate anti bi otic levels or to avoi d unnecessary drug toxici ty. P.115

Progressi ve normochromi c normocyti c anemi a i s a characteri sti c feature; in 10% of pati ents, Hb l evel i s <7 gm/dL. Rarely there i s a hemolytic anemi a wi th a positive Coombs' test. Serum i ron i s decreased. Bone marrow contai ns abundant hemosi deri n.

WBC i s normal in ~50% of patients and el evated 15,000/cu mm in the rest, wi th 65-86% neutrophils. Higher WBC indi cates presence of a compli cati on (e.g., cerebral , pul monary). Occasi onally l eukopeni a i s present. Monocytosi s may be pronounced. Large macrophages may occur i n peri pheral bl ood.

Pl atel et count i s usually normal , but occasi onally it i s decreased; rarely purpura occurs.

Serum proteins are al tered, with an increase in gamma gl obulin; therefore posi tive ESR and tests for cryogl obulins, RF, etc., are found. Often a di rect correl ati on i s seen between ESR and course and severity of di sease.

Hematuri a (usually mi croscopi c) occurs at some stage in many patients due to gl omeruliti s, renal infarct, or focal emboli c GN.

Al buminuri a i s almost i nvari ably present, even wi thout these complicati ons. Renal i nsuffi ciency with azotemia and fixed specifi c gravi ty is infrequent now.

y y

Nephroti c syndrome i s rare. CSF findings in vari ous complicati ons, meningi ti s, brai n abscess

Laboratory fi ndings due to underl ying or predi sposi ng di seases or complicati ons
o o o o o

Rheumati c heart di sease. Congeni tal heart disease. Infection of geni tourinary system. Congestive heart failure. Bacteri al endocarditi s occurs in 4% of pati ents wi th prostheti c valves.

Other.

Giant Cell Arteritis (GCA)

y y

(Systemi c panarteri tis of medi um-si zed el asti c arteri es) Bi opsy of involved segment of temporal artery is di agnosti c,1 but negati ve bi opsy does not exclude GCA because of skip lesi ons. Therefore, surgeon shoul d remove at least 20 mm of artery, paraffi n secti ons of which must be examined at multi ple levels. Bi opsy findings remai n posi tive for at least 7-14 days after onset of therapy.

Cl assi c tri ad of increased ESR (50 mm/hr),1 anemia, increased serum ALP i s strongly suggesti ve of GCA.

Mil d to moderate normocytic normochromi c anemi a i s present in 20-50% of cases and is rough indi cator of degree of inflammati on.

ESR i s markedl y increased in vi rtually all patients (97%); average Westergren = 107. A normal ESR excludes the

di agnosi s when little clini cal evi dence exi sts for temporal arteriti s. CRP test has equal sensitivi ty.
y y

Serum ALP i s slightl y increased in ~25% of patients. WBC i s usually normal or slightly increased with shift to the left.

y y

Pl atel et count may be nonspecifi cally i ncreased. Serum protein electrophoresi s may show increased gamma gl obulins. Rouleaux may occur.

y y

Serum CK i s normal . Laboratory fi ndings refl ect specific organ i nvol vement.
o o

Ki dney (e.g., GN). CNS (e.g., i ntracerebral artery invol vement, whi ch may cause increased CSF protein; stroke; mononeuriti s of brachi al plexus).

Heart and great vessel s (e.g., myocardi al i nfarcti on, aorti c di ssecti on, Raynaud's di sease).

o o o o

Mil d liver functi on abnormalities in 20-35% of patients. SIADH. Mi croangi opathi c hemol ytic anemia. Pol ymyal gia rheumati ca i s presenting symptom in onethi rd of patients and ulti mately devel ops in 50-90% of cases.

Heart Failure
y

Renal changes:
o

Sli ght al bumi nuri a (<1 gm/day) is common. P.116

Isol ated RBCs and WBCs, hyaline, and (sometimes) granul ar casts.

o o

Urine i s concentrated, with specifi c gravi ty >1.020. Phenol sulfonphthalein (PSP) excreti on and urea clearance are usually depressed.

Moderate azotemi a (BUN usually <60 mg/dL) i s evi dent with severe oli guri a; may increase wi th vi gorous diuresi s. (Pri mary renal di sease i s indi cated by proporti onate increase in serum creati nine and l ow specifi c gravi ty of urine despi te oliguri a.)

o y

Oli guri a i s a characteri sti c feature of ri ght-si ded failure.

ESR may be decreased because of decreased serum fi bri nogen.

Pl asma vol ume i s increased. Serum al bumin and total protein are decreased, with i ncreased gamma gl obulin. Hct is sli ghtly decreased, but RBC mass may be increased.

Pl asma sodi um and chl ori de tend to fall but may be normal before treatment. Uri ne sodi um i s decreased. Total body sodi um is markedly increased and potassium i s decreased. Pl asma potassium i s usually normal or sli ghtly increased (because of shi ft from intracellular l ocati on); it may be somewhat reduced wi th hypochl oremi c alkal osi s due to some diureti cs.

y y

Li ver functi on changes. Laboratory fi ndings due to underl ying di sease (e.g., rheumati c fever, vi ral myocardi ti s, bacteri al endocardi tis,

chroni c severe anemi a, hypertension, hyperthyroi di sm, Hurl er's syndrome).

o

Aci dosi s (reduced bl ood pH) occurs when renal insuffi ciency is associ ated or CO 2 retenti on exists due to pul monary insuffi ciency, l ow pl asma sodium, or ammonium chl ori de toxi city.

Alkal osi s (increased bl ood pH) occurs i n uncompli cated heart failure itself, in hyperventil ati on, in alveol arcapillary bl ock due to associ ated pul monary fibrosi s, after mercuri al diuresi s that causes hypochl oremi c alkal osi s, or because of potassium depleti on.

Alkal osi s (with normal or i ncreased bl ood pH) showing increased plasma bicarbonate and moderatel y increased pCO 2 after acute correcti on of respi ratory aci dosi s is due to CO 2 retenti on when there is chlori de defici t and usually decreased potassium.

Hypertension
y y

(Present i n 18% of adults in the Uni ted States) Systoli c hypertensi on

o o o

Hyperthyroi di sm Chroni c anemia with hemogl obi n <7 gm/dL Arteri ovenous fi stul as-advanced Paget's di sease of bone; pulmonary arteri ovenous varix

o y

Beri beri

Di astolic hypertensi on
o

Hypothyroi dism

Systoli c and diastoli c hypertensi on

Essential (pri mary) hypertensi on (causes >90% of cases of hypertensi on).

Secondary hypertensi on (causes <10% of cases of hypertensi on). Laboratory fi ndings due to the primary di sease. These condi ti ons are often unsuspected and shoul d always be ruled out, because many of them represent curabl e causes of hypertensi on.

Due To
y

Endocrine di seases
o

Adrenal


Pheochromocytoma (<0.64% of cases of hypertensi on)

   o

Al dosteronism (<1% of cases of hypertensi on) Cushing's syndrome Congeni tal adrenal hyperpl asia (CAH;)

Pituitary disease
 

Si gns of hyperadrenal functi on Acromegaly

o o y

Hyperthyroi di sm Hyperparathyroi dism

Renal di seases P.117

Vascul ar (4% of cases of hypertensi on)

Renal artery stenosi s (usually due to atheromatous pl aque in el derly patients and to fibromuscul ar hyperpl asi a in younger pati ents) (0.18% of cases of hypertensi on)

     o

Nephroscl erosi s Emboli sm Arteri ovenous fi stul a Aneurysm Aorti tis or coarctati on of aorta with renal i schemia

Parenchymal
      

Gl omerul onephri tis Pyel onephri ti s Pol ycysti c kidneys Ki mmel stiel-Wil son syndrome Amyl oi dosi s Collagen di seases Renin-produci ng renal tumor (Wilms' tumor; renal hemangi operi cytoma)

  y

Mi scellaneous Urinary tract obstructi ons

Central nervous system di seases

o o o

Cerebrovascul ar acci dent Brai n tumors Poli omyeliti s

Other
o o o

Toxemi a of pregnancy Pol ycythemia Acute porphyri a

Drugs, toxins

o o o

Oral contraceptives, tri cyclic anti depressants Lead, al cohol Li cori ce ingesti on

In children <18 yrs of age

Renal di sease

6178%

Cardi ovascul ar di sease (e.g., coarctati on of aorta)

1315%

Endocrine (e.g., mi neral ocorti coi d excess, pheochromocytoma, hyperthyroi di sm, hypercal cemia)

6-9%

Mi scellaneous (e.g., induced by tracti on, after GU tract surgery, associ ated with sleep apnea)

2-7%

Essential

116%

In neonates and young infants

o

Most common

Renal artery thrombosi s after umbilical artery catheteri zati on

   o

Coarctati on of aorta Congeni tal renal disease Renal artery stenosi s

Less common
  

Bronchopulmonary dyspl asi a Patent ductus arteri osus Intraventri cular hemorrhage

Laboratory fi ndings indi cati ng the functi onal renal status (e.g., uri nalysi s, BUN, creatinine, uri c aci d, serum el ectrol ytes, PSP, creati nine cl earance, radi oi sotope scan of ki dneys, renal bi opsy). The hi gher the uri c acid in uncompli cated essenti al hypertension, the l ess the renal bl ood fl ow and the hi gher the renal vascul ar resi stance.

Laboratory fi ndings due to complicati ons of hypertensi on (e.g., congestive heart failure, uremi a, cerebral hemorrhage, myocardi al infarcti on)

Laboratory fi ndings due to admini strati on of some anti hypertensive drugs

o

Oral diureti cs (e.g., benzothiadi azines)



Increased inci dence of hyperuri cemi a (to 65-75% of hypertensive patients from i ncidence of 25-35% in untreated hypertensive pati ents)

 

Hypokalemi a Hypergl ycemi a or aggravati on of preexi sting di abetes mellitus P.118

Less commonl y, bone marrow depressi on, aggravati on of renal or hepati c i nsuffici ency by el ectrol yte imbal ance, chol estati c hepatiti s, toxi c pancreati tis

Hydral azi ne


Long-term dosage of >200 mg/day may produce syndrome not di stingui shabl e from SLE. Usually regresses after drug is di sconti nued. Antinuclear anti body may be found in 50% of asymptomati c pati ents.

Methyldopa


20% of patients may have posi tive results on di rect Coombs' test, but relatively few have hemolyti c anemi a. When drug i s disconti nued, Coombs' test may remain positi ve for months but anemi a usually reverses promptly. Abnormal liver functi on tests indi cate hepatocellular damage without jaundi ce associ ated with febrile influenzalike syndrome. RA and SLE tests may occasi onally be posi tive (see Chapter 17). Rarely, granul ocytopeni a or thrombocytopeni a may occur.

Monoamine oxi dase i nhi bitors (e.g., pargyli ne hydrochl ori de)


Wi de range of toxic reacti ons, most seri ous of whi ch are

 

Bl ood dyscrasi as Hepatocellul ar necrosi s

Di azoxi de
 

Sodi um and flui d retenti on Hypergl ycemi a (usually mild and manageabl e by insulin or oral hypoglycemi c agents)

When hypertensi on i s associ ated with decreased serum potassium, rul e out
o o

Pri mary al dosteroni sm Pseudoal dosteroni sm (due to excessive i ngesti on of licori ce)

o o o o

Secondary al dosteroni sm (e.g., malignant hypertension) Hypokalemi a due to diuretic admini strati on Potassium l oss due to renal di sease Cushing's syndrome

Kawasaki Syndrome (Mucocutaneous Lymph Node Syndrome)

y

(Vari ant of chil dhood polyarteri tis of unknown eti ol ogy, with hi gh inci dence of cardi ac complicati ons; di agnosi s is based on clini cal cri teri a)

Di agnosi s i s confi rmed by histol ogi c examinati on of coronary artery (same as in poly- arteriti s nodosa).

y y

Laboratory changes due to acute myocardi al infarcti on Acute phase reactants are increased (e.g., ESR, CRP, alpha1-antitrypsin); usually return to normal after 6-8 wks.

Leukocytosi s (20,000-30,000/cu mm) with shift to left duri ng fi rst week; lymphocytosi s thereafter; peaks at end of second week; thi s is a hallmark of the illness.

Anemi a occurs in ~50% of patients; reaches nadi r about end of second week; improves duri ng recovery.

CSF shows increased mononucl ear cell s wi th normal protein and sugar.

y y

Increased mononuclear cells in urine; dipsti ck negative. Increased WBC(predomi nantly PMNs) in joi nt fl ui d in patients with arthriti s.

Lffler's Parietal Fibroplastic Endocarditis

y

Eosi nophilia 70%; may be absent at fi rst but appears sooner or l ater.

y y

WBC frequently increased. Laboratory fi ndings due to frequent

o

Mural thrombi in heart and emboli zati on of spl een and lung

Mitral and tri cuspi d regurgitati on

Myocardial Contusion
y y

(90% due to motor vehi cl e acci dent) Increased serum CK-MB (>3%) al one in 15% of cases; combined with ECG changes in 20% of cases; ECG changes al one in 65% of cases

Increased serum cardi ac troponi n I (cTnI) i mplies some myocardi al necrosi s and differenti ates increased CK-MB due to skeletal muscl e damage. Speci ficity = 90% but P.119

sensi tivity = only 30% and posi tive predi ctive value = only 16%. Cardi ac troponi n T (cTnT) may be i ncreased due to muscl e necrosi s.

Fi g. 5-1. Al gori thm for di agnosi s of acute myocardial infarcti on.

Myocardial Infarction, Acute (AMI)

y y

See Fi gs. 5-1 and 5-2 and Tables 5-1, 5-2 and 5-3. Incl udes the whol e spectrum of acute coronary syndromes, from silent i schemia, unstable angina, and "non-Q wave" infarcti on, to typical AMI.

Diagnostic Criteria for AMI

y

Two of the foll owing three findings:

o o

Hi story of i schemi c chest di scomfort for 30 mins Characteri stic evol uti on of ECG changes

Fi g. 5-2. Seri al serum cardi ac markers after acute myocardi al infarcti on.

o o

P.120

Typi cal ri se and fall of cardi ac enzymes. Bl ood shoul d be drawn promptl y after onset of symptoms. Repeat determinati ons should be made at appropri ate interval s (e.g., 4, 8, and 12 hrs) and also i f symptoms recur or new si gns or symptoms devel op. Changes may indi cate extensi on or addi ti onal myocardi al infarcti on (MI) or other complicati ons (e.g., pul monary i nfarcti on).

Use of Laboratory Determinations

For di agnosi s when ECG changes are nondi agnosti c (occurs i n ~50% of AMI patients) on admi ssi on to emergency room (e.g., masked by bundl e branch bl ock or Wol ff-Parkinson-White syndrome) or may not reveal intramural or posteri or or l ateral infarcts. Fal se-positive ECG occurs i n >10-20% of cases.

o o o

For differential diagnosi s of chest pain. To foll ow the course of the pati ent wi th AMI. To estimate prognosi s (e.g., marked el evati on of serum enzyme [4-5 normal] correl ates with i ncreased inci dence of ventri cul ar arrhythmi a, shock, and heart failure, and wi th hi gher mortality).

For noni nvasive assessment of coronary reperfusi on after thrombol yti c therapy.

Utility of each enzyme depends on ti me of speci men's collecti on after onset of AMI.

Combinati on of markers (e.g., serum myogl obi n, CK-MB, cTn) and (rati os of) seri al changes are most effecti ve because of uncertainty as to actual durati on of myocardi al damage.

Serum Total Creatine Kinase (CK)

y

Use
o

Repl aced by serum cTn, CK-MB, myogl obin in vari ous combinati ons.

May all ow early di agnosi s because increased level s appear 3-6 hrs after onset and persi st48 hrs.

Sensi tive i ndicator because of l arge amplitude of change (6-12 normal).

Interpretati on
o

Seri al total CK has sensi tivity of 98% early in course of MI but fal se-posi tive rate of 15% due to many causes of increased CK.

Returns to normal by thi rd day; a poorer prognosi s i s suggested if the increase l asts more than 3-4 days. Rei nfarcti on i s indi cated by an elevated level after the fi fth day after previ ous return to normal . P.121

Useful in di fferenti al di agnosi s of chest pain due to di seases often associ ated with MI or diffi cul t to di sti ngui sh from MI.

Table 5-1. Summary of Increased Serum Marker Level s After Acute Myocardi al Infarcti on (AMI)

Serial Serum CK-MB Concentrations

y

Use
o

Present gol d standard for di agnosis wi thi n 24 hrs of onset of symptoms.

Detect reinfarcti on or extensi on of MI after 72 hrs.

o y y

Document reperfusi on after thrombol yti c therapy.

Interpretati on . In AMI, CK-MB usually i s evi dent at 4-8 hrs, peaks at 1524 hrs (mean peak = 16 normal ), wi th sensi tivity and specifi city each >97% withi n the first 48 hrs. By 72 hrs, twothi rds of patients still show some increase in CK-MB. More frequent sampling (every 6 hrs) i s more likely to identify a peak val ue. False-negative results may be due to sampling ti ming (e.g., only once in 24 hrs or sampling <4 hrs or >72 hrs after AMI).

. Di agnosis of AMI i s usually confi rmed by 8-12 hrs, and sampli ng beyond 24 hrs is usually not needed except to detect earl y reinfarcti on (especi ally in patients receiving thrombolytic therapy).

. Di agnosis of AMI should not be based on only a single enzyme val ue. One cri teri on for AMI i s seri al CK-MB measurements 4 hrs apart that show 50% i ncrease with at least one sampl e greater than upper reference val ue. P.122

Table 5-2. Interpretati on of Markers for Diagnosi s of Acute Myocardi al Infarcti on (AMI)

Table 5-3. Characteri sti cs of Serum Markers for Myocardi al Damage

. In ~5% of AMI patients (especially i n ol der age groups) a peak CK-MB may be the onl y abnormali ty, with total CK and CK-MB still within reference ranges. Thi s i s because normal serum total CK values decline with decreased muscle mass (e.g., wi th age and sedentary or bedri dden status).

. Rapi d return to normal makes CK-MB a poor marker >72 hrs after symptoms.

. Increased CK-MB with normal total CK may i ndi cate non-Q wave AMI.

. MB index (CK-MB/total CK) shoul d be calcul ated; normal <2.5. For example, with extreme skel etal muscle injury (e.g., trauma, peri operative condi ti on), total CK may be >4000 U/L and CK-MB may be 40 U/L.

. CK-MB should be reported in units as well as percentage, because if i njury of both cardi ac and skeletal muscle (e.g., peri operative AMI) is present, CK-MB percentage may not appear i ncreased.

. CK-MB mass i mmunoassays (preferred method) at 0, 3, and 6 hrs can measure small but signi fi cant seri al changes that may still be withi n the normal range. CK-MB mass 10 g/L indi cates AMI. Serum CK-MB can now be measured di rectl y in the emergency room wi th or without total CK, cTn, and myogl obi n.

. Thrombolyti c therapy shoul d be given within 4-6 hrs of the acute event, at whi ch time CK-MB may not yet be increased.

CK-MB, cTn, and myogl obin measured i niti ally and at 60 and/or 90 mins after thrombol yti c therapy can document fail ed reperfusi on.2 P.123

60 min

90 min

Sens itivit y

Spec ificit y

Sens itivit y

Spec ificit y

CKMB

(1 .5 ) 33% 85%

( 5 ) 82% 66%

( (5 ) 93% 60% 1 0 ) 91% 49%

(1 cTnT .5 ) 70% 65%

( 5 ) 82% 67%

( (5 ) 97% 43% 1 0 ) 95% 58%

Myo gl obi n

(1 .5 ) 42% 89%

( 5 ) 84% 73%

( (5 ) 92% 59% 1 0 ) 88% 65%

Numbers in parentheses are rati os of marker values after thrombolytic therapy to pretreatment values.

CK and CK-MB May Also Be Increased In

y

Di agnostic value of CK-MB and total CK are dimini shed after cardi ac surgery. A di agnosi s of AMI cannot be made until

>12-24 hrs after cardi ac surgery; typi cally AMI patients have hi gher peak values of CK, CK-MB, and myogl obi n; patients without AMI have earlier peaks that return to base val ues more rapi dly.
y

Increases common after angi opl asty of coronary arteri es; may indi cate reperfusi on.

Cardi ac trauma and contusi ons, electri cal injury, and inflammatory myocardi ti s may produce enzyme changes that cannot be di sti ngui shed from those due to AMI. CK-MB and total CK can be i ncreased with l ong-term exerci se and in chroni c di sease.

No si gnificant increase after pacemaker impl antati on or el ectri cal cardi oversi on.

If CK-MB i s >20% or persi sts >48-72 hrs, consi der atypi cal CK-MB.

y y

Other causes of CK and CK-MB changes are noted. In one protocol the cri teri a for AMI are an increasi ng (above reference range) and then decreasing CK total and CK-MB in seri al specimens drawn on admi ssion and at 8- or 12-hr interval s; this is consi dered almost pathognomonic in pati ents in whom AMI i s strongl y suspected; no bl ood need be coll ected after 48 hrs in patients wi th uneventful course.

CK-MB in peri cardi al fl uid may be hel pful for postmortem di agnosi s of AMI.

Increased Serum Cardiac Troponins T and I

y

Use

Increased cTn implies some myocardi al necrosi s (e.g., anoxi a, contusi on, infl ammati on) even wi thout ECG changes.

Repl ace LD testi ng for l ate di agnosi s of AMI. May repl ace CK-MB as gol d standard.

Ri sk stratifi cati on in pati ents wi th chest pain. Sensiti ve marker for minor myocardi al i njury i n unstabl e angina without AMI. Patients with chest pain, normal CK-MB, nondi agnosti c ECG, and detectabl e cTn have greater ri sk of l ater coronary events.

Di agnosi s of peri operative AMI when CK-MB may be increased by skel etal muscle injury.

Seri al measurements to assess reperfusi on after thrombolytic therapy. Peak cTn after reperfusi on i s rel ated to infarct si ze.

Seri al values may be indi cator of cardi ac allograft rejecti on.

Interpretati on
o

. cTn is about as sensitive as CK-MB during fi rst 48 hrs after AMI; sensitivi ty = 33% from 0 to 2 hrs, 50% from 2 to 4 hrs, 75% from 4 to 8 hrs, and approaches 100% from 8 hrs after onset of chest pain. >85% concordance wi th CK-MB. Specifi city approaches 100%. Hi gh sensitivi ty for 6 days; may remai n i ncreased for ~7-10 days.

. Wi th rapi d ELISA for cTnT, AMI was present in

  

1% of cases with cTnT <0.1 g/L 28% of cases wi th cTnT 0.1-0.19 g/L 88% of cases wi th cTnT 0.2-0.29 g/L

100% of cases with cTnT >4.0 g/L3

P.124

. cTnT may be increased in some pati ents with skeletal muscl e injury, myotonic dystrophy, and chroni c renal failure. cTnI i s not i ncreased by skel etal muscl e injury, whi ch makes it more highly specific for myocardi al injury; may be detected i n some pati ents with renal failure.

. Normal val ues excl ude myocardial necrosi s i n patients with i ncreased CK of skeletal muscle ori gi n (e.g., after arduous physical exerci se).

. Not increased by uncomplicated coronary angi opl asty or electri cal cardi oversi on.

o o

. Not increased by pulmonary or orthopedi c surgery. . Long durati on of increase provi des a l onger di agnosti c window than wi th CK-MB but may make i t di ffi cul t to recogni ze rei nfarcti on.

. cTnI increases ~4-6 hrs after AMI and remai ns increased for 7 days. Rapi d (20 mi ns) test ki t using whol e bl ood is now availabl e.

Comparative Sensitivity 4

Ti me after symptom onset in AMI

Rapi d cTnI

CK-MB mass

CK-MB acti vity

3.52.7 hrs

60%

48%

36%

4 hrs l ater

98%

91%

61%

Unstable angi na

38%

4%

2%

Serum Myoglobin
y

Use
o

Earliest marker for AMI

y y

Interpretati on Increased within 1-3 hrs in >85% of AMI patients, peaks in ~8-12 hrs (may peak within 1 hr) to ~10 upper reference limit, and becomes normal in ~24-36 hrs or l ess; reperfusi on causes peak 4-6 hrs earlier.
o o o

May precede rel ease of CK-MB by 2-5 hrs. Sensi tivity >95% within 6 hrs of onset of symptoms. Myogl obinuri a often occurs.

Di sadvantages

Two or three bl ood samples shoul d be drawn at ~1-hr interval s (myogl obin may be released i n mul tipl e short bursts).

o o

Wi de normal range (6-90 ng/mL). Low speci fici ty for AMI (may al so be i ncreased in renal failure, shock, open heart surgery, and skeletal muscl e damage or exhaustive exerci se, or in patients and carri ers of progressive muscul ar dystrophy, but not by cardi oversi on, cardi ac catheteri zation, or congestive heart failure). Values are usually much hi gher in pati ents with uremi a and muscle trauma than in those with AMI.

CK Isoforms
y

CK-MB and CK-MM are sequenti ally converted in the serum by a carboxypepti dase (CK-MM MB MB-2 MB-1). MM-3 MM-2 MM-1; CK-

y y

Interpretati on . CK-MM and CK-MB isoforms parallel CK-MB but ri se and peak earlier. MB-2/MB-1 and MM-3/MM-1 isoform rati os appear to be the most useful, but methodol ogy for rapi d turnaround time is not wi del y availabl e. Because serum MM-3 i s normally so l ow, its release from damaged cardi ac muscle i s readily evi dent.

Di agnostic MM isoform changes are i ndependent of amount of ti ssue damage, whereas total CK acti vity depends on infarct si ze.

MM-3/MM-1 i soform rati o shows a large change because MM1 i s continually cl eared from the blood. Rati o i s ~1.3 i n control s but >14 in AMI pati ents (1.0 i s a useful cutoff val ue).

MB-2 >1.0 U/L and MB-2/MB-1 ratio >1.5 (normal rati o = 1) i s specifi c for AMI within 4-8 hrs of infarct. Ratio i s >1.5 within 2-4 hrs in >50% of cases, within 4-6 hrs in 92%, and by 8 hrs in 100%. MB-2/MB-1 rati o 1.0 by 4-6 hrs or normal CK-MB by 10 hrs rul es out AMI i n 95% of cases.

MM-3 and MM-3/MM-1 rati o al so increase 2 hrs after intense bri ef exerci se and i n marathon runners. P.125

CK-MB subforms may also be i ncreased i n severe skeletal muscl e damage (e.g., rhabdomyol ysi s) and muscul ar dystrophy.

Isoform rati os return to normal by 24 hrs i n most patients.

Glycogen Phosphorylase BB
y

Use
o

More sensi tive early marker for AMI and unstable angi na within 4 hrs after onset of pai n than i s CK-MB, cTnT, or myogl obi n

Sensi tive marker of peri operati ve myocardi al injury in coronary artery bypass surgery

Interpretati on
o o y

Returns to normal wi thi n 24-36 hrs. Not wi dely avail able. Addi ti onal studi es are needed.

Al so bei ng i nvestigated are serum cardi ac myosin heavy and light chains, fatty acid-bindi ng protei n, al pha-actin, cal citonin gene-related pepti de.

Serum Lactate Dehydrogenase (LD)

y

Use
o o

Repl aced by cTn. Prol onged el evati on l asti ng 10-14 days was formerl y used for late di agnosi s.

Interpretati on
o

Increases in 10-12 hrs, peaks i n 48-72 hrs (~3 normal ).

Increased CK-MB and LD-1/LD-2 rati o >1 ("fli pped" LD) both within 48 hrs (not necessarily at the same time) i s vi rtually di agnostic of AMI.

Increased total LD wi th fli pped LD may also occur in acute renal i nfarcti on, hemol ysis (e.g., hemolyti c anemi a, perni ci ous anemia, prostheti c heart valves), some muscl e di sorders (e.g., polymyosi tis, muscul ar dystrophi es, rhabdomyol ysis), pregnancy, some neopl asms (e.g., small cell of l ung, prostate, testi cul ar germ cell); LD >2000 U suggests a poorer prognosi s.

Serum Aspartate Aminotransferase (AST)

Use
o

Repl aced by other enzymes in diagnosi s of AMI.

Interpretati on
o

AST i s increased i n >95% of the pati ents when bl ood i s drawn at the appropri ate ti me.

Increase appears wi thi n 6-8 hrs, peaks in 24 hrs; level usually returns to normal in 4-6 days.

Peak level is usually ~200 U (5 normal). Val ue >300 U and a more prol onged increase suggest a poorer prognosi s.

Rei nfarcti on i s indi cated by a ri se that foll ows a return to normal .

Serum ALT i s usually not increased unless there i s liver damage due to congestive heart failure, drug therapy, etc.

Serum ALP (from vascul ar endothelium) is increased duri ng reparative phase (4-10 days after onset). Serum GGT i s al so increased.

Leukocytosi s is almost invari abl e; commonl y detected by second day but may occur as early as 2 hrs. WBC i s usually 12,000-15,000; 20,000 is not rare; sometimes it is very hi gh. Usually 75-90% PMNs with onl y a slight shift to the left. Leukocytosi s i s likely to develop before fever.

ESR i s increased, usually by second or thi rd day (may begin within a few hrs); peak rate is in 4-5 days, persi sts for 2-6 mos. ESR is sometimes more sensiti ve than WBC, as increase may occur before fever and persi sts after temperature and WBC have returned to normal . Degree of ESR increase does not correl ate with severity or prognosi s.

CRP i s usually normal in unstable angi na pati ents who have a normal cTnT (<0.1 g/L). Peak CRP correl ates with peak CKMB.

Bl ood l actate i s increased; sensi tivity = 55%, specifici ty = 96% in pati ents presenting wi th acute chest pain.

y y y y

Gl ycosuri a and hyperglycemi a occur in 50% of pati ents. Gl ucose tol erance i s decreased. Laboratory fi ndings due to underl ying coronary heart di sease. Laboratory fi ndings due to sequel ae (e.g., congestive heart failure).

P.126

Myocarditis, Viral
(Routine autopsy inci dence of 1.2-3.5%)

Due To
y

Coxsacki evi rus B (causes most cases i n Uni ted States) and coxsacki evi rus A, echovi rus, poli omyeliti s, influenza A and B, cytomegal ovi rus (CMV), EBV, adenovi rus, rubeol a, mumps, rubell a, vari ol a, vacci nia, varicell a-zoster vi rus (VZV), rabi es, l ymphocyti c chori omeningiti s, chikungunya, dengue, yell ow fever

Serol ogi c tests for vi ral anti gen, IgM anti body, or changed ti ter using acute and conval escent pai red sera

Endomyocardi al bi opsy of ri ght ventri cular muscl e showing >5 lymphocytes/HPF and degenerati on of muscl e fi bers has become major di agnosti c tool to establi sh di agnosi s of myocardi ti s and rul es out other lesi ons (e.g., sarcoi dosi s).

Increased serum markers of myocardi al damage i s common only in earl y stages

o o

cTn sensi tivity = 53%, speci fici ty = 93% CK-MB and CK total <10% sensiti vity

Increased acute phase reactants (e.g., ESR, CRP, mild to moderate leukocytosi s)

Myxoma of Left Atrium

y

Anemia that i s hemol ytic in type and mechanical in ori gin (due to l ocal turbulence of bl ood) shoul d be sought and may be severe. Bi zarre poi kilocytes may be seen in bl ood smear. Reti cul ocyte count may be increased. Other findi ngs may refl ect effects of hemol ysis or compensatory erythroi d hyperpl asi a. The anemi a i s recognized i n ~50% of pati ents with this tumor. Increased serum LD reflects hemol ysis.

Serum gamma gl obulin i s increased i n ~50% of pati ents. IgG may be increased.

y y

Increased ESR i s a refl ecti on of abnormal serum proteins. Pl atel et count may be decreased (possi bly the cause here al so i s mechani cal) with resultant findi ngs due to thrombocytopenia.

Negative bl ood cultures di fferenti ate thi s tumor from bacteri al endocardi ti s.

y y

Occasi onally WBC i s increased, and CRP may be posi tive. Laboratory fi ndings due to complicati ons

Emboli to vari ous organs (i ncreased AST may refl ect many small emboli to stri ated muscle)

o y

Congestive heart failure

These findi ngs are reported much less frequently i n myxoma of the ri ght atri um, which i s more likely to be accompani ed by secondary pol ycythemi a than by anemi a.

Pericardial Effusion, Chronic

y y

See Table 6-2 on body flui ds. Laboratory fi ndings due to underl ying di sease (e.g., TB, myxedema, metastatic tumor, uremi a, SLE). Rarel y due to severe anemi a, scleroderma, pol yarteriti s nodosa, Wegener's granul omatosi s, RA, i rradi ati on therapy, mycotic or vi ral infecti ons, primary tumor of heart, Afri can endomyocardi al fi brosi s, i di opathi c causes.

Pericarditis, Acute Laboratory Findings Due to Primary Disease

y y y

Acti ve rheumatic fever (40% of pati ents) Bacteri al infecti on (20% of patients) Other infecti ons (e.g., vi ral [especi ally coxsacki evi rus B], ri ckettsial , parasiti c, mycobacterial, fungal )
o

Vi ruses are most common i nfecti ous causes.

y y

Uremi a (11% of patients) Beni gn nonspecifi c peri cardi tis (10% of pati ents)

y y

Neopl asms (3.5% of patients) Collagen di sease (e.g., SLE, polyarteri ti s nodosa) (2% of pati ents)

Acute myocardi al i nfarcti on, postcardi ac injury syndrome P.127

y y y

Trauma Myxedema Others (e.g., hypersensi tivity, unknown ori gi n or in associ ati on with vari ous syndromes)

WBC i s usually increased i n proporti on to fever; normal or l ow i n vi ral di sease and tubercul ous peri cardi ti s; markedly increased in suppurative bacteri al peri cardi tis

Examinati on of aspi rated peri cardial flui d (see Table 6-1)

Phlebothrombosis
y

Tests indi cate recent extensi ve cl otti ng of any origin (e.g., postoperative status).
o o

D-dimer test (see Pulmonary Embolism and Infarcti on). Staphyl ococcal cl umpi ng test measures breakdown products of fi bri n i n serum; these indi cate the presence of a cl ot that has begun to di ssolve. Sensitivi ty = 88%, specifi city = 66% using venography as gol d standard.

Seri al diluti on protamine sulfate test measures the presence of a fi brin monomer that i s one of the pol ymeri zati on products of fi bri nogen. It i s l ess

sensi tive than the staphyl ococcal clumping test but indi cates cl otti ng earlier.
y

Laboratory fi ndings of pulmonary infarcti on should be sought as evi dence of emboli zati on.

Polyarteritis Nodosa
y

Tissue bi opsy is basi s for di agnosi s

o o

Fi ndings on bi opsy of small or medium-sized artery. Fi ndings in random skin and muscle bi opsy are confi rmatory i n 25% of patients; most useful when taken from area of tenderness; if no symptoms are present, pectoralis major i s the most useful site.

Testi cul ar bi opsy i s useful when l ocal symptoms are present.

o o

Lymph node and liver bi opsi es are usually not hel pful . Renal bi opsy is not specifi c; often shows gl omerular di sease.

Increased BUN or creati nine; uremi a occurs in 15% of pati ents.

Hepatiti s B surface anti gen (HBsAg) i s present in 20-40% of adul t pati ents.

p-ANCA i s posi tive in 70% of patients; rarel y reflects disease acti vity.

Increased WBC (40,000/cu mm) and PMNs. A ri se i n eosinophil s takes place in 25% of pati ents and i s sometimes very marked; it usually occurs i n pati ents with pulmonary manifestati ons.

ESR and CRP are increased.

Mil d anemi a i s frequent; it may be hemol ytic anemia with posi tive Coombs' test.

Urine i s frequently abnormal .

o o o

Al buminuri a (60% of patients) Hematuri a (40% of pati ents) "Tel escoping" of sedi ment (vari ety of cellular and noncellul ar casts)

y y

Serum gl obulins are increased. Abnormal serum proteins occasi onally occur. Bi ol ogi cal fal seposi tive test for syphilis, ci rcul ati ng anti coagulants, cryogl obulins, macrogl obulins, etc., occurs.

Laboratory fi ndings due to organ invol vement by arteri ti s may be present (e.g., GU, pulmonary, GI, neurol ogi c in >75% of patients).

Prosthetic Heart Valves

y

Complicati ons
o

Hemolysi s-increased serum LD, decreased haptogl obin, reti cul ocytosi s are usual . Severe hemol yti c anemia is uncommon and suggests leakage due to parti al dehi scence of valve or infecti on.

Prostheti c valve infecti on



Early (<60 days after valve repl acement)-usually due to Staphyl ococcus epi dermi di s, S. aureus, gram-negative bacteri a, di phtheroids, fungi; occasi onally due to Mycobacteri a and Legi onell a. 30-80% mortali ty.

Late (>60 days postoperati vel y)-usually due to streptococci . S. epi dermi di s i s common up to 12 mos after surgery. 20-40% mortality.

. Bl ood cul ture posi tive in >90% of pati ents unl ess received anti bi otic therapy, i nfecti on involves fasti di ous organi sm (e.g., HACEK [Haemophilus-Actinobacillus-Cardi obacteri umEi kenella-Ki ngella]), P.128

or i dentifi cati on requi res speci al techni que (e.g., Ri ckettsi a, fungi , mycobacteri a, Legi onella).
y

Surgery i s i ndicated if bl ood culture i s positive after 5 days of appropri ate anti microbi al therapy or infecti on is recurrent. Infection wi th organi sms other than Streptococcus usually requi re val ve repl acement.
o

Complicati ons of anticoagul ant therapy

Rheumatic Fever, Acute5

y

Increased serum cTn implies some myocardi al necrosi s due to myocardi tis.

Laboratory confi rmati on of preceding group A streptococcal infecti on

o o

Increased titer of anti streptococcal anti bodies Posi tive throat culture for group A Streptococcus and recent scarlet fever

Serol ogi c tests-see bel ow

Serol ogi c ti ters: one of the foll owing is elevated in 95% of pati ents with acute rheumati c fever; i f all are normal , a di agnosi s of rheumatic fever i s less likely.
o

ASOT increase i ndicates recent group A Streptococcus pharyngi tis within the l ast 2 mos. Increased titer devel ops only after the second week and reaches a peak in 4-6 wks. Increasing titer is more si gnifi cant than a singl e determi nati on. Ti ter i s usually >250 U; more si gni ficant if >400-500 U. A normal titer hel ps to rule out clini cally doubtful rheumatic fever. Sometimes ASOT i s not i ncreased even when other titers are i ncreased. Hei ght of titer is not rel ated to severity; rate of fall i s not rel ated to course of di sease.

Anti -DNase B assay shoul d al so be performed because >15% of patients with acute rheumati c fever do not have an i ncreased ASOT. This assay i s superi or to ASOT in detecting anti bodies after group A streptococcal skin infecti ons and is less prone to fal se-posi tive reacti ons; l onger peri od of reactivi ty is hel pful in pati ents wi th i sol ated chorea or cardi ti s, who may have a l ong l atent peri od before manifesting rheumati c fever duri ng whi ch ASOT may have returned to normal .

Anti hyaluroni dase ti ter of 1000-1500 U foll ows recent group A streptococcal di sease and 4000 U wi th rheumati c fever. Average titer is hi gher in earl y rheumati c fever than i n subsi ding or inactive rheumati c fever or nonrheumati c streptococcal di sease or nonstreptococcal infecti ons. Antihyaluroni dase titer i s increased as often as ASOT and anti fi brinol ysin ti ter.

Anti fibri nolysi n (anti streptokinase) ti ter i s i ncreased in rheumati c fever and i n recent hemol yti c streptococcus infecti ons.

Acute phase reactants (ESR, CRP, i ncreased WBC) are mi nor manifestati ons.
o

ESR increase is a sensitive test of rheumati c acti vity; ESR returns to normal after adequate treatment wi th ACTH or salicylates. It may remain i ncreased after WBC becomes normal . It i s sai d to become normal with onset of congestive heart failure even in the presence of rheumati c acti vity. It i s normal i n uncompli cated chorea al one.

o o

CRP parall els ESR. WBC may be normal but usually i s increased (10,00016,000/cu mm) with shift to the l eft; i ncrease may persi st for weeks after fever subsides. Count may decrease with sali cyl ate and ACTH therapy.

Serum proteins are al tered, with decreased serum albumin and increased al pha 2 and gamma gl obulins. (Streptococcus group A i nfecti ons do not increase al pha 2 gl obulin.) Fi bri nogen i s increased.

Anemi a (Hb usually 8-12 gm/dL) i s common; gradually improves as activity subsi des; microcyti c type. Anemia may be rel ated to increased pl asma volume that occurs in earl y phase of acute rheumati c fever.

Urine: A slight febril e al buminuri a i s present. Often mild abnormality of protei n, casts, RBCs, WBCs i ndi cates mil d focal nephri tis. Concomitant GN appears i n 2.5% of cases. P.129

Bl ood cultures are usually negati ve. Occasi onal positi ve cul ture i s found in 5% of patients (bacteri a usually grow only in fl uid medi a, not on soli d medi a), i n contrast to bacteri al endocarditi s.

y y

Throat culture i s often negative for group A streptococci . Serum AST may be i ncreased, but ALT i s normal unless the pati ent has cardi ac failure with liver damage.

Determi ne clini cal acti vity-foll ow ESR, CRP, and WBC. Return to normal shoul d be seen i n 6-12 wks in 80-90% of patients; it may take 6 mos. Normal findi ngs do not prove inactivi ty if pati ent is receiving hormone therapy. When therapy i s stopped after findings have been suppressed for 6-8 wks, a mil d rebound may be seen for 2-3 days foll owed by a return to normal . Rel apse after cessati on of therapy occurs wi thi n 1-8 wks.

Shock
y

Leukocytosi s is common, especially with hemorrhage. Leukopeni a may be present when shock i s severe, as in gram-negative bacteremi a. Ci rcul ati ng eosi nophils are decreased.

Hemoconcentrati on (e.g., dehydrati on, burns) or hemodiluti on (e.g., hemorrhage, crush injuries, and skeletal trauma) takes place.

Aci dosi s appears when shock i s well devel oped, wi th increased bl ood lactate, l ow serum sodium, l ow CO 2 combini ng power with decreased alkaline reserve.

Bl ood pH i s usually rel ati vel y normal but may be decreased. BUN and creatinine may be i ncreased.

y y y

Serum potassium may be i ncreased. Hypergl ycemi a occurs earl y. Urine examinati on
o

Vol ume: Normovolemi c patients have output 50 mL/hr; cause shoul d be investi gated if <25-30 mL/hr. In hypovol emi a, normal ki dney may lower 24-hr urine output to 300-400 mL.

Specifi c gravi ty: >1.020 with l ow urine output suggests pati ent i s flui d depl eted. <1.010 with l ow uri ne output suggests renal insuffi ci ency. Speci fi c gravity depends on wei ght rather than concentrati on of sol utes; therefore it i s more affected than osmol arity by high-mol ecularwei ght substances such as urea, albumi n, and gl ucose.

Osmol arity: Hypovol emia is suggested by hi gh uri ne osmol arity and uri ne-pl asma osmolari ty rati o of 1:2. Renal failure i s suggested by l ow uri ne osmol arity wi th oli guri a and urine/plasma osmol arity rati o of 1:1.

Systemic Capillary Leak Syndrome6

y

(Very rare recurring i di opathi c di sorder in adul ts wi th sudden transi ent extravasati on of <70% of pl asma; very hi gh morbi dity and mortali ty; hypotension i s part of tri ad)

Hemoconcentrati on (e.g., l eukocytosi s; Hb may be ~25 gm/dL)

y y

Hypoal bumi nemi a Monocl onal gammopathy (especi ally IgG wi th kappa or l ambda light chain) without evi dence of multi ple myel oma is often present. Some pati ents may progress to multi pl e myel oma.

Laboratory fi ndings due to complicati ons (e.g., rhabdomyol ysi s, acute tubular necrosi s, pleural /pericardi al effusi on)

Takayasu's Syndrome (Arteritis)

y

Increased ESR in ~75% of cases during acti ve di sease but normal in only one-half during remi ssi on

y y

WBC usually normal Serum proteins abnormal with increased gamma gl obulins (mostly composed of IgM)

Female patients have a conti nuous hi gh level of urinary total estrogens (rather than the usual rise duri ng luteal phase after a l ow excreti on duri ng follicular phase).

Laboratory tests not useful for di agnosi s or to guide management.

Di agnosi s i s established by characteri sti c arteri ographi c changes or hi stol ogi c examinati on.

P.130

Thromboangiitis Obliterans (Buerger's Disease)

y

(Vascul ar inflammati on and occl usion of intermedi ate-si zed arteries and vei ns of extremiti es)

Laboratory tests are usually normal .

Thrombophlebitis, Septic
y

Laboratory fi ndings due to associ ated septi cemi a

o

Increased WBC (often >20,000/cu mm) wi th marked shi ft to l eft and toxi c changes in neutrophil s.

o o

DIC may be present. Respi ratory alkal osi s due to ventilati on-perfusi on abnormalities with hypoxi a. Significant aci dosi s indi cates shock.

o o

Azotemi a. Posi tive bl ood culture (S. aureus is most frequent organi sm; others are Klebsi ella, Pseudomonas aerugi nosa, enterococci , Candi da).

Laboratory fi ndings due to complicati ons (e.g., septic pul monary infarcti on)

Laboratory fi ndings due to underl ying di sease

Transplant Rejection (Acute) of Heart

y

Endocardi al bi opsy to determine acute rejecti on and foll ow effects of therapy has no substi tute.

Increasi ng ESR and WBC

Increased i soenzyme LD-1 as amount (>100 IU) and percentage (35%) of total LD duri ng fi rst 4 wks after surgery

These findi ngs are reversed with effecti ve immunosuppressive therapy. Total LD conti nues to be increased even when LD-1 becomes normal .

Chroni c rejecti on is accel erated coronary artery atheroscl erosi s.

Valvular Heart Disease

y

Laboratory fi ndings due to associ ated or underlying or predi sposi ng di sease (e.g., syphilis, rheumati c fever, carci noi d syndrome, geneti c di sease of mucopol ysacchari de metaboli sm, congeni tal defects)

Laboratory fi ndings due to complicati ons (e.g., heart failure, bacteri al endocardi ti s, emboli c phenomena)

Vasculitis, Classification By Etiology

y

Pri mary
o o o o

Pol yarteri ti s nodosa Wegener's granul omatosi s Gi ant cell arteri ti s Hypersensitivity vasculitis

Secondary
o

Infections


Bacteri a (e.g., septi cemi a due to Gonococcus or Staphyl ococcus)

    o

Mycobacteri a Vi ruses (e.g., CMV, HBV) Ri ckettsi a (e.g., Rocky Mountain spotted fever) Spi rochetes (e.g., syphili s, Lyme di sease)

Associ ated with malignancy (e.g., mul tipl e myel oma, lymphomas)

Connective ti ssue di seases

  

RA SLE Sjgren's syndrome

Di seases that may simul ate vasculiti s (e.g., ergotamine toxi ci ty, chol esterol emboli zati on, atri al myxoma)

P.131

By Size of Involved Vessel (Noninfectious Vasculitis)

y

Large vessel
o o

Takayasu's arteri tis Gi ant cell (temporal) arteriti s

Medium-si zed vessel

o o o

Pol yarteri ti s nodosa Kawasaki 's disease Pri mary granul omatous CNS vasculiti s

Small vessel
o

ANCA-associ ated vasculiti s

    o

Wegener's granul omatosi s Churg-Strauss syndrome Drug induced Mi croscopi c pol yangiiti s

Immune complex-type vasculiti s

        

Henoch-Schnlei n purpura Cryogl obulinemi a Rheumatoi d vasculitis SLE Sjgren's syndrome Goodpasture's syndrome Behet's di sease Drug induced Serum si ckness

Paraneopl asti c vasculitis (lymphoproliferative, myel oproliferative, carcinoma)

Infl ammatory bowel di sease

Wegener's Granulomatosis7
y

(Necroti zing granul omatous vasculiti s affecti ng respi ratory tract; di sseminated form shows renal involvement)

Di agnosi s i s established by bi opsy of affected ti ssue wi th cul tures and speci al stains that exclude mycobacteri al and fungal infecti on.

Antineutrophil Cytoplasmic Antibodies (ANCA)

y y

Use Ai d i n di agnosi s and cl assifi cati on of vari ous vasculiti sassoci ated and autoi mmune di sorders.

y y

Interpretati on c-ANCA (anti-proteinase 3; coarse di ffuse cytopl asmi c pattern) i s hi ghl y specifi c (>90%) for acti ve Wegener's granul omatosi s. Sensitivi ty >90% in systemic vasculiti c phase ~65% in predomi nantly granul omatous di sease of respi ratory tract, ~30% duri ng compl ete remissi on. Hei ght of ELISA titer does not correl ate with di sease activi ty; hi gh ti ter may persi st duri ng remi ssi on for years. Al so occasionally found in other vasculitides (pol yarteriti s nodosa, mi croscopi c pol yangiiti s [e.g., lung, idi opathic crescenti c and pauciimmune GN], Churg-Strauss vasculiti s).

p-ANCA (agai nst vari ous proteins [e.g., myel operoxi dase, el astase, l ysozyme], peri nucl ear pattern) occurs only wi th fi xati on i n al cohol , not formalin. Posi tive result shoul d be confi rmed by ELISA. Has poor specifi city and 20-60% sensi tivity i n a vari ety of autoi mmune di seases (microscopi c pol yangiiti s, Churg-Strauss vasculiti s, SLE, infl ammatory bowel di sease, Goodpasture's syndrome, Sjgren's syndrome, i di opathi c GN, chroni c infecti on). However, pulmonary small vessel vasculiti s is strongl y linked with myel operoxi dase anti bodi es.

Both p-ANCA and c-ANCA may be found in non-immune medi ated pol yarteri ti s and other vasculi tides.

Atypi cal pattern (neither c-ANCA or p-ANCA; unknown target anti gens) has poor specifi city and unknown sensiti vity in vari ous conditi ons (e.g., HIV infecti on, endocardi tis, cysti c

fi brosi s, Felty's syndrome, Kawasaki syndrome, ul cerative coliti s, Crohn's di sease). P.132

Laboratory fi ndings refl ecting specifi c organ invol vement

o

Ki dneys-renal di sease in ~80% of cases. Hematuri a (>5 RBCs/HPF), proteinuri a, azotemi a. Nephrosi s or chroni c nephri tis may occur. Most patients devel op renal insuffi ciency. Bi opsy most frequently shows focal necroti zi ng GN with crescent formati on; coarse granular pattern wi th immunofluorescent staini ng. Bi opsy is important to defi ne extent of disease.

o o o y

CNS. Respi ratory tract. Heart.

Nonspecifi c laboratory findings

o

Normochromi c anemia, thrombocytosi s, and mil d leukocytosi s occur i n 30-40% of pati ents; eosi nophilia may occur but i s not a feature. Leukopeni a or thrombocytopenia occur only duri ng cytotoxic therapy.

ESR i s increased in 90% of cases, often to very hi gh levels; CRP level correl ates with disease activity even better than ESR.

Serum gl obulins (IgG and IgA) are i ncreased in up to 50% of cases.

o o

Serum C3 and C4 compl ement level s may be increased. RF may be present in l ow ti ter i n two-thi rds of cases.

o y

ANA i s negati ve.

Laboratory fi ndings due to secondary i nfecti on (usually staphyl ococcal) of si nus, mucosal , pul monary l esi ons.

Laboratory fi ndings due to therapy (e.g., bl adder cancer and sterility due to cycl ophosphamide therapy).

REFERENCES
1. Included in Ameri can College of Rheumatol ogy 1990 criteri a for cl assifi cati on of vasculitis. Arthriti s Rheum 1990;33:1068. 2. Stewart JT, et al . Earl y noninvasive i dentifi cati on of failed reperfusi on after intravenous thrombolyti c therapy in acute myocardi al infarcti on. J Am Coll Cardi ol 1998;31:1499. 3. Gerhardt W, et al . An improved rapi d troponin T test wi th a decreased detecti on limi t: a mul ticentre study of the anal yti cal and clini cal performance in suspected myocardial damage. Scand J Clin Lab Invest 1997;57:549. 4. Heeschen C, et al . Anal yti cal performance and clini cal appli cati on of new rapi d bedsi de assay for the detecti on of serum cardi ac troponi n I. Clin Chem 1998;44:1925. 5. Speci al Writi ng Group, Commi ttee on Rheumati c Fever, Endocarditi s, and Kawasaki Di sease, Council on Cardi ovascul ar Di sease in the Young, Ameri can Heart Associ ati on. Gui delines for the diagnosi s of rheumati c fever: Jones Cri teri a, 1992 update. JAMA 1992;268:2069.

6. Tahi rkheli NK, Grei pp PR. Treatment of the systemic capillary leak syndrome with terbutaline and theophylline. Ann Intern Med 1999;130:905. 7. Included in Ameri can College of Rheumatol ogy 1990 criteri a for cl assifi cati on of vasculitis. Arthriti s Rheum 1990;33:1068