Laboratory Laboratory InterpretationInterpretation

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KIDNEYKIDNEY

CreatinineCreatinine Creatine is synthesized in the liver. Creatine is synthesized in the liver.

It is the chief source of high-energy It is the chief source of high-energy phosphocreatine for muscle phosphocreatine for muscle metabolism. metabolism.

It loses water to become creatinine, It loses water to become creatinine, all of which is excreted.all of which is excreted.

Use for renal functionUse for renal function

casecase Male 60 years old came with fatigue Male 60 years old came with fatigue

BUN=40/Cr=2BUN=40/Cr=2 This is renal failure –renal /prerenal?This is renal failure –renal /prerenal?

Old man will lose muscle mass that Old man will lose muscle mass that makes low Cr.makes low Cr.

It might be prerenal or renal failure. It might be prerenal or renal failure. You will ask for U/A to look for You will ask for U/A to look for sp.Gr.sp.Gr.

Urine hCG Urine hCG Normal pregnancy -secreted first by Normal pregnancy -secreted first by

trophoblastic cells of conceptus and trophoblastic cells of conceptus and later by placentalater by placenta

positive as early as 4 days after positive as early as 4 days after expected date of menstruationexpected date of menstruation

it is >95% reliable by the 10th to the it is >95% reliable by the 10th to the 14th day. Human chorionic 14th day. Human chorionic gonadotropin (hCG) increases to a gonadotropin (hCG) increases to a peak between the 60th and 70th days peak between the 60th and 70th days then decreases progressively. then decreases progressively.

Urine hCGUrine hCG False-Positive ResultFalse-Positive Result -Drugs, e.g., chlorpromazine, -Drugs, e.g., chlorpromazine,

phenothiazinesphenothiazines-Bacterial contamination-Bacterial contamination-Protein or blood in urine -Protein or blood in urine False-Negative Result False-Negative Result -Dilute urine-Dilute urine-Missed abortion-Missed abortion-Dead fetus syndrome-Dead fetus syndrome

Hematuria Hematuria <3% of normal persons ( ≥3 <3% of normal persons ( ≥3

RBCs/HPF )RBCs/HPF ) 18% of persons after very 18% of persons after very

strenuous exercise. strenuous exercise. The source of microscopic The source of microscopic

hematuria remains obscure in hematuria remains obscure in ~70% of cases after workup~70% of cases after workup..

Nonglomerular Nonglomerular HematuriaHematuria

Caused ByCaused By TraumaTrauma Hemoglobinopathies Hemoglobinopathies Polycystic diseasePolycystic disease GU tract tumors, infectionsGU tract tumors, infections

Hematuria in ChildrenHematuria in ChildrenCaused ByCaused By-Glomerular Causes-Glomerular Causes Acute postinfectious GNAcute postinfectious GN Membranoproliferative GNMembranoproliferative GN IgG-IgA nephropathy (Berger disease)IgG-IgA nephropathy (Berger disease) Hereditary nephritis (Alport syndrome)Hereditary nephritis (Alport syndrome) SLESLE Renal infarctionRenal infarction Henoch-Schönlein purpuraHenoch-Schönlein purpura-Nonglomerular Causes-Nonglomerular Causes Polycystic kidneysPolycystic kidneys Renal tumorsRenal tumors HydronephrosisHydronephrosis GU tract infection, foreign body, calculi, etc. GU tract infection, foreign body, calculi, etc.

KetonuriaKetonuria is diagnosed when ketone bodies is diagnosed when ketone bodies

(acetone, beta-hydroxybutyric acid, (acetone, beta-hydroxybutyric acid, acetoacetic acid) appear in urine.acetoacetic acid) appear in urine.

Use Screening for ketoacidosis, Use Screening for ketoacidosis, especially in diabetes mellitus when especially in diabetes mellitus when blood is not immediately availableblood is not immediately available

casecase 30 year-old Female came with 30 year-old Female came with

kussmual breathing and underlying kussmual breathing and underlying DMDM

Her BS= 500, Hco3=10,urine Her BS= 500, Hco3=10,urine ketone-negketone-neg

What is her diagnosis?What is her diagnosis?

DKADKA Measure serum ketone or urine Measure serum ketone or urine

ketone cannot measure beta-ketone cannot measure beta-hydroxybutyric acid ( measure hydroxybutyric acid ( measure esp.acetoacetate /acetone)esp.acetoacetate /acetone)

DKA +lactic acidosis have high beta-DKA +lactic acidosis have high beta-hydroxybutyric acid hydroxybutyric acid

KetonuriaKetonuria Metabolic conditions (e.g., diabetes Metabolic conditions (e.g., diabetes

mellitus, renal glycosuria)mellitus, renal glycosuria) Dietary conditions (e.g., starvation, Dietary conditions (e.g., starvation,

high-fat diets)high-fat diets) Increased metabolic requirements Increased metabolic requirements

(e.g., hyperthyroidism, fever, (e.g., hyperthyroidism, fever, pregnancy and lactation)pregnancy and lactation)

Prerenal azotemiaPrerenal azotemia specific gravity >1.030 and specific gravity >1.030 and Urine osmolality >500 mOsm/kg)Urine osmolality >500 mOsm/kg)

ProteinuriaProteinuria

Transient(10%)Transient(10%) high feverhigh fever CHFCHF HTHT Stress exposure to cold, strenuous Stress exposure to cold, strenuous

exercise, seizures.exercise, seizures.

Usually <2 g/d; disappears with Usually <2 g/d; disappears with recovery from precipitating cause.recovery from precipitating cause.

ProteinuriaProteinuriaPERSISTENTPERSISTENTGlomerular Glomerular Idiopathic (e.g., membranoproliferative GN, Idiopathic (e.g., membranoproliferative GN,

membranous glomerulopathy)membranous glomerulopathy) SecondarySecondary

Infection (e.g., poststreptococcal, hepatitis Infection (e.g., poststreptococcal, hepatitis B, bacterial endocarditis, malaria)B, bacterial endocarditis, malaria)

Vascular (e.g., renal artery stenosis)Vascular (e.g., renal artery stenosis) Drugs (e.g.NSAIDS, heroine, captopril, Drugs (e.g.NSAIDS, heroine, captopril,

penicillamine)penicillamine) Autoimmune (e.g., SLE, RA, Autoimmune (e.g., SLE, RA,

dermatomyositis, Henoch-Schönlein dermatomyositis, Henoch-Schönlein purpura, ulcerative colitis)purpura, ulcerative colitis)

NeoplasiaNeoplasia

MicroalbuminuriaMicroalbuminuria

Microalbuminuria is defined as Microalbuminuria is defined as persistent proteinuria that is below persistent proteinuria that is below detection by routine reagent strips detection by routine reagent strips but greater than normal.but greater than normal.

MicroalbuminuriaMicroalbuminuria

patients with DM: microalbuminuriapatients with DM: microalbuminuria associated with associated with longerlonger duration of duration of

diabetes, diabetes, poorerpoorer glycemic control, glycemic control, higher higher BP, BP, advancedadvanced retinopathy and retinopathy and neuropathy, subsequent neuropathy, subsequent renal renal failurefailure, and , and increasedincreased vascular vascular damage and risk for cardiovascular damage and risk for cardiovascular disease.disease.

Bence-Jones ProteinuriaBence-Jones Proteinuria UseDetection of various gammopathiesUseDetection of various gammopathies 80% of tests are true positive-Myeloma 80% of tests are true positive-Myeloma

(70% ) (70% )

False positiveFalse positive CNT (e.g., RA, SLE, scleroderma)CNT (e.g., RA, SLE, scleroderma) Chronic renal insufficiencyChronic renal insufficiency Lymphoma /leukemiaLymphoma /leukemia Metastatic carcinoma of lung, Metastatic carcinoma of lung,

gastrointestinal, or GU tractsgastrointestinal, or GU tracts

AnuriaAnuria < 100 mL of urine in 24 hours.< 100 mL of urine in 24 hours. Caused ByCaused By Bilateral complete urinary tract Bilateral complete urinary tract

obstructionobstruction Acute cortical necrosisAcute cortical necrosis Necrotizing glomerulonephritisNecrotizing glomerulonephritis Certain causes of acute tubular Certain causes of acute tubular

necrosisnecrosis

OliguriaOliguria is usually defined as excretion of less is usually defined as excretion of less

than 400 mL of urine in 24 hours(in than 400 mL of urine in 24 hours(in children< 15 to 20 mL/kg/24 h)children< 15 to 20 mL/kg/24 h)

Caused ByCaused By Prerenal causes (e.g., CHF, shock)Prerenal causes (e.g., CHF, shock) Postrenal causes Postrenal causes Renal causesRenal causes

PolyuriaPolyuria urine volume > 2,000 mL / day.urine volume > 2,000 mL / day. Caused ByCaused By Osmotic diuresis( DM)Osmotic diuresis( DM) Polydipsia(DI)Polydipsia(DI) Diuretic drugsDiuretic drugs Chronic renal failureChronic renal failure Partial obstruction of urinary tract with Partial obstruction of urinary tract with

impaired urinary concentration functionimpaired urinary concentration function acute tubular necrosis acute tubular necrosis

(aminoglycosides)(aminoglycosides)

CARDIOCARDIO

Acute rheumatic fever Acute rheumatic fever occurring 10 days to 6 weeks occurring 10 days to 6 weeks

following an episode of group A following an episode of group A Streptococcus infection.Streptococcus infection.

Diagnostic criteria confirmation of Diagnostic criteria confirmation of preceding group A Streptococcus preceding group A Streptococcus infection byinfection by

1.Positive throat culture 1.Positive throat culture 2.2.Increased serologic titer of Increased serologic titer of

antistreptococcal antibodies antistreptococcal antibodies

Acute rheumatic feverAcute rheumatic fever Symptom+2 major / 1 major + 2 Symptom+2 major / 1 major + 2

minorminor Minor Criteria: High ESR or CRP, Minor Criteria: High ESR or CRP,

prolonged P-R interval, fever, prolonged P-R interval, fever, arthralgiaarthralgia

Major Criteria: Carditis, arthritis, Major Criteria: Carditis, arthritis, Sydenham chorea, subcutaneous Sydenham chorea, subcutaneous nodules, erythema marginatumnodules, erythema marginatum

To determine clinical activity—To determine clinical activity—follow ESR, CRP, and WBC. follow ESR, CRP, and WBC.

Return to normal should be seen Return to normal should be seen in 6 to 12 weeks in 80% to 90% of in 6 to 12 weeks in 80% to 90% of patientspatients

it may take ≤6 monthsit may take ≤6 months

Cor PulmonaleCor Pulmonale polycythemiapolycythemia Increased blood CO2 Increased blood CO2 the primary lung disease (e.g., the primary lung disease (e.g.,

chronic bronchitis and chronic bronchitis and emphysemaemphysema

Blood lipid tests Blood lipid tests should not be performed during should not be performed during

stress or acute illness (2 to 3 stress or acute illness (2 to 3 months after illness )months after illness )

after a 12- to 13-hour fastafter a 12- to 13-hour fast

Myocardial InfarctionMyocardial Infarction Characteristics of Serum Markers for Characteristics of Serum Markers for

Myocardial DamageMyocardial Damage Early appearanceEarly appearance: Myoglobin, CK isoforms: Myoglobin, CK isoforms High specificityHigh specificity: cTnI, cTnT, CK-MB, CK : cTnI, cTnT, CK-MB, CK

isoformsisoforms

Wide diagnostic windowWide diagnostic window: cTnT, cTnI, LD : cTnT, cTnI, LD

Risk stratificationRisk stratification: cTnT, cTnI, CK-MB: cTnT, cTnI, CK-MB

Predicts reperfusionPredicts reperfusion: Myoglobin, cTnI, cTnT, : Myoglobin, cTnI, cTnT, CK isoformsCK isoforms

Indicates reinfarction after 2–4 dIndicates reinfarction after 2–4 d: CK-MB: CK-MB

cTncTn cTn is as sensitive as CK-MB during cTn is as sensitive as CK-MB during

the first 48 hours after AMI the first 48 hours after AMI Specificity close to 100%. High Specificity close to 100%. High

sensitivity for 6 days. sensitivity for 6 days. cTnT may remain increased for ≤14 cTnT may remain increased for ≤14

days.days.

cTncTn cTnI is not increased by skeletal cTnI is not increased by skeletal

muscle injury, making it more highly muscle injury, making it more highly specific for myocardial injury. specific for myocardial injury.

cTnI/ cTnT may be detected in 10% cTnI/ cTnT may be detected in 10% to 30% of patients with CRFto 30% of patients with CRF

CPK-MBCPK-MBUse inUse in Detect reinfarction or extension Detect reinfarction or extension

of MI after 72 hours.of MI after 72 hours. Document reperfusion after Document reperfusion after

thrombolytic therapy.thrombolytic therapy.

CK-MB usually is evident at 4 to CK-MB usually is evident at 4 to 8 hours, peaks at 15 to 24 hours 8 hours, peaks at 15 to 24 hours

Serum MyoglobinSerum Myoglobin is an oxygen-carrying respiratory is an oxygen-carrying respiratory

protein found only in skeletal and protein found only in skeletal and cardiac muscle.cardiac muscle.

Earliest marker for AMI.Earliest marker for AMI. Increased 1 to 3 hours in >85% of AMI Increased 1 to 3 hours in >85% of AMI

patientspatients peaks 8 to 12 hours peaks 8 to 12 hours becomes normal in about 24 to 36 becomes normal in about 24 to 36

hours or less; hours or less;

B-type Natriuretic B-type Natriuretic Peptide Peptide

hormone secreted by myocytes in the hormone secreted by myocytes in the ventricles in response to pressure ventricles in response to pressure overload/myocyte stretch overload/myocyte stretch

use: BNP / N-terminal (NT) proBNP. use: BNP / N-terminal (NT) proBNP. Use inUse in- screening and diagnosis of CHF - screening and diagnosis of CHF -Prognostic tool for classes III and IV -Prognostic tool for classes III and IV -Diagnosis of left ventricular dysfunction -Diagnosis of left ventricular dysfunction

B-type Natriuretic B-type Natriuretic PeptidePeptide

cutoff values :cutoff values : BNP: 80 to 100 pg/mLBNP: 80 to 100 pg/mL NT-proBNP: 125 pg/mL for age <75NT-proBNP: 125 pg/mL for age <75

Reading <100 pg/mL rules out CHF Reading <100 pg/mL rules out CHF as cause of dyspnea.as cause of dyspnea.

Reading >400 pg/mL indicates 95% Reading >400 pg/mL indicates 95% likelihood of CHF likelihood of CHF

B-type Natriuretic B-type Natriuretic PeptidePeptide

Increase in BNP in right heart Increase in BNP in right heart failure is less than in left ventricular failure is less than in left ventricular dysfunction dysfunction

BNP and NT-proBNP can be BNP and NT-proBNP can be increased in renal failure, especially increased in renal failure, especially if dialysis is needed if dialysis is needed

Secondary hypertensionSecondary hypertension causes <10% of cases of causes <10% of cases of

hypertension.hypertension.

Many causes for secondary HT=?Many causes for secondary HT=?

Secondary hypertensionSecondary hypertension Endocrine diseasesEndocrine diseases

Adrenal, e.g., pheochromocytoma, Cushing Adrenal, e.g., pheochromocytoma, Cushing syndromesyndrome

Pituitary disease, e.g., acromegalyPituitary disease, e.g., acromegaly Hyperthyroidism, hyperparathyroidism, etc.Hyperthyroidism, hyperparathyroidism, etc.

Renal diseasesRenal diseases renal artery stenosis, nephrosclerosis, renal artery stenosis, nephrosclerosis,

embolismembolism Parenchymal, e.g., glomerulonephritis, Parenchymal, e.g., glomerulonephritis,

polycystic kidneyspolycystic kidneys Other, e.g., toxemia of pregnancy, polycythemia, Other, e.g., toxemia of pregnancy, polycythemia,

acute porphyriaacute porphyria Drugs, e.g., oral contraceptives, tricyclic Drugs, e.g., oral contraceptives, tricyclic

antidepressants, licoriceantidepressants, licorice Toxic substances, e.g., poisoning by lead or Toxic substances, e.g., poisoning by lead or

cadmiumcadmium

HT+ Hypo KHT+ Hypo K Ought to think about many Ought to think about many

diseases?diseases?

HT+ Hypo K HT+ Hypo K Primary aldosteronismPrimary aldosteronism Pseudoaldosteronism (caused by Pseudoaldosteronism (caused by

excessive ingestion of licorice)excessive ingestion of licorice) Secondary aldosteronism, e.g., Secondary aldosteronism, e.g.,

malignant hypertensionmalignant hypertension Hypokalemia caused by diuretic Hypokalemia caused by diuretic

administrationadministration Potassium loss caused by renal Potassium loss caused by renal

diseasedisease Cushing syndromeCushing syndrome

Infective endocarditis Infective endocarditis (IE) (IE)

2 major criteria2 major criteria 1 major plus 3 minor criteria1 major plus 3 minor criteria 5 minor criteria 5 minor criteria pathologic findings (vegetation pathologic findings (vegetation

or intracardiac abscess or intracardiac abscess confirmed histologically showing confirmed histologically showing active endocarditis).active endocarditis).

Major CriteriaMajor Criteria Typical organism in ≥2 blood cultures in Typical organism in ≥2 blood cultures in

absence of primary focus, or persistently absence of primary focus, or persistently positive blood cultures drawn >1 hour positive blood cultures drawn >1 hour apartapart

Involvement of endocardium by Involvement of endocardium by echocardiogram or valve regurgitationechocardiogram or valve regurgitation

Positive serology for Coxiella burnetii Positive serology for Coxiella burnetii (IgG >1:800)(IgG >1:800)

Bacterial or fungal DNA in blood or Bacterial or fungal DNA in blood or valve (including Bartonella sp., valve (including Bartonella sp., Tropheryma whipplei, other new or Tropheryma whipplei, other new or unusual organisms)unusual organisms)

S. aureus bacteremia, even if nosocomial S. aureus bacteremia, even if nosocomial or removable source of infection is or removable source of infection is presentpresent

Positive echocardiogram (e.g., Positive echocardiogram (e.g., oscillating intracardiac mass)oscillating intracardiac mass)

Typical pathogen in IETypical pathogen in IE Streptococcus viridans Streptococcus viridans

[~50% of cases][~50% of cases] S. bovisS. bovis Staphylococcus aureusStaphylococcus aureus HACEK [Haemophilus, HACEK [Haemophilus,

Actinobacillus, Actinobacillus, Cardiobacterium, Eikenella, Cardiobacterium, Eikenella, Kingella]Kingella]

Minor CriteriaMinor Criteria Risk factors: predisposing heart condition / Risk factors: predisposing heart condition /

IV drug abuseIV drug abuse Fever >38°C (100.4°F)Fever >38°C (100.4°F) Vascular phenomena: septic pulmonary Vascular phenomena: septic pulmonary

infarcts, major arterial emboli, infarcts, major arterial emboli, Janeway Janeway lesionslesions

Immunologic phenomena: Immunologic phenomena: Osler nodesOsler nodes, Roth , Roth spotsspots

Microbiologic evidence: positive blood culture Microbiologic evidence: positive blood culture other than major criteria or positive serologic other than major criteria or positive serologic findings (Bartonella sp. or Chlamydia sp.)findings (Bartonella sp. or Chlamydia sp.)

Clinical: newly diagnosed clubbing or splinter Clinical: newly diagnosed clubbing or splinter hemorrhages , microscopic hematuria hemorrhages , microscopic hematuria

Biochemical: CRP >100 mg/L or ESR >30 Biochemical: CRP >100 mg/L or ESR >30 mm/hmm/h

Risk FactorsRisk Factors Preexisting valve disease / congenital heart Preexisting valve disease / congenital heart

diseasesdiseases Nosocomial: most are caused by enterococci and Nosocomial: most are caused by enterococci and

staphylococci. Case fatality >50%:staphylococci. Case fatality >50%: IV lines; S. aureus in patients with central venous IV lines; S. aureus in patients with central venous

catheters, parenteral lines for feeding or catheters, parenteral lines for feeding or chemotherapychemotherapy

Hemodialysis patients: >50% are caused by S. Hemodialysis patients: >50% are caused by S. aureusaureus

S. bovis in patients with colon cancer causes 20% of S. bovis in patients with colon cancer causes 20% of casescases

Enterococcus faecalis in patients: genitourinary Enterococcus faecalis in patients: genitourinary procedures, pelvic infections, prostate diseaseprocedures, pelvic infections, prostate disease

Blood culture is positive in 80% to 90% of patients:Blood culture is positive in 80% to 90% of patients:

Proper blood cultures require Proper blood cultures require adequate volume of blood, at least five adequate volume of blood, at least five cultures taken during a period of cultures taken during a period of several days with temperature 101°F several days with temperature 101°F or higher or higher

Beware of negative culture due to Beware of negative culture due to recent antibiotic therapy.recent antibiotic therapy.

based on ≥2 cultures that are positive based on ≥2 cultures that are positive for the same organism.for the same organism.

casecase Male 60 years old came with feverMale 60 years old came with fever His H/C- strept. BovisHis H/C- strept. Bovis How to treat?How to treat?

Treat with antibioticTreat with antibiotic Colonoscope finds CA colonColonoscope finds CA colon

Prosthetic Heart Valves Prosthetic Heart Valves Early - caused by S. epidermidis, S. Early - caused by S. epidermidis, S.

aureus; also gram-negative bacteria, aureus; also gram-negative bacteria, fungi fungi

Late (>60 days postoperatively). Usually Late (>60 days postoperatively). Usually caused by streptococci., S. epidermidis caused by streptococci., S. epidermidis

Surgery is indicated if blood culture is Surgery is indicated if blood culture is still positive after 5 days of appropriate still positive after 5 days of appropriate antimicrobial therapy or recurrent antimicrobial therapy or recurrent infection infection

Syphilitic AortitisSyphilitic Aortitis Syphilitic aortitis is an obliterative Syphilitic aortitis is an obliterative

endarteritis of vasa vasorum of endarteritis of vasa vasorum of thoracic aorta that can lead to thoracic aorta that can lead to aneurysm formation.aneurysm formation.

Aortitis is the most common Aortitis is the most common expression of late syphilis expression of late syphilis

A positive treponemal test is seen in A positive treponemal test is seen in ~90% of cases.~90% of cases.

Behçet SyndromeBehçet Syndrome is a systemic vasculitis -a triad of is a systemic vasculitis -a triad of

recurrent aphthous ulcers of mouth recurrent aphthous ulcers of mouth and genitalia, and relapsing and genitalia, and relapsing panuveitis.panuveitis.

No definitive laboratory tests are No definitive laboratory tests are available.available.

Giant cell arteritis (GCA)Giant cell arteritis (GCA) is a systemic panarteritis of the is a systemic panarteritis of the

large and medium arteries, large and medium arteries, especially the carotid arteries.especially the carotid arteries.

affects the extracranial > the affects the extracranial > the intracranial arteries.intracranial arteries.

Biopsy of the involved segment of Biopsy of the involved segment of temporal artery is diagnostic temporal artery is diagnostic

The classic triad of increased ESR The classic triad of increased ESR (≥50 mm/h),anemia, and increased (≥50 mm/h),anemia, and increased serum ALP is strongly suggestive of serum ALP is strongly suggestive of GCAGCA

Laboratory findings reflecting Laboratory findings reflecting specific organ involvement specific organ involvement (Kidney ,CNS,Heart)(Kidney ,CNS,Heart)

Henoch-Schönlein Henoch-Schönlein PurpuraPurpura

is a hypersensitivity systemic vasculitis is a hypersensitivity systemic vasculitis of the small vessels with IgA deposition.of the small vessels with IgA deposition.

abdominal symptoms are predominantabdominal symptoms are predominant Diagnosis is made clinicallyDiagnosis is made clinically there are no pathognomonic laboratory there are no pathognomonic laboratory

findings. Coagulation tests are normal.findings. Coagulation tests are normal. Renal or skin biopsy supports the Renal or skin biopsy supports the

diagnosis; it will show focal segmental diagnosis; it will show focal segmental necrotizing GN that with IgA and C3 necrotizing GN that with IgA and C3 deposition.deposition.

Kawasaki Syndrome Kawasaki Syndrome (Mucocutaneous Lymph (Mucocutaneous Lymph

Node Syndrome)Node Syndrome)

is a variant of childhood polyarteritis is a variant of childhood polyarteritis of unknown etiology, with a high of unknown etiology, with a high incidence of coronary artery incidence of coronary artery complications. complications.

Diagnosis is confirmed by histologic Diagnosis is confirmed by histologic examination of the coronary artery examination of the coronary artery (same as polyarteritis nodosa)(same as polyarteritis nodosa)+Laboratory changes due to AMI.+Laboratory changes due to AMI.

Takayasu syndromeTakayasu syndrome is the term for granulomatous is the term for granulomatous

arteritis of the aorta.arteritis of the aorta. Diagnosis is established by Diagnosis is established by

characteristic arteriographic characteristic arteriographic changes or histologic changes or histologic examination examination

Thromboangiitis Obliterans Thromboangiitis Obliterans (Buerger Disease)(Buerger Disease)

is the vascular inflammation and is the vascular inflammation and occlusion of medium and small occlusion of medium and small arteries and veins of limbs; it is arteries and veins of limbs; it is related to smoking.related to smoking.

Histology shows characteristic Histology shows characteristic inflammatory and proliferative inflammatory and proliferative lesions lesions

Wegener Granulomatosis Wegener Granulomatosis (WG) (WG)

is a rare autoimmune systemic is a rare autoimmune systemic necrotizing or granulomatous necrotizing or granulomatous vasculitis most often affecting vasculitis most often affecting the respiratory tract and kidneys.the respiratory tract and kidneys.

c-ANCA is highly specific (>90%) c-ANCA is highly specific (>90%) for active WG. for active WG.

GIGI

Diarrhea -PMNDiarrhea -PMN Shigellosis,Salmonellosis,CampylobaShigellosis,Salmonellosis,Campyloba

cter,cter,Rotavirus,Invasive Escherichia coli Rotavirus,Invasive Escherichia coli

colitiscolitis Ulcerative colitisUlcerative colitis Pseudomembranous colitisPseudomembranous colitis

Diarrhea –no cellDiarrhea –no cell CholeraCholera Noninvasive E. coli diarrheaNoninvasive E. coli diarrhea Other bacterial toxins (e.g., Other bacterial toxins (e.g.,

Staphylococcus, Clostridium perfringens)Staphylococcus, Clostridium perfringens) Viral diarrheasViral diarrheas Parasitic infestations (e.g., G. lamblia, Parasitic infestations (e.g., G. lamblia,

Entamoeba histolytica, Dientamoeba Entamoeba histolytica, Dientamoeba fragilis)fragilis)

Drug relatedDrug related

Plummer-Vinson Plummer-Vinson Syndrome Syndrome

an iron-deficiency anemia associated an iron-deficiency anemia associated with dysphagia, atrophic gastritis, with dysphagia, atrophic gastritis, glossitis, etc glossitis, etc

increased risk of cancer of the increased risk of cancer of the esophagus esophagus

Pseudomembranous Pseudomembranous colitis colitis

is an antibiotic-related diarrhea and is an antibiotic-related diarrhea and colitis caused by C. difficile.colitis caused by C. difficile.

Tissue culture assay is gold standard Tissue culture assay is gold standard

Character of stool-?Character of stool-?

Enterocolitis, Necrotizing, Enterocolitis, Necrotizing, in Infancy in Infancy

a syndrome of acute intestinal necrosis a syndrome of acute intestinal necrosis of unknown etiology; it is especially of unknown etiology; it is especially associated with prematurity and associated with prematurity and exchange transfusions.exchange transfusions.

No specific laboratory tests are No specific laboratory tests are available.available.

Persistent metabolic acidosis, severe Persistent metabolic acidosis, severe hypoNa, and DIC are a common triad hypoNa, and DIC are a common triad in infants.in infants.

Infarction of the Infarction of the IntestineIntestine

Hematemesis, hematochezia, or melena Hematemesis, hematochezia, or melena are present in ~15% and occult blood in are present in ~15% and occult blood in <50% of cases. <50% of cases.

Caused byCaused by Primary (idiopathic)Primary (idiopathic) Secondary (~75% of cases) to:Secondary (~75% of cases) to:Emboli (SBE), nonbacterial valve Emboli (SBE), nonbacterial valve

vegetations, left atrium or ventricle, vegetations, left atrium or ventricle, atherosclerotic vascular disease,Venous atherosclerotic vascular disease,Venous thrombosisthrombosis

AscitesAscites blood-AF albumin gradient >1.1: portal blood-AF albumin gradient >1.1: portal

HTHT• • neutrophils count >250/µL is neutrophils count >250/µL is

presumptive of bacterial peritonitis.presumptive of bacterial peritonitis. Gram stain shows few bacteria in SBP Gram stain shows few bacteria in SBP

Culture sensitivity = 50% for SBP and Culture sensitivity = 50% for SBP and ~80% for secondary peritonitis ~80% for secondary peritonitis

• • TB acid-fast stain sensitivity = 20% to TB acid-fast stain sensitivity = 20% to 30% and TB culture sensitivity = 50% 30% and TB culture sensitivity = 50% to 70%.to 70%.

Chylous AscitesChylous Ascites Triglyceride is 2-8 × serum level. Triglyceride is 2-8 × serum level. Due toDue to

lymphatic obstruction (lymphoma or CA)lymphatic obstruction (lymphoma or CA)inflammation or obstruction of small inflammation or obstruction of small intestine trauma to chest or abdomen,intestine trauma to chest or abdomen,filariasis;filariasis; congenital lymphatic defects in pediatriccongenital lymphatic defects in pediatric

Abdominal TraumaAbdominal Trauma

Criteria to diagnose penetrating Criteria to diagnose penetrating abdominal wounds by peritoneal abdominal wounds by peritoneal lavage10,000 mL of normal saline 3 to lavage10,000 mL of normal saline 3 to 18 hours after injury : 18 hours after injury :

>10,000 RBC/µL (>5,000 RBC/µL for >10,000 RBC/µL (>5,000 RBC/µL for gunshot wounds)gunshot wounds)

Bacteria, fecal or vegetable matter on Bacteria, fecal or vegetable matter on Gram stain or bile Gram stain or bile

Occult BleedingOccult Bleeding guaiac -detect blood losses of ~20 mL/d. guaiac -detect blood losses of ~20 mL/d. Use of fecal sample obtained by digital Use of fecal sample obtained by digital

rectal exam is not recommended rectal exam is not recommended Stools may appear grossly normal with GI Stools may appear grossly normal with GI

bleeding of 100 mL/d.bleeding of 100 mL/d. Consistent melena requires 150 to 200 Consistent melena requires 150 to 200

mL blood in the stomachmL blood in the stomach False positive in FBC, animal blood foodFalse positive in FBC, animal blood food

RESP.RESP.

Croup or Croup or laryngotracheitislaryngotracheitis

inflammation of the upper airway inflammation of the upper airway below the glottis.below the glottis.

Caused byCaused byGroup B Haemophilus influenzae Group B Haemophilus influenzae

causes >90% of cases of epiglottitis; causes >90% of cases of epiglottitis; other bacteria include β-hemolytic other bacteria include β-hemolytic streptococci and pneumococci. streptococci and pneumococci.

PneumoniaPneumonia Prussian blue–nuclear red stain Prussian blue–nuclear red stain

strongly positive indicates severe strongly positive indicates severe alveolar hemorrhage alveolar hemorrhage

Pap smear- intranuclear inclusions Pap smear- intranuclear inclusions of herpes or CMV of herpes or CMV

Giemsa,GMS of sputum - PCPGiemsa,GMS of sputum - PCP

Pleural fluidPleural fluid Light criteria-exudate/transudateLight criteria-exudate/transudate1.LDH in fluid > 2/3 normal serum 1.LDH in fluid > 2/3 normal serum

LDHLDH2.Protein fluid/serum> 0.52.Protein fluid/serum> 0.53.LDH fluid/serum> 0.63.LDH fluid/serum> 0.6

4.Serum alb-fluid alb <1.24.Serum alb-fluid alb <1.2

Pleural fluidPleural fluid Nonpurulent fluid with positive Nonpurulent fluid with positive

Gram stain, positive blood culture, Gram stain, positive blood culture, or low pH suggests that effusion will or low pH suggests that effusion will become or behave like empyemabecome or behave like empyema

Streptococcus pneumoniaeStreptococcus pneumoniae causes causes parapneumonic effusions in 50% of parapneumonic effusions in 50% of cases, especially with positive blood cases, especially with positive blood culture culture

casecase Male 25 years old came with Male 25 years old came with

dyspneadyspnea CXR-left pleural effusionCXR-left pleural effusion Pleural tapping-WBC>50,000, high Pleural tapping-WBC>50,000, high

neutrophilsneutrophils

Need ICD?Need ICD?

No ICDNo ICD Indication for ICDIndication for ICD1.PH< 71.PH< 72.SUGAR<402.SUGAR<403.Frank pus3.Frank pus4.Gram stain /Culture +4.Gram stain /Culture +

pH <7.0 and glucose <40 mg/dL indicate pH <7.0 and glucose <40 mg/dL indicate need for ICD without grossly purulent need for ICD without grossly purulent fluid. fluid.

pH of 7.0–7.2 is a questionable indication pH of 7.0–7.2 is a questionable indication and should be repeated in 24 h, but ICD and should be repeated in 24 h, but ICD is favored if pleural fluid LD >1,000 IU/L. is favored if pleural fluid LD >1,000 IU/L.

ICD is also indicated if there is grossly ICD is also indicated if there is grossly purulent fluid or positive Gram stain or purulent fluid or positive Gram stain or culture. culture.

hemothoraxhemothorax hematocrit (Hct) >50% of peripheral hematocrit (Hct) >50% of peripheral

Hct indicates a hemothorax.Hct indicates a hemothorax. Cytology establishes the diagnosis in Cytology establishes the diagnosis in

approximately 50% of patients.approximately 50% of patients. Cytology plus biopsy is diagnostic in Cytology plus biopsy is diagnostic in

about 90% of cases about 90% of cases

Exudative effusionExudative effusion Caused byCaused by Pneumonia, malignancy, pulmonary Pneumonia, malignancy, pulmonary

embolism, and gastrointestinal embolism, and gastrointestinal conditions (especially pancreatitis conditions (especially pancreatitis and abdominal surgery) cause 90% and abdominal surgery) cause 90% of all exudates of all exudates

Pleural effusionPleural effusion Typically left-sided: Ruptured Typically left-sided: Ruptured

esophagus, acute pancreatitis, RA esophagus, acute pancreatitis, RA Typically right-sided or bilateral: Typically right-sided or bilateral:

Congestive heart failure (CHF) Congestive heart failure (CHF) Typically right-sided: Rupture of Typically right-sided: Rupture of

amebic liver abscess.amebic liver abscess.

ChylousChylous Chylous (milky) is usually due to Chylous (milky) is usually due to

trauma or obstruction of duct trauma or obstruction of duct PF triglycerides (TG) >110 mg/dL or PF triglycerides (TG) >110 mg/dL or

TG PF:serum ratio >2 occurs only in TG PF:serum ratio >2 occurs only in chylous effusion chylous effusion

pseudochylous effusionspseudochylous effusions Chylomicrons ≤50 mg/dL with Chylomicrons ≤50 mg/dL with

cholesterol >250 mg/dL.cholesterol >250 mg/dL.

AmylaseAmylase

Increased PF:serum ratio >1.0 Increased PF:serum ratio >1.0 Acute pancreatitis—may be normal Acute pancreatitis—may be normal

early with increase over timeearly with increase over time Also perforated esophageal rupture, Also perforated esophageal rupture,

peptic ulcer, necrosis of small peptic ulcer, necrosis of small intestine intestine

TB pleuraTB pleura Large mesothelial cells >5% are said Large mesothelial cells >5% are said

to rule out TB to rule out TB Acid-fast smears are positive in only Acid-fast smears are positive in only

<20% of TB pleurisy<20% of TB pleurisy Sensitivity >50% in TB. Cultures from Sensitivity >50% in TB. Cultures from

chest tubes chest tubes culture combined with histologic culture combined with histologic

examination establishes the diagnosis examination establishes the diagnosis in 95% of casesin 95% of cases

Adenosine deaminase >70 IU/L Adenosine deaminase >70 IU/L

Malignancy effusionMalignancy effusion

Cytology is positive in 60% of Cytology is positive in 60% of malignancies on first tap, 80% by malignancies on first tap, 80% by third tap. Is more sensitive than third tap. Is more sensitive than needle biopsyneedle biopsy

Combined cytology and pleural Combined cytology and pleural biopsy give positive results in 90%.biopsy give positive results in 90%.

Sputum examSputum exam Optimum specimen of sputum shows Optimum specimen of sputum shows

>25 PMNs and ≤5 squamous >25 PMNs and ≤5 squamous epithelial cells/LPF epithelial cells/LPF

Sensitivity of sputum culture is Sensitivity of sputum culture is estimated at 25% to 50%.estimated at 25% to 50%.

Carcinoma, BronchogenicCarcinoma, Bronchogenic Cytologic examination of sputum for Cytologic examination of sputum for

malignant cellsmalignant cells -positive in 40% of patients on first -positive in 40% of patients on first

samplesample -70% with three samples-70% with three samples -85% with five samples. -85% with five samples.

False-positive tests are <1%.False-positive tests are <1%.

CA lungCA lungClassified as:Classified as: Non-small cell lung carcinoma (NSCLC) Non-small cell lung carcinoma (NSCLC)

in 70% to 75% of casesin 70% to 75% of cases Squamous cell carcinoma (25%–30%)Squamous cell carcinoma (25%–30%) Adenocarcinoma (30%–35%)Adenocarcinoma (30%–35%) Large cell carcinoma (10%–15%)Large cell carcinoma (10%–15%) Small cell lung carcinoma (SCLC) in Small cell lung carcinoma (SCLC) in

20% to 25% of cases20% to 25% of cases Combined pattern in 5% to 10% of casesCombined pattern in 5% to 10% of cases

LE cells makes the diagnosis of SLELE cells makes the diagnosis of SLE CHF is typically bilateral; ≤20% are CHF is typically bilateral; ≤20% are

right-sided and ≤9% are left-sidedright-sided and ≤9% are left-sided

Plasma D-dimerPlasma D-dimer is a fibrin product generated by is a fibrin product generated by

action of plasmin on cross-linked action of plasmin on cross-linked fibrin molecules indicating that a fibrin molecules indicating that a clot has formedclot has formed

At cutoff level of 500 µg/L At cutoff level of 500 µg/L

Hepatobiliary Hepatobiliary

Total Serum Bilirubin Total Serum Bilirubin

Must exceed 2.5 mg/dL to produce Must exceed 2.5 mg/dL to produce clinical jaundiceclinical jaundice

Serum Bilirubin Serum Bilirubin (Conjugated:total)(Conjugated:total)

<20% conjugated<20% conjugated Constitutional (e.g., Gilbert disease, Crigler-Constitutional (e.g., Gilbert disease, Crigler-

Najjar syndrome)Najjar syndrome) Hemolytic statesHemolytic states

20% to 40% conjugated20% to 40% conjugated Favors Favors hepatocellular diseasehepatocellular disease rather than rather than

extrahepatic obstructionextrahepatic obstruction Disorders of bilirubin metabolism (e.g., Disorders of bilirubin metabolism (e.g.,

Dubin-Johnson, Rotor syndromes)Dubin-Johnson, Rotor syndromes) 40% to 60% conjugated: Occurs in either 40% to 60% conjugated: Occurs in either

hepatocellular or extrahepatic typehepatocellular or extrahepatic type >50% conjugated: Favors >50% conjugated: Favors extrahepatic extrahepatic

obstructionobstruction rather than hepatocellular disease rather than hepatocellular disease

ASTAST Half-life of AST is 18 hoursHalf-life of AST is 18 hours half-life of ALT is 48 hours. half-life of ALT is 48 hours. Thus, in early acute hepatitis, AST is Thus, in early acute hepatitis, AST is

usually higher initially, but by 48 usually higher initially, but by 48 hours, ALT is usually higher. hours, ALT is usually higher.

ALPALP

Increased ALP in liver diseases Increased ALP in liver diseases (due to increased synthesis from (due to increased synthesis from proliferating bile duct epithelium) proliferating bile duct epithelium) is the best indicator of biliary is the best indicator of biliary obstructionobstruction

High values (>5× normal) favor High values (>5× normal) favor obstructionobstruction

Isolated increase of GGT is a Isolated increase of GGT is a sensitive screening and sensitive screening and monitoring test for alcoholismmonitoring test for alcoholism

In cirrhosis with ascites, the kidney In cirrhosis with ascites, the kidney retains increased sodium and retains increased sodium and excessive water, causing dilutional excessive water, causing dilutional hyponatremia hyponatremia

Blood ammonia is increased in liver Blood ammonia is increased in liver coma and cirrhosis and with coma and cirrhosis and with portacaval shunting of blood.portacaval shunting of blood.

WBC is usually normal with active WBC is usually normal with active cirrhosis; increased (<50,000/µL) cirrhosis; increased (<50,000/µL) with massive necrosis, hemorrhage, with massive necrosis, hemorrhage, etc.; decreased with hypersplenism.etc.; decreased with hypersplenism.

Hep. encephalopathyHep. encephalopathy Blood ammonia is increased in 90% Blood ammonia is increased in 90%

of patients but does not reflect the of patients but does not reflect the degree of coma. Normal level in degree of coma. Normal level in comatose patient suggests another comatose patient suggests another cause of coma. Not reliable for cause of coma. Not reliable for diagnosis but may be useful to follow diagnosis but may be useful to follow individual individual

SBPSBP Spontaneous bacterial peritonitis—in Spontaneous bacterial peritonitis—in

10% to 30% of cirrhosis cases with 10% to 30% of cirrhosis cases with ascites. ascites.

70% have positive blood culture; 70% have positive blood culture; usually single organism, especially usually single organism, especially E. coli, pneumococcus, Klebsiella. E. coli, pneumococcus, Klebsiella.

≥≥250 PMNs/µL is diagnostic. 250 PMNs/µL is diagnostic.

AST:ALT ratio >1 associated with AST <300 AST:ALT ratio >1 associated with AST <300 U/L will identify 90% of patients with alcoholic U/L will identify 90% of patients with alcoholic liver disease; is particularly useful for liver disease; is particularly useful for differentiation from viral hepatitis, in which differentiation from viral hepatitis, in which increase of AST and ALT are about the same.increase of AST and ALT are about the same.

Anemia in >50% of patients may be macrocytic Anemia in >50% of patients may be macrocytic (folic acid or vitamin B12 deficiency), (folic acid or vitamin B12 deficiency), microcytic (iron deficiency), mixed, or microcytic (iron deficiency), mixed, or hemolytic.hemolytic.

In acute alcoholic hepatitis, GGT level is In acute alcoholic hepatitis, GGT level is usually higher than AST level. GGT is often usually higher than AST level. GGT is often abnormal in alcoholics even with normal liver abnormal in alcoholics even with normal liver histology. Is more useful as index of occult histology. Is more useful as index of occult alcoholism alcoholism

hepatitishepatitis Hepatitis, Chronic ActiveProgressive Hepatitis, Chronic ActiveProgressive

hepatitis >6 months duration of hepatitis >6 months duration of unknown etiology affecting patients of unknown etiology affecting patients of all ages possibly due to an external all ages possibly due to an external agent Due Toagent Due To

VirusesViruses HBV (with or without HDV)HBV (with or without HDV) HCV (with or without HGV)HCV (with or without HGV) CMV, others CMV, others

hepatitishepatitis MetabolicMetabolic Wilson diseaseWilson disease Alpha1-antitrypsin deficiencyAlpha1-antitrypsin deficiency HemochromatosisHemochromatosis Primary biliary cirrhosisPrimary biliary cirrhosis Sclerosing cholangitis Sclerosing cholangitis

hepatitishepatitis Drugs (e.g., methyldopa, Drugs (e.g., methyldopa,

nitrofurantoin, isonizid, nitrofurantoin, isonizid, oxyphenacetin) and chemicalsoxyphenacetin) and chemicals

Nonalcoholic fatty liverNonalcoholic fatty liver Alcoholic hepatitisAlcoholic hepatitis Autoimmune causes Autoimmune causes

Acute pancreatitisAcute pancreatitis Serum LipaseSerum Lipase Increases within 3 to 6 hours with Increases within 3 to 6 hours with

peak at 24 hours and usually returns peak at 24 hours and usually returns to normal over a period of 8 to 14 to normal over a period of 8 to 14 days. days.

Is superior to amylase; increases to a Is superior to amylase; increases to a greater extent and may remain greater extent and may remain elevated for up to 14 days after elevated for up to 14 days after amylase returns to normal.amylase returns to normal.

acute pancreatitisacute pancreatitis -In patients with signs of acute -In patients with signs of acute

pancreatitis, pancreatitis is highly pancreatitis, pancreatitis is highly likely (clinical specificity = 85%) when likely (clinical specificity = 85%) when lipase ≥5× URL, if values change lipase ≥5× URL, if values change significantly with time, and if amylase significantly with time, and if amylase and lipase changes are concordant. and lipase changes are concordant.

-Lipase should always be determined -Lipase should always be determined whenever amylase is determined. New whenever amylase is determined. New methodology improves clinical utility.methodology improves clinical utility.

It has been suggested that a It has been suggested that a lipase:amylase ratio >3 (and lipase:amylase ratio >3 (and especially >5) indicates alcoholic especially >5) indicates alcoholic rather than nonalcoholic rather than nonalcoholic pancreatitis).pancreatitis).

predisposing conditions of predisposing conditions of pancreatitispancreatitis

Alcohol abuse accounts ~36% of cases.Alcohol abuse accounts ~36% of cases. Biliary tract disease accounts 17% of cases.Biliary tract disease accounts 17% of cases. Idiopathic accounts >36% of cases.Idiopathic accounts >36% of cases. Infections (especially viral such as mumps and Infections (especially viral such as mumps and

coxsackie, CMV, AIDS)coxsackie, CMV, AIDS) Trauma and postoperative accounts >8% of casesTrauma and postoperative accounts >8% of cases Drugs (e.g., steroids, thiazides) >5% of cases.Drugs (e.g., steroids, thiazides) >5% of cases. Hypertriglyceridemia (Hyperlipidemia—Types V, I, Hypertriglyceridemia (Hyperlipidemia—Types V, I,

IV) 7% of casesIV) 7% of cases Hypercalcemia Hypercalcemia Tumors (pancreas, ampulla)Tumors (pancreas, ampulla) Anatomic abnormalities of ampullary region causing Anatomic abnormalities of ampullary region causing

obstruction obstruction HereditaryHereditary Renal failure; renal transplantationRenal failure; renal transplantation

Prognostic laboratory Prognostic laboratory findingsfindingsOn admissionOn admission

WBC >16,000/µLWBC >16,000/µL Blood glucose >200 mg/dLBlood glucose >200 mg/dL Serum LD >350 U/LSerum LD >350 U/L Serum AST >250 units/LSerum AST >250 units/L Age >55 yearsAge >55 years

Within 48 hoursWithin 48 hours >10% decrease in HCT>10% decrease in HCT Serum calcium <8.0 mg/dLSerum calcium <8.0 mg/dL Decrease in Hct >10 pointsDecrease in Hct >10 points Increase in BUN >5 mg/dLIncrease in BUN >5 mg/dL Arterial pO2 <60 mmHgArterial pO2 <60 mmHg Metabolic acidosis with base deficit >4 mEq/LMetabolic acidosis with base deficit >4 mEq/L

prognosisprognosis

Degree of amylase elevation has Degree of amylase elevation has no prognostic significanceno prognostic significance

CT scan, MRI, ultrasound are CT scan, MRI, ultrasound are useful for confirming diagnosis useful for confirming diagnosis or identifying causes or other or identifying causes or other conditionsconditions

CNSCNS

CSFCSF CSF -WBC may be corrected for CSF -WBC may be corrected for

presence of blood (e.g., traumatic presence of blood (e.g., traumatic tap, subarachnoid hemorrhage) by tap, subarachnoid hemorrhage) by subtracting 1 WBC for each 700 subtracting 1 WBC for each 700 RBCs/µL counted in CSF if the CBC RBCs/µL counted in CSF if the CBC is normal.is normal.

Neutrophilic leukocytes Neutrophilic leukocytes in CSFin CSF

are found in:are found in: Bacteria (e.g., Nocardia, Actinomyces, Bacteria (e.g., Nocardia, Actinomyces,

Arachnia, Brucella)Arachnia, Brucella) Fungal infections (Blastomyces, Fungal infections (Blastomyces,

Coccidioides, Candida, Aspergillus, Coccidioides, Candida, Aspergillus, Zygomycetes, Cladosporium, Zygomycetes, Cladosporium, Allescheria)Allescheria)

Chemical meningitisChemical meningitis Other conditions (e.g., SLE)Other conditions (e.g., SLE)

Lymphocytic cells in CSFLymphocytic cells in CSFare found in:are found in: Bacterial infections (e.g., Treponema Bacterial infections (e.g., Treponema

pallidum, Leptospira,, Borrelia burgdorferi pallidum, Leptospira,, Borrelia burgdorferi [Lyme disease], M. tuberculosis)[Lyme disease], M. tuberculosis)

Fungal infections (e.g., Cryptococcus Fungal infections (e.g., Cryptococcus neoformans, Candida species, Coccidioides neoformans, Candida species, Coccidioides immitis, Histoplasma capsulatum, immitis, Histoplasma capsulatum, Blastomyces dermatitides)Blastomyces dermatitides)

Parasitic diseases (e.g., toxoplasmosis, Parasitic diseases (e.g., toxoplasmosis, cysticercosis)cysticercosis)

Viral infections (e.g., mumps, lymphocytic Viral infections (e.g., mumps, lymphocytic choriomeningitis). Atypical lymphocytes may choriomeningitis). Atypical lymphocytes may be seen in EBV infection and less often in be seen in EBV infection and less often in CMV or HSV infection.CMV or HSV infection.

Parameningeal disorders (e.g., brain abscess)Parameningeal disorders (e.g., brain abscess) Noninfectious disorders (e.g., neoplasms, Noninfectious disorders (e.g., neoplasms,

sarcoidosis, multiple sclerosis, granulomatous sarcoidosis, multiple sclerosis, granulomatous arteritis)arteritis)

Eosinophils In CSFEosinophils In CSFbe found in:be found in: LymphomaLymphoma Helminth infection (e.g., Helminth infection (e.g.,

angiostrongyliasis, cysticercosis)angiostrongyliasis, cysticercosis) Rarely, other infections (e.g., TB, Rarely, other infections (e.g., TB,

syphilis, Rocky Mountain spotted fever, syphilis, Rocky Mountain spotted fever, coccidioidomycosis)coccidioidomycosis)

Eo>5% may indicate malfunction or Eo>5% may indicate malfunction or infection of a ventriculoperitoneal infection of a ventriculoperitoneal shuntshunt

Multiple Sclerosis (MS)Multiple Sclerosis (MS) CSF changes are found in >90% of CSF changes are found in >90% of

MS patients. Oligoclonal IgG bands MS patients. Oligoclonal IgG bands or elevated IgG index are the 2 CSF or elevated IgG index are the 2 CSF findings recognized as positive.findings recognized as positive.

musculoskeletalmusculoskeletal

Serum Enzymes in Diseases Serum Enzymes in Diseases of Muscleof Muscle

Creatine kinase (CK) is the test of choice. It is Creatine kinase (CK) is the test of choice. It is more specific and sensitive than AST and LD and more specific and sensitive than AST and LD and more discriminating than aldolase (ALD) but AST more discriminating than aldolase (ALD) but AST is more significantly associated with inflammatory is more significantly associated with inflammatory myopathy and more useful in these casesmyopathy and more useful in these cases

Increased InIncreased In PolymyositisPolymyositis Muscular dystrophyMuscular dystrophy Myotonic dystrophyMyotonic dystrophy Some metabolic disordersSome metabolic disorders Malignant hyperthermiaMalignant hyperthermia Prolonged exercise; peak 24 hours after extreme Prolonged exercise; peak 24 hours after extreme

exercise (e.g., marathon); smaller increases in exercise (e.g., marathon); smaller increases in well-conditioned athleteswell-conditioned athletes

Wilms tumors with rhabdomyomatous features Wilms tumors with rhabdomyomatous features (CK-MB may also be increased (CK-MB may also be increased

HyperthyroidismHyperthyroidism

Normal serum M.enzyme levelsNormal serum M.enzyme levels Increased urine creatine; Increased urine creatine;

decreased creatine tolerancedecreased creatine tolerance Normal muscle biopsy findingsNormal muscle biopsy findings Causes some cases of Causes some cases of

hypokalemic periodic paralysishypokalemic periodic paralysis

Malignant HyperthermiaMalignant Hyperthermia Rare autosomal dominant hypermetabolic Rare autosomal dominant hypermetabolic

syndrome syndrome causing abnormally increased release of causing abnormally increased release of

calcium from membrane of sarcoplasmic calcium from membrane of sarcoplasmic reticulumreticulum

triggered by various inhalational [e.g., ether] triggered by various inhalational [e.g., ether] and local anesthetic agents, muscle relaxants and local anesthetic agents, muscle relaxants [e.g., succinylcholine, tubocurarine][e.g., succinylcholine, tubocurarine]

causing hyperthermia, muscle rigidity, and causing hyperthermia, muscle rigidity, and 70% fatality70% fatality

Combined metabolic and respiratory acidosis Combined metabolic and respiratory acidosis is the most consistent abnormality and is is the most consistent abnormality and is diagnostic in the presence of muscle rigidity or diagnostic in the presence of muscle rigidity or rising temperature. pH is often <7.2, BE >-10, rising temperature. pH is often <7.2, BE >-10, hypoxia, and arterial pCO2 of 70 to 120 torr. hypoxia, and arterial pCO2 of 70 to 120 torr. Immediate arterial blood gas analysis should Immediate arterial blood gas analysis should be performed.be performed.

Myopathy Associated with Myopathy Associated with AlcoholismAlcoholism

Acute (necrotizing)Acute (necrotizing) Increased serum CK, AST, and other Increased serum CK, AST, and other

enzymes.enzymes. Serum CK increased in 80% of Serum CK increased in 80% of

patients; rises in 1 to 2 days; reaches patients; rises in 1 to 2 days; reaches peak in 4 to 5 days; lasts ~2 weeks. peak in 4 to 5 days; lasts ~2 weeks.

Gross myoglobinuriaGross myoglobinuria Acute renal failureAcute renal failure

Myopathy Associated with Myopathy Associated with AlcoholismAlcoholism

Chronic Chronic :: Increased serum CK in 60% of patients to Increased serum CK in 60% of patients to

average of 2× ULNaverage of 2× ULN Increased AST and other enzymes due to Increased AST and other enzymes due to

liver as well as muscle changesliver as well as muscle changes Increased urine creatineIncreased urine creatine Diminished ability to increase blood lactic Diminished ability to increase blood lactic

acid with ischemic exerciseacid with ischemic exercise Abnormalities on muscle biopsy (support the Abnormalities on muscle biopsy (support the

diagnosis)diagnosis) MyoglobinuriaMyoglobinuria

Infective ArthritisInfective Arthritis BacterialBacterial

In purulent arthritis, organism is recovered In purulent arthritis, organism is recovered from joint in 90% of patients and from blood from joint in 90% of patients and from blood in 50% of patients. Most often due to S. in 50% of patients. Most often due to S. aureus (60%) and Streptococcus species.aureus (60%) and Streptococcus species.

Gram stain is positive in ~50% of patients; it Gram stain is positive in ~50% of patients; it is particularly useful for establishing is particularly useful for establishing diagnosis promptly and in cases in which diagnosis promptly and in cases in which cultures are negative.cultures are negative.

Culture may be negative because of prior Culture may be negative because of prior administration of antibiotics.administration of antibiotics.

In children, most common organisms are H. In children, most common organisms are H. influenzae type b, S. aureus, various influenzae type b, S. aureus, various streptococci, and gram-negative bacilli.streptococci, and gram-negative bacilli.

In young adults, >50% of cases are due to In young adults, >50% of cases are due to Neisseria gonorrhoeae; rest are due to S. Neisseria gonorrhoeae; rest are due to S. aureus, streptococci, or gram-negative bacilli.aureus, streptococci, or gram-negative bacilli.

TB arthritisTB arthritis Gram stain and bacterial Gram stain and bacterial

cultures are negativecultures are negative but acid-fast stain, but acid-fast stain,

culture, and biopsy of culture, and biopsy of synovia confirm the synovia confirm the diagnosisdiagnosis

Myasthenia Gravis (MG)Myasthenia Gravis (MG) Acetylcholine Receptor (AChR) Acetylcholine Receptor (AChR)

Binding Antibodies is the standard Binding Antibodies is the standard assay and should be ordered first:assay and should be ordered first: Negative in ≤34% of patients with MGNegative in ≤34% of patients with MG Negative ≤50% of patients with ocular Negative ≤50% of patients with ocular

MGMG May be negative in first 6–12 monthsMay be negative in first 6–12 months

Crystalline Crystalline ArthropathyChondrocalcinoArthropathyChondrocalcino

sis (“Pseudogout”)sis (“Pseudogout”) Inflammatory mono- or polyarticular Inflammatory mono- or polyarticular

arthritis due to deposition of calcium arthritis due to deposition of calcium pyrophosphate dehydrate crystals in pyrophosphate dehydrate crystals in jointsjoints

Joint fluid contains crystals identified as Joint fluid contains crystals identified as calcium pyrophosphate dehydrate, inside calcium pyrophosphate dehydrate, inside and outside of WBCs, and macrophages and outside of WBCs, and macrophages that are differentiated from urate crystals that are differentiated from urate crystals under polarized light, which under polarized light, which distinguishes them from gout. distinguishes them from gout.

Crystals may also be identified by other Crystals may also be identified by other means (e.g., chemical, x-ray diffraction).means (e.g., chemical, x-ray diffraction).

GoutGout

Group of disorders of purine Group of disorders of purine metabolism characterized by metabolism characterized by monosodium urate crystal deposits monosodium urate crystal deposits in joints and soft tissuesin joints and soft tissues

episodes of acute inflammatory episodes of acute inflammatory arthritis [response to crystal arthritis [response to crystal deposits], and hyperuricemia. deposits], and hyperuricemia.

Most uric acid is synthesized in Most uric acid is synthesized in liver and intestinal mucosa. liver and intestinal mucosa.

Two thirds excreted by kidney; one Two thirds excreted by kidney; one third excreted by bowel.third excreted by bowel.

GoutGout Primary (i.e., inborn) (30% of patients)Primary (i.e., inborn) (30% of patients)-Idiopathic-Idiopathic-Increased purine biosynthesis (Lesch-Nyhan syndrome)-Increased purine biosynthesis (Lesch-Nyhan syndrome) Secondary (70% of patients)Secondary (70% of patients)

1.1.Overproduction (10% of secondary cases); Overproduction (10% of secondary cases); overexcreters: >750 to 1,000 mg/day of uric acidoverexcreters: >750 to 1,000 mg/day of uric acid Neoplastic and hemolytic conditionsNeoplastic and hemolytic conditions 2.Increased breakdown of adenosine 2.Increased breakdown of adenosine triphosphatetriphosphate

Glycogen storage diseases (I, III, V, VII)Glycogen storage diseases (I, III, V, VII) Alcohol ingestionAlcohol ingestion Myocardial infarctionMyocardial infarction

3.3.Decreased renal function (90% of secondary cases); Decreased renal function (90% of secondary cases); underexcreters: <700 mg/day of uric acidunderexcreters: <700 mg/day of uric acid

GoutGout Diagnostic Criteria: Diagnostic Criteria: -Presence of crystals of monosodium -Presence of crystals of monosodium

urate from tophi or joint fluid viewed urate from tophi or joint fluid viewed microscopically under polarized lightmicroscopically under polarized light

-strongly negative birefringent needle--strongly negative birefringent needle-shaped crystals both inside and outside shaped crystals both inside and outside PMNs or macrophagesPMNs or macrophages

-differentiates it from pseudogout. -differentiates it from pseudogout. (Found in synovial fluid in 75% of (Found in synovial fluid in 75% of

patients between attacks.)patients between attacks.)

hematohemato

Macrocytic anemiasMacrocytic anemias Macrocytic anemias (MCV >95 fL and often >110 fL; Macrocytic anemias (MCV >95 fL and often >110 fL;

MCHC >30 g/dL)MCHC >30 g/dL) Megaloblastic anemiasMegaloblastic anemias PA (vitamin B12 or folate deficiency)PA (vitamin B12 or folate deficiency) Sprue (e.g., steatorrhea, celiac disease, intestinal resection or Sprue (e.g., steatorrhea, celiac disease, intestinal resection or

fistula)fistula) Macrocytic anemia of pregnancyMacrocytic anemia of pregnancy AlcoholismAlcoholism Liver diseaseLiver disease Anemia of hypothyroidismAnemia of hypothyroidism Carcinoma of stomach, following total gastrectomyCarcinoma of stomach, following total gastrectomy Drugs:Drugs:

Oral contraceptivesOral contraceptives Anticonvulsants (e.g., phenytoin, primidone, phenobarbital)Anticonvulsants (e.g., phenytoin, primidone, phenobarbital) Antitumor agents (e.g., methotrexate, hydroxyurea, Antitumor agents (e.g., methotrexate, hydroxyurea,

cyclophosphamide)cyclophosphamide) Antimicrobials (e.g., sulfamethoxazole, sulfasalazine, Antimicrobials (e.g., sulfamethoxazole, sulfasalazine,

trimethoprim, zidovu-dine, pyrimethamine trimethoprim, zidovu-dine, pyrimethamine

Normocytic anemiasNormocytic anemiasNormocytic anemias (MCV = 80–94 Normocytic anemias (MCV = 80–94

fL; MCHC >30 g/dL)fL; MCHC >30 g/dL) Following acute hemorrhageFollowing acute hemorrhage Some hemolytic anemiasSome hemolytic anemias Some hemoglobinopathiesSome hemoglobinopathies Anemias due to inadequate blood Anemias due to inadequate blood

formationformation

casecase 50 years old male came with pale50 years old male came with pale BPBPนัง่นัง่= 120/70,= 120/70,นอน นอน 130/80130/80 Hct=25, MCV=80Hct=25, MCV=80

What is the cause of anemia?What is the cause of anemia?

AnswerAnswer

UGIHUGIH

Microcytic anemiasMicrocytic anemiasMicrocytic anemias (MCV <80 fL; Microcytic anemias (MCV <80 fL;

MCHC <30 g/dL)MCHC <30 g/dL) Usually hypochromicUsually hypochromic

Iron-deficiency anemia, e.g.,Iron-deficiency anemia, e.g., Inadequate intakeInadequate intake Poor absorptionPoor absorption Excessive iron requirementsExcessive iron requirements Chronic blood lossChronic blood loss

Pyridoxine-responsive anemiaPyridoxine-responsive anemia Thalassemia Thalassemia Lead poisoningLead poisoning Anemia of chronic diseases Anemia of chronic diseases Disorders of porphyrin synthesisDisorders of porphyrin synthesis

summarysummary KidneyKidney CardioCardio GIGI RespirationRespiration HepatobiliaryHepatobiliary CNSCNS musculoskeletalmusculoskeletal HematoHemato

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FerritinFerritin Ferritin is an acute-phase reactant and thus is Ferritin is an acute-phase reactant and thus is

increased in many patients with:increased in many patients with:- various acute and chronic liver diseasesvarious acute and chronic liver diseases- alcoholism (declines during abstinence)alcoholism (declines during abstinence)- malignancies (e.g., leukemia, Hodgkin malignancies (e.g., leukemia, Hodgkin

disease)disease)- infection and inflammation infection and inflammation - hyperthyroidismhyperthyroidism Serum ferritin may not be decreased when Serum ferritin may not be decreased when

iron deficiency coexists with these conditions; iron deficiency coexists with these conditions; in such cases, bone marrow stain for iron may in such cases, bone marrow stain for iron may be the only way to detect the iron deficiency.be the only way to detect the iron deficiency.

Iron overloadIron overload Iron overload (e.g., hemosiderosis, idiopathic Iron overload (e.g., hemosiderosis, idiopathic

hemochromatosis). hemochromatosis). Can be used to monitor therapeutic removal Can be used to monitor therapeutic removal

of excess storage iron. Transferrin saturation of excess storage iron. Transferrin saturation is more sensitive to detect early iron overload is more sensitive to detect early iron overload in hemochromatosisin hemochromatosis

serum ferritin is used to confirm diagnosis serum ferritin is used to confirm diagnosis and as indication to proceed with liver biopsy. and as indication to proceed with liver biopsy.

Ratio of serum ferritin (in ng/mL) to alanine Ratio of serum ferritin (in ng/mL) to alanine aminotransferase (ALT) (in IU/L) >10 in iron-aminotransferase (ALT) (in IU/L) >10 in iron-overloaded thalassemic patients but averages overloaded thalassemic patients but averages ≤2 in viral hepatitis; ratio decreases with ≤2 in viral hepatitis; ratio decreases with successful iron chelation therapy.successful iron chelation therapy.

TIBCTIBC Iron-Binding Capacity, Total SerumTIBC (in µmol/L) is obtained by Iron-Binding Capacity, Total SerumTIBC (in µmol/L) is obtained by

the following equation: transferrin (mg/L) × 0.025.the following equation: transferrin (mg/L) × 0.025. Unsaturated iron-binding capacity = TIBC minus serum iron (µg/dL).Unsaturated iron-binding capacity = TIBC minus serum iron (µg/dL). Use inUse in1.Differential diagnosis of anemias1.Differential diagnosis of anemias2.Should always be performed whenever serum iron is done to calculate 2.Should always be performed whenever serum iron is done to calculate

percent saturation (see percent saturation (see Fig 11-2Fig 11-2) for diagnosis of iron deficiency) for diagnosis of iron deficiency3.Screening for iron overload3.Screening for iron overload Increased InIncreased In-Iron deficiency-Iron deficiency-Acute and chronic blood loss-Acute and chronic blood loss-Acute liver damage-Acute liver damage-Late pregnancy-Late pregnancy Decreased InDecreased In-Hemochromatosis-Hemochromatosis-Cirrhosis of the liver-Cirrhosis of the liver-Thalassemia-Thalassemia-Anemias of infection and chronic diseases (e.g., uremia, RA, some -Anemias of infection and chronic diseases (e.g., uremia, RA, some

neoplasms neoplasms

SerumTransferrinSerumTransferrin Transferrin, transports circulating Fe3 molecules.Transferrin, transports circulating Fe3 molecules. Normally only about 1/3 of iron-binding sites are Normally only about 1/3 of iron-binding sites are

occupied; the remainder is called unsaturated iron-occupied; the remainder is called unsaturated iron-binding capacity.binding capacity.

Increased InIncreased In-Iron-deficiency anemia; is inversely proportional to iron -Iron-deficiency anemia; is inversely proportional to iron

storesstores-Pregnancy, estrogen therapy, hyperestrogenism-Pregnancy, estrogen therapy, hyperestrogenism Decreased InDecreased In-Hypochromic microcytic anemia of chronic disease-Hypochromic microcytic anemia of chronic disease-Acute inflammation-Acute inflammation-Protein deficiency or loss (e.g., burns, chronic -Protein deficiency or loss (e.g., burns, chronic

infections, chronic diseases [e.g., various liver and infections, chronic diseases [e.g., various liver and kidney diseases, neoplasms]), nephrosis, malnutrition)kidney diseases, neoplasms]), nephrosis, malnutrition)

-Genetic deficiency-Genetic deficiency

Transferrin SaturationTransferrin Saturation Serum transferrin saturation is obtained by Serum transferrin saturation is obtained by

serum iron / TIBCserum iron / TIBC normal 20% to 50%. normal 20% to 50%. Use in Differential diagnosis of anemias/ Use in Differential diagnosis of anemias/

Screening for hereditary hemochromatosisScreening for hereditary hemochromatosis Increased InIncreased In-Hemochromatosis-Hemochromatosis-Hemosiderosis-Hemosiderosis-Thalassemia-Thalassemia-Birth control pills (≤75%)-Birth control pills (≤75%)-Ingestion of iron (≤100%)-Ingestion of iron (≤100%)-Iron dextran administration causes increase -Iron dextran administration causes increase

for several weeks (may be >100%)for several weeks (may be >100%)