Lab Interpretation Michael Nelson MD

7/22/2015

Overview Broad topic

Impossible to be all encompassing

Focus on Emergency Medicine tests

Try to cover interpretation and application

Common Labs CBC w/ diff

BMP

LFTs

Lipase

Cardiac Markers

ESR/CRP

D-dimer

CPK

Lactate

Cultures

CBC WBC

Hgb

Plts

WBC - Neutropenia Decreased production by marrow

Aplastic Anemia

Cancer

Congenital

Radiation

Decrease B12, Folate, copper

Meds: Phenytoin, PTU, Indocin, Clozapine, Bactrim, Felcainide, Chlorpromazine, APDs

Increased destruction of cells: autoimmune, chemorx

Infections: viral, severe sepsis

Sequestration - Hemodialysis

Leukocytosis Five cell lines: Neutros, Eosinos, Basos, Monos, Lymphos

Left shift: increase in immature cells (Bands, metamyelos)

Right shift: increase in mature cells (giant cells) Suppression of bone marrow

Pernicious anemia, radiation sickness

Leukamoid reaction = WBC > 50000 Normally response to underlying condition

Increase in ALP (decrease in ALP with CML)

Leukocytosis Neutrophilia

Bacterial infections, burns, AMI, tissue necrosis

Eosinophilia Parasites, Allergic reaction, SLE, some cancers

Basophilia CML

Monocytosis Chronic infections (TB, Malaria), IBD, SLE

Lymphocytosis Viral infections, chronic infections (TB, Brucellosis, Pertussis), CLL

Other: Steroids, B-agonists, Lithium

Anemia Blood loss

Trauma, GI bleed

Decreased production Fe deficiency, B12/Folate deficiency, thalessemia, cancer, aplastic anemia, CKD

Increased breakdown HgbSS, malaraia, genetic (PK, G6PDH), Warm Ab, Cold agglutin, TTP/DIC

Transfusion

Transfusion S

Polycythemia Hct > 55%

Increased production: chronic low O2 (COPD), MPD, Altitude, genetic, cancer, EPO

Relative Increased hgb: dehydration, stress, burns

Risks: HTN, Thrombosis

Treatment: Phlebotomy!

Thrombocytopenia Plts < 150000

Plts < 50000: bruising with minor trauma

Plts 15 – 30000: spontaneous bruising/bleeding

Purpura/Petechia

Thrombocytopenia Decreased production

Aplastic anemia, MDS, Leukemia, sepsis, Folate/B12 deficiency, dehydration, hereditary (Fanconi, Alport, etc), Dengue

Increased destruction ITP, TTP, HUS, DIC, APA/SLE, Dengue, PNH, Splenic sequestration

Medication induced VPA, MTX, HIT, PPI, H2 antagonists, isotretinoin, IFN

Other Snakebite (Crotalids), Lyme, Niacin toxicity

Thrombocytosis Plts > 450000

Often occurs with inflammatory process (thrombopoetin is acute phase reactant)

Plts > 750000 concerning

Symptoms: erythromelalgia, thrombosis

Essential: myeloproliferative disease, CML, polycythemia

Reactive: inflammation, surgery, splenectomy/asplenia, anemia, IBD, RA, infections

Hyponatremia Na < 135 mEq/L

Severe: Na < 125

Clinical: N/V, HA, confusion, lethargy, loss of appetite, weakness, cramps, Sz, coma

Mild hyponatremia (131 – 135) associated with falls, decreased attention in elderly, increased adverse events in elderly

Most important is “the delta”

Hyponatremia Hypovolemic

V/D, diuretics, Addison’s, CAH

Euvolemic SIADH, hypothyroid, brain damage

Hypervolemic CHF, cirrhosis, CKD/nephrotic, edema

Other Polydipsia, Beer potomania, factitious (HyperGlc, HyperTG, Elevated IG in MM)

Hypernatremia Na > 145 mEq/L

Normally from free water deficit/dehydration

Clinical: lethargy, weakness, irritable, edema, cramps, Sz, coma

Hypovolemic: sweating, diarrhea, decreased po intake

Euvolemic: DI

Hypervolemic: rare, excessive salt intake (mostly kids)

Hypokalemia K < 3.5 mEq/L

Clinical: Increased BP, weakness, myalgias, cramping, tremor, constipation, paralytic ileus, paralysis, rhabdo, U waves on EKG

Hypokalemia - Causes Decreased K intake

GI loss: diarrhea, pancreatic fistula

Sweating

Urinary loss: diuretics, caffeine, hyperaldosterone (Conn’s, RAS, Cushings, excessive licorice intake - glycrrhizin)

Shift: acidosis, insulin, beta agonists, EPI

Hypomagnesemia

Hyperkalemia K > 5 mEq/L

Clinical: malaise, weakness, palpitations, sudden cardiac death

Decreased elimination CKD, ACE-I/ARBs, NSAIDs, Trimethoprim, K sparing diuretics, Addison’s, RTA IV

Release from cells Rhabdo, burns, hemolysis, digoxin, succinylcholine, box jellyfish

Excessive intake

EKG changes Normal

Peaked T wave

PR prolongation

Loss of P wave

QRS widening

Sine wave

Goldfrank’s Toxicologic Emergencies, 12th edition

EKG changes

http://wesleytodd.blogspot.com/2013/06/lytes.html

Cl and HCO3 Hypochloremia: usually from hypoNa or HyperHCO3

HyperCl: excess NaCl, fluid loss (V/D), RTA I/II, hypoNa, DM

HCO3: rough evaluation of acid/base Low: acidosis

High: alkalosis

BUN/Cr BUN: reabsorbed by tubules, regulated; normal 5 - 20

Cr: reabsorption remains relatively constant; 0.6 – 1.2

BUN:Cr > 20:1 Prerenal (dehydration/hypoperfusion)

BUN:Cr = 10 – 20:1 Normal/Postrenal

BUN:Cr < 10:1 Intrarenal (reduced reabsortion BUN)

Elevated BUN in GI bleed (ratio of > 30:1 highly specific in kids)

Jaffe reaction

Hypoglycemia Clinical: confusion, shaky, clumsiness, LOC, Sz

Meds: insulin, SFU

CKD, insulinomas, liver disease, hypothyroid, starvation, severe infection, alcohol, Ackee fruit (hypoglycin)

Hyperglycemia Clinical: polydipsia, polyphagia, polyuria, weight loss, blurred vision, fatigue, dry mouth/skin, Coma

DKA vs HHS

Causes: DM, steroids, octreotide, Beta blockers, EPI, Hctz, stimulants acutely, APDs (olanzapine, duloxetine), acute stress/critical illness (AMI, CVA, sepsis)

Others: thyroid, adrenal, pituitary disorders, pancreatic failure, intracranial disease (encephalitis, ICH, meningitis), seizures

DKA vs HHS

Pathogenesis

LFTs AST (SGOT), ALT (SGPT), GGT, ALP, Bili, PT/PTT, Albumin

AST: present in liver, RBCs, cardiac, skeletal muscle

ALT: more liver specific

AST/ALT > 1000: APAP, shock, fulminant hepatic failure

AST/ALT > 3x: etoh, hepatitis, sepsis, cancer, autoimmune, steatohepatitis, rhabdomyolysis, Wilsons, drug induced

LFTs ALP: in cells of biliary tract, bone, placental tissue

Cholestasis, obstruction, infiltrative disease, mets to bone, growing children, third trimester pregnancy

Direct Bilirubin Obstruction, hepatitis, cancer, cirrhosis

Indirect Bilirubin Hemolysis, internal hemorrhage

GGT: reasonably liver specific Cholestasis

Lipase/Amylase Enzyme catalyzes fat hydrolysis, digest starches

Lipase more pancreas specific than amylase

2x upper limit normal has higher specificity for pancreatitis

Amylase found in salivary glands Trauma

Choledocholithiasis

Ascites

Cardiac tests Troponin: most sensitive, most specific

TnI/TnT have cardiac specific isoforms

CK-MB: 4-6 hours post event, peak 24 hours

LDH: nonspecific

AST: nonspecific

Mgb: first to rise 2 – 4 hours, peak hours, nonspecific

BNP

Cardiac tests S

Troponin Elevated trop = relatively 4 fold risk adverse cardiac events

Increased mortality in CHF and CKD

10 fold risk in PE

Troponin

ACS

Post cardiac surgery/post PCI

PE

ESRD

Pericarditis/myocarditis

Dissection (particularly Type A)

CHF

Strenuous exercise

Rhabdomyolysis

Cardiac contusion/BCI

Amyloidosis/Infiltrative disease

Chemotherapy Doxirubicin Cyclophosphamide Paclitaxil

Hemolysis

BNP Secreted in response to wall stress/volume overload

Double mortality rate with elevated trop and BNP

Useful for ambiguous dyspnea

ESR/CRP Acute phase reactants

Cytokines induce CRP synthesis in liver

CRP has constant clearance rate, independent of physical properties

Normal CRP < 10 mg/L

Increase 4 – 6 hours after tissue injury

Remains elevated during acute phase response

ESR/CRP ESR value affected by size/shape of RBCs, fluid status, age

Affected by temperature, pregnancy, smoking, drugs (NSAIDs and steroids decrease ESR)

ESR/CRP Inflammation

Pregnancy

Anemia

Autoimmune disorders (SLE, RA, TA, PMR, IBD)

Infections

Cancer (MM, lymphoma)

CKD

Clinical use in ED Septic arthritis

Spinal epidural abscess

Specific inflammatory conditions (mostly TA)

CRP better predictor in post surgical patients for infection rather than fever, WBC, or ESR

Negative CRP = negative infection

Septic arthritis

Can rule in

Can’t rule out

Kocker criteria Septic arthritis vs transient synovitis in kids with hip pain

NWB

ESR > 40

WBC > 12

Fever > 38.5

SEA

Can help rule in

Can’t rule out

CRP almost always elevated

Even MRI needs to be repeated

Temporal arteritis Usually ESR > 50, can be > 100

Can be normal in 7 – 20% of patients

CRP higher sensitivity and specificity (98% and 76%) vs ESR

Can have nonconcordance between ESR and CRP

D-dimer Breakdown of fibrin split products

Elevated in Thrombosis Pregnancy DIC Liver disease Inflammation Malignancy Trauma Surgery Age (age > 50: age x 10 ug/L)

If low pre-test probability for thrombosis, negative D-dimer helps “rule out” probability of thrombosis

CPK Elevated

AMI

Rhabdomyolysis

Muscular dystrophy

Autoimmune myositis

CKD

CK levels 5x upper limit suggest rhabdo, level < 20000 low risk for renal issues (no level that will get ARF)

Lactate

Lactic acid Tissue ischemia

AMI, Bowel necrosis, muscle necrosis, shock

Infection

DKA

Hypoxia

Hepatic disease

Lymphoma

Excessive ethanol

Drugs: Metformin, INH, NRTIs, CN

Genetic: Frc 1,6 diphtase deficiency, Glc-6-phtase deficiency, MELAS, Pyruvate Dhase deficiency

Lactate

Lactate non-clearance mortality = 60%

Lactate clearance mortality = 19%

Conclusion Most emergency labs are not definitive

Multiple etiologies for “positive” labs

Depends on clinical scenario with interpretation of labs

Many have risk stratification implications