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Home , Anion gap, CSF glucose, Diabetes insipidus

11/12/15

Some things you should When lab tests are useful know about laboratory 1. Managing patients during critical care tests…But maybe you transports don’t 2. While transporting patient to medical facilities for evaluation of laboratory Steve Faynor, CCEMT-P abnormalities HCA Chippenham Medical Center Richmond Ambulance Authority

Objectives

1. Review some basic laboratory tests. Treat the patient, not the 2. Appreciate how patterns of laboratory test results can offer insight into etiology. laboratory values. 3. Learn how laboratory test calculations can add additional clinical information. 4. Review some limitations of laboratory tests.

ELECTROLYTES & A case of “bad labs” RENAL FUNCTION TESTS

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Hypernatremia & Renal Failure • 89 year old white female • Hyperaldosteronism • Coming from nursing home due to • Cushing’s or syndrome abnormal labs • insipidus (deficiency of ADH) • 172 mmol/L • • 4.2 mmol/L • 137 mmol/L • Carbon dioxide 21 mmol/L • What are some causes of hypernatremia?

• BP 122/66, SBP 99 later • BUN 212 mg N/dL • HR 64/min • 6.10 mg/dL • RR 21/min • What do these values indicate?

• SpCO2 98% on 4 L oxygen per min • Does this change your therapy? • Tongue dry, skin turgor poor • What is the cause of the hypernatremia in this patient? Treatment?

Acute Renal Failure Use of the BUN/creatinine ratio • Intrinsic renal disease • In intrinsic causes of acute renal failure, the – : ischemia, toxins BUN/creatinine ratio is typically 10-15. – Acute glomerulonephritis • In pre-renal causes of acute renal failure, – CKD with missed dialysis the BUN/creatinine ratio is typically >20. • Post-renal • In this case, the BUN/creatinine ratio was – Obstruction: stone, tumor, enlarged prostate 34.8. • Pre-renal • Do you want to stick with the same – Dehydration, , heart failure treatment?

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Creatinine Creatinine Clearance

• About 50% of the must be • Calculated from the 24-hr creatinine, destroyed before the creatinine rises urine volume, and the serum creatinine above the • Should be corrected for body surface area • Creatinine Clearance is a more accurate test • Decreases naturally with age of renal function • Reference Ranges: • Clearance is defined as the mL of plasma – Males >85 mL/min/1.73 m2 cleared of a substance per minute – Females >75 mL/min/1.73 m2

Creatinine Clearance

• Problems in collecting 24-hr urine • The purpose of the anion gap is to • Various calculations used to estimate Creatinine determine the etiology of a metabolic Clearance . • Current is the MDRD equation: • The anion gap is a measurement of – http://www.niddk.nih.gov/health-information/health- communication-programs/nkdep/lab-evaluation/gfr- unmeasured anions. These unmeasured calculators/Pages/gfr-calculators.aspx anions are the conjugate bases of organic – Corrected for African-American race & sex acids. – Normals are reported as "≥60 mL/min/1.73 m2" – Lactate, ketone bodies from DKA, salicylate…

Anion Gap

CASE #1 • Based on the principle of electroneutrality A 72 year-old woman is admitted after being found unwell + - - in her home by family members. She has a decreased • Anion Gap = [Na ] – [Cl ] – [HCO3 ] level of consciousness and cannot give any history, but • Normal range = 12 ± 4 mmol/L her daughter states that the dosage of one of her diabetes was increased 2 weeks ago, and earlier in the – Normal range varies with methodology. week she seemed to be suffering from a “stomach flu.” On examination, she is hypotensive, tachycardic, and tachypneic. She responds only to painful stimuli but has no other remarkable findings. You order basic laboratory studies and find a [high] anion gap .

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MUDPILES Anion Gap Toxin Organic acid that accumulates High Anion Gap Metabolic Normal Anion Gap (Unmeasured anion) Acidosis Metabolic Acidosis Formic acid (metformin) (most common) Uremic toxins (diabetic, alcoholic, starvation) Acetoacetate, End-stage renal failure β-hydroxybutyrate Methanol intoxication Paraldehyde Ethylene glycol intoxication or from iron toxicity Salicylate intoxication Ethylene glycol Oxalic acid (binds ) Lactic acidosis Lactic acid Salicylates () Salicylic acid

CASE STUDY 2 HYPERKALEMIA

• Na 129, Cl 78, tCO2 12 • Is the sample hemolyzed? • Anion Gap = 129 – (78 + 12) = 39 – Hemolysis raises potassium • Blood = 1,890 mg/dL • How old is the sample? • Diagnosis is diabetic ketoacidosis

HEMOGLOBIN A CALCIUM 1c Glycosylated Hemoglobin Chemical form Percentage Free (ionized) 47% • Glucose reacts non-enzymatically with -bound (mostly ) 43% hemoglobin to form HbA Complexed (, carbonate, citrate, etc.) 10% 1c • The extent of glycosylation increases with pH incr.-> increasing glucose concentration Ca2+ + albumin-H Ca-albumin complex + H+ <-pH decr. • The HbA1c level is an indication of the • If the albumin is significantly decreased (malnutrition, average glucose level for the past 3 months liver disease), the total calcium will be low but the • Reference Range: 4-6% ionized calcium may be normal.

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HEMOGLOBIN A1c Point-of-care Glucose Tests

Usage Cutoff • Fasting whole blood glucose is 12-15% lower than Goal for diabetic control <7.0% plasma. Screening for diabetes >6.5% • Fasting capillary glucose is 2-5 mg/dL higher than venous. • But post-prandial capillary glucose averages 30 mg/dL higher than venous. • Capillary glucose may be depressed with poor perfusion: cold, hypotension or shock, Raynaud’s, vasopressors, dehydration.

Liver Function Tests • Enzymes released from liver cells when injured – (AST) – (ALT) – – Gamma-glutamyl transferase (GGT) • , total and direct • Why are there so many LFTs?

Classifying acute liver disease Carcinoma of Pancreas Acute hepatocellular necrosis Obstructive jaundice • Viral hepatitis • Gallstone Bile duct obstruction • Alcoholic hepatitis • Stricture • Wilson’s disease • 15 • α-1 Anti-trypsin deficiency • Abscess 10 • Autoimmune hepatitis • Tumor or metastasis

• Hemochromatosis • Drug-induced 5 • Infectious mononucleosis • Primary biliary ULN Times • Non-alcoholic fatty liver • Primary sclerosing 0 disease cholangitis AST ALT ALP GGT

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Acute Hepatitis B Non-hepatic cause of jaundice

Surgery resident with jaundice • Dispatched for an 11-year old male who is “not acting right” and has been . 120 • Arrived to find AA patient lying in bed, 100 80 eyes open and staring ahead but otherwise 60 unresponsive. 40 Time ULN 20 0 AST ALT ALP GGT

Non-hepatic causes of jaundice Non-hepatic causes of jaundice

• Mother states patient developed a headache • Despite dark complexion, patient appears 2 days ago and has been vomiting since jaundiced, especially on palms. yesterday night. • Skin warm, not excessively dry • Denies diarrhea, negative PMH • RR 24, HR 135, BP 100/60, SpO2 100% • Treating with Aleve and Pedialyte but no • Glucose 150 mg/dL aspirin. • ECG sinus rhythm • Mother Haitian, father African-American • Abdomen soft & non-tender, not distended

Non-hepatic causes of jaundice Diagnosis

• Hemolytic anemia • Autoimmune hemolytic anemia – Transfusion-related – Incidence 1:80,000 in children – Autoimmune – Many cases are idiopathic – DIC, hemolytic uremic syndrome – Some cases may be triggered by: – Hemoglobinopathies, e.g., sickle cell anemia • Drugs, e.g., penicillin, α-methyldopa – Glucose-6-phosphate dehydrogenase deficiency • Viral illness

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Laboratory Studies Laboratory Studies

• CBC • Chemistry tests – Hemoglobin = 2.4 g/dL – Bilirubin – MCV normal (normocytic) • Total bilirubin increased – MCHC normal (normochromic) • Indirect bilirubin increased, more than direct – Ammonia normal • Reticulocyte count increased • Enzyme tests • Direct anti-globulin (Coombs test) positive – AST & LDH increased – Sign that RBCs are coated with antibodies – Alkaline phosphatase & GGT WNL

Laboratory Studies Bilirubin Metabolism

• Urine tests – Urine bilirubin (bile) negative or weak pos. – Urine urobilinogen increased

Diagnosing Acid-Base Disorders • Look at the pH first Acid-Base and Blood Gases – If pH<7.35  Acidosis – If pH>7.45 

• Look at the CO2 and next to determine the primary cause. • Once you have determined the primary cause, determine if there is compensation by the other component.

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ACIDOSIS ALKALOSIS

ACIDOSIS ALKALOSIS

EXAMPLE 1 EXAMPLE 2

• pH 7.28, pCO2 58, bicarbonate 33 • pH 7.28, pCO2 23, bicarbonate 10.8 • Diagnosis: Partially compensated • Blood glucose 1,890 mg/dL • Diagnosis: Partially compensated Metabolic • Note that we determined the primary Acidosis disorder is respiratory first, then we looked – DKA at the bicarbonate second to see if there was • Tip for ventilator management: The low carbon compensation. dioxide here is compensatory and should not be fixed.

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What’s new with Troponin?

• Original (conventional) troponin assays CARDIAC BIOMARKERS lacked sensitivity – Most normal patients were “Not detected” – Needed to monitor Tn levels for 6-9 hr until MI ruled out • Newer (high-sensitivity) troponin assays are more sensitive

Troponin I Non –MI causes of elevated troponin

• iSTAT cTnI at Chippenham • Defibrillation • Cardiac surgery • High sensitivity TnI with cutoff 0.8 ng/mL • Myocarditis • Renal failure • Order every two hours: 0 & 2 hr. • Myocardial contusion • Pulmonary embolism • Normal TnIs without upward trend at 2 hr • Acute and chronic • Sepsis, Shock rules out AMI congestive heart • Hypothyroidism failure

Third Universal Definition of MI Ultra-sensitive Troponin Assays • Detection of a rise and/or fall of cardiac biomarker values [preferably cardiac troponin (cTn)] with at • Will be able to measure troponin levels least one value above the 99th percentile upper within the normal range. reference limit (URL) and with at least one of the • Will be able to follow patients as they following: progress through the normal range to – Symptoms of ischemia. – New or presumed new significant ST-segment–T wave abnormal. (ST–T) changes or new left bundle branch block • May permit ruling out MI in one hour. (LBBB). – Development of pathological Q waves in the ECG.

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B-Natreuretic Peptide (BNP)

• A test for CHF • BNP is released by the left ventricle when it TOXICOLOGY TESTS is stretched • False-positives in pulmonary HTN, pulmonary embolus

Drugs Not Detected on Routine Acetaminophen overdose Urine Drug Screens • “Bath Salts” • Jimson weed – Synthetic cathinones • Salvia • Ecstasy (XTC, • Rohypnol (flunitrazepam) MDMA, Molly) • Gamma- • Metcathinone (Cat) hydroxybutyrate • 25I-NBMD (25I) (GHB) • LSD • K-2 or Spice • Fentanyl – Synthetic cannabinoids

CSF TESTS

• Normal color and clarity of CSF are colorless and clear (like water) TESTS – Xanthochromia is a pink, yellow or orange color in centrifuged CSF indicative of CNS bleeding, especially subarachnoid hemorrhage. • Most useful if patient presentation is delayed >6h. – Pleocytosis is an increased number of RBC or WBC in CSF which causes a cloudy specimen

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CSF TESTS Bacterial

• Tip: In bacterial meningitis, look for a • Normal CSF glucose is ≈ 2/3 of serum cloudy specimen with elevated WBC, • CSF glucose <1/2 of serum is suggestive of protein and lactate, decreased glucose, and bacterial meningitis presence of bacteria on the Gram stain. • CSF WBC >1,000/µL usually caused by bacterial meningitis

URINALYSIS

Urinalysis Patterns Urinary tract infection • Urinary tract infections – Dysuria, cloudy, odor, RBC (chem & micro), WBC (chem & micro), protein, bacteria (chem [nitrite] & micro) • “Nephritic” urine – Acute glomerulonephritis • RBC, WBC, protein, RBC & WBC casts • – Glucose + ketones • Tip: Berra’s Rule: “You can see a lot by looking.”

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RED BLOOD CELL TESTS: HEMATOLOGY TESTS RBC, Hemoglobin & Hematocrit • CBC • Tip: Generally, the same factors control – RBC and Red Cell Indices RBC, Hct and Hb. – Hemoglobin and Hematocrit • Tip: Remember the average RBC is 5, the – WBC average Hb is 15 and the average Hct is 45. – Differential cell count • Tip: The ratio of Hct to Hb in normal red – Platelet count cells is 3:1. • Coagulation tests • Tip: The transfusion trigger is a Hb < 7. – PT and PTT

Effects of Hemorrhage on RBC Mean Cell Volume (MCV) and H&H • Immediate • Small red cells (“microcytosis”) often due – with normal RBC and H&H to iron-deficiency anemia • Acute – Dietary – Dilution with decreases in RBC and H&H – Chronic (occult) bleeding, e.g., GI hemorrhage • Normocytic • Large red cells (“macrocytosis”) often due – Increased reticulocytes to vitamin B12 or folate deficiency • Chronic – Dietary or pernicious anemia – Decreased RBC and H&H – • Microcytic due to iron deficiency

White Blood Cell Count Differential Cell Count

• Tip: Bacterial infections tend to give • An enumeration of the different types of moderate increases (teens to 20’s). With WBC in the blood very high WBC, think about leukemia. • Consists of neutrophils, lymphocytes, basophils, eosinophils and monocytes • Tip: The absolute cell count (cells/L) is often more useful than the percentage.

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Wright-stained Blood Smear Neutrophils

• Phagocytic cells that ingest bacteria, dead tissue, etc. – Increased in infections and inflammation • Mature neutrophils have segmented nuclei PMN (“segs”) Lymph – Also called polymorphonuclear cells (PMNs, “polys”) • Less mature neutrophils have banded nuclei (“bands”, “stabs”)

Neutrophil maturation Neutrophils

• Tip: In bacterial infections, look for , an elevated WBC and elevated neutrophils. – Look for a increase of less mature neutrophil forms in the blood (the bands, “bandemia”) as the body recruits cells from the marrow to fight the infection. • This is called a “left-shift” for historical reasons.

A case of bacterial infection CBC Results (partial)

• 36 year old female Cell Percentage Normal Range 3 • Infection of chest wall WBC 11,800/μL 4.5-1110 PMN (segmented) 64% 50-70% Bands 21% 0-5% Lymphocytes 5% 20-40% Monocytes 7% 1-6% Eosinophils 3% 1-5% Basophils 0% 0-1%

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International Normalized Ratio Prothrombin Time (PT) (INR) • Tests the extrinsic coagulation pathway • Is the ratio of the patient’s PT to the normal • Increased by DIC, liver disease PT, corrected for the sensitivity of the • Prolonged by warfarin (Comadin®) reagents used to do the test • Difficult to standardize • Provides a universal yardstick to measure the effect of warfarin • Reference ranges are variable • Tip: The target INR for most anti- coagulation is 2-3.

Activated Partial Other markers of coagulation Thromboplastin Time activation • Tests the intrinsic coagulation pathway • D-dimer • Increased by DIC, liver disease, hemophilia – Very sensitive but not specific test for deep A & B vein thrombosis/pulmonary embolism • Prolonged by heparin • Use to rule out, not rule in DVT • Reference ranges often lab-specific • Will be positive wherever there is bleeding & clot – Lab often specifies a therapeutic range for • Fibrin degradation products (FDP, FSP) heparin therapy (1.5-2  normal value) – Positive in disseminated intravascular – Heparin dosing is often weight-based coagulopathy (DIC)

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