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Electrolyte Review

Elizabeth Michalets, PharmD, BCPS, CPP Mission Hospitals Pharmacy Education Coordinator

UNC Community Based Faculty Clinical Associate Professor of Pharmacy

Objectives • Discuss common laboratory tests and

assessments such as electrolytes, glucose, renal function tests, liver function test, complete blood count, and urinalysis

• Review normal and abnormal values and management strategies

• Utilize patient case discussions for application

Lab Values • Electrolytes

Na, K, Mg, Ca, Phos • Serum glucose • Renal function tests • Liver function tests • CBC • Urinalysis

Case #1 • CR is a 50 yo female recently

diagnosed with small cell lung CA. She was admitted to the ER by her family with reports of confusion and lethargy. She is 60 kg, and her skin turgor is normal.She has been on carbamazepine for her seizure disorder. Labs are: Na+ 119 meq/L, K+ 4 meq/L, serum osmolality 230 mOsm/kg, urine osmolality 700 mOsm/kg, urine Na+ 300 meq/L

Case #1: Initial Treatment Options

• (1) Fluid restriction of 500 ml/day • (2) Discharge to home and instruct her

to ask MD about stopping her chemo • (3) Start 3% NaCl IV at 14 ml/hr • (4) Start salt 1 teaspoon po tid

NEJM 2003;342(1):1581-89; NEJM 2003;342(1): 1493-99

Sodium

• Predominant extracellular cation • Reflects total body water • Normal ranges:

serum: 135-145 meq/L urine: 40- 200 meq/L serum osmolality: 280-300 mOsm/kg urine osmolality: 300-900 mOsm/kg

NEJM 2003;342(1):1581-89; Med Clin N Am 1997;81(3):585-603

Hyponatremia • CNS symptoms: headache, lethargy,

decreased reflexes, seizures • Most severe when Na+ < 120 meq/L • Subcategories: (serum Osm)

hypotonic (majority of cases) normotonic (TG > 1500) hypertonic (hyperglycemia, mannitol) Na+ p 1.6 meq/L for each 100 mg/dl n I glucose)

NEJM 2003;342(1):1581-89; Med Clin N Am 1997;81(3):585-603

1. Hypotonic Hyponatremia • Hypervolemic: normal or excess in total

body Na+ but bigger excess in body water • CHF, cirrhosis, edema syndromes,

hypoalbuminia • p serum Osm, n urine Osm, p urine Na+ • Treatment:

fluid and sodium restriction diuretics (loop)

NEJM 2003;342(1):1581-89; Med Clin N Am 1997;81(3):585-603

2. Hypotonic Hyponatremia • Euvolemic: excess in total body water and

normal Na+ (RAS intact) • SIADH, water intoxication adrenal insufficiency,

hypothyroidism • p serum Osm, n urine Osm, n urine Na+ • Treatment:

diuresis (loop diuretics) fluid restriction (< 500 ml qd) IV Na+ (if symptoms or Na+ < 120 mEq/L) demeclocycline 300-600 mg po bid (if SIADH with symptoms/Na+ < 125

NEJM 2003;342(21):1581; Med Clin N Am 1997;81(3):585-603

SIADH

• CNS abnormalities (meningitis, head traumas, brain abscess, SAH,hematoma)

• Pulmonary disorders (pneumonia, COPD,tuberculosis, acute respiratory failure)

• Malignancies (small cell lung, pancreas, duodenum, nasopharynx, leukemias, Hodgkin’s lymphoma

• Spinal cord lesions, Guillain-Barre’ Syndrome • Hypothyroidism, glucocorticoid insufficiency

• Drugs!!

Applied Therapeutics 7th Ed 2001

Drugs that Cause SIADH • SSRIs • TCAs • Antipsychotics • Carbamazepine • NSAIAs • Morphine • Bromocriptine • Morphine • Nicotine

• Desmopressin • Oxytocin • Cyclophosphamide • Vincristine • Vinblastine • Chlorpropamide • Tolbutamide • Clofibrate

NEJM 2003;342(1):1581-89; Med Clin N Am 1997;81(3):585-603

3. Hypotonic Hyponatremia • Hypovolemic: extracellular fluid deficit but

greater deficit in Na+ than fluid • Over diuresis, prolonged vomiting or NG

suctioning, burn patients, cerebral salt wasting • Signs: poor skin turgor, oliguria, orthostasis, dry

mucous membranes • p serum Osm, n urine Osm, low urine Na+ • Treatment:

fluid replacement with 0.9% NaCl or LR at 125-200 ml/hr

NEJM 2003;342(21):1581-89; Med Clin N Am 1997;81(3):585-603

Treatment With Na+- Containing Fluids

• IV Na+ needed if symptomatic or Na+ < 120 mEq/L regardless of cause!

• 0.9% NaCl contains 154 mEq/L Na+ • 3% NaCl contain 513 mEq/L Na+ or 256 meq/500 ml bag • Na+ deficit (meq) =

(0.5) (Wt) (Desired Na+ - Measured Na+) • Replace 1/3-1/2 over first 12 hours then rest over next

several days • Risk of rapid correction: irreversible demyelination

(correction > 2 mEq/l/hr or 12 mEq/l/day) • Use central line for 3%

Nephrology PSAP module Figure 4-8;2001

Case #1 Answer • 3 is correct answer - 3% NaCl with 50%

of Na replacement over 1st 24 hours • Patient has serum sodium of 119 meq/L

and is symptomatic • Probable SIADH from carbamazepine

or from lung CA • Transition over to another

anticonvulsant • May need demeclocycline

NEJM 2003;342(20):1493-99; Med Clin N Am 1997;81(3):585-603

Hypernatremia • Water deficit > Na+ deficit • Dehydration or accidental sodium

loading • Few symptoms until Na+ > 160 mEq/L • Intense thirst, muscle weakness,

confusion, coma • Correction rate: 0.5 mEq/l/hr or < 10

mEq/l/day • Rule of thumb: 1/2 over first 12-24

hours and remaining over next 24-48 hrs

NEJM 2003;342(20):1493-99; Med Clin N Am 1997;81(3:585-603

Hypernatremia • Oral route preferred for replacement • Tap water or D5%W, 0.25% NaCl (with

additive) or 0.45%NaCl • Treatment:

Water Deficit (liters) = 0.6(LBW) 1 - ( Normal Na) (Present Na)

Case #2

• AB is a 65 yo female in a nursing home. She has had a GI virus with N&V and has refused all oral intake for 72 hours. She weighs 65 kg, has poor skin turgor, and her serum Na+ is 165 meq/L.


• (1) Diuresis her with lasix 20 mg IV stat to remove sodium

• (2) Start D5W IV at 100 ml/hr • (3) Order up McDonald’s french fries to

satisfy her salt craving • (4) Ask her to drink 4 liters of bottled

water today

Case #2 Answer

• 2 is correct answer • The patient has a free water deficit from

lack of oral intake • Patient may need 4-5 liters of free water

over the next 2-3 days • Only replace 1/3-1/2 over first 12-24

hours

Med NEJM 2002;339(7):451-58; Clin N Am 1997;81(3):611-39

Potassium

• Intracellular cation (2% extracellular) • Normal range: 3.5-5 meq/l • 80% excreted by kidneys • Cellular balance maintained by Na+K+

ATPase pump

Med NEJM 2002;339(7):451-58; Clin N Am 1997;81(3):611-39

Hypokalemia • Common causes: hypomagnesemia, GI

losses (diarrhea, vomiting, fistula), alcoholism , DKA, metabolic alkalosis, Cushing’s syndrome

• Drug Causes: diuretics, fludrocortisone (mineralocorticoid) pseudoephedrine, amphotericin, cisplatin, inhaled B2 agonists, foscarnet, aminoglycosides, high dose penicillins (pencillin, ampicillin, nafcillin),licorice, gossypol

Arch Int Med 2000;160:2429-36;Med NEJM 2002;339(7):451-58; Clin N Am 1997;81(3):611-39

Hypokalemia • S&S: muscle weakness and cramping,

fatigue, confusion, arrhythmias: heart block, QT prolongation, flattened/inverted T waves

• S&S when K+ < 3 mEq/L • Maintain K + > 4 mEq/L:

CHF HTN cardiac arrhythmias


Hypokalemia: Treatment Pearls

• Always check for concomitant magnesium deficiency! • If K+ > 3 mEq/L, every 10 meq IV/po will n K+ by 0.1

mEq/L • If K+ < 3 mEq/L, every 20 meq IV/po will n K+ by 0.1

mEq/L • Non-emergent replacement: limit IV rate to 10 meq/hr • Emergent replacement: limit IV rate to 20 meq/hr

(need telemetry for > 10 meq/hr) • Only give 1/2 calculated dose to renal patients • Thrombophlebitis prevention: max conc of 80 mEq/L • Re-check K+ level at least every 4 hours during

administration


Hypokalemia: Treatment Pearls

• Oral preps preferred if K+ > 3 mEq/L • Liquid and powder preps more GI upset, ulceration • Sustained release preps preferred (KDur®) unless

need immediate n in K+ • Levels should n in 72 hrs with SR • Bananas: approx 1 meq/inch

NH Potassium/Magnesium Replacement Protocol 11/04

Case #3

• A 43 yo female with metastatic breast CA has undergone therapy with cisplatin. She has also experienced significant diarrhea. Serum lytes: Na+145 meq/L, K+ 2.8 meq/L, Mg++ 1.2 mg/dl, Phos 2.7 mmol/L, Cl- 110 meq/L, HCO3 15 meq/L. Her ECG shows NSR.


• (1) KCL 20 meq/hr IV on telemetry • (2) MSO4 4 grams IV over 4 hours • (3) Instruct her to eat the next case of

bananas unloaded at Ingles • (4) Both #1 and #2

Case #3 Answer

• 4 is correct answer • Magnesium is a necessary co-factor for

cellular uptake of K+ • K+ < 3 meq/l requires 20 meq/hr but on

telemetry; may p to 10 meq/hr once K+ up to 3 meq/L

• Ultimately may need up to 90 meq KCL to n K+ to 3.5 meq/L

Med Clin N Am 1997;81(3):611-37

Hyperkalemia • Causes: p renal function, excessive

intake, extracellular shifts ACE-I/ARB Acidosis TMP/SMX Cyclosporin Hyperglycemia Hemolysis Adrenal insufficiency Tissue trauma (catabolism)

• S&S: muscle weakness, parathesias, N&V, confusion, arrhythmias: asystole, spiked T waves,

Med Clin N Am 1997;81(3):611-37

Hyperkalemia

• Can see initial ECG changes when K+ > 5 but high risk when > 7

• Treatment Pearls: -treat/prevent cardiac side effects if > 7 regardless of symptoms -treatments can be temporary or permanent

Med Clin N Am 1997;81(3):611-37

Hyperkalemia: Permanent Treatments

• Dialysis • Diuresis if SCr < 3 mg/dl (loops) • Sodium polystyrene sulfonate/Kayexalate®

-binds K+ through resin exchange -may cause Na+ overload -po/NG most effective/in GI tract longer -peak effects 4-6 hours! -retention enema (120-180 ml for 1-2 hrs) works faster (30-90 min) -40 gm p K+ by 1 mEq/L -typical dose: 15-30 gm po X 1then 10 gm po qid until K < 5.5

Med Clin N Am 1997;81(3):611-37

Hyperkalemia: Temporary Treatments

• Calcium chloride or gluconate IV does NOT change K+ abolishes arrhythmias

• Inhaled/nebulized B2 agonists shifts K+ intracellulary

• Sodium bicarbonate IV shifts K+ intracellulary

• Regular Insulin IV with dextrose 50% shifts K+ intracellulary

Pharmacotherapy 4th Ed

The ACCP Report 1993:6; J Em Med 1992;10:735-45

Magnesium

• 90% intracellular • Catalyst for ATPas pump,

neuromuscular function of Ca++ ion • Renally excreted • Normal range 1.8-2.4 mg/dl


Hypomagnesemia

• Causes: chronic diarrhea, malnutrition, alcoholism, malabsorption syndromes, drugs: diuretics, cisplatin, amphotericin, cyclosporin, aminoglycosides

• S&S: weakness, tremors, arrhythmias, seizures

• Symptomatic if Mg++ < 1 mg/dl


Hypomagnesemia

• Renal excretion occurs when a threshold is met by acute ns in serum concentrations

• Treatment Pearls -bolus injections not helpful for restoring body deficits -50% of IV dose is excreted in urine -po replacement unless Mg++ < 1 or symptomatic -1 gm IV MgSO4 = 8 meq Mg++ - Max infusion 1.5 ml/min for 10% soln - Monitor for hypotension & bradycardia with IV dosing


Hypomagnesemia

• Mg++ < 1 mEq/L or Mg++ 1-1.4 mEq/L and symptomatic asymptomatic 2 meq/kg deficit 1 meq/kg deficit 6gm/1000 over 3 hours then MOM 5 ml qid 10gm over next 21 hrs then (33 meq/5 ml) 6gm daily for 4 days Maalox/Mylanta 15ml tid (16.7 meq/5ml) MgOxide 400mg qid (20 meq/tab)

• Diarrhea is dose limiting factor

MH Potassium/Magnesium Replacement Protocol 11/04


Hypermagnesemia

• S&S not present until Mg++ > 4 • S&S: QT prolongation, bradycardia, heart block, N&V • Most common cause: Clcr < 30 ml/min • Treatment only for symptomatic pts with Mg++ > 5 or all

pts with Mg++ > 8 • Treatment:

Ca++ 5-10 meq IV over 5-10 min Diuresis Dialysis

Pharmacotherapy 5th Ed;2002

Calcium • Abnormalities often seen in oncology patients • Normal range 8.5-10.5 mg/dl • Regulated via Vit D, parathyroid hormone, calcitonin • 40% bound to albumin and only 47% is free (ionized) and

is physiologically active • Changes in albumin effects free Ca++ • Corrected Ca = Observed Ca + 0.8 (Normal albumin - Obs albumin)

• True hypocalcemia may occur after massive blood transfusion due to citrate anticoagulant in blood

• 100-300 mg Ca over 5-10 min (1 gm CaCl or 2-3gm CaGluconate)

Case #4

• A 25 yo male with DKA has the following labs: Na+ 133 meq/L, K+ 3.6 meq/L, Mg++ 1.8 mg/dl, Phos 0.7 mg/dl, Glucose 500 mg/dl. He is on IV fluids and an insulin drip. He weighs 75 kg.


• (1) Call Biltmore Dairy for 3 tubs of ice cream but pray that he doesn’t get milk alkali syndrome

• (2) 3% NaCl at 25 ml/hr • (3) KPhos 39 mmol IV over 8 hours • (4) Observe the patient for respiratory

failure

Crit Care Med 1985;13(1):16-18; Clin Pharm 1988;7:123-28

Phosphorus • Intracellular • Essential for ATP formation, RBC

function (2,3-DPG), cell lipid membranes, metabolism

• Renally excreted with complex homeostasis with Vit K, parathyroid hormone, Ca++

• Normal range: 2.5-5 mg/dl


Hypophosphatemia

• Causes: DKA, alcoholism, refeeding syndrome, antacids, hyperparathryoidism

• Drug causes: phos binders, sucralfate, glucocorticoids

• S&S: muscle weakness (diaphragm included), parathesias, seizures, p cardiac contractility

• S&S most prevalent with phos < 1 mg/dl


Hypophosphatemia • > 2 mg/dl 1-2 mg/dl < 1 mg/dl

mild mod severe 0.075-0.1 mmol/kg 0.2-0.3 mmol/kg 0.5-0.6 mmol/kg 50-150ml 150-500ml 125-1000ml 2-4 hours 4-8 hours 8-12 hours

• Central line: 9 mmol/50 ml max D5W or NS • Peripheral line: 9 mmol/150 ml max D5W or NS • Infusion time: 3 mmol over 30 min max • Rapid infusion causes precipitation with Ca++ and

cardiovascular collapse • Consider using D5W for NaPhos infusions to avoid

hypernatremia


Hypophosphatemia • Oral replacement preferred for Phos > 2 mg/dl • Milk has 7 mmol/cup! • Recheck phos level in am with oral replacement • Product Phos K+ Na+

Kphos IV 3mmol/ml 4.4meq/ml 0 NaPhos IV 3 mmol/ml 0 4 meq/ml Neutraphos 8mmol/cap 7 meq 7 meq (caps/packets) Neutraphos K+8 mmol 14 meq 0

• Dissolve packets in 4 oz of water


Hypophosphatemia • Other Treatment Pearls:

- Reduce dose by 25% if corrected Ca++ is high (> 10.4 mg/dl) - Recheck phos level 3-4 hours after conclusion of infusion with IV -Recheck phos level next am with oral dosing -Monitor K+, Mg++, Ca++ since they may also be deficient with p phos

Case #4 Answer

• 3 is correct answer (KPhos IV) • Patient will need 0.5-0.6 mmol/kg of

Phos • 39 mmol KPhos = 57 meq K+ • Na+ does not need to be corrected

since glucose is elevated = corrects to 139


Hyperphosphatemia • Phosphorus is not dialyzed so ESRD pts usually

develop • Other causes: hypoparathyroidism, bone metastasis,

bone fractures, tumor • S&S: tetany, arrhythmias, seizures • Concern: precipitation with Ca++ in lungs, kidneys,

cornea, blood vessels • Ca/Phos product an indicator of risk: > 60 but p

solubility in alkaline environment


Hyperphosphatemia • Treatment Pearls

-Phosphate binders hasten excretion -Al-containing product most effective but risk of Al toxicity -Al toxicity after 1 month of continuous use (encephalopathy, bone disease) -Use Al product (1-3 gm/day) 5-15 ml tid until Ca/Phos product < 70 and Phos < 5 then switch -Ca++ product 4-6 gm/day (2-3 tabs with meals) -Other option: Renagel/Sevelamer� 800-1600 mg tidcc and titrated to phos level ($3/day vs $0.90/day) polymeric binder -Max response in 2-4 days

Case #5

• PT is a 65 yo female who presents to your pharmacy. She asks for your recommendation on her labs: BP 120/70, HR 65, fasting glucose 110 mg/dl, LDL 95 mg/dl, HDL 50 mg/dl. She is 5’5”, weighs 90 kg and has a positive family history for early MI (father at age 59).


• (1) Instruct her to throw a party for her friends to celebrate her superb health

• (2) Recommend starting simvastatin 40 mg po qd

• (3) Explain to her what “prediabetes” is and recommend some lifestyle modification (weight loss, exercise) along with an annual fasting glucose

• (4) Both #2 and #3

Diabetes Care: 2004;27:S3

Serum Glucose • Normal range in many labs: 70-105 mg/dl • Desired fasting (8 hrs) blood glucose:

< 100 mg/dl • Desired 2 hour post OGT (75 gm):

< 140 mg/dl • “Prediabetes:”

fasting 100-125 mg/dl or 2 hour post OGT 140-199 mg/dl

• Prediabetes: life style modification and yearly screening

Diabetes Care: 2004;27:S3; NEJM 2001;345(19):1359-67

Serum Glucose

• ICU patients: desired 80-110 mg/dl • Hypoglycemia: < 60 mg/dl (cognitive

changes when < 50 mg/dl) • Desired Hb A1C < 7%

(average over last 2-3 mo)

Case #5 Answer

• 3 is correct answer • Need to address prediabetes • Pt’s lipids are at goal so statin not

needed

Case #6

• ED is a 75 yo male with DM and CHF. He was started 2 days ago on captopril 50 mg po tid and lasix 40 mg po qd. On presentation he has the following labs: BP 125/80, HR 68, Na+ 140 meq/L, K+ 5 meq/L, BUN 40 mg/dl and SCr 2 mg/dl. He is 5’10” and weighs 75 kg.


• (1) Commend him on his high serum creatinine since it reflects lots of recent exercise with weight lifting

• (2) Stop the captopril since he may be in acute renal failure from starting too high of an initial dose with lasix

• (3) His estimated Clcr is approx 60 ml/min

• (4) Both #2 and #3

Applied Therapeutics 7th Ed; 2001

Renal Function Tests • Creatine o comes from skeletal muscle

breakdown o converted in liver to creatinine o eliminated by kidney

• Creatinine used as an assessment of renal function since it is: filtered at glomerulus not reabsorbed or secreted not metabolized by kidney

• Normal range for creatinine conc in serum: 0.7-1.3 mg/dl

•

Critical Care Clin Companion 2000; Applied Therapeutics 7th Ed; 2001

Renal Function Tests • Limitations in estimating creatinine

clearance (Clcr): -serum creatinine must be stable -patients with little muscle mass -patients with liver disease -pediatrics (< 18 yrs)

• Cockcroft and Gault Method most validated: (140-age) (lean body weight) X 0.85females ( SCr) (72)

• Serum creatinine not rounded to 1 at MH

Crit Care Clin Companion 2000; Applied Therapeutics 7th Ed; 2001

Renal Function Tests

• Gold standard measurement is: Clcr based on 24 hour urine collection

• Clcr (ml/min) = (vol urine in 24 hrs)(urine Cr conc) (SCr) (1440)

• Must ensure that all urine is collected for 24 hrs since diurnal variation in Cr excretion


Renal Function Tests • Definition of acute renal failure:

-n Scr of > 0.5 mg/dl from baseline if Scr < 2 mg/dl -n Scr of > 1 mg/dl from baseline if Scr > 2 mg/dl -50% p in Clcr

• Non-renal causes of n SCr: cimetidine trimethoprim rhabdomyolysis lab interference (ketones, cefoxitin)


Renal Function Tests • Blood urea nitrogen (BUN) also

considered measure to be renal function test

• Normal range: 6-20 mg/dl • End product of protein metabolism and

filtered by kidneys • Good screen for renal dysfunction but

not to quantify degree of dysfunction • Other influences on BUN:

protein intake liver disease GI bleeding hydration (depletion or CHF)


Renal Function Tests

• BUN/Cr ratio used to eval hydration status

• Normal ratios is 10-15 • Ratio > 20 suggests dehydration

(prerenal azotemia) but also seen with GI bleeding

• Ratio < 5 may be disorder with synthesis ie hepatitis

Case #6 Answer • 2 is correct answer - pt may be in acute

renal failure • Need a baseline SCr to completely

assess • His estimated Clcr is 33 ml/min but

probably worse • Clcr estimate not accurate in the setting

of acute renal failure

Pharmacotherapy 5th Ed:673

Pharmcotherapy 5th Ed 2002; Emergency Med 2000;43-45

Liver Function Tests

• Transaminases (ALT, AST) intracellular enzymes found inside hepatocytes

• ALT: 8-51 u/L AST: 11-41 u/L • ALT found in cytoplasm vs AST found in

mitochrondria and in any tissue with high metabolic rate:cardiac, skeletal muscle

• ALT more specific for hepatocyte • Elevations suggest leakage from damaged (not dead)

cells • Both n during acute hepatocellular damage



• 20X n with acute hepatitis, drug induced hepatocellular damage, mononucleosis, ischemia

• 4-5X n with alcoholic liver disease, chronic hepatitis, liver metastasis

• AST also increased after MI, skeletal muscle trauma, CPR


Liver Function Tests • Alkaline Phosphatase 5-28 u/L • Found in liver and bone • Formed by hepatic cells and secreted into bile • ned when the flow of bile is interrupted/bile

obstruction • Causes of n:

intrahepatic (3X n) - CA, abscess extrahepatic (> 5X n) - bile duct stones, drug-induced cholestatic jaundice, pancreatic CA


Liver Function Tests • GGT 0-65 u/L males and 0-39 u/L females • More sensitive to liver disease than Alk Phos since

it’s not found in bone • Indicative of obstructive jaundice • Good indicator of recent alcohol ingestion since it ns

in response to enzyme induction from alcohol and drugs

• May also be ned by inducer drugs: phenytoin, carbamazepine, barbiturates, warfarin


Liver Function Tests • Total bilirubin 0.2-1.2 mg/dl

Direct bilirubin 0 -0.3 mg/dl Indirect bilirubin 0.1 - 0.8 mg/dl

• Break down product of hemoglobin • Highly bound to albumin • Hepatic parenchymal cells conjugate bilirubin to

glucuronide form (conjugated or direct) • Conjugated form excreted in urine, feces, bile • Unconjugated form water insoluble • Bile flow obstruction/cholestatis: both arened • Hepatocellular damage: can’t conjugate so total and

indirect are ned



• Albumin 3.5-5 g/dl • Produced by liver but changes are not specific to liver • Also ped in malnutrition, ascites, sepsis, hemorrhage • Half-life is 20 days so not an acute index

• Clotting factors: I, II, V, VII, IX and X made in liver • PT/INR elevated in severe, chronic liver disease • < 20% normal clotting factors before n • May not respond to Vit K

Pharmacotherapy 5th Ed:675

Emergency Medicine Oct 2000

Some Medications that n LFTs

• Hepatocellular necrosis: isoniazid, phenytoin, APAP, iron, amiodarone, some NSAIAs, methyldopa

• Steatosis: steroids, valproic acid, TPN

• Cholestasis: chlorpromazine, rifampin, erythromycin estolate, estrogens

Case #7

• TL is a 50 yo female who presents with a 2 day history of “dark urine,” and malaise. She reports only occasional alcohol use and premarin as her only medications. Her labs are: ALT 50 u/L, AST 40 u/L, GGT 125 u/L, Alk Phos 60 u/L, total bilirubin 6 mg/dl, albumin 4 g/dl, INR 1


• (1) Her LFTs indicate cholestatic jaundice

• (2) Her LFTs indicate hepatocellular damage

• (3) Tell her to see a MD for possible seasonal depression which is causing her malaise

• (4) LFTs are meaningless lab tests that should never be ordered

Case #7 Answer • 1 is correct answer - cholestatic LFTs • n T bili, alk phos, GGT indicate

obstructive pattern of bilirubin • ALT, AST normal and reflect

hepatocellular enzymes • Estrogens reported to cause cholestasis

with jaundice • Most likely in 1st 6 months in older

women vs OC use in young women

Applied Therapeutics 7th Ed 2001; Mission Hospitals Laboratory 2004

Hematology: complete blood count

• White blood cells (WBC) 3.2-11.8 x103/mcL Absolute neut (ANC) 1.3-8.1 x103/mcL Hemoglobin (Hb) m 12.9-18.1 g/dl f 11.5-16.5 g/dl Hematocrit (Hct) m 39.2-54% f 36.6-50.2% Red Blood cells (RBC) m 4.1-5.9 x 103/mcL

f 3.7-5.56 x103/mc

Platelets (PLT) 132-400 x103 • *females lower than males due to menses and p

androgren


Hematology: complete blood count

• Mean cell vol (MCV) 80.5-101 fl Mean cell hem (MCH) 27.2-34.6 fl Mean cell hem conc 31-37% (MCHC) RDW 10.5-15.5%


Heme: WBC differential

• % of of total WBC cell:

neutrophils 39.9-75.9 lymphocytes 14.5-47.3 monocytes 3.7-11.9 eosinophils 0-6.2 basophils 0-1.8 bands 0-5 smear


Heme: RBC Indices

• Produced in bone marrow and circulate for 120 days after released

• Transport oxygen • Used to detect anemia • Hb: oxygen carrying compound in RBCs • Hb: depends on number of RBC and

amount of Hb in each cell • Hb: preferable over RBC/reflects

oxygen transport capability


Hematology: RBC Indices

• Hct: roughly 3X Hb • Hct: compares % of centrifuged RBCs

to the separated plasma volume • Hb/Hct p:bleeding, bone marrow

suppression, chronic disease, hemolysis, genetic alteration (sickle cell)

• n HCT: hemoconcentration, polycythemia vera or from chronic hypoxia


Hematology: RBC Indices • MCV: describes average size of RBCs • n MCV: “macrocytosis” Vit B12 or folate

deficiency, alcoholism, chronic liver disease, anorexia, hypothyroidism

• p MCV: “microcytosis” iron deficiency anemia • MCHC (Hb conc) more reliable index than

MCH (Hb weight) • MCV (size) and MCH (weight) change in a

corresponding fashion • MCHC and MCH p in iron deficiency anemia

and MCH n in B12 or folate deficiency

Applied Therapeutics 7th Ed

Special RBC Indices • Reticulocyte % (0.1-2.4% of RBC)

-% of young, immature RBCs - n 3-5 days after stimulus event (bleeding, hemolysis, bone marrow stimulation)

• Erythrocyte sedimentation rate (ESR) -0-20 males and 0-30 females -rate that RBCs settle to test tube bottom -rapid settling with aggregation -very nonspecific -marked n indicates a disease state (RA, neoplasms, SLE, collagen dx, nephritis, pregnancy, infection)


Hematology: WBCs

• No function in vascular system • Transport mechanism to tissues • Formed in bone marrow and released

into circulation for 1 day then migrate to body tissues

• Live 2-3 days outside of the circulation


Hematology: WBCs • Neutrophils abundant (polys, PMNs, segs,

granulocytes) • Phagocytic cells ingest and digest bacteria

fungi and dead cells • n in infection, corticosteroids RA, IBD,

asthma, MI, DKA, physiologic response to stress (trauma, childbirth, exercise)

• n in immature neutrophils (bands) called bandemia, indicates acute infection

• Absolute neutrophil count (ANC): neutrophils + bands


Hematology: WBCs

• Neutropenia: ANC < 2000/mm3

• Agranulocytosis: severe neutropenia • Risk of infection when ANC < 1000/mm3 and

significant when ANC < 500/mm3

• Causes of neutropenia: chemotherapy, lymphomas, metastatic CA

• Lymphocytes: mainly in spleen, lymph nodes • T lymphocytes (thymus gland) or B

lymphocytes (bone marrow)


Hematology: WBCs • n viral infections: mono, mumps, rubella • p HIV, autoimmune diseases • Eosinophils: surface receptors that bind IgG

and IgE • Phagocytic, mast cell secretion, protection

against parasites • n parasitic infections, allergic reactions to

drugs, allergic disorders (hay fever, asthma, eczema), collagen vascular dx, malignancies

• NAACP

Case #8 • JD is a 45 yo male with history of

alcoholism who presents with a 2 day history of fever (102º F) and productive cough. He has also had some hemoptysis for the last 24 hours. Labs: : WBC 15 x103/mcL Bands 10% Hb 9 g/dl and HCT 27% PLT 80 x 103 RBC 3 x 103/mcL MCV 105 fl

Case #9: Initial Assessment

• (1) He has anemia from acute blood loss/possible esophageal varices

• (2) He has macrocytic anemia and needs B12 and folate levels checked

• (3) He has mild thrombocytopenia from probable alcohol ingestion

• (4) He has an elevated WBC count with a left shift due to possible infection

• (5) #1 and #2 and #3 and #4

Case #8 Answer • Correct answer is #5 (all!) • Pt has p Hb, HCT and RBC probably

from acute blood loss (esophageal varices common in alcoholics)

• Pt has n MCV possibly due to B12 and/or folate deficiency (common in alcoholics)

• Pt has p PLT probably due to bone marrow suppressive effects of ethanol

• Pt has n WBC with n bands probably from acute infection (aspiration?)

Pharmacotherapy 5th Ed 2002

Platelets • Thrombocytopenia: < 100/mm3 • Drug Causes:

(1) hapten-immune destruction - (heparin, sulfa antibiotics) -7 days into therapy with large doses - recovery short after drug DC (2) suppression of production in bone marrow -chemotherapy

MH Laboratory Standards; Pharmacotherapy 5th Ed; 2002

Platelets • (3) innocent bystander immune

-quinidine • Medical causes of thrombocytopenia:

sepsis, infections, leukemias, massive blood loss

• Platelet transfusion: PLT < 20 x 103 in nononcology and < 10 x 103 in oncology

Case #9 • AB is an 18 yo female who presents

with complaints of dysuria. She does report being sexually active. Her UA demonstrates: pH 7

• WBC 15/hpf • RBC 0/hpf • Nitrites (-) • Glucose 10 mg/dl • Protein 50 mg/dl • Ketones 0 mg/dl

Case #9: Initial Treatment • (1) She needs to be worked up for

diabetes Type 1 due to the n protein • (2) Her UA strongly indicates a STD

(probably Chlamydia) • (3) She probably has a UTI due to the

presence of pyuria • (4) Suggest that she get worked up for

a psych disorder since her UA is normal, and she may be imagining the dysuria

MH Laboratory Department 2004

Urinalysis (UA)

• pH 4.5-9 • WBC 0-3/hpf • RBC 0-3/hpf • Nitrites (-) • Glucose 0-75 mg/dl • Protein 0-15 mg/dl • Ketones 0-5 mg/dl

Urinalysis in UTI • UA used as a screening test for UTI • Urine culture may need to follow • Pyuria: > 8 WBC/mm3 unspun urine or

2-3 WBC/mm3 centrifuged urine (hpf) • Should be midstream collection! 20-30

ml discarded! • Dipstick leukocyte esterase: detects

esterase activity of leukocytes • Some false (+) and (-) • Pyuria in symptomatic pt correlates well

with significant bacteriuria CID 1999;29:745-58

CID 1999;29:745-58

Urinalysis in UTI • Rapid dipstick: presence of nitrites suggests

bacteriuria since they reduce nitrates to nitrites

• Need 105 bacteria for (+) nitrite • Bacteriuria (uncentrifuged):

> 105 CFU in symptomatic female > 103 CFU in symptomatic male > 102 CFU in catherized pt any growth in symptomatic suprapubic cath

• Can detect smaller numbers if centrifuged • Presence of casts strongly suggests acute

pyelonephritis

Diabetes Care 2004;27:S3

Urinalysis in DM • Monitoring for microalbuminuria

recommended q year in DM after 5 years or after puberty

• Microalbuminuria: urinary albumin > 30-300 mg/24 hours

• Same result for albumin/Cr ratio • Risk of nephropathy: (+) on 2/3 urine

samples during 6 months • Elevations in UA protein nonspecific!

Case #9 Answer • Correct answer #3 - probable UTI • May treat without urine culture on

outpatient basis if not recurrent • Symptoms + pyuria correlate well with

bacteriuria and UTI • Proteinuria nonspecific in UTI and other

situations of stress, inflammation • Nitrite (-) does not r/o UTI • STDs should be diagnosed on vaginal

swab or exam

Asheville, North Carolina

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