Lecture 5 - Fall 2024: Interpretation of Laboratory Assays PDF

9/23/24 Interpretation of Laboratory Assays LECTURE 5 – FALL 2024 1 1 Laboratory Data v What is the purpose for laboratory assays? o Esti...

9/23/24 Interpretation of Laboratory Assays LECTURE 5 – FALL 2024 1 1 Laboratory Data v What is the purpose for laboratory assays? o Estimate nutrient availability in biologic fluids and tissues o Identify clinical and subclinical nutrient deficiencies o Low nutrient concentration causes § Inadequate dietary intake § Increased nutrient needs § Inadequate absorption § Abnormal utilization § Increased excretion o Not always assessment of nutritional status (unless measuring a specific nutrient), rather provides physiologic and metabolic information, which may be related or relevant to nutritional status o Monitor patient’s response to nutritional intervention o Support subjective judgment and clinical assessment findings 2 2 1  9/23/24 Laboratory Data Interpretation v Considerations o No single lab test can diagnose; need to use support data § Physical findings § Anthropometrics § Reported symptoms § Diet analysis § Additional lab values o Direction and trends o Improvement in lab data may not confer clinical benefit o Treat the patient and not the lab value § Results not consistent with the clinical picture should be repeated o Blood levels can be controlled by homeostatic mechanisms and may not reflect storage; Ideally – test should evaluate tissue stores or nutrient function when looking for deficiency § Example: Serum Calcium 3 3 Specimen Types v Whole blood v Serum v Plasma v Blood spots v Urine v Feces v Less common: saliva, sweat, hair, nails v Other tissues: scraping, biopsy samples 4 2  9/23/24 Blood v Total volume of blood is approximately 5-6 liter (8% body weight) v PH of the blood: 7.36-7.44 v Plasma vs Serum o Plasma: Transparent liquid component of blood; water, blood proteins, inorganic electrolytes, clotting factors o Serum: Watery portion of the blood that remains after removal of the cells and clot-forming material 5 5 Chemistry Panels v Basic Metabolic Panel (BMP) o Blood glucose, electrolyte and fluid balance, renal function o Glucose, Ca, Na, K, Cl, HCO3, BUN, Cr v Comprehensive Metabolic Panel (CMP) o Basic Metabolic Panel + 6 additional tests o Albumin, Total Protein, ALP, ALT, AST, Bilirubin 6 3  9/23/24 Chemistry Panels v Electrolyte Panel o Helps detect problems in fluid and electrolyte balance o Typically includes Na, K, Cl, Bicarbonate v Lipid Profile o Total cholesterol, HLD, LDL, Triglycerides v Liver Panel (Hepatic Function Panel, Liver Function Tests, LFTs) o ALT, ALP, AST, Bilirubin, Albumin, Total Protein o May also include GGT, LD, PT, AFP, autoimmune antibodies (ie ANA, SMA) v Renal Panel (Kidney Function Panel) o Na, K, Cl, CO2, Phosphorus, Ca, Albumin, BUN, Cr o May also include BUN/Cr ratio, eGFR, anion gap v Thyroid Function o TSH (thyroid-stimulating hormone), T4, T3 7 Complete Blood Count (CBC) v Red blood cell count (erythrocytes, RBC) v Hemoglobin v Hematocrit v MCV, MCH, MCHC v White blood cell count (leukocytes, WBC) v Differential o Neutrophils o Lymphocytes o Monocytes o Eosinophils o Basophils vPlatelets (thrombocytes) 8 4  9/23/24 Additional Common Labs v A1C v INR v PT v Inflammatory Markers o Pre-albumin o C-Reactive Protein v Specific Nutrients o Vitamin D o Vitamin B12 o Folate v Many others 9 Urinalysis v Specific gravity v pH v Protein v Glucose v Ketones v Blood v Bilirubin v Nitrite v Leukocyte esterase v Urine: mixture of water, inorganic salts and organic compounds o Water soluble vitamins/metabolites may be present o Normal excretion – 600-2500 ml/day o Normal pH – 4.6-8; Protein: 2-8mg/dL o Specific gravity (density) – 1.005-1.025 10 5  9/23/24 Sodium o Major cation of extracellular fluid; extracellular sodium concentrations (135mEq/L) much higher than intracellular levels (10mEq/L) o Regulates extracellular and plasma volume, important in neuromuscular function, maintenance of acid-base balance o Reflects relationship between total body sodium and extracellular fluid volume, and balance between dietary intake of sodium and renal excretory function § 90-95% normal body sodium loss is through urine (rest in feces, sweat) o Indirectly measures hydration status: ↑ dehydration, ↓ overhydration o Normal Range: 135-145 mEq/L 11 11 Sodium o Hyponatremia: o ↓ sodium intake (Na restricted diet) o In most cases: reflects ratio of water to sodium o ↑ fluid intake (excessive water orally, IV without electrolytes) o ↑ losses: diarrhea, vomiting, fistulas, excessive sweating, diuretic administration, Addison’s disease (decreased aldosterone) o ↑ water retention; SIADH (increased anti-diuretic hormone) o ↑ fluid accumulation in body (edema) o disease states: CHF, liver failure, renal failure o false ↓: Na stores intact but water intake is excessive; dilution 12 12 6  9/23/24 Sodium o Hypernatremia o ↑ oral sodium intake –rarely (typically renal excretion compensates) o Reflects change in water status o ↓ inadequate fluid intake (dehydration) o ↑ extra-renal water loss (excessive sweating, open wounds, hyperventilation) o Water loss exceeds sodium loss o Cushing’s syndrome, diabetes insipidus (diluted urine) 13 13 Fluid Assessment v Indicators of dehydration o Dry lips and mouth o Tenting of skin o Fatigue o Irritability o Confusion o Low urinary output o ↓ pulse and blood pressure o Labs § Usually ↑ in sodium § ↑ BUN/Creatinine Ratio 14 14 7  9/23/24 Fluid Assessment v May need fluid restriction with o Edema or ascites o CHF, Renal Failure, Liver Failure – not always o Signs of overhydration § ↓ blood levels of Na, K, albumin, BUN, Cr § ↑ blood pressure § Presence of edema v No single lab value is diagnostic o Labs + clinical exam + hemodynamic evaluation → fluid and electrolyte management 15 15 Potassium o Principle intracellular cation o Involved in maintaining normal water balance, osmotic equilibrium, acid-base balance; regulation of neuromuscular activity (concentrations of K & Na determine membrane potentials in nerves, muscles) o Regulates osmolarity of ECF by exchanging with sodium o Used in the evaluation of acid-base balance and kidney function o Normal Range: 3.6-5 mEq/L 16 16 8  9/23/24 Potassium o Hyperkalemia: o Inadequate excretion of potassium (common in renal failure) o Excessive use of potassium-sparing diuretics (inadequate excretion) o Metabolic acidosis; H+ ions excreted to correct acidosis, K ions retained o Excessive intake; potassium-containing salt substitutes (KCl instead of NaCl) o Excessive IV potassium (IV fluids) o Hypokalemia: o Inadequate dietary intake o Increased losses; diarrhea; vomiting; nasogastric suction o Increased renal excretion o Medications: ie potassium-wasting diuretics, corticosteroids 17 17 Bicarbonate, Total CO2 v Usually ordered along with Na, K, Cl as part of electrolyte panel; or as part of routine CMP (common metabolic panel) v Used to assess acid base balance; helpful in distinguishing between respiratory vs metabolic acidosis or alkalosis v Biochemical marker for the renal system v Normal Value: 21-28 mEq/l 18 18 9  9/23/24 Blood Urea Nitrogen (BUN) v Measures the amount of urea in the blood o Urea is a byproduct of protein metabolism o Formed in liver, excreted by kidneys v Used to assess excretory function of kidneys, metabolic function of liver v Primarily evaluated along with creatinine (Cr) v Normal Value: 5-20 mg/dL v Increased in those with impaired renal function, excessive protein catabolism v Decreased in those with liver failure; also with pregnancy 19 19 Creatinine v Byproduct of metabolism of muscle creatine phosphate to form ATP v Determined by muscle mass v Used to assess excretory kidney function v Normal Values: o 0.6-1.2 mg/dL (males) o 0.5-1.1 mg/dL (females) o Elderly have less muscle mass and lower values v Levels are interpreted in conjunction with BUN v Increased with impaired kidney function, and after surgery or trauma 20 20 10  9/23/24 BUN:Creatinine v Laboratory evaluation of kidney failure v Ratio of BUN:Creatinine is usually between 10:1 to 20:1 v When BUN rises but creatinine does not (increased ratio) o reduced blood flow to kidneys, volume depletion, dehydration, urinary tract obstruction, CHF, gastrointestinal bleeding v When both BUN and creatinine rise o kidney failure 21 21 Calcium v Regulates nerve transmission, muscle contraction, bone metabolism, and blood pressure; necessary for blood clotting v Regulated by the parathyroid hormone (PTH), calcitonin, vitamin D, and phosphorus; complex regulation system: kidney, gastrointestinal tract, bone v Used to evaluate parathyroid function; used to monitor renal failure, hyperparathyroidism, certain cancers, bone metastases v Normal: 8.6-10 mg/dl v Total calcium includes both ionized calcium (50%) and calcium bound to albumin (50%), ionized calcium active form, not affected by protein levels § Correction for low albumin § Corrected Ca = ([4 – serum albumin] x 0.8) + measured calcium 22 22 11  9/23/24 Glucose and Hemoglobin A1C v Glucose o Normal Value: 70-99 mg/dL (adults, fasting) § increased slightly after age 50 o Severe stress from injury or surgery → hyperglycemia v Used to screen for diabetes and monitor diabetic patients o Fasting glucose >125 mg/dL indicates diabetes mellitus o Fasting glucose >100 mg/dL indicator of insulin resistance v Hemoglobin A1C o Normal Value: 4-6% (goal for diabetics 6.5% diagnostic o Measures average glucose concentrations x past 2-3 month 23 23 MCV v MCV: mean corpuscular “cell” volume v There are three main types of corpuscles (blood cells) in your blood o red blood cells, white blood cells, platelets v MCV blood test measures the average size of your red blood cells o Helps distinguish between microcytic and macrocytic anemia o Below normal: microcytic, in presence of iron deficiency o Above normal: macrocytic, in presence of B12 or folate deficiency o Total volume of packed red blood cells (hematocrit) / total # RBC * Hematocrit (Hct) = % of RBCs in total blood volume 24 24 12  9/23/24 MCH & MCHC v MCH: mean corpuscular hemoglobin (27-31 pg/cell) o Hgb / # of RBC o Amount of Hgb in each RBC o Low MCH means low amount of Hgb present per red blood cell o Influenced by size of the RBC, and amount of Hgb in relation to size of RBC o Mirrors MCV (bigger RBC tend of contain more Hgb) v MCHC: mean corpuscular hemoglobin concentration (32-36g/dL, 32-36%) o Measure of Hgb concentration in a given volume of packed RBCs o Helps to distinguish iron-deficiency anemia § Increased: hyperchromia Hemolytic anemia, sickle cell anemia § Decreased: hypochromia (pale color, deficiency of hemoglobin) Iron deficiency § Normal in macrocytic anemia 25 25 Anemia v Anemia: deficiency in size or number of RBCs or amount of hemoglobin they contain (could be blood loss, chronic disease, marrow failure, nutritional, congenital such as sickle cell) v Indices ◦ Hgb/Hct, MCV, MCH, MCHC v Macrocytic Anemia ◦ Folate ◦ B12 Increased MCV, MCH v Microcytic Anemia ◦ Fe Decreased MCV, MCH 26 26 13  9/23/24 Thrombocytes v Platelets (150-350,000/mm3) v Function in the coagulation/clotting of blood, i.e. pathway of fibrinogen to cross-linked fibrin, thrombin is a key intermediary as are other compounds such as the complement proteins ◦ PT/PTT ◦ INR (international normalized ratio) reflects the ratio of a patient’s PT to a laboratory’s control value 27 Alkaline Phosphatase (ALP) v Enzyme found in all tissues; particularly high in bone, liver and bile ducts v Reflects function of liver, and may be used to screen for bone abnormalities v Normal Values: 30-120 units/L v Increased with liver cancer, cirrhosis, hepatitis, bile duct blockage, bone disorders (Paget’s), cancer metastasis to bone; normally ↑ in 3rd trimester of pregnancy, adolescents and children v Decreased with zinc deficiency, hypophosphatasia (rare genetic disorder) 28 28 14  9/23/24 ALT & AST v Alanine Aminotransferase (ALT): Normal Value: 4-36 units/L o Formerly known as serum glutamic pyruvic transaminase (SGPT) o Enzyme found mostly in the liver; also in kidneys, heart, skeletal muscle o Increased with acute or chronic hepatitis, cirrhosis, liver cancer v Aspartate Aminotransferase (AST): Normal Value: 0-35 IU/L o Formerly known as serum glutamic oxaloacetic transaminase (SGOT) o Enzyme found mostly in the heart, liver, and skeletal muscle; but also found in kidneys, brain, pancreas, spleen, and lungs o Amount of AST elevation in blood is related to number of cells injured o Increased with liver damage, MI, acute pancreatitis, severe muscle injury v Both ALT and AST reflect function of the liver o Monitored to assess liver damage, elevated in most liver diseases o Used also in monitoring liver function of those receiving parenteral nutrition 29 29 AST:ALT Ratio v Often compared as a ratio v AST:ALT > 1.0 o Alcoholic cirrhosis o Liver congestion o Metastatic liver tumor v AST:ALT < 1.0 o Acute hepatitis o Viral hepatitis o Infectious mononucleosis 30 30 15  9/23/24 Bilirubin v One of many constituents of bile v Total bilirubin represents o Conjugated bilirubin (Direct) o Unconjugated bilirubin (Indirect) o 70-85% of the total v Normal values o Total: 0.3-1.0 mg/dl o Indirect: 0.2-0.8 mg/dl o Direct: 0.1-0.3 mg/dl v Reflects liver function, also used to evaluate blood disorders, biliary tract blockage v Increased with pancreatic cancer, liver metastasis, gallstones, biliary duct diseases 31 31 Amylase & Lipase v Amylase: o Pancreatic enzyme involved in hydrolysis of starch o Increased with pancreatitis (mainly), cholecystitis, alcohol poisoning o Decreased with advanced cystic fibrosis, hepatitis v Lipase: o Pancreatic enzyme involved in lipid breakdown o Increased with acute pancreatitis, pancreatic duct obstruction o Decreased with cystic fibrosis, permanent damage to pancreas 32 32 16  9/23/24 Arterial Blood Gases v Measures of pulmonary function To be covered in more detail during pulmonary lecture 33 Hepatic Proteins v The acute phase response is a nonspecific physiologic and biochemical reaction to inflammation- in the case of acute injury, infection or neoplasm in particular- leading to marked changes in metabolism v During acute phase response, synthesis of specific plasma proteins are either increased or decreased by at least 25% o Positive Acute Phase Proteins increase o Negative Acute Phase Proteins decrease o Change in these protein is proportional to physiological insult v Indicators of inflammation and reflection of severity of inflammatory response, not indicators of nutritional status o Lab values should be interpreted with caution, better reflection of magnitude of inflammatory response rather an oral protein intake o These indicators (negative acute phase proteins) do not typically respond to feeding interventions in setting of inflammation 34 34 17  9/23/24 Inflammatory Markers 35 35 Albumin v Most abundant plasma protein (55-60% of total serum protein) v Synthesis of albumin takes place exclusively in liver v Major transport protein (hormones, enzymes, medications, minerals, ions, fatty acids, amino acids, metabolites) v Helps maintain plasma colloidal osmotic pressure; when serum albumin levels decrease, water in plasma moves to interstitial compartment (edema) v Decreases in serum albumin: decreased synthesis to spare amino acids for production of positive acute phase proteins, increased degradation rate, change in fluid distribution; most patients experience at least one of these factors o Interpretation in acute care complicated o Changes reflect illness not nutritional status v Plasma levels of albumin decrease with acute inflammation 36 36 18  9/23/24 Transferrin v Transports iron to bone marrow for production of hemoglobin v Plasma transferrin level controlled by size of iron storage pool; when iron stores are depleted, transferrin synthesis increases v Levels ↓ with acute inflammatory reactions, chronic infection/illness, malignancies, liver disease; levels ↑ with pregnancy v Decreased levels reflect inflammation, not useful as measure of protein status v Can be measured directly or estimated (total iron-binding capacity) o TIBC is direct measure of all proteins available to bind mobile iron o % Transferrin saturation = (Serum Fe/TIBC) x 100 37 37 Prealbumin (PAB) & Retinol Binding Protein (RBP) v Prealbumin: transport protein for thyroid hormones o Triiodothyronine and thyroxine (T4) o Combined with Retinol Binding Protein (RBP) transports Vitamin A o Levels decrease with inflammation; not improve with aggressive nutrition support § Levels are often normal with starvation-related malnutrition but decreased in well-nourished individuals with recent stress/trauma o Serum levels also decrease with zinc deficiency, because zinc is required for hepatic synthesis and secretion of prealbumin § Consider zinc status when interpreting low plasma PAB levels v Retinol Binding Protein: transport of retinol (vitamin A metabolite) o Circulates in a complex with prealbumin (PAB) o Can decrease with starvation-related malnutrition but also decreases with inflammatory stress and may not improve with re-feeding 38 38 19  9/23/24 C-Reactive Protein v Positive Acute Phase Reactant v Non-specific marker of inflammation v Exact function of CRP is unclear; increases in initial stages of acute stress (usually within 4-6 hours of surgery or trauma) v Can help estimate and monitor severity of illness v Level can increase as much as 1000-fold o Depending on intensity of stress response v When CRP begins to decrease, patient has entered anabolic period of inflammatory response, beginning of recovery o Once CRP begins to ↓ intensive nutrition therapy may be beneficial 39 39 Inflammatory Markers v Negative acute phase proteins: synthesis ↓ >25% ◦ Albumin ◦ Transferrin ◦ Pre albumin ◦ RBP v Positive acute phase proteins: synthesis ↑ >25% ◦ CRP ◦ Fibrinogen ◦ Prothrombin ◦ others 40 20