Diagnostic Testing Exam 1

Normal Lab Values

Electrolytes

• Sodium: 136-145 mEq/L
• Potassium: 3.5-5.0 mEq/L
• Chloride: 95-105 mEq/L
• Calcium: 8.4-10.2 mg/dL

Carbohydrates

• Glucose: 70-99 mg/dL

Renal Function

• BUN (Blood Urea Nitrogen): 7-18 mg/dL
• Creatinine: 0.6-1.2 mg/dL

Liver Function

• Total protein: 6-7.8 g/dL
• Albumin: 3.5-5.5 g/dL
• Total bilirubin: 0.1-1.0 mg/dL
• Alkaline phosphatase (Alk phos): 20-70 U/L
• AST (Aspartate transaminase): 8-20 U/L
• ALT (Alanine transaminase): 8-20 U/L

Acid-Base Balance

• CO2: 22-28 mEq/L

Immunologic & Serologic Diagnostic Tests

• Acute phase reactants are a group of plasma proteins that increase or decrease in response to inflammatory stimuli, such as acute injury or infection.
• Examples of acute phase reactants include C-reactive protein (CRP), serum amyloid A protein, alpha1-acid glycoprotein, and fibrinogen.
• The acute phase response includes the elevation of these proteins and the decrease in the concentrations of transferrin, albumin, and transthyretin.

C-Reactive Protein (CRP)

• CRP is an acute phase reactant protein that can increase 1000-fold in response to a stimulus.
• The exact role of CRP in inflammation has not been definitively identified.
• CRP may bind to necrotic cell membranes, allowing phagocytes to adhere and activate the complement system.
• Reference range for CRP is 3mg/L, which conveys a high risk for cardiovascular events.
• Values < 1mg/L convey a low risk.

Erythrocyte Sedimentation Rate (ESR)

• Reference ranges for ESR are 0-15 mm/hr for males and 0-20 mm/hr for females.
• The test is performed by analyzing a tube of anticoagulated blood and measuring how many red blood cells settle to the bottom of the tube per hour in millimeters.
• The primary acute phase reactant responsible for the increased ESR is fibrinogen.
• Decrease in a previously elevated level of ESR is used to follow some diseases, such as polymyalgia rheumatica and temporal arteritis.

Autoimmune Disorders

• Autoimmune disorders are diseases caused by antibodies or lymphocytes produced against substances naturally present in the body.
• Associated genetic predisposition is common.
• Four common autoimmune disorders are:
  • Lupus (SLE)
  • Rheumatoid arthritis (RA)
  • Crohn's disease
  • Ulcerative colitis

Rheumatoid Arthritis (RA)

• RA is a systemic autoimmune connective tissue disorder that primarily affects the synovial joints.
• It affects 1% to 2% of the adult population worldwide and is predominantly a disease of young women.
• Joints of patients with RA make large amounts of IgG-RF and low amounts of normal IgG.
• Plasma cells in the circulation of patients with RA make almost exclusively IgG-RF.
• 60-70% of adults with RA have positive titers for RF, but only 33% are positive in the first three months of disease.
• Titers of RF are always measured, and the higher the titer, the more specific the test is for RA.
• Elevated titers of RF generally correlate with severity of disease.

Serologic Tests (Immunologic)

• Serologic tests focus on the immune component of the serum, looking at antigens or antibodies.
• Examples of serologic tests include:
  • Enzyme-Linked Immunosorbent Assay (ELISA)
  • Western Blot

Enzyme-Linked Immunosorbent Assay (ELISA)

• ELISA uses an antibody specific to the target protein that is tagged with an enzyme marker.
• The enzyme marker emits radiation, produces a color change, fluoresces under light, or simply emits light when antigen is present.
• ELISA can be used to detect the presence of an antigen or an antibody in a sample.
• It is also a useful tool for determining serum antibody concentrations.
• Because of high sensitivity, ELISA is a great screening tool for some conditions.
• Commonly used for many conditions, including HIV and Lyme disease.

Western Blot

• Western Blot can detect target proteins in quantities as low as 1ng due to high resolution of the gel electrophoresis and strong specificity.
• Often a confirmatory test.
• The membrane is "probed" with radioactive, or enzyme-tagged antibodies.

Nucleic Acid Amplification Test (NAAT)

• NAAT is not utilizing the antibody-antigen idea.
• It specifically detects pieces of the microorganism's genetic material (DNA or RNA), establishing its presence.
• Genetic material testing in ID attempts to shorten the time of detection, detecting organisms before the antibodies can be produced.
• NAAT has become commonplace in the clinical setting and is both highly specific and sensitive.
• Because NAAT testing is specific to a single organism, you need to be specific with your ordering of the test.
• A common example of when NAAT is used is in the diagnosis of Chlamydia infections (considered Gold Standard).

Diabetes and Lipid Testing

• Il existe diverse types de testes de glucosa, includite sero glucosa, teste de tolerancia glucosic, hemoglobina A-1c, glucosa urinari, glucosa postprandial, e glucagón, cada uno con su proprio scopo e rationales.

Diagnosis of Diabetes

• Un solo teste es insufficiente pro diagnosticar diabetes tipo 1 o 2; es necessari combinar duo del quatro testes sequente:
  • Hemoglobina A-1c ≥ 6.5%
  • Glucosa jejunum ≥ 126 mg/dl (o duo valores de 126 mg/dl)
  • Teste de tolerancia glucosic oral con duo valores > 200 mg/dl
  • Glucosa casual ≥ 200 mg/dl

Contraindications for Diabetes Testing

• Istos testes non debería esser efectuate quando le patiente es malade, severmente stressate, o ha recentemente stato sous steroides, pois le aumento del cortisol (endogene o exogene) causa un aumento del resistenzia insulinica.

Advanced Glycosylation Products (AGEs)

• AGEs son composto chimic que se forma cuando sucres se combina con aminoacidos o grasas, contribuente al danno diabetic e usate per diagnosticar diabetes e evaluar le nivel de controlo del diabetes.
• Hemoglobina A-1c (HbA1c) mesura le media del glucosa attachate al hemoglobina A (tipo I C) durante le vita del erythrocyte.

Antinuclear Antibody (ANA) Testing

• ANA testing is used for the diagnosis of Systemic Lupus Erythematosus (SLE) according to the American Rheumatologic Association criteria
• 4 or more of the following 11 criteria must be present at any time during the course of the disease:
  • ANA: complete test with double-stranded DNA, Smith, ribonucleoprotein, histone, and SS-A/Ro and SS-B/LA antibodies

Erythrocyte Sedimentation Rate (ESR)

• ESR measures the rate at which red blood cells settle at the bottom of a tube in an hour
• Reference ranges: 0-15 mm/hr for males, 0-20 mm/hr for females
• Increased ESR indicates inflammation, and a decrease in ESR indicates improvement in diseases such as polymyalgia rheumatica and temporal arteritis

Autoimmune Disorders

• Autoimmune disorders occur when the body's immune system produces antibodies or lymphocytes against substances naturally present in the body
• Associated genetic predisposition
• Common autoimmune disorders:
  • Lupus (SLE)
  • Rheumatoid Arthritis (RA)
  • Crohn's disease
  • Ulcerative colitis

Rheumatoid Arthritis (RA)

• RA is a systemic autoimmune connective tissue disorder that primarily affects the synovial joints
• Affects 1% to 2% of the adult population worldwide, predominantly young women
• Joints of patients with RA make large amounts of IgG-RF and low amounts of normal IgG

Anti-Citrullinated Peptide Antibody (Anti-CCP)

• Stands for anti-cyclic citrullinated peptide antibody
• Approximately 98% specific and 85% sensitive
• Good predictor of erosive disease (severe RA)
• Can be seen earlier in the disease process compared to RF

Enzyme Immunoassays (EIA or ELISA)

• Uses antibodies and antigens to detect the presence of an antigen or antibody in a sample
• Uses an enzyme marker that facilitates easy detection
• Can be used to detect the presence of an antigen or antibody in a sample
• Useful tool for determining serum antibody concentrations

Western Blot

• Uses electrophoresis to separate DNA, RNA, and protein fragments of antigens
• Then uses nitrocellulose or a similar membrane to detect the presence of specific proteins
• Often used as a confirmatory test

Nucleic Acid Amplification Test (NAAT)

• Detects pieces of the microorganism's genetic material (DNA or RNA) to establish its presence
• Highly specific and sensitive
• Used in the diagnosis of Chlamydia infections, considered the Gold Standard

Chemia e Bases de Testing

• Es importante pesar le beneficios contra le risicas - tests pote portar un risico de morbiditate/mortalitate
• Exemplos de tests con risicas:
  • Cerebral angiogram: conduce a stroke in 0.5% de casos

Error de Testing

• Fals positives: puede conducer a diagnoses incorrectes o tests additional unnecessarios
• Utilisa algoritmos de testing basate sur evidentia: proporciona orientamento per la selection de tests in specific disorderes e interpretacion de resultatos
• Pote reducer errors

Utilitates de Tests

• Screening
• Diagnostic
• Gestion de patientes:
  • Monitorage de levels de medicamentos (ex: acid valproic, warfarin, Tegretol)
  • Prevention de toxicitate (ex: lithium)

Rol del Clinico

• Decisiones raisonables: disponibilitate, information clinical, resultados clinical
• Pesa le risicas e beneficios
• Eligite sabiamente: evitar tests inutiles e tractamentos

Valores Criticos de Laboratorio

• Resultatos de tests que representa un stato pathophysiologic grave que pote esser mortal si non es tractate promptemente
• Debe esser reportate al provider intra 30 minutos
• Es normalmente highlightate in rubro o con un "C" al lado in le reporto

Rationaes de Testing

• Obtain sangue pro purposes diagnostic
• Screenar pro morbos
• Monitorar levels de medicamentos:
  • Determinar si es in un rang acceptabile (ex: acid valproic, warfarin, Tegretol)
  • Prevenir toxicitate (ex: lithium)
• Monitorar responsas a tractamento e interventiones
• Estabilir un prognosis
• Determinar doses de medicamentos effective (ex: PT/INR si le patiente prende warfarin)

Sensitivitate e Specificitate

• Sensitivitate: ability de un test de designar un individuo con le morbo como positive
• Specificitate: ability de un test de designar un individuo sin le morbo como negative
• Exemplos:
  • D-dimer: altissime sensitivitate, paupe predictive valor negative
  • CRP: sensibile ma non specific pro inflammation

Methodos de Collection de Sangue

• Sampling arterial: utilize pro identificar disorders metabolic, respiration, mixed acid-base
• Sampling venipuncture: methodo le plus commun de collection de sangue
• Sampling per punctura de pelle (fingerstick e heel stick): moins dolorose, reduc anxiety

Tubos de Collection de Vacuo

• Contiene un additive (ex: anticoagulante) que previne coagulation/coagulato del sangue
• Es importante de completarmente plenar le tubo e mixin le sangue con le additive per asegurar un ratio correcte de sangue a additive

Fontes de Error

• Insufficient mixing de sangue con le additive
• Sample clottate
• Insufficient sample
• Tube incorrecte
• Storage o etiquetatura incorrecte

Pannelles de Chemia

• Exemplos de tests de chemia:
  • Pannelle metabolic basic (BMP): evalua function renal e electrolytes
  • Pannelle metabolic comprehensive (CMP): BMP plus function hepatic e proteinas importante
  • Pannelle de electrolytes: helpful pro detectar problemas con fluidos e electrolytes
  • Pannelle de function hepatic: evalua function hepatic e detecta inflammation/danno hepatic

Diagnostico de Diabete

• Diagnosis requiere combinar multiple tests:

  • HgBA1C > 6.5%
  • Fasting BG > 126 mg/dL
  • Oral glucose tolerance test: duo valores > 200 mg/dL
  • Random BG > 200 mg/dL

• Non performar tests cuando le patiente es malade o severmente stressate

• Insulina: hormone polypeptide secretate per beta cellulas in isletas de Langerhans del pancreas

• Productos de glycosilation avanzate: resulting de reacciones chimic non enzymatic inter molecular que involucra glucosa e proteinas### Compuestos Quimicos de Dano por Diabetes

• Los compuestos quimicos se forman cuando el azucar se combina con aminoacidos o grasas y contribuyen al dano causado por la diabetes mellitus (DM) y se utilizan para diagnosticar y controlar la DM.

• Estos compuestos quimicos se miden con la prueba de HbA1C (hemoglobina glicosilada).

HbA1C (Hemoglobina Glicosilada)

• La prueba de HbA1C mide la cantidad de azucar unida a la hemoglobina A (tipo 1C) durante el ciclo de vida de un eritrocito (aproximadamente 3 meses).
• Puede ser influenciada por anemias, hemoglobinopatias, transfusiones y terapia farmacologica.
• El rango prediabetico es de 5.7-6.4%.
• La prueba de HbA1C puede ser realizada en el punto de atencion (POC) o en el laboratorio.

Fructosamina

• La fructosamina es un termino general para cualquier producto de glicosilacion avanzada que circula en suero.
• Determina el control de azucar en la sangre durante 2-3 semanas, basado en la vida media de la albumina y otras proteinas sericas.
• El rango normal es de 2-3 mg/dL.

Enzimas Hepaticas

Alkalina Fosfatasa (ALP)

• La ALP es una enzima presente en el higado, huesos, rinones, placenta y intestino.
• Tiene dos isoenzimas circulantes principales: hueso y higado.
• Un aumento en la ALP puede indicar dano hepatico o obstructcion intrahepatica.
• El rango normal es de 20-70 U/L.

Aspartato Aminotransferasa (AST)

• La AST es una enzima que se encuentra en el citosol y las mitocondrias de los hepatocitos.
• Tambien se encuentra en musculos estriados, rinones, cerebro, pancreas, pulmones y leucocitos.
• Un aumento en la AST puede indicar inflamacion de los hepatocitos.
• El rango normal es de 9-20 U/L.

Alanina Aminotransferasa (ALT)

• La ALT es una enzima que se encuentra en el citosol de los hepatocitos.
• Es un indicador mas especifico de lesiones hepaticas que la AST.
• Un aumento en la ALT puede indicar inflamacion de los hepatocitos.
• El rango normal es de 8-20 U/L.

Sensibilidad de AST y ALT para la Enfermedad Hepatica

• La ALT es mas especifica para la enfermedad hepatica que la AST.
• La normalidad de los niveles de transaminasas no excluye la presencia de enfermedad hepatica.
• La gravedad de la elevacion de los niveles de transaminasas no se correlaciona con la extension del dano.

eGFR (Tasa de Filtracion Glomerular Estimada)

• La eGFR es una medida de la funcion renal.
• Se utiliza para clasificar la enfermedad renal en 5 estadios, desde el estadio 1 (daño renal con GFR normal o alta) hasta el estadio 5 (insuficiencia renal severa).

Fasting BG (Glucosa en Ayunas)

• La prueba de glucosa en ayunas requiere un ayuno de 8-12 horas.
• El rango normal es de 70-100 mg/dL.
• Un resultado de >126 mg/dL puede diagnosticar DM.