Clinical chemistry Clinical chemistry (also known as clinical biochemistry, chemical pathology, medical biochemistry or pure blood chemistry) is the area of pathology that is generally concerned with analysis of bodily fluids. Diabetic Workup Normal Serum Glucose (Fasting) Pathology 70 – 110mg/dL >126mg/dL (Diabetes Mellitus) Criteria 1 500 – 700 mg/dL (Ketoacidosis) <50mg/dL (Hypoglycemia) Random Blood Glucose OGTT 3 (after taking 75 mg glucose) <200mg/dL >200mg/dL <140mg/dL HbA1c Criteria 2 >200mg/dL <7% >8% Criteria (not diagnostic) Indicating Diabetic Nephropathy Urine Albumin 0 >30mg/day (microalbuminuria) >300mg/day (macroalbuminuria) Liver Function Tests 1. Hepatocyte Injury Normal AST (10-40 U/L) upto 40 U/L ALT (9-60 U/L) upto 40 U/L LDH Pathological 2. Billiary Excretory Function Serum Billirubin Total <1.2mg/dL Direct 0–0.3 mg/dL >2.0mg/dL Indirect Serum Alkaline Phosphatase gammaGlutamyl Transpeptidase (30 – 120 IU/L)upto 70 U/L 0 to 51 IU/L 3. Hepatocyte Function Serum Albumin 3.9 – 5.0 g/dL Prothrombin Time 12–15 seconds (raised in chronic liver disease) INR 0.8–1.2 Serum Ammonia 10-80 ug/dl Note : AST > ALT ; alcoholic hepatitis ALT> AST ; viral hepatitis An increased levels of direct bilirubin and alk. Phosphatase (with normal indirect bilirubin and normal Hb) is always jaundice secondary to extrahepatic obstruction. Eg. A 54 year old man presents with high fever, jaundice and colicky abdominal pain in the rt. Upper quadrant (this is classic Charcot’s triad ). The gall bladder can not be palpated ( this excludes carcinoma of the head of the pancreas by Courvoisier’s Law) workup reveals Hb 15.3mg/dL, unconjugated bilirubin level 0.9mg/dL, conjugated bilirubin level of 1.1mg/dL and Alk.phosphatase level of 180 IU/L/ which of the following is the diagnosis. a. b. c. d. e. Acute cholecystitis Chronic cholecystitis Bileduct obstruction by stone Carcinoma of gallbladder Carcinoma of the head of pancreas Jaundice Jaundice Type Hepatocellular Obstructive Hemolytic Hyperbilirubinemia Conjugated/Unconjugated Conjugated Unconjugated Urine Bilirubin ↑ ↑ Absent Urine Urobilinogen Normal/↓ ↓ ↑ Enzyme Markers Serum Enzyme Diagnostic Use AST/ALT Viral Hepatitis, Alcoholic Hepatitis, MI (AST) GGT to find whether ALP is raised elevated even in subclinical liver dysfunction, it is used In biliary or extrabiliary disease. ALk.Phosphatase Obstructive Liver Disease, Bone Mets. Amylase/Lipase Acute Pancreatitis Markers of Viral Hepatitis (raised levels indicate) (SEQ point of view) Hepatitis A IgM anti HAV indicates new infection IgG anti HAV indicates old infection (obtained by Total Anti HAV – IgM anti HAV) Hepatitis B HBsAg HBsAb (anti HBsAg) HBeAg indicates infection indicates immunity indicates viral activity HBeAb (anti HBsAg) peak of infection; indicates waning IgM anti HBcAg indicates new infection IgG anti HBcAg indicates old infection (MCQ point of view) HBsAg HBeAg IgM anti HBcAg IgG anti HBcAg IgG HBsAb HBV-DNA Acute Infection + + Window Period* + Previous Infection + + Immunization + Chronic Infection + + + * Window Period is defined as the timeperiod in which the HBsAg disappears and the HBsAb appears. eg. A 27 year old man with a history of IV drug use is seen in the emergency department because he has experienced nausea, vomiting and passage of dark coloured urine for the past week. Physical examination shows scleral icterus and mild jaundice. There are both recent and healed track marks in the right antecubital fossa. Neurological exam shows a confused, somnolent man oriented only to person. He exhibits asterixis. Lab studies show: Total Protein 5.0g/dL Albumin 2.7g/dL AST 2342 U/L ALT 2150 U/L Alk.Phos. 233U/L Total bilirubin 8.3 mg/dL Direct bilirubin 4.5 mg/dL HBsAg Positive Anti HBs Negative Anti-Hbc positive Anti-HBc IgM negative Anti HAV negative Anti HCV negative Anti HDV positive Which is the likely diagnosis a. Acute HBV infection b. Chronic HBV infection c. Acute HAV infection d. Acute Co infection of HBV and HDV e. Superinfection of HBV with HDV From the clinical picture itself it is obvious that the person has HBV due to IV abuse. Also if you look at the workup you will find that Anti HBc IgM is negative which means there is previous infection with HBV, besides Anti HDV is positive too which means the answer is e.). AST>ALT. it cud be b.) but e.) is more likely. Anti HAV is negative that rules out c.). for acute co-infection anti HBc Ig M shud be positive. Cardiac Workup (ENZYMES) Troponin (cTn1) CPK-MB LDH 1 SGOT Increases in (after chest pain) (in hours) 4-6 4-8 10-12 Peaks at (in hours) 12-24 12-24 2-3 days Wanes in (in days) 3-10 3-4 7-10 Normal Value NV (in IU/L) 0-0.1 (ng/mL) 250 230-460 5-40 Examples 1. A 60 year old male presents with acute retrosternal chest pain to the emergency department. Lab investigations show total CK 360 U/L (NV : upto 195U/L) CK MB 32 U/L, SGOT 54 U/L, LDH 418 U/L. ECG was consistent with Acute MI. What is the possible duration of his present attack? a. 30 minutes b. 2 hours c. 12 hours d. 36 hours e. 5 days Here Total CK is elevated means that there has been atleast greater than 4 hours to the injury, CK MB is normal (with this u have to look at LDH or SGOT) means that it has peaked nd is now waning or did not increase in any case it wud peak at 12 hours. Now LDH is elevated and it increases at 12 hours. So using both these values the answer is c.) 2. A 45 year old male experiences crushing substernal chest pain on arriving at work in the morning. Over next few hours the pain persists and begins to radiate to his left arm. He becomes diaphoretic and short of breath, but he waits till the end of his 8 hours shift to go to the hospital. Which of the following serum lab test finding is most useful to diagnose his condition on admission to hospital? a. Elevated lipase b. Elevated AST c. Elevated CK-MB d. Elevated LDH e. Elevated troponin Ans. C.) Note I cud not find times for SGOT(AST), because it is a redundant test and is now no longer used for cardiac workup. It is replaced by troponin. Troponin values are measured from a graph based on multiples of cut off values that range from 50-100 during injury. Myoglobin is a recent marker (10 – 95ng/mL) increases in 1-3 hours peaks at 6-10 hours and wanes in 12-24 hours. TUMOUR MARKERS Prostate Specific Antigen (PSA) used to screen for Prostate Carcinoma >1ng/mL Cancer < 1ng/mL BPH Prostatic Acid Phosphatase CarcinoEmbryonicAntigen (CEA) produced by 70% of colorectal and pancreatic carcinomas, also by gastric and breast carcinomas Alpha Fetoprotein HepatoCellular Carcinoma Non seminomatous Tumours of the Testis (Endodermal Sinus Tumour aka Yolk Sac Tumour) Beta HCG Hydatidiform Mole, Choriocarcinomas, Gestational trophoblastic tumours CA-125 Ovarian Cancer Alkaline Phosphatase Mets. To bone, Paget’s disease Examples. 1. During routine exam of a 70 year old male the prostate is found to be normal in size on palpation. He has serum PSA 17ng/mL. a routine urinanalysis reveals no abnormalities. He is healthy with H/O no major illness. Which of the following histologic finding is seen on prostate biopsy a. Hyperplastic nodules of the stroma and glands lined by 2 layers b. Poorly differentiated glands lined by a single layer of epithelium and packed back to back c. Foci of chronic inflammatory cells in the stroma and in normal appearing glands d. Areas of liquefactive necrosis e. Multiple caseating granulomas Answer. B.) bcos PSA levels indicate cancer. 2. A 70 year old man C/O nocturia, urinary urgency and a feeling that he could not completely empty his bladder. A digital exam reveals a firm enlarged prostate. Bone scan is ordered and shows positivity in multiple vertebral bodies. Elevtion of which of the following substances would be most strongly associated with development of bone lesions. a. PSA b. Prostatic acid phosphatase c. Alk.Phosphatase d. Tartrate Resistance Acid Phosphatase e. Urinary hydroxyl proline Answer. C.) TRAP is elevated in hairy cell leukemia. Renal Function Tests Urinalysis Serum creatine 0.6-1.5 mg/dL Serum Urea (BUN) 8-25 mg/dL Increased BUN is, by definition, azotemia. It is due either to increased protein catabolism or impaired kidney function Increased protein catabolism results from: a really big protein meal severe stress upper GI bleeding Impaired kidney function may be "prerenal", "renal", or "postrenal". Prerenal azotemia results from underperfusion of the kidney: dehydration, hemorrhage, shock, congestive heart failure Renal azotemia has several familiar causes: acute tubular necrosis, chronic interstitial nephritis, some glomerulonephritis Postrenal azotemia results from obstruction of urinary flow: prostate trouble, stones, surgical mishaps, tumors Decreased BUN Lack of protein (celiac disease, some patients with nephrotic syndrome) Severe liver disease (end-stage cirrhosis, yellow atrophy, really bad hepatitis, halothane or acetaminophen toxicity, enzyme defects) Overhydration (iatrogenic, psychogenic water-drinking) Ability to concentrate urine based on hygrometer, refractometer, or dipstick. Less Significant Pituitary Prolactin Corticotropin Thyroid Function Tests 2 -30 ng/mL TSH 0.3 to 3 mIU/ml T4 4 - 11 mcg/dL Free T4 0.8 to 1.7 mcg/dl T3 97 to 219 ng/dl Free T3 210 to 440 pg/dl Thyroid binding globulin Albumin Iodine Uptake Diseases TSH Primary Thyrotoxicosis decreased T3 increased T4 increased Secondary Thyrotoxicosis increased increased increased T3 thyrotoxicosis undetectable increased decreased Primary Hypothyroidism increased decreased decreased Hashimoto’s normal decreased Parathyroid Calcium 8.5 to 10.2 mg/dL PTH 10-60 pg/ml Primary Hyperparathyroidism -inc. PTH, inc. serum Ca2+ Secondary Hyperparathyoidism -inc.PTH, hypocalcemia with hyperphosphatemia Adrenal Cortex ACTH Cortisol Exogenous Glucs. Dec. inc. Cushing’s Disease inc. inc. Acute Adrenocort. Insuf.. inc. dec. Addison’s inc. dec, with hypercalcemia, hypoglycemia, hyponatremia, hyperkalemia, eosinophila, metabolic acidosis Secondary Insuf.. By Muhammad Usman Zafar 4th year MBBS SIMS Batch 2005-10 inc. may respond to ACTH test