We Are Biochemical Factories

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We Are Biochemical Factories

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1. We Are Biochemical Factories Each organ system can be thought of as a biochemical factory with organ-specific products These products may be monitored biochemically as a measure of organ system health/function Specimens containing these products include: Blood Urine Pleural/ascites fluids Saliva

3. Reference Ranges RR are the range of values (results) found in healthy normal individuals. These are established by testing many people and plotting the results on a curve A mean and standard deviation can be determined, but not all results can be described neatly by a Gaussian distribution At the extremes of the normal results, there may even be overlap with results from “sick” populations

4. RR and Specific Groups Cannot assume that RR are good for all people There are expected differences for: Age (newborn, children, elderly) – Alk. Phos. Sex (Hgb in women) Factors that influence results: Pregnancy Exercise Diet Tobacco use Altitude Medications

5. Indications for Lab Study To confirm a clinical impression (glucose for DM, Hgb for anemia) To rule out disease/diagnosis (pregnancy test to rule ectopic pregnancy in case of abdominal pain) To provide therapeutic guidance (PTT in anticoagulation therapy) To screen for disease (least valid reason, but notable exceptions – premarital VDRL, newborn screens, blood donor lab screening)

6. Panel Testing Panels of biochemical tests are constructed for each organ, organ system or group of organ systems A common routinely used panel includes 20 tests to monitor: Kidneys Liver Bone Muscle Heart related risks Fluids/electrolytes Nutrition

8. Panel testing Many additional tests and panels are in use to provide more detailed information when appropriate Patterns of initial panel results can provide an experienced clinician with direction in subsequent workup.

9. Stat and Panic Values Fast turnaround time (often less than 1 hour) to modify therapy: Glucose in diabetic ketoacidosis Drug levels such as theophylline Amylase in suspected pancreatitis Troponin in suspected MI and many others

10. Out of range (Panic) values Sometimes the result is so out of range as to be life threatening The lab must then immediately contact clinician with result, whether ordered “stat” or not These “panic values” are confined to a list of analytes with potential to be lethal if left unchecked for a short period

11. A Few Common Panic Values Hematology: Hct <14% Platelets <20,000/microliter PTT >40 seconds Chemistry: Ca <6 mg/dl, or >13 mg/dl Na <120 mEq/L, or > 160 mEq/L Arterial pH <7.2, or >7.6 Microbiology: Blood culture positive Gram stain on CSF or other body fluid positive

12. Some information on proper collection Lavender top (EDTA anticoagulant): whole blood CBC (complete blood cell count) = RBC + WBC + Platelets Erythrocyte Sedimentation Rate (ESR)

13. Some information on proper collection Blue top (citrate anticoagulant): plasma for coagulation tests Prothrombin Time (PT) Activated Partial Thromboplastin Time (APTT; PTT) Thrombin Time Fibrinogen Factor assays

14. Some information on proper collection Gray top (fluoride inhibits cellular glycolysis): for accurate glucose measurements to diagnose diabetes mellitus Green top (heparin): plasma for stat chemistries (electrolytes, basic metabolic panel, cardiac injury markers) Other body fluid containers: urine, cerebrospinal fluid, ascites fluid, pleural fluid

15. Case 1 A 47-year-old man experienced acute onset of intense chest pain radiating from midsternum into his left arm and left jaw. The pain began about 30 minutes earlier. He had had many episodes of epigastric pain over the last few years that responded to antacids; however, this pain was much more severe and crushing. He was 30 pounds overweight and smoked two packs of cigarettes per day. Earlier in the day he had worked strenuously digging in his garden. His mother was alive and well, as were three siblings. His father had died suddenly on a business trip at 49 years of age.

16. Differential Diagnosis Acute Myocardial Infarction (AMI) Pulmonary Embolus (PE) Intercostal muscle spasm Vascular accident (e.g., aneurysm) Broken rib Pulmonary abnormality

17. Tests to be performed in the ER Myoglobin CK-MB Cardiac Troponin I (or T)

18. Treatment for AMI Fibrinolysis (TPA) Angioplasty Heparinization

19. Tests to be performed to monitor acute therapy PT  APTT Basic Metabolic Panel

20. Tests to be performed to assess cardiac risk Total cholesterol HDL cholesterol Triglycerides LDL cholesterol Maybe homocysteine in the future

21. Case 2 A 35-year-old man drove straight through from Miami to Richmond during which time his right calf became progressively more tender and swollen. After a brisk walk the next morning, he had sudden onset of chest pain that persisted, and a few hours later he coughed up some blood.

22. Differential Diagnosis Thrombophlebitis and pulmonary embolus Leg muscle injury/fasciitis/cramp Pneumonia/lung infection Traumatic injury

23. Tests Ventilation-perfusion scan of lungs--decreased flow due to embolus Doppler study of blood flow in leg--obstruction (clot) to flow can be detected

24. Treatment heparin converting to coumadin after a few days

25. Lab Monitoring APTT for heparin PT for coumadin; reported as the INR = (PTpatient/PTcontrol)ISI

26. Labs for Risk Assessment Protein C Protein S Activated protein C resistance (APCR) Lupus anticoagulant How long should he stay on coumadin? Does coumadin affect what his dentist does?

27. Case 3 A 3-year-old girl had a fever of 104°F, complained of ear ache, and was extremely lethargic. She had had a cold for the last week.

28. Differential Diagnosis Upper respiratory infection (URI) Otitis media Other infectious source--urinary tract, intestine, CNS

29. Lab tests CBC showed WBC 13.5 x 109 cells/L (elevated) with 38% granulocytes, 12% bands, 40% lymphocytes, 10% monocytes Urinalysis--dipstick positive for nitrite, positive for leukocyte esterase microscopic showed numerous WBC, loaded with bacteria Throat smear--negative for bacterial antigens (Streptococcus); sent for culture Neurological exam--normal GI--no diarrhea; abdomen soft and non-tender except in lower region near bladder

30. Case 4 A 39-year-old woman complained of "not feeling very good" for the last year. She gave a history of heavy menstrual periods. Her oral mucosa and nail beds were very pale.

31. Differential Diagnosis Iron deficiency anemia Diabetes mellitus Electrolyte abnormality Occult malignancy Pregnancy

33. Anemia The anemia responded to oral Fe. She was found to have enlarging fibroid tumors of the uterus that were eventually removed surgically. She had three units of packed RBCs transfused. She did well post-operatively. At age 52 she again reported "not feeling good" for at least a year. Physical exam showed yellow skin and sclerae of the eyes.

34. Liver Panel

35. Liver Biopsy Hepatitis C RNA in serum by quantitative RT-PCR

36. Treatment Alpha interferon ribavirin liver transplant

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