INTERPRETATION OF LAB TESTS

1. INTERPRETATION OF LAB TESTS Barb Bancroft, RN, MSN www.barbbancroft.com BBancr9271@aol.com

2. Rule number one … • Know your own lab’s normal values • Various methods of testing and various “normal ranges”…

3. List the plasma proteins 1) albumin 2) globulins 3) fibrinogen Is there a difference between serum proteins and plasma proteins? Serum protein electrophoresis

4. Yes. • The removal of fibrinogen = serum. • So, the serum proteins are albumin and the “globulins”. • Fibrinogen—(1.5-4.0 g/dL or 150 to 400 mg/dL) • hyperfibrinogenemia (greater than 400 mg/dL) increases the risk of clotting • What conditions increase the risk of clotting?

5. Estrogen excess increases fibrinogen • COC’s? • HT? (hormone therapy) • Endogenous estrogen?

6. Smoking increases fibrinogen • So how about smoking and estrogen, eg, oral contraceptives or HT in the PMF? • Aging and fibrinogen—increases by 1% per year after age 30

7. Biological Rhythms and clotting • Liver produces clotting factors and inflammatory mediators primarily at night; kicks them out in the a.m. • Adrenal gland produces cortisol and epinephrine in a.m. increasing blood sugar and making platelets “sticky” • MI (arterial clot or white clot)—inflammation (inflammatory mediators are highest in the a.m.) triggers plaque rupture; platelets are stickiest in the early a.m. due to highest blood sugar; platelet plug forms, triggers clotting cascade; takes 2 hours to form; MI at 9 a.m. • ASA inhibits platelet aggregation • Coumadin/Heparin inhibit clotting factors

8. DIC (Disseminated Intravascular Coagulation) • Overutilization of platelets and clotting factors • Microvascular clots formed shutting down organ systems—kidneys, lungs, brain • Platelet counts falling; clotting factors decreasing • After fibrin clots are formed, fibrinolysis occurs • FSPs (fibrin split products), FDPs (fibrin degradation products), D-dimers • What triggers DIC?

9. Total Serum Proteins • Albumin • Globulins • (Albumin comprises 2/3 of the total serum proteins; globulins 1/3) • Total serum protein (TSP) • A/G ratio • Generally used as screening tests altho’ the albumin level can be used to determine nutritional status and or prognosis in liver disease

10. Serum Protein Electrophoresis—based on molecular weight and overall charge (positive or negative) • + - Well in the gel Electrical current running through gel

11. Serum electrophoresis albumin globulins β α1 α2 Γ

12. Albumin • Functions—holds water in the vascular space • Binds drugs (protein-bound vs. “free” drug) • Hypoalbuminemia (less than 3.0 g/dL)--what are the causes? • Liver disease—decreased synthesis • Or leaky kidneys…

13. Kidney disease • Nephritis—1-2+ protein in the urine • Nephrosis—3-4+ protein in the urine • Protein in the urine is usually albumin—macroalbuminuria with 1+-4+ • “Early” and reversible kidney disease in the diabetic or hypertensive patients is manifested by spilling “microalbuminuria” • TREAT with “PRILS”-ACE INHIBITORS

14. “Prils”—The ACE inhibitors (Brazilian pit viper) • Captopril (Capoten) • Enalapril (Vasotec) • Lisinopril (Prinivil, Zestril) • Perindopril (Aceon) • Moxepril (Univasc) • Benazepril (Lotensin) • Quinapril (Accupril) • Trandolapril (Mavik) • Ramipril (Altace) • Etc…

15. “Angie” and the healthy kidney… • Afferent arteriole (vasodilated via (prostaglandins) • Blood entering glomerulus • Glomerulus→filter • Efferent arteriole (vasoconstricted via (angiotensin 2) • Blood exiting glomerulus PG filter AT2 Toilet

16. “Angie, the “prils” and the Diabetic/hypertensive Kidney…hyperglycemia/HTN • Afferent arteriole (  vasodilation by (  prostaglandins) • Blood entering glomerulus • Glomerulus→filter • Efferent arteriole (  vasoconstriction via (  angiotensin 2) • Blood exiting glomerulus Microalbuminuria**

17. The elderly • The 1% rule • The process of senescence begins at ___? • 1% decline in function per year in organ systems such as the liver (major exceptions are clotting factors and the size of the prostate) • Serum albumin in the elderly • Decreased binding sites for drugs—increased bioavailability of drugs and drug toxicity

18. The globulins… The alpha 1 globulins— • alpha one antitrypsin • High-density lipoprotein—the good guy • HDL’s clear excess cholesterol from the blood; HDL’s are also potent “anti-oxidants” and prevent LDL from oxidizing; the HDLs are also potent “anti-inflammatory” lipoproteins; keep levels above 40 mg/dL (1.04 mmol/L) and above 60 mg/dL (≥ 1.55 mmol/L) would be ideal • For every 5 mg/dL (0.13 mmol/L) decrease in HDL below the mean, the risk of CHD increases by 25%

19. So if HDLs are good for you, how can we boost HDLs? • Eat right— garlic, beans, omega-3 fatty acids, fiber, almonds (and other nuts), plant stanols (Take Control, Benechol, Smart Balance) • Decrease saturated and trans fats

20. What else boosts HDLs? • Exercise • Estrogen • Ethanol

21. So, what’s my motto? • Run a mile, drink a beer, pop a Premarin… • Have a nice glass of wine with almond-crusted salmon with my Mom… • OR…

22. Increasing HDLs • Decrease carbohydrate intake (modified Atkin’s diet) • Say YES to drugs… • Niacin/Niaspan boosts HDL the most—up to 25% • Drugs— the “statin” sisters (mostly lower LDL)-- (simvastatin/Zocor, rosuvastatin/Crestor)**, atorvastatin (Lipitor), fluvastatin/Lescol, pravastatin/(Pravachol) • Metformin (Glucophage) increases HDLs • The “glitazones” increase HDLs

23. Alpha-2 globulins • Transport proteins—transferrin (iron), Thyroid binding globulin (TBG), ceruloplasmin (copper)

24. Beta globulins—the bad guys • LDLs (low density lipoproteins)—directly deposit into the walls of the arteries via the process of oxidation, forming atherosclerotic plaques • The higher the LDLs, the greater the risk for plaque formation and atherosclerosis

25. New guidelines—with CAD or a risk equivalent (diabetes), the LDL should be 70 mg/dL • For the rest of us with other risk factors—100 mg/dL (<2.85 mmol/L) • Unless you’re perfect…--130 mg/dL (<3.37 mmol/L)

26. Risk factors for increased LDLs • Family history • Diet high in trans fats and saturated fats • Smoking • High iron levels (increases oxidation) • High insulin levels • Couch potato • Fat around the middle

27. LDL reduction • Estrogen?? Exercise? Eat right? • Foods; fiber; almonds; plant stanols • Nix red meat, sat fats and trans fats

28. Say YES to statins—the “statin” sisters… • Say yes to the “statin” sisters—lova (Mevacor), atorva (Lipitor), prava (Pravachol), simva (Zocor), fluva (Lescol), rosuva (Crestor) • Statins are anti-inflammatory, anti-lipid, decrease plaque formation, stabilize plaques, prevent plaque rupture

29. VLDL (very low density lipoproteins)--triglycerides • If the fasting triglyceride level is 500 mg/dL, the postprandial TGs are 1000 mg/dL • Reduce refined sugars and alcohol • The role of niacin, and the fibrates, Lopid or Tricor; bile acid sequestrants (Questran, Wellchol) • Ideal is less than 150 mg/dL (1.70 mmol/L) • Borderline high is 150-199 (1.70-2.25 mmol/L)

30. Total cholesterol—screening purposes only—best to do the LIPID PROFILE • Lipid profile after an 8 to 12 hour fast • Patient with triglycerides above 250 mg/dL (2.81 mmol/L) (and an HDL less than 40 mg/dL (1.04 mmol/L)—THINK… 1) Type 2 Diabetes (check the fasting blood sugar) 2) Hypothyroidism (TSH) (0.4-4.2 μU/mL or mU/L) for 21-54 yo; 0.5-8.9 μU/mL or mU/L for 55-87)

31. WBC and DIFFERENTIAL • 5 types of mature WBC’s and one immature WBC circulate in the “cold, cruel world” known as peripheral blood • Normal range 5,000 to 10,000 (3500-12000)

32. The List… • Segs (poly, PMN, segmented neutrophil)(57-63%) of the total white count; acute inflammation, bacteria (1.51-7.07) Bands (0-4%) (0.00-.51)—precursor to the seg THE SEGS + BANDS as a % of the TOTAL WBC is the ANC (Absolute Neutrophil Count) • Lymphocytes (30%)-first responder to viruses; cells of the immune system (0.65-2.8) • Monocytes (4%)—cells of chronic inflammation (0.00-0.51) • Eosinophils (3%)—cells that respond to parasites and allergies (0.00-0.42) • Basophils (less than 1%)—who cares? Contain histamine (0.00-0.16)

33. The granulocytes… • All of the cells with the last name “phil” are called granulocytes • The neutrophils are most important—acute inflammation, acute necrosis—phagocytic • The eosinophils are increased in allergic responses and with parasitic infections (Carlotta) • Basophils—allergies and anaphylaxis

34. 5 types of WBCs • Segs—(phagocyte) its only job in the world is to EAT until it dies • Cell of acute inflammation • First responder to bacterial invasion • Loves acute necrotic tissue • 57-63% of total WBC (1.51-7.07)

35. How do segs grow up? • Stem cells • Myeloblast (BM) • Promyeloctye (BM) • Myelocyte (BM) • Metamyelocyte (juvenile) (BM) • Band neutrophil (BM and PB) • Segmented neutrophil (BM and PB)

36. Segs are produced in about 8-10 days; leave the bone marrow and live in the blood for 5-6 hours; migrate into tissues and eat for 36-72 hours; • released rapidly in response to virulent organisms such as strep, staph, E. Coli, H. flu, meningococcus, Pseudomonas • Acute necrosis—MI, gangrene of the bowel, acute appendicitis

37. Shift to the left • During the time of acute need, the bone marrow is functioning overtime…massive production results in a partial loss of quality control concerning the immaturity of the cells that are released into the peripheral blood • WBC and diff will show an increased number of segs and bands and maybe even a metamyelocyte or two— • shift toward immaturity • Shift-to-the-left—increased number of bands • What is the usual number of bands? 0-4% • Bands and SIRS—the systemic inflammatory response syndrome

38. Clinical conditions with an increased WBC and “shift-to-the-left” • GABHS • Pyelonephritis • Acute appendicitis • Bacterial meningitis

39. Drugs and neutropenia • Chemotherapy (all patients) • Cimetidine (Tagamet), ranitidine (Zantac) • Carbamazepine (Tegretal); phenytoin • Captopril (Capoten), enalapril (Vasotec), amiodarone, quinidine • Zidovudine (Retrovir) • Clozapine (Clozaril) • Metronidozole (Flagyl) • Gentamicin, clindamycin, imipenem, PCNs, tetracyclines • Azothiaprine (Imuran) • PTU

40. The Absolute Neutrophil Count (ANC) • % segs + %bands x total WBC • 57% segs (5.7) + 3% (0.3) bands x 10,000 = 6,000 (6.0) • Neutropenia is defined as an ANC less than 1000 (1.0)—various degrees of neutropenia—from bad to worse to “worser”  • Neulasta (G-CSF)(Granulocyte Colony Stimulating Factor)

41. SEGS…normal function • Margination, pavementing, migration, engulfment, and degranulation (releasing enzymes) Yum.

42. Prednisone and the neutrophil • Inhibits migration and degranulation, hence its anti-inflammatory properties • Prednisone also increases blood sugar due to glycogenolysis (metformin can be used to inhibit glycogenolysis) • High blood sugars inhibit the function of segs • Diabetes– Blood glucose greater than 180 mg/dL (9.99 mmol/L) inhibits seg migration (normal blood glucose is 74-106 mg/dL or 4.1-5.9 mmol/L) • Elderly with decreased migration of segs, increases infection susceptibility • Fever increases the migration of segs—is fever good for you? YES!

43. STRESS! • Stress and the WBC • Screaming kids • 24-hours post-op • Last trimester of pregnancy • No bands

44. Inflammation—lab tests • C-reactive protein -- < 1 mg/dL or < 10 mg/L; the CRP is an acute phase reacting protein; rapid, marked increases occur with inflammation, infection, trauma, tissue necrosis, malignancies, and autoimmune diseases • Increases quickly and dramatically in response to stimuli, and decreases substantially with resolution of the disorder

45. hs-CRP—low levels of inflammation in the vascular system • High sensitivity assay indicates a high risk of vascular inflammation and subsequent cardiac risk • Use of hs-CRP + lipid values together are more accurate at predicting risk than lipid studies alone • Inflammatory mediators, IL-6 and TNF-α are produced within unstable plaques as well as from adipocytes in abdominal fat, which in turn increases hs-CRP production by the liver • The bigger the waistline the greater the hs-CRP • YIKES…so what should your waistline be? • Ridker PM et al. N Engl J of Med 2000; 342:836-43; Ridker PM et al. N Engl J of Med 1997;336:973-9)

46. What can reduce hs-CRP? • Exercise • Loss of abdominal fat • Statins • “glitazones”—rosi- and pio- • Aspirin • Omega-3 fatty acids • Nuts • The Mediterranean diet is anti-inflammatory

47. Inflammation—the sed rate • Sed rate—rate of the settling of RBCs in anticoagulated blood; low sensitivity and specificity; many factors can influence the sed rate • Newborn—1-2mm/hr • Neonates and children—3-13 mm/hr • Post adolescent male (less than 40 years)—1-15 mm/hr • Post-adolescent female (less than 40 years)—1-20 mm/hr • Over forty years—the maximum normal ESR at a given age is: Males age in years/2; Females age in years + 10/2

48. Monocyte/Macrophage • Monocyte in blood, macrophage in tissue (Kupffer cell in liver, microglial cell in brain) • Phagocytes that respond much slower than the seg (2-4 days vs. 5-10 minutes for the seg) • Eats for months • Cell of chronic inflammation

49. Chronic inflammation--TB • Many chronic inflammatory conditions have the last name “osis” • Tuberculosis, sarcoidosis, histoplasmosis, amyloidosis • “red snappers”—the tubercle bacillis • Macrophages circling and containing the bacillis and keeping it “in check” or dormant • Granulomas—histologic appearance of macrophages “circling the wagons” so to speak

50. Macrophages and Vitamin D • “If you have consumption, go up on the mountain…”