INTERPRETATION OF LAB TESTS

1
INTERPRETATION OF LAB TESTS

• Barb Bancroft, RN, MSN
• www.barbbancroft.com
• BBancr9271_at_aol.com

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Rule number one

• Know your own labs normal values
• Various methods of testing and various normal
  ranges

3
Serum protein electrophoresis

• List the plasma proteins
• 1) albumin
• 2) globulins
• 3) fibrinogen
• Is there a difference between serum proteins and
  plasma proteins?

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 g/dL)
  increases the risk of clotting
• What conditions increase the risk of clotting?
  Obesity, venous stasis, hip and pelvic surgery,
  immobility, age

5
What else?

• Endogenous estrogen?
• Estrogen excess increases fibrinogen
• Combined oral contraceptives? The old days vs.
  todays COCs
• HT? (hormone therapy)
• Dose dependentage dependent
• Aging and fibrinogenincreases by 1 per year
  after age 30

6
What else?

• Smoking increases fibrinogen
• So how about smoking and estrogen, eg, oral
  contraceptives or HT in the PMF?
• Use the patch! Or an IUD

7
Biological Rhythms and clotting

• Liver produces clotting factors overnight
• Clotting factors are highest in the a.m.
• DVT (venous clot or red clot) is formed breaks
  off in early a.m. and travels to lungsPulmonary
  embolism at 730 a.m.
• 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
Total Serum Proteins

• Albumin
• Globulins
• (Albumin comprises 2/3 of the total serum
  proteins globulins 1/3)
• A direct albumin level can be used to determine
  nutritional status and/or the prognosis in liver
  disease

9
Serum Protein Electrophoresisbased on molecular
weight and overall charge (positive or negative)

• 
  -

Well in the gel
Electrical current running through gel
10
Serum electrophoresis
albumin
globulins
ß
a1
a2
G
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Albumin

• Functionsholds water in the vascular space
• Binds drugs (protein-bound vs. free drug)
• Hypoalbuminemia (less than 3.0 g/dL or 30
  g/L)what are the causes?
• Liver diseasedecreased synthesis due to liver
  disease or due to an OLD liver(1 rule)
• Or leaky kidneys

12
Patient with ascites?

• SAAGserum ascites/albumin gradient
• SAAGalbuminserum / albuminascites
• ratio greater than 1.1 is 97 predictive of
  portal hypertension as the cause of ascites
• SAAG less than 1.1 is nonportal
  hypertensionnephrotic syndrome, infection (TB,
  fungal, CMV), pancreatic ascites, ovarian cancer,
  peritoneal carcinomatosis

13
Kidney disease

• Nephritis1-2 protein in the urine
• Nephrosis3-4 protein in the urine
• Protein in the urine is usually
  albuminmacroalbuminuria 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
PrilsThe ACE inhibitors

• Captopril (Capoten)
• Enalapril (Vasotec)
• Lisinopril (Prinivil, Zestril)
• Perindopril (Aceon)
• Moxepril (Univasc)
• Benazepril (Lotensin)
• Quinapril (Accupril)
• Trandolapril (Mavik)
• Ramipril (Altace)
• Etc

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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
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Angie, the prils and the Diabetic/hypertensive
Kidneyhyperglycemia/HTN

• Afferent arteriole
• ( ? vasodilation by
• ( ? prostaglandins)
• Blood entering
• glomerulus
• Glomerulus?filter
• Efferent arteriole
• ( ? vasoconstriction via
• ( ? angiotensin 2)
• Blood exiting
• glomerulus
• 
  

Microalbuminuria
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The elderly

• The 1 rule
• The process of senescence begins at ___?
• 1 decline in function per year in organ systems
  such as the liver
• Serum albumin in the elderly
• Decreased binding sites for drugsincreased
  bioavailability of drugs and drug toxicity

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The globulins

• The alpha 1 globulins
• High-density lipoproteinthe good guy
• HDLs clear excess cholesterol from the blood
  HDLs 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

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

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What else boosts HDLs?

• Exercise
• Exercise
• Ethanol

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Drink to boost HDLs

• 5 oz of wine of any colorThis amount?
• Guys, you can have 2 glasses
• How much of the hard stuff?
• 1 ounce for women
• 2 ounces for men
• How much beer?
• 12 ounces for women
• 24 ounces for men

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So, whats my motto?

• Run a mile, drink a beer, eat a bowl of beans and
  pop a Premarin
• Have a 5-ounce glass of chardonnay with a
  delicious salmon dinner with my Mom
• OR

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Increasing HDLs

• Decrease carbohydrate intake
• Say YES to drugs
• Niacin/Niaspan boosts HDL the mostup to 25
• Drugs the statin sisters are prescribed
  primarily to lower LDL cholesterol but can boost
  HDL by about 6 rosuvastatin boosts by 12)
  lovastatin (Mevacor), (simvastatin/Zocor,
  rosuvastatin/Crestor), atorvastatin (Lipitor),
  fluvastatin/Lescol, pravastatin/(Pravachol)
• Metformin (Glucophage) increases HDLs

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Alpha-2 globulins

• Transport proteinstransferrin (iron), Thyroid
  binding globulin (TBG), ceruloplasmin (copper)

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Beta globulinsthe bad guys

• LDLs (low density lipoproteins)directly deposit
  into the walls of the arteries via the process of
  oxidation
• The higher the LDLs, the greater the risk for
  atherosclerosis
• Particle size plays a role as well
• Small, dense LDLs vs. Large, loose LDLs

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LDL guidelines

• Guidelineswith CAD or a risk equivalent (stroke,
  peripheral arterial disease), the LDL should be
  70 mg/dL (2.0 mmol/L or even lower to 1.8 mmol/L)
• For the rest of us with other risk factors100
  mg/dL (lt2.85 mmol/L)
• Unless youre perfect--130 mg/dL (lt3.37 mmol/L)

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Risk factors for increased LDLs

• Diet high in trans and saturated fats
• Smoking
• High iron levels
• High insulin levels
• Couch potato
• Fat around the middle

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LDL reduction

• If youre boosting HDLs, youre reducing LDLs

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Say YES to statinsthe statin sisters

• The statins inhibit the enzyme in the liver
  responsible for producing LDL-cholesterol
• Since the liver works overtime at night, giving
  the statin drugs in the evening provides an even
  greater reduction in LDLs
• Statins decrease plaque formation, stabilize
  plaques, prevent plaque rupture

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VLDL (very low density lipoproteins)--triglyceride
s

• What increases TG? High fructose corn syrup,
  alcohol, pure sugar
• Are triglycerides bad for you? Yes, in
  excess--Increased risk of heart disease, high
  risk of PN and fatty liver in the diabetic
• Ideal is less than 150 mg/dL (1.70 mmol/L)
• Borderline high is 150-199 (1.70-2.25 mmol/L)

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Marine-based omega-3 fatty acids lower TG

• Prescription fish oil is Lovaza
• How about non-prescription fish oil?
• DHA and EPA should total 1000 mg/day for patients
  with high triglycerides so READ THE LABEL
• May see a Cardiologist prescribe even higher
  doses of fish oil depending on level of
  triglycerides

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Total cholesterolscreening purposes onlybest 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 (4.1-5.9) or hemoglobin A1C (4-6))
• 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)

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WBC and DIFFERENTIAL

• 5 types of mature WBCs and one immature WBC
  circulate in the cold, cruel world known as
  peripheral blood
• Normal range 5,000 to 10,000 (3500-12000) (5 to
  10 with a range of 3.5-12)

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The List

• Neutrophil (segs (57-63) of the total white
  count acute inflammation, acute necrosis, acute
  bacterial infection(1.51-7.07)
• Bands (0-4) (0.00-.51)precursor to the
  neutrophil
• 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)

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The granulocytes

• All of the cells with the last name phil are
  called granulocytes
• The neutrophils (segs) are most importantacute
  inflammation, acute necrosisphagocytic
• The eosinophils are increased in allergic
  responses and with parasitic infections
  (Carlotta)
• Basophilsallergies and anaphylaxis

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5 types of WBCs

• Neutrophils (seg)(phagocyte)-- 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)

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How do neutrophils grow up?

• Stem cells
• Myeloblast (BM)
• Promyeloctye (BM)
• Myelocyte (BM)
• Metamyelocyte (juvenile) (BM)
• Band neutrophil (BM and PB)
• Segmented neutrophil (BM and PB)

38
Neutrophils

• Neutrophils (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 necrosisMI, gangrene of the bowel, acute
  appendicitis

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Shift to the left

• During the time of acute need, the bone marrow is
  functioning overtimemassive production results
  in a partial loss of quality control concerning
  the level of maturity of the cells that are
  released into the peripheral blood
• WBC and diff will show an increased number of
  neutrophils and bands and maybe even a
  metamyelocyte (juvenile) or two
• shift toward immaturity
• Shift-to-the-leftincreased number of bands
• What is the usual number of bands? 0-4

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Clinical conditions with an increased WBC and
shift-to-the-left

• GABHS
• Pyelonephritis
• Acute appendicitis
• Bacterial meningitis

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Drugs and neutropenia

• Chemotherapy (all patients)ONCOLOGIC EMERG.
• 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

42
Neutrophils normal function

• Margination, pavementing, migration, engulfment
  and degranulation

Yum.
43
Prednisone and the neutrophil

• Inhibits migration and degranulation, hence its
  anti-inflammatory properties
• Prednisone also increases blood sugar high blood
  sugars can inhibit the function of neutrophils
• Diabetes Blood glucose greater than 180 mg/dL
  (9.99 mmol/L) inhibits neutrophil 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 segsis fever
  good for you? YES!

44
STRESS!

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

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InflammationC-reactive protein

• C-reactive protein -- lt 1 mg/dL or lt 10 mg/L
• 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
• hs-CRP (vascular inflammation) and coronary
  artery disease risk level
• low risk lt 1 mg/L Average 1-3 mg/L high risk
  gt 3 mg/L
• (Noncardiovascular causes should be considered if
  values are gt 10 mg/L)
• PROGNOSTIC INDICATOR (and screening for CV
  inflammationnext slide)

46
hs-CRPlow 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
• IL-6 and TNF-a 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
• YIKESso what should your waistline be?
• Ridker PM et al. N Engl J of Med 2000
  342836-43 Ridker PM et al. N Engl J of Med
  1997336973-9)

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What can reduce hs-CRP?

• Exercise
• Loss of abdominal fat
• Statins
• Pioglitazone (Actos)
• Aspirin
• Omega-3 fatty acids
• Nuts
• The Mediterranean diet is anti-inflammatory

48
Inflammationthe sed rate

• Sed raterate of the settling of RBCs in
  anticoagulated blood low sensitivity and
  specificity many factors can influence the sed
  rate used as a screening test and a prognostic
  indicator
• Newborn1-2mm/hr
• Neonates and children3-13 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 yearsthe maximum normal ESR at a
  given age is
• Males age in years/2
• Females age in years 10/2

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Monocyte/Macrophage

• Monocyte in blood, macrophage in tissue (Kupffer
  cell in liver, microglial cell in brain,
  osteoclast in bone, mesangial cell in kidney)
• 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

50
Chronic inflammation--TB

• Macrophages circling the pathogen is known as a
  granuloma
• Granulomatous diseases are chronic inflammatory
  diseases with osis as a last nametuberculosis,
  histoplasmosis, sarcoidosis, amyloidosis
• Macrophages secrete numerous cytokinesone is
  known as TNF-alpha (tumor necrosis factor-alpha)
  to contain the tubercle bacillis

51
Macrophages and TB

• red snappersthe tubercle bacillis
• If you have consumption,
• go up on the mountain
• The macrophage and vitamin D

52
Drugs that inhibit TNF-alpha

• TNF-alpha keeps TB in check
• It is also the culprit in certain diseases such
  as rheumatoid arthritis, Crohns disease,
  ankylosing spondylitis
• It is a potent inflammatory protein when released
  in large amounts
• Infliximab (Remicade), adalimumab (Humira),
  certolizumab (Cimzia), Golimumab (Simponi)
• Etanercept (Enbrel)--receptors

53
The macrophagethe link between inflammation and
immunity

• The macrophage is the antigen processing and
  presenting cell
• It engulfs the pathogen
• Chews it up
• Processes it and presents it to the helper T cell
  (T4 cell) of the immune system

54
Immunology in a nutshell
T4 cell
IL-2
ON
IL-1 release
TNF-a
CD4
IFN-G
CD4
macrophage With CD4 receptor
T4 or helper T cell
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Drugs and the immune system

• MacrophageMTX, Plaquenil
• HIV enters via CD4 and destroys
• IL-1 blocked by Prednisone
• TNF-alpha and drugs
• Interferon gamma boosts immune function
• T4 helper cellHIV enters via CD4 and destroys
• IL-2 is blocked by cyclosporin A

56
What else does IL-1 do?

• Increases temperature set point by increasing the
  production and release of prostaglandins in the
  hypothalamus

57
IL-1 release

• Increases serotonin release from
  brainstemvomiting
• Increases serotonin release from the
  duodenumnausea
• Duodenumthe organ of nausea

58
IL-1 release

• Increases melatonin production and makes you
  sleepy

59
IL-1 release

• Lowers pain thresholdeverything hurts
• Your hair hurts
• Your teeth hurt
• Your skin hurts
• Youre miserable

60
Cells of the immune system--lymphocytes
61
3 types of lymphocytes

• B lymphocytes (16)bone-marrow derived
• T lymphocytes (70)thymus-derived
• NK cells (14)Natural Killer cells (innate
  immunitypart of the first line of defense)

62
Cell-mediated immunityT cells

• Viruses
• Fungus
• Parasites
• Protozoa
• Cancer
• Transplants

63
T lymphocytes (thymus-derived)

• First responders to viral infections
• Release interferon alpha to inhibit viral
  attachment to surrounding cells
• T cells change their appearance and become
  atypical lymphocytes (reactive) or KILLER T
  cells
• One of the problems with the immune systemthe T
  cells can recognize, can respond, but cant KILL

64
Perfect examplethe herpes family

• HSV-1
• HSV-2
• VZV
• CMV
• EBV
• HHV-6, 7
• KSHV

65
B lymphocyte turns into plasma cell

• B lymphocytes are triggered by a foreign pathogen
• Turn into a mean, green antibody producing
  machine called a plasma cell
• Takes 7 to 21 days to produce antibodies with the
  initial response
• Memory response? Minutes to hours

66
B lymphocytes

• B cell---plasma cell---antibody production
  (immunoglobulins)--immunophoresis
• Y
• A uncontrolled proliferation (cancer) of the
  plasma cell is called multiple myelomaoverproduct
  ion of antibodies

67
Gamma globulins

• Immunophoresis
• IgM, IgG, IgA, IgD, IgE

-
68
Plasma cells produce antibodies

• IgMfirst antibody formed to an infection acute
  titersHSV-IgM (acute phase of infection)
• IgGsecond antibody formed to an infection lasts
  forever crosses placenta convalescent
  titersHSV-IgG (reactivation of earlier
  infection)

69
Plasma cells produce antibodies

• IgAbarrier antibody saliva, tears, urine,
  breast milk
• IgD--??

70
Immunoglobulin E

• IgEantibody of allergies
• Drills a hole in the
• mast cell
• releases primary granules
• full of histamine

71
What to do?

• Get rid of your pet?
• Dont sleep with the enemy?
• Give em a bath once a week?

72
RBCS AND ANEMIAS

• Barb Bancroft, RN, MSN, PNP
• www.barbbancroft.com
• barb_at_barbbancroft.com

73
What do you need to make happy healthy red blood
cells? Good Genes

• Bad genes and hemoglobinopathies

74
Hemoglobin ElectrophoresisHbA, HbS, HbF, HbAS,
HbSC, HbThal

• cathode
  anode -

Well in the gel
Electrical current running through gel
75
Healthy Kidneys

• Erythropoietin production and hypoxia
• rEPO has been available for nearly 2 decades
• Epoetin alfa and darbopoetin
• Renal failure and the use of recombinant
  erythropoietin
• Epo and the Black Market

76
Healthy thyroid--Hypothyroidismlow metabolic
rate

• Decreased metabolism decreases the production of
  red blood cells

77
Iron and RBCs

• How do we get iron?
• Foodespecially as children for vertical growth
• Foodnot so much in adults as we are not growing
  vertically and we usually get plenty of iron from
  our diet (only need 1 mg from diet of the 20 mg
  used per daythe other 19 mg is recycled through
  the senescence of old RBCs)
• Pregnancy -- need extra iron to grow a baby

78
How do we become deficient in iron?

• Bleedinganywhere women have 20 less blood than
  men, hence, lower iron stores and a greater risk
  of iron deficiency anemia also have periods
  premenopausally which increases risk of iron
  deficiency due to RBC depletion (and depends on
  type of period)
• BleedingALWAYS THINK GI, GI, GI

79
Iron absorption

• Fact You need a healthy duodenum to absorb iron
  and you need iron to grow vertically as a child
• Celiac disease primarily involves the duodenum
  consider a child with short stature with possible
  celiac disease
• Gastric by-pass surgery and duodenal exclusion
  surgeriesconsider iron deficiency

80
Iron

• Fact you need acid in the stomach to absorb iron
• Consider long-term acid suppression with proton
  pump inhibitors as a cause of iron deficiency
• Older individuals may have less gastric acid (not
  all, but some)

81
Tests for iron excess or deficiency

• Serum ferritin
• adults M 20-250 ng/mL or mcg/L
• F 10-120
• Iron overload gt 400 ng/mL in M and gt 200 ng/mL in
  females consider hemochromatosis
• Iron deficiency with levels lt 10 ng/mL (mcg/L)
• Total Iron Binding Capacity serum iron

82
B12 for RBC production

• Stored in the liver for 5-7 years
• 2,000 to 5,000 mcg is stored
• Use about 1 mcg per day for maintenance
• Takes 5-7 years of no B12 intake to deplete
  stores in the liver

83
Functions of B12

• Growth and differentiation of RBCs in the bone
  marrow
• Maintenance of CNS myelin, PNS myelin, and is a
  co-factor in the production of serotonin (happy)
• Not enough B12? Youre anemic, demented,
  depressed with a peripheral neuropathy

84
Notes on B12

• Foods high in B12? Animal protein, eggs, brewers
  yeast
• Glycoprotein in the stomach, intrinsic factor,
  binds to B12
• Tumbles into the small intestine where it is
  absorbed in the ileum
• Transported to liver for storage, bone marrow for
  RBC production nervous system

85
High risk groups(200-900 pg/mL)

• Over 55 years of age (problems with absorption)
• Lack of IF (intrinsic factor)autoimmune
  gastritis (pernicious anemia), gastrectomy
  patients
• No animal protein in dietvegetarians or Tea and
  Toasters
• Liver failure
• Lousy diet (alcoholics)no B12 in booze
• Malabsorption (Crohns disease, celiac disease,
  gastric by-pass surgery)
• Metformin PPIs

86
B12 deficiency

• The number one cause of nutritional DEMENTIA in
  North America
• B12 levels less than 200 pg/mL (however, this can
  vary)
• How can we replace B12? 4 waysthe 4 Ss
• how much?
• Can you overdose on B12?
• No, the one dreaded side effect of too much B12
  is

87
Folic acid and Dr. George Herbert

• 40 days and 40 nights
• Maintenance of healthy RBCs
• Dont forget the neural tube, young ladies!!
• Green leafys and citrus fruits, fortified cereals
  and breads

88
Drugs that block folic acid synthesis that are
taken longer than 40 days and 40 nights

• TMP/SFX (Bactrim, Septra)
• Rheumatrex (Methotrexate)
• Phenytoin (Dilantin)
• Oral contraceptives (new one with folic acid
  fortification is BeYaz)
• Supplement the first 3 with folic acid or any Ocs
  that dont contain folic acid

89
Differentiation and Maturation

• Stem cell (BM)
• Erythroblast (BM)(nucleated)
• Pronormoblast (BM) (nucleated)
• Normoblast (BM) (nucleated)
• Reticulocyte (BM and PB)(no nucleus)
• Erythrocyte (PB)(lives 109 days in blood)
• RBC count4.5 to 6 million
• (process takes 7-12 days to release a
  reticulocyte from bone marrow)

90
Nucleated RBCs in the peripheral bloodno, no
(blast cells)

• Has this patient had his/her spleen removed?
• The reticulocyte count0.5-1.5 of total RBC
  count takes 7-12 days to make and release a
  retic from the bone marrow
• Is this patient reticking?

91
Patient with a high retic count

• High retic count means that the bone marrow is
  making RBCs, but something is destroying them
  rapidlyeither in peripheral blood or bone marrow
  (hemolysis) and the bone marrow is working
  overtime to produce more
• 27-year-old African American female with anemia
• RBC3,000,000 (normal range 4.5-6 million)
• Retic count 35 (normal range 0.5-1.5)
• What should you think about?

92
Known as hemolytic anemias

• Sickle cell? Genetic hemoglobinopathy
• Thalassemia? (as above)
• G6PD deficiency?(as above)
• Autoimmune hemolytic anemia (lupus, drugs)
• Hemolytic uremic syndrome (drugs, E.coli)
• Coombs testwhat is it used for? If , it means
  an autoimmune process with antibodies against
  RBCs (drugs, lupus)

93
Low retic count

• Underproduction anemia
• Usually due to a deficiency of a nutrient
• Iron, B12, folic acid
• Chemotherapy

94
Some other numbers

• Hemoglobin
• adult females (11-15.5 g/dl) (110-155 g/L)
• males (13-17.3)(130-173 g/L)
• What is anemia defined as? Hemoglobin under 11
  g/dl (110 gL) for females and under 13 (130 g/L)
  for males

95
The size of the red blood cell also helps define
anemias

• Mean Cell Volume (MCV) 90 (83-97) fL
• microcytic anemia(RBCs are too small),
• Normocytic anemia (RBCs normal size)
• Macrocytic anemia (RBCs too large)

96
Microcytic anemia

• RBC 3,000,000 MCV65 (nl is 83-97)
• 9/10 with iron deficiency anemia
• Wheres the bleed? Female? Male? Exercise (too
  much pumping iron, marathon runners)? NSAIDS?
• occult blood in the stoolVERY importantGI, GI,
  GI
• Growing kid? Tea drinking? Long-term PPIs?
  Gastric acid suppression?

97
Microcytic anemia

• Thalassemia (do a hemoglobin electrophoresis)
• lead poisoning are two other causes of microcytic
  anemiaimmigrant house painter from Mexico? Kids
  and old houses? Toys from other countries?
• Lead levels? Basophilic stippling of RBCs

98
Macrocytic anemia

• RBC 3,000,000
• Defined as an MCV greater than 100 fL
• MCV between 100 and 120think booze
• MCV greater than 120think B12 or Folic acid
  deficiency
• Whos at risk?

99

• Chronic atrophic gastritispernicious anemia
  gastrectomy patients
• Chronic malabsorption (Crohns, gastric by-pass)
• Alcoholics
• Competition for B12 (tapeworms)
• Strict vegetarianism
• DrugsPPIs, metformin

100
Normocytic anemia

• RBCs 3,000,000
• MCV normal
• MCH normal
• The anemia of chronic diseaseCRF,
  hypothyroidism, chronic inflammation (TB), cancer
  (unless a bleed is involved)

101
Serum Enzymeslab test interpretation
102
Liver function tests

• Cellular integrity (SGOT, SGPT)also known as
  AST, ALT
• Bile formation and flow (bilirubin, GGT, alkaline
  phosphatase)
• Protein synthesis (albumin)

103
Hepatocellular enzymes

• AST (SGOT) is NON-specificin other words, it is
  found in many tissues and therefore not specific
  as a liver enzyme
• ALT (SGPT) is found almost exclusively in liver
  cells and is therefore highly specific for the
  liver
• If a healthy person demonstrates an elevated
  ALT, a thorough history is warranted with special
  questions such as hepatitis exposure, hepatotoxin
  exposure, and drug effects
• If enzymes are not terribly elevated (less than
  3x normal), recheck the enzyme levels in 2 weeks
  before doing a multi-million dollar work-up

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Normal AST/ALT ratio 1

• AST 8-20 U/L (0.43-1.28 µKat/Ladult males 11-26
  U/L (0.19-0.44 µKat/Ladult females)
• ALT 10-40 U/L (0.17-0.68 µKat/Ladult males 7-35
  U/L (0.12-0.60)
• What is the ratio? Should be 1
• If greater than one consider ETOH
• AST is especially sensitive to alcohol
• If alcohol damages liver cells, the AST will
  increase higher than the ALT
• Ratio in alcohol induced hepatitis is usually 31
  to 81

105
AST/ALT ratio

• If less than 1 consider drugs, viruses,
  autoimmune hepatitis, hemochromatosis, Wilsons
  disease, alpha-1 antitrypsin deficiency,
  nonalcoholic fatty liver disease, fast food
  fanatics
• Always check the TSHmay see mild increase in
  liver enzymes with hypothyroidism

106
3 most common causes of unexplained ALT elevations

• Persons with unexplained ALT elevations,
  documented to be elevated for at least 6 months
• chronic hepatitis C
• alcoholic liver disease, and
• nonalcoholic fatty liver disease (NAFLD) or NASH
  (nonalcoholic steatohepatitis)

107
NASH

• NASH (nonalcoholic steatohepatitis) is defined as
  steatosis significant liver inflammation is
  characterized by presence of neutrophil (segs)
  infiltrates leading to inflammation, fibrosis and
  10-20 progress to cirrhosis
• Elevated liver enzymes in 90 of the patients
  AST/ALT is less than 1, in contrast to alcoholic
  steatohepatitis in which the ratio is above
  2.0-2.5
• Usually asymptomatic or nonspecific sx such as
  fatigue and RUQ discomfort

108
Causes of non-alcoholic fatty liver disease

• Obesity
• Diabetes
• The above two have traditionally been the only
  causes of NAFLD, but there are more
• Males greater than females
• Drugsprednisone, MTX, synthetic estrogens,
  amiodarone (Cordarone, Pacerone), tamoxifen,
  nifedipine, and diltiazem

109
Other causes of elevated liver enzymes

• Chemicals (cleaning chemicals such as CCl4 ),
  vinyl chloride
• Dont combine cleaning chemicals with alcohol!
• Vitamin A toxicity
• Herbal productsYerba tea, germander, skull cap,
  mistletoe (Iscador)

110
Drug-induced liver injury (DILI)

• Acetaminophen (over 300 OTC products combined
  with opiatescets) booze and no food
• Anabolic steroids
• Statins (not so bad on liver, more side effects
  w/ muscle aches and pains)
• NSAIDS especially diclofenac (Voltaren)
• Amiodarone
• Rheumatrex
• Valproic acid (Depakote)
• Isoniazid (INH)
• Azathioprine (Imuran)

111
Viral causes of elevated liver enzymes.

• Hepatitis Arisk factors
• fecal-oral transmission
• Salad bars can be particularly dangerous
• The scallions at Chi-Chis in Pittsburgh (October
  2003)

112
Hepatitis Brisk factors

• Vertical transmission (90 of cases)
• Sexually transmitted
• IV drug use
• Day careminor cuts
• Blood transfusionsrisk is negligible in North
  America
• Very low risk of blood transfusion related --9
  cases in 3.7 million donations (N Enlg J Med 2011
  Jan 20 364236

113
Hepatitis C virushigh risk groups

• IV drug user (even 1 time experimental drug
  use)(54 of total cases)
• Needle stick injury (10)
• High risk conditions associated with high
  prevalence of HCVHIV (HCV is more aggressive in
  the context of HIV co-infection)(25 of people
  living with HIV are co-infected with hepatitis C)

114
Hepatitis C risk factors

• Blood transfusions prior to July1992 or organ
  transplant recipients (the risk of blood
  transfusion HCV in the U.S. is close to zero
  risk of acquiring HCV by needle stick is about 6x
  higher than that for HIV (1.8 vs. 0.3)
• Persons who have ever received hemodialysis
• Hemophiliacs who received clotting factor
  concentrates prior to 1987
• Children born to HCV-infected moms (screen at age
  1 or older)(6 transmission rate)

115
Hepatitis C high risk factors

• HCW after a mucosal exposure to HCV-positive
  blood (1.5 of total cases)
• Current sexual partners of HCV-infected persons
  (prevalence is low, but a negative test provides
  reassurance)

116
Hepatitis C virussecondary risk factors

• Sexual transmission with multiple partnerswhat
  does multiple mean?
• Intranasal cocaine use
• Tattoos (prison applied?)
• Piercings
• Receipt of injection in a developing world
• Endoscopy clinics in Nevada (reuse of needles and
  syringes) other outbreaks in U.S. due to reuse
  of medical devices without proper sterilization)
• (Parkinson E. What now? Responding to relapse in
  Hepatitis C. Advance for NPs 2007
  (December)49-51)

117
Alkaline Phosphatase (ALP)

• Think Biliary and Bone
• Any disturbance in the synthesis, secretion, or
  excretion of bile leads to the accumulation of
  bile acids in the liver
• This in turn increases the synthesis of ALP
• Sensitive indicator of cholestasis (gall
  bladderpostmenopausal women on HT are at
  increased risk) also Fair, fat, forty, fertile,
  female and flatulent
• Infiltrative processes such as liver mets

118
Alkaline Phosphatase (ALP)

• Dont forget ALP is found in bone
• Osteoblasts
• Increased with growth spurts1st year and
  adolescence
• Pagets disease
• Osteosarcoma
• Metastatic disease to bonebreast, prostate,
  melanoma

119
Pancreatic enzymes

• Amylase and lipase
• Amylase also found in the parotid gland (mumps)
• With pancreatitis, amylase rises fast and high
  (up to 60,000) in the first 12 hours
• What are the 2 major causes of acute
  pancreatitis? Booze and gallstones

120
Creatine Kinase--CK

• High-energy tissues
• Skeletal muscle (98 CK-3, CK-MM 2 is CK-MB)
• Cardiac muscle (40 CK-2, CK-MB 60 CK-MM)
• Brain (CK-1, CK-BB)(also large intestine, CK-BB)

121
LDHLDH1,2,3,4,5

• Found in practically every cell
• The most common enzyme elevated on routine tests
• Usually an isolated enzyme elevation and not
  indicative of a problem
• LDH1 is from cardiac muscle
• LDH2 is from serum
• LDH5 is the most common elevationprobably
  skeletal muscle damage

122
Troponin T

• Structural protein, not serum enzyme
• Greater than 0.03 mcg/L is the 10 CV cutpoint
• Cardiac necrosis
• More cardiac specific than CK-MB, remains
  elevated for 3-14 days
• Advantage for delayed diagnosis
• Rises in 3-12 hours, peaks at 24, down in 3-14
  days (if not elevated 6 to 9 hours after chest
  pain onsetACS not likely)

123
Thanks.

• Barb Bancroft, RN, MSN, PNP
• www.barbbancroft.com
• BBancr9271_at_aol.com