INTERPRETATION OF LAB TESTS
Barb Bancroft, RN, MSN
www.barbbancroft.com
BBancr9271@aol.com
Rule number one …
• Know your own lab’s normal values
• Various methods of testing and various
“normal ranges”…
Serum protein electrophoresis
• List the plasma proteins
1) albumin
2) globulins
3) fibrinogen
• Is there a difference between serum proteins
and plasma proteins?
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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
What else?
• Endogenous estrogen?
• Estrogen excess increases fibrinogen
• Combined oral contraceptives? The “old days”
vs. today’s COCs…
• HT? (hormone therapy)
• Dose dependent…age dependent…
• Aging and fibrinogen—increases by 1% per
year after age 30
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…
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 lungs—Pulmonary embolism at 7:30 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
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
Serum Protein Electrophoresis—based on molecular
weight and overall charge (positive or negative)
• +
-
Well in the gel
Electrical current running through gel
Serum electrophoresis
albumin
globulins
α1
α2
β
Γ
Albumin
• Functions—holds 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 disease—decreased synthesis due to liver
disease or due to an OLD liver…(1% rule)
• Or leaky kidneys…
Patient with ascites?
• SAAG—serum ascites/albumin gradient;
• SAAG=albuminserum / albuminascites
• ratio greater than 1.1 is 97% predictive of
portal hypertension as the cause of ascites
• SAAG less than 1.1 is nonportal
hypertension—nephrotic syndrome, infection
(TB, fungal, CMV), pancreatic ascites, ovarian
cancer, peritoneal carcinomatosis
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
“Prils”—The ACE inhibitors
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Captopril (Capoten)
Enalapril (Vasotec)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moxepril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
Etc…
“Angie” and the healthy kidney…
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Afferent arteriole
(vasodilated via
(prostaglandins)
Blood entering
glomerulus
Glomerulus→filter
Efferent arteriole
(vasoconstricted via
(angiotensin 2)
Blood exiting
glomerulus
PG
filter
AT2
Toilet
“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**
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 drugs—increased
bioavailability of drugs and drug toxicity
The globulins…
The alpha 1 globulins—
1) High-density lipoprotein—the good guy
2) 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
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
What else boosts HDLs?
• Exercise
• Exercise
• Ethanol
Drink to boost HDLs…
• 5 oz of wine of any color—This 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
So, what’s 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…
Increasing HDLs
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Decrease carbohydrate intake
Say YES to drugs…
Niacin/Niaspan boosts HDL the most—up 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
Alpha-2 globulins
• Transport proteins—transferrin (iron), Thyroid
binding globulin (TBG), ceruloplasmin (copper)
Beta globulins—the 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
LDL guidelines
• Guidelines—with 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 factors—100
mg/dL (<2.85 mmol/L)
• Unless you’re perfect…--130 mg/dL (<3.37
mmol/L)
Risk factors for increased LDLs
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Diet high in trans and saturated fats
Smoking
High iron levels
High insulin levels
Couch potato
Fat around the middle
LDL reduction
• If you’re boosting HDLs, you’re reducing LDLs…
Say YES to statins—the “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
VLDL (very low density lipoproteins)-triglycerides
• 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)
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
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 (4.15.9) 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)
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) (5
to 10 with a range of 3.5-12)
The List…
• Neutrophil (segs (57-63%) of the total white count; acute
inflammation, acute necrosis, acute bacterial infection(1.517.07)
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)
The granulocytes…
• All of the cells with the last name “phil” are
called granulocytes
• The neutrophils (segs) are most important—
acute inflammation, acute necrosis—
phagocytic
• The eosinophils are increased in allergic
responses and with parasitic infections
(Carlotta)
• Basophils—allergies and anaphylaxis
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)
How do neutrophils grow up?
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Stem cells
Myeloblast (BM)
Promyeloctye (BM)
Myelocyte (BM)
Metamyelocyte (juvenile) (BM)
Band neutrophil (BM and PB)
Segmented neutrophil (BM and PB)
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 necrosis—MI, gangrene of the bowel,
acute appendicitis
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 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-left—increased number of bands
• What is the usual number of bands? 0-4%
Clinical conditions with an increased WBC
and “shift-to-the-left”
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GABHS
Pyelonephritis
Acute appendicitis
Bacterial meningitis
Drugs and neutropenia
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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
Neutrophils …normal function
• Margination, pavementing, migration,
engulfment and degranulation
Yum.
Prednisone and the neutrophil
• Inhibits migration and degranulation, hence its antiinflammatory 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 segs—is fever good for you?
YES!
STRESS!
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Stress and the WBC
Screaming kids
24-hours post-op
Last trimester of pregnancy
No bands
Inflammation—C-reactive protein
• C-reactive protein -- < 1 mg/dL or < 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 < 1 mg/L; Average 1-3 mg/L; high risk > 3 mg/L
(Noncardiovascular causes should be considered if values are >
10 mg/L)
PROGNOSTIC INDICATOR (and screening for CV inflammation—
next slide)
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
• 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)
What can reduce hs-CRP?
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Exercise
Loss of abdominal fat
Statins
Pioglitazone (Actos)
Aspirin
Omega-3 fatty acids
Nuts
The Mediterranean diet is anti-inflammatory
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; used as a screening test and a prognostic indicator
• 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
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
Chronic inflammation--TB
• Macrophages circling the “pathogen” is known as a
granuloma
• Granulomatous diseases are chronic inflammatory
diseases with “osis” as a last name…tuberculosis,
histoplasmosis, sarcoidosis, amyloidosis
• Macrophages secrete numerous cytokines—one is
known as TNF-alpha (tumor necrosis factor-alpha) to
contain the tubercle bacillis…
Macrophages and TB
• “red snappers”—the tubercle bacillis
• “If you have consumption,
go up on the mountain…”
• The macrophage and vitamin D
Drugs that inhibit TNF-alpha
• TNF-alpha keeps TB in check
• It is also the “culprit” in certain diseases such as
rheumatoid arthritis, Crohn’s 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
The macrophage—the 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
Immunology in a nutshell…
CD4
IL-1 release
TNF-a
IFN-Γ
macrophage
With CD4 receptor
IL-2
T4 cell
CD4
T4 or helper T cell
“ON”
Drugs and the immune system
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Macrophage—MTX, Plaquenil
HIV enters via CD4 and destroys
IL-1 blocked by Prednisone
TNF-alpha and drugs
Interferon gamma boosts immune function
T4 helper cell—HIV enters via CD4 and
destroys
• IL-2 is blocked by cyclosporin A
What else does IL-1 do?
• Increases temperature set point by increasing
the production and release of prostaglandins
in the hypothalamus
IL-1 release…
• Increases serotonin release from brainstem—
vomiting
• Increases serotonin release from the
duodenum—nausea
• Duodenum—the organ of nausea
IL-1 release…
• Increases melatonin production and makes
you sleepy
IL-1 release…
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Lowers pain threshold—everything hurts
Your hair hurts
Your teeth hurt
Your skin hurts
You’re miserable…
Cells of the immune system-lymphocytes
3 types of lymphocytes
• B lymphocytes (16%)—bone-marrow derived
• T lymphocytes (70%)—thymus-derived
• NK cells (14%)—Natural Killer cells (innate
immunity—part of the first line of defense)
Cell-mediated immunity—T cells
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Viruses
Fungus’
Parasites
Protozoa
Cancer
Transplants
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 system…the T
cells can recognize, can respond, but can’t KILL
Perfect example—the “herpes family”
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HSV-1
HSV-2
VZV
CMV
EBV
HHV-6, 7
KSHV
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
B lymphocytes
• B cell---plasma cell---antibody production
(immunoglobulins)--immunophoresis
Y
A uncontrolled proliferation (cancer) of the plasma
cell is called multiple myeloma—overproduction of
antibodies
Gamma globulins
• Immunophoresis
• IgM, IgG, IgA, IgD, IgE
+
-
Plasma cells produce antibodies…
• IgM—first antibody formed to an infection
“acute titers”—HSV-IgM (acute phase of
infection)
• IgG—second antibody formed to an infection;
lasts “forever”; crosses placenta;
“convalescent titers”—HSV-IgG (reactivation
of earlier infection)
Plasma cells produce antibodies…
• IgA—barrier antibody; saliva, tears, urine,
breast milk
• IgD--??
Immunoglobulin E
• IgE—antibody of allergies
• Drills a hole in the
mast cell—
releases primary granules
full of histamine
What to do?
• Get rid of your pet?
• Don’t sleep with the enemy?
• Give ‘em a bath once a week?
RBC’S AND ANEMIAS
Barb Bancroft, RN, MSN, PNP
www.barbbancroft.com
barb@barbbancroft.com
What do you need to make happy healthy red
blood cells? Good Genes
• Bad genes and hemoglobinopathies
Hemoglobin Electrophoresis—HbA,
HbS, HbF, HbAS, HbSC, HbThal…
+ cathode
anode -
Well in the gel
Electrical current running through gel
Healthy Kidneys…
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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
Healthy thyroid-Hypothyroidism…low metabolic rate
• Decreased metabolism decreases the
production of red blood cells
Iron and RBCs
• How do we get iron?
• Food—especially as children for vertical growth
• Food—not 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
day—the other 19 mg is recycled through the
senescence of old RBCs)
• Pregnancy -- need extra iron to grow a baby
How do we become deficient in
iron?
• Bleeding—anywhere; 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)
• Bleeding—ALWAYS THINK GI, GI, GI
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 surgeries—consider iron deficiency
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)
Tests for iron excess or deficiency
• Serum ferritin
adults –M = 20-250 ng/mL or mcg/L
F = 10-120
Iron overload > 400 ng/mL in M and > 200
ng/mL in females; consider hemochromatosis
Iron deficiency with levels < 10 ng/mL (mcg/L)
• Total Iron Binding Capacity; serum iron
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
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? You’re anemic, demented,
depressed with a peripheral neuropathy
Notes on B12
• Foods high in B12? Animal protein, eggs,
brewer’s 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
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 diet—vegetarians or Tea and
Toasters
• Liver failure
• Lousy diet (alcoholics)—no B12 in booze
• Malabsorption (Crohn’s disease, celiac disease, gastric
by-pass surgery)
• Metformin; PPIs
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 ways…the 4 S’s
• how much?
• Can you overdose on B12?
• No, the one dreaded side effect of too much B12 is:
Folic acid and Dr. George Herbert
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40 days and 40 nights
Maintenance of healthy RBCs
Don’t forget the neural tube, young ladies!!
Green leafys and citrus fruits, fortified cereals and
breads
Drugs that block folic acid synthesis that are
taken longer than 40 days and 40 nights…
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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 don’t contain folic acid
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 count—4.5 to 6 million
(process takes 7-12 days to release a reticulocyte
from bone marrow)
Nucleated RBCs in the peripheral blood—no, no
(blast cells)
• Has this patient had his/her spleen removed?
• The reticulocyte count…0.5-1.5% of total RBC
count; takes 7-12 days to make and release a
“retic” from the bone marrow
• Is this patient “reticking”?
Patient with a high retic count
• High retic count means that the bone marrow is
making RBCs, but something is destroying them
rapidly—either 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
• RBC=3,000,000 (normal range = 4.5-6 million)
• Retic count 35% (normal range = 0.5-1.5%)
• What should you think about?
Known as hemolytic anemias
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Sickle cell? Genetic hemoglobinopathy
Thalassemia? (as above)
G6PD deficiency?(as above)
Autoimmune hemolytic anemia (lupus, drugs)
Hemolytic uremic syndrome (drugs, E.coli)
Coomb’s test—what is it used for? If +, it
means an autoimmune process with
antibodies against RBCs (drugs, lupus)
Low retic count
• Underproduction anemia
• Usually due to a deficiency of a nutrient
• Iron, B12, folic acid
• Chemotherapy
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
The size of the red blood cell also
helps define anemias
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Mean Cell Volume (MCV) – 90 (83-97) fL
microcytic anemia(RBCs are too small),
Normocytic anemia (RBCs normal size)
Macrocytic anemia (RBCs too large)
Microcytic anemia
• RBC 3,000,000; MCV=65 (nl is 83-97)
• 9/10 with iron deficiency anemia
• Where’s the bleed? Female? Male? Exercise
(too much pumping iron, marathon runners)?
NSAIDS?
• occult blood in the stool—VERY important—
GI, GI, GI
• Growing kid? Tea drinking? Long-term PPIs?
Gastric acid suppression?
Microcytic anemia
• Thalassemia (do a hemoglobin
electrophoresis)
• lead poisoning are two other causes of
microcytic anemia—immigrant house painter
from Mexico? Kids and old houses? Toys from
other countries?
• Lead levels? Basophilic stippling of RBCs
Macrocytic anemia
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RBC 3,000,000
Defined as an MCV greater than 100 fL
MCV between 100 and 120—think booze
MCV greater than 120—think B12 or Folic acid
deficiency
• Who’s at risk?
• Chronic atrophic gastritis—pernicious anemia;
gastrectomy patients
• Chronic malabsorption (Crohn’s, gastric bypass)
• Alcoholics
• Competition for B12 (tapeworms)
• Strict vegetarianism
• Drugs—PPIs, metformin
Normocytic anemia
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RBCs 3,000,000
MCV normal
MCH normal
The anemia of chronic disease—CRF,
hypothyroidism, chronic inflammation (TB),
cancer (unless a bleed is involved)
Serum Enzymes…lab test
interpretation
Liver function tests
• Cellular integrity (SGOT, SGPT)—also known as
AST, ALT
• Bile formation and flow (bilirubin, GGT,
alkaline phosphatase)
• Protein synthesis (albumin)
Hepatocellular enzymes
• AST (SGOT) is NON-specific…in 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 multimillion dollar work-up
Normal AST/ALT ratio ~ 1
• AST 8-20 U/L (0.43-1.28 μKat/L—adult males; 11-26 U/L (0.190.44 μKat/L—adult females)
• ALT 10-40 U/L (0.17-0.68 μKat/L—adult males; 7-35 U/L (0.120.60)
• 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 3:1 to 8:1
AST/ALT ratio
• If less than 1 consider drugs, viruses,
autoimmune hepatitis, hemochromatosis,
Wilson’s disease, alpha-1 antitrypsin
deficiency, nonalcoholic fatty liver disease, fast
food fanatics
• Always check the TSH—may see mild increase
in liver enzymes with hypothyroidism
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)
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 2.02.5
• Usually asymptomatic or nonspecific sx such
as fatigue and RUQ discomfort
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
• Drugs—prednisone, MTX, synthetic estrogens,
amiodarone (Cordarone, Pacerone), tamoxifen,
nifedipine, and diltiazem
Other causes of elevated liver enzymes
• Chemicals (cleaning chemicals such as CCl4 ),
vinyl chloride
• Don’t combine cleaning chemicals with
alcohol!
• Vitamin A toxicity
• Herbal products—Yerba tea, germander, skull
cap, mistletoe (Iscador)
Drug-induced liver injury (DILI)
• Acetaminophen (over 300 OTC products + combined with
opiates…”cets”) + 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)
Viral causes of elevated liver
enzymes….
• Hepatitis A—risk factors
fecal-oral transmission
Salad bars can be particularly dangerous
The scallions at Chi-Chi’s in Pittsburgh (October
2003)
Hepatitis B—risk factors
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•
•
•
•
Vertical transmission (90% of cases)
Sexually transmitted
IV drug use
Day care—minor cuts
Blood transfusions—risk 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; 364:236
Hepatitis C virus—high 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 HCV—HIV (HCV is more
aggressive in the context of HIV coinfection)(25% of people living with HIV are
co-infected with hepatitis C)
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)
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)
Hepatitis C virus—secondary risk factors
• Sexual transmission with multiple partners—what 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)
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 bladder—
postmenopausal women on HT are at increased risk);
also Fair, fat, forty, fertile, female and flatulent
• Infiltrative processes such as liver mets
Alkaline Phosphatase (ALP)
• Don’t forget ALP is found in bone
• Osteoblasts
• Increased with growth spurts—1st year and
adolescence
• Pagets disease
• Osteosarcoma
• Metastatic disease to bone—breast, prostate,
melanoma
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
Creatine Kinase--CK
• High-energy tissues
• Skeletal muscle (98% CK-3, CK-MM; 2% is CKMB)
• Cardiac muscle (40% CK-2, CK-MB; 60% CKMM)
• Brain (CK-1, CK-BB)(also large intestine, CK-BB)
LDH—LDH1,2,3,4,5
• 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 elevation—
probably skeletal muscle damage
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 onset—ACS not likely)
Thanks.
• Barb Bancroft, RN,
MSN, PNP
• www.barbbancroft.com
• BBancr9271@aol.com