Diagnostic Tests

Myocardial Infarction Cardiac Panel

Total CK (CPK) - due to damage of brain/lungs (BB), heart (MB), skeletal muscle (MM)
- not specific for MI

CK-MB - cardiac specific

- not necessarily for MI, can be elevated due to other cardiac diseases i.e.
CPR, cardioversion, Cocaine abuse, blunt chest trauma, defib.,
cardiac/ noncardiac surgical procedures, angina
- rise: 4-6 hrs; fall: 36-48 hrs; persists for 10-14 days

Troponin-I - cardiac specific

- preferred marker for acute MI (AMI)
- rise: 2-3 hrs; peak: 12 hrs; persists for 10 days
- rises before CK-MB but won’t rise in angina

Myoglobin - cardiac specific

- highly sensitive for MI
- rise: 2-3 hrs; peak: 8-12 hrs; persists <24 hrs
- affected by renal function and muscle injury
- often rises before troponin-I

Renal
BUN (blood urea nitrogen) - indirectly measures kidney function
- dependent on production of urea from liver so, if liver is
damaged, not a helpful value
- low levels uncommon
- can rise due to dehydration and other factors

Creatinine - more specific than BUN

- indirectly measures kidney function
- rises due to kidney damage, infection, necrosis, obstruction,
decreased blood flow
- low levels uncommon

BUN/Creatinine Ratio - helps determine pre-renal or renal cause

- pre-renal >20:1
- renal 10-15:1
- post-renal evolves

Pancreatitis
Amylase - SENSITIVE test
- rise is 4-6x normal value within 12-72 hrs
- remains elevated until treated
- dependent on pancreatic activity; significant damage will give decreased levels

Lipase - SPECIFIC test

- rise is 5-10x normal values within 24-48 hrs
- returns to normal after 7-10 days
- dependent on pancreatic activity
CBC (complete blood count)
RBC count - most abundant CBC component
- carries Hgb to carry oxygen
- 120 day lifespan and destroyed by spleen

MCV - measures size (normocytic, microcytic, macrocytic)

MCH - measures weight of Hgb (resembles MCV)

MCHC - measures hgb content (normochromic, hypochromic, hyperchromic)

RDW - measures size (normocytic, microcytic, macrocytic)

Hemoglobin - measures total Hgb in blood & reflects number of RBCs

- increased due to erythrocytosis
- decreased due to anemia

Hematocrit - measures percentage of total blood volume made up by the RBCs

- usually 3x’s Hgb concentration

WBC count - leukopenia due to lymphocytes, granulocytes or both

- decreased production due to leukemia, chemotherapy, or NSAIDs
- increased removal due to RA, infection, or destruction of spleen

Neutrophils - bands (immature) or segs/PMNs (mature)

- increase in neutrophils & bands (left shift) points to infection
- occurs due to clozapine, thyroid meds, immune disorder, or post-infection like HIV
- ANC= WBC x (PMNs+bands %)/ 100
- value <1000 at risk for infection; <500 at risk for infection from normal flora

Lymphocytes - doesn’t differentiate between B & T cells

- increases due to viral infection or neoplasia
- decreases due to HIV or immune suppression
- atypical lymphocytes common in 2nd-3rd week of mono. infection

Monocytes - increases due to infection

- decreases due to HIV, RA, bone marrow
- grayish-blue cytoplasm & folded nucleus

Eosinophils - increased due to allergy, parasitic infection

- decreased due to stress, bone marrow
- orange granules, bi-lobed nucleus

Basophils - not commonly elevated

- serious problem if there is elevation

Platelets - small, anucleated, irregularly shaped cells

- lifespan: 7-10 days
- a third resides in spleen so spleen problems will affect platelet number
- involved in coagulation so # affected due to thrombocytopenia & thrombocytosis
- S/S include petechiae, purpura, ecchymosis, & bleeding if abnormal
Basic Metabolic Panel
Na+ Normal regulation: more in ECF >ICF, reflects hydration status
Purpose: need Na+ to maintain BP, muscle and nerve function
ADH: responds to Na , retains H2O and induces thirst
+
Aldosterone: responds to Na+, retains Na+ and excretes K+
Hypernatremia: dehydration due to Na > H20
1. decreased intake of H20: exercise, mentally impaired, infants/elders
2. increased excretion of H20: diarrhea, hyperaldosteronism, osmotic diuresis

Hyponatremia: Na < H2O

1. too much H20: overhydration, SIADH, Addison’s disease (aldosterone deficiency)
2. too little Na: low Na+ diets, vomiting, GI suctioning, burns, diuretics

K+ Normal regulation: more in ICF > ECF, small changes in serum K VERY significant
Purpose: monitor diuretics (can cause excretion of K+), renal disease (increase in K+)
Hyperkalemia: hemolysis, excessive intake, kidney failure, metabolic acidosis, diabetic ketoacidosis, Addison’s disease

Hypokalemia: diuretics, diet/IV, vomiting/diarrhea/sweating, metabolic alkalosis, dialysis, hyperaldosteronism

Cl- Normal regulation: ECF >ICF, follows changes in Na+, buffer in acid-base balance
Purpose: maintain electrical neutrality, Anion gap: Na + - (Cl- + HCO3-)
Hyperchloremia: dehydration, increased intake of NaCl, kidney dysfunction

Hypochloremia: overhydration, CHF, SIADH, vomiting, GI suctioning, Addison’s disease

CO2 Normal regulation: measure of total HCO3- + dissolved CO2

Purpose: evaluate acid-base balance, anion gap, regulated by kidneys

Increased CO2: metabolic alkalosis due to diarrhea, vomiting, emphysema

Decreased CO2: metabolic acidosis, renal failure due to drug overdose, diabetic ketoacidosis
BUN Normal regulation: liver produces urea which is broken down into nitrogen, relies on functional liver to indirectly evaluate
kidney function (filters BUN)

High BUN (AZOTEMIA):

Pre-renal cause: dehydration, massive bleed [not filtering BUN]
Renal cause: glomeruli damage, renal vessel damage [BUN reabs. > BUN excretion]
Post-renal cause: obstruction- prostate, hydroephrosis (obst. in ureters) [BUN reabs.]

Low BUN: not worrisome

Common causes: poor nutrition, pregnancy, overhydration/SIADH
Less common cause: severe liver disease
Creatinine Normal regulation: waste product of muscle metabolism, completely excreted so better reflection of kidney function,
variable from patient to patient due to muscle mass

High Creatinine:
Pre-renal cause: reduced renal flow- shock, dehydration, athersclerosis
Renal cause: glomerulonephritis, pyelonephritis
Post-renal cause: obstruction

Low Creatinine: decreased muscle mass especially in older adults

BUN/Creat only applicable if BUN/Creatinine are high
Ratio Pre-renal: >20:1, Intrarenal: <10-15:1, Post-renal: evolves- initially high then drops
Glucose Purpose: fasting glucose (8hrs w/out food or drink) to detect hyper or hypoglycemia

Hyperglycemia: DM (FS > 126 mg/dL), hyperthyroidism, stress, post-surgery, steroids, liver disease

Hypoglycemia: too much insulin, liver disease, rx meds (ASA), insulinomas, galactosemia, hypopituitary disease, adrenal
insuffiency
Calcium Purpose: bone structure, nerve impulses, muscle contractions, parathyroid function, malignancies
Hypercalcemia: hyperparathyroidism, malignancies (bone, cervical, prostate), ectopic PTH production, vitamin D
intoxication

Hypocalcemia: hypoalbuminemia, hypoparathyroidism, vitamin D deficiency, malabsorption syndromes, renal failure

Comprehensive Metabolic Panel =Basic Metabolic Panel + Liver Function Panel

Liver Function Panel

Asparate Aminotransferase (AST)
- enzyme released when cells are lysed, NOT SPECIFIC to liver
- elevated 8 hrs. after cell injury
- peak 24-36 hrs
- if resolved, return to normal 3-7 d; if not resolved, will stay elevated
- look for significant elevation
- 20x normal= acute viral hepatitis, drug overdose
- 10x normal= gallstones
- cirrhosis- wide variation

Alanine Aminotransferase (ALT) - SPECIFIC to liver disease

- elevation remains for longer duration
- look for significant increase

AST/ALT ratio - only applicable if AST & ALT values are abnormal
>2 = alcoholic cirrhosis
1 – 2x = cirrhosis & chronic hepatitis
<1 = acute hepatitis, mono
If AST >10x = ratio not accurate
- things that interfere with results:
- caffeine (ALT)
- muscle disease (AST & ALT), E-mycin, ASA (AST)

Alkaline Phosphatase (ALP) - NOT SPECIFIC, from liver or bone

- elevation due to biliary obstruction, [cirrhosis], metastatic liver tumor,
new bone growth, bone destruction
- variation w/ age: kid>adult; older adult> younger adult

GGT - enzyme in hepatic & biliary cells

- SENSITIVE, not specific
- elevation due to biliary disorders, alcoholism

Bilirubin TOTAL: catabolic product of heme metabolism

both direct & indirect bilirubin
elevation causes jaundice
DIRECT: conjugated in liver, gives stool brown color
elevation due to duct obstruction, gallstones, pancreatitis
INDIRECT: unconjugated, going from spleen to liver
elevated due to hemolytic disease of newborn, cirrhosis, transfusion

Albumin - contributes to osmotic pressure, transports Ca2+

- low levels due to glomerular problems, chronic liver disease
- high levels due to dehydration

Total Protein - combination of all proteins in serum (60% albumin)

- contributes to osmotic pressure in vessels
- low levels due to malnutrition, burns, post-surgery, pregnancy
- high levels due to dehydration, prolonged tourniquet use
Labs not included in CMP
Lactate Dehydrogenase (LDH)
Magnesium
HbA1C
- NOT SPECIFIC or SENSITIVE for liver disease
- for liver, look at the following isoenzymes:
LDH2= reticuloendothelial system
LDH5= liver and striated muscle
- elevation can also be due to MI, hemolysis
- total level of LDH not that helpful
- most is intracellular in bone & muscle
- abnormality linked to K+ and Ca2+
- check levels especially when having trouble correcting K+ levels
Increased Mg+: chronic renal disease, oral/IV infusion (laxatives/antacids)
Decreased Mg+: malnourished, renal or GI losses (diarrhea, suctioning)
cause of unexplained: cardiac arrhythmias, neuromusc. disorders
- reflects average glucose levels over extended period of time (120 days)
- measures glycosylation of RBCs which is irreversible
- helpful in monitoring blood sugar in patients with DM
Systemic Inflammation
C- Reactive Protein (CRP)
Erythrocyte Sedimentation
Rate (ESR)
- acute phase reactant
- no known normal level, need to do a comparison with previous value
- used to follow disease process/monitor improvement
- elevation can detect inflammation but there are many interfering factors
-i.e. steroids, ASA, EtOH (), smoking, estrogen, HTN ()
- quick changes: rise in 4-6 hrs, peak in 48 hrs
- cannot make DDx by this test alone
- not an acute phase reactant, indirect measure of inflammation
- rate at which RBCs settle in a tube
- used to follow disease process/ monitor improvement
- rises and falls more slowly than CRP, less reliable compared to CRP
- high ESR value = faster settling = high fibrinogen = indicates inflammation
- primarily used to detect temporal arteritis, polymalgia rheumatica
- many interfering factors: pregnancy, menstruation (), ASA, polycythemia ()

Inflammatory/Autoimmune Markers
Rheumatoid Factor (RF)
Antinuclear Antibodies
(ANA)
Anti-CCP/ Anti-CCP2
D-dimer
- detects IgM1 antibodies
- POOR SPECIFICTY: some RF+ wont develop RA, some RA- will develop RA
- poor disease progression marker: once a patient is RA+, they will always be RA+
- also found in normal patients, lupus, scleroderma, chronic viral infections etc.
- general test for autoimmune disorders
- if test is negative, can rule out lupus (SLE)
- multiple subtypes
- ds-DNA: specific to lupus
- ss-DNA: specific to Sjogren’s syndrome
- ANA, anti-DNP, SS-A
- SPECIFIC for RA
- tests for proteins that have changed shape due to inflammation
- appears early in the course of RA, possibly before symptoms appear (can prevent)
- order this test for patient w/ family hx of RA
- measure of inflammation
- can confirm DIC, DVT, PE, & sickle cell anemia
- should be used when high suspicion for thrombosis, wont say location of clot
- order wisely because will have to explain elevation
- can elevate due to non-inflammatory reasons like pregnancy, post-surgery, CA

Tests for Infection

Gram Stain - specimen examined under a microscope
- fast results: minutes-hrs; sample: fluid, biopsy, wound
- may guide initial antibiotic treatment
- results: gram positive: stains purple/blue; gram negative: stains pink/red; neither: will not stain (mycobacteria)
- provides morphology & arrangement BUT wont say the type of organism

Other stains to - Acid-fast: test for Tuberculosis

specifically order - Wright stain (blood): test for parasites

Culture & - very SENSITIVE & SPECIFIC

Sensitivity - will take about 48 hours to get results, do this secondary to gram stain and before antibiotic tx
- gold standard for bacterial infections
- must order specifically for fungal infections or TB
- results: will tell what bacteria it is and what antibiotics it is resistant/sensitive to and how much is needed

Antigen Detection - order blood cultures for 2 different places in the body
- order early and with high suspicion
- remember that contamination with normal skin flora is common
Nucleic Acid - viral load (HIV, Herpes)
Amplifications
Serology - not useful early on in disease because body must have time to mount a response
(antibodies) - not always indicative of current infection
- look for IgG (will stay elevated for >6 wks), IgM (will stay elevated for 4-6 wks), or both
Heart Disease Work-up: Lipid panel, Homocysteine, Apolipoproteins, Lipoprotein a, CRP

Lipid panel
HDL - good cholesterol, binds to cholesterol to get rid of it
- primary protection:
< 40 mg/dL major risk factor for CVD
40-50 mg/dL less of a risk factor for CVD
> 60 mg/dL protective against heart disease
- can increase HDL with exercise

LDL - bad cholesterol, carries cholesterol and deposits it in lining of vessels

- ideally, < 100 mg/dL in patients w/ moderate risk of HD
- want < 70 mg/dL in patients w/ known CAD or >2 risk factors (obesity, low HDL)

VLDL - carrier of triglycerides

- have capability to convert to LDL by skeletal muscles
- associated w/ increased risk of CVD
< 25% ideal
25-50% put patient at risk of CVD

Triglycerides - fat that exists in the bloodstream, transported by VLDL, produced in liver
- ideally < 160 mg/dL (male), < 135 mg/dL (female)

Total Cholesterol/HDL ratio - compares HDL and LDL in total cholesterol value
3:1 ideal

Total Cholesterol - fasting test, no food or drink (besides water) for 9-12 hrs.
- primary protection:
< 200 mg/dL desirable, low risk for CVD
200-239 mg/dL borderline high, at risk for CVD
> 240 mg/dL high cholesterol, 2x risk for CVD
- cirrhosis will  cholesterol levels

Additional tests in heart disease work-up

Homocysteine - promotes progression of atherosclerosis
>15 at risk for CVD, due to B vit. deficiency (B12, B6) dietary related, smoking, MTHFR
12-15 borderline
<12 optimal
Apolipoproteins - better indicator for CVD than HDL, LDL because precursors of HDL, LDL

Apo. A - good apolipoprotein, increased w/ exercise, decreased w/ high carb, fatty diet
- Apo A-I (75% of HDL)
- Apo A-II (20% of HDL)

Apo. B - bad apolipoprotein, increased w/ high carb, fatty diet

- Apo B-100 (found in LDL & VLDL)
- Apo B-48

Apo A-I/Apo B ratio - better measurement of comparison of Apo A & Apo B

Lipoprotein A - very bad, damages arterial walls resulting in atherosclerotic formation

- elevated in women >50 yrs old who are menopausal
RBC Abnormalities
Abnormality Appearance Possible Cause
Basophilic Stippling - fine or coarse purple dots in RBC Lead poisoning

Rouleaux - “stacked coins” Presence of disease (nonspecific)

- due to  plasma protein conc.
- affects ESR

Howell-Jolly Bodies - nuclear DNA retained in RBC Spleenectomy/ Folate Deficiency

-  room available for Hb to bind

Anisocytosis - increased variation in cell SIZE Anemia/ Blood transfusion/ Vitamin

- reported from RDW deficiency (A & B12)

Poikilocytosis - increased variation in cell SHAPE can lead to poor oxygen transportation
- many types (below)

Target Cells (Codocytes) - hemoglobinized center, target Liver disease/ Sideroblastic anemia/
appearance ETOH/ Thalassemia

Sickle Cells (Drepanocytes) - crescent shaped, stickly RBC Sickle cell anemia
- leads to early lysis & clotting due to
abnormal cell membrane

Schistocytes - fragmented RBCs, look like helmets DIC/ TTP/ HUS

Elliptocytosis - elliptical RBC Hereditary elliptocytosis (high probability)

Fe+ deficiency anemia (low probability)

Teardrop (Dacrocytes) - teardrop shaped Myelofibrosis (primarily)/ Severe Fe+

deficiency/ Megaloblastic anemia

Spherocytosis - spherical shaped, loss of central Hereditary spherocytosis

pallor
- small

Polychromasia - blue tinge to cytoplasm

- larger than normal RB
Microcytic/ Hypochromic Anemia
Type Causes/Symptoms
Fe+ deficiency Causes: insufficient Fe+ intake, inadequate gut
absorption (possible celiac disease), increased
requirement in growing children, loss of blood due to
GI bleed, menstruation, hematuria, hemorrhage
Symptoms: fatigue, exercise intolerance, koilonychia,
angular cheilosis, pica, pallor
Thalassemia What to look for: microcytic anemia with normal Fe+
levels, extremely low MCV, patient of Mediterranean,
African, or Asian decent, family hx of Thalassemia
Symptoms: may be asymptomatic depending on
severity
Chronic disease only occurs 30% of the time with microcytic anemia
Sideroblastic Causes: MC lead poisoning, myelodysplasia, chronic
alcoholism
acquired disorder with reduced Hgb synthesis causing
iron to accumulate in the mitochondria
Further Testing
- Iron: measures iron bound to transferring
- LOW
- Ferritin: measures available iron storage
- positive acute phase reactant
- LOW (<10 ng/ 100 mL)
- Transferrin: measures protein that transports iron
- negative acute phase reactant
- HIGH
-Transferrin sat: % transferrin saturated w/ iron
- LOW (<15%)
- TIBC: measures all proteins available to bind iron
- HIGH
- RBC smear
- elliptocytosis, teardrops (dacrocytes) if severe
- r/o Fe+ deficiency by checking Fe+ levels
- Hgb electrophoresis
- differentiates between HbA1, HbA2, HbS, etc.
- look for  in Alpha or Beta Hb
- RBC smear
- target cells (codocytes)
- r/o Fe+ deficiency by checking Fe+ levels
- complete patient hx
- check signs of disease/inflammation
- CRP, ESR
- Ferritin may be HIGH with inflammation
- Transferrin may be LOW with inflammation
- r/o Fe+ deficiency by checking Fe+ levels
- lead levels  HIGH
- RBC smear
- basophillic stippling or target cells (codocytes)

Normocytic/Normochromic Anemia
Type Causes/Symptoms Further Testing
Acute blood loss Causes: GI bleeds, trauma - % Reticulocytes  HIGH

Hemolytic Causes: DIC, TTP, HUS - % Reticulocytes  HIGH

- RBC smear
- schistocytes/helmet cells

Bone marrow failure Causes: aplastic anemia, leukemia, renal failure, myeloma - % Reticulocytes  LOW
- Bone marrow aspiration/biopsy  ABNORMAL

Chronic disease occurs 70% of the time with normocytic anemia -% Reticulocytes  NORMAL
- Bone marrow aspiration/biopsy  NORMAL
- CRP/ESR  ELEVATED

Macrocytic Anemia
Type Causes/Symptoms Further Testing
B12 deficiency Causes: Vegan, ileal resection, tapeworm, autoimmune - Serum B12  LOW
(pernicious anemia), megaloblastosis, inflammation of - Serum Folate  NORMAL
the ileum, nitrous oxide, bacterial overgrowth - RBC Folate  NORMAL
- MMA  HIGH
- Homocysteine  HIGH
- RBC smear
- hypersegmented PMNs may be seen
Folate deficiency Causes: Alcohol abuse, poor diet, pregnancy - Serum B12  NORMAL
- Serum Folate  LOW
Symptoms: cheilosis, glossitis, Howell-Jolly bodies, - RBC Folate  LOW
hypersegmented PMNs / megaloblastic marrow - MMA  NORMAL
(pathogonomonic) - Homocysteine  HIGH
Blood Collection Tubes
Name Contents/Purpose Labs
Yellow top tube SPS- sodium polyanethol sulfonate Blood cultures
ACD- acid citrate dextrose Blood bank studies

Anticoagulant
Light blue top tube Buffered sodium citrate Coagulation Studies
PT, PTT
Anticoagulant
Serum Separator tube Polymer gel & clot activator Calcium
(Gold or Red/Gray) Electrolytes
Separates specimen & clots within 30 min Lipids
Red top tube No additive or clot activator Chemistry

Serum collection; allows blood to clot & separates serum

from natural coagulum in 60 min
Green top tube Heparin Carboxyhemoglobin (CO)

Plasma determinations
Light green top tube Heparin & gel for plasma separation Lipids
Green/Gray top tube
PST- plasma separator tube
Lavender top tube EDTA (anticoagulant) CBC

Whole blood collection & removes calcium

Gray top tube EDTA & glycolytic inhibitor (sodium fluoride) Glucose
Primary Hemostasis Screening
Type Purpose Help to Diagnose
Platelet count Indications: thrombocytosis (>400,000/mm3) or
- petechiae, spontaneous bleeding or bleeding thrombocythemia (>1 mill/mm3)
with minor trauma (MC), increasingly heavy - due to: malignant disorders,
menses, to monitor pre-existing disease/therapy splenectomy
for thrombocytopenia/bone marrow failure
thrombocytopenia (<100,000/mm3)
- due to reduced production (bone marrow),
increased destruction, sequestration
(spleen), consumption of platelets
Platelet Assesses function of aggregation Abnormal:
aggregation - congenital platelet disorders (vWD)
Platelets stimulated in vitro, then turbidity - connective tissue disorders, uremia, CA
measured - medications

Use platelet agonists to induce aggregation

-ADP, epi, collagen, ristocetin, arachidonic acid
Bleeding time Indicator of platelet deficiency/ dysfunction Increased:
- always seen in thrombocytopenia
only test in vivo; infrequently done - vWD, dysfunctional platelet disorders,
ASA and other NSAIDs
Platelet closure Measures time required for platelets to plug a Increased:
time small hole in a tube after being exposed to -lower platelet function but doesn’t discern
various activating substances the cause
Platelet antibody Measures antibodies bound to platelet & unbound ITP (MC), DIC, maternal-fetal platelet
detection antibodies in plasma antigen incompatibility, post-transfusion
purpura

Secondary Hemostasis Screening

Type Purpose Results
PTT Activated partial thromboplsatin time Increased:
- defective intrinsic pathway
Evaluates: Factors VIII, IX, XI, XII - if coupled with  PT/INR
- defective common pathway
Affected by: Heparin, liver dysfunction, vitamin K deficiency
PT/INR Prothrombin Time/ International Normalized Ratio Increased:
- defective extrinsic pathway
Evaluates: Factor VII - if coupled with  PTT
- defective common pathway
Affected by: Coumadin (Warfarin), ETOH, liver dysfunction,
vitamin K deficiency

Coagulation Cascade Pathways

Pathway Description Factors affected Labs
Extrinsic - Initiating factor: cellular injury in vessel (tissue factor) in VII PT/INR
conjunction with platelet factors
- Fast process
Intrinsic - Initiating factor: injured subendothelial tissue comes in VIII, IX, XI, XII PTT
contact with Hageman factor (XII)
- Slow process
Common - Initiating factor: Factor X activated by the extrinsic or I, II, V, X PPT &  PT/INR
intrinsic pathway
- leads to fibrin clot
 Platelet Disorders
Thrombocytopenia
Name Background Signs/Symptoms Testing
ITP Immune Thrombocytopenia Purpura - mucosal bleeding - diagnosis of exclusion
- Acute: 2-9 yrs old w/ URI - epistaxis
- Chronic: 20-50 yr old; female>male; - menorrhagia - thorough Hx, PE
no prodromal illness - purpura - CBC: LOW plts
- autoimmune (IgG) with increase in - petechiae - blood smear: normal
destruction of platelets - normal spleen - test for HIV if suspicious
- platelet antibody detection +
- hematology consult
TTP Thrombotic Thrombocytopenia Purpura TTP Pentad: - CBC: anemia, LOW plts
- uncommon; etiology unknown - neurologic dysfunction - bone marrow: normal
- number of platelets is fine; just less - bleeding - coag. Studies: normal
circulating due to increased aggregation - hemolytic anemia - blood smear: schistocytes
- fever - LDH: HIGH
- mild renal dysfunction - indirect bilirubin: HIGH
HUS Hemolytic- Uremic Syndrome Hallmark signs: same as above but add renal
- uncommon; etiology unknown - hemolytic anemia - kidney biopsy: abnormal
- may follow viral infection, diarrheal - thrombocytopenia
illness, quinine use, pregnancy - renal failure
Non-thrombocytopenia bleeding
vWD Von Willebrand’s Disease type 1: mild bleeding disorder - CBC: normal plts
- MC congenital platelet coagulation type 2: non-functioning vWF - Plt aggregation: abnormal
disorder but enough of it to be utilized - bleeding time: prolonged
- deficiency of vWF type 3: rare; severe bleeding
- poor platelet adhesion
Miscellaneous
DIC Disseminated Intravascular Coagulation symptoms of blood clots: - CBC: hemolytic anemia
- formation of fibrin in circulation w/ - angina, SOB - Blood smear: schistocytes
fibrinolysis & depletion of coag. factors - pain, edema, warmth in legs - Platelet count: LOW
-bleeding & clotting simultaneously - PT/PTT: HIGH
- may follow Heparin use, sepsis from symptoms of bleeding: - Fibrinogen: LOW
gram negative bacteria - hematuria - D-dimer: HIGH
- can be acute or chronic - purpura, petechiae
SPD Platelet Storage Pool Disease abnormal bleeding - Blood smear: large platelets
- rare - Platelet count: variable
- deficiency of platelet granules leading - Plt aggregation: LOW or
to poor platelet aggregation absent
- MC congenital - PT/PTT: normal
- can be acquired from cardiopulmonary
bypass devices
Hypercoagulation
Factor V -MC cause of inherited thrombophilia - DVT - Coagulation assay
Leiden - activated Protein C resistance - PE
- increased thrombin activation &
promotes thrombin formation - if heterozygote (4-8x the risk)
especially in hypercoagulability states - if homozygote (80x the risk)
- pregnancy, smoking
Thyroid Labs
Name Purpose Results
TSH - SENSITIVE, best screening test for function Increased:
- responds to small changes in T3/T4 - Hypothyroidism
Decreased:
- Hyperthyroidism
Free T4 - hormone produced by the thyroid gland Increased:
- measures unbound thyroid hormone - Hyperthyroidism
- best reflection of thyroid production Decreased:
- Hypothyroidism
Total T3 - measures amount of T3 Increased:
- accurate reading - Hyperthyroidism
Decreased:
- Hypothyroidism
Total T4 - not very accurate because altered by thyroglobulin
levels
Thyroglobulin - protein produced and used within thyroid gland to
make T3/T4
- binds to T4 in the thyroid so affects total T4 levels
- do not confuse with thyroxine-binding globulin
TPO-Ab Thyroid Peroxidase Antibodies Positive: Autoimmune disease
- determines if thyroid disease is autoimmune - Graves’ disease
- tests for antibodies that attack the thyroid gland - Hashimoto’s Thyroiditis
Negative:
- thyroid dysfunction not autoimmune
Colloidal Ab Thyroid Antiglobulin Antibodies Positive:
- tests for antibodies that target thyroglobulin - Hashimoto’s Thyroiditis (85%)
- Graves’ disease (30%)
TSH Ab TSH Receptor Antibodies Positive:
- tests for antibodies that bind to TSH receptors and - Graves’ disease (test of choice)
influence outcome
- often it is a thyroid stimulating immunoglobulin
RAIU Radio Active Iodine Uptake Hot (high uptake):
- distinguishes cause of hyperthyroidism - Graves’ disease (diffuse)
- administer I- to patient and measure its uptake in the - Toxic nodular goiter (patchy)
thyroid gland - toxic adenoma (patchy)
- Hot: lots of iodine uptake in gland Cold (low uptake)
- Cold: excess hormone is not being actively made in - Thyroiditis
thyroid gland; coming from somewhere else - Thyroid CA (sometimes w/ hot patch)
Thyroid Disorders
Name Causes/Symptoms Testing
Hypothyroidism Cretinism: seen early in life; marked TSH: HIGH
physical/intellectual retardation Free T4: LOW
Myxedema: seen in older child and adult
Dx: Hashimoto’s Thyroiditis
S/S: cold intolerance, wt gain, dry skin/hair, May be 1 or 2
macroglossia, periorbital puffiness
Hyperthyroidism Thyrotoxicosis TSH: LOW
Free T4: HIGH
S/S: heat intolerance, wt loss, warm/sweaty skin,
palpitations, nervousness, exophthalmos, diarrhea Dx: Graves’ disease, toxic multinodular
goiter, toxic adenoma
Thyroid tumors can be hyper/hypo or normal thyroid function To test malignancy
- RAIU (cold) & fine needle asp. biopsy
Parathyroid Labs
Name Purpose Results
PTH Parathyroid hormone Increase:
- increase in Ca2+ - Hyperparathyroidism
- Ca2+ tubular reabsoprtion, mobilizing Ca2+ from bone
(osteoclasts), Ca2+ absorption in gut, vit D synthesis Decrease:
- decrease in Phosphorus - Hypoparathyroidism
- promotes P & HCO3- excretion
Calcitonin from parafollicluar cells of thyroid Increase:
- decreases Ca2+ - Hypoparathyroidism
- inhibits osteoclastic bone activity & promotes Ca2+
deposition in bone Decrease:
- Hyperparathyroidism

Parathyroid Disorders
Name Causes/ Symptoms Testing
Hyperparathyroidism Cause: parathyroid adenoma Primary
- PTH: HIGH
S/S: kidney stones, depression, constipation, - ionized Calcium: HIGH
osteopenia, neuromuscular dysfunction, cramps - Bone Density: LOW

Secondary (chronic)
- Ca2+ and PTH inversely proportional
Hypoparathyroidism Cause: unintentional removal from thyroid/neck PTH: LOW
surgery ionized Calcium: LOW
Phosphorous: HIGH
S/S: hx of thyroidectomy, muscle cramps,
muscle spasm esp. around mouth, fatigue,
depression, dry skin, seizures

Posterior Pituitary* Disorders

*secretes ADH (vasopressin) and oxytocin
Name Causes/ Symptoms Testing
Diabetes Insipidus insensitivity of the kidney to ADH or a deficiency Sodium: HIGH
in ADH

S/S: polyuria, polydipsia, dehydration

SIADH hyponatremia, serum hypoosmolality, high urine Sodium: LOW
osmolality & sodium concentration, normal acid- Potassium: UNCHANGED
base and potassium balance

S/S: could be asymptomatic, anorexia, malaise,

irritability, confusion
Anterior Pituitary Labs
Name Purpose Results
GH -pulsatile Stimulation test:  glucose but GH  or no
- collect specimen over 12hr period change
-Provocation testing (normal results) - Growth Hormone deficiency
- Stimulation: Insulin tolerance testing
- if  glucose then see  GH Suppression test:  glucose bur GH  or
- Suppression: Glucose ingestion no change
- if  glucose then see  GH - Acromegaly/ Gigantism
IGF-1 (inhibiting factor):
- LOW in GH deficiency
- HIGH in Acromegaly/Gigantism
Prolactin - stimulates production of milk Elevations:
- normally suppressed - Pregnancy
- order serum prolactin if suspect pituitary disease in either - Hypothyroidism
gender - Brest stimulation/ chest trauma
- Drugs: OCPs, opiates, cocaine
LH Luteinizing Hormone Primary- elevated:
- acts on ovaries and testes - PCOS
-female: stimulates estrogen production, ovulation, - Menopause
corpus luteum, peaks with FSH midcycle Secondary- decreased:
used to test infertility in spot urine test - Pituitary failure
- male: stimulates testosterone production from Leydig - Stress
cells - Anorexia nervosa
FSH Follicle- stimulating Hormone Primary- elevated:
- acts on ovaries and testes - PCOS
- female: development of follicles - Menopause
midcycle peak for follicle/ovum formation Secondary- decreased:
- male: stimulates Sertoli cell development - Pituitary failure
- Stress
- Anorexia nervosa

Anterior Pituitary Disorders

Name Causes/ Symptoms Testing
Hyperprolactinemia Cause: MC pituitary adenoma Serum Prolactin: HIGH

S/S: hypogonadism, galactorrhea, amenorrhea, headaches,

decreased libido

Anterior Pituitary Hormones

Hormone Releasing Factors Inhibiting Factors
GH GHRH Somatostatin, IGF-1
Prolactin TRH, VIP, Estradoil Dopamine
ACTH CRH, Vasopressin Cortisol
TSH TRH T4, T3, Somatostatin, Dopamine
LH GnRH Estradiol, Testosterone
FSH GnRH, Activin Inhibin, Estradoil, Testosterone
Adrenal Gland Labs
Name Purpose Results
Cortisol -glucocorticoid Elevated:
- regulated by ACTH & HPA - Cushing’s Syndrome
Aldosterone - mineralocorticoid Decreased:
- regulated by Renin-angiotensin system - Adrenal insufficiency

Adrenal Gland Disorders

Name Causes/ Symptoms Testing
Cushing’s Syndrome -many different disorders elevate cortisol Cortisol: HIGH
- Cushing’s disease: MC cause pituitary - 24 hr urinary free cortisol
adenoma or bilat adrenal hyperplasia - spit test

4 main causes: Pituitary, Adrenal, Ectopic Dexamethasone (cortisol substitute):

ACTH or CRH to determine cause
- Bilat. Adrenal Hyperplasia
S/S: HTN, wt gain, moon facies, buffalo hump - low dose = no change
- high dose =  cortisol
- Adrenal Adenoma/Carcinoma
- low dose = no change
- high dose = no change
- Ectopic ACTH
- low dose = no change
- high dose = no change

Adrenal Insufficiency Cause: 1 - destruction of adrenal cortex (MC)
2 - pituitary/ hypothalamus disorder
S/S: fatigue, weakness, fever, N/V/D,
psychosis, depression, hypotension,
dehydration, hyperpigmentation, wt loss
Cortisol: LOW (basal, urine)
Aldosterone: LOW or normal
Cosyntropin (ACTH) simulation test:
- 1 normal
- 2 rise in cortisol
Basal ACTH:
- high = Addison’s disease
- low = 2 disorder (pit/hypothal)

CT Scan to look for tumor

Arterial Blood Gases
pH/ PaCO2/ PaO2/ HCO3-/ SaO2
Normal values to know:
pH 7.35 – 7.45
PaCO2 35 – 45 mmHg
PaO2 80 – 100 mmHg
HCO3- 22 – 26 mEq/L
SaO2 95 – 100%

Abnormal ABG levels

Type Values Causes
Alveolar O2 factors that change P AO2
- PACO2
- inspired oxygen concentration
- ventilation
Hypoxemia resting PaO2 > 70 mmHg - age
- right to left shunt (anatomic or physiologic)
PaO2 < 60 mmHg = hypoxia - V/Q mismatch
- Alveolar hypoventilation (ex. sleep apnea)
- Reduced FiO2 (taking in <21% O2)
Hypercapnia PaCO2 > 45 mmHg - acute and chronic respiratory failure
- Respiratory arrest, COPD, Neuromuscular disease, V/Q mismatching
- respiratory compensation for metabolic alkalosis
Hypocapnia PaCO2 < 35 mmHg - acute anxiety
- hyperventilation
- respiratory compensation for metabolic acidosis

The approach to Acid-Base problems

pH? - Acidic < 7.35
- Alkalotic > 7.45
- If normal, check trend
- 7.35 – 7.39 = acidotic trend
- 7.41 – 7.45 = alkalotic trend
- is normal value due to compensation?

Cause? - if CO2 is abnormal and follows pH = Respiratory

-  CO2 =  pH
- If PaCO2 is normal, can be normal or no lung compensation (respiratory)
- If PaCO2 is abnormal but doesn’t follow trend, compensation occurring

- if HCO3 is abnormal and follows pH= Metabolic

-  HCO3 =  pH
- If HCO3 is normal, can be normal or no kidney compensation (metabolic)
- If HCO3 is abnormal but doesn’t follow trend, compensation occurring

- Both
Compensation? - Partial: pH is NOT within normal range lungs compensate faster than
kidneys
- Full: pH within normal range
Hypoxemia? - yes if PaO2 < 60 mmHg

**AG/OG (reference for metabolic acidosis calculations)

AG OG Ingestion Manifestations
 nl Acetaminophen Hepatitis
Salicylates Fever, tachycardia, tinnitus; metabolic acidosis + respiratory alkalosis
  Ethanol Alcoholic fetor, MS, hepatitis; keto + lactic acid = met. alk. (vomiting)
Methanol MS, blurred vision, mydriasis, papilledema
Ethylene Glycol MS, cardiopulmonary failure, hypocalcemia, Ca oxalate crystals  renal failure/ fluorescent urine
Propylene Glycol AKI
nl  Isopropyl Alcohol MS, fruity breath (acetone)
Acid/Base Abnormalities
Type Definition Causes
Respiratory Acidosis - lungs cannot remove all of CO2 - Sluggish Alveoli
- can be due to sluggish alveoli and/ or limited rib & - Asthma, COPD
lung expansion - Abnormal Rib/Lung expansion
- Scoliosis, severe obesity, Neuromuscular disorders
(ALS, myasthenia gravis, muscular dystrophy)
Respiratory Alkalosis - low levels of CO2 - Anxiety, Hyperventilation
- Mechanical ventilation (inadequate inspir./expir. ratio)
- Pneumonia, Pulmonary edema/embolism
- Sepsis
Metabolic Alkalosis - elevation of bicarbonate - H+ loss
- can be due to loss of H+ ions or inability of renal - vomiting, suction, diarrhea, diuretics (renal loss)
system to excrete bicarb - Renal insufficiency
- Hypochloremia & Hypokalemia often accompany GI - hypovolemia, heart failure
loss of H+ ions
Metabolic Acidosis - too many H+ ions - loss of bicarb
- can be due to loss of bicarb, diminished renal - diarrhea
excretion, dilution - diminished excretion
- renal failure
- dilutional
- fall in serum HCO3 due to increased fluid volume
Calculations: Anion Gap results:
Anion Gap – shows unmeasured anions - Anion gap metabolic acidosis (AGMA)
AG = measured cations – measured anions - Non-anion gap metabolic acidosis (NAGMA)
Na+ – (Cl- + HCO3-)
- if AG > 12 +/- 4 = AGMA

Metabolic Acidosis Calculations**

Type Calculation Causes
Anion Gap - differentiates types of acidosis AGMA >12
- shows unmeasured anions - MUDPILES
- Methanol, Uremia, DKA, Propylene glycol,
AG = measured cations – measured anions Isoniazid, Lactic acidosis, Ethylene glycol,
Na+ – (Cl- + HCO3-) Salicylates
- if AG > 12 +/- 4 = AGMA
* if glucose is sig. elevated, use measured Na+, not corrected NAGMA <12
- HARDUPS
Results: - Hyperalimentation (TPN), Acetozolamide use
- Anion gap metabolic acidosis (AGMA) (Rx), Renal Tubular Acidosis (RTA), Diarrhea,
- Non-anion gap metabolic acidosis (NAGMA) Uretosigmoid fistula, Pancreatic fistula. Saline,
- if low, lab error or hypoalbuminemia aggressive resuscitation
Delta Anion Gap/ - differentiates between pure acidosis or combinational
Corrected HCO3 acid/base issues
AG = patient’s AG – normal AG (use 10)

Calculate new serum HCO3

AG + SERUM HCO3 (NOT ABG!)
- if WNL, then pure metabolic acidosis
- if elevated, simultaneous alkalosis & acidosis occurring
Osmolar Gap - differentiates if an ingestent is involved MC cause is ethanol intoxication

OG = measured osmolality – calculated osmolality

Calculated osmolality =
(2*Na) + (glu/18) + (BUN/2.8) + (ETOH/ 4.6)
OG > 10 suggests ingestion