LAB.

GUIDELINE FOR FAMILY MEDICINE By Dr /Ibrahim Farouk Ahmed MRCGP EBFM NWAFH TABUK - KSA

HEMATOLOGY 1 C.B.C.
Blood : plasma ( serum + plasma proteins ) + Cells ( RBCs & WBCs & Platelets )
WBCs : Granulocytes ( Eosinophils & Neutrophils & Basophils ) + NonGranulocytes ( Lymphocytes & Monocytes )

CBC reveals :
1) White Blood Cells : 4,80010,800 cells/mm3
May be increased with infections, inflammation, cancer, leukemia decreased with some medications (such as methotrexate) some autoimmune conditions some severe infections, bone marrow failure, and congenital marrow aplasia (marrow doesn't develop normally)

2) RBCs count
In females : 4.2 -5.4 millions/cmm & In males : 4.7 6.1 millions/cmm Causes of high red cell count 1- Thalassaemia. 2`- Polycythemia vera (PRV). Causes of low red cell count include 1- Hypoproliferative anaemias, e.g. iron, vitamin B12 and folate deficiencies. 2- Aplasias e.g. idiopathic or drug-induced (dont forget chemotherapy). 3- Parvovirus B19 infection-induced red cell aplasia resulting in transient marked anaemia.

3) Hemoglobin
In females :12- 16 gm/dl & In males : 14 18gm/dl Hemoglobin Electrophoresis (Hemoglobinopathy Profile)
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Hgb A1: 9598% normal hemoglobin Hgb A2: 23% normal hemoglobin

Hgb F: 0.82%; Newborn: 5080%; _ 6 mo old: 12% (predominant fetal hemoglobin) Hgb S: 0% the predominant hemoglobin found in people with sickle cell disease.

4)Fraction of blood composed of red blood cells (Hct or PCV). Male: 42

52% Female: 3747% High PCV Polycythaemia (any cause). Low PCV Anaemia (any cause).

5) Volume of Hgb in each RBC (MCV [mean corpuscular volume]).

Male : 80 to 94fl Female : 81 99 fl MCV Iron deficiency, thalassaemia trait, Sideroblastic anaemia Normal MCV Blood loss , Myelodysplasia, Anaemia of chronic disease MCV B12 or folate deficiency, Myelodysplasia

6) Weight of the Hgb in each RBC (MCH [mean corpuscular hemoglobin]). 27

to 31 pg/cell High Macrocytosis. Low Microcytosis, e.g. iron deficiency anaemia.

7) Proportion of Hgb contained in each RBC (MCHC [mean corpuscular

hemoglobin concentration]). 33 to 37 g/Dl High Severe prolonged dehydration& Hereditary spherocytosis& Cold agglutinin disease. Low Iron deficiency anaemia& Thalassaemia

8) Red Cell Distribution Width (RDW) is a measurement of the variability of

red cell size and shape. Normal range is 11.5 to 14.5%
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 MCV with normal RDW suggests _ thalassaemia trait. MCV with high RDW suggests iron deficiency.

9) Platelets : 130,00400,000/ mm3

Decreased or increased with conditions that affect platelet production: decreased when greater numbers used, as with bleeding; decreased with some inherited disorders, with SLE , Pernicious anemia , hypersplenism (spleen takes too many out of circulation) leukemia , and chemotherapy

10 ) Mean Platelet Volume ( MPV ) ( N: 7.2 11.1 )

to determine whether or not there is an issue with the platelet production in the bone marrow. an accurate test that can easily help to determine what's wrong with platelets. If MPV shows up too low, it may be an early indicator of bone marrow cancers like leukemia.

11) Platelet distribution width ( PDW )

The PDW will be high if there are giant platelets in the presence of normal sized platelets, e.g. essential thrombocythaemia (one of the myeloproliferative disorders). The PDW will be normal in a reactive thrombocytosis (where the platelet count is increased but they are all of normal size).

DIFFERENTIAL 1 NEUTROPHILS ( N: 40 74 % )
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Neutrophilia : drugs ( corticosteroids ) & infections inflammations ( bacterial collagen disease Rheumatic fever Rheumatoid Arthritis ) Neutropenia : drugs ( chloramphenicol antithyroid antimitotic ) infections & inflammation ( bacteriasalmonella - viralhepatitis protozoalmalaria

2 LYMPHOCYTES ( N: 19 48 % )
Lymphocytosis : lymphatic leukemia acute infection TB Addison Lymphopenia : Hodgkins disease, immunodeficiency, corticosteroids & immunosuppressive drugs

3 MONOCYTES : ( N: 3.4 9 % )
Monocytosis : infections( TB typhoid endocarditis protozoal fungal )& Neoplasm ( Hodgkin carcinoma AML CML ) & GIT ( U.C Cirrhosis sarcoidosis ) N.B : Corticosteroids lead to Neutrophils & Basophiles Lymphocyte Eosinophils

4 - EOSINOPHILS ( N : 0.0 0.7 % )

Eosinophilia : Allergic disease -Parasitic - Addison Eosinopenia : Acute infections - Corticosteroids

5 BASOPHILS ( N: 0.0 1.5 )

Basophilia : myxoedoma myeloprolipherative disorders Basopenia : hyperthyroidism corticosteoids

N.B : The most common forms leukemia in adults are AML and CLL whereas
in children ALL ( acute lymphocytic leukemia ) is more .
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Critical levels:
Hgb: 5 g/dL or20 g/dL:Hgb Increased in dehydration, COPD, high altitudes, polycythemia vera. Decreased in fluid volume excess, hematologic cancers, hemolytic disorders, blood loss, anemia. Hct: 15% or 60% WBC: 500 mm3 or 50,000/ mm3,Platelets: 50,000 or 999,000/mm3

Peripheral blood film

When to request a blood film examination :
if the patients indices are abnormal (unless there has been no major change from previous CBCs). If you suspect an underlying blood disorder you should request a film.

Information from the blood film :

Red cells(Size. Shape. Membrane changes (e.g. oxidative membrane damage). Colour.
Basophilic stippling. Inclusions, e.g. Howell- Jolly bodies, malarial parasites, HbC crystals, etc.)

White cells(Number. Morphology. Abnormalities such as toxic granulation, dysplastic

changes. Presence of abnormal cells, e.g. leukaemic blasts or lymphoma cells.) Platelets(Number. Size. Shape.) Other features on the film(2 Parasites2 Red cell Rouleaux Blood film when WBC is

What cell predominates?

1) Lymphocytes? suggests viral, CLL, acute leukaemia (lymphoblastic). 2) Granulocytic? (neutrophils, eosinophils, basophils)may be reactive or CML. 3) Abnormal looking WBC? Look for Auer rods (AML), smear cells(CLL), bilobed
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neutrophils (pseudo-Pelger cells seen in myelodysplastic syndrome (MDS ).

FERRITIN (serum)
Normal range: 18-300 ng/ml (18-300 g/L [CF: 1; SMI: 10 g/L]) Elevated in: Hyperthyroidism, inflammatory states, liver disease (ferritin elevated
from necrotic hepatocytes), neoplasms (neuroblastomas, lymphomas, leukemia, breast carcinoma), iron replacement therapy, hemochromatosis, hemosiderosis

Decreased in: Iron deficiency anemia

Reticulocytes
Normal range: 0.52.5% (50100 109/L). immature RBCS formed in the marrow and found in small numbers in normal peripheral blood. They represent an intermediate maturation stage in marrow between the nucleated RBC and the mature RBC. useful measure of response to haematinic (iron, B12 or folate) replacement therapy.

Causes of reticulocyte counts

Marrow stimulation due to 1) Bleeding. 2) Haemolysis. 3) Response to oral Fe therapy. 4) Infection. 5) Inflammation. 6) Polycythaemia (any cause). 7) Myeloproliferative disorders. 8) Erythropoietin administration. 9) Marrow recovery following chemotherapy or radiotherapy. Causes of reticulocyte counts Marrow infiltration due to 1) Leukaemia. 2) Myeloma. 3) Lymphoma. 4) Other malignancy.

How To Evaluate CBC Report

Low Hb=Anemia MCV

Low microcytic Measure Ferritin Low Iron def Anemia Normal/high

Normal normocytic

High macrocytic Measure B12 + folate Normal Low Megaloblastic anemia

Anemia of chronic disease/ Congenital Hb dis.

Reticulocyte count

Hemolytic anemia or blood loss

high

low

Anemia of chronic disease Renal failure Marrow failure

Check RBCs
M/mm >5.5 M/mm Polycythemia Check WBCs + plat 4.5-5.5M/cmm 4.5-5.5M/cmm Normal Check WBCs + plat WBCs <4.5M/cmm <4.5M/cmm Anemia Check WBCs + plat+ coag.time WBCs but Not >20.000

All PRV

WBCs (N) Plat

2ry poly

Leucopenia + Relative Lymphocytosis

Leucocytosis
Check for Differential count L M N

Anemia
Check WBCs + plat+ coag.time WBCs + All N Coag T Plat Hemophilia Thrombocytopenia Pancytopenia Leukemia WBCs >20000 Platelets
Blast Blast Cell Cell

MCV No Ch L
CML CLL

Yes AL

N
Micro A Micro A Macro A Macro A H A + H A +

PRV Polycythemia rubra vera

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Types of Anemias
Type of Anemia Possible Causes

Normocytic/normochromic Acute blood loss, aplastic anemia, (normal cell size; normal amount of Hgb) prosthetic heart valves, sepsis, tumor Microcytic/hypochromic (small cell size; low amount of Hgb) Microcytic/normochromic (small cell size; normal amount of Hgb) Macrocytic/normochromic (large cell size; normal amount of Hgb) Iron deficiency, lead poisoning, thalassemia Erythropoietin deficiency secondary to renal failure Chemotherapy, folate deficiency, vitamin B12 deficiency

BLOOD GROUPING
1 - ABO blood group system is the most important blood type system (or blood
group system) in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses.

2 - Rh factor
is written as either positive (present) or negative (absent). Most people are Rh positive. The Rh blood group system currently consists of 50 defined blood-group antigens, among which the 5 antigens D, C, c, E, and e are the most important ones. the D antigen, is a relevant cause of the hemolytic disease of the newborn or erythroblastosis fetalis .

3- DIRECT COOMBS
Normal: Negative
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Positive: Autoimmune hemolytic anemia, erythroblastosis fetalis, transfusion reactions, drugs (-methyldopa, penicillins, tetracycline, sulfonamides, levodopa, cephalosporins, quinidine, insulin) False positive: May be seen with cold agglutinins

4 - INDIRECT COOMBS
Normal: Negative Positive: Acquired hemolytic anemia, incompatible cross-matched blood, anti-Rh antibodies, drugs (methyldopa, mefenamic acid, levodopa)

HEMATOLOGY - II COAGULATION
1 - PROTHROMBIN TIME (PT)
Normal range: 10-12 sec Elevated in: Liver disease, oral anticoagulants (warfarin), heparin, factor deficiency (I, II, V, VII, X), disseminated intravascular coagulation, vitamin K deficiency, afibrinogenemia, dysfibrinogenemia, drugs (salicylate, chloral hydrate, diphenylhydantoin, estrogens, antacids, phenylbutazone, quinidine, antibiotics, allopurinol, anabolic steroids) Decreased in: Vitamin K supplementation, thrombophlebitis, drugs (glutethimide, estrogens, griseofulvin, diphenhydramine)

2 - INTERNATIONAL NORMALIZED RATIO (INR)

NORMAL RANGE : 0.7 1.3
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Recommended INR ranges: Proximal deep vein thrombosis: 2-3 Transient ischemic attacks: 2-3 Mechanical prosthetic valves: 3-4.5 Recurrent venous thromboembolic disease: 3-4.5 Pulmonary embolism: 2-3 Atrial fibrillation: 2-3

3 - PARTIAL THROMBOPLASTIN TIME (PTT) OR ACTIVATED PARTIAL THROMBOPLASTIN TIME (APTT)

Normal range: 23-32 sec Elevated in: Heparin therapy, coagulation factor deficiency (I, II, V, VIII, IX, X, XI, XII), liver disease, vitamin K deficiency, disseminated intravascular coagulation, circulating anticoagulant, warfarin therapy, specific factor inhibition (PCN reaction, rheumatoid arthritis), thrombolytic therapy, nephrotic syndrome Note: Useful to evaluate the intrinsic coagulation system.

4 - FIBRINOGEN
Normal range: 200-400 mg/dl Elevated in: Tissue inflammation or damage (acute phase protein reactant), oral contraceptives, pregnancy, acute infection, myocardial infarction Decreased in: Disseminated intravascular coagulation, hereditary afibrinogenemia, liver disease, primary or secondary fibrinolysis, cachexia

5 - THROMBIN TIME (TT)

Normal range: 15-18 sec
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Elevated in: Thrombolytic and heparin therapy, disseminated intravascular coagulation, hypofibrinogenemia, dysfibrinogenemia

6 FIBRIN DEGRADATION PRODUCT (FDP )

Normal Range : Less Than 10 ug/ml The FDP assay has been available as a screening test for the diagnosis of disseminated intravascular coagulation (DIC) The FDP assay detects fibrinolytic breakdown products of fibrinogen and crosslinked fibrin, and is positive in both primary fibrinolysis (primary activation of the fibrinolytic pathway) and secondary fibrinolysis (usually associated with DIC).

7 FACTOR VIII
Descriptive Name : Antihemophilic factor or globulin Source : Endothelial cells and (?) elsewhere Approximate Half-Life (hr) : 12 h Function : Cofactor intrinsic pathway (IP)

8 FACTOR IX
Descriptive Name : Plasma thromboplastin component, Christmas factor Source : Liver vitamin K dependent (VKD) Approximate Half-Life (hr) : 24 h Function : Serine protease intrinsic pathway (IP)

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Coagulation Lab.
Diagnosis Platelet function defect, XII def. normal N N N VII def., early oral anticoagulants N N N VIII,IX,XI,XII def. VWD,circulating anticoagulant e.g. lupus N N Vit.K def. ,oral anticoagulants , V,VII,X,II def. N Heparin , liver disease , fibrinogen def N N N Thrombocytopenia ( any cause ) N Massive transfusion ., liver disease DIC , Acute liver disease def., deficiency; N, normal; , increased; , decreased. PT:prothrombin time APTT: Activated partial thromboplastin time TCT: Thrombin clotting time N.B : Hemophilia A = Factor VIII Deficiency Hemophilia B = Factor IX Deficiency , Christmas disease PT N APTT N TCT N Platelets N

Screening tests for coagulation system

Bleeding T Platelet & BV function

Prothrombin T Extrinsic Pathway( factors V,VII .X , Prothrombin , fibrinogen ) a PTT Intrinsic pathway ( factors V.VIII,IX.X,XI.XII,Fibrinogen ) Thrombin. T Both pathways. (DIC)

Coagulation time (clotting time)

Coagulation time is the time required for blood to coagulate or it is the time passes between the start of bleeding and the formation of a clot.
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 A normal coagulation time in a healthy person is between 3 and 8 min. Prolonged in haemophilia and in the presence of obstructive jaundice, some anaemias and leukaemias, and some of the infectious diseases.

Bleeding time
It is the time elapsed between the formation of a small cut and the stoppage of bleeding from the cut blood vessel. The normal range of bleeding time is between 1 and 3 min. Significance: this test does not depend on the coagulation mechanism of blood but on the efficiency of vasoconstriction of injured vessels. Therefore, bleeding time is normal in haemophilia and is prolonged in purpura.

CHEMISTRY 1 Electrolytes Urea Creatinine

1 Sodium
Normal range: 135-145 mmol/L

HYPONATREMIA
A - Sodium and water depletion (deficit hyponatremia) 1 - Loss of gastrointestinal secretions with replacement of fluid but not electrolytes a Vomiting b - Diarrhea c - Tube drainage 2 - Loss from skin with replacement of fluids but not electrolytes a - Excessive sweating b- Extensive burns 3 - Loss from kidney
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a Diuretics b - Chronic renal insufficiency (uremia) with acidosis 4 - Metabolic loss a - Starvation with acidosis b - Diabetic acidosis 5 - Endocrine loss a - Addison's disease b - Sudden withdrawal of long-term steroid therapy 6 - Iatrogenic loss from serous cavities a - Paracentesis or thoracentesis B- Excessive water (dilution hyponatremia) 1 - Excessive water administration 3 Cirrhosis 5 - Hypoalbuminemia (severe) 2 - Congestive heart failure 4 - Nephrotic syndrome 6 - Acute renal failure with oliguria

C- Inappropriate antidiuretic hormone (IADH) syndrome D - Intracellular loss (reset osmostat syndrome) E - False hyponatremia (actually a dilutional effect) 1 - Marked hypertriglyceridemia* 2 - Marked hyperproteinemia* 3 - Severe hyperglycemia

HYPERNATREMIA
Dehydration is the most frequent overall clinical finding in hypernatremia. 1 - Deficient water intake (either orally or intravenously) 2 - Excess kidney water output (diabetes insipidus, osmotic diuresis) 3 - Excess skin water output (excess sweating, loss from burns) 4 - Excess GIT output (severe protracted vomiting or diarrhea without fluid therapy)

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5 - Accidental sodium overdose 6 - High-protein tube feedings

2 - POTASSIUM
Normal range: 3.2-5.0 mmol/L

CAUSES OF HYPERKALEMIA
1 Pseudohyperkalemia a - Hemolysis of sample b Thrombocytosis c Leukocytosis d - Laboratory error 2 - Increased potassium intake and absorption a - Potassium supplements (oral and parenteral) b - Dietarysalt substitutes c - Stored blood d - Potassium-containing medications

3 - Impaired renal excretion a - Acute renal failure b - Chronic renal failure c - Tubular defect in potassium secretion d Hypoaldosteronism 4 - Transcellular shifts a Acidosis b Hypertonicity c - Insulin deficiency d Drugs (-blockers , Digitalis toxicity , Succinylcholine ) e Exercise f - Hyperkalemic periodic Paralysis 5 - Cellular injury a Rhabdomyolysis b - Severe intravascular hemolysis c- Acute tumor lysis syndrome d - Burns and crush injuries

CAUSES OF HYPOKALEMIA
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I - Decreased intake a - Decreased dietary potassium b - Impaired absorption of potassium c - Clay ingestion d - Kayexalate II - Increased loss Renal A Hyperaldosteronism 1 Primary : Conn's syndrome & Adrenal hyperplasia 2- Secondary : Congestive heart failure & Cirrhosis & Nephrotic syndrome &Dehydration 3- Bartter's syndrome B - Glycyrrhizic acid (licorice, chewing tobacco) CExcessive adrenal corticosteroids

1 - Cushing's syndrome 2 - Steroid therapy 3 - Adrenogenital syndrome D - Renal tubular defects 1 - Renal tubular acidosis 2 - Obstructive uropathy 3 - Salt-wasting Nephropathy E Drugs 1 Diuretics 2 Aminoglycosides 3 Mannitol 4 Amphotericin 5 Carbenicillin Gastrointestinal 1 Vomiting 2 - Nasogastric suction 3 Diarrhea 4 Malabsorption 5 Ileostomy 6 - Villous adenoma 7 - Laxative abuse

Increased losses from the skin

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1 - Excessive sweating III - Transcellular shifts

2 Burns

A Alkalosis : 1-Vomiting 2- Diuretics 3- Hyperventilation 4- Bicarbonate therapy B Insulin : 1 Exogenous 2 - Endogenous response to glucose C - 2-Agonists (albuterol, terbutaline, epinephrine) D - Hypokalemia periodic paralysis : 1- Familial 2- Thyrotoxic IV Miscellaneous A- Anabolic state B - Intravenous hyperalimentation

C- Treatment of megaloblastic anemia D - Acute mountain sickness

3 - CHLORIDE (serum)
Normal range: 96-106 mmol/L Elevated in: Dehydration, excessive infusion of normal saline solution, cystic fibrosis (sweat test), hyperparathyroidism, renal tubular disease, metabolic acidosis, prolonged diarrhea, drugs (ammonium chloride administration, acetazolamide, boric acid, triamterene) Decreased in: Congestive heart failure, syndrome of inappropriate antidiuretic hormone secretion, Addison's disease, vomiting, gastric suction, salt-losing nephritis, continuous infusion of D5W, thiazide diuretic administration, diaphoresis, diarrhea, burns, diabetic ketoacidosis

4 Bicarbonate Normal range : 19 24 mmol/L

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5 - Serum urea {Blood Urea Nitrogen (BUN) }

Normal Results: Adult: 1020 mg/dL; SI units: 3.67.1 mmol/L Child: 416 mg/dL; SI units: 1.45.7 mmol/L Elevated BUN (azotemia) occurs in most renal diseases; also rises with GI bleeding, dehydration, high protein diet, and CHF.

Abnormal Results
Higher-than-normal Congestive heart failure Excessive protein levels in the gastrointestinal tract Gastrointestinal bleeding Hypovolemia Heart attack Kidney disease, including GN, pyelonephritis, and ATN Kidney failure Shock Urinary tract obstruction Lower-than-normal Liver failure Low protein diet Malnutrition Over-hydration Critical Levels: 40 mg/dL (not dehydrated/no history of renal disease) 100 mg/dL (patient with history of renal disease) 20 mg/dL increase in 24 hr (indicates acute renal failure)

6 - Serum creatinine
A normal value : Adult: Male: 0.61.2 mg/dL; SI units: 53106 _mol/L.

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Female: 0.51.1 mg/dL; SI units: 4497 _mol/L & Child: 0.30.7 mg/dL N.B : Females usually have a lower creatinine than males, because they usually have less muscle mass. Causes of Abnormal Creatinine Other Than Renal Diseases Acetoacetate and cephalosporins High meat intake, strenuous exercise, drugs (as salicylate) age and sex (less in children and females). Pregnancy causes Reduced muscle bulk (starvation, wasting disease, steroids) Abnormal Results Higher-than-normal Acute tubular necrosis Dehydration Diabetic nephropathy Eclampsia Glomerulonephritis Kidney failure Muscular dystrophy Preeclampsia Pyelonephritis Reduced kidney blood flow (shock, congestive heart failure) Rhabdomyolysis Urinary tract obstruction Lower-than-normal Muscular dystrophy (late stage) Myasthenia gravis

- Creatinine Clearance
It compares the level of creatinine in urine with the creatinine level in the blood. Requires a 24-hour urine collection. Requires serum creatinine assay. Declines by 1mL/min/year >40 years.

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Normal Results
Male: 97 to 137 ml/min. Female: 88 to 128 ml/min. N.B : Creatinine clearance of 1020 mL/min is indicative of renal failure and the need for dialysis.

Abnormal results
Acute tubular necrosis Bladder outlet obstruction Congestive heart failure Dehydration Glomerulonephritis Renal ischemia Renal outflow obstruction (usually must affect both kidneys to reduce the creatinine clearance) Shock Renal failure (acute, chronic & ESRD)

Considerations
Factors that may interfere with the accuracy of the test are: Incomplete urine collection Pregnancy Vigorous exercise Drugs (cimetidine, trimethoprim, and drugs that can damage the kidneys, such as cephalosporins)

STAT TESTS OTHER THAN ABOVE 1 - CALCIUM (serum)

Normal range: 8.8-10.3 mg/dl (2.3-2.64 mmol/L

Elevated in:
Relatively Common 1 - Neoplasia (noncutaneous) a - Bone primary b Myeloma c - Acute leukemia 2 - Nonbone solid tumors a Breast b - Lung
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3 - Squamous nonpulmonary a - Kidney 4 - Neoplasm secretion of parathyroid hormone-related protein (PTHrP, ectopic PTH) 5 - Primary hyperparathyroidism 6 - Thiazide diuretics 7 - Tertiary (renal) hyperparathyroidism 8 Idiopathic 9 - Spurious (artifactual) hypercalcemia 10 Dehydration 11- Serum protein elevation RELATIVELY UNCOMMON 1 - Neoplasia (less common tumors) 2 Sarcoidosis 3 - Hyperthyroidism 4 - Immobilization (mostly seen in children and adolescents) 5 - Diuretic phase of acute renal tubular necrosis 6 - Vitamin D intoxication 7 - Milk-alkali syndrome 8 - Addison's disease 9 - Lithium therapy 10 - Idiopathic hypercalcemia of infancy 11- Acromegaly 12- Theophylline toxicity 12 - Laboratory technical problem

DECREASED IN :
1 Artifactual 2 Hypoalbuminemia 3 Hemodilution 4 - Primary hypoparathyroidism 5 Pseudohypoparathyroidism 6 - Vitamin Drelated 7 - Vitamin D deficiency 8 - Gentamicin

9 Malabsorption 10 - Renal failure 11 - Magnesium deficiency 12 - Sepsis 13 - Chronic alcoholism 14 - Tumor lysis syndrome 15 Rhabdomyolysis 16 - Cimetidine 17 - Alkalosis (respiratory or metabolic) 18 - Acute pancreatitis 19 - Drug-induced hypocalcemia 20 - Large doses of magnesium sulfate 21 Anticonvulsants 22 Mithramycin

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2 - AMYLASE (serum)
Normal range: 0-220 U/L

Elevated in:
Acute pancreatitis, pancreatic neoplasm, abscess, pseudocyst, ascites, macroamylasemia, perforated peptic ulcer, intestinal obstruction, intestinal infarction, acute cholecystitis, appendicitis, ruptured ectopic pregnancy, salivary gland inflammation, peritonitis, burns, diabetic ketoacidosis, renal insufficiency, drugs (morphine), carcinomatosis (of lung, esophagus, ovary), acute ethanol ingestion, mumps, prostate tumors, postendoscopic retrograde cholangiopancreatography, bulimia, anorexia nervosa

Decreased in:
Advanced chronic pancreatitis, hepatic necrosis, cystic fibrosis

LIVER FUNCTION TESTS

1- TOTAL PROTEIN (N : 65 64 g/l )

A Albumin ( N: 38 53 ) :
A falling serum albumin in liver disease bad prognosis This is a marker of synthetic function Guide to the severity of chronic liver disease. In acute liver disease initial albumin levels may be normal

B Globulin : Seen in liver disease, usually due to increased immunoglobulins .

2 ALKALINE PHOSPHATASE ( N : 36 125 U/L ) Present in the canalicular and sinusoidal membranes of the liver.
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 Also, in many other tissues, such as bone, intestine and plasma. If there is also an abnormality e.g. -GT, ALP can be presumed to come from the liver.
Cholestasis markers: alkaline phosphatase, The highest serum levels due to liver disease >1oooIU/L Are seen in hepatic metastasis and 1ry biliary cirrhosis

3 TOTAL BILIRUBIN ( N : 2 22 UMOL/L )

Bilirubin : 2 Forms Unconjugated (indirect)- insoluble in hemolysis, Gilbert syndrome, meds Conjugated (direct)- soluble in obstruction, cholestasis, cirrhosis, hepatitis, primary biliary cirrhosis, etc. Conjugated bilirubin is not elevated until liver loses >50% excretory capacity.

4 ALT ( N : 3 36 U/L )
ALT : A rise only occur with liver disease. Minimal ALT elevations (<1.5 X normal) in cases of Obesity , Muscle injury N.B : Transaminases may NOT be elevated in chronic liver disease HCV & Cirrhosis N.B : Mild Transaminases Increase (AST/ALT < 5 times upper limit of normal ) ALT-predominant (Chronic HCV , Chronic HBV , Acute viral hepatitis , Wilsons Disease , Hemochromatosis , Medications/Toxins , Autoimmune Hepatitis , Alpha1 Antitrypsin def

5 AST ( N: 0 37 U/L )
AST : Not Specific in cases of Hepatic necrosis , MI, CHF , Ms injury AST predominant (Alcohol , Cirrhosis , Non-hepatic as Myopathy , Hemolysis , Thyroid disease , Strenuous exercise )

CARDIAC ENZYMES
1 CPK ( N: 50 200 U/L
Rises within 4-8 hr for 48 hrs. MB iso-enzyme of CK is more specific as it is found mainly in cardiac muscle.
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2 - LACTATE DEHYDROGENASE (LDH)

Normal range: 230 460 U/L Elevated in:
1 - Infarction of myocardium, lung, kidney 2 - Diseases of cardiopulmonary system, liver, collagen, central nervous system 3 - Hemolytic anemias, megaloblastic anemias, transfusions 4 - seizures, muscle trauma, muscular dystrophy, acute pancreatitis 5 - hypotension, shock, infectious mononucleosis, inflammation, neoplasia 6 - intestinal obstruction, hypothyroidism

3 - Troponin T & I

Is a protein of sarcomere, not normally present in blood . Rises 2-4 hr after MI, remain raised 5-14d Therefore replace LDH for diagnosis of MI.

4 - Other Non-specific Laboratory Tests

PML Leucocytosis (12.000-15000 /L) CRP ESR TEST CK/CK-MB Troponins Myoglobin LDH Timing Summary ONSET PEAK 3-12 hours 3-12 hours 1-4 hours 6-12 hours 18-24 hours 18-24 hours 6-7 hours 24-48 hours DURATION 36-48 hours Up to 10 days 24 hours 6-8 days

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CHEMISTRY II 1 CHOLESTEROL ( N : 2.7 6.35 mmol/L )

Elevated in:
1 - Primary hypercholesterolemia

2 - biliary obstruction, 4 - nephrotic syndrome 6 - primary biliary cirrhosis 8 - pregnancy third trimester

3 - diabetes mellitus 5 - hypothyroidism, 7 - high-cholesterol diet, 9 - myocardial infarction

10 - drugs (steroids, phenothiazines, oral contraceptives)

Decreased in:
1 Starvation

2 malabsorption 5 abetalipoproteinemia 8 - hepatic failure

3 - sideroblastic anemia, 6 hyperthyroidism 9 - multiple myeloma

4 thalassemia 7 - Cushing's syndrome 10 - polycythemia vera 12 - myeloid metaplasia 14 myelofibrosis

11 - chronic myelocytic leukemia 13 - Waldenstrm's macroglobulinemia

A - HIGH-DENSITY LIPOPROTEIN (HDL) CHOLESTEROL

Normal range:
Male: 40-70 mg/dl (0.8-1.8 mmol/L ) Female: 50-90 mg/dl (1.1-2.35 mmol/L )

Increased in:
1 - Use of gemfibrozil, statins, fenofibrate, nicotinic acid, estrogens 2 - regular aerobic exercise 3 - small (1 oz) daily alcohol intake

Decreased in:
1 - Deficiency of apoproteins 26

2 - liver disease

Note: A cholesterol/HDL ratio >4.0 is associated with increased risk of coronary artery disease. HDL levels 60 mg/dL are protective against heart disease.

B- LOW-DENSITY LIPOPROTEIN (LDL) CHOLESTEROL

Normal range: 50-130 mg/dl (1.30-1.68 mmol/L
LDL cholesterol <70 Optimal in diabetics, prior MI, and patients with cardiac risk factors

100-129 Near or above optimal 130-159 Borderline high 160-189 High 190 Very high

Lipid Goals in Patients With Atherosclerotic Disease or Diabetes

LDL* cholesterol <100 mg/dl <70 mg/dl (option in very high-risk patients) Total Cholesterol <200 mg/dl HDL cholesterol >40 mg/dl (men), >50 mg/dl (women) Triglycerides <150 mg/dl Lipid panels typically use a calculated LDL. The calculated LDL = [Total cholesterol (Triglycerides/5)] HDL. This formula is applicable only when Triglycerides are <400 mg/dl.

2 TRIGLYCERIDE ( N : 0.3 2.15 mmol/L )

Elevated in:
1 - Hyperlipoproteinemias (types I, IIb, III, IV, V) 2 - hypothyroidism

3 estrogens 4 - acute myocardial infarction 5 - pancreatitis 6 - alcohol intake 7 - nephrotic syndrome 8 - diabetes mellitus 9 - glycogen storage disease 10 - pregnancy

Decreased in:
1 Malnutrition

2 - congenital abetalipoproteinemias

3 - drugs (e.g., gemfibrozil, fenofibrate, nicotinic acid, clofibrate)

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3 FASTING GLUCOSE

Diagnosis of DM is made on the basis of the following tests and should be confirmed by repeated testing on a different day: 1. 2. Fasting glucose 126 mg/dl Nonfasting plasma glucose200 mg/dl + symptoms

Normal range: 70-110 mg/dl (3.9-6.1 mmol/L Elevated in: Diabetes mellitus, stress, infections, myocardial infarction, cerebrovascular accident, Cushing's syndrome, acromegaly, acute pancreatitis, glucagonoma, hemochromatosis, drugs (glucocorticoids, diuretics [thiazides, loop diuretics]), glucose intolerance Decreased in: Sulfonylurea therapy, insulin therapy, reactive hypoglycemia (e.g., s/b subtotal gastrectomy), starvation, insulinoma, glycogen storage disorders, severe liver disease or renal disease, ethanol-induced hypoglycemia, mesenchymal tumors that secrete insulin-like hormones

GLUCOSE, POSTPRANDIAL
Normal range: <140 mg/dl (<7.8 mmol/L [CF: 0.05551; SMI: 0.1 mmol/L]) Elevated in: Diabetes mellitus, glucose intolerance Decreased in: Postgastrointestinal resection, reactive hypoglycemia, hereditary fructose intolerance, galactosemia, leucine sensitivity

GLUCOSE TOLERANCE TEST

Normal values above fasting: 30 min: 30-60 mg/dl (1.65-3.3 mmol/L [CF: 0.05551; SMI: 0.1 mmol/L])

28

60 min: 20-50 mg/dl (1.1-2.75 mmol/L [CF: 0.05551; SMI: 0.1 mmol/L]) 120 min: 5-15 mg/dl (0.28-0.83 mmol/L [CF: 0.05551; SMI: 0.1 mmol/L]) 180 min: fasting level or below Abnormal in: Glucose intolerance, diabetes mellitus, Cushing's syndrome, acromegaly, pheochromocytoma, gestational diabetes

Severe Hypoglycemia (SH) Patient Men Women Infant and children Term infants Pre-term infants Serum Glucose 50 md/dL 45 md/dL 40 md/dL 30 md/dL 20 md/dL

4 CALCIUM : See CHEMISTRY - I 5 PHOSPHATE (serum)

Normal range: 2.5-5 mg/dl (0.65-1.3 mmol/L

DECREASED IN :
1 Parenteral hyperalimentation 2 Diabetic acidosis 3 Alcohol withdrawal 4 Severe metabolic or respiratory alkalosis 5 Antacids that bind phosphorus 6 Malnutrition with refeeding using low-phosphorus nutrients 7 Renal tubule failure to reabsorb phosphate (Fanconi's syndrome; congenital disorder; vitamin D deficiency) 8 Glucose administration 9 Nasogastric suction 10 Malabsorption 11 Gram-negative sepsis
29

12 Primary hyperthyroidism 13 Chlorothiazide diuretics 14 Therapy of acute severe asthma 15 Acute respiratory failure with mechanical ventilation

INCREASED IN :
1 Renal failure 2 Severe muscle injury 3 Phosphate-containing antacids 4 Hypoparathyroidism 5 Tumor lysis syndrome

6- MAGNESIUM (serum)
Normal range: 1.8-3.0 mg/dl (0.74-1.00 mmol/L
CAUSES OF HYPERMAGNESEMIA I Decreased renal excretion a Renal failureglomerular filtration rate less than 30 ml/min b Hyperparathyroidism c Hypothyroidism d Addison's disease e Lithium intoxication f Familial hypocalciuric hypercalcemia II Other causes: usually in association with decrease in glomerular filtration rate A- Endogenous loads : Diabetic ketoacidosis & Severe tissue injuryburns B Exogenous loads : 1 Gastrointestinal : Magnesium-containing laxatives and antacids & High-dose vitamin D analogs 2 Parenteral: management of toxemia of pregnancy

CAUSES OF HYPOMAGNESEMIA
A Alcoholic abuse C Renal losses 1 Acute and chronic renal failure 2 - -Postobstructive diuresis 3 Acute 4 Chronic glomerulonephritis 5 Chronic pyelonephritis 6 Interstitial nephropathy 7 Renal transplantation
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B Diuretic use

D Gastrointestinal losses 1 Chronic diarrhea 2 Nasogastric suctioning 3 Short bowel syndrome 4 Protein calorie malnutrition 5 Bowel fistula 6 Total parenteral nutrition 7 Acute pancreatitis E Endocrine 1 Diabetes mellitus 2 Hyperaldosteronism 3 Hyperthyroidism 4 Hyperparathyroidism F Pregnancy G Drugs 1 Aminoglycosides 2 Amphotericin 3 -Agonists 4 Cisplatin 5 Cyclosporine 6 Diuretics 7 Foscarnet 8 Pentamidine 9 Theophylline H Congenital disorders 1 Familial hypomagnesemia 3 Maternal hypothyroidism 2 Maternal diabetes 4 Maternal hyperparathyroidism 5 Acute intermittent porphyria

7 LITHIUM ( N: 0.5 1.6 mmol/L ) 8 AMYLASE ( N: 0 220 U/L ) See CHEMISTRY I 9 IRON
( N: 9 -36 umol/L Male & 7 33 umol/L Female & Child 6 mo2 yr: 40100 _g/dL; SI units: 7.1617.9 _mol/L ) Iron is critical to proliferation and maturation of red blood cells. 65% of iron is found in hemoglobin. Most of the rest is stored as ferritin in in the liver, bone marrow, and spleen. Transferrin is the major transporting protein of iron.
31

 Increased in excessive iron intake and decreased production of erthrocytes. Decreased in iron deficiency anemia, normochromic anemia associated with chronic diseases.

10 - TOTAL IRON-BINDING CAPACITY (TIBC)

Normal range: 47 66 umol/l Elevated in:
1 - Iron deficiency anemia

2 pregnancy 5 - weight loss

3 polycythemia

4 - hepatitis

Decreased in:
1 - Anemia of chronic disease 4 - hemolytic anemias 2 hemochromatosis 3 - chronic liver disease 5 - malnutrition (protein depletion)

11 -glutamyl transpeptidase ( GGT )

( N : 7 42 U / L ) GGT elevated in isolation (normal LFTs) alcohol use & anticonvulsant use (dilantin) without liver disease Persistent elevated in asymptomatic women 1ry biliary cirrhosis (check AMA) Most mild elevations (<1.5 X normal) will have no identifiable etiology and will normalize within 6 months

12 AMMONIA
Elevated in:
1 - Hepatic failure

2 hepatic encephalopathy
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3 Reye's syndrome

4 portacaval shunt 5 drugs (diuretics, polymyxin B, methicillin)

Decreased in:
1 Drugs (neomycin, lactulose, tetracycline)

2 renal failure

13 TOTAL ACID PHOSPHATASE

( N : 0 0.8 U/L )

Abnormal results
The highest levels of acid phosphatase are found in metastasized prostate cancer. Diseases of the bone, such as Paget's disease or hyperparathyroidism; diseases of blood cells, such as sickle cell disease or multiple myeloma; or lysosomal disorders, such as Gaucher's disease, will show moderately increased levels. Certain medications can cause temporary increases or decreases in acid phosphatase levels. Manipulation of the prostate gland through massage, biopsy, or rectal exam before a test can increase the level. N.B : Acid phosphatase from the prostate, called prostatic acid phosphatase (PAP), is the most medically significant type of acid phosphatase.

14 HDL See TOTAL CHOL. 15 CKMB See cardiac Enzymes

(N:6%)

16 OSMOLALITY
( N : BLOOD 275 295 mosm / kg & URINE 50 1400 mosmol / L )

Elevated in:
1 Dehydration 4 - uremia 2 - hypernatremia 5 - hyperglycemia 3 - diabetes insipidus 6 - mannitol therapy

7 - ingestion of toxins (ethylene glycol, methanol, ethanol)

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8 hypercalcemia

9 - diuretics

Decreased in:
1 - Syndrome of inappropriate diuretic hormone secretion 2 - hyponatremia, overhydration 3 - Addison's disease 4 - hypothyroidism

17 URIC ACID
( N : 0.21 0.48 mmol /L ) 2-7 mg/dl

Elevated in:
1 - Renal failure 2 gout 3 - polycystic kidneys 4 - acidosis

5 - excessive cell lysis (chemotherapeutic agents, radiation therapy, leukemia, lymphoma, hemolytic anemia) 6 - hereditary enzyme deficiency (hypoxanthine-guanine-phosphoribosyl transferase) 7 - myeloproliferative disorders 9 - lead poisoning

8 - diet high in purines or protein

10 - drugs (diuretics, low doses of ASA, ethambutol, nicotinic acid) 11 hypothyroidism 12 - Addison's disease 13 - active psoriasis

14 - nephrogenic diabetes insipidus

Decreased in:
1 - Drugs (allopurinol, high doses of ASA, probenecid, warfarin, corticosteroid) 2 - deficiency of xanthine oxidase 3 - renal tubular deficits (Fanconi's syndrome) 4 - syndrome of inappropriate antidiuretic hormone secretion 5 alcoholism 6 - liver disease 7 - diet deficient in protein or purines

8 - Wilson's disease 9 - hemochromatosis

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SEROLOGY / IMMUNOLOGY FORM 1 1 VDRL (Venereal Diagnosis Research Laboratory ) RPR (Rapid Plasma Reagin )
Normal range: Negative Positive test: Syphilis, other treponemal diseases (yaws, pinta, bejel) Note: A false-positive test may be seen in patients with systemic lupus erythematosus and other autoimmune diseases, infectious mononucleosis, HIV, atypical pneumonia, malaria, leprosy, typhus fever, rat-bite fever, relapsing fever.

2 - Treponemal pallidum particle agglutination (TPHA)

The Syphilis TPHA test is an indirect hemagglutination assay used for the detection and titration of antibodies against the causative agent of syphilis,Treponema pallidum subspecies pallidum.

3 - FTA-ABS (serum)
Normal: Nonreactive Reactive in: Syphilis, other treponemal diseases (yaws, pinta, bejel), SLE, pregnancy

4 - Rheumatoid Factor
It is detected in 70% of pt with RA. Not Diagnostic High titer in early RA Poor prognosis

Condition with positive RF :

A) Rheumatological diseases (% of cases) RA (70%) SLE (25%) Sjgerns syndrome (90%) Systemic sclerosis (30%)
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 Polymyositis / dermatomyositis (50%) Juvenile idiopathic arthritis (some cases) B) Viral Infections: Viral hepatitis Infectious mononucleosis C) Chronic Infections: TB Infective endocarditis D) Hyperglobulinaemias: Chronic liver disease Sarcoidosis Cryoglobulinaemia E) Normal population: Elderly Relatives of patients with RA Leprosy Syphilis

When to order: Should be ordered to confirm the diagnosis in patients

with inflammatory polyarthritis. Not useful for evaluating the course of the illness N.B : RF is not sensitive nor specific enough to rule in or out rheumatoid arthritis. . It is most useful as a prognostic indicator in patients with RA.

5 - Erythrocyte sedimentation rate (ESR) C-Reactive Protein (CRP)

ESR : Normal ranges (upper limits) 1750 years : Men10mm/h & Women 12mm/h 5160 Years : Men 12 & women 19, 60 : men 14 & women 20 Children: Newborn: 0 to 2 mm/hr. & Neonatal to puberty: 3 to 13 mm/hr High ESR (significant*look for a cause) 1- Any inflammatory disorder, e.g.

36

infection, rheumatoid. 2- TB. 3- Myocardial infarction (the ESR as an early response). 4- Anaemia N.B : An ESR of 30 probably means little but if >100 is highly significant and indicates something seriously wrong. & A normal ESR does not exclude organic disease. Golden Rule : When an increased rate is encountered with no Obvious clinical explanation, the physician should repeat the test after an appropriate interval rather than an exhaustive search for Occult disease . CRP vs ESR : CRP rises quickly after an inflammatory event and returns to normal within a week while the ESR rises slowly in response to increasing production of fibrinogen by the liver and falls slowly as well. CRP correlates better with disease course CRP is not affected by age. When is CRP ordered? When acute inflammation is a risk (such as from an infection after surgery) or suspected based on patient symptoms. It is also ordered to help evaluate conditions, such as RA and SLE What does the test result mean? In a healthy person, CRP is usually less than 10 mg/L. Most infections and inflammations result in CRP levels above 100 mg/L. A high or increasing amount of CRP in blood suggests acute infection & inflammation. If the CRP level in blood drops, it means that inflammation is being reduced. When results fall below 10 mg/L, Patient no longer has clinically active inflammation.

37

6 - Anti-streptolysin O titer ASO

The antibody level appears early following streptococcal infection. The titer level rises rapidly by 3-4 weeks and then declines quickly. The antibody level may remain raised for months. Levels greater than 200 units/ml are considered significant Diseases Involved (Rheumatic fever - Post streptococcal glomerulonephritis - Scarlet fever Erysipelas )

7 BRUCELLA (Abortus & Melitensis)

Serologic examination often provides the only positive laboratory findings in brucllosis. In acute infection, IgM antibodies appear early and are followed by IgG and IgA. The majority of patients have detectable agglutinins at this stage. As the disease progresses, IgM levels decline, and the avidity and subclass distribution of IgG and IgA change. The result is reduced or undetectable agglutinin titers. However, the antibodies are detectable by alternative tests, including the complement fixation test, Coombs' antiglobulin test, and enzyme-linked immunosorbent assay. There is no clear cutoff value for a diagnostic titer. Rather, serology results must be interpreted in the context of exposure history and clinical presentation. In endemic areas or in settings of potential occupational exposure, agglutinin titers of 1:3201:640 or higher are considered diagnostic; in nonendemic areas, a titer of 1:160 is considered significant. Repetition of tests after 24 weeks may demonstrate a rising titer.

8 WIDAL TEST
Widal test is a tube agglutination test employed in the serological diagnosis of enteric fever

Interpretation of widal test:

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Timing of test is important, as antibodies begin to arise during end of first week. The titres increase during second, third and fourth week after which it gradually declines. The test may be negative in early part of first week. Single test is usually of not much value. A rise in titre between two sera specimens is more meaningful than a single test. If the first sample is taken late in the disease, a rise in titre may not be demonstrable. Instead, there may be a fall in titre. Baseline titre of the population must be known before attaching significance to the titres. The antibody levels of individuals in a population of a given area give the baseline titre. A titre of100 or more for O antigen is considered significant and a titre in excess of 200 for H antigens is considered significant. Patients already treated with antibiotics may not show any rise in titre, instead there may be fall in titre. Patients treated with antibiotics in the early stages may not give positive results. Patients who have received vaccines against Salmonella may give false positive reactions. This can be differentiated from true infection by repeating the test after a week. True untreated infection results in rise in titre whereas vaccinated individuals dont demonstrate any rise in titre. Those individuals, who had suffered from enteric fever in the past, sometimes develop anti-Salmonella antibodies during an unrelated or closely related infection. This is termed anamnestic response and can be differentiated from true infection by lack of any rise in titre on repetition after a week. Antigen suspensions with fimbrial antigens may sometimes give false positive reactions due to sharing of fimbrial antigens by some Enterobacteriaceae members. Antigen suspension must be devoid of fimbrial antigens.

9 AMOEBIASIS 10 SCHISTOSOMIASIS
Stool samples can be examined microscopically for parasite eggs (S. mansoni or S. japonicum) or urine (S. haematobium). The eggs tend to be passed intermittently and in small amounts and may not be detected, so it may be necessary to perform a blood (serologic) test.
39

11 LEISHMANIASIS
Leishmaniasis is diagnosed in the haematology laboratory by direct visualization of the amastigotes (Leishman-Donovan bodies).

12 - Chlamydia Group Antibody

Negative: _0.91; Equivocal: 0.911.09; Positive: _1.10 Used in the diagnosis of chlamydial infection. Detects IgG antibodies to C. trachomatis, C. pneumoniae, and C. psittaci.

13 - Helicobacter pylori Antibody Titers

Normal : Negative

Organism associated with gastic ulcer and gastritis. Also may be assessed by culture, biopsy, or breath test limited by its inability to distinguish between current, active infection, and prior infection that has resolved.

14 - Anti-nuclear Antibodies ANAs

Are detected in many autoimmune disease. ANA is used as a screening test for SLE. Low titre occur in RA and chronic infections. Can also occur in normal individuals, especially elderly.

15 Antimitochondrial Antibody (AMA)

The AMA test is ordered to help diagnose primary biliary cirrhosis (PBC). Levels of AMA may be lower in children and in those with compromised immune systems. The level of AMA is not related to the severity of PBC symptoms or to a

40

patients prognosis.

16 Anti-Smooth Muscle Antibody (ASMA)

o help diagnose chronic active autoimmune hepatitis and distinguish it from other causes of liver injury

17 - Anticytoplasmic Autoantibodies(ANCA)
An ANCA test is ordered to evaluate someone who has symptoms that may be due to autoimmune vasculitis.

18 - Anti-double stranded DNA-Ab dsDNA

They are diagnostic of active SLE. May be negative in mild or inactive SLE. High titres of IgG anti-dsDNA indicate a poor prognosis and are specific to SLE. Anti-single stranded DNA antibodies are non-specific.

19 - ANTICARDIOLIPIN ANTIBODY (ACA)

Normal range: Negative: Test includes detection of IgG, IgM, and IgA antibody to phospholipid, cardiolipin Present in: Antiphospholipid antibody syndrome, chronic hepatitis C

20 THYROID HORMONES
1 - T3 (triiodothyronine) Normal range: 75-220 ng/dl (1.2-3.4 nmol/L Abnormal values: A. B. Elevated in hyperthyroidism (usually earlier and to a greater extent than serum T4). Useful in diagnosing: 1. T3 hyperthyroidism (thyrotoxicosis): increased T3, normal FTI.
41

2. 3. 4.

Toxic nodular goiter: increased T3, normal or increased T4. Iodine deficiency: normal T3, possibly decreased T4. Thyroid replacement therapy with liothyronine (Cytomel): normal T4, increased T3 if patient is symptomatically hyperthyroid.

Not ordered routinely but indicated when hyperthyroidism is suspected and serum free T4 or FTI inconclusive. 2 - T4, FREE (free thyroxine) Normal range: 0.8-2.8 ng/dl Elevated in: Graves' disease, toxic multinodular goiter, toxic adenoma, iatrogenic and factitious causes, transient hyperthyroidism
3 - THYROID-STIMULATING HORMONE (TSH) Normal range: 2-11 U/ml (2-11 mU/L [CF: 1; SMI: 1 mU/L])

Conditions That Increase Serum Thyroid-Stimulating Hormone Values

1 - Laboratory error insufficient dose 2 - Primary hypothyroidism 3 - Synthroid therapy with

4 - Lithium or amiodarone; some patients 5 - Hashimoto's thyroiditis in later stage 6 - Large doses of inorganic iodide (e.g., SSKI) 7 - Severe nonthyroid illness in recovery phase 8 - Iodine deficiency (moderate or severe) 9 - Addison's disease

10 - TSH specimen drawn in evening (peak of diurnal variation) 11 - Pituitary TSHsecreting tumor 12 - Therapy of hypothyroidism (3-6 wk after beginning therapy [range, 1-8 wk]; sometimes longer when pretherapy TSH is over 100 U/ml) 13 - Acute psychiatric illness 14 - Peripheral resistance to T4 syndrome
42

15 Amphetamines

16 - High altitudes

Conditions That Decrease Serum Thyroid-Stimulating Hormone Values 1 - Laboratory error 2 - T4/T3 toxicosis (diffuse or nodular etiology) 3 - Excessive therapy for hypothyroidism 4 - Active thyroiditis (subacute, painless, or early active Hashimoto's disease) 5 - Multinodular goiter containing areas of autonomy 6 - Severe nonthyroid illness (especially acute trauma, dopamine, or glucocorticoid) 7 - T3 toxicosis 8 - Pituitary insufficiency 9 - Cushing's syndrome (and some patients on high-dose glucocorticoid) 10 - Thyroid-stimulating hormone drawn 2-4 hr after levothyroxine dose 11 - Postpartum transient toxicosis 12 - Factitious hyperthyroidism

13 - Radioimmunoassay, surgery, or antithyroid drug therapy for hyperthyroidism 4-6 wk (range 2 wk2 yr) after the treatment 14 - Hyperemesis gravidarum 15 - Amiodarone therapy

SEROLOGY / IMMUNOLOGY FORM 2

1 - HEPATITIS A ANTIBODY
Normal: Negative Present in: Viral hepatitis A; can be IgM or IgG (if IgM, acute hepatitis A; if IgG, previous infection with hepatitis A)

2 - HAV-IGM ANTIBODY
Appearance About the same time as clinical symptoms (3-4 wk after exposure, range 14-60

43

days), or just before beginning of AST/ALT elevation (range 10 days before7 days after) Peak About 3-4 wk after onset of symptoms (1-6 wk) Becomes Nondetectable 3-4 mo after onset of symptoms (1-6 mo). In a few cases HAV-IgM antibody can persist as long as 12-14 mo.

3 - HAV-TOTAL ANTIBODY
Appearance About 3 wk after IgM becomes detectable (therefore about the middle of clinical symptom period to early convalescence) Peak About 1-2 mo after onset Becomes Nondetectable Remains elevated for life, but can slowly fall somewhat

4 - HEPATITIS B SURFACE ANTIGEN (HBsAg)

Normal: Not detected Detected in: Acute viral hepatitis type B, chronic hepatitis B Appearance 2-6 wk after exposure (range 6 days6 mo); 5%-15% of patients are negative at onset of jaundice Peak 1-2 wk before to 1-2 wk after onset of symptoms Becomes Nondetectable 1-3 mo after peak (range 1 wk-5 mo)
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N.B : HBSAg: shows current active HBV infection. Persistence over 6 mo indicates carrier/chronic HBV infection.

5 - HBS-Ab
HBSAb-total: shows previous healed HBV infection and evidence of immunity. HBCAb-IgM: shows either acute or very recent infection by HBV. In convalescent phase of acute HBV, may be elevated when HBSAg has disappeared (core window). Negative HBCAb-IgM with positive HBSAg suggests either very early acute HBV or carrier/chronic HBV. HBCAb-total: only useful to show past HBV infection if HBSAg and HBcAb-IgM are both negative.

6 - HBe -Ag
HBe-Ag: when present, especially without HBeAb, suggests increased patient infectivity. HBeAb-total: when present, suggests less patient infectivity. . HBSAg positive, HBCAb negative*About 5% (range 0%-17%) of patients with early-stage HBV acute infection (HBCAb rises later) HBSAg positive, HBCAb positive, HBSAb negative a. b. c. Most of the clinical symptom stage Chronic HBV carriers without evidence of liver disease (asymptomatic carriers) Chronic HBV hepatitis (chronic persistent type or chronic active type)

HBSAg negative, HBCAb positive,* HBSAb negative a. b. Late clinical symptom stage or early convalescence stage (core window) Chronic HBV infection with HBSAg below detection levels with current tests
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c.

Old previous HBV infection

HBSAg negative, HBCAb positive, HBSAb positive a. b. Late convalescence to complete recovery Old infection

7 - HEPATITIS C VIRAL INFECTION

HCV-Ag HCV nucleic acid probe: shows current infection by HCV (especially using PCR amplification). HCV -Ab HCV-Ab (IgG): current, convalescent, or old HCV infection.

8 - DELTA HEPATITIS COINFECTION

(ACUTE HDV + ACUTE HBV)

OR SUPERINFECTION
(ACUTE HDV + CHRONIC HBV)

HDV
HDV-Ag HDV-Ag: shows current infection (acute or chronic) by HDV. HDV-Ab HDV-Ab (IgM): high elevation in acute HDV; does not persist. Low or moderate elevation in convalescent HDV; does not persist. Low to high persistent elevation in chronic HDV (depends on degree of cell injury and sensitivity of the assay). HDV-Ab (total): high elevation in acute HDV; does not persist. High persistent elevation in chronic HDV.
46

HDV-AG Detected by DNA probe, less often by immunoassay Appearance: Prodromal stage (before symptoms); just at or after initial rise in ALT (about a week after appearance of HBSAg and about the time HBCAb-IgM level begins to rise) Peak: 2-3 days after onset Becomes nondetectable: 1-4 days (may persist until shortly after symptoms appear) HDV-AB (IGM) Appearance: about 10 days after symptoms begin (range 1-28 days) Peak: about 2 wk after first detection Becomes nondetectable: about 35 days (range 10-80 days) after first detection (most other IgM antibodies take 3-6 mo to become nondetectable) HDV-AB (TOTAL) Appearance: about 50 days after symptoms begin (range 14-80 days); about 5 wk after HDV-Ag (range 3-11 wk) Peak: About 2 wk after first detection Becomes nondetectable: about 7 mo after first detection (range 4-14 mo)

9 - HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY, type 1

(HIV-1)
Normal range: Not detected Abnormal result: HIV antibodies usually appear in the blood 1-4 mo after infection.

10 - Human T-cell Lymphotropic Virus Type 1 (HTLV-I)

A virus that has been seriously implicated in several kinds of diseases including HTLV-I-associated myelopathy, Strongyloides stercoralis hyper-infection, and a virus cancer link for leukemia .Between one in twenty and one in twenty-five
47

infected persons are thought to develop cancer as a result of the virus

11 Herpes simplex virus 1 and 2 (HSV) 12 - Cytomegalovirus (CMV) Antibodies

IgM 1:8; IgG 1:16 CMV is a virus in the herpes family. Active infection significant in pregnant women, potential.transplant patients and immunocompromised patients. If active infection is suspected, a second sample is assessed in 1014 days.

13 - TORCH Screen (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes Viruses)

Negative Detect maternal and infant infection. High levels of immunoglobulin IgM against any of the microorganisms indicates congenital infection

Full urine examination

Macroscopic (physical + chemical) Microscopic (Urine sediments) 10-15 ml's may be required for urinalysis What can a urinalysis show? to diagnose : UTI or kidney infection, to evaluate causes of kidney failure, to screen for progression of some chronic conditions such as DM and HTN. N.B : Anuria : < 100 ml/24h Oliguria : 100-500 ml/24h
48

What is macroscopic urinalysis? A - Measuring the pH pH and crystalline deposits Determination of the pH of urine is useful for the identification of crystalline Deposits. Some crystals are deposited only in acid urine, others only in alkaline urine For example: acid urine: oxalates, uric acid alkaline urine: phosphates, carbonates, ammonium B - specific gravity : very important because the number indicates whether the pt is hydrated or dehydrated. If the specific gravity is under 1.007, pt is hydrated. If is above 1.010, pt is dehydrated. If sp gr is not > 1.022 after a 12-hour deprivation: generalized renal impairment nephrogenic diabetes insipidus. sp gr tends to be 1.007 to 1.010 in ESRD. Any urine having a sp gr > 1.035 is either: contaminated contains very high levels of glucose patient received high density radio-opaque dyes or low molecular weight dextran solutions. C - Protein: Normal total protein excretion < 150 mg/24 hours or 10 mg/100 ml in any random single specimen.
49

Proteinuria : >150 mg/day. If > 3.5 gm/24 hours = severe = nephrotic syndrome. Trace =10 mg/100 ml or 150 mg/24 hours (upper limit of normal). 1+ = 200-500 mg/24 hours 2+ = 0.5-1.5 gm/24 hours 3+ = 2-5 gm/24 hours 4+ >7 gm/24 hours N.B : Protein/Creatinine Ratio (PCR) : a better test than 24 hour urinary protein measurement. nephrotic syndrome being for PCR > 100 mg/mmol. D - Glucose : Normally,< 0.1% (< 130 mg/24 hr) generally means diabetes mellitus. E - Ketones: Ketones (acetone, aceotacetic acid, beta-hydroxy-butyric acid) resulting from either diabetic ketosis or calorie deprivation. F - Nitrite: If positive, indicates that bacteria may be present in significant numbers in urine. Gram negative rods such as E. coli are more likely. G - Leukocyte Esterase: If positive= presence of WBCs (whole or lysed) ie Pyuria. A negative leukocyte esterase test means that an infection is unlikely and that, without additional evidence of urinary tract infection, microscopic exam and/or urine culture need not be done to rule out significant bacteriuria. What is microscopic urinalysis? A - Red Blood Cells: Hematuria = RBCs (>1/HPF) in urine sediment. Causes: Glomerular damage, Tumors eroding the UT, Kidney trauma, Urinary tract stones, Physical stress N.B : RBCs may also contaminate the urine from: vagina in menstruating
50

women or trauma (bladder catherization). B - White Blood Cells (Pus cells) : presence of abnormal numbers (>2/HPF) of leukocytes. Usually, the WBC's are granulocytes. Causes Either upper or lower UTI , acute GN , acute Pyelonephritis Contamination sources include: Vaginal discharge (vaginal and cervical infections)& External urethral meatus in men and women. C - Epithelial Cells : Renal tubular epithelial cells and transitional cells (from the renal pelvis, ureter, or bladder) are rounded. Squamous epithelial cells from the skin surface or from the outer urethra can appear in urine and may indicate contamination of the specimen with skin flora. D Casts : are cylindrical structures produced by the kidney and present in the urine in certain disease states. They form in the distal convoluted tubule and collecting ducts of nephrons, then dislodge and pass into the urine, where they can be detected by microscopy. Hyaline Casts= can be seen even in healthy subjects RBcs casts= GN or severe tubular damage WBCs casts= acute pyelonephritis, but they may also be present with glomerulonephritis. Their presence indicates inflammation of the kidney, because such casts will not form except in the kidney. a waxy cast seen in end-stage chronic renal disease E Bacteria : multiply rapidly in urine standing at room temperature.
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N.B : If UTI is suspected request culture and colony count. Colony count >100,000/ml is significant. F Yeast : Most often they are Candida, which may colonize bladder, urethra, or vagina. G Crystals : Common crystals seen (even in healthy subjects) Calcium oxalate & phosphate

MULTIPURPOSE REQUISITION LIPASE (serum)

Normal range: 0-160 U/L (0-2.66 kat/L [CF: 0.01667; SMI: 0.02 kat/L]) Elevated in: Acute pancreatitis, perforated peptic ulcer, carcinoma of pancreas (early stage), pancreatic duct obstruction, bowel infarction, intestinal obstruction

RENIN (serum)
ELEVATED IN: Drugs (thiazides, estrogen, minoxidil), chronic renal failure, Bartter's syndrome, pregnancy (normal), pheochromocytoma, renal hypertension, reduced plasma volume, secondary aldosteronism Decreased in: Adrenocortical hypertension, increased plasma volume, primary aldosteronism, drugs (propranolol, reserpine, clonidine)

PROSTATE-SPECIFIC ANTIGEN (PSA)

Normal range: 0-4 ng/ml Age-Specific Reference Ranges for PSA SERUM PSA (NG/ML) Age (yr) Whites Japanese African American 40-49 50-59 60-69 0-2.5 0-3.5 0-4.5 0-2.0 0-3.0 0-4.0 0-2.0 0-4.0 0-4.5
52

SERUM PSA (NG/ML) Age (yr) Whites Japanese African American 70-79 0-6.5 0-5.0 0-5.5

Elevated in: Benign prostatic hypertrophy, carcinoma of prostate, postrectal examination, prostate trauma D-dimers : produced during polymerisation of fibrinogen as it forms fibrin. a sensitive indicator of coagulation activation D-dimers seen in : 1) DIC. 2) DVT. 3) PE.( Pulmonary Embolism )

N.B : AMA ( Anti-Mitochondrial-Antibody ) >95% of pt 1ry Biliary Cirrhosis ANCA ( antineutrophil cytoplasmic antibody ) in 1ry sclerosing Cholangitis & Vasculitis

Glycated Hemoglobin (HbA1c)

Sometimes incorrectly referred to as "glycosylated hemoglobin test. Important blood test used to determine how well the diabetes is being controlled. The test provides an average of blood glucose measurements over the past 3 months (120 days) but mostly the last 6 8 weeks. Normal range = 4%-6%. The goal for people with diabetes is an HbA1c < 7%. The higher the HbA1c, the higher the risks of developing complications related to A one percent point reduction in HbA1c is associated with 35 % reduction in microvascular disease CLINICAL PRACTICE RECOMMENDATIONS FOR DIABETES DIAGNOSIS An HA1c score of 5.7% to 6.4% indicates pre-diabetes, and
53

An HA1c level of 6.5% or higher indicates the presence of diabetes. Categories suggesting an increased risk for future diabetes now include an HA1c range of 5.7% to 6.4%, as well as impaired fasting glucose and impaired glucose tolerance levels.

HUMAN CHORIONIC GONADOTROPIN (hCG)

Normal range: Varies with gestational stage 1st week: 10-50 mU/ml 1-2 wk: 40-300 mU/ml 2-3 wk: 100 - 1000 mU/ml 3-4 wk: 500 - 6000 mU/ml 4-5 wk: 1500 - 23000 mU/ml 5 6 weeks: 2400-135000 mU/ml 6 7 weeks : 10500 161000 7 8 weeks : 18000 209000 8 9 weeks : 37500 218000 9 10 weeks : 33700 218700 10 11 weeks : 42800 219000 13 14 weeks : 15400 190000 2nd T : 4500 114400 3rd T : 3500 - 800000 Elevated in: Normal pregnancy, hydatidiform mole, choriocarcinoma, germ cell tumors of testicle, some nontrophoblastic neoplasms (e.g., neoplasms of cervix, gastrointestinal tract, ovary, lung, breast)

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FOLLICLE-STIMULATING HORMONE (FSH)

Normal range: 5-20 mIU/ml Elevated in: Menopause, primary gonadal failure, alcoholism, castration, Klinefelter's syndrome, gonadotropin-secreting pituitary hormones Decreased in: Pregnancy, polycystic ovary disease, anorexia nervosa, anterior pituitary hypofunction

LUTEINIZING HORMONE
Normal range: 5-25 mIU/ml Elevated in: Postmenopause, pituitary adenoma, primary gonadal dysfunction, polycystic ovary syndrome Decreased in: Severe illness, anorexia nervosa, malnutrition, pituitary or hypothalamic impairment, severe stress

PROLACTIN
Normal range: <20 ng/ml Elevated in: Prolactinomas (level >200 highly suggestive), drugs (phenothiazines, cimetidine, tricyclic antidepressants, metoclopramide, estrogens, antihypertensives [methyldopa], verapamil, haloperidol), postpartum, stress, hypoglycemia, hypothyroidism

TESTOSTERONE (total testosterone)

Normal range: (Variable with age and sex) Serum/plasma: Males: 280-1100 ng/dl Females: 15-70 ng/dl Urine: Males: 50-135 g/day Females: 2-12g/day Elevated in: Testicular tumors, ovarian masculinizing tumors Decreased in: Hypogonadism
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ESTROGEN
Normal range: Serum: Males: 20-80 pg/ml Luteal: 160-400 pg/ml Postmenopausal: <130 pg/ml Urine: Males: 4-23 g/g creatinine Midcycle: 32-104 g/g creatinine Luteal: 8-135 g/g creatinine Elevated in: Hyperplasia of adrenal cortex, ovarian tumors producing estrogen, granulosa and thecal cell tumors, testicular tumors Decreased in: Menopause, hypopituitarism, primary ovarian malfunction, anorexia nervosa, hypofunction of adrenal cortex, ovarian agenesis, psychogenic stress, gonadotropin-releasing hormone deficiency Females: Follicular: 7-65 g/g creatinine

Females: Follicular: 60-200 pg/ml

ANION GAP
Normal range: 9-14 mEq/L Elevated in: Lactic acidosis, ketoacidosis (diabetes, alcoholic starvation), uremia (chronic renal failure), ingestion of toxins (paraldehyde, methanol, salicylates, ethylene glycol), hyperosmolar nonketotic coma, antibiotics (carbenicillin) Decreased in: Hypoalbuminemia, severe hypermagnesemia, IgG myeloma, lithium toxicity, laboratory error (falsely decreased sodium or overestimation of bicarbonate or chloride), hypercalcemia of parathyroid origin, antibiotics (e.g., polymyxin)

ARTERIAL BLOOD GASES

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Normal range: Po2: 75-100 mm Hg Pco2: 35-45 mm Hg HCO3: 24-28 mEq/L pH: 7.35-7.45 Abnormal values: Acid-base disturbances

CLOSTRIDIUM DIFFICILE TOXIN ASSAY (stool)

Normal: Negative Detected in: Antibiotic-associated diarrhea and pseudomembranous colitis

COMPLEMENT
Normal range: C3: 70-160 mg/dl &C4: 20-40 mg/dl Abnormal values: Decreased C3: Active SLE, immune complex disease, acute glomerulonephritis, inborn C3 deficiency, membranoproliferative glomerulonephritis, infective endocarditis, serum sickness, autoimmune/chronic active hepatitis Decreased C4: Immune complex disease, active SLE, infective endocarditis, inborn C4 deficiency, hereditary angioedema, hypergammaglobulinemic states, cryobulinemic vasculitis

CORTISOL, PLASMA
Normal range: Varies with time of collection (circadian variation): 8 am: 4-19 g/dl (110-520 nmol/L 4 pm: 2-15 g/dl (50-410 nmol/L Elevated in: Ectopic adrenocorticotropic hormone production (i.e., oat cell carcinoma of lung), loss of normal diurnal variation, pregnancy, chronic renal

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failure iatrogenic, stress, adrenal, or pituitary hyperplasia or adenomas Decreased in: Primary adrenocortical insufficiency, anterior pituitary hypofunction, secondary adrenocortical insufficiency, adrenogenital syndromes

C-PEPTIDE
Elevated in: Insulinoma, sulfonylurea administration Decreased in: Insulin-dependent diabetes mellitus, factitious insulin administration

-1 FETOPROTEIN
Normal range: 0-20 ng/ml (0-20 g/L [CF: 1; SMI: 1 g/L]) Elevated in: Hepatocellular carcinoma (usually values >1000 ng/ml), germinal neoplasms (testis, ovary, mediastinum, retroperitoneum), liver disease (alcoholic cirrhosis, acute hepatitis, chronic active hepatitis), fetal anencephaly, spina bifida, basal cell carcinoma, breast carcinoma, pancreatic carcinoma, gastric carcinoma, retinoblastoma, esophageal atresia

GLUCOSE-6-PHOSPHATE DEHYDROGENASE SCREEN

Normal: G6PD enzyme activity detected Abnormal: If a deficiency is detected, quantitation of G6PD is necessary; a G6PD screen may be falsely interpreted as normal after an episode of hemolysis because most G6PD-deficient cells have been destroyed.

HELICOBACTER PYLORI (serology, stool antigen)

Normal range: Not detected Detected in: H. pylori infection. Positive serology can indicate current or past infection. Positive stool antigen test indicates acute infection (sensitivity and specificity >90%). Stool testing should be delayed at least 4 weeks after eradication therapy.
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INSULIN-LIKE GROWTH FACTOR-1 (IGF-1), serum

Normal range: Age 16-24: 182-780 ng/ml Age 25-39: 114-492 ng/ml Age 40-54: 90-360 ng/ml Age>55: 71-290 ng/ml Elevated in: Adolescence, acromegaly, pregnancy, precocious puberty, obesity Decreased in: Malnutrition, delayed puberty, diabetes mellitus, hypopituitarism, cirrhosis, old age

SEMEN ANALYSIS
Semen Analysis Reference Ranges Color Grayish white pH Volume Sperm count Motility % Normal sperm Viscosity 7.3-7.8 (literature range, 7.0-7.8) 2.0-5-0 ml (literature range, 1.5-6.0 ml) 20-250 million/ml (literature range for upper limit varies from 100-250 million/ml) >60% motile <3 hours after specimen is obtained (literature range, >40% to >70%) >60% (literature range, >60% to >70%) Can be poured from a pipet in droplets rather than a thick strand

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