Clinical Chemistry Flashcards by Aubs Ganda

concerned with diagnosing and monitoring disease by measuring the concentration of
chemicals, principally in blood plasma and urine.

Clinical chemistry

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chemical analysis of feces and other body fluids

Clinical chemistry

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-first to make the true connection between chemistry and medical practice
-He was a vitalist
- application of chemistry to physiology in the treatment of disease
-Favored the study of physics and chemistry by medical students

William Prout

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-Urged the medical school curriculum to include first-rate instruction in English
- “Medical men would be much better served if they spent some time in acquiring knowledge about chemistry and physics instead of learning sore Latin and Greek.”

Henry Bence Jones

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-“Chemical studies are relevant to clinical medicine.”
-Continuous exchange between the solid parts and blood. “It is in the blood that we must look for many important modifications in connection with disease.”

Thomas Hodgkin

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Recognizing the powerful aid that the science of medicine “has received from the study of
organic chemistry and the knowledge and use of the microscope,” authorized the purchase of a microscope at a cost

Massachusetts General Hospital
1847

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Established the position of “Chemist-Microscopist” To cope with the growing number of chemical tests, the physician would usually enlist the help of chemists or physicians skilled in chemistry

Massachusetts General Hospital
1851

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Proposed that American hospitals employ clinical chemists to advance their ability to differentiate
between the physiologic and the pathologic

Otto Knut Folin

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Chemistry In Medical Education

William Prout
Henry Bence Jones
Thomas Hodgkin
Massachusetts General Hospital
Otto Knut Folin

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-Determined reference intervals
-Correlated variations with pathologic conditions
-Elucidated metabolic pathways in health and disease

Otto Knut Folin and Donald Dexter Van Slyke

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Invented a volumetric gas-measuring apparatus for the determination of CO2 concentration

Donald Dexter Van Slyke

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-Together with Hsien Wu, they made a method for the production of a protein-
free filtrate that can be used for determining blood sugar.
-He also developed the Duboscq-type colorimeter for the measurement of creatinine in urine

Otto Knut Folin

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Developed the alkaline pirate method for the determination of creatinine concentration

Max Jaffe

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Clinical Chemistry in Laboratory Diagnosis

Otto Knut Folin and Donald Dexter Van Slyke
Max Jaffe

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-Observation of the intensity of colored product after chemical reactions
-Pioneered by Folin after the development of the Duboscq-type visual colorimeter

Colorimetry

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-Measurement of light intensity at selected wavelengths
-Initiated by the development of the Beckman DU Spectrophotometer by Cary and Beckman

Spectrophotometry

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Continuous-flow instrument that reacted specimens and reagents to produce a
measurable color density

AutoAnalyzer

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-Introduced by Norman Anderson
-Second attempt towards automation; First clinical analyzer to incorporate a computer

Centrifugal analyzer

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Capable of performing multiple tests analyzed
one after another on a given clinical specimen

Sequential Multiple Analyzer with Computer (SMAC)

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Introduced the perfected technology of automated pipetting, which is the approach of
choice for automation in clinical chemistry laboratories even up to these days.

Beckman Astra

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Early Instrumentation in Clinical Chemistry

Colorimetry
Spectrophotometry
AutoAnalyzer
Centrifugal analyzer
Sequential Multiple Analyzer with Computer (SMAC)
Beckman Astra

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Laboratory Methods

Photometric methods
Chromatography
Other analytic techniques

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Photometric methods

Spectrophotometry
Atomic absorption spectrophotometry
Fluorometry
Chemiluminescence
Turbidimetry
Nephelometry

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Chromatography

Thin-layer chromatography (TLC)
High-performance liquid chromatography (HPLC)
Gas chromatography (GC)

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Other analytic techniques

lon-selective electrodes Osmoretry Electrophoresis

-A chemical reaction produces a colored substance that absorbs light of a specific wavelength -The amount of light absorbed is directly proportional to the concentration of the analyte

Spectrophotometry

Measures light absorbed by ground-state atoms

Atomic absorption spectrophotometry

Atoms absorb light of a specific wavelength and emit light of a longer wavelength

Fluorometry

A chemical reaction that produces light Usually involves the oxidation of luminol, acridinium esters, or dioxetanes

Chemiluminescence

Measures reduction in light transmission by particles in suspension

Turbidimetry

Similar to turbidity, but the light is measured at an angle from a light source

Nephelometry

Screening test for drugs of abuse in urine

Thin-layer chromatography (TLC)

Separation of thermolabile compounds

High-performance liquid chromatography (HPLC)

Separation of volatile compounds or compounds that can be made volatile

Gas chromatography (GC)

The potential difference between two electrodes directly related to concentration of analyte

lon-selective electrodes

Determines osmolality (i.e., measurement of number of dissolved particles in solution, irrespective of molecular weight, size, density, or type) based on freezing-point depression

Osmoretry

Electrophoresis

-Separation of charged particles in an electrical field -Anions move to positively charged pole; cations to negatively charged pole -The greater the charge, the faster the migration

Glucose, fasting NV

70-99 mg/dL

Cholesterol, total NV

<200 mg/dL

HDL cholesterol NV

60 mg/dL

LDL cholesterol NV

Optimal: <100 mg/dL

Triglycerides NV

Desirable: <150 mg/dL

Total protein NV

6.4-8.3 g/dL

Albumin NV

3.5-5 g/dL

Microalbumin (ON URINE) NV

50-200 mg/24 hour + in diabetics at risk of nephropathy

Carbohydrates, Lipids and Proteins Analytes

Glucose, fasting Cholesterol, total HDL cholesterol LDL cholesterol Triglycerides Total protein Albumin Microalbumin

high glucose, fasting

diabetes mellitus, other endocrine disorders, acute stress, pancreatitis

low glucose, fasting

insulinoma, insulin-induced hypoglycemia, hypopituitarism

clinical significance in cholesterol

-Limited value for predicting risk of coronary artery disease (CAD) by itself -Used in conjunction with high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol

clinical significance in HDL cholesterol

Appears to be inversely related to CAD

clinical significance in LDL cholesterol

Risk factor for CAD

clinical significance in triglycerides

Risk factor for CAD

high protein

dehydration, chronic inflammation, multiple myeloma

low protein

nephrotic syndrome, malabsorption, overhydration, hepatic insufficiency, malnutrition, agammaglobulinemia

high albumin

dehydration

low albumin

malnutrition, liver disease, nephrotic syndrome, chronic inflammation

high microalbumin or urine

diabetics at risk of nephropathy

Blood Urea Nitrogen (BUN) NV

8-26 mg/dL

Creatinine NV

0.7-1.5 mg/dL

Uric acid NV

Male 3.5-7.2 mg/dL Female: 2.6-6 mg/dL

Ammonia NV

19-60 ug/dL

Nonprotein Nitrogen compounds

Blood Urea Nitrogen (BUN) Creatinine Uric acid Ammonia

high BUN

kidney disease

low BUN

overhydration or liver disease

high creatinine

kidney disease

high uric acid

gout, renal failure, ketoacidosis, lactate excess, high nucleoprotein diet, leukemia, lymphoma, polycythemia

low uric acid

administration of ACTH, renal tubular defects

high ammonia

liver disease, hepatic cora, renal failure, Reye's syndrome

Sodium NV

136-145 mmolL

Potassium NV

3.5-5.1 mmol/L

Chloride NV

98-107 mmol/L

CO2, total NV

23-29 mmol/L

Major electrolytes analytes

Sodium Potassium Chloride CO2, total

sodium is high due to

high intake or IV administration, hyperaldosteronism, excessive sweating, burns, diabetes insipidus

sodium is low due to

renal or extrarenal loss (vomiting, diarrhea, sweating, burns) or high extracellular fluid volume

potassium is high due

high intake, low excretion, crush injuries, metabolic acidosis

potassium is low due to

high Gl or urinary loss, use of diuretics, metabolic alkalosis

chloride is high due to

same conditions as high NA excess loss of HCO3

chloride is low from

prolonged vomiting, diabetic ketoacidosis, aldosterone deficiency, salt-losing renal diseases, metabolic alkalosis, compensated respiratory acidosis

high CO2

metabolic alkalosis, compensated respiratory acidosis

low CO2

metabolic acidosis, compensated respiratory alkalosis

Magnesium NV

1.6-2.6 mg/dL

Calcium NV

Total: 8.6-10 mg/dL lonized: 4.60-5.08 mg/dL

Phosphorus, inorganic (phosphate) NV

2.5-4.5 mg/dL

Lactate (lactic acid)

4.5-19.8 mg/dL

Other electrolytes

Magnesium Calcium Phosphorus, inorganic (phosphate Lactate (lactic acid)

high magnesium is due to

due to renal failure, high intake (e.g., antacids), dehydration, bone cancer, endocrine disorders

low magnesium is due to

severe illness, Gl disorders, endocrine disorders, renal loss

calcium is high with

primary hyperparathyroidism, cancer, multiple myeloma.

calcium is low with

hypoparathyroidism, malabsorption, vitamin D deficiency, renal tubular acidosis

phosphate is high with

with renal disease, and hypoparathyroidism.

phosphate is low with

with hyperparathyroidism, vitamin D deficiency, renal tubular acidosis

clinical significance lactate

sign of lowered O2 to tissues

iron NV

Male: 65-175 Female: 50-170 ug/dL

Transferrin

200-360 mg/dL

Ferritin

Male: 20-250 Female: 10-120 ug/L

iron analytes

Iron Transferrin Ferritin

iron is high with

with iron overdose, hemochromatosis, sideroblastic anemia, hemolytic anemia, liver disease

iron is low with

iron deficiency anemia

transferrin is high with

iron deficiency anemia

transferrin is low with

iron overdose, hemochromatosis, chronic infections, malignancies

high ferritin

iron overload, hemochromatosis, chronic infections, malignancies

low ferritin

low deficiency anemia

Acid phosphatase (ACP) tissue

Prostate

Alkaline phosphatase (ALP) tissue

Almost all

Aspartate aminotransferase (AST) tissue

Many Highest in liver, heart, and skeletal muscle

Alanine aminotransferase (ALT) tissue

Liver, RBCs

Gamma-glutamyl transferase (GGT) tissue

Liver, kidneys, pancreas

Lactate dehydrogenase (LD) tissue

All, Highest in liver, heart, anemia skeletal muscle, RBCs

Creatine kinase (CK) tissue

Cardiac muscle, skeletal muscle, brain

Amylase (AMS) tissue

Salivary glands, pancreas

Lipase (LPS)

Pancreas

Glucose-6-phosphate dehydrogenase (G6PD)

RBCS

Enzymes of clinical significance

Acid phosphate (ACP) Alkaline phosphate (ALP) Alanine aminotransferase (AST) Alanine aminotransferase (ALT) Gamma-glutamyl transferase (GGT) Lactate dehydrogenase (LD) Creatine kinase (CK) Amylase (AMS) Lipase (LPS) Glucose-6-phosphate-dehydrogenase (G6PD)

high prostate cancer

Acid phosphate (ACP)

liver and bone disease; levels higher in biliary tract obstruction than in hepatocellular disorders

Alkaline aminotransferase (AST)

high with liver disease (marked high with viral hepatitis), acute myocardial skeletal muscle infarction (AM), muscular dystrophy

Aspartate aminotransferase (AST)

high with liver disease

Alanine aminotransferase (ALT)

high in all hepatobiliary disorders, chronic alcoholism

Gamma-glutamyl transferase (GGT)

high with AMI, liver disease, pernicious anemia

Lactate dehydrogenase (LD)

high with AMI, muscular dystrophy

Creatine kinase (CK)

high in acute pancreatitis, other abdominal diseases, mumps

Amylase (AMS)

high in acute pancreatitis

Lipase (LPS)

Glucose-6-phosphate dehydrogenase (G6PD)

Inherited deficiency can lead to drug- induced hemolytic anemia

Cardiac Markers for Diagnosis of Acute Myocardial Infarction

Creatine kinase (CK-MB) Myoglobin Cardiac troponins (cTn)

Tests for Heart Failure

B-type natriuretic peptide (BNP)

Tests to Assess Risk of Coronary Artery Disease (CAD)

Cardiac C-reactive protein CRP (CRP) Total cholesterol

Released from the heart muscle of the left ventricle when fluid builds from heart failure

B-type natriuretic peptide

high with AMI, muscular dystrophy

Creatine kinase (CK

High-sensitivity CRP (hs-CRP) to ID individuals at risk of cardiovascular disease Best single biomarker for predicting cardiovascular events; test on two occasions because of individual variability

Cardiac C-reactive protein (cCRP)

Limited value for predicting the risk of CAD by itself Used in conjunction with HDL and LDL cholesterol

Total cholesterol

types of bilirubin

Total bilirubin conjugated (direct) bilirubin unconjugated (indirect) bilirubin

total bilirubin NV

0.2-1 mg/dL

conjugated bilirubin

<0.2 mg/dL

unconjugated bilirubin NV

<0.8 mg/dL

high in liver disease, hemolysis, and hemolytic disease of newborn In infants, >20 mg/dL is associated with brain damage

total bilirubin

liver disease, obstructive jaundice

conjugated bilirubin

prehepatic, posthepatic, and some types of bilirubin hepatic jaundice

unconjugated bilirubin

Enhances entry of glucose into cells Enhances storage of glucose as glycogen or conversion to fatty acids Suppresses breakdown of protein into amino acids, of adipose tissue into free fatty acids

insulin

Suppresses glucagon release from a cells Suppresses release of insulin, pituitary tropic hormones, gastrin and secretin

Somatostatin

Enhances release of glucose from glycogen Enhances synthesis of glucose from amino acids or fatty acids

Glucagon

Epinephrine

Adrenal medulla

Cortisol

Adrenal cortex

Adrenocorticotropic hormone (ACTH)

Anterior pituitary gland

Growth hormone

Anterior pituitary gland

Thyroxine

Thyroid

Enhances release of glucose from glycogen Enhances release of fatty acids from adipose tissues

epinephrine

Enhances synthesis of glucose from amino acids or fatty acids

cortisol

Enhances release of cortisol Enhances release of fatty acids from adipose tissue

Adrenocorticotropic hormone (ACTH)

Antagonizes insulin

growth hormone

Enhances release of glucose from glycogen Enhances absorption of sugars from intestine

thyroxine

The lowest concentration of drug in blood that will produce desired effect

Minimum effective concentration (MEC)

The lowest concentration of drug in blood that will produce an adverse response

Minimum toxic concentration (MC):

Salicylates, acetaminophen

Analgesics

Phenobarbital, phenytoin, valproic acid, carbamazepine, ethosuximide felbamate, gabapentin, lamotrigine

Antiepileptics

Methotrexate

Antineoplastics

Aminoglycosides (amikacin, gentamicin, kanamycin, tobramycin), vancomycin

Antibiotics

Digoxin, disopyramide, procainamide, quinidine

Cardioactives

Tricyclic antidepressants, lithium

Psychoactives

Cyclosporine, tacrolimus (FK-506)

Immunosuppressants

Amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, opiates, phencyclidine, tricyclic antidepressants

Drugs routinely tested for Drugs of Abuse