Clinical Chemistry Midterm Shortform PDF

# Clinical Chemistry ## **Carbohydrates** | Decreases glucose levels | | | ------------------------- | ------------------------ | | Insulin | Responsible for entry of glucose into cells. Increases glycogenesis. | | **Increases glucose levels** |...

# Clinical Chemistry ## **Carbohydrates** | Decreases glucose levels | | | ------------------------- | ------------------------ | | Insulin | Responsible for entry of glucose into cells. Increases glycogenesis. | | **Increases glucose levels** | | | Glucagon | Stimulates glycogenolysis and gluconeogenesis. Inhibits glycolysis. | | Cortisol | Insulin antagonist. Increases gluconeogenesis. | | Epinephrine | Promotes glycogenolysis and gluconeogenesis. | | Growth hormone | Insulin antagonist. | | Thyroxine | Increases glucose absorption from GI tract. Stimulates glycogenolysis. | ## **Diabetes Mellitus** | Type | Old Names | Cause | Characteristics | | ----------------------------- | ------------------------------ | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Type 1 | Type I | Beta cell destruction caused by autoimmune process. Absolute insulin deficiency. Genetic predisposition (HLA DR 3/4). | Acute onset. Most develop before age 25. Dependency on injected insulin. Prone to ketoacidosis and diabetic complications. | | Type 2 | Type II | Insulin resistance in peripheral tissue. Insulin secretory defect of beta cells. Associated with obesity. | Most common type. Onset usually after age 40. More common in women, Blacks, Hispanics, Native Americans. Not dependent on exogenous insulin. Not prone to ketoacidosis or diabetic complications. | | Gestational diabetes mellitus (GDM) | | Placental lactogen inhibits action of insulin. | Usually diagnosed during latter half of pregnancy. Some develop type 2 diabetes years later. Risk of intrauterine death or neonatal complications: macrosomia, hypoglycemia, hypocalcemia, polycythemia, hyperbilirubinemia. | ## **Tests for Diabetes Mellitus** | Test | Patient Preparation | Normal | Diabetes Mellitus | Comments | | --------------------------- | ------------------- | ------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Urine glucose | None | Negative | Positive | Not recommended for screening. False negatives in patients with elevated renal thresholds. 2-hour postprandial specimen is more sensitive. | | Random plasma glucose | None | 45-130 mg/dL | ≥200 mg/dL on two occasions, with symptoms of increased urination, thirst, and weight loss | Collected any time of day without regard to time since last meal. | | Fasting plasma glucose (FPG) | 8-12 hour fast | 70-110 mg/dL | ≥126 mg/dL on two occasions | FPG is recommended by the American Diabetes Association for screening and diagnosis, except during pregnancy. | | 2-hour post-prandial plasma glucose (2-hr PPG) | 75-g glucose load | 70-110 mg/dL | ≥200 mg/dL on two occasions. | | ## **Tests for Diabetes Mellitus Continued** | Test | Patient Preparation | Normal | Diabetes Mellitus | Comments | | --------------------------- | ------------------- | ------------------------------------------------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Oral glucose tolerance test (OGTT) | 8-12 hour fast. | Normal fasting, peak at 30 minutes (<200 mg/dL) return to baseline by 2 hours. | One value ≥200 mg/dL on two occasions. For gestational diabetes, two or more of the following venous plasma glucose values: Fasting ≥105 mg/dL 1-hour ≥190 mg.dL 2-hour ≥165 mg/dL 3-hour ≥145 mg/dL | Not very reproducible. American Diabetes Association says only baseline and 2-hour need to be determined, except during pregnancy. Check fasting level before giving glucose solution. If ↑ check with doctor before proceeding. | | O'Sullivan test for gestational diabetes | 50-g load of glucose | 1-hour plasma glucose <140 mg/dL | 1-hour plasma glucose ≥140 mg/dL | Screening test. If positive, follow-up with 3-hour OGTT using a 100-g glucose load. | | Glycohemoglobin (Hemoglobin A1c) | None. Fasting not required. | Therapeutic goal = 7% | >12% = poor control | Gives estimate of glucose control over previous 2–3 months. Specimen is whole blood (EDTA). Currently not used for diagnosis. | | Test | Patient Preparation | Normal | Diabetes Mellitus | Comments | | -------------- | ------------------- | --------------- | ------------------ | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | Fructosamine | None | 205–285 µmol/L | Increased | Glycated serum protein. Correlates with blood glucose level during past 1–3 weeks. | ## **Typical Laboratory Findings in Uncontrolled Diabetes Mellitus** - ↑ Blood glucose - Positive urine glucose - ↑ Glycohemoglobin - Ketones in blood and urine - ↑ Anion gap - ↓ Bicarbonate - ↓ Blood pH - ↑ BUN - ↑ Osmolality - ↑ Cholesterol - ↑ Triglycerides ## **Hormones** | HORMONE | SOURCE | EFFECT | ACTION | | ---------------- | ---------------------- | ------ | ------------------------------------------------------------------------------------------- | | INSULIN | β cells of pancreas | ↓ | stimulates glucose uptake by cells | | GLUCAGON | α cells of pancreas | ↑ | glycogenolysis | | ACTH | Anterior pituitary | ↑ | insulin antagonist, glycogenolysis & gluconeogenesis | | GROWTH HORMONE | Anterior pituitary | ↑ | insulin antagonist, gluconeogenesis & lipolysis | | CORTISOL | adrenal cortex | ↑ | insulin antagonist, gluconeogenesis & lipolysis | | HPL | Placenta | ↑ | insulin antagonist | | EPINEPHRINE | adrenal medulla | ↑ | inhibits insulin secretion, glycogenolysis & lipolysis | | T3 & T4 | Thyroid gland | ↑ | glycogenolysis, gluconeogenesis & intestinal absorption of glucose | | SOMATOSTATIN | δ cells of pancreas | ↑ | inhibits insulin, glucagon & GH | ## **Diabetes Diagnosis** | | | | ---------------------------- | ------------------------------- | | FASTING PLASMA GLUCOSE | >126mg/dL | | 2-HR OGTT | > 200mg/dL during OGTT | | RANDOM PLASMA GLUCOSE | > 200mg/dL + symptoms | | HBA1C | ≥ 6.5% | | NORMAL FASTING GLUCOSE | 70 to 99 mg/dL (3.9 to 5.5mmol/L) | | IMPAIRED FASTING GLUCOSE | 100 to 125 mg/dL (5.6 to 6.9 mmol/L) | | PROVISIONAL DIABETES DIAGNOSIS | ≥ 126mg/dL (7.0mmol/L) | | | | | ---------------------------- | ------------------------------- | | NORMAL GLUCOSE TOLERANCE | ≤ 140 mg/dL (≤ 7.8 mmol/L) | | IMPAIRED GLUCOSE TOLERANCE | > 140 to 199mg/dL (7.8 to 11.1 mmol/L) | | PROVISIONAL DIABETES DIAGNOSIS | ≥ 200mg/dl (≥ 11.1 mmol/L) | ## **Diabetes Diagnosis Methods** | **ONE-STEP APPROACH** | **TWO-STEP APPROACH** | | -------------------------------------------------------------------------------------------- | ---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | • 2-hr OGTT using 75g Glucose load performed at least 8hrs of Fasting | • Initial measurement of plasma glucose at 1-hr post load (50g); if ≥140mg/dL, do 3-hr OGTT using 100g glucose performed after 8-14 hrs of Fasting w/ at least 3 days unrestricted diet (>150g CHO/day) | | Fasting = ≥ 92 mg/dL | Fasting = ≥ 95mg/dL | | 1-hr PG = > 180mg/dL | 1-hr PG = > 180 mg/dL | | 2-hr PG = > 153 mg/dL | 2-hr PG = > 155 mg/dl | | | 3-hr PG = > 140 mg/dL | ## **Glycogen Storage Diseases (GSD)** | I - von Gierke * Most common | ENΞΥΜΕ DEFICIENT | | ---------------------------- | --------------------------------------------------------------------------------------------------------------------------------------------------- | | II - Pompe | α-1,4-glucosidase | | III - Cori Forbes | De brancher enzyme | | IV - Andersen | Brancher enzyme | | V - McArdle | Muscle Phosphorylase | | VI - Hers | Liver Phosphorylase | | VII - Tarui | Muscle phosphopructokinase | | XI - Fanconi-Bickel | Glycogen transporter 2 | | 0 | Glycogen synthetase | ## **Glucose Specimen Requirements** - Standard specimen: FASTING VENOUS PLASMA [N.V. 70 to 110mg/dL] - Whole blood glucose is ~ 10 to 15% (10 to 12%.) LOWER compared to serum/plasma - Capillary > Venous < Arterial - Conventional (mg/dL) → 91 unit (mmol/L): 0.0555 - Fasting Hours: 8 to 10 hours (not longer than 16hrs) - Geparation of cells from serum: 30 to 60mins - Glycolysia lowers glucose by 5 to 7% (5 to 10 mg/dL) per hour. - Standard Anticoagulant: 2mg NaF/ML OF WB (w/ K' oxalate), if alone 6 to 10mg/ml (prevents glycolysis up to 48 to 72 hours (2-3 days)) - Glucose Metabolism: 7mg/dL/hr (room temp); 2mg/dL/hr (ref temp) - Renal threshold: 160 to 180mg/dL or 8.8 to 9.9 mmol/L - CTF glucose concentration: ~ 60 to 70% that of plasma; collect blood 1 to 2hrs prior ## **Glucose Measurement Methods** | DIRECT / CHEMICAL | INDIRECT/ENZYMATIC | | ----------------------------------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | | • CUPRIC ION REDUCTION | • CLUCOGE OXIDASE - most specific for B-D-glucose | | > FOLIN WU → phosphomolybdenum blue | > COLORIMETRIC/SAIFER GERNSTENFIELD | | > NELSON SOMOGYI → arsenomolybdenum blue | Glucose + D₂ + H₂O glucose oxidase → gluconic acid + H202 | | > NEOCUPROINE → cuprous-neocuproine complex | H₂O₂ + chromogen peroxidase, oxidized chromogen + O2 | | • FERRIC REDUCTION | > POLAROGRAPHIC | | > HAGEDORN JENSEN - Inverse Colorimetry | H₂O2 removed by: Catalase & Molybdate | | Reagent: Potassium Ferricyanide | • HEXOKINAGE - reference method | | Product: Disappearance of color @ 400nm | * G6PD is highly specific | | • CONDENSATION: ORTHOTOLUIDINE/DUBOWSKI | * NADPH formation @ 340nm | | Reagent: o-toluidine, glacial acetic acid, 100°( heat | • GLUCOSE DEHYDROGENASE | | End color: green or bluish green | * MUTAROTASE - a-D-glucose → B-D-glucose | ## **Lipids** | LIPOPROTEIN | OTHER NAME | APOLIPOPROTEIN | SIGNIFICANCE | | ------------ | --------------------- | ---------------- | 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| | HDL | Alpha lipoprotein | Apo A-1, ApoE | Inversely related to CHD; GOOD cholesterol | | VLOL | Pre-beta lipoprotein | ApoB-100, ApoE | Transports ENDOGENOUS TAG from the liver | | LDL | Beta lipoprotein | Apo B-100 | Primary marker for CHD & atherosclerosis; BAD cholesterol | | LDL | Beta lipoprotein | Apo B-100 | Primary marker for CHD & atherosclerosis; BAD cholesterol