Carbohydrates, Lipids, Proteins, And Nitrogen Compounds

Carbohydrate metabolism and diabetes diagnosis

Glucose is the analyte you will see most on the MLS chemistry section. Memorize the American Diabetes Association diagnostic thresholds, because items often give a value and ask for the interpretation. Diabetes mellitus is diagnosed by any of: fasting plasma glucose (FPG) >=126 mg/dL, a 2-hour oral glucose tolerance test (OGTT) value >=200 mg/dL, HbA1c >=6.5%, or a random glucose >=200 mg/dL with classic symptoms. Impaired (prediabetes) ranges are FPG 100-125 mg/dL or HbA1c 5.7-6.4%.

Know the methods. The reference (most specific) glucose method is the hexokinase reaction, which couples to glucose-6-phosphate dehydrogenase (G6PD) and reads NADPH at 340 nm. Glucose oxidase is also common but is subject to negative interference from ascorbate and uric acid. CSF glucose runs roughly 60-70% of plasma; a low CSF:plasma ratio with high protein suggests bacterial meningitis.

Lipids and the Friedewald calculation

Lipids are a guaranteed calculation target. Friedewald: LDL = Total cholesterol - HDL - (triglycerides / 5). The triglyceride/5 term estimates VLDL cholesterol. The formula is invalid when triglycerides exceed 400 mg/dL (you must run a direct LDL instead) and is unreliable in type III dysbetalipoproteinemia. Worked example: TC 240, HDL 40, TG 150 -> LDL = 240 - 40 - 30 = 170 mg/dL (high). A common trap is forgetting the patient must be fasting 9-12 hours for valid triglycerides.

• Desirable total cholesterol < 200 mg/dL
• HDL < 40 mg/dL (men) is a cardiac risk factor; >=60 is protective
• Chylomicrons float as a creamy layer on standing serum; VLDL turbidity stays dispersed

Proteins and nitrogen compounds

Total protein = albumin + globulins. Serum protein electrophoresis (SPEP) separates five bands: albumin, alpha-1, alpha-2, beta, gamma. A sharp narrow spike in the gamma region (an M-protein) suggests multiple myeloma or other monoclonal gammopathy; a polyclonal broad gamma rise reflects chronic inflammation. A decreased albumin with a beta-gamma bridge points to cirrhosis. Albumin maintains 80% of plasma oncotic pressure; the bromocresol green (BCG) dye-binding method is standard.

Nitrogen compounds are end products of protein catabolism. Urea (measured as BUN, blood urea nitrogen) and creatinine assess renal function. Because BUN reports only the nitrogen portion, convert urea to BUN by multiplying by 0.467 (or BUN x 2.14 = urea). A BUN:creatinine ratio > 20:1 indicates prerenal azotemia (dehydration, GI bleed); a ratio < 10:1 suggests intrinsic liver/renal causes. Creatinine is produced at a constant rate from muscle and is the better GFR marker; the Jaffe (alkaline picrate) method is classic but suffers positive interference from ketones and cephalosporins.

Uric acid rises in gout, renal failure, and tumor lysis.

Worked correlations and traps

Expect items that hand you a panel and ask for the disease. A glucose of 350 mg/dL with ketones, a high anion gap, and a fruity-breath history points to diabetic ketoacidosis; a glucose of 45 mg/dL after delayed serum separation is almost always in vitro glycolysis, not true hypoglycemia, because red cells consume glucose at roughly 5-7% per hour at room temperature. Always draw glucose into a gray-top (sodium fluoride) tube when a delay is expected, since fluoride inhibits glycolysis.

For proteins, a low albumin with a low total protein and edema suggests nephrotic syndrome or malnutrition, whereas a low albumin with a high globulin (a reversed A:G ratio) suggests chronic infection, cirrhosis, or myeloma. A Bence Jones protein (free monoclonal light chains) found in urine but missed on a routine dipstick (which detects mostly albumin) is a classic myeloma trap. Microalbuminuria (30-300 mg/day) is the earliest lab sign of diabetic nephropathy and is reported as an albumin-to-creatinine ratio.

For lipids, remember the standing-serum test: a creamy layer over clear serum indicates chylomicrons, while uniform turbidity indicates elevated VLDL (triglycerides). Apolipoprotein B reflects atherogenic particle number, and lipoprotein(a) is an independent inherited cardiac risk factor. When triglycerides exceed 400 mg/dL, refuse the Friedewald estimate and report a direct LDL instead -- choosing the calculated value anyway is the most common distractor on these items.

Glucose tolerance, HbA1c chemistry, and ketones

The oral glucose tolerance test (OGTT) uses a 75 g glucose load for nonpregnant adults and the 2-hour value of 200 mg/dL or higher confirms diabetes. Gestational diabetes screening commonly uses a 50 g 1-hour challenge followed by a confirmatory 100 g 3-hour test with stricter cutoffs. HbA1c measures glucose irreversibly bound to the N-terminal valine of the hemoglobin beta chain, so it reflects the preceding 8-12 weeks of glycemia; conditions that shorten red cell survival (hemolysis, recent transfusion, sickle trait, pregnancy) falsely lower it, while iron deficiency can falsely raise it.

Boronate affinity and HPLC are the reference HbA1c methods, and HPLC also separates hemoglobin variants. Ketones (acetoacetate, beta-hydroxybutyrate, acetone) rise in uncontrolled type 1 diabetes; nitroprusside dipstick reagents detect acetoacetate but miss beta-hydroxybutyrate, the dominant ketone in severe ketoacidosis, so a serum beta-hydroxybutyrate measurement is preferred when DKA is suspected -- a frequently tested method limitation.