Lesson 1 of 630 min read

Clinical Chemistry

Carbohydrates, Lipids, Proteins, Enzymes, and Organ Function Tests

In This Lesson

1. Carbohydrate Metabolism 2. Lipid Profile 3. Proteins & Amino Acids 4. Enzymes 5. Liver Function Tests 6. Kidney Function Tests 7. Electrolytes & ABG 8. Cardiac Markers

1. Carbohydrate Metabolism

Glucose Testing

Diagnostic Criteria

Test	Normal	Prediabetes	Diabetes
FBS	<100 mg/dL	100-125	≥126
OGTT (2hr)	<140 mg/dL	140-199	≥200
HbA1c	<5.7%	5.7-6.4%	≥6.5%
Random	-	-	≥200 + symptoms

Glucose Methods

Enzymatic Methods

Glucose Oxidase: Specific for glucose; GOD-POD reaction
Hexokinase: Reference method; NADPH measured at 340nm
Glucose Dehydrogenase: Uses NAD/NADP

Interferences

• Ascorbic acid: False decrease (GOD-POD)
• Hemolysis: Glycolytic enzymes
• Lipemia: Turbidity interference

Hemoglobin A1c

Definition: Glycated hemoglobin; glucose attached to N-terminal valine of beta chain
Reflects: 2-3 month average blood glucose (RBC lifespan)
Methods: Ion-exchange chromatography, HPLC, immunoassay
Interferences: Hemoglobinopathies (HbS, HbC), hemolysis, uremia
Target: <7% for most diabetics

Hypoglycemia & Hyperglycemia

Hypoglycemia (<70 mg/dL)

• Insulin overdose
• Insulinoma
• Liver failure
• Alcohol ingestion
• Addison's disease

Hyperglycemia

• Diabetes mellitus (Type 1, 2)
• Pancreatitis
• Cushing syndrome
• Stress/trauma
• Medications (steroids)

2. Lipid Profile

Lipoproteins

Classes (by density)

Chylomicrons: Largest; dietary TG transport
VLDL: Endogenous TG; liver origin
LDL: "Bad" cholesterol; atherogenic
HDL: "Good" cholesterol; reverse transport

Apolipoproteins

Apo A-I: Major HDL protein; LCAT activator
Apo B-100: LDL; LDL receptor ligand
Apo B-48: Chylomicrons
Apo E: Remnant clearance

Reference Ranges

Desirable Levels

Total Cholesterol: <200 mg/dL
LDL-C: <100 mg/dL (optimal)
HDL-C: >40 M, >50 F mg/dL
Triglycerides: <150 mg/dL

Risk Factors

High LDL → Atherosclerosis
Low HDL → CVD risk
High TG (>500) → Pancreatitis
TC/HDL ratio >4.5 → Risk

Friedewald Equation

LDL = TC - HDL - (TG/5)

Limitations: Invalid if TG >400 mg/dL or Type III hyperlipidemia
Specimen: Fasting (10-12 hours) required for TG
Direct LDL: Homogeneous assays available (no fasting needed)

3. Proteins & Amino Acids

Total Protein & Albumin

Total Protein: 6.0-8.0 g/dL; Biuret method (purple color)
Albumin: 3.5-5.0 g/dL; BCG/BCP methods; made in liver
Globulins: TP - Albumin; includes immunoglobulins
A/G Ratio: 1.2-2.0; decreased in liver disease, inflammation

Serum Protein Electrophoresis

Fractions (Anode to Cathode)

Albumin: 60%; transports bilirubin, hormones, drugs
Alpha-1: AAT, AFP
Alpha-2: Haptoglobin, Ceruloplasmin
Beta: Transferrin, C3, LDL
Gamma: Immunoglobulins (IgG, IgA, IgM, IgD, IgE)

Pattern Recognition:

• M-spike (monoclonal): Multiple myeloma
• Polyclonal: Chronic inflammation
• Beta-gamma bridging: Cirrhosis

4. Enzymes

Enzyme Kinetics

Michaelis-Menten: V = Vmax[S]/(Km + [S])
Km: Substrate concentration at 1/2 Vmax; measure of affinity
Zero-order: Substrate excess; rate = constant
First-order: Rate proportional to substrate concentration

Clinically Important Enzymes

Enzyme	Source	Clinical Use
ALP	Liver, Bone, Intestine	Biliary obstruction, bone disease
AST	Heart, Liver, Muscle	Hepatitis, MI (less specific)
ALT	Liver (specific)	Hepatitis (most specific liver)
GGT	Liver, Kidney	Alcohol, biliary disease
LDH	All tissues	Non-specific tissue damage
CK	Muscle, Heart, Brain	Muscle damage, MI
Amylase/Lipase	Pancreas, Salivary	Pancreatitis

5. Liver Function Tests

Bilirubin Metabolism

RBC breakdown → Unconjugated (indirect) bilirubin
Transported to liver bound to albumin
Conjugated with glucuronic acid (direct bilirubin)
Excreted in bile → Urobilinogen → Stercobilin (feces)

Prehepatic

↑ Indirect; Hemolysis

Hepatic

↑ Both; Hepatitis

Posthepatic

↑ Direct; Obstruction

Liver Enzymes Pattern

Hepatocellular (ALT > ALP)

• Viral hepatitis
• Drug-induced liver injury
• Ischemic hepatitis
• AST:ALT >2 suggests alcohol

Cholestatic (ALP > ALT)

• Biliary obstruction
• Primary biliary cholangitis
• Drug-induced cholestasis
• GGT confirms hepatic ALP

6. Kidney Function Tests

Markers of Kidney Function

Test	Reference Range	Notes
BUN	7-20 mg/dL	Urea nitrogen; diet, protein intake affect
Creatinine	0.7-1.3 (M), 0.6-1.1 (F)	Muscle mass related; best endogenous marker
eGFR	>90 mL/min/1.73m²	CKD-EPI equation; <60 = CKD
Cystatin C	0.6-1.0 mg/L	Not affected by muscle mass

BUN/Creatinine Ratio

Normal: 10-20:1
>20:1 (Prerenal): Dehydration, CHF, GI bleed, high protein
<10:1 (Intrarenal): Acute tubular necrosis, malnutrition, liver disease
Normal ratio, both elevated: Postrenal obstruction or intrinsic renal disease

7. Electrolytes & ABG

Major Electrolytes

Sodium: 136-145 mEq/L; major extracellular cation
Potassium: 3.5-5.0 mEq/L; major intracellular cation
Chloride: 98-106 mEq/L; follows sodium

Bicarbonate: 22-28 mEq/L; buffer system
Calcium: 8.5-10.5 mg/dL total; 4.5-5.5 ionized
Magnesium: 1.8-2.4 mg/dL

Anion Gap

AG = Na - (Cl + HCO3)

Normal: 8-12 mEq/L
High AG acidosis (MUDPILES): Methanol, Uremia, DKA, Propylene glycol, INH/Iron, Lactic acidosis, Ethylene glycol, Salicylates

Arterial Blood Gas

pH: 7.35-7.45
pCO2: 35-45 mmHg (respiratory component)
HCO3: 22-28 mEq/L (metabolic component)
pO2: 80-100 mmHg

8. Cardiac Markers

Markers for Myocardial Infarction

Marker	Rises	Peaks	Normal
Troponin I/T	3-6 hr	12-24 hr	7-14 days
CK-MB	3-8 hr	12-24 hr	2-3 days
Myoglobin	1-4 hr	6-9 hr	24 hr

Key Points:

• Troponin: Most specific and sensitive for cardiac damage
• High-sensitivity troponin (hs-cTn): Earlier detection
• BNP/NT-proBNP: Heart failure marker, not MI

Key Takeaways

✓HbA1c ≥6.5% or FBS ≥126 mg/dL = Diabetes diagnosis
✓LDL = TC - HDL - (TG/5) - only valid if TG <400
✓ALT is most liver-specific; AST:ALT >2 suggests alcohol
✓BUN/Cr >20:1 = prerenal azotemia; <10:1 = intrarenal
✓Troponin is the gold standard for MI diagnosis

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