Clinical Chemistry Path Seminar Exam #2

Clinical Chemistry

• Study of chemical processes and substances in body fluids (mainly blood and urine)

• Measures analytes to assess organ function and disease

Why Clinical Chemistry Matters for PathA’s:

• Correlate lab data with gross/microscopic findings

• Understand cause of death or surgical indications

• Communicate effectively with clinicians and pathologists

• Example: Elevated liver enzymes + fatty liver on gross exam

most common chemistry panels

• basic metabolic panel (BMP)

• comprehensive metabolic panel (CMP)

• lipid panel

• Other frequent panels: Cardiac markers, thyroid, liver panel, HbA1c

Basic Metabolic Panel (BMP) analytes

Glucose, electrolytes, BUN, creatinine

Comprehensive Metabolic Panel (CMP) anylytes

BMP + liver enzymes, albumin, total protein

lipid panel anylytes

Cholesterol, triglycerides, HDL, LDL

Hyperglycemia/Diabetes:

• Originally two forms: Type I (insulin-dependent or IDDM) &  Type II (non-insulin dependent or NIDDM)

• No more juvenile-onset and adult-onset

• No more IDDM or NIDDM

• Just type I and II

Diabetes Mellitus

• Metabolic disorders of carbohydrate metabolism

• Glucose is underutilized

• Individuals can experience ketoacidosis, coma

• As disease progresses, patients are at risk for other complications

Diabetes Mellitus Type 1

• 5-10% of people with DM

• Polyuria, polydipsia, rapid weight loss

• Insulin deficient from loss of pancreatic islet β-cells

• Some have antibodies (autoimmune) and some do not (idiopathic)

Diabetes Mellitus Type II

• 90% of cases

• Minimal symptoms

• Not prone to ketosis

• Not dependent on insulin (insulin levels could be normal, increased, or decreased)

• Mostly impaired insulin action

• Obesity – weight loss improves hyperglycemia

• Some require medication or insulin therapy

Gestational Diabetes Mellitus (GDM): 

• First recognized during pregnancy

• Increased risk of subsequent diabetes, mostly type II

• ↑ glucose crosses placenta, ↑ baby glucose

• Baby’s pancreas ↑ insulin, extra stored as fat

• Average risk mother is tested 24-28wk gestation

Clinical Complications of Diabetes Mellitus:

• Kidney failure

• Neuropathies

• Vascular disease problems (amputations) 

• Retinopathies - blindness

Normal Fasting Blood Sugar (FBS):

Normal: ≤ 110 mg/dL

Increased Fasting Blood Sugar Eval

• DM

• Cushing’s disease

• Pheochromocytoma, gigantism, acromegaly

• Pituitary adenoma

Decreased Fasting Blood Sugar Eval

• Insulinomas 

• Addison’s disease

• Malabsorption

• Insulin overdose (accidental or deliberate)

Glucose Tolerance Test (GTT) Performed for

• Family hx of diabetes

• Obesity

• Unexplained episodes of hypoglycemia

• Women who have hx of large infant delivery, stillbirths, neonatal death, spontaneous abortions

GTT Procedure:

• Patient consumes diet with > 150g of carbs 3 days before test

• Patient fasts for 12-16 hours before test

• Draw fasting blood sugar

• Patient drinks specially formulated glucose solution

• Blood samples are obtained at 30 minutes, 1hr, 2hr, 3hr after

Hemoglobin A1c

• Blood glucose bound to RBC

• Rate of formation of GHb is directly proportional to concentration of glucose in blood

• Provides indication of avg blood sugar over preceding 6-8 weeks

• Free of day-to-day fluctuations

• Depends on RBCs having normal lifespan of 120 days

Lipids

• Hydrophobic

• Serve as hormones

• Energy source

• Aids in digestion

• Structural component in cell membranes

• Involved in atherosclerosis

• Exogenous – caloric intake

• Endogenous – liver synthesizes lipids

Cholesterol

• Mostly from consumption of animal products but also from biliary secretions

• Made soluble through emulsification

• Absorbed in middle jejunum to terminal ileum (fiber would carry it out)

• Once inside the intestinal mucosal cell it is packaged with trigs and phospholipids into large lipoprotein particles called chylomicrons

• Chylomicrons are secreted into lymph and enter the circulation delivering the dietary lipid to liver and peripheral tissues

Triglycerides

• Constitute 95% of tissue storage fat

• Dietary triglycerides are digested in the duodenum and absorbed in the proximal ileum

• Trigs are delivered to the liver and peripheral cells after they are hydrolyzed to fatty acids by lipases from pancreas

Lipoproteins

• Chylomicrons

• VLDL – very low-density lipoproteins

• LDL – low-density lipoproteins

• HDL – high-density lipoproteins

Chylomicrons

• Largest of the fractions, lowest density

• High trig, low protein

• Primary carrier of exogenous lipids

• Creamy top forms on serum because of density differences

• Released into lymphatics

VLDL

• Primarily composed of trigs

• Synthesized in liver

LDL

• Traditionally considered “bad cholesterol”

• Makes up the majority of cholesterol

• Carrier of endogenous cholesterol from liver to tissues

• Is taken up by cells and once inside, cholesterol is separated and used for cell membranes

• Important for brain function

HDL

• “good cholesterol”

• Contains a lot of protein and a little chol and trig

• Secreted into blood

• Can bind with LDL and remove it from blood

• Clears excess cholesterol from blood

• Synthesized in liver and intestines

CK/CPK and Isoenzymes:

• Creatinine kinase or creatinine phosphokinase

• CK-MB is cardiac-specific

• Helps tell if elevated CK is from heart (MB) or skeletal muscle (MM)

Troponin

• Unique to heart muscle and highly concentrated in cardiomyocytes

• Released with very small areas of myocardial damage in 3-12 hrs, peak 24-48hrs.

• Levels return to normal in 5-14 days

• Single sample can be misleading so serial sampling recommended: 0,4,8, and 12 hrs. after chest pains

Tropinin I and Tropinin T

• Troponin I is cardiac specific

• Increases in small infarcts, myocardial injury during surgery

• Troponin T is more sensitive, less specific

• Increases in acute MI, unstable angina, myocarditis

LDH

• Not cardio specific

• Widely distributed intracellular enzyme

                    -Kidney, heart, skeletal muscle, brain, liver, lungs

• When increased indicates cellular death and leakage of enzyme from cell

AST (aspartate transaminase):

• Present in tissues with high metabolic activity

                       -Heart, liver, skeletal muscle, kidney, brain, pancreas, spleen, lungs

• Released into circulation following injury or cell death

• Usually ordered with ALT

BNP (brain natriuretic peptide):

• Originally isolated from porcine brain tissue

• Released from cardiac ventricles

• Sensitive marker for changes in ventricular physiology

Myoglobin

• Present in cardiac and skeletal muscle

• Not specific to myocardial muscle

• Excreted in urine

• Increase 1-4hrs, peak at 6-7hrs, normal within 24hrs

Hyperlipidemia

• may be primary or secondary: 

• Diet, exercise, obesity

• Genetics: enzyme, structural proteins, receptors involved in metabolism

Secondary causes of hyperlipidemia

• Exogenous - certain drugs

• Endocrine and metabolic

• Storage disease – Gaucher, Niemann-Pick, etc.

• Renal

• Hepatic

• Acute and transient – burns, trauma(surgery)

• Anorexia, starvation, SLE

4 main kinds of lipoproteins

chylomicrons, VLDL, LDL, HDL