Clinical Lab Medicine IV

What is clinical chemistry?

Study of chemical components in body fluids (blood, urine) to assess organ function and disease

Measures analytes to assess organ functions and disease

Why is it important for PathA?

Correlate lab data with gross/microscopic findings

Helps determine cause of disease/death

Communicate effectively with clinicians and pathologists

What are some analytes clinical chemistry assess?

Electrolytes

Enzymes

Hormones

Metabolites

What does the basic metabolic panel (BMP) test for?

Glucose

Electrolytes

BUN

Creatinine

What does the comprehensive metabolic panel (CMP) test for?

BMP + liver enzymes, albumin, total protein

What does the lipid panel test for?

Cholesterol

Triglycerides

HDL

LDL

What do other frequent panels test for?

Cardiac markers

Thyroid

Liver panel

HbA1c

Hyperglycemia/Diabetes overview

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

What is the difference between diabetes and diabetes mellitus?

Diabetes — A general term for conditions characterized by excessive urination (polyuria)

Diabetes mellitus — The specific, common metabolic disorder causing high blood sugar

Diabetes mellitus overview

Metabolic disorders of carbohydrate metabolism

Glucose is underutilized

Individuals can experience ketoacidosis, coma

As disease progresses, patients are at risk for other complications

What is diabetes mellitus?

Disorder of carbohydrate metabolism → Hyperglycemia

What is the type I DM mechanism?

Autoimmune destruction of beta-cells → No insulin

What is the type II DM mechansim?

Insulin resistance

Which type of DM is most common?

Type II (~90%)

What is a classic type I symptom?

Polyuria

Polydipsia

Weight loss

What is a classic type II symptom?

Obesity — Weight loss improves hyperglycemia

Which type causes ketoacidosis?

Type I

DM type I overview

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)

DM type II overview

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

What are long-term complications of DM?

Nephropathy

Neuropathy

Retinopathy

Vascular disease

Gestational diabetes mellitus overview

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

Fasting blood sugar (FBS) overvoew

No caloric intake for at least 8hrs

• Normal: ≤ 110 mg/dL

• Pre-diabetes (monitor): 110-125 mg/dL

• Diabetes: ≥ 126 mg/dL

What are normal FBS levels?

≤ 110 mg/dL

What can increase FBS?

DM

Cushing’s disease

Pheochromocytoma, gigantism, acromegaly

Pituitary adenoma

What can decrease FBS?

Insulinomas

Addison’s disease

Malabsorption

Insulin overdose

When is a glucose tolerance test (GTT) performed?

Family hx of diabetes

Obesity

Unexplained episodes of hypoglycemia

Women who have hx of large infant delivery, stillbirths, neonatal death, spontaneous abortions (pregnancy complications)

What is the procedure for a GTT?

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

What does HbA1c measure?

Average glucose over 6-8 weeks

Hemoglobin A1c overview

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

What is the function of chylomicrons?

Carry dietary lipids

What are some roles of 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

What is VLDL function?

Carry triglycerides from liver

Primarly composed of trigs

What is LDL (“bad”) function?

Delivers cholesterol from liver to tissue → Atherosclerosis

Makes up the majority of cholesterol

Important for brain function

What is HDL (“good”) function?

Removes cholesterol from blood

Contains lots of protein, a little cholesterol and trig

Can bind to LDL to remove it

Cholesterol overview

Take from:

• Consumption of animal products

• Biliary secretions

Made soluble through emulsification

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

Cholesterol packaged with trigs and phospholipids into large lipoprotein particles (chylomicrons)

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

Triglycerides overview

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

What are some of the different lipoproteins?

Chylomicrons

VLDL – very low-density lipoproteins

LDL – low-density lipoproteins

HDL – high-density lipoproteins

What is the purpose of CK/CPK and isoenzymes?

Creatinine kinase or creatinine phosphokinase

CK-MB is cardiac-specific

Helps tell if elevated CK is from heart (MB) vs skeletal muscle (MM) injury

What is the purpose of 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

Differentiate between troponin I and troponin 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

What are normal lipid values?

Total cholesterol: < 200 mg/dL

LDL: < 130 mg/dL

HDL: ≥50 mg/dL

Trig: <150 mg/dL

What causes hyperlipidemia?

Diet

Obesity

Genetics

Disease

(Hyperlipidemia → Atherosclerosis → MI)

What is the purpose of 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

What is the purpose of 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

Why are LDH and AST least useful?

NOT cardiac-specific

What is the purpose of BNP (drain natriuretic peptide)?

Originally isolated from porcine brain tissue

Released from cardiac ventricles

Sensitive marker for changes in ventricular physiology

Heart failure (ventricular stress)

What is the purpose of 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

What is the earliest marker used in lab testing?

Myoglobin (1-4 hrs)

• But NOT specific

What is the function of albumin?

Maintains osmotic pressure and transport

What will low albumin cause?

Edema

What does hypoalbuminemia cause?

Liver disease

Nephrotic syndrome

Malnutrition

What does hyperalbuminemia cause?

Dehydration

Not really any clinical significance

How will increased indirect bilirubin affect liver function testing?

Hemolytic anemia

Trauma

How will increased direct bilirubin affect liver function testing?

Cancer in the head of pancreas

Choledocholithiasis

Obstructive jaundice

What is the difference between ALT and AST?

ALT = More liver-specific

AST = less specific

When will ALP levels increase?

Biliary (liver) obstruction

Increases in proportion to new bone formation

What will any levels of ammonia affect?

Affect acid/base balance

Brain function

What is the purpose of ALT (alanine aminotransferase)?

Can disease liver disease

Compare and contrast amylase and lipase

Both increase in pancreatitis

Lipase = More specific and lasts longer

• Provides better sensitivity and specificity for pancreatic damage

What does amylase do?

Changes starch into sugar

Produced in saliva and pancreas

What does lipase do?

Hydrolyzes dietary trigs

What does BUN (blood urea nitrogen) measure?

Protein metabolism waste

When does BUN increase?

Kidney dysfunction

Dehydration

Why is creatinine better than BUN?

More specific for kidney function

What is the best indictor for kidney function than BUN?

Creatinine clearance

What does the creatine clearance testing test?

Measures urine creatinine output over 24hr period

What is the purpose of electrolytes?

Maintenance of osmotic pressure in fluid spaces

Propagation of nerve impulses

Muscle contraction

Acid-base balance

What will hyponatremia (low Na) cause?

Excess water

• Severe burn, diarrhea

• CHF, Addison’s disease

• Diuretics

What will hypernatremia cause?

Dehydration

Crushing disease

Diabetes insipidus

What will hypokalemia (low K) cause?

Vomiting, diarrhea, sweating

Starvation, malabsorption

Diuretics

What will hyperkalemia cause?

Renal failure

DIC, burns, surgery, chemo

Addison’s disease

Hemolyzed specimen

What is the most common cause of hypercalcemia (high Ca)?

Hyperparathyroidism → PTH producing adenoma

What is the main role of chloride?

Acid-base balance

What is the most abundant cation?

Na+

Why is K+ important for the cell?

Principle electrolyte of intracellular fluid

Primary buffer within the cell

Where can you mind the most Ca2+ in the body?

Stored in bones and teeth

What can measuring Ca2+ levels show?

Parathyroid function

Calcium metabolism

Malignancy activity

What will hypochloremia (low Cl-) cause?

Severe vomiting, water intoxication

Addison’s disease

What will hyperchloremia (high Cl-) cause?

Cushing’s disease

Dehydration