Enzymes Flashcards
Enzyme: Definition
• Substance that increases the rate of a reaction without itself being consumed or altered
Increased levels of enzymes in the plasma are due to:
- Cell leakage: Wear and tear & Disease
- Increased synthesis: Drug & Disease
- Multiplication of cells which produce the enzyme
• Active growth (Ie. Pregnancy/childhood)
• Tissue repair (Ie. Fracture)
• Malignancies (Ie. Cancer Cells) - Duct obstruction
• Levels of enzyme activity reached in plasma directly related to:
Amount of tissue damaged
ACP: Greatest Concentration
• Liver, spleen, RBCs, platelets, bone marrow
• Prostate gland (Ie. Older Patient)*
ACP is used to diagnose and stage
Prostatic carcinoma
ACP: Test Interferences
• Avoid hemolysis (destruction of RBCs)
• Falsely high levels may occur after prostate stimulation
ACP: Increased Levels (4)
• Prostatic carcinoma
• Multiple myeloma
• Hyperparathyroidism
• Cancer metastasis to bone
ACP: Clinical Significance
• Measurement for diagnosis and management of prostate cancer has largely been replaced by prostate specific antigen (More important test)
• Elevations of ACP found in prostatic cancer with metastases (80%)
• When carcinoma remains localized to prostate gland, normal or slight elevations seen.
Alkaline Phosphatase (ALP) is an enzyme present in:
Practically all tissues of the body
ALP: Highest Concentrations
-Bone & Liver*
-Others: Billiary tract epithelium, intestinal mucosa, placenta
Regan Isoenzyme is present in about:
5-15% of patients (Cancer)
ALP: Interfering factor
Recent ingestion of food
ALP: Clinical Significance
-Kids (2-3x more than adults)
-Hepatobiliary disease: More elevated in extrahepatic
-Bone Disease: Increased osteoblastic activity
-3rd Trimester of Pregnancy
ALP: Bone Diseases
-Highest Levels: Paget’s
-Very High Levels: Bone Cancer
-Moderate Rises: Osteomalacia
Creatine Phosphatase (CPK) is typically measured due to:
Myocardial injury (CPK-2 Heart) or Infarct
• CPK-BB (1)
• CPK-MM – normally comprises almost all circulatory CPK enzymes-90% (3)
During myocardial injury/infarct, CPK levels: (Rise, Peak, Normal)
Rise 3-6 hours after infarct, peaks at 12-24 hours, normal 12-48 hours after Injury-Quick
CPK-3 Test Interferences (Elevated)
• IM injections (CPK 3)
• Strenuous exercise (CPK 3)
CPK Test Interferences: Decreased
Early Pregnancy
CPK: Clinical Significance
• Muscular dystrophy: CPK 3 (MM) 50x Normal
(May be elevated before clinically apparent)
• Myocardial infarction: Sensitive & Specific CPK-2 (MB)
CPK-1: Clinical Significance (Miscellaneous)
• Acute cerebrovascular disease & cerebral ischemia: CPK-1 (BB)
• Epilepsy: CPK-1 (BB)
Gamma glutamyltransferase (GGT) is used to detect:
Liver cell dysfunction
GGT very accurately reveals:
Cholestasis
GGT elevations usually parallel:
ALP (GGT is more sensitive)
GGT can detect:
Alcohol ingestion (rapidly rises)
• Elevated 4-10 days after acute myocardial infarction – not clear why (2-6 weeks)
GGT
GGT: Clinical Significance
• MCC of elevation – active liver disease
• Only moderate elevations in hepatitis
• High elevations – primary or metastatic neoplasms (Liver)
• Small increases – fatty liver, drug intoxication
• Infectious mono and cytomegalovirus (hepatomegaly)
GGT is highest in: Which conditions?
Intra or post-hepatic biliary obstruction (Cholelithiasis)
• Chronic alcohol use (MCV-1st)
Hydrolase (Amylase): Greatest Concentration (Location)
Pancreas and Salivary Glands
Hydrolase (Amylase): Test interference
Ingestion of alcoholl
Hydrolase (Amylase) is the most common lab test in diagnosis of:
Acute pancreatitis
Hydrolase (Lipase): MCC of elevation
Acute pancreatitis (Lipase produced only in the pancreas)
Hydrolase (Lipase): Patient Prep
8-12 hour fast
Hydrolase (Lipase): Clinical Significance
• Acute pancreatitis – more specific than amylase
• Levels rise slightly later than amylase, remain high longer (7-10 days)
Lactate Dehydrogenase (LDH): Highest Levels (5)
• Liver: acute liver disease
• Heart: myocardial infarction
• Lung
• Skeletal muscle
• RBCs: megaloblastic anemia, hemolytic anemias
LDH: Clinical Significance
- Myocardial infarction
- Liver disease
- Megaloblastic and hemolytic anemia
- Progressive Muscular Dystrophy
LDH: Myocardial Infarction
• Diagnostic value – when CPK-MB elevation has passed, LDH remains elevated (7-12 days)
• Elevations up to 10X higher
LDH: Megaloblastic and Hemolytic Anemia
(Which anemias have elevations?)
• Not specific enough to be diagnostic
• Marked elevations w/ untreated pernicious anemia
• Large elevations with folate deficiency anemia
Isoenzymes of LDH
• LDH-5 (liver, skeletal muscle, skin)
• LDH-3 (lung lymphocytes, spleen, pancreas, placenta, 50% malignancy) “3 cancerous lobes of the lung”
• LDH-1 (heart, RBCs, renal cortex, brain) “1 Red Heart”
Elevation of LDH-1
(“Red Heart”)
• Myocardial infarct*
• Hemolytic anemia*
• Megaloblastic anemia: B12, folate
• Acute renal infarct
• Testicular & ovarian cancer
Elevation of LDH-3
(“3 cancerous lobes of lung”)
• Acute pulmonary infarction
• Advanced cancer
Elevation of LDH-5
(Liver + Skeletal mm)
• Hepatic congestion
• Hepatitis (Acute liver disease)
• Skeletal muscle injury
Elevation of LDH-1 and LDH-5
• Acute MI
• Chronic alcoholism with hepatitis & megaloblastic anemia
Alanine Aminotransferase (ALT) is predominantly found:
Liver
ALT: Test Interference
• Many drugs cause increased ALT levels
ALT: Increased values
• Acute viral hepatitis (ALT>AST)
• Cirrhosis, alcoholic hepatitis, cholestasis (AST>ALT)
• Hepatotoxic drugs
ALT: Decreased
• Vitamin B6 deficiency
Aspartate Aminotransferase (AST) is found in: (4)
• Liver
• Heart
• Skeletal muscles
• RBCs
AST vs. ALT
• AST is more sensitive, but less specific than ALT
Common etiologies for elevated AST
• Heart (acute MI)-Quick rise
• Liver (hepatitis, cirrhosis, congestion, alcohol or drug-induced liver
dysfunction, space occupying lesions, fatty liver, extrahepatic biliary obstruction)
• Skeletal muscle (acute skeletal muscle injury, myositis, muscular dystrophy, surgery)
• RBCs (hemolysis)
• AST:ALT >1 seen in:
Alcoholic cirrhosis, liver congestion, metastatic tumor
AST: ALT <1 seen in:
Acute hepatitis, viral hepatitis, infectious mono
AST: Test Interferences (3)
• Non-fasting
• Hemolysis
• Exercise
AST: Increased Values
• Liver: Hepatitis cirrhosis
• Heart: Acute myocardial infarct
• Skeletal muscle: Trauma, surgery, progressive muscular dystrophy, recent convulsions, primary muscle diseases
• RBCs: Acute hemolytic anemia, megaloblastic anemia
Elevation of both AST and ALT high is indicative of:
Liver disease
AST/ALT Ratio of 2-6 is commonly associated with
Alcoholic liver disease (chronic liver condition)
AST/ALT Ratio: Normal, Abnormal Conditions
• In normal individuals: 1.15
• Ratio of 2-6 commonly associated with alcoholic liver disease (chronic liver cond.)
• Acute viral hepatitis usually associated with low ratios (.5-.8)
AST & ALT: Myocardial Infarction
• AST rises rapidly (4-6 hours after chest pain) 2-10x
• Peak value of AST (24-36 hours) roughly proportional to degree of cardiac damage
• ALT levels within normal limits
AST & ALT: Viral Hepatitis*
• Commonly see 30-50X upper limit of NL*
• Characteristically, ALT higher than AST (Acute)*
AST & ALT: Viral Hepatitis*
• Commonly see 30-50X upper limit of NL*
• Characteristically, ALT higher than AST (Acute)*
AST & ALT: Progressive muscular dystrophy
• AST activity levels increased (CPK)
• Usually normal in neurogenic musculoskeletal disease
AST & ALT: Other Clinical Significance
• Infectious mono (acute) – values 20X upper limit of normal
• Slight or intermediate elevations w/ intra or extra hepatic cholestasis
• Slight increases: Acute pancreatitis, crush muscle injuries, hemolytic disease
• Slight elevations: Alcohol, certain medications
AST & ALT: Other Clinical Significance
• Infectious mono (acute) – values 20X upper limit of normal
• Transferase levels in cirrhosis vary with status of cirrhotic process
• Slight or intermediate elevations with intra or extra hepatic cholestasis
• Acute pancreatitis, crush muscle injuries, hemolytic disease, slight increases
• Alcohol, certain medications à slight elevations
Acute Myocardial Infarction: Signs/Symptoms
• Precordial pain
• Radiating to back, jaw, arm
• Diaphoresis: Excessive sweating
• Sense of impending doom
• Women: nausea, shortness of breath, fatigue, general sense of not feeling*
Acute Myocardial Infarction: Lab Findings
• Pattern of enzyme changes support diagnosis
• EKG changes diagnostic – 50-75% of cases
• Increased ESR
• Leukocytosis-left shift
Acute Myocardial Infarction: CPK
(Quick to rise + quick to go away)
• Normal total CPK high negative predictive value
• First enzyme to rise: Peaks at 18-30 hours
• Isoenzyme: CPK-2 (MB)
• Disadvantage: only present for short time
Acute Myocardial Infarction: AST
(Parallels CPK)
• Fairly quick to rise: Peaks at 24-36 hours
• Elevated in other diseases
Acute Myocardial Infarction: LDH
(Late to the party and late to leave)
• Rises later
• Peaks 48-60 hours
Acute Viral Hepatitis: Types, Symptoms, What Increases
• Type A or B
• Tiredness, weakness, followed by jaundice
• AST & ALT increase
Chronic Hepatitis leads to an increase in: (2)
• Chronic persistent hepatitis – mild increase in AST & ALT
• Chronic aggressive hepatitis – more severe increase
Obstructive Liver Disease: Extrahepatic
• Stone, spasm, stricture of common bile duct
• Carcinoma of head of pancreas
Obstructive Liver Disease (Cholestasis): Extrahepatic
• Stone, spasm, stricture of common bile duct
• Carcinoma of head of pancreas
Obstructive Liver Disease (Cholestasis): Intrahepatic
• Drug toxicity, cancer
Liver Disease: Lab Findings (3)
• Elevated ALP and GGT
• Normal or slight elevation in transaminases
• Possibly elevated LDH
Liver Disease: Hepatitis or Cholelithiasis
ALP: Higher in Cholestasis
GGT: Higher in Cholestasis
ALT: Higher in Hepatitis
AST: Higher in Hepatitis
LDH: Same (Low Levels)
Acute Pancreatitis: Signs/Symptoms
• Severe abdominal pain radiating to back, steadily increasing, occasionally colicky
• Fever 100-102
• Nausea
• Vomiting
Acute Pancreatitis: Lab Findings
• Amylase – rises within 2-12 hours following episode
• Lipase – advantage over amylase for acute pancreatitis (specific;remain elevated for longer)
• Leukocytosis
• Increased or decreased hematocrit
Prostatic Carcinoma: Symptoms
• No symptoms
• Bladder outlet symptoms
• Hematuria: Painless
• Symptoms of metastasis: Bone Pain
Prostatic Carcinoma: Lab Findings
• Hematuria
• Pyuria
• Acid phosphatase: Monitoring tx
• Alkaline phosphatase (mets to bone)
• PSA: Best
Malignancy
• 50% elevated total LDH, LDH-3 isoenzymes
Malignancy
• 50% elevated total LDH, LDH-3 isoenzymes
Hematopoietic Disease: What elevates?
• LDH-1 elevated in hemolytic states
Muscle Disease: What is best for detection/management?
• CPK-3 best test for detection and management