enzymes

coronary heart disease

myocardial infarction, chest pain, heart failure, sudden cardiac death

cerebrovascular disease

stroke

transient ischemic attack

peripheral artery disease

intermittent claudication

acute localized pain in the arms and legs

aortic atherosclerotic

aneurysms

dissection

ischemia

lack of adequate blood supply to the heart

-suddensevere blockage leads to heart attack

stable angina

activity related chest pain

stops after activity ends

acute coronary syndrome

-unstable angina has normal biomarkers

-AMI has elevated biomarkers

how is an ACS treated

vasodilators

symptoms of a myocardial infarction

pressure

tightness

pain

nausea

indigestion

shortness of breath

cold sweat

atherosclerosis is chronic or acute

chronica

atherosclerosis is due to

progressive accumulation of lipids, smooth muscle cells, macrophages, and connective tissue with medium-large arteries

principle of serum biomarker of cardiac damage

cell death releases intracellular proteins from the myocardium into blood circulation

Aspartate Transaminase (AST)

cardiac biomarker

-high false negative

-short elevation window for evaluation

Lactate Dehydrogenase (LD)

cardiac biomarker

-more sensitive

-remains elevated for 2 weeks

-low cardiac specificity

LD1 is specific to

myocardium

If LD1 surpasses LD2, what is suspected

a myocardial event

Creatine Kinase (CK)

cardiac biomarker

-highly sensitive after muscle injury

-3 isoforms (muscle, brain, cardiac muscle)

CK is found

in nearly all cells of the body, involved in phosphate production especially for striated muscle

what causes an increase in plasma CK

damage to muscle or brain

CK levels to correlate with myocardial infarction

over 2X the normal value

Creatine Kinase MB

highly specific to myocardial damage, rapidly elevated post MI

-at one point is the most reliable

Myoglobin

iron and oxygen binding protein found exclusively in muscle, absent in circulation

-released quickly when muscle is damaged

-short half life of 9min

-not cardiac specifc, also increases with skeletal muscle damage

cardiac troponin

normally found in muscle tissue

-complex regulates calcium deprendent interactions of myosin heads with actin filaments during striated muscle contraction

Three protein complexs of troponin

-Troponin T (TnT) binds troponin complex to tropomyosin

-Troponin I (TnI) inhibits binding of actin and myosin

-Tropoin C (TnC) binds to calcium to reverse TnI inhibition

Female Troponin levels

Normal= less than 0.013

Abnormal= over 0.013

Critical= Over 0.1

Male Troponin ranges

Normal= less than 0.033

Abnormal= over 0.033

Critical= over 0.1

What is high sensitivity troponin

-has increased sensitivity so it makes MI identification faster

-detects much lower concentrations of troponin proteins

H-FABP

-heart type fatty acid binding protein

-similar to myoglobin but more in heart

-sensitivity about same or higher than cTnT

-specificity lower than cTnT

IMA

-ischemia modified albumin

-doesnt detect myocardial tissue damage

-measures changes in albumin in circumstance of ischemia

BNP is a marker for

heart failure

BNP

-increased pressure and volume load releases natiuretic peptide from the heart which reduces intravascular volume

-identifies if cardiac problem is associated with shortness of breath

BNP precursor

N-terminal pro B type natiuretic Peptide

-released by myocardial cells in response to increased volume increased pressure and cardiac hypertrophy

BNP has a direct correlation with

heart failure severity

C reactive protein (CRP)

-systemic inflammation

-Prognostic because CRP levels in healthy people help evaluate the risk of a first MI

Homocysteine

-if mildly elevated there is CVD risk

-if extremely elevated links to CVD diagnosis

what is a pulmonary embolism

-saddle embolus formation that causes circulation block

-increased heart failure risk, cardiovascular collapse, sudden death

therapy for pulmonary embolism

Low molecular weight heparin

Unfractionated heparin

Long term oral vitamin K

Pulmonary Embolism biomarkers

D dimer

Troponin and BNP

D-dimer

-indirect marker of coag and fibrinolysis

-presence in bloodstream correlates to recent coagulation

-most useful for ruling out pulmonary embolism

Troponin and BNP used in pulmonary embolism by

being used as predictors of adverse outcomes

kidney disease biomarkers

troponin

troponin for kidney disease

prognostic

-increased levels associated with worse long term chronic problems in the absence of an AMI

-with dialysis and increased cTnT is associated with more mortality

congestive heart disease biomarkers

CRP

Homocysteine

Heart failure biomarkers

BNP

cardiac damage biomarkers

AST

LD

CK

Myoglobin

Troponin

H-FABP

IMA

factors that influence enzymatic reactions

substrate concentration

enzyme concentration

pH

temperature

cofactors

inhibitors

enzyme activity is expressed in

international units

-the amount of enzyme that would convert 1 micromole of substrate to product per minute under standard conditions

4 common characteristics of enzymes

-activation energy is lower

-rate of reaction increases

-reaction reaches equilibrium

-enzyme is not consumed in the reaction

3 mechanisms that can lead to increased serum enzymes

-release of enzyme from dead cells

-leakage from cells with altered membrane permeability (hemolysis)

-increased production and secretion by cells

creatine kinase function (CK)

-associated with ATP regeneration in contractile or transport systems

-storage of high energy creatine phosphate

CK tissue source

skeletal muscle

heart muscle

brain tissue

CK diagnostic significance

acute MI

muscular dystrophy

hypothyroidism

reyes syndrome

CK assay enzyme activity

catalyzes both the forward and reverse reaction involving the phosphorylation of creatine or ADP

CK assay errors

hemolysis

serum should be stored in dark place

CK reference range

M= 46-171

F= 34-145

Lactate Dehydrogenase tissue source

heart

liver

skeletal muscle

kidney

erythrocytes

LD diagnostic significance

pernicious anemia

hemolytic disorders

viral hepatitis

cirrhosis

acute MI

skeletal muscle

leukemia

LD assay for activity

catalyzes interconversion of lactic and pyruvic acids using NAD in either forward or reverse

LD reference range

123-220

in most enzyme reaction assays what is the biggest source of error

hemolysis

Aspartate Aminotransferase (AST) tissue source

cardiac tissue

liver

skeletal muscle

AST diagnostic significance

hepatocellular disorders

skeletal muscle

pulmonary embolism

AST assay is based on

karmen method

AST reference range

5-35

Alanine aminotransferase (ALT) tissue source

liver

ALT diagnostic significance

hepatic disorders

ALT assay

coupled enzymatic reaction using lactate dehydrogenase as indicator which catalyzes reduction of pyruvate to lactate with simultaneous oxidation of NADH

ALT reference range

7-45

Alkaline Phosphatase requires

Magnesium as an activator

what is an example of a nonspecific enzyme

Alkaline phosphatase

Alkaline phosphate tissue source

highest concentration in tissue and liver

bone

spleen

placenta

kidney

Alkaline phosphatase diagnostic significance

liver and bone disorders

-hepatobilliary is very elevated

-hepatitis and cirrhosis slight increase

ALP bone disorder highest increase is seen in

Pagets disease / osteitis deformans

ALP assay methods

-direct immunochemical

-electrophoresis

-phenylalanine inhibition

-heat activation where placental ALP is heat stable and bone is heat labile

ALP enzyme activity

catalyzes the reaction of p-nitrophenyl phosphate to p-nitrophenol plus phosphate at a pH of 10.2

ALP reference range

42-128

Acid phosphatase (ACP) physiology

-mostly in prostate

-bone liver, spleen, kidney, RBC, platelets

ACP diagnostic significance

-historically used for detection of prostate cancer but only detectable after metastisized so PSA better

-bone disease

-breast cancer

-hairy cell leukemia

-seminal fluid and sexual assault

Gamma glutamyl transferase (GGT) tissue source

kidney

brain

prostate

-pancreas

-liver

GGT diagnostic significance

hepatobilliary disorders

-billiary obstruction

-alcohol

-diabetes mellitus

-MI

GGT reference range

M= 6-55

F= 5-38

Amylase

catalyzes the breakdown of starch and glycogen

-requires Ca and Cl

-end products are glucose, maltose and dextrins

-smallest enzyme

amylase tissue source

acinar cells of pancreas and salivary glands

amylase is filtered by

renal glomerulus

-only common enzyme in urine, and it remains elevated longer in urine than serum

amylase diagnostic significance

acute pancreatitis

-rise 2-12hrs after onset of attack and then peak 24hrs. normal in 3-5 days

-pancreatic duct obstruction

-opiate use

-mumps

Amylase assay methods

-amyloclastic measures disappearence of starch substrate

-saccharogenic measures appearence of starch and maltose

-chromolytic measures increasing color

Amylase reference range

Serum= 28-100

Urine= 1-15

Lipase

hydrolyzes the ester linkages of fats to produce alcohols and fatty acids

lipase tissue source

pancreas mostly

-stomach and small intestines

Lipase diagnostic significance

-acute pancreatitis

-more specific than amylase

-elevated for about 5 days in acute pancreatitis

Lipase assay methods

turbidometric

lipase reference range

less than 38

Glucose 6 Phosphate Dehydrogenase (G6PD) tissue source

adrenal cortex

spleen

thymus

lymph nodes

lactating mammary gland

erythrocytes

G6PD diagnostic significance

-deficiency is inherited but results in hemolytic anemia, megaloblastic anemia, myocardial infaction

G6PD assay

a red cell hemolysate is used to assay for deficiency of enzyme

-serum is used for evaluation of elevated levels

G6PD reference range

7.9-16.3

PSA diagnostic significance

screening marker for prostate cancer

-measures therapeutic response as well

-should be undetectable with treatment, if still there it has metastisized