ChemPath 23: Enzymes and Cardiac Markers Flashcards
Where are most enzymes found?
Intracellularly
What are the two types of intracellular enzymes?
Cytosolic
Subcellular (w/in organelles)
Describe the order of release of intracellular enzymes when cells are damaged
Cytosolic are released first, followed by subcellular
In which tissues is ALP present in high concentrations?
Liver
Bones
Intestines
Placenta
What is an increase in bone ALP caused by?
Increased osteoblast activity
What technique is used to separate isoenzymes?
Electrophoresis
List some physiological causes of high ALP.
Pregnancy – 3rd trimester (from placenta)
Childhood – growth spurt
List some causes of very high ALP (> 5 x upper limit of normal).
Bone – Paget’s disease, osteomalacia
Liver – cholestasis, cirrhosis
List some causes of moderately raised ALP (< 5 x upper limit of normal).
Bone – tumours, fractures, osteomyelitis
Liver – infiltrative disease, hepatitis
Describe the ALP levels in osteoporosis.
It is NORMAL unless there is a fracture
Which markers are used in acute pancreatitis?
Amylase
Lipase
Where else is amylase found? - hence what other condition is it raised in ?
Salivary glands
NOTE: will be raised in parotitis
What are the three forms of creatine kinase?
CK-MM = skeletal muscle
CK-BB = brain
CK-MB = cardiac muscle
Describe the manifestations of statin-related myopathy.
Can range from myalgia to rhabdomyolysis
List some risk factors for statin-related myopathy
Polypharmacy (particularly fibrates and ciclosporin and other drugs metabolised by CYP3A4)
High dose
Genetic predisposition
Previous history of myopathy
Vitamin D deficiency
List some other causes of high CK
Muscle damage
Myopathy (e.g. Duchenne muscular dystrophy)
MI
Severe exercise
Physiological (Afro-Caribbeans)
What are two other uses of enzymes in clinical medicine?
Markers of therapeutic response and drug toxicity (e.g. TPMT activity should be measured before starting thiopurines (e.g. azathioprine))
Reagents to measure other substances (e.g. glucose oxidase is used to measure plasma glucose)
List three cardiac enzymes that used to be used as markers of cardiac damage
Myoglobin
CK-MB
Troponins
AST, LDH - used in the past but now obsolete
Where are myoglobins found within cells?
Cytosol
Where is CK-MB found within cells?
Within the mitochondria and nucleus
Where are troponins found within cells?
Within the contractile apparatus
NOTE: there is also a free cytosolic pool of troponins
Describe how troponin levels change with time following an MI
Rise at 4-6 hours post-MI
Peaks at 12-24 hours
Remains elevated for 3-10 days
So, troponins should be measured at 6 hours and 12 hours after the onset of chest pain in a suspected MI
Outline the diagnostic criteria for MI
Typical rise and gradual fall in troponin or more rapid rise and fall in CK-MB with at least one of the following:
- Ischaemic symptoms
- Pathological Q waves
- ECG changes suggestive of ischaemia
- Coronary artery intervention
- Pathological findings of acute MI
How are biomarkers used when deciding whether to thrombolyse?
None of the current biomarkers rise quickly enough to aid decisions regarding thrombolysis (so it is based on clinical findings and ECG)
What are the main biomarkers used in cardiac failure?
ANP – from the atria
BNP – from the ventricles
BNP is used to assess ventricular function and can be used to exclude heart failure (high negative predictive value)
Define 1 international unit of enzyme activity
Quantity of enzyme required to catalyse a reaction of 1 µmol of substrate per minute
NOTE: activity is affected by assay conditions such as pH and temperature (so reference ranges may differ between laboratories)
Comparison of Myoglobin, CK-MB and Troponins as cardiac biomarkers
When does it peak?
Myoglobin:
- Lowest peak (around 8-10 hrs after)
- Shortest 1/2life so good for detecting reinfarcts (multiple MIs in short period)
- Not really used in practice
Myoglobin:
- Lower peak (around 24 hrs after)
- Next shortest 1/2life so good for detecting reinfarcts (multiple MIs in short period)
- Not really used in practice
Troponins:
- Peak 24-48 hrs
- Most sensitive and speciifc test
- Ideally measure at 6 hrs and 12 hrs post MI for best sensitivity and specificity
An 80 year old man was taken to A&E by his carers after they found him on the floor. He said he couldn’t get up after falling, and was on the floor for 18 hours. On examination, he had dry mucous membranes, low skin turgor and dark ‘tea-stained urine’. Microscopy of the urine did not identify red blood cells.
Urine dip = Blood +ve
What substance causes the urine to be ‘tea-stained’ in colour?
Which enzyme would be raised in their blood results + how high?
Tea-stained urine = MYOGLOBIN due to rhabdomyolysis of muscle cells being broken down
Blood results usually has raissed CK-MM - often 5x upper limit
What marker is raised in the following conditions?
Heart failure Statin-related myopathy Muscular dystrophy (Duchenne, Becker) Myositis (dermato, poly) Rhabdomyolysis
Heart failure - Raised BNP
Statin-related myopathy - Raised CK-MM
Muscular dystrophy (Duchenne, Becker) - Raised CK-MM
Myositis (dermato, poly) - Raised CK-MM
Rhabdomyolysis - Raised CK-MM
Which liver enzyme can be measure in blood and specifically suggests obstructive jaundice if levels are raised?
Alkaline Phophatase (ALP)
What do the following LFT results mean:
ALP + GGT high
ALP > GGT
GGT > ALP
ALP + GGT high
- Billiary obstruction (gallstones, pancreatic cancer?)
ALP > GGT
- Bone problem (osteomalacia, pagets)
- Pregnancy
GGT > ALP
- Recent alcohol intake
An 82 year old man has a 3 month history of progressive deafness (sensorineural)
Weber’s test – lateralisation of vibration to the left ear
Rinne’s test – AC > BC in both ears
Blood results are: Normal Ca, Phosphate, PTH and Raised ALP
What is the most likely underlying diagnosis?
- Osteomalacia
- Primary hyperparathyroidism
- Paget’s disease
- Tertiary hyperparathyroidism
- Osteoporosis
Pagets disease - Normal Ca, phosphate, PTH and High ALP
The rinnes and webers test reveals sensorineural hearing deafness - A feature seen in Pagets
60 year old man with a BMI of 28 was referred with abdominal pain. His LFTs are:
Raised BR, ALP, AST, ALT, GGT and CK
ALP is raised more than other markers
What is the most likely diagnosis?
- Acute pancreatitis
- Alcoholic cirrhosis
- Viral hepatitis
- Haemolytic jaundice
- Obstructive jaundice due to gallstones
Although everything is raised, ALP is most raised suggestive of an obstructive cause
BMI is high (RF) and has referred abdo pain
All these findings point towards obstructive jaundice due to gallstones
60 year old man with a BMI of 28 was referred with abdominal pain. His LFTs are:
Raised BR, ALP, AST, ALT, GGT and CK
AST is raised more than other markers
What is the most likely diagnosis?
- Acute pancreatitis
- Alcoholic cirrhosis
- Viral hepatitis
- Haemolytic jaundice
- Obstructive jaundice due to gallstones
Although everything is raised, AST is most raised suggestive of alcoholic cause (alcoholic hep)
Can see AST:ALT ratio 2:1 or
What do the following LFT results mean:
AST + ALT are high
AST > ALT
ALT > AST
AST and ALT are high: Hepatocyte damage (e.g. hepatitis)
AST > ALT: Alcoholic hepatitis (S for Smirnoff) - 2:1 ratio or greater often
ALT > AST: Viral hepatitis (L for ViraL)
What are the following tumour markers used for?
CA 125 CA 19-9 PSA CEA AFP
CA 125 - Ovarian cancer
CA 19-9 - Pancreatic cancer, cholangiocarcinoma
PSA - Prostate cancer
CEA - Colorectal cancer
AFP - HCC, Testicular cancer (teratoma)
A man presents with a swollen, inflamed metatarsal joint. A needle aspirate is performed with microscopy identifying needle shaped crystals with negative birefringence.
Which enzyme manufactures the material that makes up the crystal? mx of this condition?
Negativ birefringence = Gout - the enzyme responsible is Xanthine Oxidase
This is why the treatment of gout can involve the use of Xanthine Oxidase inhibitors such as Allopurinal
What conditions are the following nuclear medicine imaging tests used for?
Gallium-68-Dotate
Gallium-68-Dotate
- Primary NETs (Neuroendocrine tumours) eg insulinoma, gastrinoma
What conditions are the following nuclear medicine imaging tests used for?
FDG-PET
FDG-PET
- Abdominal mets
What conditions are the following nuclear medicine imaging tests used for?
Tech99-sestamibi
Tech99-sestamibi
- Parathyroid disease
What conditions are the following nuclear medicine imaging tests used for?
MIBG
MIBG
- Phaeochromocytomas
What conditions are the following nuclear medicine imaging tests used for?
Tec99-pertechnetate
Tec99-pertechnetate
- Thyroid disease (eg Graves)
What conditions are the following nuclear medicine imaging tests used for?
Tec99-bisphosphonate
Tec99-bisphosphonate
- Bone mets + Pagets
