enzymes and cardiac markers Flashcards by Emily Southall

definition of an enzyme

a substance (usually a protein) that increases the rate of a chemical reaction without itself being changed in the overall process

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what is Km

The Michaelis-Menten constant or Km = [substrate] at which the reaction velocity is 50% of the maximum.

high Km indicates weak binding
low Km indicates strong binding.

Black needed 1 unit to reach Vmax
Red needed 5 units to reach Vmax

Lower the Km the better

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what is Km

The Michaelis-Menten constant or Km = [substrate] at which the reaction velocity is 50% of the maximum.

high Km indicates weak binding
low Km indicates strong binding.

Black needed 1 unit to reach Vmax
Red needed 5 units to reach Vmax

Lower the Km the better

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what do elevated serum enzymes suggest

diseased organ - because released in response to cellular injury eg:
* Infection (viral, bacterial, fungal)
* Immune mediated/inflammation (hypersensitivity reactions), e.g., T1DM, Asthma, Rheumatoid arthritis
* Ischaemia (MI, Stroke, ischaemic colitis/hepatitis, haemorrhage)
* Inherited
* Trauma
* Toxins (medications, recreational drugs, alcohol)
* Tumour

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how do you know which organ the marker is coming from

clinical context
or enzyme released predominantly by one tissue

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biochemical markers used for screening

faecal immunochemical test for Bowel cancer;
midnight salivary cortisol or 24-hour urine cortisol for suspected Cushing’s;
TSAT for haemachromatosis,
pre-natal screening tests for down’s syndrome (^hCG, inhibin A, decreased AFP unconjugated oestriol)

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what can biochemical tests be used to help with

screening
dx
response to rx- -eg cholesterol levels after starting statins
long term monitoring - AFP in after surgery for liver cancer, HbA1c for Diabetes,

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what is isoenzyme testing

An isoenzyme are a group of enzymes that perform the same function but they each group has a slightly different structure, which can be picked up by testing.

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what organs produce ALP

intrahepatic or extrahepatic bile ducts
bone
placenta
intestine

-ALP has 4 isoenzymes in 4 different organs, so in each organ ALP carries out the same function but it has a slightly different structure in each organ

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bone causes for raised ALP

Fracture,
Paget’s disease,
Osteomalacia, Rickets,
cancer (primary or metastasis),
1o hyperparathyroidism with bone involvement,
renal osteodystrophy
Childhood (physiological)

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placenta causes of high ALP

Pregnancy (last trimester) - placenta produces ALP - so increases as placenta gets bigger = physiological
Germ-cell tumours

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approach to raised ALP

Check LFTs
If LFTs normal, check Vitamin D - if low = reduced absorption of phos from gut -> break down bone to release phosphate, ALP will remove phos from the bone matrix; (low phosphate stimulates 1a renal hydroxylase producing calcitriol and inhibition of FGF23, thereby increasing serum phosphate)

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describe the age changes of ALP

At birth, ALP is high because of bone growth, ALP then plateaus until just before puberty in boys and girls and falls to adult levels when bone growth ceases

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use of ALT and AST clinically

Used when liver disease is suspected

ALT more specific for liver - but both ALT and AST basically give the same info

AST can come from heart, liver, skeletal muscle or kidney

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hepatic causes of raised ALT

Toxins (Alcohol, paracetamol OD)
Hepatitis (viral, alcohol, autoimmune) Non-alcoholic fatty liver disease
Cancer
Ischaemia

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biomarkers for kidney damage

creatinine
eGFR
albuminuria

biomarkers for pancreatitis

amylase

biomarkers for MI

troponin

what organs is GGT used for

found in liver, biliary system, pancreas and kidneys but it is most clinically useful in hepatobiliary disease

γ-GT is elevated in both hepatic and biliary disease so it is important to check whether the ALT and ALP predominate as this will suggest whether hepatic or obstructive liver disease is more likely

hepatobiliary causes of raised GGT

Hepatitis,
alcoholic liver disease,
cholestatic liver disease

how do drugs caused raised GGT

GGT synthesis is raised in response to:
* alcohol
* rifampicin
* old anti-epileptic drugs (phenytoin, phenobarbitone)

ie more of the enzyme is released from normal cell turnover due to enzyme induction

what organs/cells produce LDH

WBC
RBC
placenta
skeletal muscle
liver injury
cardiac

plays an important role in anaerobic metabolism and hence it is found in blood cells which do not contain a mitochondria and therefore rely on anaerobic metabolism and also found in muscle cells

causes of raised LDH

haemolytic anaemia - high LDH, low haptoglobin, high K and phos and bilirubin

elevated LDH as a px marker

Elevated LDH in patients with lymphoma or a germ cell testicular cancer is associated with poor prognosis and is associated with tumour bulk

so patients on treatment will have serial LDH to assess response to treatment

– the higher the LDH, the bigger the tumour – monitor when put people into remission

organs that have amylase

pancreas salivary gland if high - think abdo path *Elevated levels also seen in something called ‘macro-amylase’ which can happen with other proteins such as CK where an immunoglobulin binds to the protein so it is not cleared and it remains elevated for some time and can cause confusion - persistently high, but benign. But in this situation, request electrophoresis for iso-enzymes*.

pancreas causes of high amylase

**Acute pancreatitis**, perforated duodenal ulcer, bowel obstruction (causes secondary injury to pancreas)

salivary gland causes of high amylase

Stones, infection (e.g., mumps)

organs that have creatine kinase

Skeletal muscle cardiac muscle *used to remove phosphate to allow energy metabolism*

skeletal muscle causes of high creatine kinase

Rhabdomyolysis - massive amounts of CK released. Myoglobin can dislodge in kidney -> acute tubular necrosis Myositis, polymyositis, dermatomyositis, severe exercise, myopathy (Deuchene muscular dystrophy, statins) - acute rise *slightly higher levels in individuals of Afro-Carribean descent

use of troponin

in cardiac and skeletal myocytes - used in muscle contraction History + exam + ECG + Troponin = diagnosis Factors affecting troponin result: Age, gender, acute or chronic kidney disease because clear less trop from plasma so have higher levels, number of myocytes injured, time of test.. Troponin T, I, C in heart and skeletal muscle but the assay we use **measures cardiac specific TnI**

causes of elevated troponin

when do you measure troponin

two troponin measurements, **one on admission and another 1 hour later**, and if there is a 50% increase or decrease then this is highly suggestive of dynamic cardiac myocyte injury trop 1 rises in 2-4 hr from chest pain onset within a few hours , there is an exponential increase Trop I remains elevated for 5-10 days

when do you measure troponin

pathway for cardiac chest pain

STEMI = cardiac sounding chest pain + ST elevation show urgently to a senior (needs urgent IP cardio review) don’t wait for troponin NSTEMI = cardiac sounding chest pain + abnormal ECG + elevated troponins -> urgent senior review (will probably need IP cardio review) Unstable angina = cardiac sounding chest pain + normal ECG or ST depression or T wave inversion with normal troponins -> urgent senior review, high risk for progression to MI (needs urgent IP cardio review). Angina = Exertional chest pain relieved by rest or GTN + normal resting ECG + two troponin results that are within the reference range and there is not a 50% change in the results, senior review and probably discharge with outpatient cardiology fu non-specific chest pain, a normal ECG and troponin is unlikely to have cardiac chest pain – negative predictive value is good

pathology of STEMI

acute total occlusion of a coronary artery needs to be opened so blood can perfuse the heart to avoid heart failure. Full thickness necrosis of the cardiomyocytes. subendocardial and myocardium that has ischemia

pathology of NSTEMI

**partial occlusion** so some blood can perfuse the heart so there is partial cardiomyocyte necrosis, which if left untrated can progress to a STEMI. **Just the subendocardial layer that has ischmia**

what are we measuring with BNP

Pro-BNP has a c and N Terminal broken into BNP and NTproBNP Cardiac myocytes are stretched – gene transcription increase within an hour BNP goes to kidneys -> pee a lot, naturisis, half life short So measure NT-proBNP produced in equimolar as BNP – **half life of 3hrs** If don’t get BNP in max 6hrs - will get incorrect result So in GP measure NT-proBNP some drugs for heart failure break down BNP - so another reason to measure NTproBNP

HF dx guidelines

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enzymes and cardiac markers Flashcards

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