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MedEd + PathSoc + Laz's Qs + Romesh Path > ChemPath 23: Enzymes and Cardiac Markers > Flashcards

ChemPath 23: Enzymes and Cardiac Markers Flashcards

1
Q

Where are most enzymes found?

A

Intracellularly

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2
Q

What are the two types of intracellular enzymes?

A

Cytosolic

Subcellular (w/in organelles)

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3
Q

Describe the order of release of intracellular enzymes when cells are damaged

A

Cytosolic are released first, followed by subcellular

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4
Q

In which tissues is ALP present in high concentrations?

A

Liver

Bones

Intestines

Placenta

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5
Q

What is an increase in bone ALP caused by?

A

Increased osteoblast activity

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6
Q

What technique is used to separate isoenzymes?

A

Electrophoresis

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7
Q

List some physiological causes of high ALP.

A

Pregnancy – 3rd trimester (from placenta)

Childhood – growth spurt

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8
Q

List some causes of very high ALP (> 5 x upper limit of normal).

A

Bone – Paget’s disease, osteomalacia

Liver – cholestasis, cirrhosis

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9
Q

List some causes of moderately raised ALP (< 5 x upper limit of normal).

A

Bone – tumours, fractures, osteomyelitis

Liver – infiltrative disease, hepatitis

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10
Q

Describe the ALP levels in osteoporosis.

A

It is NORMAL unless there is a fracture

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11
Q

Which markers are used in acute pancreatitis?

A

Amylase

Lipase

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12
Q

Where else is amylase found? - hence what other condition is it raised in ?

A

Salivary glands

NOTE: will be raised in parotitis

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13
Q

What are the three forms of creatine kinase?

A

CK-MM = skeletal muscle

CK-BB = brain

CK-MB = cardiac muscle

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14
Q

Describe the manifestations of statin-related myopathy.

A

Can range from myalgia to rhabdomyolysis

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15
Q

List some risk factors for statin-related myopathy

A

Polypharmacy (particularly fibrates and ciclosporin and other drugs metabolised by CYP3A4)

High dose

Genetic predisposition

Previous history of myopathy

Vitamin D deficiency

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16
Q

List some other causes of high CK

A

Muscle damage

Myopathy (e.g. Duchenne muscular dystrophy)

MI

Severe exercise

Physiological (Afro-Caribbeans)

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17
Q

What are two other uses of enzymes in clinical medicine?

A

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)

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18
Q

List three cardiac enzymes that used to be used as markers of cardiac damage

A

Myoglobin
CK-MB
Troponins

AST, LDH - used in the past but now obsolete

19
Q

Where are myoglobins found within cells?

A

Cytosol

20
Q

Where is CK-MB found within cells?

A

Within the mitochondria and nucleus

21
Q

Where are troponins found within cells?

A

Within the contractile apparatus

NOTE: there is also a free cytosolic pool of troponins

22
Q

Describe how troponin levels change with time following an MI

A

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

23
Q

Outline the diagnostic criteria for MI

A

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
24
Q

How are biomarkers used when deciding whether to thrombolyse?

A

None of the current biomarkers rise quickly enough to aid decisions regarding thrombolysis (so it is based on clinical findings and ECG)

25
Q

What are the main biomarkers used in cardiac failure?

A

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)

26
Q

Define 1 international unit of enzyme activity

A

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)

27
Q

Comparison of Myoglobin, CK-MB and Troponins as cardiac biomarkers

When does it peak?

A

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
28
Q

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?

A

Tea-stained urine = MYOGLOBIN due to rhabdomyolysis of muscle cells being broken down

Blood results usually has raissed CK-MM - often 5x upper limit

29
Q

What marker is raised in the following conditions?

Heart failure
Statin-related myopathy
Muscular dystrophy (Duchenne, Becker)
Myositis (dermato, poly)
Rhabdomyolysis
A

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

30
Q

Which liver enzyme can be measure in blood and specifically suggests obstructive jaundice if levels are raised?

A

Alkaline Phophatase (ALP)

31
Q

What do the following LFT results mean:

ALP + GGT high
ALP > GGT
GGT > ALP

A

ALP + GGT high
- Billiary obstruction (gallstones, pancreatic cancer?)

ALP > GGT

  • Bone problem (osteomalacia, pagets)
  • Pregnancy

GGT > ALP
- Recent alcohol intake

32
Q

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
A

Pagets disease - Normal Ca, phosphate, PTH and High ALP

The rinnes and webers test reveals sensorineural hearing deafness - A feature seen in Pagets

33
Q

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
A

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

34
Q

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
A

Although everything is raised, AST is most raised suggestive of alcoholic cause (alcoholic hep)

Can see AST:ALT ratio 2:1 or

35
Q

What do the following LFT results mean:

AST + ALT are high
AST > ALT
ALT > AST

A 
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)
36
Q

What are the following tumour markers used for?

CA 125
CA 19-9
PSA
CEA
AFP
A

CA 125 - Ovarian cancer

CA 19-9 - Pancreatic cancer, cholangiocarcinoma

PSA - Prostate cancer

CEA - Colorectal cancer

AFP - HCC, Testicular cancer (teratoma)

37
Q

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?

A

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

38
Q

What conditions are the following nuclear medicine imaging tests used for?
Gallium-68-Dotate

A

Gallium-68-Dotate

- Primary NETs (Neuroendocrine tumours) eg insulinoma, gastrinoma

39
Q

What conditions are the following nuclear medicine imaging tests used for?
FDG-PET

A

FDG-PET

- Abdominal mets

40
Q

What conditions are the following nuclear medicine imaging tests used for?
Tech99-sestamibi

A

Tech99-sestamibi

- Parathyroid disease

41
Q

What conditions are the following nuclear medicine imaging tests used for?
MIBG

A

MIBG

- Phaeochromocytomas

42
Q

What conditions are the following nuclear medicine imaging tests used for?
Tec99-pertechnetate

A

Tec99-pertechnetate

- Thyroid disease (eg Graves)

43
Q

What conditions are the following nuclear medicine imaging tests used for?
Tec99-bisphosphonate

A

Tec99-bisphosphonate

- Bone mets + Pagets

MedEd + PathSoc + Laz's Qs + Romesh Path (99 decks)

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