● Isoenzymes of CK and their locations

○ CK-BB – brain (can also be found in smooth muscles like the uterus)
○ CK-MB – mostly cardiac muscle;
○ CK-MM – both skeletal and cardiac muscle (striated muscle)

● How to diagnose acute pancreatitis?

○ Serum amylase and serum lipase can be used as markers for acute pancreatitis,
with serum lipase being a better first-line test as it is less affected by other
intra-abdominal conditions as compared with serum amylase
○ However, it is important to note that serum amylase and lipase elevations are not
specific to acute pancreatitis. Hence, other criteria must be checked first before
giving a definite diagnosis:
■ Aside from serum lipase and amylase > 3x of normal upper limit
■ Patient must be having consistent abdominal pain with the disease
■ Characteristic findings from abdominal imaging

● Differentiate hyperamylasemia from macroamylasemia

○ Hyperamylasemia refers to increased serum amylase levels while
macroamylasemia refers to the combining of amylase with immunoglobulins such
as IgG and IgA or polysaccharides to form a complex that is large enough to not
be filtered by the glomerulus
○ In terms of diagnosis, hyperamylasemia, pancreatic hyperamylasemia in
particular, is characterized by high levels of serum amylase, urinary amylase,
amylase clearance to creatinine kinase clearance ratio, but with absent serum
macroamylase
○ Meanwhile, macroamylasemia is characterized by high serum amylase and
serum macroamylase, but low amylase clearance to creatinine kinase clearance
ratio and urinary amylase due to the fact that it cannot be filtered in the renal
system because of its large size

● Compare and contrast serum amylase and serum lipase as diagnostic tests
○ Both serum amylase and serum lipase can be used as markers for acute
pancreatitis. However, serum lipase is a better first-line test as it is less likely to
be affected by other intra-abdominal conditions as compared with serum amylase
○ Amylase is a non-specific marker -- increasing during disorders with both
pancreatic and salivary involvement. Since lipase remains normal in salivary
disorders, lipase can aid in the differentiation between serum amylase elevation
due to pancreatic disorders and due to salivary disorders

● Reason why EDTA, citrate, and oxalate not allowed as anticoagulant in amylase
testing
○ EDTA, Citrate, and oxalate are anticoagulants that are calcium chelators,
meaning they bind with calcium to form calcium salts and prevent coagulation.
These anticoagulants are not used for amylase testing because amylase requires
 calcium for its activation. The presence of these anticoagulants may interfere with
amylase activity and may possibly cause falsely low results.

● Duchenne muscular dystrophy, inheritance, and manifestations

○ DMD is that most common hereditary neuromuscular disease with an X-linked
recessive inheritance pattern
■ Males: 1 mutated gene is enough to cause disease (only 1 X
chromosome)
■ Females: 2 mutated genes to cause disease (2 X chromosomes)
■ Males are more likely to be affected
■ Carrier mother: 50% of passing it to son
■ Carrier father: not pass it to his sons but all daughters will be carriers
○ Characterized by non-inflammatory progressive weakness and degeneration of
the skeletal muscle that controls movement
■ Delayed motor and speech development (takes long to learn to sit, stand,
and walk)
■ Enlarged calf muscles
■ Progressive enlargement of the heart and cardiomyopathy
■ Waddling gait
■ Elevated serum CK
■ Atrophy of both skeletal and health muscle
■ Cognitive impairment
○ Genetic cause: mutation of the dystrophin gene

● Pathophysiology of Duchenne muscular dystrophy

○ Dystrophin is a critical component of the dystrophin-glycoprotein complex which
serves as an important structural component of muscle fibers. This complex
primarily functions to stabilize that plasma membrane.
■ In DMD, dystrophin proteins are mutated; hence, compromising the
integrity of the dystrophin-glycoprotein complex, and in turn, the plasma
membrane of muscle fibers
○ During muscle contractions, stress is exerted on these compromised or fragile
membranes, leading to dysregulation of calcium homeostasis, oxidative damage,
and eventually muscle cell necrosis.
○ The regenerative capacity of muscles will soon be exhausted, and muscle fibers
are gradually replaced with connective and adipose tissue

● Normal skeletal muscle biopsy vs skeletal muscle with Duchenne muscular

dystrophy
○ Muscle biopsy shows: endomysial connective tissue proliferation, scattered
degeneration, muscle fiber necrosis with mononuclear cell infiltrate, and
replacement of muscle with adipose tissue and fat
○ EARLY IMAGING: show only variations in muscle fiber sizes with focal areas of
degenerating or regenerating fibers
 ○ LATER IMAGING: marked variations in muscle fiber sizes, degeneration, and
regeneration. Rounded opaque fibers, internal nuclei, splitting of fibers, and a
proliferation of connective and adipose tissues are also present. As the disease
progresses, fewer and fewer regenerative fibers are seen. In the end phase, the
muscle is mostly replaced by adipose tissue, with residual islets of muscle fibers
in a sea of fat.

● Blood chemistry test ordered in Duchenne muscular dystrophy

○ First test: CK test because it is an enzyme in muscle cells
■ Duchenne: 50-200 fold above normal levels
■ Normal: 200 units/L
○ Chronic damage to muscle causes more persistent elevation of CK
■ Broad range of normal values can hamper recognition of mild, ongoing
muscle injury
■ Congenital myopathies (like Duchenne muscular dystrophy) common
cause of chronic muscle injury
○ The multiplex polymerase chain reaction (PCR) assay may be useful.
■ The PCR method rapidly screens for deletions of the dystrophin gene by
applying PCR to amplify the DNA in the hot-spot regions and by
simultaneously using a number of appropriate primers that flank these
 hot-spot regions. PCR can be used to detect more than 98% of existing
deletions, and it can be performed within 24 hours.

● Chemical reaction catalyzed by CK and its importance

○ Creatine kinase catalyzes the reversible transfer of phosphate between creatine
and ATP or ADP. This reversible reaction results in regeneration of
phosphocreatine when ATP is abundant and regeneration of ATP when ATP is
low.

● CK isoenzymes
○ Cytosolic form has two major isoenzymes: M and B, each of which has the same
activity
○ CK1 or CK-BB: brain
○ CK2 or CK-MB: (hybrid) mostly in cardiac muscles
○ CK3 or CK-MM: (muscle type) in both skeletal and cardiac muscles

● Why is serum CK-BB normal in patients with stroke?

○ Stroke is a serious life-threatening medical condition that happens when the
blood supply to part of the brain is cut off.
■ There are two main causes of stroke: a blocked artery (ischemic stroke)
or leaking or bursting of a blood vessel (hemorrhagic stroke). Some
people may have only a temporary disruption of blood flow to the brain,
known as a transient ischemic attack (TIA), that doesn't cause lasting
symptoms
■ CK-MB NOT CK-BB
● Serum creatine kinase activity in the elderly following a stroke:
They all had positive skeletal (MM) muscle isoenzyme, and in only
one patient heart (MB) isoenzyme was detected. None of them
had positive brain (BB) isoenzyme.
●
○ Because stroke normally affects the central nervous system, and CK-BB is found
in high concentration in the Central nervous system. (Basig naa pa mo ma add)
○ based sa trans: Firstly, most techniques cannot detect CK-BB. Secondly,
because of the large molecular size of CK-BB, it cannot cross the blood-brain
barrier thus serum CK-BB will not elevate despite brain injury. CK-BB is only
detected in the serum if the blood brain barrier loses its integrity because of
extensive damage (ischemic stroke, for example source)

● Blood chemistry tests for AMI diagnosis, time of elevation peak and disappearance in the
serum; sensitivity and specificity of each blood test
○ CK-MB: Begin to rise 4-8 hours after onset of disease. Peak at 12-24 hours.
Return to normal after 48-72 hours.
LDH-1 (HHHH): rises within 12-24 hours. Peaks within 48-72 hours. Remains
elevated for 10 days.
 ● LDH flipped pattern; how does it happen
○ Normally, LDH-2 is the major isoenzyme of LDH
○ However, in heart and red blood cells, LDH-1 is normally present in higher levels
than LDH-2
○ In cases of acute myocardial infarction and intravascular hemolysis, LDH-1 is
released into the serum, increasing the overall LDH-1 levels
○ As a result, LDH-1 will predominate over LDH-2 in the serum; thus, having an
LDH flipped pattern.

● Effect of hemolysis to LDH level

○ Since our erythrocytes contain LDH approximately 100-150 than found in serum,
any degree of hemolysis causes a false elevation in LDH.

https://www.ncbi.nlm.nih.gov/books/NBK482346/