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Biochem 3386 > Enzymes in health and diseas > Flashcards

Enzymes in health and diseas Flashcards

1
Q

Energy depletion as a mechanism leading to the release of cytosolic enzymes:

A

Reduce ATP –>efflux of K+ and influx of Na+ (inhibition of Na-K ATPase –> cell swelling –> reversible damage –> over time: irreversible damage –> influx of calcium and formation of free radicals

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2
Q

Effects of energy depletion

A

Stretching (due to swelling),
Degradation of phospholipids,
Decomposition of the cytoskeleton

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3
Q

Generalized septicemia

A

Irreversible membrane damage causing massive increases in serum enzyme activities

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4
Q

Cell necrosis causes

A

liberation of organelle enzymes

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5
Q

Presence of enzymes in serum is evidence for

A

severe cell injury

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6
Q

Enzymes released from intra–>extracellular space frist appear in…

A

Interstitial fluid

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7
Q

Enzymes released from blood/endothelial cells first appear in

A

Intravascular space

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8
Q

Pathway from interstitial fluid –>blood

A

through LYMPH** OR capillary wall (depends on permeability) ** important part of movement from intracellular–> intravascular space. Not always immediately present in blood as lymphatic flow is slow

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9
Q

Mechanisms of enzyme elimination from the blood (2):

A
  1. Renal excretion (not of general importance as most enzymes are larger than this method supports [ex. ~70-160 kDa])
  2. Uptake by cells that degrade enzymes
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10
Q

Kidney excretion is available for enzymes w/ mw lower than:

A

60 kDa

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11
Q

Mechanism for degradation of enzymes among cells:

A

Receptor mediated endocytosis

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12
Q

Myocardial infarction

A

Heart attack, occlusion of a coronary artery

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13
Q

MI occurs as a result of… (2):

A

lack of O2 delivery to the myocardial tissue

lack of removal of metabolites

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14
Q

MI is influenced by:

A

severity of ischemia (inadequate blood supply),
age,
sex

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15
Q

First few seconds of MI

A

Anoxia –> depletion of energy stores –> OxPhos shutdown –> Anaerobic respiration –> leakage of intracellular electrolytes (espec. K+)

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16
Q

First few minutes (reversible damage)

A

Ischemia –> impaired clearnce of metabolites (ex. inorganic P, lactate, adenosine, H+)

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17
Q

Irreversible damage associated with MI:

A

Release of macromolecules
Activation of lipoprotein lipases
Loss of mitochondrial control
Spillage of mitochondrial components

18
Q

Fate of released cellular components

A

Ions/metabolites: intracellular space –> interstitial space –> circulation
Macromolecules: delayed clearance as they are released only through irreversible injury and are large and require LYMPHATIC DRAINAGE

19
Q

CK equilibrium reaction

A

Creatine + ATP Creatine phosphate + ADP

20
Q

CK

A

important in diagnosis of MI, two subunits either M or B type producing 3 different isoenzymes: BB, MB, and MM

21
Q

Stats on CK

A

High levels in neonate, fall w/in first few wks of life
Total CK is elevated in MI and injury
Males have higher values than females
Activities of CK increase w/ age + body weight

22
Q

Injuries elevating CK

A 
Skeletal muscle injury and disease
IM injections
Hypothyroidism
Generalized convulsions
Cerebral injury
Infectious disease
Prolonged hypothermia
23
Q

CK: MB (CK-2)

A

has advantages over other CK isoenzymes, found in trace concentrations in skeletal muscles and higher in the myocardium

24
Q

CK nomenclature

A

due to electrophoretic mobility, most anodal receiving the lowest number

25
Q

CK: MM (CK-3)

A

found in skeletal muscle and myocardium

26
Q

CK: BB (CK-1):

A

found in the brain and gastrointestinal tract

27
Q

Method of measurement

A

Antibody based CK-MB mass assays (ug/L)

Double monoclonal antibody-based sandwich type assay

28
Q

Lactate dehydrogenase (LD)

A

responsible for catalysing the reversible reduction of pyruvate to lactate
NADH + pyruvate lactate + NAD
late marker of MI as it stays in the blood longer
Important in glycolysis when O2 is limiting
widespread tissue distribution (NONSPECIFICITY)

29
Q

Individuals who exercise heavily have…

A

high LD

30
Q

LD results for MI are obscured by…

A

Hemolysis, due to its presence in red cells

31
Q

The heart contains high amounts of

A

LD1

32
Q

Myoglobin and Troponin

A

cardiac proteins of diagnostic value in MI

33
Q

Myoglobin

A

found in skeletal muscle and heart
does not exist as isoenzymes
low specificity
small size

34
Q

Troponin

A

3 subunits: C, I, and T
Sequence unique to the cardiac muscle (high specificity)
assays have monoclonal antibodies binding to the most stable region of the cTnI molecule
exists in many forms in the blood

35
Q

Biochemical markers in ischemic injury

A

Initial lag phase… and then:
CK: elevates after 20 hours and decreases rapidly (specifically MB), not a good early marker (NOT A GOOD TEST)
Myoglobin: spike 10h after onset and rapid decrease (NOT USED)
TroponinI: longer response time, elevates after 20 hours and stays elevated (GOLD STANDARD FOR MI). Stay elevated. Sensitivity higher, specificity higher.
LD, LD-1: extremely useful late marker due to prolonged half life in serum. LD-1 is better specificity than LD, sensitivity similar in both. A ratio >1 is indicative of MI in LD-1>LD-2. Hemolysis gives a flipped pattern of this (NOT USED ANYMORE)

36
Q

High sensitivity troponins

A

Usually hsTnT
Can measure levels in almost 100% of healthy individuals reliably
10x lower detection limit
Early diagnosis
Problem: number of false positives increases as we move decision threshold to the left, causes other than MI
Rising/falling pattern is critical to distinguish between non-cardiac conditions and acute cardiac conditions

37
Q

Universal definition of MI

A

a rise and or fall in cTn in patients w/ evidence of myocardial ischemia with at least one cTn value above the 99th percentile of reference group

38
Q

Pancreatic enzymes of diagnostic value (2):

A

Amylase

Lipase

39
Q

Acute pancreatitis

A

inflammatory disease of the pancreas which when the attack is resolved permits restoration of normal function
Causes: alcohol, biliary tract disease, post-surgery, and sever hypertriglycerdemia
Symptom: acute abdominal pain, hypotension, respiratory failure, hyperglycemia, hypocalcemia, hypoalbuminemia

40
Q

Amylase

A

highest concentration in saliva and pancreas
secreted into the duodenum –> hydrolysis of macromolecular carbohydrates
Two types: pancreatic type and salivary type, present in about equal concentrations in normal serum and urine
low mw
The only serum enzyme normally found in urine
isoenzyme p-amylase has high sensitivity and specificity

41
Q

Lipase

A

hydrolysing triglycerides
pancreatic isoenzyme interacts with long chain triglycerides
colipase is required for full activity (coenzyme)
Rises to a higher extent than amylase
sensitivity and specificity are higher than amylase

42
Q

Trypsin

A

20-30x more costly than amylase/lipase
similar results to same
not routinely used

Biochem 3386 (14 decks)

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