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Pathophysio > Lab 10. Hepatic enzymes > Flashcards

Lab 10. Hepatic enzymes Flashcards

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1
Q

Types of hepatic enzymes

A
  • Cytoplasmic

- Mitochondrial

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2
Q

Severe liver damage affects elevation of what enzymes?

A

Mitochondrial

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3
Q

Not too severe liver damage affects elevation of what enzymes?

A

Cytoplasmic

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4
Q

AST stands for?

A

Aspartate aminotransferase

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5
Q

AST location?

A

Mitochondria of liver cells, muscles, (heart), RBC (false increase)

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6
Q

AST is liver specific for what species?

A

Herbivores

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7
Q

AST function?

A
  • Converts alpha-keto-glutaric acid to L-glutamic acid

- Converts L-aspartate to oxalic acetic acid

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8
Q

AST basic of measurement method:

A
  • AST enzyme with L-aspartate and alpha-ketoglutarate produces oxalic acetate and L-glutamate.
  • Oxalic acetate with NADH+H+ and malate dehydrogenase (in reagent), produces malate and NAD+
  • NADH+H+ -> NAD+ change causes absorbancy reduction
  • The speed correlates with AST activity
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9
Q

AST, causes of increased activity? From muscle cells

A
  • Intensive exercise
  • training
  • muscle necrosis
  • muscular inflammation (myositis
  • muscle injury (i.m. injection)
  • myocarditis (CK and LDH also increased)
  • neoplasm of muscles (rhabdomyosarcoma, AST/ALT >1)
    In case of muscle cell damage, generally CK and LDH enzymes also are elevated
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10
Q

AST, causes of increased activity? From liver cells

A
  • Ethanol consumption (human being its damaging mitochondria of liver cells, AST/ALT >1)
  • hepatopathy (in herbivores)
  • severe parenchymal damage (in carnivores ex. severe lipotic degeneration, hepatitis or toxic liver damage)
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11
Q

AST, causes of increased activity? From RBCs

A

Hemolysis

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12
Q

AST, causes of decreased activity?

A
  • Metronidasol (antimicrobial drug, cause liver function problems)
  • Vit. B6 deficiency
    (practically no diagnostic importance)
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13
Q

ALT stands for?

A

Alanine aminotransferase

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14
Q

ALT location?

A
  • Cytoplasm of liver cells, RBCs (false increase),
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15
Q

ALT liver specific in what species?

A

Liver specific in carnivores

Not specific in herbivores (small amount found in heart- and striated muscle, kidney cells)

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16
Q

ALT function?

A
  • Converts alpha ketoglutaric acid to L-glutamic acid

- Converts L-alanine to pyruvic acid

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17
Q

ALT basic of measurement method:

A
  • Produced pyruvic acid is converted to lactic acid by lactate dehydrogenase (LDH, in the reagent)
  • This process causes NADH+H+ -> NAD transformation
  • Causes discoloration of a chromophor, and absorbancy reduction
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18
Q

ALT causes of increased activity?

A
  • Liver cell damage (especially in carnivores)
  • chronic active hepatitis (CAH), cholangiohepatitis (CH)
  • virus hepatitis (human) AST/ALT <1
  • hepatic lipidosis
  • cirrhosis
  • bile duct obstruction
  • liver neoplasm (AST/ALT <1)
  • pancreatitis
  • septicaemia
  • neoplasm
  • drugs: barbiturates, glucocorticoids, salicylates, tetracyclines,
  • as a result of cell damage
  • copper storage disorder: Doberman pincher, West highland white and Bedlington terrier
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19
Q

GLDH stands for?

A

Glutamate dehydrogenase

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20
Q

GLDH location?

A

Mitochondria of liver cells, small amount in nerves and muscles

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21
Q

GLDH liver specific in what species?

A

Horses, ruminants and dogs

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22
Q

GLDH function?

A

Binds NH3 to form glutamic acid

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23
Q

GLDH basic of measurement method:

A
  • GLDH converts alpha ketoglutaric acid to L-glutamic acid
  • This process causes NADH+H+ -> NAD
  • Transformation causes discoloration of a chromophor
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24
Q

GLDH causes of increased activity?

A

Severe liver cell necrosis that leads to mitochondrial membrane damage

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25
ALKP stands for, and is a what
AP- alkaline phosphate, it is a bilde duct obstruction enzyme
26
ALKP location?
- Every cell membrane - Produced by diff organs; placenta, bones, hepatocytes, biliary epithelial cells, intestines, kidney tubular epithelial cells - Conversion in bile endothelial cells
27
ALKP, what kind appears in blood?
Only hepatic and bone ALKP appears in blood
28
ALKP liver specific in what species?
Not liver specific in cats (half life is short, excreted in kidney)
29
ALKP isoenzymes:
- Distinction between isoenzymes of bone and liver origin Liver: ALKP is heat stabile Bone: ALKP is heat labile --> heating plasma up to 65C for 5 min inactivates bone ALKP
30
One heat stabile isoenzyme of ALKP?
Steroid induced alkaline phosphatase (SIAP), produced in the liver
31
Isoenzymes of ALKP can be differentiated by what methods?
- Heat test - Electrophoresis - Specific blocking (L-fenylalanine, ELISA, chromatographic)
32
ALKP function?
- pH optimum is 10, so not an active enzyme - Phosphotransferase (not phosphatase) - > generally phosphate esters are translocated to alcohols or phenol hydroxyl groups to another by ALKP
33
ALKP basic of measurement method:
- 4-nitrophenyl phosphate and H2O is converted to 4-nitrophenol and phosphate ion (latter bound to buffer solution used in reagent) - Produced 4-nitrophenol is yellow, detected spectrophotometrically
34
ALKP causes of increased activity? Bone originated
- Young dogs (<8 months) - new born animals - pregnant animals (from bone and placenta) - bone tumors (osteosarcoma) - osteomyelitis - bone fractures - healing of fractures (callus formation)
35
ALKP causes of increased activity? Paraneoplastic processes
- Lymphoid, lung and hepatic tumors
36
ALKP causes of increased activity? Liver originated
- Cholestasis (bilirubin has a direct ALKP increasing effect on the biliary epith. cells) - bile acids (increased synthesis ALKP, and help liberating it from membr.) - acute hepatic necrosis - liver cirrhosis - intra or extrahepatic biliary obstruction - cholangiohepatitis - hepatic lipidosis - barbiturates (increasing synthesis of ALKP) - salicylates (liver cell and biliary epith. cell damage)
37
ALKP causes of increased activity? In connection with increased SIAP synthesis
- Hyperadrenocorticism - iatrogenous (as drug: gluco- or sexual corticoids) - endogenous: Cushings disease - chronic stress
38
ALKP causes of decreased activity?
- Very severe cirrhosis (decreased synthesis) | - practically no diagnostic importance
39
GGT stands for? and its a what
Gamma glutamyl transferase, its a bile duct obstruction enzyme
40
GGT location?
- Produced by diff organs: kidney, pancreas, intestine and liver - endothelial cells of bile duct concentrates it
41
GGT liver specific in what species?
Liver specific in horse and cat
42
What kind of GGT appears in blodd?
Liver origin GGT
43
What causes increased ALKP in urine
Tubular cell damage
44
What causes increased GGT in urine
Tubular cell damage
45
GGT function?
- On the external surface of the cells any of the L-alpha aminoacids can be attached to reduced glutathione, and transported through the membrane by GGT - GGT is bound to glutathione
46
GGT basic of measurement method:
- Synthetic substrate, L-gamma glutamy 4-nitro anilide and glicyl-glicyn is converted to L-gamma glutamyl glicyl-glicyn and 4-nitro anilin by GGT - The former 4-nitro anilin is yellow and can be detected spectrophotometrically
47
GGT causes of increased activity?
- Biliary stasis (cholestasis) - cholangiohepatitis - cirrhosis - neoplasm (hepatic, pancreatic) - hepatic lipidosis - barbiturates - ethanol specifically exaggerates the GGT exertion (human)
48
GGT causes of decreased activity?
- cirrhosis | - practically no clinical importance
49
Other liver specific enzymes:
OCT (ornityl carbamyl transferase), Ar (arginase), SDH (sorbite dehydrogenase)
50
OCT (ornityl carbamyl transferase), Ar (arginase), SDH (sorbite dehydrogenase) are what?
Parenchymal enzymes, their activity increase when there is liver cell damage
51
SDH, liver specific in what species?
Swine, cattle, horse
52
OCT liver specific in what species?
Dogs
53
AR liver specific in what species?
Dogs and horses
54
What to measure? Dog:
ALT (AST, GLDH) ALKP GGT
55
What to measure? Cat:
ALT (AST, GLDH) not routinely measured GGT (ALKP, in acute processes)
56
What to measure? Ruminants:
AST GLDH (GGT) not routinely measured
57
What to measure? Horse:
AST GGT (Ar) not routinely measured
58
What to measure? Swine:
``` AST GGT ALKP OCT SDH ```
59
Examination of change in lipid metabolism due to impaired liver function; cause of decreased total cholesterol conc.
- Decreased esterification ability (decreased cholesterol-ester formation) - Decreased apolipoprotein synthesis (decreased transport of cholesterol due to decreased HDL and LDL synth.)
60
Examination of change in lipid metabolism due to impaired liver function; increased FFA conc. in case of increased energy demand (lipaemia), cause?
Decreased FFA utilization especially in case of increased energy demand
61
Examination of change in lipid metabolism due to impaired liver function; cause of lipid accumulation in liver?
- Decreased ability to perform a beta oxidation (decreased lipid breakdown) - Decreased synth. of lipid-transporting apolipoprotein molecules (decreased HDL, LDL and VLDL synth.)
62
Other diagnostic approaches?
Liver biopsy or aspiration cytology Lipid content evaluation from the liver biopsy sample
63
Liver biopsy or aspiration cytology;
- Routine cytology or histology - Laboratory evaluation of lipid, protein, glycogen etc. content of the liver - Histology approach considered best alternative
64
Lipid content evaluation from the liver biopsy sample; + normal gravity of liver + lipid content normal range
- Pieces of liver biopsy samples into MgSO4 solutions of diff. conc. (MgSO4 dilution scale) - Normal gravity: 1,07-1,08 g/ml - Lipid content: 40-60 g/kg
65
Physiological increase of lipid content in dairy cows, normal range; Gravity
1,04 g/ml
66
Physiological increase of lipid content in dairy cows, normal range; Lipid content
100-120 g/kg
67
Physiological increase of lipid content in dairy cows, normal range; pathological increase of lipid content, gravity
1,01 g/ml
68
Physiological increase of lipid content in dairy cows, normal range; Lipid content
300-400 g/kg
69
Normal value ammonia conc. Dog and Cat
Dog: 26,4-70,5 umol/L Cat: 17,6-58,7 umol/L

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