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Pathophysio > Lab 10. Hepatic enzymes > Flashcards

Lab 10. Hepatic enzymes Flashcards

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
Q

ALKP stands for, and is a what

A

AP- alkaline phosphate, it is a bilde duct obstruction enzyme

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26
Q

ALKP location?

A
  • Every cell membrane
  • Produced by diff organs; placenta, bones, hepatocytes, biliary epithelial cells, intestines, kidney tubular epithelial cells
  • Conversion in bile endothelial cells
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27
Q

ALKP, what kind appears in blood?

A

Only hepatic and bone ALKP appears in blood

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28
Q

ALKP liver specific in what species?

A

Not liver specific in cats (half life is short, excreted in kidney)

29
Q

ALKP isoenzymes:

A
  • 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
Q

One heat stabile isoenzyme of ALKP?

A

Steroid induced alkaline phosphatase (SIAP), produced in the liver

31
Q

Isoenzymes of ALKP can be differentiated by what methods?

A
  • Heat test
  • Electrophoresis
  • Specific blocking (L-fenylalanine, ELISA, chromatographic)
32
Q

ALKP function?

A
  • 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
Q

ALKP basic of measurement method:

A
  • 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
Q

ALKP causes of increased activity? Bone originated

A
  • 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
Q

ALKP causes of increased activity? Paraneoplastic processes

A
  • Lymphoid, lung and hepatic tumors
36
Q

ALKP causes of increased activity? Liver originated

A
  • 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
Q

ALKP causes of increased activity? In connection with increased SIAP synthesis

A
  • Hyperadrenocorticism
  • iatrogenous (as drug: gluco- or sexual corticoids)
  • endogenous: Cushings disease
  • chronic stress
38
Q

ALKP causes of decreased activity?

A
  • Very severe cirrhosis (decreased synthesis)

- practically no diagnostic importance

39
Q

GGT stands for? and its a what

A

Gamma glutamyl transferase, its a bile duct obstruction enzyme

40
Q

GGT location?

A
  • Produced by diff organs: kidney, pancreas, intestine and liver
  • endothelial cells of bile duct concentrates it
41
Q

GGT liver specific in what species?

A

Liver specific in horse and cat

42
Q

What kind of GGT appears in blodd?

A

Liver origin GGT

43
Q

What causes increased ALKP in urine

A

Tubular cell damage

44
Q

What causes increased GGT in urine

A

Tubular cell damage

45
Q

GGT function?

A
  • 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
Q

GGT basic of measurement method:

A
  • 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
Q

GGT causes of increased activity?

A
  • Biliary stasis (cholestasis)
  • cholangiohepatitis
  • cirrhosis
  • neoplasm (hepatic, pancreatic)
  • hepatic lipidosis
  • barbiturates
  • ethanol specifically exaggerates the GGT exertion (human)
48
Q

GGT causes of decreased activity?

A
  • cirrhosis

- practically no clinical importance

49
Q

Other liver specific enzymes:

A

OCT (ornityl carbamyl transferase), Ar (arginase), SDH (sorbite dehydrogenase)

50
Q

OCT (ornityl carbamyl transferase), Ar (arginase), SDH (sorbite dehydrogenase) are what?

A

Parenchymal enzymes, their activity increase when there is liver cell damage

51
Q

SDH, liver specific in what species?

A

Swine, cattle, horse

52
Q

OCT liver specific in what species?

A

Dogs

53
Q

AR liver specific in what species?

A

Dogs and horses

54
Q

What to measure? Dog:

A

ALT
(AST, GLDH)
ALKP
GGT

55
Q

What to measure? Cat:

A

ALT
(AST, GLDH) not routinely measured
GGT
(ALKP, in acute processes)

56
Q

What to measure? Ruminants:

A

AST
GLDH
(GGT) not routinely measured

57
Q

What to measure? Horse:

A

AST
GGT
(Ar) not routinely measured

58
Q

What to measure? Swine:

A 
AST
GGT
ALKP
OCT
SDH
59
Q

Examination of change in lipid metabolism due to impaired liver function; cause of decreased total cholesterol conc.

A
  • Decreased esterification ability (decreased cholesterol-ester formation)
  • Decreased apolipoprotein synthesis (decreased transport of cholesterol due to decreased HDL and LDL synth.)
60
Q

Examination of change in lipid metabolism due to impaired liver function; increased FFA conc. in case of increased energy demand (lipaemia), cause?

A

Decreased FFA utilization especially in case of increased energy demand

61
Q

Examination of change in lipid metabolism due to impaired liver function; cause of lipid accumulation in liver?

A
  • Decreased ability to perform a beta oxidation (decreased lipid breakdown)
  • Decreased synth. of lipid-transporting apolipoprotein molecules (decreased HDL, LDL and VLDL synth.)
62
Q

Other diagnostic approaches?

A

Liver biopsy or aspiration cytology

Lipid content evaluation from the liver biopsy sample

63
Q

Liver biopsy or aspiration cytology;

A
  • Routine cytology or histology
  • Laboratory evaluation of lipid, protein, glycogen etc. content of the liver
  • Histology approach considered best alternative
64
Q

Lipid content evaluation from the liver biopsy sample; + normal gravity of liver + lipid content normal range

A
  • 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
Q

Physiological increase of lipid content in dairy cows, normal range; Gravity

A

1,04 g/ml

66
Q

Physiological increase of lipid content in dairy cows, normal range; Lipid content

A

100-120 g/kg

67
Q

Physiological increase of lipid content in dairy cows, normal range; pathological increase of lipid content, gravity

A

1,01 g/ml

68
Q

Physiological increase of lipid content in dairy cows, normal range; Lipid content

A

300-400 g/kg

69
Q

Normal value ammonia conc. Dog and Cat

A

Dog: 26,4-70,5 umol/L
Cat: 17,6-58,7 umol/L

Pathophysio (12 decks)

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