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603 Physiology > Hepatic 1 > Flashcards

Hepatic 1 Flashcards

1
Q

How many functions does the liver have?

A

more than 500

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2
Q

Top 5 [Categorical] Functions of the Liver

A
  1. Transportation
  2. Synthesis
  3. Detox
  4. Energy Storage
  5. Waste Management
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3
Q

What % of body weight is the liver typically?

A

2-3%

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4
Q

microhepatica

A

liver is smaller than it should be

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5
Q

portosystemic shunt

A

blood isn’t getting filtered through the liver, it is going directly to thecaudal vena cava, and causes many other problems, including seizures

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6
Q

How can cows get sunburn due to liver failure?

A

photoreactive compounds from grass can’t be removed by the liver so they go into circulation and near the skin they can be activated so oxygen reactive species can cause damage to cells

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7
Q

Theiler’s disease

A

bioloical agent that causes hepatocytes to die and the liver becomes very soft with less function

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8
Q

hepatic amyloidosis

A

accumulation of amyloid in the liver, which gets an elasic/rubbery/waxy texture

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9
Q

Accumulation of amyloid in neurological system?

A

Alzheimer’s disease

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10
Q

What two vessels supply the liver?

A
  1. Hepatic artery
  2. Portal vein
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11
Q

How much of the total liver circulation does the portal vein supply?

A

70-75%

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12
Q

Hepatic parenchyma organization

A

polygonal lobules of hepatocytes surrounded by portal triads with a centrally located vein

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13
Q

sinusoids

A

microvasculature with fenestrated endothelial cells [in the middle of each hepatic lobule)

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14
Q

stellate (Ito) cells

A

store Vitamin A (lots of lipids); responds to damage by producing collagen and causing fibrogensis

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15
Q

Space of disse

A

space below the hepatocytes that contains stellate cells

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16
Q

Kupffer cells

A

macrophages within hepatic sinusoids (80-90% of the mononuclear phagocyte system)

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17
Q

What is the vein in the center of a hepatic lobule?

A

central vein

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18
Q

Portal Triad (3)

A
  1. Bile duct
  2. Hepatic artery
  3. Portal vein
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19
Q

parenchyma

A

functional tissue of an organ

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20
Q

stroma

A

part of tissue with a structural/connnective role (ex: CT, vessels, ducts, etc)

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21
Q

3 Zones of the Parenchyma Liver (from outside to inside)

A

Zone 1 = Periportal
Zone 2 = Mid-zonal
Zone 3 = Centrilobular

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22
Q

How can you define a hepatic lobule histologically?

A

Find your large central vein and the portal trieads surrounding it, and then guesstimate.
(much easierto see in pig liver)

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23
Q

Zone with highest oxygen content?

A

Zone 1

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24
Q

Zone with highest cytochrome P450 (CYP450)?

A

Zone 3

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25
Q

CYP450

A

enzyme bound to membrane within a cell and contains a heme pigment that absorbs light at 450nm when exposed to carbon monoxide

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26
Q

Biliary drainage

A

from middle of lobule to outside, collected by canniculi b/n hepatocytes and carried to interlobular bile ducts before going to the hepatic ducts to gallbladder/main bile duct

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27
Q

Extramedullary Hematopoiesis (EMH)

A

site of red and white blood cell production that occurs outside of the bone marrow

28
Q

Major sites of EMH

A

liver and spleen

29
Q

Erythoid cells

A

precursor to blood cells

30
Q

Does CYP450 need a lot of oxygen?

31
Q

How to differentiate erythroids and granulocytes from lymphosarcoma histologically

A

granulocytes will accumulate around vasculature, lymphosarcoma is everywhere

32
Q

4 Main Steps of Detoxification

A
  1. Hepatocytes pick up with compound from the blood (sinusoids) and transport it across the basolateral membrane
  2. Transport within the hepatocyte
  3. Chemical modification/degradation in intracellullar compartment
  4. Excretion of molecule/products as bile avcross the apical membrane into canniliculi
33
Q

What substances can be taken up by hepatocytes through the basolateral surface?

A

bile acids/salts, organic anions/cations, neutral organic compounds, bilirubin

34
Q

3 Main Mechanisms of Endocytosis

A
  1. Receptor-Mediated
  2. Adsorptive
  3. Fluid-phase
35
Q

Is adsorptive endocytosis selective?

A

no, it is non-selective

36
Q

Pinocytosis

A

another name for fluid phase endocytosis; uptake of fluid and asssociated [dissolved] solutes

37
Q

Receptor-Mediated Endocytosis

A

MOST IMPORTANT
compounds bind to receptor an triggers a clathrin coated pit to form which detaches from basolateral membrane and forms a vesicle to be transported to other organelles within the cell

38
Q

2 Pathways for Transport within the Hepatocyte

A
  1. Protein-bound (ex: albumin)
  2. Vesicle pathway
39
Q

Fastest transport within the cell?

A

protein bound

40
Q

2 Methods of Degradation within the Hepatocyte

A
  1. Lysosome degradation
  2. Biotransformation
41
Q

Which degradation method is unique to hepatocytes?

A

biotransformation

42
Q

Lysosome degradation

A

compounds have carrier proteins for lysosomal uptake, acid hydrolases break down larger compounds; not unique to hepatocytes

43
Q

Biotransformation

A

Converts non-polar molecules into polar molecules so they can be dissolved in water to be excreted as bile or urine

44
Q

2 Phases of Biotransformation

A
  1. Oxidation/Reduction Rxns
  2. Conjugation of Phase 1 products to another polar group to inc. water solubility
45
Q

Hydroxylation is catalyzed by what?

A

cytochrome P450 enzymes

46
Q

Redox Rxns

A

intoduce a functional group for a small increase in hydrophilicity

47
Q

Can compounds skip phase 2 of biotransformation?

A

technically yes but most will need it anyway

48
Q

CYP450 accounts for what % of drug metabolism in the liver?

49
Q

Drugs that INDUCE CYP450

A

phenobarbital, St. John’s Wort

rapid metabolism and therefore more rapid clearance

50
Q

Drugs that INHIBIT CYP450

A

metronidazole, terbinafine, grapefruit juice

slower metabolism, amplifies effects of other drugs d/t decreased clearance

51
Q

If an animal experiences drug toxicity/overdose, in what zone of the lobule will you see the most damage?

A

centrilobular (Zone 3)

52
Q

In which phase of biotransformation is CYP450 critical?

53
Q

3 Possible Reactions in Phase 2 of Biotransformation

A
  1. Glucuronate conjugation
  2. Sulfate conjugation
  3. Glutathione conjugation
54
Q

Most important rxn in Phse 2 of biotransformation?

A

Glucuronate conjugation

55
Q

Enzyme of Glucuronate Conjugation

A

UGTs (resides in smooth ER of hepatocytes)

(uridine diphosphte gluucuronosyltransferase)

56
Q

Enzyme of Sulfate Conjugation

A

Sulfotransferases (in the cytosol)

57
Q

Do sulfate and glucuronate conjugation compete or cooperate?

A

cooperate (different locations within the cell)

58
Q

Enzyme of Glutathione Conjugation

A

Glutathioine-S-tranferases (in the cytosol)

59
Q

The three AAs that make up glutathione

A

glutamate
cysteine
glycine

60
Q

Which AA can be removed from glutathione sometimes?

A

Glutamate (by GGT in the bile duct epithelial cells)

61
Q

Enzymatic marker for bile duct dystfunction?

A

GGT (gamma-glutamyl transpeptidase)

62
Q

Why is maintaining glutathione levels important?

A

glutathione prevents damage/cell death caused by reactive oxidative species

63
Q

Toxic Dose of Acetaminophen in Cats

A

50-100mg/kg

64
Q

Clinical Signs of Acetaminophen Toxicity? What is their main cause?

A

increased RR, pale MMs, hypothermia, tachycardia

DECREASED OXYGEN

65
Q

NAPQI

A

metabolite of acetaminophen

66
Q

Why do cats have a harder time breaking down acetaminophen than other species?

A

they are deficient in glucuronyl transferases (less than 3% compared to 50-60% in others), so NAPQI persists as a reactive species

67
Q

Why does acetaminophen cause tissue hypoxia in cats?

A

NAPQI persists (simply not enough glutathione to keep up), causes cell death; iron is also oxidized resulting in methemoglobinemia (MetHb), which needs more oxygen so less is released to tissues

603 Physiology (22 decks)

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