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603 Physiology > Hepatic 1 > Flashcards

Hepatic 1 Flashcards

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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
CYP450
enzyme bound to membrane within a cell and contains a heme pigment that absorbs light at 450nm when exposed to carbon monoxide
26
Biliary drainage
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
27
Extramedullary Hematopoiesis (EMH)
site of red and white blood cell production that occurs outside of the bone marrow
28
Major sites of EMH
liver and spleen
29
Erythoid cells
precursor to blood cells
30
Does CYP450 need a lot of oxygen?
no
31
How to differentiate erythroids and granulocytes from lymphosarcoma histologically
granulocytes will accumulate around vasculature, lymphosarcoma is everywhere
32
4 Main Steps of Detoxification
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
What substances can be taken up by hepatocytes through the basolateral surface?
bile acids/salts, organic anions/cations, neutral organic compounds, bilirubin
34
3 Main Mechanisms of Endocytosis
1. Receptor-Mediated 2. Adsorptive 3. Fluid-phase
35
Is adsorptive endocytosis selective?
no, it is non-selective
36
Pinocytosis
another name for fluid phase endocytosis; uptake of fluid and asssociated [dissolved] solutes
37
Receptor-Mediated Endocytosis
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
2 Pathways for Transport within the Hepatocyte
1. Protein-bound (ex: albumin) 2. Vesicle pathway
39
Fastest transport within the cell?
protein bound
40
2 Methods of Degradation within the Hepatocyte
1. Lysosome degradation 2. Biotransformation
41
Which degradation method is unique to hepatocytes?
biotransformation
42
Lysosome degradation
compounds have carrier proteins for lysosomal uptake, acid hydrolases break down larger compounds; not unique to hepatocytes
43
Biotransformation
Converts non-polar molecules into polar molecules so they can be dissolved in water to be excreted as bile or urine
44
2 Phases of Biotransformation
1. Oxidation/Reduction Rxns 2. Conjugation of Phase 1 products to another polar group to inc. water solubility
45
Hydroxylation is catalyzed by what?
cytochrome P450 enzymes
46
Redox Rxns
intoduce a functional group for a small increase in hydrophilicity
47
Can compounds skip phase 2 of biotransformation?
technically yes but most will need it anyway
48
CYP450 accounts for what % of drug metabolism in the liver?
75%
49
Drugs that INDUCE CYP450
phenobarbital, St. John's Wort rapid metabolism and therefore more rapid clearance
50
Drugs that INHIBIT CYP450
metronidazole, terbinafine, grapefruit juice slower metabolism, amplifies effects of other drugs d/t decreased clearance
51
If an animal experiences drug toxicity/overdose, in what zone of the lobule will you see the most damage?
centrilobular (Zone 3)
52
In which phase of biotransformation is CYP450 critical?
Phase 1
53
3 Possible Reactions in Phase 2 of Biotransformation
1. Glucuronate conjugation 2. Sulfate conjugation 3. Glutathione conjugation
54
Most important rxn in Phse 2 of biotransformation?
Glucuronate conjugation
55
Enzyme of Glucuronate Conjugation
UGTs (resides in smooth ER of hepatocytes) (uridine diphosphte gluucuronosyltransferase)
56
Enzyme of Sulfate Conjugation
Sulfotransferases (in the cytosol)
57
Do sulfate and glucuronate conjugation compete or cooperate?
cooperate (different locations within the cell)
58
Enzyme of Glutathione Conjugation
Glutathioine-S-tranferases (in the cytosol)
59
The three AAs that make up glutathione
glutamate cysteine glycine
60
Which AA can be removed from glutathione sometimes?
Glutamate (by GGT in the bile duct epithelial cells)
61
Enzymatic marker for bile duct dystfunction?
GGT (gamma-glutamyl transpeptidase)
62
Why is maintaining glutathione levels important?
glutathione prevents damage/cell death caused by reactive oxidative species
63
Toxic Dose of Acetaminophen in Cats
50-100mg/kg
64
Clinical Signs of Acetaminophen Toxicity? What is their main cause?
increased RR, pale MMs, hypothermia, tachycardia DECREASED OXYGEN
65
NAPQI
metabolite of acetaminophen
66
Why do cats have a harder time breaking down acetaminophen than other species?
they are deficient in glucuronyl transferases (less than 3% compared to 50-60% in others), so NAPQI persists as a reactive species
67
Why does acetaminophen cause tissue hypoxia in cats?
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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