Liver and Pancreas Flashcards

1
Q

Liver receives blood from? Known as ____ vessels.

A

AFFERENT

  1. Portal vein - nutrient rich, oxygen poor—70-80%
  2. Hepatic artery–oxygen rich–20-30%
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2
Q

Glisson’s capsule

A

FIBROconnective (type III collagen) tissue capsule that divides liver in lobes and lobules
SIMPLE SQUAMOUS

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3
Q

Functions of the liver

A
  1. gluconeogenesis
  2. detoxification (via conjugation and oxidation and stuff)
  3. Storage- fat, glycogen, fat soluble vitamins (ADEK)
  4. Bile production in sER (EXOCRINE)
  5. Plasma protein synthesis (ENDOCRINE)
  6. transfer of IgA into bile canaliculi
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4
Q

What are some serum proteins the liver makes?

A

Endocrine= fibrinogen, prothrombin, albumin, c- reactive protein. Also makes urea for excretion.

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5
Q

Blood exits liver via (AKA ___ vessels)

A

EFFERENT

central vein

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6
Q

Main cell of the liver

  1. Shape
  2. stain
  3. organelles
A

Hepatocytes=parenchymal cells

  1. Polyhedral epithelial cells
  2. eosinophilic cytoplasm (rich in mitochondria)
  3. Large round central nuclei (sometimes binucelate), with abundant rER, sER, lysosomes, peroxisomes, and funky microvilli on side with space of disse AND
  4. glycogen deposits and lipid droplets
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7
Q

parenchymal cell-definition??

A

Looked this up, it means its a functional cell rather than a structural cell. FYI.
Stroma= Structural, CT

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8
Q

hepatocyte DNA-significance?

A

can be diploid or polyploid. Liver cells will divide if part of liver is removed.

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9
Q

Hepatocyte arrangement (classic)

A

HEXAGONAL arrangement of hepatocyte plates around central vein

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10
Q

Portal canal= ____ = ___

Contains?? ?

A

Portal canal= portal triad= portal area

Branches of portal vein, hepatic artery, bile duct. Sometime lymph

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11
Q

Location of portal canal

A

found at periphery of lobules.

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12
Q

Flow of blood in portal areas?

A

INTO liver sinusoids –> central vein

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13
Q

Liver sinusoids

  1. location
  2. features
  3. Cells
  4. Blood found here?
A
  1. spaces between hepatocyte plates
  2. Lined with fenestrated endothelial cells and NO BASAL LAMINA
  3. KUPFFER CELLS
  4. Mixed venous and arterial
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14
Q

Another “space” between liver cells. (between the sinusoids and hepatocyte)

  1. Contains
  2. Function (x2)
A

Space of Disse
1. filled with plasma, Ito cells, and reticular fibers
2.
A. microvilli (*irregular) of hepatocytes “bathed” in plasma = exchange of material between blood and hepatocytes.
B. Vitamin A storage in Ito cells

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15
Q

Kupffer cells (aka?)

  1. location, shape
  2. function (X3)
  3. lineage
A

AKA stellate macrophages
1. sinusoids lining, crescent shaped
2.
A. phagocytose old RBC which frees Fe and Heme for reuse or storage in ferritin.
B. Antigen presenting cells that get rid of debris
C. Can release cytokines that induce collagen production in stellate cells.
3. monocytic lineage

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16
Q

Stellate macrophages vs hepatic stellate cells

A

DONT MIX THESE UP
stellate macrophages are Kupffer cells found in sinusoids responsible for macrophaging.

Hepatic stellate cells are in the space of Disse= perisinusoidal space and are responsible or vit A storage and making ECM

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17
Q

What helps “free” iron and heme? what happens when they’re freed?

A

Kupffer cells free them from old RBC. they bind ferritin or are reused.

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18
Q

Hepatic stellate cells (AKA)

  1. Location
  2. Function
  3. Characteristics
A

AKA cells of Ito

  1. Space of Disse/perisinusiodal space/subendothelial space
  2. Store Vit A (and other fat-sol vits); make ECM and collagen in response to cytokines (from kupffer and hepatocytes)
  3. small lipid droplets in them (have the vit A)
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19
Q

Models of liver organization

A
  1. Classic lobule
  2. Portal lobule
  3. Hepatic acinus
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20
Q

Classic lobule

  1. Arrangement
  2. Flow of material
A
  1. hepatocytes organized hexagonally around central vein.

2. into central vein

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21
Q

Portal lobule

A

Based on 3 central veins and one portal area. triangle is flow of bile into bile duct

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22
Q

Hepatic acinus

A

AKA Acinus of Rappaport
2 central veins= oval/diamond area with metabolic gradient. Zone 3= drainage zone
Zone 1= periportal zone

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23
Q

Apical side of hepatocyte vs basolateral side.

A
Apical= bile canaliculi
Basolateral= process nutrients and stuff from blood
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24
Q

Within a lobule, how does the function of a central hepatocyte differ from the peripheral hepatocyte?

A

Peripheral hepatocytes are near portal area and get more O2 allowing them to make proteins, cholesterol and gluconeogenesis. Central hepatocytes have less nutrients and O2 and work more on detox and glycogen metabolism.

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25
Q

Hepatocytes in Zones 1-3?

A

Zone 1= oxidative functions
Zone 2= intermediate
Zone 3= detox, can become hypoxic

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26
Q

What model is based on

  1. 1 central v
  2. 2 central v.
  3. 3 central v.
A
  1. Classical- flow of blood to central vein = ENDOCRINE F(X) of liver.
  2. acinus of rappaport (metabolic activity)
  3. portal lobule (flow of bile)= EXOCRINE
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27
Q

Flow of bile and blood?

A

opposite directions.

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28
Q

Bile is a ___ secretion

A

EXOCRINE

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29
Q

Bile canaliculi

A

Where bile is secreted. INTERcelllar space between apical surface of hepatocytes.

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30
Q

Flow of bile (start at hepatocyte)

A

Apical hepatocyte–> bile canaliculi –> canals of hering= bile ductule –>bile ducts –>hepatic (rt/left) duct –> common hepatic joins cystic duct –>common bile duct

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31
Q

Canal of hering

A

bile ductULE found at periphery of lobules

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32
Q

Bile contains?

A

cholesterol, phospholipids, bile salts, conjugated bilirubin and electrolytes
(so all these are excreted with bile)
Also IgA and drugs and heavy metals?

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33
Q

Bile function

A

Absorption of fat and fat soluble vitamins.

34
Q

Circulation of bile acid?

A

90%
reabsorbed in ILEUM –> portal system–> sinusoid–> enter hepatocyte via basolateral side and exits via apical side –>bile canaliculi

35
Q

What help transport bile components into the canaliculs?

A
  1. MDR1- multidrug resistant ATPase=cholesterol
  2. MDR2=phospholipids
  3. MOAT=multispecific organ anion transport = glutathione conjugates
  4. BAT= biliary acid transport= bile salt
    * *also has HCO3/Cl- “exchanger” but both arrows from canaliculus into hepatocyte…?
36
Q
Old RBC (start at spleen) ---> bile, eventually
5 steps
A

Splenic macrophage
1. RBC–>bilverdin–>bilirubin released in blood
Blood
2. bilirubin binds albumin and travels to hepatocyte
3. bilirubin enters hepatocyte, binds ligandin and enters sER
4. free bilirubin exits sER and is conjugated in cytosol
5. bilirubin + glucaronic acid= conjugated bilirubin= direct bilirubin –>secreted into bile.

37
Q

Defect in MDR2?

A

Focal hepatic necrosis and bile ductule proliferation

38
Q

Bilirubin
Bilirunin: albumin
Conjugated bilirubin

hydrophilic or phobic?

A

Bilirubin= hydrophobic
Bilirubin: albumin= hydrophilic
Conjugated bilirubin= hydrophilic

39
Q

IgA

A

mucosal antibody. Made by plasma cells in intestinal mucosa and enter circulatory system–>liver.
liver combines igA with secretory component and releases into bile.

40
Q

Cirrhosis of liver causes collagen formation–how?

A

Kupffer cells release cytokines (TGF-Beta) which cause Cells of Ito=hepatic stellate cells to produce collagen (type I). They become myofibroblasts, i guess.

41
Q

Hep A , B , C

A

Cause inflammation of the liver
A= infectious fecal or oral
B=serum (blood and products)
C=hepatocellular carcinoma

B &C transfusion related

42
Q

Cirrhosis of liver

A

Degeneration and fibrosis, damaged hepatocytes. Caused by poisoning, EtOH abuse + fatty liver (from steatosis)

43
Q

Jaundice

A

Excess bilirubin in blood due to obstructed bile passages, RBC destruction or inability to conjugate bilirubin.

44
Q

Steatohepatitis

A

accumulation of fat in hepatocytes that causes inflammation of liver

45
Q

cholangiocytes–not in our notes but kinda impt

A

line canals of hering (where bile canaliculi drain).

Cuboidal or columnar cells with distinct CT sheath

46
Q

CHF

A

causes increased central venous pressure = liver is enlarged (engorged with blood)

47
Q

Portal hypertension

A

obstructed blood flow associated with cirrhosis. leads to ascites (fluid accumulation in peritoneal cavity).

48
Q

Consequence of pancreatic carcinoma?

A

Obstruction of bile outflow from liver

49
Q

Free bilirubin is…

A

TOXIC TO BRAIN.

50
Q

Hyperbilirubinemia can be caused by:

A
  1. hemolytic diseases= excess destruction of RBC (ex: erythroblastosis fetalis)
  2. Liver dysfunction
  3. Bile passage blockage
51
Q

Cholestasis

A

Slow/stopped bile outflow.

Caused by TNF-alpha release from kupffer cells.

52
Q

Alcohol metabolism

A

2 Routes

  1. ADH (alcohol dehydrogenase)= forms acetaladehyde and H+
  2. MFO (mixed function oxidase system in sER using cytochrome p450)= formation of acetalaldehyde and ROS
53
Q

Acetalaldehyde?

A

Excess causes damage to mitochondria and microtubules

54
Q

Gallbladder

  1. Function
  2. Regulation
A
  1. stores bile and releases it into duodenum

2. cholecystokinin induces releases of bile from gallbladder

55
Q

Gallbladder

  1. Epithelium
  2. Lamina propria
  3. Submucosa
  4. Muscularis externa
  5. Serosa/adventitia?
A
  1. Simple columnar epithelium with microvilli on APICAL surface with DIVERTICULA
  2. loose connective tissue with Rokitansky-Aschoff sinuses (epithelial lined cysts caused by diverticulations in epithelium)
  3. no real submucosa
  4. thin fascicles of SM fibers (oblique layer)
  5. adventitia where attached to liver, but serosa on the rest
56
Q

Gallbladder KEY FEATURE

A

Rokitansky-Aschoff sinuses

epithelium has diverticula that form epithelial lined cysts in lamina propria

57
Q

Gallstones- types

A
  1. biliary calculi- cholesterol crystals

2. calcium bilirubinate= stones made from bile salt caclium

58
Q

Pancreas-what kind of organ?

A

Exocrine and endocrine

59
Q

Pancreas divisions?

A

divided into lobules by septa from CT capsule

60
Q

Endocrine pancreas cells found in?

A

Islets of langerhans

61
Q

Cell types of endocrine pancreas?

Function and percentage of total cells

A
  1. Alpha cells= make glucagon, 15-20%
  2. beta cells= make insulin 60-70%
  3. delta cells= make somatostatin= inhibition of hormone release by neighbor cells. 5%
  4. Epsilon- ghrelin- appetite stimulator. <1%
  5. PP cells or F cells= pancreatic polypeptide–inhibit exocrine secretions. 10%
62
Q

inhibition of endocrine secretions? (of pancreas)

A

D-cells= somatostatin inhibits hormone release.

63
Q

Inhibition of exocrine secretions of pancrease.

A

PP cells/F cells via pancreatic polypeptide

64
Q

Cholecystokinin

  1. released from?
  2. function?
A
  1. released from enteroendocrine cells.
  2. causes bile secretion from gallbladder and pancreatic secretion of: amylase, lipase, ribonuclease, and deoxyribonuclease
65
Q

Exocrine pancreas releases?

A

LOTS OF STUFF= ACINAR CELLS

  • Amylase, lipase, ribonuclease and deoxyribonuclease
  • trypsin, chymotrypsin, carboxypeptidase and elastase in proenzyme form (zymogens)
  • bicarbonate
66
Q

Secretin

  1. released rom
  2. function
A
  1. released from enteroendocrine cells
  2. induces release of bicarbonate from intercalated duct cells= CENTROACINAR CELLS
    also HCO3 release from biliary tract
67
Q

Where are endocrine cells found in the pancreas?

A

Found in collections called “islets of langerhans” surrounded by reticular fiber network. Islets located amongst acinar cells of exocrine pancreas.

68
Q
  1. Acinus drained by?
  2. What cells line it? Do they do anything? If so, what activates/deactivates them?
  3. What does acinus secrete, what activates it to secrete that?
A
  1. Intercalated duct
  2. simple squamous epithelium = centroacinar cells= secrete HCO3 (in response to SECRETIN)
  3. CCK stimulates acinar cell secretion=pancreatic digestive enzymes
69
Q

Intercalated duct drains to?- epithelium?

A

Intralobular duct lined by CUBOIDAL epithelium

70
Q

Intra lobular duct drains into?

A

Interlobular ducts-lots of CT

71
Q

Interlobular ducts drain to?

A

main pancreatic duct

72
Q

Summary- drainage of exocrine pancrease

A

Acinar cells release zymogens into intercolated ducts in response to CKK. Centroacinar cells (simple squamous) release HCO3 to keep zymogens inactive (in response to secretin). Exocrine stuff moves from intercalated ducts to intralobular ducts (cuboidal epithelium) to interlobular ducts (lots of CT) to pancreatic duct

73
Q

Type I Diabetes

  1. symptoms
  2. onset
  3. Insulin independent/dep?
A
  1. polydipsia, polyphagia, polyuria
  2. before 20 yrs
  3. Insulin dependent
74
Q

Type II Diabetes

  1. patient stats
  2. insulin indep/dep?
  3. Contributions to development?
A
  1. fat, older
  2. NON insulin dep-insulin levels can be normal, impaired release, receptors, post-receptor signaling.
  3. muscle insulin resistance, hepatic insulin resistance causing too much insulin production
75
Q

Causes of HIS

-what can it cause?

A

HIS=hepatic insulin resistance
faulty insulin receptor substrate (IRS) that connects insulin receptor to downstream kinase cascades like PI3K or MAPK. Contributes to Type II diabetes.

76
Q

Pancreatitis

Acute necrotizing pancreatitis

A

inflammation usually from gallstones.

Acute necro= from infection, gall stones, trauma– activation of proezymes causes digestion of pancrease.

77
Q

What causes kupffer cells to release cytokines? What are they and effects?

A

chronic liver disease (viral, bacterial, alcohol) causes release of

  1. TNF-alpha= cholestasis
  2. TGV-beta= Cells of Ito to make more collagen
  3. IL6= hepatocytes release acute phase proteins
78
Q

Hepatocyte during chronic liver disease

A
  1. IL6 from Kupffer cell

2. TGF-beta to stellate cell= increased type 1 collagen

79
Q

Alcohol metabolism in liver

  1. Mitochondria
  2. sER
A
  1. Mitochondria= Alcohol dehydrogenase–> acetalaldehyde and H+
  2. sER= MFO system –> acetalaldehyde + ROS
80
Q

Where are reticular fibers found (liver, pancreas, gallbladder?)

A
  1. space of disse (liver)

2. Islet of langerhans (pancreas)