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BMS150 Post-MT2 > Physiology and Pathology: Liver & Gallbladder > Flashcards

Physiology and Pathology: Liver & Gallbladder Flashcards

1
Q

Livers special role in the circulatory system - receives portal blood that drains into…? (5)

A
  • Stomach
  • Small intestine
  • Large intestine
  • Pancreas
  • Spleen
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2
Q

What is the livers important role in immunology?

A

Kupffer cells (in liver) = up to 80% of mononuclear phagocyte system

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3
Q

4 lobes of the liver?

A
  • Right lobe
  • Left lobe
  • Quadrate lobe (inferior)
  • Caudate lobe (posterior)
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4
Q

Which lobe of the liver is never palpable?

A

Caudate lobe

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5
Q

Important ligaments of the liver? (4)

A
  • Coronary lig.
  • Falciform lig.
  • Round lig.
  • Ligamentum venosum
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6
Q

Ligaments that anchors the liver to the diaphragm?

A

Coronary ligaments

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7
Q

Ligament that separates right and left lobes of liver?

A

Falciform ligament

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8
Q

Ligament found on free border of falciform ligament separates quadrate and left lobe

A

Round ligament

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9
Q

Other name for round ligament?

A

Ligamentum teres

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10
Q

What is the embryological significance of the round ligament (ligamentum teres)?

A

Remnant if the left umbilical vein - connects liver to umbilicus

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11
Q

Ligament that separates the caudate and left lobe

A

Ligamentum venosum

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12
Q

What is the embryological significance of the ligamentum venosum?

A

Fibrous remnants of ductus venosus from fetal circulation

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13
Q

What separates quadrate lobe and right lobe?

A

Gallbladder

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14
Q

Liver receives oxygenated blood from the ________

A

Hepatic artery

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15
Q

Liver receives deoxygenated, nutrient rich blood from the ________

A

Hepatic portal vein

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16
Q

Where both arteries in the liver enter?

A

Porta hepatis

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17
Q

What is the Porta hepatis an opening for? (3)

A
  • Hepatic artery
  • Portal vein
  • Common hepatic duct
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18
Q

Three main histological components of liver?

A
  • Hepatocytes
  • Bile canaliculi/cholangiocytes
  • Hepatic sinusoids
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19
Q

Major functional cell of the liver?

A

Hepatocyte

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20
Q

Hepatocytes are specialized _______ cells arranged into _______

A

epithelial; hepatic laminae

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21
Q

Hepatic laminae structure?

A

Highly branched plates of hepatocytes bordered by hepatic sinusoids

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22
Q

Grooves in the cell membrane of neighboring hepatocytes provide space for…?

A

bile canaliculi

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23
Q

What are hepatocytes arranged into?

A

Lobules

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24
Q

Hepatic lobules surround a ______ and are cornered by ______

A

central vein; portal triad

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25
Q

What does the central vein drain? Where does it empty?

A
  • Drains: hepatic sinusoids
  • Empties into: Hepatic vein
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26
Q

What is the Portal triad? What are the arteriole and venule branches?

A
  • It’s a bile duct
  • Art: branch of hepatic art
  • Ven: branch of portal vein
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27
Q

Small ducts found between hepatic laminae that collect bile?

A

Bile canaliculi

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28
Q

Lining of bile ductules and ducts?

A

Cholangiocytes

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29
Q

Capillary system specific to the liver?

A

Hepatic sinusoids

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30
Q

Hepatic sinusoids are _______ discontinuous endothelium

A

Fenestrated

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31
Q

What are hepatocytes separated from sinusoids by?

A

Space of Disse

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32
Q

What mixes in the hepatic sinusoids?

A

Blood from the portal vein and hepatic artery

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33
Q

what are normally found in a quiescent state in the space of Disse?

A

Hepatic stellate cell/Ito cell

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34
Q

Major cell type in liver fibrosis?

A

Hepatic stellate cell/Ito cell

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35
Q

When do hepatic stellate cells become active?

A

When there is damage

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36
Q

What do hepatic stellate cells do in response to damage?

A

Secrete collagen and extracellular matrix = scar tissue formation

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37
Q

Hepatic stellate cells have several long protrusions that ________

A

Wrap around sinusoids

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38
Q

What do hepatic stellate cells store?

A

Lipid droplets in cell body containing Vitamin A retinol esters

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39
Q

Resident macrophages of the liver?

A

Kupffers cells

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40
Q

Where are Kupffer cells derived from?

A

Circulating monocytes

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41
Q

Functions of Kupffer cells? (5)

A

Phagocytose:
- Old RBCs
- Hemoglobin
- Particulate matter
- Cellular debris
- Microorganisms

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42
Q

Hepatocytes, bile duct system and hepatic sinusoids can be organized into functional units called ______

A

Hepatic acinus

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43
Q

What is hepatic acinus?

A

Ovular mass that includes portions of 2 neighbouring hepatic lobules

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44
Q

Two axes of hepatic acinus?

A
  • Short: branches of portal triad
  • Long: connects 2 central veins to short axis
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45
Q

Hepatocytes are arranges into 3 zones around the short axis, what are they?

A
  • Zone 1 - most O2
  • Zone 2
  • Zone 3 - least O2
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46
Q

T/F: Hepatocyte function differs based on zone within hepatic acinus

A

True

47
Q

Hepatocytes in zone 1 specialize in…?

A

Oxidative metabolism

48
Q

Hepatocytes in zone 3 specialize in…?

A

Biotransformation of drugs

49
Q

Liver functions? (4)

A
  • Biotransformation and degradation
  • Bilirubin conjugation
  • Storage/synth of nutrients
  • Bile production
50
Q

Why does the liver have to process lipophilic chemicals into polar, water soluble metabolites?

A

Need to be water soluble to transport them through blood or excrete them into bile

51
Q

4 major steps of biotransformation and degradation

A
  1. Imports compound
  2. Transport w/in cell
  3. Chemically modify/degrade
  4. Excretion into bile
52
Q

What kind of pumps at the basolateral membrane provides energy for transporting a wide variety of solutes into hepatocyte?

A
  • Na-K pump
  • Organic anion-transporting polypeptides (OATPs)
  • Organic cation transporter (OTC)
53
Q

What are OATPs responsible for?

A

Uptake of a variety of endogenous & exogenous amphipathic compounds (bile acids, biliribun, PGs)

54
Q

What are OTCs responsible for?

A

Uptake of a variety of lipophilic organic cations (acyclovir, epi, norepi, histamine)

55
Q

Two phases of modification stage?

A
  • Phase I - Redox by CYP450
  • Phase II - conjugation
56
Q

Oxidation-reduction reactions that can happen in phase I?

A

Hydroxylation, dealkylation, dehalogenation

57
Q

What happens in the conjugation phase? Why?

A

Addition of highly hydrophilic compound = water soluble for transport

58
Q

What compounds are typically involved in conjugation?

A

Glutathione, sulfate, glucuronate

59
Q

What adds glucuronic acid?

A

Uridine diphosphate gluconosyntransferase (UGT)

60
Q

Overall, what is the sequence of reactions occurring in the modification stage of biotransformation?

A

RH => ROH => RO-conjugate

61
Q

What is the conjugated compound transported out of the hepatocyte into?

A
  • Blood via sinusoidal memb
  • Bile across canalicular memb
62
Q

What does transport of the conjugated compound out of the hepatocyte require?

A

ATP-binding cassette (ABC)

63
Q

Conjugated bilirubin will be carried to the liver by what?

A

Albumin

64
Q

In the liver, bilirubin will be ______, and what will be added?

A

Conjugated; glucuronic acid

65
Q

Bilirubin glucuronide will be excreted into what?

A

Bile

66
Q

What do bacteria in the terminal ileum and colon convert some of the conjugated bilirubin into?

A

Back into bilirubin

67
Q

What is the bilirubin in the colon/terminal ileum then converted to?

A

urobilinogen

68
Q

What are two things that can happen to urobilinogen?

A
  • convert to stercobilin (pigment of feces)
  • reabsorbed and filtered by kidneys (gives urine yellow colour)
69
Q

What are nutrients brought to the liver by?

A

Hepatic portal vein

70
Q

Depending on metabolic requirements, what can happen to the substrates brought to the liver? (3)

A
  • Stored by hepatocytes
  • Released unbound into circulation
  • Bound to carriers and released into circulation
71
Q

Essential substances the liver can synthesize?

A

Albumin, coagulation factors, plasmaproteins

72
Q

Two functions of bile production by the liver?

A
  1. Elimination of exogenous and endogenous waste
  2. Promotes digestion and absorption of lipids from intestines
73
Q

What is bile initially synthesized from? What does this yeild and what do they become?

A

Cholesterol - primary bile acids
- will be conjugated and become primary bile salts

74
Q

In the terminal ileum of the colon, be ______ by bacteria and reabsorbed. These become what?

A

Dehydroxylated; secondary bile salts

75
Q

Other components of Bile?

A
  • Phospholipids
  • IgA
  • Excretory waste products
76
Q

Excretory waste products in bile? (5)

A
  • Cholesterol
  • Bile pigment (bilirubin)
  • Lipophilic drugs and metabolites
  • Oxidized GSH
  • Trace minerals
77
Q

Bile flow pathway?

A

Hepatocyte => bile canaliculi => bile ductules => bile ducts => common hepatic duct => cystic duct => common bile duct => duodenum

78
Q

Bile composition will be modified significantly as it travels along intra & extrahepatic bile ducts & will be concentrated in the…?

A

Gallbladder

79
Q

What enhances the absorptive surface of the Gallbaldder?

A

Numerous prominent folds

80
Q

What is the Gallbladder continuous with?

A

Cystic duct

81
Q

Mucosa of Gallbladder?

A
  • Simple columnar epithelium
  • Lamina propria (lots of elastic and collagen fibers)
82
Q

Thin muscularis of Gall Bladder?

A

Muscle fibers oriented in several directions

83
Q

Serosa of Gall bladder

A

Simple squamous epithelium

84
Q

Functions of Gallbladder?

A
  • Storage of bile until it’s needed in the duodenum
  • Bile concentration
85
Q

When does emptying of the Gallbladder occur?

A

When food digestion begins in upper GI tract (especially fatty foods)

86
Q

What regulated Gallbladder emptying?

A
  • CCK (most potent)
  • Ach-secreting nerve fibers from vagus nerve and ENS
87
Q

Diffuse remodeling of the liver into parenchymal nodules surrounded by fibrous bands and variable degree of vascular shunting?

A

Liver cirrhosis

88
Q

Leading causes of liver cirrhosis? (4)

A
  • Chronic Hep B
  • Chronic Hep C
  • Nonalcoholic fatty liver disease
  • Alcoholic liver disease
89
Q

What kind of cells become activates and differentiate into highly fibrotic myofibroblasts in cirrhotic liver?

A

Stellate cells

90
Q

What are stellate cells activated by?

A
  • Inflammatory cytokines
  • ROS
  • Toxins
  • Interactions with ECM
91
Q

What is stellate cell differentiation stimulated by?

A

Signals transmitted by PGDF-Beta and cytokines

92
Q

Cirrhosis pathogenesis? (4)

A
  • Stellate cells deposit ECM
  • Loss of sinusoidal endo. cells
  • Hepatocyte loss = dense fibrous septa
  • Surviving hepatocytes form nodules to try and restore liver
93
Q

Symptoms of cirrhosis?

A
  • Mostly asymptomatic
  • Can be: anorexia, weight loss, weakness
94
Q

Is reversal of cirrhosis possible?

A

Yes but it will often progress to liver failure

95
Q

Complications fo cirrhosis?

A
  • Progression to liver failure
  • Jaundice, nausea, vomiting
  • Hepatic encephalopathy
  • Hepatocellular carcinoma
96
Q

Most common biliary tract disease?

A

Cholelithiasis (gall stones)

97
Q

Two main types of Cholelithiasis (gallstones)?

A
  • cholesterol stones (crystalline cholesterol monohydrate)
  • Pigment stones (bilirubin Ca salts)
98
Q

Risk factors for gallstones?

A
  • Sex (F > M)
  • Age (middle-older age)
  • Environmental factors (estrogen)
  • Obesity and rapid weight loss
99
Q

Pathogenesis of cholesterol stones?

A

Cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation)

100
Q

______ of mucus in the gallbladder traps the nucleated crystals, leading to their aggregation into stones

A

Hypersecretion

101
Q

Pathogenesis pf pigment stones is associated with? (3)

A
  • Excessive bilirubin production
  • Ileal disease
  • Infection of GB
102
Q

Pain that can be excruciating and constant or “colicky”, that is caused by biliary obstruction

A

Biliary pain

103
Q

Where might biliary pain radiate to?

A

Right scapula

104
Q

Inflammation of the Gallbladder in association with stones might cause what?

A

Pain

105
Q

Complications of gallstones?

A

Progression into cholecystitis

106
Q

Acute inflammation of the gallbladder, precipitated 90% of the time by obstruction of the neck or cystic duct

A

acute cholecystitis

107
Q

One of the most common indications for abdominal surgery & reason for emergency cholecystectomy

A

acute cholecystitis

108
Q

Symptoms of acute cholecystitis?

A
  • Begins with progressive right upper quadrant or epigastric pain
  • mild fever, anorexia, tachycardia, sweating, nausea, and vomiting
109
Q

What does acute cholecystitis increase your risk for?

A

Carcinoma of the gallbladder

110
Q

What does elevated bilirubin result in?

A
  • Jaundice - yellow skin
  • Icterus - yellow sclera
111
Q

What can etiology of Jaundice be divided into? (3)

A
  • Pre-hepatic causes
  • Intra-hepatic causes
  • Post-hepatic causes
112
Q

Pre-hepatic cause of jaundice?

A

Excessive extrahepatic production of bilirubin

113
Q

Intra-hepatic causes of jaundice? (3)

A
  • Reduced hepatocyte uptake
  • Impaired conjugation
  • Reduced hepatocellular excretion
114
Q

Post-hepatic cause of jaundice?

A

Impaired bile flow (duct obstruction)

BMS150 Post-MT2 (17 decks)

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