Physiology and Pathology: Liver & Gallbladder Flashcards
Livers special role in the circulatory system - receives portal blood that drains into…? (5)
- Stomach
- Small intestine
- Large intestine
- Pancreas
- Spleen
What is the livers important role in immunology?
Kupffer cells (in liver) = up to 80% of mononuclear phagocyte system
4 lobes of the liver?
- Right lobe
- Left lobe
- Quadrate lobe (inferior)
- Caudate lobe (posterior)
Which lobe of the liver is never palpable?
Caudate lobe
Important ligaments of the liver? (4)
- Coronary lig.
- Falciform lig.
- Round lig.
- Ligamentum venosum
Ligaments that anchors the liver to the diaphragm?
Coronary ligaments
Ligament that separates right and left lobes of liver?
Falciform ligament
Ligament found on free border of falciform ligament separates quadrate and left lobe
Round ligament
Other name for round ligament?
Ligamentum teres
What is the embryological significance of the round ligament (ligamentum teres)?
Remnant if the left umbilical vein - connects liver to umbilicus
Ligament that separates the caudate and left lobe
Ligamentum venosum
What is the embryological significance of the ligamentum venosum?
Fibrous remnants of ductus venosus from fetal circulation
What separates quadrate lobe and right lobe?
Gallbladder
Liver receives oxygenated blood from the ________
Hepatic artery
Liver receives deoxygenated, nutrient rich blood from the ________
Hepatic portal vein
Where both arteries in the liver enter?
Porta hepatis
What is the Porta hepatis an opening for? (3)
- Hepatic artery
- Portal vein
- Common hepatic duct
Three main histological components of liver?
- Hepatocytes
- Bile canaliculi/cholangiocytes
- Hepatic sinusoids
Major functional cell of the liver?
Hepatocyte
Hepatocytes are specialized _______ cells arranged into _______
epithelial; hepatic laminae
Hepatic laminae structure?
Highly branched plates of hepatocytes bordered by hepatic sinusoids
Grooves in the cell membrane of neighboring hepatocytes provide space for…?
bile canaliculi
What are hepatocytes arranged into?
Lobules
Hepatic lobules surround a ______ and are cornered by ______
central vein; portal triad
What does the central vein drain? Where does it empty?
- Drains: hepatic sinusoids
- Empties into: Hepatic vein
What is the Portal triad? What are the arteriole and venule branches?
- It’s a bile duct
- Art: branch of hepatic art
- Ven: branch of portal vein
Small ducts found between hepatic laminae that collect bile?
Bile canaliculi
Lining of bile ductules and ducts?
Cholangiocytes
Capillary system specific to the liver?
Hepatic sinusoids
Hepatic sinusoids are _______ discontinuous endothelium
Fenestrated
What are hepatocytes separated from sinusoids by?
Space of Disse
What mixes in the hepatic sinusoids?
Blood from the portal vein and hepatic artery
what are normally found in a quiescent state in the space of Disse?
Hepatic stellate cell/Ito cell
Major cell type in liver fibrosis?
Hepatic stellate cell/Ito cell
When do hepatic stellate cells become active?
When there is damage
What do hepatic stellate cells do in response to damage?
Secrete collagen and extracellular matrix = scar tissue formation
Hepatic stellate cells have several long protrusions that ________
Wrap around sinusoids
What do hepatic stellate cells store?
Lipid droplets in cell body containing Vitamin A retinol esters
Resident macrophages of the liver?
Kupffers cells
Where are Kupffer cells derived from?
Circulating monocytes
Functions of Kupffer cells? (5)
Phagocytose:
- Old RBCs
- Hemoglobin
- Particulate matter
- Cellular debris
- Microorganisms
Hepatocytes, bile duct system and hepatic sinusoids can be organized into functional units called ______
Hepatic acinus
What is hepatic acinus?
Ovular mass that includes portions of 2 neighbouring hepatic lobules
Two axes of hepatic acinus?
- Short: branches of portal triad
- Long: connects 2 central veins to short axis
Hepatocytes are arranges into 3 zones around the short axis, what are they?
- Zone 1 - most O2
- Zone 2
- Zone 3 - least O2
T/F: Hepatocyte function differs based on zone within hepatic acinus
True
Hepatocytes in zone 1 specialize in…?
Oxidative metabolism
Hepatocytes in zone 3 specialize in…?
Biotransformation of drugs
Liver functions? (4)
- Biotransformation and degradation
- Bilirubin conjugation
- Storage/synth of nutrients
- Bile production
Why does the liver have to process lipophilic chemicals into polar, water soluble metabolites?
Need to be water soluble to transport them through blood or excrete them into bile
4 major steps of biotransformation and degradation
- Imports compound
- Transport w/in cell
- Chemically modify/degrade
- Excretion into bile
What kind of pumps at the basolateral membrane provides energy for transporting a wide variety of solutes into hepatocyte?
- Na-K pump
- Organic anion-transporting polypeptides (OATPs)
- Organic cation transporter (OTC)
What are OATPs responsible for?
Uptake of a variety of endogenous & exogenous amphipathic compounds (bile acids, biliribun, PGs)
What are OTCs responsible for?
Uptake of a variety of lipophilic organic cations (acyclovir, epi, norepi, histamine)
Two phases of modification stage?
- Phase I - Redox by CYP450
- Phase II - conjugation
Oxidation-reduction reactions that can happen in phase I?
Hydroxylation, dealkylation, dehalogenation
What happens in the conjugation phase? Why?
Addition of highly hydrophilic compound = water soluble for transport
What compounds are typically involved in conjugation?
Glutathione, sulfate, glucuronate
What adds glucuronic acid?
Uridine diphosphate gluconosyntransferase (UGT)
Overall, what is the sequence of reactions occurring in the modification stage of biotransformation?
RH => ROH => RO-conjugate
What is the conjugated compound transported out of the hepatocyte into?
- Blood via sinusoidal memb
- Bile across canalicular memb
What does transport of the conjugated compound out of the hepatocyte require?
ATP-binding cassette (ABC)
Conjugated bilirubin will be carried to the liver by what?
Albumin
In the liver, bilirubin will be ______, and what will be added?
Conjugated; glucuronic acid
Bilirubin glucuronide will be excreted into what?
Bile
What do bacteria in the terminal ileum and colon convert some of the conjugated bilirubin into?
Back into bilirubin
What is the bilirubin in the colon/terminal ileum then converted to?
urobilinogen
What are two things that can happen to urobilinogen?
- convert to stercobilin (pigment of feces)
- reabsorbed and filtered by kidneys (gives urine yellow colour)
What are nutrients brought to the liver by?
Hepatic portal vein
Depending on metabolic requirements, what can happen to the substrates brought to the liver? (3)
- Stored by hepatocytes
- Released unbound into circulation
- Bound to carriers and released into circulation
Essential substances the liver can synthesize?
Albumin, coagulation factors, plasmaproteins
Two functions of bile production by the liver?
- Elimination of exogenous and endogenous waste
- Promotes digestion and absorption of lipids from intestines
What is bile initially synthesized from? What does this yeild and what do they become?
Cholesterol - primary bile acids
- will be conjugated and become primary bile salts
In the terminal ileum of the colon, be ______ by bacteria and reabsorbed. These become what?
Dehydroxylated; secondary bile salts
Other components of Bile?
- Phospholipids
- IgA
- Excretory waste products
Excretory waste products in bile? (5)
- Cholesterol
- Bile pigment (bilirubin)
- Lipophilic drugs and metabolites
- Oxidized GSH
- Trace minerals
Bile flow pathway?
Hepatocyte => bile canaliculi => bile ductules => bile ducts => common hepatic duct => cystic duct => common bile duct => duodenum
Bile composition will be modified significantly as it travels along intra & extrahepatic bile ducts & will be concentrated in the…?
Gallbladder
What enhances the absorptive surface of the Gallbaldder?
Numerous prominent folds
What is the Gallbladder continuous with?
Cystic duct
Mucosa of Gallbladder?
- Simple columnar epithelium
- Lamina propria (lots of elastic and collagen fibers)
Thin muscularis of Gall Bladder?
Muscle fibers oriented in several directions
Serosa of Gall bladder
Simple squamous epithelium
Functions of Gallbladder?
- Storage of bile until it’s needed in the duodenum
- Bile concentration
When does emptying of the Gallbladder occur?
When food digestion begins in upper GI tract (especially fatty foods)
What regulated Gallbladder emptying?
- CCK (most potent)
- Ach-secreting nerve fibers from vagus nerve and ENS
Diffuse remodeling of the liver into parenchymal nodules surrounded by fibrous bands and variable degree of vascular shunting?
Liver cirrhosis
Leading causes of liver cirrhosis? (4)
- Chronic Hep B
- Chronic Hep C
- Nonalcoholic fatty liver disease
- Alcoholic liver disease
What kind of cells become activates and differentiate into highly fibrotic myofibroblasts in cirrhotic liver?
Stellate cells
What are stellate cells activated by?
- Inflammatory cytokines
- ROS
- Toxins
- Interactions with ECM
What is stellate cell differentiation stimulated by?
Signals transmitted by PGDF-Beta and cytokines
Cirrhosis pathogenesis? (4)
- Stellate cells deposit ECM
- Loss of sinusoidal endo. cells
- Hepatocyte loss = dense fibrous septa
- Surviving hepatocytes form nodules to try and restore liver
Symptoms of cirrhosis?
- Mostly asymptomatic
- Can be: anorexia, weight loss, weakness
Is reversal of cirrhosis possible?
Yes but it will often progress to liver failure
Complications fo cirrhosis?
- Progression to liver failure
- Jaundice, nausea, vomiting
- Hepatic encephalopathy
- Hepatocellular carcinoma
Most common biliary tract disease?
Cholelithiasis (gall stones)
Two main types of Cholelithiasis (gallstones)?
- cholesterol stones (crystalline cholesterol monohydrate)
- Pigment stones (bilirubin Ca salts)
Risk factors for gallstones?
- Sex (F > M)
- Age (middle-older age)
- Environmental factors (estrogen)
- Obesity and rapid weight loss
Pathogenesis of cholesterol stones?
Cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation)
______ of mucus in the gallbladder traps the nucleated crystals, leading to their aggregation into stones
Hypersecretion
Pathogenesis pf pigment stones is associated with? (3)
- Excessive bilirubin production
- Ileal disease
- Infection of GB
Pain that can be excruciating and constant or “colicky”, that is caused by biliary obstruction
Biliary pain
Where might biliary pain radiate to?
Right scapula
Inflammation of the Gallbladder in association with stones might cause what?
Pain
Complications of gallstones?
Progression into cholecystitis
Acute inflammation of the gallbladder, precipitated 90% of the time by obstruction of the neck or cystic duct
acute cholecystitis
One of the most common indications for abdominal surgery & reason for emergency cholecystectomy
acute cholecystitis
Symptoms of acute cholecystitis?
- Begins with progressive right upper quadrant or epigastric pain
- mild fever, anorexia, tachycardia, sweating, nausea, and vomiting
What does acute cholecystitis increase your risk for?
Carcinoma of the gallbladder
What does elevated bilirubin result in?
- Jaundice - yellow skin
- Icterus - yellow sclera
What can etiology of Jaundice be divided into? (3)
- Pre-hepatic causes
- Intra-hepatic causes
- Post-hepatic causes
Pre-hepatic cause of jaundice?
Excessive extrahepatic production of bilirubin
Intra-hepatic causes of jaundice? (3)
- Reduced hepatocyte uptake
- Impaired conjugation
- Reduced hepatocellular excretion
Post-hepatic cause of jaundice?
Impaired bile flow (duct obstruction)
