6 Functions of the Liver
A. Storage (glycogen, fats, proteins, vitamins)
B. Production of cellular fuel (glucose, fatty acids and keto acids)
C. Production of plasma proteins and clotting factors
D. Metabolism of drugs and toxins
E. Filter function…breakdown RBC (Kupffer cells)
F. Production and secretion of bile
Glisson Capsule
- Surrounds liver contains BV, nerves, lymphatics
Bile canaliculi
are located in plates of hepatocytes and drain into small bile ducts
a. Small bile ducts eventually drain into R/L hepatic ducts → common hepatic duct → common bile duct → duodenum (via hepatopancreatic ampula/sphincter of Oddi)
Lobule
= functional unit of liver
- Hepatocytes are arranged radially around central vein
a. Capillaries (sinusoids) are located between the hepatocytes
b. Sinusoids receive blood from both hepatic artery and hepatic portal vein
c. Sinusoids then drain into central vein which drains into hepatic veins and then into IVC
Various immune/defense cells line the sinusoid
Kupffer Cells
Stellate Cells
Pit Cells
Disse Space
Kupffer Cells
• Macrophage (phagocytic) cells that line the sinusoids
• Function:
(i) phagocytic cells – RBC breakdown (bilirubin production)
• Clinical:
(i) Early response to liver injury/pathology
Stellate Cells
• Contractile cells located in perisinusoidal space
• Normal: lay dormant (store vitamin A)
• Pathology: stellate cells become activated
• Function when activated:
(i) contraction/relaxation regulate sinusoidal blood flow
(ii) production of scar tissue (collagen) in development of cirrhosis
Pit Cells
• Produce interferon and other immune defense substances
• Function:
(i) “first line of defense” against tumor formation
(ii) cytoctoxic effect on tumor cells
Disse Space
• The interstitial space between hepatocytes and sinusoids that drains into lymphatic vessels
Bile
A. Produced in the liver, secreted into duodenum and either excreted or re-absorbed back to liver
B. 500-600 ml produced each day
C. pH = 7.6-8.6
What is Bile?
- Alkaline, yellow fluid that is made of mostly water and electrolytes
- Bile also contains organic compounds (bile salts, cholesterol, bilirubin, phospholipids)
a. bile salts
• Bile salts are the major organic compound found in bile
• Bile salts are conjugated bile acids
• Bile acids are necessary for fat digestion (absorption)
(i) Bile is an emulsifying agent to assist in breakdown of fats for absorption in small intestine and formation of micelles
b. phospholipids (mostly lecithin)
c. cholesterol
d. bilirubin
e. other endogenously produced/ingested compounds
• drugs or metabolic by-products metabolites
• proteins involved in GI regulation
Bile secretion: hepatoenteric pathway
- Bile secreted into canaliculi
- Canaliculi eventually drain into R/L hepatic duct and the common hepatic duct
- During fasting
a. 75% will flow into gall bladder
• Gallbladder will concentrate bile
b. 25% will” continue on” and flow into duodenum via common bile duct - During feeding
a. Gall bladder contracts via CCK and vagal stimuli
• CCK and vagal will also relax sphincter of Oddi to allow flow
F. Bile formation and utilization in Liver Circulation
a. Hepatocytes synthesize primary bile acids
• CCK, secretin stimulate bile production
• Synthesized from cholesterol
b. Bile acids are “converted” into bile salts
• Primary bile acids are conjugated to become bile salts (water soluble)
c. Bile salts are secreted into canaliculi which “pulls along” the other bile components
• water and electrolytes follow osmotic shift into canaliculi
d. Bile (containing bile salts) secreted into duodenum
Bile formation and utilization in Duodenum Circulation
a. If sufficient amount of conjugated bile salts are in duodenum then they will emulsify fats droplets and physically arrange into formation called micelles
• Micelles = “Clumps” (aggregates) of bile salts, fat droplets, fat soluble vitamin, cholesterol, and phospholipids that form a circle with hydrophilic-ends on outside
b. As the micelles release fats for absorption, the bile salts are released and continue to the terminal ileum/colon
- Terminal ileum/colon
a. 90% are absorbed and transported back to the liver
b. 10 % continue to the rectum and are excreted
Bilirubin pathway
A. Bilirubin is byproduct of RBC breakdown that needs to be excreted
1. RBC lifespan approximately 120 days
Bilirubin pathway– RBC
- RBCs breakdown in spleen, liver (Kupffer cells) and throughout vascular system
- RBC broken down with hemoglobin further divided
a. Globin: is further broken down into amino acids
b. Heme: is broken down into iron and bilverdin
• Iron is stored (in liver) and recycled into RBC formation (bone marrow)
• Biliverdin is further broken down into bilirubin and released in the plasma
Bilirubin pathway– Unconjugated bilirubin formation in plasma
- In the plasma bilirubin attaches to albumin and is unconjugated bilirubin (fat soluble)
- The unconjugated bilirubin travels to the liver
a. NOTE: The unconjugated form (fat soluble) can’t be excreted from the kidney
Bilirubin pathway– Unconjugated bilirubin is conjugated in the liver
- the unconjugated bilirubin circulates through the hepatocytes and is conjugated
a. The conjugated bilirubin is water soluble which allows it to be excreted - the newly formed conjugated bilirubin mixes with bile in canaliculi and is secreted into duodenum or stored in gallbladder
Intestines (formation of urobilinogen)
- Conjugated bilirubin secreted into duodenum
- Bacteria in the intestines “deconjugate” the bilirubin into urobilinogen
- Three pathways of urobilinogen
a. Reabsorbed into blood stream
• excreted in the urine
• recycled in the liver
b. Remains in colon and is excreted in stool (responsible for dark stool color)
Urobilinogen in urine
a. Normal values: 0-4 mg/24 hrs
b. Increased values: pre-hepatic jaundice
c. “Decreased” values: post-hepatic jaundice
Mechanical pathways of jaundice (hyperbilirubinemia)
bilirubin pigment causes yellowing (eyes, bruising, etc…)
a. Yellowish pigmentation of skin (tissues) & conjunctival membranes due to excessive bilirubin in bloodstream (hyperbilirubinemia)
b. Jaundice(icterus) is a symptom/sign of disease/pathology affecting the metabolism/excretion of bilirubin
• Jaundice IS NOT a specific disease/pathology
Classification of Jaundice
a. Jaundice is subdivided into three classifications depending on the location of the pathology that is disrupting bilirubin metabolism/elimination
• Pre-hepatic: pathology “prior to” the liver (increased RBC breakdown)
(i) Genetic diseases (Gilbert’s syndrome, sickle cell anemia, thalassemia, etc…), kidney disease
• Intra-hepatic: pathology located within the liver (liver’s ability to conjugate bilirubin is impaired)
(i) Ex: cirrhosis, hepatitis, liver toxicity, etc…
• Post-hepatic: pathology located “after” the liver (impaired transport of conjugated bilirubin to GI tract)
(i) Ex: gallstones or pancreatic pathology that blocks the bile ducts
Lab Profiles of Jaundice
a. No single lab test will specifically DDx between classifications of jaundice
b. Multiple lab tests are needed to establish Dx
• requires “whole picture” assessment of all LFT (liver function tests), urine and stool analysis
• different patterns of LFT (liver function tests), urine and stool analysis are characteristic of each jaundice classification (location)
