Unit VI- Liver and Gallbladder

Question 1

Liver Synthesis

Answer 1

• syntheses circulating plasma proteins
• albumins
• lipoproteins especially VLDLs
• glycoproteins including haptoglobin, transferrin and hemopexin involved in iron transport
• Prothombin and fibrinogen
• non-immune alpha and beta globulin

Question 2

Liver overview

Answer 2

• liver is the second largest organ of the body (1,500 grams in adult)
• enclosed in fibrous connective tissue (Glisson’s capsule)
• it is divided into 4 lobes (right, left, quadrate, and caudate)

Question 3

Liver Storage

Answer 3

• storage and conversion of several vitamins and iron
• Vitamin A
• Vitamin D
• Vitamin K
• iron storage

Question 4

Degradation of Drugs and Toxins

Answer 4

-the hepatocytes oxidize or conjugate many water insoluble drugs and toxins to make them more easily removable by the kidney

Question 5

Liver and Metabolism

Answer 5

• involved in glycogen storage
• cholesterol metabolism
• urea synthesis

Question 6

Exocrine function in Bile Production

Answer 6

• bile is an exocrine secretion of the liver that includes the wastes of erythrocyte destruction and bile salts that act as emulsifying agents to aid gut absorption
• bile is delivered to the duodenum

Question 7

Endocrine like function of liver

Answer 7

-the liver modifies the action of hormones released by other organs including vitamin D and thyroxine conversion and the production of growth hormone-releasing factor

Question 8

Hepatocyte ultrastructure and major functions

Answer 8

• RER is primarily engaged in synthesis of plasma proteins for release into the perisinusoidal space
• potentially toxic compounds, bilirubin (bound to albumin) and bile acids are taken up from the perisinusoidal space, processed by enzymes in the tubulovesicular system of the SER, and secreted into the bile canaliculi
• glucose is taken up from the perisinusoidal space and stored in glycogen granules, with the process reversed when glucose is needed

Question 9

Blood Supply to the Liver

Answer 9

• liver has a dual blood supply
• 75% is supplied by the hepatic portal vein. This blood is depleted of oxygen, but rich in nutrients, toxins, and hormones
• 25% is supplied by the hepatic artery that carries oxygenated blood
• the blood is mixed shortly before it enters the hepatic sinusoids

Question 10

Hepatic portal vein

Answer 10

• supplies approximately 75% of the liver’s blood volume
• blood is rich in nutrients and toxic materials from the intestine, contains blood cell breakdown products from the spleen, and has endocrine secretions of the pancreas and enteroendocrine cells of the GI tract
• this venous blood is largely depleted of oxygen

Question 11

Hepatic artery

Answer 11

• carries oxygenated blood that mixes with the venous blood just before it enters the hepatic sinusoids
• it supplies approximately 25% of the liver’s blood volume

Question 12

Portal triad

Answer 12

• branches of the hepatic artery and portal vein travel with draining branches of the bile duct forming the portal triad
• these are present in connective tissue (Glisson’s capsule) at the angles of the hexagonal liver lobule
• branches of the hepatic artery irrigate the structures in the portal canal
• lymphatic vessels and nerve branches can also be found in these portal canal areas

Question 13

Hepatic sinusoids

Answer 13

• in intimate contact with the hepatocytes
• the sinusoids are radially arranged around the central vein (terminal hepatic venule) and empty into central vein
• the central vein gets larger as it progresses along the lobule and empties into the sublobular veins which join to form the hepatic veins that empty into the inferior vena cava
• the sublobular veins and the hepatic veins travel alone so they can be distinguished from the portal veins that are members of the portal triads

Question 14

Blood Supply Summary

Answer 14

• Portal vein
• portal venules
• sinusoids
• terminal hepatic venules
• sublobular veins
• hepatic veins
• inferior vena cava
• Hepatic artery
• Hepatic arterioles
• Sinusods
• Terminal hepatic venules
• Sublobular veins
• Hepatic veins
• Inferior vena cava

Question 15

Liver structural components

Answer 15

• parenchyma
• connective tissue stroma
• sinusoidal capillaries (sinusoids)
• perisinusoidal spaces (spaces of Disse)

Question 16

Parencyma

Answer 16

-consists of one cell thick plates of hepatocytes separated by sinusoidal capillaries

Question 17

Connective tissue stroma

Answer 17

-that is continuous with Glisson’s capsule and branches into the smallester portal canals

Question 18

Sinusoidal capillaries (sinusoids)

Answer 18

separate the plates of hepatocytes

Question 19

Perisinusoidal spaces (spaces of Disse)

Answer 19

-that lie betwen the sinusoidal endothelium and the hepatocytes

Question 20

Classic Liver Lobule

Answer 20

• hexagonal cylinder of tissue of 0.7 x 2.0 mm
• the terminal hepatic venule is at the center of the lobule
• in humans, the classic lobule is visualized by drawing lines connecting the portal canals and a central vein
• in other species in the pig, the classic lobule is easily recognized because the portal canals are connected by thick interlobular connective tissue

Question 21

Portal lobule

Answer 21

• emphasizes the exocine functions of the liver
• the major exocrine function is bile secretion, so the portal lobule has a portal canal at its center
• a triangle is formed by connecting lines between the three closest center veins

Question 22

Liver acinus

Answer 22

• is a football shape whos long axis is a line drawn between two central veins
• the short axis is the line between adjacent portal canals that lies between these central veins
• blood perfusion, metabolic activity and liver pathology
• separated into zones

Question 23

Zone 1

Answer 23

• contains the hepatocytes that are the first to recieve oxygen, nutrients and toxins from the sinusoidal blood
• these hepatocytes die last when circulation is impaired and are the first to regenerate
• most peripheral
• perilobular region: oxygen, extrahepatic hormones, key glucose liberating enzymes, key fatty acid oxidation

Question 24

Zone 3

Answer 24

• hepatocyes are more central
• first to show ischemic necrosis and first to show fat accumulation
• CHF picture, less O2 to the tissue, damage in central area
• centrolobular region- key glycolysis enzymes

Question 25

Zone 2

Answer 25

-hepatocytes are intermediate in character between zone 1 and 3 cells

Question 26

Hepatic sinusoids

Answer 26

• discontinuous sinusoidal capillaries with large fenestrae and gaps between endothelial cells
• Kupffer cells form part of wall and occupy lumen

Question 27

Kupffer cells

Answer 27

• extend into the lumen
• derived from monocytes and are members of the mononuclear phagocytotic system (MPS)
• destroy aged erythrocytes (along with spleen)
• digest hemoglobin, and destroy bacteria
• make up 15% of the liver cell population
• has to be stained with the special dye

Question 28

Perisinusoidal space (space of Disse)

Answer 28

• site of exchange between blood and liver cells
• Ito cells (hepatic stellate cells) that store vitamin A reside in this space
• hepatocytes have numerous microvilli projecting into this space (increase SA 6x)
• under certain conditions like chronic inflammation of cirrhosis, the Ito cells lose this storage ability and transform into myofibroblasts that synthesis the colalgen that results in liver fibrosis

Question 29

Hepatocytes

Answer 29

• are large, polygonal (6 or more) cells with a diameter of 20-30 microns. They make up to 80% of the liver cell population
• large spherical, centrally located nuclei with prominent nucleoli
• binucleate and polyploid nuclei develop with age
• the adult liver is mostly tetraploid. Well developed nucleoli
• 5 month life span- some hepatocyes can be replaced by regeneration- aging reduces this capacity

Question 30

Cytoplasmic components of hepatocyte

Answer 30

• numerous mitochondria
• the Golgi apparatus is elaborate and each cell may have up to 50
• both the rough and smooth ER are highly developed
• sER varies with metabolic activity- EtOH produce sER hypertrophy
• clinically newborns can have underdeveloped sER (neonatal hyperbilirubinemia) where bilirubin is not converted to the water-soluble bilirubin glucuronide
• treated with blue light from ordinary fluorescent bulbs that transforms unconjuated bilirubin to a water soluble photoisomer
• peroxisomes and lysosomes are also numerous
• glycogen in the liver provides a depot for glucose that is mobilized if blood glucose levels fall

Question 31

Bile Tree

Answer 31

• bile flows outward from the center of the classic liver lobule
• bile canaliculi are 0.5 microns in diameter and formed by adjacent hepatocytes

Question 32

Bile canaliculus

Answer 32

• small canal formed between the surfaces of adjacent hepatocytes
• it is about 0.5 microns in diameter and isolated by tight junctions
• small microvilli rich in ATPase and other alkaline phosphatases project into the lumen
• empty into intrahepatic ductals

Question 33

-Intrahepatic ductules (canals of Hering)

Answer 33

• within the lobule, but close to the portal canal
• these ductules are made of cuboidal epithelial cells and they and they join with the interlobular bile ducts that are part of the portal triad

Question 34

Bile

Answer 34

• adult liver secretes 1 liter/day
• composition: water, phospholipids, cholesterol, bile salts, bile pigments, electrolytes
• bile salts such as cholic acid are emulsifying agents that aid in the digestion and absorption of lipids from the gut
• about 90% of salts are recycled by gut reabsorption, portal vein transport, and hepatocyte resecretion
• cholesterol, lecithin, electrolytes, and water are recycled
• the bile pigment bilirubin glucoronide is excreted with the feces
• CCK, gastrin, motilin, and parasympathetic stimulation increase bile flow

Question 35

Gallbladder

Answer 35

• can store bile and concentrate it up to ten fold
• is a hollow, pear-shaped organ that can hold about 50 ml
• it has a single duct (the cystic duct) that both receives diluted bile from the liver and discharges concentrated bile to the duodenum via the common bile duct and the sphincter of Oddi

Question 36

Histology of Gallbladder

Answer 36

• mucosa of the gallbladder consists of simple columnar epithelial cells with apical microvilli, complex lateral placations, and concentrations of mitochondria all typical of an organ specialized for absorption of electrolytes and water. It has lamina propria, but no muscularis mucosae
• the mucosa of the empty gallbladder has rugae or folds that flatten out when the gallbladder is full. Invaginations of the mucosa form diverticula (Rokitansky-Aschoff sinuses) that can extend into the muscularis. These diverticular increase with age
• the muscularis has smooth muscle bundles in rather random orientations whose contraction empties the contents into the cystic duct. The gallbladder has an adventitia where it is attached to the liver and serosa on its free surface

Question 37

Path of bile

Answer 37

• left and right hepatic ducts merge to form a common hepatic duct
• common heptatic and cystic ducts merge to form a common bile duct
• main pancreatic duct merges with common bile duct at the hepatopancreastic ampulla which extends into the duodenum
• bile and pancreatic juices enter duodenum at major duodenal papilla