Phys: Gallbladder and Bile

Question 1

hepatic blood supply

Answer 1

1 a. Hepatic artery (25%): Arterial blood which provides the liver’s O2 supply and metabolites for hepatic processing

b. Hepatic portal vein (75%): venous blood draining the stomach, digestive tract, pancreas, and spleen for processing and storage of newly absorbed nutrients
2. Hepatic vein: Blood leaves the liver via hepatic vein

Question 2

Functions of liver

Answer 2

1. Metabolism of major nutrients: carbs, lipids, proteins
2. synthesis of plasma proteins, albumins, glucose, chol, FA’s
3. Storage of glycogen, fats, iron, vitamins
4. *Detox: steroids, hormones, drugs, toxins
5. Inactivation: removes foreign particulate matter by Kuppfer macrophage cells: bacteria, endotoxins, parasites, agin RBC’s
6. Activation: convert hormones and vitamins into more active form hydroxylation of vitamin D
7. Bile production

Question 3

Bile

Answer 3

• “gall”
• green-yellow from bilirubin
• bitter, neutral or slightly alkaline fluid synthesized by the liver
• consists of salts, proteins, cholesterol, hormones, enzymes and bilirubin

Question 4

Bilirubin

Answer 4

• breakdown product of heme from Hgb

- excreted by liver in bile

Question 5

bile secretion

Answer 5

hepatocytes –> bile canaliculus –> bile duct (periphery of lobule) –> common bile duct –> duodenum

Question 6

hepatocyte lobule

Answer 6

• functional units of liver, hexagonal arrangements surrounding a central vein.
• At each of the 6 corners of the lobule there are 3 vessels (hepatic artery, hepatic portal vein, bile duct)

Question 7

sinusoid

Answer 7

: expanded capillary spaces between rows of hepatocytes

- hepatic artery & portal vein flows blood from sinusoids to central veins to hepatic veins

Question 8

bile canaliculus

Answer 8

• bile carrying channels runs between sinusoids and within each hepatic plate
• Each hepatocyte is in contact with a sinusoid on one side and bile cannaliculus on other side

Question 9

cells of liver:

Answer 9

parenchyma composed of hepatocytes (95%)
- sinusoidal space contains: 
2% Kuppfer (phagocytic cells)
1% Stellate (Ito) cells: fibroblasts
2% endothelial cells

Question 10

Stellate cells

Answer 10

= Ito cells
- when inflammation occurs: Ito cells turn into myofibroblasts, produce collagen, liver becomes fibrotic, constricts blood flow and this blood supply results in necrosis –> cirrhosis

Question 11

Space of Disse

Answer 11

• space between sinusoid and hepatocyte
• stellate cells present here
• Kuppffer cells cleanse blood of bacteria, toxins, parasites, aging RBC’s as it passes through
• albumin is secreted here

Question 12

Portal acinus

Answer 12

lobular arrangement purposed around the supply of oxygenated blood to hepatocytes

Question 13

sphincter of Oddi

Answer 13

• regulates flow out of common bile duct and pancreatic duct
• prevents bile from entering the duodenum
• after meal, this relaxes and bile enters the duodenum due to CCK and ACh

Question 14

Bile flow?

Answer 14

Bile produced in hepatocytessecreted
into canaliculbile ductulescommon
ductgall bladderbile duct
small intestine

Question 15

2 components to bile secretion:

Answer 15

1. Hepatocyte cells: secrete bile acids, cholesterol.
2. Secretory eptihelial cells: located in ducts and ductules: secrete watery solution of sodium and bicarb in response to secretin

Question 16

secretin

Answer 16

• stimulates cholangiocytes of ductules and ducts to secrete bicarb. into ducts and initial bile
• secretin, glucagon, VIP are all stimulatory to bile secretion

Question 17

flow of bile?

Answer 17

hepatic cells - minute bile canaliculi -
interlobular septa – terminal bile ducts –
larger ducts – hepatic and common bile duct –
duodenum or via cystic duct into gallbladder.

Question 18

3 steps of bile formation

Answer 18

• canalicular bile is active and isotonic
  1. Hepatocytes actively secrete bile into the bile canaliculi: The hepatocytes conjugate most of primary bile acids to small molecules such as glycine and taurine before secreting them into the bile.
  2. Intrahepatic and extrahepatic bile ducts not only transport this bile but also secrete into it a watery, HCO3−-rich fluid

These first two steps may produce ∼1000 mL/day of so-called hepatic bile.

3. Half the hepatic bile-(500 mL/day) is diverted to the gallbladder, which stores the bile and iso-osomotically removes salts and water

Question 19

bile compensation

Answer 19

67% bile acid
22% phospholipids
4% cholesterol
.3% bilirubin
4.7% protein (includes bicarb.)

Question 20

Bile salts

Answer 20

Bile Salts (cholates, chenodeoxycholate, deoxycholate): produced by hepatic metabolism of cholesterol and excreted into bile. 
- Bile salts in bile act as detergents to dissolve dietary fat for absorption

Disruption of bile excretion disrupts fat absorption & causes malabsorption:
- Patients develop diarrhea because of the resultant steatorrhea and then develop associated deficiencies of fat-soluble vitamins (A, D, E, & K)

Question 21

Cholesterol and Phospholipids

Answer 21

• hepatic secretion of cholesterol and its metabolites (bile salts) into bile is the body’s major route of cholesterol elimination.
• Bile phospholipids enhance cholesterol solubilizing properties of bile salts
• Inefficient excretion cholesterol can cause an increased serum cholesterol

Question 22

Bilirubin

Answer 22

Comprises only 0.3% bile; responsible for bile’s green-black color.
- Obstruction of bile flow leads to jaundice.

Question 23

functions of bile

Answer 23

1. Fat digestion and absorption: After eating, gallbladder contracts & releases bile acids into intestines. Digests/absorbs lipids by emulsifying and assisting through intestinal mucosa.
2. Waste product excretion: bilirubin, cholesterol, liphophilic drugs, trace minerals

Question 24

Bile salts actions in intestinal tract

Answer 24

1. Detergent action or Emulsification on fat particles.
   - decreases the S/A
   - increase agitation in intestinal tract to break fat globules
2. Absorption of:
   - Fatty acids, monoglycerides, cholesterol and other lipids by formation of small complexes called micelles (semi-soluble in chyme)

Question 25

somatostain

Answer 25

- inhibits bile flow by lowering [cAMP]i, an effect opposite that of secretin. - This inhibition may be caused by enhancing fluid reabsorption by bile ducts.

Question 26

Secretin, Glucagon and Vasoactive Intestinal Peptide (VIP)

Answer 26

increases secretion via: - Stimulates the cholangiocytes of ductules and ducts to secrete a watery, HCO−3-rich fluid - raise [cAMP]i and thus stimulate apical Cl− channels and the Cl-HCO3 exchanger. (Cl- taken into cholangiocyte from lumen, and HCO3- excreted into lumen) - A Ca2+-activated Cl− channel is also present in the apical membrane.

Question 27

Mucus

Answer 27

- secretion by gallbladder epithelial cells protects the apical surface of the gallbladder epithelium from the potentially toxic effects of bile salts. However, excessive mucin synthesis can be deleterious: - -> Cholesterol cholelithiasis (i.e., formation of gallstones made of cholesterol), a marked - increase in mucin release precedes crystal and stone formation.

Question 28

CCK

Answer 28

- presence of fatty food in the duodenum results in release of CCK - causes contraction of the gallbladder - causes relaxation of the sphincter of Oddi - increases bile flow into the duodenum

Question 29

Ach

Answer 29

secreted from vagus and intestinal enteric NS | - stimulates gallbladder less strongly than CCK

Question 30

Steps of Bile release:

Answer 30

1. acidic/fatty chyme enters duodenum, results in release of CCK and secretin from duodenal wall enteroendocrine cells 2. CCK and secretin enter blood stream 3. bile salts and secretin stimulate liver to produce bild more rapidly 4. vagal stimulation via ACh causes weak contraction of gallbladder 5. CCK causes gallbladder to contract and sphincter of Oddi to relax 6. bile salts reabsorbed into blood

Question 31

enterohepatic circulation of bile acids

Answer 31

- recirculation of the bile salts - liver makes small amount of total bile pool - majority of bile is recycled via enterohepatic circulation from terminal ileum --> hepatic portal vein --> liver - reabsorbed via diffusion and active transport in distal ileum --> portal vein. - hepatocytes reabsorb and then resecrete the bile

Question 32

Salmonella typhi

Answer 32

The gallbladder serves as “safe harbor” in the healthy carrier state for typhoid (enteric) fever.

Question 33

Cholestasis: what are three things it causes

Answer 33

- suppression of bile secretion - biliary constituents may be retained within the hepatocyte and regurgitated into the systemic circulation. - causes three major groups of negative effects: 1. regurgitation of bile components (bile acids, bilirubin) into the systemic circulation gives rise to the symptoms of jaundice and pruritus (itching). 2. cholestasis damages hepatocytes, as evidenced by the release of liver enzymes (e.g. alkaline phosphatase) into the plasma. 3. because the bile acids do not arrive in the duodenum, lipid digestion and absorption may be impaired. ***Many acute and chronic liver diseases produce cholestasis by mechanically obstructing the extrahepatic bile ducts or by impairing bile flow at the level of the hepatocytes or intrahepatic bile ducts.

Question 34

Cholelithiasis

Answer 34

formation of stones (calculi) within the gallbladder or biliary duct system

Question 35

Cholecystitis

Answer 35

inflammation of gall bladder (often due to stones remaining in gall bladder for too long)

Question 36

Cholangitis

Answer 36

inflammation of biliary ducts

Question 37

Gallstones form due to...

Answer 37

1. abnormal bile composition (too much absorption of water from bile, too much absorption of bile salts, too much cholesterol) 2. biliary stasis 3. inflammation of gallbladder

Question 38

Places where cholelithiasis can occur:

Answer 38

1. asymptomatic stone in gallbladder 2/3. stone lodged in cystic duct - causes intermittent biliary pain, can also cause cholecystitis 4. stone in cystic duct compressing into bile duct, causing Mirizzi's syndrome 5. stone in distal bile duct, causing jaundice, biliary-type pain, and risk of cholangitis/pancreatitis. obstructing ampulla of Vater. 6. stone eroding through gallbladder into duodenum: causes cholecystoenteric fistula 7. long-standing cholelithiasis resulting in gallbladder carcinoma

Question 39

Risk for gallstones?

Answer 39

Female, Fat, Fair, old age

Question 40

conditions for formation of cholesterol gall stones?

Answer 40

- supersaturation - gallbladder hypomotility - crystal nucleation - accretion within mucous layer

Question 41

cholecystectomy

Answer 41

removal of gallstones - gallstones may be present for decades before symptoms develop - larger the stone, the less likely it is to enter cystic or common ducts and obstruct - small "gravel" stones are more dangerous

Question 42

Bile acids formation

Answer 42

- The major solutes driving the primary secretion of bile are the bile acids, which are amphipathic molecules synthesized from cholesterol in the hepatocyte. - Bile acids can be modified by intestinal bacteria to yield compounds known as secondary bile acids. One of these, lithocholic acid, is relatively toxic, and so mechanisms exist to promote its elimination from the body.

Question 43

Bile production summary: see slide.

Answer 43

- hepatocytes make bile acids from cholesterol. these acids are secreted into bile canaliculus in conjugated form. Bile includes glucose and calcium as well. Glucose is actively reabsorbed from bile as it passes to biliary ductules - which also add IgA and render bile alkaline via secretion of bicarb.

Question 44

how does bile remain iso-osmolar during concentration?

Answer 44

Gallbladder storage of bile results in changes in its composition, such that bile acids become the dominant anions. Bile remains isotonic during this process as bile acid monomers are rapidly incorporated into mixed micelles. Concentration of bile results from active transport processes taking place in the lining epithelial cells.

Question 45

Bile synthesis

Answer 45

The liver converts cholesterol to the primary bile acids—cholic acid and chenodeoxycholic. Action of bacteria in terminal ileum and colon may dehydroxylate bile acids, yielding the secondary bile acids deoxycholic acid and lithocholic acid. The hepatocytes conjugate most of primary bile acids to small molecules such as glycine and taurine before secreting them into the bile. The liver may also conjugate some primary and secondary bile acids to sulfate or glucuronate