GI Mod 2B

Question 1

6 Functions of the Liver

Answer 1

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

Question 2

Glisson Capsule

Answer 2

1. Surrounds liver contains BV, nerves, lymphatics

Question 3

Bile canaliculi

Answer 3

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)

Question 4

Lobule

Answer 4

= functional unit of liver

1. 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

Question 5

Various immune/defense cells line the sinusoid

Answer 5

Kupffer Cells
Stellate Cells
Pit Cells
Disse Space

Question 6

Kupffer Cells

Answer 6

• Macrophage (phagocytic) cells that line the sinusoids
• Function:
(i) phagocytic cells – RBC breakdown (bilirubin production)
• Clinical:
(i) Early response to liver injury/pathology

Question 7

Stellate Cells

Answer 7

• 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

Question 8

Pit Cells

Answer 8

• Produce interferon and other immune defense substances
• Function:
(i) “first line of defense” against tumor formation
(ii) cytoctoxic effect on tumor cells

Question 9

Disse Space

Answer 9

• The interstitial space between hepatocytes and sinusoids that drains into lymphatic vessels

Question 10

Bile

Answer 10

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

Question 11

What is Bile?

Answer 11

1. Alkaline, yellow fluid that is made of mostly water and electrolytes
2. 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

Question 12

Bile secretion: hepatoenteric pathway

Answer 12

1. Bile secreted into canaliculi
2. Canaliculi eventually drain into R/L hepatic duct and the common hepatic duct
3. 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
4. During feeding
   a. Gall bladder contracts via CCK and vagal stimuli
   • CCK and vagal will also relax sphincter of Oddi to allow flow

Question 13

F. Bile formation and utilization in Liver Circulation

Answer 13

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

Question 14

Bile formation and utilization in Duodenum Circulation

Answer 14

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

Question 15

3. Terminal ileum/colon

Answer 15

a. 90% are absorbed and transported back to the liver

b. 10 % continue to the rectum and are excreted

Question 16

Bilirubin pathway

Answer 16

A. Bilirubin is byproduct of RBC breakdown that needs to be excreted
1. RBC lifespan approximately 120 days

Question 17

Bilirubin pathway– RBC

Answer 17

1. RBCs breakdown in spleen, liver (Kupffer cells) and throughout vascular system
2. 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

Question 18

Bilirubin pathway– Unconjugated bilirubin formation in plasma

Answer 18

1. In the plasma bilirubin attaches to albumin and is unconjugated bilirubin (fat soluble)
2. The unconjugated bilirubin travels to the liver
   a. NOTE: The unconjugated form (fat soluble) can’t be excreted from the kidney

Question 19

Bilirubin pathway– Unconjugated bilirubin is conjugated in the liver

Answer 19

1. the unconjugated bilirubin circulates through the hepatocytes and is conjugated
   a. The conjugated bilirubin is water soluble which allows it to be excreted
2. the newly formed conjugated bilirubin mixes with bile in canaliculi and is secreted into duodenum or stored in gallbladder

Question 20

Intestines (formation of urobilinogen)

Answer 20

1. Conjugated bilirubin secreted into duodenum
2. Bacteria in the intestines “deconjugate” the bilirubin into urobilinogen
3. 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)

Question 21

Urobilinogen in urine

Answer 21

a. Normal values: 0-4 mg/24 hrs
b. Increased values: pre-hepatic jaundice
c. “Decreased” values: post-hepatic jaundice

Question 22

Mechanical pathways of jaundice (hyperbilirubinemia)

Answer 22

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

Question 23

Classification of Jaundice

Answer 23

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

Question 24

Lab Profiles of Jaundice

Answer 24

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)

Question 25

Lab Assessments for Jaundice

Answer 25

• Serum bilirubin
(i) Both the amount and the type of hyperbilirubinemia provide clues to jaundice classification
1. Total bilirubin – measured directly in blood
a. If elevated, consistent with pre-hepatic, intra-hepatic or post-hepatic pathology
2. Direct (conjugated) bilirubin – measured directly in blood
a. If elevated, post-hepatic or intra-hepatic pathology that impairs conjugated bilirubin secretion into GI tract
3. Indirect (unconjugated) bilirubin – calculated from total and direct measurements
a. If elevated, pre-hepatic or intra-hepatic pathology that impairs “conversion” of unconjugated bilirubin to conjugated bilirubin.
(ii) Clinical reality: “indirect vs direct”
1. not necessarily a clear cut presentation…both elevated with one dominating
• Serum enzymes: alkaline Phospatase, AST, ALT, LDH, GGT, etc..
• Serum proteins: albumin, globulins, A/G ratio, transferrin, AFP (alpha fetoprotein), etc…
• Other measures:
(i) stool/urine color
(ii) urinalysis: urobilinogen & conjuugated bilirubin

Question 26

Lab ”patterns” associated with Pre-hepatic pathology

Answer 26

(i) Hemolysis of RBCs increases production of unconjugated bilirubin
(ii) Examples of causes:
1. Genetic disorders, transfusions/reactions, sepsis, burns, etc…
(iii) Lab:
1. Blood: (hyperbilirubinemia)
a. Total bilirubin: elevated
b. Direct (conjugated): normal/potential elevated
i. Possible elevated conjugated bilirubin due to increased production
c. Indirect (unconjugated): elevated
2. Urine: elevated urobilinogen
3. Urine color: normal
4. Stool color: normal

Question 27

Lab ”patterns” associated with Intra-hepatic pathology

Answer 27

(i) Decreased uptake or conjugation in the liver
(ii) Examples:
1. Decreased uptake
a. CHF, drug/medication inhibition
2. Decreased conjugation
a. neonatal (physiological), liver Dz (hepatitis, cirrhosis), hyperthyroidism
(iii) Lab:
1. Blood: (hyperbilirubinemia)
a. Total bilirubin: elevated
b. Direct (conjugated): normal elevated (if obstructive damage to liver)
c. Indirect (unconjugated): elevated
i. Elevated unconjugated bilirubin compared to values of conjugated bilirubin
ii. “congestive’ back up of indirect (unconjugated) bilirubin in bloodstream
2. Urine:
a. low or normal urobilinogen (due to decreased secretion of conjugated bilirubin into intestine)
3. Urine color: normal

Question 28

Lab ”patterns” associated with Post-hepatic pathology

Answer 28

(i) Decreased secretion or transport of conjugated bilirubin from liver
1. Can occur anywhere from within canaliculi to sphincter of Oddi
(ii) Examples”
1. Impairing secretion from hepatocytes: pregnancy, cancer, hepatitis, cirrhosis, infiltrative diseases (amyloidosis, sarcoidosis, TB), meds Impairing secretion in biliary duct system: gallstones stones, strictures, pancreatitis (acute/chronic), cancer/tumors impairing biliary pathway
(iii) Lab:
1. Blood: (hyperbilirubinemia)
a. Total bilirubin: elevated
b. Direct (conjugated): elevated
i. Elevated conjugated bilirubin due to “congestive back-up”
c. Indirect (unconjugated): normal
2. Urine: “elevated conjugated bilirubin makes urine dark”
a. “decreased” urobilinogen
b. elevated conjugated bilirubin (bilirubinuria)
i. bilirubin not normally found in urine
3. Urine color: dark
a. Due to elevated blood values of conjugated bilirubin that are excreted in kidney
4. Stool color: pale
a. Loss of dark color due “decrease” of urobilinogen in