Gih Week 2: Liver Pathology Holliman

Front 1

The liver and the gallbladder develop from what embryological structure?

Back 1

Ventral foregut

Front 2

Most of the blood that enters the liver comes from which vessel--the portal V or the Hepatic A?

Back 2

Portal V (75%)
Hepatic A (25%)

Front 3

What are the 4 areas of anastomeses between the portal and systemic venous circulations?1

Back 3

1. Gastric and esophageal VV
2. Para-umbilical VV
3. Hemorrhoidal VV
4. Retroperitoneal VV

Front 4

The hepatocytes surrounding the portal tracts are termed the...

Back 4

Limiting plate

Front 5

What is the least well perfused area of the liver?

Back 5

Centrilobar region (zone 3 of acinus)

Front 6

What is the best perfused area of the liver?

Back 6

Periportal region (zone 1)

Front 7

Describe the flow of bile.

Back 7

(opposite direction to blood flow)

Centrilobar region --> portal tracts --> small bile canaliculi--> intermediate ductules of Hering --> interlobular bile ducts

Front 8

Where is the majority of bilirubin derived from?

Back 8

75% derived from breakdown of RBCs (heme pigment converted to biliverdin, which is then converted to bilirubin)

Front 9

How is bilirubin that is formed outside the liver transported?

Back 9

It is tightly bound to albumin for transport to the liver
(*Cannot be excreted in urine and cannot pass the blood-brain barrier in this form)

Front 10

If the amount of bilirum exceeds capacity of albumin to bind it, what can be the result?

Back 10

Unconjugated (indirect) bilirubin may cross the blood-brain barrer where it tends to localize in the cerebral cortex and basal ganglia causing KERNICTERUS.

Front 11

What is kernicterus and what can be the result?

Back 11

Accumulation of bilirubin in the cerebral cortex and basal ganglia. This occurs when the amount of bilirubin exceeds the carrying capacity of albumin.

*Can result in brain damage, and if severe enough, DEATH.

Front 12

How and where is bilirubin converted from its insoluble form to its soluble form?

Back 12

Bilirubin dissociates from albumin, enters hepatocytes, and is made soluble in the endoplasmic reticulum.

This is accomplished by the enzyme glucuronyl transferase, which conjugates bilirubin to glucoronic acid.

Front 13

How is bilirubin diglucoronide converted to urobilinogen?

Back 13

The diglucoronide is split and the bilirubin is converted by small bowel bacteria to urobilinogen.

Front 14

What form of bilirubin is reabsorbed into portal circulation to return to the liver or reabsorbed into the general circulation to be excreted by the kidneys?

Back 14

Urobilinogen

Front 15

What is partially responsible for the normal brown color of stool?

Back 15

Urobilin.
Urobilinogen left in the stool is converted to Urobilin.

Front 16

How is jaundice produced?

Back 16

Accumulation of bilirubin in the tissues and body fluids
(turns skin and sclera yellow-green color)

Front 17

What are the most frequent causes of jaundice?

Back 17

1. Viral hepatitis
2. Cirrhosis
3. Extra-hepatic biliary obstruction
4. Drug-induced cholestasis

Front 18

List 4 mechanisms of bilirubin accumulation.

Back 18

1. Excess production of bilirubin
2. Reduced hepatic cell uptake
3. Impaired conjugation
4. Impaired excretion of conjugated bilirubin

Front 19

What will be the result of hemolytic anemia (in reference to its effect on bilirubin)?

Back 19

1. Increased levels of unconjugated bilirubin (due to breakdown of RBCs)
2. Mild jaundice

Front 20

What is the major source of intereference in the uptake of unconjugated bilirubin in hepatocytes?

Back 20

Drugs

Front 21

What is the cause of physiologic jaundice of the newborn?

What is the treatment?

Back 21

Immaturity of the hepatic conjugating system

Phototherapy is used to decrease serum bilirubin by breaking down bilirubin into smaller, more polar derivatives that can be excreted in the bile or urine.

Front 22

What might be the cause of breast milk jaundice?

Back 22

The presence of glucoronidases in breast milk. May also be presence of glucoronyl transferase inhibition.

Front 23

What causes Gilbert syndrome?

Back 23

(autosomal dominant disease)
Decreased activity of glucoronyl transferase activity--> impaired conjugation of bilirubin.

Front 24

What syndrome is due a severe defect glucoronyl transferase, resulting in kernicterus?

Back 24

Type I Crigler-Najjar syndrome

Front 25

What is the difference between Type 1 and Type 2 Crigler-Najjar syndrome?

Back 25

Type 1 is far more severe. Bilirubin is NOT conjugated, and results in kernicterus (which is fatal). Autosomal recessive

Type 2 is much less severe. Normal levels of conjugated bilirubin. Not fatal. Similar to Gilbert Syndrome

Front 26

What is cholestasis?

Back 26

Any condition in which the flow of bile is obstructed-->results in interference in the excretion of conjugated bilirubin

Front 27

What type of lab results are consistent with intrahepatic jaundice?

Back 27

1. Increased transaminases
2. Increased LDH
3. Increased prothrombin time

Front 28

Which hereditary disorder results in chronic or recurrent jaundice, mild conjugated bilirubemia, and accumulation of a peculiar dark pigment?

What syndrome is similar to this one, but lacks the hepatic pigmentation?

Back 28

Dubin-Johnson syndrome

Rotor syndrome

Front 29

What is the general cause of extrahepatic jaundice?

Back 29

Narrowing or obstruction of the biliary tract or ampulla of Vater

Front 30

What are the most common causes of extrahepatic jaundice?

Back 30

1. Gallstones lodged in common bile duct
2. Bile duct carcinoma
3. Carcinoma of head of pancreas

(Acute pancreatitis with swelling of head of pancreas can also be a cause)

Front 31

What causes the formation of "bile lakes" in the liver?

Back 31

Rupture of canaliculi produce bile lakes, consisting of dead or dying bile-stained hepatocytes.

(Occurs in obstructive jaundice)

Front 32

What causes pruritis in jaundice?

Back 32

Accumulation of bile acids in the blood

Front 33

What causes xanthelasma in chronic cholestasis?

Back 33

Hypercholesterolemia can result in sharply demarcated, yellowish collections of cholesterol under the skin
(usually begins near inner corner of eye and spreads laterally)

*Later tuberous xanthomas may develop on extensor surfaces, pressure areas, and scars.

Front 34

What are some clinical signs and symptoms of obstructive jaundice?

Back 34

1. Increased conjugated bilirubin in serum
2. Acholic stools
3. Bilirubinuria
4. Decreased absorption of fats
5. Pruritis

Chronic symptoms:
1. Hypercholesterolemia
2. Xanthelasma/ tuberous xanthomas
3. Discoloration of nails
4. Clubbing of digits

Front 35

What sort of lab findings would you expect to find in obstructive jaundice?

Back 35

1. Increased ALP (represent damage to biliary epithelium)
2. Increased transaminases
3. Increased LDH

Front 36

What sort of condition results from drugs that interfere with the excretion of conjugated bilirubin from the hepatocytes?

Back 36

Cholestasis

Front 37

In general, what does the elevation of transaminases indicate?

What does the elevation of alkaline phosphate indicate?

Back 37

transaminases --> hepatocellular damage

ALP --> damage to biliary epithelium

Front 38

In individuals with only cholestasis, what levels of ALP or transaminases would you expect?

Back 38

Elevated ALP
Norman transaminases

Front 39

What is acute congestion of the liver characterized by?

Back 39

Enlarged swollen liver engorged with blood

Front 40

What is the cause of "nutmeg liver"?

Back 40

Chronic congestion
(Congested central portions of the liver lobules become depressed, but stand out against the paler liver tissue)

Front 41

What is the cause of cardiac sclerosis?

Back 41

Chronic congestion
(Long-standing pressure may cause atrophy or necrosis of the liver cells, resulting in fibrosis of the necrotic areas)

Front 42

Occlusion of the hepatic artery is most serious when it occurs where?

Back 42

Distal to its last major extrahepatic branch (gastroduodenal A).

Front 43

What causes a "Zahn's infarct?"

Back 43

Occlusion of a portal vein branch.
(Doesn't lead to a true infarct--demarcated purplish discoloration of the parenchyma, resulting from congestion of sinusoids).

Front 44

What could be some causes of a venous infarction?

Back 44

1. Regional infection
2. Thrombus from portal V
3. Hypercoaguable state
4. External compression

Front 45

How is systemic hypotension reflected in the liver?

Back 45

Necrosis occurs in the poorly oxygenated centrilobar (zone 3) region.

Front 46

Budd-Chiari syndrome results from thrombosis of which veins?

Back 46

Major hepatic veins or IVC

Front 47

List 2 possible causes of Budd-Chiari syndrome.

Back 47

1. Hypercoagulable state
2. Primary carcinoma that extends into hepatic veins

Front 48

What are some symptoms associated with Budd-Chiari syndrome.

Back 48

1. Pain and enlargement of liver (acute occlusion)
2. Ascites
3. Hepatic failure--> DEATH

Front 49

Veno-occlusive disease is occurs most frequently in what patients?

Back 49

Bone marrow transplant patients who have received high doses of radiation and/or chemotherapy

*Toxic damage to small branches of hepatic veins.

Front 50

What could be some clinical signs of portal vein thrombosis?

Back 50

1. Portal hypertension
2. Congestion splenomegaly
3. Ascites

Front 51

In general, what causes portal hypertension?

Back 51

Impaired venous flow through portal system.

Front 52

List some specific conditions that can lead to portal hypertension.

Back 52

1. **Laennec's cirrhosis
2. Budd-Chiari syndrom
3. Veno-occlusive disease
4. Portal vein compression/thrombosis

Front 53

How do the intrahepatic shunts between the hepatic artery and portal vein contribute to increased portal pressure?

Back 53

In cirrhosis, these intrahepatic shunts are enlarged, resulting in increased portal pressure

Front 54

What are the major symptomatic consequences of portal hypertension?

Back 54

1. Ascites
2. Splenomegaly
3. Collateral venous channels

Front 55

Which damaged anastomoses results in esophageal varices?

Back 55

Gastroesophageal plexus

Front 56

Which collateral venous plexus connects the superior mesenteric V of the portal system with the inferior mesenteric system?

Back 56

Hemorrhoidal plexus

Front 57

What is the principal cause of death in about half of patients with cirrhosis?

Back 57

Bleeding from ruptured esophageal varices

Front 58

What condition may develop in patients whose fetal umbilical vein has not become totally obliterated?

Back 58

Caput medusa

Front 59

Does engorgement of retroperitoneal collateral channels generally produce signs or symptoms or hemorrhages?

Back 59

No.

Front 60

What are some clinical signs of congestive splenomegaly?

Back 60

Hypersplenism may develop which can cause:
1. Anemia
2. Leukopenia
3. Thrombocytopenia

*Can lead to Hemorrhagic diathesis (unusual susceptibility to bleeding)

Front 61

Intraperitoneal accumulation of watery fluid.

Back 61

Ascites

Front 62

Describe the role of renin activity in ascites.

Back 62

Decreased blood flow to kidney results in increased renin activity, which results in an increased retention of Na+ and H2O.

Front 63

What type of cells might be present in ascitic fluid?

Back 63

Mesothelial cells and a few lymphocytes = normal

(RBCs and neutrophils should NOT be present)

Front 64

If RBCs are found in ascitic fluid, what could this indicate?

Back 64

Possible involvement of peritoneal surfaces by malignancies

Front 65

What does the presence of large numbers of neutrophils in ascitic fluid indicate?

Back 65

Peritoneal irritation, most likely peritonitis

Front 66

What condition is characterized by purulent bacteria in intrahepatic bile ducts?

Back 66

Cholangitis

Front 67

How does cholangitis generally begin?

Back 67

Extrahepatic biliary obstruction--usually common bile duct obstructed by gallstones
(or carcinoma of head of pancreas)

Front 68

What are some clinical symptoms of cholangitis?

Back 68

1. High fever
2. Enlarged liver

Front 69

What is the incubation period for HAV?

Back 69

2-6 weeks
*Period of peak infectivity since the virus is shed in the feces during this time.

Front 70

By the time symptoms appear in Hepatitis A, is the virus still being shed?

Back 70

No

Front 71

Which hepatitis virus consists of a "Dane particle?"

Back 71

Hepatitis B
(double shelled particle)

Front 72

What portion of the hepatitis B virus is probably the infections agent?

How is this virus primarily transmitted?

Back 72

Dane particle

Parental transmission--blood products or needle-contamination

Front 73

What is the incubation period for Hepatitis B?

Back 73

6 weeks - 6 months

Front 74

What are the 3 major antigens associated with HBV?

Which ones are associated with the core?

Back 74

HBsAg
HBcAg <---core
HBeAg <---core

Front 75

Today, most HCV infections are associated with what type of transmission?

Back 75

Risky behavior:
1. IV drug use
2. Multiple sex partners
3. Needlestick injury

Front 76

Is a patient more likely to develop a chronic disease with HBV or HCV?

Back 76

HCV

Front 77

In what circumstance is an HDV infection likely to induce chronic progressive hepatic damage-- in patients with active HBV infection or in HBV carriers?

Back 77

HDV infection of HBV carriers is likely to induce chronic progressive hepatic damage

HDV coinfection in patients with an active HBV infection will rarely progress to chronic disease.

Front 78

What is the incubation period of HEV?

Back 78

2-9 weeks

Front 79

What type of individuals are at a greater risk of developing fulminant hepatitis from an HEV infection?

Back 79

Pregnant women

Front 80

Which hepatitis virus appears to be non-pathogenic, and may be seen as a co-infection of Hepatitis C?

Back 80

Hepatitis G

Front 81

What is anicteric hepatitis?

Back 81

Hepatitis without the development of increased bilirubin levels, therefore no jaundice appears.

Front 82

How is Chronic hepatitis defined?

Back 82

Any hepatitis which persists for more than six months

Front 83

What is the most common form of cirrhosis?

Back 83

Laennec's (alcoholic) cirrhosis

Front 84

What type of cirrhosis is frequently associated with hepatocellular carcinoma?

Back 84

Postnecrotic cirrhosis
(following episode of viral infection or drug/chemical toxicity)

Front 85

How is copper normally transported in the body after absorption?

Back 85

It normally complexes with ceruloplasmin

Front 86

How is copper transported in patients with Wilson's disease?

Where is the copper deposited?

Back 86

Since there are low levels of ceruloplasmin, the copper in transported by complexing to albumin.

Copper deposits in the liver, brain, kidneys, and cornea

Front 87

Which condition is most common in young children, and consists of fatty liver development associated with encephalopathy? Also associated with the ingestion of Aspirin.

Back 87

Reye's syndrome

Front 88

What are 2 frequent causes of hepatic failure?

Back 88

1. Viral hepatitis
2. Cirrhosis

Front 89

What symptom is not indicative of liver failure, but is almost always present when failure occurs?

Back 89

Jaundice