Pathoma - Liver - Fundamentals Of Pathology

Front 1

What is the earliest sign of jaundice?

Back 1

Scleral icterus

Front 2

Jaundice shows up when bilirubin is usually more than _______.

Back 2

2.5 mg/dL

Front 3

After conjugated bilirubin in bile enters the environment of bacteria in the gut, what happens to the molecule?

Back 3

CB is converted into urobilinogen

Front 4

What makes stool brown?

Back 4

Urobilin

Front 5

After urobilinogen has been made in the gut, where does it go?

Back 5

Stool. Some is reabsorbed into the blood and filtered into the kidney making the urine yellow.

Front 6

These are causes of jaundice and involve the marrow, spleen and macrophages. What are they? What happens?

Back 6

(1) Extravascular hemolysis (excessive of RBCs in reticuloendothelial system)
(2) Ineffective erythropoiesis (death of RBCs in marrow)

High levels of UCB overwhelm the conjugating ability of the liver.

Front 7

What color is the urine in extravascular hemolysis and ineffective erythropoiesis? And why?

Back 7

Dark urine.

Large amounts of unconjugated bilirubin gets conjugated and dumped into bile. This means high amounts of urobilinogen that will get reabsorbed, coloring the urine.

Front 8

In extravascular hemolysis or ineffective erythropoiesis there is increased risk for ___________________.

Back 8

pigmented bilirubin gallstones

Front 9

What is physiologic jaundice of the newborn?

Back 9

Newborn liver has transiently low uridine glucuronidyl transferase activity (UGT). This increases unconjugated bilirubin.

Front 10

What is kernicterus?

Back 10

A sequence where unconjugated bilirubin deposits in the basal ganglia of babies, leading to neurological deficits and death. Kernicterus is a concern in a child with high UCB.

Front 11

Treatment of physiologic jaundice of the newborn? How does it work?

Back 11

Phototherapy. Makes UCB water soluble.

Front 12

What is Gilbert syndrome?

Back 12

Due to mildly low UGT activity; AR. Increased UCB during fasting or stress (e.g., infection) otherwise, not clinically significant.

Front 13

What is Crigler-Najjar syndrome?

Back 13

Absence of UGT. Increased UCB with kernicterus. Usually fatal.

("Crigler-Najjar sounds like more of a crook than Gilbert ie more severe")

Front 14

What is Dubin-Johnson syndrome?

Back 14

Deficiency of bilirubin canalicular transport protein; AR. Not clinically significant. Increases CB.

Front 15

A surgeon finds a pitch dark liver in a patient. What is this?

Back 15

Dubin-Johnson syndrome ("Dubious looking liver")

Front 16

What is Rotor syndrome?

Back 16

Same as Dubin Johnson however the liver is not black.

Front 17

Biliary tract obstruction is a cause of jaundice. It is associated with what?

Back 17

(1) Gallstones
(2) Pancreatic carcinoma
(3) Cholangiocarcinoma
(4) Parasites
(5) Liver fluke (clonorchis sinensis)

Front 18

Laboratory findings in obstructive jaundice?

Back 18

Elevated CB, decreased urine urobilinogen, increased alkaline phosphatase.

Front 19

Clinical features of obstructive jaundice?

Back 19

Dark urine (CB) and pale stool. Pruritus due to bile salts in blood. Hypercholesterolemia with xanthomas. Steatorrhea with malabsorption of fat-soluble vitamins (ADEK).

Front 20

What happens in viral hepatitis? Lab findings? Clinical?

Back 20

Inflammation disrupts hepatocytes and small bile ductules. Increase in both CB and UCB. Dark urine due to increased urine bilirubin; urine urobilinogen is normal or decreased.

Front 21

Viral hepatitis is inflammation of _____________.

Back 21

liver parenchyma

Front 22

Viral hepatitis is usually due to?

Back 22

(1) Hepatitis alphabet soup
(2) Other: EBV, CMV

Front 23

Hepatitis virus causes ___________ which may progress to ____________.

Back 23

acute hepatitis; chronic hepatitis

Front 24

Clinical features of acute hepatitis?

Back 24

(1) Jaundice (mixed CB and UCB)
(2) Dark urine (CB)
(3) Fever
(4) Malaise
(5) Nausea
(6) Elevated liver enzymes (ALT more than AST)
(7) Symptoms last less than 6 months

Front 25

What is the mechanism of destruction of hepatocytes in acute viral hepatitis?

Back 25

Apoptosis

Front 26

How is chronic hepatitis defined?

Back 26

(1) Symptoms that last more than 6 months with appropriate serologic markers

Front 27

In chronic hepatitis there is a risk for progression to what?

Back 27

Cirrhosis

Front 28

In chronic inflammation the inflammation predominantly involves what?

Back 28

Front 29

HAV is commonly acquired by __________.

Back 29

travelers

Front 30

HEV is classically acquired from _____________ or ___________.

Back 30

contaminated water; undercooked seafood

Front 31

These hepatitis viruses produce acute hepatitis but with no chronic state.

Back 31

Hepatitis A and E

Front 32

Immunization is only available for hepatitis ______ (A/E) virus.

Back 32

HAV only

Front 33

In the case of HAV or HEV infection, what antibodies marks active infection and what marks protection against recurrent infections?

Back 33

Anti-virus IgM marks active infection, Anti-virus IgG is protective (indicates prior infection or immunization)

Front 34

HEV is associated with fulminant hepatitis in one circumstance. What is it?

Back 34

When a pregnant woman gets infected with HEV she can get liver failure with massive liver necrosis.

Front 35

These viruses are transmitted fecal-orally.

Back 35

Hepatitis A and E virus

(fAEcal transmission)

Front 36

Hepatitis B virus is transmitted ________________.

Back 36

parenterally (IV drug abuse, unprotected intercourse, childbirth.

Front 37

HBV results in acute hepatitis. Chronic disease occurs in _____% of cases.

Back 37

20%

Front 38

What is the key marker of infection with HBV?

Back 38

HBsAg

Front 39

This is the first serologic marker to rise during the acute phase of infection with HBV.

Back 39

HBsAg

Front 40

When does hepatitis B surface antigen disappear?

Back 40

When the patient resolves the infection

Front 41

What defines a chronic hepatitis B state?

Back 41

If HBsAg is present for more than 6 months.

Front 42

The key marker of "acute battle" in hepatitis B infection is what?

Back 42

IgM against the core (for the first 6 months)

("The core is the core of the matter")

Front 43

What is the major antibody our body uses to defeat hepatitis B?

Back 43

IgM (against the core)

Front 44

Describe the window phase. What is it?

Back 44

A phase that appears after the acute phase when IgM has hammered away at the hepatitis B virus for long enough for it to be eradicated.

Now HBsAg is not present and HBeAg is not present. Virus DNA is also absent. The only thing serologically present is IgM.

Front 45

What antibody is produced during the resolved phase of hepatitis B infection?

Back 45

IgG against the core, however, it is not protective.

Front 46

What is the "sign of victory" against hepatitis B?

Back 46

IgG against HBsAg

Front 47

The presence of IgG against HBsAg indicates that ________.

Back 47

YOU HAVE WON THE BATTLE (immunization)

Front 48

What do we give to immunize people against hepatitis B?

Back 48

HBsAg

Front 49

What indicates infectivity in a hepatitis B infection?

Back 49

Envelope antigen (HBeAg)

(E for eeeeeeenfectious)

Front 50

Envelope antigen (HBV) is present during what phases?

Back 50

Acute phase and maybe chronic phase.

Front 51

Transmission of HCV is _________.

Back 51

parenterally (e.g., IVDA, unprotected intercourse, needle stick)

Front 52

What is the risk for acquiring HCV from blood products?

Back 52

Almost nonexistent due to screening of the blood supply.

Front 53

True or false: HCV often progresses to chronic disease.

Back 53

True.

Front 54

What serologic marker will confirm infection with HCV?

Back 54

HCV-RNA

Front 55

During recovery, what serologic markers will go down (HCV)?

Back 55

RNA. Decreasing RNA indicates recovery.

Front 56

Persistence of RNA in HCV indicates what?

Back 56

Chronic disease

Front 57

Hepatitis D is unable to ____________.

Back 57

infect by itself

Front 58

HDV requires _______ for infection.

Back 58

HBV

Front 59

HDV can become superinfected after an HBV infection is established, or it can co-infect with HBV, what is worse?

Back 59

Superinfection

("Super bad")

Front 60

What is cirrhosis?

Back 60

End-stage liver damage characterized by disruption of normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes.

Surface of the liver should be totally smooth.

Front 61

What is the hallmark of cirrhosis?

Back 61

Bands of fibrosis separating regenerating nodules of hepatocytes.

Front 62

What mediates fibrosis in cirrhosis? How?

Back 62

Fibrosis is mediated by TGF-beta from stellate cells.

Front 63

Where are stellate cells located?

Back 63

They lie beneath the endothelial cells that line the sinusoids.

Front 64

One category of findings in the end-stage liver damage in cirrhosis is portal HTN. What clinical findings based on this could you observe?

Back 64

(1) Ascites (fluid in peritoneal cavity)
(2) Congestive splenomegaly/hypersplenism (when it consumes PLTs)
(3) Portosystemic shunts
- Esophageal varices
- Hemorrhoids
- Caput medusae
(4) Hepatorenal syndrome
- Rapidly developing renal failure in the context of cirrhosis.

Front 65

Loss of liver function leads to loss of the ability to ___________ . List some clinical features of this.

Back 65

detoxify

(1) Mental status changes, asterixis, coma
- Due to increased ammonia
(2) Gynecomastia (liver plays important role in removing estrogen from the blood), spider angiomata, palmar erythema
(3) Jaundice

Front 66

Describe manifestations of decreased protein synthesis (which would occur in cirrhosis).

Back 66

(1) Hypoalbuminemia
- Edema
(2) Coagulopathy
- Can't activate vitamin K through epoxide reductase, can't produce coagulation factors

Front 67

In cirrhosis, what would rise, PT or PTT?

Back 67

Both, however the PT is used to follow the degree of deficiency. This is same as for warfarin therapy, which affects epoxide reductase.

Front 68

__________-related liver disease can lead to cirrhosis.

Back 68

Alcohol

Front 69

A man with cirrhosis has a putrid breath. What is the cause?

Back 69

This is fetor hepaticus. Shunting allows thiols from portal blood (from the gut) to go directly to the lungs.

Front 70

What is alcohol-related liver disease?

Back 70

Damage to hepatic parenchyma due to consumption of alcohol.

Front 71

This is the MCC of liver disease in the West.

Back 71

Alcohol

Front 72

Alcohol-related liver disease can present with three patterns of injury, what are they?

Back 72

(1) Fatty liver
(2) Alcoholic hepatitis
(3) Cirrhosis

Front 73

What is fatty liver? What is the result?

Back 73

Accumulation of fat in hepatocytes (due to alcohol). Result is a heavy, greasy liver; resolves with abstinence.

Front 74

What is alcoholic hepatitis? What mediates the damage?

Back 74

Direct chemical injury to hepatocytes; generally seen with binge drinking (fyllefest). Acetylaldehyde mediates the damage.

Front 75

Key finding(s) in alcoholic hepatitis include?

Back 75

(1) Swelling or ballooning of hepatocytes with necrosis and inflammation
(2) Mallory bodies (red encircled)

Front 76

What are mallory bodies?

Back 76

Damaged intermediary filaments within hepatocytes (alcoholic hepatitis)

Front 77

Presentation of alcoholic hepatitis?

Back 77

(1) Painful hepatomegaly and elevated liver enzymes (AST > ALT)
(2) May result in death

("toAST with alcohol")

Front 78

Alcohol damages what intracellular organelle? This leads to a preferential increase in what serum marker?

Back 78

Mitochondria.

AST.

Front 79

Cirrhosis is a complication of _________________________. How many alcoholics get this complication?

Back 79

chronic alcohol-induced liver damage

Seen in about 10-20% of alcoholics.

Front 80

What is Nonalcoholic Fatty Liver Disease?

Back 80

Fatty change, hepatitis and/or cirrhosis. Develops without exposure to alcohol or other known insult.

Front 81

Nonalcoholic fatty liver is associated with?

Back 81

Obesity

Front 82

Nonalcoholic fatty liver disease is a diagnosis of __________.

Back 82

exclusion (you start by making the assumption that the patient is abusing alcohol until proven otherwise)

Front 83

In nonalcoholic fatty liver disease the __________ (AST/ALT) will be greater than the ___________(AST/ALT).

Back 83

ALT > AST (alcohol not involved)

Front 84

What is hemochromatosis? What mediates the damage?

Back 84

Excess body iron that deposits in tissues and damages organs. Damage is mediated by generation of free radicals (fenton rxn).

Front 85

Deposition of iron in tissues is called _____________ (hemosiderosis/hemochromatosis).

Back 85

hemosiderosis. When it causes damage we call it hemochromatosis.

Front 86

Hemochromatosis can be divided into [...]

Back 86

(1) Primary
(2) Secondary

Front 87

What is primary hemochromatosis due to?

Back 87

Mutations in the HFE gene, most commonly a C282Y mutation (All iron that is absorbed enters the blood)

Front 88

Secondary hemochromatosis can arise as a complication of?

Back 88

Transfusions

Front 89

When does hemochromatosis typically present?

Back 89

Late adulthood. Takes time for it to build up.

Front 90

Classic findings in hemochromatosis?

Back 90

(1) Cirrhosis
(2) Secondary diabetes ("Bronze diabetes")
(3) Bronze skin
(4) Cardiac arrhythmia
(5) Gonadal dysfunction (testicular atrophy)

Front 91

Lab findings in hemochromatosis?

Back 91

Based on an iron overloaded state:

(1) Increased ferritin with decreased TIBC
(2) Increased serum iron
(3) High percent saturation

Front 92

When you suspect hemochromatosis you perform a _______.

Back 92

biopsy (usually liver)

Front 93

What do you see on biopsy of a liver affected by hemochromatosis?

Back 93

(1) Brown pigment in hepatocytes

We distinguish it from lipofuscin by staining with Prussian blue which stains iron blue.

Front 94

What is lipofuscin?

Back 94

Wear and tear pigment derived from breakdown of peroxidized lipids. Piles up in the lysosomes. Sign of aging.

"The grey hair of the cells"

Front 95

How could you treat patients with hemochromatosis?

Back 95

Phlebotomy

Front 96

In hemochromatosis there is an increased risk for _______________ in the liver.

Back 96

hepatocellular carcinoma

Front 97

What is Wilson's disease? (brief, leave out pathogenesis)

Back 97

AR defect (ATP7B gene) in ATP-mediated hepatocyte copper transport. Can lead to cirrhosis. Results in lack of copper transport into bile and lack of copper incorporation into ceruloplasmin.

Front 98

Describe the pathogenesis of Wilson's disease.

Back 98

Copper builds up in the hepatocytes, leaks into serum and deposits in tissues. Copper-mediated production of hydroxyl radicals lead to tissue damage.

Front 99

When does Wilson's disease present? How does it present?

Back 99

Childhood.

(1) Cirrhosis
(2) Neurologic manifestations (asterixis; liver flap, behavioral changes, dementia, chorea)
(3) Kayser-Fleischer ring in cornea
(4) Risk for hepatocellular carcinoma

Front 100

A child with parkinson like symptoms (or huntington's disease) what would you think about?

Back 100

Wilson's disease.

Front 101

Treatment of Wilson's disease?

Back 101

D-penicillamine

Front 102

Laboratory findings in Wilson's disease?

Back 102

(1) Increased urinary copper
(2) Decreased serum ceruloplasmin
- We don't have the ability to load ceruloplasmin with copper, so we won't have too much ceruloplasmin floating in the blood.
(3) Increased copper on liver biopsy

Front 103

What is primary biliary cirrhosis? (brief)

Back 103

Autoimmune granulomatous destruction of intrahepatic bile ducts. Etiology unknown, however Anti-mitochondrial antibody is present.

Front 104

Primary biliary cirrhosis classically arises in?

Back 104

Classically arises in women (average age 40)

Front 105

Primary biliary cirrhosis is associated with other _____________.

Back 105

autoimmune diseases

Front 106

How do patients with primary biliary cirrhosis present?

Back 106

With obstructive jaundice.

Cirrhosis is a late complication.

Front 107

What is primary sclerosing cholangitis?

Back 107

Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts.

Front 108

What does primary sclerosing cholangitis result in which you could observe on microscopy?

Back 108

Periductal fibrosis (hence sclerosing) with an 'onion-skin' appearance. Also we could see a 'string-of-pearl'. This is because uninvolved regions of the bile ducts become dilated.

Front 109

What is the etiology of primary sclerosing cholangitis?

Back 109

Etiology is unknown, however a p-ANCA is often positive.

Front 110

Primary sclerosing cholangitis is associated with what?

Back 110

Ulcerative colitis

Front 111

Patients with primary sclerosing cholangitis presents how?

Back 111

With obstructive jaundice.

Cirrhosis is a late complication. There is an increased risk for hepatocellular carcinoma.

Front 112

What is Reye syndrome?

Back 112

Fulminant liver failure and encephalopathy in children with viral illness who take aspirin. Likely related to mitochondrial damage of hepatocytes.

Front 113

How do patients with Reye syndrome present?

Back 113

(1) Hypoglycemia
(2) Markedly elevated liver enzymes
(3) Nausea with vomiting

Can progress to coma and death.

Front 114

What is a hepatic adenoma? What is it associated with?

Back 114

Benign tumor of hepatocytes. Associated with oral contraceptive use and it regresses upon cessation. Also associated with use of testosterone.

Front 115

Complications of a hepatic adenoma?

Back 115

(1) Risk of rupture and intraperitoneal hemorrhage, especially during pregnancy.

Front 116

Why is there a risk of rupture of hepatic adenomas?

Back 116

Because they are sub-capsular.

Front 117

Risk factors for hepatocellular carcinoma?

Back 117

(1) Cirrhosis
(2) Chronic hepatitis
(3) Aflatoxins derived from Aspergillus

Front 118

Aflatoxins induce what in hepatocytes?

Back 118

p53 mutations

Front 119

There is a similarity between hepatocellular carcinoma and renal carcinoma. What is it?

Back 119

They both love to invade veins. Hepatocellular carcinoma often invades the hepatic vein, which can lead to Budd-Chiari syndrome (liver infarction secondary to obstruction of this vein).

Front 120

How does Budd-Chiari syndrome present?

Back 120

Presents with painful hepatomegaly and ascites.

Front 121

Prognosis of hepatocellular carcinoma? Why?

Back 121

Poor, because they are often detected late because symptoms are often masked by cirrhosis.

Front 122

This is a useful serum tumor marker for hepatocellular carcinoma.

Back 122

Alpha-fetoprotein

Front 123

What is more common in the liver, metastasis or primary liver tumors?

Back 123

Metastasis

Front 124

What are the most common sources of metastasis to the liver?

Back 124

(1) Colon carcinoma
(2) Pancreatic carcinoma
(3) Lung & breast

Front 125

What would you see on physical exam of a patient with metastasis to the liver?

Back 125

Metastasis results in multiple nodules in the liver. Clinically this may be detected as hepatomegaly with nodular free edge of the liver (bumps are felt).