EXAM #2: LIVER PATHOLOGY Flashcards Preview

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Flashcards in EXAM #2: LIVER PATHOLOGY Deck (73):
1

What are the four most common causes of chronic liver disease in US? (List in order of prevalence)

1) Hepatitis C
2) Alcoholic liver disease
3) Non-alcoholic fatty liver disease
4) Hepatitis B

2

What is meant by hepatocyte integrity?

Membrane integrity of hepatocytes

****When damaged, hepatocytes are "leaky"****

3

What are the two classic liver lab tests?

AST
ALT

*****Finding these enzymes in the serum indicates that there has been damage to the hepatocytes that have made them "leaky"*****

4

What three lab tests test hepatocyte function? What happens to these tests with impaired liver function?

1) Serum albumin--decreased
2) Prothrombin time--increased
3) Serum ammonia--increased

5

What lab tests are associated with obstructed bile flow?

1) ALP
2) 5'-Nucleotidase (5'-NT)
3) GGT

6

What are the two types of bilirubin? What is the difference between direct and indirect bilirubin?

- Conjugated= Direct, has sugar moieties added and can be excreted
- Unconjugated= Indirect, no sugar moieties

*****Unconjugated is "indirect" b/c it is an indirect measurement (Total- conjugated= unconjugated)*****

7

What is the normal serum total bilirubin level?

0.1-1.2 mg/dL

8

What are the clinical manifestations of hyperbilirubinemia?

- Jaundice
- Cholestasis= slowing of the flow of bile

9

How high does the serum bilirubin need to be for there to be clinical symptoms?

Carvenale= greater than 2 mg/dL

Pathoma= greater than 2.5 mg/dL

10

Outline normal bilirubin metabolism.

1) RBCs are consumed by splenic macrophages
2) Protoporphyrin (from heme) is converted into UNCONJUGATED bilirubin (UCB)
- Heme oxygenase= Biliverdin
- Biliverdin reductase= Unconjugated Bilirubin
3) UCB binds albumin and is carried to the liver
4) In the hepatocyte ER, UCB is CONJUGATED to CB, via Uridine Glucuronyl Transferase (UGT)
5) CB is transferred to bili canaliculi via MDR-2 and MDR-3 transporters to form bile
6) Bile is stored in the gallbladder
7) Bile is released into the duodenum
8) Intestinal flora convert CB to UROBILINOGEN in the bowel
9) Urobilinogen is oxidized to STERCOBILIN and UROBILIN

11

What enzyme conjugates UCB in the hepatocyte?

UGT, Uridine Glucuronyl Transferase
- Adds one sugar to bilirubin i.e. monoglucuronides
- OR adds 2x sugars to make diglucuronides

(UGT1A1)

12

What heme degradation product gives stool its color?

Sterocobilin

13

What heme degradation product gives urine its color?

Urobilin

14

What is the etiology of hyperbilirubinemia seen in extravascular hemolysis or ineffective erythropoiesis?

- Increased UCB b/c of heme degradation
- UCB overwhelms liver's ability to conjugate

15

What is the lab finding in extravascular hemolysis/ ineffective erythropoiesis?

Elevated UCB

16

What are the clinical features of extravascular hemolysis/ ineffective erythropoiesis?

1) Dark urine due to increased urine UROBILINOGEN
2) Increased risk for pigmented bilirubin gallstones (excess UCB must eventually be converted to CB--hyperaccumulation of which can cause gallstones)

****Note that UCB is NOT water soluble and will NOT be in urine****

17

What is the etiology of physiologic jaundice of the newborn?

Newborns have transiently low UGT (UCB-->CB)

18

What is the lab manifestation in physiologic jaundice of the newborn?

Elevated UCB

19

What is the clinical manifestation of physiologic jaundice in the newborn?

Possible kernicterus
- UCB is fat soluble
- Deposits in the basal ganglia and causes neurologic deficits/death

20

How is physiologic jaundice of the newborn treated?

Phototherapy, which makes UCB more water souble

****Note that phototherapy does NOT conjugate UCB*****

21

What is the etiology of Gilbert Syndrome?

Mildly low UGT activity due to a promoter mutation

22

What is the inheritance pattern of Gilbert Syndrome?

Autosomal recessive

23

What lab finding is associated with Gilbert Syndrome?

Elevated UCB

24

What are the clinical features associated with Gilbert Syndrome?

1) Predominantly asymptomatic
2) STRESS e.g. severe infection causes hyperbilirubinemia

25

What is the etiology of Crigler-Najjar Syndrome Type I?

Autosomal recessive absence of UGT

26

What is the lab finding in Crigler-Najjar Syndrome?

Extremely elevated UCB

27

What are the clinical manifestations of Crigler-Najjar Syndrome?

Kernicterius that is typically fatal

28

How does Crigler-Najjar Syndrome Type 2 differ from Type 1?

Type 2=
- AUTOSOMAL DOMINANT with variable penetrance
- Moderate decrease in UGT activity
- Only occasional kernicterus

****NOTE that this is TREATED WITH PHENOBARBITAL*****

29

What is the etiology of Dubin-Johnson Syndrome?

Autosomal recessive mutation in MDR-2 transporter that impairs CB transfer to bile canaliculi

30

What lab finding is associated with Dubin-Johnson Syndrome?

Elevated CB

31

What are the clinical manifestations of Dubin-Johnson Syndrome?

Dark liver otherwise innocuous

32

What is Rotor Syndrome?

Autosomal recessive disorder similar to Dubin-Johnson Syndrome, but NO BLACK LIVER

33

How do you tell the difference between Dubin Johnson Syndrome and Rotor Sydrome?

1) +/- black liver
2) Labs

34

What labs are characteristic of Dubin-Johnson's Sydrome?

- Normal urine coproprophyrins (heme proteins)
- Increased isomer I

35

What labs are characteristic for Rotor Syndrome?

- Increased urine coproprophyrins
- Normal isomer I

36

What is the etiology of Progressive Familial Intrahepatic Cholestasis (PFIC)?

- Defects in various biliary epithelial transports (transporters that secrete bile components into bile canaliculi)
- Causes cholestasis and failure to thrive

37

What are the normal components of bile?

1) Bile salts that emulsify fat
2) Cholesterol
3) Lecithin
4) Bilirubin
5) Bicarbonate

38

What is the specific mutation in PFIC-1?

Defect in the canalicular ATPase
- Cannot shunt bile into canaliculi without ATP

39

What is the specific mutation in PFIC-2?

Defect in a Bile Salt Export Pump

40

What is the specific mutation seen in PFIC-3?

Defect in MDR-3 and impairs phosphatidylcholine transport

41

What is the inheritance pattern for the PFICs?

Autosomal recessive

42

What are the clinical manifestations of the PFICs?

1) Cholestasis (has a toxic effect on the liver and can cause fibrosis/cirrhosis)
2) Fat malabsorption
3) Fat soluble vitamin deficiency
4) Osteopenia
5) Liver failure

*****Note that symptoms begin in infancy and progress to cirrhosis within the first decade of life*****

43

What are the two most common bile duct obstructions?

1) Gallstones
2) Pancreatic carcinoma

44

What are the clinical manifestations of bile tract obstruction i.e. obstructive jaundice?

1) Jaundice
2) Steatorrhea w/ malabsorption (no bile for fat emulsification)
3) Dark urine due to BILIRUBINURIA
4) Xanthomas from hypercholesterolemia
5) Pruritis due to increased plasma bile acids
6) Osteoporosis (not absorbing Vitamin D)
7) Bleeding--impaired Vitamin K production

45

What are the lab findings biliary tract obstruction?

1) Elevated CB
2) Decreased urine urobilinogen
3) Elevated
- ALP
- GGT
- 5-NT
4) Hyperlipidemia

46

What are the most common causes of cirrhosis?

1) Alcoholic liver disease
2) Viral hepatitis
3) Obesity

47

Outline the pathogenic progression of cirrhosis. What are the hallmarks of cirrhosis?

- Hepatocyte necrosis leads to:
1) Progressive fibrosis
2) Regenerative hepatocyte nodules

*****Bands of fibrosis and regenerative nodules are the hallmarks for cirrhosis*****

48

What is the mechanism of liver fibrosis?

1) Kupffer Cells secrete factors that cause stellate cells to convert to myofibroblasts
2) Stellate cells/ myofibroblasts secrete TGF-B
3) TGF-B causes fibrosis

49

What is the definition of micronodular cirrhosis? What type of cirrhosis is this associated with?

Cirrhosis with regenerative nodules less than 3mm

*Alcoholic*

50

What is the definition of macronodular cirrhosis? What is macronodular cirrhosis associated with?

Cirrhosis with regenerative nodules greater than 3mm
- Viral hepatitis
- Alpha-1 antitrypsin disease
- Wilson's Disease

51

What are the four manifestations of decompensated cirrhosis?

1) Portal HTN
2) Hepatorenal Syndrome
3) Liver Failure
4) Hepatic Encephalopathy

52

What are the clinical manifestations of portal hypertension?

1) Ascites
2) Congestive splenomegaly/hypersplenism (consumption of RBCs and platelets)
3) Porotsystemic shunts
- Gastro-esophageal varices
- Rectal varices
- Caput medusae
- Ascites
- Hypersplenism

53

What are the clinical manifestations that result from decreased detoxification in cirrhosis?

1) Hyperammonemia causing:
- Mental status change
- Asterixis
- Coma
2) Reduced liver removal of estrogen/hyperestrinism causing:
- Gynecomastia
- Spider angiomata
- Palmar erythema
- Testicular atrophy
3) Jaundice

54

What does decreased protein synthesis in cirrhosis lead to?

1) Hypoalbuminemia and edema
2) Coagulopathy b/c of
- Decreased synthesis of clotting factors
- Impaired activation of epoxide reductase (Vitamin K)

55

What is ascites?

Excess fluid in the peritoneal cavity

56

What causes ascites?

1) Portal hypertension i.e. liver disease
2) Non-portal hypertension
- TB
- Pancreatitis
- Nephrotic Syndrome

57

What does SAAG stand for?

Serum-ascites albumin gradient

58

What does the SAAG help you differentiate?

Portal HTN= SAAG greater than 1.1 g/dL

Non-portal HTN= less than 1.1 g/dL

59

How much liver function must be lost for a patient to have clinical manifestations of liver failure?

Greater than 80%

60

What are the major clinical manifestations of hepatic failure?

1) Encephalopathy
2) Coagulopathy
3) Jaundice
4) Multiple organ failure

61

What is the definition of hyperacute liver failure?

Failure occurs within 7 days of first symptoms of liver dysfunction (jaundice)

62

What is the definition of acute liver failure?

Failure occurs within 4 weeks of first symptoms of liver dysfunction

63

What is the definition of subacute liver failure?

Failure occurs within 5-12 weeks of first symptoms of liver dysfunction

64

What is the definition of chronic liver failure?

Liver failure in the context of decompensated cirrhosis

65

What is Hepatorenal Syndrome?

Renal failure that occurs in the setting of cirrhosis or fulminant liver failure

66

What causes renal failure in Hepatorenal Syndrome?

Alteration in blood flow/ tone to the kidney in the face of liver failure
- Vasodilation in periphery
- Vasoconstriction to the kidney

67

What are the manifestations of Hepatorenal Syndrome?

1) Oliguria/anuria
2) Increased BUN/ Creatinine
3) Low urinary Na+
4) Normal urinary sediment

68

What is the difference between Type I and Type II Hepatorenal Syndrome?

Type 1= rapidly progressive

Type 2= moderate progression

****Strict definitions are based on serum creatinine*****

69

What is Hepatopulmonary Syndrome?

Triad of:
1) Chronic liver disease
2) Hypoexmia
3) Intra-pulmonary vascular dilation

****This results in V/Q mismatch--less diffusion of oxygen as blood is shunted rapidly through dilated pulmonary vessels****

70

What mediates Hepatopulmonary Syndrome?

Nitric Oxide

71

What is Hepatic Encephalopathy?

Hyperammonemia that results in
1) cerebral edema
2) changes in mental status

****Mercaptans are also part of the pathophysiology, but their role is poorly understood*****

72

What are the clinical manifestations of Hepatic Encephalopathy?

1) Mental status changes
2) Asterixis (flapping tremor)
3) Coma

73

What is fulminant Hepatic Failure?

Acute liver failure with massive liver necrosis leading to:
- Hepatic encephalopathy
- Increased PT/INR