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Flashcards in Nelson: Liver Deck (101):
1

What is jaundice?

Yellow discoloration of the SKIN d/t retention of bilirubin

2

When is jaundice clinically evident?

as total serum bilirubin approaches 2-3 mg/dl

3

What is icterus?

yellow discoloration of the SCLERA d/t retention of bilirubin

4

What is cholestasis?

impaired secretion of BILE

5

What are the steps involved in bilirubin metabolism?

Reticuloendothelial cells convert heme (brkdown of old RBC, hepatic heme, marrow RBC precursors) to bilirubin>
bilirubin is transported to the liver complexed w/ ALBUMIN (unconjugated bilirubin)>
cbilirubin is conjugated w/ glucuronic acid in liver cells (conjugated bilirubin)>
conjugated bilirubin is excreted in BILE (brown stools)

6

What form of bilirubin is toxic to tissues?

Unconjugated (indirect)
-water soluble
-bound to albumin
-not excreted in the urine

7

Which form of bilirubin is water soluble, not toxic to tissues and is excreted in the urine when present at high serum levels?

conjugated bilirubin

8

What are some of the causes of unconjugated bilirubinemia?

1. Increased bilirubin production
2. impaired hepatic bilirubin uptake
3. impaired bilirubin conjugation

9

What increases bilirubin production?

• Extravascular hemolysis
• Extravastation of blood into tissues
• Intravascular hemolysis
• Dyserythropoiesis

10

What impairs hepatic bilirubin uptake?

• Heart failure
• Portosystemic shunts
• Gilbert’s syndrome
• Drugs

11

What impairs bilirubin conjugation?

• Crigler-Najjar syndrome (I or II)
• Gilbert’s syndrome
• Neonatal jaundice
• Hyperthyroidism
• Ethyinyl estradiol
• Liver disease

12

What causes conjugated hyperbilirubinemia?

1. extrahepatic cholestasis (biliary obstruction)

2. interhepatic cholestasis

13

What causes biliary obstruction?

• Choledocholithiasis
• Tumors
• PSC
• AIDS
• Pancreatitis
• Strictures
• Parasitic infxns

14

What causes intrahepatic cholestasis?

• Hepatitis (many types)
• Drugs & toxins
• Primary biliary cirrhosis
• Sepsis & hypoperfusion
• Infiltrative diseases
• Total parenteral nutrition
• Following organ transplant
• Hepatic crisis in sickle cell
• Pregnancy
• End-stage liver disease

15

What causes normal neonatal alterations in bilirubin metabolism?

1. Increased bilirubin production (neonates have relatively more RBCs with a shorter life span)
2. Decreased bilirubin clearance (due to physiologic decrease in UGT1A1 activity)
3. Increased enterohepatic circulation*

16

What are pathological causes of unconjugated hyperbilirubinemia?

• Immune-mediated hemolysis (ABO or Rh(D) incompatibility)
• Inherited RBC membrane or enzyme defect
• Sepsis
• Inherited defects in UGT1A1 activity (e.g. Crigler-Najjar syndrome, Gilbert's syndrome)
• Breast milk jaundice*
• Intestinal obstruction*
• Breastfeeding failure jaundice*

17

What are normal TB levels in almost all term and near term newborn inftants?

>1 mg

18

If an infant has mild unconjugated hyperbilirubinemia w/ peak TB what can you expect the levels to be?

— 7 to 9 mg/dl in Caucasian & AA infants

— 10 to 14 mg/dl in Asian infanats

19

A TB >25-30 mg/dl in an infant is indicative of....

How do you treat it?

severe hyperbilirubinemia

Phototherapy

20

How does severe hyperbilirubinemia affect other organ systems?

1. Bilirubin-induced neurologic dysfunction (BIND)
2. Acute bilirubin encephalopathy (ABE)
3. Long-term neurologic sequelae or kernicterus (if inadequately tx)

21

What is Gilbert's syndrome?

AR, BENIGN disorder

22

What causes Gilbert's syndrome?

decreased GTF activity (UGT1A1 is 30% of normal)

23

What lab findings are associated w/ gilbert's sndrome?

increased unconjugated bilirubin

24

Morphological findings show:
bile w/in hepatocytes
canalicular bile stasis
feathery degeneration of hepatocytes

intrahepatic cholestasis

25

Morphological findings show:
Canalicular bile stasis
Feathery degeneration of hepatocytes
Bile lakes
Bile w/in distended bile ducts
PORTAL TRACT EDEMA
Bile duct proliferation w/in portal tracts

Extrahepatic cholestasis

26

What is acute cholangitis? What is seen morphologically?

secondary bacterial infection of the biliary tree

Extrahepatic biliary obstruction → ascending cholangitis

27

What is chronic passive congestion?

centrilobular congestion

28

WHat is centrilobular hemorrhagic necrosis?

centrilobular congestion w/ cenrilobular necrosis

29

What is cardiac sclerosis?

fibrosing rxn following long standing CPC and or centrilobular necrosis

Pathology--centrilobular fibrosis

30

What are the common causes of CPC, CHN and CS?

RHF, LHF, shock, hepatic vein thrombosis>

congestion and hypoperfusion> centrilobular necrosis

31

What is a hepatic infarct?

rare
secondary to double blood supply

32

What is a hepatic infarct often caused by?

vasculitis, embolism, or tumor

33

What is hepatic vein thrombosis (bud chiari syndrome)?

thrombosis of 2+ hepatic vein branches

34

What is the classical clinical triad for HVT?

hepatomegaly
ascites
abd pain

35

What often causes HVT?

conditions htat make clotting more likely

May also have a thrombosis in the IVC

36

How do you dx HVT?

imaging of thrombi

37

What si the pathology of HVT?

centrilobular hemorrhagic necrosis
cardiac sclerosis

38

What is sinusoidal obstruction syndrome?

presence of obstructive, non-thrombotic lesions of small hepatic veins in pts exposed to radiation &/or hepatoxins

39

What is the pathogenesis of sinusoidal obstruction syndrome?

toxic damage to hepatic sinusoidal endothelium, secondary to cytoreductive agents (e.g. chemotherapy)> MARKED NARROWING/OBLITERATION OF CENTRAL VEIN lumens by SUBENDOTHELIAL SWELLING AND FIBROSIS

40

What is the acute form of sinusoidal obstruction syndrome associated with?

painful hepatomegaly
sudden wt gain
increased serum bilirubin

41

What is the chronic form of sinusoidal obstruction syndrome associated with?

Toxic effects of pyrrolizidine alkaloids found in certain herbal teas

sx of budd chiari

42

How do you dx sinusoidal obstruction syndrome?

clinical features
imaging
liver biopsy (chronic form)

43

What complications are associated wtih portal vein thrombosis?

portal HTN (no ascites b/c obstruction is presinusoidal)

44

What are extrahepatic causes of portal htn?

1. Intraabdominal sepsis
2. hypercoaguable disorders
3. trauma
4. pancreatitis or pancreatic cancer

45

What are intrahepatic causes of PVT?

1. cirrhosis
2. invasion of portal vein by hepatocellular carcinoma

46

What is Peliosis Hepatis?

primary hepatic sinusoidal dilation w/ sinusoidal rupture> blood filled spaces

typically resolves after correction of underlying disorder

47

How is hepatitis A transmitted?

Fecal- oral (contaminated food & water)

48

How does Hepatits A cause infection?

Incubates 2-6 wks>
Virus infects liver cells → hepatocellular injury d/t CD8+ T-cell & lysis of infected hepatocytes

49

How does HAV usually present?

majority are asymptomatic
some present w/ acute hepatitis

does NOT cause chronic hepatitis

50

How is HBV transmitted?

Parenteral, Sexual/close contact, perinatal

Blood & body fluids (saliva, semen, vaginal secretions)

51

How does HBV cause infection?

Incubation period = 4-26 wks
Virus infects liver cells → hepatocellular injury d/t CD8+ T-cell & lysis of infected hepatocytes

52

What percent of HBV pts are asymptomatic? acute? chronic?

Majority (70%) of pts asymptomatic
Some (30%) clinical acute hepatitis
90% of infections resolve

5% develop chronic hepatitis
(1)→ Non-progressive disease
(2)→ Progressive disease→ cirrhosis
(3)→ Hepatocellular carcinoma
(4)→ Asymptomatic carrier state (esp. if exposed as young

53

How is HCV transmitted?

Parenterally (blood, IV drug use), Sexual/close contact, rarely perinatally

54

What percent of pts develop chronic HCV?

20% develop acute hepatitis
80% develop chronic hepatitis
• 20-30% → cirrhosis
• Most pts asymptomatic

55

What is the MCC of chronic liver disease in the US?

HCV
Genotype 1a

56

How is HDV transmitted?

Individual w/ chronic HBV (superinfection)

Transmitted simultaneously w/ HBV (coinfection)

57

What does HVC need in order to replicate?

Only able to replicate in presence of HBV, encapsulated by HBsAg


58

How does an infection w/ HBV and HDV compare to one w/ HBV alone?

MORE SEVERE
• Increased mortality from acute hepatitis
• Increased progression to chronic hepatitis (superinfection form only)

59

What populations is HDV commonly found in?

See in IV drug users or certain geographical locations (Brazil, Africa, Middle East, S. Italy)

60

Can you distinguish and acute coinfection of HBV and HDV from HBV?

No

transiet & self-limited, increased severity, increased risk of liver failure, rate of progression to chronic no different

61

What can an HDV superinfection cause?

• Convert mild chronic HBV hepatitis →acute liver failure (7-10%)
• Cause acute hepatitis to erupt in a healthy, inactive HBV carrier
• → chronic hepatitis (80%, compared to 4% with HBV alone)
• Carrier state also exists

62

How is HEV transmitted?

Fecal oral

63

What population can HEV cause mortality in?

Generally self-limited, but can cause mortality in pregnant women
Does NOT cause chronic hepatitis or carrier state
Very prevalent in underdeveloped countries
Very rare in US

64

We have vaccines for all forms of hepatitis except?

HCV

HEV does have a vaccine but is not available commercially

65

What serological tests are used for HAV?

Infected pts develop Ab response
• IgM HAV preceeds IgG HAV
• IgG persists & provides protective immunity

66

How do you dx HAV?

pt w/ clinical features of acute hepatitis & positive test for IgM anti-HAV.

67

Describe the serological tests associated w/ HBV.
HBsAg
HBeAg and HBV DNA
IgM anti-HBc
IgG anti HBc
Anti HBs
Anti HBe

HBsAg-ongoing HBV infection
HBeAg and HBV DNA- active viral replication, progression to chronic hepatitis
IgM anti-HBc- acute hepatitis
IgG anti HBc- past exposure to HBV
Anti HBs- recovery and immunity from HBV infection
Anti HBe- infection is resolving

68

How do you dx acute HBV?

Acute Hepatitis B =
pt w/ clinical features
HBsAg
IgM anti-HBc
both positive

*If pt has + HBsAg, but – IgM anti-HBc → think chronic hepatitis or carrier state

69

How do you dx chronic HBV?

clinical features & HBsAg + for > 6 mo.
• Also order HBeAg & HBV DNA to look for active viral replication

70

What serologic tests are used for HCV?

Anti-HCV Ab develop 10 wks post infection, do NOT confer recovery or immunity in most pts

71

What is the preferred screening test for HCV?

Ab detection using immunoassays = preferred screening test


72

How do you confirm an active HCV infection?


Active infection confirmed by measuring viral load by HCV PCR – used to assess response to therapy

73

Describe the serologic tests associated w/ HDV.
IgM anti-HDV
IgG anti-HDV
Anti-HDV
HDAg and HDV RNA

IgM anti-HDV- acute or recent HDV
IgG anti-HDV- previous infection w/ HDV, confers immunity
Anti-HDV- acute or chronic exposure
HDAg and HDV RNA- acute viral replication, ongoing infection

74

What serological marker persists in superinfecions w/ chronic HDV?

IgM anti-HDV can also persist

75

How do you dx HDV?

HBsAg positive
Evidence of HDV infection
— HDAg or HD RNA positive
— IgM anti-HDV positive
— anti-HDV positive

76

What marks an HDV coinfection?

IgM anti-HBc positive (acute or recent HBV

77

What marks an HDV superinfection?

IgM anti-HBc negative (chronic HBV)

78

How do you test for HDV?

— pts w/ high risk factors
— Present w/ unusually severe sx
— Acute hepatitis occurring in chronic HBV carrier

79

How do you detect acute HEV infections?

anti-IgM HEV & HEV RNA

80

WHat are the tests used to screen blood to avoid transfusion trasnmitted hepatitis?

• HBsAg
• anti-HBc
• HBV DNA
• anti-HCV
• HCV RNA

81

How is perinatally acquired HBV prevented?

Infants of mothers who are positive for hepatitis B surface antigen should receive hepatitis B immune globulin and hepatitis B vaccination within 12 hours of birth, and other infants should receive hepatitis B vaccination before hospital discharge.

82

What is the incubation phase of acute viral hepatitis?

variable, dependent on viral type

83

What are the 4 phases of the clincial presentation of acute viral hepatitis?

• Incubation phase: variable, dependent on viral type
• Preicteric prodrome: nonspecific, constitutional symptoms (malaise, fatigue, nausea, loss of appetite, arthralgias etc.); elevated serum levels of liver enzymes (ALT: alanine aminotransferase; AST: aspartate aminotransferase).
• Icteric (jaundice) phase: jaundice is not always present (anicteric hepatitis); conjugated hyperbilirubinemia mainly; dark urine (bilirubinuria).
• Convalescence (recovery) vs. acute liver failure vs. chronic hepatitis (with or without progression to cirrhosis) vs. “healthy” carrier.

84

How do you assess hte degree of liver damage w/ chronic viral hepatitis?

liver biopsy

clinical findings are highly variable

85

What are hte pathological findings associated w/ acute viral hepatitis?

lobular hepatitis
o Diffuse liver cell degeneration (ballooning degeneration)
o Focal hepatocellular necrosis (“dropout necrosis” – loss of hepatocytes) & apoptosis (councilman bodies)
o Confluent necrosis (seen in severe cases)
o Kupffer cell hyperplasia and hepatocellular regeneration
o Mononuclear inflammation (predominantly lymphocytes) w/in portal tracts and lobules
o "Lobular disarray"

86

Is acute viral hepatitis biopsied?

No

87

What defines chronic viral hepatitis?

hepatitis lasting more than 6 mos.

88

What pathological findings are associated w/ chronic hepatitis and ongoing necroinflammatory changes?

Periportal hepatitis
o Piecemeal necrosis
o Bridging necrosis & progressive fibrosis between periportal tracts → cirrhosis (severe cases)

89

Why is a biopsy required to assess liver damage in chronic viral hepatitis?

clinical findings of chronic viral hepatitis are highly variable

90

What is a councilman body?

apoptotic body in chronic viral hepatitis

91

Ground glass hepatocytes are associated w/...

chronic HBV

92

Spotty, focal pattern of mild periportal hepatitis with mild steatosis is associated w...

chronic HCV

93

What are some of the causes of acute massive hepatic necrosis?

o Acute viral hepatitis
o Drug/toxin induced hepatitis (acetaminophen OD = 50%)
o Vascular liver diseases
o Autoimmune hepatitis
o Wilson’s disease

94

If patients w/ acute massive hepatic necrosis survive, do they always get cirrhosis?

NO!

Pts suffer from acute liver failure

If pt survives, may not cause cirrhosis (if toxic agengent doesn’t cause fibrosis, liver can regenerate normally)

95

What abs are used to dx type 1 autoimmune hepatitis?

Type 1:
anti-nuclear (ANA),
anti-smooth muscle actin (SMA)
anti-soluble liver antigen/liver-pancreas (anti-SLA/LP) antibodies


96

What abs are used to dx type 2 autoimmune hepatitis?

Type 2:
anti-liver/kidney microsome-1 (anti-ALKM-1)
&/or
antibodies to a liver cytosol antigen (ALC-1)

97

What features seen on biopsy may suggest a dx of AIH?

Chronic hepatitis with increased plasma cells in the periportal lymphocytic inflammatory infiltrate along with lobular inflammation


98

What is the MC AIH and who does it commonly affect?

Type I
middle aged females

type II (children and adolescents)

99

How do you tx AIH?

immunosuppressive steroids

Differs from chronic viral hepatitis b/c you wouldn’t want to suppress the immune system to fight infxn.

100

What is seen on an acute hepatitis paneL/

• IgM anti-HAV
• HBsAg
• IgM anti-HBc
• Anti-HCV

101

What is seen on a chronic hepatitis panel?

• HBsAg
• Anti-HBs
• Anti-HBc
• Anti-HCV