Br Pathology: Liver, Gallbladder, Pancreas

Front 1

Where does unconjugated bilirubin come from?

Back 1

(1) Senescent RBCs are phagocytosed by splenic macrophages.
(2) UCB is the end-product of heme degradation.
a. UCB is lipid-soluble (indirect bilirubin)

Front 2

How is unconjugated bilirubin transported in the blood? Where it it transported?

Back 2

1) UCB combines with albumin in the blood
2) UCB is taken up by hepatocytes.
3) UCB is conjugated to glucuronic acid to produce conjugated bilirubin (CB).
a. CB is water soluble (direct bilirubin).

Front 3

Once conjugated bilirubin is made where does it go and what happens to it?

Back 3

1) CB is secreted into the intrahepatic bile ducts.
a. Temporarily stored in the gallbladder
b. Enters the duodenum via the common bile duct
2) Intestinal bacteria convert CB to urobilinogen (UBG).
a. UBG is spontaneously oxidized to urobilin.
b. Urobilin produces the brown color of stool.

Front 4

20% of urobolinogen is recycled from the intestine. Where is it eliminated? what gives urine its color?

Back 4

1) 90% goes to liver
2) 10% goes to kidney
a. urobilin gives urine its color

Front 5

What produces color of urine and stool?

Back 5

urobilin

Front 6

What is jaundice due to? Where does it first present?

Back 6

1) Jaundice is due to an increase in UCB and/or CB.
a. Jaundice is first noticed in the sclera
b. Sclera has a high affinity for bilirubin.

Front 7

How are causes of jaundice classified?

Back 7

1) Classification of causes of jaundice is based on the percentage of CB
2) Percent CB = CB/total bilirubin

Front 8

What is the 2nd most common cause of jaundice and has fasting unconjugated hyperbilirubinemia? What is the most common cause of jaundice?

Back 8

1) Gilberts disease
2) viral infection

Front 9

What are prodrome findings of acute viral hepatitis? When do transaminases peak in relation to jaundice?

Back 9

1. Fever
2. Painful hepatomegaly; distaste for alcohol/cigarettes
3. Serum transaminases increase steadily.
a. Peak just before jaundice occurs
4. Atypical lymphocytosis

Front 10

With acute viral hepatitis is there an increase in bilirubin, or urobilinogen or both?

Back 10

Increased urine bilirubin and urine UBG

Front 11

What are microscopic findings in acute viral hepatitis? What is an unfavorable sign and why?

Back 11

1. Lymphocytic infiltrate with destruction of hepatocytes
a. Apoptosis of hepatocytes (Councilman bodies)
2. Persistent inflammation and fibrosis is an unfavorable sign.
a. Sign of chronic hepatitis progressing to postnecrotic cirrhosis

Front 12

What is the most common viral cause of jaundice? Councilman bodies on microscopic exam are caused by?

Back 12

1) Hepatitis A
2) acute viral hepatitis

Front 13

Anti-HAV-IgM indicates what? what about Anti-HAV-IgG?

Back 13

1. Anti-HAV-IgM indicates active infection.
2. Anti-HAV-IgG indicates recovery from infection or vaccination.
a. Protective antibody

Front 14

What is the First marker of HBV infection? When does it first appear? How long does it persist?

Back 14

(1) Hepatitis B surface antigen (HBsAg)
a. Appears within 2 to 8 weeks after exposure
(2) Persists up to 4 months in acute hepatitis
a. HBsAg longer than 6 months defines chronic HBV.

Front 15

In relation to HBsAg when do Hepatitis B e antigen (HBeAg) and HBV-DNA appear and disappear?

Back 15

1) Appear after HBsAg and disappear before HBsAg
2) Infective particles

Front 16

What is the function of Anti-HBV core antibody IgM (anti-HBc-IgM)? When is present? When does it convert to anti-HBc-IgG?

Back 16

(1) Nonprotective antibody
a. Remains positive in acute infections
(2) Persists during "window phase" or "serologic gap"
a. HBsAg, HBV DNA, and HBeAg are absent.
(3) Converts entirely to anti-HBc-IgG by 6 months

Front 17

What is the only marker present during window phase of HBV?

Back 17

Anti-HBc-IgM

Front 18

When is Anti-HBc-IgG present?

Back 18

after 6 months of infection

Front 19

What is the function of Anti-HBV surface antibody (anti-HBs)?

Back 19

(1) Protective antibody
(2) Marker of immunization after HBV vaccination or post-recovery

Front 20

What does Anti-HBs indicate?

Back 20

1) immunization
2) recovery from past infection

Front 21

What are indications of chronic HBV infection? what are findings in "healthy" chronic carrier state and is person still contagious?

Back 21

(1) Persistence of HBsAg longer than 6 months
a. Anti-HBc-IgM converts to anti-HBc-IgG
(2) "Healthy" chronic carrier
a. Presence of HBsAg and anti-HBc-IgG
b. Absence of DNA and e antigen
c. Still contagious but at a much lower risk

Front 22

How do you know if someone is an infective chronic carrier of HBV? What are they at risk of?

Back 22

(a) Presence of HBsAg, anti-HBc-IgG, and infective particles (DNA and e antigen)
(b) Increased risk for postnecrotic cirrhosis and hepatocellular carcinoma

Front 23

An enzyme immunoassay (EIA) is used to detect HCV. What is measured? Is it sensitive or specific? Is a protective antibody?

Back 23

(1) Presence of anti-HCV-IgG indicates active infection or recovery.
a. Sensitivity > 97%
(2) It does not differentiate among acute, chronic, or resolved infection.
(3) It is not a protective antibody

Front 24

HCV is screened with an enzyme immunoassay. What are more specific tests?

Back 24

(1) Recombinant immunoblot assay (RIBA)
a. Supplemental test if EIA is positive
b. More specific but less sensitive than EIA
(2) HCV RNA using polymerase chain reaction
a. Gold standard test for diagnosing HCV
b. Detects virus as early as 1 to 2 weeks after infection
c. Used to monitor patients on antiviral therapy
(3) Positive RIBA and HCV RNA indicate active infection.
(4) Positive RIBA and negative HCV RNA indicate recent recovery

Front 25

What serum markers are used to determine if someone is infected with HDV?

Back 25

1) Presence of anti-HDV-IgM or IgG indicates active infection.
a. IgG is not a protective antibody.

Front 26

What serum markers are used to detect HEV?

Back 26

1. Presence of anti-HEV-IgM indicates active infection.
2. Anti-HEV-IgG indicates recovery (protective antibody).

Front 27

How are serum bilirubin levels affected by viral hepatitis?

Back 27

1) CB 20% to 50% (mixed hyperbilirubinemia)
a. Decreased uptake/conjugation of UCB
b. CB gains access to blood via damaged bile ductules.
Note: both types increase

Front 28

Are both urine UBG and urine bilirubin increased in viral hepatitis?

Back 28

1) Increased urine UBG and urine bilirubin
a. CB is water soluble and is filtered in the kidneys.
b. UBG recycled back to inflamed liver is redirected to the kidneys

Front 29

How are serum tranaminases affected by viral hepatitis?

Back 29

1. Serum ALT is greater than AST.
2. Serum ALT is the last liver enzyme to return to normal.

Front 30

What are reasons for conjugated bilirubin being less than 20%?

Back 30

1) Increased production of UCB
2) Decreased uptake or conjugation of UCB

Front 31

What are causes that increase unconjugated bilirubin but have a conjugated bilirubin <20%? Is urine bilirubin present or absent? Is urine urobilinogen increased or decreased?

Back 31

1) Extravascular hemolytic anemias:
a. spherocytosis
b. Rh and ABO HDN
c. warm AIHA
2) absent
3) increased

Front 32

What are diseases that have Decreased uptake or conjugation of UCB? Is urine bilirubin present or absent? Is urine urobilinogen increased or decreased?

Back 32

Examples:
a. Gilbert's syndrome (familial nonhemolytic jaundice)
b. Crigler-Najjar syndromes
c. Physiologic jaundice of newborn
d. Breast milk jaundice
2) absent
3) normal urobilinogen

Front 33

Gilbert's syndrome is also known as? What are genetics? Are females or males affected more? Does direct or indirect bilirubin increase?

Back 33

1) familial nonhemolytic jaundice
2) common AR or AD defect (depends on the type of mutation)
3) occurs in >5% of population
a. second most common jaundice (hepatitis most common)
b. most common hereditary cause of jaundice
3) males > females
4) indirect bilirubin

Front 34

What is defect in Gilberts syndrome? When does jaundice occur? what level do unconjugated bilirubin levels rarely exceed? What do liver function tests show?

Back 34

1) impaired glucuronyl transferase activity (70-75% decrease in activity)
2) jaundice occurs with fasting or increase in alcohol or phenobarbital intake
3) serum UCB rarely >5 mg/dL
4) all other liver function tests are normal
5) liver biopsy not necessary
6) no treatment required

Front 35

Crigler-Najjar syndrome has a genetic deficiency in what? there are two forms. What occurs in each? What can help if deficiency isn't complete?

Back 35

1) decreased to absent glucuronyl transferase enzyme
2) absent type = early death from kernicterus where damage has occurred to basal ganglia and other parts of CNS from unconjugated bilirubin
3) partially present type = responds to phenobarbital therapy which decreases serum concentration of UCB

Front 36

When does physiologic jaundice of the newborn begin? Why?

Back 36

1) begins on day 3 of life
2) caused by normal macrophage destruction of fetal RBCs and inability of newborn liver to handle excess load

Front 37

What is breast milk jaundice due to? What is treatment?

Back 37

1) due to pregnane-3α,20α-diol
2) does not require treatment

Front 38

What are causes of Mixed CB 20-50%? Why? Is there bilirubin in the urine? Is the rate of urobilinogen in urine increased or decreased?

Back 38

1) Viral hepatitis causes:
a. defect in uptake
b. conjugation of UCB
c. secretion of CB
2) increased urine bilirubin
3) increased urine urobilinogen

Front 39

What are causes of obstruction leading to hyperbilirubinemia with conjugated bilirubin >50% total serum concentration? Is bilirubin present or absent in the urine? Is urine urobilinogen increased or decreased?

Back 39

1) Decreased intrahepatic bile flow
2) Drug-induced (e.g., OCP)
3) Primary biliary cirrhosis
4) Dubin-Johnson syndrome
5) Rotor's syndrome
6) Decreased extrahepatic bile flow
7) Gallstone in common bile duct
8) Carcinoma of head of pancreas
9) bilirubin present in urine
10) urobilinogen decreased or absent from urine

Front 40

What are genetics of Dubin-johnson syndrome? What is defect?

Back 40

1) AR disorder
2) defective bilirubin transport into intrahepatic bile ducts
3) black pigment in hepatocytes

Front 41

What are genetics of rotors syndrome? How is it different than dubin-johnson

Back 41

1) AR disorder similar to Dubin-Johnson syndrome but without black pigment in hepatocytes

Front 42

In extravascular hemolysis which hepatic aminotransferase will be elevated?

Back 42

1) AST slightly increased
2) ALT normal
3) GGT normal
4) ALP normal

Front 43

In viral hepatitis how are AST, ALT, GGT and ALP affected?

Back 43

1) ALT > AST both increased
2) GGT increased slightly
3) ALP increased slightly

Front 44

In obstructive hepatitis how are AST, ALT, GGT and ALP affected?

Back 44

1) AST increased
2) ALT increased
3) ALP and GGT very high
Note: Stool will not be brown because urobilin is not present

Front 45

Go over entire pathway of normal bilirubin metabolism! Why is unconjugated bilirubin never found in urine normally?

Back 45

Normal bilirubin metabolism: liver uptake of lipid-soluble unconjugated bilirubin (UCB) and its conjugation with glucuronic acid to produce water-soluble conjugated bilirubin (CB). CB is secreted into the common bile duct (CBD) and is emptied into the bowel. Intestinal bacteria convert CB to urobilinogen (UBG), which spontaneously oxidizes to the pigment urobilin. Urobilin is responsible for the color of stool. A small percentage of UBG is reabsorbed into the blood. Most of it enters the liver and a small percentage enters the urine (UBG). Urobilin is responsible for the color of urine. All of the normal bilirubin in blood is UCB (CB% < 20%) primarily derived from macrophage destruction of senescent RBCs. UCB does not enter urine, because it is attached to albumin in the blood and is lipid, not water, soluble. CB is never a normal finding in urine because it does not have contact with blood in its metabolism.

Front 46

Pathogenesis of extravacular hemolysis?

Back 46

In extravascular hemolysis (B) (e.g., hereditary spherocytosis), there is increased macrophage production of UCB causing an increase in serum UCB (++) (CB% < 20%). There is a corresponding increase in uptake and conjugation of UCB, conjugation to CB (++), and conversion of CB in the bowel to UBG (++). This causes darkening of the stool. There is a greater percentage of UBG recycled back to the liver and urine. The increase in urine UBG (++), darkens the color of urine. Because RBCs contain the enzyme aspartate aminotransferase (AST), hemolysis of RBCs causes an increase in serum AST. Alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) levels are normal

Front 47

Pathogenesis of viral hepatitis?

Back 47

In viral hepatitis (C), there is generalized liver dysfunction involving uptake and conjugation of UCB, secretion of CB into bile ducts, and recycling of UBG. Serum UCB is increased (++) owing to a decrease in uptake and conjugation. Serum and urine CB are increased (++) because of liver cell necrosis and disruption of bile ductules between hepatocytes. Urine UBG is increased (++) because UBG is redirected from the liver to the kidneys. Because there is an increase in serum UCB and CB, there is a mixed hyperbilirubinemia with a CB% of 20% to 50%. In viral hepatitis, aLT is higher (+++) than AST (++) and there is a slight increase in ALP and GGT (+). In alcoholic hepatitis, AST is greater than ALT, because alcohol damages mitochondria, which is where AST is normally located

Front 48

Pathogenesis of obstructive liver disease?

Back 48

In obstructive liver disease (D), an increase in serum and urine CB (++) is due to obstruction of intrahepatic or extrahepatic bile flow (stone in the CBD in this case). This causes increased pressure in the intrahepatic bile ductules leading to rupture and egress of CB into sinusoidal blood. There is absence of UBG in the stool (light-colored) and urine. CB% > 50% and there is a marked increase in serum ALP and GGT (+++) and only a slight increase in serum AST and ALT (+)

Front 49

Where is ALT found in the hepatocyte? is ALT or AST specific for liver cell necrosis?

Back 49

1) ALT = Specific enzyme for liver cell necrosis
2) Present in the cytosol
3) ALT > AST: viral hepatitis

Front 50

Where in cell is AST found? What does it indicate with AST>ALT?

Back 50

1) Present in mitochondria
2) Alcohol damages mitochondria:
a. AST > ALT indicates alcoholic hepatitis

Front 51

When is GGT elevated?

Back 51

1) Intra- or extrahepatic obstruction to bile flow
2) Induction of cytochrome P-450 system (e.g., alcohol): increases GGT

Front 52

What does it mean if GGT is normal but ALP is increased? what does it mean if GGT and ALP are both increased?

Back 52

1) Normal GGT and increased ALP:
a. source of ALP other than liver (e.g., osteoblastic activity in bone)
2) Increased GGT and ALP:
a. liver cholestasis

Front 53

Urine bilirubin indicates what?

Back 53

1) Bilirubinuria:
a.viral hepatitis
2) intra- or extrahepatic obstruction of bile ducts
2)

Front 54

Increased urine urobilinogen means what? decreased?

Back 54

1) Increased urine UBG:
a. extravascular hemolytic anemias, viral hepatitis
2) Absent urine UBG:
a. liver cholestasis

Front 55

What are general markers of liver function?

Back 55

1) Serum albumin
2) Prothrombin time (PT)
3) Blood urea nitrogen (BUN)
4) Serum ammonia

Front 56

Decreased BUN, increased PT, increased serum ammonia and hypoalbuminemia are all signs of what? Why?

Back 56

1) liver disease
2) Majority of coagulation factors are synthesized in the liver
a. Increased PT: severe liver disease
3) Urea cycle is present in the liver
a. Decreased serum BUN: cirrhosis
4) Ammonia is metabolized in the urea cycle in the liver
a. Derives from large bowel and amino acid degradation
b. Increased serum ammonia: cirrhosis, Reye syndrome
5) Albumin is synthesized by the liver
a. Hypoalbuminemia: severe liver disease (e.g., cirrhosis)

Front 57

Which antibodies are used to determine Primary biliary cirrhosis?
Autoimmune hepatitis? Increased in primary biliary cirrhosis? what is tumor marker for hepatocellular carcinoma?

Back 57

1) PBC = Antimitochondrial antibody
2) AH = Anti-smooth muscle antibody and Antinuclear antibody (ANA)
3) Serum IgM
4) AFP

Front 58

In viral hepatitis how are the following affected in relation to eachother:
1) %conjugated bilirubin
2) AST
3) ALT
4) ALP
5) GGT
6) urine bilirubin
7) urine urobilinogen

Back 58

1) %conjugated bilirubin = 20-50%
2) AST = ↑↑↑
3) ALT = ↑↑↑↑
4) ALP = ↑
5) GGT= ↑
6) urine bilirubin = ↑↑
7) urine urobilinogen = ↑↑

Front 59

In alcoholic hepatitis how are the following affected in relation to eachother:
1) %conjugated bilirubin
2) AST
3) ALT
4) ALP
5) GGT
6) urine bilirubin
7) urine urobilinogen

Back 59

1) %conjugated bilirubin = 20-50%
2) AST = ↑↑
3) ALT = ↑
4) ALP = ↑
5) GGT = ↑↑↑
6) urine bilirubin = ↑↑
7) urine urobilinogen = ↑↑

Front 60

In Cholestasis how are the following affected in relation to eachother:
1) %conjugated bilirubin
2) AST
3) ALT
4) ALP
5) GGT
6) urine bilirubin
7) urine urobilinogen

Back 60

1) %conjugated bilirubin = >50%
2) AST = ↑
3) ALT = ↑↑
4) ALP = ↑↑↑
5) GGT = ↑↑↑
6) urine bilirubin = ↑↑↑
7) urine urobilinogen = Absent

Front 61

In Extravascular hemolysis how are the following affected in relation to eachother:
1) %conjugated bilirubin
2) AST
3) ALT
4) ALP
5) GGT
6) urine bilirubin
7) urine urobilinogen

Back 61

1) %conjugated bilirubin = <20%
2) AST = ↑↑ from RBCs
3) ALT = N
4) ALP = N
5) GGT = N
6) urine bilirubin = absent
7) urine urobilinogen = ↑↑

Front 62

Who is HAV a common infection in?

Back 62

1) Accounts for 37% of acute hepatitis in U.S.
2) Most preventable infection in travelers
3) Increased incidence in children/employees in day care centers, prisons, travelers to developing countries, males who have sex with males (anal intercourse), parents adopting children from other countries

Front 63

What is the incubation period of HAV? What is its clinical coarse? who can be immunized? How long does it take to develop immunoglobulins to?

Back 63

1) Infectious hepatitis
2) Incubation 15-50 days (average 30 days)
3) Clinical:
a. jaundice > 70%; fever
b. nausea/vomiting
c. abdominal pain
4) Majority recover; no carrier state; no chronic hepatitis
5) Passive immunization: immunoglobulin (passive transfer of antibodies) for pre-exposure prophylaxis and postexposure prophylaxis
6) Active immunization: protective antibodies in 1 month

Front 64

How is HBV transmitted? What is incubation period? How is chronic form treated?

Back 64

1) Parenteral, orally, sexual, vertical (pregnancy, breast feeding)
a. Primarily spread via blood (IVDA) and sexually
2) Incubation 30-180 days
3) Treatment of chronic hepatitis:
a. pegylated IFN-α
b. nucleoside analogues that block viral replication (e.g., lamivudine; entecavir); liver transplant

Front 65

How does HBV present clinically? What does the serum sickness prodrome consist of?

Back 65

1) Clinical:
a. variable fever
b. profound malaise
c. painful hepatomegaly (87%)
2) serum sickness prodrome (15-20%):
a. immunocomplex disease (HBsAg + antibody)
b. vasculitis (polyarteritis nodosa)
c. urticaria
d. polyarthritis
e. membranous glomerulopathy

Front 66

How many people are likely to recover from HBV? Who is more likely to develop chronic form? What are complications of HBV in liver?

Back 66

1) Recovery in >90% of immunocompetent patients
a. 1-2% develop chronic hepatitis
2) Newborns and immunodeficient patients more likely to develop chronic hepatitis (>90%)
3) Complications:
a. fulminant hepatitis <1% especially if coinfected with hepatitis D
b. hepatocellular carcinoma secondary to postnecrotic cirrhosis

Front 67

How is HCV transmitted? What is the incubation period?

Back 67

1) Parenteral, sexual
a. Most cases due to IVDA (60%)
b. hemophiliacs transfused before 1987
c. Post-transfusion hepatitis rare due to screening
d. Maternal-fetal transmission is infrequent (estimated 5%)
2) Incubation 2-26 weeks (average, 6-7 weeks)

Front 68

What is the Most common main indication for liver transplantation in U.S.? What are clinical findings?

Back 68

1) HCV
2) Clinical:
a. mild hepatitis (70-80% subclinical)
b. jaundice uncommon (80% anicteric)
3) Chronic hepatitis in >70% of cases
4) Other clinical associations:
a. type I membranoproliferative glomerulonephritis
b. alcohol excess
c. porphyria cutanea tarda
d. lichen planus
e. B cell lymphoma

Front 69

What can HCV lead to in the liver? How is it prevented? How is it treated?

Back 69

1) Complications: hepatocellular carcinoma secondary to postnecrotic cirrhosis
2) Prevention: no preventive vaccine available
3) Treatment:
a. early treatment of acute infection with pegylated IFN-α may prevent chronic infection
b. pegylated IFN-α also used in treating chronic HCV
c. liver transplant

Front 70

HDV requires what for infection? Is it more likely to create a chronic carrier state or a fulminant superinfection? How is it prevented?

Back 70

1) Incomplete RNA virus that requires HBsAg to replicate
2) Chronic state less likely with coinfection (HBV and HDV exposure at same time) than superinfection (HBV carrier exposed to blood containing HBV and HDV)
3) Chronic infection develops in 60-85% of people infected
4) Prevention: immunization with recombinant vaccine for HBV

Front 71

where does HEV infection occur? What does it usually produce? What can it do in pregnant women?

Back 71

1) Occurs in developing countries
2) Only produces acute hepatitis
3) Fulminant hepatitis may develop in pregnant women

Front 72

Approximately when is anti-HBc IgM present? When is anti-HBc IgG present? What is first antigen found and when does it appear and disappear?

Back 72

1) anti-HBc IgM ~2 months to 6 months
2) anti-HBc IgG seen at about 4 months and remains for years
3) HBsAg found ~1 month till 4 months

Front 73

When are HBeAg and HBV DNA first seen and when are they gone? When is anti-HBe seen and when is it gone? When is anti-HBs seen?

Back 73

1) ~1.5 months remains till 3.5 to 4 months
2) ~5.5 months till 2 years
3) ~5 months and present for a few years

Front 74

HBsAg is only seen? HBsAg, HBeAg, and anti-HBc IgM are seen?

Back 74

1) earliest phase of acute HBV infection
2) acute infection

Front 75

Only anti-HBc IgM is seen? anti-HBc IgG and anti-HBs only are detected?

Back 75

1) window phase or serologic gap
2) HBV recovery

Front 76

anti-HBs only is seen? HBsAg, and anti-HBc IgG are seen?

Back 76

1) immunized person
2) "healthy" carrier

Front 77

HBsAg, HBeAg and DNA are seen with anti-HBc IgG?

Back 77

infective carrier

Front 78

What is the most common autoimmune hepatitis? Who does it occur in? What are possible symptoms?

Back 78

1) type I
2) Occurs most often in young women
3) Range of presentations
a. Symptomatic with increased transaminases
b. Fulminant hepatitis
c. Cirrhosis

Front 79

What are genetic associations of type I autoimmune hepatitis? What other immune conditions can it be seen with?

Back 79

1) Human leukocyte antigen (HLA) DR3 and DR4 association
2) Other autoimmune associations
a. Examples-Hashimoto's thyroiditis, Graves' disease

Front 80

Clinically how does type I autoimmune hepatitis present? How is it treated?

Back 80

1) Clinical findings:
a. Fever
b. Jaundice
c. Hepatosplenomegaly
2) Treatment:
a. Initial treatment with corticosteroids + azathioprine
b. Liver transplantation if resistant to therapy

Front 81

What are common lab findings in autoimmune hepatitis? Which antibodies are associated with it?

Back 81

1) Laboratory findings for type 1
a. Positive serum antinuclear antibody (ANA) test (>60%)
b. Anti-smooth muscle antibodies (>85%)
c. Increased serum transaminases
d. Decreased serum albumin in severe disease
e. Prolonged prothrombin time in severe disease

Front 82

What are causes of neonatal hepatitis? What does a biopsy show?

Back 82

1. Idiopathic
2. Associated with congenital infections
a. Example-cytomegalovirus
3. Associated with inborn errors of metabolism
a. Example-α1-antitrypsin deficiency
2 Biopsy shows multinucleated giant cells.
a. "Giant cell" hepatitis

Front 83

What is the post-infectious triad of Reyes syndrome? What is disease associated with?

Back 83

(1) Encephalopathy
(2) Microvesicular fatty change
(3) Transaminase elevation
(4) association with aspirin and infection (chickenpox, influenza)

Front 84

Pathologically what occurs in Reyes syndrome?

Back 84

1. Mitochondrial damage (? virus, salicylates)
2. Disruption of the urea cycle
a. Increase in serum ammonia
3. Defective β-oxidation of fatty acids from salicylates
4. Microvesicular fatty change (? salicylate effect)
a. Small cytoplasmic globules without nuclear displacement
b. No inflammatory infiltrate

Front 85

How does Reyes syndrome present and progress?

Back 85

1. Initially afebrile, quiet, lethargic, sleepy, and vomiting
a. Hepatomegaly and liver dysfunction present
2. Encephalopathy findings in progression
a. Signs and symptoms related to cerebral edema and increasing pressure
(1) Sleepy but respond; vomiting
(2) Stuporous, seizures, decorticate rigidity, intact papillary reflexes
(3) Deepening coma, decerebrate rigidity, fixed pupils
(4) Coma, loss of deep tendon reflexes, fixed dilated pupils, flaccidity/decerebrate
(5) Death

Front 86

What are laboratory findings in Reyes syndrome?

Back 86

1. Transaminasemia
2. Normal to slight increase in total bilirubin
3. Increased serum ammonia and prothrombin time (PT)
a. Levels predict degree of severity
4. Hypoglycemia
5. Cerebrospinal fluid usually normal

Front 87

How is Reyes syndrome treated? What is prognosis?

Back 87

1. Supportive
2. Mannitol, glycerol, or hyperventilation to reduce cerebral edema
3) Approximately 25% to 50% mortality rate

Front 88

When does fatty liver during pregnancy occur? What is pathology? What must be done?

Back 88

1) third trimester
2) microvesicular fatty liver due to Abnormality in β-oxidation of fatty acids
3) Fatal to mother and fetus unless the baby is delivered

Front 89

What are findings in preeclampsia? What is HELLP syndorme? what happens to the liver?

Back 89

1) Hypertension
2) proteinuria
3) dependent pitting edema in third trimester
4) HELLP
a. Hemolytic anemia with schistocytes
b. Elevated serum transaminases
c. Low platelets
** Due to disseminated intravascular coagulation
5) Liver cell necrosis around portal triads (zone 1)
a. Increased serum transaminases

Front 90

What does fulminant liver mean? What are causes?

Back 90

1) Acute liver failure with encephalopathy within 8 weeks of hepatic dysfunction
2) Causes:
a. Viral hepatitis (most common overall cause)
b. Drugs (e.g., acetaminophen most common cause)
c. Reye syndrome

Front 91

How does the liver look on gross and microscopic exam in fulminant liver?

Back 91

1. Wrinkled capsular surface due to loss of hepatic parenchyma
2. Dull red to yellow necrotic parenchyma with blotches of green (bile)

Front 92

What are clinical and laboratory findings in fulminant liver?

Back 92

1) findings:
b. Hepatic encephalopathy
a. jaundice
2) Laboratory findings:
a. Decrease in transaminases
b. Liver parenchyma is destroyed.
2. Increase in PT and ammonia

Front 93

What bacteria generally causes Ascending cholangitis? what happens pathologically? How is it treated?

Back 93

1) E. coli
2) Inflammation of bile ducts (cholangitis) from concurrent biliary infection and duct obstruction (e.g., stone)
2) Life-threatening disease
3) Treatment: decompression and drainage; piperacillin-tazobactam

Front 94

What is the Most common cause of multiple liver abscesses? What is the triad?

Back 94

1) Ascending cholangitis from Escherichia coli
2) Triad:
a. fever
b. jaundice
c. RUQ pain

Front 95

What are 3 bacterial causes of liver abscesses? How are they treated? What are clinical features? is jaundice common?

Back 95

1) Escherichia coli
2) Bacteroides fragilis
3) Streptococcus faecalis
4) Treatment: percutaneous drainage; metronidazole + ceftriaxone
5) Clinical:
a. spiking or intermittent fever
b. RUQ or right costovertebral angle tenderness
c. jaundice is uncommon

Front 96

What pathogens causes granulomatous hepatitis?

Back 96

1) Mycobacterium tuberculosis
2) Histoplasma capsulatum

Front 97

Spontaneous peritonitis in adults is caused by? in children? What develops clinically in each? How is each treated?

Back 97

1) Escherichia coli in adults
2) Streptococcus pneumoniae in children
3) Develops in ascites (e.g., cirrhosis, nephrotic syndrome)
4) Treatment: cefotaxime

Front 98

What are features of Leptospira interrogans?

Back 98

1) Gram-negative
a. tightly wound spirochetes
b. crook at the end resembles a shepherd's staff or ?
2) Reservoirs: rats, dogs (most common); spirochetes excreted in urine
3) Transmission: swimming in contaminated water (ponds on farms); farmers, miners, people who work with sewage
4) Treatment: penicillin G

Front 99

Leptospirosis causes a biphasic disease known as? what are the two phases and what occurs in each? What marks the end of the first phase? How is the urine examined?

Back 99

1) Weil's disease
2) Septicemic phase:
a. fever
b. jaundice
c. hemorrhagic diathesis
d. renal failure (interstitial nephritis)
e. conjunctivitis and photophobia
f. meningitis
g. phase terminated by the appearance of antibodies (beginning of immune phase)
3) Immune phase:
a. presence of numerous organisms in the urine
b. urine best examined by darkfield microscopy to confirm the diagnosis

Front 100

What is the Most common cause of a liver abscess worldwide (not in the United States)? Which lobe of liver commonly involved? How is it treated?

Back 100

1) entamoeba hystolytica
a. E coli most common in US
2) Usually produces a right lobe abscess
3) Treatment: metronidazole followed by paromomycin

Front 101

Clonorchis sinensis is also known as? What type of organism is it? How is it contracted? What cancer is person predisposed to? How is it treated?

Back 101

1) (Chinese liver fluke)
2) Intestinal fluke (trematode)
3) Contracted by ingesting encysted larvae in fish
a. larvae enter common bile duct and become adults.
3) May produce cholangiocarcinoma
4) Treatment: praziquantel

Front 102

What is the lifecycle of Clonorchis sinensis (Chinese liver fluke)?

Back 102

Nonschistosomal life cycle: egg (human) → ciliated miracidial larva → infects snail (1st intermediate host) → produce fork-tailed cercarial larvae → infect a 2nd intermediate host (fish in clonorchiasis) → form infective metacercariae → man ingests the 2nd intermediate host → develops disease

Front 103

What type of organism is Schistosoma mansoni?

Back 103

1) Fluke (trematode)
2) Schistosomal life cycle: egg (human) → ciliated miracidial larva → infects snail (1st intermediate host) → produce fork-tailed cercarial larvae → penetrate skin in human → produce disease

Front 104

What is pathogenesis of Schistosoma mansoni? What sign is seen?

Back 104

1) larvae in the superior mesenteric vein enter into the portal vein
2) they develop into adult worms that deposit eggs
3) the host develops an inflammatory response marked by concentric fibrosis ("pipestem cirrhosis") in the vessel wall

Front 105

What are complications of S mansoni?

Back 105

1) Complications of cirrhosis:
a. portal hypertension
b. ascites
c. esophageal varices
Treatment:
a. praziquantel

Front 106

Echinococcus granulosus is also known as? what type of organism? where can cysts be found?

Back 106

1) (sheepherder's disease)
2) Intestinal tapeworm (cestode)
3) Single or multiple cysts containing larval forms;
4) cysts can be in the liver (most common site), lungs, and brain

Front 107

What is life cycle of Echinococcus granulosus? What are all the intermediate hosts?

Back 107

1) Eggs develop into a larval form only
a. larval form only develops into an adult, which can lay eggs
2) Infected sheep is intermediate host (larval form in liver cyst)
a. dog that eats the sheep liver is the definitive host (larva develops into adults, which produce eggs)
b. human who eats the eggs from the dog becomes the intermediate host (eggs develop into larvae, which penetrate the bowel and enter the liver to produce the hydatid cyst)

Front 108

How can Echinococcus granulosus be treated? What are larvae called? What can rupture of cysts produce? How is it treated?

Back 108

1) Can be contracted by children eating grass contaminated with dog excreta
2) Inner germinal layer of hydatid cysts has protoscolices (larva) in brood capsules
3) Rupture of cysts can produce anaphylaxis
4) Treatment: percutaneous drainage + albendazole
Note: causes hydatid disease inliver

Front 109

How does yellow fever effect the liver? What is microsocpic finding? What type of virus is it?

Back 109

1) causes midzonal necrosis
2) dying hepatocytes condense into eosiophilic contracted forms called COUNCILMAN BODIES
a. similar to other viral causes of councilman bodies (eosinophilic bodies)
3) enveloped +ssRNA virus of the Flaviviridae family has icosahedral capsid
4) causes black vomitus

Front 110

Why is hepatic artery thrombosis uncommon? When it does happen what are the causes?

Back 110

1) Liver infarction is uncommon because of a dual blood supply.
a. Hepatic artery and portal vein tributaries normally empty blood into the sinusoids
2) Causes:
a. Liver transplant rejection
b. Vasculitis due to polyarteritis nodosa (PAN)

Front 111

What are causes of portal vein thrombosis?

Back 111

(1) Pylephlebitis (inflammation of portal vein)
a. Most often due to acute appendicitis
b. Air in portal vein from bacterial gas
(2) Polycythemia vera
(3) Hepatocellular carcinoma
a. Tumor invasion of the portal vein

Front 112

Clinically what is seen in portal vein thromobsis? Is there hepatosplenomegaly?

Back 112

(1) Portal hypertension, ascites, splenomegaly
(2) No hepatomegaly

Front 113

What are causes of intrahepatic blood flow obstruction?

Back 113

1) Cirrhosis
2) Centrilobular hemorrhagic necrosis
3) Peliosis hepatis
4) Sickle cell disease

Front 114

What is Centrilobular hemorrhagic necrosis most often due to?

Back 114

1) Most often due to left-sided heart failure (LHF) and right-sided heart failure (RHF)
2) LHF decreases cardiac output causing hypoperfusion of the liver.
a. Causes ischemic necrosis of hepatocytes located around central vein
3) RHF causes a backup of systemic venous blood into the central veins and sinusoids.

Front 115

When the liver is Enlarged with a mottled red appearance it is called? What is pathogenesis?

Back 115

1) "nutmeg" liver
a. Congestion of central veins and sinusoids
b. Necrosis of hepatocytes around the central vein

Front 116

Clinically what is seen in intrahepatic obstruction?

Back 116

(1) Painful hepatomegaly with or without jaundice
(2) Increased transaminases caused by ischemic necrosis
(3) May progress to cardiac cirrhosis
a. Fibrosis around central veins

Front 117

What is Peliosis hepatis? What are causes? what can potentially happen?

Back 117

1) Sinusoidal dilation due to blood
a. there are blood filled cavities throughout liver
2) Anabolic steroids
3) Bartonella henselae causing bacillary angiomatosis
a. Occurs in AIDS
4) Potential for intraperitoneal hemorrhage

Front 118

What are causes of post-hepatic blood flow obstruction?

Back 118

1. Hepatic vein thrombosis
2. Veno-occlusive disease

Front 119

What are causes of hepatic vein thrombosis?

Back 119

(1) Polycythemia vera
a. Most common cause (up to 40% of cases)
(2) Hypercoagulable state (20% of cases)
a. Oral contraceptive pills
b. Protein C/S deficiency
c. Antiphospholipid syndrome
(3) Hepatocellular carcinoma (<5% of cases)
a. Invades hepatic vein

Front 120

Clinically what is seen with a hepatic vein thrombosis?

Back 120

(1) Enlarged, painful liver
(2) Portal hypertension, ascites, splenomegaly
(3) High mortality rate
Laboratory findings
(1) Increased transaminases
(2) Increased PT

Front 121

How is hepatic vein thrombosis diagnosed? treated? what is prognosis?

Back 121

1) Diagnosis
a. Ultrasound with pulsed Doppler first-line test
b. MRI
2) Treatment
a. Anticoagulation
b. In situ thrombolysis
c. Stenting, various shunts
3) Prognosis
a. Approximately 75% mortality rate in first year

Front 122

the hepatic vein can become occluded from veno-occlusive disease. What is veno-occlusive disease a complication of?

Back 122

1. Complication of bone marrow transplantation
2. Collagen develops around the central veins.

Front 123

What is Hematobilia?

Back 123

Blood in the bile in patients with trauma to the liver

Front 124

Fatty change is the most common alcoholic liver manifestation. How does it occur? What are clinical features and treatment?

Back 124

(1) Substrates of alcohol metabolism are used to synthesize liver triglyceride.
(2) Clinical findings
a. Tender hepatomegaly without fever or neutrophilic leukocytosis
(3) Treatment
a. Alcohol rehabilitation

Front 125

What is the pathogenesis of alcoholic hepatitis?

Back 125

(a) Genetic predisposition is likely.
(b) Due to acetaldehyde damage to hepatocytes
(c) Stimulation of collagen synthesis around the central vein
a. Perivenular fibrosis (irreversible)
b. central hyaline sclerosis can occur
c. these can lead to central vein obstruction

Front 126

Microscopically what is seen in alcoholic hepatitis?

Back 126

(a) Fatty change with neutrophil infiltration and focal necrosis
(b) Mallory bodies (eosinophilic intracytoplasmic hyaline inclusions)
** Damaged cytokeratin intermediate filaments in hepatocytes
(c) Perivenular fibrosis
(d) May be macrovesicular from hepatic steatosis but becomes MICRONODULAR with cirrhosis (hobnail appearance)

Front 127

Clinically how does someone with alcohol hepatitis present? What can it progress to?

Back 127

(a) Painful hepatomegaly
(b) Fever, neutrophilic leukocytosis, ascites, hepatic encephalopathy
(c) May progress to alcoholic cirrhosis

Front 128

Laboratory findings in alcoholic hepatitis include?

Back 128

(a) Absolute neutrophilic leukocytosis
(b) Serum aspartate aminotransferase (AST) > alanine aminotransferase (ALT)
(c) Increased serum alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT)
** Serum GGT disproportionately increase to ALP
(d) Thrombocytopenia in some cases
(e) Hypoglycemia in some cases
Note: will have hobnail MICRONODULAR appearance with cirrhosis

Front 129

What is intrahepatic cholestatsis? What are causes?

Back 129

1. Blockage of the intrahepatic bile ducts
2. Causes
a. Drugs (e.g., oral contraceptive pills [OCPs], anabolic steroids)
b. Neonatal hepatitis
c. Pregnancy-induced cholestasis (estrogen)

Front 130

What is extrahepatic cholestasis? What are some causes?

Back 130

1. Blockage of common bile duct (CBD)
2. Causes
a) Stone usually originating from the gallbladder
b) Primary sclerosing cholangitis
c) Extrahepatic biliary atresia
d) Carcinoma head of pancreas

Front 131

What are gross and microscopic findings in cholestatic liver disease?

Back 131

1. Enlarged, greenish liver
2. Bile ducts distended with bile, bile lakes, bile infarcts

Front 132

What are clinical findings in cholestatic liver disease from intra/extrahepatic duct cholestastis?

Back 132

1. Jaundice with pruritus
a. Pruritus due to bile salts deposited in skin
2. Malabsorption
a. Bile salts do not enter the small intestine.
3. Cholesterol deposits in skin
a. Due to cholesterol in bile
b. Example-xanthelasma
4. Light-colored stools
a. Due to a lack of urobilin

Front 133

What are some laboratory findings in intra/extrahepatic cholestasis?

Back 133

1) CB > 50%
2) Bilirubinuria
3) Absent urine UBG
4) Increase in serum ALP and GGT

Front 134

What is Benign intrahepatic cholestasis of pregnancy due to? How dangerous is it to the mom and fetus?

Back 134

1. Due to estrogen inhibition of intrahepatic bile secretion
2. Not dangerous to the fetus or mother

Front 135

Who does extrahepatic duct biliary atresia occur in? What is effected? What is it an indication of?

Back 135

1. Cause of jaundice in newborns
2. Inflammatory destruction of all or part of the extrahepatic bile ducts
3. Bile duct proliferation in the triads
4. Common indication for liver transplantation in a child

Front 136

What is primary sclerosing cholangitis? What is the genetic predisposition? Does it occur more in men or women?

Back 136

1) Obliterative fibrosis of intrahepatic and extrahepatic bile ducts
2) Association with HLA-DR52a (100%) and HLA-Cw7 (86%)
3) Male dominant (70%); usually <45 years old

Front 137

what other diseases is primary sclerosising cholangitis associated with?

Back 137

(1) Inflammatory bowel disease (70%)
a. Ulcerative colitis > Crohn's disease
(2) Other sclerosing disorders
a. Retroperitoneal and mediastinal sclerosing fibrosis

Front 138

What are complications of primary sclerosising cholangitis? How is PSC treated?

Back 138

(a) Cirrhosis
(b) Cholangiocarcinoma
Treatment:
1. Immunosuppressants
a.Corticosteroids
b. azathioprine
c. methotrexate
2. Invariably require a liver transplant

Front 139

Clinically how does someone with primary sclerosising cholangitis present?

Back 139

1. Jaundice
2. Pruritus
a. Deposition of bile salts/acids in skin
3. Hepatosplenomegaly

Front 140

What are some laboratory findings in primary sclerosising cholangitis?

Back 140

1. CB > 50%
2. Bilirubinuria
3. Absent urine UBG
4. Increase in serum ALP and GGT

Front 141

how is primary sclerosisng cholangitis diagnosed? what sign is seen?

Back 141

1. Endoscopic retrograde cholangiopancreatography (ERCP)
2. Dye study shows narrowing and dilation of bile ducts ("beading")

Front 142

angiosarcoma of the liver can be caused by?

Back 142

1) Vinyl chloride
2) arsenic
3) thorium dioxide (radioactive contrast material)

Front 143

cholangiosarcoma can result from what toxic exposure? Liver cell adenoma can result from what?

Back 143

1) Thorium dioxide, arsenic, vinyl chloride
2) oral contraceptives

Front 144

Hepatocellular carcinoma can occur from what toxic exposures?

Back 144

1) Vinyl chloride
2) aflatoxin (due to Aspergillus mold)

Front 145

Which drugs can cause acute hepatitis?

Back 145

1) Isoniazid (caused by toxic metabolite)
2) halothane
3) acetaminophen
4) methyldopa

Front 146

Cholestasis can result from what drugs?

Back 146

1) Oral contraceptive pills (estrogen interferes with intrahepatic bile secretion)
2) anabolic steroids (same mechanism as OCPs)

Front 147

Fatty liver can be induced by what drugs?

Back 147

1) Amiodarone (resembles alcoholic hepatitis; Mallory bodies and progression to cirrhosis)
2) methotrexate

Front 148

Liver fibrosis can result from what drugs?

Back 148

1) Methotrexate
2) retinoic acid
3) amiodarone

Front 149

A liver biopsy shows dilated bile ductules filled with yellowish-green bile. What could it be?

Back 149

cholestasis

Front 150

What is cirrhosis?

Back 150

Irreversible diffuse fibrosis of the liver with formation of regenerative nodules

Front 151

How are regenerative nodules in cirrhosis characterized? What do normal structures do they lack? What gets compressed?

Back 151

1. Hepatocyte reaction to injury
2. Lack normal liver architecture
a. Lack of portal triads and sinusoids
3. Surrounded by bands of fibrosis
4. Compress sinusoids and central veins
a. Intrasinusoidal hypertension
b. Reduction in the number of functional sinusoids
c. Increase in hydrostatic pressure in portal vein

Front 152

What are several causes of cirrhosis including autoimmune and metabolic causes?

Back 152

1. Alcoholic liver disease (most common)
2. Postnecrotic cirrhosis (HBV, HCV)
3. Autoimmune disease
a. Primary biliary cirrhosis
b. Autoimmune hepatitis
4. Metabolic diseases
a. Hemochromatosis
b. Wilson's disease
c. α1-Antitrypsin deficiency
d. Galactosemia

Front 153

Where is ammonia made? What happens to it in the body?

Back 153

1) Ammonia derives from metabolism of amino acids and from the release of ammonia from amino acids by bacterial ureases in the bowel
2) Ammonia (NH3) is diffusible and is reabsorbed into the portal vein for delivery to the urea cycle where it is metabolized into urea

Front 154

What are methods of reducing ammonia?

Back 154

1) Ammonium (NH4) is not reabsorbed in the bowel and is excreted in stool
2) Methods for reducing ammonia in the colon include restriction of protein intake (most cost effective) and the use of oral neomycin, which destroys the colonic bacteria
3) Oral administration of lactulose results in the release of hydrogen ions, causing NH3 to be converted to NH4, which is excreted in the feces.

Front 155

What is useful in distinguishing ascites of liver origin from ascites of peritoneal origin? How is it applied?

Back 155

1) Peritoneal fluid analysis
2) The gradient between serum albumin and ascitic fluid albumin (serum albumin - ascitic fluid albumin) is very helpful in making this distinction
3) A difference > 1.1 g/dL is ascites of liver origin, while a difference < 1.1 g/dL is of peritoneal origin (e.g., peritonitis)

Front 156

Is hepatic ascites or peritoneal ascites a transudat? Which is an exudate? How can they further be distinguished by the immune cells present?

Back 156

1) ascites of liver origin is a transudate, which is a protein-poor and cell-poor fluid
a. hence, the expected difference between serum albumin and ascitic albumin is increased.
2) ascitic fluid from peritonitis is an exudate, which is a protein-rich and cell-rich fluid
a. hence, the difference between serum and ascitic fluid is much less.
3) Peritoneal fluid protein concentration and cell count are also useful.
a. A total peritoneal fluid protein concentration < 2.5 g/dL and WBC count < 300 cells/mm3 + neutrophils < 25% of the total count is consistent with a transudate
b. a concentration > 2.5 g/dL and a WBC count > 300 cells/mm3 + neutrophils > 25% of the total count indicates an exudate.

Front 157

What are a few findings in hepatic failure?

Back 157

1) Multiple coagulation defects
a. Due to inability to synthesize coagulation factors
b. Produces a hemorrhagic diathesis
2) Hypoalbuminemia from decreased synthesis of albumin
a. Produces dependent pitting edema and ascites
3) hepatic encephalopathy
4) hepatorenal syndrome
5) ascites (caput medusa)

Front 158

Describe the pathogenesis of hepatic encephalopathy? is it reversible?

Back 158

(1) Reversible metabolic disorder
(2) Increase in aromatic amino acids (e.g., phenylalanine, tyrosine, tryptophan)
a. Converted into false neurotransmitters (e.g., γ-aminobutyric acid)
(3) Increase in serum ammonia
a. Due to a defective urea cycle that cannot metabolize ammonia
(4) Factors precipitating encephalopathy
a. Increased protein (most important)
b. Dietary or blood in gastrointestinal tract increases bacterial conversion of urea into ammonia
c. Alkalosis keeps ammonia in NH3 state
** Diuretics (loop and thiazide) produce metabolic alkalosis.
d. Sedatives
e. Portasystemic shunts
** Shunt ammonia away from the liver, which normally metabolizes ammonia in the urea cycle

Front 159

What are clinical complications of hepatic encephalopathy?

Back 159

(a) Alterations in the mental status
(b) Somnolence and disordered sleep rhythms
(c) Asterixis (i.e., inability to sustain posture, flapping tremor from inability to sustain a muscle contraction)
(d) Coma and death in late stages

Front 160

How does portal hypertension develop in liver cirrohosis?

Back 160

(1) Resistance to intrahepatic blood flow due to intrasinusoidal hypertension
(2) Anastomoses between portal vein tributaries and the arterial system

Front 161

What are complications of portal hypertension due to cirrhosis?

Back 161

(1) Ascites
(2) Congestive splenomegaly
a. Increased hydrostatic pressure in splenic vein
b. Hypersplenism with various cytopenias may occur
(3) Esophageal varices
(4) Hemorrhoids
(5) Periumbilical venous collaterals (caput medusae)

Front 162

What are some of the blood shunts used with pulmonary hypertension due to cirrhosis?

Back 162

(1) Portacaval shunt
a. Connects the portal vein with the vena cava
(2) Mesocaval shunt
a. Connects the superior mesenteric vein with the vena cava.
(3) Splenorenal
a. Most physiologic shunt
b. Connects the splenic vein with the renal vein
c. Reduces PH and bleeding from varices without bypassing the liver

Front 163

When is a Transjugular intrahepatic portosystemic shunt (TIPS) used? What is it? What does it increase risk of?

Back 163

(4) portal hypertension secondary to cirrhosis
a. Metal stent connects portal vein with hepatic vein.
b. Reduces portal vein pressure
c. Increases risk for encephalopathy
d. Used in treatment of acute esophageal bleeds
e. Used in treating patients awaiting liver transplantation

Front 164

Why might the splenorenal shunt in portal hypertension with cirrhosis be better than other shunts?

Back 164

1) does not bypass liver
a. most physiologic shunt
b. shunts that bypass the liver can precipitate encephalopathy

Front 165

What is the pathogenesis of ascites in cirrhosis?

Back 165

(1) Portal hypertension
a. Increase in portal vein hydrostatic pressure
(2) Hypoalbuminemia
a. Decreases oncotic pressure
(3) Secondary hyperaldosteronism causes:
a. Decreased cardiac output
b. Activates the renin-angiotensin-aldosterone system (retention of Na+ and water)
c. Liver is unable to metabolize aldosterone.

Front 166

Is ascites in cirrhosis a transudate or an exudate? why?

Back 166

1) transudate due to alterations in Starling pressures
a. secondary aldosteronism

Front 167

Describe hepatorenal syndrome? Is it reversible? what is creatinine clearance? what happens to renal tubular function?

Back 167

1) Reversible renal failure without renal parenchymal disease
a. Creatinine clearance < 40 mL/minute
2) Approximately 20% of people with hepatic failure die of this syndrome.
3) Absence of:
a. Shock
b. Volume depletion
c. Infection
d. Obstructive or parenchymal renal disease
4) Preservation of renal tubular function
a. Random urine Na+ < 20 mEq/L
b. Absence of significant proteinuria (<500 mg/day) or hematuria
c. ? Due to decreased renal blood flow
d. Serum blood urea nitrogen and creatinine are increased

Front 168

How is hepatorenal syndrome treated?

Back 168

(1) Supportive care including dialysis
(2) Vasopressin analogues
(3) Vasoconstrictors (e.g., norepinephrine, midodrine)
(4) Albumin for volume expansion
(5) Liver transplantation is the only curative treatment.
(6) Mortality rate > 80%

Front 169

why does hyperestrinism result in males with cirrhosis? what are clinical findings?

Back 169

Pathogenesis:
(1) Liver cannot degrade estrogen and 17-ketosteroids (e.g., androstenedione).
(2) Androstenedione is aromatized into estrogen in the adipose cells.
Clinical findings:
(1) Gynecomastia
(2) Spider telangiectasia
(3) Female distribution of hair
(4) palmer erythema (liver palms)

Front 170

What is postnecrotic cirrhosis due to? what is there increased risk of?

Back 170

1. Most often caused by chronic hepatitis due to HBV and HCV
2. Increased incidence of hepatocellular carcinoma
a. Incidence of which virus is most common varies around the world

Front 171

What are morphologic features of postnecrotic necrosis? What does an alcoholic liver look like?

Back 171

1) large irregular nodules divided by fibrous bands
2) alcoholic most often mirconodular separated by fibrous bands
a. nodules contain distorted liver plates

Front 172

What is primary biliary cirrhosis? What is it associated with? Who does it occur in? what does it progress to? what is there increased risk of?

Back 172

1. Granulomatous destruction of bile ducts in portal triads
2. Autoimmune disorder
a. Association with other autoimmune diseases (e.g., Sjögren's syndrome, RA, CREST, Celiacs)
3. Occurs in women (>90%) between 40 and 50 years of age
4. Progresses from a chronic inflammatory reaction to cirrhosis with pulmonary hypertension
5. Increased risk for hepatocellular carcinoma

Front 173

What is the pathogenesis of primary biliary cirrhosis? What antibody is present? do they reflect disease activity?

Back 173

1. ? Environmental insult affecting mitochondrial proteins triggering CD8 T-cell destruction of intralobular bile duct epithelium
2. Enzyme complex subunit in mitochondrial membrane is the autoantigen recognized by CD8 T cells
3. Autoantibodies (antimitochondrial antibodies) develop against the mitochondria
a. Do not correlate with disease activity

Front 174

Clinically how does primary biliary cirrhosis present? What sign is present before jaundice? What are late findings?

Back 174

1. Pruritus (20-70%)
a. Unknown etiology (not bile salts in skin)
b. Early finding well before jaundice appears
2. Painful hepatosplenomegaly
3. Jaundice (60%)
a. Late finding after most of the bile ducts have been destroyed
4. Inflammatory arthropathy (40-70%)
5. Xanthelasma (40%)
a. Late finding
b. Due to cholesterol in bile
6. Kayser-Fleischer ring in cornea
a. Due to retention of copper
b. parenchyma also has increased copper

Front 175

What are some laboratory findings in primary biliary cirrhosis?

Back 175

1. Antimitochondrial antibodies (AMA; >90%)
2. Serum ANA positive (50%)
3. Increase in serum IgM
4. Increased serum ALP and GGT
5. Increased serum cholesterol
a. Component of bile

Front 176

How is primary biliary cirrhosis treated?

Back 176

1. Budesonide + ursodeoxycholic acid
2. Cholestyramine for pruritus
3. Liver transplantation
a. Improves survival; 70% survive 10 years

Front 177

What are causes of secondary biliary cirrhosis? How is it seen histologocially?

Back 177

1. Complication of chronic extrahepatic bile duct obstruction
a. cystic fibrosis, where bile is dehydrated
b. ascending cholangitis and bacterial inflammation of intrahepatic bile ducts
2. No increase in serum AMA or IgM
3. histology shows bile stasis and bile lakes within hepatic parenchyma

Front 178

What gene is mutated in hereditary hemochromotosis? Which chromosome is it on? What is the proteins function? what happens with it in hereditary hemochromotosis?

Back 178

1) Hfe (autosomal recessive)
2) chromosome 6
3) The normal function of the HFE gene product is to facilitate the binding of plasma transferrin (binding protein of iron) with its mucosal cell transferrin receptor so that transferrin can be endocytosed by intestinal cells
4) The amount of endocytosed transferrin iron determines how much mucosal cell iron is released into the plasma
5) In hemochromatosis, when there is a mutated HFE gene, mucosal cell transfer of iron to plasma transferrin is always at a maximum resulting in iron overload

Front 179

What is hemosiderosis? What are causes?

Back 179

1) secondary hemochromatosis (acquired)
2) caused by multiple blood transfusions (e.g., sickle cell anemia, thalassemia major), alcohol abuse (alcohol increases iron reabsorption), and well water (iron pipes)
3) Iron deposits are more prevalent in macrophages than in parenchymal tissue.

Front 180

What are genetics of hereditary hemochromotosis? What is HLA is it associated with? Who is it most common in? when is the diagnosis in females as opposed to males made?

Back 180

1. Autosomal recessive disorder
a. Linked to short arm of chromosome 6
b. HLA-A3 association
2. Most common genetic disorder in North European ancestry
3. Male dominant disorder
a. Diagnosis usually made in fifth decade
4. In women, diagnosis usually made 10 to 20 years after menopause
a. Due to menses causing loss of iron

Front 181

What is the pathogenesis of hereditary hemochromotosis?

Back 181

1) Unrestricted reabsorption of iron in the small intestine
2) Mutations involving hereditary hemochromatosis gene (HFE)
a. Two missense mutations (C282Y and H63D)
b. There is a 1:10 carrier rate in the population.
3) Iron stimulates the production of hydroxyl free radicals
a. Free radicals damage tissue and cause fibrosis.

Front 182

In hereditary hemochromotosis?

Back 182

1) Liver (target organ)
2) pancreas
3) heart
4) joints
5) skin
6) pituitary

Front 183

Clinically what is seen in hereditary chromotosis? How are skin and joints effected?

Back 183

1. Cirrhosis (60%)
a. Iron deposits primarily in hepatocytes
b. Increased risk of hepatocellular carcinoma
2. "Bronze diabetes"
a. Type I diabetes mellitus (60%)
** Destruction of β-islet cells
b. Hyperpigmentation (75%)
** Iron deposits in skin and increases melanin production
3. Malabsorption
a. Destruction of exocrine pancreas
4. Restrictive cardiomyopathy
5. Hypogonadism
a. Amenorrhea in women (25%)
b. Testicular atrophy; loss of libido in men (50%)
6. Degenerative joint disease (>40%)
a. Chondrocalcinosis

Front 184

What are laboratory findings in hereditary chromotosis? What is serum ferritin primarily used for?

Back 184

1) Increased serum iron, percent saturation, and ferritin
a. Transferrin saturation is the best screening test.
b. Values > 45% indicate further evaluation is necessary.
c. Decreased total iron-binding capacity (TIBC)
d. Transferrin synthesis is decreased when iron stores are increased
(2) Serum ferritin is primarily used to follow therapy.

Front 185

What is seen histologically in hereditary chromatosis? What stain is used? Which sex hormones are primarily affected and decreased?

Back 185

1) pigment cirrhosis = micronodular cirrhosis with enormous accumulation of hemosiderin stained with PRUSSIAN blue
2) Decreased serum luteinizing hormone and follicle-stimulating hormone

Front 186

How is hereditary hemochromatosis screened? How is it treated? What is prognosis dependent on?

Back 186

1) Screening test for relatives
a. HFE gene testing for C282Y mutation
2) Treatment
a. Phlebotomy until serum ferritin < 50 μg/mL, saturation < 30%
b. Deferoxamine (iron chelator)
3) Normal life expectancy if no cirrhosis

Front 187

Wilsons disease is also known as?

Back 187

1) hepatolenticular degeneration
2)

Front 188

What is the normal role and function of ceruplasmin and albumin in Cu2+ and how is excreted?

Back 188

1) Ceruloplasmin is an enzyme that is synthesized in the liver.
a. It contains 6 atoms of copper in its structure.
2) Ceruloplasmin is secreted into the plasma where it represents 90% to 95% of the total serum copper concentration.
3) The remaining 5% to 10% of copper is free copper that is loosely bound to albumin.
4) Ceruloplasmin is eventually taken up and degraded by the liver.
5) The copper that was bound to ceruloplasmin is excreted into the bile.

Front 189

How does the defect in Wilson's disease affect Cu2+ regulation?

Back 189

1) The gene defect in Wilson's disease affects a copper transport system that produces a dual defect:
a. decreased incorporation of copper into ceruloplasmin in the liver
b. decreased excretion of copper into bile
2) Accumulation of copper in the liver increases the formation of hydroxyl free radicals causing damage to hepatocytes
3) Liver disease progresses from acute hepatitis to cirrhosis.

Front 190

What happens with/in a few years of someone having Wilson's disease?

Back 190

1) In a few years, unbound copper is released from the liver into the circulation (increased in blood and urine) where it damages the brain, kidneys, cornea, and other tissues.

Front 191

Who does Wilson's disease occur in? what are genetics? What does it progress to?

Back 191

1) Autosomal recessive disorder
2) Affects men and women equally
3) Onset of symptoms from 3 to 40 years of age
a. Usually late childhood
4) Liver disease progresses from acute hepatitis to cirrhosis

Front 192

what is pathogenesis of Wilson's disease?

Back 192

1. Gene mutation
a. Defective hepatocyte transport of copper into bile for excretion
b. Defective incorporation of copper into ceruloplasmin (binding protein for copper in blood)
2. Unbound copper eventually accumulates in blood.
a. Loosely attached to albumin
b. Copper deposits in other tissues cause a toxic effect.

Front 193

What are kayser-flescher rings? are they pathognomonic for Wilson's disease?

Back 193

1) Due to free copper deposits in Descemet's membrane in the cornea
2) Not pathognomonic of Wilson's disease
a. can be seen in primary biliary cirrhosis

Front 194

How is the CNS affected in Wilson's disease?

Back 194

(1) Copper deposits in the putamen
a. Produces a movement disorder resembling parkinsonism
(2) Copper deposits in the subthalamic nucleus
a. Produces hemiballismus
(3) Copper is toxic to neurons in the cerebral cortex
a. Produces dementia
(4) lenticular degeneration in CNS

Front 195

How does Wilson's disease affect liver, spleen, kidney and blood cells?

Back 195

1) Hepatosplenomegaly (50%)
a. Liver biopsy shows increased copper.
b. can be micro or macronodular
2) Hemolytic anemia
3) Renal disease
a. Proximal tubule damage produces Fanconi syndrome

Front 196

What are laboratory findings in Wilson's disease?

Back 196

1. Decreased total serum copper
a. Due to decreased ceruloplasmin
2. Decreased serum ceruloplasmin
a. Useful in diagnosing Wilson's disease in its early stages
3. Increased serum and urine free copper
a. Useful in diagnosing Wilson's disease in the later stages
4. aminoaciduria and glycosuria

Front 197

What is the Most common cause of cirrhosis in children? What are genetics? What are different defective allele types?

Back 197

1) alpha1-antitrypsin
2) Autosomal dominant (codominant)
3) Alleles are inherited codominantly (each allele expresses itself).
4) Normal allele is M (95% frequency in the United States).
a. MM is normal genotype with AAT in normal range.
5) Deficient variant (decreased AAT) Z allele (1-2% frequency)
6) Deficient variant (decreased AAT) S allele (2-3% frequency)

Front 198

What is the ZZ variant of AAT associated with?

Back 198

(5) Severe deficiency most commonly occurs in homozygous ZZ variant.
a. Decreased (<15% of normal) AAT levels in serum
b. Associated with panacinar emphysema
c. Associated with cirrhosis of the liver
d. Risk of lung disease in heterozygotes (e.g., MZ) is uncertain

Front 199

In ∼50% of homozygous ZZ patients what is not secreted properly? what stain can be used to determine? How does and what age does it present? What is there increased risk of?

Back 199

1) AAT is not secreted properly from hepatocytes
a. accumulates in hepatocyte ER
2) Pathologic accumulation of AAT in hepatocytes causes liver damage.
a. Periodic acid-Schiff stains show red cytoplasmic granules
2) Presents as neonatal hepatitis with intrahepatic cholestasis
3) Hepatitis progresses into cirrhosis.
a. AAT deficiency is the most common cause of cirrhosis in children.
4) Increased risk for hepatocellular carcinoma

Front 200

What are 10 potential abnormal lab findings in liver cirrhosis?

Back 200

1. Decreased serum blood urea nitrogen (BUN) and increased serum ammonia
2. Fasting hypoglycemia
3. Chronic respiratory alkalosis
a. Toxic products from hepatic dysfunction overstimulate respiratory center
4. Lactic acidosis
a. Liver dysfunction in converting lactic acid to pyruvate
5. Hyponatremia
a. Decreased cardiac output
b. Kidney reabsorbs slightly hypotonic solution (↑ TBNa+/↑↑ TBW)
6. Hypokalemia
a. Secondary aldosteronism increases renal exchange of Na+ for K+
7. Increased PT
8. Hypoalbuminemia
a. Decreased synthesis of albumin
9. Hypocalcemia
a. Hypoalbuminemia decreases the total serum calcium.
b. Approximately 40% of the total calcium is calcium bound to albumin.
c. Vitamin D deficiency
10. Mild transaminasemia
* Enzymes are not markedly increased due to the loss of parenchymal cells.

Front 201

on cut surface of liver a micronodular surface is seen with regenerative nodules are surrounded by collagen. What could this person have had?

Back 201

alcoholic cirrhosis earlier stages
Note: late stages can develop hobnail liver with larger and irregular nodules

Front 202

Person with pruritus has a Liver biopsy is stained with prussian blue and shows abundant blue staining material. what could person have?

Back 202

hereditary hemachromatosis

Front 203

What is focal nodular hyperplasia of liver? who is it more common in?

Back 203

1. Tumor-like condition
2. More common in women than men
3. Cause is unknown
a. Probable reaction to injury
4. Usually an incidental finding

Front 204

What are gross findings in focal nodular of liver? What is seen on CT? How is it treated?

Back 204

1. Poorly encapsulated nodule
2. Central depressed stellate scar
a. Contains large blood vessels
3. Fibrous septae radiate to the periphery.
4. CT scan:
a. Hypervascular mass with arteriovenous connections
5. Treatment
a. Leave it alone unless associated with pain

Front 205

What is the Most common benign tumor of the liver? What is a potential complication?

Back 205

1) Cavernous hemangioma
2) Rare cause of intraperitoneal hemorrhage

Front 206

Is hepatic adenoma benign or malignant? Does it occur more in men or women? What are causes?

Back 206

1) Benign tumor of hepatocytes
2) Occurs in women more often than men
3) Causes:
a. OCPs (most common)
b. Anabolic steroids
c. Von Gierke's glycogenosis

Front 207

How are hepatic cell adenomas characterized? what do they have a tendency to do? Will they go away?

Back 207

1) Highly vascular tumors
2) Tendency to rupture during pregnancy
3) Produce intraperitoneal hemorrhage
4) Tend to regress if off OCP and anabolics

Front 208

What is the most common cause of liver cancer? How is it characterized?

Back 208

1) metastasis
a. Primary cancers of lung (most common)
b. gastrointestinal tract
c. breast
2) Multiple nodular masses

Front 209

What is the Most common primary liver cancer? who does it occur more in? why are rates increasing in US?

Back 209

1) Hepatocellular carcinoma
2) Rapidly increasing in the United States due to increase in HCV infection
(3) Occurs in males more than females
a. Peaks around fifth and sixth decades

Front 210

What are several causes of hepatocellular carcinoma?

Back 210

(a) Postnecrotic cirrhosis due to chronic HBV and HCV
(b) Alcoholic cirrhosis
(c) Aflatoxins (from Aspergillus mold in grains and peanuts)
(d) Hereditary hemochromatosis, Wilson's disease
(e) PBC, AAT deficiency, tyrosinemia

Front 211

What are gross and microscopic findings of hepatocellular carcinoma?

Back 211

1) Gross findings
a. Focal, multifocal, or diffusely infiltrating cancer
** With or without pre-existing cirrhosis (usually with pre-existing cirrhosis)
b. Portal and hepatic vein invasion is common.
2) Microscopic findings
a. Characteristic finding is the presence of bile in neoplastic cells
Note: may lead to Budd-Chiari syndrome

Front 212

Clinically how do people with hepatocellular carcinoma present?

Back 212

(1) Over one third are asymptomatic.
(2) Abdominal pain is a common initial presentation.
(3) Fever
a. Due to liver cell necrosis
(4) Rapid enlargement of the liver in a patient with cirrhosis
a. Increased ascites; blood present in ascitic fluid
(5) polycythemia
(6) hypoglycemia

Front 213

What are serum markers in hepatocellular carcinoma? What ectopic hormones are released?

Back 213

(1) Increased α-fetoprotein (AFP; 70%)
a. Sensitivity 40% to 60%, specificity 80% to 94%
(2) Increased serum ALP and GGT
a. Sudden increase is a characteristic finding.
(3) Production of ectopic hormones
a. Erythropoietin (EPO; secondary polycythemia)
b. Insulin-like factor (hypoglycemia)
c. Parathyroid hormone (PTH)-related protein (hypercalcemia)

Front 214

Where does hepatocellular carcinoma primarily metastasize? What will angiography of liver show?

Back 214

1) lung
2) Angiography shows pooling and increased vascularity.

Front 215

How is hepatocellular carcinoma treated and what is prognosis?

Back 215

Treatment:
(1) Surgery (<20% are surgical candidates)
(2) Liver transplantation
(3) Radiation and chemotherapy are usually not helpful.
Prognosis
(1) If unresectable, most die within 6 months.
(2) If resectable, 5-year survival rate is 30% to 50%.

Front 216

What is the Most common cyst in biliary tract in children younger than 10 years old? How does it present? How is it diagnosed?

Back 216

1) choledochal cyst
2) Abdominal pain with persistent or intermittent jaundice
3) Increased incidence of cholelithiasis, cholangiocarcinoma, and cirrhosis
4) Ultrasound is screening test of choice
5) Endoscopic retrograde cholangiopancreatography (ERCP) or transhepatic cholangiography
a. Useful in identifying intra- and extrahepatic cysts
b. Useful in identifying sites of obstruction

Front 217

Is Caroli disease autosomal dominant or recessive? What happens in disease?

Back 217

1) Autosomal dominant and recessive types
2) Segmental dilatation of intrahepatic bile ducts
3) Portal tract fibrosis

Front 218

What is Caroli's disease associated with? what is there increased risk of?

Back 218

(1) Association with polycystic kidney disease
a. Autosomal recessive types in children or autosomal dominant in adults
(2) Increased incidence of cholangiocarcinoma
(3) Increased incidence of the following:
a. Intrahepatic cholelithiasis
b. cholangitis
c. hepatic abscesses
d. portal hypertension

Front 219

What is the Most common malignancy of bile ducts? What are causes?

Back 219

1) cholaniocarcinoma
2) Causes:
1. Primary sclerosing cholangitis
a. Most common cause in the United States
2. Clonorchis sinensis (Chinese liver fluke)
3. Thorotrast (thorium dioxide)
4. Choledochal cyst, Caroli disease

Front 220

Where are locations for cholangiocarcinoma?

Back 220

1. Ampulla or common bile duct (most common sites)
2. Junction of right/left hepatic duct (Klatskin tumor)
3. Intrahepatic

Front 221

What is a cholangiocarcinoma called if located at the Junction of right/left hepatic duct?

Back 221

klatskin tumor

Front 222

How is cholangocarcinoma similar to hepatocarcinoma? How is it different?

Back 222

Similar:
1) invades vascular channels
Unlike:
1) not associated with HBV or cirrhosis

Front 223

How does cholangocarcinoma present? What sign is positive?

Back 223

1. Obstructive jaundice
2. Palpable gallbladder (Courvoisier's sign)
a. Only mid-common bile duct or ampulla locations
3. Hepatomegaly

Front 224

How does estrogen lead to gallstone formation?

Back 224

1) Estrogen increases the synthesis of high-density lipoprotein (HDL)
a. transports cholesterol from peripheral tissue to the liver for excretion in bile
2) Estrogen also upregulates low-density lipoprotein (LDL) receptor synthesis in hepatocytes
3) increases HMG-CoA reductase activity, the rate-limiting enzyme in CH synthesis

Front 225

What are the components of bile?

Back 225

1. Bile salts/acids (∼67%)
a. Hepatic product of cholesterol (CH) metabolism
b. Water soluble
c. Detergent action renders CH soluble in bile.
2. Phospholipid (22%)
a. Mainly lecithin
b. Hydrophobic
c. Solubilizes CH in bile
3. Protein (4.5%), free CH (4%), conjugated bilirubin (0.3%)
4. Water, electrolytes, bicarbonate

Front 226

What are characteristics of cholesterol stones? are they radio-opaque?

Back 226

(1) Usually stones are of mixed composition.
(2) Stones contain CH, calcium carbonate, some bilirubin pigment.
a. Can be radiopaque if they contain calcium carbonate
(3) Rarely are stones purely CH.
(4) CH stones are radiolucent.

Front 227

What are black pigment gallstones a sign of?

Back 227

(a) Sign of chronic extravascular hemolytic anemia
a. Examples-sickle cell anemia, hereditary spherocytosis
(b) Excess bilirubin in bile produces calcium bilirubinate

Front 228

What are brown pigment stones a sign of? Who do they occur in?

Back 228

(a) Sign of infection in the common bile duct (CBD)
(b) Commonly seen in Asians

Front 229

How do cholesterol stones form?

Back 229

(1) Supersaturation of bile with cholesterol
(2) Decreased bile salts/acids and lecithin
a. Both normally solubilize cholesterol in bile

Front 230

What are risk factors for cholesterol gallstones?

Back 230

(a) Female > 40 years old
(b) Obesity
** Cholesterol is increased in bile.
(c) Use of oral contraceptive pills
(d) Rapid weight loss; use of lipid-lowering drugs
(e) Native Americans (e.g., Pima and Navajo Indians)
Note: female, fat, forty, fertile
(f) Crohns
(g) CF

Front 231

What are complications of gallstones?

Back 231

1. Cholecystitis (most common)
2. CBD obstruction
3. Gallbladder cancer
4. Acute pancreatitis
5. biliary colic
6. jaundice
7. gallstone ileus = intestinal obstruction from passage of large gallstone through eroded gallbladder into adjacent small bowel
8. mucocele = distended mucus filled gallbladder

Front 232

Who does acute cholecystitis commonly occur in?

Back 232

1. More common in women than in men
2. Occurs most often during fifth and sixth decades
3. High incidence in Native Americans (see above)
4. Associated with gallstones in >95% of cases

Front 233

What occurs in stage 1 of acute cholecystitis?

Back 233

(1) Stone lodges in the cystic duct
a. Stimulus of food causes gallbladder (GB) contraction.
b. Stone is forced into the cystic duct.
(2) Midepigastric colicky pain occurs.
a. Due to GB contraction against obstructed cystic duct
(3) Nausea and vomiting without pain relief

Front 234

What occurs in stage 2 of acute cholecystitis? What bacteria are present?

Back 234

(1) Stone becomes impacted in the cystic duct.
(2) Mucus accumulates behind the obstruction.
(3) Chemical irritation of mucosa
(4) Bacterial overgrowth (no invasion)
a. Most commonly Escherichia coli
b. Less commonly-Enterococci, Bacteroides fragilis, Clostridium sp
(5) Pain shifts to right upper quadrant (RUQ)
a. Dull, continuous aching pain
b. Pain radiation to right scapular/shoulder

Front 235

What occurs in stage 3 of acute cholecystitis?

Back 235

(1) Bacterial invasion of GB wall
(2) Localized peritonitis with rebound tenderness
(3) Positive Murphy sign
(4) Absolute neutrophilic leukocytosis
(5) Attack subsides if the stone falls out of the cystic duct
a. Approximately 90% subside over 37 days
b. If not, it perforates (next stage)

Front 236

What occurs in stage 4 of acute cholecystitis?

Back 236

(1) Perforation
a. Wall tension from GB distention compresses lumens of intramural vessels → gangrenous necrosis

Front 237

What infections in HIV can cause acute cholecystitis?

Back 237

Infection with cytomegalovirus (CMV) or Cryptosporidium

Front 238

Physical exam shows what in someone with acute cholecystitis?

Back 238

1. Fever
2. See stages of acute cholecystitis
3. Vomiting (75%)
4. Radiation of pain to the right scapula/shoulder
5. Murphy sign
* Pain when the GB hits the examiner's finger on patient inspiration
6. Jaundice (25%)
a. Usually indicates CBD stone
b. Indication for CBD exploration
7. Palpable gallbladder (15%)

Front 239

What does blood work show in someone with acute cholecystitis?

Back 239

1. Absolute neutrophilic leukocytosis with left shift
a. WBC counts > 12,000 cells/mm3 (>70%)
2. Increased serum AST/ALP
3. Increased serum amylase suggests associated pancreatitis
4. Increased serum bilirubin > 4 mg/dL unusual
b. Usually indicates stone in CBD

Front 240

Is ultrasound a good test for acute cholecystitis?

Back 240

(1) Gold standard test (>98% sensitivity)
(2) Detects stones > 12 mm in diameter
(3) Detects sludge; evaluates GB wall thickness
(4) Not effective in identifying CBD stones (<30% sensitivity)

Front 241

With a acute cholecystitis what are indications to surgically explore the cystic bile duct for pathology?

Back 241

1. Jaundice
2. CBD dilatation > 12 mm
3. No stones in GB
4. Acute pancreatitis

Front 242

What are pain management drugs used in acute cholecystitis? Which are contraindicated? What antibacterials are used?

Back 242

1) Meperidine for pain
a. Do not use morphine
b. Contracts the sphincter of Oddi and worsens pain
2) Piperacillin-tazobactam

Front 243

How does someone with chronic cholecystitis present?

Back 243

1. Severe, persistent pain 12 hours postprandially in the evening
2. Pain radiates into the right scapular area.
3. Recurrent epigastric distress, belching, and bloating

Front 244

What is cholesterolosis? What else is it called? What is seen on gross exam?

Back 244

1. Excess cholesterol in bile (strawberry gallbladder)
a. Cholesterol deposits in macrophages
b. Produces a yellow, speckled mucosal surface
2. No clinical significance

Front 245

Who does gallbladder adenocarcinoma occur in? What is prognosis?

Back 245

1. Dominant in elderly women
2. Poor prognosis

Front 246

Pathologically what occurs in adenocarinoma? What is primary cause? what will it progress to?

Back 246

1) Cholelithiasis (95% of cases)
2) Porcelain gallbladder
a. Gallbladder with dystrophic calcification
b. Mandatory removal of GB
3) Approximately 50% risk for progression to cancer
a. Immediate surgical removal is warranted

Front 247

Someone has been diagnosed with a porcelin gallbladder what is prognosis? Why?

Back 247

1. Majority have already locally invaded liver or porta hepatis at discovery.
2. Five-year survival rate < 2%

Front 248

What happens with an annular pancreas?

Back 248

1. Dorsal and ventral buds form a ring around the duodenum.
2. Associated with small bowel obstruction

Front 249

How can the major pancreatic duct become obstructed? What does this lead to?

Back 249

1. Major pancreatic duct and CBD are confluent in their terminal part.
a. Both empty their contents into the duodenum via the ampulla of Vater.
2. Important in the pathogenesis of acute pancreatitis
a. Stone(s) obstruct terminal part of the CBD →
b. Increased back-pressure refluxes bile into the major pancreatic duct →
c/.Bile activates pancreatic proenzymes causing acute pancreatitis

Front 250

What is Courvosiers law?

Back 250

1) in the presence of an enlarged gall bladder which is nontender and accompanied with jaundice, the cause is unlikely to be gallstones
2) tumors that obstruct common bile duct result in enlarged gallbladder but obstructing stones do not

Front 251

What is third space fluid? How does it relate to the pancreas?

Back 251

1) Third space fluid is sequestered fluid that is unavailable for maintenance of volume in the vascular compartment (nonfunctional extracellular fluid).
2) In acute pancreatitis, it refers to the peripancreatic collection of fluid that commonly occurs as the pancreas autodigests itself.
3) If conditions improve, the third space fluid gains entry back into the vascular compartment and may cause fluid overload.

Front 252

Does chronic pancreatitis occur more in men or women? What are known causes?

Back 252

1. Occurs in men more commonly than women
2. Majority are idiopathic.
3. Known causes
a. Alcohol abuse is the most common known cause.
b. Cystic fibrosis is the most common cause in children.
c. Malnutrition is the most common cause in developing countries.
d. Autoimmune

Front 253

Pathologically what occurs in chronic pancreatitis? what radiographic sign is seen?

Back 253

1. Repeated attacks of acute pancreatitis produce duct obstruction.
2. Calcified concretions occur as well as dilation of the ducts.
a. Radiographic dyes show a "chain of lakes" appearance in the major duct.

Front 254

Clinically how do people with chronic pancreatitis present?

Back 254

1. Severe pain radiating into the back
2. Malabsorption
a. Indicates >90% exocrine function destroyed
3. Type 1 diabetes mellitus (70%)
a. Brittle diabetes due to loss of insulin and glucagon
4. Pancreatic pseudocyst

Front 255

What serum proteins are increased in chronic pancreatitis? Which are not reliable?

Back 255

1) Increased amylase and lipase (neither are reliable)
2) Increased serum immunoreactive trypsin

Front 256

What are tests for pancreatic sufficiency?

Back 256

(1) CT scan of pancreas shows dystrophic calcification
. Sign of chronic pancreatitis
(2) Functional tests:
a. Secretin stimulation test (requires instrumentation)
b.+ Tests ability of pancreas to secrete fluids and electrolytes
c. Bentiromide test
d. + Tests ability of pancreatic chymotrypsin to cleave orally administered bentiromide to para-aminobenzoic acid (measured in urine)

Front 257

How is chronic pancreatitis treated? what is prognosis?

Back 257

1. Abstain from alcohol.
2. Addiction is common.
a. Try simple analgesics or NSAIDs
3. Pancreatic enzymes
4. Fat-soluble vitamins
5. Octreotide for pain if idiopathic
6. Approximately 50% of patients die within 10 years.

Front 258

What is Whipples procedure?

Back 258

1) an en bloc resection of the pancreatic head and neck (distal pancreas remains to prevent diabetes mellitus) and resection of part of the CBD.
2) In some cases, there is resection of the antrum with vagotomy.

Front 259

Who does exocrine pancreatic cancer occur in? When?

Back 259

1) Slightly more common in men than women
2) Incidence rate is stable in men and women.
3) Usually occurs in seventh and eighth decades of life
4) Adenocarcinoma with varying degrees of differentiation

Front 260

What are causes of exocrine pancreatic cancer?

Back 260

(1) Smoking (most common cause)
a. Includes smokeless tobacco
(2) Chronic pancreatitis
(3) Hereditary pancreatitis
(4) Diabetes mellitus
a. Particularly in women
(5) High saturated fat diet; obesity; cirrhosis
Note: not associated with ALCOHOL

Front 261

What genes are associated with exocrine pancreatic cancer?

Back 261

1. Association with K-RAS gene mutation
2. Mutation of suppressor genes (TP16 and TP53)

Front 262

Where do most exocrine pancreatic tumors occur?

Back 262

1. Most occur in the pancreatic head (65% of cases)
a. Often blocks CBD causing jaundice
2. Remainder occur in the body and tail.

Front 263

Clinically how does exocrine pancreatic cancer present? where does it metastisize? What serum marker is elevated?

Back 263

1) Epigastric pain with weight loss (>90%)
2) Signs of CBD obstruction (carcinoma of head of pancreas)
a, Jaundice (>90%; CB > 50%)
b. Light-colored stools (absent UBG)
c. Palpable gallbladder (Courvoisier's sign; 30%)
3) Superficial migratory thrombophlebitis
4) Metastasis to left supraclavicular node (Virchow's node)
a. Also occurs in stomach cancer
5) Periumbilical metastasis (Sister Mary Joseph's sign)
a. Also occurs in stomach cancer
6) Increased CA19-9 and CEA

Front 264

What is Grey-Turner sign? what is it seen with?

Back 264

purplish discoloration in the loins due to tracking of hemorrhagic necrotic pancreatic material along the retroperitoneal planes

Front 265

What is Cullens sign? When is it seen?

Back 265

1) hemorrhagic discoloration around the umbilicus.
2) It is due to tracking of hemorrhagic necrotic pancreatic tissue around the falciform and umbilical ligaments

Front 266

Someone is admitted to ER with acute pancreatitis within first 24 hours. What are lab findings?

Back 266

1) age > 55 years old
2) WBC count > 16,000 cells/mm3
3) serum glucose > 200 mg/dL
4) serum LDH > 350 IU/L
5) serum AST > 250 U/L

Front 267

48 hours after the initial 24 hours of someone with acute pancreatitis what is seen?

Back 267

1) hematocrit drop > 10% with hydration
2) serum BUN rise > 5 mg/dL
3) Pao2 < 60 mm Hg (respiratory failure)
4) base deficit > 4 mEq/L (metabolic acidosis)
5) calcium < 8 mg/dL
6) fluid sequestration > 6 L

Front 268

What is the prognosis of acute pancreatitis based on number of presenting signs?

Back 268

1) <3 signs = 0.9% mortality rate
2) 3-4 signs = 11% to 16% mortality rate
3) 5-6 signs = 33 to 40% mortality rate
4) >6 signs = 100% mortality rate.

Front 269

What are ways in which pancreatic proenzymes become activated and lead to acute pancreatitis?

Back 269

1) Mechanisms of activation of proenzymes
a. Obstruction of the main pancreatic duct or terminal CBD
b. Gallstones
c. Alcohol thickens ductal secretions and increases duct permeability to enzymes
d. Chemical injury of acinar cells
**Examples-thiazides, alcohol, triglyceride (>1000 mg/dL)
e. Infectious injury of acinar cells
** Examples-CMV, mumps, coxsackievirus
f. Mechanical injury of acinar cells
** Examples-seat belt trauma, posterior penetration of duodenal ulcer
g. Metabolic activation of proenzymes (e.g., hypercalcemia, ischemia, shock)

Front 270

What is a very important enzyme for activating pancreatic proenzymes? How does pathogenesis proceed?

Back 270

1) Trypsin is important in the activation of proenzymes.
a. Proteases damage acinar cell structure.
b. Lipases and phospholipases produce enzymatic fat necrosis.
c. Elastases damage vessel walls and produce hemorrhage
d. Activated enzymes also circulate in the blood

Front 271

Clinically how does someone with acute pancreatitis present?

Back 271

1) Fever, nausea, and vomiting
2) Severe, boring (knife-like) midepigastric pain with radiation into the back
3) Hypovolemic shock
4) Hypoxemia
5) Grey-Turner sign (flank hemorrhage)
6) Cullen's sign (periumbilical hemorrhage)
7) Disseminated intravascular coagulation
a. Due to activation of prothrombin by trypsin
8) Tetany

Front 272

Why is there a pain in the back with acute pancreatitis? Why is there hypovolemic shock?

Back 272

1) Radiation into back is due to its retroperitoneal location.
2) Due to third space loss of fluids

Front 273

why is there hypoxemia in acute pancreatitis?

Back 273

(1) Circulating pancreatic phospholipase destroys surfactant.
a. Loss of surfactant produces atelectasis and intrapulmonary shunting.
(2) Acute respiratory distress syndrome (ARDS) may occur.

Front 274

Why is there DIC in acute pancreatitis?

Back 274

1) Due to activation of prothrombin by trypsin
2) Tetany
a. Hypocalcemia is caused by enzymatic fat necrosis.
b. Calcium binds to fatty acids leading to a decrease in ionized calcium

Front 275

Pancreatic necrosis can occur with acute pancreatitis. How does it present?

Back 275

(1) Systemic signs occur earlier than usual.
(2) Higher fever than usual; sinus tachycardia
(3) Greater degree of neutrophilic leukocytosis
(4) Peripancreatic infections occur in 40% to 70% of cases.

Front 276

A pancreatic pseudocyst is a complication of acute pancreatitis. what is it? How is it detected?

Back 276

(1) Collection of digested pancreatic tissue around pancreas
(2) Abdominal mass with persistence of serum amylase longer than 10 days
a. Amount of amylase in the fluid surpasses renal clearance of amylase

Front 277

What are lab and clinical findings of a pancreatic abscess a complication of acute pancreatitis?

Back 277

(a) Abdominal pain
(b) High fever due to sepsis
** Usually gram-negative infections such as E. coli or Pseudomonas spp.
(c) Neutrophilic leukocytosis
(d) Persistent hyperamylasemia

Front 278

How is a pancreatic abscess diagnosed?

Back 278

(a) CT scan shows multiple radiolucent bubbles in the retroperitoneum

Front 279

What usually causes pancreatic ascites? How is it detected?

Back 279

(1) Usually caused by leaking of a pseudocyst
(2) Peritoneal fluid has high amylase level.
(3) Usually resolves spontaneously