CM- Jaundice and Cholestasis Flashcards Preview

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Flashcards in CM- Jaundice and Cholestasis Deck (45):
1

What are the major components of bile?

Bile acids, bile salts, and biliary acids.
Bilirubin is only a MINOR component of bile

2

What are the 4 main EXOCRINE functions of the liver?

1. synthesize and secrete bile acids to digest fat/fat soluble vitamins
2. Metabolize and excrete bilirubin
3. transform and excrete drugs and toxins
4. metabolize and excrete lipids

3

What happens to bilirubin when it enters the hepatocyte?

It is conjugated by glucuronidation. The conjugated bilirubin is pushed out the bile canaliculi and a little bit goes back into the blood

4

What is the polarity and lipid solubility of bilirubin before it is conjugated in the hepatocyte?

it is non-polar and lipid soluble.

5

What is a situation where DB and TB are elevated and the other liver enzymes are not elevated?

Dubin-Johnson an Roder syndrome

6

Unconjugated hyperbilirubinemia can occur from increased __________ or decreased ____________.

Increased hemolysis or decreased output into bile (conjugation defect)

7

CB increased along with unconjugated in which situations?

1. transporter defect from the hepatocyte to the bile canaliculi
2. back flux of bilirubin from hepatic AND biliary disease

8

What level of bilirubin in circulation is associated with jaundice?

2-3mg/dL

9

What are the 3 situations that cause isolated increase in bilirubin?

1. hemolysis (prehepatic)

Hepatic:
2. defective conjugation (common, genetic)
3. impaired excretion into bile (rare, genetic)

10

What are causes of hyperbilirubinemia when it is accompanied by other lab abnormalities?

1. acute/chronic hepatitis
2. cholestatic and infiltrative liver disease
3. biliary tract obstruction

11

What are the UCB and CB levels in hemolysis?

UCB- increased
CB - normal

12

What are the UCB and CB levels in Gilbert's syndrome?
What causes this disorder?
What conditions exacerbate ?
What is the similar yet more severe disorder?

UCB- high
CB- low/normal - due to conjugation defect in hepatocyte

AD promotor defect in glucuronyl transferase

It is exacerbated by stress

Crigler-Najjar is the more severe disorder

13

What are the levels of CB and UCB in Dubin-Johnson?

CB is increased with TB because conjugation is fine but the bilirubin is not excreted into the bile canaliculi

14

Why does sepsis cause hyperbilirubinemia?

cytokines decrease transporter genes on the apical side of the hepatocyte so CB cannot enter the bile canaliculi
It also increases transporters on basolateral side so CB can enter the blood

15

What happens to the haptoglobin level with intravascular hemolysis?

It is decreased because it binds to bilirubin

16

What two tests are helpful to determine if hyperbilirubinemia is pure UCB or mixed?

1. Bilirubin fractionation - measure TB and CB and calculate UCB

2. Test for bilirubin in urine. It will be positive if CB is elevated.

17

In what two situations are hyperbilirubinemia NOT benign?

1. Infants after 2 wks b/c may be a sign of biliary atresia
2. rare patients with conjugation defects

18

What are the endocrine functions of the liver? What LFTs measure this?

Synthesize plasma proteins except immunoglobulins
Synthesize clotting factors except 8

LFTs are:
1. total protein
2. PT
3. Albumin

19

What 2 vitamins are stored in the liver?

A and B12

20

What LFTs actually access injury and inflammation?
Which is more specific for liver injury?

AST- mitochondria
ALT- cytosol

ALT is more specific because AST is released with cardiac, hemolysis, other tissue

alk phosphatase
GGT

21

Where are alk phos and GGT expressed?
When are they released?

They are in the biliary canalicular surface and are released when bile ducts are blocked

22

What are the pathological signs of apoptosis and necrosis of hepatocytes?

Apoptosis- Councilman bodies
Necrosis- balloon degeneration

23

When the aminotransferase level is above 500, what are the potential causes?

1. Viruses
2. Ischemia
3. Drugs and Toxins
4. Autoimmune (Host T lymphocytes)
5. Obstructive

24

In apoptosis, _________ are preferentially released. In necrosis ____________ are released.

1. aminotransferases
2. all enzymes

25

Where is ischemic injury first noted?

Centrilobular because it is last to receive blood supply

26

A patient has just traveled to Guatemala and has come in for a check up. Blood work shows AST>500. What is the likely cause?

Virus

27

A patient has just started a new drug and has AST>500. What is the likely cause?

Drug

28

A patient has been using cocaine. Now they have AST >500. What is the likely cause?

Ischemia

29

It is summer and a hyperthermic homeless man comes in. His AST>500. What is the likely cause?

Ischemia

30

A person comes in with dyspnea and shortness of breath. They have heart failure. AST >500. What is the likely cause?

Ischemia

31

A person presents with RUQ pain and an AST >500. What is the likely cause?

obstruction

32

In what 3 situations would you see LD or LDH elevation?

1. necrosis from ischemia
2. choledolithiasis
3. acetaminophen toxicity

33

what is the relationship between jaundice and cholestasis?

They can each occur separately but there is a lot of overlap.
Jaundice- icterus/elevated bilibubin
Cholestasis = obstruction in the biliary system/elevated alk phos

Ex. of J without C = hemolysis, genetic conjugation disorders

Ex. of C without J = biliary obstruction that is incomplete so enough bile is able to keep serum bilirubin below 2-3mg/dL

34

A patient presents with jaundice,pruritis, steattorrhea. They have trouble driving at night and are bleeding very easily. What is the most likely problem?
What will be increased in the serum?

Cholestasis

Elevated:
1. bile acids
2. abnormal lipoprotein
3. lipoprotein X
4. bilirubin (CB and UCB) if complete obstruction, infiltrate, or severe liver disease

35

What are the 3 major symptoms of cholestasis?

1. pruritus
2. steatorrhea from lack of bile salt
3. fat soluble vitamin deficiency from lack of bile salts

36

A patient presents with bleeding diathesis. What vitamin are they lacking? What is the likely problem?

Lacking vitamin K due to cholestasis

37

In cholestasis there is a lack of bile salts which cause deficiency of fat soluble vitamins. What are the 4 main fat soluble vitamins? What would be the major presenting symptom for each?

A- night blindness
D- osteomalacia
E- neuro deficit
K- bleeding

38

What causes intracellular cholestasis?

Disorders that interefere with the secretion into the bile canaliculus specifically:
hormones
drugs

39

What are causes of intrahepatic cholestasis?

Anything that obstructs or destroys bile ducts in the liver. For example:
1. schistosoma
2. sarcoid granulomas
3. portal fibrosis
4. PBC

40

What are examples of things that can cause extrahepatic cholestasis?

1. benign strictures
2. tumors of bile duct (cholangiocarcinoma)
3. pancreatic tumors

41

What is the most cost-efficient/first imaging study used when stomes are suspected?

Ultrasound

42

What is cholangiography? When is it used?

PTC: It is X-ray of the liver and bile duct after the injection of contrast to see if there is blockage in the bile duct
ERCP- injection of contrast into the common bile duct to see if there is obstruction in the pancreas or biliary tree

It is used if you need to delineate the precise nature of an obstruction

43

When extrahepatic causes of cholestasis have been ruled out, what is the next lab test you should do?

Liver biopsy because there may be an intrahepatic cause like:
1. PBC
2. sarcoid granuloma
3. portal fibrosis
4. schistosoma

44

What is the disorder if there is positive AMA?

PBC

45

What is the disorder if there is pANCA and cholestasis?

primary sclerosing cholangitis