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Metabolic Liver disease Flashcards

1
Q

How should you diagnose NASH?

A

ultrasound/CT for steatosis

-exclusion of EtOH and other liver diseases

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2
Q

Mutation in hemachromatosis? How is it inherited?

A

Mutation =C282Y in HFE gene OR H63D. Autosomal recessive

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3
Q

Describe the pathophysiology behind hemachromatosis

A
  1. Decreased hepcidin activity
  2. Hepcidin cannot bind transportin
  3. high levels of transportin=extrusion of iron out of macrophages and enterocytes
  4. Increased GI absorption of iron which deposits into organs
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4
Q

At what age do you typically see hematchromatosis?

A
  1. Middle aged

2. Juvenile form

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5
Q

What labs would you see in HH?

A
  1. transferrin saturation > 45%

2. High ferritin

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6
Q

What do you see in histology of HH?

A
  1. High hepatic iron concentration–prussian blue stain will show iron
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7
Q

What is the gene involved in wilson’s disease?

A

ATP7B

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8
Q

What is the pathophysiology of wilson’s?

A

Less Cu-transporting ATPase. –>less Cu being pumped into the golgi
–Less Cu being packaged for excretion

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9
Q

What protein is cu bound to for secretion into the plasma?

A

Ceruloplasmin

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10
Q

When does wilson’s disease present?

A

can be child or adult.
CHILD: Liver dz
ADULT: liver dz plus neuropsych symptoms usually

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11
Q

What lab findings would you see in Wilson’s?

A

Low ceruloplasmin
Increased urinary copper
KF rings

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12
Q

What do you see on liver histology in wilsons?

A

Silver stain for copper is positive

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13
Q

What mutation do you have in alpha 1 AT?

A

Mutation in A1AT (ZZ, ZS alleles abnormal). MM is normal

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14
Q

How does a1AT deficiency actually cause disease?

A

Mutated A1AT accumulates in the liver

–Destruction of pulmonary CT matrix=interstitial lung dz

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15
Q

At what age does alpha 1 antitrypsin present?

A

Children or adults:
CHILD: more liver problems
ADULT: More pulmonary issues

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16
Q

What gene is responsible for A1AT protein?

A

SERPINA 1–results in a mutation of glutamine to lysine @ position 342

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17
Q

What is the normal role of A1AT?

A

inhibits proteases. Especially the damaging elastase produced by neutrophils

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18
Q

How can you diagnose A1AT?

A
  1. protein phenotyping or genotyping
  2. Low serum A1AT
  3. Liver biopsy
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19
Q

What can you see on biopsy of A1AT?

A

PAS positive globules (hot pink)

20
Q

Treatment for A1AT?

A
  1. smoking cessation
  2. Consider liver transplantation
  3. Can also provide an A1AT analogue to the lungs
21
Q

If you are deficient in A1AT, what other protease inhibitors might you be missing?

A
  1. C1 inhibitor
  2. Antithrombin III
  3. A1-antichymotrypsin
22
Q

Where is most of the body’s iron stored?

A

In macrophages and hepatocytes

23
Q

When might you have physiologically elevated levels of hepcidin?

A

During inflammation. It’s an acute phase reactant

24
Q

What does ferroportin do?

A

Main iron export protein. It’s found on enterocytes, hepatocytes, and macrophages.

25
Q

What does the HFE protein do?

A

It’s a sensor of circulating iron that’s found on hepatocytes

26
Q

What does Hepcidin do?

A

It regulates the amount of ferroportin in cells. It does this by binding to ferroportin and degrading it.

27
Q

Describe the pathway of iron absorption and storage starting with iron absorption in the gut

A
  1. Iron absorbed in intestine
  2. Excreted into blood through ferroportin on basolateral side
  3. Binds to apotransferrin in blood
  4. Absorbed by macrophages
28
Q

Describe the pathway for iron homeostasis

A
  1. Iron levels sensed in blood by HFE on hepatocytes and kupffer cells
  2. Hepcidin synthesized
  3. Enterocytes decrease Fe absorption
  4. Macrophages decrease iron export
  5. Plasma Fe drops
29
Q

When you have low hepcidin

A

Increase iron absorption nad deposition occurs.

30
Q

How does HFE mutation result in HH?

A

HFE is a sensor of iron levels. Without it, hepcidin cannot be synthesized, causing high ferroportin and lots of iron export

31
Q

Aside from HFE, what other mutations can lead to HH?

A

HJV, HAMP, TfR2 of a gain of function in ferroportin

32
Q

What is different about non-HFE iron overload?

A

It’s NOT associated with hepcidin function or level. Transferrin saturation is not high

  • –Iron in RES
  • -Not responsive to phlebotomy
33
Q

Examples of non-hemachromatotic iron overload dzs

A

Feroportin loss of function

  • Aceruloplasminemia
    3. Atransferrinemia
34
Q

Where does iron deposit in HH?

A

liver, heart, spleen, endocrine organs

35
Q

If you are a patient with HH, what is the most likely cause of death?

A

HCC
Cirrhosis
–Less so cardiomyopathy or diabetes

36
Q

A C282Y mutation (homozyg) puts you at increased risk of:

A

HCC and CRC

37
Q

A H62D mutation (homozyg) puts you at increased risk of:

A

HNPCC

38
Q

What levels of iron do you want to aim for in HH?

A

50-100 Ig/L

39
Q

What is the main transporter of Cu in the blood?

A

Ceruloplasmin

40
Q

What does the ATP7B protein do?

A

Chaperones Cu from the cytoplasm to the golgi apparatus for secretion. Without it, Cu stays in the cytoplasm and can’t be excreted in the bile.

41
Q

If you make a diagnosis of wilson’s…what follow up exam must you do?

A

Mandatory slit lamp eye exam for Kayser-Fleischer rings.

42
Q

Are Kayser-Fleischer rings specific to Wilson’s?

A

NO–>Can also see it generally in liver disease

43
Q

What do you see on histology of wilson’s disease?

A

Copper staining hepatocytes

  • -cirrhosis
  • steatosis
  • -mitochondrial abnormalities
44
Q

What is the clinical presentation of someone with wilson’s?

A

Pretty variable:

  1. Liver failure
  2. Renal dysfunction
  3. Cardiac problems
  4. CNS issues
  5. Kayser Fleischer rings
  6. Hemolytic anemia
45
Q

How do you treat wilsons?

A
  1. D-penicillamine (an iron chelator)

2. Trientine and zinc

GI (27 decks)

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