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Gastrointestinal > Pathology Of The Liver And Biliary Tract 2 > Flashcards

Pathology Of The Liver And Biliary Tract 2 Flashcards

1
Q

What are the two major functions of hepatic bile?

A

1) emulsification of dietary fat in the lumen of the gut via bile salts
2) elimination of bilirubin, excess cholesterol and other waste products that cant be excreted into urine

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2
Q

Jaundice

A

Occurs when there is increased bilirubin production

- red cell hemolysis, hepatocyte dysfunctions, obstruction of bile flow are the big three causes

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3
Q

4 major steps of metabolism of bilirubin

A

1) uptake from the circulation
2) intracellular storage
3) conjugation with glucuronic acid
4) biliary excretion
* is end of product of heme degredation

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4
Q

How is most of the bilirubin-glucuronide complexes formed in the liver deconjugated?

A

Via gut lumen bacterial B-glucuronidases

- produces urobilinogens which are excreted in feces

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5
Q

What are the two primary human bile acids?

A

Glycocholic acid and taurocholic acid

- formed by glycine and taurine molecules (similar to bile salts as well)

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6
Q

What percentage of bile acids are reabsorbed?

A

95% via the hepatic portal vein into the enterohepatic circulation

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7
Q

What happens with unconjugated bilirubin?

A

It is insoluble and bound to plasma albumin
- required to have a small amount in the plasma in order to act as a free anion

  • if these levels rise, can cause toxic injuries due to diffusion into tissues*
  • these levels are seen in severe hemolytic disease, protein-binding drugs

if unconjugated bilirubin builds up in infants and diffuses Into the brain, it produces “kernicterus” which is severe jaundice and brain damage due to bilirubin build up

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8
Q

Normal serum bilirubin levels are what?

A
  1. 3-1.2 mg/dL

* jaundice is seen one levels rise to 2-40 mg/dL

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9
Q

Why do neonates always show with mild unconjugated hyper bilirubinemia?

A

termed neonatal jaundice

Due to the hepatic machinery required to excrete bilirubin is not fully mature until about 2 weeks of age

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10
Q

Gilbert syndrome

A

Common (7%) inherited condition where unconjugated bilirubin levels are high due to mildly decreases hepatic levels of glucuronosyltransferase enzymes

This is a direct cause of UGT1A1 mutations

there are no other associated morbidities

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11
Q

Crigler-Najjar syndrome type 1

A

Rare form of Gilbert disease where the mutations are way more prominent and the unconjugated hyperbilirubinemia is very severe (like off the charts)
- has almost no glucuronosyltransferase enzymes

almost always fatal in infancy

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12
Q

Dublin-Johnson syndrome

A

Autosomal recessive defect in transport proteins responsible for hepatocellular excretion

exhibits CONJUGATED/direct hyperbilirubinemia

Hepatomegaly and dark livers are seen, but usually asymptomatic outside of that.

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13
Q

Cholestasis

A

Condition caused by extrahepatic or intrahepatic obstruction of bile channels or defects in hepatocyte bile secretions

Can present with:

  • jaundice
  • pruritus
  • skin xanthomas
  • intestinal malabsorption
  • deficency in DAK vitamins

Diagnosis:

  • symptoms
  • also elevated serum alkaline phosphatase and GGT enzymes in both hepatocytes and cholangiocytes
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14
Q

What are the most common causes of bile duct obstruction?

A

Adults = gallstones, malignant obstructions and post surgical strictures (in this order)

Children = biliary atresia, CF, choledochal cysts (in this order)

most of these are reversible, but if not fixed will cause cirrhosis

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15
Q

What is ascending cholangitis?

A

Secondary bacterial infections that get into the biliary tree and that either causes duct obstruction or compounds already present duct obstruction

Symptoms:

  • fever
  • chills
  • ab pain
  • jaundice
  • *becomes suppurative cholangitis if Purulent bile fills (this is the most severe form of cholangitis)**
  • usually also presents with sepsis
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16
Q

What is the most common treatment for extrahepatic biliary obstruction?

A

Surgical treatment

note you CANT use this for intrahepatic cholestasis

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17
Q

What are the two most common autoimmune cholangiopathies?

A

1) primary biliary cholangitis

2) primary sclerosing cholangitis

18
Q

Primary biliary cholangitis (PBC)

A

Disease of middle aged women primarily

  • 6x more likely in 40-50 yr old females
  • most prevalent in Northern European countries and northern United States (Minnesota)

Is a progressive disorder tied well to sjogren syndrome (70%) and thyroid disorders (20%)
- also mild ties to sclerosis, RA, raynaud phenomenon and celiac disease

Unknown trigger but always presents with anti-mitochondrial antibodies (AMA) and “florid duct lesions” in histology of interlobular bile ducts

19
Q

What happens in PBC if it is not treated?

A

Follows one of 2 pathways

1) classic pathway = widespread intrahepatic duct loss leading to cirrhosis and cholestasis
2) alternative pathway = same as classical pathway except it ends with cirrhosis and portal HTN

20
Q

Symptoms of PBC

A

Most are asymptomatic

Most are determined based on a work up for unrelated issues

  • shows serum alkaline phosphatase
  • also always shows anti-mitochondrial antibodies (AMA)

If symptoms are present, its usually increased fatigue and pruritus

21
Q

Treatment for PBC

A

Early treatment = oral ursodeoxycholic acid
- doesnt cure and usually only delays progression

Late stage treatment = liver transplantation

22
Q

What are secondary features of PBC (even with treatment)?

A

Skin hyperpigmentation

Xanthelasmas

Steatorrhea

Vitamin D malabsorption

Osteomalacia

23
Q

Primary sclerosing cholangitis (PSC)

A

Inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts
- causes dilation of preserved segments

More common in males in the 30-50s

shows “beading” of the intrahepatic and extrahepatic biliary tree
(Looks like beads lodged in the hepatic tree)

most commonly associated with IBD (especially Ulcerative colitis (70%)) and pancreatitis (25%)

Diagnosis = radiographic imaging of the biliary tree ducts (look for beading)

24
Q

What are pathogenic features of PSC?

A

Believed to be T-cell mediated autoimmune process that get activated from the mucosa of patients with UC or pancreatitis

These T-cells migrate to the liver where they cross-react with bile duct antigens and initiate autoimmune assaults
- pANCA is the most heavily tied autoimmune antibody to PSC (80% of PSC patients have this)

25
Q

How does histology change with PSC?

A

Shows onion skin fibrosis and strictures that look kinda similar to UC histology
- nicknamed the “tombstone” scar

26
Q

PSC clinical features

A

Generally asymptomatic until the disease progresses
- ** as seen in PBC, most patients are incidentally found due to elevated serum alkaline phosphatase

Will inevitably progress to liver cirrhosis and cholestasis
- has high levels of cholangiocarinoma as well (7%)*

Other symtpoms:

  • progressive fatigue
  • pruritis
  • jaundice
  • chronic pancreatitis or chronic cholecystits
27
Q

Treatment of PSC

A

There isnt any 1st line treatment

  • course usually lasts 5-17 years
  • usually just give endoscopic dilation and stents to relive obstructions when they present

liver transplant once end-stage liver disease presents

28
Q

Hepatocellular carcinoma(HCC)

A

Anaplastic lesions that develop from hepatocytes

  • usually diagnosed incidentally or via imaging for other reasons
  • makes up 5.4% of all cancers

Occasionally rupture which can lead to life-threatening intra-abdominal bleeding

increased sex hormone exposure (anabolic steroids or oral contraceptives) markedly increases frequency of these tumors

Peak incidence of HCC is seen between ages 20-40yrs in endemic regions and 60yrs in western populations
- more common in men than women (3x in western countries and 8x in endemic regions)

Highest incidence is seen in Asia and sub-Saharan Africa regions

  • 85% of cases occur in areas with high rates of chronic HBV and HBC infections**
  • also exposure to alfatoxin increases risk**
29
Q

Why is HCC almost tripled the incidence in the United States?

A

Because of increasing prevalence of hepatitis C
- is considered more dangerous in western countries because over 90% of the time, when it is caught in western countries, cirrhosis and malignancy is already present

30
Q

What is the most common pathology associated with HCC?

A

Chronic liver disease
- DOESNT need cirrhosis to diagnose, however almost always is present at the same time

  • *most important underlying factors**
  • HBV/HCV/Alfatoxin exposure/chronic alcoholism
  • a1-AT deficency and Wilson disease
  • NAFLD and obesity
  • diabetes
31
Q

What species of bacteria is most known for producing alfatoxin?

A

Aspergillus species

32
Q

What are the most common driver mutations in HCC?

A

Gain-o-function mutations in B-catenin and loss-o-function in p53

33
Q

Clincial signs of HCC

A

Is often masked by cirrhosis or hepatitis

Symptoms:

  • ill-defined upper abdominal pain
  • malaise
  • fatigue
  • weight loss
  • abdominal fullness/mass feeling constantly
  • jaundice
  • fever
  • GI/esophageal varices

Lab results:

  • elevated “a-fetoprotein” levels
  • imagine studies show mass in liver

majority of patients die within 2 years of diagnosis if it is large or has Mets (if not surgical resection may be enough)

34
Q

Cholangiocarcinoma (CCA)

A

2nd most common primary malignant tumor of the liver

  • accounts for 3% of all GI cancers
  • *endemic to regions with high levels of river flukes as well (Southeast Asia)

Risk factors:

  • getting infected with river flukes
  • HBV/HCV
  • NAFLD
  • chronic inflammatory diseases of bile ducts (PSC especially)
35
Q

How does tumor morphology differ between extrahepatic CCA vs intrahepatic CCA?

A

Extrahepatic = small numerous lesions
- often shows liver cirrhosis

Intrahepatic = large singular lesions
- often doesnt show cirrhosis

36
Q

What does histology of CCA show?

A

Mucin-producing glandular tissue in liver biopsy

37
Q

Gallstones

A

Affect 10-20% of western country populations and 20-40% of Latin American countries
- only 3-4% of Asian countries though

Two main types:

1) cholesterol stones (crystalline cholesterol monohydrate stones)
- are made up of 50-100% cholesterol (rest is calcium carbonate
- radiolucent and yellow

2) pigment stones (bilirubin calcium salts)
- contains unconjugated bilirubin
- radioopaque and black/blue

occurs when cholesterol concentrations exceed the solublizing capacity of bile

38
Q

Risk factors for gallstones

A

Female and older than 50 yrs
- 80% of people with gallstones only have these 2

Pregnancy

Obesity

Diabetes

Use of oral contraceptives

Losing weight quick

IBD (especially CD)

Chronic hemolysis (spherocytosis and Sickle cell are the most common)

39
Q

Cholecystitis

A

one of the most common indications for abdominal surgery in the US

Acute or chronic inflammation of the gallbladder

is called “acute calculous cholecystitis” if gallstones are also present at the same time (this is the case in 90%)

40
Q

Carcinoma of the gallbladder

A

Most common malignancy of the extrahepatic biliary tract

More common in women and over the age of 70

Very rarely ever caught before it becomes malignant
- mean 5yr survival rates are5-12% because of this

  • most important risk factor = gallstones*
  • PSC is the next most importaint

Gastrointestinal (71 decks)

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