3 - Basic Principles of Liver Pathology Flashcards Preview

GI / Hepatology > 3 - Basic Principles of Liver Pathology > Flashcards

Flashcards in 3 - Basic Principles of Liver Pathology Deck (64)
1

The most common cause of abnormal LFTs in the US today!

Fatty liver

2

Liver Biopsy is used for

Grading & Staging of chronic hepatitis
Workup of possible fatty liver disease (alcoholic or non-alcoholic)
Evaluation of cholestasis & jaundice
Establish a tissue dx of tumor
Determine whether cirrhosis is present

3

Hepatocellular Diseases

Acute Hepatitis
Chronic Hepatitis
Fatty Liver Diseases
Metabolic Diseases (Genetic mutations: AAT def., Fe, Cu, inherited storage disorders)

4

Biliary Tract Diseases

Large bile duct obstruction (LBDO)
Intrahepatic bile ducts
Bile canaliculi/hepatocytes ("pure" or intrahepatic cholestasis)

5

Vascular Diseases

Central veins & sinusoids
Portal veins/hepatic arteries

6

Hepatitis - Most common etiologies

Infection by the Hepatitis Viruses
Drug Hepatitis

7

Hepatitis Viruses

HAV (28nm) - RNA (oral-fecal)
HBV (42nm) - dsDNA (genome incorporated into human genome, lead to cancer)
HCV (60nm) - RNA (also causes cancer in the liver)
HDV (30nm) - RNA (delta agent, parasite. Can't exist without HBV at the same time. You're a carrier for HBV, and then you shoot up with something contaminated with HDV)
HEV (32nm) - RNA (fecal-oral, meat)
Other viruses (CMV, HSV, etc)

8

Drug Hepatitis

Predictable (CCl4, acetaminophen)
Unpredictable (INH, aldomet)

9

Viral Hepatitis - Pathogenesis

Virus enters cell
Is encoded
Reproduces
Viral antigens are expressed on the hepatocyte membrane
CD8 cells kill that bitch

10

Drug Hepatitis - Pathogenesis

Predictable
Metabolite directly damages hepatocyte (Tylenol)
No immune system necessary

OR

Unpredictable
Metabolism in the liver of the drug, producing antigen "hapten" that binds the hepatocyte, causing T-Cells or Eosinophils to KILLLLLLLL

11

Acute Hepatitis

Does not mean neutrophils
Diffuse inflammation (lymphocytes)
Lymphocytes come through portal tract, infiltrate and spread towards central vein
Lobular disarray
Hepatocyte ballooning/apoptosis
"Spotty Necrosis"

12

Spotty Necrosis

Hepatitis, but can't tell if it's idiosyncratic or if it's viral

13

Massive hepatic necrosis

Seen in Fulminant Hepatitis
Viral causes are HAV & HBV
HEV can do it too in the nondeveloped world
Destroys all the hepatocytes in the damn liver.
Periportal progenitor/steam cell activation leads to formation of bile ductular structures. They tryna make up the difference gurl.
Wrinkled capsule!!!!!!
Occurs within 8 weeks of onset of infection/drug
Sometimes it creeps along for months

14

Fulminant Hepatitis

Occurs in 1 - 3 % of cases (between all acute viral and acute drug hepatites)

15

Submassive Necrosis

A thing he didn't explain

16

Chronic Hepatitis

Inflammation of the liver continuing without improvement for 6 months or longer

Disease process involving portal tracts/pp regions, lobules

17

Causes of Chronic Hepatitis

HBV
HCV
HDV (with co-presence of HBV)
Autoimmune hepatitis
Drugs (Hx of chronic intake)
2 metabolic diseases (α-1-antitrypsin deficiency, Wilson's)

18

Presenting Time of Wilson's

Not 60 years old. Younger? I missed it.

19

Grade 1

Sometimes modest inflammation only in the portal tracts, intermittently seeding out lymphocytes.

20

Grade 2

Ground glass Hepatitis B surface antigen inclusions. More inflammation getting out, "interface hepatitis."

21

Scarring

Scarring occurs, usually through stellate cells, making irregular portal tracts and thickened plates

22

Interface Hepatitis

Interface in all the portal tracts leads to increased fibrosis, losing all the hepatocytes.

23

Chronic Hepatitis - Grade 1

Minimal

24

Chronic Hepatitis - Grade 2

Mild

Includes interface hepatitis at the edge, some lobular as well

25

Chronic Hepatitis - Grade 3

Moderate

More circumferential

26

Chronic Hepatitis - Grade 4

Marked

Extensive interface and extensive lobular involvement

27

Chronic Hepatitis - Stage 1

Dots

28

Chronic Hepatitis - Stage 2

Dots with legs

29

Chronic Hepatitis - Stage 3

Stars

30

Chronic Hepatitis - Stage 4

Needlepoint

31

How can you tell on liver biopsy what caused the chronic hepatitis?

We may never know. I was taking notes on other shit

32

Hepatitis C Hallmarks

Once you have the virus chronically, the lymphoid system knows there is an antigen out there.
Takes over and sets up housekeeping in the portal tracts
Lymphoid aggregates form
Primary lymphoid follicle in the portal tract, essentially.
CLASSIC Hepatitis C

33

Autoimmune chronic hepatitis

Regenerative liver-cell rosettes
Interface hepatitis
Plasma cells

34

α-1-antitrypsin deficiency

Mutation in the gene for the gene product
New product doesn't exit well
Gets stuck in hepatocytes

Visible on DPAS as purple globules!!!

35

Wilson's Disease

Copper steigns for copper oh-ver-lode

36

Liver-Cell Dysplasia (LCD)

Pre-neoplastic lesion associated with HCC
Atypical nuclei
Seen in individuals with years of chronic hepatitis

Nuclear atypia:
Hyperchromatic
Convoluted contour
Prominent nucleoli
Multiple nuclei and nucleoli
Large hepatocytes

3/4 have cirrhosis first before progressing to cancer

37

Potential sequelae of acute viral hepatitis

Immune system clears virus
Resolution

38

Other potential sequelae of acute viral hepatitis (1 - 3%)

Immune system clears virus
Fulminant hepatitis

39

Other other potential sequelae of acute viral hepatitis (5% with HBV, 80% with HCV)

Poor CD4 response
Chronic hepatitis
Cirrhosis (with liver cell dysplasia)
HCC

40

Fatty Liver (Steatosis)

Will float in water
Large droplet vs. small droplet

41

Macrovesicular (large droplet) steatosis

Most common type of fatty liver
Due to alcohol, obesity, diabetes, corticosteroids
Droplets contain triglycerides
Increased Triglyceride synthesis or decreased Triglyceride excretion
Usually begins centrilobular, then moves to other regions

42

Microvesicular (small droplet) steatosis

Uncommon
Severe mitochondrial injury

Impaired β-FA oxidation:
Acute fatty liver of pregnancy
Reye's syndrome
Tetracycline toxicity
Nucleoside analogue toxicity
Valproic acid toxicity

43

Fatty Liver (large vacuole) and possible sequelae

Fatty liver
AFLD - Alcoholic fatty liver disease
NAFLD - Non-alcoholic fatty liver disease

Steatohepatitis (with peroxidation, swelling, fibrosis, etc)
ASH - Alcoholic steatohepatitis
NASH - Non-alcoholic steatohepatitis

Cirrhosis

44

Steatohepatitis

Fibrosis (activated Ito cells)
Steatosis (large droplet) inflammation
Intrahepatocellular Mallory bodies (or Mallory-Denk bodies)
Hepatocyte swelling (ballooning); cell injury

Fibrosis is "chicken-wire" centrilobular & pericellular/perisinusoidal

45

Mallory Denk Bodies

Circular inclusions that are like almost the size of a nucleus and they are just red, like a cherry red spot almost

46

Contents of Mallory Denk Body

Abnormal keratins (8 & 18) specific to hepatocytes. It is hyperphosphorylated or misfolded or crosslinked.

GET IT OUT!!

it's ubiquitinated, but doesn't make it out. It is evidence of steatohepatitis

P62 upregulation leads to aggregation

Overwhelms the proteosome/autophagy

Leads to micronodular cirrhosis (ASH or NASH)

47

Hit 1 - Causes fat

Alcoholics - Acetaldehyde
Non-Alcoholics - Obesity, diabetes, metabolic syndrome, certain drugs

48

Hit 1 - Causes steatohepatitis

Cytokines
Endotoxin

49

Large bile duct obstruction (LBDO)

Portal Edema
Neutrophils
Proliferation of bile ductular structures

50

Causes of LBDO

Gallstone obstruction
Cholelithiasis (gall stones)
Cholecystitis

Ampullary Carcinoma (pancreas)
Stricture (from scar)
Lymphoma or cancer in portall hepatitits lymph nodes
Cholangiocarcinoma (bile duct cancer)
Gallbladder cancer
Common bile duct cancer

51

Primary Sclerosing Cholangitis (PSC)

Younger patients
Hx of IBD (UC>Crohns)
Serum pANCA + 80%
Risk of Cholangio carcinoma
Periductal concentric "onion skin" fibrosis - diagnostic

Diagnose via ERCP

52

Primary Biliary Cirrhosis (PBC)

Targeting by antimitochondrial antibody that's an antigen on the intermitochondrial cristae

90% in females
10% in men

Serum positive antimitochondrial antibody
Partial destruction of interlobular bile ducts (one side but not the other!!!)
Does not affect large ducts

53

PBC

Middle aged women
+AntiMitochondrial Ab (M2 subtype)
Alk Phos up
It's like post-strep rheumatic fever! If you've had a Gram (-) UTI in the past, there are similar antigens on the inner cristae of the mitochondrial membrane (PDC-E2 - Pyruvate dehydrogenase complex - E2)
IgM up
Associated with other autoimmune diseases (RA, sicca, celiac, scleroderma

54

4 Stages of PBC

Stage 1 - Florid bile duct lesion
Stage 2 - Bile ductular proliferation
Stage 3 - Scarring
Stage 4 - Cirrhosis

55

Signs of Chronic Cholestasis

Jaundice + Scleral Icterus
Xanthelasma (eyelids)
Pruritus
Skin excoriations (from scratching)

56

Cholestasis - Retention of Pruritogen

Pruritis

57

Cholestasis - Increased serum bilirubin and serum lipids

Jaundice
Xanthomas

58

Cholestasis - Decreased bile acids entering intestine

Malabsorption of fat and fat-soluble vitamins
Steatorrhea
bone disease
coagulopathy
night blindness

59

Cholestasis - Hepatic accumulation of copper, bile acids, and other compounds

Exacerbation of liver damage

60

Vascular disease & the liver

Veins - Central/hepatic
Sinusoids
Arteries

Left HF (shock, hypotensive, septic) - Centrilobular Necrosis
Right HF - Centrilobular Congestion (nutmeg liver)
Both HF - Both!!

61

Budd-Chiari Syndrome

Hepatic Venous Outflow Obstruction

Thrombosis of hepatic vein/IVC
Tumor invasion of hepatic vein/IVC

OCPs
Coagulopathy (protein S, Protein C, Factor V leiden def, anti-cardiolipin Abs)
Tumor invasion (renal cell carcinoma + HCC)
Small vein disease (VOD "bush tea")

62

Cirrhosis - Many causes, pathologic features vary, depending on the cause, complications often similar

1 - Liver Failure
2 - Portal HTN
3 - Hepatocellular carcinoma

63

2 gross types of cirrhosis

Micronodular (nodules 3mm)

Both have diffuse fibrosis + architecturally abnormal regenerative nodules

64

Causes of cirrhosis

Chronic hepatitis - Chronic HBV, HCV, Autoimmune
Fatty liver disease - AFLD, NAFLD
Chronic biliary tract disease
Metabolic diseases (Hemochromatosis, Wilson's disease, α-1-antitrypsin deficiency (AAT deficiency))