Module 2: GI: Colon Cancer, Appendicitis, Hepatitis and Cirrhosis Flashcards Preview

Pathology Post Midterm > Module 2: GI: Colon Cancer, Appendicitis, Hepatitis and Cirrhosis > Flashcards

Flashcards in Module 2: GI: Colon Cancer, Appendicitis, Hepatitis and Cirrhosis Deck (48):
1

To finish off cancer and polyps of the colon. I will discuss Colon Adenocarcinoma. Describe the gross and histological images in slide 20

Tumors in proximal colon: grow as polyploidy, exophytic masses (cauliflower appearance)
Tumors in distal colon: tend to be annular lesions that produce napkin ring constriction and luminal narrowing
--both grow into the bowel wall over time and become palpable firm masses
Barium Enema Xray: apple core lesion in the sigmoid colon
Histopathology: malignant glands invading the submucosa and muscularis propia (sequential process) --can invade the serosa next -- lymph nodes
--note carcinoma once broken through the submucosa

2

What are the predisposing factors for colon adenocarcinoma?

Mostly sporadic and in patients over 50
Pre-disposing factors: FAP (Genetic), HNPCC (genetic), high fat diet, low fiber, diet rich in refined carbs, low in vitamins A,C, and E, ulcerative colitis and Crohn's

3

What is the pathogenesis for colon adenocarcinoma?

Two molecular pathways:
1.APC/B-catenin pathway (chromosomal instability pathway) (85%-90%) of cases::
---normal colon, then loss of APC gene (born with one hit this is the additional hit) ---> decreased intercellular adhesion and increased proliferation
--colon at risk, KRAS mutation → unregulated intracellular signal transduction
---Adenoma, loss of tumor suppressor genes ---> increased tumorigenesis
--Carcinoma
2. Microinstability Pathway (10-15%) of cases:
--may arise from adenomas or other lesions
--defect in DNA mismatch repair genes (MLH1, MSH2, MSH6 and PMS)
--85% are sporadic and 15% familial (HNPCC/lynch syndrome)
Signet ring cells = E-cadherin mutation

4

What are the common sites for adenocarcinoma?

Recto sigmoid, ascending, descending

5

What are the signs and symptoms for adenocarcinoma?

Ascending Colon (Right sided): occult bleeding leading to iron deficiency anemia (Esp in males over 50 and postmenopausal women) ---> fatigue
Descending Colon (Left sided): bright red blood, mucus and napkin ring constriction on gross → more likely to cause intestinal obstruction → pencil shaped stools
--Usually solitary

6

What investigations can be done for adenocarcinoma?

Screen patients over 50 with colonoscopy
If suspect colon cancer:
Barium enema study before taking a biopsy
CEA tumor marker: good for monitoring recurrence not useful for screening

7

What is he course/complications for adenocarcinoma?

Metastasis to the regional lymph nodes and then to the liver (liver drains the GI) then the lungs
If metastasis than survival rate is 4%
TNM staging determines the prognosis

8

Finally the last thing to discuss in the GIT will be appendicitis. What is the etiology?

Fecal obstruction of the lumen of the appendix (most common)

9

What is the pathogenesis for acute appendicitis?

Obstruction --- continued secretion of mucinous fluid --- increased intraluminal pressure --- collapse of draining veins ---- ischemic injury ---- bacterial proliferation --- inflammation and edema

10

What are the symptoms for appendicitis?

Periumbilical Pain that then moves to the RLQ (McBurney's Point), nausea, vomiting and rebound tenderness
---periumbilical pain first due to visceral peritoneum
--RLQ pain, they can now localize the pain

11

What does the biopsy look like for appendicitis?

Presence of neutrophils all the way to the muscularis propria
--therefore a pathologist can tell its appendicitis because inflammation all the way down to the muscularis propria

12

What do you see on CBC in a patient with appendicitis?

Increased neutrophils (Due to the inflammation)
Bands cells (leukomoid reaction and left shift)

13

On physical examination what signs is the patient positive for?

Rovsing
Psoas
Obturator Sign

14

What are complications of appendicitis?

Perforation
Peritonitis
Peri-Appendiceal Abscess
Liver abscess
Bacteremia

15

Now moving onto liver pathology. The first major thing to discuss is the various hepatitis's. Give the features of Hep A.

Caused by a single stranded RNA virus
Fecal-oral route
No chronicity
No carrier state
Increased incidence in travelers
Common in children
Check IgM levels for recent infection

16

Give the features of Hep B

Hep B (serum hepatitis):
Cause by enveloped DNA virus with a long incubation period (4-26 weeks)
Transmission: transfusion of blood, sexual intercourse, IV drug abuse, homosexuals, needle stick injuries
High risk of malignant transformation and increased incidence in developing countries
Histology: Ballooning degeneration and ground glass appearance of hepatocytes
Carrier state

17

Give features of Hep C

Most important cause of transfusion associated hepatitis and chronic liver disease
Parenteral route; chronic and persistent
Inherently unstable virus so no vaccine yet
Histology: extensive macrovasicular and microvesicular steatosis; damage to the portal tracts and alot of apoptotic bodies

18

Give features of Hep D.

Parenteral Route
Co infection and superinfection with hepatotropic virus
Super infection is more dangerous
Co-infection with Hep B
Super infection so Hep D superimposed on present Hep B

19

Give features of Hep E.

Hep E:
fecal oral route
No chronicity (unless immunosuppressed post liver transplant patient)
High mortality in prego females
Severe cholestasis which persists for longer periods

20

The next hepatitis to touch on briefly is autoimmune hepatitis. What population is this seen in and what is the etiology

Middle aged women
--associated with HLA DR3/DR4
--triggers: infection, drugs and herbal products
--can overlap with primary sclerosing cholangitis or primary biliary cirrhosis

21

What is the histology of autoimmune hepatitis?

Clusters of lymphocytes and plasma cells in the interface of portal tracts and hepatic lobule

22

What are appropriate investigations for autoimmune hepatitis?

Type 1: ANA & Anti-smooth muscle Ab (ASMA)
Type 2: Anti-liver kidney microsome-1 (ALKM-1)

23

What are appropriate treatments for autoimmune hepatitis?

Immunosuppression
Liver transplant

24

What are complications of autoimmune hepatitis?

1. Fulminant hepatitis: denotes clinical hepatic insufficiency that progresses rapidly to hepatic encephalopathy within 2-3 weeks (massive, submassive necrosis) (viral hepatitis most common cause)
2. Liver cirrhosis

25

Now moving onto the big topic of cirrhosis, what are the three defining features of cirrhosis?

1. Bridging fibrous septa
2.Parenchymal nodules created by regeneration
3. Architectural disruption

26

What is a general definition of cirrhosis?

Fibrosis of the liver due to a number of reasons
-Hep C is the most common cause in the US

27

What are causes of cirrhosis, each card will go through them?

1. Chronic Alcoholism: steatosis (Fatty change)--- hepatitis (AST/ALT greater than 2) --- cirrhosis
-See Mallory Bodies (intermediate filaments as eosinophilic cytoplasmic inclusions)
--micronodular --- macronodular (greater than 3cm)

28

What is another cause of cirrhosis?

2. Hemochromatosis: increased iron, decreased TIBC
--gives you DM (Bronze diabetes)
--increased skin pigmentation
--cardiomyopathy
--serum iron elevated
TIBC low
Transferrin saturation is high

29

What is the third cause of liver cirrhosis?

3. Primary biliary cirrhosis (this will be another slide)
--anti-mitochondrial Ab

30

What is the 4th cause of liver cirrhosis?

4. Non-Alcoholic Steatohepatitis
--associated with metabolic syndrome
(obesity, dyslipidemia, Impaired glucose tolerance, hypertension)
-this leads to cirrhosis

31

What is the 5th cause of liver cirrhosis?

5. Hepatitis B and C
--again C is the most common

32

What is the 6th cause of liver cirrhosis?

6. Wilson's Disease (AR)
--Kayser-Fleisher Rings in the eyes = sunflower cataracts
--Elevated Cu Levels
--Targets basal ganglia in the brain (causing flapping tremors)
--kidneys= stones and renal failure due to acute tubular necrosis
--Blood= free radicals that leads to hemolytic anemia (Coombs negative)
--Liver = cirrhosis

33

What is the 7th cause of liver cirrhosis?

7. Ulcerative Colitis
--due to primary sclerosing cholangitis (pANCA positive)
--beaded appearance of the biliary tree

34

What is the 8th cause of liver cirrhosis?

8. Auto-immune hepatitis:
--young females
--anti- smooth muscle antibodies
--high levels of IgG in the blood
--plasma cells and lymphocytes on histology

35

What is the 9th cause of liver cirrhosis?

9. A1AT deficiency (AR)
--presents in childhood
--panlobular emphysema in adulthood (with PiZZ mutation causing reduced levels) (see liver inclusions with PAS-diastase stain)
--low levels of alpha anti-trypsin (protease inhibitor that is a glycoprotein encoded by the PiMM gene on Chr14)
--misfolded proteins thats why kids get liver cirrhosis

36

What is the 10th cause of liver cirrhosis?

10. Budd Chiari Snydrome:
--obstruction of hepatic vein

37

What is the pathogenesis for liver cirrhosis?

Kupffer Cells secrete TGFbeta
---activate ito/stellate cells in space of Disse to deposit type III collagen ---- type I collagen
Loss of fenestration in endothelial cells -- impaired secretion of protein
New vascular channels in fibrous septae --- shunting blood
Obstruction of biliary channels --- jaundice
--note Ito cells normally store vit A (retinoic acid)

38

What is the presentation for Liver Cirrhosis?

Estrogen Metabolism impairment
--palmar erythema, spider nevi/angioma and testicular atrophy, gynecomastia
Finger Clubbing
Jaundice
Leukonychia (Due to low proteins)
Depuytren's Contractures

39

What are the investigations that are done for Liver Cirrhosis?

1.Biopsy is the most accurate
--trichrome stain for collagen
--Red is regenerating nodules of hepatocytes surrounded by blue collagen + fiber
2.AST,ALT bilirubin all elevated
--Elevated bilirubin and transaminases -- hepatocyte damage
--Elevated ALP and GGT = biliary tree damage
--Alcohol elevates GGT
3. Nodules on Gross
-regeneration hepatocytes
--less than 3mm micronodular
--greater than 3mm macronodular

40

What are the complications for liver cirrhosis?

1. Liver Failure
--Hepatic Encephalopathy: leads to back up of ammonia causing papilledema, asterix and brain swelling
2. Portal Hypertension
3. HCC
4. Trouble Making Clotting Factors: 2,7,9,10 -- elevated bleeding time and PT
5. Peripheral Edema and worsening ascites -- Hypoalbuminemia
6. Hypoglycemia

41

The last topic to be discussed is Primary Biliary Cirrhosis. What is the pathogenesis for this?

--More common in middle-aged women
Chronic (non caseating granulomatous) inflammation --- autoimmune (CD4T cell mediated) destruction of the medium sized intrahepatic bile ducts (type IV HSR)
--note non suppurative granulomatous destruction of medium sized bile ducts and this is how you distinguish this from TB
--only does intrahepatic so that is how you distinguish it from primary sclerosing cholangitis
--also a type II HSR due to the anti-mitochondrial bodies

42

What is the presentation of primary biliary cirrhosis?

Asymptomatic
Pruritis (itching) due to accumulation of bile salts is seen before jaundice (conjugated hyperbilirubinemia) (also seen in CML and PV)
Steatorrhea
Malabsorption of fat soluble vitamins in dark urine
Xanthoma, Xanthelasma (body is trying to compensate by making more cholesterol)

43

What investigations are done for primary biliary cirrhosis?

1. Liver Biopsy Most Accurate: Florid duct lesion
2. High ALP and GGT
3. High Conjugated bilirubin
4. AST and ALT only elevated very late
5. Anti-Mitochondrial Antibodies (Best investigation in the blood)

44

What are the complications of primary biliary cirrhosis?

1. Portal HTN
2. HCC
3. Hypoalbuminemia (peripheral edema + ascites)
4. Coagulopathy
5. MI and stroke (hypercholesterolemia)
6. Malabsorption of fat and fat soluble vitamins
7. Osteomalacia due to vit D malabsorption
8. Tetany and arrhythmia's again due to the vit D malabsorption that is resulting in hypocalcemia

45

What is the most common primary tumor?

Diffuse Gastric
Colon
Breast

46

What is a Jelly Belly in regards to acute appendicitis?

Mucoceal (excess mucus in the lumen of the appendix) and if appendix ruptures then you get a Jelly Belly

47

What is the appearance on histology of Primary Biliary Cirrhosis?

Florid Duct Appearance
--contains CD4 T cells, fibroblasts and epitheloid histocytes

48

On the image for liver cirrhosis what do the nodules represent?

Regeneration of hepatocytes (Can be micro or macro) and can go from micro to macro

Decks in Pathology Post Midterm Class (50):