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Pathology > Histopathology Part 2- (p149-166- GI, Pancreatic + Liver) > Flashcards

Histopathology Part 2- (p149-166- GI, Pancreatic + Liver) Flashcards

1
Q

What is the epithelial cytology of the oesophagus?

A

Squamous epithelium for proximal 2/3
Columnar epithelium for distal 1/3
Joined by Z line/squamo-columnar junction

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2
Q

What is the commonest cause of oesophagitis?

A

GORD

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3
Q

What are the complications of GORD?

A

Ulceration, haemorrhage->haematemesis or melaena, Barret’s oesophagus, stricture, perforation

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4
Q

How is GORD treated?

A

Lifestyle- stop smoking, weight loss

PPI/H2 receptor antagonists

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5
Q

What is Barrett’s oesophagus?

A

Intestinal metaplasia of squamous mucosa -> columnar epithelium -> upwards migration of z line
Can lead to adenocarcinoma

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6
Q

Risk factors for squamous cell oesophageal carcinoma?

A 
ETOH
Smoking
Achalasia of cardia
Plummer-Vinson syndrome
Nutritional deficiencies
Nitrosamines
HPV
6x more common in Afro-carribeans
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7
Q

How does squamous cell oesophageal carcinoma present?

A 
Progressive dysphagia (solids -> fluids)
Odynophagia (pain)
Anorexia
Severe weight loss
Rapid growth and early spread to LN, liver and to proximal strictures
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8
Q

What are varices?

A

Engorged dilated veins usually due to portal HTN

Pt vomits units of blood

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9
Q

How do you treat varices?

A

Emergency endoscopy -> sclerotherapy/banding

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10
Q

How do gastric ulcers present clinically?

A

Epigastric pain +/- weight loss

Worse with food, relieved by antacids

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11
Q

RFs for gastric ulcer?

A

H. pylori, smoking, NSAIDs, stress, delayed gastric emptying, elderly

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12
Q

Histology of gastric ulcer?

A

Breach through muscularis mucosa into submucosa

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13
Q

What causes gastric lymphoma?

A

H. pylori- chronic antigen stimulation

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14
Q

How do you treat gastric lymphoma?

A

Remove H.pylori using triple therapy- PPI, clarithromycin + amoxicillin or metro

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15
Q

How does duodenal ulcer present clinically?

A

4x more common than GU
Epigastric pain worse at night
Relieved by food and milk
Younger adults

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16
Q

RFs for duodenal ulcers?

A 
H. pylori
Drugs
Aspirin
NSAIDs
Steroids
Smoking
Drugs
Acid secretion
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17
Q

What is the pathophysiology of coeliac disease?

A

T cell mediated autoimmune disease (DQ2 or DQ8), gluten intolerance results in villous atrophy and malabsorption

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18
Q

How does coeliac disease present?

A 
Young children and Irish women- EMQ
Steatorrhoea
Abdo pain
Bloating
N+V
Weight loss
Fatigue
IDA
Failure to thrive
Rash
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19
Q

Serological tests for coeliac disease?

A

Anti-endomysial ab, anti-tissue transglutaminase, anti-gliadin

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20
Q

Gold standard Ix for coeliac disease?

A

Upper GI endoscopy and duodenal biopsy

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21
Q

Treatment of coeliac?

A

Gluten free diet

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22
Q

What is Hirschsprung’s disease and how does it present clinically?

A

Absence of ganglion cells in the myenteric plexus (Genetics- RET proto-oncogene Cr10+)
Presents with symptoms and signs of obstruction in young babies, mainly males

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23
Q

How is Hirschsprung’s treated?

A

Resection of affected segment

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24
Q

Causes of bowel obstruction?

A

Constipation
Diverticular disease
Adhesions
Herniation
External mass e.g. fetus, aneurysm, foreign body
Volvulus- complete twisting of bowel loop at mesenteric base around vascular pedicle, small bowel
Intussusception

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25
Epidemiology of Crohn's?
Western population Peak onset 20s, F>M White 2-5x>non-white Smoking worsens symptoms
26
Epidemiology of UC?
Slightly more common White>non-whites Peak age 20-25
27
Aetiology of Crohns?
Unknown MZ twin concordance 50% Hygiene hypothesis
28
Aetiology of UC?
Unknown | MZ twin concordance 15%
29
Pathophysiology of crohn's?
Whole GI tract (mouth to anus)- most common terminal ileum and caecum Patchy distribution -> 'skip lesions' Healthy mucosa lies above diseased mucosa -> cobblestone appearance Aphthous ulcers (rosethorn) Non caseating granulomas seen Transmural inflammation Fistulas and fissures common
30
Pathophysiology of UC?
Extends proximally from rectum Continuous involvement of mucosa Small bowel not affected normally Extensive superficial broad ulcers Inflammation confined to mucosa No granulomas/fissures/fistulae/strictures Islands of regenerating mucosa bulge into lumen -> pseudopolyps
31
Clinical features of crohn's?
Intermittent diarrhoea Pain Fever
32
Clinical features of UC?
Associated more with bloody diarrhoea, mucus | Crampy abdo pain relieved by defecation
33
Extra GI manifestations of IBD?
``` A PIE SAC Aphthous ulcers Pyoderma gangrenosum Iritis Erythema nodosum Sclerosing cholangitis Arthritis Clubbing of fingertips ```
34
Complications of Crohn's?
Strictures (requiring bowel resection) Fistulae Abscess formation Perforation
35
Complications of UC?
Severe haemorrhage Toxic megacolon -> perforation 30% require colectomy within 3y Adenocarcinoma (20-30x risk)
36
Ix for Crohn's?
Systemic markers of inflammation e.g. ESR, CRP, Barium contrast, endoscopy
37
Ix for UC?
Rectal biopsy Flexi sig/colonoscopy AXR Stool culture
38
Management of Crohn's?
Mild- Prednisolone Severe- IV hydrocortisone, metronidazole Additional- azathioprine, methotrexate, infliximab
39
Management of UC?
Mild- pred + mesalazine Mod- Pred + Mes + steroid enema bd Severe- Admit, nbm, IV fluids and IV hydrocortisone, rectal steroids Remission- Mes + azathioprine (2nd line)
40
What is the pathophysiology of c difficile infection?
Use of abx e.g. cipro or ceph's kill off commensals allowing c.diff to flourish. It's exotoxins cause pseudomembranous colitis
41
How do you investigate c diff infection?
Stool culture
42
How do you treat c difficile infection?
Metronidazole (covers anaerobic) or vancomycin (2' line)
43
What is probably responsible for the high incidence of diverticular disease in the west?
A low fibre diet
44
What is the pathophysiology of diverticular disease?
High intraluminal pressure results in outpouchings at weak points in the bowel wall (can be seen on barium enema CT or endoscopy)- 90% occur in left colon- often asymptomatic but sometimes PR bleed
45
Complications of diverticular disease?
Diverticulitis- fever and peritonism, gross perforation, fistula, obstruction (due to fibrosis)
46
What is carcinoid syndrome?
Diverse group of tumours of enterochromaffin cell origin which produce 5-HT (serotonin) Commonly found in bowel and usually slow growing Presents with bronchoconstriction, flushing and diarrhoea Can lead to carcinoid crisis
47
How do you investigate carcinoid syndrome?
24h urine 5-HIAA (main metabolite of serotonin)
48
How do you treat carcinoid syndrome?
Octreotide- somatostatin analogue
49
What is an adenoma?
Benign dysplastic lesions that are the precursor to most adenocarcinomas Found in 50% >50y in western world
50
Most important risk factor for malignancy in adenomas?
Large size, in addition to dysplasia and increased villous component
51
What types of non-neoplastic polyps are there?
Hamartomatous polyp Hyperplastic polyp Inflammatory- pseudopolyp
52
What is the second most common cause of cancer death in UK?
Colorectal
53
What percentage of colorectal cancers are adenocarcinoma?
98%
54
Aetiology of colorectal cancer?
Diet (low fibre, high fat), lack of exercise, obesity, familial syndromes, chronic IBD
55
Investigations in colorectal cancer?
``` Protoscopy Sigmoidoscopy Colonoscopy Barium enema Bloods e.g. FBC CT/MRI Carcinoembryonic antigen (CEA)- monitor disease ```
56
With which system and how is colorectal cancer staged?
``` Duke's staging- helps decide treatment A- confined to mucosa B1- extending into muscularis propria B2- transmural invasion, no LN involved C1- Extending into muscularis propria, with LN metastases C2- transmural invasion with LN mets D- distant mets ```
57
How is colorectal cancer managed?
Surgery Radiotherapy- post-op to decrease local recurrence Chemo in palliation- 5-FU
58
What mutations are responsible for familial adenomatous polyposis (FAP)?
70% AD mutation in APC gene (C5q1) | 30% AR mutation in DNA mismatch repair genes
59
How does FAP present?
Around 10-15y, >100 adenomatous polyps- ALL will progress to adenocarcinoma if not treated by 30 so prophylactic colectomy
60
What mutations are responsible for hereditary non-polyposis colorectal cancer (HNPCC)?
AD mutations in DNA mismatch
61
What is the role of the pancreas?
Produces 2L a day of enzymic HCO3- rich fluid, stimulated by secretin and CCK
62
Where is secretin produced and what does it do?
Produced by s-cells of duodenum, controls gastric acid secretion and buffering with HCO3-
63
Where is cholecystokinin (CCK) produced and what does it do?
Made by I-cells in duodenum. | Responsible for stimulating digestion of fat and protein by causing release of digestive enzymes
64
What are the exocrine functions of the pancreas?
Secretes digestive enzymes into ducts- proteases, lipases and amylase
65
What are the endocrine functions of the pancreas?
Secretes products e.g. hormones into blood stream Alpha cells- glucagon Beta cells- insulin Delta- Somatostatin regulates above cells D1- Vasoactive peptide, stimulates secretion of H2O into pancreatic system
66
How do you diagnose DM?
Fasting plasma glucose>7 | or random plasma glucose >11.1
67
What is the pathophysiology of T1DM?
Autoimmune destruction of beta cells by CD4+ and CD8+ T lymphocytes, may present with DKA
68
Pathophysiology of T2DM?
Linked to obesity and insulin resistance
69
Complications of diabetes?
Macrovascular- cardiac, renal, cerebral Microvascular- retinopathy, PVS Other- polydipsia, polyuria and recurrent infections
70
What score is used to assess acute pancreatitis?
GLASGOW- 3 or more leads to ITU referral
71
Causes of acute pancreatitis?
``` I GET SMASHED Idiopathic Gallstones Ethanol Trauma Steroids Mumps Autoimmune Scorpion venom Hyperlipidaemia ERCP Drugs e.g. thiazides ```
72
Presentation of acute pancreatitis?
Severe epigastric pain radiating to back, relieved by sitting forward Vomiting prominent Amylase only transiently increased, serum lipase is more sensitive Can lead to pseudocyst formation
73
Histology of acute pancreatitis?
Coagulative necrosis
74
Causes of chronic pancreatitis?
``` Alcoholism Cystic fibrosis Hereditary Pancreatic duct obstruction e.g. stones/tumour Autoimmune- IgG4 sclerosin ```
75
Presentation of chronic pancreatitis?
Epigastric pain radiating to back, malabsorption due to lack of enzymes to digest food
76
Histology of chronic pancreatitis?
V similar to Ca pancreas- fibrosis and loss of exocrine tissue, duct dilatation with thick secretions, calcification
77
Presentation of acinar cell carcinoma?
Non-specific sx, abdo pain, wt loss, nausea and diarrhoea
78
Histopathology of acinar cell carcinoma?
Neoplastic epithelial cells with eosinophilic granular cytoplasm. Positive immunoreactivity for lipase, trypsin and chymotrypsin
79
Prognosis of acinar cell carcinoma?
Median survival 18m from diagnosis. 5y survival <10%
80
Most common pancreatic malignancy?
Ductal adenocarcinoma of pancreas (85% of all pancreatic malignancies) M>F
81
RF for pancreatic carcinoma?
Smoking Diet Genetic e.g. FAP, HNPCC
82
Clinical features of pancreatic carcinoma?
``` Weight loss and anorexia Upper abdo and back pain Jaundice (PAINLESS), pruritis, steatorrhoea DM Trousseau's syndrome (25%)- recurrent superficial thrombophlebitis Ascites Abdo mass Virchow's node Courvoisier's sign ```
83
Ix in pancreatic carcinoma?
Bloods- low Hb, raised Bili + Ca2+ CT/MRI/ERCP Ca19-9 >70IU/mL
84
Management of pancreatic carcinoma?
Chemotherapy is palliative (5-FU) Surgery- Whipple's procedure Prognosis v poor- <5% 5y survival
85
What are the different types of multiple endocrine neoplasia (MEN)?
MEN1- PPP- Parathyroid hyplasia, pancreatic endocrine tumour (often phaeo), pituitary adenoma MEN2A- Parathyroid, thyroid, phaeo MEN2B- Medullary thyroid, phaeo, neuroma, marfanoid phenotype
86
What are the 5 main functions of the liver?
Metabolism- glycolysis, glycogen storage, glucose, amino acid and fatty acid synthesis, hormone, lipoprotein and drug metabolism Protein synthesis- makes all circulating proteins except gamma globulins Storage- glycogen, vit A, D, B12, K, folate, iron + copper Bile synthesis- 600-1000ml daily Immune function- antigens from gut reach liver via portal circulation. Phagocytosed by Kupffer cells
87
What benign liver tumours are there?
Hepatic adenoma | Haemangioma
88
What malignant liver tumours are there?
``` Hepatocellular carcinoma Angiosarcoma Hepatoblastoma Cholangiocarcinoma Metastases from other primary tumours ```
89
What drug is hepatic adenoma associated with?
OCP
90
Causes of hepatocellular carcinoma?
Hep B+C, alcoholic cirrhosis, haemochromatosis, NAFLD, aflatoxin, androgenic steroids
91
Investigations for hepatocellular carcinoma?
Alpha-fetoprotein | USS
92
Causes of cholangiocarcinoma?
``` PSC Parasitic liver disease Chronic liver disease Congenital liver abnormalities Lynch syndrome type II ```
93
Most common malignant liver lesion?
Mets from other primary tumours- GI tract, breast or bronchus
94
Define cirrhosis?
Diffuse abnormality of liver architecture that interferes with blood flow and liver function- hepatocyte necrosis, fibrosis, nodules, portal HTN
95
7 major causes of cirrhosis?
``` Alcoholic liver disease Non-alcoholic fatty liver disease Chronic viral hepatitis Autoimmune hepatitis Biliary- PBC + PSC Genetic- haemochromatosis, Wilson's, alpha-1 antitrypsin deficiency etc Drugs- e.g. methotrexate ```
96
How is cirrhosis classified?
According to nodule size: Micronodular <3mm- uniform liver involvement- caused by alcoholic hepatitis or biliary tract disease Macronodular >3mm- variable nodule size- caused by viral hep, Wilson's or alpha-1 antitrypsin def
97
What is used to indicate prognosis in liver cirrhosis?
Modified Child's Pugh Score
98
What is the pathophysiology of portal HTN?
Increased portal pressure secondary to increased vascular resistance in liver, hyperdynamic circulation, sodium retention and plasma volume expansion Leads to venous system dilating and collateral vessels forming
99
Causes of portal HTN?
Prehepatic- portal vein thrombosis (e.g. Factor V Leiden) Hepatic- pre-sinusoidal- schistosomiasis, PBC, sarcoid, sinusoidal- cirrhosis, post-sinusoidal- veno-occlusive Post-hepatic- Budd-Chiari syndrome (occlusion of hepatic vein)
100
What are the macroscopic characteristics of hepatic steatosis (fatty liver)?
Large, pale, yellow and greasy liver
101
What are the microscopic characteristics of hepatic steatosis (fatty liver)?
Steatosis- accumulation of fat droplets in hepatocytes | Chronic exposure -> fibrosis
102
How can hepatic steatosis be reversed?
Fully reversible if alcohol avoided
103
What are the macroscopic characteristics of alcoholic hepatitis?
Large fibrotic liver
104
What are the microscopic characteristics of alcoholic hepatitis?
Hepatocyte ballooning and necrosis due to accumulation of fat, water and proteins Mallory bodies Fibrosis
105
What are the macroscopic characteristics of alcoholic cirrhosis?
Yellow-tan, fatty, enlarged | Transforms into shrunken non-fatty brown organ
106
What are the microscopic characteristics of alcoholic cirrhosis?
Micronodular cirrhosis- small nodules + bands of fibrous tissue
107
What is most common cause of chronic liver disease in west?
Non-alcoholic fatty liver disease
108
Who does Non-alcoholic fatty liver disease commonly occur in?
Mainly in obese individuals with hyperlipidaemia/metabolic syndrome Diabetes also a RF
109
When does autoimmune hepatitis commonly occur?
Common with other autoimmune diseases e.g. coeliac, SLE, RA, thyroiditis, sjogrens, UC
110
What are the 2 different types of autoimmune hepatitis?
Type 1- ANA (antinuclear Ig), anti-SMA, anti-actin Ig, anti-soluble liver antigen Ig Type 2- Anti-LKM Ig
111
How do you treat autoimmune hepatitis?
Immune suppression until transplant, but disease returns in upto 40%
112
What is the pathology of Primary Biliary Cirrhosis (PBC)?
Autoimmune inflammatory destruction of medium sized intrahepatic bile ducts -> cholestasis -> SLOW development of cirrhosis
113
What is the F:M ratio of PBC?
10:1 | PSC is M>F
114
What would blood tests show in PBC?
Increased serum ALP, cholesterol, IgM, AMA in 90% and hyperbilirubinaemia
115
What would a US scan show in PBC?
No bile duct dilatation
116
What would histology of PBC show?
Bile duct loss with granulomas
117
How does PBC present?
Fatigue, pruritus, abdo discomfort, skin pigmentation, xanthelasma, steatorrhoea, vit D malabsorption, inflammatory arthropathy
118
How do you treat PBC?
Ursodeoxycholic acid in early phase
119
What is the pathology of primary sclerosing cholangitis (PSC)?
Inflammation and obliterative fibrosis of extrahepatic and intrahepatic bile ducts -> multi-focal stricture formation with dilation of preserved segments
120
What condition is PSC associated with and which condition does it increase your risk of?
IBD (especially UC) | Risk- Cholangiocarcinoma
121
What would blood tests show for PSC?
Increased serum ALP, several auto-Ig especially p-ANCA
122
What would a US scan show for PSC?
Bile duct dilatation
123
What would an ERCP show for PSC?
Beading of bile ducts due to multifocal strictures
124
What are the 3 genetic causes of cirrhosis?
Haemochromatosis Wilson's disease Alpha1 antitrypsin deficiency
125
Inheritance pattern of haemochromatosis?
Autosomal recessive
126
What is the pathology of haemochromatosis?
Mutated HFE gene at 6p21.3 -> increased Fe gut absorption which deposits in liver, heart, pancreas, adrenals, pituitary, joints, skin -> fibrosis
127
What is the histology of haemochromatosis (and what stain would be used)?
Fe deposits in liver- stains with Prussian blue stain
128
Signs and symptoms of haemochromatosis?
``` Skin bronzing (melanin deposition) Diabetes Hepatomegaly with micronodular cirrhosis Cardiomyopathy Hypogonadism Pseudogout ```
129
What investigation findings would you see in haemochromatosis?
Increased iron and ferritin Transferrin saturation >45% Decreased TIBC
130
How do you treat haemochromatosis?
Venesection | Desferrioxamine
131
What age does Wilson's disease present?
11-14yo
132
Inheritance pattern of Wilson's disease?
Autosomal recessive
133
Pathology of Wilson's disease?
Mutated gene ATP7B- encodes copper transporting ATPase expressed on canalicular membrane -> decreased biliary Cu excretion and deposition in liver, CNS, iris
134
What does copper stain with?
Rhodanine
135
Signs and symptoms of Wilson's?
Liver disease- acute hepatitis, fulminant liver failure or cirrhosis Neuro disease- parkinsonism, psychosis, dementia Kayser Fleischer rings- copper deposits in Desemet's membrane in cornea
136
Investigation findings in Wilson's disease?
Decreased caeruloplasmin and serum copper | Increased urinary copper
137
Treatment for Wilson's disease?
Lifelong penicillamine
138
What is the inheritance pattern for Alpha1 antitrypsin deficiency?
Autosomal dominant
139
What is the pathology of A1AT deficiency?
A1AT accumulates in hepatocytes -> intracytoplasmic inclusions -> hepatitis Lack of A1AT in lungs -> emphysema
140
Histology of A1AT deficiency?
Intracytoplasmic inclusions of A1AT which stain with Periodic acid Schiff
141
Signs and symptoms of A1AT deficiency?
Neonatal jaundice in kids | Emphysema and chronic liver disease in adults
142
Investigation findings in A1AT deficiency?
Decreased A1AT | Absent alpha-globulin band on electrophoresis

Pathology (13 decks)

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