Histopath - Liver & GI Flashcards

(114 cards)

1
Q

Granuloma - definition & diseases seen in

A

Organised collection of activated (epithelioid) macrophages

Seen in:

  • TB
  • Leprosy
  • Cat-scratch disease
  • Idiopathic reaction in sarcoid
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2
Q

General features of squamous cell carcinoma

A

Keratin production

Intercellular bridges

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3
Q

General features of Adenocacrcinoma

A

Mucin production

Glands

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4
Q

Histochemical stains

A

Fontana - melanin

Congo Red - ‘apple green birefringence’ (amyloid)

Prussian Blue - Iron (haemochromatosis)

Haematoxylin & Eosin - H stains basic parts purple/blue, E stains acidic parts red/pink

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5
Q

Rhodamine vs Rhodanine stains

A

RhodaMine = TB stain

RhodaNine = Wilson’s disease
- golden brown colour on blue counterstain

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6
Q

Histological features of EtOH liver disease

A

Fatty liver

  • large droplet fatty change
  • ‘large, pale, yellow, greasy’

Alcoholic hepatitis

  • mainly zone 3
  • fatty change
  • ballooning +/- Mallory Denk bodies
  • neutrophil polymorphs
  • pericellular fibrosis
  • megamitochondria
  • ‘large + fibrotic’

Liver failure

  • micro nodules of regenerating hepatocytes
  • surrounding fibrous cuff
  • +/- fatty change if currently drinking
  • ‘shrunken + brown’
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7
Q

Acute & Chronic hepatitis histological features

A

Acute hepatitis

  • spotty necrosis
  • usually concentrated around portal triad

Chronic hepatitis

  • viral = zone 1
  • portal inflammation
  • interface hepatitis ‘piecemeal necrosis’ (even though death is by apoptosis)
  • lobular inflammation (resembles acute spotty necrosis)
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8
Q

Overdose rule?

A
If PT (in seconds) > number of hours since OD
--> transfer to specialist liver unit for transplant
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9
Q

Pattern of nodule size in liver disease

A

MICROnodulae = alcoholic hepatitis, insulin resistance

MACROnodular = viral hepatitis, Wilson’s, Alpha-1-antitrypsin deficiency

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10
Q

Primary biliary cholangitis diagnostic features

A

Histology:

  • Bile duct loss
  • Chronic inflammation
    • granulomas

Other: Anti-mitochondrial antibodies e.g. anti M2 = gold standard

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11
Q

Primary sclerosing cholangitis diagnostic features

A

Histology:

  • concentric fibrosis
  • ‘onion skinning’

Bile duct imaging e.g. ERCP, MRCP

pANCA Ab detection

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12
Q

Autoimmune hepatitis diagnostic features

A

Histology:

  • extensive inflammatory infiltrate
  • abundant plasma cells
  • pale perinuclear area

Anti-smooth muscle actin Abs
Anti liver-kidney microsomal Ig

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13
Q

Hepatic granulomas - causes?

A

Specific: PBC, drugs
General: TB (caseating), sarcoid (non-caseating)

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14
Q

Normal range of bilirubin

A

5-17

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15
Q

Pre-hepatic causes of raised bilirubin

A

UNconjugated

Haemolytic anaemia

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16
Q

Hepatic causes of raised bilirubin

A

Hepatitis - viral, EtOH

Cirrhosis

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17
Q

Post hepatic causes of high bilirubin

A

Obstruction - gallstones, ca. head of pancreas

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18
Q

Ix needed for pre-hepatic (unconjugated) hyperbilirubinaemia

A

FBC
Blood film

Coomb’s test?

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19
Q

Genetics of Gilbert’s

A

Autosomal recessive

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20
Q

Pathogenesis + presentation of Gilbert’s

A

UDP glucoronyl transferase activity reduced to 30%

Causes slight jaundice
Worse when fasting/stressed
No bilirubin in urine (unconjugated bilirubin highly bound to albumin)

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21
Q

Best measure of liver (synthetic) function?

A

Pro-thrombin time (PT)

Also:
albumin, PTTK, Bilirubin
Enzymes (GGT, ALP, ALT, AST) only show location of damage not degree.

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22
Q

Clinical features of Chronic stable liver disease

A

Palmar erythema
Spider naevi (>5)
Dupuytren’s contracture
Gynaecomastia

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23
Q

Clinical features of portal HTN

A

Porto-systemic anastomoses

  • caput medusae
  • oesophageal varices
  • rectal varices

Splenomegaly
Scrotal oedema
Shifting dullness (ascites)

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24
Q

Clinical feature of decompensated liver failure

A

Hyperammonaemia

  • Flapping tremor
  • confusion

Jaundice (accumulation of bile salts)

Hepatic coma, death

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25
Role of Stellate cells in liver?
Store vitamin A Differentiate into myofibrobasts when there is damage to liver --> make collagen, form scars
26
Inflammatory adaptations in liver
Loss of microvilli Stellate cells activate Deposition of collagen (scar matrix) in space of Disse Loss of fenestrae - endothelial cells become continuous Result = blood does not interact with hepatocytes
27
Most important RF for hepatocellular carcinoma
Cirrhosis
28
Classification of chronic hepatitis
``` Grade = severity of inflammation Stage = severity of fibrosis ``` Stage more important than grade for prognosis.
29
What are mallory denk bodies?
Collapsed cytoskeleton in swollen hepatocytes | Present in EtOH hepatitis
30
Haemochromatosis pathogenesis
Mutation om Chr6 (HFe) | Increased GI iron absorption (with no way to excrete it)
31
Wilson's disease pathogenesis
Mutation on Chr 13 Often >1 mutation Failure of excretion of copper into bile by hepatocytes --> accumulation in liver, CNS
32
Tx for Wilson's disease
Zinc | Trientine
33
Histological Ix for Wilson' disease
Rhodanine stain - copper in hepatocytes (brown on blue counterstain)
34
Histology of alpha anti-trypsin 1 deficiency
Intra-cytoplasmic inclusions (misfiled protein) Macronodular hepatitis Cirrhosis
35
Macroscopic appearance of liver adenoma
Sharp demarcation
36
Most common type of liver malignancy?
Metastatic Receives blood from pancreas, stomach, large bowel etc. via portal circulation
37
Tumour marker for primary hepatocellular carcinoma?
Alpha foeto protein (AFP)
38
Associations with Primary cholangiocarcinoma
Primary sclerosis cholangitis (PSC) Worm infections (North Thailand) Cirrhosis
39
Cause of nutmeg liver?
Congestive heart failure
40
Hirschsprung's disease pathogenesis
Absence of ganglion cells from Auerbach (mesenteric) and Meissner (submucosal) plexus of rectum and distal colon. Uncoordinated peristalsis causes functional obstruction
41
Diagnostic Ix for Hirschsprung's
Full thickness rectal biopsy | - Hypertrophied nerve fibres but no ganglia
42
Locations of volvulus
``` Small bowel (infants) Sigmoid colon (elderly) ```
43
Definition of volvulus?
Complete twisting of loop of bowel at mesenteric base around vascular pedicle
44
Pathogenesis of diverticular disease
High intra-luminal pressure forces mucosa through 'weak points' of bowel
45
Most common location for diverticular disease
Left colon (90%)
46
Histology of pseudomembranous colitis
Macroscopic: - erytemaotus - 'wet cornflake' lesions (pseudomembranes)
47
most common vascular disorder of intestinal tract?
Ischaemic colitis / infarction
48
Usual location of ischaemic colitis / infarction
Watershed zones (where previous and next blood supply poorly overlap --> area with poor supply vulnerable to ischaemia) Splenic flexure - SMA, IMA Rectosigmoid - IMA, internal iliac artery
48
Usual location of ischaemic colitis / infarction
Watershed zones (where previous and next blood supply poorly overlap --> area with poor supply vulnerable to ischaemia) Splenic flexure - SMA, IMA Rectosigmoid - IMA, internal iliac artery
49
Causes of ischaemic colitis / infarction
Arterial occlusion - atheroma, thrombosis, embolism Venous occlusion - thrombus, hyper coagulable state Small vessel disease - DM, cholesterol emboli, vasculitis Low flow states - CCF, haemorrhage, shock Obstruction - hernia, intussusception, volvulus, adhesions
50
Key histological features of Crohn's
``` Mouth - anus Skip lesions Transmural inflammation Non caseating granulomas Sinus / fistula common ```
51
Key histological features of UC
``` Rectum + colon +/- mild 'backwash ileitis' and appendiceal involvement Continuous Mucosal inflammation only Shallow ulcers Bowel wall normal thickness ```
52
Complications of UC
Toxic megacolon Adenocarcinoma - 20-30x risk Severe haemorrhage
53
Complications of Crohn's
Fat wrapping Thick 'rubber hose' bowel wall, narrow lumen Linear ulcers, fissures Abscesses Adenocarcinoma (less than UC)
54
Derm manifestations of UC & Crohn's
Crohn's: Pyoderma gangrenosum, erythema multiforme, erythema nodosum UC: Pydoerma gangrenosum, erythema nodosum
55
Non Neo-plastic polyps
Hyperplastic - very common, no progression (for exam purposes) Inflammatory 'pseudopolyps' - areas of regenerating mucosa which project into lumen, seen in UC Hamartomatous - juvenile, Peutz-Jeghers
56
Neoplastic polyps
Tubular Tubulovillous Villous
57
Risk factors for cancer (from polyp)
Size - >4cm approx 45% invasive malignancy Proportion of villous component Degree of dysplastic change
58
Familial adenomatous polyposis - genetics & pathogenesis
Autosomal dominant Chromosome 5q21 - APC tumour suppressor gene Minimum 100 polyps (usually colorectal adenomatous) Virtually 100% develop ca. within 10-15 yrs
59
Garnder's syndrome - key features
Subtype of Familial adenomatous polyposis Distinct extra-intestinal features - multiple oestomas of skull, mandible - epidermoid cysts - desmoid tumours - dental caries, unerupted supernumerary death - post surgical mesenteric fibromatoses
60
Hereditary non polyposis colon cancer - genetics, pathogenesis
Autosomal dominant, uncommon Involves 1 of 4 DNA mismatch repair genes --> DNA replication errors Onset of colorectal ca. at early age
61
Type & distribution of cancer in HNPCC (Lynch syndrome)
high % proximal to splenic flexure Poorly differentiated + mutinous carcinoma more common + extracolonic cancer: endometrial, prostate, breast, stomach
62
Most common type of lower GI cancer
Adenocarcinoma - 98%
63
RF for Lower GI cancer
Diet - low fibre, high fat Lack of exercise, obesity Familial Chronic IBD
64
Tumour marker for lower GI cancer
Carcinoembryonic antigen (CEA)
65
Staging system for lower GI cancer
Duke's A = limited to mucosa ``` B1 = extending into muscular propria B2 = transmural invasion, no LN ``` ``` C1 = extending into muscular propria, LN involvement C2 = transmural invasion, LN involvement ``` D = distant mets
66
Layers of normal oesophagus
Epithelium Submucosa Muscular extra
67
Normal stomach - features of body
Lined by gastric mucosa columnar epithelium - foveolar, mucin secreting Specialised glands in lamina propria - produce acid, IF. Muscular mucosae No goblet cells!
68
Normal stomach - features of antrum
Lined by gastric mucosa columnar epithelium - foveolar, mucin secreting Non specialised glands in lamina propria - gastric pits Muscular mucosae
69
Normal duodenum features
Glandular epithelium with goblet cells - 'intestinal type' Villous architecture - villous:crypt ratio of >2:1
70
Features of acute oesophagitis
Neutrophils
71
Most common cause of acute oesophagitis
GORD / reflux
72
Barrett's oesophagus types
Without goblet cells - gastric type metaplasia With goblet cells - intestinal type metaplasia, more likely to progress to ca.
73
Barrett's oesophagus - basic process/pathogenesis
Squamous epithelium replaced by metaplastic columnar epithelium
74
Most common oesophageal ca.?
Adenocarcinoma (in 'developed' countries) Squamous cell carcinoma (in 'developing' countries)
75
Adenocarcinoma of oesophagus - key features
Associated with reflux Lower oesophagus Gland formation + mucin production (hallmarks of adenocarcinoma)
76
Squamous cell carcinoma of oeseophagus - key features
Associated with EtOH & smoking mid-lower oesophagus Keratin production (+ intercellular bridges)
77
Causes of oesophageal varices
Cirrhosis - most common | + portal vein thrombosis
78
Causes of acute gastritis
Chemical - aspirin, NSAIDs, alcohol, corrosives Infection - Helicobacter pylori
79
Causes of chronic gastritis
Autoimmune - anti-parietal Abs, mainly affects body of stmach Bacterial - H. pylori, affects antrum Chemical - NSAIDs, reflux, affects antrum
80
Biopsy finding in H. pylori infection
Gastric ulcer Chronic gastritis +/- acute activity
81
Complications of H. pylori infection
CLO-IM dysplasia Adenocarcinoma Lymphoma (MALToma)
82
Definition of ulcer
Defect through muscularis propria
83
Most common type of gastric cancer?
Adenocarcinoma (95%)
84
Morphological categories of gastric adenocarcinoma
Intestinal - well differentiated Diffuse - poorly differentiated (linitis plastica), includes signet ring cell carcinoma!
85
Other (non adenocarcinoma) gastric cancer types
Squamous cell carcinoma Lymphoma - MALToma Gastrointestinal stromal tumour (GIST) Neuroendocrine tumour
86
Pathogenesis of duodenitis
Increased acid production in stomach Spills over into duodeum Chronic inflammation, gastric metaplasia NOTE: once gastric type cells present, duodenum is vulnerable to H. Pylori
87
Causative organism of Whipple's disease
tropheryma whipellii | Rare bacterial infection seen in duodenum
88
Biopsy evidence of coeliac disease
Villous atrophy Crypt hyperplasia Increased intraepithelial lymphocytes (normal <20 per 100 enterocytes) NOTE: will only show this if currently eating gluten
89
Coeliac-associated cancer
In duodenum | T cell origin 'enteropathy associated T cell lymphoma' (EATL)
90
Functional cells of pancreas?
Acinar cells - produce enzymes - have abundant rough ER + Golgi
91
Definition of acute pancreatitis
Acute inflammation of pancreas | caused by aberrant release of pancreatic enzymes
92
Causes of acute pancreatitis
Duct obstruction - Gallstones - 50% - Trauma - fibrotic scarring, narrowing - Tumours - + EtOH Metabolic/toxic - Alcohol - 33% - Drugs e.g. thiazides - Hypercalcaemia - Hyperlipidaemia Poor blood supply - shock, hypothermia Infection - mumps Autoimmune Idiopathic - 15%
93
Pathophysiology of acute pancreatitis (from gallstones)
Gallstone stuck distal to where common bile duct + pancreatic duct join Reflux up pancreatic duct Damage to acini + release of pro-enzymes which become activated Activated enzymes cause acinar necrosis --> further enzyme release
94
Histology of fat necrosis in acute pancreatitis
Macroscopic: Necrosis forms free fatty acids Ca2+ ions bind to free fatty acids, forming soaps Seen as yellow/white foci Microscopic Blue = histological correlates of white/yellow foci
95
Pathophysiology of acute pancreatitis (due to EtOH)
Spasm/oedema of Sphincter of Oddi + formation of protein-rich pancreatic fluid Fluid obstructs pancreatic ducts
96
Patterns of injury in acute pancreatitis
Periductal - necrosis of acinar cells near ducts (obstruction) Perilobular - necrosis at edges of lobules (ischaemia) Panlobular - progressive periductal + perilobular damage
97
Causes of chronic pancreatitis
Metabolic/toxic - alcohol 80% - haemochromatosis Duct obstruction - gallstones - abnormal pancreatic duct - CF 'mucoviscoidosis' Tumours Autoimmune
98
Complications of chronic pancreatitis
Malabsorption Diabetes mellitus (late - neuroendocrine cells survive relatively well) Pseudocysts Increased risk of ca. of pancreas
99
Pancreatic pseudocyst - key features
Lined by fibrous tissue - not epithelial lining Contain fluid rich in pancreatic enzymes OR necrotic material Usually connect with pancreatic ducts
100
Possible outcomes of pancreatic pseudocyst
Perforate Become infected Compress adjacent structures Resolve
101
Key features of Autoimmune pancreatitis
Large no. of IgG4 + plasma cells Involves pancreas, bile ducts + almost any other body part
102
Most common pancreatic neoplasm?
Ductal carcinoma - 85%
103
Risk factors for pancreatic ductal carcinoma
Smoking BMI, dietary factors Diabetes Chronic pancreatitis
104
Pathogenesis of pancreatic ductal carcinoma
Arise from dysplastic lesions - pancreatic intraductal neoplasms (PanIN) - intraductal mucinous papillary neoplasm K-Ras mutation in 95%
105
Tumour marker for pancreatic ductal carcinoma
Carbohydrate antigen 19-9 (CA19-9)
106
Distribution of pancreatic ductal carcinoma
Head 60% - may present earlier due to obstruction of biliary tree Body Tail Diffuse
107
Histology of pancreatic ductal carcinoma
Adenocarcinoma so mucin production + glands Set in desmoplastic stroma (storm that arises in response to cancer - fibrous reaction) Perineural invasion - characteristic
108
Pancreatic endocrine neoplasms - key features
Usually NON secretory But can release glucagon, insulin etc. Difficult to predict behaviour. May be associated with MEN 1
109
Most common secretory tumour
Insulinoma
110
Risk factors for gallstones (cholelithiasis)
Increase age 'forty' Female Ethnicity & geography - Native American Hereditary disorders of bile metabolism Drugs - COCP Acquired disorders - rapid weight loss (increased excretion of lipids)
111
Pigment gallstones - characteristics
Contain calcium salts of unconjugated bilirubin Multiple Mostly radio-opaque
112
features of chronic cholecystitis
Chronic inflammation - lymphocytes Fibrosis Thickened wall (normal <2mm) Diverticula e.g. Rokitansky-Aschoff sinuses 90% associated with gallstones
113
Most common cause of gallbladder ca.
Gallstones - 90% associated