Organ Pathology Flashcards
(129 cards)
1
Q
Transaminase tests
A
AST and ALT
Elevation = hepatic inflammation and hepatocellular injury
2
Q
GGT and ALP tests
A
Elevation = cholestasis
Bile stasis/obstruction
3
Q
Bilirubin test
A
Elevation = jaundice
Due to biliary obstruction or hepatocellular injury
4
Q
Albumin and clotting factor tests
A
Abnormal = impaired synthesis by liver
5
Q
Risk factors for Hepatitis C
A
Injecting drug use Unscreened blood and donated organs Sexual transmission Mother to baby Occupational Tattoos
6
Q
Hepatitis C treatment
A
Used to be interferon based. Suboptimal cure rates, problematic side effects, long duration
Now, direct acting antivirals taken as short course of tablets with better cure rates
7
Q
Portal hypertension
A
High pressure in portal vein
Difficult for blood in portal circulation to return to right heart so porto-systemic collaterals can form to try and divert blood from portal circulation back to right heart - varices formation
8
Q
3 causes of portal hypertension
A
Pre-hepatic: portal vein thrombosis
Intra-hepatic: cirrhosis
Post-hepatic: hepatic vein thrombosis or right sided heart failure
9
Q
Hepatic encephalopathy
A
Result of chronic liver failure Liver can't detoxify substances produced by bacterial metabolism causing ammonia build up which can pass blood brain barrier Mood and personality change Inverted sleep patterns Confusion Bizarre behaviour Drowsiness Coma
10
Q
HE treatment
A
Lactulose
Type of laxative which seems to decrease ammonia generation by bacteria and convert it to a non-absorbable molecule
Not curative
11
Q
Ascites
A
Fluid in peritoneum causing abdominal distension
Caused by portal hypertension among other things
Increased hydrostatic pressure, decreased oncotic pressure
12
Q
Budd-Chiari syndrome
A
Acute thrombosis of hepatic veins
Outflow of blood from liver is obstructed
Liver becomes acutely congested causing hepatocellular damage
Portal hypertension occurs, ascites develops
13
Q
Budd-Chiari causes
A
75% no obvious cause
25% tumour, pregnancy, oral contraceptive, clotting disorders
14
Q
Budd-Chiari management
A
Portocaval shunting to divert blood flow
Anticoagulation
Diuretics
15
Q
5 general responses of hepatic injury
A
Intracellular accumulation Cell death Inflammation Regeneration Fibrosis
16
Q
Hepatic failure
A
Sudden massive destruction or endpoint of chronic damage
Have to lose over 80% capacity for functional loss
17
Q
Signs of hepatic failure
A
Jaundice
Hypoalbuminaemia
Increased ammonia = HE
18
Q
Cirrhosis mechanism
A
Activated stellate cells cause myofibroblast proliferation and fibrogenesis
Activated Kupffer cells release cytokines
Cytokines induce inflammation causing hepatocyte dysfunction and death
19
Q
Fibrosis mechanism
A
Proliferating hepatocytes encircled by fibrosis = parenchymal nodules
Formation of these nodules disrupts architecture of liver
Shunts formed, PV and HA blood bypasses functional liver cells causing progressive fibrosis
20
Q
4 consequences of portal hypertension
A
Ascites
Portosystemic shunts
Congestive splenomegaly
Hepatic encephalopathy
21
Q
Hepatitis A
A
Benign, acute, mostly asymptomatic
Faecal-oral transmission
Can cause mild illness and jaundice
22
Q
Hepatitis B
A
Chronic or acute
Blood and body fluid borne
Immune response to viral antigens on infected hepatocytes leads to liver cell damage
23
Q
Drug and toxin induced liver injury
A
Either predictable or unpredictable hepatotoxins
Cholestasis, hepatocellular necrosis, fatty liver, fibrosis, granulomas, vascular lesions, neoplasms
Acute = likely to be paracetamol
Chronic = likely to be alcohol
24
Q
Alcoholic liver disease
A
Changes in lipid metabolism, decreased export of lipoproteins and cell injury caused by ROS and cytokines leads to hepatic steatosis, alcoholic hepatitis and cirrhosis
25
Metabolic liver disease
Also known as non-alcoholic fatty liver disease
Associated with obesity and related illnesses
Initially only hepatic steatosis, then steatosis and inflammation, then cirrhosis
26
Haemochromatosis
Excessive accumulation of body iron deposited in liver and pancreas
Autosomal recessive
27
Cholestasis of sepsis
Infection, ischaemia or circulating microbial products can cause widespread inflammation stopping bile from flowing out of liver
28
Autoimmune cholangiopathies
Primary biliary cirrhosis (destruction of bile canaliculi) and primary sclerosing cholangitis (destruction of bile ducts)
29
2 types of benign liver tumour
Cavernous haemangioma
| Hepatocellular adenoma
30
4 types of malignant liver tumour
Hepatocellular carcinoma
Hepatoblastoma
Cholangiocarcinoma
Hepatic metastases
31
5 causes of jaundice
Haemolysis
Gilberts syndrome
Cholestasis
Liver obstruction (internal or external)
32
ALP
Alkaline phosphatase
Hydrolyses phosphate groups
Found in liver, bone, intestine, placenta and some tumours
>600 units per litre considered pathological
High in gallstones and tumours
33
GGT
```
Gamma-glutamyl transferase
Mostly biliary (liver)
Elevated in inflammation/obstruction of biliary system, also drugs and alcohol
```
34
ALT
```
Alanine aminotransferase
Normal concentration <45 units per litre
Found mostly in hepatocyte cytosol
Key for gluconeogenesis
Elevated in hepatitis
```
35
AST
Aspartate transaminase
Key for gluconeogenesis
Found in hepatocyte cytosol and mitochondria
Less liver specific and shorter half life than ALT
Elevated in hepatitis
36
Albumin
Normal concentration 35 - 47 g/L
Found in liver
Decreases due to cirrhosis, over excretion by kidneys, illness and redistribution
37
Globulins
Reflect inflammation
| Elevated in chronic hepatitis and cirrhosis
38
Prothrombin
Reflects clotting factor synthesis
| Elevation due to vitamin K deficiency or liver failure
39
Glucose
Liver maintains fasting blood glucose
| Inability to maintain glucose indicates serious disease
40
Enzymatic signs of scarring and declining function
Increased GGT and ALP
Increased AST/ALT ratio
Increased globulins, bilirubin, ammonia and prothrombin
Decreased albumin and glucose
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CEA
Carcinoembryonic antigen
Indicates cancer or cirrhosis, hepatitis, ulcerative colitis, smoking
>20 ng/mL indicates malignant cancer
42
Gilberts syndrome
Bilirubin levels high, other tests normal
Worsens after illness, fasting or alcohol
Persistent mild jaundice
Normally diagnosed by making patient fast for 48 hours. If bilirubin rises to more than double normal, Gilberts assumed
43
Most common causes of liver failure test abnormalities
Fatty liver
Viral hepatitis
Alcohol
Haemochromatosis
44
Acute pancreatitis
Inflammation of the pancreas associated with acinar cell injury
Autodigestion by pancreatic enzymes
Cell injury response mediated by inflammatory cytokines
Caused by obstruction or direct injury to acinar cells
45
Main categories of acute pancreatitis and their most common causes
Metabolic - alcohol
Mechanical - gallstones and trauma
Vascular - shock and vasculitis
Infection - mumps
46
Enzyme release in acute pancreatitis and the consequences
Protesases - proteolytic destruction of acini, ducts and islets
Lipases - fat necrosis
Elastases - blood vessel destruction leading to interstitial haemorrhage
Cell injury response - inflammation, oedema, impaired blood flow, ischaemia
47
Pancreatic obstruction in acute pancreatitis
Mainly by gallstones and ductal concretions in alcoholics
Increased intrapancreatic ductal pressure
Accumulation of enzyme rich interstitial fluid
Fat necrosis
Oedema and inflammation leading to compromised blood flow
48
Primary acinar cell injury in acute pancreatitis
Secondary to viruses, drugs, trauma and ischaemia
| Releases enzymes
49
Clinical features of acute pancreatitis
Epigastric pain
Nausea and vomiting
Fever and tachycardia
Abdominal tenderness - in rare cases ileus and shock
50
Diagnosis of acute pancreatitis
High white cell count
Elevated serum amylase (lipase)
CT to look for oedema, necrosis and pseudocysts
Laparotomy (rare)
51
Management of acute pancreatitis
Rest the pancreas and close monitoring
IV fluids
Analgesia
52
Complications of acute pancreatitis
```
Hypotension
Shock
Renal and respiratory failure
Low calcium, hyperglycaemia and jaundice
Pseuodocysts
```
53
Chronic pancreatitis
Repeated bouts of inflammation with loss of parenchyma and replacement by fibrous tissue
Often due to heavy alcohol intake causing intraductal plugs of protein and cell debris
Also previous acute pancreatitis, severe malnutrition and CFTR mutations
Atrophy of exocrine compartment but islets relatively unaffected
54
Clinical features of chronic pancreatitis
```
Repeated attacks of abdominal pain often brought on by alcohol - can be more persistent
If ongoing, loss of exocrine function causing malabsoprtion, pseudocysts
Diabetes mellitus (rare)
```
55
Diagnosis of chronic pancreatitis
```
CT
Serum amylase (not entirely accurate)
```
56
Pancreatic carcinoma
Poor prognosis. Whipples procedure performed in 15-20% cases
Common in smokers, alcohol and coffee suggested but not confirmed
If in the head, invades ampulla causing biliary obstruction
If in the tail, neck or body, silent and metastatic
57
Clinical features of pancreatic carcinoma
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Obstructive jaundice
Pain
Weight loss
Pancreatitis
Thrombophlebitis
```
58
Cholelithiasis
Gallstones
Mostly silent
Most are cholesterol based (yellow/green)
Remainder are bilirubin/calcium salts (brown/black)
59
Cholesterol stones
Bile supersaturated with cholesterol. Conditions favour crystal formation. Cholesterol crystals remain in gallbladder long enough for stones to form (cholestasis)
60
Risk factors for cholelithiasis
Increased age and female
Oral contraceptives, pregnancy, obesity, rapid weight loss
Gallbladder stasis
Family history
61
Risk factors for pigment stones
Chronic haemolytic syndromes
| Bacterial infection of biliary tree
62
Clinical consequences of gallstones
Mostly asymptomatic
Cholecystitis
Biliary colic
63
Clinical features of cholecystitis
Right upper quadrant abdominal pain and tenderness with fever
Neutrophil leukocytosis
Elevated bilirubin, ALP and GGT
DIagnosed by ultrasound
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Acute cholecystitis
Most causes precipitated by gallstones
Obstruction of neck of gallbladder or cystic duct
Chemical irritation followed by bacterial infection
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Chronic cholecystitis
Long term association of gallstones and low grade inflammation
Gallbladder often contracted with thickened wall
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Management of cholecystitis
Initially - can settle with conservative therapy such as IV fluids and analgesia but can require acute surgical intervention
Long term - laparoscopic cholecystectomy
67
Choledocholiathis
Presence of stones in the biliary tree
Can lead to biliary obstruction with colicky abdominal pain and obstructive jaundice
Cna also lead to pancreatitis and cholangitis
68
Carcinoma of the gallbladder
Late presentation, poor prognosis
Older, female patients
Increased with gallstoned and chronic infections
Most are adenocarcinomas, rarely squamous or mixed
Most have invaded liver by time of diagnosis
69
Carcinoma of extrahepatic bile duct
Uncommon adenocarcinomas that may involve the ampullary region
Often present with slowly progressive obstruction of bile duct causing jaundice, pale stools, weight loss and nausea
70
Polyp
Circumscribed growth or tuour which projects above surrounding mucosa
Can be neoplastic or non-neoplastic
Majority occur sporadically in the colon and increase in frequency with increasing age
Some people prone to developing large numbers of polyps due to polyposis syndromes
71
Non-neoplastic polyps
Result of abnormal mucosal maturation, inflammation or hyperplasia
72
Neoplastic polyps
Result of proliferation and dysplasia
Called adenomatous polyps
Precursors of carcinoma
73
Sessile
Unbranched, immobile
74
Pedunculated
Branched, somewhat mobile
75
Hyperplastic polyps
Non-neoplastic
| Benign, asymptomatic, small and sessile
76
Juvenile polyps
Non-neoplastic
Common in children
Usually occur in rectum and present with rectal bleeding
Composed of abundant inflamed lamina propria containing cystically dilated glands
77
Inflammatory polyps
Non-neoplastic
Often seen in IBD and Crohns
Benign pseudopolyps
78
Adenomas
Neoplastic
Familial
Can be sessile or pedunculated
Classified as tubular, villous or tubulovillous
79
Malignant risk factors of polyps
Polyp size - the bigger the polyp, the more cells vulnerable to changes
Architecture - villous
Severity of dysplasia
80
FAP
Familial adenomatous polyposis syndrome
Hundreds of adenomas, first appearing in teens/early twenties
Normally develop into cancer within 10-15 years
Genetic defect in APC gene on chromosome 5
81
Adenoma-carcinoma sequence
Normal epithelium
-----> Loss/mutation of APC locus on chromosome 5
Hyperproliferative epithelium
-----> Loss of DNA methylation
Early adenoma
-----> Mutation of ras gene on chromosome 12
Intermediate adenoma
-----> Loss of tumour suppressor on chromosome 18
Late adenoma
-----> Loss of p53 gene on chromosome 17
Carcinoma
82
Colorectal carcinoma
Most are sporadic, some have underlying genetic component (hereditary non-polyposis carcinoma of the colon, HNPCC)
Younger patients tend to have FAP or ulcerative colitis
High red meat and carb intake, low vegetable intake
Can occur anywhere in colon but rare in small intestine
Can be well, moderately or poorly differentiated
83
Dukes staging system of colorectal carcinoma
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A = tumour protrudes submucosa or muscularis externa
B = tumour protrudes into serosa
C = tumour protrudes through serosa into body caivty and infects nodes
```
84
TNM staging system of colorectal carcinoma
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T = Extent of invasion through bowel wall
N = number of lymph nodes involved
M = metastatic presence
```
85
4 rare tumours of the colon
Carcinoid - endocrine cell tumours
Lymphoma - primary blood cancer causes secondary bowel cancer
Anorectal - dominated by squamous cell carcinomas
Mesenchymal - gastrointestinal stromal tumours and lipomas
86
Courvoisiers sign
Palpable gallbladder
| Often present in cases of prolonged biliary obstruction
87
Cystic fibrosis in pancreatic disease
Decreased function of CFTR gene prevents Cl- secretion. To neutralise, Na+ and H2O stay inside cell
Secretions are sticky and clog passages causing decreased lung function and increased susceptibility to lung infection
Cl- accumulates in ductal cells in the pancreas. Same thing happens here causing sticky mucus, blocked passages and blocked enzymes
88
Diarrhoea
>200 g/day
| Loose consistency, frequent
89
Acute diarrhoea
Up to 14 days
Infection (viruses most common)
Can cause inflammatory, omsotic or secretory diarrhoea
90
Chronic diarrhoea
More than 14 days
| Inflammatory, osmotic, secretory or fatty
91
Campylobacter diarrhoea
Inflammatory
Acute
Caused mucosal inflammation causing increased exudate
92
Giardia diarrhoea
Osmotic
Acute
Mild villous atrophy leads to carbohydrate malabsoprtion
Undigested sugars are osmotically active which draws fluid in
93
Enterotoxigenic E. coli diarrhoea
Secretory
Acute
Toxins stimulate excessive fluid secretion
94
Chronic inflammatory diarrhoea causes
IBD
Diverticulitis
Small intestinal bacterial overgrowth causing direct inflammation of enterocytes
95
Chronic osmotic diarrhoea causes
Carbohydrate malabsoprtion
Coeliac
Small intestinal bacterial overgrowth causing malabsorption of osmotically active by-products of bacteria metabolism
Laxative abuse
96
Chronic secretory diarrhoea causes
Terminal ileal resection causing bile acid malabsorption
Chloecystectomy causing continuous bile flow into the small intestine
IBD
Diverticulitis
Small intestinal bacterial overgrowth causing unabsorbed food products and bile acids to stimulate secretory colon cells
Disordered motility
Laxative abuse
97
Chronic fatty diarrhoea causes
Pancreatic exocrine insufficiency
Bile acid malabsorption
Small intestinal bacterial overgrowth causing deconjugation of bile acids leading to impaired micelle formation and impaired fat digestion and absorption
Coeliac
Short bowel syndrome (not enough mucosal surface)
98
SIBO
Small intestinal bacterial overgrowth
Excess colonic bacteria in small intestine casuing bloating, flatulence, discomfort, malabsoprtion and steatorrhoea
Predisposed by impaired motility, anatomic disorders, metabolic and immune diseases
99
Diarrhoea in SIBO
Inflammatory: bacteria inflames enterocytes
Osmotic: Malabsorption of osmotically active byproducts of bacteria metabolism
Secferotry: Unabsorbed food and bile stimulates secertory cells
Fatty: Deconjugated bile acids causes impaired micelle formation therefore impaired fat digestion and absoprtion
100
Functional gut disorders
```
No structural or tissue abnormality
Disturbed motility
Visceral hypersensivity
Brain-gut dysfunction
Psychosocial factors
Can affect any part of the gut
```
101
Oesophageal functional gut disorders
Globus
| Functional heartburn
102
Stomach functional gut disorders
Functional dyspepsia
| Fucntional vomiting
103
Bowel functional gut disorders
Irritable bowel
| Functional abdominal pain
104
IBS
Swinging bowel
Abdominal pain relieved with bowel movement
May occur after gastroenteritis
Symptoms include urgency, bloating, flatulence, fatigue, poor sleep
105
Alarm symptoms
```
If present, serious pathology should be considered
Nocturnal diarrhoea or pain
Rectal bleeding
Anaemia and iron deficiency
Weight loss
Vomiting
Being over 50
Family history of colon cancer
```
106
Altered gut motility in in IBS
Can increase and decrease
| Exaggerated response = diarrhoea, reduced response = constipation
107
Visceral hypersensitivity in IBS
Sufferers tend to perceive distension more than normal and describe it as painful or unpleasant rather than just uncomfortable
108
Peripheral sensitisation in visceral hypersensitivity
Symptoms sometimes start after an episode of gastroenteritis. Previous tissue inflammation or injury may upregulate sensitivity and excitability of nociceptors leading to hyperalgesia and allodynia
109
Central sensitisation in visceral hypersensitivity
Peripheral sensitisation may lead to surrounding uninjured tissue to become hypersensitive as well leading to global sensitisation throughout the body
110
Gate control theory
Spinal cord has a method of controlling pain signals. Hypervigilance of gate control can lead to brain focusing on processing unpleasant stimuli
Tends to increase with stress
111
Treatment of IBS
```
Multidisciplinary approach
Conventional treatments (laxatives, fibre supplements, TCAs and anti-motility drugs) with dietary exclusions, probiotics and psychological therapies
```
112
Ulcerative colitis pathology
Continuous in the colon, begins in the rectum and spreads proximally
Diffuse and granular mucosal inflammation but doesn't involve other gut layers
Rarely macroscopic ulceration
113
Ulcerative colitis histology
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Mucosal inflammation
Crypt branching and atrophy
Crypt abscess
Loss of goblet cells
Paneth cell metaplasia
```
114
Ulcerative colitis clinical signs
Bloody diarrhoea
Frequent and urgent bowel movements
Abdominal discomfort
Fever, malaise, weight loss
115
Toxic megacolon
Progressive dilation causing muscular paralysis which decreases peristalsis - can lead to perforation
116
Crohns pathology
Can be in any part of the GI tract but most commonly the colon and ileum
Discontinuous skip lesions
Transmural inflammation
117
Transmural inflammation
Common in Crohns
Starts as small ulcers on mucosa and progresses to deep penetrating ulcers with fissuring, showing a cobblestone appearance
118
Crohns histology
Transmural inflammation across the entire depth of the intestine wall
Non-caseating and non-necrotising granulomas
119
Granuloma
Activated macrophages fuse together to make a giant cell which can group together in an area of inflammation
120
4 clinical subtypes of Crohns
Inflammatory
Structuring
Fistulising
Perianal
121
Inflammatory Crohns
Colitis - bloody diarrhoea
Ileitis - abdominal pain, malabsorption leading to watery or fatty diarrhoea
Gastritis and duodenitis - dyspepsia
122
Stricturing Crohns
Initially inflammatory due to oedema but becomes fibrotic due to scarring
Causes abdominal pain and distension, vomiting and decreased bowel movements
123
Fistulising Crohns
Inflammation penetrates gut wall and goes through adventitia or serosa. Becomes sticky and moves into wall of neighbouring tissue
Can be enterocutaneous, enteroenteric, enterocolic or rectovaginal
124
Perianal Crohns
Perianal fistulas occur which can get infected and become perianal abscesses
Anal fissures
125
General treatment of IBD
5-ASAs
Steroids
Immunosuppression
Monoclonal antibodies
126
Surgery in IBD
Colectomy can cure ulcerative colitis and help Crohns but no definitive treatment for Crohns
Can treat complications such as bowl obstruction, perforation, fistula, abscess
127
Genetics of Coeliac disease
Incomplete dominance
Two susceptibility genes: HLA-DQ2 and HLA-DQ8
HLA-DQ2.5 carriers will get coeliac
HLA-DQ2.2 carriers might get coeliac
HLA-DQ8 carriers generally need another allele to get coeliac
Populations without HLA-DQ2 (e.g. Asian populations) don't get coeliac disease
128
Pathology of Coeliac disease
Gluten exposure required
Villous atrophy and crypt hypertrophy
Loss of brush border enzymes and loss of stimulus for pancreatic and bile secretion
129
Coeliac antibodies
Anti-TTG IgA mucosal antibodies for treatment
Some sufferers have IgA deficiency therefore IgG form of antibodies needed instead
Diagnosed with a combination of blood test for tissue transglutaminase antibody and biopsy to check for villous atrophy
