Gastrointestinal and Liver Flashcards
1
Q
WHAT IS HEPATITIS?
A
Hepatitis refers to an inflammatory condition of the liver. It’s commonly caused by a viral infection, but there are other possible causes of hepatitis. These include autoimmune hepatitis and hepatitis that occurs as a secondary result of medications, drugs, toxins, and alcohol
2
Q
What are common hepatitides for each of these hepatitis?
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Yellow fever
A
Epstein-Barr V
Cytomegalovirus
Toxoplasma
Influenza
Adenoviruses
Coxsackie B
3
Q
What is the route of transmission for each of the hepatitis’?
A
A Faeco-oral.
B blood/ sexual.
C Blood/ sexual.
D Blood/ sexual
E Faeco-oral.
4
Q
Is there chronic infection in each of the hepatitis’?
A
A No
B Yes
C Yes
D Yes
E No
5
Q
How can you prevent each of the hepatitis’?
A
A Pre and post-exposure immunisation.
B Pre and post-exposure immunisation. Behaviour modification.
C Blood donor screening. Behaviour modificationtion.
D HBV immunisation. Behaviour modification.
E Clean drinking water.
6
Q
What are the symptoms of acute hepatitis?
A
Malaise
Myalgia
Fever
Nausea/vomiting
Jaundice
RUQ pain.
7
Q
What are the different levels of these in acute hepatitis?
AST
ALT
Alk Phos
Albumin.
Bilirubin.
A
AST (aspartate transaminase) raised
ALT (alanine transaminase) raised
Alk Phos same or raised
Albumin lower or same
Bilirubin raised.
8
Q
What is a typical case history for hep A?
A
Travelled to Malaysia for
- stayed in hostels, local food
- ‘sea-food banquet’
Unwell 3 weeks after return to UK
- headache
- lethargy
- aching all over
- poor appetite
- hot and cold 10/7
later notices eyes/skin yellow
9
Q
What is the name for hep A?
A
PicoRNAvirus.
10
Q
Where is hepatitis A found?
A
Contaminated food or water.
Shellfish
Travellers.
Infected food handlers.
Close personal contact.
Household.
Sexual.
Childcare groups.
Blood - IVDU.
11
Q
When does ALT and AST rise in hep A? When do they return back to normal?
A
Within 1 month. 2 months.
12
Q
When does IgM anti-HAV show an increase in hep A? When is IgG detectable?
A
2-4 months. For life.
13
Q
What is the hep A vaccination?
A
Inactivated hepatitis A virus
Grown in human diploid cells
Dose - 0.5ml im - repeat at 6-12 months - booster every 10 years
HAV immunoglobulin - post exposure prophylaxis.
14
Q
When do you notice a rise in IgM anti-HBc in hep B?
A
From 8-24 weeks.
15
Q
What is a typical case for Hep B?
A
Divorced
- new partner for last 8/12
- Egyptian
Feeling tired ‘long time’
Noticed eyes yellow 5 days ago
Skin very yellow last 24 hours
Urine ‘dark orange’
Afebrile (no fever)
Tender hepatomegaly
Mild pitting oedema of ankles
Arthralgia (pain in joints) and urticaria (skin rash) are commoner.
16
Q
What would be found out from the investigations for hep B?
A
USS abdo:
- enlarged liver, bright echogenic texture
- no focal abnormality
17
Q
When do anti-HBs start being produced in hepatitis B? What antigens are produced when?
A
After 32 weeks.
HBSAg (surface antigen) is present 1–6 months after exposure.
HBeAg (e antigen) is present for 11⁄2–3 months after acute illness and implies high infectivity.
HBSAg persisting for >6 months defines carrier status.
18
Q
What are the serology results for acute hepatits B?
A
19
Q
What would you find in a chronic hep B sufferer?
A
A high hep B surface antigen (HBsAg) (Australian antigen).
Total anti-HBc is also high.
20
Q
What is the serology for a chronic hepatitis B suferer?
A
21
Q
What is Hep B called?
A
Hepadnavirus.
22
Q
Where does hep B replicate?
A
Hepatocytes.
23
Q
What happens in a hep B infection?
A
incubation 6 week to 6 months
May be asymptomatic - esp <5 yrs
Symptoms can last 6-12 weeks
>90% adults will clear infection
<50% children <5 yrs will clear infection
24
Q
What are the facts of chronic hep B infection?
A
<50% adults develop chronic infection
- HBsAg >6/12
Highly infectious
- HBeAg +ve
2% carriers / year clear infection and develop natural immunity
- female>male
25
What is the hep B vaccine types?
Inactivated HBsAg
Recombinant DNA (biosynthetic)
Dose: 1ml
- 3 doses at 0, 1 and 6/12
- booster every 5 years
- accelerated course 0, 1, 2/12
HBV immunoglobulin - post-exposure prophylaxis
26
What is the hep B treatment?
Alpha Interferons
Nucleoside Analogues
**_Tenofovir_**
**_Entecavir_**
27
What are the different serologies for acute, previous, chroic low infectious and chronic high infectious?
HBcAb
HBsAb
HBeAb
HBsAg
HBeAg
28
What is the typical case for hep C?
Intravenous drug use for 12 yrs
- heroin +/- crack cocaine
- often shared ‘works’
- smokes cannabis ‘occasionally’
In rehab for 6/12
- not injected 5/12
- attended for health check
29
What would you find on examination of Hep C patient? Also Serology?
Underweight
Scars both arms and groins
Not jaundiced
Afebrile
Tender liver edge.
30
What are the tests for hep C?
LFT (AST:ALT \<1:1 until cirrhosis develops)
anti-HCV antibodies confirms exposure;
HCV-PCR confirms on-going infection/chronicity;
liver biopsy if HCV-PCR +ve to assess liver damage and need for treatment.
31
What is hep C called?
Flavivirus (RNA).
32
What happens in hep C patients, what percentage have acute and chronic?
Acute hepatitis ~20% patients
- majority asymptomatic
- incubation 2-26/52
Chronic hepatitis ~ 80%
cirrhosis 15%
hepatocellular carcinoma 5%
33
How is Hep C characterised in the liver?
Lymphocytic inflammation.
34
What is the serology like in a hep C patient?
* *_HCV Ab_**
- in all patients
- appears up to 4/52 after infection
* *_HCV RNA_**
- detected by PCR
- present in chronic infection
No vaccine available.
35
What is the hep C treatment?
**_Pegylated Interferons_**
Weekly injections
**_Ribavirin_**
Tablets
Newer drugs (eg Sofofbuvir)
36
How can you prevent hep C?
Screening blood products
Lifestyle modification - needle exchanges etc
Universal precautions - for handling all bodily fluids
37
What is hep D?
Co-infection with acute HBV
- increased severity of infection
Super-infection in patients with chronic HBV
- 2o acute hepatitis
- increases risk of fulminant hepatitis
- increased progression of liver disease
38
What are the tests and treatments for hep D?
Anti-HDV antibody
As interferon-alpha has limited success, liver transplantation may be needed.
39
What is hep E?
Small RNA virus
Similar to Hep A
- acute hepatitis
- no chronic disease
Less infectious
Increased mortality 1-2%
- pregnant women 10-20%
now endemic in UK
40
What one of the hepatitis' is DNA?
Hepatitis B
41
WHAT DOES THE LIVER DO?
Glucose and fat metabolism.
Detoxification and excretion.
- bilirubin
- ammonia
- drugs / hormones / pollutants
Protein synthesis.
- albumin
- clotting factors
Defence against infection.
42
How is the liver arranged? How does the blood flow through it?
Regular way (acing or lobular models).
Blood enters via the portal vein and hepatic artery, which lie together with a small bile duct within the portal tract.
Blood flows into a system of sinusoids which bathe the liver cells arranged in plates, with blood, before exiting via the hepatic vein.
43
How many zones does the liver have?
Three, each receiving progressive less oxygenated blood.
44
What are the types of liver injury? What can they lead to?
Acute and chronic.
45
What does acute liver injury lead to?
Results in damage to and loss of cells.
Cell death may occur by necrosis (associated with neutrophils).
Or apoptosis.
46
What does chronic liver injury lead to?
Leads to fibrosis, termed cirrhosis in severest form.
47
What can cause acute liver injury?
Viral (A,B, EBV).
Drug.
Alcohol.
Vascular.
Obstruction.
Congestion.
48
What can cause chronic liver injury?
Alcohol.
Viral (B,C).
Autoimmune.
Metabolic (iron, copper).
49
How does acute liver injury present?
malaise, nausea, anorexia, jaundice
rarer:
- confusion
- bleeding
- liver pain
- hypoglycaemia
50
How does chronic liver injury present?
Ascites
Oedema
Haematemesis (varices)
Malaise
Anorexia
Wasting
Easy bruising
Itching
Hepatomegaly,
Abnormal LFTs rarer: - jaundice - confusion
51
What are some serum 'liver function tests'?
Serum bilirubin, albumin, prothrombin time:
Serum liver enzymes:
- cholestatic: alkaline phosphatase, gamma-GT
- hepatocellular: transaminases (AST, ALT)
(give no index of liver function)
| (give some index of liver function)
52
What are the different types of jaundice? Where are they seen?
•Unconjugated - “pre-hepatic”
- Gilberts, Haemolysis
•Conjugated – “cholestatic”
- Liver disease “hepatic”
- Bile duct obstruction “post hepatic”
53
Compare pre hepatic and hepatic or post hepatic for these. Urine. Stools. Itching. Liver tests.
Urine. Normal Dark.
Stools. Normal May be pale.
Itching. No Maybe.
Liver tests. Normal Abnormal.
54
What are some causes of liver disease?
Hepatitis - Viral - Drug - Immune - Alcohol
Ischaemia
Neoplasm
Congestion (CCF).
55
What are some causes of obstruction?
Gallstone
- Bile duct
- Mirizzi
Stricture
- Malignant
- Ischaemic
- Inflammatory
Blocked stent
56
What liver tests would tell you which jaundice it is? What further tests could be done?
Liver enzymes: Very high AST/ALT suggests liver disease, some exceptions
Biliary obstruction: 90% have dilated intrahepatic bile ducts on ultrasound
Need further imaging:
CT
Magnetic resonance cholangioram MRCP
Endoscopic retrograde cholangiogram ERCP
57
What are the different types of drug induced liver injury?
Hepatocellular.
Cholestatic.
Mixed.
58
What drugs are known to have drug induced liver injury?
Antibiotics.
CNS drugs.
Immunosuppresents.
Analgesics/musculoskeletal.
Gastrointestinal drugs.
Dietary supplements.
Multiple drugs.
59
WHAT HAPPENS IN PARACETAMOL POISONING?
Paracetamol conveyed by Cy P450 into reactive intermediate and then into cellular macromolecules which causes cellular necrosis.
60
What is needed to help paracetamol poisoning? What does it do?
Start N-acetylcystine.
Increases Reactive intermediate to stable metabolite conversion.
Increases glutathione transferase activity.
61
What does N-acetylcystine correct?
coagulation defects
- fluid electrolyte and acid base balance
- renal failure
- hypoglycaemia
- encephalopathy
62
What are some paracetamol induced liver failure poor prognosis indicators?
Late presentation
Acidosis
Prothrommbin time \> 70 sec
Serum creatinine ≥ 300 µmol/l
Consider emergency liver transplant - otherwise 80% mortality
63
WHAT ARE GALLSTONES MADE UP OF?
70% cholesterol, 30% pigment(mainly bilirubin) +/- calcium.
Pigment stones:
Small.
Causes: haemolysis.
Cholesterol stones:
Large.
Causes: gender, age, obesity
Mixed stones: Faceted (calcium salts, pigment, and cholesterol).
64
What is the prevalence of gallstones?
8% of those over 40yrs.
90% remain asymptomatic.
Risk factors for stones becoming symptomatic: smoking; parity.
65
What are some risk factors for gallstones?
Female
Fat
Forty
Fertile.
66
WHAT IS CHOLECYSTITIS?
Stones or sludge in the neck of the gallbladder or cystic duct.
Causing inflammation of the gall bladder.
67
What happens when somebody eats some food containing a lot of fat?
The small intestine secretes CCK which travels in the blood to cause the gallbladder to contract and release bile.
68
What is the pathology of cholecystitis?
Stone stuck in cystic duct
Causes stretching out of gall bladder
Irritates nerves around the gall bladder (pain)
Bile stays in gall bladder causing release of mucus and inflammatory mediators
Results in inflammation and pressure increase
Bacteria start to build up
Pressure builds up and bacteria go through wall causing peritonitis (rebound tenderness)
Immune system starts response with neutrophils
69
What things can happen with a stone in the cystic duct?
Stone falls back out the cystic duct back into the gall bladder
OR
Stone stays stuck causing ballooning of gall bladder
Pressure on blood vessels and gangrenous cell death
Could rupture
OR
Stone gets stuck further down
Bile backs up into liver
Bile forces between tight junctions into blood
Increase in serum conjugated bilirubin
Jaundice
ALP from bile cells leaks because they die
70
What bacteria start to build up in the gut?
E. Coli
Enterococci
Bacteriodes fragilis
Clostridium
71
What are the symptoms of cholecystitis?
Right midepigastric pain at first
Then RUQ pain (referred to the right shoulder)
Vomiting
Fever
Local peritonism, or a GB mass.
72
What is a classic sign of peritonitis?
Rebound tenderness
73
What are the tests for cholecystitis?
**_Ultrasound_**
Thick-walled
shrunken GB (also seen in chronic disease),
pericholecystic fluid, stones, CBD (dilated if \>6mm),
**_MRCP_**
Dye injected
**_HIDA cholescintigraphy_**
Radioactive tracer into vein, should show in gallbladder within 1 hour. BLOCKED.
74
What is Murphy's sign?
Lay 2 fingers over the RUQ; ask patient to breathe in. This causes pain & arrest of inspiration as an inflamed GB impinges on your fingers. It is only +ve if the same test in the LUQ does not cause pain.
75
What is the treatment for cholecystitis?
**_Laparoscopic cholecystectomy_**
**_Pain relieft_**
NSAIDs
**_Antibiotics_**
Cefuroxime IV
76
WHAT IS BILIARY COLIC?
Gallbladder attack or gallstone attack, is when pain occurs due to a gallstone temporarily blocking the bile duct.
77
Compare gallstones for the gallbladder and bile duct locations?
Biliary pain.
Cholecystitis.
Obstructive jaundice.
Cholangitis.
Pancreatitis.
Gallbladder Bile Duct
Biliary pain. Yes Yes
Cholecystitis (inflammation of gall bladder). Yes No
Obstructive jaundice. Maybe Yes
Cholangitis (infection of bile duct). No Yes
Pancreatitis. No Yes
78
What is Leuconychia?
White spots on fingernails.
79
What is spider naevus? Why is it important?
Swollen blood vessels below the skin. Extensive could indicate liver disease.
80
WHAT IS ASCENDING CHOLANGITIS?
Gallstone is stuck in the CBD (choledocholithiasis)
81
What happens in ascending cholangitis?
The flow of bile prevents intestinal bacteria from migrating up the biliary tree and this process is stopped due to the gallstone
82
What are the common bugs for ascending cholangitis?
E. coli
Klebsiella
Enterococcus (group D strep)
83
What are the symptoms for ascending cholangitis?
**_Charcot’s Triad_**
Fever, RUQ pain, Jaundice
**_Reynold’s Pentad_**
Hypotension + confusion
84
What tests can you do for ascending cholangitis?
**_USS abdomen_**
**_MRCP (Magnetic resonance cholangiopancreatography)_**
Locate stone
LFTS
85
What are the treatment options for ascending cholangitis?
**_ERCP (Endoscopic Retrograde Cholangio-Pancreatography)_**
Remove stone
Surgery
Antibiotics for bacterial cholangitis.
86
WHAT IS ASCITES?
Abnormal accumulation of fluid in the abdominal (peritoneal) cavity
87
What are the causes of ascites?
**_Portal hypertension_**
liver cirrhosis
Neoplasia (ovary, uterus, pancreas...)
Congestive heart failure
Advanced kidney failure
88
What is the pathogenesis of ascites?
Increased intrahepatic resistance leads to portal hypertension which leads to ascites. Systemic vasodilation leads to portal hypertension and also secretion of - Renin-angiotensin - Noradrenaline - Vasopressin This then leads to fluid retention. Low serum albumin also contributes to ascites.
89
What are the symptoms of ascties?
Abdo pain
Discomfort
Bloating
90
What are the investigations for ascites?
Physical examination
FBC
Paracentesis to look at fluid
91
What is the managent of ascites?
Treat cause
Limit dietary sodium intake
Diuretics
Therapeutic paracentesis
Surgical shunts
92
WHAT IS ALCOHOLIC LIVER DISEASE?
Liver manifestations of alcohol overconsumption, including
Fatty liver
Alcoholic hepatitis
Fibrosis or cirrhosis
93
What are the three pathways for alcohol after it enters the liver?
Alcohol dehydrogenase
In cytosol
Catalase
Peroxisomes
Cytochrome P450 2E1
94
What do all three pathways lead to the formation of?
Acetaldehyde
95
What does ADH need to convert alcohol to acetaldehyde?
NAD+
96
What does the levels of NAD have to do with liver disease?
As NADH levels increase and NAD+ levels decrease
Higher NADH
More fatty acids
NAD+
less fatty acid oxidation
More fat production
97
What happens at this fatty liver stage?
Patients don't have symptoms or have high levels of neutrophils in the blood
More yellow due to fat deposits
98
What is the buildup of fat in the liver called?
Stenatosis
99
What is also a product of ADH? What do these cause?
**_ROS_**
Hydrogen peroxide
Hydroxyl radical
Superoxide anion
React with different components of hepatocyte
Cause damage to cells
100
What can acetaldehyde do?
Bind to macromolecules and other compounds
When they bind they inihibt the molecule
Acetyaldhyde adducts
Recognised as foreign
Send neutrophils
Neutrophils destroy hepatocytes
101
What happens as the liver cells become inflammed and damaged?
Patient develops alcoholic hepatitis
Mallory bodies appear on histology
Damaged intermediate fillaments
Cytoplasm of hepatocytes
Most commonly seen here
102
What are the symptoms of alcoholic liver disease?
Abdominal (tummy) pain
Loss of appetite
Fatigue
Feeling sick
Diarrhoea
Feeling generally unwell
Jaundice
Oedema
Ascites
Fever
Unusually curved fingertips and nails (clubbed fingers)
Blotchy red palms
Weakness and muscle wasting
Increased sensitivity to alcohol and drugs (because the liver can't process them)
103
What does the progression of ALD look like?
Alcoholic hepatitis coming and going whilst fat and fibrosis rise.
104
What is the diagnosis for alcoholic liver disease?
Hepatomegaly
Neutrohpilic leukocytosis
increased amount in blood
Perivenular fibrosis
ALT increase
AST incease more
ALP increase
GGT increase
Platelet low
Low blood sugar
105
What is the treatment of alcoholic liver disease?
Stop drinking
Corticosteroids to suppress immune system
Diazapam for alcohol withdrawal
Could lead to cirrhosis or liver failure
106
WHAT ARE THE CAUSES OF PORTAL HYPERTENSION?
https://www.youtube.com/watch?v=Cox6Z5pqMBo
Cirrhosis
Fibrosis
Portal vein thrombosis
107
What is the pathology of portal hypertension?
Increased hepatic resistance
Increased splanchnic blood flow
108
What are the consequences of portal hypertension?
Varices (oesophageal, gastric…)
Splenomegaly
109
How are varices formed from cirrhosis and portal hypertension?
Cirrhosis occurs which means less blow flow can get into liver
Pressure builds up in the veins and causes portal hypertension
Anastomosing vien take the path of lowest resistance
Flow towards the heart straight away rather than portal system
Smaller vein dilate causing varices
110
WHAT IS PRIMARY BILIARY CIRRHOSIS?
https://www.youtube.com/watch?v=CQtHOMzLzwU&t=1s
Excess bile and cholesterol in the blood
111
What happens in primary biliary cirrhosis?
Immune damage is directed towards the small bile ducts inside the liver sinusoids.
Granulomas
Eventually, this will result in the destruction of the bile duct branch.
This will cause cholestasis (reduced bile flow).
112
What is the cause of PBC?
Unknown environmental triggers
+ Genetic predisposition (IL12A)
Leading to loss of immune tolerance to self-mitochondrial proteins.
113
What is the epidemology of PBC?
50 Years olds.
Female more than Men.
0.004% incidence
114
What is characteristic of PBC?
Antimitochondrial antibodies
115
How does primary biliary cirrhosis present?
**_Asymptomatic_**
Detected in routine check up
**_Liver failure_**
Ascites
Jaundice
Itching and/or fatigue (pruritus)
**_Cholsesterol_**
Xanthelasma
Hyperpigmentation
Xeropthalmia (dry eyes)
Corneal arcus
Joint pain
116
What are the differential diagnosis of PBC?
Hepatitis
Alcoholic liver disease
Primary sclerosing cholangitis
Non-alcoholic fatty liver disease
117
What are the tests for primary biliary cirrhosis?
**_Blood_**: increased Alk phos, increased gammaGT, and mildly increased AST & ALT.
Late disease: increased bilirubin, decreased albumin, increased prothrombin time.
**_AMA_**
**_Immunoglobulins_**
IgM
TSH & cholesterol increased or same
**_Ultrasound_**
Excludes extrahepatic cholestasis.
118
What is the treatment of primary biliary cirrhosis?
**_Pruritus_**
Colestyramine
**_Fat-soluble vitamin prophylaxis_**
Vitamin A, D, E and K.
**_Ursodeoxycholic acid_** (UDCA)
Decease cholsterol
Liver transplantation
119
WHAT IS PRIMARY SCLEROSIS CHOLANGITIS?
https://www.youtube.com/watch?v=ycDfF0EJssY
Fibrosing of intra-hepatic and extra-hepatic duct
No continous
Onion skin fibrosis
120
What is PSC associated with?
Complication of cholangiocarcinoma
Correlation with ulcerative colitis
121
What happens in PSC?
Autoimmune destruction of cells lining bile duct
122
What autoanitbody is PSC associated with?
pANCA
123
How does PSC present?
Leads to strictures (areas of narrowing) ± gallstones
Presents
Itching
Pain ± rigors
Jaundice
124
What are the tests for PSC?
**_Blood_**: increased Alk phos, increased gammaGT, and mildly increased AST & ALT.
**_Late disease_**
Increased bilirubin, decreased albumin, increased prothrombin time.
**_Immunoglobulins_**
pANCA and IgM
TSH & cholesterol increased or same
**_Ultrasound_**
Excludes extrahepatic cholestasis.
125
What is the treatment for PSC?
Colestyramine for pruritus
Vitamin ADEK supplementation since they are fat soluble
126
WHAT IS HAEMOCHROMATOSIS?
https://www.youtube.com/watch?v=T7ybRVFXRD0
Increased intestinal iron absorption
Iron deposition in joints, liver, heart, pancreas, pituitary, adrenals and skin.
127
What is the cause of haemochromatosis?
Genetic disorder
Autosomal recessive
90% have mutations in HFE gene
Chromosome 6
128
What does the excess iron cause to happen?
Produces ROS which damage the cells they are in
129
What are the symptoms of haemochromatosis?
**_DM_**
‘bronze diabetes’ from iron deposition in pancreas
Dilated cardiomyopathy
Slate-grey skin pigmentation
Tiredness
Arthralgia
Signs of chronic liver disease
130
How can you diagnose haemochromatosis?
**_Transferrin saturation_**
Increased
**_Serum ferritin_**
Increased
**_HFE genotyping_**
**_Liver biopsy_**
131
What is the treatment for haemochromatosis?
Venesect (removing blood)
**_Deferoxamine_**
Binds iron and excretes in urine
Low iron diet
132
WHAT IS NON-ALCOHOLIC FATTY LIVER DISEASE?
Results from fat deposition in the liver not from alcohol
133
What are the risk factors for non-alcoholic liver?
Obesity
Hypertension
Diabetes
Hypertriglyceridemia
Hyperlipidaemia
134
How does non-fatty liver disease cause damage?
Production of ROS
135
What are the symptoms of non-alcoholic liver?
Usually no symptoms;
Fatigue malasie
136
What investigations can you do for non-alcoholic liver?
LFTs Usually ALT; Alk phos, GGT often normal
Fat, sometimes with inflammation, fibrosis (NASH)
137
How can you treat non-alcoholic liver?
Still no effective drug treatments
Wt loss works- the more the better
138
WHAT IS ALPHA-1 ANTITRYPSIN DEFICIENCY?
Genetic condition when alpha-1 antitryspin is absent
139
What is the pathology of alpha-1-antitrypsin deficiency?
Misfolded alpha-1 antitrypsin builds up in hepatocytes
Leading to cirrhosis
Results in inability to export alpha1-antitrypsin from liver
140
What are the symptoms of alpha-1 antitrypsin?
Cirrhosis
Cholestatic jaundice
Inability to make coagulation factors
Buildup of toxins
141
What are the investigations for alpha-antitrypsin deficiency?
Serum alpha1-antitrypsin (1AT) levels lower
**_Liver biopsy_**
Periodic acid Schi (PAS) +ve
Diastaise resistant
**_Liver ultrasound_**
142
What is the treatment for anti-1-antitrypsin deficiency?
Lactulose
Liver transplant
143
WHAT IS WILSON'S DISEASE?
https://www.youtube.com/watch?v=Cr8R\_bnKAtk
Too much copper (Cu) in liver and CNS
144
What type of gene disease is Wilson's disease?
Autosomal recessive
Chromosome 13
Codes for a copper transporting ATPase
145
What is the pathology of Wilson's disease?
In the liver, copper is incorporated into caeruloplasmin.
Copper incorporation into caeruloplasmin in hepatocytes
and its excretion into bile are impaired.
Therefore, copper accumulates in liver, and later in other organs.
ROS made and damage liver
146
What are the manifestations of Wilson's disease?
**_Kayser–Fleischer (KF) rings_**
Copper in iris
**_Neurological signs_**
Due to copper in CNS
**_Liver failure_**
**_Hepatosplenogmegaly_**
147
What are some tests for Wilson's disease?
Urine: Copper high
Serum copper: LOW
Serum caeruloplasmin LOW
Molecular genetic testing can confirm the diagnosis.
Liver biopsy: increase Hepatic copper
MRI: Degeneration of brain
148
What is the management of Wilson's disease?
**_Penicillamine_**
Bind copper, easier to excrete
**_Zinc_**
Decrease copper reabsorption
**_Liver transplantation_**
If severe
149
WHAT IS HELIOCBACTER PYLORI?
Gram negative, curved motile rod, microaerophilic.
150
What is heliocbacter pylori's key biochemical feature?
Urease positivity-used in testing.
151
How is heliocbacter pylori spread?
Oro-fecal or oral-oral.
152
What is the pathogenesis of heliocbacter pylori?
Adapted to living in gastric mucus Colonises over gastric but not intestinal epithelium.
Induces inflammation
Stimulates increased gastrin
153
Why is heliocbacter pylori adapted to live in gastric mucus?
Microaerophilic, motile, urease generates ammonium to buffer acidity.
154
How does heliocbacter pylori stimulate gastrin?
Increased parietal mass but also may modulate gastric acid production.
155
What are the usual symptoms of heliocbacter pylori?
Acquisition usually asymptomatic but may cause nausea and epigastric pain.
Chronic diffuse superficial gastritis
Followed by a period of achlorrydria.
156
How does heliocbacter pylori alter the production of gastrin and what does this result in?
In Antrum: H.pylori reduces somatostatin release by D cells. This leads to loss of inhibition of gastrin release.
G cells now produce increased gastrin levels in the stomach
Increased gastrin levels increases basal acid output
In duodenum: Increased aciditiy leads to gastric metaplasia, H.pylori is then able to colonise duodenum and causes further mucosal damage.
157
What are some disease associations with heliocbacter pylori?
Ulcers.
In the absence of NSAIDS or Zollinger-Ellison syndrome.
Gastric cancer.
Gastric lymphoma.
Oesophageal disease.
Barrett's oesophagus.
Others.
158
What is gastric cancer associated with? Why is this strange? HP?
Reduced gastric acid, strange because in some patients H.pylori reduces gastric acid in some patients.
159
What is the spectrum of gastric acid due to in HP?
Bacterial strain. Genetics. Diet.
160
What investigations can you do for HP?
Serology
Stool antigen
Urea breath test
Endoscopy with urease test
Histology ± culture
161
What is the treatment for HP?
Omeprazole
Amoxicillin
Clarithromycin
162
WHAT IS APPENDICITIS?
https://www.youtube.com/watch?v=r9amif1DQMc
Inflammation of the appendix
163
Where is the appendix?
Connected to the cecum
Also known as veriform appendix (worm shaped)
164
What is the funciton of the appendix?
Uknown
Maybe gut flord hideout
Lymphatics
Vestigial organ
165
What is the epidemology of appendicits?
10% of people get it
Most common surgical emergency
166
What are the causes of appendicits?
**_Obstruction_**
_From_
Feacalith
Undigested seeds
Pinworm infection
Lymphoid follicle growth
Collection of lymphocytes become maximum size in adolesence
Viral infection caues follicle growth
167
What happens when the appendix tube is blocked?
Continues to secrete mucus
This causes it to swell
Presses on the afferent visceral nerve fibres
Causing pain
Flora and bacteria become trapped
168
What bacteria become trapped and what happens as a result?
E.Coli
Bacteriodes fragilis
Immune cells calls WBC
Pus builds up in appendix
169
What happens if the appendix continues to swell?
Blood vessels get compressed
No oxygen
Walls become ischaemic
They die
Bacteria can now invade wall
Can lead to rupture
Caused peritonitis with rebound tenderness
170
What are the symptoms of appendicits?
Right lower quadrant pain
Mcburney's point
Fever
Nausea
Vomiting
171
What are the signs of peritonitis from appendicitis?
Rebound tenderness
Abdominal guarding
172
What is the treatment for appendicitis?
Appendectomy
Antibiotics
Drain abscess
173
WHAT IS PERITONITIS?
Inflammation of peritoneum.
174
What are the causes of peritonitis?
Perforation of GI tract i.e. trauma
175
What are the symptoms of peritonitis?
Pain
Rebound tenderness
Guarding reflex
Fever
Increase in WBC
Shoulder tip pain in sepsis
176
What are the investigations of peritonitis?
Erect CXR - air under diaphragm.
USS/CT
177
How can you treat peritonitis?
IV fluids
antibitoics
Electrolytes
Surgery laparotomy
178
WHAT IS THE DEFINITION OF INTESTINAL OBSTRUCTION?
Blockage to the lumen of gut Intestinal
179
What are some causes of bowel obstruction?
Adhesions
Hernias
Tumour
Crohn’s
Volvulus
Gallstone Ileus
180
How is bowel obstruction classified?
According to site
Extent of luminal obstruction
Mechanical / True ( intraluminal / extraluminal)
Paralytic (Pseudo obstruction)
Simple Closed loop Strangulation Intussusception
181
What is adhesions?
Sticking together abdominal structures to one another, bowel loops or omentum, other solid organs, abdominal wall.
182
What is intesusspition?
Telescoping one hollow structure into its distal hollow structure
183
What are the two types of intesusspition?
idiopathic enteroenteral intussusception (jejunojejunal, jejunoileal, ileoileal), Associated with special medical situations HSP, cystic fibrosis, hematologic dyscrasias
184
What is the mechanism of intesusspition?
an imbalance in the longitudinal forces along the intestinal wall. a mass acting as a lead point or disorganized pattern of peristalsis The invaginating portion - the intussusceptum) the receiving portion - the intussuscipiens.
185
What happens if the mesentery of the intesusspition is lax?
The progression is rapid The intussusceptum - prolapse out the anus. Invagination causes the classic pathophysiologic process of any bowel obstruction.
186
What is atresia?
Absence of opening or failure of development of hollow structure.
187
What is gallstone ileus?
Huge gallstone in gall bladder, inflamed, sticks onto small bowel and erodes through
188
WHAT IS A VOLVULUS?
A twist / rotation of segment of bowel
189
What are the types of volvulus?
Sigmoid (most common)
Cecal
Midgut
190
What is the cause of a sigmoid volvulus?
Pregnancy
Middle aged and eldery constipation
Adhesions
191
What can cause a cecal volvulus and what can cause a midgut volvulus?
Same as sigmoid, mesenteric join loose
Abnormal fetal development for midgut
192
What can happen to a volvulus?
Can twist and stop blood flow to that part
Can release bacteria into body
193
What are the symptoms of a volvulus?
Colicky abdominal pain
Vomiting (earlier with small bowel)
Constipation (earlier with large bowel).
Distension and tinkling bowel sounds.
194
What are the tests for a volvulus?
Abdo X-ray
**_Barium enema_**
Bird's beak
195
What is the treatment for a volvulus?
Sigmoidoscopy
Endoscopy
Surgery
196
WHAT IS A HERNIA?
Protrusion of organ or tissue out of the body cavity in which it normally lies
197
What are some causes of hernias?
Age
Chronic cough
Trauma damage
Failure of abdo wall to close properly in womb
Constipation
Heavy weight lifting
Pregnancy
198
What are the different meanings for these?
Irreducible
Reduction
Incarceration
Obstructed
Strangulated
Irreducible= hernia cannot be pushed back into the right place
Reduction = pushing tissue/organ back into place
Incarceration = contents of hernialsac are stuck inside by adhesions
Obstructed = bowel contents cannot pass through them
Strangulated = if ischaemic occurs
199
What are the different types of hernia?
Hiatal
Inguinal
Femoral
Incisional (after surgery)
Umbilical (\<6m, normally corrects itself)
200
What is the most common hernia and why?
Inguinal hernia
70%
More common in MEN because after testicles descend through canal after birth the canal doesn't always close properly so is weakened
201
What is a direct hernia?
Protrudes DIRECTLY into inguinal canal
Medial to inferior epigastric vessels
202
What is an indirect hernia?
Protrudes through internal inguinal ring
Lateral to inferior epigastric vessels
203
What is a hiatal hernia?
Part of stomach herniates through oesophageal hiatus of diaphragm
204
How does a hiatal hernia occur?
**_Sliding_**
GO junction slides through hiatus and lies above diaphragm
**_Para-oesophageal hernia_**
Gastric fundus rolls up through hiatus alongside oesophagus, GO junction remains below diaphragm
205
What are the symptoms of a sliding hernia?
None unless gastric oesophageal reflux occurs
206
What are the symptoms of a para-oesophageal hernia?
Serious risk of complications (gastric volvulus, bleeding)
207
What are the investigations for a hernia?
Made clinically with history and examination
208
What are the treatments for hernias?
May require surgical repair
Reducing the hernia can prevent strangulation from occurring
209
WHAT IS DIVERTICULOSIS?
https://www.youtube.com/watch?v=TL9\_WKuNfu0
Little pouches at the side of the gut
210
What is diverticular caused by?
High pressure within the lumen pushes part of the intestine out
211
Where can diverticulosis happen?
Any hallow structure in the body
212
What are the types of diverticulosis?
**_True diverticulitis_**
All layers - mucosa to serosa
**_False (pseudo) diverticulitis_**
No muscle layer
213
What is thought to happen when the smooth muscle contracts?
Unequal pressure inside the lumen
The contractions are abnormal and exaggerated
Unclear why
214
What is laplace's law?
Pressure inside a vessel is inversely proportional to the diameter
Decrease in diameter increases pressure
215
Where do most diverticulums occur?
Sigmoid colon
216
What part of the lumen is more affect by diverticulosis?
Where the blood vessels traverse the muscle layer
217
By what part of the gut layer is the divericulum seperated by?
Mucosa
Subject to injury and rupture
Haematochezia
Blood in stools
218
What causes incresed risk of diverticulosis?
Low fiber foods leads to constipation
Fatty foods and red meat
Marfan's syndrome
Ehlers-danlos syndrome
219
WHAT IS DIVERTICULAR DISEAESE?
Diverticula + complications e.g. infection, hemorrhage, infection
220
What is the symptoms of diverticular disease
Usually no symptoms
Sometimes stomach pain and bleeding
221
What can happen if a outpouching ruptures?
Can form a fistula
Connection between it and another organ
Most commonly the bladder
222
What is the tests for diverticular disease?
Flexible sigmoidoscopy
Barium enema
223
What are the treatment options for diverticular disease?
Diet more fibre
Smooth muscle relaxants
224
WHAT IS DIVERTICULITIS?
Inflammation of diverticula
225
How can a diverticulosis become a diverticulitis?
Inflammation
Through high pressures erroding the wall
OR
Lodged fecalith
226
What are the symptoms of diverticulitis?
LIF pain
Fever
Abdoguarding
Tachycardia (similar to appendicitis but on the left)
227
What are the tests for diverticulitis?
USS
Bloods (ESR, CRP)
Sigmoidoscopy
228
What is the treatment of diverticulitis?
Antibiotics
High fiber
Surgical removal
229
WHAT DOES GRAPHS OF COLORECTAL CANCER SHOW?
Environmental causes.
230
What do older people have?
Polyps in colon.
231
What causes a predisposition to cancer?
polyps.
232
What can happen with cancer in the colon?
Go to a dysplastic epithelium but not to cancer.
233
What is the normal progression of the colon into cancer?
Normal epithelium. Adenoma. Colerectal adenocarcinoma.
234
What is a genetic condition that can predispose to colorectal cancer?
familial adenomatous polyposis
235
How does familial adenomatous polyposis cause cancer?
APC bound GSK suppose to break down beta catenin, APC ascent in FAP, beta catenin builds up and causes epithelial proliferation.
236
What is hereditary nonpolyposis colorectal cancer HNPCC?
Two hits of DNA repair protein. No DNA repair.
237
What are the reasons for identifying HNPCC cancers?
risk of further cancers in index patient and relatives possible implications for therapy tolerance of 5-FU etc. do not recognise DNA damage apoptosis not activated.
238
Where is the most common site for cancer?
Rectum.
239
What is colorectal cancer called?
Adenocarcinoma.
240
What is important is cancers?
Can do staging, using whether it has spread to lymph nodes, how big tumour is.
241
What is the resection margin?
Area around a tumour that has been cut out which is not cancerous.
242
What are the different resection coding?
R0 - tumour completely excised locally R1 - microscopic involvement of margin by tumour R2 - macroscopic involvement of margin by tumour.
243
Why should you stage a tumour?
To give prognosis and see life expectancy.
244
How does staging of tumour work?
As it progresses it goes higher.
245
What are the Duke stage prognosis?
A 95% 5 year survival B 75% 5 year survival C 35% 5 year survival D 25% 5 year survival.
246
What are Dukes classification?
Duke A in gut. Duke B just outside gut. Duke C lymph node. Duke D high tie lymph node.
247
How do you treat normal epithelium going to adenomas?
prevention. Low dose aspirin.
248
How do you treat an adenoma?
endoscopic resection
249
How do you treat a colorectal adenocarcinoma?
surgical resection.
250
How do you treat a metastatic colorectal adenocarcinoma?
chemotherapy and palliative care
251
What does Duke's classification not take into account?
Peritoneum.
252
WHAT ARE THE CAUSES OF DIARRHOEAL DISEASES?
Infective causes and non-infective.
253
What are some non-infective causes of diarrhoea?
Neoplasm. Hormonal. Inflammatory. Radiation. Irritable bowel. Chemical. Anatomical.
254
What are the infective causes of diarrhoea?
Non-bloody and bloody (dysentery)
255
What are some different types of transmission?
Direct Direct route. STIs Faeco-Oral route. Viral GE Indirect Vector-bourne Malaria Vehicle-bourne Viral GE Airborne Respiratory route TB
256
27 year old student just returned from backpacking holiday around South Asia. Presents with frequent bouts of diarrhoea, flatulence, nausea and abdominal discomfort. What is this a case of?
Vibrio cholerae
257
2 year old child presents with loose stools for 2 days. Miserable. Loss of appetite but drinking ok. No fever. Attends nursery and playgroup. Recently been to a petting zoo. What is this a case of?
Escherichia coli
258
87 year old resident of a care home presents with confusion, altered consciousness, dehydration and a history of diarrhoea. What is this a case of?
Norovirus
259
What is the norovirus?
Major cause of “Winter Vomiting” Mainly occurs in the winter Mainly causes vomiting May cause diarrhoea, nausea, cramps headache, fever, chills, myalgia Lasts 1-3 days Immunity is short lived
260
36 year old man presents with bouts of low volume bloody stools. He works in a take-away. What is the a case of?
Shigella.
261
84 year old patient at the Northern General Hospital presents with diarrhoea. She is recovering from a surgical operation a few days ago. What is the a case of?
Clostridium difficile.
262
What is clostridium difficile associated with?
Associated with antibiotic use Especially broad spectrum antibiotics In hospitalized patients cause Antiobitic-associated diarrhoea Antibiotic-associated colitis Pseudomembranous colitis Mortality high Especially as patients tend to be elderly and ill
263
What is the epidemiology of clostridium difficile?
Asymptomatic carriage occurs in 2-3% of healthy adults, 2/3 of babies ~36% of hospital patients Spread by faeco-oral route directly or through spores in the environment. Asymptomatic carriers without diarrhoea unlikely to spread it. 80% of symptomatic cases in persons \> 65 years Causes 20% of antibiotic-associated diarrhoea
264
How can you prevent clostridium difficile?
Clostridium difficile produces spores highly resistant to chemicals (spores) Alcohol hand rubs will not destroy the spores. Hand washing using soap and water will remove the microorganisms (including spores) from the hands.
265
What is SIGHT?
S uspect C diff as a cause of diarrhoea I solate the case G loves and aprons must be worn H and washing with soap and water T est stool for toxin.
266
How do you manage a clostridium difficile patient?
Control antibiotic usage Esp. Ampicillin, amoxicillin & cephalosporins Standard infection control procedures Surveillance & case finding Any patient with diarrhoea Isolate Enteric precautions Test stool samples Environmental cleaning Treat cases with metronidazole or vancomycin
267
What do you test for clostridium difficile?
Test stool samples for the toxin Can also culture it (in order to identify which strain it is) Tissue samples (histology) obtained at sigmoidoscopy Don’t need to screen or treat asymptomatic carriers
268
WHAT IS A PEPTIC ULCER?
https://www.youtube.com/watch?v=26Rdx2EiBaA
Having one or more sores in the stomach, gastric ulcers or duodenum, duodenal ulcers
269
What does the normal gut look like?
Mucosa which contains
**_Epithelial cells_**
Absorbs and secretes digestive enzymes
**_Lamina propria_**
Blood and lymph vessels
**_Muscularis mucosa_**
Smooth muscle contracts/breaks
270
What are the different regions of the stomach?
Cardia
Fundus
Body
Pylroic antrum
271
What cells does the cardia have?
Fovelar cells
Water and glycoproteins
272
What cells do the fundus and body have?
Parietal cells
Secrete HCL
Chief cells
Secrete pepsinogen
273
What cells does the antrum have?
G cells
Secrete gastrin in repsonse to food entering
Also found in duodenum and pancreas
274
What does gastrin do?
Triggers parietal cells to release HCL
Also stimulates growth of glands in epithelial layer
275
What are brunner glands?
Found in duodenum and secrete mucus rich in bicarbonate into lumen
276
What protects the stomach and duodenum?
Mucus and secretion of bicarboante ions to neutralise acid
277
What is also brought in the blood to the stomach and duodenum?
Bicarbonate ions
278
What gets secreted by epithelial cells in the stomach and duodenum, what do they do?
Prostaglandins
Stimulate mucus and bicarbonate secretion
Also dilation of nearby blood vessels
More blood to area
New epithelial cell growth
Inhibits acid secretion
279
What are the causes of peptic ulcers?
H.pylori infection
NSAIDs
Zollinger-ellison syndrome
280
Where is H.pylori most common? What type is it?
Low income settings
Gram negative bacteria
281
Where do helicobacter live?
In the mucus layer in the stomach.
282
What does helicobacter do?
Release adhesins which allow them to stick to fovelar cells
Secrete proteases which damage mucosal cells
Starts in antrum and spreads
Errodes deeper and deeper causing ulcers
283
What can happen to the epithelial lining in helicobacter pylori?
Change from stomach epithelium to intestinal epithelium. Intestinal metaplasia.
284
What do NSAIDs do?
Inhibit COX-2
Inhibit synthesis of prostaglandins
Gastric mucosa suseptable to damage
285
How can you avoid COX-2 inhibition by aspirin?
Produce aspirin with enteric coat on it, therefore won't dissolve in stomach but lower down in gut.
286
What is zollinger-ellison syndrome?
Tumour called a gastrinoma
Neuroendocrine tumour
gastrin produced in excess
More HCL
Overwelms duodenum
Causing ulcers
287
What do ulcers normally look like?
Smooth punched out holes
Like a dishwasher
288
Where do ulcers normally appear?
Gastric in lesser curvature
Duodenum in first part
Brunner gland hypertrophy
289
What can happen in ulceration to an artery?
Can eat into the artery and start haemorrhaging.
Stomach - will come straight up Intestine - black stools.
Coud lead to shock
Lesser curvature - left gastric artery
Posterior wall - gastroduodenal artery
290
What can happen in ulceration to the muscle?
Ulceration through the muscle
Which allows free flow of contents in the peritoneum
Causing peritonitis.
Anterior part of duodenum
Trap air
Causing irritation of phrenic
Referred pain to shoulder
291
What can ulceration lead to on the posterior side?
Erode through into the pancreas to give pancreatitis.
292
What happens when the blood flow slows to the gut?
Cells break down as the buffer is not produced as much, the acid the attacks the cells and an ulcer forms.
293
What can happen from a breach in the cells in the mucosa?
Acid attack adjacent cells.
294
What are the symptoms of peptic ulcers?
Epigastric pain - aching in abdomen
Bloating
Belching
Vomiting
295
When do symptoms improve for gastric and duodenal ulcers?
Gastric when not eating
Duodenal when eating
296
What is the diagnosis of peptic ulcers?
Endoscopy
**_C13 Urea breath test_**
H pylori
**_Biopsy_**
Check for malignancy
H.pylori
297
How could you treat peptic ulcers?
H.pylori
Antibiotics (Omeprazole, Metronidazole, Clarithromycin)
Acid lower medications
**_Proton pump inhibitors_**
Lansoprazole
**_H2 blocker_**
Rantidine
Surgery
298
What makes gastric ulcers worse?
NSAIDs
Smoking
Caffiene
Alcohol
299
WHAT IS GASTRITIS?
Irritation of stomach lining without an ulcer
300
What are the causes of gastritis?
Excessive alcohol
NSAIDs
Spicy foods
Stress
301
What are the symptoms of gastritis?
Epigastric pain
Loose stools
Vomiting
Haematemesis.
302
How can you diagnose gastritis
Endoscopy + biopsy
303
What is the differential diagnosis of gastritis?
Ulcerative collits
Chron's
IBS
304
What is the treatment for gastritis?
Ranitidine or PPI; eradicate H. pylori as needed.
Troxipide PO improves gastric mucus.
Endoscopic cautery may be needed.
305
What is the treatment for H.pylori?
Lansoprazole, amoxicillin, and clarithromycin (LAC)
306
WHAT IS THE STRUCTURE OF THE SMALL INTESTINE?
Villi and crypts.
Crypts provide new cells for the villi.
307
What is located in the tips of the villi?
Lymphocytes.
308
What are the different types of malabsorption?
Insufficient intake.
Defective intraluminal digestion.
Insufficient absorptive area.
Lack of digestive enzyme.
Defective epithelial transport.
Lymphatic obstruction.
309
What can defective intraluminal digestion be caused by?
**_Pancreatic insufficiency_**
Pancreatitis
Cystic fibrosis
**_Defective bile secretion (lack of fat solubilisation)_**
Biliary obstruction
Ileal resection – decreased bile salt uptake
**_Bacterial overgrowth_**
310
What is Giardia lamblia?
Giardia lamblia, also known as Giardia intestinalis, is a flagellated parasite that colonizes and reproduces in the small intestine, causing giardiasis.
The parasite attaches to the epithelium by a ventral adhesive disc, and reproduces via binary fission.
311
What is involved with small intestine resection or bypass?
procedure for morbid obesity Crohn’s disease infarcted small bowel
312
What is involved with lack of digestive enzymes?
disaccharidase deficiency (lactose intolerance) bacterial overgrowth – brush border damage.
313
What is involved with defective epithelial transport?
abetalipoproteinaemia primary bile acid malabsorption – mutations in bile acid transporter protein
314
What is involved with lymphatic obstruction?
lymphoma tuberculosis
315
What are the chronic idiopathic inflammatory bowel disease conditions? What are the other inflammatory conditions?
Crohn's disease. Ulcerative colitis. Diverticulits. Ischameic colitis. Infective colitis - bacterial and protozoal.
316
WHAT IS CROHN'S DISEASE?
Massive inflammation and associated ulcers.
Transmural granulomatous inflammation
317
What is the cause of crohn's?
Genetic
Family history likely to get it
Frameshift mutation in NOD2 gene
CARD15
Insertion
318
Where is Crohn's disease most common?
Terminal Ilieum.
319
Where can ulceration/granulomatous inflammation be found in Crohn's?
Whole length of the GI tract
PATCHY
Throughout the mucosa, submucosa, muscular propriety and fat of the gut.
320
What type of disease is Crohn's disease?
Immune related disease
321
What are the bacteria thought to be responsible for Crohn's?
Mycobacterium paratuberculosis
Pseudomonas
Listeria
322
What happens in crohn's?
Immune response occurs in reponse to pathogen but is wide and damages cell in GI tract
Defect in epithelial wall which lets bacteria in
323
What happens when the bacteria comes in?
GI epithelial cell present bacteria on surface
T helper cells come along
They release inflammatory cytokines
Infereron gamma
Tumour necrosis factor alpha
These attract macrophages
324
What do the macrophages release?
ROS
Proteases
Platelet-activating factor
325
What is thought to happen in crohn's disease?
The process of antigen presenting and macrophage attraction is dysfunctional
Leading to unregulated inflammation
Lots of proteases
Lots of ROS
Lots of platelet-activating factor
Destroying tissues
326
What does all the immune cells in the GI wall cause?
Granulomas
327
What is formed in both ulcerative colitis and crohn's?
Ulcers
328
Where do crohn's ulcers extend?
All the way through muscle layer
Ulcerative colitis does not
329
What are the symptoms of crohn's?
Pain in assocaited areas
RLQ
Diarrhoea and blood in stool
If affecting large bowel
Malabsorption
If affect small bowel
330
What are the test for crohn's disease?
Acutely can sound like Appendicitis.
```
**_Barium Swallow_**
COBBLESTONE APPEARANCE (may also have stricture formation and bowel shortening)
```
**_CT_**
Shows areas of wall thickening
**_Colonoscopy (and biopsy)_**
DIAGNOSITIC
331
What does the histology look like for crohn's?
Skip Lesions
Transmural inflammation
Increase in Goblet cells
Non-Caseating Granulomas
332
What are the treatment option for crohn's?
NSAIDs
Antibiotics
Reduce bacteria levels in intestine
**_Immunosuppresants_**
Corticosteroids
Surgical removal doesn't cure disease
333
What are some Crohn's disease complications?
Malabsorption
-disease extent -surgical resections
Obstruction
-acute swelling -chronic fibrosis
Perforation
-acute abdomen
Fistula formation
Osteoporosis
Neoplasia
-colorectal cancer
334
What different surgical resections are there?
Ileocolonic anastomosis
Jejunocolonic anastomosis
End-jejunostomy
335
WHAT IS ULCERATIVE COLITIS?
Inflammation in the large intestine forming ulcers including colon and rectum
336
What is the cause of ulcerative collitis?
Autoimmune
Stress and diet make it worse
337
What are found in large amounts lining the colon?
Cytotoxic T cells
These destroy cells in the large intestine
338
What do a large amount of people with ulcerative collitis have?
p-ANCAs
Thought to be due to bacteria mimicary
Increase in Sulfide gut bacteria
339
What is the epidemology of ulcerative collits?
Family history positive
Women
30s
Caucasions and eastern europeans
340
Where does ulcerative collitis start and what does it look like inside the lumen?
Rectum
Makes way round with no breaks
Circumfrential and continuous
341
What can ulcerative colitis involve?
Inflammatory disorder of the colonic mucosa.
Does not involve the muscle
Forming ulcers
342
What happens in flares and remission?
New ulcers forms
Ulcers heal
343
How do you distinguish ulcerative colitis from Crohn's disease?
Ulcerative colitis only involves mucosa whilst Crohn's involves many layers of the gut.
344
What is the pathology of ulcerative colitis?
Hyperaemic/haemorhagic granular colonic mucosa and maybe pseudo polyps formed by inflammation.
345
What are the symptoms of ulcerative colitis?
Pain in LLQ
Episodic or chronic diarrhoea
Cramps abdominal discomfort
Bowel frequency relates to severity
Urgency/tenesmus.
Fever, malaise, anorexia, weight.
346
What are some complications of ulcerative colitis in the skin?
Erythema nodosum
pyoderma gangrenosum
347
What are some complications of ulcerative colitis in the colon?
Blood loss toxic dilatation
Colorectal cancer.
348
What are some complications of ulcerative colitis in the liver?
fatty change chronic pericholangitis sclerosing cholangitis
349
What are some complications of ulcerative colitis in the joints?
ankylosing spondylitis arthritis
350
What are some complications of ulcerative colitis in the eyes?
iritis uveitis episcleritis
351
What would show on histology for UC?
Continuous superficial inflammation
Crypt Abscesses
Goblet cell depletion
Ulcers
Only rectum affected (not proximal to ileocaecalvalve)
352
What investigations can be done for ulcerative colitis?
Bloods
**_BARIUM SWALLOW_**
Loss of haustrations and drain pipe colon
**_XR_**
No faecal shadows; mucosal thickening/islands, colonic dilatation
**_Stools_**
Exclude bacteria
**_Colonoscopy_**
Look for inflammatory infiltrate; goblet cell depletion; glandular distortion; mucosal ulcers; crypt abscesses.
Sigmoidoscopy and biopsy - \*\*\*DIAGNOSTIC
353
What are the principles of management for ulcerative colitis?
**_5-Aminosalicylic Acid_**
**_Inducing remission_**
Sulfasalazine
Mesalamine
Steroids - Prednislone.
Cyclosporine
**_Surgery_**
Colectomy
354
WHAT IS THE OESOPHAGUS LINED BY?
Squamous epithelium.
355
What is the stomach lined by?
Glandular epithelium.
356
What happens in barrett's oesophagus?
Change from squamous epithelium to glandular. Columnar lined lower oesophagus.
357
What is metaplasia?
Change in differentiation of a cell from one fully- differentiated type to a different fully-differentiated type.
358
What does reflux of acid into the oesophagus cause?
Destruction of the squamous cells and ulceration.
359
What can cause acid reflux?
Obesity - increased intra-abdominal pressure.
360
What can develop from this acid reflux and changing of cells?
Adenocarcinoma.
361
What is the progression of cell type in Barrett's oesophagus?
Normal Metaplasia Dysplasia Neoplasia. As a result of on going acid reflux.
362
What are the different types of oesophageal cancers for different parts of the world and why?
China have squamous cancer by smoking and drinking. Europe has adenocarcinoma by acid reflux and obesity.
363
What happens when a cancer grows in the oesophagus, at what point can you not remove it?
Could metastasise into the wall of the oesophagus, could move to far so that it comes into close contact with the superior vena cava and other major vessels.
364
What is a risk factor for gastric cancer?
Eating certain foods such as pickled and smoked foods,. Asia.
365
What can helicobacter pylori put you at a predisposition to? Why is this?
Gastric cancer. Due to intestinal metaplasia.
366
What is limits plastica?
Cancer cells everywhere producing a plastic like feel.
367
What is early gastric cancer?
Anything that doesn't go into the muscular wall.
368
What is late gastric cancer?
Into the muscular wall and lymph nodes.
369
WHAT IS IBS?
Recurrent abdominal pain and abnormal bowel motility
370
What are the symptoms of IBS?
Constripation and/or diarrhoea
Symptoms improve after voiding
Does not involve inflammation
371
What is the cause of IBS?
Uknown
372
What happens with visceral hypersensitivity in IBS?
Sensory nerve ending s
Abnormaly stong response to stimuli
When eating
Recurrent abdo pain
373
How does increased bowel motitlity work with IBS?
Short-chain carbohydrates
Fructose and lactose act as solutes
Draw water into lumen
Stretch lumen causing pain
Smooth muscle spasm and diarrhoea
Gut flora metabolise short chain and produce gas
374
What is the epidemology of IBS?
**_North america_**
Middle aged women
Other parts
Both sexes equally
375
What are some risk factors for IBS?
**_Gastroenteritis_**
Norovirus
Rotovirus
Stress
376
What is the treatment of IBS?
Diet modification
Avoid certain food, apples, beans and caulifflour
**_Constipation_**
Soluble fibre
Stool softeners
Laxatives
**_Spasms_**
Antimuscarinic
**_Manage stress_**
**_LOW FODMAP_**
Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols
377
WHAT IS COELIACS DISEASE?
https://www.youtube.com/watch?v=nXzBApAx5lY
Autoimmune response which attacks the small intestine
378
What is in wheat?
Individual wheat kernals
Inside each kernal is endosperm
For seeds embryos
This endosperm contains protein and starch
The protein is gluten
379
What is the main culprit of coeliacs?
Gliadin found in gluten
380
What happens when somebody eats food contain gluten?
Broken down in stomach in gliadin and other stuff
381
What happens to gliadin after the stomach?
Gliadin resists break down
Gets to small intestine
Binds to secretory IgA
IgA normally protects enterocytes
Should normally be destroyed but isn't
It then binds to transferrin receptor
Moves across cell into lamina propria
382
What happens when the gliadin-IgA complex gets into the lamina propria?
Tissue transglutaminase cuts off amide group from protein
Deaminated gliadin eaten by macrophages
Displayed on MHC2
383
What codes for MCHs?
HLA genes
384
What genes do coeliac's normally have?
HLA DQ2
HLA DQ8
385
What happens when the macrophage presents gliadin to other immune cells?
**_T helper cell (CD4+)_**
Recognise gliadin
Release inflammatory cytokines
IFgamma
TNF
These destory epithelial cells in small intestine
**_T cells also activates B cells to secrete antibodies_**
Anti-gladin
Anti-tTG
Anti-endomyseal
**_T cells also activate cytotoxic T cells_**
These directly destory epithelial cells
386
Why are antibodies produce to tTG moleucles in endomysium? Why are they helpful?
No symtpoms
Structual transglutaminase in lamina propria
Useful for diagnosis
387
What screening tests can be used?
Anti-tTG and anti-endomyseal useful in severe cases
388
What happens if a patient is IgA deficient?
Need to have an IgG screening test
389
Which part of the intestine is mainly affected by coeliacs?
Duodenum
390
What are the signs seen in the intestinal wall for coeliac's?
Villi destoryed and flattened out
Villus atrophy
Crypts get longer
Crypt hyperplasia
Lymphocyte infiltration
391
How does coeliac's disease present?
**_Classical_**
Diarrhoea
Steatorrhoea
Weight loss
Failure to thrive
**_Non-classical_**
Irritable bowel type symptoms
Iron Deficiency
Anaemia
Osteoporosis
Chronic Fatigue
Dermatitis Herpitiformis
Ataxia
Peripheral neuropathy
Hyposplenism
Ammenorhoea Infertility
392
What is Dermatitis Herpetiformis?
Rash common with coeliac disease patients.
Bumpy skin rash which pops up from IgA antibodies
Transglutaminase in dermal papillae
Neutrophils come by and start reaction
393
What commonly happens with the presentation of coeliac's disease?
More non-common presentations then common.
394
How do you test for coeliac's disease?
**_Serology_**
Tissue transglutaminase (tTG)
Anti-endomysial antibody (EMA)
Immunoglobulins.
Endoscopy + Duodenal biopsies.
**_Histology_**
Villous atrophy.
395
What do patients need to do when undergoing testing for coeliac's?
testing is accurate only if they follow a gluten-containing diet when following a gluten- containing diet they should eat some gluten in more than one meal every day for at least 6 weeks before testing they should not start a gluten- free diet until diagnosis is confirmed by intestinal biopsy
396
What are the different stages of coeliac's disease? 0. 1 2 3a 3b 3c
0. Normal 1. Raised Intra epithelial Lymphocytes (IEL) \>30/100 enterocytes 2. Raised IEL + Crypt Hyperplasia 3a. Partial Villous Atrophy (PVA) 3b. Subtotal villous atrophy (SVA) 3c .Total villous atrophy TVA)
397
Where will a duodenal biopsy be taken from for coeliac's?
1 x Duodenal bulb (new) 4 x D2 (traditional)
398
How many duodenal biopsy's should be taken to make sure the most severe lesion is identified?
5.
399
How do you manage coeliac's disease?
Gluten free diet – strict and lifelong
Dietician review
DEXA scan- osteoporotic risk
Coeliac UK info.
Prescription entitlement Inform 10% risk in 1st degree relatives.
400
What happens if coeliac's disease is left untreated?
Persistent symptoms
Osteoporosis
Subfertility
Cancer risk
Quality of life.
401
What is the percentage of osteoporosis in coeliac's disease?
40-60% of untreated adult CD Fracture risk Clinical, subclinical and silent affected Adherence improves BMD
402
What is the associated cancer risk with coeliac's disease?
2 fold increase in cancer and mortality compared with controls Small bowel lymphoma Oesophageal and ENT malignancies Lung and breast cancer LESS likely
403
WHAT IS TROPICAL SPRUE?
https://www.youtube.com/watch?v=In1uajyiSxE
GI disease that results in malabsorption of nutrients in water
404
What is the cause of tropical sprue?
Uknown
405
What happens to the villi in tropical sprue?
Villi become flattened
406
What is thought to be the pathology of tropical sprue?
Bacteria, virus or protazoa initially damage gut wall
Cause inflammation
Enteroglucagon released by enterocytes
Decreases intentinal motility
407
What happens with this decreased intentinal motility?
Food lingers longer in intestine
More food means more resources
Change in bacteria flora
Bacteria overgrowth
One type of bacteria dominate flora
408
What are the bacteria in tropical sprue?
Klebsiella
E.Coli
Enterobacter
409
What does the bacteria in tropical sprue do?
Release toxic byproducts in fermention
Which causes more inflammation
Villi atrophy
410
What does villi atrophy lead to?
Less surface area and enzymes for digestion
More food for bacteria
Depletion of B12 and folate
411
What is folate needed for?
Needed to maintain integrity of mucosal wall
412
What are the symptoms of tropical sprue?
Has flare ups
Diarrhoea
Abdominal pain
Fatigue
Weight loss
Dehydration
413
What is a complication of tropcial sprue?
Megaloblastic anaemia
Large immature RBCs
414
What is the diagnosis of tropical sprue?
Lived in tropics and have long standing GI symptoms
**_Fat malabsorption_**
72 hour stools test on prescribed diet
**_Carbohydrate malabsorption_**
D-xylose absorption test
**_Imaging techniques_**
Endoscopy
Villi atropy
Barium swallow
intestinal wall thickening
**_Tissue biopsy of jejenum_**
415
What is the treatment for tropical sprue?
**_Antibiotics_**
Tetracycline
**_Nutrition_**
Folate
B12
416
WHAT IS MALLORY-WEISS TEAR?
https://www.youtube.com/watch?v=YEaP\_P5HrLQ
A longtitudinal tear in the mucosa lining at the gastroesophageal opening
417
What is the cause of mallory-weiss?
Anyhting that causes a suddden rise in intragastric pressure
Normaly prolonged vomiting
Persistant retching
Intentse coughing
Alcholic binge drinking
Beluimic
Gastritis
418
What are the symptoms of Mallory-Weiss?
Upper GI pain
Severe vomiting
Vomiting blood (Hematemisis)
Bloody or black stools (Melena)
419
How can you diagnose Mallory-weiss?
**_Pateint history and presenting complaint_**
Binge drinking?
Bulimic?
**_Upper GI endoscopy_**
See tear in mucosa
**_FBC_**
Low RBC
420
What are the treatment options for Mallory-weiss?
**_Most of the time it heals itself_**
IV fluid
Oesophagus balloon tamponade
Oesophageal clips
Proton pump inhibitors
Sclerotherapy (medications close off vessel)
Coagulation therapy
421
WHAT ARE OESOPHAGO-GASTRIC VARICES?
https://www.youtube.com/watch?v=06nBQxYro8s&t=37s
The dilated veins that are in the distal oesophagus
422
What causes varices?
Increase in portal venous system
423
What happens when these veins rupture?
Cause mass amount of bleeding
424
What diseases cause varices?
Liver cirhosis
Alcoholics
425
How does liver cirrhosis cause varices?
progressive liver fibrosis + regenerative nodules produce contractile elements in the liver’s vascular bed
Portal hypertension
Causes veins in oesophagus to become engorged and serpentine
426
What happens when the pressure in the veins becomes more than 12?
The varices can rupture
427
What are the symptoms of varices?
History
Alcoholic
Upper GI bleeding
More than Mallory Weiss
428
How do you diagnose varices?
Endoscopy
FBC
PT
PTT
LFT
429
What is the treatment for varices?
**_Octreotide IV_**
Decreases blood flow
Inhibits vasodilation
**_Non-selective beta blockade_**
Propanalol
**_Endoscopic banding_**
Put rubber band around enlarged veins
**_TIPS_**
Transjugular, intrahepatic portosystemic shunting
Bypass between portal and hepatic venous circulations
430
WHAT IS ACHALASIA?
https://www.youtube.com/watch?v=Ck5Xhre-UZU&t=1s
Lower esopahgeal sphincter does not relax
Esophagus dilates
431
What is the cause of achalasia?
Loss of LOS nerve innervation
Loss of ganglion cells
432
What are the features of achalasia?
Impaired of peristalsis
Lack of relaxation of LOS
Increased pressure
433
What are the symptoms of achalasia?
Dysphagia - difficulty swallowing
Patinet will regurgitate food at night
Cough
Pulmonary aspiration
Weight loss
434
What is the diagnosis of achalasia?
**_Oesophageal monometry_** - catheter down esophagus
Assess peristalsis
100% failed peristalsis
Function of LOS
Incomplete relaxation
Increased pressure
**_Barium swallow_**
Fluid stuck in esophagus
Bird's beak
435
What is the treatment for achalasia?
Try to open LOS
Decrease pressure at LOS
**_Surgical myotomy_**
Cut muscles of LOS
**_Balloon dilation_**
Then proton pump inhibitors
436
WHAT IS SCLERODERMA?
Collagen deposition in skin and other organs
437
What is the epidemology of scleroderma?
30-50 years
Women more than men
438
What is the cause of scleroderma?
Uknown agent causes disease in suseptable host
439
What is thought to be the cause of scleroderma?
Viruses
Chemicals
HLA genes
440
What are the cells affected?
Fibroblasts
Excess of collagen in skin
Endothelium
Contriction of arteries
Immune cells
Dysregulated production of cytokines and antibodies
441
What can the antibodies do?
Complex with self antigens forming immune complexes
Immune complexes and cytokines
Damage blood cells
Produce more collagen
442
What antibody is involved with scleroderma?
Limited: Anticentromere
Diffuse: Antitopoisomerase-1
443
What are the symptoms of scleroderma?
**_CREST_**
Raynaud's phenomenom
Skin develops hard texture
Cannot be wrinkled
Face is expressionless
Claw like fingers
444
How is scleroderma involved with GI?
Esophagus loses elasticity and becomes firm
Difficulty in swallowing
445
What is the diagnosis of sclermoderma?
**_Radiography_**
Diffuse widening of peridontal ligament space
**_Microscopy_**
Excess collagen in stroma of organ involved
446
What is the cure of scleroderma?
No cure
**_Immunosuppresants_**
Cyclophosphamide
