Liver & Co. Flashcards
1
Q
what are the fat soluble vitamins?
A
A, D, E, K
2
Q
name 3 functions of phase I reactions in liver detoxification?
A
- inactivate drugs
- further activate drugs
- activate drug from pro-drug
- make a drug into a reactive intermediate
3
Q
What is the purpose of phase 1 reactions?
A
addition / exposure of a reactive site that can be used for conjugation reactions in phase 2 (functionalisation)
4
Q
what are phase 1 reactions catalysed by?
A
cytochrome P450 enzymes
5
Q
what is the purpose of phase II reactions?
A
to increase the hydrophilicity of the drug for renal excretion
6
Q
what is the general mechanism for phase II reactions?
A
They are conjugation reactions.
Attachment of substituent groups, reaction catalysed by transferases.
7
Q
what type of reactions take place during phase I reactions?
A
oxidation, reduction and hydrolysis
8
Q
what is the function of albumin?
A
binding and transport of large hydrophobic compounds e.g bilirubin
9
Q
what clotting factors does the liver not produce?
A
calcium and von Willebrand factor
10
Q
what clotting factors need Vitamin K for their synthesis?
A
10, 9, 7, 2 (1972)
11
Q
what is the role of complement factors?
A
plasma protein which opsonizes
12
Q
what is a portal tract
A
contains branches of portal veins, arteries and bile duct
13
Q
what are sinusoids?
A
highly specialised blood vessels that permits the exchange of material within blood
14
Q
what are the stem cells in the liver known as
A
hepatic stellate cells
15
Q
what are Kupffer cells
A
resident macrophage in the liver
16
Q
what is the space of Disse
A
space between the vascular endothelial cells of the sinusoid and the hepatocyte (perisinusoidal space)
17
Q
what is the path from synthesis to storage of bile?
A
- hepatocytes synthesise bile
- bile drains into the canaliculi which lie inbetween individual hepatocytes
- then into bile ductules
- then to bile ducts
- if bile does not pass straight into the duodenum then it is stored in the gallbladder.
18
Q
what attaches the liver to the anterior abdominal wall
A
falciform ligament
19
Q
what is the bare area of the liver
A
large area on diaphragmatic surface of liver that is directly attached to the diaphragm
20
Q
what are the lobes of the liver
A
right lobe
left lobe
caudate lobe
quadrate lobe
21
Q
what is the anatomy of the biliary tree
A
- Right and left hepatic ducts join to form the common hepatic duct
- The cystic duct is comes from the gallbladder and joins the common hepatic duct to form the common bile duct
- Pancreatic duct joins onto the common bile duct to form ampulla of Vater
- Bile duct enters the descending part of the duodenum at the major duodenal papilla (where the ampulla of Vater is located )
22
Q
what are the contents of bile?
A
- bicarbonate ions
- cholesterol
- lecithin
- bile pigments
- bile salts
23
Q
what is bile used for?
A
the emulsification and absorption of fats in the the duodenum
24
Q
what is the predominant bile pigment
A
bilirubin - a yellow substance resulting from heme breakdown
25
Outline bilirubin metabolism
1. RBC are produced in bone marrow by erythropoesis
2. when RBC become damaged/old macrophages in the spleen/bone marrow engulf and degrade them
3. Hb molecule released
4. Hb breaks down into heme and globin
5. Heme is metabolised into Fe2+ and BILIVERDIN (green pigment)
6. Biliverdin is rapidly reduced into UNCONJUGATED BILIRUBIN (UCB)
7. UCB is yellow, toxic and lipid soluble
8. UCB binds to albumin and is transported to the liver
9. UCB enters the liver and undergoes a conjugation reaction with glucoronic acid to become CONJUGATED BILIRUBIN which is water soluble
10. conjugated bilirubin can be excreted by the liver in bile through the common bile duct
11. Conjugated bilirubin travels through the SI to the LI
12. Colonic bacteria in the LI converts conjugated bilirubin to UROBILINOGEN which is lipid soluble
13. 10-15% of urobilinogen is reabsorbed by the blood and taken back to the liver. 5% transported to kidneys and converted to yellow UROBILIN which is excreted in urine
14. 85-90% of urobilinogen is oxidised by other intestinal bacteria to STERCOBILIN which is a brown coloured pigment that colours the feces
26
what is the general aetiology behind jaundice?
excess bilirubin in the plasma
27
what are the three different classifications of jaundice?
- Prehepatic
- Hepatic
- Post hepatic
28
what is the pathology of pre-hepatic jaundice
produced by conditions where there is an excessive breakdown of erythrocytes (increased rate of haemolysis) which overwhelms the livers ability to conjugate
there is excess unconjugated bilirubin in the plasma
29
3 conditions that can cause pre-hepatic jaundice?
- malaria
- sickle cell
- thalassaemia
- Gilbert's syndrome
30
what is the pathology of hepatic jaundice?
biochemical reactions converting fat soluble into water soluble bilirubin may be affected by inflammatory change within the liver or necrosis
There is a build up of conjugated and unconjugated bilirubin in the blood (cannot conjugate as not enough cells, plus inflammation/cirrhosis may compress the intra-hepatic portions of the biliary tree causing some obstruction in excretion)
31
Name 3 causes of hepatic jaundice?
hepatitis
alcoholic liver disease
drug misuse (paracetamol overdoes)
primary biliary cirrhosis
32
what is the pathology behind posthepatic jaundice?
any obstruction of the biliary tree can produce jaundice
increase in conjugated bilirubin
33
3 causes of post hepatic jaundice?
gallstones
pancreatic cancer in the head of the pancreas (an obstructing tumour)
gallbladder / bile duct cancer
34
what are the features of pre-hepatic jaundice on the bowel
| ?
normal stools and urine
35
what are the features of hepatic jaundice?
- raised bilirubin in urine
- dark coloured urine
- normal stools
36
what are the features of post hepatic jaundice?
dark urine
pale stools
Conjugated bilirubin is water soluble, so is excreted in urine and makes it dark. Less conjugated bilirubin enters the gut and faeces become pale.
37
What are the general clinical features of jaundice?
Yellow skin and sclerae
| Itching
38
Investigations in jaundice patients
Underlying cause can be elicited from the history.
Liver Function Tests
Bilirubin
Albumin (marker of liver synthesis function)
AST and ALT (markers of hepatocellular inkjury)
Alkaline Phosphatase (raised in biliary obstruction)
Coagulation studies (prothrombin time can be used as a marker of liver synthesis function)
FBC (anaemia, raised MCV and thrombocytopenia seen in liver disease)
```
Ultrasound
Dilated bile ducts?
Gallstones?
Hepatic metastases?
Pancreatic mass?
```
MR Cholangiopancreatography used to visualise biliary tree in obstructive jaundice if US abdomen was inconclusive or limited.
39
Treatment of jaundice
Definitive treatment depends on the underlying cause
Symptomatic treatment is often needed for itching e.g antihistamines if not post-hepatic
Broad spectrum antibiotics if obstruction
Hydration
40
what are the functions of the liver?
Protein synthesis
Detoxification and excretion
Glucose and fat metabolism
Defence against infection (reticuloendothelial system)
41
how is liver injury classified and what does each entail?
- Acute (direct hit to the liver resulting in acute hepatocyte injury and death)
- Chronic (if the liver injury persists for more than 6 months. Can cause scarring and fibrosis which has the potential to result in liver failure)
42
Name three causes of acute liver injury?
- Viral hepatitis (A, B)
- EBV
- Glandular fever
- Drugs
- Alcohol
43
Name three causes of chronic liver injury?
- Autoimmune hepatitis
- Primary biliary cirrhosis
- Haemochromatosis
- Alcohol
- Viral hepatitis
44
Presentation of acute liver injury?
- malaise
- nausea
- anorexia
- jaundice
- sometimes liver pain
45
If the liver is inflamed where does pain radiate?
Right shoulder as inflammation of the liver may cause irritation to the diaphragm (phrenic nerve)
46
Presentation of chronic liver injury?
- peripheral oedema which can lead to ascites
- upper GI bleed
- Malaise, anorexia
- Wasting
- Bruising
- Itching
- Hepatomegaly
- Extensive spider naevus
47
what three liver function tests give index about liver function? What do they each mean?
Serum bilirubin
- usually all unconjugated
- in liver disease increased serum bilirubin
Serum albumin
- marker of synthetic function of the liver and useful for estimating the severity of chronic liver disease
Prothrombin Time
- marker of synthetic function of the liver
48
What are the liver function tests that give NO index of liver function?
serum liver enzymes
- Alkaline phosphatase
- Gamma-GT
- Alanine aminotransferase (ALT)
- Aspartate aminotransferases (AST)
49
what can an elevated Alk Phos show?
- May originate from the liver, bone or placenta
- Usually raised due to a disorder of the bone or liver
- Raised levels can also occur with hepatic infiltrations e.g mets
50
where is gamma-GT present in the body?
liver, pancres, renal tubules and intestine
51
what 2 other factors may be present which make it more likely that an elevated alkaline phosphate is caused by the liver?
- Raised Gamma-GT
| - Other raised liver function tests (serum albumin, bilirubin, prothrombin time)
52
when are transaminase enzymes seen in the blood?
usually these enzymes are contained in hepatocytes and leak into the blood with hepatocellular injury
53
when does liver failure occur?
when the liver loses the ability to regenerate or repair so that decompensation occurs.
Can be acute or chronic
54
causes of liver failure?
```
Infections
Viral hepatitis (B and C)
Cytomegalovirus
Epstein Barr Virus
Herpes Simplex Virus
```
```
Drugs
Paracetamol
Alcohol
Anti-depressant (amitriptyline)
NSAIDs
Cocaine
Antibiotics
```
Toxins
Vascular
Budd Chiari Syndrome
55
What is Budd Chiari Syndrome
Hepatic vein obstruction by thrombosis or tumour causes conjestive ischaemia and hepatocyte damage
56
Signs of liver failure
```
Hepatic encephalopathy
Jaundice
Abnormal bleeding: variceal bleeding
Small liver
Fever
Vomiting
Cerebral oedema
```
57
Why does liver failure cause encephalopathy?
Why can it also cause cerebral oedema?
ammonia builds up in the circulation and passes to brain. Ammonia = neurotoxic so can cause permanent brain damage. Stops the Kreb’s cycle causing neural cell death.
Astrocytes clear the ammonia to produce glutamine. Excess glutamine causes osmotic imbalance and cerebral oedema
58
What are the stages of hepatic encephalopathy?
I - sleep disturbance
II - drowsiness, confusion, behaviour change
III - restless, liver flap
IV - coma
59
Investigations in Liver Failure?
Bedside test for encephalopathy:
- Serial 7s
- Spell WORLD backwards
- Count as many animals in 1 min
- Draw a 5 pointed star
- Number connection test
Liver Function Tests
- Hyperbilirubinemia
- High serum ALT, AST
- Low coagulation factors (raised prothrombin time)
- Hypoalbuminemia
Bloods
High ammonia levels
Imaging
US - liver size
CXR
Doppler ultrasound to see hepatic vein patency
Microbiology (to rule out infection)
Blood culture
Urine culture
Ascitic tap
60
Management of liver failure?
Beware of sepsis, hypoglycaemia, GI bleeds.
Treat the underlying cause if known
Administer IV glucose if needed
Mineral supplements (calcium, potassium, phosphate)
Thiamine and folate supplements
Manage coagulopathy with IV Vitamin K, platelets, blood or fresh frozen plasma
Consider omeprazole as prophylaxis against ulceration and GI bleeds
Liaise with transplant centre
61
what is acute-on-chronic liver failure
acute decompensation of the liver caused by a failure of the liver to compensate for the functional overload resulting from the chronic liver disease
62
what is fulminant hepatic failure?
clinical syndrome defined as the rapid development of acute liver injury with severe impairment of the synthetic function and hepatic encephalopathy in a patient without obvious, previous liver disease
63
aetiology (3 causes) of fulminant hepatic failure?
drug induced liver failure (commonly paracetamol)
Viral hepatitis (B)
Vascular (Budd-Chiari Syndrome)
Wilson's disease (rare)
64
name 2 mechanisms by which drugs can cause liver damage?
1. disruption of intracellular Ca2+ homeostasis
2. Disruption of bile canalicular transport mechanisms
3. Induction of apoptosis
4. Inhibition of mitochondrial function, prevents fatty acid metabolism and accumulation of ROS
65
if they are going to, what is the time frame that drugs usually cause drug induced liver damage?
1-12 weeks
66
name two antibiotics known to cause jaundice?
Augmentin
Flucloxacillin
Erythromycin
67
pathophysiology of paracetamol overdose
- Too much paracetamol
- Increase in the cytochrome P450 metabolism pathway
- Increase in NAPQI
- Insufficient amount of glutathione stores
- Increase in unconjugated NAPQI which binds to hepatic macromolecules causing hepatocyte injury
68
Symptoms of paracetamol overdose?
Asymptomatic for the first 24 hours
```
Anorexia
Nausea
Vomiting
RUQ pain
Jaundice
Encephalopathy
```
69
Treatment for paracetamol overdose?
Activated charcoal for gastric decontamination
N acetyl Cysteine (NAC) to replenish glutathione stores
Supportive treatment
Liver transplant if severe
70
Pathophysiology of biliary colic
Temporary, severe abdominal pain caused by gallstones becoming lodged in the bile ducts.
After a meal, gallbladder contracts ejecting the gallstone into the cystic duct where it becomes stuck. Gallbladder continues to contract against the lodged gallstone. Can cause sudden, dull pain in the RUQ.
After 6 hours the gallstone usually dislodges, rolls back into the gallbladder and pain subsides
71
Aetiology of biliary colic (name 3)
```
Gallstones
Narrow Bile Duct
Pancreatitis
Duodenitis
Oesophageal spasms
```
72
name 4 risk factors that increase likelihood of developing gallstones
Fat
Female
Fertile
Forty
73
Symptoms of biliary colic
Sudden DULL pain in the RUQ which can radiate to the right shoulder
- Usually comes on after a meal or at night when lying flat
- Severity increases for 15 minutes then plateaus for 6 hours
Nausea
Vomiting
Sweating
Anorexia (because pain is so bad after eating)
74
Investigations and diagnosis of biliary colic
Diagnosis is based on recurring symptoms
Ultrasound of RUQ can show an obstruction
75
Treatment of biliary colic
Analgesic to manage pain and symptoms e.g opioid such as morphine
Cholecystectomy
76
what is a complication of biliary colic?
if the gallstone does not dislodge and stays in the cystic duct for prolonged periods of time it can lead to acute cholecystitis
77
what is cholecystitis defined as?
inflammation of the gallbladder
78
Pathology of acute cholecystitis
Person has gallstones in gallbladder
Small intestine secretes CCK → bloodstream → constricts the gallbladder to secrete bile
Gallbladder constricts
Gallstone becomes stuck in cystic duct, blocking the flow of bile
Gall bladder stretches and irritates the nerves of the gallbladder and cystic duct
Bile is in a state of stasis as it cannot exit the gallbladder.
Bile irritates the mucosa in the walls of the gallbladder to start secreting mucus and inflammatory enzymes which results in inflammation, distension and increasing pressure.
79
Name three possible progressions from acute cholecystitis
1. Stone falls out of cystic duct and symptoms subside
2. Pressure in gallbladder continues to increase, constricting the blood vessels which supply it. Leads to ischaemia and gangrenous cell death. Gallbladder has potential to rupture causing biliary peritonitis or sepsis.
3. Gallstone can get stuck further down the common bile duct. Block the flow of bile out of the liver. Increase in conjugated bilirubin in blood which can cause jaundice.
4. Cholangitis (bacterial growth)
80
aetiology of acute cholecystitis
gallstones stuck in cystic duct
81
Symptoms of acute cholecystitis
- Midepigastric pain
- Nausea
- Vomiting
- Anorexia
- Jaundice
- Low grade fever
82
Signs of acute cholecystitis? What is involved in each of these tests?
- Blumberg’s sign / rebound tenderness (RUQ pain when pressure is RELEASED from the abdomen)
- Positive Murphy’s sign (examiner places hand below the right costal margin after patient has exhaled- if patient suddenly stops breathing in due to the pain then this confirms diagnosis)
83
Investigations used in acute cholecystitis
What does each test show
Murphy’s sign
Imaging
- US : detect stones, gallbladder wall thickening, sludge (build up of substances in the gallbladder), distension of gallbladder or bile duct
- Cholescintigraphy : radiolabelled marker used to visualise the biliary system
- Endoscopic retrograde cholangiopancreatography
- MRCP to visualise biliary tree
LFTS
- Elevated ALP
- Elevated leukocyte count due to inflammation and CRP
- Raised serum bilirubin
84
Treatment options for acute cholecystitis
In 90% of cases the gallstone dislodges
Supportive :
IV fluids
Pain management (opiates)
IV antibiotics
Laparoscopic cholecystectomy
Stone dissolution : for (near) pure cholesterol stones can give oral ursodeoxycholic acid
Shock wave lithotripsy : shock wave directed onto gallbladder stones to turn them into fragments so they can be passed
85
Pathology of chronic cholecystitis
Constant state of gallbladder inflammation caused by recurrent obstruction of the cystic duct by a gallstone.
Chronic inflammation changes the gallbladder wall structure - damage to the epithelial cells. Can also lead to deep grooves and pockets of mucosa
86
What complication can arise due to chronic cholecystitis
Can lead to fibrosis and calcification of the epithelial tissue → porcelain gallbladder.
Gallbladder becomes hard and brittle with a bluish discolouration
87
Why is there calcification of the gallbladder in chronic cholecystitis
Calcification is caused by bile stasis, may cause calcium carbonate bile salts to precipitate out and deposit into walls.
88
Aetiology of chronic cholecystitis
Constant state of inflammation caused by recurrent obstruction of the cystic duct by a gallstone
89
Symptoms of chronic cholecystitis
- Midepigastric pain (DULL pain radiating to the right shoulder)
- Nausea
- Vomiting
- Anorexia
- Jaundice
- Low grade fever
- Distension
- Flatulence
90
Signs of chronic cholecystitis
Blumberg's sign
| Positive Murphy's sign
91
Investigations in chronic cholecystitis
Murphy’s sign
Imaging
US - sonographic murphy’s sign, detect stones, gallbladder wall thickening, sludge, distension
Cholescintigraphy : radiolabelled marker used to visualise the biliary system, if there is blocked duct the gallbladder cannot be seen.
92
Treatment of chronic cholecystitis
Laparoscopic cholecystectomy
93
Aetiology of gallstones (name three causes)
Obesity
Rapid weight loss: imbalance in bile composition leads to increased risk of calcium-bilirubin precipitation
Diabetes mellitus
Oral contraceptive pill : increase in oestrogen leads to an increase in bile and bile hypomotility
Liver cirrhosis
94
Risk factors (name 5) for developing gallstones
```
Female
Fat
Forty
Fertile
Smoking
OCP
Rapid weight loss
```
95
How are cholesterol stones made and what features do they have
- Cholesterol crystallisation in bile due to either a relative deficiency in bile salts and phospholipids or excess cholesterol (diabetes or hypercholesteraemia)
- not visible on X-ray
- Large, solitary
- Mainly cholesterol
96
What are two features of pigment gallstones ?
- small stones
- friable
- can be seen on X-ray
97
How are black pigment stones formed
excessive haemolysis leads to an increase in unconjugated bilirubin. Unconjugated bilirubin binds to calcium and precipitates out to form black pigment stones.
98
How are brown pigment stones formed
Caused by a gallbladder/biliary infection. Infectious organisms bring hydrolytic enzymes which hydrolyze conjugated bilirubin and phospholipids. Combines with calcium ions and precipitate out to form stones.
99
name one common infections that can cause brown pigment stone formation
E. coli
| Ascaris lumbricoides
100
complications that can be caused by gallstones
Cholecystitis
Ascending cholangitis
Blockage of common, pancreatic bile ducts
Gallbladder cancer
101
Symptoms of gallstones
May be asymptomatic
Sudden, intense abdominal epigastric pain that radiates to the right shoulder
Nausea, vomiting, jaundice, abdominal tenderness, distension, fever, chills, flatulence
102
What are the treatment options for gallstones?
Only if symptomatic!
Medial : bile salts to dissolve cholesterol stones
Surgery : cholecystectomy
Pain management
Lithotripsy
103
Investigations in suspected gallstones
Ultrasound
LFTs
Elevated bilirubin
Raised GGT, ALP, ALT and AST
104
what is ascending cholangitis
inflammation of the bile ducts from a bacterial infection
105
Pathology of ascending cholangitis
Flow of bile is blocked due to gallstones or a stricture
Bacteria can make its way from the duodenum up the bile duct and colonise the biliary system. Bacteria can continue to ascend and infect the stagnant bile as well as the surrounding tissue
106
Complications that can arise from ascending cholangitis?
| Why?
- sepsis --> multi organ failure
Bile duct is under high pressure from the obstruction. Can cause the spaces between the cells lining the ducts to widen, allowing the bacteria and bile to enter the bloodstream
107
Aetiology of ascending cholangitis
E. coli
Klebsiella
Enterococcus
108
Symptoms of ascending cholangitis
Biliary colic
Charcot’s triad
Fever
RUQ pain
Jaundice (dark urine and pale stools)
Reynold’s pentad
Charcot’s triad
Hypotension (caused by septic shock)
Confusion (caused by decreased blood flow to the brain)
109
Investigations in ascending cholangitis
Blood tests :
Increased WBC (FBC)
Increased CRP
LFTs
Elevated
Imaging
- Ultrasound
- Endoscopic retrograde cholangiopancreatography
- Abdomen CT can exclude carcinoma of the pancreas and makes it easier to spot pigmented stones causing an obstruction
110
What is an endoscopic retrograde cholangio-pancreatography?
Endoscope placed through mouth until get to the ampulla of Vater
Insert a cannula into the biliary tree and inject contrast material
X-rays taken to study the biliary tree
111
What is the management plan and the treatment options in ascending cholangitis?
Rehydration
IV antibiotics : piperacillin-tazobactam
Remove obstruction : ERCP, shockwave lithotripsy
Widen ducts with a stent if a stricture is the cause
Cholecystectomy is recommended to avoid future gallstone complications
112
What are the functions of the pancreas?
Endocrine : secrete glucagon and insulin
Exocrine: make digestive enzymes that are secreted into the duodenum and break down macromolecules. Made and stored as zymogens and activated by proteases.
113
what is acute pancreatitis
sudden inflammation and haemorrhaging of the pancreas
114
Name two risk factors for developing acute pancreatitis
Female
| Smoking
115
Pathology of acute pancreatitis
Caused by destructive effect of premature activation of pancreatic enzymes which causes pancreatic inflammation by the enzyme mediated autodigestion.
116
aetiology of acute pancreatitis - name 5 causes
I GET SMASHED
```
Idiopathic
GALLSTONES
ETHANOL ABUSE
Trauma
Steroids
Mumps
Autoimmune
Scorpion sting
Hypertriglyceridemia and hypercalcaemia
ERCP
Drugs
```
117
how does alcohol abuse lead to acute pancreatitis?
- alcohol increases zymogen secretion from acinar cells and decreases fluid and bicarbonate production from the ductal epithelial cells
- pancreatic juices become very thick --> potential blockage of pancreatic duct
- distension of pancreatic duct
- due to distension zymogen granules fuse with lysosomes bringing trypsinogen into contact with lysosomal digestive enzymes leading to autodigestion of the pancreas
118
how do gallstones lead to acute pancreatitis?
- Gallstone stuck in the sphincter of Oddi
- Blocks the release of pancreatic juices
- Intracellular Ca2+ increases and causes the early activation of trypsinogen
119
What complications can arise from acute pancreatitis
Pancreatic pseudocysts (form due to fibrous tissue surrounding the liquefactive necrotic tissue)
Haemorrhage
DIC
ARDS
120
Symptoms of acute pancreatitis
```
Nausea
Vomiting
Umbilical and flank bruising
Upper abdominal pain, radiation to the back which may be relieved by sitting forwards
Anorexia
Jaundice
Fever
```
121
Signs of acute pancreatitis
Hypocalcemia
Cullen’s sign (periumbilical region bruising caused as necrosis induced haemorrhaging spreads to soft tissue )
Grey Turner’s sign ; bruising around the flank
Abdominal pain, palpable tender mass
Dehydration
Hypotension
Tachycardia
122
Investigations for acute pancreatitis
Pain in epigastric region that radiates to back
Blood tests
Increase in serum amylase
Raised serum lipase
CT Scan of abdomen
Visualisation of inflammation, necrosis, pseudocysts
Ultrasound : looking for gallstones which may be the cause
Pancreatic scoring systems e.g APACHE II to assess severity
123
Treatment / management for acute pancreatitis?
Assess severity!
IV morphine
Hydration
Electrolytes
Nasogastric tube for dietary supplements to rest the bowels.
Urinary catheter
Treat any complications
Oxygen therapy
Antibiotics
If pancreatic necrosis suspected consider a laparotomy and debridement
124
what is chronic pancreatitis?
chronic, persistent inflammation of the pancreas often due to repeated episodes of acute pancreatitis
125
pathophysiology of chronic pancreatitis
Repeated episodes of acute pancreatitis lead to healthy pancreatic tissue being replaced by misshapen ducts, fibrinolytic tissue lay down by stellate cells and calcium deposits (these are caused by alcohol acute pancreatitis)
126
Aetiology of chronic pancreatits? (Name 5 causes) `
```
LONG TERM ALCOHOL EXCESS
Recurrent acute pancreatitis
Autoimmune
Smoking
Cystic Fibrosis
```
127
Clinical presentation of chronic pancreatitis
```
Pain in epigastric region
- Can radiate to back
- Often lasts for hours
- May be linked to meals
- May be relieved by sitting forwards or hot water bottles on the epigastric region/back
Bloating
Steatorrhoea
Weight loss
Nausea
Vomiting
Symptoms relapse and worsen
```
128
Investigations in chronic pancreatitis
Pancreatic biopsy
- Dilatation of pancreatic ducts
- Acinar cell atrophy
- Fibrosis
- Chronic inflammatory infiltrate
- Calcifications
```
Imaging
- Abdominal XRays
- Abdominal CT
- Abdominal US
- MRCP
May show calcifications with confirm diagnosis
```
129
Treatment / management for chronic pancreatitis
Analgesics for pain relief (coeliac plexus block)
No alcohol
Low fat diet
Give fat soluble vitamins and lipase
Insulin needs may be high or variable - beware of hypoglycaemia
Surgery is indicated in those with unremitting pain, narcotic abuse and weight loss e.g pancreatectomy or pancreaticojejunostomy
130
What is the pathology behind alcoholic liver disease?
Alcohol excess leads to increased metabolism via the alcohol dehydrogenase pathway to produce more acetaldehyde.
Causes increased fat production and abnormal lipid retention in the hepatocytes (steatosis) which leads to fatty liver.
Also form reactive oxygen species which lead to tissue injury and fibrosis.
Acetaldehyde can bind to macromolecules which the immune system recognises and attacks, sparking an immune response and causing alcohol hepatitis.
Continued alcohol excess can lead to cirrhosis.
131
What are the stages of alcoholic liver disease?
- Normal liver
- Steatosis (abnormal retention of lipids in hepatocytes)
- Fatty liver
- Alcoholic hepatitis (immune response, neutrophils destroy the hepatocytes)
- Cirrhosis
- Liver failure
132
Is there any point in the course of alcoholic liver disease that you can reverse the effects?
In the fatty liver stage, if you abstain from alcohol you can reverse the effects of fatty liver at this stage
133
What are mallory bodies?
Accumulation of protein bundles that are located in the cytoplasm of hepatocytes
134
What are 3 risk factors for developing alcoholic liver disease?
```
EXCESSIVE ALCOHOL CONSUMPTION (binging)
Glycogen storage disease
Female
Acute fatty liver during pregnancy
Malnutrition
Obesity
HIV
Hepatitis C
```
135
What happens when alcohol directly affects the stellate cells in the liver?
transformed into collagen producing myofibroblast cells
136
What is the clinical presentation of fatty liver?
Asymptomatic
May be some nonspecific abdominal symptoms e.g nausea, vomiting, diarrhoea due to the general effects of alcohol on GI tract
137
what is the clinical presentation of alcoholic liver disease?
```
Fatigue
Malaise
Dull RUQ pain
Anorexia
Bleeding
Mild jaundice (rarely presents)
Bruising
Other than that, patients may appear well with only a few of the above.
```
Ascites, hepatomegaly seen if there is significant damage in severe cases
May be features of alcohol dependency
138
What investigations would do in alcoholic liver disease?
Ultrasound
Blood tests (LFTs, FBC)
Liver biopsy
139
What would you see on ultrasound for each of the following stages of alcoholic liver disease:
1. Steatosis?
2. Fibrosis?
3. Cirrhosis ?
1. bright liver
2. coarse echo pattern
3. nodules and an irregular outline of the liver pattern
140
What will the LFTs show in someone with alcoholic liver disease?
What other results may show from other blood tests i.e FBC?
Raised AST and ALT (AST > ALT)
Elevated GGT
Elevated Alk Phos
Leukocytosis ( increased WCC)
May be thrombocytopenia and hypoglycaemia
141
What early changes can you see on a liver biopsy in someone with alcoholic liver disease?
Accumulation of membrane bound large droplet steatosis
| Proliferation of SER
142
What histological findings are present on a liver biopsy of a patient with alcohol hepatitis?
Neutrophils
| Mallory-Denk bodies
143
What histological findings are present in a patient with advanced alcoholic liver disease?
Fibrosis - accumulation of scar tissue
144
What is the treatment for alcoholic liver disease?
Stop drinking (if in fatty liver stage could reverse damage!)
Diet high in vitamins and proteins
Corticosteroids to suppress immune system - short term benefit in alcohol hepatitis
Alcohol cirrhosis : liver transplant! Patient will need to have shown commitment to giving up alcohol.
145
What are the characteristics of a fatty liver?
large
heavy
greasy
tender
146
Pathology of liver cirrhosis
Irreversible liver damage due to chronic scarring and damage to hepatocytes. It is end stage liver damage.
As fibrotic tissue builds up it compresses the sinusoids and separates the nodules, distorting the normal architecture of the liver and decreasing blood flow through the liver.
147
What changes to liver architecture occur in cirrhosis?
When hepatocytes are injured they form regenerative nodules and between these are fibrosed tissue. The formation of fibrotic tissue is mediated by stellate cells.
148
What is the consequence for the increased build up of fibrinolytic tissue
As fibrotic tissue builds up it compresses the sinusoids and separates the nodules, distorting the normal architecture of the liver and decreasing blood flow through the liver.
149
Aetiology of cirrhosis (name three causes)?
```
Chronic alcohol use
Chronic hepatitis C infection
Chronic hepatitis B infection
Autoimmune hepatitis
Hereditary haemochromatosis
Wilson disease
Alpha-1-antitrypsin deficiency
```
150
What possible complications can arise from liver cirrhosis?Name 5
Portal hypertension (which can lead to ascites)
Congestive splenomegaly
Renal vasoconstriction → hepatorenal failure
Decreased liver function (less detoxification)
Hepatic encephalopathy (asterixis, coma)
Increased oestrogen in blood
Gynecomastia
Spider naevus
Palmar erythema
Jaundice (increased unconjugated bilirubin in blood)
Hypoalbuminemia → oedema
Coagulopathy
Spontaneous bacterial peritonitis
151
What is the clinical presentation of liver cirrhosis?
| Early and late presentations?
Early - some fibrosis present
- Compensated so liver still does its job
- Liver may be slightly enlarged
- Asymptomatic
- Weight loss
- Weakness fatigue
Later - extensive fibrosis
- Jaundice
- Pruritus (itchy skin)
- Hepatic encephalopathy (confusion)
- Easy bruising (decreased clotting factors)
- Small liver
- Nail changes
- Muehrcke’s lines
- Terry’s nails (white proximally but distal ⅓ reddended)
- Clubbing
152
What investigations would you do in liver cirrhosis?
```
Liver biopsy is the gold standard!
LFTs
FBC
Ultrasound
MRI abdomen
Ascitic tap
```
153
What would you need to see on a liver biopsy to confirm a diagnosis of cirrhosis?
Microscopic appearance of hepatocytes (regenerating nodules) and fibrosis deposits between nodules
154
What would the LFTs show in a patient with cirrhosis
```
- LFTS may be normal OR
AST and ALT elevated AST > ALT
Raised ALP
Raised GGT
Raised bilirubin
Later with loss of synthetic function:
Decreased albumin, increased PT time, increased INR
```
155
What would an ultrasound show in a patient with liver cirrhosis?
(may show: small nodular liver, splenomegaly, reversed flow in portal vein)
156
Why do we do an ascitic tap in patients with liver cirrhosis?
Looking for neutrophils as may indicate spontaneous bacterial peritonitis
157
What is the treatment / management for cirrhosis?
Prevent continued liver damage by treating the underlying cause
Stop drinking
Antiviral medications for Hep C/B
Good nutrition
Avoid NSAIDs, opiates and sedatives
Fluid restriction for ascites, low salt diet
Liver transplant is the only definitive treatment for cirrhosis
158
what is the pathology of portal hypertension
Increased blood pressure in the hepatic portal venous system.
Caused by central veins and sinusoids become compressed and the pressure within the liver increases.
159
Portal hypertension can lead to what...? What implications does this have on liver function?
formation of portosystemic shunts where blood is diverted away from the portal venous system and backs up into the systemic veins.
Shunts cause decreased blood supply to the liver leading to decreased liver function and decreased blood detoxification
160
Name three complications that can occur due to portal hypertension?
Hepatic encephalopathy
Because the portosystemic shunts occur where the systemic and portal system connect, complications can arise at these locations
- Oesophageal varices
- Haemorrhoids
- Re- channel round ligament causing engorged superficial epigastric veins (caput medusae) across the umbilical area
Congestive splenomegaly
Ascites
```
ABCDE
Ascites
Bleeding
Caput Medusae
Diminished liver function
Enlarged spleen
```
161
Name two locations where the hepatic venous system can connect to the systemic venous system?
- inferior portion of the oesophagus
- superior portion of the anal canal
- round ligament of the liver
162
aetiology of portal hypertension
Pre-hepatic : portal vein obstruction e.g thrombus occluding the portal vein
Hepatic
CIRRHOSIS is the most common cause
Sarcoidosis - granulomas in liver
```
Post-hepatic:
Right sided heart failure
Constrictive pericarditis
IVC obstruction
Budd-Chiari syndrome
```
163
What are the symptoms of portal hypertension?
May be asymptomatic until complications occur.
Distended abdomen with ascites
Caput medusae
Signs that chronic liver disease is present
GI bleeding (haematemesis, melaena)
Jaundice
Hepatic encephalopathy
164
What investigations would you do in portal hypertension?
Ultrasound - detects nodules in cirrhosis
CT/MRI abdomen
Hepatic venous pressure gradient measurement (measure difference between pressure in the IVC and portal vein)
Blood tests
LFTs
FBC
Serology
Upper GI endoscopy - treat esophageal varices appropriately
165
Treatment of portal hypertension
Beta blockers to decreased portal venous pressure
Treat ascites with salt and fluid restriction and diuretics.
TIPS : transjugular intrahepatic portal venous shunt.
166
What is the TIPS procedure?
communication between portal vein and hepatic vein means that blood bypasses the liver circulation, reducing portal pressure
167
Pathology of varices
Submucosal dilation secondary to portal hypertension
168
Aetiology of varices?
Portal hypertension
169
Risk factors for variceal bleeds?
Variceal size
Endoscopic features of the variceal wall
Advanced liver disease (coagulopathy)
170
Signs of variceal bleed?
Haematemesis
171
Initial management of bleeding varices?
1. Resus until hemodynamically stable
2. High flow oxygen
3. IV fluids
4. Blood transfusion if anaemia
5. Correct any clotting abnormalities (Vitamin K, platelet transfusion)
6. IV terlipressin to cause vasoconstriction
7. Endoscopic banding (oesophageal)
8. Sclerotherapy (gastric)
If banding fails then balloon tamponade
172
Name 2 methods of primary prevention of varices?
```
Beta blocker (propranolol)
Repeated variceal banding
```
173
One method that is used in secondary prevention of variceal bleeds?
TIPS
174
What are 4 causes of acute hepatitis?
Hepatitis virus A-E
Epstein Barr virus
Cytomegalovirus
Toxoplasmosis
175
What is the pathology of hepatitis A virus?
Always an acute infection
Short incubation period of 2-6 weeks
The virus replicates in the liver and attacks the hepatocytes.
It is excreted in the bile then excreted in the faeces for 2 weeks before the onset of symptoms
176
What is the transmission of hepatitis A virus?
Ingestion of contaminated food or water e.g shellfish
Faecal-oral route of transmission
177
Name 3 risk factors that can increase a person's likelihood of developing hepatitis A virus?
Overcrowding and poor sanitation facilitate its spread
Travellers
Food handlers
Shellfish
178
What are the symptoms of Hepatitis A? What other symptoms occur after 1-2 weeks of the disease onset?
```
Fever
Malaise
Anorexia
Nausea
Arthralgia
```
Then (after 1-2 weeks) may present with…
Jaundice (dark urine and pale stools)
Hepatosplenomegaly
Adenopathy (enlarged lymph nodes)
179
What investigations would you do for hepatitis A ?
Liver function tests
Serology for diagnosis
Full blood count
180
What would the liver function tests show in a patient with hepatitis A virus?
AST and ALT rise 22-40 days after exposure and return to normal over 5-20 weeks
181
What are you looking for in the serology test in hepatitis A patients?
IgM antibody rises from day 25 (indicating an active infection)
IgG is detectable for life
182
How can a person have IgG antibodies against hepatitis A?
After an initial infection
| Vaccination
183
What could the FBC show in a patient with hepatitis A?
Leucopenia
184
How can you prevent hepatitis A?
Active immunisation for inactivated viral protein
185
What is the treatment for hepatitis A?
Supportive therapy
Avoid alcohol
186
What type of virus is hepatitis A?
RNA virus
187
What type of virus is hepatitis B?
DNA virus
188
What type of infection can hepatitis B be?
Can be an acute and chronic infection, only moves onto chronic in 20% of cases
189
What is the transmission of hepatitis B?
Via the blood
190
Name 5 routes of transmission for hepatitis B?
Unprotected sex
IV drug users
Direct blood-blood contact e.g needlestick injury
Blood products
Tattoos
Vertical transmission - mother to child in utero or soon after birth
191
Name three groups of people who are at a higher risk of catching hepatitis B?
```
IVDU and their sexual partners/carers
Health workers
Haemophiliacs
Men who have sex with men
Close family members of a carrier
CKD/dialysis patients
```
192
What are the symptoms of hepatitis B?
Infection can be subclinical (asymptomatic)
```
Viraemia
Non-specific symptoms such as…
Nausea
Malaise
Anorexia
Arthralgia
```
May have rashes urticaria
After 1-2 weeks patients can become jaundiced
Hepatosplenomegaly
193
Name 2 complications that can arise from hepatitis B?
Fulminant hepatic failure
Cirrhosis
Hepatocellular carcinoma
194
What two investigations would you do for hepatitis B?
Liver function tests (are raised in the acute phase)
SEROLOGY
195
What are the three markers we look for in serology of a hepatitis B patient?
HBV surface antigen : HBsAg
HBV core antigen : HBcAg
E antigen : secreted by infected hepatocytes (this is a marker than infection is actively happening)
196
If there is E antigen and viral hepatitis B DNA in the serum what does that indicate?
That the virus is active and is replicating and infecting hepatocytes
Acute infection
197
What would the serology show if a patient had an acute hepatitis B infection?
HBsAg and HBcAg are positive
Viral DNA is present in the blood
E antigen is present in the blood
Immune system produced IgM antibodies against HBcAg
198
What is 'the window' in the context of hepatitis B serology?
Cannot detect HBsAg or IgG against HBsAg as they are both to low.
This can last for several weeks → months
Can detect IgM antibodies against HBcAg
199
What are the following two options following on from the window in terms of serology of a hepatitis B patient?
1. IgG > HBsAg (no more infection)
2. IgG < HBsAg (not enough IgG for surface antigens)
If option 2 occurs then patient is still infected with the virus and it becomes a chronic infection which leads to continuing hepatocellular damage
200
What are the two different types of serology in a chronic hepatitis B infection?
How can the host present (2 different ways)
1) Host presents healthy.
- HBsAg are present (for more than 6 months = carrier status)
- IgG for core antigen (HBcAg)
- NO DNA or e antigen
- Host is still contagious but there is a decreased risk
2) Host is infective
- HbsAg, HBcAg, DNA and E antigen all present
- IgG for core antigen is overwhelmed
- Increased risk of cirrhosis and hepatocellular carcinoma
201
If you are immunised against hepatitis B what antibodies do you have circulating?
IgG antibodies against HbsAg so you have protection
202
What is the treatment for hepatitis B?
Avoid alcohol
Immunize sexual contacts
Refer all those with chronic liver inflammation, cirrhosis or high viral load for antivirals
- 48 weeks of pegylated interferon alfa-2a
- Or nucleoside analogues
These inhibit viral replication
May be life long as does not stimulate an immune response
Entecavir, tenofovir
203
What type of virus is hepatitis C?
RNA flavivirus
204
What type of infection is hepatitis C usually?
Chronic
205
What can hepatitis do which means that it is more likely a chronic infection?
Virus often mutates rapidly to bypass the host immune system
206
how is hepatitis C transmitted?
Via the blood
207
Name 4 ways in which hepatitis C can be transmitted?
Childbirth (rare)
Unprotected sex
IV drug users
Transfusion
208
What is the main symptom of hepatitis C?
Asymptomatic
Chronic infection often goes unrecognised for 10-20 years unless identified when having LFTs performed
209
What symptoms may chronically infected patients with hepatitis C experience?
Malaise
Weakness
Anorexia
210
What tests should you perform in hepatitis C?
| What may they show?
Liver function tests
- persistently elevated or fluctuating liver enzyme levels
Enzyme immunoassay
- screen for HCV IgG antibody
HCV RNA test using PCR
- gold standard for diagnosis
- detects the levels of viral RNA in the blood
HIV test
211
What is the treatment for Hepatitis C virus?
Quit alcohol
Antiviral combination therapy
s/c injections of pegylated interferon alpha and daily oral doses of oral ribavirin
Liver transplant is the treatment of choice for people with end-stage liver disease
212
What type of virus is Hepatitis D?
Incomplete RNA virus
213
What does hepatitis D virus need to infect a host? Why?
Needed to have had hepatitis B for assembly. Virus is unable to replicate on its own, it is activated by the presence of hepatitis B.
214
What are the two different types of infection in hepatitis D? Which is more severe?
Co-infection
Hepatitis B and D infect the host both at the same time
Clinically indistinguishable from acute HBV infection
Super-infection
More severe
Host has chronic HBV (usually dormant) and then gets HDV
Secondary acute hepatitis and increased rate of liver fibrosis progression
Increases the risk of fulminant hepatitis/hepatocellular carcinoma
215
How is hepatitis D transmitted? Name 4 ways it can be transmitted?
Transmitted via the blood
Unprotected sex
IV drug users
Direct blood-blood contact e.g needlestick injury
Blood products
Tattoos
Vertical transmission - mother to child in utero or
216
Name 3 symptoms of hepatitis D?
Infection can be subclinical (asymptomatic)
```
Viraemia
Non-specific symptoms such as…
Nausea
Malaise
Anorexia
Arthralgia
```
Hepatosplenomegaly
217
What tests would you do for hepatitis D?
Liver Function tests
Serology
Serum IgM anti-HCV in the presence of IgM anti-HBV confirms the co-infection
218
What is the treatment for hepatitis D?
Subcutaneous pegylated interferon-alpha 2a
219
What type of virus is hepatitis E?
RNA virus
220
What type of infection does hepatitis E cause?
acute infection
221
What is the transmission of hepatitis E virus?
Undercooked seafood
Contaminated drinking water
Faecal-oral route
222
What are the symptoms of hepatitis E?
```
Acute self-limiting disease
Fever
Malaise
Anorexia
Nausea
Arthralgia
```
Then (after 1-2 weeks) may present with…
Jaundice (dark urine and pale stools)
Hepatosplenomegaly
Adenopathy (enlarged lymph nodes)
223
What investigation would you do for hepatitis E?
Serology
HEV IgM = active infection
HEV IgG antibody = recovery (NO vaccination)
224
Name 2 things you can do to prevent being infected with hepatitis E?
Good food hygiene and sanitation
| Avoidance of tap water in high risk areas
225
What is the treatment for hepatitis E ?
Supportive treatment
226
Aside from viral causes, name 3 other causes of chronic hepatitis?
Alcohol
Autoimmune
Drugs
227
What is autoimmune hepatitis?
Inflammatory liver disease of unknown cause characterized by abnormal T cell function and autoantibodies directed against hepatocyte surface antigens
228
What is the aetiology of autoimmune hepatitis?
Unknown
229
What are the symptoms of autoimmune hepatitis?
```
Acute hepatitis and signs of autoimmune disease (40%)
Fever
Malaise
Urticarial rash
Polyarthritis
Pulmonary infiltration
```
Gradual jaundice
Asymptomatic
Diagnosed incidentally with chronic liver disease
Amenorrhoea
230
What tests would you do for autoimmune hepatitis?
Liver function tests
Serology
Full blood count (looking for signs of hypersplenism)
Liver biopsy
231
What would the liver function tests show in autoimmune hepatitis?
Elevated serum bilirubin
Elevated AST
Elevated ALT
Elevated ALP
232
What would serology show in a patient with autoimmune hepatitis?
Hypergammaglobulinaemia (IgG)
| Positive autoantibodies
233
What results from a FBC show indications of hypersplenism?
Anaemia
Decreased WCC
Decreased platelets
234
What is diagnosis based on in autoimmune hepatitis?
depends on excluding other disease
235
what is the treatment for autoimmune hepatitis
immunosuppressant therapy
- prednisolone
- azathioprine
Liver transplant is indicated for decompensated cirrhosis or if there is failure to medical therapy
236
What does Epstein Barr Virus cause ?
Infectious mononucleosis is
237
What type of virus is the epstein barr virus?
Human herpesvirus 4
238
What is the pathology of epstein barr virus
The virus targets the circulating B lymphocytes and squamous epithelial cells of the oropharynx
239
What are the symptoms of epstein barr virus in childhood infection?
Usually asymptomatic infection in childhood
240
What are the symptoms of infectious mononucleosis ?
```
Fever
Anorexia
Lymphadenopathy
Palatal petechiae
Splenomegaly
Hepatomegaly
```
Jaundice
Malaise
Resolution of symptoms in 2 weeks
241
What investigations do you do for EBV?
blood film
Heterophile antibodies and antibody tests
Serology
242
What would the blood film show in a patient with EBV?
```
Lymphocytosis
Atypical lymphocytes (large, irregular nuclei)
```
243
What would the serology show in a patient with EBV?
IgM to EBV capsid antigen in acute infection
| IgG if previous infection
244
What is the treatment for an EBV infection?
Supportive
245
Define diarrhoea?
Passage of three or more loose or liquid stools per day (increased frequency and volume and decreased consistency)
246
Name three types infective causes of diarrhoea?
```
Rotavirus
Shigella
Salmonella
E.Coli
Hepatitis A and E
Vibrio cholerae
Norovirus
Clostridium difficile
```
247
What patients are most likely to develop diarrhoea caused by vibrio cholerae
Travellers
248
What is the route of transmission of C.diff
Faeco-oral route of transmission directly or through spores in the environment
249
what is C.diff infection associated with?
Associated with antibiotic use (especially broad spectrum antibiotics)
250
What are the signs that a patient has a C.diff infection?
```
Increasing temperature
Colic
Diarrhoea with systemic upset
- High CRP
- High WCC
- Decreased albumin
Colitis
Stool has a characteristic smell
```
251
What investigations would you do for C.diff?
Stool microscopy, culture
- Rapid screening test for C.diff toxin
- Can culture to identify the strain
Tissue samples obtained at sigmoidoscopy
252
What is the treatment for mild C.diff disease?
Stop causative antibiotic if possible
metronidazole
253
what is the treatment for severe C.diff disease?
Stop causative antibiotic if possible
vancomycin
254
What is the treatment for recurrent C.diff disease?
fidaxomicin or faecal transplant
255
How do you prevent the spread of C.diff?
Hand washing with soap to kill spores
256
What is Wilson's disease?
disorder of copper excretion with excess deposition in liver and CNS (e.g basal ganglia)
257
What is the pathology of Wilson's disease?
In normal physiology the copper is normally absorbed from the stomach and excreted in bile
In Wilson’s the excretion process is impaired leading low serum concentrations of copper and hepatic retention of copper leading to liver injury.
258
What is the aetiology of Wilson's disease?
Mutations in the ATP7B gene located on chromosome 13
This gene encodes a P-type adenosine triphosphate (Wilson’s ATPase)
It functions within hepatocytes to move copper across intracellular membranes
259
What is the pattern of inheritance for Wilson's disease?
Autosomal recessive inheritance
260
Name one risk factor that increases your chances of having Wilson's disease?
Family history
261
When does Wilson's disease typically present?
Second and third decades of life
262
What is the main difference in how children and young adults tend to present with Wilson's disease?
Children tend to present with liver disease (hepatitis, cirrhosis, fulminant liver failure)
Young adults tend to present with CNS signs - most commonly an early sign is an asymmetric tremor
263
What symptoms suggest Wilson's Disease?
```
Asymmetric tremor
Depression/mania episodes commonly present
Labile emotions
Personality change
Decreased memory
Slow to solve problems
Kayser-Fleischer Rings
Haemolysis
Blue nails
Arthritis
Hypermobile joints
```
264
What are Kayser-Fleischer Rings
Copper rings in the iris
265
What tests would you do in a patient with Wilson's disease to diagnose?
```
Urinalysis
LFTs
Serum copper
Liver biopsy
MRI
Molecular genetic testing can confirm a diagnosis
```
266
What would urinalysis show in a patient with Wilson's disease?
24hr copper excretion is high
267
what level of serum copper could suggest Wilson's disease?
< 11μmol/L
268
What would the liver biopsy show of a patient with Wilson's disease?
Increased hepatic copper
269
What is the treatment for Wilson's disease?
```
Diet
Avoid foods with high copper content:
Liver
Chocolate
Nuts
Mushrooms
```
Drugs
Lifelong chelating agent penicillamine
Liver transplant if severe liver disease
Screen siblings as asymptomatic homozygotes need treating
270
What drug do you prescribe for a patient with Wilson's disease?
Penicillamine
271
What is alpha-1-antitrypsin ?
| What is its normal action
A1AT is a serine protease inhibitor that controls inflammatory cascades and its main function is to balance the action of neutrophil-protease enzymes in the lungs
272
What is the pathology of alpha-1-antitrypsin deficiency?
Protein is produced but the molecular configuration is changed so it cannot pass out of the liver. Cannot pass to the lungs and liver disease develops because of the congestion of A1AT in hepatocytes which leads to cell destruction.
273
Aetiology of alpha-1-antitrypsin deficiency?
```
Mutation in SERPINA1 gene on chromosome 14
Genetic variants are :
PiMM (normal phenotype)
High risk phenotypes are
PiSZ
PiZZ
```
274
What are the symptoms of alpha-1-antitrypsin deficiency?
Lungs
Dyspnoea from emphysema
Wheezing
Cough
Liver
Cirrhosis
Cholestatic jaundice
275
What tests would you do for alpha-1-antitrypsin deficiency?
Serum A1AT levels are low
Lung function tests
Reduced FEV1 with an obstructive pattern
Liver biopsy
Phenotyping
SZ
ZZ
276
What is the management for alpha-1-antitrypsin deficiency?
Stop smoking
Treatment/preventative vaccination for lung infections
Monitor liver function
Liver transplant if severe
Manage emphysema
277
What are the most common liver tumours?
Metastases
| from breast, bronchus or GI tract
278
What is the most common type of primary liver cancers?
Hepatocellular carcinoma
279
Name three causes of hepatocellular carcinoma?
```
Hepatitis B virus
Hepatitis C virus
Autoimmune hepatitis
Cirrhosis
Non-alcoholic fatty liver
```
280
What are the symptoms of hepatocellular carcinoma?
```
Fever
Malaise
Anorexia
Weight loss
RUQ pain
```
281
What are the signs of hepatocellular carcinoma?
Hepatomegaly (smooth or hard and irregular)
Signs of chronic liver disease
Feel for an abdominal mass
282
What tests would you do to diagnose hepatocellular carcinoma?
Imaging
3 phase CT
MRI - better at distinguishing benign from malignant tumours
```
Bloods
FBC
Blotting
LFTs
Serum alphafeto-protein may be raised
```
Biopsy
Confirm histological diagnosis
283
What is the treatment for hepatocellular carcinoma?
Resecting solitary tumours
Liver transplant
284
How can you prevent the likelihood for developing hepatocellular carcinoma?
HBV vaccination
Don’t reuse needles
Screen blood
285
What is cholangiocarcinoma?
Biliary tree cancer
Usually slow growing
Most are distal extrahepatic or perihilar
286
Name three causes of cholangiocarcinoma
Flukes (parasitic worms)
Primary sclerosing cholangitis
Biliary cysts
287
Name 3 symptoms of cholangiocarcinoma?
```
Fever
Abdominal pain (localised to RUQ)
There may be ascites
Malaise
Jaundice
```
288
What tests would you do in cholangiocarcinoma?
LFTs
CT scan
Contrast MRI
Biopsy
289
What would the LFTs show in a patient with cholangiocarcinoma?
Elevated conjugated bilirubin
| Markedly elevated ALP, GGT
290
What are the treatment options for cholangiocarcinoma?
Complete surgical resection (only intervention that offers a cure)
70% are inoperable at presentation
Adjuvant chemotherapy
Radiotherapy
Stenting to relieve symptoms
291
Name two benign liver tumours?
haemangiomas
| Hepatic adenma
292
Name 4 cancers that commonly metastasise in the liver?
colon
breast
stomach
lung
293
What are the majority of pancreatic carcinomas?
Most are ductal adenocarcinomas (exocrine)
Majority arise in the pancreatic head
294
Name 5 risk factors for developing pancreatic carcinoma?
```
Smoking
Alcohol
Carcinogens
Diabetes
Chronic pancreatitis
Increased waist circumference
High fat and red or processed meat diet
Family history
```
295
What is the typical patient who has pancreatic carcinoma?
Male and over 70 years old
296
What are the symptoms of pancreatic carcinoma?
| What symptoms can suggest if the cancer is in the head or the body of the pancreas?
Anorexia
Weight loss
Diabetes
Acute pancreatitis
If in the head of the pancreas
- Painless obstructive jaundice
If in the body or tail of the pancreas
- Epigastric pain that radiates to the back and is relieved by sitting forwards
297
What are the signs of pancreatic carcinoma?
```
Jaundice + palpable gallbladder
Epigastric mass
Hepatomegaly
Splenomegaly
Ascites
```
298
What tests would you do for pancreatic canrcinoma?
Blood
Imaging
- US or CT scan
Biopsy
299
What may you see on a CT scan of someone with pancreatic carcinoma?
a pancreatic mass +/- dilated biliary tree +/- hepatic mets
300
What are the treatment options for pancreatic carcinomia?
Surgery
Pancreatoduodenectomy (Whipple). Best considered only where no distant metastases and where vascular invasion is still at a minimum
Post operative chemotherapy delays disease progression
Palliative therapy
Opiates for pain
Palliation of jaundice using stenting
301
What is ascites?
Accumulation of free fluid in the peritoneal cavity
302
Name 5 causes of ascites?
```
Local inflammation
Low protein
Low fluid
Neoplasia
Pancreatitis
```
303
Why does low protein cause ascites?
Causes inability to pull fluid back into the intravascular space
Raises pressure in vessels causing fluid to leak out of vessels
304
Why does low fluid cause ascites?
Seen in cirrhosis, Budd-chiari syndrome, cardiac failure
Leads to increase RAAS
Portal hypertension which leads to ascites
305
Name 5 symptoms of ascites
Distended abdomen
Abdominal swelling that may develop over several days or weeks
Fullness in the flanks and shifting dullness
Mild abdominal pain and discomfort are common
If there is severe pain consider bacterial peritonitis
Respiratory distress and difficulty eating
May be scratch marks on abdomen caused by itching due to jaundice
Peripheral oedema
306
What are symptoms of ascites?
Presence of fluid is confirmed by demonstrating shifting dullness
Diagnostic aspiration of 10-20ml of fluid using ascitic tap
Protein measurement of ascitic fluid
Transudate - low protein
Exudate - high protein
307
What do you test for in ascites in the ascitic tap?
Raised WCC
Gram stain and culture
Cytology to find malignancy
Amylase to exclude pancreatic ascites
308
What are the treatments of ascites?
Treat the underlying cause
Fluid and salt restriction
Drink no more than 1.5L a day
Restrict dietary salt
Diuretics
Spironolactone +/- furosemide
Large-volume paracentesis and albumin
Perforation of a cavity to remove fluid
May need to give albumin to replace the loss from ascites to prevent reaccumulation of ascites
309
What treatment would you do for resistant ascites?
Trans-jugular intrahepatic portosystemic shunt
310
What are the anatomical limits of the foregut?
Lower oesophagus to D2 (liver, spleen and gallbladder)
311
Where would you feel pain if there was pathology in the foregut?
Epigastric
312
What are the anatomical limits of the midgut?
D2 to 2/3 across transverse colon (majority of the abdomen)
313
Where would you feel pain if there was pathology in the midgut?
Periumbilical
314
What are the anatomical limits of the hindgut
Transverse colon to upper rectum
315
Where would you feel pain if there was pathology in the hindgut?
Hypogastric
316
What is the innervation of the parietal peritoneum?
somatic innervation
| sensation is well localised
317
What is the innervation of the visceral peritoneum?
Autonomic innervation
| Sensation is poorly localised
318
What is peritonitis?
Inflammation of the peritoneum
319
What are the differences between primary and secondary causes of peritonitis?
Primary
- Inflammation on its own
- Spontaneous Bacterial Peritonitis
Secondary
- Non-bacterial causes e.g bil
320
What are the bacterial causes of peritonitis?
Gram negative
- E.coli
- Klebsiella
Gram positive
- Staphylococcus aureus
Can result in peritonitis either through irritation of the peritoneum (perforated appendix or spontaneous bacterial peritonitis)
321
What are the chemical causes of peritonitis?
Bile
Old Clotted blood
Chemical irritation due to leakage of intestinal contents
Ruptured ectopic pregnancy
322
What are the symptoms of peritonitis?
Perforation
Acute sudden onset of pain followed by general collapse and shock
If secondary to inflammatory disease the onset is less rapid with the initial features being those of the underlying cause
Lying still
Abdominal rigidity
Tenderness
323
What can relieve pain caused by peritonitis?
resting hands on the abdomen, stopping movement of the peritoneum and pain
324
Name a complication of peritonitis?
Sepsis
Local abscess formation
Kidney failure
325
What tests would you do for peritonitis?
Blood test
Monitor / confirm infection (raised WCC and CRP)
Serum amylase to exclude acute pancreatitis
HCG to exclude pregnancy
Ascitic tap and blood culture
Erect CXR may show gas under the diaphragm which can indicate bowel perforation
326
What is the treatment of peritonitis?
ABCs
Treat the underlying cause and treat early!
Nasogastric tube
IV fluids
327
What antibiotics would you use to treat spontaneous bacterial peritonitis?
cefotaxime and ceftriaxone
328
what is the difference between a reducible hernia and irereducible hernia?
reducible: can be pushed back into the abdominal cavity with manual manoeuvring
irreducible hernia: cannot be pushed back into place
329
what is an obstructed hernia?
intestine is obstructed within the hernia due to pressure from the edges of the hernia
330
what is an incarcerated hernia?
contents of the hernial sac are stuck inside by ashesions
331
what is a strangulated hernia?
blood supply is cut off resulting in ischaemia
332
What the two types of inguinal hernia and what are the differences?
Direct hernia
Peritoneal sac enters the inguinal canal through the posterior wall of the inguinal canal
Indirect hernia
Peritoneal sac enters the inguinal canal through the deep inguinal ring
333
Name three risk factors for inguinal hernia ?
```
Male
Chronic cough
Constipation
Urinary obstruction
Heavy lifting
Ascites
Past abdominal surgery
```
334
What is the presentation of an inguinal hernia?
Bulging associated with coughing or straining
Lump
Rarely painful
If painful - suggests strangulation
335
What are the treatment options for an inguinal hernia?
Wear a truss (surgical appliance to support a hernia - typically a padded belt) to contain hernia and prevent further progression
Surgery only if symptomatic
336
What is a femoral hernia?
Bowel enters the femoral canal below the inguinal ligament
337
Presentation of femoral hernia?
Mass in the upper medial thigh or above the inguinal ligament where it points down the leg
338
What is the treatment for a femoral hernia ?
Surgical repair
Herniotomy - ligation and excision of the sac
Herniorrhaphy - repair of the hernial defect
339
What is an incisional hernia?
Tissue protrudes through a surgical scar that is weak
| Follows the breakdown of muscle closure after a surgery
