HPB Flashcards
1
Q
What is jaundice?
A
= yellow discoloration of the sclera, skin and mucous membranes secondary to hyperbilirubinaemia.
2
Q
What is the normal range of bilirubin and at what value is jaundice typically clinically visible?
A
normal varies, but is typically from 3 – 21 mmol/L.
Generally the bilirubin needs to be around twice the upper limit (~40-50+) to be clinically visible.
3
Q
what is the cause of pruritus in jaundice?
A
generally due to excess bile salts in the skin rather than the bilirubin itself
4
Q
Physiology of bilirubin in the body
A
- Bilirubin is a product of haemoglobin breakdown. When a red cell is broken down (typically in the spleen), this releases unconjugated bilirubin (UCB).
- UCB is fat soluble and binds to albumin before being transported to the hepatocytes of the liver.
- In the liver it is conjugated by a hepatic enzyme. This conjugated bilirubin (CB) is then stored in the gallbladder as part of bile.
- Bile is released during digestion, where the CB is then broken down in the small intestine into Urobilinogen.
- Urobilinogen then takes 1 of 3 paths:
=> Converted to stercobilin in the gut and excreted in the stool
=> Absorbed into blood before being excreted by the kidney in the urine.
=> Recycled back to the liver to be re-excreted in bile.
5
Q
What are the 3 categories of causes of jaundice?
A
- Pre-hepatic
- Hepatic
- Post-hepatic
6
Q
What occurs in pre-hepatic jaundice?
A
Increased breakdown of RBCs leads to increased UCB – this overwhelms the capacity of the hepatocytes to conjugate it
=> There will be leftover UCB in the bloodstream and results in jaundice
7
Q
Causes of pre-hepatic jaundice
A
Severe Malaria
Pernicious anaemia
Sickle cell disease (these may die faster than normal RBCs)
Thalassaemia
Transfusion reactions
Autoimmune haemolytic anaemias
Gilbert’s Syndrome
8
Q
Gilbert’s Syndrome
A
= an autosomal recessive inherited condition – defective gene encoding for the hepatic conjugation enzyme.
Intermittent jaundice in the absence of haemolysis or underlying liver disease.
Will see isolated elevated UCB on investigation
Benign and self-limiting condition
9
Q
What occurs in hepatic/hepatocellular Jaundice?
A
Can be either:
- UCB not conjugated at a sufficient rate, leading to increased circulating UCB.
- A degree of obstruction means that CB not being transported into biliary ducts, CB builds up in the hepatocytes and ends up in the bloodstream (increased circulating CB).
10
Q
Causes of hepatic jaundice?
A
Viral hepatitis
Alcoholic hepatitis/cirrhosis
Drug-induced liver injury
- Paracetamol overdose
- Iatrogenic – e.g. flucloxacillin, co-amoxiclav, anti-epileptics
Autoimmune hepatitis
Wilson’s disease
11
Q
Wilson’s disease
A
very rare autosomal recessive disorder of copper metabolism.
Can result in excess deposition of copper in tissues.
Clinical sign – Kayser Fleischer rings
12
Q
What occurs in post-hepatic/Obstructive jaundice?
A
Blockage of the biliary tree obstructs drainage and causes bile (containing CB) to back up into the liver.
Pressure backs up bile between hepatocytes back to vasculature and CB is pushed back into the bloodstream (conjugated hyperbilirubinaemia).
13
Q
Causes of post-hepatic/Obstructive jaundice
A
Gallstones in common bile duct.
Cholangiocarcinoma
Strictures
Pancreatic cancer
Primary sclerosing cholangitis
Primary biliary sclerosis
Abdominal masses
Drug-induced cholestasis
14
Q
Pre-hepatic jaundice - urine and stool colour
A
Urine will be normal
Stools will be normal
15
Q
Hepatic jaundice - urine and stool colour
A
Urine will be dark
Stool may be slightly pale
16
Q
Post-hepatic jaundice - urine and stool colour
A
Urine will be dark
Stool will be pale
17
Q
What causes dark urine in jaundice?
A
Excess of conjugated bilirubin, which can be excreted in the urine
(Unconjugated cannot be excreted in the urine)
18
Q
What causes pale stools in jaundice?
A
Pale stools occur if conjugated bilirubin cannot be converted to stercobilin in the gut (i.e. if there is an obstruction preventing bile from reaching the intestine)
19
Q
What is Charcot’s Triad?
What typically causes this?
A
= jaundice, fever (usually with rigors), and RUQ pain
Indicates an ascending cholangitis
20
Q
DDx for jaundice with abdominal pain?
A
Pancreatitis, gallstones, ascending cholangitis
Sickle cell, drug-induced hepatitis, alcoholic hepatitis, viral hepatitis, cholangiocarcinoma, pancreatic cancer.
Haemolytic jaundices are classically painless, apart from sickle cell crisis.
21
Q
DDx for jaundice with fever?
A
Malaria (periodic fever; every third day) Viral hepatitis Cholangiocarcinoma Pancreatitis Ascending cholangitis
(Gallstones (only if infected))
22
Q
DDx for jaundice with weight loss?
A
Severe malaria, pernicious anaemia – loss of appetite.
Cholangiocarcinoma, pancreatic cancer
23
Q
DDx for jaundice and ETOH excess?
A
Alcoholic hepatitis – generally misuse over a long period of time, but also sometimes binge-drinking.
Pancreatitis
24
Q
DDx for jaundice and exotic travel?
A
Severe malaria
Viral hepatitis
25
DDx for jaundice and steatorrhoea?
Typically obstructive/post-hepatic cause – lack of bile in the intestines leads to less fat absorption
Can be intra-hepatic if there is cholestasis, but less common
26
What are signs of chronic liver disease on examination?
Spider naevi (>5, above the nipple line)
Palmar erythema
Clubbing
Bruising
27
What are caput medusae a sign of?
Portal hypertension
28
what is carotenaemia?
= increased beta-carotene levels in the blood.
This can occur following excessive consumption of carotene-rich foods, such as carrots, squash, and sweet potatoes.
Causes yellowing of skin but the sclera are spared - important to differentiate it from jaundice
29
Courvoisier’s Law
jaundice with a palpable (enlarged) but painless gallbladder suggests malignant obstruction of the biliary tree until proven otherwise
30
OE - nodular/decreased size of liver suggests...
cirrhosis
31
OE - Hepatomegaly sugests
malignancy or acute hepatitis
32
OE - enlarged spleen
malignancy or extravascular haemolysis
33
What investigations should be done in a jaundiced patient?
Observations
Full abdo exam
Urinalysis
FBC, CRP, LFTs, U&Es
Coagulation (liver synthetic function)
Lipase/Amylase
USS Liver/biliary tree?
34
what does raised ALP/GGT typically indicate?
biliary obstruction
35
what does raised ALT/AST typically indicate ?
hepatocellular damage
36
What would normal ALP/GGT and ALT/AST in a jaundiced patient suggest?
pre-hepatic cause
37
What are the two components of the spleen?
| What do they do?
* White Pulp: B + T cells within “screen” blood coming through for bacteria/viruses and attack or form antibodies against any they detect.
* Red Pulp: Filters out old/damaged red blood cells. Also a store for ~1/3 of your platelets.
38
Splenomegaly
= enlarged spleen
39
Hypersplenism
= overactive spleen
40
What are the causes of splenomegaly?
1. Increased Demand
2. Infiltration
3. Abnormal blood flow
41
What might cause increased demand of the spleen?
- Removal of defective RBCs – sickle cell, thalassaemia, spherocytosis
- Extramedullary haematopoiesis
- Infection – sepsis, EBV infection, AIDs, viral hepatitis, etc.
42
What might cause infiltration of the spleen?
- Malignant – most typically lymphomas, but also leukaemias and metastases
- Benign – cysts, haematomas
43
What might cause abnormal blood flow to the spleen?
- Vascular – portal/hepatic/splenic vein obstruction
| - Infection – hepatic schistosomiasis
44
Acute Pancreatitis
= acute inflammatory process involving pancreas.
can range from mild, self-limiting disease to complete necrosis of pancreas
occurs on a background of a normal pancreas and can return to normal (whereas chronic pancreatitis has irreversible changes).
45
Chronic Pancreatitis
= caused by progressive inflammation and irreversible damage to structure and function.
Alcohol abuse is most common cause for this
46
What are the two functions of the pancreas?
1. Endocrine - Alpha and beta cells
=> Secretes hormones like insulin and glucagon into the bloodstream for glucose homeostasis.
2. Exocrine - Acinar cells
=> Secrete amylases, lipases and proteases into the duodenum to aid digestion.
47
How does the pancreas protect itself from digestive enzymes?
1. Keeping the enzymes away from sensitive tissues in vesicles (zymogen granules).
2. Storing the enzymes as proenzymes (Zymogens) which first need to be activated by the protease trypsin.
=> Trypsinogen is needed to activate trypsin, which in turn activates zymogens
=> there are several trypsin inhibitors, which can bind to trypsin and inactivate it if it becomes prematurely active
48
Pathophysiology of acute pancreatitis
If trypsinogen is activated too early, this can lead to acute pancreatitis.
This might happen due to :
1. injury to acinar cells
2. due to impaired secretion of proenzymes into the duodenum
49
What are the 2 most common causes of acute pancreatitis?
1. GALLSTONES
| 2. ALCOHOL
50
Mnemonic for the causes of acute pancreatitis
"I GET SMASHED"
* I – idiopathic
* G – gallstones
* E – ethanol
* T – trauma (particularly puncture/stab wounds)
* S – steroids
* M – mumps
* A – autoimmune (e.g. SLE, Sjogrens)
* S – scorpion stings
* H – hyperglycaemia/hypertriglyceridaemia
* E – ERCP
* D – drugs (e.g. azathioprine, furosemide, immunosuppresants)
51
How does alcohol abuse cause acute pancreatitis?
With alcohol abuse, there is increased zymogen release from acinar cells. Alcohol also causes a decrease in fluids and bicarbonates in ducts.
This means pancreatic juices are thick and sludge-like (with many enzymes, but not much fluid) which can form a plug and block ducts.
=> Increase in pressure can cause distension of the ducts.
=> Distension can bring zymogen granules in contact with lysosomes which may contain digestive enzymes – can cause a cascade of pancreatic autodigestion.
=> In response to this, there is a release of cytokines, leading to an immune response.
52
How do gallstones cause acute pancreatitis?
With gallstones, they usually travel down the bile duct and get lodged at the Sphincter of Oddi, thereby blocking it.
This then becomes a similar situation to alcohol-induced acute pancreatitis where there is backing up to pancreatic juices.
53
Pancreatitis - clinical presentation
Nausea and Vomiting
```
Epigastric pain (with radiation to the back)
=> Sometimes relieved by sitting forward.
```
Cullen’s sign
Grey-Turner’s sign
Signs of sepsis – tachycardia, fever, rigid abdomen, shock.
54
Grey-Turner’s sign
Bruising around flanks
55
Cullen’s sign
Bruising around periumbilical region
56
Pancreatitis - investigations
1. Bloods:
- Amylase – usually elevated
- Lipase – these are elevated as well and are specific for pancreatitis
- Bone profile – to look at calcium levels (for hypercalcaemia)
- Triglycerides – to check for elevated triglyceride levels
(and do normal bloods such as FBC, U+Es, LFTs, CRP)
2. ABG – used for checking lactate and PaO2.
3. AXR – may show ileus
4. Abdo USS – used to confirm/exclude gallstones.
5. CT Abdo – not routine but can confirm diagnosis when uncertainty present.
57
Severity scoring in acute pancreatitis
Glasgow scoring system - a score above 3 is severe disease
```
P – PaO2 <8 kPa
A – Age >55
N – Neutrophils, WCC > 15x109/L
C – Calcium <2mmol/L
R – Renal, urea >16 mmol/L
E – Enzymes, LDH >600 IU/L or AST >200 IU/L
A – Albumin <32 g/L
S – Sugar, glucose >10 mmol/L
```
58
management of acute pancreatitis
Fluids – aggressive fluid resuscitation
Analgesia and antiemetics
NG tube
Adequate oxygenation
Antibiotics – if evidence of infection/necrosis
ERCP – if gallstone pancreatitis.
59
Why is fluid resuscitation important in pancreatitis?
Important to compensate for 3rd space losses
60
Complications of pancreatitis
Pancreas Pseudocyst/Abscess
Necrosis of pancreas
Hypovolaemic shock
Disseminated Intravascular Coagulation
Acute Respiratory Distress syndrome
61
Necrosis of the pancreas
The inflammatory process causes blood vessels to become leaky and then rupture, leading to pancreatic tissue swelling.
This causes premature activation of lipases which then starts to destroy peripancreatic fat.
The fat and tissues liquefy and can start necrosing (process called Liquefactive Haemorrhagic Necrosis)
62
how are pancreas pseudocyst and abscess formed?
what may the clinical presentation be?
When fibrous tissue surrounds necrotic tissues and fills with pancreatic juices.
The pseudocyst can also become infected to become an abscess and presents as sepsis.
This may cause abdominal pain, loss of appetite and a palpable tender mass.
63
what is the best way to assess for a pseudocyst/abscess of the pancreas?
Abdominal CT scan
64
Why can ARDS occur in pancreatitis?
massive inflammation => leaky blood vessels, which allows fluid to build up in the lungs and causes difficulty breathing.
65
What are the functions of the liver?
Storage of iron, copper, and vitamins
Metabolism of drugs and alcohol
Metabolism of key nutrients
Synthesis of proteins (albumin, clotting factors, complement, transferrin)
Excretion (bile and bilirubin)
66
How does the liver metabolise key nutrients?
Carbohydrates – storage as glycogen when fed, release of glucose when fasting.
Fat – produces and processes circulating lipoproteins
Protein – processes digested amino acids
67
What is acute liver failure?
= sudden impairment of a previously healthy liver.
68
What is acute on chronic liver failure?
= decompensation of chronic liver disease
69
What is fulminant liver failure?
= sudden massive necrosis of liver cells with severe impairment of liver function
70
Clinical features of liver failure
Abdominal pain
Fatigue
Nausea
Symptoms related to complications
Jaundice
Ascites
Liver flap
Signs of pre-existing liver disease (in acute on chronic failure)
71
Complications of liver failure
Bleeding
Spontaneous Bacterial Peritonitis
Hypoglycaemia
Hepatic encephalopathy
72
Why can there be increased bleeding in liver failure?
Reduced production of clotting factors by the liver, combined with the presence of oesophageal varices in chronic disease, creates a risk of massive oesophageal haemorrhage.
73
Spontaneous Bacterial Peritonitis
In ascites, presence of static fluid in the peritoneum promotes bacterial growth and leads to sepsis.
74
Why can there be hypoglycaemia in liver failure?
The liver is not effectively performing its usual function of releasing glucose when fasting
75
Hepatic encephalopathy
= a collection of neuro-psychiatric symptoms in a patient with decompensated liver disease
In decompensated cirrhosis, the liver is not able to clear ammonia produces by the bowels, so the level in the blood rises
Ammonia crosses the BBB and is processed by astrocytes into glutamine. Accumulation of glutamine creates osmotic imbalance and fluid moves into the cells – this is cerebral oedema, and it impairs normal functioning of the brain
76
Aims of treatment of liver failure
Depends on the cause
Prevention of further damage (e.g. stop alcohol)
Symptoms may be managed without curing the disease
Potentially liver transplant, depending on circumstances
77
what are the most common drugs causing liver injury?
paracetamol
Abx - flucloxacillin / co-amoxiclav
78
Which patients are more at-risk of a drug-induced liver injury?
Those who already have pre-existing liver damage, alcoholism or malnutrition.
79
Predictable vs idiosyncratic drug-induced liver injury
Predictable – reaction is dose-depended (e.g. paracetamol overdose)
Idiosyncratic – reaction is due to hypersensitivity in some patients
80
Paracetamol overdose
Paracetamol is metabolised in the liver.
In the event of overdose, the metabolic pathways become overwhelmed and there is a build-up of intermediate compounds.
The compounds damage the cells, leading to cell death (acute liver necrosis), and potential liver failure
81
Acute vs long-term paracetamol overdose
deliberate massive overdose
=> after 24hrs there is a noticeable rise in AST and ALT, => after 48hrs there may be symptoms of jaundice and confusion.
This process is gradual in patients with a long term, low level overdose (e.g. accidentally taking too many paracetamol tablets daily for several weeks), but can be just as harmful.
82
What is hepatitis?
= inflammation within the liver
can be acute or chronic (inflammation persists for >6 months).
83
Acute causes of hepatitis
```
Hepatitis A-E
Other viruses – EBV, CMV, Yellow fever
Parasitic – malaria
Autoimmune
Drug reactions
Alcohol
```
84
Chronic causes of hepatitis
```
Hepatitis B +/- Hepatitis D virus
Hepatitis C virus
Autoimmune hepatitis
Alcohol
Hyperlipidaemia (NAFLD)
Drugs (methyldopa, nitrofurantoin)
```
Metabolic disorders (Wilson’s disease, alpha1-antitrypsin deficiency, haemochromatosis)
85
Pre-icteric phase of hepatitis
malaise, arthralgia, headache, anorexia, aversion to cigarette smoke, vague RUQ pain
86
Icteric phase of hepatitis
jaundice, dark urine, pale stools, pruritis, skin rash
87
What is the long-term outcome of chronic hepatitis?
will gradually progress to cirrhosis
an increased risk of hepatocellular carcinoma
88
Hepatitis A
Endemic in Africa and South America
Transmission is via the faecal-oral route and via shellfish.
Acute, often asymptomatic and naturally cleared (self-limiting)
Unlikely to progress to chronic infection.
On blood tests, the most notable feature is increased AST
Usually, no specific treatment needed
There is a vaccine available for travellers or those at high risk
89
Hepatitis B
Spread through bodily fluids – via blood or sex
Endemic in the Mediterranean, Far East, and Africa
Hepatitis B vaccine is now given to all UK babies, also to unvaccinated adults who are at a high risk.
~10% will develop chronic disease, and ~1% develop fulminant liver disease
90
What are risk factors for Hepatitis B infection?
```
Sharing needles for IV drugs
Sex
Sharing toothbrush or razor
Needlestick injury
Bite injury
```
Babies of infected mothers (at birth)
Blood transfusion (UK blood is screened for Hep B to reduce this risk)
Dialysis patients (less common now)
Use of unsterilized equipment for tattoos, piercings, acupuncture, and dentistry
91
Hepatitis C
Spread via blood and sex – risk factors are the same as for Hepatitis B.
Early stages of infection are usually mild or asymptomatic
=> 85% of those infected will develop a chronic silent infection.
Chronic hepatitis C infection is one of the most common indications for liver transplant in the UK.
There is no vaccine available. As healthcare professionals, please wear PPE and do what you can to avoid needle stick injuries.
92
Hepatitis D
Spread via blood and sex
An incomplete RNA virus – on its own it cannot cause an infection.
=> To replicate, it relies on viral proteins from Hepatitis B.
Therefore Hepatitis B vaccination also confers immunity to Hepatitis D.
Hepatitis B+D infection further increases the risk of cirrhosis and acute liver failure
Transplant may be required
93
Hepatitis E
Spread via the faecal-oral route, shellfish, and undercooked pork
Endemic in Asia
Becoming more common: in the UK, Hepatitis E is now the most common cause of acute hepatitis
Usually causes a self-limiting acute infection
Unlikely to progress to chronic infection
There is no vaccine
94
Autoimmune Hepatitis
Most likely to affect those with other autoimmune conditions
May present with either acute or chronic hepatitis (more commonly chronic)
The presence of auto-antibodies will confirm the diagnosis (a blood test)
Treated with immunosuppressant therapy (e.g. prednisolone) long term, but liver transplantation may be required.
95
Presentation of autoimmune hepatitis
jaundice, fatigue, deranged LFTs
maybe also:
urticaria, polyarthritis, glomerulonephritis, amenorrhoea
96
Acute Alcoholic Hepatitis
Presents after a binge with jaundice, RUQ pain and systemic upset. There may be signs of chronic liver disease if it is acute on chronic presentation.
Bilirubin, prothrombin time and hepatic encephalopathy predict survival.
AST:ALT ratio of 2:1 suggests alcoholic liver disease.
97
Liver cirrhosis
= a progressive inflammatory fibrosis of the liver, resulting in loss of the normal hepatocellular architecture and appearance of small nodules of regeneration.
irreversible in later stages and the only potential cure is liver transplant.
Cirrhosis reduces life expectancy.
98
What can precipitate deterioration of liver cirrhosis?
* Alcohol binge
* Dehydration
* Infection
* GI bleed
* Surgery
99
What are some features of cirrhosis?
```
Hypoproteinaemia
Clotting problems
Portal hypertension
Oesophageal varices
Hyperaldosteronism
Hepatorenal syndrome
Ascites
Encephalopathy
```
100
Causes of cirrhosis
```
Viral hepatitis (B or C)
Alcoholism
NAFLD
Genetic Disorders
Autoimmune disorders
Drugs - e.g. amiodarone
```
101
Non-alcoholic fatty liver disease
Accumulation of fat within the liver.
Linked to obesity, diabetes, high cholesterol and more common in men
102
Primary Biliary Cirrhosis
Usually diagnosed by serology – presence of anti-mitochondrial antibody (~95% of cases)
Pathology – portal inflammation, damage to bile ducts and granulomas
103
Primary Sclerosing Cholangitis:
Best diagnosed by imaging (MRI or ERCP)
Pathology is patchy (hit and miss) – typically strictures in the bile ducts;
Strong association with ulcerative colitis;
Can go on to develop cirrhosis due to damage to the bile ducts;
High risk for bile duct cancer
104
Cirrhosis - Hypoalbuminaemia
Liver normally produces *all* serum albumin – it is not produced anywhere else in the body
Albumin is a carrier molecule for many other substances including hormones, drugs, and ions. It also helps to maintain osmotic pressure in the bloodstream.
In cirrhosis, the liver is not able to produce sufficient albumin
Hypoalbuminaemia can result in oedema in the legs, and contributes to development of ascites.
105
Portal Hypertension
The portal venous system drains blood from the intestines into the liver. Blood normally drains through the liver, then through the hepatic vein into the IVC.
Cirrhosis creates resistance and inhibits good blood flow through the liver
The blood flow backs up resulting in high blood pressure within the portal venous system and throughout the digestive tract.
Portal hypertension contributes to:
- Oesophageal varices
- Haemorrhoids
- Caput medusae – distension of superficial abdominal wall veins
106
Oesophageal Varices
Over time, veins become dilated and bulge into the lumen of the oesophagus
Pre-rupture, they are usually asymptomatic
Rupture of the varices can cause massive upper GI bleed – may be spontaneous or triggered by eating crunchy food
Emergency treatment is with band-ligation, performed by an endoscopist
107
Secondary Hyperaldosteronism in cirrhosis
Low serum albumin levels and portal hypertension together result in relative renal hypoperfusion.
Renal hypoperfusion activates the renin-angiotensin-aldosterone system, leading to increased levels of aldosterone. This causes sodium retention in the kidneys and subsequent water retention.
Water retention contributes to lower limb oedema and ascites
108
Hepatorenal Syndrome
Hepatorenal syndrome is renal failure in a patient with advanced cirrhosis
There is complex pathophysiology associated with renal hypoperfusion.
A sign of end-stage disease
109
Abnormal clotting in cirrhosis
Many coagulation factors are produced in the liver, and production is impaired in cirrhosis.
Portal hypertension changes the blood flow in the spleen and leads to hypersplenism and splenomegaly. The spleen breaks down platelets, and an over-active spleen will break down platelets faster than they are created.
110
Ascites
A combination of increased pressure in the portal venous system, hypoproteinaemia, and salt and water retention, cause a build-up of fluid in the peritoneal cavity.
The result is abdominal swelling and shifting dullness on examination.
The fluid is a transudate – i.e. low in protein (<30g/L)
Huge volumes of fluid can accumulate - limiting movement, eating, and causing breathing difficulties.
111
Management of ascites
* Fluid restriction and low salt diet
* Diuretics (furosemide and spironolactone)
* Large volume paracentesis
112
Stages of progression of encephalopathy
1. Subtle changes in behaviour, cognition, or sleep pattern
2. Drowsy, confused, slurred speech, personality change, may have liver flap
3. Stupor, incoherence, liver flap
4. Coma
113
How is hepatic encephalopathy managed?
Lactulose is given to promote bowel movements and to directly reduce bacterial production of ammonia in the bowel.
114
Signs of cirrhosis on examination
Leukonychia – white nails secondary to low albumin
Clubbing
Palmar erythema
Dupuytren’s contracture
Spider naevi
Caput Medusae
Xanthelasma
Gynaecomastia
Atrophic testes
Loss of body hair
Hepatosplenomegaly – then small, shrunken liver in later stages.
115
What imaging is used in cirrhosis??
Abdo USS
Sometimes MRI
AXR or CT are not routinely used due to exposure to x rays when they add no further info than USS.
116
What are some more specific tests that can be done in cirrhosis?
Fibroscan - info on degree of fibrosis
Ascitic tap - check for SBP or cancerous cells
Liver biopsy - gold standard for definitive diagnosis
117
what can cause the decompensation of cirrhosis?
Anything that puts extra strain on the liver has potential to cause decompensation of chronic liver disease, including:
• Dehydration
• Constipation
• Alcohol binge
• Sepsis (patients with ascites are prone to spontaneous bacterial peritonitis but may not always present with obvious symptoms)
• Excessive use of opioids
• GI bleed (leads to extra protein in the bowel, which bacteria turn into ammonia, which the liver metabolises)
118
Prescribing considerations in cirrhosis
- Warfarin – effects are enhanced, and clotting may already be deranged => bigger risk of bleeding
- Sedatives and opioids may precipitate encephalopathy
- NSAIDs and steroids can make fluid retention worse
- Hepatotoxic drugs to avoid include: paracetamol, methotrexate, isoniazid, azathioprine, aspirin etc.
119
What is the hepatopancreatic Duct/Ampulla of Vater ?
formed by the joining of the pancreatic duct and common bile duct.
120
What is the sphincter of oddi?
prevents the reflux of duodenal contents into the biliary tree and is located between the ampulla of Vater and the wall of the 2nd part of the duodenum
121
What does bile contain?
water, cholesterol, bile pigments and phosopholipids
122
Process of release of bile
1. Produced by the liver
2. Stored and concentrated in the gallbladder
3. Lipid rich food in the duodenum stimulates CCK release
4. CCK causes the gallbladder to contract and the sphincter of Oddi to relax.
5. Bile passes from the GB into the duodenum.
123
Cholelithiasis
= stones in the gallbladder.
124
Choledocholithiasis
= stones in the bile duct.
125
Cholestasis
= reduction/stoppage of bile flow
126
Which 3 factors predispose to gallstone formation?
1. Cholesterol Supersaturation
2. Stasis of Bile
3. Increased Hb breakdown - Haemolytic disorders
127
What can cause cholesterol supersaturation?
Caused by increased plasma oestrogen (obesity, pregnancy, OCP, female) and depletion of the bile acid pool (terminal ileal resection/disease)
Blood cholesterol levels have very little influence on bile cholesterol
128
What can cause stasis of bile (apart from obstruction)?
Lack of stimulus to gallbladder emptying – fasting, TPN
129
Prevalence of gallstones
Very common – prevalence of 10%.
Only 1-4% of individuals with gallstones will develop symptoms.
130
Cholesterol gallstones
~20% of gallstones
Generally caused by cholesterol supersaturation and bile stasis.
Often solitary, Large (>2.5cm), Smooth
131
Mixed gallstones
(predominantly cholesterol)
~75% of gallstones
Multiple stones
“Generations” – a range of colours and shapes
132
Bile pigment gallstones
~5% of gallstones
Multiple, Small
Black/brown colour
Irregular and fragile
133
What is the imaging modality of choice for gallstones?
USS
only ~10% of gallstones are radiopaque so most won't show up on AXR.
134
Biliary colic - pathophysiology
Stone impacted in neck of GB (Hartmann’s pouch) or cystic duct.
135
What is Hartmann's pouch?
the neck of the gallbladder
136
Biliary colic - pain/symptoms
Sudden, sharp, stabbing RUQ-epigastric pain.
Typically radiates to right shoulder
Usually lasts <6 hours.
Pain may be precipitated by eating (especially fatty foods)
May have associated N+V
137
Biliary colic - on examination/investigations
Typically unremarkable.
Apyrexial
Presence of stones on USS
138
Biliary colic - management
```
Analgesia
Outpatient cholecystectomy (within 6 weeks)
```
139
Why is biliary "colic" not a proper colic?
Biliary “colic” involves contraction of smooth muscle, but the pain is more constant than the “on and off” pain of ureteric colic and intestinal colic.
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What is Cholecystitis ?
= inflammation/infection of the gallbladder
141
Cholecystitis - pathophysiology
Stone impacted in neck of GB or cystic duct results in super concentrate, irritant bile +/- infection via ascending gut bacteria (Klebsiella, E. coli)
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Cholecystitis - pain/symptoms
Constant RUQ-epigastric pain which persists.
Radiates to right shoulder
May have N+V
Likely to have fever and/or lethargy
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Why can gallbladder pain radiate to the shoulder?
Pain radiating to the shoulder is caused by the inflamed GB irritating the liver capsule, which irritates the diaphragm above which is supplied by C3, C4, C5 (which also supplies sensation to the shoulder)
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Cholecystitis - on examination
Tender RUQ with possible guarding
| Murphy’s sign
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Cholecystitis - investigation findings
Raised inflammatory markers
Mildly deranged AST/ALT/ALP/bilirubin
USS showing enlarged gallbladder with stone(s) and thickened walls (inflammation)
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Murphy’s Sign
Whilst applying pressure in the RUQ, ask the patient to inspire deeply.
Murphy’s sign is positive when there is a halt in inspiration due to pain.
A similar manoeuvre in the LUQ should not elicit discomfort.
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specificity of Murphy's sign
Murphy’s sign is specific (if found, it is likely that the diagnosis is cholecystitis)
BUT it is not sensitive (not everyone with cholecystitis will have a positive Murphy’s sign).
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what is Cholangitis?
= inflammation/infection of the biliary system
149
Cholangitis - pathophysiology
Common Bile duct outflow obstruction and ascending infection
150
Cholangitis - pain/symptoms
RUQ pain, persistent, may be colicky in nature
Patient is jaundiced, typically unwell and pyrexial with rigors
May also have pruritis, pale stool and dark urine
Often causes sepsis
151
Cholangitis - on examination
Tender RUQ with possible guarding
| Pyrexial, jaundiced
152
Cholangitis - investigation findings
Raised WBCs, blood cultures
Raised bilirubin
Raised ALP/GGT > AST/ALT
USS will show dilated bile ducts +/- GB stones +/- duct stones
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What investigations should be done in ?gallbladder disease?
BEDSIDE:
Observations
Abdominal Exam
Urinalysis +/- pregnancy test
BLOODS:
FBC, U&E, LFT, CRP, amylase
VBG + blood cultures in cholangitis
IMAGING:
Abdominal USS
CT
MRCP/ERCP
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What are you looking for on abdominal USS in ?gallbladder disease
Presence of gallstones or sludge (start of gallstone formation)
Gallbladder wall thickness – thick walls suggest inflammation
Bile duct dilatation >6mm – possible stone/stricture
Pericholecystic fluid – local oedema
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MRCP
= Magnetic Resonance Cholangiopancreatography
Gives detailed information about the biliary tract anatomy of the patient.
Can detect stones.
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ERCP
= Endoscopic retrograde cholangiopancreatography
Gold standard for cholangitis – both diagnostic and therapeutic.
Endoscope is passed via oesophagus into duodenum, fine catheter is passed into the common bile duct.
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Gallstone Ileus
Inflammation of the gallbladder can cause a fistula between the gallbladder wall and the duodenum allowing gallstones to pass into the small bowel directly
If the stone impacts at the terminal ileum this results in small bowel obstruction
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What is the possible clinical presentation of liver tumours?
```
Symptoms:
• RUQ pain,
• Weight loss,
• Nausea
• Fever
• Late-stage symptoms include jaundice and other symptoms of liver failure.
```
```
Signs :
• hepatomegaly,
• irregular liver border,
• tender right upper quadrant
• ascites (late).
```
Investigations are likely to reveal deranged LFTs, particularly AST and ALT
159
What percentage of liver tumours are primaries/secondaries?
90% are metastases
10% are liver primaries – hepatocellular, rare types, cholangiocarcinoma
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Why is the liver a common site of metastasis?
| Where is the primary cancer usually?
= 2nd most common site of spread for solid tissue malignancies (after lymph nodes)
due to its rich bloody supply
Primaries are commonly in the lung, GI (pancreas, gastric, colorectal), breast and uterus
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Primary Hepatocellular Carcinoma
= malignant tumour of the hepatocytes
Quite rare in the UK, but common worldwide
can be nodular or infiltrative
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nodular vs infiltrative hepatocellular carcinoma
nodular – one or more discrete masses within the liver
infiltrative – diffuse throughout the liver
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What are common sites of secondary spread of hepatocellular carcinoma?
Bone
| Lungs
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What is the major risk factor for HCC and why?
liver cirrrhosis
repeated cycles of damage, inflammation and repair increase the risk of genetic mutations leading to cancer
165
Aside from cirrhosis, what are some other risk factors for HCC?
Chronic hepatitis B infection
Hepatitis C
ALD
Haemochromatosis
Primary biliary cirrhosis
NAFLD
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Prognosis of HCC
prognosis is generally poor
At diagnosis, serum alpha-fetoprotein (AFP) level is taken, and this generally correlates with tumour size and grade.
=> High AFP is poor prognostic factor
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What is a cholangiocarcinoma?
cancer in any part of the biliary tree, including inside the liver (intrahepatic)
a type of adenocarcinoma arising from the epithelial cells lining the bile ducts
168
Risk factors for cholangiocarcinoma
```
Primary sclerosing cholangitis
Anatomical abnormalities of the liver
Diabetes and Obesity
Parasite infection.
Chronic hepatitis infection
```
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Clinical presentation of cholangiocarcinoma
Painless Jaundice
Obstructive jaundice
Pruritus
Dark urine and pale stools
Presentation is often late as symptoms occur only after the bile duct is blocked.
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types of pancreatic cancer
normally a ductal adenocarcinoma which arises from the exocrine epithelial cells lining the ducts of the pancreas.
rarer types include - acinar cell carcinoma and cystoadenocarcinoma
171
Risk factors for pancreatic cancer
Smoking
Obesity and diabetes (though there is some debate whether diabetes is a contributary cause, or a result of, pancreatic cancer)
Alcohol
Chronic pancreatitis
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Location of pancreatic cancer
2/3rds are in the head of the pancreas
| 1/3rd are in the body and tail of the pancreas
173
Clinical presentation of pancreatic cancer in head of pancreas
Can compress common bile duct - they present late with painless obstructive jaundice
Symptoms include pruritus, pale stools, and dark urine
Stasis of bile can lead to infection (cholangitis) causing abdominal pain and fever
In late stages: ascites, anaemia, fatigue, nausea
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Clinical presentation of pancreatic cancer in body/tail of pancreas
General vague symptoms such as fatigue, weight loss, and nausea.
Ascites is a late feature.
May present with epigastric pain, “boring” and incessant in nature, relieved by sitting forwards. This is caused by local invasion of the coeliac plexus.
Usually very advanced at time of diagnosis
175
Complications of pancreatic cancer
New onset diabetes - Type 3c diabetes
Pancreatic exocrine insufficiency
=> Impaired production of pancreatic digestive enzymes causes steatorrhoea and malnutrition.
Venous thrombo-embolism (DVT or PE)
=> Common to most cancers as there is a hypercoagulable state
