Cirrhosis & its Consequences Flashcards
1
Q
What is cirrhosis?
What is the end result of this process?
A
it is a diffuse process that results from liver cell necrosis** followed by **fibrosis** and **nodule formation
the end result is impairment of liver cell function and gross distortion of the liver architecture, leading to portal hypertension
2
Q
What is the most common cause of cirrhosis?
A
- alcohol is the most common cause in the western world
- viral hepatitis is the most common cause worldwide
3
Q
What are the 3 most common causes of cirrhosis and what are non-invasive markers of aetiology?
A
Alcohol:
- history of excess alcohol consumption
Chronic hepatitis B:
- HBsAg +/- HBeAg/DNA in serum
Chronic hepatitis C:
- HCV antibodies and HCV RNA in serum
4
Q
What are 4 other conditions that are commonly seen in clinical practice that can cause cirrhosis?
What are non-invasive markers of aetiology?
A
Haemochromatosis:
- family history
- raised serum ferritin + transferrin saturation
Non-alcoholic fatty liver disease:
- features of the metabolic syndrome
- hyperechoic liver on ultrasound
Primary biliary cirrhosis:
- presence of serum antimitochondrial antibodies
Sclerosing cholangitis (primary & secondary):
- most patients have IBD and serum pANCA
- multifocal stricturing and dilatation of bile ducts on cholangiography (MRCP or ERCP)
5
Q
What are non-invasive markers of aetiology for autoimmune hepatitis and cystic fibrosis, which can cause cirrhosis?
A
Autoimmune hepatitis:
- circulating autoantibodies
- hypergammaglobulinaemia
Cystic fibrosis:
- presence of extrahepatic manifestations of CF
6
Q
What non-invasive markers of aetiology are present in Budd-Chiari syndrome, causing cirrhosis?
A
- presence of known risk factors
- caudate lobe hypertrophy
- abnormal flow in major hepatic veins on USS
7
Q
What non-invasive markers of aetiology are present in Wilson’s disease, leading to cirrhosis?
A
- young age
- reduced serum caeruloplasmin and total copper
- increased 24-hour urinary copper excretion
- Kayser-Fleisher rings
8
Q
What are non-invasive markers of aetiology in a1-antitrypsin (AAT) deficiency, leading to cirrhosis?
A
- young age
- associated emphysema
- reduced serum AAT
9
Q
What are the 2 different types of cirrhosis histologically?
A
- micronodular cirrhosis
- macronodular cirrhosis
- there is a mixed picture, with both small and large nodules
10
Q
What is micronodular cirrhosis and when is this often seen?
A
- characterised by uniform, small nodules up to 3mm in diameter
- this is often caused by alcohol damage
11
Q
What is macronodular cirrhosis and what is this associated with?
A
- this involves large nodules that are up to several centimetres in diameter
- this often occurs following hepatitis B infection
12
Q
What are the clinical features of cirrhosis a result of?
A
clinical features are secondary to portal hypertension and liver cell failure
13
Q
What is the difference between compensated and uncompensated cirrhosis?
A
Uncompensated cirrhosis:
- cirrhosis with the complications of encephalopathy, ascites or variceal haemorrhage
Compensated cirrhosis:
- cirrhosis without any of these complications
14
Q
Why are investigations carried out in cirrhosis?
A
- to assess the severity of the liver disease
- to identify the aetiology
- to screen for complications
15
Q
What do liver biochemistry and liver function tests usually show in cirrhosis?
A
Liver biochemistry:
- may be normal
- in most people there is at least a slight elevation in serum alkaline phosphatase (ALP) and aminotransferase
Liver function:
- serum albumin is reduced
- prothrombin time is prolonged
- these reflect reduced hepatic synthesis
16
Q
What will serum electrolytes show in cirrhosis?
A
- low sodium concentration indicates severe liver disease secondary to either impaired free water clearance or excess diuretic therapy
17
Q
What is serum a-fetoprotein (AFP) and why is this test performed?
A
- usually undetectable after foetal life, but raised levels may occur in chronic liver disease
- measured to screen for complications of hepatocellular carcinoma (HCC)
- normal range is 10-20 ng/mL
- a level > 400 ng/mL is regarded as diagnostic of HCC
18
Q
How is the aetiology of cirrhosis confirmed?
A
the cause is determined by the history combined with laboratory investigations
a liver biopsy is performed to confirm the severity and type of liver disease
19
Q
What further investigations may be carried out in cirrhosis?
A
- oesophageal varices are sought with endoscopy
- USS is useful for detection of hepatocellular carcinoma (HCC)
- USS is used to assess the patency of the portal and hepatic veins
20
Q
A
21
Q
What is involved in the management of cirrhosis?
How are the underlying causes commonly corrected?
A
- cirrhosis is irreversible, so treatment is aimed at treating the complications seen in decompensated cirrhosis as they arise
- venesection is used to correct haemochromatosis
- abstinence from alcohol is used to correct alcoholic hepatitis
- correcting the underlying cause may halt the progression of liver disease
22
Q
What 5 variables are used to grade the severity and prognosis of liver disease?
What is 5-year survival like?
A
- encephalopathy
- ascites
- prothrombin time
- serum bilirubin
- serum albumin
- overall the 5-year survival rate without transplantation is 50%
23
Q
What are the 7 most common complications of cirrhosis?
A
- portal hypertension and variceal haemorrhage
-
ascites
- this can become infected ascites (spontaneous bacterial peritonitis)
- portosystemic encephalopathy
- acute renal failure (hepatorenal syndrome)
- hepatocellular carcinoma (HCC)
- malnutrition
- osteoporosis
24
Q
What is the role of the portal vein?
A
- it carries blood from the gut and the spleen to the liver
- it accounts for 75% of hepatic vascular inflow
- the other 25% comes from the hepatic artery
25
How does blood enter and leave the liver?
* blood enters the liver via the **_hepatic artery_** and the **_portal vein_**
* these blood vessels enter the liver via the **hilum (porta hepatis)**
* blood passes into the **_hepatic sinusoids_** via the **portal tracts**
* blood leaves the liver via the **_hepatic veins_**, which join the **_inferior vena cava_**
* the vena cava returns blood to the right side of the heart
26
What is normal portal pressure?
What happens in portal hypertension?
* normal portal pressure is **_8 - 10 mmHg_**
* portal hypertension occurs when there is an **increase in pressure** within the **_portal vein_** and **its branches**
* these are draining blood from the intestines, stomach, pancreas etc. to the liver
27
What happens when the inflow of portal blood to the liver is obstructed?
What site is the most significant for collateral formation?
* the inflow of portal blood to the liver can be **partially** or **completely obstructed** at a number of sites
* this leads to **high blood pressure _proximal_ to the obstruction** and the **diversion of blood into _portosystemic collaterals_**
* the most important site for collateral formation is at the **_gastro-oesophageal junction_** (varices)
* here the collaterals are superficial and **liable to rupture**, causing **massive gastrointestinal haemorrhage**
28
What are the 3 main sites of obstruction to the inflow of portal blood to the liver?
***_Prehepatic:_***
* obstruction of the **_portal vein_** before it reaches the liver
***_Intrahepatic:_***
* this results from distortion of the **_liver architecture_**
***_Posthepatic:_***
* this results from obstruction of the **_hepatic veins_**
29
What is the main prehepatic cause of portal hypertension?
**portal vein thrombosis**
30
What are the main causes of intrahepatic portal hypertension?
* cirrhosis
* alcoholic hepatitis
* idiopathic non-cirrhotic portal hypertension
* schistosomiasis
31
What are the post-hepatic causes of portal hypertension?
* Budd-Chiari syndrome
* veno-occlusive disease
* right heart failure (this is rare)
* constrictive pericarditis
32
What are the 3 characteristic clinical manifestations of portal hypertension?
* **gastrointestinal bleeding** from oesophageal or gastric (less common) varices
* **ascites**
* **hepatic encephalopathy**
33
How common is variceal haemorrhage?
What is the mortality like?
* **30%** of patients with varices will actually bleed from them
* bleeding is most common in patients with **large varices**
* bleeding is often **massive** with **high mortality of 50%**
34
What is the management of acute bleeding from variceal haemorrhage?
patients should be resuscitated and undergo **urgent gastroscopy** to **confirm the diagnosis** and exclude bleeding from other sites
**endoscopic therapy** is the treatment of choice for active variceal haemorrhage
35
What are the 2 forms of endoscopic treatment to stop bleeding from oesophageal varices?
***_Sclerotherapy:_***
* this involves injection of a **sclerosant solution** (e.g. ethanolamine) into the varices
***_Variceal band ligation:_***
* similar to haemorrhoidal banding and involves placing **small elastic bands** around the varices
36
When is pharmacological treatment used for the treatment of oesophageal varices?
* this is used for emergency control of bleeding whilst **waiting for endoscopy** and **in combination** with endoscopic techniques
* this usually involves **_terlipressin_** or **_octreotide_**
37
What does terlipressin do?
What dose is given and when is it contraindicated?
* terlipressin is a synthetic analogue of **_vasopressin_**
* it **restricts portal inflow** by **_splanchnic arterial constriction_**
* it is given by **intravenous bolus injection** - **_2mg every 6 hourly_**
* it is contraindicated in patients with **ischaemic heart disease**
38
What is octreotide and how does it work?
What dose should be given?
* it is a **somatostatin analogue**
* it **_lowers portal pressure_** by a similar mechanism to terlipressin but it is **less effective**
* **50ug IV stat** is given followed by **50ug hourly** by **intravenous infusion**
39
What is used to treat acute bleeding from oesophageal varices if endoscopy and pharmacological treatment don't work?
What are the risks associated with this and how are they managed?
* **_balloon tamponade_** with a **_Sengstaken-Blakemore tube_** is used if bleeding continues
* It can have **serious complications**, such as:
* aspiration pneumonia
* oesophageal rupture
* mucosal ulceration
* to reduce complications the airway should be **protected** and the tube left in situ for **no longer than 12 hours**
40
What method is used if there is a second rebleed after treatment for variceal haemorrhage?
What does this involve?
**_transjugular intrahepatic portosystemic shunting (TIPS)_**
* a metal stent is passed over a guidewire in the **internal jugular vein**
* the stent is pushed into the **liver substance**, under radiological guidance, to form a **shunt between the _portal and hepatic veins_**
* this **_lowers portal pressure_**
41
What additional antibiotics and medication are given to cirrhosis patients following treatment for variceal haemorrhage?
* **bacterial infection** is common after upper GI bleeding in cirrhosis patients
all patient should have **antibiotic prophylaxis** with **_ciprofloxacin_**
this is **_500mg twice daily_** for **_7 days_**
* **_lactulose_** should be given to prevent **portosystemic encephalopathy**
* **_sucralfate_** should be given to reduce **oesophageal ulceration**, which is a complication of endoscopic therapy
42
What type of prophylaxis is given after an episode of variceal bleeding and why?
* there is a **high risk of recurrence** (60-80% over a 2-year period)
* treatment is given to **prevent further bleeds**
* this is **_secondary prophylaxis_**
43
What drug is given as secondary prophylaxis for variceal bleeding?
**_oral propanolol_**
* this **decreases portal pressure**
* some patients are intolerant of treatment due to **side effects**
* it is also given as **primary prophylaxis** for patients who have **never bled**
44
If oral propanolol does not work or is not tolerated, what secondary prophylaxis may be given for variceal bleeding?
* repeated courses of **_variceal banding_** at **2-weekly intervals** until the varices are obliterated
* **TIPS** or a surgical **_portosystemic shunt_** (portal vein to vena cava)
this is done if endoscopic or medical therapy fails
45
What is ascites?
it is the presence of **_fluid_** in the **_peritoneal cavity_**
it is a common complication of **cirrhosis** of the liver
46
Why does ascites occur?
* in cirrhosis, there is **peripheral arterial vasodilation** that is mediated by vasodilators including **nitric oxide**
* this leads to a **reduction in _effective blood volume_**
* there is activation of the **renin-angiotensin system**
* this promotes renal **_salt and water retention_**
* the formation of **oedema** is encouraged by **_hypoalbuminaemia_** and is localised to the peritoneal cavity as a result of **_portal hypertension_**
* increased pressure can force fluid into the abdominal cavity
47
What are the clinical features of ascites?
* there is **fullness in the flanks**, with **_shifting dullness_**
* **tense** ascites is **uncomfortable** and may produce **respiratory distress**
* a **_pleural effusion_** (usually **right-sided**) and **_peripheral oedema_** may be present
48
What investigations are carried out when ascites is present?
a **diagnostic aspiration** (**_paracentesis_**) of **_10-20ml_** of fluid is carried out in all patients and the following performed:
* **cell count**
* **Gram stain and culture** for bacteria and acid-fast bacilli
* **protein**
* **cytology** for malignant cells
* **amylase** to exclude pancreatic ascites
49
Why is a cell count performed in patients with ascites?
a **neutrophil count \> 250 cells / mm3** indicates underlying (usually spontaneous) **_bacterial peritonitis_**
50
Why is ascitic fluid tested for protein?
* an ascitic protein level of **11 g/L or more below the serum albumin level** suggests a **_transudate_**
* a ascitic protein level of **\< 11 g/L below the serum albumin level** suggests an **_exudate_**
51
What is the difference between a transudate and an exudate?
***_Transudate:_***
* an ultrafiltrate of plasma that contains **_very few cells_**
* it does NOT contain large plasma proteins
* results from **increased hydrostatic** or **reduced oncotic** pressure
***_Exudate:_***
* this is a sign of inflammation that contains many **_inflammatory cells_**
* a consequence of **increased vascular permeability**
52
What are the causes of transudate ascites?
* cirrhosis
* constrictive pericarditis
* cardiac failure
* hypoalbuminaemia (e.g. nephrotic syndrome)
* Meig's syndrome
* a combination of an ovarian tumour, ascites and a hydrothorax
53
What are the causes of exudate ascites?
* malignancy
* infection
* pancreatitis
* Budd-Chiari syndrome
* myxodema
* lymphatic obstruction
54
What is the first stage in the management of ascites resulting from cirrhosis (portal hypertension)?
* management is a stepwise approach
* it starts with **_dietary sodium restriction_** (60 mmol/day)
* and **oral _spironolactone_ (100mg daily)** is also given
* this is a potassium sparing diuretic
* this is increased gradually **up to 400 mg daily** if necessary
55
What medication is added if the response to spironolactone is poor in ascites caused by portal hypertension?
* **_furosemide_ 20 - 40 mg daily** is added
* this is increased up to **160 mg** if necessary
56
By how much does diuretic therapy aim to reduce fluid by daily in ascites?
How is this best measured?
* the rate of fluid loss is best assessed through **_changes in bodyweight_**
* the aim is to produce weight loss of around **_0.5kg per day_**
* this is because the maximum rate of transfer of fluid from the ascitic to the vascular compartment is only about **700 mL / day**
57
What can happen if diuresis of ascitic fluid occurs too rapidly?
* it can cause **volume depletion** and **_hypokalaemia_**
* it also precipitates **encephalopathy**
58
What treatment approach is used in patients with tense ascites or those who are resistant to standard therapy with diuretics?
**_paracentesis_**
* this involves a needle / drain being inserted into the peritoneal cavity
* all of the ascites is removed over several hours
* this provides rapid symptoms relief and reduced hospital stay compared with treatment with diuretics
59
What is the major danger associated with paracentesis to treat ascites and how is this overcome?
* the major danger of this approach is the production of **_hypovolaemia_**
* this is because the **ascites reaccumulates** at the expense of the **circulating volume**
* this is overcome by administering an **_intravenous infusion of albumin_** (**8g per litre removed**) immediately after paracentesis
60
What is the most common complication associated with ascites?
How does this tend to present?
***_spontaneous bacterial peritonitis (SBP)_***
* the most common infecting organism is ***_E. coli_***
* clinical features are minimal, but include **abdominal pain** and **fever**
61
How is spontaneous bacterial peritonitis diagnosed?
What is the treatment?
* diagnosis is made based on the **ascitic fluid _white cell count_, _Gram stain_ and _culture_**
* empirical therapy is started in all patients with an ascitic fluid **neutrophil count** **_\>/= 250 cells/mm3_** rather than waiting for the results of the culture
* this usually involves **_IV cefotaxime_ 2g every 8 hourly**
62
What antibiotic can be given for prophylaxis following SBP?
* SBP recurrence is common
* **_oral norfloxacin_** can be given for prophylaxis
63
What is portosystemic encephalopathy?
it refers to a **chronic _neuropsychiatric_ syndrome** which occurs with **advanced hepatocellular disease**
this is either **chronic** (cirrhosis) or **acute** (fulminant hepatic failure)
64
What is involved in the pathophysiology of portosystemic encephalopathy?
* the mechanisms are unknown but are believed to involve **_"toxic" substances_**, normally detoxified by the liver, **bypassing the liver via the collaterals** and gaining access to the **_brain_**
* a putative toxin is **_ammonia_**, produced from the breakdown of **dietary protein** by gut bacteria
65
What are the early and later clinical features of portosystemic encephalopathy?
***_Earliest features:_***
* lethargy
* mild confusion
* anorexia
* reversal of the sleep pattern
* the patient sleeps during the day and is restless at night
***_Later features:_***
* disorientation
* decreased conscious level
* eventually this leads to **coma**
66
What are the 4 main clinical features associated with portosystemic encephalopathy?
* **_fetor hepaticus_** - this is a **sweet smell** to the breath
* **_asterixis_** - **flapping tremor** of the outstretched hand
* **_constructional apraxia_** - the inability to draw a **five-pointed star**
* **_prolonged trail-making test_** - the ability to join numbers and letters within a certain time
67
What investigations are involved in portosystemic encephalopathy?
* the diagnosis is **_clinical_**
* an **EEG** showing **delta waves** and visual **evoked potentials** may aid diagnosis in difficult cases
68
What are the factors known to precipitate portosystemic encephalopathy?
* **gastrointestinal haemorrhage** (i.e. a high protein load)
* **infection**
* **fluid** and **electrolyte disturbance** (spontaneous or diuretic induced)
* **sedative drugs**
* e.g. opiates, diazepam
* development of a **hepatoma** (HCC)
* portosystemic shunt operations and TIPS
* **constipation**
* **high dietary protein**
69
What are the aims of management for portosystemic encephalopathy?
the aims of management are to identify and treat any **precipitating factors**
and to **minimize the absorption of _nitrogenous material_**, particularly **_ammonia_**, from the gut
70
What is the main medication given for the treatment of portosystemic encephalopathy?
***_laxatives_***
* **_oral lactulose_** (10 - 30 ml three times daily)
* this is an **osmotic purgative** that **reduces colonic pH** and **increases transit**
* it is given via a nasogastric tube if the patient is comatose
* the dose should be titrated to result in **2-4 soft stools daily**
71
What antibiotics are given in the management of portosystemic encephalopathy and why?
* antibiotics are given to **reduce the number of bowel organisms** and hence production of **_ammonia_**
* **_rifaximin_** is mainly unabsorbed and well tolerated
* **_oral metronidazole_** (200 mg four times daily) is also used
72
What supportive treatment is given in portosystemic encephalopathy?
**maintenance of nutrition** with **adequate calories**
protein is initially restricted but increased after 48 hours as encephalopathy improves
73
What is hepatorenal syndrome?
this is the development of **_acute renal failure_** in a patient who usually has **_advanced liver disease_**
this is either **cirrhosis** or **alcoholic hepatitis**
74
Why does hepatorenal syndrome occur?
* **_splanchnic vasodilation_** (vessels that supply the intestines) results in a fall in **systemic vascular resistance**
* and **severe vasoconstriction of the renal circulation** with markedly **_reduced renal perfusion_**
75
How is hepatorenal syndrome diagnosed?
* **oliguria**
* a **rising serum creatinine** (over days to weeks)
* a **low urine sodium** (\<10 mmol/L)
* absence of **other causes** of renal failure
* lack of improvement after **volume expansion** (if needed) and **withdrawal of diuretics**
76
What is the prognosis like in hepatorenal syndrome and what treatments are available?
* the prognosis is **poor** and renal failure will often only respond to an improvement in liver function
* **_albumin infusion_** and **_terlipressin_** have been used with some success
