The portal vein is formed by the union of superior mesenteric (from the gut) and splenic vein (from the spleen) and carries blood to the liver.
|Table 4.7 Complications and effects of cirrhosis|
Portal hypertension and gastrointestinal haemorrhage Ascites
Liver, biliary tract and pancreatic disease
Acute kidney injury (hepatorenal syndrome)
Table 4.8 Causes of portal hypertension
Portal vein thrombosis
diopathic non-cirrhotic portal hypertension
Right heart failure (rare)
nferior vena caval obstruction
It accounts for 75% of hepatic vascular inflow; 25% is via the hepatic artery. Blood vessels enter the liver via the hilum (porta hepatis) and blood passes into the hepatic sinusoids via the portal tracts and leaves the liver through the hepatic veins to join the inferior vena cava. The normal portal pressure is 5-8 mmHg. The inflow of portal blood to the liver can be partially or completely obstructed at a number of sites, leading to high pressure proximal to the obstruction and the diversion of blood into portosystemic collaterals, e.g. at the gastro-oesophageal junction (varices), where they are superficial and liable to rupture, causing massive gastrointestinal haemorrhage.
The main sites of obstruction are:
■ Prehepatic, due to blockage of the portal vein before the liver
■ Intrahepatic, resulting from distortion of the liver architecture
■ Posthepatic, due to venous blockage outside of the liver (rare).
The most common cause (Table 4.8) of portal hypertension is cirrhosis.
164 Liver, biliary tract and pancreatic disease
The only evidence of portal hypertension may be splenomegaly in a patient with clinical signs of chronic liver disease. The common presenting features are:
■ Gastrointestinal bleeding from oesophageal or less commonly gastric varices
■ Hepatic encephalopathy.
Most patients with cirrhosis will eventually develop varices but only a third will bleed from them. Bleeding is often massive and mortality is as high as 50%.
The general management of gastrointestinal bleeding is discussed on page 87 and the management of varices is summarized in Fig. 4.7.
Active bleeding Patients should be resuscitated and undergo urgent gastroscopy to confirm the diagnosis and exclude bleeding from other sites.
Fig. 4.7 Management of gastrointestinal haemorrhage due to oesophageal varices. TIPS, transjugular intrahepatic portosystemic shunt.
■ Endoscopic therapy is the treatment of choice and will stop bleeding in 80% of cases bleeding from oesophageal varices. The common endo-scopic methods are band ligation (small elastic bands are placed over the varices) or sclerotherapy (injection of a sclerosant solution, e.g. ethanolamine, into the varices).
■ Pharmacological treatment is used for emergency control of bleeding while waiting for endoscopy and in combination with endoscopic techniques. Terlipressin (a synthetic analogue of vasopressin) restricts portal inflow by splanchnic arterial constriction. It is given by intravenous bolus injection (2 mg 6-hourly) and is contraindicated in patients with ischaemic heart disease. Somatostatin, an intravenous infusion of 250500 μg/h lowers portal pressure by a similar mechanism to terlipressin but is less effective. It is used when there are contraindications to terlipressin.
■ Balloon tamponade with a Sengstaken-Blakemore tube is used if medical or endoscopic treatment described above has failed or contraindicated, or if there is exsanguinating haemorrhage. The gastric balloon is inflated and pulled back against the gastro-oesophageal junction to prevent cephalad variceal blood flow to the bleeding point. It can have serious complications, such as aspiration pneumonia, oesophageal rupture and mucosal ulceration. To reduce complications, the airway should be pro-tected, and the tube left in situ for no longer than 12 hours. It is removed immediately prior to endoscopy.
■ TIPS (transjugular intrahepatic portosystemic shunting) is used when there is a second rebleed after treatment. A metal stent is passed over a guidewire in the internal jugular vein. The stent is then pushed into the liver substance, under radiological guidance, to form a shunt between the portal and hepatic veins, thus lowering portal pressure.
■ Surgery (oesophageal transection and ligation of varices) is occasionally necessary if bleeding continues in spite of all the above measures.
■ Additional treatment. Patients require high-dependency/ intensive care unit nursing. Antibiotic prophylaxis, e.g. cefotaxime, is given to prevent infection, and reduce rebleeding and early mortality. Lactulose is given to prevent portosystemic encephalopathy, and sucralfate to reduce oesophageal ulceration, a complication of endoscopic therapy.
Prevention of recurrent variceal bleeding
Following an episode of variceal bleeding there is a high risk of recurrence (60-80% over a 2-year period), and treatment is given to prevent further bleeds (secondary prophylaxis). The main options are:
■ Oral propranolol (in a dose sufficient to reduce the resting pulse rate by 25%) lowers portal pressure, but some patients are intolerant of treat-ment because of side-effects. Propranolol is also given to patients with varices who have never bled (primary prophylaxiẩ).
■ Repeated courses of variceal banding at 2-weekly intervals until the varices are obliterated. Varices may recur so follow-up endoscopy is required.
■ TIPS or occasionally a surgical portosystemic shunt is performed if endo-scopic or medical therapy fails. Hepatic encephalopathy is a complication of both procedures. Liver transplantation should always be considered when there is poor liver function.
This is the presence of fluid in the peritoneal cavity. Cirrhosis is the com-monest cause (Table 4.9).
In cirrhosis, peripheral arterial vasodilatation (mediated by nitric oxide and other vasodilators) leads to a reduction in effective blood volume, with activa-tion of the sympathetic nervous system and renin-angiotensin system, thus promoting renal salt and water retention. The formation of oedema is encour-aged by hypoalbuminaemia and mainly localized to the peritoneal cavity as a result of the portal hypertension.
There is fullness in the flanks, with shifting dullness. Tense ascites is uncom-fortable and produces respiratory distress. A pleural effusion (usually right-sided) and peripheral oedema may be present.
A diagnostic aspiration of 10-20 mL of ascitic fluid should be carried out in all patients, and the following performed:
Table 4.9 Causes of ascites
Portal hypertension, e.g. cirrhosis
Hepatic outflow obstruction
Hepatic veno-occlusive disease
Lymphatic obstruction (chylous ascites)
*Meig s syndrome is the triad of benign ovarian íibroma, ascites and pỉeuraỉ effusion.
■ Albumin. An ascitic albumin concentration of 11 g/L or more below the serum albumin suggests a transudate; a value of <11 g/L suggests an exudate (Table 4.9).
■ A neutrophil count >250 cells/mm3 in cirrhotic ascites indicates under-lying (usually spontaneous) bacterial peritonitis.
■ Gram stain and culture for bacteria and acid-fast bacilli.
■ Cytology for malignant cells.
■ Amylase to exclude pancreatic ascites.
Treatment depends on the cause. The management of ascites due to portal hypertension is described below. In other cases, ascites will improve with treatment of the underlying condition.
Diuretics The management of ascites resulting from cirrhosis is based on a step-wise approach, starting with dietary sodium restriction (40 mmol/ day) and oral spironolactone 100 mg daily, increasing gradually to 500 mg daily if necessary. Furosemide (frusemide) 20-40 mg daily is added if the response is poor. The aim of treatment is to lose about 0.5 kg of body weight each day because the maximum rate of transfer of fluid from the ascitic to the vascular compartment is only about 700 mL/day. Too rapid a diuresis causes intravascular volume depletion and hypokalaemia, and precipitates encephalopathy. Efficacy and side effects of treatment is monitored by body weight and serum creatinine and sodium. A rising creatinine level or hyponat-raemia indicates inadequate renal perfusion and the need for temporary cessation of diuretic therapy (if sodium <128 mmol/L). This approach to treating ascites is effective in over 90% of patients.
Paracentesis is used in patients with tense ascites or who are resistant to standard medical therapy. All the ascites can be removed over several hours providing rapid symptom relief. Intravenous infusion of albumin (8 g/L removed) administered immediately after paracentesis increases the circulat-ing volume (ascites reaccumulates at the expense of the circulating volume).
Transjugular intrahepatic portosystemic shunt (TIPS, p. 165) is occa-sionally used for resistant ascites.
Spontaneous bacterial peritonitis (SBP) occurs in 8% of cirrhotic patients with ascites and has a mortality rate of 10-15%. The most common infecting organism is Escherichia coli. Clinical features may be minimal and the diagnosis should be suspected in any patient with cirrhotic ascites who deteriorates. Diagnostic aspiration should always be performed and empirical antibiotic therapy with a third generation cephalosporin, e.g. intra-venous cefotaxime, is started if the ascitic fluid neutrophil count >250 cells/ mm3. Antibiotics can subsequently be adjusted on the basis of culture results. Antibiotic prophylaxis with oral norfloxacin is indicated in patients after one episode or in patients at high risk (ascites protein <10 g/dL or severe liver disease). SBP is also an indication for referral to a liver transplant centre.
Portosystemic encephalopathy (PSE) is a neuropsychiatric syndrome which occurs with advanced hepatocellular disease, either chronic (cirrhosis) or acute (fulminant hepatic failure). It is also seen in patients following surgical or TIPS shunts.
The mechanisms are unclear but are believed to involve ‘toxic' substances, normally detoxified by the liver, bypassing the liver via the collaterals and gaining access to the brain. Ammonia plays a major role and is produced from breakdown of dietary protein by gut bacteria. In chronic liver disease there is an acute-on-chronic course, with acute episodes precipitated by a number of possible factors (Table 4.10).
An acute onset often has a precipitating cause; the patient becomes increas-ingly drowsy and eventually comatose (Table 4.5). There is increased tone and hyperreflexia. Chronically, the patient may be irritable, confused, with slow, slurred speech and a reversal of the sleep pattern, with the patient sleeping during the day and restless at night. The signs are fetor hepaticus (a sweet smell to the breath), a flapping tremor of the outstretched hand (asterixis), inability to draw a five-pointed star (constructional apraxia) and a prolonged trail-making test (the ability to join numbers and letters within a certain time). Serial attempts are easily compared and used to monitor patient progress.
None of the manifestations of hepatic encephalopathy are specific to this disorder. Alternative diagnoses such as other metabolic or toxic
|Table 4.10 Factors precipitating portosystemic encephalopathy|
|High dietary protein
Gastrointestinal haemorrhage (i.e. a high protein load)
Infection including spontaneous bacterial peritonitis
Fluid and electrolyte disturbance (spontaneous or diuretic-induced)
Sedative drugs, e.g. opiates, diazepam
Portosystemic shunt operations and TIPS
Any surgical procedure
Progressive liver damage
Development of hepatocellular carcinoma
|TIPS, transjugular intrahepatic poitocaval shunt.|
encephalopathies or intracranial mass lesions may present similarly and should be considered.
Liver, biliary tract and pancreatic disease
The diagnosis is clinical. An electroencephalogram (EEG) (showing s waves), visual evoked potentials and arterial blood ammonia are sometimes used in difficult diagnostic cases or to follow patients (ammonia).
The aims of management are to identify and treat any precipitating factors (Table 4.10) and to minimize the absorption of nitrogenous material, particu-larly ammonia, from the gut. This is achieved by the following:
■ Laxatives. Oral lactulose (10-30 mL three times daily) is an osmotic purgative that reduces colonic pH and limits ammonia absorption. It may be given via a nasogastric tube if the patient is comatose. The dose should be titrated to result in 2-4 soft stools daily.
■ Antibiotics are given to reduce the number of bowel organisms and hence production of ammonia. Rifaximin is mainly unabsorbed and well toler-ated. Oral metronidazole (200 mg four times daily) is also used.
■ Maintenance of nutrition with adequate calories. Protein is initially restricted but increased after 48 hours as encephalopathy improves.
The prognosis is that of the underlying liver disease.
This is the development of acute kidney injury in a patient who usually has advanced liver disease, either cirrhosis or alcoholic hepatitis. Marked periph-eral vasodilatation leads to a fall in systemic vascular resistance and effective hypovolaemia. This in turn results in vasoconstriction of the renal circulation with markedly reduced renal perfusion. The diagnosis is made on the basis of oliguria, a rising serum creatinine (over days to weeks), a low urine sodium (<10 mmol/L), absence of other causes of acute kidney injury, and lack of improvement after volume expansion (if necessary) and withdrawal of diu-retics. 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.
Intrapulmonary vascular dilatation in patients with advanced liver disease causes hypoxaemia. In severe disease patients are breathless on standing.
Diagnosis is by echocardiogram and the changes improve with liver transplantation.
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER DISEASE IN PREGNANCY
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS
5. Haematological disease
Assessment and treatment of suspected neutropenic sepsis
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
6. Malignant disease
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
8. Water, electrolytes and acid–base balance
WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
9. Renal disease
INVESTIGATION OF RENAL DISEASE
URINARY TRACT INFECTION
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
10. Cardiovascular disease
COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
ISCHAEMIC HEART DISEASE
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
ARTERIAL AND VENOUS DISEASE
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS
11. Respiratory disease
12. Intensive care medicine
13. Drug therapy, poisoning, and alcohol misuse
14. Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
15. Diabetes mellitus and other disorders of metabolism
16. The special senses
COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES