Liver and friends Flashcards
Liver failure definition
Hepatic failure occurs when the liver loses the ability to regenerate or repair, so that decompensation occurs. It is characterised by:
- hepatic encephalopathy
- abnormal bleeding
- ascites
- jaundice
Liver failure epidemiology
Globally, viral infection accounts for the majority of cases of liver failure, however, paracetamol overdose is the leading cause in the UK.
Liver failure aetiology
Toxins - chronic alcohol abuse, paracetamol poisoning
Infections - viral heapatitis, adenovirus, epstin-barr virus
Neoplastic - hepatocellular carcinoma or metastatic carcinoma
Metabolic - Wilson’s disease, alpha-1-antitrypsin deficiency
Pregnancy-related - acute fatty liver of pregnancy
Vascular - ischaemia or veno-occlusive disease, Budd-Chiari syndrome
Others - autoimmune liver disease (PBC, PSC), unknown cause - 15%
Liver failure pathophysiology
Dependent on cause
Liver failure signs and symptoms
Mental state showing dowsiness and possibly confusion
Jaundice
Abdominal distention and abdominal masses including:
- possible massive ascites and anasarca (general swelling) due to fluid distribution and hypoalbuminemia
- hepatomegaly and splenomegaly
Cerebral oedema with increased ICP may produce papilloedema (optic disc swelling, seen on fundoscopy)
Liver palms (palmar erythema [reddening of the thenar and hypothenar eminences])
Asterixis (tremor on wrist extension)
Signs of hepatic encephalopathy
Liver failure 1st line investigations
Bloods:
- likely to see iron-deficient anaemia
- may show thrombocytopenia (low platelets)
- raised INR
- markedly raised transaminases (AST and ALT) but alkaline phosphate may be high or normal
- raised bilirubin
- high ammonia
- glucose can be dangerously low
- blood cultures - patients are very susceptible to infection
Imaging:
- doppler ultrasound - look for patents hepatic vein, carcinoma and ascites
- imaging of the head - cerebral oedema
Liver failure management
Conservative: fluids and analgesia
Possibility of liver transplantation should be considered at an early stage
Underlying cause should be assessed and managed
Treat complications:
- ascites - diuretics
- cerebral oedema - Mannitol
- bleeding - Vitamin K
- encephalopathy - Lactulose
- sepsis - sepsis 6, antibiotics
- hypoglycaemia - dextrose
Liver failure complications
Infection is a big problem - spontaneous peritonitis is common
Cerebral oedema may be associated with intracranial hypertension and death
Haemorrhage from oesophageal varices is a major complication
Cholelithiasis (gallstones) definition
The presence of solid concretions in the gallbladder. Usually form in the gallbladder but may enter into the bile ducts (choledocholithiasis). Symptoms occur if a stone obstructs the cystic, bile or pancreatic ducts. In the developed world most gallstone are made of cholesterol.
Cholelithiasis (gallstones) aetiology
Mostly due to cholesterol composed stones forming in the gallbladder.
Around 5% of gallstone are black pigment stones. These consist of polymerised calcium bilirubinate. Patients with chronic haemolytic anaemia, cirrhosis. cystic fibrosis and ilial disease are at a higher risk of black pigment stones.
Brown pigment gallstones result from stasis and infection and form in the bile ducts. May be due to bacterial infection or biliary parasites although in the west they are more commonly from biliary stricture, either inflammatory or neoplastic.
Cholelithiasis (gallstones) risk factors
Age, female sex, overweight, oestrogen (pregnancy/exogenous)
Cholelithiasis (gallstones) pathophysiology
Symptoms and complications result when stones obstruct the cystic and/or bile ducts. Transient obstruction of the cystic duct results in biliary pain (biliary colic). More persistent obstruction leads to acute cholecystitis (inflammation of the gallbladder).
Mirizzi syndrome is an uncommon condition where a large gallstone is impacted in the cystic duct or neck of the gallbladder, compresses the common bile duct and causes obstruction and jaundice.
If gallstones pass into the bile ducts causing obstruction, the result can be biliary and acute cholangitis (inflammation of the bile duct system)
Stone passage through the distal bile duct cab culminate in obstruction at the ampulla. Acute biliary pancreatitis results from the increase in pancreatic ductal pressure and reflux of pancreacticobiliary scretions into the pancreatic duct.
If a gallstone erodes through the gallbladder wall, a cholecystoenteric fistula can develop leading to duodenal obstruction (Bouveret syndrome) or obstruction in the narrowest segment of an otherwise healthy bowel causing gallstone ileus.
Cholelithiasis (gallstones) signs and symptoms
Gallstones themselves are common and are usually asymptomatic unless causing obstruction and/or inflammation.
Right upper quadrant or epigastric pain is the most common symptom of cholelithiasis and is caused by obstruction of the cyctic duct or obstruction and/or passage of a gallstone through the common bile duct.
Biliary pain:
- radiated to the right back or shoulder
- responds to analgesia
- often occurs 1hr after food
- may have associated nausea and vomiting
- becomes increasingly intense then stabilizes
These symptoms together with fever and abdominal tenderness (Muphy’s sign: pain on palpation during inspiration) indicates the development of acute cholecystitis. A distended, tender gallbladder may be palpable in acute cholecystitis
Cholelithiasis (gallstones) 1st line investigations
Biliary colic due to a stone in the neck of the gallbladder or cystic duct is unlikely to be associated with significant abnormalities of tests. Acute cholecystitis is usually associated with moderate leukocytosis and raised inflammatory markers (eg CRP).
FBC - leukocytosis with AC
Bilirubin - may be raised. More significant elevation is consistent with bile duct obstruction
LFTs - elevated alkaline phosphate is consistent with bile duct obstruction
Serum lipase or amylase - identify or exclude acute pancreatitis
Blood cultures - if infection is suspected
Cholelithiasis (gallstones) gold standard investigations
Abdominal ultrasound scan
- may show gallstones, distended gallbladder, thickened gallbladder was
May follow up with MRCP if no bile duct stone seen
Endoscopic retrograde cholangiography - better but less commonly used
Cholelithiasis (gallstones) differential diagnosis
Acute cholangitits: classic findings are fever and chills, jaundice and abdominal pain (charcot’s triad)
Chronic cholecystitis
Peptic ulcer disease
Acute pancreatitis - serum amylase and lipase, inflammation on CT scan
Cholelithiasis (gallstones) management
Analgesia
IV fluids if needed
Antiobiotic therapy (if suspected sepsis)
Laparoscopic cholecystectomy
Percutaneous cholecystostomy if unfit for anaesthesia and surgery
Cholelithiasis (gallstones) prognosis
Intreated acute acalculous cholecystitis has mortality up to 50%
Acute cholangitis defintiion
Previously known as ascending cholangitis, acute cholangitis is an infection of the biliary tree most commonly used by obstruction
Acute cholangitis aetiology
- most common aetiology is cholelithiasis (gallstones) leading to choledocholithiasis (gallstones in the bile duct) and biliary obstruction
- iatrogenic biliary injury leading to strictures of the biliary tree
- sclerosing cholangitis cause up to a quarter of cases
- chronic pancreatitis (with stenosis and stricture of the distal common bile duct)
- radiation-induced biliary injury
- complication of chemo
Acute cholangitis risk factors
Age, gallstones, strictures, surgery on the biliary system
Acute cholangitis pathophysiology
Obstruction of the common bile duct initially results in bacterial seeding of the biliary tress, possibly via the portal vein, and when combined with bacterial contamination, can lead to acute cholangitis. As the bile duct pressure increases, extravasation of the bacteria into the bloodstream occurs. If not recognised and treated this will lead to sepsis.
Acute cholangitis key presentations
Classic presentation is Charcot’s triad: fever jaundic and right upper quadrant pain. Pale stool, pruritus (itch associated with liver disease)
Acute cholangitis 1st line investigations
Transabdominal ultrasound - if there are signs of severe cholangitis or patient is high risk for sepsis
Subsequent abdominal CT scan if ultrasound is inconclusive.
Bloods
- FBC - look at white count
- coagulation profile - PT may be raised with sepsis
- CRP - raised
- LFTs - raised
- U&Es - raised urea with severe disease
- blood cultures - usually gram -ve
Arterial blood gas including lactate is spesis is suspected - low bicarbonate with raised anion gap; metabolic acidosis; raised lactate
Acute cholangitis gold standard investigations
All patients will eventually need biliary decompression most commonly using endoscopic retrograde cholangiopancreatography (ECRP)
Acute cholangitis differential diagnosis
Acute cholecystitis - patients with cholangitis typically have diffuse RUQ pain and not classic Murphy’s sign
Acute cholangitis management
1st line:
- RCP
2nd line:
- surgical biliary decompression
Acute cholangitis complications
Acute pancreatitis, inadequate biliary drainage (symptoms likely to presist and/or worsen), hepatic abscess
Acute cholangitis prognosis
Good in most patients with adequate biliary drainage
Primary biliary cholangitis defintion
A chronic disease of the small intrahepatic bile ducts characterised by progressive bile duct damage (and eventual loss) occurring in the context of chronic portal tract inflammation. Fibrosis develops as a consequence of the initially insult and the secondary effects of bile acids retained in the liver ultimately resulting in cirrhosis.
Primary biliary cholangitis aetiology
Conventially thought to be an autoimmune disease. Very high incidence of anti-mitochondrial antibodies (over 95% of patients)
Primary biliary cholangitis risk factors
Much more common in women (10:1 F:M), usually presents 55-65yrs. Family history of other autoimmune disease
Primary biliary cholangitis pathophysiology
Progressive damage and destruction of the biliary epithelial cells lining the small intrahepatic bile ducts. Bile ducts are damaged in the context of portal tract inflammation. Bile duct loss is progressive and in the end stages there can be a complete loss of small intrahepatic ducts.
Loss of bile duct cross-sectional area within the liver leads to cholestasis (blocked bile ducts) with bile acid retention. This can cause secondary liver damage which further contributes to bile duct loss.
Fibrosis occurs due to progressive damage and this can lead to cirrhosis. Can also have associated hepatitis.
Primary biliary cholangitis signs and symptoms
Asymptomatic patients are discovered on routine examination or screening to have hepatomegaly, a raised alkaline phosphatase or autoantibodies.
May have significant history of hypercholesterolemia.
Pruritus is usually the first symptom preceding jaundice by a few years. Fatigue may accompany pruritus.
When jaundice appears it is usually associated with hepatomegaly.
In later stages, pruritus is severe and patients are jaundiced.
Pigmented xanthelasma on eyelids may be present as well as cholesterol deposits in the creases of the hands.
Primary biliary cholangitis 1st line investigations
Anti-mitochondrial antibodies - present in 95%, M2 is specific
Serum alkaline phosphatase - high, often only abnormality in biochemistry
Serum cholesterol - raised
Globulins - IgM is raised
Ultrasound - diffuse alteration in live architecture. Obstructuve duct lesions should be excluded.
Liver biopsy - granulomas often present although not specific.
Primary biliary cholangitis differential diagnosis
Obtrsuctive bile duct lesion
Sclerosing cholangitis
Drug induced cholestasis
Infiltrative malignancy within liver
Primary biliary cholangitis management
1st line:
- bile acid analogue - ursodeoxycholic acid
- immunomodulatory therapy - prednisolone
- antipruitic treatment (if needed) - colestyramine
End stage:
- liver transplant
Primary biliary cholangitis complications
- Hypercholesterolemia
- Osteoporosis
- Portal hypertension seocndary to cirrhosis
Acute and chronic pancreatitis definition
Defined by pancreatic inflammation. Not always clinically distinguishable between acute and chronic forms. Acute pancreatitis is a self-limiting and reversible pancreatic injury associated with med-epigatric pain and elevated serum pancreatic enzymes whereas chronic pancreatitis is characterised by recurrent or persistent abdominal pain and progressive injury to the pancreas or persistent abdominal pain and progressive injury leading to scarring and loss of function.
For patients with recurrent attacks of pancreatitis, the cause and type involves distinguishing between 4 entities:
1. recurrent acute pancreatitis: identifiable cause of acute pancreatitis that does not lead to chronic pancreatitis (eg gallstones, drugs, hypercalcemia etc)
2. idiopathic pancreatitis: exhaustive evaluation identifies no cause. Most commonly represents chronic relapsing pancreatitis or define chronic pancreatitis
3. chronic relapsing pancreatitis: patients have relapsin pain not recognised as chronic pancreatitis but have pathological changes in tissue specimens
4. established chronic pancreatitis: hallmark features including reduced exocrine function of the pancreas, malabsorption, diabetes and pancreatic calcifications
Acute and chronic pancreatitis aetiology
Acute pancreatitis (GET SMASHED):
- G: gallstones
- E: ethanol
- T: trauma
- S: steroids
- M: mumps
- A: autoimmune eg SLE
- S: scorpion bites (rare)
- H: hypercalcemia, hypothermia, hyperlipidemia
- E: ERCP
- D: drugs - eg azathioprine, metronidazole, tetracycline, furosemide
Chronic pancreatitis: Main ones are alcohol and idiopathic. TIGAR-O classification - T-toxic-metabolic eg alcohol, smoking - I-idiopathic - G-genetic - A-autoimmune - R-recurrent and severe acute pancreatitis - O-obstructive
Acute and chronic pancreatitis risk factors
Acute: middle aged women (due to gallstones), young-middle aged men (due to alcohol)
Chronic: alcohol, smoking, family history, coeliac disease
Acute and chronic pancreatitis key presentations
Acute:
Usually presents with severe, constant supper abdominal pain (epigastric or LUQ), usually sudden in onset and often radiating to the back with associated nausea/vomiting in 80% of patients
Hypoxaemia
Hyperlipidaemia
Late stage - haemorrhagic
- Grey-turner’s sign (bruising of the flanks)
- Cullen’s sign (oedema and bruising around the umbilicus)
Chronic:
Hallmark clinical features:
- abdominal pain (epigastric, dull, radiates to the back)
- jaundice (rare)
- nausea/vomiting
- decreased appetitie
- exocrine dysfunction: malabsorption with weight loss, diarrhoea, steatorrhoea and protein deficiency
- endocrine dysfunction: diabetes mellitus
Acute and chronic pancreatitis signs and symptoms
Additional non-specific symptoms:
Weight loss, micro-nutrient deficiencies, nausea and vomiting, skin nodules, painful joints, abdo distension, SOB
Acute and chronic pancreatitis 1st line investigations
Acute:
serum lipase or amylase (lipase is better)
FBC - leukocytosis (sepsis), may have raised haematocrit
CRP - may be elevated
LFTs - elevated ALT suggestive of gallstones
Transabdominal ultrasound - looks for gallstones may show pancreatic inflammation
Chronic:
Blood glucose - may be elevated due to insulin resistance
CT - look for pancreatic clarifications or enlargement
Abdo ultrasound
Acute and chronic pancreatitis management
Acute: will vary on aetiology
- fluid resuscitation
- analgesia - may need opioids
- antiemetic - ondansetron
- IV antibiotics if infection strongly suspected or proven
- ERCP if cholangitis is present
- cholecystectomy of gallstones present
Chronic: (for chronic symptoms)
- analgesia
- pancreatic enzyme supplements plus PPIs
- treat underlying cause
Acute and chronic pancreatitis complications
Sepsis, DIC, ARDS
Alcoholic liver disease (ALD) definition
Caused by chronic heavy alcohol ingestion. Alcoholic liver disease has 3 stages of liver damage:
- fatty liver (steatosis)
- alcoholic hepatitis (inflammation and necrosis)
- alcoholic liver cirrhosis
Alcoholic liver disease aetiology
The common aetiological denominator is chronic and heavy alcohol ingestion. Only about 10-20% of chronic heavy drinkers develop severe forms such as alcoholic hepatitis and cirrhosis. The risk increases for obese patients and the progression to fibrosis and even hepatocellular carcinoma is quicker in patients who smoke.
Alcoholic liver disease risk factors
Prolonged and heavy alcohol consumption, hepatits C, female sex, cigarette smoking, obesity
Alcoholic liver disease pathophysiology
Alcohol is mainly metabolised in the liver by alcohol dehydrogenase and cytochrome P-450 2E1. Alcohol dehydrogenase and acetaldehyde dehydrogenase (a metabolite of alcohol) reduce NAD to NADH. Excessive NADH in relation to NAD in the liver inhibits gluconeogenesis and increased fatty acid oxidation, which in turns promotes fatty infiltration in the liver.
Alcohol metabolism also causes an increased production of free radicals
Chronic alcohol exposure activates metabolism in hepatic macrophages which produce tissue necrosis factor (TNF-alpha) and induce production of reactive oxygen species in mitochondria.
Alcoholics are usually deficient in antioxidants such as glutathione and vitamin E. therefore oxidative stress promotes hepatocyte necrosis and apoptosis in these patients. Free radials can also induce lipid peroxidation, causing inflammation and fibrosis. Alcohol metabolites may also induce inflammation. Acetaldehyde damages liver cell membranes. Alcohol also affects the barrier function of intestinal mucosa, producing endotoxemia, which leads to hepatic inflammation.
Alcoholic liver disease key presentations
Patients may be asymptomatic with elevated AST and ALT.
Alcoholic liver disease signs and symptoms
Presence of risk factors
Abdo [ain - RUQ discomfort is common with acute alcoholic hepatitis
Hepatomegaly - may be present with alcoholic fatty liver (steatosis) or alcoholic hepatitis. Hepatomeglay may be a sign in a liver cirrhosis patients suggesting hepatocellular carcinoma
Ascites - very common clinical complication of cirrhosis
Weight loss or weight gain
Alcoholic liver disease 1st line investigations
GGT - more sensitive than AST or ALT for alcoholic liver disease - elevated
AST & ALT - often raised, AST almost always elevated. Classic ration of AST/ALT >2 seen in most causes. Reversal of the ratio suggests viral hepatitis or possible non-alcoholic fatty liver disease
FBC - anaemia and leukocytosis often present
Hepatic ultrasound - may show hepatomegaly, fatty liver, liver cirrhosis, liver mass, splenomegaly, ascites, portal hypertension
Alcoholic liver disease differential diagnosis
Viral hepatitis (B, C, A) Cholecystitis - asses murphy's sign Acute liver failure - will see severe elevation of AST and ALT with prolonged PT Co-existing diseases due to alcohol: - acute/chronic pancreatitis - Mallory-Weiss tear - alcohol withdrawal - delirium tremens
Alcoholic liver disease management
- Alcohol abstinence and withdrawal management
- weight reduction and smoking cessation
- nutritional supplementation and multivitamins - malnutrition rates very high in ALD
- immunisation
- corticosteroids
- salt restriction and diuretics for ascites
- pentoxifylline - may reduce risk of death
Alcoholic liver disease complications
High risk of hepatic encephalopathy and portal hypertension
Non-alcoholic fatty liver disease (NAFLD) definition
Also known as non-alcoholic hepatic stenosis. It is a clinico-histopathological entity that includes a spectrum of conditions characterised histologically by microvascular hepatic steatosis in those who do not consume alcohol in amounts considered harmful to the liver.
Non-alcoholic fatty liver disease aetiology
Risk factors also include medications, surgical procedures and total parenteral nutrition and are considered secondary cuases. Primary NAFLD includes people with NAFLD associated with metabolic syndrome or insulin resistance
Non-alcoholic fatty liver disease risk factors
Obesity, insulin resistance or diabetes, dyslipidemia, hypertension
Non-alcoholic fatty liver disease pathophysiology
Most widely help hypothesis implicates insulin resistance as the key mechanism leading to excessive triglyceride accumulation in the liver and subsequent development of hepatic steatosis. Once steatosis is present, some have proposed a second hit or additional oxidative injury, which is needed for the necrosis-inflammatory component seen in steatohepatitis. Antioxidant deficiency; hepatic iron; fat derived hormones including leptin, adiponectin and resistin; and intestinal bacteria have all been implicated as potential oxidative stressors. Non-alcoholic steatohepatitis (NASH) is therefore a more advanced form of NAFLD. NASH with fibrosis may progress to cirrhosis and liver failure.
Non-alcoholic fatty liver disease key presentations
Presence of risk factors: see above
Non-alcoholic fatty liver disease signs and symptoms
Absence of significant alcohol use Fatigue and malaise Hepatosplenomegaly - hepatomegaly seen in around half of patients at presentations. No uncommon for the liver to shrink and the spleen to continue ti enlarge as the disease advances. Truncal obesity RUQ abdominal discomfort
Non-alcoholic fatty liver disease 1st line investigations
Serum AST and ALT - usually high, AST:ALT is typically <1.
Differs from acute alcohlic hepatitis. Ratio reversal in patients with NASH may indicate more advance fibrosis.
Alkaline phosphatase - can be elevated
GGT - may be elevated
FBC - anaemia or thrombocytopenia
Enhanced liver fibrosis test - for advanced liver fibrosis
Cirrhosis definition
The pathological end-stage of any chronic liver disease. Cirrhosis is a diffuse pathological process, characterised by fibrosis and conversion of normal liver structure to abnormal nodules known as regenerative nodules.
It can arise from a variety of causes. It can lead to portal hypertension, liver failure and hepatocellular carcinoma. It is generally considered irreversible in the advance stages although significant recovery can occur if the underlying cause is treated.
Can be described as:
- compensated - liver can still function effectively and there are no, or few noticeable clinical symptoms
- decompensated - liver is damaged to the point that it cannot function adequately and overt clinical complications (such as jaundice, ascites, variceal hemorrhage and hepatic encephalopathy) are present
- events causing decompensation include infection, portal vein thrombosis, and surgery
- at point of decompensation, it is known as chronic decomensated hepatic failure
Cirrhosis aetiology
Can derive from any chronic liver disease. Most common causes in the West are: ALD, NAFLD (with associated steatohepatitis) and chronic viral hepatitis.
When the aetiology can’t be determined it is considered ‘cryptogenic’. This is less common now.
Some other causes:
- metabolic disorders: hemochromatosis, wilson’s disease, alpha-1 antitrypsin deficiency
- cholestatic and autoimmune liver diseases
- biliary obstruction
Cirrhosis risk factors
Alcohol misuse, IV drug use, unprotected sex, obesity
Cirrhosis pathophysiology
Hepatic fibrosis can occur with any type of chronic liver injury and may evolve into cirrhosis with nodule formation. Hepatic fibrosis is characterised by the accumulation of collagen in the space of dissent.
This process perturbs blood through the live leading to increased pressure in the portal venous system as well as shunting blood away from the liver. Acute insult such as infection can cause changes to the vascular toe of the liver influences portal pressure and result in acute decompensation. This is called acute-on-chronic liver failure.
These changes lead to portal hypertension, which underlies the development of ascites and gastro-oesophageal varies and promotes the diversion of nutrient-carrying blood away from the liver, contributing to hepatic encephalopathy.
Cirrhosis can lead to malnutrition, and most importantly sarcopenia (progressive loss of skeletal muscle). Hepatocellular carcinoma is more likely to occur in the pro-oncogenic environment of cirrhosis.
Cirrhosis has potential for reversibility if the ongoing liver injury is halted. If it is irreversible then transplant is likely needed.
Cirrhosis key presentations
Presence of risk factors
Cirrhosis signs and symptoms
Abdominal distention - symptom of decompensated cirrhosis secondary to ascites in portal hypertension
Jaundice and pruritus - suggestive of decompensated cirrhosis secondary to reduced hepatic excretion of conjugated bilirubin into the biliary tree. Pruritus is secondary to impaired bile secretion.
Haematemesis (blood in vomit) and melaena (blood stool) - symptoms of decompensated cirrhosis secondary to GI haemorrhage from gastro-oesophageal varices in portal hypertension
Hand and nail features - leukonychia, palmar erythema and spider naevi
Facial features - telangiectasia, spider naevi, jaundiced sclera
Cirrhosis 1st line investigations
Transient elastography for alcoholic cause/hep C NAFLD with high ELF test
Liver biopsy otherwise
Bloods:
- LFTs - ALT levels are greater than AST in most chronic liver disease (except alcohol-related). Alkaline phosphatase and GGT may be raised due to cholestasis. Bilirubin may be high in decompensation
- albumin - low
- serum sodium - hyponatremia is common due to associated ascites and worsens as liver disease progressed
- PT time - prolonged due to hepatic synthetic dysfunction
- platelets - reduced
- antibodies to heapatitis C virus
- hepatitis B surface antigen
Cirrhosis management
Treat underlying cause and prevent superimposed hepatic insult - avoid alcohol, NSAIDs, high dose paracetamol, needs immunisation against hep A and B, influenza, pneumococci
Sodium restriction and diuretic therapy for ascites
Liver transplant for end stage disease
Cirrhosis monitoring
Screen for hepatocellular carcinoma every 6 months
Upper GI endoscopy for oesophageal varices
Oesophageal varices definition
Oesophageal varices are dilated collateral blood vessels that develop as a complication of portal hypertension, usually in the setting of cirrhosis.
Oesophageal varices aetiology
Portal hypertension
Oesophageal varices pathophysiology
These vessels are thin and not meant to transport high pressure blood, they can rupture easily. Rupture causes haematemesis. Rupture causes blood digested leading to melaena.
Oesophageal varices clinical manifestations
Haematemesis, melaena, haematochezia (passage of fresh blood through the anus)
Often found on routine endoscopy in at risk patients
Oesophageal varices investigations
Upper GI endoscopy
Investigate cause of portal hypertension
Oesophageal varices management
Medical
- BBs to lower cardiac output and therefore portal pressure
- nitrates to reduce portal pressure
- terlipressin - ADH analogue - cause vasoconstriction of mesenteric arterioles and thereby reducing inflow to the portal venous system and therefore portal pressure and by extension portosystemic collaterals such as oesophageal varices
Surgical
- band ligation
Hepatitis A/B/C/D/E/autoimmune definition
Inflammation of the liver due to a variety of causes.
A is acquired by mouth from anus, is always cleared acutely and only ever appears once
E is even in England and can be eaten (sausage from pigs), if not always beaten
B is blood-borne and if not beaten can be bad
B and D is BastarDly
C is usually chronic but can be cured - at a cost
Hepatitis A/B/C/D/E/autoimmune aetiology
Viral:
A: faecal-oral spread (normally with travel history), RNA virus, causes acute hepatitis
B: blood-borne, DNA virus, can be acute or chronic
C: blood-borne, RNA virus, can be acute or chronic
D: blood-borne, combines with B (can only propagate in the presence of hep B), RNA virus, can be acute or chronic
E: faeco-oral spread, contaminated food or water, endemic in UK - found in undercooked pork, RNA virus, causes acute hepatitis
Autoimmune: genetics, viral triggers, auto-antigens, dysfunction of immunoregulatory mechanisms. Can be acute or chronic
Hepatitis A/B/C/D/E/autoimmune risk factors
Autoimmune: more prevalent in women, concurrent autoimmune diseases often present
Hepatitis A/B/C/D/E/autoimmune clinical manifestations
HAV, HBV and HCV can all result in acute illness with symptoms of nausea, abdominal pain, fatigue, malaise and jaundice, HBV and HCV can also lead to chronic infection.
HDV only replicates in liver cells so cellular damage mainly occurs in the liver.
Hepatitis A/B/C/D/E/autoimmune 1st line investigations
Viral
- for HAV: bloods
- AST/ALT raised
- raised IgG and IgM
Hepatitis A/B/C/D/E/autoimmune management
VIral hepatitis
- vaccines available: A (for travellers) and B (immunisation)
- treatment for types A&E: supportive as they are self limiting
- treatment for B: regulated interferon-a 2a = Pegasus (stimulates immune response)
- treatment for chronic C: antiviral: velpatasvir/sofosbuvir
Autoimmune hepatitis:
Immunosuppression: prednisolone and azathioprine
Hepatitis A/B/C/D/E/autoimmune monitoring
Chronic hepatitis carrier remain infectious and may transmit the disease for many years
Hepatitis A/B/C/D/E/autoimmune complications
Chronic hepatitis may lead to cirrhosis and hepatocellular carcinoma
Haemochromatosis definition
A multisystem disorder of dysregulated dietary iron absorption and increased iron release from macrophages
Haemochromatosis aetiology
Autosomal recessive (mutations in HFE gene in chromosome 6)
Haemochromatosis risk factors
Most common in white British and Irish populations
Haemochromatosis pathophysiology
In advanced cases iron accumulates in organs including liver, heart, anterior pituitary, pancreas, joints and other organs
Haemochromatosis signs and symptoms
Arthralgias due to pseudo-gout
Diabetes mellitus is common
Skin bronzing
Hepatomegaly (associated with cirrhosis)
Haemochromatosis complications
Restrictive cardiomyopathy due to iron deposition
Bronze diabetes
Wilson’s disease definition
Disease of copper accumulation and copper toxicity
Wilson’s disease aetiology
Autosomal recessive (ATP7B in chromosome 13)
Wilson’s disease risk factors
Patients are usually 10-40yrs
Family history
Wilson’s disease pathophysiology
Damage due to oxidant damage caused by excess free copper. Caruloplasmin is made in the liver and is the major copper-carrying protein in the blood.
Basal ganglia and areas of the brain that coordinate movement are most sensitive to copper accumulation
Wilson’s disease signs and symptoms
Kayser-Fleischer rings (copper rings in the eyes)
Neurological signs
- behavioural abnormalities
- tremor
- incoordination
- dysarthria (slurred or hypokinetic speech)
- dysdiadochokinesis
Wilson’s disease 1st line investigations
Serum ceruloplasmin - low
Wilson’s disease management
Penicillamine to excrete copper
Reduce copper intake (shellfish)
Wilson’s disease complications
Liver failure, oesophageal varices
Wilson’s disease prognosis
Good if treatment is started early
Alpha-1 antitrypsin deficiency definition
Ineffective activity of the specific protease inhibitor alpha-1 antitrypsin, which is the enzyme responsible for neutralising neutrophil elastase and preventing inflammatory tissue damage in the lungs. Variants of the enxyme may polymerise and accumulate in the liver, resulting in hepatic failure.
Alpha-1 antitrypsin deficiency aetiology
Autosomal recessive (SERPINA1 in chromosome 14)
Alpha-1 antitrypsin deficiency risk factors
Family history of AAT deficiency
Alpha-1 antitrypsin deficiency pathophysiology
Results in reduced AAT plasma levels causing inflammatory responses within the lung. Inflammation of the lung in AAT deficiency is exacerbated by cigarette smoking
Alpha-1 antitrypsin deficiency signs and symptoms
COPD symptoms
May have hepatomegaly, ascites
Alpha-1 antitrypsin deficiency 1st line investigations
Plasma AAT level: reduced
Alpha-1 antitrypsin deficiency management
MAnage COPD
Hepatitis vaccination
AAT augmentation therapy
If hepatic manifestations are present a liver transplant may be needed
Liver/pancreatic cancer definiton
Hepatocellular carcinoma (HCC): also known as hepatoma, is a primary cancer arising from hepatocytes in predominantly cirrhotic liver. However some patients may not have cirrhosis, especially those with chronic hepatitis B.
Pancreatic cancer: refers to primary pancreatic ductal adenocarcinoma which accounts for the vast majority of pancreatic neoplasms.
Liver/pancreatic cancer aetiology
Contributes to HCC:
- cirrhosis
- heavy alcohol consumption
- viral hepatitis
- DM
- obesity
- haemochromatosis
- alpha-1 antitrypsin deficiency
- primary biliary cholangitis
- primary sclerosis cholangitis
Pancreatic cancer: the only consistently reported exogenous risk factor is cigarette smoking. Thought to have a genetic component.
Liver/pancreatic cancer pathophysiology
Pancreatic cancer: most are located within the head of the pancreas. Lymph node metastases are common as well as perineurial and vascular invasion.
Liver/pancreatic cancer signs and symptoms
HCC: presence of risk factors, older age, abdominal distension, general liver symptoms
Pancreatic: painless jaundice with weight loss = cancer fo head of the pancreas
Liver/pancreatic cancer 1st line investigations
Hepatocellular carcinoma:
- ultrasound of liver
- CT/MRI liver
- biopsy
- raised alpha fetoprotein (AFP) - elevated in 60% of HCC patients typically in advanced disease. Mild elevation may occur in chronic hepatitis without HCC
- bloods: clotting abnormalities, deranged LFTs (elevated aminotransferases and bilirubin with low albumin)
Pancreatic cancer:
- abdominal USS - do without delay, has high sensitivity for most pancreatic tumours. Normal ultrasound does not exclude cancer.
- pancreatic protocol CT
- LFTs: demonstrates degree of obstructive jaundice
- cancer antigen (CA) 19-9 biomarker - elevated
Liver/pancreatic cancer management
Hepatocellular carcinoma
- surgical resection
- radio frequency ablation
- TACE (injection of anticancer drugs into the hepatic artery), chemo
Pancreatic cancer
- surgical resection (if possible) with enzyme replacement
- chemo
Liver/pancreatic cancer complications
HCC: biliary obsturction, cachexia (extreme weight loss and muscle wasting), non-diabetic hypoglycaemia, hepatic failure
Liver/pancreatic cancer prognosis
HCC: poor, 5-yr survival for patients with symptomatic HCC is 0-10%
Pancreatic: generally poor
Ascites definition
A pathological collecting of fluid in the peritoneal cavity
Ascites aetiology
Most common cause is cirrhosis (linked to associated portal hypertension), accounting for 75-80% of cases
Other causes include congestive heart failure, alcoholic liver disease and other liver disease
Can be due to transudate (due to increased pressure in the portal vein) or exudate (actively secreted fluid due to inflammation or malignancy)
Ascites pathophysiology
In cirrhosis - peripheral arterial vasodilation (controlled by NO, other vasodilatiors) - leads to reduction in effective blood volume
Activation of sympathetic system and RAAS, promoting salt and fluid retention
Oedema formation is encouraged by hypoalbuminemia and mainly localised to the peritoneal cavity due to portal hypertension
Ascites presentation
May experience early satiety and SOB
Most useful finding is flank bulging and shifting dullness to percussion
Ascites diagnosis
Ultrasound, ideally doppler
Ascitic tap: culture, gram stain, cytology, protein
- transudate: clear fluid, albumin 11g/L or more below serum albumin
- exudate: cloudy fluid, less than 11g/L below serum albumin
Ascites management
Restrict fluid and sodium
Spironolactone
Treat underlying cause
Spontaneous bacterial peritonitis (SBP) definition
SBP is an infection of the ascitic fluid that cannot be attributed to any inta-abdominal, ongoing inflammatory or surgically correctable condition. It is frequently encountered in patients with cirrhosis
Spontaneous bacterial peritonitis (SBP) aetiology
Most common cause is gram-negatibe bacteria. Most common source of the bacteria is intestinal
- eschericha coli
- klebsiella pneumoniae
- enterococcus aureus
- streptococcus pneumoniae
Spontaneous bacterial peritonitis (SBP) presentation
Symptoms: abdo pain or tenderness, altered mental status (hepatic encephalopathy)
Signs: pyrexia (hypothermia, hypotension and tachycardia may be present if spetic), signs of ascites, vomiting, diarrhoea, GI bleed
Spontaneous bacterial peritonitis (SBP) diagnosis
Ascitic tap
- ascitic fluid neutrophil count (ANC) - raised
- fluid appearance: hazy, cloudy or bloody
- ascitic gram staining and cultures
Spontaneous bacterial peritonitis (SBP) management
Cefotaxime
Secondary prevention
- prophylactic ciprofloxacin
- beta blockers
Spontaneous bacterial peritonitis (SBP) complications
Sepsis/septic shock
Paracetamol overdose defintion
Excessive paracetamol consumption leading to toxicity
Paracetamol overdose aetiology
Uses up glutathione stores that are used to metabolism paracetamol into non-harmful substances. Afteroverdose, CYP2E1 becomes important in creating the harmful metabolite NAPQI which is nroamlly combines with glutathione. Buikld up of NAPQI causes mitochondrial injury and death of hepatocytes and may be enough to cause acute liver injury as well as variable degrees of renal injury
Paracetamol overdose presentation
Nausea and vomiting, anorexia, RUQ abdo pain. History of self harm. Glutathione deficiency due to eating disorders and alcohol use etc
Paracetamol overdose diagnosis
Serum paracetamol concentration
LFTs - may be raised
Blood glucose - may be hypoglycaemia due to ALI
ABG or VBG - may show lactic acidosis
Paracetamol overdose management
N-acetyl-cysteine (precurosor to glutathione) with antiemetic
Activated charcoal
