Liver and friends Flashcards
What is alcoholic liver disease?
Liver manifestations of alcohol overconsumption
What are the main causes of alcoholic liver disease?
Alcohol abuse
Genetic predisposition
Immunological mechanisms
How does fatty liver occur?
Metabolism of alcohol produces fat in liver
Minimal with small amounts of alcohol, but with larger amounts, cells become swollen and fat
No liver cell damage
Collagen laid down around central hepatic veins and can progress to cirrhosis without preceding hepatitis
Alcohol directly affects stellate cells, transforming them into collagen-producing myofibroblast cells
How does alcoholic hepatitis occur?
Infiltration of polymorphonuclear leucocytes and hepatocyte necrosis
Dense cytoplasmic inclusions called Mallory bodies sometimes seen in hepatocytes and giant mitochondria also a feature
If alcohol consumption continues, alcoholic hepatitis can progress to cirrhosis
How does alcoholic cirrhosis occur?
Micronodular type but mixed pattern also seen accompanying fatty change and evidence of pre-existing alcoholic hepatitis may be present
How does fatty liver present?
Often no symptoms/signs
Vague abdominal symptoms of nausea, vomiting, diarrhoea, due to more general effects of alcohol on GI tract
Hepatomegaly
How does alcoholic hepatitis present?
Well with few symptoms
Only apparent of liver biopsy in addition to present change
Mild-moderate symptoms of ill-health
Signs of chronic liver disease
Liver biochemisty deranaged and diagnosis made on liver histology
Abdominal pain present
High fever associated with liver necrosis
Deep jaundice
Hepatomegaly
Ascites with ankle oedema
How does chronic liver disease present?
Ascites
Bruising
Clubbing
Dupuytren’s contracture
How does alcoholic cirrhosis present?
Final stage of liver disease from alcohol use Very well with few symptoms Signs of chronic liver disease Diagnosis confirmed by liver biopsy Alcoholic dependency features
How is fatty liver diagnosed?
Elevated MCV indicated heavy drinking
Raised ALT/AST
USS/CT will demonstrate fatty infiltration as well as liver histology
How is alcoholic hepatitis diagnosed?
Leucocytosis
Elevated - serum bilirubin, AST/ALT, alkaline phosphatase, prothrombin time
How is alcoholic cirrhosis diagnosed?
Same as hepatitis
How is alcoholic liver disease treated?
Stop drinking alcohol - treat delirium tremens with diazepam
IV thiamine prevents Wernicke-Korsakoff encephalopathy which occurs from alcohol withdrawal, occurs 6-24 hours after last drink and lasts up to a week
Diet high in vitamins and proteins
What is delirium tremens?
Deadly form of alcohol withdrawal
Involves sudden and severe mental or nervous system changes
Can lead to CVS collapse
How does delirium tremens present?
Confusion Body tremors Changes in mental function Agitation, irritability Deep sleep, lasting for days Excitement or fear Hallucinations
What is Wernicke-Korsakoff encephalopathy?
Cause by a deficiency in B vitamin thiamine
Thiamine helps metabolise glucose for brain
Lack of B1 common in alcoholics
How does Wernicke-Korsakoff encephalopathy present?
Confusion
Changes to vision
What happens when you treat fatty liver?
Fat will disappear and things will go back to normal
How is alcoholic hepatitis treated?
Nutrition maintained with enteral feeding and if necessary, vitamin supplementation
Steroids - short term benefit
Infections treated and/or prevented - anti-fungal prophylaxis
Stop drinking alcohol for liver
How is alcoholic cirrhosis treated?
Reduce salt intake
Stop drinking for life
Avoid aspirin and NSAIDs
Liver transplantation
What is alpha-1 antitrypsin deficiency?
Inherited autosomal recessive conformational disease that can be fatal
Alpha-1 antitrypsin gene located on chromosome 14
Lack of inhibition of proteolytic enzyme - neutrophil elastase
When is alpha-1 antitypsin deficiency more common?
In Caucasians
How does alpha-1 antitrypsin deficiency affect the body?
Deficiency affects lung (emphysema) and liver (cirrhosis and hepatocellular carcinoma) - homozygous and heterozygous
Lack of protection from tissue damage in lung
How does homozygous alpha-1 antitrypsin deficiency present?
Liver disease in children Emphyesema in adults Cirrhosis Respiratory problems Liver disease in heterozygotes - small risk
How is alpha-1 antitrypsin deficiency diagnosed?
Low serum alpha-1 antitypsin levels
How is alpha-1 antitrypsin deficiency treated?
No treatment Treat complications Stop smoking Liver transplant if hepatic decompensation Manage emphysema
What is ascending cholangitis?
Ascending/acute cholangitis infection of biliary tree and most often occurs secondary to common bile duct obstruction by gallstones
What can cause ascending cholangitis?
Common bile duct obstruction by gall stones
Benign biliary strictures following biliary surgery
Cancer of head of pancreas resulting in bile duct obstruction
In Far East and Mediterranean biliary parasites can cause blockage and ascending/acute cholangitis
How does ascending cholangitis present?
Biliary colic
Fever with rigors, jaundice, RUQ pain
Jaundice cholestatic thus there is dark urine, pale stools and skin may itch
How is ascending cholangitis diagnosed?
Blood tests
- Elevated neutrophil count
- Raised ESR/CRP
- Raised serum bilirubin
- Raised serum alkaline phosphatase
- Aminotransferase levels high - ALTs higher than ASTs
Imaging
- Transabdominal USS showing dilatation of common bile duct, may show obstruction, distal common bile duct stones easily missed
- Magnetic resonance cholangiography
- CT - excludes carcinoma of pancreas, easier to spot pigmented stones
How is ascending cholangitis treated?
IV antibiotics - continued after biliary drainage until symptom resolution
Urgent biliary drainage using ERCP with sphincterotomy - removal of stones using basket or balloon, crushing of stones, stent placement
Surgery required for large stones
What is ascites?
Accumulation of free fluid within peritoneal cavity
How common is ascites?
10-20% survival 5 years from onset Signifies other serious illness Common complication of cirrhosis Common post-op Poor prognosis
What can cause ascites?
Local inflammation - peritonitis/intra-abdominal surgery, abdominal cancers, infection
Low protein - inability to pull fluid back into intravascular space, accumulates in peritoneum, hypoalbuminaemia, nephrotic syndrome, malnutrition
Low flow - cannot move through system, raised vessel pressure causing fluid to leak out of vessles, cirrhosis, Budd-Chiari syndrome, cardiac failure, constrictive pericarditis
What is Budd-Chiari syndrome?
Very rare condition - 1 in a million
Occlusion of hepatic veins that drain liver
What is the classical triad of symptoms of Budd-Chiari syndrome?
Abdominal pain
Ascites
Liver enlargement
What can increase your risk of getting ascites?
High Na diet
Hepatocellular carcinoma
Splanchnic vein thrombosis resulting in portal hypertension
How does ascites present?
History - length of time, drugs, weight loss, underlying cause
Abdominal swelling developing over days/weeks
Distended abdomen
Fullness in flanks, shifting dullness
Mild abdominal pain and discomfort
Severe pain suspicion of bacterial peritonitis
Respiratoy distress and difficulty eating accompany tense ascites
Scratch marks on abdomen due to itching due to jaundice
Peripheral oedema
How is ascites diagnosed?
Demonstrating shifting dullness
Diagnostic aspiration of 10-20ml of fluid using ascitic tap for raised WCC, gram stain, cultures, cytology to find malignancy, amylase to exclude pancreatic ascites
Protein measurement from tap - transudate (portal hypertension, constrictive pericarditis, cardiac failure, Budd-Chiari syndrome), exudate (malignancy, peritonitis, pancreatitis, peritoneal TB, nephrotic syndrome)
How is ascites treated?
Treat underlying cause
Reduce Na to help liver and reduce fluid retention
Increase renal sodium excretion
Diuretic of choice aldosterone antagonist as spares K+
Drain fluid - 5L at a time, relieve symptomatic tense ascites
Shunts - transjugular intrahepatic portosystemic shunt
What happens with a therapeutic dose of aspirin?
Metabolise salicylic acid by esterases in many tissues, especially liver
Further metabolised to salicyluric acid and slicyl phenolic glucuronide
What happens with an overdose of aspirin?
Two pathways saturated
Kidneys compensate by increasing renal excretion of salicylic acid - extremely sensitive to changes in urinary pH
Salicylates stimulates respiratory centre, increasing rate and depth of respiration inducing respiratory alkalosis
Compensatory mechanisms including renal excretion of bicarbonate and potassium resulting in metabolic acidosis
Salicylates also interfere with carbohydrate, fat and protein metabolism and disrupt oxidative phosphorylation, increasing concentrations of lactate, pyruvate and ketones bodies, contributing to metabolic acidosis
How does aspirin overdose present?
Respiratory alkalosis due to direct stimulation by salicyclic acid of central respiratory centres and then develop metabolic acidosis to compensate
Hyper/hypoglycaemia
Hyperventilation and tachypnoea - respiratory acidosis
Sweating, vomiting, dehydration, epigastric pain, tinnitus, deafness
Coma, convulsions
How is an aspirin overdose treated?
Severity dose related
Fluid and electrolyte replacement with special attention pain ot potassium supplementation
Partial correction with administration of IV Na bicarbonate
Severe cases - urine alkalinisation, enhances renal elimination of salicylate
Haemodialysis
What is cirrhosis?
End stage of all progressive chronic liver disease, once fully developed irreversibly
Associated clinically with symptoms and signs of liver failure and portal hypertension
Irreversible liver damage
Loss of normal hepatic architecture with bridging fibrosis and nodular regeneration
How is cirrhosis classified by size?
Mirconodular cirrhosis
- Regenerating nodules usually < 3mm in size with uniform involvement of liver
- Often caused by alcohol or biliary tract disease
Macronodular cirrhosis
- Vary in size, normal acini seen within larger nodules
- Chronic viral hepatitis
What can cause cirrhosis?
Chronic alcohol abuse Non-alcoholic fatty liver disease Hepatitis B+/-D Hepatitis C Primary biliary cirrhosis Autoimmune hepatitis - presents with high ALT Hereditary haemochromatosis Wilson's disease Alpha-1 antitrypsin deficiency Drugs - amiodarone, methotrexate
How does cirrhosis occur?
Chronic liver injury results in inflammation, matrix deposition, necrosis and angiogenesis leading to fibrosis
Liver injury causes necrosis and apoptosis, releasing cell contents and ROS
Activate hepatic stellate cells and Kupffer cells
Stellate cells release cytokines attracting neutrophils and macrophages to liver leading to further inflammation and therefore necrosis and eventual fibrosis
Kupffer cells phagocytose necrotic and apoptotic cells and secrete pro-inflammatory mediatorys
Increase myofibroblasts lead to progressive collagen matrix deposition resulting in fibrosis and scar accumulation in liver
Severe reduction in liver function as fibrosis non-functioning
Resolution of cause if fibrosis removed
Regression occurs, improving clinical outcomes
Regenerating nodules separated by fibrous septa and loss of lobular architecture within nodules
How does cirrhosis present?
Leuconychia - white discolouration on nails due to hypoalbuminaemia Clubbing Palmar erythema - red palms Duputren's contracture - flexed fingers Spider naevi Xanthelasma - yellow fat deposits under skin usually around eyelids Loss of body hair Hepatomegaly Bruising Ankle swelling and oedema Abdominal pain due to ascites
How is cirrhosis classified?
Child-Pugh classification
- Ascites, encephalopathy, high bilirubin, low albumin, long prothrombin given 1-3 and added up to give a score
- < 7 best > 10 bad prognosis
- Risk of variceal bleeding high > 8
How is cirrhosis diagnosed?
Liver biopsy - confirms diagnosis, type and severity
LFTFs -s erum albumin and prothrombin time (low and long)
Liver biochemistry
- Normal depending on severity
- Riased AST/ALT
- Serum electrolytes low
- Raised serum creatinine
- Alpha fetoprotein - hepatocellular carcinoma
Imaging
- USS - hepatomegaly, nodules, carcinoma
- CT - hepatosplenomegaly, carcinoma
- MRI - tumours
- Endoscopy - varices and portal hypertensive gastropathy
How is cirrhosis treated?
Good nutrition vital
Alcohol abstinence
6 monthly USS for early development of carcinoma
Treat underlying causes
Hep A and B vaccines
Acoid NSAIDs and asprin - maty precipitate GI bleed or renal impairment
Reduce salt intake
Liver transplant if advanced and does not respond to therapy
Name 4 possible complications of cirrhosis?
Coagulopathy - fall in clotting factors II, VII, IX and X
Encephalopathy
Hypoalbuminaemia resulting in oedema
Portal hypertension - ascites, oseophageal varices
What is drug induced liver injury?
Most common cause of acute liver failure in US
Usually resolution within 3 months of stopping drug
10% prolonged injury that can result in long term damage
What are the different types of drug induced liver injury?
Hepatic
Cholestatic eg jaundice
Immunological eg skin rashes, fever, arthralgia
Mechanism determines type of liver injury
Name 5 of the main drug causes for drug induced liver disease?
Antibiotics - augmentin, flucloxacillin, TB drugs, erythromycin CNS - chlorpromazine, carbamazepine Immunosuppressants Analgesics - diclofenac (NSAID) GI drugs - PPIs
How does drug induced liver injury occur?
Disruption of intracellular Ca2+ homeostasis
Disruption of bile canalicular transport mechanisms
Induction of apoptosis
Inhibition of mitrochondrial function, preventing fatty acid metabolism and accumulation of lactate and ROS
When does drug induced liver injury tend to occur?
Most occur within 3 months of starting durg
Onset within 1-12 weeks of starting
Damage may occur several weeks after stopping drug
How do you treat drug induced liver injury?
Monitor liver biochemisty essential in patients on long term treatment such as anti-tuberculosis therapy
Stop drug immediately
What is biliary colic?
Pain associated with temporary obstruction of cystic or common bile duct by a stone migrating from gall bladder, sudden onsey, severe but constant, crescendo characteristic
What is cholecystits?
Gallbladder inflammation
When do gall stones present?
At any age - uncommon before 30s Increased prevalence with age More common in women More common in Scandinavians, South Americans, Native North Americans, less common in Asian and African groups Most form in gall bladder Most asymptomatic
What can cause gallstones?
Obesity and rapid weight loss - diet high in animal fat and low in fibre
DM
Contraceptive pill
Liver cirrhosis
What are the risk factors for developing gall stones?
Female
Fat
Fertile - more kids increased risk of gallstones
Smoking
What are the 2 different types of gallstones?
Cholesterol - most
Bile pigment
How do cholesterol gallstones form?
Large, solitary stones
Cholesterol crystallisation in bile
Forms micelles and vesicles formed
Only form in bile with an excess of cholesterol due to - relative deficiency in bile salts and phospholipids, excess of cholesterol, reduced gallbladder motility and stasis (pregnancy, DM), crystalline promoting factors in bile
How do bile pigmented stones form?
Mainly formed of Ca2+ Small stones, friable and irregular Haemolysis main cause Black and brown Black stones - Calcium bilirubinate composition and network of mucin glycoproteins that interlace with salts - Glass-like cross-sectional surface - Haemolytic anaemia Brown stones - Calcium salts - Muddy hue with alternative brown and tan layer on cross-section - Almost always found in presence of bile stasis and/or biliary infection
How do gallstones present?
Mostly asymptomatic
Once symptomatic strong tend towards recurrent complications
Colicky pain - sudden onset, severe but constant, crescendo, over-indulgence of fatty foods, mid-evening onset lasting till early hours of morning
Epigastrium pain initially - localises to RUQ
Pain radiates to R shoulder and R subscapular region
Nausea and frequent vomiting
How does acute cholecystits present?
Inflammation of gall bladder Gall bladder distension Continuous epigastric pain with progression to severe localised RUQ pain - parietal peritoneal involvement Tender, muscle guarding, rigidity Vomiting, fever, local peritonitis
What is a differential diagnosis for biliary colic?
IBS, carcinoma, renal colic, pancreatitis
What is a differential diagnosis for acute cholecystitis?
Acute pancreatits, peptic ulceration, basal pneumonia, intrahepatic abscess
How is biliary colic diagnosed?
Unlikely significant abnormalities of lab tests
Abdominal USS
How is acute cholecystitis diagnosed?
Blood tests - raised WCC and CRP, serum bilirubin, alkaline phosphatase and aminotransferase levels
Abdominal USS - thick walled, shrunken gallbladder, pericholecystic fluid, stone
Examination - RUQ tenderness, Murphy’s signs - pain on taking deep breath when examiner places 2 fingers on RUQ
How do you treat gallstones?
Laproscopic cholecystectomy
Acute - nil by mouth, IV fluids, opiate analgesia, IV antibiotics, allow symptoms to subside then cholecystectomy
Stone dissolution - for cholesterol stones, increase bile content, oral ursodeoxycholic acid, cholesterol lowering agents (statins)
Show wave lithotripsy - directed to gallbladder stones to turn them into fragments, cystic duct required patency
What is hereditary haemochromatosis?
Inherited disorder of iron metabolism in which there is increased intestinal iron absorption leading to iron deposition in joints, liver, heart, pancreas, pituitary, adrenals, skin
In whom is hereditary haemochromatosis most common?
Most common single gene disorder in Caucasians
More common in males as menstrual blood loss is protective
Middle-aged men more frequently and severely affected than women
What causes hereditary haemochromatosis?
HFE gene mutation on chromosome 6, autosomal recessive gene - most common
Other gene mutations responsible - one autosomal dominant -not as common, sufferers can be heterozygous
High intake of iron and chelating agents
Alcoholics may have iron overload
What are the risk factors for hereditary haemochromatosis?
FHx
Alcoholic
How does hereditary haemochromatosis affect the body?
HFE gene protein interacts with transferrin receptor 1, mediator in intestinal iron absorption
Iron taken up by mucosal cells of small intestine inappropriately, exceeding binding capacity of transferrin
Hepatic expression of hepcidin gene decreased, facilitating iron overload
Excess iron taken up by liver and other tissues over a long period
Iron precipitates fibrosis
20-40g total body iron content
Particularly increased in liver and pancreas but also in other organs
Extensive iron deposition and fibrosis
Cirrhosis late feature
How does haemochromatosis present?
Most present in 50s
Tiredness and arthralgia early on
Hypogonasism secondary to pituitary dysfunction
Slate-grey skin pigmentation, signs of chronic liver disease, hepatomegaly, cirrhosis, dilated cardiomyopathy, osteoporosis
Cardiac manifestations - HF, arrhythmias common, especially in younger patients
Bronze skin pigmentation, DM
How is homozygous haemochromatosis diagnosed?
Raised serum Fe
Raised serum ferritin
Liver biochemistry often normal with established cirrhosis
