liver to work on Flashcards
Give 4 functions of the liver
- Glucose and fat metabolism
- Detoxification and excretion
- Protein synthesis (e.g. albumin, clotting factos)
- Bile production
Give 4 causes of hepatic jaundice
- Liver disease
- Hepatitis - viral, drug, immune, alcohol
- Ischaemia
- Neoplasm - HCC, mets
- Congestions - CCF
Give 3 causes of post-hepatic jaundice
Duct obstruction
- Gallstones
- Stricture - Malignancy, ischaemia, inflammatory
- Blocked stent
Give 3 symptoms of jaundice
- Biliary pain
- Rigors - indicate an obstructive cause
- Abdomen swelling
- Weight loss
Why are liver patients vulnerable to infection?
- Impaired reticuloendothelial function
- Reduced opsonic activity
- Leucocyte function
- Permeable gut wall
which conditions can cause Gallstones
- Obesity and rapid weight loss
- DM
- Contraceptive pill
- Liver cirrhosis
Give 4 symptoms of gallstones
Most are asymptomatic
- Biliary colic (sudden RUQ pain radiating to the back and epigastrium +/- nausea/vomiting) - AFTER EATING FATTY MEALS
- Acute cholecystitis (gallbladder distension –> inflammation, necrosis, ischaemia)
- Obstructive jaundice
- Cholangitis
- Pancreatitis
How can gallstones be removed from the gallbladder?
Laparoscopic cholecystectomy
ERCP with removal or destruction (mechanical lithotripsy) or stent placement
Bile acid dissolution therapy (for people not suitable for surgery)
Give 5 causes of acute liver disease
- Viral hepatitis
- Drug induced hepatitis
- Alcohol induced hepatitis
- Vascular - Budd-Chiari
- Obstruction
Give 5 causes of chronic liver disease
- Alcohol
- NAFLD
- Viral hepatitis (B,C,E)
- Autoimmune diseases
- Metabolic
- Vascular - Budd-Chairi
Give 5 signs of acute liver failure
- Jaundice
- Fetor hepaticus (smells like pears)
- Coagulopathy
- Asterixis - liver flap
- Malaise
- Lethargy
- Encephalopathy
Give 5 signs of chronic liver disease
- Ascites
- Oedema
- Bruising
- Clubbing
- Depuytren’s contracture
- Palmar erythema
- Spider naevi
What do the blood tests show in someone with liver failure?
Raised bilirubin Low glucose High AST and ALT Low levels of coagulation factors Raised prothrombin time High ammonia levels
Describe the treatment for liver failure
- Nutrition
- Supplements
- Treat complications
- Raised intracranial pressure = mannitol
- PPI = reduce GI bleeds
- bleeding = vitamin K
- encephalopathy = lactulose
- ascites = diuretics
- sepsis = sepsis 6, antibiotics - Liver transplant
Give 4 complications of of liver failure
- Hepatic encephalopathy
- Abnormal bleeding
- Jaundice
- Ascites
What drugs should be avoided in liver failure?
Constipators
Oral hypoglycaemics
Warfarin has enhanced effects
Opiates
What is cirrhosis?
Loss of normal hepatic architecture with fibrosis - liver injury causes necrosis and apoptosis- irreversible
Give 3 causes of cirrhosis
common:
- chronic alcohol abuse
- non-alcoholic fatty liver disease
- hepatitis
others
- haemochromatosis
- Wilson’s disease
- alpha-antitrypsin deficiency
Give 4 signs of cirrhosis
- ascites
- clubbing
- palmar erythema
- xanthelasma
- spider naevi
- hepatomegaly
- peripheral oedema
What investigations are done in someone with cirrhosis?
- Bloods = low platelets, high INR, low albumin
- US and CT - hepatomegaly
- liver biopsy - diagnostic
What is the treatment for liver cirrhosis?
- Good nutrition and alcohol abstinence
- Treat underlying cause
- Fluid and salt restriction for ascites –> spironolactone, furosemide, prophylactic ciprofloxacin
- liver transplant = definitive
- Screen for HCC - increased AFP
Give 4 complications of cirrhosis
Ascites
portal hypertension
- Decompensation
- SBP
- Increased risk of HCC
Give 3 causes of portal hypertension
- Pre-hepatic = blockage of hepatic portal vein before the liver (portal vein thrombosis)
- Hepatic = distortion of liver architecture (cirrhosis, schistosomiasis, Budd Chiari syndrome)
- Post-hepatic = venous blockage outside the liver (RHF, IVC obstruction)
what is the clinical presentation of portal hypertension?
- often asymptomatic
- splenomegaly
- spider naevi
- GI bleeding
- ascites
- hepatic encephalopathy
Name 4 conditions that can develop as a result of having hepatic encephalopathy
SAVE
- Splenomegaly
- Ascites
- Varices
- Encephalopathy
Give 4 causes of ascites and an example for each
- Local inflammation - peritonitis
- Leaky vessels - imbalance between hydrostatic and oncotic pressures
- Low flow - cirrhosis, thrombosis, cardiac failure
- Low protein - hypoalbuminaemia
Describe the pathophysiology of ascites
- Increased intra-hepatic resistance leads to portal hypertension –> ascites
- Systemic vasodilation leads to secretion of RAAS, NAd and ADH –> fluid retention
- Low serum albumin
Give 3 signs of ascites
- Distension
- Dyspnoea
- Shifting dullness on percussion
- Signs of liver failure
Describe the treatment for ascites
- Restrict sodium and fluids
- Diuretics - spirolactone
- Paracentesis
- Albumin replacement
Describe the effects of alcoholic liver disease
- Fatty liver –> hepatitis –> cirrhosis and fibrosis
- GIT –> gastritis, varices, peptic ulcers, pancreatitis , carcinoma
- CNS –> Degreased memory and cognition, wernicke’s encephalopathy
- Folate deficiency –> anaemia
- Reproduction –> testicular atrophy, reduced testosterone/progesterone
- Heart –> dilated cardiomyoapthy, arrhythmias
What might be seen histologically that indicates a diagnosis of alcoholic liver disease?
Neutrophils and fat accumulation within hepatocytes
What type of anaemia do you associate with alcoholic liver disease?
Macrocytic anaemia
What distinctive feature is often seen on biopsy in people suffering form alcoholic liver disease?
Mallory bodies
How do you treat alcoholic liver disease?
● Stop alcohol – treat delirium tremens with diazepam
● IV thiamine to prevent Wernicke-Korsakoff encephalopathy
● High vitamin and protein diet
● Fatty liver – if alcohol stopped fat disappears
● Hepatitis
o Nutrition maintained with enteral feeding and vitamin supplements
o Steroids show short term benefit – reduce inflammation
o Infections treated and prevented
● Cirrhosis
o Reduce salt intake, stop drinking for life
o Avoid aspirin and NSAIDS
o Liver transplant
How does alcoholic hepatitis present?
Jaundice Anorexia Nausea and vomiting Fever Encephalopathy Cirrhosis Hepatomegaly Ascites, bruising, clubbing
How long does hepatitis persist for to be deemed chronic?
6 months
Give 3 infective causes of acute hepatitis
- Hepatitis A-E infections
- EBV
- CMV
Give 3 non-infective causes of acute and chronic hepatitis
- Alcohol
- Drugs
- Toxins
- Autoimmune
Give 3 symptoms of acute hepatitis
- General malaise
- Myalgia
- GI upset
- Abdominal pain
- Raised AST, ALT
- +/- jaundice
If HAV a RNA or DNA virus?
RNA virus - PicoRNAvirus
How might you diagnose someone with HAV infection?
bloods - ALT/AST raised
raised IgG and IgM
Is HBV a RNA or DNA virus?
DNA virus Replicates in hepatocytes
Describe the natural history of HBV in 4 phases
- Immune tolerance phase
- unimpeded viral replication
- HBV DNA = high - Immune clearance phase:
- the immune system ‘wakes up’
- liver inflammation
- ALT = high - Inactive HBV carrier phase
- HBV DNA = low
- ALT levels = normal
- no liver inflammation - Reactivation phase
- ALT = intermittent
- HBV DNA = intermittent
- liver fibrosis
What HBV protein triggers the initial immune response?
The core proteins
Describe the management of HBV infection
vaccination pegylated interferon alpha 2a nucleotide analogue (tenofovir) - inhibits viral replications
How would you know if someone had acute or chronic HBV infection?
Follow up appointment at 6 months to see if HBsAg still present
still present = chronic hepatitis
What are the potential consequences of chronic HBV infection?
- Cirrhosis
- HCC
- Decompensated cirrhosis
Give 3 side effects of alpha interferon treatment for HBV
- Myalgia
- Malaise
- Lethargy
- Thyroiditis
- Mental health problems
Give 2 HBV specific symptoms
Arthralgia
Urticaria (hives)
If HCV a RNA or DNA virus?
RNA virus - flavivirus
How might you diagnose someone with current HCV infection?
HCV RNA - indicates current infection
Anti-HCV serology
Describe the treatment for HCV
Direct acting antivirals
NS5A inhibitor - Ritonavir
NS5B inhibitor - Sofosbuvir
Is HDV a RNA or DNA virus?
Incomplete RNA virus Needs Hep B for assembly
Is HEV a RNA or DNA virus?
Small RNA virus
Is HEV acute or chronic?
Usually acute but there is a risk of chronic disease in the immunocompromised
How might you diagnose someone with HEV infection?
HEV RNA - HEV IgM, IgGanti-HEV
Give 3 causes of non-alcoholic fatty liver disease
- T2DM
- Obesity
- Hypertension
- Hyperlipidaemia
How do you manage NAFLD?
Lose weight
Control HTN,
DM and lipids
What is Budd-Chiari syndrome?
Hepatic vein occlusion –> ischaemia and hepatocyte damage –> liver failure or insidious cirrhosis
Name 3 metabolic disorders that can cause liver disease
- Haemochromatosis - iron overload
- Alpha 1 anti-trypsin deficiency
- Wilson’s disease - disorder of copper metabolism
90% of people with haemochromatosis have a mutation in which gene?
HFE - chromosome 6
Haemochromatosis is a genetic disorder, how is it inherited?
Autosomal recessive inheritance
Give 4 signs of haemochromatosis
- Fatigue, arthralgia, weakness
- Hypogonadism – eg erectile dysfunction
- SLATE-GREY SKIN (brownish/bronze)
- Chronic liver disease, heart failure, arrythmias
How might you diagnose someone with haemochromatosis?
- bloods - Raised ferritin, LFTs
- HFE genotyping - C282Y
- Liver biopsy - gold standard
What is the treatment for haemochromatosis?
- Iron removal - venesection
- Monitor DM
- Low iron diet
- Screening for HFE
- iron-chelating drugs
Give 2 complications of haemochromatosis?
Liver cirrhosis –> failure/cancer
DM due to pancreatic depositions
How is alpha 1 anti-trypsin deficiency inherited?
Autosomal recessive mutation in serine protease inhibitor gene
Describe the pathophysiology of alpha 1 anti-trypsin deficiency?
● A mutation in the alpha-1-antitrypsin gene on chromosome 14 leads to reduced hepatic production of alpha-1-antitrypsin which normally inhibits the proteolytic enzyme, neutrophil elastase
● Deficiency results in emphysema, liver cirrhosis and hepatocellular carcinoma
How does Alpha 1 anti-trypsin deficiency present?
Liver disease in the young - cirrhosis, jaundice
Lung disease in the old (smokers) - emphysema
How would you diagnose Alpha 1 anti-trypsin deficiency?
Serum alpha-1-antitrypsin levels are low
What is the treatment for Alpha 1 anti-trypsin deficiency?
● No treatment
● Treat complications such as liver disease
● Stop smoking
● Those with hepatic decompensation should be assessed for liver transplant
● Manage emphysema
How does Wilson’s disease present?
Children = liver disease - hepatitis, cirrhosis, fulminant liver failure
Adults = CNS problems, mood changes, and Kayser-Fleischer rings
What CNS changes are seen in a patient with Wilson’s disease?
Tremor Dysarthria Dyskinesia Ataxia Parkinsonism Dementia Depression
What is the treatment for Wilson’s disease?
Lifetime treatment with penicillamine (chelating agent)
Low Cu diet - no liver, nuts, chocolate, mushrooms, shellfish
Liver transplant
Describe the pathophysiology of autoimmune hepatitis
Abnormal T cell function and autoantibodies vs hepatocyte surface antigens
What people are more likely to present with autoimmune hepatitis?
Young (10-30) and middle aged (>40) women
How does autoimmune hepatitis present?
Fatigue, fever, malaise Hepatitis Hepatosplenomegaly Amenorrhoea Polyarthritis Pleurisy Lung infiltrates Glomuleronephritis
What diseases are associated with autoimmune hepatitis?
Autoimmune thyroiditis DM Pernicious anaemia PSC UC
What results would you see from the investigations of someone who you suspect has autoimmune hepatitis?
Raised LFTs - increased bilirubin, AST, ALT, ALP
Hypersplenism = low WCC and platelets
Autoantibodies = +ve ANA
Liver biopsy = mononuclear infiltrate
How is autoimmune hepatitis treated?
Prednisolone - immunosuppression
Liver transplant
What is primary biliary cirrhosis?
An autoimmune disease where intra-hepatic bile ducts are destructed by chronic granulomatous inflammation –> cholestatis (bile in liver) –> cirrhosis, fibrosis, portal hypertension
Describe 2 features of the epidemiology of primary biliary cirrhosis
- Females > males
2. Familial - 10 fold risk increase
Give 3 disease associated with primary biliary cirrhosis
- Thyroiditis
- RA
- Coeliac disease
- Lung disease
Other autoimmune diseases
Give 3 symptoms of primary biliary cirrhosis
- Pruritis
- Fatigue
- Hepatosplenomegaly
- Obstructive jaundice
- Cirrhosis and coagulopathy
What would investigations show in someone with primary biliary cirrhosis?
Bloods = LFT - GGT and ALP raised
Positive anti-mitochondrial antibody (AMA) = diagnostic
low albumin
Liver biopsy = epithelial disruption and lymphocyte infiltration
What is the treatment for primary biliary cirrhosis?
early stage = Ursodeoxycholic acid + steroids + Cholestyramine
ADEK vitamins
severe = Liver transplant
What is Primary sclerosing cholangitis?
Autoimmune inflammation and narrowing of intra and extra hepatic bile ducts
Describe the pathophysiology of primary sclerosing cholangitis
Inflammation of the bile duct –> stricture and hardening –> progressive obliterating fibrosis of bile duct branches –> cirrhosis –> liver failure
Give 3 causes of primary sclerosing cholangitis
- Primary = unknown causes
- Infection
- Thrombosis
- Iatrogenic trauma
Give 3 symptoms of primary sclerosing cholangitis
- Pruritus
- Charcot’s triad = fever with chills, RUQ pain, obstructive jaundice
- Cirrhosis
- Liver failure
- Fatigue
What would the investigations show in someone with primary sclerosing cholangitis?
Bloods = high ALP, bilirubin, pANCA
AMA negative
Imaging = ERCP and MRCP
Liver biopsy = fibrous and obliterative cholangitis
What is the treatment for primary sclerosing cholangitis?
- Cholestyramine for pruritus
- Ursodeoxycholic acid - may protect against colon cancer and improve LFT
- ADEK vitamins
- Liver transplant
What complications might occur due to primary sclerosing cholangitis?
Increased risk of bile duct, gallbladder, liver and colon cancer
Give 3 causes of ascending cholangitis?
Gallstone
Primary infection (Klebsiella, E. coli)
Strictures following surgery
Pancreases head malignancy
What other symptoms can present with Charcot’s triad with ascending cholangitis?
Reynolds pentad
- Charcot’s triad (fever, RUQ pain, jaundice)
- Hypotension
- Confusion/altered mental state
What investigations might you do in someone who you suspect might have ascending cholangitis?
- USS
- Blood tests - LFTS
- CT - excludes carcinoma
- ERCP - definitive investigation
Describe the management of ascending cholangitis
Fluid resuscitation Treat infection with broad spectrum antibiotics (cefotaxime, metronidazole) ERCP to clear obstruction Stenting Laparoscopic cholecystectomy
What is the difference between the clinical presentation of ascending cholangitis and acute cholecystitis?
A patient with acute cholecystitis would not have signs of jaundice
What is the main difference between biliary colic and acute cholecystitis?
Acute cholecystitis has an inflammatory component
What complications can occur due to acute ascending cholangitis?
Sepsis Biliary colic Acute cholecystitis Empyema Carcinoma Pancreatitis
what are the different types of peritonitis?
- Primary = spontaneous bacterial peritonitis, ascites, immunocompromised
- Secondary = Bowel perforation, abdomen organ inflammation, TB, bowel ischaemia
Give 3 symptoms of peritonitis
- Abdominal pain and tenderness
- Nausea and vomiting
- Chills
- Rigors
- Fever
Give 3 signs of peritonitis on an abdomen examination
- Guarding
- Rebound tenderness
- Rigidity
- Silent abdomen
- lying still
What investigations might you do in someone who you suspect could have peritonitis?
- Blood tests: raised WCC, platelets, CRP, amylase, reduced blood count
- CXR: look for air under the diaphragm
- Abdominal x-ray: look for bowel obstruction
- CT: can show inflammation, ischaemia or cancer
- ECG: epigastric pain could be related to the heart
- B-HCG: a hormone secreted by pregnant ladies
What is the management for peritonitis?
- ABCDE
- Treat the underlying cause - might be surgery if perforated bowel
- IV fluids
- IV antibiotics - first broad spectrum then specific
- peritoneal lavage (clean the cavity surgically)
Give 5 potential complications of peritonitis
- Hypovolaemia
- Kidney failure
- Systemic sepsis
- Paralytic ileus
- Pulmonary atelectasis (lung collapse)
- Portal pyaemia (pus in portal vein)
What is the commonest serious infection in those with cirrhosis?
Spontaneous bacterial peritonitis
Name a bacteria that can cause spontaneous bacterial peritonitis
- E. coli
2. S. pneumoniae
How can spontaneous bacterial peritonitis be diagnosed
By looking for the presence of neutrophils in ascitic fluid
Describe the treatment for spontaneous bacterial peritonitis
Cefotaxime and metronidazole
What is acute pancreatitis?
An inflammatory process with release of inflammatory cytokines (TNF alpha, IL-6) and pancreatic enzymes (trypsin, lipase)
the pancreas returns to functionally and structurallynormal after the episode
Occurs as isolated or recurrent attacks
Describe the pathophysiology of acute pancreatitis
Main two causes are alcohol and gallstones:–
Gallstones:
Blockage of bile duct = backup of pancreatic juices. This change in luminal concentration causes Ca2+ release inside pancreatic cells and cause them to activate trypsinogen early which digests the pancreas.
Alcohol:
Contracts the Ampulla of Vater obstructing the bile clearance and also messes with Ca2+homeostasis causing the same as above.
• Leaky and damaged pancreas an auto digest nearby structures causing haemorrhage and Grey
Turner’s sign abdominal skin discolouration from retroperitoneal bleeding.
• Deranges pancreatic function so can cause hyperglycemia from reduction of insulin production
What are the causes of acute pancreatitis?
I GET SMASHED – remember I = Idiopathic G = Gallstones (60%) E = Ethanol = alcohol (30%) T = Trauma S = Steroids M = Mumps A = Autoimmune S = Scorpion venom H = Hyperlipidaemia/ hypothermia/ high Ca E = ERCP (endoscopic retrograde cholangiopancreatography) D = Drugs (furosemide, corticosteroid, NSAIDs, ACEi)
which drugs can cause acute pancreatitis?
furosemide,
corticosteroid,
NSAIDs,
ACEi
Give 4 symptoms of acute pancreatitis
- Severe epigastric pain that radiates to the back
- Anorexia
- Nausea, vomiting
- Signs of septic shock - fever, dehydration, hypotension, tachycardia
- Necrotising - umbilical (Cullens sign) vs flank (Grey Turners sign)
What investigations are done on someone you think has acute pancreatitis?
Raised serum amylase and lipase urinalysis - raised urinary amylase Erect CXR Contrast CT MRI
Describe the treatment for acute pancreatitis
- analgesia
- nil by mouth
- IV fluids
- prophylactic antibiotics
Give 2 potential complications of acute pancreatitis
- Systemic inflammatory response syndrome
- Multiple organ dysfunction
- Pancreatic necrosis
- hyperglycaemia
- hypocalcaemia
- renal failure
- shock
What is chronic pancreatitis?
Chronic inflammation of the pancreas leads to irreversible damage
- Progressive loss of exocrine pancreatic tissue which is replaced by fibrosis
Describe the pathogenesis of chronic pancreatitis
Pancreatic duct obstruction leads to activation of pancreatic enzymes –> necrosis –> fibrosis
Name 3 causes of chronic pancreatitis
- Excess alcohol - most common
- CKD
- Idiopathic
- Recurrent acute pancreatitis
- hereditary
- CF - all have it from birth
- autoimmune
- tropical
What is the clinical presentation of chronic pancreatitis?
- Severe epigastric pain that radiate through to the back - worse after alcohol/meal and better on leaning forward
- Weight loss, malabsorption
- Nausea, vomiting
- Steatorrhea (lack of lipase)
- Exocrine/endocrine dysfunction (DM)
- jaundice
A sign of chronic pancreatitis is exocrine dysfunction, what can be consequence of this?
- Malabsorption
- Weight loss
- Diarrhoea
- Steatorrhoea
A sign of chronic pancreatitis is endocrine dysfunction, what can be consequence of this?
DM
What immunoglobulin might be elevated in someone with autoimmune chronic pancreatitis?
IgG4
How is autoimmune chronic pancreatitis treated?
Steroids
What is the treatment for chronic pancreatitis?
Alcohol cessation
Analgesia (NSAIDs, tramadol)
Pancreatic enzyme (creon) and vitamin replacement
pancreatin + omeprazole
If DM = insulin
Surgery - local resection, for unremitting pain and duct draining
What 2 enzymes, if raised, suggest pancreatitis?
LDH (lactate dehydrogenase) and AST
Give 3 complications of chronic pancreatitis
- Diabetes
- Pseudocyst
- Biliary obstruction –> obstructive jaundice, cancer
Name a drug that can cause drug induced liver injury
- Co-amoxiclav
- Flucloxacillin
- Erythromycin
- TB drugs
Give 5 causes of diarrhoea infection
- Traveller’s diarrhoea
- Viral - (rotavirus/norovirus)
- Bacterial (E. coli)
- parasites (helminths, protozoa)
- Nosocomial (C. diff)
Give 5 causes of non-diarrhoeal infection
- Gastritis/peptic ulcer disease (H. pylori)
- Acute cholecystitis
- Peritonitis
- Thyphois/paratyphoid
- Amoebic liver abscess
Give 3 ways in which diarrhoea can be prevented
- Access to clean water
- Good sanitation
- Hand hygiene
What is the diagnostic criteria for travellers diarrhoea?
> 3 unformed stools per day and a least one of:
- abdominal pain
- cramps
- nausea
- vomiting
Occurs within 2 weeks (usually 3 days) of arrival in a new country
give 3 causes of travellers diarrhoea
- Enterotoxigenic E. coli
- Norovirus
- Giardia
Describe the pathophysiology of traveller’s diarrhoea
Heat labile ETEC modifies Gs and it is in a permanent ‘locked on’ state
Adenylate cyclase is activated and there is increased production of cAMP
Leads to increased secretion of Cl- into the intestinal lumen, H2O follows down as osmotic gradient –> diarrhoea
Which type of E. coli can cause bloody diarrhoea and has a shiga like toxin?
Enterohaemorrhagic E.coli (EHEC)
What is the leading cause of diarrhoea illness in young children?
Rotavirus
There is a vaccine = rotary
Give 5 symptoms of helminth infection
- Fever
- Eosinophilia
- Diarrhoea
- Cough
- Wheeze
Why is c. diff infectious?
Spore forming bacteria (gram positive)
Give 5 risk factors for c.diff infection
- Increasing age
- Comordities
- Antibiotic use
- PPI
- Long hospital admission
- NG tube feeding and GI surgery
- Immunocompromised - HIV, anti-caner drugs
Name 5 antibiotics that can cause c. diff infection
- Ciprofloxacin (quinolones)
- Co-amoxiclav (penicillins)
- Clindamycin
- Cephlosporins
- Carbapenems
RULE OF C’s
Describe the treatment for c. diff infection
VANCOMYCIN
Metronidazole and vancomycin (PO)
Rifampicin/rifaximin
Stool transplant
What can helicobacter pylori infections cause?
H. pylori produces urease –> ammonia –> damage to gastric mucosa –> neutrophil recruitment and inflammation
Causing gastritis, peptic ulcer disease, gastric cancer
Define biliary colic
Pain associated with the temporary obstruction of the cystic or common bile duct by a stone
what investigations should be undertaken for jaundice?
- liver enzymes - very high ALT/AST- MRCP or ERCP
- urine - bilirubin absent in pre-hepatic, in obstructive urobilinogen absent
- FBC
- ultrasound
what is the clinical presentation of biliary colic?
● Recurrent episodes of severe and persistent pain in the upper abdomen which subsides after several hours
● Pain may radiate to right shoulder and suprascapular region
● Vomiting
● Normal examination
what investigations should be undertaken for biliary colic?
● History and US showing gallstones
● Increases of serum alkaline phosphatase and bilirubin during an attack support the diagnosis of biliary pain
● Absence of inflammatory features differentiates this from acute cholecystitis
what is the management of biliary colic?
● Analgesics and elective cholecystectomy
● Abnormal liver biochemistry or a dilated CBD on US is an indication for preoperative MRCP
● CBD stone removed at ERCP
what is the clinical presentation of cholecystitis?
- Generalised epigastric pain migrating to severe RUQ pain.
- Signs of inflammation like a fever or fatigue.
- Pain associated with tenderness and guarding from inflamed gallbladder and local peritonitis.
Tenderness worse on inspiration (Murphy’s sign)
what are the investigations for cholecystitis?
- Positive Murphy’s Sign = Severe pain on deep inhalation with examiners hand pressed into the RUQ.
- Inflammatory markers - FBCs, CRP
- Ultrasound: Thick gallstone walls from inflammation
what is the management of cholecystitis?
• Antibiotics IV,
heavy analgesia,
IV fluids
an eventual Cholecystectomy if needed.
what is the pathophysiology of cholecystitis?
• Stone is blocking the ducts. Bile builds up, distending the gallbladder. Vascular supply may be reduced from this distension.
Inflammation follows these events secondary to the retained bile, inflaming the gall bladder.
what are the complications of cholecystitis?
● Empyema (pus)
● Perforation with peritonitis
what is the pathophysiology of primary biliary cholangitis (primary biliary cirrhosis)?
- Due to prolonged bile duct blockage, bile isn’t ‘flushing’ out the tubes so bacteria can climb up from the GI tract and cause biliary tree infection and consolidation.
- This prevents bile entering the GI tract and causes jaundice.
- 5-10% mortality and infection can affect the pancreas too since it shares ducts with the gallbladder.
what is the clinical presentation of primary biliary cholangitis (primary biliary cirrhosis)?
- Severe RUQ pain, with fever (rigors) AND jaundice.
* Patient may present as septic and/or have developed some level of pancreatitis.
what are the investigations for primary biliary cholangitis (primary biliary cirrhosis)?
POSITIVE AMA
Raised ALP and Bilirubin, raised CRP
• Blood cultures/MC&S
• Ultrasound +/- ERCP
what is primary biliary cholangitis?
also known as primary biliary cirrhosis
● Infection of the biliary tree
● Most often occurs secondary to CBD obstruction
what is ascending cholangitis?
bile duct infection, usually caused by bacteria ascending from its junction with the duodenum
what is the clinical presentation of ascending cholangitis?
RUQ pain, jaundice, & rigors (Charcot’s triad’)
what is the treatment for ascending cholangitis?
Cefuroxime IV & Metronidazole IV/PR.
what is primary sclerosing cholangitis?
a disease of the bile ducts that causes inflammation and obliterative fibrosis of bile ducts inside and/or outside of the liver.
- This pathological process impedes the flow of bile to the intestines and can ultimately lead to cirrhosis of the liver, liver failure, and bile duct and liver cancer
what are the pre-hepatic causes of portal hypertension?
portal vein thrombosis
what are the intrahepatic causes of portal hypertension?
- schistosomiasis
- cirrhosis
- budd-chiari syndrome
what are the post-hepatic causes of portal hypertension?
- RH failure
- IVC obstruction
what is the pathophysiology of portal hypertension?
- Increased resistance to blood flow leads to portal hypertension causes splanchnic vasodilation
- This results in a drop in BP
- CO increases to compensate for BP resulting in salt and water retention
- Hyperdynamic circulation/increased portal flow leads to the formation of collaterals between portal and systemic systems
what is the treatment of GI varices?
● fluid resuscitation until haemodynamically stable
● If anaemic – blood transfusion
● Correct clotting abnormalities – vitamin K and platelet transfusion
● Vasopressin – IV terlipressin or octreotide
● Prophylactic antibiotics
● Variceal banding
● Balloon tamponade
● TIPS
what is the clinical presentation of varices?
o Haematemesis o Abdominal pain o Shock o Fresh rectal bleeding o Hypotension and tachycardia o Pallor o Suspect varices as cause of GI bleeding if alcohol abuse or cirrhosis Splenomegaly and hyponatraemia
what is the prevention of varices?
o Nonselective B blockade – propranolol – reduced resting pulse and decrease portal pressure
o Variceal banding repeated to obliterate varices
o TIPSS
o Liver transplant
what are the risk factors for developing ascites?
- high sodium diet
- HCC
- splanchnic vein thrombosis causing portal hypertension
what are the causes of ascites?
● liver failure - cirrhosis ● Portal hypertension e.g. cirrhosis ● Hepatic outflow obstruction ● Budd-Chiari syndrome ● Peritonitis ● Pancreatitis ● Cardiac failure ● Constrictive pericarditis
what are the clinical features of ascites?
- large distended abdomen
- mild pain and discomfort
- shifting dullness - classic sign, percuss abdomen and observe dullness over fluid versus resonance over air. Ask the patient to roll on to one side, wait a good few seconds for fluid to settle at a new level then percuss on the side and observe the dullness has shifted.
what investigations should be done for ascites?
● Diagnostic aspiration of 10-20ml of ascitic fluid
o Raised white cell count indicates bacterial peritonitis
o Gram stain and culture
o Cytology for malignant cells
o Amylase to exclude pancreatic ascites
● Protein measurement of ascitic fluid
o Transudate (low protein) - Portal hypertension, constrictive pericarditis, cardiac failure, Budd-Chiari syndrome
o Exudate (high protein) BAD!! - Malignancy, peritonitis, pancreatitis, peritoneal tuberculosis, nephrotic syndrome
what is the management of ascites?
- treat underlying cause
- low sodium diet
- spironolactone and furosemide
- drain fluid - paracentesis
what can be a complication of ascites?
spontaneous bacterial peritonitis
what investigations are undertaken for chronic pancreatitis?
- serum amylase and lipase - may be raised
- abdominal US, CT and MRI
what is alpha 1 antitrypsin deficiency?
- rare cause of cirrhosis
- autosomal recessive condition
- mutation of alpha-1-antitrypsin gene on chromosome 14
what is the treatment for gallstones?
● Analgesics and elective cholecystectomy
● CBD stone removed at ERCP
what investigations are undertaken for gallstones?
FBC and CRP: Looking for signs of an inflammatory response - suggestive of cholecystitis
• LFTs: Raised ALP - Bilirubin and ALT usually normal.
• Amylase: Check for pancreatitis
• Ultrasound = diagnostic:
1.Stones
2.Gallbladder wall thickness (inflammation)
3.Duct dilation (suggests distal blockage)
what are the side-effects of chelating agents?
skin rash,
fall in WCC, HB and platelets,
haematuria,
renal damage
what are the investigations for wilsons disease?
- Serum copper and ceruloplasmin reduced (but can be normal)
- 24hr urinary copper excretion high
- Liver biopsy – diagnostic
what are the causes of peritonitis?
bacterial = most common
- gram -ve coliforms - e.coli
- gram +ve staphylococcus
chemical - bile, old clotted blood
what is the clinical presentation of HAV?
nausea,
anorexia,
distaste for cigarettes
some become jaundiced - dark urine and pale stool
what is the epidemiology of HEV?
● Common in Indochina
● More common in older men
● Commoner than Hep A in UK
● High mortality rate in pregnancy
what is the management of HEV?
● Prevention via good sanitation and hygiene, vaccine also available
● Once you’ve had it once you cannot become infected again
what are the test results for HBV?
● HBsAg is present 1-6 months after exposure
● HBsAg presence for more than 6 months implies carrier status
● Anti-HBs – antibodies
what are the clinical features of HDV?
similar to HBV
what are the investigations for HDV?
similar to HBV
HDV-RNA
anti-HDV
what is the treatment for HDV?
treat HBV
SC pegylated interferon-alpha-2a
what is the epidemiology of HCV?
● High incidence in Egypt due to failed public health initiative
● Transmitted by blood and blood products
● Very high incidence in IV drug users
● Limited sexual transmission
● Vertical transmission is rare
how do you remember the viral hepatitis information?
● A = Acquired by mouth from Anus, is Always cleared Acutely and only ever Appears once
● E = Even in England and can be Eaten (found in pigs), if not always beaten
● B is Blood-Borne and if not Beaten can be Bad
● B and D is DastarDly
● C is usually Chronic but Can be Cured at Cost
what are the risk factors for non-alcoholic fatty liver disease?
Obesity, diabetes, hyperlipidaemia, parental feeding, jejuno-ileal bypass, wilsons disease, drugs - Amiodarone, Tetracycline ,Methotrexate, Tetracycline
which drugs increase the risk of developing non-alcoholic fatty liver disease?
Amiodarone, Tetracycline ,Methotrexate
what are the clinical features of non-alcoholic fatty liver disease?
Usually no symptoms; liver ache in 10%
Fat, sometimes with inflammation & fibrosis
what are the investigations for non-alcoholic fatty liver disease?
Fat, sometimes with inflammation & fibrosis
Need biopsy to distinguish NAFL from NASH
what is the treatment for non-alcoholic fatty liver disease?
control risk factors, bariatric surgery - to treat obesity
what is the pathophysiology of fatty changes of the liver?
o Most common biopsy finding in alcoholic individuals
o Symptoms usually absent and on examination there may be hepatomegaly
o Lab tests often normal although elevated MCV indicates heavy drinking
o GGT level usually elevated
o Fat disappears on cessation of alcohol
what is the pathophysiology of alcoholic cirrhosis?
o Classically of the micronodular type but mixed pattern is also seen accompanying fatty change, and evidence of pre existing alcoholic hepatitis may be present
what are the clinical features of fatty liver?
o No symptoms or signs
o Vague abdominal symptoms are due to general effects of alcohol on the GI tract
what are the clinical features of alcoholic cirrhosis?
o Final stage of liver disease from alcohol
o Patients can be well with very few symptoms
o Usually signs of chronic liver disease
o Diagnosis confirmed by liver biopsy
o Features of alcohol dependency
what are the investigations for fatty liver?
o Elevated MCV indicates heavy drinking
o Raised ALT and AST
o Ultrasound or CT/liver histology will demonstrate fatty infiltration
what are the investigations for alcoholic hepatitis?
o FBC – leucocytosis, elevated MCV, thrombocytopenia
o Serum electrolytes abnormal – elevated serum creatinine
o Elevated AST, ALT, bilirubin, prothrombin time
o Microscopy and culture of blood, urine and ascites to search for infection
o Liver and biliary US used to identify obstruction
what is the management for alcoholic hepatitis?
o Nutrition maintained with enteral feeding and vitamin supplements
o Steroids show short term benefit – reduce inflammation
o Infections treated and prevented
what is the management for alcoholic cirrhosis?
o Reduce salt intake, stop drinking for life
o Avoid aspirin and NSAIDS
o Liver transplant
which condition is associated with primary sclerosing cholangitis?
IBD - especially ulcerative colitis
what do the following serological markers indicate in HBV infection?
- HBsAg
- HBeAg
- HBV-DNA
- anti-HBs
- anti-HBc IgM
- anti HBc IgG
- anti HBe
- HBsAg = acute infection (persistence after >6months implies chronic infection)
- HBeAg = acute infection (persistence implies active viral replication) - can distinguish between active and inactive chronic infection
- HBV-DNA = implies viral replication (present in acute and chronic)
- anti-HBs = immunity to HBV from immunisation or previous cleared infection
- anti-HBc = implies previous or current infection
- anti-HBc IgM = recent infection within last 6 months
- anti-HBc IgG = persists long term
- anti-HBe = seroconversion and is present for life
what do the following liver function tests indicate?
ALT, ALP, AST, GGT
ALT = liver specific ALP = bile duct specific AST = alcohol specific GGT = differentiate between bone and liver
what are the primary bile salts?
colic acid and chenodeoxycholic acid`
what are the secondary bile salts?
deoxycholic acid and lithocholic acid
how are primary bile salts turned into secondary bile salts?
Primary bile salts turn into secondary bile salts by dehydroxylation by bacteria in the gut
what are the investigations for NAFLD?
1st line
- enhanced liver fibrosis test (<7.7 = non-mild, >7.7-9.8 = moderate, >9.8 = severe)
- LFTs - increased AST and ALT (AST:ALT ratio close to 1)
- FBC - anaemia or thrombocytopenia
gold standard
- liver US (diffuse fatty infiltration and abnormal echotexture)
- liver biopsy (required for diagnosis)
how can you tell the difference between NAFLD and alcoholic liver disease?
AST:ALT ratio
ratio close to 1 = NAFLD
2:1 ratio = alcoholic liver disease
what are the symptoms of pre-hepatic jaundice?
pallor
fatigue
exertional dyspnoea
what are the symptoms of intra-hepatic jaundice?
anorexia
fatigue
nausea
abdominal pain
what are the symptoms of post-hepatic jaundice?
pale stools dark urine pruritus steatorrhea RUQ pain hepatomegaly
what conditions are associated with primary biliary cholangitis (primary biliary cirrhosis)?
IBD
what are the investigations for chronic pancreatitis?
Secretin stimulation test CT or MRI - pancreatic duct dilation, calcification, atrophy or pseudocysts endoscopic ultrasound Erect CXR fecal elastase test - decreased elastase
what cancer marker is present in hepatocellular carcinoma?
alpha-fetoprotein