Chronic Liver Disease, Cirrhosis, Gallstone problems Flashcards
Cirrhosis histology
Px: necrosis of hepatic parenchyma causes connective tissue proliferation and nodular regeneration
Acute liver failure causes:
Infection [3]
Toxins [4]
Other [3]
Obstetric [2]
Ischemic [1]
What is a trigger of cirrhosis and decompensated liver failure?
o Infection: hepatitis A or B, CMV, EBV, leptospirosis
o Toxins: alcohol, paracetamol, isoniazid, halothane
o Other: Budd-Chiari, Wilson’s, autoimmune hepatitis
o Obstetric: eclampsia, acute fatty liver of pregnancy
o Ischaemic hepatitis: post cardiac arrest
Cirrhosis can be triggered by constipation
Liver failure
Classic triad
Presentation [5]
• Classic triad: encephalopathy, jaundice, coagulopathy
- jaundice
- oedema and ascites
- bruising
- encephalopathy (asterixis and constructional apraxia (unable to draw 5-pointed star)
- fetor hepaticus
Investigation of liver failure [7]
- FBC: leucocytosis (infection), anaemia (GI bleed), reduced MCV (alcohol)
- U&E and creatinine: hepatorenal syndrome
- LFT
- ABG: metabolic acidosis
- Clotting: increased INR
- Glucose: hypoglycaemia (gluconeogenesis is the last function to fail)
- Underlying cause: liver screen incl. paracetamol screen
Mx of liver failure [3]
Monitoring [3]
ITU admission with mx of underlying cause
• Nutrition: via NGT with high carbs, PABRINEX
• Stress ulcer prevention: PPI
• Monitoring:
- fluid balance (urinary and CVP catheters)
- glucose (1-4hrly with 10% dextrose IV 1L/12h)
- bloods (daily FBC, U&E, LFT, INR)
Liver transplantation in acute failure
King’s college hospital criteria: PCM induced [4] and non-PCM induced [6]
o Paracetamol induced: - pH<7.3 24h after ingestion
- OR ALL 3 of
1. PT >100s
2. Cr >300mM
3. grade 3 or 4 encephalopathy
o Non-paracetamol induced:
- PT >100s
- OR 3 out of 5 of
1. drug induced
2. <10 or >40y/o
3. >1w from jaundice to encephalopathy
4, PT >50s
5. bilirubin >300uM
Managing cirrhosis [2]
- Prevent CX
- Laxatives
- Vitamin K
- Nutritional support
- Human albumin solution
- CIPRO - Liver transplant
What are cirrhosis complications? [4]
o Decompensation: hepatic failure
o Spontaneous bacterial peritonitis
o Portal hypertension: splenomegaly, ascites, varices, encephalopathy
o HCC: increased risk
Liver transplant indictions in non-acute liver failure [2]
Contraindicated [5]
Types [2]
Advanced cirrhosis
HCC
o CI: extra hepatic malignancy, severe cardiorespiratory disease, sepsis, HIV infection, non-compliance with therapy
o Types: cadaver (heart beating or heart not beating), live (right lobe)
Liver transplant mx post-op [2]
Complications [5]
12-24h in ITU
Immunosuppression
Complication:
- acute rejection 5-10d after, sepsis, hepatic artery thrombosis, chronic rejection, disease recurrence (HBV)
Hepatic encephalopathy
Pathophysiology [4]
- reduced hepatic metabolic function causes conversion of liver toxins directly into systemic system
- with ammonia accumulation and transfer over the BBB
- In the brain converted to glutamate and then glutamine
- causing osmotic imbalance and cerebral oedema
Hepatic encephalopathy Westhaven Classification [4]
Ix [3]
- I (confused): irritable, mild confusion, sleep inversion
- II (drowsy): increased disorientation, slurred speech, asterixis
- III (stupor): rousable, incoherent
- IV (coma): unarousable +/- extensor plantars
Ix: MOCA, ammonia (raised), EEG
Hepatic encephalopathy precipitants [4]
constipation haemorrhage
infection, electrolyte imbalance, hypoglycaemia,(hyponatraemia, hypokalaemia)
poisons (alcohol, diuretics, sedatives, anaesthetics)
HCC
Hepatic encephalopathy Mx [3]
Avoid sedation
Lactulose +/- phosphate enema
Rifaximin prophylaxis - reduces small bowel bacteria ammonia production
Portal hypertension pathophysiology [2[
- increased intrahepatic pressure causes increased hepatic portal pressure
- When this exceeds 12mmHg, collateral circulation form between portal and systemic circulation
Portal hypertension features [4]
- Oesophageal and gastric varices: portal long and short gastric veins anastomose with systemic inferior oesophageal veins
- Caput medusae: portal peri-umbilical veins anastomose with superior abdominal wall veins
- Prominent abdominal veins (more common): portal HTN if ABOVE umbilicus (IVC obstruction if below)
- Haemorrhoids: portal superior rectal veins anastomose with systemic middle and inferior rectal veins
Portal hypertension presentation [5]
- varices
- caput medusae
- haemorrhoids
- splenomegaly
- ascites, encephalopathy (NOT a cause of hepatomegaly)
Esophageal and gastric varices causes
Prehepatic
Hepatic [3]
Post hepatic [3]
- Pre-hepatic: portal vein thrombosis
- Hepatic: cirrhosis, schistosomiasis, sarcoidosis
- Post-hepatic: Budd-Chiari, RHF, constrictive pericarditis
Esophageal and gastric varices Pathophys
Px: portal HTN leads to dilated veins at sites of porto-systemic anastomosis (left gastric and inferior oesophageal veins)
Esophageal and gastric varices prevention [2]
o Non-cardio selective beta blocker: PROPRANALOL
o Endoscopic variceal band ligation (EVL): performed as PRIMARY GI BLEED PREVENTION at 2 weekly intervals until all varices eradicated (with PPI cover to prevent EVL induced ulceration)
Esophageal and gastric varices prophylactic or acute refractory management [5]
trans jugular intrahepatic Porto-systemic shunt (TIPSS)
- where IR used to create artificial channel between hepatic vein and portal vein
- to reduce portal pressure; involves using colapinto needle
- to create tract through liver parenchyma
- which is expanded using a balloon and maintained via stent placement
Hereditary haemochromotosis
Ep
Ax [2]
Px [3]
Ep: 40-60y/o
Ax: autosomal recessive mutation in HFE gene on chromosome 6
Px:
- inherited multisystem disorder due to abnormal iron metabolism
- where increased intestinal absorption (increased enterocyte DMT and reduced hepatocyte hepcidin)
- leading to deposition in multiple organs
Hereditary haemochromotosis - which organs can it affect? [6]
- Myocardial: dilated cardiomyopathy, arrythmias
- Endocrine: pancreas (DM), pituitary (hypogonadism causing amenorrhoea and infertility), parathyroid (hypocalcaemia, osteoporosis)
- Arthritis: 2nd and 3rd MCP joints, knees and shoulders
- Liver: chronic liver disease leading to cirrhosis and HCC, hepatomegaly
- Skin: slate grey/bronze discolouration
- Other: erectile dysfunction
Investigations for hereditary hemochromatosis [5]
- Bloods: LFT (ALT>AST), haematinics (increased ferritin and transferrin saturation (>55% in M and >50% in F) and iron and reduced total iron binding capacity)
- XR: chondrocalcinosis
- ECG and echo
- Liver biopsy: pearl stain to quantify Fe and severity
- MRI: estimates iron loading
Wilson’s disease
Ep
Ax
Px [3]
Ep: presents between childhood and 30y/o (NEVER >56y/o)
Ax: autosomal recessive mutation in ATP7B gene on chromosome 13
Px:
- mutation in copper transporting ATPase
- means there is impaired hepatocyte incorporation into caeruloplasmin and excretion into bile
- which results in copper accumulation in liver and later in other organs
Presentation: Wilson's disease Eyes Neurology Psychiatry Haematology
- Eyes: corneal Kayser Fleischer rings (may require slit lamp to see)
- Neurology: parkinsonism, spasticity, dysarthria, dysphagia, ataxia, asterixis
- Psychiatry: depression, dementia, psychosis
- Haematology: Coombs’ negative haemolytic anaemia
Presentation: Wilson's disease Liver [2] Renal [2] Gynae MSK [2]
- Liver: childhood acute hepatitis, fulminant necrosis may occur leading to cirrhosis
- Renal: renal tubular acidosis causing osteomalacia
- Gynae: recurrent miscarriage
- Arthritis: chondrocalcinosis and osteoporosis
What is type 1 hepatorenal
<2 weeks
Usually following acute event e.g. acute GI bleed
What is type 2 hepatorenal
Gradual decline in renal function
Usually in combination with refractory ascites
Define jaundice [2]
Clinical significant level of serum bilirubin [2]
Jaundice is yellowish discoloration of the sclera and mucous membrane
It is clinically manifest when serum bilirubin > 3mg/dL (51 µmol/L)
How can we classify jaundice [3]
Haemolytic jaundice
Hepatocellular jaundice
Obstructive jaundice
How can obstructive jaundice be classified further and differentiate between the two [4]
Medical obstructive jaundice
- Which is caused by intrahepatic biliary obstruction
Surgical obstructive jaundice
- Which is caused by extrahepatic biliary obstruction
Classify surgical obstructive jaundice into 2 groups
Calcular obstructive jaundice
Malignant obstructive jaundice
Haemolytic jaundice
Unconjugated bilirubin high
ALT, AST, ALP normal
Urine and stool normal
Hepatic jaundice
Mixed bilirubin
ALT+ AST high
ALP mild increase
Dark urine
Obstructive jaundice
Conjugated bilirubin raised
ALT and AST mild increase
ALP marked increase
Urine dark / pale stool
What are pre-hepatic causes of Jaundice [4]
Haemolysis
Gilbert, Crigler Naajar
Post-transfusion
Drugs
What are causes of hepatic [6]
All hepatomegaly causes
Drugs, TPN
3 C’s
Cancer, Cirrhosis, Congestion
3 I’s
Infection, Inflammation, Infiltration
What are obstructive causes [6]
CBD stone, Cholangitis
Cholangiocarcinoma
Stricture (iatrogenic)
Pancreatic cancer, Liver mets
PBC
Mirizzi syndrome
Cholelithiasis classification [3]
Types of stones
- Cholesterol gallstones 90%
- Bile pigment stones
- Mixed gallstones
Cholelithiasis pathogenesis: 2 mechanisms
What are risk factors of cholesterol gallstones [5]
Biliary colic
Acute cholecystitis
RF:
- Female
- Fat
- Forty
- Fertile
- Fair (genetic)
Cholelithiasis pathogenesis: difference between biliary colic and acute cholecystitis [5]
- Biliary colic: transient obstruction of cystic duct
- Acute cholecystitis:
- persistent cystic duct obstruction traps bile in the gallbladder
- causing irritation and increasing pressure
- trauma by gallstone stimulates prostaglandin release
- inflammation and secondary bacterial infection causing necrosis and perforation (occasionally acalculous)
Cholelithiasis presentation
Biliary colic [4]
Acute cholecystitis [4]
Biliary colic
- RUQ or epigastric pain
- 30min to 6h
- Sudden, dull, colicky
- Worse after meal, fatty foods
Acute cholecystitis
- Intense RUQ pain
- Initially in epigastrium and LLQ, referred to shoulder tip
- Previous episodes of biliary colic
- Fever, nausea, vomiting
Cholelithiasis presentation
Signs of acute cholecystitis
Paplable distended gallbladder
Pyrexia
Positive Murphy’s sign
What s Murphys sign? [3]
- palpation of the right subcostal region
- produces tenderness which worsens during deep inspiration and causes termination of inspiration
- only +ve if does not occur on LHS; can also be elicited during USS
- Indicates acute cholecystitis
Investigations cholelithiasis [3]
- Bloods: FBC (WCC up), CRP, amylase (?pancreatitis), LFT showing obstructive picture
- Abdo USS
- MRCP
Management of biliary colic [3]
NSAIDs, opiates as required
Anti-emetic
Elective laparoscopic cholecystectomy
within 6w of first presentation
Mx acute cholecystitis [4]
NBM, IV fluids, monitoring, analgesia, anti-emetic
IV abx - coamoxiclav, metronidazole
Laparoscopic cholecystectomy within 1 week
Percutaneous cholecystectomy
Window period to do an elective lap. chole. if biliary colic only
Window period to do an lap. chole. if acute cholecystitis
Elective lap chole:
Do within 6w of first presentation
Lap chole for acute cholecystitis:
- within 72h-1w of presentation
Complications of cholelithiasis
Gallbladder empyema
Mirizzi syndrome
Acute pancreatitis
Bouveret syndrome
Gallstone ileus
Mirizzi syndrome [2]
Gall stone impaction in neck of gallbladder
Causes compression of common bile duct and obstruction jaundice
Choledocholithiasis
Epidemiology [2]
Define
Sequelae
F>M, >40yo
Common bile duct stones
Can lead to ascending cholangitis
Choledocholithiasis presentation
Symptoms [2]
Signs [4]
Symptoms
- Fluctuating obstructive jaundice
- dark brown urine, pale stools)
- NO weight loss
Signs
- Pale lemon to bright orange jaundice
- Scratch marks
- Bradycardia
- Gallbladder not distended
Choledocholithiasis presentation: ascending cholangitis [2]
Charcots triad
Reynolds pentand
Describe charcots triad
Describe Reynolds pentand
o Charcot’s triad: RUQ pain, jaundice, fever/rigors
o Reynold’s pentand: Charcots triad + hypotension and confusion
Ix cholelithiasis
LFT
CRP, ESR (up)
Abdo USS
MRCP
Pancreatico-billiary EUS
Mx choledocholithiasis
- IV antibiotics
- ERCP after 24-48h: Endoscopic sphincterotomy + CBD stone extraction
- Laparoscopic cholecystectomy
Benign strictures causing obstructive jaundice:
Describe a typical patient [2]
Ix
Mx
- Typical pt: post-op jaundice if complete, intermittent cholangitis with jaundice if incomplete
- Ix: MRCP
- Mx: biliary stent or Roux-en-Y pancreatojejunostomy
Cholelithiasis vs choledolithiasis
Cholelithiasis is the presence of gallstones. Choledocholithiasis refers to the presence of one or more gallstones in the common bile duct (CBD).
Cholangiocarinoma Define Ep [4] Symptoms [4] Signs [3]
Bile duct and gallbladder cancer
Ep: Eastern Europe, Thailand, Japan and Korea
Symptoms: obstructive jaundice, abdominal pain, weight loss, anorexia
Signs:
- Courvoisiers sign
- Sister Mary Joseph nodes
- Virchow node
What is courvoisier’s sign?
Palpable painless RUQ mass most likely malignancy in biliary tree
- unlikely to be gallstones because gall stones are formed over a longer period of time, and this results in a shrunken, fibrotic gall bladder which does not distend easily
Describe Sister Mary Joseph nodes
Periumbilical lymphadenopathy
Cholangiocarcinoma
What type of cancer is it?
Risk factor?
Investigation [3]
Adenocarcinoma RF: primary sclerosing cholangitis 1. Abdo USS 2. CT 3. MRCP
Name the 3 biomarkers elevated in cholangiocarcinoma
CA-19-9, CEA, CA125
Mx cholangiocarcinoma [2]
Surgical resection is only curative option
But 80% have inoperable disease so:
- palliate w/ biliary stents or chemo
Malignant causes of surgical obstructive jaundice [3]
Cholangiocarcinoma
Pancreatic ca - head
Periampullary tumour
Primary sclerosing cholangitis (PSC)
Ax is unknown, what is PSC associated with?
Pathogenesis [2]
Associations:
- HLA-A1, B8 and DR3, autoimmune hepatitis, HIV
- Ulcerative colitis: affecting whole colon, IBD often presenting before PSC, although colitis is usually inactive, colorectal malignancy risk much increased
Patho: progressive cholestasis and intra and extrahepatic bile duct inflammation and strictures
PSC presentation [5]
Pruritus Fatigue RUQ pain Ascending cholangitis End stage hepatic failure (severe cases)
PSC Ix
LFT (bilirubin up, ALP up)
Autoab: hypergammaglobulinemia
MRCP (beaded appearance, strictures)
Liver biopsy (onion skin)
PSC Ix: describe what autoabs are positive [5]
hypergammaglobulinaemia, AMA NEGATIVE but ANA, SMA and ANCA may be +ve
Mx PSC
Medical [2]
Surgical
Monitoring [3]
- Medical: LOW dose UROSEOXYCHOLIC ACID (may improve LFTs and protect against colon cancer), CHOLESTYRAMINE for pruritus
- Transplant: for end stage disease (recurrence in 30%; worse prognosis if IBD as 30% develop colorectal cancer post-transplant)
- Monitoring: annual colonoscopy and USS, cholecystectomy for gallbladder polyps (usually incidental finding on USS and can be left if <1cm but a lot more likely to be malignant in PSC)
Complications of PSC [3]
bile duct, gallbladder, liver and colon cancers
Ascites
Ascites is defined as the presence of free fluid within the abdomen; in chronic liver disease it develops due to presinusoidal portal hypertension and is associated with:
* Changes in vascular tone: general vasodilatation, raised NO levels.
* Sodium retention (and, therefore, water) due to secondary hyperaldosteronism.
* Decreased ability to excrete free water due to increased antidiuretic hormone (ADH).
Ascites
Presentation, examination
Investigations
Presentation is either symptomatic (e.g. abdominal distension, breathlessness due to diaphragmatic splinting) or as an incidental finding on ultrasound. On examination, shifting dullness (>–.5L ascites) or a fluid thrill (tense ascites) may be detectable.
Key investigations when assessing ascites are:
* Abdominal ultrasound with Dopplers to quantify volume, identify appearances of chronic liver disease and portal hypertension, and exclude portal vein thrombosis.
* Fluid should be sampled (tapped) and analysed for WCC to exclude spontaneous bacterial peritonitis (SBP), Gram stain, bacterial culture, and albumin and total protein levels. Fluid LDH, amylase, lipids and cytology may be sent dependent upon appearance and putative causes.
* Calculate serum albumin ascites gradient (SAAG). SAAG = ascitic fluid [albumin] – serum [albumin]; if ≥1.1 g/L suggests ascites secondary to portal hypertension
Interpretation of Serum albumin ascites gradient (SAAG)
Treatment of ascites
The treatment of ascites includes:
* Sodium (<90 mmol/day) and fluid restriction (<1.5 L/day).
* Diuretics: spironolactone (initially 00 mg/day, but up to 400 mg/day), furosemide may be added.
Treatment should target gradual weight loss of 0.5 kg/day (i.e. 500 mL) and patients must be monitored for complications of therapy (hyponatraemia, hyperkalaemia and renal dysfunction). Failure to respond to or inability to tolerate diuretic therapy should trigger consideration of liver transplantation or TIPSS.
Spontaneous bacterial peritonitis
Aetiology [2]
Presentation
Diagnosis
Patients with ascites may develop the complication of SBP due to translocation of bowel organisms into ascites, leading to infection of the fluid.
Causative organisms are typically bowel flora (e.g. E. coli, Klebsiella sp.), though streptococcal and staphylococcal infections may occur.
Fever, abdominal tenderness and an altered mental state
SBP must be considered in any patient with ascites with a deterioration in liver function tests.
Patients with a low ascitic fluid albumin are at highest risk.
Diagnosis is based upon an ascitic fluid WCC >250/mm3 with >50% neutrophils.
Management of SBP [4]
Empirical broad-spectrum antibiotics (e.g. piperacillin-tazobactam, ciprofloxacin), after appropriate cultures have been sent.
* Renal failure and hepatorenal syndrome (HRS) may develop. Early plasma expansion with human albumin solution (HAS) reduces the risk, if this fails IV terlipressin is used.
* Recurrence of SBP approaches 70%, patients surviving an episode should receive antibiotic prophylaxis (lifelong or until liver transplantation).
* A single episode confers a poor prognosis and should prompt consideration of transplantation.
