Liver and friends Flashcards
1
Q
What are the 2 main types of cholangitis?
A
- Ascending cholangitis (Otherwise known as acute cholangitis).
- Primary sclerosing cholangitis.
- NOTE: there can be overlap between them.
2
Q
What is ascending cholangitis?
A
- Otherwise known as acute cholangitis.
- Acute infection of the biliary tree usually due to an obstruction.
- Strongly associated with Charcot’s triad.
3
Q
What are the symptoms of ascending cholangitis?
A
Charcot’s triad:
- RUQ pain
- Jaundice
- Fever
If severe:
- Changed mental status.
- Hypotension.
4
Q
What are the risk factors for ascending cholangitis?
A
- > 50 YO
- Cholelithiasis.
- Benign/malignant stricture in CBD.
- Sclerosing cholangitis.
5
Q
What is the pathophysiology of ascending cholangitis?
A
- Obstruction of the CBD.
- Bacterial seeding of the biliary tree.
- When acute infection occurs (usually E. coli), this can result in ascending cholangitis.
6
Q
What is the pathophysiology of SEPTIC ascending cholangitis?
A
- As the CBD blockage progresses, the pressure in the CBD increases.
- This can lead to extravasation of the bacteria, causing sepsis.
7
Q
What are the investigations used for ascending cholangitis?
A
- LFTs. Hyperbilirubinaemia. Raised ALP and usually raised GGT.
- CRP. Raised (acute inflammation).
- FBC. Raised WCC.
- Blood culture: Positive (usually E. coli).
IF SEVERE DISEASE:
- ABG. Metabolic acidosis and raised lactate.
- Creatinine/urea. Raised due to renal disease.
8
Q
What is the treatment for ascending cholangitis?
A
- ERCP. Reduces biliary pressure.
- Cerufoxime (cephalosporin) + metronidazole (antimicrobial).
- Strong analgesia (morphine + paracetamol).
IF SEPTIC, SEPSIS 6.
9
Q
What are the differentials for ascending cholangitis?
A
- Cholecystitis. Will have a +ve murphys sign (pain in RUQ on palpation during inspiration). Will also NOT have jaundice.
- Primary sclerosing cholangitis. NOT FINISHED YET.
10
Q
What is the most common bacterial cause of ascending cholangitis?
A
- E. Coli (gram -ve bacteria).
11
Q
What is the main complication of ascending cholangitis?
A
- Pancreatitis.
- If common bile duct obstruction is very distal, the pancreatic duct is also obstructed, which causes acute pancreatitis.
12
Q
What is the treatment for ascending cholangitis?
A
1st line:
- Fluid resuscitation.
- Potentially oxygen required.
- Antibiotic therapy (to clear the infection) Give IV until adequate biliary drainage has been achieved.
- Clear the obstruction (e.g. the gall stone) using ERCP.
13
Q
What is the treatment for sclerosing cholangitis?
A
MANAGE THE SYMPTOMS OF DECREASED LIVER FUNCTION:
- Rifampicin to reduce itching (puritis).
- Ca2+ and Vit. D supplementation for osteopenia.
- Immunosuppression if autoimmune hepatitis.
- ERCP can be used to dilate the strictures.
WHEN END-STAGE LIVER DISEASE/LIVER FAILURE REACHED:
- Liver transplant.
14
Q
What are the potential complications of ascending cholangitis?
A
- Sepsis is the main potential complication, due to the infection progressing.
15
Q
What are the components of a LFT and what do they mean?
A
- ALT is found in high concentrations in the hepatocytes, and enters the blood following HEPATOCELLULAR INJURY.
- ALP synthesis is increased following CHOLESTASIS (inability of bile to flow into the duodenum) AND BONE BREAKDOWN.
- GGT is also raised in response to BILE FLOW OBSTRUCTION OR HEAVY ALCOHOL USE.
- If ALP is raised and GGT is normal, suggests non-hepatobiliary pathology (e.g. vitamin D defficiency or bone fractures)
- Hyperbilirubinaemia doesn’t always cause jaundice. The stool and urine help identify the cause:
- Normal urine + normal stool = pre-hepatic cause
- Dark urine + normal stool = hepatic cause
- Dark urine + pale stool = post-hepatic cause.
- AST>ALT indicates cirrhosis and acute alcoholic hepatitis.
- ALT>AST indicates chronic liver disease.
16
Q
What is acute liver failure?
A
Rapid decline in hepatic function characterised by jaundice, encephalopathy and INR>1.5.
17
Q
What is the clinical presentation of acute liver failure?
A
- Hepatic encephalopathy.
- Jaundice.
- Abdominal pain.
- Nausea/vomiting.
18
Q
What are the risk factors for acute liver failure?
A
- Female
- > 40 YO
- Chronic alcohol abuse
- Hep B
- Use of hepatotoxic drugs
- Overdose of paracetamol.
19
Q
What is the generalised pathophysiology of acute liver failure?
A
Generally, it is the massive necrosis of hepatocytes, leading to liver failure.
20
Q
What is the pathophysiology of paracetamol overdose liver failure?
A
For paracetamol overdose:
- Normally, paracetamol is metabolised by CYP450 enzymes into NAPQ1.
- NAPQ1 is toxic, and so is then conjugated by glutathione (an antioxidant) to deem it safe.
- In paracetamol overdose, glutathione stores are depleted, leading to NAPQ1 not being conjugated. This causes hepatocellular injury and acute liver failure.
21
Q
How is acute liver failure investigated and what are the results?
A
- Assess for encephalopathy (Babinski reflex, asterixis, general awareness assessment etc.).
- INR measurement > 1.5 (indicative of extrinsic coagulopathy).
- LFT’s. Hyperbilirubinemia, VERY high AST/ALT, SLIGHTLY high ALP.
- Amylase/lipase - check for pancreatitis (a common complication of acute liver disease).
FOR PARACETAMOL OVERDOSE:
- Creatinine/urea. Check for renal failure.
- Paracetamol levels in blood.
- ABG (check for metabolic acidosis).
- Lactate.
22
Q
What is the treatment for acute liver failure?
What is the specific treatment for acute liver failure due to paracetamol overdose?
A
As soon as encephalopathy develops:
- ICU admission. Bed 30 degrees (for ICP management) and intubate (to secure the airway).
- Use propofol/fentanyl for analgesia (short half life).
- Give fluids (carefully monitor BP). Can be given containing glucose if patient is hypoglycaemic.
CONSIDER ALL ACUTE LIVER FAILURE PATIENTS FOR TRANSPLANT.
FOR PARACETAMOL OVERDOSE:
- Acetylcysteine.
23
Q
What is acute pancreatitis?
What is the diagnostic criteria?
A
- Inflammation of the pancreas with acinar cell injury.
Diagnostic criteria - must have at least 2/3 of the following:
- Severe epigastric/ lower back pain.
- Raised amylase or lipase.
- Suggestive findings on imaging.
24
Q
What are the two different types of pancreatitis?
A
- Acute
- Chronic
25
What is the clinical presentation of acute pancreatitis?
- Epigastric/ upper GI pain that radiates through to the back. (Sudden onset).
- Nausea/vomiting.
- Potentially hypovolaemia.
26
What is the pathophysiology of acute pancreatitis?
- Mechanism poorly understood.
- Intracellular Ca2+ accumulates.
- Direct insult to acinar cells.
- Intrapancreatic enzyme activation.
- Generalised inflammation.
27
What are the risk factors for/ causes of acute pancreatitis?
Remember this as I GET SMASHED:
- Idiopathic
- Gallstones
- Ethanol (alcohol)
- Trauma
- Steroids
- Mumps
- Autoimmune
- Scorpion stings
- Hyperlipidaemia/hypercalcaemia
- ERCP
- Drugs
28
What are the investigations used in acute pancreatitis?
Diagnostic investigations:
- Lipase (1st line) and amylase (2nd line) - raised.
- Imaging not normally needed.
OTHER:
- CRP raised.
- Raised haematocrit/urea/creatinine is indicative of hypovolaemia.
- After diagnosis, RUQ USS should be done to check for biliary pathology.
29
What is the treatment for acute pancreatitis?
- Hartmann's solution.
- Analgesia PRN (Ibuprofen, codeine, morphine).
- Ondansetron (anti-emetic).
If the patient has gall stones but no cholangitis:
- Cholecystectomy.
If patient has gall stones AND cholangitis:
- Emergency ERCP.
30
What are the potential complications of acute pancreatitis?
- Renal failure (AKI) due to hypovolaemia.
31
What is chronic pancreatitis?
Progressive injury to the pancreas, resulting in scarring and permanent loss of function.
32
What is the clinical presentation of chronic pancreatits?
- Dull epigastric pain, radiating to the back. Pain gets better with leaning forwards. Can be classified using the Ammann classification:
- Type A. Short, remitting episodes of pain.
- Type B. Longer, constant episodes of pain.
- Steatorrhoea.
- Weight loss (due to pain on eating).
33
What is the pathophysiology of chronic pancreatitis?
- Poorly understood.
| - Main cause is chronic alcohol abuse (70-80% of cases).
34
What are the risk factors for chronic pancreatitis?
- ALCOHOL IS THE MAIN RISK FACTOR.
- FH
- Coeliac disease.
35
What are the investigations used to diagnose chronic pancreatitis?
- CT or MRI abdomen is 1st line. Look for signs such as enlarged pancreas, calcifications etc.
- Gold standard. Pancreatic biopsy + histology. Look for acinar damage, fibrosis, increased connective tissue etc. (generally only used in high risk patients where imaging was inconclusive).
- Consider use of genetic testing in younger patients.
36
What is the treatment for chronic pancreatitis?
- Stop alcohol intake and stop smoking (1st line)
- Analgesia. Paracetamol or NSAIDs (1st line)
- Pancreatic enzyme replacement therapy - pancreatin (1st line) + omeprazole (PPI) so the enzymes can function better.
- ERCP drainage if there is biliary involvement.
37
What is the main potential complication of chronic pancreatitis?
- Diabetes due to reduced insulin secretion (called type 3c diabetes).
38
What is alcoholic liver disease?
Chronic liver disease caused by chronic heavy alcohol consumption.
39
What is the clinical presentation of alcoholic liver disease?
- PROLONGED HIGH ALCOHOL CONSUMPTION.
- RUQ pain.
- Hepatomegaly.
When more severe:
- Asterixis/confusion (hepatic encephalopathy).
- Jaundice
- Splenomegaly
40
What are the three main stages of alcoholic liver disease?
- Alcoholic fatty liver.
- Alcoholic hepatitis.
- Alcoholic liver cirrhosis.
41
What is the pathophysiology of alcoholic fatty liver disease?
Alcohol is normally metabolised through two main enzymes:
- CYP450
- Alcohol dehydrogenase
If the there is sustained high alcohol intake, strain is put on these pathways leading to:
- Increased free radicals in the liver.
- Increased fatty infiltration of hepatocytes.
Also, high alcohol intake leads to recruitment of hepatic macrophages, which secrete TNF-a and further amplify inflammatory processes.
All of these pathological processes result in cirrhosis, inflammation and hepatocyte necrosis in the liver.
42
What characteristic cells are found histologically in people suffering with alcoholic liver disease?
- Mallory bodies. Especially seen in the later stages (alcoholic hepatits, alcoholic liver cirrhosis).
43
What are the risk factors for alcoholic liver disease?
- Excessive, prolonged alcohol consumption MAIN ONE.
- Hep C - makes ALD more severe/progressive.
- Female (easier to get as a female, yet more prevalent in men).
44
What is the pathophysiology of alcoholic liver disease?
45
What is the epidemiology of alcoholic liver disease?
- Most common cause of chronic liver disease.
| - Usually presents in men
46
What investigations are conducted to diagnose alcoholic liver disease?
CAGE/AUDIT questionnaire:
- Used to assess alcohol intake/dependancy.
LFTs (liver function tests):
- AST and ALT both rise, but AST more so.
- Low albumin
- Raised bilirubin (both conjugated and unconjugated).
- In very severe alcoholic liver disease (cirrhosis) AST and ALT may be normal due to extreme levels of necrosis.
Hepatic USS - GS AND FIRST LINE.
- Look for hepatomegaly and cirrhosis.
- Should be carried out every 6-12 months for those with liver cirrhosis to screen for hepatocellular carcinoma.
47
What is the treatment for alcoholic liver disease?
- Alcohol abstinence and smoking cessation.
- Weight loss.
- Corticosteroids (prednisolone) to control inflammation if there is no renal failure.
- Consider loop diuretics (furesomide) for ascites.
- LIVER TRANSPLANT IN THE CASE OF ADVANCED ALCOHOLIC LIVER DISEASE (CIRRHOSIS).
48
What is primary sclerosing cholangitis?
- Chronic inflammation of the extra and/or intrahepatic ducts, leading to fibrosis and stricture.
49
What is the clinical presentation of primary sclerosing cholangitis?
Usually asymptomatic in early stages.
Can cause:
- Pruritus
- Jaundice
- RUQ pain
- NO FEVER (unless infection occurring too).
50
What are the risk factors for primary sclerosing cholangitis?
- Male (2:1)
- History of IBD (especially UC).
- FH (first degree relative).
51
What is the pathophysiology of primary sclerosing cholangitis?
- Chronic inflammation of/ injury to the biliary ducts leads to fibrosis and stricture.
- This causes cholestasis in the ducts, which increases the risk of cholelithiasis and infection.
- If prolonged, can cause liver cirrhosis and parenchymal damage, causing end-stage liver disease.
52
What are the investigations used for primary sclerosing cholangitis?
- LFTs. Extremely high ALP and GTT. Slightly/moderately raised AST/ALT (pattern indicative of cholestatic disease). Hyperbilirubinaemia is sustained in more advanced disease.
- MRCP (1st line) and ERCP (2nd line). Look for strictures.
53
What is the treatment given for primary sclerosing cholangitis?
If asymptomatic:
- Monitor and wait.
- Lifestyle advice (stop drinking and increase exercise).
If symptomatic:
- ERCP + balloon dilatation. Give ciprofloxacin prophylactically due to high infection risk.
When end-stage liver disease:
- Liver transplant (if possible).
54
What are the common complications of primary sclerosing cholangitis?
- End-stage liver disease
- Osteoporosis
- Hepatocellular carcinoma/cholangiocarcinoma.
55
What are the potential differentials for primary sclerosing cholangitis?
- Secondary sclerosing cholangitis. Will have an identifiable primary cause (e.g. recurrent pancreatitis).
- Autoimmune hepatitis. Will have a hepatic LFT pattern (Very high AST/ALT, slightly high ALP/GGT) and potentially raised IgG and ANA.
56
What is cholecystitis?
- Acute inflammation of the gall bladder, usually caused by gallstones (90%).
57
What is the clinical presentation of cholecystitis?
- RUQ pain
- +ve murphy's sign
- Fever
- Potentially a palpable gall bladder.
USUALLY NO JAUNDICE - DISEASE OF GALLBLADDER NOT LIVER.
58
What are the risk factors for cholecystitis?
- Gall stones.
- Diabetes.
- Nil by mouth (fasting or IV nutrition, as this will decrease gall bladder motility).
59
What is the pathophysiology of cholecystitits?
- Blockage of the cystic duct/neck of the gallbladder leads to cholestasis.
- Bile builds up in the gallbladder, increasing pressure and causing irritation.
- Triggers release of prostaglandins, which mediate inflammation in the gallbladder wall.
- In extreme cases, this can cause perforation/necrosis of the gallbladder.
60
What are the investigations used for cholecystitis?
- USS abdomen. Will show thickened gallbladder wall.
| - If septic: CT/MRI to find the source of the infection. Blood culture to assess antibiotic sensitivity.
61
What is the treatment for cholecystitis?
- Analgesia (paracetamol or morphine as appropriate).
- IV fluids until can tolerate oral intake.
- Laproscopic cystectomy EARLY AS POSSIBLE (with prophylactic antibiotics to reduce risk of infection).
62
What are the differentials for cholecystisis?
- Peptic ulcers. Usually pain will be more epigastric and associated with food intake.
- Ascending cholangitis (or acute cholangitis). Will have Jaundice (charcot's triad) which is absent in cholecystitis.
63
What are the main complications of cholecystitis?
- Gall bladder perforation.
| - Surgical damage to the cystic duct during laproscopic cholecystectomy.
64
What is cholelithiasis?
- Gall stones. Usually made of cholesterol, and can be in the gall bladder, cystic duct, common bile duct or pancreatic duct.
65
What are the clinical symptoms of cholelithiasis?
Usually asymptomatic until obstruction occurs. Then:
- Biliary colic pain
- Often associated with eating (cholecystic movement).
- If CBD obstruction present, may cause jaundice.
66
What are the risk factors for cholelithiasis?
- Age (peak at 70)
- Female (3:1)
- Nil by mouth (fasting/IV nutrition) as this causes gallbladder hypomobility.
- Diabetes/obesity (these cause increased cholesterol).
- FH.
67
What is the pathophysiology of cholelithiasis?
- 90% of gallstones are made of cholesterol.
| - Asymptomatic until they cause obstruction.
68
What is the pathophysiology Mirizzi syndrome?
- Gall stones become trapped in the gallbladder neck/cystic duct and put pressure through the wall onto the CBD/CHD. This causes jaundice too.
69
What is the pathophysiology of Bouveret syndrone?
- Gallstone erodes the wall of the gallbladder, which forms a fistula with the duodenum.
- Gallstone passes into the duodenum, and blocks it.
70
What are the investigations used for cholelithiasis?
- USS abdomen. If no stones shown, but blockage of the CBD (choledocholithiasis) still suspected, use MRCP (2nd line).
- LFTs. If uncomplicated (contained in gall bladder/cystic duct) LFTs normal. If obstructing the CBD, biliary pattern (Very high ALP, GTT, hyperbilirubinaemia).
71
What are the treatments for cholelithiasis?
- Analgesia as appropriate (paracetamol, diclofenac, buprenorphine etc.)
- For uncomplicated gall stones: Laparoscopic cholecystectomy.
- For choledocholithiasis: Initial ERCP to achieve biliary drainage THEN laparoscopic cholecystectomy.
72
What is liver cirrhosis?
- Liver cirrhosis is characterised by fibrosis and conversion of normal liver architecture into structurally abnormal nodules known as regenerative nodules.
73
What is the clinical presentation of liver cirrhosis?
- Abdominal distension.
- Jaundice.
- Hepatomegaly.
- Pruritus.
- Haematomesis (due to gastric varices).
- Melaena (due to GI bleeding caused by portal hypertension).
- Spider naevi.
- Hepatomegaly.
Many others too...
74
What are the risk factors of liver cirrhosis?
- Alcohol abuse (alcoholic liver cirrhosis).
- IV drug use/unprotected sex (Hep B/C).
- Obesity/diabetes (non-alcoholic fatty liver disease).
75
What is the pathophysiology of liver cirrhosis?
Liver cirrhosis activates the hepatic stellate cells. This causes:
- Collagen (I and III) deposition in the parenchyma.
- Stellate cells become contractile.
Both of these effects increase hepatic resistance, contributing to portal hypertension.
Portal hypertension can cause:
- Gastric varices.
- Ascites
Liver cirrhosis is reversible to a point. However, beyond that point it becomes irreversible - this is believed to be due to the deposition of elastin, which is resistant to remodelling.
76
What are the potential complications of liver cirrhosis?
- Portal hypertension.
- Gastric varices.
- Ascites.
- Hepatocellular carcinoma.
77
What are the investigations used for liver cirrhosis?
LFTs.
- Generally, there will be raised AST and ALT, with AST:ALT being greater than one.
- Hyperbilirubinaemia.
- Hypoalbuminaemia.
Prolonged INR/PT time.
Hyponatraemia.
GI endoscopy - Used to assess for gastric varices, and should be done every 1-3 years to screen for gastric varices for all with liver cirrhosis.
78
What is the treatment for liver cirrhosis?
- AVOID NSAIDS AND PARACETAMOL.
- Spironolactone (potassium-sparring diuretic) to treat ascites.
- Liver transplant (if permanently decompensated function).
- Propranolol (to treat gastric varices).
