Liver Flashcards
What are the functions of the liver?
Glucose + fat metabolism
Detoxification + excretion
Bilirubin
Ammonia
Drugs/hormones/pollutants
Protein synthesis
Albumin
Clotting factors – vitamin K
Defence against infection
What is the anatomy of the liver?
4 lobes - RIGHT, LEFT, CAUDATE + QUADRATE
Receives blood from the hepatic artery and portal vein.
Blood leaves through the hepatic vein.
Made up of repeating identical cells
2 sources of blood entering it: hepatic artery and the portal vein
Hepatic artery arises from the celiac artery so shares its BS with the upper bowel. It supplies all of the bile with oxygenated blood + some of the liver. The portal vein supplies all of the liver with blood that has drained from the bowel wall (therefore allows liver to process nutritional components from bowel) - partially deox as already has given some to bowel
What is bile?
Formed in the liver
Stored + concentrated in the gallbladder
Gallbladder is stimulated to contract + release stored bile by cholecystokinin (CCK)
This is released upon detection of food (fats) in stomach
Bile aids emulsification + digestion of fats
Contains
Cholesterol
Bile pigments - from broken down Hb
Phospholipids
What are the different LFTs?
Albumin = protein made by the liver, marker of function (useful for seeing severity of chronic liver disease. In acute disease, levels may be normal) IF LOW = OEDEMA
Bilirubin - raised = obstruction within biliary system (e.g. gallstone/pancreatic tumour pressing against bile ducts). But remember could also be raised by increased production in the first place.
Prothrombin time = how long does it take the blood to clot (to clot blood needs vitamin K which is made by the liver so without it time is prolonged). Often converted into INR
Alkaline phosphatase (ALP) - non-specific. Abnormal = liver or bone probs. Raised = consistent w biliary obstruction. Aminotransferases (Alanine aminotransferase (ALT) + aspartate aminotransferase (AST)) - markers of hepatocellular injury GGT - don’t worry about too much. Mainly used to confirm a raised ALP is due to biliary origin (is more fluctuating so not as reliable)
Albumin helps transport things in the blood that are not soluble in water, + it helps keep fluid in the correct place in the body. Low albumin= oedema , low protein so fluid leaks out
INR is the same as PT but expressed as a ratio
Raised alkaline phosphatase can also be caused by liver or bone malignancy, primary biliary cirrhosis, Paget’s disease of the bone and many other things.
In patients with cholestasis (e.g., due to gallstones), ALT and AST can increase slightly, with a higher rise in ALP (“an obstructive picture”).
If ALT and AST are high compared with the ALP level, this is more indicative of a problem inside the liver with hepatocellular injury (“a hepatitic picture”).
GGT enzyme produced by both damaged and proliferative bile duct cells.
also raised by binge drinking for example
What are bile pigments?
Bile pigments = substances formed from haem when old/damaged erythrocytes are broken down by macrophages (specifically KUPFFER CELLS) in the spleen/liver
What is jaundice?
Pre-hepatic = excess breakdown of Hb -\> increased unconjugated bilirubin (caused by EXCESS HAEMOLYSIS) Hepatic = failure of hepatocytes to take up, metabolise or excrete bilirubin Post-hepatic = obstruction of biliary system
In pre-hepatic conjugated bilirubin is still made + excreted normally so you have normal wee + poo
Causes:
Maleria
Sickle cell anaemia
Haemolytic disease of the newborn
Gilberts syndrome
Hepatic has raised conjugated + unconjugated
Hepatic causes:
Viral hepatitis
Drugs
Alcohol
Cirrhosis
Conjugated bilirubin can’t be got rid of so builds up. Absent urobilinogen
Pruritis as there are bile salts in circulation
Post-hepatic causes:
Gallstones
Pancreatitis (head of the pancreas blocks CBD)
V high AST/ALT suggests liver disease
What are the signs and symptoms of jaundice?
What is Charcot’s triad?
What are gallstones?
Biliary colic = Pain associated with the temporary obstruction of the cystic/common bile duct by a stone migrating from the gallbladder (no signs of cystic inflammation). When it falls back into the gallbladder symptoms resolve.
Cholelithiasis = formation of gallstones
Gallstone formation risk factors? 4Fs: Fat, Fertile, Forty, Female, Fhx
Colicky RUQ pain - worse after eating large/fatty meals (may radiate to epigastrum + back)
Can be assoc w N&V
Fat entering the digestive system causes cholecystokinin (CCK) secretion from the duodenum. CCK triggers contraction of the gallbladder, which leads to biliary colic. Patients with gallstones and biliary colic are advised to avoid fatty foods to prevent CCK release and gallbladder contraction.
Most gallstones are made of cholesterol. Can be asx
What is cholecystitis?
Gallstone is blocking the cystic duct -> bile builds up -> gallbladder becomes distended -> vascular supply decreases -> inflammation
Severe RUQ pain
Fever + fatigue
+ve Murphy’s sign = severe pain on deep inhalation when examiners hand is pressed into RUQ
What is cholangitis?
Prolonged common bile duct blockage -> bile does not flush out the tubes so bacteria can climb up the GI tract -> biliary tree infection
As bile cannot enter GI tract -> obstructive jaundice
Severe RUQ pain w/ fever (rigors) + yellowing skin
May present as septic (+ have some pancreatitis)
How do you investigate biliary disease?
TO SEE IF CHOLECYSTITIS/CHOLANGITIS:
FBC + CRP - signs of an inflammatory response is suggestive of cholecystitis
LFTs - raised ALP is assoc w biliary pathology (bilirubin + ALT are usually normal - but bilirubin is increased in cholangitis)
Amylase - to check for pancreatitis (will be raised)
DIAGNOSTIC TEST TO CONFIRM GALLSTONES = Transabdominal USS (stones, gallbladder wall thickness, duct dilation)
Magnetic Resonance Cholangio-Pancreatography (MRCP) - produces detailed image of biliary system - used if USS shows no stones in duct but there is dilatation or raised bilirubin
Endoscopic Retrograde Cholangio-Pancreatography (ERCP) - an endoscope is inserted down the oesophagus, past the stomach, to the duodenum + opening of common bile duct. Main indication is to clear stones. Can inject contrast to visualise system.
CT scans are less useful - for DDx
If cholangitis may want to do blood cultures
How are biliary diseases treated?
Analgesia
IV fluids if dehydrated
Antibiotics if inflammation/infection (i.e. fever)
Cholecystectomy (gallbladder removal - gallstones are likely to reoccur if not) - indicated in symptomatic px or where there are complications. Usually laparoscopic
ERCP + stenting to mechanically clear blockage from bile duct
Treat any sepsis asap in cholangitis!
What is acute liver injury?
Acute: results in damage to + loss of cells
Causes
Viral A, B, EBV
Drugs - paracetamol poisoning
Vascular – ischaemia
Obstruction – usually bile
Congestion – from heart failure
What is chronic liver injury?
Chronic: eventually leads to fibrosis (when severe = cirrhosis)
Cirrhosis – disorganisation + fibrous scarring
Varices – due to portal hypertension
Hepatoma
Causes
Alcohol
Viral B, C
Autoimmune
Metabolic (excess iron - haemochromatosis, copper – Wilson’s)
How does acute liver injury present?
Malaise
Nausea
Anorexia
Jaundice
How does chronic liver injury present?
Ascites (fluid accumulation in the peritoneal cavity)
Oedema
Haematemesis (ruptured varices) – vomiting blood
Malaise
Anorexia
Wasting
Easy bruising (since liver produces clotting factors)
Itching
Erythema nodosum
Spider naevi
Hepatomegaly
Abnormal LFTs
Jaundice (rarer)
Confusion (rarer)
Asterixis - flapping tremor
Get varices due to portal hypertension - biggest cause is cirrhosis. When the liver is injured myofibroblasts contract which resists BF
Also get splenomegaly as it -> splenic vasodilation
What is liver disease?
Alcoholic liver disease
Fatty liver -> alcoholic hepatitis -> cirrhosis
Non-alcoholic fatty liver disease
Healthy -> steatosis -> steatohepatitis -> fibrosis -> cirrhosis
Will have the sx + signs mentioned earlier. May have none.
RUQ pain
Nausea
Vomiting
Diarrhoea
Hepatomegaly
Ascites
Jaundice
Spider naevei
Most common cause of chronic liver dis in western world
Men in 40-50s
- Alcohol related fatty liver Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks.
- Alcoholic hepatitis Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.
- Cirrhosis This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
Non alcholic fatty liver disease (NAFLD) forms part of the “metabolic syndrome” group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes. It is estimated that up to 30% of adults have NAFLD. It is characterised by fat deposited in liver cells. These fat deposits can interfered with the functioning of the liver cells. NAFLD does not cause problems initially, however it can progress to hepatitis and cirrhosis.
How is liver disease investigated?
Bloods
FBC - elevated MCV, LFTs show elevated ALT + AST. ALP elevated later on in the disease, clotting will show elevated PT, U&Es (GGT very raised in alcoholic)
USS- may show the earlier fatty changes, can also show cirrhosis. A fibroscan is a specialised USS for the liver measuring fibrosis + steatosis
Liver biopsy - will confirm dx
Also in Fatty
Enhanced Liver Fibrosis (ELF) blood test + NAFLD fibrosis score
Endoscopy - to assess for + treat oesophageal varices
CT + MRI - fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.
How is liver disease treated?
Alcoholic
Stop drinking permanently - detoxification regime.
Vitamins + nutrient supplementation
Steroids for short term outcomes
Complications of cirrhosis - portal hypertension, varices, ascites, hepatic encephalopathy
Liver transplant (must be obtained from alcohol 3 months prior to referral)
Fatty
Weight loss + exercise
Control diabetes, BP + cholesterol
Avoid alcohol
Wernicke-Korsakoff encephalopathy (presents with ataxia, confusion + nystagmus)
Fatty liver is reversible cirrhosis is not
Alcoholic hepatitis: • Nutrition must be maintained with enteral feeding + if necessary vitamin supplementation • Steroids show short-term benefit • Infections should be treated and/or prevented; anti-fungal prophylaxis should be used • Stop drinking alcohol for life
Alcoholic cirrhosis: • Reduce salt intake • Stop drinking for life • Avoid aspirin + NSAIDs • Liver transplantation
Delirium Tremens
Delirium tremens is a medical emergency associated with alcohol withdrawal with a mortality of 35% if left untreated. Alcohol stimulates GABA receptors in the brain. GABA receptors have a “relaxing” effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors) having a further inhibitory effect on the electrical activity of the brain.
Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol. When alcohol is removed from the system, GABA under-functions and glutamate over-functions causing an extreme excitability of the brain with excess adrenergic activity. This presents as:
Acute confusion
Severe agitation
Delusions and hallucinations
Tremor
Tachycardia
Hypertension
Hyperthermia
Ataxia (difficulties with coordinated movements)
Arrhythmias
Managing Alcohol Withdrawal
The CIWA-Ar (Clinical Institute Withdrawal Assessment – Alcohol revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.
Chlordiazepoxide (“Librium”) is a benzodiazepine used to combat the effects of alcohol withdrawal. Diazepam is a less commonly used alternative. It is given orally as a reducing regime titrated to the required dose based on the local alcohol withdrawal protocol (e.g. 10 – 40 mg every 1 – 4 hours). This is continued for 5-7 days.
Intravenous high-dose B vitamins (pabrinex). This should be followed by regular lower dose oral thiamine.
Wernicke-Korsakoff Syndrome (WKS)
Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency.
Features of Wernicke’s encephalopathy
Confusion
Oculomotor disturbances (disturbances of eye movements)
Ataxia (difficulties with coordinated movements)
Features of Korsakoffs syndrome
Memory impairment (retrograde and anterograde)
Behavioural changes
Wernicke’s encephalopathy is a medical emergency and has a high mortality rate if untreated. Korsakoffs syndrome is often irreversible and results in patients requiring full time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.
What are the complications of liver disease?
Alcohol withdrawal
tremor, sweating, headache, craving and anxiety -> hallucinations -> seizures
-> Delirium tremens - treat with benzodiazepines (or diazepam)
Wernike-Korsakoff syndrome - alcohol excess leads to thiamine (vitamin B1) deficiency - give THIAMINE
Wernikes encephalopathy (medical emergency with high mortality rate) becomes Korsakoffs syndrome (irreversible, need full time care)
Ataxia, confusion, nystagmus, memory impairment
Mallory-weiss tear
Acute/chronic pancreatitis
What is liver cirrhosis?
The end stage of all progressive liver diseases. Irreversible once fully developed
Loss of normal hepatic architecture with bridging fibrosis + nodular regeneration.
This affects the BF through liver -> increased resistance -> portal HTN.
GD Dx is liver biopsy
Has a classification score called Child-Pugh - Ascites, encephalopathy, (high) bilirubin, (low) albumin + (long) prothrombin given 1-3 + added up to give a score
What are the signs of cirrhosis?
Signs of cirrhosis (taken from zero to finals - v v good resource):
Jaundice – caused by raised bilirubin
Hepatomegaly – however the liver can shrink as it becomes more cirrhotic
Splenomegaly – due to portal hypertension
Spider Naevi – these are telangiectasia with a central arteriole + small vessels radiating away
Palmar Erythema – caused by hyperdynamic cirulation
Gynaecomastia + testicular atrophy in males due to endocrine dysfunction
Bruising – due to abnormal clotting
Ascites
Caput Medusae – distended paraumbilical veins due to portal hypertension
Asterixis – “flapping tremor” in decompensated liver disease
Xanthelasma - yellow fat deposits under skin usually around eyelids
How is liver cirrhosis managed?
Treatment of underlying cause
USS every 6 months to screen for early hepatocellular carcinoma
Endoscopy every 3 yrs for px with known varices
High protein, low sodium diet
Liver transplant?
Manage complications
How are complications of cirrhosis managed?
Malnutrition
Varices due to portal HTN - do not cause sx unless they start bleeding
Propanolol
Elastic band ligation
TIPS (stent)
If bleeding resus + urgent banding, terlipressin
Ascites
Diruretics (spironolactone)
Low sodium diet
Ascitic tap
Hepatic encephalopathy
Bleeding Oesophageal Varices
Resuscitation
Vasopressin analogues (i.e. terlipressin) cause vasoconstriction and slow bleeding in varices
Correct any coagulopathy with vitamin K and fresh frozen plasma (which is full of clotting factors)
Giving prophylactic broad spectrum antibiotics has been shown to reduce mortality
Consider intubation and intensive care as they can bleed very quickly and become life threateningly unwell
Urgent endoscopy
Injection of sclerosant into the varices can be used to cause “inflammatory obliteration” of the vessel
Elastic band ligation of varices
What is hepatic encephalopathy?
As the liver fails, nitrogenous waste e.g. ammonia builds up in the circulation + passes to the brain which can result in permanent brain damage (ammonia is neurotoxic to the brain since it halts the Krebs cycle → IRREPARABLE CELL DAMAGE + neural cell DEATH)
As astrocytes try to clear ammonia (using a process involving the conversion of glutamate to glutamine), the excess glutamine causes an osmotic imbalance and a shift of fluid into these cells - hence cerebral oedema - resulting in damage
Confusion, coma, liver flap (asterixes - flapping tremor with wrist extended) + drowsiness
Treat cerebral edema with MANNITOL
LACTULOSE - to convert soluble ammonia to insoluble ammonium.
Four stages of hepatic encephalopathy
Altered mood and behaviour, disturbance of sleep pattern and dyspraxia
Drowsiness, confusion, slurring of speech and personality change
Incoherency, restlessness, asterixis
Coma
What is liver failure?
Hepatic failure occurs when the liver loses the ability to regenerate or repair, so that decompensation occurs
ACUTE HEPATIC FAILURE = acute liver injury w encephalopathy + deranged coagulation (INR > 1.5) in a patient with a previously normal liver
ACUTE-ON-CHRONIC HEPATIC FAILURE = liver failure as a result of decompensation of chronic liver disease
Paracetamol overdose is responsible for 50% of the cases in UK
Following ingestion of an overdose (12g in adults can be fatal) patients usually remain asymptomatic for the first 24 hrs and at most develop anorexia, nausea and vomiting with/without right upper quadrant pain
Liver damage is not usually detectable on liver biochemistry until at least 18 hours after ingestion
Liver damage reaches its peak with raised ALT + prothrombin time at 72-96 hrs after ingestion
Then will get jaundice + encephalopathy due to liver damage
With no treatment some patients will develop fulminant hepatic failure
Acute kidney injury due to acute tubular necrosis occurs in 25% of patients who have severe hepatic damage
Would see:
Metabolic acidosis
HYPOglycaemia (since overdose will inhibit glucose production (gluconeogenesis))
Prolonged prothrombin time
Raised creatinine
Treat
Gastric decontamination - ACTIVATED CHARCOAL
Give IV N-ACETYLCYSTEINE which acts by replenishing cellular glutathione stores • Rash is common side effect and treat with CHLORPHENAMINE • Do not stop unless anaphylactoid reaction with shock, vomiting + wheeze
What are the autoimmune liver diseases?
PRIMARY BILIARY CHOLANGITIS / CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
AUTOIMMUNE HEPATITIS
What is primary biliary cholangitis?
A chronic disorder with progressive destruction of small bile ducts (interlobar) -> obstruction of the outflow of bile = cholestasis -> back-pressure of this -> fibrosis, cirrhosis + liver failure
WOMEN 40-50YRS , may have other autoimmune diseases
Serum anti-mitochondrial antibodies (AMA) found in the majority.
Presentation
Jaundice - due to bilirubin
Hepatomegaly
Xanthelasma - due to raised cholesterol
Pruritus (usually earliest symptom) - caused by leakage of bile acids
Lethargy + fatigue
Joint pains
GI disturbance
Bile acids, bilirubin and cholesterol are usually excreted through the bile ducts into the intestines
Interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation → cholestasis (flow of bile from liver is reduced/blocked so can leak out into blood + other liver cells) which may lead to fibrosis, cirrhosis + portal hypertension.
Advanced stage can lead to cirrhosis due to autoimmune attack + infiltration of bile.
Serum anti-mitochondrial antibodies (AMA) found in majority.
Likely there is an environmental factor that acts of genetically predisposed hosts to trigger disease
Bile acids are normally responsible for helping the gut digest fats. Having a lack bile acids in the stool cause gastrointestinal disturbance, malabsorption of fats and greasy stools. Bilirubin normally causes the dark colour of stools, so a lack of bilirubin can cause pale stools.
How is primary biliary cholangitis investigated?
Increased ALP (first to be raised as has the most obstructive pathology) + cholesterol
AMA in 90% - most specific to PBC
Anti-nuclear antibodies (ANA) in 35%
ESR + IgM raised
Liver biopsy to dx + stage
How is primary biliary cholangitis managed?
Ursodeoxycholic acid reduces the intestinal absorption of cholesterol
Colestyramine - binds to bile acids to prevent absorption in the gut, can help with pruritus
Liver transplant in end stage liver disease
Immunosuppression (e.g. with steroids) is considered in some patients
Disease course and symptoms vary significantly. Some people live decades without symptoms. The most important end results of the disease are advanced liver cirrhosis and portal hypertension.
Some other issues / complications:
Symptomatic pruritus
Fatigue
Steatorrhoea (greasy stools due to lack of bile salts to digest fats)
Distal renal tubular acidosis
Hypothyroidism
Osteoporosis
Hepatocellular carcinoma
What is primary sclerosing cholangitis?
Condition where intra/extrahepatic ducts become strictured + fibrotic -> obstruction to the flow of bile out of the liver + into the intestines. Sclerosis refers to the stiffening + hardening of the bile ducts, + cholangitis is inflammation of the bile ducts. Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis + cirrhosis.
Male, 30-40, UC
Jaundice
Chronic right upper quadrant pain
Pruritus
Fatigue
Hepatomegaly
GS IX = MRCP - may show bile duct lesions or strictures
LFTs show an obstructive picture
ERCP to dilate strictures
This means alkaline phosphatase is the most deranged LFT + may be the only abnormality at first. There may be a rise in bilirubin as the strictures become more severe + prevent bilirubin from being excreted through the bile duct. Other LFTs (i.e. transaminases: ALT + AST) can also be deranged, particularly as the disease progresses to hepatitis.
Liver transplant can be curative but is associated with its own problems (around 80% survival at 5 years).
ERCP ((Endoscopic Retrograde Cholangio-Pancreatography) can be used to dilate + stent any strictures
Ursodeoxycholic acid - may slow disease progression
Colestyramine is a bile acid sequestrate in that it binds to bile acids to prevent absorption in the gut + can help with pruritus due to raised bile acids
Monitoring for complications (such as cholangiocarcinoma, cirrhosis + oesophageal varices)
No antibodies are highly sensitive or specific to PSC. They aren’t very helpful in diagnosis but they can indicate where there is an autoimmune element to the disease that may respond to immunosuppression.
Antineutrophil cytoplasmic antibody (p-ANCA) in up to 94%
Antinuclear antibodies (ANA) in up to 77%
Anticardiolipin antibodies (aCL) in up to 63%
What is the anatomy of the pancreas?
Exocrine cells: Acinar (cells that produce digestive enzymes to transport to duodenum) + their draining ductules
Endocrine: Islets of Langerhans
Alpha cells = glucAgon production
Beta cells = insulin production
D cells = somatosttin production (inhibits acinar enzyme secretion)
PP cells = pancreatic polypeptide (same)
Enterochrommaffin cells = serotonin production
Exocrine (no ducts, secreted directly to site of action, secrete enzyme, short term activity)
Functional unit of the exocrine pancreas comprises of an acinus + its draining ductule
A ductule from the acinus drains into interlobar (intercalated) ducts, which in turn drain into the main pancreatic ductal system
The main pancreatic duct itself joins the common bile duct to enter the duodenum as a short single duct at the ampulla of Vater
Acinar cells are responsible for the production of digestive enzymes e.g. amylase, lipase, colipase, phospholipase + the proteases (trypsinogen + chymotrypsinogen)
These enzymes are released by acinar cells + are then transported into the duodenum via pancreatic secretions
Stimulus for pancreatic secretion is gastric distension
Endocrine (ductless, released directly into the blood, secrete hormones, long term activity)
The endocrine component is scattered through the gland in the form of pancreatic islets of Langerhans
Alpha cell - glucagon production
Beta cells - insulin production
D cells - somatostatin (inhibits acinar enzyme secretion) production
PP cells - pancreatic polypeptide (inhibits acinar enzyme secretion)
Enterochrommaffin cells - serotonin production
What is acute pancreatitis?
Inflammation of the pancreas -> leakage of enzymes + autodigestion
Causes - think any acute injury
I - idiopathic
G - gallstones
E - ethanol
T - trauma
S - steroids
M - mumps
A - autoimmune
S - scorpion venom
H - hyperlipidaemia
E - ERCP
D - drugs - NSAIDs, ACEis
How does acute pancreatitis present?
Signs
Bruising around periumbilical region = CULLEN’S SIGN
Bruising on flanks = GREY TURNER’S SIGN
Tachycardia
Abdo guardian + tenderness
Distension
Fever
Jaundice
Dehydration
Hyperglycaemia from decreased insulin production
Symptoms
EPIGASTRIC PAIN RADIATING TO THE BACK - RELIEVED BY SITTING FORWARDS
N&V
Anorexia
Don’t confuse the pain from pericarditis - which usually presents in younger patients
Clinical dx
How is acute pancreatitis investigated?
INCREASED AMYLASE in serum + urine (but in serum it may be decreased 3/4 days after acute event, other things can also cause this e.g. upper GI perforation. Urinary may be diagnostic as levels remain elevated for a long time) - 3 fold upper limit of normal.
Increased lipase (this is more sensitive + specific)
Increased CRP - helps assess severity + prognosis
LFTs - Raised ALT + AST - but can normalise as the stone leaves. Elevated ALT >150 suggests gallstones
Need erect CXR to exclude gastroduodenal rupture
Abdo USS for gallstones
Contrast enhanced CT to find extent of necrosis
MRI - identify fluid + solid inflam masses
APACHE 2, Glasgow + Ranson scoring
How is acute pancreatitis managed?
Nil by mouth - to drop pancreatic stimulation. NG tube? - for dietary supplements - less pancreatic enzymes are released so need to support nutrition
Analgesics
Prophylactic abx (not if you think gallstones as can make worse)
Drainage of collections?
Assess severity!!
What are the complications of acute pancreatitis?
Complications (if left untreated/side effects of management)
Acute Respiratory Distress Syndrome – leading cause of death
Systemic inflammatory response syndrome (SIRS):
Pro-inflammatory state
Any two of: • Tachycardia greater than 90 bpm • Tachypnoea (fast breathing) greater than 20 breaths per min • Pyrexia with temperature greater than 38 degrees • High white cell count
Sepsis
Pancreatic pseudocyst
Hypovolaemic shock from ruptured vessels
DIC
What is chronic pancreatitis?
Obstruction of bicarbonate secretion in the pancreatic lumen causes early activation of trypsinogen + autodigestion which is replaced by fibrosis. (i.e. continual inflam process -> loss of pancreatic tissue -> fibrosis)
Causes:
Alcohol excess - commonest cause in dev world (60-70%)
CKD
Hereditary
Autoimmune
Presentation
Epigastric pain boring through back (worse after fatty food + alcohol, better on leaning forward)
50 year old male
N&V,
DM due to damaged B cells due to exocrine dysfunction
Malabsorption due to endocrine dysfunc - weight loss, steatorrhea, vitamin/protein def, diarrhoea
Steatorrhea (excess fat in faeces - pale, loose, foul smelling stools that float)
Key complications are:
Chronic epigastric pain
Loss of exocrine function, resulting in a lack of pancreatic enzymes (particularly lipase) secreted into the GI tract
Loss of endocrine function, resulting in a lack of insulin, leading to diabetes
Damage and strictures to the duct system, resulting in obstruction in the excretion of pancreatic juice and bile
Formation of pseudocysts or abscesses
How is chronic pancreatitis investigated?
Serum amylase + lipase (may be increased if there is enough cells to make them - in v advanced disease there is not sufficient residual acinar cells)
Abnormal faecal elastase
Abdo USS + contrast enhanced CT - detects pancreatic calcification + dilated pancreatic duct to CONFIRM DX
AXR - speckled calcification
How is chronic pancreatitis treated?
Alcohol cessation
Abdo pain control
Duct drainage
Pancreatic enzyme supplements
PPI to help digestion (-razole)
Insulin for DM
Surgery? Pancreatectomy
What is ascites?
Ascites is fluid in the peritoneal cavity.
Hypoalbuminaemia - reduced plasma oncotic pressure.
Portal hypertension - increased hydrostatic pressure. There is portal hypertension because there is increased intrahepatic resistance.
Renal water retention (peripheral arterial vasodilation mediated by NO etc.)
Ascites
Fluid in the peritoneal cavity
Cirrhosis commonest cause, 50% cirrhosis pts develop ascites in 10yrs.
4 basic mechanisms
Peritonitis - more leaky
Raised capillary hydrostatic pressure
Reduced colloid oncotic pressure
Peritoneal lymphatic draining
Transudate (protein <25g/L) - portal HTN (due to cirrhosis), Budd Chiari, low plasma protein, heart failure.
Exudate (protein >25g/L) - peritonitis, peritoneal malignancy
SHIFTING DULLNESS, gained weight, abdo distension.
Signs of liver disease.
Respiratory distress (pleural effusion).
Diagnostic aspiration (albumin, neutrophil count)
1st line - salt restriction.
Diuretics - furosemide/spironolactone.
SBP (8%) - an infection of ascitic fluid. Most common causes are E.coli then K.pneumoniae
Healthy men should have no fluid while in women up to 20ml is considered normal.
Peritoneal carcinomatosis
What is portal hypertension?
High blood pressure in the portal vein.
Causes:
prehepatic - portal vein thrombosis
Intrahepatic - schistosomiasis, cirrhosis.
Posthepatic - right sided heart failure
Asymptomatic, or Sx of complications:
Ascites
Bleeding varices
What are bleeding varices?
GI bleeds on a background of chronic liver disease
Most patients with cirrhosis develop varices, but only ⅓ bleed from them. Bleeding often massive.
Portal vein is formed by union of superior mesenteric (from the gut) and splenic vein (from the spleen) and transports blood into the liver through the porta hepatis
1st line/gold std Ix? Upper GI endoscopy
Portal vein is formed by union of superior mesenteric (from the gut) and splenic vein (from the spleen) and transports blood into the liver through the porta hepatis
Melaena
Haematemesis (coffee ground vomit)
What do you do for actively bleeding varices?
Urgent gastroscopy/endoscopy
Fluid resuscitation, remember can be massive
Terlipressin (ADH analogue) or Octreotide
Balloon tamponade
Gold std - endoscopic therapy: bang ligation or
sclerotherapy.
60-80% of recurrence within 2yrs, so we give
secondary prophylaxis:
Propranolol / Isosorbide
Repeat variceal banding
TIPSS
ADH analogue for hypovolaemia, also constricts splanchnic arteries to reduce bleeding)May give somatostatin/Octreotide which lowers portal pressure by same mechanisms.
How do you remember viral hepatitis?
A is Acquired by mouth from Anus, is Always cleared Acutely and only ever Appears once
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 a Cost. Caused by Crack (IVDU).
E is Even in England and can be Eaten (found in pigs), if not alway beaten
What is hepatitis A?
Virus type
RNA
Transmission
Faecal-oral: contaminated food, fly vectors
Epidemiology
Rarer, high prevalence in Africa, Asia, South America, Middle east.
Pathophysiology
Acute infection usually cleared by host immune system.
Presentation
Non-specific symptoms - nausea, anorexia, malaise,
After 1-2weeks liver symptoms - jaundiced, hepatomegaly, skin rash.
Investigations
LFTs - raised ALT, raised bilirubin, serology
Treatment
Vaccine is available
Treatment often not required, generally supportive.
Complications
Rare, acute liver failure.
What is hepatitis B?
Virus type
DNA virus (only DNA one).
Transmission
Blood products (IVDU), sexually (particularly MSM).
Vertical transmission is most common transmission worldwide.
Epidemiology
Present worldwide, prevalent in Africa, Middle and Far East.
Pathophysiology
Acute infection infects hepatocyte. Cellular response usually clears it.
Chronic HBV (5%) if HBsAg >6 months. Depends on age/ immunocompetence. Inflammation can last 10 yrs -> cirrhosis.
Presentation
Similar acute infection.
If chronic, then signs of cirrhosis - jaundice, pruritus etc.
Investigations
LFTs, serology. If Ag after 6 months then can confirm chronic HBV.
Treatment
Vaccine available - given to those at risk (probs got it in 1st yr).
Antiviral treatment - Tenofovir, pegylated interferon alpha 2a
Complications
If chronic, increased risk of liver cirrhosis, hepatocellular carcinoma
What is hepatits D?
Virus type
RNA
Transmission
Blood borne - sexually, IVDU
Pathophysiology
Unable to replicate on its own, requires concurrent HBV infection.
It makes Hep B infection more likely to progress to cirrhosis/HCC
Presentation
Clinically indistinguishable from acute HBV infection
Treatment
Same as HBV
Complications
Cirrhosis and HCC
What is hepatitis C?
Virus type
RNA
Transmission
Blood/blood products - IVDU more than sexually.
Epidemiology
More common in UK. Again common in Africa.
Pathophysiology
Acute infection often asymptomatic, allowing it to become chronic.
Chronic HCV infection causes a slowly progressive fibrosis over years.
Presentation
Acute = asymptomatic. Later on signs of chronic liver disease.
Investigations
LFTs, serology. If Ag after 6 months then can confirm chronic HCV.
Treatment
Treatment is revolutionising from interferon based regimens to directly acting antiviral agents (Ribavirin) - expensive.
Complications
Chronic liver disease, hepatocellular carcinoma
What is hepatitis E?
Virus type
RNA virus
Transmission
Faeco-oral transmission (undercooked meat)
Epidemiology
Common in UK
Presentation
95% of cases are asymptomatic, as usually self-limiting
Investigations
Serology
Treatment
Often not required, but supportive.
Complications
Rare. Can progressive to cirrhosis in immunocompromised.
What is haemachromatosis?
Definition
Multi-system disorder of dysregulated dietary iron absorption and increased Iron release from macrophages
Aetiology
Autosomal recessive, can get secondary Iron overload caused by multiple transfusions.
Epidemiology
Rare.
Pathophysiology
Iron accumulates in liver, joints, pancreas, heart, skin and gonads.
Presentation
SLATE GREY SKIN
Hypogonadism (ED), or other Sx of complications (e.g. arrhythmias)
Investigations
Bloods - Iron, LFTs.
Diagnostic is liver biopsy.
Treatment
Venesection 1st line. Iron chelation 2nd line. Definitive = liver transplant
Complications
Cirrhosis, HCC, diabetes, heart disease.
What is Wilson’s disease?
Definition
Too much copper, that builds up in the liver and CNS
Aetiology
Autosomal recessive, defective enzyme involved in biliary excretion of excess copper.
Epidemiology
Rare.
Pathophysiology
Cu2+ accumulates in the liver (liver symptoms), basal ganglia (Parkinson’s symptoms) and cornea (kayser-Fleischer rings).
Presentation
Liver problems with psychiatric/neurological presentation - Parkinsonian, depression, neurotic behavioural patterns.
Kayser-Fleischer ring
Investigations
1st line - 24hr urine copper and blood caeruloplasmin. Definitive is liver biopsy.
Treatment
Pencillamine (copper chelation). Liver transplant
Complications
Liver failure, neurological problems.
What is liver cancer?
Hepatocellular carcinoma - 80% of cases
Presentation → chronic liver failure +- abdo mass
Risk Factors → HCV and HBV(80%), EtOH, Aflatoxin
Investigations → LFTs, Clotting studies, CT, MRI, Ultrasound guided Biopsy
Treatment - depends on staging
Partial Hepatectomy or Transplant - curative intention
Chemotherapy to downstage and possibly resect or as palliative chemo to prolong life
Prognosis → 3-6 months if unresectable - 90%
What is pancreatic cancer?
Pancreatic adenocarcinoma accounts for 90%
Who? Men > women, above 65, smokers, obese, chronic pancreatitis, family history
Clinical Presentation:
Unrelenting epigastric pain worse at night - 46%
Obstructive Jaundice +- pain
Weight loss and anorexia
Palpable gallbladder (courvoisier’s sign)
Recent diagnosis of DM
Trousseau’s sign - Migratory thrombophlebitis
Investigations
Bloods - Carbohydrate antigen 19-9 + LFTs
CT +- Endoscopic USG
Biopsy with histological confirmation
Management
Surgery - Whipple’s procedure
Chemo - Neoadjuvant, adjuvant or palliative
Prognosis
6% overall 5 year survival
