Liver & Co. Flashcards
what are the fat soluble vitamins?
A, D, E, K
name 3 functions of phase I reactions in liver detoxification?
- inactivate drugs
- further activate drugs
- activate drug from pro-drug
- make a drug into a reactive intermediate
What is the purpose of phase 1 reactions?
addition / exposure of a reactive site that can be used for conjugation reactions in phase 2 (functionalisation)
what are phase 1 reactions catalysed by?
cytochrome P450 enzymes
what is the purpose of phase II reactions?
to increase the hydrophilicity of the drug for renal excretion
what is the general mechanism for phase II reactions?
They are conjugation reactions.
Attachment of substituent groups, reaction catalysed by transferases.
what type of reactions take place during phase I reactions?
oxidation, reduction and hydrolysis
what is the function of albumin?
binding and transport of large hydrophobic compounds e.g bilirubin
what clotting factors does the liver not produce?
calcium and von Willebrand factor
what clotting factors need Vitamin K for their synthesis?
10, 9, 7, 2 (1972)
what is the role of complement factors?
plasma protein which opsonizes
what is a portal tract
contains branches of portal veins, arteries and bile duct
what are sinusoids?
highly specialised blood vessels that permits the exchange of material within blood
what are the stem cells in the liver known as
hepatic stellate cells
what are Kupffer cells
resident macrophage in the liver
what is the space of Disse
space between the vascular endothelial cells of the sinusoid and the hepatocyte (perisinusoidal space)
what is the path from synthesis to storage of bile?
- hepatocytes synthesise bile
- bile drains into the canaliculi which lie inbetween individual hepatocytes
- then into bile ductules
- then to bile ducts
- if bile does not pass straight into the duodenum then it is stored in the gallbladder.
what attaches the liver to the anterior abdominal wall
falciform ligament
what is the bare area of the liver
large area on diaphragmatic surface of liver that is directly attached to the diaphragm
what are the lobes of the liver
right lobe
left lobe
caudate lobe
quadrate lobe
what is the anatomy of the biliary tree
- Right and left hepatic ducts join to form the common hepatic duct
- The cystic duct is comes from the gallbladder and joins the common hepatic duct to form the common bile duct
- Pancreatic duct joins onto the common bile duct to form ampulla of Vater
- Bile duct enters the descending part of the duodenum at the major duodenal papilla (where the ampulla of Vater is located )
what are the contents of bile?
- bicarbonate ions
- cholesterol
- lecithin
- bile pigments
- bile salts
what is bile used for?
the emulsification and absorption of fats in the the duodenum
what is the predominant bile pigment
bilirubin - a yellow substance resulting from heme breakdown
Outline bilirubin metabolism
- RBC are produced in bone marrow by erythropoesis
- when RBC become damaged/old macrophages in the spleen/bone marrow engulf and degrade them
- Hb molecule released
- Hb breaks down into heme and globin
- Heme is metabolised into Fe2+ and BILIVERDIN (green pigment)
- Biliverdin is rapidly reduced into UNCONJUGATED BILIRUBIN (UCB)
- UCB is yellow, toxic and lipid soluble
- UCB binds to albumin and is transported to the liver
- UCB enters the liver and undergoes a conjugation reaction with glucoronic acid to become CONJUGATED BILIRUBIN which is water soluble
- conjugated bilirubin can be excreted by the liver in bile through the common bile duct
- Conjugated bilirubin travels through the SI to the LI
- Colonic bacteria in the LI converts conjugated bilirubin to UROBILINOGEN which is lipid soluble
- 10-15% of urobilinogen is reabsorbed by the blood and taken back to the liver. 5% transported to kidneys and converted to yellow UROBILIN which is excreted in urine
- 85-90% of urobilinogen is oxidised by other intestinal bacteria to STERCOBILIN which is a brown coloured pigment that colours the feces
what is the general aetiology behind jaundice?
excess bilirubin in the plasma
what are the three different classifications of jaundice?
- Prehepatic
- Hepatic
- Post hepatic
what is the pathology of pre-hepatic jaundice
produced by conditions where there is an excessive breakdown of erythrocytes (increased rate of haemolysis) which overwhelms the livers ability to conjugate
there is excess unconjugated bilirubin in the plasma
3 conditions that can cause pre-hepatic jaundice?
- malaria
- sickle cell
- thalassaemia
- Gilbert’s syndrome
what is the pathology of hepatic jaundice?
biochemical reactions converting fat soluble into water soluble bilirubin may be affected by inflammatory change within the liver or necrosis
There is a build up of conjugated and unconjugated bilirubin in the blood (cannot conjugate as not enough cells, plus inflammation/cirrhosis may compress the intra-hepatic portions of the biliary tree causing some obstruction in excretion)
Name 3 causes of hepatic jaundice?
hepatitis
alcoholic liver disease
drug misuse (paracetamol overdoes)
primary biliary cirrhosis
what is the pathology behind posthepatic jaundice?
any obstruction of the biliary tree can produce jaundice
increase in conjugated bilirubin
3 causes of post hepatic jaundice?
gallstones
pancreatic cancer in the head of the pancreas (an obstructing tumour)
gallbladder / bile duct cancer
what are the features of pre-hepatic jaundice on the bowel
?
normal stools and urine
what are the features of hepatic jaundice?
- raised bilirubin in urine
- dark coloured urine
- normal stools
what are the features of post hepatic jaundice?
dark urine
pale stools
Conjugated bilirubin is water soluble, so is excreted in urine and makes it dark. Less conjugated bilirubin enters the gut and faeces become pale.
What are the general clinical features of jaundice?
Yellow skin and sclerae
Itching
Investigations in jaundice patients
Underlying cause can be elicited from the history.
Liver Function Tests
Bilirubin
Albumin (marker of liver synthesis function)
AST and ALT (markers of hepatocellular inkjury)
Alkaline Phosphatase (raised in biliary obstruction)
Coagulation studies (prothrombin time can be used as a marker of liver synthesis function)
FBC (anaemia, raised MCV and thrombocytopenia seen in liver disease)
Ultrasound Dilated bile ducts? Gallstones? Hepatic metastases? Pancreatic mass?
MR Cholangiopancreatography used to visualise biliary tree in obstructive jaundice if US abdomen was inconclusive or limited.
Treatment of jaundice
Definitive treatment depends on the underlying cause
Symptomatic treatment is often needed for itching e.g antihistamines if not post-hepatic
Broad spectrum antibiotics if obstruction
Hydration
what are the functions of the liver?
Protein synthesis
Detoxification and excretion
Glucose and fat metabolism
Defence against infection (reticuloendothelial system)
how is liver injury classified and what does each entail?
- Acute (direct hit to the liver resulting in acute hepatocyte injury and death)
- Chronic (if the liver injury persists for more than 6 months. Can cause scarring and fibrosis which has the potential to result in liver failure)
Name three causes of acute liver injury?
- Viral hepatitis (A, B)
- EBV
- Glandular fever
- Drugs
- Alcohol
Name three causes of chronic liver injury?
- Autoimmune hepatitis
- Primary biliary cirrhosis
- Haemochromatosis
- Alcohol
- Viral hepatitis
Presentation of acute liver injury?
- malaise
- nausea
- anorexia
- jaundice
- sometimes liver pain
If the liver is inflamed where does pain radiate?
Right shoulder as inflammation of the liver may cause irritation to the diaphragm (phrenic nerve)
Presentation of chronic liver injury?
- peripheral oedema which can lead to ascites
- upper GI bleed
- Malaise, anorexia
- Wasting
- Bruising
- Itching
- Hepatomegaly
- Extensive spider naevus
what three liver function tests give index about liver function? What do they each mean?
Serum bilirubin
- usually all unconjugated
- in liver disease increased serum bilirubin
Serum albumin
- marker of synthetic function of the liver and useful for estimating the severity of chronic liver disease
Prothrombin Time
- marker of synthetic function of the liver
What are the liver function tests that give NO index of liver function?
serum liver enzymes
- Alkaline phosphatase
- Gamma-GT
- Alanine aminotransferase (ALT)
- Aspartate aminotransferases (AST)
what can an elevated Alk Phos show?
- May originate from the liver, bone or placenta
- Usually raised due to a disorder of the bone or liver
- Raised levels can also occur with hepatic infiltrations e.g mets
where is gamma-GT present in the body?
liver, pancres, renal tubules and intestine
what 2 other factors may be present which make it more likely that an elevated alkaline phosphate is caused by the liver?
- Raised Gamma-GT
- Other raised liver function tests (serum albumin, bilirubin, prothrombin time)
when are transaminase enzymes seen in the blood?
usually these enzymes are contained in hepatocytes and leak into the blood with hepatocellular injury
when does liver failure occur?
when the liver loses the ability to regenerate or repair so that decompensation occurs.
Can be acute or chronic
causes of liver failure?
Infections Viral hepatitis (B and C) Cytomegalovirus Epstein Barr Virus Herpes Simplex Virus
Drugs Paracetamol Alcohol Anti-depressant (amitriptyline) NSAIDs Cocaine Antibiotics
Toxins
Vascular
Budd Chiari Syndrome
What is Budd Chiari Syndrome
Hepatic vein obstruction by thrombosis or tumour causes conjestive ischaemia and hepatocyte damage
Signs of liver failure
Hepatic encephalopathy Jaundice Abnormal bleeding: variceal bleeding Small liver Fever Vomiting Cerebral oedema
Why does liver failure cause encephalopathy?
Why can it also cause cerebral oedema?
ammonia builds up in the circulation and passes to brain. Ammonia = neurotoxic so can cause permanent brain damage. Stops the Kreb’s cycle causing neural cell death.
Astrocytes clear the ammonia to produce glutamine. Excess glutamine causes osmotic imbalance and cerebral oedema
What are the stages of hepatic encephalopathy?
I - sleep disturbance
II - drowsiness, confusion, behaviour change
III - restless, liver flap
IV - coma
Investigations in Liver Failure?
Bedside test for encephalopathy:
- Serial 7s
- Spell WORLD backwards
- Count as many animals in 1 min
- Draw a 5 pointed star
- Number connection test
Liver Function Tests
- Hyperbilirubinemia
- High serum ALT, AST
- Low coagulation factors (raised prothrombin time)
- Hypoalbuminemia
Bloods
High ammonia levels
Imaging
US - liver size
CXR
Doppler ultrasound to see hepatic vein patency
Microbiology (to rule out infection)
Blood culture
Urine culture
Ascitic tap
Management of liver failure?
Beware of sepsis, hypoglycaemia, GI bleeds.
Treat the underlying cause if known
Administer IV glucose if needed
Mineral supplements (calcium, potassium, phosphate)
Thiamine and folate supplements
Manage coagulopathy with IV Vitamin K, platelets, blood or fresh frozen plasma
Consider omeprazole as prophylaxis against ulceration and GI bleeds
Liaise with transplant centre
what is acute-on-chronic liver failure
acute decompensation of the liver caused by a failure of the liver to compensate for the functional overload resulting from the chronic liver disease
what is fulminant hepatic failure?
clinical syndrome defined as the rapid development of acute liver injury with severe impairment of the synthetic function and hepatic encephalopathy in a patient without obvious, previous liver disease
aetiology (3 causes) of fulminant hepatic failure?
drug induced liver failure (commonly paracetamol)
Viral hepatitis (B)
Vascular (Budd-Chiari Syndrome)
Wilson’s disease (rare)
name 2 mechanisms by which drugs can cause liver damage?
- disruption of intracellular Ca2+ homeostasis
- Disruption of bile canalicular transport mechanisms
- Induction of apoptosis
- Inhibition of mitochondrial function, prevents fatty acid metabolism and accumulation of ROS
if they are going to, what is the time frame that drugs usually cause drug induced liver damage?
1-12 weeks
name two antibiotics known to cause jaundice?
Augmentin
Flucloxacillin
Erythromycin
pathophysiology of paracetamol overdose
- Too much paracetamol
- Increase in the cytochrome P450 metabolism pathway
- Increase in NAPQI
- Insufficient amount of glutathione stores
- Increase in unconjugated NAPQI which binds to hepatic macromolecules causing hepatocyte injury
Symptoms of paracetamol overdose?
Asymptomatic for the first 24 hours
Anorexia Nausea Vomiting RUQ pain Jaundice Encephalopathy
Treatment for paracetamol overdose?
Activated charcoal for gastric decontamination
N acetyl Cysteine (NAC) to replenish glutathione stores
Supportive treatment
Liver transplant if severe
Pathophysiology of biliary colic
Temporary, severe abdominal pain caused by gallstones becoming lodged in the bile ducts.
After a meal, gallbladder contracts ejecting the gallstone into the cystic duct where it becomes stuck. Gallbladder continues to contract against the lodged gallstone. Can cause sudden, dull pain in the RUQ.
After 6 hours the gallstone usually dislodges, rolls back into the gallbladder and pain subsides
Aetiology of biliary colic (name 3)
Gallstones Narrow Bile Duct Pancreatitis Duodenitis Oesophageal spasms
name 4 risk factors that increase likelihood of developing gallstones
Fat
Female
Fertile
Forty
Symptoms of biliary colic
Sudden DULL pain in the RUQ which can radiate to the right shoulder
- Usually comes on after a meal or at night when lying flat
- Severity increases for 15 minutes then plateaus for 6 hours
Nausea
Vomiting
Sweating
Anorexia (because pain is so bad after eating)
Investigations and diagnosis of biliary colic
Diagnosis is based on recurring symptoms
Ultrasound of RUQ can show an obstruction
Treatment of biliary colic
Analgesic to manage pain and symptoms e.g opioid such as morphine
Cholecystectomy
what is a complication of biliary colic?
if the gallstone does not dislodge and stays in the cystic duct for prolonged periods of time it can lead to acute cholecystitis
what is cholecystitis defined as?
inflammation of the gallbladder
Pathology of acute cholecystitis
Person has gallstones in gallbladder
Small intestine secretes CCK → bloodstream → constricts the gallbladder to secrete bile
Gallbladder constricts
Gallstone becomes stuck in cystic duct, blocking the flow of bile
Gall bladder stretches and irritates the nerves of the gallbladder and cystic duct
Bile is in a state of stasis as it cannot exit the gallbladder.
Bile irritates the mucosa in the walls of the gallbladder to start secreting mucus and inflammatory enzymes which results in inflammation, distension and increasing pressure.
Name three possible progressions from acute cholecystitis
- Stone falls out of cystic duct and symptoms subside
- Pressure in gallbladder continues to increase, constricting the blood vessels which supply it. Leads to ischaemia and gangrenous cell death. Gallbladder has potential to rupture causing biliary peritonitis or sepsis.
- Gallstone can get stuck further down the common bile duct. Block the flow of bile out of the liver. Increase in conjugated bilirubin in blood which can cause jaundice.
- Cholangitis (bacterial growth)
aetiology of acute cholecystitis
gallstones stuck in cystic duct
Symptoms of acute cholecystitis
- Midepigastric pain
- Nausea
- Vomiting
- Anorexia
- Jaundice
- Low grade fever
Signs of acute cholecystitis? What is involved in each of these tests?
- Blumberg’s sign / rebound tenderness (RUQ pain when pressure is RELEASED from the abdomen)
- Positive Murphy’s sign (examiner places hand below the right costal margin after patient has exhaled- if patient suddenly stops breathing in due to the pain then this confirms diagnosis)
Investigations used in acute cholecystitis
What does each test show
Murphy’s sign
Imaging
- US : detect stones, gallbladder wall thickening, sludge (build up of substances in the gallbladder), distension of gallbladder or bile duct
- Cholescintigraphy : radiolabelled marker used to visualise the biliary system
- Endoscopic retrograde cholangiopancreatography
- MRCP to visualise biliary tree
LFTS
- Elevated ALP
- Elevated leukocyte count due to inflammation and CRP
- Raised serum bilirubin
Treatment options for acute cholecystitis
In 90% of cases the gallstone dislodges
Supportive :
IV fluids
Pain management (opiates)
IV antibiotics
Laparoscopic cholecystectomy
Stone dissolution : for (near) pure cholesterol stones can give oral ursodeoxycholic acid
Shock wave lithotripsy : shock wave directed onto gallbladder stones to turn them into fragments so they can be passed
Pathology of chronic cholecystitis
Constant state of gallbladder inflammation caused by recurrent obstruction of the cystic duct by a gallstone.
Chronic inflammation changes the gallbladder wall structure - damage to the epithelial cells. Can also lead to deep grooves and pockets of mucosa
What complication can arise due to chronic cholecystitis
Can lead to fibrosis and calcification of the epithelial tissue → porcelain gallbladder.
Gallbladder becomes hard and brittle with a bluish discolouration
Why is there calcification of the gallbladder in chronic cholecystitis
Calcification is caused by bile stasis, may cause calcium carbonate bile salts to precipitate out and deposit into walls.
Aetiology of chronic cholecystitis
Constant state of inflammation caused by recurrent obstruction of the cystic duct by a gallstone
Symptoms of chronic cholecystitis
- Midepigastric pain (DULL pain radiating to the right shoulder)
- Nausea
- Vomiting
- Anorexia
- Jaundice
- Low grade fever
- Distension
- Flatulence
Signs of chronic cholecystitis
Blumberg’s sign
Positive Murphy’s sign
Investigations in chronic cholecystitis
Murphy’s sign
Imaging
US - sonographic murphy’s sign, detect stones, gallbladder wall thickening, sludge, distension
Cholescintigraphy : radiolabelled marker used to visualise the biliary system, if there is blocked duct the gallbladder cannot be seen.
Treatment of chronic cholecystitis
Laparoscopic cholecystectomy
Aetiology of gallstones (name three causes)
Obesity
Rapid weight loss: imbalance in bile composition leads to increased risk of calcium-bilirubin precipitation
Diabetes mellitus
Oral contraceptive pill : increase in oestrogen leads to an increase in bile and bile hypomotility
Liver cirrhosis
Risk factors (name 5) for developing gallstones
Female Fat Forty Fertile Smoking OCP Rapid weight loss
How are cholesterol stones made and what features do they have
- Cholesterol crystallisation in bile due to either a relative deficiency in bile salts and phospholipids or excess cholesterol (diabetes or hypercholesteraemia)
- not visible on X-ray
- Large, solitary
- Mainly cholesterol
What are two features of pigment gallstones ?
- small stones
- friable
- can be seen on X-ray
How are black pigment stones formed
excessive haemolysis leads to an increase in unconjugated bilirubin. Unconjugated bilirubin binds to calcium and precipitates out to form black pigment stones.
How are brown pigment stones formed
Caused by a gallbladder/biliary infection. Infectious organisms bring hydrolytic enzymes which hydrolyze conjugated bilirubin and phospholipids. Combines with calcium ions and precipitate out to form stones.
name one common infections that can cause brown pigment stone formation
E. coli
Ascaris lumbricoides
complications that can be caused by gallstones
Cholecystitis
Ascending cholangitis
Blockage of common, pancreatic bile ducts
Gallbladder cancer
Symptoms of gallstones
May be asymptomatic
Sudden, intense abdominal epigastric pain that radiates to the right shoulder
Nausea, vomiting, jaundice, abdominal tenderness, distension, fever, chills, flatulence
What are the treatment options for gallstones?
Only if symptomatic!
Medial : bile salts to dissolve cholesterol stones
Surgery : cholecystectomy
Pain management
Lithotripsy
Investigations in suspected gallstones
Ultrasound
LFTs
Elevated bilirubin
Raised GGT, ALP, ALT and AST
what is ascending cholangitis
inflammation of the bile ducts from a bacterial infection
Pathology of ascending cholangitis
Flow of bile is blocked due to gallstones or a stricture
Bacteria can make its way from the duodenum up the bile duct and colonise the biliary system. Bacteria can continue to ascend and infect the stagnant bile as well as the surrounding tissue
Complications that can arise from ascending cholangitis?
Why?
- sepsis –> multi organ failure
Bile duct is under high pressure from the obstruction. Can cause the spaces between the cells lining the ducts to widen, allowing the bacteria and bile to enter the bloodstream
Aetiology of ascending cholangitis
E. coli
Klebsiella
Enterococcus
Symptoms of ascending cholangitis
Biliary colic
Charcot’s triad
Fever
RUQ pain
Jaundice (dark urine and pale stools)
Reynold’s pentad
Charcot’s triad
Hypotension (caused by septic shock)
Confusion (caused by decreased blood flow to the brain)
Investigations in ascending cholangitis
Blood tests :
Increased WBC (FBC)
Increased CRP
LFTs
Elevated
Imaging
- Ultrasound
- Endoscopic retrograde cholangiopancreatography
- Abdomen CT can exclude carcinoma of the pancreas and makes it easier to spot pigmented stones causing an obstruction
What is an endoscopic retrograde cholangio-pancreatography?
Endoscope placed through mouth until get to the ampulla of Vater
Insert a cannula into the biliary tree and inject contrast material
X-rays taken to study the biliary tree
What is the management plan and the treatment options in ascending cholangitis?
Rehydration
IV antibiotics : piperacillin-tazobactam
Remove obstruction : ERCP, shockwave lithotripsy
Widen ducts with a stent if a stricture is the cause
Cholecystectomy is recommended to avoid future gallstone complications
What are the functions of the pancreas?
Endocrine : secrete glucagon and insulin
Exocrine: make digestive enzymes that are secreted into the duodenum and break down macromolecules. Made and stored as zymogens and activated by proteases.
what is acute pancreatitis
sudden inflammation and haemorrhaging of the pancreas
Name two risk factors for developing acute pancreatitis
Female
Smoking
Pathology of acute pancreatitis
Caused by destructive effect of premature activation of pancreatic enzymes which causes pancreatic inflammation by the enzyme mediated autodigestion.
aetiology of acute pancreatitis - name 5 causes
I GET SMASHED
Idiopathic GALLSTONES ETHANOL ABUSE Trauma Steroids Mumps Autoimmune Scorpion sting Hypertriglyceridemia and hypercalcaemia ERCP Drugs
how does alcohol abuse lead to acute pancreatitis?
- alcohol increases zymogen secretion from acinar cells and decreases fluid and bicarbonate production from the ductal epithelial cells
- pancreatic juices become very thick –> potential blockage of pancreatic duct
- distension of pancreatic duct
- due to distension zymogen granules fuse with lysosomes bringing trypsinogen into contact with lysosomal digestive enzymes leading to autodigestion of the pancreas
how do gallstones lead to acute pancreatitis?
- Gallstone stuck in the sphincter of Oddi
- Blocks the release of pancreatic juices
- Intracellular Ca2+ increases and causes the early activation of trypsinogen
What complications can arise from acute pancreatitis
Pancreatic pseudocysts (form due to fibrous tissue surrounding the liquefactive necrotic tissue)
Haemorrhage
DIC
ARDS
Symptoms of acute pancreatitis
Nausea Vomiting Umbilical and flank bruising Upper abdominal pain, radiation to the back which may be relieved by sitting forwards Anorexia Jaundice Fever
Signs of acute pancreatitis
Hypocalcemia
Cullen’s sign (periumbilical region bruising caused as necrosis induced haemorrhaging spreads to soft tissue )
Grey Turner’s sign ; bruising around the flank
Abdominal pain, palpable tender mass
Dehydration
Hypotension
Tachycardia
Investigations for acute pancreatitis
Pain in epigastric region that radiates to back
Blood tests
Increase in serum amylase
Raised serum lipase
CT Scan of abdomen
Visualisation of inflammation, necrosis, pseudocysts
Ultrasound : looking for gallstones which may be the cause
Pancreatic scoring systems e.g APACHE II to assess severity
Treatment / management for acute pancreatitis?
Assess severity!
IV morphine
Hydration
Electrolytes
Nasogastric tube for dietary supplements to rest the bowels.
Urinary catheter
Treat any complications
Oxygen therapy
Antibiotics
If pancreatic necrosis suspected consider a laparotomy and debridement
what is chronic pancreatitis?
chronic, persistent inflammation of the pancreas often due to repeated episodes of acute pancreatitis
pathophysiology of chronic pancreatitis
Repeated episodes of acute pancreatitis lead to healthy pancreatic tissue being replaced by misshapen ducts, fibrinolytic tissue lay down by stellate cells and calcium deposits (these are caused by alcohol acute pancreatitis)
Aetiology of chronic pancreatits? (Name 5 causes) `
LONG TERM ALCOHOL EXCESS Recurrent acute pancreatitis Autoimmune Smoking Cystic Fibrosis
Clinical presentation of chronic pancreatitis
Pain in epigastric region - Can radiate to back - Often lasts for hours - May be linked to meals - May be relieved by sitting forwards or hot water bottles on the epigastric region/back Bloating Steatorrhoea Weight loss Nausea Vomiting Symptoms relapse and worsen
Investigations in chronic pancreatitis
Pancreatic biopsy
- Dilatation of pancreatic ducts
- Acinar cell atrophy
- Fibrosis
- Chronic inflammatory infiltrate
- Calcifications
Imaging - Abdominal XRays - Abdominal CT - Abdominal US - MRCP May show calcifications with confirm diagnosis
Treatment / management for chronic pancreatitis
Analgesics for pain relief (coeliac plexus block)
No alcohol
Low fat diet
Give fat soluble vitamins and lipase
Insulin needs may be high or variable - beware of hypoglycaemia
Surgery is indicated in those with unremitting pain, narcotic abuse and weight loss e.g pancreatectomy or pancreaticojejunostomy
What is the pathology behind alcoholic liver disease?
Alcohol excess leads to increased metabolism via the alcohol dehydrogenase pathway to produce more acetaldehyde.
Causes increased fat production and abnormal lipid retention in the hepatocytes (steatosis) which leads to fatty liver.
Also form reactive oxygen species which lead to tissue injury and fibrosis.
Acetaldehyde can bind to macromolecules which the immune system recognises and attacks, sparking an immune response and causing alcohol hepatitis.
Continued alcohol excess can lead to cirrhosis.
What are the stages of alcoholic liver disease?
- Normal liver
- Steatosis (abnormal retention of lipids in hepatocytes)
- Fatty liver
- Alcoholic hepatitis (immune response, neutrophils destroy the hepatocytes)
- Cirrhosis
- Liver failure
Is there any point in the course of alcoholic liver disease that you can reverse the effects?
In the fatty liver stage, if you abstain from alcohol you can reverse the effects of fatty liver at this stage
What are mallory bodies?
Accumulation of protein bundles that are located in the cytoplasm of hepatocytes
What are 3 risk factors for developing alcoholic liver disease?
EXCESSIVE ALCOHOL CONSUMPTION (binging) Glycogen storage disease Female Acute fatty liver during pregnancy Malnutrition Obesity HIV Hepatitis C
What happens when alcohol directly affects the stellate cells in the liver?
transformed into collagen producing myofibroblast cells
