Liver and Friends Flashcards
How does the presence of fatty acids lead to the release of bile into the duodenum?
Enteroendocrine cells release cholecystokinin (CCK) which relaxes the sphincter of oddi and stimulates the gallbladder to contract
How is fat broken down in the duodenum?
Bile is a fat emulsifier
Pancreatic lipase further breaks down micelles so they can be absorbed by the villi
Give 4 risk factors for developing gallstones
Female Obesity Pregnancy Age Rapid weight loss
Where does pain occur in a gallbladder attack?
Sudden sharp pain in R upper quadrant or epigastrum which radiates to the right shoulder
Describe the pattern of pain with a gallbladder attack
Pain starts several hours after a meal and increases in severity for 15 minutes then plateaus for around 6 hours
After this it improves as the gallstone dislodges
How would you diagnose gallstones?
Recurrent symptoms
US
How would you treat biliary colic?
Manage pain and other symptoms
Cholecystectomy
Give the components of bile
70% bile salts and acids (amphiphilic components of cholesterol metabolism) 10% cholesterol 5% phospholipids 5% proteins 1% bilirubin
Give the percentage of conjugated and unconjugated bilirubin in the bile
98-99% conjugated
1-2% unconjugated
Why might cholesterol stones form?
Precipitated cholesterol due to:
Supersaturation
Not enough salts/ acids or phospholipids
Gallbladder stasis
How might bilirubin stones form?
Increased unconjugated bilirubin in bile is in anionic form due to low pH, binds to calcium ions to form calcium bilirubinate
How might brown stones form?
Bacteria such as E.coli bring in hydrolytic enzymes which hydrolyse conjugated bilirubin to unconjugated bilirubin and phospholipids to hydrolysed phospholipids which precipitate out
How can gallstones lead to acute cholecystitis?
Bile is not moving due to stone blocking the cystic duct and so acts as a chemical irritant
Mucosa in the walls starts secreting mucus and enzymes causing:
Inflammation
Distention
Pressure build-up
Give 3 types of bacteria that can cause acute cholecystitis
E.coli
Enterococci
Bacteroides fragilis
Clostridium
Describe the pattern of pain with acute cholecystitis
Pain may shift from midepigastric to R upper quadrant (dull achey pain) which may radiate to the shoulders
Positive Murphy’s sign
Describe what is meant by a positive Murphy’s sign
Pressure on the abdomen preventing abdo contents moving, patient takes a deep breath so the diaphragm pushes down on the gallbladder, if there is pain then this is a positive Murphy’s sign
How might acute cholecystitis secondary to gallstones lead to sepsis?
Increased pressure compressed the blood vessels
Gallbladder ischaemia leads to gangrenous cell death, weakening the walls which may perforate, allowing bacteria into the blood
How can gallstones in the common bile duct cause jaundice?
Bile backs up into the liver and increases pressure in the bile duct
This forces bile into the blood through narrow cell junctions and therefore increases serum conjugated bilirubin
Why would you see an increase in alkaline phosphatase in acute cholecystitis?
ALP is an enzyme found in high amounts in the liver and bile ducts
It is released by dead cells due to damage
How would you diagnose acute cholecystitis?
US:
Gallbladder wall thickening
Sludge
Distention of the gallbladder/ bile duct
Endoscopic Retrograde Cholangiopancreatography (ERCP)
Cholescintigraphy: radiolabeled marker
How would you treat acute cholecystitis?
IV fluids
pain management
Abx
Cholecystectomy
Describe chronic cholecystitis
Repeated/ constant inflammation due to gall stones repeatedly lodging/ dislodging in the cystic duct, inflammation damages the gallbladder walls
Describe the damage to the mucosa as a result of chronic cholecystitis
Pockets of mucosa rather than smooth and flat
Rokitansky-Aschoff sinus
What changes occur to the gallbladder in chronic cholecystitis?
Gallbladder becomes more sensitive
Epithelial tissue of the gallbladder can undergo fibrosis and calcification leading to a “porcelain gallbladder” usually treated with a cholecystectomy
Describe ascending cholangitis
Inflammation of the bile ducts from bacteria that travel up the duct from the duodenum
Give the medical term for gall stones in the common bile duct
Choledocholithiasis
How might the flow of bile become blocked causing ascnding cholangitis?
Choledocholithiasis
Stricture due to cancerous growth or laparoscopic injury
Give the 3 bacterial causes of ascending cholangitis
E.coli
Klebsiella
Enterococcus
How might bacteria and bile in the bile ducts, from ascending cholangitis, enter the blood stream?
Spaces between cells due to high pressure from bile build-up allows bile and bacteria into the blood
Give the 3 symptoms in Charcot’s triad for ascending cholangitis
Fever
R upper quadrant pain
Jaundice
How would you diagnose ascending cholangitis?
Blood tests: evidence of infection, jaundice and shock
Imaging:
US
ERCP
How would you treat ascending cholangitis?
Manage symptoms: Abx and rehydration
Remove the obstruction: ERCP/ shockwave lithotripsy
Widen ducts: stent
Cholecystectomy
What is the exocrine function of the pancreas?
Secrete enzymes to break down proteins, lips, carbs
What is the endocrine function of the pancreas?
Alpha and beta cells secrete hormones into the bloodstream: insulin and glucagon
How does the pancreas protect itself from self-digestion?
Enzymes are produced as zymogens stored in vesicles with protease inhibitors
How can pancreatitis occur?
Zymogens become active in the small intestine by trips
If trypsinogen is activated early it can cause acute pancreatitis as a result of acinar cell injury and impaired secretion of proenzymes
What are the two leading causes of pancreatitis?
Alcohol: thickens pancreatic juices which form plugs that block ducts, juices back up
Gallstones: blocks release of pancreatic juices
Give 5 complications of pancreatitis
Pancreatic pseudocyst Pancreatic abscess Haemorrhage from damaged blood vessels Hypovolemic shock DIC Acute respiratory distress syndrome
Give 5 signs and symptoms for the diagnosis of pancreatitis
Hypocalcaemia: used up by fat necrosis Bruising around umbilicus: Cullen's sign Bruising along the flank: Grey Turner's sign Epigastric pain radiates to back Labs: Increased serum amylase and lipase
How would you treat acute pancreatitis?
Pain management
Hydration
Electrolytes
Rest of bowels
Give 2 key causes of chronic pancreatitis
Cystic fibrosis
Repeated bouts of acute pancreatitis
Describe chronic pancreatitis
Persistent inflammation leading to fibrosis, atrophy and calcification
How would you diagnose chronic pancreatitis?
XR/ CT: calcifications
ERCP of ducts
Describe the consequences of chronic pancreatitis including symptoms
Acinar cells are impaired: loss of digestive enzymes means trouble absorbing food/ fat
This causes weight loss
Fat soluble vitamin deficiencies
Steatorrhoea
Give the 3 enzymes involved in the metabolisation of alcohol in the hepatocytes and what is the product?
CP450
Alcohol dehydrogenase
Catalase
Product: Acetaldehyde
How do levels of NAD+ and NADH vary with alcohol metabolism and how does this affect fat production in the liver?
NAD+ –> NADH when alcohol is metabolised
An increase in NADH stimulates cells to make more fatty acids
A decrease in NAD+ levels leads to less fatty acid oxidation
How can high levels of acetaldehyde lead to alcoholic hepatitis?
It can bind to macromolecules, enzymes etc. and inhibit these molecules, forming acetaldehyde adducts
This leads to the destruction of hepatocytes by neutrophilic infiltration
Give 3 signs and symptoms of alcoholic liver disease
Hepatomegaly Neutrophilic leukocytosis Perivenular fibrosis Enzymes leak out: high ALT and AST Thrombocytopenia
How would you treat alcoholic liver disease?
Stop alcohol consumption
Corticosteroids- suppress the immune system
What is the normal function of stellate cells?
Store vitamin A in the liver
What happens when stellate cells are activated by paracrine factors secreted by injured hepatocytes in cirrhosis?
They lose vitamin A, proliferate and secrete TNF-beta
and produce collagen
Describe the problems that can be caused by compression of the central veins and sinusoids due to fibrotic tissue buildup in liver cirrhosis
Portal HTN meaning fluid in the vessels is more likely to be pushed into and across tissues into space leading to:
Portosystemic shunt, renal vasoconstriction and hepatorenal failure
Ascites
Congestive splenomegaly
Explain the consequences of decreased liver detoxification in cirrhosis
Toxins can enter the brain causing hepatic encephalopathy
In particular ammonia which is usually metabolised by the liver, can cause asterixis and coma
Explain the consequences of decreased oestrogen metabolism in liver cirrhosis
Increased oestrogen in the blood can cause:
Gynecomastia
Spider angiomata
Palmar erythema
Give 3 consequences of decreased liver function other than liver detoxification and oestrogen metabolism
Decreased bilirubin conjugation
Decreased albumin production
Decreased clotting factor production
Give 4 symptoms of extensive liver fibrosis
Jaundice and pruritus
Ascites
Hepatic encephalopathy- confusion
Easy bruising
How would you diagnose liver cirrhosis?
Liver biopsy Lab test: Increased bilirubin Increased enzymes Thrombocytopenia
How would you treat liver cirrhosis?
Treat the underlying cause
Transplant
What are varices and what are they most commonly associated with?
Abnormally dilated vessels, most commonly associated with portal HTN
What symptoms may present with varices?
Vomiting
Melena
Shock
How would you diagnose varices?
Upper endoscopy
Labs: Decreased RBC count and platelets
How would you treat oesophageal varices?
Therapeutic endoscopy
Vatical ligation or banding
How does viral hepatic infection lead to liver damage?
MHC I presents the abnormal protein which attracts cytotoxic CD8+ T-cells causing cytotoxic killing and apoptosis
Give 6 symptoms of viral hepatitis
Fever Malaise Nausea Hepatomegaly Inflamed liver Pain
Which blood transaminases increase with viral hepatitis?
Alanine aminotransferase (ALT) Aspartate aminotransferase (AST)
Why is jaundice a symptom of viral hepatitis?
Conjugated bilirubin leakage from ductules into the blood
Unconjugated bilirubin cannot be conjugated by dead hepatocytes so levels in the blood increase
Why would you have dark urine with viral hepatitis?
High levels of soluble conjugated bilirubin in the urine
Why are there high levels of urobilinogen in the urine with viral hepatitis?
Bilirubin is converted to urobilinogen in the gut which cannot be converted back to bilirubin/ bile by the liver and is therefore redirected to the kidneys and excreted
What is the criteria for chronic hepatitis?
Greater than 6 months
Inflammation of the portal tract
Post necrotic cirrhosis
What is the common group at risk of acquiring HepA?
Travelers
Which antibody would be used in a HepA vaccination?
IgG antibody
How is HepC transmitted?
Childbirth, IVDU, unprotected sex
How might you test for HepC?
Enzyme immunoassay: HCV IgG
HCV RNA test (with PCR):
Early detection
Viral DNA in blood
How is HepE transmitted?
Focal-oral: undercooked seafood/ infected water
What is the risk with HepE during pregnancy?
Acute liver failure/ fulminant hepatitis
How is HepB transmitted?
Childbirth, IVDU, sex
Which types of antigens are targeted by IgG and IgM antibodies in HepB?
Surface antigen targeted by IgG
Core antigen targeted by IgM
What is the difference between chronic “healthy” and chronic infective?
Chronic “healthy” is non-replicating and less contagious
Chronic Infective: Increase in post necrotic cirrhosis and increase risk of hepatocellular carcinoma
Which strand of hepatitis must occur as a co-infection?
HepD with HepB
How does cholera cause diarrhoea?
Gram neg. bacteria produces a toxin allowing Cl- into the lumen of the intestine and water follows by osmosis
How does E.Coli 0157 bacteria cause damage?
Toxin attacks the lining of the colon causing liver and kidney damage
Where is cryptosporidium commonly found and what is it resistant to?
Protozoa commonly found in calf/ lamb faeces
Which antibiotics is C.diff associated with?
‘C abx’ e.g Clindamycin
What is C.diff resistant to and how does it cause damage?
Resistant to chlorination and alcohol
Kills top layer of the gut lining which starts to slough off
Where are the common places to acquire norovirus and at which time of year?
Hospitals, schools, cruise ships
Mainly during winter
Give 6 symptoms of norovirus
Vomiting, diarrhoea, nausea, cramps, headaches, fever
Describe the Bristol stool scale
1-7, 1: separate hard lumps, 3-4 is normal, 7:liquid
Roughly how much copper do we consume in the diet each day and how much of this is needed?
Consume 1-2mg/day
Need about 0.75mg/day
What happens to excess copper in the body?
90% bile (faecal copper)
10% urine
In Wilson’s disease, what happens to excess copper in the body?
It is converted to Cu2+ + OH- + hydroxide free radical
How is copper usually absorbed and exocytosed to bile?
Absorbed by enterocytes and carried to the liver where, though ATP7B, it either binds to ceruloplastimin or is packaged into vesicles for exocytosis to bile
How does copper buildup inside the hepatocytes in Wilson’s disease?
There is an autosomal defect in the ATP7B gene meaning copper cannot bind to ceruloplastin or be packaged into vesicles, so it builds up and produces free radicals
In Wilson’s disease, what can occur if copper deposits in the following locations:
Basal ganglia
Cerebral cortex
Descemet’s membrane
Movement disorder
Dementia
Kayser-fleishcher rings
What would the blood test results be for Wilson’s disease?
Low ceruloplasmin
High free Cu in the blood and urine
How would you treat Wilson’s disease?
Penicillamine (copper-chelating agent)
Meds to decrease Cu reabsorption
Liver transplant
What is the key role of alpha-1 antitrypsin?
Inhibiting the action of elastase on elastin
Give 4 symptoms of alpha-1 antitrypsin deficiency in the lungs
SOB, wheezing, mucous production, cough
Give 5 signs and symptoms of alpha-1 antitrypsin deficiency in the liver
Inability to make coagulant factors, buildup of toxins, oesophageal variecs (portal HTN), hepatocellular carcinoma, jaundice
How would you diagnose alpha-1 antitrypsin deficiency?
CXR/ CT: hyperinflation/ damaged tissue
Pulmonary function
Blood test
If suspected cirrhosis: liver US/ biopsy
How would you treat alpha-1 antitrypsin deficiency?
Augmentation therapy IV infusion of normal A1AT protein: slows/ halts progression Supplemental O2 Inhalers Standard treatment for cirrhosis
Where is the most common place for a liver malignancy to metastasise to?
Lungs
Where do secondary hepatic tumours often originate from?
Colon
Pancreas
Lungs
Breast
Give 5 causes of liver cirrhosis which can lead to malignancy
Alpha-1 antitrypsin deficiency Alcoholic hepatitis Primary biliary cirrhosis Haemachromatosis HBV and HCV
How can aspergillus moulds cause liver malignancy?
Toxins produced are metabolised in the liver and form a DNA adduct, causing a mutation in the P53 tumour suppressor gene
What is Budd-Chiari syndrome?
Liver tumour has spread to portal and hepatic veins
The veins are blocked, increasing pressure in the portal system causing ascites and hepatomegaly
What proportion of liver cancer is asymptomatic? Give 2 potential symptoms
1/3 asymptomatic
Fever
Abdominal pain
What blood test results might you see with liver cancer?
High AFP (produced by tumour cells)
High ALP and GGT (liver enzymes released with damage)
High erythropoietin
High insulin-like GF
How would you diagnose liver cancer?
CT/ US
Angiography to see tumour vascularity
How would you treat liver carcinoma?
20% are surgically removable
Transplant
Where are 95% of pancreatic tumours found?
Exocrine glands, mainly the epithelial cells lining the ducts
Where are 5% of pancreatic tumours found?
Acinar cells
Give 3 modifiable and 3 non-modifiable risk factors for pancreatic cancer
Smoking
Obesity
Diet high in red meat
Male
Afro-caribbean
>65y/o
Give 3 diseases associated with pancreatic cancer
Diabetes
Chronic pancreatitis
Liver cirrhosis
Give 2 genes which may predispose someone to pancreatic cancer
BRCA2
PALB2
Give 5 symptoms of pancreatic cancer
Nausea Vomiting Fatigue Weight loss Midepigastric pain: radiates to mid/ lower back, worse when lying flat
What is Trousseau’s sign of malignancy?
Blood clots felt as small lumps under the skin
What is Courvoisier sign in pancreatic cancer?
Gallbladder enlarged and palpable but not tender
What problems may arise if there is a tumour in the head of the pancreas?
It may obstruct the common bile duct and cause obstructive jaundice
Give 4 symptoms of obstructive jaundice
Loss of appetite
Darker urine
Lighter stools
Pruritis
How would you stage pancreatic cancer?
1: <2cm
2: >2cm
3: grown into neighbouring tissue
4: metastases
How would you treat pancreatic cancer?
Surgery and adjuvant chemotherapy
Give 3 causes of ascites
Low protein (can't pull fluid into vessels) Local inflammation (= more fluid) Low flow (fluid can't move through system therefore causing an increase in pressure)
Give 2 causes of low protein which then causes ascites
Malnutrition
Hypoalbuminaemia
Give 2 causes of local inflammation which then causes ascites
Peritonitis
Abdominal cancers
Give 3 causes of low flow which then causes ascites
Cardiac failure
Cirrhosis
Constrictive pericarditis
Give 3 features of ascites you may find on examination
Distended abdomen
Dull percussion
Scratching= jaundice
How would you diagnose ascites?
Ascitic tap
USS
What is the difference between transudate and exudate ascitic fluid and when would you find either one?
Transudate (<30g/l) Cirrhosis Constrictive pericarditis Cardiac failure Hypoalbuminaemia
Exudate (>30g/l)
Malignancy
Peritonitis
Pancreatitis
Give 2 causes of peritonitis
Bacteria: Gram +ve (Staph)
Gram -ve (Coliforms)
How would you differentiate between parietal and visceral peritonitis?
Parietal (abdo wall)- well localised pain
Visceral (organs)- poorly localised
Where would you get pain with peritonitis of the:
Foregut
Midgut
Hindgut
Epigastric
Periumbilical
Suprapubic
Give 3 typical findings in a history of a patient with peritonitis
Sudden onset
Pain lying stil
Improve when apply pressure
Speedbumps hurt
How would you diagnose peritonitis?
Bloods: signs of infection/ inflammation/ amylase/ low Hb
CXR: air under diaphragm = perforation
Abdo XR: foreign body/ intestinal block
CT: Ischaemia/ cancer
How would you treat peritonitis?
ABC
Treat underlying cause
What is an inguinal hernia and what is it associated with?
Fatty tissue/ bowel pokes through into your groin at the top of the inner thigh
Associated with ageing and repeated abode strain
Which type of hernia is more common in men and which in women?
Inguinal: men
Femoral: women
What is an umbilical hernia and how can it occur in neonates?
Fatty tissue/ part of bowel pokes through near naval
In neonates, the opening through which the cord passes may not seal properly after birth
What is a hiatus hernia and what symptom may it cause?
Part of the stomach pushes up through an opening in the diaphragm
Can cause heartburn
If strangulation/ obstruction occurs due to a hernia which symptoms can it cause?
Sudden/ severe pain
Vomiting
Constipation
How would you treat a hernia?
Surgery
