Gastrointestinal Flashcards
general anatomy of liver
- Large, lobated exocrine and blood-processing gland, with vessels and ducts entering and leaving at the porta.
- Enclosed by a thin collagen tissue capsule, mostly covered by mesothelium.
- Collagen tissue of the branching vascular system provides gross support.
- Parenchymal cells are supported by fine reticular fibres
blood supply of liver
The portal vein brings 75% of blood (filled with nutrients) to the liver while the hepatic artery (oxygenated blood) brings 25%.
nerve supply of liver
sympathetic & parasympathetic supply of perivascular structures but very little at sinusoidal level
hepatic lobule structure
consists of hexagonal plates of hepatocytes stacked on top of each other. Within each plate, the hepatocytes radiate outwards from a central vein
Hepatic sinusoids travel between the strips of hepatocytes, draining into the central vein
hepatic lobule structure
There are hepatic lobules in each segment of the liver. They are formed from hexagonal shapes and in each corner there is a hepatic artery, portal vein and a bile duct. In the middle there is a central vein for drainage.
Hepatic sinusoids travel between the strips of hepatocytes, draining into the central vein
types of liver blood vessels
a) Central vein / terminal hepatic venule - very thin wall; lies in the centre of a lobule, with sinusoids converging towards and opening into it.
(b) Sublobular/intercalated vein - thicker wall; lies alone at the periphery of the lobule.
(c) Branch of portal vein - again at the periphery of the lobule, but accompanied by one or more small hepatic arteries/arterioles, one or more bile ducts/ductules lined by cuboidal epithelium, and lymphatics.
Hepatic lobular blood flow is:
(a) from branches of the portal vein and hepatic artery; from the periphery towards the centre (mixed so blood is oxygenated and rich in nutrients)
(b) in the sinusoids, between the cell plates.
(c) Blood collected in central veins goes to sublobular veins, then to collecting veins, and then hepatic veins leaving the liver.
Rappaport’s liver acinus=
functional unit comprising parts of three or so lobules.
tries to explain differences in exposure to the blood supply among various parts of lobules.
Such differences are reflected in varied functional activities and degrees of susceptibility to toxic agents - a metabolic zonation.
Acinus territories
• 1 periportal
• 2 intermediate
• 3 perivenous (close to the central vein) zones, with the initial periportal zone being roughly spheroid, and isolated from periportal zones of adjacent acini.
Acinus with different areas of metabolic function of hepatocytes
where are undifferentiated stem cells in the liver?
In the periportal area, there are more undifferentiated stem cells that are ready to differentiate if there is evidence of liver damage.
Sinusoids =
low pressure vascular channels that receive blood from terminal branches of the hepatic artery and portal vein at the periphery of lobules and deliver it into central veins
what are liver sinusoids lined by?
fenestrated endothelial cells, loosely attached and rest on microvilli of underlying hepatic cells, without a basal lamina intervening
what do sinusoids hold?
hold phagocytic Kupffer cells (larger, stellate, with a pale oval nucleus)
Space of Disse
- Plasma can pass through the sieve plate, formed by the lining cells, out into the perisinusoidal space of Disse to interact with the hepatocytes. Some of this fluid may pass to the periphery of the lobule to be collected as lymph.
- Disse’s ‘space’ contains ECM materials, but not a visible basal lamina.
hepatic sinusoid detoxification process
- Sinusoids are lined by highly specialised fenestrated liver sinusoidal endothelial cells (LSECs) which maintain blood cells in the sinusoid but allow passage of substances (<200 nm) and exosomes into the space of Disse
- Process ensures exposure of these particles to hepatocytes and stellate cells within the space of Disse, allowing hepatocytes to perform their crucial role within the liver of maintaining metabolic homeostasis, storing nutrients, secreting bile and detoxifying drugs
hepatocytes structure and arrangement
The cells are polygonal in shape and their sides can be in contact either with sinusoids (sinusoidal face) or neighbouring hepatocytes (lateral faces).
- A portion of the lateral faces of hepatocytes is modified to form bile canaliculi. Microvilli are present abundantly on the sinusoidal face and project sparsely into bile canaliculi.
- Hepatocyte nuclei are distinctly round, with one or two prominent nucleoli, majority of cells have a single nucleus, but binucleate cells are common
liver cirrhosis pathophysiology
many inflammatory cells circulate the sinusoids, the Kupffer cells get activate and stellate cells get activated and produce collagen
Fenestrations start closing up because of collagen deposition sinusoidal pressure builds up many hepatocytes die, other hepatocytes are surrounded by fibrous tissue (all gates close)
liver lymphatic system
- Lymph is formed by filtration of plasma into the spaces of Disse as blood flows through the sinusoids.
- Then lymph percolates between the space of Disse and portal tracts then lymphatics are formed that run along portal vessels and biliary ducts.
bile pathway
Bile caniculi join together to form bile ductules → bile ducts in portal tracts in periphery of lobule → intrahepatic bile ducts that join to form hepatic ducts leaving each lobe
bile duct epithelium
- Bile ducts’ epithelium changes to columnar mucous cells and, extrahepatically, the ducts acquire smooth muscle as well as collagen tissue.
when does the cystic duct allow bile reflux into the gallbladder?
- Cystic duct allows reflux into the gallbladder, when sphincter of Oddi at the duodenal outlet of the common bile duct is closed.
microbial food poisoning
acute gastroenteritis due to eating (or drinking) food containing microorganisms or their toxic products
characteristics of campylobacter species
microaerophilic, gram negative curved rods, grow well at 42°C
C. jejuni and C. coli food poisoning
- Associated with poultry (frozen), wild birds and other animals- milk and water
- Sporadic
- Incubation: 24-72h, duration: 1 week
- Symptoms: diarrhoea, sever stomach cramps
Rare but significant cause of Guillain-Barre Syndrome (peripheral neuropathy)
Non-typhi Salmonella spp food poisoning
- Associated with poultry/eggs
- Sporadic and outbreaks
- Incubation: 6-48h, duration: 1-7 days
- Often serious: fever, diarrhoea, vomiting
Clostridium Perfringens food poisoning
- Associated with bulk cooking of meat
- Often large outbreaks.
- Incubation: 8-22h; duration: 1-2 days
- Severe abdominal cramps with diarrhoea
- Warm food - contamination by spores which germinate
pathophysiology of Clostridium Perfringens
- A culture of vegetative bacteria is ingested
- Bacteria sporulate in small intestine and produce an enterotoxin
- Destruction of villus tips with resultant pain and diarrhoea
toxins of common food poisoning agents
- Botulism= neurotoxins
- Staphylococcal enterotoxins= classic superantigens
- Bacillus cereus enterotoxins
- Mycotoxins
- Paralytic shellfish intoxications
Clostridium Botulinum food poisoning
- Anaerobic, spore-forming, types A-G
- Widely distributed in nature
- Produces the most powerful natural toxin (1mg lethal for 200000 mice or one human)
- Causes classical food-borne intoxication (Botulism), rare wound botulism, infant botulism and equine grass sickness
Staphylococcus Aureus food poisoning
- Common skin organism
- Contaminates salted foods and dairy produce
- Incubation: 2-6 h; Duration: 1-24 h
• Very acute vomiting response often followed by diarrhoea
• Staph enterotoxins are bacterial superantigens
Bacillus Cereus food poisoning and pathophysiology
- Often associated with cooked rice
- Acute vomit response followed by diarrhoea
- Incubation: 1-5 h; Duration: 12-24 h
• Spore germinate in warm cooked rice
• Toxin produced
• Heat stable, survives re-cooking
• Separate toxins for vomiting and diarrhoea responses
Norovirus food poisoning- small round-structured viruses
- Sporadic
- Usually spread directly, but some outbreaks associated with shellfish (filter feeders/sewage contamination)
- Vomiting, diarrhoea, low grade fever
- Incubation: 48h; Duration: 1-2 days
Escherichia Coli forms of GI pathogen
- ETEC Enterotoxigenic E. coli (similar to V. cholerae CT=EcLT)
- EPEC Enteropathogenic E. coli (most common)
- EIEC Enteroinvasive E. coli
- EHEC Enterohaemorrhagic E. coli
- VTEC Verotoxin-producing E. coli
Routes of transmission of EHECs:
- Food-borne (faecal contamination)
- Faecal-oral
- Environmental contamination by domestic animals
EHECs are highly infectious agents - Infectious dose= ~10 bacteria
pathophysiology of escherichia coli
Attachment and effacing lesion and TTSS
- Typical of EPECs
- Requires product of eae gene: intimin which allows organism to bind to cells
- Destruction of microvilli of enterocytes
- Pedestal formation due to accumulation of polymerized actin.
- Type III secretion system
- Diarrhoea
Enterocyte attaching and effacing lesions of Escherichia Coli
The organism located on the border of microvilli in the villus and attach and efface the microvilli to form a pedestal where the organism sits on a pedestal of actin and fibrin.
virus general pathogenesis
- Are not able to replicate by themselves but require host cells and its cellular biochemiacal machinery to generate progeny
- Attach to host cell using receptor-binding proteins targeting host cell surface molecules that also serves as virus specific receptors
clinical symptoms of hepatitis
- Yellowing of skin and eyes (jaundice)- there can be other causes of jaundice
- Dark urine
- Clay-coloured stool
- Nausea and vomiting
- Loss of appetite
- Fever abdominal pain
- Weakness
transmission of Hep A & E
- transmitted faecal-oral (via stool into water and then consumed), have to be more persistent so don’t have envelopes
HEP B, C & D transmission
- transmitted parenteral, can cause chronic infections, stays in body after primary infection, can be treated (typically B & C), enveloped (more sensitive)
who can Hep D infect?
Hep D can only infect people who are Hep B+= coinfection or superinfection
Hepatitis A
- Non-enveloped ss+ve RNA picornavirus
- At least 6 major genotypes, I-VI ( type I is prevalent worldwide)
- Incubation time= 10-50 days
- Primarily children and young adults
- No seasonality
- Fecal-oral transmission, liver enzymes increase dramatically
- Abrupt onset, commonly with pyrexia
- Resolves spontaneously (without chronicity i.e no carrier state) followed by lifelong immunity
- Fatality rate <0.5% in icteric (permanent liver failure) cases- increase in age increases mortality
Markers in Hep A Course of Infection
- IgM antibody to HAV in blood indicates recent HAV infection and persists for up to 4-6 months post infection
- HAV RNA in blood is present at the onset of symptoms/signs
- Anti-HAV IgG in blood indicates HAV infection (or vaccine response), detectable by onset of symptoms/signs and persists for life
where is HAV mainly prevalent?
HAV is mainly prevalent in Sub-Saharan African and South Asia (India).
Hepatitis B
- Enveloped partially dsDNA hepadnavirus
- At least 8 main genotypes (type A is most prevalent in Europe)
- Incubation time= 40-180 days
- Primarily babies and young adults
- No seasonality
- Parenteral, vertical (mum to the foetus), sexual transmission (close contact)
- Insidious onset, sometimes apyrexial
- Virus remains in hepatocytes for life and may re-activate under immunosuppression (anti-HBcAb IgM may become detectable again)
- Chronic infection (carrier state) develops in 5-10% of adults (95% of neonates) and is associated with hepatocellular cancer
- Up to 2% fatality rate in icteric cases
treatment for chronic infection of Hep B
Treatment (for chronic infection): interferon alpha or antivirals (eg. tenofovir, entecavir), HBsAg seroconversion will occur in a small proportion of cases treated with interferon alpha but is even less likely to occur with antivirals (are very effective in suppressing virus replication)
Recombinant HBV surface antigen vaccine
- glycoprotein on the envelope (and immunoglobulin) available, neutralising antibodies are able to prevent infection, 95-98% efficient
There are non-responders who do not develop protective surface antibodies
Hepatitis B surface antigen (HBsAg)
- Found in HBV envelope and indicates active HBV infection found in serum during acute and chronic (carrier) state infection
- Anti-HBsAg (antibody) Indicates past HBV infection or immune response to HBV vaccine or passive antibody transferred following administration of HBV Ig
Hepatitis B core antigen
- Part of the HBV nucleocapsid
- Anti-HBcAg IgM (IgM antibody to core) Indicates a recent HBV infection and persists for four- six months post infection
- Anti-HBcAg IgG Indicates recent or past infection with HBV and is detectable by onset of acute symptoms and persists for life
Hepatitis B E Antigen (HBeAg)
- Associated with HBV nucleocapsid and indicates active HBV infection
- The antibody indicates HBV seroconversion
Hepatitis C Virus
- Enveloped in ss+ve RNA flavivirus
- At least six main genotypes (type 1 & 2 are prevalent in Europe)
- incubation time is 15 to 160 days
- primarily adults
- no seasonality
- parenteral transmission (sexual route)
- acute phase often very completely asymptomatic
- chronic infection established in 70 to 90% of cases, chronic infection (carrier state) is associated with hepatocellular cancer
- up to 1% fatality rate in icteric cases
treatment of Hep C
- treatment: interferon alpha together with ribavirin or direct acting antivirals (DAAs) such as protease inhibitors (eg. boceprevir, telaprevir) and/or polymerase inhibitors (sofosbuvir)
- increasingly, with advent of DAAs, HCV is fast becoming largely curable (>90% [genotype independent]) infection
markers over course of Hep C infection
- Anti HCV antibodies which indicate recent and or past HCV infection and take up to three months to develop
- HCV antigen reflects viraemia (active infection)
- HCV PCR determines viraemia and thus whether the infection is an active one (which requires treatment): success depends on genotype
- IL28B genotype (single nucleotide polymorphism)- helped to determine susceptibility to antiviral therapy but is of reduced/limited use now
Hepatitis D Virus
- Enveloped circular ss-ve RNA
- At least three major genotypes type one is most prevalent worldwide
- similar to HBV envelope contains HBsAg
- defective virus that needs HBV for replication
- Co infection with HBV: severe acute disease, low risk of chronicity
- superinfection on chronic HBV infection- chronic HDV infection and high risk of severe chronic liver disease
Hepatitis E Virus
- Non-enveloped ss+ve RNA hepevirus
- 7 genotypes (1-4 in humans, type 1&2 cause outbreaks in humans and type 3&4 are also found in animals (swine, deer), type 3 found worldwide)
- Faecal oral transmission
- incubation time 15 to 60 days
- overall fatality rate is 1 to 3% but 15 to 25% in pregnant women in outbreaks: HEV genotype 1
- No chronicity identified except in the immunocompromised
- probably endemic in Europe but underdiagnosed
what provides protection against HDV?
HBV vaccination provides indirect protection against HDV
treatment of HEV
- no vaccine (HEV genotype 1 vaccine available in China)
- treatment= supportive, ribavirin can be used to treat chronic infection
HAV treatment and vaccine
- Inactivated virus vaccine (and immunoglobulin) available
- Treatment= supportive
Other viral Causes that can also cause Hepatitis:
- Non-A/E hepatitis
- Epstein-Barr virus (EBV)
- Cytomegalovirus
- Herpes simplex virus type ½
- Rubella virus
- Enteroviruses
- Yellow fever viruses
functions of the liver
detoxification, protein synthesis, energy storage
Failure to clear bilirubin-> Failure to clear gut derived toxins (NH3) ->
Failure to clear bilirubin jaundice
Failure to clear gut derived toxins (NH3) encephalopathy
Failure to produce clotting factors ->
Failure to produce clotting inhibitors ->
Failure to produce albumin ->
Failure to produce clotting factors coagulopathy on blood tests
Failure to produce clotting inhibitors lack of balance in clotting
Failure to produce albumin oedema, impaired binding of drugs
Failure to store or release glucose ->
Failure to utilise carbohydrate ->
Failure to store or release glucose hypoglycaemia
Failure to utilise carbohydrate muscle breakdown
time scale of acute vs chronic liver failure
- Time scale: <2-3 months vs >2-3 months
acute liver failure=
- Rapid onset with no underlying chronic liver disease
uncommon and rare presentation of acute liver failure
- Severe acute liver injury +jaundice = high ALT UNCOMMON
- Acute liver failure + jaundice/coagulopathy
+ encephalopathy = high ALT RARE
common presentation of acute liver failure
- Acute liver injury= high alanine aminotransferase (ALT)
causes of ALF
common case of ALF is paracetamol. Less common causes include:
- Other drugs
Antibiotics esp. anti-TB meds
- Ecstasy
- Acute viral infections -hepatitis B (and A, E)
- Autoimmune hepatitis
- Seronegative (non-A to E) hepatitis
Correction of Coagulopathy in ALF
- Vitamin K (for Koagulation
- Substrate required for certain clotting factor synthesis (II, VII, IX, X dependant on Vit K)
- If dietary deficiency, clotting will look worse than liver function really is, so give them Vit K
- Replacement will not ‘mask’ liver dysfunction as it won’t be able to use the Vit K - FFP (fresh frozen plasma)
- Blood product containing clotting factors
- Replacement will prevent use of clotting times as a marker of liver function so try to avoid giving it
Prognosis in Paracetamol ALF
The patient is unlikely to recover spontaneously if:
- PT> 100 AND
- Anuric/ creatine >300 AND
- Grade 3-4 encephalopathy (stupor/coma)
Prognosis in Non-paracetamol ALF
- Age (<10 or >40 worse)
- Aetiology (drug/seronegative worse than viral)
- PT>50 or INR>3.5
- Bilirubin >300
- Time from jaundice to encephalopathy <7d
3/5= unlikely to recover spontaneously
Paracetamol vs Non-Paracetamol ALF
Paracetamol causes hyper acute liver failure
- Rapid progression of coagulopathy over hours rather than days
- Usually encephalopathy in less than 1 week
Other causes usually have a more gradual onset, progression over several weeks.
ALF Management
- Identify and treat the underlying cause • N-acetyl cysteine for paracetamol • Antivirals for hepatitis B • Steroids for autoimmune hepatitis - Supportive care - Close monitoring (esp paracetamol) - Liver transplantation if appropriate
chronic liver failure
Impaired hepatocyte function: jaundice, coagulopathy, low albumin
liver failure causes hepatic encephalopathy: features and triggers
Features: - Failure of hepatocyte function (NH3 clearance) - Portosystemic shunting Triggers: - Constipation - Drugs- opiates, sedatives - Dehydration- diuretics - Infections - GI bleeding
ascites causes
low albumin, portal hypertension or renal hypoperfusion
Causes of CLF are
generally any cause of cirrhosis:
- Alcohol
- Non-alcoholic fatty liver disease
- Hepatitis B or C
- Haemochromatosis
- Wilson’s Disease
- Primary biliary cholangitis
- Primary sclerosing cholangitis
- Autoimmune hepatitis
CLF management
- Identify and treat underlying cause • Abstinence for alcohol • Antivirals for hepatitis B/C • Steroids for autoimmune hepatitis - No treatment for jaundice - Low salt diet and diuretics for ascites - Laxatives and antibiotics for encephalopathy - Liver transplantation if appropriate
glucose metabolism in fasting
• ↓ insulin and ↑ glucagon from pancreas → normoglycaemia
- Glycogen breakdown in periportal hepatocytes
• Major glucose store in body
• Gluconeogenesis from: lactate, pyruvate, amino acids and glycereol
glucose metabolism in feeding
• ↑ insulin and ↓ glucagon → hepatic glucose uptake
- Glycogen deposition in hepatocytes
Phase 1 Metabolism of drugs in liver
oxidation, reduction and hydrolysis reactions
Inactivating the drug and making it water soluble for excretion
hepatic synthesis of cytochrome P450 is increased by some classes of drug- enzyme induction, can increase the rate of phase 1 reactions
Phase 2 Metabolism of drugs in liver
Phase 2 conjugation reactions: These reactions include glucuronidation, sulphation, acetylation and methylation amongst others. Conjugates are almost always pharmacologically inactive, more water soluble and easily exerted in urine/bile.
conjugation with glutathione - major pathway for drug detoxification
stellate cells function
storage and transport of retinoids (vitamin A compounds)
cytochrome P450 system in Phase 1
employs P450 to NAPQI (toxic byproduct of paracetamol) in overdose
overdose reversal of paracetomol
Glutathione-S-transferase is capable of detoxifying NAPQI to mercapturic acid if GSH is available
•N-acetylcysteine is a source of glutathione substrate
phase 3 metabolism of drugs
secretion into the bile, exertion is mediated by ATP
proteins synthesised by the liver
- Albumin
- Transport proteins
- Caeruoplasmin and Transferrin- transport of copper and iron
- Ferritin- iron storage
- Protease inhibitors
- ɑ1 antitrypsin- lead to liver disease
- CRP- marker of inflammation, in liver dysfunction it may not make enough so not perfect marker
- AFP- rise in AFP may alter to presence of hepatocellular carcinoma
- Complement
- Coagulation factors- Fibrinogen, II, V, VII, IX and X
bile is made up of
600ml of bile per day is made up of:
• Bile acids primary (made in liver) and secondary (absorbed): allow digestion of dietary fats through emulsification
• Phospholipids
• Cholesterol
• Conjugated drugs
• Electrolytes: Na+, Cl-, HCO3- and copper
• Bilirubin
bilirubin production
Haem is a breakdown product of RBCs and it gets converted to unconjugated bilirubin. In the liver it is conjugated with glucuronic acid. Conjugated bilirubin is converted to urobilinogen and some of it is converted to stercobilin (gives stool the brown colour), some is reabsorbed and some is absorbed into blood and kidneys convert urobilinogen to urobilin and excrete it in the urine.
bile duct obstruction stool
In bile duct obstruction you can have floaty stool and pale stool as bilirubin is needed for the brown colour.
absorption of bilirubin
Conjugated bilirubin is not absorbed but bile is deconjugated in small bowel and colon. These are more hydrophobic.
storage of vitamins in liver
- Vitamin A, D and B12 are stored in large amounts
- Small amounts of Vitamin K and folate are rapidly depleted with decreased dietary intake
- Metabolises cholecalciferol vitamin D3 → activated 25-(OH) vitamin D
minerals stored in liver
- Iron stored in ferritin and haemosiderin
* Copper
immunological function of liver
• “firewall” filtering all blood from gut- first line of defense against pathogens absorbed from the gut
• Kupffer cells phagocytose pathogens from gut
• Supply of important chemokines:
o Interleukins
o Tumour necrosis factor
• Priming T cell responses
liver cirrhosis definition
• Development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury
→ portal hypertension and end stage liver disease
cause sof liver cirrhosis
- Viral infection o Hepatitis B and C - Alcohol - Non Alcoholic Steato-Hepatitis - Autoimmune disorders o AIH (autoimmune hepatitis) - Cholestatic liver disease o PBC (primary biliary cholangitis) and PSC (primary sclerosing cholangitis) - Metabolic causes
reversal of fibrosis
Fibrosis is reversible through removal of underlying cause or antifibrotic drug/ cell therapy.
cirrhosis formation from fibrosis and risk
if insult continues you can have disrupted architecture, loss of function and aberrant hepatocyte regeneration which leads to cirrhosis. Current treatment= liver transplant as cirrhosis is not reversible, with cirrhosis you have higher risk of hepatocellular carcinoma
hepatocyte injury
Whatever the cause of injury, it leads to apoptosis of hepatocytes and this leads to recruitment of activated macrophages and activation of hepatic stellate cells.
fibrosis pathology
Inflammatory recruitment of dying hepatocytes leads to the secretion of pro-inflammatory and fibrotic mediators which encourage differentiation of stellate cells to activated myofibroblasts and fibroblasts to myofibroblasts too. These lead to matrix synthesis with a-SMA and collagen 1 leading to matric deposition, the whole process results in a reduction in matrix degradation. By removing cause of injury, there can be decreased activity of pro-inflammatory cytokines which increases MMPs and results in matrix degradation and loss of myofibroblasts.
stellate cells in liver fibrosis and cirrhosis
Very potent in generation of fibrosis and cirrhosis. Activation of quiescent stellate cell and portal/perivascular fibroblast to make myofibroblast which leads to increased collagen production and decreased MMPs collagen accumulation
sequence of collagen deposition
- myofibroblasts increased 10x increasing type 1 & 3 fibrillar collagen
- decreased metabolite and oxygen exchange across space of Disse > hepatocyte dysfunction
- increased angiogenesis, sinusoidal remodelling
- increased sinusoidal resistance and portal hypertension
portal hypertension leads to:
- Formation of portosystemic collaterals- blood can pass from portal circulation to systemic without being filtered by liver
- Varices- extra BVs around oesophagus and stomach which can lead to bleeding
- Portal venous blood inflow- worsens portal hypertension
- Splanchnic vasodilation
- Increased risk of HCC
diagnosis of fibrosis/cirrhosis (pros and cons)
- Liver biopsy
✓ Gold standard, quantative
✕ Sampling error, morbidity - Serum markers
✓ Widely available, non-invasive
✕ Nonspecific, grey zone for intermediate fibrosis - Elastography
✓ Non-invasive, fast and user friendly, validated in chronic hepatitis
✕ Cost, confounding factors (body habitus)
Fibroscan (elastography)- liver should be like jelly but as fibrosis increases then the liver becomes more solid, the probe can measure this
serum markers of liver cirrhosis
- Albumin
- Decreases in end-stage liver disease due to decreased synthesis
- T1/2: 20 days therefore useful in cirrhosis
- Prothrombin time
- Decreased synthesis of clotting factors (I, II, V, VII, X) →↑ PT
- In cirrhosis associated with more advanced disease
- Bilirubin
- Increased in end stage cirrhosis due to decreased clearance
- Platelets
- Decreased in cirrhosis
- Splenomegally →↑ consumption
- Decreased Thrombopoietin production by cirrhotic liver
child-pugh scores
Child-Pugh scores can be used to assess risk and mortality by categorising patients into class A, B or C.
excretion of bilirubin in the bile
The water-soluble conjugated bilirubin is excreted in the bile which travels through the small intestine to the bowel.
pre-hepatic jaundice
In pre-hepatic jaundice, the level of unconjugated bilirubin increases and it exceeds the ability of the liver to conjugate. As it is water insoluble, it does not enter the urine. Eg. Haemolysis, Glucoronyl transferase deficiency (Gilbert’s), 10% of the population
hepatic jaundice
In hepatic jaundice, there is damage in the hepatocytes meaning that the liver cannot take up bilirubin nor can it conjugate it.
causes of hepatic jaundice
Caused by: o Viruses – hepatitis, CMV, EBV o Drugs: paracetamol, anti-TB, o Alcohol o Cirrhosis, autoimmune diseases o Sepsis o Right heart failure
post hepatic jaundice
In post hepatic jaundice, conjugated bilirubin spills out into the bloodstream and is excreted by the kidney. Symptoms of this is pale stool, dark urine and itch (bile salts that can’t get through so end up in skin). This can be caused by obstructive jaundice.
classification of causes of post hepatic jaundice
Classification of causes: within the lumen (gallstones), within the wall (cholangiocarcinoma), external compression
Whipple operations
Whipples are operations where the gallbladder, distal bile duct, duodenum, part of the stomach are removed and pulling up the jejunal end to join everything back together.
Option for people with pancreas cancers and distal bile duct cancers.
examination for jaundice
• Peripheral stigmata of liver disease: finger clubbing, palmar erythema, Dupuytren’s, sclera for jaundice, Virchow’s nodes, spider naevi, gynaecomastia • Hepatomegaly • Splenomegaly (portal hypertension) • Ascites • Palpable Gallbladder
treatment of jaundice underlying causes
Treat underlying causes:
o Pre-hepatic: stop haemolytic process
o Hepatic: anti-virals, prevent deterioration of cirrhosis, eg alcohol, drugs
o Obstructive causes: ERCP/stenting, surgery, palliation
treatment of jaundice symptoms
Treat symptoms: o Analgesia o IVI o Antibiotics if septic o Vitamin K & chlorphenamine
clinical presentation of gallstones
- RUQ or epigastric pain
- Colicky or constant
- Dyspepsia, nausea, vomiting
- Biliary colic
- Obstructive jaundice
- Acute cholecystitis (inflammation of gall bladder)
- Acute pancreatitis
