Liver & Gall bladder Flashcards
Which veins make up the hepatic portal vein?
- Superior Mesenteric Vein
- Splenic Vein
- Inferior mesenteric
The portal vein carries outflow from?
- ) Spleen
- ) Oesophagus
- ) Stomach
- ) Pancreas
- ) Small and large intestine
How much blood does the hepatic portal vein supply to the liver?
75%
Hepatic Blood Flow
- Oxygenated blood from hepatic artery & nutrient-rich, deoxygenated blood from hepatic portal vein
- –> Liver sinusoids
- –> Central vein
- –> Hepatic vein
- –> IVC
- Right atrium
Portal-caval anastomoses
4 collateral pathways
- Esophageal and gastric venous plexus
- Umbilical vein from the left portal vein to the epigastric venous system
- Retroperitoneal collateral vessels
- Hemorrhoidal venous plexus
What may happen to the portal caval anastomoses?
In portal hypertension, the collateral vessels may become engorged, dilated or varicosed.
May rupture
Normal pressure of the portal vein system?
5-8 mmHg
PORTAL HYPERTENSION
- Pressure above normal range of 5-8mmHg
- Portal vein-hepatic vein pressure gradient greater than 5mmHg
- Represents increase in hydrostatic pressure within portal vein and its tributaries
Portal Hypertension - Causes
- Prehepatic
- Intrahepatic
- Prehepatic -
Blockage of the portal vein before the liver, due to portal vein thrombosis or occlusion secondary to congenital portal venous abnormalities
- Intrahepatic -
Due to distortion of the liver architecture
i. PRESINUSOIDAL - schistosomiasis; non cirrhotic portal hypertension
ii. POSTSINUSOIDAL - cirrhosis, alcoholic hepatitis, congenital hepatic fibrosis
3. Budd-Chiari and veno occlusive disease
Budd-Chiari syndrome
Thrombosis/Occlusion of the hepatic veins draining the liver
> Congenital webs
Thrombotic tendency, protein C or S deficiency
Clinical//
• Acute
– jaundice, tender hepatomegaly
• Chronic
– Ascites
Abdo pain, ascites and liver enlargement
Diagnosis//
– US of hepatic veins
Treatment//
- Recanalisation
- TIPSS
Wilson’s Disease
- Disorder of copper metabolism
- Loss of function or loss of protein mutations in CAERUOPLASMIN
- Copper-binding protein, loss of copper regulation
- massive tissue deposition of copper
Clinical //
- Neurological (involuntary movements)
- Hepatic (cirrhosis)
- KAISER-FLEISCHER Rings
- Basal ganglia degeneration
- Dementia
- Blue nails
- Chromosome 13
Treatment//
copper chelation drugs - PENICILLAMINE
ZINC
Hepatic Carcinogenesis
- Recurrent hepatocyte death
- regeneration
- cellular hyperplasia (recurrent DNA copying)
-INFLAMMATION
degranulation cell cycle control
DNA damage due to ROS & RNS
Cirrhosis
- Compensated
- Decompensated
i) Compensated
- clinically normal
- incidental finding
- lab test/ imaging abnormality
- Portal Hypertension may be present
ii) Decompensated
- Liver Failure > acute on chronic ---infection ---insult ---SIRS > End-stage liver disease --- insufficient hepatocytes ---"run out of liver"
What happens in the liver sinusoids?
Arterial and venous blood mixes
Route blood takes through the liver?
Hepatic artery and hepatic portal vein –> arterioles and venues –> sinusoids –> central vein of liver lobule –> branches of hepatic vein –> hepatic vein
Features of liver lobules
- Hexagonal
- Has a branch of hepatic vein at its centre (central vein)
- Has a triad at each of its six corners with branches of hepatic portal vein, hepatic artery and bile duct
- Cords of hepatocytes arranged as hepatic plates
- BLOOD flows INWARDLY through sinusoids to the central vein
- Bile flows OUTWARDLY through canaliculli to the bile duct
How are HEPATOCYTES arranged?
Arranged in between sinusoids in plates two cells thick
- BASOLATERAL membrane faces the SPACE OF DISSE (extracellular gap between the latter and the endothelial cells that line the fenestrated sinusoids)
- APICAL membrane of adjacent hepatocytes is grooved and forms the canaliculli
What do SINUSOIDAL SPACES contain?
> Endothelial cells
- form a fenestrated structure, allowing for free movement of solutes
> Kuppfer cells
- macrophages resident to the sinusoidal space, remove particulate matter and senescent erythrocytes
> Stellate (Ito) cells
- within the space of Disse
- important for vitamin A storage
Intrahepatic Bile System
Canaliculi -> terminal bile ductules -> perilobular ducts -> interlobular ducts -> septal ducts -> lobar ducts -> two hepatic ducts -> the common hepatic duct
Bile production between meals
Stored and concentrated in the gall bladder (sphincter of Oddi closed)
Bile production DURING a meal
- Chyme in duodenum stimulates gall bladder smooth muscle to contract
- Sphincter of Oddi opens
- Bile spurts into duodenum via cystic and common bile ducts
- Digestion and absorption of fat
How does gall bladder contract, and the sphincter of oddi open?
CCK and vagal impulses
Bile from Bile Duct Cells
Alkaline, HCO3 rich
Between meals has an ionic composition
neutralisation of chyme
pH adjustment for enzyme action
mucosal protection
Bile from HEPATOCYTES
> secreted into canaliculli > Primary bile acids - CHOLIC and CHENODEOXYCHOLIC acids > Water and electrolytes > Lipids and phospholipids > Cholesterol > IgA > Bilirubin
What effect can excess cholesterol relative to bile acids have?
Excess cholesterol may precipitate into micro crystals which aggregate into GALL STONES
What can be used to get rid of gall stones?
URSODEOXYCHOLIC ACID may be used to dissolve non-calcined cholesterol gall stones
Bilirubin
Breakdown product of the porphyrin component of Hb
Pigment rendering urine yellow and faeces brown
Causes JAUNDICE in excess
Enterohepatic Recycling
Only a small fraction of bile salts entering the duodenum is lost in the faeces
MOST is REABSORBED by active transport in the terminal ileum and undergoes enterohepatic recycling
Which drugs make use of this system?
> RESINS > Colestyramine, colestipol > Bind bile salts > Prevent reabsorption > Lower plasma cholesterol
Drug metabolism aims
> Convert parent drugs to more polar metabolites that are NOT readily absorbed by the kidneys –> excretion
> Convert drugs to metabolites that are usually less active than parent compound
> BUT, can be converted from inactive PRODRUGS to active compounds
> have unchanged activity
> possess a different type or spectrum of action (aspirin –> salicylic acid)
Drug Metabolism Phases
> Phase 1
- makes drugs more polar, adds a chemically reactive group permitting conjugation
- Oxidation
- Reduction
- Hydrolysis
> Phase 2
- CONJUGATION
- Adds an endogenous compound increasing polarity
> Not all drugs go through both phases, or can completely circumvent it before being excreted
Cytochrome P450 (CYP) Monooxygenases
> Mediate OXIDATION reactions (phase 1)
Located in the endoplasmic reticulum
Have distinct, but overlapping substrate specificities
What are the main gene families of CYP in the liver?
CYP1, 2 & 3
Monooxygenase P450 Cycle
> Drug enters cycle as drug substrate
Molecular oxygen provides 2 atoms of oxygen
One atom of oxygen is added to the drug to give the HYDROXYL PRODUCT
This leaves the cycle
the second oxygen combines with protons to form H2O
Phase 2 Reactions
> Usually result in inactive products
Conjugation of chemically reactive groups
Glucuronidation is a common reaction
Transfer of glucoronic acid –> electron-rich atoms
Bilirubin & adrenal corticosteroids
Hepatic Encephalopathy & Therapy
> Detoxification of NH3 to Urea does NOT occur in severe hepatic failure, blood NH3 levels rise resulting in coma
> Therapy - Lactulose, antibiotics (neomycin, rifaximin)
What does electrophoresis allow?
Separation of proteins by size
Functions of plasma proteins
> maintenance of oncotic or colloid osmotic pressure (maintain BP) > transport of hydrophobic substances > pH buffering > Enzymatic > Immunity
alpha globulins
> transport lipoproteins, lipids, hormones and bilirubin
Cu2+
retinol binding protein (transports vitamin A)
Beta Globulins
> Transferrin (transports ferric ions in the body, Fe3+)
> Fibrinogen (inactive form of fibrin)
Albumin
> Most abundant plasma protein
- small, negatively charged, water-soluble
- main determinant of plasma oncotic pressure
> Liver synthesises about 14g/day
Which hormone stimulates albumin production?
Insulin
How is iron transported in the body?
> Transported as ferric ion, Fe3+
- bound to TRANSFERRIN in blood
How is iron STORED?
> In liver cells as Fe2+ bound to FERRITIN
How is COPPER transported in the blood?
> By Ceruloplasmin
deficiency of which causes Wilson’s disease
Steroid hormones and T3/T4 thyroid hormones are hydrophilic/hydrophobic?
HYDROPHOBIC
How is THYROXINE transported in the blood?
Bound to thyroid-binding globulin
How is CORTISOL transported in the blood?
Bound to cortisol-binding globulin
Lipoproteins
> core
> shell
> Core of cholesterol esters and tricgylcerides
Shell made up of polar lipids and phospholipids, APOPROTEINS
> Free cholesterol dispersed throughout
Fat transport between organs and tissues
Reverse cholesterol transport
> HDL
Removes excess cholesterol from cells
Liver is the only organ that can metabolise and excrete cholesterol
Cholesterol synthesis
Main site is the LIVER
Needs a lot of energy (36 ATP)
Using HMG-CoA reductase
HMG-Coa
> Catalyses the formation of MEVALONIC ACID
Rate limiting enzyme
Fasting stimulates activity and synthesis
Target for STATINS
Vitamin D
> Role in regulation of calcium and phosphorus metabolism
Most abundant form is vitamin D3
Derived from cholesterol
Where are corticosteroids synthesised?
Adrenal cortex
cholesterol derivative
Where are ANDROGENS synthesised?
Testis
cholesterol derivative
Where are ESTROGENS synthesised?
Ovary
cholesterol derivative
What is the main metabolic product of cholesterol?
BILE SALTS
Bile salt resins
Bind bile salts and inhibit reabsorption in the enterohepatic circulation
Increased bile salt excretion
Increased synthesis of bile salts
therefore, concentration of cholesterol in liver decreases
Number of LDL receptors of hepatic cells increases
Uptake of LDL cholesterol from plasma increases
–> lower plasma LDL
Wernicke-Korsakoff Syndrome
> Thiamine deficiency (vitamin b1)
Ataxia and confusion (Wernicke encephalopathy)
Memory impairment (Korsakoff syndrome)
Chronic Effects of ALCOHOL consumption
• G.I. o Stomach o Liver o Pancreas • C.V. o Hypertension o Cardiomyopathy o M.I. o Stroke • C.N.S. o Neuropathies o Cerebellar degeneration o Dementia o Wernicke-Korsakoff’s syndrome ♣ Thiamine deficiency • Hematologic o Anaemia o Bone marrow suppression • Musculoskeletal o Proximal myopathy • Endocrine • Dermatologic • Reproductive
Solid liver lesions in older patients are more likely to be?
Malignant, in absence of liver disease
Solid liver lesions in chronic liver disease patients more likely to be?
Primary liver cancer
What is the most common solid liver tumour in NON CIRRHOTIC patients
HAEMANGIOMAS
Focal liver lesions are normally found in what fashion?
Picked up incidentally on scans
Benign Liver Lesions
> Haemangioma
Focal Nodular Hyperplasia
Adenoma
Liver cysts
Malignant liver lesions
- Primary liver cancers
- Hepatocellular carcinoma
- Cholangiocarcinoma
- -> Fibrolamellar carcinoma
- -> hepatoblastoma - Metastases
Haemangioma
- Commonest liver tumour
- more females affected
- Hypervascular
- Single, small tumour
- Well defined
- Asymptomatic
Diagnosis
> US: echogenic spot
> CT: venous enhancement from periphery to centre
> MRI: High intensity area
Treatment
> no need for treatment
> not a premalignant pre cursor
Focal Nodular Hyperplasia (FNH)
- Features
- Diagnosis
- Treatment
> Benign nodule formation
Associated with Osler-Weber-Rendu and liver haemanagioma
Central scar containing a large artery, radiating branches to the periphery (HUB & SPOKE)
Hyperplastic response to abnormal arterial flow
More common in young/middle aged women
Asymptomatic, minimal pain
Diagnosis
> US: nodule with varying echogenicity
CT: hypervascular mass with central scar
MRI: Iso or hypo intense
FNA: normal hepatocytes and kupffer cells with central core
Treatment
> No treatment necessary
What does FNA stand for?
- Fine Needle Aspiration
- Used to get a sample and analyse cytology/histology
Hepatic Adenoma
Clinical Features
- Hormone related
- Benign neoplasm composed of normal hepatocytes (no portal tract, central veins or bile ducts)
- More common in women
- Contraceptive hormones and anabolic steroids
- Asymptomatic, may have RUQ pain
- Found in RIGHT LOBE
- May present with rupture, haemorrhage, or malignant transformation
- Malignant transformation risk higher in males
- Symptoms are size-related
- Regression of tumour can occur if oral contraceptive is discontinued
Diagnosis
US: Filling defect
CT: Diffuse arterial enhancement
MRI: Hypo or hyper intense lesion
FNA: May be needed
Treatment
> Stop hormones, weight loss
Males (irrespective of size) : surgical excision
Females : imaging after 6months
<5cm or reducing in size - annual MRI
>5cm or increase in size - for surgical excision
Simple liver CYST
> Liquid collection lined by an epithelium > no biliary tree communication > Solitary > Asymptomatic > Symptoms related to -intracystic haemorrhage - infection - rupture - compression
Management
> no follow up necessary
if doubt, imaging 3-6 months
consider surgical intervention (huge cyst)
Hydatid Cyst (caused by)
- Echinoccocus granulises
- due to ingestion of eggs of the tapeworm
- not so common here
- presentation of disseminated disease, erosion of cysts into adjacent structures
- detection of anti-echinococcus antibodies
Management
> SURGERY
- open cystectomy
- pericystectomy, lobectomy
Risks - operative morbidity, anaphylaxis, dissemination of infection
What medication would be used to treat parasites causing hydatid cysts?
Albendazole
Polycystic Liver Disease (PLD)
- Embryonic ductal plate malformation of the intrahepatic biliary tree
- Numerous cysts throughout liver parenchyma
What are the three types of PLD?
- Polycystic Liver Disease
- Von Meyenburg complexes
- Autosomal dominant poyscystic kidney disease
Von Meyenburg Complex (VMC)
Type of polycystic liver disease
- microhamartomas
- benign cystic nodules throughout the liver
- cystic bile duct malformations
- silent during life, usually
- incidental finding
Polycystic Liver Disease (PCLD)
- Liver function preserved, renal failure is rare
- symtpoms depend on the size of the cysts
- PCLD gene: PRKCSH and SEC63
Autosomal Dominant Polycystic Kidney Disease (ADPKD)
- Renal failure due to polycystic kidneys and non-real extra-hepatic features
- Potential massive hepatic enlargement
- ADPKD genes - PKD1 and PKD2
Polycystic Liver Disease - Management
C/O abdominal pain, abdominal distension, atypical symptoms due to voluminous cysts resulting in compression of adjacent tissue or failure of the affected organ
Conservative treatment is recommended to halt cyst growth to allow abdominal decompression and ameliorate symptoms
Invasive procedures are rarely required only in selective patient group with advanced PCLD, ADPKD or liver failure
- Defenestration/aspiration
- Liver transplantation
Pharmacological therapy by somatostatin analogues lead to beneficial outcome of PLD in terms of symptom relief and liver volume reduction
Liver Abscess
Clinical Features//
- High fever/septic
- Leukocytosis
- Abdo pain
- Complex liver lesion
History//
abdo or biliary infection
Dental procedure
Management//
> Initial empiric broad spectrum antibiotics
> Aspiration/drainage percutaneously
> Echocardiogram
> Operation if no clinical improvement:
- Open drainage
- Resection
> 4 weeks antibiotic therapy with repeat imaging
Hepatocellular Carcinoma (HCC)
- Risk factors
- Clinical Features
- Metastases
- Diagnosis
- Prognosis
Risk Factors//
Cirrhosis from any cause:
- Hep B
- Hep C
- Alcohol
- Alfatoxin
- Other
Clinical Features//
- weight loss and RUQ pain (commenest)
- Asymptomatic
- Worsening of pre-existing chronic liver disease
- Acute liver failure
o/e. Signs of cirrhosis; hard, enlarged RUQ mass.
Liver bruit
Metastases//
- rest of liver
- portal vein
- lymph ndoes
- lung
- bone
- brain
Diagnosis//
- clinical presentation
- elevated AFP
- Ultrasound
- Triphasic CT scan
- MRI
- Biopsy
Prognosis//
- Tumour size
- Extrahepatic spread –> worsens prognosis
- Underlying liver disease
- Patient performance status
- Poor life expectancy
What is Alfa fetoprotein?
> HCC tumour marker
values > 100ng/ml highly suggestive of HCC
Elevation seen in majority of patients
Larger the tumour –> more alfa fetoprotein
Small lesions may not cause a rise
What is the diagnostic method of choice in hepatocellular carcinoma?
Imaging
Hepatocellular Carcinoma - therapeutic options
> Liver transplant
- BEST treatment
- only if single tumour is less than 5cm in size or fewer than 3 tumours less than 3cm each
> Resection
- feasible for small tumours with preserved liver function
> Local ablation
- for non-resectable pt
- for pt with advanced liver cirrhosis
- alcohol injection
- radio frequency ablation
- temporary measure
> Chemoembolisation
- TACE
- – Trans Arterial Chemo Embolisation
- Inject chemo selectively in hepatic artery
- then inject an embolic agent
- for patients with early cirrhosis
> Systemic Therapies
- Sorafenib
- multikinase inhibitor of vascular endothelial gf receptor
Fibro-Lamellar Carcinoma
- Presents in young pt
- AFP norma
- Not related to cirrhosis
- Stellate scar on CT, radial septa
- SURGICAL RESECTION or TRANSPLANTATION
Secondary Liver Metastases
- Most common site for blood-born metastases
- Common primaries: colon, breast , lung, stomach, pancreas, melanoma
- Mild cholestatic picture (ALP) with preserved liver function
- Dx imaging or FNA
- Treatment depends on primary cancer
- Resection or chemoembolisation is sometimes possible
Conjugated Bilirubin
The bilirubin has been through the conjugation process within the liver by UDP glucuronosyltransferase
Water soluble
Therefore can be excreted by kidneys
Unconjugated bilirubin
Has not yet been through the liver
NOT water soluble
Excess unconjugated bilirubin –> Crigler-Najjar Syndrome
Crigler-Najjar Syndrome
- Autosomal recessive
- Jaundice in neonates and babies due to LACK/NONE of UDP– glucuronosyltransferase
- Build up of unconjugated bilirubin
What are the true LFTs?
Prothrombin Time (PT) & Albumin
What are the liver enzymes?
ALT AST, ALP, Bilirubin and GGT
Signs of COMPENSATED CIRRHOSIS
- Spider naevi
- Palmar erythema
- Clubbing
- Gynaecomastia
- Hepatomegaly
- Splenomegaly
- NONE
Signs of Decompensated Cirrhosis
- Jaundice
- Ascites
- Encephalopathy
- Bruising
Treatment of decompensated cirrhosis?
- Remove or treat the underlying cause
- Look for and treat infection
• NUTRITION
> energy intake of 35-40 kcal/kg)
> protein intake of 1.2-1.5g/kg
small frequent meals and snacks
• Vitamin and Mineral Requirements
> vitamin B supplementation
> Thiamine
> Calcium and vitamin D to counter osteoporosis
COMPLICATIONS of Cirrhosis
- Ascites
- Encephalopathy
- Variceal bleeding
- Liver failure
Ascites
> Accumulation of fluid in the peritoneal cavity
TREATMENT//
> Improve underlying liver disease
> Look for and treat infection
> NO NSAIDS
> Reduce salt intake , maintain nutrition
> Diuretics – SPIRONOLACTONE
> Paracentesis
- – rapid relief
- –risk of infection and encephalopathy
- – hypovolaemia
> TIPSS
- stent within the liver
> Transplantation
abstain from alcohol.
Diuretics for ascites
> new ascites
recurrent ascites
> Spironolactone, first line in new ascites
In recurrent use step-wise increments of spironolactone + LOOP diuretic
> Monitor U&Es
Spontaneous Bacterial Peritonitis (SBP)
> Translocated bacterial peritonitis
Diagnosis//
- tap of ascites and cell count
- neutrophil count >250cells/mm^3
Treatment//
- Urgent
- Abx
- Terlipressin
- Maintain renal perfusion
- HRS development (hepatorenal syndrome)
Encephalopathy
> Cause
Diagnosis
Treatment
- Microglial inflammation
- Build up of ammonia
Diagnosis//
- Liver flap
- Confusion
- any neurology
Treatment//
Look for cause and treat it
- infection
- metabolic
- drugs
- liver failure
> LACTULOSE
Maintain nutrition
> Consider TRANSPLANATION if spontaneous
Varices
> Increased portal pressure leading to formation of varices > 1/3 bleed > Decompensation > Liver failure > Death
Primary Prophylaxis//
- Beta blockers -> propranolol, carvideolol
- Variceal ligation
Secondary Prophylaxis//
- variceal banding
- beta blockers
Acute Variceal Bleeding//
- resus
- pharma therapy and timing
- failed therapy –> TIPSS, transection
Ballon tamponade
Sclerotherapy
Transplantation for liver disease
> UKELD score for transplantation
> Event based - ascites-resistant > Liver function based > Quality of life based - itch, lethargy, spontaneous encephalopathy
> UKELD score
- 1 year mortality, score = 49
Patients with a UKELD score of ≥49 to be listed for elective transplant
Unless they have:
- diuretic resistant ascites
- hepatopulmonary syndrome
- chronic hepatic encephalopathy
- intractable pruritus
- polycystic liver disease
- familial amyloidosis
> primary hyperlipidaemia
> HCC
Chronic Liver disease
- Duration
- Causes
> more than 6 months’ duration
progression –> cirrhosis
recurrent inflammation and repair with fibrosis and regeneration
Causes
- Alcohol
- NAFLD
- Hep C
- Primary biliary cirrhosis
- Autoimmune hepatitis
- Hepatitis B
- Haemochromatosis = build-up of iron in the body
- Primary Sclerosing Cholangitis
- Wilsons disease
o disorder of copper metabolism - Alpha-1 anti-trypsin deficiency
- Budd chiari
• occlusion of the hepatic veins
• Methotrexate
NAFLD
- Pathogenesis
- Associated with obesity
- FATTY LIVER/STEATOHEPATITIS (NASH) in absence of other cause
Pathogenesis//
> 2 hit hypothesis
1st hit
excess fat accumulation
2nd hit
- intrahepatic oxidative stress
- Lipid per oxidation
- TNF alpha, cytokine cascade
- Lipopolysaccharide
- Ischaemia-reperfusion injury
> ONE HIT
- triglyceride benign
- “Skinny” NASH
- Hepatocytes can generate TNFa
- OXIDATIVE STRESS
Diagnosis//
Elevated LFTs (around 100-150)
What is NASH
- Non Alcoholic Steatohepatitis
- most severe form of NAFLD
- maladaption to oxidative stress
Management
> Simple steatosis
NASH
Simple steatosis > diagnosis by USS > No liver outcomes > Increased CV risk > Treatment -- weight loss and exercise
NASH
> diagnosis by Liver biopsy
> risk of progression to cirrhosis
> WEIGHT LOSS AND EXERCISE
Primary Biliary Cirrhosis (Cholangitis) - PBC
> Mitochondrial Auto-antibodies (AMA antibodies)
More prevalent in older females
Symptoms
- fatigue (tired all day)
- itch without rash
- xanthelasma and xanthomas
- associated with high cholesterol
Diagnosis
> 2 of these 3
- +AMA
- Elevated ALP
- Liver biopsy
Treatment
- Urseodeoxycholic acid
- Control the itch
- tepid baths, transplant
Autoimmune Hepatitis Type 1
What type of necrosis?
- Adults
- Antinuclear antibodies (ANA)
- ASMA (anti-smooth muscle antibodies)
- SLA severity (soluble liver antigen)
Associated with extra-hepatic manifestations > thyroiditis > Graves disease > Chronic UC > SLE > Pernicious anaemia
Clinical Presentation
¥ Hepatomegaly ¥ Jaundice ¥ Stigmata of chronic liver disease ¥ Splenomegaly ¥ Elevated AST and ALT ¥ Elevated PT (prothrombin time) ¥ Non-specific symptoms: malaise, fatigue, lethargy, nausea, abdominal pain, anorexia
Diagnosis//
• Elevated AST and ALT
• Elevated IgG
* Presence of autoimmune antibodies
Histology//
> PIECEMEAL necrosis
Pathogenesis//
> Genetic predisposition + environemtanl agent
- HLA-DR3 (SEVERE)
- HLA-DR4 (late onset)
- Drugs
Treatment//
- corticosteroids
- azathioprine
- Prednisone + azathioprine
- Prednisone – start at 30mg daily and taper down to 15mg at week 4, then maintain on 10mg daily until therapy endpoint
- Azathioprine 50-100mg daily
Prognosis//
- many will develop cirrhosis
- oesophageal varices
- spontaneous resolution
Type 2 Autoimmnune Hepatitis
Children and young adults most affected
- LKM 1
- AMA
Primary SCLEROSING cholangitis
- Destructive disease of large and medium sized bile ducts
- more MALE
- recurrent CHOLANGITIS
Diagnosis//
- imaging of biliary tree, ERCP
Treatment//
- maintain bile flow
- monitor for cholangiocarcinoma & colorectal cancer
- Alcohol related
Haemochromatosis
- Genetic Iron Overload syndrome
- Cirrhosis, cardiomyopathy, pancreatic failure
- BRONZE diabetes
Treatment//
Venesection (removal of blood)
Alpha-1 Anti-Trypsin Deficiency (A1AT)
> Genetic mutations in A1AT genes - variable phenotype
> Protein function lost
–> excess tryptic activity
Clinical//
- Lung emphysema
- Liver deposition of mutant protein, cell damage
Treatment//
• supportive management
Methotrexate
> Drug used to treat rheumatoid arthritis and psoriasis
Dose dependent liver toxin –> progressive fibrosis
Clinical//
No signs
Monitor fibrosis
Treatment//
Discontinue the drug
Cardiac Cirrhosis
> Secondary to high right heart pressures
- incompetent tricuspid valve
- congenital
- rheumatic fever
- constrictive pericarditis
Clinical//
ascites and liver impairment
Treatment//
Treat the cardiac condition
Decompensated right ventricular or biventricular heart failure causes transmission of elevated right atrial pressure to the liver via the inferior vena cava and hepatic veins. At a cellular level, venous congestion impedes efficient drainage of sinusoidal blood flow into terminal hepatic venules. Sinusoidal stasis results in accumulation of deoxygenated blood, parenchymal atrophy, necrosis, collagen deposition, and, ultimately, fibrosis.
Hepatitis A
Transmission//
- faecal-oral spread
- poor hygiene/ overcrowding
- Gay men and PWID
Clinical//
- acute hepatitis
- – no chronic infection
- Older children/young adults
Labs//
- clotted blood for serology
- Hep A IgM
VACCINE
Hepatitis E
- More common in the tropics
- Faecal-oral transmission
- PREGNANT WOMEN
No vaccine
Some immunocompromised humans can become chronically infected
Hepatitis D
- Only found WITH hepatitis B virus
- Exacerbates Hep B infection
- SUPERINFECTION
Hepatitis B
all markers
Transmission//
> Sex (multiple sexual partners)
Mother to child
Blood (PWID)
Chronic infection
HBsAg+ //
> Hepatitis B surface antigen present in blood of all infectious individuals
> indicates patietn is infected and infectious, more than 6 months = chronic
HBeAg//
> Hep B e-antigen usually also present in highly infectious individuals
Hep B DNA tests also used
HepBIgM//
recently infected cases
Anti-HBe//
> indicates low infectivity
Anti-HBs//
Immunity
due to vaccine or due to past infection.
Control//
> minimise exposure
vaccination of at-risk people
Post-exposure prophylaxis
Spontaneous cure is sometimes seen in chronic infection
Hepatitis C
Transmission//
Similar to hep B - sex, blood, mother to child
less easily transmitted by sex than Hep B
Majority of cases - infection results in chronic infection
HepC antibody positive = past or active infection
HepC virus RNA//
positive = active infection negative = past infection
there is NO vaccine
Once chronic infection has been established, spontaneous cure is not seen.
High levels of chronic hepatitis C
–> Chronic hepatitis –> cirrhosis -> cancer and/or liver failure –> death
Time for a hepatitis infection to become cirrhosis?
> 20 years
Time for a hepatitis infection to become cancerous? (Hepatocellular carcinoma)
> 30 years
ACUTE viral hepatitis treatment
- No antivirals given
- Monitor for encephalopathy
- Monitor for resolution
- Notify public health
- immunisation of contacts
- test for other infections if at risk
- vaccinate against other infections if at risk
CHRONIC viral hepatitis management
ANTIVIRALS
- genotype of Hep C important in deciding regime
> Vaccination
Infection Control
Decreased alcohol intake
HCC screening
Acute Liver Disease
- Rapid development of hepatic dysfunction without prior liver disease
- any insult to the liver causing DAMAGE in a previously normal liver
- <6 months duration
–> Encephalopathy and prolonged coagulation
Clinical features of acute liver disease
- [none]
- jaundice
- lethargy
- nausea
- anorexia
- pain
- itch
- arthralgia
- ABNORMAL LFTs
Causes of Acute liver failure
• Viral A,B,C,D,E,CMV EBV &Toxoplasmosis • Drugs • Shock liver - massive hyper perfusion to the liver • Cholangitis • Alcohol • Malignancy • Chronic Liver Disease • Ask about paracetamol RARE •Budd Chiari •AFLP •Cholestatsis of Pregnancy
Acute liver failure Investigations
- HISTORY
o Symptoms
o Duration
o Drugs
♣ INCLUDING OTC
♣ Herbal (been known to cause liver damage)
♣ Food supplements
♣ Health food shop shite
o Possible toxins
o Alcohol history
- LFTs
- History and Examination
- Ultra-sound
- Virology
- Ix of chronic liver disease
- RARELY – biopsyAcute Liver Failure TREATMENT
- Rest
- Fluids
- Increase calories (35-40 kcal/kg/day & 1.2-1.5g protein/kg/day)
- monitor and supplement electrolytes: K, PO4 and Mg
- Hypoglycaemia
- For itch - sodium bicarb bath, urso acid
- Observation for FHF
Paracetamol and the liver
Paracetamol overdose
It is converted to NAPQI by p4502E1
NAPQI is toxic.
Normally it is then converted to a non-toxic form by GLUTATHIONE.
But due to excess paracetamol, there is a depletion of glutathione
Leaving the toxic NAPQI.
Liver damage
Drug-induced liver disease
> Antibiotics
- -co-amoxiclav
- flucloxacillin
> NSAIDs
> Fat burner or protein powders
> Nurofen and night nure (contain paracetamol)
Patients forget about some OTC medications that may potentially have paracetamol as an active ingredient.
Fulminant Hepatic Failure (FHF)
> Severe and sudden onset
severe impairment of hepatic functions or severe necrosis of hepatocytes
JAUNDICE & ENCEPHALOPATHY in a patient with a previously normal liver
Complications//
- hypoglycaemia
- coagulopathy
- circulatory failure
- renal failure
- infection
- Cerebral oedema and raised ICP
FHF causes
Common
>Paracetamol >Fulminant viral >Drugs >HBV >Non A-E
Rare
> AFLP (acute fatty liver of pregnancy) > Mushrooms > Malignancy > Wilsons > Budd Chiari > HAV
FHF Treatment
Supportive
> Inotropes and fluids
> renal replacement
> management of ICP
Transplantation
> life-long immunosuppression
FHF assessment
Refer quickly
repeat bloods and double check
short window of opportunity
will drop grade of encephalopathy on transfer
NO HESITATION if you think this is FHF
Grades of Encephalopathy
I Confusion
II Drowsiness. Liver flap
III Severe confusion and drowsiness. Liver flap
IV Coma
Antiviral Treatment - Who to treat
> Chronic Infection
Risk of complications
– evidence of inflammation/fibrosis sought
– increased ALTs
> Fit for treatment
- liver cancer is a contraindication
- established cirrhosis is more difficult to treat
- HIV co-infection more difficult to treat
> Patient Issues
- side effects of antivirals
- attitude to treatment
The higher a chronic HBV patient’s starting HBV-DNA load, the…?
Greater the risk of cancer on follow up
Interferon Alfa
Given as PEGINTERFERON - immune adjuvant
Side effects - flu like symptoms
Major - autoimmune disease, psychosis, thyroid disease
Hepatitis B therapy
Option 1//
> Peginterferon alone
Try in HBsAg and HBeAg pos patients with compensated disease
Option 2//
> suppressive antiviral drug > Advantage --safer -- increasing range available > Disadvantage --suppression not cure --resistance can develop
leading to reduction in HBV DNA (suppression)
Loss of HBeAg (enduring suppression)
Loss of HBsAg (CURE)
Improved liver function
Benefits of Chronic Hep C therapy
- Response defined by loss of HCV RNA in blood sustained to 6 months after ned of therapy
- Virological cure - SUSTAINED VIROLOGICAL RESPONSE (SVR)
- SVR patients have improved liver function
Types of Gallstones
> Cholesterol (pure yellow/ white)
> Pigment gallstones (black, excess bilirubin)
> Mixed (majority of gallstones)
> Primary bile duct stones (the stones themselves form within the bile ducts)
Gallstones - the 5 Fs
&
other risk factors
> Fair (more common white people)
> Fat (BMI > 30)
> Female
> Forty (age)
> Fertile (pregnancy, children)
High fat diet Hyperlipidaemia Bile salt loss (Crohn's) Dysmotility of GB Prolonged fasting Total parenteral nutrition
Biliary Colic
> Stone impacts in cystic duct
Gradual crescendo of pain in RUQ
Radiates to back/shoulder
May last hours
Not “colicky” - it does not come and go, despite what the name suggests.
Majority of patients experience this gradual increase in pain and it remains a severe and constant pain for hours afterwards.
Biliary colic - treatment
Pain killers, low fat diet
Lose weight
If recurrent episodes:
- surgery
- cholecystectomy
otherwise, if unfit
- Ursodeoxycholic acid (dissolves non-calcified gall stones)
Severe acute epigastric pain (differential)
> Bilariy colic > Peptic ulcer disease > Oesophageal spasm > Myocardial infarction > Acute pancreatitis
Acute cholecystitis
> Inflammation in gall bladder (obstruction of cystic duct)
> Gall bladder becomes swollen and inflamed
Acute cholecystitis - treatment
- IV abx and IV fluids
- Nil by mouth
Urgent cholecystectomy
What is the diagnostic tool of choice for acute cholecystitis?
> Ultrasound scan ***
- then
— CT, MRCP/ERCP, HIDA, EUS
Complications of gallstones
Stones may migrate in common bile duct.
- -> - Jaundice
- cholangitis
- acute pancreatitis (due to back pressure)
Gallstone ileum
MRCP (magnetic resonance cholangiopancreatography)
> Itch, nausea, anorexia
Jaundice
Abnormal LFTs
ERCP (can you remove stones?)
May be able to remove the stone there and then if it is small enough
Balloon ERCP
Dormia basket ERCP
Acute Pancreatitis
> ALCOHOL/ gallstones
Autodigestion of peri-pancreatic tissues by activated enzymes
Cholecystectomy during INDEX admission
ERCP
ES = Endoscopic Sphincterectomy
Gallstone Ileus
> Small bowel obstruction - gallstone impacted in distal ileum
> Fistula gallbladder + duodenum –> large gallstone passes into small intestine
> Moves down SB causing intermittent colic
> Present with distal SB obstruction
–>Ascites
dilatation
air in bile duct
Gallstone Ileus - treatment
> Urgent laparotomy - Small bowel enterotomy to remove stone
> Interval cholecystectomy in 3 months
- squeeze the stone out
Cholangiocarcinoma
> Usually late presentation
- jaundice
- weight loss
- anorexia
- lethargy
> Lymph node metastases
20-30% peritoneal metastases
Cholangiocarcinoma - diagnosis
> Duplex ultrasound
> Spiral CT/ ERCP/ PTC
> MRI
Types I - IV staging.
I - below confluence of hepatic ducts
II - confined to confluence
IIIa - extension into right hepatic duct
IIIb -extension into left hepatic duct
IV - extension into right and left hepatic duct
Cholangiocarcinoma - treatment
Curative & palliative
Surgical resection.
Bile duct and liver resection.
Palliative//
Biliary stent
