Gastroenterology Flashcards
what is the stepwise progression to becoming alcoholic liver disease?
alcohol related fatty liver - reversible
alcoholic hepatitis - reversible with permanent abstinence
cirrhosis - scar tissue, irreversible
what is the recommended alcohol consumption?
no more than 14 units of alcohol per week for both men and women over 3 ore more days and no more than 5 a day
how can harmful alcohol abuse be screened for?
C – CUT DOWN? Ever thought you should?
A – ANNOYED? Do you get annoyed at others commenting on your drinking?
G – GUILTY? Ever feel guilty about drinking?
E – EYE OPENER? Ever drink in the morning to help your hangover/nerves?
how are people screened for harmful alcohol use?
Alcohol Use Disorders Identification Test (AUDIT) questionnaire
what are the complications of alcohol?
Alcoholic Liver Disease
Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma
Alcohol Dependence and Withdrawal
Wernicke-Korsakoff Syndrome (WKS)
Pancreatitis
Alcoholic Cardiomyopathy
what are the signs of liver disease?
Jaundice
Hepatomegaly
Spider Naevi
Palmar Erythema
Gynaecomastia
Bruising – due to abnormal clotting
Ascites
Caput Medusae – engorged superficial epigastric veins
Asterixis – “flapping tremor” in decompensated liver disease
which investigations are required for suspected liver disease?
FBC – raised MCV
LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis.
Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver
U+Es may be deranged in hepatorenal syndrome.
which scans could be used to establish liver disease and the results?
USS - fatty changes, fibrosis
endoscopy - assess and treat varices from portal hypertension
CT/MRI- fatty change, carcinoma, megaly, abnormal blood vessel changes and ascites
biopsy
what is the general management of alcoholic liver disease?
Stop drinking alcohol
Consider a detoxication regime
Nutritional support with vitamins (particularly thiamine) and a high protein diet
Steroids improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term
Treat complications of cirrhosis (portal hypertension, varices, ascites and hepatic encephalopathy)
Referral for liver transplant in severe disease however they must abstain from alcohol for 3 months prior to referral
what are the complications of alcohol withdrawal and when do they occur?
6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: “delirium tremens”
define delirium tremens
medical emergency
alcohol stimulates GABAr - relaxing
and inhibits glutamate r - also inhibitory
but chronic use - GABA downregulated and glutamate upregulated…excitability and adrenergic activity
what does delirium tremens present with?
Acute confusion
Severe agitation
Delusions and hallucinations
Tremor
Tachycardia
Hypertension
Hyperthermia
Ataxia (difficulties with coordinated movements)
Arrhythmias
how can alcohol withdrawal be assessed?
CIWA-Ar (Clinical Institute Withdrawal Assessment – Alcohol revised)
what drugs is used to control alcohol withdrawal?
chlordiazepoxide - benzodiazepine
Iv high dose B vitamins and oral thiamine
define wernicke-korsakoff syndrome
Alcohol excess leads to thiamine (vitamin B1) deficiency. . Wernicke’s encephalopathy comes before Korsakoffs syndrome
what are the clinical fx of Wernicke’s encephalopathy?
Confusion
Oculomotor disturbances (disturbances of eye movements)
Ataxia (difficulties with coordinated movements)
what are the clinical fx of korsakoffs syndrome?
Memory impairment (retrograde and anterograde)
Behavioural changes
how is WKS treated/
stop alcohol
thiamine supplements
wwhat are the most common causes of cirrhosis?
Alcoholic liver disease
Non Alcoholic Fatty Liver Disease
Hepatitis B
Hepatitis C
what are the rarer causes of cirrhosis?
Autoimmune hepatitis
Primary biliary cirrhosis
Haemochromatosis
Wilsons Disease
Alpha-1 antitrypsin deficiency
Cystic fibrosis
Drugs (e.g. amiodarone, methotrexate, sodium valproate)
what are the signs of cirrhosis?
Jaundice – caused by raised bilirubin
Hepatomegaly – however the liver can shrink as it becomes more cirrhotic
Splenomegaly – due to portal hypertension
Spider Naevi – these are telangiectasia with a central arteriole and small vessels radiating away
Palmar Erythema – caused by hyperdynamic cirulation
Gynaecomastia and testicular atrophy in males due to endocrine dysfunction
Bruising – due to abnormal clotting
Ascites
Caput Medusae – distended paraumbilical veins due to portal hypertension
Asterixis – “flapping tremor” in decompensated liver disease
which investigations are required for cirrhosis?
Liver biochemistry is often normal, however in decompensated cirrhosis all of the markers (ALT, AST, ALP and bilirubin) become deranged.
The albumin level drops and the prothrombin time increases as the synthetic function becomes worse.
Hyponatraemia indicates fluid retention in severe liver disease.
Urea and creatinine become deranged in hepatorenal syndrome.
Further bloods can help establish the cause of the cirrhosis if unknown (such as viral markers and autoantibodies).
Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma and can be checked every 6 months as a screening test in patients with cirrhosis along with ultrasound.
enhanced liver fibrosis - >7.7, not always possible
what may imaging show of cirrhosis?
USS- nodularity, corkscrew appearance of arteries, enlarged portal vein, ascites, splenomegaly
fibro scan - every 2 yrs if at risk, elasticity, degree of cirrhosis
endoscopy -varices
CT/MRI
biopsy
how is heptatocellular carcinoma screened for?
USS, every 6 mths
how is the severity of cirrhosis scored?
child-pugh score
- billirubin
- albumin
- INR
- ascites
- encephalopathy
if compensated - MELD score
what does the general management of cirrhosis involve?
Ultrasound and alpha-fetoprotein every 6 months for hepatocellular carcinoma
Endoscopy every 3 years in patients without known varices
High protein, low sodium diet
MELD score every 6 months
Consideration of a liver transplant
Managing complications as below
what are the complications of cirrhosis?
Malnutrition
Portal Hypertension, Varices and Variceal Bleeding
Ascites and Spontaneous Bacterial Peritonitis (SBP)
Hepato-renal Syndrome
Hepatic Encephalopathy
Hepatocellular Carcinoma
how does cirrhosis lead to malnutrition and how is this managed?
increased use of muscle tissue as fuel and reduces protein available in body for muscle growth
also disrupts livers ability to store glucose as glycogen when required…muscle wasting and weight loss
- regular meals
- low sodium
- high protein and calorie
- avoid alcohol
how does liver cirrhosis lead to portal hypertension?
increases resistance of blood flow…back flow in portal system..vessels at the sites where portal system to anastome with systemic venous system to become sweollen and tortuouse…varices
at gastro-oesophageal, ileocaecal, rectal, ant abdo walla via umbilical vein (Caput medusae)
once start bleeding wont stop, but asx
how are stable varices managed?
Propranolol reduces portal hypertension by acting as a non-selective beta blocker
Elastic band ligation of varices
Injection of sclerosant (less effective than band ligation)
Transjugular Intra-hepatic Portosystemic Shunt (TIPS) is a technique where an interventional radiologist inserts a wire under xray guidance into the jugular vein, down the vena cava and into the liver via the hepatic vein. They then make a connection through the liver tissue between the hepatic vein and the portal vein and put a stent in place. This allows blood to flow directly from the portal vein to the hepatic vein and relieves the pressure in the portal system and varices.
how are bleeding oesophageal varices managed?
resus - vasopressin analogues - vasoconstriction, correct coagulopathy with vit K and FFP, prophylactic abx, intubation and ICU
urgent endoscopy - inject sclerosant, elastic band ligation
sengstaken-blakemore tube into oesophagus if endoscopy fails
how do ascites form from cirrhosis?
increased pressure in portal system causes fluid to leak out of capillaries in the liver and bowel into peritoneal cavity…hypovolaemic so reduced blood flow to kindyes….so releases renin -> RAAS causing fluid and sodium reabsorption
it is a transudate - low protein content
how are ascites managed?
Low sodium diet
Anti-aldosterone diuretics (spironolactone)
Paracentesis (ascitic tap or ascitic drain)
Prophylactic antibiotics against spontaneous bacterial peritonitis (ciprofloxacin or norfloxacin) in patients with less than 15g/litre of protein in the ascitic fluid
Consider TIPS procedure in refractory ascites
Consider transplantation in refractory ascites
how does spontaneous bacterial peritonitis present?
Can be asymptomatic so have a low threshold for ascitic fluid culture
Fever
Abdominal pain
Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
Ileus
Hypotension
what are the most common organisms causing spontaneous bacterial peritonitis?
Escherichia coli
Klebsiella pnuemoniae
Gram positive cocci (such as staphylococcus and enterococcus)
how is spontaneous bacterial peritonitis managed?
ascitic culture
IV cephalosporin
define hepatorenal syndrome
Hypertension in the portal system leads to dilation of the portal blood vessels, stretched by large amounts of blood pooling there. This leads to a loss of blood volume in other areas of the circulation, including the kidneys. This leads hypotension in the kidney and activation of the renin-angiotensin system. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney. This leads to rapid deteriorating kidney function. Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed.
define hepatic encephalopatjy
causes by build up of toxins in brain..ammonia - functional impairment of liver in cirrhosis to metabolise, and collateral vessels develop to bypass liver cause ammonia to enter blood system directly
what are the precipitating factors of hepatic encephalopathy?
Constipation
Electrolyte disturbance
Infection
GI bleed
High protein diet
Medications (particularly sedative medications)
how is hepatic encephalopathy managed?
laxatives - promote excretion of ammonia
abx - rifaximin - less bacteria producing ammonia
nutrition - NG feeding
define non alcoholic fatty liver disease
forms part of the “metabolic syndrome” group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes - fatty deposits in liver cells intefering with function, can progress to hepatitis and cirrhosis
what are the risk factors for NAFLD?
Obesity
Poor diet and low activity levels
Type 2 diabetes
High cholesterol
Middle age onwards
Smoking
High blood pressure
what is a non invasive liver screen?
abnormal LFT’S-? next action
Ultrasound Liver
Hepatitis B and C serology
Autoantibodies (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis)
Immunoglobulins (autoimmune hepatitis and primary biliary cirrhosis)
Caeruloplasmin (Wilsons disease)
Alpha 1 Anti-trypsin levels (alpha 1 anti-trypsin deficiency)
Ferritin and Transferrin Saturation (hereditary haemochromatosis)
which autoantibodies attack the liver?
Antinuclear antibodies (ANA)
Smooth muscle antibodies (SMA)
Antimitochondrial antibodies (AMA)
Antibodies to liver kidney microsome type-1 (LKM-1)
how is non alcoholic fatty liver disease diagnosed?
liver USS - hepatic steatosis
ELF blood test - fibrosis (first line)
NAFLD fibrosis score
fibroscan
how is alcoholic fatty liver disease managed?
Weight loss
Exercise
Stop smoking
Control of diabetes, blood pressure and cholesterol
Avoid alcohol
when would you refer a pt to a liver specialist?
when have significant fibrosis - so need to be treated with vit E or pioglitazone
what are the causes of hepatitis?
Alcoholic hepatitis
Non alcoholic fatty liver disease
Viral hepatitis
Autoimmune hepatitis
Drug induced hepatitis (e.g. paracetamol overdose)
how does hepatitis present?
Abdominal pain
Fatigue
Pruritis (itching)
Muscle and joint aches
Nausea and vomiting
Jaundice
Fever (viral hepatitis)
what are the biochemical results for hepatitis?
high AST/ALT, proportionally more than ALP
billirubin rise
how common is hep A?
not in UK, most common worldwide
how is hep A transmitted and what sx does it cause?
faecal-oral route, usually by contaminated water or food
- N+V, anorexia, jaundice, cholestasis causing dark urine and pale stools, hepatomegaly
how is hep A managed?
analgesia- resolves in 1-3 months
vaccinated
notifiable disease to public health
how does hep B spread?
direct contact with blood or bodily fluids - sex, sharing needles, contaminated products such as toothrushes or minor cuts
mother to child
what is the prognosis of hep B?
most people recover within 2 months
10% develop chronic hep B carriers
what do the viral markers tell you about the presence of disease?
Surface antigen (HBsAg) – active infection
E antigen (HBeAg) – marker of viral replication and implies high infectivity
Core antibodies (HBcAb) – implies past or current infection
Surface antibody (HBsAb) – implies vaccination or past or current infection
Hepatitis B virus DNA (HBV DNA) – this is a direct count of the viral load
what does core antibodies tell you about the hepatitis sttatus?
IgM and IgG versions of the HBcAb. IgM implies an active infection and will give a high titre with an acute infection and a low titre with a chronic infection. IgG indicates a past infection where the HBsAg is negative.
what does hep B e antigen tell about the hepatitis status?
Hepatitis B e antigen (HBeAg) is important. Where the HBeAg is present it implies the patient is in an acute phase of the infection where the virus is actively replicating. The level of HBeAg correlates with their infectivity. If the HBeAg is higher, they are highly infectious to others. When they HBeAg is negative but the hepatitis B e antibody is positive this implies they have been through a phase where the virus was replicating and but the virus has now stopped replicating and they are less infectious
how are people vaccinated against hep B?
with hep B surface antigen
how do you manage hepatitis B?
Have a low threshold for screening patients that are at risk of hepatitis B.
Screen for other blood born viruses (hepatitis A and B and HIV) and other sexually transmitted diseases
Refer to gastroenterology, hepatology or infectious diseases for specialist management
Notify Public Health (it is a notifiable disease)
Stop smoking and alcohol
Education about reducing transmission and informing potential at risk contacts
Testing for complications: FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma
Antiviral medication can be used to slow the progression of the disease and reduce infectivity
Liver transplantation for end-stage liver diseas
how does hep C spread?
blood and bodily fluids
how is hep C managed?
NO VACCINE
curable with direct acting antiviral meds - need genotype
screen
notify public health
refer for specialist management
stop smoking and drinking
educate
test for complications - fibroscan for cirrhosis and USS for hepatocellular carcinoma
liver transplant for end stage liver disease
what is the prognosis of hep C?
1 in 4 rceovery
3 in 4 becomes chronic
what are the complications of hep C?
liver cirrhosis
heptacocellular carcinoma
how is hep C tested for?
hep C antibody
calculate viral load and assess for individual genotype
how does a hep D spread?
only survives in patients who already have a hep V infection..attaching to HBsAg
how serious is hep D and how is it treated?
Hep D increases complications and disease severity of hep B
notifiable disease
how is hep E transmitted?
faecal-oral route
how is hep E treated?
cleared within a month and no tx is usually required
rarely can progress to chronic hep and liver failure
NO VACCINATION
notified
what is the cause of autoimmune hepatitis?
unknown
genetic and environmental causing T cell mediated response against liver cells
what are the two types of autoimmune hepatitis?
type 1 - middle aged wmen, around or after menopause with fatigue and fx of liver disease
type 2 - teenage/early twenties present with acute hepatitis, high transaminases and jaundice
what biochemical results are there for autoimmune hepatitis?
raised ALT, AST
raised IgG
autoantibodies, type 1 - ANA, anti-actin, anti SLA/LP
type 2 - anti-LKM1, anti-LC1
confirmed with biopsy
how is autoimmune hepatitis treated?
high dose prednisolone
azathioprine
liver transplant
define haemochromatosis
iron storage disorder that results in excessive total body iron and deposition of iron in tissues
what is the genetic mutation involved in haemachromatosis?
HFE gene located on chromosome 6
autosomal recessive
what are the sx of haemochromatosis?
Chronic tiredness
Joint pain
Pigmentation (bronze / slate-grey discolouration)
Hair loss
Erectile dysfunction
Amenorrhoea
Cognitive symptoms (memory and mood disturbance)
presenting at age of 40 or later in females as menstruation eliminates iron from body
how is haemochromatosis diagnosed?
serum ferritin level (can rise in inflammation) so transferrin saturation is helpful in distinguishing between a high ferritin caused by iron overload (in which case transferrin saturation is high) from a high ferritin due to other causes such as inflammation or non alcoholic fatty liver disease…if both high, perform genetic test to confirm
liver biopsy with Perl’s stain - iron conc in parenchymal cells
CT abdo - attenuation
MRI - liver depositis of iron
what are the complications of haemochromatosis?
Type 1 Diabetes (iron affects the functioning of the pancreas)
Liver Cirrhosis
Iron deposits in the pituitary and gonads lead to endocrine and sexual problems (hypogonadism, impotence, amenorrhea, infertility)
Cardiomyopathy (iron deposits in the heart)
Hepatocellular Carcinoma
Hypothyroidism (iron deposits in the thyroid)
Chrondocalcinosis / pseudogout (calcium deposits in joints) causing arthritis
how is haemtochromatosis managed?
Venesection (a weekly protocol of removing blood to decrease total iron)
Monitoring serum ferritin
Avoid alcohol
Genetic counselling
Monitoring and treatment of complications
define wilson disease
excessive accumulation of copper in the body and tissue
what is the genetic mutation causing wilson’s disease?
mutation in the “Wilson disease protein” on chromosome 13. The Wilson disease protein also has the catchy name “ATP7B copper-binding protein”
autosomal recessive
what are the features of wilson’s disease?
Hepatic problems (40%)-
chronic hepatitis and cirrhosis,
Neurological problems (50%)
concentration and coordination difficulties, dysarthria, dystonia, parkinsonism, motor sx are assymetrical
Psychiatric problems (10%) -
mild depression, full psychosis
kayser-fleischer rings in cornea - brownish cirlces in iris
haemolytic anaemia
renal tubular acidosis
osteopenia
how is wilson’s disease diagnosed?
serum caeruloplasmin - low (can be falsely normal or elevated in cancer/inflammation)
liver biopsy - liver copper content (gold standard)
24 hour urine copper assay elevated
low serum copper
kayser-fleischer rings
MRI brain - non specific changes
how is wilson’s disease treated?
copper chelation -
Penicillamine
Trientene
what is the cause of alpha 1 antitrypsin defiency?
Alpha-1-antitrypsin (A1AT) is mainly produced in the liver, travels around the body and offers protection by inhibiting the neutrophil elastase enzyme. A1AT is coded for on chromosome 14. In A1AT deficiency, there is an autosomal recessive defect in the gene for A1AT
what are the two main organs affected by alpha 1 antitrypsin defiency?
liver - cirrhosis
lungs - bronchiecatsis and emphysema
how is cirrhosis caused by alpha 1 antitrypsin defiency?
normally alpha 1 antitrypsin created in liver - instead mutant version is produced, which gets trapped in liver, building up and causes damage…cirrhosis and then carcinoma
how are the lungs damaged by alpha 1 antitrypsin defieincy?
lack of normal alpha 1 leads to excess of protease which attacks C.T of lungs
