GI + Liver Flashcards
Role of liver
Glucose and fat metabolism
Protein synthesis e.g. albumin, clotting factors
Detoxification and excretion
Defence against infection: bilirubin, ammonia, drugs and hormone
reticuloendothelial system
Portal triad
Portal vein, hepatic A, bile duct
Acute liver injury results
Liver failure, recovery
Chronic liver injury results
Cirrhosis- scaring, can lead to liver failure
recovery
Liver failure (varices, hepatoma)
Causes of liver cell death
necrosis (associated with neutrophils), or apoptosis
Cirrhosis
Scarring of the liver, disturbs the portal triad
Causes of acute liver injury
viral (A,B, EBV)
drug
alcohol
Vascular
Obstruction
Congestion
Causes of chronic liver injury
alcohol
viral (B,C)
autoimmune
metabolic (iron, copper)
Presentation of acute liver injury
malaise, nausea, anorexia, jaundice
rarer (more common in failure): confusion, bleeding, liver pain, hypoglycaemia
Presentation of chronic liver injury
ascites, oedema, haematemesis (varices), malaise, anorexia, wasting easy bruising (clotting factors affected), itching, hepatomegaly, abnormal LFTs
rarer: jaundice (more related to acute), confusion
Chronic liver injury- management
Lifestyle changes and supportive treatment
Consider liver transplant
Acute liver injury- management
Identify and treat underlying cause
Monitor neurological status, blood tests
Consider liver transplant
Serum ‘liver function tests’
No one global test
Serum bilirubin, albumin, prothrombin time: (give some index of liver function)
Serum liver enzymes: -cholestatic: alkaline phosphatase, gamma-GT
-hepatocellular: transaminases (AST, ALT)- don’t give index of liver function
Jaundice
raised serum bilirubin
Pre-hepatic jaundice
Unconjugated bilirubin problems
Gilberts, Haemolysis
Hepatic jaundice
(conjugated bili) problems
Hepatitis: viral, drugs immune, alcohol
Ischaemia
Neoplasm
Congestion (CCF)
Post-hepatic jaundice
(conjugated) problems
Gallstone: bile duct, Mirizzi
Stricture: malignant, ischaemic, inflammatory
Prehepatic jaundice tests
Urine- normal
Stool- normal
Itching- no
Liver test- normal
Cholestatic jaundice tests
Urine- dark
Stool- may be pale
Itching- maybe
Liver test- abnormal
Jaundice history taking
Past history: biliary disease/intervention malignancy, heart failure blood products , autoimmune disease
Drug history (drugs/herbs started recently)
Social history- Alcohol, potential hepatitis contact (irregular sex, IVDU, exotic travel, certain foods)
Family Hx/ system review – rarely helpful
Jaundice investigations
Liver enzymes: Very high AST/ALT suggests liver disease, some exceptions
Biliary obstruction: 90% have dilated intrahepatic bile ducts on ultrasound
-no dilation means likely hepatic causes
Need further imaging: CT Magnetic resonance cholangioram MRCP Endoscopic retrograde cholangiogram ERCP
Gallstone
Most form in gallbladder- smaller stone more of a risk, than large stone that remain gallbladder
Very common: 1/3 women over 60
70% Cholesterol, 30% pigment+/- calcium
Gallstone risk factors
Risk factors: Female, fat, fertile (liver disease, ileal disease, TPN, clofibrate…)
Gallstone symptoms
Most asymptomatic
Weight loss, jaundice, referred in right shoulder
Gallstones presentation- in gallbladder
Biliary pain- yes
Cholecystitis- yes
Obstructive Jaunice- maybe (mirizzi)
Cholangitis- no
Pancreatitis- no
Gallstones presentation- in bile duct
Biliary pain- yes
Cholecystitis- no
Obstructive Jaunice- no
Cholangitis- yes
Pancreatitis- yes
Gallstones: management- gallbladder
Laparoscopic cholecystectomy
Bile acid dissolution therapy (<1/3 success)
Gallstones: management- bile duct stones
ERCP with sphincterotomy and:
removal (basket or balloon)
crushing (mechanical, laser..)
stent placement Surgery (large stones)
Are the ducts always dilated on ultrasound as result of gallstones
Ducts not always dilated on ultrasound (esp with “stone” jaundice)
Isoniazid complications
Acute liver injury
DRUG-INDUCED LIVER INJURY (DILI)
1/10000 patients/yr
30% of Acute Hepatitis
>65% of Acute Liver Failure - 50% Paracetamol
- 15% idiosyncratic- not due to ODs
Commonest reason for drug withdrawal from formulary
Types of DILI
Hepatocellular- ALT >2 ULN, ALT/Alk Phos ≥ 5
Cholestatic- Alk Phos >2 ULN or ratio ≤ 2
Mixed- Ratio > 2 but < 5
direct toxicity and idiosyncratic DILI
DILI: DIAGNOSTIC APPROACH
what did you start recently- usually 1-12 weeks of starting, onset may be weeks after stopping
resolution: 90% within 3 months of stopping
5-10%: prolonged- high mortality rate
DILI: “Usual Suspects”
32-45% Antibiotics
15% CNS Drugs-
5% Immunosuppressants
5-17% Analgesics/ musculoskeletal (Diclofenac…)
10% Gastrointestinal Drugs (PPIs…)
10% Dietary Supplements
20% Multiple drugs
Examples of drugs that commonly cause DILI- Antibiotics
Augmentin, Flucloxacillin, Erythromycin, Septrin, TB drugs
Examples of drugs that commonly cause DILI- CNS
Chlorpromazine, Carbamazepine Valproate, Paroxetin
Drugs unlikely to cause DILI
Low dose Aspirin
NSAIDs other than Diclofenac
Beta Blockers
HRT
ACE Inhibitors
Thiazides
Calcium channel blockers
Paracetamol metabolism
Acetaminophen> Stable
Metabolite > Excretion
Paracetamol OD
High doses of paracetamol produces liver cell necrosis. The toxic metabolite binds irreversibly to to liver cell membranes
Management of paracetamol induced fulminant hepatic failure
N acetyl Cysteine (NAC)
Supportive to correct
-coagulation defects, fluid electrolyte and acid base balance, renal failure, hypoglycaemia, encephalopathy
Paracetamol-induced liver failure: severity indicators
Late presentation (NAC less effective >24 hr)
Acidosis (pH <7.3)
Prothrommbin time > 70 sec
Serum creatinine ≥ 300 µmol/l
Consider emergency liver transplant- otherwise 80% mortality
Ascites- causes
Chronic liver disease (most) +/- Portal vein thrombosis, Hepatoma, TB
Neoplasia (ovary, uterus, pancreas…)
Pancreatitis, cardiac causes
Spider naevus
Vascular lesion characterized by anomalous dilatation of end vasculature found just beneath the skin surface- can be sign of cirrhosis, rheumatoid arthritis or hepatitis
Ascites- pathogenesis
Increased intrahepatic resistance + systemic vasodilation > secretion of Renin-angiotensin, Noradrenaline, Vasopressin + portal hypertension + low serum albumin
> fluid retention+ portal hypertension > ascites
Ascites- management
Fluid and salt restriction
Diuretics Spironolactone +/ Furosemide
Large-volume paracentesis + albumin
Trans-jugular intrahepatic portosystemic shunt (TIPS)
Alcohol liver disease and fat
Alcohol changes the way that hepatocytes metabolise and produce fat. Fat accumulation within hepatocytes is termed steatosis. It may be associated with acute liver injury, or as in the picture, chronic injury mediated by lymphocytes
Acute alcohol-related injury
causes hepatocyte ballooning and is mediated by neutrophils (acute alcoholic hepatitis)
Acute Decompensation
Fatty liver> alcohol hepatitis (90% of 1st episodes) or cirrhosis (more common later) +/ infection > acute decompensation
Alcoholic Liver Disease (ALD)
Main cause of liver death in UK
However, only 10-20% of heavy alcohol drinkers drinkers get serious ALD (unsure why)
Often not alcohol dependent
Poor outcome- 10 years survival 25%
Progression of Alcoholic Liver Disease (ALD)
Normal> Steatosis> Alcohol steatohepatitis/ fibrosis > Cirrhosis (or alcoholic hepatitis which can develop into cirrhosis) > Hepatocellular carcinoma
ALD management
Depends on type of liver disease
General- Stop drinking, Withdrawal symptoms treated with diazepam
Portal hypertension causes
cirrhosis, fibrosis, portal vein thrombosis
Portal hypertension- pathology
increased hepatic resistance, increased splanchnic blood flow
Portal hypertension complications
varices (oesophageal, gastric), splenomegaly
Liver transplantation for alcoholic liver disease?
Limited supply of liver, poor negative attitudes
However, post transplant survival similar to that for other liver diseases- did well
Drinking relapse –variable; recurrent ALD uncommon
Alcohol withdrawal treatment
Lorazepam
Causes of deterioration in chronic liver disease
Constipation
Drugs -sedatives, analgesics
NSAIDs, diuretics, ACE blockers
Gastrointestinal bleed
Infection (ascites, blood, skin, chest)
HYPO: natremia, kalaemia, glycaemia
Alcohol withdrawal (not typically)
Other (cardiac, intracranial)
Spontaneous bacterial peritonitis
Commonest serious infection in cirrhosis
based on neutrophils in ascitic fluid
Gram stain often neg; use blood culture bottles
After 1 episode:
-should have antibiotic prophylaxis
-consider liver transplantation
Renal failure in liver disease- causes
Drugs (diuretics, NSAIDS, ACEi, Aminoglycosides), Infection, GI bleeding, myoglobinuria, renal tract obstruction
Coma in patients with chronic liver disease
Hepatic encephalopathy (ammonia …) infection, GI bleed, constipation, hypokalaemia, drug (sedatives, analgesics)
Hyponatraemia / hypoglycaemia
Intracranial event
Encephalopathy
disease in which the functioning of the brain is affected by some agent or condition
Bedside tests for encephalopathy
Serial 7’s
WORLD backwards
Animal counting in 1 minute
Draw 5 point star
Number connection test
Other consequences of liver dysfunction
Malnutrition, coagulopathy, endocrine changes, hypoglycaemia
Drug prescribing in liver disease- Analgesia
sensitive to opiates
NSAIDs cause renal failure
paracetamol safest
Drug prescribing in liver disease- Sedation
use short-acting benzodiazepines- with care!!
Drug prescribing in liver disease- diuretics
excess weight loss hyponatraemia
hyperkalaemia
renal failure
Drug prescribing in liver disease- Antihypertensives
Can often stop, avoid ACEi
Drug prescribing in liver disease-
Aminoglycosides
Avoid!!!
Consequences of liver disease
Malnutrition
Variceal bleeding
Encephalopathy
Ascites / oedema
Infections- antibiotics
Treatment of consequences of liver disease- Malnutrition
Naso-gastric feeding
Treatment of consequences of liver disease- Variceal bleeding
Endoscopic banding, propranolol, terlipressin
Treatment of consequences of liver disease- Encephalopathy
lactulos
Treatment of consequences of liver disease- Ascites / oedema
salt / fluid restriction
diuretics, paracentesis
Liver patient ‘gone off’- what to do
ABC, look at chart (vital signs, O2, BM(glucose), drug chart), look at patient (focus of infection and bleeding)
Tests- FBC, U&E, blood cultures, ascitic fluid, clotting, LFTs
Causes of chronic liver disease
Alcohol
Non Alcoholic Steatohepatitis (NASH)
Viral hepatitis (B, C)
Immune cholangitis
Metabolic
Vascular - Budd-Chiari
Causes of chronic liver disease- immune
[autoimmune hepatitis, primary biliary cirrhosis, sclerosing
Causes of chronic liver disease- metabolic
haemochromatosis, Wilson’s, alpha-1 antitrypsin deficiency
Chronic liver- history taking
Past history: -alcohol problems, biliary surgery, autoimmune disease, blood products
Social history: alcohol, sexual
Drug history (all drugs!!)
Family history
Investigation of chronic liver disease
Viral serology
Immunology
Biochemistry
Radiological investigations
Investigation of chronic liver disease- Viral serology
Hepatitis B surface antigen, hepatitis C antibody
Investigation of chronic liver disease- Immunology
autoantibodies- AMA, ANA, ASMA,
coeliac antibodies
immunoglobulins
Investigation of chronic liver disease- biochem
iron/ copper studies
caeruloplasmin
24 hr urine copper
alpha1-antitrypsin level
lipids, glucose
Investigation of chronic liver disease- radiology
Ultrasound (USS) / CT / MRI
Normal flora
the community of microorganisms that live on another living organism without causing disease
Role of normal flora
produces antimicrobial substances which discourage infection by:
Inhibiting overgrowth of endogenous pathogens
Preventing colonisation by exogenous pathogens
Disruption to normal flora
Antibiotics can disrupt this balance increasing susceptibility to infections such as C.Difficile.
Peritonitis can occur as if normal barriers are breached
C.Difficile
Gram positive spore forming bacteria
Up to 5% of population have c.diff as normal flora
Many are asymptomatic but can become a problem if the normal gut flora is altered, most notably is due to broad spectrum antibiotics- rule of C’s
Rule of C’s
associated with a higher risk of C. difficile infection
clindamycin, ciprofloxacin (quinolones), co-amoxiclav (penicillins) and cephalosporins (particularly 2nd and 3rd generation)
C diff treatment
metronidazole or oral vancomycin.
In refractory cases sometimes faecal transplant- aims to restore the normal flora
Diarrhoea causes
Infective, inflammatory, loss of absorptive area, pancreatic disease, drugs, colon cancer, systemic disease, IBS, gastrectomy
Infective causes of diarrhoea
Campylobacter, salmonella, HIV, bacterial, amoebic dysentery, cholera
Diarrhoea- history
Onset/duration
Characteristics of stool
Food/drink
Travel
Immunocompromised
Unwell contacts
Hobbies + fresh water
Animal contact
Medications
Diarrhoea characteristics
floating: fat content ?malabsorption/ Coeliac
blood or mucus: ?inflammatory/ invasive infection ?cancer
Watery small bowel infection
Food and drink diarrhoea
Dodgy take-aways – food poisoning (eating food contaminated with microorganisms or toxins)
Meat/BBQs: campylobacter
Rice: bacillus cereus
Poultry: salmonella
Shellfish: norovirus, v.parahaemolyticus
Watery diarrhoea
non-inflammatory, proximal small bowel, bacterial, viral (rotavirus, norovirus) and parasitic causes
Water diarrhoea- bacterial causes
E coli
Clostridium perfringens – cooked meats
Bacillus cereus – reheated rice (vomiting +++)
Staph. aureus enterotoxin has a direct effect on vomiting centre in brain! <6hr exposure
Water diarrhoea- parasitic causes
Giardia – offensive diarrhoea, chronic, bloating, flatulence, nurseries/old age facilities
Cryptosporidium – swimming pools
Blood, mucoid diarrhoea
Inflammatory, colon, bacterial and parasitic causes
Blood, mucoid diarrhoea- bacterial causes
Shigella 🡪 shiga toxin, causes gross injury to bowel surface; MSM at risk
Salmonella – poultry, eggs and dairy
E coli
Vibrio parahaemolyticus – shellfish
C.Diff – antibiotics
Campylobacter – meats, BBQ
Blood, mucoid diarrhoea- parasitic causes
Entamoeba histolytica- travel, MSM
Most common GI infections in the UK
Mainly viral, ie rotavirus, norovirus
Diarrhoea definition
3 or more unformed stool per day plus one of the following:
Abdo pain
Cramps
Nausea
Vomiting
Dysenty
Traveller’s diarrhoea
occurs within 10 days of arrival from a foreign country, most commonly Enterotoxigenic E. coli, be aware of cholera
E.coli
Most strains are harmless
Some serotypes are pathogenic
Types of E coli
ETEC: EnteroToxigenic
EHEC: EnteroHaemorrhagic
EIEC: EnteroInvasive
EPEC: EnteroPathogenic
EAEC: EnteroAggregative
DAEC: Diffusely Adherent
E coli ETEC
leading bacterial cause of diarrhoea in children in developing world and most common cause of travellers diarrhoea
380000 deaths- mostly children in developing world
E colic EHEC
Shiga-like toxin – intensive inflammatory response
Can cause Haemolytic uraemic syndrome
Haemolytic uraemic syndrome
Bloody diarrhoea, abdo pain, no fever
Haemolysis
Renal failure
E. coli EIEC
Enteroinvasive, dysentery like illness, similar to shigella
Cholera
Contaminated food/water
Cholera toxin
Profuse watery “rice water” diarrhoea upto 20L a day
Vomiting
Rapid dehydration
Cholera treatment
Doxycycline and fluids
Immunosuppressed- more at risk to
Bacterial- Cryptosporidium, Mycobacteria, Microsporidia
Viral- CMV, HSV
Overall risk increased
Diarrhoea- lab tests
Stool tests- Microscopy, Culture
Ova, cysts and parasites, Toxin detection
Blood tests- Blood culture, Inflammatory markers (FBC/CRP)
Diarrhoea Red flags
Dehydration
Electrolyte imbalance
Renal failure
Immunocompromise
Severe abdominal pain
Cancer risk factors
Over 50, Chronic diarrhoea, Weight loss, Blood in stool, FH cancer, change in bowel symptoms
Diarrhoea- Key management principles
Fluids, electrolytes
Antiemetics if long time? (effective against vomiting and nausea)
Infection control
Do public health need to be connected, PPE when treating patient, deep cleaning
Are antibiotics a treatment for bacterial diarrhoea
No, unless they are immunocompromised
RUQ pain infections
Biliary sepsis aka ascending cholangitis
Liver abscess
Pneumonia
Lower abdominal pain infections
PID- pelvic inflammatory disease
Peptic Ulcer Disease
Helicobacter pylori- commonest cause of ulcer
Lives within mucus layer overlying the gastric mucosa
Peptic Ulcer Disease- treatment
CAP = Clarithromycin, Amoxicillin, PPI eg omeprazole
Acute Cholecystitis
Gallbladder inflammation, cystic duct obstruction by gall stones
RUQ or epigastric pain, fever and leucocytosis
Acute Cholecystitis- treatment
Diagnosis: By ultrasound
Treatment: IV fluids, analgesia and antibiotics
Surgery: Cholecystectomy
Ascending Cholangitis
Obstruction of the CBD
fever, abdominal pain, and jaundice (Charcot’s triad)
High mortality
Ascending Cholangitis- management
Prompt admission and IV antibiotics
ERCP- endoscopic retrograde cholangiopancreatography
Cholecystectomy
Liver abscess causes
Bacterial : faecal flora eg E.coli, Klebsiella spp etc
Amoebic: Entamoeba histolytica
Hydatid: Echinococcus granulosus (dog tapeworm)
Peritonitis causes
Medical – SBP (spontaneous bacterial peritonitis), PID (pelvic inflammatory disease), dialysis related, TB
Surgical – perforation of GIT
Enteric fever
aka typhoid
Mortality 20% 🡪 < 1% with antibiotics!
2-3% become carriers
Enteric fever symptoms
Generalised / R lower quadrant pain
High fever
“Relative bradycardia”
Headache and myalgia
Rose spots
Constipation/green diarrhoea
Enteric fever- management
Diagnosis- blood culture
Antibiotic, ?emergency surgery for complications
Enteric fever- complications
GI bleed
Perforation / peritonitis
Myocarditis
Abscesses
Hepatitis
Inflammation of the liver
Hepatitis differential diagnosis
viral (A, B, C, CMV, EBV)
drug-induced
autoimmune
alcoholic
Autoimmune hepatitis (AIH)
Progressive inflammatory liver condition, mostly effects females (75%), pathogenesis not fully understood
type 1- Anti nuclear (ANA), anti-smooth muscle, (ASMA)
Type 2- anti- liver/ kidney microsomal
Autoimmune hepatitis (AIH) clinical features
40% present with acute hepatitis
30% have cirrhosis at presentation
Patients may be asymptomatic or present with fatigue, and abnormalities in liver bichem or present with liver disease on examination
Autoimmune hepatitis (AIH) investigations
Liver biochem- ALT high, IgG raised
Liver biopsy- AIH requires liver biopsy for diagnosis and evaluate disease progression
Autoimmune hepatitis (AIH) treatment
prednisolone +/- azathioprine
Cirrhosis
Liver architecture is diffusely abnormal and interferes with liver blood flow and function, leads to portal hypertension and liver failure
Primary Biliary Cirrhosis (PBC)
Progressive disease- progressive destruction of interlobular bile ducts
Pathogenesis unknown
Mostly woman effected (90%)
Primary Biliary Cirrhosis/Cholangitis (PBC) clinical features
Mainly itching +/ fatigue, can be asymptomatic with lab abnormalities
other presentations include- dry eyes, joint pain, variceal bleeding and liver failure
Primary Biliary Cirrhosis/Cholangitis (PBC) investigations
Serum IgM- high
Liver biochem- often high serum alkaline is the only liver abnormality
Liver biopsy- required for diagnosis, characteristic portal tract infiltrate
Primary Biliary Cirrhosis/Cholangitis (PBC) management
Ursodeoxycholic acid- improves bilirubin and ALT levels, should be given in early phase, no benefit in advanced disease
Liver transplant
treatment of cholestatic itch- cholestyramine, Rifampicin, opioid antagonist
treatment of fatigue- disabling, trials for Modafinil (narcolepsy drug)
Ductopenia
destruction of the bile duct branch as a result of serve immune damage
Primary Sclerosing Cholangitis (PSC)
chronic cholestatic liver disease characterised by fibrosing inflammatory destruction of intra/ extrahepatic bile ducts
50% have IBS
10% develop into cholangiocarcinoma (bile duct cancer)
Primary Sclerosing Cholangitis (PSC) clinical features
With IBS- often asymptomatic and picked up by screening with high serum ALP
Symptoms include itching, pain ± rigors, jaundice
Primary Sclerosing Cholangitis (PSC) investigations
Magnetic Resonance Cholangiopancreatography (MRCP)- biliary changes- irregularity of calibre of both intra and extrahepatic ducts
Primary Sclerosing Cholangitis (PSC) management
Liver transplant- only proven treatment
Ursodeoxycholic Acid: unclear benefits
Haemochromatosis
Inherited disease (mostly autosomal recessive)characterised by excess iron deposition in various organs, leading to eventual fibrosis and functional organ failure
Haemochromatosis pathology
total iron content is v high (20-40g) vs normal person (3-4g). Iron content is particularly increased in the liver and pancreas (50-100x higher), but still higher in other organs
Haemochromatosis investigation
Serum iron/ ferritin elevated
Liver biochem often normal
genetic testing
Haemochromatosis management
Venesection- prolongs life and may reverse tissue damage- many initially to reduce iron to normal level, then a few a year
Screening- first degree relative need screened
Alpha1-antitrypsin deficiency
Results in inability to export alpha1-antitrypsin from liver. Neonatal jaundice, chronic liver disease in adults
Can lead -to liver disease (protein retention in liver)
-emphysema (protein deficiency in blood)
no medical treatment
Hepatocellular carcinoma
Primary liver tumour
Adenocarcinoma formed of cells resembling normal hepatocyte
Most occur in patients with cirrhosis
Hepatocellular carcinoma risk factors
Risk: highest for hepatitis B,C, haemochromatosis
lower: cirrhosis from alcoholic, autoimmune disease
Males >Females
Hepatocellular carcinoma presentation
May presents with decompensation of liver disease, weight loss ascites, or abdominal pain
Hepatocellular carcinoma treatment
Limited- Transplantation, resection or local ablative therapies
Sorafenib recently shown to prolong life
Non-alcoholic liver disease (NAFLD)
Includes Non-alcoholic fatty liver (NAFL) and Non-alcoholic steatohepatitis (NASH)
Commonest cause of chronic liver disease
Non-alcoholic fatty liver (NAFL)
Too much fat around liver
commonest cause of mildly elevated LFTs
Non-alcoholic steatohepatitis (NASH)
Fat around liver with inflammation, fibrosis
Important cause of cirrhosis(10-30% of patients develop cirrhosis)
NAFLD risk factors
Obesity (70%), DM (35-75%), hyperlipidaemia (20-80%)
NAFLD presentation
Usually asymptomatic, liver ache in 10%
How to distinguish between NAFL and NASH
Liver biopsy- inflammation present in NASH
NAFL treatment
Still no effective drug treatments
Weight loss works- the more the better
Hepatic vein occlusion
prevents blood from flowing out of the liver and back to the heart
Congestion causes acute or chronic liver injury
Hepatic vein occlusion causes
Thrombosis (Budd-Chiari syndrome)- may be underline thrombotic disorder
Membrane obstruction
Veno-occlusive disease (irradiation, antineoplastic drugs
Hepatic vein occlusion presentation
abnormal liver test, ascites, acute liver failure
Hepatic vein occlusion treatment
Anticoagulation
Transjugular intrahepatic portosystemic shunt
Liver transplantation
Causes of chronic liver disease
Alcohol
Non alcoholic steatohepatitis (NASH)
Viral hepatitis (B, C)
Immune- autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis
Metabolic-haemochromatosis, Wilsons, 1 antitrypsin deficiency…
Vascular- Budd-Chiari
Chronic liver disease- history taking
Past history: alcohol problems, biliary surgery, autoimmune disease, blood products
Social history: alcohol, sexual
Drug history (all drugs!!)
Family history
upper GI bleeding
a very common medical emergency, 10% mortality risk
Melena
Blood in stool, black and tary
Haematemesis
Fresh blood in vomit
Coffee ground vomiting
Old blood in vomit
Common cause of upper GI bleeding
Peptic ulcer (most common), oesophageal varices
Glasgow-Blatchford score
stratifies upper GI bleeding patients, uses BP, blood urea, haemoglobin levels, tachycardia, melaena, syncope, hepatic disease, cardiac failure
Variceal bleed- suspect history
liver disease or alcohol excess
Variceal bleed treatment
Antibiotics and Terlipressin (vasopressin agonist) reduce mortality.
Endoscopy within 12 hours
Non-variceal bleed- suspect history
peptic ulcers, using certain medications; NSAIDs, anticoagulation or antiplatelets
Non-variceal bleed
treatment
Consider proton pump inhibitors.
Endoscopy within 24 hours, longer than variceal
What has a bigger impact on patient survival for upper Gi bleeds, initial management or endoscopy
Initial assessment and management is more important than endoscopy in most cases
Difference in endoscopy treatment for variceal vs non variceal bleeding
Variceal- elastic band around bleed
Non-variceal- clipping bleed
Intraluminal intestinal obstruction
- tumour
– carcinoma
– lymphoma - diaphragm disease
- meconium ileus
- gallstone ileus
Tumours obstructing GI lumen
Can form in wall and grow inwards/outwards, growth inwards leads to obstruction of gut
Diaphragm disease
NSAIDs damage GI wall, mainly small bowel, fibrous ‘diaphragm’ scarring occludes the bowel lumen
Diaphragm disease- difficult to diagnosis
Normally small bowel, can not use endoscopy or colonoscopy, need to use swallowable camera
Gallstone ileus
mechanical intestinal obstruction due to impaction of one or more gallstones within the gastrointestinal tract
intramural obstruction
of GI tract
- inflammatory
– Crohn’s disease
– diverticulitis - tumours
- neural
– Hirschsprung’s disease
Crohn’s disease obstruction
Characteristic ‘cobblestone’ appearance
Diverticular disease
Infection in the tiny pouches in the colon. The pouches are called diverticula
Typically occurs in sigmoid colon
Can be asymptomatic, may need removal of sigmoid colon
Diverticular disease- pathophysiology
Holes in muscularis (for blood vessels), points of weakness, lots pressure in colon, force mucosa into points of weakness, mucosa out pouches through muscularis, called diverticula
Perpetrating Diverticulitis
Diverticulitis, breach of diverticula, contents spill into peritoneum, can lead to peritonitis
intramural tumours
tumours grow outwards, compress bowel wall, leading to occulsion
Hirschsprung’s disease
Congenital, due to missing nerve cells of muscle in colon
Part of bowel doesn’t move, causes obstruction
extraluminal obstruction of intestinal wall
- adhesions
- volvulus
- tumour
– peritoneal deposits
adhesions of intestine
Usually result of previous surgery, causes bands fibrous tissue between different parts of intestine
Can cause kink inn bowel
volvulus- intestine obstruction
Sigmoid colon twists on itself, causing obstruction
peritoneal tumour
Tumour growing in peritoneum compresses intestine, causing obstruction, problem in palliative care
Small Bowel Obstruction (SBO)
Mechanical blockage of the small
intestine
Small Bowel Obstruction (SBO)- expanded definition
a form of Intestinal failure (IF) is the inability of the gut to absorb
necessary water, macronutrients (carbohydrate, protein, and fat),
micronutrients, and electrolytes sufficient to sustain life and requiring
intravenous supplementation or replacement
Small bowel obstruction (SBO) Aetiology
Compression- Adhesions (typically have episodes), hernia, tumour
Luminal- growth, foreign, stricture
Lack of peristalsis- Drugs (commonly opioids), electrolytes, neurological, serve Ileus/ postop
Small bowel obstruction (SBO) symptoms
Colicky pain, absolute constipation (not passing of wind or stool), distension, vomiting
Small bowel obstruction patient history
History of preventing compliant- onset, previous episodes (chronic suggests cancer)?
Previous surgery (suggests adhesions)
Medication (opioids= lack of peristalsis, or drugs that alter electrolytes)
Family history- cancer
Social history- functional status for surgery evaluation
Small bowel obstruction (SBO)- clinical examination
Distended, tympanic, tender, hernias, bowel sounds (tinkling or absent), scars, PR
Small bowel obstruction (SBO)- consequences
Perforation, nutrition, GI vitality (necrosis), Gut barrier/ translocation (bugs in bloodstream, leading to sepsis), fluid losses
Small bowel obstruction (SBO)- investigation
CT scan, blood test (FBC, U+E, lactate- increases with poorly perfused gut, c-reactive protein)
Small bowel obstruction (SBO)- treatment for all patients
Decompression- nasogastric tube
Fluid replacement/ maintenance, electrolyte replacement, Nutrition (>5 without intake may
need parenteral feed)
Surgery- remove bit obstructed, remove adhesion
Barrett’s oesophagus
AKA CELLO- columnar lined lower oesophagus
Metaplasia due to presence of stomach acid in oesophagus destroying the squamous epithelium, leading to stem cells rising up from stomach producing glandular epithelium which is protected by mucin
Metaplasia
change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type
Barret’s oesophagus complications
Increase risk of oesophageal adenocarcinoma
Oesophageal
squamous cancer- risk factor
Smoking, high alcohol intake, not result of Barret’s oesophagus
Oesophageal symptoms that require urgent endoscopy
Acid reflux, pain, difficulty swallowing
Gastric cancer global spread
Eastern Asia and eastern Europe high, linked to poor air quality, smoked and pickled food
Helicobacter pylori and gastric cancer
Not always a cause, but can cause epithelium change in stomach to intestinal metaplasia, can lead to dysplasia and then carcinoma
linitus plastica
Thicken wall, whole stomach infected by cancer
Gastric cancer prognosis
Low survival rate (10-20% after 5 year), due to non-specific presentation
Why is small intestine cancer uncommon
Fluidity and relative sterility of small bowel contents, and rapid transit time and of the relative sterility of the small bowel itself have been suggested as possible factors
Colorectal cancer- risk factors
Most cancers arise from adenomas (dysplastic epithelium, most don’t turn into cancer), familial adenomatous polyposis (1% of colorectal cancer), hereditary nonpolyposis
colorectal cancer
Familial adenomatous polyposis
Born in normal colons, in teenage years form thousands of polyps in cancer, due to inherited genetic mutation
hereditary nonpolyposis colorectal cancer
(HNPCC)
a genetic disease of autosomal dominant inheritance. It is caused by a mutation in one of four genes of the DNA mismatch repair system
hereditary nonpolyposis colorectal cancer
(HNPCC)- reasons for identifing
risk of further cancers in index patient and
relatives
* possible implications for therapy
– tolerance of 5-FU etc.
– do not recognise DNA damage
– apoptosis not activated
macroscopic features
of colorectal cancer
38% of colorectal cancer (anus, rectum and rectosigmoid junction) can be felt on digital rectal examination
What is the most common colorectal tumour
adenocarcinoma
Treatment for colorectal cancer at each progression
Adenoma- endoscopic resection
Colorectal adenocarcinoma- surgical resection
Metastatic colorectal adenocarcinoma- chemo, palliative care
Hepatitis
inflammation of the liver
(acute< 6 months, chronic persists beyond 6 months)
Acute hepatitis- symptoms
None or non-specific, e.g. malaise, lethargy, myalgia
Gastrointestinal upset, abdominal pain
Jaundice + pale stools / dark urine
Acute hepatitis- clinical signs
Tender hepatomegaly ± jaundice
± signs of fulminant hepatitis (acute liver failure), e.g. bleeding, ascites, encephalopathy
Blood tests- Raised transaminases (ALT/AST»_space; GGT/ALP) ± raised bilirubin
Causes of acute hepatitis- infectious viral
Hepatitis A, B ± D, C & E
Human herpes viruses, e.g. HSV, VZV, CMV, EBV
Other viruses
Causes of acute hepatitis- infectious non- viral
Spirochaetes, e.g. leptospirosis, syphilis
Mycobacteria, e.g. M. tuberculosis
Bacteria, e.g. bartonella
Parasites, e.g. toxoplasma
Causes of acute hepatitis- non-infection
Drugs
Alcohol
Other toxins / poisoning
Non-alcoholic fatty liver disease
Pregnancy
Autoimmune hepatitis
Hereditary metabolic causes
Chronic hepatitis symptoms
Can be asymptomatic or have non-specific symptoms only
chronic hepatitis- clinical signs
Clubbing, palmar erythema, Dupuytren’s contracture, spider naevi, etc
Transaminases (ALT/AST) can be normal
chronic hepatitis- clinical signs compensated
liver function maintained
chronic hepatitis- clinical signs decompensated
coagulopathy (↑PT, INR); jaundice (↑bilirubin); low albumin; ascites (± bacterial peritonitis); encephalopathy
chronic hepatitis- complications
hepatocellular carcinoma (HCC); portal hypertension (varices, bleeding)
chronic hepatitis- causes, infection
Hepatitis B ± D, C (& E)
chronic hepatitis- causes, non- infection
Drugs
Alcohol
Other toxins / poisoning
Non-alcoholic fatty liver disease
Autoimmune hepatitis
Hereditary metabolic causes
Most common form of viral hepatitis
chronic hepatitis B ≈ 257 million
then, chronic hepatitis C ≈ 71 million
Hepatitis A (HAV)
Contaminated food & water
Linkage to access to safe drinking water & socioeconomic indicators
HICs- travel, MSM (men sex with men), IV drug use
Hepatitis A: Clinical
Short incubation period (15-50 days), acute
Symptomatic
Rarely acute liver failure
100% immunity after infection
Hepatitis A: symptoms
Symptomatic- Pre-icteric phase: constitutional symptoms + abdominal pain
Icteric phase (few days to 1 week after pre-icteric phase)
Hepatitis A: serological response
anti- HAV IgM initially, anti-HAV IgG provide immunity
Hepatitis A: Management
Supportive
Monitor liver function
Primary prevention- vaccines
Liver function measures
INR, albumin, bilirubin
hepatitis E
4 genotypes- affect different parts of world
G1+2- similar to HAV, transmission through food and water
G3+4- undercooked meat
Hepatitis E: Clinical
> 95% cases asymptomatic
Usually self-limiting acute hepatitis
Extra-hepatic manifestations (neurological)
Chronic Hepatitis E
Risk of chronic infection (GT3/4 only) in immunosuppressed patients
e.g. transplant recipients, HIV patients
rapid progression to cirrhosis
Hepatitis E: serological response
anti-HEV IgM initially, partial immunity from anti-HEV IgG
Hepatitis E: Management
Acute- supportive, monitor for acute-on-chronic liver failure
Chronic- Reverse immunosuppression (if possible)
If HEV RNA persists, treat with ribavirin ≥ 3 mths
Hepatitis E: Prevention
Avoid eating undercooked meats (especially if immunocompromised)
Screening of blood donors
Vaccines in development
hepatitis B
Blood-borne virus
Transmission via blood and body fluids
Hepatitis B natural history adults !!!!!
Acute HBV infection
Symptomatic- Spontaneous resolution (rick of re-activation with immunosuppression
Chronic HBV infection- asymptomatic Cirrhosis> Hepatocellular carcinoma or Decompensated cirrhosis
Hepatitis B natural history (neonates and infants)
Hepatitis B: serological response
!!!
anti-HB core IgG- exposure to HBV infection
Hepatitis B surface antigen- Current HBV infection
Acute Hepatitis B: presentation & management
Incubation period: 30 to 180 days (mean 75 days)
Supportive management
Monitor liver function (INR, albumin, bilirubin, etc.)
Rarely fulminant hepatitic failure: 0.1 to 0.5%
Oral nucleos(t)ide analogue (tenofovir, entecavir)
Liaise with hepatology / liver transplant centre
Management of close contacts (HBV vaccine if non-immune ± HBIG )
Hepatitis B: clearance in acute phase
Hepatitis B: failure to clear / chronic infection
Chronic hepatitis B: who to treat?
!!!!!
e-antigen (eAg)- high viral load
e-antibody (eAb)- high immune response
Treat people in immune reactive and immune escape stage
Chronic hepatitis B- treatment- pegylated interferon-α 2a
Immunomodulatory
stimulates immune response
Weekly subcutaneous injection
48 week long treatment course
Offers best chance of treatment-free control
Side effects & need for monitoring
pegylated interferon-α 2a side effects
Chronic hepatitis B- treatment- oral nucleos(t)ide analogues
Inhibit viral replication
HBV DNA polymerase
One tablet once a day
High barrier to resistance
Minimal side effects
Renal monitoring (TDF)
May be required lifelong
Hepatitis B: Prevention
Antenatal screening (HBsAg testing) of pregnant mothers
Screening ± immunisation of sexual and household contacts
Childhood immunisation
Universal screening of blood products
Hepatitis D
Defective RNA virus
Requires Hep B antigen presence to replicate
Blood-borne virus
Transmission via blood and body fluids
Hepatitis B + D coinfection
Infected by hep B + D together, increased risk of fulminant hepatitis in acute infection
Hepatitis B + D superinfetion
Infected by hep B, then hep D, acute on chronic hepatitis
accelerated progression to liver fibrosis
Hepatitis B + D coinfection natural history
Hepatitis D test
Hepatitis D antibody: if positive, test HDV RNA
Hepatitis D treat
pegylated inteferon-α 48 weeks (2020: Myrcludex B)
Hepatitis C
Blood-borne virus
Transmission via blood and body fluids- IV drug use, blood products
Hepatitis C natural history (immunocompetent adults)
!!!
Hepatitis C testing
HCV antibody
If +ive, HCV RNA (to see if infection is active)
If +ive, HCV genotype (to determine type of HCV)
Hepatitis C treatment- Directly-acting antiviral (DAA) therapy
Combination of antivirals
Drugs have different effects on different genotypes (need to know genotype)
Hepatitis C: Prevention
No vaccine
Previous infection does not confer immunity
Blood screening
Cure of ‘transmitters”, ie programs to reduce IV drug use
Coeliac disease
Autoimmune entropy caused by ingestion of gluten
1/4 are genetically predisposed to disease
Coeliac disease management
Gluten free diet- strict and lifelong
Dietitian review
Bone density score
Prescription of GF foods
Immunisation
Coeliac disease symptoms
severe diarrhoea, excessive wind and/or constipation.
persistent or unexplained gastrointestinal symptoms.
iron, vitamin B12 or folic acid deficiency.
anaemia.
tiredness
Coeliac disease associated diseases
Addison’s Disease
Arthritis
Autoimmune Hepatitis
Hashimoto’s Thyroiditis
Idiopathic Dilated Cardiomyopathy
IgA Nephropathy (Berger’s Disease)
Multiple Sclerosis (MS)
Sjogren’s Syndrome
Type 1 Diabetes Mellitus
Mucosal Ischemia
Ischemia of blood vessels that supply mucosal layer of stomach, leads to reduce mucin layer and can lead to an ulcer
Common with people with in haemodynamic shock
Mucosal Ischemia - treatment
Reverse the mucosal ischemia- cell revert back to normal
PPIs/ H2 blockers to remove acid
Causes of gastric ulceration
NSAIDs, Helicobacter pylori (H. pylori), mucosal ischemia, bile reflux, alcohol (high percentage spirits)
Helicobacter pylori (H. pylori)
Live in mucin layer in stomach, can lead to acute inflammation, long term helicobacter can cause intestinal metaplasia
Causes of malabsorption
Insufficient intake, defective intraluminal digestion, insufficient absorptive areas, lack of digestive enzymes, defective epithelial transport, lymphatic obstruction
Causes of malabsorption- Defective intraluminal digestion
Pancreatic insufficiency (CF, pancreatitis), Defective bile secretion (lack of fat solubility- biliary obstruction, ileal resection), Bacterial overgrowth
Causes of malabsorption- Insufficient absorptive areas
Coeliacs disease, Crohn’s disease, extensive parasitic infection (giardia lamblia), small intestinal resection or bypass
Causes of malabsorption- lack of digestive enzymes
disaccharidase deficiency (lactose intolerance- disaccharide broken down in small intestine, causes large release of CO2 and sugars causes diarrhoea), bacterial overgrowth
Causes of malabsorption- defective epithelial transport,
Abetalipoproteinemia, primary bile acid malabsorption (mutations in bile acid transporter protein)
Gallstones types
Cholesterol, pigment stones (bile acid, phosphate, Mg) + mixed stones
Commonest type of gallstones
Cholesterol stones
Biliary anatomy
Liver produces bile
Gallbladder stores bile
Responds to CCK
Biliary system drains into D2 (Ampulla of Vater)
Gallstones- 5 Fs
fat, female, forty, fertile, fair (skin/ hair)
Gallstones pathology
Biliary colic, jaundice, pancreatitis, cholecystitis (stone in stone bladder), choledocholithiasis (stones in bile duct), Cholangitis, Gallstone ileus, Mirizzi syndrome (stone in impacted in Hartman pouch)
Biliary colic signs + symptoms
Post prandial colicky pain (worse with fats, RUQ), nausea/ vomiting,
cholecystitis signs and symptoms
Constant pain, fever, rigours, tender as inflamed gallbladder contacting peritoneum
choledocholithiasis signs and symptoms
jaundice
Cholangitis signs and symptoms
Fever >39, jaundice
Gallstones investigations
Ultrasounds (USS), FBC, LFTs (alkaline phosphates, ALT, bilirubin, albumin), Clotting factors, amylase (pancreatic damage), MRCP (MRI of bile system)
Mirizzi syndrome
Gallstone Ileus
a mechanical intestinal obstruction due to impaction of one or more gallstones within the gastrointestinal tract
Gallstones treatment
Antibiotics, analgesia- NSAIDs with PPI cover, ECRP (to remove stone from bile duct), cholecystectomy, bile duct exploration/ reconstruction (surgical removal of stone)
Pancreatitis- I GET SMASHED
Idiopathic, Gallstones, Ethanol, Trauma. Steroid use, Mumps, Autoimmune, Scorpion stings, Hypercalcemia + hypertriglyceridemia, ECRP, Drugs
Most common cause of pancreatitis in England
Gallstones
Pancreatitis- signs and symptoms
Abdominal pain that radiates to the back, Nauseas/ vomiting, Low BP, high HR/ RR, low SATS, high temp
Pancreatitis complications
Auto digestion, SIRS
Pancreatitis complications- Auto digestion
Haemorrhage, pseudoaneurysm, portal thrombosis, necrosis, infected necrosis, pseudocyst
Pancreatitis complications- SIRS*****
ARDS,
Pancreatitis- severity score
Modified Early Warning Score (MEWS), good history, response to resuscitation
Modified Early Warning Score (MEWS)
HR, BP, RR, core body temp, mental status and urine output
Pancreatitis treatment
Supportive (fluids, nutrition, antibiotics, critical care), ECRP (to remove stones from bile duct), Cyst drainage, treat pancreatic failure for both exocrine (replace enzymes) and endocrine (diabetic) function
Chronic pancreatitis
Flares of pancreatitis with or without trigger, pain, malnutrition, pancreatic duct strictures, may need drainage procedure or total pancreatectomy
Chronic idiopathic inflammatory bowel disease (CIIBD)
Crohn’s disease, Ulcerative colitis
Crohn’s disease
Transmural, non continuous inflammation that can occur anywhere in the GI tract
Characteristic Crohn’s disease appearance
Scarring causes ‘cobblestone’ appearance
Main complications of Crohn’s disease
Mainly affects bowel, malabsorption, obstruction, perforation, fistula formation, neoplasia
Ulcerative colitis
Only affects mucosa, starts at the rectum and is continuous inflammation, working up the bowel
Ulcerative colitis complications
Affects many different parts of the body, Colon, joints, eyes, skin, liver
CIIBD- aetiology
Currently unknown
Function of Peritoneum- In health
Visceral lubrication
Fluid & particulate absorption
Function of Peritoneum- In disease
Pain perception.
Inflammatory and immune responses
Fibrinolytic activity
Which is more sensitive to pain (from pressure, temp and laceration) visceral or parietal peritoneum?
Parietal peritoneum
Peritonitis
Inflammation of Peritoneum
Peritonitis : Classification- onset
Acute : Sudden Onset. Eg Bacterial
Chronic : Gradual Onset . Eg TB
Peritonitis : Classification- Source of origin
Primary : No documented Source
Secondary : Bowel Perforation, Appendicitis
Peritonitis : Aetiology
Bacterial, gastrointestinal and non-gastrointestinal
Chemical, e.g. bile, barium
Traumatic, e.g. operative handling
Ischaemia, e.g. strangulated bowel, vascular occlusion
Miscellaneous, e.g. familial Mediterranean fever
Paths to Peritoneal Infection
Gastrointestinal perforation
Transmural translocation (no perforation)
Exogenous contamination
Female genital tract infection, e.g. pelvic inflammatory disease
Haematogenous spread (rare), e.g. septicaemia
Paths to Peritoneal Infection- Transmural translocation
Pancreatitis, ischaemic bowel, primary bacterial peritonitis
Paths to Peritoneal Infection- Gastrointestinal perforation
Perforated ulcer, appendix, diverticulum
Paths to Peritoneal Infection- Exogenous contamination
drains, open surgery, trauma, peritoneal dialysis
Clinical feat. of localised peritonitis
Pain
Nausea and vomiting
Fever
Tachycardia
Localised guarding
Rebound tenderness
Shoulder tip pain ( subphrenic)
Tender rectal and / or vaginal examination (pelvic peritonitis).
Diffuse (generalised) peritonitis- Early
Abdominal pain (worse by moving or breathing)
Tenderness
Generalised guarding
Infrequent bowel sounds (paralytic ileus)
Fever
Tachycardia
Diffuse (generalised) peritonitis- Late
Generalised rigidity
Distension
Absent bowel sounds
Circulatory failure
Thready irregular pulse
(Hippocratic face)
Loss of consciousness
Peritonitis- Investigations
Urine dipstix for urinary tract infection.
ECG if diagnostic doubt (as to cause of abdominal pain) or cardiac history.
Bloods I U&Es I Full blood count (WCC)
Serum amylase (acute pancreatitis/ others like perf duodenal ulcer)
Medical management of peritonitis
Correction of Fluid Loss & Circulating Volume
Antibiotics
Urinary Catheterisation I Gastric Decompression
Analgesics
Surgical treatment of peritonitis
Remove or divert cause:
Repair of perforated viscus – peptic ulcer
Excision of perforated organ
With or without drainage
With or without restoring continuity
Peritoneal lavage
Ascites
Detectable collection of Fluid in the peritoneal cavity
Chronic accumulation of Fluid within the peritoneal cavity
Ascites- Classification
Stage 1 detectable only after careful examination / Ultrasound scan (Mild)
Stage 2 easily detectable but of relatively small volume.
Stage 3 obvious, not tense ascites. (moderate)
Stage 4 tense ascites. (Large)
Refractory ascites
not mobilised
or early recurrence (after therapeutic paracentesis) <4 weeks
Cannot be prevented by medical therapy
Diuretic resistant ascites
refractory to dietary sodium restriction and intensive diuretic treatment
Diuretic intractable ascites
ascites that is refractory to therapy due to the development of diuretic induced complications that preclude the use of an effective diuretic dosage
Ascites - Causes
Cirrhosis- 75%, main cause
Malignancy- 10%
Heart failure, TB, pancreatitis
Ascites malignancy causes
gynecologic neoplasms gastrointestinal malignancies
breast cancer
Ascites - Portal Hypertension
- Pathophysiology
A state of sodium water imbalance
Interplay of various neurohormonal agents – renin, aldosterone, sympathetic nervous system, nitric oxide
Ascites -Non Portal hypertension- Pathophysiology
Malignancy
Cardiac Failure
Nephrotic syndrome
Ascitis in Liver Cirrhosis - Pathophysiology
Portal Hypertension
Shunting of Blood into the systemic Circulation
Splanchnic Vasodilation (release of vasodilators NO)
Systemic Blood Pressure falls due to vasodilation
Renal Hypoperfusion
Activation of RAAS
Increased Na & H20 Retention by kidney
Increased Plasma Hydrostatic Pressure
Increased Transudation of fluid in Peritoneal Cavity
Ascites
Exudative Ascites
Occlusion / obstruction of lymphatic /venous drainage
Ascites Protein Concentration above 25 gm/l
Transudative Ascites
passage of fluid through a membrane – osmotic pressure, hydrostatic pressure
Protein concentration below 25 gm/l
Ascites- Exudate causes
Congestive cardiac failure
Constrictive pericarditis
Nephrotic syndrome
Myxoedma
Bud Chiari Syndrome – Hepatic venous thrombosis
Chylous ascites
Ascites- Transudate causes
Cirrhosis
Hypoproteinemic states
-Protein losing enteropathy
-Malnutrition
-Tuberculosis ( minority)
-Malignancy ( minority)
Ascites RF in history
Relating to liver disease- long term heavy alcohol consumption, infection (chronic viral hep, IV drug use, travel)
-Non-alcoholic steatohepatitis (Cirrhosis, DM type 2
Obesity, Hypercholesterolemia)
GI/ ovarian cancer
Cardiac
Renal- nephrotic syndrome
Malnutrition- selective protein deficiency
Ascites- Clinical Presentation - Symptoms
Abdominal distension
Clothes getting tighter
? Gaining wait
Nausea, Loss of appetite
Constipation
Cachexia- wasting ? weight loss
Pain / Discomfort
Present – malignant
Absent – non malignant
Associated symptoms of underlying cause
Ascites- Clinical Presentation - Signs
Abdominal distension
Fluid thrill
Jaundice and other stigmata of liver disease (If liver causse of disease)
Ascites- diagnosis- analysis of ascitic fluid
Naked eye assessment
Chemistry
-Proteins
-Amylase
Microscopy
-Cytology
-Organisms
Culture
Ascites- diagnosis- Naked eye assessment of ascitic fluid
Most ascitic fluid is transparent and tinged yellow
Pink/ blood tinged fluid implies trauma or malignancy
Cloudy fluid with a purulent consistency indicates infection
Ascites- diagnosis- radiology
X-Ray ( 500ml)
Ultra sound scan ( at least 20ml)
CT abdomen (< v small amt)
Ascites- diagnosis- Serum Ascites Albumin Gradient [SAAG]
Serum albumin - ascites albumin
Value 1.1 g/dl important cut off ( 97% accuracy)
>1.1 g/dl – Portal hypertension
<1.1 g/dl – non portal hypertensive cause
Ascites treatment
*Treatment of underlying cause
*Portal hypertension- salt and fluid restrictions, diuretics, albumen/ colloid replacement
*Paracentesis
*Shunts
-Portosystemic shunts (liver cirrhosis)
-Peritoneovenous shunt- for patients with medically intractable ascites
Ascites treatment- portal hypertension
Salt and Fluid restriction
Diuretics
Albumen / colloid replacement
Paracentesis
procedure performed in patients with ascites, during which a needle is inserted into the peritoneal cavity to obtain ascitic fluid
Crohn’s disease treatment- general
No curative treatment
Aims to induce/maintain clinical remission
Crohn’s disease treatment- Induce remisson
Glucocorticosteroids- 1st line
Early Anti-TNF agents- for patients with poor prognosis
Management of extra-intestinal symptoms
Consider antibiotics
Crohn’s disease treatment- Maintain remission
Azathioprine, mercaptopurine + methotrexate- conventional maintenance therapies
Anti- TNF agents + novel biological therapies
Crohn’s disease treatment- surgical management
Indication for surgery- failure of medical therapy, complications, presence of perianal sepsis
Strictureplasty- to widen strictures
Subtotal Colectomy + Ileorectal anastomosis- if CD involves all of Colon and minimally rectum
Panproctocolectomy with an end ileostomy- if CD involves all of colon and rectum
Crohn’s disease investigations
Blood tests (FBC, iron studies+ serum folate/B12, CRP and ESR)
Stool tests (Stool cultures including C. difficile toxin assay, faecal calprotectin- raised in active intestinal inflammation
Imaging (MR enterography > CT enterography)
Colonoscopy with biopsies (2 from 5 different locations)
Upper GI endoscopy for patients with relevant upper GI symptoms
Crohn’s disease investigations- blood tests
FBC- Anaemia, leucocytosis, may be thrombocytosis: all signs of inflammation
Iron studies- may be normal, or may demonstrate changes consistent with iron deficiency due to malabsorption or GI bleeding
Raised C-reactive protein (CRP) + erythrocyte sedimentation rate (ESR)- Inflammatory markers
Crohn’s disease investigations- colonoscopy
Aphthous ulcers, hyperaemia, oedema, skip lesions
Characteristic cobblestone appearance
Ulcerative colitis investigations
Blood tests (FBC, ESR + CRP, comprehensive metabolic panel including LFTs)
Stool tests (Stool cultures including C. difficile toxin assay, faecal calprotectin- raised in active intestinal inflammation)
Endoscopy with mucosal biopsy is gold standard- flexible sigmoidoscopy/ colonoscopy
Abdominal X-ray- patients in acute severe UC attacks to exclude colonic dilation
Ulcerative colitis investigations- blood tests
FBC- may show leukocytosis, thrombocytosis, and anaemia
Raised ESR + CRP- inflammatory markers
Comprehensive metabolic panel- should be checked every 6 to 12 months for surveillance of primary sclerosing cholangitis
Ulcerative colitis investigations- flexible sigmoidoscopy/ colonoscopy
rectal involvement, continuous uniform involvement, loss of vascular marking, diffuse erythema, mucosal granularity, fistulas (rarely seen), normal terminal ileum (or mild ‘backwash’ ileitis in pancolitis)
Ulcerative colitis treatment- medical management
Induce/ maintain remission
Aminosalicylate are mainstay treatment- effective at maintaining remission and inducing remission for mild to moderate active disease
Ulcerative colitis treatment- refractory/ severe colitis
Investigated to confirm active colitis and exclude infection
Biological therapy with anti- TNF agent/ anti-integrin agent
Corticosteroids- initially oral prednisolone, if ineffective hospitalization with IV hydrocortisone and supportive treatment
If IV steroids ineffective after 3 days, either surgery or salvage medical therapy
Ulcerative colitis treatment- surgery
Curative, but reduces QoL
Acute disease- Subtotal colectomy with end ileostomy, preservation of rectum is operative choice
More surgical options available at later date; proctectomy with a permeant ileostomy or ileo-anal pouch (1/3 of patients experience pouchitis)
Functional Gastrointestinal Disorders (FGIDS)
Chronic GI symptoms in the absence of organic disease to explain the symptoms
Also termed “disorders of gut-brain interaction”
ie IBS, functional dyspepsia
Disorders of Gut-Brain Interaction
A group of disorders, classified by GI symptoms, related to any combination of: visceral hypersensitivity, motility disturbances, altered CNS processing, gut microbiota, mucosal and immune function
Irritable Bowel Syndrome (IBS)
Affects 10% of pop
Chronic frequent abdominal pain, Altered bowel habit, Bloating commonly associated
Dyspepsia
affects 10% of the population
Functional dyspepsia (~80%)
Organic dyspepsia (~20%)
Alarm features or Red Flags for GI disease
- Age >45 years
- Short history of symptoms
- Documented unintentional weight loss
- Nocturnal symptoms
- Family history of GI cancer/IBD
- GI Bleeding
- Palpable abdominal mass or lymphadenopathy
- Evidence of iron deficiency anaemia on blood testing
- Evidence of inflammation on blood/stool testing
Faecal Calprotectin
Marker of GI inflammation
Found in UC and CD, not in IBS
Wernicke’s encephalopathy
Thiamine (vitamin B1) deficiency with classic triad of confusion, ataxia and ophthalmoplegia (nystagmus, lateral rectus or conjugate gaze palsies)
Wernicke’s encephalopathy- causes
Chronic alcoholism, eating disorders, malnutrition, prolonged vomiting
Wernicke’s encephalopathy- management
Diagnosis is primarily clinical
Urgent thiamine replacement via IV/IM then oral supplement until no longer at risk
Gilbert’s syndrome
Common cause of unconjugated hyperbilirubinemia due to decrease UGT-1 activity (enzyme that conjugates bilirubin)
Gilbert’s syndrome- diagnosis
Mild increased bilirubin, normal FBC and reticulocytes (normal haemolysis)
Gilbert’s syndrome- presenation
May go unnoticed for years and usually presents in adolescence with intermittent jaundice occurring during illness, exercise or fasting
Pancreatic cancer
Most common presentation is at 65-75 years of age with painless obstructive jaundice and weight loss. Generally presents late with advanced disease.
Pancreatic cancer- pathology
Mostly ductal adenocarcinoma which metastasize early and present late
Ampullary or islet cell
tumours are rarer but better prognosis
Pancreatic cancer- RFs
Smoking, alcohol, carcinogens, DM, chronic pancreatitis, high waist circumference, hight fat/red meat diet
Pancreatic cancer- signs
Jaundice + palpable gallbladder, epigastric mass, hepato/ splenomegaly, lymphadenopathy, ascites, weight loss + anorexia
Pancreatic cancer- Investigations
pancreatic protocol CT
abdominal ultrasound
LFTs (show degree of obstructive jaundice)
Pancreatic cancer- Appearance on abdominal imaging
Pancreatic mass +/- dilated biliary tree +/- hepatic mets
Pancreatic cancer- Management
Based on extent of disease, given most present late, a lot of treatment is palliative (ie surgery to relive symptoms, chemo to delay disease progression)
Pancreatic cancer- prognosis
Mean survival <6 months
5 years survival is 3%
Prognosis better if clear margins during surgery, use of whipple procedure or if tumour is ampullary or islet cell
