32 Flashcards
GI and Surgery
Epidemiology UC
- Incidence: 21 per 100,000
- Prevalence: 240 per 100,000
- Occurs more in Caucasians and Ashkenazic Jews
- F:M ratio 1:1
- Peak incidence in 15-25 and 55-65 years
- Can present in very young children or elderly
S+S of UC
Relapsing and remitting in nature Diarrhoea PR bleeding Frequency of stools, associated with urgency Fatigue and malaise Fever Mucus discharge
Tachycardia
Fever
Abdominal tenderness
Disease features of UC
Only affects the colon, always affects the rectum.
Inflammation limited to the mucosa.
Mucosal atrophy, walls appear thin.
Ulcers are superficial with a broad base.
Malignant potential.
Negatives: No skin lesions. No mural thickening, no strictures, no fistulas. No malabsorption . No recurrence post-op.
Pathophysiology of UC
Defects in host interaction with intestinal bacteria.
Intestinal epithelial dysfunction.
Inappropriate mucosal immune responses.
TH17 and TH2 are increasingly active.
Defects in epithelial tight junctions increased passage of bacteria to cause a reaction.
Increased cytokine activity.
No specific gene.
Investigations for UC
FBC - anaemia or thrombocytosis.
LFTs - raised ALP, hypoalbuminaemia, hypokalaemia, hypomagnesaemia.
Raised ESR and CRP.
Test iron, B12, folate.
Foetal calprotectin, usually used for monitoring.
Stool samples for infection,
ANCA positive
Colonoscopy/sigmoidoscopy + biopsy - abnormal erythematous mucosa with ulceration - biopsy for confirmation
Abdominal X-ray to check for perforation.
Double contrast barium enema - lead piping
Foetal calprotectin, usually used for monitoring
Can use CT enterography
Measuring severity of UC
Using Truelove and Witt’s severity index
MILD - diarrhoea <4 times /day, no anaemia, no fever, no tachycardia, no weight loss.
MODERATE - diarrhoea 4/5 times per day, Small amount of blood in stool, no fever, no tachycardia, raised CRP (mild).
SEVERE - diarrhoea 6+ times a day, blood in stool, fever, tachycardia, anaemia, raised CRP.
Extracolonic manifestations of UC
Uveitis Pleuritis Erythema nodosum Ankylosing spondylitis Pyoderma gangrenosum
Primary sclerosing cholangitis
MS
Management of UC - inducing remission
- Amniosalicylates - mesalazine
- Corticosteroids - oral prednisolone
- Immunomodulators - azathioprine, methotrexate, ciclosporin
- Mabs - Infliximab in severe cases
- Surgery
Complications of UC
- Haemorrhage
- Toxic megacolon
- Colorectal carcinoma
- Fatty liver
- Primary sclerosing cholangitis
Epidemiology of Crohn’s
- Genetic link - NOD2
- Smoking is a big risk factor
- Most common in ileocaecal region
- Incidence: 4 per 100,000
- Prevalence: 150 per 100,000
- Caucasians and Ashkenazic Jews
- F:M ratio 1.5:1
- Peak incidence in 15-25 and 50-80 years
- More common in smokers
- Can occur in children (usually with FHx)”
Symptoms of Crohn’s
Diarrhoea PR bleeding Abdominal pain Weight loss Fatigue Mouth ulcers
Features of Crohn’s
Any part of GI tract.
Transmural, can form strictures.
Skip lesions.
Oedema and loss of mucosal texture.
Triggered by emotional stresses or smoking.
Cobblestone appearance.
Ulcers deep and knife like.
Fistulas common.
Fat/vitamin malabsorption.
Malignant potential if in colon.
Recurrence post-op is common.
40% ileocecal, 30% small intestine, 25% colon
Pathophysiology of Crohn’s
Defects in host interaction with intestinal bacteria
Intestinal epithelial dysfunction
Inappropriate mucosal immune responses
TH17 and TH2 are increasingly active
Defects in epithelial tight junctions increased passage of bacteria to cause a reaction
Increased cytokine activity
NOD 2 gene
Investigations in Crohn’s
FBC - anaemia
Raised CRP
Nutrient deficiency, B12, folate
LFTs hypoalbuminaemia
Stool culture for C.diff
ASCA (not ANCA as in UC)
Endoscopy - ileocolonoscopy + biopsies, occasionally OGD
Abdominal X-ray for perforation
Small bowel follow through - cobblestone appearance
Can have CT enterography
Management of Crohn’s - inducing remission
- Steroid - prednisolone
- Aminosallicylate - mesalazine
- Azathioprine / mercaptopurine
- Methotrexate
- Infiximab or adalimumab
Surgery is last line
Management of Crohn’s - maintenance
Azathioprine or mercaptopurine
Extraintestinal features of Crohn’s
Uveitis Migrating polyarthritis Ankylosing spondylitis Clubbing Pyoderma gangrenosum (greater incidence than in UC) Erythema nodosum Aphthous ulcers
Classification of Crohn’s disease
Crohn’s disease activity index:
<150 remission, 150-300 active, 300+ severe.
Depends on number of stools, pain, well being, extra intestinal manifestations, pyrexia, etc.
Harvey Bradshaw Index
<4 = remission, 5-8 moderate, 8+ severe
19
Complications of Crohn’s
- Malabsorption (short loop/bowel syndrome due to repeated resection)
- Stricturing
- Anal lesions (60%): fissures, fistula
- Perforation
- Cholelithiasis
- Fatty liver
- Increased risk of malignancy of SI but less frequent than ulcerative colitis
Causes of upper GI bleeding
Gastritis - dyspepsia
Oesophagitis - dyspepsia , worse on lying
Gastric/duodenal ulcer - nausea, vomiting, weight loss, dyspepsia
Oesophageal/gastric varices - Hx of liver disease, alcohol excess
Cancer - malaise, weight loss, vomiting, early satiety
Mallory-Weiss tear = young, history of vomiting, small amounts
Gastric/duodenal erosions = NSAID or alcohol history, epigastric pain
Drugs = aspirin, NSAIDs, steroidsm thrombolytics, anticoagulants
Rare = bleeding disorders, aorto-enteric fistula, Meckel’s diverticulum
Symptoms and signs of upper GI bleeding
Fresh haematemesis or coffee grounds
Melaena
Medication and alcohol history
Tachycardic and hypotensive
Cap refill may be reduced
Postural BP drop
Anaemia - pallor
Stigmata of liver disease - hepatic flap, caput medusa, ascites, hepatomegaly, spider naevi
Investigations for GI bleeding
FBC - haemoglobin and MCV (if low MCV, may be chronic).
U+E - raised urea to creatinine ratio.
LFTs - clotting and signs of chronic liver disease.
Upper GI endoscopy - NBM for 4 hours.
Classification of GI bleeds
Rockall risk scoring:
- relies on BP, HR, endoscopy
Low risk - 0-1, moderate 2-3, severe 4+
Blatchford score:
No endoscopy required
Predicts who needs intervention - 6+ needs intervention
Management of upper GI bleed
Non-variceal:
- Resuscitate
- Endoscopy within 4/24 hours, urgent/non-urgent, no routine PPI pre-endoscopy
Variceal:
- Resuscitate
- Terlipressin
- Variceal band, ligation/adrenaline injections/ TIPS/ glue
- Balloon tamponade (Sengstaken-Blakemore tube)
- Antibiotics
Side effects of blood transfusions
Hypothermia as products stored at fridge temperature.
Hypocalcaemia - blood contains citrate which chelates calcium.
Hyperkalaemia.
Causes of lower GI bleeding visible
Haemorrhoids Fissures Carcinoma Polyps Proctitis Diverticular disease IBD Angiodysplasia Infection - E.coli, shigella, salmonella, campylobacter
Investigations for lower GI bleeding visible
FBC U+Es Clotting LFTs Colonoscopy or flexible sig Rectal exam Stool cultures
Causes of occult GI bleeding
Coeliac disease Gastric cancer Peptic ulcer disease Colorectal cancer IBD
Management of occult GI bleeding
Treat underlying cause.
Replace iron stores if deficient.
Check blood count after 1 month to see if it improves.
Signs, symptoms and deficiency states for fat soluble vitamins
A
- Night blindness
D
- Osteomalacia
- Proximal limb weakness
E
- Anaemia
K
- Clotting deficiency
- Bruising
Signs, symptoms and deficiency state for vitamins B6, B12, C and folate
B6
- Dermtitis
- Anaemia
B12
- Pernicious anaemia
- Tired/fatigue/pale
- Peripheral neuropathy
Folate
- Megaloblastic anaemia
- Tired/fatigue/pale
C
- Scurvy
- Bruising
- Gingivitis
Reasons for malnutrition in hospitals
Secondary to pathological disease - raised metabolic demand
Neglect - by patient or staff
NBM
Who should receive nutritional support in hospitals?
- BMI < 18.5
- Unintentional weight loss >10% in 3-6 months.
- BMI < 20 and unintentional weight loss >5% in 3-6 months.
- Eaten little or nothing for 5 days and not likely to in next 5 days.
- Poor absorptive capacity.
Methods of enteral feeding
Oral - supplementation e.g, fortisips.
Tube feeding - NG tube if inadequate or unsafe oral intake.
Enterostomy feeding - if for over 4-6 weeks.
PEG tube - can get perforation, infection or peritonitis.
Parenteral feeding
Only if other routes not suitable e.g. perforated GI tract.
If short term can use peripheral cannula <14 days.
If not the PICC line.
Complicated by thrombophlebitis.
Refeeding syndrome
Complication from too rapid reintroduction of feeding following starvation.
Process:
- Low insulin levels secondary to starving.
- When feeding restarted, increased insulin.
- Insulin causes cellular uptake of phosphate
- Low phosphate causes respiratory/cardiac failure, muscle weakness, seizures, coma.
Usually occurs in day 4 of refeeding.
Which patients are at high risk of refeeding syndrome?
BMI < 16
History of alcohol abuse
Little or no intake for 10 days
Low levels of phosphate, potassium or magnesium prior to feed
Unintentional weight loss of >15% in last 3-6 months
Clinical features of malabsorption
Diarrhoea Steatorrhoea Weight loss Fatigue Flatulence and abdominal distension Oedema from hypoalbuminaemia Bleeding disorders (vit K) Metabolic defects in bones Neurological manifestation (low Ca, Mg - tetany)
Orthostatic hypotension Decreased subcut fat Signs of muscle loss or wasting Hyperactive bowel sounds Ascites Pallor Peripheral oedema Glossitis
Causes of microcytic hypochromic anaemia
LISTS:
Lead poisoning
Iron-deficiency - blood loss, increased demand (growth and pregnancy), decreased absorption (post-gastrectomy, Crohn’s), poor intake.
Sideroblastic
Thalassemia
Sickle cell
Causes of normocytic normochromic anaemia
HAHAC:
Haemolytic Acute blood loss Hypersplenism Aplastic – bone marrow infiltration CKD
Causes of macrocytic anaemia
PPMATRC:
Pregnancy
Pernicious – intrinsic factor def leading to B12 deficiency
Megaloblastic – B12 / B9 deficiency:
B12 - gastrectomy, ileal disease, resection.
B9 - alcohol, coeliac, Crohn’s, partial gastrectomy, cancer, drugs.
Alcoholism
hypoThyroidism
Reticulocytosis
Cirrhosis – liver disease
Clinical features of anaemia
Fatigue Headache Angina Breathlessness Pallor Palpitations Tachycardia
Epidemiology of coeliac disease
Increased in females (2 to 1)
Age peaks in early childhood and again 40-50
1-2% prevalence
FHx - HLA DQ2
RF - other autoimmune disease
Signs and symptoms of coeliac disease
Tiredness, malaise. GI symptoms may be absent or mild. Diarrhoea or steatorrhoea. Abdominal pain diffuse. Weight loss.
Mouth ulcers.
Angular stomitis.
Anaemia/pallor.
Dermatitis herpetiformis.
Subgroups of coeliac disease
CLASSIC - 50%
Typical symptoms
ATYPICAL
Lacks GI symptoms but presents with deficiency state or extra intestinal features
SILENT - 20%
No signs of symptoms
NON-RESPONSIVE
REFRACTORY - 1%
Pathophysiology of coeliac disease.
Proteins in wheat, barley, rye are broken down by tissue transglutaminase into GLIADIN.
Gliadin then presents to T cells via HLA class 2 DQ2 and DQ8.
T cells produce inflammatory cytokines.
Over expression of IL 15
47.
Investigations for coeliac disease
IgA anti-tissue transglutaminase antibodies - highly specific and sensitive. They become undetectable after 6 months of a gluten free diet.
FBC - microcytic anaemia from iron deficiency
Howell-Jollie bodies (leukocytes).
LFTs - raised transaminases.
Small bowel biopsy is gold standard - need to still be consuming gluten.
Treatment of coeliac disease
GLUTEN FREE DIET!
NHS can subsidise gluten free products.
Recommended to have 5 yearly pneumococcal vaccinations.
Hernias - most to least common
Inguinal (indirect or direct).
Femoral.
Umbilical and para-umbilical.
Incisional.
Ventral and epigastric.
Types of hernias: reducible/irreducible/strangulation.
Reducible:
- Lump disappears lying down, not painful.
- Cough impulse.
Irreducible:
- Adhesions to sac wall mass larger than neck not reducible.
- Cough impulse.
Strangulation:
Contents restricted by neck so circulation is cut off - gangrene inevitable.
- Severe pain, central, colicky.
- Vomiting, distension, constipation (from obstruction).
- Tender, tense.
- No cough impulse.
- Noisy bowel sounds.
Hernias most likely to strangulate
- Femoral
- Indirect inguinal
- Umbilical
Indirect inguinal hernia
Pass through internal ring.
Lateral to inferior epigastric vessels.
May be congenital.
Can be controlled by pressure over internal ring.
Commonly strangulates due to narrow neck.
Often extends to scrotum.
Does not readily reduce on lying.
Hernia does not reach full size until the patient has been up for some time, does not reduce on lying
Direct inguinal hernia
Pass through posterior wall of inguinal canal
MEDIAL to inferior epigastric vessels
Always acquired
Not controlled by pressure over internal ring
Rarely strangulate due to wide neck
Reduces spontaneous on lying
Borders of the inguinal canal
Anterior - skin, external oblique aponeurosis
Posterior - conjoint tendon forms posterior well medially, transversalis fascia laterally
Above - internal oblique and transversus abdominis
Below - inguinal ligament
Describe a femoral hernia (anatomy, epidemiology)
Anatomy:
- Passes through the femoral canal.
- Medial to the femoral sheath.
- Femoral sheath contains the femoral artery and vein.
Epidemiology:
- Females > Males.
- More common in the middle aged and elderly.
- Swelling BELOW and LATERAL to pubic tubercle.
- Enlarges on standing and coughing.
- DIsappears on lying down.
Strangulation common due to narrow neck.
Exomphalos
Rare condition.
Failure of all or part of midgut to return to abdominal cavity in foetal life.
Presentation of congenital diaphragmatic hernias.
Different types.
In more serious cases, presents as respiratory distress shortly after birth and require urgent surgery.
Other examples: large oesophageal hiatus which present with regurgitation, vomiting, dysphagia and progressive weight loss in the child.
List the types of acquired hiatus hernias.
Sliding (80%)
- Stomach (GO junction and cardia sometimes) slides through diaphragmatic hiatus.
- It is covered anteriorly with peritoneal sac, posteriorly with extraperitoneum.
- It disturbs cardio-oesophageal mechanism.
Rolling (20%)
- Cardia remains in position.
- Gastric fundus moves up and lies alongside the GOJ, which creates a bubble of stomach in the thorax.
- This is a true hernia within a peritoneal sac.
- No regurgitation symptoms.
- Represents progressive weakening of hiatus muscles.
- 4x more common in females.
- Occurs in obese, middle aged and elderly.
Presentation of acquired hiatus hernia.
Cough. Dyspnoea. Palpitations. Hiccoughs. Retrosternal burning. Pain worse on lying and swooping.
Occult bleeding from oesophagitis.
Treatment of hiatus hernias.
Treat symptomatically.
If unsuccessful, laparoscopic repair indicated.
Epidemiology of colon cancer.
Epidemiology:
- 50 per 100,000.
- 3rd most common malignancy.
- Risk increases with age.
- Males > Females.
- FHx (HNPCC, FAP)
Risk factors of colon cancer.
Risk Factors:
- UC or Crohn’s
- Pelvic radiotherapy
- Smoking
- Alcohol
- Obesity
- Sedentary lifestyle
- Red meat
- DMII
- Aspirin/NSAIDs
- Cholecystectomy
- Low fibre diet
Gram-negative, oxidase positive, non-lactose fermenting bacilli.
Pseudomonas aeruginosa.
This bacterium can cause a range of infection such as pneumonia, urinary tract infections and skin infections amongst others.
Gram-negative, maltose-utilising diplococci
Neisseria meningitidis
Which is mostly known for causing meningitis.
Gram-negative, oxidase positive, growth at 42 C, comma-shaped rods
Vibrio cholerae
Which can cause severe rice-water diarrhea in places where water has been contaminated with the organism.
Dehydration and electrolyte imbalance is a common cause of death, and therefore proper hydration is vital to prevent death.
Gram-negative, oxidase positive, catalase positive comma-shaped rods
Helicobacter pylori
Which causes chronic gastritis and peptic ulcer disease.
Gram-positive, urease positive, catalase positive cocci
Staphylococcus epidermidis
Which is part of the normal skin flora but can also be responsible for infection of catheters and other devices such as mechanical heart valves.
Gram-positive, catalase positive cocci
Staphylococcus bacteria
Which can further be differentiated based on the coagulase positivity and novobiocin sensitivity.
Gram-positive aerobic bacilli
Listeria, Bacillus and Corynebacterium bacteria.
Gram-negative, oxidase-positive comma-shaped rods
Campylobacter jejuni which grows at 42 degrees celcius,
Vibrio cholerae which grows in alkalin media
Helicobacter pylori which produces urease.
Gram-negative, maltose-utilising diplococci
Neisseria meningitidis bacteria.
Tumour marker of colonic cancer
Carcinoembryonic antigen (CEA)
Note: Screening for colonic cancer using CEA is not justified!
It is falsely elevated in a number of non-malignant disease states such as cirrhosis and colitis.
Metoclopramide (antiemetic) is contraindicated in which disease?
Parkinson’s disease (PD)
Metoclopramide is a dopamine antagonist which can make the symptoms of PD worse. There is a degeneration of the basal ganglia in PD and a lack of dopamine. Further inhibiting the action of dopamine increases the symptoms of PD.
Carcinoid tumour markers?
Urinary 5-HIAA
Plasma chromogranin A
Causative organism that causes fat malabsorption, therefore greasy stool can occur.
It is resistant to chlorination, hence risk of transfer in swimming pools.
Giardia lamblia
Which bacteria is seen with antibiotic use?
Clostridium difficile
Borders of the femoral canal?
Laterally - Femoral vein
Medially - Lacunar ligament
Anteriorly - Inguinal ligament
Posteriorly - Pectineal ligament
Types of shock
Septic Haemorrhagic Neurogenic Cardiogenic Anaphylactic
Hesselbach’s triangle boundaries?
Note:
Direct hernias pass through Hesselbachs triangle.
Superolaterally - Epigastric vessels
Medially - Lateral edge of rectus muscle
Inferiorly - Inguinal ligament
Most common complication of endoscopic retrograde cholangiopancreatography (ERCP)?
Acute pancreatitis is the most common complication of ERCP
Linitis plastica
Linitis plastica produces a diffuse infiltrating lesion, the stomach is fibrotic and rigid and will not typically distend.
This may be described as a ‘leather bottle stomach’.
Diagnosis is made with a combination of pathology examination with endoscopy, radiological or surgical assessment.
Pathologically signet-ring cell proliferation occurs.
Indirect inguinal
Indirect inguinal hernia is lateral to epigastric vessels
Indirect inguinal hernias occur due to failure of the processus vaginalis to regress.
The protrusion occurs through the deep inguinal ring and enters the inguinal canal.
It may progress and enter the scrotum in males or labia in females.
Sulphasalazine important side effect.
Sulphasalazine can cause oligospermia and infertility in men
Aminosalicylate drugs
5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis
Sulphasalazine
a combination of sulphapyridine (a sulphonamide) and 5-ASA
many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis
other side-effects are common to 5-ASA drugs (see mesalazine)
Mesalazine
a delayed release form of 5-ASA
sulphapyridine side-effects seen in patients taking sulphasalazine are avoided
mesalazine is still however associated with side-effects such as GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis
Olsalazine
two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria
*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine
Metoclopramide
Metoclopramide is a D2 receptor antagonist mainly used in the management of nausea. Other uses include:
gastro-oesophageal reflux disease
prokinetic action is useful in gastroparesis secondary to diabetic neuropathy
often combined with analgesics for the treatment of migraine (migraine attacks result in gastroparesis, slowing the absorption of analgesics)
Adverse effects extrapyramidal effects: oculogyric crisis. This is particularly a problem in children and young adults hyperprolactinaemia tardive dyskinesia parkinsonism
List 2 opioid agonists used as antidiarrhoeal agents.
Loperamide
Diphenoxylate
They act on u-opioid channels in GIT.
Clinical features of colon cancer
Dependent on site of cancer
Left:
- Fresh rectal bleeding
- Early obstruction
- Tenesmus
- Mucus (if rectal)
- Early change in bowel habit
- Mass in LIF
Right:
- Anaemia from occult bleeding
- Altered bowel habit
- Mass in RIF
Colicky pain
Weight loss
Obstruction or perforation
Hepatomegaly/ascites if mets
Peritonitis
Signs of peritonitis
Rock hard abdomen
Rebound tenderness
Absent bowel sounds
Most common places for bowel cancer?
Rectosigmoid 45%
Ascending colon 30%
Descending colon 15%
Transverse colon 10%
Pathophysiology of colon cancer
Malignant transformation of benign adenomatous polyp.
Accumulation of multiple genetic mutations:
- APC gene
- K-ras gene - failure leads to cell proliferation
- DCC gene - has a role in invasion and metastasis
- p533 gene - role in impaired apoptosis and cell proliferation
HNPCC
Hereditary non-polyposis colon carcinoma
Also known as Lynch syndrome
Occurs at a young age with family history
- autosomal dominant
Mean age 45, lifetime risk 80%
It is the most hereditary syndrome
Majority occur proximally
Increased risk of other cancers: endometrium, ovary, urinary tract, stomach, small intestine, pancreas, CNS
Regular colonoscopy every 1-2 years from 25
Criteria for diagnosis - 3+ relatives with colon cancer (1 must be 1st degree, must be across 2 generations) & 1 family member affected under 50, FAP excluded
FAP
Familial adenomatous polyposis
Hereditary disorder causing numerous polyps and resulting in colon carcinoma before 40
Autosomal dominant
Patients usually asymptomatic
Diagnosis by colonoscopy (100+ polylps) and genetic testing (APC gene)
Treated with colectomy
Polyps present in 50% by 15 and 95% by 35
Extra intestinal manifestations:
- osteoma of skull/mandible
- sebaceous cysts
- increase in cancer: small intestine, pancreas, thyroid, brain, liver and gastric cancer
Treatment of colon cancer
Surgery - without metastatic disease.
- Tumour + resection margins + pericolic lymph nodes removed.
- Reanastamose or stoma
Adjuvant therapy =
- If lymph spread it can’t be controlled with surgery alone
Chemotherapy with 5-FU or carbecitabine or irinotecan
Investigations for colon cancer
FBC - anaemia
LFTs - for mets
Colonoscopy for diagnosis + biopsy (GOLD STANDARD)
CT colongraphy
CT or MRI and liver US for staging
PET for recurrent but not initial cancer
CEA is raised in colon cancer but is not useful for screening. Good prognostic factor, better outcome if CEA negative,
Screening for colon cancer
Faecal occult blood
Every 2 years after 60
When to refer for suspected bowel cancer?
> 40 + rectal bleeding + loose stools for over 6 weeks
> 60 with rectal bleeding OR loose stools >6 weeks regardless of other symptoms
If right lower abdominal mass consistent with large bowel
Palpable rectal mass (NOT pelvic - urology or gynae referral)
Men with unexplained iron deficiency anaemia <11
Non-menstruating women with unexplained iron deficiency anaemia <10
Staging for bowel cancer
Dukes A - tumour confined to bowel (10%) B - extension through bowel wall (35%) C - tumour involving lymph nodes (30%) D - distant mets (25%)
Or can use TNM
T - 1 submuscosa, 2 muscularis propria, 3 pericolorectal tissues, 4A surface of visceral peritoneum, 4B directly invades
Symptoms of peritonitis
Abdominal pain ** Localised pain if contained, generalised after rupture Anorexia Nausea Vomiting Fever and chills Diarrhoea
Signs of peritonitis
High fever in early stages
Rebound tenderness
Absent bowel sounds
Rock hard abdomen
Guarding and rigid abdomen
Hypotensive
Signs of septic shock
DRE increases abdominal pain
Aetiology of primary peritonitis
Spontaneous bacterial peritonitis is acute bacterial of infection of ascitgic fluid resulting from translocation ofbacteria across gut wall
Complications of ascites
90% is mono-microbial
40% E.coli, 7% Klebsiella pneumonia, 15% strep 30%
Predominantly gram negative
Aetiology of secondary peritonitis
Pathogens depend on location in GI tract
Mainly gram positive in upper GI tract
Colon perforation generally multi-microbial and predominantly gram negative
All caused by perforation
Causes of peritonitis
Malignancy Penetrating trauma Ulcer perforation Stone perforation Iscahemic bowel Bowel obstruction Crohn's Appendicitis Post-operative Peritoneal dialysis Pancreatitis
Investigations for peritonitis
FBC - raised WBC, CRP
LFTs, amylase and lipase for pancreatitis
Blood cultures - sepsis
Peritoneal fluid for culture
Urinalysis to rule out urinary tract pathology
Abdominal x=ray
CT/MRI
Treatment for peritonitis
Correction of underlying pathology
Systemic antibiotics
Supportive therapy to prevent organ system failure
Antibiotics are dependent on the cause - usually 3rd generation cephalosporin
Haemodynamic, pulmonary and renal support = fluid resuscitation, monitor renal function, blood gases, urine output, BP, HR
Nutrition support - high requirement in sepsis
Surgery to correct pathology
Describe pain coming from fore, mid and hindgut
Foregut = stomach, duodenum, liver, pancreas. Pain described as upper abdominal pain.
Midgut = small bowel, proximal colon and appendix. Pain felt in umbilicus
Hindgut = distal colon and genito-urinary tract. Lower abdominal pain
Causes of diffuse abdominal pain
Pancreatitis Diabetic ketoacidosis Early appendicitis Gastroenteritis Intestinal obstruction Mesenteric ischaemia Peritonitis Sickle cell anaemia crisis Spontaneous bacteria peritonitis Typhoid fever
Red flags for abdominal pain
Severe pain Tachycardia Hypotension Confusion Signs of peritonitis Abdominal distension
Causes of RUQ pain
Appedicitis with gravid uterus Cholecystitis Biliary colic Congestive hepatomegaly Hepatitis Perforated duodenal ulcer
Causes of RLQ pain
Appendicitis
Caecal diverticulitis
Merkel diverticulitis
Mesenteric adenitis
Causes of lower abdominal pain - R or L
Abdominal or psoas abscess Abdominal wall haematoma Cystitis Endometriosis Strangulated hernia IBD PID Renal stone Ruptured AAA Ectopic pregnancy Ovarian cyst torsion
Define diarrhoea
Passage of >200g of stool per day
Can be acute or chronic
Categories of diarrhoea
OSMOTIC
- when unabsorbable water solutes remain in the bowel and retain water
- Stops with fasting
- Examples: sorbitol, malabsorption causing high concentration in lumen, absorptive defect e.g. lactase deficiency
SECRETORY
- Bowel secretes more electrolytes and water
- Persists with fasting
- Causes: infection, malabsorption. drugs (colchicine, quinine), endocrine tumours
- Enterotoxins cause block of Na/H+ exchange or absorption of Cl-
INFLAMMATORY
- reduced surface area or contact time
- Causes: bowel resection, IBD, Coeliac, shigella
Causes of acute diarrhoea
Likely to be infective
bacteria: salmonella, campylobacter, shigella, E.coli, C. Diff. bacillus cereus
viral: norovirus, rotavirus, CMV, hep A
parasite: giardia,
Drugs: antibiotics, cytotoxic drugs, PPIs, NSAIDs
Ask about recent travel abroad
Causes of chronic diarrhoea
IBS IBD Bowel resection Coeliac disease Pancreatic insufficiency Lactose intolerance Colon cancer Lymphoma Hyperthyroidism Diabetes
Red flags for diarrhoea
Blood Pus Fever Signs of dehydration Chronic Weight loss
Management of acute diarrhoea
- Enquire about red flag symptoms
- Assess for dehydration
- Offer Oral rehydration therapy - 100ml per episode. if sever then IV 5% dextrose
- Stool cultures
- Faecal examinati0on for parasites and ova
- Faecal alpha 1 antitrypsin levels - high in entroinvasive infections usually self-limiting
Only requires supportive treatment
Causes of constipation
- lack of fibre or fluid intake
- immobility
- old age
- bowel obstruction: volvulus, adhesions, hernia, faecal impaction, strictures
- IBS
- Drugs: opiates, anti-cholinergic, calcium antagonists, iron supplements, anatacids, antipsychotics, antispasmodics, general anaesthetics
- Colon cancer
- Obstruction: strictures, Crohn’s, pelvic mass
- Metabolic/endocrine: hypothyroid, hypercalcaemia, hypokalaemia
- Neuromuscular: spinal or pelvic nerve injury, diabetic neuropathy
- Parkinsonism
- Diabetes
- Pregnancy
- Depression
Red flags for constipation
Distended abdomen Vomiting Blood in stool Weight loss Severe constipation with recent onset or worsening Over 50
Investigations for constipation
Blood tests
FBC, U&E, TFTs, calcium
Blood glucose
Abdominal X-ray for masses or obstruction
PR exam
Barium enema or colonoscopy/sigmoidoscopy
Rome III criteria for functional constipation
Functional constipation. must include 2 or more of:
- straining
- lumpy/hard stools
- sensation of incomplete evacuation
- Sense of anorectal obstruction
- Manual manoeuvres
- Less than 3 per week
Each symptom must be present >25%
Bristol Stool Chart
- Separate hard lumps
- Lumpy sausage shape
- Like sausage with cracks
- Sausage, smooth and soft
- Soft blobs with clear cut edges
- Fluffy with ragged edges (mushy)
- Watery, no solid pieces
Management of constipation
INITIAL if no alarm
- Patient education
- High fibre diet
- Increase fluids
- Increase exercise
- Bulk laxatives
- Bulk laxatives e.g. ispaghula husk
- Osmotic or stimulant laxatives
- Refer
Symptoms of IBS
6 month history of either: abdominal pain or discomfort, bloating or change in bowel habit
- Pain improves in defaecation
- Altered passage of stool: straining, urgency, incomplete evacuation
- Abdominal bloating
- Distention
- Symptoms aggravated by eating
- Rectal mucus
- lethargy
- Nausea
- Backache
- Urinary frequency and urgency
- Headaches and migraine
Epidemiology of IBS
10-20% of population
Increased in women (2:1)
Peak between 20-40
RF
Emotional stress
Food poisoning or gastroenteritis
Mental health condition
Criteria for IBS
Rome III Criteria
Recurrent abdominal pain for over 3 months, at least 3 days per month, PLUS 2 or more of:
- Pain improves with defaecation
- Change in stool frequency
- Change in stool form
Pathophysiology of IBS
Psychological factors, altered GI motility, altered visceral sensation
7-30% develop IBS following gastroenteritis
Investigations for IBS
FBC, ESR, CRP Coeliac screen CA-125 if ?ovarian cancer Faecal calprotectin if ?IBD Colonoscopy or sigmoidoscopy Refer if any RED FLAGS
Classification for IBS
IBS-C - constipation - loose stool <25%, Hard stools >25%
IBS-M - mixed - both hard and soft stools >25% of the time
IBS-D - diarrheoa - loose stool >25%, hard <25%
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Treatment of IBS
Constipation
- high fibre diet, bulk forming laxatives (ispaghula husk) or osmotic (but avoid lactulose)
Diarrhoea
- reduce fibre + loperamide, codeine, colestyramine
Pain and bloating - use spasmolytic drugs e.g. amitryptiline
Treat the symptoms of the patient
CBT, hypnotherapy, psychotherapy
Symptoms of achalasia
Dysphagia Affecting solids more than liquids Regurgitation in 80% Chest pain in 50% - occurs after eating, retrosternal Heartburn is common Weight loss suggests malignancy Nocturnal cough No signs!
Pathophysiology of achalasia
Smooth muscle layer of oesophagus has impaired peristalsis and failure of the sphincter to relac causes functional stenosis or stricture
Most have no underlying cause
Investigations for achalasia
CXR - vastly dilated oesophagus
Barium swallow - usually precedes endoscopy when investigating dysphagia as can perforate malignancy with endoscope.
Birds beak - narrow segment in distal oesophagus.
Endoscopy
Manometry - is GOLD STANDARD - can detect 90% of cases. High resting pressure in cardiac sphincter, incomplete relaxation on swallowing and absent peristalsis
If no radiological evidence - it may be pseudoachalasia
Management of achalasia
Calcium channel blockers and nitrates - reduce pressure in lower sphincter. Only works in 10%
Heller myotomy - divide muscles longitudinally (90% success)
Pneumatic dilation - balloon inflated to rupture muscle, leaving mucosa intact
Enodscopic injection of botulinum but recurs in the majority.
Endoscopic stent insertion
Causes of dysphagia
Benign stricture: schataki ring, GORD Malignant stricture: SCC, adenocarcinoma Stroke Achalaisa Parkinson's Motor neurone disease Myasthenia gravis
Epidemiology of oesophageal cancer
13th most common in the UK, 8th most common worldwide
Increased in age - most are over 60
Increased in men
High in East African and Asia
Increasing prevalence of adenocarcinoma, decreasing SCC
RF Adenocarcinoma: - Caucasian - Barrett's oesophagus - Obesity
SCC:
- Achalasia
- Corrosive strictures
- Coeliac
- African
Both
- Smoking
- Alcohol
- Radiation to area
- Genetics
- Diet (high sat fat)
Symptoms of oesophageal cancer
Dysphagia (initially liquids then solids) Vomiting Anorexia Weight loss Blood loss/ melaena Odynophagia (painful swallowing) Hoarseness Retrosternal or epigastric pain Persistent cough Lymphadenopathy
Types of oesophageal cancer
Adenocarcinoma - more common in lower oesophagus. Mainly progression from Barrett’s oesophagus
Squamous cell carcinoma - can be anywhere along the oesophagus
Investigations for oesophageal cancer
FBC - anaemia
U&Es, LFTs for baseline
CRP - can be raised
Glucose
Urgent endoscopy and biopsy
CXR for mets and spread
Double contrast barium swallow
Staging - FDG PET/CT or MRI
Endoscopic Ultrasound
Prognosis of oesophageal cancer
50% have mets at diagnosis
presents late as 75% of lumen needs to affected around the circumference before difficulties present
20-25% 5 year survival rate
AC and SCC have the same prognosis
Management of oesophageal cancer
Primary = surgery +/- chemo +/- radiotherapy
Surgery
- antibiotic and antithrombotic prophylaxis given
- If early, endoscopic muscosal resection
- If late: oesophagectomy endoscopically if possible
- Abdominal lymphadenectomy is beneficial
- Chemo and radiotherapy shrink tumour prior to resection
Palliative
- Can use chemo/radiotherapy to decrease bulk
- Fit stent to allow swallowing
- PEG for feeding
- ANALGESIA
Epidemiology of GORD
25% of adults, 5% have daily symptoms
More common in men
Risk factors of GORD
- Obesity
- Pregnancy
- Systemic sclerosis
- Drugs: nitrates, TCAs, anticholinergics, calcium channel blockers
- Hiatus hernia
- Increased intra abdominal pressure
- Smoking
- Alcohol
- Large meals
Symptoms of GORD
Heartburn worsened on lying or bending down Retrosternal discomfort Regurgitation Pain on swallowing Nocturnal cough Excessive salivation Chronic hoarseness Acid brash Pain relieved by antacids
No signs
Endoscopic findings in GORD
60-70% have normal endoscopy (non-erosive reflux disease)
20-30% erosive oesophagitis
6-10% Barrett’s oesophagus
Can show basal hyperplasia, inflammation, Goblet cell metaplasia, thinning of squamous layer or dysplasia
Pathophysiology of GORD
Spectrum of disorders from endoscopy negative GORD to oesophageal damage
3 main causes:
- Poor oesophageal motility
- Dysfunction of lower oesophageal sphincter (permanent or intermittent relaxation or increase in abdominal pressure)
- Delayed gastric emptying
Investigations for GORD
FBC to exclude anaemia
H.pylori stool test (stool antigen test)
Endoscopy +/- biopsy (must be drug free for 2 weeks)
Barium swallow
Management of GORD
Assess for possibility of GI bleed
Simple lifestyle advice: healthy eating, weight reduction, smoking cessation.
Avoid precipitants: smoking, alcohol, coffee, chocolate, fatty foods, acidic foods e.g. tomatoes, oranges
Raised head of bed
Avoid eating late at night
If H.pylori positive, treat
Full dose PPI for 4 weeks.
Can offer H2 receptor agonist therapy as alternative.
Antacids as required
If very severe and uncontrollable, can fit magnetic band around LOS to aid closure.
Urgent referral criteria for GORD
Dysphagia
Dyspepsia + weight loss/anaemia
Dyspepsia new onset in over 55s
Dyspepsia plus one of:
- FHx of upper GI cancer
- Barrett’s
- Pernicious anaemia
- upper abdominal mass
- known dysplasia
Complications of GORD
Oesophagitis Ulceration Anaemia Stricture Barrett's oesophagus
What is Barrett’s oesophagus
Premalignant condition
Normal squamous lining is replaced by columnar cells
Adaptive response to GORD
Classification of GORD
Savary-Miller Grading system
- single or multiple erosions on single fold
- multiple on multiple folds
- multiple circumferential erosions
- ulcers, stenosis or oesophageal shortening
- Barrett’s
Can use Los Angeles Grades A-D
Epidemiology of peptic ulcer disease
Of the 1% with reflux receiving endoscopy, 13% will have peptic ulcer disease
1 per 1000 (0.1%)
Decreasing in Western populations
Increased in males
RFs
- Smoking
- Alcohol
- NSAID or steroid use
Symptoms of peptic ulcer disease
Post-prandial epigastric pain Relieved by food Nausea Oral flatulence Bloating Intolerance of fatty foods Heartburn Pain can radiate to the back if ulcer is posterior Fatigue or dyspnoea if anaemia melena
Signs
Epigastric tenderness
Aetiology of peptic ulcers
H. pylori Bile acids NSAIDs Steroids pepsin Stress Smoking Changes in mucus consistency Alcohol
Pathophysiology of H.pylori
Gram negative spiral
Lives deep beneath mucus layer
Closely adheres to epithelial surface
Uses an adhesin (BabA)
Any acidity is buffered by urease
Pathophysiology of peptic ulcers
- Depletion of somatostatin
- Increase gastrin release from G cells
- Increased acid secretion
- Increased acid load in duodenum will cause metaplasia
Investigations for peptic ulcer disease
FBC - iron deficiency anaemia
H. pylori test - 13C breath test or stool antigen test
Endoscopy if there are any warning signs
Complications of peptic ulcers
Perforation (more common in duodenal)
Gastric outlet obstruction
Bleeding
Anaemia
Treatment of H. pylori
TRIPLE therapy for 7 days
Clarithromycin
PPI
Amoxicillin or metronidazole
Treatment of peptic ulcers
Lifestyle advice: stop smoking and alcohol
If H.pylori positive treat
If taking NSAIDs = STOP
If neither is positive (rare), endoscopy for ? Zollinger-Ellison syndrome
Endoscopic ablation if actively bleeding
Functional dyspepsia
Chronic discomfort in the upper abdomen without any organic disease (as seen in GORD)
Drug treatment not useful.
Prokinetic drugs e.g. metoclopramide may be helpful
Define cholelithiasis
Cholelithiasis: formation of gallstones within the gallbladder
Define choledolithiasis
Choledocholithiasis: stones in the common bile duct
Epidemiology of gallstones
10-15% of Western population but only 10-25% of these become symptomatic
Increases with age
Increased in women
increased in middle age
Fair, fat, fertile, female and 40
RF FHx Obesity Pregnancy Sudden weight loss Haemolysis (sickle cell) Loss of bile salts (ileal resection) Drugs (oestrogens, fibrates, somatostatin) Diabetes Oral contraception Crohn's
Symptoms of gallstones
70% are asymptomatic
Pain in RUQ or epigastrium, can radiate to the back
Pain begins post-prandially
Pain is intense and dull
Subsides spontaneously, after analgesia, vomiting, antacids, defaecation, flatus or positional changes
Sporadic and unpredictable episodes
Persists from 5 minutes to 24 hours
Nausea or vomiting can accompany pain
Intolerances to fats
Abdominal distension
Can have diaphoresis (excessive sweating)
Signs of gallstones
No findings if asymptomatic
Tachycardia (due to pain)
No peritoneal signs
If complications: can have jaundice, positive Murphy’s sign or pancreatitis
Types of gallstones
Cholesterol stones (80%)
Large, solitary and radiolucent
Increased with increased cholesterol
Pigment stones (20%)
Small, black and friable, irregular radiolucent
RFs - haemolysis and cirrhosis
Occurs with high levels of unconjugated bilirubin
Calcium bilirubinate can crystalise to form stones
Mixed stones - calcium salts, pigment and cholesterol, 10% are radio-opaque
Brown pigment stones <5%, due to stasis and generally present with E.coli or Klebsiella infection
4 stages of gallstone formation
- Lithogenic state in which conditions favour gall stones: high cholesterol, low bile sales
- Asymptomatic gallstones
- Symptomatic gallstones with episodes of biliary colic
- Complicated cholethiasis
Investigations for gallstones
Blood tests: FBC, LFTs, amylase and lipase
If uncomplicated or simple biliary colic, will be normal
Abdominal x-ray to rule out obstruction
US - best way to see stones. They are usually echogenic, mobile and cast an acoustic shadow.
ERCP - can be used to see and remove stones in CBD
MRCP - using MRI, reserved for suspected choledolithiasis.
Management for gallstones
Manage with pain with morphine
Laparoscopic cholecystectomy
If unfit for surgery can surgical drain the gallbladder (cholecystotomy)
If stones in bile duct then - cholecystectomy and CBD exploration and stone extraction
Consider mechanical or shock wave lithotripsy
If asymptomatic watch and wait.
Reasons for cholecystectomy in asymptomatic patients
Stone > 2cm
High risk of GB carcinoma
Non-functioning GB
Sensory neuropathy of abdomen
Sickle cell anaemia
Cirrhosis or portal hypertension
Children
Transplant candidates
Diabetics
Complications of gallstones
Cholangitis if in biliary tree
GB empyema
Gallstone ileus
Fibrosis of gallbladder
Loss of gallbladder function
GB carcinoma
Epidemiology of cholecystitis
10% have gallstones 1/3 get cholecystitis Increases with age increased in females Although acalculus is more common in men
RFs Gallstones Trauma Obesity Rapid weight loss Pregnancy Crohn's Hyperlipidaemia
RF for acalculus Major surgery Long term parenteral nutrition Sepsis Prolonged fasting
Symptoms of cholecystitis
Upper abdominal pain
may radiate to right shoulder or scapula
Pain begins in epigastrium and localises to RUQ
Starts colicky but becomes constant in all cases nausea and vomiting
Fever
Signs of cholecystitis
Raised WCC
Positive Murphy’s sign
Local peritonism
Fever
Tenderness in epigastrium/RUQ
Tachycardia
Jaundice
Guarding/rebound tenderness palpable GB
Pathophysiology of cholecystitis
90% are calculous
- Stone obstructs cystic duct causing distension of GB
- Blood flow and lymph drainage of the gallbladder are compromise and can cause ischaemia and necrosis
Acalculous 10%
- Cause unclear.
- If fasting GB has no CKK stimulus and so bile remains stagnant
Causes of cholecystitis
GALLSTONES
Acalculus MI Sickle cell Salmonella Diabetes AIDS CMV pregnancy
Investigations for cholecystitis
Blood tests -
Raised WCC
Raised ALT and AST
Check amylase and lipase for pancreatitis
Urinalysis to rule out pyelonephritis and renal stones
Pregnancy test
CXR to rule out lower lobe pneumonia or see radiopaque stones
US - thickened gall bladder wall >3mm, pericholecystic fluid or air on GB or GB wall
CT with IV contrast
Treatment for cholecystitis
Rest IV hydration Bowel rest - no intake Correct electrolyte imbalance Analgesia IV antibiotics (tazocin/metronidazole) Laparoscopic cholecystectomy ERCP
Triad of ascending cholangitis
Charcot’s triad
RUQ pain
Jaundice
Fever
Reynold’s pentad adds confusion and hypotension
Cholangitis
Infection of biliary tract
Majority of cases are due to gall stones
10-30% are due to benign strictures, post-op damage, tumours, bacteria (anaerobes) and parasites
Carries significant risk of death due to shock or multi organ failure
Blood test results in cholangitis
Raised CRP or WCC Increased LFTs (ALP, AST, ALT, GGT)
Epidemiology of gastric cancer
8th most common cancer
Increases in Asia and South America
Increases with age
More common in men
50% in pylorus, 25% in lesser curve, 10% cardia, 2-8% lymphomas
Pathophysiology of gastric cancer
Correa’s cascade
- Chronic non-atrophic gastritis
- Atrophic gastritis
- Intestinal metaplasia
- Dysplasia
- Cancer
Can spread to ovaries
2 main types:
- Intestinal (type 1) with well formed glandular structures. Ulcerating lesions with heaped rolled edges. Strong environmental association
- Diffuse (type 2) poorly cohesive cells. Poorer prognosis. Loss of expression of E=cadherin molecule
Investigations for gastric cancer
FBC for anaemia
LFTs
Rapid access flexible endoscopy: Gastroscopy and biopsy
Endoscopic US for local staging and depth
Chest/Abdo/Pelvis CT
18F PET/CT
Management of gastric cancer
Surgery is treatment of choice
- If distal then subtotal gastrectomy, if proximal then total
- If curable remove D2 lymph nodes
Perioperative chemotherapy is standard with 5-FU, but can be palliative
Blood transfusion if anaemia
Corticosteroids for management of anorexia
Prognosis of gastric cancer
Overall survival rate 15%
11% live 10 years
Younger patients have a better prognosis
Poorer prognosis if paraneoplastic syndrome
Risk factors of gastric cancer
H.pylori infection Smoking Diet: rich in pickles, salt, smoked meats and fish FHx Poor socioeconomic status Previous gastric surgery Obesity
Epidemiology of pancreatitis
150 per million
3% of all abdominal pain in hospital
High in USA & Scandinavia
Equal gender distribution
Risk factors of pancreatitis
- Alcohol abuse
- Some family history (alpha 1 antitrypsin deficiency)
- Hyperlipidaemia
- Gallstones
- CF
- Smoking
- Oestrogens
- Hypothermia
- Congenital abnormalities
- Vasculitis
Symptoms of acute pancreatitis
Severe upper abdominal pain
Decreases steadily over 72 hours
Pain focused in LUQ or epigastrium
Penetrates to the back
Sudden onset vomiting
Signs of acute pancretitis
Mild pyrexia (common), rare but can have hypothermia Hyperlipidaemia Tachycardia Jaundice Abdominal tenderness and rigidity Bowel sounds in early phase Paralytic ileus causes absent bowel sounds Hypoxaemia
In severe: Gross hypotension Pyrexia Tachypnoea Ascites Pleural effusion Body wall staining around umbilicus (Cullens sign) or Grey Turner's (flanks)
Cullen’s sign
Body wall staining around the umbilicus
Grey Turner’s sign
Body wall staining on the flanks
Aetiology of acute pancreatitis
90% are caused by gallstones, alcohol, post-ERCP or idiopathic
Idiopathic Gallstones Ethanol Trauma Steroids Mumps/malignancy Autoimmune Scorpion bite Hyperlipidaemia ERCP Drugs
Viral causes - Coxsackie B, hepatitis, mumps
Drugs - thiazides, valproate, azathioprine
IBD
Alpha 1 antitrypsin deficiency
Sclerosing cholangitis
Vasculitis
Hyperparathyroidism
Pathophysiology of acute pancreatitis
Occurs as a consequence of premature activation of zymogens releasing proteases that digests surrounding tissues.
Severity is dependent on balance between proteases and anti-proteolytic factors (alpha anti-trypsin)
Occurs due to one of:
- Defective intracellular transport and secretion of pancreatic zymogens
- Pancreatic duct obstruction
- Hyperstimulation of pancreas (alcohol/fat)
- Reflex of infected contents into CBD
Investigations for acute pancreatitis
Serum lipase: double the upper limit of normal values
FBC: Leucocytosis
Electrolytes and renal function:
- Elevated creatinine
- High anion gap
- Hypocalcaemia is common
Abdominal XR:
- Rule out perforation and obstruction
Abdominal ultrasound:
- Determines possible cause, such as gallstones
Abdominal CT:
- Stage severity of the pancreatitis
- Pancreatic necrosis
- Pseudocyst
Treatment of acute pancreatitis
- Analgesia,
- IV fluids,
- O2,
- Urinary catheter,
- Naso-jejunal feeding (to avoid pancreatic stimulation),
- Consider CVP monitoring,
- ERCP if gallstone obstructing bile duct
Complications of acute pancreatitis
Pancreatic necrosis (if infected then 3x mortality) - confirmed by CT.
Infected necrosis - fatal without intervention (Infection in 30-70% of necrosis) - IV antibiotics and agrressive surgical debridemnt
Fluid collections
Pancreatic abscess - occurs several months after the attack, requires surgery
Acute pseudo-cyst - occurs 4 weeks after the attack. Can rupture/haemorrhage, requires surgery
Pancreatic ascites from collapsed pseudocyst
Acute cholecystitis
Systemic complications - pulmonary oedema, pleural effusions, consolidation, hypovolaemia, shock, renal dysfunction, hypocalcaemia, hypomagnesaemia, hyperglycaemia, GI haemorrhage, Weber-Christian disease
Prognosis of acute pancreatitis
80% have mild and recover without complications
5% mortality in mild
30% mortality in severe
Classification of acute pancreatitis
Glasgow Prognostic Score
Ranson’s criteria (very similar)
3+ = severe pancreatitis
Can also use APACHE II = 8 or more is severe
Causes of raised amylase
Pancreatitis Renal failure Ectopic pregnancy Diabetic ketoacidosis Perforated duodenal ulcers Mesenteric ischaemia
Pathophysiology of chronic pancreatitis
Long-term pathological process of pancreatic fibrosis + calcification
- Obstruction OR reduction of bicarbonate excretion
- These lead to the activation of pancreatic enzymes, causing pancreatic necrosis
Alcohol causes proteins to precipitate in pancreatic ducts leading to pancreatic dilation and fibrosis.
- Leads to ductal plugging and obstruction
- Increased protein secretion, decreases fluid, decreased bicarbonate production
LARGE DUCT subtype:
- Dilation and dysfunction of large ducts visible on imaging.
- Occurs more in men, steatorrhoea common, requires surgery to alleviate symptoms.
SMALL DUCT subtype:
- Occurs more in women, no diffuse pancreatic calcification.
- Imaging normal - hard to diagnose.
- Patients respond to pancreatic enzyme replacement.
Risk factors for chronic pancreatitis
Risk factors:
- Chronic alcohol use
- Smoking
- Genetics (PRSS1, CFTR, SPINK1)
- Male
- Black
Symptoms of chronic pancreatitis
- Chronic abdominal pain relieved by opiates,
- Steatorrhoea
- Abdominal pain
- Epigastric and radiating to the back
- Nausea and vomiting
- Decreased appetite
- Weight loss
- Steatorrhoea
Signs of chronic pancreatitis
Exocrine dysfunction:
- Malabsorption
- Diarrhoea/steatorrhoea
- Protein deficiency
Endocrine dysfunction:
- Diabetes mellitus
Abdominal tenderness
Hereditary pancreatitis
Rare
Similar to chronic pancreatitis.
Pathophysiology:
- Genetic mutation in PRSS1.
- This increases autoactivation of chymotrypsin C
Clinical features:
- Presents at a young age with epigastric pain
- Exocrine and endocrine dysfunction
High incidence of pancreatic carcinoma
Tropical chronic pancreatitis
Developing countries
Associated with type 1 diabetes
Associated with CFTR and SPINK1 genes
Similar to alcoholic pancreatitis presentation
Autoimmune chronic pancreatitis
High prevalence in Japan
Elevated IgG and serum gammaglobulins
Autoantibodies may be increased
Steroid responsive.
Reversible
Investigations for chronic pancreatitis
- Serum amylase (may be normal)
- US first line then CT -> ERCP: see pancreatic calcification
- Pancreatic function tests: endocrine/exocrine insufficiency
- Blood tests: FBC, U&Es, LFTs, Calcium (hypocalcaemia), Amylase (raised), Glucose and HbA1c
- Secretin stimulation test: positive if pancreatic exocrine function damaged
- Seen in malabsorption: faecal elastase, serum trypsinogen, urinary D-xylose
Tests of pancreatic function:
- GOLD standard is collection of pure pancreatic juice after secretin injection (invasive)
- Pancreolauryl test or PABA test
- Faecal pancreatic elastase
Treatment of chronic pancreatitis
Supportive measures:
- Lifestyle advice - smoking cessation, alcohol abstinence
- Analgesia (may require coeliac plexus block)
- ERCP may reduce pain
- Malabsorption is treated by pancreatic enzyme replacement - Lipase treatment of choice
Octreotide (somatostatin analogue) inhibits pancreatic enzyme secretion and CCK levels
Surgery - pseudocyst decompression, ERCP + lithotripsy
- If large duct dilation: pancreaticojejunostomy
- Pancreatoduodenectomy
Complications of chronic pancreatitis
- Cobalamin deficiency (B12)
- Diabetes
- Pericardial, peritoneal and pleural effusions
- Pseudocysts
- Pancreatic carcinoma
- Increased risk of morbidity and mortality
- 1/3 die in 10 years
Epidemiology of hepatitis A
Very common in developing countries, particularly in early life
Most common viral hepatitis
High risk: India, Africa, South and Central America, Middle Esat
RFs
Risk factors of hepatitis A
- Personal contact
- Occupation: residential home staff, sewage worker
- Travel to high risk areas
Hep A virus
- Small unenveloped RNA virus
- Enterovirus in picornaviridae family
- Incubation period 2-6 weeks
- Spread through faecal oral route
- Can be vaccinated against
Symptoms of Hep A infection
More severe in older patients, children can be asymptomatic
- Mild-flu like symptoms
- Anorexia, nausea, fatigue, malaise, joint pain, mild headache
- Following this: jaundice
- Icteric phase: dark urine, pale stools, jaundice, abdominal pain, pruritus, arthralgia, skin rash
Pathophysiology of hepatitis A
- Receptor binding
- RNA uncoating
- Tranlocation and proteolytic processing. Host ribosomes bind to form polysomes
- RNA replication. Genome copied by viral RNA polymerase
- Virion assembly
- maturation and release.
Shed via biliary tree into faeces
Shedding greatest between 14-21 days after infection
Investigations of Hep A infection
Specific antibody tests - IgM antibody to Hep A (positive for 3-6 months)
IgG occurs after and persists for many years
LFTs - ALT>AST. Raised ALP
Levels return to normal over several weeks
Raised bilirubin
Modest decrease in albumin
Mild lymphocytosis common
Investigations for Hepatitis A infection
Specific antibody tests:
- IgM antibody to Hep A (positive for 3-6 months)
- IgG occurs after and persists for many years
LFTs:
- ALT > AST
- Raised ALP
- Levels return to normal over several weeks
- Raised bilirubin
- Modest decrease in albumin
Mild lymphocytosis common
Treatment of hepatitis A infection
Mainly supportive - fluids, antiemetics, rest
Avoid alcohol until liver enzymes return to normal
For immediate protection can give immune serum globulin
Prognosis of hepatitis A infection
- Excellent
- Self limiting
- No long term sequelae
- No carrier state
- No chronic liver disease
Complications of hepatitis A
- Cholestatic hepatitis,
- Autoimmune hepatitis,
- Relapsing hepatitis A infection 4-15 weeks after first illness
Hep B antibodies
HBsAg:
- Hep B surface antigen
- Indicator of active infection
- If present after 6 months then chronic infection
HBcAg:
- Hep B core antigen
- Detected by its antibody IgM then IgG
HBeAg:
- Hep B e antigen
- Indicator of viral replication
Chronic infection:
- HbsAg and anti-HBcAg (IgG)
Investigation for Hep B infection
Blood tests:
- HBsAg: only detected in first 3-5 weeks after infection, unless chronic infection
- HBsAg antibodies: in vaccinated people
- HBeAg: if positive, active infection
- HBcAg antibodies: past infection
- FBC, bilirubin, LFTs, clotting, ferritin, lipid profile, ceruloplasmin
- Test for Hep C and HIV
- Alpha fetoprotein and liver US for hepatocellular carcinoma screen
Hep B virus
Hep B virus:
- Double stranded DNA
- Hepadnaviridae family
- Incubation period 40-160 days (average 60-90)
- Can be e antigen positive or negative (positive = increase rate of replication)
- Transmission: vaginal or anal intercourse, blood to blood contact, vertical transmission
Epidemiology of Hep B infection
- High prevalence in sub-Saharan Africa, most of Asian and Pacific Islands
- 1 in 350 in UK
- Starting to decline due to vaccinations
Risk factors of Hep B
- Homosexual males
- Sex workers
- IV drug users
- HIV + patients
- Sexual assault victims
- Healthcare workers/needlestick injuries
Management of Hep B infection
- Avoid unprotected intercourse
- Notify HPA
- Supportive treatment - fluids, antiemetics, rest
- Avoid alcohol
- Stop unnecessary medications
Give antiviral agents if:
- Fulminant hepatitis
- HBeAg positive
- Pregnancy with high HBV DNA
Give: peginterferon alpha-21 or tenofovir
- Monitor ALT every 24 weeks, more often if cirrhosis
- Test for HCC (US and alpha fetoprotein)
Can give hepatitis B immunoglobulin to baby to reduce risk of vertical transmission or just after infection to decrease risk
Prognosis of Hep B infection
Cirrhosis 20%
Faster progression in Hep C or HIV positive as well
Signs of symptoms of Hep B infection
Flu like illness: nausea, anorexia, malaise, ache in RUQ
- Jaundice
- Disinclination to drink alcohol
- Dark urine
- Pale stool
- Fever
- In decompensated: ascites, encephalopathy, Gi haemorrhage
Clinical features of Hep C infection
Acute:
- Asymptomatic,
- Often diagnosed on routine blood testing
20-30% get jaundice
Chronic:
- Malaise, weakness, anorexia, abdominal pain
- Symptoms are worse with increased alcohol intake
Epidemiology of Hep C infection
Large number undiagnosed
214,000 in UK
Risk factors of Hep C
- Drug misuse
- Blood transfusion pre-1991
- Sexual intercourse
- Infected pregnant mother
- Healthcare worker
- Needlestick injury
- Tattoo, body piercing
- Sharing razors/toothbrushes
Hep C virus
- Enveloped RNA virus
- Flaviviridae family
- Incubation period 6-9 weeks
- Hep C RNA can be found after 2-4 weeks, antibodies at 6-12 weeks
Transmission: parenteral, bloodborne, sexual contact, vertical transmission
6 genotypes
- 1 = most common
- 2, 3, 4, 5, 6
Investigations for Hep C infection
- Anti HCV serology
- HCV RNA quantitative PCR
- HCV antibody positive for life regardless of treatment
- US: focal lesions, splenomegaly, cirrhosis
- Liver biopsy to assess severity
- Measures of severity: macroglobulin, haptoglobin, apolipoprotein A1, GGT, total bilirubin, transient elastography
- Test for Hep B and HIV
Treatment of Hep C infection
Advice:
- Counselling,
- Barrier contraception,
- Alcohol abstinence,
- Implications of being positive
Drugs effectiveness is related to genotype:
- Better response in type 2 and 3
- Weekly subcut peginterferon alpha2a
Prognosis of Hep C infection
- 50-85% become chronic carriers
- 15% will clear virus completely
- Cirrhosis in 20-30% of chronic
- 1-4% get HCC, 2-5% get liver failure
Co-infection with Hep B or HIV = worse prognosis
Type 1 more likely to clear spontaneously
Hep D virus
- Single stranded RNA virus
- Enveloped spherical deltavirus
- Requires presence of Hep B to replicate
- Patients must be HBsAg positive
- Delta virus
- Bloodborne
- Clinically indistinguishable from Hep B infection
- Replicated only in liver cells
- Increases risk of fulminant hepatic failure, chronic liver disease, cirrhosis and HCC with B+D
Chronic in 30-50%
Incubation 3-20 weeks
Hep E virus
- Hepeviridae
- Non-enveloped single stranded RNA
- Spread via faecal oral route
- Self-limiting with no chronic infections
- Incubation 2-9 weeks
- Fulminant disease in 10%
- Mild flu like symptoms
Define acute liver failure
Occurs when liver loses the ability to regenerate or repair so that decompensation occurs.
Characterised by:
- Hepatic encephalopathy
- Abnormal bleeding
- Ascites
- Jaundice
Fulminant hepatic failure: when failure takes place within 8 weeks of the onset of underlying illness
Late onset/subacute fulminant - when it occurs during 8-26 weeks
Chronic decompensated hepatic failure - after 6 months
Risk factors for acute liver failure
- Chronic alcohol abuse
- Poor nutritional status
- Female
- Chronic Hep B/C infection
- Chronic pain and narcotic use
- Pregnancy
- Paracetamol
- Antidepressant therapy
- Medications
- Illicit drug use
FHx:
- Wilson’s disease,
- Haemochromatosis
Aetiology of acute liver failure
Toxins: alcohol, paracetamol, Reye’s syndrome, drugs (co-amoxiclav, ciprofloxacin, doxycycline, erythromycin), ecstasy, cocaine
Infections: viral hepatitis, EBV, CMV, viral haemorrhagic fevers
Cancer:
- HCC
- Mets
Pregnancy related: acute fatty liver of pregnancy
Autoimmune liver disease
Metabolic:
- Wilson’s disease,
- Alpha 1 antitrypsin deficiency
Vascular:
- Ischaemia or veno-occulsive disease
- Budd-Chiari syndrome
Presentation of acute liver failure
Nausea and vomiting Malaise Abdominal pain RUQ tenderness Drowsiness and possibly confusion Jaundice Abdominal distension - ascites, hepatomegaly Papilledema,, hypertension, bradycardia (from cerebral oedema) Asterixis Palmar erythema Hepatic encephalopathy
Investigations for acute liver failure
FBC:
- Thrombocytopenia,
- Leucocytosis,
- Anaemia
LFTs:
- Very raised transaminases,
- Raised ALP
- Raised INR,
- Raised bilirubin,
- Raised ammonia,
- Low glucose
May have:
- Raised lactate,
- Raised creatinine
Blood cultures:
- Very susceptible to infection
Viral serology
Free copper (Wilson’s),
ABG - metabolic acidosis
Dopper US, CT or MRI
Avoid contrast
Management of acute liver failure
- Intensive care management
- Mannitol to decrease ICP
- Lactulose + neomycin to reduce ammonia
- AKI may require haemodialysis or haemofiltration
- FFP, platelets and anti-fibrinolytic drugs for abnormal bleeding
- Replace glucose as required
Complications of acute liver failure
- Infection: spontaneous peritonitis common
- Cerebral oedema
- Haemorrhage
- Bleeding, sepsis, cerebral oedema, AKI, respiratory failure
Prognosis of acute liver failure
- High morbidity and mortality
- Cause depends on outcome
- Higher survival if Paracetamol, hep A, pregnancy
Define Jaundice
Yellow discolouration caused by accumulation of bilirubin in tissue
Not apparent until serum bilirubin is over 35
It can be pre-hepatic, hepatocellular, post-hepatic
Breakdown of haemoglobin
- Haemoglobin broken down in spleen to biliverdin.
- Biliverdin in plasma converted to unconjugated bilirubin and bound with bilirubin
- Unconjugated becomes conjugated in liver by glucuronic acid
- Secreted into bowels where converted to urobilinogen by bacteria, secreted in stool as stercobilin
Presentation of jaundice
- Any prodromal flu like illness may suggest viral hepatitis
- Pain suggest gallstones
painless suggests cancer - Change in colour of urine and stools
- Pruritus
- Weight loss
- Alcohol or drug use
medication history! amitriptyline, erythromycin, COCP, rifampicin, salicylates
Examination of a patient with jaundice/signs of liver disease
Jaundice - skin and sclera Spider naevi Palmar erythema Gynaecomastia Testicular atrophy Flapping tremor Ascites Splenomegaly Finger clubbing Peripheral oedema
Aetiology of pre-hepatic jaundice
Gilbert’s syndrome - unconjugated hyperbilirubinaemia
Haemolytic anaemia - spherocytosis, pernicious anaemia
Thalassaemia
Trauma
Crigler-Najjar syndrome
Aetiology of hepatic jaundice
Viral hepatitis HCC Alcoholic hepatitis Autoimmune hepatitis Drug induce hepatitis (Paracetamol) Decompensated cirrhosis
Aetiology of post-hepatic jaundice
Gallstones Bile duct strictures Common duct stone Head of pancreas cancer Tumour at ampulla of Vater Pancreatitis GB cancer Primary biliary cirrhosis Primary sclerosing cholangitis
Blood test results in Pre-hepatic jaundice
Raised unconjugated bilirubin
Normal AST, ALP, GGT
Raised reticulocytes
Normal INR, PT
Blood test results in hepatic jaundice
Raised bilirubin ** Raised AST ALT>AST Raised ALP Raised GGT Raised INR and PT Raised urobilinogen with raised or normal bilirubin
Blood test results in Post-hepatic jaundice
Very high bilirubin Raised AST ** Raised ALP ** Raised GGT Raised INR and PT ALT>AST Raised urine bilirubin
Investigations for jaundice
FBC - reticulocytes and blood smear LFTs Hepatitis viral serology Serum ANA and anti-smooth muscle antibody for primary biliary cirrhosis Ferritin for ?haemochromatosis Alpha 1 antitrypsin levels Abdominal US MRI/MRCP Liver biopsy
What is anti-mitochondrial antibody seen in?
Primary biliary cirrhosis
What is anti-nuclear and anti-smooth muscle and microsomal antibody seen in?
Autoimmune hepatitis
What is alpha fetoprotein an indicator of?
Hepatocellular carcinoma
Tests for haemochromatosis
Serum iron
Transferrin
Ferritin
Tests for Wilson’s disease
Serum and urine copper
Serum ceruloplasmin
Antibody positive in Primary Sclerosing
Cholangitis
Antinuclear cytoplasmic antibody
Epidemiology of alcoholic liver disease
Growing incidence
More common in males
Increases with age
RFs
Alcohol consumption - prolonged and heavy
Hep C infection
Female - more rapid progression, requires lower dose of alcohol to achieve
Smoking
Obesity
Over 65
Hispanic
Genetic predisposition - alcohol metabolising enzymes
Pathophysiology of alcoholic liver disease
3 stages: steatosis (fatty liver) –> alcoholic hepatitis –> alcoholic liver cirrhosis
Alcohol converted to acetaldehyde by alcohol dehydrogenase. At thee same time NAD converted to NADH
NADH inhibits gluconeogenesis and increases fatty acid oxidation
Uses other pathways to metabolise alcohol and this generates free radicals
Symptoms of alcoholic liver disease
Abdominal pain Weight loss/gain Anorexia Fatigue Jaundice Nausea and vomiting If severe - peripheral oedema, abdominal distension
Signs of alcoholic liver disease
Hepatomegaly Palmar erythema Ascites Asterixis Telangiectasia Pruritus Fever Dupytren's contracture Gynaecomastia Hypogonadism Dementia Peripheral neuropathy
Investigations for alcoholic liver disease
FBC - anaemia, leucocytosis, thrombocytopaenia, raised MCV
LFTs
- Raised AST and ALT
- AST>ALT
- Raised or normal ALP
- Raised GGT and bilirubin
- Normal or prolonged PT and INR
U&Es
Hepatic US
- Hepatomegaly, fatty liver, liver cirrhosis, liver mass, splenomegaly, ascites, portal hypertension
Consider - hepatic virology, iron, ferritin, transferrin, copper, caeruolplasmin, AMA, ANA, AMSA, alpha 1 antitrypsin
Biopsy
Management of alcoholic liver disease
Removal alcohol
Thiamine for Wernicke-Korsakoff syndrome
Diazepam for DTs
Decrease weight, smoking cessation
Nutritional supplements and multivitamins
Immunisation - influenza, pneumococcal, hep A and B
Corticosteroids - if hepatic encephalopathy
Sodium restriction and diuretics
Liver transplant
Prognosis of alcoholic liver disease
Improves with alcohol cessation
With abstinence 5 year survival = 90%, without = 60%
If advanced liver disease (jaundice, ascites, haematemesis = 35%
Epidemiology of fatty liver disease
40-60 years NAFLD is equal in both sexes More prevalent in Hispanics NAFLD 20-30% of population Non-alcoholic steatohepatitis - 5% Fatty liver is found in 50% of heavy alcohol users and 94% of obese individuals
Define fatty liver disease
Steatosis - accumulation of fat in liver
Steatohepatitis - fatty liver causing inflammation
Can be divided into:
- Alcoholic fatty liver disease
- NAFLD - non alcoholic fatty liver disease
Only difference is alcoholic consumption
When inflammation is present can get NASH non-alcoholic steatohepatitis which can progress to cirrhosis and HCC
Causes of fatty liver disease
Metabolic syndrome - T2DM, impaired glucose tolerance, central obesity, dyslipidemia, hypertension
PCOS
Alcohol excess
Starvation, rapid weight loss, gastric bypass surgery
Total parenteral nutrition and re-feeding syndrome
Hep B, C, HIV
Medication - Amiodarone, tamoxifen, steroids, tetracycline, oestrogens, methotrexate
Wilson’s disease
Pathophysiology of fatty liver disease
Accumulation of triglycerides and other lipids in hepatocytes
Result of defective fatty acid metabolism, mitochondrial damage (alcohol), insulin resistance or impaired receptors and enzymes
Histologically undistinguished from alcoholic hepatitis
Mallory’s hyaline neutrophil inflammation and pericellular fibrosis
Symptoms of fatty liver disease
Most do not have symptoms
May have fatigue, malaise or RUQ pain
If advanced - ascites, oedema, jaundice
Investigations for fatty liver disease
Definitive diagnosis only from biopsy + histology
- LFTs: mildly raised ALT relative to AST, reverses as disease progresses
- If raised GGT then alcohol likely cause
- Fasting lipids and glucose
- FBC
- Viral serology
- US - hyperechoic bright imaging
- Elastography can be used to determine degree of fibrosis
- CT or MRI can show extent of disease
- SteatoTest, NAFLD fibrosis score
- BIOPSY
Management of fatty liver disease
Alcohol related fatty liver is managed with abstinence and diet
- Weight loss
- Control co-morbidities: BP, diabetes, cholesterol
- Exercise
- medications: statins, fibrates,, metformin
- Bariatric surgery
- Regular follow up
Prognosis of fatty liver disease
Steatosis - 1-2% develop cirrhosis in 202 years
Steatohepatitis - 10-12% have cirrhosis in 8 years
Define cirrhosis
Loss of normal hepatic architecture due to fibrosis with nodular regeneration.
Implies irreversible liver disease and is the final stage of chronic disease from a variety of causes
80-90% of liver parenchyma needs to be destroyed before signs appear
Aetiology of cirrhosis
Alcohol Hep B Hep C Unknown cause NAFLD NASH Primary biliary cirrhosis Autoimmune Primary sclerosing cholangitis Wilson's disease Haemochromatosis Alpha 1 antitrypsin deficiency Chronic R heart failure Budd-Chiari syndrome Drugs - methotrexate
Pathophysiology of cirrhosis
Chronic injury to the liver results in inflammation, necrosis and eventually fibrosis
Fibrosis is initiated by activation of stellate cells and upregulation of receptors for proliferative and fibrogenic cytokines
Normal matrix replaced by collagens
Loss of endothelial fenestrations –> impaired liver function
Fibrosis causes distortion of hepatic vasculature and can lead to increased intrahepatic resistance and portal hypertension
Portal hypertension can lead to oesophageal varices, hypoperfusion of kidneys, salt and water retention,
Micronodular - caused by alcohol damage and biliary tract disease
Macronodular - chronic hepatitis
Signs and symptoms of cirrhosis
Vague symptoms: anorexia, nausea and weight loss
In a long period of compensate cirrhosis, patient is well.
Decompensation leads to:
- Hepatocellular failure
- Ascites
- Portal hypertension
- HCC
- Osteoporosis
- Increased infections - particularly spontaneous bacterial peritonitis
Investigations for liver cirrhosis
Dependent on clinical suspicion of aetiology
- Hypoalbuminaemia
- FBC: anaemia, thrombocytopenia, macrocytosis
- U&E: hyponatraemia, poor renal function would indicate hepatorenal function
- Raised ferritin in haemochromatosis
Imaging
- US of liver +/- CT/MRI to detect complications
- CXR: elevated diaphragm and pleural effusion
- BIOPSY: gold standard
Management of cirrhosis
Delay progression and prevent or treat any complications
- Cholestyramine for pruritus
- Preventative for osteoporosis
- Prophylactic antibiotics in upper GI bleeding
- Stop alcohol
- Regular exercise
Complications of cirrhosis
Anaemia Thrombocytopaenia Coagulopathy Oesophageal varices Ascites Spontaneous bacterial peritonitis HCC Cirrhotic cardiomyopathy Hepatopulmonary syndrome Portopulmonary hypertension
Prognosis of cirrhosis
Calculated by Childs-Pugh-Turcotte Classification
Raised score has decreased prognosis
Define portal hypertension
Abnormally high pressure in the hepatic portal vein
Hepatic venous pressure gradient >10mmHg
Anatomy of hepatic portal vein
Veins that enter portal hepatic vein
- Superior mesenteric vein (from small intestine)
- Splenic vein
- Inferior mesenteric vein (from large intestine)
Aetiology of portal hypertension
Pre-hepatic
- Portal vein thrombosis
- Splenic vein thrombosis
- Extrinsic compression (tumours)
Hepatic
- Cirrhosis
- Chronic hepatitis
- Myeloproliferative diseases
- Idiopathic
- Toxins
- Nodular
Post-hepatic
- Budd-Chiari syndrome
- Constrictive pericarditis
- R heart failure
- Anti-leukaemic drugs/radiation from veno-occlusion of small veins
Pathophysiology of portal hypertension
Increased vascular resistance in portal venous system - liver damage activates stellate cells and myofibroblasts contributing to abnormal blood flow patterns
Increased blood flow in portal veins
- Splanchnic arteriolar vasodilation caused by excessive release of endogenous vasodilators
Increased portal pressure opens up collaterals connecting to portal and systemic venous system
Collaterals to portal system
Gastro-oesophageal junction - producing varices
Rectum
Left renal vein
Diaphragm
Anterior abdominal wall via umbilical vein (caput medusae)
Budd-Chiari syndrome
Occlusion of hepatic vein leading to collateral opening up within the liver with blood diverting though caudate lobe whose short hepatic veins drain directly into IVC
Presentation of portal hypertension
Haematemesis or melaena Lethargy, irritability and changes in sleep (encephalopathy) Increased abdominal girth, weight gain Abdominal pain, fever (SBP) Pulmonary involvement Caput medusae Splenomegaly Ascites Jaundice Spider naevi Palmar erythema Confusion, asterixis Gynaecomastia Testicular atrophy Hyperdynamic circulation - bounding pulse, low BP, warm peripheries
Investigations for portal hypertension
LFTs, U&Es, glucose, FBC, clotting screen
Abdominal US - liver and spleen size, ascites, portal blood flow and thrombosis
Doppler for direction of flow in vessels
Elastography for fibrosis
Measure hepatic venous pressure gradient
Liver biopsy
Management of portal hypertension
Difficult to treat = treat underlying cause
- Beta blockers +/- nitrates or shunt procedure
- Salt restriction and diuretics
- Terlipressin and octreotide can assist control of variceal bleeding
- TIPS: transjugular intraheptatic portosystemic shunt
Connects portal and hepatic veins using stent.
Decompresses portal system
Prevents re-bleeding and ascites
Has a role in: hepatorenal syndrome, hepatic hydrothorax, hepatopulmonary syndrome, Budd-Chiari syndrome
Complications of portal hypertension
Bleeding from gastric or oesophageal varices (90% get varices, 33% of these bleed) Ascites (SBP, hepatorenal syndrome) Portopulmonary hypertension Liver failure hepatic encephalopathy Cirrhotic cardiomyopathy
Presentation of hepatomegaly
Vague symptoms: weight loss, reduced appetite, lethargy
May have jaundice, ascites etc.
Smooth hepatomegaly: hepatitis, CHF, sarcoid, early cirrhosis
Craggy hepatomegaly: HCC or 2y tumours
Aetiology of hepatomegaly
Apparent - low lying diaphragm, early cirrhosis
Venous congestion failure - viral hepatitis, EBV, CMV, malaria, constrictive pericarditis, hepatic vein obstruction
Autoimmune liver disease
Biliary disease - extrahepatic obstruction, primary biliary cirrhosis, primary sclerosing cholangitis
2y cancers, HCC
Amyloidosis, sarcoidosis
Sickle cell, thalassaemia, haemolytic anaemia, myeloma, leukaemia, lymphoma
Haemochromatosis, Wilson’s disease, porphyuria, NAFLD
Drugs - alcohol, drug induced hepatitis
In children - TORCH (toxoplasmosis, other, rubella, CMV, herpes simplex)
Aetiology of ascites
Cirrhosis (transudate) Malignancy (exudate) Heart failure Nephrotic syndrome - hypoproteinaemia Protein losing enteropathy TB Pancreatitis Hypothyroidism Iatrogenic Budd-Chiari syndrome
Causes of haemorrhagic ascites
Malignancy
Ruptured ectopic pregnancy
Abdominal trauma
Acute pancreatitis
Classification of ascites
Only if not affected and not associated with hepatorenal syndrome
- Grade 1: MILD, only detected on US
- Grade 2: MODERATE: moderate symmetrical distension of abdomen
- Grade 3: LARGE - marked abdominal distension
Pathophysiology of ascites
Transudates are the result of increased pressure in hepatic portal vein e.g. due to cirrhosis
Exudates are actively secreted due to inflammation - raised protein, LDH and WCC, low pH and glucose
Sodium and water retention occurs due to peripheral arterial vasodilation and consequent reduction in effective blood volume
- NO, ANP and prostaglandins vasodilation
- Decrease blood volume leads to increase RAAS
Portal hypertension - exerts a local hydrostatic pressure and leads to increase production of lymph and transudate into peritoneal cavity
Low serum albumin - may contribute to low plasma oncotic pressure
Signs and symptoms of ascites
Abdominal distension and discomfort
Weight gain - due to water retention
Nausea
Appetite suppression - due to compression of bowels and stomach
Increased dyspnoea due to limited venous return from legs and impaired lung expansion
Stigmata of liver disease and cirrhosis
Virchow’s node - if peritoneal carcinoma
Investigations for ascites
- Confirm presence of ascites
- Find cause
- Assess complications
- FBC, U&Es, LFTs, TFTs, clotting
US - can detect small amounts and show causative pathology
CXR - pleural effusion, pulmonary mets, heart failure
Aspiration of fluid
- Neutrophils > 250 = SBP
- Measure protein - transudate or exudate
- Cytology for malignant cells
Management of ascites
Salt and water intake restriction
Regular weights
- Spironolactone (monitor for hyperkalaemia)
- Loop diuretics (Monitor for hyponatraemia)
- Paracentesis - if large or refractory ascites
- TIPS if > 3 per month
- Catumaxamab
Define hepatic encephalopathy
Spectrum of neuropsychiatric abnormalities in patients with liver disease after exclusion of other known brain disease.
Can be covert or overt
Grades 0-4
0 - subclinical, normal mental status (minimal changes in memory, co-ordination or concentration)
1 - mild confusion, euphoria or depression
2 - drowsiuness, lethargy, gross defects in performing mental tasks
3 - rousable, unable to perform mental tasks, disorientated in time and place. incomeprehensible speech
4 - coma +/- response to painful stimuli
Precipitating factors for hepatic encephalopathy
high dietary protein
GI bleeding Constipation Infection, including SBP Diuretic therapy TIPS Surgery Progressive liver damage Development of HCC Sedative drugs
Features of hepatic encephalopathy
Personality changes Intellectual impairment Decreased level of consciousness Reversal of sleep rhythm Nausea and vomiting Confusion Irritability Weakness Coma Hyper-reflexia Increased tone Fetor hepaticus - sweet smell to breath Asterixis Constructional apraxia Decreased mental function
Investigations in hepatic encephalopathy
Diagnosed clinically Will have deranged LFTs - Psychometric tests - Increased ammonia levels - EEG (decreased alpha waves) - Visual evoked response
Management of hepatic encephalopathy
Early diagnosis
Management of precipitating factors
- Lactulose - decreased nitrogen load from gut
- Antibiotics - lower amino acid production by decreasing concentration of ammonia forming colonic bacteria
(neomycin, vancomycin, metronidazole)
- IV fluids as required
Pathophysiology of hepatic encephalopathy
Ammonia is by product of colonic bacteria catabolism of nitrogenous sources such as ingested protein and secretion of urea nitrogen
Impaired liver function leads to impaired ammonia clearance
Cirrhosis leads to portosystemic shunting which also decreased ammonia clearance
increased ammonia = alteration of cerebral concentration of aminio acids and this affects neurotransmitter synthesis
Phases of drug metabolism
Phase 1 - oxidation reactions catalysed by enzyme’s of which P450 is the most important
Phase 2 - conjugation
Formation of covalent bond between drug and endogenous substrate
- usually in hepatic cytoplasm, makes it water soluble for excretion
Rules for prescribing in liver disease
No general rules for modifying drug doses in liver disease
Changes in metabolism alters efficacy and toxicity
If hypoalbuminaemia then protein bound drugs may be present in toxic amounts
Decreased clotting - increased sensitivity to anticoagulants
Fluids overload can worse ascites
Avoid hepato-toxic drugs
Renal control of BP
Decreased BP = decreased renal perfusion at juxtaglomerular apparatus
= RENIN secretion from kidneys
Angiotensinogen – renin –> angiotensin I
Angiotensin I –ACE (lungs –> angiotensin II
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Functions of angiotension II
1. Increased sympathetics
2. Na+ and water retention
3. Aldosterone secretion
4. Arteriolar vasoconstriction
5. ADH secretion from posterior pituitary (increase water absorption)
6. Increased thirst
Epidemiology of renovascular disease
7% of over 65s increases with age FHx of CV or renovascular disease More common in younger women (fibromuscular dysplasia) and older men (atherosclerosis) Increased in Caucasians
RFs Obesity Hyperlipidaemia Hypertension Renal impairment Other vascular disease Diabetes Smoking
Aetiology of renal hypoperfusion
Renal artery atheroma Fibromuscular dysplasia Prolonged hypotension Embolic renal disease Renal artery or aortic dissection Neurofibromatosis Renal AV malformation Takayasu's arteritis
Pathophysiology of renovascular disease
Atherosclerosis is most common
Normally develops at renal artery ostium on luminal surface of aorta/proximal renal artery
Atheroma obstructs blood flow
Chronic renal ischaemia
In India and Far East - Takayasu’s arteritits most common
Fibromuscular dysplasia affects distal renal artery
Presentation of renovascular disease
Patients are often asymptomatic
Hypertension
- Abrupt severe onset in middle or older aged patients
Biochemical or clinical evidence of renal impairment during treatment ARB or ACEi
Decompensation of congestive heart failure - recurrent episodes of acute pulmonary oedema
Investigations for renovascular disease
U&Es Blood glucose 24 hour urine protein excretion Urinalysis for RBCs and casts Serology to rule out SLE or vasculitis Lipid profile - likely to have atherosclerotic disease Renal US
If thought to be amenable to intervention - angiography
Management of renovascular disease
Optimise vascular profile - smoking cessation, diabetes, statins, hypertensive therapy
Avoid ACEi and ARBs
Avoid nephrotoxic drugs
Angioplasty and stenting is first line (indicated in pulmonary oedema, severe for refractory hypertension)
Open/endovascular surgery to reconstruct stenosed artery
Complications of renovascular disease
End organ damage from uncontrolled hypertension CKD AKI Decreased renal function Refractory angina
