Gastro Flashcards
Gastrin
G cells in antrum of the stomach
stimulus - * Stomach Distension
* extrinsic nerves Inhibited by:
* low antral pH * somatostatin
actions - ↑ HCL= ↑acidity, pepsinogen and IF secretion, ↑ gastric motility, ↑ gastric mucosa breakdown (trophic effect)
CCK
↑ secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, ↓ gastric emptying, trophic effect on pancreatic acinar cells, induces satiety
Secretin
↑ secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, ↓ gastric acid secretion, trophic effect on pancreatic acinar cells
VIP
Stimulates secretion by pancreas and intestines, inhibits acid and pepsinogen secretion
Somatostatin
↓ acid and pepsin secretion, ↓ gastrin secretion, ↓ pancreatic enzyme secretion, ↓ insulin and glucagon secretion
inhibits trophic effects of gastrin, stimulates gastric mucous production
Principle mediators of acid secretion
Gastrin
* V agal stimulation
* Histamine
Factors increasing acid secretion
Gastrinoma
* Small bowel resection (removal of inhibition)
* Systemic mastocytosis (elevated histamine levels)
* Basophilia
Factors decreasing acid secretion
Drugs: H2-antagonists, PPIs
* Hormones: secretin, VIP, GIP, CCK
Pharyngeal Pouch
posteromedial diverticulum or herniation through Killian’s dehiscence. Killian’s dehiscence is a triangular area in the wall of the pharynx between the thyropharyngeus and cricopharyngeus muscles. It is more common in older patients and is 5 times more common in men
Pharyngeal Pouch Features
- Dysphagia
- Regurgitation
- Aspiration
- Neck swelling which gurgles on palpation
- Halitosis (noticeably unpleasant odors exhaled in breathing)
Travellers’ diarrhea
may be defined as at least 3 loose to watery stools in 24 hours with or without one or more of abdominal cramps, fever, nausea, vomiting or blood in the stool. The most common cause is Escherichia coli
Escherichia coli
Common amongst travellers
Watery stools
Abdominal cramps and nausea
Giardiasis
Prolonged, non-bloody diarrhea
Cholera
Profuse, watery diarrhea
Severe dehydration resulting in weight loss Not common amongst travellers
Shigella
Bloody diarrhea
Vomiting and abdominal pain
Staphylococcus aureus
Severe vomiting
Short incubation period
Campylobacter
Most common cause in UK
A flu-like prodrome
followed by crampy abdominal pains
fever and diarrhoea which may be bloody Complications include Guillain-Barre syndrome
Bacillus cereus
Two types of illness are seen
vomiting within 6 hours
diarrhoeal illness occurring after 6 hours
Amoebiasis
Gradual onset bloody diarrhea abdominal pain and tenderness may last for several weeks
Incubation period
1-6 hrs: Staphylococcus aureus, Bacillus cereus
* 12-48 hrs: Salmonella, Escherichia coli
* 48-72 hrs: Shigella, Campylobacter
* > 7 days: Giardiasis, Amoebiasis
Clostridium difficile
Features:
Diarrhea
* Abdominal pain
* If severe, toxic dilatation
* Sometimes seen in nosocomial outbreaks
Clostridium difficile
pseudomembranous colitis.
clindamycin is historically associated with causing Clostridium difficile
Second and third generation cephalosporins (e.g ciprofloxacin) are now the leading cause.
Clostridium difficile
Diagnosis
Management:
is made by detecting Clostridium difficile TOXIN (CDT) in the stool
Management:
* ORAL metronidazole for 10-14 days
* If severe or not responding to metronidazole then ORAL vancomycin may be used.
* For life-threatening infections a combination of oral vancomycin and intravenous metronidazole
should be used
Bacterial overgrowth
gold standard investigation of bacterial overgrowth is small bowel
aspiration and culture.
Other possible investigations include:
* Hydrogen breath test
* 14c-xylose breath test
* 14c-glycocholate breath test: used increasingly less due to low specificity
Exotoxins
enerally released by Gram positive bacteria with the notable exceptions of Vibrio
cholerae and some strains of E. coli
Diphtheria toxin
diphtheric membrane’ on tonsils caused by necrotic mucosal cells.
Systemic distribution may produce necrosis of myocardial, neural and renal tissue.
Staph. aureus exotoxins
lead to acute gastroenteritis, toxic shock syndrome and Staphylococcal scalded
skin syndrome
Cholera toxin
causes activation of adenylate cyclase leading to ↑ in cAMP levels, which in turn leads to ↑ chloride secretion.
Acute treatment of variceal hemorrhage
ABC: patients should ideally be resuscitated prior to endoscopy
* Correct clotting: FFP, vitamin K
* Vasoactive agents: terlipressin is currently the only licensed vasoactive agent. It has been shown to be of benefit in initial hemostasis and preventing rebleeding. It acts by Constriction of the splanchnic vessels (contraindicated in
IHD, use Octreotide as alternative)
* Prophylactic antibiotics have been shown in multiple meta-analyses to ↓ mortality in patients
with liver cirrhosis
Prophylaxis of variceal hemorrhage
Propranolol: ↓ rebleeding and mortality compared to placebo
* Endoscopic variceal band ligation (EVL) is superior to endoscopic sclerotherapy. It should be
performed at two-weekly intervals until all varices have been eradicated. Proton pump inhibitor cover is given to prevent EVL-induced ulceration
Barrett’s Esophagus
efers to the metaplasia of the lower esophageal mucosa, with the usual squamous epithelium being replaced by columnar epithelium. There is ↑ risk of esophageal adenocarcinoma, estimated at 50-100 folds.
Barrett’s Esophagus
Histological features:
Histological features: the columnar epithelium may resemble that of either the cardiac region of the stomach or that of the small intestine (e.g. with goblet cells, brush border)
Barrett’s Esophagus Management
Management
* Endoscopic surveillance with biopsies
* Low grade dysplasia: high-dose proton pump inh
GERD investigation
24hr esophageal pH monitoring is gold standard investigation in GERD
Indications for upper GI endoscopy:
- Age > 55 years
- Symptoms > 4 weeks or persistent symptoms despite treatment
- Dysphagia
- Relapsing symptoms
- W eight loss
Pain on swallowing (odynophagia)
typical of esophageal candidiasis, a well documented
complication of inhaled steroid therapy
Esophageal cancer
Dysphagia
Dysphagia may be associated with weight loss, anorexia or vomiting during eating Past history may include Barrett’s esophagus, GERD, excessive smoking or alcohol use
Oesophagitis
candidiasis
here may be a history of HIV or other risk factors such as steroid inhaler use
Achalasia
Dysphagia of both liquids and solids from the start
Heartburn
Regurgitation of food - may lead to cough, aspiration pneumonia etc
Pharyngeal pouch
More common in older men
Represents a posteromedial herniation between thyropharyngeus and cricopharyngeus muscles
Usually not seen but if large then a midline lump in the neck that gurgles on palpation
Typical symptoms are dysphagia, regurgitation, aspiration and chronic cough. Halitosis may occasionally be seen
Systemic sclerosis
Other features of CREST syndrome may be present, namely Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia
Myasthenia gravis
Other symptoms may include extraocular muscle weakness or ptosis Dysphagia with liquids as well as solids
Globus hystericus
May be history of anxiety Symptoms are often intermittent
Achalasia:
Clinical features
Dysphagia of BOTH liquids and solids
* Typically variation in severity of symptoms
* Heartburn
* Regurgitation of food - may lead to cough, aspiration pneumonia etc
* Malignant change in small number of patients
* 7% ↑ in risk of squamous cell carcinoma
The gold standard test for achalasia
osophageal manometry
Achalasia Manometery finding
Loss of peristalsis in distal esophagus, failure of LOS to relax during swallowing and (i.e ↑ residual relaxing pressure)
Loss of peristalsis in distal esophagus BUT ↓ resting LOS p
scleroderma Manometery finding
Loss of peristalsis in distal esophagus BUT ↓ resting LOS pressure
Achalasia: investigations
Manometry: excessive LOS tone which doesn’t relax on swallowing - considered most important diagnostic test
* Barium swallow shows grossly expanded esophagus, fluid level
* CXR: wide mediastinum, fluid level
Achalasia: Treatment
Treatment
* Intra-sphincteric injection of botulinum toxin
* Heller cardiomyotomy
* Balloon dilation
* Drug therapy has a role but is limited
by side-effects
Boerhaave’s syndrome -
Features:
Features:
* Complete transmural (full-thickness) laceration or perforation of the esophagus, distinct from Mallory-Weiss syndrome, a nontransmural esophageal tear also associated with vomiting.
* Perforation is almost always on Left side of Lower esophagus.
* Gastric contents enter the mediastinum and pleural cavity, if one were to perform a pleural fluid
aspirate; one is likely to aspirate gastric contents!
* ♂ > ♀ and typically between 50-70 years old
* Other clinical features that may suggest the diagnosis include odynophagia and surgical
emphysema in the neck
Boerhaave’s syndrome -
Causes:
Causes:
* Vomiting (against a closed glottis) in eating disorders such as bulimia
* Rarely: Extremely forceful coughing - Obstruction by food
Boerhaave’s syndrome Diagnosis:
Diagnosis:
* Radiographs show mediastinal gas, effusion, and later pneumothorax.
Esophagram is used to confirm leak, first with water-soluble contrast, then barium if no leak demonstrated.
Boerhaave’s syndrome Management:
Early operation after appropriate resuscitation offers the best chance of survival.
Dyspepsia: Causes
- NSAIDs
- Bisphosphonates * Steroids
The following drugs may cause reflux by reducing lower esophageal sphincter (LOS) pressure - Calcium channel blockers*
- Nitrates*
- Theophyllines
In 2004 NICE published guidelines for the management of dyspepsia in primary care.
Chronic gastrointestinal bleeding
* Progressive unintentional weight loss
* Progressive difficulty swallowing
* Persistent vomiting
* Iron deficiency anemia
* Epigastric mass
* Suspicious barium meal
Deciding whether urgent referral for endoscopy is needed
Recent in onset rather than recurrent and
* Unexplained (e.g. New symptoms which cannot be explained by precipitants such as NSAIDs)
and
* Persistent: continuing beyond a period that would normally be associated with self-limiting
problems (e.g. Up to four to six weeks, depending on the severity of signs and symptoms)
Helicobacter pylori
Gram negative bacteria associated with a variety of gastrointestinal problems, principally peptic ulcer disease
Helicobacter pylori eradication 7 day course of
H. pylori eradication 7 day course of:
* PPI + amoxicillin + clarithromycin, or
* PPI + metronidazole + clarithromycin
H pylori’s Associations
Peptic ulcer disease (95% of duodenal ulcers, 75% of gastric ulcers)
* Gastric cancer
* B cell lymphoma of MALT tissue (eradication of H pylori 80% causes regression)
* Atrophic gastritis
H Pylori tests
Urea breath test
Patients consume a drink containing carbon isotope 13 (13C) enriched urea
* Urea is broken down by H. pylori urease
* After 30 mins patient exhale into a glass tube
* Mass spectrometry analysis calculates the amount of 13C CO2
* Sensitivity 95-98%, specificity 97-98%
* Used to confirm eradication
H Pylori tests Rapid urease test
Rapid urease test (e.g. CLO test)
* Biopsy sample is mixed with urea and pH indicator
* Color change if H pylori urease activity
* Sensitivity 90-95%, specificity 95-98%
H Pylori tests Serum antibody
Serum antibody
* Remains positive after eradication
* Sensitivity 85%, specificity 80%
H Pylori tests Culture of gastric biopsy
Histological evaluation alone, no culture
* Sensitivity 95-99%, specificity 95-99%
Peutz-Jeghers syndrome
AD
autosomal dominant condition characterized by numerous hamartomatous polyps in the gastrointestinal tract. It is also associated with pigmented freckles on the lips, face, palms and soles.
Peutz-Jeghers syndrome Genetics
Autosomal dominant
* Responsible gene encodes serine threonine
kinase LKB1 or STK11
Peutz-Jeghers syndrome Features
- Hamartomatous polyps in GI tract (mainly small bowel)
- Pigmented lesions on lips, oral mucosa, face, palms and soles
- classical histological appearance of smooth muscle “arborisation”
- Intestinal obstruction e.g. Intussusception
- Gastrointestinal bleeding
Esophageal Cancer
Until recent time esophageal cancer was most commonly due to a squamous cell carcinoma but the incidence of adenocarcinoma is rising rapidly. Adenocarcinoma is now (since 2010) the most common type of oesophageal cancer and is more likely to develop in patients with a history of gastro-esophageal reflux disease (GERD) or Barrett’s.
The majority of tumours are in the middle third of the esophagus.
Esophageal Cancer
Squamous Cell Carcinoma
Risk factors:
* Smoking
* Alcohol
* Achalasia
* Plummer-vinson syndrome
* Rare: coeliac disease, scleroderma
* Sensetive to radiotherapy
Risk factors:Adenocarcinoma
GERD
* Barrett’s esophagus
Gastric cancer
Epidemiology
* Overall incidence is decreasing, but incidence of tumors arising from the cardia is increasing
* Peak age = 70-80 years
* More common in Japan, China, Finland and Columbia than the west
* More common in ♂s, 2:1
Gastric cancer - Associations
- H. pylori infection (although it is protective against esophageal cancer)
- Blood group A: gAstric cAncer
- Gastric adenomatous polyps
- Pernicious anemia
- Smoking
- Diet: salty, spicy, nitrates
- May be negatively associated with duodenal ulcer
Gastric cancer Investigation
Diagnosis: endoscopy with biopsy
* Staging: CT or endoscopic ultrasound - endoscopic ultrasound has recently been shown to be
superior to CT
Colorectal cancer:
Screening:
Most cancers develop from adenomatous polyps therefore a screening program could theoretically ↓ mortality
* Main techniques being evaluated are faecal occult blood (FOB) testing, sigmoidoscopy and colonoscopy
* Fecal occult blood testing is the only method to have been proven to ↓ mortality (by about 20%) in trials. Sensitivity can be ↑ by DNA analysis for the APC gene
Causes for a positive fecal occult blood testing are:
2-10%: cancer (colorectal cancer, gastric cancer)
* 20-30% adenoma or polyps
* Bleeding peptic ulcer
* Angiodysplasia of the colon
Colorectal cancer: Staging and Grading:
The Dukes staging system is widely employed for classifying colorectal cancers and is a useful predictor of survival. Tumour grade and depth of penetration are also important:
* Duke A (Stage I) defines a tumour confined to the bowel wall (i.e. mucosa and submucosa).
* Duke B (Stage II) invades through the muscle wall.
* Duke C (Stage III) involves lymph nodes.
* After this the patient presents with metastatic disease at distant sites (Stage IV).
colorectal cancer Prognostic indicators post complete resection includes:
Poorly differentiated histological type.
* Tumour adherence to adjacent organs.
* Bowel perforation.
* Colonic obstruction at the time of diagnosis.
* Venous invasion by the tumour.
Management:
- Surgical excision of a colonic carcinoma is the main treatment
- Adjuvant chemotherapy (5-fluorouracil and folinic acid) is warranted in high-risk stage II
Causes for a positive fecal occult blood testing are:
* 2-10%: cancer (colorectal cancer, gastric cancer)
* 20-30% adenoma or polyps
* Bleeding peptic ulcer
* Angiodysplasia of the colon
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colonic carcinomas and all stage III colonic carcinomas.
* The addition of oxaliplatin has been shown to improve survival in these patients in a large
multicentre trial (MOSAIC study), but the additional drug can cause a severe peripheral
neuropathy.
* Adjuvant radiotherapy is used in rectal carcinomas. This is combined with chemotherapy in
stage II and III rectal carcinomas to reduce the risk of local as well as metastatic relapse.
sporadic colon cancer
eries of genetic mutations. For example, more than half of colon cancers show allelic loss of the adenomatous polyposis coli (APC) gene. It is believed a further series of gene abnormalities e.g. activation of the K-ras oncogene, deletion of p53 and DCC tumour suppressor genes lead to invasive carcinoma
HNPCC,
utosomal dominant condition, is the most common form of inherited colon cancer.
Proximal colon cancer
Amsterdam criteria for HNPCC
At least 3 family members with colon cancer
* The cases span at least two generations
* At least one case diagnosed before the age of 50 years
HNPCC screening for ↑ risk group:
- Colonoscopy every 2 years from 20 to 40 years age then annually
- Check mutation in DNA or mismatched repair gene.
Familial Adenomatous Polyposis (FAP)
rare autosomal dominant condition which leads to the formation of hundreds of polyps by the age of 30-40 years
mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5.
=total colectomy with ileo-anal pouch formation in their twenties.
Gardner’s syndrome
A variant of FAP called Gardner’s syndrome can also feature osteomas of the skull and
mandible,
jaw osteomas which give a “cotton-wool” appearance to the jaws,
as well as multiple odontomas, Congenital Hypertrophy of the Retinal Pigment Epithelium
(CHRPE)
NICE recommend the following patients are referred urgently (i.e. within 2 weeks) to colorectal services for investigation:
Patients > 40 years old, reporting rectal bleeding with a change of bowel habit towards looser stools and/or ↑ stool frequency persisting for 6 weeks or more
* Patients > 60 years old, with rectal bleeding persisting for 6 weeks or more without a change in bowel habit and without anal symptoms
* Patients > 60 years old, with a change in bowel habit to looser stools and/or more frequent stools persisting for 6 weeks or more without rectal bleeding
* Any patient presenting with a right lower abdominal mass consistent with involvement of the large bowel
* Any patient with a palpable rectal mass
* Unexplained iron deficiency anemia in men or non-menstruating women (Hb < 11 g/dl in
men, < 10 g/dl in women)
Zollinger-Ellison Syndrome
s condition characterized by excessive levels of gastrin, usually from a gastrin secreting tumour usually of the duodenum or pancreas.
30% MEN 1
Zollinger-Ellison Syndrome clinical presentation
typically presents with multiple gastroduodenal ulcers causing abdominal pain, diarrhea and malabsorption. High-dose proton pump inhibitors are needed to control the symptoms.
Zollinger-Ellison Syndrome
Diagnosis
Fasting gastrin levels, the single best screen test: done in 3 different days as the gastrin secretion is pulsatile
* Secretin stimulation test: considered +ve if there is ↑ in gastrin >200 pg/mL after secretin injection (Normally Secretin supresses gastrin, but in ZE, it simply shows that the source of gastrin is not the stomach and it is somewhere else like pancresae)
Zollinger-Ellison Syndrome Management:
- If not mets, surgical resection is the cure
- Octreotide can be used to alleviate symptoms with interferon and chemotherapy to attempt cure
non respectable tumor - PPI is used to control symptoms in actute stages
Gastric MALT Lymphoma
Associated with H. pylori infection in 95% of cases
* Good prognosis
* If low grade then 80% respond to H. pylori eradication
* Paraproteinemia may be present
VIPoma
VIPoma
* 90% arise from pancreas
* Large volume diarrhea (secretory type due to enterocytes stimulatioin)
* W eight loss
* Dehydration
* Hypokalemia, hypochlorhydria (refers to states where the production of gastric acid is low)
VIP (vasoactive intestinal peptide)
- Source: small intestine, pancreas
- Stimulation: neural
- Actions: stimulates secretion by pancreas and intestines, inhibits acid and pepsinogen secretion
Angiodysplasia associated with
aortic stenosis
The association between angiodysplasia and aortic stenosis is thought to be caused by von Willebrand factor (vWF) being proteolysed in the turbulent blood flow around the aortic valve. vWF is most active in vascular beds with high shear stress, such as angiodysplasia, and deficiency of vWF increases the bleeding risk from such lesions
Angiodysplasia diagnosis and management
Diagnosis
* Colonoscopy
* Mesenteric angiography if acutely bleeding
Management
* Endoscopic cautery or argon plasma coagulation
* Antifibrinolytics e.g. Tranexamic acid
* Estrogens may also be used
Acute Pancreatitis:GET SMASHED
Gallstones
* Ethanol
* Trauma
* Steroids
* Mumps (other viruses include Coxsackie B)
* Autoimmune (e.g. Polyarteritis nodosa), Ascaris infection
* Scorpion venom
* Hypertriglyceridemia, Hyperchylomicronemia**, Hypercalcemia, Hypothermia
* ERCP
* Drugs (azathioprine, mesalazine*, didanosine, bendroflumethiazide, furosemide, pentamidine,
steroids, sodium valproate)
* ↑ Degree burn of large skin area with significant inhalation injury
Rare features associated with pancreatitis include:
Ischemic (Purtscher) retinopathy (cotton wool spots seen on fundoscopy) - may cause temporary or permanent blindness. This condition may be seen following head trauma and in conditions such as acute pancreatitis, fat embolisation, amniotic fluid embolisation, and vasculitic diseases.
poor prognosis factors pancreatitis
- Age > 55 * WBC > 16 * Urea > 16
- Glucose > 11 * Alb < 30
- ALT > 250
- Ca+ < 1
- LDH > 350 * PO2 < 8
- Hematocrit ↓ >10% * Base deficit > 4
- Fluid loss > 6L
marker of severity in acute pancreatitis
CRP
Chronic Pancreatitis
features
Around 80% of cases are due to alcohol excess with up to 20% of cases being unexplained.
Features of chronic pancreatitis:
* Pain is typically worse 15 to 30 minutes following a meal
* Steatorrhoea: symptoms of pancreatic insufficiency usually develop between 5 and 25 years
after the onset of pain
* Diabetes mellitus develops in the majority of patients. It typically occurs more than 20 years
after symptom begin
Chronic Pancreatitis investigations
nvestigation
* Abdominal x-ray shows pancreatic calcification in 30% of cases
* CT is more sensitive at detecting pancreatic calcification
* Functional tests: pancreolauryl and Lundh tests may be used to assess exocrine function if
imaging inconclusive
chronic pancreatitis: Management
- Pancreatic enzyme supplements
- Analgesia
- Antioxidants: limited evidence base - one study suggests benefit in early disease
Pseudocysts:
ncommon complication of acute pancreatitis and are localised collections of pancreatic fluid and debris, usually in the lesser sac. They are initially contained within a fragile wall of granulation tissue which eventually forms a fibrous capsule.
Pseudocysts: diagnosis and management
iagnosis: they cannot be diagnosed until more than 6 weeks after the acute attack, and may present with:
* Abdominal pain or a mass.
* Fever
* Persistently raised amylase and liver function tests.
Management:
* Small pseudocysts usually resolve spontaneously
* > 6cm in diameter seldom disappear spontaneously and may lead to complications such as
hemorrhage and infection. They are usually managed by endoscopic or percutanous drainage or surgical intervention.
Pancreatic Cancer: Epidemiology and general points:
Incidence in the West: 9 cases per 100 000 and it’s increasing over the last 20 years.
* 60% are ♂
* 5-year survival rate: 2%
* K-ras is the most common oncogene in this condition
* Insulinomas are the commonest form of endocrine tumours of the pancreas
* Majority of cases occur in patients over the age of 60
Pancretice cancer associations
Smoking (with a twofold increase in incidence)
* Diabetes
* Chronic pancreatitis
* Hereditary pancreatitis
* Hereditary non-polyposis colorectal carcinoma
* Multiple endocrine neoplasia
* Peutz-jeghers syndrome
* BRCA2
* Dysplastic naevus syndrome
Pancreatic cancer diagnosis
Contrast CT is used for diagnosis and assessment of invasion
* ERCP restricted to palliative care
* CA 19-9
* U/S abdomen is less reliable when the tumor is in the body or tail
Cowden’s syndrome
defect in the PTEN tumour suppressor gene.
- Hamartomatous polyps of the GI tract(1st)
- oral mucosal papillomas, palmoplantar keratoses and trichilemmomas (benign tumours of hair follicles)
Ulceractive colitis complications
- PSC
- Colorectal Ca
Ulceractive colitis histology
No inflammation beyond submucosa (unless fulminant disease) - inflammatory cell infiltrate in lamina propria
* neutrophils migrate through the walls of glands to form crypt abscesses
* LOSS of goblet cells and mucin from gland epitheli
Ulceractive colitis pathology
nflammation always starts at rectum and never spreads beyond ileocaecal valve
* Continuous disease
* Associated with pANCA antigen
Ulceractive colitis radiology
Barium enema
* loss of haustrations
* superficial ulceration, ‘pseudopolyps’ * long standing disease: colon is
narrow and short -‘drainpipe colon’
chrons pathogy
Lesions may be seen anywhere from the mouth to anus
* Skip lesions may be present
* Associated with ASCA (Anti-
Saccharomyces Cerevisiae Antibodies
Crohns histolgy
Inflammation in all layers from mucosa to serosa
* goblet cells * granulomas
Crohns Small bowel enema
high sensitivity and specificity for examination of the terminal ileum
* strictures: ‘Kantor’s string sign’
* proximal bowel dilation
* ‘rose thorn’ ulcers
* fistulae
Ulcerative Colitis Inducing remission
Treatment depends on the extent and severity of disease
* Rectal aminosalicylates or steroids: for distal colitis rectal mesalazine has been shown to be superior to rectal steroids
* Oral aminosalicylates or steroids
* Severe colitis should be referred to
hospital
UC Maintaining remission
Oral aminosalicylates e.g. Mesalazine
Patients with concomitant UC and PSC are at risk of….
colonic cancer, and it is recommended that they be screened annually with colonoscopy.
Criteria to determine colitis severity include:
Stool frequency >6/day
* ESR > 30 mm/hr
* HR > 90 bpm
* Temp > 37.8°C in 2 out of 4 days
* Anemia (Hb <75% predicted)
in UC Factors increasing risk of cancer
Disease duration > 10 years
* Patients with pancolitis
* Onset before 15 years old
* Unremitting disease
* Poor compliance to treatment
Crohns - active disease treatment
Mesalazine: whilst evidence base is limited widely used in active disease
* Steroids (oral, topical or intravenous)
* Azathioprine is used as a second-line treatment in active disease
* Mercaptopurine (also called 6-mercaptopurine, 6-MP)
* Methotrexate is used in patients intolerant of azathioprine or refractory disease. Usually given intramuscularly, but not effective in maintaining remission. Significant anemia is a contra- indication for methotrexate.
* Infliximab is useful in refractory disease and fistulating crohn’s. Patients typically continue on azathioprine or methotrexate
Whipple’s disease
rare multi-system disorder caused by Tropheryma whippelii infection. It is more common in those who are HLA-B27 positive and in middle-aged men
Whipple’s disease Features
Malabsorption: diarrhea, weight loss
* Large-joint arthralgia (seronegative arthropathy)
* Lymphadenopathy
* Skin: hyperpigmentation and photosensitivity
* Pleurisy, pericarditis
* Neurological symptoms (rare): ophthalmoplegia, dementia, seizures, ataxia, myoclonus
Investigation Whipple’s disease
Investigation
* Jejunal biopsy shows deposition of macrophages containing Periodic acid-Schiff (PAS) granules
* ↑ CRP and ESR
* Hypoalbuminemia
Microscopic colitis: is defined by the triad of:
- Watery diarrhea
- Normal colonoscopy
- ↑ Inflamation of the lamina propria of the colon.
Microscopic colitis:Association:
NSAIDs
* Omeprazole, Lansoprazole
* Ticlopidine
* Cimetidine
IBS First-line pharmacological treatment
Pain: antispasmodic agents
* Constipation: laxatives but avoid lactulose
* Diarrhea: loperamide is first-lin
Second-line pharmacological treatment
* low-dose tricyclic antidepressants (e.g. amitriptyline 5-10 mg) are used in preference to selective serotonin reuptak
Coeliac Disease disease process
s caused by sensitivity to the protein gluten. Repeated exposure leads to villous atrophy which in turn causes malabsorption.
Conditions associated with coeliac disease
nclude dermatitis herpetiformis (a vesicular, pruritic skin eruption) and autoimmune disorders (type 1 diabetes mellitus and autoimmune hepatitis). It is strongly associated with HLA-DQ2 (95% of patients) and HLA-B8 (80%) as well as HLA-DR3 and HLA-DR7
Signs and symptoms coeliac
? Chronic or intermittent diarrhea
? Failure to thrive or faltering growth (in children)
? Persistent or unexplained gastrointestinal symptoms including nausea and vomiting
? Prolonged fatigue (‘tired all the time’)
? Recurrent abdominal pain, cramping or distension
? Sudden or unexpected weight loss
? Unexplained iron-deficiency anemia, or other unspecified anemia
? Recurrent mouth ulcers
Complications coeliac
- Anemia: iron, folate and vitamin B12 deficiency (folate deficiency is more common than vitamin B12 deficiency in coeliac disease)
- Hyposplenism
- Osteoporosis
- Lactose intolerance
- Enteropathy-associated T-cell lymphoma of small intestine
- Subfertility, unfavourable pregnancy outcomes
- Rare: esophageal cancer, other malignancies
coeliac Diagnosis
Combination of immunology and jejunal biopsy. Villous atrophy and immunology normally reverses on a gluten-free diet.
Immunology coeliac
Tissue transglutaminase (TTG) antibodies (IgA) are first-choice according to NICE
* Endomyseal antibody (IgA)
* Anti-gliadin antibody (IgA or IgG) tests are NOT recommended by NICE
* Anti-casein antibodies are also found in some patients
Jejunal biopsy coeliac
- Villous atrophy
- Crypt hyperplasia
- ↑ in intraepithelial lymphocytes
- Lamina propria infiltration with lymphocytes
Tropical Sprue:
this disease is most common in the Carribbean and the Far-East. It is characterized by a picture of small intestinal malabsorption and the cause is thought to be infectious in origin.
Tropical Sprue:Diagnosis:
Diagnosis:
* Jejunal biopsy reveals:
o Mild villous atrophy
o ↑ villous crypts
o Mononuclear cellular infiltrates
o Enlarged epithelial cells
o Large nuclei caused by folate and/or vitamin B12 deficiency.
Tropical Sprue:treatement
eatment:
* Tetracyclines 250mg qds up to 6 months
* Ampicillin may be used as an alternative in patients who are intolerant of tetracyclines.
* Folate and B12 deficiencies should also be corrected
* Complete recovery is possible with appropriate therapy.
Jejunal Villous Atrophy:
Coeliac disease
* Tropical sprue
* Hypogammaglobulinemia
* Gastrointestinal lymphoma
* Whipple’s disease
* Cow’s milk intolerance
Toxic Megacolon:
Management:
* Toxic dilatation can be treated medically for 12-24 hours with IV and rectal hydrocortisone but if there is then no improvement in the triad of
o Pulse }
o Stool frequency
o Colon dilatation
THEN urgent colectomy.
Short Bowel Syndrome:
resentation:
* Diarrhoea
* Steatorrhoea
* Malabsorption manifestation: Weight loss, anemia, osteoporosis/osteomalacia, electrolyte
disturbances and hypovolemia.
Management:
* In patients with > 100cm of jejunum, oral intake is still possible. Diarrhoea may reduce with lactose exclusion or with a course of metronidazole to eradicate bacterial overgrowth.
* In patients with < 100cm of jejunum, total parenteral nutrition is recommended.
Melanosis coli
disorder of pigmentation of the bowel wall. Histology demonstrates pigment- laden macrophages. It is associated with laxative abuse, especially anthraquinone compounds such as
senna
Spontaneous bacterial peritonitis (SBP
assw liver cirrosis
Paracentesis: neutrophil count > 250 cells/ul
SBP Management
ntravenous cefotaxime is usually given
* Patients who have had an episode of SBP should be on prophylactic antibiotics
Alcoholic liver disease is a marker of poor prognosis in SBP.
Ascites: by serum-ascites albumin gradient ↑ SAAG (>1.1 g/dL) causes: ( PORTAL HYPERTEN_
irrhosis
* Alcoholic hepatitis
* Schistosomiasis
* Fulminant hepatic failure
* Budd–Chiari syndrome
* Acute or chronic portal vein obstruction
* Cardiac diseases
* Spontaneous bacterial peritonitis
secondary to cirrhosis.
Ascites: by serum-ascites albumin gradient↓ SAGG (<1.1 g/dL) causes:
Nephrotic syndrome Protein losing enteropathy Peritoneal carcinomatosis Tuberculous peritonitis Pancreatic duct leak Biliary ascites.
Bilirubin:
Bilirubin is derived from the breakdown of heme in the red blood cells within the
reticuloendothelial system.
o The unconjugated bilirubin then binds albumin and is taken up by the liver.
o In the liver it is conjugated which then makes it water-soluble and thus allows it to be
excreted into the urine.
o Normally total serum bilirubin is measured; however, the unconjugated (indirect bilirubin)
and conjugated (direct bilirubin) portions can be.
ALT vs AST
ALT is more specific to the Liver, as AST is also found in cardiac and skeletal muscle and red blood cells.
In chronic Liver disease ALT >AST, once cirrhosis established AST >ALT
The extremes of the ratio of AST:ALT can also be helpful:
>2 suggests alcoholic liver disease.
<1.0 suggests nonalcoholic liver disease.
Albumin
sensitive marker of hepatic function, but not useful in the acute stages as it has a long half life (20 days).
Gamma-glutamyltransferase (GGT)
also related to the bile ducts. Typically elevated in cholestasis (with elevated ALP) but, if ALP normal, suggests induction of hepatic metabolic enzymes (e.g alcohol or enzyme-inducing drugs).
- Alkaline phosphatase (ALP) -
comes mainly from the cells lining bile ducts but also in bone. Marked elevation is typical of cholestasis (often with elevated GGT) or bone disorders (usually normal GGT). Isoenzyme analysis may help identify source. It is physiologically increased when there is increased bone turnover (e.g. adolescence) and is elevated in the third trimester of pregnancy (produced by the placenta).
Hepatomegaly common causes:
Cirrhosis: if early disease, but later liver ↓ in size. Associated with a non-tender, firm liver
* Malignancy: metastatic spread or primary hepatoma. Associated with a hard, irregular. Liver
edge
* Right heart failure: firm, smooth, tender liver edge. May be pulsatile
Primary Biliary Cirrhosis
chronic liver disorder typically seen in middle-aged ♀s (♀:♂ ratio of 9:1). The aetiology is not fully understood although it is thought to be an autoimmune condition, with HLA DR3 association. Interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis, which may eventually progress to cirrhosis. The classic presentation is itching in a middle-aged woman
pbc Associations
Sjogren’s syndrome (seen in up to 80% of patients)
* Rheumatoid arthritis
* Systemic sclerosis
* Thyroid disease
* Membranous GN
* RTA
pbc Clinical features
Clinical features
* Early: may be asymptomatic (e.g. Raised ALP on routine LFTs) or fatigue, pruritus
* Cholestatic jaundice
* Hyperpigmentation, especially over pressure points
* Xanthelasmas, xanthomata
* Also: clubbing, hepatosplenomegaly
* Late: may progress to liver failure
Diagnosis
pbc
Anti-mitochondrial antibodies (AMA) M2 subtype in 98% of patients and are highly specific.
* Smooth muscle antibodies in 30% of patients
* Raised serum IgM
pbc Management
Management
* Median survival is 7-10 yrs, but ↓ to 2 yrs if jaundice is present
* Pruritus: cholestyramine
* Fat-soluble vitamin supplementation
* Ursodeoxycholic acid
* Liver transplantation e.g. If bilirubin > 100 (PBC is a major indication) - recurrence in graft can occur but is n
Primary biliary cirrhosis - the M rule
IgM
* Anti-Mitochondrial antibodies, M2 subtype
* Middle aged ♀s
Primary sclerosing cholangitis
biliary disease of unknown aetiology characterized by inflammation and fibrosis of intra and extra-hepatic bile ducts
Primary sclerosing cholangitis assw
Associations
* Ulcerative colitis: 4% of patients with UC have PSC, 80% of patients with PSC have UC
* Crohn’s (much less common association than UC)
* HIV
Primary sclerosing cholangitis features
- Cholestasis
- Hepatomegaly
- Intermittent jaundice
Primary sclerosing cholangitis Investigation
Investigation
* ERCP is the standard diagnostic tool, showing multiple biliary strictures giving a ‘beaded’ appearance
* MRCP is superior to ERCP
* ANCA may be positive
* There is a limited role for liver
biopsy, which may show fibrous, obliterative cholangitis often described as ‘onion skin’
Primary sclerosing cholangitis complications
omplications
* Cholangiocarcinoma (in 10%)
* ↑ risk of colorectal cancer
Management:
* Liver transplantation, survival post transplant is 90% although rejection is high. Indication for transplantation:
Wilson’s Disease
autosomal recessive disorder characterized by excessive copper deposition in the tissues. Metabolic abnormalities include ↑ copper absorption from the small intestine and ↓ hepatic copper excretion. Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13.
Wilson’s Disease
Features result from excessive copper deposition in the tissues, especially the brain, liver and cornea:
* Liver: hepatitis, cirrhosis
* Neurological: speech and behavioral
problems are often the first manifestations.
Also: tremor, chorea
* Kayser-fleischer rings →
* Renal tubular acidosis (esp. Fanconi
syndrome)
* Hemolysis
* Blue nails
Wilson’s Disease diagnosis
Diagnosis
* ↓ serum ceruloplasmin
* ↑ 24hr urinary copper excretion
* Slit lamp: Kayser-Fleischer ring
Management
* D-penicillamine: chelates copper 1.5-2g/day in divided dose then 0.75-1.5g/day maintenance
* Trientine
* Zinc
Gilbert’s syndrome
is an autosomal recessive* condition of defective bilirubin conjugation due to a deficiency of UDP glucuronyl transferase. The prevalence is approximately 1-2% in the general population. Viral infections are common triggers for a rise in the bilirubin in patients with Gilbert’s
Features
* Isolated hyperbilirubinemia
* Unconjugated hyperbilirubinemia (i.e. Not in urine)
* Jaundice may only be seen during an intercurrent illness
Investigation and management
* Investigation: rise in bilirubin following prolonged fasting or IV nicotinic acid
* No treatment required
Dubin-Johnson syndrome
is a benign autosomal recessive disorder resulting in hyperbilirubinemia (conjugated, therefore present in urine). It is due to a defect in the canalicular multispecific organic anion transporter (cMOAT) protein. This causes defective hepatic bilirubin excretion.
Features:
* ↑ of conjugated
* NO elevation of liver enzymes (ALT, AST).
* Usually asymptomatic but may be diagnosed in early infancy based on laboratory tests.
* Liver biopsy shows dark granules in the hepatocytes (thought to be due to melanin deposition)
* Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are
asymptomatic and have normal life spans.
Rotor syndrome:
are, relatively benign autosomal recessive bilirubin disorder of unknown origin. It is a distinct disorder, yet similar to Dubin-Johnson Syndrome — both diseases cause an increase in conjugated bilirubin.
Crigler-Najjar Syndrome:
s a rare disorder affecting the metabolism of bilirubin, which results in high levels of unconjugated bilirubin and often leads to brain damage in infants.
Bile Acid Malabsorption:
is a cause of chronic diarrhea. It can result from malabsorption secondary to gastro-intestinal disease or be a primary disorder. Treatment with bile acid sequestrants is often effective.
Types:
* Type 1: Bile acid malabsorption, secondary to ileal resection, or ileal inflammation (e.g. in Crohn’s disease)
* Type 2: Idiopathic bile acid malabsorption, Primary bile acid diarrhea
* Type 3: Secondary to various gastrointestinal diseases including cholecystectomy, vagotomy,
small intestinal bacterial overgrowth, radiation enteropathy, celiac disease, chronic pancreatitis, etc.
Bile Acid Malabsorption: Diagnosis:
Diagnosis:
* SeHCAT test (selenium homocholic acid taurine or tauroselcholic acid): nuclear test involves two scans a week apart and only very limited radiation exposure. Retention of SeHCAT at 7 days is normally above 15%. Values less than 15% predict a response to bile acid sequestrants. The SeHCAT test measures multiple cycles of bile acid excretion and reabsorption over 7 days. This test is not licensed in the USA, and is underutilized even where it is available
* Fecal bile acid quantfication or the 14C-glycocholic breath test are no longer in routine clinical use.
hep b
Hepatitis B: Basics
* Incubation period (weeks) = 6-20
* Double-stranded DNA virus
* Spread: body fluids + vertical
* Chronic disease in 5-10%
* Vaccination available
At risk groups who should be vaccinated include hep b
healthcare workers, intravenous drug users, sex workers, close family contacts of an individual with hepatitis B, individuals receiving blood transfusions regularly, chronic kidney disease patients who may soon require renal replacement therapy, prisoners, chronic liver disease patients
hep b emus
Immunization
* Contains HBsAg adsorbed onto aluminum hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology
* Most schedules give 3 doses of the vaccine with a recommendation for a one-off booster 5 years following the initial primary vaccination
Anti-HBs level (mIU/ml) over 100
Indicates adequate response, no further testing required. Should still receive booster at 5 years
Anti-HBs level (mIU/ml) 10 - 100
Suboptimal response - one additional vaccine dose should be given. If immunocompetent no further testing is required
Anti-HBs level (mIU/ml) under 10
Non-responder. Test for past or previous infection. Give further vaccine course (i.e. 3 doses again) with testing following. If still fails to respond then HBIG would be required for protection if exposed to the virus
hep b complications
- Chronic infection (5-10%)
- Fulminant liver failure (1%)
- Hepatocellular carcinoma
- GBS
- Glomerulonephritis (memberanoproliferative)
- Polyarteritis nodosa
- Cryoglobulinemia (more with Hepa C than Hepa B)
heb b management
Management:
- Pegylated interferon-alpha used to be the only treatment available. It reduces viral replication in up to 30% of chronic carriers. A better response is predicted by being ♀ < 50 years old, low HBV DNA levels, non-Asian, HIV negative, high degree of inflammation on liver biopsy
- However due to the side-effects of pegylated interferon it is now used less commonly in clinical practice. Oral antiviral medication is increasingly used with an aim to suppress viral replication (not in the dissimilar way to treating HIV patients)
- Examples include lamivudine, tenofovir and entecavir
Treatment of Hepa B is based on:
Abnormal ALT in at least 1 occasion
* Liver biopsy shows fibrosis
* Hepa B viremia >105 HBV DNA copies per mL
surface antigen (HBsAg)
first marker to appear and causes the production of anti-HBs
* HBsAg normally implies acute disease (present for 1-6 months)
- If HBsAg is present for > 6 months then
implies chronic disease
Anti-HBs implies
immunity (either exposure or immunization)
HBeA
results from breakdown of core antigen from infected liver cells as is therefore a marker of infectivity (e=infectivity)
Anti-HBc implies
Anti-HBc implies previous (or current) infection. IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months (c=current or recent)
Primary Biliary Cirrhosis
chronic liver disorder typically seen in middle-aged ♀s (♀:♂ ratio of 9:1). The aetiology is not fully understood although it is thought to be an autoimmune condition, with HLA DR3 association. Interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis, which may eventually progress to cirrhosis. The classic presentation is itching in a middle-aged woman
Primary Biliary Cirrhosis Associations
Sjogren’s syndrome (seen in up to 80% of patients)
* Rheumatoid arthritis
* Systemic sclerosis
* Thyroid disease
* Membranous GN
* RTA
Primary Biliary CirrhosisClinical features
Clinical features
* Early: may be asymptomatic (e.g. Raised ALP on routine LFTs) or fatigue, pruritus
* Cholestatic jaundice
* Hyperpigmentation, especially over pressure points
* Xanthelasmas, xanthomata
* Also: clubbing, hepatosplenomegaly
* Late: may progress to liver failure
Primary Biliary
- Anti-mitochondrial antibodies (AMA) M2 subtype in 98% of patients and are highly specific.
- Smooth muscle antibodies in 30% of patients
- Raised serum IgM
The Only MRCP Notes You’ll Ever Need
231 / 546 www.sudamedica.com
Management - Median survival is 7-10 yrs, but ↓ to 2 yrs if jaundice is present
- Pruritus: cholestyramine
- Fat-soluble vitamin supplementation
- Ursodeoxycholic acid
- Liver transplantation e.g. If bilirubin > 100 (PBC is a major indication) - recurrence in graft can occur but is not usually a problem. 5 y
Primary sclerosing cholangitis
s a biliary disease of unknown aetiology characterized by inflammation and fibrosis of intra and extra-hepatic bile ducts
Primary sclerosing cholangitis
Associations
* Ulcerative colitis: 4% of patients with UC have PSC, 80% of patients with PSC have UC
* Crohn’s (much less common association than UC)
* HIV
Primary sclerosing cholangitis
Features
* Cholestasis
* Hepatomegaly
* Intermittent jaundice
Investigation
* ERCP is the standard diagnostic tool, showing multiple biliary strictures giving a ‘beaded’ appearance
* MRCP is superior to ERCP
* ANCA may be positive
* There is a limited role for liver
biopsy, which may show fibrous, obliterative cholangitis often described as ‘onion skin’
Wilson’s Disease
Wilson’s Disease is an autosomal recessive disorder characterized by excessive copper deposition in the tissues. Metabolic abnormalities include ↑ copper absorption from the small intestine and ↓ hepatic copper excretion. Wilson’s disease is caused by a defect in the ATP7B gene located on chromosome 13.
Wilson’s Disease Features
Features result from excessive copper deposition in the tissues, especially the brain, liver and cornea:
* Liver: hepatitis, cirrhosis
* Neurological: speech and behavioral
problems are often the first manifestations.
Also: tremor, chorea
* Kayser-fleischer rings →
* Renal tubular acidosis (esp. Fanconi
syndrome)
* Hemolysis
* Blue nails
Wilson’s Disease
iagnosis
* ↓ serum ceruloplasmin
* ↑ 24hr urinary copper excretion
* Slit lamp: Kayser-Fleischer ring
Management
* D-penicillamine: chelates copper 1.5-2g/day in divided dose then 0.75-1.5g/day maintenance
* Trientine
* Zinc
Dubin-Johnson syndrome
is a benign autosomal recessive disorder resulting in hyperbilirubinemia (conjugated, therefore present in urine). It is due to a defect in the canalicular multispecific organic anion transporter (cMOAT) protein. This causes defective hepatic bilirubin excretion.
Hepatitis C
ikely to become a significant public health problem in the UK in the next decade. It is thought around 200,000 people are chronically infected with the virus. At risk groups include intravenous drug users and patients who received a blood transfusion prior to 1991 (e.g. hemophiliacs). Hepa C is an RNA virus.
hep c transmission
Transmission
* Risk of transmission during a needle stick injury is about 2%
* The risk of transmitting the virus during sexual intercourse is probably less than 5%
* Vertical transmission rate from mother to child is about 6% (high viral load at delivery ↑ risk)
* Breast feeding is not contraindicated in mothers with Hepatitis C
Features
* After exposure to the Hepatitis C virus less than 20% of patients develop an acute hepatitis
heb c comps
Complications
* Chronic infection (80-85%) - only 15-20% of patients will clear the virus and will hence the majority will develop chronic hepatitis C
* Cirrhosis (20-30% of those with chronic disease)
* Hepatocellular cancer
* Cryoglobulinemia
Autoimmune hepatitis
is condition of unknown etiology which is most commonly seen in young ♀s. Recognized associations include other autoimmune disorders, hypergammaglobulinemia and HLA B8, DR3. Three types of autoimmune hepatitis have been characterized according to the types of circulating antibodies present
Autoimmune hepatitis type 1 - antibodies
Anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)
Autoimmune hepatitis type 2 - antibodies
Anti-liver/kidney microsomal type 1 antibodies (LKM1)
Autoimmune hepatitis type 3 - antibodies
Soluble liver-kidney antigen
Diagnosis combination of deranged LFTs combined with secondary amenorrhea in a young female
autoimmune hepatitis
Autoimmune hepatitis features
Features
* May present with signs of chronic liver disease
* Acute hepatitis: fever, jaundice etc (only 25% present in this way)
* Amenorrhea (common)
* ANA/SMA/LKM1 antibodies, raised IgG levels
* Liver biopsy: inflammation extending beyond limiting plate ‘piecemeal necrosis’, bridging
necrosis
Autoimmune hepatitis management
Management
* Steroids, other immunosuppressants e.g. Azathioprine
* Liver transplantation
Alcoholic Hepatitis: features
Features:
* Increased serum transaminase
* Macrocytosis
* Thrombocytopenia
* Poor hepatic synthetic function
* Leucocytosis irrespective of infection
* Increased acute phase reactants.
* AST/ALT is usually > 2.
* Liver enzymes do not exceed 500.
Zieve’s Syndrome:
occurs in patients with excessive alcohol consumption with hemolysis and severe hyperlipidemia, abdominal pain, transient mildly raised bilirubin. It usually occurs in males and resolves once alcohol consumption is stopped.
Non-alcoholic fatty liver disease (NAFLD
- Steatosis - fat in the liver
- Steatohepatitis - fat with inflammation, non-alcoholic steatohepatitis (NASH), see below
- Progressive disease may cause fibrosis and liver cirrhosis
NAFLD is thought to represent the hepatic manifestation of the metabolic syndrome and hence insulin resistance is thought to be the key mechanism leading to steatosis
Non-alcoholic fatty liver disease (NAFLD) associated factors
Associated factors
* Obesity
* Hyperlipidemia
* T2DM
* Jejunoileal bypass
* Sudden weight loss/starvation
Non-alcoholic fatty liver disease (NAFLD) features
eatures
* Usually asymptomatic
* Hepatomegaly
* ALT is typically greater than AST
* Increased echogenicity on ultrasound
Liver Cirrhosis: types
Micronodular cirrhosis is associated with alcohol liver disease. Liver Cirrhosis: * Macronodular cirrhosis is associated with chronic hepatitis.
* Granuloma formation is not classically seen in cirrhosis.
Hepatocellular carcinoma (HCC) RF
Other risk factors include:
* Alpha-1 antitrypsin deficiency * Hereditary tyrosinosis
* Glycogen storage disease
* Aflatoxin
Drugs: oral contraceptive pill, anabolic steroids * Porphyria cutanea tarda
* ♂ sex
* Diabetes mellitus, metabolic syndrome
Hepatocellular carcinoma (HCC) features
Features
* Drugs: oral contraceptive pill, anabolic steroids * Porphyria cutanea tarda
* ♂ sex
* Diabetes mellitus, metabolic syndrome
* Tends to present late
* Features of liver cirrhosis or failure may be seen: jaundice, ascites, RUQ pain, hepatomegaly,
pruritus, splenomegaly
* Possible presentation is decompensation in a patient with chronic liver disease
Hepatocellular carcinoma (HCC) screening and management
creening with ultrasound (+/- alpha-fetoprotein) should be considered for high risk groups such as:
* Patients liver cirrhosis secondary to hepatitis B & C or hemochromatosis
* Men with liver cirrhosis secondary to alcohol
Management options
* Early disease: surgical resection
* Liver transplantation
* Radiofrequency ablation
* Transarterial chemoembolisation
* Sorafenib: a multikinase inhibitor
Contraindications to percutaneous liver biopsy
- Deranged clotting (e.g. INR > 1.4)
- Low platelets (e.g. < 60 * 109/l)
- Anemia
- Bile duct obstruction
- Hydatid cyst
- Hemoangioma
- Uncooperative patient
- Ascites
Pyogenic liver abscess: Management
- Drainage (needle aspiration or catheter) should always be performed
- Amoxicillin + ciprofloxacin + metronidazole
- If penicillin allergic: ciprofloxacin + clindamycin
Hepatorenal Syndrome (HRS): what is this
efers to the development of acute renal failure in a patient who has advanced liver disease, who has no identifiable cause of intrinsic renal disease. It usually represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury. Splanchnic vasodilatation appears to play an important role in the decline in renal function in hepatic disease.
Diagnostic criteria have been proposed for the hepatorenal syndrome:
- Chronic or acute hepatic disease with advanced hepatic failure and portal hypertension
- Creatinine > 133 mmol/l that progresses over days to weeks
- Absence of any other apparent cause for the renal disease, including shock, active sepsis,
current nephrotoxic drugs, and the absence of ultrasonographic evidence of obstruction or parenchymal renal disease. It is particularly important to exclude spontaneous bacterial peritonitis, which is complicated with acute renal failure - Urine sodium < 10 meq/l (off diuretics) and protein excretion < 500 mg/day
- Lack of improvement in renal function after volume expansion with 1.5litres of isotonic saline.
type 1 Hepatorenal Syndrome
- Rapidly progressive
- Doubling of serum creatinine to > 221 μmol/L or a halving of the creatinine clearance to less than 20 ml/min over a period of less than 2 weeks
- Very poor prognosis
type 2 Hepatorenal Syndrome
*Slowly progressive *Prognosis poor, but patients may live for longer
Anal fissures common location
are longitudinal or elliptical tears of the squamous lining of the distal anal canal. If present for less than 6 weeks they are defined as acute, and chronic if present for more than 6 weeks. Around 90% of anal fissures occur on the posterior midline
Management of an acute anal fissure (< 6 weeks)
- Dietary advice: high-fiber diet with high fluid intake
- Bulk-forming laxatives are first line - if not tolerated then lactulose should be tried
- Lubricants such as petroleum jelly may be tried before defecation
- Topical anesthetics
- Sits baths: hip baths in hot water for 2–5 minutes followed by cold water for 1 minute
- Topical steroids do not provide significant relief
Management of a chronic anal fissure (> 6 weeks)
The above techniques should be continued
* Topical glyceryl trinitrate (GTN) is first line treatment for a chronic anal fissure
* If topical GTN is not effective after 8 weeks then secondary referral should be considered for
surgery or botulinum toxin
Mesenteric ischemia predisposing factors
- Increasing age
- Atrial fibrillation
- Other causes of emboli: endocarditis
- Cardiovascular disease risk factors: smoking, hypertension, diabetes
Mesenteric ischemia Features
Features
* Abdominal pain
* Rectal bleeding
* Diarrhea
* Fever
* Bloods typically show an elevated WBC associated with acidosis (low HCO3)
Ischemic Colitis:
schemic colitis occurs with greater frequency in the elderly,
most common form of bowel ischemia
causes: Causes of the reduced blood flow can include ↓BP or local factors such as constriction of blood vessels or atheroma in the mesenteric vessels (most common).
Ischemic Colitis: diagnosis
Diagnosis:
* Barium enema results tend to be
abnormal in 90% showing thumbprinting,
an indicative of mucosal edema
* CT is the single best test after plain
radiography
* Colonoscopy is the diagnostic tool of
choice: it shows petechiae, pallor, hyperemia and necrosis
Retropritoneal Fibrosis: associated features
Riedel’s thyroiditis
* Previous radiotherapy
* Sarcoidosis
* Inflammatory abdominal aortic aneurysm
* Drugs: methysergide
