Module 1.3: Liver + Pancreas Flashcards
Summarise the reasoning for the research interest in alcohol
- Sheron, 2010
causes >50% of violent crime + domestic violence
2000 homicides/year
200000 deaths
4x more deaths and disability risk than illicit drugs
cause of 7% of all ill health + early death - BMJ 2013
drinking doubled compared to 40 years ago
1/4 adults in UK drink dangerous amounts
total cost of misuse 21b pounds/year in social/economic harm
Summarise the most effective way of addressing the issues with alcohol
difficult to change social beliefs
MIN UNIT PRICING
- 45p/unit would lead to 220m pounds average annual savings to NHS over 10y
- prevent 714 deaths and 25k hospital admissions
according to Home Office Impact assessment
Organ donations - if swapped to ‘opt out’ system, % of donors would increase
Summarise the metabolism of alcohol
MAJOR PATHWAY
ethanol –> acetaldehyde (enzyme: alcohol dehydrogenase, NAD->NADH)
acetaldehyde –> acetate (enzyme: acetaldehyde dehydrogenase, NAD->NADH)
only occurs in hepatocyte cytosol
MINOR PATHWAY
ethanol –> acetaldehyde (enzyme: cytochrome P4502E1, NAPDH->NAPD)
occurs in smooth ER
Summarise the variation in acetaldehyde dehydrogenase
some people have forms of acetaldehyde dehydrogenase that work faster - THEY ARE ISOENZYMES
ALDH2 is present in 75% of oriental-origin Asian populations –> works slowly –> Acetaldehyde buildup –> unpleasant reactions + FLUSHING
Natural aversion to alcohol –> lower rate of alcoholism in Chinese subject with ALDH2
This is the basis of Disulfiram - inhibits acetaldehyde dehydrogenase –> unpleasant symptoms such as flushing, nausea, tachycardia, dyspnoea, hypotension
BACLOFEN –> GABA receptor agonist –> used as anti-spasmodic –> reduces cravings
Describe the pathogenesis of alcoholic liver disease
Incompletely understood
Risk of alcoholic liver disease related to amount and duration of consumption of alcohol
Only minority of chronic alcohol abusers develop liver disease –> presumably genetic drivers that influence liver disease development
- CENTRILOBAR HYPOXIA
- alcohol metabolism consumes O2 via the NAD pathway - NEUTROPHIL INFILTRATION AND ACTIVATION
- INFLAMMATORY CELL INFILTRATION AND ACTIVATION
- ANTIGENIC ADDUCT FORMATION
- adduct: causes DNA and protein damage by binding to DNA
- acetaldehyde and hydroxylethyl radicals bind to proteins and damage them - INJUROUS PRO-INFLAMMATORY CYTOKINES
- TNF and IL6
- scarring and liver damage
Briefly describe the disease progression in ALD
Normal liver –>/ alcoholic hepatitis (10-35%) –> cirrhosis (?40%)
OR
fatty liver –> cirrhosis (8-20%)
Describe and exlpain the risk factors of ALD
Amount and duration of ethanol ingestion
- for cirrhosis 80g/day for 10-20y required
- – 1 litre wine, 8 cans of beer
Coexisting HepB/HepC infection
- accelerates disease in alcoholics
- 30% prevalence of HeCV in ALD
Malnutrition
- all money spent on alcohol or because alcohol is filling
- worsens severity
Genetic factors
- FEMALE GENDER
- – increased disease risk for a given amount/duration of alcohol intake independent of weight
- STRONG CANDIDATE GENES:
— PNPLA3 - role in hydrolysis of triglycerides
— TM6SF2 - role in VLDL production and secretion
— MBOAT7 - role in neutrophil activation
(Stickel et al 2016)
Epigenetic factors
- how micro-environment within the body affects the genes
- alcohol induced oxidative stress –> histone modification –> altered recruitment of transcriptional machinery and abnormal gene expression –> accelerated cell death and inflammation
(Mandrekar 2011)
Obesity and diabetes
- independent predictors of fibrosis in NASH which has histological similarities to ALD and may share pathogenesis
Concurrent exposure to hepatotoxins
- two hepatotoxins –> greater risk than either alone e.g. paracetamol + alcohol
Decribe the alcoholic steatosis stage of ALD
occurs within hours of binge
Direct effect of etOH
90% of heavy drinkers
accummulation of membrane bound fat droplets + proliferation of smooth ER + gradual distorsion of mitochondria
minimal inflammatory changes
Reversible
Decribe the alcoholic hepatitis stage of ALD
medical emergency - otherwise patients die within a few months
ESSENTIAL FEATURES:
- liver cell necrosis
- mallory bodies (eosinophilic accumulation of cellular material)
- neutrophil infiltration
periventricular or pericentral (viral is periportal)
Other features: bridging necrosis, fatty change, bile duct proliferation, cholestasis, perivenular fibrosis
Decribe the alcoholic fibrosis/cirrhosis stage of ALD
The on-going necrosis of hepatocytes results in regeneration, leading to fibrosis –> nodular, firm liver
Fibrosis - Potentially reversible if abstain from alcohol
TRUE CIRRHOSIS - presence of regenerative nodules –> IRREVERSIBLE
It is worth trying to reverse cirrhosis UNLESS PT HAS DECOMPENSATED
define FIBROSIS of the liver
accumulation of scar protein or ECM, including interstitial collagens, glycoproteins and proteoglycans
What is the main cell involved in the scarring of the liver?
STELLATE CELLS
main source of ECM
normal function is to store Vit A
activated by platelet derived GF + transforming growth factor-1 + endothelin-127
when activated, they lose vitA, proliferate and become fibrogenic
Screening for alcoholism
CAGE
felt the need to cut down
annoyed if criticised
felt guilty about it
eye-opener first thing in the morning
Tx of ALD
few specific therapies
most important intervention = ABSTINENCE
Nutritional supplements: fluids, vitamins (pabrinex), human albumin olution
the idea is to prevent relapse
Liver transplantation in decompensated cirrhosis but pts have to show they can be alcohol abstinent
Tx complications
- ascites, portal hypertension, varices, encephalopathy, HCC
Tx of alcoholic hepatitis
High mortality (40%)
Tx of alcohol withdrawal - CHLORDIAZEPOXIDE
fluids, calories, vitamins (pabrinex), albumin
exclude and tx sepsis, renal impairment, portal hypertnsion etc.
STEROIDS reduce morality in selected cases of Alcoholic Hepatitis
Describe the use of Child-Pugh classification in chronic liver disease
PARAMETERS:
Ascites Bilirubin Albumin PT Encephelopathy
Score 5-6 - GRADE A - well-compensated
Score 7-9 - GRADE B - significant functional compromise
Score 10-15 - GRADE C - decompensated
1/2 year survival:
A - 100/85%
B - 80/60%
C - 45/35%
Describe normal iron metabolism
dietary intake: 10-20mg/day Absorbed: 1-1.5 mg/day Total in body: 4g Iron in Hb: 3g Total iron binding capacity: 250-370 ug/dl
Describe the results of excess iron in the body
Liver: cirrhosis, HCC
Heart: CCF, conducting deficits, arrhythmias, constrictive pericarditis
Endocrine: diabetes, panhypopituitarism, hypogonadotrophism
Joints: chondrocalcinosis
How does excess iron lead to cellular damage?
oxygen derived free radicals are produced through the Fenton reaction which damage proteins, DNA and cell membrane
What are the two forms of iron found in the body
Haem - 10% - Fe2+ - ferrous
non-haem - 90% - Fe3+ - ferric
Explain the process of iron absorption in the body
Ferric iron is reduced to ferrous iron by Duodenal cytochrome b (Dcytb), which is a ferric reductase. Dcytb is expressed in the duodenal brush border.
The ferrous iron is taken up by a divalent metal transporter 1, DMT1
Following uptake iron is either STORED as FERRITIN
or
released by FERROPORTIN 1 (FPN), which is the only exporter that regulates plama iron concs
Once in circulation, iron is oxidised to its ferric form by HEPHAESTIN on intestinal surface or CAERULOPLASMIN in plasma.
Iron binds TRANSFERRIN to be transported
When delivered to a site, it binds to transferrin receptor 1 (TfR1)
Explain the importance of TfR1 in iron absorption
highly expressed in erythroid precursors to ensure increased iron uptake for erythropoiesis
Interaction of transferrin-bound iron with TfR1 results in INVAGINATION of cell membrane
The iron is releaed in the cytoplasm and converted back to Fe2+ by STEAP3
Explain how iron absorption is controlled
by iron responsive elements (IRE) and IRE-binding-proteins (IRP1 and 2)
IRP1 acts as an iron sensor in high oxygen environments
IRP2 acts at physiological oxygen tensions
LOW intracellular Iron –> IRP binding to IRE –> increased DMT1 synthesis + increased ferroportin in duodenum –> increased absorption
Most important regulator = HEPCIDIN
Give examples to causes of excess iron
Dietary: bantu siderosis
erythropoietic siderosis
multiple transfusions
genetic: haemochromatosis
What are the types of haemachromatosis
1 - classic
- – affected protein: HFE
- – inheritance: AR
2A + 2B - juvenile
- – affected protein: haemojuvelin and hepcidin respectively
- – inheritance: AR
3 - Tfr2 haemachromatosis
- – affected protein: Tfr2
- – inheritance: AR
4 - African overload Ferroportin disease
- – affected protein: ferroportin
- – inheritance: AD
X - 1 human case and mouse models
- – affected protein: DMT1
- – inheritance: AR
Summarise the relevance of HFE mutations in haemochromatosis
Autosomal recessive
8-10% of Caucasians are carriers
Most common mutations: C282Y and H63D
apprx 85-90% of those with the phenotype are C282Y homozygous
3-5% are C282Y/H63D heterozygous
Describe the function of Hepcidin
25aa protein
related to defensins - inflammatory marker
UPREGULATED IN:
- bacterial infection
- IL1, IL6
- iron overload
DOWNREGULATED IN:
- iron deficiency
- hypoxia
Hepcidin binds to ferroportin (FPN) and causes DEGRADATION
Results in iron export from enterocytes + macrophages
–> decreased serum iron
When hepcidin expression is decreased, iron absorption and cellular iron export is UPREGULATED resulting in increase in serum iron
Describe the regulation is hepcidin
Depends upon signalling through the bone morphogenic protein (BMP)/SMAD pathway
BMP6 highly expressed in liver
high transferrin-Fe complexes in plasma = hepcidin increased
TfR2 senses high conc and forms complex with BMP and other proteins such as haemojuvelin
The complex activates SMAD signalling pathway causing gene transcription for hepcidin
IN IRON OVERLOAD:
- the complex activates SMAD signalling pathway, causing gene transcription for hepcidin
Describe the role of hepcidin in immunity
Expressed by macrophages - because bacteria need iron rich environments to grow. When activated by bacteria, immune system increases production of hepcidin as a way of restriction infection
Describe the diagnostic criteria for haemochromatosis
RAISED SERUM IRON: 220ug/dL
RAISED TRANSFERRIN SAT: 90% (normal 45%)
RAISED TRANSFERRIN: 50-200 is normal
STAINABLE IRON ON LIVER BIOPSY
HEPATIC IRON INDEX
FERROUS SCAN VIA MRI
Describe the Tx of haemochromatosis
VENESECTION
- 500ml blood = 250 mg Fe
- removal of 10-40g Fe needed
Weekly venesection until transferrin saturation below 50% and ferritin below 50ug/ml
Venesection every 3 months afterwards for maintenance
Define hepatic steatosis
presence of vesicles of fat, predominantly triglycerides, accumulating within hepatocytes
Define NAFLD
presence of hepatic steatosis as part of the metabolic syndrome
steatosis affecting >5% of hepatocytes in the absence of excessive significant alcohol consumption, other liver disease or the consumption of steatogenic drugs
PRIMARY:
- associated with metabolic syndrome
- Obesity
- T2DM
- Dyslipidaemia
SECONDARY:
- alcohol
- drugs
- – steroids, amiodarone, HAART, MTX, tamoxifen
- HepC infection
- parenteral nutrition
Define metabolic syndrome
3+ of
waist circumference > 102cm/88cm M/F TRG > 150 mg/dl HDL<40/50 mg/dl M/F BP >/= 135/85 mmHg fasting glucose >/= 100 mg/dl
INSULIN RESISTANCE is the main pathophysiology
Describe the NAFLD spectrum
statosis –12-40%—> NASH –15%—> Cirrhosis –1%/yr–> HCC
cirrhosis and HCC —-> liver transplantation or death
NAFL = steatosis without hepatocellular injury NASH = steatosis with inflammation and hepatocyte ballooning degeneration
Describe the magnitude of NAFLD
4-34% of population has fatty liver
80% of severely obese
70% of T2diabetics
16% prevalence in normal weight individuals with no metabolic risk factors
Prevalence of NAFLD increases with age - 40% in over 60
Obesity has tripled since 1975 - WHO 2016
Describe the pathogenesis of NAFLD
complex interplay between diet, environment and liver and adipose tissues
poorly understood
Visceral ectopic fat accumulation causes INSULIN RESISTANCE and hepatic necro-inflammation with activation of HEPATIC STELLATE CELLS and increased production of collagen matrix and progression of liver disease
Environmental factors contributing to NAFLD
DIETARY
- high saturated fat content
- high fructose content
- reduced antioxidants
OBESITY
- energy intake > output
- lack of exercise
- increased portions
T2DM
SMALL BOWEL INTESTINAL OVERGROWTH
Genetic factors contributing to NAFLD
FAMILIAL AGGREGATION
- present in 17% in siblings, 37% of parents of overweight children without NAFLD - SCHWIMMER 2009
TWIN STUDIES
- significantly higher in identical twins
- MAKKONEN 2009
What genes were identified as a result of candidate-gene disease association studies in NAFLD?
increased hepatic TAG for PNPLA3 gene
Describe the role of PNPLA3 in NFALD
aka adiponutrin
On Chr22
Associated with severity of lipid accumulation
May sensitise the liver to environmental stressors
exact mechanisms unknown
Describe how NAFLD can be diagnosed
Transaminases
- ALT>AST
- both <3x normal
- normal in 20% of cases although similar liver damage
- ALP/GGT not discriminatory
Components of MS
- raised triglycerides, glucose
- decreased HDL
Ferritin
- raised in 20%, no correlation with Fe overload
- advanced disease
Autoantibodies
- ANA in 20-34%, SMA in 3-6%
- associated with fibrosis
Imaging
- US first line
- enlarged bright liver
- only sensitive when steatosis >33%
Describe the non-invasive scoring systems used in NAFLD
BARD
- BMI > 28
- AST/ALT ration > 1
- Diabetes
NAFLD Fibrosis Score
- age
- BMI
- hyperglycaemia
- AST/ALT
- PLT
- albumin
FIB4
- age
- AST
- ALT
- PLT
Summarise the treatment studied for pts with NAFLD
Lifestyle interventions - reduction in caloric intake
Weight loss therapies
- orlistat
- bariatric surgery
Insulin sensitisers
- metformin
- thiazolidinediones
- incretin based therapies
- DDP4 inhibigofx
Hypertension
- angitension II receptor blockers
Dyslipidaemia
- statins
- fibrates
- Ezetebime
Antioxidants
What is copper found in?
Nuts, mushrooms
What is copper required for?
Enzyme function
e.g.
Superoxide dismutase - free radical detoxification Lysyl oxidase Dopa-B-hydroxylase Tyrosinase Cytochrome C oxidase
Describe normal copper mechanism
Dietary intake: 4mg/day
2mg absorbed, 2mg excreted in bile
absorbed from gut bount to albumin
In circulation, bound to CAERULOPLASMIN or ALPHA-2-GLOBULIN
Transported by transmembrane cation ATPase that has 6 copper binding units
Each binding site is formed from 2 cystin residues linked by two other aa’s
3 ATPases on extracellular domain of the protein
What are the types of APSase transporters in the body?
ATP7a and ATP7b
Normally copper enters the blood from guy via ATP7a
At the liver it is released from albumin and enters the liver sinusoid through CTR1
In hepatocytes, it binds intracellular caeruloplasmin and is transported to the Golgi
At the golgi, it accumulates in vesicles and buds off
Binds to ceruloplasmin to allow transport into bile canaliculi via ATP7b
Describe the genetics of Wilson’s disease
Autosomal recessive
1/90 are carriers
1 in 30k monozygotic frequency –> INCOMPLETE PENETRANCE hence not all are phenotypic
Mutation on 13q - transmembrane cation channel ATPase transporter - ATP7B
250 mutations identified
Describe the pathophysiology of Wilson’s disease
Mutation on ATP7B –> copper enters from guy to hepatocytes FREELY
CANNOT BE SECRETED IN BILE –> accumulation in hepatocytes
lysis and release of free copper
ATP7A is still functional –> can accumulate in BRAIN and EYE
Attempt to excrete causes TOXICITY and renal failure
accumulation in liver causes cholestatic liver disease
Describe the presentation of Wilson’s disease
children and young adults - presents by 30
earlier presentation (<20) likely to present with neuro features
May present as fulminant hepatitis - jaundice, ascites, hepatic/renal failure, hepatocyte necrosis secondary to copper toxicity. Most pts cirrhotic
May present as chronic hepatitis (10-30y)
- jaundice, high transaminases, raised IgG
- neuro changes 2-5y later
Renal changes
- Cu deposited in tubules
KAYSER-FLEISHER RINGS
- Cu accumulation in Descemet’s membrane around the eye
- Requires slit-lamp to visualise
- Seen in older pts
- indicates neuro involvement
Indicate the biochemical features of Wilson’s
High serum Cu
High urinary Cu excretion - 1mg/d
Low biliary copper expression
Low caeruloplasmin (marker, not cause)
Increased Cu deposition in liver, basal ganglia, eye
Low ALP:bilirubin ratio - highly suggestive
How can Wilson’s be diagnosed?
Biochemical markers
MRI - Cu in basal ganglia
Penicillamine trial
- normal urinary copper <38ug/d
- Wilson’s >1mg/d
- – after penicillamine, should drop to 25ug/d
Electron microscopy
Histology on liver biopsy
Quantitative assay of Cu conc on liver biopsy
- Over 250ug/g dry weight = WILSONS
- Under 40ug/d dry weight = EXCLUDED
How is Wilson’s screened for?
Siblings screened via haplotype analysis
- requires two siblings and one parent
Homozygous treated even if asymptomatic
Heterozygotes not treated
Tx of Wilson’s
D-Penicillamine
- Cu chelator
- promotes safe urinary excretion up to 100 mg/d
- Lifelong maintenance needed
- FLTs improve
- neuro complications are PERMANENT
ZINC
- 50 mg
- blocks dietary Cu absorption by inducing cellular methionine
- used once stabilised
Liver transplantation
- in fulminant liver disease
Define chronic pancreatitis
progressive inflammatory changes in the pancreas that results in permanent structural damage which can lead to impaired endocrine or exocrine function
Symptoms of chronic pancreatitis
abdominal pain, features of exocrine (steatorrhoea) or endocrine (diabetes) insufficiency or can be asymptomatic.
Symptoms do not correlate with the rate of structural damage.
Exocrine insufficiency comes first
What are causes of chronic pancreatitis
Most common cause is alcohol
Smoking is a factor
Remaining factors (hypercalcaemia, hypertriglyceridaemic) tend to cause recurrent aculte pancreatitis which eventually results in chronic pancreatitis
Genetics
Describe the pathogenesis of chronic pancreatitis
occurs due to mis-activation of pancreatic enzymes leading to autodigestion
This early activation is influenced by a number of mutations that lead to increased or decreased function of certain proteins
- premature activation of trypsinogen OR its deactivation by chemotrypsin CTRC
SPINK1 is another enzyme that cleaves activated trypsin preventing the pancreas from being autodigested. SPINK1 mutations can lead to increased trypsin activity
what are the forms and causes of familial chronic pancreatitis?
Autosomal Dominant Hereditary Pancreatitis
- PRSS1
Autosomal Recessive Pancreatitis
- CFTR
- SPINK1
Complex genetic risk in sporadic chronic pancreatitis
- Multiple hits
- CFTR, CTRC, SPINK1 heterozygosity
- SPA1 in children
- CLDN2 in adults
Describe the role of PRSS1 in chronic pancreatitis
primary catalysts of zymogen to active enzymes
> 20 mutations recognised
either increase activation of trypsinogen to trypsin (majority) OR confer resistance to breakdown by CTRC
Present by early 20s -> recurrent acute or chronic pancreatitis symptoms
1/3 become exocrine insufficient
40% cumulative risk of pancreatic cancer at 70y
Exacerbated by smoking and DM
Genetic screening recommended
High penetrance (80%)
No Tx but risk can be minimised by lifestyle changes
Describe the role of SPINK1 in chronic pancreatitis
encodes pancreatic secretory trypsin inhibitor
SPINK mutations in 2% of population
Only 1% of carriers have chronic pancreatitis
- need to be homozygous
- require genetic/environmental co-factor
Describe the role of CFTR in chronic pancreatitis
required for excretion of pancreatic enzymes into duodenum
In CF - decreased flushing of enzymes –> more activated in pancreas –> autodigestion
> 2000 polymorphisms
Unlikely to lead to chronic pancreatitis in heterozygous form BUT will do with an environmental or genetic co factor
e.g. CFTR + SPINK heterozygotes
Give examples to the genetic factors identified in sporadic chronic pancreatitis
CTRC - chymotrypsin C gene - produces digestive enzyme that cooperates with active trypsin to degrade trypsin. Can confer moderate risk. Usually found in conjunction with other heterozygous pancreatitis susceptibility variants e.g. CFTR or SPINK1
CLDN2 - co-factor in pts with an alcohol aetiology. Risk dominant in men. Recessive in women
CPA1 - linked to non-alcoholic pancreatitis. Childhood onset
How can chronic pancreatitis be diagnosed?
IMAGING
- CT
- MRI/MRCP
- EUS
LAB
- amylase, fecal elastase (not affected by Creon)
- note that any cause of diarrhoea can cause a drop in fecal elastase
GENETIC
- CFTR
- PRSS1
- SPINK1
Describe the management of chronic pancreatitis
avoid alcohol and tobacco
antioxidants and analgesics
Pancreatectomy in refractory pain with autologous islet cell retransplant
Surveillance for pancreatic cancer
- Ca19-9 - tumour marker
- EUS - most sensitive
- CT can (repeats –> high exposure to radiation
- MRI - annual/every two years
- — possible to alternate bw MRI and EUS
Family Screening
Prognosis in chronic pancreatitis
highest risk of pancreatic cancer in PRSS1
reduced life expectancy if pancreatic cancer develops
Otherwise unaffected
QOL - pain, opiates, exocrine/endocrine insufficiency
Summarise general info re: CF
autosomal recessive
1:2500 caucasians
abnormality of chloride efflux
- Basis of diagnosis - sweat chloride (>60mmol/L)
CFTR is found on chr7
1000 mutations, 200 polymorphysms
70% of cases are due to a DELETION of phenylalanine at 508th position
Groups of CFTR mutations
Class 1
- 7% of pts in Europe
- shortened CFTR protein, sequence prematurely stopped
Class 2
- 85%
- protein fails to reach cell membrane
Class 3
- <4%
- channel not regulated properly
Class 4
- <3%
- reduced chloride conductance
Class 5
- <3%
- reduced synthesis due to incorrect splicing
Class 6
- reduced half-life of Cl-
CLASSES 1-3 –> complete loss of function –> SEVERE
CLASESS 4-5 –> reduction –> MILDER
Describe the pathogenesis of CF
decreased hydration of epithelial cell secretion, leading to increased viscosity of secretion
causes secondary obstructive organ damage
AFFECTS:
- lungs
- pancreas
- liver & biliary
- GI
- sweat glands
- Vas Deferens
Manifestations of CF organ damage
pulmonary - organ damage
pancreases - insufficiency
- endocrine - insulin -diabetes
- exocrine - enzymes - nutrition defs - malnutrition
liver - cirrhosis
biliary - gallstones
GI - obstruction/motility disturbance
Vas deference - sterility
95% of mortality pulmonary related but GI/pancreato-biliary important factors in mobidity
Describe the pancreatic involvement in CF
85% are pancreatic insufficient
Most present in first year of life
Managed by pancreatic enzyme replacement
30% become diabetic later in life
15% are pancreatic SUFFICIENT
- these carry class 4/5 muation
- present in older age
- less severe pulmonary disease
Chronic liver disease in CF
Biliary epithelial cell CFTR leads to ABNORMAL DUCTULAR SECRETION
this leads to
INSPISSATED BILE –> OBSTRUCTION
hydrophobic bile acid retention and immune response to obstruction causes FOCAL BILLIARY CIRRHOSIS
Bile salt metabolism and gut microflora may be involved
Progression to cirrhosis occurs in the first 2 decades
Complications: ascites, variceal haemorrhage, porto-systemic encephalopathy
Distal Intestinal Obstruction Syndrome in CF
Right iliac fossa pain
Associated palpable mass
Evidence of partial or complete SB obstruction
Thickened mucofaeculant material in terminal ileum and right colon
in 15-20% of CF cases
Partial/complete obstruction in 2-3%
Predisposing factors
- dehydration
- poor control of pancreatic insufficiency
- gut motility dysfunction
- low intestinal pH
