Gastroenterology Flashcards
Symptoms/presentation of Dyspepsia?
Oesophageal:
- Odynophagia
- Dysphagia
- Heartburn
Gastric
- Epigastric pain
- nausea and vomiting
- Bloating
General:
- Weight loss
- Appetite increase/decrease
Causes of Dyspepsia?
Oesophageal causes:
- GORD
- Barret’s oesophagus
Gastro-duodenal
- PUD- gastric and duodenal
- Gastric cancer
- Functional dyspepsia
Other causes:
- Biliary diseases (gall stones)
- Jaundice
- Pancreatic diseases
Management of Dyspepsia
- Investigate possible causes for dyspepsia (H pylori, gastric or Oesophageal cancer, Drugs, stress/trauma)
- Refer for OGD- if meets the criteria
- Life-style management: Weight loss (if high BMI), Elevate the head while sleeping, Stop smoking, Reduce alcohol consumption
- Medicinal management: Depends on the cause, Anyone with uninvestigated dyspepsia must be treated with PPI.
WHat is gold standard for dyspepsia
OGD
gold standard for investigating dyspepsia.
What is the criteria to be eligible for OGD?
>55 years
Dyspepsia
Alarm symptoms:
- Weight loss- unintentional
- Persistent GI bleed
- Difficulty swallowing/ inability to swallow
- Persistent vomiting
- Fe deficiency anaemia
- Epigastric mass
- Haematemesis
Pathology of GORD
Three main mechanisms: Poor oesophageal motility decreases clearance of acidic material. A dysfunctional LES allows reflux of large amounts of gastric juice. Delayed gastric emptying can increase the volume and pressure in the reservoir until the valve mechanism is defeated, leading to GORD.
The opening of the LOS results in a backflow/ aspiration of gastric content and acid into the oesophagus causing irritation and inflammation of the lining of the oesophagus. Persistent acid reflux damages the oesophageal mucosa causing complications
Complications of GORD
Oesophagitis, Oesophageal stenosis, Barrett’s oesophagus
Hiatus hernia (but note HH does not always cause GORD)
oesophageal adenocarcinoma
ulceration: rarely→haematemesis, melaena,↓F
Symptoms/Presentations of GORD
- Heartburn: related to meals. Worse lying down / stooping, Relieved by antacids
- Waterbrash
- Regurgitation
- May present with odynophagia
- Nocturnal asthma
- Chronic cough
- Laryngitis, sinusitis
Investigations of GORD
- Isolated symptoms don’t need Ix
- Bloods:FBC
- CXR:hiatus hernia may be seen
- OGD if: >55yrs, Symptoms >4wks, Dysphagia, Persistent symptoms despite Rx, Wt. loss, OGD allows grading by Los Angeles Classification
- Ba swallow:hiatus hernia, dysmotility
- 24h pH testing ± manometry
- pH <4 for >4hr
Management of GORD?
Lifestyle modifications:
- Weight loss
- Stop smoking
- Reduce alcohol
- Elevate head while sleeping
- Small regular meals ≥ 3h before bed
- Stop drugs: NSAIDs, steroids, CCBs, nitrate
Medications
- OTC antacids: Gaviscon, Mg trisilicate
- 1:Full-dose PPI for 1-2mo -Lansoprazole 30mg OD
- 2:No response→double dose PPI BD
- 3:No response: add an H2RA -Ranitidine 300mg nocte
- Control: low-dose acid suppression PR
Surgery
- Nissen Funoplication : usually laparoscopic approach, mobilise gastric funds and wrap around lower oesophagus. Repai diaphram and close any diaphragmatic hiatus
- Complications: gast- bloat: inability to belch/vomit. Dysphagia if wrap too tight
Differential Dx for GORD
- Oesophagitis: Infection: CMV, candida, IBD, Caustic substances / burns
- PUD
- Oesophageal Ca
What is peptic ulceration?
Ulcer in stomach or duodenum - most benign but gastric ulcers can be malignant
- It is a defect of the gastric/ duodenal mucosa which extends to the muscularis mucosa
- Gastric ulcer: defect of the gastric mucosa that is >0.5cm and extends to the muscularis mucosa
- Duodenal ulcer: defect of the duodenal mucosa extending to the muscularis mucosa
Causes of PUD?
H pylori infection
H pylori
NSAIDs and aspirin
Stress- also called curling ulcers
Neuroendocrine tumors- Zollinger Ellison tumour
How does H pylori and NSAIDS/aspirin cause PUD?
H pylori infection
H pylori🡪 produces Urease🡪 breakdown urea into NH3🡪 creates an alkaline environment that favors bacterial colonization🡪 release of bacterial cytotoxins 🡪 cause damage to the mucosa lining of the stomach
NSAIDs and aspirin
Inhibition of COX 1 and COX2🡪 decreased prostaglandins🡪 decreased mucosal blood flow, inhibition of mucosal epithelium proliferation, decreased HCO3-🡪 Damage to the mucosa–> ulcer
Presentation of Barret’s metaplasia?
Appears red as compared to the adjacent pink squamous cell mucosa of the oesophagus
The transition zone (Z line) is shifted upwards
The physiological transformation zone separating the squamous cells from the columnar cells
Pre-malignant change- requires close monitoring
Increased risk of Oesophageal adenocarcinoma
Treatment for Barret’s Oesophagus?
PPI
Biopsies to rule out dysplasia and cancer
Low grade dysplasia= need radio-ablation or endoscopy every 6-12 months taking biopsies every 1cm
Oesophageal adenocarcinoma Pathology?
- It is associated with Barret’s oesophagus
- Intestinal metaplasia- Tumour produces mucins
- Tumour mutations in TP53
- It occurs in the distal colon
- Hence lymph node spread- gastric and coeliac nodes
- Usually presents after lymph node metastasis and hence poor prognosis as compared to squamous cell carcinoma
Investigations for Oesophageal adenocarcinoma
Endoscopy
Biopsy
Oesophageal squamous cell carcinoma
- Oesophageal squamous-cell carcinomas may occur as ______ ________tumors associated with _____ and ______ cancer, due to field cancerization
- Primary oesophageal cancer however is more commonly an _________
- Anal cancers are normally ________ _______ ________
- Oesophageal squamous-cell carcinomas may occur as second primary tumors associated with head and neck cancer, due to field cancerization
- Primary oesophageal cancer however is more commonly an adenocarcinoma
- Anal cancers are normally squamous cell carcinomas
Adenocarcinoma
- Stomach is lined by ______ ________ normally
- Risk factors for cancer = ________, diet, __ ______ ______
- Two types of gastric adenocarcinoma: _______ vs _______
- Intestinal type forms glands (polypoid)
- Stomach is lined by glandular epithelium normally
- Risk factors for cancer = smoking, diet, H pylori infection
- Two types of gastric adenocarcinoma: Intestinal vs Diffuse type
- Intestinal type forms glands (polypoid)
Epidemiology of squamous cell carcionoma
Male > female (4:1)
More seen in the African American population
Epidemiology of Oesophageal Adenocarcinoma?
Male > female (7:1)
More seen in the Caucasian population
What is Crohn’s disease?
Inflammation that can involve one small area of the gut, or multiple areas with normal bowel in between: SKIP LESIONS
AKA Cobblestone appearance
Commonly affects the terminal ileum and ascending colon- resulting in RLQ pain
Transmural Inflammation: Damage extends beyond the submucosal layer and through the depth of the entire intestinal wall (unlike UC)
micro organisms related to Crohns
Mycobacterium paratuberculosis as well Pseudomonas and Listeria species
Complications of Crohns
fistulae, abscess, bowel obstruction, perforation, toxic megacolon, kidney stones, Bowel cancer (adenocarcinoma), gallstones
Patho fo UC
AUTOIMMUNE Th2 mediated rxn, where cytotoxic T cells target abnormal gut bacteria or p-ANCA antibodies, thus eroding the lining of the intestines, and ulceration
The circumferential inflammation can destroy the haustras of the colon leading to a smooth section of colon which is called the “lead pipe” sign.
Prevalent in non-smokers/ex-smokers*
Classifications of UC
- Proctitis: Just the rectum
- Proctosigmoiditis: Involves the rectum and sigmoid colon
- Left sided Colitis: Involves the descending colon up to the splenic flexure
- Extensive Colitis: Extending to the hepatic flexure
- Pancolitis/Universal colitis: The entire colon is affected, associated with Backwash Ileatis (inflammation of the terminal ileum)
Difference between Crohns and UC
What is Diverticulitis?
Inflammation of abnormal pouches called diverticula (can develop on the walls of the large intestine, or any other hollow structure). Usually 0.5c,-1cm large
True Diverticula: involve all layers of the intestine
Pseudo diverticula: Muscle layers are not included MOST COMMON
When abdominal outpouching occurs without inflammation, it is called ________
diverticulosis
Risk factors for Diverticulitis?
Obesity, lack of exercise, low fibre diet, Smoking, Connective tissue disorders (genetic), Family history, NSAIDs, Common in the western world, Elderly, Females
Symptoms of Diverticulitis?
Symptoms: MOST CASES ARE ASYMPTOMATIC
- Lower abdominal pain (sudden onset)- mostly affects the Sigmoid colon- LLQ pain and tenderness
- Erratic bowel habits
- Symptoms of infection (fever, tachycardia), Nausea, Diarrhea, Constipation, Fever, blood/mucus in the stool
Investigations and Treatment for Diverticulitis?
Raised CRP and ESR, USS, CT, Barium enema, Sigmoidoscopy
Treatment
If less severe: analgesia, Fibre, Antibiotics, Fluid resus
Surgical resection if acutely unwell
What is Coeliac’s disease?
An AUTOIMMUNE DISORDER where exposure to gluten causes an autoimmune reaction that causes inflammation in the small bowel. It usually develops in early childhood but can start at any age.
1 in 100 people have it. Family History increases risk to 1 in 10.
Pathophysiology of Coeliac’s Disease
Gluten is a large molecule, that is broken down to smaller ones in the gut, and it is the breakdown products that are toxic (gliadins). The main toxic peptide is α-Gliadin.
Autoantibodies are created in response to exposure to gluten, which target the epithelial cells of the intestines, leading to inflammation in the small bowel (particularly jejunum)
It causes atrophy of the intestinal villi, and crypt hypertrophy, so the surface of the bowel becomes flattened, and the surface area for absorption becomes greatly reduced (malabsorption)
Important antibodies to know for coeliac disease?
- Anti-TTG (anti-tissue transglutaminase)- attacks TTG, which is responsible for gluten breakdown
- Anti-EMA (Anti-endomysial)
- DGP (deaminated gliadin peptide)
Clinical features of Coeliac Disease
Often asymptomatic (can be mistaken for IBS), Steatorrhea, failure to lose/gain weight, abdo pain, cramps, bloating, distension, diarrhoea, fatigue, mouth ulcers, anaemia, dermatitis herpetiformis, osteomalacia, Vit D and calcium deficiency, neurological (ataxia, epilepsy)
Coeliac disease diagnosis?
Check for total IgA levels whilst on gluten diet
- Raised Anti-TTG antibodies serology (FIRST LINE)
- Raised anti-endomysial antibodies
- deaminated gliadin peptide (DGP) – in cases of patients who have a IgA deficiency
Duodenal Biopsy to confirm
Genetic testing for HLADQ2 and HLADQ8
What is IBS?
- Irritable bowel syndrome (IBS) is a group of symptoms—including abdominal pain and changes in the pattern of bowel movements without any evidence of underlying damage (like inflammation, ulcers etc).
- It has been classified into four main types depending on whether diarrhoea is common, constipation is common, both are common, or neither occurs very often
IBD vs IBS?
IBD has structural damage to the bowel (ie inflammation, ulceration) in ADDITION to IBS symptoms
Diagnosis of IBS
What is the criteria used called
Other pathology should be excluded:
- Normal FBC, ESR and CRP blood tests
- Faecal calprotectin negative to exclude inflammatory bowel disease
- Negative coeliac disease serology (anti-TTG antibodies)
- Cancer is not suspected or excluded if suspected
Symptoms should suggest IBS:
Abdominal pain / discomfort pain for ≥12wks which has 2 of:
- Relieved by defecation
- Change in stool frequency (D or C)
- Change in stool form: pellets, mucu
AND 2 of:
- Abnormal stool passage: incomplete/urgency
- Bloating/Distention
- Worse symptoms after eating
- PR mucus
ROME CRITERIA
Risk factors for IBS
Female, stress, gastroenteritis (nota/rotavirus)
Treatment for IBS?
- A low FODMAPS diet:
F- fermentable
O- oligosaccharides 🡪 sucrose (Wheat, rye, legumes and various fruits and vegetables, such as garlic and onions.)
D- disaccharides 🡪 lactose (Milk, yogurt and soft cheese)
M- monosaccharides 🡪 fructose (Various fruit including figs and mangoes, and sweeteners such as honey
Andmitriptyline
P- polyols 🡪 sugar free sweeteners ( Certain fruits and vegetables including blackberries and lychee, as well as some low-calorie sweeteners like those in sugar-free gum.)
- Avoid caffeine and alcohol
- Probiotics, regular small meals, reduced processed food, physical activity, for constipation: soluble fibres, laxatives, stool softeners, for pain: anti-diarrhoeals (ie loperamide), antimuscarinics, antispasmodics (mebeverine)
- Manage stress, anxiety and depression- CBT
- Amitriptyline
Genetic connections with coeliac disease
Genetic connections:
HLA-DQ2 gene (90%)
HLA-DQ8 gene
What are Gallstones?
Incidence?
RF?
Symptoms
Formation of hard stones in the gallbladder
Incidence increases with age. More common in women.
F – Fat
F – Fair
F – Female
F – Forty
Most are asymptomatic and are discovered when they cause biliary colic etc
What are the types of gallstones?
- Cholesterol gallstones are the most common stones -supersaturation of bile with cholesterol –Gallbladder stasis -cannot been seen on X-RAY . However if they have enough CaCO3
- Bilirubin gallstones are the 2nd most common stones: AKA pigmented
- can be seen on X-RAY as the bilirubin binds to calcium
–associated with : hemolytic disease, E.coli
What if the stones are brown in colour?
- sign of infection (caused by bacteria Ecoli)
- causes calcium + UBC
- browness is due to hydrolysed phospholipid too in it.
What is biliary colic? and where would you find pain?
Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic (sudden pain) occurs due to a gallstone temporarily blocking the cystic duct.
- Intermittent RUQ pain that comes in waves
- Pain MAY radiate to R shoulder tip
- Typically starts in the evening and lasts till the morning
- Recurring condition, usually managed with diet adjustment
What is Cholecystitis? and where would you find pain?
- Inflammation of the cystic duct due to gallstone obstruction
- Prolonged colicky pain which MAY radiate to the shoulder tip
- Inflammation->Fever + leucocytosis
- Murphy’s Sign. There will be RUQ pain that is usually worse on inspiration.
What is Choledocholithiasis? where would you get pain?
- Common bile duct obstruction
- No inflammation -> no fever or leucocytosis
- Obstructive jaundice
- Dilated hepatic ducts
- RUQ pain> 6h
What is Cholangitis? where would you get pain?
Infection of the gallbladder and CBD
Charcot triad-> fever, jaundice and RUQ pain
Reynolds triangle -> hypotension (shock) +altered mental status + Charcoat triangle. This occurs when the infection becomes more advanced
RUQ pain
Murphy sign
Complications of gallstones?
- Cholecystitis , Acute cholangitis + Mirizzi syndrome
- Empyema +perforation
- Jaundice -> obstructive jaundice
- Acute pancreatitis -> epigastric pain, radiates to the back , curling makes it better
- Cancer of the gallbladder
- Gallstone ileus
A bowel obstruction requires immediate medical treatment. If it’s not treated, there’s a risk that the bowel could split open (rupture).
What is PRIMARY SCLEROSING CHOLANGITIS
Primary (not caused by something else)
Sclerosing (hardening/fibrosis of tissue)
Cholangitis (inflammation of bile ducts)
Disorder caused due to the chronic inflammation of the intra hepatic and extra hepatic bile ducts leading to fibrosis
More commonly occurs in males (around 30-50 years)
Causes of PRIMARY SCLEROSING CHOLANGITIS
The exact cause is unknown but it has a strong association with autoimmune disesases, especially inflammatory bowel disease (most commonly UC).
In most patients, there is presence of antibodies such as pANCA and ANA antibodies but these are not specific for the disease.
It is linked to HLA DR3 and HLA B8
Associated diseases for PRIMARY SCLEROSING CHOLANGITIS
UC
Crohn’s (much rarer)
AIH
HIV
Sclerosing Cholangitis vs Biliary Cirrhosis
WHat is PRIMARY BILIARY CHOLANGITIS?
Disorder caused due to the chronic inflammation of the intra hepatic bile ducts leading to fibrosis
More commonly occurs in females (around 30-65 years)
Presentation of PRIMARY BILIARY CHOLANGITIS
Think of PPBBCCS
- Often asympto and Dx incidentally (↑ALP)
- Jaundice occurs late
- Pruritus and fatigue
- Pigmentation of face
- Bones: osteoporosis, osteomalacia (↓vit D)
- Big organs: HSM
- Cirrhosis and coagulopathy (↓vit K)
- Cholesterol↑: xanthelasma, xanthomata
- Steatorrhoe
What is appendicitis?
causes?
Inflammation of the appendix
Can occur at any age but most commonly in the elderly or in the 2nd decade of life.
It is due to the obstruction of the appendix lumen by hyperplasia of the lymphoid tissue, feces, worms, foreign body etc.
Patho of appendicitis?
Once the lumen is obstructed, it can lead to bacterial overgrowth, ischemia, inflammation etc.
If untreated, it can lead to necrosis, peritonitis, gangrene, perforation etc
Pain in Appendicitis?
Visceral pain
n the early stages, the pain will be poorly localized to the periumbilical or epigastric region. This is because the organ is poorly innervated by the lesser splanchnic nerves which localise the pain to the centre of the abdomen.
Pain in Appendicitis?
Somatic pain
In the later stages, as the inflammation becomes worse, it spreads to the parietal peritoneum in that area, so the pain can be localized. This is because the peritoneum is supplied by the same nerve as the respective dermatome.
So, initial pain will be in the periumbilical region and then will localize to the RIF as the inflammation becomes worse
How is the pain in appendicitis described?
It is described as constant and sharp
What is Mcburney’s point?
2/3’s of the way along an imaginary line from the umbilicus to the anterior superior iliac spine on the right hand side
What is Rovsing’s Sign?
pain felt in the LRQ when the LLQ is palpated
Psoas sign –
increased pain during passive extension of the right hip
Obturator sign
pain felt on passive internal rotation of the flexed hip
what does Washboard ridgidity
This shows that there is peritonitis. the pain is exacerbated by the slightest movement (e.g. rolling, coughing, even breathing) as this moves the peritoneum.
Characteristics fo autoimmune hepatitis?
- Increased IgG levels
- Antibodies against:
Liver specific proteins
Non-live specific proteins
Mononuclear infiltrate within the liver:
Monocytes, macrophages, lymphocytes, plasma cells, macrophages and mast cells
Key definitions relating to gallbladder and gallstones?
- Cholestasis
- Cholelithiasis:
- Choledocholithiasis:
- Biliary colic:
- Cholecystitis:
- Cholangitis:
- Gallbladder empyema:
- Cholecystectomy:
- Cholecystostomy:
- Cholestasis: blockage to the flow of bile
- Cholelithiasis: gallstone(s) are present
- Choledocholithiasis: gallstone(s) in the bile duct
- Biliary colic: intermittent right upper quadrant pain caused by gallstones irritating bile ducts
- Cholecystitis: inflammation of the gallbladder
- Cholangitis: inflammation of the bile ducts
- Gallbladder empyema: pus in the gallbladder
- Cholecystectomy: surgical removal of the gallbladder
- Cholecystostomy: inserting a drain into the gallbladder
atients with gallstones and biliary colic are advised to avoid fatty foods to prevent CCK release and gallbladder contraction.
TRUE OR FALSE
TURE
Ix for gallstones
LFTs- raised bilirubin, ALP
USS- first line
In a raised ALT and AST with higher rise in ALP , this suggest?
cholestasis an”obstructive picture”
If ALT and AST are high compared with the ALP level, this is more indicative of…
a problem inside the liver with hepatocellular injury “a hepatitic picture”
A raised ALP is consistent with ______ ___________ in presence of right upper quadrant pain and/or jaundice.
A raised ALP is consistent with biliary obstruction in presence of right upper quadrant pain and/or jaundice.
What is (MRCP)
A magnetic resonance cholangio-pancreatography (MRCP) is an MRI scan with a specific protocol that produces a detailed image of the biliary system. It is very sensitive and specific for biliary tree disease, such as stones in the bile duct and malignancy.
MRCP is used in a number of scenarios for gaining a detailed picture of the biliary system, such as identifying biliary strictures or congenital abnormalities.
With gallstone disease, MRCP is typically used to investigate further if the ultrasound scan does not show stones in the duct, but there is bile duct dilatation or raised bilirubin suggestive of obstruction.
What is ERCP
Complications
An endoscopic retrograde cholangio-pancreatography (ERCP) involves inserting an endoscope down the oesophagus, past the stomach, to the duodenum and the opening of the common bile duct (the sphincter of Oddi). This gives the operator access to the biliary system.
The main indication for ERCP is to clear stones in the bile ducts.
Key complications of ERCP are:
- Excessive bleeding
- Cholangitis (infection in the bile ducts)
- Pancreatitis
Complications of cholecystectomy include:
- Bleeding, infection, pain and scars
- Damage to the bile duct including leakage and strictures
- Stones left in the bile duct
- Damage to the bowel, blood vessels or other organs
- Anaesthetic risks
- Venous thromboembolism (deep vein thrombosis or pulmonary embolism)
- Post-cholecystectomy syndrome
What is Post-cholecystectomy syndrome
Post-cholecystectomy syndrome involves a group of non-specific symptoms that can occur after a cholecystectomy. They may be attributed to changes in the bile flow after removal of the gallbladder. Symptoms often improve with time. Symptoms include:
- Diarrhoea
- Indigestion
- Epigastric or right upper quadrant pain and discomfort
- Nausea
- Intolerance of fatty foods
- Flatulence
What is Wilson Disease?
How is it inherited?
What gene and what chromosome?
Wilson disease is the excessive accumulation of copper in the body and tissues. It is caused by a mutation in the “Wilson disease protein” on chromosome 13. The Wilson disease protein also has the catchy name “ATP7B copper-binding protein” and is responsible for various functions, including the removal of excess copper in the liver. Genetic inheritance is autosomal recessive.
Clinical Features of Wilson disease?
think of CLANKAH
Cornea
- Kayser-Fleischer rings (70%, may need slit-lamp)
Liver Disease
- Children usually present c̄acute hepatitis.
- Fulminant necrosis may occur
- →cirrhosis
Arthritis
- Chondrocalcinosis
- Osteoporosis
Neurology
- Parkinsonism:bradykinesia,tremor, chorea, tics
- Spasticity, dysarthria, dysphagia
- Ataxia
- Depression, dementia, psychosis
Kidney
- Fanconi’s syn. (T2 RTA)→osteomalacia
Abortions
Haemolytic anaemia
- Coombs’ negative
Copper deposition in the liver leads to ____ _____ and eventually liver cirrhosis. Copper deposition in the ______ _____ ______ can lead to neurological and psychiatric problems.
Copper deposition in the liver leads to chronic hepatitis and eventually liver cirrhosis. Copper deposition in the central nervous system can lead to neurological and psychiatric problems.
Ix of Wilson Disease?
- Bloods:↓Cu,↓caeruloplasmin
NB. Caeruloplasmin is an acute-phase protein and maybe high during infection. It may also be low protein-deficient states: nephroticsyndrome, malabsorption
- ↑24h urinary Cu
- Liver biopsy:↑hepatic Cu
- MRI:basal-ganglia degeneration
Management for wilsons disease
Treatment is with copper chelation using:
- Penicillamine (lifelong)
- Trientene
eating typically worsens the pain of ______ ulcers and improves the pain of _________ ulcers.
eating typically worsens the pain of gastric ulcers and improves the pain of duodenal ulcers.
Management for peptic ulcer?
Peptic ulcers are diagnosed by endoscopy. During endoscopy a rapid urease test (CLO test) can be performed to check for H. pylori. Biopsy should be considered during endoscopy to exclude malignancy as cancers can look similar to ulcers during the procedure.
Medical treatment is the same as with GORD, usually with high dose proton pump inhibitors. Endoscopy can be used to monitoring the ulcer to ensure it heals and to assess for further ulcers
First, Second and Third line Medication for IBS
First Line Medication:
- Loperamide for diarrhoea
- Laxatives for constipation. Avoid lactulose as it can cause bloating. Linaclotide is a specialist laxative for patients with IBS not responding to first-line laxatives
- Antispasmodics for cramps e.g. hyoscine butylbromide (Buscopan)
Second Line Medication:
- Tricyclic antidepressants (i.e. amitriptyline 5-10mg at night)
Third Line Medication:
- SSRIs antidepressants
What is hiatus hernia
A hiatus hernia is when part of your stomach moves up into your chest. It’s very common if you’re over 50. It does not normally need treatment if it’s not causing you problems
Explain the classification of Hiatus Hernia?
Sliding (80%)
- Gastro-oesophageal junction slides up into chest
- Often assoc. c̄GORD
Rolling (15%)
- Gastro-oesophageal junction remains in abdomen but abulge of stomach rolls into chest alongside theoesophagus
- LOS remains intact so GORD uncommon
- Can→strangulation
Mixed (5%)
Ix for Hiatus Hernia
- CXR:gas bubble and fluid level in chest
- Ba swallow: diagnostic
- OGD: visualises the mucosa but can’t exclude hernia
- 24h pH + manometry:exclude dysmotility or achalsia
Tx for Hiatus Hernia
- Lose wt.
- Rx reflux
- Surgery if intractable symptoms despite medical Rx.-Should repair rolling hernia (even if asympto) as it may strangulate
What is hereditary haemochromatosis
How is it inherited
What gene on what chromonsome:
Hereditary hemochromatosis (he-moe-kroe-muh-TOE-sis) causes your body to absorb too much iron from the food you eat. Excess iron is stored in your organs, especially your liver, heart and pancreas. Too much iron can lead to life-threatening conditions, such as liver disease, heart problems and diabetes
AR
HFE gene (High FE) on Chr6 (C282Y
Patho haemochromatosis
- Inherited, multisystem disorder resulting from abnormaliron metabolism.
- ↑intestinal Fe absorption (↑enterocyte DMT +↓hepatocyte hepcidin)→deposition in multiple organ
Clinical features of Haemochromotosis
Myocardial
- Dilated cardiomyopathy
- Arrhythmias
Endocrine
- Pancreas: DM
- Pituitary: hypogonadism→amenorrhoea, infertility
- Parathyroid: hypocalcaemia, osteoporosis
Arthritis
- 2ndand 3rdMCP joints, knees and shoulders
Liver
- Chronic liver disease→cirrhosis→HCC
- Hepatomegaly
Skin
- Slate grey discolouration
Ix of Haemochromatosis
- Bloods:↑LFT,↑ferritin,↑Fe,↓TIBC, glucose, genotype
- X-ray:chondrocalcinosis
- ECG, ECHO
- Liver biopsy:Pearl’s stain to quantify Fe and severity
- MRI:can estimate iron loading
Treatment for haemochromotosis
Iron removal
- Venesection: aim for Hct <0.5
- Desferrioxamine is 2ndline
General
- Monitor DM
- Low Fe diet
Screening
- Se ferritin and genotype
- Screen 1stdegree relatives
Transplant in cirrhosis
Patho of Wilson’s Disease
- Mutation of Cu transporting ATPase
- Impaired hepatocyte incorporation of Cu intocaeruloplasmin and excretion into bile.
- Cu accumulation in liver and, later, other organ
Symptoms and signs of PSC
Symptoms
- Jaundice
- Pruritus and fatigue
- Abdo pain
Signs
- Jaundice: dark urine, pale stools
- HSM
Complications of PSC
Bacterial cholangitis
↑Cholangiocarcinoma
↑CRC
Ix for PSC
- LFTs:↑ALP initially, then↑BR
- Abs:pANCA (80%), ANA and SMA may be +ve
- ERCP/MRCP:“beaded” appearance of ducts
- Biopsy:fibrous, obliterative cholangitis
Associated diseased with primary bilary cirrhosis ?
rimary biliary cholangitis is associated with metabolic or immune system disorders, including thyroid problems, limited scleroderma (CREST syndrome), rheumatoid arthritis, and dry eyes and mouth (Sjogren’s syndrome)
What are the types of Liver function tests?
ALT- Markers of hepatocellular damage, localised to liver
AST- Markers of hepatocellular damage, synthesised by liver, heart, skeletal muscle and brain
Billirubin- Assessing degree of jaundice
gGT- Cholestasis
ALP- Cholestasis – sources are bone and liver
Albumin- Synthetic function
Prothrombin time - Synthetic function
Liver function tests- imaging
- USS- Ultrasound is usually first line. Identifies any obstructive pathology present or gross liver pathology
- Fibroscan
- MRI
- MRCP- Used to visualise the biliary tree. Usually performed if obstructive jaundice is suspected or US is inconclusive
- X rays – hepatic angiogram
- CT
- Biopsy- Performed when the diagnosis has not been made despite the above investigations
What is Jaundice?
yellow appearance of the skin, sclerae and mucous membranes resulting from an increased bilirubin concentrations in body fluids
What are the types of jaundice?
- Pre-hepatic
- Hepatic/ intrahepatic/ hepatocellular
- Post-hepatic
Pre-hepatic jaundice and also be called?
haemolytic jaundice
What is pre hepatic jaundice?
Excessive red cell breakdown which overwhelms the liver’s ability to conjugate bilirubin 🡪 unconjugated hyperbilirubinemia
Any bilirubin that manages to become conjugated is excreted normally
Unconjugated bilirubin in the blood causes jaundice
ALT, AST, ALP will be normal
Examples of conditons that can see pre hepatic jaundice?
- Examples
- Haemolytic anaemia
- Malaria
- Sickle cell thalassemia
- SLE
What is hepatic jaundice?
- Due to dysfunction of the hepatic cells
- Liver loses the ability to conjugate bilirubin
- Liver may become cirrhotic 🡪 compromises the intra-hepatic portions of the biliary tree to cause some obstruction
- Both unconjugated and conjugated bilirubin are found in blood
- High ALT, AST and ALP (higher ALT&AST)
Examples of conditions where you can hepatic jaundice?
- Alcoholic liver disease
- Viral hepatitis
- Primary biliary cirrhosis
- Hepatocellular carcinoma
What is Post-hepatic jaundice
- AKA obstructive jaundice
- Due to obstruction of biliary drainage
- Bilirubin that has been conjugated by the liver is not excreted
- Excess conjugated bilirubin = conjugated hyperbilirubinemia
- High ALP, AST and ALT (higher ALP)
What is Acute liver failure?
Onset of hepatic decompensation within 6 months, results in loss of function in 80-90%
Causes of Acute Liver failure?
- Drugs
50% of cases in the UK due to paracetamol overdose
others inc NSAIDs and ecstasy
- Infection
Viral hepatitis, CMV, HSV, EBV
- Acute fatty liver in pregnancy
Unmetabolized fetal fatty acids enter maternal circulation and accumulate in mothers liver
- Wilsons disease
AR, copper accumulates in the liver
- Budd-Chiari
Occlusion of hepatic vein
Abdo pain + ascites + liver enlargement
Clinical features of Acute liver failure?
- Jaundice
- Bruising (coagulation disturbance)
- Ascites
- Tachycardia and hypotension
- Due to reduced systemic vascular resistance
- Signs of encephalopathy
- Sweet smell on breath
Complications of acute liver failure
- Hepatic encephalopathy = altered level of consciousness
- Impaired protein synthesis = measured by serum albumin + prothrombin time in blood
What is Chronic liver failure
Progressive destruction/regeneration of liver parenchyma leading to fibrosis and cirrhosis (> 6 months
Causes of chronic liver failure
- Metabolic
Hereditary haemochromatosis -Accumulation of iron, reacts with H2O2 to form free radicals
NAFLD
Wilsons disease
- Toxic and drugs
Alcohol
Drug induced is rare 🡪 methotrexate, amiodarone
- Infections – hep b & c
- Autoimmune
Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis
Clinical features of Chronic liver failure?
- Nail clubbing
- Palmar erythema
- Spider nevi
- Gynaecomastia
- Feminising hair distribution
- Small irregular shrunken liver
- Anaemia
- Caput medusae
Complications of chronic liver failure?
- Portal hypertension
- Synthetic dysfunction
- Hepatopulmonary syndrome
- Hepatorenal syndrome
- Encephalopathy
- Hepatocellular carcinoma
What is portal hypertension?
- Increased blood pressure in the hepatic portal system (portal venous system) usually due to hepatic cirrhosis
- Obstruction may prevent the blood flow from the portal vein into the IVC
- Causes the blood to accumulate in the hepatic portal system 🡪 increasing the pressure 🡪 PORTAL HYPERTENSION
- Portosystemic Shunts- anastomoses between portal and systemic systems, due to portal HTN the blood backs up and varices form- these can rupture
- Features (ABCDE)- ascites, bleeding, caput medusae, diminished liver function and enlarged spleen
What is hepatic encephalopathy?
Reduced blood to liver 🡪 reduced liver function
Increased ammonia crosses BBB
Can be gradual or sudden
In advanced stages 🡪 coma
Clinical features of heaptic encephalopathy
Asterixis, lethargy, movement problems, changes in mood or changes in personality, altered consciousness, seizures
What is treatment for hepatic encephalopathy?
Treatment = Oral lactulose
What is Hepatopulmonary syndrome
Syndrome of shortness of breath and hypoxemia caused by vasodilation in lungs of patients with liver disease
Causes of hepatopulmonary syndrome?
Due to formation of microscopic intrapulmonary arteriovenous dilations
Thought to be due to increased liver production or decreased liver clearance of vasodilators, e.g. NO
Dilation of blood vessels 🡪 over-perfusion relative to ventilation 🡪 V/Q mismatch
Increased gradient between the partial pressure of O2 in alveoli and adjacent arteries
What is Hepatorenal syndrome?
Life-threatening medical condition that consists of rapid deterioration of kidney function in individuals with cirrhosis or fulminant liver failure
Occurs due to portal hypertension
What is HEpatocellular carcinoma
Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis
Most common type of primary liver cancer
Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis
Most common type of primary liver cancer
What is the adenoma- carcinoma sequence?
A stepwise pattern; of mutational activation of oncogenes ( ie Kras) and inactivation of tumour suppressor genes (eg p53) that results in cancer
Environmental factors that leads to GI cancer development
- Smoking
- Alcohol
- Diet; processed meat ( especially red meat), increased obesity risk, green vegetables and diet high in fibre protective against colorectal cancer
- Chronic inflammation ie patients with ulcerative colitis have increased risk of developing colorectal cancer
- Upper GI cancer; H pylori infection?
Hallmarks of cancer
Hallmarks of cancer
Environmental factors that leads to GI cancer development
- Smoking
- Alcohol
- Diet; processed meat ( especially red meat), increased obesity risk, green vegetables and diet high in fibre protective against colorectal cancer
- Chronic inflammation ie patients with ulcerative colitis have increased risk of developing colorectal cancer
- Upper GI cancer; H pylori infection?
what is Colorectal cancer development in relation to TSG and Oncogenes
- Inactiviation of APC
- Activation of Kras
- Inactivation of p53
what is Colorectal carcinogenisis in IBD development in relation to TSG and Oncogenes?
Same genes different order
- P53
- Kras
- APC
what is Colorectal carcinogenisis in IBD development in relation to TSG and Oncogenes?
Same genes different order
- P53
- Kras
- APC
what is Colorectal cancer development in relation to TSG and Oncogenes
- Inactiviation of APC
- Activation of Kras
- Inactivation of p53
APC KRA and P53
which of these are tumour supressor genes?
APC and P53
APC KRas and P53
Which of these are oncgenes?
KRas
APC KRas and P53
Which of these are oncgenes?
KRas
APC KRA and P53
which of these are tumour supressor genes?
APC and P53
Typical upper GI cancer would be
Oesophageal cancers
Gastric cancers
Typical lower GI cancer would be
colorectal cancers
Difference between HNPCC and FAP
Difference between HNPCC and FAP
Pathology of Colorectal Cancer
Most common : adenocarcinoma ( a malignant tumour formed from glandular structures of the epithelial tissue)
Less common; mucinous adenocarcinoma, signet ring cell carcinoma, small cell carcinoma
Glandular dysplasia is the premalignant lesion, when it forms a poly it is commonly referred to as an adenoma
Adenomas classified as tubular, tubulovillous and villous (the is the worst one)
Adenomas are also graded in terms of dysplasia (low or high)
Staging using TNM for Corectal Cancers
Tumour staging
Staging using TNM for Corectal Cancers
Lymph nodes staging
Staging using TNM for Corectal Cancers
Metastasis staging
Staging using TNM for Corectal Cancers
Metastasis staging
Pathology of gastric cancers?
Pathology of gastric cancers?
Staging using TNM for Corectal Cancers
Lymph nodes staging
Staging using TNM for Corectal Cancers
Tumour staging
Pathology of Colorectal Cancer
Most common : adenocarcinoma ( a malignant tumour formed from glandular structures of the epithelial tissue)
Less common; mucinous adenocarcinoma, signet ring cell carcinoma, small cell carcinoma
Glandular dysplasia is the premalignant lesion, when it forms a poly it is commonly referred to as an adenoma
Adenomas classified as tubular, tubulovillous and villous (the is the worst one)
Adenomas are also graded in terms of dysplasia (low or high)
What are the causes of acute pancreatitis?
Gallstones - Obstruct sphincter of Oddi causing reflux . Bile salts irritates pancreatic duct
Ethanol - Increases acinar cell secretion, decreases ductal cell secretion → thickened pancreatic juice . ROS damages the cells
Trauma - Usually ruptured duct in the body of the pancreas from direct trauma (vertebral column)
Drugs - sodium valporate, furosemide, thiazides, Azathioprine
What are the causes of acute pancreatitis?
Gallstones - Obstruct sphincter of Oddi causing reflux . Bile salts irritates pancreatic duct
Ethanol - Increases acinar cell secretion, decreases ductal cell secretion → thickened pancreatic juice . ROS damages the cells
Trauma - Usually ruptured duct in the body of the pancreas from direct trauma (vertebral column)
Drugs - sodium valporate, furosemide, thiazides, Azathioprine
Colorectal cancer is the __ most commone cancer in the UK
Most occur in the ___
___ most common cause of cancer death in the UK
4th
rectum
2nd
Risk factors of colorectal cancer?
family history, those that have FAP or HNPCC, diet with lack of fibre, inflammatory bowel disease (ie ulcerative colitis)
What are familial adenomatous polyposis?
Classic familial adenomatous polyposis, called FAP or classic FAP, is a genetic condition. It is diagnosed when a person develops more than 100 adenomatous colon polyps. An adenomatous polyp is an area where normal cells that line the inside of a person’s colon form a mass on the inside of the intestinal trac
How are Familial adenomatous polyposis inherited?
Autosomal dominant inheritance
How is HNPCC (hereditary non polyposis colon cancer) inhertied?
Autosomal dominant inheritance
HNPCC (hereditary non polyposis colon cancer)
Mutations occur where
Mutations in the DNA mismatch repair genes (MSH2 (60%)) and MLH1 (30%)), causing microsatellite instability. These genes normally maintain stability of DNA during replication
HNPCC (hereditary non polyposis colon cancer)
Mutations occur where
Mutations in the DNA mismatch repair genes (MSH2 (60%)) and MLH1 (30%)), causing microsatellite instability. These genes normally maintain stability of DNA during replication
RED FLAG symptoms for colorectal cancer?
- Unintentional / unexplained weight loss
- Rectal bleeding
- Change in bowel habit
- Abdominal masses
- Iron deficiency anaemia
- In history; ask about family history- family members with ovarian and bowel cancer can be significan
RED FLAG symptoms for colorectal cancer?
- Unintentional / unexplained weight loss
- Rectal bleeding
- Change in bowel habit
- Abdominal masses
- Iron deficiency anaemia
- In history; ask about family history- family members with ovarian and bowel cancer can be significan
How is HNPCC (hereditary non polyposis colon cancer) inhertied?
Autosomal dominant inheritance
How are Familial adenomatous polyposis inherited?
Autosomal dominant inheritance
What are familial adenomatous polyposis?
Classic familial adenomatous polyposis, called FAP or classic FAP, is a genetic condition. It is diagnosed when a person develops more than 100 adenomatous colon polyps. An adenomatous polyp is an area where normal cells that line the inside of a person’s colon form a mass on the inside of the intestinal trac
If a tumour that invades the muscularis propria, metastasizes to 1-3 lymph nodes but does has no distant metastasis how would you use TNM?
T2N1M0
If a tumour that invades the muscularis propria, metastasizes to 1-3 lymph nodes but does has no distant metastasis how would you use TNM?
T2N1M0
Gastric cancer clinical features
Epigastric pain; may be relieved by food and antacids
Dysphagia especially if tumour involves stomach fundus
Anaemia
Nausea, vomiting and weight loss
Can have Liver, bone , brain and lung involvement
What is Zollinger- Ellison syndrome?
Zollinger–Ellison syndrome is a disease in which tumours cause the stomach to produce too much acid, resulting in peptic ulcers. A gastrin secreting tumour (gastrinoma) - Excess gastric acid secretion leads to (unusual/severe peptic ulceration, oesophagitis, diarrhoea and
WHat are gastrinomas?
- Neuroendocrine tumours
- Gastrin secreting
- Cause severe peptic ulcer disease and diarrhoea (referred to as the Zollinger Ellison Syndrome)
- Can either be sporadic (75-80% of cases) or associated with Multiple endocrine neoplasia type 1 (20-30% of cases)
What is acute pancreatitis?
Sudden inflammation, haemorrhage of pancreas due to autodigestion from inappropriate activation of zymogen (trypsinogen → trypsin)
Reversible
What is acute pancreatitis?
Sudden inflammation, haemorrhage of pancreas due to autodigestion from inappropriate activation of zymogen (trypsinogen → trypsin)
Reversible
Investiagtions for acute pancreatitis?
Elevated serum amylase >1000 IU/L
Elevated serum lipase (2-5x normal value)
LFTs: gallstones aetiology (jaundice)
Imaging
CT: swollen gland with inflammation, necrosis, pseudocyst
USS: gallstones
What is chronic pancreatitis?
- Chronic inflammation causing irreversible structural damage
Atrophy of acinar cells
Fibrosis
Calcification
Dilation of ducts/ narrowing
- Formation of chronic pseudocysts, intrapancreatic cysts
What is pathogenesis of Chronic pancreatitis?
Obstruction in the pancreatic ducts
Ductal dilatation and damage to tissue (atrophy of acinar cells)
Stellate cells lay down fibrotic tissue
Further resulting in atrophy of acinar cells, intraluminal calcification, narrowing of ducts
Causes of chronic pancreatitis?
- Recurrent episodes of acute pancreatitis (alcohol)
- Duct obstruction: tumour, gallstones, structural abnormalities (annular pancreas, pancreas divisum), traumatic strictures
- Cystic fibrosis
Investiagtions for chronic pancreatitis?
Serum lipase and amylase may or may not be elevated
Glucose tolerance test (endocrine function)
Imaging
CT : calcification, intrapancreatic cysts or chronic pseudocysts
ERCP: dilated and strictured ducts (chain of lakes pattern)
To differentiate from carcinoma
Pancreatic imaging + EUS + targeted needle biopsy
Complications of chronic pancreatitis?
Increased risk of pancreatic carcinoma
Pancreatic pseudocysts, fistula, ascites
Biliary obstruction
Malnutrition
Diabetes mellitus
Risk factors for Pancreatic carcinoma
Western lifestyle
Cigarette smoking
High-fat diet
Liver cirrhosis
Chronic pancreatitis
Obesity
Family history/genetic factors (BRCA1/BRCA2/FAP/HNPCC)
Name some congenital anomalies
Hirschprung’s Disease
Meckel’s Diverticulum
Omphalocele
Gastroschisis
What is Hirschprung’s Disease
Agangliosis of myenteric and submucosal plexus in the distal colon and rectum which causes lack of peristalsis
Functional obstruction from spasms in denervated colon
Severe constipation within first 2 months
Investigations
X ray: colon distension
Biopsy to identify transition zone
Management: surgical removal of affected segment
What is Meckel’s Diverticulum?
Persistence of vitellointestinal duct
Rule of 2s
2% of population
Present in first 2 years
2 inches in length
Approximately 2 ft from ileocaecal valve
What is Omphalocele?
Herniation of intestines (sometimes liver and other organs) out of umbilicus at birth due to abdominal wall defects
Failure to return to abdomen after natural protrusion during development
Covered by peritoneal membrane and amnion
Investigations: USS antenatal scan shows herniated loop contained within peritoneum
Associated with severe malformations, 25% mortality
What is Gastroschisis?
Herniation of bowel loops (sometimes stomach and liver) through para-umbilical wall defect (lateral to the umbilicus)
Not covered by surrounding membrane
Investigations: Antenatal USS show herniation to lateral of umbilicus, free-floating
What is alcoholic liver disease?
Alcoholic liver disease results from the effects of the long term excessive consumption of alcohol on the liver. The onset and progression of alcoholic liver disease varies between people, suggesting that there may be a genetic predisposition to having harmful effects of alcohol on the liver.
What are the 3 stepwise pricess of progression of alcoholic liver disease?
1. Alcohol related fatty liver
Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks.
2. Alcoholic hepatitis
Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.
3. Cirrhosis
This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
What is the recommended alcohol consumption
That latest recommendations (Department of Health, 2016) are to not regularly drink more than 14 units per week for both men and women.
If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day.
The government guidelines also state that any level of alcohol consumption increases the risk of cancers, particularly breast, mouth and throat.
Pregnant women should avoid alcohol completely.
What is AUDIT Questionnaire
The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organisation to screen people for harmful alcohol use. It involves 10 questions with multiple choice answers and gives a score. A score of 8 or more gives an indication of harmful use.
Complications of Alcohol
- Alcoholic Liver Disease
- Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma
- Alcohol Dependence and Withdrawal
- Wernicke-Korsakoff Syndrome (WKS)
- Pancreatitis
- Alcoholic Cardiomyopathy
Signs of Liver Disease
- Jaundice
- Hepatomegaly
- Spider Naevi
- Palmar Erythema
- Gynaecomastia
- Bruising – due to abnormal clotting
- Ascites
- Caput Medusae – engorged superficial epigastric veins
- Asterixis – “flapping tremor” in decompensated liver disease
Ix for Alcohol Liver Disease
Bloods
FBC – raised MCV
LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis.
Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver
U+Es may be deranged in hepatorenal syndrome.
Ultrasound
An ultrasound of the liver may show fatty changes early on described as “increased echogenicity”. It can also demonstrate changes related to cirrhosis if present.
“FibroScan” can be used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis.
Endoscopy
Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected.
CT and MRI scans
CT and MRI can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.
Liver Biopsy
Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis. NICE recommend considering a liver biopsy in patients where steroid treatment is being considered.
What is general management for alcohol liver disease
- Stop drinking alcohol permanently
- Consider a detoxication regime
- Nutritional support with vitamins (particularly thiamine) and a high protein diet
- Steroids improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term
- Treat complications of cirrhosis (portal hypertension, varices, ascites and hepatic encephalopathy)
- Referral for liver transplant in severe disease however they must abstain from alcohol for 3 months prior to referral
Withdrawal symptoms
Symptoms occur at different times after alcohol consumption ceases:
- 6-12 hours:
- 12-24 hours:
- 24-48 hours:
- 24-72 hours:
- 6-12 hours: tremor, sweating, headache, craving and anxiety
- 12-24 hours: hallucinations
- 24-48 hours: seizures
- 24-72 hours: “delirium tremens”
What is Delirium Tremens
Delirium tremens is a medical emergency associated with alcohol withdrawal with a mortality of 35% if left untreated. Alcohol stimulates GABA receptors in the brain. GABA receptors have a “relaxing” effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors) having a further inhibitory effect on the electrical activity of the brain.
When alcohol is removed from the system, GABA under-functions and glutamate over-functions causing an extreme excitability of the brain with excess adrenergic activity. This presents as:
- Acute confusion
- Severe agitation
- Delusions and hallucinations
- Tremor
- Tachycardia
- Hypertension
- Hyperthermia
- Ataxia (difficulties with coordinated movements)
- Arrhythmias
What is CIWA-Ar
(Clinical Institute Withdrawal Assessment – Alcohol revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.
Which benzodiazepine is used to combat the effects of alcohol withdrawal.
What is alternative?
Chlordiazepoxide (“Librium”)
Diazepam
Wernicke-Korsakoff Syndrome (WKS)
What is it?
Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency.
What are the Features of Wernicke’s encephalopathy
- Confusion
- Oculomotor disturbances (disturbances of eye movements)
- Ataxia (difficulties with coordinated movements)
What are the Features of Korsakoffs syndrome
- Memory impairment (retrograde and anterograde)
- Behavioural changes
*
Korsakoffs syndrome reversible or irreversible
What is NAFLD?
What is the extreme form of this called ?
Non alcholic fatty liver disease (NAFLD) forms part of the “metabolic syndrome” group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes. It is estimated that up to 30% of adults have NAFLD. It is characterised by fat deposited in liver cells. These fat deposits can interfered with the functioning of the liver cells. NAFLD does not cause problems initially, however it can progress to hepatitis and cirrhosis.
Non-alcoholic steatohepatitis (NASH) is most extremeform and→cirrhosis in 10%
NAFLD stages?
- Non-alcoholic Fatty Liver Disease
- Non-Alcoholic Steatohepatitis (NASH)
- Fibrosis
- Cirrhosis
NAFLD Risk factors
- Obesity
- Poor diet and low activity levels
- Type 2 diabetes
- High cholesterol
- Middle age onwards
- Smoking
- High blood pressure
Investigation in Non-Alcoholic Fatty Liver Disease
Liver Ultrasound can confirm the diagnosis of hepatic steatosis (fatty liver). It does not indicate the severity, the function of the liver or whether there is liver fibrosis.
Enhanced Liver Fibrosis (ELF) blood test. This is the first line recommended investigation for assessing fibrosis but it is not currently available in many areas. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates the fibrosis of the liver:
- < 7.7 indicates none to mild fibrosis
- ≥ 7.7 to 9.8 indicates moderate fibrosis
- ≥ 9.8 indicates severe fibrosis
NAFLD fibrosis score is the second line recommended assessment for liver fibrosis where the ELF test is not available. It is based on an algorithm of age, BMI, liver enzymes, platelets, albumin and diabetes and is helpful in ruling out fibrosis but not assessing the severity when present.
Fibroscan is the third line investigation. It involves a particular ultrasound that measures the stiffness of the liver and gives an indication of fibrosis. This is performed if the ELF blood test or NAFLD fibrosis score indicates fibrosis.
- BMI
- Glucose, fasting lipids
- ↑transaminases: AST:ALT <
- Liver biopsy
Management NAFLD
- Weight loss
- Exercise
- Stop smoking
- Control of diabetes, blood pressure and cholesterol
- Avoid alcohol
Refer patients with liver fibrosis to a liver specialist where they may treat with vitamin E or pioglitazone.
What is liver cirrhosis?
Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver.
This fibrosis affects the structure and blood flow through the liver, which causes increased resistance in the vessels leading in to the liver. This is called ________ __________
portal hypertension
4 most common causes of Liver cirrhosis
- Alcoholic liver disease
- Non Alcoholic Fatty Liver Disease
- Hepatitis B
- Hepatitis C
Rarer Causes of cirrhosis?
- Genetic:Wilson’s,α1ATD, HH, CF
- AI:AH, PBC, PSC
- Drugs:Methotrexate, amiodarone, methyldopa,INH
- Neoplasm:HCC, mets
- Vasc:Budd-Chiari, RHF,constrict. pericarditis
Signs of Cirrhosis
What do they suggest?
Hands
- Clubbing (± periostitis)
- Leuconychia (↓albumin)
- Terry’s nails (white proximally, red distally)
- Palmer erythema- caused by hyperdynamic cirulation
- Dupuytron’s contracture
- Asterixis – “flapping tremor” in decompensated liver diseas
Face
- Pallor: ACD
- Xanthelasma: PBC
- Parotid enlargement (esp. c̄EtOH)
- Jaundice – caused by raised bilirubin
Trunk
- Spider naevi (>5, fill from centre)- these are telangiectasia with a central arteriole and small vessels radiating away
- Gynaecomastia- in males due to endocrine dysfunction
- Loss of sexual hair
- Brusing- due to abnormal clotting
Abdo
- Striae
- Hepatomegaly (may be small in late disease)
- Splenomegaly- due to portal hypertension
- Caput Medusae – distended paraumbilical veins due to portal hypertension
- Testicular atrophy- in males due to endocrine dysfunction
Ix for liver cirrhosis?
Bloods
- FBC:↓WCC and↓plats indicate hypersplenism
- ↑LFTs
- ↑INR
- ↓Albumin
Find Cause
- EtOH:↑MCV,↑GGTNASH:hyperlipidaemia,↑glucose
- Infection:Hep, CMV, EBV serology
- Genetic:Ferritin,α1AT, caeruloplasmin (↓in Wilson’s)
- Autoimmune:Abs (there is lots of cross-over)
- AIH:SMA, SLA, LKM, ANA
- PBC:AMA
- PSC:ANCA, ANA
- Ig:↑IgG – AIH,↑IgM – PBC
- Ca:α-fetoprotein
Abdo US + PV Duplex
- Small / large liver
- Focal lesions
- Reversed portal vein flow
- Ascites
Ascitic Tap + MCS
PMN >250mm3indicates SBP
Liver biopsy
Majority of pancreatic cancers are?
adenocarcinomas
Name some drug induced Jaundice
Name some drug induced Jaundice
Pancreatic Cancer
Pre hepatic/hepatic/Post hepatic
Post Hepatic
Obstructive jaundice
Where does pancreatic cancers spread to usually?
liver, then to the peritoneum, lungs and bones.
Viral Hepatitis
There are types A-E
explain how they are spread and their cause
Viral Hepatitis
There are types A-E
explain how they are spread and their cause
Presentation of pancreatic cancer?
- Painless Obstructive jaundice
- Yellow skin and sclera
- Pale stools
- Dark urine
- Generalised itching
- Non-specific upper abdominal or back pain
- Unintentional weight loss
- Palpable mass in the epigastric region
- Change in bowel habit
- Nausea or vomiting
- New‑onset diabetes or worsening of type 2 diabetes
It is worth noting that a new onset of diabetes, or a rapid worsening of glycaemic control type 2 diabetes, can be a sign of __________ ______
Pancreatic cancer
What are the NICE guidelines for when to refer for suspected pancreatic cancer:
- Over 40 with jaundice – referred on a 2 week wait referral
- Over 60 with weight loss plus an additional symptom (see below) – referred for a direct access CT abdomen
When does GP directly refer to accesss CT abdomen to assess pancreatic cancer?
if a patient has weight loss plus any of:
- Diarrhoea
- Back pain
- Abdominal pain
- Nausea
- Vomiting
- Constipation
- New‑onset diabetes
What is the sign called for palpable gallbladder along with jaundice
Courvoisier’s law
suggests cholangiocarcinoma or pancreatic cancer
What is Trousseau’s sign of malignancy
refers to migratory thrombophlebitis as a sign of malignancy, particularly pancreatic adenocarcinoma. Thrombophlebitis is where blood vessels become inflamed with an associated blood clot (thrombus) in that area. Migratory refers to the thrombophlebitis reoccurring in different locations over time.
Ix for pancreatic cancer?
Diagnosis is based on imaging (usually CT scan) plus histology from a biopsy.
Staging CT scan involves a full CT thorax, abdomen and pelvis (CT TAP). This is used to look for metastasis and other cancers.
CA 19-9 (carbohydrate antigen) is a tumour marker that may be raised in pancreatic cancer.
Magnetic resonance cholangio-pancreatography (MRCP) may be used to assess the biliary system in detail to assess the obstruction.
Endoscopic retrograde cholangio-pancreatography (ERCP) can be used to put a stent in and relieve the obstruction, and also obtain a biopsy from the tumour.
Biopsy may be taken through the skin (percutaneous) under ultrasound or CT guidance, or during an endoscopy under ultrasound guidance.
Management for pancreatic cancer
Surgery
- Total pancreatectomy
- Distal pancreatectomy
- Pylorus-preserving pancreaticoduodenectomy (PPPD) (modified Whipple procedure)
- Radical pancreaticoduodenectomy (Whipple procedure)
In most cases, curative surgery is not possible. Palliative treatment may involve:
- Stents inserted to relieve the biliary obstruction
- Surgery to improve symptoms (e.g., bypassing the biliary obstruction)
- Palliative chemotherapy (to improve symptoms and extend life)
- Palliative radiotherapy (to improve symptoms and extend life)
- End of life care with symptom control
What is Whipple Procedure?
A Whipple procedure (pancreaticoduodenectomy) is a surgical operation to remove a tumour of the head of the pancreas that has not spread. A Whipple procedure is a massive operation so patients need to be in good baseline health.
Whipple Procedure involves the removal of ?
- Head of the pancreas
- Pylorus of the stomach
- Duodenum
- Gallbladder
- Bile duct
- Relevant lymph nodes
A modified Whipple procedure is called
pylorus-preserving pancreaticoduodenectomy (PPPD).
leave pylorus in place
Symptoms of Meckels’ Divertculum
Symptoms
- GI bleeding (May contain gastric mucosa → gastric ulcerations)
- Abdominal pain and cramping
- Tenderness near the belly button
- Obstruction of bowels
Causes of pre-hepatic jaundice
Excess (billirubin) BR production
- Haemolytic anaemia
- Ineffective erythropoiesise.g. thalassaemia
Causes of unconjugated hepatic jaundice
↓BR Uptake
- Drugs: contrast, RMP
- CCF
↓BR Conjugation
- Hypothyroidism
- Gilbert’s (AD)
- Crigler-Najjar (AR)
Neonatal jaundice is both ↑production +↓conju
Causes of conjugated hepatic jaundice
Hepatocellular Dysfunction
- Congen:HH, Wilson’s,α1ATD
- Infection:Hep A/B/C, CMV, EBV
- Toxin:EtOH, drugs
- AI:AIH
- Neoplasia:HCC, mets
- Vasc:Budd-Chiari
↓Hepatic BR Excretion
- Dubin-Johnson
- Rotor’
Causes of post hepatic jaundice
Obstruction
- Stones
- Ca pancreas
- Drugs
- PBC
- PSC
- Biliary atresia
- Choledochal cyst
- Cholangio Ca
What convertes uBR to cBR
BR-UDP-glucuronyl transferase in live
what are normal billirubin levels
at what levels can jaundice obvious
- Normal BR = 3-17uM
- Jaundice visible @ 50uM (3 x ULN
what are normal billirubin levels
at what levels can jaundice obvious
- Normal BR = 3-17uM
- Jaundice visible @ 50uM (3 x ULN
What is Gilbert’s syndrome
How is it inherited?
What percentage of population is affected?
Dx:
In Gilbert’s syndrome, slightly higher than normal levels of a substance called bilirubin build up in the blood.
- Auto dom partial UDP-GT deficiency
- 2% of the population
- Jaundice occurs during intercurrent illness
- Dx:↑uBR on fasting, normal LFTs
What is Crigler-Najjar
What is treatment
- Rare auto rec total UDP-GT deficiency
- Severe neonatal jaundice and kernicterus
- Rx:liver Transplant
What grading is used for Liver Cirrhosis
Explain it
Child-Pugh Grading of Cirrhosis
- Predicts risk of bleeding, mortality and need for Tx
- Graded A-C using severity of 5 factors
- Albumin
- Bilirubin
- Clotting
- Distension: Ascites
- Encephalopathy
- Score >8 = significant risk of variceal bleeding
What grading is used for Liver Cirrhosis
Explain it
Child-Pugh Grading of Cirrhosis
- Predicts risk of bleeding, mortality and need for Tx
- Graded A-C using severity of 5 factors
- Albumin
- Bilirubin
- Clotting
- Distension: Ascites
- Encephalopathy
- Score >8 = significant risk of variceal bleeding
Patho of autoimmune hepatitis
- Inflammatory disease of unknown cause characterisedby Abs directed vs. hepatocyte surface antigens
- Predominantly young and middle-aged women
Classification of autoimmune hepatitis
Classified according to Abs
- T1:Adult, SMA+ (80%), ANA+ (10%),↑IgG
- T2:Young, LKM+
- T3:Adult, SLA+
What are some associated diseases with autoimmune hepatitis
Autoimmune thyroiditis
DM
Pernicious anaemia
PSC
UC
GN
AIHA (Coombs +ve)
Ix for autoimmune hepatitis
- ↑LFTs
- ↑IgG
- Auto Abs: SMA, LKM, SLA, ANA
- ↓WCC and↓plats = hypersplenism
- Liver biopsy
Mx for autoimmune hepatitis
Immunosuppression
- Prednisolone
- Azathioprine as steroid-sparer
Liver transplant (disease may recur)
Mx for autoimmune hepatitis
Immunosuppression
- Prednisolone
- Azathioprine as steroid-sparer
Liver transplant (disease may recur)
Ix for autoimmune hepatitis
- ↑LFTs
- ↑IgG
- Auto Abs: SMA, LKM, SLA, ANA
- ↓WCC and↓plats = hypersplenism
- Liver biopsy
What are some associated diseases with autoimmune hepatitis
Autoimmune thyroiditis
DM
Pernicious anaemia
PSC
UC
GN
AIHA (Coombs +ve)
Classification of autoimmune hepatitis
Classified according to Abs
- T1:Adult, SMA+ (80%), ANA+ (10%),↑IgG
- T2:Young, LKM+
- T3:Adult, SLA+
Patho of autoimmune hepatitis
- Inflammatory disease of unknown cause characterisedby Abs directed vs. hepatocyte surface antigens
- Predominantly young and middle-aged women
What is Crigler-Najjar
What is treatment
- Rare auto rec total UDP-GT deficiency
- Severe neonatal jaundice and kernicterus
- Rx:liver Transplant
What is Gilbert’s syndrome
How is it inherited?
What percentage of population is affected?
Dx:
In Gilbert’s syndrome, slightly higher than normal levels of a substance called bilirubin build up in the blood.
- Auto dom partial UDP-GT deficiency
- 2% of the population
- Jaundice occurs during intercurrent illness
- Dx:↑uBR on fasting, normal LFTs
What convertes uBR to cBR
BR-UDP-glucuronyl transferase in live
Causes of post hepatic jaundice
Obstruction
- Stones
- Ca pancreas
- Drugs
- PBC
- PSC
- Biliary atresia
- Choledochal cyst
- Cholangio Ca
Causes of conjugated hepatic jaundice
Hepatocellular Dysfunction
- Congen:HH, Wilson’s,α1ATD
- Infection:Hep A/B/C, CMV, EBV
- Toxin:EtOH, drugs
- AI:AIH
- Neoplasia:HCC, mets
- Vasc:Budd-Chiari
↓Hepatic BR Excretion
- Dubin-Johnson
- Rotor’
Causes of unconjugated hepatic jaundice
↓BR Uptake
- Drugs: contrast, RMP
- CCF
↓BR Conjugation
- Hypothyroidism
- Gilbert’s (AD)
- Crigler-Najjar (AR)
Neonatal jaundice is both ↑production +↓conju
Causes of pre-hepatic jaundice
Excess (billirubin) BR production
- Haemolytic anaemia
- Ineffective erythropoiesise.g. thalassaemia
Symptoms of Meckels’ Divertculum
Symptoms
- GI bleeding (May contain gastric mucosa → gastric ulcerations)
- Abdominal pain and cramping
- Tenderness near the belly button
- Obstruction of bowels
A modified Whipple procedure is called
pylorus-preserving pancreaticoduodenectomy (PPPD).
leave pylorus in place
Whipple Procedure involves the removal of ?
- Head of the pancreas
- Pylorus of the stomach
- Duodenum
- Gallbladder
- Bile duct
- Relevant lymph nodes
What is Whipple Procedure?
A Whipple procedure (pancreaticoduodenectomy) is a surgical operation to remove a tumour of the head of the pancreas that has not spread. A Whipple procedure is a massive operation so patients need to be in good baseline health.
Management for pancreatic cancer
Surgery
- Total pancreatectomy
- Distal pancreatectomy
- Pylorus-preserving pancreaticoduodenectomy (PPPD) (modified Whipple procedure)
- Radical pancreaticoduodenectomy (Whipple procedure)
In most cases, curative surgery is not possible. Palliative treatment may involve:
- Stents inserted to relieve the biliary obstruction
- Surgery to improve symptoms (e.g., bypassing the biliary obstruction)
- Palliative chemotherapy (to improve symptoms and extend life)
- Palliative radiotherapy (to improve symptoms and extend life)
- End of life care with symptom control
Ix for pancreatic cancer?
Diagnosis is based on imaging (usually CT scan) plus histology from a biopsy.
Staging CT scan involves a full CT thorax, abdomen and pelvis (CT TAP). This is used to look for metastasis and other cancers.
CA 19-9 (carbohydrate antigen) is a tumour marker that may be raised in pancreatic cancer.
Magnetic resonance cholangio-pancreatography (MRCP) may be used to assess the biliary system in detail to assess the obstruction.
Endoscopic retrograde cholangio-pancreatography (ERCP) can be used to put a stent in and relieve the obstruction, and also obtain a biopsy from the tumour.
Biopsy may be taken through the skin (percutaneous) under ultrasound or CT guidance, or during an endoscopy under ultrasound guidance.
What is Trousseau’s sign of malignancy
refers to migratory thrombophlebitis as a sign of malignancy, particularly pancreatic adenocarcinoma. Thrombophlebitis is where blood vessels become inflamed with an associated blood clot (thrombus) in that area. Migratory refers to the thrombophlebitis reoccurring in different locations over time.
What is the sign called for palpable gallbladder along with jaundice
Courvoisier’s law
suggests cholangiocarcinoma or pancreatic cancer
When does GP directly refer to accesss CT abdomen to assess pancreatic cancer?
if a patient has weight loss plus any of:
- Diarrhoea
- Back pain
- Abdominal pain
- Nausea
- Vomiting
- Constipation
- New‑onset diabetes
What are the NICE guidelines for when to refer for suspected pancreatic cancer:
- Over 40 with jaundice – referred on a 2 week wait referral
- Over 60 with weight loss plus an additional symptom (see below) – referred for a direct access CT abdomen
It is worth noting that a new onset of diabetes, or a rapid worsening of glycaemic control type 2 diabetes, can be a sign of __________ ______
Pancreatic cancer
Presentation of pancreatic cancer?
- Painless Obstructive jaundice
- Yellow skin and sclera
- Pale stools
- Dark urine
- Generalised itching
- Non-specific upper abdominal or back pain
- Unintentional weight loss
- Palpable mass in the epigastric region
- Change in bowel habit
- Nausea or vomiting
- New‑onset diabetes or worsening of type 2 diabetes
Where does pancreatic cancers spread to usually?
liver, then to the peritoneum, lungs and bones.
Pancreatic Cancer
Pre hepatic/hepatic/Post hepatic
Post Hepatic
Obstructive jaundice
Majority of pancreatic cancers are?
adenocarcinomas
Ix for liver cirrhosis?
Bloods
- FBC:↓WCC and↓plats indicate hypersplenism
- ↑LFTs
- ↑INR
- ↓Albumin
Find Cause
- EtOH:↑MCV,↑GGTNASH:hyperlipidaemia,↑glucose
- Infection:Hep, CMV, EBV serology
- Genetic:Ferritin,α1AT, caeruloplasmin (↓in Wilson’s)
- Autoimmune:Abs (there is lots of cross-over)
- AIH:SMA, SLA, LKM, ANA
- PBC:AMA
- PSC:ANCA, ANA
- Ig:↑IgG – AIH,↑IgM – PBC
- Ca:α-fetoprotein
Abdo US + PV Duplex
- Small / large liver
- Focal lesions
- Reversed portal vein flow
- Ascites
Ascitic Tap + MCS
PMN >250mm3indicates SBP
Liver biopsy
Signs of Cirrhosis
What do they suggest?
Hands
- Clubbing (± periostitis)
- Leuconychia (↓albumin)
- Terry’s nails (white proximally, red distally)
- Palmer erythema- caused by hyperdynamic cirulation
- Dupuytron’s contracture
- Asterixis – “flapping tremor” in decompensated liver diseas
Face
- Pallor: ACD
- Xanthelasma: PBC
- Parotid enlargement (esp. c̄EtOH)
- Jaundice – caused by raised bilirubin
Trunk
- Spider naevi (>5, fill from centre)- these are telangiectasia with a central arteriole and small vessels radiating away
- Gynaecomastia- in males due to endocrine dysfunction
- Loss of sexual hair
- Brusing- due to abnormal clotting
Abdo
- Striae
- Hepatomegaly (may be small in late disease)
- Splenomegaly- due to portal hypertension
- Caput Medusae – distended paraumbilical veins due to portal hypertension
- Testicular atrophy- in males due to endocrine dysfunction
Rarer Causes of cirrhosis?
- Genetic:Wilson’s,α1ATD, HH, CF
- AI:AH, PBC, PSC
- Drugs:Methotrexate, amiodarone, methyldopa,INH
- Neoplasm:HCC, mets
- Vasc:Budd-Chiari, RHF,constrict. pericarditis
4 most common causes of Liver cirrhosis
- Alcoholic liver disease
- Non Alcoholic Fatty Liver Disease
- Hepatitis B
- Hepatitis C
This fibrosis affects the structure and blood flow through the liver, which causes increased resistance in the vessels leading in to the liver. This is called ________ __________
portal hypertension
What is liver cirrhosis?
Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver.
Management NAFLD
- Weight loss
- Exercise
- Stop smoking
- Control of diabetes, blood pressure and cholesterol
- Avoid alcohol
Refer patients with liver fibrosis to a liver specialist where they may treat with vitamin E or pioglitazone.
Investigation in Non-Alcoholic Fatty Liver Disease
Liver Ultrasound can confirm the diagnosis of hepatic steatosis (fatty liver). It does not indicate the severity, the function of the liver or whether there is liver fibrosis.
Enhanced Liver Fibrosis (ELF) blood test. This is the first line recommended investigation for assessing fibrosis but it is not currently available in many areas. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates the fibrosis of the liver:
- < 7.7 indicates none to mild fibrosis
- ≥ 7.7 to 9.8 indicates moderate fibrosis
- ≥ 9.8 indicates severe fibrosis
NAFLD fibrosis score is the second line recommended assessment for liver fibrosis where the ELF test is not available. It is based on an algorithm of age, BMI, liver enzymes, platelets, albumin and diabetes and is helpful in ruling out fibrosis but not assessing the severity when present.
Fibroscan is the third line investigation. It involves a particular ultrasound that measures the stiffness of the liver and gives an indication of fibrosis. This is performed if the ELF blood test or NAFLD fibrosis score indicates fibrosis.
- BMI
- Glucose, fasting lipids
- ↑transaminases: AST:ALT <
- Liver biopsy
NAFLD Risk factors
- Obesity
- Poor diet and low activity levels
- Type 2 diabetes
- High cholesterol
- Middle age onwards
- Smoking
- High blood pressure
NAFLD stages?
- Non-alcoholic Fatty Liver Disease
- Non-Alcoholic Steatohepatitis (NASH)
- Fibrosis
- Cirrhosis
What is NAFLD?
What is the extreme form of this called ?
Non alcholic fatty liver disease (NAFLD) forms part of the “metabolic syndrome” group of chronic health conditions relating to processing and storing energy that increase risk of heart disease, stroke and diabetes. It is estimated that up to 30% of adults have NAFLD. It is characterised by fat deposited in liver cells. These fat deposits can interfered with the functioning of the liver cells. NAFLD does not cause problems initially, however it can progress to hepatitis and cirrhosis.
Non-alcoholic steatohepatitis (NASH) is most extremeform and→cirrhosis in 10%
Korsakoffs syndrome reversible or irreversible
What are the Features of Korsakoffs syndrome
- Memory impairment (retrograde and anterograde)
- Behavioural changes
*
What are the Features of Wernicke’s encephalopathy
- Confusion
- Oculomotor disturbances (disturbances of eye movements)
- Ataxia (difficulties with coordinated movements)
Wernicke-Korsakoff Syndrome (WKS)
What is it?
Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency.
Which benzodiazepine is used to combat the effects of alcohol withdrawal.
What is alternative?
Chlordiazepoxide (“Librium”)
Diazepam
What is CIWA-Ar
(Clinical Institute Withdrawal Assessment – Alcohol revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.
When alcohol is removed from the system, GABA under-functions and glutamate over-functions causing an extreme excitability of the brain with excess adrenergic activity. This presents as:
- Acute confusion
- Severe agitation
- Delusions and hallucinations
- Tremor
- Tachycardia
- Hypertension
- Hyperthermia
- Ataxia (difficulties with coordinated movements)
- Arrhythmias
What is Delirium Tremens
Delirium tremens is a medical emergency associated with alcohol withdrawal with a mortality of 35% if left untreated. Alcohol stimulates GABA receptors in the brain. GABA receptors have a “relaxing” effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors) having a further inhibitory effect on the electrical activity of the brain.
Withdrawal symptoms
Symptoms occur at different times after alcohol consumption ceases:
- 6-12 hours:
- 12-24 hours:
- 24-48 hours:
- 24-72 hours:
- 6-12 hours: tremor, sweating, headache, craving and anxiety
- 12-24 hours: hallucinations
- 24-48 hours: seizures
- 24-72 hours: “delirium tremens”
What is general management for alcohol liver disease
- Stop drinking alcohol permanently
- Consider a detoxication regime
- Nutritional support with vitamins (particularly thiamine) and a high protein diet
- Steroids improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term
- Treat complications of cirrhosis (portal hypertension, varices, ascites and hepatic encephalopathy)
- Referral for liver transplant in severe disease however they must abstain from alcohol for 3 months prior to referral
Ix for Alcohol Liver Disease
Bloods
FBC – raised MCV
LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis.
Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver
U+Es may be deranged in hepatorenal syndrome.
Ultrasound
An ultrasound of the liver may show fatty changes early on described as “increased echogenicity”. It can also demonstrate changes related to cirrhosis if present.
“FibroScan” can be used to check the elasticity of the liver by sending high frequency sound waves into the liver. It helps assess the degree of cirrhosis.
Endoscopy
Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected.
CT and MRI scans
CT and MRI can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.
Liver Biopsy
Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis. NICE recommend considering a liver biopsy in patients where steroid treatment is being considered.
Signs of Liver Disease
- Jaundice
- Hepatomegaly
- Spider Naevi
- Palmar Erythema
- Gynaecomastia
- Bruising – due to abnormal clotting
- Ascites
- Caput Medusae – engorged superficial epigastric veins
- Asterixis – “flapping tremor” in decompensated liver disease
Complications of Alcohol
- Alcoholic Liver Disease
- Cirrhosis and the complications of cirrhosis including hepatocellular carcinoma
- Alcohol Dependence and Withdrawal
- Wernicke-Korsakoff Syndrome (WKS)
- Pancreatitis
- Alcoholic Cardiomyopathy
What is AUDIT Questionnaire
The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organisation to screen people for harmful alcohol use. It involves 10 questions with multiple choice answers and gives a score. A score of 8 or more gives an indication of harmful use.
What is the recommended alcohol consumption
That latest recommendations (Department of Health, 2016) are to not regularly drink more than 14 units per week for both men and women.
If drinking 14 units in a week, this should be spread evenly over 3 or more days and not more than 5 units in a day.
The government guidelines also state that any level of alcohol consumption increases the risk of cancers, particularly breast, mouth and throat.
Pregnant women should avoid alcohol completely.
What are the 3 stepwise pricess of progression of alcoholic liver disease?
1. Alcohol related fatty liver
Drinking leads to a build-up of fat in the liver. If drinking stops this process reverses in around 2 weeks.
2. Alcoholic hepatitis
Drinking alcohol over a long period causes inflammation in the liver sites. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.
3. Cirrhosis
This is where the liver is made up of scar tissue rather than healthy liver tissue. This is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.
What is alcoholic liver disease?
Alcoholic liver disease results from the effects of the long term excessive consumption of alcohol on the liver. The onset and progression of alcoholic liver disease varies between people, suggesting that there may be a genetic predisposition to having harmful effects of alcohol on the liver.
What is Gastroschisis?
Herniation of bowel loops (sometimes stomach and liver) through para-umbilical wall defect (lateral to the umbilicus)
Not covered by surrounding membrane
Investigations: Antenatal USS show herniation to lateral of umbilicus, free-floating
What is Omphalocele?
Herniation of intestines (sometimes liver and other organs) out of umbilicus at birth due to abdominal wall defects
Failure to return to abdomen after natural protrusion during development
Covered by peritoneal membrane and amnion
Investigations: USS antenatal scan shows herniated loop contained within peritoneum
Associated with severe malformations, 25% mortality
What is Meckel’s Diverticulum?
Persistence of vitellointestinal duct
Rule of 2s
2% of population
Present in first 2 years
2 inches in length
Approximately 2 ft from ileocaecal valve
What is Hirschprung’s Disease
Agangliosis of myenteric and submucosal plexus in the distal colon and rectum which causes lack of peristalsis
Functional obstruction from spasms in denervated colon
Severe constipation within first 2 months
Investigations
X ray: colon distension
Biopsy to identify transition zone
Management: surgical removal of affected segment
Name some congenital anomalies
Hirschprung’s Disease
Meckel’s Diverticulum
Omphalocele
Gastroschisis
Risk factors for Pancreatic carcinoma
Western lifestyle
Cigarette smoking
High-fat diet
Liver cirrhosis
Chronic pancreatitis
Obesity
Family history/genetic factors (BRCA1/BRCA2/FAP/HNPCC)
Complications of chronic pancreatitis?
Increased risk of pancreatic carcinoma
Pancreatic pseudocysts, fistula, ascites
Biliary obstruction
Malnutrition
Diabetes mellitus
Investiagtions for chronic pancreatitis?
Serum lipase and amylase may or may not be elevated
Glucose tolerance test (endocrine function)
Imaging
CT : calcification, intrapancreatic cysts or chronic pseudocysts
ERCP: dilated and strictured ducts (chain of lakes pattern)
To differentiate from carcinoma
Pancreatic imaging + EUS + targeted needle biopsy
Causes of chronic pancreatitis?
- Recurrent episodes of acute pancreatitis (alcohol)
- Duct obstruction: tumour, gallstones, structural abnormalities (annular pancreas, pancreas divisum), traumatic strictures
- Cystic fibrosis
What is pathogenesis of Chronic pancreatitis?
Obstruction in the pancreatic ducts
Ductal dilatation and damage to tissue (atrophy of acinar cells)
Stellate cells lay down fibrotic tissue
Further resulting in atrophy of acinar cells, intraluminal calcification, narrowing of ducts
What is chronic pancreatitis?
- Chronic inflammation causing irreversible structural damage
Atrophy of acinar cells
Fibrosis
Calcification
Dilation of ducts/ narrowing
- Formation of chronic pseudocysts, intrapancreatic cysts
Investiagtions for acute pancreatitis?
Elevated serum amylase >1000 IU/L
Elevated serum lipase (2-5x normal value)
LFTs: gallstones aetiology (jaundice)
Imaging
CT: swollen gland with inflammation, necrosis, pseudocyst
USS: gallstones
WHat are gastrinomas?
- Neuroendocrine tumours
- Gastrin secreting
- Cause severe peptic ulcer disease and diarrhoea (referred to as the Zollinger Ellison Syndrome)
- Can either be sporadic (75-80% of cases) or associated with Multiple endocrine neoplasia type 1 (20-30% of cases)
What is Zollinger- Ellison syndrome?
Zollinger–Ellison syndrome is a disease in which tumours cause the stomach to produce too much acid, resulting in peptic ulcers. A gastrin secreting tumour (gastrinoma) - Excess gastric acid secretion leads to (unusual/severe peptic ulceration, oesophagitis, diarrhoea and
Gastric cancer clinical features
Epigastric pain; may be relieved by food and antacids
Dysphagia especially if tumour involves stomach fundus
Anaemia
Nausea, vomiting and weight loss
Can have Liver, bone , brain and lung involvement
Risk factors of colorectal cancer?
family history, those that have FAP or HNPCC, diet with lack of fibre, inflammatory bowel disease (ie ulcerative colitis)
Colorectal cancer is the __ most commone cancer in the UK
Most occur in the ___
___ most common cause of cancer death in the UK
4th
rectum
2nd
Typical lower GI cancer would be
colorectal cancers
Typical upper GI cancer would be
Oesophageal cancers
Gastric cancers
What is the adenoma- carcinoma sequence?
A stepwise pattern; of mutational activation of oncogenes ( ie Kras) and inactivation of tumour suppressor genes (eg p53) that results in cancer
What is HEpatocellular carcinoma
Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis
Most common type of primary liver cancer
Malignant tumour of the liver which occurs primarily in patients with pre-existing liver cirrhosis or chronic hepatitis
Most common type of primary liver cancer
What is Hepatorenal syndrome?
Life-threatening medical condition that consists of rapid deterioration of kidney function in individuals with cirrhosis or fulminant liver failure
Occurs due to portal hypertension
Causes of hepatopulmonary syndrome?
Due to formation of microscopic intrapulmonary arteriovenous dilations
Thought to be due to increased liver production or decreased liver clearance of vasodilators, e.g. NO
Dilation of blood vessels 🡪 over-perfusion relative to ventilation 🡪 V/Q mismatch
Increased gradient between the partial pressure of O2 in alveoli and adjacent arteries
What is Hepatopulmonary syndrome
Syndrome of shortness of breath and hypoxemia caused by vasodilation in lungs of patients with liver disease
What is treatment for hepatic encephalopathy?
Treatment = Oral lactulose
Clinical features of heaptic encephalopathy
Asterixis, lethargy, movement problems, changes in mood or changes in personality, altered consciousness, seizures
What is hepatic encephalopathy?
Reduced blood to liver 🡪 reduced liver function
Increased ammonia crosses BBB
Can be gradual or sudden
In advanced stages 🡪 coma
What is portal hypertension?
- Increased blood pressure in the hepatic portal system (portal venous system) usually due to hepatic cirrhosis
- Obstruction may prevent the blood flow from the portal vein into the IVC
- Causes the blood to accumulate in the hepatic portal system 🡪 increasing the pressure 🡪 PORTAL HYPERTENSION
- Portosystemic Shunts- anastomoses between portal and systemic systems, due to portal HTN the blood backs up and varices form- these can rupture
- Features (ABCDE)- ascites, bleeding, caput medusae, diminished liver function and enlarged spleen
Complications of chronic liver failure?
- Portal hypertension
- Synthetic dysfunction
- Hepatopulmonary syndrome
- Hepatorenal syndrome
- Encephalopathy
- Hepatocellular carcinoma
Clinical features of Chronic liver failure?
- Nail clubbing
- Palmar erythema
- Spider nevi
- Gynaecomastia
- Feminising hair distribution
- Small irregular shrunken liver
- Anaemia
- Caput medusae
Causes of chronic liver failure
- Metabolic
Hereditary haemochromatosis -Accumulation of iron, reacts with H2O2 to form free radicals
NAFLD
Wilsons disease
- Toxic and drugs
Alcohol
Drug induced is rare 🡪 methotrexate, amiodarone
- Infections – hep b & c
- Autoimmune
Primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis
What is Chronic liver failure
Progressive destruction/regeneration of liver parenchyma leading to fibrosis and cirrhosis (> 6 months
Complications of acute liver failure
- Hepatic encephalopathy = altered level of consciousness
- Impaired protein synthesis = measured by serum albumin + prothrombin time in blood
Clinical features of Acute liver failure?
- Jaundice
- Bruising (coagulation disturbance)
- Ascites
- Tachycardia and hypotension
- Due to reduced systemic vascular resistance
- Signs of encephalopathy
- Sweet smell on breath
Causes of Acute Liver failure?
- Drugs
50% of cases in the UK due to paracetamol overdose
others inc NSAIDs and ecstasy
- Infection
Viral hepatitis, CMV, HSV, EBV
- Acute fatty liver in pregnancy
Unmetabolized fetal fatty acids enter maternal circulation and accumulate in mothers liver
- Wilsons disease
AR, copper accumulates in the liver
- Budd-Chiari
Occlusion of hepatic vein
Abdo pain + ascites + liver enlargement
What is Acute liver failure?
Onset of hepatic decompensation within 6 months, results in loss of function in 80-90%
What is Post-hepatic jaundice
- AKA obstructive jaundice
- Due to obstruction of biliary drainage
- Bilirubin that has been conjugated by the liver is not excreted
- Excess conjugated bilirubin = conjugated hyperbilirubinemia
- High ALP, AST and ALT (higher ALP)
Examples of conditions where you can hepatic jaundice?
- Alcoholic liver disease
- Viral hepatitis
- Primary biliary cirrhosis
- Hepatocellular carcinoma
What is hepatic jaundice?
- Due to dysfunction of the hepatic cells
- Liver loses the ability to conjugate bilirubin
- Liver may become cirrhotic 🡪 compromises the intra-hepatic portions of the biliary tree to cause some obstruction
- Both unconjugated and conjugated bilirubin are found in blood
- High ALT, AST and ALP (higher ALT&AST)
Examples of conditons that can see pre hepatic jaundice?
- Examples
- Haemolytic anaemia
- Malaria
- Sickle cell thalassemia
- SLE
What is pre hepatic jaundice?
Excessive red cell breakdown which overwhelms the liver’s ability to conjugate bilirubin 🡪 unconjugated hyperbilirubinemia
Any bilirubin that manages to become conjugated is excreted normally
Unconjugated bilirubin in the blood causes jaundice
ALT, AST, ALP will be normal
Pre-hepatic jaundice and also be called?
haemolytic jaundice
What are the types of jaundice?
- Pre-hepatic
- Hepatic/ intrahepatic/ hepatocellular
- Post-hepatic
What is Jaundice?
yellow appearance of the skin, sclerae and mucous membranes resulting from an increased bilirubin concentrations in body fluids
Liver function tests- imaging
- USS- Ultrasound is usually first line. Identifies any obstructive pathology present or gross liver pathology
- Fibroscan
- MRI
- MRCP- Used to visualise the biliary tree. Usually performed if obstructive jaundice is suspected or US is inconclusive
- X rays – hepatic angiogram
- CT
- Biopsy- Performed when the diagnosis has not been made despite the above investigations
What are the types of Liver function tests?
ALT- Markers of hepatocellular damage, localised to liver
AST- Markers of hepatocellular damage, synthesised by liver, heart, skeletal muscle and brain
Billirubin- Assessing degree of jaundice
gGT- Cholestasis
ALP- Cholestasis – sources are bone and liver
Albumin- Synthetic function
Prothrombin time - Synthetic function
