Medicine - Gastroenterology Flashcards
Describe asparate transaminase (AST)
- enzyme involved in amino acid metabolism
- not specific to liver
- raised with alcohol consumption as it is a mitochondrial enzyme and alcohol is metabolised mitochondrially
Describe alanine transaminase (ALT)
- another liver enzyme, more specific to the liver than AST
Describe gamma glutamyl transferase (GGT)
- enzyme found in many organs including the liver
- if raised it suggests:
- > obstruction
- > drugs
- > XS alcohol
Describe alkaline phosphatase (ALP)
- dephosphorylating enzyme
- found in the bile canaliculi system
- raised in:
- > bone disease
- > adolescence
- > obstructive liver disease
- > pregnancy
Describe albumin
- protein synthesised in the liver and recycled as it is needed for bilirubin movement
- a good indicator of synthetic liver function
Describe prothrombin time (PT)
- a measure of the time taken to convert prothrombin -> thrombin
- a good indicator of synthetic liver function
What would the following LFT results suggest?
- high AST, high ALT, low albumin
- hepatocellular damage (chronic) e.g. chronic hepatitis
What would the following LFT results suggest?
- high AST, high ALT, high albumin
- hepatocellular damage (acute) e.g. acute hepatitis
What would the following LFT results suggest?
- high ALP, high GGT
OBSTRUCTION
- head of pancreas cancer
PSC/PBC
What would the following LFT results suggest?
- high ALP, normal GGT
Paget’s disease/bone disease
Pregnancy
Adolescence
What would the following LFT results suggest?
- high GGT, normal ALP
AST:ALT 2:1
XS alcohol consumption (AST raised as it is a mitochondrial enzyme)
What is acute liver failure and its causes?
Development of coagulopathy & encephalopathy in a patient with a previously healthy liver
Causes:
- infection
- drugs
- toxins
- vascular (Budd-Chiara syndrome, veno-occlusive disease)
- other: PBC, PSC, cancer
What is Budd-Chiari syndrome?
occlusion of hepatic vein, presents with triad of: (HAA)
- hepatomegaly
- ascites
- abdominal pain
What are the features of acute liver failure?
jaundice fetor hepaticus asterixis hepatic encephalopathy (if underlying chronic liver disease): spider navi, synthetic dysfunction, signs of portal HTN (splenomegaly, caput medusae, ascites, pancytopenia)
What is the pathophysiology underlying hepatic encephalopathy and how is it treated?
Liver fails and waste (ammonia) builds up in the blood
Reaches the brain where glutamate is converted into glutamine to clear the waste
XS glutamine = osmotic imbalance = cerebral oedema
Treatment:
Laxatives (lose NH3)
Rifaximin (an oral antibiotic that reduces the number of nitrogen forming gut bacteria)
What investigations should be carried out for acute liver disease?
Bloods: FBC (WCC, Hb), U&E, LFT, liver autoantibodies, paracetamol levels, EtOH, glucose, coag, virology, ferritin
Microbiology: blood cultures, urine culture, ascitic tap
Imaging: USS/CXR/doppler if Bud Chiari suspected
What is spontaneous bacterial pneumonitis
Infection of ascitic fluid without an apparent source
- >250/mm3 neutrophils
Describe how SAAG is used to analyse ascites
Serum ascites albumin gradient
SAAG >1.1g/dl = transudate (failures!)
SAAG <1.1g/dl = exudate (malignancy/infection)
How is acute liver failure treated
treat the cause
Monitor for complications -> sepsis, bleeding, hypoglycaemia, varices, ascites
How is ascites treated?
Low Na diet
Diuretics
Needle drainage
Describe acute alcohol withdrawal and the pathophysiology behind it
Abrupt cessation of alcohol in pts with dependence
A clinical diagnosis
Low blood alcohol triggers AWS (alcohol withdrawal syndrome)
- can occur 12-24hrs after last drink
Pathophys:
alcohol is a GABA (inhibitory) agonist
alcohol is a NMDA receptor antagonist (stops glutamate binding to NMDA receptors)
Therefore when alcohol is removed -> lack of GABA stimulation and XS glutamate signalling = XS excitatory neurotransmission
-> autonomic hyperactivity, tremor, hallucinations, seizures
What are the features of Wernicke’s encephalopathy
Caused by thiamine deficiency (seen in alcoholics) triad of: - nystagmus - ataxia - delirium
What is korsakoffs syndrome?
chronic memory disorder due to thiamine deficiency
- severe short memory deficits and talking nonsense
What is delirium tremens
Delirium tremens (DTs) is a rapid onset of confusion usually caused by withdrawal from alcohol. When it occurs, it is often three days into the withdrawal symptoms and lasts for two to three days. Physical effects may include shaking, shivering, irregular heart rate, and sweating
How is acute alcohol withdrawal investigated
Good history
Bloods: FBC, U&E, LFT, blood ethanol
CT head
CXR -> ? aspiration
How is AWS managed
Supportive
GMAWS (guides dosing of…)
Benzodiazepines
Vitamin supplementation (pabrinex)
What questions should you ask to screen for alcohol excess?
CAGE
- are you Concerned about how much you are drinking?
- have you felt Annoyed by people criticising you/saying anything
- do you feel Guilty about drinking?
- have you ever had an Eye-opener?
Describe the pathophyiology of a paracetamol overdose
Paracetamol metabolised into a toxic compound called NAPQI -> causes cell apoptosis and liver/renal failure
Normally at therapeutic doses NAPQI is detoxified by glutathione (but in large doses glutathione is depleted)
What are the features of paracetamol overdose
24-48hrs: - Jaundice - Deranged LFTs >48hrs: - acute liver failure - hypoglycaemia - hepatic encephalopathy
How is paracetamol overdose treated?
- in first hour -> activated charcoal
- within first 4hrs: do all bloods (including paracetamol levels - these will not be accurate if measured before 4hrs)
- Use nomogram to assess risk of liver damage and if WITHIN 8hrs and high risk = IV acetyl cysteine (also called NAC parvolex)
May need to contact:
- psychiatry
- liver transplant team
What are the S/Sx of opioid overdose?
Respiratory depression
GI (vomiting, aspiration risk)
Neuro (anywhere on a scale of confused -> comatosed)
How is an opioid overdose managed?
A-E (remember CXR and ABG!)
NALOXONE! (opioid antagonist) -> 400mcg given IV/IM initially, but can increase/reduce dose is needed
What are features of hyperbilirubinaemia?
jaundice
pale fatty stools
dark urine
reduced synthesis of fat soluble vitamins (ADEK)
Name pre-hepatic causes of jaundice
XS haemolysis (malaria, yellow fever) Ineffective erythropoiesis (thalassaemia)
Name hepatic causes of jaundice
Drugs (can reduce UCBR uptake)
Issues with conjugation (Gilberts, hypothyroid, hepatitis)
Impaired CBR transport out of liver (PBC, PSC)
Name post-hepatic causes of jaundice
Obstruction
- gallstones
- HOP cancer
- pancreatitis
- PBS/PSC
- drugs
What is Gilberts disease?
AD deficiency of UDP-glucoronyl transferase enzyme (converts UCBR -> CBR)
What is a mallory-weiss tear?
Non-variceal cause of an upper GI bleed
Caused by a tear in the tissue lining the lower oesophagus
Due to increased intra-thoracic pressure (coughing, wretching, straining, vomiting)
What is Boerhaave syndrome
Seen on CXR
Pneumomediastinum
Air in the mediastinum due to transmural rupture of oesophagus
How are ruptured oesophageal varices managed?
Fluids/blood transfusion Vasoactive drugs (terlipressin) Prophylactic Abx Endoscopic therapy (banding/ligation) Sengstaken tube TIPPS
Define chronic liver disease
Development of liver failure on a background of cirrhosis
What are the features of chronic liver disease?
Jaundice encephalopathy asterixis spider navi caput medusae ascites hypersplenism pancytopenia clubbing palmar erythema leukonychia dupytrens xanthelasmas gynaecomastia hair loss
Describe budd chiari syndrome
Hepatic vein outflow obstruction Presents with triad of: - hepatomegaly - ascites - abdominal pain
How is chronic liver disease managed?
Good nutrition Vitamins Avoid alcohol 6 monthly USS and APF measurements May think about liver transplant
Describe cirrhosis and its features
Irreversible liver damage Histologicaly: - nodular regeneration - bridging fibrosis - normal hepatic architecture
Name causes of cirrhosis
Alcohol Viral (HBV, HCV) Genetic disorders (Wilsons, HHC) NAFLD Autoimmune (PSC, PBC) Drugs (amiodarone, methotrexate)
What is the eradication treatment for H.pylori
Triple therapy for 7 weeks
1) PPI
2) antibiotic (clarithromycin)
3) antibiotic (amoxicillin)
(use metronidazole for (3) if pen allergic)
Define coeliac disease and its pathophysiology
Gluten sensitive enteropathy
Inappropriate t cell response to gluten causing SI villous atrophy
Normally, IgA binds to the gluten component a-gliadin in the bowel so that it is targeted by immune cells and destroyed, but in coeliac disease the a-gliadin-IgA complex enters the lamina propria, TTG removes and amino acid from a-gliadin making it gliadin
Then, a pro-inflammatory response is created against gliadin = disease!
At a histological level what are the features of coeliac disease?
Patchy mucosal inflammation
Increased plasma cells and lymphocytes
Loss of villous height + crypt hypertrophy (so overall intestinal thickness remains the same)
Reduced SA and absorptive capacity of the bowel
What are the signs and symptoms of coeliac disease
Diarrhoea, flatulence Weight loss Fatigue Aphthous ulcers Angular stomatitis Nutritional deficiencies Anaemia (reduced Fe absorption) OP Amenorrhoea Neurological e.g. epilepsy Functional hyposplenism
How is coeliac disease investigated?
Bloods: FBC, WCC, Hb, ferritin/B12 (reduced absorption), anti-TTG antibodies
Duodenal biopsies = take 4 biopsies before GFD commenced, which may show:
- increased lymphocytes
- villous atrophy
- crypt hyperplasia
What criteria is used to grade coeliac disease?
MARSH, look at:
- villi
- crypts
- no. of intraepithelial lymphocytes per 100 enterocytes
What are the complications of coeliac disease
EATL
Refractory coeliac disease = persistent malabsorptive symptoms despite GFD for 6-12 months
Type 1 = normal immunophenotype, type 2 = abnormal immunophenotype
Define irritable bowel syndrome and its aetiology
Mixed group of abdominal symptoms for which an organic cause cannot be found
?disrupted gut-brain axis = disordered intestinal motility and enhanced visceral perception
?microbial dysbiosis
What are its symptoms and how is IBS diagnosed?
bloating mucous urgency incomplete evacuation Diagnose if pt has recurrent abdominal pain with >2 of: - relief by defecation - altered stool form - altered bowel habit
(usually exacerbated by stress, menstruation, or post-infection)
Describe the symptoms of a patient presenting with carcinoid tumour and what this tumour secretes?
FAB-D Facial flushing Abdominal cramps Bronchoconstriction (wheeze) Diarrhoea
Due to neuroendocrine tumour secreting 5-HT (serotonin)
How is a carcinoid tumour investigated and treated?
Urine - look for hormone products (5-HIAA)
USS/CT-guided tumour biopsy needed to confirm diagnosis
ECHO - check for cardiac involvement
Treatment -> resection is the only cure
What complication can occur when a carcinoid tumour is removed and what should you do to avoid this?
Carcinoid crisis -> sudden surge of hormone release
Give a somatostatin analogue (octreotide) to counteract this
Describe the King’s criteria for a possible liver transplant
- High Lactate / pH <7.3
- High INR (or PT >100 seconds)
- High creatinine >300umol/L
- Grade 3/4 encephalopathy
