GI Session 7 Flashcards
What are the innate physical defences against toxins?
Sight Smell Memory Saliva Gastric acid Small intestinal secretions Colonic mucus Anaerobic conditions in small bowel and colon Peristalsis and segmentation
What components of saliva allow it to be an effective defence when dealing with toxins?
Lysozymes for G+ve Lactoperoxidase for G-ve Complement IgA Polymorphs
What are the innate cellular defences against toxins in the GI tract?
Neutrophils Eosinophils Basophils Macrophages Natural killer cells
When is eosinophilia seen?
Asthma
Hay fever
Parasitic infection
What are the captive immune defences against toxin insult in the GI tract?
B lymphocytes release IgA and IgE for extracellular microbes
T lymphocytes act against intracellular microbes in MALT
What is xerostomia?
Decreased salivary flow due to severe illness and/or dehydration
How does xerostomia lead to parotitis?
S.aureus overgrowth in mouth –> dental caries –> microbes up Warton’s duct –> parotitis
What does xerostomia predispose to in the mouth?
Candida albicans (thrush) and lingua villosa nigra (black hairy tongue) due to fungal overgrowth
What defences does the oesophagus have against toxins?
Flow of liquids
Peristalsis
What defences does the stomach have against toxins?
2.5 l of gastric juice with pH as low as 0.87
Does the gastric juice in the stomach kill all bacteria and viruses?
No
What defences does the small intestine have against toxins?
Bile acting as a detergent so normally sterile Proteolytic emzymes Anaerobic environment Shedding of epithelial cells Peristalsis
What defences does the colon have against toxins?
Anaerobic environment for water recovery –> faeces 40% bacteria
Mucous layer
Why are early morning gastric washings used to diagnose TB?
M.tuberculosis is resistant to gastric acid
What viruses are resistant to gastric acid?
Enteroviruses e.g. Hep A, polio, coxsackie and norovirus
What effect does achlorhydia have on susceptibility to infection?
Increases
What can cause achlorhydia?
Pernicious anaemia
H2 antagonists
PPIs
What infections can achlorhydia lead to?
Shigellosis
Cholera
Salmonella
What causes pseudomembranous colitis in hospital pts taking PPIs?
C.diff
What can lead to loss of mucosa and other colonic defences causing overwhelming sepsis and rapid death?
Intestinal or hepatic ischaemia due to arterial disease, systemic hypotension or intestinal venous thrombosis
What toxins can the GI tract be exposed to?
Chemical Bacterial Viruses Protozoa Nematodes (roundworms) Cestodes (tapeworms) Trematodes (flukes)
What is a portal blood system?
2 capillary systems in series
What are the two capillary systems involved in the hepatic portal system?
Feedin arteriole and draining venule of a villus
Hepatic lobule capillary system
What is the purpose of the hepatic lobule capillary system?
Provides bloodflow for highly active cells surrounding bile canaliculi to transport waste materials out of hepatic sinusoids
What can cause liver failure?
Viral hepatitis Alcohol Drugs Industrial solvents Mushroom poisoning
What are the consequences of liver failure?
Increased susceptibility to infections, esp bacterial but also fungal
Increased susceptibility to toxins, drugs and hormones
Increased blood ammonia
Why do blood ammonia levels rise in liver failure?
Production by colonic bacteria and deamination of a.a. not cleared
What is cirrhosis?
Hepatic fibrosis
What are the consequences of portosystemic shunting due to portal venous hypertension?
Toxin shunting
Oesophageal Varices
Haemorrhoids
Caput medusae
What movement of veins occurs at the oesophogastric and anorectal junctions?
Cross from siting in the serosa to below mucosa
What is Caput medusa?
Pressure changes in portal venous hypertension –> bloodflow into obliterated L umbilical vein as the porta hepatis drains into it
What does the bloodflow of the tortuous veins in Caput medusa indicate?
Whether they are due to SVC obstruction, IVC obstruction or portal venous hypertension
What is Harvey’s test?
Assess cause of Caput medusa
Empty veins by applying pressure and observe refill speed: travelling upwards is faster than travelling downwards
Repeat in opposite direction to check
Where is GALT found?
Diffusely distributed and nodular in tonsils, Peyer’s patches and appendix
What are the three sets of tonsils?
Palatine
Lingual
Nasopharyngeal (adenoids)
Where do the tonsils drain?
Cervical LN associated with deep jugular vein
What is the purpose of iliocaecal lymphatic tissue?
Protect against bacterial reflux from the colon as mucosa here is not sufficient
What can cause appendicitis?
Lymphoid hyperplasia at appendix base
Faecolith
Chicken pox –> purulent appendicitis in children
What is the pathogenesis of typhoid fever?
Causes inflammation of Peyer’s patches in terminal ileum –> perforation –> death
What is the pathogenesis of mesenteric adenitis?
RIF pain in children due to adenovirus/coxsackie virus invading LN at terminal ileum
Why do chemical toxins such as metals/metaloids/solvents/drugs lead to multi organ failure?
They have developed quicker than our defences to them
Which enzyme conjugates bilirubin in the liver?
Glucuronyltransferase
Why does urobilinogen not colour urine?
It is soluble
What is prehepatic jaundice?
Excessive haemolysis and the liver cannot cope with the excess bilirubin
What can cause inherited prehepatic jaundice?
RBC membrane defects Hb abnormalities Metabolic defects Congenital hyperbilirubinaemia Gilbert's syndrome Dublin-Johnson syndrome (affected transporter protein)
What can cause acquired prehepatic jaundice?
Immune disease
Infection
Drugs
Burns
Why are the lab findings in prehepatic jaundice?
Unconjugated hyperbilirubinaemia Reticulocytosis Anaemia Increased LDH Decreased haptoglobin
What causes decreased haptoglobin in prehepatic jaundice?
Binding with Hb
What is hepatic jaundice?
Deranged hepatocytes function and swelling of hepatocytes
What are congenital causes of hepatic jaundice?
Gilbert’s or Crigler-Najjor syndromes
What are acquired causes of hepatic jaundice?
Hep viruses EBV Autoimmune disease Alcohol Haemachromatosis Wilson's disease Drugs Cirrhosis Widespread hepatic tumours
What are the lab findings in hepatic jaundice?
Mixed unconjugated/conjugated hyperbilirubinaemia
Raised AST/ALT
Normal or raised ALP
Abnormal clotting: raised INR and decreased platelets
Why might ALP be raised in hepatic jaundice?
Due to cholestasis from swollen cells
What is post-hepatic jaundice?
Intra/extrahepatic obstruction of the biliary system blocking passage of conjugate bilirubin
What can cause post-healthcare jaundice?
Intrahepatic: hepatitis, drugs, cirrhosis, primary biliary cirrhosis
Extrahepatic (distal to bile canaliculi): gallstones, biliary stricture, carcinoma, pancreatitis, sclerosing cholangitis
What are the lab findings in post-hepatic jaundice?
Conjugated hyperbilirubinaemia Dark urine Lack of urobilinogen Raised canalicular enzymes Normal or increased AST and ALT
Why is there no urobilinogen in post-hepatic jaundice?
No bilirubin in bowel so none formed
Why might AST and ALT be raised in post-hepatic jaundice?
Mild hepatocyte damage due to build up of pressure
What LFTs indicate hepatocellular damage?
Raised aminotransferases (AST and ALT) Increased gamma-glutamyl transpeptide
What LFTs indicate cholestasis?
Raised bilirubin
Raised alkaline phosphatase (ALP)
What LFTs indicate impaired synthetic function of the liver?
Decreased albumin Increased prothrombin (raised INF and decreased platelets)
What is the pathogenesis of acute/chronic hepatitis?
Virus, autoimmune, drug or herditary cause –> acute hepatocyte breakdown –> increased aminotransferases and jaundice –> decreased albumin and clotting factors
What is alpha-1-antitrypsin disease?
Autosomal recessive condition causing hepatitis and emphysema in bases of lungs
What is the Tx for hepatitis caused by alpha-1-antitrypsin deficiency?
Transplant
What is Wilson’s disease?
Autosomal recessive condition causing copper deposition in liver, basal ganglia, kidney and eyes
What is the Tx for hepatitis caused by Wilson’s disease?
Penecillamine (chelating agent)
What is the pathogenesis of alcoholic liver disease?
Alcohol consumption and probable genetic factors –> fatty change –> alcoholi helatitis –> cirrhosis
What are the consequence of alcoholic cirrhosis?
Epilepsy Hepatocellular carcinoma Liver failure Wernicke-Korsakoff syndrome Encephalopathy Cerebral atrophy --> dementia
What is the pathogenesis of liver cirrhosis?
Chronic inflammation –> liver cell necrosis –> nodular regeneration and fibrosis –> increased bloodflow resistance and deranged liver function
What is the pathogenesis of biliary cirrhosis?
Autoimmune chronic destruction of bile ducts –> jaundice, pruritis, xanthelasma and hepatosplenomegaly
What is Haemachromatosis?
Autosomal recessive condition causing deposition of iron in heart, pancreas, pituitary, liver and skin
What is the Tx haemachromatosis?
Venesection
What are the consequences of liver cirrhosis?
Spontaneous bacterial peritonitis Jaundice Anaemia Brushing Palmar erythema Dupuytren's contracture Portal hypertension
What can cause obstruction of the portal vein leading to portal hypertension?
Congenital
Thrombosis
Extrinsic compression
What can cause obstruction of bloodflow in the liver leading to portal hypertension?
Cirrhosis
Hepatoportal sclerosis
Schistosomiasis
Sarcoidosis
What are the consequences of portal hypertension?
Splenomegaly Ascites Spider naevi Caput medusa Oesophageal/rectal Varices
What causes spider naevi in portal hypertension?
Resp ducked oestrogen removal by the liver
What is fulminant hepatic failure?
An acute and/or severe decompensation of hepatic function with onset of hepatic encephalopathy within 2 months of liver disease diagnosis
What is seen in fulminant hepatic failure before supportive treatment +/- transplant?
Jaundice Encephalopathy Decreased level of consciousness Hypoglycaemia Decreased K+/Ca2+ Haemorrhage
What indicates urgent transplant in fulminant hepatic failure?
Hypoglycaemia
What can cause fulminant hepatic failure?
Hep A,D,E Drugs Reye's syndrome Alcohol Pregnancy
What is hepatic encephalopathy?
Reversible neuropsychiatric deficit caused by raised toxin levels in the blood
Why does ammonia especially cause hepatic encephalopathy?
Urea cycle function impaired –> small ammonia can pass through the BBB causing toxicity and brain swelling
What are the S/S of hepatic encephalopathy?
Flapping tremor Decreased level of consciousness Personality changes Constructional apraxia Slow, slurred speech
What can a liver failure pt experience that leads to development of hepatic encephalopathy?
Sepsis Infection Constipation Diuretic Tx Alcohol withdrawal
What are the majority of liver metastases due to?
50% from colorectal tumours metastasising via portal venous drainage
How does the incidence of primary liver tumours compare to the incidence of liver metastases?
20x more metastases
What type of benign tumour can develop in the liver?
Haemangioma
Focal nodular hyperplasia
Polycystic liver disease
How does the gallbladder change depending on how long it takes a gallstone to form?
Long time –> shrunken, fibrotic gallbladder
Short time –> large gallbladder
What can prevent passage of bile from the liver to the duodenum?
Gallstones Gallbladder structures Gallbladder atresia in neonates Infection Inflammation Neoplasia
What are the risk factors for developing cholelithiasis (gallstones)?
Female Age Obesity with rapid weight loss Diet Multiparity Ileal disease Resection --> interruption of enterohepatic circulation Haemolytic disease
What three type of gallstones can develop?
Mixed
Pure cholesterol
Pigment stones
What is the most common type of gallstone?
Mixed
What is found in mixed gallstones?
Cholesterol
Calcium
Pigment
What is the pathogenesis of biliary colic?
Impaction of stone in Hartman’s pouch –> gallbladder contraction–> post prandial pain
What is the pathogenesis of cholecystitis?
Stones –> localised oedema –> mucosa ulceration –> fibropurulent exudate –> pain, SIRS, pyrexia, sepsis
What is ascending cholangitis?
Where stone blocks common bile duct and causes inflammation proximal to blockage
What is Charcot’s triad?
RUQ pain + jaundice + fever
Indicates life threatening condition requiring urgent Abx
How do gallstones lead to biliary enteric fistula and gallstone ileus?
Fistula eroded between gallbladder and duodenum –> large stone obstructs ileum
What are 90% of pancreatic cancers?
Ductal adenocarcinoma
What are the causes of acute pancreatitis?
Gallstones Ethanol Trauma Steroids Mumps Autoimmune Scorpion bite (Trinidad) Hyperlipidaemia ERCP/iatrogenic Drugs
What happens in acute pancreatitis?
Duct obstruction --> juice and bile reflux Acinar damage --> reflux Protease--> tissue destruction Lipase--> fat necrosis Elastase--> BV destruction
What are the S/S of acute pancreatitis?
Severe pain Vomiting Dehydration Shock Ecchymosis Raised amylase, ALP, bilirubin and reduced calcium Glycaemia
What is the pathogenesis of chronic pancreatitis?
Chronic alcoholism/CF/inherited/biliary disease –> chronic inflammatory condition –> parenchymal destruction, fibrosis, loss of acini, duct stenosis
What are the S/S of chronic pancreatitis?
Pain Malabsorption--> steatorrhoea Decreased albumin Weight loss DM Jaundice
What Tx can be used in acute pancreatitis?
Supportive: ITU, fluids ?Abx
What Tx can be used in chronic pancreatitis?
Lifestyle changes
Steroids
Supportive
What is a Whipple procedure?
Surgical procedure which removes gallbladder and uses Y loop to reroute small intestine around pancreas to treat S/S of pancreatic disease
What S/S indicate use of Whipple procedure?
Palpable gallbladder Pain due to coeliac trunk compression Vomiting Carcinomatosis Malabsorption DM
