List the categories of toxins that may be encoutered in the GI tract
Nematodes, Cestodes, Trematodes
What methods of defense are used aginst these toxins?
What are the innate phyiscal defenses protecting the GI tract?
Small intestine secretions
Colonic mucus peristalsis/Segmentation
What is the effect of slowed peristalsis on a gut infection?
Course of disease is prolonged (E.g. Shigellosis)
How is saliva protective against infection?
Contains Lysosyme, lactoperoxidase, complement, IgA and polymorphs
Washes toxins into the stomach (acid)
What effect can severe dehydration have on salivary defense?
Lead to microbial overgrowth in the mouth and dental caries
Caused by staph aureus
Describe the functions of the stomach as they relate to innate protection of the gut
Stomach acid works to digest food, but also to sterilise it
The 2.5L of gastric juice per day can have a pH as low as 0.87, killing all but a few bacteria and viruses
What might reduce the protective effect of stomach acid?
What is the effect of this?
Pts who have achlorhydria (Lack of stomach acid) due to anaemia, H2 antagonists and PPIs
This increases susceptibility to Shigellosis, cholera, salmonella and C. difficle infections
Give examples of bacteria and viruses resistant to stomach acid
Hep A, Polio, Coxsackie
List the protective mechanisms of the small intestine
Lack of nutrients
Shedding of epithelial cells
Rapid transit (Peristalsis)
What is the normal bacterial load in the small intestine?
What are the main protective mechanisms of the colon
Why are the important?
Mucus layer covering epithelium
Faeces are 40% bacteria by weight and so the colon wall must be isolated from this
What are the cells involved in the innate cellular defense of the GI tract?
Tissue mast cells
What is the role of eosinophils in the gut and their clinical importance?
Act against worms
Eosinophilia may indicate parasiste infection
What conditions may also produce eosinophilia?
Asthma and Hayfever
What is the clinical relevance of mast cells in the GI tract?
Gut infections may activate complement, recruiting Mast cells
Mast cells degranulate and release histamine, increasing capillary permeability
This can lead to massive fluid loss
In the case of cholera, up to 1L/hour
60% mortality untreated
What are two clinical signs of cholera?
Rapid fluid loss
What is the definition of a 'portal system'?
Give an example
Two capillary systems in series
Hepatic portal system
What are the two capillary systems linked in the hepatic portal system?
Villus capillaries along the gut wall
System of capillaries suppliying the hepatic lobules
Blood flow is from villus to lobule via the portal vein and other intermediate veins
List some examples of causes of liver failure
Drugs (Paracetamol, halothane)
Describe the effects of liver failure on the GI tract
Increased susceptiblity to infection
Toxins, drugs, hormones:
Ammonia produced by colonic bacteria may not be cleared due to failure of the urea cycle
Hepatic encephalopathy may result
Describe the effects of cirrhosis
Leads to reductions in liver function (liver failure)
Also portal hypertension (>20mmHg)
Portal hypertension leads to shunting of blood into systemic circulation (therefore toxins are also shunted)
- Oesophageal varices
- Caput medusae
Describe fully the symptoms of Porto-systemic shunting in liver cirrhosis
Highly vascular 'cushions' in the anal canal become swollen due to increased venous pressure
Venous dilation in the lower third of the oesophagus due to increased venous pressure
Engorged para-umbilical veins visible on the peri- umbilical skin due to increased venous pressure
Portal anstomoses with retroperitoneal veins cused capillary leakage into peritoneum
Congestion due to portal hypertension
Small spiderwebs of swollen veins on the skin surface, found in the areas drained by the SVC only
What are the cellular adaptive defenses releavant to the GI tract?
Production of antibodies (IgE, IgA) for defense against extracellular microbes
Defense against intracellular organisms
Describe the distribution of lymphatic tissue in the GI tract
Gut associated lymphoid tissue is diffusely distributed throughout the gut and surrounding tissues (E.g. Mesentery)
Also nodular in 3 locations:
- Peyer's Patches
Describe the drainage of the tonsils and the clincial relevance of this
Drain into cervical lymph nodes in the neck
Sore throats and cervical lymphadenopathy are a common presentation due to bacteria/viruses entering the body through the mouth
What are Peyer's patches?
Major clincal relevance?
Nodular GALT in the mucosa of the terminal ileum
Infection and subsequent inflammation of Peyer's patches in typhoid fever can cause perforation of the terminal ileum, which can be rapidly fatal
What is mesenteric adenitis?
Inflammation of lymph nodes along the mesentery
Common cause of right iliac fossa pain in children, can be mistaken for appendicitis
Often caused by adenovirus/coxsackie virus
What is Appendicitis?
Appendix obstruction leads to fluid stasis within the lumen
Infection results and the appendix becomes inflammed
What are the common causes of appendicitis?
What are some of the complications of appendicitis?
Strangulation leading to ischaemia and necrosis
Rupture of the appendix can lead to peritonitis and septicaemia
Why is hepatic/intestinal ischaemia so harmful?
GI tract relies on intact blood supply for successful defense
Ischaemia commonly leads to overwhelming sepsis and death within hours
What are the functions of the liver?
Carbohydrate, protein and lipid metabolism
Vit D snythesis
Vitamin and mineral storage
What are the common liver function tests?
Wat are they testing for?
Tests for hepatocellular damage:
Serum ALT/AST (aminotransferases)
Serum g-GT (gamma-glutamyl transpeptidase)
Tests for cholestasis (bile duct obstruction):
Serum Alkaline phosphatase
Tests for Synthetic functions:
Prothrombin time (clotting)
Describe the presentation and classification of jaundice
Yellow pigmentation in eyes and skin
- Prehepatic (Haemolytic)
- Hepatic (parenchymal)
- Post-hepatic (Cholestatic)
What is the cause of prehepatic jaundice?
How is this determined to be occuring clinically?
Liver unable to cope with excess bilirubin
What are some of the causes of prehepatic jaundice?
Acquired membrane defects
What is hepatocellular junadice and how is jaundice determined to be hepatocellular in nature?
Deranged hepatocyte function
Element of cholestasis
Mixed conjugated and unconjugated hyperbilirubinaemia
Increased liver enzymes
Abnormal clotting (increased prothrombin time)
What are some causes of hepatocellular jaundice?
Viruses (Hep A, B, C, E + EBV)
What is post-hepatic jaundice and how might jaundice be determine to be post hepatic in nature?
Obstruction of the billary system
Passage of conjugated bilirubin therefore blocked
Bilirubin in urine
Increased serum liver enzymes
What are the common causes of post-hepatic jaundice?
Carcinoma (E.g. in head of pancreas or Ampulla of vater)
What is Courvoisier's law?
Explain the rationale
In the presence of a non-tender, palpable gallbladder, painless juandice is unlikelt to be caused by gallstones
Gallstones formed over a long period of time result in a shrunken, fibrotic gallbladder (not palpable)
Palpable enlarged gallbladder normally caused by more rapid billary obstruction (E.g. Malignancy)
Acute cholecystisitis often causes a tender and distended gallbladder (Distended with mucocele or empyema
What are the acute/chronic effects of hepatiti?
AST/ALT release from hepatocytes
Reduced albumin and clotting factors
Increased prothrombin time
List some causes of hepatitis
Hep A, B, C
Isoniazid (TB treatment)
Describe the pathological prgoression in aloholic liver disease
What are some complications?
Steatosis (fatty change)
Briefly describe liver cirrhosis
Liver cell necrosis followed by nodular regeneration and fibrosis
Results in increased resistance to blood flow and deranged liver function
What are the common causes of cirrhosis?
Hep B or C
What are the clinical features of cirrhosis?
Dupuytren's contracture (fixed flexion deformity of the fingers)
Spontaneous bacteria peritonitis
What are the haematological signs of cirrhosis?
Raised Alkaline phosphatase
Increased prothrombin time
What are the management methods for cirrhosis?
Treatment of complications
Describe the cause, clinical signs and treatment of primary billary cirrhosis
Chronic destruction of bile ducts
Supportive treatment and transplantation
What is hereditary haemochromotosis?
What diseases may occur as a result?
Autosomal dominant disease:
Abnormal iron transport and deposition
What is Wilson's disease?
What can result?
How is it treated?
Disordered copper transport and deposition
Kidney tubular degneration
Penecillamine (chelation therapy)
What is A1-antitrypsin deficiency?
What can it cause?
How is it treated?
What are the causes of portal hypertension?
Obstruction of portal vein:
Obstruction of flow within the liver:
Where does the hepatic portal system anastomose with the systemic circulation?
Link this to the symptoms of portal hypertension
Oesophageal branch of left gastric vein (portal) anastomose with the Oesophageal tributaries of azygous system (systemic)
Superior rectal branch of IMV (portal) anastomoses with the inferior rectal veins (systemic)
Portal veins in liver anastomose with ant. abd. wall veins
Portal tributaries of mesentery and retroperitoneal veins
What can be the complications of Oesophageal varices?
Rupture of the swollen vessels or ulceration
Haemorrhage can potentially be significant
What is fulminant hepatic failure?
Acute/Severe onset decompensation of liver function defined as:
Onset of hepatic encephalopathy within 2 months of diagnosis of liver disease which may be linked to brain oedema
Decompensation is due to increased metabolic demand
What are the causes of fulminant hepatic failure?
Hep A, D, E
What are the clinical featuers of fulminant hepatic encephalopathy?
How is it managed?
Loss of consiousness
Supportive therapy and transplant
What is hepatic encephalopathy and what might precipitate it?
Reversible neuropsychiatric deficit
Inability to remove toxins from blood (Ammonia)
What are the clinical features of hepatic encephalopathy?
Loss of conciousness
Intellectual deterioration (Constructional apraxia, slow, slurred speech)
Give examples of benign and malignant liver tumours
Focal nodular hyperplasia
Polycystic liver disease
Primary hepatocellular carcinoma
Secondary metastases (20x more common):
- Colorectal (50%)
What are the pathological processes which can affect the billary tree?
How common are gallstones and what are the risk factors?
10 - 20% of population
What are the different types of stones that cause cholelithiasis?
Cholesterol with Ca2+ and bile pigment
Multiple small stones
What are the common clincal consequences of gallstone formation?
Impaction of stone
Gallbladder contraction (in attempt to clear)
Stones lead to oedema in the mucosa and ulceration leading to fibropurulent exudate into the gallbladder
Pain, SIRS, Pyrexia, Sepsis
What are the possible complications of cholelithiasis?
Impaction of stone without infection but with mucus secretion leading to gallbladder distention
As in mucocele but with infection
Purulent exudate into gallbladder
Fistula forms between gallbladder and ileum, large stones can obstruct ileum
What are the functions of the pancreas?
Insulin, glucagon, somatosatin secretion
Enzymes (proteolytic, amylase, lipolytic)
What is pancreatitis?
What are the acute and chronic effects?
Inflammatory process caused by the effects of enzymes released from pancreatic acini
What are the causes of acute pancreatitis?
Describe the pathogenesis of acute pancreatitis
Juice and bile reflex into pancreas
From reflux or drugs
Blood vessel destruction
What are the biochemical markers of pancreatitis?
What are the symptoms of acute pancreatitis?
How is pancreatitis treated?
Supportive treatments only
Describe chronic pancreatitis
Include causes and symptoms
Parenchymal destruction, fibrosis, loss of acini, duct stenosis
Malabsorption (Steatorrhoea, weight loss)
What is the most common form of pancreatic cancer and what are the risk factors?
90% ductal carcinoma
What are the clinical features of pancreatic carcinoma?
Carcinomatosis (dissemination/spread of cancer
Describe the prognosis for pancreatic cancer
5th cause of cancer death in UK
Best treatment, but only 5-15% suitable
5 yr survival is 15-35%
1 yr survival is 12%