GI S7 (Done) Flashcards
List the categories of toxins that may be encoutered in the GI tract
Chemical
Bacteria
Viruses
Protozoa
Nematodes, Cestodes, Trematodes
What methods of defense are used aginst these toxins?
Innate:
Physical
Celullar
Adaptive
What are the innate phyiscal defenses protecting the GI tract?
Sight
Smell
Memory
Saliva
Gastric Acid
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?
Xerostomia:
Lead to microbial overgrowth in the mouth and dental caries
Parotitis:
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
Mycobacterium tuberculosis
Enteroviruses:
Hep A, Polio, Coxsackie
List the protective mechanisms of the small intestine
Bile
Proteolytic enzymes
Lack of nutrients
Anaerobic environment
Shedding of epithelial cells
Rapid transit (Peristalsis)
What is the normal bacterial load in the small intestine?
Normally sterile
What are the main protective mechanisms of the colon
Why are the important?
Mechanism:
Mucus layer covering epithelium
Anaerobic environment
Importance:
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?
Neutrophils
Macrophages
NK cells
Tissue mast cells
Eosinophils
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?
Washerwomans hands:
Severe dehydration
Ricewater stool:
Rapid fluid loss
What is the definition of a ‘portal system’?
Give an example
Definition:
Two capillary systems in series
Example:
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
Viral Hepatitis
Alcohol
Drugs (Paracetamol, halothane)
Industrial solvents
Mushroom poisoning
Describe the effects of liver failure on the GI tract
Infection:
Increased susceptiblity to infection
Toxins, drugs, hormones:
Increased susceptibility
Ammonia:
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
Hepatic fibrosis:
Leads to reductions in liver function (liver failure)
Also portal hypertension (>20mmHg)
Porto-systemic shunting:
Portal hypertension leads to shunting of blood into systemic circulation (therefore toxins are also shunted)
Can cause:
- Oesophageal varices*
- Haemorrhoids*
- Caput medusae*
Describe fully the symptoms of Porto-systemic shunting in liver cirrhosis
Haemorrhoids:
Highly vascular ‘cushions’ in the anal canal become swollen due to increased venous pressure
Oesophageal varices:
Venous dilation in the lower third of the oesophagus due to increased venous pressure
Caput medusae:
Engorged para-umbilical veins visible on the peri- umbilical skin due to increased venous pressure
Ascites:
Portal anstomoses with retroperitoneal veins cused capillary leakage into peritoneum
Splenomegaly:
Congestion due to portal hypertension
Spider naevi:
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?
B lymphocytes:
Production of antibodies (IgE, IgA) for defense against extracellular microbes
T Lymphocytes:
Defense against intracellular organisms
Describe the distribution of lymphatic tissue in the GI tract
GALT:
Gut associated lymphoid tissue is diffusely distributed throughout the gut and surrounding tissues (E.g. Mesentery)
Also nodular in 3 locations:
- Tonsils*
- Peyer’s Patches*
- Appendix*
Describe the drainage of the tonsils and the clincial relevance of this
Drainage:
Drain into cervical lymph nodes in the neck
Clincal:
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?
Peyer’s Patches:
Nodular GALT in the mucosa of the terminal ileum
Clinical:
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?
Obstruction:
Faecoliths
Lymphoid hyperplasia
Lymphoid infection/inflammation
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?
Bile production
Carbohydrate, protein and lipid metabolism
Protein synthesis
Vit D snythesis
Detoxification
Vitamin and mineral storage
Phagocytosis
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 Bilirubin
Serum Alkaline phosphatase
Tests for Synthetic functions:
Serum albumin
Prothrombin time (clotting)
Describe the presentation and classification of jaundice
Yellow pigmentation in eyes and skin
Classified as:
- Prehepatic (Haemolytic)*
- Hepatic (parenchymal)*
- Post-hepatic (Cholestatic)*
What is the cause of prehepatic jaundice?
How is this determined to be occuring clinically?
Cause:
Excessive haemolysis
Liver unable to cope with excess bilirubin
Testing:
Uconjugated hyperbilirubinaemia
Anaemia
What are some of the causes of prehepatic jaundice?
Inherited:
Gilbert’s syndrome
Acquired:
Autoimmune
Acquired membrane defects
Drugs
Burns
What is hepatocellular junadice and how is jaundice determined to be hepatocellular in nature?
Cause:
Deranged hepatocyte function
Element of cholestasis
Testing:
Mixed conjugated and unconjugated hyperbilirubinaemia
Increased liver enzymes
Abnormal clotting (increased prothrombin time)
What are some causes of hepatocellular jaundice?
Congenital:
Gilbert’s syndrome
Inflammation:
Viruses (Hep A, B, C, E + EBV)
Autoimmune hepatitis
Alcohol
Drugs:
E.g. Paracetamol
Cirrhosis:
Alcohol
Chronic hepatitis
Malignancy:
Hepatocellular carcinoma
Metastases
What is post-hepatic jaundice and how might jaundice be determine to be post hepatic in nature?
Causes:
Obstruction of the billary system
Intra/Extrahepatic
Passage of conjugated bilirubin therefore blocked
Tests:
Conjugated hyperbilirubinaemia
Bilirubin in urine
Increased serum liver enzymes
What are the common causes of post-hepatic jaundice?
Intrahepatic:
Heapatitis
Drufs
Cirrhosis
Extrahepatic:
Gallstones
Billary stricture
Carcinoma (E.g. in head of pancreas or Ampulla of vater)
Pancreatitis
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
Explanation:
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?
Acute:
AST/ALT release from hepatocytes
Jaundice
Chronic:
Snythetic failure
Reduced albumin and clotting factors
Increased prothrombin time
List some causes of hepatitis
Viral:
Hep A, B, C
EBV
CMV
Autoiimune
Drugs:
Methyldopa
Isoniazid (TB treatment)
Hereditary:
A1-antitrypsin deficiency
Wilson’s disease
Alcohol
Describe the pathological prgoression in aloholic liver disease
What are some complications?
Progression:
Steatosis (fatty change)
Aloholic hepatitis
Cirrhosis
Complications:
Hepatocaellular carcinoma
Liver failure
Wernicke-Korsakoff syndrome
Encephalopathy
Dementia
Epilepsy
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?
ALCOHOL
Hep B or C
Autoimmune hepatitis
Wilson’s disease
Haemochromotosis
What are the clinical features of cirrhosis?
Liver:
Jaundice
Anaemia
Bruising
Palmar erythrema
Dupuytren’s contracture (fixed flexion deformity of the fingers)
Portal hypertension
Spontaneous bacteria peritonitis
What are the haematological signs of cirrhosis?
Raised ALT/AST
Raised Alkaline phosphatase
Raised bilirubin
Reduced Albumin
Increased prothrombin time
Decreased Na+
What are the management methods for cirrhosis?
Stop drinking
Treatment of complications
Transplantation
Describe the cause, clinical signs and treatment of primary billary cirrhosis
Cause:
Chronic destruction of bile ducts
Clincal signs:
Jaundice
Pruritis
Xanthelasma
Hepatosplenomegaly
Treatment:
Supportive treatment and transplantation
What is hereditary haemochromotosis?
What diseases may occur as a result?
Autosomal dominant disease:
Abnormal iron transport and deposition
Can cause:
Cardiomyopathy
Diabetes
Hypergonadism
Hepatitis/cirrhosis
What is Wilson’s disease?
What can result?
How is it treated?
Autosomal recessive:
Disordered copper transport and deposition
Can cause:
Heaptitis/Cirrhosis
Tremore, dementia
Kidney tubular degneration
Treatment:
Penecillamine (chelation therapy)
What is A1-antitrypsin deficiency?
What can it cause?
How is it treated?
Autosomal recessive:
Deficient A1-antitrypsin
Can cause:
Liver cirrhosis
Emphysema
Treatment:
Transplant
What are the causes of portal hypertension?
Obstruction of portal vein:
Congenital
Thrombosis
Extrinsic compression
Obstruction of flow within the liver:
Cirrhosis
Hepatoportal sclerosis
Schistosomiasis
Where does the hepatic portal system anastomose with the systemic circulation?
Link this to the symptoms of portal hypertension
Oesophageal varices:
Oesophageal branch of left gastric vein (portal) anastomose with the Oesophageal tributaries of azygous system (systemic)
Haemorrhoids:
Superior rectal branch of IMV (portal) anastomoses with the inferior rectal veins (systemic)
Caput medusae:
Portal veins in liver anastomose with ant. abd. wall veins
Ascites:
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
Drugs:
- Paracetamol*
- Isoniazid*
Wilson’s disease
Pregnancy
Alcohol
What are the clinical featuers of fulminant hepatic encephalopathy?
How is it managed?
Symptoms:
Jaundice
Encephalopathy
Loss of consiousness
Hypoglycaemia
Decreased K+/Ca2+
Haemorrhage
Management:
Supportive therapy and transplant
What is hepatic encephalopathy and what might precipitate it?
HE:
Reversible neuropsychiatric deficit
Inability to remove toxins from blood (Ammonia)
Precipitating factors:
Sepsis/Infection
Constipation
Diuretics
GI bleed
Alcohol withdrawal
What are the clinical features of hepatic encephalopathy?
Flapping tremor
Loss of conciousness
Personality changes
Intellectual deterioration (Constructional apraxia, slow, slurred speech)
Give examples of benign and malignant liver tumours
Benign:
Haemangioma
Focal nodular hyperplasia
Liver cysts
Polycystic liver disease
Malignant:
Primary hepatocellular carcinoma
Secondary metastases (20x more common):
- Colorectal (50%)*
- Neuroendocrine*
- Pancreas*
- Lung*
What are the pathological processes which can affect the billary tree?
Obstruction
Infection
Inflammation
Neoplasia
How common are gallstones and what are the risk factors?
10 - 20% of population
Risk factors:
Female
Increasing age
Obesity
Diet
Developed country
Ilial disease/resection
Haemolytic disease
What are the different types of stones that cause cholelithiasis?
Mixed:
80%
Cholesterol with Ca2+ and bile pigment
Pure cholesterol:
10%
Usually solitary
Pigment stones:
10%
Calcium bilirubinate
Multiple small stones
What are the common clincal consequences of gallstone formation?
Biliary colic:
Impaction of stone
Gallbladder contraction (in attempt to clear)
Intermittent pain
Cholecystitis:
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?
Mucocele:
Impaction of stone without infection but with mucus secretion leading to gallbladder distention
Empyema:
As in mucocele but with infection
Purulent exudate into gallbladder
Obstructive jaundice
Acute pancreatitis
Gallbladder perforation
Biliary-enteric fistula:
Fistula forms between gallbladder and ileum, large stones can obstruct ileum
What are the functions of the pancreas?
Endocrine:
Insulin, glucagon, somatosatin secretion
Exocrine:
Fluid (HCO3-)
Enzymes (proteolytic, amylase, lipolytic)
What is pancreatitis?
What are the acute and chronic effects?
Pancreatitis:
Inflammatory process caused by the effects of enzymes released from pancreatic acini
Acute effects:
Oedema
Haemorrhage
Necrosis
Chronic effects:
Fibrosis
Calcification
What are the causes of acute pancreatitis?
GET SMASHED:
Gallstones
Ethanol
Trauma
Steroids
Mumps
Autoimmune
Scorpion bite
Hyperlipidaemia
ERCP/Iatrogenic
Drugs
Describe the pathogenesis of acute pancreatitis
Duct obstruction:
Juice and bile reflex into pancreas
Acinar damage:
From reflux or drugs
Protease:
Tssue destruction
Lipase:
Fat necrosis
Elastase:
Blood vessel destruction
What are the biochemical markers of pancreatitis?
Markers:
Serum amylase
Decreased Ca2+
Hyperglycaemia
Increased ALP/Bilirubin
What are the symptoms of acute pancreatitis?
Severe pain
Vomiting
Dehydration
Shock/SIRS
Ileus (Paralytic)
How is pancreatitis treated?
Supportive treatments only
Describe chronic pancreatitis
Include causes and symptoms
Chronic inflammation
Parenchymal destruction, fibrosis, loss of acini, duct stenosis
Causes:
Chronic alcoholism
Cystic fibrosis
Biliary disease
Symptoms:
Pain
Malabsorption (Steatorrhoea, weight loss)
Diabetes mellitus
Jaundice
What is the most common form of pancreatic cancer and what are the risk factors?
90% ductal carcinoma
Risk factors:
Smoking
Familial pancreatitis
Benzidine
Beta napthylamine
What are the clinical features of pancreatic carcinoma?
Initially symptomless
Obstructive jundice
Pain
Vomiting
Carcinomatosis (dissemination/spread of cancer
Malabsorption
Diabetes
Describe the prognosis for pancreatic cancer
5th cause of cancer death in UK
Resective surgery:
Best treatment, but only 5-15% suitable
5 yr survival is 15-35%
Overall:
1 yr survival is 12%
