Week 3 Flashcards
Outline the regional variations in water and electrolyte uptake in the large intestine.
The anatomy behind this?
Structural difference:
– Tight junctional resistance increases towards the colon
– Tight junctions in the small intestine are ‘leaky’
(permeable via the paracellular route)
– Tight junctions in the colon are ‘tight’ (impermeable via the paracellular route
Regional variations in uptake mechanisms:
- H2O (majority in the small intestine 6.5 litres)
- Na+ in the jejunum, ileum and colon
Electrolyte uptake: Na+, Cl-, HCO3- and K+ are absorbed isosmotically with water by the villi (as in the renal proximal tubule)
Describe the mechanism of intestinal secretion from the crypts of Lieberkuhn
Zone of cell proliferation in the base of the crypts replaces the villous cells every 48 – 96 hours
Mechanism:
– Cl- enters the cell via the Na++K++2Cl- basal transporter
– Cl- diffuses across the apical membrane through apical Cl- channels (regulated by secretagogues)
– Na+ follows Cl- secretion passively via the paracellular pathway
– H2O follows NaCl secretion
e) List common secretagogues and briefly explain their mode of action
2 groups:
- Hormones/NTs: VIP, ACh, Bradykinin. Lead to release of second messenger e.g. cAMP, Ca2+
- Bacterial enterotoxins: Cholera, E coli leads to release of second messengers e.g. cAMP, Ca2+
Second messages increase anion secretion and inhibit NaCl absorption.
I.e. Secretagogues –> Bowel movement
Digestion and absorption of lipids
- Dietary lipids are hydrophobic (insoluble in water)
- They must be solubilised before digestion and absorption can occur
- Digestion begins the stomach with the action of lingual and gastric lipases
- Digestion is completed in the small intestine with the action of the pancreatic enzymes
Describe the digestion of lipids in the stomach
Stomach churns and mixes lipids to initiate enzymatic digestion
Lingual and gastric lipases hydrolyse 10% of ingested triglycerides to glycerol and free fatty acids
Key role of gastric lipase in lipid digestion in the stomach?
Slows the rate of gastric emptying so that pancreatic enzymes are able to digest lipid
What is secreted in the duodenal and jejunal mucosa in response to the presence of monoglycerides and fatty acids and small peptides and amino acids?
Cholecystokinin secreted from the I cells of the duodenal and jejunal mucosa
How are lipids digested in the SI?
- Bile salts, lysolecithin and products of lipid digestion emulsify dietary lipids.
- Emulsification produces small droplets of lipids dispersed in an aqueous solution creating a large surface area for pancreatic enzyme digestion
- Pancreatic enzymes (pancreatic lipase, cholesterol ester hydrolase and phospholipase A2) and the protein, colipase are secreted to complete digestion
Stages of digestion and absorption of lipids
- Bile salts from liver coat fat droplets
- Pancreatic lipase and colipase break down fats into monoglycerides and fatty acids stored in micelles
- Monoglycerides and fatty acids move out of micelles and enter cells via diffusion
- Cholesterol is transported into cells by a membrane transporter
- Absorbed fats combine with cholesterol and proteins in the intestinal cells to form chylomicrons
- Chylomicrons are released into the lymphatic system
Chylomicrons:
Structure?
Location?
Transport?
Structure: Chylomicrons (100 nm diameter) have a core of triglycerides and cholesterol ester - phospholipids and apoproteins on the outside (80%/20%)
Location: Chylomicrons are packaged into secretory vesicles on the Golgi membrane and are exocytosed across the basolateral membrane
Transport: The lymphatic circulation carries the chylomicrons to the thoracic duct which empties into the blood stream
What structures in the Si and LI are responsible for absorption and secretion?
Small intestine:
Villi – absorption
Crypts of Lieberkuhn – secretion
Large intestine:
Surface epithelial cells - absorption
Colonic glands – secretion
Effect of cholera toxin on intestinal secretion
Activates GCP in epithelial cells of the crypts. Leads to Cl- released into the lumen –> Diarrhoea
In the clinical examination of abdomen/ GU:
What is looked at during close inspection of the hands/arms?
Finger clubbing: Due to Malabsorption, Inflammatory Bowen disease,lymphoma, cirrhosis Asterixis (coarse flapping tremor): Due to hepatic encaphalopathy Leuconychia: White deposits on nails Koilongchia: Spoon shaped nails Palmar erythema Dupuytrens contracture Spinal naevus Purpura
GU/abdomen examination
Intro General inspection Close inspection of the hands Radial pulse BP/temp (on charts)
Chest/axillae/ abdomen: Close inspection of face Close inspection chest/axillae Palpation of chest/axillae Palpate bladder Palpate of kidneys Feel abdominal aorta Percussion liver, spleen and bladder Percussion for ascites Auscultation of the diaphragm
Back:
Inspect
Palpate for renal tenderness and cervical lymph nodes
Other areas:
• Offers to examine groin
• Offers to examine genitalia
• Requests to do digital rectal examination (DRE)
Conditions to look for during close inspection of the face in GU/abdomen of the face
Jaundice Mouth: - Glossitis - Oral candidiasis - Angular stomatisis - Peutz-jegers syndrome - Telangiectasia
How to examine chest/ axillae during GU/abdomen exam?
Inspect chest for spider naevi, gynaecomastia in men, and both axillae for loss of axillary body hair.
Movement, distension, scars, hernia, masses etx.
Palpation: -Superficial to deep - Ask patient to point to painful area -Palpate all 9 regions - Watch patients face Liver: -Begin in right iliac fossa -Ask patients to breath in and o§ut deeply -Palpate upwards to right costal margin - Feel for liver edge descending on inspiration. Shouldn't feel anything
What is Murphy’s Sign?
• Feel for gall bladder tenderness (e.g. acute cholecystitis)
• Patient breathes in whilst you gently palpate RUQ in mid-
clavicular line
• On liver descent contact with inflamed gallbladder causestenderness and sudden arrest of inspiration
What is Courvoisier’s Sign?
- Painless jaundice and a palpable gallbladder
* Likely due to extrahepatic obstructionmE.g. Pancreatic cancer, UNLIKELY to be gallstones
What is the process to check for splenomegaly?
- Ask the patient to breathe in and out deeply
- Palpate upwards to left hypochondrium
- Feel for edge of an
enlarged spleen as it descends on inspiration
Characteristic notch may be palpable
Move hand between each breath
Percussion of liver, spleen and bladder method
Percuss up to right costal margin for lower border of liver
Percuss downwards from just above right nipple for upper border of liver
Percuss towards left hypochondrium for lower border of spleen
Percuss from umbilicus down in midline for bladder
What is ascites?
Causes?
Method?
Abnormal collection of fluid in peritoneal cavity
Causes: – Hepatic cirrhosis – Intra-abdominal malignancy – Nephrotic syndrome – Cardiac failure – Pancreatitis – Constrictive pericarditis etc.
Method:
Start in mid-line
Percuss towards flanks
Shifting dullness and Fluid thrill
How is the diaphragm auscultated?
Listen for normal bowel sounds (up to 2 min)
Auscultate for abdominal aortic bruits
Auscultate renal arteries
Why are the cervical lymph nodes examined?
May indicate local disease
May indicate more distant disease:
– Tumours of the upper gastrointestinal tract may metastasise to the lower part of the left posterior cervical triangle
– Virchow’s node / Troisier’s sign
Rectal examination:
Indications?
Key points?
Indications: – Rectal bleeding – Prostatic symptoms – Change in bowel habit – Possible spinal cord injury
Key points:
- Explain procedure
- Gain informed consent
- Offer a chaperone
How is the female reproductive system examined?
Indications?
Pathology?
Pelvic examination
– Bi-manual = one hand palpates per vagina and other per abdomen
Indications: pelvic pain abnormal vaginal bleeding abnormal vaginal discharge if considering vaginal or uterine prolapse
Female pelvic pathology:
- Ovarian pathology E.g. Ovarian cyst, malignancy
- Uterine pathology E.g. Uterine prolapse, fibroids, cervical carcinoma,
carcinoma of body of uterus
- Vaginal pathology E.g. vaginitis , prolapse
- Pelvic infection (Pelvic inflammatory disease)
- Ectopic pregnancy - do a pregnancy test
- Always consider a pelvic ultrasound scan
How is the male reproductive system examined?
Pathology?
Testicular exam Pathology: – Infection (epididymitis, orchitis, epididmyo- orchitis) – Testicular torsion – Epididymal cysts – Testicular tumours – Indirect inguinal hernia
Inflammatory disorders of the oesophagus?
Acute: Infection in immunocompromised patients. E.g. • Herpes simplex viruses • Candida • Cytomegalovirus(CMV) – Corrosives
Chronic: Specific. E.g. • Tuberculosis • Bullous pemphigoid and Epidermolysis bullosa • Crohn’sdisease Non-specific E.g. • Reflux oesophagitis
What is GORD?
Gastro-oesophageal reflux disease
Causes for reflux oesophagitis (6)
Consequence? Leading to 3 pathologies?
• Regurgitation of gastric contents – Gastro-oesophageal reflux disease (GORD) – ‘Incompetent’ GO junction • Alcohol and tobacco • Obesity • Drugs e.g. caffeine! • Hiatus hernia • Motility disorders
Squamous epithelium damaged –>
– Eosinophils epithelial infiltration
– Basal cell hyperplasia
– Chronic inflammation
Consequences of reflux oesophagitis
Severe reflux leads to ulceration. Leading to fibrosis = stricture + obstruction.
Oesophagus narrower and more rigid
What is Barrett’s oesophagus?
Risk?
Diagnosis?
Longstanding reflex
Aged 40-60
Lower oesophagus becomes lined by columnar epithelium due to intestinal metaplasia
Risk? 100 times more likely to get adenocarcinoma of distal oesophagus
Diagnosis: Gastroscopy reveals red appearance of oesophagus
Two classifications of gastric inflammation?
Acute gastritis:
- Usually due to chemical injury (e.g. drugs / alcohol)
- H pylori- associated
Chronic gastritis:
- Active chronic (H pylori associated)
- Auto immume
- Chemical (reflux)
H pylori-associate gastritis:
- Bacteria shape?
- Transmission?
- Occupies?
- Condition associated with?
- Treatment?
- Two distribution patterns?
- Detections?
Bacteria shape?
-Gram negative spiral-shaped or curved bacilli
Transmission;
-Oral-oral, faecal-oral, environmental spread.
Occupies?
- Occupies protected niche beneath mucus where pH approx 7
- Does not colonise intestinal type eptithelium
Condition associated with?
-90% active chronic gastritis
Treatment?
-Resolves with therapy (double antibiotics + proton pump inhibitors)
Two distribution patterns:
1. Diffuse involvement of antrum and body
• Atrophy, fibrosis, intestinal metaplasia
• Associated with gastric ulcer and gastric cancer
2. Antral but not body involvement • Gastric acid secretion increased
• Associated with duodenal ulcer
Detection:
-Faecal bacterial, urea breath test, gastric biopsy rapid urease test
Chemical (reflux) gastritis:
Caused by?
Results in…
Associated with?
Caused by: Regurgitation of bile and alkaline duodenal secretion
Results in loss of epithelial cells with compensatory hyperplasia of gastric foveae
Associated with:
- Defective pylorus
- Motility disorders
Autoimmune chronic gastritis:
What is it? What happens?
Association?
Risk?
What is it? What happens?
Autoimmune reaction to gastric parietal cells. Serum antibodies to gastric patietal cells and intrinsic factor.
Loss of acid secretion (hypochlorhydria/achlorhydria)
Loss of intrinsic factor
–> Vit B12 deficiency
–>Macrocytic anaemia (pernicious anaemia)
Association?
With gastric atrophy and intestinal metaplasia
Risk?
Gastric cancer
What are the 3 causes for chronic gastritis?
- Autoimmune
- Bacterial infection (H pylori)
- Chemical injury
Peptic ulceration:
What is it? Caused by?
Major sites of ulceration?
What is it? Caused by?
Breach in mucosal lining of alimentary tract as a result of acid and pepsin attack
Major sites: – First part of duodenum – Junction of antral and body mucosa in stomach – Distal oesophagus – Gastro-enterostomy stoma
Causes for peptic ulcers?
– Hyperacidity – H pylori gastritis – Duodenal reflux – NSAIDs – Smoking – Genetic factors – Zollinger-Ellison syndrome
Complications of peptic ulceration?
– Haemorrhage – Penetration of adjacent organs e.g. pancreas – Perforation – Anaemia – Obstruction – Malignancy
Causes for acute peptic ulcers
Acute gastritis
Stress response
Extremem hyperacidity
Where to chronic peptic ulcers tend to occur?
At mucosal junctions e.g. Antrum- body
CHARACTERIC FEAUTRES OF ALL PEPTIC ULCERS
- Necrotic debris
- Nonspecific acute inflammation
- Granulation tissue
- Fibrosis
Causes of chronic duodenal ulcers?
- Increased acid production (can be induced by H pylori)
- Reduced mucosal resistance.
- Gastric metaplasia occur in response to hyperacidity
- Then colonised by H pylori
Risk of malignancy in ulcers?
Gastric: Rare
Duodenal: “Never”
Patholoigy of chronic duodenal ulcer
• Usually small (<20 mm)
• Sharply ‘Punched out’ with defined edges
• Defined structure:
-Granulation tissue at base
-Underlying inflammation and fibrosis
-Loss of muscular propria
-Complication such as “Bleed, burst or block”, Penetration of adjacent orange, malignancy
Patholoigy of chronic duodenal ulcer
• Usually small (<20 mm)
• Sharply ‘Punched out’ with defined edges
• Defined structure:
-Granulation tissue at base
-Underlying inflammation and fibrosis
-Loss of muscular propria
-Complication such as “Bleed, burst or block”, Penetration of adjacent orange, malignancy
What is intrinsic factor?
Intrinsic factor (IF), also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 (cobalamin) later on in the small intestine.
For chronic gastric caused by autoimmune, what is the mechanism + histology + clinical?
Mechanism:
Anti-parietal cell and intrinsic factor antibodies
Histology:
- Glandular atrophy in gastric body
- Intestinal metaplasia
Clinical:
Pernicious anaemia
For chronic gastric caused by bacterial infection of H pylori, what is the mechanism + histology + clinical?
Mechanism:
Anti-parietal cell and intrinsic factor antibodies
Histology:
- Active chronic inflammation
- Atrophy
- Intestinal metaplasia
Clinical:
- Peptic ulceration
- ?Gastric cancer
For chronic gastric caused by chemical injury, what is the mechanism + histology + clinical?
Mechanism:
- Direct injury
- Disruption of mucus layer
Histology:
- Foveolar hyperplasia
- Few inflammatory cells
Clinical:
- Gastric erosions
- Gastric ulcer
What damage can be caused by GI pathogens?
Local inflammation
Ulceration / perforation of mucosal epithelium
Disruption of normal microbiota
Pharmacological action of bacterial toxins
Invasion to blood or lymphatics
Why is the lining of the epithelium perforated?
Due to untreated ulcers
Name 6 bacterial diarrhoea pathogens
Gram neg: • Vibrio cholerae • Escherichia coli • Campylobacter jejuni • Salmonella spp. • Shigella spp.
Gram pos:
• Listeria monocytogenes
V. cholerae: Structure? Characteristics? Serotypes based on? Vaccines?
Structure:
• Gram negative
• Comma-shaped rod
• Flagellated
Characteristics:
• Characterised by epidemics and pandemics
• Human-only pathogen
• Flourishes in communities with no clean drinking water / sewage disposal
Serotypes:
-Based on O antigens
Vaccines:
- Parenteral vaccine: low protective efficiency
- Oral vaccine: Effective and suitable for travellers
Pathogenesis of V. cholerae: Dosage? Main barrier`? Colonisation in SI requires? Produces? Results in?
- Only infective in large doses
- Many organisms killed in stomach
- Colonisation of small intestine involving flagellar motion, mucinase, attachment to specific receptors
- Production of multicomponent toxin
- Loss of fluid and electrolytes without damage to enterocytes
What is the structure of the cholera toxin (CTx)?
What does it cause?
Structure of cholera toxin:
Oligomeric complex and 6 protein subunits.
- 1 x copy of A subunit (enzymatic)
- 5 x copies of B subunit (receptor binding)
Release of cAMP –> Lost of fluid and electrolytes.
Responsible for the characteristic, watery cholera diarrhoea. Acts as secretogogue.
5 potential consequences of cholera infection?
- Fluid loss of up to 1 litre/hour
- Electrolyte imbalance leading to dehydration, metabolic acidosis and hypokalemia
- Hypovolaemic shock
- 40-60% mortality
- <1% mortality if given fluid/electrolytes (ORT)
Structure of E.coli?
Gram neg
Bacillus
Normal GI microbiota, however, strains with virulence factors (e.g. toxins) enabling them to cause disease
Mode of action of E. coli enterotoxins
Enterotoxins secreted into the gut. E. coli has two of them, LT and STa
LT leads of cAMP ==> fluid loss
STa= leads to production of GMP
C. jejuni:
Structure?
Consequences?
Transmission?
Structure:
- Gram neg
- Helical bacillus
Consequences:
- Food associated diarrhoea
- Mucosal inflammation nd luid secretion
Transmission: Consumption of raw/undercooked meat, contaminated milk
Histological appearance of c. jejuni infection?
- Inflammation involves entire mucosa
- Villous atrophy
- Necrotic debris in crypts
- Thickening of basement membrane
Salmonella spp.: Structure? Consequences? Transmission? Key species?
Structure:
- Gram neg
- Bacilli
Consequences: Food associated diarrhoea
Transmission: Consumption of raw / undercooked meat, contaminated eggs and milk
Key species:
- S. typi
- S. paratyphi
What are the stages of a Salmonella infection?
- Ingestion of large numbers of bacteria
- Absorption to epithelial cells in terminal section of small intestine
- Penetration of cells and migration to lamina propria
- Multiplication in lymphoid follicles
- Inflammatory response mediates release of prostaglandins
- Stimulation of cAMP
- Release of fluid and electrolytes causing diarrhoea
S. typhi and S. paratyphi: Cause which enteric fevers?
Role of macrophages?
Cause which enteric fevers? Typhoid and paratyphoid
Macrophages are the site of multiplication and transport around body
What are the two options for typhoid vaccine?
Oral: Live attenuated (booster after 5 years)
Parenteral: Capsular polysaccharide (Booster after 2 years)
Shigella spp.:
Structure?
Results in?
4 species?
Structure: Bacillus Causes shigellosis (bacillary dysentery) 4 species: -S. dysenteriae (most serious) -S. flexneri -S. boydii -S. sonnei
Stages of shigella infection?
- Attaches to mucosal epithelium of distal ileum
and colon - Causes inflammation and ulceration
- Rarely invasive
- Produces Shiga toxin
- Diarrhoea watery initially, later can contain blood and mucus
- Disease usually self-limiting
L. monocytogenes:
- Structure?
- Condition caused?
- Population at risk?
- Presents as?
Structure: Coccobaccilus Condition caused: Listeriosis Population at risk: -Pregnant women] -Immunosuppressed individual -The elderly Presents as: Meningitis
3 viral diarrhoea pathogens?
Rotavirus
Norovirus
Enteric adenovirus
Rotavirus:
Structure?
Common patient?
Transmission?
Structure: Wheel, 11 separate segments of double-stranded RNA
Common: Children <2 years olds
Transmission: Faeco-oral, but may also be faeco-respiratory
Pathogenesis of rotavirus infection?
- Incubation period of 1-2 days
- Replication of virus in small intestinal epithelial cells at tips of villi
- Resultsinvillousatrophy
- Damage caused to infected cells leaving immature cells with reduced absorptive capacity for sugar, water and electrolytes
- Onset of vomiting, diarrhoea lasting 4 –7 days
What is the rotavirus vaccine?
RotaRix, RotaTeq
- Oral administration
- 2-3 doses
- First dose at 6-10 weeks of age
- Live,attenuated virus
Norovirus:
AKA?
Transmission?
Vaccine?
aka winter vomiting disease
Transmission: Faeco-oral, contaminated water / shellfish, fomites
No vaccine
Enteric adenovirus:
Presentation?
Presentation:
- Asymptomatic infections common
- Mild, but prolonged diarrhoea
What is antibiotic associated diarrhoea?
Drugs involved?
Does not involve ingestion of pathogen or toxin
Can arise from disruption of gut microbiota following antibiotic therapy.
Drugs:
• Tetracycline-allows colonisation by Staphylococcus aureus & Candida sp.
• Clindamycin suppresses gut microbiota and allows Clostridium difficile to multiply
• C. difficile infection. is now associated with resistance to vancomycin
Helicobacter pylori.:
- Structure?
- Assoication to disease?
Structure:
- Gram neg
- Spiral
- Flagellated
- Microaerophilic
Disease associations:
- Duodenal ulcers
- Gastric ulcers
- Gastro-oesophageal reflux disease
- Non-ulcer dyspepsia
Key features of H. pylori?
• Acid-inhibiting protein: Survival in
stomach
• Urease – neutralisation of acid pH
• Adhesins – binding to gastric epithelium
• Cytotoxin – damage to gastric epithelium
• Flagellum – movement through gastric mucus layer
Treatment of H. pylori associated Gastritis?
1 week triple therapy
Option 1. Proton pump inhibitor (PPI) + clarithromycin + amoxycillin
OR
Option 2: PPI + clarithromycin + metronidazole
What is food poisoning?
Syndrome is restricted to diseases caused by toxins elaborated by contaminating bacteria in food before it is consumed
4 ingredients in ORS?
- Glucose (anhydrous)
- Sodium chloride
- Potassium chloride
- Trisodium citrate dihydrate
Characteristics of typhoid patients
Blanching rash
Rose spots
In faeces for several weeks after recovery\1-3% become chronic carriers
Public health concern
Bile production vs storage location?
Bile production: Liver
Bile storage and concentration: Gall bladder
What is Glisson’s capsule?
Deep to its peritoneal covering, the liver is completely surrounded by Glisson’s capsule, a thin connective tissue layer that sends extensions into the organ, in between the lobules
Liver arterial supply?
Venous drainage?
The liver is supplied by the (hepatic) portal vein bringing absorbed nutrients from the stomach and intestine; and the hepatic artery which supplies the hepatocytes (liver cells) with oxygen.
Venous drainage is by hepatic veins that enter the inferior vena cava.
Bile drainage from liver to gall bladder?
Bile is drained via canaliculi that lie between the hepatocytes into bile ductules and eventually into bile ducts.
4 liver function?
- Synthesis and secretion of bile.
- Storage of glucose, glycogen, proteins, vitamins and fats.
- Detoxification of metabolic waste.
- Synthesis of blood clotting and anticoagulant factors (fibrinogen and prothrombin).
Constituents of bile
Bile pigments (chiefly bilirubin), cholesterol, phospholipids (lecithin), fatty acids, water and electrolytes.
Where do bile pigments derive from?
What is the role of KUPFFER CELLS?
Bile pigments are derived as the breakdown products of haemoglobin.
Kupffer cells play a role in their formation. Bile salts
are responsible for the detergent and emulsifying effect of bile on fats, they also increase the absorption of fats by the small intestine.
What is the name of the liver functional unit?
Liver lobule
What is the structure of a liver lobule?
Sheets of cells (hepatocytes) radiate outwards from the central vein, which forms the central axis of the lobule.
Sinusoids lie between the sheets and carry blood from the hepatic artery and portal vein (now mixed oxygenated and de-oxygenated blood) to the central vein.
Bile flow is in the opposite direction, in the canaliculi between the hepatocytes.
The bare area of the liver is between which two ligaments?
The coronary and triangular “ligaments” on posterior liver surface
What/where are the 4 lobes of the liver?
Anterior: Left, right (separated by falciform ligament, quadrate
Posterior: Caudate *next to IVC)
What structure make up the portal triad>
Portal vein
Hepatic artery
Hepatic (biliary) ducts
Liver divisions
Anatomically?
Functionally?
Anatomically:
-Right lobe (larger)
(Divided by the falciform ligament and lesser omentum)
-Left lobe
Functionally by vascular distribution:
- Caudate and quadrate lobe are part of left
- Divided by the fossa for the gall bladder and iVC
What are the couinaud segments of the liver related to/
The functions of the liver segments
What are liver ligaments?
Reflections of peritoneum that surround the bare area.
On the left, the coronary ligaments form the left triangular ligament, while on the right, they form the right triangular ligament
Liver lymph drainage?
The lymph vessels leave the liver and enter several lymph nodes in the porta hepatis
The efferent vessels pass to the coeliac nodes
A few vessels pass from the bare area of the liver through the diaphragm to the posterior mediastinal lymph nodes.
How is jaundice cause from lymph drainage of liver
Retrograde tumour spread from the coeliac nodes may involve the hepatic nodes in the porta hepatis and obstruct the bile ducts to cause jaundice
Liver nerve supply?
Sympathetic nerves form the coeliac plexus (foregut, therefore greater splanchnic nerve, T 5 to 9)
The anterior vagal trunk gives rise to a large parasympathetic hepatic branch, which passes directly to the liver
Structure of gall bladder?
Rounded fundus
Body that is its major part Neck that narrows towards the cystic duct
How does bile reach GIT from gall bladder
`the cystic duct combines with the common hepatic duct to form the bile duct and enter the 2nd part of the duodenum with the pancreatic duct at the ampulla of Vater
How is the cystic duct lumen held up?
The mucous membrane of the cystic duct is raised to form a spiral fold that is continuous with a similar fold in the neck of the gallbladder The fold is commonly known as the “spiral valve (of Heister)”, the function of which is to keep the lumen constantly open.
Blood supply of gall bladder?
Arterial: Cystic artery, a branch of the right hepatic artery
Venous: Drains directly into the portal vein
Lymph drainage of gall bladder?
To a cystic lymph node neck GB neck.
- -> Hepatic nodes
- -> Coeliac nodes
Nerve supply of gallbladder?
Sympathetic:
-Foregut (T5-9)
Parasympathetic:
-Vagal fibres from the coeliac plexus.
What is used to surgically locate the cystic artery?
Bounded by?
The Calot's hystohepatic triangle Bounded by: -The edge of the right lobe of the liver -The common hepatic duct -The cystic duct
Referred pain from gall bladder?
Referred pain from the gallbladder is usually to the epigastrium (T7 to 9), but irritation of adjacent peritoneum may involve the phrenic nerve (C3, 4, 5) giving referred pain to the right shoulder tip, via C3, 4 in the supraclavicular nerves
Cause for painless, continues jaundice?
Carcinoma of the head of the pancreas may obstruct the bile duct causing painless, continuous jaundice
Where does common bile duct enter duodenum?
At the major duodenal papilla
What does the ERCP test stand for and identify?
Endoscopic, retrograde, cholangio pancreaticogram (ERCP) with stones in the gall bladder
Where does the transpyloric place lie?
What structures lie on it?
The Transpyloric Plane at L1 is midway between the jugular notch and the pubic symphysis, and through the tips of the 9th costal cartilages
List of structures that lie on it:
- Fundus of gall bladder
- Pylorus
- Neck of pancreas
- Formation of portal vein
- Hilum of kidney (right lower than left)
- Spinal cord ends at L1/2
- Aorta and origin of SMA
- IVC
- 2nd part of duodenum
Functions of the pancreas?
Exocrine and endocrine functions: digestive pro-enzymes secreted via pancreatic duct to 2nd part of duodenum; insulin and glucagon from the islets of Langerhans
Journey of pancreatic duct?
The pancreatic duct begins in the tail of the pancreas and joins the bile duct at the hepatopancreatic ampulla (of Vater), that opens as the major duodenal papilla
What are the 3 sphincters that make up the sphincter of Oddi?
1 around the end of the pancreatic duct (to control flow but prevent bile entering the pancreas)
1 around the end of the bile duct
1 around the combined ducts
Blood supply of the pancreas?
- Coeliac trunk FOREGUT
- Gastroduodenal (direct to pancreas)
- Superior pancreaticoduodenal (to Ant and Post branches)
- Splenic –> Greater and Dorsal Pancreatic branches - Superior mesenteric artery MIDGUT
- Inferior pancreaticoduodenal (to Ant and Post branches)
Mirrored by veins. Draining to portal vein although the portal vein is the mirror of the gasproduodenal artery.
Affect on gallbladder of cholecystokinin?
Contraction which is produced but he mucous membrane of the duodenum on arrival of fatty food from stomach.
Lymph drainage of the pancreas?
Along arteries
Efferent vessels drain into the coeliac and superior mesenteric lymph nodes
Nerve supply of the pancreas?
Comes with arteries and is vagus (PS) + T7-9 and T10-11
What is the method of transmission of intestinal protozoa and helminths?
Faecal-derived materials
Acquired during ingestion of contaminated food or water
Presentation of intestinal protozoa and helminths?
Acute to chronic diarrhoea and inflammation
Name protozoal infection of the GIT, 2 in SI and 1 in colon?
SI: GIardia lambda, crytosporidium parvum
LI: Entamoeba histolytic
Describe the 2 stages of the life cycle of G. lamblia?
- Trophozoite
- Flagellated and bi-nucleated
- Lives in upper part of SI
- Adheres to brush border of epithelial cells - Cyst
- Formed when trophozoite forms resistant wall
- Passes out in stools
- Can survive for several weeks
Pathogenesis of G. lamblia?
Present in duodenum, jejunum and upper ileum
Attaches to the mucosa via ventral sucker
Does not penetrate the surface
Causes damage to the mucosa and villous atrophy
Leads to malabsorption of food, esp. fats and fat soluble vitamins
May swim up bile duct to gall bladder
Clinical presentation of G. lamblia?
Mild infections = asymptomatic
Chronic diarrhoea presents in immunocompromised patients
Stools are characteristically loose, foul-smelling and fatty
C. parvum, transmission and reservoir?
Transmission: Faecally contaminated drinking water
Reservoir: Animals (usually cattle)
Life cycle of C. parvum?
Asexual & sexual development
within host:
• Ingestion of resistant oocysts
• Release of infective sporozoites in small intestine
• Invasion of intestinal epithelium
• Division to form merozoites which re-infect cells
• After sexual phase, oocytes released
Pathogenesis of C. parvum?
- Enters cells of the microvillus border ofsmall intestine
- Remains within vacuole of epithelial cell
- May multiply to give large numbers of progeny, especially in immunocompromised hosts
Presentation of C. parvum?
- Moderate to severe profuse diarrhoea
- Up to 25 litres of watery faeces / day
- Usually self limiting disease
- In HIV positive individuals with CD4+ T-cell counts of <100/mm3, diarrhoea is prolonged and may become irreversible and life- threatening
E. histolytica:
Transmission?
Role of cysts?
Transmission: Ingestion of contaminated food/water, anal sexual activity
Role of cysts:
• Cysts pass through stomach and excyst (break open and release contents) in the small intestine giving rise to progeny
• These adhere to epithelial cells and cause damage mainly through cytolysis
• After mucosal invasion, cysts invade red blood cells giving rise to amoebic colitis
• Trophozoite stages live in large intestine and pass out as resistant, infective cysts
Pathogenesis of E. histolytica?
• Adheres to epithelium and acute
inflammatory cells
• Resists host humoral and cell mediated immune defence mechanisms
• Produces hydrolytic enzymes, proteinases, collagenase, elastase
• Produces protein that lyses neutrophils, the contents of which are toxic to the host
Clinical presentation fo E. histolytica?
- Small localised superficial ulcers leading to mild diarrhoea
- Entire colonic mucosa may become deeply ulcerated leading to severe amoebic dysentery
- Complications include intestinal perforation
- Trophozoites may spread to the liver, and other organs
- Rarely, abscesses spread to overlying skin
Difference between bacillary and amoebic dysentery?
Shigella sp. (bacillary) • Many PMN in stool • Eosinophilsabsent • Many bacilli in stool • Blood/mucus present in stool
Entamoeba (amoebic) • Few PMN in stool • Eosinophils present • Few amoebae in stool • Blood/mucus present in stool
Difference between the treatment of G. lamblia, C.parvum and E.histolytica?
G. lamblia
• Mepacrine hydrochloride
• Metronidazole
• Tinidazole
C.parvum
• Nitazoxanide
• Spiramycin
E.histolytica
• Metronidazole
ORT for all.
Ways to prevent protozoal infections of the GIT?
- Improved hygiene and water supplies
- Eating only freshly prepared food served hot
- Avoiding salads and fruit which cannot be peeled
- Avoiding tap water and ice cubes
What are the 3 categories of helminths?
- Roundworms (nematodes)
- Tapeworms (cestodes)
- Flukes (trematodes)
5 examples of roundworms
1 example of a tapeworm
Roundworm: • Strongyloides stercoralis • Trichuris trichiura • Ascaris lumbricoides • Enterobius vermicularis • Ancylostoma duodenale
Tapeworm:
• Taenia solium
Nematode intestinal infections:
- Transmission?
- Infection by?
- Diagnosis?
Transmission: Through soil Infection by: -Swallowing infective eggs -Active skin penetration by larvae and systemic migration through lung to intestine Diagnosis: Stool microscopy
Have 6 helminth infections of the GIT
- Strongyloides stercoralis
- Trichuris trichiura
- Ascaris lumbricoides
- Enterobius vermicularis
- Ancylostoma duodenale
• Taenia solium
S. stercoralis:
Class of helminth?
Result of infection?
Clinical presentation?
Class: Pinworm
Results in…
- Disruption of SI mucosa
- Villous atrophy
- Marked loss of elasticity of intestinal wall
Clinical presentation:
- Dysentery
- Dehydration
- Malabsorption syndrome
- Anal pruritus
- Associated with appendicitis
T. trichiura:
Class of helminth?
Acquired by?
Class: Whipworm
Acquired by ingesting eggs on veg
A. lumbricoides:
Class of helminth?
Clinical presentation?
Class: Giant roundworm
Clinical presentation: • Allergic reaction in sensitised people • Digestive upsets • Protein/energy malnutrition • Intestinal blockages • Worm may invade mouth nose etc.
E. vermincularis:
Class of helminth?
Presentation?
Class: Threadworm
Presentation:
Intense itching
Secondary bacterial infection = Mild catarrhal inflammation and diarryhoea and slightly eosinophilia
A. duodenale: Class of helminth? Acquired by? Pathogenesis? Presentation?
Class: Hookworm Acquired by walking barefoot in infected areas Pathogenesis: Attaches to small intestine, suck blood and protein, often present in huge numbers Presentation: Hypochromic anaemia
Treatment and prevention of intestinal helminth infections
• Improved hygiene and sanitation are important in prevention of infection
• Specific drugs in lecture on “anti-helminthics”
– Mebendazole
– Praziquantel
4 problems of antiprotozoal and antihelminthic agents
- Large variety of species
- Complexities of their life cycles
- Differences in their metabolic pathways
- Drugs active against protozoa are inactive against helminths
Define the inheritance patterns of:
- Familial Adenomatous Polyposis coli, FAP
2. Hereditary non-polyposis coli, HNPCC (Lynch syndrome)
- FAP = Autosomal dominant
2. HNPCC= Autosomal dominant
2 genetic tests for FAP and HNPCC?
FAP and HNPCC tests:
- Protein truncation
- Direct sequencing tumour support
To describe the molecular mechanisms underlying FAP
In FAP, mutated APC leads to:
- Distorted cytoskeletal network
- Loss of polarity
- Decreased cell-cell adhesion
- Aberrant cell migration
- -> Cancer initiation and progression
To identify additional risk factors for colon cancer
Diet:
- High fibre reduced risk
- High intake of red and processed meats increases risk
- Fish decreases risk
Obesity
Alcohol
How aspirin may protect against colon cancer. Risk?
Aspirin and other NSAIDs inhibit COX-2.
Mechanism of inhibition? COX-2 increased in early stages of colorectal cancer
–> increase prostaglandin synthesis
–> Stimulates proliferation and angiogenesis
–> Inhibits apopotsis
Risk? Less prostaglandins, less bp regulation, increase CV risk
What is beta- catenin?
Catenin beta-1, also known as β-catenin, is a protein that in humans is encoded by the CTNNB1 gene. β-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcription.
In cytoplasm B-catenin + APC –> B-catenin degradation
B-catenin – enter cell nucleus –> B-catenin + TCF –> Transcription and cell division
(TCF= T-cell factor)
Role of b-catenin and APC in wnt signalling and cell proliferation?
WITHOUT Ant SIGNAL 1. Inactive receptor 2. Inactive signalling protein 3. Active APC containing complex 4. Degradation of b-catenin 5. Inactive TCF complex Wnt-responsive genes OFF
With WNT SIGNAL 1. Wnt present and to receptor 2. Active receptor 3. Active signalling protein 4. Inactive APC containing complex 5. Stable b-catenin 6. Active TCF complex Transcription of Wnt- responsive genes leading to proliferation of gut stem cells
Why the colon?
Colon unusual organised means that there is a stem cell population in the centre of the colon, where the wnt pathway is active. Then areas of inactive pathway beyond it.
So areas of varying proliferation
Mutation in APC is also seen in ______ tumours
Mutations of ____ alone is not sufficient to cause cancer
Mutation of APC is also seen in sporadic tumours
Mutation of APC alone is not
sufficient to cause cancer
Which has higher risk of colon tumours, HNPCC or FAP?
Hereditary non-polyposis coli, HNPCC
Repetitive regions of DNA are more susceptible to…
Errors
Difference between FAP and HNPCC in number of polyps, mutation rate, risk of cancer, penetrance
FAP • Large number of Polyps • Low mutation rate • High cancer risk because of high number of polyps • 100% penetrance
HNPCC • Low number of polyps • High mutation rate • High cancer risk despite low number of polyps • 80% penetrance
What is the screening programme in Scotland for colon cancer?
> 50yrs screened every 2 years of occult blood and if positive then colonoscopy
If known FAP/HNPCC: bi annual colonoscopy from 25 years
If at high to moderate risk: Colonoscopy every 5 years from age 50-75
What is classed as “high to moderate risk” of colon cancer?
People with 3+ affected relatives in a first degree kinship with each other
Two affected relatives less than 60 years old in a first degree kinship with each other
What is the progression from polyp to carcinoma in HNPCC?
Intestinal epithelial lining – (APC signal)–> Adenoma (K-RAS –(p53, SMADs) –> Carcinoma
Features of FAP?
Large number of polyps developing in adolescence onwards
90% of patients also have pigmented legions in retina (CHRPE)
Why do defects in APC predispose to cancer?
Tumours suppressor gene. in normal, mutation by chance you are protected. by other working copy of gene. mutation in minority.
In patient who already have mutation, if you get mutation by chance. Patient is no longer protected. More at risk pattients.
Name 4 other tissues affected by FAP
- Gardner Syndrome
- Rare
- Variant of FAP
- Masses of benign tumours
- Jaw cysts
- Sebaceous cysts
- Osteomata
- pigmented lesions of the retina (CHRPE)
Features of HNPCC
- High risk of colon tumours
- Can be underlying cause of other tumour types eg endometrium, ovarian, small intestine, stomach
- Low numbers of polyps
3 gene defect in HNPCC?
MSH2
MLH1 **
MSH6
What is the difference in the chromosomal instability of FAP and HNPCC?
FAP= whole chromosome instabiloty HNPCC= small segments of chromosome instability
Define overweight and obesity in adults and children
Excess adiposity
In children:
Overweight= BMI of +25 at age 18
Obese= BMI 30+ at age 18
Outline the components of energy balance and what factors cause excess weight gain
Energy balance = Energy intake and expenditure equal
Factors which lead to weight gain:
- Lowered physical activity
- Sedentary lifestyle
- Large portion size
- Variety of food options
- Lower income background
Understand the health implications of excess weight gain
CV issues Anxiety Depression Anorexia Arthritis Diabetes Cancer
be able to describe modifiable behaviours in the treatment of childhood obesity
Leptin therapy to those with mutation in leptin gene
What are the two main consequences of childhood obesity?
Endocrine: Insulin resistance/ impaired glucose tolerance: Type 2 diabetes
CVS: Hypertension, dyslipidaemia, fatty streaks, LV hypertrophy
Genetic link to obesity
Evidence: familial, twin, family, functional
Monogenic forms of obesity
- Rare
- Single gene disorders
Polygenic/ common forms of obesity
-Complex interactions between genes and environment
• gene-gene
• gene-environment
[Individual variation in obese phenotype]
Example of environment interaction in the pathogenesis of obesity
Pima in Arizona
• typical American lifestyle
• typical American diet
Pima in Sierra Madre Mountains of Mexico
• traditional methods of farming, cooking, fetching water
• largely unaffected by labour saving devices
Candidate common gene variants predisposing to polygenic obesity
- Peroxisome proliferator-activated receptor ( PPARG) (Pro12ala)
- Uncoupling Proteins (UCPs)
- Beta adrenergic receptors (B3-Trp64Arg)
- FTO
- MC4R…
- NPY2R
- Emerging evidence for gene variants involved in reward behaviour (e.g. DRD2 Taq1A)
- Genes linked to variation in weight through taste (e.g. CD36)
What does GWAS stand for?
Genome-wide association studies
Use of GWAS
Identifies new obesity loci
Whole genome studies:
• systematic analysis of genome
• powered to detect small effects by testing in large populations
Relevance of gene FTO in obesity
• Found on chromosome 16
• Encodes a protein with 2-oxoglutarate-dependent nucleic acid
demethylase activity
• Role in fatty acid metabolism, DNA repair, post-translational changes
• Expressed in brain, pancreatic islet, adipose tissue, adrenal glands
• Polymorphisms on FTO gene robustly linked to BMI & obesity in adults and children
FTO VARIEANTS PREDISPOSE TO OBESITY
- Increases energy intake
- Preference for fat intake
Explain the difference between food allergy and food intolerance
Food allergy: An inappropriate reaction by the body’s immune system to the ingestion of a food that in the majority of individuals causes no adverse effects.
Food intolerance:
General term used to describe a range of adverse responses to food, including allergic reactions, adverse reactions resulting from enzyme deficiencies, pharmacological reactions and other non-defined responses
List some conditions that result from food allergy
Anaphylactic shock
Delayed response
Describe common examples of food intolerance
Peanut allergy Coeliac disease Lactose intolerance Hereditary fructose intolerance Caffeine sensitivity
Incidence definition?
The number of new cases in a population over a fixed period of time
Period prevalence definition?
The total number of existing cases in a population over a fixed period of time
Point prevalence definition?
The total number of existing cases in a population at a specific time
