Gastro - week 1 Flashcards
describe the liver
- Large lobulated exocrine and blood processing gland, with vessels and ducts entering and leaving at the porta
- Enclosed by a thin layer of collagen tissue capsule, mostly covered by mesothelium
- Collagen tissue of the branching vascular system provides gross support
- Parenchymal cells are supported by fine reticular fibres
describe the vessels of the liver
• Portal vein
o Brings food rich blood from the gut
o 75% of blood supply
• Hepatic artery
o Bringing arterial blood
o 25% of blood supply
• Hepatic veins
o Bringing away processed blood into the vena
cava
• Lymphatics
• Hepatic ducts
o Bringing away bile to the gallbladder and gut
There is a nerve supply – parasympathetic and sympathetic supply of perivascular structures but this has very little to do with control of sinusoids
describe the cell structure in the liver
Cells are arranged in perforated plates, one cell wide.
Between the plates are sinusoidal blood channels 9-12um wide, lined by endothelial cells
Scattered in the glandular mass are blood vessels, alone or accompanied by other vessels
These mark out the classic hepatic lobules
describe the liver blood vessels
• Central vein/ terminal hepatic venule
o Very thin wall
o Lies in the centre of lobule
o Sinusoids converge and open into it
• Sublobular/intercalated vein
o Thicker wall
o Lies alone at the periphery of the lobule
• Branch of portal vein
o Again at periphery
o Accompanied by one or more hepatic arteries
and one or more bile ducts
o These three together make the portal triad
o A portal triad lies in a portal area
how does blood flow through the sinusoids
Mixed blood (oxygenated from hepatic artery and not from portal vein) starts from the portal triad and moves along toward the central vein. Flow is very slow and exchange takes place with the cells lining the sinusoids
describe rappaports liver acinus
functional unit comprising of three or so lobules to try and describe the differences in exposure to the blood supply along the various parts of the lobules.
Such differences are reflected in the varied functional activities and susceptibility to toxic agents.
The portal triads are places into the middle instead of peripheral.
There are three zones, each getting closer to the central vein
• Periportal (zone 1) – deals with sampling of components of blood - can detect low blood sugar and send signals to cells downstream (closer to the central vein) to break down glycogen to glucose to enrich the blood. The opposite can be true
• Intermediate (zone 2)
• Perivenous (zone 3)
what can you see in the periportal area in evidence of liver damage?
undifferentiated cells
describe sinusoids
• Lined by fenestrated endothelial cells
o These are loosely attached and rest on microvilli without a basal lamina intervening
o Plasma can therefore pass through the sieve plate, formed by the lining cells, out into the perisinusoidal space of Disse to interact with the hepatocytes
o Disse’s space contains ECM but not a visible basal lamina
• Hold phagocytic Kupffer cells (larger, stellate with a pale oval nucleus)
• Scarce, fat-storing, Stellate cells lie outside of the endothelial cells
o Store vitamin A
o Respond to a variety of insults by making collagen and causing cirrhosis (fibrosis)
describe the sinusoidal wall
• Cleanses the blood (of gut bacterial toxics etc)
• Haemopoiesis in the embryo
• Bringing plasma into intimate contact with the hepatic cell for its many metabolic functions of
o Storage
o Transformations
o Syntheses
o Regulation of plasma concentrations
o Detoxification
o Production of bile
o And assisting defence by production of acute
phase proteins
describe hepatocytes
• Main functional cells of the liver
• 80% of the mass of the liver
• Arranged in plates which anastomose with each other
• The cells are in a polygonal shape and their sides are in contact with sinusoids (sinusoidal face) or another cell (lateral face)
• A portion of lateral faces are modified to form bile canaliculi
• Microvilli are present abundantly on sinusoidal faces and project sparsely into bile canaliculi
• Hepatocyte nuclei are distinctly round with one or two distinct nucleoli
o Most have one nucleus but binucleate cells are common
• Functions o Extensive granular ER Protein synthesis o Smooth ER Steroid hormone and cholesterol metabolism Lipid processing o Very rich in mitochondria o Actin and other microfilaments o Golgi bodies (bile production) o Lysosomes (bile production) o Peroxisomes o Glycogen granules o Fat droplets (appear after meals) o Lipofuscin – pigment from aging
what happens in liver fibrosis
- Fenestrations close up
- This leads to increase in sinusoidal pressure – portal hypertension
- As this gets worse, hepatocytes die and others are surrounded by fibrous tissue
describe bile ducts
- Bile flows in opposite direction – TOWARDS PORTAL TRIAD
- Bile duct formed by many bile canaliculi
- These flow to the canals of herring which have hepatocytes, bile ducts and stem cells
- Common bile duct drains to the ampulla at the sphincter of Oddi and finally to the duodenal outlet
describe lymphatics
- Lymph formed by filtration of plasma into the spaces of Disse as blood flows through sinusoids
- Then lymph percolates between the space of Disse and portal tracts then lymphatics are formed and run along portal vessels and biliary ducts
- The exact correlation between lymphatics and the rest of liver microanatomy is not clear
how many bacteria per gram of colon contents in health
10^12
what factors in the GI tract prevent infection
• pH
o high in stomach which kills
• flow rate
o high at mouth and lower in gut
• mucus
o between gut cells and contents
• competition between bacteria: colonization resistance
• presence of bile and digestive enzymes
• redox potential/oxygen tension
o top of gut is aerobic and bottom tends to be
anaerobicwhat are some pathogenic mechanisms of pathogens
• adherence mechanisms
o stick to gut wall
• toxin production
o often enzymes which cause harm
• motility
o burrow through mucous layer
- site of pathogenicity
- resistance to bile and digestive enzymes
• avoidance of immune mechanisms
o secretory antibody (IgA)
o capsules and lipopolysaccharides
• immunopathological mechanisms
o often what cause the most damage
describe H. pylori
- curved/spiral
- gram-negative
- microaerophiles
- highly motile
- causes gastritis
- gastric and duodenal ulcers – gastric carcinoma
- produces urease (urea ammonia – high pH)
- very common well adapted pathogen
- present in up to 50% in western adults and 100% in developing world
- several putative virulence factors but with no simple correlations with pathogenicity
- developing antibiotic resistance
describe vibrio cholerae
• gram-negative
• comma shaped
• motile with polar flagellum
• water borne pathogen
• causes cholera
• cholera toxin (CT) and toxin co-regulated pilus – both produced by same trigger
• encoded by CT-bacteriophage
• watery diarrhoea – rice water stools
• severe dehydration
• Cholera toxin
o Bipartite toxin
o ADP ribosylating
o 5 B subunits – B BINDS to GM1 ganglioside
on enterocytes
o 1 A subunit – A is ACTIVE part
Cholera toxin sits on the surface of the cell and codes for a product which affects adenyl cyclase – products of adenyl cyclase is cAMP. This builds up in the cell and reverses sodium pump – water tends to go out of the cell
In villus cells – net reduction of absorption of Na and Cl ions and hence water moves out
In crypt cells – increase in secretion of water and Cl
Rehydration therapy – oral/IV
describe shigella sp.
Shigella sp. • Four species o S. dysenteriae (most dangerous) o S. boydii o S. flexneri o S. sonnei (least dangerous) • Members of Enterobacteriaceae • Lactose negative • Non-motile • Cause of dysentery
describe dysentery
- Invades mucosa and damages cells causing blood in diarrhoea
- S. dysenteriae only one to produce shiga toxin
Get into the mucosal cells via M-cells
Then ingested by macrophages which are killed by apoptosis which releases cytokines causing inflammation and tissue destruction
describe C. diff
• Most common cause of nosocomial (healthcare acquired) diarrhoea
• Ranges from asymptomatic carriage to life threatening pseudomembranous colitis
• Highly motile – many flagelli
• Gram positive
• Anaerobic
• Spore former
• Increasingly resistant to antibiotic
• Combination of direct cellular damage and immunopathology
• Necessary stages in pathogenesis
o Colonization resistance compromised by antibiotics
o Gut becomes susceptible to colonization
o Evades immune response
o Produces toxins A and B – causes collapse of cytoskeleton
o Neutrophils and fibrin on the surface of cells cause pseudomembranes – pseudomembranous colitis
o UK type O27s
Have the same tcdC gene deletion
Hyper-toxin producers – produce more than other strains
Resistant to quinolone antibiotics
what are some treatments for C. diff
• Antibiotics
o Metronidazole or vancomycin - anti-anaerobe
o Fidaxomicin – new frontline treatment – very little collateral damage
describe microbial food poisoning
acute gastroenteritis due to eating (or drinking) food containing microorganisms or their toxic products – viable organisms or pre-formed toxins
how do you diagnose microbial food poisoning
• Type of food implicated • Time to develop symptoms (incubation period) • Symptoms (all or some) o Vomiting o diarrhoea (watery, scant, perhaps blood) o Fever o Stomach cramps • How long the symptoms last
