wk 1 GI and LIver Flashcards
structures entering and exiting the liver
(a) Portal vein bringing food-rich blood from the gut.
(b) Hepatic artery bringing arterial blood.
(c) Hepatic veins taking away processed blood into the vena cava.
(d) Lymphatics taking away some lymph.
(e) Hepatic ducts removing bile to the gallbladder and gut
liver blood supply
Hepatic artery – 25%
o Fully oxygenated blood to supply blood to organ
Portal vein – 75%
o Drains directly from the gut
o Any absorbed food that’s broken down goes into this vein to the liver
nerve supply of the liver
sympathetic & parasympathetic supply of perivascular structures, but very little at sinusoidal level
- Nerves have vv little to do with the control of the sinuses
structure of a liver lobule
- cells are arranged in perforated plates (these are one cell wide)
- Between these plates are sinusoidal blood channels
- This is the way the exchange of nutrients takes place between sinusoidal vessel and perforated plates (hepatocytes)
- blood channels 9-l2 µm wide, lined by endothelial cells
- Scattered in the glandular mass are blood vessels, alone and accompanied by other vessels.
- The distribution of these vessels defines or marks out the classic hepatic lobules
3 types of liver vessel
- central / terminal hepatic venule
- sublobular/ intercalated veins
- branch of portal vein
central vein/ terminal hepatic venule
- very thin wall
- lies in the centre of a lobule
- with sinusoids converging towards and opening into it
sublobular/ intercalated veins
- thicker wall
- lies alone at the periphery of the lobule
branch of portal vein
- at the periphery of the lobule
- accompanied by one or more small hepatic artery
- one or more bile ducts lined by cuboidal epithelium and lymphatics
portal triad
- portal vein + artery + bile duct
- the area in which they lie is a portal area
hepatic vein
- all the lobules stuck together forming a big central vein
bile duct
the portal vein and hepatic artery
go from liver to small intestine
moving bile from liver where it helps to digest food
liver acinus
the smallest functional group of the liver
- rappaport’s liver acinus represent’s a functional unit comprising parts of three or so lobules
- tries to explain the diff. in exposures to the blood supply among various parts of lobules
territory of an acinus
one final branch of the portal vein as its axis
subdivided into…
- periportal
- intermediate
- perivenous (close to central vein) zones
liver sinusoids
low pressure vascular channels that receive blood from the portal triad
- lined by fenestrated epithelial cells (loosely attached)
- phagocytic KUPFFER cells (immune cells)
- these phagocytose intruders + signal other cells to come help
space of Disse
between sinusoid and hepatocytes
- contains blood plasma
- allow protein and other blood plasma components to enter hepatocytes form sinusoids
- contain STELLATE CELLS
stellate cells
- sit just outside the endothelial cells
- store vit. A
- when activated they produce collagen
- first pathophysiological event that underlies liver cirrhosis
sinusoidal wall provides…
- blood cleansing
- haemopoeisis in the embryo
- bringing plasma into intimate contact with the hepatic cell for its many metabolic functions
metabolic functions of hepatic cells
storage synthesis, reg. of plasma conc. detox. production of bile assisting defence by producing acute-phase proteins
hepatocytes
- main functional cell of liver
- space hepatocytes arrange that anastomose with one another
- cells are polygonal shape
- sites in contact with sinusoids or neighbouring hepatocytes called the lateral faces
- lateral spaces is where bile is formed
- > called BILE CANALICULI
- microvili on sinusoidal faec (inc. surface area to inc. exchange of nutrients)
- also in bile canaiculi
- hepatocyte nuclei are distinctively round
what happens when liver gets inflamed
- lots of inflammatory cells in sinusoids
- kupffer cells activated
- stellate cells activated and produce collagen
- fenestrations start to close up
- sinusoidal pressure inc.
- first step in cirrhosis and portal hypertension
AS THINGS GET WORSE MANY HEPATOCYTES DIE
areas that die are replaced with fibrous tissue
irregular pattern of liver architecture in liver damage
o the portal triads expand and bridge
o extensive collagen deposition
o nodule formation
o hepatocytes are surrounding by closed gates and collagen
o this stage is called established liver cirrhosis
bile pathway
- blood flows from portal triad to central vein
- bile flows in opp. direction…
o as bile produced in hepatocytes – they communicate and create a bile duct
o therefore, bile duct formed by several bile canaliculi together
o they end up in a bigger bile duct within the portal triad
o bile ducts get bigger and bigger
o -> common hepatic duct -> common bile duct -> ampulla (areas called sphincter of Oddi) -> Duodenal outlet
o Following this route, the bile finds its way from the liver into the gut to facilitate digestion of food
where are liver stem cells
Canal of Hering/ cholangioles
liver lymphatic system
- Drainage system of the liver
- Lymph is formed by filtration of plasma into the spaces of Disse as blood flows through the sinusoids
o What doesn’t come back through sinusoids goes into the lymph - Small lymphatics percolate through space of Disse and portal tracts
- Run along portal vessels and biliary ducts
- Eventually lymph comes out and joins systemic circulation
things that effect gut ecosystem
pH flow rate - high flow at top of gut _ low flow rate at bottom mucus competition with other bacteria presence of bile and digestive enzymes redox potential/ oxygen tenion - top of gut arobic - bottom of gut anaerobic
pathogenic mechanisms of GI pathogens
- adherence
- toxin production
- motility
- site of pathogenicity
- avoidance of immune mechanisms
- immunopathological mechanisms
helicobacterpylori
- First recognised in early 80s
- Curved/spiral, Gram-negative, microaerophile
- Motile
- Causes gastritis, and gastric and duodenal ulcers (occasional gastric carcinoma)
- Produces urease (urea -> ammonia)
o Produces a cloud of ammonia in stomach to neutralise stomach acid - Very common, well adapted pathogen
- Present in 50% of western adults, and 100% in developing world
- Several putative virulence factors but with no simple correlations with pathogenicity
- Is developing antibiotic resistance!
vibrio cholerae
- Gram-negative, comma-shaped bacterium
- Motile with polar flagellum
- Water-borne pathogen
- Causes cholera
- Virulence factors -> cholera toxin & toxin co-regulated pilus
o These are co-regulated
o Pilus means an adherence mechanism - CT – bacteriophage encoded
- If bacteria don’t have the virus it isn’t pathogenic
- Watery diarrhoea – rice-water stools (bits of mucus in a clear diarrhoea)
- Severe dehydration
mechanism = cholera toxin
guts vili
Vili cells work by pumping in chloride and sodium ion
Absorbing water and these ions into cell then into bloodstream
- When chlorae present it sits on this cell and codes for adenyl cyclase
- One product of adenyl cyclase is cyclic AMP
- High levels of AMP reverses sodium pump
o Only get small amount of sodium and chloride and water intake
o Membrane becomes non-absorptive
guts crypts
- produce mucus and fluid etc
- When cholera is there it makes water pour out more
- Produces more chlorine
- Becomes a secretion cell more than it was
shigella SPP
Four species - S. dysenteriae - S. boydii - S. Flexneri - S. sonnei Written above in order of how dangerous they are Members of Enterobacteriaceae Lactose-neg., non-motile They cause bacterial dystery
Bacterial dystentery - Bloody diarrhoea - Invasion of mucosa by shigella - S. dysenteriae causes most severe o Only one of the genus to produce shiga toxin - S. sonnei casues least severe disease
Pathogenesis
- Mainly a disease of the colon, but sometime watery diarrhoea in ileum at the start
- Bacteria enter mucousal cells via M-cells – ingested by macrophages
- Macrophages killed by apoptosis – release of cytokine – inflammation – tissue destruction
clostridium difficile
- Most common cause of nosocomial diarrhoea, with a severity spectrum from asymptomatic to life-threatening pseudomembranous colitis
- Steadily increasing since the 1980s and is now endemic in healthcare institutions and the community
- Found in many children
- Flagella
- Highly motile
- Gram-positive
- Pink bits where spores are forming
- Anaerobic
- Increasingly resistant to antibiotics
The disease (CDI)
- A spectrum
- Diarrhoea/ simple colitis
- Pseudomembranous colitis
- Fulminant colitis (white plagues in colon)
Combination of direct cellular damage and immunopathology
A disease of hospitalised elderly??
treatment of bacterial infection
- kill the bacteria with an antibiotic
- got to be a vv specific antibiotic
- neutralise the toxins
- prevent attachment of the toxin
- modulate the inflammatory response
Antibiotics used… - metronidazole or vancomycin or other
- Fidaxomicin
o Drug of choice in many places
o Highly cloridium specific
o Doesn’t destroy other bacteria in the gut so less recurrence
Prevention and control
Infection control
- Removal of spores of C. Difficile from environment
Antibiotic Stewardship
- Restriction of antibiotics known to precipitate CDI 3rd gen cephalosporins, clindamycin, fluoroquinolones
campylobacter species
-Microaerophilic, gram-negative curved rods, grow well at 42 degrees celsius
-Related to birds
o Found in gut of birds
o In lots of chicken
-Commonest cause of diarrhoea in the developed world
-C. jejuni and C. coli
-Associated with poultry (frozen), wild birds and other animals – milk and water
-Sporadic infections
-Incubation – 24-72 hrs
-Last about a week
-Rare but significant cause of Guillain-Barre Syndrome (peripheral neuropathy)
o Immune response to nerves triggered by campylobacter
o Acute problem – better after few days/ weeks/ months
non-typhi salmonella SPP
- Major cause of foodborne disease world-wide
- Associated with poultry/ eggs
- Sporadic and outbreaks
- Incubation 6-48 hrs
- Duration 1-7 days
- Often serious – fever, diarrhoea, vomiting
