wk 2 GI and Liver - part 1 Flashcards
liver segments
- 8
- Each has own supply from portal vein and hepatic artery
- Each has branch of bile duct draining it
- Each has segment of hepatic vein draining back into IVC
liver microanatomy
- Hepatic globules each with own supply of hepatic artery, portal vein and bile duct
- Draining into branch of hepatic vein
- Hexagonal shaped segments
- Central vein draining away in the middle
- In between portal triads in Sinusoids are where functions of liver performed
hepatic sinusoid
- Portal triad at one side
- Portal venous blood and oxygenated blood mix and travel along sinusoid towards central vein
- Sinusoid lined by liver sinusoidal endothelial cells
o These maintain blood cells in sinusoid
o Allow passage of metabolites, plasma proteins, lipid proteins, viruses etc into space of Diss
o Hepatocytes then maintain homeostasis, sustaining nutrients, secrete bile and detoxify drugs in space of Disse
o As blood passes along sinusoid metabolic functions of hepatocytes change (in part due to change in oxygenation as you move down this gradient
liver functions
- Nutrient metabolism
- Drug Metabolism
- Protein synthesis
- Secretion
- Storage
- Immunological function
glucose metabolism during fasting
- Dec. insulin and inc. glucagon leading to normoglycaemia
o Glycogen breakdown in periportal hepatocytes
Major glucose store in body
o Gluconeogenesis from
Lactate, pyruvate, amino acids, glycerol
glucose metabolism during feeding
- Inc. insulin and dec. glucagon leading to hepatic glucose uptake
o Glycogen deposition in hepatocytes
lipid metabolism
- Bile digests lipids in the gut -> Chylomicrons -> liver
- Chylomicrons metabolised by lipoprotein lipase -> cholesterol, phospholipids, triglycerides and free fatty
protein metabolism
- Amino acid is absorbed from the small intestine
o Hepatocytes metabolise proteins via the Krebs or citric acid cycle
o -> hormones, neurotransmitters, plasma proteins, nucleotides (purine and pyrimidine)
ammonia
- Absorbed from the gut but also synthesised in the liver
o Detoxified in the liver by conversion to urea by the Krebs cycle
o By product of digestion
albumin
- Albumin
- 10-12g/day and 55% of circulating protein
- Transport proteins
bile
600ml/day made up of
o Bile acids primary (made in liver) and secondary (absorbed)
Allow digestion of dietary fats through emulsification
whats in bile? BILE ACIDS o Phospholipids o Cholesterol o Conjugated drugs o Electrolytes – Na+, Cl-, HCO3- and copper o Bilirubin
bilirubin
- Heme is breakdown product of red blood cells
- In spleen heme broken down to biliverdin -> unconjugated bilirubin
- Transported down by albumin to liver where its conjugated and made soluble
- Then excreted in bile going into deudenum
- Conjugated bilirubin converted to urobilinogen
o Some converted into stercobilin -> gives stools brown colour
o some reabsorbed
o Some absorbed into blood and is excreted in urine
Kidneys convert from urobilinogen to urobilin
And excreted in the urine (giving yellow hue)
- When you get bile duct obstruction you get pale stools this is due to the fact bilirubin is needed to give stools brown colour
vitamin storage
- A,D and B12 are stored in large amounts
- Small amounts of vit K and folate are rapidly depleted with decreased liver function
- Metabolises cholecalciferol vitamin D3 -> activated 25-(OH) vitamin D
mineral storage
- Iron stored in ferritin and haemosiderin
- Copper (can be affected by Wilson’s disease = excess levels of copper)
immune functions of the liver
- ‘firewall” filtering all blood from gut
- Kupffer cells phagocytose pathogens from gut
- Supply of important chemokines
o Interleukins
o Tumour necrosis factor - Priming t cell repsonses
definition of liver cirrhosis
- Development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury
- > portal hypertension and end stage liver disease
- 4000 deaths/ year due to cirrhosis
- > 700 transplants
- Increase in mortality overtime
causes of cirrhosis
- Viral infection o Hep N and C - Alcohol - Non-alcohol steato-hepatitis - Autoimmune disorders o AIH - Cholestatic liver disease o PBC and PSC - Metabolic causes
pathology of cirrhosis
- Chronic injury
- Overtime damage
- Loss of pancrine cells and angiogenesis
- Depends on genetics, alcohol, obesity
- Fibrosis in reversible as you can remove the underlying cause
o However, if underlying cause cont. u get loss of architecture, loss of function, no hepatocyte regeneration -> cirrhosis
o Outcome is liver transplantation
o Once you have cirrhosis once you remove the underlying cause it doesn’t heal
o Once have cirrhosis at risk of hepatocellular carcinoma
hepatocyte injury results in…
- Apoptosis and necrosis of hepatocytes
- Recruitment of macrophages
- Activation of macrophages and hepatic stellate cells
fibrosis
- Inflammatory response leads to secretion of pro-inflammatory and pro-fibrotic mediators
- Trans differentiation of stellate cells into myofibroblasts
- These lead to matrix synthesis with a-SMA and collagen 1 – matrix deposition
- Reduction in matrix degradation
- If remove cause of injury you get dec. prod. Of pro-inflammatory cytokines
o Leads to matrix degradation loss of myofibroblasts too
o Progression of fibrosis
stellate cells
- Important in gen of fibrosis and cirrhosis
- Activation of stellate cell + portal/ perivascular fibroblasts = myofibroblast
- Myofibroblasts lead to inc. collagen synthesis + dec. in matrix metalloproteases
- Collagen accumulation and organ failure
consequence of inc. sinusoidal resistance
-Portal hypertension
o Portosystemic collaterals
Meaning blood can pass from portosystemic to systemic system without going through the liver
• Eg ammonia doesn’t get de-toxified by liver can go to BBB causing cephalopathy
varices
Extra blood vessels around oesophagus and stomach and spleen
Can lead to bleeding
- caused by portal hypertension as blood can’t flow through normal route and so creates an alternative
- bad because blood isn’t filtered by liver
angiogenesis
Inc portosystemic collaterals
Inc. Porto venous blood inflow more hypertension
splanchnic vasodilation
hypotension relative decreased in effective volume vasoconstriction activation. Of reno-angiotensin aldosterone system • surge in water retention • increase fluid vol. • ascites • increased CO • increased venous blood flow – inc. portohypertension
physical signs of chronic liver disease
Liver in cirrhosis can be small or large
- In advanced - small due to high level of scarring
Splenomegaly
- Due to portal hypertension
- Feeds back through splenic vein leading to hypertrophy of spleen
Loss of body hair
- Due to effects on hormones
Spider Naevi
- Due to angiogenic factors released
Neurological effects
- Due to ammonia bypass in liver
Ascites
- Due to portal hypertension
- Fluid retention
how to diagnose fibrosis/ cirrhosis
Liver biopsy
- Gold standard, quantative
- Sampling error (may underscore if chose wrong place), morbidity
Serum markers
- Widely available, non-invasive
- Nonspecific, grey zone for intermediate fibrosis
- Can tell if someone cirrhotic but hard to tell if fibrotic
Elastography
- Non-invasive, fast and user-friendly, validated in chronic hepatitis
- Cost, confounding factors
- Hard to get reading in obese patients
serum markers in liver cirrhosis
ALBUMIN
- Decreases in end-stage liver disease due to decreased synthesis
- T1/2 – 20 days therefore useful in cirrhosis
PROTHROMBIN TIME
- Decreased synthesis of clotting factors (I, II, V, VII, X) -> inc. PT
- In cirrhosis associated with more advanced disease
BILIRUBIN
- Increased in end stage cirrhosis due to decreased clearance
PLATELETS
- Decreased in cirrhosis
- Splenomegaly -> inc. consumption
- Decreased thrombopoietin produced by cirrhotic liver
fibroscans
- Works because liver should be like jelly/elastic
- As more fibrotic liver becomes more solid
- Probe measures the stiffness of liver by sending impulses through liver
- Diff. scores suggest different types of liver cirrhosis and idea of extent of fibrosis
child-pugh score
- Assess risk of mortality after deciding patients cirrhotic
jaundice
- Yellowish pigmentation of the skin, membranes and sclera (conjunctival membrane)
- Jaundice (jaune) = yellow
- Visible at bilirubin level >35umol/L
types of jaundice
- Pre-hepatic (before liver)
- Hepatic (in liver)
- Post hepatic (consequence of something outside the liver)
pre-hepatic jaundice
- Eg Haemolysis
- More bilirubin into system at very beginning
- Too much unconjugated bilirubin for liver to conjugate it all
- As water insoluble, does not enter urine
hepatic jaundice
- Mixed type of jaundice as…
- Liver can’t uptake unconjugated bilirubin and can’t conjugate bilirubin normally
Caused by… Hepatocyte damage due to… - Cirrhosis - Viruses – hepatitis, CMV - Drugs – paracetamol - Alcohol - Sepsis - Right heart failure
post-hepatic jaundice
- Blockage type cause after liver
- Bilirubin still conjugated and so water soluble
- Some water-soluble bilirubin leaks out into blood stream and is excreted by kidney
- Makes urine really dark
- Bilirubin not getting in poo – poo really pale
- ITCHY – due to bile salts not getting through normally and therefore in skin
Caused by… Classifications -> - Within the lumen eg gallstones - Within the wall eg tumours - External compression eg pancreas cancer (squishing bile duct)
obstructive jaundice - malignancy
- hilar cholangiocarcinoma
- hilar lymphadenopathy
- distal cholangiocarcinoma
- ampullary tumours
- pancreatic tumours
whipples
- Operation for obstructive cancers at bottom
- Distal cholangiocarcinoma’s
- Ampullary tumours
- Pancreatic tumours
Take out…
- Gallbladder
- Distal bile duct
- Duodenum
- Stomach
- Pulling up jugular lens and stitching it back together
ERCP - endoscopic retrograde cholangiopancreatography
- A camera you swallow down
- Goes through the stomach into duodenum
- End of it looks straight at ampulla
- Put down wires into bottom of bile duct
- Take samples of cancer for lab
- Put in stents that go through the cancer and give pathway for bile to drain
- This helps with symptoms they get from jaundice
- Can also do this for benign disease
- Eg gallstones
features of obstructive jaundice
PALE STOOLS, DARK URINE, ITCH
obstructive jaundice on examination
- Peripheral stigmata of liver disease…
- Finger clubbing
- palmar erythema (red palms)
- dupuytren’s contracture (palmar thickens, fingers bending over)
- sclera for jaundice
- virchow’s node (lump in neck – sign of cancer)
- spider naevi (capillaries in skin – press them disappear and come back when release)
- gynecomastia
- hepatomegaly
- splenomegaly (portal hypertension)
- ascites
- palpable gall bladder
investigation for obstructive jaundice
haematology
- FBC, if anaemic consider cancer
- Abnormal clotting in liver disease
- LFTs – raised bilirubin
Looking at patterns of liver test (not definitive)
- If ALP> ALT/AST = obstructive picture
- ALT/AST >ALP, liver disease
Liver screening
Ultrasound – gallstone, CBD dilatation, liver/ pancreas mass
- If blockage look for ducts in liver (if they’re blown up its post-hepatic due to high pressure)
CT abdomen with contrast, MRI/BRCP
- Good for showing cancers
- MRI is best test for seeing there’s stones in bile duct itself
Tissue biopsy if above unclear
management of jaundice
Depends on underlying condition
- Treat symptoms
- Analgesia
- IVI
- Antibiotics if septic
- Vit K and chlorphenamine
Treat underlying cause
- Pre-hepatic -> stop haemolytic process
- Hepatic -> anti-virals, prevent deterioration of cirrhosis eg alcohol, drugs
- Obstructive – ERCP/stenting, surgery, palliative care
gall stones basic anatomy
- Gall bladder drains by cystic duct into common bile duct down the way
- Drains upwards after cystic duct joins drains via common hepatic duct
- Divides into left and right branches
- Right into anterior and posterior
- Common hepatic artery comes from the coeliac trunk
- Cystic artery (artery to the gall bladder) comes from right hepatic artery
- Head of pancreas down low at head of pancreas and the ampulla
- Ligament between the liver and the duodenum
- Bile duct
- Hepatic artery
- Portal vein
incidence of gallstones
- 10 to 20% of adults
- 80% asymptomatic
- Females 2:1 ratio to males
- Fair, fat, fertile, forty
types of gallstones
mixed gallstones -> most common
pure cholesterol gall stones
haemolysis/ haemolytic anaemia -> made of unconjugated bilirubin
clinical presentation of gall stones
- Right upper quadrant pain or epigastric pain
- Colicky (get better then worse) or constant
- Dyspepsia, nausea, vomiting
- Can be mistaken for acid reflux
gall stones symptoms
Biliary colic
- Most common
- Pain gets worse then better
- Stones are floating around – sometimes balls get trapped = pain
Acute cholecystitis
- Inflammation and sometimes infection
- Pain starts as colicky but becomes more constant
- Temperature due to inflammation
- Treat with antibiotics
- Sometimes emergency operation
Obstructive jaundice
- If galls tones get out of gall bladder
- Into the bile duct
- Causing jaundice
- ERCP – try to drag stone out into duodenum
Acute pancreatitis
- Gall stone falls out of gall bladder
- Causes pressure change in pancreatic duct as it goes down
- Irritation and inflammation of the pancreas
management of gall stones
- Analgesia
- Antibiotics
- percutaneous drainage
- ERCP
- Surgery
alcohol unit
1 unit = 10ml or 8g of pure alcohol
1 unit processed in one hour
ABV = % alcohol of total liquid volume
Units = ABV% x volume (in litres) (of drink consumed
