Liver Flashcards
Biliary anatomy; Liver anatomy; Liver function; Liver and metabolism; Bile; Liver failure; Bilirubin
Where is the liver located?
Right upper quadrant of the abdomen
What are the liver’s 4 main functions?
Control of synthesis and metabolism of proteins
Maintenance of blood sugar
Lipid metabolism
Metabolism and excretion of bilirubin and bile acids
What are the key functions of bile?
Emulsification and absorption of fat to increase sfa for lipase activity
Cholesterol homeostasis - excreting excess as needed
Toxin secretion - endogenous e.g bilirubin and exogenous e.g drugs
What separates the right and left lobes of the liver?
Falciform ligament
What are the main perfusing vessels of the liver?
Hepatic portal vein and hepatic artery
How are the discrete segments of each lobe separated?
Anatomical borders
Each segment has independent blood supply and bile drainage
Drains into its own vein, which drains into left middle and right hepatic veins then joins the vena cava
How many discrete segments of the liver are there?
8 although IV usually split into upper and lower
What is a hepatic lobule and what does it consist of?
Structural unit of liver tissue
Hexagonal shape
Consists of portal triad that links with adjacent lobules
Rows of hepatocytes (each hepatocyte has sinusoid facing and canaliculi facing sides)
What does the portal triad consist of?
Hepatic portal vein branch
Hepatic artery branch
Bile duct
What is the purpose of the branch of the hepatic artery in the hepatic lobule?
Brings oxygen rich blood into liver tissue to help support the hepatocytes high energy demands
What direction do blood and bile flow in the hepatic lobule?
Blood flows towards centre of lobule
Bile drains to canaliculi which coalesce into bile ducts located around lobule perimeter ∴ bile flows towards perimeter
How do the lobules fit together within liver tissue?
Each portal triad sits at the junction of 3 lobules
Fits together like honeycomb shape
What is the hepatic acinus?
Functional unit of liver tissue
Two adjacent 1/6 lobules
Share two portal triads
Extend as far into lobule as the central veins
What is the three zone model of the hepatic acinus?
Hepatocytes towards outside of lobule receive early exposure to blood contents
Zone 1 - high O2, High toxin risk
Zone 2 - medium O2, Medium toxin risk
Zone 3 - Low O2, Low toxin risk
What are the 5 main cell types of the liver?
Endothelial cells Kuppfer cells Hepatic stellate cells Hepatocytes Cholangiocytes
What are the main features of hepatic endothelial cells?
No basement membrane
Many fenestrations - discontinous endothelium ∴ very leaky
What are the main features and purposes of kuppfer cells?
Macrophage cells, v many in liver
stellate shaped
adhere to internal wall of sinusoid
Release cytokines to activate stellate cells
Eliminate and detoxify substances arriving into liver from portal circulation
What is a hepatic sinusoid?
specialised fenestrated capillary containing kuppfer cells
What are the main features and purposes of hepatic stellate cells?
Located in the space of Disse
quiescent state - Store vitamin A in cytosolic droplets
can become active in response to liver damage or kuppfer cells - fibrogenesis and proliferation leads to collagen deposition in ECM, cauess fibrosis and cirrhosis in liver reducing no of and function of hepatocytes
(when activated referred to as fibroblasts)
What is the space of Disse?
Perisinusoidal space located between sinusoid and hepatocytes
Contains blood plasma and hepatic stellate cells
What are the main purposes of hepatocytes?
Synthesise: -Albumin -Clotting factors -Bile salts Metabolise drugs Process nutrients, detoxify blood and excrete waste substances from the blood in the hepatic portal vein Produce bile
How do the features of hepatocytes relate to its role?
Glycogen to store glucose
Lysosomes to process nutrients
Many Golgi apparatus to package molecules for exocytosis
Abundant RER for protein synthesis (Non essential amino acids, clotting factors, albumin)
Sometimes more than 1 nucleus
Abundant mitochondria because lots of energy dependent processes
Smooth ER for carbohydrate and phospholipid synthesis
Cytoplasmic enzymes to support deamination, glycogenolysis, gluconeogenesis
Peroxizomes for detoxification, waste management, cholesterol and bile synthesis
What is the main purpose of cholangiocytes?
Secrete bicarbonate and water to form bile
Describe the pathway that bile produced in hepatocytes follows
Bile canaliculi→small ductules→small bile ducts→larger bile ducts for each segment→right and left hepatic ducts→common hepatic duct→common bile duct (after common hepatic connects to the cystic duct from gall bladder)→ampulla of Vater (after joining pancreatic duct) enters duodenum at duodenal papilla
Why is bile yellow/green?
Pigments like bilirubin and biliverdin
How much bile is produced?
500mL per day
Where is bile produced?
Hepatocytes secrete 60% total bile: -1° secretion reflective of contents of the hepatic sinusoids Cholangiocytes secrete 40% total bile: -2°modification -Alter pH -Addition of water -Reabsorption of sugar and acids -secretion of HCO3- and Cl- -IgA exocytosed
What are bile acids and bile salts?
bile acids = bile salts 2 1° acids synthesised in liver: -cholic acid =Chenodeoxycholic acid 2 2° acids produced from 1° acids by gut bacteria: -deoxycholic acid -lithocholic acid
What is the purpose of bile salts?
Reduce surface tension in micelles to allow them to form smaller shapes with a larger sfa
What happens to bile salts in bile after it is secreted?
95% reabsorbed in terminal ileum
rest excreted in faeces
What is in bile?
Cholesterol
Bile salts
Bilirubin and drug metabolites
Water and other solutes
What does bile do?
Reduce surface tension of fats
Helps formation of micelles
When is bile produced & released?
Bile constantly being synthesised but stored in gall bladder up the cystic duct due to sphincter of Oddi being closed
Released when sphincter of Oddi relaxed OR when CCK stimulates gall bladder contraction for a ‘big dose’
What does the gall bladder do?
store bile
acidify bile
concentrates bile
How may the enterohepatic circulation increase the half life of drugs?
Liver can process drugs by excreting them via bile, but some may be reabsorbed in the small intestine and re-enter the portal circulation
What is bilirubin derived from?
Haemoglobin breakdown in the spleen
How is bilirubin carried in the blood?
Bound to albumin
How and why is bilirubin conjugated?
Conjugated by glucuronyl transferase to bilirubin glucuronide
Conjugation makes bilirubin water soluble
What happens to bilirubin after it is excreted into the duodenum?
Degraded by bacteria into urobilinogen or stercobilinogen
Some urobilinogen is reabsorbed and excreted by the kidneys in urine
Some urobilinogen converted to stercobilinogen by gut bacteria
Most stercobilinogen oxidised to stercobilin then excreted in faeces (responsible for brown colour)
10% stercobiliogen reabsorbed and returned to liver via enterohepatic circulation
What are some important proteins synthesised/metabolised in the liver?
All circulating proteins except gamma globulins are synthesised in the liver
Albumin - maintains intravascular oncotic pressure and transports water soluble substances and some drugs in the plasma
Transport and carrier proteins e.g. transferrin
All factors involved in coagulation and components of the complement system
Liver degrades amino acids to eliminate nitrogenous waste as urea
How does the liver maintain blood sugar?
Releases glucose into the blood stream in the fasted state by breakdown of stored glycogen (glycogenolysis) or by synthesising glucose from amino acids (muscle) or glycerol (adipose) (gluconeogenesis)
How is the liver responsible for lipid metabolism?
Manufactures most of the body’s cholesterol
Cholesterol used to make bile salts and also needed for hormone synthesis
Liver also synthesises lipoproteins and triglycerides
Why is metabolism and excretion of bile acids in the liver important?
Bile acids are formed from cholesterol and excreted into bile, pass into duodenum where they solubilize lipids for digestion and absorption
What are the most common causes of liver disease in the developed world?
Alcohol liver disease
non alcoholic fatty liver disease
What are the most common causes of liver disease in the developing world?
Chronic viral hep B or C
How does alcohol excess result in liver disease?
Results in fatty change, alcoholic hepatitis, alcoholic cirrhosis
What are early stage symptoms of liver disease?
May be asymptomatic Lethargy Anorexia Malaise Pruritus - itchy skin Right upper quadrant pain
What are symptoms expected as liver disease progresses?
Peripheral swelling Abdominal bloating Bruising Vomiting blood Confusion Somnolence (sleepyness)
What are signs of liver disease and their causes?
Jaundice due to raised bilirubin levels
Reduced capacity to metabolise oestrogens :
-spider naevi - telangiectases
-loss of body hair
-gynaecomastia
-testicular atrophy
-palmar erythema (reddening at thenar and hypothenar eminences)
What are some signs of chronic liver dysfunction?
Xanthelasma - yellow deposit of cholesterol under skin on/around eyelids
Finger clubbing
Pruritus - itchy skin causes scratch marks
Dupuytren’s contracture
Ascites and dilated veins of abdomen
Hepatomegaly - enlarged liver
Hepatosplenomegaly - enlarged liver and spleen
Caput medusa - distended and engorged paraumbilical veins
Oedema
Weight loss and loss of musculature
Hepatic encephalopathy
Fetor hepaticus - musty sweet breath
Hepatic flap - coarse hand tremor
What is liver cirrhosis?
Final common pathway for liver disease
Necrosis of liver cells
Progressive fibrosis and nodule formation → impairment of liver cell function and distortion of liver architecture→portal hypertension and deterioration of liver function
When does cirrhosis develop?
In response to chronic liver injury from any cause
How is the severity and type of liver disease confirmed?
Liver biopsy
What are the 3 histological types of liver cirrhosis?
Micronodular - uniform small nodules
Macronodular - variable sized nodules
Mixed - both small and large nodules
What often causes micronodular liver cirrhosis?
Ongoing alcohool damage
biliary tract disease
What often causes macronodular liver cirrhosis?
Chronic viral hepatitis
What is acute liver failure?
Severe hepatic dysfunction occuring within 6 months of the onset of symptoms of liver disease with clinical manifestation of hepatic encephalopathy or coagulopathy
Massive loss of hepatocytes
How is acute liver failure classified?
Hyperacute - encephalopathy occurs within 7 days of jaundice onset
Acute - encephalopathy after 8-28 days of jaundice
Subacute - encaphalopathy 5-12 weeks after onset of jaundice
What are the general clinical features of acute liver failure?
Jaundice CNS complications Coagulopathy Renal failure Sepsis Cardiovascular complications Metabolic complications
How does sepsis present in acute liver failure?
Bacterial infection in liver failure 90% of cases
Most commonly presents withih 3 days of hospital admission
Fever and leucocytosis absent
What is a common cardiovascular complication associated with acute liver failure?
reduction in peripheral resistance with requires a flex increase in cardiac output to maintain BP
If pre-existing heart disease, cardiac failure and hypotension may result
What are the metabolic complications associated with acute liver failure?
hypoglycaemia
Hypoxia
What are the CNS complications associated with acute liver failure?
Hepatic encaphalopathy
Accumulation of toxins→cerebral oedema→changes in level of consciousness→coma
What are the renal complications associated with acute liver failure?
Hepatorenal syndrome - unexplained renal failure in patients with liver disease
Thought to be due to reduced renal flow in the cortex due to cortical vasoconstriction
Irreversible and rapidly fatal
How does acute liver failure cause coagulopathy?
Liver synthesises coagulation factors and anti-coagulant proteins
Liver also clears activated coagulation factors
Impairment of any of these mechanisms predisposes to bleeding
What features suggest coagulation defects?
Bleeding at any sites
Oozing at venepuncture sites from excessive fibrinolysis
Bruising
What causes chronic hepatic failure?
deterioration in liver function superimposed on chronic liver disease
May progress rapidly
Also called decompensation
What may cause the deterioration in liver function associated with chronic hepatic failure?
may be based on a number of pathological processes, including the underlying disease process itself or different process that undermines the functional reserve of the liver
e.g. infection, haemorrhage, electrolyte imbalance
What is the embryological origin of the biliary system?
Develops from the foregut endoderm around day 29-34
Liver bud breaches into connective tissue mesoderm
Connective tissue and hepatoblasts start to develop
Day 40-55 liver begins to take shape and the gall bladder and biliary ducts are distinguishable
