Liver Flashcards
What are the lobes of the liver?
Left
Right
Caudate
Quadrate
On which surface is the bare area of the liver?
Diaphragmatic
Not covered by peritoneum
(right lobe)
What is the caudate lobe in-between?
Groove of IVC & fissure for ligament venosum
What is the quadrate lobe in-between?
Gallbladder & fissure for ligament teres hepatis
What are the 6 main ligaments of the liver?
Falciform ligament Lesser omentum Ligamentum venosum Ligamentum teres hepatis (round ligament of liver) Coronary ligament Triangular ligament
On what surface of the liver is the falciform ligament found?
Anterosuperior
Separates R & L lobes
What does the lesser omentum attach to?
Lesser curvature of stomach & posterior aspect of liver
Attaches along line of fissure for ligament venosum
What is the ligamentum venosum a remnant of?
Ductus venosus in foetal circulation
Shunt to bypass liver
Is ligamentum venosum or ligamentum teres more superior?
Venosum - superior to porta hepatis
Teres - inferior to porta hepatis
Where does the ligamentum teres hepatis run & what is it a remnant of?
Free edge of falciform ligament
Remnant of umbilical vein
What does the coronary ligament do?
Attaches the superior surface of the liver to the inferior surface of the diaphragm
What are the anterior & posterior layers of the coronary ligament continuous with?
Anterior - falciform ligament
Posterior - lesser omentum
What is the right triangular ligament formed by?
Anterior & posterior layers of coronary ligament converging
What is the left triangular ligament formed by?
Falciform ligament & lesser omentum
Is the caudate of quadrate lobe more superior?
Caudate
What is Calot’s triangle?
Space forms by common hepatic duct, cystic duct & inferior border of liver
What is the hepatic portal vein formed from?
Splenic vein & superior mesenteric vein
What is the structure of a liver lobule?
Hexagonal with a portal triad at each corner & a central vein in the middle
What occurs in a liver lobule?
Blood leaves venule & arteriole to travel to central vein through sinusoids (spaces)
Blood mixes
What are the bile canaliculi?
Between hepatocytes
Drain bile secreted by hepatocytes into bile ductile
Flow direction opposite to sinusoids
What are the structures in a portal triad?
Arteriole
Venue
Bile ductile
What is a liver acini?
Two portal triads & 2 central veins in adjacent lobules that are both supplied by the portal triads in question
What are the sections of the pancreas?
Tail Body Neck Head Ucinate process
What passes between the neck & ucinate process of the pancreas?
Superior mesenteric artery (& vein)
What part of the pancreas is not retroperitoneal?
Tail
Where do the exocrine secretions of the pancreas go?
Intercalated ducts join to form interlobular ducts
Drain into main pancreatic duct
What is the arterial supply of the pancreas?
Neck, body, tail - pancreatic branches of splenic artery
Head, ucinate process - superior & inferior pancreaticoduodenal arteries (from gasproduodenal/superior mesenteric arteries respectively)
What are the sections of the gallbladder?
Fundus
Body
Neck
Describe the biliary tree
R & L hepatic ducts join to form common hepatic duct
Common hepatic duct & cystic duct join to form common bile duct
Common bile duct & pancreatic duct join to form ampulla of Vater
Drain into 2nd section of duodenum via major duodenal papilla & sphincter of Oddi
What is a feature of the cystic duct?
Bidirectional
Controlled by spiral vale
What is the arterial supply of the gallbladder?
Cystic artery
What is the innervation of the gallbladder?
Parasympathetic by CNX
Innervation causes contraction & movement of bile into cystic duct
What is the sympathetic & sensory innervation of the gallbladder?
Coeliac plexus - greater & lesser splanchnic nerves
What is the main stimulus for the secretion of bile?
CCK
Hormone secreted by duodenum
What is the role of the spleen?
Acts as blood filter, removing old RBCs
Has role in immune response
What is the arterial supply of the spleen?
Splenic artery?
splits into 5 - highly vascularised
What are the 2 ligaments of the spleen?
Gastrosplenic
Splenorenal
Where are Ito cells found & what do they store?
Perisinusoidial space
Vitamin A
How is vitamin D activated?
D3 synthesised in UV tradition Transported to liver Converted into pro hormone calcidiol Enters circulation to kidney Converted into calcitriol (biologically active form)
Where is vitamin E stored?
Hepatocytes
How is iron taken up by a cell?
Binds to plasma glycoprotein transferrin in bloodstream
When encounters transferrin receptor on cell, taken up by receptor-mediated endocytosis
Vesicle containing transferrin-iron complex has pH reached by pumping of H+ into vesicle
Causes transferrin to release iron
Transferrin continues through endocytotic cycle to be released back into the bloodstream
How is iron stored?
Free iron is toxic to a cell (catalyses formation of free radicals from ROSs)
Stored in protein complex ferritin
Mostly found in liver
What is an xenobiotic?
Chemical substance present in an organism that is not normally present (or in much higher amounts)
What is xenobiotic metabolism?
Process by which xenobiotics are removed - mostly occurs in liver by hepatic enzymes
What are 2 types of enzyme?
Microsomal - SER of cells, primarily liver, drug biotransformation reactions
Non-microsomal - mostly cytoplasm & mitochondria of hepatocytes, non-specific, most conjugation
What is the type of reaction that mainly uses microsomal enzymes?
Phase I
Describe the phase I reaction of xenobiotic metabolism
Activate xenobiotic molecules by adding or exposing functional groups that are reactive
Describe the phase II reaction of xenobiotic metabolism
Mostly conjugation - new compounds synthesised
What are the functions of albumin?
Maintenance of oncotic pressure Binding & transport of large hydrophobic components Antioxidant Anticoagulant Antithrombotic effects
Define oedema
A build up of fluid in the interstitial space
What are complement factors?
Part of innate immune system
Proteins work to enhance the ability of phagocytes & antibodies to clear tissues of pathogens
Circulate in inactive form
Describe the ubiquitin-proteasome pathway of protein degregation
Small peptide ubiquitin attached to intact protein that is being degraded
Ubiquitin then guides protein to larger protein, proteasome, which breaks down the protein
Describe transamination
Used when there is a surplus of essential amino acids so non-essential amino acids can be make
Amino group from amino acid that is to be deaminated transferred to a keto acid, producing a different keto acid & a different amino acid
Done by transamines - group of enzymes that are found in cytosol & mitochondria
R1CHNH2COOH + R2COCOOH > R1COCOOH + R2CHNH2COOH
What is oxidative deamination?
Amino acid group on amino acid removed, along with H on central atom to form ammonia
Replaced by O derived from water, which double bonds to carbon
Forms keto acid to enter Krebs
RCHNH2COOH + H2O + coenzyme > RCOCOOH + NH3 + coenzyme-2H
What are the 3 main sources of amino acids in the body?
Ingested proteins
Synthesis of non-essential amino acids
Breakdown of proteins
What is the purpose of the glucose/alanine cycle?
To transport amino groups & carbons from muscle tissues to the liver
Describe the steps of the glucose/alanine cycle
- Muscle tissues break down amino acids & produce glutarate
- In this, pyruvate from glycolysis is transaminated by alanine transaminase to make α-ketoglutarate & alanine
- Alanine is transported in blood to liver
- Alanine transaminated with α-ketoglutarate to produce pyruvate & glutamate
- Pyruvate enters the gluconeogenesis pathway to produce glucose
- Glucose is transported in the blood to muscle tissue
- Undergoes glycolysis & produces pyruvate (cycle restarts)
Describe the steps of the urea cycle
+Ammonia & CO2 combine with ornithine to make citrulline
+Cirtulline combines with another ammonia on an aspartate molecule to form argininosuccinate
+Argininosuccinate breaks down to give fumarate & arginine
+Arginine is cleaved by enzyme arginase to regenerate the ornithine, also producing a molecule of urea
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What are the causes of ammonia associated neurotoxicity?
Severe liver disease
Blood in liver doesn’t get exposed to enough parenchymal cells of the liver for the ammonia to be removed
Not enough functional hepatocytes
Increased resistance to blood flow
How are micelles prevented from re-aggregating into large fat droplets?
Bile salts on the surface
What is a lipoprotein?
A single layer of protein molecules that form a sphere around triglycerides & other hydrophobic molecules
What is a chylomicron?
A lipoprotein formed in the intestinal epithelium
How do chylomicrons enter body tissues?
Through pores in walls of lacteals (lymphatic system) that drains into circulation
What occurs to the triglycerides in the capillaries?
Lipoprotein lipase acts on chylomicrons & breaks down the triglycerides into monoglycerides & fatty acids when at destination tissue
What are chylomicron remnants?
Chylomicrons that pass through the capillaries with some TGs & cholesterol still inside
Travel to liver
Special receptors on surface of hepatocyte stimulate uptake of chylomicron remnants
How is bile concentrated in the gallbladder?
Active transport of Na+ out of bile, with H2O following by osmosis
What does the liver do with chylomicron remnants?
Liver combines contents of chylomicrons with FAs & package them into very low density lipoprotein
VLDLs circulate in blood
If VLDLs also pass through capillaries with small amounts of TGs still in them, they return to the circulation in the form of intermediate density lipoproteins
IDLs can be converted by liver to LDLs
LDLs carry cholesterol back to tissues & deposit it there
Describe the steps of haemoglobin & bilirubin metabolism
1) Haem in erythrocytes
2) Breakdown in spleen by macrophages
3) Haemoglobin into haem & globin (globin catabolised into component amino acids)
4) Iron group removed, leaving porphyrin ring
5) Ring broken into straight chain molecule, unconjugated bilirubin (toxic)
6) UCB binds to albumin & is transported in the blood to the liver
7) Albumin-UCB complex enters space of Disse where they dissociate (albumin reenters circulation)
8) UCB transported into hepatocytes via a bilirubin transporter
9) UCB acted upon by enzyme UDP glucuronyl transferase, which attaches a glucuronic acid to the UCB to make it bilirubin monoglucuronide
10) ^ acted upon again by UDP glucuronyl transferase to make bilirubin diglucuronide
11) Mono + di make conjugated bilirubin, which is stored in the gallbladder as bile
12) CCK released upon eating & gallbladder contracts
13) CB converted into urobilinogen by action of intestinal microbes in lumen of intestine
14) Most of urobilinogen converted into sterobilinogen then to stercobilin - excreted in faeces
15) Some urobilinogen reabsorbed into blood, then back to liver, then reused
16) Some reabsorbed urobilinogen transported in blood to kidneys, & converted into urobilin - secreted in urine
What is jaundice?
Increased level of bilirubin in the blood & tissues
What are the 3 types of jaundice?
Pre-hepatic
Hepatic/infra
Post-hepatic
What is pre-hepatic jaundice?
Problem before conjugation of UCB to CB
Due to increase in breakdown of hb so liver cannot cope with the extra load & it builds up in the blood
Insoluble so cannot be excreted so builds up in tissues
Toxic & can cross BBB
Sickle cell, anaemia
Raised serum UCB levels, normal CB levels, normal urine & stool colours
What is hepatic jaundice?
Damage to liver/hepatocytes
Liver cannot conjugate UCB so build up of UCB
If problem with transporter protein on bile canniculi side, also build up of CB in blood
Alcoholic liver disease, hepatitis, cirrhosis, Gilbert’s syndrome
CB is water soluble so dark urine
Last of urobilinogen so pale stools
What is post-hepatic jaundice?
Obstruction of biliary tree
Increased CB levels in blood
Gallstones, biliary structure, pancreatitis, pancreatic/biliary carcinoma
Dark urine, pale stool
Pruritus (itching) symptom as bile salts enter circulation
Where is HCO3- secreted from in the exocrine pancreas?
Duct cells
Describe the process of HCO3- secretion
Resting state - CFTR channels aggregated at luminal surface & tubulovesicles containing H pumps scattered in cell
Stimulated - CFTR channels organise on apical membrane & tubulovesicles move to basolateral membrane
H+ pumped out of cell into blood by secondary AT for Na+
In blood H+ + HCO3- > H2O + CO2
CO2 diffuses into duct cell, CO2 + H2O > H2CO3
Catalysed by carbonic anhydrase, H2CO3 > H+ + HCO3-
H+ pumped out again
HCO3- diffuses into duct lumen
What catalyses the conversion of trypsinogen to trypsin (a protease)
Enterokinase
Trypsin (+ feedback loop)
What catalyses the conversion o chymotrypsinogen to chymotrypsin
Trypsin
What are the pancreas innervated by?
CNX parasympathetic (rest & digest) - enhances secretion
What is cholecystokinin secreted by?
Enteric endocrine cells of duodenum
What is secretin produced by?
Endocrinocytes in epithelium of duodenum
What is secretin stimulated by & what are its actions?
Low pH
Stimulates secretion of water & bicarbonate ions
What are the walls of sinusoids made up of?
Endothelial cells with fixed macrophages & ito cells
What are the sinusoids separated from the cords of hepatocytes by?
Space of Disse
What is the biliary tree lined by?
Cuboidal epithelium
What is the gallbladder lined by?
Simple columnar epithelium
What are the ducts in the pancreas lined by?
Simple columnar epithelium that may become stratified at distal end