Liver and Friends Flashcards
what are the functions of the liver
- carb metabolism
- fat metabolism
- protein metabolism
- hormone metabolism
- toxin/drug metabolism and excretion
- storsage
- bilirubin metabolism and excretion
where is iron used in the body?
in myoglobin in muscles (300mg)
in haemoglobin in erythrocytes (1,800mg)
where in the body is iron stored?
- 1,000 mg stored in the liver parenchyma
- 600mg stored in reticuloendothelial macrophages
what is ferritin?
- cytosolic protein that stores iron
- small amounts are secreted into the plasma where it acts as an iron carrier
- it acts as a buffer against iron deficiency and iron overload
- plasma ferritin can be used as a marker of overall iron levels stored in the body
problems that can cause ferritin excess
- excess iron storage disorders
- haemolytic anaemia
- hereditary haemochromatosis
- iron replacement therapy
- non iron overload:
- liver disease
- malignancies
ferritin deficiency
iron deficiency is the only known cause of low ferritin
this can result in anaemia
if ferritin is < 20 µg/L this indicates depletion
if ferritin is less than 12 µg/L then this suggests a complete absense of stored iron
difference between RDA and AI
- recommended daily allowance
- AI is adequate intake which is for when there is no RDA
retinal sources
- humans need to make retinal from vitamin A
- vit a includes retinal and carotines
- they can either absorb it directly from meat or produce
- or they can synthesise it form carotines (found in carrots)
functions of vitamin A
- vision
- reproduction
- growth
- stabilising cellular membranes
vit a deficiency
- blindness
- night blindness
- xeropthalmia
- rare in developed countries as the liver stores vitamin A well
- it could be as a consequence of fat malabsorbtion
vitamin A excess
- acute
- abdo pain
- headaches, dizziness, sluggishness and irritability
- desquamation of the skin
- chronic
- joint and bone pain
- hair loss, dryness of the lips
- anorexia
- weight loss and hepatomegaly
- carotenemia
- reversible yellowing of the skin
- does not cause toxicity
vitamin D
- increases intestinal absorbtion of Ca2+
- promotes resorption and formation of the bone
- deficiency
- demineralisation of the bone
- causes rickets in children
- causes osteomalicia (soft bones) in adults
- parathyroid gland secretes PTH
- sun acts on a cholesterol derivative in the skin to form vitamin D3
- both D2 and D3 can be from dietary intake
- inthe liver and kidneys these are processed into 1,25 dihydroxyvitamin D which does the job of maintaining calcium uptake
Vitamin E
- stored in non-adipose cells such as liver and plasma
- there’s also a fixed pool in the adipose cells
- it’s an important antioxidant
- requirements in men
- 4mg/day
- requirements in women
- 3mg/day
- deficiency caused by
- fat malabsorbtion (e.g. CF)
- prem infants
- deficiency causes
- haemolytic anaemia
- myopathy
- retinopathy
- neuropathy
Vitamin K
- rapidly taken up by the liver
- then transferred into very low density lipoproteins and low density lipoproteins which carry it into the plasma
- sources:
- vitamin K1
- present in leafy GREEEEEEEEENS
- vitamin K2
- synthesised by intestinal bacteria
- K3 and K4 are synthetic versions
- vitamin K1
- Necessary for activation of clotting factors 10, 7, 9 and 2
- deficiency
- haemorrhagic disease of the newborn
- rare in adults unless they are on warfarin
- excess?
- k1 relatively safe
- synthetic versions are more dangerous
- could cause oxidative damage, red cell fragility
water soluble vitamins
- move more quickly through the body and therefore require more regular intake than fat soluble
- they include
- C
- B12
- folate (one of the B vitamins)
Vitamin C
- found in citrus fruits
- adults need 40mg/day
- functions:
- collagen synthesis
- carnitine sunthesis
- neurotransmitter synthesis
- antioxidant
- iron absorbtion
- deficiency = scurvy within 50-100 days without VC
- teeth and gum disease
- easy bruising
- hair loss
- treatment for scurvy with vitamin C very quickly relieves symptoms
- full recovery within 48 hours
- excess
- some GI side effects
- no evidence that vitamin c reduces the incidence or duration of colds
vitamin B12
- Found in fish eggs meat and milk
- binds to R proteins which protect it from destruction in the stomach
- IF is produced by parietal cells
- IF-B12 complex is absorbed in the terminal ileum
- B12 is then stored in the liver
- deficiency caused by
- pernicious anaemia
- malabsorbtion
- veganism
- symptoms
- macrocytic anaemia
- peripheral neuropathy in prolonged deficiency
folate
- found in many foods
- a type of vitamin B
- higher requirements during pregnancy
- coenzyme for methylation reactions so is needed for DNA synthesis
- deficiency caused by:
- malabsorbtion
- drugs (e.g. methotrexate)
- diseases that increase cell turnover (e.g. leukaemia)
- deficiency symptoms:
- macrocytic anaemia
- foetal development abnormalities - involving neural tube
clotting factors produced in the liver
- I (fibrinogen)
- II (prothrombin)
- IV
- V
- VI
- VII
measuring clotting factor performance
prothrombin time (extrinsic pathway)
international normalised ratio
Activated partial thromboplastin time (intrinsic pathway
an increased PT could mean liver disease but is not specific to liver disease
what are xenobiotics
- foreign substances that are not normally found in the body and which cannot be used for energy
- can be absorbed from the lungs, skin or ingested
- drugs are xenobiotics
xenobiotic metabolism
- the kidney only excretes water soluble material so xenobiotics need to be converted to hydrophillic metabolites for excretion
- most of this metabolism takes place in the liver
- it normally happens in two phases
biotransformation reactions
- some compounds can be excreted after phase I
- some compounds go on to phase II without a phase I
- most biotransformation occurs in the SER
Cytochrome P450 enzymes
- responsible for most phase I reactions
- there are at least 10 main groups of cytochrome-P450 enzymes
- they are encoded by a family of 57 genes
- features they all have in common:
- present in SER
- oxidise substrate and reduce oxygen
- in electron transport chain, cytochromes reduce O2 as the final electron acceptor
- have a reductase unit which utilises NADPH
- generate reactive free radicals
- inducible
- sustained exposure to substances leads to up-regulation
- patients may need increasingly large doses
one cytochrome-P450 isoform to remember
- CYP3A4
- it is involved in the metabolism of about 50% of all clinically prescribed drugs
- statins
- in the above the 3 refers to the subfamily and the A4 refers to the isoenzyme
- Grapefruit juice inhibits CYP3A4 causing increased blood levels of the drug
anti-psychotics and smoking
- clozapine is an anti-psychodit med
- undergoes serious hepatic metabolism by cytochromes
- CYP1A2 is considered to be the main one
- CYP1A2 is induced by smoking
- smoking cessation while on clozapine needs to be accompanied by a dose reduction of 30-50%
- dose should be increased if someone on clozapine takes up smoking
- things that do the same thing as smoking:
- grilled meat
- rifampicin
- Antibiotic ciprofloxacin inhibit CYP1A2 resulting in higher concentration of clozapine
Four outcomes of drug metabolism
- active drug to inactive metabolite
- active drug to active metabolite
- inactive drug to active metabolite
- active drug to reactive intermediate (may be toxic)
inactivation of a xenobiotic example
- Phenolarbitol is a sedative and anti-epileptic
- lipophilic so distributes into fat tissue
- so only a small amount of active drug is dissolved in plasma and can be excreted by kidneys
- elimination requires
- phase I: introduction of a functional group (OH group)
- phase II: conjugation (to either a glucaronic acid or a sulphate)
- products are polar enough to dissolve and be excreted by the kidneys
example of an active drug being converted to an active metabolite
- morphine is a metabolite of codeine
inactive drug to active metabolite example
- nitroglycerin is metabolised by cytochrome p450 enzymes to produce NO as the active principle
active drug to reactive intermediate (toxification of xenobiotics)
- benzo(a)pyrene from cigarette smoke is converted to very reactive carcinogenic metabolites
- paracetamol is another one
- the product is innocuous and easily excreted
- but the intermediate NAPQI is toxic
- if it’s taken at therapeutic doses then not too much damage can be caused before the intermediate is excreted
- if taken in overdose it overwhelms the phase II enzymes and causes cell damage
- hepatocytes worst affected because they have the highest quantity of cytochrome enzymes
- the person may develop fulminant hepatic failure
- has the same cytochrome enzyme as alcohol
- because it’s inducible, more paracetamol is metabolised to NAPQI in people who drink more
Phase I reactions
- oxidation, reduction or hydrolysis reactions to expose functional groups
- this is so that phase II reactions can take place
Phase II reactions
- these are conjugation reactions to make the compound more water-soluble
- glucoronidation is the most common phase II reaction
- transferase enzymes are mainly responsible for phase II reactions
phase II enzymes can be:
- Microsomal
- found in SER
- inducible by drugs and diet
- Non-microsomal
- found in cytoplasm and mitochondria of hepatocytes
- non inducible
pseudocholinesterase
- a non-microsomal enzyme that acts on succinylcholine
- succinylcholine is a muscle relaxant that is used in anaesthesia
- normally 90-95% of succinycholine is inactivated by pseudocholinesterase
- this means only 5-10% of the drug reaches the neuromuscular junction and paralysis onlu lasts about 5-10 minutes
- in pseudocholinesterase deficiency, paralysis could last 8 hours
metabolism of ethanol
- doesn’t fit phase I and phase II because it doesn’t need to be conjugated for excretion
- only 2-10% is urinated out though because it is used in the liver as a dietary fuel
- this is mainly via the enzyme alcohol dehydrogenase
- ADH creates the toxic intermediate acetaldehyde
- theres another route which uses cytochrome P450 enzymes
- normally this only accounts for about 20%
- but chronic alcohol use can INDUCE 5-10 times as much of the cytochrome p450 enzyme
- this also produces toxic acetaldehyde
- it just does it at a very fast rate and overwhelms the enzymes responsible for clearing the acetaldehyde
- this means that it accumulates in the liver and causes damage
main source and loss of nitrogen in the body
source: dietary protein
loss: gut and kidneys (as urea)
metabolic use of amino acids
- body maintains a pool of free amino acids in the blood
- in the fed state the net contributor is the diet
- in the fasting state the main contributor is skeletal muscle
- bodily protein is in constant turn-over
- degradation via lysosomal and ubiquitin pathways
- protein resynthesis
- amino acids can be used to:
- make protein
- make other nitrogenous products
- synthesise glucose by first removing the amino group
- removed nitrogen is excreted in urea
recommended dietary protein
0.75g/kg/day
50-60g in normal adults
what is the nitrogen balance
examples of positive and negative nitrogen balance
where intake and excretion of nitrogen is roughly equal
important derivatives of glycine
- haem
- creatinine
- purine bases
important derivatives of aspartate
- purine bases
- pyrimidine bases
important derivatives of tyrosine
dopamine
catecholamines
thyroid hormones
melanin
How much total body protein is turned over each day?
How much is excreted as nitrogen?
1-2% of total bodily protein
20-30g of bodily protein
Why are blisters firm?
- high amount of protein in the exudate
- this draws water in
- this is why burns are accompanied by sucha acute protein loss
- widespread tissue damage
- lots of protein lost in the exudate
- increased metabolic requirement for protein at the SAME time as increased protein loss
Two different types of protein degradation
Lysosomal and non-lysosomal
- Lysosomal
- takes place in the reticulo endothelial system of the liver
- sinusoidal epithelial cells
- kupffer cells - immune cells of the liver
- pit cells
- Non-lysosomal degradation
- Normally in a proteasome and is ubiquitin dependent
Protein digestion summary and enzymes
why might the body degrade proteins
- faulty/aging/obsolete proteins
- as a part of signal transduction
- as part of a flexible system that needs to meet the energy requirements of its environment
ubiquitin
- tag for degradation by the proteosome
- it’s a small protein
- three enzymes are involved in making the chains
- E1: ubiquitin-activating enzyme
- E2: ubiquitin-conjugating enzyme
- E3: ubiquitin-protein ligase
- the longer the chain the stronger the signal
- especially if it’s >4
Protein half lives
- some are short and some are long and it’s dependent on their N terminal residues
- some amino acids at the N terminus have a stabilising effect
- some amino acids at the N terminus have a destabilising effect
Ubiquitin targets
- PEST sequence
- proline, glutamic acid, serine and threonine all found in a region of 12aas
- these sequences promote ubiquiting chain formation
- they normally only become exposed when catabolism is needed
- Cyclin destruction box
- similar to PEST but found on cyclins
- obviously need to be degraded very rapildy - CDKs and cell cycle
Proteosome
- Central proteosome with two regulatory caps
- one cap at either end
- the caps are what binds the polyubiquitin
- the cap unfolds the protein and feeds it into the central cylinder
- amino acids released by this process are re-cycled into new proteins
- those that aren’t are rapidly degraded by the urea cycle
what happens to excess amino acids
- they are degraded by the urea cycle
- regardless of their source they are not stored
- those which aren’t immediately incorporated into proteins are degraded
what are the names of enymes that attach and remove phosphate
- attach: kinase
- remove: phosphatase
three amino acids in animals that can be phosphorylated
- serine
- threonine
- tyrosine
- ratio of phsophorylation is 1000:100:1 (in the order above)
- even though the level of tyrosine phosphorylation is minor, the effect is huge
- BCR-Abl is a constitutively active tyrosine kinase
Two forms of malnutrition
- merasmus
- severe wasting simply form insufficient calorie intake
- cancer cachexia
- anorexia
- Kwashiokor
- swelling of the abdomen
- caused by hypoalbuminaemic oedema
- caloric intake is adequate but protein is not
- fatty liver
THE FIVE KEY PLAYERS IN AMINO ACID CATABOLISM
Lysosomal degradation: 4 types
- Macroautophagy
- non-selective ER deriveed autophagosomes engulf cytosolic proteins/aggregates/organelles
- fuses with lysosome to initiate degradation
- Microautophagy
- non-selective invaginations of lysosomal membranes engulf proteins/organelles
- Chaperone mediated autophagy
- chaperones take proteins to lysosomes in response to stressors
- Endocytosis/phagocytosis
- degradation of extracellular substances
control of appetite
- Ghrelin increases appetite
- Leptin decreaes appetite
leptin
- in normal weight people it suppresses appetite
- in the obese there are very high leptin levels
- you get leptin resistance
Ghrelin
increases before meals and stimulates the appetite
Glucose alanine cycle - can you draw the diagram and can you describe the function
- alanine is the principle ammonia scavenger
- glutamate collects the ammonia
- ALT shifts the amino group from the glutamate to pyruvate
- this forms an alanine
- alanine travels in the blood to the liver where the reverse happens
- the NH4+ produced is then turned into urea via the urea cycle
- the pyruvate produced is turned into glucose by gluconeogenesis
- solves two problems with one cycle. moves carbon atoms of pyruvate, as well as excess ammonia, from muscle to liver as alanine. in the liver the alanine gives pyruvate (for gluconeogenesis) and releases ammonia for conversion into urea. The energetic burden of gluconeogenesis being imposed on the liver rather than muscle, so that muscle ATP can be devoted to muscle contraction
most important protein produced by the liver
albumin and clotting factors
albumin
- 9-12g produced by the liver each day but can be increased 3x
- leaves the circulation via the interstitium
- returns via the thoracic duct
- it’s an anticoagulant
- it maintains the colloid osmnotic pressure
- it’s important for binding and transport of other particles
effect of hepatic injury on clotting
- reduced production of clotting factors
- reduced synthesis of inhibitors of coagulation (e.g. albumin)
- reduced hepatic clearance of activated clotting factors
- platelet abnormalities
- number and function
what is the blood supply of the liver?
- Afferent:
- 75% from the Portal Vein
- 25% from the Hepatic artery
- Efferent:
- Hepatic Veins directly into IVC
What is the portal triad?
- bile duct
- portal vein
- hepatic artery
In microanatomy 6 portal triads surround one central vein
Saturated and Unsaturated Fats
- Saturated:
- non bent
- so can line up tight
- solid at room temperature
- Unsaturated
- kinked - either cis or trans
- less lightly packed
- either mono or poly (MUFAs or PUFAs)
- oils
how many calories do lipids yield per gram
9
functions of lipids
- energy reserve
- necessary for some cellular functions
- necessary for all cell membranes
- necessary for hormone metabolism
- necessary for ADEK absorbtion
- cholesterol is the backbone of adrenocorticoids and sex hormones
- cholesterol is also the backbone of vitamin D
energy reserves in blood glucose
40 kcal
lasts a few mins
energy reserves of body glycogen
600 kcal
this would last a day
it’s mainly stored in the liver but some in the muscle too
energy reserves of body lipids
100000kcal
this can last us from 30-40 days
in what form are lipids transported?
- predominantly as triglycerides or fatty acids bound to albumin or as other lipoproteins
- remember TGs cannot diffuse across cell membranes so lipases release FAs to facilitate transport into the cell
Fatty acid uptake
- once they’ve been broken down from TG the FAs can diffuse across the membrane
- they can also undergo facilitated transport
- if there is increased FA (supply)
- or if there is increased receptors (demand)
Fatty Acid Transporter systems
Can you draw the diagram?
- FA binding protein
- this can be induced by increased fatty acid uptake by the cell
- FAT - fatty acid translocase
- FATP - fatty acid transport polypeptide
effect of insulin on lipid metabolism
- promotes fat storage in adipodicytes
- stimulates LPL –> breakdown of TG & release of FFA to be transported to adipocytes and stored as TG
- reduces activity of hormone sensitive lipase to reduce FA export from adipocytes
Insulin resistance:
- increased lipolysis in adipocytes leading to increased TG in the circulation
- increased supply of FA to adipocytes which leads to increased uptake
- this is often coupled with high glucose
- this means less demand for lipids from the liver to be used for energy
- this means that a fatty liver will ensue
- more fat to the liver
- less fat from the liver used
insulin resistance and fatty acid uptake (adipocytes and hepatocytes) can you draw the diagram
De novo lipogenesis in the liver
- Dependent on insulin conc and sensitivity
- more insulin = more lipid synthesis &vv
- the liver does this to create lipids for:
- energy source
- as stuctural components for cells
- the liver does this by serially lengthening Acetyl-CoA via:
- decarboxylative condensation reactions
- the rate limiting step is:
- Acetyl-Coa –> Malonyl CoA via Acetyl CoA carboxylase
- Also related to the amount of FAS (fatty acid synthetase)
FAS
- expressed predominantly in the liver
- activated by insulin
- inactivated by glucagon
- negative feedback: increased FAS in hepatocytes decreases FAS synthesis
Cholesterol
- liver is the major organ that produces cholesterol
- 90% of cholesterol is endogenous
- the only export of cholesterol is through bile
Fatty acid export from the liver
- ApoB100 is synthesised in the rER
- Lipid components are synthesised in the sER and added to ApoB
- ApoB complex is transported to the golgi where it’s glycosylated
- glycosylated Apo’s bud off the golgi and migrate to the sinusoidal membrane of the hepatocyte
- vesicles fuse with the membrane and a VLDL is released
What increases FA oxidation
FFA release from adipodicytes
this is increased by glucagon
and decreased by insulin
3 locations of Lipid Oxidation in the liver
- peroxysomal B-oxidation
- mitochondrial B-oxidation
- ER omega oxidation (Cytochrome p450 catalysed)
Mitochondrial B oxidation
- progressive shortening into acetyl-CoA subunits
- these are condensed into ketone bodies
- these enter the TCA cycle
- regulated by:
- carnitine concentration
- certain drugs like alcohol inhibit B oxidation
Peroxisomal B oxidation
- the main role of this is for detoxification of:
- very long chain fatty acids
- C-27 bile acid intermediates
- other toxic lipids
- 4 step process repeatedly shortens chain length
- there’s lots of redundancy (each step can be done by a couple of enzymes to ensure that even if there are problems the system keeps going)
- disruption leads to micro-vesicular steatosis
Microsomal omega oxidation
- normally a minor pathway but increases as the fat load increases
- CYP4A enzymes oxidise saturated and unsaturated fatty acids
- there’s omega hydroxylation in the ER followed by decarboxylation of the omega fatty acid in the cytosol
- they can then enter the B oxidation cycle
What are PPARs
- peroxisome proliferator activated receptor
- there are 4 (alpha, gamma, beta and delta)
- they are involved in lipid homeostasis
- alpha, beta and delta facilitate energy combustion
- gamma facilitates energy storage
- alpha is a lipid sensor and a transcription factor
- if alpha isn’t working it leads to steatosis
what is steatosis?
abnormal retention of lipids within a cell
stages of liver damage
- Normal liver
- this gets fat deposits on it and becomes a Fatty liver which is enlarged
- this becomes inflamed (steato hepatitis) because of the lipid toxicity and scarring forms this is Liver Fibrosis
- This growing of the connective tissue destroys liver cells and this is Cirrhosis
Developing a fatty liver
- excess dietary fat/overall caloric intake leads to increase in plasma TG
- also leads to increased release of FAs from adipodicytes and uptake by hepatocytes
- There’s a decreased demand for fuels leading to increased storage
What is NAFL
- Non-alcoholic fatty liver
- it’s overstorage of unmetabolised energy exceeding the energy combustion capability of oxidation\
- it leads to liver cirrhosis
- Incidence:
50% diabetic patients (including lean diabetics)
75% of obese patients
98% of morbidly obese patients
What is hepatic steatosis
- a type of NAFL
- this is when fat content of the liver exceeds 5-10% the weight of the liver
What is Steatohepatitis
- this is when the fat becomes inflamed
- this is due to the fatty hepatocytes apoptosing and releasing TGs and toxic FAs
- the FAs result in oxidative stress
- this results in proinflammatory cytokines from Kupffer cells
- this is hepatitis
- stellate cells are also activated
- this leads to fibrogenesis
- the high capacity of the liver to repair itself has been overtaken and we got scarring
- at the end there’s relatively less fat but lots of scarring
Alcohol and fatty liver
- associated with fatty liver because it is so calorific and metabolised in the liver
- it also inhibits PPAR alpha leading to decreased fat oxidation
- the very fatty liver leads to cirrhosis
Glucose and the Liver in the fed state: can you draw the diagram?
what energy source fo RBCs use?
- They don’t have mitochondria so can’t make ATP
- they rely on a constant stream of glucose that they convert into pyruvate and lactate
Effects of cortisol on fuel metabolism
Effects of adrenaline on fuel metabolism
How much bile is produced by hepatocytes each day?
- between 200ml and 1000ml
what is the function of bile?
- lipid digestion and reabsorbtion
- cholesterol homeostasis
- excretion of lipid soluble xenobiotics/drug metabolites
Bile acids
- AKA bile salts
- Make up 50% of the dissolved constitiuents of bile
- syntheised from cholesterol in the pericentral hepatocytes
- primary bile acids:
- cholic acid (CA)
- CDCA
- these are both water soluble
- they are conjugated with glycine or taurine to make them more hydrophillic and acidic before secretion into the canaliculus
bile in fasted state
- travel down hepatic duct into the gall bladder where it can increase in concentration by up to 10x
bile in fed state
- CCK secreted by the duodenum
- this contracts the gall bladder
- it relaxes the spincter of oddi
- this resultd in the secretion of a concentrated solution of bile
- the gall bladder remains concentrated so that synthesised BA goes directly to the gut
where does the portal vein collect blood from?
collects blood from the superior mesenteric vein ( venous drainage of the small and large intestines)
Enterohepatic circulation
- 95% of bile acids secreted by a hepatocyte have been previously secreted
- bile acids remain in the lumen
- then in the jejunum and the ilium they are reabsorbed
- this is via teh apical sodium bile acid transporter (ASBT)
- the bile acids re-enter the liver via the portal circulation
- bile acids are taken up by hepatocytes, reconjugated and secreted into biliary canaliculi
- there are usually 2-3 cycles per meal
blood supply of gall bladder
arterial: cystic artery
venous: no discrete venous drainage - blood seems to drain directly into the liver
Hepatic plate can you draw the diagram
Blood supply to the liver
- 80% is from the hepatic portal vein
- 20% is from the hepatic artery
What is Bilirubin
- it is the haem breakdown pigment (dark brown)
- becomes more concentrated during storage in the gall bladder
- gives faeces its colour
what’s in bile
- Bile acids
- Water and electrolytes
- Cholesterol
- Pigments
Exocrine pancreas
- this is 90% of the pancreas
- ducts are lined by simple cuboidal epithelium
- acinar cells
- store zymogens that will be activated later
- Centriolobular cells
- procude HCO3- and Mucin
- Apical cells
- produce pro enzymes
stimulation of exocrine function of the pancreas
- luminal acidity detected in the duodenum
- Enteroendocrine cells secrete CCK
- causes apical cells to secrete pro-enzymes
- also causes gall bladder to contract
- S cells secrete secretin
- causes centrolobular cells to secrete mucin and HCO3-
endocrine pancreas
- islets of langerhans
- Beta cells
- insulin
- Alpha cells
- glucagon
- Delta cells
- somatostatin
- this reduces secretion by parietal cells
- somatostatin
- Beta cells
liver embryology
- endodermal outgrowth of the foregut
- bile produced from 12th week
pancreas embryology
- dorsal and ventral buds
- ventral bud
- uncinate process and inferior portion of head
- dorsal bud
- everything else
- ventral bud
cellular composition of the islets of langerhans
- beta cells: 65-80%
- alpha cells: 15-20%
- delta cells: 3-10%
what nerve is the liver supplied by and what nerve roots is this from
the liver is part of the foregut and therefore supplied by the greater splanchnic nerve (T6-9)
from which layer of the trilaminar disk do hepatocytes develop from
the endoderm
overall describe the embryology of the liver
liver buds develop anteriorly and then swing to the right, fusing with the posterior abdominal wall
what nerve supplies the pancreas?
the pancreas is part of the foregut and therefore supplied by the greater splanchnic nerve (T6-9)
from what layer of the trilaminar disk does the pancreas develop?
endoderm
give a very brief description of the embryology of the pancreas?
- The pancreas develops as dorsal and ventral buds
- They rotate posteriorly and fuse together
- The ventral pancreas becomes the head and uncunate process of the pancreas
- As a result, the superior mesenteric vein and artery get sandwiched
LDL
formed in the plasma
these deliver cholesterol to cells throughout the body
exocrine pancreas
- dark staining acinar cells make up the majority of the pancreas’s bulk
- they release proenzymes in granules to break down carbs, protein and lipids
- the proenzymes are activated by enteropeptidases in the duodenum
- acini also release bicarbonate to neutralise the chyme
HDL
formed in the liver. these remove excess cholesterol from the blood and the tissues
VLDL
these are synthesized in hepatocytes
they carry triglycerides from glucose in the liver into adipodicytes
what process converts alanine to pyruvate?
transamination
why must ammonia be cleared?
it can cross the bb barrier and can be neurotoxic
Affect of CCK on the pancreas?
causes the release of the enzymes from the cells by exocytosis.
lymphatic drainage of the liver
space of disse –> lymphatic channels in portal tract –> lymphatic channels of hepatic hilum –> cisterna chyli –> thoracic duct
thoracic duct drains into the circulation at the confluence of the left internal jugular vein and the left subclavian vein
What is this? talk about it
- these are biliary canaliculi and sinusoids
- sinusoids are fenestrated capillary vessels
- the capillary wall is too collapsed against adjoining cells to be seen
- the vessels sit on a mesh of reticulin (collagen III)
- they are seperated from the hepatocytes by the space of Disse
- endothelial cells discriminated from Ito cells and hepatocytes by their small dense nuclei
what is this? what are the blue things? and what do they do? what dye has been used?
- these are Kupffer cells in the lining of the sinosoids
- they are the resident macrophages of the liver
- they are important for host defence as well as (in part) the production of bilirubin
- their presence has been demonstrated because they phagocytosed india ink
what epithelium lines the billiary tree?
- cuboidal epithelium
- in the smaller vessels it is simple but then towards the distal end it is stratified
what epithelium lines the gallbladder? what is their special adaptation?
simple columnar
they have poorly developed microvilli which are used for the reabsorption of water in order to concentrate the bile
how much of the mass of the gland does the exocrine portion of the pancreas account for?
90%
what is this? what type of epithelium is it?
This is the wall of the gall bladder
- lining is towards the bottom
- this is a simple columnar epithelium
- the holes at the bottom are the poorly developed microvilli where the lining has been thrown into folds to reabsorb water
- you can see the wall above is connective tissue and smooth muscle
- it also contains blood vessels
how are enzymes secreted from the pancreas?
pancreas is a wholly serous gland (watery & enzyme rich)
produces various enzymes which are packaged together in secretion granules at the apex of each cell
when food enters the duodenum they are induced to release their stored enzymes by CCK
these only become activated when they reach the alkaline environment of the duodenum
affect of secretin on the pancreas?
stimulation with secretin causes the pancreas to release an alkaline fluid
this fluid is mainly produced by the centro-acinar cells and small duct cells
what is this? what epithelium lines it? what is either side?
- this is a picture of a large pancreatic duct
- the epithelium of the duct is simple cuboidal
- at a more distal end it may become stratified
- duct cells produce most of the fluid component of the secretion
- The pancreas is a bunch of grapes
- each grape has a narrow stalk duct that connects it to the main duct
- larger ducts join
- eventually one or two main ducts enter with the common bile duct into the second part of the duodenum
what is this and what are the arrows pointing to?
- this is exocrine pancreas
- the acini are the spherical clumps of cells
- the arrows point to centro-acinar cells which can be seen inside several of the acini
