Gastrointestinal Week 2 Flashcards
1
Q
What is the macroscopic structure of the liver?
A
- weights ~1.5kg
- situated in R hypochondrium and epigastric region under the diaphragm
- covered by the ribs
- ANTERIOR:
- > right and left lobe, divided by falciform ligament, from which ligamentum teres extends which is a remnant of the umbilical vein
- > along the top edge of the liver is the coronary ligament with a R and L triangular ligament at each end
- > the falciform, coronary and L/R triangular ligaments connect the liver to the diaphragm and anterior abdominal wall
- entire liver covered by fibrous layer called Glisson’s capsule
- FROM ABOVE:
- > bare area of liver on top of R lobe that has Glisson’s capsule but is not covered by peritoneal covering, is in direct contact with the diaphragm
- > IVC towards R lobe, caudate lobe towards left lobe
- POSTERIOR:
- > hepatogastric and hepatoduodenal ligaments emerge from falciform ligament
- > caudate lobe (superior) and quadrate lobe (inferior)
- > GB and porta hepatis can also be seen
2
Q
What are hepatic recesses and name some clinically relevant ones?
A
Spaces between liver and surrounding structures where fluid can gather forming an abscess.
1) L/R subphrenic spaces between diaphragm and liver either side of falciform ligament
2) L/R subhepatic spaces between inferior surface of liver and transverse colon
3) Morison’s pouch: the most posterior and superior aspect of the R subhepatic space. It is the deepest part of the peritoneal cavity where fluid is likely to gather in a bed ridden patient. Also known as HEPATORENAL RECESS as it is located between liver and peritoneal surface of right kidney
3
Q
What is the blood supply and pathway to/through the liver?
A
Receives blood from 2 sources:
1 - hepatic artery (20-25% of blood) gives O2 blood from coeliac trunk
2 - portal vein (70-75% blood) gives deO2 blood that is nutrient rich from stomach/spleen/intestines
- blood from 1 and 2 mixes in hepatic sinusoids where vascular exchange occurs with the liver hepatic cells
- after passing through sinusoids, blood collects in hepatic veins -> IV -> enters R atrium of heart
4
Q
How is bilirubin metabolised?
A
- Every 120 days, RBC’s are phagocytosed by macrophages of RES in the spleen and bone barrow
- the Hb gets broken down into: heme (porphyrin ring), iron which is recycled and globin monomers which are recycled
- Haem —(haem oxygenase)—> biliverdin —(biliverdin reductase)—> bilirubin
- at this stage bilirubin is unconjugated (water insoluble) and so cannot be removed from the body
- the UC bilirubin is bound to albumin and carried in the blood to the liver
- albumin has hydrophilic outside and hydrophobic inside and carries bilirubin by interacting with its hydrophobic part and so transports it in a hydrophilic shell
- in the Space of Disse, the albumin and bilirubin dissociate and the albumin is left behind in the SoD while the bilirubin is carried into hepatocyte cells by sinusoidal bilirubin transporter
- the UC bilirubin is then converted by —(UDP glycoronyl transferase)—> into conjugated bilirubin
- there are two forms of conjugated bilirubin (one of two forms: bilirubin monoglucoronide and bilirubin diglucoronide)
- C bilirubin accumulates in the GB with other components to form bile which is secreted into intestines when needed for fat breakdown
- intestinal bacteria HYDROLYSE CB -> urobilinogen
- intestinal bacteria OXIDISE urobilinogen -> stercobilin (gives faecal colour)
- XS urobilinogen is absorbed into blood and travels to kidneys where it is OXIDISED to urobilin (gives urine colour)
5
Q
What is portal hypertension and how is it caused?
A
Increased resistance to blood flow in the portal venous system, due to a sustained increase in portal venous pressure.
- can be caused by various conditions that increase resistance to bloodflow:
- > cirrhosis
- > obstructive thrombosis
- > narrowing of portal vein before it enters iver
- cirrhosis is the main intrahepatic cause, where bands of fibrous tissue and nodules disrupt liver architecture and increase the resistance to blood flow
6
Q
What complications can develop from portal hypertension?
A
Oesophageal varices:
- increased pressure causes dilation of venous channels behind the obstruction and collateral channels open, connecting the portal circulation with the systemic venous circulation
7
Q
Describe briefly what ascites is and how it occurs:
A
- when amount of fluid in peritoneal cavity increases
- portal hypertension increases hydrostatic pressure causing fluid release
- portal hypertension -> systemic vasodilation -> renal vasoconstriction -> activation of RAAS -> more Na retention -> fluid accumulates
8
Q
Describe what splenomegaly is and how it occurs:
A
- spleen progressively enlarges due to shunting of blood into the splenic vein
9
Q
Describe briefly what oesophageal varices are and how they occur:
A
- due to portal hypertension and cirrhosis there is obstruction of venous blood flow, so blood tries to find another way back to the heart
- large collateral channels develop between portal veins and systemic veins
- caput medusa form when veins around the umbilicus dilate and open up (i.e. reopening of the foetal umbilical vein which has not been totally obliterated)
- dilated veins at the bottom of the oesophagus form varices
- if these bleed they are very difficult to stop bleeding and can be life threatening
10
Q
How can you treat bleeding oesophageal varices?
A
- balloon tamponate
- ligation (band around bleeding vessel)
- B-blockers (propanol) used to reduce BP by lowering blood pressure flow, therefore less pressure in the collateral vessels and the oesophageal vessels that are bleeding
11
Q
What is the total iron content of the body and where is the iron distributed?
A
4g
- 3g in bone marrow/RBC’s
- 100mg enzymes
- 200-300mg in myoglobin
- 200-500mg in RES
12
Q
How is iron balance maintained in the body?
A
The amount of dietary iron that is absorbed is regulates as there is no excretory mechanism for XS iron in the body
13
Q
How is iron stored?
A
Mainly as ferritin (soluble, safe storage and readily available).
Can also be stored as haemosiderin (insoluble conglomerates of ferritin) but in this form iron is slowly available.
14
Q
How is iron transported in the blood?
A
Transported in blood by a glycoprotein called transferrin.
- transferrin is synthesised by hepatocytes
- when iron levels are low Tf production increases
- when iron levels are high Tf production decreases
- Tf has two binding sites (Y)
- normal saturation of Tf with Fe is ~30%
- only 4mg iron bound to transferrin at any one time but 50mg of iron are transported by transferrin per day
- the highest concentration of Tf receptors are found on RBC precursors and most iron delivered to erythrocytes is used for haem synthesis by the ALA-S2 protein
15
Q
What two forms does iron exist in and how are these absorbed?
A
Haem: in red meat and easily absorbed in the duodenum by enterocytes.
Non-haem: in white meat, green veg and is more difficult to absorb.
- > must be released from food by acid digestion and proteolytic enzymes
- > must be reduced from ferric to ferrous form by DUODENAL CYTOCHROME B1 (taking vitamin C supplements can aid this process)
16
Q
How is iron absorbed from the blood into enterocytes?
A
- taken into enterocyte by divalent metal transporter 1 (DMT1) which is an electrogenic pump thats expression is up-regulated in iron deficiency
- once in the enterocyte, ferroportin and hepcidin export the Fe into the circulating plasma
- ferroportin is a transmembrane protein essential for iron release
- hepcidin interacts with ferroportin to increase/decrease iron release into the plasma
17
Q
What is the RES and what is its function?
A
- the reticuloendothelial system is part of the immune system with phagocytic cells located in reticular connective tissue
- RES iron is stored as ferritin or haemosiderin
- macrophages store ~500mg iron
- macrophages must obtain their iron by digestion of RBC’s and not through transferrin
18
Q
Describe iron deficiency anaemia (IDA) and some of its causes:
A
- when transferrin saturation is only 15%
- RBC’s are hypochromic (pale) and microsytic (small)
- in young females may be due to blood loss of pregnancy
- in IDA there is malabsorption of iron as villi in the duodenum are destroyed by lymphocytes which infiltrate the lamina propria
- common cause of GI blood loss
19
Q
What is haematinic deficiency?
A
- deficiency of nutrients like iron, vitamin B12 etc. which are needed for the development of blood cells in bone barrow
- can commonly occur in coeliac disease with deficiencies in:
- > folate
- > iron
- > vitamin B12
20
Q
What is hereditary haemochromatosis (HHC) and how can it be caused?
A
- gene mutation (homozygous C282Y mutation of HFE gene)
- autosomal recessive disorder causing iron overload
- HFE (human haemochromatosis protein) is responsible for controlling synthesis of hepcidin
- loss/inappropriate hepcidin expression causes XS GI absorption of iron and increased Tf saturation
- Tf saturation can reach 100% and the danger is that some Fe may be present in the blood that is not bound to Tf = dangerous
Common feature = restrictive cardiomyopathy where walls of heart ventricles become stiffened (not necessarily thickened)
21
Q
How can HHC be treated?
A
- (weekly) venesection until normal blood levels of iron return
- 500ml blood removed allowing 250mg of iron to be removed
- Tf saturation and ferritin levels are monitored
22
Q
Apart from HHC, how else can iron overload occur?
A
Multiple blood transfusions
After 20 blood transfusions, your iron levels can increase by ~5g
23
Q
What is sideroblastic anaemia and how can it be caused?
A
Ringed sideroblasts produced in bone marrow, instead of healthy RBC’s.
In these sideroblasts the iron cannot be transferred from non-haem -> haem and so remains trapped in the mitochondria of developing cells
24
Q
What is the structure of haemoglobin (Hb)?
A
4 globin monomers joined together (2 alpha and 2 beta).
4 haem groups are present = an Fe inside a porphyrin ring.
One haem group is inside each globin monomer.
25
What colour change occurs when bilirubin is oxidised?
Bilirubin is initially orange/yellow but gets oxidised to biliverdin and is then a green pigment
26
What are bile salts and what is their function?
Bile salts are DERIVED FROM PRIMARY BILE ACIDS and are important for emulsification
27
Name primary bile acids and how they are synthesised:
What special enzyme is involved?
Primary bile salts are synthesised from cholesterol and include
- > cholic acid
- > chenodeoxycholic acid
Primary bile acids are conjugated to form bile salts
- cholic acid + glycine -> glycocholic acid
- chenodeoxycholic acid + taurine -> chenodeoxytaurocholic acid
The enzyme cholesterol-7-alpha-hydroxylase is involved and when cholic acid is plentiful it inhibits this enzyme working (negative feedback).
28
How do bile salts carry out emulsification?
Are they recycled and if so how?
- bile salts have a hydrophobic portion which binds to large TAG lipid droplets and disperses them up into micelles (the hydrophilic part of bile salts prevents TAG's reforming)
- emulsification increases the SA of fats so that lipases can act
- bile salts must be RECYCLED in enterohepatic circulation as there are not enough bile salts to process all the fat in a meal
(95% bile salts recycles in enterohepatic circulation and 5% los in faeces)
- transporters move bile salts from GI tract -> intestinal capillaries -> liver (via portal vein)
- hepatocytes take up bile salts from the blood and increase bile salt secretion into canalculi
29
How is bile secretion from the GB controlled?
- sphincter of oddi is muscular ring around the duodenal papilla that controls the flow of bile and pancreatic fluid into the duodenum
- in the interdigestive period, sphincter of oddi contracted
- when sphincter is closed, increased pressure in common bile duct causes bile to flow up into GB and be concentrated (epithelial cells reabsorb water and electrolytes)
- after eating, fat in the duodenum causes CCK to be released from I cells in duodenum and jejunum
- CCK causes:
- > contraction of GB
- > relaxation of sphincter of oddi
- > reduced gastric motility
- > increased pancreatic enzyme release
- also after eating, acidic chyme in the duodenum triggers release of secretin from S cells in duodenum and jejunum
- > secretin stimulates bile production and causes liver cells to release bicarbonate into bile
- > secretin also inhibits the activity of G cells, so less gastrin = less HCl made
30
Define jaundice and its levels of biochemical markers:
- yellowish discolouration of the skin and sclerae caused by elevated levels of bilirubin in the body (hyperbilirubinaemia)
Normal total bilirubin = <21umol/l
Normal conjugated BR = <7umol/l
Jaundice total bilirubin = >30umol/l
Jaundice conjugated BR = >100umol/l
Can be classified into three groups and the proportion of UC/C BR is used to distinguish between the three groups.
31
What are the three main categories of jaundice?
Pre-hepatic
Hepatic
Post-hepatic
32
Describe pre-hepatic jaundice and its causes:
There is ELEVATED HAEMOLYSIS and the liver cannot cope with increased levels of unconjugated bilirubin.
Causes: malaria, yellow-fever, genetic disorders associated with haemolysis e.g. sickle cell anaemia
33
Describe hepatic jaundice and its causes:
Can be 3 issues:
- impaired uptake of UC bilirubin
- impaired conjugation
- impaired transport of C bilirubin into bile canaliculi
Causes: cirrhosis, hepatotoxic drugs (paracetamol overdose), viral hepatitis
34
Describe post-hepatic jaundice and its causes:
Due to OBSTRUCTION where bile cannot be released into the small intestine causing cholestasis.
Causes: hepatic/cystic/CB duct blockage due to gallstones, pancreatitis or cancerous tumour in head of pancreas.
35
Where are the three common locations that gallstones can be found?
1 - cystic bile duct -> painful as the GB contracts to try to shift the blockage
2 - common bile duct
3 - duodenal papilla
36
Describe the levels of the following pigments in their respective locations in pre/post/hepatic jaundice:
a) plasma UC BR
b) plasma C BR
c) urine C BR
d) urine urobilin
e) faeces stercobilin
(see table p8 week 2 lecture notes)
a) prehepatic = very high
hepatic = high
posthepatic = normal
b) prehepatic = high/normal
hepatic = high
posthepatic = high
c) prehepatic = normal
hepatic = high
posthepatic = high
d) prehepatic = high
hepatic = high
posthepatic = none
e) prehepatic = high
hepatic = normal
posthepatic = none
37
What is the pathophysiology of neonatal jaundice?
| How is it treated?
- common and usually harmless
- some babies livers not fully developed and have a lack of UPD glucoronyl transferase
- increased haemolysis occurs as baby's RBC have shorter lifespan of 70 days
- this along with the lack of UDP glucoronyl transferase means that not all bilirubin gets conjugated and there is a build up of UC BR
- UC BR levels build 3-5 days after birth but normally return to normal within 14 days
- if not self-limiting, then use phototherapy to treat where blue light converts the UC BR into water-soluble form that can be secreted
38
What is the pathophysiology of haemolytic disease of the newborn?
Mother is Rhesus factor +ve
- Has first baby which is Rh-ve, this baby develops normally but at birth when the mother and baby's bloods come into contact, the mother's immune system is sensitised and makes antibodies against Rh-ve
- When second baby is growing which is Rh-ve, the mothers immune system attacks it and the babies blood vessels develop abnormally
- the second child is at risk of kernicterus where bilirubin can cross the blood brain barrier and result in brain damage if not treated
39
How can you measure bile pigments in serum?
Measuring conjugated BR: add diazo reagent to serum and the conjugated bilirubin will be converted into a blue/purple derivative of bilirubin called azobilirubin (then measure absorbance of solution).
Measuring unconjugated bilirubin: it is water insoluble and so does not react with diazo reagent, so use caffeine to displace UC BR from albumin to measure total Br levels using diazo reagent (again measure absorbance).
Compare the absorbance results with graph of known values of absorbance on Y axis and bilirubin concentration on X axis.
40
What is pruritis?
Itching, which may occur due to increased bile salts in the blood.
41
How are bile pigments in urine and faeces measured?
Faeces: not measured as it is expensive and time consuming, just use visual inspection to assess is stools are pale which may suggest absence of stercobilin
Urine: dipsticks can show colour change if BR is in urine (tabs change colour)
42
Name some other ways to assess bilirubin levels in the body:
Blood gas analyses: used in some neonatal intensive care units, allows urgent BR results to be obtained within 2hrs and test is based on absorbance at 450nm of a blood sample in the presence of XS bilirubin.
Transcutaneous measurement: carried out using bilirubinometer. Measures yellowness of skin at different wavelengths to correct for variations in Hb/melanin/skin thickness.
43
What are the secretions of the exocrine pancreas and their functions?
1 - alpha amylase: digests alpha-1,4-glycosidic bonds in glycogen and starch
2 - lipase and colipase: digests lipids
3 -bicarbonate ions: neutralise gastric acid for enzyme activation
44
What is the relationship between salivary and pancreatic amylase?
Are isoenzymes (similar structures but coded for by different genes)
45
What are zymogens and name zymogens released from the pancreas?
Zymogen - an inactive precursor of an enzyme
Zymogens released that breakdown proteins:
- > chymotrypsinogen
- > procarboxypeptidase
- > trypsinogen
- > proelastase
Zymogens released that digest fats:
-> procolipase
Zymogens released that digest phospholipids:
-> prophospholipase
46
What enzyme converts trypsinogen into trypsin?
Enterokinase (enteropeptidase)
47
What is the function of trypsin?
Converts all the other zymogens into their active forms:
- chymotrypsinogen -> chymotrypsin
- procarboxypeptidase -> carboxypeptidase
- proelastase -> elastase
- procolipase -> colipase
- prophospholipase -> phospholipase
48
What is the function of amylase?
Breaks down starch into disaccharides and alpha-limit dextrins (which are then broken down by brush border enzymes including maltase, sucrase etc. into glucose and other monosaccharides).
49
Briefly describe the pathophysiology of acute pancreatitis:
- acute inflammatory condition which can be self-limiting or fatal
- pathogenesis unknown, but it is thought that some sort of pancreatic insult (from drugs/gallstones/alcohol) causes activation of zymogens before they are released from the pancreas
- these zymogens cause inflammation and destruction of the pancreas and inflammatory cytokines are released which essentially 'autodigest' the pancreas and lots of inflammation occurs
50
Briefly describe the pathophysiology of chronic pancreatitis:
- can be due to its own cause (alcohol abuse) or secondary to multiple attacks of acute pancreatitis
- irreversible pancreatic damage where there is loss of both endocrine/exocrine pancreatic function
- 90% acinar tissue lost before symptoms of malabsorption and steatorrhoea are seen
51
What are two tests that can be carried out to assess pancreatic damage?
1) serum/urine amylase
- levels will be greatly increased in pancreatitis or salivary gland swelling
2) serum lipase
- levels risen
- this test is more sensitive and specific than amylase testing
52
What tests are used to assess pancreatic function?
DIRECT TESTS = INVASIVE
INDIRECT TESTS = NON-INVASIVE
Direct:
- secretin pancreozymin test: used to measure pancreatic enzyme levels in duodenum over 2hrs
- Lundh test: measures concentrations of bicarbonate/amylase/trypsin after a meal
Indirect:
- faecal test to measure enzyme levels and elastase levels
- low elastase levels = pancreatic exocrine insufficiency
- ELISA kit used to measure faecal elastase using pipettes and a centrifuge
- immunosorbent assay then carried out with pre-coated plates of detection antibodies which will show a colour change is a specific antigen (like elastase) is present
53
What is the structure and function of the enteric NS?
- is a division of the main NS
- enteric NS functions in the interprandial period and controls reflex activity when there is a lack of input from the CNS
- is a mesh-like system of neurons that govern the function of the GI system
- made up of interstitial cells of Cajal which are found throughout GI tract in stomach, intestines and colon
- Cajal cells act as pacemakers and allow signals to propagate for contraction and peristalsis through smooth muscle
- enteric NS is influenced by:
-> vagal control (parasympathetic)
-> sympathetic control
-> various hormones
= serotonin
= motilin which STIMULATES gastric activity
= opioid receptors
54
What is the MMC and what is its function?
MMC = migrating motor complex
- functions in the interprandial period
- is waves of electrical activity that sweep through the intestines in a regular cycle during fasting and trigger peristalsis
- MMC functions in a 4-part 90 minute cycle to cleanse the stomach and intestines
- > phase 1 = prolonged quiescence
- > phase 2 = increased frequency of contractility
- > phase 3 = peak electrical and mechanical activity lasting a few minutes
- > phase 4 = declining activity back to phase 1
- MOTILIN regulates the MMC which is a polypeptide hormone produced by M cells in the small intestine
- > is secreted at 90 min intervals to coincide with the MMC
- > stimulates gastric fundus contraction and emptying
55
Name a motilin agonist:
erythromycin
56
What is gastroparesis?
Delayed gastric emptying due to poor gastro-oesophageal reflux
57
What two bowel problems can a spinal injury cause?
Describe these two problems:
Reflex bowel and flaccid bowel
Reflex bowel:
- injury to T12 or above
- anal sphincter lies shut and tonic
- reflex arc in tact but bowel will open spontaneously without any control
Flaccid bowel:
- injury to sacral nerve roots and the reflex arc is not intact
- sphincter lies open with no tone or contraction
- slow stool propagation through the colon and stool must be manually evacuated
58
What is achalasia and how is it treated?
- tight lower oesophageal sphincter that fails to relax in response to a swallow
- treat using:
- > balloon to stretch
- > laparoscopic heller's myotomy to cut cardia muscle out
- > per-oral endoscopic myotomy (specific dysfunctional muscles cut out)
59
What is oesophageal scleroderma?
- autoimmune disease with hardening of connective tissue so peristalsis is poor and LOS weak
60
What is nutcracker oesophagus?
- excessively strong peristalsis at normal rate
- is benign
- swallowing is painful and oesophagus may swell
61
What is diffuse oesophageal spasm?
- rare
- motility disorder with un-coordinated contractions of the oesophagus
- makes swallowing difficult and may cause regurgitation
62
What is accelerated gastric emptying?
What is says.
| Due to diarrhoea or dumping syndrome: common after gastric bypass surgery, food moves from stomach into SI too quickly.
63
What is chronic intestinal pseudo-obstruction?
- signs of mechanical intestinal obstruction where there isn't an obstruction
- usually a neuropathic or myopathic issue
64
What is acute colonic pseudo-obstruction/Ogilvie's syndrome?
- acute dilation of colon in absence of any mechanical obstruction
- parasympathetic disruption
65
What is Hirschprung's disease?
- a congenital condition
- blockage of LI due to poor muscle movement in the bowel as neural cells fail to migrate during colon development and the colon cannot distend or contract properly
66
What are the uses of liver function tests?
- investigate unexplained symptoms
- investigate possible liver disease
- for baseline assessment
- to monitor progression of established liver disease
- to assess response to treatment
67
What are the aminotransferases and what are their function?
AST - aspartate aminotransferase
ALT - alanine aminotransferase
- participate in gluconeogenesis by catalysing the transfer of amino acid groups from...
aspartic acid to ketoglutaric acid to make oxaloacetic acid
alanines transferred to ketoglutaric acid to make pyruvic acid
68
What are the 6 components of LFT?
```
AST
ALT
Prothrombin time (PTT)
GGT
ALP
Albumin
```
69
What is AST?
- aspartate aminotransferase
- plasma half life of 48hrs
- not specific or sensitive
70
What is ALT?
- alanine aminotransferase
- plasma half life of 18hrs
- more specific in liver disease than AST
71
What is GGT?
- gamma glutamyl transferase (an enzyme)
- transfers glutamyl groups from gamma-glutamyl peptides onto other peptides
- poor specificity
- raised in isolation after alcohol consumption as alcohol induces the enzyme (but no link between amount of alcohol/duration of intake and GGT levels)
72
What is ALP?
- alkaline phosphatase (enzyme)
- hydrolyses phosphate esters in alkaline solutions
- ALP levels rise in pregnancy, puberty and in bile duct obstruction
- increased in obstruction
73
What is albumin?
- plasma protein
- synthesised by the liver (as are all plasma proteins except immunoglobulins) so decreased level suggests liver damage
- half life of 17-21 days and is a good marker of nutrition
- can take up to 3 weeks for changes in albumin to be seen
74
What is PTT?
- measure of the rate of conversion of prothromin -> thrombin
- is a good marker of viral synthetic function of the liver
75
What do raised aminotransferases (AST and ALT) and low ALP suggest?
Hepatocellular disease or damage e.g. hepatitis
76
What do low aminotransferases (AST and ALT) and raised ALP suggest?
Cholestatic disease e.g. cholestasis is occuring due to something
77
If you suspect hepatocellular disease (high aminotransferases and low ALP) then how do you distinguish between acute or chronic hepatitis?
Chronic hepatitis = low albumin levels
| Acute hepatitis = normal albumin levels
78
If you suspect cholestatic disease (low aminotransferase levels and high ALP levels) how do you distinguish between acute and chronic cholestasis?
Chronic cholestasis = low albumin levels
Acute cholestasis = normal albumin levels
- you would then carry out ultrasound or percutaneous cholangiography to assess if the cholestasis is intrahepatic or extrahepatic
79
What would raised ALP but normal GGT suggest?
Most likely a bone disorder e.g. Paget's disease
80
What is the capacity of the bladder?
400-600ml
81
How is alcohol metabolised? (describe the pathways)
Alcohol is oxidised to produce acetaldehyde.
Acetaldehyde is then converted into acetate -> acetyl CoA -> can enter the Kreb's cycle to produce FA's
Pathway 1 - alcohol specific
- non inducible ad the main route when alcohol is not in XS
- alcohol ---(alcohol dehydrogenase)---> acetaldehyde ---(acetaldehyde dehydrogenase)---> acetate
Pathway 2 - MEOS (microsomal ethanol oxidising system)
- inducible following XS alcohol consumption
- alcohol ---(CYP2E1 enzyme)---> acetaldehyde ---> toxic metabolites
- can lead to liver damage and hepatitis
Normally the ratio between pathways 1 and 2 is 3:1
The induction of MEOS and CYP2E1 affects the metabolism of other drugs that are broken down by this pathway.
82
How can alcoholic liver disease arise?
- as alcohol is a hepatotoxin is causes liver damage in high amounts
83
What is the progression from alcoholic liver disease?
- alcohol can alter hepatocyte lipid metabolism causing STEATOSIS (fatty liver) where the lipid droplets in hepatocytes that are initially small (microvesicular) become much larger (macrovesicular)
- steatosis can develop into liver inflammation (ALCOHOLIC HEPATITIS) and then CIRRHOSIS
- cirrhosis develops in 10% alcoholics and 3-6% of these people go on to develop HEPATOCELLULAR CARCINOMA (HCC)
84
What methods are used to examine the GI tract?
endoscopy, plain X-ray, fluroscopic studies, cross sectional imaging, CT, USS, MRI
85
How is endoscopy carried out and what are its benefits?
Tube with endoscope (small camera) used to examine GI tract, allowing examination and therapeutic intervention or biopsy taking.
86
What is ERCP?
Endoscopic retrograde cholangio-pancreatography (uses endoscope to examine the pancreatic and bile ducts)
87
How is fluoroscopy carried out?
Uses radiation and requires contrast (barium)
GI tract needs to be distended with gas/air
Continuous X-ray beam then used to produce a moving X-ray movie
88
What are the benefits of USS and how would a gallstone appear?
Safe, fast, cheap, reliable
| Gallstone will appear bright, reflecting a lot of US waves back to the transducer.
89
What is CT enterography compared to a normal CT?
X-rays used in normal CT
Enterography uses a special type of IV contrast material to produce high resolution images of the SI and other structures.
90
What is a PET-CT?
Position emmision tomography and CT combined.
CT carried out but PET scanner also used to detect radioactivity emitted from the body at areas where a FDG (fluorodeoxyglucose) tracer gathers in metabolically active cells.
The images are the combined, and the brain will ALWAYS APPEAR BRIGHTER on these scans.
91
How is MRI carried out and what is MRCP?
- no radiation, uses strong magnetic fields and radiowaves
- takes longer than CT but more detailed (not good for moving structures e.g. lungs)
- cannot be used in patients with pacemakers or cerebral aneurysms
MRCP = magnetic resonance cholioangiopancreatography = special type of MRI producing detailed images of the hepatobiliary and pancreatic systems
92
What is coil embolism and when is it used?
Treatment where coiled wire is packed into a bleeding haemorrhaged vessel to act as an embolism and stop the bleeding
93
What is melana?
Black 'tarry' faeces associated with upper GI tract bleeding.
94
Define cirrhosis and some causes and clinical signs/symptoms/features:
- 3 fold definition:
- > diffuse process
- > nodule formation
- > fibrosis
- is the end result of chronic liver inflammation and scarring
- alters liver circulation and function
- hepatocytes are replaced by fibrous tissue and adipose connective tissue
- the liver has some regeneration potential if the cause is eliminated, but the liver can never fully regenerate
Causes: alcohol, viruses, drugs, inherited conditions (HCC)
Signs/symptoms: encephalopathy (confusion due to toxins in blood), sparse body hair, muscle wasting, red palms, JAUNDICE, spider angioma, ascites, hobnail liver, increased BP -> oesophageal varices and life-threatening bleeding
95
What is a xenobiotic and how does the liver handle them?
- a compound that is foreign to an organism (can be natural or man-made)
- are rarely eliminated from the body unchanged
- liver breaks down and detoxifies xenobiotics
- the liver can generate TOXIC/CARCINOGENIC METABOLITES
96
Describe endogenous fat metabolism:
- stimulated by XS cholesterol in the liver and low plasma cholesterol
- liver packages cholesterol into VLDL and FA's which are released into the blood
- in blood, LDL converts VLDL into IDL and HDL released
- IDL is taken back up by liver and converted by hepatic lipase into LDL (by removing TAG's so there is increased cholesterol concentration in the LDL)
- the LDL's are then released by the liver and taken up by tissues with LDL receptors
- if there is XS LDL in the blood then the liver increases expression of LDL receptors to lower plasma LDL levels
97
Describe exogenous fat metabolism:
- FA's and monoglycerides are absorbed in the SI
- TAG's are synthesised and packaged into chylomicrons
- chylomicrons enter lacteals and the lymphatic system and are eventually released into the bloodstream
- in the blood LPL causes FA release from chylomicrons (HDL also released) and chylomicron remnant formed
- chylomicron remnant expresses APO-E protein and liver takes up the chylomicron via APO-E receptors it expresses
- once in the liver the chylomicron remnant is broken down into FA's and cholesterol
98
How do statins work?
Increase the number of LDL receptors presented by the liver to lower plasma LDL levels
