GI and Liver Flashcards
(236 cards)
1
Q
What are the functions of the stomach?
A
- Store and mix food
- Dissolve + continue digestion
- Regulate emptying into duodenum
- Kill microbes
- Secrete intrinsic factor
- Activate proteases
- Lubrication
- Mucosal protection
- Produces chyme
2
Q
Mucous cells, parietal cells, chief cells, enterochromaffin (ECL)-like cells, G cells and D cells. What do these cells secrete? What is the function do these cells?
A
3
Q
When gastric acid (HCl) is formed, H+ ions have to enter the lumen of the stomach. Is this passive or active?
A
This is an active process. H+ ions are pumped into the lumen of the stomach from parietal cells via a H+/K+ proton pump. It is important that H+ and K+ have the same charge.
4
Q
Picture of mucous cells, parietal cells, chief cells and enteroendocrine cells.
A
5
Q
What are the two phases responsible for turning gastric acid secretion on?
A
- Cephalic phase
- Gastric phase
- Also protein in stomach. Proteins in the lumen cause pH to rise by mopping up H+ ions. This decreases somastatin secretion, which increases parietal cell activity (as somastatin inhibits parietal cells)
6
Q
What happens in the cephalic phase of turning on gastric acid secretion?
A
- Parasympathetic nervous system stimulated by sight, smell + taste of food
- Acetylcholine released. This acts directly on parietal cells + triggers release of gastrin + histamine. The net effect is increased acid production
7
Q
What happens in the gastric phase of turning on gastric acid secretion?
A
- Gastric distension, presence of amino acids + peptides
- Gastrin release. This acts directly on ECF-like + triggers the release of histamine. Histamine acts directly on parietal cells. Net effect = increased acid production
8
Q
What are the two phases involved with turning off gastric acid secretion?
A
- Gastric phase
- Intestinial phase
9
Q
What happens in the gastric phase when turning gastric acid secretion off?
A
- Low luminal pH (high H+)
- This directly inhibits gastrin secretion from G cells. This indirectly inhibits histamine secretion (via gastrin).
- This low pH stimulates stomastatin release which inhibits parietal cell activity
10
Q
What happens in the intestinial phase of turning off gastric acid secretion?
A
- In the duodenum there is:
- Distension
- Low luminal pH
- Hypertonic luminal contents
- Amino acids + fatty acids
- These factors all decrease HCl secretion via:
- Parasympathetic nerve inhibition (less ACh = less gastrin + histamine release)
- Triggering the release of enterogastrones, e.g. secretion + CKK. These inhibit gastrin release + promote somastatin release
11
Q
As a summary of gastric acid regulation, what is it regulated by?
A
- Controlled by the brain, stomach + duodenum
- 1 parasympathetic neurotransmitter (ACh)
- 1 hormone (gastrin)
- 2 paracrine factors (histamine, somatostatin)
- 2 key enterogastrones (secretin, CCK)
12
Q
What are the protective mechanisms of gastric mucosa?
A
- Alkaline mucus on luminal surface
- Tight junctions between epithelial cells
- Rapid cell replacement of damaged cells by stem cells present in base of pits
- Feedback loops for regulation of gastric acid secretion
13
Q
What is the consequence of insufficient gastric mucosa defense? What are the causes of this condition?
A
- Consequence of insufficient defense = peptic ulcers
- Causes of peptic ulcers:
- Helicobacted pylori infection (damages gastric epithelium, can be treated by 1 proton pump inhibitor + 2 antibiotics, e.g. amoxicillin)
- NSAIDs (non-steroidal anti-inflammatory drugs, inhibit cyclo-oxygenase 1 which causes reduced mucosal defense. Treated by prostaglandin analogues, e.g. misoprotol, reduced acid secretion with proton pump inhibitors or H2-receptor antagonists
- Chemical irritants, e.g. alcohol, bile salts
- Gastrinoma (tumours of G cells, secret gastrin in an unregulated way). Worth noting that G cells are enterochromaffin-like cells
14
Q
How is pepsin made? What is its role?
A
- Pepsinogen, an inactive zymogen is secreted by chief cells. This secretion is stimulated by ACh (parasympathetic)
- Pepsinogen’s secretion parallel HCl secretion from parietal cells
- Pepsinogen –> pepsin. Converted by HCl and pepsin (pepsin catalyses the reaction as it is a positive feedback loop)
- Most efficient conversion when pH < 2 (as HCl needed)
- Pepsin accounts for ~20% of protein digestion
- Pepsin increases surface area for later digestion
15
Q
What is receptive relaxation in gastric motility? What is it mediated by?
A
- Empty stomach volume = 50ml, maximum volume after eating = 1.5L. This is achieved by receptive relaxation of muscles in body + fundus of stomach
- Mediated by:
- ACh (parasympathetic - Vagus nerve)
- Nitric oxide + serotonin (releases by enteric nerves)
16
Q
What is peristalsis? How does it work?
A
- Peristalsis is a series of wave-like muscle contractions that moves food. It is produced in response to arriving food
- Ripple movement begins in body
- More powerful contraction wave in antrum
- Pyloric sphincter closes (little chyme can enter duodenum)
- Antral contents forced back to body - mixing
17
Q
What is the basic electrical rhythm for peristalsis? What cells determine the frequency of the contractions?
A
- Frequency of peristaltic waves determined by pacemaker cells called the interstitial cells of Cajal and is constant (3x per minute)
- Depolarisation waves transmitted through gap junctions to adjacent smooth muscle cells
- The strength of peristaltic waves varies (excitatory hormones + neurotransmitters further depolarise membranes, action potential generated when threshold reached)
18
Q
What increases the strength of gastric contractions?
A
- Gastrin
- Gastric distension (mediated by mechanoreceptors)
19
Q
What decreases the strength of gastric contractions?
A
- Duodenal distension
- Increase in duodenal fat
- Increase in duodenal osmolarity
- Decrease in duodenal pH
- Increased sympathetic NS stimulation
- Decreased parasympathetic NS stimulation
20
Q
Diagram of gastric emptying.
A
21
Q
What is gastroparesis? What drugs can it be caused by?
A
- Gastroparesis = delayed gastric emptying, makes people feel nauseous etc.
- Caused by:
- Gastrointestinal agents, e.g. H2 receptor antagonists, proton pump inhibitors
- Anticholinergic medications, e.g. diphenhydramine (Benadryl)
- Miscellanous, e.g. calcium channel blockers
22
Q
What are the main functions of the liver?
A
- Detoxification = filters + cleans blood of waste products
- Immune functions = fights infections + diseases
- Involved in synthesis of clotting factors, proteins, enzymes, glycogen + fats
- Production of bile + breakdown of bilirubin
- Energy storage (glycogen + fats)
- Regulation of fat metabolism
- Ability to regenerate
23
Q
The liver maintains a continuous supply of energy for the body by controlling the metabolism of what? What is the liver regulated by?
A
- Carbohydrates and fats
- Regulated by endocrine glands, e.g. pancreas. Also regulated by nerves
24
Q
What are lipids? What are triglycerides? Where can fat be stored?
A
- Lipds are esters of fatty acids + glycerol or other compounds, e.g. cholesterol. Insoluble in water and variety of structures and functions
- 90% of lipids are triglycerides, others phospholipids etc. Triglycerides = 1 glycerol molecule esterified to 3 fatty acids
- Storage areas of fat include adipocytes and hepatocytes
25
What are the two types of fatty acids?
- Saturated = line up
- Unsaturated = one or more kink
26
What are the functions of lipids?
- Energy reserve, almost all energy required is provided through oxidation or lipids, carbohydrates + proteins (liver is main storage place for glycogen)
- Part of cell membranes
- Hormone metabolism
27
Through which vessels are lipids transported to the liver?
- Portal vein
- Hepatic artery
- Lymphatics
28
In what form are lipids transported?
- Lipids are often transported as triglycerides or fatty acids bound to albumin, within lipoproteins or as chylomicron remnants
29
How are the lipids taken up into the adipocytes? What happens to the fatty acids in the adipocytes?
- Triglycerides can't diffuse through cell membranes, so lipoprotein lipase breaks down triglycerides to release free fatty acids which can diffuse through bilayer
- They can be stored + the fatty acids are re-esterified to triglycerides. Adipocytes are the main store of lipids, but hepatocytes also store some
30
How are lipids transported from adipocytes to hepatocytes?
- Hormone sensitive lipase releases free fatty acids
- Hepatic lipase enables the uptake of free fatty acids into hepatocytes
31
What happens to the lipids in the liver?
- Oxidised by the liver to produce energy when necessary
- Released as VLDL. VLDL used to transport lipids from the liver to adipose tissue. Once they reach adipose tissue, they release their triglycerides which then diffuse into adipocytes for storage
32
What are lipoproteins? What are the different types?
- Consist of a core containing TGs + cholesterol-esters. Surface layer of phospholipids, cholesterol + specific protein. Different types:
- LDL (low density lipoproteins) = formed in plasma, cholesterol delivery to all cells in body
- HDL (high density lipoproteins) = formed in liver, removes excess cholesterol from blood + tissues via excretion in bile
- VLDL (very low density lipoproteins) = synthesised in hepatocytes, triglyceride delivery from liver to adipocytes
- Chylomicron = high lipid to protein ratio + highest TG content
33
What are the effects of insulin? What happens if someone has insulin resistance?
- Promotes fat storage in adipocytes
- Stimulates lipoprotein lipase = release free fatty acids to store in adipocytes
- Insulin resistance = increased lipolysis in adipocytes leasing to increased TG in circulation. Increased fatty acids for hepatocytes to take up. Increased glucose level means lipids are less used as energy source
34
What is lipogenesis in the liver dependent on? What happens to the fatty acids formed?
- Dependent on insulin concentration + sensitivity
- Mainly for export in lipoproteins: energy source and structural component for membranes
35
Where does fatty acid beta oxidation occur in the liver? What is it proportional to?
- Occurs in the mitochondria of the hepatocytes (mitochondrial beta oxidation)
- Beta oxidation is essentially the catabolism of fatty acids to produce energy
- Each cycle shortens the fatty acid chains by 2 carbons + this continues until the fatty acid is only 2 carbons long
- Proportional to plasma levels of free fatty acids released from adipocytes
- There is also peroxisomal beta oxidation + microsomal omega oxidation
36
Before lipids reach the liver and are oxidised or released as VLDL, what happens to them?
- Emulsification of lipids by bile salts in the small intestine form micelles
- Pancreatic lipase digests lipids into free triglycerides + fatty acids which are then absorbed into the intestinal epithelial cells
- Fatty acids are combined into triglycerides and are incorporated with cholesterol into chylomicrons by SER
- These chylomicrons then exit the epithelial cells + enter lacteal system. Once these reach the circulation, the liver processes them into VLDL
37
Which of these embryological layers forms the mucosa of the gut?
Endoderm
38
Reminder of embryo development.
Green circle = mucosa of bowel
39
What else does the endoderm give rise to?
- Endoderm gives rise to epithelium of bowel. However, cells bud off from this and penetrate the mesentery to form hepatocytes of the liver + endo and exocrine cells of the pancreas
- Gut is derived from endoderm + visceral mesoderm
- Visceral mesoderm gives rise to muscle wall, connective tissue for the wall + for the pancreas and liver + visceral peritoneum. Gap on yellow = mesentery
40
Where do the foregut, midgut and hindgut start and finish? What defines these areas?
Three developmental parts of the gut:
- Foregut = starting at lower end of the hypopharynx
- Midgut = starting at the third part of the duodenum
- Hindgut= starting two thirds of the way along the transverse colon + finishing at the middle 1/3 of the anal canal
- Areas are defined by blood and nerve supply
41
What is the blood supply for the foregut, midgut and hindgut?
- Foregut = coeliac trunk/axis
- Midgut = superior mesenteric artery
- Hindgut = inferior mesenteric artery
42
What is the nerve supply to form the foregut, midgut and hindgut?
- Foregut = innervated by greater splanchnic nerve, T5-T9
- Midgut = innervated by lesser splanchnic nerve, T10-T11
- Hindgut = innervated by least splanchnic nerve, T12
43
What is referred pain?
- Pain is felt in the skin that is supplied by the same nerve roots. Usually the pain is the felt at the front rather than the whole dermatome.
T1-5 = heart and lungs, T6-9 = foregut, T10-11 = midgut + T12 = hindgut. Diagram of referred pain
44
What are the 5 stages of the development of the gut tube?
Starts with oesophagus and ends with rectum. 5 stages:
- 1 = elongation
- 2 = physiological herniation (happens simultaneously with stage 1)
- 3 = rotation
- 4 = retraction (happens simultaneously with stage 3)
- 5 = fixation
45
Diagram of elongation and herniation.
- Middle picture: blue circle = where umbilical cord is attached to embryo, so gut is going out of umbilicus into umbilical cord and coming back again = herniation. Herniation has to occur because as bowel elongates, there isn't enough room in abdomen for all developing organs
46
What happens during rotation?
- Elongated loop of midgut rotates 270 degrees in an anti-clockwise direction (rotates 90 degrees during herniation + 180 degress during return of that loop into the abdominal cavity
47
What happens in retraction?
- Week 10, herniated midgut starts to return back into abdominal cavity. The jejunum is the first part that returns back to the abdomen, the caecal bud is the last part. Fixation of the hepatic flexure of the colon + elongation of the ascending colon brings the caecum gradually to the right iliac fossa. Worth noting that the position of the appendix is variable, so appendicitis might not always present in the standard place
48
What happens in fixation?
- Some of the gut mesentery starts come to lie against the back of the abdomen + fuse into position
- These parts of the bowel are then fixed to the posterior abdominal wall with an anterior single layer of peritoneum. Now retroperitoneal. Diagram shows close up of embryo
49
Which parts of the gut are fixed?
Duodenum (except first cm which has peritoneum either side of it), ascending colon+ descending colon (and rectum). Mobile = stomach, jejunum + ileum, appendix (caecum), transverse colon and sigmoid colon
50
What are the functions of the colon?
- Absorption of water and electrolytes (vast majority of digestion occurs in small bowel, left with sloppy effluent. Water is absorbed by osmosis, sodium is actively transported)
- Production of vitamins
- Excretion of waste
51
Label this diagram of the colon.
- Ileocaecal valve connection to the terminal ileum
52
What are the layers of the colonic wall? How many stripes of longitudinal muscle are there?
- Muscular layer = continuous circular muscle. In the colon , there are 3 "stripes" of longitudinal muscle = taeniae coli
53
Picture of colon.
54
Comparison of small and large intestine.
55
Summary table of foregut, midgut and hindgut.
56
What type of epithelium does the colon contain?
Mucosa in columnar epithelium as it has a massive absorptive function. There are also goblet cells that to produce mucous for lubrication
57
What is the nerve supply to the colon?
- Extrinsic:
- Parasympathetic (vagus). This stimulates an increase in movement + secretion of mucus etc.
- Sympathetic from thoracic nerves. This stimulates the bowel to slow down
- Intrinsic:
- Meissner's and Auerbach's plexus
58
What is the gastro-colic reflex?
Stomach stretching and food in jejunum leads to a reflex which leads to mass movement of the colon
59
The lining of the rectum is columnar epithelium, just like the rest of the bowel. When does it change what type of epithelium does it change to?
- Dentate line, there is a change to squamous epithelium (where skin meets bowel)
- Important because skin sensation of squamous epithelium is sensitive
60
When the rectum is empty, what are the sphincters and puborectalis muscle like?
- Both sphincters contracted
- Puborectalis muscle contracted (maintains anorectal angle)
61
How do we know when we need the toilet?
- Rectum fills
- Reflex relaxation of internal anal sphincter. Allows anal cushions to test what is in the rectum, e.g. solid faeces
62
To complete defaecation, what contracts and relaxes?
- External sphincter relaxes
- Puborectalis relaxes, loss of anorectal angle
- Rectum contracts
- Valsalva manoeuvre (epiglottis against throat, increases pressure)
63
What is the arterial blood supply of the ascending, transverse, descending and sigmoid colon?
- Ascending = right colic artery from superior mesenteric artery
- Transverse = middle colic artery from superior mesenteric artery
- Descending = left colic artery from inferior mesenteric artery
- Sigmoid = sigmoidal arteries from inferior mesenteric artery
64
What is the venous drainage of the ascending, transverse, descending and sigmoid colon?
- Ascending = superior mesenteric vein
- Transverse = superior mesenteric vein
- Descending = inferior mesenteric vein
- Sigmoid = inferior mesenteric vein
65
What is the histology of the colon?
- All the colon looks the same
- Little folding
- No villi
- Mucosa contains closely packed crypts. Abundant goblet cells
- Muscularis externa drawn into three longitudinal bands = taeniae coli
66
What are the functions of saliva?
- Lubricant for mastication, swallowing + speech
- Maintaining oral pH - bicarbonate/carbonate buffer system, pH 6.2-7.4
- Begin starch digestion - alpha amylase
- Anti-bacterial - lysozyme
67
What two types of secretion does saliva secrete?
- Serous secretion = alpha amylase for starch digestion
- Mucus secretion = mucins for lubrication
68
Which factors affect the amount of saliva produced?
- Flow rate
- Circadian rhythm
- Type and size of gland
- Duration and type of stimulus
- Diet
- Drugs
- Age
- Gender
69
What are the 4 types of salivary glands? What do they secrete? What are they innervated by?
- Parotid = serous secretion, main source of saliva when stimulated. Not continuously active like th other glands. CN IX parasympathetic
- Sublingual = mucous secretion, CN VII parasympathetic
- Submandibular = mixed secretion, CN VII parasympathetic
- Minor glands = predominantly mucous, some serous
70
What is the most notable minor salivary gland? Why?
Von Ebner's as it is the only serous minor gland
71
What is the structure of salivary glands?
- Composed of two morphologically distinct epithelial tissue:
- Acinar cells around
- Ducts = collect to form large duct entering the mouth
72
What are the two types of acini?
- Serous acinus
- Mucous acinus
73
What does serous acinus look like? What does it secrete?
- Dark staining nucleus
- Nucleus in basal third
- Small central duct
- Secretes water + alpha amylase
74
What does mucous acinus look like? What does it secrete?
- Pale staining - "foamy"
- Nucleus at base
- Large central duct
- Secrete: mucous (water + glycoproteins)
- Found in submandibular + sublingual glands
75
Here is a picture of a salivary duct. What do the parts labelled do?
- Acini = secretory cells
- Intralobular ducts are split into intercalated + striated:
- Intercalated = connects acini to striated ducts
- Straited ducts = microvilli (highly folded), mitochondria (energy for active transport of HCO3), HCO3- and K+ secreted, Na+ and Cl- absorbed
76
What are the advantages of salivary glands?
- Well-encapsulated, limiting undesirable spread of vector
- Luminal membrane of virtually every epithelial cell in SGs are easy access in a relatively non-invasive manner
- SGs normally make large amounts of protein for export
77
What are the two general pathways for protein secretion in salivary glands?
- Predominant = leading to saliva (mucosal; across apical membrane)
- Constitutive = leading mainly towards interstitium and bloodstream (serosal; across basolateral membrane)
78
Picture of serous acini in parotid glands.
79
Picture of serous and mucous acini in submandibular glands.
80
Picture of mucous acini in sublingual gland.
81
What does the foregut consist of? What do the buds in the duodenum form? What mesenteries does the foregut have?
- Oesophagus, stomach and first half of duodenum (parts 1 + 2)
- A number of buds grow out of the duodenum during embryological development which form the pancreas, liver + biliary system
- Has two mesenteries: dorsal + ventral mesentery. Dorsal forms greater omentum, ventral forms lesser omentum
82
Summary of lateral folding.
- We end up with a foregut (green circle) connected with a mesentery (space inbetween orange lines) to upper abdomen + towards bottom, gut tube connected to anterior side of abdominal wall
83
There are 4 buds growing out of the bowel wall into the mesenteries. How many buds form the different structures?
- 2 buds form biliary system of liver. These fuse quickly so there is only one connection between the liver and biliary system + duodenum (common bile duct)
- Pancreas formed from 2 buds (one anteriorly to ventral mesentery, one posteriorly to dorsal mesentery)
(Diagram has been flipped round to give accurate representation)
84
Picture of liver growing and rotating the bowel, which pulls both the pancreas' with it.
85
The liver soon stops being the force that causes the rotation, instead it's the pancreas. Picture showing rotation due to the pancreas.
- Two pancreas' fuse together
- We end up with a liver that has a connection to the anterior abdominal wall (falciform ligament) + a bile duct entering the duodenum
86
Give a summary of the pancreas and liver formation.
- Bowel with ventral and dorsal mesentery
- Pancreas and liver growing forwards, pancreas growing backwards
- Liver starts to enlarge, pulls it to right which rotates dorsal pancreas to left side, and ventral pancreas and bile duct anti-clockwise
- The two pancreas' then fuse together. The pancreatic ducts + bile duct fuse together to drain into duodenum at same place
87
Different view of pancreas and liver formation.
Superior mesenteric vein and arteries
88
The stomach also rotates. Here is a diagram before rotation
- Greater omentum = bottom
- Lesser omentum = top
89
What happens to the liver, stomach and spleen during formation?
- Liver moves right and spleen left, rotating stomach
90
What does the liver fuse with as it enlarges?
- Liver enlarges and fused with inferior vena cava
- Behind the stomach there is a lesser sac
91
Summary. The foregut has a dorsal and ventral mesentery. What develops in the different mesenteries?
- Liver develops in ventral mesentery + spleen develops in dorsal mesentery
- Pancreas develops as a ventral + dorsal part which rotate posteriorly + fuse together
- Stomach rotates + its dorsal edge elongates to form the greater curve
- Fixation of the greater omentum + liver to the posterior wall creates a space behind the stomach (lesser sac)
92
In the GI tract, what are carbohydrates, proteins and fats broken down into?
- Carbohydrates = glucose
- Proteins = amino acids
- Fats = triglycerides
93
What happens to glucose in:
a) liver
b) muscles
c) brain
d) RBCs
e) adipocytes?
a) glucose --\> glycogen via insulin. Or glucose to acetyl coA --\> Krebs cycle --\> ATP. Acetyl coA can also form triglycerides that are released from the liver as VLDL
b) glucose --\> glycogen via insulin
c) glucose --\> acetyl coA --\> Krebs cycle --\> ATP
d) glucose --\> pyruvate. Pyruvate can also form lactate
e) glucose --\> ATP or glucose --\> triglycerides
94
What happens to amino acids?
Either form proteins, various compounds or used in a Krebs cycle to produce ATP
95
What happens to triglycerides?
Triglyceride + protein --\> chylomicrons, which enter lymphatics
96
In the fed state, what happens?
- Fuels are oxidised to energy
- Any excess is sorted (triglycerides in adipose tissue, glycogen in liver + muscle)
97
What happens when we fast?
- Blood glucose needs to be maintained, so body's stores are broken down
98
What happens to glucose in a short fast?
Glycogen stores used up, converted to glucose via glucagon = glycogenolysis
99
What happens to glucose in a long fast?
- Glycogen stores get used up, so amino acids (from muscle), lactate (from red blood cells) + glycerol (from adipocytes) are used to form glucose = gluconeogenesis
100
What happens to triglycerides during short fasting?
- Triglycerides split into fatty acids and glycerol. Fatty acids go to kidneys and muscle or form ketones in liver. Glycerol forms glucose in liver
101
What happens during prolonged fasting?
- Decreased gluconeogenesis, increased ketogenesis in liver from fatty acids (from adipocytes). Brain uses ketones much more than glucose, so remaining glucose can be used by RBCs
102
Which hormones regulate fuel metabolism?
- Growth hormone
- Somastatin
- Thyroxine
- Adrenaline
- Noradrenaline
- Cortisol
- Insulin (the only anabolic one, rest are catabolic)
- Glucagon
103
What are the effects of:
a) cortisol
b) adrenaline
c) growth hormone
d) thyroxine
on fuel metabolism?
a) lipolysis, protein breakdown, gluconeogenesis, glycogen storage
b) glycogenolysis, gluconeogenesis, lipolysis
c) gluconeogenesis, glycogen synthesis, lipolysis, protein synthesis, decreased glucose use
d) glycolysis, cholesterol synthesis, glucose uptake, protein synthesis, sensitises tissues to adrenaline
104
What are the two hormones regulating weight and appetite? What do they do?
- Leptin = in normal weight suppresses appetite, in obesity there are high leptin levels = leptin resistance
- Ghrelin = increases before meals, stimulates appetite
105
What are xenobiotics?
Xenobiotics = foreign chemicals not normally found/produced in body that cannot be used for energy requirements. Exogenous = not normally ingested, e.g. drugs. Endogenous = not foreign bodies but similar effects, e.g. bile acids, bilirubin
106
What is the aim of liver detoxification?
Liver detoxification aims to transform a substance so that it is less toxic and/or more water-soluble so that it can be excreted. Xenobiotics needed to be converted to hydrophilicity metabolites as the kidney can only excrete water-soluble compounds
107
What are the phases of liver detoxification?
- Phase 1
- Phase 2
108
What happens in phase 1?
- Phase 1 reactions:
- Transform substances from one to another via oxidation or hydrolysis reactions
- Small increase in hydrophilicity
- E.g. adding -OH or -SH groups
- E.g. cytochrome p450
109
What happens in phase 2 of detoxification?
- Conjugation (addition of a chemical group to a substance. Conjugation is important in the metabolism of bilirubin), e.g. glucuronidation (addition of glucuronic acid to a substance, make molecule hydrophilic as it is polar)
- General mechanism = polar group added to exposed group
- Results in excretion (often in bile or urine)
- Large increase in hydrophilicity
- Enzyme = non microsomal
- E.g. UDPGT. Gilbert's syndrome causes mild jaundice and is a result of inefficient UDPGT due to a genetic mutation
110
What are some common features of cytochrome-P450 enzymes?
- There are at least 10 main groups of cytochrome-P450 enzymes encoded by a superfamily of around 60 different genes (most common is CYP3A4):
- Present in SER
- Oxidise substrate + reduce oxygen
- Have a cytochrome reductive subunit which uses NADPH
- They are inducible, e.g. smoking, so increased metabolism of drugs
- They generate a reactive free radical compound
111
What is special about ethanol during detoxification?
- Metabolism of ethanol doesn't fit the category of phase 1 and phase 2
- Ethanol doesn't need to be conjugated for excretion
- Only between 2-10% is usually excreted in the urine because it is used in the liver as dietary fuel
- The major route is via alcohol dehydrogenase (ADH)
112
How is iron transported around the body?
Iron is transported around the body in plasma bound to a protein called transferrin
113
How is copper transported around the body?
Copper is transported around the body in plasma bound to a protein called ceruloplasmin
114
What does the liver store?
- Iron and copper
- Glycogen (~100g)
- Vitamins (fat soluble = A, D, E and K and one water soluble = vitamin B12)
115
For how long will these vitamins stored in the liver supply the body:
a) A
b) D
c) B12?
a) 1-2 years supply
b) 1-4 months supply
c) 3-5 years supply
116
For how long do the liver's glycogen stores last compared to the liver's lipid stores?
- Liver's glycogen stores last about 12 hours
- Liver's lipid stores last about 3 months
117
What is iron stored in the liver as? What is this protein's structure?
Iron is stored in the liver as ferritin. Ferritin is a large spherical protein with a core of up to 5000 iron atoms
118
Why do water soluble vitamins require more regular intake than fat soluble vitamins?
Because water soluble vitamins pass more readily through the body
119
What are the fat-soluble and water-soluble vitamins?
- Water-soluble = B and C
- Fat-soluble = A, D, E and K
120
What are the functions, sources and consequences of deficiency of vitamin A?
- Functions: cellular growth and differentiation, vision, lymphocyte production, skin and mucous membranes
- Sources: liver, dairy products, fruit and veg, oily fish, margarine
- Consequences of deficiency: night blindness, growth retardation, increased infection susceptibility, impaired hearing + taste
121
What are the functions, sources and consequences of deficiency of vitamin D?
- Functions = calcium absorption in gut, resorption in kidneys
- Sources = plants, mushrooms, UV light
- Consequences of deficiency = frequency bone fractures, muscle weakness, bone pain
122
What are the functions, sources and consequences of deficiency of vitamin E?
- Functions = antioxidant, protects cell walls
- Sources = nuts + seeds, vegetable oils
- Consequences of deficiency = muscle weakness, degeneration of retina
123
What are the functions, sources and consequences of deficiency of vitamin K?
- Function = formation of clotting factors of 2, 7, 9, 10 in liver
- Sources = green leafy vegetables, meat, eggs, cereals
- Consequences of deficiency = can't produce clotting factors, gum bleeding, easy bruising
124
What are the functions, sources and consequences of deficiency of vitamin C?
- Functions = collagen synthesis, antioxidant, absorption of non-haem iron
- Sources = citrus fruit, green vegetables, potatoes
- Consequences of deficiency = scurvy, bleeding gums, aching bones
125
What are the functions, sources and consequences of deficiency of vitamin B12?
- Functions = erythrocyte formation, DNA synthesis, brain development
- Sources = meat + fish, eggs, milk
- Consequences of deficiency = pernicious anaemia
126
What is folate?
- Folate is one of the B vitamins. Found in foods fortified with folic acid
127
What are amino acids the building blocks of? What is their general structure?
- Building blocks of proteins + peptides
- All amino acids a have an amino group, a carbonyl group + a carbon backbone
128
The body maintains a pool of free amino acids in the blood. What are the net contributors in the fed state and in the fasting state?
- Fed state = diet
- Fasting state = bodily protein (of which 80% is in skeletal muscle)
- Some amino acids are synthesised de novo, others are termed 'essential' as they must be found in diet
129
How many amino acids are in dipeptides, polypeptides and proteins?
- Dipeptide = 2
- Polypeptide = many, \<50
- Protein = \>50
130
What can amino acids be used for? What happens to amino acids that aren't used?
- Amino acids can bed used in protein synthesis, or lose the amino group to leave a carbon backbone for glucose synthesis and energy metabolism
- Amino acids can't be stored, so are excreted in the form of urea
131
What is nitrogen balance? What is the main source and loss of nitrogen?
- Nitrogen balance is in equilibrium when intake + output of nitrogen are roughly equal
- Main source of nitrogen is from dietary protein, main loss from gut + kidneys (as urea)
132
How is protein digested?
- Digestion starts in stomach: pepsin breaks protein chains down in smaller fragments, optimum pH 1.6 - 3.2
- In small intestine: peptides are further fragmented by pancreatic enzymes (endopeptidases), e.g. trypsin
- Final digestion to amino acids by exopeptidases: by carboxypeptidases (from pancreas) in intestinial lumen, by amino peptidases on luminal membranes of SI epithelial cells, by intracellular peptidases
- Amino acids absorbed into bloodstream
133
What do the terms glucogenic and ketogenic mean? Which two amino acids are solely ketogenic?
- Glucogenic = carbon backbone produces gluconeogenic/TCA cycle intermediates
- Ketogenic = carbon backbone produces acetyl CoA/acetoacetyl CoA
- Only leucine and lysine are solely ketogenic
134
What is transamination?
Most important part of amino acid metabolism. It is where the amino group of one amino acid is moved to an accepting alpha-ketoacid (which becomes an amino acid). For example: alanine + alpha-ketoglutarate --\> (via alanine aminotransferase) pyruvate + glutamate
135
What are the 3 types of protein produced by the liver?
- Plasma protein, e.g. albumin, fibrinogen, globulin
- Clotting proteins, e.g. clotting factors
- Complement proteins (part of innate immune response)
136
What are the 2 main functions of albumin?
- Most common plasma protein
- Maintains colloid osmotic pressure
- Binding + transporting large/hydrophobic molecules
137
Which clotting factors are produced by the liver? What are the vitamin K dependent clotting factors? What does the production of bile salts by the liver allow for?
- All clotting factors except IV + VII are produced by the liver
- Vitamin K dependent clotting factors = X, IX, VII + II (remember 1972:, 10, 9, 7, 2)
- Production of bile salts by the liver allows for the absorption of vitamin K + other fat-soluble vitamins
138
After transamination, what happens to the amino acid if it is not used to make protein or in nitrogen-containing compound synthesis?
Carbon backbone can be preserved and the nitrogenous group excreted as waste (via urea cycle)
139
What is the purpose of the glucose-alanine cycle?
- To move proteins from the muscles to the liver when glycogen stores are low
140
Draw out the glucose-alanine cycle.
- Glucose from glycogen via glucagon in liver (fasting state)
- Glycolysis in muscle to form pyruvate
- Pyruvate to alanine = transamination. This is done through ALT, glutamate donates its amino group
- Alanine forms pyruvate and NH4+ (joins urea cycle). This is again through ALT
- Pyruvate forms glucose via gluconeogenesis
141
Why is alanine aminotransferase (ALT) important clinically?
Its concentration in serum is used to measure liver health
142
What is the Cori cycle?
- Similar in function to the glucose-alanine cycle but more productive
143
Draw out the urea cycle.
- NH3 + CO2 added to ornithine --\> citrulline
- Citrulline + NH3 --\> arginine
- Arginine releases urea to regenerate ornithine. Removes toxic NH3 by creating + excreting urea
144
Why does ammonia need to be removed?
- Ammonia is neurotoxic as it can cross the blood-brain barrier + causes damage, hence why it needs to be removed
145
Which of these substances is secreted by D cells?
A. Adrenaline
B. Stomach acid
C. Somatostatin
D. Gastrin
E. Pepsinogen
C
146
Which of these substances is secreted by Enterochromaffin (ECL) Cells?
A. Amylase
B. Acetylcholine
C. Pepsinogen
D. Histamine
E. Somatostatin
D
147
Which of these substances is secreted by G cells?
A. Glycogen
B. Secretin
C. Pepsinogen
D. Somatostatin
E. Gastrin
E
148
Which of these substances is secreted by Chief cells?
A. Chymotrypsinogen
B. Somatostatin
C. Pepsinogen
D. CCK
E. Saliva
C
149
What is the function of Intrinsic Factor produced in the stomach?
A. Protects Vitamin B12 from degradation by stomach acid
B. Blocks absorption of Vitamin B12 to prevent B12 overdose
C. Allows absorption of Vitamin B12 in the terminal ileum
D. Cleaves Vitamin B6 to form Vitamin B12
E. Stimulates secretion of Vitamin B12 into the bowel lumen
C
150
How do NSAIDs irritate the stomach?
A. By decreasing chloride secretion through inhibition of the K/Cl exchange pump
B. By increasing acid secretion through stimulation of the proton pump
C. By increasing secretion of pepsinogen
D. By inhibition of gastrointestinal mucosal cyclo-oxygenase (COX) activity
E. By stimulating the vagus nerve to secrete more acetylcholine
D
151
How many layers of muscle are present in the stomach wall?
A. 3
B. 5
C. 1
D. 4
E. 2
D. Longitudinal, circular + oblique
152
What is the change in cell-type (‘metaplasia’) seen in the lower oesophagus after prolonged reflux of acid?
A. Cuboidal to columnar
B. Columnar to pseudostratified columnar
C. Columnar to stratified squamous
D. Stratified squamous to columnar
E. Pseudostratified columnar to columnar
D
153
What is the action of the proton pump on the parietal cells of the stomach?
A. K+ into cell, H+ out of cell
B. H+ into cell, K+ out of cell
C. Chloride in, HCO3- out of cell
D. H+ into cell, Chloride out of cell
E. HCO3- into cell , Chloride out of cell
A
154
You are trying to design a drug to act on histamine receptors on parietal cells to help patients with reflux disease. What would be the mechanism of this drug?
A. Inhibits Histamine 2 receptors to reduce acid secretion
B. Inhibits both Histamine 1 and Histamine 2 receptors to reduce acid secretion
C. Stimulates Histamine 1 receptors to stimulate acid secretion
D. Stimulates Histamine 2 receptors to reduce acid secretion
E. Inhibits Histamine 1 receptors to reduce acid secretion
A
155
Which of the following statements is correct regarding the function of the Vagus nerve and its action on parietal cells?
A. Vagus nerve is part of the parasympathetic system and releases histamine onto parietal cells
B. Vagus nerve is part of the sympathetic system and releases acetylcholine onto parietal cells
C. Vagus nerve is part of the parasympathetic system and releases acetylcholine onto parietal cells
D. Vagus nerve is part of the parasympathetic system and releases noradrenaline onto parietal cells
E. Vagus nerve is part of the sympathetic system and releases adrenaline onto parietal cells
C
156
Where does the Common Bile Duct drain into?
A. Caecum
B. Gallbladder
C. Stomach
D. Lesser Sac
E. Duodenum
E
157
Which of the following vessels supplies arterial blood to the Jejunum?
A. Superior Mesenteric Artery
B. Inferior Mesenteric Artery
C. Right Gastro-Epiploic Artery
D. Splenic Artery
E. Direct branches from Aorta
A
158
What is the function of the drug ‘Omeprazole’ on the GI tract?
A. Stimulation of CCK receptors to increase bile secretion
B. Direct neutralisation of stomach acid
C. Inhibit pancreatic proteases to protect lining of the duodenum
D. Blockade of Vagus nerve activity on the stomach
E. Inhibition of Proton Pump to reduce acid secretion
E
159
What is the first location that Fat is acted upon by Lipase enzymes when passing through the GI tract?
A. Duodenum
B. Oral cavity
C. Ileum
D. Oesophagus
E. Stomach
B
160
Which of the following structures is NOT present in the Porta Hepatis?
A. Left and Right Hepatic Arteries
B. Portal Vein
C. Hepatic branch of Vagus Nerve
D. Left and Right Hepatic Ducts
E. Hepatic Vein
E
161
Which of the following structures is classified in embryology as part of the ‘foregut’?
A. Gallbladder
B. Pancreas
C. Proximal 2 parts of Duodenum
D. Lower third of oesophagus
E. All of the above
E
162
What makes up our daily gut fluid balance?
163
Picture of villi and crypts.
164
How are nutrients absorbed into the blood?
Via secondary active transport
165
What is the key drive for intestinial secretion?
cAMP
166
What factors affect absorption? What factors affect secretion?
- Absorption: number and structure of enterocytes, blood and lymph flows, nutrient intake, GI motility
- Secretion: irritants, bile, bacterial toxins
- Small bowel is the main area for fluid absorption + secretion. An imbalance between absorption + secretion leads to disease
167
How are carbohydrates digested and absorbed?
- Starch in food
- Digestion begins in mouth = alpha amylase at pH 6.7
- 95% of digestion occurs in small intestine. Pancreatic alpha amylase, via pancreatic duct, breaks carbohydrates down into disaccharides, e.g. maltose
- Enzymes on luminal membranes of SI epithelial cells break down disaccharides into monosaccharides, e.g. glucose
- Monosaccharides are then absorbed into bloodstream
168
How is water absorbed?
- Water is the most abundant substance in chyme
- 8000ml of water enters the small intestine every day (in ingested food + drink and through secretions such as saliva, bile, pancreatic juices etc.)
- 80% OF WATER ABSORPTION TAKES PLACE IN THE SMALL INTESTINE. Only ~1500ml enters the large intestine. Jejunum absorbs most of the water
- 98% of the fluid load is reabsorbed, 200ml lost in stools
169
How are ions absorbed in the small intestine?
- Sodium (Na+) = active transport, co-transport with glucose, amino acids etc. Na+ absorption enhances osmotic gradient for water absorption
- Potassium (K+) = passive diffusion
- Chloride (Cl-) = active transport in exchange for bicarbonate (HCO3-). This makes the intestinal contents more alkaline
170
Which enzymes are released for digestion in the salivary glands, stomach, pancreas and intestine?
171
What are the 5 parts of the pancreas?
- Uncinate process
- Head
- Neck
- Body
- Tail
- The pancreas lies near many major abdominal blood vessels
172
What is the blood supply of the pancreas?
- Pancreatic branches of the splenic artery (body + tail)
- Superior pancreaticoduodenal artery from gastroduodenal artery (head, neck + body)
- Inferior pancreaticoduodenal artery from superior mesenteric artery (head + uncinate)
173
What is the venous drainage of the pancreas? Why do the head and uncinate have different blood supply and drainage?
- Body, neck + tail = splenic vein
- Head + uncinate = superior mesenteric artery
- Head + uncinate have a different embryological origin (ventral bud) which explains their varying blood supply + drainage
174
C
175
E
176
E
177
C
178
B
179
D
180
E
181
D
182
A
183
C
184
A
185
B
186
What are the exocrine and endocrine functions of the pancreas?
- Exocrine: acini of pancreas produce digestive enzymes, released via pancreatic duct into duodenum
- Endocrine: islet of Langerhans produce insulin, glucagon + somatostatin, large role in regulating (endocrine functions of pancreas become more important in SUGER)
187
What are the two stages that turn on enzyme secretion from the pancreas?
- Cephalic stage = innervation via vagus nerve
- Intestinal stage = secretin + cholecystokinin
188
What are the 3 substances secreted in the exocrine secretion of the pancreas?
- HCO3- (bicarbonate) = neutralises chyme in duodenum
- Zymogens (precursor enzymes) = enzymes activated in duodenum
- Digestive enzymes = involved in digestion + absorption of carbohydrates, lipids + proteins
189
What is HCO3- secretion from the pancreas stimulated by? How does it work?
- HCO3- stimulated by secretin release
- Pancreatic duct cells secrete HCO3- into the duct lumen via a Cl-/HCO3- exchanger (exocrine glands = glands that secrete substances onto an epithelial surface by way of a duct). The HCO3- comes from the breakdown of carbonic acid (H2CO3)
- The Cl- is recycled back into the lumen via a CTFR channel (in cystic fibrosis, the CTFR channels are non-functional so Cl- accumulates in the duct cells and not enough HCO3- is secreted into the duodenum)
190
What is the role of zymogens? What are they activated by?
- Zymogens exist to protect pancreatic cells from autodigestion, e.g. trysinogen, chrymotrypsinogen. For example, pepsin secreted in stomach as inactive pepsinogen to protect the cells of these secretory glands from strong protein digesting action of the enzyme
- Enterokinase is an enzyme that is key to activating zymogens
- Trypsin also plays an important role in the activation of other zymogens
191
What do the digestive enzymes pancreatic lipase, trypsin and alpha amylase digest? What are they produced by? What stimulates and inhibits the release of these enzymes?
- Pancreatic lipase = involved in digestion of lipids to free fatty acids
- Trypsin = involved in the digestion of proteins to amino acids, also activates other zymogens
- Alpha amylase = involved in the digestion of starch to maltose
- These enzymes are produced by the pancreatic acinar cells
- CCK stimulates the release of these digestive enzymes
- Somastatin inhibits the release of these digestive enzymes
192
What are the three cells involved in endocrine secretion of the pancreas? What do they secrete? Where are all these cells located?
- Alpha cells = secrete glucagon, increases blood glucose
- Beta cells = secrete insulin, decreases blood glucose
- Delta cells = secrete somastatin, inhibits pancreatic exocrine secretion as well as glucagon + insulin secretion, it also reduces gastric emptying
- These cells are all located in the Islets of Langerhans. PP cells are also present in the Islets of Langerhans + play a part in increasing pancreatic exocrine secretion
193
Bacterial enzyme hydrolysis in the gut produces this compound which is excreted in faeces:
A. Free bilirubin
B. Unconjugated bilirubin
C. Urobilinogen
D. Stercobilinogen
E. Conjugated bilirubin
D
194
Obstructive jaundice is commonly caused by gall stones within what structure?
A. Common bile duct
B. Pancreas
C. Cystic duct
D. Gall bladder
E. Right hepatic duct
A
195
What is the cause of physiological jaundice of the newborn?
A. Excess breakdown of foetal haemoglobin
B. Diversion of portal blood flow into the umbilical vein
C. Horizontal alignment of the common bile duct as it enters the duodenum
D. Immaturity of conjugation enzyme mechanisms in the liver
A
196
Microsomal enzyme uridine diphosphoglucoronosyl transferase (glucoronyl transferase) catalyses the formation of what?
A. Urobilinogen
B. Unconjugated bilirubin
C. Stercobilinogen
D. Conjugated bilirubin
E. Free bilirubin
D
197
Which of these is not a cause of obstructive jaundice?
A. Pancreatic carcinoma
B. Gilbert's syndrome
C. Cirrhosis
D. Gallstones
E. Hepatitis
B
198
What is the structure in the middle of the hepatic lobule?
A. Central vein
B. Hepatic artery
C. Bile duct
D. Portal triad
E. Portal vein
A
199
Which of the following causes an increased serum unconjugated (free) bilirubin and increased faecal urobilinogen?
A. Pre-hepatic cause of jaundice
B. Post-hepatic (obstructive) cause of jaundice
C. Mixed picture cause of jaundice
D. None of the above
E. Hepatocellular cause of jaundice
A
200
Which of these is not a function of the liver?
A. Storing vitamins A D E K
B. Glycogen storage
C. Production of urobilinogen
D. Production of cholesterol
E. Conversion of thyroxine (T4) into triiodothyronine (T3)
C
201
Which of the following statements is true?
A. The sympathetic nervous system releases acetylcholine causing the gallbladder to contract
B. Cholecystokinin is released in response to the presence of carbohydrates in the gut
C. The gallbladder synthesises 50mls of bile per day
D. Cholecystokinin is released in response to the presence of amino acids in the gut
E. The entero-pancreatic reflex is mediated by the sympathetic system
D
202
Which compound is returned to the liver by the enterohepatic circulation?
A. Stercobilinogen
B. Conjugated bilirubin
C. Unconjugated bilirubin
D. Free bilirubin
E. Urobilinogen
E
203
Which one of these cells is part of the reticuloendothelial system in the liver?
A. Hepatocyte
B. Ito cell (hepatic stellate cell)
C. Fibroblast
D. Sinusoidal endothelial cell
E. Kupffer cell
E
204
Which of the following statements is false?
A. The acinus is the functional hepatic unit
B. The liver lies in the right hypochondrium
C. The liver is divided into 8 segments
D. The hepatic blood supply is 35-40% of the cardiac output
E. The portal vein supplies 75% of hepatic blood flow
D
205
Considering the function of the pancreas, which of the following is false?
A. Glucagon stimulates the breakdown of glycogen
B. Pancreatic polypeptide is secreted by the F islet cell
C. Somatostatin is secreted by the gamma (G) islet cells
D. Glucagon is secreted by the alpha (A) islet cells
E. Insulin is secreted by the beta (B) islet cells
C
206
What structure is situated within the duodenal loop?
A. Gallbladder
B. Right hepatic duct
C. Common bile duct
D. Cystic duct
E. Pancreas
E
207
Where are fat soluble vitamins absorbed? Where are water soluble vitamins absorbed?
- Fat soluble vitamins (A, D, E and K) are absorbed along with fat (in micelles) = ileum
- Water soluble vitamins (B and C) = jejunum except B12 = terminal ileum
208
What are the two stomach sphincters?
Cardiac sphincter and pyloric sphincter
209
What does the rugae of the stomach help with?
Rugae on inner surface helps digest food
210
The stomach is supplied by branches of what?
Coeliac trunk
211
What are the 3 muscles in the abdominal wall?
- External oblique (fibres run inferomedially, function = contra lateral rotation of the torso)
- Internal oblique (fibres run superomedially, function = bilateral contraction compresses the abdomen + unilateral contraction ipsilaterally rotates the torso)
- Transversus abdominus (function = compression of abdomen)
212
What do the 3 muscles in the abdominal wall form?
An aponeurosis
213
What is the arcuate line?
The demarcation where the internal oblique + transversus abdominis aponeuroses of the rectus sheath start to pass anteriorly to the rectus abdominis muscle, leaving only the transversalis fascia posteriorly
214
Above the arcuate line, what lies in front and behind?
- In front = superior oblique, some of internal oblique
- Behind = some of internal oblique, transversus abdominis
215
Below the arcuate line, what lies in front and behind?
- All fascia lies in front
- Only peritoneum + transversalis fascia behind rectus abdominis here
216
How do you calculate Body Mass Index (BMI)?
Weight/(height)^2 = kg/m^2
217
How is vitamin B12 absorbed?
- B12 is a very large + charged vitamin
- Ingested orally
- Intrinsic factor produced by parietal cells in stomach
- B12 binds to intrinsic factor
- Intrinsic factor binds to specific sites on epithelial cells in terminal ileum
- B12 absorbed by endocytosis
218
What is Glisson's capsule?
A fibrous capsule that surrounds the liver
219
What are the six ligaments of the liver?
- Right triangular
- Left triangular
- Coronary ligament
- Falciform ligament
- Ligamentum teres (main remnant of umbilical vein)
- Ligamentum venosum (remnant of ductus venosum which made blood bypass the liver in the foetus)
220
In which way to blood and bile flow in the liver?
Opposite direction
221
What is the blood supply to the gallbladder?
- Cystic artery (usually a branch of the right hepatic artery)
- Occassionally, a cystic vein is present which drains blood from the gallbladder into the portal vein
222
Where is the gallbladder located?
Underneath the right 9th costal cartilage in the midclavicular line, it also lies on the transpyloric plane of Addison
223
What are the sphincter of Oddi and the ampulla of Vater?
- Sphincter of Oddi is located at the terminal end of common bile duct where it drains into the duodenum from the major duodenal papilla (in the second part of the duodenum)
- Ampulla of Vater is a swelling where the pancreatic duct + common bile duct coalesce
224
What do the terms retroperitoneal and intraperitoneal mean?
- Retroperitoneal = covered by parietal peritoneum on its anterior surface
- Intraperitoneal = covered by visceral peritoneum both anteriorly + posteriorly
225
Bile is secreted continuously by hepatocytes. Where is it sorted and concentrated, what is it used for, and why is it released?
- Bile is stored + concentrated in the gallbladder
- Bile is used to emulsify fats as well as an excretory pathway
- Released in response to an increase in fatty acid concentration in the duodenum, via CCK secretion
226
What are the constituents of bile?
- Cholesterol
- Lecithin (a phospholipid)
- HCO3-
- Bile acids
- Bile pigment, e.g. bilirubin
227
Give the pathway of bile from the hepatocytes to expulsion from the gallbladder.
- After bile is produced by hepatocytes, it travels to the gallbladder via the common hepatic duct
- Once in the gallbladder, it is stored and concentrated
- Once CCK is released by duodenal I cells, it causes the gallbladder to contract
- This causes bile to be expelled into the cystic duct + then into the common bile duct
- Bile is then used to aid the emulsification of lipids
228
How is bilirubin metabolised?
- RBCs that are old/damaged are ingested by macrophages
- Their haemoglobin is broken down into haem + globin. Globin is used to generate new RBCs in bone marrow, haem is broken down into biliverdin + iron via haem oxygenase -
- Iron recycled, biliverdin by biliverdin reductase to form unconjugated bilirubin. This is toxic + lipid-soluble so must be metabolised + excreted
- Unconjugated bilirubin is then transported to the liver by binding to albumin
- Once in the liver, unconjugated bilirubin undergoes glucurodination by glucuronyl transferase. This forms conjugated bilirubin, which is soluble so dissolves into bile + enters biliary system
- Bile enters the duodenum via the sphincter of Oddi and eventually reaches terminal ileum. It aids the absorption of lipids + fat-soluble vitamins through its course
- Bile reduced by bacteria into urobilinogen (lipid-soluble so can be reabsorbed)
- About 80% of urobilinogen is further oxidised to stercobilin which is excreted in faeces (partly responsible for the colour of faeces)
- Around 20% of urobilinogen is reabsorbed into the bloodstream and goes to the liver where some is recycled for bile production, while a small percentage reaches the kidneys = oxidised further into urobilin + excreted into the urine
229
What is jaundice? What are the three types?
Discolouration of skin due to high serum bilirubin. 3 types:
- Pre-hepatic = increased haemolysis = increased unconjugated bilirubin
- Hepatic jaundice = caused by liver impairment, causes decreased ability of the liver to conjugate bilirubin
- Post-hepatic jaundice = caused by blockage of bile ducts = backflow of conjugated bilirubin into blood
230
What happens if the cholesterol concentration is too high relative to phospholipids in bile?
It will crystallise out of solution + form gallstones, these can become lodged in the common bile duct or cystic duct
231
1. Which salivary gland has a mainly serous secretion and which nerve innervated this gland?
2. Which cells secrete pepsinogen?
3. What percentage of water absorption takes place in the small intestine?
4. Which molecule gives urine its yellow colour?
5. What is the main enzyme involved in Phase 1 detoxification reactions?
6. The uncinate process arises from which bud of the embryological pancreas?
1. Parotid gland, CN IX (glossopharyngeal)
2. Chief cells
3. 80%
4. Urobilin
5. Cytochrome P450
6. Ventral bud
232
Where does the sympathetic chain run from and to?
T2 to L1
233
Comparison of the small intestine vs large intestine.
234
Comparison of jejunum vs ileum.
235
1. Name three external unique features of the colon
2. Name 2 factors that decrease the strength of gastric contractions
3. How does the arterial supply of the jejunum compare to the ileum?
1. Haustrations, taenia coli, appendices epiploicae
2. Duodenal distension, increase in duodenal fat (could also have increase in duodenal osmolarity, decrease in duodenal pH, increased sympathetic NS stimulation and decreased parasympathetic NS stimulation
3. Jejunum = long arteries, few vasa recta; ileum = short arteries, many vasa recta
236
