Alimentary System Flashcards
(598 cards)
1
Q
What is digestion?
A
Break down of macromolecules to allow absorption (physical or enzymatic)
2
Q
What is absorption?
A
Moving nutrient and water across a membrane
3
Q
What are the components of the GI tract?
A
Mouth Oesophagus Stomach Liver (gall bladder) Duodenum Jejunum Ileum Colon Appendix Anus
4
Q
What are the names of the salivary glands?
A
Sublingual gland
Parotid gland
Submandibular gland
5
Q
What are the general symptoms of GI disease?
A
Anorexia
Weight loss
Anaemia
6
Q
What is koilnychia?
A
Spooning of the nails
7
Q
What is leuconychia?
A
Whitening of the nails
8
Q
What is the biggest cause of disease in UK from a GI disease?
A
Liver cirrhosis
9
Q
What proportion of hospital admissions are due to GI disease?
A
1/8
10
Q
What are the major GI diseases worldwide?
A
1) Malnutrition
2) Enteric infections
3) Viral hepatitis and consequences
4) Gastric cancer
11
Q
What are the major GI diseases in the UK?
A
1) Dyspepsia (indigestion)
2) Liver disease (due to alcohol and obesity)
3) Colon cancer
12
Q
What are the main causes of abnormal liver function tests in the UK?
A
1) Chronic Hep B
2) Chronic Hep C
3) Alcohol-related steato-hepatitis
4) Obesity-related steato-hepatitis
13
Q
What is Barrett’s oesophagus?
A
Where the squamous-cell epithelium of the oesophagus mucosa is replaced by metastatic columnar cells
14
Q
What is the prevalence of gall stones? Who is most likely to suffer?
A
1/10
Middle-ages overweight women
15
Q
What is the main cause of chronic pancreatitis?
A
Alcoholism
16
Q
What is normally present in acute pancreatitis?
A
Ethanol accumulation and gallstones
17
Q
How many people are affected by IBS?
A
1/3
18
Q
What is the basic structure of the gut wall?
A
- Epithelium
- Lamina propria
- Muscularis mucosae
- Submucosa
- Muscularis
- Serosa / Adventitia
19
Q
What is the lamina propria and what is contained in this layer?
A
Connective tissue containing capillaries, nerve endings etc
20
Q
What are the submucosa and muscularis and what is contained in these layers?
A
Submucosa: Connective tissue
Muscularis: Smooth muscle
Both contain nerve plexus
21
Q
What spinal levels does the oesophagus start and pass through the diaphragm?
A
Starts C5
End T10
22
Q
What nerves are at risk during oesophageal surgery?
A
Recurrent laryngeal nerve
23
Q
What epithelia make up the oesophagus lining?
A
Stratified squamous epithelia
24
Q
What sphincters are present in the oesophagus and where are they? When are they open?
A
Upper oesophageal sphincter at the top
Lower oesophageal sphincter near the stomach
Permanently closed. Opened by the brain by active swallowing.
Upper closes as soon as food passes
Lower open for the whole duration of swallowing
25
What type of muscle is the upper oesophageal sphincter
Skeletal
26
What type of muscle is the lower oesophageal sphincter
Skeletal and smooth muscle
27
How does the peristalsis wave move food down the oesophagus?
Muscle above the food bolus is contracting and the muscle below is relaxing which pushes the food down the oesophagus.
Can have secondary wave if food does not pass down the first time
GRAVITY HAS NO IMPACT!
28
What is the gastro-oesophageal junction? How is acid reflux prevented at this point
The point where the oesophagus joins the stomach. Once swallowing reflex has passed the skeletal muscle of the diaphragm, the circular muscle of the lower oesophagus closes so food can't pass back into the oesophagus. This is helped by the fact that the stomach is below the diaphragm so the pressure either side of the sphincter is equal. Less likely to get reflux
(Negative pressure above the diaphragm)
29
Why do you get bad acid reflux when pregnant?
Pushes stomach up so oesophagus only above the diaphragm where there is negative pressure. Pressure difference either side of the sphincter means acid reflux is more likely
30
What is the epithelial transition in the oesophagus? At what point does the transition occur>
Oesophagus has stratified squamous (abrasion)
Stomach has simple columnar (secretory)
Transition occurs at the zigzag line (Z) line
31
What are the folds of the stomach called? What is their purpose?
Rugae
Allows stomach volume to change drastically
Allows it to expand and contract
32
How does the process of belching occur?
You initiate a swallowing reflex which allows the air to escape
33
What is the function of the stomach?
Break down food into smaller particles stored (due to acid and pepsin); hold food and release at a controlled steady rate into duodenum; kill parasites and certain bacteria.
34
Where does mucus secretion occur in the stomach?
In the fundus, cardia, body and pyloric region
35
Other than mucus secretion, what occurs in the body and the fundus of the stomach?
HCl and pepsinogen secretion
36
What occurs in the antrum of the stomach?
Gastrin secretion
37
How does the stomach maintain a highly acidic concentration without it burning through the stomach lining?
Cells produce mucus which acts as a gel coating. They produce HCO3- which gets trapped in the mucus and neutralises acid
38
How much acid does the stomach produce?
2L/day
39
What is the pH of the epithelial lining and the stomach lumen?
Epithelial lining= 6-7
| Stomach lumen= 1-2
40
What is the gastric chief cell? What does it produce?
Protein secreting epithelial cell with an abundant RER
Golgi packaging and modified for export
Masses of apical secretion granules
Secretes pepsinogen
41
What is the gastric parietal cell? What components contribute to H+ production? What is it's structure?
Main acid producing cell in the body
Has many mitochondria which requires a lot of ATP, cytoplasmic tubulovesicles which contain H+/K+ ATPase and internal canaliculi which extend to the apical surface
When it switches to the active secreting state tubulovesicles fuse with membrane and microvilli project into canaliculi leading out into the lumen of the stomach.
42
How does a parietal cell produce H+?
1) Carbonic anhydrase converts H2O+CO2 to HCO3- and H+
2) Na+/K+ exchange in interstitial fluid/capillaries and then in stomach lumen (K+ into cell, into lumen)
3) HCO3- is exchanged for Cl- (Cl- into cell into lumen)
4) Mitochondria produce lots of ATP
5) H+/K+ ATPase exchange = lots of H+ in lumen)
43
How would inhibition of carbonic anhydrase influence acid secretion in the stomach?
It would decrease acid secretion
44
What is pepsinogen? How is it activated?
A inactive precursor.
An acidic environment causes a conformational change causing enzymatic activity within pepsinogen molecules, cleaving themselves to produce peptin
45
What does peptin digest?
Protein
| The hardest thing to digest
46
What is gastrin? What does it do?
At very high pH gastrin secretion is suppressed (when stomach is empty)
When you eat protein stomach acid concentration drops which stimulates gastrin release. Gastrin stimulates acid secretion which in turn activates pepsin.
It can also stimulate histamine release from chromaffin cells (lamina propia) and histamine is also a powerful stimulus for acid secretion
47
What are the three phases of gastric secretion?
1) Cephalic phase
2) Gastric phase
3) Intestinal phase
48
What is the cephalic phase of gastric secretion?
The thought, sight, smell and taste of food activates the brain to have an effect on the stomach.
The vagus nerve (parasympathetic) is activated. Acetylcholine acts on chromaffin cells to stimulate secretion of histamine or acts directly on parietal cells.
49
What is the gastric phase of gastric secretion?
When food is in the stomach stretch (stretch receptors) stimulates the brain to initiate gastric secretion (production of more acid) via the vagus nerve (parasympathetic nerve)
The stretch is also detected by the enteric nervous system which also responds by initiating gastric secretions.
Chemoreceptors detect the chemical change in the gut have an effect (trigger) on gastrin secretion
50
What is the intestinal phase of gastric secretion?
Largely inhibitory
If pH is low or nutrients present signals sent to brian to switch off gastrin secretion
Enterogastric reflex: Low pH in chyme causes hormone production:
- Gastric inhibitory peptide
- Cholecystokinin
- Secretin
which pass via the blood back to stomach to switch off acid production
If there is undigested protein STIMULATION of gastrin
51
What are the enterogastrones?
Gastric inhibitory peptide
Cholecystokinin
Secretin
52
What is the excitatory component of the intestinal phase of gastric secretion?
Depends on the protein concentration in the duodenum.
If your stomach hasn't effectively broken down the protein (high [protein] entering the SI) there is a stimulation of gastrin to increase acid production
53
What are two types of drug that would decrease acid secretion in the stomach?
1) Omeprazole: proton pump inhibitor, block H+/K+ ATPase pump
2) Ranitidine: Histamine receptor antagonist- blocks histamine receptor and prevents stimulation of acid secretion
54
What is the size of the SI and the size of each of the parts?
Approximately 6m long and 3.5cm in diamter
Duodenum: 25cm
Jejunum: 2.5m
Ileum: 3.75m
55
What is the mesentery?
Throws the SI into folds and supports the blood supply to the SI
56
What is the basic structure of the small intestine?
External wall has longitudinal and circular muscles (important for motility
Internal mucosa arranged in circular folds and is covered in villi (∼1mm tall)
Has invaginations known as Crypts of Lieberkuhn
57
What are villi? Where are they found? What is their structure?
Only occur in the small intestine. They are motile and have a rich blood supply and lymph drainage for absorption or digested nutrients. They also have a good innervation from the submucosal plexus.
Villi have simple epithelium (1 cell thick), dominated by enterocytes (columnar absorptive cells)
58
What cell type makes up the mucosa in the SI?
1) Primarily enterocytes (absorptive cells)
2) Scattered goblet cells
3) Enteroendocrine cells
59
What cells are found in the Crypts of Lieberkuhn?
1) Paneth cells
| 2) Stem cells
60
What are enterocytes? What is their function? What is their lifespan?
The most abundant cells in the SI. Tall columnar cells with microvilli and a basal nucleus
Specialised for absorption and transport of substances.
Short lifespan of 1-6 days
61
What are the functions of tight junctions in enterocytes?
Stops things moving between gaps in between cells. Also stops proteins in the phospholipid bilayer moving to different parts of the cell
62
What are microvilli? How many are there per cell? What if found on the surface of microvilli?
They make up the brush border (∼0.5-1.5μm high) (1/1000 a size of villi)
Several thousand microvilli per cell
Surface of microvilli is covered with glycocalyx
63
What is glycocalyx?
A rich carbohydrate layer on apical membrane that serves as protection from digestional lumen, yet it allows for absorption. It traps a layer of water and mucous known as the unstirred layer, which regulates the rate of absorption from the intestinal lumen
64
How big is the surface area of the small intestine?
Cylindrical internal surface area is 0.4m²
The volli and microvilli increase the surface area to ∼200m²
500 fold increase
65
What is the second most abundant cell type in the SI?
Goblet cells
66
What are enteroendocrine cells in the SI? What cell type are they? What is their role?
Columnar epithelial cells, scattered among the absorptive cells. Mostly found in the lower part of the crypts.
Hormone secreting (e.g. to influence gut motility)
a.k.a. Chromaffin cells
67
What are Paneth cells? What do they secrete? What are their roles?
Found only in the bases of the crypts. Contan large acidophilic granules containing:
- antibacterial enzyme lysozyme (protects stem cells)
- glycoproteins, and zinc (essential trace metal for a number of enzymes)
Also engulf some bacteria and protozoa
May have a role in regulating intestinal flora
68
What is the life span of cells in the epithelium of the SI?
Enterocytes and goblet cells have a short life span (about 36 hours)
Continually replaced by dividing stem cells in the crypts
Migrate up the villi and shed
69
What are the stem cells in the SI
Undifferentiated cells which remain capable of cell division to replace cells which die.
They are ESSENTIAL to continually replenish the GI surface epithelium
Continually divide by mitosis
Migrate up to top of villus, replacing older cells that die by apoptosis. At villus tips cells become senescent, sloughed into lumen and are digested and reabsorbed
Differentiate into various cell types (pluripotent)
70
Why is the lifespan of epithelial cells in the SI so short in comparison to other tissues?
Enterocytes are the first line of defence against GI pathogens and may be directly affected by toxic substances in the diet.
Effects of agents which interfere with cell function, metabolic rate etc will be diminished. Any lesions will be short-lived
71
How does cholera infect a host?
The cholera enterotoxin results in prolonged opening of the chloride channels in the SI allowing uncontrolled secretion of water
Bodily fluid moves freely into the lumen and out, leading to rapid, massive dehydration and death
Treatment is rehydration. Cholera bacteria will clear as epithelium is replaced.
72
What characteristics are unique to the duodenum?
Distinguished by the presence of Brunner's glands
- Submucosal coiled tubular mucous glands secreting alkaline fluid
- Open into the base of the crypts
Alkaline secretions:
- Neutralises acidic chyme from the stomach, protecting the proximal SI
- Help optimise pH for action of pancreatic digestive enzymes
73
What characteristic are unique to the jejunum?
Characterised by the presence of numerous, large folds in the submucosa, called plicae circulares (or valves of Kerckring)
Also present in the duodenum and ileum but plicae in the jejunum tend to be taller, thinner and more frequent
74
What characteristics are unique to the ileum?
Shares some of the features with the large intestine
Has lots of Peyer's patches (large clusters of lymph nodules in the submucosa)
Prime immune system against intestinal bacteria (bactericidal Paneth cells, rapid cell turnover)
Well positioned to prevent bacteria from colon migrating up to small intestine
75
What are the different cell types in the SI and their brief function?
```
Enterocytes
- Absorption (most abundant)
Goblet cells
- mucous secreting
Enteroendocrine cells
- hormone secreting
Paneth cells
- antibacterial, protect stem cells
Stem cells
- cell turnover, pluripotent
```
76
What are the three functions of motility in the SI?
1) To mix ingested food with digestive secretions and enzymes
2) To facilitate contact between contents of intestine and the intestinal mucose
3) To propel intestinal contents along alimentary tract
77
What is segmentation?
MIXES the contents of the lumen
Segmentation occurs by stationary contraction of circular muscles at intervals
More frequent contractions in duodenum compared to ileum- allow pancreatic enzymes and bile to mix with chyme
Although chyme moves in both directions, net effect is movement towards the colon
78
What is peristalsis?
Involved sequential contraction of adjacent rings of smooth muslce
Propels chyme towards the colon
Most waves of peristalsis travel about 10cm (not the full length of the intestine)
Segmentation and peristalsis result in chyme being segmented, mixed and propelled towards the colon
79
What is the migrating motor complex?
In fasting = cycles of smooth muscle contractions
Each cycle = contraction of adjacent segments of small intestine
Begin in stomach, migrate through small intestine towards colon. On reaching terminal ileum, next contraction starts in the duodenum
Prevents migration of colonic bacteria into the ileum and may 'clean' the intestine of residual food
Also occurs in the fed state- but less ordered and less frequent
80
What sphincter lies between the stomach and the duodenum?
Pyloric sphincter
81
What sphincter lies between the bile/ pancreatic duct and the duodenum?
Sphincter of Oddi
| Hepatopancreatic sphincter
82
How do digestive enzymes and bile enter the duodenum?
Through the bile duct and pancreatic duct
83
How does digestion occur in the duodenum?
1) Bile and digestive enzymes enter the duodenum
2) Duodenal epithelium also produces its own digestive enzymes
Digestion occurs both in the lumen and in contact with the membrane
84
What type of absorption doesn't use carrier proteins?
Passive diffusion
85
What type of absorption does require carrier proteins but does not require energy?
Facilitated diffusion
86
What type of absorption uses hydrolysis of ATP to move substances against the concentration gradient using a carrier protein?
Primary active transport
87
What type of absorption uses the electrochemical gradient to move substances against the concentration gradient using a carrier protein?
Secondary active transport
88
How and where does digestion of carbohydrates occur?
Digestion begins in the mouth by salivary α-amylase, but α-amylase is destroyed in the stomach (acid pH)
Most of the digestion of carbohydrates occurs in the small intestine
After being broken down by salivary and pancreatic α-amylase the products and simple carbohydrate digestion occurs at the membrane
Monosaccharides are absorbed into enterocytes
89
What is pancreatic α-amylase? When is it secreted?
Secreted in the duodenum in response to a meal
Continues digestion of starch and glycogen in the SI (started by salivary amylase)
Needs Cl- for optimum activity and neutral/slightly alkaline pH (Brunner's glands in duodenum= alkaline secretion)
Acts mainly in the lumen (some also absorbed into brush border)
90
How are glucose and galactose absorbed? What is the carrier protein?
By secondary active transport (carrier protein and electrochemical gradient)
Carrier protein= SGLT-1 on apical membrane
91
How is fructose absorbed? What is the carrier protein?
```
Facilitated diffusion (carrier protein, no energy required)
Carrier protein= GLUT-5 on apical membrane
```
92
What is better absorped? Glucose or fructose? Why?
Glucose? Uses energy for absorption unlike fructose which uses facilitated diffusion
93
What carrier protein facilitates movement of glucose across the basolateral membrane in the SI?
GLUT-2
94
How are proteins digested?
Begins in the stomach by pepsin, but this is inactivated by the alkaline duodenum
Pancreatic proteases are secreted as precursors
Trypsinogen is activated by enterokinase (duodenum) to trypsin, an enzyme located on the duodenal brush border
Trypsin then activates the other proteases (e.g. chymotrypsin, elastase)
95
Where is enterokinase found? What does it do?
In the duodenum
| Activates trypsinogen to form trypsin
96
How are proteins absorbed?
Brush border peptidases break down the larger peptides prior to absorption.
Amino acids are absorbed by facilitated diffusion and secondary active transport (similar to sugars)
Di- and tri- peptides are absorbed using carrier proteins distinct from single amino acids
Cytoplasmic peptidases break down most of the di- and tri- peptides before they cross the basolateral membrane
97
How are lipids digested?
Lipids are poorly soluble in water. Four stage process in the SI:
1) Secretion of bile and lipases
2) Emulsification
3) Enzymatic hydrolysis of ester linkages
4) Solubization of lipolytic products in bile salt micelles
98
How does bile emulsification occur?
Bile and lipase are secreted into the duodenum. Bile salts facilitate the emulsification of fat inot suspension of lipid droplet (∼1μm diameter)
The function of emulsification is to increase the surface area for digestion. Allows pancreatic lipase to split triglycerides (into two fatty acids and a monoglyceride at fat/water interface)
99
What is the structure of a bile acid?
Amphipathic
Steroid nucleus planar- two faces
- Hydrophobic (nucleus and methyl) face dissolves in fat
- Hydrophobic (hydroxyl and carboxyl) face dissolves in water
100
What are bile salt micelles? What is their function?
Hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic tail regoins in the micelles centre
Mixed micelles in small intestine = water insoluble monoglycerides from lipolysis are solubised by forming a core, stabilised by bile salts
101
What is the function of lipase? How does it work?
Lipase breaks down triglycerides into monoglycerides and free fatty acids.
It need to form a complex with colipase to work.
Colipase prevents bile salts from displacing lipase from the fat droplet
102
What are the lipid digestion enzymes?
1) Lipase (colipase)
2) Phospholipase A2
3) Pancreatic cholesterol esterase
103
What is the function of phospholipase A2?
Hydrolyses fatty acids at the 2 position in many phospholipids, resulting in lysophospholipids and free fatty acids
104
What is the function of pancreatic cholesterol esterase?
Hydrolyses cholesterol ester to free cholesterol and fatty acid
105
How are lipids absorbed in the SI?
Micelles are important in absorption- they are absorbed much quicker than an emulsion
Micelles allow transport across the unstirred layer, and present the fatty acids and monoglycerides to the brush border
The whole micelle is not absorbed together- bile salts are absorbed in the ileum, but lipid absorption is usually complete by the middle of the jejunum
Bile salts are transported back to the liver for recycling (enterohepatic circulation)
106
What happens to lipids once they have been absorbed by enterocytes?
They are resynthesised into triglycerides
107
What are the two different pathways that resynthesise triglycerides in enterocytes after they have been absorbed?
1) Monoglyceride acylation pathway (MAJOR)
| 2) Phosphatidic acid pathway (minor)
108
What is the monoglyceride acylation pathway?
Fatty acids bind to the apical membrane
Fatty acid binding proteins (FABP) facilitate transfer of fatty acids from apical membrane to the smooth ER
In the smooth ER fatty acids are esterified into diglycerides and triglycerides
109
What is the phosphatidic acid pathway?
Triglycerides are synthesised from CoA fatty acid and α-glycerophosphate
110
How are lipoproteins transported in the body?
In chylomicrons
111
How are chylomicrons produced? Where are they transported?
Lipoprotein particles are synthesised in enterocytes as an emulsion
80-90% triglycerides, 8-9% phospholipids, 2% cholesterol, 2% protein, trace carbohydrate
Chylomicrons are transported to the Golgi and secreted across the basement membrane by exocytosis
Too big to enter blood capillaries of villi so enter lacteals (lymph channels)
112
What is the function of the ileocaecal sphincter?
Separates the ileum and the colon
Relaxation and contraction controls the passage of material into the colon
Also prevents the back flow of bacteria into the ileum
113
Paneth cells
1) Are found at the villus tip
2) Secrete mucous
3) Contain acidophilic granules
4) Are pluripotent
5) Secrete enterokinase
3) Contain acidophilic granules
114
What ligament runs down the middle of the liver?
Falciform ligament
115
What are the four lobes of the liver?
Right lobe
Caudate lobe
Quadrate lobe
Left lobe
116
During liver development what parts of the embryo form the respective cells of the liver?
Endoderm: parenchymal cells
Mesoderm: connective tissue
117
What is the process of development of the liver?
∼29 days: Hepatic diverticulum of liver bud development (diverticulum invades septum transversum). Cell differentiation
∼30 days: Septum transversum forming liver stroma. Hepatic diverticulum forming hepatic trabeculae
∼32 days: Epithelial cord proliferation enmeshing stromal capillaries
∼33 days: Enlargement of the liver bud. Haematopoietic function appears
∼44 days: Bile ducts become reorganised (continuity between liver cells and gut)
∼44-56 days: Biliary ductules developed in periportal connective tissue and ductal plates form that receive biliary canaliculi
118
How many days into development is the liver bud first apparent? What Carnegie stage?
∼29 days
| Carnagie stage 11
119
After how many weeks of development has the pancreas migrated to the posterior, left portion of the abdominal cavity/ coelom?
8 weeks
120
After how many weeks of development has the liver rotated round towards the right?
10 weeks
121
How much of cardiac output goes to the liver?
25%
122
What type of blood supply does the liver have? Wha vessels supply and drain it?
Dual blood supply
20% arterial blood from the hepatic arteries (left and right branches)
80% venous blood draining from the gut through the hepatic portal vein
Blood drains into the inferior vena cava via the hepatic vein
123
How many segments make up the liver?
8 segments
124
What is the Couinaud classification?
The dividing of the liver into 8 segments
125
What is the significance of the liver segments?
They each have their own blood supply. They can be resected without damaging those remaining
126
What liver segment is the caudate lobe?
Segment 1
127
What segments are on the far left side of the liver? Which is superior and which is inferior?
Superior 2
| Inferior 3
128
What segments are next to segments 2 and 3 in the liver (superior and inferior)?
Superior 4a
| Inferior b
129
What lobes are on the far right of the liver? Which is superior and which is inferior?
Superior 7
| Inferior 6
130
What segments are next to segments 6 and 7 in the liver (superior and inferior)?
Superior 8
| Inferior 5
131
What are the different cell types in the liver? What is their brief function?
```
1) Hepatocytes
80%
2) Endothelial cells
Lining blood vessels and sinusoids
3) Cholangiocytes (bile duct epithelial cells)
Lining biliary structures
4) Kupffer cells
Fixed phagocytes (liver macrophages)
5) Hepatic stellate cells
Vitamin A storage cells (Ito cells) may be activated to a fibrogenic myofibroblastic phenotype
```
132
What cell would have a flattened, dense cell nuclei that appears to be in the sinusoids?
```
Kupffer cell (in hepatic sinusoid) OR
Hepatic stellate cell (next to hepatocytes)
```
133
What do hepatic cells radiate around?
A central vein
134
What is the function of hepatic stellate cells in the liver?
Vitamin A storage
| Activation=ECM production (fibrogenesis)
135
What is the function of sinusoidal endothelial cells in the liver?
Fenestrated- allows lipid and other large molecule movement to and from hepatocytes
136
What is the function of Kupffer cells in the liver?
Phagocytosis (including RBC break down)
| Secretion of cytokines that promote HSC activation- proliferation, contraction and fibrogenesis
137
What is a liver lobule comprised of?
```
6 portal triad
- Bile duct
- Branch of hepatic portal vein
- Branch of hepatic artery
Flowing to the central canal which leaves the liver forming a hexagonal structure
```
138
Where are the portal tracts in the liver?
Around the adjoining lobules
139
What are portal tracts comprised of?
1) An arteriole
2) A branch of the portal vein
3) A bile duct
140
What vessels supply the liver and where does the blood flow?
Deoxygenated nutrient rich blood from the portal vein
Oxygenated blood from the hepatic artery
Flows towards the central vein
141
What is an acinus in the liver?
A functional unit between two central veins and two portal triads.
Divided into zones dependent on proximity to arterial blood supply
3- Closest to central vein
2- In between 1 and 3
1- In between the two portal triad
142
Which zone in an acinus is most susceptible to ischaemia?
Zone 3
143
Which zone in an acinus is most susceptible to viral hepatitis?
Zone 1
144
What cells produce bile, how do they get to the bile duct and in what direction?
Hepatocytes produce bile
| Flows along the canaliculus to the bile duct in the opposite direction to blood flow
145
What are the functions of the liver?
1) Protein metabolism
2) Carbohydrate metabolism
3) Lipid metabolism
4) Detoxification
146
How is the liver involved in protein synthesis and metabolism?
RER: synthesis of non-essential amino acids, albumin, clotting factors etc
Golgi apparatus: packaging for secretion
Deamination of amino acids: amino group to urea cycle (cycle enzymes situated in cytoplas of hepatocyte. Carbon skeleton reused (glucose and lipid metabolism
147
How is the liver involved in carbohydrate metabolism?
Has SER, mitochondria and cytoplasmic enzymes
- Glycolysis: glucose oxidation to form ATP and pyruvate (pyruvate→Kreb's cycle→more ATP)
- Glycogenesis: storage of excess glucose as glycogen
- Glycogenolysis: breakdown of glycogen to glucose
- Gluconeogenesis: de novo synthesis of glucose
148
How is the liver involved in lipid metabolism?
Has SER, peroxisomes and mitochondria
- Triglyceride metabolism: synthesis of fatty acids converted to triglycerides and lipoproteins for transport to cells requireing energy (FA β-oxidation). Digested triglyceride chylomicron remnants processed into lipoproteins (including cholersterol)
- Bile acid (+Na=salt) production
149
How is the liver involved in detoxification?
Has lysosomes and SER
| Metabolises, modifies/ detoxifies endogenous compounds e.g. drugs
150
How does the gall bladder and cystic duct develop? How far into embryogenesis does this occur?
∼4 weeks: The hepatic bud (diverticulum) divides in the pars hepatica and pars cystica.
∼8 weeks: The pars cystica develops into the gall bladder and cystic duct
151
From hepatocytes what vessels does bile travel through to reach the gall bladder?
```
Hepatocytes
Bile canaliculi
Interlobular bile ducts
Right/left hepatic ducts
Common hepatic duct
Cystic ducts
Gallbladder
```
152
From the gall bladder what is bile transported through to reach the small intestine?
Gallbladder
Common bile duct
Ampulla vater
Small intestine
153
What functions does the liver have a key role in?
Digestion
Biosynthesis
Energy metabolism
Degradation / Detoxification
154
Where is glucose stored as glycogen?
In the liver and in muscles
155
How long can liver glycogen stores last? How much is there?
```
24 hours (fasting)
80g
```
156
What is the Cori cycle?
```
Method of recycling lactate from muscle (to the liver) and made into glucose (then back to muscle)
Muscle:
Glucose→2Pyruvate (2ATP)
2 Pyruvate⇌2Lactate
Liver:
2Lactate⇌2Pyruvate
2Pyruvate (+6ATP)→Glucose
```
157
What reactions occur during gluconeogenesis?
The Cori cycle
| Deamination of amino acids
158
How does deamination of amino acids produce glucose?
Alanine→Pyruvate→Glucose
or from triglycerides:
Triglycerides→Glycerol→Glucose
159
How many calories are produced from carbohydrate and fat?
Carbohydrate: 120kcal per mole oxygen
Fat: 100kcal per mole oxygen
160
How much protein is synthesised by the liver per day?
90% of plasma proteins
| 15-50g/day
161
What proteins does the liver synthesise?
Plasma proteins- binding/carrier proteins, plasma COP- oedema
Blood clotting factors
Dietary "non-essential" amino acids by transamination
162
What occurs in a transamination reaction?
The exchange of an amine group from an amino acid to a keto-acid
163
Why is gluatamic acid important?
It is an important intermediate for essential amino acids which do not have appropriate keto acid precursors
It is the end product of many transamination reactions
164
Where and how does deamination occur?
```
Muscle:
Glucose→2Pyruvate (2ATP)
2Pyruvate→2Alanine (transamination)
(α-amino acid→α-keto acid)
2Alanine transported to liver:
2Alanine→2Pyruvate (deamination)
NH₃ (+4ATP) →Urea
2Pyruvate (+6ATP)→Glucose
```
165
What happens to the NH₃ produced in the deamination reaction?
NH₃ is highly toxic (particularly to the CNS) so it is converted to urea
2NH₃ + CO₂ (+4ATP) → Urea + H₂O
Urea is very water soluble, metabolically inert, non-toxic. It is excreted in the urine
166
How does the liver metabolise fat?
Fat main energy store in the body (100xglycogen). When glycogen stores are full the liver can convert glucose and amino acids to fat for storage
1) Converts FAs to acetyl CoA (TCA cycle)
2) Converts acetyl coA to acetoacetate for transport in the blood to other tissues where it can produce energy
3) Synthesises lipoproteins, cholesterol and phospholipids
167
Where is fat stored in the body?
In adipose tissue and the liver
168
What is the process of fat metabolism?
Fat is stored as triglyceride, broken down to fatty acids and transported to the liver.
In mitochondria they undergo β-oxidation to produce Acetyl-CoA and then enter the TCA cycle or produce ketone bodies
169
What hormones stimulate break down of triglycerides into fatty acids!
Glucagon
Adrenaline
Glucocorticoids
170
How are fatty acids transported to the liver?
Bound to albumin
171
Why are ketone bodies produced during fat metabolism?
To provide energy for the brain and extrahepatic tissue
172
What ketone bodies are produced to provide energy for tissues?
Acetoacetate
| 3HMG-CoA
173
What enzyme converts ketone bodies to a usable source? Where is this NOT found?
Thiophorase
| Not found in the liver
174
Why are lipids converted into lipoproteins?
To allow them to be transported in the blood as they are normally hydrophobic
175
How can triglyceride reach the liver? (From what sources?)
1) From adipose tissue- converted to NEFAs then fatty acids then triglycerides
2) Directly from the diet as sugars which can be converted to new fatty acids then triglycerides
3) From the gut, via chylomicrons which can be converted to triglycerides
176
What does the liver produce from triglycerides to allow easy transport in the blood?
(Lipoprotein synthesis)
VLDLs (Very low denisity lipoproteins)
| Converted to VLDL TAG which can be converted to fatty acids
177
What is the content of VLDLs?
Large amount of triglycerides
178
What is the content of LDL?
High cholesterol and phospholipid (causes atherosclerosis)
179
What is the content of HDL?
High protein content
180
What is the largest lipoprotein? (to smallest?)
VLDL
IDL
LDL
HDL
181
What is cholesterol used for?
Used in synthesis of various compounds including steroid hormones and bile salts
182
How much bile is stored in the gall bladder?
15-60ml
183
What is bile made up of?
```
Bile salts (50% dry weight)
Cholesterol
Phospholipids (lecithin)
Bile pigments (bilirubin, biliverdin)
Bicarbonate ions
Water
```
184
How is bile produced?
Cholesterol (addition of carboxyl and hydroxyl groups)
(Chenodeoxy) Cholic acid (primary bile acid) (Conjugation with taurine or glycine)
Bile acid conjugates transported to gall bladder
Secreted into duodenum (Bacteria in the ileum deconjugate and dehydroxylate primary bile salts to form secondary bile salts
185
What is the primary bile acid?
(Chenodeoxy) cholic acid
186
What is the function of bile?
Digestion/absorption or fats
Excretion variety substances via GI tract
Neutralise acid chyme from stomach
187
When is bile secreted?
Released into duodenum during digestion. Small amounts during cephalic phase, gastic phases due to vagus nerve and gastrin
Intestinal phase, cholecystikinin causes contraction of gall bladder and relaxation of sphincter of Oddi
188
How does bile assist in the digestion and absorption of fats?
Lipids are poorly soluble in water which makes them more complicated to digest
1) Secretion of bile and lipases
2) Emulsification (by bile salts)
3) Enzymatic hydrolysis of ester linkages between lipids
4) Solubization of lipolytic products in bile salt micelles
189
What is the process of enterohepatic recirculation?
Active reabsorption of bile salts in terminal ileum. In addition, deconjugation and de-hydroxylation by bacteria make bile salt lipid soluble.
Recirculate via hepatic portal vein back to the liver. Hepatocytes avidly extract bile salts- one pass clears all
Bile salts are reconjugated and sone rehydroxylated before reuse
190
How much bile salts are actually lost (not taken into enterohepatic recirculation)?
191
How many times is the bile salt pool secreted per meal?
Twice
192
How is bile involved in excretion of substances via the GI tract?
Liver breaks down or inactivated steroid and peptide hormones. They are then secreted into bile for excretion
Also performs similar role with variety of "foreign" compounds- usually drugs
Excretory route for excess cholesterol- lecithin allows more cholesterol in micelles.
Excretion of bile pigments. Bilirubin from breakdown of haem from old erythrocytes.
Porphyrin group reduced to bilirubin and conjugated to glucoronic acid in liver
193
What can cause gall stones?
Too much cholesterol
| Liver disease- bile pigment gall stones
194
Where is iron from old erythrocytes removed and conserved?
In the spleen
195
What is stored in the liver? How long do they last?
Fat soluble vitamins- A, D, E → 6-12 months (K but small store as used constantly for clotting factors)
Storage of iron as ferritin (available for erythropoiesis)
Storage od vitamin B₁₂- pernicious (megaloblastic) anaemia, nerve demyelination
Glycogen and fat stores
196
What vitamin has very small stores due to frequent use to produce clotting factors?
Vitamin K
197
How is iron stored in the liver?
As ferratin
198
What is a deficiency in vitamin B₁₂ associated with?
Pernicious anaemia
| Nerve demyelination
199
How is the liver involved in protection?
Liver sinusoids contain Kupffer cells (macrophages). Bacteria may cross from gut lumen into blood. Kupffer cells destroy these and prevent bacteria entering the rest of the body
200
How is the liver involved in Ca²⁺ metabolism?
UV light converts cholesterol to vitamin D precursor, which requires a double hydroxylation to convert it to the active form. First is in the liver, second is in the kidneys
201
Where does the first hydroxylation of cholesterol to produce vitamin D occur?
Liver
202
Where does the second hydroxylation of cholesterol to produce vitamin D occur?
Kidney
203
What disease affecting the liver present with low calcium?
Rickets
204
How does the pancreas develop?
A foregut derivative arises at the foregut-midgut junction
Dorsal and ventral buds form. The ventral bud is part of the hepatobiliary bud
The duodenum rotates to form a C shape, the ventral bud swings round to lie adjacent to the dorsal bud, and both buds fuse
The ventral bud becomes the main pancreatic duct
205
What are the different sections of the pancreas?
```
Uncinate (hook like)
Head
Neck
Body
Tail
```
206
Where are islets most abundant in the pancreas?
In the tail
207
Where is the pancreas located n the body?
Lies mainly on the posterior abdominal wall extending from C-shaped duodenum to hilum of the spleen
Main posterior relations are IVC, abdominal aorta and left kidney
208
Where does the pancreas get it's blood supply?
From the coeliac and superior mesenteric arteries
209
What are the endocrine functions of the pancreas?
Secreting into the blood stream to have an effect on distant target organs
210
What are the exocrine functions of the pancreas?
Secretion into a duct to have a direct local effect
211
What are the main endocrine secretions of the pancreas?
Insulin
Glucagon
Somatostatin: Endocrine cyanide
212
What is the function of insulin?
Anabolic hormone, promotes glucose transport into cells and storage as glycogon, reduces blood glucose, promotes protein synthesis and lipogenesis
213
What is the function of glucagon?
Increases gluconeogenesis and glycogenolysis
214
What is the function of somatostatin?
Inhibits the action of most hormones and physiological processes
215
How much of the pancreas is involved in endocrine and exocrine function?
Endocrine: 2%
Exocrine: 98%
216
Describe the endocrine function of the pancreas
Islets of Langerhans secrete hormones into the blood- insulin and glucagon (also somatostatin and pancreatic polypeptide). Regulates blood glucose, metabolism and growth effects
217
Describe the exocrine functions of the pancreas
Secretes pancreatic juice into duodenum via pancreatic duct/common bile duct.
Digestive function
218
If you have pancreatic disease what part of pancreatic function would be affected?
Both endocrine and exocrine
219
What cells are involved in exocrine function of the pancreas?
Acini: grape like clusters of secretory units (into ducts)
| Acinar cells secrete pro-enzymes into ducts
220
How do the endocrine cells connect to the duct system of the pancreas?
They are derived from the branching duct system but they lose contact with the ducts and become islets.
They differentiate into α- and β-cells secreting into the blood
221
What is the composition of each cell type in the islets?
β-cells: 60-70% → insulin
α-cells: 15-20% → glucagon
δ-cells: 5-10% → somatostatin
Islets are highly vascular ensuring all endocrine cells have close access to a site for secretion
222
What are the type cell types involved in the production of pancreatic juice?
1) Acinar cell (blind ends C)
2) Duct cell (ducts =)
C======
223
What are the two components of pancreatic juice?
Bicarbonate
| Enzyme
224
What component of pancreatic juice do acinar cells produce?
Low volume, viscous, enzyme-rich component
225
What component of pancreatic juice do duct and centroacinar cells produce?
High volume, watery, HCO₃⁻-rich component
226
Describe the bicarbonate component of pancreatic juice?
Produced by duct and centroacinar cells.
It is rich in bicarbonate ∼120mM (pH 7.5-8.0)
Neutralises acid chyme from the stomach
- prevents damage to duodenal mucosa
- raises pH to optimum range for pancreatic enzymes to work
Washes low volume enzyme secretion out of pancreas and into duodenum
227
Why does bicarbonate secretion stop when the pH of chyme is ∼5 (still acidic)?
Bile also contains bicarbonate and help neutralise the acid chyme
Also Brunner's glands (in small intestine) also secrete alkaline fluid
228
How is HCO₃⁻ produced in the pancreas?
1) CO₂ diffuses into duct cells and reacts with water (catalysed by carbonic anhydrase) to produce HCO₃⁻ and H⁺
2) HCO₃⁻ is then pumped into the lumen (HCO₃⁻/Cl⁻ exchanger)
3) H⁺ pumped into blood, exchanged with Na⁺
4) Na⁺K⁺ATPase pumps Na⁺ back into the blood and K⁺ into the duct cell
5) K⁺ channel returns K⁺ to blood
6) Cl⁻ returns to the lumen via Cl⁻-channel
7) Na⁺ moves down the gradient via paracellular ("tight" junctions). H₂O follows
229
How does cystic fibrosis cause pancreatic dysfunction?
Cl⁻-channel is dysfunctional, so you get a concentrated pancreatic juice
230
How does the production of juice in the stomach and the pancreas relate?
In the stomach: H⁺ goes into gastric juice and HCO₃⁻ into the blood. Gastric venous blood is alkaline
In the pancreas: HCO₃⁻ goes into pancreatic juice and H⁺ into the blood. Pancreatic venous blood is acidic
231
What enzymes are produced for fat, protein and carbohydrate digestion and where are they stored in the pancreas?
Fat: lipases
Protein: Proteases
Carbohydrate: Amylase
Synthesised and stored in zymogen granules
232
What are zymogens?
Pro-enzymes
| Inactive form of an enzyme
233
How are pancreatic enzymes released to prevent auto-digestion?
Proteases are released as inactive pro-enzymes to protect acini and ducts.
Pancreas also contains a trypsin inhibitor to prevent trypsin activation
Enzymes are only activated in the duodenum
234
What problem arises from blockage of pancreatic duct?
May overload protections and result in auto-digestion
| Acute pancreatitis
235
What does enterokinase do? Where is it secreted?
Converts trypsinogen to trypsin
| Secreted by duodenal mucosa
236
What is the function of trypsin?
Activated enzymes in pancreatic juice
237
Lipase is secreted in it's active form. What prevents lipase from initiating auto-digestion?
Requires the presence of colipase which is secreted as a precursor
Also requires the presence of bile salts
238
What causes altered pancreatic enzyme secretion?
Pancreatic secretion adapt to diet (e.g. high protein, low carbs = ↑ proportion of proteases, ↓ proportion of amylases)
239
What is the mechanism of Orlistat?
Inhibits pancreatic lipases- prevents lipid digestion therefore can't absorb it and causes steatorrhoea
240
What causes steatorrhoea?
Cystic fibrosis
Chronic pancreatitis
Orlistat
241
What nerve innervates the gut (to brain)
Vagus nerve
242
What pancreatic secretion occurs in the cephalic phase?
Enzyme-rich component only
| Low volume- "mobilises" enzymes
243
In what phase does most of the pancreatic secretion occur?
Intestinal phase (70-80%)
244
What pancreatic secretion occurs in the gastric phase?
Stimulation of pancreatic secretion originating from food arriving in the stomach
Same mechanisms involved as for cephalic phase
245
What pancreatic secretion occurs in the intestinal phase?
70-80% of pancreatic secretion
Hormonally mediated when gastric chyme enters duodenum
BOTH components of pancreatic juice stimulated (enzymes + HCO₃⁻-juice flows into duodenum)
246
What hormone controls the secretions of bicarbonate from the pancreas into the duodenum?
Secretin (cAMP)
247
What hormone controls the secretions of enzyme from the pancreas into the duodenum?
Cholecystokinin (CCK) (Ca²⁺/PLC)
248
What does cholecystokinin stimulate the secretion of?
Enzyme component of pancreatic juice
| Bile secretion
249
What is the mechanism of bicarbonate secretion from the pancreas into the duodenum?
1) Acidic chyme from stomach enters duodenum
2) H⁺ in chyme stimulates S-cells to release secretin into the blood
3) Reaches pancreas and binds to receptors on pancreatic duct cells
4) Stimulates pancreas to release HCO₃⁻ into duct and into duodenum
5) pH in duodenal lumen increases- switching off secretin
250
What is the mechanism of enzyme secretion from the pancrease into the duodenum?
1) Chyme from stomach enters duodenum
2) Peptides and fat bind to receptors on C-cells cells stimulating a release of CCK
3) CCK binds to receptors on acinar cells (or stimulated by ACh from vagus nerve)
4) Acinar cells release proenzymes and trypsinogen
251
How do you switch your CCK system off?
1) Cephalic phase ends when meal is eaten
| 2) Absorption of fats and peptides removes local lumiinal stimulus for CCK release from mucosa
252
How does the release of CCK and secretin interact?
CCK alone→ no effect on bicarbonate
Secretin alone→ no effect on enzyme secretion
CCK+Secretin→ CCK can markedly increase bicarbonate secretion that has been stimulated by secretin
253
What is the mechanism of digestion from the stomach to duodenum?
1) Food mixed, digested in the stomach (pH=2)
2) Chyme squirted into duodenum
3) H⁺ ions in duodenum stimulate release of secretin stimulating release of pancreatic juice (plus bile and Brunner's gland secretion) to rise pH to neutral/alkaline
4) Peptides + fat in duodenum cause sharp rise in CCK, vagal nerve, stimulating pancreatic enzyme release, peaks by 30mins, continues until stomach empty
5) CCK potentiates effects of secretin on aqueous component (necessary because most of duodenum not at low pH)
254
Does trypsin convert lipase to pro-lipase?
No. Lipase is secreted in it's active form but requires co-lipase
255
How are protons pumped into the blood from duct cells?
Secondary active transport
256
What is primary active transport?
Directly uses metabolic energy to transport molecules across a membrane
e.g. Na⁺K⁺ATPase
257
What is secondary active transport?
Co-transport
| Does not use ATP but relies on the electrochemical gradient created by pumping ions in/out of the cell
258
What is the cecum?
A blind pouch just distal to the ileocecal valve
259
Where is the appendix?
A thin finger-like extension of the cecum
260
What are the function of the colon?
Reabsorption of electrolytes and water
| Elimination of undigested food and waste
261
How big is the colon?
1.5m long
| 6cm in diameter
262
What is the structure of the colon?
```
Ascending colon
Hepatic flexure
Transverse colon
Splenic flexure
Descending colon
Sigmoid colon
Rectum
Anal canal
```
263
What organs are supplied by the celiac artery?
Liver
Stomach
Pancreas
Spleen
264
What organs are supplied by the superior mesenteric artery?
Pancreas
Small intestine
2/3 of colon
265
What organs are supplied by the inferior mesenteric artery?
Distal third of colon
266
What artery specifically supplies the proximal transverse colon?
Middle colic artery (branch of superior mesenteric)
267
What are the fatty tags on the peritoneum around the colon called?
Epiplocae
268
What are the thick longitudinal bands of muscle around the colon called? How many are there?
Taenia coli
| 3
269
What are the nodules of lymphatic tissue in the distal small intestine called?
Peyer's patches
270
What are the nodules of lymphoid tissue in the colon called?
Solitary nodules
271
What is the function of taenia coli?
Intestinal motility
272
What are the pouched ovoid segments in the colon called?
Haustra
273
Where does most of the absorption occur in the colon?
Most in the proximal colon
274
How much water is reabsorbed in the colon?
∼1.5L
| can absorb ∼4.5
275
What is the rectum?
Dilated distal portion of the alimentary canal.
Similar histology to the colon but distinguished by transverse rectal folds in its submucosa and the absence of taenia coli
276
What type of muscle is the internal sphincter in the anal canal?
Circular muscle
277
What type of muscle is the external sphincter in the anal canal?
Striated muscle
278
What similarities with the small intestine does the colon have?
Enterocytes and goblet cells are abundant
| Abundant crypts containing stem cells
279
How does the mucosa in the colon differ from the small intestine?
Smooth because there are no villi
| Enterocytes have short, irregular microvilli and primarily concerned with resorption of salts
280
Are there more goblet cells in the colon or small intestine?
Colon
281
What is the function of goblet cells in the colon? Where are they found?
More prevalent in the crypts than along the surface, number increases distally toward the rectum
Mucus facilitates the passage of the increasingly solid colonic contents, and covers bacteria and particulate matter
282
What stimulates secretion from goblet cells in the colon?
Acetylcholine (from the parasympathetic and enteric nervous system)
283
What is the dominant cell type in crypts in the colon?
Goblet cells
284
Where are there more enteroendocrine cells? In the colon or in the small intestine?
In the small intestine
285
What cell type is present in the small intestine but not in the colon?
Paneth cells
286
How is glycocalyx different in the colon to the glycocalyx in the small intestine?
In the colon the glycocalyx does not contain the digestive enzymes of that in the small intestine
287
How do the taenia coli and circular layers of muscle relate?
Bundle of muscle from the taenia coli penetrate the circular layer at irregular intervals
288
What are colonic contractions?
Kneading process which is minimally propulsive- 5-10cm/hr at most
Promotes absorption of electrolytes and water
289
What type of contractions occur in the proximal colon? Why?
Antipropulsive patterns dominate to retain chyme
290
What type of contractions occur in the transverse and descending colon?
Haustral contractions (localised segmental contractions of circular muscle) cause back and forth mixing
291
How ofter do short propulsive movements occur in the colon? When do they increase in frequency?
Every 30 minutes
| Increase in frequency following a meal
292
What is a mass movement in the colon? When do they occur?
Occurs 1-3 times daily
| Resembles a peristaltic wave that can propel contents 1/3-3/4 of the length of the large intestine in a few seconds
293
How does fibre effect transport of food through the colon?
Food that contains fibre (indigestible material) promotes rapid transport through the colon
294
What nerves of the parasympathetic nervous system innervate the colon?
Vagus nerve: Ascending colon and most of the transverse colon
Pelvic nerve: More distal colon
295
What part of the sympathetic nervous system innervates the colon?
Lower thoracic and upper lumbar spinal cord
296
What nerves of the somatic nervous system control the external anal sphincter?
Pudendal nerves
297
What is Hirschsprung's disease?
No enteric intramural ganglia
298
The defecation reflex is controlled primarily by what part of the spinal cord?
Sacral spinal cord
299
What is the mechanism of defecation?
1) Reflex to sudden distension of walls of rectum
2) Pressure receptors send signals via myenteric plexus to initiate peristaltic waves in descending colon, sigmoid colon and rectum. Internal anal sphincter is inhibited
3) Weak intrinsic signal augmented by autonomic reflex
4) External anal sphincter is under voluntary control
5) Urge resisted, sensation subsides
300
How much faeces is passed per day? What is the composition?
```
150g/day (adult)
Two thirds water
Solids: cellulose, bacteria, cell debris, bile pigments, salts (K⁺)
Bile pigments give colour
Bacterial fermentation gives odour
```
301
What gives faeces it's colour?
Bilirubin
302
What part of the gut contains flora?
Colon
| NOT stomach or small intestine
303
How much live bacteria is present in the body?
1.5kg
304
What are the roles of intestinal flora?
1) Synthesise and excrete vitamins (e.g. Vitamin K- sterile animals have clotting problems)
2) Prevent colonisation of pathogens by competing for attachment sites or for essential nutrients
3) Antagonise other bacteria through the production of substances which inhibit or kill non-indigenous species
4) Stimulate the production of cross-reactive antibodies. Antibodies produced against components of the normal flora can cross react with certain related pathogens and thereby prevent infection or invasion
5) Stimulate the development of certain tissues, including cecum and lymphatic tissues
6) Fibre can be broken down by colonic bacteria to produce short chain fatty acids which can regulate gut hormone release, or be absorbed to be used as an energy source or to influence functions such as food intake or insulin sensitivity directly
305
What is the most prevalent bacteria in the colon?
Bacteroides
Gram negative, anaerobic, non-sporeforming bacteria
Implicated in the initiation of colitis and colon cancer
306
What types of bacteria is bifidobacteria? Why is it important in the colonisation of the colon?
Gram-positive, non-sporeforming, lactic acid bacteria.
| Thought to prevent colonisation by potential pathogens
307
What is paracellular transport?
Transport from apical to basal side through tight junctions and lateral intercellular spaces
308
What is transcellular transport?
Transport from apical to basal side through the epithelial cells
309
What is the purpose of a channel protein?
Forms an aqueous pore in the membrane allowing specific solutes to pass across
310
What is the purpose of a carrier protein?
Binds to the solute and undergoes a conformational change to transport it across the membrane
311
Which method of transport across a membrane is quicker? Channel protein or carrier protein?
Channel protein
312
What can be used to "gate" (initiate opening or closing) of ion channels?
1) Voltage-gated
2) Ligand-gated (extracellular ligand)
3) Ligand-gated (intracellular ligand)
4) Mechanically gated
313
What are the different types of carrier-mediated transport?
1) Uniport
2) Symport (coupled transport)
3) Antiport (coupled transport)
314
What is facilitated diffusion?
Enhances the rate a substance can flow down its concentration gradient.
Tends to equilibrate the substance across the membrane and does not require energy
315
Give an example of primary active transport
Na⁺K⁺ATPase
| H⁺K⁺ATPase
316
Give an example of secondary active transport
SGLT-1 co-transporter
HCO₃⁻Cl⁻ counter transport
Na⁺H⁺ counter transport
317
Give an example of facilitated transporters
GLUT-5
| GLUT-2
318
How are glucose and galactose absorbed into enterocytes? On what carrier protein does this occur?
Secondary active transport using the energy from Na⁺ to also carry the sugar
SGLT-1
319
How is fructose absorbed? On what carrier protein does this occur? Why?
Facilitated diffusion
GLUT-5
This is effective at low concentrations of fructose in the lumen as there are low tissue and plasma levels
320
How is glucose transported from enterocytes into the interstitium? What carrier protein conducts this?
Facilitated diffusion
| GLUT-2 - high capacity, low affinity transporter
321
Where is the vast majority of water in the GI tract absorbed?
In the jejunum
322
Where does all the fluid reabsorbed in the intestines originate? What are the volumes?
```
Ingest: 2L
Saliva: 1.2L
Gastric secretions: 2L
Bile: 0.7L
Pancreas: 1.2L
Intestinal: 2.4L
```
323
How much fluid does the small intestine and colon reabsorb per day?
SI: 8L
Colon: 1.4L
324
What is the mechanism of standing gradient osmosis?
1) Na pumped into enterocyte from intestinal lumen
2) Na⁺ pumped into intracellular space via Na⁺K⁺ATPase
3) Cl⁻ and HCO₃⁻ also pumped into intracellular space due electrical potential from Na⁺
4) Creates hypertonic intracellular space
5) Water moves into hypertonic intracellular space
6) Creates hydrostatic pressure
7) Water and ions then move into the blood
325
How is Na⁺ transported from gut lumen into enterocytes in the proximal bowel?
Counter-transport in exchange for H⁺
326
How is Na⁺ transported from gut lumen into enterocytes in the jejunum?
Co-transport with amino acids, monosaccharides
327
How is Na⁺ transported from gut lumen into enterocytes in the ileum?
Co-transport with Cl
328
How is Na⁺ transported from gut lumen into enterocytes in the colon?
Restricted movement through ion channels
329
Where does potassium exhibit paracellular transport? In which direction?
Small intestine: into blood
| Colon: into lumen
330
Where is Ca²⁺ reabsorbed?
In the duodenum and ileum
331
How much calcium is secreted and absorbed each day?
Secreted: 0.6g
Absorbed: 0.7g
332
What vitamins and hormones stimulate absorption of calcium in the gut?
Vitamin D
| Parathyroid hormone
333
What is the mechanism of calcium absorption?
1)
334
What is normal intracellular calcium concentration? How variable is this?
∼100nM (0.1μM)
| Can increase 10-100 fold during various cellular functions
335
What is normal extracellular calcium concentration? What is plasma calcium concentration?
∼1-3mM
| Plasma: 2.2-2.6mM
336
What is the mechanism of Ca²⁺ absorption?
1) Ca²⁺ carried across apical membrane by IMcal (facilitated diffusion) and ion channels
2) Ca²⁺ binds to Calbindin in cytosol preventing it from acting as an intracellular signal
3) PMCA hydrolyses ATP to pump Ca²⁺ out of cell against concentration gradient (high-affinity)
4) Na⁺Ca²⁺exchanger (low-affinity/high capacity) pumps Ca²⁺ out of cell (needs high concentrations)
337
How does 1,25-dihydroxyD3 increase Ca²⁺ absorption?
Increases levels of calbindin
| Increases rate of extrusion across basolateral membrane by increasing level of Ca²⁺ATPase in the membrane
338
How much iron is ingested per day and how much is absorbed?
Eat: 15-20mg/day
Absorb: 0.5-1.5mg/day
339
What type of iron can be absorbed and which type cannot be absorbed? How does vitamin C aid in absorption?
Cannot absorb Fe³⁺
Only Fe²⁺
Vitamin C reduces Fe³⁺ to Fe²⁺
340
What is the mechanism for iron absorption?
1) Heme binds to HCP-1 which forms a complex and enters the enterocyte cytoplasm
2) Heme oxygenase liberates Fe²⁺ from heme
3) Fe³⁺ in the gut is converted to Fe²⁺ by Dcytb (duodenal cytochrome B) then Fe²⁺ transported via DMT-1 which co-transports H⁺
4) Fe²⁺ carried by proteins to basolateral membrane
5) Ferroportin ion channel transports Fe²⁺ into blood
6) Hephaestin converts Fe²⁺ to Fe³⁺
7) Fe³⁺ binds to apotransferrin and travels in the blood as transferrin
OR
4) Fe²⁺ binds to apoferritin in cytosol to form a ferritin micelle (globular protein complex)
5) Fe²⁺ oxidised to Fe³⁺ (stores up to 4000 ions)
341
How does hepcidin decrease iron absorption?
Suppresses ferroportin and prevents Fe²⁺ transport into blood
342
What is the mechanism for vitamin B₁₂ absorption?
1) Low pH and pepsin release vit B₁₂ (normally bound to proteins)
2) B₁₂ binds to R protein (haptocorrin) released in saliva and from parietal cells
3) R proteins are digested in the duodenum
4) B₁₂ binds to intrinsic factor (made in parietal cells) and forms a complex
5) Travels down to distal ileum and complex gets absorbed into enterocyte by cubulin receptor
6) B₁₂-IF complex broken down by mitochondria
7) B₁₂ binds TCII and forms complex and is transported into the bloodstream
8) B₁₂-TCII travels to the liver and is taken up by TCII receptors
9) Proteolysis breaks down TCII inside the cell and B₁₂ stored in the liver
343
How is vitamin K taken up into cells?
```
Active transport
(most others passive diffusion)
```
344
How do you approach pain?
History
Examination
Investigation
345
What is the nemonic for pain?
```
Site
Onset
Character
Radiation
Associated Symptoms
Timing
Exacerbated/relieving factors
Severity
```
346
What are the 9 regions of the abdomen?
```
Right hypochondrium
Epigastrium
Left hypochondrium
Right lumbar
Umbilical
Left lumbar
Right iliac
Suprapubic
Left iliac
```
347
What are the characteristics of GI pain?
Initially poorly loacted
Onset usually over hours (can be very quick)
Usually more of a dull ache
May have associated GI symptoms
348
Where does foregut pain usually present?
Epigastric region
349
Where does midgut pain generally present?
Umbilical pain
350
Where does hindgut pain usually present?
Suprapubic pain
351
Where does retroperitoneal pain usually present?
Back pain
352
Where does diaphragm pain usually present?
Shoulder tip pain
353
How does peritonitis present?
Sharp, very severe pain. Located initially but becomes more generalised. Worse on movement
Guarding
Rebound tenderness
354
What is guarding?
```
On examination (palpation) of the stomach the muscles tense up involuntarily around the area.
Protective mechanism
```
355
What is rebound tenderness?
Pain on removing hand quickly following an examination
356
Patient presents with gradual onset left flank pain.
Comes and goes
Radiates from flank to groin
Worst pain ever, no relief from pain killers. Which system is it? What is the cause
Renal
| Kidney stones
357
What is colicky pain?
```
A muscular contraction of a hollow tube in an attempt to relieve an obstruction by forcing content out. It may be accompanied by vomiting and sweating
Can occur in:
Ureter
Urethra
Colon
Bile ducts
Pancreatic ducts
```
358
Describe acute pancreatitis
Very variable presentation
Abdo pain localised to the epigastrium and radiating to the back
Nausea and vomiting common
Patient acutely unwell and in shock
May have organ failure (chest/kidney)
May also have evidence of jaundice/cholangitis
POTENTIALLY VERY UNWELL
359
What simple bedside tests can you do for acute pancreatitis?
Blood pressure
Pulse
Urine dipstick
360
What blood tests can you do for acute pancreatitis?
```
Full blood count
Urea and electrolytes
Inflammation markers (CRP, ESR)
Liver function tests
Clotting
Calcium
Glucose
```
361
What complex blood tests would you conduct for acute pancreatitis?
Amylase
Lipase
Triglycerides
362
What imaging would you conduct for acute pancreatitis?
Chest X-ray
Abdominal X-ray
Ultrasound
CT scan
MRCP
363
What invasive tests would you perform for acute pancreatitis?
ERCP
364
What is the most common cause of pancreatitis in the UK?
Gall stones
365
What are the causes of pancreatitis?
```
Gall stones
Ethanol
Trauma
Steroids
Mumps
Autoimmune
Scorpion venom
Hyperlipidaemia/hypercalcaemia
ERCP
Drugs
```
366
What are the systemic complications of pancreatitis?
```
Hypovolaemia
Hypoxia
Hypocalcaemia
Hyperglycaemia
DIC
Multiple organ failure
```
367
What are the localised causes of pancreatitis?
Pancreatic necrosis
Fluid collections (mature into pseudocysts)
Splenic vein thrombosis/pseudoaneurysm
Chronic pancreatitis
368
What cancer arises from squamous cells?
Squamous cell carcinoma
369
What cell type are most GI cancers?
Adenocarcinoma
| from glandular epithelium
370
What type of cancer arises from glandular epithelium?
Adenocarcinoma
371
What type of cancer arises from enterochromaffin cells?
Carcinoid tumours
372
What type of cancer arises from interstitial call of Cajal?
Gastrointestinal stromal tumours
373
What type of cancer of the GI tract arises from smooth muscle?
Leiomyoma / leiomyosarcomas
374
What type of cancer of the GI tract arises from adipose tissue?
Lipomas
375
What types of cancer can present in the oesophagus?
Adenocarcinoma
| Squamous cell carcinoma
376
Describe adenocarcinoma of the oesophagus
From metaplastic columnar epithelium
Lower 1/3 of the oesophagus
Related to acid reflux
More common in developed world
377
Describe squamous cell carcinoma
From normal oesophageal squamous epithelium
Upper 2/3 of the oesophagus
Acetaldehyde pathway
More common in developing world
378
What is the most common type of oesophageal cancer in the UK?
Adenocarcinoma
379
What is the progress from reflux to cancer in the oesophagus?
1) Oesophagitis (inflammation)
2) Barrett's (metaplasia)
3) Dysplasia
4) Carcinoma (neoplasia)
380
What is Barrett's oesophagus?
Metaplasia
| Reflux causes squamous cells to be replaced by columnar cells
381
What is the risk of developing cancer per year if you have Barrett's oesophagus, low grade dysplasia and high grade dysplasia?
Barrett's→0.12%
LGD→0.5%
HGD→5-30%
382
What are the risk factors for bowel cancer?
```
Family history
Spacific inherited conditions (FAP, HNPCC, Lynch syndrome)
Uncontrolled ulcerative colitis
Age
Previous polyps
```
383
What is the progression from normal epithelium in the bowel to carcinoma?
1) Normal epithelium
2) Hyperproliferative epithelium. Abberant cryptic foci
3) Small adenoma
4) Large adenoma
5) Colon carcinoma
384
What stimuli have been found to increase the progression of cells to carcinoma in the bowel?
Aspirin and other NSAIDs
Folate
Calcium
Oestrogen
385
What is the inheritance of colon cancer?
Not simple Mendelian inheritance- not a single gene process
Sequence of genetic errors
- APC, K-ras, p53, 18q
386
What are are the symptoms of bowel cancer?
```
Largely asymptomatic (incidental anaemia)
Change in bowel habit
- Diarrhoea
- Constipation
Blood in stool
Acute intestinal obstruction
```
387
What are the advantages of an abdominal x-ray? What is the specificity and sensitivity?
- Cheap
- Easy
- Quick
Sensitivity for obstruction 77%
Specificity for obstruction 50%
388
What are the advantages and disadvantages of a CT scan?
```
Advantages
- Quick
- Easy
- See large lesions
Disadvantages
- May miss smaller lesions (
```
389
What are the advantages of colonoscopy? What are the risks?
```
Advantages?
- Safe
- Relatively quick
- High sensitivity
- Able to obtain tissue
Disadvantages
- 2 days of iatrogenic diarrhoea
- small risk of perforation (
```
390
What are the advantages and disadvantages of CT virtual colonoscopy?
```
Advantages
- Quick
- Easy
- Reduced bowel prep more tolerable
- As good as colonoscopy for lesions >6mm
Disadvantages
- Unable to obtain tissue
- Unable to remove lesions
```
391
What is Virchow's triad for pancreatic cancer?
Pain - 70%
Anorexia - 10%
Weight loss - 10%
392
What are the early symptoms of pancreatic cancer?
Abdominal pain
Depression
Glucose intolerance
393
What are the late symptoms of pancreatic cancer?
Weight loss
Jaundice
Ascites
Obstructed gall bladder
394
What is the outcome of pancreatic cancer?
- Only 20% are suitable for a resection
- Surgery is curative in 20-25% of cases
1 year survival 18%
5 year survival 2%
395
What are the risk factors for pancreatic cancer?
```
Smoking
Drinking
Obesity
Family history
- Especially rare conditions such as Multi Endocrine Neoplasia
```
396
What type of cancer is bowel cancer?
Adenocarcinoma
397
What is the microbiota?
The qualitative and quantitative information about the different microbes present in a system- what is there and how abundent
398
What is the microbiome?
The functions that the microbiota have, e.g. bile metabolism- their gene catalogue
399
What is metagenomics?
Either "gain-of-function" or DNA based approach to create gene catalogues, used to define the microbiome
400
What is metataxonomics?
Creation of 16S rRNA gene inventories, used to define the microbiota.
401
What is metabonomics?
A cataglogue of the metabolites in a sample (metabolomics in a tissue or isolate)
402
What factors change your microbiome?
Diet (vegan/carnivore)
Pregnancy
Antibiotics
Surgery
403
How many species are there in the large intestine?
160
404
What gene do all organisms have? Why?
16S rRNA gene
| House keeping gene requires for protein synthesis
405
How much of stool is microbial biomass?
50-55%
406
What is the gut microbiota comprised of?
Viruses: 1200 viral genotypes
Eukaryotes
Bacteria: >1000 bacterial species but 160 per person and possibly >7000 strains
407
What are the functions of the gut microbiota?
```
Defence- bacteria antagonism
Priming of mucosal immunity
Peristalsis
Metabolism of dietary carcinogens
Synthesis of B and K vitamins
Epithelial nutrients (e.g. SCFAs- butyrate)
Conversion of prodrugs
Utilisation of indigestible (CH2O)n
```
408
What are the disadvantages of microbiota?
Procarcinogens → carcinogens
Overgrowth syndromes
Oppotunism - Translocation
Essential ingredient for IBD
Utilisation of indigestible (CH₂O)n- obesity
Role of insulin resistance and non-alcoholic fatty liver disease
409
What is amensalism? (gut microbiome)
One organism grows and in doing so inadvertently damages another, but it is not evolved to do so - collateral damage
410
What is the function of bile?
```
Cholesterol homeostasis
Dietary lipid/vitamin absorption
Removal of xenobiotics / drugs / endogenous waste products e.g.
- cholesterol metabolites
- adenocortical
- other steroid hormones
```
411
What are the fat soluble vitamins?
ADEK
412
What is the composition of bile?
```
Water 97%
Bile salts 0.7%
Inorganic salts 0.7%
Bile pigments (bilirubin, bilivirden) 0.2%
Fatty acids 0.15%
Lecithin 0.1%
Fat 0.1%
Cholesterol 0.06%
```
413
How much bile is produced per day?
500ml produced / secreted daily
414
Where is bile secreted?
60% hepatocytes
415
At what point does bile enter the duodenum?
Duodenal papilla
416
What is the role of the biliary tree?
40% bile secreted by cholagiocytes
Alters pH, fluidity and modifies bile as it flows through
H₂O drawn into bile via osmosis through paracellular junctions
Luminal glucose and some organic acids reabsorbed
HCO₃⁻ and Cl⁻ actively secreted inot bile by CFTR mechanism
Cholangiocytes contribute IgA by exocytosis
417
What cells line the bile ducts?
Cholangiocytes
418
Bile flow is closely related to what?
Concentration of bile acids and salts in the blood
419
What performs biliary excretion of bile salts and toxins?
Transporters on apical surface of hepatocytes and cholangiocytes
420
What causes cholestasis?
Dysfunction of transporters
421
What are the main bile transporters?
1) Bile salt excretory pump (BSEP)
2) MDR related proteins (MRP1 and MRP3)
3) Products of the familial intrahepatic cholestasis gene (FIC1) and multidrug resistance genes (MDR1 and MDR3)
422
What is the role of BSEP in bile flow?
Active transport of bile acids across hepatocyte canalicular membranes into bile, and secretion of bile acids is a major determinant of bile flow
423
What is the role of MDR1 in bile flow?
Mediates canalicular excretion of xenobiotics, cytotoxins
424
What is the role os MDR3 in bile flow?
Encodes a phospholipid transporter protein that translocates phosphatidylcholine from inner to outer leaflet of canalicular membrane
425
How many bile acids are there in humans?
Four
426
What are bile acids synthesised from?
Cholesterol
427
What are the two primary bile acids?
Cholic acid
| Chenodeoxycholic acid
428
What are the two secondary bile acids and what are they produced from?
```
Deoxycholic acid (from cholic acid)
Lithocholic acid (from chenodeoxycholic acid)
```
429
What convert primary bile acids to secondary bile acids?
Action of colonic bacteria
430
What is the function of bile salts?
Reduce surface tension of fats
| Emulsify fat preparatory to its digestion / absorption
431
How does bile from each lobe of the liver drain into the gall bladder?
Right lobe drains into right hepatic duct
Left lobe drains into left hepatic duct
Both ducts drain to the common hepatic duct
This drains into the cystic duct (into the gall bladder)
432
How does cholecystokinin stimulate the release of bile?
Stimulates the sphincter of Oddi to open
| Stimulated the gall bladder to contract
433
What proportion of bile salts are absorbed in the terminal ileum? What happens to the proportion that isn't absorbed?
95%
5% is converted to secondary bile acids in the colon
- deoxycholate absorbed
- lithocholate 99% excreted in stool
434
How does terminal ileal disease affect bile salts?
Decreased bile salt reabsorption and increased stool fat concentration
This is because the enterohepatic circulation is interrupted and the liver can't increase the rate of bile salt production enough to make it up
435
How many times does the 3g bile salt pool recycle in the enterohepatic circulation per meal and per day?
Twice per meal
| 6-8 times per day
436
What happens if bile is stopped from entering the gut?
437
What are the functions of the gall bladder?
1) Stores bile (50ml)
2) Acidifies bile
3) Concentrates bile
By H₂O diffusion following a net absorption of Na⁺, Cl⁻, Ca²⁺ and HCO₃⁻
- Can reduce the volume of stored bile by 80-90%
438
What are the effects of cholecystectomy?
Periodic discharge of bile from gall bladder aids digestion but is not essential
Normal health and nutrition exist with continuous slow bile discharge into duodenum
Avoid foods with high fat content
439
What is bilirubin? Where does it originate in the body?
A H₂O insoluble yellow pigment
75% from Hb breakdown
22% from catabolism of other haem proteins
3% from ineffective bone marrow erythropoiesis
440
What is the mechanism of bilirubin uptake into bile?
1) Binds to albumin and dissociates in the liver
2) Free bilirubin enters hepatocytes and binds to cytoplasmic proteins
3) Conjugated to glucoronic acid (UDPGT from smooth ER)
4) Produces diglucoronide-bilirubin which is more soluble than free bilirubin
5) Transported across concentration gradient into bile canaliculi
441
What is total bilirubin in the body comprised of?
Free bilirubin (unconjugated)
AND
Conjugated bilirubin
442
What is urobilinogen? How is it formed? What is the fate of urobilinogen?
H₂O-soluble, colourless derivative of bilirubin formed in gut by bacterial action on bilirubin.
Half of the produced urobilinogen is reabsorbed and taken up via the portal vein to the liver, enters the circulation and is excreted by the kidney
443
What type of bilirubin is the gut permeable to?
Unconjugated bilirubin and urobilinogens
444
What type of bilirubin is present in the urine and the faeces?
Urine: Urobilinogens
Faeces: Stercobilinogen
445
Explain the bilirubin metabolism and excretion pathway
1) Erythrocyte breakdown in spleen releases unconjugated bilirubin
2) In the liver → conjugated bilirubin in bile
3) Secreted into duodenum
4) Small amount of reduced bilirubin is reabsorbed into portal vein → liver → systemic blood supply → kidneys (secreted as urobilonogen)
5) Bilirubin reduced by gut bacteria to stercobilinogen
6) Oxidised to stercobilin in faeces (brown colour)
446
What is jaundice?
Excess bilirubin in blood
| >34-50μM/L
447
What is a normal bilirubin level?
448
What are the three different types of jaundice?
Pre-hepatic
Hepatic
Post-hepatic
449
What is pre-hepatic jaundice?
```
Usually in the spleen
Increased quantity of bilirubin
- Haemolysis
- Massive transfusion
- Haematoma resorption
- Ineffective erythropoiesis
Presents with normal liver function and low Hb
```
450
What is hepatic jaundice?
```
Defective:
- uptake
- conjugation
- Bilirubin excretion
Liver failure
- Acute / fulminant
- Acute on chronic
- Viral hepatitis, alcohol, autoimmune disease etc
Intrahepatic cholestasis: sepsis, TPN, drugs
```
451
What is post-hepatic jaundice?
Defective transport of bilirubin by biliary duct system e.g. common bile duct stones, HepPancBil malignancy, local LNpathy
Sepsis (cholangitis)
452
In what types of jaundice will there be more unconjugated and conjugated bilirubin?
Unconjugated: Hepatic jaundice
Conjugated: post hepatic
453
What is Gilbert's syndrome?
Commonest hereditary cause of increased bilirubin
Up to 5% of the population (autosomal recessive inheritance)
Elevated unconjugated unconjugated bilirubin in bloodstream
Cause: 70-80% reduction in glucuronidation activity of the enzyme UDPGT-1A1
No serious consequences
Mild jaundice may appear under:
- exertion, stress, fasting, infections
454
What is acute liver failure?
When hepatocyte death > hepatocyte regeneration
455
What is the most common cause of acute liver failure?
Paracetamol overdose
456
What are the causes of acute liver failure?
```
Diseases of pregnancy
Idiosyncratic drug reactions
Vascular Diseases
Metabolic causes
- Wilson's disease
- Reye's syndrome
```
457
At what does is paracetamol toxicity possible?
>10g
| Severe toxitiy certain >25g
458
What are the consequences of liver failure?
```
Encephalopathy and cerebral oedema
Hypoglycaemia
Coagulopathy and bleeding
Increased susceptibility to infection
Circulatory collapse, renal failure
```
459
What are the symptoms of acute liver failure?
Malaise, nausea, lethargy
| Jaundice
460
What is the function of the gut microbiota?
Immune function
Metabolic function
Physiological function
Trophic function
461
What is oral candidiasis? Who does it infect? How is it treated?
Candida albicans (yeast/fungal infection)
Carried in 50%
In immunocompromised states e.g. HIV, chemotherapy or corticosteroids
Treat with oral anti-fungals e.g. nystatin or IV antifungals is immunocompromised
462
What is helicobacter pylori? What does it cause? How is it treated?
Gram negative microaerophilic rod
Causes excess acid production
Gastritis/ gastric or duodenal ulcers / gastric carcinoma
80% of infected are asymptomatic
Investigation: blood antibody, stool antigen, urea breath test, biopsy ureases test
Treatment: 1 week eradication therapy with proton pump inhibitor and clarithromycin / amoxicillun
463
What are the main causes of travellers diarrhoes?
```
E. coli
Shigella
Salmonella
Cholera
Rotavirus
Norovirus
Giardia
```
464
What is norovirus? How is it transmitted?
Acute gastroenteritis
465
What is the treatment for C. difficile?
```
Isolate
Stop current antibiotics
Metronidazole
Vancomycin
Faecal microbiota transplantation
```
466
What is MALT?
Mucosa associated lymphoid tissue
467
What is GALT?
Gut associated lymphoid tissue
468
What is the epithelial barrier to prevent infection in the gut?
```
Mucous layer
- Goblet cells
Epithelial monolayer
- Tight junctions
- Antimicrobial peptides
- Transports IgA
Paneth cells
- Bases of crypts
- Defensins
- Lysozyme
```
469
What, if any, immunological tissue is in the oral cavity?
Rich in immunological tissue (MALT)
470
What are the different types of GALT?
```
Not Organised
- Intra-epithelial lymphocytes
- Lamina propria lymphocytes
Organised
- Cryptopatches
- Peyer's patches
- Isolated lymphoid follicles
- Mesenteric lymph nodes
```
471
What is the function of GALT?
```
Generates lymphoid cells and antibodies
- IgA secretory and interstitial
- IgG
IgM
- Cell mediated immunity (adaptive and innate
```
472
What are Peyer's patched? Where are they found?
Small intesting- mainly distal ileum
Organised collection of naive T and B-cells
Covered by follicle associated epithelium (FAE)
- No goblet cells
- No secretory IgA
- Lack microvilli
- Infiltrated by T-cells, B-cells, macrophages, dendritic cells
Antigen uptake via (microfold) M-cells within FAE
473
What is the function of Peyer's patches?
Antigen sampling by M-cells
Transport to antigen-presenting cells in sub-epithelial dome
- DCs take up antige and process
- Present to naive B or T-cells in Peyer's patch or transport antigen to lymph nodes
- Results in development of gut homing markers
Transfer to mesenteric lymph node to proliferate
474
What is the B-cell adaptive response in Peyer's patches?
Mature naive B-cells expressing IgM in PPs
Upon antigen presentation class switch to IgA
Influences by presence of T cells and epithelium via cytokines
Further maturation to become IgA secreting plasma cells
Populate lamina propria
475
What does IgA secreting cell number indicate?
Bacterial load
| Up to 90% of gut B-cells secrete IgA
476
What is the role of IgA in the gut?
Dimeria structure at mucosal surfaces
Transported by epitheial cells into lumen by transcytosis
Binds luminal antigen
Prevents invasion
Prevents adherence
Does not activate complement or cytotoxic lymphocytes
477
What are intra-epithelial lymphocytes?
Make up 1/5th of the intestinal epithelium
Conventional T-cells (also lamina propria)
- Migrated from other tissues
Unconventional T cells (innate)
- Resident
- Express unusual combinations of CD4, CD8 or γδ T cell receptor
Other innate immune cells
- Resident NK cells (e.g. NKp44+ NK cells)
478
What is required for a T-cell adaptive response?
1) Presentation of antigen on MHC
2) Co-stimulatory signals on DC
3) Secretion of cytokines by DC
479
What are the different types of T-cell and their function?
Th1- Cellular immunology, autoimmunity
Th2- Humoral immunity, atopy, asthma, allergy
iTreg- Immunoregulatory function
Th17- Inflammation, autoimmunity
480
What is immune tolerance? What are the mechanisms?
Suppression of immune responses towards antigens
1) Deletion of responding lymphocytes
2) Anergy
3) Treg cells
481
What causes inflammatory bowel disease?
```
Genetic background
Immune system
Environmental factor
- smoking
- stress
- diet
- vitamin D
```
482
What is the enteric nervous system?
In the wall of the GI tract
Rich plexus of ganglia (nerve cells and glial cells) interconnected by tracts of fine unmyelinated nerve fibres
Can function independently of central control
483
What does the enteric nervous system regulate?
```
Motility
Blood flow
Water and electrolyte transport
Secretion
Absorption
```
484
What are the types of neuron in the enteric nervous system?
Sensory: respond to mechanical, thermal, osmotic and chemical stimuli
Moto: axons terminate on smooth muscle cells of the circular or longitudinal layers, secretory cells of the gastrointestinal tract, or gastrointestinal blood vessels
Interneurons: neurones between neurones integrate the sensory input and effector output
485
What is the myenteric plexus?
Located between the circular and longitudinal smooth muscle layers. Controls activity of muscularis externa. CONTROLS GUT MOTOR FUNCTION
486
What is the submuscosal plexus?
Sensing environment within lumen. Blood flow, epithelial and endocrine cell function
487
What nerve carries innervation to the fore and midgut?
Thoracic splanchnic nerves
488
What nerve carries innervation to the hindgut?
Lumbar splanchnic nerve
489
What is the main neurotransmitter in the sympathetic nervous system
Noradrenaline
490
Where so preganglionic parasympathetic neurones synpase with the enteric nervous system?
Close to the gut wall or directly with enteric plexi
491
How much of the GI tract is innervated by the vagus nerve? What nerve innervates the rest of the GI tract?
Most of the GI tract down to the level of the transverse colon
Pelvic nerve innervates remainder of the colon, rectum and anus
492
What is the main neurotransmitter for the parasympathetic nervous system?
Acetyl choline
493
What cells are modulated by the myenteric plexus and the submucosal plexus?
Smooth muscle
Endocrine cells
Secretory cells
Blood vessels
494
What is the afferent extrinsic innervation of the GI tract used for?
Pain, nausea, fullness
495
What are the functions of the GI endocrine system?
Can act as paracrine or neurocrine factors
496
What is the structure of enteroendocrine cells?
```
Cone shaped (cell body near basal end of cell- near the blood supply)
Projection to the lumen to detect and regulate the GI system
```
497
What is the function of the GI endocrine system?
1) Regulate the mechanical processes of digestion (e.g. smooth muscle, sphincters, gall bladder)
2) Regulate the chemical and enzymatic processes of digestion
3) Control of post-absorptive processes of digestive food and CNS feedback regulating intake
4) Effects on the growth and development of the GI tract (e.g. GLP-2)
498
What are the paracrine actions of the GI tract?
1) Histamine released from stomach wall cells is a key physiological stimulus to HCl secretion by gastric parietal cells
2) Somatostatin from the stomach can inhibit acid secretion by paracrine mechanisms
499
What is gastrin? Where is it secreted?
Synthesised in gastric antrum and upper small intestine
Release stimulated by:
Amino acids and peptide in the lumen of the stomach
Gastric distension
Vagus nerve directly
Gastrin stimulates gastric acid secretion
Release inhibited when pH of stomach falls below pH 3
500
What is somatostatin? Where is it released?
Synthesised in endocrine D cells of the gastric and duodenal mucosa, pancreas (hypothalamus)
Is a universal inhibitor
Released in response to a mixed meal
Inhibits
Gastric secretion, motility, intestinal and pancreatic secretions, release of gut hormones, intestinal nutrient and electrolyte transport, growth and proliferation
Analogues used to treat neuroendocrine tumour
501
What is secretin? Where is it released?
Secreted by the S cells of the upper duodenum and jejunum
| Major stimulus is the presence of acid in the duodenum (pH
502
What is cholecystokinin? Where is it released?
Secreted by cells most densely located in the small intestine
Release stimulated by fat and peptides in the upper small intestine
Independent of the vagus
- stimulates pancreatic enzyme release
- delays gastric emptying
- stimulates gallbladder contraction
decreases food intake and meal size
503
What is glucose-dependent insulinotropic peptide? Where is it released?
Secreted by mucosal K cells (predominant in the duodenum and jejunum)
GIP released following ingestion of a mixed meal
Stimulates insulin secretion
GIP receptor antagonists reduce postprandial insulin release
504
What is peptide YY (PYY)?
Cells found throughout the mucosa of the terminal ileum, colon and rectum
Released from L cells post prandially (particularly protein)
PYY reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion
Inhibitor of intestinal fluid and electrolyte secretion
PYY3-36 inhibits food intake
505
When is thirst perceived?
1) Body fluid osmolality increases- MAIN
2) Blood volume is reduced
3) Blood pressure is reduced
506
What is the function of vasopressin?
Acts on the kidneys to regulate the volume and osmolality of urine
When plasma ADH is low a large volume of urine is excreted (water diuresis)
When plasma ADH is high a small volume of urine is excreted (anti diuresis)
507
How do osmoreceptors cause ADH release?
Found in the hypothalamus- OVLT and SFO
Sense changes in body fluid osmolality
Cells shrink or swell in response (expand when plasma is more dilute and vice versa)
Sends signals to the ADH producing cells in the hypothalamus to alter AHD release
Same regions regulate thirst
508
How is the sensation of thirst regulated?
Receptors in mouth, pharynx, oesophagus decrease thirst before it has been absorbed
Thirst only completely satisfied once plasma osmolality has been corrected
509
How is angiotensin II related to thirst?
Stimulates thirst
510
How is the arcuate nucleus involved in appetite regulation?
Incomplete blood brain barrier allows access to peripheral hormones
Integrates peripheral and central feeding signals
Two neuronal populations:
Stimulatory: NPY/Agrp neuron
Inhibitory: POMC neuron
Cell bodies in the arcuate nucleus and extend to paraventricular nucleus
511
How do POMC and Agrp affect food intake?
POMC (arcuate nucleus)→ α-MSH which stimulates MC4R in paraventricular nucleus which decreases food intake
Agrp (arcuate nucleus) inhibits MC4R
512
What mutations have been associated with morbid obesity?
POMC deficiency and MC4-R mutations
513
What is the adipostat mechanism?
Body's way of working out how much fat you have
Circulating hormone produced by fat
Hypothalamus senses the concentration of hormone
Hypothalamus then alters neuropeptides to increase or decrease food intake
514
What is leptin?
Made by adipocytes in white adipose tissue
Circulates in plasma
Acts upon the hypothalamus regulating appetite and thermogenesis (expenditure)
Low when low body fat
High when high body fat
Hormone that decreases food intake and increases thermogenesis
515
How can leptin lead to obesity?
Leptin circulates in plasma in concentrations proportional to fat mass
Fat humans have high leptin
Obesity due to leptin resistance-hormone is present but doesn't signal effectively
No leptin causes you to be starvingly hungry all the time
516
What does PYY do?
Inhibits NPY release
Stimulates POMC neurons
Decreases appetite
517
What is ghrelin? What does it do?
```
Drives hunger before a meal
Stimulates NPY/Agrp neurons
Inhibits POMC neurons
Increases appetite
Increases food intake
```
518
What comorbidities are associated with obesity?
```
Depression
Sleep apnoea
Bowel cancer
Osteoarthritis
Gout
Stroke
Myocardial infarction
Hypertension
Diabetes
Peripheral vascular disease
Liver disease
Pancreatitis
Infertility
Arthritis
Gall stones
```
519
What is leptin?
Afferent hormone released from adipose tissue acts on hypothalamus to:
- decreases food intake
- increases thermogenesis
- affects fat and glucose metabolism
520
What is the biochemistry of ethanol?
Methyl group + methylene group (=ethyl group) + hydroxy group
Insoluble in fats and oils
521
How is ethanol metabolised?
1) Ethanol (alcohol dehydrogenase) → Acetaldehyde (+NADH) (aldehyde dehydrogenase) → acetate (+NADH)
2) Ethanol → Catalase → Acetaldehyde
3) Ethanol → CYP2E1 → Acetaldehyde
522
What test is used to stage alcohol drinking?
AUDIT
Alcohol-use disorders identification test
Can detect 92% of genuine hazardous and harmful drinking
523
How does ethanol damage cells?
Direct
| Indirect (as a result of metabolites)
524
How many deaths from liver disease are due to alcohol consumption?
∼75%
525
How does ethanol cause liver damage?
Metabolism pathways produce:
1) Alcohol dehydrogenase
- ↓ fatty acid oxidation
- ↑ Glyceraldehyde reduction
- ↑ oxygen consumption
2) CYP2E1
- Protein adduct formation
- Free radical generation
- Induction of xenobiotic metabolism
526
What is the progression of chronic alcohol misuse?
1) 90-95% Steatosis
2) 10-20% Fibrosis
3) 8-20% Cirrhosis
4) 3-10% Hepatocellular carcinoma
527
What is steatosis?
Fat droplets deposited in the liver
Occurs in 50-90% of heavy drinkers
Leads to steatohepatitis and abnormal LFTS
Reversible is alcohol consumption is reduced
528
What is hepatic fibrosis?
Chronic inflammation leads to transformation of hepatic stellate cells into fibroblasts which begin to lay down collagen fibres which condense into fibrous bands
529
What makes people more susceptible to cirrhosis?
```
Genetic
Females
Smoking
Viral hepatitis
HIV
Obesity and insulin resistance
```
530
What is cirrhosis?
Irreversible scarring of liver with fibrous bands and regenerative nodules
Impaired function. Development of portal hypertension
Morbidity common, associated with jaundice, ascites, bleeding, cachexia, infections and encephalopathy
3-5% per annum risk of developing liver cancer
Death in most within 10 years
531
What are the different types of cirrhosis?
Compensated (asymptomatic) vs. Decompensated (symptomatic)
532
What are the symptoms of cirrhosis?
```
Jaundice
Bleeding varices
Ascites (fluid retention)
Encephalopathy (cognitive issues)
- memory loss
- seizures
- loss of consciousness
```
533
What is Child-Pugh?
Way of classifying liver disease
| A/B/C
534
Describe chronic pancreatitis
```
Up to 45% due to alcohol
Exocrine insufficiency
- Steatorrhoea
- vitamin deficiencies
- hypocalcaemia
Endocrine insufficiency
- diabetes
Chronic pain
Weight loss
```
535
What effect does alcohol consumption have on the cardiovascular system?
Hypertension
| Alcoholic cardiomyopathy
536
How does alcohol affect the risk of stroke?
High alcohol intake is associated with risk of stroke
| The effect is dose dependent
537
What are the neurological effects of alcohol?
```
Wernicke's encephalopathy
Korsakoff's psychosis
Optic toxicity
Autonomic dysfunction
Peripheral neuropathy
```
538
Describe foetal alcohol syndrome?
Specific pattern of facial features
Pre- and/or postnatal growth deficiency
Evidence of central nervous system dysfunction
539
What is the alcohol-harm paradox?
Deprived populations that apparently consume the same or less alcohol than less deprived populations suffer greater levels of harm
540
What is one unit of alcohol?
8g of alcohol
541
What are the safe alcohol consumption guidelines?
14 units per week, spread evenly over 3 days or more (not consecutive)
542
What are the bands of BMI?
```
>20 Underweight
20-25 Healthy
26-30 Overweight
31-40 Obese
>40 Morbidly obese
```
543
How is undernourishment measured?
Complicated by fluid balance- body weight not necessarily the best indicator
Arm circumference
544
How is nourishment of children measured?
Growth charts- fine as long as they stay in the same percentile
If they cut percentiles- concern
545
What is body weight a reflection of?
Total cell mass
| NOT nourishment
546
In some cases of malnutrition body weight is not reflective of nutritional status. Why?
Oedema confounds body weight
547
What are dietary reference values based on?
The requirements OF A POPULATION
548
How is the reference nutrient intake derived?
Estimate average intake (mean requirement) + 2.5 standard deviations
549
In which case is the estimated average intake (not EAI+2.5SD) used as a reference value?
For energy because of the problems with obesity
550
What is the role of vitamin C? What occurs if there is a deficiency?
```
Ascorbic acid
Antioxidant
- Converts Fe³⁺ to Fe²⁺
Important in the formation of collagen
Deficiency: Scurvy
15-50+: 40mg/day
varies in different countries
```
551
What is BMR?
Basal metabolic rate
| Energy expenditure required for cellular and organ functions
552
What is RNI?
Level at which most nutritional recommendation are set
| EAR + 2.5SD
553
What three components make up your energy expenditure?
BMR
Adaptive thermogenesis
Exercise
554
Why does energy requirements decrease as you age?
Because you lose muscle
555
What are the fates of acetyl CoA?
```
Pyruvate
Amino acid
Fatty acid
TCA
Ketone bodies
```
556
What are the different energy stores in the body?
```
Glycogen
- stored in the liver and muscle
Adipose tissue
- Major store
Muscle
- Prolonged starvation
```
557
How does alcohol affect the macronutrient balance?
Alcohol will be used for energy first and the rest of the energy intake will be shifted into storage
558
What is the macronutrient balance?
Intake - Expenditure = Stores
559
How does body composition change between a foetus and a full term baby?
Body fat massively increases- need it as a buffer as no longer have a constant supply of energy
Water decreases
560
What are the complications relative to loss of lean body mass?
```
10% loss
- Impaired immunity, increased infection
20% loss
- Decreased healing, weakness, infection
30% loss
- Too weak to sit, pressure sores, pneumonia, no healing
40% loss
Death, usually from pneumonia
```
561
What effect does severe malnutrition have on children?
Delays in chemical maturation
| Can effect IQ
562
What are the causes of undernutrition in the developed countries?
```
Age
Change in social circumstances
- Isolation
- Death of a partner
- Poor housing
Illness
10% of free living elderly people are undernourished to a degree where their function is effected
```
563
What are the signs of undernutrition?
```
Weight loss
Loss of subcutaneous fat
Muscle wasting
Peripheral oedema
Glossitis (cracking edges of mouth)
Hair loss
Chronic infections
Poor wound healing, chronic wounds, pressure sores
Listless, apathetic
Recurrent pulmonary infections
```
564
What methods does the body have to reduce resting metabolic rate?
PASSIVE
Response to negative energy balance
- ↓ Insulin
- ↓ T4→T3= ↓ T3
- Glucagon
- GH
Causes substrate mobilisation of free fatty acids and amino acids
→ Weight loss and change in body composition
ACTIVE
Response to reduced energy flux
- ↓ SNS activity and catecholamines
Causes ↓ metabolic flux and ↓energy expenditure
→ Decrease in metabolic activity of the FFM
565
What are two undernourishment conditions?
Marasmus
| Kwashiorkor
566
What is marasmus?
```
General energy deficit
Growth failure
No oedema
Uncommon to have mental changes
Good appetite
```
567
What is kwashiorkor?
```
Relative protein deficit
Growth failure
Oedema
Mental changes
Poor appetite
```
568
What happens to energy expenditure in marasmus?
It decreases
569
What is thiamine?
Vitamin B₁
Critical for release and utilisation of energy from food and nerve function
Present in free form and TMP, TTP, TPP
570
What condition is associated with thiamine deficiency? Describe the condition
Beriberi
Nervous system ailment
Thiamine is involved in breakdown of energy molecules such as glucose and is found on the membranes of neurons
Symptoms include severe lethargy, fatigue and complications affecting the cardiovascular, nervous, muscular and GI systems
571
What is Niacin?
Vitamin B₃ (synthesised from troptophan)
Nicotinamide is a derivative of niacin used by the body to form coenzymes NAD and NADP
200 enzymes require the niacin coenzymes
572
What is Pellagra?
Deficiency of niacin
573
Why are specific nutrient deficiencies rare?
Most nutrient deficiencies are related to general poor energy intake
574
What is the ideal consumption ratio of carbohydrate, protein and fat?
Carbohydrate: 50%
Fat: 33%
Protein: 17%
575
Why does weight loss slow down as an individual diets?
As you lose weight you resting energy expenditure decreases so it becomes harder to lose weight
576
How are energy stores and risks of excess weight assessed?
1) Weight and height
| 2) Regional adiposity/ energy partitioning (higer risk of CVS if on abdoment)
577
What is used to define a patient as obese?
1) Weight
2) Presence of co-morbidities
3) BMI kg/height²
25-30: overweight
>30: obese
(varies between ethnicities)
4) Waist to hip ratio
Indicates high risk of the metabolic syndrome
578
Who is at risk of the metabolic syndrome?
```
1) Waist circumference
Men >102
Women >88
2) Fasting glucose
>6.0mmol/L
3) HDL
Men135/80
5) Microalbumin
Insulin resistance
```
579
How does waist circumference influence CHD risk?
```
Increased risk
Men >94
Women >80
Major risk
Men >102
Women >88
```
580
What are the causes of obesity?
```
Energy intake
Energy usage
Genes
Brain
Endocrinology
Behaviour
Culture
```
581
How does energy intake contribute to obesity?
Increase in fast food intake
Decreased carbohydrate content
Increased fat content
Body can't autoregulate fat as easily as protein
Satiety not as present after fat consumption compared to protein and carb
582
How does energy usage contribute to obesity?
Big reduction in energy expenditure over recent years
| Difficult to quantify
583
How do genes contribute to obesity?
Most obesity is not monogenic
The amount and site of weight gain is in part genetic.
Genetic predisposition to obesity
FTO gene linked to obesity
584
What hormones are involved in energy homeostasis?
1) Leptin
- Released from white adipose tissue
- Regulates thermogenesis and satiety
2) Insulin
- Regulates thermogenesis and satiety
3) Ghrelin
- Stimulates hunger
4) PYY
- Released after eating a big meal
585
How do behaviour and culture contribute to obesity?
Governement
586
How is obesity managed?
1) Lifestyle diet and exercise
2) Pharmacological
3) Bariatric surgery
587
What are the benefits to a 100kg patient losing 10kg (10% of body mass)
```
Psychological benefit
PCOS (fertility)
Oesophagitis improves
CHD risk ↓
Osteoarthritis improves
Liver function improves
Pregnancy ↑
Diabetes improves
Mortality 20% ↓
LDL 15% ↓
HDL 8% ↑
```
588
What is victoza? How does it work?
Treat obesity in patients with diabetes
Works on hormone GLP-1 (glucagon-like peptide-1)
Causes patients to become more full
589
What is Saxenda? How does it work?
The same as Victoza- works on GLP-1 to cause patients to become more full, but licensed for patients with obesity (NOT + diabetes) and at a higher dose
5% weight loss
590
What is belviq? How does it work?
Lorcaserin
Seratonin agonist- works at the level of the hypothalamus
Suppresses appetite
5% weight loss
591
What is Qsymia? How does it work?
Made up of phenelemine and topiramate
Phenelemine is an appetite suppressant
Topiramate is usually given for pain or epilepsy
7-8% weight loss
592
What is Contrave? How does it work?
Made up of Naltrexone and Bupropion
Works in the brain to suppress appetite
5% weight loss
593
What are the problems with obesity medication?
Affects the heart
| Previous medication has increased depression and hypertension
594
What are the possible bariatric surgery procedures for obesity?
Adjustable band
Sleeve gastrectomy
Gastric bypass
595
What is the best option for bariatric surgery? (in terms of mean weight change)
Gastric bypass
596
How does bariatric surgery affect mortality?
Mortality is reduced following bariatric surgery
597
What are the health benefits of bariatric surgery?
```
Improvement of T2DM
Improvement of hypertension
Improved lipid profile
Overall reduction in cardiac risk
Resolution of obstructive sleep apnoea
Resolution of PCOS and improved fertility
Reduced cancer related deaths
Regression of non-alcoholic fatty liver disease
Reduced mortality
```
598
What are the current criteria for bariatric surgery?
BMI >40 with no comorbidities
BMI >35 with comorbidities
BMI 30/34.9 with a short duration of type 2 diabetes
