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Gastrointestinal Flashcards

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1
Q

Name the 5 digestive functions of the stomach:

A

-Store and mix food
-Dissolve and continue digestion
-Regulate emptying into the duodenum
-Secrete proteases
-Secrete intrinsic factor

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2
Q

Name 4 other functions of the stomach:

A

-Kill microbes
-Lubrication
-Activate proteases
-Mucosal protection

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3
Q

What are the key cell types in the stomach?

A

-Mucous cells
-Parietal cells - mainly in fundus
-Chief cells - protease production
-Enteroendocrine cells - hormone production

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4
Q

What is gastric acid secretion?

A

-Hydrochloric acid
-Approx 2 litres/day
-[H+] > 150mM
-Secreted by parietal cells

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5
Q

What is gastric acid secretion dependant on?

A

-Energy dependant as it is active transport (ATP required)
-Neurohormonal regulation

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6
Q

Explain the process of gastric acid secretion:

A

-H+/K+ ATPase transporter protein in parietal cell membrane
-Transports 1 H+ out of the cell into the stomach lumen and 1 K+ into the cell
-Active transport of the hydrogen, passive movement of potassium ions
-K+ transported out of cell into stomach lumen through transport protein
-Cl- transported out of cell into stomach lumen via transporter protein

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7
Q

Explain the process of gastric acid secretion:

A

-H+/K+ ATPase transporter protein in parietal cell membrane
-Transports 1 H+ out of the cell into the stomach lumen and 1 K+ into the cell -> requires energy from ATP hydrolysis
-Active transport of the hydrogen, passive movement of potassium ions
-K+ transported out of cell into stomach lumen through transport protein
-Cl- transported out of cell into stomach lumen via transporter protein

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8
Q

Where do H+ come from in parietal cells to be transported into the stomach lumen?

A

Breakdown of H2O into H+ and OH-

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9
Q

Where do Cl- come from in parietal cells?

A

-Transported from the blood into the parietal cells through a transporter protein
-HCO3- is transported out of the cell into the blood via the same transporter

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10
Q

How is water reformed in parietal cells?

A

-CO2 + H2O -> H2CO3
-Via carbonic anhydrase enzyme
-H2O -> H2CO3 -> HCO3- + H+
-H+ + OH- -> H2O

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11
Q

Label this diagram:
What does it show?

A

Gastric acid secretion

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12
Q

What 3 things turn on gastric acid secretion during cephalic phase?

A

-Parasympathetic nervous system (vagus)
-Sight, smell, taste of food and chewing
-Acetylcholine (ACh) release

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13
Q

What is the effect of ACh on gastric acid secretion and how?

A

-Acts directly on parietal cells
-Triggers release of gastrin and histamine
-Net effect = increased gastric acid production

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14
Q

What 4 things turn on gastric acid secretion during gastric phase?

A

-Gastric acid distension
-Presence of peptides and amino acids
-Gastrin release

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15
Q

How does gastrin affect gastric acid secretion?

A

-Acts directly on parietal cells
-Gastrin triggers release of histamine
-Histamine acts directly on parietal cells
-Net effect = increased gastric acid production

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16
Q

Why is histamine important in gastric acid secretion?

A

-Acts directly
-Mediates effects of gastrin and acetylcholine

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17
Q

By what mechanism does protein in the stomach affect gastric acid secretion?

A

-Direct stimulus for gastrin release
-Proteins in lumen act as a buffer - mopping up H+ ions, causing pH to rise
-Causes decreased secretion of somatostatin
-More parietal cell activity - lack of inhibition

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18
Q

How does pH affect the turning off of gastric acid secretion during gastric phase?

A

-Low luminal pH (high H+
-Directly inhibits gastrin secretion
-Indirectly inhibits histamine release vi gastrin
-Stimulates somatostatin release - inhibits parietal cell activity

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19
Q

What 4 things in the duodenum affect gastric acid secretion in intestinal phase?

A

-Duodenal distension
-Low luminal pH
-Hypertonic luminal contents
-Presence of amino acids and fatty acids

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20
Q

How does the intestinal phase affect gastric aid secretion (mechanism)?

A

-Trigger release of enterogastrones:
-Secretin - inhibits gastrin release, promotes somatostatin release
-Cholecystokinin (CCk)
-Short and long neural pathways, reducing ACh release

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21
Q

Label this diagram:
What does it show?

A

Which substances affect the transporter protein of gastric acid secretion through secondary messengers

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22
Q

Label this diagram:

A
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23
Q

What is a peptic ulcer and some causes?

A

-An ulcer is a breach in a mucosal surface
-Causes:
-Helicobacter pylori infection
-Drugs - NSAIDS
-Chemical irritants - alcohol, bile salts, dietary factors
-Gastrinoma

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24
Q

what are 4 ways that a gastric mucosa can defend itself?

A

-Alkaline mucus
-Tight junctions between epithelial cells
-Replacement of damaged cells
-Feedback loops

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25
Describe what most commonly causes a peptic ulcer:
-Helicobacter pylori -Lives in gastric mucus -Secretes urease - splits urea into CO2 + ammonia -Ammonia + H+ = ammonium -Ammonium, secreted proteases, phospholipases and vacuolating cytotoxin A damage gastric epithelium -Inflammatory response -Reduced mucosal defence
26
What are NSAIDs and how do they cause peptic ulcers?
-Non-steroidal anti-inflammatory drugs -Mucus secretion stimulated by prostaglandins -Cyclo-oxygenase 1 needed for prostaglandin synthesis -NSAIDs inhibit cyclo-oxygenase 1 -Reduced mucosal defence
27
What is needed for prostaglandin synthesis and what does a lack of this cause?
-Cyclo-oxygenase 1 -NSAIDs inhibit cyclo-oxygenase 1 -reduced mucosal defence as mucus secretion is secreted by prostaglandins
28
How do bile salts cause peptic ulcers?
-Duodeno-gastric reflux -Regurgitated bile strips away mucus layer -reduced mucosal defence
29
How do you treat peptic ulcers caused by Helicobacter pylori?
-Eradicate the organism -Triple therapy: 1 - proton pump inhibitor 2 - antibiotics
30
What cells produce pepsinogen and what mediates its production?
-Chief cells -Mediated by input from enteric nervous system (ACh) -Secretion parallels HCl secretion
31
What is pepsinogen? What is the science name for this?
Inactive form (zymogen) of pepsin enzyme
32
Where is pepsinogen activated?
Luminal activation to pepsin
33
What is pepsinogen activation dependant on?
-pH dependant -Most efficient when pH<2 -Positive feedback loop - pepsin also catalyses the reaction
34
Under what conditions is pepsin active? When is it inactivated?
-Pepsin is only active at low pH -Irreversible inactivation in small intestine by HCO3-
35
Label this diagram: What does it show?
36
What is pepsin's role in protein digestion?
-Accelerates protein digestion -Breaks down collagen in meat - helps shred meat into smaller pieces with greater surface area for digestion
37
Is pepsin essential for protein digestion, why?
-Not essential - protein digestion can occur if the stomach is removed -Normally accounts for around 20% of total protein digestion
38
What is the stomach volume when empty and full?
-Empty stomach has volume of around 50mL -When eating it can accommodate around 1.5L with little luminal pressure increase
39
What does smooth muscle in the stomach body and fundus undergo when empty/full?
Receptive relaxation
40
What is gastric motility coordinated by?
-Receptive relaxation mediated by parasympathetic nervous system acting on enteric nerve plexus -Coordination - afferent input via vagus nerve -Nitric oxide and serotonin released by enteric nerves mediate relaxation
41
What is peristalsis?
Wave like muscle contractions that move food through the digestive tract
42
Where does peristalsis begin?
-Peristaltic waves begin in gastric body -Weak contraction in body - little mixing
43
What is the second stage of peristalsis?
-More powerful contraction in gastric antrum -Pylorus closes as peristaltic waves reach it
44
What is the third stage of peristalsis?
-Little chyme enters duodenum -Antral contents forced back towards body (mixing)
45
What determines the frequency of peristaltic waves?
-Determined by pacemaker cells in muscularis propria and is constant (3/minute) -Interstitial cells of Cajal
46
Describe the basic electrical rhythm of the stomach:
-Pacemaker cells undergo slow depolarisation-repolarisation cycles -Depolarisation waves transmitted through gap junctions to adjacent smooth muscle cells -Do not cause significant contraction in empty stomach
47
Do the strength of peristaltic contractions vary, why?
-Yes -Excitatory neurotransmitters and hormones further depolarise membranes -Action potential generated when threshold reached
48
What two things can increase the strength of peristaltic contractions?
-Gastrin -Gastric distension (mediated by mechanoreceptors)
49
Name six things that decrease the strength of peristaltic contractions:
-Duodenal distension -Increase in duodenal luminal fat -Increase in duodenal osmolarity -Decrease in duodenal luminal pH -Increase in sympathetic NS action -Decrease in parasympathetic NS action
50
When does gastric emptying happen?
Capacity of stomach > capacity of duodenum
51
What causes dumping syndrome? Name some symptoms:
-Overfilling of duodenum by a hypertonic solution -Vomiting -Bloating -Cramps -Diarrhoea -Dizziness -Fatigue -Weakness -Sweating
52
Label this diagram:
53
What is gastroparesis and what can cause it?
-Delayed gastric emptying -Drugs -Abdominal surgery -Parkinson's disease -Multiple sclerosis -Scleroderma -Amyloidosis -Female gender
54
What is the term for delayed gastric emptying?
Gastroparesis
55
What are 6 symptoms of gastroparesis?
-Nausea -Early satiety -Vomiting undigested food -GORD -Abdo pain/ bloating -Anorexia
56
What does the bilaminar disc develop from?
The inner cell mass
57
Describe gastrulation:
-Primitive streak forms on epiblast -Epiblast cells migrate to primitive streak and invaginate through it -Some cells displace hypoblast and form endoderm -Some cells create new layer between the epiblast and endoderm = mesoderm -Epiblast = ectoderm
58
What structures develop from the ectoderm?
-CNS and PNS -Skin, hair and nails -Pituitary gland, sweat glands, tooth enamel
59
What structures develop from the mesoderm?
-Muscle, cartilage and bone -Urogenital system, spleen and adrenal cortex -Connective tissue of gut wall, pancreas and liver -Visceral peritoneum
60
What structures develop from the endoderm?
-Epithelium of Gi tract, respiratory tract -Hepatocytes (liver cells) -Endocrine and exocrine cells of pancreas
61
What does this diagram show?
-Lateral folding
62
what does this diagram show?
-Cephalo-caudal folding -Close of gut tube along its length except for connection that remains between midgut and yolk sac - vitelline duct > narrows and degenerates during gestation -Closure of ventral body wall complete except at connecting stalk > umbilical cord
63
Label the mesoderm on this diagram:
64
What are three conditions due to failure of ventral body wall to close?
-Thoracic region: Ectopia cordis -Abdomen: Gastroschisis -Pelvic region: Bladder exstrophy
65
When does the gut tube start to differentiate?
-Whilst lateral folding is bringing the ventral body wall together
66
What specifies the different parts of the gut tube?
-Concentration gradient of retinoic acid -Lowest cranially -Highest distally -Differential expression of transcription factors and genes along the tube specify how regions will develop
67
Label this diagram: What does it show?
Differentiation of the gut tube
68
What is in the foregut and its derivatives?
-Foregut: -Oesophagus -Stomach -First half of duodenum -Derivatives: -Liver -Pancreas -Mesenteries: -Dorsal mesentery -Ventral mesentery
69
Describe the ventral mesentery (embryology):
-Arises from septum transversum -Liver grows into it and splits it into 2: -Lesser omentum - connects liver to stomach and duodenum -Falciform ligament - connects liver to anterior abdominal wall
70
Describe the oesophagus (embryology): What is the difference in nerve innervation?
-Upper 2/3 - striated muscle innervated by vagus nerve -Lower 1/3 - smooth muscle innervated by splanchnic nerves -Lung bud appears at ventral wall of foregut in the 4th week - become separated from each other
71
What abnormal development can occur during oesophageal development?
-Oesophageal atresia - +/- tracheoesophageal fistula (abnormal connection)
72
How and when does the stomach form?
-This section of gut tube starts to dilate in week 4 -Changes shape due to different rate of growth of different parts -Changes position - rotates 90 degrees clockwise around its long axis: left side to lie anteriorly and right side posteriorly -Brings duodenum to right
73
How does the liver develop (first stage)?
-Liver bud is an outgrowth from the distal foregut (endoderm epithelium) -Appears in week 3 -Cells proliferate - grow into septum transversum -Connection between liver bud and foregut (duodenum) narrows > bile duct
74
How does the liver develop (second stage)?
-Small outgrowth from the bile duct > gallbladder -As liver grows, remaining mesoderm either side becomes membranous > falciform ligament and lesser omentum
75
How does the pancreas develop?
-Dorsal and ventral buds arise from duodenum -Dorsal bud develops in dorsal mesentery -Rotation of the stomach swings ventral bud posteriorly -Dorsal and ventral buds fuse
76
How does the lesser sac form?
Rotation forms small space behind the stomach - lesser sac
77
# Stomach Dorsal mesentery Rotation Posterior abdominal wall Lesser sac What are the final positions of the foregut viscera?
-Rotation of the stomach brings it to left side and anterior and swings duodenum to right -Dorsal mesentery along greater curvature bulges down and grows - greater omentum - becomes fixed to mesentery of transverse colon (and posterior wall) -Rotation alters the position of mesenteries, omenta and peritoneal ligaments -Some organs brought into contact with posterior abdominal wall - pancreas and duodenum and become retroperitoneal -Small space behind stomach is formed - lesser sac
78
What does the spleen develop from?
Dorsal mesentery
79
What are the functions of saliva?
-Lubricant for mastication, swallowing and speech -Oral hygiene -Wash -Immunity - antibacterial/antiviral/antifungal -Buffer
80
What pH does the oral cavity need to be maintained at and how?
-Around 7.2 -Range of around 6.2-7.4 -Bicarbonate/carbonate buffer system for rapid neutralisation of acids
81
What is needed for taste?
Aqueous solvent for digestive enzymes required for taste
82
What does dysfunction of the salivary glands associate with?
-Oral pain -Infections -Increased risk of dental caries
83
What is the flow rate of saliva production?
0.3 to 0.7ml per minute
84
What volume of saliva is secreted in adults and from where?
-Daily secretion of 800-1500ml in adults -From major and minor glands
85
What is in the serous secretion of saliva?
-Alpha amylase -Starch digestion
86
What is in the mucus secretion of saliva?
-Mucins -Lubrication of mucosal surfaces
87
What kind of secretion does the parotid gland produce?
Serous
88
What kind of secretion is produced by submandibular and sublingual glands?
Both mucous and serous
89
What kind of secretion do minor salivary glands produce?
Mainly mucous
90
What 8 things affect the composition and amount of saliva produced?
-Flow rate -Circadian rhythm -Type and size of gland -Duration and type of stimulus -Diet -Drugs -Age -Gender
91
What is saliva?
Secretion of proteins and glycoproteins in a buffered electrolyte solution
92
What are the major contributions of saliva to oral health?
-Lubrication - mucous coat -Mechanical coat - flow -Buffering salts - neutralise acids -Remineralisation - Ca2+ and PO43- -Defensive and digestive function - proteins
93
How many proteins and peptides have been detected in saliva?
-3652 proteins -12,562 peptides
94
What proportion of salivary proteins and peptides are also contained in serum?
-51% of proteins -79% of peptides
95
What 3 things provide defence in the mouth?
-The mucosa - physical barrier -Palatine tonsils - lymphocyte subsets + dendritic cells - immune surveillance and resistance to infection -Salivary glands - saliva washes away food particles, bacteria or viruses might use for metabolic support
96
How do salivary glands link to immunity?
-Salivary glands are surrounded by lymphatic system - linked to thoracic duct and blood -Broad range of immune cells -Oral mucosa and glands have high blood flow rate
97
Which glands are continuously active and which aren't?
-Continuously active - Submandibular, sublingual and minor glands -Not - Parotid
98
What becomes the main source of saliva and when?
-Parotid gland -No measurable unstimulated secretion -Main source of saliva when stimulated -SMG glands main source of unstimulated saliva
99
What does whole saliva contain?
-Salivary gland secretions -Blood -Oral tissues -Microorganisms -Food remnants
100
What could saliva be used for and how?
-Diagnosis instead of blood samples -salivary TB biomarkers are worth the search to evaluate their ability to differentiate between TB disease states
101
What is the basic structure of salivary glands?
-Composed of two morphologically and distinct epithelial tissue -Acinar cells around -Ducts - collect to form large duct entering the mouth
102
What are salivary glands equipped with (similar to other glands)?
Channels and transporters in the apical and basolateral membranes enabling transport of fluid and electrolytes
103
What are the two types of acini?
Serous and mucous acini
104
Describe serous acini:
-Dark staining -Nucleus in basal third -Small central duct -Secrete water + alpha amylase
105
Describe mucous acini:
-Pail staining - "foamy" -Nucleus at base -Large central duct -Secrete mucous (water + glycoproteins)
106
What are the two larger ducts of the salivary glands?
-Intralobular ducts -main excretory duct
107
What do intralobular ducts divide into?
-Intercalated: -Short narrow duct segments -Cuboidal cells that connect acini to larger striated ducts -Striated: -Striated like a thick lawn -Major site for reabsorption of NaCl
108
Label this diagram: What does it show?
Salivary gland
109
Label this diagram:
110
Describe 3 things about striated salivary ducts:
-Appear striated at basal end -Basal membrane highly folded into microvilli for active transport of HCO3 against concentration gradient -Microvilli filled with mitochondria for energy to facilitate active transport
111
What is this?
Striated salivary duct
112
Do the salivary ducts just facilitate the transport of saliva?
No
113
what is the function of the salivary ducts?
-Primary saliva - Rich in NaCl and isotonic plasma-like fluid secreted by acini -Electrolyte composition is modified in duct system -Ducts secrete K+ and HCO3- and reabsorb Na+ and Cl- -epithelium of duct doesnt allow any water movement so final saliva becomes saliva
114
What does epithelium of salivary ducts not allow and why?
-Not allow any water movement -Final saliva becomes hypotonic
115
What are salivary glands a good target for?
Valuable target tissue for both systemic and upper GI tract gene therapeutic applications
116
What are the advantages of salivary glands (6)?
-Well encapsulated - limit undesirable vector spread -Nearly every luminal membrane easy to access - non-invasive -Ductal access of SG uses limited fluid volume - not diluted or disseminate during deliver - low vector dose -Epithelium well differentiated and slowly dividing - stable cell-population for vectors -Large protein export production -Single Sg not crucial to life and can be removed
117
What are the 2 general pathways for protein secretion of salivary glands?
-Predominant leading to saliva (mucosal; across apical membrane) -Constitutive leading mainly towads interstitium and bloodstream (serosal; across basolateral membrane)
118
What can entry into regulated salivary secretion be saturated by and how is it overcome??
Overexpression of transgene product and "overflow" can exit via constitutive into bloodstream
119
How can salivary hypofunction be overcome?
-hAQP-1 cDNA transfer into duct epithelial cells -Codes water channel - plasma membrane protein that facilitates rapid transmembrane water movement in response to osmotic gradient -Duct cells generate osmotic gradient (lumen>interstitium) that water could follow
120
What can cause salivary hypofunction?
-Radiation therapy -RT damage - fluid secreting acinar cells leaves water-impermeable duct cells -Normal saliva duct reabsorbs NaCl secreted by acinar cells in isotonic primary salivary fluid
121
How many main salivary glands are there?
-Three pairs of main salivary glands -Parotid -Submandibular -Sublingual
122
What percentage of salivary flow do main salivary glands provide?
80%
123
Where are minor salivary glands?
-Submucosa of oral mucosa -Lips -Cheeks -Hard and soft palate -Tongue
124
What percentage of salivary flow is provided by minor salivary glands?
20%
125
What do parotid glands contain?
Serous acini
126
What do submandibular salivary glands contain?
-Mixed -Serous and mucous acinini -referred to as seromucous
127
What do sublingual salivary glands contain?
-Mixed -More mucous acini
128
Where are parotid salivary glands?
-Superficial triangle outline between: -Zygomatic arch -Sternocleidomastoid -Ramus of mandible + masseter and med pterygoid
129
Where is the parotid duct?
-Stenson's duct -Crosses masseter -Pierces buccinator and enters oral cavity at 7/7 -Palpate a finger's breadth below zygomatic arch
130
Label this diagram:
131
What does the parotid salivary gland look like horizontally?
triangular outline with apex on carotid sheath
132
What 3 things pass through the parotid salivary gland?
-External carotid artery + terminal branches -Retromandibular vein -Facial nerve + branches to muscles of facial expression (MFE) -(PAROTID CAPSULE VERY TOUGH)
133
What are parotid glands almost entirely made of?
-Serous acini -Ducts interspersed
134
What are the two lobes of the submandibular salivary gland separated by?
Mylohyoid muscle
135
What are the two lobes of the submandibular salivary gland?
-Larger superficial lobe -Smaller deep lobe in floor of mouth
136
What is the path of the submandibular duct?
-Wharton's duct -Begins in superficial lobe -Wraps around free posterior border of mylohyoid -runs along floor of mouth and empties into oral cavity at sublingual papillae
137
Label this diagram: What does it show?
Opening of ducts at sublingual papillae
138
What is the histology of the submandibular salivary gland?
-Mixed gland of serous and mucous acini -Some serous acini arranged as crescent-shaped groups of glandular cells at bases of mucous acini -Referred to as serous demilunes
139
Where is the sublingual salivary gland?
Between mylohyoid muscle and oral mucosa of the floor of the mouth
140
Label this diagram:
141
Describe sublingual salivary glands and their drainage:
-Variable in size with mixed acini -Mainly mucous acini -No large duct - drains into submandibular duct and/or small ducts that pierce oral mucosa on the floor of the mouth
142
Label this diagram:
143
Where are minor salivary glands found?
-Concentrated in bucal labial, palatal and lingual regions -Also found: -Superior pole of tonsils (Weber's glands) -Tonsillar pillars -Base of tongue (von Ebner's glands)
144
What is the histology of minor salivary glands?
-All minor salivary glands are mucous except serous glands of von Ebner -Lack branching network of draining ducts - each salivary unit has its own simple duct
145
What stimulation causes the production of saliva?
-Parasympathetic nerve stimulation causes production of a copious flow of saliva -Sympathetic stimulation causes secretion of protein and glycoprotein
146
What are 5 causes of salivary gland disease and dysfunction?
-Obstructive -Inflammatory -Degenerative -Drug side effects -Cancer
147
What is xerostomia and causes?
-Dry mouth -May be consequence of CF or Sjogrens syndrome -Most common causes: -Medication -Irradiation for head and neck cancers -High prevelence of caries and candida infections
148
What is obstruction to salivary glands?
-Saliva contains calcium and phosphate ions that can form salivary calculi (stones) -Most often in submandibular glands (80%) -Block duct at bend round mylohyoid or at exit at sublingual papillae
149
What is inflammation of salivary gland and causes?
-Infection secondary to blockage -Causes: -Mumps (viral infection): -Fever, malaise -Swelling of glands -Pain especially over parotid because capsule does not allow much enlargement
150
What is degenerative condition of salivary glands?
-Complications of radiotherapy to head and neck for cancer treatment -Sjogren's syndrome -Mainly post-menopausal females -Also affects lacrimal glands -rheumatoid arthritis may also be present
151
Describe drug side effects on salivary glands:
-Most common dysfunction encountered -500 prescription drugs have sympatheticomimetic effect -Act on NA receptors or inhibit parasympathetic action at ACh receptors
152
At what point will a patient experience xerostomia?
If salivary output falls to <50% of normal flow
153
What are the consequences of salivary gland dysfunction?
-Low lubrication - oral function difficult -Low (natural) oral hygiene - poor pH control -Accumulation of plaque -> rampant dental caries, gingivitis and periodontal disease -Opportunistic infections esp. fungal infections (candida = thrush)
154
Label this diagram: What does it show?
Movement of glucose
155
Label this diagram: What does this show?
Processing of glucose in the liver
156
Label this diagram: What does it show?
Movement and process of glucose in skeletal muscles
157
Label this diagram: What does it show?
Glucose processing in the brain
158
Label this diagram: What does it show?
Metabolism of glucose in RBC
159
Label this diagram: What does it show?
Metabolism of glucose in adipocytes
160
Label this diagram: What does it show?
Metabolism of amino acids
161
Label this diagram: What does it show?
Absorption of lipids
162
Summarise the metabolism of fuels in the fed state:
-Fuels oxidised for energy -Any excess stored: -Triglycerides in adipose -Glycogen in liver and muscle
163
Label this diagram: What does it show?
Glucose metabolism during short fasting
164
Label this diagram: What does it show?
Glucose metabolism during long fasting
165
Label this diagram: What does it show?
Fat metabolism during fasting
166
Label this diagram: What does it show?
Prolonged fasting
167
What substances to do with energy metabolism can be measured?
168
How can you describe insulin and glucagon and what processes show this?
-Insulin is anabolic -Glucagon is catabolic
169
What are the effects of cortisol on fuel metabolism?
Preparation for stress response
170
What are the effects of adrenaline on fuel metabolism?
Fight or flight response
171
What are the effects of thyroxine on fuel metabolism?
172
What are the effects of growth hormone on fuel metabolism?
173
Describe the energy balance for fuel metabolism:
174
What would each of these energy balances produce?
175
What 3 things contribute to obesity?
176
What does this describe and how does it change with obesity?
-Leptin -Released by adipocytes
177
What does this describe?
-Ghrelin -Produced by stomach
178
What two hormones control apetite?
-Ghrelin increases apetite -Leptin decreases apetite
179
What are 4 diseases associated with metabolic problems?
-Diabetes -Lipid disorders -Malabsorption / processing of nutrients -Obesity
180
What are 7 functions that the liver performs?
-Carbohydrate metabolism -Fat metabolism -Protein metabolism -Hormone metabolism -Toxin/drug metabolism and excretion -Storage -Bilirubin metabolism and excretion
181
Label this diagram: What does it show?
Iron metabolism
182
What is ferritin?
-Large spherical protein -Consists of 24 noncovalently linked subunits -Subunits form a shell surrounding a central core
183
How many atoms of iron are in a ferritin core?
Up to 5000 atoms of iron
184
Where is ferritin found?
-Cytoplasm of cells -Also found in serum
185
What is the concentration of ferritin related to?
Concentration of ferritin is directly proportional to the total iron stores in the body
186
What two groups of disorders can cause ferritin excess?
-Excess iron storage disorders -Non-iron overload
187
What are 5 examples of excess iron storage disorders that can cause ferritin excess?
-Hereditary haemochromatosis -Haemolytic anaemia -Sideroblastic anaemia -Mulitple blood transfusions -Iron replacement therapy
188
What are 4 non-iron overload disorders that can cause ferritin excess?
-Liver disease -Some malignancies -Significant tissue destruction -Acute phase response: -Inflammation -Infection -Autoimmune disorders
189
What is the only known cause of ferritin deficiency and what can it result in?
-Iron deficiency -Can result in anaemia: -Ferritin less than 20ug/L indicated depletion -Ferritin less than 12ug/L suggests a complete absence of stored iron
190
How are vitamins usually provided?
In the diet
191
What is RDA?
Recommended daily allowance
192
What is AI?
-Adequate intake -Where no evidence to determine RDA
193
What are 3 things that vitamins can act as?
-Gene activators -Free-radical scavengers -Coenzymes or cofactors in metabolic reactions
194
What can excess vitamin ingestion cause?
Can result in toxicity
195
What is the difference between water-soluble and fat-soluble vitamins?
-Water soluble vitamins pass more readily through the body -They require more regular intake than fat-soluble vitamins
196
What are 4 examples of fat-soluble vitamins?
-A -D -E -K
197
What are 2 examples of water-soluble vitamins?
-B -C
198
How do we source retinal?
-Ingest directly from meat -Produce retinal from carotenes
199
What is the chemical name group of vitamin A?
Retinoids
200
What are 5 sources of retinols?
-Meat (liver) -Dairy -Egga -Supplements -Fortified cereals
201
What are 4 sources of carotenoids?
-carrots -Spinach -Swede -Tomatoes
202
What is the daily requirement for intake of vitamin A?
-Men: 0.6 mg/day -Women: 0.7mg/day
203
What are 4 functions of vitamin A?
-Vision -Used to form rhodopsin in rod cells of retina -Reproduction -Spermatogenesis in males -Prevention of foetal resorption of female -Growth -Stabilisation of cellular membranes
204
Describe vitamin A deficiency:
-Rare in affluent countries as vitamin A levels drop when liver stores severely depleted -Fat malabsorption can cause it -Clinical features: -Night blindness -Xeropthalmia -Blindness
205
What are symptoms of acute vitamin A excess?
-Abdominal pain, nausea and vomiting -Severe headaches, dizziness, sluggishness and irritability -Desquamation of skin
206
What are symptoms of chronic vitamin A excess?
-Joint and bone pain -Hair loss, dryness of the lips -Anorexia -Weight loss and hepatomegaly
207
What is carotenemia and what is it a cause of?
-Reversible yellowing of the skin -Does not cause toxicity -Vitamin A excess
208
What are 3 functions of vitamin D?
-Increased intestinal absorption of calcium -Reabsorption and formation of bone -Reduced renal excretion of calcium
209
What does a vitamin D deficiency cause?
-Demineralisation of bone: -Rickets in children -Osteomalacia in adults
210
Where is vitamin E stored?
-Non-adipose cells such as liver and plasma -Labile (readily available) and fixed pool
211
Is vitamin E important?
-Yes -Important antioxidant
212
What are the daily intake requirements of vitamin e?
-Men: 4 mg/day -Women: 3 mg/day
213
What 3 things can cause a vitamin E deficiency?
-Fat malabsorption (e.g. cystic fibrosis) -Premature infants -rare congenital defects in fat metabolism (e.g. abetalipoproteinanaemia)
214
What are 5 clinical manifestations of vitamin E deficiency?
-Haemolytic anaemia -Myopathy -Retinopathy -Ataxia -Neuropathy
215
What are the symptoms of vitamin E excess?
-None -Vitamin E excess is relatively safe in excess
216
How is vitamin K absorbed and stored?
-Rapidly taken up by the liver -Transferred to very low-density lipoproteins and low density lipoproteins which carry it in the plasma
217
What are 3 sources of vitamin K?
-Vitamin K1 (phylloquinone) -Synthesised by plants and present in food -Vitamin K2 (menaquinone) -Synthesised in humans by intestinal bacteria -Synthetic vitamin K's -K3 (menadione) -K4 (menadiol)
218
What are 2 functions of vitamin K and how is it assessed?
-Responsible for activation of some blood clotting factors -Needed for liver synthesis of plasma clotting factors: -II -VII -IX -X -Assessed by measuring prothrombin time
219
What are 2 causes of vitamin K deficiency?
-Haemorrhagic disease of newborn -Vitamin K injection given to newborn babies -Rare is adults, unless on warfarin
220
What are consequences of vitamin K excess?
-K1 relatively safe in excess -Synthetic forms are more toxic -Can result in oxidative damage, red cell fragility and formation of methaemoglobin
221
What are common sources of vitamin C?
Fresh fruit and vegetables
222
What is the daily recommended intake of vitamin C for adults?
40 mg/day
223
What are 3 functions of vitamin C?
-Collagen synthesis -Antioxidant -Iron absorption
224
What does vitamin C deficiency cause?
-Scurvy -Easy bruising and bleeding -Teeth and gum disease -Hair loss
225
Describe vitamin c treatment:
-Improves symptoms quickly -Joint pain gone within 48 hours -Full recovery within two weeks
226
What can excess vitamin C cause?
-Doses > 1g/day can cause Gi side effects -No evidence that increased vitamin C reduces the incidence or duration of colds
227
What did the first clinical trial look at?
Different daily treatments that contain vitamin C and their outcomes
228
What is another name for vitamin B12?
Cobalamins
229
What are the two active forms of vitamin B12?
-Methylcobalamin -5-deoxyadenosylcobalamin
230
How is vitamin B12 digested and absorbed in the body?
-Released from food by acid and enzymes in the stomach -Binds to R protein to protect it from stomach acid -Released from R proteins by pancreatic polypeptide -Intrinsic factor (IF) produced by the stomach needed for absorption -IF-B12 complex absorbed in terminal ileum -B12 stored in liver
231
What are 3 potential causes of vitamin B12 deficiency?
-Pernicious anaemia -Autoimmune destruction of IF-producing cells in stomach -Malabsorption -Lack of stomach acid -Pancreatic disease -Small bowel disease -Veganism
232
What are 2 symptoms of vitamin B12 deficiency?
-Macrocytic anaemia -Peripheral neuropathy in prolonged deficiency
233
What are common dietary sources of folate?
Found in many foods fortified with folic acid
234
Who has higher requirements of folate intake?
Pregnant women
235
What are 3 functions of folate?
-Coenzyme in methylation reactions -DNA synthesis -Synthesis of methionine from homocysteine
236
What are 3 causes of folate deficiency?
-Malabsorption -Drugs that interfere with folic acid metabolism (anticonvulsants, methotrexate) -Disease states that increase cell turnover (leukemia, haemolytic anaemia, psoriasis)
237
What are 3 symptoms of folate deficiency?
-High homocysteine levels -Macrocytic anaemia -Foetal development abnormalities (neural tube defects)
238
What is the intrinsic pathway activated by?
Contact
239
What activates the extrinsic pathway?
FVII coming into contact with tissue factor
240
What does the coagulation cascade eventually result in?
Fibrin clot formation
241
Which 6 clotting factors are produced in the liver?
-I (fibrinogen) -II (prothrombin) -IV -V -VI -VII
242
What 3 things can be measured to test the performance of the clotting pathways?
-Prothrombin time (PT) (extrinsic pathway) -International normalised ratio (INR) -Activated partial thromboplastin time (aPTT) (intrinsic pathway)
243
What can a prolonged PT indicate?
Deficiency in the synthetic capacity of the liver
244
Is prolonged PT specific to liver disease?
-No, other causes: -DIC -Severe GI bleed -Some drugs -Vitamin K deficiency
245
Label this diagram of hormones regulating fuel metabolism:
246
What are xenobiotics?
-Foreign substances with no nutritional value -Serve no purpose -Need to be excreted, may be toxic if not excreted in time -Can cause damage to cell protein, lipids or DNA
247
Give a brief description of liver detoxification:
-Oxidation in phase I reactions - Cytochrome P450 enzymes -Conjugation in phase II reaction (for renal excretion) -Active metabolites of a drug -Ethanol detoxification
248
What group of enzymes have been found to play a large part in detoxification?
Cytochrome P450 enzymes
249
What are the 2 main types of xenobiotic biotransformation reactions and what are their functions?
-Phase I and phase II -Purpose of making the compounds non-toxic and water -soluble
250
What kind of reactions happen in phase I and phase II reactions?
251
What kind of reactions happen in phase I and phase II reactions and how is hydrophillicity affected?
252
What is this? Describe its structure:
-Paracetemol -Acetyl group attached to amine group attacked to phenol in the para-position -para-acetylaminophenol
253
What does this show? What are its properties?
-para-acetylaminophenol glucuronide -glucoronyl group has many OH groups making it polar to facilitate excretion in the urine
254
Where does most detoxification take place?
Liver
255
What are 4 mechanisms of detoxification in the liver?
-Inactivation and facilitated elimination of drugs and other xenobiotics -Formation of active metabolites with similar or occasionally enhanced activity -Activation of pro-drugs -Toxification of less toxic xenobiotics
256
Where does most biotransformation in the liver take place?
-Within the endoplasmic reticulum -Often SER
257
How many groups of cytochrome P450 enzymes are there and by how many genes are they coded by (superfamily)?
-10 main groups of cytochrome P450 enzymes -55 genes
258
What features do all P450 enzymes have in common?
-All present in the SER - hence called microsomal enzymes -Oxidise the substrate and reduce oxygen -Have reductase subunit which uses NADPH -They are inducible - enzyme activity may be increased by certain drugs, some dietary components and some environmental toxins -Generate a reactive free radical compound
259
How are cytochrome P450 enzymes subdivided into families?
-According to amino acid similarity -Important: CYP3A4, CYP2D6
260
Why is CYP3A4 important?
-Involved in metabolism of about 50% of clinically prescribed drugs -Accounts for 1/3 of cytochrome enzymes in liver
261
Explain induction and genetics in terms of cytochrome P450 enzymes:
-Induction - one drugs can induce numerous cytochrome isoenzymes -Genetics - note genetic variation especially in CYP2D6
262
What 3 medications are metabolised by CYP3A4?
-Paracetemol -Codeine -Diazepam
263
What 2 medications are metabolised by CYP2D6?
-Amitriptyline -Codeine
264
Can a medication be metabolised by more than one cytochrome enzyme?
-YES (important) -Codeine is an important example
265
What do reactions catalysed by cytochrome P450 enzymes start with?
-Start with cytochrome P450 reductase (auxillary enzyme) -It transfers hydrogen (and e-) from NADPH to cytochrome P450
266
In drug and alcohol metabolism, where is cytochrome P450 bound?
-Phospholipid membrane (SER) -Attached to a reductase -Cytochrome P450 has active site and haem component for oxygen binding
267
What is the second stage of cytochrome P450 reactions?
-Elemental O2 enters the reaction and oxygen is the electron acceptor -2 oxygen molecules have different fate -Hydrogen used by cytochrome P450 to reduce one of the oxygen atoms to water -Other oxygen retained in a highly reactive form, used to force one or the other reaction on the substrate -Most commonly forms a OH group
268
What is this?
Fe-heme group of cytochrome P450
269
What is one of the most commonest mechanisms of drug interactions?
Via cytochrome P450
270
What may accelerate or inhibit the breakdown of some medications?
-Induction of cytochrome P450 enzymes due to drug interactions -Enzymes may be inhibited by various drugs and foodstuffs (usually take quicker effect than induction) -Can result in increased blood concentrations of certain medications -Drugs can compete for the active site on cytochrome P450 enzymes -Drugs with higher affinity will be metabolised faster
271
What does this show?
-Cytochrome P450 (CYP3A4) induction via phenobarbital -Phenolbab binds to a receptor in the cytoplasm -Receptor migrates to the nucleus while bound to suitable compound (phenolbarb) -Enhances mRNA formation
272
What does this show?
-Clozapine inducers can affect cytochrome P450 -Clozapine levels increase after cessation of smoking and decrease for smokers -Dose of clozapine may need to be altered to avoid toxicity or for it to be affected -Shows how factors such as smoking affect liver metabolism
273
What inducers affect clozapine?
-Barbiturates -Carbamazepine -Primidone -Rifampicin -Cruciferous vegetables, e.g. cabbage, broccoli -Grilled meat -Smoking (Increased metabolism of drugs)
274
What agents inhibit cytochrome P450, increasing concentrations of medications such as clozapine?
Ciproflaxacin
275
Why is grapefruit juice significant in cytochrome P450 enzymes?
-Cytochrome P450 enzymes inhibited by dietary components -A lot of medications metabolised in phase I by CYP3A4 -Most statins metabolised by CYP3A4 -Inhibiting metabolism of simvastatin and atorvastatin, grapefruit juice causes increased blood levels with increased side effects
276
What are 4 common pathways of detoxification including drug metabolism and what do they show?
-Active drug to inactive metabolite -Active drug to active metabolite -Inactive drug to active metabolite -Active drug to reactive intermediate (Products have been neutralised)
277
What does this show?
-Inactivation of a xenobiotic (Active drug to inactive metabolite) -OH group added -OH group conjugated with glucuronic acid or sulphate resulting in product sufficiently polar to be excreted by kidneys -Due to the fact excretion of unmodified drug id very slow as it is non-polar and mainly dissolves in fat with little in the plasma
278
Describe active drug to active metabolite conversion:
-Active drug may be converted to another active form -Codeine metabolised into morphine -Codeine is morphine molecule with one hydroxyl group replaced by methyl group making it less susceptible to first pass metabolism -Codeine is active and is de-methylated in the liver to morphine which is also active
279
What does this show?
-Active drug to active metabolite -CYP3A4 de-methylates to active metabolite norcodeine -5-10% acted on by CYP2D6 to produce morphine
280
Describe pro-drug to active drug metabolism:
-Inactive drug or pro-drug may be converted in liver to active agent -Loratadine is pro-drug of desloratadine - largely responsible for antihistaminergic effects of parent compound
281
Describe active drug to reactive intermediate metabolism:
-Drug converted into possibly toxic intermediate -Benzopyrenes (incomplete combustion of organic matter) converted into epoxides -Subsequent reaction with DNA is major mechanism of carcinogenesis in smokers -Reaction is of benzopyrenes with CYP1A1to produce epoxides
282
What is paracetamol metabolism an example of?
-Active drug to reactive intermediate -Active drug metabolised into harmful reactive intermediate -Also called acetaminophen -CYP2E1 produces harmful intermediates
283
Describe paracetamol metabolism at therapeutic doses:
-Usually only 5-10% is metabolised via the cytochrome P450 system to NAPQI -Then metabolised to harmless products that can be excreted in the urine -At therapeutic dose, NAPQI is quickly metabolised and inactivated by G-SH
284
Describe paracetamol metabolism at overdose:
-G-SH overwhelmed -Well over 5-10% is metabolised by cytochrome enzymes producing excess NAPQI -Toxic NAPQI builds up, causing liver cell damage
285
Describe 6 Phase II reactions:
-Glycoside conjugation - glucuronidation -Sulphate - sulphation -Glutathione -Methylation -Acylation -Phosphate conjugation -TOP TWO MOST COMMON
286
What are phase II reactions?
-Conjugation reactions -Make the compound more water-soluble -Glucuronyl, sulphate and phosphate groups are polar and make the molecule ready for excretion via urine
287
What are responsible for most phase II reactions?
-Transferase enzymes -Uridine diphosphoglucuronosyl transferase (UGT) -N-acetyl transferase (NAT) -Glutathione S-transferae (GST) -Sulphotransferase (ST)
288
Describe microsomal enzymes: -Location -Sites -Enzymes -Reactions -Note
-Location - SER -Sites - Liver the kidney, lungs, intestinal mucosa -Enzymes - mono-oxygenases (CYPs, FMOs); UGTs -Reactions - majority of drug biotransformation reaction; oxidative, reductive and hydrolytic and gluronidation -Note - INDUCIBLE by drugs, diet
289
Describe non microsomal enzymes: -Location -Sites -Enzymes -Reactions -Note
-Location - cytoplasm and mitochondria of hepatocytes, other tissues -Sites - protein oxidases, esterases, amidases, conjugases -Enzymes - protein oxidases, esterases, amidases, conjugases -Reactions - non-specific enzymes that catalyse few oxidative, a number of reductive and hydrolytic - conjugation other than glucuronidation -Note - not inducible but having polymorphism
290
Is ethanol metabolised via phase I or II
-Doesn't fit either -Doesn't need to be conjugated for excretion -2% to 10% is excreted in urine - used in liver as dietary fuel -Major route via alcohol dehydrogenase (ADH)
291
What is the role of the microsomal system of ethanol metabolism?
-Microsomal Ethanol Oxidising System (MEOS) -Predominantly CYP2E1 -Produces acetaldehyde as intermediate (toxic) -CYP2E1 has high affinity for alcohol (MEOS is combined ethanol-oxidising activity of all CYP450 enzymes)
292
How does ethanol cause liver damage?
-If liver's ability to oxidise acetaldehyde is overwhelmed, it accumulates in the liver -Contributes to alcohol-induced hepatitis by forming adducts with amino acids -Also binds to glutathione and predisposes cells to damage by peroxides and other free radicals
293
What is acetaldheyde metabolised to in the liver and by what?
-Acetate -Acetaldehyde dehydrogenase producing NADH
294
What are the 3 functions of the colon?
-Absorption of water and electrolytes (osmosis) -Excretion of waste (motility) -Production of vitamins (microbiome)
295
Label this diagram of the large intestine:
296
Label this diagram: What does it show?
Different layers of the colon
297
What are the muscular layers to the colon?
-Continuous circular muscle -3 "ribbons" of longitudinal muscle - taeniae coli
298
What are the 3 "ribbons" of longitudinal muscle of the colon called?
Taeniae coli
299
What is the basic histology of the colon?
-Simple columnar epithelium -Goblet cells
300
What is the nerve supply of the colon?
-Enteric nervous system (Intrinsic) -Myenteric plexus -Submucosal plexus -Extrinsic nervous system -Parasympathetic -Sympathetic
301
What makes up the enteric nervous system of the colon?
-Myenteric plexus -Submucosal plexus
302
Label this diagram: What does it show?
The anal sphincter
303
What are the 4 basic phases of defecation?
1. Basal 2. Pre-expulsive 3. Expulsive 4. Termination
304
Describe the basal phase of defecation:
-Colon - segmental contractions (mixing) -Rectum - motor complexes (keeps rectum empty) -"braking mechanism" -Anal sphincter - tonic contraction -Puborectalis - contracted (90o angle)
305
Describe the pre-expulsive phase of defecation:
-Colon - high amplitude propagating contractions -Mass movement of stool (8 times a day) -Gastro-colic reflex -Rectum - fills causing distension -Rectal compliance (adaptive relaxation) -Anal sphincter - EAS maintains contraction -Reflex relaxation of IAS - stool sampling -Puborectalis - remains contracted
306
Describe the expulsive phase of defecation:
-Rectum contracts -IAS, EAS and PR relax -Valsalva manoeuvre/posture aid emptying
307
Describe the termination phase of defecation:
-Traction loss causes sudden contractions of EAS -"closing reflex" -Valsalva ceases -Change in posture (to standing)
308
Label this diagram: What does it show?
Parasympathetic defecation reflex
309
What are 4 disorders of defecation causing constipation?
-Consistency of stool -Bowel motility -Physical blockage to the bowel -Pelvic floor disorders
310
What are 4 disorders of defecation that cause diarrhoea?
-Consistency of stool or frequency of movements -Diseased bowel mucosa -Reduced rectal capacity -Pelvic floor disorder
311
Why are plain abdominal x-rays of limited use?
-Abdominal anatomy is more complex than thoracic anatomy -Most abdominal tissue is of similar density - difficult to differentiate -Equivalent ionising radiation as 4 months of background radiation
312
What are common uses of abdominal x-rays?
-Looking for foreign bodies -Dilated loops of bowel (sign of intestinal obstruction)
313
How does Computed Tomography (CT) work?
-Directing very large dose of x-rays at patient from various angles -Reproduce images digitally producing 3D images -Scroll through series of images to see each part of the abdomen
314
Is CT commonly used, any drawbacks?
-Frequently used -Much greater dose of ionising radiation -CT of abdomen and pelvis exposes patient to equivalent of approximately 4.5 years of background radiation
315
What are common uses of CT scans?
-Widely used in abdominal imaging for many pathologies -Very often used with contrast
316
What is contrast (abdominal imaging)?
-Contrast agents are radio-opaque liquids -Increase differentiation between different tissues -Iodine and barium (x-rays/CT) -Gadolinium (MRI)
317
How can contrast agents enter the body?
-Swallowed -Inserted into the GI tract via rectum before x-rays or CT scan -Not absorbed - later excreted via the anus
318
How can contrast agents visualise blood vessels?
-Injected into veins or arteries during x-rays, CTs or MRIs -Help radiologist to identify inflammation, cancer, blockage of blood vessels and bleeding -Filtered out of blood by kidneys and excreted in urine
319
What are common uses of contrast in abdominal imaging?
-Barium swallow -Barium enema -CT abdomen with contrast -CT aortogram -Trauma CT
320
Are ultrasound (US) scans useful?
-Very frequently used -Images not as useful as CT as they are 2D images -Less detailed
321
How does ultrasound work?
-Sounds waves of higher frequency than human hearing -Directed from probe towards target structure -Reflected off structure and received back at probe -Time taken and amplitude of rebound detected and used to calculate densities and depths of structures -Images viewed in real-time and probe can be placed where needed to view desired organ
322
What are the advantages and disadvantages of ultrasound?
-Non-ionising so theoretically cause no harm to the patient -fairly difficult to perform and interpret, specialist training is needed
323
What are common abdominal uses of ultrasound?
-Liver -Gallbladder -biliary tree -Aorta -Kidneys -Bladder volume -Vascular access -Fluid in abdomen
324
Describe endoscopy:
-Very frequently used -Visualise lumen of hollow organs using camera -Non-ionising but may need sedation and risk of perforation -Capsule endoscopy - pill-sized camera swallowed
325
What are common uses of endoscopy?
-Visualise lumen and walls of oesophagus -Stomach -Small and large intestine -Looking for bleeding or foreign bodies
326
What is laparoscopy?
-Keyhole surgery -Small finger sized holes in anterior abdominal wall and inserting cameras to visualise peritoneal cavity -Can be used to just have a look but can be procedural -Commonly used to visualise abdominal and pelvic organs
327
Label the small and large bowel:
328
What are the maximum 'normal' diameters of the small intestine, large intestine and caecum?
-3,6,9 rule -SI - 3cm -LI - 6cm -Caecum - 9cm -Larger suggests dilated bowel and possible obstruction
329
What is different about CT scans?
-Produced a series of images, not a single image like a plain x-ray -May need to scroll through images to view different planes
330
Label these abdominal CT scans:
331
Label this diagram:
332
What does terrestrial mean?
-Not living in an aqueous solution filled with nutrients -Humans are terrestrial
333
What have humans adapted for optimum nutrient absorption?
-Specialised gut tube through the body for getting nutrients to the circulatory system for delivery to tissues -Organisation of shapes that maximise surface area for exchange
334
Label this diagram: What does it show?
Overview of GI processes
335
What is the function of the GI tract?
-Take relatively large solids and digest them into smaller molecules that can be absorbed as nutrients -Serve as a barrier to toxins, bacteria, parasites, etc.
336
What is the functional anatomy of the GI system (5)?
-GI system is a hollow organ - tube through body -Lumen is 'outside' the body's tissues but its environment is tightly controlled by the body -Specialised organs for secretion of enzymes and bile -Epithelial cells line entire GI and serve as primary barrier -Structure maximises surface area for secretion and absorption (folds, villi, crypts)
337
What is a key feature of the GI tract?
-Transport of fluid and electrolyte is a key function of the GI tract -Epithelial cells may: -Secrete water and electrolytes -Absorb water and electrolytes
338
Label this diagram of daily gut fluid balance:
339
How are H2O and electrolytes moved in the GI system?
-Water moves down osmotic gradient -Electrolytes move down electrochemical gradient -To move against a conc gradient = energy -Energy is supplied by sodium gradients (generated by sodium pumps) and by proton gradients
340
What does this diagram show?
-Paracellular = in between cells -Transcellular = through cells -Even though there are tight junctions, movement of water and ions can still occur in between cells -Majority is transcellular
341
How much fluid does the small intestine absorb a day?
7.5 L/day
342
How long is the small intestine?
Around 6m
343
Where in the small intestine does net absorption and net secretion take place?
-Net absorption = villi -Net secretion = crypts
344
What does this show?
Normal villi
345
Label this diagram of nutrient absorption: How does it work?
-Na+ couples nutrient absorption -2 stage transcellular process: -1st stage - membrane transport protein -2nd stage - Na+/K+ ATPase transporter -Water follows due to osmosis
346
Label this diagram: what does it show?
intestinal secretion
347
What 4 things affect absorption in the GI system?
-Number and structure of enterocytes -Blood and lymph flows -Nutrient intake -GI motility
348
What 3 things affect the secretion in the GI system?
-Irritants -Bile -Bacterial toxins
349
What 2 factors can affect Gi motility and secretion in the GI system?
-Hormonal -Neural
350
What are 3 clinical manifestations of disorders affecting GI absorption and secretion?
-Diarrhoea -Weight loss -Failure to thrive
351
What does this show and what can cause it?
-Damaged villi -Coeliac disease
352
Describe toxin-induced diarrhoea:
-Cholera toxin released from bacteria into infected intestine -Binds to intestinal cells -Stimulates adenylate cyclase to produce cAMP -Dramatic efflux of ions and water -Watery diarrhoea
353
How do oral rehydration salts work?
-Water passively follows the osmotic gradient -SGLT1- sodium glucose co-transporter moves Na and glucose from luminal membrane into enterocyte -Water follows
354
What is the definition of digestion and its two parts?
-Breakdown of large, complex organic molecules that can be used by the body -Mechanical - chewing, churning -Chemical - enzymes
355
What three groups of macronutrients are digested?
-Carbohydrates -> monosaccharides -Protein -> amino acids -Fats - > fatty acids/glycerol
356
Where is the primary site for digestion and absorption of food?
Small intestine
357
How does digestion occur in the GI lumen?
By secreted enzymes and on the surface of enterocytes by membrane-bound enzymes
358
How does absorption occur in the small intestine?
-Simple diffusion -Facilitated diffusion -Active transport -Endocytosis -Paracellular transport
359
How is the surface area of the small intestine increased?
-Greatly increased by extensive folding -Projection of fingerlike villi covered with microvilli
360
Label this diagram: What does it show?
Digestion of carbohydrates
361
Label this diagram: What does it show?
-Absorption of digested carbohydrates -Enterocytes absorb glucose and galactose -Through an Na-dependent secondary active transport process -Fructose is absorbed through facilitated diffusion
362
Label this diagram:
363
Label this diagram:
364
How are fats digested?
-Fat and water tend to separate -Enzymes in water can't get at the fat -Bile (emulsifier) arrives -Has affinity for both fat and water and can therefore bring fat into the water -After emulsification, fat is mixed in the water solution -Fat-digesting enzymes have access to it
365
Where are bile acids released and moved?
-Released into the small intestine -After function performed - recycled back to the liver -97% recycled
366
Label this diagram of fat absorption in the small intestine:
367
368
369
370
371
What are 4 functions of saliva?
-Lubricates, cleans oral cavity -Dissolves chemicals -Suppresses bacterial growth -Digest starch by amylase
372
Label this diagram:
373
Label this diagram:
374
Label this diagram:
375
What do mucous neck cells produce + function?
376
What do parietal cells produce + function?
377
What do enterochromaffin-like cells produce + function?
378
What do chief cells produce + function?
379
What do D cells produce + function?
380
What do g cells produce + function?
381
Describe the first phase of gastric secretion regulation:
Cephalic phase
382
Describe the second stage of gastric secretion regulation:
383
Describe the third stage of gastric secretion regulation:
384
What are the 2 functions of the pancreas?
-Endocrine function: -Secretes insulin and glucagon from islets of Langerhans -Exocrine function: -Secretion of pancreatic juice
385
What 3 things regulate pancreatic secretions?
386
What are the main components of the exocrine secretion of the pancreas?
-Aqueous bicarbonate secretion -Enzyme secretion
387
What. are the average diameters of the pancreatic duct in each section of the pancreas?
-Tail - 1mm -Middle - 2mm -Head - 3-4mm DISTENSION SUGGESTS BLOCKAGE IN THE PANCREATIC DUCT
388
Label this diagram of pancreatic cells:
389
Label the different cell types of the pancreas:
390
Label the different functions of the different parts of the pancreas:
391
What is the rate of bicarbonate secretion in the pancreas and by what cells?
-1 litre/24 hours -Epithelial cells in pancreatic duct produce HCO3- and H2O -Resting phase maintains a low flow - predominantly Na+ and Cl- -High flow rates Na+ and HCO3-
392
What is the function of the bicarbonate secretion produced by the pancreas?
-Protects duodenal mucosa by neutralising stomach acid -Buffers duodenal contents to optimise pH for enzyme digestion
393
What initiates protein digestion?
Initiated by pepsin in the stomach
394
Where does a majority of protein digestion occur and by what?
-Small intestine -Pancreatic proteases: trypsin and chymotrypsin
395
How are trypsin and chymotrypsin stored?
-Stored as proenzymes: -trypsinogen -chymotrypsinogen -Trypsinogen activated by enterokinase -Trypsin activates chymotrypsinogen and additional trypsinogen
396
Can triglycerides be absorbed across intestinal mucosa?
No
397
How are lipids digested?
-Lipases hydrolyse triglycerides to monoglycerides and free fatty acids -Bile salts aid triglyceride digestion and absorption of monoglycerides and free fatty acids
398
What is fat digestion dependent on?
Pancreatic and hepatic secretion
399
What is orlistat?
Pancreatic lipase inhibitor
400
Describe the role of amylase:
-Hydrolyses starch to maltose (glucose-glucose disaccharide) and maltotriose (trisaccharide) and limit dextrins -Pancreas is major source of amylase -salivary amylase has a small role
401
What are 4 other examples of digestive enzymes?
-Ribonuclease -Deoxyribonuclease -Gelatinase -Elastase
402
What is pancreatic enzyme secretion like during cephalic stage?
-Vagal innervation and gastrin -Low level stimulus in anticipation of a meal -Water, bicarbonate and enzymes released
403
What is pancreatic secretion like during intestinal stage?
-Secretin -Cholecystokinin -Gastrin -Release water, bicarbonate and enzymes
404
405
406
407
What three hormones control pancreatic secretion?
-Cholecystokinin -Secretin -Gastrin
408
What is the endocrine function of the pancreas and why is it important?
-Insulin and glucagon secretion -Vital for carbohydrate and lipid metabolism
409
What are 4 symptoms on pancreatic exocrine insufficiency?
-Maldigestion -Diarrhoea -Steatorrhoea -Weight loss
410
What are 4 consequences of pancreatic exocrine insufficiency?
-Malnutrition -Oesteoporosis -Increased cardiovascular morbidity -Symptom burden
411
What are 4 factors in an assessment of pancreatic function?
-History, risk factors -Imaging -Faecal elastase -Markers of malnutrition
412
What is the treatment of PEI? (pancreatic exocrine insufficiency)
-Pancreatic enzyme replacement therapy -STOP smoking -Bone health assessment -Treat underlying cause
413
Why is bile important (3)?
-Lipid digestion and absorption -Cholesterol homeostasis -Excretion of lipid soluble xenobiotics/drug metabolites/heavy metals
414
What is bile?
-Complex lipid-rich micellular solution -Water -Inorganic electrolytes -Organic solutes (bile acids, phospholipids, cholesterol, bile pigment)
415
What is the daily production of bile?
500-600mls per day
416
What does formation of bile depend on?
-Hepatic synthesis and cannalicular secretion of bile acids -Bile acids = major organic anion in bile
417
What is the maintenance of hepatic bile formation essential for?
Normal liver function
418
What is the turnover rate of bile?
-Most bile acids (95%) secreted by hepatocytes have been previously secreted into intestine -Enterohepatic circulation
419
Label this diagram:
420
What are bile acids synthesised from and where?
-Cholesterol -Hepatocytes of the acini
421
What are the primary bile acids and what are they synthesised from + their properties?
-Cholic acid (CA) - water soluble -Chenodeoxycholic acid (CDCA) - water soluble -Cholesterol - lipophilic
422
What happens to primary bile acids before secretion and why?
-Cholic acid (AC) and Chenodeoxycholic acid (CDCA) are conjugated before secretion into bile canaliculus -N-acyl amidated with glycine or taurine -Enhances hydrophilicity and acidic strength of side chain -pKa = 5.0 unconjugated -pKa = 3.9 glycine conjugate, 2.0 taurine conjugate
423
What does conjugation do to the movement of bile acids?
Decreases passive diffusion of bile acids across membranes during transit through EHC (keeps intraluminal)
424
Describe the classical pathway of bile acids:
425
What properties do bile acids have and what does this do?
-Amphipathic - hydrophilic and hydrophobic parts -Reduce surface tension and aid emulsification
426
l=Label the parts of the bile acid:
427
Describe emulsification:
-Fat is insoluble in water -Emulsification increases surface area for lipolysis -Stable emulsion important for close apposition of lipase and triglycerides -Lipases act at surface of emulsified droplet and liberate FA from glycerol backbone (lipolysis)
428
Explain the process of absorption of fatty acids and glycerol:
429
Explain the emulsification and digestion of lipids
430
What is the pathway of chylomicrons?
431
What are the first 3 functions of bile acids?
-Induce bile flow (osmotic effect) and secretion of biliary lipids (Pl and cholesterol) -Digestion of dietary fats - solubilising lipids and lipid digestion products as mixed micelles facilitating aqueous diffusion across intestinal mucosa -Facilitates protein absorption - accelerating hydrolysis by pancreatic proteases
432
What are the second 3 functions of bile acids?
-Cholesterol homeostasis - facilitates dietary absorption/elimination as BA are water-soluble end-products of cholesterol catabolism, indice bile flow and solubilise cholesterol enabling movement from hepatocytes -> lumen of intestine -Antimicrobial (physiochemical + inducing anti-microbial genes) -Prevents calcium gallstones and oxalate renal stones
433
Label this diagram of nitrogen metabolism:
434
Label this diagram of nitrogen metabolism:
435
Label this inputs and outputs of this system in the liver:
436
What are the most common donor/acceptor pairs?
437
Label this diagram of the movement of amine groups: Describe it:
Alpha-keto-acid can be used in citric acid cycle for glucose production (GLUCONEOGENESIS)
438
Label the inputs and outputs of the glucose alanine cycle:
439
Label the glucose alanine cycle: What does it do?
-Alanine principal ammonia transporter -Pyruvate recycled into glucose -Gluconeogenesis takes place in liver and not muscle to conserve ATP for contraction
440
What enzymes are used as an indicator for liver cell damage?
-Aminotransferase enzymes -AST, ALT -Higher levels = higher leakage from cells
441
Label the urea cycle: Describe it:
-One turn of cycle consumes 3 ATP equivalents and 4 high energy nucleotides (PO4-) -Urea is only compound generated all others are regenerated
442
What is the name for this? Label it:
Kreb's bicycle
443
Label the diagram of the movement of amine during the glucose-alanine cycle:
-Alanine transaminated -Pyruvate can be used in krebs for gluconeogenesis -Glutamate can be oxidatively deaminated
444
What happens to glutamate cycles during low energy times? Why?
-alpha-ketoglutarate can be fed into citric acid cycle so hepatocytes can upregulate GDH in times of energy depletion -ADP drives reaction due to energy depletion -Reverse when ATP is in excess -NH3 can be converted into urea for excretion
445
Label the glutamine synthase reaction: Why is it done?
-Produces amino acid -Suitable for incorporation into proteins -Principal role is principal ammonia carrier -Mostly found in blood, non-toxic
446
Label the glutaminase reaction: Why is it done?
-Mitochondrial enzyme so seperate to glutamate synthesis -Liver is neither net consumer or producer of glutamine -Liver can scavenge ammonia that hasn't been incorporated into urea -Ammonia is controlled by incorporation into either glutamine. orurea
447
What is transamination?
Chemical reaction transferring an amine group from an amino acid to a ketoacid to form a new amino acid
448
What does this show?
-High levels of ammonia associated with neurotoxicity -Ammonia can cross blood-brain barrier very easily -Converted to glutamate by glutamate dehydrogenase -Alpha-ketoglutarate depletes and so does Krebs -Irreparable cell damage and cell death
449
How is the embryonic gut tube formed?
-Connection between gut and yolk sac -Dorsal mesentery forms
450
What are the 5 stages of midgut development?
1. Elongation 2. Physiological herniation 3. Rotation 4. Retraction 5. Fixation
451
Describe the first step of midgut development:
-Elongation -Elongation -> formation of primary intestinal loop -Connection to yolk sac (vitelline dict) maintained but narrows
452
What are the two parts of the primary intestinal loop?
-Cephalic limb -Caudal limb
453
What does the cephalic limb go on to form?
-Distal part of duodenum -Jejunum -Part of ileum
454
What does the caudal limb go on to form?
-Distal part of ileum -Caecum -Appendix -Ascending colon -Proximal 2/3 transverse colon
455
Describe the second part of midgut development:
-Intestinal loops herniate (move into) into umbilical cord - 6th week -Abdominal cavity too small for gut loops and liver -Gut loop starts to rotate -90o anticlockwise at axis of SMA
456
Describe the third stage of midgut development:
-Rotation -Anticlockwise from front -First 90o during herniation -Brings caudal limb more cranially
457
What happens at the end of the third stage of midgut development?
-Continued elongation -Elongation continues -Part destined to become small intestine develops coils -Large intestine part elongates but doesn't coil
458
Describe the fourth stage of midgut formation:
-10th week gut loop returns to abdomen -Gut loop roates further 180o anticlockwise -Total rotation = 270o
459
What does retraction lead to in midgut development?
-Starts to position gut -Jejunum 1st to left side -Ileum follows to right -Caecum returns LUQ -Caecum descends to RIF, ascending colon to right
460
Describe the fifth stage of midgut development:
-Some mesenteries close contact with posterior abdominal wall and fuse/fix -Considered 'retroperitoneal' -fascial layer (toldt fascia) develops between parietal peritoneum on posterior body wall and visceral peritoneum on organ
461
What is this?
462
What are the final positions of midgut viscera after development?
-Jejunum + ileum central, jejunum UL, ileum LR -Ileum enter caecum on right -Caecum descend RIF -Ascending + Descending colon fix posterior body wall -Dorsal mesentery SI rotate around SMA with gut loop
463
Describe the movement of the caecal bud and appendix:
-Once gut returns to abdomen, caecal bud first in RUQ -Descends to RIF and ascending colon lengthens -Appendix develops during descent - comes to lie in a variety of postions
464
Describe appendicitis referred pain:
-Umbilicus, T10 -Part of midgut so sympathetic supply (motor) from lesser splanchnic nerve - T10-11 spinal cord levels -Visceral sensory fibres return to cord and brain from midgut to same levels -Brain interprets pain as coming from umbilicus skin
465
Describe the first part of hindgut formation:
-Boundary between endoderm lining cloaca and surface ectoderm is cloacal membrane -urorectal septum grows towards cloacal membrane and separates allantois from cloaca
466
Describe the second stage of hindgut formation:
-Ectoderm of cloacal membrane invaginates to form anal pit - lower part of anal canal -Cloacal (anal) membrane ruptures - upper and lower anal canal continuous -Upper and lower different blood supplies due to different origins

Phase 1 (23 decks)

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