Week 2 Flashcards
1
Q
What 4 factors need to be considered when undertaking a medical elective in resource poor countries?
A
- Stay within your competence
- Maintain ethical standards
- Develop “cultural competence” (Bowman, 2011)
- Minimise burden on host country & healthcare system
2
Q
Who is classed as a child and young person?
A
Under 18 in England, Wales and NI
Under 16 in Scotland
Children = People who aren’t mature enough to make important decisions for themselves
3
Q
When a child lacks capacity, who makes the decision?
A
Parents
BUT decisions are constrained by best interests of the child. If not then wishes can be overridden.
Note: If assent can be given, it should be sought
4
Q
As well as clinical best interest, what else should be considered?
A
a. the views of the child or young person
b. the views of parents
c. the views of others close to the child or young person
d. the cultural, religious or other beliefs and values of the child or parents
e. the views of other healthcare professionals involved in providing care
to the child or young person
f. which choice, if there is more than one, will least restrict the child or young person’s future options.
5
Q
Name 2 cases in which there was conflict due to doctors and parents disagreeing?
A
Case 1: Re S (Parents - Jehovah’s Witnesses)
S was 4 1⁄2 years old with T cell leukemia
Undergoing chemotherapy & blood transfusion would improve recovery
Parents refused (religious & safety reasons) Refusal overruled
Case 2: Re A (Jodie & Mary, conjoined twins)
- If they remained together, they would both die
- If separated, Jodie would live, Mary would die
- Doctors wanted to act to separate, parents did not allow
- High court, then court of appeal
- Separation took place
6
Q
What does “Gillick Competent” mean?
A
A young person under 16 with capacity to make any relevant decision
7
Q
How is competence determined?
A
Understand, retain, use/weight this information and communicate decision
8
Q
Explain, using either the lock/key or flak jacket analogy, why treatment can go ahead, even if a young person does not give their consent?
A
Consent is often more easily accepted than refusal. Why?
– Key & lock analogy (then, flak jacket)
– Doctor needs only 1 key to unlock “consent”
– 3 keys potentially exist in the case of the mature minor:
• Mature minor
• Parents (right co-exists)
• Courts
9
Q
Outline the Hannah Jones as a mature minor case?
A
Upheld refusal of heart transplant after long term illness
13yrs old
PCT sought court order for heart transplant for 13 yr old girl (she had refused to undergo the transplant – her parents agreed with her decision)
Child protection officer said Hannah was adamant.
Refusal respected
(Note: agreed to transplant the following year, and is currently doing well)
10
Q
What are the laws on living children organ donors?
A
Scotland: Under 16’s cannot be living donors
England, Wales and NI: Solid organ donation by living children is permitted
BMA were opposed, now support so long as young person is competent to give valid consent and is not under coercion
11
Q
What are the euthanasia laws for children in Europe?
A
In the Netherlands, euthanasia is legal for those over the age of 12 (with permission of their parents) - the Dutch Paediatric Association has now called for age limit to be lifted altogether (June 2015)
Belgium lifted all age restrictions in 2014
12
Q
What are the ethical issues surrounded children and clinical research?
A
For:
-Research with children is crucial if children themselves are to benefit from the best possible treatment when they are ill.
Against:
- Whether parents should or ought to allow their young children to participate in research that involves even minor discomfort or distress to,
- The question of whether parents or children should have a right to participate in research – a right, for example, that may be claimed where a child is very seriously ill and a new, as yet-unlicensed, treatment is seen as being their ‘only hope
13
Q
What is the eu regulation regarding generics and bioavailability?
A
Generics must have a bioavailability of 80-125% compared to the reference product (EU reg.)
14
Q
What is generic substitution?
A
Generic substitution occurs when a different formulation of the same drug is substituted. All generic versions of a drug are considered by the licensing authority to be equivalent to each other and to the originator drug.
15
Q
What is therapeutic substitution?
A
Therapeutic substitution is the replacement of the originally-prescribed drug with an alternative molecule with assumed equivalent therapeutic effect. The alternative drug may be within the same class or from another class with assumed therapeutic equivalence
16
Q
Name the advantages and disadvantages of drug administration via oral route?
A
Advantages – Cheap – Safe – Convenient Disadvantages – Patient compliance – Variation in bioavailability of drug
17
Q
Particle size and formation, what is contained in a drug capsule?
A
Drug Excipients Binding agents Lubricants Coatings
18
Q
List the advantages of the different forms of oral route: Buccal / sublingual mucosa Gastric mucosa Small intestine Large intestine / colon Rectal mucosa
A
Buccal / sublingual mucosa – Direct absorption into bloodstream – Avoids first pass metabolism – Not ideal surface for absorption Gastric mucosa – Enteric coating Small intestine – Main site of drug absorption – Large surface area, more neutral pH Large intestine / colon – Poor absorption, long transit times Rectal mucosa – Direct to systemic circulation
19
Q
4 ways small molecules cross cell membranes
A
1) Diffusing directly through the lipid
-Lipid solubility highly important
2) Diffusing through aqueous pores
-More likely important for diffusion of gases
3) Transmembrane carrier protein
– e.g. solute carriers
4) Pinocytosis
– Mostly macromolecules, not drugs
20
Q
What is the physicochemical factor affecting drug absorption?
A
Drug ionisation
21
Q
What is the henderson-hasselblach equation for a weak base?
A
pKa - pH = Log10 [BH+]/[B]
ionised on top
22
Q
What is the henderson-hasselblach equation for a weak acid?
A
pKa - pH = Log10 [AH]/[A-]
note ionised on bottom
weak acid are more likely to be absorbed by SI than weak bases
23
Q
Weak acid are ____likely to be absorbed by SI than weak bases
A
weak acid are more likely to be absorbed by SI than weak bases
24
Q
Effect of food on gastric emptying?
A
Slows the rate
25
Effect of decreased absorption on drug absorption
Intestinal motility
Interactions with food, acids
Presystemic metabolism
26
Effect of delayed absorption on drug absorption
Gastric emptying
Clinically important
Cmas may decrease
27
Increased absorption effect on drug absorption
Poorly water soluble drugs
increased solubilisation
Decreased pre systemic metabolism
28
What is process of first pass metabolism in levodopa uptake?
Levodopa: Prodrug in treatment of Parkinson's disease
Rapidly taken up from stomach and small intestine. Large neural amino acid transport carrier (LNAA)
DOPA decarboxylase present in gastric mucosa
29
Effect of intestinal disease in drug absorption?
Altered rate of drug absorption due to disease state
– E.g. Increased GI motility, compromised GI integrity
– What about reduced motility? (e.g. diabetic gastroparesis)
E.g. Crohn's and coeliac disease
30
Factors that affect oral absorption?
1. Particle size and formulation
2. GI motility
3, First pass metabolism
– First pass metabolism by gut wall or hepatic enzymes
4. Physicochemical factors
– Direct drug interactions, dietary factors, varying pH
5. Splanchnic blood flow
– Increased flow increases drug absorption
6. Efflux pumps
– P-glycoprotein
31
Name 2 parenteral routes and their properties?
Subcutaneous:
Slow absorption due to blood flow
Intramuscular:
-Lipophilic drugs rapidly
-Polar drugs via bulk flow and endothelial cell junctions
-High MTW or very lipophilic drugs via lymphatics
32
What determines the rate of onset when using parenteral routes?
Extent of capillary perfusion
Drug vehicle
Affected by factors that alter perfusion
33
Inhalation as a method of drug administration:
Where is the drug absorbed via?
Systemic effects?
Local effects achieved by:
Where is the drug absorbed via: Alveolar epithelium and bronchial mucosa
Systemic effects:
-Lipid-soluble drugs
-Drugs of abuse
-Accidental poisoning
Local effects achieved by:
-Modifying structure e.g. ipratropium
-Changing the particle size e.g. salbutamol
-Selectivity for receptors e.g. salbutamol
-Rapid breakdown in circulation e.g. fluticasone
34
Intranasal drug administration:
Advantages?
Limitations?
Advantages:
- Easily accessible
- Rich vascular plexus
- Avoids hepatic first pass metabolism
- Ease, convenience, safety
Limitations:
-Limited drugs suitable as it requires concentrated drug
35
What are the local and systemic uses for drug administrations via the topical route?
Local uses:
- Corticosteroids for eczema e.g. hydrocortisone
- Antihistamines for insect bites e.g. mepyramine
- Local anaesthetics
Systemic uses:
- Transdural patches (HRT, GTN, nicotine)
- Accidental poisoning (AChEsterase insecticides)
36
What are the physicochemical factors of drugs and how does it impact its absorption?
```
Weak bases:
-Ionised in acidic pH
-Absorbed in SI
-Ionisation in plasma
Weak acids
- Unionised in acidic pH
-BUT also absorbed in small intestine due to large SA
```
37
What is the embryological reasoning behind the falciform ligament and lesser omentum having free, inferior borders?
The ventral mesentery just ends about half-way along the duodenum
38
```
Foregut:
Extends from what to what?
Supplied by which vessel?
Gives rise to which structures?
What may occur on abnormal tracheo-oesophageal development?
```
The foregut extends from the mouth to just distal to the developing liver
Supplied by Coeliac trunk; refers pain to epigastrium (T7 to 9)
Foregut gives rise to the: oesophagus (which gives the respiratory diverticulum that forms the trachea and lungs); stomach; proximal duodenum; liver and biliary system; pancreas; and spleen
Abnormal tracheo-oesophageal development gives rise to TO fistula etc (or TEF, American esophagus)
39
Describe the sequence of events during the formation of the stomach from the foregut
By the 4th week of development the stomach appears – dilation of foregut
It rotates about both a longitudinal and an AP axis:
- 90 degrees clockwise around the longitudinal axis so the left side faces anteriorly, and lesser curve faces to the right, while greater curve faces left
- AP axis so the pyloric part comes to lie on the right and oesophago-gastric junction slightly left, so that the greater curve faces left and inferior
40
Describe the sequence of events during the formation of the duodenum from the foregut
The duodenum forms from the foregut and beginning of midgut
Initially it is found in the midline but the rotations of the stomach also cause the duodenum to rotate and swing to the right
It then “falls” on to the posterior abdominal wall and becomes retroperitoneal
During development the duodenum lumen becomes obliterated by a proliferation of cells, then it is re-canalized
41
Describe the sequence of events during the formation of the liver and gallbladder from the foregut
3rd week
The liver develops from an endodermal bud, it penetrates the ventral mesentery and septum transversum and gives rise to the hepatic ducts and gallbladder
The ventral mesentery directly in contact with the liver becomes its visceral peritoneum and the bare area of the liver is where it contacts the diaphragm with no intervening peritoneum
42
Describe the sequence of events during the formation of the pancreas from the foregut
The pancreas forms from dorsal and ventral endodermal buds from the duodenum; the rotation of the latter causes the ventral bud to migrate around to lie behind and fuse with the dorsal bud so that the adult pancreas lies in the curve of the duodenum
The ducts of the dorsal and ventral buds unite to form the main pancreatic duct.
While the accessory duct is the remnant of the duct of the dorsal bud
43
How does an obstructive annular pancreas form?
In embryological developement of the foregut if the ventral pancreas may form as 2 lobes
44
As the stomach is rotated around it's longitudinal axis, what happens?
Its posterior aspect (that will become the greater curve) rotates to the left, so that the dorsal mesentery i.e. mesogastrium (that will become the greater omentum) is thrown to the left as well; and a potential space (omental bursa or lesser sac) is left posterior to the stomach and lesser omentum
45
What are the boundaries of the epiploic foramen?
Anteriorly: free border of the
lesser omentum, with the bile duct, the hepatic artery proper, and the portal vein
Posteriorly: inferior vena cava
Superiorly: caudate process of the caudate lobe of the liver
Inferiorly: first part of the duodenum
46
Boundaries and relations of the lesser sac
```
Anteriorly: caudate lobe
of liver; lesser omentum; stomach
Posteriorly: pancreas
Laterally: left kidney and adrenal gland;
on the right the epiploic
foramen
```
It extends upward as far as
the diaphragm and
downward it may extend a little way between the layers of the greater omentum
le
47
How is the greater omentum formed?
As the dorsal mesentery is thrown left, the stomach rotates on its AP axis and the greater curve faces inferiorly. The dorsal mesentery is then dragged with it so that a big, double-layered fold of mesentery, the greater omentum, hangs off the greater curve
48
Describe the sequence of events during the formation of the spleen from the foregut
Which two ligaments are formed, between which structures?
Spleen forms with the dorsal mesentery of the stomach
Lienorenal ligament: The mesentery between the spleen and the posterior abdominal wall (close to the kidney)
Gastrolienal / gastrosplenic ligament: the mesentery between the spleen and the stomach is the
49
Greater omentum overlies which structures?
Transverse colon and intestine
50
```
Midgut:
Commences and ends?
Supplied by?
By the 5th week...
Connected to the yolk sac via what?
Rapid growth leads to..
```
Commences immediately distal to the entrance of the bile duct into the duodenum and ends 2/3 along
transverse colon
Supplied by Superior Mesenteric Artery; pain refers to peri-umbilical region (T10)
By the 5th week the midgut is suspended from the dorsal abdominal wall as the primary intestinal loop
by a mesentery
It is connected to the yolk sac by the vitelline duct
Rapid growth of the intestinal loop causes its physiological herniation through the umbilicus and into the umbilical cord
51
The primary intestinal loop of the midway undergoes growth and rotation, describe
The cranial limb of the loop grows and will become much of the jejunum and ileum
The loop rotates in a counter clockwise direction
90degrees in the physiological hernia
And then another 180degrees as the loop drops back into the abdomen at about 70 days (10 weeks)
Overall this is a total of 270degrees of rotation around the axis of the SMA
52
Describe the migration of the caecum during midgut development?
Around 10 weeks
Initially, as the intestine drops back in to the abdomen, the jejunum lies to the left and the caecum is up in the right hypochondrium, adjacent to the liver
The caecum, with the appendix, then migrates inferiorly to the right iliac fossa
53
What two congenital abnormalities can occur in embryological development o the midgut?
Partial / abnormal rotation of intestine
Vitelline duct fistula- Leading faecal discharge at umbilicus
54
Name 3 conditions that occur during failure of recanalisation of GI tract?
Gastroschisis
Omphalocele
Umbilical hernia
55
Hindgut:
Gives rise to?
Supplied by?
Divisions of the cloaca?
Gives rise to: the distal end of the transverse colon (1/3); descending colon; sigmoid colon; rectum and upper 2/3 anal canal
Supplied by inferior mesenteric artery; refers pain to suprapubic region (T12)
The most inferior part of the hindgut develops from the cloaca, which is divided by the mesodermal uro-rectal septum:
Anteriorly the cloaca develops into the urogenital system
Posteriorly the anorectal canal
56
Describe the embryological development of the anal canal?
The distal aspect of the cloaca is closed by the anal membrane membrane
As the surrounding mesoderm and ectoderm proliferate, the anal part of the membrane sinks in to the anal pit
The membrane breaks down at 8 weeks, so that the proximal 2/3 of the anal canal is derived from the hindgut endoderm while the distal 1/3 is derived from ectoderm
The pectinate line marks the change in embryological derivation, blood and nerve supply
57
What causes an imperforate anus?
1. The common origin of the anal canal and the urogenital organs means that fistulae between them may
2. Also the anal membrane may not break down
Both causing an imperforate anus
58
What is Hirchsprung Disease?
Lack of normal development of the colonic innervation leads to a constricted, aganglionic segment of bowel, with a distended segment proximally (the innervation of which is normal)
59
Define the term psychosomatic disorder
Psychosomatic disorders are disorders where emotional or psychological factors can impact on the symptoms
60
Describe the signs and symptoms of irritable bowel syndrome (7)
* abdominal (stomach) pain and cramping, which may be relieved by defecation
* a change in bowel habits – such as diarrhoea, constipation, or sometimes both
* bloating and swelling of your stomach
* excessive wind (flatulence)
* occasionally experiencing an urgent need to go to the toilet
* a feeling that you have not fully emptied your bowels after going to the toilet
* passing mucus from your bottom
61
What is IBS?
Irritable bowel syndrome a common digestive condition
62
How is IBS diagnosed?
That in the last 3 months, with symptom onset at least 6 months prior to diagnosis the individual experiences recurrent abdominal pain or discomfort** at least 3 days/month in the last 3 months associated with two or more of the following:
• Improvement with defecation
• Onset associated with a change in frequency of stool
• Onset associated with a change in form (appearance) of stool
63
4 impacts of IBS on patients
* work?
* visits to health professionals
* Health Related Quality of Life (HRQoL)
* psychological health
64
IBS, causes?
* psychological disorders
* hyper-reactivity in the brain-gut interface
* infection
* food intolerance
* abnormal muscle contraction • serotonin receptors
65
Describe the common sense model of IBS
Health messages (such as abdominal pain, disturbed bowel habit) affected by:
- Gastrointestinal infections
- Food intolerances
- Abnormal guy physiology
Affect the cycle of coping procedures to deal with emotional reaction to life events and representation of illness risk.
Perceptions of treatment impact the emotional response to treatment.
66
IBS management, 4 main approaches?
1. Diet/ lifestyle (physical activity) changes approach
- Food diary: Monitor food intolerances, encourage healthy diet
- Assess activity levels
2. Drug treatments approach
- Treat the symptoms
3. Psychological approaches
- After 12 months
- Cognitive behavioural therapy
- Hypotherapy
- Psycholoical therapy
4. Complementary therapies approach
- Nutraceuticals
- Chinese herbal medicine
- Probiotics
67
What are the first line and second line drugs for treatment of IBS?
First line:
– Antidiarrhoeal (loperamide) – Laxatives (not lactulose)
– Antispasmodics
```
Second line:
– Laxatives (linaclotide)
– Antidepressants (second line)
• TCAs (if first line ineffective)
• SSRIs (if TCAs ineffective)
```
68
Outline the diet/lifestyles approach to treating IBS?
1. Diet/ lifestyle (physical activity) changes approach
- Food diary: Monitor food intolerances, encourage healthy diet
- Assess activity levels
69
Outline the drug treatments approach to treating IBS?
2. Drug treatments approach
- Treat the symptoms
First line:
– Antidiarrhoeal (loperamide) – Laxatives (not lactulose)
– Antispasmodics
```
Second line:
– Laxatives (linaclotide)
– Antidepressants (second line)
• TCAs (if first line ineffective)
• SSRIs (if TCAs ineffective)
```
70
Outline the psychological approach to treating IBS?
3. Psychological approaches
- After 12 months
- Cognitive behavioural therapy
- Hypotherapy
- Psycholoical therapy
71
Outline the complementary therapies approach to treating IBS?
4. Complementary therapies approach
- Nutraceuticals
- Chinese herbal medicine
- Probiotics
72
What is are the major functions of gastric motility? (3)
1. Allows stomach to act as a reservoir for the large volume of food ingested at a single meal
2. Breaks food into smaller particles and mixes with gastric secretions
3. Empties gastric contents into duodenum at controlled rate
73
Smooth muscle of the stomach:
3 layers?
Change in thickness?
3 layers:
Outer= Longitudinal
Middle= Circular
Inner= Oblique
Muscle wall thickness increases from proximal to distal
74
Innervation of the stomach:
Innervation from extrinsic nerves?
Enteric nervous system?
Sensory afferent fibres?
Rich innervation from extrinsic nerves
– Parasympathetic: Stimulate gastric smooth muscle motility and secretions
– Sympathetic: Inhibit motility and secretions
Enteric nervous system
–Myenteric plexus:
• Parasympathetic innervation via the vagus
• Sympathetic innervation via the coeliac ganglion
Sensory afferent fibres
–Between sensory receptors and the ENS (pressure, distension, pH, pain) and centrally via the vagal and splanchnic nerves
75
Discuss the receptive relaxation of the stomach and functions
The oral region has a thin muscular wall
Distension of the lower oesophagus induces relaxation of the lower oesophageal sphincter and the oral region of the stomach
Reduces pressure and increases volume of the stomach
76
What is the structure of the afferent and efferent information in the vasovagal reflex?
Afferent and efferent nerve fibres in the vagus
Afferent information: Mechanoreceptors associated with chewing, oesophageal and stomach distension relay information to CNS via sensory neurons
Efferent information from the CNS causes oral relaxation. The neurotransmitter, VIP (vasoactive intestinal peptide), released from postganglionic peptidergic vagal neurones is responsible for oral relaxation
77
Which region of the stomach is responsible for mixing?
Thick muscular wall of the CAUDAD REGION is responsible for mixing.
Contraction waves begin in the middle of the body, move distally with increasing strength towards the pylorus
Fundus and body muscle layers are thin.
78
What is the function of retropulsion in the stomach?
Propels gastric contents back for further mixing in the stomach
79
Control of slow wave frequency in the stomach
3-5 per minute
Neural and hormonal input DO NOT AFFECT slow wave frequency but do affect action potential frequency
Parasympathetic stimulation, gastrin and motilin INCREASE action potential frequency (and force of contraction)
Sympathetic stimulation and secretin DECREASE action potential frequency
80
What is the activity of the stomach during fasting?
Periodic gastric contractions (MMC's)
MMC= Migrating Myoelectric Complexes
These are mediated by motion released from endocrine cells in the upper GI tract at 90 min intervals.
Function: Clears stomach of residue remaining from previous meal
81
Why is gastric emptying rate regulated?
To ensure that gastric H+ is neutralised in the duodenum and there is adequate time for digestion and absorption of nutrients
82
Physical factors affecting gastric emptying? 3
1. Liquids empty more rapidly than solids
2. Isotonic fluids empty more rapidly than hypo- or hypertonic fluids
3. Solids must be reduced to particles < 1 mm3 or less. Retropulsion continues until this is achieved
83
Chemical factors inhibiting gastric emptying? 2
Presence of fat and H+ ions in the duodenum
Effect of fat: Mediated by cholecystokinin, secreted when fat reaches the duodenum
Effect of H+ ions: Mediated by reflexes in the enteric nervous system. H+ receptors in the duodenum detect low pH and relay information to the gastric smooth muscle via interneurons in the myenteric plexus
84
3 functions of the motility of the small intestine
1. Mixes chyme with digestive enzymes and pancreatic secretions
2. Exposes nutrients to the intestinal mucosa for absorption
3. Propels unabsorbed chyme into large intestine
85
Parasympathetic innervation of SI:
Nerve?
Action?
Neurotransmitter?
Nerve: Vagus
Action: Increases contraction
NT: ACh and motilin
86
Sympathetic innervation of SI:
Nerve?
Action?
Neurotransmitter?
Nerve: Coeliac and superior mesenteric ganglia
Action: Decreases contraction
NT: Noradrenaline
87
Slow waves in the small intestine:
Duodenum/ileum __ per min?
How? Why?
Duodenum: 12 per min
Ileum: 9 per min
MMC's occur every 90 minutes to clear the SI of residual chyme
88
What two forms contraction are coordinated by the ENS?
Segmentation for mixing
Peristalsis for forward movement:
- Orad contraction by ACh and substance P
- Caudad relaxation by VIP and NO
89
Structure of muscles and innervation of the colon?
Longitudinal muscle concentrated in 3 bands – Taeniae(tenia)coli
PARASYMPATHETIC
Vagus nerve:
- Caecum, ascending colon and transverse colon
- Stimulation causes segmental contractions of the proximal colon
Pelvic nerves:
- Descending and sigmoid colon, rectum and anal canal
- Stimulation causes expulsive contractions of the distal colon
SYMPATHETIC
• Stimulation stops colonic movements
90
Segmental contractions in caecum and proximal colon?
Contractions mix contents
Reverse peristalsis and segmental propulsion towards the caecum can occur.
[This retention favours Na+ and water absorption]
91
Large intestinal motility
* Material not absorbed in the small intestine enters the large intestine - faeces destined for excretion
* After contents of of the small intestine enter the caecum and proximal colon, the ileoceacal sphincter contracts. Faecal material moves from the caecum, through the colon to the rectum and on to the anal canal
* Colon receives 500 - 1500 ml of chyme per day but most of the salt and water are absorbed (100 ml per day lost in faeces)
* Contractions associated with sac-like segments called haustra (haustrations)
92
Mass movements in the colon due to..
Gastrocolin and duodenocolic reflexes
93
Two nerves in inguinal canal
Ilio-inguinal nerve
| Genito-femoral nerve
94
Deep inguinal ring at...
Mid point of inguinal ligament
95
Femoral pulse felt at....
mid inguinal point
96
Gastrocolic reflex?
Distension of the stomach by food increases the motility of the colon and the frequency of mass movements in the large Intestine
Afferent limb in the stomach mediated by the parasympathetic nervous system.
The efferent limb of the reflex increasing colon motility is mediated by CCK and gastrin.
97
Rectosphincteric reflex?
As rectum fills with faeces, the smooth muscle of the rectum contracts and the internal anal sphincter relaxes
98
Muscle relaxation and contraction process of defecation?
External anal sphincter ( composed of striated muscle and under voluntary control) remains tonically contracted.
External anal sphincter is relaxed voluntarily, the smooth muscle of the rectum contracts and the pressure forces faeces through the anal canal.
99
Vomiting:
Centre where?
Afferent information?
Efferent response?
Vomiting centre in the medulla
```
Afferent information:
• Vestibular system
• Back of throat
• GI tact
• Chemoreceptor trigger zone in the 4th ventricle
```
Efferent response:
• Reverse peristalsis in small intestine
• Relaxation of the stomach and pylorus
• Forced inspiration to increase abdominal pressure
• Relaxation of the lower oesophageal sphincter
• Forceful expulsion of gastric and duodenal contents
100
Change of muscle in the oesophagus?
Upper 1/3: striated muscle as swallowing is voluntary and rapid
Lower 1/3: smooth muscle, involuntary
Middle 1/3: mixed
101
Cricopharyngeal sphincter:
What is it?
Function?
Indentation caused by the normal function of the cricopharyngeal sphincter between the pharynx and the oesophagus
Function:It is to prevent air being sucked into the stomach during inhalation
102
```
Superior/cervical third of oesophagus:
Begins at?
Arterial supply?
Venous drainage?
Nerve supply?
Lymphatics?
```
Begins at C6
Arterial supply from inferior thyroid arteries
Venous drainage to brachiocephalic veins
Nerve supply from branches of the vagus nerves (recurrent laryngeal nerves)
Lymphatics drain to deep cervical nodes
103
```
Middle/thoracic third of oesophagus:
Arterial supply?
Venous drainage?
Nerve supply?
Lymphatics?
```
Arterial supply direct from thoracic aorta and bronchial arteries
Venous drainage to azygos system (systemic)
Nerve supply from the oesophageal plexus (vagus and sympathetic)
Lymphatics drain to tracheobronchial nodes
104
```
Inferior/ abdominal third of oesophagus:
Arterial supply?
Venous drainage?
Nerve supply?
Lymphatics?
```
Arterial supply from left gastric artery
Venous drainage to left gastric veins and therefore to portal vein
Nerve supply from branches of the oesophageal plexus (vagus and sympathetic)
Lymphatics drain to left gastric and coeliac nodes
105
What are the 4 oesophageal constrictions?
1. Upper oesophageal sphincter 17cm
2. Arch of aorta
3. Left main bronchus at 28cm
4. Diaphragm (lower oesophageal sphincter) at 43cm
106
Structures anterior to the oesophagus (5)
```
Trachea
Right pulmonary artery
Left main bronchus
Left atrium
Diaphragm
```
107
Structures posterior to the oesophagus (3)
```
Vertebral bodies (C6 – T12)
Thoracic duct (partly)
Thoracic aorta (inferiorly)
```
108
Name a structure on the RHS and LHS of the oesophagus?
Thoracic aorta lies to the left
| Azygos vein lies to the right
109
What is the epithelium and muscle type of the oesophagus?
It is lined by stratified squamous epithelium (transport) with submucosal mucous glands (lubrication) and has smooth muscle walls
110
```
Abdominal oesophagus:
Where does it enter the abdomen?
Arterial supply?
Venous drainage?
Lymph drainage?
Nervous supply?
```
Where does it enter the abdomen?
It passes through the right crus of diaphragm at T10 (or 7th costal cartilage), but just to the left of the midline
Arterial supply?
Arterial supply is from the left gastric artery (and inferior phrenic)
Venous drainage?
Is to the portal vein
Lymph drainage?
Is to nodes along the left gastric artery and then coeliac nodes
Nervous supply?
By the oesophageal plexus, which is both vagal (p’symp and afferent) and sympathetic
111
What is the cardiac orifice?
The superior opening into the stomach from oesophagus
112
What forms the porto-systemic or portocaval anastomosis
Submucosal veins in the oesophagus form an anastomosis between its middle and lower thirds. The middle third drains to the azygos vein that drains to the SVC (systemic). The lower third drains to the left gastric vein that drains to the portal vein. Therefore this anastomosis is between the portal and systemic circulations i.e. a porto-systemic or portocaval anastomosis
113
Consequence of cirrhotic liver disease
Cirrhotic liver disease raises the portal venous pressure (portal hypertension) and blood escapes via the submucosal veins in the oesophagus and in to the systemic azygos vein. Consequently the veins become dilated and tortuous: oesophageal varices
--> Which may cause fatal haemorrhage
114
How is reflux prevented at the lower end of the oesophagus? 3
No anatomical sphincter, physiological sphincter
Reflux is prevented by a “physiological” cardiac sphincter: 1. Contraction of the right crus of the diaphragm
2. The tonic contraction of the circular layer of smooth muscle in the lower oesophagus
3. The “valvular” effect of the oblique entry of the oesophagus into the stomach, augmented by the oblique muscle layer
Sphincter closure under vagal control
115
What does z-line is oesophagus show?
The transition from stratified squamous (oesophageal) to columnar (gastric) epithelium is visible as the Z-line
116
Which regions does the stomach lie in?
It lies across the epigastric region, but extending to the umbilical and left hypogastric regions
117
Anterior and posterior relations of the stomach
Anteriorly related to: anterior abdominal wall; left costal margin; left pleura and lung (above diaphragm); diaphragm itself; left lobe of the liver
Posteriorly related to: lesser sac; diaphragm; spleen; left suprarenal gland; upper part of left kidney; splenic artery; pancreas; transverse mesocolon; transverse colon
118
What are the 4 parts of the stomach?
Cardia
Fundus
Body
Pyloric part (pyloric Antrum and canal)
119
What happens to the circular muscle in the pyloric region?
Thicken to form the pyloric sphincter that controls the outflow of gastric contents in to the duodenum
120
What are rugae?
Mucosal folds
| aka maganstrasse
121
Change to bolus in stomach?
The stomach receives and stores food and fluid, adds more fluid plus acid and enzymes to create chyme and carry out digestion
122
Blood supply to stomach?
The arteries are all derived from the
branches of the coeliac artery (trunk or axis)
The left gastric artery:
- Arises from the coeliac artery.
- It supplies the lower third of the
oesophagus and the proximal part of the lesser curve and adjacent body of the stomach.
The right gastric artery
- Arises from the hepatic artery at the upper border of the pylorus.
- It supplies the distal part of the lesser curve and adjacent body of the stomach.
The short gastric arteries
- Arise from the splenic artery
- Supply the fundus
The left gastro-epiploic (omental) artery
- Arises from the splenic artery
- Supply the stomach along the proximal part of the greater curvature and adjacent body
The right gastro-epiploic artery
- Arises from the gastroduodenal branch of the hepatic artery;
- Supplies stomach along the distal part of the greater curvature and adjacent body
123
Arteries that supply stomach?
The left gastric artery:
The right gastric artery
The short gastric arteries
The left gastro-epiploic (omental) artery
The right gastro-epiploic artery
The arteries are all derived from the
branches of the coeliac artery (trunk or axis)
124
Where does the gasproduodenal artery lie in relation to the duodenum?
Posterior to the first part
125
Venous drainage of the stomach?
| 4 vessels
The veins all drain into the portal circulation
1 +2. The left and right gastric veins drain directly into the portal vein
3. The right gastro-epiploic vein joins the superior mesenteric vein
4. The short gastric veins and the left gastro-epiploiac veins join the splenic vein
126
What is vagotomy?
Operations done to cut the vagal trunks to:
- Reduce gastric acidity and prevent ulcers
Side effect:
-Motility was also affected causing patients to suffer incredible fullness
So consequently the vagal branches were found and sectioned selectively and highly selectively, after the hepatic branches, and after those going to the pyloric sphincter (nerve of Latarget), so that sphincteric function is maintained
127
What is vagotomy?
Operations done to cut the vagal trunks to:
- Reduce gastric acidity and prevent ulcers
Side effect:
-Motility was also affected causing patients to suffer incredible fullness
So consequently the vagal branches were found and sectioned selectively and highly selectively, after the hepatic branches, and after those going to the pyloric sphincter (nerve of Latarget), so that sphincteric function is maintained
128
Stomach bed:
Formed by?
Superiorly?
Inferiorly?
Formed by the posterior wall of the lesser sac, and retroperitoneal structures between it and the posterior abdominal wall
Superiorly: part of the diaphragm (left crus), the spleen, the left suprarenal gland and upper pole of the left kidney
Inferiorly: body and tail of pancreas, transverse mesocolon, left colic flexure and the splenic artery
129
Stomach bed:
Formed by?
Superiorly?
Inferiorly?
Formed by the posterior wall of the lesser sac, and retroperitoneal structures between it and the posterior abdominal wall
Superiorly: part of the diaphragm (left crus), the spleen, the left suprarenal gland and upper pole of the left kidney
Inferiorly: body and tail of pancreas, transverse mesocolon, left colic flexure and the splenic artery
130
```
Duodenum:
Shape?
Relations?
Position in peritoneum?
Functions?
```
C shaped structure
Adjacent to the head of the pancreas
It is mainly retroperitoneal and receives the openings of the bile and pancreatic ducts
Functions are: continued digestion, especially of fats; and absorption
131
```
Duodenum:
Shape?
Relations?
Position in peritoneum?
Functions?
```
C shaped structure
Adjacent to the head of the pancreas
It is mainly retroperitoneal and receives the openings of the bile and pancreatic ducts
Functions are: continued digestion, especially of fats; and absorption
132
What occurs at the major papilla
Duodenum has 4 parts and receives the bile and pancreatic ducts together at the major papilla
133
1/4 part of the duodenum start?
1st or superior part begins at the pylorus and runs upward, backward and to the right, starting on the transpyloric plane at the level of the 1st lumbar vertebra
134
2/4 part of the duodenum start
| Major papilla?
2nd or descending part runs vertically downward in front of the hilum of the right kidney on the right side of the 2nd and 3rd lumbar vertebrae
About halfway down its medial border, the bile duct and the main pancreatic duct pierce the duodenal wall at the major duodenal papilla
135
Other name for major papilla?
Ampulla of Vater
136
3/4 part of the duodenum start?
3rd or horizontal part runs horizontally to the left on the subcostal plane, passing in front of the vertebral column at L3 and following the lower margin of the head of the pancreas
137
4/4 part of duodenum journey?
4th or ascending part runs upward and to the left to the duodenojejunal flexure at L2
138
35
[]
139
36
[]
140
Duodenum blood supply? Upper/lower halves
The upper half is supplied by:
- Supraduodenal and gastroduodenal branches of the common hepatic artery (Coeliac trunk, foregut)
The gastroduodenal gives anterior and posterior superior pancreaticoduodenal branches
The lower half is supplied by:
- Superior mesenteric artery (midgut) that gives the Inferior pancreaticoduodenal artery, which quickly divides into anterior and posterior branches
141
Duodenum venous drainage?
The superior pancreaticoduodenal vein drains into the portal vein; the
inferior vein joins the superior mesenteric vein
142
Duodenum lymph drainage?
Coeliac and SM nodes
143
Duodenum nerve supply?
The nerves are derived from sympathetic greater (T5 to T9) and lesser splanchnic (T10 and 11) nerves and parasympathetic (vagus) nerves via the coeliac and superior mesenteric plexuses
(Change from foregut to midgut)
144
Nerves that supply foregut?
T5-9
145
Nerves that supply midgut?
T10-11
146
Physical/ innate host defences in the GI tract
* Mouth
* Oesophagus
* Stomach
* Small intestine
* Large intestine
147
4 features of the mouth as a host defence
* Flow of liquids
* Saliva
* Antimicrobials
* Normal microbiota
148
2 features of oesophagus as a host defence
* Flow of liquids
| * Peristalsis
149
3 features of the stomach as a host defence?
Acid pH
Antimicrobial
Mucus
150
7 features of SI as a host defence
* Flow of gut contents
* Peristalsis
* Mucus
* Bile
* Secretory IgA
* Antimicrobial peptides
* Normal bacterial microbiota
151
4 features of large intestine as a host defence
* Normal microbiota
* Peristalsis
* Mucus
* Shedding and replication of epithelium
152
Name the 3 host-bacteria relationships and the host/bacteria attitude
Commensal:
Host =Unaffected
Bacteria =Happy
Symbiotic:
Host = Happy
Bacteria = Happy
```
Parasitic = Unhappy
Bacterium = Happy
```
153
Probiotics:
Name 3?
Action?
Produce what?
E.g.
• Lactobacillus spp.
• Bifidobacterium spp.
• Bacteroides spp
Action: Alters pH but producing lactic acid
154
What are prebiotics?
Non-deigestible food ingredients
| Stimulate growth / activity of gut microbiota
155
Functions of probiotics and probiotics?
```
Development of mucosal barrier
Synthesis of vitamins
Metabolism of bile acids
Production of short-chain fatty acids
Reduction of pH in large bowel
Immune system activation
```
156
Role of gut microbiota (5)
* Prevent colonisation by pathogens
* Excrete useful metabolites
* Ferment unused energy substrates
* Synthesise and excrete vitamins
* Produce hormones
157
A flourishing gut/ecosystem --> Devastation by ______ ---> Left alone --> Prebitiocs, probiotics, ______ ---> Restored ecosystem
A flourishing gut/ecosystem --> Devastation by ANTIBIOTICS ---> Left alone --> Prebitiocs, probiotics, BACTERIOTHERAPY ---> Restored ecosystem
158
Factors Controlling Gut Microflora (7)
* Physiological status
* Underlying disease
* Intestinal secretions
* Intestinal motility
* Immune mechanisms
* Environmental factors
* Use of antibiotics
159
Primary immune organ in the body?
GI tract
GI microbiota has a strong influence on the development of the local and systemic immunity and in the regulation of immune functions
160
Name 4 features associated with pathogen recognition?
1. PAMPs / MAMPs: pathogen / microbe associated molecular patterns
2. TLRs: Toll-like receptors
3. NODs: nucleotide-binding oligomerization
domain-containing proteins
4. NLRs: NOD-like receptors
161
What are the gut microbiota- gut mucosa interactions?
Commensals and pathogens can induce local immune response.
Stimulates release of NK-kB
-->
Transciption of pro-inflammatory genes
--> Secretion of cytokines and chemokine such as TNF and IFN-gamma
NF-κB is a protein complex that controls transcription of DNA, cytokine production and cell survival
162
Diarrhoea:
What is it?
Cause?
Results in?
What is it? Abnormal faecal discharge characterised by frequent and/or fluid stool.
Cause? Result of disease in small intestine
Results in? Involves increased fluid and electrolyte loss
163
Dysentery:
What is it?
Due to?
Associated symptoms?
What is it?
Inflammation disorder of GI tract
Due to:
Disease of large intestine / infection
Associated symptoms:
- Blood and pus in the faeces
- Pain
- Fever
- Abdominal cramps
164
Classification method for stools?
Bristol stool chart
| Type 1-7 (hard small lumps --> entirely liquid)
165
Acquisition of intestinal infection
Ingestion of infected food and water
Ingestion of bacterial toxins
Use of oral antibiotics
166
What are the symptoms of gastroenteritis? 4
Nausea
Vomiting
Diarrhoea
Abdominal discomfort
167
What is enterocolitis?
Inflammation involving the mucosa of both and large intestine
168
Which 4 structures are responsible for secreting into the GI tract?
Salivary glands (in saliva)
Cells of the gastric mucosa (gastric secretion)
Exocrine cells of the pancreas (pancreatic secretion)
Liver (bile)
Addition of fluids, enzymes and mucous to the lumen of the GIT
169
Saliva:
Characteristics?
Factors that increase secretion?
Factors that decrease decrease?
Characteristics:
- High HCO3-
- High K+
- Hypotonic
- Alpha-amylase and lingual lipase
Factors that increase secretion:
- Parasympathetic (primarily)
- Sympathetic
Factors that decrease decrease:
- Sleep
- Dehydration
- Atropine
170
3 features of the structure of the salivary glands
1. Paired
Parotid: Serous cells secreting an aqueous fluid composed of water, ions and enzymes
Sublingual: Mostly mucous cells
Submandibular: Mixed glands containing serous and mucous cells
2. High blood flow
3. Parasympathetic (dominant) and sympathetic supply both stimulate saliva production
171
Compound in mucous responsible for lubrication?
Mucin glycoprotein
172
Role of acinar cells in salivary glands?
Acinar cells produce an initial isotonic saliva composed of water, ions, enzymes and mucus
173
Role of myoepithelial cells in salivary glands
Myoepithelial cells in (and near) the acini are stimulated by neural input to eject saliva
174
Role of ductal cells in salivary glands?
Ductal cells modify the initial saliva by altering electrolyte concentrations
175
What are the 4 methods of salivary modification?
Combined action
– Absorption of Na+ and Cl-
– Secretion of K+ and HCO-3
– Because more NaCl is absorbed than KHCO3 secreted there is net absorption of solute
– Low water permeability of ductal cells means that the final saliva is hypotonic
176
What 4 compounds are secreted by acinar cells?
1. alpha-amylase: Begins the initial digestion of carbohydrates
2. Lingual lipase: Begins the initial digestion of lipids
3. Mucus: lubricant
4. Kallikrein: Enzymatic cleavage of kininogen to bradykinin (potent vasodilator)
177
What is the neural regulation of salivary secretion?
* Salivary secretion is exclusively under neural control by the ANS (no hormonal regulation)
* Salivary secretion is increased by both the parasympathetic and sympathetic nervous system
* Neural stimulation results in an increased saliva production, HCO-3 production, enzyme secretion and myoepithelial cell contraction
178
Difference between PS and sympathetic innervation on salivary secretion?
PS: Produce fluid/ protein in saliva by binding to muscarinic receptor
Symp: Produces mainly protein in saliva by binding to beta adrenal receptor
179
What are the 4 components of gastric juice?
1. HCl: For protein digestion
2. Pepsinogen: for protein digestion]
3. Intrinsic factor: carries Vit B12 to ileum for absorption
4. Mucus: Proteins the gastric mucosa and lubricates food
180
Gastric secretions:
Characteristics?
Factors that increase?
Factors that decrease?
Characteristics:
HCl
Pepsinogen
Intrinsic factor
```
Factors that increase:
Gastrin
ACh
Histamine
Parasympathetic
```
```
Factors that decrease:
H+ in stomach
Chyme in duodenum
Somatostatin
Atropine
Cimetidine
Omeprazole
```
181
3 secretors gastric cells
Parietal/ oxyntric cells (found in stomach body)
Chief/peptic cells (found in stomach body)
G cells (found in stomach Antrum )
182
Structure of an oxyntric/gastric gland?
| Compounds secreted by cells?
Surface epithelium
Mucous neck cells: Secrete mucous
Oxyntric/ parietal cells: Secrete HCl and intrinsic factor
Peptic/chief cells: Secrete pepsinogen
183
What cells secrete HCl?
| What is the consequence of HCl secretion?
Parietal cells secrete HCl which acidifies the gastric contents to pH 1 – 2.
Secretes H+ (via ATPase protein) and Cl-, to form HCl
Low gastric pH converts inactive pepsinogen to pepsin (active form)
Pepsin is a protease which initiates protein digestion
184
How is the H+ ion produced in parietal cells?
Carbonic anhydrase catalyses the combination of metabolic CO2 and H2O
CO2 + H2O --(carbonic anhydrase)--> H2CO3 --> H+ and HCO3-
185
What are the different processes that occur at the apical and basolateral surfaces of parietal cells to secrete HCl
Basolateral surface:
HCO-3 (into blood) is exchanged for Cl- (into cell) via the chloride-bicarbonate exchanger (alkaline tide)
Eventually HCO-3 that has been put into blood is secreted back into the GI tract in pancreatic secretions
Apical surface:
H+ is secreted into the lumen via the H+-K+ ATPase
Cl- follows by diffusion through an apical channel
186
What are the two phases of gastric HCl release?
Cephalic phase
- 30% of secretion
- Smell, taste, chewing, swallowing, conditioned reflex in anticipation of food
- Direct stimulation of the parietal cells by the vagus
- Indirect stimulation of the parietal cells by gastrin
Gastric phase
-60% of secretion
-Distension of the stomach and the presence of breakdown products of proteins, amino acids and small peptides in the stomach
Amino acids and small peptides on G cells stimulates gastrin release
Intestinal phase
- 10% of secretion
- Presence of breakdown products of proteins in the duodenum
187
What does vagal GRP stimulate?
Vagal gastrin releasing peptide (GRP) stimulates gastrin
| release from G cells. Gastrin hormone enters the circulation and stimulates parietal cells to release HCl
188
Distension causes what 3 things?
– Direct vagal stimulation of parietal cells
– Indirect stimulation via gastrin
– Local reflexes in the antrum that stimulate gastrin
release
189
What are the direct and indirect methods of regulation of HCl secretion?
Direct vagal pathway:
Vagal release of ACh activates parietal cells
Indirect vagal pathway:
Vagal stimulated released of gastrin into circulation from G cells (by GRP neuropeptide transmitter)
190
What cells secrete pepsinogen?
| Stimulation of secretion?
* Secreted by chief and mucous cells in the oxyntic glands in response to vagal stimulation
* H+ triggers local reflexes which stimulate chief cells to secrete pepsinogen
191
Intrinsic factor secretion:
What is intrinsic factor?
Absence causes...
Relevance in gastrectomy patients?
What is it?
• Mucoprotein released from parietal cells required for Vitamin B12 absorption in the ileum
• Only essential secretion of the stomach
Absence causes..
• Lack of intrinsic factor causes pernicious anaemia
• Following gastrectomy, patients receive injections of Vitamin B12 to bypass the absorption defect
192
What is Zollinger-ellision syndrome?
Endocrine tumour known as gastrinoma (gastrin secreting tumour)
Usually non-B cell of the pancreas
Leads to high circulating levels of gastrin, leading to high H+ secretion by parietal cells --> Hypertrophy of the gastric mucosa --> duodenal ulcers + acidification of the intestinal lumen
193
Ileum --> ________ --> Anus
```
Ileum
-->
Large intestine: caecum plus appendix; ascending colon; transverse colon; descending colon; sigmoid colon;
-->
Rectum and anal canal
-->
Anus
```
194
The jejunum begins at the _______ flexure, and the ileum ends at the _______ junction in the right iliac fossa. There is a ______ change from jejunum to ileum
The jejunum begins at the duodenojejunal flexure, and the ileum ends at the ileocaecal junction in the right iliac fossa. There is a gradual change from jejunum to ileum
195
Difference in position between the jejunum and ileum?
The jejunum lies in the upper left abdomen, while the ileum tends to be lower right and also in the pelvis
196
Difference between jejunum and ileum
Jejunum:
- Wider bored
- Thicker walled : because the permanent infoldings of the submucosa, the plicae circulares, are larger, more numerous, and more closely set in the jejunum
- Redder
197
Difference between jejunum and ileum
Jejunum:
- Wider bored
- Thicker walled : because the permanent infoldings of the submucosa, the plicae circulares, are larger, more numerous, and more closely set in the jejunum
- Redder
Mesentery of jejunum:
The mesenteric vessels form only one or two arcades, with long and less frequent branches passing to the intestinal wall
The fat is deposited near the root and is less obvious near the intestinal wall
Mesentery of ileum:
The ileum receives numerous short terminal vessels that arise from a series of three or four or even more arcades
The fat is deposited throughout so that it extends from the root to the intestinal wall
Peyer's patches in mucous membrane of lower ileum along anti-mesenteric border
198
What are Peyer's patches?
Aggregations of lymphoid tissue (Peyer's patches) are present in the mucous membrane of the lower ileum along the antimesenteric border;
199
What are Peyer's patches?
Aggregations of lymphoid tissue (Peyer's patches) are present in the mucous membrane of the lower ileum along the antimesenteric border;
200
What is the ileocaecal valve?
Structure
Function?
A rudimentary structure, the ileocaecal valve consists of two horizontal folds of mucous membrane that project around the orifice of the ileum, situated at the junction of the small intestine (ileum) and the large
intestine
Its function is to limit the reflux of colonic contents into the ileum and possibly control the flow of ileal contents into the caecum
201
Mid gut derived structure send referred pain to...
Peri-umbilical area (T10)
202
Ileum and jejunum: Blood (arteries and venous), lymph and nerve supply?
Jejunal and ileal arteries from the Superior Mesenteric Artery and its ileocolic branch
The veins correspond to the branches of the SMA and drain into the superior mesenteric vein, which forms the portal vein
Lymph Drainage is to superior mesenteric nodes, which are situated around the origin of the SMA
Nerve Supply is derived from the sympathetic, lesser splanchnic nerve T10 and 11, and parasympathetic (vagus) nerves via the superior mesenteric plexus
203
What forms a sequence of vascular, anastomotic arcades in the mesentery?
SMA
204
Intestinal lymph drainage via the mesentery
There is a lacteal in the centre of each villus for the absorption of digested fats and lipids (chyle).
The chyle passes from the lacteals into mesenteric lymph channels that DO NOT pass through lymph nodes but converge on the cisterna chyli and passes through the diaphragm as the thoracic duct (the absorbed LIPID molecules are TOO BIG for the lymph node “filters”)
The intestinal wall is packed with lymphocytes, in the ileum these aggregate as Peyer’s patches.
Lymph absorbed from the intestinal wall again passes into mesenteric lymph channels, but these FILTER through the mesenteric nodes
Afferents from the mesenteric nodes converge on nodes at the root of the SMA
Afferents from the nodes on the SMA pass to the cisterna chyli
205
Meckels Diverticulum:
How is it formed?
Remnant of?
Side effects?
How is it formed?
As intestinal tract communicates with yolk sac, can leave behind a Meckel's Diverticulum
Remnant of?
The Vitello-intestinal duct
Side effects?
May ulcerate causing signs and symptoms similar to appendicitis
206
Structures that make up colon
Consists of the caecum, ascending colon, hepatic (right) flexure, transverse colon, splenic (left) flexure, descending and sigmoid colon, rectum and finally anal canal
207
Function of colon?
Absorbs fluid and salts, dries out the chyme to form faeces
208
Peritoneum relations of colon?
The ascending and descending parts are retroperitoneal
| The transverse and sigmoid colon are on a mesentery, i.e. intraperitoneal
209
3 distinctive external features of colon
1. Possesses tags of fat - omental appendices (appendices epiploicae)
2. Possesses 3 taeniae coli – condensations of the longitudinal muscle layer
3. Possesses (sacculations) haustra of the colon
210
3 distrinctive internal features of the colon
1. Lacks plicae circularis
2. Lacks villi
3. Lacks peyers patches
211
Caecum
Caecum, mesentery?
Relevance of peritoneal recesses around it?
How to find appendix in surgery?
Caecum not on a mesentry
Variable peritoneal recesses may form adjacent to caecum, appendix may be found in any of these recesses
The 3 taeniae coli converge in the caecum at the root of the appendix and may be a guide to its location during surgery
212
Appendix:
What is it?
Position?
What is it? The appendix is a narrow blind ended tube hanging from the caecum
Its submucosa is packed full of lymphoid tissue
Position?
Root of appendix at McBurney’s point – 1/3 up from ASIS to umbilicus
It is suspended on a short, but highly variable meso-appendix that transmits the appendicular vessels
213
Possibile structures affected by appendicitis?
The appendicular artery is close and parallel to the appendix distally, therefore it may be affected by an inflamed appendix and become obstructed causing gangrene and rupture of the appendix
214
Early appendicitis refers pain to....
The peri-umbilical region; if the appendicular artery travels with nerves from T10/11
As time passes when the parietal peritoneum is involved, the overlying skin is affected
215
Blood supply to the caecum and appendix?
All derived from the ileocolic artery from the SMA
- Anterior caecal artery
- Posterior caecal artery
- Appendicular artery (from posterior caecal)
[Hence lymph drainage is to nodes on the SMA]
216
Which section of the colon is mobile?
The sigmoid colon is mobile on a fan-shaped mesentery and hangs down into the pelvic cavity in the form of a loop
It may rotate upon itself: sigmoid volvulus.
217
What colonic structure can present as left sided appendicitis
Colonic diverticulae may become obstructed and mimic left sided “appendicitis”
218
Colon blood supply
SMA branches:
- Ileocolic to caecum
- Right Colic to ascending colon
- Middle colic to hepatic flexure and 2/3 transverse colon
IMA branches:
- Left colic to 1/3 transverse colon, splenic flexure, descending colon
- Sigmoid to sigmoid
These vessels cross the ureters and gonadal vessels
[Equivalent veins run with the arteries and drain to the portal vein; lymph drainage is to nodes on the SMA and IMA]
219
```
IMA:
Supplies?
Carries which nerves?
Forms which anastomosis?
Forms collateral in the event of what?
```
The inferior mesenteric artery (IMA) supplies the hindgut i.e. last 1/3 of transverse colon to rectum and proximal anal canal
Carries sympathetic nerves derived from T12 and parasympathetics from S 2, 3, 4 (NOT vagus) .
It forms an important anastomosis with the SMA the Marginal Artery (of Drummond)
May form a collateral circulation should the IMA become obstructed
220
Referred pain, which nerves supply which ___guts? Referred pain of each region?
Autonomic nerves run with the 3 arteries:
1. Coeliac trunk to foregut
- Lower oesophagus, stomach, duodenum
- Refer to upper abdomen (T7 – 9)
2. Superior mesenteric to midgut
- Duodenum to 2/3 transverse colon
- Refer to peri-umbilical region (T10/11)
3. Inferior mesenteric to hindgut
- Refer to suprapubic region (T12)
221
Pancreatic secretion:
Characterics?
Factors that increase secretion?
Characteristics:
High HCO-3 (isotonic)
Pancreatic lipase, amylase and proteases
Factors that increase secretion:
Secretin
Cholecystokinin (CCK) (potentiates secretin)
Parasympathetic supply
222
What does the pancreas secrete?
into where?
Why?
Fluid into the duodenum
Composition: Aqueous, enzymes, high HCO-3
HCO-3: Neutralises stomach H+
Enzymes: Digest carbohydrates, proteins and lipids
223
Pancreas:
Innervation?
Enzyme storage?
Innervation:
PS= From vagus stimulates secretion
Symp= Inhibits secretion
Pancreatic enzymes are stored in condensed zymogen granules until release
224
What is the process of formation and release of pancreatic secretions?
Composition of pancreatic fluid?
Modification of ductal cells?
Enzymes released from acinar cells, passes centroacinar cells then follow out via ductal cells as an isotonic pancreatic secretion.
Pancreatic fluid is an isotonic fluid containing Na+, K+Cl- and HCO-3
Ductal cells concentrate HCO-3 in fluid
225
Enzymatic component of pancreatic secretions?
Pancreatic amylase and lipase are secreted as active enzymes
| Pancreatic proteases are secreted in an inactive form and activated in duodenum (enterokinase)
226
Regulation of pancreatic secretion, 3 phases?
Cephalic phase initiated by taste, smell and conditioning mediated by the vagus nerve ( mainly enzymatic secretion)
Gastric phase initiated by distension of the stomach and mediated by the vagus nerve ( mainly enzymatic secretion)
Intestinal phase accounts for 80% of pancreatic secretion and both enzymatic and aqueous secretions are stimulated
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How are acinar cells regulated?
Duodenal I cells secrete CCK in response to the presence of amino acids, small peptides and fatty acids in the intestinal lumen.
Vagal release of ACh potentiates CCK action
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How is ductal cell secretion regulated?
Ductal cells secrete Na+, K+Cl- and HCO-3
1. Arrival of acidic chyme in the duodenum triggers secretin release
2. S cells of duodenum secrete SECRETIN, stimulating HCO-3 release from ductal cells
ACh and CCK potentiate secretin action.
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Bile secretion:
Function?
Produced/stored?
Composition?
Bile is essential for the digestion and absorption of lipids (water insoluble)
Produced and secreted by the liver and stored in the gall bladder
Mixture of bile salts, bile pigments and cholesterol
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Function of bile salts?
Bile salts emulsify lipids to prepare them for digestion and solubilise the products of digestion into ‘packets’ called micelles
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3 functions of the gallbladder
1. Reservoir for bile
Stores the bile which is continuously produced by the hepatocytes and flows to the gallbladder through the bile ducts
2. Concentration of bile
Epithelial cells lining the gallbladder absorb ions and water isosmotically
3. Ejection of bile
Begin 30 minutes after a meal. The major stimulus for ejection is the release of cholecystokinin from the I cells in the duodenum and jejunum.
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The IMA ends as the ____ ___ artery supplying the rectum and anal canal
The IMA ends as the superior rectal artery supplying the rectum and anal canal
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What are the different layers of the GIT? (Inner to outer)
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Lumen
Epithelium
Muscularis mucosae
Submucosa
Inner circular muscle
Auerbach's myenteric plexus of ganglia and nerves
Outer longitudinal muscle
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What is hirchsprung disease?
Lack of normal development of the colonic innervation leads to a constricted, aganglonic segment proximally
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Rectum is ___peritoneal
Rectum is retroperitoneal
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What is cholecystokinin?
| When/why/where is it secreted
A 33 amino acids peptide hormone related to gastrin
Secreted from the I cells of the duodenal and jejunal mucosa in response to the presence of monoglycerides, fatty acids, small peptides and amino acids
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5 hormonal action of cholecystokinin
1. Contraction of the gall bladder and relaxation of the
sphincter of Oddi to eject bile (emulsification and solubilisation of dietary fat)
2. Secretion of pancreatic enzymes (both lipases and proteases)
3. Secretion of pancreatic HCO3
4. Growth of exocrine pancreas and gall bladder
5. Inhibition of gastric emptying
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Control of the biliary system:
1. ______ synthesise and secrete the constituents of bile (bile salts, cholesterol, phospholipids, bile pigments, ions and water)
2. Bile flows from liver in bile ____ and is stored and _____ in the gall bladder
3. Chyme in the small intestine triggers ___release:
- stimulates gall bladder _____
- stimulates relaxation of the Sphincter of ____
4. When lipid absorption is complete bile salts are _____ to the liver by the enterohepatic ___ circulation
5. Bile salts are extracted from the portal blood by _____ (20% loss per day)
1. Hepatocytes synthesise and secrete the constituents of bile
(bile salts, cholesterol, phospholipids, bile pigments, ions and water)
2. Bile flows from liver in bile ducts and is stored and concentrated in the gall bladder
3. Chyme in the small intestine triggers CCK release stimulates gall bladder contraction
stimulates relaxation of the Sphincter of Oddi
4. When lipid absorption is complete bile salts are recirculated to the liver by the enterohepatic portal circulation
5. Bile salts are extracted from the portal blood by hepatocytes (20% loss per day)
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What is an emulsion?
Lipid coated in bile salts
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What are mixed micelles?
| Structure?
Products of lipid digestion (cholesterol, monoglycerides, lysolecithin and free fatty acids) and solubilised in mixed micelles.
Structure:
-The core contains the products of lipid digestion
-Surface coating of bile salts which are amphipathic
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What are the two pathways of absorption?
Cellular and paracellular
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Structure of the intestinal mucosa:
- Arrangement of SI surface?
- Structure of villi?
- Apical surface of epithelial cells covered by?
Surface of the small intestine isarranged in circular folds of Keckring
Villi project from the folds.
Surface of the villi are covered with epithelial cells (enterocytes) with mucus secreting cells (goblet cells)
Apical surface of epithelial cells covered by microvilli – brush border
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Carbohydrate:
Products?
Site of digestion?
Mechanism of digestion?
Limitation?
Begins in?
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Products:
- Glucose
- Galactose
- Fructose
Site: SI
Mechanism:
Na+-dependant cotransport Na+-dependant cotransport
Facilitated diffusion\
Limitation: Only monosaccharides can be absorbed
Begins with salivary -amylase (minor role)
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Absorption of carbohydrate, 2 forms. Secondary active transport and facilitated diffusion. Explain
Secondary active transport
– SGLT 1 (sodium dependent glucose transporter 1) located on the apical membrane transports glucose and galactose
Facilitated diffusion
– GLUT 5 (glucose transporter 5) transports fructose across the apical membrane
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Protein digestion:
Begins in?
Completed in? How?
Begins in the stomach with pepsin
Completed in the small intestine with pancreatic and brush-border proteases
– Endopeptidases hydrolyse the interior peptide bonds of proteins
– Exopeptidases hydrolyse one amino acid at a time from
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Two proteins int eh SI that digest proteins?
1. ENDOPEPTIDASES hydrolyse the interior peptide bonds of proteins
2. EXOPEPTIDASES hydrolyse one amino acid at a time from
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Process of activation of protein digesting proteins
Pancreatic proteases secreted as inactive precursors (E.g. Trypsinogen)
Initial step- activation of trypsinogen to the active form, trypsin, by the brush-border enzyme enterokinase
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This trypsin catalyses the conversion of the other inactive precursors to active enzymes
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Understand the 4 COMA definitions in the UK Dietary Reference Values.
Safe intake
Estimated Average Requirement (EAR)
Reference Nutrient Intake (RNI
Lower Reference Nutrient Intake (LRNI)
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What is an RNI?
Reference Nutrient Intake (RNI)
The RNI is the amount of a nutrient that is enough to ensure that the needs of nearly all the group (97.5%) are being met. By definition, many within the group will need less.
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Be aware that the EAR is used in particular for energy. What is EAR?
Estimated Average Requirement
This is an estimate of the average requirement for energy or a nutrient. For a group of people receiving adequate amounts, the range of intakes will vary around the EAR.
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What is the LRNI?
Lower Reference Nutrient Intake.
The amount of a nutrient that is enough for only the small number of people who have low requirements (2.5%). The majority need more.
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What is safe intake?
This is used where there is insufficient evidence to set an EAR, RNI or LRNI. The safe intake is the amount judged to be a level or range of intake at which there is no risk of deficiency and is below the level where there is a risk of undesirable effects. There is no evidence that intakes above this level have any benefits - and in some instances they could have toxic effects.
