Week 2 Flashcards
What 4 factors need to be considered when undertaking a medical elective in resource poor countries?
- Stay within your competence
- Maintain ethical standards
- Develop “cultural competence” (Bowman, 2011)
- Minimise burden on host country & healthcare system
Who is classed as a child and young person?
Under 18 in England, Wales and NI
Under 16 in Scotland
Children = People who aren’t mature enough to make important decisions for themselves
When a child lacks capacity, who makes the decision?
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
As well as clinical best interest, what else should be considered?
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.
Name 2 cases in which there was conflict due to doctors and parents disagreeing?
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
What does “Gillick Competent” mean?
A young person under 16 with capacity to make any relevant decision
How is competence determined?
Understand, retain, use/weight this information and communicate decision
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?
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
Outline the Hannah Jones as a mature minor case?
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)
What are the laws on living children organ donors?
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
What are the euthanasia laws for children in Europe?
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
What are the ethical issues surrounded children and clinical research?
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
What is the eu regulation regarding generics and bioavailability?
Generics must have a bioavailability of 80-125% compared to the reference product (EU reg.)
What is generic substitution?
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.
What is therapeutic substitution?
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
Name the advantages and disadvantages of drug administration via oral route?
Advantages – Cheap – Safe – Convenient Disadvantages – Patient compliance – Variation in bioavailability of drug
Particle size and formation, what is contained in a drug capsule?
Drug Excipients Binding agents Lubricants Coatings
List the advantages of the different forms of oral route: Buccal / sublingual mucosa Gastric mucosa Small intestine Large intestine / colon Rectal mucosa
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
4 ways small molecules cross cell membranes
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
What is the physicochemical factor affecting drug absorption?
Drug ionisation
What is the henderson-hasselblach equation for a weak base?
pKa - pH = Log10 [BH+]/[B]
ionised on top
What is the henderson-hasselblach equation for a weak acid?
pKa - pH = Log10 [AH]/[A-]
note ionised on bottom
weak acid are more likely to be absorbed by SI than weak bases
Weak acid are ____likely to be absorbed by SI than weak bases
weak acid are more likely to be absorbed by SI than weak bases
Effect of food on gastric emptying?
Slows the rate
Effect of decreased absorption on drug absorption
Intestinal motility
Interactions with food, acids
Presystemic metabolism
Effect of delayed absorption on drug absorption
Gastric emptying
Clinically important
Cmas may decrease
Increased absorption effect on drug absorption
Poorly water soluble drugs
increased solubilisation
Decreased pre systemic metabolism
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
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
Factors that affect oral absorption?
- Particle size and formulation
- GI motility
3, First pass metabolism
– First pass metabolism by gut wall or hepatic enzymes - Physicochemical factors
– Direct drug interactions, dietary factors, varying pH - Splanchnic blood flow
– Increased flow increases drug absorption - Efflux pumps
– P-glycoprotein
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
What determines the rate of onset when using parenteral routes?
Extent of capillary perfusion
Drug vehicle
Affected by factors that alter perfusion
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
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
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)
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
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
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)
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
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
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
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
How does an obstructive annular pancreas form?
In embryological developement of the foregut if the ventral pancreas may form as 2 lobes
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
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
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
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
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
Greater omentum overlies which structures?
Transverse colon and intestine
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
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
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
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
Name 3 conditions that occur during failure of recanalisation of GI tract?
Gastroschisis
Omphalocele
Umbilical hernia
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
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
What causes an imperforate anus?
- The common origin of the anal canal and the urogenital organs means that fistulae between them may
- Also the anal membrane may not break down
Both causing an imperforate anus
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)
Define the term psychosomatic disorder
Psychosomatic disorders are disorders where emotional or psychological factors can impact on the symptoms
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
What is IBS?
Irritable bowel syndrome a common digestive condition
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
4 impacts of IBS on patients
- work?
- visits to health professionals
- Health Related Quality of Life (HRQoL)
- psychological health
IBS, causes?
- psychological disorders
- hyper-reactivity in the brain-gut interface
- infection
- food intolerance
- abnormal muscle contraction • serotonin receptors
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.
IBS management, 4 main approaches?
- Diet/ lifestyle (physical activity) changes approach
- Food diary: Monitor food intolerances, encourage healthy diet
- Assess activity levels - Drug treatments approach
- Treat the symptoms - Psychological approaches
- After 12 months
- Cognitive behavioural therapy
- Hypotherapy
- Psycholoical therapy - Complementary therapies approach
- Nutraceuticals
- Chinese herbal medicine
- Probiotics
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)
Outline the diet/lifestyles approach to treating IBS?
- Diet/ lifestyle (physical activity) changes approach
- Food diary: Monitor food intolerances, encourage healthy diet
- Assess activity levels
Outline the drug treatments approach to treating IBS?
- 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)
Outline the psychological approach to treating IBS?
- Psychological approaches
- After 12 months
- Cognitive behavioural therapy
- Hypotherapy
- Psycholoical therapy
Outline the complementary therapies approach to treating IBS?
- Complementary therapies approach
- Nutraceuticals
- Chinese herbal medicine
- Probiotics
What is are the major functions of gastric motility? (3)
- Allows stomach to act as a reservoir for the large volume of food ingested at a single meal
- Breaks food into smaller particles and mixes with gastric secretions
- Empties gastric contents into duodenum at controlled rate
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
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
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
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
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.
What is the function of retropulsion in the stomach?
Propels gastric contents back for further mixing in the stomach
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
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
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
Physical factors affecting gastric emptying? 3
- Liquids empty more rapidly than solids
- Isotonic fluids empty more rapidly than hypo- or hypertonic fluids
- Solids must be reduced to particles < 1 mm3 or less. Retropulsion continues until this is achieved
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
3 functions of the motility of the small intestine
- Mixes chyme with digestive enzymes and pancreatic secretions
- Exposes nutrients to the intestinal mucosa for absorption
- Propels unabsorbed chyme into large intestine
Parasympathetic innervation of SI:
Nerve?
Action?
Neurotransmitter?
Nerve: Vagus
Action: Increases contraction
NT: ACh and motilin
Sympathetic innervation of SI:
Nerve?
Action?
Neurotransmitter?
Nerve: Coeliac and superior mesenteric ganglia
Action: Decreases contraction
NT: Noradrenaline
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
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
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
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]
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)
Mass movements in the colon due to..
Gastrocolin and duodenocolic reflexes
Two nerves in inguinal canal
Ilio-inguinal nerve
Genito-femoral nerve
Deep inguinal ring at…
Mid point of inguinal ligament
Femoral pulse felt at….
mid inguinal point
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.
Rectosphincteric reflex?
As rectum fills with faeces, the smooth muscle of the rectum contracts and the internal anal sphincter relaxes
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.
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
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
