Case 11- Physiology and SPA Flashcards
Layers of the Oesophagus
- Mucosa-stratified squamous epithelium
- Submucosa-mucous glands
- Muscular layer-containing inner circular and outer longitudinal muscle fibres
- Serosal layer
- Submucosal plexus (Meissner’s)- within the submucosa it controls secretion, absorption and local muscle movement
- Myenteric plexus (Auerbach’s)- between the circular and longitudinal muscle layers, controls the tone of the gut.
How food moves down the Oesophagus
Once we have chewed our food it moves into the pharynx, causing distention of the pharynx. The epiglottis and glottis close so food doesn’t enter the respiratory tract. The nasopharynx is closed to stop reflux. When we swallow a signal is generated in the brainstem via Vagal nerves. This causes the upper oesophageal sphincter to open so food can move into the oesophagus. There is a wave of relaxation followed by contraction of circular muscles behind the food to squeeze the bolus along, this is peristalsis.
Oesophagus- Peristalsis is triggered by
- Primary peristalsis- swallowing reflex
* Secondary peristalsis- distension of the oesophagus due to the food bolus
Neuronal control in the upper third of the Oesophagus
Contains striated muscle.
Primary Peristalsis- Sequential firing from the Nucleus ambigus (NA) within the Medulla activates the lower motor fibres of the Vagus nerve. This generates timed contraction of the striated muscle allowing peristalsis to occur.
Secondary peristalsis- distension of the oesophagus is detected by the CNS via the afferent vagus nerves. This generates sequential firing to cause muscle contraction.
Neuronal control in the lower third of the oesophagus
Contains smooth muscle. Control of smooth muscle contraction is via the dorsal motor nucleus (DMN) in the medulla. Primary peristalsis is controlled by vagal nerves via the enteric nervous system. Secondary peristalsis is locally controlled
Neuronal control in the lower third of the oesophagus- Excitatory pathway
Primary peristalsis- preganglionic motor nerves originate from the rostral part of the DMN synapse in the myenteric plexus. The activation of the postganglionic fibres cause a release of acetylcholine and substance P. This causes contraction of the smooth muscle behind the bolus.
Neuronal control in the lower third of the oesophagus- Inhibitory pathway
Primary peristalsis- preganglionic motor nerves originate from the caudal part of the DMN synapse in the myenteric plexus. The activation of the postganglionic fibres cause a release of nitric oxide, vasoactive intestinal peptide and ATP. This causes a relaxation of the smooth muscle in front of the bolus.
The lower third of the Oesophagus- Secondary Peristalsis
The submucosal plexus between the mucosa and the inner circular muscle layer senses the distension of the oesophagus. It then forms a connection with the myenteric plexus motor fibres to generate smooth muscle contraction. The lining of the oesophagus at the bottom contains mechanoreceptors which sense stretch. This then signals to the enteric nervous system which triggers an enteric nervous system response.
Why is muscle contraction controlled in the Oesophagus
Behind the trigger there will be contraction due to excitatory response. In front of the trigger there will be relaxation due to an inhibitory response.
The fundus and proximal bodies of the stomach
They act as reservoirs. Two major types of motility occur here: receptive relaxation and gastric accommodation.
Fundus and proximal bodies of the stomach- Receptive relaxation
Receptive relaxation in anticipation of food- controlled by the Vago-vagal reflex. The lower oesophageal sphincter and proximal stomach relax in anticipation of contents.
Fundus and proximal bodies of the stomach- Gastric accomodation
Gastric accommodation- mechanoreceptors sense the stretch in the wall of the stomach when food enters. This causes relaxation of the stomach. It is controlled by the ENS with vagal involvement. If there was no relaxation there would be an increase in intra-gastric pressure putting a greater strain on the sphincters, potentially resulting in reflux. So gastric accommodation causes no change in intra-gastric pressure.
Roles of the distal body and antrum
Has roles in mixing and emptying
Mechanism of action of the distal body and antrum
- Propulsion- peristaltic contractions which move food towards the pyloric sphincter and antrum. There will be occlusion of the pylorus.
- Grinding- the antrum is thick and muscular and crushes and grinds the food. Only particles below 2mm in diameter pass through the pylorus.
- Retropulsion- any larger particles are moved into the body to break them down.
Stomach- intrinsic pacemaker
The interstitial cells of Cajal have an intrinsic pacemaker function generating a membrane potential. This is a sub threshold so requires a further stimuli to generate muscle contractions. This can be Ach and gastrin (excitatory). Or it can be inhibited by NO, VIP and ATP. It is the origin of phasic contractions in the greater curvature of the corpus.
Stomach= gastro-gastro reflexes
Via the enteric nervous system. Distension of the reservoir stimulates antral contractions in anticipation of churning up the food. When the antrum is distended relaxation of the reservoir is required to accommodate the food that will be pushed back in the area to be broken down further. Distension of the antrum leads to prolonged relaxation of the reservoir.
Controls of gastric emptying- Intestinal break
By delaying gastric emptying you give the intestine time to deal with the food that is already there
Control of gastric emptying- stomach contents
Emptying is inhibited by stomach contents (i.e. HCl, amino acids and long chain fatty acids) entering the small intestine. Endocrine cells sense the contents of the gut and release hormones to control their emptying. The hormones are Cholecystokinin (CCK), glucagon-like peptide (GLP-1) and peptide YY.
Control of gastric emptying= Entero-gastric neural reflexes
Receptors in the wall of the duodenum detect the contents of the duodenum, this is sent though afferent fibres to the enteric NS. Vagus nerves then control gastric emptying.
Gastric emptying- Secretin
Low pH causes S cells to release secretin causing bicarbonate secretion. This reduces acid production in the stomach and decreases gastric emptying. The duodenal chemoreceptors also cause more secretin to be released which decrease gastric emptying. The acid in the lumen also reduces gastrin production, inhibiting gastric motility.
Gastric emptying- CCK
I cells produce CCK in response to fat, this decreases gastric emptying. The I cells are a type of duodenal chemoreceptor.
Gastric emptying- Enteric NS
The enteric NS acts to reduce gastric emptying, it does this through contraction of sphincters.
Gastric emptying- Hypertonicity
Hypertonicity is detected by the duodenal chemoreceptors an unidentified hormone is then released to decrease gastric emptying. The Hypotonicity signal is also sent via chemoreceptor afferents to the intramural intrinsic which directly decreases gastric emptying and through the CNS. The CNS increases sympathetic activity and decreases parasympathetic activity in order to decrease gastric emptying.
Vomiting (emesis)
The forceful expulsion of gastrointestinal contents through the mouth. There is contraction of the intercostal muscles generating an increased intrathoracic pressure which squeezes on the stomach. There is no contraction of the stomach muscle itself.
Retching (dry heave)
Chyme moves into the oesophagus due to relaxation of the distal oesophagus but this is followed by immediate backflow. Contraction of the proximal oesophagus stops expulsion. The backflow is due to secondary peristalsis.
What part of the brain causes vomiting
The Medulla Oblongata in an area called the vomiting centre. Sends signals to the respiratory, abdominal and oesophageal muscles and the oesophageal sphincter generating emesis
The receptors which stimulate vomiting
- Higher brain centres respond to stress, severe pain or if you see/smell a certain trigger.
- The Chemical trigger zone is outside the blood brain barrier and is able to detect toxins in the blood and induce vomiting to clear them i.e. morphine.
- Labyrinthine receptors in the ear- the body interprets vertigo as being due to toxin intoxication. This is why people experience motion sickness.
- Touch receptors in the throat- gag reflex.
- Mechanoreceptors and chemoreceptors in the stomach respond to stretch and cytotoxic substances
Mechanism of vomiting
1) Retrograde contraction in the jejunum
2) Chyme moves from the proximal small intestine to the relaxed stomach through the open pylorus, causes nausea and increases saliva
3) Rhythmic respiratory movements against the closed glottis produce negative oscillations in the intrathoracic pressure.
4) This produces retching and the epiglottis and soft palate close.
5) The abdominal muscles and diaphragm contract to increase the intra-abdominal pressure. Squeezing the stomach and forcing its contents out of the mouth, there is opening of the oesophageal sphincters and pyloric contraction.
The micro skills involved in giving a good explanation
1) Giving the right types of information
2) Giving the right amount of information
3) Achieve accurate recall and understanding
Giving the right types of information
Assess starting point (what do they already know?), what they want to know and what other information may be helpful. What information do they need to know?
Giving the right amount of information
Ask how much they want, check back on understanding before proceeding. Give the information in small chunks and use their response as a guide. Leave space for the patient to contribute.
Achieve accurate recall and understanding
Clear language, repeat and summarise, signpost and organise the explanation. You can also check and clarify understanding and use visual methods. At the end of the conversation you can get the patient to recap their understanding.
Types of highlighting
Categorisation is when the doctor states which categories of information are going to be discussed, then relaying the information in these categories. Labelling is when key messages are highlighted, i.e. this is the most important thing I have to tell you.
The benefits of a good explanation
- Helps create a good doctor patient relationship.
- The skill of giving information has often been neglected.
- Reduces anxiety and stress
- Greater patient satisfaction
- Greater concordance with treatment- reducing costs
- Helps achieve a shared understanding and includes the patient in decision making
Challenges involved in giving explanations
- Patients recall less then what is told.
- Patients don’t always understand the information given.
- Patients remember information they find more significant
- Patients remember what they are told first
- The amount and type of information given was the most important predictor for patient understanding
Why we offer medical explanations
You want to provide the correct amount and type of information, tailored to the patients needs. In order to aid accurate recall and understanding. To achieve a shared understanding and involve the patient in shared decision making. Which will help in being patient centred and building the relationship and ultimately to aid concordance.
Problems doctors often make when giving explanations
Problems with:
• The amount of information given by doctors
• The type of information given by doctors
• The language used by doctors
• There are differences in priorities between doctors and patients
• There are problems with patient recall and understanding
• Patients adherence and concordance with treatment plans
What aids patient recall
1) If its linked to pre-existing knowledge
2) Knowledge is re-inforced and tested
3) Use language the patient understands and avoid jargon
4) Be specific not vague
Types of explanation
Breaking bad new, handover, motivational interview, communicating about risk and shared decision making.
Steps in giving information
1) Summarise your understanding of the patients problems and/or task
2) Explore patient’s ideas, concerns and expectations
3) Identify patient’s starting point and desire for information
4) Signpost the information you plan to give
5) Give information in chunks and check understanding
6) Label important information
7) Use appropriate language
8) Use drawing and leaflets
9) Check patients understanding
Pre-clinical trial
A pre-clinical study can be in-vitro studies or studies on nonhuman animals. This helps to find preliminary data on efficacy, toxicity, pharmacokinetics (how the body processes drugs) and pharmacodynamics.
Bias
A systematic deviation of the results of a study from the truth because of the way it was conducted, analysed or reported.
Types of bias
- Selection - bias when allocating RPs to groups
- Performance - bias when providing care- eliminated in double blind trial
- Detection - bias when assessing outcomes, eliminated in double blind trial
- Attrition bias - differences between groups that withdrawal from the trial
- Reporting bias - selective revealing of information, differences between reported and unreported findings
- Recall bias - inaccurate recollections
Dissemination of information
All research papers should be reported and publicly available, including all negative results
The requirements of a good clinical trial
- No bias
- Consent from patients
- Dissemination of information
- Statistical analysis
- Ethical consideration (9 steps)
The 9 steps for ensuring good ethics in a clinical trial
- Value - enhancements of health must be derived from the research
- Scientific validity - research must be methodologically rigorous
- Fair subject selection - subjects selected on scientific objectives, not privilege or vulnerability
- Favourable risk-benefit ratio - risks must be minimised and benefits be enhanced i.e. the benfit must outweigh the risks
- Independent review - unaffiliated individuals must review the research and either approve/amend or terminate it
- Informed consent – research participants should be informed and be able to give competent and voluntary consent
- Respect for subjects - subjects should have their privacy protected, be able to withdraw, and have their health monitored
- Transparency - subjects should be made fully aware of the research aims, funding and benefits
True endpoints
The occurrence of a disease, symptom, sign or laboratory abnormality that constitutes one of the main target outcomes for a trial. I.e. a new cancer drug is shown to reduce tumour growth.
Surrogate endpoint
A measure of the effect of a treatment on a result that may correlate with a true endpoint but we cant be sure that this is a guaranteed relationship.
Example of surrogate endpoint
E.g. PSA biomarker levels for prostate cancer cell growth
High PSA = high tumour growth = decreased patient survival
Therefore PSA levels can be used as a surrogate endpoint for tumour growth/patient survival - but we cant be sure this is a causal relationship as there may be other factors
Disadvantages of surrogate endpoint
May not reflect outcomes that are important in improving patient survival. The hypothesis of how the surrogate endpoint relates to the disease may also be incorrect.
Disadvantages of true endpoints
1) May take too long to measure i.e. life expectancy
2) Can be more expensive
3) May be hard to measure i.e. pain
Observational studies
Case-control studies, cohort studies and cross-sectional studies.
Interventional/experimental studies
Randomised control trial
Advantages and disadvantages of a randomised control trial
- Advantages- can evaluate a single variable well, not much bias, can use meta-analysis
- Disadvantages- expensive and time consuming, ethically denies one group of treatment. Though the drug might be effective it may not prevent deaths
Advantages and disadvantages of cross sectional studies
- Advantages- quick, inexpensive and ethically safe
- Disadvantages- recall bias, no causation, selection bias, may be unethical (subjecting healthy people to gastroscopy), confounding bias
Advantages and disadvantages of cohort study
- Advantages- ethically safe, can match research participants, best to study the effect of risk factors on an outcome, can establish timing of evets.
- Disadvantages- controls are difficult to identify. Not that useful in rare disease’s as you need a large sample size and long follow up period. Exposure may be linked to a hidden factor.
Advantages and disadvantages of case control study
- Advantages- quick, easy, inexpensive, useful for studying rare diseases.
- Disadvantages- reliance on recall (recall bias), not necessarily causation, difficult to select control group (confounding bias- the characteristics of the case and control group may not match up).
Confounding bias
A mixing of effects. When an investigator tries to determine the effect of an exposure on an outcome but actually measures the effect of another factor.
Phase 0 studies
Tests interventions and methods that might be used in later phases, for example to determine how drugs work and how they can be administered.
Phase 1 studies
The first tests of new interventions and involve a small number of individuals, usually healthy young males with the aims to evaluate the risks, correct dosage and evaluate the pharmacokinetics and pharmacodynamics of new treatment.
Phase 2 studies
Involve a greater number of people. They aim to evaluate whether there is any evidence that the treatment might be beneficial, as well as to generate more data on risks. Some are RCTs.
Phase 3 studies
Involve a large number of patients. They frequently randomise them to the new treatment or to a control, which might be standard existing treatment or a placebo. They aim to provide conclusive evidence of the efficacy of treatments.
Phase 4 studies
(post-approval and post-marketing) studies evaluate interventions that are already used as treatments in clinical practice, particularly for their long-term effects.
Why are double blind trials ideal
They minimise performance bias and assessment bias
Different types of blind trials
- Open trials- researchers and participants known which arm they are allocated to
- Single-blind trial= only researchers known which arm participants have been allocated to
- Double-blind trial= both researchers and participants lack knowledge about which arm they have been allocated to till outcomes are measured.
Analysing data
The null hypothesis (H0) is the assumption that both arms will be equally effective. If the results suggest H0 is wrong, you need to work out the likelihood of this being due to chance. You calculate the P (probability) value, this is the probability of obtaining test results that are at least as extreme as the results that have been observed, assuming that the null hypothesis is correct. Once P is small enough, H0 can be rejected (as the likelihood of the results being the product of chance can be assumed to be very small). The results can then be said to be statistically significant.
Prevalence-incidence bias
Ignoring either severe or mild cases
Non-response bias
People who resonate with the survey and believe they have symptoms are more likely to respond
Ethical questions to consider in a trial
Is it ethical to have a washout period to avoid interference?
Is it ethical to jeopardise the validity of the study by allowing patients to drop out?
Is all data needed?
Do benefits outweigh risks?
Voluntary consent
The decision to consent or not consent to treatment is made by the patient and is not pressured by medical staff, friends or family
Informed consent
The process in which a healthcare provider educates a patient about the risks, benefits and alternatives of a procedure
Understood consent
Must understand the risks and benefits of a given procedure or treatment.
Capacity for consent
The person must be capable of giving consent, meaning they understand the information given and can use it to make an informed decision
