Gastro Oesophageal Reflux Disease

A condition that develops when the reflux of gastric content causes troublesome symptoms or complications Retrograde flow Occasional episodes common and normal in healthy individuals, usually after meals o Protective mechanisms- clearance mechanisms (peristaltic waves, gravity, alkaline saliva, bicarbonate secretion), healthy anti-reflux mechanisms Healthy anti-reflux mechanisms o Lower oesophageal sphincter tone o Contraction of the diaphragm around the oesophagus acting as an external sphincter o Folds of the gastric mucosa at the gastro-oesophageal junction o Steep angle between the oesophagus and the stomach Disease results when normal anti-reflux and clearance mechanisms fail oesophageal mucosa is exposed to gastric contents for prolonged periods of time. A problem of excessive exposure to gastric contents. Significant impairment of quality of life symptoms occur on two or more days a week

Factors associated with the development of GORD Abnormalities of the lower oesophageal sphincter o Inappropriate sphincter relaxation, lower oesophageal sphincter tone Hiatus hernia o Protrusion of a part of the stomach upward through the diaphragm o Pressure gradient is lost o Steep angle between stomach and oesophagus disappears o Some patients may have hiatus hernia without reflux Delayed oesophageal clearance o Defective peristaltic activity Delayed gastric emptying o 10-15% of GORD patients Increase intra-abdominal pressure o Pregnancy, obesity (x3), gastric distension Gastric contents o Gastric acid is the most important irritant Disease o Scleroderma-like disease o Asthma and cystic fibrosis Environmental factors- smoking Long term supine patients- stroke patients

Drugs o Nitrates o Calcium channel blockers o NSAIDs (inc. low dose aspirin) o Anticholinergics o Benzodiazepines o Beta agonists o Dopamine and levodopa o Oestrogens and progesterone o Narcotics o Alendronate, risedronate Diet Foods associated with reduced lower oesophageal tone o Peppermint, spearmint o Chocolate o Spicy and fatty meals protein rich meals increase lower oesophageal sphincter tone o Coffee, tea, cola drinks o Alcohol o Carbonated drinks o Citrus fruits o Tomato juice/paste o Onions, garlic

Typical symptoms of GORD Heartburn- burning sensation rising up form the stomach or lower chest towards the neck Regurgitation of sour/bitter material into the mouth Waterbrash- sudden flooding of the mouth with saliva Excessive belching Recurrence of symptoms/severity of symptoms Typical symptoms may be absent- diagnosis by atypical symptoms

Atypical symptoms of GORD Extra-oesophageal o Pulmonary asthma, chronic bronchitis, aspiration pneumonia, sleep apnoea, dyspnoea ENT o Chronic cough, hoarseness, dysphonia, enamel erosion, halitosis, pharyngitis, globus Other o Non-cardiac chest pain, chronic hiccoughs, nausea

Alarm symptoms of GORD Continual pain Dysphagia Odynophagia Unexplained weight loss Haematemesis/anaemia Choking attacks Recurrent vomiting Abdominal mass

Complications of GORD Oesophageal o Severe ulcerative oesophagus o Reflux-induced oesophageal stricture o Barretts oesophagus metaplasia of squamous oesophageal epithelium to columnar epithelium and intestinal lining cells. Normal pearly white oesophageal epithelium is replaced by the salmon pink colour of the stomach epithelium. The metaplasia moves up the entire circumference of the oesophagus (1-6cms) or in tongues and/or islands of Barretts with normal squamous lining in between o Oesophageal cancer o These patients need long term PPI (standard or high dose) Endoscopy o Limitation: patients have symptoms by endoscope is normal in > 50% o Indicated for Diagnosis is unclear Patients who have alarm symptoms Symptoms progress or persist on therapy Recent onset in > 55 years old H.pylori status done at the same time

Treatment of GORD Non-pharmacological and pharmacological Rationale for drug treatment o Relieve symptoms and improve quality of life o Heal erosions and ulcerations o Prevent/reduce risk of complications Stop aggravating foods Stop/ substitute aggravating drugs if possible Modify behaviour re: lifestyle precipitants Size and timing of meals Clothing restrictive

Elevation of bed head nocturnal symptoms (10-15cm block under the bedpost at heat of pillow) Antacids +/- alginic acid o Fast acting but short duration of action o Liquid faster acting than solids but inconvenient o Optimum: 1-3 hours after food o Al; constipation, Mg: diarrhoea, Na: BP o Chelators (2 hours apart) H2 Antagonists o Cimetidine, ranitidine, famotidine, nizatidine o Ranitidine preferred in pregnancy o Less effective than PPIs o More rapid onset of action than PPIs o Useful if response to PPI inadequate or unsuitable o Nocturnal symptoms Proton pump inhibitors o Omeprazole, esomeprazole, pantoprazole, lansoprazole, rabeprazole o OTC (low dose) o Most effective for controlling symptoms and healing inflammation full effect: a few days o All equivalent but can switch if response is inadequate o Timing of dose important 15-30 minutes before food! o Side effects Generally well tolerated Common: headache, GI symptoms Infrequent: decreased absorption of B12 with long term use Rare but important: myalgia, interstitial nephritis, hepatitis, skin reactions, Low Mg Risk of long term acid suppression o Absolute risk of the complications is very low Bacterial gastroenteritis Community acquired pneumonia Osteoporosis and hip fracture Bacterial overgrowth in the small intestine Outbreaks of clostridium difficile colitis in hospitalised elderly

Dyspepsia and Peptic Ulcer disease

Dyspepsia is a vague feeling of epigastric discomfort after eating, uncomfortable feeling of fullness (early satiety), bloating, nausea, heartburn, excessive belching persistent and/or recurrent Causes of dyspepsia

No obvious cause- functional dyspepsia (30%) uninvestigated, nonulcer dyspepsia GI diseases o Peptic or duodenal ulceration (Hp ass) o Gastro-oesophageal reflux disease o Gastric cancer Other miscellaneous GI disease o Biliary tract disease, pancreatitis, gastroparesis Non-GI diseases o Diabetes mellitus, thyroid disease Psychosocial factors- anxiety and depression Drugs o NSAIDs, metformin, iron salts, nitrates, erythromycin, bisphosphonates, corticosteroids, Ca channel blockers Herbal medicines o Garlic, ginkgo, saw palmetto, feverfew Lifestyle issues o Rich, spicy, fried food; gas producing foods eg. Cabbage, beans, onions o Obesity, smoking, excessive alcohol, coffee

Strategies for the treatment of dyspepsia Alarm symptoms (similar to PUD) o Referral for early endoscopy For dyspepsia not needing referral o Review medication offending drugs or herbal products o Address lifestyle issues low fat diet, avoidance of coffee, alcohol and aggravating foods, smoking cessation, weight loss, minimising stress Drug therapy o Antacids prn use o Anti-secretory therapy PPIs (full dose for 4 weeks, if no response increase dose or switch drug class for a further 4 weeks) H2 antagonists o Prokinetic drugs- dysmotility-like disorder Domperidone 10-20mg tds to qid prior to meals Metoclopramide 10mg every 4-6 hours (short term use) o Antidepressant- low dose TCA o Antispasmodic- mebeverine, peppermint oil Test for H pylori and treat if present o Non invasive H pylori test- urea breath test

Peptic Ulcer

A condition in which there is a circumscribed eroded segment in the GI mucosa (typically in the stomach and duodenum), which penetrates through the muscularis mucosae. Peptic ulcers may lead to bleeding or perforation, emergency situations

Causes of PUD Helicobacter pylori infection o 90% of DU and 80% of GU are associated with Hp NSAIDs (including low dose aspirin) o 15% of GU and 5% of DU among chronic NSAID users o Critical illness in hospitalised patients stress ulcers, patients with multi organ failure, major burns, multiple trauma, sepsis Zollinger-Ellison Syndrome (rare) o Malignant tumour on the pancreas or duodenum; overproduction of gastrin and acid

Clinical manifestations of PUD Intermittent epigastric pain or discomfort o Gnawing or burning o 1-3 hours after eating and relieved by food o Often relieved with antacids Non-specific o Heartburn, bloating, belching o Nausea and occasional vomiting Nocturnal wakening with epigastric pain Remitting, relapsing course Pain does not correlate with severity o Recurrence of pain o Change in pain pattern o May be asymptomatic and then present with complications GI bleeding o Insidious (occult blood in stools, +ve faecal occult blood test) o Sudden, severe and without warning (haematemesis, melena, weakness, syncope, increased urea) Penetration into an adjacent organ o Intense and persistent pain, radiating to other sites Gastric outlet obstruction (2%) o Bloating, fullness, large volume vomiting Stomach cancer (sequela) o 5% of gastric ulcers are malignant- Hp is a grade 1 carcinogen o 43% of the global burden of gastric cancers due to Hp

Alarm symptoms in PUD Unintentional weight loss

Iron-deficiency anaemia Haematemesis and melena Dysphagia and odynophagia Persistent vomiting Abdominal mass Over the age of 45 years at onset of disease (at higher risk of malignancy) On NSAIDs or warfarin

Pathogenicity of H. pylori Complex interplay of host factors and bacterial virulence Some strains are more virulent than others (CagA, VacA) Direct mucosal damage (lipases, proteases, urease) Altered inflammatory response o TNF- alpha, other cytokines stimulate gastric acid production directly. Inhibits somatostatin (inhibitory effect on gastrin) o Hypergastrinemia leading to increased acid secretion Transmission: oral-oral, oro-faecal o Risk factors for acquiring Hp include overcrowding, poor hygiene, and sharing of beds by siblings

Diagnosis of H. pylori Invasive method o Culture, histology, cytology and rapid urease test from biopsy specimens obtained during endoscopy Non-invasive methods o Serology (blood test for antibodies) o Urea breath test test and treat, after Hp eradication Faecal antigen test Urea breath test (96-98% accurate) o Urease is not present in human cells, its detection means that a urease producing organism (Hp) is present o Patient swallows a 14C-urea capsule o Capsule comes in contact with gastric mucosa o If urease is present, it splits the urea into CO2 and NH3. CO2 is absorbed into the stomach lining and exhaled in the breath as labelled 14CO2 o Breath samples are collected at a timed sequence of 6,12, 20 minutes after ingestion of the capsule o The breath samples are then analysed with a liquid scintillation counter for the level of radioactivity

General principles of treatment of PUD Relieve pain- symptomatic relief with antacids Heal ulcer with anti-secretory agents Remove aggravating factors- drugs, smoking, alcohol

Treat complications anaemia, other acute complications Prevent recurrence with eradication

H. Pylori eradication regimens First line therapy: triple therapy o Omeprazole 20mg bd + clarithromycin 500mg bd + Amoxycillin 1g bd- all for 7 days o For patients allergic to penicillin Substitute Amoxycillin with metronidazole 400mg bd o If clarithromycin is unsuitable Omeprazole 20mg bd + Amoxycillin 500mg tds + metronidazole 400mg tds all for 14 days o Other PPIs are equally effective True re-infection is uncommon after successful eradication Reasons why first line eradication might fail o Compliance o Resistance What if first line fails? o Ideally treatment should be guided by sensitivity testing o PPI based triple therapy using different antibacterial combination to initial treatment o Quadruple therapy PPI, bismuth, metronidazole, tetracycline for 10-14 days. Compliance poor What if both first line and second line fail? o Microbiological culture and sensitivity testing After Hp eradication o Post-testing with UBT Not for every case Complicated ulcer disease Cessation of maintenance treatment Patient preference o Maintenance therapy with PPI Usually unnecessary Hp eradication not successful or practicable NSAIDs required Standard dose

Pathogenesis of NSAIDs in PUD NSAIDs cause mucosal damage by two important mechanisms o Direct irritation of the gastric mucosa o Systemic inhibition of protective mucosal prostaglandin (PG) synthesis (main cause) Greatest risk within the first 3 months of treatment although risk continues to increase slowly and steadily with continued treatment

Peptic ulcers induced by NSAIDs are gastric, often silent, and present with a complication

Major risk factors for peptic ulcer disease with NSAID use Risk factor Prior history of ulcers Older age > 65 Anticoagulation or corticosteroid therapy High dose/multiple NSAIDs SSRIs Duration of therapy Alcohol and smoking H pylori infection Prevention of NSAID-induced ulcers Simple analgesics and physical treatment NSAID- least toxic, lowest dose, shortest half-life, use for as short a time as possible Test and treat before NSAID use Eradicated H.pylori in patients with a past history of ulcer disease before NSAID use Pharmaceutical prophylaxis o Patients with one or more risk factors Standard dose PPI Double dose H2 antagonists Misoprostol (poorly tolerated) Use of COX-2 selective NSAIDs celecoxib, etoricoxib o Selective COX-2 inhibitors reduce BUT do not eliminate GI events Concurrent use of low dose aspirin negates any possible risk reduction o Increase risk of cardiovascular events Increased risk 2.5 to 4 x 2.0- 3.5 x 2-3 x 2.5 x vs. low dose Age > 80, previous GI bleed, low dose aspirin, NSAIDs From 28 days to 1 year increased risk from 1.5 to 2.2 1.5-2 x 3.5 x

Treatment of NSAID-induced ulcers Cessation of NSAID and avoid in the future if possible Simple analgesics, physical treatment Healing of the ulcer with a PPI or H2 antagonists full dose for 2 months Test and treat for Hp after ulcer has healed If NSAID still required choice of NSAID, duration of treatment, concurrent use of PPI (does not prevent ulcer recurrence), assessment of other risk factors, advice on lifestyle factors

Asthma Chronic inflammatory disorder of the airways in which many cells & cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness & coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment. Asthma is defined by its clinical, physiological and pathological characteristics The predominant feature of the clinical history is episodic shortness of breath, particularly at night, often accompanied by cough. Wheezing appreciated on auscultation of the chest is the most common physical finding The main physiological feature of asthma is episodic airway obstruction characterized by expiratory airflow limitation.. The dominant pathological feature is airway inflammation, sometimes associated with airway structural changes The chronic inflammation is associated with airway hyper-responsiveness that leads to recurrent episodes of: Wheezing Chest tightness Shortness of breath with difficulty especially in breathing out Coughing especially at night or in the early morning These episodes are usually associated with widespread but variable airflow obstruction within the lung that is often reversible either spontaneously or with treatment This is in contrast to COPD, where obstruction is either not reversible or incompletely reversible, by bronchodilators

Pathogenesis of Asthma Smooth muscles constrict Inflammation, redness and swelling Increased mucous production Permanent changes in the airways can occur as a result of the inflammatory process Long term changes include o Increase in bronchial blood vessels o Increased smooth muscle o Thickening of collagen layers o Loss of normal distensability of the airway

Conceptual model for the immunopathogenesis of asthma. Exposure to allergen causes synthesis of IgE, which binds to mast cells in the airway mucosa. On reexposure to allergen, antigen-antibody interaction on mast cell surfaces triggers

release of mediators of anaphylaxis: histamine, tryptase, prostaglandin D2 (PGD2), leukotriene C4, and platelet-activating factor (PAF). These agents provoke contraction of airway smooth muscle, causing immediate bronchoconstriction, as reflected by a decline in FEV1 (forced expired volume in 1 second). Re-exposure to allergen also causes the synthesis and release of a variety of cytokines, such as interleukins 4 and 5, granulocyte-macrophage colony stimulating factor (GM-CSF), tumor necrosis factor (TNF), and tissue growth factor (TGF) from T cells and mast cells. These cytokines in turn attract and activate eosinophils and neutrophils, whose products include eosinophil cationic protein (ECP), major basic protein (MBP), proteases, and plateletactivating factor. These mediators cause the edema, mucus hypersecretion, smooth muscle contraction, and increase in bronchial reactivity associated with the late asthmatic response, indicated by a fall in FEV1 2-8 hours after the exposure. Signs and Symptoms Shortness of breath Wheezing Chest tightness Coughing Rapid breathing Stomach ache in young children Vomiting Increased pulse rate Upper airway symptoms Chest and throat muscles suck in Distress/panic Tired and lethargic Difficulty talking Blue lips

Trigger factors Inhaled allergens o Pollens when pollen levels are high, exposure may be reduced by staying indoors and closing all the doors and windows, especially during thunderstorms if allergic to grass pollen o House dust mite o Animal danders fungal allergens (mould) Tobacco smoke Respiratory infections Exercise Occupational factors Drugs e.g. royal jelly o Royal jelly and propolis are products from bees. There is evidence that taking royal jelly has caused very serious side effects in some people with asthma and other allergies. These have included

asthma attacks, breathing difficulties, anaphylactic shock and even death Oesophageal reflux Irritants

Diagnosis History o The presence of one or more of the following is suggestive of asthma: wheeze, cough, chest tightness, shortness of breath Physical examination o Hyperinflation and wheeze Supportive diagnostic testing, including spirometry Spirometry helps you to diagnose asthma and assess asthma control, by allowing you to: o assess change in airflow limitation o measure the degree of airflow limitation compared with predicted normal airflow (or with personal best in patients who have previously undergone spirometry). Spirometry is the lung function test of choice for diagnosing asthma and for assessing asthma control in response to treatment. Single or office-based measurements of peak expiratory flow (PEF) with conventional peak flow meters have significant limitations for assessing airflow limitation. A spirometer allows you to verify that the patient has performed the manoeuvre correctly and to generate a precise permanent record of results. Most adults, and children over 7 years old, can perform spirometry. Accurate measurement of respiratory function is necessary to assess and manage asthma. Measurements taken both before and after administration of a shortacting beta2 agonist (SABA) bronchodilator allow you to: o diagnose airflow limitation o measure the degree of airflow limitation o monitor the effects of treatment o demonstrate the presence and reversibility of airflow limitation to the patient o provide objective feedback to the patient about the presence and severity of asthma. FVC = the volume of air expired with maximal force FEV2 = the volume expired in the first second of maximal expiration after a maximal inspiration; is a useful measure of how quickly full lungs can be emptied

Peak Flow Measurement Portable Used to detect and measure a persons variation in best PEF, in order to assess variability of airflow limitation Not suitable for spirometry

Gives an idea of how narrow your airways are my measuring the maximum rate at which you can blow air into it Effort dependent Varies considerably between instruments Symptoms are related to occupational triggers e.g. industrial chemicals, wood dusts, flour

Classification of Asthma Daytime asthma symptoms Less than weekly More than weekly and less than daily Daily Night time symptoms Less than 2 per month More than two per month but not weekly Weekly or more often Exacerbations Spirometry Infrequent Brief Occasional May affect activity or sleep Occasional May affect activity or sleep frequent FEV1 at least 80% predicted FEV1variability < 20% FEV1 at least 80% predicted 20-30% FEV1 variability FEV1 60-80% predicted FEV1 variability > 30% FEV1 60% predicted or less FEV1 variability> 30%

Intermittent

Mild persistent Moderate persistent

Severe persistent

Daily Physical activity is restricted

frequent

Principles of Therapy Control therapy Achieve best lung function Maintain best lung function with the lowest effective doses of medication and the fewest possible adverse effects Good asthma control is defined as o Minimal symptoms during day and night o Minimal need for relieve medication o No exacerbations o No limitation of physical activity o Normal lung function (FEV1 and/ or Peak expiratory flow > 80% predicted or best)

Major Drug Groups Bronchodilators (relievers)

o Short acting beta 2 agonists (SABAS) o Eformetorol a LABA with a rapid onset of action o Ipratropium bromide o Theophylline Anti-inflammatory agents (preventers) o Inhaled corticosteroids o Leukotriene receptor antagonists o Cromones Long-acting beta 2 agonists (LABAS) (Symptom controllers) o Usually prescribed in comination with an ICS preventer

Bronchodilators Beta 2 Agonists Short acting salbutamol o Airomir, asmol, ventolin o MDI, DPI, nebuliser, oral liquid, injection o Combination with ipratropium (Combivent) Terbutaline o Bricanyl o DPI, nebuliser, oral liquid, injection Long acting eformoterol o Oxis turbuhaler o DPI only o Combination with budesonide (Symbicort DPI turbuhaler) Salmeterol o Serevent o MDI, DPI o Combination with fluticasone (seretide MDI or seretide DPI accuhaler Mode of action: relax bronchial smooth muscle by stimulating beta 2 receptors Any therapy that increases the level of intracellular cAMP can be expected to lead to bronchodilation. This is achieved by the increasing the production of cAMP (beta 2 agonists) or by inhibiting the breakdown of cAMP (theophylline) Short acting beta 2 agonists o Inhaler colour blue/grey o Acute asthma o Symptom relief during maintenance treatment of asthma and COPD o Protection against exercise induced asthma o Salbutamol and terbutaline have a rapid onset of action (5-15 minutes), short duration of action (3-6 hours) and similar efficacy Long acting beta 2 agonists (LABA) o Maintenance treatment of asthma (including nocturnal and exercise induced asthma) in patients receiving oral or ICS o Salmeterol and eformoterol have a long duration of action (over 12 hours) and similar efficacy

o Eformoterol has a quicker onset of action and is marketed for acute relief of symptoms in adults with asthma already receiving ICS and regular eformoterol is more expensive than SABA Beta 2 agonists adverse effects o Muscle tremor due to stimulation of beta 2 receptors in skeletal muscle. May be more troublesome in elderly patients o Tachycardia and palpitations are due to reflex cardiac stimulation secondary to peripheral vasodilation from direct stimulation of atrial beta 2 receptors (human heart has a relatively high proportion of beta 2 receptors) o Hypokalaemia is a potentially serious side effect. Is due to beta 2receptor stimulation of potassium entry into skeletal muscle, which may be secondary to a rise in insulin secretion. Hypokalaemia might be serious in the presence of hypoxia, as in acute asthma, when there may be a predisposition to cardiac arrhythmias Bronchodilators ipratropium o Inhaled anticholinergic bronchodilator o Competitively antagonises the effect of acetylcholine at M3 receptors o Is also used in combination with salbutamol o Maintenance treatment in COPD and severe asthma o Has a slower onset of action than other relievers Adverse effects ipratropium o Dry mouth, throat irritation o Urinary retention, constipation, palpitations, allergy o Patients using nebuliser solution should wear eye protection to decrease the potential for ocular side effects (blurred vision, dryness, irritation) Bronchodilators methylxanthines o Aminophylline and theophylline o Primary bronchodilatory effect due to non specific inhibition of phosphodiesterase isoenzymes. This prevents cAMP degradation in airway smooth cells and leads to smooth muscle relaxation o Methylxanthines also inhibit phosphodiesterase isoenzymes in inflammatory cells therefore have an anti-inflammatory effect Aminophylline indications o Severe airway obstruction - including acute asthma Theophylline indications o Maintenance treatment in severe asthma and COPD Methylxanthine drug-drug and drug-disease interactions o Macrolides o Fluvoxamine o Ciprofloxacin o GORD increased gastric acid secretion and relaxes sphincter o Arrhythmia, CHF may be exacerbated o Smoking increased theophylline clearance o Elderly clearance decreases with age o Epilepsy may lower seizure threshold

Methylxanthine adverse effects o NVD o Gastro-oesophageal reflux o Headache o Insomnia o Irritability o Anxiety o Tremor o Palpitations

Preventer Medications Corticosteroids Improve lung function and quality of life Decrease airway hyper-responsiveness Control airway inflammation Reduce frequency and severity of exacerbations Reduce asthma mortality Inhaler colours brown, red, orange Reduce/ control inflammation and sensitivity of airways Combine with receptor in cytoplasm Drug-receptor complex enters nucleus and controls synthesis of protein Increases the transcription of genes coding for the beta 2 receptor and a number of anti-inflammatory proteins e.g. IL-10, IL-12 Decreases the transcription of genes coding for many pro-inflammatory proteins e.g. IL-4, IL-5 etc Oral corticosteroids o Prednisolone, redipred or predmix are used as a rescue medication for asthma exacerbations o Liquid or tablet form o Generally used as a short course for 3-5 days as directed by a doctor portion of the ICS is deposited in the mouth, swallowed and absorbed from GIT and subjected to first-pass metabolism in the liver fluticasone and ciclesonide are subject to almost complete first pass metabolism whereas only about 85% of beclomethasone undergoes first pass therefore for fluticasone and ciclesonide, the cut absorbed drug can cause very little systemic activity and even for beclomethasone, the systemic activity due to gut absorption is low therefore inhaled steroid deposited in the lung is the main source for systemic absorption. There more drug deposited in the lung, the more the clinical activity increases but also the more the systemic absorption increases. The main site of absorption is from the alveoli and therefore smaller particles which tend to penetrate better into the alveoli are more likely to be absorbed and cause systemic side effects. Impaired lung function also has an effect on absorption of ICS.

Anti-inflammatory agents Cromones

cromolyns include cromoglycate, neodcromil sometimes called mast cell stabilisers act by inhibiting release of inflammatory mediators from mast cells indicated for the maintenance treatment of persistent asthma may be used as initial preventer therapy for children with frequent episodic to mild persistent asthma (also some adults), protection against exercise induced asthma disadvantage more frequent administration than ICS common side effects cough, throat irritation, bitter taste.

Anti-inflammatory agents leukotriene-receptor antagonists Montelukast (singulair) Leukotrienes are some of the most potent bronchoconstrictors known and are important mediators of inflammation in the airway Selective high affinity antagonists for the cyc-LT1 receptor It antagonises airway smooth muscle contraction and inflammation caused by leukotrienes Indications maintenance treatment of asthma, allergic rhinitis, prevention of exercise induced asthma In adults, LTRAs are less effective than low-mod doses of ICS in reducing symptoms such as night time waking and the need for rescue medication Less effective for improving lung function and quality of life Can be added to ICS to improve symptom control BUT improvement is less than achieved when LABA is added to ICS In children, LTRAs can be used as sole treatment in intermittent or mild persistent asthma are equally as effective as low dose ICS in mild persistent asthma Role of LTRAs have a small and variable bronchodilator effect, reduce symptoms including cough, improve lung function, reduce airway inflammation ad asthma exacerbations, alternative treatment for adults with mild persistent asthma and some patients with aspirin-sensitive asthma

Other anti-inflammatory agents Zileutin is a leukotriene synthesis inhibitor Potent inhibitor of 5-lipoxygenase activity Inhibits formation of all 5-lipoxygenase products including o LTB4 - potent chemotactic o LTC4, LTD4 and LTE4 Rare side effects churg-strauss syndrome o A type of vasculitis (blood vessel inflammation) that occurs throughout the body.

Anti-immunoglobulin Therapy Omalizumab (xolair) Recombinant humanised monoclonal antibody to IgE Prevents the release of inflammatory mediators

Indicated for the treatment of mod-severe allergic asthma in patients treated with ICS and with raised serum IgE levels Side effects injection site reactions, anaphylaxis (rare) Concern malignant neoplasms

Inhaler devices Large volume spacer decreases the amount of drug deposited on oropharynx, thereby decreasing the amount swallowed and absorbed from GIT, therefore limiting systemic effects Spacers used with MDIs (require less hand-breath coordination) o Improve pulmonary deposition pattern o Decrease oropharyngeal deposition and side effects candidiasis, dysphonia o Decreased risk of triggering cough reflex Metered dose inhaler deposition depends mainly on hand-lung coordination (inspiratory force has no effect) o Need good hand-breath coordination (not for children less than 810 years or poor dexterity) o Autohaler (e.g. airomir autohaler) is a breath-activated MDI can be used in for children over 5-7 years or poor hand breath coordination Dry-powder inhaler deliver drug in powder form. Deposition in lung depends mainly on inspiratory force (are breath activated) o Turbuhaler symbicort o Accuhaler seretide o Aerolizer foralide caps (eformoterol) o Handihaler - spiriva Both turbuhaler and accuhaler show acceptable drug delivery at inspiratory flow rates > 30L/min Nebulisers no longer commonly used o Important factors: nebuliser bowls should be replaced regularly, correct cleaning and maintenance o Can be used for children in any age group BUT spacers are the preferred and more efficient mode of delivery even in infants

Goals for successful management of asthma Achieve and maintain control of symptoms Maintain normal activity levels, including exercise Maintain pulmonary function as close to normal as possible Prevent exacerbations Avoid side effects Prevent asthma mortality

Principles of Therapy Reliever therapy for all patients with symptomatic asthma Initiate ICS for patients o Use of SABA more than 2 days/week and/or

o Night-time symptoms more than 1x/week and/or o Acute exacerbations at least monthly and/or o Restricted physical activity Dose depends on asthma classification o Mild-to-moderate: 200-400g BUD/day or equivalent o The therapeutic effect will usually be seen within 3-4 weeks Add LABA for patients not achieving adequate control Severe persistent asthma o Higher ICS doses may improve lung function/ decrease oral steroid use Other add-on therapy o LTRAs o Theophylline o Short-acting anticholinergics o Cromones Back-titration o After 6-12 weeks of good control

First aid for asthma Sit person down comfortably 4 puffs of reliever o without spacer take 1 puff, hold breath for 4 seconds, take 4 normal breaths and repeat until 4 puffs have been taken o with spacer 1 puff into spacer, ask person to breathe in and out normally for about 4 breaths. Repeat in quick succession until 4 puffs given wait 4 minutes if no improvement, give another 4 puffs if little or no improvement, call ambulance (000) keep giving 4 puffs every 4 minutes until the ambulance arrives

Acute asthma treatment of an acute, severe attack hospital admission oxygen to maintain SpO2 above 95% bronchodilator treatment SABA via MDI/nebuliser +/- ipratropium bromide corticosteroids oral (prednisone/prednisolone) or IV hydrocortisone theophylline/ aminophylline adrenaline anaphylaxis or imminent cardiorespiratory arrest IV magnesium consider if poor response to initial treatment

Ongoing care Reassess regularly Vaccination? Self-management

o Written asthma action plan signs of worsening control + instructions for how to respond reduce absenses from work, hospital admissions/GP visits, SABA use, and improve lung function S.M.A.R.T. Symbicort (budesonide and eformoterol) maintenance and reliever therapy Can be used as both a maintenance and reliever medication due to fastacting eformoterol Involves taking a maintenance dose of symbicort morning and night If further symptoms occur, can take additional inhalations as needed, to provide symptom relief No more than 6 inhalations on any one occasion Total of more than 8 doses/day should not be needed Up to 12 daily doses can be used temporarily 400mcg budesonide/12mcg eformoterol strength should not be used for the SMART regime

exercise induced asthma the amount of physical activity required to trigger asthma symptoms depends on level of fitness of the person bronchoconstriction triggered by exercise can be prevented by regular ICS is the most effective, an adequate warm-up may help if these measures are not adequate, or in children who dont need regular ICS for control of other symptoms o SABA - salbutamol 100 to 400 micrograms by inhalation, 5 minutes before exercise; terbutaline 500 to 1000 micrograms by inhalation, 5 minutes before exercise o LTRA o Cromolyn - montelukast 10 mg (child 2 to 5 years: 4 mg; 6 to 14 years: 5 mg) orally, daily, or 1 to 2 hours before exercise; nedocromil sodium 4 to 8 mg by inhalation, 5 to 10 minutes before exercise; sodium cromoglycate 10 to 20 mg by inhalation, 5 to 10 minutes before exercise. Titrate individual doses to achieve optimal effect LABAs are not recommended to prevent exercise induced asthma Inflammatory Bowel Disease Inflammatory bowel disease Chronic, relapsing, remitting inflammation at various sites of the GI tract Worldwide distribution, both men and women affected Increasing prevalence in western society over last 30 years o Jewish persons of European decent (x4) o Lower incidence in Africa, Asia and south America Peak incidence occurs in the second or third decade of life

Proposed causes of IBD Genetic factors o High concordance rate between identical twins o 15-35 fold increase in risk in first degree relatives for Crohns and 6-9 fold for ulcerative colitis o gene predisposing to CD has recently been isolated CARD 15/NOD2 drugs o NSAIDs (acute attack or relapse) Immunologic mechanisms o IBD responsive to immunosuppressants Infectious factors o Viruses, bacteria (E.Coli), mycobacteria no definitive role Environmental and psychological factors o Diet, smoking, stress, emotional or physical trauma The IBD hygiene hypothesis o Prevalent in highly industrialised temperate regions in contrast to less developed regions o Extremely hygienic conditions predispose to immunological diseases as immune system is not appropriately challenged o Parasites and worms

Ulcerative Colitis Inflammation only affects the superficial mucosa Mainly affects the rectum and distal colon but may extend to involved the entire colonic mucosa Inflammation tend to be continuous rather than patchy Rectum often involved

Epidemiology of Ulcerative Colitis Prevalence 60-70 per 100,000 More common o Non-smokers o Females o In whites v.s non-whites (x4) 10% of family members within 2 generations also have the disease 10% concordance in identical twins usually develops between 25 and 45 years of age

Ulcerative colitis and smoking more common in non-smokers and ex-smokers 90% of patients are non-smokers non-smokers are at 3.5 times greater risk than smokers to suffer from ulcerative colitis some smokers with ulcerative colitis have a relapse when they stop smoking

Symptoms of Ulcerative Colitis Colonic Symptoms Chronic diarrhoea Rectal bleeding Abdominal pain Urgency Tenesmus straining Severity of Ulcerative Colitis Mild % of cases Site 60% Distal colon and rectum progression into the remainder of colon in 15% of patients Intermittent, 35/day often without cramping pain Absent Usually absent Absent Normal Moderately Severe 25% Usually involves 1/3 to of the colon Total involvement in 30% of patients More than 5/day with gross blood and cramping pain Intermittent up to 38 degrees Intermittent during exacerbations Intermittent fatigue, increased sleep requirement Tenderness over colon Severe 15% Usually involves entire colon Systemic symptoms Tiredness Weight loss Malaise Fever

Diarrhoea

Profuse or constant liquid stools with blood Present 38-40 degrees Severe and persistent Extreme fatigue, weakness, prostration Distended abdomen, tympany, bowel sounds often absent Leucocytosis (> 20 x 108/L) Moderate to severe anaemia Hypoalbuminaemia Elevated alkaline phosphatase

Fever Anorexia and weight loss Systemic symptoms Physical examination

Laboratory tests

Usually normal

Mild intermittent anaemia Normal serum albumin Elevated alkaline phosphatase

Drug treatment of IBD inducing remission

o choice of drug and route of administration is guided by location, extent, severity and complications of disease as well as response to current or previous treatment maintaining remission o in order of preference aminosalicylate, azathioprine, mercaptopurine, cyclosporine o corticosteroids are NOT USED FOR MAINTENANCE

Inducing remission Corticosteroids Hydrocortisone, prednisolone IV for severe cases Oral formulation if extensive disease Topical formulation (splenic flexure) suppositories, rectal foam, enema When disease remits, gradual reduction required over 4-6 weeks IMPORTANT ADVERSE EFFECTS Main role: inducing remission in acute disease Balsalazide, mesalazine, olsalazine, sulphasalazine Topical therapy effective in left sided disease Combination of rectal + oral more effective than either alone Rectal mesalazine more effective than rectal steroid or oral ASA Monitor LFTs, FBP and renal function tests IMPORTANT ADVERSE EFFECTS Main role is in maintenance of remission (controversial in CD) Azathioprine, 6-mercaptopurine, IV cyclosporine For disease not responsive to steroids or needing continuous steroid for control Slow onset 2-3 months (except for IV cyclosporin onset 1 week) IMPORTANT ADVERSE EFFECTS Main role for Azt and 6-mp: maintenance of remission IV infliximab For moderate to severe disease non responsive to conventional therapy Infusion reactions: fever, chills,

And/or Aminosalicylates, 5-ASA (topical or oral)

immunosuppressants

TNF- alpha antagonists

Anti-diarrhoeal Codeine, Loperamide

Antispasmodic Hyoscine butylbromide Crohns Disease

pruritus Delayed sensitivity 3-12 days after infusion muscle pain, itch, arthritis, fever, rash Reactivation of TB, Hep B Expensive DO NOT USE IN SEVERE DISEASE Toxic megacolon (medical emergency) Fever, increased neutrophils, increased heart rate, electrolyte disturbance Dehydration, weakness, mental changes Rebound tenderness, abdominal distension, absent bowel sounds Not recommended

chronic inflammation that may affect any part of the GI tract from mouth to anus inflammation may extend to all of the layers of the GI mucosa the pattern of inflammation is segmental rather than continuous (skip lesions) rectum often spared 45-70% of CD is ileocolonic

Epidemiology of Crohns Disease in Australia, the incidence is rising females slightly more than males familial tendency peak incidence at 30 years old and most disease is seen in 20-40 year olds 3-4 x more likely in smokers vs. non-smokers o higher chance of relapse o course of disease more severe twice as likely in OCP takers

Signs and Symptoms of Crohns disease patients often present with may years of slowly progressing non-specific symptoms, (e.g. mild non-bloody diarrhoea for many years, anorexia, mild anaemia, mild lower GI pain) Small bowel 15-30% of cases More than 90% Common Common Ileocolitis 45-70% of cases More than 90% Common Common Colitis 15-25% of cases More than 90% Very common Less common

Feature Diarrhoea Abdominal pain Malnutrition

Fistula Obstruction Perianal disease

10-20% 30-40% uncommon

30-50% 40-50% common

10-30% 10-20% Very common

Perianal disease: fissures, cracks, haemorrhoids, skin tags, perianal abscesses, fistulas Treatment of Crohns Disease smoking cessation Corticosteroids Budesonide capsules Formulated to deliver to ileum and ascending colon 2-4 weeks before effect do not take with grapefruit juice not used in UC expensive Methotrexate also used IV adalimumab if loss of response or intolerant to IV infliximab S/C adalimumab for use at home Loperamide Can be used with caution Binds bile salts Useful to reduce diarrhoea due to terminal ileal disease Metronidazole, ciprofloxacin First line treatment for perianal fistulae

Immunosuppressant TNF-alpha antagonists antidiarrhoeal cholestyramine Antibiotics

Maintenance of remission immunosuppressants first choice aminosalicylate commonly used value controversial CORTICOSTEROIDS NOT USED

Systemic complications of IBD Hepatic (7% of UC patients) chronic active hepatitis, fatty infiltration, sclerosing cholangitis Arthritis (25% of IBD patients) usually affects large joints, occasionally associated with ankylosing spondylitis Ocular (10% of IBD patients) uveitis, iritis Dermatological or mucosal (5% of IBD patients) erythema nodosum, pyroderma gangrenosum, aphthous ulcers, fistulae

Local Compliactions of IBD Ulcerative colitis Haemorrhoids Crohns disease Small bowel stricture and obstruction

Anal fissures Perianal abscesses Rectal bleeding Colonic stricture Colonic cancer Toxic megacoln (3%) Management of IBD

Fistulae Bleeding Malabsoprtion syndromes (may lead to retardation in children)

Treatment is palliative, no drugs modify the underlying pathological condition Treatment is largely determined by the severity of the disease and the number of complications that require management The aims of treatment are to increase the periods of remission, reduce the number of relapses and reduce the number of recurrences after surgery Severe colitis is a medical emergency and if treatment is not effective within 7 days, surgery is indicated

Surgery in IBD Treatment of complication draining abcesses, repairing fistulas, widening strictures and obstructions Resection removal of diseased portions o Sigmoidectomy o Colectomy o Proctocolectomy Restoring intestinal continuity performed at time of resection o Ileosigmoid anastomosis o Ileorectal anastomosis Creating an artificial opening at the surface of the abdominal wall stoma o Ileostomy o Colostomy

Irritable Bowel Syndrome IBS is a functional gastrointestinal disorder characterised by abdominal pain and disordered defecation Chronic, intermittent and recurrent disorder No biological marker to confirm diagnosis Nervous diarrhoea, functional diarrhoea, spastic colon, mucous colitis, chronic catarrhal diarrhoea, colonic enterospasm, irritable colon syndrome

Classic features of IBS Abdominal pain o Location often varies

o Dull or sharp and stabbing o Lasts minutes to hours, often relieved by defecation or passing wind Bloating o With or without abdominal distension o Worse by the end of the day o Offensive wind Change of bowel habits o Diarrhoea, constipation, or both often mixed or alternating Lower mucous in the stools, stinging stools, straining, urgency, tenesmus, sensation of incomplete evacuation Upper nausea, early satiety, dyspepsia Fatigue, lethargy, migraine, headache, backache, dyspareunia, dysmenorrhoea and urinary symptoms Anxiety and depression

Diagnosis of IBS In the past diagnosis of exclusion or waste-basket diagnosis o Time consuming (up to 2-3 years and 3 healthcare professionals to time of diagnosis) o Frustrating and worrying for patient o Expensive o Extensive and sophisticated investigation in IBS do not result in identification of more than 1% to 2% of cases of organic disease Symptoms that fit into the Rome III essential criteria diagnosis o Recurrent abdominal pain or discomfort and a marked change in bowel habit in the last 6 months (at least 3 days/month in last 3 months that started 6 months before diagnosis) o With two or more of the following: pain is relieved by defecation, onset of pain associated with a change in frequency of stools, onset of pain associated with a change in appearance of stools o Other symptoms such as straining, urgency, feeling of incomplete evacuation o Passage of mucous o Bloating or feeling of abdominal distension o Presence of these symptoms increases confidence in diagnosis and help to identify sub-groups of IBS Absence of alarm symptoms A thorough physical examination by the GP to exclude fever, abdominal mass, faecal blood on examination, evidence of anaemia, signs of bowel obstruction, active arthritis, erythema nodosum on shins Lab tests FBS, ESR, C-reactive protein, antibody testing for coeliac disease, thyroid function tests

Sub Classifications of IBS Diarrhoea predominant D-IBS Constipation predominant C-IBS Pain predominant P-IBS

However predominant symptoms can change over time, mixed and alternating Symptoms severity o Intensity, constancy, degree of psycho-social difficulties and frequency of health care utilisation o Mild 70% (little disability) o Moderate 25% (occasionally interferes with daily activities) o Severe 5% (considerably affects daily activities and daily QoL)

Clinical Features Suggesting Organic Disorders Rather Than IBS Onset of symptoms in later life (over 40) Frequent nocturnal waking with symptoms Family history of colon cancer, IBD or coeliac disease Recurrent vomiting Persistent diarrhoea Severe constipation Persistent mouth ulcers Modern approach research Symptoms of IBS not just from afferent sensory signals arising from a disordered gut BUT from a dysregulation of the complex bidirectional brain-gut axis Many factors may contribute to an altered brain-gut axis including o Physiological (endocrine and immune function) o Psychosocial (behaviour, personality, cognition, emotions) o Environmental parameters Bidirectional brain-gut axis o Gut to brain (afferent) feeling of pain with abnormal distension o Brain to gut (efferent) motility, secretion, immune function and blood flow o Major transmitter of the ENS is serotonin Progressive or worsening pain Rectal bleeding Fever Unexplained weight loss anaemia steatorrhoea

Serotonin 5-HT Enterochromaffin cells of the GI tract, release serotonin (5HT1P, 5HT3, 5HT4) in response to luminal factors such as food or mechanical distension 5HT4 receptor agonists useful in constipation tegaserod (withdrawn from the market in march 2007) 5HT3 antagonists useful in severe diarrhoea alosetron (use with caution not available in Australia)

Treatment of IBS symptom based approach

limitations o patients often report presence of more than one symptom global symptom relief should be primary outcome o lack of good clinical trails o placebo effects very high P-IBS o Primary complaint of pain o Anti-spasmodic agents Hyoscyamine butylbromide 20mg qid Mebeverine 135mg tds Peppermind oil 0.2mL/cap 2 caps tds o Antidepressants Amitriptyline, nortriptyline IBS associated with anxiety and depression Start at low dose (12.5-25mg nocte), increase over 2-3 weeks slowly, maintain for 6-12 months if beneficial Also reduce diarrhoea o SSRIs Often used but no real evidence Citalopram 20mg daily reduces abdominal pain, bloating and interference with daily living Fluoxetine 20mg daily C-IBS o Primary complaint of constipation o Fibre products Methylcellulose, psyllium, coarse bran, isphagula husk (choice depends on response) o Osmotic agents Lactulose, sorbitol o Stimulants Senna o Problems Insoluble fibre and osmotic agents can increase bloating (use of soluble fibre instead may help) Senna causes cramping o Insoluble fibre roughage; increase stool bulk and decrease transit time Vegetables, fruits, legumes, wholegrain wheat and oat, brown rice, bran, cereals, seeds o Soluble fibre high water holding capacity Psyllium, okra, apples, apricots, citrus fruits, cherries, figs o Bran or fibre Aggravates symptoms initially Start wit ha small dose that is titrated up slowly every week over 3-4 weeks until symptoms improve If one type does not help, try another Do not give up until an adequate trial has failed If bulking agent helps, continue indefinitely

Not recommended when bloating is a predominat complaint, when there is suspected or proven obstruction

D-IBS o Primary complaint of diarrhoea o Agents that slow colonic transit Loperamide 4-8mg ddd (max 16mg d) Diphenoxylate 2.5mg/atropine 25mcg 2 tds to qid (SE) Cholestyramine 4-8 g orally d or bd prn (DIs) o Trial of increasing fibre intake or intake of bulk forming agents o Trial of anticholinergic or anti-spasmodic drugs IBS with bloating o Primary complaint of bloating o Anticholinergic agents Hyoscyamine butylbromide 20mg qid Others charcoal, simethicone o Insoluble fibre e.g. bran does not help bloating o Dietary changes important Lifestyle modifications dietary changes o Predominantly constipation increase soluble fibre in diet (2040g per day) + other measures o Predominantly diarrhoea avoid large amounts of diet drinks and chewing gum, caffeine and alcohol. Trial lactose free diet (2 weeks) o Predominantly bloating reduce fibre, reduce air swallowing eat slowly, do not drink through straws, avoid gas producing foods Gas producing foods may cause problems for people with IBS o Lactose in milk and milk products o Cabbage, brussel sprouts, cauliflower o Legumes (dried peas, beans, lentils, etc) o Sorbitol and mannitol in stone fruits, in some low kilojoule foods Well established food culprits causing IBS o Fatty foods o Milk and milk products o Chocolate o Alcohol o Caffeinated drinks o Carbonated drinks o Other exacerbating factors include stress, antibiotics, NSAIDs Education and reassurance o Pathogenesis, symptoms, natural history of IBS o Establishment of a good patient/doctor relationship Exercise o Improves gastric emptying o Improves symptoms in patients with C-IBS o Lack of RCTs Stress of anxiety management o Cognitive behavioural therapy o Psychological counselling o hypnotherapy

Chronic Wounds

Wounds which have failed to heal in an orderly and timely process to restore function and structural integrity over a period of three months Pressure ulcers, arterial and venous ulcers, diabetic ulcers, cancer wounds, post-op wounds, entero-cutaneous fistulae Healing o Takes longer than 3 months (may never heal) o Loss of tissue, granulation tissue required o Not an orderly and timely process o Complicated and delyed by intrinsic and extrinsic factors o Underlying cause must be identified and treated

Modes of healing Primary intention o No/minimal tissue loss o Edges held together by clips, tape or sutures Delayed primary intention o Debris, requires cleaning prior to closure Secondary intention o Delayed by process of contraction, granulation, epithelialisation. Scarring results

Pressure ulcers Decubitus ulcers, bedsores Pressure ulcers are lesions caused by unrelieved pressure on the skin resulting in damage to underlying tissues The pressure is uaully from a bony prominence on one side and a hard surface on the other side Capillary-closing pressure: 32mmHg When this pressure is exceeded, blood flow in microvascular system is brought to zero and ischemia occurs The ischemia produced leads to tissue necrosis Factors contributing to skin breakdown o Pressure o Friction o Shearing o Maceration Who is at risk? o Limited mobility o Cognitive impairment o Elderly o Incontinence o Malnutrition o Chronic conditions such as diabetes or vascular disease o Residence in a nursing home

Staging of pressure ulcers o Stage 1 non-blanchable redness of intact skin. Reversible o Stage 2 partial thickness skin loss. Abrasion, blister, shallow crater. Reversible o Stage 3 full thickness skin loss. Damage and death of subcutaneous tissue. Deep crater. Life threatening o Stage 4 full thickness skin loss with extensive destruction to tissues and supporting structures. If infection sets in, may be fatal Prevention o Risk assessment assessment of general physical condition, activity, incontinence, mental state, mobility. Norton scale, braden scale o Use of appropriate pressure-relief surfaces sheepskins, egg crate mattresses, air-fluidised beds o Turning/repositioning of patients every 2 hours while lying, every hour while sitting o Systematic and regular skin inspection and assessment o Documenting interventions and outcomes Treatment o Pressure reduction frequent repositioning, specialised support services o Keep would clean of urine and faeces to prevent maceration and infection o Removal of necrotic tissue o Wound dressings Transparent film dressings e.g. tegaderm, opsite. Shallow stage 1,2,3 ulcers, minimal exudate Hydrocolloid dressings e.g. duoderm. Stage 1,2,3 and some 4, minimal exudate Alginate dressings. Stage 2,3,4 more exudative ulcers

Arterial Ulcers Problem of flow Arteries fail to deliver enough blood to the superficial tissues. As a result there is inadequate oxygen and the skin breaks down Ischaemic o Small, punctate ulcers that are usually well circumscribed o Can occur anywhere, but is frequently seen on the dorsum of the foot Pain Pulselessness of the extremity Cool or cold skin Delayed capillary return time usually 3 seconds or less Loss of digital and pedal hair Possible claudication cramp like pain in the calves Predisposing factors

o Arteriosclerosis o Atherosclerosis o Hypertension o History of CVD o Peripheral vascular disease o Obesity o Smoking Treatment o Increase the circulation ot the area surgically to revascularise o Treat the underlying problem o Keep the tissue base moist, infection free and void of necrotic debris o Appropriate wound dressings hydrogel, foam, hydrocolloid o Compression bandages are NOT appropriate

Venous Ulcers Ulcers resulting from damage to the venous system in the leg Veins of the calf muscles fail to pump the venous blood back to the heart Pressure increases in veins and capillaries and causes fluid to leak into the surrounding tissues Swelling develops interfering with oxygenation and nutrition of the tissues and ulcers form Haemoglobin from the red blood cells escapes and leaks into the extravascular space, causing the brownish discoloration commonly noted Near the medial malleolus Uneven edges, shallow Moderate pain Copious exudate Foot pulses present, foot is warm Pitting oedema often present and may predate ulcer In the long term, debris and subcutaneous tissue become indurate and fibrosed lipodermatosclerosis Predisposing factors o Varicose veins o Deep vein thrombosis o Chronic venous insufficiency o Sitting, standing for long periods o Poor calf muscle function o Obesity Treatment o Keep the ulcer infection free o Absorb any excess exudate o Supply compression 40mmHg Compression bandages Compression stockings o Zinc paste bandage

o Promote activity of the patient and the involved extremity o Management of the underlying problems Controlling the oedema is a primary concern o Oxpentifylline 400mg TDS to improve healing Increases effectiveness when used with compression

Diabetic Ulcers Diabetics are prone to foot ulcerations due to both neurologc and vascular complications Neuropathic, ischemic, compression Peripheral neuropathy can cause altered or complete loss of sensation in the foot Patient cannot identify that too much pressure is being placed in one area of the foot Any cuts or trauma to the foot can go completely unnoticed for days or weeks Tissue ischemia and necrosis result leading to plantar ulcerations Treatment o Good diabetic control o Disperse weight away from the ulcerative area orthopaedic evaluation, shoe modifications o Right choice of dressings hydrogel, foam, hydrocolloid, hydroactive o Proper wound assessment watch for sinus tracking and infection. Debridement of necrotic debris o Prevention of complications sepsis in ischaemic tissue predisposes to gangrene and consequently lead to amputation Predisposing factors o Duration of diease o Advanced age o Poorly controlled BSL o Smoking o Excessive alcohol use o Ill fitting shoes o Presence of PVD and/or neuropathy Prevention o Do not smoke o Inspect feet daily o Wash feet in warm water and dry thoroughly. Moisturise feet but not between toes o Avoid chemicals and corn plasters o Do not walk barefoot protective, well fitted closed-in shoes o Annual check-up with podiatrist nerve damage, circulation, skin, joint problems, nail clipping, footwear o Seek early medical assistance for wound or abnormality

Factors Affecting Wound Healing Intrinsic factors Age Health diseases, immune function Nutritional status balanced diet, hydration, Zn, Cu, Mn, Se, folic acid Body build emaciated, obese Extrinsic factors Mechanical stress Debris Temperature Desiccation/maceration Infection Chemical stress Medications lower immune response, increase risk of bleeding Lifestyle factors

Infected Wounds Presence of more than 105 microorganisms/g of tissue Redness, pain, greenish pus, offensive smell, warm to the touch Fever, malaise Silver sulfadiazine 1% cream prevention and treatment of infection Silver dressings release of silver up to seven days Systemic antibiotics

Use of Antiseptics Povidone-iodine, cetrimide, Chlorhexidine gluconate o Useful as preparatory solutions o Useful to clean grazes or other acute wounds o Toxic to fibroblasts o Should NOT be used on CHRONIC WOUNDS o No role in treating infections

Debridement of Wounds removal of dead, necrotic tissue Surgical/sharp Autolytic digested by endogenous enzymes, aided by hydrogel and hydrocolloid dressings Enzymatic collagenase, papain-urea derivatives Chemical cadexomer iodine products Mechanical use of damp dressings, irrigation under pressure