Treatment of Bronchial Asthma (Part 2) PDF

Treatment of Bronchial asthma (part 2) Semester III : [email protected] : [email protected] : 01068381663  Learning Outcomes By the end of the lecture, the students will be able to: 1. Describe the mechanism of action, uses & adverse...

Treatment of Bronchial asthma (part 2) Semester III : [email protected] : [email protected] : 01068381663  Learning Outcomes By the end of the lecture, the students will be able to: 1. Describe the mechanism of action, uses & adverse effects of corticosteroid used in treatment of bronchial asthma 2. Identify leukotriene receptor antagonists. 3. Identify stepwise approach used in treatment of different cases of BA 4. Describe the biological therapy used in treatment of bronchial asthma 5. List other drugs used in treatment of bronchial asthma 6. Identify management of acute sever asthma  Lecture Outline Corticosteroids Treatment of Bronchial asthma Anti-leukotriene Biological therapy Step wise approach in BA Treatment of acute sever asthma  Reduction of bronchial inflammation Anti inflammatory drugs Corticosteroids  They are anti-inflammatory & not bronchodilators  They increase airway diameter  Decrease frequency of asthmatic attacks  Decrease bronchial hyper-reactivity.  Corticosteroids (inhaled)  Inhaled corticosteroids (ICS) are the most effective controllers used in BA.  The only drugs that can effectively suppress the characteristic inflammation in asthmatic airways, even in low doses.  First-line therapy for all asthma severities and patients of all ages and are the most effective asthma medications currently available.  Corticosteroids Mechanism of action Corticosteroids can effectively ↓ bronchial inflammation and hyperreactivity through:  They inhibit phospholipase A2 enzyme →↓ synthesis of LTs, PGs& PAF.  Corticosteroids mechanism of action  Inhibit B cell function → ↓ antigen-antibody reaction.  Inhibit T cell functions → ↓ decrease the production of inflammatory cytokines e.g. IL and TNFα leading to inhibition of early phase response to allergen  Inhibit macrophage activity.  Inhibit mast cells → ↓ histamine release and capillary permeability.  Upregulation of B 2 receptors  Increase airway diameter, reverse the shedding of epithelial cells, goblet-cell hyperplasia and basement-membrane thickening characteristic of the airway mucosa of patients with asthma.  Corticosteroids mechanism of action Peter J.Barnes et.al,Pharmaceuticals 2010, 3, 514-540  Corticosteroids used in treatment of BA Corticosteroids used clinically in treatment of asthma: 1-Inhaled corticosteroids (ICS) :  Beclometasone, Budesonide  Combined with LABA in the same inhaler (Beclometasone-formoterol) (Betamethasone-formoterol) Inhaled corticosteroids  Inhaled corticosteroids Adverse effects of inhaled corticosteroids: 1-Oropharyngeal candidiasis: avoided by using spacing device or nystatin. 2-Dysphonia: leading to change of voice.  Corticosteroids 2- Oral corticosteroids : Prednisolone 3- IV Corticosteroids Hydrocortisone  Corticosteroids Adverse effects of systemic corticosteroids 1. Increased susceptibility to infection. 2. Osteoporosis 3. Fluid retention 4. Electrolyte imbalances (especially hypokalemia) 5. Raised blood pressure 6. Elevated blood glucose levels 7.Iatrogenic Cushing (moon face buffalo hump…..  Leukotriene receptor antagonist (LTRA)  Montelukast  Orally dosed drug ( a film-coated tablet, chewable tablet or oral granules) Mechanism of action  A highly selective leukotriene receptor antagonist binds with high affinity to leukotriene receptor for leukotrienes D4 and E4 secreted from inflammatory cells &involved in the inflammatory process that may cause asthma and allergic rhinitis signs.  Leukotriene receptor antagonist (LTRA) Adverse effects 1-Neuropsychiatric events : anxiety, depression, aggressiveness, agitation, ,memory impairment, sleeping disorders, seizures, paresthesia, hypoesthesia, suicidal thoughts. 2-Headache, fever, fatigue 3-Increased incidence of upper respiratory signs (rhinorrhea, pharyngitis, laryngitis, sinusitis)  Stepwise approach in treatment of bronchial asthma Track 1: Preferred controller and reliever (GINA 2024) Step 1&step 2: as needed low dose ICS-formoterol Step 3: low dose maintenance ICS-formoterol+ as needed low dose ICS-formoterol Step 4: medium dose maintenance ICS-formoterol+ as needed low dose ICS- formoterol Step 5: Add on LAMA Refer for assessment of phenotyping According to result Anti Ig E ,Anti- IL5/5R,anti Anti- IL4 R alpha(monoclonal) Consider high dose maintenance ICS-formoterol Continue reliever as needed low dose ICS-formoterol  Stepwise approach in treatment of bronchial asthma Track 1: Preferred controller and reliever (GINA 2024) Step 1&step 2:symptoms less than 3-5 a week with normal or mildly reduced lung function Step 3: symptoms most days or walken at night once a week or more or low lung function Step 4: Daily symptoms&walken at night once awake or more&low lung function or recent excerbations Step5: persistent step 4 despite treatment  Biological therapy Phenotyping  Severe asthma is a heterogeneous disease with different phenotypes  Patient poor control (stage 5) →Refer for phenotype assessment  Allergic phenotype (type I) with IgE-producing B cells →Consider monoclonal antibody against IgE  Eosinophilic phenotype (type 2) involves T‐helper 2 cells activation with abnormal production of type 2 cytokines (Interleukin (IL‐4, IL‐5 and IL‐13)→ Consider add on type 2 targeted biologic therapy  Biological therapy  Examples of biologic therapy Anti Ig E monoclonal antibodies Omalizumab (type 1 inflammation) Anti- IL5/anti 5R: Benralizumab (type 2 inflammation)  Biological therapy Omalizumab Anti Ig E monoclonal antibodies synthetized by recombinant DNA technology to block Ig E. Mechanism of action: 1-Omalizumab binds IgE and prevent its binding to Ig E receptors on mast cells. 2-It inhibits degranulation of mast cells and prevent the release of allergic mediators from them. 3-It lowers the plasma IgE to undetectable levels in about 10 weeks. Side effect : Anaphylaxis Quiz 2  Other drugs used in treatment of bronchial asthma for patients with persistent symptoms despite treatment Azithromycin: for patients with persistent symptoms despite treatment Mixture of oxygen (20%) and helium (80%): Heliox  Helium is an inert gas.  Its low density facilitates O2 diffusion through obstructed airways →↓ work of breathing.  Pure oxygen irritant  Treatment of acute severe asthma (status asthmatics) Acute attack of asthma in which bronchodilators are poorly effective in relieving the attack. Management  Hospital admission.  Oxygen: to maintain O2 saturation between 94-98%.  SABA+SAMA (ipratropium bromide) (nebulizer)  Prednisolone (40-50mg oral) if can’t take oral→ hydrocortisone: 100 mg IV / 6 hs.  IV magnesium sulphate infusion over 20 minute.  Correction of acidosis and dehydration by i.v. fluids.  Summary and wrap up  Antiflammatory drugs are important to decrease air way hyerresponsiveness  Cortcosteroids are the anti-inflammatory of choice in a case of BA (ICS+formoterol)  Cortcosteroids can be taken by inhalation (first line) oral or intravenous in acute attack  Biological theray is used in refractory cases of BA according to the results of phenotying  Stepwise approach is used for asthma management  Treatment of status asthmatics include oxygen therapy, inhaled β2 agonists, inhaled ipratropium bromide, corticosteroids, magnesium sulphate IV.  References & recommended readings 1-What’s new in GINA 2024? GINA 2024 update published 22 May 2024 Download from ginasthma.org https://ginasthma.org/wp-content/uploads/2024/06/Whats-New-In-GINA-2024- WEBSITE.pptx 2-Brenner, C.S. G. Brenner and Stevens’ Pharmacology. [ClinicalKey Student]. Retrieved from: https://clinicalkeymeded.elsevier.com/#/books/9780323391665/ 3- Wecker, L. Brody's Human Pharmacology. [ClinicalKey Student]. Retrieved from https://clinicalkeymeded.elsevier.com/#/books/9780323476522/ thanks Fo r Wa tc hin g Antibacterial drugs Intended learning outcomes Describe major classifications of antibacterial drugs Understand main mechanisms of bacterial drug resistance Classify β-Lactams antibiotics based on their spectrum of activity Describe mechanism of action, kinetics, mode of resistance and major side effects of β-Lactams Definition … Antimicrobial drugs → chemical substances (natural or synthetic) that suppress the growth of, or kill, microorganisms (bacteria, fungi, helminths, protozoa and viruses) Antibacterial drugs (Antibiotics) Classification of Antibacterial drugs  According to their mechanisms of action I. Cell wall Inhibitors  inhibition of bacterial cell wall synthesis β-Lactam Antibiotics, Glycopeptides II. Protein synthesis Inhibitors  disrupt bacterial ribosome function ○ Inhibitors of 30S ribosomal subunit  Aminoglycosides, Tetracyclines ○ Inhibitors of 50S ribosomal subunit  Macrolides, Linezolid, Clindamycin III. inhibitors of bacterial metabolic pathways Sulfamethoxazole-trimethoprim IV. Inhibitors of bacterial DNA or RNA synthesis Fluoroquinolones V. Disruptors of bacterial cell membrane  Bacteriostatic  inhibit bacterial growth but do not kill bacteria at concentrations that are safe for humans  natural immune mechanisms are required to eliminate the bacteria. Bacteriostatic drugs  less effective in immunocompromised patients Bactericidal → kill bacteria at plasma concentrations safe for humans  According to their spectrum of activity Gram Negative Bacilli B-lactamase Atypical Drugs Affecting the Cell Wall 1. β-Lactam antibiotics 2. Glycopeptides (Vancomycin) β-Lactam Antibiotics I. Penicillins II. Cephalosporins III. Carbapenems IV. Monobactams All β-Lactams  have a β-lactam ring  that must be intact for them to be active Most β-Lactams  susceptible to inactivation by bacterial β-lactamases  which split the β-lactam ring Cephalosporins, monobactams & carbapenems → have structural modifications  show some resistance to β- lactamases.  β-Lactams Mech. of action Bind to penicillin-binding proteins PBPs (transpeptidases) in bacteria, which is required for the last step of the bacterial cell wall synthesis (cross-linking of the peptidoglycan layer) → inhibit transpeptidation reaction → inhibits cell wall synthesis  bacterial cell swelling and rupture. Bacterial resistance to β-Lactams 1. Production of β-lactamases  destruct β-lactam ring There are hundreds of β-lactamases ○ Staph. aureus (Methicillin sensitive Staph. aureus (MSSA) ○ Gram-negative bacteria ○ Enterobacteria  release powerful β-lactamases (extended-spectrum β-lactamases (ESBLs)  can destruct cephalosporins & monobactams MRSA MSSA 2. Mutation in PBP  meticillin-resistant S. aureus (MRSA)  PBP2A  do not bind β-lactam antibiotics I. Penicillins Natural penicillins Animo-penicillins Anti-staph penicillins Antipseudomonal penicillins Penicillin G Amoxicillin +/- clavulanate Flucloxacillin Piperacillin + tazobactam Penicillin V Ampicillin +/- sulbactam Narrow spectrum Broad spectrum Narrow spectrum Extended spectrum  Penicillins Spectrum of activity 1. Natural 4. Anti-staph 2. Amino (Broad- 3. Anti- (MSSA) spectrum) pseudomonal Penicillin G & V Flucloxacillin Amoxicillin +/- Piperacillin/ Benzathine clavulanate tazobactam penicillin G Ampicillin +/- sulbactam G +VE cocci  As natural + As anti-staph + As broad + strep MSSA Listeria (+VE) + H. Pseudomonas (- Syphilis influenza & E.coli (-VE) VE) + anaerobes Benzathine penicillin G is long acting, given once /monthly as prophylactic against RF caused by strept.  β-lactamase inhibitors (Suicide group) Clavulanate, Sulbactam, Tazobactam No antibacterial effect. Inhibit β-lactamase to protect β-lactams from inactivation. Combined with β-lactams to be effective against β-lactamase producing organisms  MSSA Amoxicillin/clavulanate, ampicillin/sunbactam, piperacillin/tazobactam Penicillins Indications: Natural penicillins  Drug of choice for syphilis, pharyngitis. Anti-staph penicillins  skin and skin structure infections Amoxicillin  Drug of choice for acute otitis media and pharyngitis. Aminopenicillin-based combinations  Good for: 1. Empiric for mixed aerobic and anaerobic infections, such as intraabdominal infections or diabetic foot infections. 2. Upper respiratory tract infections& community acquired pneumonia (CAP) , urinary tract infections (UTI) Piperacillin/tazobactam  Empiric therapy for hospital acquired pneumonia, febrile neutropenia, complicated UTI, necrotizing skin infections, sepsis  Cephalosporins Cephalosporins → more resistant to hydrolysis by β-lactamases Classified into 5 generations As a rule, Successive generations  have ↑ activity against Gram -VE bacilli. Moving from the 1st to 3rd generations  ↓ Gram +VE activity & moving from 3rd to 5th generations  progressively ↑ Gram +VE activity again  Cephalosporins Spectrum of activity  Cephalosporins Spectrum of activity 1st gen 2nd gen 3rd gen 4th gen 5th gen Cefazolin Cefoxitin Cefotaxime Cefepime Ceftaroline Cephalexin Cefotetan Ceftriaxone Cefuroxime Ceftazidime As ampicillin As 1st gen + As 2nd gen + As 3rd gen + As 3rd gen + + MSSA ↑ –VE ↑ –VE Pseudomonas MRSA + + Anaerobes  Pseudomonas Cefoxitin,  Ceftazidime Cefotetan  Cephalosporins Indications 1st gen 2nd gen 3rd gen 4th gen Cefazolin  Cefuroxime  CAP, upper UTI, Hospital Skin infections Upper respiratory meningitis, gonorrhea acquired Prophylaxis to tract infections & Intraabdominal infections pneumonia prevent surgical site community- (in combination with Febrile infections. acquired metronidazole). neutropenia Cephalexin  pneumonia (CAP) Ceftazidime  Uncomplicated Cephamycins  Hospital acquired Lower UTI in intraabdominal pneumonia pregnancy. infections Febrile neutropenia Carbapenems and Monobactam Monobactam (Aztreonam) Spectrum of activity ==? limited to Gram-negative bacteria, including Pseudomonas. No cross-allergenicity with the penicillins  give safely to people with serious penicillin allergy Carapenems (Imipenem, meropenem) Extremely broad spectrum of activity  Gram +VE cocci + Gram -VE bacilli + Pseudomonas + anaerobes Inactive against MRSA.  Side effects of β-Lactams Safest of all antibiotics. GIT  Nausea, vomiting  most common with oral preparations GIT  same as Diarrhoea (Clostridium difficile-related colitis)  a result penicillins Cephalosporins of disturbance of normal colonic flora  broad-spectrum penicillins. Allergic reactions  common (5% of exposed Allergic reactions  Allergic individuals). History of anaphylaxis, reactions wheeze, or urticaria to Urticaria, wheeze and anaphylaxis (IgE-mediated reactions) penicillins  CI of Carbapenems Vasculitis (immune complex-mediated reactions). cephalosporins. Nonspecific maculopapular rash, and rare serious Stevens– Penicillins Johnson syndrome (T-cell-mediated allergy) Cross-allergenicity  with cephalosporins is < 2%; with carbapenems is < 1%; no cross-allergenicity with monobactams. Seizures Only Aminopenicillins → frequently produce a non-allergic maculopapular rash in people with glandular fever (infectious mononucleosis with Epstein-Barr virus) Glycopeptides (Vancomycin)  Mech. of action  binds to the terminal D-Ala-D-Ala Vancomycin portion of pentapeptide side chain  inhibit cross-linking of peptidoglycan  interfere with cell wall synthesis Spectrum  narrow spectrum → only against Gram +VE cocci + MRSA Uses  usually reserved for Drug of choice for MRSA infections (pneumonia, skin infections) IV Bacterial endocarditis not responding to other treatments  IV Treatment of C. difficile colitis  given orally TDM  Higher troughs have been associated with nephrotoxicity 26 Trough goals  15–20 μg/mL. Thank you  Treatment of Bronchial asthma (part 1) Semester III : [email protected] : [email protected] : 01068381663  Learning Outcomes By the end of the lecture, the students will be able to:  List different line of treatment of bronchial asthma  List different types of bronchodilators used in treatment of bronchial asthma  Identify mechanism of action, uses and side effects of beta 2 agonists  Identify mechanism of action, uses and side effects of anti- muscarinic drugs used in treatment of BA  Identify mechanism of action, uses and side effects of methylxanthines used in treatment of BA  Lecture Outline Pathogenesis of BA Lines of treatment of BA Treatment of Bronchial asthma Bronchodilators Beta 2 agonists Antimuscrinics Methylxanthines  Bronchial asthma Clinical picture  Recurrent episodes of shortness of breath (dyspnea) chest tightness and cough  Wheezes, hyerresonance on percussion Pathogenesis of bronchial asthma Air way obstruction Pathogenesis of bronchial asthma Air trapping 7  Pathogenesis of bronchial asthma  Chronic inflammatory disease of the airways (most commonly allergic), characterized by reversible bronchial obstruction with bronchial hyper-responsiveness  Hyper-responsive bronchi means constrict easily to a wide range of specific or nonspecific stimuli (triggers)  The triggers are too weak to affect non-asthmatics  Pathogenesis of bronchial asthma 9 Pathogenesis of bronchial asthma  Pathogenesis of bronchial asthma Frequent exposure to allergic stimuli causes infiltration of the bronchial wall by acute and chronic inflammatory cells. These cells release many inflammatory cytokines eg. histamine, adenosine, PGs, LTs, PAF, etc. Leading to:  Hypertrophy of airway smooth ms.  Attract and activate eosinophils, stimulate IgE production by B lymphocytes  Increased mucus secretion that is difficult to expel.  Congestion and edema of the respiratory mucosa.  Drugs causing bronchoconstriction in asthmatic 1-NSAIDs: e.g. aspirin. 2-Nonselective beta-blockers: e.g. propranolol. 3-Histamine and histamine releasers: eg. morphine and curare. 12  Aspirin induced asthma Cell membrane corticosteroids PLA2 NSAIDs Arachidonic acid Zeliotine Cox 5Lox PGs LTA4 PGE2 PGD2 PGF2 LTB4 LTC4 LTE4 LTR blockers LTD4 13  Lines of treatment of bronchial asthma Pathology of BA: TTT of BA: Bronchospasm Bronchodilation Airway inflammation Anti inflammation  Goals of therapy in patient with BA The goals is to achieve the best possible long term BA outcome: 1-Long term symptoms control, which include  Few/no asthma symptoms, quickly relieved  No sleep disturbance  Unimpaired physical activity 2-Long term asthma risk minimization, which include  No exacerbations  Improved or stable patient lung function  No requirement for maintenance oral corticosteroids 15  No medication side effects  Lines of treatment of bronchial asthma 1- Bronchodilators→ relieve of bronchial spasm a-β2 agonists b-Anti-muscarinic drugs. c-Methyl-xanthines. 2-Anti-inflammatory drugs→ Reduction of edema and congestion Corticosteroid 3-Adjuvant therapy: Leukotriene receptor antagonist 4-Biological therapy: According to the results of phenotyping 5-Others: a- Avoid drugs precipitating the attack. b-Desensitization or avoidance of antigen if it is known. c- Treatment of respiratory infection. d- O2 therapy e-Expectorants and mucolytic. f- Psychic support  Bronchodilators 1-β2 agonists 2-Anticholinergic drugs 3-Methylxanthines 17  1-Selective β2 agonists Short acting B2 agonist (SABA): Long acting B2 agonist(LABA): 1. Salbutamol (albuterol) 1. Formetrol. 2. Terbutaline. 2. Salmetrol. 3. Bambuterol. 4. Indacaterol. Long acting B2 agonist are chemical analogues of salbutamol but have a lipophilic side chain→ more affinity for the β2 receptors 18  1-Selective β2 agonists 19  1-Selective β2 agonists Mechanism of action of β2 agonists: Stimulate bronchial β2 receptors → ↑CAMP → 1-Bronchodilator 2-Decrease histamine release from mast cell 3-Improve mucociliary clearance 20  Adverse effects of beta2 agonists Adverse effects of beta2 agonists 1-Tachycardia and arrhythmia due to: Direct activation of cardiac β1 (due to loss of selectivity in high doses). Reflex from hypotension (caused by VD of skeletal ms BV). 2-Tolerance with prolonged use. 3-Tremors of skeletal Ms. 4-Hypokalemia (due to shift of K+ from blood to cells).  Adverse effects of beta2 agonists 5-SABA without ICS were associated with increase in asthma deaths  SABA treat symptoms but not disease  SABA fail to control the inflammatory component of asthma (predominantly eosinophilic)  Regular use of SABA even for 1-2 weeks is associated with ↑air way hyperresponsiveness& reduced bronchodilator effect (receptor down regulation)  Starting treatment with SABA train the patient to use it as their primary asthma treatment (poor adherence to inhaled corticosteroids)  There is strong evidence for more effective and safer alternative →as needed ICS-formoterol 22  Quiz 1 What is the most important mechanism of salbutamol in treatment of bronchial asthma? A. Inhibit phosphodiesterase enzyme B. Block adenosine receptor C. Inhibit phospholipase A2 D. Increase CAMP E. Block muscarinic receptor  2-Anti-muscarinic drugs Short acting muscarinic antagonist Long acting muscarinic antagonist (SAMA): (LAMA): Ipratropium bromide. 1. Glycopyrronium 2. Tiotropium 24  2-Anti-muscarinic drugs  Acetylcholine activate Gq coupled receptors → ↑ intracellular Ca →smooth muscle contraction  Anti-muscarinic drugs→ blocks M3 receptors in airway ms leading to→ bronchodilation.  M3 blockers is not sufficient alone for bronchodilatation must be combined with B2 agonists.  2-Anti-muscarinic drugs Selective M3 blockers is used but not atropine because:  They are more selective muscarinic blocker than atropine.  They can't cross BBB.  Do not cause excessive dryness of bronchial secretions. Adverse effects Dry mouth 26  3-Methylxanthines Classification: Natural: e.g. theophylline Semisynthetic: e.g. aminophylline.  Mechanism of action of methylxanthines agonist Meth. Gs AC PDE ATP cAMP AMP MLCK enzyme Contraction of S.M 28  Mechanism of action of methylxanthines Mechanism and pharmacological effects (2 main mech.) 1-Inhibition of phosphodiesterase enzyme (PDE3 and PDE4)→↑cAMP leading to:  Bronchodilator  Decrease histamine release from mast cell  Improve muco-ciliary clearance But ↑cAMP &cGMP leads also to the following :  ↑Cardiac contractility and arrhythmogenic action (PDE3). (adverse effect) 29  Mechanism of action of methylxanthines 2-Block of adenosine receptors (mech in ttt of BA) leading to :  Bronchodilatation (block bronchoconstrictor effect of adenosine)  ↓Mediator release from mast cells  But blocking adenosine receptor leads also to the following: (adverse effects)  CNS stimulation (block the inhibitory effect of adenosine on the CNS)  ↑ AV conduction (block the inhibitory effect of adenosine on AV conduction). 30  Adverse effects of methyl-xanthines 1-Narrow safety margin so be caution in renal and hepatic 2-Irritant: if given orally it causes gastritis, it is given after meals. 3-Rapid IV injection : tachycardia, arrhythmia, hypotension & syncope. 4-Tachycardia , palpitation, angina, arrhythmia. 5-Insomnia, anxiety, tremors & may be seizures ( CNS stimulation). 31  Quiz 2 Which of the following is one of the most important contraindication to the use of methylxanthines in treatment of bronchial asthma? A. Acute pulmonary edema. B. CNS depression. C. Arrhythmia D. Apnea of premature newborn E. Migraine  Summary and wrap up  Bronchial asthma is chronic inflammatory disease of the airways , characterized by reversible bronchial obstruction with bronchial hyper-responsiveness  These are many inflammatory cytokines released during BA, eg. histamine, adenosine, PGs, LTs, PAF etc  Lines of treatment of bronchial asthma include bronchodilators and anti-inflammatory drugs  Bronchodilators includes β2 agonists, anti-muscarinics &methylxanthines  β2 agonists is the most commonly used bronchodilator  Selective M3 blockers are more preferred than atropine but it cant be used alone.  Methylxanthine narrow safety margin inhibit of PDE4 enzyme and block adenosin receptors  References & recommended readings 1-What’s new in GINA 2024? GINA 2024 update published 22 May 2024 Download from ginasthma.org https://ginasthma.org/wp-content/uploads/2024/06/Whats-New-In-GINA-2024- WEBSITE.pptx 2-Brenner, C.S. G. Brenner and Stevens’ Pharmacology. [ClinicalKey Student]. Retrieved from: https://clinicalkeymeded.elsevier.com/#/books/9780323391665/ 3- Wecker, L. Brody's Human Pharmacology. [ClinicalKey Student]. Retrieved from https://clinicalkeymeded.elsevier.com/#/books/9780323476522/ thanks Fo r Wa tc hin g Dr. Ayat Abdelaziz 1. Hydatid disease Echinococcus granulosus 2. Amoebiasis Entamobae histolytica Dr. Ayat Abdelaziz Definition: it is the presence of hydatid cyst, larval stage of Echinococcus granulosus in the human tissues. The liver is the commonest organ affected (70%) followed by the lungs (20%), then the brain and other organs (10%).  Geographical distribution: cosmopolitan, more in cattle raising countries.  Morphology: 1. Adult: - Size: about 5 mm. - Scolex: globular with 4 suckers and double crown of hooks (similar to T. solium). - Strobila: composed of 3 segments, one immature, one mature and one gravid. - Mature segment: longer than broad. Reproductive organs as Taenia. - Gravid segment: is 1/2 length of the worm, longer than broad. The uterus develops lateral pouches which are full of eggs. 2. Egg: similar to T. solium - Size: 30-40 µ - Shape: spheroid. - Shell: thick radially striated embryophore - Colour: yellowish-brown. - Contents: hexacanth embryo (onchosphere) 3. Hydatid cyst: a complex cyst composed of daughter cyst inside and may be outside the mother cyst and contains several scolices. Unilocular hydatid cyst: it is the larval stage of E. granulosus. - Size: 1-10 cm. - Shape: spherical enclosed in a fibrous capsule produced by the host. - The wall of the cyst has 2 layers: (l) Outer laminated non-cellular layer. (2) Inner cellular germinal layer which secretes the laminated layer and produces scolices, brood capsules and daughter cysts. - Contents: (a) Individual scolices (microscopic). (b) Brood capsules: invagination of the germinal layer from which scolices develop. (c) Daughter cysts: cysts formed of the 2 layers of the mother cyst, giving rise to scolices, brood capsules and even grand daughter cysts. (d) Hydatid fluid. (e) Hydatid sand: detached scolices, brood capsules and daughter cysts that fall in the hydatid fluid are called hydatid sand. (f) Exogenous daughter cysts: a daughter cyst is produced outside the mother cyst by herniation through the fibrous capsule and may separate from it.  Life cycle: - Habitat: small intestine - DH: dogs or other carnivorous animals - IH: herbivorous animals (cattle) and occasionally man - Infective stage to dog: hydatid cyst - Infective stage to man: Eggs - Stages of life cycle: egg, onchosphere, hydatid cyst in (I. H.), adult in (D. H.). -Gravid segments and mature eggs pass in the faeces of definitive host. -When the egg is ingested by the intermediate host, the liberated onchosphere penetrates the intestinal wall into the blood stream to various parts of the body where it develops into a hydatid cyst, causing hydatid disease.  Mode of human infection: ingestion of eggs of Echinococcus species by the following ways: 1- Ingestion of water or vegetable polluted by infected dog's faeces. 2- Handling infected dogs where hair is usually contaminated with eggs. 3- Man is infected with the alveolar cyst during the skinning of foxes to make furs or from collecting strawberries polluted with fox's faeces.  Pathogenicity and clinical picture: depend on the size of the cyst and the organ affected. 1- Hepatic hydatid cyst: indigestion, jaundice and discomfort in the right hypochondrium. 2- Pulmonary hydatid cyst: dyspnea, cough, chest pain and haemoptysis. 3- Cerebral hydatid cyst: symptoms of increased intracranial tension and epilepsy. 4- Osseous hydatid cyst: erosion and spontaneous pathological fracture of long bones. 5- Rupture of the cyst results in anaphylactic shock and transplantation of the germinal layer in other tissues producing secondary cysts.  Diagnosis: I. Clinical diagnosis: - History of contact with dogs. - Slowly growing cyst (space occupying and pressure effects) with hydatid thrill in case of large abdominal cyst. II. Laboratory diagnosis: A- Direct: - Puncture and aspiration to demonstrate hydatid cyst (may lead to leakage of fluid and the risk of anaphylactic shock). - Radiological: X-ray, ultrasonography (U.S.), C.T. scans. - Blood examination reveals eosinophilia in 20-25% of cases. B- Indirect: -Intradermal allergic test (Casoni test): 0.2 ml of sterile hydatid fluid is injected intradermally. In positive cases an erythematous wheel is formed within 20 min and a delayed reaction appears after 24 hours. -Serological methods: using hydatid fluid antigen for detection of antibodies by: 1. Precipitin reaction: equal parts of hydatid fluid and patient's serum incubated at 37°C for 1 hour show flocculation in 36 hours. 2. ELISA, IHA, CFT, IFA  Treatment: 1- Surgical treatment: is recommended for unilocular cysts in accessible sites with pre-operative administration of Mebendazole. 2- Sterilization: some of hydatid fluid is replaced by 10% formalin for 5 minutes then the content is aspirated and repeatedly washed with saline or ethanol to kill the germinal layer and scolices causing cyst collapse. 3- Medical treatment: when surgical interference is impossible or contraindicated, Mebendazole can be used in high dose and for a long period (about 3 months up to one year), as the drug stop proliferation and spread of the cysts.  Prevention and control: 1. Hydatid cysts found in slaughtered animals should be destroyed and not fed to dogs. 2. Stray dogs should be destroyed. 3. Pet dogs should be examined and dewormed periodically. 4. Avoid close contact and playing with dogs. 5. Avoid contamination of hands, food and drink with dog's faeces.  Geographical distribution: Worldwide distribution especially in tropical areas and poor communities.  Morphology: 1. Trophozoite (Vegetative or growing stage): - Size: 10-60 µ (average 20 µ). - Shape: Irregular outline with finger like pseudopodia and active movement. - Cytoplasm: It is formed of outer clear hyaline, refractile ectoplasm and inner granular endoplasm containing nucleus, food vacuoles, erythrocytes (RBCs), occasionally bacteria, and tissue debris. - Nucleus: It has centrally located fine karyosome and peripheral chromatin dots arranged regularly at the inner side of the nuclear membrane. 2. Cyst: - Size: 10-15 µ in diameter. - Shape: It is rounded, - Wall: Has smooth refractile cyst wall. - Content: The early cyst contains glycogen vacuoles and 1-4 chromatoid bodies which are sausage-shaped with rounded ends. They are formed of RNA & DNA, and represent stored proteins which are consumed with repeated nuclear division. - Immature cysts may be mono- or bi-nucleated. - Mature cysts contain 4 nuclei formed by mitotic division. - Nuclei are similar to that of the vegetative form.  Life cycle: - Habitat: a. Trophozoite: Inhabits the wall and lumen of the large intestine, with extra-intestinal metastases (liver, lung and brain, etc.). b. Cyst: Inhabits the lumen of the large intestine. - DH: Man - IH: No - RH: Dogs, rats and monkeys. - Infective stage: Mature quadrinucleated cyst - Stages of life cycle: Trophozoite and cyst  Mode of human infection: 1. Ingestion of mature quadrinucleated E. histolytica cysts in contaminated food or drink, or through infected food handlers. 2. Mechanical transmission by flies and cockroaches. 3. Autoinfection: feco-oral route (hand to mouth contact). - Trophozoite may invade the wall of large intestine by their lytic secretion to invade the host tissues through blood vessels (extra-intestinal invasion).  Pathogenicity: - Entamoeba trophozoites attach themselves to the surface epithelium aided by an enzyme called E. histolytica lectin and start crawling over the mucosa. -Trophozoites secrete cytolytic enzymes; haemolysins and pore-forming enzymes (amoeba pore), which lead to necrosis of epithelial cells with pore formation. - Tophozoites enter to the submucosa through the hole formed in the epithelial layer and continue the process of cytolysis downwards and laterally. - The lesion is flask shaped or crater like ulcer containing cytolysed cells, mucus and amoeba trophozoites, while amoeba cysts never found in tissues. - Ulcers are more common in the ileocaecal region followed by the sigmoid- rectal region. - Ulcer expansion can penetrate the intestinal wall →intestinal perforation with hemorrhage and peritonitis. - Invasion of blood vessels may lead to spread of amoebae causing extra intestinal amoebiasis. Pulmonary amoebiasis: - It usually results from direct extension from the liver across the diaphragm but may be also haematogenous. - Lung abscess may be single or multiple, in the lower lobe of right lung.  Clinical picture Pulmonary amoebiasis: - It is characterized by chest pain, cough, dyspnea, chills, fever and leukocytosis. - Hepatobronchial fistula is usually associated with expectoration of chocolate brown sputum.  Diagnosis: 1. Microscopic examination: - For detection of trophozoites in: a. Aspirated pus or biopsy from amoebic liver or lung abscess. b. Sputum in pulmonary amoebiasis. c. CSF in cerebral amoebiasis. - Stool samples are not of much value as cyst can be detected in less than 15% of hepatic ameobiasis. 2. Serodiagnosis: The circulating amoebic antigens or antibodies can detected by IHA, IFA or ELISA. 3. Radiological examination: Amoebic liver, lung or brain abscesses can be diagnosed by ultra-sonography (US), CT or MRI.  Treatment: 1. Luminal amoebicides: They act in the intestinal lumen. -Diloxanide fluorate (Furamide). - Metronidazole (Flagyl). - Tinidazole (Fasigen). - Paromomycin. - Iodoquinol. 2. Tissue amoebicides: They act against the tissue invasive form. a. Amoebicides acting on all types of tissues: - Metronidazole. -Tinidazole. - Emetine hydrochloride.  Prevention and control: 1. Environmental sanitation as: Anti-fly measures, proper sewage disposal, safe water supply and avoid using excreta as fertilizer. 2. Health education for: Washing green vegetables, fruits and hands before eating. 3. Treatment of cases, especially carriers Bacterial Infections of Lower Respiratory Tract  Instructors information Contact Official email Prof. Niveen Adel Mohamed El-wakeel [email protected] Dr. Amany Elmatbouly Elsayed [email protected] Dr. Aya Ahmad Elnegery [email protected] Dr. Aya Mahmoud Fathy [email protected] Dr. Amira Yahia Mohamad [email protected] Dr. Nada Hamid Qandeel [email protected] Dr. Lames Taha Mohamad [email protected]  Learning outcomes By the end of this lecture the students will be able to: 1. Designate common bacterial causes of Bronchitis and pneumonia. 2. Detect the characters of pneumococci, pathogenesis and laboratory diagnosis of pneumococcal pneumonia. 3. Label the characteristics and laboratory diagnosis of bacteria causing atypical pneumonia. 4. Enumerate causes of empyema.  Lecture Outline ▪ Causative agents of bronchitis and pneumonia. ▪ Laboratory diagnosis of pneumococcal pneumonia. ▪ Bacterial causes and diagnosis of atypical pneumonia. ▪ Causes of empyema.  Case scenario, Clinical Correlate, Practice points A 52-year-old woman who was diagnosed with acute leukemia and was scheduled to receive chemotherapy. Because this chemotherapy usually leads to severe myelosuppression, she received prophylactic levofloxacin , amphotericin B , and trimethoprim-sulfamethoxazole. On day 10 after chemotherapy, she developed neutropenic fever 39°C. Cultures of urine and 3 sets of blood cultures obtained at fever onset were negative. The physical examination and a chest radiograph revealed no abnormal findings. Cytotoxic chemotherapy and prophylactic antibiotics were discontinued, and the patient was started on broad- spectrum antibiotic therapy with piperacillin and tazobactam. Repeated blood cultures did not yield any organisms, The patient remained febrile, and an increase in respirations (22/min) was noted, but a chest radiograph was normal. A bronchoscopy was performed, and a bronchoalveolar lavage (BAL) specimen was examined for various pathogens. Culture on On McCoy cells, after incubation, typical cytoplasmic inclusion bodies are seen. Inclusion bodies are detected by staining with Giemsa or iodine. What is your probable diagnosis? Mention a diagnostic confirmative test for this patient? What is the proper treatment?  Causes of Bronchitis Respiratory viruses Bacterial (Most common) (less common) ▪ Mycoplasma pneumoniae, ▪ Chlamydia pneumoniae ▪ Bordetella pertussis, ▪ B. parapertussis, ▪ Haemophilus influenzae. Pneumonia: Definition: Infection and inflammation of the lungs.  Classification A Community acquired B pneumonia: pneumonia presenting within the Typical: High fever, productive cough, community, or within 48 h of diffuse lobar or patchy infiltrates. hospital admission. Atypical: Hospital acquired Low fever, dry cough, diffuse pneumonia: pneumonia ground glass infiltrates. presenting >48 h after admission to hospital  Community acquired pneumonia Hospital acquired pneumonia Adults: Most common: ▪ S. pneumoniae Gram-negative bacilli (eg P. Less common: aeruginosa, K. pneumonia) ▪ M. pneumoniae S. aureus ▪ H. influenzae S. pneumoniae ▪ C. pneumoniae H. influenzae ▪ Respiratory viruses. Legionella spp. Children: Most common: ▪ Respiratory viruses ▪ M. pneumoniae Less common: ▪ S. pneumoniae ▪ H. influenzae ▪ S. aureus ▪ Group B Streptococcus (neonates)  NB Nosocomial pathogens are likely to be resistant to multiple antimicrobial agents.  Typical pneumonia Acute lobar pneumonia Bronchopneumonia ▪ Streptococcus pneumoniae, ▪ Staphylococcus aureus, ▪ Staphylococcus aureus, ▪ Klebsiella pneumoniae, ▪ Klebsiella pneumoniae, ▪ Pseudomonas, ▪ Streptococcus pyogenes. ▪ Streptococcus pneumoniae, Streptococcus pyogenes.  Streptococcal pneumoniae Morphology: ▪ Gram positive lancet shaped diplococi. ▪ Non spore forming, non motile, capsulated.  Virulence factors Polysaccharide S. pneumoniae can be capsule classified into 80 serotypes according to Is the main virulence antigenic structure of factor as it resists the capsule. phagocytosis  Diseases caused by S. pneumoniae 1. The most frequent cause of pneumonia & its complications as; Meningitis, Bacteremia And endocarditis. 2. It is common cause of sinusitis, acute bacterial otitis media & conjunctivitis. Diagnosis: 1. Sample collection sputum which is rusty. 2. Direct film with Gram Detect morphology 3. Culture Culture Culture condition media  Culture condition Culture media ▪ Facultative anaerobe. ▪ No growth on ordinary media. ▪ Optimum temperature is 37 ֗C. ▪ On blood agar produce alpha hemolysis, ▪ Can grow on normal co2, but 5-10% colonies are small with depressed enhance growth. centers. Alpha hemolysis  4. BR Fermentation of inulin, Bile solubility, Optochin sensitive Sensitivity to Optochin. 5. Pathogenicity to mice Intra peritoneal injection of culture in mice causes death in 18-48 hours due to septicemia.  6. Capsular swelling reaction Capsule can be detected by a serological test (Quelling reaction). When the specific polyvalent antibodies are added to bacterial suspension → causes swelling of the capsule (Capsular swelling reaction). Vaccine is available Vaccine – contains purified capsular material from 23 of most common serotype causing pneumococcal infections, Recommended for young children, elderly, debilitated or immunosuppressed individuals.  Answer Which is of the following is the main virulence factor of Streptococcus pneumonie? a. Staphylokinase. b. Polysaccharide capsule c. Protein A d. M protein. e. Coagulase  Atypical pneumonia  Atypical pneumonia 01 03 Mycoplasma Chlamydia pneumoniae pneumoniae 02 04 Legionella Chlamydia psittaci pneumophila 01 Mycoplasma pneumoniae Distinguishing Features: ▪ No cell wall (not seen Extracellular, on Gram-stained Very small organisms, smear). Pleomorphic. Membrane with cholesterol but does Clinical manifestation: not synthesize ▪ Pharyngitis. cholesterol, ▪ Bronchitis. Requires cholesterol ▪ Primary atypical pneumonia. for in vitro culture.  —Pathogenesis ▪ Attaches to respiratory epithelium via P1 protein ▪ Inhibits ciliary action. ▪ Produces hydrogen peroxide, superoxide radicals, and cytolytic enzymes. Damage the respiratory epithelium, leading to necrosis.  Diagnosis 01 02 03 Specimen Culture ▪ Sputum. Microscopic examination ▪ Throat swab. On enriched fluid media or special ▪ Nasopharyngeal ▪ They are highly mycoplasma agar, fried-egg shaped colonies secretions. pleomorphic, may be after several days of incubation. spherical to long filamentous. Colonies can be identified - by staining directly on ▪ Do not stain by Gram agar with fluorescein-conjugated antibody or by stain. demonstrating growth inhibition on adding specific antiserum. Fried-egg shaped colonies  Diagnosis 04 05 Sero-diagnosis Molecular Main method DNA probes and PCR Treatment for M. pneumoniae infection; Erythromycin, azithromycin, and clarithromycin. ▪ No cephalosporins or penicillins. Answer True about Mycoplasma pneumoniae: a. Cytoplasmic membrane does not contain sterol b. Grow on nutrient agar. c. Has cell wall d. Resistant to erythromycin e. Fried egg colonies  Legionella Morphology Mode of transmission: Legionella pneumophila ▪ Inhalation of aerosolized mist Source of infection pleomorphic Gram from contaminated water negative bacilli, ▪ Water, particularly source. motile, non sporing. the surface waters of rivers and lakes. ▪ Disease may occur in the community or in hospitals ▪ Air-conditioning water (through aspiration, cooling tanks. contaminated water, or respiratory equipment ). ▪ No person-to-person transmission.  Virulence factors Endotoxin Facultative intracellular Disease(s) Legionnaires disease Pontiac fever Acute atypical pneumonia Influenza-like illness Sporadically or in outbreaks  Diagnosis 1. Specimen 2. Microscopic Examination Sputum, pleural fluid, trans tracheal ▪ Gram stain of specimen showing aspirations and bronchoalveolar intracellular and extracellular lavage. Legionella ▪ Direct detection of bacterial antigen in clinical specimens: By direct immunofluorescence.  Diagnosis 3. Culture 4. Serologic diagnosis ▪ Strict aerobic. ▪ Detection of specific antibodies ▪ The medium of choice is buffered (IgM and IgG) in serum. charcoal-yeast extract (BCYE) medium. ▪ The bacteria produce small colonies after 3–5 days. Treatment Fluoroquinolone or Azithromycin or erythromycin Legionella on BCYE media Chlamydia  General character Chlamydia differ from virus ▪ Obligate intracellular 1. They contain both DNA and RNA. bacteria, ▪ Elementary body/reticulate 2. They have Gram negative cell body, wall. ▪ Not seen on Gram stain, 3. They contain prokaryotic ▪ Cannot make ATP. ribosomes. 4. They multiply by binary fission. 5. They are susceptible to many antibiotic. Important species: 1. C. trachomatis. 2. C. psittaci. 3. C. pneumoniae.  Diseases caused by Chlamydia Chlamydia Chlamydia Chlamydia trachomatis pneumoniae psittaci ▪ Pneumonia Psittacosis Nongonococcal urethritis. Trachoma. ▪ Bronchitis Inclusion conjunctivitis of the newborn. ▪ pharyngitis Pneumonia of newborns. Lymphogranuloma venereum.  Elementary body (EB) Reticulate body (RB) Small Large Extracellular Intracytoplasmic Infectious form Noninfectious form Non-replicating Metabolically active and replicating Released from ruptured Within the cell (site of infected cell. replication) appear as inclusion bodies and visualized microscopically. Diagnosis: 1. Sample collection Sputum, scrapings from eyes or the urogenital tract. 2. Microscopic examination Inclusion bodies are detected 3. Culture by staining with Giemsa or On McCoy cells, after iodine. incubation, typical cytoplasmic inclusions bodies are seen. Staining with fluorescent C pneumoniae grows better in monoclonal antibodies. HEp-2 cells.  4. Serological tests 5. Molecular techniques: Detection of chlamydial antigen directly ▪ DNA probes: to diagnose C. in specimens by using specific trachomatis in tissue Immunoflurescent antibodies. specimens. Detection of anti-Chlamydia antibodies. ▪ Polymerase chain reaction (PCR). Answer The elementary body of chlamydia is characterized by: a. Large b. Extracellular c. Non infectious d. Metabolically active replicating e. Replicating Empyema Definition: Collection of purulent fluid in an existing body cavity, especially the pleural space between the lung and the chest wall.  Causes of empyema Community acquired: Nosocomial: S. Aureus S. pneumoniae Gram-negative bacilli Streptococcus pyogenes Anaerobes Anaerobes  Case scenario, Clinical Correlate, Practice points A 52-year-old woman who was diagnosed with acute leukemia and was scheduled to receive chemotherapy. Because this chemotherapy usually leads to severe myelosuppression, she received prophylactic levofloxacin , amphotericin B , and trimethoprim-sulfamethoxazole. On day 10 after chemotherapy, she developed neutropenic fever 39°C. Cultures of urine and 3 sets of blood cultures obtained at fever onset were negative. The physical examination and a chest radiograph revealed no abnormal findings. Cytotoxic chemotherapy and prophylactic antibiotics were discontinued, and the patient was started on broad- spectrum antibiotic therapy with piperacillin and tazobactam. Repeated blood cultures did not yield any organisms, The patient remained febrile, and an increase in respirations (22/min) was noted, but a chest radiograph was normal. A bronchoscopy was performed, and a bronchoalveolar lavage (BAL) specimen was examined for various pathogens. Culture on On McCoy cells, after incubation, typical cytoplasmic inclusion bodies are seen. Inclusion bodies are detected by staining with Giemsa or iodine. What is your probable diagnosis? Mention a diagnostic confirmative test for this patient? What is the proper treatment?  References ▪ Brooks, G. F., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2013). Jawetz, Melnick, & Adelberg's medical microbiology. New York: McGraw Hill Medical. ▪ Topley and Wilson’s Microbiology and Microbial Infections: 10th edition. 51 THANKS Upper Respiratory Tract Infections Instructors information Contact Official email Prof. Niveen Adel Mohamed El-wakeel [email protected] Dr. Amany Elmatbouly Elsayed [email protected] Dr. Aya Ahmad Elnegery [email protected] Dr. Aya Mahmoud Fathy [email protected] Dr. Amira Yahia Mohamad [email protected] Dr. Nada Hamid Qandeel [email protected] Dr. Lames Taha Mohamad [email protected]  Learning outcomes By the end of this lecture the students will be able to: 1. Label the normal microbiota of the respiratory tract. 2. Define common infections and the most common organisms causing various upper respiratory tract infections. 3. Deliberate the characteristics, transmission of Corynebacterium diphtheriae and the effect of diphtheria toxin. 4. Designate the characteristics and laboratory diagnosis Bordetella pertussis. 5. Describe the characteristics and laboratory diagnosis of Haemophilus influenzae.  Lecture Outline 01 04 Normal microbiota of the Pertussis. respiratory tract 02 05 Types of upper respiratory Diphtheria. tract infections. 03 06 Causative organisms of upper Haemophilus influenzae. respiratory tract infections  Case scenario, Clinical Correlate, Practice points, A 12-year-old male child was brought to the emergency department with chief complaints of acute onset of fever, productive cough, and dyspnea with odynophagia for 5, 3, and 2 days, respectively. His parents revealed that the pattern of fever had changed from low grade and intermittent to high grade and continuous in the preceding 5 days. He was finding it extremely difficult to swallow both solids and liquids of late and had labored noisy breathing. His voice had also changed with slight hoarseness in character for 2 days. The child was repeatedly coughing and expectorating yellow-colored, non-foul-smelling, non-blood-stained sputum. As per the information given by his mother, the immunization status of this child was inappropriate for age. General physical examination revealed that the child was conscious and oriented but looked toxic. He was febrile with a temperature of 40.5°C, Inspiratory stridor was also present. No other abnormality was detected on systemic examination. Oropharyngeal examination revealed that the soft palate was congested with poor oro-dental hygiene. There were grayish-white membranous patches on the medial aspect of both the tonsils and posterior pharyngeal wall were congested and edematous. What is your probable diagnosis? Mention what you will do very rapidly for this child?  Normal microbiota of the respiratory tract Nose: ▪ Staphylococcus epidermidis, ▪ Diphtheroids. Pharynx: ▪ Haemophilus, ▪ Pneumococci, ▪ Mycoplasma. Types of upper Symptoms of URIs can respiratory tract include: infections? ▪ Cough, sore throat, Typical infections of the ▪ Runny nose, nasal congestion, upper respiratory tract sneezing, include: ▪ Headache, low grade fever. ▪ Tonsillitis, ▪ Pharyngitis, ▪ Laryngitis, ▪ Sinusitis, ▪ Otitis media. Causative Organisms of Upper Respiratory Tract Infections OTITIS MEDIA Causative organisms: 1. Staphylococcus aureus, 2. Streptococcus pneumoniae, 3. Streptococcus pyogenes, 4. Klebsiella pneumoniae, 5. Haemophilus influenza, 6. Pseudomonas aeruginosa. 7. Proteus and anaerobic bacteria, 8. Fungal infection may occur.  NB: The organisms reach the middle ear from nose or throat via the Eustachian tube. Diagnosis: 04 BR 01 According to each organism. Identification Sample Of isolated swabs are taken colonies Culture from discharge. Blood agar and nutrient agar plates (at 37°c for 24 03 hours). 02 Sore throat Causative organisms: 01 03 Acute follicular tonsillitis: Candida albicans infection. Is caused by Streptococcus pyogenes, Staphylococcus aureus and Streptococcus viridans. 02 04 Diphtheria. Herpes febrilis virus 1. C. diphtheriae, 2. Streptococcus pyogenes.  Diphtheria Corynebacterium diphtheria Morphology: ▪ Gram positive bacilli, Non motile, non capsulated, non sporulated. ▪ Beaded appearance due to presence of metachromatic granules which can be seen by Neisser stain (the granules are blue & the bacilli are brown). ▪ Characteristic Chinese letters arrangement.  Diphtheria toxin ▪ Polypeptide toxin. ▪ Toxigenic strains are lysogenic (infected by temperate phage, that carry the gene for diphtheria toxin) ▪ Non lysogenic strains are avirulent. ▪ Toxin inhibits protein synthesis in eukaryotic cell leading to cell death. ▪ Cause degenerative changes in heart muscle, nerve, kidney and liver.  Diphtheria ▪ Characterized by sore throat, low grade fever, & an adherent membrane on tonsil(s), pharynx, and/or nose, bulky neck. ▪ Source: case or carrier. ▪ Transmitted by direct or indirect droplet infection. Prevention & Control of diphtheria 1. Active immunization 2. Passive immunization ▪ With diphtheria toxoid. ▪ By diphtheria antitoxin. ▪ Toxoid is given in 2,4,6 months then booster dose at 1 year later and at the ▪ Given to children in contact entrance to elementary school. with a case of diphtheria. ▪ Usually, infants are immunized with a trivalent (DPT vaccine) containing diphtheria toxoid, pertussis vaccine, & tetanus toxoid.  Treatment of diphtheria 1. Antitoxin 2. Chemotherapeutic Should be given Penicillin, erythromycin are immediately if diphtheria is drugs of choice. suspected clinically. The following is a morphological character of Corynebacterium diphtheria: a. Motile with peritrichate flagellae. b. Capsulated. c. Not stained by gram stain. d. By Neisser stain granules are brown and bacilli are blue. e. Beaded in appearance  Whooping cough (Genus Bordetella) Bordetella Bordetella pertussis Bordetella para- pertussis bronchiseptica Cause whooping cough (pertussis). Morphology: ▪ Small Gram-negative coccobacillus with bipolar staining, ▪ Non motile, ▪ Capsulated, ▪ Non sporulated.  1. Invasive adenylate cyclase Genus Bordetella (hemolysin). Virulence factors 2. Lethal toxin: causes inflammation and local necrosis. Adherence mechanisms of B. Toxins Produced 3. Tracheal pertussis. cytotoxin: destroys the ciliated cells of Endotoxin trachea. Exotoxin 4. Pertussis toxin: which enters target cells and increase intracellular levels of CAMP Whooping cough  Whooping cough Pathogenesis: ▪ B. pertussis is strict human pathogen, not present in normal human flora. ▪ Pertussis is a common and dangerous childhood disease in unvaccinated populations. ▪ Transmission is by: - Inhalation of droplets expelled in cough spray. - Contaminated objects. Incubation period: 1 - 2 weeks. 1. Catarrhal phase The disease pertussis has two stages 2. Paroxysmal phase  1. Catarrhal phase 2. Paroxysmal phase (colonization): (toxemic): ▪ Lasts 1 - 2 weeks. ▪ Lasting 2 – 4 weeks. ▪ Characterized by ▪ Toxins cause injury of fever, malaise, ciliated cells. rhinitis, and cough. ▪ Characterized by ▪ The patient is highly paroxysmal coughing infectious. that often ends in a characteristic inspiratory gasp (whoop).  Diagnosis Nasopharyngeal swabs or nasopharyngeal secretions. Specimens Direct film Culture Identification of Direct fluorescent antibody isolated colonies test to detect B. pertussis in nasopharyngeal specimens. - Gram stained film. Culture condition Culture media - BR. Strict aerobe - Slowly growing, need - Slide agglutination incubation for 3-7 with specific antisera. days. - Nutritionally fastidious  Diagnosis PCR Serological tests Detection of B. pertussis DNA by PCR has been described. The detection of specific IgA and IgM antibodies, however, is indicative of recent infection.  Culture media for B. pertussis: BR for B. pertussis: ▪ No growth on common laboratory ▪ Oxidase positive. media. ▪ Urease negative. ▪ Need rich media supplemented with blood. ▪ The widely used medium is Bordet- Gengou agar (containing blood, potato extract and glycerol) or charcoal-horse blood agar (Regan- Lowe). ▪ Colonies are glistening with appearance of bisected pearl and narrow zone of haemolysis around.  Prevention: 1. A killed whole bacterial vaccine is administered as DPT combination. 2. Acellular pertussis vaccines containing purified proteins have been developed. The following is TRUE about Bordetella pertussis: a. Grows on Bordet-Gengou medium. b. Grows on common laboratory media. c. Require X and V factors for growth. d. Oxidase negative. e. Urease positive.  Genus Haemophilus ▪ Gram-negative coccobacillus. ▪ Requires certain growth factors present in blood (haemophilic) for their growth.  Important species are: 01 02 H. influenzae. H. parainfluenzae. 03 04 H. aegyptius. H. ducreyi.  Haemophilus Influenzae Classified into: Only 3-7% of Encapsulated or healthy Carrier: typable strains Non- individuals Pharyngeal (have encapsulated are carriage of Hib is intermittently polysaccharide present in important in the capsule). harbor H. nasopharynx of influenzae type b transmission of Non- 75% of healthy (Hib) in the the bacterium. encapsulated or non-typable people. upper respiratory strains (if they tract. lack a capsule).  Morphology: Culture Characters: ▪ Gram negative coccobacilli, ▪ Facultative anaerobes, ▪ Non motile, ▪ Require 5% CO2, ▪ Non sporulated, ▪ No growth on ordinary media. ▪ Capsulated. ▪ Need two growth factors for growth (V & X).  NAD+ (factor V) Is released into the medium by red blood cells and is available in blood agar. Hemin (factor X) Is bound to red blood cells and is not released into the medium unless the cells are broken up, as in chocolate agar. H. influenzae requires both factors X and V so it grows on chocolate agar but NOT on blood agar. ▪ It can grow on a blood agar as small colonies called satellite colonies around colonies of other bacteria that can lyse red blood cells as S. aureus. ▪ Staphylococci can produce V factor required for H. influenzae. Other Haemophilus species require only NAD+ and can grow on blood agar. Virulence factors The most important 1. Capsule virulence factor as it resists phagocytosis. For adhesion. 2. Fimbriae 3. Endotoxin evasion of immunity. 4. IgA protease  Disease produced: Typable Nontypable Type b H. influenzae is the Nontypable H. influenzae can most virulent organism of cause: Haemophilus species causing: ▪ Localized infections as otitis ▪ Blood stream invasion. media, ▪ Meningitis in children ▪ Sinusitis, younger than 2 years. ▪ Tracheobronchitis, ▪ Epiglottitis. ▪ Pneumonia in infants, ▪ Bacteremia. children, and adults. ▪ And cellulites.  Haemophilus Diagnosis Specimen Direct fim Culture Sputum, Pus, C.S.F. To show morphology. Previous discussed Treatment Penicillin & Cephalosporins Haemophilus influenza do not grow on blood agar because: a. NAD+ is not available in blood agar. b. NAD+ is not released into blood agar by red blood cells c. Hemin is not bound to red blood cells. d. blood contains inhibitory compounds. e. Hemin is released only when RBCs are broken.  Case scenario, Clinical Correlate, Practice points, A 12-year-old male child was brought to the emergency department with chief complaints of acute onset of fever, productive cough, and dyspnea with odynophagia for 5, 3, and 2 days, respectively. His parents revealed that the pattern of fever had changed from low grade and intermittent to high grade and continuous in the preceding 5 days. He was finding it extremely difficult to swallow both solids and liquids of late and had labored noisy breathing. His voice had also changed with slight hoarseness in character for 2 days. The child was repeatedly coughing and expectorating yellow-colored, non-foul-smelling, non-blood-stained sputum. As per the information given by his mother, the immunization status of this child was inappropriate for age. General physical examination revealed that the child was conscious and oriented but looked toxic. He was febrile with a temperature of 40.5°C, Inspiratory stridor was also present. No other abnormality was detected on systemic examination. Oropharyngeal examination revealed that the soft palate was congested with poor oro-dental hygiene. There were grayish-white membranous patches on the medial aspect of both the tonsils and posterior pharyngeal wall were congested and edematous. What is your probable diagnosis? Mention a what you will do very rapidly for this child?  References ▪ Brooks, G. F., Jawetz, E., Melnick, J. L., & Adelberg, E. A. (2013). Jawetz, Melnick, & Adelberg's medical microbiology. New York: McGraw Hill Medical. ▪ Topley and Wilson’s Microbiology and Microbial Infections: 10th edition. 48  Thanks Any question? Intercostal nerves & Diaphragm Department of human Anatomy and Embryology Faculty of Medicine Mansoura National University, Egypt  Intended Learning Outcomes (ILOs) 1. Identify the components of the Thoracic Wall. 2. Name the boundaries and structures passing through the thoracic inlet. 3. Name the boundaries and structures passing through the thoracic outlet. 4. Recognize the origin, insertion, nerve supply, extent, direction of fibers and action of intercostal muscles. 5. Mention the mechanism of respiration. 6. Identify the origin, features and branches of intercostal nerves 7. Recognize the origin, branches and termination of intercostal arteries 8. Recognize the origin, tributaries and termination of intercostal veins  Agenda 1. What are the components of the Thoracic Wall. 2. What are the boundaries and structures passing through the thoracic inlet? 3. What are the boundaries and structures passing through the thoracic outlet? 4. What is the origin, insertion, nerve supply, extent, direction of fibers and action of intercostal muscles? 5. What is the mechanism of respiration? 6. What is the origin, features and branches of intercostal nerves? 7. What is the origin, branches and termination of intercostal arteries? 8. What is the origin, tributaries and termination of intercostal veins?  Intercostal Nerves Definition: they are the ventral rami of the thoracic spinal nerves. Number: 11 nerves on each side. (The 12th is called Subcostal nerve) Types: 1. Typical: supply only the thoracic wall. They are the 3rd – 6th nerves. 2. Atypical: supply parts outside the thoracic wall. They are the 1st, 2nd, 7th – 11th The 1st joins the brachial plexus and supplies the upper limb The 2nd has a lateral cutaneous branch called intercostobrachial, which supplies the skin of the axilla 7th-11th (thoraco-abdominal) & 12th (subcostal): Supply the Anterior Abdominal wall Source: https://www.google.com.eg/url?sa=i&url=https%3A%2F%2Fwww.jaypeedigital.com%2FeReader%2Fchapter%2F9788184484618%2Fch17&psig=AOvVaw1 v9JQbexC RX2SnrHppnO9n&ust=1729564445166000&source=images&cd=vfe&opi=89978449&ved=0CBcQjhxqFwoTCOiuoum3nokDFQAAAAAdAAAAABAR  Intercostal Nerves Typical intercostal nerves Number: they are the 3rd – 6th intercostal nerves. Course and relations: At the posterior part of the intercostal space: it passes between the parietal pleura and posterior intercostal membrane. At the angle of the rib: it passes between the internal intercostal and innermost intercostal muscles. It passes in the intercostal groove below the intercostal vessels (VAN from above downwards). At the costo-chondral junction: passes between the internal intercostal muscle and the parietal pleura. Passes in front of the Sternocostalis muscle and internal thoracic artery. 1 cm lateral to the sternum: it pierces the internal intercostal muscle, anterior intercostal membrane and pectoralis major to become anterior cutaneous nerve.  Intercostal Nerves Branches: 1) Communicating branches to the sympathetic chain: they are: Preganglionic branch: myelinated (white ramus). Postganglionic branch: non-myelinated (gray ramus) 2) Muscular branches: to the intercostal muscles. 3) Pleural Branch: To the parietal pleura 4) Collateral branch: runs on the upper border of the rib below to supply the intercostal muscles. 5) Lateral cutaneous branch: Arises at the angle of the rib. Pierces the internal intercostal, external intercostal and serratus anterior muscle. Divides into anterior and posterior branches. Supplies the skin of the lateral part of the thoracic wall. 6) Anterior cutaneous branch: Divides into medial and lateral branches. Supplies the skin of the front of the thoracic wall. https://www.google.com.eg/url?sa=i&url=https%3A%2F%2Fmobilephysiotherapyclinic.in%2Fintercostal-nerves%2F&psig=AOvVaw2mWKb6TnNi4lQCP- Aj2UYi&ust=1729564838038000&source=images&cd=vfe&opi=89978449&ved=0CBcQjhxqFwoTCPDOlKO5nokDFQAAAAAdAAAAABAE  Diaphragm Definition: it is the musculofibrous partition which separates the thoracic cavity from the abdominal cavity. Origin: Sternal: back of xiphoid process. Costal: inner surface of the lower 6 costal cartilages. Vertebral: 2 crura and 5 arcuate ligaments 2 crura: Right crus & Left crus 5 Arcuate ligaments: Median Arcuate ligament. 2 Medial Arcuate ligaments. 2 Lateral Arcuate ligaments. https://www.google.com.eg/url?sa=i&url=https%3A%2F%2Fwww.slides hare.net%2Fslideshow%2Fanatomy-of- diaphragm%2F227000633&psig=AOvVaw0NgdDgqb1x_oq9iWVyVxGy& ust=1729565560900000&source=images&cd=vfe&opi=89978449&ved= 0CBcQjhxqFwoTCID1q_u7nokDFQAAAAAdAAAAABAE Insertion: central tendon of diaphragm, which is U-shaped with its concavity directed backwards. It is formed of 3 lobes (leaflets). (central, the right copula & left copula) Nerve supply: phrenic nerve and lower 6 thoracic nerves. Actions: chief muscle of inspiration. https://en.wikipedia.org/wiki/Thoracic_diaphragm#/media/File:1113_The_Diaphragm.jpg https://www.google.com.eg/url?sa=i&url=https%3A%2F%2Fwww.amboss.com%2Fus%2Fknowledge%2Fthoracic-cavity&psig=AOvVaw1uRB- zc8yUV6Ec9Hrtk8Bi&ust=1729566168304000&source=images&cd=vfe&opi=89978449&ved=0CBcQjhxqFwoTCOCq36C-nokDFQAAAAAdAAAAABAw Relations: ❑ Upper surface: Right copula: right lung and pleura. Left copula: left lung and pleura. Central tendon: pericardium and heart. ❑ Lower surface: Right copula: right lobe of the liver, right kidney and right suprarenal gland. Left copula: left lobe of the liver, left kidney, left suprarenal gland, spleen and fundus of the stomach. Openings: Major openings Opening Level Structures passing - Abdominal aorta Aortic orifice - T12 - Vena azygos - Thoracic duct - Oesophagus Oesophageal https://www.google.com.eg/url?sa=i&url=https%3A%2F%2Fradiopaedia.org%2Fcases%2Fmajor-openings- - T10 - Vagi (gastric nerves) of-the-diaphragm-lateral-view&psig=AOvVaw0z5wSQc9pqI3Spjn3pNXh- &ust=1729566651864000&source=images&cd=vfe&opi=89978449&ved=0CBcQjhxqFwoTCMDTkoLAnokDFQ orifice AAAAAdAAAAABAE - Oesophageal vessels - IVC - Right phrenic nerve Vena caval orifice - T8 - Lymph vessels from the bare area of the liver Medical Points | Diaphragmatic openings The diaphragm has three openings: #Aortic_Hiatus - the most dorsal opening, contains the aorta, azygous vein and... | Instagram Minor openings: 1. Superior epigastric vessels: between the sterna and costal origin. 2. Musculophrenic vessels: through the costal origin. 3. Lower 5 intercostal vessels and nerves: through the costal origin 4. Subcostal nerve and vessels and quadratus lumborum: deep to the lateral arcuate ligament. 5. Sympathetic chain and psoas major muscle: deepto the meial arcuate ligament. 6. Splanchnic nerves: pierce the crura. 7. Inferior hemiazygos vein: pierces the left crus. 8. Left phrenic nerve: pierces the left lobe of central tendon.  Quiz What intercostal nerve supplies the axilla? A) The 1st B) The 2nd C) The 3rd D) The 7th E) The subcostal (the 12th) Answer: B Anatomy of the nose & paranasal sinuses Department of human Anatomy and Embryology Faculty of Medicine Mansoura National University, Egypt Edited by Dr. Fekry Shata  Intended Learning Outcomes (ILOs) By the end of the lecture, the students will be able to: 1- Describe anatomical position of the nose (boundaries, walls & internal structure) 2- Know the nerve, blood supply and lymphatics of the nose 3- Describe the anatomy of nasal sinuses (number, boundaries & termination)  Agenda 1. What are the components of the nose. 2. What are the boundaries of the nose? 3. Mention the blood and nerve supply of the nose 4. Summarize paranasal sinuses (number and connections to the lateral wall of the nose) Anatomy of the Nose  Anatomy of the Nose The nose consists of the external nose and the nasal cavity, both of which are divided by a septum into right and left halves. 25-5  External Nose The external nose has two elliptical orifices called the nostrils, which are separated from each other by the nasal septum. The lateral margin, the ala nasi, is rounded and mobile. 25-6  External Nose The framework of the external nose is made up Above: 1. Nasal bones, the frontal processes of the maxillae 2. Nasal part of the frontal bone. Below: the framework is formed of plates of hyaline cartilage. Rhinoplasty  The Nasal Cavity Nasal Septum Nasal Cavity  Nasal Cavity The nasal cavity extends from the nostrils in front to the posterior nasal apertures or choanae behind, where the nose opens into the nasopharynx. The nasal vestibule is the area of the nasal cavity lying just inside the nostril. The nasal cavity is divided into right and left halves by the nasal septum. The septum is made up of the septal cartilage, the vertical plate of the ethmoid, and the vomer. 25-10 Boundaries of The Nasal Cavity  Walls of the Nasal Cavity Each half of the nasal cavity has a floor, a roof, a lateral wall, and a medial or septal wall. Floor 1. Palatine process of the maxilla 2. Horizontal plate of the palatine bone. Floor  Roof The roof is narrow and is formed Anteriorly: 1. Nasal bone 2. Frontal bones Middle: Cribriform plate of the ethmoid Posteriorly: Body of the sphenoid. Roof  Medial Wall The medial wall is formed by the nasal septum which is formed by the 1. Vertical plate of the ethmoid 2. Vomer 3. Septal cartilage Medial wall Perpendicular Plate of Ethmoid  Lateral wall The lateral wall has three projections of bone called the 1. Superior nasal conchae 2. Middle nasal conchae 3. Inferior nasal conchae. The space below each concha is called a meatus (superior, middle inferior). Sphenoethmoidal Recess is a small area above the superior concha. 25-19 Lateral wall  Nasal Conchae Sphenoethmoidal Recess Middle Meatus Inferior Meatus Superior Meatus Openings in the lateral walls of The Nose  Opening of Sphenoidal Air Frontal Sinus Opening of Air Openings of Frontonasal Sinus Posterior Sphenoethmoi Ethmoidal Air Duct of Frontal dal Sinus Air Sinus Openings of Recess Middle Openings of Anterior Ethmoidal Air Ethmoidal Air Sinus Sinus Openings of Maxillary Air Sinus Bulla Ethmoidal Hiatus is Semilunar Middle Meatus is Inferior Meatus  Sphenoethmoidal recess Receives opening of sphenoidal air sinus  Superior Meatus The superior meatus lies below the superior concha. It receives the openings of the posterior ethmoid sinuses.  Middle Meatus The middle meatus lies below the middle concha. It has a rounded swelling called the bulla ethmoidalis that is formed by the middle ethmoidal air sinuses, which open on its upper border. 25-26  Middle Meatus A curved opening, the hiatus semilunaris, lies just below the bulla. Infundibulum: is the anterior end of the hiatus which is continuous with the frontal sinus. Anterior ethmoidal sinus opens in the infundibulum The maxillary sinus opens into the middle meatus through the hiatus semilunaris.  Inferior Meatus The inferior meatus lies below the inferior concha and receives the opening of the lower end of the nasolacrimal duct, which is guarded by a fold of mucous membrane. 25-28 Blood Vessels of the Nasal Cavities  1. Anterior Ethmoidal 3. The Sphenopalatine Artery Artery From ophthalmic From maxillary 3rd part 2. Posterior Ethmoidal Artery From ophthalmic 4. The Greater Palatine From maxillary 3rd part  Ethmoidal Sphenopalatine arteries artery Ethmoidal Sphenopalatine arteries artery Superior alveolar Greater palatine arteries Greater palatine  Blood Supply of the External Nose 1. Ophthalmic 2. Maxillary 3.Facial artery. 25-32 Bleeding From The Nose (Epistaxis)  The Bleeding Zone Branch from Anterior Ethmoidal Artery Branch from Sphenopalatine Artery Septal Branch of Facial Artery Branch from Greater Palatine Artery Veins of the nose Nerve Supply of the Nasal Cavities A- Special Nerve Supply of The Nasal Cavities Olfactory nerve Olfactory Nerve Rootlets  Olfactory Bulb Cribriform Plate Uncus Nasal Mucosa Olfactory Nerve Rootlets Upper part B- General Nerve Supply of The Nasal Cavities Nerve Supply of the External Nose 1. Ophthalmic nerve (CN V) Infratrochlear external nasal branches of the 2. Maxillary nerve (CN V). infraorbital  Lymph Drainage of the Nasal Cavity The lymph vessels draining the vestibule end in the submandibular nodes. The remainder of the nasal cavity is drained by vessels that pass to the upper deep cervical nodes. 25-43  Posterior Part of The Nose Anterior Part of The Nose Lymph Drainage of The Nose Upper deep Cervical LNs Submandibular Lymph Nodes Paranasal Sinuses  Paranasal Sinuses Paired air spaces In four skull bones 1. Decrease skull bone weight 2. Resonance of voice Named for the bones in which they are housed. 1. Frontal 2. Ethmoidal 3. Sphenoidal 4. Maxillary Communicate with the nasal cavity by ducts. 25-46  Ethmoidal Air Sinuses Supplied by Frontal Air Sinus ant ethmoidal Supplied by Sphenoidal Air Sinus Sphenopalatine Supratrochlear and supraorbital Supplied by nerves nerves pos ethmoidal nerve Nerve supply of paranasal Sinuses  Infraorbital nerve Middle superior Anterior Nerve alveolar nerve superior alveolar nerve supply Maxillary Air Sinus Posterior superior alveolar nerve  Quiz Is the termination of posterior ethmoidal sinus A) Sphenoethmoidal recess B) Superior meatus C) Middle meatus D)Inferior meatus Answer: B  Quiz Bulla ethmoidalis is located in A) Sphenoethmoidal recess B) Superior meatus C) Middle meatus D)Inferior meatus Answer: C  Quiz Is the termination of anterior ethmoidal sinus A) Sphenoethmoidal recess B) Superior meatus C) Middle meatus D)Inferior meatus Answer: C  Thoracic Wall (Muscles & vessels) Department of human Anatomy and Embryology Faculty of Medicine Mansoura National University, Egypt Edited by: Dr. Fikry shata  Intended Learning Outcomes (ILOs) 1. Identify the components of the Thoracic Wall. 2. Name the boundaries and structures passing through the thoracic inlet. 3. Name the boundaries and structures passing through the thoracic outlet. 4. Recognize the origin, insertion, nerve supply, extent, direction of fibers and action of intercostal muscles. 5. Mention the mechanism of respiration. 6. Identify the origin, features and branches of intercostal nerves 7. Recognize the origin, branches and termination of intercostal arteries 8. Recognize the origin, tributaries and termination of intercostal veins  Agenda 1. What are the components of the Thoracic Wall. 2. What are the boundaries and structures passing through the thoracic inlet? 3. What are the boundaries and structures passing through the thoracic outlet? 4. What is the origin, insertion, nerve supply, extent, direction of fibers and action of intercostal muscles? 5. What is the mechanism of respiration? 6. What is the origin, features and branches of intercostal nerves? 7. What is the origin, branches and termination of intercostal arteries? 8. What is the origin, tributaries and termination of intercostal veins?  OVERVIEW OF THORAX The thoracic cavity and its wall have the shape of a cone: narrow above and wide below. the floor of the thoracic cavity (the diaphragm) is pushed upward by the abdominal organs. The thorax includes the primary organs of the respiratory and cardiovascular systems.  Thoracic Wall The Thoracic Wall is composed of: Bones: Forming the thoracic cage Superiorly: Thoracic inlet Inferiorly: Thoracic Outlet Between the ribs: 11 intercostal spaces In the intercostal spaces: Intercostal muscles Intercostal nerves Intercostal arteries Intercostal veins Skeleton of Thoracic Wall (thoracic cage) Vertebral Column Sternum Ribs & Costal Cartilages Thoracic Apertures (openings)  Thoracic Inlet Trachea Oesophagus Thoracic duct Thoracic inlet (superior thoracic aperture) Right Common Boundaries: Carotid artery Left Anteriorly: suprasternal notch. Right subclavian brachiocephalic Posteriorly: 1st thoracic vertebra. artery vein On both sides: inner border of 1st rib and its costal cartilage. Structures passing: pierce the supra-pleural membrane (Sibson’s fascia) 1. Tubes: trachea and oesophagus. 2. Arteries: common carotid, subclavian, internal thoracic and superior intercostal. 3. Veins: right and left brachiocephalic, vertebral and inferior thyroid. 4. Nerves: phrenic, vagus, sympathetic chain and left recurrent laryngeal. Right internal 5. Lymphatic: thoracic duct thoracic artery  Upper border of the body of the first thoracic vertebra Inner border of the right first rib Inner border of the left first Thoracic inlet Left first costal cartilage Right first Manubrium Upper border of costal cartilage Sterni Manubrium Sterni  Thoracic Outlet Boundaries: Anteriorly: xiphoid proces