1. ‘A ‘complex’ case’ Dr Draper & Dr Thomas General Medicine Firm 3rd Yr Medical Students: A. Caleyachetty, Z. Rahman, & N. Shah 18/11/03

2. History - 59 yr old Caucasian female Non specific feeling of unwellness Ambulance called At A&E, Colles fracture was discovered and c/o chest pain. Chest Pain - Left Sharp pain, Not associated with breathing, Intermittent Developed cough whilst in hospital

3. Cough Severe cough especially at night White and yellow sputum No sweats or fever No haemoptysis Appetite good No recent weight loss

4. Past medical history Arthritis in both knees and ankles Painful in mornings Stairs difficult. “Depression, anxiety and Agoraphobia” – Chronic Schizophrenia (20 years) Asthma during childhood which prevented participation in sports No recollection of Primary TB infection THREADS

5. Medication History Olanzapine Fluoxetine

6. Family History Only child Father died aged 59 years – Acute MI, diabetic Mother suffered from “depression” Died at 82 years of Colon Ca.

7. Social History Solitary existence in sheltered accommodation. Current Smoker 15/day 40 years. Drinks 2 cans of strong lager a day (20 units/week) “Self Medication for the depression”

8. Systems Enquiry CVS & Resp System as above GI/GU/CNS –NAD

9. On Examination Middle aged caucasian woman Temp – pyrexia/low grade Cachexic

10. On examination CVS Haemodynamically stable HS I + II + O JVP ----> Respiratory Normal BS bilaterally No crackles/wheeze

11. On examination Abdominal Examination Normal No organmegaly Musculoskeletal Exam Normal, except plastered left wrist

12. Blood Tests Normal WCC Normal Hb  D dimmer Normal CRP Normal U+Es Normal LFTS Normal Calcium

13. Radiology Abnormal CXR Patchy/nod shadowing RUC Loss of Vol Fibrosis and cavitations (?)Calcified

14. CXR

15. Microscopy Sputum Sample ZN Stain +ve for Acid Fast Bacilli Culture Pending

16. Treatment Plan Isolation 2 weeks 6/12 Regime 2/12 quadrruple therapy Isoniazid Pyrazinamide Ethamabutmol Rifampicin 4/12 double therapy if fully sensitive Vit. D replacement if Vit. D levels are low Checks LFTS & Visual Acuity

17. Mycobacterium Tuberculosis Mycobacterium are aerobic, non-sporing rod shaped bacilli Size 2-4  m long Classified as Acid-Alcohol fast bacillus (AAFB) Appears as red rods when stained by Ziehl-Nielsen stain

18. Mycobacterium Tuberculosis - Pathogenicity The cell wall is key to its pathogenicity. Escapes killing by macrophages Induces cell mediated immunity

19. Epidemiology WHO estimates that…. 1.72 billion have latent infection 15-20 million people have active infection 3 million deaths are attributable to TB In the UK, 7,000 cases were reported (2000) 2,938 new cases of TB in London (2000) which was nearly half the total number of cases for England & Wales

20. Resurgence of TB Inadequate programme for disease control Multiple drug resistance Comorbidity with HIV

21. Predisposing Factors Immunocompromised individuals e.g. AIDS patients Drugs that cause immunosuppression e.g corticosteroids Health workers in contact with TB patients Chronic Renal failure Malnutrition Malignancy 25-hydroxycholecaliferol deficiency

22. Stages of Pathogenesis Exposure PRIMARY TB SECONDARY TB (ReactivationTB)

23. Primary TB Develops in previously unexposed i.e sensitive persons Source of bacilli exogenous Features Induces hypersensitivity Primary Focus formed which may contain viable bacilli Majority of cases, healing occurs - fibrocalcific nodule in the lung, no clinical squelae Uncommon - development of progress Primary TB/Dissemination of TB in Lung/Bloodstream

24. Pathogenesis TB spread by infectious airborne droplet nuclei Infections droplet nuclei are inhaled & localise in the distal airways. TB bacilli are ingested by alveolar macrophages, stimulating local inflamm. reaction Macrophages spread bacilli to hilar lymph nodes CD4 T cells IFN-y Vit.D Activate macrophages

25. Pathogenesis Primary/Ghon Complex Focal pulmonary lesion w/regional lymphadenopathy Usually asymptomatic Lesion ~10mm diameter Central zone of caseous necrosis Surrounded by palisaded epithelioid histocytes, lymphocytes Tubercle Granuloma

26. Secondary TB Pattern of disease that occurs after development of specific immunity Occurs Features Progression of Primary TB Reactivation of Primary TB infection Exogenous Reinfection Typically located in the apex of one or both upper lobes Extensive Caseous necrosis seen Tissue destruction manifested as cavity formation in lungs Caseous granulomas seen