1. 1 CALIBRATING THE SYSTEMIC EFFECTS OF INFECTION WITH LABORATORY INVESTIGATIONS Pakistan November 2015

2. 2 Greater accuracy in establishment of: Diagnosis of infection Duration of therapy Safety for implantation of prostheses Assessment and classification for clinical trials Establish prognosis in Medico-legal disputes OBJECTIVES

3. 3   RBC turnover Iron retention in RES   Iron,  ferritin Hypochromia, microcytosis Anisocytosis, anisochromia, basophilia ANAEMIA OF CHRONIC INFECTION Pathogenesis

4. 4 Malabsorbtion of dietary iron  Protein (transferrin-carrier)  Renal haemopoietin  Marrow activity Result – fewer smaller, paler, red blood cells ANAEMIA OF CHRONIC INFECTION Pathogenisis

5. 5 Most often no change Neutrophil leucocytosis Lymphocytosis Thrombocytosis Toxic granulation Shift to left WHITE CELLS IN CHRONIC BONE INFECTION

6. 6  C-reactive protein  Sedimentation rate  Plasma viscosity  Mucoproteins Rouleaux formation  Transferrin (iron carrier) PROTEIN DISTURBANCE IN CHRONIC INFECTION

7. 7 INTERPRETATION OF PROCALCITONIN (PCT) TEST RESULTS S-PCT (ng/ml)INTERPRETATION < 0.5Systemic bacterial infection unlikely 0.5 – 2Local infection possible. Severe sepsis or septic shock unlikely. 2 – 10Systemic (bacterial or fungal) infection likely.  10Severe bacterial infection with systemic inflammation probable (sepsis with organ failure and possible shock). NOTE: PCT HAS A HALF-LIFE OF 24 HOURS PCT DETECTABLE WITHIN 6 HOURS OF ONSET.

8. 8 1191 Patients studied and followed as severity of infection eventually subsided or continued to fluctuate

9. 9 GRADES OF INFECTION ACUTE Grade - 1 Fulminating 2 Subacute 3 Insidious onset 6/3 Acute on chronic 7/3 exacerbation

10. 10 GRADES OF INFECTION CHRONIC Grade - 4 Overwhelming 5 Inflammation 6 Diffuse 7 Localised 8 Not Infected

11. 11 GRADE 4 – OVERWHELMING Large necrotic lesions Copious pus (> 10 ml/day) Systemic toxaemia Impaired immunity Cahexia protein deficit Poor containment (scarring) Procalcitonin elevated X-RayBone destruction > sclerosis and callus formation

12. 12 GRADE 5 – EXTENSIVE + INFLAMMATION Extensive lesion with oedema Cellulitis and adenopathy Possible low-grade pyrexia Lesion moderately contained Moderate purulence (> 5 ml/day) X-RayFlorid periosteal reaction

13. 13 GRADE 6 – EXTENSIVE NOT INFLAMED Extensive lesion (whole bone) No pyrexia Area warm and indurated maybe sinus mild purulence (>2 ml/day) Lesion well contained by scar tissue X-Ray Membranous periosteal reaction

14. 14 GRADE 7 – LOCALISED LESION Local Warmth No induration Pinhole sinus at times Spot of discharge Lesion very well contained X-Ray Sclerotic border - normal bone beyond No clear periosteal reaction: fuzzy surface

15. 15 GRADE 8 - NOT INFECTED Non infective inflammatory disease Haematoma, Aseptic loosening Tumours, Reflex Sympathetic Dystrophy

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23. 23 SERUM FERRITIN : IRON RATIO Grade 453.1 523.8 614.5 7 7.1 8 5.627% Variation

24. 24 Grade1 2 3 4 5 6 7 RBC± - - ± - - HB - - ± - PCV - - ± - MCV ± - - ± - MCH ± - - ± - MCHC - - - ± - - RED BLOOD CORPUSCLES

25. 25 Grade 1 2 3 4 5 6 7 WBC ± ± - - NEUT ± ± - - LYMPH - - ± - - - TOX GRAN - - ± - - L SHIFT - - ± - - PLATELETS - - ± - - LEUCOCYTES

26. 26 Grade 1 2 3 4 5 6 7 ABNORMAL ± - - ± - - ROULEAUX ± - - - SED. RATE ± ± - ABNORMALITIES OF RED CORPUSCLES

27. 27 Grade 1 2 3 4 5 6 7 IRON ± - ± TRANSFERRIN - - - - - SATURATION - - - ± TRANSFERRIN - - - - - FERRITIN ± - IRON STUDIES

28. 28 Haemoglobin Sedimentation Serum Iron Iron Saturation Ferritin Clinical History Signs & Symptoms X-RAY

29. SLIDING SCALE OF SYSTEMIC RESPONSES TO INCREASING INTENSITY OF SEPSIS No Infection Gr. 8 Grade 7 Grade 6 Grade 5 Grade 4  Ferritin:Iron ratio --------------------------------------------------------------------  Ferritin ------------------------------------------------------------------  Serum Iron ---------------------------------------------------  Saturation ---------------------------------------------------  CRP -----------------------------------------------------  ESR -------------------------------------------------  Mean Cell Volume ----------------------------- `  Mean Cell Haemoglobin -------------------------  Hematocrit -------------------------------------  Haemoglobin -------------------------------------- PCT 0.5 to 2 ------ PCT above 2 ---  Leucocytes -----------------------  Platelets ---------------------------  Red Cell Count --------------  Left Shift --------------------- Toxic Granulation ----------- Abnormal Red Cells --------  Transferrin ---  MCHC --------

30. LABORATORY CRITERIA Activity tests Sedimentation Rate Plasma viscosity C-Reactive protein (ESR) Neutrophil leucocytosis Red cell morphology Anaemia Iron deficiency Blood ferritin increased 30

31. CLINICAL CRITERIA Pyrexia Exudate Inflammation Induration Oedema Lymphadenopathy Local warmth 31

32. RADIOLOGICAL CRITERIA Further bone destruction Sequestrum formation Periosteal reaction Fuzzy or layered – (onion) Increasing sclerosis Reconstitution of medulla Re-trabeculation Persistent sclerosis 32

33. EVALUATION OF DEGREE OF INFECTION 33 PointsClinicalLaboratoryRadiological 5Pyrexia Exudate Abnormal reds & whites PCT Transferrin MCHC Lymphocytosis New bone lysis New sequestrum Rough periosteum 4Inflammation Oedema Anaemia Neutrophilia Platelets Smooth periosteal Reaction 3Lymphadenopathy MCV MCH Plasma Viscosity No change or Medulla re-opened 2Local warmth Ferritin Iron CRP Sclerosis 1NothingFerritin:Iron Ratio Less than 7:1 Trabecula normal Negative Isotope

34. 34 POINTS AWARDED POINTSGROUP 3-4Definitely no Infection 1 5-7Probably no Infection 2 8-10Equivocal3 11-13Probable infection4 14-15Definite infection5