phase3 biomed sciences manual 2014 final

8/9/2019 Phase3 Biomed Sciences Manual 2014 FINAL

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Phase 3Biomedical Sciences Manual

2014

Medicine 3802 andArts/Medicine 3841

Version 1.0, January 2014


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Phase 3 Biomedical Scicences Manual 2014Page ii

UNSW Medicine

Phase 3 Biomedical Sciences Manual

2014

PrefaceThis is the 7th edition of the Phase 3 Biomedical Sciences Student Manual produced by the Faculty of Medicineat the University of New South Wales. It contains a large amount of information relevant to the BiologicalSciences component of Phase 3 of the Medicine program. Indeed, the Biological Sciences component of thePhase 3 curriculum is largely covered by the specific learning objectives for each topic elucidated withinthis Manual, as well as by the associated Campus Day activities. The Campus Day program has beenenhanced by a series of seminars on Diagnostic Imaging by experts in the field.

This Manual contains a number of learning resources for students, including trial exam questions for each topicarea, clinicopathological case protocols, and information regarding the assessment of Biomedical Sciences inPhase 3 of the Medicine program at UNSW.

Members of Phase 3 Biomedical Sciences Working Party

A/Prof Gary Velan (Chair), Prof Ken Ashwell, Prof Margaret Morris, Dr Dzung Vu, Dr Trudie Binder (SOMS)Prof Hazel Mitchell (BABS)Prof Ric Day, A/Prof William Sewell (SVH Clinical School)Dr Rachel Thompson (MESO)

Dr Lesley Forster, Dr Sandy McColl, Dr Peter Vine (RCS)

Contributors

Dr Lu Liu (SOMS), Dr Sophia Champion (formerly SOMS), Dr Barbara Booth (formerly SPHCM)A/Prof Bryan Yeo (formerly POWH Clinical School), A/Prof Mike Bennett (POWH Clinical School), A/ProfMarcus Stoodley (formerly POWH Clinical School), Prof David Davies (South Western Sydney Area PathologyService), Prof Stacy Goergen (Monash University, Southern Clinical School)

Original Authors of Clinicopathological Case Protocols

A/Prof Gary VelanProf Nick HawkinsDr Mark DziegielewskiProf Denis Wakefield

© 2014 Faculty of Medicine, The University of New South Wales, Sydney 2052 Australia


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Phase 3 Biomedical Scicences Manual 2014Page iii

Table of contents

Preface ....................................................................................................................................... ii

Guide to Biomedical Sciences in Phase 3 ................................................................................ 1

1. Biomedical Sciences Syllabus ........................................................................................................................1

2. Structure of Phase 3 Biomedical Sciences Teaching ...................................................................................3

3. Phase 3 Biomedical Sciences Correlation Viva ............................................................................................6

Hospital-based staff contacts for biomedical sciences ........................................................... 8

Forensic pathology ................................................................................................................... 9

Department of Forensic Medicine visits ......................................................................................................... 10

2014 Plan for student groups - Department of Forensic Medicine .................................... 12

Code of Conduct ............................................................. ................................................................... ............... 12

Reference section .................................................................................................................... 13

Principles of laboratory investigations - aims, rules and pitfalls ............... .................................................. 13

Interpretation of commonly ordered laboratory tests ............................................ ...................................... 14

Sensitivity, specificity and predictive values - measures of accuracy .......................................................... 15

Key performance metrics for diagnostic tests .......................................................... ...................................... 16

Likelihood ratios ............................................................. ................................................................... ............... 16

Reference intervals for commonly ordered laboratory investigations......................................................... 17

Weight range of normal adult organs ............................................................ ................................................. 23

Acid base balance ............................................................................................ ................................................. 24

Glomerulonephritis .............................................................................. ............................................................ 30

Glomerular disease - summary of features ............................................................................................... ..... 37

Common causes of anaemia............................................................................ ................................................. 41

Groups at risk of acquired immunodeficiency ............ .................................................................. ................ 43

Blood transfusions .......................................................... ................................................................... ............... 44

Monitoring drug concentrations ................................................................................................................ ..... 50

Campus day program ............................................................................................................ 51


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Phase 3 Biomedical Scicences Manual 2014Page iv

Campus day multidisciplinary case-based seminar outlines .............................................. 54

1. Obesity and cardiovascular disease ................................................ ............................................................ 54

2. Infectious diseases ......... ................................................................... ............................................................ 55

3. Post-operative care ......................................................................................................................... .............. 56

4. Head and spinal injury .................................. ................................................................... ........................... 59

Hospital-based tutorial topics ................................................................................................ 64

Specific learning objectives for hospital-based tutorials .................................................... 67

Acute dyspnoea and haemoptysis ................................................................................................................. ..... 68

Anaemia ............................................................................................................. ................................................ 70

Anaphylaxis, allergy and shock ................................................. .................................................................. ..... 71

Back pain and bone tumours ................................................................ ............................................................ 72

Bleeding disorders ................................................................................. ............................................................ 74

Breast lumps ............................................................................... .................................................................. ..... 75

Cerebrovascular disease .......................................................................................................... .......................... 76

Chest pain and vascular disease ..................................... .................................................................. ................ 77

Chronic cough and dyspnoea ....................................................................................................................... ..... 78

CNS tumours and CNS infections ........................................................ ............................................................ 79

Diabetes mellitus - complications ....................... ................................................................... ........................... 81

Dysphagia and haematemesis .......................................................................... ................................................. 82

Endocrine disease .................................................................................................................... .......................... 83

Gallbladder and pancreatic disease ...................................................... ............................................................ 84

Glomerulonephritis and renal failure .......................................................................................................... ..... 85

Gynaecological malignancies ......................................... .................................................................. ................ 86

Haematuria ........................................................... ................................................................... .......................... 87

Hepatitis and chronic liver disease .................................................................. ................................................. 88

Inflammatory bowel disease .............................................................................................................. ................ 89

Leukaemia and myeloproliferative disease .................................................................................................. ..... 90

Lymphoma ................................................................................... .................................................................. .... 91


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Phase 3 Biomedical Scicences Manual 2014Page v

Multisystem disease and polyarthritis ..................................................................................... .......................... 92

Opportunistic infections and AIDS .................................................................. ................................................. 93

Scrotal masses ........................................... ................................................................... ..................................... 94

Clinicopathological case protocols ........................................................................................ 95

Examples of protocol answers ............................................................................................... .......................... 95

Case Protocol 1 ........................................................................................................... ...................................... 97

Case Protocol 2 ........................................................................................................... .................................... 100

Case protocol 3 .................. ................................................................... .......................................................... 102

Case protocol 4 .................. ................................................................... .......................................................... 105

Case protocol 5 .................. ................................................................... .......................................................... 110

Case protocol 6 .................. ................................................................... .......................................................... 113

Case protocol 7 .................. ................................................................... .......................................................... 116

Case protocol 8 .................. ................................................................... .......................................................... 119

Case protocol 9 .................. ................................................................... .......................................................... 123

Case protocol 10 ................ ................................................................... .......................................................... 127

Case protocol 11 ................ ................................................................... .......................................................... 130

Case protocol 12 ................ ................................................................... .......................................................... 133

Case protocol 13 ................ ................................................................... .......................................................... 136

Case protocol 14 ................ ................................................................... .......................................................... 139

Case protocol 15 ................ ................................................................... .......................................................... 142

Case protocol 16 ................ ................................................................... .......................................................... 145

Case protocol 17 ................ ................................................................... .......................................................... 148

Case protocol 18 ................ ................................................................... .......................................................... 150

Case protocol 19 ................ ................................................................... .......................................................... 153

Case protocol 20 ................ ................................................................... .......................................................... 156

Case protocol 21 ................ ................................................................... .......................................................... 159

Case protocol 22 ................ ................................................................... .......................................................... 161

Case Protocol 23 ......................................................................................................... .................................... 164

Case protocol 24 ................ ................................................................... .......................................................... 167


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Case protocol 25 ................ ................................................................... .......................................................... 170

Case protocol 26 ................ ................................................................... .......................................................... 173

Case protocol 27 ................ ................................................................... .......................................................... 176

Case protocol 28 ................ ................................................................... .......................................................... 179

Case protocol 29 ................ ................................................................... .......................................................... 182

Case protocol 30 ................ ................................................................... .......................................................... 184

Case protocol 31 ................ ................................................................... .......................................................... 188

Case protocol 32 ................ ................................................................... .......................................................... 191

Case protocol 33 ................ ................................................................... .......................................................... 194

Case protocol 34 ................ ................................................................... .......................................................... 196

Case protocol 35 ................ ................................................................... .......................................................... 199

Case protocol 36 ................ ................................................................... .......................................................... 202

Case protocol 37 ................ ................................................................... .......................................................... 205

Case protocol 38 ................ ................................................................... .......................................................... 207

Case Protocol 39 ......................................................................................................... .................................... 209

Case protocol 40 ................ ................................................................... .......................................................... 212

Case protocol 41 ................ ................................................................... .......................................................... 214

Case protocol 42 ................ ................................................................... .......................................................... 217

Case protocol 43 ................ ................................................................... .......................................................... 220

Case protocol 44 ................ ................................................................... .......................................................... 223

Case protocol 45 ................ ................................................................... .......................................................... 224

Glossary of terms .................................................................................................................. 225


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Phase 3 Biomedical Scicences Manual 2014Page 1

Guide to Biomedical Sciences in Phase 3

1. Biomedical Sciences Syllabus

The Phase 3 program in Biomedical Sciences builds upon the material learned in Phase 1 and Phase 2. Topics

that were comprehensively covered in earlier Phases are assumed knowledge in Phase 3 and will not be dealtwith in detail again. Please note that the biomedical sciences correlation viva at the end of 5th Year mayinclude references to knowledge from all Phases.

The Phase 3 program stresses understanding of the Biomedical Sciences in the context of clinical scenarios. Thefocus is on clinical presentations, and an approach to diagnosis and management in terms of the underlyinganatomical structures, pathophysiological processes that affect those structures and appropriate pharmacologicaltreatments.

To assist in your development of a sound approach to diagnosis and management based upon knowledge of biomedical sciences, the Phase 3 program includes a series of teaching sessions that cover many of the importanttopics for study. Members of the Phase 3 Biomedical Sciences Working Party have produced this Manual, whichdescribes in detail the aims and objectives of the teaching program. This information provides a useful guide tothe depth of knowledge and understanding that you are expected to achieve. It should also serve to remind youabout material covered in earlier Phases that is included within the scope of knowledge expected by the end of5th Year.

Resource materials for Biomedical Sciences include:• Prescribed textbooks for the Biomedical Science disciplines;• Learning objectives, case protocols and reference materials in this Student Manual;• A series of 20 computer-assisted self-learning modules contained in the Phase 3 Biomedical Sciences

“Survival Pack” CD-ROM;• The “Images of Disease” collection, which is now available online, accessible via a web browser. A

new Images of Disease app is also available for iPhone and iPad – the app can be downloaded via theImages of Disease website http://iod.med.unsw.edu.au (zID and zPass required);

• eDiagnostic - a new online resource for learning about the rational cost-effective use and interpretationof diagnostic investigations, accessible via eMed – (zID and zPass required);

• Online learning modules in Clinical Pharmacology made available via the National Prescribing Service(NPS) website (user name and password available from your Clinical School);

• Online self-assessments for several topics will also be made available via the Biomedical Sciencescomponent of the Phase 3 Moodle module;

• Recordings of Dr Sandy McColl’s Biomedical Sciences tutorials, available via UNSWTV (linked fromthe Phase 3 Moodle module);

• Videos of macroscopic Pathology demonstrations, available via UNSWTV (linked from the Phase 3Moodle module).

Formal teaching in Biomedical Sciences is NOT comprehensive. There are some topics about which you areexpected to inform yourselves that are not covered in the teaching sessions in any detail. Some of these may bedealt with in the Campus Day program. Others that you may wish to review are listed in this Manual.

A major focus of Biomedical Sciences in Phase 3 is to develop your understanding of the rational use ofdiagnostic investigations. To this end, we want you to learn how common investigations are performed, throughyour own study or discussion with your tutors. In addition, you are required to complete a number of educationalactivities that should give you some insight into the provision of diagnostic services. These activities must be

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individually recorded in the Clinical Procedural Skills Acquisition Log Book and each attendance must bevalidated by the signature of the supervising pathologist. They include:

MACROSCOPIC PATHOLOGY DEMONSTRATIONS

A minimum of 4 must be attended during the year. These teaching sessions should include study of tissuesremoved at autopsy and of surgically resected material. For this purpose, students based in metropolitan Sydneywill have the opportunity to visit the Institute of Forensic Medicine in groups, rostered by hospital. No more

than 1 autopsy observed at the Institute may be included towards the required total.

HOSPITAL LABORATORY INVESTIGATIONS

Students must attend at least 4 activities from the list below (or closely related diagnostic procedures).Preferably, they should observe procedures carried out in the course of investigation of patients that they haveclerked. For each such procedure, attendance must be confirmed by the signature of a supervising scientist ordoctor in the Clinical Procedural Skills Acquisition Log Book .

Students Please Note:It is not sufficient to attend the hospital diagnostic laboratories merely to obtain the necessary signatures.Questions related to diagnostic tests will be included in the Phase 3 biomedical sciences correlation viva .We expect you to be able to discuss the correct procedure for specimen collection and delivery, the general

principles of the investigative method, and to interpret the results.

Anatomical Pathology :· processing of tissues for histopathological examination (the "cut-up")· fine needle aspiration biopsy· preparation of a frozen section· examination by immunofluorescence of a renal or skin biopsy and interpretation of results· preparation and examination of tissues by electron microscopy

Haematology: · preparation and examination of a peripheral blood film· ESR, haematocrit, automated cell counts and their interpretation· examination and interpretation of a bone marrow biopsy· use of cytogenetic studies in evaluation of neoplasms· flow cytometry

Clinical Biochemistry: · interpretation of liver function tests, renal function tests· interpretation of laboratory data concerning fluid, electrolyte and acid-base balance· blood gas analysis

Clinical Pharmacology (usually part of Clinical Biochemistry Laboratory)

· clinical data required to interpret a plasma drug concentration result· interpreting a plasma drug concentration result· appropriate dose selection based on drug concentration result

Microbiology: · handling of specimens· interpretation of the results of antimicrobial sensitivity tests· overview of diagnostic procedures in bacteriology and virology· serological methods in diagnosis and epidemiology

Immunology: · performance and interpretation of anti-nuclear antibody testing

· assays for autoantibodies, and their interpretation· flow cytometric analysis of T lymphocytes and subsets· diagnosis of HIV infection/exposure· tests for allergy


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Molecular Genetics: · performance of antenatal screening· chromosomal analysis· screening for genetic predisposition to specific cancers

2. Structure of Phase 3 Biomedical Sciences Teaching

The biomedical sciences teaching program in Phase 3 will commence in STP 2013. The program will run over16 weeks, and will be offered twice per year, in STP/TP1 and TP2/TP3, coinciding with students’ compulsoryYear 5 clinical terms in Medicine and Surgery.

Teaching in the biomedical sciences will consist of 24 hospital-based tutorials over 12 weeks, as well as a total of4 weekly theme-based Campus Days in the remaining 4 weeks.

a) Hospital-Based Tutorials

During Year 5 Medicine and Surgery terms, students are expected to attend 24 x 1.5-hour hospital-based biomedical science tutorials, which will occur twice weekly in the first six weeks of both STP and TP1, and will

be repeated in the first six weeks of TP2 and TP3 at metropolitan hospitals (students based at SutherlandHospital will travel to St. George Hospital for these tutorials). The tutorials will be replicated at the main RuralClinical School campuses, according to their local timetables.

Please note that a proportion of metropolitan-based students will undertake 4-week RUSC attachments at peripheral RCS campuses (Grafton, Kempsey, Lismore, Nowra, Bowral) in the first 4 weeks of their Medicine orSurgery terms. In 2014, it is likely that no Biomedical Sciences tutorials will be offered to students duringtheir RUSC attachments. It is therefore incumbent upon each student to make up the eight tutorials thatthey would otherwise miss by attending tutorials at their “home” hospital, either before (for those studentswith RUSC in TP2 or TP3) or after (for those students with RUSC in STP or TP1) their RUSCattachment. Alternatively (or in addition), students might wish to review recordings of Dr Sandy McColl’sBiomedical Sciences tutorials, available via UNSWTV (linked from the Phase 3 Moodle module ).

The hospital-based tutorials will be led predominantly by conjoint members of academic staff and staffspecialists in the Departments of Anatomical Pathology, Clinical Biochemistry, Microbiology and Haematologyat each of the metropolitan teaching hospitals, as well as by Dr Sandy McColl by videoconference from PortMacquarie to other rural clinical campuses. Video recordings of Dr McColl’s tutorials will be made availableonline to assist revision by all students.

This Manual contains learning objectives and case protocols associated with each tutorial topic, supplemented bya CD-ROM containing 20 self-learning modules. Please note that where there is a self-learning module (ormodules) associated with a tutorial topic, it is expected that you will have explored the relevant module(s)prior to attendance at the tutorial. It is also expected that you should prepare for each tutorial by readingthrough the learning objectives and associated case protocols, as well as consulting biomedical sciencetexts and other resources.

The topics (in approximate order) for hospital-based tutorials are as follows (timetables will vary betweenhospitals):

Chronic cough & dyspnoeaAcute dyspnoea + haemoptysis (associated with CAL modules)Chest pain + vascular disease (modules)Gynaecological malignanciesGlomerulonephritis + renal failure (modules)Haematuria (module)Hepatitis & chronic liver diseaseCerebrovascular diseaseCNS tumours + CNS infections (modules)Opportunistic infections & AIDSBack pain + bone tumours (modules)Multisystem disease + polyarthritis (modules)Endocrine disease (module)


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Complications of diabetesBreast lumpsAnaemia (module)Scrotal massesAllergy and AnaphylaxisBleeding disordersGallbladder & pancreatic disease (module)Dysphagia & haematemesis (module)Leukaemia & myeloproliferative disease (module)Inflammatory bowel diseaseLymphoma (module)

b) Campus Days and Diagnostic Imaging Seminars

Campus Days are scheduled on Tuesdays in weeks 7 and 8 of STP and TP1 (25/2, 4/3, 29/4, 6/5), repeated onTuesdays in weeks 7 and 8 of TP2 and TP3 (24/6, 1/7, 26/8, 2/9). An indicative timetable for the Campus Dayswill be available via the Biomedical Sciences component of the Phase 3 Moodle module. The seminars in TP1and TP2 will be made available for students at RCS via interactive videoconferencing.

The Biomedical Sciences Campus Days will be based on the following themes:

• Obesity and cardiovascular disease• Infectious diseases• Acute surgical emergencies and post-surgical care (including fluid replacement, analgesia and fluid

balance)• Head and spinal injury

The structure of the Campus Days is typically as follows:

Morning (10 am -1 pm): 2 x 90-minute Anatomy workshops based on each theme (these will bereplicated during intensive workshops in Sydney for students based at RCS campuses)

Afternoon (2 pm -5 pm):

i) One-hour Clinical Pharmacology seminar based on each theme (these will be available viainteractive videoconferencing for students at RCS)

ii) Two-hour Integrated Case-Based Multidisciplinary seminar – intended to bring together the biomedical science concepts that facilitate understanding of a clinical presentation relating toeach theme (these will be available via interactive videoconferencing for students at RCS)

As part of the Investigative Medicine stream in the Medicine program, Diagnostic Imaging seminars are nowincorporated into the Phase 3 Biomedical Sciences program. Diagnostic Imaging seminars are scheduled onTuesdays in weeks 3 and 4 of STP and TP1 (28/1, 4/2, 25/3, 1/4), repeated on Tuesdays in weeks 3 and 4 of TP2and TP3 (27/5, 3/6, 29/7, 5/8). An indicative timetable for the Diagnostic Imaging seminars will be available viathe Biomedical Sciences component of the Phase 3 Moodle module. These seminars will be delivered by expertsin the field and will be available via interactive videoconferencing for students at RCS in TP1 and TP2. Theseminars will be based on the following themes:

• Head and spinal imaging• Thoracic imaging• Abdominal imaging• Cancer imaging

c) Online and Experiential Learning

Access will be provided online to Clinical Pharmacology modules via National Prescribing Service (NPS), whichstudents must satisfactorily complete by the end of Phase 3.

Online formative assessments in the Biomedical Sciences with immediate feedback will be made available,linked from Moodle.


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All students will be required to document attendance at 4 hospital laboratories (e.g. Clinical Biochemistry,Clinical Pharmacology, Haematology, Molecular Genetics, Immunology, Microbiology, Anatomical Pathology).

All students will be required to document attendance at 4 macroscopic Pathology demonstrations, of which nomore than 2 can be derived from attendance at autopsies carried out by the Institute of Forensic Medicine(IOFM) at Glebe (for metropolitan-based students), supervised by A/Prof Jo Duflou. A roster for visits to theIOFM by students based at metropolitan hospitals is contained in this Manual.


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Some of the clinical scenarios employed to focus the discussion in the viva may be new to you, while othersmay be modified versions of the case protocols contained in this Manual. Please note that the basicconcepts of Biomedical Sciences disciplines covered in Phase 1 and Phase 2 of the Medicine program willbe assumed knowledge, and will also be assessed in this examination.

The exam will be held on campus at the end of Year 5, currently scheduled for students based at metropolitanhospitals on Wednesday 19th November and Thursday 20th November 2014. The dates and locations of theseexams for students based at RCS are yet to be confirmed.

An example of each type of station is available to you as online formative assessments (complete with criteria fora P grade for each question and notes for examiners following submission of answers) to assist your preparationfor the exam. The formative assessments are linked from the Biomedical Sciences component of the Phase 3Moodle module.

Regarding the grading algorithm for the exam, coarse grading of answers (F, P-, P, P+) for each question at eachstation that a student attends (4) will be converted into numerical marks (F = 30, P- = 50, P = 70, P+ = 90). Themarks will then be averaged to obtain each student’s average mark for each station and overall mark for theexam.

Students in Sydney who achieve an average mark less than 50% for one station only will be given a chance toredeem themselves at a similar station on the morning of Friday 22nd November. Students at RCS campuses inthe same situation will be re-examined on the afternoon of their original vivas.

Further detail regarding the format and timetabling of this examination will be provided during the year.


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Hospital-based staff contacts for biomedical sciences

Prince of Wales Hospital

Hospital Phase 3 Biomedical Sciences CoordinatorA/Prof Elizabeth Salisbury

Department of Anatomical [email protected]: 9382-9025

St. Vincent’s Hospital

Hospital Phase 3 Biomedical Sciences CoordinatorA/Prof Willian Sewell

Centre for Immunology [email protected]: 9295 8434

St. George Hospital

Hospital Phase 3 Biomedical Sciences CoordinatorDr Veli Marjoniemi

Department of Anatomical [email protected]: 9313-3414

Liverpool Hospital

Hospital Phase 3 Biomedical Sciences CoordinatorProf David Davies

Head, South Western Area Pathology [email protected]: 9828-5001

Rural Campus Coordinators

Wagga WaggaDr John Preddy

[email protected]: (02) 6933 5171

AlburyDr Peter Vine


Port MacquarieDr Sandy McColl

[email protected]: ( 02) 6580 7511

Coffs HarbourDr Narelle Mackay



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2014 Plan for student groups - Department of Forensic Medicine• Each group to adopt a “buddy system” and notify facilitator or staff should a student need to leave the

mortuary for any reason.• Facilitator to be present at all times and directing students.• Personal Protective Equipment (supplied) to be utilised by students and facilitator at all times.

Code of Conduct• Students and facilitator are expected to take direction from mortuary staff.• At all times the dignity of the deceased must be respected.• Respect the workspace of the pathologists and mortuary technicians and do not wander. Students must

remain in the designated central aisle at all times unless otherwise directed or invited by staff.• Case summary/narrative is to remain with the designated case and not to be taken away to another area.• Where possible, all students to leave the mortuary area at the same time, keeping noise levels to a

minimum• Strictly NO mobile phones or camera-equipped devices are to be brought into the mortuary area.• Cases deemed sensitive or suspicious are not to be observed by students (as directed) and the

mortuary manager may reserve the right to suspend the mortuary visit in the event there is a high profile case in progress.

• If the above is not adhered to the Mortuary Manager and Duty Pathologist reserve the right to ask the student group to leave the mortuary.


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Reference section

Principles of laboratory investigations - aims, rules and pitfallsDiagnosis of disease is based on careful clinical evaluation of symptoms and signs, syndrome recognition andlaboratory investigation. In many (if not most) diseases the diagnosis is substantiated by direct imaging of organsor tissues or examination of pathological specimens. The pathology laboratory thus plays an important role in

diagnostic medicine.Before embarking on (increasingly!) expensive and often invasive and painful tests it is important to be aware ofthe basic principles that govern the use of such investigations. The three aims of investigations are to:

1. substantiate the provisional diagnosis.2. exclude relevant differential diagnoses.3. evaluate complications and prognosis.

One of the most vexing problems facing new medical graduates is the rational ordering and interpretation oflaboratory tests. Ordering a battery of investigations where one would have sufficed is wasteful and possiblydetrimental to the patient if the redundant tests entail significant risk or discomfort. There are several rules or

priorities that are important to observe in ordering investigations. These are to perform:1. diagnostic rather than non-diagnostic tests.2. painless before painful tests.3. non-invasive before invasive tests.4. inexpensive rather than expensive tests.5. simple rather than complicated tests.6. low risk rather than high risk tests.7. tests that may indicate hazards prior to more invasive tests (e.g. tests of coagulation before liver

biopsy).

Careful consideration should be given to these "aims and rules" before ordering pathology tests. "Screeningtests" should be avoided and the cost of investigations to the patient minimised. Please attempt the case studiesavailable via eMed to compare your use and interpretation of diagnostic investigations to that of experts in the

field.

Remember: Laboratory investigations are no substitute for a carefully obtained history and examination. It isimportant to be aware of the sensitivity and specificity of tests and to be critical of all results that are inconsistentwith the clinical situation or with other laboratory results. All laboratories make mistakes (but rarely)!


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Common causes of artefactual results:

Plasma component Effect Cause

Albumin Increased Prolonged time of tourniquet

Bilirubin Decreased Prolonged exposure to light

Bicarbonate Decreased Prolonged exposure to air

Calcium IncreasedDecreased

Prolonged time of tourniquetCollected into EDTA container

Cortisol Increased Prednisolone therapy; stress

Creatinine Increased Diabetic ketoacidosis

Glucose IncreasedDecreased

Patient not fasting No fluoride preservative

Phosphate Increased Prolonged contact with red cells

Potassium Increased Prolonged contact with red cells;Collected into EDTA container;Haemolysis

Sodium IncreasedDecreased

Contamination by IV infusionHyperlipidaemia;Contamination by IV infusion

Sensitivity, specificity and predictive values - measures of accuracy No diagnostic test is 100% accurate. The predictive value of any test depends upon its sensitivity and specificity.

SENSITIVITY = The number of people with the disorder who test positive, divided by the number of peoplewith the disorder. For example, if a test has a sensitivity of 99% for detecting a certain disorder, only one

person in one hundred with the disorder will return a negative test (i.e. there is a 1% chance of a falselynegative result).

SPECIFICITY = The number of people without the disorder who test negative, divided by the number of people without the disorder. For example, if a test has a specificity of 99% for detecting a certain disorder,only one person in one hundred without the disorder will return a positive test (i.e. there is a 1% chance ofa falsely positive result.

With any laboratory investigation, there is a trade-off between sensitivity and specificity. For example, it may be possible to achieve 95% sensitivity and 90% specificity for a certain test. If 99% sensitivity is desired, it may beachievable but only at the cost of an increased false-positive rate (i.e. the specificity may fall below 90%).

POSITIVE PREDICTIVE VALUE (PPV) = the proportion of those with a positive test result who actuallyhave disease, i.e. the number of true positive tests for a disorder, divided by the number of true positive plusfalse positive tests.

NEGATIVE PREDICTIVE VALUE (NPV) is defined as the proportion of those with a negative test resultwho do not have disease, i.e. the number of true negative tests for a disorder, divided by the number of truenegative plus false negative tests.

Please note that the PPV is proportional to the prevalence of the disorder, while NPV is inversely proportional to prevalence. Therefore a highly sensitive and specific test for a rare disorder will result in a low PPV, but high

NPV.


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Key performance metrics for diagnostic tests

Prof Stacy GoergenClinical ProfesorMonash University

A reminder about the definitions of the key diagnostic test performance metrics – these are derived from the 2 X2 table representing disease state and the results of tests with binary outcomes (i.e. normal / abnormal, positivenegative).

Disease + Disease - Calculations

Positive test result TP FP PPV = TP / (TP +FP)

Negative test result FN TN NPV = TN/ (TN + FN)

Calculations Sens = TP / (TP + FN) Spec = TN / (TN + FP) Accuracy = (TP + TN) /(TP + TN + FP + FN)

Definitions:

• True positive (TP) = number of patients in whom the test result is positive when disease is present• False positive (FP) = number of patients in whom the test result is positive when disease is not present• False negative (FN) = number of patients in whom the test result is negative when disease is present• True negative (TN) = number of patients in whom the test result is negative when disease is not present• Sensitivity = proportion of patients WITH disease who have a positive test result• Specificity = proportion of patients WITHOUT disease who have a negative test result

Likelihood ratios

Note:

• High quality diagnostic tests have LR+ > 10 and LR-


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Reference intervals for commonly ordered laboratory investigations

HAEMATOLOGY

Full Blood CountValues are for whole blood

Haemoglobin (Hb) Adult male 130 - 180 g/LAdult female 115 - 165 g/L

Red Cell Count (RCC) Adult male 4.5-6.5 x 10 12/LAdult female 3.8-5.8 x 10 12 /L

Packed Cell Volume (PCV) Adult male 0.40-0.54Adult female 0.37-0.47

Mean Cell Volume (MCV) 80-100 fL

Mean Cell Haemoglobin (MCH) 27-32 pg

Mean Cell Haemoglobin Concentration

(MCHC)

300-350 g/L

Reticulocyte Count 10-80 x 10 9/L (0.2-2.0%)

Leucocytes (White Cell Count) 4.0-11.0 x 10 9/L

Neutrophils 2.0-7.5 x 10 9/L

Lymphocytes 1.5-4.0 x 10 9/L

Monocytes 0.2-0.8 x 10 9/L

Basophils 50 years 2-14 mm/hrFemale 17-50 years 3-12 mm/hrFemale >50 years 5-20 mm/hr

Tests of HaemostasisValues are for citrated plasma

Activated Partial Thromboplastin Time(APTT)

25-35 seconds

Therapeutic Range for continuous IVheparin

1.5-2.5 x baseline

Prothrombin Time (PT) 13-17 seconds

International Normalised Ratio (INR) 0.9-1.1

Therapeutic Range for oralanticoagulants

2.0-4.5

Fibrinogen 1.5-4.0 g/L

In vivo test

Bleeding time (Simplate II withexperienced operator)


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CHEMICAL PATHOLOGY

Arterial blood gases

pH 7.35-7.45

pO2 75-105 mm Hg)

pCO 2 32-45 mm Hg)

Bicarbonate 24-31 mmol/L

Base Excess -3


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Urate

Urate Male 0.20-0.45 mmol/LFemale 0.15-0.40 mmol/L

Liver Function Tests

Bilirubin Total 2-20 µmol/L

Direct (conjugated)


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Miscellaneous Electrolytes

Copper 13-22 µmol/L

Zinc 12-20 µmol/L

Miscellaneous Enzymes

Prostate Specific AntigenAge 20 - 49: 0 - 2.50 U/LAge 50 - 59: 0 - 3. 00 U/LAge 60 - 69: 0 - 4.00 U/LAge 70 -79: 0 - 5. 50 U/LAge ≥ 80: 0 - 6.50 U/L

Acid Phosphatase Total 5-11 U/LProstatic 0-4 U/L

Alpha-1 antitrypsin 0.9-1.7 g/L

Urinary Electrolytes

Sodium 40-220 mmol/24 hours

Potassium 40-120 mmol/24 hours

Chloride 100-250 mmol/24 hours

Urea 420-720 mmol/24 hours

Creatinine 6-18 mmol/24 hours

Calcium 2.5-7.5 mmol/24 hours

Phosphate 10-40 mmol/24 hours

Urate Male 2.2-6.6 mmol/24 hours

Female 1.6-5.6 mmol/24 hours

Osmolality 50-1200 mmol/kg

Urinary Protein Excretion

Protein


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Immunoglobulins

IgG 6.5-16.0 g/L

IgA 0.6-4.0 g/L

IgM 0.5-3.0 g/L

IgD


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ReferencesRoyal College of Pathologists of Australasia Manual – http://www.rcpamanual.edu.au

See also test databases for hospital laboratories, e.g. Sydpath: http://www.sydpath.stvincents.com.au/spec_db/

http://www.rcpamanual.edu.au/http://www.rcpamanual.edu.au/http://www.rcpamanual.edu.au/http://www.sydpath.stvincents.com.au/spec_db/http://www.sydpath.stvincents.com.au/spec_db/http://www.sydpath.stvincents.com.au/spec_db/http://www.sydpath.stvincents.com.au/spec_db/http://www.rcpamanual.edu.au/


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Weight range of normal adult organs

Organ Weight (grams)

Male Female

Brain 1300-1500 1150-1350

Heart 280-340 200-280

Right Lung 400-650 375-625

Left Lung 350-550 325-525

Liver 1400-1600 1200-1400

Pancreas 70-140 60-120

Spleen 150-200 140-190

Kidney 125-170 115-155

Pituitary Gland 0.5 0.5

Adrenal Gland 5-10 5-10

Ovary 5-7

Testis 10.5-14

Prostate 17.5-22.5

Thymus (M & F) 12-15 (birth) 30-40 (puberty) 10-15 (60 and over)

Thyroid Gland (M & F) 20-30 (coast); 35-50 (hills)


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Acid base balance

A/Prof Daya NaidooFormerly DirectorDepartment of Clinical ChemistryThe Prince of Wales Hospital

PLEASE NOTE: Associate Professor Naidoo’s notes are not intended to be a complete summary of thetopic. This material is intended for use as an adjunct to your private study.

NORMAL EXTRACELLULAR pH = 7.35 –7.45

Metabolism Acid Production

* H+ production: 50 000 mmol/day from fat

30 000 mmol/day from glucose

Elimination by oxidation to water

Hypoxia Lactic Acidosis

Non volatile acidsSulphur & phosphorous containing proteinsPhospholipidsOrganic acids

Eliminated by kidney as titratable acid and NH 4+50 - 100 mmol/day

Volatile acids

* CO 2 production: 22 000 mmol/day

Transport and elimination without acidification


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Alkalosis pH = > 7.45

Increased HCO 3 = Metabolic Alkalosis

Decreased pCO2 = Respiratory Alkalosis

Metabolic AlkalosisIncreased Intake - HCO 3 infusion/ingestionLoss of acid -vomiting, N/G suctionSevere Hypokalaemia

Respiratory Alkalosis Hyperventilation• Psychiatric• Hypoxia• Ventilators

•

Drugs (Salicylates)

Interpretation of Arterial Blood GasesPatient 1 Patient 2 Patient 3 Patient 4 Patient 5

pH 7.10 7.63 7.25 7.40 7.31pCO 2 35 20 60 26 80pO 2 80 90 55 82 65

HCO 3 12 22 18 16 35

Patient 1

Patient 2

Patient 3

Patient 4

Patient 5


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Glomerulonephritis

Prof D.J. Davies

Director of PathologySouth Western Sydney Area Health Service

Glomerular reaction to injury I

1. Introduction

The kidney is affected by a wide variety of diseases. Some are similar to those which occur in other tissues andorgans of the body but others, particularly those affecting glomeruli, are unique. This is probably because of thecomplex architecture of the glomerulus and, from a functional point of view, because it is a capillary bed which,however, functions under pressure which is more usually found within arterioles. Some of the processes whichdamage glomeruli are due to its involvement by systemic diseases which affect capillary beds elsewhere in the

body but others, which are frequently known by the collective name of "glomerulonephritis", have structuraleffects which are confined only to this specialised region of the kidney, although they may possibly be areflection of a systemic disturbance which frequently is believed to be immunological.

Because of the complexities of the subject, which often cause difficulties for medical students, these detailednotes are provided.

Before dealing with the pathology of different glomerular disorders there are a few general principles and problems that require consideration to be followed by a summary of the way in which diseases of the glomerulusdeclare themselves clinically. Then after reviewing the structure of the glomerulus a classification of the

principal glomerular diseases is presented.

2. Problems and principles in kidney pathology

2.1 Nomenclature and classificationUp until the mid-1950's classification of most kidney diseases, particularly glomerulonephritis was

based on the clinical features and there was considerable confusion. With increasing use of renal biopsyfor diagnosis of kidney disease, the whole subject has now been put on a more secure footing with a

pathological classification. As a result, the names now given to glomerular diseases are mainly based ontheir appearance by the light microscope, although in some instances this may be qualified by featuresdetected by the specialised methods of immunohistology and electron microscopy.

However, in contrast to diseases of many other organs, there are considerable limitations to thediagnosis of kidney disease by its examination with the naked eye. While this is adequate forrecognising tumours and inflammation with abscess formation, in the specialised glomerular diseases,

such changes that are evident in the kidney to the naked eye usually only reflect secondaryconsequences of the glomerular disease that have affected the tubules and seldom can anything berecognised which identifies the primary process affecting the glomerulus.

2.2 Correlation of clinical features and pathologyIn many organs different pathological processes can produce the same clinical features. This concept iseasily accepted, for example in the heart, where both ischaemic and valvular heart disease can produce aclinically identical state of congestive cardiac failure. The same situation applies in the glomerulus:different pathological processes can all have the same functional effect, for example causing excessiveloss of protein in the urine or producing kidney failure.

On the other hand the same pathological processes can give rise to different functional effectsdepending on the stage in the evolution in the disease. Early on there may be a selective defect in theglomerulus causing either haematuria, proteinuria or both, but later, as the pathological process


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progresses and disease becomes more widespread, these clinical features will be replaced by the pictureof chronic renal failure.

2.3 Correlation of tissue changes with aetiology and pathogenesisJust because tissue changes look the same under a microscope in two different patients, it does not

necessarily mean that in each the lesions have been caused by exactly the same agent acting in the sameway. In some organs we have no problems with this concept; for example in the lungs

bronchopneumonia can be caused by a number of different infectious agents, all of which cause asimilar type of inflammatory lesion. However, in the glomerulus, some individuals seem to havedifficulty in accepting the fact that a variety of aetiological agents and pathogenetic events can give riseto similar changes in the structure of the glomerulus. Sometimes special methods of tissue examination,such as immunofluorescence, or associated clinical features, or the results of laboratory tests, can give aclue about the cause. However, this is not always the case and it should not be assumed that just becausetwo lesions in different patients look the same under the microscope that they have been caused in thesame way.

3. Effects of glomerular disease

To avoid repetition when talking about individual glomerular disorders, it is useful to have a general idea of thedifferent ways in which glomerular disease can present clinically.

In general, when the disease is mild or early in the course of its evolution, the effects are selective to theglomerular tuft but, as the extent and the severity of the disease increases, more complex systemic effects mayensue. Initially this may only alter the composition of the urine but subsequently there may be a systemic effectof selectively altered glomerular function, e.g. due to loss of plasma protein. Later, as the disease progresses,there may be a more general disturbance affecting the total homeostatic function of the kidney causing eitheracute or chronic renal failure with death in uraemia.

3.1 Urinary abnormalitiesMicroscopic and simple chemical examination of the urine are among the simplest of laboratoryinvestigations and are often done as an adjunct to most medical consultations. In addition, they are astandard part of routine employment and insurance medical examinations and, in quite a number ofinstances, glomerular disease is first detected by urinalysis before the individual has any othersymptoms.

The principal abnormalities are:

3.1.1 Proteinuria

In carrying out its physiological function of preparing an ultrafiltrate of plasma, the glomerular

capillary wall normally retains within the capillaries the plasma proteins, particularly plasmaalbumin, which has a molecular weight of 66,300. The nature of this glomerular permeability

barrier has been the subject of considerable discussion and research and appears to involve avariety of factors, including "pore size" and effects of electrostatic charge. Regardless of theexact site of the permeability barrier, it is now becoming clear that, for this barrier to beeffective, all the structural components of the glomerular capillary wall have to be intact andchanges affecting any of them can lead to leakage of protein into the ultrafiltrate. Tubules havea limited capacity for protein absorption and if glomerular damage is extensive this is soonexceeded and most of the filtered protein appears in the urine. Detection of plasma proteins inthe urine, particularly plasma albumin, therefore is an early and sensitive indicator of diffuseglomerular damage. The detection of protein in urine however is not completely specific as anindicator of glomerular disease. First, inflammation of the lower urinary tract may cause theappearance of a small amount of plasma protein in the urine, although the distinction fromglomerular disease can usually be made clinically and with the aid of other laboratoryinvestigations and the amount present usually is small. Secondly, abnormal low molecular


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3.2.2 The "nephritic" syndromeWith this syndrome patients feel generally ill and frequently there is facial oedema, most oftennoticed early in the morning. Characteristically there is by haematuria (blood in the urine) thequantity is usually small and the macroscopic appearance is sometimes described as “smoky”.Microscopy shows blood and casts in the urine. The blood pressure is increased; this can bemild but sometimes may reach dangerous levels. There is some protein in the urine but the

quantity is less than in the nephrotic syndrome (


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This has a wide variety of causes; some of them may be pre-renal, caused by a disturbance ofrenal blood flow, post-renal caused by acute obstruction of the urinary tract but it can also becaused by diffuse kidney disease. Most often it is due to so-called 'acute tubular necrosis' instates of hypotension and shock but occasionally acute renal failure is caused by fulminatingdisease affecting all glomeruli.

(b) Chronic renal failure - now becoming known as “Chronic kidney disease”This is caused by a slow progressive loss of nephrons over a period of weeks, months or evenyears. The cause is usually some form of renal disease, commonly glomerulonephritis, in anadvanced stage. It may have been preceded by one of the other syndromes referred to above orit may arise without any evidence of previous disease. As with acute renal failure, thefundamental event is loss of power to control the constancy of the internal environment, so thatthere is a rise in plasma creatinine or urea. Frequently there are disturbances of water andelectrolyte metabolism and of acid base balance. When prolonged there may also bedisturbances of calcium and phosphorous metabolism, leading to a variety of secondarymetabolic bone diseases. In contrast to acute kidney injury, urine output is usually increased tothree to four litres per day but its concentration cannot be varied effectively to meet themetabolic needs of the body. The cause of the polyuria has been something of a puzzle but is

now attributed to the few nephrons that survive, operating under conditions of osmoticdiuresis.

4. Structure of the normal glomerulus

While this is a subject with which you should already be familiar, it is worth repeating a few points that arerelevant to the nature and distribution of the various pathological processes about to be described.

The basement membrane is a convenient point of reference, both in the normal and the diseased glomerulus. Itcovers the capillary loops but does not encircle them entirely. It is instead reflected from one loop to the next

over an intercapillary area, the mesangium. As a result there are two types of cell enclosed within the glomerular basement membrane. The first is the endothelial cell that lines the capillary and the second the mesangial cell,which lies in the extracellular mesangial matrix, situated in the intercapillary area.

The endothelial cell has a large nucleus surrounded by a small quantity of cytoplasm and over the rest of thecapillary is spread as a thin layer within which there are multiple small gaps known fenestrae.The mesangial cell has a centrally placed “kidney-shaped” nucleus surrounded by cytoplasm which is relativelyrich in organelles from which stellate processes radiate through the substance of the mesangium.

The outer surface of the glomerular basement membrane is covered by complex specialised cells - the visceralepithelial cells or podocytes. The nucleus is located in the body of the cell situated some distance from theglomerular basement membrane but from the cell body there extends complex branching primary and secondarycytoplasmic processes, terminating as tertiary pedicels or foot processes which cover the entire external surface

of the glomerular basement membrane. The foot processes of adjacent podocytes interdigitate to form a complexintercellular junction and the gap between them is known as the filtration slit, which is thought to be the final part of the route through which the glomerular ultrafiltrate passes. In addition to the resident cells, theglomerulus may also contain some cells from the blood, erythrocytes, neutrophil leukocytes and mononuclearcells. Normally these are few but their numbers are greatly increased in pathological states.

Earlier when talking about proteinuria mention was made of the glomerular permeability barrier, which retainsthe plasma proteins within the capillary lumen. There has been considerable argument about the precise site ofthis. Current knowledge makes much of this argument mis-directed, because it is becoming increasingly evidentthat for the permeability barrier to be effective, the integrity of all components of the glomerular capillary wallmust be maintained. Therefore, compromise of the structure of any of them may lead to the leakage of plasma

protein and, if the defect is large enough, erythrocytes from the lumen of the capillary into Bowman space andthence into the urine. In recent years a number of specific proteins have been identified in the foot process

component of the filtration barrier; their structure is genetically determined and genetic disorders have now beenidentified as causes of glomerular disease in early childhood.


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D i s e a s e

U s u a l c l

i n i c a l

f e a t u r e s

L i g h t m

i c r o s c o p y

I m m u n o h

i s t o l o g y

E l e c t r o n m

i c r o s c o p y

F o c a l a n

d s e g m e n

t a l

g l o m e r u l o n e p

h r i t i s

1 . P

r o t e i n u r

i a a n

d / o r m

i c r o s c o p

i c

h a e m a t u r

i a

2 . R e c u r r e n t m a c r o s c o p

i c h a e m a t u r

i a

( m a y

b e s y n p

h a r y n g

i t i c )

3 . H y p e r

t e n s

i o n , p r o t e i n u r i a

4 . O c c a s

i o n a

l l y n e p h r o

t i c o r n e p h r i t

i c

s y n d r o m e s

F o c a

l a n d s e g m e n

t a l p r o

l i f e r a t

i v e

l e s i o n s ± n e c r o s i s

± c r e s c e n t s

1 . “ I g A

d i s e a s e ” - s

t r o n g

m e s a n g i a l

I g A ± w e a

k e r

I g G

, I g M , C

3 a n

d / o r

f i b r i n

2 . N o

I g A - v a r

i o u s

c o m

b i n a

t i o n s , o

r n e g a t i v e

e x c e p t

f o r f

i b r i n

F o c a

l i n c r e a s e

i n m e s a n g i a l

m a t r i x a n

d c e

l l s ± m e s a n g i a l

d e p o s i

t s ; n e c r o s

i s a n

d f i b r i n ;

c r e s c e n t s a n d

f i b r i n

C r e s c e n

t i c


h r i t i s

R a p

i d l y p r o g r e s s

i v e


h r i t i s , o f

t e n w

i t h

s y s t e m

i c d i s e a s e

1 . C e l

l u l a r c r e s c e n t s i n

> 8 0 % o f

g l o m e r u l i

2 . C e l

l u l a r c r e s c e n t s i n

> 8 0 % o f

g l o m e r u l i s u p e r

i m p o s e

d o n

a s s o c i a t e d g l o m e r u l o n e p

h r i t i s

( e . g . m

e s a n g i o c a p

i l l a r y

G N )

1 . S t r o n g

l i n e a r I g G

± C 3 i n

t u f t a n

d f i b r i n

i n c r e s c e n t

( “ G o o

d p a s

t u r e

s y n d r o m e ”

) ; o r n e g a

t i v e

i n

t u f t a n

d f i b r i n

i n c r e s c e n t

2 . F i b r i n s u p e r i m p o s e

d o n

t y p i c a

l f e a

t u r e s o

f

u n d e r l y

i n g

f o r m o f


h r i t i s

I n f l a m m a t o r y c e

l l s i n t u f t a n

d

c r e s c e n t c e

l l s i n B o w m a n

s p a c e ;

d i s r u p

t i o n o f

b a s e m e n

t

m e m

b r a n e ;

f i b r i n

i n t u f t a n

d

c r e s c e n t ; v a r

i o u s

d e p o s i t s ;

n e c r o s

i s

M i n i m a l c h a n g e

d i s e a s e

1 . P r o t e i n u r i a

2 . N e p

h r o t

i c s y n d r o m e

( u s u a l

l y

s t e r o

i d r e s p o n s i v e )

N i l o r m

i n o r

i n c r e a s e

i n m e s a n g i a l

m a t r i x o r c e l

l s

N i l o r s p a r s e

C 3 ( c h i l d r e n )

o r I g M ( a d u l t )

E x t e n s

i v e s p r e a d

i n g o f

p o d o c y

t e f o o t p r o c e s s e s

F o c a l a n

d s e g m e n

t a l

h y a l

i n o s

i s a n

d s c

l e r o s i s

1 . N e p

h r o t

i c s y n d r o m e

( u s u a l

l y

s t e r o

i d r e s i s

t a n t

)


3 . H y p e r

t e n s

i o n a n

d p r o t e i n u r i a

F o c a

l a n d s e g m e n

t a l h y a

l i n o s

i s a n

d

s c l e r o s i s

( P A S + v e m a s s e s ) - f o c a l

l e s i o n s m a y b e m

i s s e

d o n

b i o p s y

M o d e r a t e

t o s t r o n g

s e g m e n

t a l o r d

i f f u s e

m e s a n g i a l

I g M + C 3 ; o r

n e g a

t i v e ; o r

“ I g A

d i s e a s e ”

( s e e a b o v e )

E x t e n s

i v e s p r e a d

i n g o f

p o d o c y

t e f o o t p r o c e s s e s ;

f o c a

l e p i

t h e l

i a l c e l

l

d i s r u p

t i o n ; s e g m e n

t a l

h y a l

i n o s

i s a n

d s c

l e r o s i s

M e m

b r a n o u s


h r i t i s

1 . N e p

h r o t

i c s y n d r o m e

2 . I s o l a t e d p r o t e i n u r i a a n

d / o r

m i c r o s c o p

i c h a e m a t u r

i a

S u b e p i

t h e l i a l

d e p o s i

t s w

i t h

i n t e r v e n

i n g b a s e m e n

t m e m

b r a n e

“ s p i

k e s ” , p

r o g r e s s i n g

t o c h a i n -

l i k e

a r c a

d e s i n “ l a

t e ” l e s i o n s

S t r o n g

I g G

, u n i

f o r m a n

d

f i n e l y g r a n u l a r c a p i

l l a r y w a

l l

s t a i n i n g ; w e a

k e r C

3 ± I g M

o r I g A ; o c c a s

i o n a

l f i b r i n ;

I g G o c c a s i o n a l

l y

p s e u

d o l i n e a r

S u b e p i

t h e l

i a l d e p o s

i t s

b e t w e e n p r o j e c

t i o n s o f

b a s e m e n

t m e m

b r a n e ;

o v e r

l y i n g s p r e a d

i n g o f

p o d o c y

t e f o o t p r o c e s s e s

T h i n

b a s e m e n

t m e m

b r a n e

“ d i s e a s e

”

R e c u r r e n t m

i c r o s c o p

i c o r

m a c r o s c o p

i c h a e m a t u r

i a

D o u

b t f u l o r m

i n o r

i n c r e a s e

i n

m e s a n g i a l m a t r i x a n

d / o r c e

l l s

N i l o r m

i n o r

I g M ± C 3

A b n o r m a l

l y t h i n g l o m e r u l a r

b a s e m e n

t m e m

b r a n e


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2 . S

e c o n

d a r y g l o m e r u l a r

d i s e a s e

D i s e a s e

U s u a l c l

i n i c a l

f e a t u r e s

L i g h t m

i c r o s c o p y

I m m u n o h

i s t o l o g y

E l e c t r o n m

i c r o s c o p y

D i a b e t i c g l o m e r u l o s c l e r o s

i s


2 . N e p

h r o t

i c s y n d r o m e ;

± h y p e r t e n s

i o n

± r e n a

l f a i

l u r e

+

e v i d e n c e o f

d i a b e t e s

1 . N o d u l a r - m

e s a n g i a l n o

d u l e s o

f

v a r i o u s s i z e s

( K i m m e l s t

i e l -

W i l s o n n o d u l e s

)

2 . D i f f u s e - g e n e r a l

i s e d

t h i c k

m e s a n g i a l m a t r i x

+ s e v e r e a r t e r i o

l o s c

l e r o s i s

N e g a t

i v e o r w e a

k l y p o s i t i v e

a l b u m

i n , i

m m u n o g

l o b u l i n o r

c o m p l e m e n

t i n m e s a n g i u m

±

b a s e m e n

t m e m

b r a n e s

1 . N o d u l a r - l o c a l

t h i c k e n i n g

o f m e s a n g i u m

2 . D i f f u s e - g e n e r a l

l y

t h i c k e n e

d m e s a n g i u m

+ t h i c k b a s e m e n

t m e m

b r a n e

S y s t e m

i c l u p u s

e r y t

h e m a t o s u s

1 . H a e m a t u r

i a , p

r o t e i n u r

i a

2 . N e p

h r o t

i c s y n d r o m e

3 . R e n a l

f a i l u r e

+ v a r i o u s e x

t r a - r e n a

l f e a

t u r e s a n d

a n t i n u c

l e a r a n

t i b o d

i e s

M i m i c s m o s t c o m m o n p r

i m a r y

g l o m e r u l a r l e s i o n s ; o

f t e n

p r o l

i f e r a

t i v e ± n e c r o s

i s ± d e p o s i t s

V a r

i o u s

b u t o f t e n

“ f u l

l

h o u s e ” : I g G , I

g M , I

g A , C 3 ,

C 1 q

V a r

i o u s - o

f t e n p r o l

i f e r a

t i o n ,

n e c r o s

i s a n

d e x

t e n s

i v e

d i s e a s e ; s u

b e p i

t h e l

i a l a n d

/ o r

s u b e n d o t

h e l i a l d e p o s

i t s

L u n g

h a e m o r r h a g e w

i t h

n e p h r i

t i s

( G o o

d p a s

t u r e

’ s s y n d r o m e )

H a e m a t u r

i a ± p r o t e i n u r i a

+ r a p i

d l y

p r o g r e s s

i v e g l o m e r u l o n e p

h r i t i s +

s y s t e m

i c i l l n e s s - l u n g

h a e m o r r h a g e

F o c a

l a n d s e g m e n

t a l o r c r e s c e n

t i c


h r i t i s

L i n e a r

I g G ± C 3 ( a n t

i -

b a s e m e n

t m e m

b r a n e

a n t i b o d y )

P r o l

i f e r a

t i o n

( n o s p e c

i a l

f e a t u r e s

)

H e n o c

h - S c h o n l e i n p u r p u r a

1 . H a e m a t u r

i a

2 . R e n a l

i m p a

i r m e n

t ( r a r e

)

+ s y s t e m

i c i l l n e s s : p u r p u r a , G

I T

b l e e

d i n g

F o c a

l a n d s e g m e n

t a l n e c r o

t i s i n g

o r , r

a r e l y ,

d i f f u s e p r o l

i f e r a

t i v e o r

c r e s c e n t

i c g l o m e r u l o n e p

h r i t i s

M e s a n g i a l

I g A

, f i b r i n

M e s a n g i a l

d e p o s i

t s a n

d

p r o l

i f e r a

t i o n

P o l y a r t e r

i t i s n o

d o s a

( m i c r o s c o p

i c )

1 . H a e m a t u r

i a , p

r o t e i n u r

i a

2 . R a p

i d l y p r o g r e s s

i v e


h r i t i s

+ s y s t e m

i c i l l n e s s a n

d f o c a

l e x t r a -

r e n a

l l e s

i o n s , o

f t e n r e s p

i r a t o r y ;

a n

t i - n e u t r o p h

i l c y

t o p l a s m

i c

a n t i b o d y

( A N C A )

F o c a

l a n d s e g m e n

t a l n e c r o

t i s i n g o r

c r e s c e n t

i c g l o m e r u l o n e p

h r i t i s

U s u a l

l y f i b r i n o n

l y ;

i m m u n o g

l o b u l i n s a n d

c o m p l e m e n

t u s u a l

l y a b s e n t

o r m

i n i m a l

P r o l

i f e r a

t i o n , n e c r o s

i s ;

d e p o s i

t s a b s e n t o r m

i n i m a l

F o c a l g l o m e r u l o n e p

h r i t i s i n

s y s t e m

i c d i s e a s e e . g .

“ F o c a l

e m b o l i c n e p h r i

t i s ”

i n

b a c t e r

i a l e n d o c a r

d i t i s

H a e m a t u r

i a + s y s t e m

i c i l l n e s s a n

d

b a c t e r

i a l e n d o c a r

d i t i s

U s u a l

l y f o c a

l a n d s e g m e n

t a l o r ,

l e s s o f

t e n ,

d i f f u s e p r o l

i f e r a

t i v e


h r i t i s

V a r

i o u s : I g G

± I g M ± I g A ±

C 3 - m e s a n g i a l o r c a p i

l l a r y

w a l

l

P r o l

i f e r a

t i o n ,

d e p o s i t s i n

s o m e c a s e s - m e s a n g i a l

±

s u b e n d o t

h e l i a l


46/238


47/238


Common causes of anaemia

Pathological classification of anaemiaHypochromic Microcytic

Fe deficiencyThalassaemiaAnaemia of Chronic Disease (severe)

Normochromic normocytic

Blood loss or haemolysisMarrow failureAnaemia of Chronic Disease (mild)

Macrocytic

Megaloblastic: Vit B12 or Folic acid deficiencyOthers: Alcohol, Liver Disease, Hypothyroidism

Differential diagnosis of hypochromic anaemia• Defect in haem synthesis

A. Iron deficiency anaemiaB. Anaemia of chronic disease, including chronic inflammation, chronic infection, and malignancy.C. Sideroblastic anaemia

• Defect in globin synthesis A. Thalassaemia syndromes.B. Other haemoglobinopathies.

Causes of folic acid deficiency· Inadequate intake Poor diet, edentulous individuals, alcoholism· Impaired Absorption Disorders of the small intestine, sprue and malabsorption syndromes, intestinal

short circuits, surgical resection, steatorrhoea, infiltrative lesions of the smallintestine, such as malignant lymphoma, Whipple disease etc.

· Drugs Anticonvulsants, oral contraceptives· Increased Requirement Infancy or pregnancy, chronic haemolytic anaemias, myeloproliferative

disorders, lymphoproliferative disorders, neoplastic diseases, skin diseasesincluding psoriasis and exfoliative dermatitis, renal dialysis

· Blocked Activation Folic acid antagonists such as methotrexate, pyrimethamine and pentamidine.

Causes of vitamin B12 deficiency• Inadequate intake Total vegetarianism (vegan)• Impaired absorption Gastric disorders (decreased intrinsic factor), partial or total gastrectomy,

pernicious anemia, alkaline reflux gastritis, gastric carcinoma; Pancreaticinsufficiency; Disorders causing villous atrophy, including sprue, Whippledisease and coeliac disease; Disorders of the terminal ileum, includingregional enteritis, ileal resection, selective malabsorption of vitamin B12;and infiltrative intestinal disease, such as malignant lymphoma.

• Drug administration Para-aminosalicylic acid, neomycin, colchicine, ethanol etc.• Increased requirement Pregnancy, neoplastic disease, hyperthyroidism, hyperactive erythropoiesis,

as in patients with chronic haemolytic disorders.


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• Consumption by intestinal parasites or bacteria Diphyllobothrium latum infestation, Blind-loop syndrome

Causes of iron deficiency• Inadequate intake Vegetarian diet

• Impaired absorption Malabsorption syndromes, gastrectomy, atrophic gastritis• Increased loss Gastrointestinal, e.g. varices, peptic ulcer, aspirin ingestion, carcinoma,

diverticulosis, haemorrhoids, hookworm infestationUterine, e.g. menorrhagia, parturitionRenal, e.g. haematuria, haemoglobinuria

• Increased re

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