Note this is at basic level for 2nd year medical students & Allied Health students.

1. Aspire to become good, not great....
Greatness is like a passing cloud,
temporary.
- Sai Baba - Divine Discourse, July 16, 2001.

2. Pathology of
WBC disorders
Dr. Shashidhar Venkatesh Murthy
A/Prof. & Head of Pathology
2013: MB2-HRM-Week 7

3. HRM-Wk7: Fever, bleeding & Back pain
 Mr M.S. 45y, man. Presents to ED: “Very
bad lower back pain, nothing helping it”.
 History:
• Feels unwell? - Very
• Fever? Yes, I think so; intermittent
• Easy bruising -Yes, bruises last few weeks.
 Examination:
• Slim, unwell, pale, Multiple Bruises
• Liver & Spleen enlarged – mild.
• Lymph nodes enlarged neck & axilla.

4. Learning Objectives:
 WBC in health & disease - overview.
 Classification & Common WBC disorders.
 Congenital, Reactive & Cancer.
 Clinical features.
 Pathogenesis
 Laboratory diagnosis
 Blood morphology
• Features (3-4).
• Line diagram.
 Management - brief.
TOP 10 WBC Disorders:
• Leukopenia:
1. Neutropenia
2. Lymphopenia.
3. Pancytopenia
• Leucocytosis:
4. Neutrophilia
5. Eosinophilia
6. Lymphocytosis – IM
7. Lymphadenitis.
• Neoplastic disorders (cancer)
9. Lymphoma
10. Leukemia (AML/ALL,CML/CLL)

5. Teaching Plan & Staff:
 Introduction to WBC disorders:
• Shashidhar Venkatesh Murthy.
 Clinical Cases: GLS 1st hour.
• Ian Irving, Haematologist, TSVH.
 Microscopy Tutorial: GLS 2nd hour.
• Shashidhar Venkatesh Murthy.
 Synthesis Session: Keepad Q&A disc.
• Shashidhar Venkatesh Murthy.
Mon
9am
Tue
1pm
Tue
2pm
Thu
1pm

6. GLS SESSION

7. 8y child with Asthma & multiple scaly skin lesions.
Image shows blood film appearance. ? Cause
1. Viral Infection
2. Allergic reaction
3. Malaria.
4. Bacterial infection.
5. Fungal infection.
1 2 3 4 5
0 0 000
SYNTHESIS SESSION

8. I am here for you….
Email: venkatesh.shashidhar@jcu.edu.au
vmshashi@gmail.com
Need personal guidance? Email me for an appointment.
Office Tel: 4781 4566
Office location – MS136
Emergency?(exam time) Mob: 0416 933 704

9. Small minds discuss people
Average minds discuss events
Great minds discuss solution
Genius silently acts!

10. 10
Normal Blood Cells:
Neutrophil
Basophil
Eosinophil
Lymphocyte
Non granular, Mononuclears
Specific Immunity
Granulocytes, Polymorphs
Non-Specific Immunity

11. Normal WBC Production:

12. Normal Granulopoiesis: CSF
Stimulate
bone marrow
to produce
WBC.
What are the Clinical applications of G-CSF?

13. Lab: CBC - WBC Histogram:
Absolute
Count
% / Differential Count

14. WBC Absolute counts in disease:
Penia PhiliaNeutro
Penia PhiliaEosino
Penia cytosisMono
Penia cytosisLympho

15. Leukopenia: Neutropenia
 Reduction in granulocytes:
• Decreased Production – Marrow.
• Increased destruction – drugs, immune
 When severe – Agranulocytosis.
 Clinical features:
• Infections – chills, fever, fatigue, ulcers.

16. Leukocytosis: Neutrophilia
 Increased granulocytes:
• Acute inflammation, Bacterial infections.
 When severe – Leukemoid reaction.
 Clinical features:
• Infections or Trauma - fever, fatigue.

17. Lymphocytosis: Infectious Mononucleosis
 Increased Lymphocytes:
• Chronic Inflam, Viral, fungal, TB etc.
 Large lymphocytes, more cytoplasm. Irregular,
indented by RBC – also known as virocyte
 Clinical features: Chronic fever, lymphadenopathy.

18. Neutrophilia:
Acute inflammation (Bacterial, trauma, immune, etc)

19. Toxic Granulation & Left shift:
Acute inflammation Bacterial, trauma, immune, etc
Band forms & Phagocytic granules in cytoplasm

20. Leukemoid Reaction:
 Marked increase in
neutrophils. >50,000 x109
 Shift to left  immature
forms.
 Severe infection, trauma,
bone marrow infiltration.
 Looks like leukemia*
(no blasts)

21. Your failure may prove to be
an asset, provided you try to
know why you failed !
--Napoleon Hill

22. Lymphadenitis: Reactive.
 Acute or Chronic.
 Infections, Immune & Cancers.
 Increased large irregular lymphoid follicles
with normal archetecture. (mantle zone).
 Lymphadenitis: Enlarged lymphnodes due
to inflammation or infecitons. Painful.
 Lymphadenopathy – any enlargement, but
commonly used for Cancers – Painless.

23. Reactive lymphadenitis
Dark zone
Light zone
Mantle zone
Macrophage
Tingible body
Macrophage

24. Hemato-oncology: Blood Cancer
 Cancer of blood forming – stem cells (Blasts).
 Leukemia – ‘White’ ‘blood’ – excess WBC.
 Starts in bone marrow or lymphatic tissue.
 Spread to blood & other ‘RES’ tissues only.
(Liver, Spleen & lymphnodes)
 Two Major types: Myeloid & Lymphoid.
 Two clinical presentaiton: Acute / Chronic.
 Many subtypes* – due to several different
mutations – personalized medicine *

25. The goal of mankind is knowledge, which
is inherent in man. No knowledge comes
from outside: it is all inside. What man
'learns' is really what he “discovers” by
taking the cover off his own soul.
- - Swami Vivekananda
„Education‟… from Eduse (latin) to bring out..!
„Doctor‟ … from Dokere‟ (latin) to teach…!

26. Lymphoblast
Leukemia: Cancer of Blast cells.
Acute
Myeloid
Leukemia
Acute Lymphatic Leukemia
Chronic Leukemia
Chronic Leukemia

27. Normal – Acute - Chronic Leuk
Normal
Chronic Myeloid LeukemiaAcute Myeloid Leukemia

28. Hematologic Neoplasms: Classification
 Leukemias: Bone marrow, blood, Blasts
• Duration: Acute/Chronic
• Cell of Origin: Myeloid/Lymphoid
• AML / ALL & CML / CLL
 Lymphomas: – Lymph nodes, tumor
• Hodgkins & Non-Hodgkins.
 Premalignant conditions:
• Myeloproliferative syndromes (MPS)
• Myelodysplastic syndromes (MDS)

29. Leukemia: Clinical Features
 Cancer of Bone marrow – Excess blasts.
 Decreased Haemopoiesis:
• Erythropoiesis – Anemia - RBC
• Leukopoiesis – Infections - WBC
• Thrombopoiesis – Bleeding. PLT
 Bone marrow expansion/destruction:
• Bone pains.
 Extraneous hemopoiesis / spread:
• Splenomegaly
• Hepatomegaly
• Lymphadenopathy. (more in lymphatic malignancy)

30. Leukemia Clinical features:
Bleeding - Petechiae
Lymphadenopathy
Hepatosplenomegaly
Infections - Candidiasis

31. Leukemia Classification
 Acute Leukemias: weeks to months.
• Acute Myeloid Leukemia – AML - Adults
• Many Subtypes: M0, M1 to M7
• Acute Lymphoid Leukemia – ALL - Children
• Many Subtypes: L1, L2 & L3
 Chronic Leukemias: Years.
• Chronic Myeloid Leukemia- CML- Adults
• Chronic Lymphoid Leukemia - CLL –Old age
• Many subtypes:

32. ALL - AML

33. Acute Leukemia: AML/ALL - Blasts
Norm. Lymphocyte
Blast
Blast
Norm. RBC
Norm. Lymphocyte
Norm. RBC
Blast
Normal

34. Self-pity is an opiate!
--Napoleon Hill

35. Lymphoma
 Definition: Tumour of lymphoid tissue
 Etiology: Idiopathic, Genetic, Infective.
 Clinical: Lymphadenopathy, weight loss, Fever.
 Two Major Types: & many subtypes.
 Hodgkins lymphoma (HL) – RS cells.
 Non-Hodgkins lymphoma (NHL) – no RS cells.
• B cell, T cell & Histiocytic lymphoma.

36. Lymphoma Row of enlarged lymph nodes

37. Hodgkins Lymphoma
Big binucleate cancer cells known as
Reed Sternberg Cells (RS cells)

38. Non-Hodgkins Lymphoma:
 Large group of lymphatic neoplasms.
 Clinical: Fever, anemia, infections,
Lymphadenopathy. Spleen+/-.
 No RS cells or eosinophilia
 Complex names and classification.
• Cell type – B, T & Histiocytic “B commonest”
• Clinical – low, intermediate & high grade.
• Histology – Follicular & diffuse.
• Special types: Burkitts lymphoma, Myeloma,
Waldenstroms macroglobulinemia, lennert‟s,

39. Non Hodgkins Lymphoma
Low, Intermediate & High grade.

40. Burkitt‟s lymphoma: large B cell NHL
 Endemic in Africa
 Epstein Barr Virus
(EBV)
 B Cell Lymphoma.
 Dark large B
lymphocytes (malignant)
with plenty of pale
macrophages. (Starry
sky pattern).

41. Multiple Myeloma:
 Malignancy of Plasma cells
(Mature B lymph, Ab)
 Old age, males common.
 Marrow, LN, Blood.
 Multiple, punched out Lytic bone
lesions (Osteolysis)
 Hyper gammaglobulinemia
 Monoclonal antibody peak –
serum protein electrophoresis.
 Immunodeficiency  infections.

42. "Creativity is inventing,
experimenting, growing, taking
risks, breaking rules, making
mistakes, and having fun.
-- Mary Lou Cook

43. Myeloproliferative Disorders.
Myelodysplastic Syndromes.
(Precanceraous stage of blood cancers)

44. Myelo Proliferative Disorders:
 Excess Proliferation, Neoplastic, Old age.
 Organomegaly – Liver & Spleen enlarged.
 Hypercellular BM & Leukocytosis.
 4 types:
• Excess RBC (polycythemia vera)
• Excess WBC (CML)
• Excess Plt (Essential Thrombocythemia)
• Excess Fibroblast (Myelofibrosis).
 Mixed types common, end in leukemia.

45. Polycythemia Rubra Vera (PV)
Hypercellular Marrow,
Red skin & Hepatosplenomegaly

46. ET - Blood Film & clinical.
Plenty of
Platelets
Megakaryocyte

47. Myelo Dysplastic Syndromes:
 Dysplastic Proliferation (abnormal cells)
 Neoplastic, old age, unexplained anemia.
 Abnormal cells destroyed in bone marrow.
 Hypercellular BM & Leukopenia, anemia.
 Commonly known as Refractory Anemia.
 Many subtypes, Mild to severe dysplasia.
 Increasing blasts – poor prognosis.
 Transforms to acute leukemia.

48. Summary:
 Reactive Leukocytosis.
• Neutrophilia, Eosinophilia, Lymphocytosis.
 Reactive Leukopenia.
• Neutropenia, lymphopenia.
 Leukemias – Cancer of Blasts.
• AML/ALL, CML/CLL
 Lymphomas – Tumors of lymphoid tissue
• Hodgkins & Non- Hodgkins (HL, NHL)
 Premalignant conditions
• MPS & MDS:

49. 3 R’s of success:
Respect for self,
Respect for others &
Responsibility for your actions.