Cells of the blood Flashcards
What is TPO ?
- Thrombopoietin - hormone produced by liver.
Stimulates production of megakaryotes from bone marrow to eventually form platelets.
Thrombocytopenia - can give TPO analogues to encourage production of platelets
What is the JAK2 pathway what is it responsible for ?
Jana associated kinase.
(cant be assed to learn mechanism )
Mutations in JAK2 gene involved in myeloproliferative diseases. - over proliferation of cells of the myeloid lineage ( RBC , WBC and platelets )
What happens to Hemopoietic stem cells as you age.
In bone - Volume of hemopoietic stem cells (red bone marrow ) decreases with age.
It is replaced by fat (yellow bone marrow)
Red bone marrow - production of RBC ,EBC , Platelets
Yellow bone marrow - fat storage.
Axial skeleton - ribs , skull , etc - this is where most of the Haemopoeitic stem cells are
Appendicular skeleton ( long bones - eg. femur, tibila , fibrula etc) - yellow bone marrow.
What is Lymphoma ?
Proliferation of the Lymphoid tissue. (Solid tumor )Cancer of the Lymphatic system
Originates in B and T lymphocytes
2 types -
0 Non - Hodgkin’s Lymphoma
- either b cell ( most common) or T cell (less common)
0 Hodgkin’s Lymphoma
- can be found anywhere there is lymphoid tissue - peripheral lymph nodes, e.g neck , chest etc
- In organs - spleen
What is the pathway for creation of B CELL from Bone marrow?
Naïve B cell activated (by T helper cell ) ——— > Centroblast (each centroblast will have different surface IGM antibodies due to point mutations in variable region (somatic hypermutation - increase/ decreases affinity to antigen — if decreases undergo apoptosis , if increase develop further) ——- > Centrocytes ——->differentiate into Memory B cell or Plasmoblast.
(during this conversion of centrocyte to plasmoblast it undergoes class switching)
Plasmoblast —- > plasma cell—- > antibodies.
Risk factors of Non - Hodgkin’s lymphoma ?
0 Immunological - HIV, Autoimmune conditions
0 Viral - HIV , Epstein Barr virus
0 genetic - SKID , Klinefelter , HCV (Hepatitis C )
0 Environmental - pesticides , herbicides , smoking.
0 H. Pylori infection
- Anything that weakens immune response
- medicines ( Secondary immunodeficiency )
- viruses
etc.
0 Age - can occur at any age - but most diagnosed over 75
What are the types of Non - Hodgkin’s Lymphoma ?
0 Indolent/ low grade NHL - Slow growing and responsive to therapy , but not typically curable with standard approaches
-follicular lymphoma - Abnormal b cell develop in clumps - follicles
* Lymphadenopathy - a lump or
several lumps around the body
(lymphoma cells building up in
lymph nodes)
* Can get Follicular
Lymphoma n Bone marrow
causing :
- anaemia
-Thrombocytopenia
- Neutropenia
- some tymples of aplastic large cell lymphoma - breast implant associated , primary cutaneous.
0 Aggressive/ high grade: Rapidly progressive but responsive to chemotherapy and often curable
- Diffuse large B cell lymphoma (
DLBCL) - most common high grade
* Abnormal B cells , larger than normal
but healthy cells , b cells spread
out under microscope not grouped
together.
* usually notice swollen lymph
node on neck , groin and
armpit - but can happen
anywhere.
- Burkitt's lymphoma - very rapidly
growing - different types
* sporadic - occurs occasionally
and irregularly - most common
- can be sometimes linked to
Epstein's Barr virus.
* Immunodefiency associated -
linked to HIV and post - organ
transplant
* Endemic - occurs in
populations where malaria is
common . usually develops in
Young children
- Mantle cell Lymphoma - B cells , originates from the mantle zone ( outer zone surrounding the central germinal centre.
- aplastic Large cell Lymphoma - T cell lymphoma
* ALK - positive ALCL - Genetic mutation cause cells to produce Anaplastic lymphoma kinase) - test for this kinase.
* ALK - negative - no kinase produced. - Peripheral Lymphocytosis
- bone marrow involvement
Asymptomatic peripheral lymphadenopathy (non tender)
Symptoms ?
The most common symptom of non-Hodgkin’s lymphoma is
0 lymphadenopathy,
0 sometimes accompanied by other symptoms
- fever,
- weight loss,
- night sweats.
(B symptoms / inflammatory symptoms - triad associated with lymphoma ) - indicates more advanced systemic disease rather than local.
- pruritus, (ITCHING)
What some of the extra symptoms that can be seen with NH lymphoma ?
Extra
In some patients, enlarged mediastinal and retroperitoneal nodes produce pressure symptoms. The most important of these are
0 Compression of the superior vena cava (SVC): Shortness of breath and facial edema (SVC syndrome)
0 Compression of the external biliary tree: Jaundice
0 Compression of the ureters: Hydronephrosis (swelling of the ureters)
0 Bowel obstruction: Vomiting and obstipation
0 Interference with lymph drainage: Chylous pleural or peritoneal fluid or lymphedema of a lower extremity
When you refer for suspected NH Lymphoma ?
Adults
0 Consider suspected cancer pathway referral (appointment within 2 weeks) -unexplained lymphadenopathy or splenomegaly- take into account associated symptoms
Children / young people
0 Consider a very urgent referral (appointment within 48 hours) for specialist assessment for non-Hodgkin’s lymphoma -
unexplained lymphadenopathy or splenomegaly - take into account associated symptoms
Associated symptoms - ( B symptoms triad) - weight loss, fever , night sweats also pruritus.
Treatment of Non- Hogkins Lymphoma ?
Diagnostic procedure (order)
- excision biopsy - removal of tumour and skin around it )
- Needle core biopsy- extraction of a sample of tissue ( bigger sample than fine needle aspiration) - if risk of surgery outweighs benefits excisional biopsy
- ( Diagnosis - not confirmed after Core needle - try excisional if possible instead of a second core needle ).
Staging
Offer FDG-PET-CT(fluorodeoxyglucose-positron emission tomography-CT) imaging to confirm staging for people diagnosed with:
- stage I diffuse large B-cell lymphoma by clinical and CT criteria
- stage I or localised stage II follicular lymphoma if disease is thought to be encompassable within a radiotherapy field
- stage I or II Burkitt lymphoma with other low-risk features.
Causes of Lymphocytosis ?
- Viral infection
- Haem maligancy
- Smoking
- Infectious Mononucleosis ( Infectious disease caused by EBV - epstein’s barr , Cytomegalovirus (CMV) most commonly - other virus can cause it. )
- these virus stay in the body for the rest of your life .
Reactive lymphocytosis - presence of reactive lymphocytes ( varied forms - large cleaved nucleus. deeply blue nucleus , enfold cytoplasm around red cells .
What are the causes Neutrophila ?
Most common - infection
- inflammation (chronic)
- drugs - steroids,
- pregnancy
- smoking
- leukaemia , lymphoma (haem malignancy / myeproliferative disease )
- necrosis
- Asplenism -
* can be functional or anatomical
anatomical - been removed in surgical procedure (elective or emergency splenectomy )
Functional - lack of function.Causes neutrophilia - take out spleen nowhere for the neutrophils to chill so increase in blood.
What is Asplenism ?
Asplenism -
* can be functional or anatomical
0 anatomical - been removed in
surgical procedure (elective or
emergency splenectomy )
0 Functional - lack of function.
Causes neutrophilia - take out
spleen nowhere for the neutrophils to
chill so increase in blood.
Management of Splenectomy ?
High risk of infection - especially below Age 16 and above over 50.
A history of previous invasive
pneumococcal disease
Splenectomy for underlying haematological malignancy, particularly those who have received splenic irradiation or who have ongoing GvHD are also at continuing high risk. Patients with active ongoing graft- versus-host disease
0 Antibiotic Prophylaxis -
1ST - line for adults and children
Penicillin (phenoxymethylpenicillin) -
type of penicillin .
* Amoxicillin - given instead if
H.influenzae cover needed for
children
Pencillin allergy - Give Erythromycin (adult)
- Clarithromycin (children )
Minimum - 2 years after surgery - but prefably life long - adults
Up to age of 16 , and 2 years after surgery , life long preffered .
discontinuation possible - 5 years and over with sickle cell disease who have received pneumococcal immunisation + no history of severe pneumococcal infection
0 Therapetic - if they get infection :
- Amoxicillin or clarithromycin 500mg
0 Children should be caught up with vaccination schedule.
