cancer and bleeding conditions Flashcards
Describe the lineage of tree of blood stem cells
blood stem cell
-> Myeloid stem cells
GIves rise to:
- Myeloblast - granulocytes -(eosinophil, basophil and neutrophil)
- platelets
- red blood cells
- > Lymphoid stem cells
give rise to :
- Lymphoblast- B lymphocyte - plasma cells
- t Lymphocytes
- NK cells
what are the characteristics of acute onset leukaemias
- ONSET?
- Characteritisics?
- CAUSE OF SYMPTOMS and SIGNS
- SYMPTOMS and SIGNS
- ONSET? rapid
- Characteritisics? Immature cells (blasts) in the blood and bone marrow
- CAUSE OF SYMPTOMS and SIGNS: bone marrow failure
- SYMPTOMS and SIGNS:
- Anaemia (↓ Hb): fatigue, pallor, breathlessness
- Neutropenia (↓ neutrophils): recurrent infections
- Thrombocytopenia (↓ platelets): bleeding and easy bruising
Acute myeloid leukaemia
- Cause:
- Risk factors:
- Pathogenesis: where does the problem occur
- Accumulation of what cell?
- Diagnosis, pathology?
- Cause: unknown
- Risk factor: Down’s, irradiation, anti-cancer drugs, age (incidence ↑ with age)
- Pathogenesis: Myeloblast does not differenciate into the granulocyte - NO basophil, eosinophil, neutrophil myeloblast cell
- Diagnosis, pathology? Auer rods on blood film
What is a particularly aggressive sub type of acute myeloid leukaemia?
What gene causes it ?
What condition is it associated with?
Promyelocytic leukaemia
- What gene causes it ? t(15;17)
- What condition is it associated with? Associated with DIC
Acute lymphoblastic leukaemia
- Cause:
- Risk factors:
- Pathogenesis: where does the problem occur
- Accumulation of what cell?
- Diagnosis, pathology?
- Symptoms:
- Cause: unknown
- Risk factor: commonest childhood cancer (75% under 6 years old)
- Pathogenesis: where does the problem occur? Uncontrolled proliferation of lymphoblasts (3/4 of WBC are B cells)
-
Diagnosis, Investigations pathology?
- Bloods: ↑↑ WCC, ↓ Hb, ↓ plts
- BM film: >20% lymphoblasts
-
Symptoms:
- Bone marrow failure symptoms
- organ infiltration (hepatosplenomegaly, enlarged lymph nodes, swollen testes)
What would a mass in the neck of child with ALL indicate,
what symptoms could it cause?
could be T cell ALL -
what symptoms could it cause? thymus enlarged symptoms: mediastinal compression -> stridor, wheeze, SVCO
chronic lymphoblastic leukaemia
Cause:
Risk factors:
Pathogenesis: where does the problem occur
Accumulation of what cell?
Diagnosis, pathology?
Symptoms:
- Cause:
- Risk factors:
- Pathogenesis: where does the problem occur: lymphocytes unable to undergo apoptosis
- Accumulation of what cell?Accumulation of mature incompetent lymphocytes
-
Diagnosis, pathology?
- Bloods: ↑ lymphocytes, ↓ Hb, ↓ neutrophils, ↓ platelets
- Blood film: smear/smudge cells (lymphocytes very fragile)
-
Symptoms
- Asymptomatic in 50%
- Symptoms of BM failure: recurrent infections (including herpes zoster), sx of anaemia, easy bruising/bleeding
- O/E: enlarged non-tender lymphadenopathy, hepatosplenomegaly
What other condition can chronic lymphocytic be associated with?
What is the name of this condition?
- associated with autoimmune thrombocytopenia + anaemia
- Evan’s syndrome
into what more aggressive condition can chronic lymphocytic leukaemia develop into?
• Richter’s syndrome
chronic myloid leukaemia
Cause:
Risk factors:
Pathogenesis: where does the problem occur
Accumulation of what cell?
Diagnosis, pathology?
Symptoms:
- Cause:
Philadelphia chromosome in >80% of those with CML
t(9,22) forming BCR-ABL gene which encodes a constitutively active TK receptor à continuous cell proliferation
- Risk factors:
- Pathogenesis: where does the problem occur: Uncontrolled proliferation of granulocyte precursors in BM but slower progression than AML
- Accumulation of what cell?Ugranulocyte precursors
-
Diagnosis, pathology?
- Bloods: ↑↑ WCC (often >100 x109)
- Cytogenetics: look for Philadelphia chromosome t(9;22)
-
Symptom
- Up to 50% are asymptomatic
- Hypermetabolic symptoms: weight loss, malaise, sweating
- Symptoms of BM failure: lethargy, dyspnea, easy bruising/epistaxis (overcrowding)
- Hyperviscosity symptoms: visual disturbance, headaches, thrombotic event (high RBC)
- Gout
- MASSIVE splenomegaly in 90% (not in acute because not enough time)
What can Chronic myeloid leukaemia develop into?
•Can transform into accelerated phase (10-19% blasts) or into acute leukaemia phase (>20% blasts)
What are the main points to remember for each condition?
AML:
ALL:
CML:
CLL:
AML: Auer rods
ALL: children <6 years
CML: Philadelphia chromosome t(9;22), BCR-ABL gene
CLL: smear/smudge cells
Hodgkin lymphoma
Cause:
Risk factors:
Pathogenesis: where does the problem occur
Accumulation of what cell?
Diagnosis, pathology, Investigation?
Presentation:
- Cause: 50% of cases associated with EBV infection
- Risk factors: Bimodal age distribution peaks in 20-30 and >50y
- Pathogenesis: where does the problem occur? Malignant proliferation of lymphocytes, accumulate in LNs -> lymphadenopathy
- Accumulation of what cell? lymphocytes
-
Diagnosis, pathology, Investigation?
- Lymph node biopsy under microscopy = Reed Sternberg cells
- Ann Arbour staging
-
Presentation:
- Painless enlarging mass (most often in neck, occasionally axilla or groin)
- more painful after alcohol ingestion
- B symptoms: fevers >38, night sweats, weight loss (>10% in last 6 months)
- O/E: non tender firm rubbery lymphadenopathy, splenomegaly +/- hepatomegaly
What cell is this?
reed steinberg cell
non- Hodgkin lymphoma
Cause:
Risk factors:
Pathogenesis: where does the problem occur
Accumulation of what cell?
Diagnosis, pathology, Investigation?
Presentation:
- Cause: Associated with EBV, HIV, SLE, Sjogren’s
- Risk factors: ↑ with age
-
Pathogenesis: where does the problem occur?
- Malignancy of lymphoid cells originating in LNs without Reed Sternberg cells
- 85% are B cell
- 15% are T cell or NK cell
- Diagnosis, pathology, Investigation? Lymph node biopsy –> Ann arbour staging
-
Presentation:
- Painless enlarging mass in neck, axilla or groin
- Systemic symptoms (less common than in HL): weight loss, night sweats, fever
- Organ involvement (more common than in HL): skin rashes, headache hepatosplenomegaly, sore throat, cough
- Signs of BM failure: anaemia, neutropenia, thrombocytopenia
what is an important subtype of Non- Hodgekin Lymphoma?
IN what demographic most prevelant:
Presentation
What would you be able to see under a microscope
- what is an important subtype of Non- Hodgekin Lymphoma? BURKITT’s Lymphoma
- In what demographic most prevelant: •African child
- Presentation: Large LN in the jaw (fast-growing)
- What would you be able to see under a microscope: starry sky appearance
What is this condition?
What does it look like under the microscope?
What is this condition? Burkitt’s Lymphoma
What does it look like under the microscope? starry sky appearance
Multiple myeloma
Cause:
Risk factors:
Pathogenesis: where does the problem occur
Accumulation of what cell?
Diagnosis, pathology?
Symptoms:
- Cause:unknown – possible viral trigger
-
Risk factors:
- ionizing radiation, HIV, agricultural work, occupational chemical exposure e.g. benzene, herbicides
- >70 years. Afrocarribeans > Caucasians > Asians
- Pathogenesis: where does the problem occur? proliferation of plasma cells + production of a monoclonal immunoglobulin (usually IgG or IgA)
-
Diagnosis, pathology?
- Serum/urine electrophoresis: Bence Jones proteins
- Bloods: ↑ ESR, ↑CRP, ↑ urea/Cr, ↑ Ca, ALP normal
- Blood film: rouleax formation
- Serum MONOCLONAL protein >30g/L
- BM aspirate = ↑ plasma cells (>10%)
-
Symptoms:
- ↑ Ca -> tired, thirsty, polyuria, nausea, constipation
- _Renal impairmen_t -> Ig and its fragments (light chains) deposit in the kidney – present in 20% at diagnosis (associated with worse prognosis)
- Anaemia (+ neutropenia, thrombocytopenia) due to marrow infiltration by plasma cells. Also get recurrent bacterial infections due to low levels of other Ig
- Bone pain/lesions: increased osteoclast activation due to myeloma cell signaling ->back/rib pain
What is MGUS?
What could it develop into?
What the symptoms?
What is MGUS? Monoglonal gammopathy of unknown significance
What could it develop into? •1% acquire additional mutations -> Multiple Myeloma
What the symptoms?•Absent CRAB features
What is genetic inheritance pattern of Haemophilia?
X-linked recessive inheritance -> typically affects boys
What are the different types of haemophilia?
Which is more common?
- What are the different types of haemophilia?
Haemophilia A = deficient factor 8 (more common)
Haemophilia B = deficient factor 9
- Which is more common? Haemophilia A = deficient factor 8 (more common)
Girl with what condition can get more easily haemophilia?
Turner syndrome
haemophilia
Cause:
Risk factors:
Pathogenesis: where does the problem occur
Accumulation of what cell?
Diagnosis, pathology, Investigation?
Presentation:
-
Cause :
- Haemophilia A = deficient factor 8 (more common)
- Haemophilia B = deficient factor 9
- Risk factors: FH (but 30% have no FH)
- Diagnosis, pathology, Investigation? prolonged APTT (intrinsic pathway); factor assay confirms diagnosis
-
Presentation:
- Usually presents early in life or after surgery/trauma
- Haemarthrosis after minimal trauma -> swollen painful joints
- Haematomas -> painful bleeding into muscles (increased pressure can lead to compartment syndrome or nerve palsies)
- Excessive bruising or bleeding
- Haematuria
- O/E – as a result of deep bleeding
- Multiple bruises, muscle haematomas
- Joint deformity from haemarthrosis
- Signs of IDA e.g. pallor
- Female carriers are usually asymptomatic but may have low enough levels to cause excess bleeding after trauma
Von Willebrand disease
Cause and types :
Diagnosis, pathology, Investigation?
Presentation:
-
Cause:
- Type 1: reduced levels of normal vWF ( AUTOSOMAL DOMINANT )
- Type 2: defective vWF ( AUTOSOMAL DOMINANT)
- Type 3: complete lack of vWF and highly reduced factor 8 (Autosomal recessive)
- Diagnosis, pathology, Investigation?
- •↑ APTT, ↑ bleeding time, ↓ vWF levels, N plts, normal PT, (↓ factor 8)
-
Presentation: - plts can still attach to subendothelium directly without vWF via GP1a
- More superficial bleeding compared to haemophilias
- Bruising, epistaxis, menorrhagia
- Increased gum bleeding post tooth extraction
- Prolonged bleeding from minor wounds
- HOWEVER type 3 ->bleeding into joints and soft tissues
