B4 Flashcards
Define the leukocytosis
Increase in the number of leukocytes in the peripheral blood
Define the leukopoenia
Decrease in number of leukocytes
Explain about the hematopoietic neoplasms
- A single cell in the marrow or peripheral lymphoid tissue undergoes genetic alteration.
- Genetic alteration causes the increased activation of oncogenes or decreased activity of tumour suppressor genes.
A)Genetic mutation accumulate
B) Malignant transformation of pluripotential stem cells
C) Clonal expansion of stem cells
D) Blocks in differentiation of abnormal cells
E) Accumulation of blasts in acute leukaemia
Define leukaemia
- Group of disorder characterised by the accumulation of malignant white cells in bone marrow.
- Neoplastic proliferation of WBC precursors
- Characterised by > 20% blasts in the blood and bone marrow
State the classification of Acute Myeloid / Myeloblastic Leukaemia (AML)
M0- Undifferentiated AML M1 - AML without maturation M2 - AML with maturation M3 - Acute promyelocytic leukaemia M4 - Acute myelomonocytic leukaemia M5 - Acute Monoblastic leukaemia M6 - Erythroleukaemia M7 - Acute megakaryoblastic leukaemia
Classify Acute Lymphoblastic Leukaemia ( ALL ) based on FAB ( morphology of blasts )
L1- Small homogenous blasts
L2 -Heterogenous blasts
L3 - Large homogenous blasts
Describe the clinical features of AML & ALL
AML
Age : Young adult
Features
Anemia , Infection , Bleeding ( AML M3 ) , Gum Hypertrophy ( AML M4 , M5)
ALL Age : Children or old age Features : Anemia , Infection ( fever + low WBC ) , Bleeding ( Low platelets )
: Generalised lymphadenopathy , Meningeal infiltration
Explain the lab diagnosis of AML & ALL (include peripheral smear )
- Hb low ( 4 -5gm% )
- Normocytic , normochromic anemia
- Total leukocyte count - increase ( 10-30000/mm3 )
- Normal granulocytes are reduced
- Platelet count - decreased
Peripheral smear :
AML :
Myeloblast ++ ( > 20%)
Maturation according to subtype ( M0 - M7 ) * contain Auer rod
Acute lymphoblastic leukaemia (ALL)
Lymphoblast ++ (20%)
Granulocyte decreased
Morphology according to subtypes (L1,L2, L3)
Explain the cytochemical stain of AML & ALL
AML. ALL
Myeloperoxidase +ve -ve
Sudan. +ve. -ve
PAS. -ve. +ve
Nonspecific- +ve in M5 —
enterase
Explain the cell changes in ALL based on FAB classification
L1 - Homogenous small blasts , scanty cytoplasm , regular round nuclei , inconspicous nucleoli
L2 - Heterogenous blasts , variable cytoplasm , irregular nucleus , large nucleoli
L3 - Large homogenous blasts , basophillic cytoplasm , round nucleus , prominent nucleoli , cytoplasmic vacuolation , Burkitt’s lymphoma
Explain the prognosis of Acute Myeloid Leukaemia & ALL
AML : poor , with treatment modalities in the young it is improving
ALL : overall , >85%of children can now expect to be cured .
: The cure rate in adults is 5% over the age of 70years
Describe the pathophysiology of Chronic Myeloid Leukaemia (CML)
- due to gene mutation in a pluripotent stem cell & clonal proliferation
- characterised by presence of Philadelphia chromosome due to t(9:22 ) forming a BCR-ABL fusion gene
- produces a mutant tyrosine kinase protein which mimic the effects of activation of growth factor receptor , hence causing uncontrollable proliferation of granulocytic , megakaryocytic and erythroid precursors.
- leads to leukaemia ( accumulation of WBC in bone marrow and blood)
Describe the clinical features of CML
Massive splenomegaly : slow progressive , discomfort , pain or ingestion due to spleen
Hypermetabolic state : Weight loss , lassitude , anorexia
Anaemia : Pallor , dyspnoea & tachycardia
Bleeding tendencies : Bruising , epistaxis , menorrhagia or other sites because of abnormal platelet function
Gout or renal impairment caused by Hyperuricemia from excessive purine breakdown
Explain the blood findings and peripheral smear of CML
Blood findings
- Normal / decreased of haemoglobin
- Increased in total leukocyte count
- Increased Platelet
Peripheral smear
RBC - Normocytic / Normochromic anemia
WBC - Leukocytosis
Increase in all stages of myeloid precursor
I) Myelocytes , Metamyelocytes , bands are predominant
II) Blasts < than 10%
III) increase eosinophilia
IV) Increase Basophilia
2) BM changes
- cellularity increased ( increase in myeloid precursors )
- blasts <10%
- eosinophilia , basophilia , megakaryocytosis
3) Staining
- staining do not get stained by neutrophil alkaline phosphatase in CML
4) Cytogenetic analysis , PCR
- Presence of Philadelphia chromosome ( ABL-BCR fusion gene )
5) Biochemical test
- elevated uric acid due to increased purine breakdown
Describe the prognosis of CML
Clinical course of CML depends on stages of disease
1) Chronic phase
2) Accelerated phase
3) Blast crisis
Blast crisis:
- Increasing anemia
- Thrombocytopenia
- Increased Basophilia
- Increased blasts (>20%)
- Myelobalstic / Lymphoblastic crisis
- New chromosome abnormalities
Define the thrombocytopenia
- platelet count below the lower limit of normal ( < 150,00 / microL ) for adults
Classify 4 possible process leading to thrombocytopenia
I) Failure of marrow production
- bone marrow failure of haematological disease ( example : aplastic anemia , leukaemia ) usually causes pancytopenia . However, thrombocytopenia may be the only sign of intrinsic marrow disease or marrow suppression associated with infection or chemotherapy
2) Shortened lifespan
- Platelets can be destroyed in the circulation
- Most common mechanism in clinical syndromes such as immune thrombocytopenia.
3) Sequestration : Splenomegaly can cause low platelet counts because of pooling in the enlarged organ
4) Dilution. Normal platelets are diluted by massive blood transfusion
Explain the Pathogenesis of Idiopathic thrombocytopenia (ITP)
- Antiplatelet antibodies ( mostly IgG directed against surface glycoproteins ( ex: GPIIb/IIIa , Gl Ib/IX ) bind to surface protein in platelets. »_space;> in autoimmune thrombocytopenic purpura , platelets are mainly destroyed in the reticuloendothelial system , especially the spleen»_space;> premature removal of platelets from the circulation by macrophages of the reticuloendothelial system resulting In thrombocytopenia.
- Normal lifespan of platelet is 10 days but in ITP is few hours
Explain the Difference of Acute ITP & Chronic ITP
Acute ITP
- Childhood
- Frequently previous viral infection
- Platelet count often <20
- Occur few weeks long
- Around 90% spontaneous remission
Chronic ITP
- Adult life
- Unusual previous viral infection
- Variable platelet count
- Insidious onset
- Years / lifelong duration
- Rare spontaneous remission
Explain the clinical feature of Idiopathic thrombocytopenia purpura ( ITP )
Any kind of mucocutaneous bleeding A) Epitaxis B) Menorrhagia C) Gum bleeding D) Petechiae E) Purpura F) Echymoses
Explain the laboratory diagnosis of ITP
- diagnosis of exclusion
- decreased platelet count ( < 100,000/microL)
- Increased bleeding time
- normal PT and APTT
- Presence of autoantibodies in serum
- Normal erythrocytes and leukocytes
- Increases megakaryocytes on bone marrow biopsy
- platelets reduced in number and increased in size
Define Thrombotic Thrombocytopenia purpura ( TTP) and its Pathogenesis
- due to deficiency of protease enzyme ADAMTS
- ADAMTS 13 is responsible to rate production of normal functional vWF.
- It does this by cleaving ultra high weight multimer of vWF as it is released from endothelial cells.
- In the absence of enzyme activity , these u,tra large multimer bind platelets and occlude the microcirculation
- Decrease platelet count
Describe primary haemostasis
1) Platelet adhesion
- platelets adhere to injured endothelium via binding GPIb to vWF in sub endothelial matrix
2) Platelet activation
- Platelets changes from rounded disc to flat plates with spiky protrusion which greatly increase the SA
- Platelet also release secretory granules containing TXA2 and ADP
3) Platelet aggregation
- released TXA2 & ADP induce platelet aggregation through platelet GPIIb-IIIa receptor binding to fibrinogen
- primary haemostatic plug is formed
Describe secondary hemostasis
- Coagulation cascade which leads to conversion of soluble fibrinogen into insoluble fibrin to strengthen the platelet plug & facilitate clot formation.
( Refer the picture )
Intrinsic
( extrinsic : 7 )
12 —>11 —> 9 —> 8 —> 10 —> 5 —> 2 —> 1
State the classification of bleeding disorder w/ examples
1) Vascular defects
- scurvy : lack of Vit C impair collagen synthesis —> fragile BV —> bleeding
- Cushing syndrome : hypercortisolemia —> abnormal collagen —> bruising
2) Platelet defects :
I)Thrombocytopenia : BM suppression , megaloblastic anemia , hypersplenism , dengue fever , thrombotic microangiopathies , SLE
II)Bernard- Soulier disease : mutation in GPIb / IX/V complex , leads to giant sized platelets
III) Glanzmann thrombasthenia : mutation in GPIIb-IIIa complex
IV) Afibrinogenemia
V) Von-Willebrand disease
VI) Aspirin use : lowers TXA2 levels —> impair platelet aggregation
3) Defects in coagulation cascade
I) Hemophilia A : lack of factor VIII
II) Hemophilia B / Christmas disease : lack of factor IX
III) Hemophilia C: factor XI deficiency
IV) Vit K deficiency : inactivated factor II, VII , IX , X
Describe the differences between platelet / vessel wall disease and coagulation disease
Platelet/ vessel wall disease
- Mucocutaneous bleeding is more common
- Petechiae , purpura and ecchymoses are seen
- Sex patients are equal
Coagulation disease
- Deep bleeding ( organs , muscle , joints ) is more common
- Rarely seeen Petechiae , purpura & ecchymoses
- Sex of patients >80% male ( X-linked disease )
Describe the Pathogenesis of disseminated intravascular coagulation
Too much clotting —> occlusion of microvasculature + too little clotting —> prolonged bleeding
1) DIC is triggered widespread endothelial damage & collagen exposure or entry of procoagulant material into the circulation
( ex: septicemic , obstetric procedure , major trauma , carcinomas)
2) Leads to release of tissue factor which causes widespread micro vascular thrombosis
3) Microvascular thrombosis leads to tissue ischemia , necrosis and organ failure
4) At the same time , platelet and clotting factor are consumed , leading to prolonged bleeding
5) Fibrinolysis ends to release of fibrin degradation products which inhibit hemostasis
List the causes of DIC
1) Obstetric complications
- Abruptio placentae
- Retained dead fetus
- Septic abortion
- Amniotic fluid embolism
- Toxemia
2) Infections
- Sepsis , Malaria , Aspergillosis
3) Neoplasms
- Carcinomas of pancreas , prostate , lung and stomach
4) Massive tissue injury
- Trauma , Burns , Extensive surgery
5) Miscellaneous
- Acute intravascular Hemolysis , snakebite , giant hemangioma
Describe the lab diagnosis of DIC
1) Thrombocytopenia <150k cells / uL
2) Low fibrinogen concentration
3) Prolonged prothrombin , APTT and thrombin time
4) high levels of fibrin degradation products eg D- dimers in serum and urine
5) Presence of haemolytic anemia & RBC fragmentation
- due to damage caused when passing through fibrin strands in vessels
Define Lymphadenitis
- Enlargement in one or more lymph nodes , usually due to infection
- Reactive lymphadenitis is nonspecific response which may be acute or chronic
Explain the example and changes seen in acute lymphadenitis
- Due to microbial infections
- Example :
A) Cervical ( infection of oral cavity )
B) Axillary ( Infection of arm )
C) Inguinal ( Infection of lower extremities )
Changes seen A) Nodes enlarge B) Nodes become tender C) Nodes are soft or matted together D) Area / Skin around node become red E) Nodes may fill with pus ( an abscess )
