Blood Disorders Flashcards
What are the two components of the Hematopoietic System?
- The MYELOID tissue
- The LYMPHOID tissue
What does the myeloid tissue consist of?
bone marrow, red cells, platelets, granulocytes, monocytes
What does the lymphoid tissue consist of?
thymus, lymph nodes, spleen
Where do ALL hematopoietic cells derive from?
hematopoietic stem cells (HSCs)
What are hematopoietic cells capable of?
Self-renewal AND differentiation to all blood cell lineages
Where does Hematopoiesis begin?
in the yolk sack, initial wave of primitive erythroid progenitors
Where are the first Hematopoietic stem cells produced?
aorta-gonad-mesonephros (AGM) region of embryo
What occurs during TRANSIENT PROLIFERATION of the HSCs?
Hematopoietic stem cells leave AGM for placenta and fetal liver
Where do Hematopoietic cells colonize (hint: it is the site of ADULT hematopoiesis)
the bone marrow
What is the proper term for differentiation to all blood cell lineages)
Pluripotency
What is the bone marrow niche?
important for the maintenance of the blood cell system, protection from genotoxic insults
How is the quiescent state of HSCs maintained in the bone marrow niche?
by stromal cells and secreted factors which protect hematopoietic stem cells from genotoxic insults
What is the role of the SPLEEN in relation to blood?
acts as a filter, recycling of old lymphocytes
What is the major repository for platelets and lymphocytes?
the SPLEEN, connects adaptive immune response (white pulp)
What is the role of the thymus?
the site of a T cell differentiation, pluripotent precursors of T cells from bone marrow PROLIFERATE and DIFFERENTIATE
What drains fluid from the tissue?
lymph nodes drain fluid from tissue via LYMPH VESSELS
What are lymph nodes composed of?
Multiple lymphoid lobules, surrounded by lymph-filled sinuses, enclosed by capsule
What is the mechanism of ANEMIA overall?
reduction of total circulating red cell mass below normal limits
How are anemias diagnosed?
ratio of packed red cells to total blood volume (HEMATOCRIT) and hemoglobin concentration
What are the symptoms anemia?
pale skin, weakness, malaise, fatigability
What causes dyspnea when mildly exerted in those with anemia?
lowered oxygen content of the circulating blood
How is anemia classified?
underlying mechanisms, alterations in red cell morphology
How are alterations in red cell morphology assessed?
by completing a peripheral smear
What is looked at in a peripheral smear?
red cell size, degree of hemoglobinization, shape
What are haemoglobinopathies?
inherited disorders of haemoglobin synthesis (thalassaemia) or structure (sickle cell disorder)
What are haemoglobinopathies responsible for?
Significant morbidity and mortality worldwide.
What chromosomal abnormalities are present in majority of white cell neoplasms?
Non-random (translocations)
What plays a crucial role in the survival of normal counterpart of the malignant cell?
mutated or altered genes
What is required for particular diagnosis of neoplastic disorders?
specific mutations as they are associated with Specific tumor types
When are lymphoid tumors widely disseminated?
at time of diagnosis
What is the purpose of mutations in transcriptional regulators?
enhance self-renewal of tumor cells, giving them stem-cell like properties
What do transcriptional regulator mutations collaborate with to drive cell growth?
active tyrosine kinase mutations
What are lymphoid cancers associated with?
immune abnormalities, causing loss of protective immunity and breakdown of autoimmunity
How does Hodgkin lymphoma spread?
In an orderly fashion, where most forms of NHL spread wide early (less predictable)
What is Acute Lymphoblastic Leukemia/Lymphoma?
cancer composed of immature B and T cells, AKA lymphoblasts
What do Lymphoblasts look like?
condensed nuclear chromatin, small nucleoli, agranular cytoplasm
What is the most common mutation in B-cell ALL?
t(12:21) ETV6-RUNX1 translocation
What is RUNX1?
Transcription factor, regulating differentiation of hematopoietic stem cells to mature blood cells
What is the most common mutation in T-cell ALL?
gain of function mutation in NOTCH1, gene essential for T-cell development
What is the greatest success story of oncology?
Pediatric ALL
What percentage of children with ALL obtain a complete remission?
95% of children when treated with aggressive chemotherapy
What is the percentage of adults with ALL that are cured?
35% to 40%
What is Chronic Lymphocytic Leukemia?
example of peripheral B-cell cancer, with cytogenic abnormalities like trisomies and deletions
What are the most common genetic deletions for CLL?
deletion of TP53, deletion of ATM, miR-15a and miR-16-1
What are smudge cells?
disrupted tumor cells, found in a CLL blood smear
Where is the growth of CLL cells confined to?
proliferation centers
What is a Coagulation?
a protective mechanism in response to a vessel injury, seals injury to prevent hemorrhage
What is the process of blood coagulation?
cells and soluble proteins interact to form a intravascular blood clot
What is Blood coagulation also known as?
Hemostasis
What occurs in pathological situations with Blood coagulation?
triggered without vessel injury, formation of a thrombus which obstructs blood flow to embolize a distant organ (thrombosis)
What are the three steps of coagulation?
Primary hemostasis, secondary hemostasis, and clot stabilization/resorption
What occurs in primary hemostasis?
interactions between platelets and injured vessel wall, formation of platelet plug
What occurs in secondary hemostasis?
enzymatic reactions, formation of hemostatic fibrin plug
What occurs during clot stabilization?
restore normal blood flow and integrity of vessel
What are clotting factor disorders?
defects of primary hemostasis, focus on defective platelets > thrombocytopenia
What does thrombocytopenia entail?
small bleeds in skin or mucosal membrane
What is signified by small 1-2 mm hemorrhages in the skin?
Petechiae
What is slightly larger than petechiae but still the same?
purpura
How do clotting factors disorders manifest in secondary hemostasis?
defects of secondary hemostasis which are present bleeds into soft tissue or joints
What is the clinical significance of clotting factor disorders?
depends on blood volume, location, rate of bleeding > iron deficiency anemia
What is Hemophilia A and B?
Both X-linked recessive disorders, more > 1000 mutations leading to range of severity
What is thrombosis?
formation of blood clot inside a blood vessel
What does thrombosis result from?
excessive activation of coagulation or impaired endogenous regulation
What are the three main abnormalities leading to thrombosis?
Endothelial injury, abnormal blood flow, hypercoagulability
What counts as alterations to normal blood flow?
turbulence and endothelial injury
What occurs during turbulence?
turbulence leads to endothelial injury, preventing dilution and inflow of inhibitors
What occurs during endothelial injury?
leads to platelet activation; injury exposes von Williebrand factor
What contributes to endothelial injury?
inflammation, metabolic abnormalities, infection, toxins
What is Hypercoagulability?
Predisposition to thrombosis > can be genetic or acquired
What is prothrombin?
common mutation (2% of population)
Where may thrombi develop in the body?
Anywhere in the Cardiovascular system
Where does arterial (cardiac) thrombi begin in the body?
Begins at the site of endothelial injury or turbulence
Where does venous thrombi usually occur?
Usually in sites of stasis
What is a characteristic of all thrombi?
firmly attached at the point of origin > then grow and become more occlusive
What direction do thrombus grow in?
can grow in either direction > but propagating portion poorly attached
What’s a complication with thrombus?
embolus into distant site > causes tissue dysfunction/infarction
What is embolism?
travels through the blood until they encounter vessels too small
What does embolism cause?
partial/complete vascular occlusion
Where do emboli lodge?
anywhere in vascular tree
What is the most common form of embolism?
Pulmonary Embolism
Where do pulmonary emboli originate from?
deep venous thrombosis (DVT)
What are infarcts?
Areas of ischemic necrosis > commonly caused by arterial occlusion
What is the dominant histologic characteristic of infarction?
ischemic coagulative necrosis > dead tissues preserved for a span of some days
