Hematology Flashcards
Name the three types of cells that result from lymphopoiesis.
- NK cell
- Plasma (B) cell
- T cell
Name the types of cells that result from the myeloid stem cell:
- Erythrocytes
- Platelets
- Basophils
- Eosinophils
- Neutrophils
- Monocytes/Macrophages
From what does all hematopoietic and lymphopoietic stem cells originate?
The pluripotent stem cells (then myeloid and lymphoid)
Describe the components of blood.
Plasma (55%)
RBCs (45%)
Buffy Coat-WBCs and platelets (<1%)
What is the main function of the RBCs?
Gas transport. Delivery/transport of O2 and getting rid of CO2
Name the two different categories of leukocytes.
Granulocytes and Agranulocytes
Which leukocytes are granulocytes?
Phagocytes: Neutrophils, Eosinophils, Basophils, and Mast cells
Which leukocytes are agranulocytes?
Phagocytes: Monocytes(blood) and macrophages(tissue)
Immunocytes/lymphocytes (T and B): NK cells (granular-atypical)
Describe erythropoiesis.
Pluripotent stem cell is stimulated by erythropoietin which creates a nucleated committed proerythroblast. Next the nucleus shrinks and is reabsorbed creating a normoblast. This then becomes a non-nucleated reticulocyte which leaves the marrow and enters the blood stream. The cell then becomes an eyrthrocyte and Hb synthesis ceases.
What is the normal reticulocyte count and what is it an indication of? Which type of patient would have a higher reticulocyte count?
Less than 1%. It indicates the effectiveness of erythropoiesis. Anemic or sickle cell patients.
What role do the kidneys play in erythropoiesis?
The peritubular cells of the kidney release EPO which stimulates erythrocyte production. Released in hypoxic state.
What is the breakdown of iron in the body at any given time.
- 67% is bound to heme
- 30% stored bound to ferritin or hemosiderin (mononculear phagocytes or hepatic parenchymal cells)
- 3% lost in the urine/sweat/gut/epithelial cells
Explain the iron cycle.
Iron is released by the liver and transported in the plasma as transferrin. The transferrin binds to receptors on the erythroblast membrane (in bone marrow) and transported to the erythroblast mitochondria binding to heme and forming hemoglobin and released into the blood stream. The iron is removed from the bloodstream by macrophages in the spleen and broken down. It is stored as ferrtin in the tissue or transferred as transferrin to bone marrow to begin process again.
Define anemia.
Decrease in the total number of erythrocytes in the circulating blood or in quality/quantity of Hb
Name three common causes of anemia.
1- Decreased erythrocyte production
2- Increased erythrocyte destruction
3- Acute/chronic blood loss
What are MCV, MCH, and MCHC values?
Mean corpuscular volume (cell size)
Mean corpuscular Hb (Hb amount per cell)
Mean corpuscular Hb concentration (Hb amount relative to cell size)
Macrocytic Normochromic anemias include(2):
Megaloblastic Anemia and Pernicious Anemia
Describe Megaloblastic Anemia
A macrocytic normochromic anemia. Unusually large stem cells. Defective DNA synthesis d/t deficiencies in B12 and folate.
Describe Pernicious Anemia
A macrocytic normochromic anemia. Lack of IF from gastric parietal cells=unable to absorb B12 which is necessary for nuclear maturation and DNA synthesis.
What roles do Vit B12 and folate play in Hb synthesis?
Vit B12 aids in DNA synthesis and maturation of RBCs. Folate aids in DNA/RNA synthesis and cell maturation.
Normocytic Normochromic Anemias include(4):
Sickle Cell Anemia
Hemolytic Anemia
Aplastic Anemia
Anemia of Chronic Disease
Describe Sickle Cell Anemia
Normocytic Normochromic Anemia. Genetic defect that causes cells to sickle in the absence of O2. Cells are more stiff, tend to cluster and could thrombose. Tx: bone marrow transplant.
Describe Hemolytic Anemia
Normocytic Normochromic Anemia. Premature/accelerated destruction of RBCs, inappropriate bone marrow compensation, destroy but do not replace fast enough. Could be inherited/acquired, autoimmune, or drug induced. S/s: Jaundice d/t inability to excrete all the bili produced by hemolysis/iron
Describe Aplastic Anemia
Normocytic Normochromic Anemia. Characterized by pancytopenia. Bone marrow failure or suppression of production. D/t excess hypocellular/fatty bone marrow or autoimmune disease that attacks hematopoietic stem cells.
Describe Anemia of Chronic Disease
Normocytic Normochromic Anemia. Mild to moderate anemia (AIDS, RA, lupus, hepatitis, renal failure, malignancies). Decreased erythrocyte life span, ineffective bone marrow response to EPO, altered irone metabolism. Example-renal disease: peritubular cells do not detect hypoxia and do not release EPO.
Microcytic Normochromic Anemias include (3):
Iron Deficiency Anemia
Sideroblastic Anemia
Thalessemia
Describe Iron Deficiency Anemia.
Microcytic Normochromic Anemia R/t chronic blood loss, inadequate intake, or metabolic/functional deficiency. Iron not available for use in the bone marrow
Describe Sideroblastic Anemia
Microcytic Normochromic Anemia Abnormal mitochondrial metabolism=unable to take iron up into mitochondria to make Hb Characterized by Fe overload in the blood and ringed sideroblasts
Describe Thalassemia
Microcytic Normochromic Anemia Imbalance of beta and alpha d/t to mutant gene that suppresses rate of globin chain synthesis causing increased hemolysis resulting in decreased RBC survival rates. Example in beta thalassemia there is an alpha excess d/t a deficit in beta function. May have iron overload requiring chelation.
Myeloproliferative Disorders include (1):
Polycythemia
Describe Polycythemia
Overproduction of RBCs.
Relative: Dehydration, fluid loss results in relative increase in red cell counts and Hb/Hct values
Absolute:
Primary: Abnormality in bone marrow/stem cells leading to overproduction (polycythemia vera= increase in all blood cells, splenomegaly, and increased sensitivity to GF. Goal=prevent leukemia)
Secondary: Increase in EPO in response to chronic hypoxia/tumores. ie-lung cancer, high altitudes.
Name the three components of a blood clot.
Localized vasoconstriction
Platelet activation
Coagulation cascade
Describe the hemostasis sequence.
- Localized vasoconstriction
- Primary Hemostasis: Platelet Activation
- Secondary Hemostasis: Coagulation cascade
- Tertiary Hemostasis- Clot Dissolution
______ are complex cell fragments containing numerous chemical mediators that are released when activated. They display a variety of cell surface proteins that mediate both adhesion to exposed endothelium and aggregation.
Platelets
Describe the intrinsic pathway of the coagulation cascade.
Activated when blood is exposed to surface factors resulting in the activation of Factor XII initiating a cascade that ultimately activated Factor X, the first step in the final common pathway that leads fibrinogen polymerization(by thrombin) to fibrin.
**Workhorse
Activated factor Xa is the site at which the intrinsic and extrinsic coagulation cascades converge. The extrinsic pathway is initiated at the site of injury in response to the release of tissue factor (factor III) and thus, is also known as the tissue factor pathway
Describe the extrinsic pathway of the coagulation cascade.
Activated when blood is exposed to tissue factors during tissue injury. Subsequent activation of Factor VII leads to the final common pathway.
**Spark by activating thrombin
–The mechanism that produces fibrin following tissue injury, beginning with formation of an activated complex between tissue factor and activated factor VII and leading to activation of factor X, which induces the reactions of the common pathway of coagulation
What is required for hepatic synthesis of several coagulation factors?
Vitamin K
Fibrin + activated platelet=_______
CLOT
What does fibrinogen need to be activated to fibrin?
Fibrinogen must be ‘cleaved’ by thrombin.
Homeostasis is a balance of______ and_______
Coagulation and Fibrinolysis
What part does thrombin play in fibrinolysis?
The release of thrombin causes the plasminogen to become its activated form, plasmin which helps to break up fibrin clots by digesting fibrinogen and fibrin. Thrombin also produces antithrombin. Both produce negative feedback for the clotting cascade and help to maintain a balance or homeostasis.
Describe DIC.
An acquired hemorrhagic syndrome in which clotting and bleeding happen simultaneously. Widespread clotting in small vessels leads to consumption of clotting factors and platelets causing bleeding. Ie- incompatible transfusion, abruptio placentae
Von Willebrand factor is released by:
endothelial cells and platelets.
What is leukemia?
Leukemia is a collection of cancers which create a large amount of immature blood cells. These immature blood cells take up space in the bone marrow, preventing the bone marrow from making healthy blood cells such as platelets, red blood cells, and white blood cells
What is the distinguishing factor of Acute Leukemia?
Acute leukemias affect the cells early in the maturation process. They are characterized by the presence of undifferentiated/immature, usually blast cells. The onset is also acute/quick.
What is the distinguishing factor of Chronic Leukemia?
Chronic leukemias affect the cells later in the maturation process. The cells mature but do not function normal. The onset is chronic or slow.
Describe Acute Lymphocytic Leukemia
ALL is characterized by >30% lymphoblasts in BM/blood and is most common in children.
Describe Acute Myelogenous Leukemia
AML is an abnormal proliferation of myeloid precursors; immature blast replacement of normal cells.
Describe Chronic Myelogenous Leukemia
CML is a myeloproliferative disorder. Polycythemia vera is an exemple. Associated with the Philadelphia chromosome.
Describe Chronic Lymphocytic Leukemia
CLL is an accumulation of B lymphocytes in the immature phase, which are unable to activate into plasma cells.
Define Malignant Lymphoma
Cancers that begin malignant transformation of a lymphocytes and proliferation of lymphocytes, histiocytes, their precursors and derivatives in lymphoid tissues. An injury to the DNA of a lymphocyte.
Describe Hodgkin Lymphoma
- Localized to single center group of lymph nodes (cervical, mediastinal)
- Mesenteric nodes rarely involved
- Orderly spread and contiguity
- Extranodal involvement is rare
- Disease is often localized
- Presence of Reed-Sternberg cells (large multinucleated cells, not specific to Hodgkin lymphoma but are necessary for diagnosis)
Describe Non-Hodgkin Lymphoma
- Multiple periphery nodes involved.
- Mesenteric nodes often involved.
- Noncontiguous
- Exranodal involvement is common
- Rarely localized, usually spreads
Fibrinolysis occurs in response to:
Plasmin
How much blood circulates in the body?
5.5L/6 QTS
Albumin
57% of total plasma protein
serves as a carrier molecule for normal components of blood as well as drugs that have low solubility in water
regulation of the passage of water and solutes through the capillaries
globulins
are classified by their movement relative to albumin:
alpha (α) globulins (those moving most closely to albumin)
beta (β) globulin
gamma (γ) globulins (those with the least movement).
Plasma proteins can also be classified into groups by function, which are:
clotting, defense, transport, or regulation
Erythrocytes (red blood cells [RBCs])
responsible for tissue oxygenation
contains hemoglobin, which carries the gases, and electrolytes, which regulate diffusion through a cell’s plasma membrane
What is the lifespan of RBC’s
100-120 days, at which time they are removed by the spleen
Leukocytes (white blood cells [WBCs])
defend the body against microorganisms that cause infection and remove debris, including dead or injured cells of all kinds
neutrophil (polymorphonuclear neutrophil [PMN])
constitute about 57% to 67% of the total leukocyte count in adults
fully mature in the bone marrow
the chief phagocytes of early inflammation
Eosinophils
re capable of amoeboid movement and phagocytosis
eat antigen-antibody complexes and viruses
are induced by mast cell chemotactic factors to attack parasites and other pathogens
Basophils
contain cytoplasmic granules that have an abundant mixture of biochemical mediators, including histamine, chemotactic factors, proteolytic enzymes (e.g., elastase, lysophospholipase), and an anticoagulant (heparin)
Mast cells
reside in vascularized connective tissues just beneath body epithelial surfaces
play a central role in inflammation
their activation and degranulation affect a great number of cells, including those involved in inflammation and healing
agranulocytes
monocytes, macrophages, and lymphocytes
mononuclear phagocyte system (MPS),
specialized endothelial cells in the bone marrow, spleen, and lymph nodes
ingest and destroy (by phagocytosis) unwanted materials, such as foreign protein particles, circulating immune complexes, microorganisms, debris from dead or injured cells, defective or injured erythrocytes, and dead neutrophils
Monocytes
formed and released by the bone marrow into the bloodstream
migrate into a variety of tissues and fully mature into tissue macrophages and myeloid dendritic cells
macrophages
remove old and damaged cells and large molecular substances from the blood
are the major “antigen-processing” and “antigen-presenting” cells that initiate immune responses
initiate wound healing and tissue remodeling
macrophages
remove old and damaged cells and large molecular substances from the blood
are the major “antigen-processing” and “antigen-presenting” cells that initiate immune responses
initiate wound healing and tissue remodeling
Lymphocytes
the primary cells of the immune response
reside in secondary lymphoid tissues as mature T cells, B cells, or plasma cells
Natural killer (NK) cells
kill some types of tumor cells (in vitro) and some virus-infected cells without being induced by previous exposure to these antigens (Natural Born killers!)
Where are NK cells found
develops in the bone marrow and circulates in the blood
found mainly in the peripheral blood and spleen
Platelets (thrombocytes)
formed in the bone marrow
There are approximately 140,000 to 340,000 platelets/mm3 of circulating blood
What is the largest of the secondary lymphoid organs
the spleen
What is so important about the spleen?
site of fetal hematopoiesis
filters blood-borne antigens and cleanses the blood through the action of mononuclear phagocytes
initiates immune responses to blood-borne microorganisms (particularly bacteria)
destroys aged erythrocytes,
serves as a reservoir for blood.
What do the Lymph Nodes do
provide filtration of the lymph during its journey through the lymphatics
are the primary site for the first encounter between antigen and lymphocytes
What is the formation of blood cells called?
hematopoiesis
Where does hematopoiesis happen?
in the liver and spleen of the fetus
only in bone marrow (medullary hematopoiesis) after birth.
Extramedullary hematopoiesis (EH)
blood cell production in tissues other than bone marrow
In adults, EH is
a sign of disease, occurring in pernicious anemia, sickle cell anemia, thalassemia, hemolytic disease of the newborn (erythroblastosis fetalis), hereditary spherocytosis, and certain leukemias.
Bone marrow
primary site of residence of hematopoietic stem cells
What is red marrow and yellow marrow
Adults have two kinds of bone marrow
red marrow (active or hematopoietic marrow; also called myeloid tissue)
yellow marrow (inactive marrow).
Where is red marrow found?
the flat bones of the pelvis (34%) (site of bone marrow biopsies)
vertebrae (28%),
cranium and mandible (13%),
sternum and ribs (10%)
in the extreme proximal portions of the humerus and femur (4% to 8%).
Hematopoietic stem cells (HSCs)
progenitors of all hematologic cells.
Mesenchymal stem cells (MSCs)
maintain HSCs
What are niches
contain stem cells, precursor cells, and terminally differentiated cells
provide a coordinated signaling network necessary to regulate the self-renewal, differentiation and maintenance of HSC
Normal CBC Values
Cute Way to Remember CBC Values
Hematopoiesis in the bone marrow occurs in two separate pools:
stem cell pool is the product of self-renewal that maintains the number of pluripotent stem cells and partially committed progenitor cells
bone marrow pool contains cells that are proliferating and maturing in preparation for release into the circulation, and mature cells that are stored for later release into the peripheral blood
Hematopoiesis involves two stages:
proliferation and maturation.
Hematopoiesis involves two stages:
proliferation and maturation.
What is involved in hemostasis?
a) vasoconstriction
(b) damage to the endothelium and exposure of connective tissue resulting in the formation of a platelet plug
(c) activation of the clotting cascade
(d) formation of a blood clot
(e) activation of fibrinolysis for clot retraction and clot dissolution.
Platelet activation involves three linked processes:
(a) adhesion
(b) activation
(c) aggregation
The pathways of hemostasis include
the intrinsic pathway (also known as the contact pathway) and the extrinsic pathway.
What is the major pathway of normal hemostasis
The intrinsic pathway
What is activated by artificial negative surfaces and also functions in thrombotic state?
the extrinsic pathway
What is the term for breakdown of blood clots?
Fibrinolysis, which is the function of the plasminogen-plasmin system
D-dimer
product of fibrinolysis
LABORATORY FINDINGS FOR VARIOUS ANEMIAS
Macrocytic versus Microcytic
hyper versus hypochromic
