Intro to Hematology Flashcards
Compartmentalization of Blood Cells
Stem cells can leave and return to the bone marrow. While circulating in the blood stream, they can potentially be damaged by toxins, medications, etc.
Phagocytes and lymphocytes can enter tissues from the blood stream.
Lymphocytes are the only cells that WBCs that can return to the BM and enter the lymphatic system.
Composition of Blood
- ~50:50 mixture of formed elements and plasma
- Total blood volume ~5L in the average adult
Formed Elements:
- Erythrocytes: anucleate, biconcave disks filled with hemoglobin
- Leukocytes: immune defense
- Thrombocytes: anucleate cell fragments - coagulation
Plasma:
- Water
- Dissolved Ions
- Proteins
Plasma Proteins
Carrier proteins:
- albumin, lipoproteins, transferrin, (+ many others)
Immunoproteins:
- IgG, IgA, IgM, IgD, IgE, complement proteins
Coagulations proteins
Hematopoiesis
Fetal/Neonatal Hematoepoiesis
- primitive hematopoietic cells develop at approximately 4-5 weeks gestation
- Migrate to the liver, bone marrow, thymus and spleen
- **During fetal life, the liver is the primary hematopoietic organ **
Adult Hematopoiesis
- At birth, the primary hematopoietic organ is the bone marrow
- Amount of hematopoietically active bone marrow slowly decreases with age
- 80% in the first decade –> 20% in the 8th decade (but counts are normal. We don’t need a lot of bone marrow to maintain normal counts –> have to have a big hit to change counts)
- Bone marrow susceptibility to toxins increases with age
Composition of Bone Marrow
Stroma
- sinuses lined with endothelial cells and fibroblasts support the development of blood cells
- osteoblasts also play supportive role
- fat cells
Hematopoietic Cells
- stem cells –> mature blood cells
- regulated by highly complex network of >40 cytokines
Both are necessary for blood cell formation - hematopoietic cells must be able to communicate through the stroma
All of the formed elements of the blood develop next to each other
Clumps of one type of cell on bone marrow bx indicative of a tumor.
Normal Hematopoiesis
(types of stem cells)
ALL originate from pluropotent hematopoietic stem cell –> myeloid stem cells or lymphoid stem cells
Requirements for Hematopoiesis
Healthy Bone Marrow
Hormones/Cytokines
- Erythropoietin - hormone from the kidney that sitmulates marrow to produce RBCs (therefore will be anemic from renal failure)
- Thrombopoietin - hormone from liver that stimulates marrow to produce platelets (liver failure = thrombocytopenia)
- Growth Factors - hormone that stimulates marrow to produce WBC
Nutritional Factors
- Iron - RBCs
- Folate
- Vitamin B12
Erythropoiesis
Maturation involves synthesis and accumulation of hemoglobin within the cytoplasm (early cells are purple, become more red with more Hgb)
Nucleus is extruded just prior to release from the marrow
If body is stressed may see nuclear red cells (reticulocytes)
Leukopoiesis
Granulocyte maturation involves condensation and segmentation of nucleus and formation of granules in the cytoplasm
- neutrophils, basophils, eosinophils
Separate process for monocytes (agranular)
Thrombopoiesis
Platelets are derived from megakaryocytes
Megakaryocytes undergo endocytosis in which nucleus divides but cell does not. Cytoplasm begins to fall apart, shedding fragments that are relased from the marrow as platelets
Causes of Bone Marrow Failure
Nutritional deficiency: vitamin B12, folate, iron
Marrow toxins (myelosuppressive): drugs, chemo, radiation, ethanol
Infections: HIV, HBV, HCV, EBV, CMV, parvovirus, B19
Marrow Replacement: infections, sarcoid, leukemia, lymphoma, myeloma, metastatic carcinoma
Autoimmune diseases
Primary bone marrow diseases: Fanconi anemia, paroxysmal nocturnal hemoglobinuria, many others
Evaluation of Blood and Bone Marrow
CBC
- WBC count and differential
- RBC count or Hgb or Hct
- Size and Shape:
- Mean corpuscular volume (MCV) - size of RBCs
- Mean corpuscular Hbg (MCH)
- Platelet (Plt) count and Mean Plt volume (MPV)
Peripheral Blood Smear
Bone marrow - taken from PSIS; expensive and slow
- Aspiration (cell types, numbers)
- Biopsy (cellularity, infiltration)
Red Blood Cells
Size and Shape
- Biconcave disk – maximizes surface area : volume
- Must fit through tiny capillaries, one cell at a time
Function: oxygen and carbon dioxide transport
Contains hemoglobin - tetramer of alpha and beta globin chains; each contains a heme moiety
Clinical Assessment of RBCs
EPO is generated in the kidneys in response to hypoxia, but GFR, urine, or creatinine do not relate to EPO production in any way
Reticulocyte Count - differentiates between destruction and production problem
- i.e. GI bleed = high retic count; if have Fe deficiency will have a low retic count
Normochromic vs. Hypochromic due to Hgb content; related to MCH (average Hgb content of individual RBCs) and MCHC (hgb content in fraction of blood occupied by RBCs)
Size and Shape
- Anisocytosis = variation in size
- Poikilocytosis = variation in shape
- Normocytic = normal size
- Macro/microcytic
- RDW = variation in size (RBC distribution width)
Conditions Associated with Abnormalities of RBCs
Anemias
- low RBC count, Hgb, Hct
- Micro, normo, or macrocytic
Erythrocytosis
- too many RBCs i.e. polycythemia vera
- secondary: hypoxia, abnl EPO production, abnl Hgb, or high oxygen affinity (high altitude or smokers)
Hemoglobinopathies
- i.e. thalassemia or sickle cell disease
Enzymopathies
