Hematopoiesis and Peripheral Blood Flashcards
What is hematopoiesis?
the process by which blood cells are formed
What comes from hematopoietic stem cells?
red blood cells
granulocytes
monocytes
platelets
lymphocytes
What comes from myeloid precursors?
RBCs
platelets
monocytes
neutrophils
eosinophils
What comes from lymphoid precursors?
NK cells
B cells
T cells
Hematopoiesis locations by age
3-8wks gestation
6-30wks gestation
9-28wks gestation
28wks-onward
Yolk sac
Liver
Spleen
Bone Marrow
Hematopoiesis occurs in bone marrow throughout the skeleton until puberty when it moves where?
vertebra and pelvis, skull, sternum (axillary locations)
What are the components of the bone marrow?
hematopoietc cell compartment with vasculature and stem cells
marrow stromal compartment with fenestrated endothelia, adipocytes for energy and macrophages
hematopoietic growth factors produced by stromal compartment
How is hematopoiesis regulated?
by hematopoietic growth factors
What is the role of Stem Cell Factor (SCF)
produced by fetal tissue and bone marrow
weake stimulator of hematopoiesis
makes stem cells responsive to cytokines
What is the role of IL3?
influences the replication and growth potential of hematopoietic progenitors (myeloid lineage)
What is the role of IL6?
Stimulates megakaryotcutes and neutrophil production
key factor in leukemoid reaction
What is the role of IL2?
What is the effect of IL2 and IL6 together on the lymphoid lineage?
T cell growth factor (lymphoid lineage)
B cell growth factor
What is the role of GM-CSF?
stimulates the formation of all leukocytes and reticulocytes
comparable to G-CSF for increasing neutrophils during neutropenia, but G-CSF is used more often clinically
What is the role of G-CSF?
stimulates and increase in neutrophils
treatment for neutropenia after chemotherapy or bone marrow transplant
produced bny endothelial cells, fibroblasts, and macrophages
What is the role of M-CSF?
Stimulates an increase in monocytes and macrophages
What is the role of erythropoietin (EPO)
Produced in kidney
simulates formation of RBCs
EPO stimulators are used in treatment for anemia
What is the role of TPO?
TPO is produced in the liver
stimulates an increase in megakaryocytes and platelets
TPO receptor agonists are used therapeutically
What are reticulocytes?
What happens to the reticulocyte count in hemolytic anemias where RBCs are destroyed?
enlarged, immature erythrocytes which show a residual netowork of ribosomal material (RER)
What is the evolution of the leukocyte?
myeloblast: basophilic cytoplasm, no granules
promyelocyte: large granules in cytoplasm, nucleoli maybe present
myelocyte: oval nucleus, azurophilic granules, 2’ granules
metamyelocyte: indented nucleus is major feature
What is the evolution of lymphocytes?
B and T lymphoblasts: no cytoplasmic granules
B and T cells: T cells mature in thymus, B cells in bone marrow
Plasma cells (from B cells): eccentrically plcaed nucleus with perinuclear hoff generated from activated B cells in spleen and LN with help of T cells and then travel back to bone marrow
What is the evolution of platelets?
megakaryoblasts: with large oval/kidney nucleus and basophilic cytoplasm
Megakaryocyte: large multilobed nucleus with endomitosis and invaginations of plasma membrane
Platelets: break off from megakaryocyte
What are the three compartments for monocytes/macrohages to live in?
Takes 24 hours to transport among the compartments
stem cell to monoblast in bone marrow
monocyte in blood
macrophage in tissues
(specialized in various tissues)
What is MCV?
What is MCH?
What is MCHC?
What is RPI?
average volume (or size) of RBC
average mass of Hb in RBC
concentration of Hb in a given volume
What is anisocytosis?
What is poikilocytosis?
variation in size and increase in RDW
variation in shape (beta thalassemia)
What does it mean if something is an “absolute neutropenia” as apposed to neutropenia?
refers to the actual number of cells, not a percentage
What are the causes of iron deficient anemia?
dietary lack of iron or decreased absorption (poor diet, cow’s milk in infants)
impaired absorption (sprue, partial gastrectomy-acid increases solubility and uptake)
chronic blood or iron loss (tumor, ulcer, menometrorrhagia, extreme distance running)
What does the blood panel look like in someone with iron deficient anemia?
anisocytosis, poikilocytosis, microcytosis, hypochromia
MCV decreased (microcytosis)
MCH decreased
MCHC decreased (hypochromia)
RBC decreased
Reticulocyte count decreased as erythropoiesis decreases
Histologically, when should iron deficient anemia be suspected?
hypochromic microcytic anemia with elevated RDW but no consistent shape changes in RBC
The laboratory evaluation of enmial begins with what?
then, the anemia is catagorized how?
Then what is is done to confirm the diagnosis?
How are the microcytic anemias separated?
How is iron deficiency anemia separated from beta thal.?
a complete blood count and reticulocyte index
as microcytic, macrocytic, or normocytic based on MCV with or without reticulocytosis
peripheral smear
serum iron level, TIBC, and serum ferritin levels
Which anemias have an elevated reticulocyte count?
sickle cell anemia
G6PD def.
Heriditary spherocytosis
autoimmune hemolytic
paroxysmal nocturnal hemoglobinuria
What is marked erythroid hyperplasia?
anemia caused by increased red cell loss or reduced red cell life span generating elevated reticulocyte counts in the peripheral blood and erythroid hyperplasia in the bone marrow
When do you see nucleated RBCs?
Compensatory Erythropoiesis
- severe anemia
- chronic hypoexmia
Hyposplenism, Asplenia
- sickle cell
- traumatic splenectomy
When do you see magaloblastic hyperplasia?
folate or b12 deficiencies
bone marrow is hypercelluar with giant metamyelocytes and band forms with hypersegmented neutrophils and macrocytic ovalocytes (MCV high)
What anemias have an elevated MCV (macrocytic)
megaloblastic anemia
- B12 def.
- Folate def.
Alcoholic Liver Disease
Hypocellular bone marrow indicates what?
What disease has this?
reduced hematopoiesis
aplastic anemia (pancytopenia of all cell lines)
What anemias/diseases have low reticulocyte counts?
Marrow failure
aplastic anemia
myelofibrosis
leukemia/metastasis
renal failure
anemia of chronic disease
Marrow replacement/invasion an occur by what?
tumor
infection
myelofibrosis
myeloproliferative disorder
What is extramedullary hematopoeisis?
hematopoiesis occuring in organs outside of the bone marrow, frequently in the spleen, liver and LN
normal during fetal development
In what anemias/diseases does extramedullary hematopoiesis function as a compensatory mechanism for abnormal hematopoiesis?
severe chronic anemia of thalassemia, sickle cell, B12, or folate def.
stem cell failure (toxic aplastic anemia)
infection (parvovirus)
malignant tranformation and replacement (lymphoma)
What anemias are microcytic (low MCV)
iron def.
thalassemia
anemia of chronic disease
sideroblastic anemia
What are schistocytes indicative of?
microangiopathic hemolytic anemia (DIC, TTP/HUS)
thrombocytopenia with anemia
What are “bite” cells and Heinz bodies associated with?
G6PD def.
oxidative stress, cross binding and protein deposition
What are sickled RBCs associated with?
Sickle cell anemia
deformed erythrocytes due to polymerized abnormal hgb S
homozygous abnormal hb SS
What are spherical RBCs/Spherocytes associated with?
Spherocytosis
What is the normal WBC?
What white cell makes up the most white cells?
what lymphocyte makes up the most lymphocytes?
4.8-10.8 (x10^3/uL)
neutrophils are the most
T cells
What are causes of neutrophilia
acute bacterial infection
medications (glucocorticoids, catecholamines)
cigarette smoking
various types of physical stress
myeloproliferative neoplasms/leukemia
What is left shift?
(he said this slide was important)
increased immature leukocytes, especially band forms
What is neutrophilia, especially neutrophilia with acute left shift, is associated with what?
acute bacterial infections
What is toxic granulation?
dark course granules within neutrophils, especially in inflammatory conditions
How do you tell the difference between band cells and metamyelocyte?
band cells have horseshoe nuclei
metamyelocytes are juvenile granulocytes and look kidney-ish
what is a leukemoid reaction?
- WBC count is greater than 50,000/microL, with increased neutrophils without evidence of leukemia
- due to infection, drugs, carcinoma (paraneoplastic IL-6)
- bone marrow would show complete maturation without increased blasts
- leukocyte Alkaline phosphatase is ELEVATED
What should always be on top of the DDx list when the WBC is over 50,000?
leukemic or lymphoproliferative process
What is Chronic Myelogenous Leukemia?
- WBC count around 100,000
- insidious disease process, typically of adults
- high WBC, progressive increase in blasts
- starts in chronic phase, then accelerated phase has increase of 10-19% blasts, then blast phase as over 20% blasts in blood or bone marrow
What is acute myeloid leukemia?
- occurs at all ages, peaks over 60
- accumulation of immature myeloid blasts (>20%) in the bone marrow
- can present with anemia, thrombocytopenia, and neutropenia due to bone marrow crowding
What are some causes of inadequate granulopoiesis?
(leads to neutropenia)
- suppression of granulocytic precursors (drugs/toxins)
- suppression of hematopoietic stem cells (aplastic anemia, marrow replacement/invasion)
- ineffective hematopoiesis (neutropenia seen with B12/folate deficient anemias)
What can cause increased destruction/sequestration leading to neutropenia
- immunologically mediated injury to neutrophils (autoimmune, lupus)
- splenomegaly (portal HTN, leads to mild neutropenia)
- increased peripheral utilization (overwhelming bacterial or fungal infection)
What are some benign causes of absolute lymphocytosis?
EBV causing Mono
CMV
Pertussis
Toxoplasmosis
drug-induced
RA
hyperthyroidism
What are the findings in chronic lymphocytic leukemia?
What are the findings in acute lymphoblastic leukemia?
older adults, >5000 ALC, lymphadenopathy, hepatosplenomegaly
children, numerous blasts on the peripheral smear or bone marrow
test with cytometry
What are some additional causes of leukocytosis?
Eosinophilic leukocytosis-allergic conditions and parasites
basophilic leukocytosis-rare, can be seen in leukemia
monocytosis-atypical bacterial infections, autoimmune disease
Briefly describe platelet function in primary hemostasis
- platelets from a primary plug that initially seals vascular defects and allows coagulation factors to bind
- platelets bind via Gp1b von Willebrand factor on exposed collagen
- platelets change shape and release ADP and thromboxane A2
- ADP and TxA2 cause more platelet activation and allow GpIIb-IIIa receptor affinity to fibrinogen to increase causing aggregation of platelets via fibrinogen
What is the physiologic range for platelets?
150,000-450,000/uL
What is thrombocytopenia
mucocutaneous bleeding occurs with low platelets
Plts <100K are high risk for surgery and should be avoided
Plts <50k will cause surgical bleeding
Plts <20k will cause severe bleeding, spontaneous hemorrhage and IC bleeds
Increased platelet destruction can lead to thrombocytopenia. What can lead to increased platelet destruction?
idiopathic thrombocytopenic purpura
idiopathic or secondary autoimmune destruction {(SLE, HIV)
Drug induced, Heparin induced
disseminated intravascular coagulation
thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
hiv associated thrombocytopenia
What are some causes of decreased production of platelets that can also lead to thrombocytopenia?
bone marrow replacement due to tumor
liver diseases reducing TPO production
BONUS:
Sequestration of platelets can lead to decrease. What causes that? Hypersplenism!
