Hematopoietics: RBC and Platelets Flashcards
Hematopoietic Stem Cells (HSC)
the most common origin of the formed elements of blood- red cels, granulocytes, monocytes, platelets, and lymphocytes
Hematopoiesis
the development process of blood
The most active marrow in adults?
vertebrae, sternum, and ribs
the most active marrow in children?
long bones
composition of blood
5.5L; 90% water and 10% solutes
Plasma
50-55% of blood volume; contains organic and inorganic elements
Formed Elements
Blood cells and Platelets (~45%)
Serum
Part of blood which is similar in composition with plasma but exclude clotting factors of blood
Red Blood Cells
Transports oxygen and carbon dioxide; lifespan 120 days
Neutrophils
Phagocytize bacteria; lifespan 6 hr - few days
Eosinophils
Phagocytize antigen antibody complex; attacks parasites; lifespan 8-12 days
Basophils
Releases histamine during inflammation; lifespan a few hours- a few days
Monocyte
Phagocytize bacteria, dead cells, and cellular debris; lifespan of many months
Lymphocyte
Involved in immune protection, either attacking cells directly or producing antibodies; lifespan of many years
Platelets
Key roles in blood clotting; lifespan of 5-10 days
Anemia
A reduction in the oxygen transporting capacity of blood, resulting from a decrease in the red cell mass to subnormal levels
Diagnostic Features of Anemia
- Decreased Hematocrit
- Decreased Hemoglobin Concentration
- Correlate with the red cell mass except when there are changes in plasma volume caused by fluid retention or dehydration
Clinical Features of Anemia
- Pale appearance
- Weakness
- Malaise
- Easy fatiguability
- Low O2: dyspnea on mild exertion. Hypoxia can cause fatty change in liver, myocardium, and kidney
Microcytic anemia
Iron deficiency
EX: thalassemia
Macrocytic anemia
Folate or Vitamin B12 deficiency
Normocytic anemia
Abnormal shapes
-hereditary spherocytosis, sickle cell disease
Acute Blood loss anemia
> 20% blood loss, hypovolemic shock
- if patient survives: hemodilution
- normocytic; normochromic anemia
Chronic Blood loss anemia
Iron store depletion
-i.e menstruation
Hemolytic Anemia Features
- A shortened red cell life span below the normal 120 days
- Increased Erythropoietin: Erythroid Hyperplasia and Reticulocytosis
- Accumulation of hemoglobin degradation productd
Extravascular Hemolysis
- Caused by defects that increase the destruction of RBCs by splenic macrophages
- Degradation of hemoglobin: hyperbilirubinemia and Jaundice
- Splenomegaly from “work hyperplasia” of pahgocytes
- Cholelithiasis
Intravascular Hemolysis
- Severe Injury: red cells burst within circulation
- result from either mechanical force (defective heart valve) or biochemical or physical agents (fixation of complement)
Consequences of Intravascular Hemolysis
Hemoglobinemia, Hemoglobinuria, and Hemosiderinuria
-Iron deficiency
Hereditary Spherocytosis
- Mutations resulting in insufficient membrane skeletal components (spectrin, anykyrin) resulting in reduced stability of RBC membrane
- partial Splenectomy can correct anemia
Clinical Features of Hereditary Spherocytosis
- Anemia, Splenomegaly, and Jaundice
- Spherical shape- osmotic fragility
- Generally stable course: parvovirus B19 infection which leads to aplastic crisis, leads to rapid worsening of the anemia and will need blood transfusions
G-6-PD deficiency
- Reduced glutathione (GSH) required to neutralize compounds such as H2O2
- X linked recessive (more affected males)
- 2-3 days after drug expsoure leads to Hemolysis
- GSH -> oxidants “attack” of Hb -> Hb denatures and precipitates -> Heinz bodies -> intravascular hemolysis
- other cells with lesser damage -> extravascular hemolysis
Causes G-6-PD deficiency
- Infectious (viral heaptitis, pneumonia)
- Antimalarials (primaquine), sulfonamides, nitrofuratoin, phenacetin, aspirin, and vitamin K derivatives (fava beans)
- Oxidants cause both IV an EV hemolysis in G6PD deficient people
The reaction that results in oxidative injury and hemolysis
G6PD -> oxidative injury -> hemolysis
Sickle Cell Disease
Glutamate –> Valine
-Chronic hemolysis, microvascular occlusions, and tissue damage
Clinical features of Sickle cell disease
- Moderately severe hemolytic anemia: Reticulocytosis, Hyperbilirubinemia, irreversibly sickled cells
- Vaso- occlusive crisis (pain in bones, lungs, liver, and brain)
- acute chest syndrome, priapism, stroke. retinopathy/blindness, “autosplenectomy”
- Chronic hypoxia
- altered splenic function
SCD: Protective factor and rate and degree of sickling
-Protection against falciparum malaria
Rate and Degree of Sickling:
-Mean cell hemoglobin concentration (MCHC)
-Intracellular pH
-Transit time of Red Cells through microvascular beds
Vaso-occlusive crisis
Pain crisis (bones, lungs, liver, brain)
Autosplenectomy
A negative outcome of disease and occurs when a disease damages the spleen to such an extent that it becomes shrunken and non functional
Thalassemia
It is caused by inherited mutations that decrease the synthesis of either alpha or beta globin chains that compose adult hemoglobin
Thalassemia mechanism
- Decreased HbA formation -> microcytic, hypochromic red cells
- accumulation of unpaired alpha globin chains -> toxic precipitates that severely damage membranes of red cells and erythroid precursors -> ineffective erythropoiesis
Clinical features of Thalassemia
- manifests 6-9 months after birth
- PBS: microcytic, hypochromic RBCs with anisocytosis (variable size)
- Extramedullary hematopoiesis
- cause of death from cardiac disease from iron overload and secondary hemochromatosis
Balance between hepcidin and iron
Decreased Hepcidin means theres an Overload of Iron from excessive absorption of dietary iron
Iron deficiency Anemia
Most common nutritional disorder in the world
- Dietary lack
- Impaired absorption
- Increased Requirement
- Chronic blood loss
Features of Iron Deficient Anemia
- Severe cases: weakness, listlessness, and pallor
- Chronic Anemia: Abnormalities of fingernails (thinning, flattening, and spooning)
Transferrin
Synthesized in the liver and transports iron; delivers iron to cells, including erythroid precursors
DMT 1 (Divalent Metal Transporter 1)
When ferrous iron is reduced by ferric reductase, DMT 1 transports it across the apical membrane
Ferroportin
Moves iron from the cytoplasm to plasma across the basolateral membrane
Diagnostic Criteria for Iron Deficiency
- Hypochromic and Microcytic Anemia
- Low serum ferritin and iron levels
- Low transferrin saturation
- increased total iron binding capacity
- response to iron therapy
Causes of Vitamin B12 deficiency
- Achlorhydria (impairs vitamin B12 release from R binders)
- Gastrectomy (causes loss of IF)
- Ileal resection (or diffuse ileal disease)
- Malabsorption syndromes (increased requirements)
Clinical Features of B12 deficiency
- Easy fatigability, dyspnea, CHF
- ineffective Erythropoiesis (mild jaundice)
- Megaloblastic changes (Beefy red tongue)
- increased risk of development of gastric carcinoma
- Neurologic lesions: symmetric numbness, tingling, burning feeling in feet or hands, unsteady gait and loss of position
Folate Deficiency
- Inadequate intake (chronic alcoholics)
- Malabsorption syndromes (Sprue)
- Increased demand (pregnancy, infancy, disseminated cancer)
- folate antagonists
- boiling, steaming, or frying greens for 5-10 minutes destroys 95% of folate
- Onset: insidious; associated with weakness and easy fatigability
- NO neurological abnormalities
Sources of folate
Green vegetables (lettuce, spinach, etc)
Causes of Anemia of Chronic Diseases
- Chronic microbial infections (osteomyelitis, IE, and lung abcess)
- Chronic Immune Disorders (rheumatoid arthritis)
- Neoplasms
- high levels of hepcidin
- chronic inflammation - decreases EPO synthesis in kidney which decreases RBC
- Red cells may be slightly hypochromic and microcytic
Aplastic Anemia
- Multipotent myeloid stem cell suppression -> chronic primary heamtopoietic failure leads to pancytopenia (anemia, neutropenia, and thrombocytopenia)
- Idiopathic
- chemicals and drugs, irradiation, viral infections, telomerase mutations
Aplastic Anemia Pathogenesis
Extrinsic: Immune mediated suppression of marrow progenitors
Intrinsic: Abnormality of stem cells
Aplastic Anemia Clinical Features
- Pancytopenia
- Anemia (progressive weakness, pallor, dyspnea)
- Thrombocytopenia (Petechiae and ecchymosis)
- Neutropenia (sudden onset of chills, fever, prostration)
- Reticulocytopenia
- Splenomegaly
Polycythemia
Abnormally high red cell count which increases hemoglobin level
Relative Polycythemia
- Dehydration
- Excessive Use of Diuretics
Absolute Polycythemia
- 1st degree (intrinsic abnormality of HSCs)
- 2nd degree (progenitors are responding to increased levels of erythropoietin)
Most common type of polycythemia
Polycythemia Vera
-mutations resulting in erythropoietin independent growth of red cell progenitors
Thrombocytopenia
- <100,000/uL: causes bleeding
- 20,000 to 50,000/uL: aggravate post traumatic bleeding
- less than 20,000/ uL: spontaneous (non traumatic) bleeding
Causes of Thrombocytopenia
- Decreased platelet production
- Decreased platelet survival
- Sequestration (too much accumulation in spleen)
- Dilution
Chronic Immune Thrombocytopenic Purpura (ITP)
- Caused by autoantibody mediated destruction of platelets
- Markedly improved by splenectomy (spleen in a major site of removal of opsonized platelets, source of autoantibodies)
Clinical features of Chronic Immune Thrombocytopenic Purpura
- Most commonly in adult women <40 yrs
- bleeding into skin and mucosa
- H/O easy bruising, nosebleeds, gum bleeding, hemorrhages into soft tissues from minor trauma
- Manifests first with melena, hematuria, or excessive menstrual flow
