RBC

Hematopoietic stem cells

common mother of formed elements of blood

hematopoiesis

development of blood cells

adults

produce blood cells in vertebrae, sternum, ribs (axial skeleton)

children

produce blood cells in long bones

prenatal

produce blood cells in spleen and liver

extramedullary hematopoiesis

blood made outside of bone marrow

• blood cell production in bone marrow is not sufficient —> other organs take over

• common in anemias, blood cancers

development process of blood cells

• asymmetric cell division

• multipotent —> lymphoid and myeloid progenitor

• lymphoid —> B, T, NK cells

• other cells from myeloid progenitor

• as they differentiate, they become more committed

• CFU —> very specific cell types, become more differentiated

Blood composition

90% water

10% solutes

Plasma

50-55% blood volume

mostly water

organic and inorganic elements (solutes, proteins)

Formed elements

blood cells and platelets (45% of blood volume)

Serum

similar to plasma but no clotting factors

serum = plasma - clotting factors

RBC

120 days lifespan

transport O2 and CO2

Neutrophil

• Granulocyte

• predominant

• 6hrs - few days (one of the shortest living)

• phagocytize bacteria

Eosinophil

• Granulocyte

• 8-12 days

• phagocytize antigen-antibody complex, parasites

Basophil

• Granulocyte

• few hours-few days (one of the shortest living)

• histamine, inflammation

Monocyte

• Agranulocyte

• live for months

• phagocytizes

Lymphocyte

• Agranulocyte

• live for years (longest living)

• immune protection (attack cells or produce Ab)

Platelet

• megakaryocyte precursor

• live for 5-10 days

• blood clotting

Anemia overview

• reduction in O2 transport capacity —> decreased in RBC mass

• tissue hypoxia —> triggers kidneys to release EPO —> reticulocytosis (chronic disease is the only one with low EPO)

• Dx: LOW hematocrit and LOW Hb (careful of overhydration/fluid overload mimic)

• MCV, MCH, MCHC

• General sx: pale, weak, malaise, easily fatigued, dyspnea on mild exertion, headache, dim vision

  • hypoxia —> fatty liver, heart, kidney changes

  • acute blood loss anemia: oliguria, anuria

normal MCV

80-100

(<80 = micro

>100 = macro)

normal mean cell hemoglobin

27-33

(hypochromic = <27, hyperchromic = >33)

normal mean cell Hb concentration

32-36

Acute blood loss

• low blood volume —> cardiac collapse —> shock/death (hypovolemic shock)

• hemodilution (due to administering fluids) —> normocytic/normochromic

• increased reticulocytosis (since O2 and EPO stimulated)

Chronic blood loss

• GI lesions, gyn lesion: Fe stores are depleted

• microcytic and hypochromic (lack of materials)

impaired RBC production

anemia of chronic disease (not bleeding!)

• causes: chronic microbial infections, immune disorders (RA, SLE), cancers

• decreased EPO from inflammation —> low RBC

• chronic conditions cause increased Hepcidin —> iron trapped in cells —> microcytic + hypochromic

Hemolytic anemias

RBC has 1/5 normal life span

high EPO —> reticulocytosis

high Hb degradation products

• extravascular, intravascular (anemias can be either or both)

Extravascular hemolytic anemia

• spleen

• jaundice

• bilirubinemia

• splenomegaly

• gallstones (high in bilirubin) —> cholelithiasis

• macrophages destroy funky RBCs - but recycles Fe so levels are okay

Intravascular hemolytic anemia

• in circulation

• hemosiderinuria (iron loss)

• hemoglobinemia

• hemoglobinuria

• results from mechanical force, chemicals, or complement fixation

Hemolytic anemias genetic conditions

• normocytic

• normochromic

• spherocytosis and G6PD deficiency

Spherocytosis

• spectrin + ankyrin mutation makes spherical RBC

• extravascular (spleen destroys)

• stable unless pt gets Parvo B19 infection in RBC progenitor —> aplasitc crisis and needs transfusion ASAP

• can cure with partial splenectomy

G6PD deficiency

• can’t make glutathione (GSH) antioxidant —> RBC gets hit by ROS (drug, infection, food) —> Hb denatures —> Heinz bodies (intravascular)

• extravascular for less damaged cells

• males are more likely affected (X linked recessive trait)

Hemolytic anemias hemoglobin abnormalities

sickle cell

alpha and beta thalassemias

Sickle cell

• glutamate —> valine: Hb sickles in low O2 —> can’t carry O2

• Plieotrophy: MI, stroke, anemia

• vaso-oclusive crisis: bone, brain, lung, liver (painful)

• severity determined by HCH, rate of movement through microvascular beds, degree of sickling

• Normocytic/normochromic

alpha and beta thalassemias

• no alpha or beta chain —> can’t build Hb…High EPO (want body to make RBCs)

• microcytic/hypochromic

• Anisocytosis (diff RBC sizes)

• Erlenmeyer flask bones (due to increased EPO)

• decreased hepcidin since decreased RBC, so if receiving blood —> hemochromatosis (Fe overload)

• death from: cardiac diseause due to progressive Fe overload (secondary hemochromatosis)

• hepatosplenomegaly (extramedullary hematopoiesis since bone marrow can’t)

Impaired RBC production anemias

• aplastic anemia

• iron deficient anemia

• B12 deficiency

• folate deficiency

Aplastic anemia

• hematopoietic stem cell tissue

• extrinsic: immune mediated marrow progenitor suppression

• intrinsic: genetic stem cell issue

• cause: idiopathic, drugs, radiation, viral infections

• pancytopenia (low RBC, low neutrophils, low platelets)

• reticulocytopenia

• NO splenomegaly

Iron deficiency anemia

• microcytic/hypochromic anemia

• due to: dietary lack, poor absorption, increased requirement, chronic blood loss

• Chronic: koilonychia (nail spooning), pica, fatigue, weakeness, pale

• decreased: serum ferritin, Fe levels, transferrin saturation

• increased EPO, reticulocytes, total Fe binding capacity

• depleted storage iron (ferritin, hemosiderin)

• depleted functional iron (Hb, Mb, enzymes),

B12 deficiency

• megaloblastic anemia

• reversible with folate (B12 is needed to recycle folic acid)

• needed to make DNA, if low, RBC is stuck in S phase and become large

• usually low in vegetarians/vegans

• Pernicious: B12 lack from low intrinsic factor (autoimmune gastritis) so B12 can’t be absorbed

• other causes: low HCl (elderly), gastrectomy, ileal resection, malabsorption (alcoholism)

• Tired, mild jaundice, beefy red tongue, neurologic lesions (numb, tinel, burn, gait issues - can’t be fixed by folate)

Folate deficient

• megaloblastic anemia

• need for DNA so decreased folate —> decreased dTMP —> decreased replication

• causes: low intake, malabsorption, increased demand, folate antagonists

• no neuro deficits

• pt is weak/faigues easy

Low platelets

thrombocytopenia

• <100,000 = bleeding risk

• <20,000 = severe risk

• causes: decreased production, survival, or destroyed by spleen

• Immune thrombocytopenia purpura

immune thrombocytopenia purpura

• platelets are opsonized in spleen

• splenectomy to improve

• excess bleeding: nosebleeds, gums, hemorrhage

• melena (blood in stool)

• hematuria

• excess menstrual flow

Excess RBC

Polycythemia: increased RBC and Hb

• relative: dehydrated to diuretics

• Absolute:

1) intrinsic hematopoietic stem cell abnormality

2) increased EPO from renal cell carcinoma

• most common: polycythemia VERA: EPO-independent RBCs (body makes without signal from EPO) —> type of blood cancer

iron deficiency anemia

MCV: usually low

Retics: low/ inappropriately normal

key lab clue: low ferritin, high TIBC

anemia of inflammation

MCV: normal or low

Retics: low/inappropriately normal

key lab clue: normal/high ferritin, low serum iron, low TIBC

Vitamin B12 deficiency anemia

MCV: usually high

Retics: low/inappropriately normal

Key lab clue: elevated methylmalonic acid

Folate deficiency

MCV: usually high

Retics: low/inappropriately normal

Key lab clue: normal methylmalonic acid

Hemolytic anemia

• MCV: usually normal

• Retics: high

• Key lab clue: high LDH, indirect bilirubin, low haptoglobin

aplastic anemia

MCV: usually normal or high

Retics: low

Key lab clue: pancytopenia and hypocellular marrow