HISTO <3 Blood hematopoeisis

Plasma vs serum: what is the key distinction?

Plasma contains fibrinogen, while serum lacks fibrinogen after clotting

Why does serum lack fibrinogen?

Clotting converts fibrinogen into fibrin, removing it from the liquid fraction

After anticoagulated blood is centrifuged, what are the 3 layers?

Bottom: RBC hematocrit, middle: buffy coat, top: plasma

What cells make up the buffy coat?

Leukocytes and platelets

Why is the center of a normal RBC pale on a blood smear?

Its biconcave shape makes the center thinner and more translucent

Why is the RBC biconcave shape physiologically advantageous?

It increases surface area for gas exchange and facilitates deformability

How can an ~8-µm RBC traverse a ~5-µm capillary?

Its flexible cytoskeleton allows marked deformation and folding

What is the normal circulating lifespan of an erythrocyte?

Approximately 120 days

Why can't a mature RBC undergo mitosis?

It lacks a nucleus and organelles

What makes RBC cytoplasm strongly eosinophilic?

Its high hemoglobin concentration

Where does hematopoiesis occur after birth?

Red bone marrow

What are the 3 major prenatal hematopoietic phases in order?

Yolk sac → liver → bone marrow

Which hematopoietic site predominates during the 1st trimester?

Yolk sac

Which hematopoietic site predominates during the 2nd trimester?

Liver

Which hematopoietic site predominates during the 3rd trimester?

Bone marrow

All circulating blood cells ultimately arise from what cell?

Hematopoietic stem cell (HSC)

Why does Moffett prefer "hematopoietic stem cell" over "pluripotent stem cell"?

HSCs are multipotent for blood lineages, not truly pluripotent for all tissues

What 2 major progenitors arise from an HSC?

Common lymphoid progenitor (CLP) and common myeloid progenitor (CMP)

Which cells arise from the common lymphoid progenitor?

T cells, B cells, and natural killer cells

What major cells arise from the common myeloid progenitor?

RBCs, platelets, granulocytes, monocytes, and dendritic cells

A cell can become an RBC or platelet. What progenitor is it?

Megakaryocyte-erythroid progenitor (MEP), a bipotent progenitor

What determines which lineage a hematopoietic progenitor enters?

Growth-factor signaling drives lineage commitment and maturation

Which hormone drives erythroid development?

Erythropoietin (EPO)

Which hormone drives megakaryocyte/platelet development?

Thrombopoietin (TPO)

When is an erythroid precursor committed specifically to the RBC lineage?

At the erythroid colony-forming unit/erythrocyte progenitor stage

About how long does it take to progress from a committed erythroid progenitor to a mature RBC?

Approximately 8 days in Moffett's lecture

During erythropoiesis, what happens to overall cell size?

It progressively decreases

During erythropoiesis, what happens to nuclear size?

It progressively decreases until the nucleus is extruded

Why does erythroid cytoplasm become more eosinophilic with maturation?

Increasing hemoglobin synthesis overwhelms the earlier basophilia

Why is an early erythroblast strongly basophilic?

Abundant ribosomal RNA used for protein and hemoglobin synthesis

Why is a polychromatophilic erythroblast both blue and pink?

It contains basophilic ribosomes plus increasing eosinophilic hemoglobin

What is the first anucleate stage of erythroid maturation?

Reticulocyte

How does an erythroblast lose its nucleus?

Nuclear extrusion

Why can a reticulocyte no longer divide?

It has already extruded its nucleus

What remnants distinguish a reticulocyte from a mature RBC?

Residual polyribosomes, organelles, and filamentous material

What happens as a reticulocyte becomes a mature erythrocyte?

Residual organelles and ribosomes disappear and the cell becomes slightly smaller

Reticulocyte vs reticular cell: what's the distinction?

Reticulocyte = immature RBC, reticular cell = connective-tissue cell producing reticular fibers

An anemic patient has a high reticulocyte count. What does it imply?

The marrow is responding appropriately, suggesting peripheral RBC loss or destruction such as bleeding or hemolysis

An anemic patient has a low reticulocyte count. What does it imply?

Inadequate marrow RBC production rather than an appropriate regenerative response

Where is erythropoietin produced primarily?

Kidneys

What physiologic stimulus increases renal EPO production?

Hypoxia

How does EPO support early erythroid precursors?

It is anti-apoptotic, allowing more erythroid precursors to survive

How does EPO affect later erythroid development?

It promotes proliferation and maturation of erythroid precursors

Why can chronic kidney disease cause anemia?

Damaged kidneys produce less EPO → reduced erythropoiesis

Why can recombinant EPO help CKD-associated anemia?

It replaces deficient EPO signaling and stimulates RBC production

Why might chemotherapy cause anemia?

It damages rapidly proliferating marrow precursors, reducing RBC production

How can EPO blood doping improve athletic performance?

More RBCs increase blood O₂-carrying capacity and muscle oxygen delivery

ABO blood type is determined by what RBC structures?

Surface glycoprotein antigens A and/or B

Type A blood: RBC antigen and plasma antibody?

A antigen, anti-B antibody

Type B blood: RBC antigen and plasma antibody?

B antigen, anti-A antibody

Type AB blood: RBC antigens and plasma antibodies?

A + B antigens, neither anti-A nor anti-B

Type O blood: RBC antigens and plasma antibodies?

Neither A nor B antigen, both anti-A and anti-B antibodies

For packed RBC transfusion, why is type O the universal ABO donor?

Its RBCs lack A and B antigens targeted by recipient antibodies

For packed RBC transfusion, why is AB the universal ABO recipient?

AB plasma lacks anti-A and anti-B antibodies

Why do packed RBC transfusion rules differ from whole-blood rules?

Packed RBC rules focus on donor RBC antigens, while whole blood also transfers donor plasma antibodies

What does Rh-positive mean?

Rh/D antigen is present on the RBC surface

What does Rh-negative mean?

Rh/D antigen is absent from the RBC surface

Do Rh-negative people normally have anti-D antibodies without exposure?

No, anti-D typically develops only after exposure to Rh-positive RBCs

Why is a first Rh-positive pregnancy often less affected in an Rh-negative mother?

Maternal sensitization and anti-D production usually require prior fetal RBC exposure

Why can a later Rh-positive pregnancy be dangerous after maternal sensitization?

Maternal anti-D can cross the placenta and attack fetal Rh-positive RBCs

What prevents Rh sensitization in an Rh-negative mother?

Rh immune globulin (RhoGAM) prophylaxis

What does agglutination with anti-A reagent indicate during blood typing?

The patient's RBCs express A antigen

What does agglutination with anti-B reagent indicate?

The patient's RBCs express B antigen

Agglutination with anti-A and anti-B indicates what ABO type?

AB

No agglutination with anti-A or anti-B indicates what ABO type?

O

What does mean corpuscular volume (MCV) classify?

RBC size as microcytic, normocytic, or macrocytic

What is the most common cause of microcytic anemia in this lecture?

Iron deficiency

Why are RBCs pale in iron-deficiency anemia?

Impaired hemoglobin synthesis causes hypochromia and increased central pallor

Microcytic + pale RBCs + increased central pallor suggests what?

Iron-deficiency anemia

Normocytic anemia + high reticulocytes suggests what broad mechanism?

Peripheral RBC loss or destruction with an appropriate marrow response

What causes of normocytic anemia with high reticulocytes does Moffett mention?

Acute blood loss and sickle cell anemia

Normocytic anemia + low reticulocytes suggests what broad mechanism?

Insufficient RBC production

What causes of low-reticulocyte normocytic anemia does Moffett mention?

EPO deficiency, bone marrow failure, and leukemia

What is the major cellular problem in megaloblastic/macrocytic anemia?

Cell division lags behind cytoplasmic development, producing oversized RBC precursors and cells

Which deficiency is emphasized as a cause of macrocytic/megaloblastic anemia?

Vitamin B12 deficiency

What other major cause of macrocytosis does Moffett mention?

Alcohol use disorder

What are platelets structurally?

Cytoplasmic fragments derived from megakaryocytes, not complete cells

What is the approximate platelet lifespan?

About 10 days

What is the principal function of platelets?

Hemostasis by limiting bleeding and helping form clots

What cell produces platelets?

Megakaryocyte

How many platelets can a mature megakaryocyte release?

Thousands of cytoplasmic platelet fragments

How is a megakaryocyte recognized histologically?

Very large marrow cell with a complex multilobed nucleus

What 4 platelet zones does Moffett describe?

Peripheral, structural, organelle, and membrane zones

What is important about the platelet peripheral zone?

It contains membrane and glycocalyx components involved in coagulation

What is the platelet structural zone composed mainly of?

Microtubules and actin that maintain the platelet's disk shape

What does the platelet organelle zone contain?

The platelet's organelles and granule-containing central region

What structures characterize the platelet membrane zone?

Open canalicular system plus dense tubular system involved in Ca²⁺ handling

How do platelets appear relative to RBCs on a smear?

Much smaller, more basophilic, with hazy or indeterminate borders

What initially triggers platelet adhesion during vessel injury?

Vessel damage exposes underlying connective tissue to circulating platelets

What platelet-released mediator causes vasoconstriction?

Serotonin

What mediators recruit and activate additional platelets in Moffett's lecture?

ADP and thromboxane

How does aspirin interfere with platelet function?

It inhibits thromboxane production, impairing normal platelet recruitment and aggregation

What forms the primary hemostatic plug?

Aggregated platelets themselves

What forms the secondary hemostatic plug?

Fibrin stabilizing the platelet plug

What platelet product helps repair damaged endothelium?

Platelet-derived growth factor (PDGF)

What plasma protein is converted into fibrin during clot formation?

Fibrinogen

Where is fibrinogen synthesized?

Hepatocytes

What dissolves a clot after endothelial repair?

tPA activates plasminogen → plasmin, which promotes clot breakdown

Thrombus vs embolus?

Thrombus = stationary intravascular clot, embolus = detached traveling material or clot

Why is an embolus clinically dangerous?

It can travel and obstruct a distant blood vessel