T4 red blood cells

site of blood formation - fetus

yolk sac

site of blood formation - before birth

bone marrow, liver & spleen-lymph nodes

site of blood formation - children

bone marrow (flat & long bones)

site of blood formation - adults

bone marrow (flat bones)

mesoblastic period - location

yolk sac

hepatic period - location

liver, spleen, lymph nodes

myeloid period - location

bone marrow

bone marrow functional zones

endosteal, intermediate, central

endosteal zone - components

myeloblasts & promyelocytes

intermediate zone - components

myelocytes & erythroid islands

central zone - components

metamyelocytes, band cells, segmented neutrophils, erythroid islands, megakaryocytes

trend in blood cell maturation

cell shrink, cytoplasm less basophilic (blue), chromatin condense, nucleolus dissapear

RBC - lifespan

120 days

mature RBC - characteristics

central pallor

normoblast

nucleus, ribosomes, RNA, actively produce Hb, eject nucleus as they mature

reticulocyte

nucleus ejected, have residual ribosomal RNA, continue final Hb synthesis

mature RBC

no nucleus, ribosomes, RNA, fully packed with Hb

primary regulator of RBC production

erythropoietin

triggers for increased erythropoiesis

anemia, hemorrhage, high altitude, lung disease, heart failure

anemia - symptoms

fatigue & easy tiring

hormonal stimulators of RBC production

androgens, thyroid hormones, cortisol, growth hormone

RBC - physiological characteristics

permeability, plasticity (flexibility), osmotic fragility, suspension stability

RBC - permeability

semipermeable → O2, CO2, small molecules (urea) can pass

RBC - plasticity

allow to squeeze through narrow capillaries

RBC - osmotic fragility

ability to resist bursting in hypotonic solutions

RBC - suspension stability

erythrocyte sedimentation rate → speed at which RBCs settle in a tube of blood

high ESR = ?

low suspension stability → inflammation

RBC - shape

biconcave disc

RBC membrane - functions

maintains cell shape and osmotic balance, provide receptor sites, ion channels and transporters

RBC membrane - lipids

phospholipid bilayer

cholesterol - high temperature

reduce fluidity and permeability

cholesterol - low temperature

prevents membrane from becoming too rigid

phospholipid enzymes

flippase, floppase, scramblase

flippase

move phospholipids inside (ATP-dependent)

floppase

move phospholipids outside (ATP-dependent)

scramblase

move phospholipids both ways (does not require ATP)

RBC membrane - carbohydrates

act as receptors

RBC membrane - integral proteins

glycophorin, band 3, glut 1

RBC membrane - glycophorin

negative charge to RBC, reduce interaction with other cells

RBC membrane - band 3

anion exchange channel for CO2 transport via bicarbonate exchange

RBC membrane - glut 1

transport glucose

RBC membrane - peripheral proteins

spectrin, actin, ankyrin, protein 4.1, protein 4.2, trophomyosin

RBC membrane - spectrin

forms cytoskeletal network → responsible for biconcave shape

RBC membrane - actin

link spectrin → form membrane skeleton

RBC membrane - ankyrin

connect band 3 with cytoskeleton → forms glycolytic complex → help produce energy

RBC membrane - protein 4.1

stabilize spectrin-actin connection

RBC membrane - 4.2

stabilize band 3 and ankyrin complex

membrane defects RBC disorders

hereditary spherocytosis, hereditary elliptocytosis, southeast asian ovalocytosis

hereditary spherocytosis

defect in ankyrin, spectrin, band 3 or protein 4,2 → RBC becomes spherical & fragile

hereditary elliptocytosis

defect in spectrin dimer formation, spectrin-ankyrin interaction or protein 4,1 → RBC becomes elliptical

southeast asian ovalocytosis

band 3 deletion → oval-shaped RBCs

composition of RBCs

Hb, solids, proteins and structures, mineral content

Hb - function

carry O2 from lungs to tissues & CO2 from tissues to lungs

Hb synthesis - location

bone marrow of developing RBCs

Hb synthesis - key components

1. protoporphyrin synthesis in mitochondria

2. Fe2+ delivered via transferrin from bloodstream

3. globin chain synthesized by ribosomes

heme - structure

cyclin porphyrin ring + central ferrous iron (Fe2+)

hemoproteins - examples

hemoglobin, myoglobin, cytochromes, catalase, peroxidase

heme synthesis - acquired disorder

lead poisoning

heme synthesis - hereditary disorder

acute intermittent porphyria & porphyria cutanea tarda

heme biosynthesis - rate limiting enzyme

ALA synthase

abnormal Hb - symptoms

peripheral cyanosis

Hb qualitative defect - examples

HbS, HbC, HbE

Hb quantitative defect - examples

alpha thalassemia, beta thalassemia, Hb constant spring

RBC - energy production

anaerobic glycolysis

ATP uses

maintain biconcave shape, regulate ion and water balance across membrane, ensure RBC can function w/o consuming O2 they carry

embden-meyerhof pathway - what is it

anaerobic glycolysis to convert glucose → lactate + 2ATP

embden-meyerhof pathway - clinical relevance

pyruvate kinase deficiency & phosphoglucose isomerase deficiency → hemolytic anemia

hexose monophosphate shunt - what is it

pentose phosphate pathway that produce NADPH

hexose monophosphate shunt - function

maintains glutathione in reduced form → protect RBCs from oxidative membrane damage

glutathione

neutralize reactive oxygen species → GSSG (oxidized form)

NADPH

reducing power to convert GSSG back to 2GSH → restore antioxidant capacity

hexose monophosphate shunt - clinical relevance

GDPD deficiency → acute hemolytic anemia

methemoglobin reduction pathway - what is it

reduce Fe3+ back to Fe2+

methemoglobin reduction pathway - cofactor

NADH

rapoport-leubering shunt - what is it

produce 2,3-DPG

rapoport-leubering shunt - function

controls Hb affinity → facilitate O2 release to tissues

extravascular RBC destruction - site

reticuloendothelial system → spleen, liver, bone marrow

extravascular RBC destruction - mechanism

phagocytosis by macrophages

extravascular RBC destruction - common causes

hemolytic anemias, membrane defects, enzyme deficiencies

intravascular RBC destruction - site

bloodstream

intravascular RBC destruction - mechanism

direct rupture (lysis) in circulation

intravascular RBC destruction - common causes

trauma, toxins, immune-mediated lysis

extravascular RBC destruction - lab

increased conjugated bilirubin, increase urine urobilinogen

intravascular RBC destruction - lab

hemoglobinemia, hemoglobinuria, hemosiderinuria, methemalbuminemia

extravascular RBC destruction - blood findings

reticulocytosis, microspherocytes, elliptocytes

anisocytosis

variation in size

macrocyte - what

abnormal large

macrocyte - associated disease

megaloblastic anemia, congenital dyserrythropoietic anemia, myelodysplastic syndrome, acute blood loss, new born

microcyte - what

abnormal small

microcyte - associated disease

iron deficiency anemia, thalassemia, sideroblastic anemia, pyruvate kinase deficiency, inflammation

poikilocytosis

variation in shape

eliptocyte

oval / cigar-shaped

eliptocyte - conditions

megaloblastic anemia, iron deficiency anemia, hereditary elliptocytosis

spherocyte

round, loss of biconcave shape

spherocyte - conditions

autoimmune hemolytic anemia (AIHA), thalassemia, hereditary spherocytosis

sicke cell - conditions

sickle cell anemia (HbS disease)

tear drop cell - conditions

thalassemia, heinz body formation, extramedullary erythropoiesis

schistocyte

fragmented RBC in pieces

schistocyte - conditions

thalassemial, DIC, TTP, hemolytic anemia

horn cell

horn-like projections