Erythrocytes

Hematology

Study of blood and components

Hematopoiesis

Process by which pluripotent stem cells in bone marrow differentiate into mature blood cells

Bone marrow

Primary site of hematopoiesis

Peripheral blood

Circulating blood in vasculature

Mostly has mature cells

Myeloid cell lineage

Erythrocytes, platelets (thrombocytes), granulocytes (neutrophils [not cell specific], basophils, eosinophils), monocytes → macrophages

Lymphoid cell linege

B lymphocytes (antibody), T lymphocytes (cellular immunity - T helper and Cytotoxic T cells), natural killer cells

RBCs

Biconcave shape, no nucleus, contains hemoglobin

Erythropoiesis

Production of erythrocyte or RBCs from myeloid progenitors in the bone marrow

Reticulocytes

Immature RBCs released into peripheral circulation → Matures within 24 hrs

Erythropoietin (EPO)

Hormone produced by the kidneys in response to low O2

Stimulates erythropoiesis

Regulatory mechanism of Erythropoiesis

1. Low O2 tension

2. Hypoxia sensed by kidney

3. EPO secreted by renal capillaries

4. Erythropoiesis stimulated in bone marrow

5. Increased RBC production (more O2 carrying capacity)

6. Increased O2 delivery (negative feedback loop)

7. EPO secretion decreased

Diabetes Mellitus

Chronic hyperglycemia causes glycation of Hb

Above 6.5% is diagnostic

HbA1c

Blood glucose levels, sugar sticks to Hb in RBC

RBC lives for 120 days 

Effect of renal disease on erythropoesis

EPO secretion decreases → Decreased RBC count

O2 carrying capacity down

Effect of athletic doping on erythropoiesis

Take EPO → Increased RBC production → More O2 carrying capacity

Senescence

Death of RBC

Senescence mechanism

1. RBC breakdown in spleen

2. Hb broken down into heme, globin, and porphyrin ring

3. Bilirubin solubilized in spleen by albumin → Transported to liver (unconjugated bilirubin)

4. Bilirubin released by albumin and enters hepatocytes

5. Bilirubin glucuronidated by glucuronyl transferase (conjugated bilirubin)

6. Conjugated bilirubin excreted → Bile duct or intestine

What type of bilirubin would be elevated in a patient with HbS?

Sickle cells lysing in circulation

Unconjugated bilirubin because of too many lysed cells and overwhelming of liver

Pre-hepatic jaundice

High concentration of unconjugated bilirubin

Wilson Disease, HbS

Intra-hepatic jaundice

High concentration of conjugated bilirubin

Hepatitis, liver disorders

Post-hepatic jaundice

High concentration of conjugated bilirubin

Gall stones (occlude duct), pancreatic cancer

Sickle cell anemia

Most common inherited hemolytic disease
Glu → Val, HbS polymerizes under low O2 causing RBC sickling
Endemic in areas with malaria because sickle cell inhibits reproduction of parasite

HbS sickling stimulated by…

Low O2 (pulmonary disease, low atm oxygen, exercise), Low temp, dehydration

Major pathological consequences of HbS

Poor O2 transport and delivery → Fatigue
Vascular occlusion → Ischemia
Rupture RBCs

Vaso-occlusion

Hemoglobin self assembles into filaments → Sickling and rupture

Ocular presentations of HbS

Conjunctival ‘comma sign’ (blood vessel that looks like a comma) with boxcarring (wavy blood vessels)

Non-traumatic hyphema

Salmon patch

Black sunburst lesions

Sickle cell retinopathy

Retinal detachment

Severe hemolysis causes…

Jaundice/icterus

Sickle cell pathogenesis - Acute severe

1. Low O2, temp, dehydration

2. RBC lyse and elongate

a. Hemolysis and vaso-occlusion

Sickle cell pathogenesis - Severe

1. Chronic or hyperacute O2, temp, dehydration

2. Hemolysis and vaso-occlusion (severity difference)

a. Ischemia

b. Necrosis

c. Hypoxia

d. Neovascularization

e. Hemorrhages

f. Inflammation and repair

VEGF

Vascular endothelial growth factor

Stimulates the creation of new blood vessels

Stages of HbS

1. Occlusion of arteries/arterioles in periphery

2. Neovascularization

3. Sea fan

4. Hemorrhages (fibrovascular tissue from scarring)

5. Retinal detachment

If there is ischemia…

There is always VEGF → Always a risk for neovascularization → Risk for hemorrhaging → Risk for scarring → Risk for retinal detachment