3. Erythrocytes (RBC)

Hematology

Study of Blood Cells

Hematopoiesis

Differentiation of all blood cells

Erythrocytes

RBCs, Transport O2, live 120 days, during time glycated - HbA1c (marker for diabetic activity over 120 days)

Mechanism of Erythropoiesis:

Erythropoiesis: RBC Development in bone marrow; Reticulocytes exit bone marrow and mature to RBC within 24 hours

1. Low O2

2. Hypoxia sensed by kidney releases EPO (erythropoietin)

3. Erythropoiesis stimulated in bone marrow due to EPO

4. Increased RBC production, hence more O2 carrying capacity by blood

5. Increased Oxygen (Negative feedback loop)

Red Blood Cell Maturation

Begins with Hemocytoblast
Proerythroblast
Early Erythroblast
Late Erythroblast
Normoblast
Reticulocyte
Erythrocyte

Mechanism of Senescence of Erythrocytes

1. Older RBCs phagocytosed in spleen (or liver) by macrophages/ Kupfer cells

2. Hb breakdown

3. Bilirubin solubilized by albumin- transported to liver via hepatic portal vein (unconjugated bilirubin)

4. Bilirubin released by albumin- enters hepatocyte

5. Bilirubin conjugaed/glucuronylated by glucuronyl transferase (GT)

6. Conjugated bilirubin excreted into bile duct as part of bile

7. conjugated bilirubin enters intestine and gives stool dark color

Hb: amino acids recycled; hemosiderin recycles Fe+2 to bone marrow; bilirubin excreted through liver into GI

Prehepatic Disease

= Unconjugated Bilirubin

Causes Pale Stool

• Hemolytic disease

  • mostly unconjugated

• Wilson’s Disease

Hepatic Disease

= Unconj/Conj

• Hepatitis and Liver Cancer

  • Mostly conj

    • Decreased bile secretion causing reflux into plasma

Post-Hepatic Disease

= Conjugated; has floating fatty acid

• Occlusion of bile duct

  • Gall stone/ cholelithiasis

  • Cholecystitis

  • Gall bladder surgery

  • Pancreatic cancer

Ocular Presentations of Sickle Cell Anemia

• Conjunctival ‘comma sign’ with boxcarring

• Non-traumatic hyphema

• Black sunburst

• Salmon patch

• Sickle cell retinopathy

Sickle Cell

Most common hemolytic disease
Autosomal recessive= HbS HbS; HbS HbA is heterozygous and has sickle cell trait; HbA HbA = no sickle cell

Sickle Cell Epidemiology

Epidemiology: Endemic in areas with malaria;
Sickled cells kills parasite/inhibits reproduction of parasite P. Falciparum

Sickling stimulated by

Dehydration (typically caused by heat)
At colder temps, vaso-occlusion occurs at the beginning of the capillary and thus sickling
Low O2/ deoxygenation:

• Slowed blood flow from vasodilation (inflammation/sickness)

• Lung Disease

• Anemia

• Low atm Oxygen

• Exercise

• Low pH

Major pathological consequences of Sickle Cell:

Poor O2 transport and delivery => fatigue AND

Vascular occlusion => ischemia and pain

Pathogenesis of Sickle Cell Normal Conditions

Normal O2 delivery

Pathogenesis of Sickle Cell Low O2 Tension

Low O2 tension, low pH (ex. exercise, sickness, cold, stress, lung disease, dehydration, Rx)

Hemolysis = jaundice/icterus if severe

Vaso-occlusive = sickled cells slow or occlude blood flow = severity determines pain

Pathogenesis of Sickle Cell Chronic/Repeated Low O2 Tension

Low pH or severe and sudden onset (sickle cell crisis)
Hemolysis;
Vaso-occlusion:

• Ischemia;

• Infarct/necrosis;

• hypoxia;

• neovascularization;

• hemorrhages;

• inflammation and repair (scar)

Stages of Sickle Cell Retinopathy:

1. Occlusion of arteries/arterioles

2. Neovascularization stimulated by VEGF

3. Sea fan formation

4. Hemorrhage (vision loss); fibrovascular tissue

5. Retinal detachment (vision loss)

Sickle Cell Retinopathy Treatments

Use Anti-VEGF therapy to prevent neovascularization.
Photocoagulation: Use laser to coagulate blood vessels.

The two cell lines of blood

Myeloid and lymphoid

HbA1c

Glycalated hemoglobin; bound to hemoglobin over the 120 days of RBCs’ life cycle; better measure of glucose levels vs blood glucose test

Reticulocyte

Immature RBCs released from the bone marrow

RBC death in the spleen

RBC are less flexible and are phagoctosed by Kupfer cells

Glucuronyl transferase (GT)

enzyme the conjugates bilirubin

Retinal Hemorrhaging (sickle cell)

Fibroblast (smooth muscles) contract to make collagen leading to fibrovascular tissues

Fibroblast and retina detachment

Contraction of smooth muscles leads to retinal detachment

Treatment of sickle cell retinopahy

VEGF inhibitors
Laser coagulation to prevent hemorrhages