Third lectureThird lecture

Composition of the bloodComposition of the blood

1-RBCs (erythrocytes).1-RBCs (erythrocytes).

2-WBCs (leukocytes).2-WBCs (leukocytes). Granulocytes.Granulocytes. A granulocytes.A granulocytes.

3-Thrombocytes 3-Thrombocytes (Platelets).(Platelets).

1-Erythrocytes1-Erythrocytes (RBCs)(RBCs) 8 8 m in diameter. m in diameter. 2.7 2.7 m thick.m thick. volume ~ 90 volume ~ 90 mm33. . area ~ 160 area ~ 160 mm2.2.

Biconcave disc.Biconcave disc. surface area.surface area. efficiency for efficiency for

diffusion of O2 & diffusion of O2 & CO2.CO2.

11--ErythrocytesErythrocytes

StructureStructure Plasma membranePlasma membraneCytoplasmCytoplasm

Hemoglobin Hemoglobin Binds OBinds O22 & CO & CO22

No nucleus or No nucleus or organellesorganelles

1-Erythrocytes1-Erythrocytes

Flexible.Flexible. Elastic.Elastic. Life span 100-120 day.Life span 100-120 day. Originate in bone marrow.Originate in bone marrow.

Erythroblasts

Reticulocytes

Become progressively smaller, form haemoglobin, lose nucleus

Released into circulation, mature over following 24 hours - lose mitochondria and ability to synthesise protein (haemoglobin)

Erythrocyte (RBCs)

No mitochondria - utilise glycolytic pathway for energy

Regul a

ted b

y e

r yth

r opoie

t in

Formation of RBCs

Fate of red blood cells

Life span in blood stream is ~120 days.

Senescent RBCs are phagocytosed

and/or lysed. Normally, lysis occurs extravascularly

in the reticuloendothelial system

subsequent to RBC phagocytosis. Lysis can also occur intravascularly.

Extravascular Destruction of RBCsExtravascular Destruction of RBCs

Liver,Bone marrow, & Spleen.

Hemoglobin

Globin

Amino acids

Amino acid pool

Heme Bilirubin

Fe2+

Excreted

Phagocytosis & Lysis

Hemolysis

Hemolysis

In normal adults this results in a daily load

of 250-300 mg of bilirubin. Normal plasma concentrations are less

then 1 mg/100ml. Hydrophobic – transported by albumin to

the liver for further metabolism prior to its

excretion.

Degradation of heme

Normal bilirubin metabolismNormal bilirubin metabolism

Uptake of bilirubin by the liver is mediated by a carrier protein.

On the smooth ER, bilirubin is conjugated with glucoronic acid, xylose, or ribose.

Glucoronic acid is the major conjugate - catalyzed by UDP glucuronyl tranferase.

“Conjugated” bilirubin is water soluble and is secreted by the hepatocytes into the biliary canaliculi.

Normal bilirubin Normal bilirubin metabolismmetabolism

Converted to stercobilinogen (urobilinogen) (colorless) by bacteria in the gut.

Oxidized to stercobilin which is colored.

Excreted in feces.

Some stercobilin may be re-adsorbed by the gut and re-excreted by either liver or kidney.

HyperbilirubinemiaHyperbilirubinemia

Increased plasma concentrations of bilirubin (> 3 mg/100mL) occurs when there is an imbalance between its production and excretion.

Recognized clinically as jaundice.

Handling of free Hemoglobin Haptoglobin:Haptoglobin:

hemoglobin-haptoglobin complex is hemoglobin-haptoglobin complex is readily metabolized in the liver and spleen readily metabolized in the liver and spleen forming an iron-globin complex and forming an iron-globin complex and bilirubin. bilirubin.

This prevents loss of iron in urine.This prevents loss of iron in urine.

Hemopexin:Hemopexin:

binds free heme. The heme-hemopexin binds free heme. The heme-hemopexin complex is taken up by the liver and the complex is taken up by the liver and the iron is stored bound to ferritin.iron is stored bound to ferritin.

Methemalbumin:Methemalbumin:

complex of oxidized heme and complex of oxidized heme and albumin. albumin.

Purposes:Purposes:

1. Scavenge iron.1. Scavenge iron.

2. Prevent major iron losses.2. Prevent major iron losses.

3. Free heme is very toxic.3. Free heme is very toxic.

Handling of free hemoglobin