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Oxygen and Carbon Dioxide Transport in the Blood

Barbara Dziedzic

Blood Functions• Substance distribution

– Blood transports:• Oxygen and necessary metabolic substrates to the cells of the

body• CO2 and waste products to the lungs and kidneys for

elimination• Hormones from endocrine glands to target organs

• Regulation: – maintaining homeostasis

• regulate pH• adjust body temperature• blood osmotic pressure & blood volume

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Blood Functions• Protection:

– immunity: defense against bacteria, viruses and other agents by leukocytes.

– platelets are responsible for some aspects ofhemostasis – prevention of blood loss.

• Plasma: Liquid fraction of whole blood (extracellular part) – 55%

• Formed elements: Cellular components suspended in the plasma – 45%

• Normal volumes of blood:– Plasma: ~ 2,6 L– Formed elements: ~ 2.4 L– Whole Blood: 4 to 6 L average or 7% to 9% of

the total body weight.

Blood composition and volume

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• RBCs (erythrocytes)• WBCs (leukocytes)

– Granular leukocytes• neutrophils, eosinophils, and basophils

– Agranular leukocytes• lymphocytes and monocytes.

• Platelets (thrombocytes)

Formed elements of blood

Hematocrit

• Hematocrit (Hct) is percentage of total blood volume occupied by red blood cells (RBC) – Normal men – 39 - 49%– Normal women – 33 - 43%– Testosterone stimulates

synthesis of erythropoietin– Low Hct – anemia– High Hct - polycythemia

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Production of Formed Elements• Hematopoiesis : Process of blood cells production.• Hematopoiesis occurs in the red bone marrow• Pluripotential Hematopoietic Stem Cells – from

these cells all types of blood cells are derived. • They give rise to daughter cells, which in turn

differentiate into progenitor stem cells– lymphoid progenitor cell – gives rise to the T and B

lymphocytes.– myeloid progenitor cell – gives rise to the leukocytes,

erythrocytes and platelets.

Hematopoiesis

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Hematopoiesis• Hematopoietic growth factors: EPO, SCF,

GM-CSF, M-CSF, G-CSF and IL-3, IL-1, IL-2, IL-5, IL-6, IL-10, IL-11, LIF– stimulate the proliferation and survival of the

progenitor cells– are essential for survival of the progenitor cells– are responsible for differentiation and

maturation of cells– they act in a paracrine fashion.

Erythropoiesis• Erythropoiesis

– is the production of erythrocytes in the bone marrow

– is dependent on the release of erythropoietin(EPO) from the kidneys

– EPO • increases RBC production 7x (up to 17

million/second) • speeds maturation of RBC

• Hypoxia is a main stimulus for RBC production– Decreased oxygen availability (↓ O2 in air) – ↓ RBCs– ↑ tissue demand for oxygen

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Use and abuse of erythropoietin

• Epoeitin alfa – EPO produced by recombinant DNA technology– is used in the treatment of anemia associated with

renal failure, chronic disease or chemotherapy. – is frequently abused by athletes to increase their

hemoglobin levels and improve performance without having to train at altitude.

• it can lead to dangerously high hematocrit, with risk of blood clotting in arteries due to slow blood flow.

Steps in Erythropoisis

Proerythroblast

BasophilicErythroblast

PolychromatophilicErythroblast

OrthochromatophilicErythroblast

Reticulocyte

Erythrocyte

Early Intermediate Late

• A stem cell is transformed into a committed cell called:proerythroblast

• Proerythroblasts develop into erythroblasts

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Steps in Erythropoisis

Proerythroblast

BasophilicErythroblast

PolychromatophilicErythroblast

OrthochromatophilicErythroblast

Reticulocyte

Erythrocyte

Basophilic erythroblast – ribosome synthesis.Polychromatophilic erythroblast – hemoglobin accumulation Orthochromatophilic erythroblast – ejection of the nucleus Reticulocytes become mature erythrocytes in 5 - 7 days.Reticulocytes: 0.5 to 1.5 % of RBCs.

Nutritional requirements for RBC production• Erythropoiesis also depends on adequate supplies of

the amino acids, iron, amino acids, iron, vitamins vitamins BB1212((cyanocobalamincyanocobalamin) and ) and folic acidfolic acid

• Reduced B12 or folate levels adversely affect cell division and maturation– There is a reduction in the RBC count. – RBC are abnormally large (macrocytes) –macrocytic

anemia.• Inadequate iron supply causes that hemoglobin

synthesis is restricted.– RBCs contain less hemoglobin than normal (hypochromic)

and are smaller than normal (microcytic).

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Pernicious Anemia

Blood smear from a person with pernicious anemia. Note the neutrophil hypersegmentation

Patient with severe iron deficiency anemia. In addition, there is marked anisocytosis and poikilocytosis as well as microcytosis

Microcytosis

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Erythrocytes - characteristics• Filled with hemoglobin (Hb)• Biconcave disk shape (thin center and thicker

edges) – large cellular surface area.• Flexible plasma membrane deforms easily –

passage through small diameter capillaries.– Membrane contains spectrin and other proteins that

allow them to change shape as necessary

• Absence of nucleus and cytoplasmic organelle – limits life span to about 120 days– more space for hemoglobin– reduced oxygen consumption

Destruction of Erythrocytes

• The life span of an erythrocytes is 100-120 days

• Old erythrocytes are engulfed by macrophages (spleen)

• Hemoglobin is split into globin and heme

• Heme is split into bilirubinand iron– Iron and globulin are recycled– Bilirubin is sent to the liver and

secreted in bile

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Hemoglobin

• Hemoglobin is the oxygen-carrying protein• Hb increases blood oxygen carrying capacity 100x.• Oxygen in the blood

– Dissolved in plasma 2 %– Combined with Hb 98 %

Hemoglobin Reactions

• Oxygenation: Hb + 4O2 →→→→ Hb(O2)4oxyhemoglobin The iron stays in the ferrous stateOne Hb can bind four O2 molecules

• Oxydation: Hb(Fe2+) →→→→ Hb(Fe3+)methemoglobin

• CO reaction: Hb + CO →→→→ HbCOcarboxyhemoglobin

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Hemoglobin

• Hemoglobin in adults– Hb A1 �2 �2

95% - 98%– Hb A2 �2 �2

1.5% - 3.5%– Hb F �2 �2

0.5% - 1%

Fetal hemoglobin has a greater affinity for oxygen than adult hemoglobin

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Oxygen Binding by Hemoglobin

OxyhemoglobinRelaxed binding structure has high O2 affinity,

is most stable in lungs

DeoxyhemoglobinTight binding structure has low O2 affinity,

is most stable in the tissue

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Oxygen-Hemoglobin Dissociation Curve• Sigmoid shape

– Binding of one molecule facilitate the second molecule binding

– P 50 (pO2 when Hb saturation is 50% ) 26.6 mmHg

• Normally pO2 in the arterial blood – 95 mmHg; Hbsaturation is 97%.

• In tissues pO2 – 40 mmHg;Hb is 75% saturated with O2.

• Therefore 25% of the O2 is delivered to the tissues

Oxygen transport in the blood• Quantity of O2 that will combine with the Hb

is 1.34 ml of O2 per 1g Hb • Normal person 15g/100ml of blood then

20 ml of O2 per 100 ml of blood• Arterial blood → O2 saturation = 97%

19,4 ml of O2 per 100 ml of blood• Venous blood → O2 saturation = 75%

14,4 ml of O2 per 100 ml of blood• Each 100 ml of blood transports 5 ml of O2

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Shifting the Oxygen - HbDissociation Curve

The Bohr effect: release of O2 by HbO2 into tissue is enhanced when pH is ↓and pCO2 is ↑ (right shift of HbO2 curve).

2,3-Diphosphoglyceric Acid (DPG) Alters O2 Affinity

• 2,3 DPG is a byproduct of anaerobic glycolysis.• DPG binding more strongly to T state, helps to

release O2. • The affinity of Hb for O2 diminishes as the

concentration of 2,3-DPG ↑ in the RBCs• Increase in levels of DPG helps adaptation to high

altitude.• In individuals who have become acclimatized to

living at high altitudes, the level of 2,3-DPG in the blood ↑, allowing the delivery of ↑ O2 to tissues under low O2 tension.

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CO2 Transport

• CO2 transported in the blood: – HCO3

- 89%– Dissolved CO2 in plasma 5%– Carbamino compounds 20%

Carbamino compounds – combination with Hb and plasma proteins

Hb

HCO3-

H+

COCO22

HH22OO

HH22COCO33

Carbonic Anhydrase

ClCl--

tissue Lumen of capillary vessel

OO22

KK++

Exchange

Bicarbonate-chloride shift maintains

electrical neutrality

CO2 + HbCarbamino-Hb

Gas Exchange in Tissue

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Alveolar air

HCO3-

lungLumen of capillary vessels

OO22

HbH+

Exchange

ClCl--Carbonic

AnhydraseKK++

HH22COCO33

HH22OOCOCO22

Gas Exchange in the Lung

CO2 Transport – Summary• CO2 production in peripheral tissues leads to

increased CO2 content in mixed venous blood• Major portion of CO2 produced in periphery is

transported as HCO3-

• It depend on erythrocyte carbonic anyhydrase• Some CO2 binds to Hb and form carbamino-

compound• Haldane effect: Hb that has released O2 binds

more readily to CO2 than Hb that has O2 bound to it

• Little CO2 is carried as dissolved CO2

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Complete Blood Count • Complete blood count (CBC) is a simple

blood test, this is a count of cells found in the blood.

• The test can diagnose and monitor many different diseases, such as anemia, infection, inflammatory diseases, and malignancy.

Complete Blood Count• The number of WBCs:

4,000 – 10,000 WBC/µµµµL• An increased number of WBCs

– Infections– Tumors (leukemia).

• A decreased number of WBCs– The bone marrow failing to produce WBCs– Increased removal of WBCs from the

circulation

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Complete Blood Count

• The number of platelets:150,000 and 400,000 platelets/µL

• If platelets count ↓– risk of uncontrolled bleeding

• If platelets count ↑– risk of uncontrolled blood clotting.

Laboratory Analysis of Red Blood Cells

• Number of RBCs – Men: 4,300,000 – 5,900,000 RBCs/µl– Women: 3,500,000 – 5,000,000 RBCs/µl

• Hb content in the blood– Men: 14 - 17 g/dl– Women:12 -15 g/dl

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Hematocrit (Hct)

• Low hematocrit– drop in RBC production by the bone marrow.

• High hematocrit– increase in the fraction of RBCs (polycythemia)– a drop in the plasma (e.g., fluid loss in burn

victims).

Description of RBCs

• Description by size – mean corpuscular volume (MCV): 81 - 100 fl

• microcytic: smaller in size (< 81 fl)• macrocytic: larger in size (> 100 fl)• normocytic: normal size (81 – 100 fl)

• Description by color– mean corpuscular hemoglobin (MCH): 27- 34 pg

• normochromic (normal Hb content)• hypochromic (low Hb content)• hyper chromic (high Hb content)

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RBC disorders – anemias• Anemia is decreased RBCs affecting tissue

oxygenation

• Practical - Low Hb or Low Hematocrit• Majority of clinical signs of anemia related to low

tissue oxygen levels– Fatigue; skin pallor– Weakness; faintness; headache– Compensation results in increased heart and respiratory

rates

Mechanism of Anemia

• Decreased Production:– Nutrient Deficiency.

• Iron, B12/Folic acid

– Hemopoietic cell damage:• Aplastic, Hypoplastic – Neoplasms, radiation, drugs

• Increased loss / destruction:– Blood loss anemias - parasites, bleeding– Hemolytic anemia – Autoimmune, mechanical,

drugs, parasites.

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Sickle Cell Disease• Sickle cell disease –

defective Hb• Sickle cell Hb molecules

are stiff and form into the shape of a sickle.

• They tend to cluster together, and cause a blockage of the vessels

• Sickle cells die after about 10 to 20 days.

• Cause is generally cancerous transformation of the red bone marrow

• Abnormal increase in blood cells. – RBC count – 8 – 10 x106/ µl. – Hematocrit – as high as 70 to 80%.

• Symptoms:– Increased blood viscosity or thickness– Slow blood flow and coagulation problems– Frequent hemorrhages

• Treatment may include:– Blood removal– Irradiation and chemotherapy

Polycythemia (overproduction of RBCs)

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Polycythemia• Relative polycythemia

– rise of the erythrocyte level in the blood because of reduced blood plasma. Relativepolycythemia is often caused by fluid loss.

• Secondary polycythemia– occurs in individuals living at high altitudes

(4275 to 5200 meters), where oxygen availability is less than at sea level. This type of secondary polycythemia is called physiologic polycythemia.