Physiology of RBC BDS 2014

7/25/2019 Physiology of RBC BDS 2014

1/44

Physiology of the RBCs

Presented by A/P Dr. Magdi El Sersi

2


2/44

2

At the end of the lecture student should be able to:

1. Describe the morphological features of RBCs, their normal counts and their

function

2. Describe the structure of HB molecule, its function and normal concentration

3. Describe the life cycle of RBCs

4. Describe the production of new RBCs

5. Describe the fate of RBCs6. Define anemia and outline the different classifications of anemia

7. List the different blood indices

8. Describe the physiological effect of anemia

9. Define polycythemia and outline its classification

References

1. Textbook of Medical Physiology 12th edition By Guyton and Hall 2011

2. Ganong's Review of Medical Physiology .


3/44

Formed elements comprise 45% of blood and are:

Erythrocytes, leukocytes, and plateletsOnly WBCs are complete cells

RBCs have no nuclei or organelles, and platelets are just cell fragments

Most formed elements survive in the bloodstream for only a few days

Most blood cells do not divide but are renewed by cells in bone marrow

3


4/44

Non nucleated Biconcave discsMean diameter ~7.8

Thickness of 2.5 at the thickest point and 1 or

less in the center.

The average volume of the red blood cell is 90 to

95 3.

It has no mitochondria, or other organelles.

Filled with hemoglobin (Hb), a protein that functions

in gas transport

ERYTHROCYTES (RBCS)


5/44

Importance of biconcave shape

Allows for flexibility and shape change while squeezingthrough capillaries.

Increases the surface area for diffusion of gases whiledecreasing the distance through which gases have todiffuse.

Variations in the shape and dimensions of the red cellare useful in the differential diagnosis of anemias


6/44

Cell Membrane

The membrane skeleton is made up of spectrin and is anchored tothe transmembrane protein band 3 by the protein ankyrin

Band 3 is also an important anion exchanger


7/44

Red Cell FragilityIn solutions with a lower osmotic pressure RBC swell, becoming spherical

and eventually lose their hemoglobin (hemolysis).

The hemoglobin of hemolyzed red cells dissolves in the plasma, coloring

it red.

When osmotic fragility is normal, red cells begin to hemolyze when

suspended in 0.5% saline

In hereditary spherocytosis the cells are spherocytic in normal plasma

and hemolyze more readily than normal cells in hypotonic NaCl solution.

Hereditary spherocytosis is one of the most common causes of hereditary

hemolytic anemia.

The spherocytosis is caused by abnormalities of the protein network that

maintains the shape and flexibility of the red cell membrane.


8/44

Number of Red Blood Cells in the Blood

Men: 5,200,000 (300,000) cells / mm3.

Women: 4,700,000 (300,000) cells / mm3.This difference is mainly due to difference in hormonal

profile between the 2 sexes (male sex hormones,

androgens, stimulate hemopoiesis)

The number of circulating RBCs remains

constant and reflects a balance between RBC

production and destruction

Too few RBCs leads to tissue hypoxia

Too many RBCs causes undesirable blood viscosity


9/44

Erythrocyte Function

1. The major function of RBCs is to transport hemoglobin, which in turn

carries respiratory gases.2. They contain a large quantity of carbonic anhydrase, an enzyme that

catalyzes the reversible reaction between CO2 and water to form

carbonic acid (H2CO3).

3. The hemoglobin in the RBCs is an excellent acid-base buffer and

responsible for most of the acid-base buffering power of whole blood.


10/44

Structural characteristic of RBC which make them a

good gas transporter :

1. Its small size and biconcave shape provide a huge surface arearelative to volume

2. over 97% hemoglobin.

3. Erythrocytes lack mitochondria and generate ATP by anaerobic

mechanisms, so do not consume any of the oxygen.


11/44

Hemoglobin molecule Hemoglobin is composed of the protein globin each of which is

bound to a heme group

Globin is made up of 2 and chains, Each heme group bears an atom of iron,

Each iron can bind to one O2molecule

So each hemoglobin molecule can transport 4 molecules of O2

If you know that there are 250 million molecules of Hb / cell you can imagine how

much oxygen is carried by each RBC


12/44

Function of Haemoglobin


13/44

Hemoglobin combines reversibly with oxygen

This is facilitative reaction

Each gram of hemoglobin combines with about 1.39 ml O2 / g Hb underoptimal conditions

But under normal conditions some hemoglobin exists in forms such as

Methemoglobin (metHb) an oxidized form of hemoglobin that hasan increased affinity for oxygen, resulting in a reduced ability torelease oxygen to tissues

Carboxyhemoglobin (COHb) Combined with CO

The oxygen carrying capacity of hemoglobin when fully saturated withoxygen binds with 1.34 ml O2/ g Hb.

13


14/44

14

Maximal capacity of Hb to bind O2 is also known as the Oxygen carry ing c apaci ty of

Hb. The most important factor determining Hb-oxygen saturation is the PO2 of

blood

Each molecule of hemoglobin can bind 4 molecules of oxygen to

give HbO2 (Oxyhemoglobin or oxygenated hemoglobin).

Hb4 + 4O2 Hb4O8


15/44

15

Oxygen is transported in two forms

Bound to hemoglobin 98.5%

Dissolved in plasma 1.5%

Oxygen is relatively insoluble in water, only3 ml can be dissolved in 1 L of blood at the

normal arterial PO2 of 100 mmHg.

The other 197 ml of oxygen in a liter of

arterial blood, is transported in theerythrocytes reversibly combined with

hemoglobin.


16/44

The amount of oxygen physically dissolved in the blood depends on its solubility

and is proportional to partial pressure (Henrys law)

Gas content = solubility * partial pressure

At 37oC the solubility of O2 in blood is 0.03 ml/L for every mm Hg increase in

partial pressure.

16


17/44

17


18/44

18

CO2 is transported in 3 forms:

Physically dissolved (7%)

In combination with hemoglobin

(23 %, in the form of carbamino

hemoglobin).

As bicarbonate (70%)


19/44

19

The first reaction is rate-limiting and is very slow unless catalyzed by the

enzyme carbonic anhydrase

Carbonic acid dissociates rapidly into a bicarbonate ion and a hydrogen ion

Once formed, most of the bicarbonate moves out of the erythrocytes into the

plasma via a transporter that exchanges one bicarbonate for one chloride ion

(chloride shift or Hamburger phenomenon).


20/44

20


21/44

Quantity of Hemoglobin in the Red Cells

In normal people, the percentage of hemoglobin is almostalways near the maximum in each cell.

When Hb formation is deficient, the % of Hb in the cells may

fall and the volume of the RBC also decrease because ofdiminished hemoglobin to fill the cell.

Men : average of 15 gm/100 ml.

Women: average of 14 gm/100ml.


22/44

Erythropoiesis

Production of Red Blood Cells

Erythropoiesis

During this reticulocyte stage, the cells pass from the bone marrow into the blood

capillaries by diapedesis

within 1 to 2 days the cell become a mature erythrocyte.

Because of the short life of the reticulocytes, their concentration is normally slightlyless than1%


23/44

I. Hormonal control

1. Erythropoietin Glycoprotein (65 amino acids) 90% from kidneys 10% live

Stimulated mainly by Hypoxia Anaemia Hemorrhage High altitude Lung disease

Heart failure

Norepinephrine and epinephrine andseveral of the prostaglandins stimulateerythropoietin production.

also stimulates the release of reticulocytesto the circulation.

CONTROL OF ERYTHROPOEISIS


24/44

Hormonal Controlcont

2. Other hormones

Androgens, Thyroid, cortisol & growth hormones are essentialfor normal red cell formation

Androgens e.g. testosterone: increase erythropoiesis through

directly stimulating bone marrow and indirect stimulation oferythropoietin release .

Thyroid hormones (T3 and T4): stimulate the metabolism

of all body cells including the bone marrow

Glucocorticoids: stimulates the general metabolism of all

cells including the bone marrow.


25/44

II. Nutritional requirements for RBC formation

1. Amino acidFor synthesis of Hemoglobin

2. Iron

Essential for the synthesis of Hemoglobin. Deficiency causes Microcytic, Hypochromic Anemia.

3. B12 (Cyanocobalamine) & Folic Acid: Deficiency causes Megaloblastic Anemia Or Pernicious

4. Other elements: Vit C -Iron absorption, Copper, Cobalt, zinc, manganese


26/44

Maturation of RBCs Requires

Vitamin B12 and Folic Acid

Both of vitamin B12 and folic

acid are essential for the

synthesis of DNA

Intrinsic factor (a glycoprotein

secreted by the parietal cells of

the gastric glands) combines

with vitamin B12 in food and

makes the B12 available forabsorption by the gut.


27/44

lack of either vitamin B12 or folic acidcauses abnormal and diminished

DNA and, consequently, failure of

nuclear maturation and cell division.

The erythroblastic cells of the bonemarrow:

Fail to proliferate rapidly.

Produce mainly macrocytes.

The cell has a flimsy membrane and

is often irregular, large, and oval

instead of the usual biconcave disc.

Effect of Deficiency of Vitamin B12 and Folic Acid


28/44

Life span in blood stream is 60-120 days

Old RBCs are phagocytosed and/or lysed mainly extravascular in thereticulo-endothelial system (Liver, Spleen and Bone marrow).

FATE OF RED BLOOD CELLS


29/44

ROLE OF THE SPLEEN

The spleen is an important blood filter that removes agedor abnormal red cells

It also produces RBCs when required as well as

lymphocytes, plasma cells and antibodies (site for

extramedullary haemopoiesis)


30/44

Erythrocyte Disorders

Anemia deficiency of hemoglobin in the blood( low

oxygen-carrying capacity)

This can be caused by

i. Decrease number of RBCs

ii. Decrease hemoglobin in the cells

Anemia is a symptom rather than a disease

Blood oxygen levels cannot support normal metabolism

Signs/symptoms include fatigue, paleness, shortness ofbreath, and chills


31/44

31

Red blood cells indices:

7 values related to RBCs are reported in the CBC including

1. Hemaoglobin (directly measured )

2. Red blood cell count (directly measured )

3. Haematocrit (Hct) (directly measured )

4. Mean corpuscular volume (MCV)

5. Mean corpuscular haemoglobin (MCH).

6. Mean corpuscular Haemoglobin.concentration (MCHC).

7. Red blood cell distribution width(RDW).

Laboratory evaluation of anemia:


32/44


33/44

Hematocrit (PCV)

It is the percentage ratio of RBCs volume

to the total blood volume.

number of RBC

ECF ; Dehydration


34/44

Lmillions/incountRBCs

10XPCV

Mean Corpuscular Volume (MCV)

This is the average volume of one red cell.

MCV =

The average value is 90 fL ( 3).

The normal range is 75 to 100 fL (normocytes).

RBCs with MCV above 100 fL are macrocytes,and those with MCV less than 75fL are microcytes.


35/44

The average value is 30pg.

The normal range is 26 to 34 pg(normochrom ic cells).Below 26 pg. the cells are hypochromic

Above 34 pg. the cells are hyperchromic.

Mean Corpuscular Hemoglobin (MCH):This is the average amount of Hb in one RBC in picograms

(pg).

MCH =Lmillions/incountRBCs

10X(mg/dL)contentHb

Mean corpuscular Hb concentration (MCHC):


36/44

The average value is 34 %.

The normal range is 33-35 g/100 mL RBCs

Red blood cell distribution width (RDW):

The coefficient of variation of RBC volume (indicates the

degree of anisopoikilocytosis)

Normal RDW value is 10-14%

Mean corpuscular Hb concentration (MCHC):This is the average amount of Hb per 100 mL of RBCs.

MCHC =100

PCV

(mg/dL)contentHbX

M h l i l l ifi ti f i


37/44

Morphological classification of anemia

1. Normocytic normochromic anemia: Normal MCV (size of RBCs) and normal MCH andMCHC (amount of Hb in each RBC), but total RBCscount is decreased.

Causes of normocytic normochromic anemia:

Acute blood loss (hemorrhage).

Bone marrow depression by drugs, x-ray or

malignant disease (Aplastic anemia).

Excessive hemolysis (destruction) of RBCs

2 Mi i h h i i


38/44

2- Microcytic hypochromic anemia:

It is a type of anemia with small size of RBCs (MCV


39/44

Etiological classification of Anemia:

I- Anemia Due To decreased Hemoglobin Content

Iron-deficiency anemia results from:

A secondary result of hemorrhagic anemia

Inadequate intake of iron-containing foods

Impaired iron absorption

Pernicious anemia results from:

Deficiency of vitamin B12 Lack of intrinsic factor needed for

absorption of B12


40/44

II- Insufficient Erythrocytes

Hemorrhagic anemia result of acute or chronic loss of

blood

Hemolytic anemia prematurely ruptured erythrocytes

Aplastic anemia destruction or inhibition of red bonemarrow.

III Ab l H l bi


41/44

III- Abnormal Hemoglobin

Thalassemias absent or faulty globin chain in hemoglobin

Erythrocytes are thin, delicate, and deficient in hemoglobin

Sickle-cell anemia results from a defective gene coding foran abnormal hemoglobin called hemoglobin S (HbS)

HbS has a single amino acid substitution in the beta chain This defect causes RBCs to become sickle-shaped in low

oxygen situations


42/44

Effect of anemia

The effects of anemia aremostly on the circulatory

system:

It increases the work load

on the heart.

It is accompanied by

hyperdynamic circulation

and functional murmurs. It leads to tissue hypoxia

and acute heart failure

P l th i


43/44

Polycythemia

Polycythemia is an abnormal excess of erythrocytesIt increases blood viscosity, causing it to sludge, or flow

sluggishly.

It is classified to:

A. Primary polycythemiai. Acquired ; Polycythemia vera

ii. Hereditary

B. Secondary polycythemia

High altitude , Smoking , Hypoxemia, Chronic lung

disease ,Sleep apnea.


44/44

Documents

Physiology of RBC BDS 2014