Components of the blood

The blood in general is composed of plasma and cells, the plasma itself is composed mainly of water and we can find a lot of elements in the plasma like hormones, enzymes, plasma proteins, electrolytes or gases. All these things are dissolved or carried in the blood either by being dissolved or carried by the plasma protein and we can find the cells like erythrocytes, leucocytes and platelets. So blood is composed mainly of plasma and formed elements, which we are going to study. We are going to concentrate on the physical characteristic of the blood, its functions and the viscosity of both the blood and lymph. So as seen in slide 2; this is a sample of blood, which is venous, if it is spun in a centrifuge, the heavier formed elements are packed down by centrifugal force and the less dense plasma remains at the top, so if we take a sample of venous blood and if we centrifuge it the dense/heavy elements of the blood (cells) will stay at the bottom and plasma will go upwards.

Plasma
The plasma has 2 components: 1) cellular components (formed elements) which includes erythrocytes 2) the Buffy coat which is a whitish layer present at the site of the erythrocyte plasma and it contains Leukocytes and platelets. We also have liquid components (plasma) which makes about 55% of the blood making the cells about 45% of the blood. Erythrocytes normally constitute 45% of the total volume of blood. This percentage is known as the hematocrit SO THE CELLS IN THIS PERCENTAGE ARE KNOWN AS THE HEMATOCRIT-. In males and females, this percentage might differ:
IMPORTANT:

(in males: 45- 47% 5%

in females: 40-45% 5% )

Plasma is the fluid portion of the blood which contains proteins which are the most important component of blood (albumins, globulins, and fibrinogens) these are the plasma proteins and we can also find in the plasma nutrients, metabolic end products, hormones, and mineral electrolytes.

Plasma is obtained when unclotted blood is centrifuged. The fluid which rises above
the cellular elements is in fact the PLASMA.

Serum is plasma from which fibrinogen and other coagulation proteins have been removed as a result of clotting. It contains high level of serotonin
(released from platelets during clotting). It is obtained when clotted blood is

centrifuged. The fluid above clotted blood is SERUM i.e. Serum is the liquid part of the blood after the coagulation.

. These are cellular elements in cell; they include platelets, Erythrocytes, different types of leukocytes and the subtypes of leukocytes -1- granule -2- Agranule cytes. The total plasma protein is 7-8 g/dl Albumin about Globulin about Fibrinogen about 4.5 g/dl 2.5 g/dl (alpha, beta and gamma globulins) 0.3 g/dl

{Its important to know the amount of each protein}. Most plasma proteins are produced by the liver, except for hormones and gamma globulins (they are formed by plasma cells). Being 8% by weight of plasma volume, plasma proteins serve a variety of functions, but they are not taken up by cells to be used as fuels or metabolic nutrients as are most other plasma solutes, such as Glucose, fatty acids, and amino acids.

Hypoproteinemia
Hypoproteinemia is seen in: a. liver disease(low production of protein- less formation-) b. kidney diseases(loss of protein) such as Nephritic syndrome you find signs which are protein urea-means protein uric-

In the liver hypoproteinemia; decreases the concentration of protein in blood.

Albumin:

MW= 69000

It Accounts for about 60% of plasma protein It acts as a carrier of many substances in the circulation, It is an important blood buffer and the major blood protein contributing to the ONCOTIC PRESSURE (plasma osmotic pressure). This pressure helps to keep water in the bloodstream

Globulins ( and ) act as enzymes and carriers.

- They are produced by the liver. - Antibodies (gamma globulins, immunoglobulin) produced by plasma cells. - Fibrinogen produced by liver forms fibrin threads of blood clot. In the plasma we have: nutrients and hormones and the difference between hormones and enzyme is that:

{hormones are secreted from specific organs and effects in the body directly, for
example: antidiuretic hormone (ADH) secreted from the hypothalamus it acts on the connecting tubules in the kidney}.

{enzymes are secreted from one organ and acts locally in that organ, for example : pepsin it is secreted from the stomach it acts locally in the stomach }.
Electrolytes; Ca++, K+, Cl-, HCO3-, Na+ ions help to maintain the osmotic pressure. Sodium ions are the major solute contributing to blood osmotic pressure and they help in maintaining a normal blood pH. (Normal pH is 7.35 or 7.45) it is a trump. Above 7.45 we call it alkalosis Below 7.35 we call it acidosis - its danger leads to death that's why it is extremely important for patients to get intensive per units of ABG (arterial blood gases) and they should be taking it hourly in order to check if theyre blood is in the state of acidosis or alkalosis.

We have 2 types of acidosis and alkalosis 1) We have metabolic acidosis or alkalosis 2) respiratory acidosis or alkalosis (the function of the respiratory system is in the acid base balance, it is the moment to moment control of acid base balance determined by CO2 or O2). ***when we study the GI we can ask about metabolic acidosis or alkalosis but once we study the respiratory system we have to know by heart the respiratory acidosis and alkalosis.*** The formula that makes a difference between acidosis and alkalosis is that when the is shift in the hemoglobin-oxygen dissociation is curved to the right It increases CO2 It increases the H ions which is the product of metabolism It increases the temperature. It increases 2,3 bisphosphoglycerate, all these factors shift the curve to the right.

Physical Characteristics and Volume:

Total blood volume: 8% of body weight, slightly alkaline pH between 7.35 and 7.45. -Blood is denser than water and about 3-4 times more viscous. Why? Because of the cells (cell components).

Blood functions:
There are six functions:
1) Transportation O2 lungs cells CO2 cells lungs

Nutrients GI cells waste from cells kidneys -Blood provides O2 and nutrients to the cells and removes CO2 and other waste products from them. 2) Defense: WBCs * blood proteins antibodies (Igg, Igm,. )* 3) Temperature regulation - absorbs and distributes heat throughout body and skin 4) Prevents loss of blood blood clots 5) Hormone movement endocrine gland cells 6) Regulates pH through buffers

Formed Elements: we have electrocytes, and these show all the components of
blood

Viscosity INCREASE when hematocrit value or number of RBCs rises.

The most important element in the blood, which is responsible for blood viscosity

-The formed elements are present in the buffy coat and the bottom red layer (RBCs, WBCs and platelets). -Erythrocytes have no nuclei or organelles and the platelets are cell fragments. Only the leukocytes are true cells. -Erythrocytes and platelets do not divide.

Blood viscosity: It is Plasma protein, the main component of blood elements and is what sets the principle of the blood viscosity. Viscosity is increased when hematocrit value or Number of RBCs rise.

Erythrocytes
Plasma membrane is in an enclosed sac full of hemoglobin (thats why they are called Bags of hemoglobin) with no nucleus or organelles. *whats the importance of RBCs ??? It contains hemoglobin which is responsible for the transfer of oxygen (mainly), and at a lesser rate carbon dioxide and hydrogen ions.

*Structural characteristics: 1) Small, biconcave shape which provides a large surface area for diffusion of oxygen molecules across the membrane. 2) Concentration; in females 4.7-5 million per cubic mm, in Males 5.2-5.5 million per cubic mm 3) Lacks nucleus; life span = 120 days 4) Thickness; 2.5/1 so oxygen can diffuse rapidly between exterior and innermost regions of the cell 5) Relay on glycolysis for ATP production (not on oxidative phophorylation because it has no mitochondria)

*RBC Production: 1) During early weeks of pregnancy production of primitive nucleated RBCs in yolk sac (Wikipedia:- yolk sac: membrane sac attached to an embryo providing early nourishment in the form of a yolk) 2) During the middle trimester production of RBCs from the liver (mainly), spleen and lymph nodes (Wikipedia:- first trimester= months 1-3 of pregnancy, middle trimester= months 4-6, third trimester= months 7-9) 3) During the last month of pregnancy and after birth (0-5years) all from the bone marrow. 4) 5-10 years from the shaft of long bones (then it becomes fatty and its contribution in forming RBCs is reduced gradually and eventually stops completely after 20 years. The heads of long bones however, continue to form RBCs ) 5) >20 years almost all in membranous bones.

*Relative rates of RBC production in bone marrow of different bones at different ages.

Hemoglobin
*Parts: 1) Globin Protein four highly folded polypeptide chains 2) Four iron containing non protein groups (heme groups), each can combine reversibly with one oxygen molecule, thus each hemoglobin molecule binds with 4 oxygen molecules. - The relationship between hemoglobin and oxygen is reversible (hemoglobin binds oxygen and release it to tissues)

*Role: 1) Transfer oxygen molecule and carbon dioxide molecules 2) Buffer capacity

* Average values of hb:

Adult males 16 g/100ml Adult females 14 g/100ml

Erythropoiesis
*Erythropoiesis: RBCs Production (because RBCs cant divide, the old ruptured cells must be replaced by new cells produced in bone marrow). Although the various formed elements have different function, they all arise from the same stem cell.

1) In children, most bones are filled with red bone marrow that is capable of blood cell productions. Red bone marrow is the ultimate source for leukocytes and platelets as well. 2) As a person matures, however, fatty yellow bone marrow that is incapable of erythropoiesis gradually replaces red marrow, which remains only in a few isolated places, such as the sternum (breastbone), ribs, and upper ends of the long limb bones.

Committed stem cell that form RBC, Granulocytes, monocytes, platelets

* Pluripotent hematopoietic stem cell (PHSC):

-The 'mother of all cells'the progenitor of all hematopoietic cellse.g. platelets, RBCs, neutrophils, macrophages, lymphocytes. -Derived from mesenchyme once committed it follows its path.

*PHSC

gives: 1. Committed stem cells that produce RBC, granulocytes, monocytes , platelets 2. Committed stem cells that give lymphocytes 3. PHSC that keeps a supply of committed stem cells

*Notes: 1) growth inducers like interleukin-3 makes PHSC to give different committed stem cells. 2) Differentiation of different colonies into different blood cells is done by different inducers 3) Erythropoiesis begins when a stem cell is transformed into a proerythroblast (committed cell)

RBCs Maturation Stages

Time needed for committed stem cells to develop to mature erythrocytes is about 5-7 days.

1) Proerythroblast: is the first cell belonging to the red blood series. 2) Early Erythroblast: (ribosome synthesis) little of Hb starts to accumulate 3) Late Erythroblast: (hb accumulation) Hb concentration is increased until it forms almost 34% of volume of the cell. 4) Normoblast: (ejection of nucleus) 5) Reticulocyte: Very few Hb is formed. It is the last stage which does not contain nucleus and the cytoplasmic organelles are disappearing and the only remnants of these remained. They leave the bone marrow and stay in the blood for 1-2 days and finally they form mature RBC. Normal reticulocytes number in circulation is about 1% of total RBC number 6) Mature Erythrocyte

Erythropoiesis control
* low O2 levels do not stimulate erythropoiesis by acting directly on the red bone marrow. Instead, it reduces O2 delivery to the kidneys, stimulates them to secrete the hormone erythropoietin into the blood and this hormone in turn stimulates erythropoiesis by the bone marrow.

*Erythropoietin (EPO): A hormone produced mainly by tubular epithelial cells in the kidney (90%) and hepatocytes in liver (10%) that promotes the formation of red blood cells in the bone marrow. EPO is a glycoprotein (a protein with a sugar attached to it). Human EPO has a molecular weight of 34,000.

1) Stimulus: A drop in normal oxygen levels (hypoxia) triggers erythropoietin formation. Hypoxia is the most potent stimulus for erythropoietin production. Other factors that increase erythropoietin production are Androgen, alkalosis and Catacholamines. 2) When less O2 is delivered to the kidneys, they secrete the hormone erythropoietin into the blood. 3) Erythropoietin stimulates erythropoiesis (erythrocyte production) by the bone marrow 4) The additional circulating erythrocytes increase the O2-carrying capacity of the blood.

5) The increased O2-carrying capacity relieves the initial stimulus that triggered erythropoietin secretion.

Destruction of Erythrocytes
The anucleated condition of erythrocytes carries with it some important limitations. -Red blood cells are unable to synthesize new proteins, to grow, or to divide. -Erythrocytes become old as they lose their flexibility and become increasingly rigid and fragile, and their contained hemoglobin begins to degenerate. -Aged RBCs have: Metabolic activity Enzyme activity ATP Membrane Lipids
Fragile Membrane

Cells Rupture as they pass through narrow spaces in spleen

*Process: 1) In the red pulp of the spleen, RBC rupture when they try to squeeze through because of their fragile old membrane. For this reason, the spleen is sometimes called the red blood cell graveyard. 2) Macrophages in spleen, liver and red bone marrow phagocytize dying RBC.

-Globin breaks into amino acids, which can be reused to produce other proteins -Heme iron and porphyrin -Fe removed and recycled in spleen -Porphyrin converted to bilirubin (bile pigment) Yellow pigment secreted by liver into bile, which is excreted in urine and feces

Diseases of Red Blood Cell

Anemia :
*Definition; a decrease in the number of red blood cells (RBCs) (less than the normal quantity of hemoglobin in the blood). However, it can include decreased oxygenbinding ability of each hemoglobin molecule. *Causes: 1) Insufficient number of RBC 2) Low hemoglobin content 3) Abnormal hemoglobin *Effects:

Decreased viscosity anemia Decreased resistance to blood flow hypoxia Dilatation of blood vessels More cardiac output More blood returns to the heart

Polycythymia:
*Definition: a disease state in which the proportion of blood volume that is occupied by red blood cells increases.

*Types: 1) Primary Polycythemia: Due to increased activity of hemocytoblastic cell of bone marrow. 2) Secondary Polycythemia: Due to hypoxia.

*Effects:

Increased cardiac output

Blood volume Hematocrit viscosity decreased blood flow Decreased venous return to the heart Decreased cardiac output

Increased venous return

Polycythemia Leads to

Increased blood pressure

More O2 is extracted from Hb and thus deoxygenated blood is increased leading to bluish discoloration of the skin (cyanosis)

We are sorry for any mistake in this lecture ,,, We want to thank ANMAR HADAD , and we wish to you all the success in medicine <3 <3

Done by

Reem Qawasmi Mais Khader