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الرحيم" " الرحمن الله بسم

Body fluids & the blood

Note: this lecture will be divided into two parts, the first will be a complement to the previous lecture which was about the body fluids, while the other part will be about blood components.

In the previous lecture we discussed the body fluids and how the body should keep the volume of them constant, and that can be achieved by :

1- Hydrostatic pressure (it is the pressure that pushes the plasma-the liquid part of the blood- out of the capillary, and it has a value in the Arterial end that differs from the Venus end ).

2- Osmotic pressure.

In the arterial end of the capillary the net filtration pressure is 13 mmHg that pushes the plasma out of it, however in the Venus end the net filtration pressure is -7 mmHg whish cause the re-absorption of water there.

So the plasma leaves the capillary from the arterial end carrying the nutrients ,vitamins ,and other important substances to the tissues, then it washes out the interstitium from metabolic waste(toxic materials,co2...etc) and finally the plasma goes back to the capillary from the Venus end but in different amount. (the amount of plasma leaves the capillary not exactly equal to that which will return to it) so here the lymphatic system which is goes around the capillaries play a crucial role in: 1- Gathering the extra amount of plasma that remains in the

interstitiumin and get them back to the capillaries.2- Washing out the plasma protein particles which have left the

capillaries and then get them back to the vascular system.

So, by that the body maintains the volume of its fluids constant.

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Now, how the body keeps the osmolarity of the fluids constant???

The normal osmolarity of the internal body fluids is isotonic (normotonic) which equals to 280-300 milli-osmoles/liters.

*The osmolarity can be calculated by the equation:

The osmolarity = the molarity *dissociation factor

As we know there are 3 types of solutions:

1-hypertonic solution (increased number of particles, decreased amount of water)

2-hypotonic solution (decreased number of particles, increased amount of water)

3-isotonic solution (e.g: normal saline, glucose dextrose which is used in the hospital)

* the osmolarity of the isotonic solutions is (280-300 milli-osmoles/liters)

90% of the osmolarity in the plasma or in the Extracellular body fluids related to the NaCl concentration, while the osmolarity inside the cell is mainly related to the Ka concentration, and because the extracellular fluids concern us more , the NaCl particles are the major issue .

When we are talking about osmotic equilibrium in the body fluids you have to remember these 2 important principles:

1 -Osmolarity of ECF and ICF must remain almost equal :that doesn't mean it has to be normotonic all the time, it means that if there is a change in the ECF toward hypertonic, for example,the ICF should follow that change and become hypertonic too, cause you can't see that the extracellular is normotonic and the intracellular is hypertonic/hypotonic or vice versa; that’s because the barrier

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between the extracellular and the intracellular compartments is the cytoplasmic membrane which is in turn highly permeable to water molecules, so any change of water concentration in either sides of the cell it will be followed by water movement either in or out until it reaches the equilibrium.

2-The cytoplasmic membrane neither permeable to Na nor Ka however it's highly permeable to water molecules ,so

that’s explain why there is about 150 milli-molar Ka particles inside the cell and outside it just about 5 milli-molar ,and why there is 140 milli-molar Na outside the cell and only 8 milli-molar inside it, and this situation should remain like

that all the time .So the cytoplasmic membrane is impermeable to the particles which are responsible for the

osmolarity (NaCl),however there are other particles that can go throw it without affecting the osmolarity.

***Keep in mind that whenever you heard osmolarity or body fluid concept you should immediately remember NaCl

particles

Example:A 70 Kg patient is dehydrated (losing of water),when measuring the NaCl molarity we calculated the osmolarity of blood plasma molecules which is equal to 320 mOsm/liter.

--How much water is needed to restore plasma osmolarity to 280 mOsm/L??.

The osmolarity was found to be 320 mOsm/liter which is higher than the normal osmolarity (300 milli-osmole), so we have a hypertonic solution which is abnormal, that's because the patient has lost high amount of water, and that causes the reduction of water particles while the number of solutes particles increased, so in order to get the normal osmolarity back we have to dilute the NaCl particles by increasing water concentration until we get the tonicity equal to 300 0r 280.

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In order to calculate how much water we need to achieve that, we should do several steps:

First: assume that;

The ECF is 20% of body weight (normal) =20%*70=14 liter

The ICF is 40% of body weight = 40%*70=28 liters

The summation of these which is the volume of the body fluid in the patient: 14+28=42 liters

Number of osmoles = the volume*osmolarity

Number of osmoles =42*320(from the question)= 13440 milli- osmoles

In the whole body of the patient

The number of osmoles in the extracellular = the volume of the extracellular fluid*osmolarity

The number of osmoles in the intracellular = the volume of the intracellular fluid*osmolarity

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Second: we have to know the volume of water that we should add in order to return the normal osmolarity back.

The volume of water = number of osmoles/osmolarity

In order to calculate the volume of water that we should give to the patient, we first have to find the total volume of water that should be present in his body after treating him to get the normal osmolarity back, which can be achieved by dividing the number of osmoles from the

previous step by the normal osmolarity :

13440 milli-osmoles/280(milli-osmoles/liter) =48 liters

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The patient has 42 liters before treatment, with a hypertonic extracellular compartment, so in order to get back to the normotonic there should be 48 liters inside his body.

The difference = 48-42 = 6 liters In the result I need to give that patient 6 extra litres in order to dilute the particles in his body and get back to the normotonic solution, which is the answer of our question.

Question: you have a normal person with a normotonic solution, if he drinks 3 liters of pure water ,what will

happen ??the water will go throw the GI track the vascular system in the plasma capillaries interstitial compartment ,so after drinking 3 litres of water the extracellular fluid will be hypotonic, meanwhile the intracellular fluid will still isotonic.

This is not acceptable because the osmolarity should be equal in and outside the cell ,and homeostasis will not accept this situation, so the water will start to move from the outside to the inside where the cytoplasmic membrane is highly permeable to water molecules and accepts that movement until it reaches the equilibrium ,and that's will happen when the osmolarity is equal in and out which is-

in this case - hypotonic in both sides, WHY??

) Because some of the extra water will go from the outside to the inside, and when it reaches the equilibrium there will be more water inside and more water outside

compared to the normotonic situation which is hypotonic.(

In summery when you drink high amount of pure water you will have hypotonic intracellularly and hypotonic extracellularly.

If another person drinks a hypertonic solution, after a while extracellular fluid (interstitial and plasma) will be hypertonic which is not acceptable,( inside the cell normotonic ,outside the cell hypertonic), so the water moves in the opposite direction from inside the cell to the outside until it reaches the equilibrium.

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When the intracellular fluid loses water it will transfer from normotonic to hypertonic, the extracellular will still hypertonic although it got some extra water, so by the end of the equilibrium inside and outside the cell will be hypertonic.

If a third person doesn’t drink hypertonic or hypotonic solutions, instead he drinks normal saline (a

normotonic solution)?? There will be no change in the osmolarity of both

intracellular and extracellular, because he drank a normotonic solution, so if you add 3 liter,7 liter,100 liters of normotonic solution to a normotonic solution it won't change the osmolarity, instead the volume of the plasma will increase because the starling capillary circulation will not allow the plasma to remain in the interstitial compartment.

The Edema:

We mentioned that under normal condition the body should have 42 litres of fluid that always should be constant (no decrease no increase),and that we have what is called hydrostatic pressure that pushes the plasma out of the capillaries which equals to 30 mmHg ,but, if we have a situation where the hydrostatic pressure instead of 30 it is 40 mmHg or 45 mmHg,that indicates that the amount of plasma which will leave from the capillary will be increased(the plasma filtration increase) which will cause a pathological phenomenon called ( Edema ).

***The edema: [is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body] (Wikipedia)

The edema has two major groups:

1- Intracellular edema : (very rare)Depression in the metabolism inside the cell - mainly when we have defect in Na/Ka pump- will lead to cell swelling which is the intracellular edema.

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*Na/Ka pump is very crucial to our life, and the inhibition of that pump will lead to cell death.

There is a special type of fish which found to be toxic to the human being and causes death, that 's because this type of fish contains an inhibitor to the Na/Ka pump, which will block the Na/Ka pump, the respiration will stop ,the action potential will stop and everything will stop, so the human being dies.

2- The extracellular edema: (the major edema in medicine) It is the accumulation of plasma in the interstitial compartment or in the vascular system.

The major cause of extracellular edema is an increase in the capillary pressures (hydrostatic pressure, osmotic pressure) which will cause extra filtration of plasma that results from many diseases and abnormalities:

A. Excessive kidney retention of salt and water : Any extra amount of water or salt in the body will be taken out by the kidneys, so that retention will increase the volume of plasma in the vascular system and in turn will increase the hydrostatic pressure which will lead to the edema.

B. High venous pressure : In Varicose Veins disease ( الدوالي which means that (مرضthe veins especially in the lower limps can't pump the volume of blood inside them to the heart, so the blood will remain in the veins and due to that an increase in the hydrostatic pressure will happen and causes the extracellular edema.

C. Decreased arteriolar resistance:The structure of the vascular system:Aorta ----artery ----arterioles-----capillaries--- venule ---veins. The arterioles are structure of the vascular system which has smooth muscle in it, not as the capillaries which have endothelial structure. Because they have smooth muscles; if the arteriolar resistance decreased, the blood volume in that section will

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be increased , and the blood flow will also increase in the arteriole which will increase the hydrostatic pressure in the capillaries and cause the increase of filtration of plasma and finally cause the extracellular edema.

{In the exam if a question contains a disease in it, the doctor should explain that this disease will increase the hydrostatic pressure}

The second cause of the extracellular edema is Decreased plasma proteins : Which will lead to decrease in the inward forces (oncotic colloid pressure) ,that means the back suction of the plasma into the capillary will be less and the accumulation of the plasma outside will cause the edema-- that if the plasma protein increases it will suck the water from the interstatuim, and if it decreased it will reduce the suction--.

The causes of that reduction are:A. Nephrotic syndrome: where the kidneys start to lose plasma

protein with the urine, so the plasma protein concentration will be lower than before.

B. Wounds, burns will cause the lost of protein with plasma .C. Failure to produce proteins by

1-Liver disease 2. Malnutrition ( تغذية (سوء

When the protein is less the oncotic pressure is less the suction power is less water accumulation outside the capillary is more and that will cause an edema.

In other words (the decrease in the inward forces will cause edema, and the increase in the outward forces will cause edema, too)

The third cause of the extracellular edema is increased capillary permeability :

As we mentioned before, the permeability of the capillary from the Venus part is higher than arterial part, but if the permeability of the whole capillary increases, the amount of water that will leave the capillary will be more.

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The diseases or the abnormalities in which will cause that are:

1- Allergic reactions: where some swellings appear on the person with allergy; that because the permeability of the capillary increases and the plasma leaves to the extracellular compartment.

2-toxins

3- Prolong ischemia:Ischemia is a local lack of oxygen; anemia is a general lack of oxygen.Bed patients; those who don’t move for long period of time will have swellings in their legs which are an extracellular edema due to the prolonged ischemia. After a while this edema will be transfer to an alcer.

The forth cause of the extracellular edema is Failure of the lymphatic system or a blockage in it where it is the responsible part in taking the extra amount of water,so the failure or the blockage of it will lead to return fluids from the interstitium back into the blood, and cause the accumulation of water to cause the swelling(edema). The reasons of that are:

A. Cancer which will block the lymph

B. Infections of parasites (filari) which causes the elephantiasis disease( الفيل mainly in Africa ,where the patient will (داءhave huge swelled legs because there will be small worms(parasites) which only live in the lymphatic vessels so they will block the lymphatic vessels and cause the huge swelling.

C. Surgery; after the surgery when the Surgeon cut random tissues he always cuts the lymphatic vessels in the area of the wound, so there will always be small/medium/large swellings there and that because the lymphatic vessel is not there.

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D. Congenital abnormality of the lymphatic vessels.

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If you sleep at night, when you wake up you should have large amount of edema in your body because when you push your cells on the bed you increase the hydrostatic pressure in them; but thanks God we have safety factors that will prevent edema in our bodies.

In soft tissues just the weight of that tissue with the gravity should create some levels of edema; however fatty people are walking around without edema because of the safety factors.

So if the hydrostatic pressure is 30 mmHg (normal), 33 mmHg, 35 mmHgm, 36 mmHg that will not lead to the Edema. And if the colloid oncotic pressure is 28mmHg (normal), 25 mmHg, 20 mmHg there won't be any Edema, too. The reason behind that, that's the body, has in the interstitial compartment a power which will prevent edema unless the changes exceed 17 mmHg.

The safety factors are:1. Low tissue compliance of the interstitium (you don’t have to go in details)

2. Ability of the lymphatic flow to increase its efficiency 10-50 times more; which means if a small leak in water happened the lymphatic vessel will suck it more because it has the ability to be 50 times more efficient

3. Proteins from interstitium compartment (which create 8 mmHg pressure); if there is increase in them the lymph vessel will be able to take them back to the blood vessels

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The blood

The blood: is a connective mobile tissue that doesn't stand in one area, it is always in a continuous motion, and it is the only mobile tissue in the body, it accounts for 8% of the Total body weight.

The blood is divided into:

1-The liquid part (plasma)2-The cell part (RBCs, WBCs,platlets)

If you take a sample of blood in a tube and do a simple centrifugation, after 3 minutes it will lock like the figure upward; half of it is red in color and the other half is yellow.The red part is the red blood cells (RBCs), on the top of them there is a thin buffy colorless/whitish coat which is the white blood cells (WBCs) and the platelets(fragments of cells)

Hematocrit:  is the percentage of red blood cells compared to the blood volume, which can be measured in the laboratory, and it is about 42% in females & 45% in males.

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Packed cellvolume, orhematocrit

Plasma = 55% of whole blood

“Buffy coat”<1%

Platelets

White blood cells

Red blood cells =45% of whole blood

What is the normal number of red blood cells in the human body ??

5 million cells /micro liter1 mill 1000 μL

So in one ml we have 5 billion RBCs

1 liter 1000 ml and we have 5 liters of blood in the body

So It is about 25 trillions RBCs in the whole body.

The liquid part of the blood (plasma) represents about 55% of the blood volume.

90% of plasma is water and 10% mainly is the plasma protein, electrolytes and other substances.

Functions of Plasma proteins :

1 -Establish an osmotic gradient (oncotic pressure( colloid))

2 -PH buffering (if you drink an acidic juice the plasma protein will interfere within seconds to do the buffering)

3 -Bind cholesterol, iron, and thyroid hormone (as a transporter)

4 -Carry Blood clotting factors (about 13 factors)

5 -Inactivate precursor molecules; (angiotensenogen for example) 6- α-globulins, immunoglobulin, antibodies.

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Erythrocytes""

1 -Red in color.

2-They don’t have nucleus so they don’t live for a long time (the life span of the RBC is 120 days-4 months only-),so in each second our body should produce about 2-3 million cells in order to keep their number constant.

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3-The shape of red blood cells is biconcave (thinner in the middle), and the diameter of it is about 8 μm.

The erythrocyte which doesn’t have a nuclease doesn’t have mitochondria too, but it is full of hemoglobin (consist of globin protein and heme group).It has no DNA or RNA à no protein synthesis for repair, growth, or division.

Each molecule of the hemoglobin contains 4 chains of polypeptide (amino acids sequence) ,2 similar α chains and two β chains that is also similar to each other ,inside these chains we have the non- protein part of hemoglobin which is the heme where the oxygen ,CO2,NO,CO molecules bind.( The figure)

The heme part has a power by which it binds to oxygen, and this power is called (the affinity of hemoglobin)/the efficiency to catch oxygen.

The major function of red blood cells is transporting oxygen from the lungs to tissues in order to feed them with the proper amount of oxygen. The hemoglobin is very powerful (high affinity) in the lungs region where the body need to catch oxygen, and very weak (low affinity) in the tissues region in order to release oxygen there and supply the tissues. (The changes of hemoglobin affinity will be discussed later).

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Polypeptide chain

Polypeptide chainPolypeptide chain

Polypeptide chain

Heme groups

The hemoglobin also can bind to:

1 -CO2

2 -Acidic hydrogen ion portion of carbonic acid

3 -CO

4 -nitric-oxide (NO)

Each cell of the red blood contains 250 millions of hemoglobin molecules which is a huge number that correlates in transporting the huge numbers of oxygen molecules that the body needs to serve it properly.

*250 millions HB molecules /cell

How can you calculate the number of HB molecules in your body?

The # of HB molecules=250 million /cell *5 millions/ μL*1000 μL /ml*1000 ml/liter *5 liters = 625 *10 ^19 molecules.

We don’t use that’s much amount of oxygen, we only use 25% of it (only one fourth of the blood oxygen is used in tissues), while the remaining is used in specific situations where you have to duple, triple, or use ten times more oxygen, so you don’t need to wait for the blood to go back to the lungs in order to supply you with more oxygen .

How the body builds the RBCs??

There is a specific structure in the body that is called bone marrow (red bone marrow),which is the factory of all blood cells. The stem cell in the bone marrow is differentiated either to red blood cells or to white blood cells or platelets. The red bone marrow after the age of 20-25 starts to be a yellow bone marrow rather than red, that's

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mean that the bone marrow will not produce blood cells. However; Even after 25 years you will still have red bone marrow specially in the sternum(the bone in front of your chest),and in the upper and the lower ends of the long bones(legs and hands).

There is a special chemical called erythropoietin, that will be secreted by kidneys only if the body suffers from lacking of oxygen (ischemia) in which the decreased O2 concentration à kidney stimulationà erythropoietin secretionà bone marrow stimulationà increased RBCsà increased O2 concentrationà erythropoietin secretion is turned off.

The decreased amount of oxygen is considered as a signal to stimulate the stem cells production of RBCs.

The End

Done by:Enas Salameh

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Hope for the best, prepare for the worst, fight for what you believe expecting nothing, and you'll never be

disappointed

in all that life throws at you.

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