Physiology, Lecture 5, Blood (Lecture Notes)

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Physiology lecture 5 – 6/10/2010 Done By: Lamees Nimri

Blood is a connective mobile tissue which has cell compounds (45%) & liquid parts (55%). The majority of cell compounds are RBCs which have a major function in carrying oxygen from lungs to the tissues. The liquid part is plasma which consists of 90% of water , 10% different substances mainly proteins (6-8%) that perform many valuable functions; some proteins like gamma globulins are antibodies ,other proteins share in the colloid osmotic pressure ,some of them carry insoluble substances like cholesterol & vitamins. the number of RBCs is 5 million/μL and the life span for them is 120 days so they must be replaced at the rate of 2-3million/sec. the factory for RBCs production is the bone marrow which can be stimulated by a special hormone or chemical called erythropoietin that secreted form the kidneys by the lacking of oxygen. In the stem cell the mother cell is one but it can be RBC, WBC or platelet.. the red bone marrow produce RBCs and agranulocytes WBCs like momocytes and all types of granulocytes WBCs . The other type of WBCs is the lymphocytes ,they're produced in the lymph nods but their stem cells are produces in the bone marrow after that they will be migrated from the bone marrow to the lymph nods then it'll be located there and start to produce the lymphocyte cells for the blood circulation.

Platelets are the other part of blood ,they aren't complete cells but small cell fragments. The big cell is called the megakkaryocyte which is located in the bone marrow ,It's the differentiated cell for platelets that came from the mother stem cell,it has a large volume after that it will be fragmented into pieces which migrate form the bone marrow to the blood circulation we call them "Platelets" or thromocytes. The number of platelets in blood is about 150-350thousand/mmThey live only 10 days then the bone marrow will produce more and more.

*Hemostasis:Is the process by which you prevent bleeding from a broken blood vessel. It has 3 steps :-Step 1: spasm to the vessel which cause the muscles to contract in order to reduce blood flow and prevent blood lose also the endothelial surfaces of the vessel are pressed together when the contraction happens and this speeds the process of healing.

-step 2 : platelet plug formation

Fig. 11-7, p. 322

Platelet

Vessellumen

Vesselwall

Adenosinediphosphate(ADP)

Prostacyclinand nitric acid

Normal endothelium

Inhibits plateletaggregation

Normal endothelium


CollagenAggregatingplatelet plug Exposed collagen

at site ofvessel injury



Normal endothelium

CollagenExposed collagenat site ofvessel injury


Normal endothelium




Normal endothelium





Normal endothelium


Normal endothelium




Normal endothelium


Aggregatingplatelet plug

Normal endothelium




Normal endothelium



Normal endothelium




Normal endothelium



Normal endothelium




Normal endothelium


Whenever there's a damage in the endothelial structure in the blood vessel will cause an exposure of a special protein called collagen in the interstitial compartment that stimulates a huge number of platelets to be adherent to each other as shown in the figure above.

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These platelets are flowing in the blood circulation normal but if there is a cut or damage the collagen will attract these platelets together to form platelet plug, this plug will produce different chemicals the main one is Adenoslne diphosphate (ADP) which will cause more aggregation of platelets so if we have 1 million platelets together ADP will be produced and that will cause another million to be in that area and the plug will be more and more through positive-feedback mechanism. If the plug will continue to develop it will block the whole capillaries,to prevent that there're another chemicals to released from the adjacent area of endothelial cells ,these chemicals are: prostacyclin and nitric oxide.

So In the local area of the wound there're chemicals to increase the plug but aside that area there're chemicals to prevent the plug. If plug formation is enough to close the wound and form a new endothelial tissue the third step will not occur, but if the bleeding continue the third step will occur which is called " clot formation " .

-step 3 : Clot Formation

The ultimate step of that series of reaction is to change fibrinogen (soluble plasma protein) to fibrin which is like needle network of threads and it'll form a clot. There're 12 plasma clotting factors that circulating in the plasma in inactive form but if there's any damage in the endothelial cells or the smooth muscles or the tissue that will produce chemicals from the damaged area that will activate factor number 12 which will activate factor number 11 and so on through the positive-feedback mechanism .

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Inside our vascular system there're 2 major pathways to clot formation: the intrinsic pathway & the extrinsic pathway.

The intrinsic pathway: occurs inside the vessels or outside the body for example if we took blood sample and put it in a tube if we don't add anticoagulant factor to that tube it'll be clotted through the intrinsic pathway even it's outside the body. Inside our body if there's a cut wound or any damage in the endothelial structure that will activate the intrinsic pathway. When the area has a damage but the blood leaves outside to the interstitial compartment (under the skin ) which is called hematoma it'll follow the other pathway which is the extrinsic pathway because it's outside the vessel.

The intrinsic pathway: This pathway is set off when factor XII (factor number twelve) is activated by either exposed collagen in an injured vessel or a foreign surface such as a glass test tube after that factor 12 will activate factor 11 and factor 11 will activate 10 and factor 10 will activate factor 9 ,this positive-feedback will lead to the conversion of prothrombin to thrombin this is the major protein which is able to cut the fibrinogen and form the fibrin after that factor XIII ( factor thirteen) which is called fibrin stabilizing factor will solidify the clot.

For example, when we have a wound and the clot forms at first it'll look yellow a little bit but after a while it'll be brown .when fibrin forms in the wounded area it'll collect within it different things mainly RBCs and a serum which has no clotting factors that makes the clot soft and not dry and fixed that's why when kids play with there wounds they would take it back again which cause another bleeding but after a while factor 13 will make the clot solid and by the contraction of elastin and other proteins this will cause to squeeze the serum out so we will end with a dry clot and that will be the solid fixed brown clot.

After the bleeding stop there're some chemicals to contract that clot (the contraction starts from the peripheral to the central part to close the wounded edges together which speed the healing process of producing connective tissue and a scar is formed ). There're two ways by which the colt is taken off from the wounded area :- phagocytic cells which eat the dead cells

- cutting the fibrin by another chemical called plasmin which is in inactive form (plasminogen) in the plasma when there's a need to it the plasminogen will convert to plasmin that will dissolve the clot.

Under normal condition there is another system inside blood vessels which is called antigoagulant mainly the plasminogen all the time plasmin fights and forms clot inside the body but under ubnormal conditions like thromboembolism ; thrombus means the clot which blocks the whole vessel for example infarction in the heart, stroke in the brain, Deep vein thrombosis (DVT) in the lower limbs. embolism is a free-floating clot that moves with the blood but it's small and doesn't clot the whole vessel, both situation are dangerous for the life but if there is a good antigoagulant system they sould not be exist.

The main causes for thromboembolism:

1-rough surface for the endothelial layer which is so smooth so the blood slips over it without any trouble but by aging or by being very fat that will create a lot of cholesterol inside the plasma which cause a very rough surface for the endothelial layer and make disturbance of the blood flow which might cause infarction or stork.

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2- imbalance between clotting and anti-clotting system: if there's more activation in fibrin,thrombin and factor 13 and there's less plasmin effect that will cause clotting formation inside the vessel

3-slow blood flow: if it's normal the platelet won't be aggregated if it's slow the platelets will be adherent to each other and the plug will be formed and this will activate the positive-feedback mechanism and this will cause the clotting formation.

4- thromboplastin is the triggering point of the extrinsic pathway for clot formation,whenever the tissue is damage the thromboplastin will be released when it's released in the tissue it will cause the clotting outside the vessels through the extrinsic pathway but if it's caused by a huge damage of the tissue it'll be distributed inside the vascular system which might cause a clot inside the vessels which cause thrombus or emboli.

*leukocytes (WBCs) :

There are two groups of them: granulocytes with granules and agranulocytes without granules.-Agranulocytes are 2 types: monocytes (the biggest one) and lymphocytes which are mononuclear -granulocytes are 3 types : basophils, eosinophils, neutrophis ( the major amount 60-70%)

WBCs is colorless so in order to distinguish them we use special stains ,basophils will be blue in color because it's basic and eosinophils will be red and neutrophile will be in between.All of them play a major roll in the defense mechanism in different ways either by releasing toxins that makes holes in the viruses and bacteria or by producing antibodies or by killing invader itself.

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*Respiratory System :

Our life is started by the fist inspiration, if the new born doesn't cry we don't conseder that new born is alive so the first cry is the first respiratory movement which is the first sign in our life and the last movement in our life is the last expiration Respiratory sysyem is one of the most efficient system in our body but it doesn't need a lot of energy to achieve its function (2-3 % of the total energy consumption in the normal condition.) this small percentage is for gas exchange, breathing(ventilation) and so on.

There're 4 steps in respiration the first one is called respiratory cycle which has 2 phases; inspiration and expiration , inspiration to take the air from the atmosphere to the lungs and expiration to take off carbon dioxide form the lungs to outside the body.the second step is to conduct gas exchange between the alveoli in the lungs and the blood (take oxygen from lungs to the blood and remove CO2 from the blood to the lung) .the third one is called gas transport in which O2 and CO2 is transported by the blood between the lungs and the tissues. The final step is the diffusion of gases through the capillaries to the tissues. These 4 steps are for external respiration but the internal respiration "cellular respiration" refers to the intracellular metabolic processes carried out within the mitochondria when the O2 is inside the cells which use nutrients and O2 to get energy and CO2.

There're many non-respiratory functions for this system like:

- when the breathing occurs water vapor will get inside and outside the body so the temperature is regulated plus the body compartment will remain constant ( we will keep the alveoli wet )

- enhances venous return: the heart pumps the blood out and this blood should go back to the heart but this isn't easy because the veins don't have enough muscle to pump the blood back so there're some other structures and other functions from other systems like the negative pressure inside the chest which cause a suction for the blood to flow inside the veins and get back to the heart.

Fig. 12-1, p. 366

Atmosphere

Tissue cell

Alveoli of lungs

Pulmonarycirculation

Systemiccirculation

CO2O2

Food + O2 CO2 + HO2 + HTP

O2

CO2

CO2

O2

1

Steps of external respiration

Ventilation or gas exchange betweenthe atmosphere and air sacs (alveoli)in the lungs

Exchange of O2 and CO2 between airin the alveoli and the blood

Transport of O2 and CO2 between thelungs and the tissues

Exchange of O2 and CO2 between theblood and the tissues

Internal respiration

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3

4

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- acid-base balance

- enables speech: without the respiratory system the vocal cords (which give sounds by flowing in and out the air) will not work .

- defends against foreign inhaled matters ( dust, smoke, viruses, bacteria) by phagocytes .

- smelling: without breathing we can't smell because the movement of air will cause particles to dissolve in special receptor to smell them.

- Shape of the chest

- Protects heats and vessels :the lungs protect the hearts and vessels in addition to the chest bones

- Aireate the blood between respiratory phases.

The respiratory system includes: the respiratory airways leading "conducting channels" which conduct air into the lungs where gas exchange occurs and the chest which involves in producing movement of air through the airways into and out of the lungs.

The lungs consist mainly of alveoli ( 300 million of them each about 300 micrometer in diameter) in order to increase the surface area (75 meter square).

The Alveoli are clusters of thin-walled, inflatable, grapelike sacs which are connected with each other . The alveolar walls consist of single layer of flattened type 1 alveolar cells. The alveolar epithelium also contains type 2 alveolar cells which secrete surfactant a chemical complex, there are also the phagocytes which take off invaders.

Fig. 12-2b, p. 367

Terminalbronchiole

Respiratorybronchiole

Branch ofpulmonaryartery

Alveolus

Pores of Kohn

Smoothmuscle

Branch ofpulmonaryvein

Pulmonarycapillaries

Alveolarsac

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The blood circulation around alveoli is very efficient to take the O2 the red one is the venous part which takes oxygen-rich blood from lung to the heart and the blue one is the arterial part which is CO2-rich blood.

Airway conducting channels start with a big trachea (the cartilaginous structure with some muscle in it) then it goes to the right bronchus and left bronchus, the 2 bronchus will be divided into 4 and the 4 to 8 ….until 25 divisions occur after that we reach to the final parts of the airway conducting channels which are called the bronchioles, they're small and have smooth muscles (the brownish structure) ,if the muscles contract the airway channels will be squeezed if the muscles relax the airway channels will be dilated.

For the protection of the lungs there's another special structure surrounding the lunges which is called the pleural that has double layers outside layer which is connected to the internal surface of the chest (to the ribs and muscles), inside layer connected to the alveoli .in between there's a pleural space and it isn't open neither to the lungs nor to outside the chest ,it contains a small amount of pleural liquid it's like plasma and it lubricates the movement of the lungs .because of the liquid the separation of the two layers won't be easy but they can slide over each other .if there's a deficiency in that liquid the breathing will be painful.

Respiratory mechanism :

Air tends to move from a region of higher pressure to a region of lower pressure .there are three different pressures which are :1- the atmospheric pressure: the normal pressure at the sea level is 760mm Hg if we go up it will

decrease and if we go down it will increase 2- intra-alveolar pressure is the pressure within the alveoli 3- the intrapleural pressure it's within the pleural sac.

Fig. 12-5, p. 370

Atmosphere760 mm Hg

Atmospheric pressure (the pressureexerted by the weight of the gas in theatmosphere on objects on the Earth’s surface—760 mm Hg at sea level)

Intra-alveolar pressure (the pressure withinthe alveoli—760 mm Hg when equilibratedwith atmospheric pressure)

Intrapleural pressure (the pressure within the pleural sac—the pressure exerted outside the lungs within the thoracic cavity, usually less than atmospheric pressure at 756 mm Hg)

Airways

Thoracic wall

Plural wall

Lungs

756 mm Hg

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Because the lungs is connected wit the conducting channels so when these channels is opened to the outside there will be a communication between the atmosphere and the alveolar space and the air will flow from higher to the lower pressure .without doing inspiration and expiration the alveolar pressure will be equaled to the atmospheric pressure (760mm Hg) . but when inspiration occurs the pressure inside the lungs is less than the atmospheric pressure. Through expiration opposite thing occurs the air moves from lungs to outside so the alveolar pressure is higher than the atmospheric one.

760mm Hg is considered as zero line ( 0 pressure = 760mm Hg ). Through inspiration inside the lung the pressure will be negative ( not negative in the absolute but in the concept) .for example if the alveolar pressure is 757mm Hg and the atmospheric pressure is 760mm Hg this means -3 ,Inside 762 and outside 760 it means +2 .The intra-alveolar pressure could be zero, + ,- depending on the movement of the air but the intrapleural pressure it's about -4 (less than atmospheric pressure ) it could be changed (more negative).

*Respiratory Muscles:

In inspiration to increase the chest cavity there're special muscles called inspiratory muscles the main are the diaphragm which is under the lungs in the chest cavity when it's contracted it will go down and it will increase the space of the chest. The other main muscle is the external intercostals between the ribs these muscles when contract it will raise the ribs up. that will increase the chest's dimension in all directions (up and down) and anterio-posterior.The accessory inspiration muscles are: sternocloidomastoid and scalenus which located in the neck these kind of muscles is used in exercising and in stressful situation.

In expiration the muscles are relaxed so it pushes the air outside .the expiration musles are the internal intercostals and the abdominal muscles.in forceful breathing huge contraction will occurs during inspiration so the relaxation of the muscles during expiration isn't enough so the expiration musles will contract.

Fig. 12-11a, p. 374

Externalintercostalmuscles(relaxed)

Contractions of external intercostalmuscles causes elevation of ribs,which increases side-to-sidedimension of thoracic cavity

Lowering of diaphragm oncontraction increases verticaldimension of thoracic cavity

Elevation of ribs causes sternumto move upward and outward, which increases front-to-back dimension of thoracic cavity

Before inspiration Inspiration

Elevatedrib cage

Contractionof externalintercostalmuscles

Sternum

Diaphragm(relaxed)

Contractionof diaphragm

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Best of luck all ….study well

Done By : Lamees Nimri

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Physiology, Lecture 5, Blood (Lecture Notes)

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