Blood physiology

for the dentistry students

© Katarina Babinska, Institute of Physiology, FM CU 2020

Blood tests

• a routine examination in medicine

• help to make diagnosis and to treat

Physiology

• studies the function of a healthy human body

• if you know what is normal, you can detect

abnormalities/diseases and treat them

Is the result of the blood test normal?

What is my patient's diagnosis?

Is it an inflammation?

Transfusion for my patient– what blood type?

..........

http://t3.gstatic.com/images?q=tbn:ANd9GcSK0IRJLCYguw

O1YN9x2EA02zYEqub-9-NJ2tnvC9Fh5apPtJnS

Blood Physiology

Lecture 1

Objectives

1. Blood composition and functions

2. Erythrocytes – composition, function, haemoglobin

3. Blood groups – ABO system, Rhesus system

Blood

- plasma (liquid part)

- blood elements (corpuscles):

1. erythrocytes - red blood cells

2. leukocytes - white blood corpuscles

3. thrombocytes - platelets

Each blood component

performs specific functionshttp://www.mountnittany.org/assets/im

ages/krames/176940.jpg

DefinitionRed, opaque liquid that circulates in blood vessels, connective tissue.

What are the main blood components?

1. transportation (from one part of the body to another):

- O2 and CO2 (lungs tissues)

- nutrients (gut – liver/tissues)

- waste products to places of their elimination

- hormones

- immune cells and molecules

- heat (produced mainly in liver, muscles → all over the body)

- medicaments, etc.

Functions of blood

Normal blood volume

7-8 % of body weight

male 6 l

female 4,5 l

2. haemostasis

= bleeding arrest

- components of blood (platelets, clotting factors) are

activated in case of bleeding in order to stop the bleeding

3. Blood generates blood pressure (hydrostatic pressure)

- blood is pressing on the vessel walls

Functions of blood

Erythrocytes – red blood elements

Main function

- transport of the respiratory gasses O2, CO2

Shape: biconcave disc

-advantages of the biconcave shape:

1. larger surface for gas diffusion – by 30% larger than a

ball of the same diameter

2. deformability = erythrocyte can change its shape –

allows to pass through capillaries with diameter lower than

diameter of erythrocyte

Erythrocyte count males 4,3 – 5,3 x 1012.l-1

females 3,8 – 4,8 x 1012.l-1

-the proportion of blood volume that is occupied

by red blood cells

haematocrit =

plasma

leukocytes and

platelets (buffy coat)

erythrocytes

erythrocyte volume________________blood volume

causes a change

in erythrocyte count

a change in blood

volume (plasma volume)

decreased

haematocrit

- anaemias

- chronic blood loss (bleeding)

- kidney disease (anuria)

- after infusion

increased

haematocrit

- living in high altitudes

- excessive Ery production

- dehydration

centrifugation

males 0,39 – 0,49 (39 - 49%)

females 0,35 – 0,43 (35 - 43%)

Normal values

Abnormalities of haematocrit

Blood examination: haematoctrit (PCV-packed cell volume)

Erythrocyte sedimentation rate

-a common examination in clinical medicine

Blood is a suspension (type of solution containing solid particles)

- plasma (water, dissolved substances)

- blood elements - solid particles that are heavier than plasma

- if blood sample is put into a tube

(with anticoagulant to prevent clotting)

- erythrocytes sink to the bottom (because they are heavier)

- leave behind transparent upper layer of plasma

= Er sedimentation

start 1st hour 2nd hour

Normal values (normal FW)

https://www.sarstedt.com/fileadmin/produkte/bilder/_processed_/csm_90.1090_2402_a3f8824e35.png

• blood sample is put into a tube

• reading of the results: after 1 hr, 2 hrs

1st hour

males 2 – 5 mm (up to 15 mm)

females 3 – 8 mm (up to 20 mm)

2nd hour

two times the value in 1st hour or

less (but not more !)

- the most common cause of high

sedimentation rate is inflammation

Haemoglobin (Hb)

- main component of red blood cells

• water 60%

• dry matter 40 %, of that: 95 % is haemogobin

Composition of erythrocytes and haemogobin

Abnormalities in hemoglobin concentration

- anaemia - decreased haemoglobin concentration

- usually associated also with decreased erythrocyte count

males 140 – 180 g.l-1 females 120 – 160 g.l-1

Normal concentration of haemoglobin

Hemolysis

- destruction of the erythrocyte membrane

- haemoglobin is released from erythrocyte

Composition of Hb molecule:

4 subunits, each built of:

• haem - tetrapyrol ring (protoporphyrin IX) with

centrally bound Fe2+

• globin (96% of the molecule)

– chain of amino acids (approx.140)

– according to sequence of amino acids 6 types of Hb

are distinguished:

a,b,,d,e,

– in a molecule of haemoglobin always 2 types of

chains are present - in pairs

http://www.chm.bris.ac.uk/motm/hemoglobin/heme.gif

Haemoglobin

Haem

Composition of erythrocytes and haemogobin

Adult (adults, children over 6 months)

Hb A (2a 2b) - 97,5%

Hb A2 (2a 2d) - 2,5%

Foetal Hb F (foetus, infants up to 6 mo)

(2a 2)

- easier combines with O2 than Hb A

- advantage for the fetus who gets O2 from the

mother through placenta much easier

Embryonic Hb E - present in embryo (1-3 month of

pregnancy

Haemogobin types

Normal

1. Oxygenated haemoglobin (oxyhaemoglobin)

- haemoglobin molecule that carries O2

- binding site for oxygen is Fe2+

oxy Hb_________________

total Hb in blood

arterial blood (rich in O2) 95 - 98 %

venous blood 75 %

2. Reduced haemoglobin (dark red colour)

- after dissociation, non-oxygenated haemoglobin

3. Carbaminohaemoglobin

- carries CO2 bound to – NH2 group of globin chain

Oxygen haemoglobin saturation =

(% of hemoglobin occupied by O2)

Derivatives of haemogobin (forms of hemoglobin in our blood)

2. Methaemoglobin (met Hb): Fe2+ oxidized to Fe3+

- ineffective in transport of O2

- results in hypoxemia/tissue hypoxia (toxic derivative)

- production triggered by oxidizing agents (e.g. some medicaments)

- excessive production limited by an enzyme: met Hb reductase

Abnormal hemoglobin derivatives

1. Carboxyhaemoglobin (derivative of CO and hemoglobin)

- CO competes with O2 for the binding site (Fe2+)

- CO - high affinity to haemoglobin occupies the binding site for O2

air that we breathe – contains 21 % of O2

0,1% of CO in the inspired air - 50 % of Hb occupied by CO (only 50% left for O2 transport)

0,3% of CO in the inspired air - 75 % of Hb occupied by CO (only 25% left for O2 transport)

CO

- present in cigarette smoke - higher concentration in blood of smokers

- may result from incomplete combustion of gas (heaters)

http://www.med-ed.virginia.edu/courses/path/innes/images/rcdgifs/enzyme3.gif

Blood groups (blood types)

Antigens

- substances present in cell membranes (also of Ery)

- determine immunological identity of an individual(different people – different antigens)

- function: resistance against foreign agents

http://upload.wikimedia.org/wikipedia/commons/e/ee/CellMe

mbraneDrawing.jpg

- immune system - can recognize cells with „self“ antigens and does not attack them

- foreign cells (with different antigens) attacking the body - recognized as non-self

and potentially dangerous

http://ib.bioninja.com.au/_Media/self-vs-non-self_med.jpeg

- exposure to non-self antigens - immune response is activated, e.g.

- production of antibodies against this antigen

- or antigen reacts with already pre-synthetized antibodies

- antibody is attached to antigen in cell membrane, subsequently the cell

is destructed by the immune system

strong antigens - fast and strong immune response

weak antigens - weak or no response (low immunogenic potential)

antigen antibody

XEr Er

http://upload.wikimedia.org/wikipedia/commons/e/ee/CellMembraneDrawing.jpg

Presence of antigens in the membrane of erythrocytes

(blood group substances) determines the blood group

Blood type must be considered in:

- transfusions

- transplantations

- gynaecology and obstetrics

Major clinical importance (out of all existing blood systems):

1. ABO system 2. Rh system

- antigens of these systems are strong antigens

(i.e. may cause a strong and rapid immune reaction)

- in case of mismatching transfusion – high risk of

- serious health consequences

- death

GENERAL RULE: IN A TRANSFUSION ALWAYS USE A MATCHING BLOOD

what is a „matching blood“?

http://2.bp.blogspot.com/_mIFBm1eVxx8/SojwvPgHAnI/AAAAAAAAAi0/K19gpgiaz8Y/s400/BloodTransfusion.jpg

- 4 blood types are recognized in ABO system: A, B, AB, 0 (genetically determined, inherited)

- blood group in the ABO system - determined by:

1.Presence/absence of antigen A and/or antigen B

- located in the membrane of erythrocytes

- glycoproteins

- antigens related to blood types are called agglutinogens

2.Presence/absence of antibodies anti A and/or anti B in plasma

- immunoglobulins

- antibodies related to blood groups are called agglutinins

- produced after birth , maximum levels in the adults, then decline in levels

ABO system

antigen A

antigen B

anti A anti B

ABO – blood groups

Blood group

A (48%)

B (9%)

AB (4%)

0 (39%)

A

B

A,B

H

anti B

anti A

anti A, B

absent

substance H is not an antigen

- blood group in the ABO system - determined by agglutinogens and aggluinins

Erythrocytes

Agglutinogen

Antigen

PlasmaAgglutininsantibodies

+

+

recipient (patient) donor

A / anti B B / anti A

recipient (patient) donor

A / antiB A / anti B

=

=

• incompatible blood (mismatched)

• compatible (matching) blood

Blood groups and transfusion

X X

0 – universal donor?

0 +- - -

A B AB 0

+ +

Full blood

Erythrocytes

0 + +

Donor

Recipient

Transfusion

of full blood

A

B

AB

0

A B AB 0

+

+

+

+

-

-

-

-

- -

--

Donor

Recipient

--

-

-

Transfusion of

erythrocytes

A

B

AB

0

A B AB 0

+

+

+

+

-

-

-

--

Donor

Recipient

-

-

+

+

+++

Reaction after transfusion of mismatching blood

• agglutinins react with agglutinogens in Er – agglutination

• possible consequences - more or less serious:

– immune reaction is started

– circulatory shock (breathlessness, pain in the chest, nausea, sweating)

– hemolysis, icterus, kidney failure, death

• symptoms usually occur soon after the transfusion has started

• in this case immediately STOP the transfusion

donor recipient

A / anti B B / anti A

=+

XX

Rh system

1. presence of 3 antigens in the membrane of Er:

(genetically determined) C or c

D or d

E or e

• Rh positivity (Rh+) – 85% of population

– determined by the presence of antigen D

in the erythrocyte membrane

– CDE, CDe, cDe, cDE

• Rh negativity (Rh-) – 15% of population

– d antigen present: CdE, Cde, cde, cdE

Rh-

Rh+

C

c

D

d

e

e

2. antibodies in Rh system - normally not present

However!!!

- D is a strong antigen (all the remaining are weak antigens)

- if Rh+

Er enter blood of a Rh-person, D is recognized as a „foreign“ antigen and

production of antibodies is started

Rh factor and transfusion

Rh negat donor Rh negat patient• the same blood group - matching

Rh posit donor Rh posit patient• the same blood group - matching

Rh negat donor Rh posit patient• matching - „d“ does not trigger

antibody production

donor recipient

Rh posit donor Rh negat recipient

- their production can be triggered if Rh+

erythrocytes enter the blood of a Rh-

individual (e.g. transfusion of Rh

incompatible blood)

A/ 1 st transfusion – no posttransfusion

reaction - no antibodies present in

blood of recipient

B/ Rh+ erythrocytes act as antigen and

stimulate production of antibodies

against antigen D (within weeks) – the

individual becomes sensitized (i.e.

antibodies are present in his blood)

C/ 2 nd transfusion of incompatible Rh+

blood – antibodies react with antigen

D, posttransfusion reaction occurs

(„d“ does not induce production of

antibodies)x

donor: Rh+ recipient: Rh-

Rh+

father + Rh-mother

A/ Rh-foetus - no Rh associated risk

B/ Rh+

foetus – Rh associated risk

1st pregnancy

- circulations of the mother and the foetus are

separated by placenta that is a barrier for Er

- usually no problems with Rh incompatibilty

- in case of complicated birth, accident, etc.

the Rh+ erythrocytes of the foetus may enter the

blood of the Rh- mother

- antibody production against baby's Er is

induced in the mother (even as little as 0,5 ml

of blood may start the Ab production)

- antibodies remain in blood of a Rh-mother

Incompatibility of the blood systems of the mother and the fetus

before pregnancy

after birth

complications at birth

placenta

xNext pregnancies – production of antibodies is even

more higher (problems in about 3% of 2nd and 10% of 3rd pregnancies)

Treatment and prevention

-anti-D serum latest until 72 hours after termination of the

pregnancy (birth, abortion) is given to the mother

-antibodies anti-D from the serum are attached to the Er of

baby (in mother's blood)

-the Er coated with anti -D are destroyed, thus antibody

production by the mother's body is prevented

anti D serum

mother's

blood

baby's

blood

2nd pregnancy (if Rh+

baby)2nd pregnancy

- problems occur if the 2nd baby is also Rh+

- antibodies from mother's blood enter blood of the

foetus through the placenta, attach to baby's Er

- agglutination and haemolysis of Er of the foetus

Consequences

- haemolytic disease of the newborn: anaemia,

hypoxia, icterus-risk of brain damage, death in utero

mother's blood – after birth

x

Other blood systems

- about 30 blood systems exist

- clinically significant:

Kell (K, k) MNSs Kidd

Lewis (Lewisa, Lewisb) Diego Lutheran, etc.

• may cause mismatch of donor´s and recipient´s blood despite compatibility in

ABO and Rh system

• may cause mother/fetus incompatibility

• may cause transfusion reaction in individuals who often receive transfusion

Crossmatching test

- assessment of compatibility between blood of donor and recipient

- blood of both donor and recipient is centrifuged, serum is separated from erythrocytes

- done in 2 steps:

1. major crossmatching test:

serum of recipient mixed with erythrocytes of donor

2. minor crossmatching test:

serum of donor and erythrocytes of recipient

Result:

- no agglutination = blood compatible

- agglutination = mismatching blood

Er DonorEr Recipient

Serum RecipientSerum Donor

+ Bedside verification

+ Bedside – observation of the patient- check for possible symptoms of transfusion reaction:

- dyspnea, tachycardia, sweating, low blood pressure, dizziness, etc.

Blood Physiology

Lecture 2

Objectives

1. Platelets and haemostasis

2. White blood cells and their immune functions

3. Hemopoiesis

4. Blood plasma and osmotic pressure

Dental procedures and bleeding

• a small segment of the population - an increased risk of bleeding

(e.g. inherited bleeding disorders, secondary bleeding due to medication)

• relatively minor invasive procedures can trigger a prolonged bleeding

– distressing for the patient

– hinders the completion of the procedure (e.g., suture insertion)

– can compromise wound healing.

• Dental treatment in bleeding disorders

– a challenge for dentists

• Special management of the patient needed

dental procedures - amongst the most common

invasive procedures

often associated with bleeding - in most cases self-

limiting and non-problematic

Thrombocytes – blood platelets

• cell fragments split from megakaryocytes

• do not contain nucleus

• shape of disc, diameter 2 – 4 mm

• contain cytoplasmic granules, with

substances enhancing the bleeding arrest

Function

• haemostasis - formation of the platelet plug

– blocks the „hole“ in the injured vessel

Normal count

- Thrombocytopenia – lower than normal

count of platelets

150 – 350.109 . l-1

https://encrypted-tbn3.gstatic.com/images?q=tbn:ANd9GcRgdgGtzMdBi5bUqA7_GjQ4ic5NObnrQIuUrOoTgkJWqTzlyvVZ

http://faculty.weber.edu/nokazaki/Human_Biology/Chp%207-blood_files/image014.jpg

Haemostasis – bleeding arrest

- a complex process that makes a bleeding to stop

maintenance of normal blood volume – vital

massive bleeding may lead to cardiovascular collapse and death

- haemostasis includes 3 simultaneous interrelated processes

1/ reaction of the injured vessel

2/ activity of the platelets (platelet plug formation)

3/ blood clotting (haemocoagulation)

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gNE_9HuievzBVNFIM4o0N_rFuR0MGyPK_eezc-Klu_rU8_goQ

1. Vascular constriction

Effects

- a decrease of the vessel diameter

- diminished blood flow through the ruptured vessel

- a decrease of the blood loss

- contraction of the smooth muscle in the vessel wall (circular muscle)

http://images.radiopaedia.org/images/21153/3c503a80bfd516413a65ac8d3aae8d_gallery.jpg

- includes several steps:

A/ ADHESION OF PLATELETS - endothelial lining of vessels - repels the platelets

- vessel injury- endothelial lining is damaged - exposure of subendothelial collagen tissue

- platelets stick to collagen- collagen has receptors for thrombocyte receptors

2. Activation of the platelets - formation of the platelet plug

Injury – platelet adhesionendothelium – repels the platelets

http://asheducationbook.hematologylibrary.org/content/2010/1/387/F1.expansion

B/ CHANGE OF THE SHAPE

platelets swell and become spherical

formation of pseudopods protruding from the surface

- for easier contact with

other platelets

collagen (vessel)

fibrin threads (produced in blood clotting)

C/ THE GRANULE RELEASE

releasing reaction – degranulation

- active substances released from

platelets into the blood enhance

haemostasis

e.g. serotonin, ADP, thromboxane A2 (TXA 2), platelet factors, etc.

http://asheducationbook.hematologylibrary.org/content/2010/1/387/F1.expansion

d/ AGGREGATION OF THROMBOCYTES

- more platelets adhere to each other

Platelet activity results in formation of the platelet plug

- does not contain fibrin threads, therefore loose, fragile

- sufficient for temporary blocking of the bleeding, especially in small vessels

http://asheducationbook.hematologylibrary.org/content/2010/1/387/F1.expansion

- series of enzyme reactions following in definite and rapid sequence

Result of haemocoagulation:

formation of fibrin threads - strengthen and stabilize the platelet plug

network of fibrin threads + platelet plug (+ trapped cells) = blood clot

- blood clot - seals the broken vessel until the tissue is repaired

- blood contains more than 50 substances related to blood clotting

- major role - plasma clotting factors (12 substances)

3. Blood coagulation (haemocoagulation, blood clotting)

https://encrypted-tbn2.gstatic.com/images?q=tbn:ANd9GcSYzcTvcBDveHieyeGqbHSBuVEQa7DocinF5r3gFj32IPSCJIJxKQ

http://www.alphalabs.co.uk/cms/site/images/Page-Header_Coag.jpg

Blood clotting factors

I. fibrinogen

II. prothrombin

III. tissue thromboplastin

IV. Ca2+ ions

V. proaccelerin

VII. proconvertin

VIII. antihemophilic factor

VIII C - antihemophilic globulin

VIII A – von Willebrand factor

IX. Plasma thrombopastin component - Christmas factor

X. Stuart – Prower factor

XI. PTA – Plasma thromboplastin antecedent

XII. Hageman factor

XIII. fibrin stabilising factor

- present in blood (tissues, platelets)

- inactive forms of protheolytic

enzymes (majority)

- blood clotting = a cascade of

chemical reactions leading to their

conversion to active forms

..............

- synthesized in liver

- vitamin K – required for synthesis

of factor II, VII, IX, X

F1 F1A

F2 F2A

•HK - High molecular weight kininogen

•PK - Prekallikrein

1. exposure of collagen in the vessel

wall (when endothelium is damaged)

activates

intrinsic pathway of blood clotting

2. Damage of tissues and release of

thromboplastin from damaged

tissue (tissue factor)

activates

extrinsic pathway of blood clotting

Blood clotting - can be activated by 2 events

intrinsic and extrinsic

pathway converge to

=common pathway

- result: formation of a fibrin thread

http://ahdc.vet.cornell.edu/clinpath/modules/coags/images/primary.gif

INTRINSIC PATHWAY- activated bydamage of endothelial layer

- f. XII

COMMON PATHWAY

EXTRINSIC PATHWAY

- activated bydamage of vessel wall and extravascular tissue- f. III

III

(III)

INTRINSIC PATHWAY- activated bydamage of endothelial layer

- f. XII

EXTRINSIC PATHWAY

- activated bydamage of vesel wall and extravascular tissue- f. III

III

(III)

INTRINSIC PATHWAY- activated bydamage of endothelial layer

- f. XII

EXTRINSIC PATHWAY

- activated bydamage of vesel wall and extravascular tissue- f. III

III

(III)

1. fibrin monomer

2. fibrin polymer

3. cross-linked fibrin polymer

4. stabilization of the cross

linked fibrin polymer

Blood clot

network of fibrin threads running in all directions

- adhere to damaged surfaces of vessels

contains aggregated platelets

(also other blood elements)

in 20 - 60 minutes after formation the clot

retraction takes place

- liquid (serum) is extruded from the clot

- wound surfaces are drawn together,

tissue repair is promoted

clot

clot

serum

Deficiency of clotting factors

VIII C – haemophilia A (classical)

• blood clotting is slowed down (various degrees of severity)

– prolonged spontaneous or traumatic bleeding, blood in urine, within joints, etc.

– even though platelets function normally!!

http://2.bp.blogspot.com/-S6sA_7cvDVA/T8_OWVHjJuI/AAAAAAAAEcI/D5n6wj49YP0/s1600/Hemofilia+(1).jpg

Other types of haemophilia

VIII A – von Willebrand disease

IX – haemophilia B (Christmas disease - rare)

4. Fibrinolysis (dissolution of the clot)

The clot can follow one of two courses:

A/

- it is invaded by fibroblasts

- connective tissue is formed (in 1-2 weeks)

B/

- dissolution of the clot - fibrinolysis

- the clot is dissolved – allows for re-opening of the vessel

- starts about 24 h after bleeding has been checked and tissue repair is underway

- plasmin (plasma protein) – the main component of fibrinolytic system

- plasmin is formed from inactive plasminogen and breaks down fibrin and otherclotting factors

A

B

• abscess - cavity filled

with pus, inflammation

• pus – fluid containing dead white

blood cells and cellular debris

• periodontitis –

inflammation

Leukocytes – White blood cells (WBC)

– main cells of the immune system - „mobile units“

Immunity and the oral cavity

- oral cavity - continuously subject to challenge by the external environment and

foreign material

- teeth disorders - may be associated with infections

- lack colour („white“), become visible after

staining (e.g. the Pappenheim method)

Function

– defence against foreign material - „seek out and destroy“

– main cells of the immune system - „mobile units“

transported by blood to all parts of the body

they are able to move from blood into tissues

(and spend here most of their lives)

Normal count

Leukocytes – White blood cells (WBC)

adults, children 4 - 10.109.l-1

- abnormal (production of new Le)

• infection, inflammation

• intoxication

• cancer

• allergy

Leukocytosis – higher than normal Le count

- normal (WBC released from stores)

• after meal (postprandial)

• heavy physical activity

• emotional stress

• pregnancy

- the count of any type of WBC can increase - neutrophilia, lyphocytosis ....

Leukopenia – lower than normal WBC count

• some diseases (e.g. in immune disorders)

• side effect of some medicaments

adults, children 4 - 10.109.l-1

- throughout the day

minimum in the morning

maximum in the afternoon

Leukocyte count varies throughout the day or in health and disease

Leukocytes include several types of cells

• granulocytes

-specific granules (vesicles)

-lobulated nucleus - polymorphonuclears

1. neutrophilic 56 -64%

2. eosinophilic 1-3%

3. basophilic 0,5-1%

• agranulocytes

-do not contain specific granules

-mononuclear – simple shape nucleus

4. monocytes 3 - 8%

5. lymphocytes 24 - 40%

Differential white blood cell count (leukogram)

- examination of the % of individual types of leukocytes

- helps to make diagnosis - individual types of Le are involved in different functions

1 2

3

4

5

Properties

• nucleus 1 – 5 segments (lobes)

- number of segments indicates age of the cell

- young cells – one segment („stick“)

- by maturation the number of segments increases

Function

• professional phagocytes (microphages) – ingest and destroy foreign material

• involved in innate immune reactions

• high motility, first line defence – first arrive to the place of invasion (of all WBC)

• weak ability of phagocytosis

• Function

- the defence against parasites

- allergic reactions

Neutrophilic granulocytes (56 – 64 % Le)

Eosinophilic granulocytes (1-3% Le)

Granulocytes - life span

• formation in the bone marrow, mature elements released into blood

• if stimulated (e.g. inflammatory stimuli), they can pass from blood into tissues

through the capillary wall

• life span: 4 - 5 days, then die

• if involved into phagocytosis, they die

afterwards (i.e. earlier than in 4-5 d)

• release active substances:

histamin – causes vascular dilatation – increases blood flow into areas of

tissue damage, facilitates the movement of leucocytes into tissues

heparin – anticoagulant (prevente excessive clotting in immune reactions)

Basophilic granulocytes (0,5 – 1% Le)

- largest blood elements, kidney-shaped nucleus

Life fate

in blood 10-20 h

from blood - migrate into tissues here maturate and transform to macrophages

Macrophages - function:

- professional phagocytes (innate immunity)

- antigen presenting cells – cooperate with lymphocytes in adaptive immunity

free macrophages – actively move in tissues

fixed macrophages – in the sites of potential invasion of the pathogens

- e.g. skin (histiocytes), lungs, liver, lymph nodes

Monocytes (3 – 8% Le)

recirculation of lymphocytes

- large round nucleus, narrow cytoplasm

- recirculate

Types and functions

- acquired (specific) type of immunity

- T-Ly (produced in thymus)

- B-Ly (produced in the bone marrow)

-non specific (innate) immunity

- NK cells (natural killers)

Life span: years

Lymphocytes (24 – 40% Le)

blood

lymphatic tissueslymphatic vessels

Defensive properties of leukocytes

diapedesis – ability to squeeze and pass through the capillary wall

amoeboid motion – active movement in tissues, the cell projects

protoplasmic extensions and follows them

chemotaxis – direction and speed of movement influenced by chemical

substances (i.e. produced in the focus of infection)

tigmotaxis – tendency to stick to solid surfaces

phagocytosis (especially neutrophils and macrophages)

http://www.gluegrant.org/images/chemotaxis.jpg

http://3.bp.blogspot.com/_n8DPzZtYzAQ/TJ3h2MVoIZI/AAAAAAAAAAw/MHjsQTESQlM/s1600/10.png

White blood cells and immunity

Immunity

- capacity to resist foreign substances that tend to damage tissues and organs

- microorganisms

- molecules

- own abnormal cells (cancer cells, infected and old cells)

- function performed by the immune system

Immune system

- organs positioned throughout the body

(thymus, lymph nodes, lymphoid tissue in gut, spleen, etc.)

- white blood cells - main cells of the immune system

Immunity

1. innate – non specific

2. acquired (adaptive) - specific

- develops after birth when the body is first attacked by a foreign substances

1. Innate immunity (defense mechanisms present from birth)

Characteristics

• the immune response is non-specific

= it is not targeted at a specific agent (e.g.bacterium),

is rather the same to different agents

• early type of immune response x x x

http://3.bp.blogspot.com/_n8DPzZtYzAQ/TJ3h2MVoIZI/AAAAAAAAAAw/MHjsQTESQlM/s1600/10.png

Type of leukocyte Mechanism of innate immunity

Neutrophils (microphages)

and monocytes (macrophages)

- phagocytosis

Eosinophils - defence against parasites

- phagocytosis (weaker)

Basophils - release histamin – vasodilation and increased permeability

of capillaries (WBC can easier reach tissues)

- release heparin, prevents undesirable haemocoagulation

NK cells (lymphocytes) - recognize absence of “self ” antigens, detect and kill virus

infected cells, tumour cells

2. Acquired (adaptive) immunity (developed throughout the life)

B/ Passive immunization

• transfer of antibodies from exogenous source (e.g. from an immunized donor to a patient, from mother to a newborn via the breastmilk)

• temporary protection (weeks) - no active response of the immune system

A/ Active immunity

- developed in the body after exposure to

a foreign antigen (by an infection, vaccination)

– after first contact with foreign antigen

a weak immune reaction occurs

– in next contact the response is strengthened

(principle of vaccination)

- active response of immune system of a host

- this immunity is permanent

Active immunization - vaccination

- vaccines contain weakened or dead microbes, that trigger an immune response ad

- active immunity develops

http://www.uic.edu/classes/bios/bios100/lectures/memory.jpg

Acquired immunity

• specific = targeted at foreign material that triggered the response

• exhibits immunological memory (permanent immunity)

• mediated by B and T lymphocytes

Naive (virgin) cells

• B and T lymphocytes before they „meet“ the antigen

Effector cells

• lymphocytes, that were activated

by an antigen (who carry receptors for that specific antigen)

Memory cells

• lymphocytes that were once activated can „remember“ the foreign agent

• after repeated contact with that particular antigen they can produce clones directed against the antigen

http://ars.els-cdn.com/content/image/1-s2.0-S1471490606001220-gr1.jpg

http://bthsbioteacher.wikispaces.com/file/view/43_12ClonalSelection_L.jpg/33997473/463x451/43_12ClonalSelection_L.jpg

- additional functions of some T-lymphocytes

• TH (helper)

- required for activation of B-Ly

• T regs (formely suppressors) – modulate the immune response, shut down the

immune response after it has achieved the goal

T-lymphocytes

- formation in bone marrow, maturation

in the thymus

- exhibit cell mediated immunity –

• TC (cytotoxic) – directly kill foreign

cells by releasing substances that

attack their cell membranes (make „a

hole“ in the membrane)

http://www.anselm.edu/homepage/jpitocch/genbio/helperTkill.JPG

Effector cells of acquired immunity

Effector cells of acquired immunity

B-Lymphocytes

- formation and maturation in bone marrow

- mediate humoral type of immunity

B-Ly after recognizing the foreign agent - transform into plasma cells

acivation requires cooperation with T-helper lymphocytes

plasma cells produce specific molecules of antibodies (immunoglobulins):

Ig M Ig A Ig G Ig D Ig E

antibodies bind to the foreign agent (e.g. the bacteria)

and mark it for destruction

(by phagocytosis or by other mechanisms) X

Hematopoiesis

Life span of formed blood elements

erytrocytes 120 days

granulocytes 4 - 5 days

monocytes weeks/months

lymphocytes months/years

thrombocytes 8 – 10 days

Hematopoiesis

- production and development of the blood elements

- maintenance of normal count of formed elements in blood

a neonate, small child- hematopoiesis in all bones

an adult- flat bones- vertebrae- epiphyses of humerus, femur

totipotential stem cell (progenitor)

hematopoietic (myeloid) lymphopoietic

erythroid megakaryocytic myelomonocytic B-Ly T-Ly

myeloblast monoblast

Development of blood elements – blood cell lines

Multipotential

stem cell

Common

progenitor

stem cells

Unipotential

cells

Lineages

(Series)

- involve several

stages of

development red blood

cells thrombocytes granulocytes monocytes

B-Ly T-Ly

Ne Ba Eomyelocyt

stem cells – able to divide by mitosis, stores are continuously replenished

unipotential cells – maturate into predetermined cells (colony forming units)

ERYTHROPOIESIS

Formation of red blood cells

• Pronormoblast

• normoblast

- basophilic

- polychromatic

- ortochromatic – expells the nucleus

• reticulocyte

- immature erythorcyte

- in small counts present in blood

- lacks nucleus

- matures in blood

• erythrocyte – mature element without nucleus and organelles

bone

marow

blood

Substances for erythropoiesis- provided by diet - nutrients

amino - acids

iron

A/ food derived - Fe3+

B/ recycled – from destroyed erythrocytes

* deficiency – hypochromic anemia

copper (plasma ceruloplasmin – stores)

- helps in utilisation of iron stores

* deficiency – hypochromic anemia

cobalt

vitamin B12 – extrinsic factor

- it can be absorbed in small intestine only if bound to intrinsic factor

produced in gastric mucosa

folic acid

- synthesis of DNA, erythrocyte maturation

* deficiency of B12 or folate – pernicious anaemia (megalocytic)

Regulation of erythropoiesis

erytropoetin

– a hormone produced in kidneys – glomerulus (mesangium)

effects of erythropoietin

• stimulates the stem cells, differentiation and release of erythrocytes into blood

erythropoietin

production

- stimulated by

hypoxia

- anaemia,

- high altitudes

- lung diseases, etc.

source:

http://wdict.net/img/erythropoietin.jpg

• production of Ery: bone marrow

• life span: 120 days

• destruction of Ery: spleen (cords of the red pulp, sinusoids – narrow spaces)

Hemoglobin break-down products

• iron (haem) and peptides (globin) - recycled and used for formation of new Ery

• bilirubin = product of breakdown of haem, normally present in blood in low

concentration – excreted in bile

• icterus (jaundice) - caused by excess of unconjugated bilirubin in blood

- yellow colour of the skin and sclera

Life span of red blood cells

Blood plasma

- tekutá zložka krvi svetložltá

priehľadná tekutina,

- 4-5 % telesnej hmotnosti

Body fluid compatments (as % of body weight)

Total body fluids 60%

1. intracellular (ICF) 40%

2. extracellular (ECF) 20%

- intravascular (plasma, lymph) 4 - 5%

- interstitial (among cells in tissues) 15%

- transcellular 1 %

(intraocular, synovial, pericardial, peritoneal, cerebrospinal fluid, etc.)

- ECF and ICF differ in ion composition

Main ions in - extracellular fluid: Na+, Cl-, HCO3

-

- intracellular fluid: K+, PO4-

sušina

15 %

1%

4 % 40 %

40 %

ICT

ECT ECF

ICF

dry matter

- liquid part of blood, component of the body fluids

Properties: transparent yellow fluid (separated from blood by standing or by

centrifugation), pH 7,4

Constituents:

- water 90 %

- dissolved substances – solutes 10 %

1. organic – plasma proteins

2. other organic substances

3. inorganic

total protein proteinaemia 60 - 80 g .l-1

fractions albumin

globulins (a1, a2, b, )

fibrinogen

1. PLASMA PROTEINS

- produced in liver (except gamma globulins produced by the lymphocytes)

Composition and amount

Functions:

carriers for other molecules

- bind and transport substances (e.g. lipids, Fe, hormones, drugs, etc.)

blood clotting - plasma clotting factors

immune functions – immunoglobulins, complement

role the sedimentation rate

contribute to blood viscosity and normal blood flow

maintenance of constant pH of plasma

- protein buffer – can bind excess acids/bases, thus balance the pH of blood

nutritional role – rapid supply of amino-acids for tissues

generate the colloid – osmotic pressure

2. OTHER ORGANIC SUBSTANCES IN PLASMA

- include many different substances

glucose

lipids, cholesterol, triglycerides

non-protein substances containing nitrogen - creatin, creatinin, urea, uric acid

bilirubin, hormones, vitamins, etc.

- typically constant plasma concentration, e.g.

- their plasma level indicates function of various organs or systems

• hormone levels-endocrine system • creatine-kidneys

• bilirubin-liver • glucose-pancreas, etc.

Function

• influence physical and chemical properties of plasma, e.g.

- pH

- osmotic pressure,

- constant volume etc.

• role in various biologic processes, e.g.

- buffering

- permeability

- blood clotting, etc.

Serum = plasma without fibrinogen and some other clotting factors

3. INORGANIC SUBSTANCES IN PLASMA

Main cations:

sodium, calcium, potassium, iron, magnesium, copper, iodine

Main anions:

chlorides, bicarbonates, phosphates

-plasma (but also all body fluids) contains dissolved substances that are osmotically

active and give rise to osmotic pressure

Osmosis - diffusion of solvent through semipermeable membrane from space with

lower concentration of solute into the space with higher concentration

- semipermeable membrane - permeable only for solvent, not for dissolved

substances

Osmotic pressure – water (solvent) passes the semipermeable membrane under

pressure called osmotic pressure

- the bigger the difference in concentration, the higher is the osmotic pressure

selectively permeable membrane

Osmotic pressure of blood plasma

lower concentration higher concentration

vodap

water

- normal value 690 kPa

- depends on concentration od osmotically active substances

- osmolarity of plasma = concentration of osmotically active substances:

290 - 300 mmol.l-1

- osmotic forces are generated by mainly by Na+, Cl-, glucose, albumin

Osmotic pressure of blood plasma

Some functions in human body are based on osmotic pressure, e.g.:

• regulation of water balance - hypothalamus monitors osmolarity of plasma

• absorption in gut

• water reabsorption in kidney

• osmotic pressure needs to be considered when patient is given an infusion, or in

laboratory experiments with blood

- blood plasma and blood elements – are isoosmotic (isotonic)

= osmotic equilibrium – no water gain/loss

water plasma

690 kPa

isotonic

hypertonic

hypotonic

Osmotic resistance of erythrocytes – the ability to

resist small changes in osmotic pressure

lysisisotonic hypotonic more hypotonic

A/ Isotonic solutions

– the same osmotic pressure as plasma, optimum for function

of Ery

B/ Hypertonic solutions

– higher osmotic pressure

– if a cell („isotonic solution“) is put into a hypertonic solution,

it loses water, shrinks and may malfunction or die due to

rupture of its membrane (haemolysis)

C/ Hypotonic solutions

– lower osmotic pressure

– water flow is directed into the erythrocyte

– cause expansion of cells, their malfunction and eventually

destruction and death (haemolysis)

- a component of osmotic pressure

- exerted by plasma albumins

- normal value: 3,7 – 4 kPa

(out of 690 kPa of the total osmotic pressure)

proteinwater

tissue blood capillary

Function:

- plays role in water exchange in capillaries

- it exerts reabsorption pressure in capillaries – that allows the return of

water from tissues into capillaries

- it prohibits water loss from circulation

- main factor for maintenance of constant blood volume

Oncotic pressure (colloid-osmotic

pressure of plasma proteins)

1. are permeable for low molecular weight

substances (e.g. ions)

- ions can freely cross the capillary membrane in

both directions (tissue - capillary)

therefore

- the osmotic pressure of low-molecular weight

substances in capillaries = 0

- no net changes in water volume

Na+

Cl-

HCO3-

proteins

Na+

Cl-

HCO3-

proteins

tissue blood capillary

2. are impermeable for plasma proteins (macromolecules)

- plasma proteins exert oncotic (colloid-osmotic) pressure on capillary wall

- concentration of proteins in plasma >> concentration of proteins in tissue fluid

- water moves from tissues (interstitial fluid) into capillaries

Blood capillaries

Capillary filtration and reabsorption (effect of blood and oncotic pressures)

• arterial end of capillary- filtration

- water moves from capillary into interstitial spaceblood pressure + oncotic pressure of interstitial fluid > oncotic pressure of plasma + pressure of interstitial fluid

• venous end of capillary - reabsorption

- water moves from interstitial space into capillariesoncotic pressure of plasma + pressure of interstitial fluid > blood pressure + oncotic pressure of interstital fluid

- normal concentration of plasma protein level – maintenance of constant blood volume

- hypoproteinaemia (e.g. due to starvation, liver diseases, kidney disease) - oedema

tissue

capillary

oedema

filtration reabsorption

hypoproteinaemia

tissue

capillary