Lec.1 Hematology

8/4/2019 Lec.1 Hematology

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Pathophysiology PCP 341

Nermien Waly MD, M.Sc., Ph.D.Lecturer

School of Pharmacy

[email protected]

https://sites.google.com/site/nwaly09/
mailto:[email protected]://sites.google.com/site/nwaly09/https://sites.google.com/site/nwaly09/mailto:[email protected]


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What is patho-physiology?

it is the study of the changes of normalmechanical, physical, and biochemicalfunctions, either caused by a disease, or

resulting from an abnormal syndrome.More formally, it is the branch of medicinewhich deals with any disturbances of body

functions, caused by disease or prodromalsymptoms.
http://en.wikipedia.org/wiki/Mechanicalhttp://en.wikipedia.org/wiki/Physicalhttp://en.wikipedia.org/wiki/Biochemicalhttp://en.wikipedia.org/wiki/Diseasehttp://en.wikipedia.org/wiki/Diseasehttp://en.wikipedia.org/wiki/Biochemicalhttp://en.wikipedia.org/wiki/Physicalhttp://en.wikipedia.org/wiki/Mechanical


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Course objectives (ILOs)

1. Understand the basic biological mechanism(s) of diseaseprocesses.

2. Describe the disease manifestation by the way the disease disruptsnormal physiology/anatomy and biochemistry.

3. Determine the impact and abnormal functions upon the organ(s)associated with the disease process of targeted body systems.

4. Develop basic critical thinking skills that correlate the abnormalfunctions of body systems with the disease process.

5. Implement the knowledge of disease development to understand

the treatment rationale.6. Describe the basic concepts of pathophysiology at the cellular,

organ, and system level.

7. Describe clinical manifestations associated with the diseasedorgan(s).


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Why do you (pharmacist to be)study pathophysiology?

Your (Pharmacist) role as a health careprofessional:

1. Traditional pharmacist skills

2. Patient- oriented (clinical) skills


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The role of clinical pharmacist

1. Central clinical pharmacy services

a) Patient education

b) Drug use evaluation and report

c) In service educationd) Clinical trials


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2. Patient specific clinical pharmacy services.3. Role in drug and poison information.

4. Total parental nutrition.

5. Drug counseling

6. CPR

7.Preparation and share of hospital forums,bulletins and news letter.

8. Design and prep of Unit dose drug distributionsystem.

9. Participation in clinical rounds.

10. Crucial health care team member.

11. Role in ICU.

The role of clinical pharmacist


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Basic requirements to practiceclinical pharmacy

Anatomy and histology

Physiology

Pathophysiology Pathology

Interpretation of common clinical lab

results Clinical pharmacology and therapeutics.


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Hematology


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Hematology overview

Objectives Blood physiology Normal blood picture Blood groups and transfusion Blood coagulation Reticulo-endothelial system: lymph nodes and spleen. Pathophysiology of blood diseases:A. Formation (production) disorders1. RBCs disorders: Anaemia, Polycythaemia.

2. WBCs disorders: Leukemia, leukocytosis, &lymphomas

3. Platelets disorders: ThrombocytopeniaB. Functional disorders: Bleeding disorders


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Objectives

To gain knowledge of the following:

1. Blood functions

2. Blood groups and principal of bloodtransfusion.

3. Blood coagulation.

4. To be able to read and interpret blood

picture.5. Understand Pathophysiology of common

blood disorders.


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I. Blood physiology

overview

1. Physical properties of the blood

2. Functions of the blood3. Blood composition: plasma and cells

4. Plasma composition

5. Cells of the blood


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Physical properties of the blood

1. Color: Arterial is bright red, venous isbluish red

2. Specific gravity: 1060 (what is that?)

3. Osmotic pressure: 25-30 mmHg (what isthat?)

4. Viscosity: 5 (what is that?)5. Blood pH: 7.4 arterial is more alkaline

why?p.s. any time a question e.g. what is that ? Arise it means that you should already know

this information and if you do not remember it you should look it up. ThisInformation is part of the course and subject to questions in the quizzes and exams.


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Functions of the blood

1. Transport medium: oxygen, carbondioxide, waste products, activesubstances, heat.

2. Defensive function: WBCs.3. Homeostasis: maintenance of internal

environment.

4. Regulation of body temperature.physically and physiologically.

5. Hemostasis and blood coagulation.


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Blood composition


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Total body weight

8% blood 92% body fluidsand tissues

45% formedelements (hematocrit)

55% plasma

91.5% waterErythrocytes

Leukocytes

Platelets

7% proteins

Salts, lipids, enzymes,vitamins


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7% proteins

55% Albumin 38% Globulins 7% fibrinogen

What is the Function(s) of plasma proteins ?

Homework: Look up at least 2 functions for each plasma protein this will be oneof the questions on your first quiz.


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1. Red blood cells /erythrocytes/ RBCs

4-5 million/l Physiological changes in the number, pregnancy and high altitude. Biconcave, circular, non-nucleated discs 8 micron in diameter 2 micron thick and 90 cubic micron in volume Contents: hemoglobin (34%) water (60%) , carbonic anahydrase,

and electrolytes

RBCs membrane plays an essential role in its function and bloodgrouping. It is elastic, semi permeable, antigenic character.

Blood cells (formed elements/hematocrit)


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Development of red blood cells

Formed in the red bone marrow in adults .

In embryos the liver is the main site of formation.

Life span of 120 days and removed by the spleen.

Reticuolocytes is about 1% in peripheral blood.

Functions of red blood cells: gas transport, bloodgrouping

Pluripotent hematopoietic stem cells


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Factors affecting erythropoiesis

1. Oxygen tension of the blood: lowering oxygentension stimulates erythropoiesis.

2. Erythropoietin3. Diet: protein and iron (ferrous), reducing agents

e.g. vitamin (vit.) C, maturation factors e.g. vit.B12 and folic acid

4. Absorption and transport of iron (transferrin)5. Liver: role in protein synthesis (globin: a

plasma protein) and vitamin storage6. Hormones e.g. androgens7. Bone marrow e.g. radiation, aplasia


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2.White blood cells, leukocytes, WBCs

Leukocytes4000-10,000/microlitre

Granulocytes Agranulocytes

Neutrophils (PMNs) 40-70%

Eosimophils 1-6%

Basophils


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Development of white blood cells

Pluripotent hematopoietic stem cells


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Functions of the white bloodcells

Defense /immunity against infection (viralor bacterial), parasite infestation throughthe following mechanisms:

1. Phagocytosis (neutrophils /monocytes)

2. Antibody formation (lymphocytes)

3. Plays a role in allergic reaction4. Autoimmune diseases


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3. Blood platelets / thrombocytes

These are granular non-nucleated ovalbodies about 2-4 microns in diameter

250,000-500,000/ cubic ml

Origin: megakaryocytes in BM Functions:

1. Hemostasis /blood coagulation

2. Phagocytosis3. Storage and transport


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II. Blood picture

Is a report that shows normal bloodparameters.

Value: an important diagnostic tool for

both blood disorders as well as otherdiseases.

It is important for a health care

professional e.g. doctors, pharmacists,nurses etc.. to be able to read andinterpret a blood picture.


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Home work

1. Form a group of your colleagues to be your permanent study group for thiscourse or the semester (maximum 10 per group)

2. Find a blood picture of a relative and check it. Study the blood picture withyour group and write down your findings. Please give me a copy of theblood picture with your finding and conclusion on a separate page attachedto it.

3. In one page write down the function of plasma proteins.4. Homework delivered will be consisting of 3 documents 1. blood picture, 2.your conclusion, 3. functions of plasma proteins.

5. Deadline for the homework is October 10th 2010. Homework delivered afterthe deadline will be subject to score deductions of up to 50%. Home workscore is 5 points.

6. You can deliver homework at my office or to Dr. Dhalia Morsy Dr. Rana

Rasheed (the clinical pharmacy department TA)7. Please either write in print neatly or use a computer.

8. Useful website:http://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcove

r#v=onepage&q=&f=true
http://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcover


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III. Blood groups & transfusion

ABO system

Rhesus (Rh) system

Blood typing Basis of safe blood transfusion and

donation.

Complications of blood transfusion.


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ABO system

Humans are classified into 4 groups according to thepresence or absence of 2 antigens (agglutingens) on themembrane of their RBCs.

These antigens are either A or B The 4 groups are A (42%),B (9%),AB (3%), and O

(46%). Consequently the plasma of the individual carries one of

2 antibodies (agglutinin) or . For example: an individual that is group A has antibody

in his plasma and an individual that has no antigens(group O) has both antibodies in his plasma.

Blood grouping has an important clinical and forensicsignificance.


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The Rhesus system

Similarly according to the presence orabsence of Rh antigen the humans areclassified into 2 group.

Those that have the Rh factor on the theirRBCs membrane are Rh positive (Rh+)85% while those who dont are called Rhnegative (Rh-) 15%.

Rh factors has also a forensic as well asclinical significance as well.


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Significance of blood grouping

Forensic: paternity test (limited value). DNAtesting is more reliable.

Clinical:1. blood transfusion: Role of thumb when

available always give the identical blood groupto the recipient. If not available the role is tomatch the donor RBCs to the recipientsplasma. According to this role there is a

universal donor which is group O and auniversal recipient which is group AB.2. Marriage and pregnancy of an Rh- women.

Role of anti D.


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Safe blood transfusion anddonation

Donate maximum 3 time a year. Keep good health in general and drink lots of fluids. If you are receiving or supervising a blood transfusion

be sure of the following:

1. Always receive a matched or cross matched blood.What is this?2. In any case the blood should be tested for serological

diseases e.g. Hepatitis B and HIV.3. Only employ credible donors.

4. Monitor the recipient closely for a possible reaction.5. Pay particular attention if the recipient is an Rh-

woman. She should never be given Rh+ blood.6. Watch for safe handling of blood.


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Complications of bloodtransfusion

Donor complications: shock, anaemiawhen does this happen?

Recipients complication

1. Embolism (air or fat)

2. Overloading of the circulation.

3. Blood transmitted diseases e.g. AIDS,Hepatitis

4. Hemolysis


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Hematology overview

Objectives Blood physiology Normal blood picture Blood groups and transfusion Hemostasis (Blood coagulation)

Reticuloendothelial system: lymph nodes and spleen. Pathophysiology of blood diseases:A. Formation (production) disorders1. RBCs disorders: Anaemia, Polycythaemia.

2. WBCs disorders: Leukemia, leukocytosis, &lymphomas3. Platelets disorders: ThrombocytopeniaB. Functional disorders: Bleeding disorders


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Hemostasis

Is the process by which blood loss isprevented and a clot is formed. Bleedingis stopped by 3 independent

mechanisms.

1. Local vasoconstriction.

2. Platelet plug formation.

3. Blood coagulation.


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1. Local vasoconstriction

This occur immediately after the injury and continues for20-30 minutes and some times up to several hours afterthe injury.

This results from contraction of the smooth muscles

within the wall of the blood vessel.

It can be so strong that it results in complete stop ofblood flow through the vessel.

1. The mechanism of vasoconstriction are: 1. Trauma-

activated myogenic mechanism 2. Liberation r localvasoconstrictors e.g. Thromboxane A2 and endothelin.3. Neurogenic mechanism through pain nerve endings.


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2. Platelet plug formation

Due to contact between the platelets and someelement of the vascular wall e.g. collagen.

Platelets swell and becomes more sticky. Theysecrete thromboxane A2 and ADP which in turn

further activate the platelets to become moresticky and so forth. When the rent (tear) of the blood vessel is small

platelet plug can in fact stop the bleeding byitself.

This is another example of a positive feed backloop.


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Platelet plug formation

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3. Blood coagulation

Coagulation factors (1 to 13). They are writtenin Roman numbers e.g. 1 is I, 2 is II. Some ofthem are identified and has names.

Many coagulation factors are proteinssynthesized in the liver and present in theplasma. Also many of them require vitamin Kfor their synthesis. (what is the impact of poor

liver function or vitamin K deficiency onhemostasis?)

(Please refer to the supplementary table ofcoagulation factors provided on my website)


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3. Mechanism of blood coagulation.

1. Formation of prothrombin activator:

A. Intrinsic mechanism. The stimulus is inside theblood. A cascade of activation of coagulation

factors ensues.B. Extrinsic mechanism: due to contact of the

blood with tissue.

For details check your references.

1. Conversion of prothrombin into thrombin.

2. Conversion of fibrinogen into fibrin


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Extrinsic pathway

Factor XII VII

VIIa + tissue factor

X Xa

Prothrombin(II) Thrombin(IIa)

Fibrinogen(I) Fibrin (Ia)XIII a

Cross linked fibrin clot

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Va

Tissue factor

Step requires Ca++ and platelet phospholipid

Common pathway


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Intrinsic pathway

Factor XII XIIa

XI XIa

IX XIaX Xa

Prothrombin(II) Thrombin(IIa)

Fibrinogen(I) Fibrin (Ia)XIII a

Cross linked fibrin clot42

Va

VIIIa

Step requires Ca++ and platelet phospholipid

Common pathway


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Factors that prevent blood coagulation innormal vascular system (in vivo)

1. Vascular factors: smooth endothelium,

negatively charged protein lining of theblood vessels.

2. Anti-thrombin factors.

3. Heparin.p.s. compare and contrast heparin versus

Dicumarol as an anti coagulants.


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Factors that prevent blood coagulationoutside normal vascular system (in vitro)

1. Heparin

2. Ca+ chelating agents e.g. EDTA.

3. Ca+ deionization e.g. citrate

4. Smooth siliconized tubes.


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Reticuloendothelial system (RES)

Anatomy: spleen as well as macrophages of the bonemarrow,, liver, connective tissue and lymph nodes

Function:1. Defense: antibody formation (lymph nodes),

phagocytosis2. Tissue repair: by adding or removing substances e.g.

protein necessary for healing process.3. Blood formation and removal of senile RBCs4. Iron storage

5. The spleen acts as a blood reservoir.6. Lymph nodes filters the blood from bacteria and viruses

and form lymphocytes which in turn forms antibodies


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Home work 1

1. Form a group of your colleagues to be your permanent study group for thiscourse or the semester (maximum 10 per group)

2. Find a blood picture of a relative and check it. Study the blood picture withyour group and write down your findings. Please give me a copy of theblood picture with your finding and conclusion on a separate page attachedto it.

3. In one page write down the function of plasma proteins.4. Homework delivered will be consisting of 3 documents 1. blood picture, 2.

your conclusion, 3. functions of plasma proteins.5. Deadline for the homework is October 10th 2010. Homework delivered after

the deadline will be subject to score deductions of up to 50%. Home workscore is 5 points.

6. You can deliver homework at my office or to Dr. Dhalia Morsy Dr. Rana

Rasheed (the clinical pharmacy department TA)7. Please either write in print neatly or use a computer.

8. Useful website:http://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcove

r#v=onepage&q=&f=true
http://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcoverhttp://books.google.com/books?id=m7X_TPfyCgoC&printsec=frontcover


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Home Work 2

Compare and contrast heparin versusDicumarol as an anti coagulants. Payspecial attention to the mechanism of action

of each drug. Please do it in a table format. Always write

down your reference.

Keep this for your records for pharmacologyclasses (:

This homework is a part of this course.


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Lec.1 Hematology

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