Pathophysiology PCP 341

Nermien Waly MD, M.Sc., Ph.D. Lecturer School of Pharmacy R2031 ACU nwaly@yahoo.com https://sites.google.com/site/nwaly09/

What is patho-physiology?
it is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome. More formally, it is the branch of medicine which deals with any disturbances of body functions, caused by disease or prodromal symptoms.
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Course objectives (ILOs)

1. Understand the basic biological mechanism(s) of disease processes. 2. Describe the disease manifestation by the way the disease disrupts normal 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 abnormal functions 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 diseased organ(s).
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Why do you (pharmacist to be) study pathophysiology?

Your (Pharmacist) role as a health care professional:

1. Traditional pharmacist skills 2. Patient- oriented (clinical) skills

The role of clinical pharmacist

1. Central clinical pharmacy services

a) b) c) d)

Patient education Drug use evaluation and report In service education Clinical trials
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The role of clinical pharmacist

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 distribution system. 9. Participation in clinical rounds. 10. Crucial health care team member. 11. Role in ICU.

Basic requirements to practice clinical pharmacy

Anatomy and histology Physiology Pathophysiology Pathology Interpretation of common clinical lab results Clinical pharmacology and therapeutics.
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Hematology

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) disorders 1. RBCs disorders: Anaemia, Polycythaemia. 2. WBCs disorders: Leukemia, leukocytosis, & lymphomas 3. Platelets disorders: Thrombocytopenia B. Functional disorders: Bleeding disorders
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Objectives
To gain knowledge of the following: 1. Blood functions 2. Blood groups and principal of blood transfusion. 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 blood 3. 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 is bluish red 2. Specific gravity: 1060 (what is that?) 3. Osmotic pressure: 25-30 mmHg (what is that?) 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 12 this information and if you do not remember it you should look it up. This Information is part of the course and subject to questions in the quizzes and exams.

Functions of the blood

1. Transport medium: oxygen, carbon dioxide, waste products, active substances, 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 fluids and tissues

45% formed elements (hematocrit)

55% plasma

Erythrocytes

91.5% water

Leukocytes

7% proteins

Platelets

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 one 16 of the questions on your first quiz.

Blood cells (formed elements/hematocrit)

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 blood grouping. It is elastic, semi permeable, antigenic character.

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Development of red blood cells

Pluripotent hematopoietic stem 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, blood grouping
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Factors affecting erythropoiesis

1. Oxygen tension of the blood: lowering oxygen tension stimulates erythropoiesis. 2. Erythropoietin 3. 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 storage 6. Hormones e.g. androgens 7. Bone marrow e.g. radiation, aplasia
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2.White blood cells, leukocytes, WBCs

Leukocytes 4000-10,000/microlitre

Granulocytes

Agranulocytes

Neutrophils (PMNs) 40-70%

Monocytes2-10%

Eosimophils 1-6%

Lymphocytes 20-40%

Basophils <1%
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Development of white blood cells

Pluripotent hematopoietic stem cells

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Functions of the white blood cells

Defense /immunity against infection (viral or bacterial), parasite infestation through the following mechanisms: Phagocytosis (neutrophils /monocytes) Antibody formation (lymphocytes) Plays a role in allergic reaction Autoimmune diseases
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1. 2. 3. 4.

3. Blood platelets / thrombocytes

These are granular non-nucleated oval bodies about 2-4 microns in diameter 250,000-500,000/ cubic ml Origin: megakaryocytes in BM Functions: 1. Hemostasis /blood coagulation 2. Phagocytosis 3. Storage and transport
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Development of blood platelets

Pluripotent hematopoietic stem cells

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II. Blood picture

Is a report that shows normal blood parameters. Value: an important diagnostic tool for both blood disorders as well as other diseases. It is important for a health care professional e.g. doctors, pharmacists, nurses etc.. to be able to read and interpret a blood picture.
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Parameters measured in blood picture

Hemoglobin concentration 12-14 gm/dL for women and 14-16 gm/dL for men. MCV (mean corpuscular volume) 80-100 fL MCH (mean corpuscular hemoglobin) 25-32 pg MCHC (mean corpuscular hemoglobin concentration) 31-35 g/Dl RBC count Differential leukocytic count Platelets count Hematocrit value 37-48% ESR, what is it? Its significance?
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Home work
1. Form a group of your colleagues to be your permanent study group for this course or the semester (maximum 10 per group) 2. Find a blood picture of a relative and check it. Study the blood picture with your group and write down your findings. Please give me a copy of the blood picture with your finding and conclusion on a separate page attached to 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 work score 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

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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 the presence or absence of 2 antigens (agglutingens) on the membrane 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 forensic significance.
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The Rhesus system

Similarly according to the presence or absence of Rh antigen the humans are classified into 2 group. Those that have the Rh factor on the their RBCs membrane are Rh positive (Rh+) 85% while those who dont are called Rh negative (Rh-) 15%. Rh factors has also a forensic as well as clinical significance as well.
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Significance of blood grouping

Forensic: paternity test (limited value). DNA testing is more reliable. Clinical: 1. blood transfusion: Role of thumb when available always give the identical blood group to the recipient. If not available the role is to match the donor RBCs to the recipients plasma. According to this role there is a universal donor which is group O and a universal recipient which is group AB. 2. Marriage and pregnancy of an Rh- women. Role of anti D.
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Safe blood transfusion and donation

1. 2. 3. 4. 5. 6. 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: Always receive a matched or cross matched blood. What is this? In any case the blood should be tested for serological diseases e.g. Hepatitis B and HIV. Only employ credible donors. Monitor the recipient closely for a possible reaction. Pay particular attention if the recipient is an Rhwoman. She should never be given Rh+ blood. Watch for safe handling of blood.
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Complications of blood transfusion

1. 2. 3. 4. Donor complications: shock, anaemia when does this happen? Recipients complication Embolism (air or fat) Overloading of the circulation. Blood transmitted diseases e.g. AIDS, Hepatitis 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) disorders 1. RBCs disorders: Anaemia, Polycythaemia. 2. WBCs disorders: Leukemia, leukocytosis, & lymphomas 3. Platelets disorders: Thrombocytopenia B. Functional disorders: Bleeding disorders
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Hemostasis
Is the process by which blood loss is prevented and a clot is formed. Bleeding is 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 for 20-30 minutes and some times up to several hours after the 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 of blood flow through the vessel. 1. The mechanism of vasoconstriction are: 1. Traumaactivated myogenic mechanism 2. Liberation r local vasoconstrictors 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 some element of the vascular wall e.g. collagen. Platelets swell and becomes more sticky. They secrete thromboxane A2 and ADP which in turn further activate the platelets to become more sticky and so forth. When the rent (tear) of the blood vessel is small platelet plug can in fact stop the bleeding by itself. This is another example of a positive feed back loop.
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Platelet plug formation

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3. Blood coagulation
Coagulation factors (1 to 13). They are written in Roman numbers e.g. 1 is I, 2 is II. Some of them are identified and has names. Many coagulation factors are proteins synthesized in the liver and present in the plasma. Also many of them require vitamin K for their synthesis. (what is the impact of poor liver function or vitamin K deficiency on hemostasis?) (Please refer to the supplementary table of coagulation 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 the blood. 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
Tissue factor

VII VIIa + tissue factor

Common pathway

X Xa Prothrombin(II) Thrombin(IIa) Fibrinogen(I) Fibrin (Ia)

Va

XIII a

Cross linked fibrin clot

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Step requires Ca++ and platelet phospholipid

Intrinsic pathway
Factor XII XIIa

XI
IX
Common pathway

XIa
XIa
VIIIa Va

X Xa Prothrombin(II) Thrombin(IIa) Fibrinogen(I) Fibrin (Ia)

XIII a

Cross linked fibrin clot

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Step requires Ca++ and platelet phospholipid

Factors that prevent blood coagulation in normal vascular system (in vivo) 1. Vascular factors: smooth endothelium, negatively charged protein lining of the blood 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 coagulation outside normal vascular system (in vitro)

1. 2. 3. 4.

Heparin Ca+ chelating agents e.g. EDTA. Ca+ deionization e.g. citrate Smooth siliconized tubes.

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Reticuloendothelial system (RES)

1. 2. 3. 4. 5. 6. Anatomy: spleen as well as macrophages of the bone marrow,, liver, connective tissue and lymph nodes Function: Defense: antibody formation (lymph nodes), phagocytosis Tissue repair: by adding or removing substances e.g. protein necessary for healing process. Blood formation and removal of senile RBCs Iron storage The spleen acts as a blood reservoir. 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 this course or the semester (maximum 10 per group) 2. Find a blood picture of a relative and check it. Study the blood picture with your group and write down your findings. Please give me a copy of the blood picture with your finding and conclusion on a separate page attached to 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 work score 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

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Home Work 2
Compare and contrast heparin versus Dicumarol as an anti coagulants. Pay special 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 pharmacology classes (: This homework is a part of this course.
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Have fun studying (:

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