Today’s Quranic verse

1. Today’s Quranic verse • In the name of Allah, the Beneficent, the Merciful. • 55.1 The Beneficent God, • 55.2 Taught the Quran. • 55.3 He created man, • 55.4 Taught him the mode of expression. • 55.5 The sun and the moon follow a reckoning. • 55.6 And the herbs and the trees do adore (Him). • 55.7 And the heaven, He raised it high, and He made the balance • 55.8 That you may not be inordinate in respect of the measure. • 55.9 And keep up the balance with equity and do not make the measure deficient. • 55.10 And the earth, He has set it for living creatures; • 55.11 Therein is fruit and palms having sheathed clusters, • 55.12 And the grain with (its) husk and fragrance. • 55.13 Which then of the bounties of your Lord will you deny?

2. INTRO • Today’s Proverb • “You can’t see the forest because of the trees !” • Could anybody see the metaphor here and explain this proverb ? • The metaphor is that the forest is something that you can see clearly if you are above the forest with a bird-view or overview, • whereas if you are right in the middle of the forest amongst the trees, or under the trees then you just can’t see the whole forest because the trees areblocking your view of the whole forest. • To make it worse, nobody tells you that forest=big collection of trees. You have to find out for yourself the hard way.

3. Where is the forest ? I can’t see the forest ! I can only see trees !

4. Now I can see the forest ! • Oh ! Forest is made up of trees ?! • Why didn’t somebody tell me that • in the beginning ?!

5. So…? • Well, I want to be your forest-guide • In the Pathology Forest • To tell you something first • About the forest • The Basic Concepts and Principles • Then about the trees • The Details • So now you know… • If somebody tells you that… • You can’t see the forest because of the trees, it means… • “You can’t see the whole picture of something because you only concentrate on the details !”

6. So…? • What quotation would be useful in this case ? (to overcome the problem of you not seeing the whole picture of something) • “From general to specifics, from simple to complex, from basic to details, from concept to principles, from principles to applications (gs-sc-bd-cp-pa)” • Is this quotation a concept or principle ? • What ???!!! • You are still confused about concept and principle ??? !!!@ #&*

7. Highlights • Concept of concept • Concept of principle • Significance of concept and principle • Concepts of Disease (3) • Cause, Lesions, Signs, Pathogenesis • Why learn Pathology ? • Branches of Pathology (5) • Levels of Knowledge in Pathology (5 levels) • Tissue Response to Injury • Classification of Lesions • Lesion group, lesion types, specific lesions • Course Outline & Summary

8. ﺍﷲ CONCEPT AND PRINCIPLE CONCEPT Concept of concept Complex thing(complex) situation Concept = idea about something (3 types) process Concept =answers the question :what is it ? But Concept > definition > sentences Concept = representation of relationships between ‘things’ (aspects) Formulation of principle by human is based on his concept of the situation or process. Problem-solving is based on the ability to choose the right concept and principle to use for a particular problem. flowchart, diagram, equations, models, analogy, etc. PRINCIPLE Basis for doing something (by humans) How humans do something is logically based on his knowledge about how that thing is related to what occur in Nature How to do something (sequence, steps, guide,rules) Why do something in a certain way (logical sequence) Logical relationship between these 2 basis Principle = Basis How something occur (sequence, steps) Why something occur that way (Nature’s Law→GOD) Generator of Diversity=ﺍﷲ Concept of principle Basis for something occurring (in Nature) Chulan99

9. ﺍﷲ • DISEASE = ( CAUSE → LESIONS → SIGNS ) • MECHANISMS = PATHOGENESIS • CAUSE = Infectious + Non-infectious + Inherent Causes • LESIONS = Structural abnormalities in cells, tissues, organs or systems e.g. enteritis • SIGNS= Functional abnormalities in cells, tissues, organs or systems e.g. diarrhoea • PATHOGENESIS = Mechanisms how the causative agent cause the lesions and the signs in the host • MECHANISMS = 8 Types based on Stage of occurrence in the disease process for Infectious Diseases • Mechanisms of Interactions of factors 5. Mechanisms of Spread in the body • Mechanisms of Entry into host 6. Mechanisms of Lesion development • Mechanisms of Infection of tissues 7. Mechanisms of Signs development • Mechanisms of Inappropriate Immune Response 8. Mechanisms of Death 2 Concepts of Disease Agents (Infectious) Environment (Non-infectious) Virus Rickettsiae Bacteria Fungi Protozoan Parasites Metazoan Parasites ADVERSE INTERACTIONS 2 1 Hypoxia/Hypoglycaemia Free radical:O2÷,H2O2,OH• Trauma Temperature extremes Atmospheric pressure Radiation Electric shock Chemicals/Poisons Drugs Nutritional Imbalance Alcohol Host (Inherent) 3 Genetic defects Hormonal imbalance Electrolyte imbalance Hepatic & renal failure Allergy/autoimmunity + Inappropriate Immune Response 4 5 LESIONS (structural abnormalities) 6 SIGNS (functional abnormalities) 7 Clinical Signs/ Symptoms Laboratory Manifestations + DEATH 8 Chulan2003

10. Cell Injury • The first topic for today is… • Cell Injury • But before we talk about Cell Injury, let us talk about… • Something more basic…

11. Cell Injury • What is General Pathology ? (compared to Systemic Pathology ?) • What is the basic unit of structure in the body that form the basis for explaining disease processes in General Pathology ? • What is your concept of ‘disease’ ? (3 concepts) • Is disease ‘abnormalities’ or ‘injuries’ ? (or both ?) • What is your concept of Cell Injury? (based on your knowledge of ‘cell’ and ‘injury’ ?) • What is the significance of this concept in Pathology? (useful for what ?) • What are the other related concepts in Pathology ? • Concept of CI – the structural abnormalities in the cell including the organelles or cytoskeleton • Form the basis for explaining disease processes • 5 main groups of cellular response to injury (Robbins) • Related terms – Tissue Response to Injury = 10 groups of lesions (Smith)

12. CELLULAR RESPONSES TO INJURY • Table 1-1. CELLULAR RESPONSES TO INJURY • Cellular Adaptations • Atrophy, hypertrophy, hyperplasia, metaplasia • Acute Cell Injury • Reversible Injury • Cell death (Irreversible Injury) • Necrosis Apoptosis • Subcellular Alterations and Cell Inclusions • Intracellular Accumulations • Pathologic Calcification • Cellular Adaptations = Growth Disturbances • Reversible and irreversible cell injury leading to necrosis or apoptosis-are morphologic patterns of acute cell injury induced by various stimuli. • subcellular alterations – in cell orgenelles and cytoskeleton, which occur largely as a response to more chronic or persistent injurious stimuli; • intracellular accumulations of a number of substances-lipids, carbohydrates, and proteins - which occur as a result of derangements in cell metabolism or excessive storage; • and pathologic calcification, a common consequence of cell and tissue injury.

13. What are the cellular responses to injury ? • 5 main groups of responses (based on Robbins) • 1. Cellular Adaptations • 2. Acute Cell Injury • a.Reversible Injury • b. Cell death (Irreversible Injury) • i. Necrosis ii.Apoptosis • 3. Subcellular Alterations and Cell Inclusions • 4. Intracellular Accumulations • 5. Pathologic Calcification

14. Evaluate this statement • One of the cellular responses to injury is Acute Cell Injury ! • What is wrong with this statement ? • The word ‘Injury’ is wrongly used !

15. What are the cellular responses to injury ? • 5 main groups of responses (based on Robbins) • 1. Cellular Adaptations • 2. Acute Cell Injury • a.Reversible Injury • b. Cell death (Irreversible Injury) • i. Necrosis ii.Apoptosis • 3. Subcellular Alterations and Cell Inclusions • 4. Intracellular Accumulations • 5. Pathologic Calcification

16. Confusing ! • It is a bit confusing to use the same word ‘injury’ (as in Acute Cell Injury) to name the response to it (to injury) ! • It is like answering the question: “What is the response of a cell to a stimulus ?” and you replied “Stimulus” !!!??? • Lets try it again… • What is one of the cellular response to injury ? • Acute cell injury • If you delete the word ‘acute’ and ‘cell’ from your answer (because these words are redundant) you are left with the word ‘injury’ ! • So, it is like saying ‘one of the cellular responses to injury is injury ! (Not logical !)

17. What are the cellular responses to injury ? • 5 main groups of responses (based on Robbins) • 1. Cellular Adaptations • 2. Acute Cell Injury • a.Reversible Injury • b. Cell death (Irreversible Injury) • i. Necrosis ii.Apoptosis • 3. Subcellular Alterations and Cell Inclusions • 4. Intracellular Accumulations • 5. Pathologic Calcification

18. Evaluate this statement One of the cellular responses to injury is Acute Cell Injury which can be classified to Reversible Injury and Irreversible Injury. • What is wrong with this statement ? • It is confusing to state that the cellular responses to injury include “Reversible Injury” and Irreversible Injury”

19. Need • There is a need to define ‘Injury’ clearly and there is a need to use different terms to name the responses to the injury ! • What is your concept of ‘Injury’ ? • Robbins did not define Injury clearly ! • Smith defined injury as ‘Biochemical lesions’ • When a stimulus is applied to a cell, it may result in Biochemical Lesions • The cellular response is the response of the cell to the Biochemical Lesions in order to get back to normal ! (Homeostasis) • Robbins defined Cell Injury as… • “reversible or irreversible conditions which occur after the limits of adaptive response to a stimulus are exceeded” • Which require that the term “adaptive response” to be defined before the term “cell injury” could be clearly understood ! • The Adaptive Response of Robbins = Growth Disturbances of Smith ! • The concept of Cell Injury of Robbins may not be accurate or applicable in all cases because it presumes that Cell injury can only occur AFTER the Adaptive Responses had occurred ! • Irreversible Cell Injury (Degeneration) can occur without Growth Disturbances !

20. Evaluate these ! • Is ‘Inflammation’ included under Cell Injury ? • Is ‘Thrombosis’ included under Cell Injury ? • Is ‘Neoplasia’ included under Cell Injury ? • Why is Inflammation, Thrombosis and Neoplasia not included under Cell Injury ? • Because according to Robbins, Cell injury are limited to the responses of the Cell only, not tissues or organs or systems of the body ! • Should the responses be limited to cells only or should be more comprehensive (as in tissues) ? • There is a need for more useful concepts that will make the knowledge on pathology clearer. • Which concept is more useful: ‘Cell Injury’ or ‘Tissue Response to Injury’ in General Pathology ?

21. So ?! • Which concept is more useful: ‘Cell Injury’ or ‘Tissue Response to Injury’ in General Pathology ? • The concept of Cell Injury of Robbins is a bit confusing because: • It uses the same word ‘Injury’ to denote one of the responses to Injury • It uses the term ‘Acute Cell Injury’ • It uses the term ‘Reversible Injury’ and ‘Irreversible Injury’ under ‘Acute Cell Injury’ • On the hand, the concept of ‘Tissue Response to Injury’ of Smith is clearer and more useful because: • ‘Tissue Response to Injury’ is the most basic concept in General Pathology which differentiate General Pathology from Systemic Pathology • Tissue Response to Injury = Lesions (COL) which refers to ‘Structural Abnormalities’ of which there are 10 groups including Inflammation, Thrombosis and Neoplasia. • ‘Tissue Response to Injury’ Concept include the concept of Degeneration and Necrosis for Reversible and Irreversible Injury respectively! • You as students of Pathology should appreciate the usefulness of any concept used in Pathology as they are used in the text books. • The concept of Cell Injury of Robbins has limitations, but the Knowledge of Pathology on Cell Injury is used in our discussion because Robbins text book has all the details for your reference!

22. So, what happened to Robbins classification of cellular responses compared to Smith ? • 5 main groups of responses (based on Robbins) • 1. Cellular Adaptations = Growth Disturbances • 2. Acute Cell Injury = Degeneration + Necrosis + Apoptosis • a.Reversible Injury=Degeneration • b. Cell death (Irreversible Injury) • i. Necrosis = Necrosis ii.Apoptosis = Apoptosis • 3. Subcellular Alterations and Cell Inclusions = Degeneration (Mechanisms) • 4. Intracellular Accumulations = Degeneration + Pigmentation • 5. Pathologic Calcification = Miscellaneous Conditions

23. STIMULUS 1.DEGENERATION 2.NECROSIS NORMAL CELL MOLECULAR LESIONS Tissue Response to Injury(Histopathological Concept) RESPONSE TO THE NECROTIC TISSUES 9.PIGMENTATION NECROSIS 3.INFLAMMATION=COMPLEX SETS OF TISSUE RESPONSE TO INJURY AT SITE OF INJURY =D+N+CD+GD+IIC 4.CD=D OF CVS 5.GD=CHANGE IN NUMBER, SIZE, TYPE AND ARRANGEMENT IIC=INCREASED INFLAMMATORY CELLS GD→DYSPLASIA→6..NEOPLASIA GD→FOETAL STAGE →7.CONGENITAL ANOMALIES CHEMICAL+PHYSICAL STIMULI →8.TRAUMA PIGMENTS→9.PIGMENTATION OTHERWISE 10.MISCELLANEOUS

24. Principles for Classifying Lesions into 10 groups: • The 10 LG are classified based on location, appearance and time of occurrence of the lesion (LAT) PDN GCI NCT M or PD NG CI NC TM (Places) • If it occur in the cell cytoplasm with the presence of coloured substances (pigments) without staining, then it is Pigmentation. • If it occur in the cell cytoplasm without pigments, then it is Degeneration. • If it occur in the cytoplasm, and nucleus and cell membrane, then it is Necrosis. • If it involve changes in cell number, size, type and arrangement, then it is Growth Disturbances (GD). • If it involves abnormalities in the Circulatory System (CS), then it is Circulatory Disturbances (CD). (CS=Heart+Blood vessels+Blood) • If it involve increase number of inflammatory cells in the injured tissues with degeneration, necrosis, GD and CD, then it is Inflammation. • If it involve growth disturbances with anaplastic features, then it is Neoplasia. • If it involve growth and developmental disturbances during the foetal stage, then it is Congenital Anomalies. • If it involve anatomical displacement of organs or strutures, then it is Trauma. • If it is not in the other 9 groups, then it is Miscellaneous.

25. Concepts and Principles of Classification of Lesions Principles of Classifying Lesions into Groups and Types

27. ﺍﷲ Pathogenesis of Cellular Injury(cellular injury as reversible or irreversible conditions which occur after the limits of adaptiveresponse to a stimulus are exceeded) Agents (Infectious) Environment (Non-infectious) Virus Rickettsiae Bacteria Fungi Parasites ADVERSE INTERACTIONS Hypoxia/Hypoglycaemia Free radical:O2÷,H2O2,OH• Trauma Temperature extremes Atmospheric pressure Radiation Electric shock Chemicals/Poisons Drugs Nutritional Imbalance Alcohol Host (Inherent) Genetic defects Hormonal imbalance Electrolyte imbalance Hepatic & renal failure Allergy/autoimmunity + Inappropriate Immune Response Cell membrane integrity ↓ Aerobic respiration ↓ Enzymatic protein synthesis ↓ Structural protein synthesis ↓ DNA integrity ↓ Metabolic derangements ↑ Oxidative phosphorylation ↓ ATP ↓ Na pump ↓→ Ca++ ↑ ,H20 ↑,K+ ↓ Glycolysis ↑ → pH↓ Glycogen↓ Protein synthesis ↓ Lipid deposition ↑ ATP ↓→Ca++ ↑ Phospholipid synthesis ↓ Phospholipase+Protease+ATPase↑ Endonuclease ↑ Phospholipid degradation ↑ Phospholipid loss ↑ Lipid peroxidation↑ Membrane damage↑ LESIONS (structural abnormalities) DEGENERATION (REVERSIBLE) NECROSIS (IRREVERSIBLE) SIGNS (functional abnormalities) Histopathology Water, fat & glycogen vacuoles Cellular swelling Cytoplasmic deposition of substances Histopathology Cytoplasmic changes Nuclear changes Membrane changes + DEATH Ultrastructural changes Cellular swelling Mitochondrial swelling Loss of microvilli Blebs ER swelling Myelin figures Nuclear chromatin clumping Ribosomal detachment Intramembranous particle aggregatn Autophagy by lysosomes Ultrastructural changes Cytoskeletal changes Nuclear changes → pyknosis, karyorrhexis, karyolysis Lysosomes lysis Membrane lysis Myelin figures ER lysis Mitochondrial swelling Large densities in mitochondria NECROSIS INFLAMMATION Chulan2003

28. Identification of Types of Degeneration

29. Identification of Types of Necrosis

30. Normal cell Blebs Clumping of nuclear chromatin Autophagy by Lysosomes Aggregation of intramembranous particles ER swelling Dispersion of ribosomes Mitochondrial swelling Small densities Myelin figures Lysis of ER Mitochondrial swelling Large densities