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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). - PowerPoint PPT Presentation
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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?
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 are blocking 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.
Where is the forest ?I can’t see the forest !I can only see trees !
•Now I can see the forest !•Oh ! Forest is made up of trees ?!•Why didn’t somebody tell me that •in the beginning ?!
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 !”
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 ??? !!!@ #&*
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
Concept = idea about something (3 types)
Complex thing(complex)
situation
process
Concept =answers the question :what is it ? But Concept > definition > sentences
Concept = representation of relationships between ‘things’ (aspects)
flowchart, diagram, equations, models, analogy, etc.
Principle = Basis
Basis for doing something (by humans)
Basis for something occurring (in Nature)
How to do something (sequence, steps, guide,rules)
Why do something in a certain way (logical sequence)
How something occur (sequence, steps)
Why something occur that way (Nature’s Law→GOD)
Logical relationship between these 2 basis
CONCEPT
PRINCIPLE
How humans do something is logically based on his knowledge about how that thing is related to what occur in Nature
Generator of
Diversity=اهللا
Chulan99
CONCEPT AND PRINCIPLE
Concept
of
concept
Concept
of
principle
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.
اهللا
2 Concepts of Disease
Environment(Non-infectious)
LESIONS(structural abnormalities)
Agents(Infectious)
Host(Inherent)
Clinical Signs/Symptoms
+ Inappropriate Immune Response
Chulan2003
Virus
Rickettsiae
Bacteria
Fungi
Protozoan Parasites
Metazoan Parasites
Genetic defects
Hormonal imbalance
Electrolyte imbalance
Hepatic & renal failure
Allergy/autoimmunity
+ DEATH
Hypoxia/Hypoglycaemia
Free radical:O2÷,H2O2,OH•
Trauma
Temperature extremes
Atmospheric pressure
Radiation
Electric shock
Chemicals/Poisons
Drugs
Nutritional Imbalance
Alcohol
ADVERSE
INTERACTIONS
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
1. Mechanisms of Interactions of factors 5. Mechanisms of Spread in the body
2. Mechanisms of Entry into host 6. Mechanisms of Lesion development
3. Mechanisms of Infection of tissues 7. Mechanisms of Signs development
4. Mechanisms of Inappropriate Immune Response 8. Mechanisms of Death
LaboratoryManifestations
SIGNS(functional abnormalities)
8
12
3
4
5
6
7
اهللا
Cell Injury
• The first topic for today is…
• Cell Injury
• But before we talk about Cell Injury, let us talk about…
• Something more basic…
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)
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.
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
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 !
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
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 !)
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
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”
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 !
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 ?
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!
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
Tissue Response to Injury(Histopathological Concept)
STIMULUS
NORMALCELL
MOLECULARLESIONS
1.DEGENERATION 2.NECROSIS
NECROSIS
RESPONSETO THENECROTICTISSUES 3.INFLAMMATION=COMPLEX
SETS OF TISSUE RESPONSETO INJURY AT SITE OF INJURY=D+N+CD+GD+IIC
4.CD=D OF CVS
5.GD=CHANGE IN NUMBER, SIZE, TYPE AND ARRANGEMENTIIC=INCREASED INFLAMMATORY CELLS
GD→DYSPLASIA→6..NEOPLASIAGD→FOETAL STAGE →7.CONGENITAL
ANOMALIES
CHEMICAL+PHYSICAL STIMULI →8.TRAUMAPIGMENTS→9.PIGMENTATION
OTHERWISE 10.MISCELLANEOUS
9.PIGMENTATION
Principles for Classifying Lesions into 10 groups:
1. 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)
2. If it occur in the cell cytoplasm with the presence of coloured substances (pigments) without staining, then it is Pigmentation.
3. If it occur in the cell cytoplasm without pigments, then it is Degeneration.
4. If it occur in the cytoplasm, and nucleus and cell membrane, then it is Necrosis.
5. If it involve changes in cell number, size, type and arrangement, then it is Growth Disturbances (GD).
6. If it involves abnormalities in the Circulatory System (CS), then it is Circulatory Disturbances (CD). (CS=Heart+Blood vessels+Blood)
7. If it involve increase number of inflammatory cells in the injured tissues with degeneration, necrosis, GD and CD, then it is Inflammation.
8. If it involve growth disturbances with anaplastic features, then it is Neoplasia.
9. If it involve growth and developmental disturbances during the foetal stage, then it is Congenital Anomalies.
10. If it involve anatomical displacement of organs or strutures, then it is Trauma.
11. If it is not in the other 9 groups, then it is Miscellaneous.
Lesion groups Concept Principles of classification into groups
Principles of classification into types
1 Degeneration Non-pigmented cytoplasmic changes
Abnormalities located in the cytoplasm with accumulation of non-pigmented endogenous substances
Based on the type of SUBSTANCEaccumulated & on the TYPE of cell
2 Necrosis Cytoplasmic, nuclear and membrane changes
Abnormalities located in the nucleus, cytoplasm & cell membrane
Based on GROSS APPEARANCE of the tissue & the STRUCTURE of the cell
3 Inflammation A complex sets of tissue response to injury involving neural, vascular, humoral & cellular reaction within the site of injury
Complex abnormalities involving degeneration, necrosis, growth disturbances, circulatory disturbances and increase of inflammatory cells in tissues
Based on EXUDATES & type ofLESIONS
4 Growth Disturbances
Abnormal cell growth but still under control of the body
Abnormalities of cell growth affecting the whole cell in terms of size, number, type and arrangement of cells in tissues
Based on the SIZE , NUMBER ,TYPE & ARRANGEMENT of cells,
Circulatorydisturbances
Abnormalities in thecardiovascular system (CVS)
Abnormalities located in the CVS i.e. in the blood, heart & vessels (which can effect on other tissue (e.g. liver, lung)
Based on the ORGAN, TISSUE & VESSEL
6 Trauma Physical & chemicalInjury to organs
Abnormalities located in organs that have undergone anatomical displacements due to physical injury
Based on the ORGAN & LOCATION
7 Pigmentation A condition wherethere is accumulationof excess pigments inthe cells
Abnormalities located in the cytoplasm with accumulation of pigmented substances of endogenous or exogenous origin
Based on the type of EXOGENOUS &ENDOGENOUS PIGMENTS, HEPATOGENOUS or HAEMATOGENOUS
8 Neoplasia Growth disturbancewithout control of thebody
Abnormalities of cell growth affecting the whole cell in terms of size, number, type and arrangement of cells in tissues, but with anaplastic features
Based on HISTOGENESIS (where the tumor come from) & its BEHAVIOUR (benign or malignant)
9 Congenitalanomalies
Abnormalities duringthe development of theembryo or foetus
Abnormalities of cell growth affecting the whole cell, in terms of size, number, type and arrangement of cells in tissues, but occurring during the development of the embryo or foetus
Based on the FAILURE OF THEDEVELOPMENTAL PROCESS (e.g. failure of organ to close, separate, persisting structures, abnormal location & enzyme defects
10 Miscellaneous Miscellaneous conditions not in the other groups
Abnormalities that are excluded from the other groups
Based mainly on location
Principles of Classifying Lesions into Groups and Types
Pathogenesis of Cellular Injury(cellular injury as reversible or irreversible conditions which occur after the limits of adaptive response to a stimulus are exceeded)
Environment(Non-infectious)
LESIONS(structural abnormalities)
Agents(Infectious)
Host(Inherent)
NECROSIS(IRREVERSIBLE)
SIGNS(functional abnormalities)
+ Inappropriate Immune Response
Chulan2003
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
Virus
Rickettsiae
Bacteria
Fungi
Parasites
Genetic defects
Hormonal imbalance
Electrolyte imbalance
Hepatic & renal failure
Allergy/autoimmunity
+ DEATH
DEGENERATION(REVERSIBLE)
Hypoxia/Hypoglycaemia
Free radical:O2÷,H2O2,OH•
Trauma
Temperature extremes
Atmospheric pressure
Radiation
Electric shock
Chemicals/Poisons
Drugs
Nutritional Imbalance
AlcoholCell membrane integrity ↓
Aerobic respiration ↓
Enzymatic protein synthesis ↓
Structural protein synthesis ↓
DNA integrity ↓
Metabolic derangements ↑
INFLAMMATION
ATP ↓→Ca++ ↑
Phospholipid synthesis ↓
Phospholipase+Protease+ATPase ↑
Endonuclease ↑
Phospholipid degradation ↑
Phospholipid loss ↑
Lipid peroxidation ↑
Membrane damage ↑
Oxidative phosphorylation ↓
ATP ↓
Na pump ↓→ Ca++ ↑ ,H20 ↑,K+ ↓
Glycolysis ↑ → pH↓ Glycogen↓
Protein synthesis ↓
Lipid deposition ↑
ADVERSE
INTERACTIONS
Ultrastructural changes
Cytoskeletal changes
Nuclear changes → pyknosis,
karyorrhexis, karyolysis
Lysosomes lysis
Membrane lysis
Myelin figures
ER lysis
Mitochondrial swelling
Large densities in mitochondria
Histopathology
Cytoplasmic changes
Nuclear changes
Membrane changes
اهللا
Histopathology
Water, fat & glycogen vacuoles
Cellular swelling
Cytoplasmic deposition of substances
NECROSIS
Identification of Types of Degeneration
G lycog enIn filtra t ion
sm all s izefoam y sh ap efu zzy ed g e
in live r an d k id n ey
sm all s ize
F attych an g e
b ig s izerou n d ed sh ap e
c lear ed g ein live r
C h o les te ro lin filtra tion
b ig s izec rys ta l sh ap e
c lear ed g ein foam y ce lls
b ig s ize
H yd rop icd eg en era tion
variab le s izesrou n d ed sh ap e
u n c lear ed g ein live r, k id n ey, h rt
M u co idd eg en era tion
variab le s izesrou n d ed sh ap e
u n c lear ed g ein ad ip ose t is
va riab le s izes
E xam in e S ize , S h ap ean d loca tion o f V acu o les
P resen ce o fV acu o les (n o co lou r)
G ran u la rd eg en era tion
G ran u la rcytop lasm
in live r
H ya lin ed eg en era tion
red d ishag g reg a tes
in p aren ch ym a.org an s
F ib rin o idd eg en era tion
red d ishag g reg a tes
in tu n ica m ed iao f b lood vesse ls
A m ylo idin filtra tion
red d ishag g reg a tesin cap illa rieso f o rg an ss
red d ish cytop lasm
M u c in ou sd eg en era tion
in m u cou s ce lls
b lu ish ag g reg a tes
E xam in e co lou r, S h ap ean d loca tion o f ag g reg a tes
A b sen ce o f V acu o lesp resen ce o f ag g reg a tes
E xam in e th e cytop lasmu n d er lig h t m ic roscop e
w ith H & E s ta info r vacu o les
Identification of Types of Necrosis
Z en ker'sn ec ros is
m u sc le
F a tn ec ros is
fa t
os teo -n ec ros is
b on e
fib rin o idn ec ros is
b lood vesse ls
G an g ren ou sn ec ros is
w ith b ac te riaan d leu kocytes
w ith liq u e fec tiven ec ros is
coag u la tiven ec ros is
an y t is su e
E xam in e t is su e typ es
C oag u la tive n ec ros is
P resen ce o f ce ll ou tlin e an d t is su e a rch itec tu re
L iq u e fec tiven ec ros is
a t cen treo f ab scess
com p le te loss
C as eou sn ec ros is
a t cen treo f g ran u lom a
frag m en ta tion s
E xam in e severityo f loss o f d e ta ils
A b s en ce o f ce ll ou tlin ean d t is s u e a rch itec tu re
E xam in e th e ce ll ou tlin ean d t is s u e a rch itec tu re
o f n ec ro tic t is su es
BlebsClumping of nuclear chromatinAutophagy by LysosomesAggregation of intramembranous particlesER swellingDispersion of ribosomesMitochondrial swellingSmall densitiesMyelin figuresLysis of ERMitochondrial swellingLarge densities
Normal cell