Transcript Tissues Response to Injury

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
‫ﺍﷲ‬
CONCEPT AND
PRINCIPLE
CONCEPT
Concept
of
Complex
thing(complex)
Concept = idea about something (3 types)
concept
situation
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.
flowchart, diagram, equations, models, analogy, etc.
PRINCIPLE
Basis for doing something (by humans)
How to do something (sequence,
steps, guide,rules)
Why do something in a certain way
(logical sequence)
Principle = Basis
Logical relationship between
these 2 basis
How
humans do
something
is logically
based on
his
knowledge
about how
that thing
is related
to what
occur in
Nature
Problemsolving is
based on the
ability to
choose the
right concept
and principle
to use for a
particular
problem.
How something occur (sequence, steps)
Why something occur that way (Nature’s
Law→GOD)
Generator of
Diversity=‫ﺍﷲ‬
Concept
Basis for something occurring (in Nature)
of
principle
Chulan99
‫ﺍﷲ‬
2 Concepts of Disease
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
Agents
(Infectious)
Virus
2
Rickettsiae
Environment
(Non-infectious)
ADVERSE
Hypoxia/Hypoglycaemia
1
INTERACTIONS
Free radical:O2÷,H2O2,OH•
Bacteria
Trauma
Fungi
Protozoan Parasites
3
Temperature extremes
Host
(Inherent)
Atmospheric pressure
Metazoan Parasites
Radiation
Electric shock
Genetic defects
Hormonal imbalance
Electrolyte imbalance
Chemicals/Poisons
+ Inappropriate Immune Response
4
Drugs
Nutritional Imbalance
Hepatic & renal failure
5
Allergy/autoimmunity
LESIONS
(structural abnormalities)
SIGNS
(functional abnormalities)
Clinical Signs/
Symptoms
Alcohol
6
7
Laboratory
Manifestations
+ DEATH
Chulan2003
8
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
1.DEGENERATION
NORMAL
CELL
RESPONSE
TO THE
NECROTIC
TISSUES
2.NECROSIS
MOLECULAR
LESIONS
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
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.
Principles of Classifying Lesions into Groups and Types
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 SUBSTANCE
accumulated & 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 of
LESIONS
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,
Circulatory
disturbances
Abnormalities in the
cardiovascular
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 & chemical
Injury to organs
Abnormalities located in organs that
have undergone anatomical
displacements due to physical injury
Based on the ORGAN & LOCATION
7
Pigmentation
A condition where
there is accumulation
of excess pigments in
the 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 disturbance
without control of
the
body
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
Congenital
anomalies
Abnormalities during
the development of
the
embryo 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 THE
DEVELOPMENTAL 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
‫ﺍﷲ‬
Pathogenesis of Cellular Injury
(cellular injury as reversible or irreversible conditions which occur after the limits of adaptive response to a stimulus are exceeded)
Agents
(Infectious)
Environment
(Non-infectious)
Virus
ADVERSE
Rickettsiae
Hypoxia/Hypoglycaemia
INTERACTIONS
Free radical:O2÷,H2O2,OH•
Bacteria
Trauma
Fungi
Temperature extremes
Host
(Inherent)
Parasites
Atmospheric pressure
Radiation
Electric shock
Genetic defects
Chemicals/Poisons
Hormonal imbalance
+ Inappropriate Immune Response
Electrolyte imbalance
Drugs
Nutritional Imbalance
Hepatic & renal failure
Alcohol
Allergy/autoimmunity
Cell membrane integrity ↓
Oxidative phosphorylation ↓
Aerobic respiration ↓
ATP ↓→Ca++ ↑
ATP ↓
Enzymatic protein synthesis ↓
Phospholipid synthesis ↓
Structural protein synthesis ↓
Phospholipase+Protease+ATPase ↑
Glycolysis ↑ → pH↓ Glycogen↓
DNA integrity ↓
Endonuclease ↑
Protein synthesis ↓
Metabolic derangements ↑
Phospholipid degradation ↑
Na pump ↓→
Ca++
↑ ,H20
↑,K+
↓
Lipid deposition ↑
Phospholipid loss ↑
Lipid peroxidation ↑
LESIONS
(structural abnormalities)
DEGENERATION
(REVERSIBLE)
Histopathology
Membrane damage ↑
NECROSIS
(IRREVERSIBLE)
SIGNS
(functional abnormalities)
Water, fat & glycogen vacuoles
Histopathology
Cellular swelling
Cytoplasmic changes
Cytoplasmic deposition of substances
Nuclear changes
Membrane changes
+ DEATH
Ultrastructural changes
Ultrastructural changes
Cellular swelling
Mitochondrial swelling
Cytoskeletal changes
NECROSIS
Loss of microvilli
Nuclear changes → pyknosis,
Blebs
karyorrhexis, karyolysis
ER swelling
Lysosomes lysis
Myelin figures
INFLAMMATION
Membrane lysis
Nuclear chromatin clumping
Myelin figures
Ribosomal detachment
ER lysis
Intramembranous particle aggregatn
Mitochondrial swelling
Large densities in mitochondria
Autophagy by lysosomes
Chulan2003
Identification of Types of Degeneration
Examine the cytoplasm
under light microscope
with H&E stain
for vacuoles
small size
Presence of
Vacuoles(no colour)
Absence of Vacuoles
presence of aggregates
Examine Size, Shape
and location of Vacuoles
Examine colour, Shape
and location of aggregates
big size
small size
big size
foamy shape rounded shape
fuzzy edge
clear edge
in liver and kidney in liver
Glycogen
Infiltration
Fatty
change
variable sizes
reddish cytoplasm
bluish aggregates
big size
variable sizes
crystal shape rounded shape
clear edge
unclear edge
in foamy cells in liver, kidney, hrt
variable sizes
rounded shape
unclear edge
in adipose tis
Granular
cytoplasm
in liver
reddish
reddish
aggregates
aggregates
in parenchyma. in tunica media
organs
of blood vessels
reddish
aggregates
in capil aries
of organss
in mucous cells
Cholesterol
infiltration
Mucoid
degeneration
Granular
degeneration
Hyaline
degeneration
Amyloid
infiltration
Mucinous
degeneration
Hydropic
degeneration
Fibrinoid
degeneration
Identification of Types of Necrosis
Examine the cell outline
and tissue architecture
of necrotic tissues
Presence of cell outline
and tissue architecture
Absence of cell outline
and tissue architecture
Coagulative necrosis
Examine severity
of loss of details
Examine tissue types
complete loss
fragmentations
muscle
fat
bone
blood vessels
any tissue
at centre
of abscess
at centre
of granuloma
Zenker's
necrosis
Fat
necrosis
osteonecrosis
fibrinoid
necrosis
coagulative
necrosis
Liquefective
necrosis
Caseous
necrosis
with liquefective
necrosis
with bacteria
and leukocytes
Gangrenous
necrosis
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