Today’s Quranic verse

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 !







• i. Necrosis

ii.Apoptosis




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 !)







• i. Necrosis

ii.Apoptosis




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 ?


• 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

Today’s Quranic verse

Documents

Transcript of Today’s Quranic verse