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Basic Principles Of Cell Injury And
Adaptation
Dr. Satheesh S,Pharm.D.,
Associate Professor
Department of Pharmacy Practice
Contents
Contents
● Introduction
● Definitions
● Homeostasis
● Types of Feedback System
● Cell Injury
● Causes of Cell Injury
Introduction
Introduction
● Pathophysiology is the study of biological and physical manifestations of
diseases as the correlate with the underlying abnormalities and
physiological disturbances
● Pathophysiology does not dealing with the treatment of diseases
● Instead it explains about the process within the body and it’s sign and
symptoms
● It’s a advanced field of study beyond anatomy and physiology
● It’s concerned with the study of disease, infections, illness, and dysfunctions
in the human body
Definition
Definitions
Disease:
● The term Disease refers to any conditions that impairs normal function
● I.e: Functional Abnormality
● It may be cause by external factors such as infectious disease or
● It may be cause by internal factors such as autoimmune disease.
Disorder:
● Anatomical abnormalities or disturbances are known as disorder
● Like Fracture, Alzheimer and Diabetes, etc.,
● Disorders are mainly categories into Mental disorder, Physical disorder, Genetic
disorder, Emotional and Behaviour disorder and Functional disorder.
Definitions
Inflammation:
● It is a protective mechanism of the body to remove the injuries or stimuli or
complex biological response of vascular tissue against the harmful stimuli
like pathogen, damaged cells or irritants.
● Inflammation is not the synonyms of infection. But sometimes inflammation
is caused by the infections
Infection:
● Infection means the growth of parasitic organism within the body expect
the normal growth of the usual bacterial flora in the intestinal tract
Definitions
Immunity:
● It is the defense mechanism to avoid the infection, disease or other
unwanted biological invasion
Homeostasis
Homeostasis
● Ability to maintain relatively stable internal conditions despite a changing
external environment.
● Dynamic state of equilibrium or balance
● Body is said to be in homeostasis when it's cellular needs are adequately met
and functional activities are occurring smoothly
● Virtually every organ system plays a role in maintaining the internal
environment
● Homeostasis regulatory mechanism consist of 5 parts
Homeostasis
● Ability to maintain relatively stable internal conditions despite a changing
external environment.
● Dynamic state of equilibrium or balance
● Body is said to be in homeostasis when it's cellular needs are adequately met
and functional activities are occurring smoothly
● Virtually every organ system plays a role in maintaining the internal
environment
● Homeostasis regulatory mechanism consist of 5 parts
Homeostasis Regulatory Mechanism
Effectors
05
● Effectors are the cell or organ
● That responds according to the command of the control
center via motor receptor
Motor Receptor
04
● It send the reply coming from integrated center to
effector
Integrated Center
03
● It analyze the incoming message and send the reply via
motor receptor (Brain and Spinal Cord)
Sensory Neurons
02
● It receives information from receptor and sends input
messages to integrated center
Receptors
01
● It responds to a stimulus
● It monitors the change in control condition and send the
input information to control center/ Integrated center via
sensory receptors
Types of Feedback
System
Types of Feedback System
Types of Feedback System
Negative
Positive
Negative Feedback System
When the response of effectors opposes the original stimulus, it is called Negative
Feedback because its neglect the stimulus
An example for the negative feedback system is thermostat in home
Temperature sensors turn on and off to maintain the air temperature within a
specific range, condition range
In the same way our body homeostasis mechanism control our body temperature
Negative Feedback System
● Some stimulus (Stress) disrupts homeostasis (Control Condition) by an
increasing in body temperature
● Due to this thermoreceptors (Temperature sensitive receptors) in the skin and
brain activate and send input message through nerve impulse to the control
center
● Control center analyze the input message and send output message to effectors
(Skin).
Negative Feedback System
● Effectors according to output message of control center increases sweating from
sweat glands causes increased heat loss by evaporation
● Finally, decreases the temperature in the form of response and normalize the
body temperature (Control Condition)
Positive Feedback System
The effectors add to the initial stimulus instead of negativen it, speeding up the
process.
● Labor contraction is the best example for the Positive Feedback System
● Labor contraction force baby’s head or body into birth canal
● It produces effect on control condition and increase distension of cervix of
uterus
● It activates the stretch receptors of the cervix and send input messages to the
control center through sensory nerve impulse
Positive Feedback System
● Control center activates the hypothalamus and pituitary gland and send the
output message to increase oxytocin secretion in blood
● Oxytocin produces their effect on to the effector (cervix of uterus) and cause
distension of cervix of uterus than the normal value to push the baby further
into birth canal
● Birth of baby decreases distension of cervix of uterus and interrupts Positive
Feedback Cycle
Cell Injury
Cell Injury
● Cell injury occurs as a results of Physical, Chemical or Biological insults or as
results of vital substrate deficiency
● The term cell injury is used to indicate a state in which the capacity for
physiological adaptation is exceeded.
● This may occur when the stimulus is excessive or when the cell is no longer
capable to adapt without suffering some form of damage.
Cell Injury
● The capacity for adaptation and the sensitivity to different types of injury varies
according to cell type (i.e: Myocardial Cells and Neurons are highly sensitive to
ischemic injury)
● Cell injury may be Reversible (Non-lethal damage which generally can be
corrected by removal of stimulus) or Irreversible (Lethal damage)
● Genetic defect, abnormalities of several dietary factors, immune reaction,
physical or chemical agent may cause the cell injury
● Commonly Ischemia and Hypoxia are the two forms of cell injury
Reversible Cell Injury
If the hypoxic or ischemic effect is for short duration then it produce reversible cell
injury because this kind of effect is restore by the vascular circulation.
Example:
● Coronary artery occlusion and
● Myocardial contractility, etc.,
Reversible Cell Injury
Some of the sequential biochemical and ultrastructural changes in reversible cell
injury as follows
1. Depletion of ATP
2. Intracellular lactic acidosis and nuclear clumping
3. Effect on plasma membrane
a. Failure of Na+ - K+ ATPase pump
b. Failure of Ca++ pump
4. Decrease Protein Synthesis
1. Depletion of ATP
● ATP is the primary requirement for synthesis of protein, lipid and cell
membrane, etc.,
● In human body ATP is produced by aerobic and anaerobic process.
● Aerobic is carried out by the mitochondria whereas anaerobic carried out by
glucose/glycogen
● In the ischemic condition, supply of oxygen and glucose both are get affected
● So decrease in the production of ATP results in fail in the production of
protein, lipid and cell membrane, etc., leads to cell injury
1. Depletion of ATP
● In hypoxia, due to lack of oxygen supply there will be a formation of demand
● This may due to RBC disorder, Heart disease, Lung disease will form
● Generally anaerobic cell injury are less when compared with aerobic
2. Intracellular lactic acidosis and nuclear clumping
● Due to low oxygen supply aerobic ATP formation process get affected and
mitochondria fails to work
● So anaerobic glycolytic pathway start to produce ATP
● This results in rapid depletion of glycogen and accumulate lactic acid
● It lower the intracellular pH due to intracellular acidosis and produce
clumping of nuclear chromatin
● This effect release the lysosomes and it produce cellular digestion
3. Effect on plasma membrane
● Plasma membrane required phospholipid for continuous repair but due to
lack of ATP fatty acid not form the phospholipids
● Due to this effect plasma membrane pumps get affected and the regulation
of calcium, sodium and potassium get affected
a. Failure of Na+ - K+ ATPase pump
b. Failure of Ca++ pump
a. Failure of Na+ - K+ ATPase pump
● Na+ - K+ ATPase pump is useful for the exchange of Na+ inside to outside and K+
outside to inside from the cell
● Lower ATP affect the activity of this pump and Na+ get accumulate inside the cell
and K+ outside of the cell
● Accumulation of Na+ inside the cell retain the water and increase intracellular
water level and hydrophobic swelling occur due to disruption in osmotic
pressure
b. Failure of Ca++ pump
● Accumulation of Na+ inside the cell produce affect in the intracellular level of
Ca++
● Excess Ca++ accumulate inside the cell as well as into the mitochondria leads
to reversible cell damage
4. Decrease Protein Synthesis
● Lack of oxygen effect disturb the intracellular osmotic balance of the cell
● So endoplasmic reticulum and golgi apparatus swell up
● So the ribosome detach from the granular endoplasmic reticulum and it get
inactive
● This effect decreases the synthesis of protein
Irreversible Cell Injury
● Long lasting/persistence ischemic or hypoxic effect produce cell death or
irreversible damage.
● If cells fails to reverse mitochondrial function as well as disturbance in cell
membrane/ plasma membrane function cause irreversible cell injury
It’s of two types
I. Ca+ influx produce excitotoxicity into the cell
a. Effect of activated phospholipase
b. Effect of activated protease
c. Effect of activated endonuclease
II. Low pH of cell activate and release the lysosomal hydrolytic enzyme
I. Ca+ influx produce excitotoxicity into the cell
Large amount of intracellular Ca++ produce damage in mitochondrial cell wall as well
as excitotoxicity (Activation of number of enzymes like phospholipase, endonuclease
and protease, etc.,)
This effect damage the cell structure such as component of cytoskeleton, plasma
membrane and DNA etc.,
a. Effect of activated phospholipase
● Activated phospholipase degrade the membrane phospholipids which is the
main constituents of plasma membrane.
● As well as due to lack of ATP generation new phospholipid will not form and it
aggregate the effects.
b. Effect of activated protease
● Activated protease damage the cytoskeleton of the cell membrane leads to
irreversible cell injury
c. Effect of activated endonuclease
● Activated endonuclease damages the nucleoprotein as per below process
○ Condense or clumps the nucleus
○ Produce fragments of nucleus
○ Dissolve the nucleus
II. Low pH of cell activate and release the
lysosomal hydrolytic enzyme
● Lack of oxygen decrease the intracellular pH and it activate or release the
lysosomal hydrolytic enzyme like Lactic Dehydrogenase (LDH), Creatinine
Kinase (CK), hydrolyse RNAse, DNAse, Glycosidase, Phosphatase, Lipase,
Amylase, Cathepsin, Etc.,
● Activation of this enzyme digest the cellular components through the phagocytic
effects and cause the irreversible cell injury.
Causes of Cell Injury
Causes of Cell Injury
Types:
1. Genetic - Gene defects, Chromosomal Abnormalities
2. Nutritional - Deficiency or excess of dietary substance, e.g - Iron, Vitamins
3. Immune - Immune system works for foreign agents in some cases it will
destroy the own cell . Example: a. Anaphylactic Reaction b. Autoimmune
4. Endocrine - Deficient or excessive hormone activity
5. Physical Agents - Mechanical trauma, Thermal damage, Irritation (UV and
Ionizing)
Causes of Cell Injury
Types:
6. Chemical Agents - The chemicals provided in the following may cause cell and
tissue injury. Eg: Poisons - Arsenic, Cyanide, Mercuric Salts, Air Pollutants,
Insecticide, Herbicide, Alcohol, Narcotic drugs
7. Infective - Infection by virus, bacteria, parasites, fungi, and other organisms,
8. Ischemia (Hypoxia) - Deficit of blood supply or Direct oxygen deficit
Thank You

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Basic principles of Cell injury.pptx

  • 1. Basic Principles Of Cell Injury And Adaptation Dr. Satheesh S,Pharm.D., Associate Professor Department of Pharmacy Practice
  • 3. Contents ● Introduction ● Definitions ● Homeostasis ● Types of Feedback System ● Cell Injury ● Causes of Cell Injury
  • 5. Introduction ● Pathophysiology is the study of biological and physical manifestations of diseases as the correlate with the underlying abnormalities and physiological disturbances ● Pathophysiology does not dealing with the treatment of diseases ● Instead it explains about the process within the body and it’s sign and symptoms ● It’s a advanced field of study beyond anatomy and physiology ● It’s concerned with the study of disease, infections, illness, and dysfunctions in the human body
  • 7. Definitions Disease: ● The term Disease refers to any conditions that impairs normal function ● I.e: Functional Abnormality ● It may be cause by external factors such as infectious disease or ● It may be cause by internal factors such as autoimmune disease. Disorder: ● Anatomical abnormalities or disturbances are known as disorder ● Like Fracture, Alzheimer and Diabetes, etc., ● Disorders are mainly categories into Mental disorder, Physical disorder, Genetic disorder, Emotional and Behaviour disorder and Functional disorder.
  • 8. Definitions Inflammation: ● It is a protective mechanism of the body to remove the injuries or stimuli or complex biological response of vascular tissue against the harmful stimuli like pathogen, damaged cells or irritants. ● Inflammation is not the synonyms of infection. But sometimes inflammation is caused by the infections Infection: ● Infection means the growth of parasitic organism within the body expect the normal growth of the usual bacterial flora in the intestinal tract
  • 9. Definitions Immunity: ● It is the defense mechanism to avoid the infection, disease or other unwanted biological invasion
  • 11. Homeostasis ● Ability to maintain relatively stable internal conditions despite a changing external environment. ● Dynamic state of equilibrium or balance ● Body is said to be in homeostasis when it's cellular needs are adequately met and functional activities are occurring smoothly ● Virtually every organ system plays a role in maintaining the internal environment ● Homeostasis regulatory mechanism consist of 5 parts
  • 12. Homeostasis ● Ability to maintain relatively stable internal conditions despite a changing external environment. ● Dynamic state of equilibrium or balance ● Body is said to be in homeostasis when it's cellular needs are adequately met and functional activities are occurring smoothly ● Virtually every organ system plays a role in maintaining the internal environment ● Homeostasis regulatory mechanism consist of 5 parts
  • 13. Homeostasis Regulatory Mechanism Effectors 05 ● Effectors are the cell or organ ● That responds according to the command of the control center via motor receptor Motor Receptor 04 ● It send the reply coming from integrated center to effector Integrated Center 03 ● It analyze the incoming message and send the reply via motor receptor (Brain and Spinal Cord) Sensory Neurons 02 ● It receives information from receptor and sends input messages to integrated center Receptors 01 ● It responds to a stimulus ● It monitors the change in control condition and send the input information to control center/ Integrated center via sensory receptors
  • 15. Types of Feedback System Types of Feedback System Negative Positive
  • 16. Negative Feedback System When the response of effectors opposes the original stimulus, it is called Negative Feedback because its neglect the stimulus An example for the negative feedback system is thermostat in home Temperature sensors turn on and off to maintain the air temperature within a specific range, condition range In the same way our body homeostasis mechanism control our body temperature
  • 17. Negative Feedback System ● Some stimulus (Stress) disrupts homeostasis (Control Condition) by an increasing in body temperature ● Due to this thermoreceptors (Temperature sensitive receptors) in the skin and brain activate and send input message through nerve impulse to the control center ● Control center analyze the input message and send output message to effectors (Skin).
  • 18. Negative Feedback System ● Effectors according to output message of control center increases sweating from sweat glands causes increased heat loss by evaporation ● Finally, decreases the temperature in the form of response and normalize the body temperature (Control Condition)
  • 19. Positive Feedback System The effectors add to the initial stimulus instead of negativen it, speeding up the process. ● Labor contraction is the best example for the Positive Feedback System ● Labor contraction force baby’s head or body into birth canal ● It produces effect on control condition and increase distension of cervix of uterus ● It activates the stretch receptors of the cervix and send input messages to the control center through sensory nerve impulse
  • 20. Positive Feedback System ● Control center activates the hypothalamus and pituitary gland and send the output message to increase oxytocin secretion in blood ● Oxytocin produces their effect on to the effector (cervix of uterus) and cause distension of cervix of uterus than the normal value to push the baby further into birth canal ● Birth of baby decreases distension of cervix of uterus and interrupts Positive Feedback Cycle
  • 22. Cell Injury ● Cell injury occurs as a results of Physical, Chemical or Biological insults or as results of vital substrate deficiency ● The term cell injury is used to indicate a state in which the capacity for physiological adaptation is exceeded. ● This may occur when the stimulus is excessive or when the cell is no longer capable to adapt without suffering some form of damage.
  • 23. Cell Injury ● The capacity for adaptation and the sensitivity to different types of injury varies according to cell type (i.e: Myocardial Cells and Neurons are highly sensitive to ischemic injury) ● Cell injury may be Reversible (Non-lethal damage which generally can be corrected by removal of stimulus) or Irreversible (Lethal damage) ● Genetic defect, abnormalities of several dietary factors, immune reaction, physical or chemical agent may cause the cell injury ● Commonly Ischemia and Hypoxia are the two forms of cell injury
  • 24. Reversible Cell Injury If the hypoxic or ischemic effect is for short duration then it produce reversible cell injury because this kind of effect is restore by the vascular circulation. Example: ● Coronary artery occlusion and ● Myocardial contractility, etc.,
  • 25. Reversible Cell Injury Some of the sequential biochemical and ultrastructural changes in reversible cell injury as follows 1. Depletion of ATP 2. Intracellular lactic acidosis and nuclear clumping 3. Effect on plasma membrane a. Failure of Na+ - K+ ATPase pump b. Failure of Ca++ pump 4. Decrease Protein Synthesis
  • 26. 1. Depletion of ATP ● ATP is the primary requirement for synthesis of protein, lipid and cell membrane, etc., ● In human body ATP is produced by aerobic and anaerobic process. ● Aerobic is carried out by the mitochondria whereas anaerobic carried out by glucose/glycogen ● In the ischemic condition, supply of oxygen and glucose both are get affected ● So decrease in the production of ATP results in fail in the production of protein, lipid and cell membrane, etc., leads to cell injury
  • 27. 1. Depletion of ATP ● In hypoxia, due to lack of oxygen supply there will be a formation of demand ● This may due to RBC disorder, Heart disease, Lung disease will form ● Generally anaerobic cell injury are less when compared with aerobic
  • 28. 2. Intracellular lactic acidosis and nuclear clumping ● Due to low oxygen supply aerobic ATP formation process get affected and mitochondria fails to work ● So anaerobic glycolytic pathway start to produce ATP ● This results in rapid depletion of glycogen and accumulate lactic acid ● It lower the intracellular pH due to intracellular acidosis and produce clumping of nuclear chromatin ● This effect release the lysosomes and it produce cellular digestion
  • 29. 3. Effect on plasma membrane ● Plasma membrane required phospholipid for continuous repair but due to lack of ATP fatty acid not form the phospholipids ● Due to this effect plasma membrane pumps get affected and the regulation of calcium, sodium and potassium get affected a. Failure of Na+ - K+ ATPase pump b. Failure of Ca++ pump
  • 30. a. Failure of Na+ - K+ ATPase pump ● Na+ - K+ ATPase pump is useful for the exchange of Na+ inside to outside and K+ outside to inside from the cell ● Lower ATP affect the activity of this pump and Na+ get accumulate inside the cell and K+ outside of the cell ● Accumulation of Na+ inside the cell retain the water and increase intracellular water level and hydrophobic swelling occur due to disruption in osmotic pressure
  • 31. b. Failure of Ca++ pump ● Accumulation of Na+ inside the cell produce affect in the intracellular level of Ca++ ● Excess Ca++ accumulate inside the cell as well as into the mitochondria leads to reversible cell damage
  • 32. 4. Decrease Protein Synthesis ● Lack of oxygen effect disturb the intracellular osmotic balance of the cell ● So endoplasmic reticulum and golgi apparatus swell up ● So the ribosome detach from the granular endoplasmic reticulum and it get inactive ● This effect decreases the synthesis of protein
  • 33. Irreversible Cell Injury ● Long lasting/persistence ischemic or hypoxic effect produce cell death or irreversible damage. ● If cells fails to reverse mitochondrial function as well as disturbance in cell membrane/ plasma membrane function cause irreversible cell injury It’s of two types I. Ca+ influx produce excitotoxicity into the cell a. Effect of activated phospholipase b. Effect of activated protease c. Effect of activated endonuclease II. Low pH of cell activate and release the lysosomal hydrolytic enzyme
  • 34. I. Ca+ influx produce excitotoxicity into the cell Large amount of intracellular Ca++ produce damage in mitochondrial cell wall as well as excitotoxicity (Activation of number of enzymes like phospholipase, endonuclease and protease, etc.,) This effect damage the cell structure such as component of cytoskeleton, plasma membrane and DNA etc.,
  • 35. a. Effect of activated phospholipase ● Activated phospholipase degrade the membrane phospholipids which is the main constituents of plasma membrane. ● As well as due to lack of ATP generation new phospholipid will not form and it aggregate the effects.
  • 36. b. Effect of activated protease ● Activated protease damage the cytoskeleton of the cell membrane leads to irreversible cell injury c. Effect of activated endonuclease ● Activated endonuclease damages the nucleoprotein as per below process ○ Condense or clumps the nucleus ○ Produce fragments of nucleus ○ Dissolve the nucleus
  • 37. II. Low pH of cell activate and release the lysosomal hydrolytic enzyme ● Lack of oxygen decrease the intracellular pH and it activate or release the lysosomal hydrolytic enzyme like Lactic Dehydrogenase (LDH), Creatinine Kinase (CK), hydrolyse RNAse, DNAse, Glycosidase, Phosphatase, Lipase, Amylase, Cathepsin, Etc., ● Activation of this enzyme digest the cellular components through the phagocytic effects and cause the irreversible cell injury.
  • 38. Causes of Cell Injury
  • 39. Causes of Cell Injury Types: 1. Genetic - Gene defects, Chromosomal Abnormalities 2. Nutritional - Deficiency or excess of dietary substance, e.g - Iron, Vitamins 3. Immune - Immune system works for foreign agents in some cases it will destroy the own cell . Example: a. Anaphylactic Reaction b. Autoimmune 4. Endocrine - Deficient or excessive hormone activity 5. Physical Agents - Mechanical trauma, Thermal damage, Irritation (UV and Ionizing)
  • 40. Causes of Cell Injury Types: 6. Chemical Agents - The chemicals provided in the following may cause cell and tissue injury. Eg: Poisons - Arsenic, Cyanide, Mercuric Salts, Air Pollutants, Insecticide, Herbicide, Alcohol, Narcotic drugs 7. Infective - Infection by virus, bacteria, parasites, fungi, and other organisms, 8. Ischemia (Hypoxia) - Deficit of blood supply or Direct oxygen deficit