basic principle to cell injury and cell adaption , pathophysiology, b pharmacy, rahul molla,

1. Basic Principle to Cell Injury and
Cell Adaptation
By
Rahul Molla
M. Pharmacy (J U )
Roll no -002211402026
Under the guidance
of
Dr. Sanchita Mandal
(Department of Pharmaceutical Technology)

2. CONTENTS
Introduction Homeostasis
Feed back
system
Causes of
cell injury
Pathogenesis
Morphology
of cell injury
Cell swelling
Enzyme
leakage and
cell death
Acidosis and
Alkalosis
Electrolyte
imbalance

3. Pathophysiology
Pathophysiology is the branch of medical science which deals with reason behind any
disease and associated changes occurred at the level of cell,tissue,and organ which in
turn give rise to presents the sign and symptoms in the patient .
It is the scientific study of structure and function of the body suffering from any
diseases.
Important terminology :
Lesions are the characteristics changes in tissue and cell due to diseases in living
organism .
Morphology its nothing but the outer appearance of diseased tissue like urine or
blood samples.
Etiology It includes the reasonable causes and factors what actually leads to
diseased state in the patients .
Pathogenesis it refers to the development stages or phases of any disease .

4. Homeostasis
 Homeostasis denotes the maintaince ,or regulation ,of vital internal variables in a state of
relative constancy . Automatic cellular mechanism ,neural and endocrine controls , and
behaviour all contribute importantly to homeostasis.
 Homeostasis refers to the ability of an organism to maintain the internal environment of the
body within limits that allow it to survive .
 It also refers the self regulating processes that return critical systems of the body to a set
point within a narrow range of operation ,consistent with survival of the organism . Its
highly developed in warm blooded animals living on land ,which must maintain body
temperature , fluid balance, blood pH And oxygen tension within rather limits while same
time provide energy to maintain homeostasis .

5. Feedback mechanism
 A feedback mechanism is a physiological regulatory system that either returns the body
to a normal internal state or less commonly ,brings an internal system further away
from the homeostasis.
A ) Negative feedback
B) Positive feedback
 Component : receptor , control center , and effector .
 Negative feedback : It occurs when the original effect of the stimulus is reduced by the
output. Negative feedback mechanism normalizes the things when they start becoming
too extreme.
Eg: the thyroid gland is regulated by a negative feedback mechanism.

6. Positive Feedback Mechanism
A positive feedback mechanism loop is a pathway that causes an effect that exceeds far beyond
the state of homeostasis.
It amplifies part of a physiological system that is already outside the homeostatic range .
Positive feedback mechanism exist rarely.
They attempt to bring the steady state of homeostasis.

7. Cell Injury
 Cell injury can be defined as an alteration in cell structure or biochemical functioning resulting
from some stress that exceeds the ability of the cell to compensate through normal physiologic
adaptative mechanism .
Types : 1) Reversible cell injury : IT implies that if once the stress is removed, the cell can return to
its original 2) irreversible the stressful stimuli is excessive or persistent ,the cellular damage becomes
.irreversible and cell undergoes cell death .
 Causes of cell injury : A) Acquired causes ;
 Hypoxia and ischemia .
 Physical agent
 Chemical agents and drugs
 Microbial agent
 Immunologic agents
 Psychological factors

8. 1.Hypoxia and Ischemia
 Hypoxia refers to inadequate supply of oxygen to cell or tissue which leads to cell injury by
reducing aerobic oxidative respiration .
 Hypoxia is one of the most important and common cause of cell injury and cell death .
Depending on the severity of the hypoxic state ,cells may adapt undergo injury or die .
Reason : Reduced blood supply ;ischemia Anemia
Carbon monoxide poisoning
Increased oxygen demand of tissues .
2.Physical agents : Physical agents may damage or injure cell or tissues ,which may lead
to cell death . Some of the physical agents are mentioned below ; it includes
1. Mechanical trauma (road accident, falls from a height ,railway accident ) .
2. 2. Thermal trauma ( heat and cold temperature to the body parts )
3. 3.Radiation .
4. 4. sudden change in pressure of the atmosphere .

9. Chemical agent and drugs
 Chemical and drugs mainly causes cell injury by alteration the
structure of cellular organs like , by changing the permeability of
cell membrane ,osmotic homeostasis, or in the functional capacity
impairment of the vital enzyme or cofactor.
 It includes , chemical poisons, environmental pollutants, toxic
substances , hyper oxygen concentration in cell, narcotic drugs
,pesticides etc.

10. Microbial agent
 A lots of microbial agents are present in the environment , which
infect the cell and leads to cellular damage and finally leads to cell
death .I t includes mainly viruses, bacteria, fungi, protozoa etc.

11. Immunologic agents
 The immune system serves as as essential function in defence against
pathogen , but immune reaction may cause cell injury.
 Injurious reaction to endogenous self antigens are responsible for several
autonomous diseases . It includes hypersensitivity reaction, anaphylactic
reaction ,autonomic diseases ( Parkinson's disease, rheumatoid disease) .

12. Pathogenesis
Injury to the normal cell by one or more of the above listed etiologic agents may
result in a state of reversible or irreversible cell injury. The underlying
alterations in biochemical systems of cells for reversible and irreversible cell
injury by various agents is complex and varied. However, in general, the
following principles apply in pathogenesis of most forms of cell injury by various
agents:
1. Type ,duration and severity of injurious agents :
The extent of cellular injury depends upon type, duration and severity of the stimulus e.g.
small dose of chemical toxin or short duration of ischemia cause reversible cell injury while
large dose of the same chemical agent or persistent ischemia leads to cell death .
2.Type,status and adaptability of target cell : The type of cell as regards its
susceptibility to injury, its nutritional and metabolic status, and adaptation of the cell to
hostile environment determine the extent of cell injury .

13. Pathogenesis
 3. Underlying intracellular phenomena: irrespective of other factors,
following essential biochemical phenomena underlie all forms of cell injury:
 i)Mitochondrial damage causing ATP depletion.
 ii) Cell membrane damage disturbing the metabolic and trans-membrane
exchanges.
 iii) Release of toxic radicals.
 4. Morphologic consequences: All forms of biochemical changes underlying
cell injury are expressed in terms of morphologic changes . The morphologic changes of
reversible cell injury (e.g. hydropic swelling) appear earlier than morphologic
alterations in cell death (e.g. in myocardial infarction.

14. Morphology of cell injury
 Depending upon the severity of cell injury, degree of damage and residual
effects on cells and tissues are variable. In general, morphologic changes in
various forms of cell injury can be classified ,
 1. morphology of reversible cell injury :
 a. Hydrophobic changes ( cell swelling and vascular degeneration ).
 b. Fatty changes .
 c. Hyaline changes .
 d. Mucoid changes .
 2. Morphology of irreversible cell injury :
 a . Narcosis
 b. Apoptosis
 3. Intracellular accumulation

15. Cell swelling
 cell swelling is acute reversible changes resulting as a response to nonlethal injuries . It is
also known as hydropic changes which means accumulation of water within the cytoplasm
of the cell . For gross appearance of the affected organ , its termed as cell swelling .

16. Acidosis and Alkalosis
 During metabolism of cells, carbon dioxide and metabolic acids are produced.
CO2 combines with water to form carbonic acid. The role of bicarbonate
buffering system in the extracellular compartment has already been stated
above. In order to have acid-base homeostasis to maintain blood pH of 7.4, both
carbonic acid and metabolic acids must be excreted from the body .
 Metabolic acidosis: A fall in the blood pH due to metabolic component is
brought about by fall of bicarbonate level and excess of H+ ions in the blood. This
occurs in the following situations:
 Production of large amounts of lactic acid (lactic acidosis ) e.g. in vigorous
exercise,
 shock.
 Uncontrolled diabetes mellitus (diabetic ketoacidosis).
 Starvation.
 Chronic renal failure.
 Therapeutic administration of ammonium chloride or acetazolamide .

17. Metabolic alkalosis
 A rise in the blood pH due to rise in the bicarbonate levels of plasma and loss
of H+ ions is called metabolic alkalosis. This is seen in the following
conditions:
 Severe and prolonged vomiting.
 Administration of alkaline salts like sodium bicarbonate.
 Hypokalemia such as in Cushing’s syndrome, increased secretion of
aldosterone.
 Clinically, metabolic alkalosis is characterized by depression of respiration or
depressed renal system . In this situation the bicarbonate level in the blood
get increased .

18. Electrolyte Imbalance
 HYPONATRAEMIA
 A. Gain of relatively more water than loss of sodium
 i. Excessive use of diuretics
 ii. Hypotonic irrigating fluid administration
 iii. Excessive IV infusion of 5% dextrose
 iv. Psychogenic polydipsia
 v. Large volume of beer consumption
 vi. Addison’s disease
 B. Loss of relatively more salt than water
 i. Excessive use of diuretics
 ii. Renal failure (ARF, CRF)
 iii. Replacement of water without simultaneous salt replacement in conditions causing
combined salt and water deficiency.

19. Electrolyte imbalance
 HYPERNATRAEMIA
A. Gain of relatively more salt than loss of water:
i. IV infusion of hypertonic solution
ii. Survivors from sea-drowning
iii. Difficulty in swallowing e.g. esophageal obstruction Excessive sweating (in deserts, heat stroke)
B. Loss of relatively more water than salt:
I. Diabetes insipidus
II. Induced water deprivation (non-availability of water, total fasting)
III. Replacement of salt without simultaneous water replacement in conditions causing combined
salt and water deficiency .
 HYPOKALAEMIA
 A. Decreased potassium intake:
 i. Anorexia ii. iii. IV infusions without potassium Fasting iv. Diet low in potassium
 B. Excessive potassium excretion :
 i. Loss from GI tract (e.g. vomiting, diarrhoea, laxatives) ii. Loss from kidneys (e.g.
excessive use of diuretics, corticosteroid therapy, hyperaldosteronism, Cushing’s
syndrome) iii. Loss through skin (e.g. profuse perspiration) iv. Loss from abnormal
routes (e.g. mucinous tumours, drainage).

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