Etiology of cell injury

1. SUBJECT : PPATHOPHYSIOLOGY
TOPIC : ETIOLOGY OF CELL INJURY

2. ETIOLOGY OF CELL INJURY
Genetic Acquired
1. Hypoxia and ischemia
2. Physical agents
3. Chemical and drugs
4. Microbial agents
5. Immunological agents
6. Nutritional derangement
7.Aging
8.Psychogenic
disease
9.Iatrogenic
causes
10.Idiopathic
diseases
1. Developmental
defects
2. Cytogenetic (
karyotype )
Defects
3. Single gene –
Defects
4. Multifactorial
Inheritance
Disorders

3. A) GENETIC CAUSE-
1.DEVELOPMENTAL DEFECTS : Errors in morphogenesis
Birth Defects
Chemical Physical
Biological
Agent
Drugs
2.CYTOGENETIC ABNORMALITIES:
 Numerical Defects
 Structural Defects

4.  Numerical Defect:
 Polyploidy: Number of chromosomes multiple of haploid
number,
e.g. Triploid 3N (69 chromosomes), Tetraploid 4N (92
chromosomes)Normally occurs in megakaryotes, dividing living
cells, somatic cells of conceptus. Total disjunction of
chromosomes during mitosis/meiosis.
• Aneuploidy: Number of chromosomes not exact multiple of haploid
number
Aneuploid
y
Hypodiploid
(2N-1)
Hyperdiploid
(2N+1)
45 chromosomes-
Monosomy
47 chromosomes-
Trisomy

5.  Causes of aneuploidy:
 Nondisjunction during 1st meiotic division :
Failure of a pair of homologous chromosomes to separate

6.  Nondisjunction in meiosis -2nd
Failure of sister chromatids to separate.

7.  Nondisjunction in mitosis:
Failure of sister chromatids to separate

8.  Anaphase lag:
Form of disjunction involving single pair of chromosomes in
which one chromosome in meiosis / chromatid in mitosis fails
to reach to the pole of dividing cell at same time .

9.  Structural defect:
Structural
defect
Abnormality in gametogenesis
All somatic cells
Hereditary
transmissible
disorder
Somatic
mutation
Certain cancer
causes
transmissio
n

10. Balanced Unbalanced
Inver
sion
Reciprocal
translocat
ion
Dele
tions
Is
chro
moso
me
Ring
chro
mos
ome
Recip
rocal
Roberts
onian
Translo
cation
STRUCTURAL
ALTERATION
 Balanced structural alteration : No change in total number
of genes/genetic material
 Unbalanced structural alteration : Gene rearrangement
results in loss /gain of genetic material

11. Various
cancer
Congenital
malformati
on
Germ
cell
Somatic
affec
t
MUTATION PROCESS
3. Single gene
defects:
 Mutation: Permanent change in DNA
Inherited
disease
Transmission to progeny

12. TYPES OF
MUTATION
Trinucleotide repeat mutation :
Amplification of a sequence of 3
nucleotide
Frameshift
mutation:
Insertion/dele
tion 1 or 2
base pairs in
DNA sequence
Stop codon mutation : Point
defect protein chain is
prematurely terminated
Point
mutation :
Substitution
of a single
nucleotide
base by a
different
base

13.  Inheritance
pattern:
Autosomal dominant
inheritance defect:1
mutant & 1 normal
gene
Autosomal recessive
inheritance defect: 2
mutant genes in
progeny
X-Linked disorder
: mutant genes of
X-chromosomes
Inheritance Pattern abnormalities
4.Multifactorial inheritance:
1) Combined effect of genetic composition 2) Environmental influences
e.g. pyloric stenosis , diabetes mellitus , hypertension , coronary heart
disease.
B)Acquired causes of cell injury -
Hypoxia : Reduced in blood supply

14. Hypoxia
Disorders of
O2 carrying
RBCs
Increased O2
demand of
tissue
Interruption
CO
Poisoning
Heart ,
Lungs
Diseas
e of
organ
Exercise
Anemia
Ischemia
2. Physical agent:
1) Mechanical trauma (e.g. road accidents) 4) Radiation (UV ,ionizing)
2)Thermal trauma (e.g. heat , cold ) 5) Rapid changes in
3)Electricity Atmosphere
1. Hypoxia:

15. 3. Chemicals and drugs:
1. Chemical Poisons such as Arsenic
,Mercury, Cyanide, etc.
2. O2 at high concentration
3. Strong acids and bases
4. Social agents such as Narcotic Drugs,
Alcohol
5. Environmental Pollutants
6. Therapeutic administration
of drug
7. Insecticides and Pesticides
8. hypertonic glucose and
salts.
Microbial Agent
Bacteria e.g.
Salmonella
Typhi
Myobacterium
Tuberculosis
Protozoa e.g.
Plasmodium
Vivax
Fungi e.g.
Fungus
Aspergillus
Candida
Albicans
Metazoan
Helminthes
e.g.
Ascaris
Viruses
e.g.
HIV Virus
Polio
Virus
Hepatitis
Virus
4.Microbial Agent:

16. 5.Immunologic agents: Protect host against various injurious
agent, it may cause cell injury
Effects of immunological agents
Hypersensitivit
y : Protective
role, but has a
harmful effect
Anaphylactic reaction
: Abnormal and serious
immunological allergic
reaction i.e. rapid
onset and may cause
death
Autoimmune Disease :
Abnormal
immunological
response against an
antigen i.e. part of
body
6.Aging: Senescence
Cell death
Repair
Replication
Death of individual
Impaired ability of cell
Do not undergo

17. Excess of nutrients
Deficiency of nutrients
Nutritional imbalance
Heart Disease
Obesity
Protein
calorie
Marasmus
,
Kwashior
kor
Lipid,
Glucose
Starvati
on
Atherosclerosis
Hypertension
Anemia
Minerals
Lea
ds
to
Lea
ds
to
Lea
ds
to
Such as
7.Nutritional
Imbalance:

18. Smoking
Anxiety
Mental
Stress
Ischemic
heart
disease
Chronic
bronchiti
s
Drug
Addiction
Alcoholis
m
Psychogenic/mental diseases e.g. Depression, schizophrenia
Lung
Cancer
Liver
Damag
e
Hyperte
nsion
Peptic
ulcer
Frustratio
n
Mental
Strain
Overwork
8.Psychogenic Disease:
Leads
to
Results in

19. 9.Iatrogenic causes :
Errors in judgement of by the physician
Untoward effect of
administered therapy
(Drug, radiation)
Occurrenc
e of
Disease
Death
10.Idiopathic Disease: Exact
Etiology is undetermined e.g. many
cancers