Theme - 2

Adaptation, injury and cell death

PATHOPHYSIOLOGY
Dr. Javier Pereda
 Table of contents
Introduction
1- Cell degeneration
2- Cell adaptation
3- Irreversible damage
4- Basic mechanisms of cell damage and death
5- Irreversible damage: cell death
6- Necrosis
7- Apoptosis
8- Apoptosis and disease
9- Differences between necrosis and apoptosis

Prof. J. Pereda
 Introduction

Normal cells are able to handle normal

physiological stimuli.

HOMEOSTASIS

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 1- Cell degeneration (I)

Definition:
 Regressive process in which cells deteriorate with
changes at different levels.

Types of cell degeneration

 Hydropic degeneration
• Decrease of ATP, sodium-potassium pump does not
work well. Increase of H2O.
 Intracellular accumulation of substances
• Excessive normal substance • Exogenous substance
• Abnormal substance
Prof. J. Pereda
 1- Cell degeneration (II)
 Cause is cell aggression

 Consequence depends on the degree of

aggression

1) Reversible damage
-
2) Cellular adaptation
degree of aggression
(of degeneration) 3) Irreversible damage
+
Cell death
Prof. J. Pereda
 2- Cell adaptation
Long-term damage Not adaptations:
Neoplasia
 Not always positive Aplasia

 Changes in size and function

ATROPHY: HYPERTROPHY:
decreased size (and function) Increased size (and function)

NORMAL
HYPERPLASIA:
Increased number
(in proportion to stimuli) METAPLASIA:
Change in cellular type

DYSPLASIA
Disorder in cellular number and type

Prof. J. Pereda
 3- Irreversible damage
 If the injury is too strong and cell cannot adapt:
irreversible damage leading to cell death.

Point of no return

 Death appears as a consequence of cell damage

mainly by:
Ischemia (hypoxia), xenobiotics, immunity reactions, genetic
disorders, nutritional unbalances …

Prof. J. Pereda
 4- Basic mechanisms of cell damage and death

1. Deficit in aerobic respiration:

ATP depletion
2. Loss of the intracellular calcium
homeostasis
3. Generation of reactive oxygen species:
oxygen free radicals
4. Alteration in cell permeability

Prof. J. Pereda
5- Irreversible damage: cell death

TYPES OF CELL DEATH

NECROSIS APOPTOSIS

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 6- Necrosis (I)
It is the most common type of cell death after
exogenous stimuli. It is characterized by cellular
disruption, protein denaturalization and organelle
disruption.
Cause:
 Intense and fast injury.
Mechanism:
 Mitochondrial damage.
–Decrease of energy.
 Membrane disruption.
–Decrease of osmotic regulation or capacity.

Prof. J. Pereda
 6- Necrosis (II)
Types:
• Liquefactive necrosis
– No destruction of catalytic enzymes.
• Coagulative necrosis.
– Enzymatic denaturalization by acidosis: ischemia.
• Caseous necrosis.
– Typical of tuberculosis: white and friable like clumped cheese.
 When a large necrosis appears (limbs…) : gangrene
– It may be accompanied by an infectious component.
• Dry gangrene.
• Wet gangrene. If anaerobics: gas gangrene
Role in the disease:
• Crucial role, depends on cellular type.
• Normally associated with INFLAMMATION.
• Difficult to treat. Not regulated.

Prof. J. Pereda
 7- Apoptosis (I)

Voluntary “cellular suicide” or induced by the

elimination of non desired cells, occurring in
embryogenesis, in physiologic and pathologic
processes. Sometimes cohabit with necrosis.
It has been named “programmed cell death”

Cause:
 Irreversible damage leading not to necrosis (so it
is a less severe aggression).

Prof. J. Pereda
 7- Apoptosis (II)
Cellular changes in apoptosis.
1) Citoplasmatic volume is decreased
2) Phosphatidilserine is externalized
3) Zeiosis (or blebbing)

Apoptotic bodies
4) Characteristic changes in the nucleus
a) First is condensed
b) Then is located peripherally
c) Finally is fragmented into spheres

DNA is fragmented in regular sizes

Destiny phagocytosis
No release = no inflammation Prof. J. Pereda
 7- Apoptosis (III)
Mechanisms: B) “death receptors” pathway
e.g. TNF-α C) Direct pathway
(granzimes)

extracellular

citoplasm
A) Mitochondrial pathway

Initiator caspases

Executioner caspases
Cytochrome C (most imp. caspase 3)
- Directly Apoptosis
- Controlled by BCL-2 execution
family Protease activation and DFF Prof. J. Pereda
 8- Apoptosis and disease
Important physiologic role in:
 Embryogenesis
 Cellular renewal
 Physiologic atrophies
 Immune system
Pathologic role when:
 Apoptosis is increased:
• Infectious diseases, degenerative diseases,
ischemia...
 Apoptosis is decreased:
• Virus, autoimmune diseases, neoplasia…
great hope…
Prof. J. Pereda
9- Differences between necrosis and apoptosis
Necrosis Apoptosis
Names Cellular assassination Cellular suicide or
programmed cell death
Causes Exogenous Endogenous or exogenous

Changes Citoplasmatic expansion and Citoplasmatic contraction and

membrane disruption finally zeiosis (blebbing).
Nucleus with secondary Nucleus with fragmented
injuries ADN

Resolution Inflammatory response NO inflammatory response

Phagocytic recognition

Meaning Pathologic Control system

Pathologic response
https://www.youtube.com/watch?v=witLM--V2v8
Prof. J. Pereda