Definition of death,

signs of death,

necrosis, apoptosis

„Death is law, not punishment”(Seneca)

Clinical death - temporary cessation of

circulation/oxygen supply

- it is reversible for a short time

(loss of oxygen < 4-5 min)

Biological death - irreversible

(no cerebral electric activity)

possibility of organ transplantation

Suspicion signs of death:

pallor mortis (paleness)

algor mortis (cooling)

Death as a legal category

Determination of death is a task of medical doctor

Obligatory administrative tasks:

Death certificate

Toe tag

Obligation for action

Natural death

Extraordinary death

Pathological signs of death

livores mortis (lividities)

- due to gravitation

- due to imbibition

- putrefaction

muscle stiffness (rigor mortis)

Irreversible tissue damage

Necrosis Apoptosis

Not programmed Genetically programmed

Does not require energy Energy requirement

Ruptured membrane structrures Intact membrane structures

(DNA-fragmentation)

Accompanied by inflammation reaction No inflammation

Two major mechanisms:- death receptors

- mitochondrial route

The same agent may produce either apoptosis or necrosis, depending on its concentration

Necrosis

Circumscribed death of tissue/organ within a living organism

Cause: The strength of the harmful factor exceeds the compensatorycapacity of the given tissue

a./ endogeneous causes:

- vascular causes (obstruction of arteries, veins) – thrombosis, embolia

- hypoxia (brain, centers of malignant tumors)

- neural effects (Raynaud-phenomenon, diabetes mellitus)

- immunological causes (immune complexes, C3-activation)

- mechanical causes (prolonged compression) – decubitus

b./ exogeneous causes:

- chemicals (poisons, cytostatic drugs)

- irradiation

- electricity

- freezing

- biological agents

karyopyknosis

karyorrhexis

karyolysis

demarcation zone

Molecular mechanisms of the necrosis

Variable

- depends on the given noxas (severity, duration)

- depends on the given tissue/organ

irreversible damage: brain 4-5 min

myocardium 20-30 min

limbs 2-3 hours

Site of damage:

- mitochondrium (discontinuation of ATP-production)

- cell membrane (Na/K-pump damage)

- protein synthesis

- cytoskeleton

- genetic structures

Mechanisms:

- ATP-depletion

- Ca-influx into the cell (activation of intracellular enzimes)

- production and accumulation of free radicals (ROS)

- increased membrane permeability

- damaged DNS-repair

Apoptosis

Physiologic role:

- resorption of buccopharyngeal membrane

- thymic involution

- resorption of primitive kidney

- lumen formation in the bowel atresia

- resorption of the membrane between fingers syndactyly

APOPTOSIS INDUCTION IS AN IMPORTANT THERAPEUTIC GOAL IN CASES OF MALIGNANT TUMORS

Necrosis and apoptosis sometimes

dangereous, sometimes desirable

chemoembolisation

cytostatic treatments

local alcohol-injection

electrocoagulation