4. INTRODUCTION
“All organ injuries start with
structural or molecular alterations
in cells” concept began by Virchow
in 1800's
•modern study of disease attempts
to understand how cells react to
injury, often at the subcellularor
molecular level, and how this is
manifested in the whole animal.
Scanning Electron Micrograph of
Blood Cells Caught in a Blood Clot
•rbc’s -flattened discs with smooth
surface.
•white cells –spherical with
roughened surface.
5.
6. INTRODUCTION
Structures of living systems are not
constant
They are destructured and restored
continuously
All living organisms absorb and
extract proteins, lipids (fats),
carbohydrates, and their
components as well as water, ions,
and pigments
7. definitions
1) Homeostasis
•cells maintain normal structure & function in response to
physiologic demands.
2) Cellular Adaptation
•as cells encounter stresses they undergo functional or
structural adaptations to maintain viability / homeostasis.
•respond to some stimuli by increasing or decreasing specific
organelle content.
•adaptive processes: atrophy, hypertrophy, hyperplasia and
metaplasia.
8. definitions
3) Cell Injury
•if limits of the adaptive response are exceeded or if
adaptation not possible, a sequence of events called cell
injury occurs.
a) Reversible Cell Injury
•removal of stress results in complete restoration of structural
& functional integrity.
b) Irreversible Cell Injury / Cell Death
•if stimulus persists or is severe enough from the start, the
cell suffers irreversible cell injury and death.
• 2 main morphologic patterns: necrosis & apoptosis.
9. CELLULAR INJURY
ETIOLOGIC AGENT MAY BE EVERY
ONE EXOGENIC OR INTRAGENIC
BUT CHAIN OF CELLULAR CHANGES
CONSISTS OF STAGES AS FOLLOW:
1. ADAPTATION
2. REVERSIBLE CHANGES
3. IRREVERSIBLE CHANGES as NECROSIS(CELLULAR DEATH)
4. autolysis and heterolysis
12. Cell Membranes
why so easily injured?
1.
2.
3.
Membrane is in contact with the
external environment:
- sustains “trauma”
- extracellular oxidants, proteases,
etc.
Requires a constant supply of ATP for
normal function (ion pumps)
Lipid molecules in the membrane are
easily oxidized and support oxidative
chain reaction called lipid peroxidation
14. CELLULAR INJURY
Reversible changes or cellular
degeneration or parenchymal dystrophy
According to metabolic disturbance there
are protein, fatty, carbohydrate, and ion
degenerations.
According to localization there are
parenchymal (cellular), mesenchymal
(stromal- -vascular), and mixed reversible
changes or degenerations
15. CELLULAR INJURY
Causes or etiology
Hypoxia
Ischemia
Physic agents
Chemical agents including medicine, drug
Infective agents
Immunologic reaction
Genetic injury
Nutrition disbalance
16. CELLULAR INJURY
Mechanisms of reversible injury
Decomposition of membranes
Hyper infiltration of substances
(intracellular accumulation)
Unnatural syntheses
Disbalance of calcium metabolism
ATP depletion
Free radical- induced injury
induced injury
17. CELLULAR INJURY
Cellular injury depends on cell:
1. type (myocardial cells dies in20- 30
min. ,but epidermis cells dies in
weeks,
after cause (etiologic agents ) acted.
2.genetic makeup
3.adaptability ( hepatic cells are more
adaptive cells, then neurons)
4.status( normal or hypertrophic)
18. CELLULAR INJURY
Cellular injury depends on
injury:
1. type (ischemia or infective
agent)
2.its duration
3.its severity
19. REVERSIBLE
Cellular injury
INTRACELLULAR RESPONSE INCLUDS
Aggregation of intramembranous particles
Endoplasmic reticulum swelling
Dispersion of ribosomes
Cell swelling
Clumping of nuclear chromatin
Mitochondrial swelling
Small densities within mitocondria
25. REVERSIBLE
Cellular injury
Classification according to cellular
disproteinosis
Cellular swelling or hydropic
(vacuole)
dystrophy or degeneration
Hyaline droplet dystrophy or
degeneration
Hyper keratinization
26. Cellular swelling or
hydropic dystrophy
Ions disbalance between sodium
and potassium with water bubble
formation
Protein infiltration within cells
Cellular membranes destruction
27. Renal tubular epithelium –
reversible ischemic injury
Loss of microvilli
Surface blebbing
Slight swelling of
mitochondriaClum
ping of nuclear
chromatin
31. Cellular swelling or
hydropic dystrophy
The tubular vacuolization and
tubular dilation here
is a result of the
toxic effect of
ethyleneglycol
poisoning
32. Hyaline droplets dystrophy
or degeneration
Here are Mallory
bodies (the red
globular material)
composed of
cytoskeletal filaments
in liver cells
chronically damaged
from alcoholism
33. INTRACELLULAR ACCUMULATION
FATTY CHANGE (STEATOSIS)
PARENCHYMAL LIPIDOSIS
IS CHARACTERIZED BY ABNORMAL
ACCUMULATION OF TRIGLYCERIDES
WITHIN PARENCHYMAL CELLS
ORGANS:
THE LIVER,
THE MYOCARDIUM,
THE KIDNEYS.
34. FATTY CHANGES
IN THE LIVER
- ETIOLOGY IS TOXINS, PROTEIN
MALNUTRITION, DIABETES
MELLITUS, OBESITY AND ANOXIA.
- PATHOGENESISIS IS
DISBALANCE BETWEEN REMOVE,
UTILISATION AND EXCRETION
OF LIPIDS BY HEPATOCYTES.
35. PATHOGENESIS OF
FATTY LIVER
EXCESS ABSORPTION OF fatty
acids and triglycerides
Reduced Utilization of them on
mitochondrii
Decrease in apoprotein production
36. THE STAIN FOR LIPIDS IS
NAMED SUDAN THREE
Gross sample
Micro sample
h/e stained
37. FATTY LIVER
Hepatic liposis,
higher magnification.
The well-delineated
lipid filled
cytoplasmicvacuoles
causing swelling of
the hepatocytes,
usually pushing
nucleus to the
periphery of the cell.
Note, how the
vacuoles can be
single and large or
multiple and small.
38. FATTY CHANGES IN THE
HEART
ETIOLOGY HYPOXIA, INTOXICATION .
PATHOGENESIS LACK of OXYGEN LEAD TO
decreasing oxidative phosphorylation
anaerobic glycolysis decreasing ATP
synthesis mitochondria destruction
inhibition of fatty acid oxidation
toxins cause severe damage of
membranes and enzyme systems
39. Prolonged moderate hypoxia results in
focal intracellular fat deposits
APPEARANT BANDS OF
YELLOWED MYOCARDIUM
ALTERNATING WITH
BANDS OF DARKER, RED
BROWN UNINVOLVED HEART
TIGERET EFFECT´ ± TIGER
HEART
Severe fatty change is produced
by profound hypoxia with
diffused yellow±colored
myocardium
41. FATTY CHANGES IN THE
AORTAAND LARGE ARTERY
Atherosclerotic plaque
contains
cholesterol and its
esters within
macrophages and
smooth muscle cells
(foam cells).
After cell death,
cholesterol and its
esters are seen out of
cells.
44. Consequences of Injury
1.
2.
3.
No long term effects- - the cell
damage is repaired, the effects of the
injury are reversible.
The cell “adapts” to the damaging
stimulus.
The cell dies, undergoing necrosis.
The damage is irreversible.
45. IRREVERSIBLE CELL INJURY
the morphologic appearance is due to
2 concurrent processes:
1.
denaturation of proteins
2.
enzymatic digestion
47. Coagulation Necrosis
•most common manifestation of cell death.
•characteristic of hypoxic / ischemic death of
cells in all tissues (except brain).
•on LM, basic outline of the coagulated cell
persists at least a few days.
- protein denaturation predominates over
enzymatic digestion.
•necrotic cells eventually removed by
leukocyte proteolysis & phagocytosis.
48. Coagulation Necrosis
Gross Appearance
•architecture resembles
normal tissue, but
colorant texture are
different.
•lighter in color (pale)
-due to coagulation of
cytoplasmic proteins
and decreased blood
flow (eg infarcts).
•usually firm.
•tissue may be swollen
or shrunken.
•may see a local vascular
/ inflammatory
reaction to necrotic
tissue.
49. Coagulation Necrosis
Microscopic Appearance
•original cell shape &
tissue architecture is
Preserve die dead cells
resemble an eosinophilic
"shadow" of the original
cells.
•cytoplasm: increased
eosinophilia (H&E
stain)usually hyalinized
(homogeneous glassy
appearance) may be
mineralized.
a) Coagulation Necrosis
•nucleus:
1.
karyolysi
2.
pyknosis
3.
karyorrhexis
51. Skeletal muscle
note coagulation necrosis of
myofibers characterized by
fragmentation and
hyalinization; also note
extensive mineralization
(blue-purple staining)
52. Liquefactive Necrosis
•when enzymatic digestion of necrotic cells predominates.
•esp bacterial infections; neutrophils contain potent
hydrolases.
•in hypoxic damage (and other types of damage) of the CNS.
•affected tissue is liquefied to a soft, viscous, fluid mass.
•in acute inflammation, the liquid is often mostly dead WBC’s
(pus).
•may see degenerate neutrophils and/or amorphous necrotic
material.
56. Gangrenous Necrosis
•definition= necrosis
(usually ischemic) of
extremities, eg digits, ear
tips.
•dry gangrene=
coagulation necrosis of
an extremity.
•wet gangrene= when
the coagulative necrosis
of dry gangrene is
modified by liquefactive
action of
saprophytic/putrefactive
bacteria.
57. Fat Necrosis
•distinguished by its location in
body fat stores.
•etiology: inflammation (eg
pancreatitis), Vit E deficiency,
trauma, idiopathic
59. Summary
All human disease occur because of
cell/tissue injury
Membranes-outer and mitochondrial
are key targets
Many early steps are reversible
Cell death follows going beyond a
point of no return -drop in pH, rise in
Ca2+
