2. CELL INJURY
Normal cells- basic unit of life .
They handle normal physiologic demands &
maintain steady status- “HOMEOSTASIS”.
Pathology –the study(logos) of
suffering(pathos).
3. Pathology- Bridging discipline –involving both
basic science & clinical practice.
Deals with –structural & functional changes in
cells/ tissues & organs that underlie disease.
Explains the ‘whys’ & ‘How’ of the ‘signs’ &
‘symptoms’ .
4. Pathology-
1. General- deals with basic reactions of
cells & tissues.
2. Systemic- deals with specific
responses of specialised organs &
tissues.
5. The four aspects of disease process –that
form the core of pathology are-
1. ETIOLOGY.
2. PATHOGENESIS.
3. MORPHOLOGY.
4. FUNCTIONAL DERANGEMENTS AND
CLINICAL MANIFESTATIONS.
6. Cell injury – defn- if the limits of adaptive
response to a stimulus are exeeded or when
the cell is exposed to an injurious agent
/stress, a sequence of events follows.
Cell injury- 2 types.
1. REVERSIBLE.
2. IRREVERSIBLE.
7. NORMAL CELL
stress/ injurious
stimulus
ADAPTATION-------------- CELL INJURY.
inability to adapt
10. REVERSIBLE CELL INJURY
Injury manifested as functional & morphologic
changes- reversible if the stimulus is
removed.
Hallmarks of reversible injury are-
1. reduced oxidative phosphorylation.
2. depletion of ATP.
3. cellular swelling- due to ion concn & water
influx.
11. IRREVERSIBLE CELL INJURY
Syn- CELL DEATH / NECROSIS.
The injured cells undergo morphologic
changes- both nuclear & cytoplasmic
changes.
12. CAUSES OF CELL INJURY
CAUSES- may range from the external gross
physical violence to internal endogenous
causes.
1. HYPOXIA- deficiency of oxygen- cell
injury by reducing aerobic oxidative
respn.
2.PHYSICAL AGENTS- Ex: mechanical
trauma, extremes of temp, radiation etc.
15. MECHANISMS OF CELL INJURY
The molecular mechanisms responsible for
cell injury are COMPLEX.
Reactions of the cell to injurious stimuli
depends on the TYPE OF INJURY, ITS
DURATION AND SEVERITY.
Also depends upon – TYPE, STATE AND
ADAPTABILITY OF THE CELL.
16. Susceptibility of cells to hypoxia
1. High – Ex: NEURONS (3 – 5 mins).
2. Intermediate- Ex: MYOCARDIUM,
HEPATOCYTES & RENAL
EPITHELIUM (30 min – 2hrs).
3. Low – FIBROBLASTS, EPIDERMIS &
SKELETAL MUSCLE (many hours).
17. ISCHAEMIC AND HYPOXIC INJURY
Sequence of events & ultrastructural
changes- extensively studied in humans,
experimental animals & in culture systems.
18.
19. FREE RADICALS AND CELL INJURY
Free radicals- chemical species that have a
single unpaired electron in an outer orbital.
Extremely reactive in nature.
Initiate autocatalytic reactions.
Intermediate oxygen species.
20. Three impt free radicals-
1. super oxide
2. Hydrogen peroxide- H2 O2.
3.Hydrxoyl radicals-OH.
Free radicals are toxic to tissues.
21. Free radical injury is final common pathway
in-
1.Chemical & Radiation injury.
2.Oxygen toxicity.
3.cellular aging.
4.Microbial killing by phagocytic cells.
5. Inflammatory damage.
6. Tumor destruction by macrophages.
22. DEGENERATIONS
DEFINITION: Morphologic changes resulting
from NONLETHAL OR REVERSIBLE
injury to cells are called as
“DEGENERATIONS”.
Two patterns are recognised under the light
microscope -
1.CELLULAR SWELLING.
2. FATTY CHANGE.
23. Other types of degenerations are-
1. HYALINE CHANGE.
2. MUCOID / MYXOID CHANGE.
24. CELLULAR SWELLING
SYN: hydropic change or vacuolar
degeneration.
First manifestation of almost all forms of
injury to cells- results from a shift of
extracellular water into the cell.
Difficult to appreciate with light microscope.
25. Cellular swelling – more evident in the whole
organ- causes pallor, increased turgor & wt of
the organ.
Micro : enlargement of cells & compression of
microvasculature of the organ. Ex: hepatic
sinusoids.
26. If water continues to accumulate within cells -
small clear vacuoles appear in the
cytoplasm.
Cytoplasmic vacuoles- indicates distended &
pinched off or sequestered segments of the
ER.
This pattern of nonlethal injury is called as
“HYDROPIC CHANGE” OR “VACUOLAR
DEGENERATION”
28. FATTY CHANGE
DEFINITION – abnormal accumulation of fat
within parenchymal cells.
SYN: Fatty degeneration/ fatty infiltration-
older terminology.
Fatty change- indicator of NONLETHAL OR
REVERSIBLE injury. But in excess it can
cause cell death – NECROSIS.
29. Fatty change – includes different
pathogenetic mechanisms.
Common organs- LIVER is the commonest
organ.
Other organs are- HEART, MUSCLE &
KIDNEY.
30. CAUSES OF FATTY LIVER
1. CHRONIC ALCOHOLISM –
commonest cause of fatty liver.
ALCOHOL – HEPATOTOXIN – alters the
mitochondrial & microsomal functions –
alteration in normal fat metabolism.
2. Protein malnutrition.
3. Diabetes mellitus.
31. Causes cont’d
4. Obesity.
5. Hepatotoxins.
6. Chronic illness.
7.Pregnancy – acute fatty liver- OFTEN
FATAL & RARE. Etiology is not
known.
32. PATHOGENESIS OF FATTY LIVER
1. Excessive entry of free fatty acids into
the liver. Ex: starvation.
2. Enhanced fatty acid synthesis.
3. Decreased fatty acid oxidation.
4. Increased esterification of fatty acids to
triglycerides.
5. Decreased apoprotein synthesis.
6. Impaired lipoprotein secretion.
34. Significance of fatty change –depends upon
the cause & severity of accumulation.
FATTY CHANGE - REVERSIBLE.
MORPHOLOGY - LIVER –mild fatty change
– may not affect the gross. Progressive
accumulation- wt- 3 to 6 kgs, bright,yellow,
soft & greasy.
36. Micro - in early stages – small fat vacuoles
appear in the cytoplasm around the nucleus.
Later - vacuolated hepatocytes with
peripheral nucleus(+).
“Fatty cysts” may be present.
39. HEART – fatty change can occur, due to
prolonged moderate hypoxia(anemia) &
some form of myocarditis(ex- diphtheritic)
due to severe hypoxia.
GROSS – bands of yellowed myocardium
with alternating bands of darker, red- brown
uninvolved myocardium-thrush breast or
tigered effect.
40. SPECIAL STAINS FOR FAT -
1. Oil –red ‘o’.
2. sudan iii/ iv.
3. osmic acid.
Importance- to differentiate with other
intracellular accumulations like water/
glycogen.
41. HYALINE CHANGE
HYALINE = GLASSY( hyalos = glass).
Definition – descriptive histologic term for
glassy, homogenous, eosinophilic
appearance of the material in H & E stained
sections.
Can be assosiated with heterogenous
pathologic conditions.
42. Hyaline change can be
1. INTRACELLULAR OR
2. EXTRACELLULAR.
INTRACELLULAR HYALINE -
A.hyaline droplets – seen in kidney – in
proximal tubular cells due to excess
reabsorption of plasma proteins.
43. B. Hyaline degeneration of voluntary
muscle (Zenker’s degeneration) – in
Rectus abdominalis – Typhoid fever.
C. Mallory’s hyaline – in ALD –
represents aggregates of intermediate
filaments of hepatocytes.
D. Nuclear/ cytoplasmic hyaline
inclusions- viral infns.
44. E. Russel’s bodies – represents
excessive immunoglobulins in plasma
cells.
F. Corpora amylacea – seen in prostate,
brain & spinal cord- aging process.
45. EXTRACELLULAR HYALINE
A. Common in leiomyomas of the uterus.
B. Old scar of fibrocollagenous tissue.
C. Arteriosclerosis in renal vessels - in
DM & hypertension.
D. Hyalinised glomeruli – in CGN.
IMPORTANCE of hyaline change – should
be differentiated from AMYLOID.