cell

1. CELL INJURY AND
ADAPTATIONS

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

8. CELLULAR ADAPTATIONS
 1.Hyperplasia & Hypertrophy- Ex- increased
demand/ increased stimulation.
 2.Atrophy- Decreased nutrients.
 3. Metaplasia- chronic irritation (chemical
or physical)

9. NORMAL, HYPERTROPHY &
DILATED HEART

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.

13.  3. CHEMICAL AGENTS & DRUGS-
Ex: glucose, salt, acids etc.,
 4. INFECTIOUS AGENTS- Viruses to
tapeworms.
 5.IMMUNOLOGIC REACTIONS-
Ex:Anaphylaxis/ Autoimmune
reactions.

14.  6. GENETIC DERANGEMENTS-
Ex: congenital malformations- DOWN’S
SYNDROME.
 7. NUTRITIONAL IMBALANCES:
Ex: PEM & obesity.

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.

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”

27. C….. U…..in next class

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.

33. PATHOGENESIS OF FATTY LIVER

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.

35. FATTY LIVER - GROSS

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.

37. FATTY LIVER - LP

38. FATTY LIVER -HP

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.

46. THANK…..U.