MEDICAL COUNCIL OF INDIA, COMPETENCY BASED UNDERGRADUATE CURRICULUM FOR THE INDIAN MEDICAL GRADUATE, 2018

1. PA 2.6
DESCRIBE & DISCUSS
CELLULAR ADAPTATIONS
ATROPHY, HYPERTROPHY,
HYPERPLASIA, METAPLASIA,
DYSPLASIA
Dr IRA BHARADWAJ
MCI TEACHER ID: PAT 2300569
KUHS FACULTY ID: M21512

2. TEXTBOOK REFRENCES
• ROBBINS BASIC PATHOLOGY
• HARSH MOHAN TEXTBOOK OF PATHOLOGY
• OTHER STANDARD REFRENCES

3. SLO
• DEFINITION OF ADAPTATION
• TYPES OF ADAPTATIONS
• ATROPHY
• HYPERTROPHY
• HYPERPLASIA
• METAPLASIA
• RELATED CONDITIONS
• DYSPLASIA
• REVISION WITH QUIZ

4. ADAPTATION
DEFINITION
Adaptation is a reversible change in
• size,
• number,
• phenotype,
• metabolic activity, or function of cell
in response to physiological changes or mild
injurious agents in their micro environment
resulting in new steady state preserving
structure and function of the cell.

5. ADAPTATIONS
TYPES
Various types of adaptations are -
• CHANGE IN SIZE OF CELLS - ATROPHY &
HYPERTROPHY –affect all types of cells eg labile,
stable & permanent cells
• CHANGE IN NUMBER OF CELLS - HYPERPLASIA –
affects only labile & stable cells
• CHANGE IN PHENOTYPE - METAPLASIA – affects
only labile & stable cells

6. ATROPHY
DEFINITION – decrease in cell size, may lead to
decreased organ size , depending on number of
cells affected
ETIOLOGY [CAUSE]
PHYSIOLOGICAL- (ka involution )
• notochord
• thyroglossal duct
• Many other embryonic / fetal structures
during embryogenesis or shortly after birth

7. ATROPHY
PATHOLOGICAL-
decrease in
• nutrition,
• blood flow,
• neural stimulation,
• hormones,
• work load
increase in external pressure

8. ATROPHY
PATHOGENESIS-
• Decrease in protein synthesis,
• Increase in protein degradation
(ubiquitin –proteasome)
• Autophagy

9. ATROPHY
AUTOPHAGY
• It refers to lysosomal digestion of cell’s own
components
• Survival mechanism of starved cells to
recycle cell contents for nutrition & energy
• Multiprotein complex initiates formation of
autophagic vacuole (autophagosome) near
SER, which fuses with lysosome to form
phagolysosome, digested material is
released for cellular recycling

10. ATROPHY
AUTOPHAGY
PHYSIOLOGICAL CAUSES
• Starvation Leading to atrophy followed
by cell death
• Seen in turnover of organelles
• Aging process

11. ATROPHY
AUTOPHAGY
PATHOLOGICAL CAUSES
• For clearing misfolded proteins in the cells, eg,
neurodegenerative disorders – Alzheimer,
Huntington
• Infectious organisms like mycobacteria,
shigella, HSV 1,
• Inflammatory bowel disease
• Cancer

12. ATROPHY
C/F & PROGNOSIS-
• Decrease in size of cells & organs,
• Decrease function of cell & organ
• Withdrawal of initiating cause is followed
by recover to normal
• Persistence of cause leads to cell death

13. HYPERTROPHY
DEFINITION – increase in size of cell
ETIOLOGY -
PHYSIOLOGICAL
• Increased workload (workout)
• Hormonal (pregnancy)
PATHOOGICAL
• Increased workload (hypertension)

14. HYPERTROPHY
PATHOGENESIS
• mechanical stretch,
• increase in growth factors & adrenergic
hormones
• increased protein synthesis,
• change to fetal or neonatal type eg,
alpha myosin of adult muscle replaced by
beta myosin as it is more energy efficient

15. HYPERTROPHY
MORPHOLOGY- increase size of cell &
organ, increase protein in each cell
CLINICAL FEATURES & PROGNOSIS –
• increase work done per cell,
• return to normal if stimulus is
withdrawn,
• degenerative changes or cell injury
occurs if cause persists

16. PHYSIOLOGICAL HYPERTROPHY
UTERUS: NORMAL & IN PREGNANCY

17. PATHOLOGICAL HYPERTROPHY
CARDIAC TISSUE: NORMAL & IN HYPERTENSION
IN-CREASE IN SIZE OF CELLS

18. HYPERPLASIA
DEFINITION- increase in number of cells by
proliferation of cells [labile or stable]
ETIOLOGY
PHYSIOLOGICAL
• Hormonal eg lactation,
• Compensatory, following loss of tissue eg
nephrectomy

19. HYPERPLASIA
PATHOLOGICAL
• Excess hormones
• Excess growth factors,
• Some viral infections
PATHOGENESIS- growth factors are
increased leading to increase in mitotic
activity of cell

20. HYPERPLASIA
MORPHOLOGY-
• Associated hypertrophy is usually
present
• Increase in number of cells & size of cells
• Increase in size of organ if sufficient
number of cells are affected

21. HYPERPLASIA
C/F & PROGNOSIS-
• Increase number of cells leads to
increase work done by the organ
• Returns to normal on withdrawal of
stimulus,
• If cause & increased mitotic activity
persist; it increases chances of
mutations & may lead to dysplasia &
neoplasia.

22. The normal microscopic appearance of female breast
tissue is shown here. There is a larger duct to the
right and lobules to the left. A collagenous stroma
extends between the structures. A variable amount
of adipose tissue can be admixed with these
elements.

23. The female breast during pregnancy undergoes
lobular hypertrophy & hyperplasia so that
following birth lactation can occur. Seen here are
lobules filled with pink secretions. The breast,
which histologically is a modified sweat gland,
secretes by budding off portions of cell cytoplasm.

24. These breast ducts demonstrate
pathological epithelial hyperplasia. The
epithelial cells are multilayered. There
is no atypia. Thus, there is no increased
risk for carcinoma

25. More florid ductal pathological epithelial
hyperplasia with dysplasia of the breast is
shown here. There is a slightly increased risk
(1.5 to 2 times normal) for breast carcinoma
when such changes are present.

26. ADRENAL GLAND SHOWING ATROPHY
NORMAL SIZE
HYPERTROPHY & HYPERPLASIA

27. METAPLASIA
DEFINITION- reversible change of one type of
adult cell to other type of adult cell [seen in
epithelial (labile) & stable cells]
ETIOLOGY-always pathological-
• Chemicals -tobacco smoke, GI secretions in
inappropriate site eg gastric secretions in
esophagus
• Mechanical – calculi eg in gall bladder &
bladder

28. METAPLASIA
• Vitamin A deficiency,
• Chronic infection eg H pylori
PATHOGENESIS-
• Reprogramming of stem cells to
differentiate to cells better able to
withstand stress
• Accompanied by loss of specialized
cellular function

29. METAPLASIA
MORPHOLOGY-
• Ciliated columnar cells in bronchus
change to squamous cells due to tobacco
smoke
• Squamous epithelium in esophagus
changes to intestinal/gastric type due to
reflux of gastric secretions

30. METAPLASIA
MORPHOLOGY-
• Transitional urothelium of bladder
changes to squamous epithelium due to
mechanical trauma of calculus
• mesenchymal tissues also show features
of metaplasia, though less commonly
than epithelial tissues, eg fibrous tissue
may change to bony tissue, following
repeated mild trauma

31. METAPLASIA
C/F & PROGNOSIS-
• Loss of normal function with survival
advantage eg loss of ciliary function in
bronchial mucosa
• Returns to normal on withdrawal of stimulus
• Increase in incidence of malignancy
[premalignant change]

32. SQUAMOUS METAPLASIA IN
BRONCHUS

33. Metaplasia of laryngeal respiratory epithelium has
occurred in a smoker. The chronic irritation has led to
an exchanging of one type of epithelium the normal
respiratory epithelium for another, the more resilient
squamous epithelium. Metaplasia is not a normal
physiologic process and may be the first step toward
neoplasia [premalignant change]

34. RELATED TERMINOLOGY &
CONDITIONS
• DYSPLASIA [discussed in detail]
• HYPOLASIA/AGENESIS [decreased/absence of
formation of structure]
• MALFORMATION [ill formed structure]

35. DYSPLASIA
• Dysplasia also ka atypical hyperplasia is a
growth disorder, usually occurring in
background of hyperplasia & metaplasia
• Dysplasia is a growth disorder, characterized
by loss of uniformity of cells & loss of normal
cellular architecture
• It usually affects the epithelium

36. DYSPLASIA
ETIOLOGY - Chronic inflammation due to any cause
• Chemical - smoking
• Infection – Human Papilloma Virus
• Mechanical - calculi
PATHOGENESIS
Changes in basal cells, which promote mitosis with
decrease differentiation & maturation of cells

37. DYSPLASIA
MORPHOLOGY OF NORMAL EPITHELIUM
• Only basal layer shows mitosis
• Upper layers show features of maturation &
differentiation, with orderly arrangement of cells
• Top layer is that of mature keratinized cells

38. DYSPLASIA
MORPHOLOGY OF DYSPLASTIC EPITHELIUM
• Increased number of layers of epithelial cells
• There is disorientation of cells, the cells are
not arranged in orderly layers eg individual
cells in middle layers may show keratinization
• There is increased mitosis in basal layer

39. DYSPLASIA
MORPHOLOGY OF DYSPLASTIC EPITHELIUM
[continued]
• Cells in upper layers also show mitotic activity
• Pleomorphic cells (variation in size & shape) are
present in all layers of cells
• Hyperchromatic nuclei (large deeply staining
nuclei) are evident in many cells in all layers

40. DYSPLASIA
CLASSIFICATION OF DYSPLASIA:
• MILD dysplasia – affects lower 1/3 of epithelium
• MODERATE dysplasia– affects 2/3 of epithelium
• SEVERE dysplasia also known as carcinoma in situ
( CA-IN-SITU ) – affects all layers of epithelium,
however basement membrane is intact & there is
no invasion

41. NORMAL CERVICAL EPITHELIUM
SQUAMOUS EPITHELIUM OF ECTOCERVIX
COLUMNAR EPITHELIUM OF ENDOCERVIX
& JUNCTION OF ENDO & ECTO CERVIX

42. MODERATE DYSPLASIA

43. MODERATE DYSPLASIA
Dysplastic basal cells occupy the lower two
thirds of the epithelium, characterized by:
• cuboidal shape,
• high nuclear cytoplasmic ratio,
• hyperchromatism,
• mitotic activity, and
• some loss of orientation to the basement
membrane

44. CARCINOMA IN SITU
(SEVERE DYSPLASIA)

45. CARCINOMA IN SITU
( SEVERE DYSPLASIA)
• This section shows that the dysplastic basaloid
cells go all the way to the surface
• They never undergo significant differentiation
towards more differentiated flattened
squamous cells.
• Note however that the basement membrane
is still intact.

46. DYSPLASIA
CLINICAL FEATURES
• Dysplasia's are usually asymptomatic or may present
with non specific symptoms
CLINICAL APPLICATION
• It is widely used as a screening tool for neoplasia ,
especially in uterine cervix, a common site for
malignancy, by technique of cytology [pap smear]
PROGNOSIS
• It is reversible in the early, mild & moderate stages
• The later severe stage, if untreated, may progress to
invasive Ca

47. QUIZ 1
ONE OF THESE IS NOT A FEATURE OF
ADAPTATION:
• IRREVERSIBLE CHANGE
• CHANGE IN CELL STRUCTURE
• CHANGE IN CELL FUNCTION
• NEW STEADY STATE

48. QUIZ 2
WHICH OF THESE IS NOT AN ADAPTATION:
• HYPERPLASIA
• METAPLASIA
• HYPOPLASIA
• HYPERTROPHY

49. QUIZ 3
AUTOPHAGY IS:
• INGESTION OF SELF CELLS
• INGESTION OF CELLULAR ORGANELLES
• INGESTION OF INTRA CELLULAR
MULTIPROTEIN COMPLEXES
• PROCESS OF CELL DEATH

50. QUIZ 4
HYPERTROPHY AFFECTS:
• STABLE CELLS
• LABILE CELLS
• PERMANENT CELLS
• ALL OF THE ABOVE

51. QUIZ 5
REPLACEMENT OF COLUMNAR EPITHELIUM TO
SQUAMOUS EPITHELIUM IN SMOKERS IS:
• HYPOPLASIA
• METAPLASIA
• HYPERPLASIA
• DYSPLASIA

52. QUIZ 6
WHICH CONDITION HAS THE MAXIMUM
POTENTIAL FOR MALIGNANCY [CANCER]:
• HYPERPLASIA
• HYPERTROPHY
• METAPLASIA
• DYSPLASIA