Cellular Adaptations - Cell injury - pathology

cellular adaptatoins

1. Cellular adaptations
Dr M H SHARIFF
Professor
Dept. of Pathology

2. CELLULAR ADAPTATIONS ARE THOSE IN
WHICH NEW PHYSIOLOGIC & MORPHOLOGIC CHANGES
OCCUR IN RESPONSE TO EXCESSIVE PHYSIOLOGIC or
PATHOLOGIC STIMULI , BUT PRESERVING THE CELL
VIABILITY AND MODULATING ITS FUNCTIONS.

3. Adaptations
reversible changes in
•size,
•number,
•phenotype,
•metabolic activity, or
•functions of cells
in response to changes in their environment.

4. Adaptations
Change in size
Change in number of cells
Change into another type
of cell

5. DEFINITIONS :
Cellular adaptations
 Hypertrophy
 Hyperplasia
 Atrophy
 Metaplasia
Reversible injury
Irreversible injury
Cell death
 Necrosis
 Apoptosis

6. HYPERTROPHY

7. HYPERTROPHY
• an increase in the size of cells,
•results in an increase in the size of organ.
•No new cells, just larger cells.
•Occurs in cells that cannot divideOccurs in cells that cannot divide
•The increased size of the cells is due to the
synthesis of more structural components of
the cells.

8. Hypertrophy
•can be
Physiologic
Pathologic

9. caused by
Functional demand
 Hormonal
Compensatory

10. Examples: Physiological
•Skeletal muscles of Body buiders / weight lifters
•Uterus during pregnancy
•Lactating breast.

11. BODY BUILDING – MUSCLE HYPERTROPHY

12. HYPERTROPHY INCREASED
FUNCTIONAL DEMAND

13. HYPERTROPHY & INCREASED
FUNCTIONAL DEMAND
A
A
A = Normal heart
B
B
B = Hypertensive heart
C
C
C = Dilated heart

15. Examples: Pathological
•Chronic hemodynamic overload
•Cardiac enlargement –1.hypertensionCardiac enlargement –1.hypertension
- 2. aortic valve stenosis- 2. aortic valve stenosis
•Excessive hormonal stimulation :
Excess of estrogen → DUB
Excess of androgen → BPH

16. CARDIAC HYPERTROPHY
LV
MYOCARDIUM
R
V

18. Mechanisms of Hypertrophy

19. Mechanism
G
0  G
1
•↑ synthesis of growth factors.
•↑ transcription of genes.
•↑ cell proliferation.

20. HYPERPLASIA

21. Definition: Hyperplasia:
It is an increase in the size of tissue or organ
due to increase in the number of its cells.
Occurs in the cells capable of dividing
Although hyperplasia and hypertrophy are
distinct processes, frequently they occur
together,

22. Hyperplasia

•physiologic
•pathologic

23. Physiologic hyperplasia
•can be divided into:
(1) hormonal hyperplasia, which increases the
functional capacity of a tissue when needed, and
(2) compensatory hyperplasia,

24. Physiological hyperplasia
•Physiological hyperplasia of the breast in
pregnancy and lactation.
•proliferation of the glandular epithelium of
the female breast at puberty

25. Compensatory hyperplasia
•myth of Prometheus
•kidney / Lung due to removal of the other

26. Patholologic hyperplasia
1. Increased functional demand:
•Hyperplasia of the bone marrow in haemolytic
anaemia, Fe, B12 or folic acid deficiency
anaemias.
•Hyperplasia of the lining epithelia in the
process of regeneration and repair of an ulcer
or skin wounds.

27. 2. Increased hormonal stimulation
A) Hyperplasia of endocrine glands:
* Pituitary gland  excess growth hormone:
•Before puberty  gigantism.
• After puberty  acromegaly.
* Thyroid gland  thyrtoxicosis. * Parathyroid
gland  hypercalcaemia  metastatic
calcification  osteitis fibrosa cystica.
* Adrenal cortex  Cushing’s syndrome.

28. THYROID
HYPERFUNCTION
Exophthalmos

29. B) Hyperplasia of endocrine-target organs:
* Breast  mammary cystic hyperplasia
(Fibrocystic disease).
* Endometrium  endometrial hyperplasia.
* Prostate  senile nodular hyperplasia.
They result from increased oestrogenic stimulation.

30. ENDOMETRIAL HYPERPLASIA

31. Smooth muscles
The uterus in pregnancy.
Stomach in pyloric stenosis.
Alimentary tract proximal to an obstruction.
Urinary bladder with obstruction to urine
outflow e.g. prostatic enlargement or urethral
stricture.

32. With hypertrophy of the muscle wall

33. c) Cardiac muscle:
* Right ventricle: in MS, Tl, PS, chronic lung
diseases.

* Left ventricle in MI, AS, AI, systemic
hypertension.

34. MS
MI
RS Hypertrophy
LS Hypertrophy
Chronic lung diseases:
RSH hypertrophy

36. Mechanisms of Hyperplasia
•Hyperplasia is the result of growth factor–
driven proliferation of mature cells and, in
some cases, by increased output of new cells
from tissue stem cells

37. ATROPHY

38. atrophy
•Physiologic
•Pathologic

39. Physiological atrophy
Ductus arteriosus & umbilical vessels, after
birth.
Thymus gland after puberty.
Lymphoid tissue in adenoid and tonsils.
Postmenopausal atrophy of the breast, uterus and
ovaries.
Aging process in the skin,
brown atrophy of the heart & brain atrophy.
Postpartum involution of the uterus.

40. Blood supply Nerve Supply
Does A FunctionHormonal Stimulation

41. Mechanisms include:
1.Loss of innervation.
2.Reduced nutrient and oxygen supply.
3.Reduced functional demand.
4.Reduced hormonal stimulation.
These can occur under physiologic
or pathologic conditions.

42. Pathologic
1.Ischemic atrophy (↓ blood supply )
2.Disuse atrophy
3.Denervation atrophy
4.Pressure atrophy
5.Inadequate nutrition
6.↓ endocrine stimulation

43. Pathologic atrophy:
Ischaemic atrophy: usually due to partial and gradual occlusion
of the arterial blood supply by atherosclerosis, in the heart
(atherosclerotic heart disease), brain or kidney etc.
Disuse atrophy: due to forced inactivity of muscle e.g. after
prolonged immobilization of a limb in plaster Cast.
Neuropathic atrophy: due to lower motor neuron lesions e.g.
poliomyelitis.
Pressure atrophy upon a localized area or group of cells,
interfering with its blood and nutrient supply.
Pressure by growing tumour.
Prolonged pressure of a pulsating aortic aneurysm may cause pressure
atrophy of the undersurface of the sternum anteriorly or of the bodies of the
vertebrae posteriorly.
Excessive amyloid deposition in the liver sinusoids  atrophy of adjacent

44. Hormonal atrophy: cessation of pituitary activity
results in atrophic changes in the thyroid, adrenals,
ovaries and other organs that are influenced by
pituitary hormones.
Secondary to immunologic injuries: the resulting
tissue damage is accompanied by fibrosis and
atrophy of the affected organ e.g. primary
Addison’s disease due to autoimmune bilateral
atrophy of adrenal gland, atrophic gastritis, atrophic
thyroiditis, testicular atrophy, chronic diffuse
glomerulonephritis etc.

45. Mechanisms of Atrophy
•results from decreased protein synthesis and
increased protein degradation in cells.
•Protein synthesis decreases because of
reduced metabolic activity.
•The degradation of cellular proteins occurs
mainly by the ubiquitin-proteasome pathway.

46. Atrophy
A, Normal brain of a young adult.
B, Atrophy of the brain atherosclerotic cerebrovascular disease,

47. ATROPHY & ISCHEMIA
Renal atrophy Testicular atrophy

48. Gradual diminution in blood supply and nutrients
Lead to reduction in oxygen supply &cellular atrophy

50. STARVATION ATROPHY

51. ATROPHY & MALNUTRITION

52. PRESSURE ATROPHY

53. DISUSE MUSCLE ATROPHY

54. NEUROPATHIC ATROPHY
( POLIOMYELITIS )

55. ATROPHY & DECREASED TROPHIC
SIGNALS
Normal Endometrium Atrophic Endometrium

56. ATROPHY & CHRONIC
INFLAMMATION
Celiac SprueNormal Jejunum

57. METAPLASIA

58. Definition : Metaplasia
It is the transformation of one type of
differentiated tissue into another type of the
same kind.
occur in either epithelial or connective tissue.
It carries the risk of malignant transformation.

59. Pathogenesis:
Metaplasia is thought to arise from
reprogramming of stem cells to differentiate
along new pathway under the effects of
mixture of cytokines and growth factors.

61. A) Epitlielium metaplasia
1. Squamous metaplasia: 2. Columnar metaplasia

( 1) Squamous metaplasia
a) From pseudo-stratified columnar:
* Trachea and bronchi in chronic bronchitis, cigarette smoking
and bronchiectesis.
* Nasal sinuses in chronic sinusitis and hypovitaminosis A.
B) From transitional epithelium in bilharziasis of U.B.
c) From simple columnar epithelium:
* Endocervical mucosa and glands in cervical erosion.
* Gall bladder with stones.
d) From mesothelium of the pleura and peritoneum.

62. (2) Columnar metaplasia
(A) From squamous: in the lower oesophagus e.g.
Barrett oesophagitis (Precancerus).
(B) Intestinal metaplasia of the specialized gastric
mucosa in chronic atrophic gastritis.
(C) Apocrine, pink cell, hyperplasia seen in fibrocystic
disease of the breast.
(D) In mesothelium of pleura, peritoneum and
synovium.

64. Connective tissue metaplasia
•- It is the formation of cartilage, bone or adipose
tissue, in tissues that normally do not contain
these elements.
•Osseous metaplasia: occurs in:
(a) Sites of dystrophic calcification e.g. in scars, old
T.B.
(b) In muscles, in post-traumatic myositis ossificans.

65. Scar
Bone
Formation of bone in fibrous tissue
In case of healing of a wound

66. Hypoplasia
•is underdevelopment or incomplete
development of a tissue or organ.
•refers to an inadequate or below-normal
number of cells

67. Underdeveloped conditions
•Breasts during puberty tuberous breast
•Testes in Klinefelter's syndrome
•Ovaries in Fanconi anemia, gonadal dysgenesis,
trisomy X
•Labia majora in popliteal pterygium syndrome
•Cerebellum caused by mutation in the Reelin gene
•Chambers of the heart in hypoplastic left heart
syndrome and hypoplastic right heart syndrome
•Optic nerve in optic nerve hypoplasia
•Sacrum in sacral agenesis

68. •Facial muscle in asymmetric crying facies
•Lungs, often as a result of oligohydramnios
during gestation or the existence of
congenital diaphragmatic hernia
•Small bowel in Coeliac disease
•Fingers and ears in Harlequin type ichthyosis

69. Aplasia
•"defective development or congenital
absence of an organ or tissue.“
•In hematology, the term refers to
"incomplete, retarded, or defective
development, or cessation of the usual
regenerative process."

70. •Acquired pure red cell aplasia
•Aplasia cutis congenita
•Aplastic anemia
•Germ cell aplasia, also known as Sertoli cell-only
syndrome
•Radial aplasia
•Thymic aplasia, which is found in DiGeorge
syndrome and also occurs naturally as part of the
gradual loss of function of the immune system later
in life

71. Dysplasia
(Intraepithelial neoplasia)
Definition: It is partial loss of differentiation.
1. The involved epithelium shows evidence of cellular atypia:
Pleomorphism of cells (variation in size and shape).
Hyperchromatic nuclei with increased nucleo-cytoplasmic
ratio and increased mitotic activity.
Loss of polarity (orientation) of cells.
Disordered maturation with impaired function.
No invasion of basement membrane.
2. It represents reaction to underlying inflammation or to
chronic irritation.
3. Mild and moderate degrees of dysplasia are reversible when
the evoking stimulus is removed. However, severe degree is
considered pre-malignant.

73. A section of the uterine cervix shows neoplastic
squamous cells occupying the full thickness of the
epithelium and confined to the mucosa by the underlying
basement membrane.
Carcinoma in situ.

74. 4. Examples of dysplasia:
•1. Occurs in the cervix in chronic cervicitis.
•2. In urothelium of urinary bladder in case of
bilharziasis.
5. The most severe form, when the changes occupy the
whole thickness of the epithelium indicates the
diagnosis of intraepithelial carcinoma or carcinoma in
situ (pre-invasive carcinoma). Carcinoma in situ
characterized by diffuse cellular atypia involving the
whole thickness of the affected epithelium without
invasion of the basement membrane. The commonest
sites of IEN are cervix uetri, bronchial epithelium,
buccal mucosa and skin.