disturbance of growth by Prof.soheir saad

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DISTURBANCES OF GROWTH
CELLULAR ADAPTATION
BY DR.SOHEIR SAAD
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Overview
Stress
Normal cell
Adapted Cell
- Stress
Stress
Injury
- Stress
Reversibly injured cell
Apoptosis
Irreversibly Injured cell
Dead cell
Necrosis
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Cellular Reaction Pattern To Stress Depends On

• 1.Type, duration, and severity of
• stress.
• 2. Type, state and adaptability of
• cell.

I-Irreversible Cell Injury Severe stimuli leads
to necrosis . Apoptosis II-Reversible Cell
Injury Mild stress for short duration leads to
biochemical change or mild form of morphologic
change in the affected cells ( hydropic swelling).
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III-Persistent prelethal stress leads to cellular
adaptation.

• 1-Adaptation of growth.
• a) Increased growth and cellular activity e.
  g.Hypertrophy Hyperplasia
• b) Decreased growth and cellular activity e.g.
  Atrophy.
• 2-Disturbances of cellular differentiation and
  morphology e.g. Metaplasia, Dysplasia.
• 3-Intra and Extra cellular accumulations e. g.
• a) Lipids as in fatty change Cholesterol
  deposits.
• b) Proteins as in Hyaline change Amyloidosis.
• c) Pigments as in Pathologic pigmentation.
• d) Calcium as in Pathologic Calcification
• e) Enzymatic metabolic deficiency as in Gout
  lyzosomal storage disease.

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DISTURBANCES OF GROWTHDuring intrauterine Life

• Agenesis Complete absence of an organ e.g.,
  kidney.
• Aplasia The organ is rudimentary is formed
  of cells resembling its embryonic origin e.g.,
  kidney.
• Hypoplasia Failure to reach full-sized
  develop-ment e.g., infantile uterus .
• Hamartoma ?????
• Teratoma ???????

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CELLULAR ADAPTATION
DIFINITION

• Cellular adaptation is a state that lies
  intermediate between the normal unstressed cell
  and the injured over stressed cells.
• The major most important adaptive changes in the
  cells are
• 1. Atrophy,
• 2. Hypertrophy,
• 3. Hyperplasia
• 4.Metaplasia,
• 5.Dysplasia and intracellular storage.

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ATROPHY

• Definition

• It is reduction in the size of an organ after it
  has reached normal adult development, due to
  decrease in the number and/or the size of its
  specialized cells. Atrophy represents a reduction
  in the structural component of the cell.

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ATROPHY

• Atrophy may progress to the point at which cells
  are injured and die and replaced by fatty in
  growth.

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Blood supply
Nerve Supply
Hormonal Stimulation
Does A Function
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• Mechanisms include
• Loss of innervation.
• Reduced nutrient and oxygen supply.
• Reduced functional demand.
• Reduced hormonal stimulation.
• These can occur under physiologic or pathologic
  conditions.

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A) Physiological Atrophy

• Ductus arteriosus and 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 and brain atrophy.
• Postpartum involution of the uterus.

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B) 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 following lower motor neuron
  lesions e.g. poliomyelitis.

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• 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

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Gradual diminution in blood supply and
nutrients Lead to reduction in
oxygen supply cellular atrophy
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• 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 Addisons disease due to autoimmune
  bilateral atrophy of adrenal gland, atrophic
  gastritis, atrophic thyroiditis, testicular
  atrophy, chronic diffuse glomerulonephritis etc.

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HYPERTROPHY

• DIFINITION

It is the increase in the size of the organ or
tissue due to increase in the size of it
specialized cells
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In a pure form, it is found in muscles1. Occurs
in response to an increased demand for overwork

• Physiological Hypertrophy
• Skeletal muscle in athelets
• Smooth muscle The uterus in pregnancy.
• Pathologoical Hypertrophy
• Smooth muscles
• Stomach in pyloric stenosis.
• Alimentary tract proximal to an obstruction.
• Urinary bladder with obstruction to urine outflow
  e.g. prostatic enlargement or urethral stricture.

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With Hypertrophy Of The Muscle Wall
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• Cardiac muscle
• Right ventricle in MS, Tl, PS, chronic lung
  diseases.
• Left ventricle in MI, AS, AI, systemic
  hypertension.

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Chronic lung diseases
RS Hypertrophy
MS
MI
RSH hypertrophy
LS Hypertrophy
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LVH in Chronic Hypertension
Left Ventricular Hypertrophy
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• 2. Physiologic (hormonal) hypertrophy occurs
  during maturation under the effects of hormones.
  Sex hormones at puterty lead to hypertrophy of
  juvenile sex organs, and breast tissue in
  lactating women under the effect of prolactin.
• 3. Compensatory hypertrophy of one kidney due to
  removal of the other

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HYPERPLASIA

• Definition
• It is an increase in the size of tissue or organ
  due to increase in the number of its specialized
  cells.

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HYPERPLASIA

• 1. Increased functional demand
• 2. Increased hormonal stimulation
• A)Hyperplasia of endocrine glands
• B) Hyperplasia of endocrine-target organs
• 3. Chronic inflammation or irritation
• 4. Hyperplasia of connective tissue
• 5. Compensatory hyperplasia
• 6. Pseudoneoplastic hyperplasia

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HYPERPLASIA

• Can result from
• 1. Increased functional demand
• Physiological hyperplasia of the breast in
  pregnancy and lactation.
• 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.

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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 ? Cushings syndrome.

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THYROID HYPERFUNCTION
Exophthalmos
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• 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.

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ENDOMETRIAL HYPERPLASIA
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HYPERPLASIA OF ENDOCRIN TARGET ORGAN
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3. Chronic inflammation or irritation

• Pressure from ill fitting shoes causes
  hyperplasia of the skin (calluses).
• Chronic cystitis of the bladder commonly causes
  hyperplasia of the bladder epithelium
  (Bilharziasis stones).
• Chronic inflammatory lesions of the skin ?
  hyperplasia.

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• 4. Hyperplasia of connective
• tissue cells in wound healing (proliferating
  fibroblasts and blood vessels.
• 5. Compensatory hyperplasia in the liver after
  partial hepatectomy.

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6. Pseudoneoplastic hyperplasia

• a) Pseudomalignant connective tissue hyperplasia
  e.g. pseudolymphoma of the orbit and
  pseudosarcoma in fibrous tissue.
• b) Pseudomalignant epithelial hyperplasia e.g.
  keratoacanthoma and hyperplasia of the skin
  around chronic ulcer.
• b) It is also controlled by growth inhibitors
  e.g. TGF-B and others.

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Cell proliferation depends on the action of

• a) Some growth factors and cytokines e.g.
  epidermal growth factor (EGF)-alfa transforming
  growth factor (TGF-?), Her- 2 neu-and
  interleukin-6 (IL-6) and tumour necrosis factor
  (TNF-?).
• b) It is also controlled by growth inhibitors
  e.g. TGF-B and others.

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It Differs From Neoplasia By The Following

• It occurs in tissue made up of labile or stable
  cells that have the power of regeneration under
  normal or pathologic conditions.
• Occurs in response to a stimulus, continues as
  the stimulus continues and disappears when it is
  removed.
• Usually performs a function e.g. Lactating
  breast.
• It is a reversible non-neoplastic process,
  nevertheless sometimes malignant tumours do arise
  on top of abnormal or atypical hyperplasia
  (Endometrial hypeplasia).

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METAPLASIA
Definition

• It is the transformation of one type of
  differentiated tissue into another type of the
  same kind. It may occur in either epithelial or
  connective tissue.
• 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.
• The most common is the replacement of a glandular
  epithelium by a squamous one due to prolonged
  chronic irritation, replacing the thin delicate
  epithelium with the tougher and more resistant
  squamous epithelium.
• It carries the risk of malignant transformation.

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• 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.

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(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.

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• Metaplasia of esophageal squamous mucosa has
  occurred here, with gastric type columnar mucosa
  at the left.

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(B) 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.

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

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• 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.

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Carcinoma in situ.
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.
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• DYSPLASIA.
• The normal squamous epithelium at the left
  transforms to a disorderly growth pattern at the
  right. This is farther down the road toward
  neoplasia.

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• 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.

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