Basic pathology

Dr. Mishaal
Adaptations &
Accumulations
 Objectives
The students should:
- Understand the concept of cells and tissue adaptation to
environmental stress including the meaning & types of
hypertrophy, hyperplasia, atrophy, hypotrophy and
metaplasia with their clinical manifestations.
- Understand the causes of and pathologic changes
occurring in intracellular and extracellular
accumulations of materials causing degenerations.
- Understand the causes of and pathologic changes of
exogenous and endogenous pigments (e.g. carbon, silica,
iron, melanin, bilirubin and lipofuscin), Amyloidosis
definition and types, Calcification Definition and types
(Dystrophic Calcification & Metastatic Calcification)
Adaptations
 Cellular Responses
Stimulus Cellular Response
A) Altered Physiologic: Adaptations
Increased demand or stimulation Hyperplasia (increased number cells)
(eg., growth factors, hormones) Hypertrophy (increase size cells/organ)
Decreased nutrients or Hypoplasia (decreased number of cells)
stimulation Atrophy (decrease size cells/organ)
Chronic irritation (chemical, Metaplasia (reversible change from one
physical, inflammatory) adult cell type to another)
B) Injurious agents e.g. reduced Cell Injury
O2, infection, chemical toxins
Mild acute and self-limited Acute reversible injury
Progressive & severe Irreversible injury  cell death
(including DNA damage) (necrosis or apoptosis)
Mild chronic injury and Metabolic Alterations in organelles and Intracellular
alterations & extracellular accumulations
Cellular Responses
 Adaptation
• Def : Adaptation is reversible functional and structural
cell response to stress in which a new steady state is
achieved which allows the cell to survive and continue its
functions.
• Cells respond to modest changes (stress and injuries) by
functional and structural different types of adaptations.
• General causes of adaptations : Cells respond to
increased work demand and trophic stimulation by
hypertrophy or hyperplasia, and they respond to reduced
supply of nutrients and growth factors and reduced
stimulation by atrophy. In some situations, cells change
from one type to another, a process called metaplasia.
 Normal Growth & Maturation

• The cells continue to grow, divide (proliferate) and

mature (differentiate) to maintain the normal
structure of a particular tissue, adapt to modest
stimuli, and repair after injury.
 Normal Growth & Maturation
Tissue- proliferative activity

The type of cells according to heir proliferative activity

are divided into three groups:

1. Labile cells: Proliferate continuously e.g.: epithelial

cells, haemopoeitic and lymphoid tissue.
2. Stable cells: Repair in these cells occur by regeneration
or by fibrosis e.g.: parenchymal cells of liver, kidney
and pancreas, and mesenchymal cells as smooth
muscles, fibroblasts and osteoblasts.
3. Permanent cells: These cells do not regenerate e.g.:
neurons, skeletal muscles and heart muscles.
 Control of growth
• Cell proliferation - cell differentiation - cell death
• The growth of a tissue reflects the net balance of
cell proliferation and differentiation on the one
hand and cell death on the other.
• Rate of proliferation is determined by the
interplay of a variety of growth factors with their
corresponding receptors.
• Differentiation: is genetically programmed
development of cell into mature functional state,
demonstrated by specific morphologic features
 Molecular mechanisms of adaptation
Usually the process of adaptation occurs through these
main following steps :
• Receptor binding (up and down regulation)
• Signal transduction
• Transcription : DNA-directed synthesis of RNA
• Translation : messenger RNA-directed synthesis of
protein
• Regulation of protein (structural and functional
proteins) synthesis, packaging, and release, which result
in increased or decreased quantity of proteins in general
or production of specific types of proteins
Principle of signaling

12
Principle of signaling
 Adaptations
• Hyperplasia : Is the increase in the size of an organ or
tissue caused by an increase in the number of cells.

*Note: in order for cells to respond with this adaptation,

they must be capable of undergoing mitosis through
synthesis of DNA (capable of replication), i.e. either labile
cells or stable cells.

*Note: hypoplasia is not classified as adaptation, but it is a

developmental disorder. Hypoplasia is a decrease in the
number of cells in an organ or tissue, especially used for
congenital inadequate below-average number of cells in an
organ, or tissue that has not attained normal maturity.
 Types of Hyperplasia
• Physiologic hyperplasia
• Pathologic hyperplasia
 Types of Hyperplasia
Physiologic hyperplasia :
• Appropriate cellular proliferation to maintain normal
function
• Physiologic hyperplasia are of two types
- A- Hormonal hyperplasia e.g. the proliferation of the
glands of the female breast at puberty and during
pregnancy.
- B- Compensatory hyperplasia e.g. when a portion of
liver is partially resected, the remaining cells multiply
and restore the liver to its original weight.
 Hyperplasia:
Physiologic
Breast lobule, normal
25-year-old female

Breast lobule, 25-year-old

pregnant female: increase in
number of acini within lobule

25-year-old post-partum
female: secretory products in
apical cytoplasm of epithelial
cells;
what kind of secretion?
Apocrine (lactation)
Fig. 25-2, Pathologic Basis of Disease, 6th ed, WB Saunders, 1999.
 Types of Hyperplasia
Pathologic hyperplasia :
• Inappropriate cellular proliferation which goes
beyond range of normal function, possibly causing
signs or symptoms of disease.

• Examples: endometrial simple hyperplasia,

endometrial complex hyperplasia with atypia,
breast hyperplasia in fibrocystic disease, benign
prostatic hyperplasia
 Mechanism: pathologic hyperplasia
• Causes : most common are :
1- Excessive hormonal stimulation: e.g.,
• Endometrial hyperplasia:
– Increased Estrogen
– Progesterone/Estrogen imbalance
• Benign prostatic hyperplasia:
– Androgens

2- Excessive growth factor action on target cells : e.g.,

• Skin wart due to viral effect :
– Human Papilloma Virus ( HPV ) .
 Mechanism: pathologic hyperplasia
• Implications for disease
– While pathologic hyperplasia still responds to
regulatory control mechanisms, it can cause signs or
symptoms of disease, and create more opportunity for
acquired mutations that may lead to development of
neoplasia
• Is hyperplasia reversible???
– YES
• Is hyperplasia premalignant ?
– NO…..BUT…patient is at increased risk to develop
cancer, such as in Endometrial hyperplasia
Prostate Hyperplasia
Prostate Hyperplasia
ADRENAL HYPERPLASIA
 Endometrial Hyperplasia

Polipoid endometrium
 Endometrial Hyperplasia

Endometrium : Cystic endometrial hyperplasia

 Pathologic Hyperplasia: Application

Top--increased gland density (:Simple

Normal hyperplasia))
proliferative Bottom--increased gland density with complex
endometrium architecture & nuclear pleomorphism:
(Complex hyperplasia with atypia)
Endometrial carcinoma and endometrial hyperplasia
 Adaptations
• Hypertrophy : Is an increase in the size of the
tissue/organ due to the increase in the size of the
cells.

• Hypotrophy : decrease in size of cells (not commonly used term).

• Atrophy : decrease in size of cells, or an entire
organ(the commonly used term), after attaining its
normal mature growth
 Adaptations
• Hypertrophy : Is an increase in the size of the
tissue/organ due to the increase in the size of the
cells.
• *Note: Increased cell size is not due to cellular
swelling, but to synthesis of more structural
components especially intracellular proteins
 Types of Hypertrophy
• Physiologic
– Physiological hypertrophy of lactating breast
– Massive growth of uterus in pregnancy (hypertrophy
and hyperplasia, but mainly hypertrophy of smooth
muscles) mediated by estrogen
– Skeletal muscles of athletes (increased exercise
Increased metabolic demand The cells increase in
size.
• Pathologic
– Cardiac concentric left ventricular hypertrophy due to
chronic hemodynamic overload (increased work
demand); observed in chronic uncontrolled
hypertension
Physiologic Hypertrophy
Pathologic Hypertrophy
Left ventricular hypertrophy
 Pathologic Hypertrophy
A
B

NORMAL
(350 grams)
A- 55 y.o. male with 15 year B- 70 y.o. male with 40 yr.
history of essential history of essential hypertension,
hypertension, can play tennis short of breath walking up 10
without shortness of breath, steps at home; heart weighs 600
heart weighs 550 grams? grams ? Dilation and
Concentric left ventricular hypertrophy (longer
hypertrophy (non-dilated) duration hypertension)
 Cardiac hypertrophy in hemodynamic overload

Fig. 1-4, Pathologic Basis of Disease, 2005

What are signals that trigger
cardiac myocyte hypertrophy
and changes in gene expression?
Mechanical: stretch of fibers
Trophic: peptide growth factors,
vasoactive agents that increase nutrients
for growth of cells
 Hypertrophy and hyperplasia
• Hypertrophy and hyperplasia can occur
together, e.g.
– the uterus during pregnancy in which there
is smooth muscle hypertrophy and
hyperplasia.
– Lactating breast
– Benign prostatic hyperplasia
 Adaptations
• Atrophy: decrease in size of cells, tissue or an
entire organ after attaining its normal mature
growth.
• Partial or complete wasting away or progressive
decline of a part of the body (tissue or an organ)
• In atrophy both the number and size of cells are
decreased
 Adaptations: Atrophy
• In medical practice, hormonal and nerve inputs that
maintain an organ or body part are said to have trophic
effects. A diminished muscular trophic condition is
designated as atrophy. Atrophy is reduction in size of cell,
organ or tissue, after attaining its normal mature growth.
• Origin of term: Late 16th century: from French atrophier
(verb), atrophie (noun), from late Latin atrophia, from
Greek, ‘lack of food’, from a- ‘without’ + trophē ‘food’. Or
"lack of nourishment". Although the English word doesn't
usually imply any lack of food, it always refers to a wasting
away
 Types of atrophy stimuli
Mechanisms and causes: Atrophy may be due to :
• Physiologic stimuli : e.g. the loss of hormone
stimulation in menopause (Loss of endocrine
stimulation : atrophy of uterus and breasts in
post-menopausal female)
• Pathologic stimuli : e.g. the loss of denervation,
mild chronic ischemia, pressure, disuse, etc...
• Aging : atrophy of permanent cells in brain and
heart in 80 year old person (senile atrophy).
 Pathologic causes of atrophy
• Disuse : loss of skeletal muscle mass with arm in
cast for 6 weeks
• Denervation : traumatic damage to nerve 
atrophy of muscle fibers supplied
• Ischaemia : unilateral atrophy of one kidney due to
renal artery stenosis
• Inadequate nutrition.
• Pressure atrophy.
• Excessive apoptosis of cells, or tissue intrinsic
disease.
 Adaptations: Atrophy
• Mechanisms of atrophy: Consist of :
- Combination of decreased protein synthesis and
increased protein degradation by ubiquitin protease
pathway
- Increased autophagy by forming autophagy vacuoles

Organ or tissue atrophy may be irreversible if

permanent cells undergo death by apoptosis
Normal
Atrophy - testis
 Small intestine / atrophy of villi

Normal Atrophy
Alzheimer disease – brain atrophy
Slide 2.5 W.B. Saunders Company items and derived items Copyright (c) 1999 by W.B. Saunders Company
Pathologic atrophy
 Adaptations
• Metaplasia definition : Reversible change in
which one mature cell type (epithelial or
mesenchymal) is replaced by another mature cell
type; typically the new cell type is better able to
withstand a chronic adverse environment.
• Vitamin A deficiency or excess both can cause
metaplasia.
• Vitamin A deficiency and cigarette smoking
induces squamous metaplasia in respiratory
epithelium.
 Metaplasia
• Mechanism: reprogramming of stem cells in basal layer
of epithelium or of pluripotent mesenchymal cells in
connective tissue, causing them to differentiate along a
new pathway.
• Metaplasia is usually reversible provided the causative
agent is removed.
• Persistent stimuli can initiate malignant transformation in
metaplastic epithelium such as squamous metaplasia in
respiratory epithelium leading to lung squamous cell
carcinoma, and squamous metaplasia in the bladder due
chronic irritation of schistosoma haematobium eggs
leading to bladder squamous cell carcinoma
 Metaplasia
• Types of metaplasia according to affected
tissue type:
• Epithelial metaplasia
• Mesenchymal metaplasia
 Adaptations: Metaplasia
Epithelial metaplasia :
• Squamous metaplasia (multiple sites ; bronchus,
endocervix, urinary bladder)
• Intestinal columnar metaplasia (esophagus,
stomach etc…)
• Gastric columnar metaplasia (esophagus,
intestine)
• Serous or mucinous metaplasia (germinal
epithelium of ovary)
 Adaptations: Metaplasia
Mesenchymal metaplasia :
• Osseous metaplasia (fibrous scars, areas of
calcification)
• Chondroid metaplasia
• Myeloid metaplasia
 Metaplasia
• Some important examples include:
1.Squamous metaplasia:
2.Columnar cell metaplasia
3.Osseous metaplasia
4.Myeloid metaplasia
 Squamous metaplasia
• Here columnar cells are replaced by squamous cells. e.g.
- In cervix: replacement occurs at the squamoc-olumnar junction.
Squamous cell carcinoma of cervix usually arises from the
squamous metaplasia in the cervix.
- In respiratory tract: the columnar epithelium of the bronchus is
replaced by squamous cell following chronic injury in chronic
smokers. The squamous epithelium is able to survive under
circumstances that the more fragile columnar epithelium would
not tolerate. Although the metaplastic squamous epithelium will
survive better, the important protective functions of columnar
epithelium are lost, such as mucus secretion and ciliary action. If
the causative agent persists, it may predispose to malignant
transformation. It is thought that cigarette smoking initially
causes squamous metaplasia, and later squamous cell cancers
arise from it.
 Columnar, osseous and myeloid metaplasia
2) Columnar cell metaplasia: it is the replacement of the
squamous lining by columnar cells. It is seen in the esophagus in
chronic gastro-esophageal reflux disease. The normal stratified
squamous epithelium of the lower esophagus undergoes
metaplastic transformation to columnar epithelium. This change
is called as Barrett’s oesophagus and it can be precancerous and
lead to development of adenocarcinoma of esophagus.

3) Osseous metaplasia: it is the formation of new bone at sites of

tissue injury.

4) Myeloid metaplasia (extramedullary hematopoiesis): is the

proliferation of hematopoietic tissue in sites other then the bone
marrow such as liver or spleen.
Metaplasia
Metaplasia
 Metaplasia
Clinical significance;
• Most metaplasia is of little significance.
• Functional deficits may result in some areas.
• Dysplastic changes with progression to cancer
can occur in metaplastic epithelium.
Metaplasia: Applications

Normal endocervical
mucosa
23 year old female with
chronic inflammation of
endocervical mucosa:
(Squamous metaplasia)

Cervical biopsy, 5 years after

infection with HPV type 16 or
18: Squamous carcinoma-in-
situ (CIN III, cervical
intraepithelial neoplasia III)
 Definitions
plasia and -trophy
•Hyperplasia (proliferation of cells)
•Aplasia (organ or part of organ missing)
•Hypoplasia (congenital below-average number of cells, especially when inadequate)
•Metaplasia (conversion in cell type)
•Prosoplasia (development of new cell function)
•Desmoplasia (connective tissue growth)
•Dysplasia (change in cell or tissue phenotype)
•Anaplasia (structural differentiation loss within a cell or group of cells)
•Neoplasia (abnormal proliferation)

•Atrophy (reduced functionality of an organ, with decrease in the

number or volume of cells)
•Hypertrophy (increase in the volume of cells)
•Hypotrophy (decrease in the volume of cells)
•Abiotrophy (loss in vitality of organ or tissue)
•Dystrophy (any degenerative disorder resulting from improper or faulty nutrition)
•THANKS