CELLULAR ADAPTATION AND

INTRACELLULAR ACCUMULATION

Dr. Cahyono Kaelan, PhD

Kinds of human cells
REGULATION & CELL GROWTH
 If there are wound, necrosis and damage of the
cells, the rest of the cell will proliferate and
restore the cells through:

 REGENERATION
 REPAIR
3 group of cells according capacity
to regenerate in physiologcal
condition

 1. Labile cells
 2.Stable cells
 3. Permanent cells
LABILE CELLS
 Continuos process of active replacement.
 Regeneration is very active

 Covering epithelium (external and

internal)
 Bone marrow cells

 Lymphoid cells
STABLE CELLS
 Potential replacement is minimal but good
response to damage.

 Liver
 Endocrin glands

 Renal tubular epithelium

PERMANENT CELLS
 Normaly minimal or unable to multiply
after the growth phase in early life
 Can not regenerate and healing by
granulation tissue with permanent loss of
function .
 Nerve cells
CELL CYCLE

G0-G1-S-G2-M

S: Synthesis
M: Mitosis
The adaptive changes in cell growth
and differentiation that are:
 atrophy (decrease in cell size),
 hypertrophy (increase in cell size),
 hyperplasia (increase in cell
number), and
 metaplasia (change in cell type).
 1. ATROPHY
 Atrophy Is an Adaptation to Diminished Need or
Resources for a Cell's Activities.
 Shrinkage in the size of the cell by the loss of cell
substance
 Atrophy may result from disuse of skeletal muscle
or from loss of trophic signals as part of normal
aging.
 Atrophyc cells is remaining viable.
It may occur under both pathologic
and physiologic circumstances
 Physiologic (e.g., the loss of hormone
stimulation in menopause)
 Pathologic (e.g., denervation),

Althoug different the fundamental cellular

changes are identical.
They represent a retreat by the cell to a smaller
size at which survival is still possible
 Atrophy occurs under a variety of
conditions outlined below:
 a decreased workload
 (for example, immobilization of a limb to permit

healing of a fracture, after prolonged bed rest),

 a loss of innervation,
 neurologic damage, poliomyelitis or traumatic

spinal cord injury, leads to denervation of

muscle
 a diminished blood supply,
 It is frequently seen in the heart, brain, and

kidneys following vascular occlusion in these

organs.

 inadequate nutrition,
 Starvation or inadequate nutrition associated

with chronic disease leads to cell atrophy,

particularly in skeletal muscle
 a loss of endocrine stimulation,
 The functions of many cells depend on signals transmitted

by chemical mediators and the endocrine system.

 loss of thyroid-stimulating hormone (TSH),

adrenocorticotropic hormone (ACTH, also termed

corticotropin), and follicle-stimulating hormone (FSH)
results in atrophy of the thyroid, adrenal cortex, and
ovaries, respectively.
 Persistent Cell Injury
 Persistent cell injury is most commonly

caused by chronic inflammation

associated with prolonged viral or
bacterial infections.
 The atrophy of the gastric mucosa that

occurs in association with chronic gastritis

 Aging
 One of the hallmarks of aging, particularly
in nonreplicating cells such as those of the
brain and heart, is cell atrophy.
 The size of all parenchymal organs
decreases with age.
 the term senile atrophy has been used.
A, Atrophy of the brain in an 82-year-old man. The
meninges have been stripped. B, Normal brain of a
25-year-old man, for comparison.
the mechanisms of cell atrophy
 Decrease protein synthesis
 Decrease gene expression
 Decrease signaling
 Decrease energy utilization
 Increase protein degradation
2. HYPERTROPHY
 Hypertrophy is an increase in the size of
cells and consequently an increase in the
size of the organ.
 In pure hypertrophy, there are no new cells,
just bigger cells, enlarged by an increased
synthesis of structural proteins and
organelles.
 In organs made of permanent cells/ non dividing cells (e.g.,
heart, skeletal muscle), adaptive responses are accomplished
by increased cell size. In other organs (e.g., kidney, thyroid)
cell numbers and cell size may both increase.
 Hypertrophy can be physiologic or pathologic and is caused
either by increased functional demand or by specific
hormonal stimulation.
 Hypertrophy and hyperplasia can also occur together, and
obviously both result in an enlarged organ.
 Physiologic hypertrophy of the uterus during pregnancy
occurs as a consequence of estrogen stimulation of both
smooth muscle hypertrophy and smooth muscle
hyperplasia.
 Weight lifter can develop his or her rippled physique
only by hypertrophy of individual skeletal muscle cells
induced by an increased workload.
 Pathologic cellular hypertrophy include the cardiac
enlargement due to hypertension or aortic valve disease .
Physiologic hypertrophy of the uterus during pregnancy.
Gross appearance of a normal uterus (right) and a gravid
uterus (left) that was removed for postpartum bleeding
There is marked left ventricular hypertrophy, with
asymmetric bulging of a very large interventricular septum
into the left ventricular chamber
 3. HYPERPLASIA
 Hyperplasia is an increase in the number of
cells in an organ or tissue.
 The specific stimuli that induce hyperplasia
and the mechanisms by which they act vary
greatly.
 Hyperplasia involves stimulating resting (G0)
cells to enter the cell cycle (G1).
 Physiologic hyperplasia is divided into:

(1) hormonal hyperplasia,

 Proliferation of the glandular epithelium of the female breast at

puberty and during pregnancy

(2) compensatory hyperplasia,
 Hyperplasia that occurs when a portion of the tissue is removed

or diseased. For example, when a liver is partially resected,

 Hyperplasia of connective tissue cells in wound healing
 Pathologic hyperplasia
 Due to excessive hormonal or growth factor stimulation.
 For example, if the balance between estrogen and

progesterone is disturbed, endometrial hyperplasia

ensues, can cause of abnormal menstrual bleeding.
 the common skin wart is caused by an increased

expression of various transcription factors by an

infecting papillomavirus

 Hyperplasia and cancer
 It is important to note that, the hyperplastic process remains
controlled; if hormonal or growth factor stimulation abates,
the hyperplasia disappears.
 This differentiates these processes from cancer, in which
cells continue to grow despite the absence of hormonal
stimuli.
 Patients with endometrial hyperplasia increased risk of
developing endometrial cancer, and certain papillomavirus
infections predispose to cervical cancers
Pathologic hyperplasia of endometrium
 4. METAPLASIA
• Metaplasia Is Conversion of One Differentiated Cell
Type to Another.

•In molecular terms, metaplasia involves replacing the

expression of one set of differentiation genes with another.

•Metaplasia is usually an adaptive response to chronic,

persistent injury.

•Metaplasia is usually fully reversible. If the stimulus is

removed (e.g., when one stops smoking), the metaplastic
epithelium eventually returns to normal.
 Metaplasia
• Most commonly, glandular epithelium is replaced by
squamous epithelium. Columnar or cuboidal lining cells
resistant to the effects of chronic irritation or a chemical.
• For example, prolonged exposure of the bronchial
epithelium to tobacco smoke leads to squamous
metaplasia.
• A similar response occurs in the endocervix, associated
with chronic infection.
 Metaplasia
 Perubahan sel yang reversible. Satu jenis sel

dewasa berubah menjadi jenis sel lain

 Merupakan proses adaptasi sel terhadap stress

tertentu dari lingkungannya
 Contoh: metaplasia sel epitel torak pada saluran

napas menjadi sel epitel gepeng, akibat iritasi

kronik.
 Memberi efek samping dan dapat menimbulkan

tumor.
 Sebab yang lain: obat, zat kimia, bakteri dan

hormonal
It shows the normal columnar epithelium with
squamous metaplasia.
INTRACELLULAR ACCUMULATION
 cells may accumulate abnormal amounts of
various substances. These may be harmless or
may cause varied degrees of injury.
 The location of the substance may be either in the
cytoplasm, within organelles (typically
lysosomes), or in the nucleus.
 The substance may be synthesized by the affected
cells or may be produced elsewhere.
3 general pathways in abnormal
intracellular accumulations
 1. A normal or an abnormal endogenous
substance accumulates because of genetic or
acquired defects in its metabolism, packaging,
transport, or secretion. One example is a genetic
enzymatic defect in a specific metabolic
pathway; glycogen storage diseases.

 2. An abnormal exogenous substance is deposited and
accumulates because the cell has neither the enzymatic
machinery to degrade the substance nor the ability to
transport it to other sites.
 Accumulations of carbon or silica particles.

 3. A normal substance is produced at a normal or an

increased rate, but the metabolic rate is inadequate to
remove it. fatty change in the liver (see
 Mechanisms of intracellular accumul
 (1) abnormal metabolism, as in liver fatty change.
 (2) mutations causing alterations in protein folding and
transport, so that defective molecules accumulate
intracellularly;
 (3) a deficiency of critical enzymes responsible for breaking
down certain compounds, causing substrates to accumulate in
lysosomes, as in lysosomal storage diseases; and
 (4) an inability to degrade phagocytosed particles, as in
carbon pigment accumulation.
ATEROSKLEROSIS
Fatty change in the liver
Uric acid accumulation in gout
arthritis
Protein reabsorption droplets in the renal tubular
epithelium; the droplets are contained within
pinocytic vacuoles and within lysosomes
Hemosiderin granules in liver cells. A,
H & E-stained section showing golden-
brown, finely granular pigment.
 Hemosiderin in liver B, Prussian blue
reaction, specific for oxidized Fe+++ iron.
Accumulation of melanin, brown pigmen in
the skin
 CALCIFICATION
 Calcification Is a Normal or Abnormal Process
 The deposition of mineral salts of calcium is a
normal process in the formation of bone from
cartilage.
 Pathologic calcification is an abnormal
deposition of calcium salts, together with
smaller amounts of iron, magnesium, and other
minerals.
 Pathologic Calcification
 dystrophic calcification;
 the deposition of calcium in dead or dying tissues, it is

occurs in the absence of calcium metabolic derangements

(i.e., with normal serum levels of calcium).
Metastatic calcification;
 the deposition of calcium salts in normal tissues

 almost always reflects some derangement in calcium

metabolism (hypercalcemia).
An aortic valve . Nodules of calcification are seen on
the cusps here.
Thank you