Cellular Adaptation

Cell change (adapt in order to survive) their metabolism (alter equilibrium, new state) or growth
pattern in response to pathological or physiological stimuli. We see changes in biochemical markers,
structural changes, increase/decrease of cell numbers leading to hypertrophy or hypotrophy of
organs, cells changing from one type/form to another.

e.g. of metabolism being modified

 physiological
o during periods of relative lack of calcium, calcium is mobilized from the bone matrix
by osteoclast activity; Parathyroid hormone (PTH) when secreted by the parathyroid
gland stimulates bone to release calcium (bone resorption) to restore calcium levels
in blood
 pathological
o a tumour in the parathyroid gland, which is a disease process, leads to physiological
changes caused by an increased levels of PTH which results in bone resorption and
as a result excess Ca blood level

e.g. growth pattern change

 physiological
o during pregnancy, the uterus increases in size; this is because the smooth muscle
cells of the wall of the uterus and all the stromal components, things like fibroblasts
increase in number and size in response to increased levels of estrogen and
progesteron
 pathological
o an enlarged prostate gland in men, also called prostate gland hyperplasia is due to a
hormonal imbalance between the levels of androgen and estrogen; the cells in the
prostate gland become more receptive to estrogen than androgen which stimulated
the proliferation of prostate smooth muscle but also an increase of these cells’
volume

Normal growth
Cells develop from stem cells (primitive cells), undergo a series of mitotic divisions until they reach a
point where they start differentiating and acquire certain characteristics.

At maturity cells can be classified in 3 categories according to their growth pattern or capacity to
regenerate

 Labile cells
o Are cells that are constantly dividing to replace the ones that are lost; have a high
capacity to regenerate in other words have a high turnover or mitotic rate and short
life span, constantly being lost, constantly being replenished e.g. skin, mucous
membranes, bone marrow- RBC, WBC, lymph nodes
 Stable cells
o These cells divide occasionally under certain stimuli, when there is functional
demand to do so; they have a lower mitotic rate and longer life span e.g. liver,
kidney, glands increase in number under certain stimuli, whereas smooth muscle
cells increase in number and size
  Permanent cells
o Have either lost their capacity to divide (no mitotic activity) or have a very limited
capacity to do so; these cells are maintained for life unless they go through the
process of apoptosis or necrosis e.g. cardiac and skeletal muscle, neurons; while
neurons can’t increase in size the cardiac and skeletal muscle cells, under certain
physiological stimuli can adapt by increasing in size but not by number; During life
the cells with no capacity to divide are either lost progressively or get larger and
larger in size, but as you get older they get smaller.

Variations in growth
Cells demonstrate certain structural changes to pathological and physiological stimuli (adapt to
changing environment in order to survive) depending on their growth pattern or capacity to
regenerate:

o Increased cellular activity – cells increase in size or number

o Decreased cellular activity – reduction in size and number of cells e.g. atrophy of skeletal
muscle, cells decrease in size with some cells dying off
o Alterations of cell morphology - change in cell differentiation e.g. if the stimulus was
cigarette smoke the cells in the lung change from one cell type to another to basically
survive the offending chemical agents in tobacco; the columnar cells with cilia change to
stratified squamous cells which are more protective, but the problem is that these cells are
not specialized to that environment as the ciliated cells were, which can move the mucous
along

There are 11 variations of growth:

1) Hyperplasia – increase in mass of an organ due to an increase in the number of its

specialized constituent cells

e.g. physiological hyperplasia (physiological stimulus/physiological response)– during

puberty female breasts increase in size due to hormonal stimuli; lactating breasts increase in
size also due to hormonal stimulation during pregnancy; a gland comprises of glandular
tissue, fibrous tissue and fat tissue; the glandular cells are the once that increase in number
in anticipation of breast feeding

Another example is the thickening of the endometrium in response to oestrogen during the
menstrual cycle. This is due to proliferation of glandular cells forming the endometrium wall.

e.g. pathological hyperplasia (pathological stimulus/pathological response) – in

fibroadenosis of the breast, increases in the hormonal profile of estrogen leads to an
increase in the number of fibroblasts and glandular cells which increases the size of breast
tissue causing a pathological response/disease state of tissue

Another example is the skin callus forming due to chronic friction and the enlarged prostate
due to cells becoming more responsive to oestrogen than testosterone and fibroblasts and
glandular cells increase in number.

Another example is kidney atrophy. An enlarged prostate obstructs the urethra and urine
retention occurs in the bladder, ureter and renal pelvis which puts pressure on renal tissue
which results in kidney atrophy. Due to pressure, there is a thickening of the bladder wall;
the smooth muscle cells increase in number (hyperplasia) and size (hypertrophy).
 Individuals with Grave’s disease have antibodies that bind to the cell surface of the follicles
of the thyroid, acting like thyroid stimulating hormones when binding their receptors,
causing a hypersecretion of thyroxin. Too much thyroxin will result in an enlarged thyroid (a
swelling known as goitre) which compress the trachea causing respiratory problems.
Microscopically we can see an increase in the number of follicles (thyroxin is stored in the
follicles).

e.g. compensatory hyperplasia (pathological stimulus/physiological response) – if one

kidney is diseased or removed the one remaining undergoes hyperplasia as kidney cells
increase in number in order to compensate for the loss of function and cope with all the
physiological demands

e.g. reactive hyperplasia (pathological stimulus/physiological response) – lymph nodes

increase in size in infections because more lymphocytes get produced and released into the
blood to fight the infection

Another example is splenomegaly in infections (e.g. malaria); in malaria the plasmodium spp
parasite destroys blood cells; the spleen job is to get rid of damaged blood cells and produce
new blood cells during the infection; spleen increases in size due to an increase in number of
cells.

Hyperplasia is reversible when the stimulus is removed.

2) Hypertrophy – is the increase in mass of an organ due to an increase in size of its specialized
constituent cells; the increase in size is due to an increase in cellular elements: more Golgi,
more ribosomes, membranes, nuclei, enzymes, etc.

e.g. physiological hypertrophy – in athlete’s skeletal muscle get larger due to increased
functional demand

e.g. pathological hypertrophy – in hypertension the heart muscles increase in size; the heart
has to work harder to pump the blood into the systemic circulation; usually seen as a
hypertrophy of the left ventricle that pushes the blood into the aorta against that higher
blood pressure in the aorta/increased resistance

Smooth muscle undergoes a combination of hyperplasia and hypertrophy. In a gravid uterus

a physiological hypertrophy and hyperplasia of the myometrium (wall of uterus) can be seen
(an increase in number and size of smooth muscle cells and increase in number of the other
supporting cells such as fibroblasts)

3) Atrophy - is the opposite of both hyperplasia and hypertrophy, is the decrease in mass of an
organ due to a decrease in the size and number of its specialized constituent cells with a
return to normal size once the stimulus is removed (unless the cells have undergone
apoptosis).
The mechanism of decreasing in cell size is via autophagy – lysosomes release enzymes
resulting in auto-digestion of cellular components and of cytoplasmic structural proteins.
The mechanism of decreasing in cell numbers is via apoptosis.

e.g. physiological atrophy (involution) – the uterus after childbirth or menopause; testes
decrease in size in old age; involution of thymus gland after childhood, in adolescence it gets
smaller and the cells are replaced with adipose tissue
 e.g. pathological atrophy – skeletal muscles in poliomyelitis, pathogens attack the interior
horn cell in the spinal cord, nerves stop working causing a pathological atrophy of the
muscles; skeletal muscles atrophy due to immobilisation; hydronephrosis – retention of
urine in the renal pelvis which causes pressure and renal atrophy; brain atrophy in old age
due to dementia – thinner gyri and wider sulci; generalised pathological atrophy as seen in
malnutrition - Kwasiorkor or anorexia

4) Agenesis (absent at birth) – failure of an organ to develop at all due to errors during
embryonic embryogenesis; anencephaly – failure to develop a cerebrum (incompatible with
life); agenesis of kidney, one kidney or both (incompatible with life); amelia (no limbs)

5) Aplasia – sudden cessation of growth leading to decreased mass of tissue and defective
development of the organ caused by chemotherapy, radiotherapy, nuclear accidents of
bombs e.g. thymus gland aplasia during childhood – after the gland is developed if there is a
pathological stimulus like the ones mentioned above there is a sudden cessation of
maturation of T- cells leading to immunodeficiency; bone marrow aplasia – whereby the
bone marrow stop producing RBC causing aplastic anaemia

6) Hypoplasia – tissue fails to attain full size during foetal development leading to decreased
mass of tissue and incomplete development of organ; the organ is smaller than normal, not
absent, something goes wrong during development and the organ ends up smaller than
normal (deficient growth); e.g. cryptorchidism – baby boys have maldescended testes;
causes sterility; normally the testes develop in the abdomen and then descend in the
scrotum, shortly after birth, via the inguinal canal, where the temperature is lower 36.5 as
opposed to the abdomen where the temperature is 37 at which the sperm cannot function;
microcephaly – hypoplasia of brain causing neurological deficit

All three: agenesis, aplasia and hypoplasia are pathological responses to pathological stimuli
causing decreases in tissue mass.

All until now were about a change in cellular activity (growth), the following will be about a
change in cell differentiation.

7) Metaplasia – a fully differentiate adult cell changes into another more resilient but less
specialized fully differentiated adult cell type in response to chronic injury

e.g. Smokers’ airways – cigarettes; in smokers, due to pathological stimulus the columnar
ciliated cells change to stronger, more protective but less specialized type like stratified
squamous epithelium

e.g. Gallbladder – gall stones; normal columnar changes to stratified squamous epithelium

8) Dysplasia (premalignant condition) – if the pathological injury continues eventually the

epithelium becomes dysplastic which is a more sinister scenario; it represents an abnormal
growth and differentiation with loss of regularity of cells, loss of normal orientation and
relationship to one another (abnormal tissue organization) which leads to disordered,
atypical morphology, defective growth with a compromised function – the cells look
abnormal and very immature
 e.g. Oral cavity dysplasia – continuous irritation of tissue due to ill denture or smoking can
cause dysplasia of lip mucosa; respiratory tract dysplasia due to cigarettes smoking or
infective agents; cervix of uterus dysplasia due to HPV

9) Hamartoma – like tumours but are not tumours (they don’t have a capsule and do not show
uncontrollable growth); it is a focal overgrowth of normal cells found in a tissue in which
these cells are usually present e.g. benign naevus also called a “mole” showing melanocytes
proliferation; haemangioma also called “strawberry birthmark”– a proliferation of blood
vessels

10) Choristoma (Ectopia) – also showing a focal overgrowth of normal cells, but the cells are not
usually present in the tissue where they overgrown

e.g. endometriosis – endometrial cells usually grow in the lining of the uterus (endometrium)
but if it grows in the ovaries, or the wall of the uterus, or the fallopian tubes, or the wall of
the bowel then causes choristoma; and since this is normal tissue it responds to
physiological stimuli such as hormones regardless of where they grow, and at the time of the
monthly cycle will bleed from these other regions

e.g. when the endometrial cells grown in the myometrium (the wall of the uterus) they
cause adenomyosis (endometriosis in the wall of the uterus)

11) Neoplasia - is an abnormal, uncontrolled new growth of tissue, which has no coordinated
useful function in the body; even if the stimulus is removed the growth still continues; both
hyperplasia and neoplasia are new growths, but with hyperplasia tissue can go back to
normal if the stimulus is removed whereas with neoplasia it doesn’t.

There are 3 systems of classification of tumours:

1) Clinical classification
a. Describes the tumour as benign or malignant
b. How the tumour behaves – prognosis and its effects on the patient
2) Histogenetic
a. Indicates the origin of tumour, where it has risen
3) Morphologic
a. How the tumour looks with the naked eye

1) Clinical classification – identifies two main patterns of neoplastic growth

a. Benign – if the tumour grows only locally, is enclosed in a fibrous capsule and the
margins are well defined
i. Benign tumours grow slowly and are surrounded by CT capsule
ii. Well supported by abundant stroma; stroma – the tissue part of an organ
that has a connective and supporting role
iii. No infiltration/invasion of normal tissue – the tumour doesn’t grow in
between cells or destroy the normal cells
iv. Doesn’t spread to invade blood vessels or lymphatics
v. Easily treated, good prognosis
 b. Malignant – if the tumour is not contained in a fibrous capsule, grows into and
destroying surrounding tissue (invading blood vessels and lymphatic vessels causing
bleeding) and the margins are poorly defined
i. Malignant tumours grow rapidly and they don’t have the capsules
ii. They have scanty stroma which allows the cell to proliferate
iii. They have fragile vessels, so there is bleeding even in the actual tumour
iv. They infiltrate and invade the normal tissue, grow in between cells and
invade and destroy normal cells
v. They invade to distant parts (metastasis)
vi. Not easily treated, usually bad prognosis

Metastasis – it is the process whereby malignant tumours spread form their site of origin to
distant parts of the body forming secondary masses.

Primary tumours – a tumour that grows at the site of origin.

Secondary tumours – one that is growing distant from the site of origin, retaining the
histological characteristics of the tissue in which it arose; think of the analogy “seed-soil”
when thinking about metastasis; there are organs in the body which are fertile soil for
malignant cells to grow e.g. bone, lung, liver it really depends on the tissue structure and
biochemistry; if the tissue has a lot of space the tumour will seed there and grow
undisturbed; the liver has a great biochemistry and architecture for cancers to metastasize;
given the constant flow of blood through the kidney, the kidneys are not good for
metastasis.

Tumours can be staged – they are given a score to indicate the size of the primary tumour,
the degree to which they invaded locally, whether they have spread which provides
information about prognosis and clinical behaviour – how aggressive the tumour might be.
There are different staging systems, an example being the TNM where a T, N and M score is
given, T for the size of primary tumour, N for the lymph node involvement and M for the
extent of metastasis.
 Differentiation of tumours

A prognosis and clinical behaviour can be given to patients if the degree of differentiation is
known – how well the tumour is differentiated, the more poorly differentiated the more
aggressive the cancer and poorer prognosis.

o Well differentiated – the cell type is well recognized e.g. the breast cell the tumour
resembles the normal cells
o Poorly differentiated – the cells are barely recognizable as typical of tissue of origin
o Non-differentiated – the cells are not recognizable, we can’t say what is the tissue of
origin; special stains/immunofluorescent are used to determine origin
o Anaplastic – unknown tissue of origin

Poorly differentiated tumours showing features of malignancy:

o Pleomorphism – the cell size and shape is very varied in a tumour population
o High mitotic activity - the tumour population is rapidly dividing, proliferating
uncontrollably
o Abnormal mitoses – chromosomes separate in tripolar or bipolar configuration
o Hyperchromasia – cells separate and stain in a very dark colour
o Increased nucleus to cytoplasm ratio – the nucleus is disproportionally larger than the
size of cytoplasm

2) Histogenetic classification – indicates where the tumour has risen; refers to nomenclature
of tumours whereby the name of a tumour provides information about its cell of origin and
whether is benign or malignant.

Generally, benign tumours are given the suffix -oma whatever their tissue of origin is e.g.
osteoma, adenoma, epithelioma, fibroma

The prefix identifies the tissue osteo (bone) -oma (benign), adeno (gland) , fibro (fibroblast).

With malignant tumours, there are two rules: malignant tumours of epithelial origin are
given the suffix -carcinoma e.g. adenocarcinoma, hepatocarcinoma; malignant tumours of
mesenchymal (embryonic connective tissue) origin are given the suffix -sarcoma e.g.
osteosarcoma, fibrosarcoma.

There are also exceptions for those malignancies that have unknown tissue of origin.
3) Morphological classification – descriptive terminology to describe what the tumour looks
like with the naked eye or some other physical property is described such as palpatory
findings e.g. polyps in the colon or uterus; papillary (fungating) tumour – cauliflower like, in
adenocarcinoma; ulcerating tumours in colon or stomach; infiltrating – spreading
horizontally initially, rapidly spreading in tissue in melanoma; nodular – lump like in uterus
or breast; cystic – tumours filled with fluid in ovarian cysts.

Scirrhous = the tumour feels hard on palpation due to more collagen in the tumour
Encephaloid = the tumour feels soft on palpation due to more glandular tissue and less
collagen

Much information is gained about a tumour from the three classification systems