BRANCHES OF HUMAN PATHOLOGY AND

CELLULAR RESPONSES TO STRESS AND

NOXIOUS STIMULI

ANTHONY M.
R.N, BScN (UoN)
• Human pathology is studied under two broad divisions:
• GENERAL PATHOLOGY: deals with general principles
of disease
• SYSTEMIC PATHOLOGY: that includes study of
disease pertaining to the specific organ and body
systems.
 MORPHOLOGICAL BRANCHES
• Mainly involve application of microscope as an essential tool for the study and
include histopathology, cytopathology and haematology.
• Histopathology: The study includes structural changes by naked eye
examination referred as gross or macroscopic changes, and the changes detected
by microscopy, which may be further supported by numerous special staining
methods such as histochemistry and immunohistochemistry to arrive at the
most accurate diagnosis.
• Surgical pathology: it deals with study of tissue removed from the living body
by biopsy or surgical resection.
• Surgical pathology forms the bulk of tissue material for the pathologist and
includes study of tissue by conventional paraffin embedding technique,
incorporative frozen section may be employed for rapid diagnosis.
• Experimental pathology: this is defined as production of disease in the
experimental animal and study of morphological changes in organs after
sacrificing the animal. However, all the findings of experimental work in animals
may not be applicable to human beings due to specific difference.
• Forensic pathology and autopsy: it includes the study of organs and tissues
removed at postmortem for medicolegal work and for determining the underlying
sequence and cause of death.
• Postmortem anatomical diagnosis is helpful to the clinician to enhance his
knowledge about the disease and his judgment while forensic autopsy is helpful
for medicolegal purpose.
• The significance of a careful postmortem examination is appropriately summed up
in the old saying the dead teach the living.
• Cytopathology: though a branch of anatomic pathology,
cytopathology has developed as a distinct subspeciality in
recent times. It includes study of cells shed off from the
lesions (eg foliative cytology) and fine needle aspiration
cytology (FNAC) of superficial and deep seated lesions for
diagnosis.
• Haematology: deals with disease of blood.
• It includes laboratory haematology and clinical haematology;
the latter covers the management of patient as well.
 NON MORPHOLOGICAL BRANCHES

.Clinical Pathology: analysis of various body fluids such as

blood, urine, semen, CSF and other fluids.
• Clinical biochemistry: quantitative determination of various
biochemical constituents in serum and plasma and in the
other body fluids.
• Microbiology: it includes study of disease causing
microbes implicated to human disease.
• Depending upon the type of micro organisms studied it has
further developed into bacteriology, parasitology, mycology,
virology etc.
• Immunology: detection of abnormalities in the immune system
of the body comprises immunology and immunopathology.
• Medical genetics: this is branch of human genetics that deals
with relationships between hereditary and disease.
• Molecular pathology: the detection and diagnosis of
abnormalities at the level of DNA of the cell is included in
molecular pathology for eg in situ hybridization, PCR etc. these
methods are now apart from research are used in diagnostic
pathology reports.
 TERMS USED IN PATHOLOGY:

• PATIENT is the person affected by disease.

• LESIONS are the characteristics changes in tissue and cells produced by
disease in an individual or experimental animal.
• PATHOLOGICAL CHANGES/MORPHOLOGY consists of examination of
diseased tissues. These can be recognized with the naked eye or studied by
microscopic examination of tissue.
• PATHOGENESIS OF DISEASE Mechanism by which lesions are produced.
• Functional implications of the lesion felt by the patient are symptoms and those
discovered by the clinician are the physical sign.
• DIAGNOSIS is clinical significance of the morphological and functional changes
together with results of other investigations help to arrive at an answer about
what is the exact problem.
• PROGNOSIS is what will happen next after the disease has occurred.
• TREATMENT ; What can be done about that problem.
• PREVENTION; what should be done to avoid complications and its spread.
 CELLULAR RESPONSES TO STRESS AND
NOXIOUS STIMULI
• The normal cell is confined to a fairly narrow range of function and
structure by its state of metabolism, differentiation, and
specialization; by constraints of neighboring cells; and by the
availability of metabolic substrates.
• It is nevertheless able to handle physiologic demands, maintaining
a steady state called homeostasis.
• Adaptations are reversible functional and structural responses to
more severe physiologic stresses and some pathologic stimuli,
during which new but altered steady states are achieved, allowing
the cell to survive and continue to function
• The adaptive response may consist of an increase in the size of cells
(hypertrophy) and functional activity, an increase in their number
(hyperplasia), a decrease in the size and metabolic activity of cells
(atrophy), or a change in the phenotype of cells (metaplasia).
• When the stress is eliminated the cell can recover to its original state without
having suffered any harmful consequences.
• If the limits of adaptive responses are exceeded or if cells are exposed to
injurious agents or stress, deprived of essential nutrients, or become
compromised by mutations that affect essential cellular constituents, a
sequence of events follows that is termed cell injury
• Cell injury is reversible up to a certain point, but if the stimulus persists or is
severe enough from the beginning, the cell suffers irreversible injury and
ultimately cell death.
• Adaptation, reversible injury, and cell death are the stages of progressive
impairment following different types of insults.
• For instance, in response to increased hemodynamic loads, the heart muscle
becomes enlarged, a form of adaptation, and can even undergo injury. If the
blood supply to the myocardium is compromised or inadequate, the muscle first
suffers reversible injury, manifested by certain cytoplasmic changes. Eventually,
the cells suffer irreversible injury and die
• Cell death, the end result of progressive cell injury, is one of the most crucial events in the evolution
of disease in any tissue or organ.
• It results from diverse causes, including ischemia (reduced blood flow), infection, and toxins.
• Cell death is also a normal and essential process in embryogenesis, the development of organs, and
the maintenance of homeostasis.
• There are two principal pathways of cell death, necrosis and apoptosis.
• Nutrient deprivation triggers an adaptive cellular response called autophagy that may also
culminate in cell death.
• Metabolic derangements in cells and sublethal, chronic injury may be associated with intracellular
accumulations of a number of substances, including proteins, lipids, and carbohydrates. Calcium is
often deposited at sites of cell death, resulting in pathologic calcification. Finally, the normal process
of aging itself is accompanied by characteristic morphologic and functional changes in cells.
 ADAPTATIONS OF CELLULAR GROWTH
AND DIFFERENTIATION

• Adaptations are reversible changes in the size,

number, phenotype, metabolic activity, or
functions of cells in response to changes in their
environment.
• Such adaptations may take several distinct
forms which includes;
 HYPERTROPHY
• Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of
the organ.
• The hypertrophied organ has no new cells, just larger cells.
• The increased size of the cells is due to the synthesis of more structural components of the
cells.
• Cells capable of division may respond to stress by undergoing both hyperplasia and
hypertrophy, whereas in non dividing cells (e.g., myocardial fibers) increased tissue mass
is due to hypertrophy.
• In many organs hypertrophy and hyperplasia may coexist and contribute to increased size.
• Hypertrophy can be physiologic or pathologic and is caused by increased functional
demand or by stimulation by hormones and growth factors.
• The striated muscle cells in the heart and skeletal muscles have only a limited capacity for
division, and respond to increased metabolic demands mainly by undergoing hypertrophy
• The most common stimulus for hypertrophy of muscle
is increased workload
• For example, the bulging muscles of bodybuilders.
• In the heart, the stimulus for hypertrophy is usually
chronic hemodynamic overload, resulting from either
hypertension or faulty valves
• Physiologic hypertrophy of the uterus during
pregnancy.
• The massive physiologic growth of the uterus during pregnancy is a good
example of hormone-induced increase in the size of an organ that results mainly
from hypertrophy of muscle fibers.
• The cellular enlargement is stimulated by estrogenic hormones acting on
smooth muscle estrogen receptors, eventually resulting in increased synthesis
of smooth muscle proteins and an increase in cell size
• Mechanisms of hyperthrophy •
• the result of increased production of cellular proteins •
• can be induced by the linked actions of mechanical sensors, growth factors etc
• Hypertrophy can also be drug induced for instance, individuals treated with
drugs such as barbiturates show hypertrophy of the smooth endoplamic
reticulum (ER) in hepatocytes
 HYPERPLASIA

• Hyperplasia is an increase in the number of cells in an organ or tissue, usually

resulting in increased mass of the organ or tissue
• Hyperplasia takes place if the cell population is capable of dividing, and thus
increasing the number of cells.
• Hyperplasia can be physiologic or pathologic occuring together with hypertrophy
• Physiologic Hyperplasia
• 1. hormonal hyperplasia, which increases the functional capacity of a tissue when
needed Hormonal hyperplasia is well illustrated by the proliferation of the glandular
epithelium of the female breast at puberty and during pregnancy, usually
accompanied by enlargement (hypertrophy) of the glandular epithelial cells.
• compensatory hyperplasia, which increases tissue mass after
damage or partial resection.
• In individuals who donate one lobe of the liver for
transplantation, the remaining cells proliferate so that the organ
soon grows back to its original size
• Pathologic Hyperplasia • Most forms of pathologic hyperplasia
are caused by excesses of hormones or growth factors acting on
target cells.
• Endometrial hyperplasia is an example of abnormal hormone-
induced hyperplasia
• It is brought to a halt by the rising levels of progesterone, usually about 10 to 14
days before the end of the menstrual period.
• In some instances, however, the balance between estrogen and progesterone is
disturbed. This results in absolute or relative increases in the amount of estrogen,
with consequent hyperplasia of the endometrial glands.
• This form of pathologic hyperplasia is a common cause of abnormal menstrual
bleeding.
• Severe gingival hyperplasia caused by Cyclosporin in a renal transplant patient.
• Hyperplasia is a characteristic response to certain viral infections, such as
papillomaviruses, which cause skin warts and several mucosal lesions composed
of masses of hyperplastic epithelium. Here, growth factors produced by viral
genes or by infected cells may stimulate cellular proliferation
 ATROPHY
• Atrophy is reduced size of an organ or tissue resulting from a decrease in cell size and
number.
• Atrophy can be physiologic or pathologic.
• Physiologic atrophy is common during normal development.
• Some embryonic structures, such as the notochord and thyroglossal duct, undergo
atrophy during fetal development.
• The uterus decreases in size shortly after parturition, and this is a form of physiologic
atrophy
• The common causes of atrophy are the following
• 1. Decreased workload (atrophy of disuse). When a fractured bone is immobilized in
a plaster cast or when a patient is restricted to complete bedrest, skeletal muscle
atrophy rapidly ensues. The initial decrease in cell size is reversible once activity is
• 2. Loss of innervation (denervation atrophy). The normal
metabolism and function of skeletal muscle are dependent on its
nerve supply. Damage to the nerves leads to atrophy of the muscle
fibers supplied by those nerves
• 3. Diminished blood supply. A decrease in blood supply (ischemia)
to a tissue as a result of slowly developing arterial occlusive disease
results in atrophy of the tissue. In late adult life, the brain may
undergo progressive atrophy, mainly because of reduced blood
supply as a result of atherosclerosis This is called senile atrophy; it
also affects the heart.
• 4. Inadequate nutrition. Profound protein- calorie malnutrition
(marasmus) is associated with the use of skeletal muscle as a source of
energy after other reserves such as adipose stores have been depleted
• 5. Loss of endocrine stimulation. Many hormone-responsive tissues,
such as the breast and reproductive organs, are dependent on endocrine
stimulation for normal metabolism and function. The loss of estrogen
stimulation after menopause results in physiologic atrophy of the
endometrium, vaginal epithelium, and breast.
• 6. Pressure. Tissue compression for any length of time can cause atrophy. An
enlarging benign tumor can cause atrophy in the surrounding uninvolved tissues.
Atrophy in this setting is probably the result of ischemic changes caused by
compromise of the blood supply by the pressure exerted by the expanding mass.
• Mechanisms of Atrophy
• Atrophy results from decreased protein synthesis and increased protein
degradation in cells. Protein synthesis decreases because of reduced metabolic
activity. • In many situations, atrophy is also accompanied by increased
autophagy, with resulting increases in the number of autophagic vacuoles.
Autophagy (“self eating”) is the process in which the starved cell eats its own
components in an attempt to find nutrients and survive.
 METAPLASIA
• Metaplasia is a reversible change in which one differentiated cell type (epithelial or
mesenchymal) is replaced by another cell type.
• It may represent an adaptive substitution of cells that are sensitive to stress by cell
types better able to withstand the adverse environment.
• The most common epithelial metaplasia is columnar to squamous, as occurs in the
respiratory tract in response to chronic irritation.
• In the habitual cigarette smoker, the normal ciliated columnar epithelial cells of the
trachea and bronchi are often replaced by stratified squamous epithelial cells.
• Stones in the excretory ducts of the salivary glands, pancreas, or bile ducts may
also cause replacement of the normal secretory columnar epithelium by stratified
squamous epithelium
• A deficiency of vitamin A (retinoic acid) induces squamous metaplasia in the
respiratory epithelium
• In all these instances the more rugged stratified squamous epithelium is able to survive
under circumstances in which the more fragile specialized columnar epithelium might have
succumbed.
• However, the change to metaplastic squamous cells comes with a price.
• In the respiratory tract, for example, although the epithelial lining becomes tough, important
mechanisms of protection against infection— mucus secretion and the ciliary action of the
columnar epithelium—are lost.
• Thus, epithelial metaplasia is a double-edged sword and, in most circumstances, represents
an undesirable change.
• Moreover, the influences that predispose to metaplasia, if persistent, may initiate malignant
transformation in metaplastic epithelium.
• Thus, a common form of cancer in the respiratory tract is composed of squamous cells, which
arise in areas of metaplasia of the normal columnar epithelium into squamous epithelium.