Introduction to Pathology

Dr Uzma Rihan
Pathology Department
 Introduction to Pathology
 Pathology is the study (logos) of disease (pathos).

 “Pathology" comes from the Greek words "pathos" meaning

"disease" and "logos" meaning “ study”

• Pathology is the study of the structural, biochemical, and

functional changes in cells, tissues, and organs that underlie
disease.

• Bridge between the basic sciences and clinical medicine

• Scientific foundation for all of medicine.

 Introduction to Pathology

 Traditionally the study of pathology is divided into:

• General pathology is concerned with the common reactions of

cells and tissues to injurious stimuli.

• Systemic pathology : morphological alterations & underlying

mechanisms occur organ/ tissue due to specific diseases e.g.;
ischemic heart disease, Pneumonia,
 Introduction to Pathology
 Four aspects of a disease process that form the core
of pathology are:

 Etiology or causes : Genetic or Acquired

 Pathogenesis : It is the sequence of cellular, biochemical & molecular

events that occur in cells or tissue after exposure to an injurious agent.

 Morphologic changes : Abnormal Anatomy

Gross, Microscopic, Radiological & Molecular

 Clinical manifestations: the functional abnormalities which lead to

signs & symptoms of a disease as well as clinical course and outcome.
Cellular Responses to Stress and Harmful
Stimuli
 Relationship between normal, adapted,
reversibly injured, and dead myocardial cells
 Cellular Responses to Stress and Noxious/
Harmful Stimuli

• Adaptations : reversible functional and structural responses to

changes in physiologic states and some pathologic stimuli.

• During adaptative process new but altered steady states are

achieved, allowing the cell to survive and continue to function.
 Cellular Responses to Stress and
Noxious/ Harmful Stimuli

 Four types of Adaptations occur in living bodies:

 Hypertrophy
 Hyperplasia
 Atrophy
 Metaplasia.

• When the stress is eliminated the cell can recover to its original
state without having suffered any harmful consequences
Cellular Responses to Stress and Noxious Stimuli

ALTERED PHYSIOLOGICAL CELLULAR ADAPTATIONS

STIMULI; SOME NONLETHAL
INJURIOUS STIMULI
 Increased work load,  Hyperplasia, hypertrophy   
increased stimulation (e.g., by
growth factors, hormones) .
  
 Decreased nutrients,
decreased stimulation,      Atrophy  
decreased work load
 
 Chronic irritation (physical or       Metaplasia
chemical)
 Cellular Responses to Stress and
Noxious Stimuli
• Cell injury occurs when:
 limits of adaptive responses are exceeded
 if cells are exposed to severe stress
 deprived of essential nutrients
 Genetic mutations that affect essential cellular constituents.

 Reversible cell injury

 Irreversible injury-----------------> Cell death.

 Two principal pathways of cell death in living tissue:

 Necrosis and
 Apoptosis.
 Adaptation, reversible injury, and cell death may be stages
of progressive impairment following different types of
insults
 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.
 HYPERTROPHY

• Hypertrophy : increase in
the size of cells, resulting in
an increase in the size of the
affected organ.

 Hypertrophied organ has no

new cells, just larger cells.
 HYPERTROPHY

 Synthesis of more intracellular structural components ---> increased size

of the cells.

 Dividing Cells may respond to stress -------> hyperplasia &

hypertrophy.

 Non dividing cells may respond to stress ----> hypertrophy.

• In many organs hypertrophy and hyperplasia may coexist and

contribute to increased size e.g. Breast & uterus
 HYPERTROPHY

• Types of Hypertrophy:
 Physiologic &
 Pathologic.

• Causes of hypertrophy:
 Increased functional demand (work load) e.g. hypertrophy of
heart in hypertension, aortic stenosis.

 Stimulation by hormones and growth factors e.g. hypertrophy of

breast & uterus in pregnancy.
 HYPERTROPHY

 The most common stimulus for

hypertrophy of striated muscle
is increased workload.
 Physiological hypertrophy

 For example, the bulging muscles of

bodybuilders result from an increase
in size of the individual muscle fibers
in response to increased demand.
Hypertrophy of left ventricular due to systemic hypertension, or aortic stenosis.
 HYPERTROPHY

• Increased workload causes:

 Synthesize of more proteins in
striated muscle cells.
 Increase in number of myofilaments
 Increase in the size of myocyte
 Increase the force generated by
myocytes --- increases the
strength and work capacity of
the muscle as a whole.
 HYPERTROPHY

 Hormone-induced Hypertrophy:
 The massive physiologic growth of the
uterus during pregnancy .

 Estrogen act on smooth muscle estrogen

receptors -------> increased synthesis of
smooth muscle proteins and an increase
in cell size

 Physiologic growth of the breast

during pregnancy
Hypertrophy is the result of increased production of cellular proteins.
 HYPERTROPHY

• Mechanisms of Hypertrophy :
• Hypertrophy is the result of increased production of
cellular proteins.

• Three basic steps in the molecular pathogenesis of cardiac

hypertrophy :
 Activation of surface receptors:
 Activation of mechanical sensors present on the cell surface
 Growth factors ( TGF-β, IGF-1, fibroblast growth factor) act on GFRs.
 Vasoactive agents (endothelin-1, and angiotensin II) act on their
receptors.
 HYPERTROPHY

 Signals originating from the surface receptors ------> activation of

transduction pathways.
• Two pathways:
• Phosphoinositide 3-kinase/AKT pathway.
• Signaling downstream of G protein-coupled receptors (induced by
many growth factors and vasoactive agents).

 These signaling pathways activates transcription factors such as:

 GATA4
 Nuclear factor of activated T cells(NFAT) &
 Myocyte enhancer factor 2 (MEF2).
 These transcription factors ----> increase synthesis of muscle
proteins -----> hypertrophy.
 HYPERTROPHY

 Hypertrophy is also associated with a switch of contractile

proteins from adult to fetal or neonatal forms.
 During muscle hypertrophy the α isoform of myosin heavy chain is
replaced by the β isoform, which has a slower, more energetic
economical contraction.

 Re expression of embryonic genes----> gene for Atrial natriuretic

factor (ANF) is expressed in both the atrium and the ventricle in the
embryonic heart, but it is down-regulated after birth.
 Cardiac hypertrophy, however, is associated with reinduction of ANF
gene expression.
 ANF is a diuretic therefore serves to reduce hemodynamic load.
 HYPERTROPHY

• Whatever the exact cause and mechanism of cardiac hypertrophy, it

eventually reaches a limit beyond which enlargement of muscle
mass is no longer able to compensate for the increased burden.

• At this stage several regressive changes occur in the myocardial

fibers--------> lysis and loss of myofibrillar contractile elements.
• In extreme cases myocyte death can occur by:
• Apoptosis or necrosis.

• The net result of these changes is cardiac failure.

• An adaptation to stress can progress to functionally
significant cell injury if the stress is not relieved.
Thanks