by Lami A 03/02/2025

INTRODUCTION TO PATHOPHYSIOLOGY

By: Lami A
(BScN, MSc)
1
 by Lami A 03/02/2025

Objectives
Learning Objectives
 Upon completing this topic students

should be able to:

1. Define pathology
2. Discuss the core aspects of disease in
pathology

2
 by Lami A 03/02/2025

The core aspects of diseases in pathology

 Pathology is the study of disease by scientific methods.
 The word pathology came from the
Latin words “patho” & “logy”. ‘Patho’ means disease and
‘logy’ means study.
 Diseases may, in turn, be defined as an abnormal
variation in structure or function of any part of the body.

3
 by Lami A 03/02/2025

Pathology gives explanations of a disease by studying

the following four aspects of the disease.
1. Etiology,
2. Pathogenesis,
3. Morphologic changes and
4. Functional derangements and clinical significance.

4
 by Lami A 03/02/2025

CELLULAR ADAPTATIONS,
CELL INJURY AND CELL
DEATH

5
 by Lami A 03/02/2025

- The normal cell is confined to a fairly normal range

of function & structure.
- It is nevertheless able to handle normal physiologic
demands, maintaining steady state called
homeostasis.
- More severe physiologic stresses & some pathologic
stimuli may bring about a number of physiologic &
morphologic cellular adaptation.

6
 by Lami A 03/02/2025

Cellular adaptation
- It is a new but altered steady state
which preserves the viability of the cell
& modulates its function as it responds
to a stimuli.

7
 by Lami A 03/02/2025

HYPERPLASIA
- It is an increase in number of cells in an organ or
tissue , usually resulting in increased volume of
the organ or tissue

8
 by Lami A 03/02/2025

A. PHYSIOLOGIC HYPERPLASIA
1. Hormonal hyperplasia which increases the
functional capacity of a tissue when needed.
eg. Proliferation of glandular epithelium of female
breast during pregnancy & puberty or physiologic
hyperplasia that occurs in pregnant uterus.
B. Pathologic hyperplasia
- Most are caused by excessive hormonal stimulation
or growth factors acting on target cells
- eg. Endometrial hyperplasia (due to estrogen),
benign prostatic hyperplasia (due to androgen)
9
 by Lami A 03/02/2025

HYPERTROPHY
- It refers to an increase in the size of cells ,
resulting in an increase in the size of the organ.

- The increase in size is due to synthesis of more

structural components

- It can be physiologic or pathologic & is caused by

increased functional demand or by specific
hormonal stimulation

- Example:
 the enlargement of the left ventricle in

hypertensive heart disease & the increase in

10
skeletal muscle during strenuous exercise
 by Lami A 03/02/2025

ATROPHY

- Shrinkage in the size of the cell by loss of cell

substance
- Atrophy can be physiologic or pathologic
- Physiologic atrophy is common during early
development .
- Early embryonic structures such as thyroglossal duct
undergo atrophy during fetal development.
- Uterus decreases in size shortly after parturition.
11
 by Lami A 03/02/2025

PATHOLOGIC ATROPHY…
 can be local or generalized

 The common causes of atrophy are the following

 Decreased work load (Atrophy of disuse)
 Loss of innervation (denervation atrophy)
 Diminished blood supply
 Inadequate nutrition
 Loss of endocrine stimulation
 Aging
 Pressure

12
 by Lami A 03/02/2025

METAPLASIA

- It is a reversible change in which one adult cell type

(epithelial or mesenchymal) is replaced by another
adult 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

13
 by Lami A 03/02/2025

METAPLASIA….

- The most common metaplasia is columnar to squamous.

The normal ciliated columnar epithelial cells of the
trachea & bronchi are often replaced focally or widely by
stratified squamous epithelial cells in cigarette smokers

- The influences that predispose to metaplasia , if

persistent, may induce malignant transformation in
metaplastic epithelium

14
 by Lami A 03/02/2025

CELL INJURY
 Cell injury results when cells are stressed so

severely that they no longer able to adapt or the

cells are exposed to inherently damaging agents .

 These alterations may be divided into the

following stages

 Reversible cell injury – is manifested as

functional & morphologic changes that are

reversible if the damaging stimulus is removed

 Irreversible injury or cell death – with 15

 by Lami A 03/02/2025
CAUSES OF CELL INJURY

 Oxygen deprivation
- Hypoxia is a deficiency of oxygen , which causes cell injury by reducing
aerobic oxidative respiration.
It should be distinguished from ischemia , which is loss of blood supply from
impeded arterial flow or reduced venous drainage in tissue
- Causes of hypoxia include cardiorespiratory failure, anemia, carbon
monoxide poisoning

 Physical agents – mechanical trauma, extremes of temperature, sudden

changes in atmospheric pressure

 Chemical agents & Drugs

 Infectious agents

 Immunologic reactions

 Genetic derangements

 Nutritional imbalance 16
 by Lami A 03/02/2025

MECHANISMS OF CELL INJURY

- Principles that are relevant to most forms of cell injury

 The cellular response to injurious stimuli depends on

the type of injury, its duration & its severity

 The consequences of cell injury depend on the type,

state, & adaptability of the injured cell

17
 by Lami A 03/02/2025

MORPHOLOGY OF CELL INJURY & NECROSIS

Reversible injury
Two patterns of reversible cell injury can be recognized under
the light microscope
Cell swelling
- The first manifestation of injury
- It appears whenever the cells are incapable of maintaining
ionic & fluid homeostasis & is result of loss of function of
plasma membrane energy-dependent ion pumps.

18
 by Lami A 03/02/2025

Fatty change
- It is manifested by the appearance of small & large
lipid vacuoles in the cytoplasm & occurs in hypoxic &
various toxic injury.
- It is principally seen in cells involved in & dependent
on fat metabolism such as hepatocytes & myocardial
cell

19
 by Lami A 03/02/2025

Cell death
- Necrosis
- Apoptosis

20
 by Lami A 03/02/2025

NECROSIS

- It refers to a spectrum of morphologic changes that

follow cell death in a living tissue resulting from the
progressive degradative action of enzymes in
lethally injured cells.
- Necrosis is cell death occurring in the setting of
irreversible exogenous injury.
- Necrotic cells aren’t able to maintain membrane
integrity & their content leak out & elicit
inflammation in the surrounding tissue
21
 by Lami A 03/02/2025

…
- Necrotic cells show increased eosinophilia due to
loss the normal basophilia imparted by RNA in the
cytoplasm

Nuclear changes
- Karyolysis – The basophilia of the nucleus fades
- Pyknosis- Nuclear shrinkage & increased
basophilia
- Karyorrhexis – Nuclear fragmentation

22
 by Lami A 03/02/2025

Morphologic patterns of necrosis

Coagulative necrosis
- Most often results from sudden interruption of blood
supply to an organ.
- It is, in early stages, characterized by general
preservation of tissue architecture when
denaturation is the primary pattern

23
 by Lami A 03/02/2025

…
Liquefactive necrosis
- It is characterized by digestion of tissue.
It shows softening & liquefaction of tissue.
- characteristically results from ischemic injury to the
CNS.
-also occurs in supportive infections characterized by
formation of pus.
Gangrenous necrosis
- It is due to vascular occlusion & most affects the
lower extremities & the bowel.

24
 by Lami A 03/02/2025

…
Caseous necrosis
- It is type of necrosis most often seen in foci of
tuberculosis infection.
- The term caseous is derived from the cheesy white gross
appearance of the area of necrosis
- On microscopic examination, the necrotic focus appears
as amorphous granular debris enclosed within a
distinctive inflammatory border known as a
granulomatous reaction

25
 by Lami A 03/02/2025

Fat necrosis
- Focal areas of fat destruction, typically occurring as
a result of release of activated pancreatic lipases
into the substance of the pancreas & the peritoneal
cavity. This occurs in acute pancreatitis.
- The activated enzymes liquefy fat cell membranes
&The lipases split the triglyceride contained with in
fat cells.

26
 by Lami A 03/02/2025

Apoptosis
- It is a pathway of cell death that is induced by tightly
regulated intracellular program in which cells
destined to die activate enzymes that degrade the
cells’ own nuclear DNA & nuclear & cytoplasmic
proteins.

27
 by Lami A 03/02/2025

…
Apoptosis in physiologic situations
- Programmed destruction of cells during
embryogenesis
- Hormone –dependent involution in the adult such
as endometrial cell breakdown during menstrual
cycle .
- the regression of the lactating breast after
weaning.

28
 by Lami A 03/02/2025

Apoptosis in Pathologic conditions

- Cell death produced by a variety of injurious

stimuli such as radiation & cytotoxic anticancer

drugs

- Cell injury in certain viral diseases such as viral

hepatitis

- Pathologic atrophy in parenchymal organs after

duct obstruction.

- Cell death in tumors.

29
 by Lami A 03/02/2025

FEATURES OF NECROSIS AND APOPTOSIS

Feature Necrosis Apoptosis

Cell size Enlarged (swelling) Reduced (shrinkage)
Nucleus Pyknosis - Fragmentation into
karyorrhexis - nucleosome size
karyolysis fragments
Plasma membrane Disrupted Intact; altered
structure, especially
orientation of lipids
Cellular contents Enzymatic digestion; Intact; may be
may leak out of cell released in apoptotic
bodies
Adjacent Frequent No
inflammation
Physiologic or Invariably pathologic Often physiologic,
pathologic role (culmination of means of eliminating
irreversible cell unwanted cells; may
injury) be pathologic 30
 by Lami A 03/02/2025

ACUTE AND CHRONIC INFLAMMATION

31
 by Lami A 03/02/2025

INTRODUCTION:
 “Inflame” – to set fire.
 Inflammation is “dynamic response of
vascularised ,living tissue to injury.”
 Is a protective, physiologic response.
 It is intended to
 Contain and isolate injury,
 Destroy invading microorganisms and inactivate
toxins, and
 Prepare the tissue for healing and repair

32
 by Lami A 03/02/2025

 The ultimate goal

 to rid the organism of both the initial cause of cell
injury (e.g., microbes, toxins) and the
consequences of such injury (e.g., necrotic cells
and tissues).
 Without inflammation,
 infections would go unchecked,
 wounds would never heal, and
 injured organs might remain permanent festering
33
 by Lami A 03/02/2025

…
 The inflammatory response consists of two main
components,
 A vascular reaction and
 A cellular response
 Tissues and cells involved in these reactions, include
 the fluid and proteins of plasma,
 circulating cells,
 blood vessels, and
34
 by Lami A 03/02/2025

…
 Inflammation is divided into acute and chronic
patterns.
 Acute inflammation
 Rapid in onset (seconds or minutes)
 Relatively of short duration, lasting for
minutes, several hours, or a few days;
 Main characteristics are the exudation of fluid
and plasma proteins (edema) and the
emigration of leukocytes, predominantly
35
neutrophils.
 by Lami A 03/02/2025

 Chronic inflammation
 is of longer duration
 Associated histologically with the presence of
lymphocytes and macrophages, the
proliferation of blood vessels, fibrosis, and
tissue necrosis.

36
 by Lami A 03/02/2025

ACUTE INFLAMMATION
 It is a rapid response to an injurious agent that

serves to deliver mediators of host defense—

leukocytes and plasma proteins—to the site of

injury.

 has three major components:

1. Alterations in vascular caliber an increase in blood flow

2. Structural changes in the microvasculature plasma

proteins and leukocytes leave the circulation; and

3. Emigration of the leukocytes from the microcirculation,

37
 by Lami A 03/02/2025

NOTE

 An Exudate
 an inflammatory extravascular fluid
 has a high protein concentration, cellular debris, and
 a specific gravity above 1.020.
 It implies significant alteration in the normal
permeability of small blood vessels in the area of
injury.

38
 by Lami A 03/02/2025

…
 A transudate
 a fluid with low protein content (most of which is
albumin) and
 a specific gravity of less than 1.012.
 It is essentially an ultrafiltrate of blood plasma
that results from osmotic or hydrostatic imbalance
across the vessel wall without an increase in
vascular permeability.

39
 by Lami A 03/02/2025

 Edema
 an excess of fluid in the interstitial or serous
cavities; it can be either an exudate or a
transudate.

 Pus, a purulent exudate,

 An inflammatory exudate rich in leukocytes
(mostly neutrophils), the debris of dead cells and,
in many cases, microbes.
40
 by Lami A 03/02/2025

STIMULI FOR ACUTE INFLAMMATION

 Acute inflammatory reactions are triggered by a

variety of stimuli:

 Infections

 bacterial, viral, parasitic

 microbial toxins

 Trauma (blunt and penetrating)

 Physical and chemical agents (thermal injury, e.g.,

burns or frostbite; irradiation; some environmental

chemicals) 41
 by Lami A 03/02/2025

CHEMOTAXIS

 After extravasation, leukocytes emigrate in tissues

toward the site of injury by a process called
chemotaxis, defined most simply as locomotion
oriented along a chemical gradient.
 All granulocytes, monocytes and, to a lesser
extent, lymphocytes respond to chemotactic
stimuli with varying rates of speed.

42
 by Lami A 03/02/2025

CHEMICAL MEDIATORS OF INFLAMMATION

 Many mediators have been identified,

and how they function in a coordinated
manner is still not fully understood.
 some of the major mediators:

43
 by Lami A 03/02/2025

CARDINAL SIGNS OF
INFLAMMATION
 Rubor : Redness – Hyperaemia.
 Calor : Warm – Hyperaemia.
 Dolor : Pain – Nerve, Chemical med.
 Tumor: Swelling – Exudation
 Loss of Function:

44
by Lami A 03/02/2025

45
 by Lami A 03/02/2025

TISSUE RENEWAL AND REPAIR

46
 by Lami A 03/02/2025

INTRODUCTION

 The body's ability to replace injured or dead cells and to

repair tissues after inflammation is critical to survival.
 When injurious agents damage cells and tissues, the
host responds by setting in motion a series of events
that serve
 to eliminate these agents,
 contain the damage, and
 prepare the surviving cells for replication.

47
 by Lami A 03/02/2025

PROCESSES OF WOUND HEALING

1.Regeneration
2.Repair,scar formation,fibrosis

48
 by Lami A 03/02/2025

CONT…

Regeneration -proliferation of cells and

tissues to replace lost structures
E.g

 liver
growth after partial resection or
necrosis, but these processes consist of
compensatory growth rather than true
regeneration.

49
 by Lami A 03/02/2025

CONT…

Repair most often consists of a combination of

regeneration and scar formation by the
deposition of collagen
 relative contribution of regeneration and
scarring in tissue repair depends on the
ability of the tissue to regenerate and the
extent of the injury
50
 by Lami A 03/02/2025

REGENERATION

 Regeneration refers to growth of cells and tissues to

replace lost structures.
 In mammals, whole organs and complex tissues
rarely regenerate after healing, and the term is
usually applied to processes such as liver and kidney
growth after, respectively, partial hepatectomy and
unilateral nephrectomy.

51
 by Lami A 03/02/2025

REPAIR BY HEALING, SCAR FORMATION,

AND FIBROSIS

 By contrast, healing is a fibroproliferative response .

 If tissue injury is severe or chronic, and results in damage of

both parenchymal cells and the stromal framework of the

tissue, healing can not be accomplished by regeneration.

Under these conditions, the main healing process is repair

by deposition of collagen and other ECM components,

causing the formation of a scar.

52
 by Lami A 03/02/2025

REPAIR …
It is a complex but orderly phenomenon involving a

number of processes:

• Induction of an inflammatory process in

response to the initial injury

• Proliferation and migration of parenchymal and connective

tissue cells

• Formation of new blood vessels (angiogenesis) and

granulation tissue

• Synthesis of ECM proteins and collagen deposition

• Tissue remodeling 53
 by Lami A 03/02/2025

REPAIR BY CONNECTIVE TISSUE

 Occurs when repair by parenchymal regeneration

alone cannot be accomplished
 Involves production of Granulation Tissue-
Replacement of parenchymal cells with proliferating
fibroblasts and vascular endothelial cells.

54
 by Lami A 03/02/2025

PATTERN OF isWOUND
Such healing HEALING
referred to as primary union or
healing by first intention.
The incision causes death of a limited number of

epithelial and connective tissue cells as well as

disruption of epithelial basement membrane
continuity.
Sequence of events in primary wound healing
Day1.
Neutrophils appear at the margin of the incision,

move towards the

fibrin clot
Day 2. epithelial cells move from the wound edge
along the cut margins of dermis and deposit
basement membrane

55
 by Lami A 03/02/2025

Day3.
 neutrophils are replaced by macrophages
 Granulation tissue formation
 Collagen fiber formation begin
 Epithelial cell proliferation thickens the epidermal

layer
Day5 .
 the incisional space is filled with granulation tissue
 Maximal neovascularization
 More abundant collagen fibers which start to bridge

the incision
 The epidermis recovers its normal thickness

Week 2.
 continuous accumulation of collagen and proliferation

of fibroblasts 56
 by Lami A 03/02/2025

HEALING BY SECOND INTENTION (WOUNDS WITH SEPARATED EDGES)

 When there is more extensive loss of cells and tissue,

as in surface wounds that create large defects, the
reparative process is more complicated.
 Regeneration of parenchymal cells cannot
completely restore the original architecture, and
hence abundant granulation tissue grows in from the
margin to complete the repair.
 This form of healing is referred to as secondary
union or healing by second intention.

57
 SECOND INTENTION… by Lami A 03/02/2025

•Secondary healing differs from primary healing in several

respects:
the inflammatory reaction is more intense.
Much larger amounts of granulation tissue are
formed.
wound contraction, Perhaps the feature that
most clearly differentiates primary from
secondary healing.
Contraction of these cells at the wound site
decreases the gap between the dermal edges
of the wound.

58
 by Lami A 03/02/2025

FACTORS AFFECTING HEALING:

Systemic Local
 Nutrition  necrosis
 Vitamin def.(particularly vit
c)  Infection
 Age  apposition
 Immune status  Blood supply
 Metabolic status(e.g DM)
 Circulatory status(e.g in
 Mobility
arteriosclerosis, varicos  Foreign body
vein)
 Hormones(e.g
glucocorticoids)inhibit
collagen synthesis
 Other diseases

59
 by Lami A 03/02/2025
COMPLICATIONS IN CUTANEOUS WOUND
HEALING

 Complications in wound healing can arise from

abnormalities in any of the basic components of the
repair process.
 These aberrations can be grouped into three
general categories:
1) Deficient scar formation(wound dehiscence,
ulcers)
2) Excessive formation of the repair
components(hypertrophic scar, keloid, exuberant
60
 by Lami A 03/02/2025

 The accumulation of excessive amounts of collagen

may give rise to a raised scar known as a
hypertrophic scar; if the scar tissue grows beyond
the boundaries of the original wound and does not
regress, it is called a keloid.
• Keloid formation appears to be an individual
predisposition, and for unknown reasons this
aberration is somewhat more common in African-
Americans. 61
 by Lami A 03/02/2025

NOTE

 Contraction in the size of a wound is an important

part of the normal healing process.
 An exaggeration of this process is called a
contracture and results in deformities of the wound
and the surrounding tissues.
 Contractures are particularly prone to develop on the
palms, the soles, and the anterior aspect of the
thorax.
 Contractures are commonly seen after serious burns
62
by Lami A 03/02/2025

63
 by Lami A 03/02/2025

NORMAL HEMOSTASIS

 Normal hemostasis is a consequence of tightly regulated

processes that maintain blood in a fluid state in normal vessels,
yet also permit the rapid formation of a hemostatic clot at the site
of a vascular injury.
 deranged in two groups disorders
 Hemorrhagic disorders, characterized by excessive bleeding,
hemostatic mechanisms are either blunted or insufficient to
prevent abnormal blood loss.
 Thrombotic disorders -blood clots (often referred to as thrombi)
form within intact blood vessels or within the chambers of the
heart
 Involves platelets, clotting factors, and endothelium
64
 by Lami A 03/02/2025

HYPEREMIA AND CONGESTION

 Hyperemia and congestion are characterized by

locally increased blood volume.
Hyperemia
 Definition: Hyperemia is an active process in which

arteriolar dilation leads to increased blood flow to a

tissue/organ.
Causes
• Physiological: Response to increased functional
demand (e.g. heart and skeletal muscle during
exercise).
• Pathological: Seen in inflammation and is
responsible for the two cardinal signs of inflammation
namely heat (calor) and redness (rubor/erythema). 65
 by Lami A 03/02/2025

HYPEREMIA AND CONGESTION

Congestion
 Definition: Congestion is a passive process resulting

from reduced venous outflow of blood from a

tissue/organ.
Types and Causes
1. Systemic: e.g. congestive heart failure, congestion
involves liver, spleen, and kidneys.
2. Local: examples, Congestion of leg veins due to deep
venous thrombosis → edema of the lower extremity.
 Local congestion at various sites due to compression of

veins: e.g. tight bandage, plasters, tumors, pregnancy,

hernia, etc.

66
 by Lami A 03/02/2025

CONGESTION….

 Onset
1. Acute congestion: It develops during shock, or sudden
right-sided heart failure. It may occur in lung and liver.
2. Chronic passive congestion: It usually produces edema
in the organ/tissue in which the venous outflow is reduced.

67
 by Lami A 03/02/2025

EDEMA
 Definition: An abnormal accumulation
of fluid in the interstitial space within
tissues is called edema.
 Special Forms of Edema.
Terminology Body cavity involved

Hydrothorax Pleural cavity

Hydropericardium Pericardial cavity

Hydroperitoneum (ascites) Peritoneal cavity

68
 by Lami A 03/02/2025

EDEMA …
 Edema can be localized or Generalized distribution.

Local/Localized Edema

• It is limited to an organ or part (e.g. arm, leg,

epiglottis, larynx).

– Obstruction of vein or lymphatic: e.g. edema of limb

(usually the leg) develops due to venous or lymphatic

obstruction caused by thrombophlebitis, chronic

lymphangitis, resection of regional lymph nodes,

filariasis, etc. 69
 by Lami A 03/02/2025

EDEMA…
Generalized Edema

• It is systemic in distribution and affects visceral

organs and the skin of the trunk and lower extremities.

–Causes: Disorder of fluid and electrolyte metabolism.

 Heart failure

 Nephrotic syndrome (renal diseases with massive

loss of serum proteins into the urine)

 Cirrhosis of the liver

70
 by Lami A 03/02/2025

THROMBOSIS

 Definition: Thrombosis is defined as the process of

formation of a solid mass in the circulating blood
from the constituents of flowing blood.
 The solid mass formed is called as thrombus and it
consists of an aggregate of coagulated blood
containing platelets, fibrin, and entrapped cellular
elements of blood.

71
 by Lami A 03/02/2025

EMBOLISM

 Definition: An embolus is a detached

intravascular solid, liquid, or gaseous
mass that is transported in the blood to
a site distant from its point of origin.
 Thrombus
 Fat
 Air
 Amniotic fluid

72
 by Lami A 03/02/2025

Thank you
73