2nd Year Pathophysiology) New PDF

University of Gondar
College of Medicine & Health Sciences

School of Nursing
Department of Medical Nursing
INTRODUCTION TO PATHOPHYSIOLOGY
For 2nd Year Regular Medical Nursing Students
By Tseganesh Asefa (BSc, MSc)

11/5/19 Introduction to Pathophysiology 1
Learning Objective
 Upon completing this chapter students should be able to:
 Define common terms of pathophysiology
 Discuss the core aspects of disease in pathology
 know the diagnosis technique used in pathology

What is pathophysiology?

Physiology
Pathophysiology
Pathology

 Physiology:- a biological discipline, it describes function and
activities of living organisms and their parts.
 Pathology:- a medical discipline, it focuses on the structural,
biochemical, and functional changes in cells, and organs in
diseases state.

Pathophysiology
 Pathophysiology is a convergence of pathology with
physiology, it is the study of disorder in physiological
processes
 Pathophysiology seeks to explain the functional changes
that are occurring within an individual due to a disease or
pathologic state.
Cont.…
Disease
 Loss of homeostasis, or when physical or mental capacities
cannot be fully utilized (interruption, cessation or disorder in
the function of an organ or system).

Four aspects of a disease process/
core of cell pathology

Cont.…
1. Etiology
 The cause of the disease
 When the etiology is unknown, the disease is said to be
idiopathic.
Categories of etiology
 Genetic
 Congenital
 Acquired

Cont.…
Genetic
 Genes are responsible for a structural or functional defect
Congenital
 Genetic information is intact, but the intrauterine environment
interferes with normal development
Acquired
 Disease is caused by factors encountered after birth
(biological agents, physical forces, and chemical agents)
Cont.…
2. Pathogenesis
 Sequence of events in the of development of a disease process
 Sequela:- a pathological condition or lesions or impairments resulting
from a prior disease, injury, or attack.
Acute conditions
 Rapid onset, develop quickly, usually of short duration
Chronic conditions
 Longer duration:- onset may be sudden or insidious
Cont.…
3. Molecular and morphological change
Stressor or ethology led the molecular (biologically important

molecules such as DNA, RNA, and protein) and
morphological (alteration in structure and forms of a cell )
changes in cells.

Cont.…
4. Clinical manifestations
 Indications that the person is sick
Symptoms
 Unobservable effects of a disease reported by the patient.
E.g Pain, Fatigue…
Signs
 Observable or measurable traits. E.g Vital sign
Syndrome
 A collection of signs and symptoms that are associated with
a particular disease, conditions or disorder.
Cont.…
Diagnosis
 Identification of the specific disease
Therapy
 The treatment of the disease to either effect a cure or reduce the
patient’s signs and symptoms
Prognosis
 Prediction of a disease’s outcome
Is disease the result of cell injury/ damage?

Cell injury
 Cell injury also known as cell damage due to stressor, those
encounter cells from its internal or external environment
 Cellular response to stress vary & depends upon

1. Host factors: type of cell & tissue involved
2. Factors pertaining to injurious agent : extent & type of
cell injury

Causes of cell injury
 Genetic causes
 Acquired causes
 Hypoxia and ischemia
 Physical agents
 Chemical agents
 Microbial agents
 Immunological agents
 Nutritional derangements

Cellular responses
1. Cellular adaptations
2. Subcellular changes/ Intracellular accumulations
3. Reversible & irreversible cell injury

1. Cellular adaptations
 In case of severe stress, the narrow range of alteration in
structure & function is not sufficient, the cell undergoes an
altered but steady state.
Cell adapt to the changes
↓
Expressed morphologically
↓
Revert back to normal after the stressed is removed.

Adaptive response

Adaptive response
A. Atrophy
B. Hypertrophy
C. Hyperplasia
D. Metaplasia
E. Dysplasia
F. Anaplasia

Cont.…..
A. Atrophy:-
 Shrinkage in the size of the cell by loss of cell substance
 The number of cells are unchanged, just the reduction in the
size of the cell, that lead the entire tissue or organ diminishes
in size, or becomes atrophic.
 Atrophy occur due to the loss of the normal stimulus/
stressor to cell/ organ

Cont.…..
Atrophy can be physiologic or pathologic
 Physiologic atrophy is occur due to normal stressor.
 The uterine decrease in size shortly after parturition.

 Pathologic atrophy is occur due to abnormal stressor.

Cont.…..
Common causes of pathological or physiological atrophy:
1. Decreased workload (atrophy of disuse)
Examples
 Skeletal muscle atrophy due to
 Immobilized broken limb in a plaster cast
 Patient is restricted in to bed rest
 The initial rapid decrease in cell size is reversible once activity
is resumed.

Cont.…..
2. Loss of innervation (denervation atrophy)
 Normal function of skeletal muscle is dependent on its
nerve supply.
 Damage to the nerves leads to rapid atrophy of the muscle
fibers

Cont.…..
3. Diminished blood supply
 A decrease in blood supply (ischemia)
due to arterial occlusive disease results
atrophy of tissue due to progressive cell
component loss, by autophagy.
 In late adult life, the brain undergoes
progressive atrophy, because of
atherosclerosis, which narrows blood
supply

Cont.…..
4. Inadequate nutrition
 Protein-calorie malnutrition (marasmus) associated with
depletion of adipose store results marked muscle wasting
(cachexia)
 Other causes of cachexia- chronic inflammatory diseases,
cancer
5. Pressure due to long continued pressure on a tissue leading to
decrease in it is blood that cause atrophy.
E.g. Amyloidosis of liver:- the deposition of protein or amyloid
on liver  ischemia  liver atrophy
Cont.…..
6. Loss of endocrine stimulation
 The loss of estrogen stimulation after menopause results in
physiologic atrophy of the endometrium , vaginal epithelium,
and breast.
7. Aging (senile atrophy)
The aging process is associated with cell loss, typically seen in
tissues containing permanent cells, particularly the brain and
heart.

Cont.…..
B. Hypertrophy
 An increase in the size of cells, resulting in an increase in the
size of the organ ( without any change in the number of cells)
 Hypertrophied organ has no new cells ,just large cells.
 Due to synthesis of more cellular components, it is not cellular
swelling.
 Hypertrophied Nuclei:- a higher DNA content than in normal
cells, probably because the cells arrest in the cell cycle without
undergoing mitosis.

Cont.…..
 Hypertrophy can be caused by due to

 Increased functional demand
 Specific hormonal stimulation

Cont.…..
Hypertrophy can be physiologic or pathologic
Physiological hypertrophy
 Skeletal muscle hypertrophy with sustained weight bearing exercise
 Increase in the size of uterus during pregnancy due to hormone, it
might be accompanied by hyperplasia
Pathological hypertrophy
 Cardiac muscle as a result of hypertension

Cont.…..
C. Hyperplasia
 An increase in number of cells in an organ or tissue resulting in
enlargement of the organ or tissue.
Hyperplasia and hypertrophy may occur by same external stimuli.
Example:
 Hormone-induced growth in the uterus involves both increased
numbers of smooth muscle and epithelial cells and the
enlargement of those cells.
 RBC hyperplasia occurs with out hypertrophy

Cont.…..
Hyperplasia can be physiologic or pathologic.
I. Physiologic hyperplasia can be divided into:
 Hormonal hyperplasia- which increases the functional capacity
of a tissue when needed
Eg. Female breast at puberty and during pregnancy
Uterine hyperplasia that occurs in pregnancy
 Compensatory hyperplasia- which increases tissue mass after
damage or partial resection.
Eg. Liver after partial hepatectomy
Unilateral kidney after nephrectomy
Cont.…..
Pathological hyperplasia: cellular proliferation/ Hyperplasia
occur due to abnormal stressor such as:
 The production of local growth factor,
 Growth factor receptors on responding cells
 Activation of intracellular signaling pathways
Example:
 Endometrial hyperplasia:- Absolute or relative increases in
the amount of estrogen => abnormal menstrual bleeding.
 Benign prostatic hyperplasia:- due to cell sensative
response to Anderogen hormone
Cont.…..
D. Metaplasia
 One adult cell type replaced by another adult cell type.
 Substitution of cells that are sensitive to stress by another cell
which has a better able to withstand the adverse environment.
 The most common example is epithelial metaplasia:-
The replacement of columnar epithelial cells by squamous
epithelial cells.

Cont.…..
Examples:
 In cigarette smoker  the cigarette chemicals are stressor, the
normal ciliated columnar epithelial cells can't tolerate the stress
so it is replaced by stratified squamous epithelial cells.
 Stones in the excretory ducts of the salivary glands, pancreas, or
bile ducts  replacement of the normal secretory columnar
epithelium by nonfunctioning stratified squamous epithelium.

Cont.…..
E. Dysplasia
 A pre cancer, or atypical hyperplasia.
 Disordered growth and maturation of cell
 Recognizable morphologic changes in cells that indicate the
presence of genetic mutations beginning the development of a
neoplasm.

Cont.…..
F. Anaplasia
 Recognizable morphologic changes in cells that lack of
differentiation (resemblance to normal cell)
 Implies the presence of advanced cancer, or undifferentiated
cells.

Cont.…..
Features of anaplasia:-
 Pleomorphism:- variation in size & shape of cytoplasm & nucleus.
 Abnormal nuclear change:- the DNA particle increase and lead
staining which is called hyperchromatic nucleus.
 Nuclear cytoplasmic ratio become 1:1.
Note:- Normal cell nucleus to cytoplasm ratio = 1:4 or 1: 6
 Presence of giant cell: enlarge cell contain large nucleus or multiple
nucleus different from all other giant cell.
Note: Normal giant cell such as lung or foreign body cell
 Loss of polarity: arrange in haphazard manner.
2. Subcellular changes/ Intracellular accumulations
 Sublethal or chronic stimuli/ stressor may induce a variety of

subcellular alterations or changes in cells/ tissues other than
adaptations and death.
 Metabolic derangements and abnormal substance accumulate
in side the cells  evidence of cell injury.

Cont.…..
A normal cellular constituent- water, lipid, proteins &
carbohydrates.
An abnormal substance
 Exogenous : minerals or products of infectious agents
 Endogenous: products of abnormal synthesis or metabolism
 Pigments- lipid accumulation either Tigroid or diffuse

3. Reversible & Irreversible cell injury
 Cell injury:- cell’s adaptive capability is exceeded or if

adaptive response is not possible, cell injury develops.
Two types
I. Reversible cell injury ( Degeneration ):stress is
mild to moderate ; injured cell may recover.
II. Irreversible cell injury ( Necrosis ) : Persistent &
severe form of cell injury leads to cell death.

Cont.…..
Depends:
Small doses of a chemical toxin for brief periods may induce

reversible injury
Large doses of the same toxin for more prolonged period
result instantaneous cell death or in slow, irreversible injury
leading in time to cell death.
Cont.…..
Depends:
 The striated muscle cell in the leg can tolerate a deprived blood
supply; not so the striated muscle of the heart.
Note:- Exposure of two individuals to identical concentrations of a toxin,

such as carbon tetrachloride, may not produce effect in one and cell
death in the other. This due to genetic variations affecting the amount
and activity of hepatic enzymes that convert carbon tetrachloride to toxic
byproducts
I. Reversible cell injury (RCI)
The pathogenesis of RCI:-
 Ethology's =>
 Ischemia =>
 Hypoxia =>

Cont.…
Alteration in tissue oxygenation
Ischemia is inadequate blood supply to a cell or tissue, cause
hypoxia.
Hypoxia = deficiency in oxygen at cell
Due to :
 Decreased oxygen in air
 Decreased hemoglobin or decreased oxygen transported
to cells
 Diseases of the respiratory and/or cardiovascular system

Cont.…..
Hypoxia  Effect on oxidative phosphorylation by

mitochondria  ↓ ATP production  anaerobic
glycolysis  ↓ glycogen level  ↑ lactic acid 
↓ intracellular PH  Clumping of nuclear
chromatin

Cont.…..
Hypoxia  effect on oxidative phosphorylation by
mitochondria  ↓ATP production  Na-K Pump stops 
more Na inside  cell becomes hyperosmolar  water

enters  Cellular swelling  bleb formation 
ribosomes detach.
Cont.…..
 ↓ O2 supply  anaerobic glycolysis and fat/ lipid
metabolism  appearance of small or large lipid
vacuoles in the cytoplasm  Fatty Change
Note: Fatty change most commonly occur in cells which

normally metabolize large amount of fat like renal tubular
epithelia cells and hepatocytes

Cont.…..
Abnormal accumulations
 Lipid
 Protein

Cont.…..
 Cellular swelling 
 Hydropic swelling/ dilation of ER 
 Ribosomes detached from ER
Hypoxia continues  Polysomes degraded to monosomes 
 ↓ intracellular protein synthesis 
 Cytoskeleton changes:- loss of microvilli
and formation of blebs
Ultra structural changes of RCI
1) Swelling and appearance of phospholipid – rich
amorphous densities in mitochondria
2) Nuclear alterations with clumping of chromatin
3) Dilation of endoplasmic reticulum
4) Detachment of ribosomes
5) Blebbing of plasma membrane
6) Blunting or distortion of microvilli
7) Loosening of intercellular attachments
II. Irreversible cell injury
2 essential features:
 Inability of the cell to reverse mitochondrial dysfunction
 Disturbance in cell membrane function
In addition:
 Depletion of proteins,
 Leakage of lysosomal enzymes into cytoplasm,
 Reduced intracellular pH and
 Further reduction in ATP.

Morphology of irreversible cell injury
(cell death)
 Cell death is a state of irreversible injury, it may occur as:
A. Local or focal change
1. Autolysis
2. Necrosis and
3. Apoptosis
B. Changes that follow
1. Gangrene and
2. Pathologic calcification
C. End of life ( somatic death)
Cont.…..
1. Autolysis/ self digestion:-
 Disintegration of the cell by its own hydrolytic enzymes
liberated from lysosomes
 Morphologically , autolysis is identified by :
 Homogeneous and eosinophilic cytoplasm
 Loss of cellular details
 Remains of cell as debris

Cont.…..
2. Necrosis:-
 The result of protein denaturation and degradation of
tissue by hydrolytic enzymes liberated from lethally
injured cells, accompanied by inflammation.
 2 essential features:
 Cell digestion by lytic enzymes
 Denaturation of proteins

Cont.…..
 Necrotic cells are unable to maintain membrane integrity
and their contents often leak out. This may elicit
inflammation in the surrounding tissue.

Cont..…
Morphologic change in necrosis, by electron microscopy
Cytoplasmic
 Overt discontinuities in plasma and organelle membranes
 Marked dilation of mitochondria with the appearance of large
amorphous densities
 Intracytoplasmic myelin figures, amorphous osmiophilic
debris, and aggregates material probably representing
denatured protein 65
Cont.…..
Nuclear
 Pyknosis- Shrinkage/ condensation of nuclear chromatin
 Karyolysis – undergo dissolution/ loss of DNA because
of enzymes
 Karyorrhexis- fragmentation into many clumps

Types of necrosis
1. Coagulative Necrosis
2. Liquefactive Necrosis
3. Caseous Necrosis
4. Fat Necrosis
5. Fibrinoid Necrosis
6. Gangrenous Necrosis

Cont.…..
1. Coagulative necrosis
o Most common type necrosis
o Mostly from sudden cessation of blood flow (ischemia) and less
often from bacterial and chemical agents
o Formation of gelatinous (gel-like) substance in dead tissue 
maintained/ preserve tissue for some days.
o Denaturation of protein, causing albumin to transform in to a
firm and opaque state.
Cont.…..
o In early stages: tissues exhibit a firm, pale, and slightly
swollen texture
o With progression: become more yellowish, softer, and
wasted.
o All organs affected except brain
o Ultimately the necrotic cells are removed by phagocytosis of
the cellular debris by infiltrating leukocytes.
Cont.…..
2. Liquefaction (colliquative) necrosis
o Commonly occurs due to ischemic injury and bacterial or
fungal infections.
o It occurs due to degradation of tissue by the action of
powerful hydrolytic enzymes or
o The digestion of the dead cell, transform the tissue into a
liquid viscous mass.
Cont.…..
o The necrotic material is frequently creamy yellow
because of the presence of dead leukocytes and is called
pus.
o Common eg. Infarct brain and abscess cavity.

3. Caseous necrosis Cont.…..
o “Caseous” (cheese like), the necrotic tissue
appears as white and friable, like clumped

cheese.
o The dead cells disintegrated but not completely
digested, and amorphous granular debris enclosed
within a distinctive inflammatory border.
o It is a combined feature of coagulative and
liquefactive necrosis.
Cont.…..
4. Fatty necrosis
o Hydrolysis of neutral fat present in
adipose cells into glycerol and free fatty
acids.
o Free fatty acids can combine with
calcium produce grossly visible chalky-
white areas (fat saponification).

Cont.…..
o A special form of cell death occurring at two anatomically
different locations but morphologically similar lesions.
o These are:
 Following pancreatic necrosis
 Traumatic fat necrosis commonly in breast

Cont.…..
5. Fibrinoid necrosis
o Characterized by the deposition of fibrin like material
o A special form of necrosis caused by immune mediated
vascular damage.
o It is marked by deposits of “immune complexes,” together with
fibrin that has leaked out of vessels.
o (eg. Autoimmune diseases, arthus reaction), artioles in
hypertension, peptic ulcer etc
?
 Coagulative necrosis is not common in……………
A. Kidney
B. Heart
C. Brain
D. Adrenal gland
11/5/19 Clinical Grading and Staging 77

Cont.…..
Answer:- Brain
Which type of necrosis is common in brain?
Why? Coagulative necrosis is not common in

brain.

Cont.…..
Brain contains little connective tissue but high amount of
digestive enzyme, during necrosis the digestion of dead cells
form a viscous liquid mass.

Cont.….
3. Apoptosis
 A form of ‘coordinated and internally programmed cell
death’ which is of significance in variety of physiologic
pathologic conditions.

Cont.….
Physiological Apoptosis
Embryonic notochord  during embryogenesis.
Endometrial cell breakdown  during the menstrual cycle
Ovarian follicular atresia  menopause
Regression of the lactating breast  after weaning

Cont.…..
Pathological Apoptosis
Cell death produced by a variety of injurious stimuli.

 Radiation and cytotoxic anticancer drugs damage DNA
 Heat and hypoxia, can induce apoptosis if the insult is
mild
 Viral diseases, such as viral hepatitis, in which loss of
infected cells is largely because of apoptotic death.
Cont.…
Morphological changes
1) Cell shrinkage
2) Chromatin condensation
3) Fragmentation
4) Phagocytosis of apoptotic bodies by macrophages

Cont.…..
1) Cell shrinkage: the apoptosis begins when the nucleus of the
cell begins to shrink, that lead the aggregation of chromatin
under the nuclear membrane which is called Chromatin
condensation
2) Formation of cytoplasmic blebs:- plasma membrane form

blebs and fold around organelle which results extensive
surface blebbing
Cont.…..
3) Fragmentation: The nucleus itself may break up, produce
fragments, and the blebs continue to form fragmented
organelles and move away from one another.
4) Phagocytosis of apoptotic bodies by macrophages

Cont.…..
Mechanisms of Apoptosis
The process of apoptosis can be initiated through one of two pathways:

Intrinsic pathway: the cell kill itself because it senses stress.
 Extrinsic pathway: the cell kill itself because of signals from other
cells.
Note: Weak external signal may activate the intrinsic pathway

apoptosis
Cont.…..
Gangrene
 Gangrene is a potentially life-threatening condition caused
by a critically insufficient blood supply (necrosis).
 The primary cause of gangrene is reduced blood supply to
the affected tissues, which results in cell death.
 3 types of gangrene:- Dry, Wet & Gas

Cont.….
Dry gangrene
 A form of coagulative necrosis that develops in ischemic
tissue, where the blood supply is inadequate to keep tissue

viable.
 The limited oxygen in the ischemic limb that limits decay and
bacteria fail to survive.

Cont.…..
Wet gangrene
 Usually develops rapidly due to blockage of venous (mainly)
and/or arterial blood flow.
 The affected part is saturated with stagnant blood, which
promotes the rapid growth of bacteria

Cont.…..
Gas gangrene
A bacterial infection that produces gas within tissues.
Caused by bacteria producing exotoxin like Clostridium

Senescence
 A state of irreversible growth arrest
 A permanent state of cell cycle arrest
 Senescence/ a biological aging is the gradual deterioration

of functional characteristics

???
How the body continue the function/
structure if the injured cell going to die

University of Gondar
College of Medicine & Health Sciences
School of Nursing
Department of Medical Nursing
TISSUE REGENERATION AND REPAIR
By Tseganesh Asefa (BSc, MSc)
11/5/19 Tissue Regeneration and Repair 95

Cont.…
 Injury  cell death and tissue destruction  disruption of
the anatomic structure and function in any body part 
wound
 Wound healing is a body response mechanism to injury in
an attempt to restore the normal structure and function .
11/5/19 Tissue Regeneration 96

Cont.…
Healing involves 2 distinct processes :
 Regeneration:- replacement of the injured cells by the
same type cells from it is precursor/ ancestor
 Repair:- replacement of injured cells by connective
tissue, that leave scar or fibrosis
At a times both processes take place simultaneously

Tissue regeneration
Tissue regeneration:- the replacement/ healing occur by
proliferation of parenchymal cell & complete restoration of
damaged tissue.
 What is parenchymal cell?
 Any organ are two parts:- Functional and Structural

 Parenchymal :- functional cells
 Stromal :- structural supporting connective tissue, vessels,
nerve fiber and extracellular matrix.
Cont.…
 Regeneration is the process of renewal, restoration, and growth
that makes genomes, cells, organs, organisms, and ecosystems
resilient to natural fluctuations or events that cause disturbance
or damage.
 Every species is capable of regeneration, from bacteria to
humans.
 What happen if their is no regeneration?
If there is no regeneration in nature, there would be
no life either!

Cont.…
 The most impressive samples
for regeneration in nature is
the regrowth of lizards’ and
salamenders’ leg and tail.
 Nerves, muscles, skin, bone
and vessels in other words all
the tissues are regenerated.
Cont.…
 Humans have limited regeneration ability.
 The skin/ epidermis can regrow but can’t regenerate the

nerve cells ,bones, or tendons.
 All the organ tissues can regrow but it’s very limited except
the liver.

Cont.…
 The liver is the only internal
human organ capable of natural
regeneration of lost tissue; as
little as 25% of a liver can
regenerate into a whole liver.
 Compensatory regeneration

Cont.….
Regeneration ability of organ depends on
1. The cell cycle and proliferative capacity of parenchymal

cells.
2. Growth factors
3. The intactness of ECM

1- Cell cycle and the proliferative capacity of
parenchymal cells
Cells are of 3 types
depending on their
capacity to divide :
 Labile cells
 Stable cells
 Permanent cells
Cont.…
1. Labile cells (continuously dividing & continuously dying),
continuous cycle from one mitosis to next. e.g. Stem cells
such as
 Epithelial tissue of Skin
 GIT epithelium, oral and vagina cells
 Bone marrow cells

Cont.…
Liable cell/ stem cells incompletely
differentiated through the life.
 Self renewal capacity
 Asymmetric replication
• One differentiated, one remain
undifferentiated
 Differential potential/ capacity to develop
into multiple lineages
• Multipotent- e.g. Hematopoietic cells-
become RBCs, WBCs, or Platelets
 Extensive proliferative potential
Cont.…
2. Stable cells :- quiescent cells in the Go stage neither cycling nor
dying cells and can be induced to re-entered in the cycle by an
appropriate stimuli
 Capable to proliferate in response to injury. Examples:
 Parenchyma of most solid tissue (Liver, kidney & pancreas )
 Vascular endothelial cell
 Fibroblast and Smooth muscles.
Cont.…
3. Permanent cell:- a non dividing, non proliferated cells in
postnatal life.
 Cells existed from cell cycle and distended to die with out
further division.
Examples:- Neurons, cardiac muscle, and skeletal muscle.

Cont.…
NOTE:-
 If the damage occur in Liable/ stable cell  healing by
regeneration.
 If damage occur in permanent cell  healing by repair/ non
functional fibrous scar tissue.

2- Growth factors
 A growth factors are a proteins or steroid hormones that
binding to specific receptors on the cell surface or
intracellularly and stimulate cell growth, proliferation, or
healing.

Signaling mechanisms of growth factor receptors
1. Autocaine signaling : acts on the cell that secretes it.
2. Paracaine signaling: affects cells in the immediate neighborhood

of the cell that released the agent.
 This pathway is important for recruiting inflammatory cells to the
site of infection and for wound healing.
3. Endocrine signaling: a regulatory sub-stance, such as hormone, is

released into the bloodstream & acts on target cells at a distance.
3- Extracellular matrix
 ECM regulates the proliferation, movement, and differentiation of
the cells living within it.

 An intact ECM is required for tissue regeneration, and if the ECM
is damaged, repair can only be accomplished by scar formation.
 ECM have to basic forms:
1. Interstitial Matrix
2. Basement Membrane
Cont.…
1. Interstitial Matrix:- the spaces between cells in connective
tissue, and between epithelium and supportive vascular and
smooth muscle structures.
 It is synthesized by mesenchymal cells (e.g., fibroblasts)
 Its contains: *fibrillar and nonfibrillar collagens
*fibronectin *elastin *proteoglycans *hyaluronate

Cont.…
2. Basement Membrane: array/ arrangement of interstitial
matrix in connective tissues becomes highly organized
around epithelial cells, endothelial cells, and smooth
muscle cells.
 It contains: collagen , Adhesive glycoproteins, and Laminin

Roles of the Extracellular Matrix
 Establishment of tissue microenvironments
 Scaffolding/ framework for tissue renewal: injury to the

tissues results in restitution of the normal structure only if the
ECM is not damaged
 Mechanical support for cells and cell migration/ relocation
 Control of cell growth

Cont.…
 Maintenance of cell differentiation
 Storage and presentation of regulatory molecules. For

example, growth factors like FGF and HGF are excreted and
stored in the ECM in some tissues.
 Disruption of these structures leads to collagen deposition
and scar formation

Components of the Extracellular Matrix
1. Fibrous structural proteins such as collagens and elastins,

which confer tensile strength and recoil
2. Water-hydrated gels such as proteoglycans and hyaluronan,

which permit resilience and lubrication
3. Adhesive glycoproteins that connect the matrix elements to

one another and to cells
Liver Regeneration
Regeneration of the liver occurs by two major mechanisms:

 Proliferation of remaining hepatocytes
 Repopulation from progenitor cells.

Proliferation from remaining hepatocytes
Hepatocyte proliferation in the regenerating liver is triggered by
the combined actions of cytokines and polypeptide growth
factors.
It has 3 phases.
1. Initiation/ Priming phase

2. Promotion/ Growth factor phase
3. Termination phase
Cont.…
1. Initiation or priming phase:- Kupffer cells produce a
cytokines such as IL-6  make the hepatocytes parenchymal
cells to receive and respond signals to growth factor.
2. Proliferation or growth factor phase:- primed hepatocytes

receive growth factors such as HGF and TGF-α,  stimulate
cell metabolism and entry of the cells into the cell cycle.

Cont..
Note:- Because hepatocytes are quiescent cells, it takes several
hours to enter the cell cycle, progress from G0 to G1, and
reach the S phase of DNA replication.
 Almost all hepatocytes replicate during liver regeneration.
3. Termination phase:- Hepatocytes return to quiescence.

Liver regeneration from progenitor cells
 Proliferative capacity of primed hepatocytes is impaired, due to chronic
liver injury or inflammation.
 Progenitor cells in the liver going to repopulation.
 Progenitor cells is like stem cell:- tendency to differentiate into specific

type of cell or pushed to differentiate into its “target” cell.
 The difference b/n stem and progenitor cell:- stem cell replicate
indefinitely whereas progenitor cells divide only a limited number of
times.
Summary
Cell and tissue regeneration:- the replacement of injured tissue
by same type of original tissue cells. This can be determined by :-
 Labile & stable cells
 Involves two tissue components: Cellular proliferation,
regulated by growth factors & growth inhibitors.
 An intact ECM & cell-matrix interaction
 An intact basement membrane directs epithelial cell polarity
& is essential for its orderly regeneration
 Unless injured tissue replaced by connective tissues that is
called Repair.
Thank You
for
Your Attention!!!
11/5/19 Hemodynamic Disorder 127
11/5/19
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Tissue Regeneration 128

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University of Gondar

College of Medicine & Health Sciences

For 2nd Year Regular Medical Nursing Students

By Tseganesh Asefa (BSc, MSc)

11/5/19 Introduction to Pathophysiology 2

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3. Molecular and morphological change

Stressor or ethology led the molecular (biologically important

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 Cellular response to stress vary & depends upon

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 The uterine decrease in size shortly after parturition.

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 Hypertrophy can be caused by due to

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 Sublethal or chronic stimuli/ stressor may induce a variety of

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 Cell injury:- cell’s adaptive capability is exceeded or if

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Small doses of a chemical toxin for brief periods may induce

Note:- Exposure of two individuals to identical concentrations of a toxin,

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Hypoxia  Effect on oxidative phosphorylation by

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Hypoxia  effect on oxidative phosphorylation by

mitochondria  ↓ATP production  Na-K Pump stops 

more Na inside  cell becomes hyperosmolar  water

Note: Fatty change most commonly occur in cells which

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