2. ď It is a branch of medicine which deals with any
disturbances f body functions caused by disease or
prodromal symptoms.
ď Pathology emphasizes direct observations, while
pathophysiology emphasizes quantifiable measurements.
ď Ex- Infectious disease
Pathology: Study of toxin
Pathophysiology: How does toxin cause harm
3. ďŽNormal cell is in a steady state âHomeostasisâ
ďŽChange in Homeostasis due to stimuli - Injury
ďŽInjury - Reversible / Irreversible
ďŽAdaptation / cell death
4. CELL INJURY, ADAPTATION AND DEATH
Cell Injury:
Cell injury is defined as a variety of stresses a cell
encounters as a result of changes in its internal or external
environment.
Cellular Adaptations:
When the cells are subjected to physiologic stress they
undergo certain structural and functional modifications which
are called adaptations.
Cell death:
When the stress is very severe then the cells unable to
adapt to the stress gets injured and end up as cell injury /
death.
6. CELLULAR ADAPTATION TO STRESS
Adaptations are reversible changes in the number, size, phenotype,
metabolic activity or functions of cells in response to changes in their
environment
Physiologic adaptations are responses of cells to normal stimulation by
hormones or endogenous chemical mediators
Pathologic adaptations are responses to stress that allow cells to
modulate their structure and function and thus escape injury
7. Atrophy
Shrinkage in the size of the cell by the loss of cell substance
Results from decreased protein synthesis and increased protein degradation
in cells
Causes:
a. Physiologic:
Normal function of aging in some tissues due to loss of endocrine stimulation or
arterosclerosis
Ex: atrophy of gonads after menopause, atrophy of brain, muscles etc.
b. Pathologic
Loss of innervation or neuropahtic: Poliomyelitis
Diminished blood supply: Brain in cerebral atherosclerosis
Inadequate nutrition or starvation: Protein energy malnutrition
Loss of endocrine stimulation: Hypopituitarism, hypohyroidism
Pressure atrophy: Compression of tissues for longer duration
Idiopathic: Myopathies, Testicular atrophy
8. Atrophy of the brain in an
82-year-old man
Normal brain of a 25-year-old
man
10. Hypertrophy
is an increase in the size of cells & consequently an increase in the
size of an organ.
the enlargement is due to an increased synthesis of structural proteins &
organelles
Occurs when cells are incapable of dividing
Types:
a) physiologic: Enlarged size of the uterus in pregnancy
b) pathologic:
ď§ Increased functional demand: cardiac muscle in systemic HTN,
Hemodynamic overload
ď§ Smooth Muscle: Pyloric stenosis
ď§Compensatory: Nephrectomy, Adrenal hyperplasis
14. Hyperplasia
is an increase in the number of cells in an organ or tissue
an adaptive response in cells capable of replication
a critical response of connective tissue cells in wound healing
Types:
a) Physiologic hyperplasia
1) hormonal
ex. Proliferation of glandular epithelium of the female breast at puberty &
during pregnancy
2) compensatory â hyperplasia that occurs when a portion of a tissue is
removed or diseased
e.g. partial resection of a liver > mitotic activity 12 hours later
b) Pathologic hyperplasia
Caused by excessive hormonal or growth factor stimulation
Ex: Formation of granulation tissue in wound Healing
Skin warts
15.
16.
17. Metaplasia
A reversible change in which one adult cell type ( epithelial
or mesenchymal) is replaced by another adult cell type.
It is cellular adaptation whereby cells sensitive to a
particular stress are replaced by other cell types better
able to withstand the adverse environment
Epithelial metaplasia
Examples
Squamos change that occurs in the respiratory epithelium in habitual
cigarette smokers ( normal columnar epithelial cells of trachea & bronchi
are replaced by stratified squamos epithelial cells
Vitamin A deficiency
Chronic gastric reflux, the normal stratified squamos epithelium of the
lower esophagus may undergo metaplasia to gastric columnar
epithelium
Mesenchymal metaplasia Ex. Bone formed in soft
tissue particularly in foci of injury
18. A.Schematic diagram of columnar to squamos epithelial
B. Metaplastic transformation of esophageal epithelium
19. Dysplasia:
It is a disordered cellular development
It is often accompanied with metaplasia and hyperplasia
Is most commonly occurs in epithelial cells
Characters:
Increased number of layers of epithelial cells
Disorderly arrangement of cells from basal to surface layer
Increased nucleocytoplasmic ratio
Cellular and nuclear pleomorphism
Nuclear hyperchromatism
Increased mitotic activity
20.
21. Cell Injury
Pertains to the sequence of events when cells have no
adaptive response or the limits of adaptive capability are
exceeded
Types of Cell Injury
1. Reversible Injury- injury that persists within certain limits, cells
return to a stable baseline
2. Irreversible Injury- when the stimulus causing the injury persists
and is severe enough from the beginning that the affected
cells die
22. Causes of Cell Injury
1. Hypoxia
Causes:
a. Ischemia
b. Inadequate oxygenation of the blood
c. Reduction in the oxygen-carrying capacity of the blood
2. Chemical Agents
a. glucose, salt or oxygen
b. poisons
c. environmental toxins
d. social âstimuliâ
e. therapeutic drugs
3. Physical agents- trauma, extremes of temperature, radiation, electric
shock, & sudden changes in atmospheric pressure
4. Infectious agents
23. 5. Immunologic reactions
Example: anaphylactic reaction to a foreign protein or a drug
reaction to self antigens
6. Genetic defects
Examples are genetic malformations associated with Down Syndrome,
sickle cell anemia & inborn errors of metabolism
7. Nutritional Imbalances
24. REVERSIBLE CELL INJURY
Patterns of Morphologic Change Correlating to
Reversible Injury that can be recognized under the light
Microscope are:
â˘Cellular swelling
â˘Fatty change
â˘Mucoid change
â˘Intracellular Accumulation
25. Cellular Swelling:
Increased Cellular swelling may occur due to cellular hypoxia which
damages the sodium-potassium membrane pump
It is reversible when the cause is eliminated.
Cellular swelling is the first manifestation of almost all forms of injury to
cells.
When it affects many cells in an organ, it causes some pallor,
increased turgor, and increase in weight of the organ.
Causes:
Bacterial toxins, Chemicals, poisons, Burns, High fever etc
26.
27. Hydropic degeneration: kidney
Cloudy swelling & hydropic change reflect failure of membrane
ion pumps, due to lack of ATP, allowing cells to accumulate
fluid
28. Fatty Change
â˘Cell has been damaged and is unable to adequately metabolize fat.
â˘Occurs in hypoxic injury & various forms of toxic( alcohol & halogenated
hydrocarbons like chloroform ) or metabolic injury like diabetes mellitus &
obesity manifested by the appearance of lipid vacoules in the cytoplasm
principally encountered in cells participating in and involved in fat
metabolism.
â˘Mild fatty change may have no effect on cell function; however more
severe fatty change can impair cellular function.
â˘Depending on the cause and severity of the lipid accumulation, fatty
change is generally reversible.
â˘e.g. hepatocytes & myocardial cells
29.
30. Mucoid change:
â˘mucous change:Is degeneration with accumulation of mucus in epithelial tissues
Intracellular Accumulation:
â˘It is accumulation of substances in abnormal amounts within the cytoplasm or nucleus of
the cell.
Is of 3 types:
1. accumulation of constituents of normal cell metabolism produced in excess or an
increased rate, but metabolic rate is inadequate to remove it
Ex â Accumulation of carbohydrates, lipids and proteins, Fatty change in the liver
2. Accumulation of abnormal substances produced as a result of abnormal metabolism due
to lack of some enzymes or genetic problems
Ex: Inborn error of metabolism, Accumulation of proteins in anti-trypsin deficiency
3. Accumulation of pigments or other substances because the cell has neither the enzymatic
Machinery to degrade the substance nor the ability to transport It to other sites.
Ex: melanin, carbon or silica particles
31.
32. Irreversible Cell Injury
NECROSIS
Refers to a series of changes that accompany cell death, largely
resulting from the degradative action of enzymes on lethally injured cells
The enzymes responsible for digestion of the cell are derived either from
the:
1) Lysosomes of the dying cells themselves or from
2) Lysosomes of leukocytes that are recruited as part of the inflammatory
reaction to the dead cells
Causes:
⢠Hypoxia
⢠Chemical and physical agents
⢠Microbial agents
⢠Immunological injury etc
33. Patterns of Tissue Necrosis
Coagulative Necrosis
â˘A form of tissue necrosis in which the component cells are dead but the basic
tissue architecture is preserved for at least several days
â˘It is characteristics of infarcts ( areas of ischemic necrosis) in all solid organs
except the brain
â˘The hallmark of coagulative necrosis is the conversion of normal cells into their
Tombstones ( outline of the cells are retained so that the cell type can still be
reorganised but their cytoplasmic and nuclear details are lost
A wedge-shaped kidney
Infarct (yellow) with
preserva
tion of the outlines
34. Liquefactive Necrosis
⢠Seen in focal bacterial or occassionally fungal infections because
microbes stimulate the accumulation of Inflammatory cells and the
enzymes of leukocytes digest ( âliquefyâ) the tissue
â˘This necrosis is characteristic of hypoxic death of cells witnin the CNS
â˘Associated with suppurative inflammation (accumulation of pus)
â˘The areas undergoing necrosis are transformed into Semi-solid
consistency or state (liquid viscuous mass) Example: abcess
36. Caseous Necrosis
â˘Encountered most often infoci of tuberculous infection
â˘Characterized by a cheesy yellow-white appearance of the area of necrosis
â˘It is often enclosed within a distinctive inflammatory border
â˘It combines features of both coagulative anf liquefactive necrosis
A tuberculous lung with a large
area of caseous necrosis
containing yellow-white and
cheesy debris
37. Fat Necrosis
Refers to focal areas of fat destruction, typically resulting from release of
activated pancreatic lipases into the substance of the pancreas and the
peritoneal cavity
Occurs in acute pancreatitis
Fat necrosis in acute pancreatitis. The areas of white chalky deposits represent foci of fat
necrosis with calcium soapformation (saponification) at sites of lipid breakdown in the
mesentery
38. Fibrinoid necrosis
â˘A special form of necrosis usually seen in immune reactions involving blood
vessels
This pattern of necrosis is prominent when complexes of antigens and antibodies
are deposited in the walls of Arteries
Deposits of these immune complexes together with fibrin that has leaked out of
vessels result in a bright pink and amorphous appearance called 'fibrinoidâ
Fibrinoid necrosis in an artery in a
patient with Polyarteritis Nodosa. The
wall of the artery shows a
circumferential bright pink area of
necrosis with protein deposition and
inflammation
39. Gangrenous Necrosis
⢠This is not a distinctive pattern of cell death. It is usually applied to a limb,
generally the lower leg, that has lost its blood supply involving multiple tissue layers
â˘Types:
âWet gangrene: Occurs in naturally moist areas like mouth, bowels, lungs
âCharacterized by numerous bacteria
âThe affected part appears swollen and dark.
âIt occurs mostly due to obstruction to the venous outflow
âThe line of demarcation is ill defined.
âDry gangrene: Begins at the distal part of the limb due to ischemia and often occurs in the
toes and feet of elderly patients due to arteriosclerosis
This is mainly due to arterial occlusion
There is limited putrefaction and bacteria fail to survive
The affected part appears dry, shrunken and dark to black in color. The line of demarcation is
clearly made out.
40.
41.
42. Autolysis:
Autolysis is disintegration of the cell by its own hydrolytic enzymes
liberated from lysosomes.
It occurs in the living body when it is surrounded by inflammatory
reaction or it may occur as postmortem change in which there is complete
absence of surrounding inflammatory response.
Apoptosis:
Is a form of co-ordinated and internally programmed cell death which is
of significance in a variety of physiologic and pathologic conditions.
â˘It differs from necrosis in the following characteristics
1) Plasma membrane of the apoptotic cell remains intact
2) Has no leakage of cellular contents
3) Does not elicit an inflammatory reaction in the host. Sometimes coexist with necrosis
4) Apoptosis induced by some pathologic stimuli may progress to necrosis
43. Causes of Apoptosis
Apoptosis in Physiologic Situations
ď§ Death by apoptosis is a normal phenomenon that serves to eliminate cells that are no
longer needed and to maintain a steady number of various cell populations in tissues
ď§Programmed destruction of cells during embryogenesis,Including implantation,
organogenesis, developmental, involution, and metamorphosis
ď§Involution of hormone- dependent tissues upon hormone deprivation such as endometrial cell
breakdown during the menstrual cycle and regression of the lactating breast after Weaning
ď§Death of cells that have served their useful purpose, such as neutrophils in an acute
inflammatory response and Lymphocytes at the end of an immune response
ď§Elimination of potentially harmful self-reactive lymphocytes. Either before or after they have
completed their maturation
ď§Cell death induced by cytotoxic T lymphocytes, a defense mechanism against viruses and
tumors that serves to kill eliminate virus-infected and neoplastic cells
44. Apoptosis in Pathologic Situations
Apoptosis eliminates cells that are genetically altered or Injured beyond repair
without eliciting a severe host reaction, thus keeping the damage as contained as
possible
DNA damage:Radiation, cytotoxic anticancer drugs, extremes of temperature and
even hypoxia can damage DNA either directly or via production of free radicals
Accumulation of misfolded proteins
âThese may arise because of mutations in the genes encoding these proteins or
because of extrinsic factors such as free radicals
âExcessive accumulation of these proteins in the ER leads to a condition called ER
stress