Unit 2 Part 2 Flashcards
Study of disease
Pathology
infection, genetic etc. and often mutifactoral
Etiology of cause
Progression of disease
Pathogenesis
Signs and symptoms
Clinical manifestations
Pathology 4 studies
Etiology
Pathogenesis
Molecular and morphologic changes
Clinical manifestations
Structural and functional units of tissues and organs
Cells
Capable of adjusting their structure and functions in response to physiological and pathological conditions
Cell adaptation
New steady state
Preserving viability
Adaptation
Cell poliferation (3 variables)
Labile
Stable
Permanent
Continously dividing
Labile cells
Labile cells example
Epithelium
Bone marrow
Hematopoietic cells
Quiescent
In g0 stage
Stable cells
Stable cells example
Hepatocytes
Smooth muscle
Lmphocytes
Nondividing
Permanent cells
Permanent cells example
Neurons
Skeletal and cardiac muscle
Types of adaptations are conrolled by
Complex molecular mechanisms
Types of cellular adaptation
Hypertrophy
Hyperplasia
Atrophy
Metaplasia
Dysplasia*
normal stressor/stimuli; results in enhanced function
Phsyiologic adaptation
abnormal stressor/stimuli; results in dysfunction and mortality
Pathologic
adaptation to positively counteract reduction in function
Compensatory adaptation
Increase in size; organ enlargement
No new cells
Increase in mrna and proteins
Hypertrophy
in response to increased demands
seen in cells that cannot divide
changes usually revert to normal if cause is removed
Hypertrophy
Gym body
Physiologic hypertrophy
Heart of patient with long standing hypertension
Pathologic hypertrophy
Increased number of cells
Co-exist with hypertrophy
Takes place IF cell if capable of replication
Hyperplasia
Female breast in puberty and pregnancy
Physiologic hyperplasia
Excessive hormonal stimulation
Pathologic hyperplasia
Hypertrophy and hyperplasia example
Gravid uterus during pregnancy
Loss of substance-Shrinkage in the size of cell
Sufficient number of cells is involved
Entire tissue or organ diminishes in size
Not dead
Atrophy
Atrophy results from both
Decreased protein synthesis
Increased protein degradation
Lysosomes with hydrolytic enzymes
Ubiquitin-proteasome pathway
Increased protein degradation
Brain atrophy
Uterus atrophy
Physiologic atrophy
Inadequate nutrition (malnutrition)
Diminished blood supply
Pathologic atrophy
-Reversible change
-Adult cell type is replaced by another cell type for adverse envi
-occurs in response to stress or chronic irritation
Metaplasia
Mechanisms of metaplasia
Re-programming of stem cells
Induced by cytokines, growth factors, envi signals
Retinoic acid may play a role
Unknown exact mechanism
Metaplasia SOM
Squamous
Osseous
Myeloid
Cigarette smoking
Gastroesophageal reflux disease
Glandural epithelium
Squamous metaplasia
TRUE OF FALSE
Atrophy, hypertrophy, hyperplasia, and metaplasia are reversible changes
TRUE
TRUE OR FALSE
Hyperplasia and Metaplasia are not premalignant changes
TRUE
Fertile fields for dysplasia
Hyperplasia and metaplasia
Atypical proliferative changes
due to chronic irritation or inflammation
Cells vary in size and shape
Large nuclei
Increased rate of mitosis
Premalignant change
Dysplasia
Cells are undiferrentiated w nuclear and cell structures and mitotic figures
Cancer and tumor is the basis for grading its aggressiveness
Anaplasia
New growth
Tumor
Neoplasia
Less serious cancer cells
Do not spread and are not life threatening (except in the brain)
Benign
Progressive cancer cells
Malignant
Failure of cell production
During fetal development, it results to agenesis
Aplasia
Absence of an organ due to failure of production
Agenesis
Incomplete development of an organ
Decrease in cell production
Hypoplasia
Examples of hypoplasia
Hypoplastic left ventricle
Hypoplastic kidney
control the composition of their immediate environment and intracellular milieu within a narrow range of physiological parameters
homeostasis
denotes pathologic changes that can be reversed when the stimulus is removed, or if the cause of injury is mild
Reversible cell injury
denotes pathologic changes that are permanent and cause cell death
Irreversible injury
oxygen deprivation
Hypoxic Cell injury
loss of blood supply
more rapidly and severely injures
Ischemia
cardiorespiratory failure
Inadequate oxygenation
anemia, carbon monoxide poisoning
Loss of oxygen carrying capacity of blood
Causes of Cellular Injury
Hypoxic Cell injury
a. Ischemia
b. Inadequate oxygenation
c. Loss of oxygen carrying capacity of blood
High Susceptibility of Cells to Hypoxic Injury
Neurons (3-4 min)
Intermediate Susceptibility of Cells to Hypoxic Injury
Myocardium, hepatocytes, renal epithelium (30 min-2hr)
Low susceptibility of cells to hypoxic injury
Fibroblasts, epidermis, skeletal
muscle (many hours)
ROS
Hydroxyl, Hydrogen, Superoxide
-with a single unpaired electron in an outer orbital
-Chemically unstable=chemical damage
- Initiate autocatalytic reactions
Free Radical Injury
If not adequately neutralized, free radicals
can damage cells by
Lipid peroxidation of membranes
DNA fragmentation
Protein cross-linking
double bonds in polyunsaturated
membrane lipids are vulnerable
Lipid peroxidation of membranes
react with thymine in nuclear and mitochondrial
DNA fragmentation
promote sulfhydryl-mediated protein cross
linking
Protein cross-linking
Neutralization of Free Radicals
SpoSuGCaEn
- Spontaneous decay
- Superoxide dismutase
- Glutathione (GSH)
- Catalase
- Endogenous and exogenous antioxidants
(Vitamins E, A, C and β carotene)
cellular injury trauma, heat, cold,
radiation, electric shock
physical agents
-Therapeutic drugs - paracetamol
-Nontherapeutic agents – lead, alcohol
-Binding of mercuric chloride to sulfhydryl
groups of proteins
-Generation of toxic metabolites such as
conversion of CCl4 to CCL3* free radicals in
the SER of the liver
Chemical Agents
Causes of Cellular Injury
Infectious Agents
ViBaFuRiBaFuPa
a) Viruses
b) Bacteria
c) Fungi
d) Rickettsiae
e) Bacteria
f) Fungi
g) Parasites
direct effects of
bacterial toxins; cytopathic effects of
Infectious agents
-interfering with DNA,RNA, proteins, cell
membranes or
-inducing apoptosis.
-indirect effects via the host immune reaction.
infectious agents
anaphylaxis, loss of
immune tolerance leading to autoimmunity
Immune System -
sickle cell
disease, inborn errors of metabolism
Genetic Abnormalities
vitamin deficiencies, obesity leading to type II DM, fat leading to atherosclerosis
Nutritional imbalances
degeneration as a result of
trauma, intrinsic cellular senesence
Aging
causes of cell injury
Hypoxic Cell injury
Free Radical Injury
Physical Agents
Chemical Agents
Infectious Agents
Immune System
Genetic Abnormalities
Nutritional imbalances
Aging
2 ways of cell death
necrosis
apoptosis
-produced by enzymatic digestion of dead
cellular elements
-irreversible injury
necrosis
eliminate unwanted cells–an internally programmed series of events effected
Apoptosis
-Morphologic expression of cell death
-disintegration of cell structure
-initiated by overwhelming stress
-elicits an acute inflammatory cell
response
Necrosis
types of necrosis
CoLiCaGaFiFa
coagulative
liquefactive
caseous
gangrenous
fibrinoid
fat
seen in hypoxic environments
the outline of the dead cells are maintained the tissue is somewhat firm.
◼Example: myocardial infarction
Coagulative necrosis
dead cells undergo disintegration and affected tissue is liquified
associated with cellular destruction
and pus formation
ischemia in the brain
Example: cerebral infarction
Liquefactive necrosis
ischemia
restriction of blood supply
form of coagulation (cheese-like)
caused by mycobacteria
Example: tuberculosis lesions.
Caseous necrosis
(secondary to ischemia)
usually with superimposed infection
Example: necrosis of distal limbs, usually foot
and toes in diabetes.
Gangrenous Necrosis
(secondary to ischemia)
usually with superimposed infection
Example: necrosis of distal limbs, usually foot
and toes in diabetes.
Gangrenous Necrosis
by immune-mediated vascular damage.
by deposition of fibrin-like proteinaceous material in arterial walls
smudgy and eosinophilic
Fibrinoid necrosis
by immune-mediated vascular damage.
by deposition of fibrin-like proteinaceous material in arterial walls
smudgy and eosinophilic
Fibrinoid necrosis
release of powerful enzymes which damage fat by the production of soaps
chalky white
fat necrosis
release of powerful enzymes which damage fat by the production of soaps
chalky white
fat necrosis
fat necrosis types
Traumatic fat necrosis
Enzymatic fat necrosis
necrosis of fat by pancreatic enzymes.
Enzymatic fat necrosis
is restricted to necrosis involving spirochaetal infections (e.g. syphilis).
Gummatous necrosis
blockage of the venous drainage (e.g. in
testicular torsion).
Haemorrhagic necrosis
-Regulated suicide program
-Controlled by specific genes.
-Fragmentation of nucleus, DNA
-Blebs form and apoptotic bodies are released.
-Apoptotic bodies are phagocytized.
-No neutrophils.
Apoptosis
n cells produced =n cells die
Development and morphogenesis
Homeostasis
Deletion of damaged/ dangerous cells
apoptosis
During limb formation separate digits evolve
Ablation of cells no longer needed (tadpole)
Apoptosis: Development and morphogenesis
Immune system
>95% T and B cells die during maturation
(negative selection)
apoptosis: Homeostasis
Examples of Apoptosis
removal of excess cells during embryogenesis
maintain cell population (skin)
eliminate immune cells
remove damaged cells
eliminate cells with DNA damage
Hormone-dependent involution
Cell death in tumours.
causes of apoptosis
◼ Physiologic
◼ Pathologic
Physiologic Apoptosis
Embryogenesis and fetal development
Hormone dependent involution - mens
Cell loss in proliferating cell populations
Elimination of self-reactive lymphocytes
Death of cells
programmed cell destruction in
embryogenesis
Pathologic Apoptosis
DNA damage due to radiation
misfolded proteins
viral infections hiv
Organ atrophy after duct obstruction
