-
Adaptation
-
Atrophy
- ↓cellular size
-
Physiologic atrophy
- e.g. Thymusgland
-
Pathologic atrophy
- ↓workload, pressure, blood supply, nutrition, hormonal stimulation and nervous stimulation
- Immobilization- disuse atrophy
- Aging- brain cells and endocrine- dependent
-
cellular properties
- Less endoplasmic reticulum
- Fewer mitochondria and myofilaments
- Decrease protein synthesis
-
Increase protein catabolism
- Pathway
- Ubiquitin- proteosme pathway
- protein are first conjugated to ubiquitin
Degrade within a large cytoplasmic proteolytic
complex or proteosome
- Metabolic acidosis
- Glucocorticoids
- Thyroid hormone
- Chronic malnutrition
- Autophagic vacuoles
- Membrane
- Destroyed by lysosomes
- Lipofuscin
-
Hypertrophy
-
↑cellular size & organ size
by ↑protein in the cellular components
-
Physiologic hypertrophy
- ↑workload
-
Compensatory hypertrophy
- e.g. kidney
-
Pathologic hypertrophy
- e.g. hypertension
-
Hyperplasia
-
mitotic division occur
↑ number of cell by:
- Increased workload
- Hormonal stimulation
- Decrease tissue density
-
Physiologic
- e.g. endometrium
- Breast and uterine...pregnancy
-
Compensatory
- regeneration of the liver after partial hepatectomy
-
Pathologic
- Excessive hormone stimulation
-
Metaplasia
- Reversible change of one cell type with another cell type
- Reprogramming of undifferentiated stem cells
-
Causes
- Chronic irritation
- inflammation
-
Physiologic
- e.g. monocytes trans. into macrophage
-
Pathologic
- Extrinsic toxin or stressor, generally irreversible
- Exposure to cigerette smoke
-
Dysplasia
- Abnormal differentiation of dividing cells
- abnormal in size, shape and appearance
- Potentially reversible
- may be a precursor of cancer
-
Injury
-
Hypoxic injury
-
Result from
- ↓oxygen in the air
- ↓hemoglobin
- ↓production of RBC
- diseases of the resp. and CV systems
- poisoning of the oxidative enzymes
-
ischemia
- arteriosclerosis
- thrombosis, embolus (cause anoxia)
-
mechanisms
- ↓mitochondrial phophorylation
- ↓ATP production
- ↑ anaerobic metabolism - ↑ ATP from glycogen
- ↓Glycogen ↓anaerobic metabolism
- ↓ATP- failure of Na- K pump
- Sodium- calcium exchange fail
- Intracellular accumulation of sodium and calcium
- Diffusion of potassium out of the cell
- Sodium and water enter the cell freely
- Cellular swelling
- Cells bathe in the fluid rich in the calcium ions
- Cell membrane damage- rapid movement of calcium intracellularly
- Early dilation of the endoplasmic reticulum
- Ribosomes detach and reduce protein synthesis
-
Cellular response
- Reversible if oxygen is restored
- If not, vacuolation within the cytoplasm, swelling of the lysosomes,
mitochondrial swollen and membrane damage
- Accumulation of calcium- activates multiple enzyme systems
- Resulting in cytoskeleton disruption, membrane damage,
activation of inflammation, DNA degradation and eventual cell death
- Irreversible damage
-
Reperfusion
- Xanthine dehydrogenase→ xanthine oxidase
-
superoxide and hydrogen peroxide
- membrane damage and mitochondria calcium overload
-
Free radical injury
-
sources
-
Byproduct of many normal cellular reactions
- Energy generation
- Breakdown of lipids and proteins
- killing microbes by phagocytic white blood cell
-
Molecular oxygen (O2)
- In mitochondria,+4e- toproduce duce water
- partially reduced intermediate species
- O2-, H2O2, OH.
- Transition metals
- Nitric oxide NO
-
Initiated by
- Absorption of extreme energy sources
- Endogenous
- Enzymatics metabolic of exogenous chemical or drugs
-
Reactions
- Lipid peroxidation x1
- Alterations of protein x2
- Alteration of DNA x6
-
major antooxidant enzymes
- SOD
- Catalase
- Glutathione peroxidase
- Antioxidants
-
Impaired calcium homeostasis
- Calcium/magnesium- ATPase exchange systems keep low intracellular calcium level
- Increase influx of Ca++ across the membrane and release from mitochrondria and E.R. when ischemia and presence of toxin
- Activates enzymes to damage cell membrane and cytoskeleton
-
cellular injury
-
Intentional and unintentional injuries
- Contusion
- Hematoma
-
Blunt force injury
- Abrasion
- Laceration
- Fractures
- Sharp force injuries
-
Gunshot wounds
- Entrance wounds
- Exit wounds
-
Asphyxial injury- deprivation of oxygen
- Suffocation
- Strangulation
- Chemical asphyxiants
- Drowning
-
Injury from physical agents
-
Temperature extremes
- Hypothermic injury
- Hyperthermic injury
-
Changes in atmospheric pressure
- Blast injury
- Decompression sickness or caisson disease
-
Ionizing radiation
- X-rays, gamma rays, alpha and beta particles
-
Illumination
- Flourescent lamps
- Eyestrain, obscured vision, and cataract formation
- Caused by light modulation
-
Mechanical stresses
- Physical impact or irritation
-
Noise
- Acoustic trauma and noise-induced hearing loss
-
Chemical injury
- Lead
- Carbon monoxide
-
Ethanol
- Acute alcoholism
- Acetaldehyde
- Fetal alcohol syndrome
- Mercury
- Social or street drugs-
-
Injury from biologic agents
- Pathogenicity of a microorganism
- Virulence of a microorganism
-
Disease-producing potential
- Invasion and destruction
- Toxin production
- Production of hypersensitivity reactions
- Immunologic and Inflammatory Injury
- Injurious Genetic Factors
-
Injury from nutritional imbalances
- Essential nutrients are required for cells to function normally
- Deficient intake
- Excessive intake
- Neoplasia
- Aging
-
death
-
Necrosis
- Sum of cellular changes after local cell death and the process of cellular autodigestion
-
Processes
- Clumping of the nucleus
- Karyolysis
- Karyorrhexis
-
Coagulative necrosis
- Kidneys, heart, and adrenal glands
- Due to hypoxia
-
Protein denaturation
- Gelatine transparent → firm, opaque
- Abnormality in intracellular level of Ca++
-
Liquefactive necrosis
- Neurons and glial cells of the brain
- Soft, liquefies
- Causes: ischemic or bacterial
-
Caseous necrosis
- Tuberculous pulmonary infection
- coagulative+liquefactive necrosis
-
Fat necrosis
- Action of lipases
- Opaque and chalk white
-
Gangrenous
- arteriosclerosis/ blockage of major arteries, esp. in lower leg
-
Somatic Death
- Death of an entire person
- Postmortem changes