Medical-Surgical Pathology Notes
Concepts and Fundamentals of Ageing
● Pathology Concepts
○ Pathology = Study of structural/functional causes of disease
➢ Aetiology - cause
➢ Pathogenesis - mechanism
➢ Morphological change - induced structural alterations
➢ Clinical significance - functional consequences of morph change
○ Homeostasis - physiological balance
➢ Cells respond to excessive physiological stress
● Adaptation - new state with preserved viability
● Reversible Injury - can be restored to normal
● Irreversible Injury - change is permanent
● Cell Death - necrosis or apoptosis
● Cellular Responses
○ Adaptation
➢ Hypertrophy - increase in size (GFs induced)
➢ Hyperplasia - increase in number (hormone/GF induced)
➢ Atrophy - decreased cell size (autophagy/decreased synth)
➢ Metaplasia - change in phenotype
○ Reversible Lesions
➢ Biochemical and Morphological Changes
● To normal, if stress stops
● To cell death, if stress continues
➢ Hydropic Degeneration
● Cell swelling due to water and Na accumulation
➢ Intracellular Accumulation
● Fatty change
● Intermediate metabolite accumulation
● Exogenous substance accumulation
○ Irreversible Lesions and Cell Death
➢ Apoptosis - activated self-destruction
● Physiological or pathological aetiology
● Organised disassembly of cell components
● Minimal disruption of tissue
● Minimal/absent inflammation
● Chromatin condensation and fragmentation
➢ Necrosis - pathological cell death
● Severe swelling and protein coagulation/denature
● Organelle breakdown and cell rupture
● Many cells affected
, ● Inflammatory infiltrate in tissue
● Types
○ Coagulative - most common
■ Cell framework preserved
■ Protein denaturation
■ Hypoxic death (except brain)
○ Liquefactive - soft liquidy area
■ More lysis than protein denaturation
■ Frequent in abscesses and in brain
○ Gangrenous - no specific pattern
■ Coag necrosis in a limb
■ More liquefactive - wet gangrene
○ Caseous - TB lesions
■ Soft, cheesy material
■ Amorphous eosinophilic w/ debris
○ Fat - in adipose tissue
■ Lipase releases fatty acids from TGs
■ Soaps formed combining with Ca
■ White, chalky saponified areas
■ Vague cell outline and Ca deposition
○ Fibrinoid - Ab:Ag deposition in BVs
■ Bright pink amorphous material in BV
■ Associated with inflamm/thrombosis
● Cell Injury
○ Causes
➢ Hypoxia
● Affects ATP generation
● Caused by Ischaemia, anaemia, CO poisoning
➢ Physical Agents
● Trauma, heat/cold, radiation, electric shock
➢ Chemical Agents
● Drugs, poisons, pollutants
➢ Infectious Agents
● Bacteria, viruses, fungi, parasites
➢ Immunological Reactions
● Autoimmune diseases
● Response to infection
➢ Genetic Derangements
● Chromosomal alterations or specific gene mutations
➢ Nutritional Imbalance
● Protein or vitamin deficiency
○ Mechanisms
➢ Responses to cell injury depend on injury/duration/severity
● Consequences depend on type/state/adaptability of cell
, ➢ Injury results from cellular element perturbation
● ATP Production
○ Often from ischemia / toxic injury
● Mitochondrial Damage
○ Hypoxia or toxins
● Plasma Membrane Integrity
○ Ischaemia or toxins
● Oxidative Stress
○ Autocatalytic reactions
● Protein
○ Non-reversible DNA damage → apoptosis
● Genetic Apparatus Integrity
● Ageing
○ Spain
➢ Inverted population pyramid
➢ More over 65s than under 15s
➢ Life expectancy = 81.1 years
○ Chronology of Ageing
➢ Max = 120
➢ Med = 80 in 2000 (35 in 1900)
○ Characteristics
➢ Universal
➢ Intrinsic
➢ Progressive
➢ Heterogeneous
➢ Deleterious
○ General
➢ Gradual process of deterioration of organism’s functional
capacity after maturity which eventually leads to its death
➢ Not disease by itself, but related to chronological diseases
➢ Decreases quality of life by
● Immunosenescence
● Loss of regenerative capacity
● Decreased homeostatic resilience
➢ Affects all species
● Each has different life expectancy
● Modulated by genetic/molecular cell factors
● Lifestyle plays role
○ Theories
➢ Free Radical Theory - Hartman, 1956
● Ageing caused by accumulation of Oxi injuries
● Intracellular metabolic processes, or external factors
➢ Telomere Shortening Theory - Cerbere, 2002
● Telomere shortens with cellular divisions
, ● Chromosomes end up more unstable; likely to mutate
➢ Stem Cells Theory - Ruzankina, 2007
● Cell replacement loss with age, less regen
● Less resilient to stress damage
○ Hayflick Limit
➢ Culture of FBs of diff mammals
● First to stop dividing were less long-lives species
● Half-life can be lengthened, but genetically programmed
○ General Effects
➢ Body Composition
● Decrease in muscle/bone
● Increase in fat
➢ Organ Structure
● Decrease in cell population
● Decrease in collagen / elastin
➢ Functional Organ Alterations
● Decreased number and function of cells
➢ Decreased Functional Reserves
● Less homeostatic maintenance and repair
➢ Appearance
● Decrease in height
● Kyphosis
● Fat distribution
● Joint flexure
➢ Skin
● Decreased elasticity and thickness
● Increased wrinkling and facial/nose hair
➢ Systems
● Resp/circulatory/digestive/urinary/endocrine/nervous
● Blood
○ Ageing in Oral Cavity
➢ Maxillary Bone Ageing
● Loss of skeletal bone mass
○ Decreased osteoblast
○ Increased osteoclast
○ Decreased bone chemicals (Ca/P/Na/Mg)
○ Decreased organic matrix
● More spongy bone
○ Pneumatisation of max sinuses
○ Increase in intratrabecular space
○ Less jaw mobility
➢ Mandible less affected
➢ TMJ
● Bruxism due to loss of neurological coordination
Concepts and Fundamentals of Ageing
● Pathology Concepts
○ Pathology = Study of structural/functional causes of disease
➢ Aetiology - cause
➢ Pathogenesis - mechanism
➢ Morphological change - induced structural alterations
➢ Clinical significance - functional consequences of morph change
○ Homeostasis - physiological balance
➢ Cells respond to excessive physiological stress
● Adaptation - new state with preserved viability
● Reversible Injury - can be restored to normal
● Irreversible Injury - change is permanent
● Cell Death - necrosis or apoptosis
● Cellular Responses
○ Adaptation
➢ Hypertrophy - increase in size (GFs induced)
➢ Hyperplasia - increase in number (hormone/GF induced)
➢ Atrophy - decreased cell size (autophagy/decreased synth)
➢ Metaplasia - change in phenotype
○ Reversible Lesions
➢ Biochemical and Morphological Changes
● To normal, if stress stops
● To cell death, if stress continues
➢ Hydropic Degeneration
● Cell swelling due to water and Na accumulation
➢ Intracellular Accumulation
● Fatty change
● Intermediate metabolite accumulation
● Exogenous substance accumulation
○ Irreversible Lesions and Cell Death
➢ Apoptosis - activated self-destruction
● Physiological or pathological aetiology
● Organised disassembly of cell components
● Minimal disruption of tissue
● Minimal/absent inflammation
● Chromatin condensation and fragmentation
➢ Necrosis - pathological cell death
● Severe swelling and protein coagulation/denature
● Organelle breakdown and cell rupture
● Many cells affected
, ● Inflammatory infiltrate in tissue
● Types
○ Coagulative - most common
■ Cell framework preserved
■ Protein denaturation
■ Hypoxic death (except brain)
○ Liquefactive - soft liquidy area
■ More lysis than protein denaturation
■ Frequent in abscesses and in brain
○ Gangrenous - no specific pattern
■ Coag necrosis in a limb
■ More liquefactive - wet gangrene
○ Caseous - TB lesions
■ Soft, cheesy material
■ Amorphous eosinophilic w/ debris
○ Fat - in adipose tissue
■ Lipase releases fatty acids from TGs
■ Soaps formed combining with Ca
■ White, chalky saponified areas
■ Vague cell outline and Ca deposition
○ Fibrinoid - Ab:Ag deposition in BVs
■ Bright pink amorphous material in BV
■ Associated with inflamm/thrombosis
● Cell Injury
○ Causes
➢ Hypoxia
● Affects ATP generation
● Caused by Ischaemia, anaemia, CO poisoning
➢ Physical Agents
● Trauma, heat/cold, radiation, electric shock
➢ Chemical Agents
● Drugs, poisons, pollutants
➢ Infectious Agents
● Bacteria, viruses, fungi, parasites
➢ Immunological Reactions
● Autoimmune diseases
● Response to infection
➢ Genetic Derangements
● Chromosomal alterations or specific gene mutations
➢ Nutritional Imbalance
● Protein or vitamin deficiency
○ Mechanisms
➢ Responses to cell injury depend on injury/duration/severity
● Consequences depend on type/state/adaptability of cell
, ➢ Injury results from cellular element perturbation
● ATP Production
○ Often from ischemia / toxic injury
● Mitochondrial Damage
○ Hypoxia or toxins
● Plasma Membrane Integrity
○ Ischaemia or toxins
● Oxidative Stress
○ Autocatalytic reactions
● Protein
○ Non-reversible DNA damage → apoptosis
● Genetic Apparatus Integrity
● Ageing
○ Spain
➢ Inverted population pyramid
➢ More over 65s than under 15s
➢ Life expectancy = 81.1 years
○ Chronology of Ageing
➢ Max = 120
➢ Med = 80 in 2000 (35 in 1900)
○ Characteristics
➢ Universal
➢ Intrinsic
➢ Progressive
➢ Heterogeneous
➢ Deleterious
○ General
➢ Gradual process of deterioration of organism’s functional
capacity after maturity which eventually leads to its death
➢ Not disease by itself, but related to chronological diseases
➢ Decreases quality of life by
● Immunosenescence
● Loss of regenerative capacity
● Decreased homeostatic resilience
➢ Affects all species
● Each has different life expectancy
● Modulated by genetic/molecular cell factors
● Lifestyle plays role
○ Theories
➢ Free Radical Theory - Hartman, 1956
● Ageing caused by accumulation of Oxi injuries
● Intracellular metabolic processes, or external factors
➢ Telomere Shortening Theory - Cerbere, 2002
● Telomere shortens with cellular divisions
, ● Chromosomes end up more unstable; likely to mutate
➢ Stem Cells Theory - Ruzankina, 2007
● Cell replacement loss with age, less regen
● Less resilient to stress damage
○ Hayflick Limit
➢ Culture of FBs of diff mammals
● First to stop dividing were less long-lives species
● Half-life can be lengthened, but genetically programmed
○ General Effects
➢ Body Composition
● Decrease in muscle/bone
● Increase in fat
➢ Organ Structure
● Decrease in cell population
● Decrease in collagen / elastin
➢ Functional Organ Alterations
● Decreased number and function of cells
➢ Decreased Functional Reserves
● Less homeostatic maintenance and repair
➢ Appearance
● Decrease in height
● Kyphosis
● Fat distribution
● Joint flexure
➢ Skin
● Decreased elasticity and thickness
● Increased wrinkling and facial/nose hair
➢ Systems
● Resp/circulatory/digestive/urinary/endocrine/nervous
● Blood
○ Ageing in Oral Cavity
➢ Maxillary Bone Ageing
● Loss of skeletal bone mass
○ Decreased osteoblast
○ Increased osteoclast
○ Decreased bone chemicals (Ca/P/Na/Mg)
○ Decreased organic matrix
● More spongy bone
○ Pneumatisation of max sinuses
○ Increase in intratrabecular space
○ Less jaw mobility
➢ Mandible less affected
➢ TMJ
● Bruxism due to loss of neurological coordination
