lOMoARcPSD|2764273
Pathology - Summary
Human Physiology and Pathology (Rijksuniversiteit Groningen)
StudeerSnel wordt niet gesponsord of ondersteund door een hogeschool of universiteit
Gedownload door Jesse Fakkert ()
, lOMoARcPSD|2764273
Lecture 1 – Beljaars
Pathology
Etiology → causes of disease.
Pathogenesis → mechanisms of disease,
results in molecular, functional and
morphologic abnormalities in cells and tissues.
Etiology
Various injurious stimuli:
1. Toxins 5. Nutritional imbalances
2. Infectious agents 6. Immunologic reactions
3. Genetic abnormalities 7. Hypoxia and ischemia
4. Physical agents 8. Aging → more inflammation
There are a few ways in which cells respond to damage: adaption, death, inflammation, fibrosis and
neoplastic changes. The way a cell responds depends on the stimulus and the severity of the
stimulus.
Nutritional imbalances
• Lack of nutrition → shortage/insufficiency • Overnutrition → excess → obesity
o Protein-calorie insufficiencies
o Vitamin deficiencies
Hypoxia & ischemia
• Hypoxia → not enough oxygen due to low O2 concentrations from oxygen deprivation.
• Ischemia → not enough oxygen due to reduced blood supply from oxygen deprivation,
deficiency of essential nutrients and/or build up of toxic metabolites. Results in necrosis.
• Anoxia → no oxygen.
Aging
Results from a combination of multiple, progressive cellular alterations. There is a progressive decline
in life span and functional activity of cells. This is caused by getting more mutations in DNA, less
cellular replication and defective protein homeostasis (loss of normal proteins and accumulation of
misfolded proteins). Progressive shortening of telomeres results in cell cycle arrest.
Cellular senescence → reduced ability of cells to respond to stress.
Cellular adaptation
• Adaptation → reversible changes in number, size, phenotype, metabolic activity or function
of cells.
• Physiological adaptions → normal stimulation by hormones or endogenous chemical
mediators.
• Pathological adaptions → responses to stress that allow cell to modulate their structure and
function and thus escape their injury, but at the expense of normal function.
Gedownload door Jesse Fakkert ()
, lOMoARcPSD|2764273
Various forms of cellular adaption:
• Hypertrophy
o Increased cell and organ size, but no new cells. Occurs in
tissues incapable of cell division.
o Can be physiological and pathological.
o Increased functional demand or due to growth factor/hormone stimulation.
o Is reversible, but if the stress is too much or not relieved and the organ can’t
enlarge further → progression toward more degenerative organ changes.
• Hyperplasia
o Increased cell numbers (proliferation) with cells that are capable
of replication and stimulated by growth factors or hormones. (C)
o Reversible, but if it persists it’s a fertile soil for cancer.
o Can be physiological and pathological.
o Hyperplasia and hypertrophy can occur together resulting in an
enlarged organ. (D)
• Atrophy
o Decrease in cell size resulting in an decrease in organ size as a
result of decreased nutrient supply or disuse. Associated with
decreased protein synthesis and increased protein degradation.
o Can be physiological and pathological, reversible
o Reduced cell function, but not cell death.
o Degradation can occur in two cellular compartments:
1. Lysosomes → autophagy
2. Proteasomes → ubiquitin pathway, the breaking down
of cellular proteins. The proteins are labelled with
ubiquitin. The complex is recognized by a proteasome and the
proteasome destroys it through enzymatic activity.
• Metaplasia
o Change in phenotype of differentiated cells that makes cells better able to
withstand adverse environment. Often in response to chronic irritation.
Reversible.
o In epithelial or mesenchymal cells.
Results in reduced functions or increased
propensity for malignant transformation.
Normal cells →
Hyperplasia →
Metaplasia →
Dysplasia →
Neoplasia
Reversible vs irreversible cell injury
Reversible injury: intracellular accumulations, morphological characteristics. 2 main
reasons:
1. Cellular swelling → due to uptake of water, failure of energy dependent ion
pumps in plasma membrane.
2. Fatty change → principally in organs involved in lipid metabolism (liver)
Gedownload door Jesse Fakkert ()
, lOMoARcPSD|2764273
Other reasons:
• Plasma membrane alterations • Nuclear alterations (clumping of
(blebbing) chromatin)
• Swelling mitochondria • Formation of ‘myelin figures’
• Dilation ER and detachment of (damaged membranes)
ribosomes
Pink is cytoplasm, white sections are fat (first H&E staining).
Reversible to irreversible damage
Point of no return: too low amount of [ATP]
• Inability to restore mitochondrial function (oxidative phosphorylation and
ATP generation).
• Loss of structure and functions of the plasma membrane and intracellular membranes.
• Loss of DNA and chromatin structural integrity.
Irreversible injury leading to cell death: depending on the nature and severity of the insult →
necrosis or apoptosis.
Necrosis or apoptosis
Necrosis:
• Major path of cell death, encountered in many injuries. Often associated with
inflammation.
• Form of cell death in which cellular membranes fall apart and cellular enzymes
leak out and digest the cell.
o Inflammatory reaction, leakage of cellular enzymes, the enzymes are elevated in the
blood. This is used as diagnostics, the enzymes can be measured in the blood.
• Fate of necrotic cells
o Phagocytosis by other cells
o Further degradation into fatty acids and these fatty acids can bind calcium salts →
calcification
• Characteristics:
o Cytoplasmic changes
▪ Eosinophilia → denatured proteins and loss of lighter stained glycogen
particles, vacuolated
o Nuclear changes
▪ Pyknosis → nucleus gets more condensed, more pink, reduced DNA
transcription, denatured proteins, loss of lighter stained glycogen particles
▪ Karyorrhexis → degradation of the nucleus, DNAses
▪ Karyolysis → digestion of organelles = ‘moth-eaten’, dissolution of nucleus,
reduced DNA transcription
• Types of necrosis, specific patterns of necrosis are obtained under different
conditions:
o Coagulative necrosis → characteristic for infarcts in all solid organs (not
brain).
o Liquefactive necrosis → characteristic for focal bacterial and some fungal
infections. Hypoxic cell death in brain. The tissue is transformed in a
viscous liquid or pus.
Gedownload door Jesse Fakkert ()
Pathology - Summary
Human Physiology and Pathology (Rijksuniversiteit Groningen)
StudeerSnel wordt niet gesponsord of ondersteund door een hogeschool of universiteit
Gedownload door Jesse Fakkert ()
, lOMoARcPSD|2764273
Lecture 1 – Beljaars
Pathology
Etiology → causes of disease.
Pathogenesis → mechanisms of disease,
results in molecular, functional and
morphologic abnormalities in cells and tissues.
Etiology
Various injurious stimuli:
1. Toxins 5. Nutritional imbalances
2. Infectious agents 6. Immunologic reactions
3. Genetic abnormalities 7. Hypoxia and ischemia
4. Physical agents 8. Aging → more inflammation
There are a few ways in which cells respond to damage: adaption, death, inflammation, fibrosis and
neoplastic changes. The way a cell responds depends on the stimulus and the severity of the
stimulus.
Nutritional imbalances
• Lack of nutrition → shortage/insufficiency • Overnutrition → excess → obesity
o Protein-calorie insufficiencies
o Vitamin deficiencies
Hypoxia & ischemia
• Hypoxia → not enough oxygen due to low O2 concentrations from oxygen deprivation.
• Ischemia → not enough oxygen due to reduced blood supply from oxygen deprivation,
deficiency of essential nutrients and/or build up of toxic metabolites. Results in necrosis.
• Anoxia → no oxygen.
Aging
Results from a combination of multiple, progressive cellular alterations. There is a progressive decline
in life span and functional activity of cells. This is caused by getting more mutations in DNA, less
cellular replication and defective protein homeostasis (loss of normal proteins and accumulation of
misfolded proteins). Progressive shortening of telomeres results in cell cycle arrest.
Cellular senescence → reduced ability of cells to respond to stress.
Cellular adaptation
• Adaptation → reversible changes in number, size, phenotype, metabolic activity or function
of cells.
• Physiological adaptions → normal stimulation by hormones or endogenous chemical
mediators.
• Pathological adaptions → responses to stress that allow cell to modulate their structure and
function and thus escape their injury, but at the expense of normal function.
Gedownload door Jesse Fakkert ()
, lOMoARcPSD|2764273
Various forms of cellular adaption:
• Hypertrophy
o Increased cell and organ size, but no new cells. Occurs in
tissues incapable of cell division.
o Can be physiological and pathological.
o Increased functional demand or due to growth factor/hormone stimulation.
o Is reversible, but if the stress is too much or not relieved and the organ can’t
enlarge further → progression toward more degenerative organ changes.
• Hyperplasia
o Increased cell numbers (proliferation) with cells that are capable
of replication and stimulated by growth factors or hormones. (C)
o Reversible, but if it persists it’s a fertile soil for cancer.
o Can be physiological and pathological.
o Hyperplasia and hypertrophy can occur together resulting in an
enlarged organ. (D)
• Atrophy
o Decrease in cell size resulting in an decrease in organ size as a
result of decreased nutrient supply or disuse. Associated with
decreased protein synthesis and increased protein degradation.
o Can be physiological and pathological, reversible
o Reduced cell function, but not cell death.
o Degradation can occur in two cellular compartments:
1. Lysosomes → autophagy
2. Proteasomes → ubiquitin pathway, the breaking down
of cellular proteins. The proteins are labelled with
ubiquitin. The complex is recognized by a proteasome and the
proteasome destroys it through enzymatic activity.
• Metaplasia
o Change in phenotype of differentiated cells that makes cells better able to
withstand adverse environment. Often in response to chronic irritation.
Reversible.
o In epithelial or mesenchymal cells.
Results in reduced functions or increased
propensity for malignant transformation.
Normal cells →
Hyperplasia →
Metaplasia →
Dysplasia →
Neoplasia
Reversible vs irreversible cell injury
Reversible injury: intracellular accumulations, morphological characteristics. 2 main
reasons:
1. Cellular swelling → due to uptake of water, failure of energy dependent ion
pumps in plasma membrane.
2. Fatty change → principally in organs involved in lipid metabolism (liver)
Gedownload door Jesse Fakkert ()
, lOMoARcPSD|2764273
Other reasons:
• Plasma membrane alterations • Nuclear alterations (clumping of
(blebbing) chromatin)
• Swelling mitochondria • Formation of ‘myelin figures’
• Dilation ER and detachment of (damaged membranes)
ribosomes
Pink is cytoplasm, white sections are fat (first H&E staining).
Reversible to irreversible damage
Point of no return: too low amount of [ATP]
• Inability to restore mitochondrial function (oxidative phosphorylation and
ATP generation).
• Loss of structure and functions of the plasma membrane and intracellular membranes.
• Loss of DNA and chromatin structural integrity.
Irreversible injury leading to cell death: depending on the nature and severity of the insult →
necrosis or apoptosis.
Necrosis or apoptosis
Necrosis:
• Major path of cell death, encountered in many injuries. Often associated with
inflammation.
• Form of cell death in which cellular membranes fall apart and cellular enzymes
leak out and digest the cell.
o Inflammatory reaction, leakage of cellular enzymes, the enzymes are elevated in the
blood. This is used as diagnostics, the enzymes can be measured in the blood.
• Fate of necrotic cells
o Phagocytosis by other cells
o Further degradation into fatty acids and these fatty acids can bind calcium salts →
calcification
• Characteristics:
o Cytoplasmic changes
▪ Eosinophilia → denatured proteins and loss of lighter stained glycogen
particles, vacuolated
o Nuclear changes
▪ Pyknosis → nucleus gets more condensed, more pink, reduced DNA
transcription, denatured proteins, loss of lighter stained glycogen particles
▪ Karyorrhexis → degradation of the nucleus, DNAses
▪ Karyolysis → digestion of organelles = ‘moth-eaten’, dissolution of nucleus,
reduced DNA transcription
• Types of necrosis, specific patterns of necrosis are obtained under different
conditions:
o Coagulative necrosis → characteristic for infarcts in all solid organs (not
brain).
o Liquefactive necrosis → characteristic for focal bacterial and some fungal
infections. Hypoxic cell death in brain. The tissue is transformed in a
viscous liquid or pus.
Gedownload door Jesse Fakkert ()
