Pathology
Adaptation and cell death
03-03-2020
Pathos = suffering, -logos = study of
Etiology (causes of disease) > pathogenesis (mechanisms of disease) > molecular, functional and
morphologic abnormalities in cells and tissues > clinical manifestations (signs and symptoms of
disease)
Microscopic > light microscopy:
- Dyes (histochemistry): HE (hematoxylin-eosin) staining > H: basophilic structures, E:
eosinophilic structures > nuclei blue/purple, cytoplasm pink. But also Masson’s trichrome,
PAS and Sirius red.
- Antibodies (immunohistochemistry): localisation of specific structures (antigens) in biological
tissues with antibodies > binding of antibody to antigen > reaction > strains.
- Substrates (enzyme histochemistry)
Pharmacist:
- Understanding terminology MD
- Understanding therapeutic activities of drugs and its implications
- Co-determine choice of medication
Pathology:
- Terminology
- Characteristics of diseases and its progression
- Understanding drug activities
Etiology: causes of disease
- Various injurious stimuli (e.g. toxins, nutritional imbalances or aging)
- Limited number of cellular responses
Oxygen deficit
- Most common cause of cell injury
- Hypoxia = not enough oxygen due to low O2 concentrations in the blood > oxygen
deprivation. E.g. due to CO poisoning, anaemia, respiratory problems or altitude sickness.
- Ischemia = not enough oxygen due to reduced blood supply > oxygen deprivation +
deficiency of essential nutrients + build up of toxic metabolites. E.g. occlusion of artery.
- Anoxia = no oxygen at all.
Aging:
- Results from combination of multiple, progressive cellular alterations
- Inflammaging
- Progressive decline in life span and functional activity of cells
- Due to: environmental/metabolic insults, telomere shortening and abnormal protein
homeostasis, but also stress and chronic diseases > accumulation of mutations in DNA,
decreased cellular replication and decreased proteins > decreased cell functions or cell loss.
- Diminished ability of cells to respond to stress = cellular senescence
Cellular adaptation: depending on the damaging stimulus different disease outcomes are possible.
- Reversible processes!
- Changes in number, size, phenotype, metabolic activity or function of cells
, - Physiological adaptations: normal stimulations by hormones or endogenous chemical
mediators
- Pathological adaptations: responses to stress that allow cells to modulate their structure and
functions and thus escape injury, but at the expense of normal functions.
Forms of adaptation:
1. Hypertrophy = increase in cell size > increased organ size
- Occurs in cells with a limited dividing capacity (e.g. heart and muscle cells)
- Reversible process, but if stress is too much or not relieved > organ cannot enlarge further >
progression towards more degenerative organ changes
- E.g. phy: muscle growth
- E.g. path: cardiac enlargement from hypertension
2. Hyperplasia = increase in number of cells = proliferation
- Cells capable of replication
- Stimulated by growth factors or hormones
- Reversible, but if it persist it is a fertile soil for cancer
- Hyperplasia and hypertrophy can occur together > uterus enlargement
- E.g. phy: proliferation of the female breast / residual tissue growth
3. Atrophy = decrease in cell size
- Diminished cell function but not cell death
- Associated with decreased protein synthesis and increased protein/organelle degradation >
lysosomes and proteasomes (intracellular proteins) > autophagy / ubiquitin pathway
- Atrophy often associate with autophagy > adaptation to nutrient deprivation > self-eating in
order to provide energy and nutrients > organelles auto phage and fuse with a lysosome >
digested > used as source of nutrients (stress too severe > apoptosis)
- Common causes include: less work load, diminished blood supply, aging
- E.g. phy: decreased work load
- E.g. path: aging and reduced blood supply > brain atrophy
4. Metaplasia = change in phenotype of differentiated cells
- Reversible
- Chronic irritation
- Better able to withstand the adverse environment
- Epithelial or mesenchymal cells
- E.g. change in lung epithelium due to smoking
- Reduced functions or increased chance for bad transformation
Hyperplasia > metaplasia > dysplasia neoplasia (increase in the variation in cell and nuclear sizes +
disordered cellular arrangements)
Reversible injury:
- Cellular swelling: due to over uptake of water > failure of energy dependent ion pumps in
plasma membrane
- Fatty change: principally in organs involved in lipid metabolism (fatty liver!)
- Plasma membrane alterations, swelling mitochondria, dilation ER and detachment of
ribosomes, nuclear alterations, myelin figure formation.
Pathology
Immunology part I
04-03-2020
Immune system:
, - Defence against invaders, such as bacteria/viruses/parasites/fungi
- Removal of dead cells, tumors, artificial objects, damaged molecules
Experience immunology (1600-1900) > experimental immunology (1900-1950) > modern
immunology (1950-now)
Scarlet fever: streptococcus
- No vaccine
- Antibiotics
- Complication when spreads
- Induces autoimmune response (rheumatic fever)
- Rash is caused by pyrogenic exotoxin
Diphtheria: Corynebacterium diphtheriae
- 5-10% fatal
- Diphtheria toxin kills body cells > taken up via endocytosis > acidification of endosome >
release unit A > inhibition protein synthesis > cell dies
Cholera: vibrio cholera
- Diarrhea and vomiting
- Blue death: bluish grey skin due to dehydration
- Intestine bacterium produces cholera toxin > efflux of water and ions into intestinal lumen
Measles: measles morbillivirus
- Highly contagious
- Pneumonia and diarrhoea
Pertussis: whooping cough
- Bordetella pertussis
- Vaccine
Smallpox:
- Virus infection: variola (minor, major)
- Fever, vomiting, sores
- Vaccine first vaccine ever > variolation > lady Montague
Immune system:
- Innate immunity = immunity you are born with (myeloid cells, only takes hours)
- Adaptive immunity = immunity you have to develop (lymphoid cells, takes days)
Severity of epidemic also depend on infectiousness
R0 = Rnaught = virus reproduction number = number of people an individual infects
Higher fatality rate > lower R0, since infected people barely infect others.
R0 depends on virulence of virus, population and vaccination:
- Virulence = how much does the pathogen affects the host > infected people infect others?
- Herd immunity (paraplu effect) because of vaccination/immunization
A new invader! What happens?
- Epithelial barriers: block income as good as possible
- Cellular alarm system
- Tissue-resident immune cells > immediate response and signalling
- Bone marrow: helps signalling cells > specialised help from lymphocytes
, Lymphocytes:
- Tellers: t-helper cells
- Killers: cytotoxic t-cells
- B-cells: produce antibodies
All leukocytes (white blood cells) develop from stem cells in bone marrow or in the yolk sac/fetal
liver. The stem cell develops into a progenitor cell that can differentiate into many types of cells.
White blood cells:
- Monocyte: heart form
- Lymphocytes: round nucleus, less cytoplasm, smaller
- Eosinophil: headphone nucleus
- Basophil
- Neutrophil: 3 ball nucleus
T-cells develop/mature in the thymus, but are generated in the bone marrow.
B-cells develop in the bone marrow.
Nk-cells develop from lymphocytes.
T-/NK-/B-cells are lymphoid cells, the rest are myeloid cells.
Macrophages = eating / clean up of parts.
The mass of all immune cells in the body = mass of brain.
Lymphoid tissue:
- Primary: thymus gland, bone marrow development and maturation
- Secondary: spleen + lymph nodes meeting place for immune cells and antigen
Immune cells in the lymph node sense and intercept pathogens preventing their spread throughout
the body by initiating an immune response.
Spleen: highly vascularized > monitors and filters the blood for ‘rubbish’.
T cells can react to antigens presented by dendritic cells, B cells can react directly themselves.
Lymph nodes get bigger during antibody producement. BALT/GALT/MALT.
Pathology
Adaptation and cell death
03-03-2020
Pathos = suffering, -logos = study of
Etiology (causes of disease) > pathogenesis (mechanisms of disease) > molecular, functional and
morphologic abnormalities in cells and tissues > clinical manifestations (signs and symptoms of
disease)
Microscopic > light microscopy:
- Dyes (histochemistry): HE (hematoxylin-eosin) staining > H: basophilic structures, E:
eosinophilic structures > nuclei blue/purple, cytoplasm pink. But also Masson’s trichrome,
PAS and Sirius red.
- Antibodies (immunohistochemistry): localisation of specific structures (antigens) in biological
tissues with antibodies > binding of antibody to antigen > reaction > strains.
- Substrates (enzyme histochemistry)
Pharmacist:
- Understanding terminology MD
- Understanding therapeutic activities of drugs and its implications
- Co-determine choice of medication
Pathology:
- Terminology
- Characteristics of diseases and its progression
- Understanding drug activities
Etiology: causes of disease
- Various injurious stimuli (e.g. toxins, nutritional imbalances or aging)
- Limited number of cellular responses
Oxygen deficit
- Most common cause of cell injury
- Hypoxia = not enough oxygen due to low O2 concentrations in the blood > oxygen
deprivation. E.g. due to CO poisoning, anaemia, respiratory problems or altitude sickness.
- Ischemia = not enough oxygen due to reduced blood supply > oxygen deprivation +
deficiency of essential nutrients + build up of toxic metabolites. E.g. occlusion of artery.
- Anoxia = no oxygen at all.
Aging:
- Results from combination of multiple, progressive cellular alterations
- Inflammaging
- Progressive decline in life span and functional activity of cells
- Due to: environmental/metabolic insults, telomere shortening and abnormal protein
homeostasis, but also stress and chronic diseases > accumulation of mutations in DNA,
decreased cellular replication and decreased proteins > decreased cell functions or cell loss.
- Diminished ability of cells to respond to stress = cellular senescence
Cellular adaptation: depending on the damaging stimulus different disease outcomes are possible.
- Reversible processes!
- Changes in number, size, phenotype, metabolic activity or function of cells
, - Physiological adaptations: normal stimulations by hormones or endogenous chemical
mediators
- Pathological adaptations: responses to stress that allow cells to modulate their structure and
functions and thus escape injury, but at the expense of normal functions.
Forms of adaptation:
1. Hypertrophy = increase in cell size > increased organ size
- Occurs in cells with a limited dividing capacity (e.g. heart and muscle cells)
- Reversible process, but if stress is too much or not relieved > organ cannot enlarge further >
progression towards more degenerative organ changes
- E.g. phy: muscle growth
- E.g. path: cardiac enlargement from hypertension
2. Hyperplasia = increase in number of cells = proliferation
- Cells capable of replication
- Stimulated by growth factors or hormones
- Reversible, but if it persist it is a fertile soil for cancer
- Hyperplasia and hypertrophy can occur together > uterus enlargement
- E.g. phy: proliferation of the female breast / residual tissue growth
3. Atrophy = decrease in cell size
- Diminished cell function but not cell death
- Associated with decreased protein synthesis and increased protein/organelle degradation >
lysosomes and proteasomes (intracellular proteins) > autophagy / ubiquitin pathway
- Atrophy often associate with autophagy > adaptation to nutrient deprivation > self-eating in
order to provide energy and nutrients > organelles auto phage and fuse with a lysosome >
digested > used as source of nutrients (stress too severe > apoptosis)
- Common causes include: less work load, diminished blood supply, aging
- E.g. phy: decreased work load
- E.g. path: aging and reduced blood supply > brain atrophy
4. Metaplasia = change in phenotype of differentiated cells
- Reversible
- Chronic irritation
- Better able to withstand the adverse environment
- Epithelial or mesenchymal cells
- E.g. change in lung epithelium due to smoking
- Reduced functions or increased chance for bad transformation
Hyperplasia > metaplasia > dysplasia neoplasia (increase in the variation in cell and nuclear sizes +
disordered cellular arrangements)
Reversible injury:
- Cellular swelling: due to over uptake of water > failure of energy dependent ion pumps in
plasma membrane
- Fatty change: principally in organs involved in lipid metabolism (fatty liver!)
- Plasma membrane alterations, swelling mitochondria, dilation ER and detachment of
ribosomes, nuclear alterations, myelin figure formation.
Pathology
Immunology part I
04-03-2020
Immune system:
, - Defence against invaders, such as bacteria/viruses/parasites/fungi
- Removal of dead cells, tumors, artificial objects, damaged molecules
Experience immunology (1600-1900) > experimental immunology (1900-1950) > modern
immunology (1950-now)
Scarlet fever: streptococcus
- No vaccine
- Antibiotics
- Complication when spreads
- Induces autoimmune response (rheumatic fever)
- Rash is caused by pyrogenic exotoxin
Diphtheria: Corynebacterium diphtheriae
- 5-10% fatal
- Diphtheria toxin kills body cells > taken up via endocytosis > acidification of endosome >
release unit A > inhibition protein synthesis > cell dies
Cholera: vibrio cholera
- Diarrhea and vomiting
- Blue death: bluish grey skin due to dehydration
- Intestine bacterium produces cholera toxin > efflux of water and ions into intestinal lumen
Measles: measles morbillivirus
- Highly contagious
- Pneumonia and diarrhoea
Pertussis: whooping cough
- Bordetella pertussis
- Vaccine
Smallpox:
- Virus infection: variola (minor, major)
- Fever, vomiting, sores
- Vaccine first vaccine ever > variolation > lady Montague
Immune system:
- Innate immunity = immunity you are born with (myeloid cells, only takes hours)
- Adaptive immunity = immunity you have to develop (lymphoid cells, takes days)
Severity of epidemic also depend on infectiousness
R0 = Rnaught = virus reproduction number = number of people an individual infects
Higher fatality rate > lower R0, since infected people barely infect others.
R0 depends on virulence of virus, population and vaccination:
- Virulence = how much does the pathogen affects the host > infected people infect others?
- Herd immunity (paraplu effect) because of vaccination/immunization
A new invader! What happens?
- Epithelial barriers: block income as good as possible
- Cellular alarm system
- Tissue-resident immune cells > immediate response and signalling
- Bone marrow: helps signalling cells > specialised help from lymphocytes
, Lymphocytes:
- Tellers: t-helper cells
- Killers: cytotoxic t-cells
- B-cells: produce antibodies
All leukocytes (white blood cells) develop from stem cells in bone marrow or in the yolk sac/fetal
liver. The stem cell develops into a progenitor cell that can differentiate into many types of cells.
White blood cells:
- Monocyte: heart form
- Lymphocytes: round nucleus, less cytoplasm, smaller
- Eosinophil: headphone nucleus
- Basophil
- Neutrophil: 3 ball nucleus
T-cells develop/mature in the thymus, but are generated in the bone marrow.
B-cells develop in the bone marrow.
Nk-cells develop from lymphocytes.
T-/NK-/B-cells are lymphoid cells, the rest are myeloid cells.
Macrophages = eating / clean up of parts.
The mass of all immune cells in the body = mass of brain.
Lymphoid tissue:
- Primary: thymus gland, bone marrow development and maturation
- Secondary: spleen + lymph nodes meeting place for immune cells and antigen
Immune cells in the lymph node sense and intercept pathogens preventing their spread throughout
the body by initiating an immune response.
Spleen: highly vascularized > monitors and filters the blood for ‘rubbish’.
T cells can react to antigens presented by dendritic cells, B cells can react directly themselves.
Lymph nodes get bigger during antibody producement. BALT/GALT/MALT.
Pathology
