1- Causes of disease: overview Flashcards
What is etiology?
- cause or causes of disease
- first studied by Hippocrates
What are idiopathic diseases?
Conditions with no known cause
What is sporadic?
Diseases that occur at random with no obvious patterns- i.e. at random, irregular intervals
How can causes of disease be classified?
- intrinsic= from within body
- extrinsic= from outside body
Name extrinsic causes of disease
- Injury
- Infection
- Nutrition and diet
- Lifestyle, e.g. smoking, exposure to workplace toxins
- Chemical poisoning (acute and chronic)
- Exposure to radiation
Name intrinsic causes of disease
=Changes in an individual’s genome
- Nuclear or mitochondrial
- Inherited mutations and other genetic variations
- de novo mutations
- Epigenetic modifications- chemical DNA methylation, phosphorylation, acetylation of histones, no change to DNA sequence but behaviour of DNA changed, and expression of genes changed
Intrinsic causes- What do changes to genome lead to?
Typically alter the function of a gene (or group of genes)
E.g. more/less protein or same amount but more/less activity
Intrinsic causes- At what levels can the effects of genetic variations manifest?
-Cell autonomously
Cell X no longer expresses structural protein Y, so cell X is the wrong shape.
-Cell non-autonomously
Cell X no longer secretes protein hormone Y, so cell Z no longer functions.
State the 3 grey areas.
- Terms intrinsic or extrinsic can be ambiguous
- Causes of disease are often a chain of events. eg. Are allergies caused by a sensitive immune system (intrinsic) or the preceding allergen (extrinsic)?
- Intrinsic or extrinsic depends on viewpoint, i.e. extrinsic to what: cell, tissue, organ, body?
Age is a contributing factor to many diseases, but is it a cause?
Age is a synonym ‘time’, in the context of causes that accumulate, e.g. number of mutations accumulating= accumulated cancer risk overtime
When is age an intrinsic cause?
When it describes biological process of ageing
ageing - menopause - decreased oestrogen - risk of osteoporosis
-Many diseases associated with chronic inflammation also have a biological ageing as a cause
What are the alternative descriptions of causes of disease?
Genetic and environmental
These terms are versions of intrinsic and extrinsic that are more reflective of that disease
What diseases have intrinsic causes?
Cancer (inc. Leukaemia, Lymphoma, Myeloma, Breast, Prostate)
Developmental diseases(e.g. Neural tube defects)
Inherited anaemia(e.g. Sickle cell disease, β-thalassaemia)
Inherited metabolic diseases(e.g. phenylketonuria)
What is the cause of Down Syndrome?
- Trisomy of chromosome 21, inherited at conception
- Intrinsic
What is the cause of COVID-19?
Infection with SARS-CoV-2
Extrinsic
What are the causes of lung cancer?
Extrinsic -smoking tobacco -chemicals and workplace risks -air pollution -exposure to radon gas Intrinsic -previous lung disease -family history of lung cancer
What are the phases of cell cycle?
G1phase,
Sphase(synthesis)
G2phase
Mphase(mitosisand cytokinesis)
Describe mitosis?
Prophase: chromosomes condense, centrosomes move to opposite poles, mitotic spindle forms
Prometaphase: breakdown of nuclear envelope, chromosomes attach to mitotic spindle via the kinetochore
metaphase: centrosome are at opposite poles, chromosome are at their most condensed and line up at the equator of the mitotic spindle
anaphase: sister chromatids separate synchronously, each new daughter chromosome moving to the opposite spindle pole
telophase: chromosome arrives at the spindle poles, chromosomes decondense, nuclear envelope reforms
cytokinesis: cytoplasm divides, at the position of the metaphase plane, contractile ring of actin and myosin II constrict the cell into two new cells
What are mitogens?
A mitogen is a peptide or small protein that induces a cell to begin cell division: mitosis.
What factors control the cell cycle?
Positive regulators= cyclins and cyclin-dependent kinases (Cdk)
Cdk bound to cyclin- active- phosphorylate target protein
Cdk activation triggers the next step in the cell cycle such as entry into S phase, M phase
Cyclin degradation terminates Cdk activity
What mechanisms underlie cell death?
Intrinsic- mitochondrial pathway, mediated by noxious stimuli that lead to mitochondrial injury
Extrinsic- death receptor pathway, mediated by activation of death receptors and BCL-2 regulated
