Disease and Homeostasis Flashcards
What are the causes of cell injury?
- oxygen deprivation
- chemicals
- enzymes
- infectious agents
- immunological reactions
- genetic defects
- nutritional imbalances
- trauma
How does oxygen deprivation cause cell injury?
oxygen deprivation = hypoxia
tissues therefore do not get adequate oxygen ad begin to die (ischemia)
How do chemicals cause cell injury?
affects osmotic environment either causing or by altering membrane permeability
Immunological reactions which can cause cell injury
- anaphylaxis
- autoimmune disorder
Traumas which can affect cell injury
- extremes of temperature
- radiation
- atmospheric pressure
What are the consequences of ischemia to cells
- No aerobic energy production
- depletion of ATP
- if ATP is low then anaerobic glycolysis and AMP become increased leading to
the accumulation of lactic acid and a drop in intracellular pH (can lead to
protein degradation and function impairment)
- Removal of wastes cannot occur as blood has stopped flowing to the area
What are free radicals
- atoms with a single unpaired electron
- unstable
- very reactive
How are free radicals formed in normal respiration
molecular oxygen has a single unpaired electron
If two come together with the addition of a floating electron a superoxide radical is formed
How are free radicals formed in the body
- radiation exposure
- oxygen toxicity
- ageing
- inflammation
- chemicals (smoking, air pollution)
What damage do free radicals cause
- lipid peroxidation of membranes (double bonds attacked losing structure and function)
- DNA oxidation
- 8-oxoguanine and thymine glycol are common oxidative lesions
- if not fixed by base excision repair will cause mutations when multiplying
- Protein cross linking
- new covalent or ionic bonds added
- can change structure and function
How do you remove free radicals
- electron donation
- antioxidants
REMOVING FREE RADICAL PATHWAYS
What factors facilitate O2 becoming superoxide
- enzymes in the ER
- peroxisomes
REMOVING FREE RADICAL PATHWAYS
What enzyme facilitates superoxide becoming H2O2 (hydrogen peroxide)
superoxide dismutase (SOD)
REMOVING FREE RADICAL PATHWAYS
Once superoxide has become H2O2 what are the two different end products and which are safe for the body
- O2 + H2O
- safe
- OH
- hydroxyl radical (not safe)
REMOVING FREE RADICAL PATHWAYS
What enzymes facilitate hydrogen peroxide becoming O2 and H2O
- glutathione peroxidase
- catalase
REMOVING FREE RADICAL PATHWAYS
Which 2 reactions facilitate H2O2 to hydroxyl radical
Fenton reaction
- Fe3+ and H2O2 = Fe2+ and OH-
Haber-Weiss Reaction
- H2O2 and superoxide = OH-
REMOVING FREE RADICAL PATHWAYS
Why can metals (Fenton reaction) factor in to facilitating this pathway
transition metals can accept or donate electrons ap can catalyse free radical formation
Which antioxidants are important for removing free radicals
- vitamin C
- coenzyme Q10 (ubiquinone)
What are the cellular adaptations to injury/physiological change
- atrophy
- hypertrophy
- hyperplasia
- metaplasia
- dysplasia
what is atrophy
decrease in size or number of cells
examples of atrophy
Muscle atrophy
- decrease in muscle mass due to decrease workload (immobilisation of limb)
atrophy of optic nerve
- decrease in vision due to a loss of hormones (e.g. during menopause)
cerebral atrophy
- decrease of cerebral cortex
- alzheimers, ageing, alcohol
What is the role of lysosomes
- degrade proteins, carbohydrates, lipids and acids
2. storage of. substances which cannot be metabolised completely (creates residual bodies)
Lysosome catabolism can occur in 2 ways. What are these ways
- Heterophagy
- environmental substances endocytosed
- fuses which amphisome
- fuses with lysosome to create and autolysosome which breaks down substance - Autophagy
- cytoplasm or damaged organelles enclosed in autophagosome
- fuses with lysosome to create autolysosome to break down contents
Lysosome Storage disorders
- Hurler Syndrome
- defect in glycosaminoglycan breakdown allowing it to accumulate in cytoplasm - Tay-Sachs disease
- defect in degradation of lipids in nerve cells
Cellular Basis of atrophy
two proteolytic systems (breakdown of proteins)
- lysosomes
- ubiquitin pathway
- digestion in protostomes
what is hypertrophy
increased size of cells
What can cause hypertrophy
- exercise
- hormones (uterus and breast during puberty)
- toxins (can cause liver enlargement)
- hypertension (high blood pressure which causes heart muscle to work harder and therefore thicken)
What is hyperplasia
increase in number of cells
Examples and causes of hyperplasia
example:
- benign prostatic hyperplasia
- gingival hyperplasia
causes:
physiological: hormonal, growth factors
pathological: excessive hormones (endometriosis)
What is metaplasia
reversible conversion of normal cells to less specialised cells due to prolonged exposure to stimulus
can withstand stress better but may not retain same functions
Example of metaplasia
Chronic gastric reflux
- stratified squamous of lower oesophagus becomes intestine like due to chronic gastric acid exposure from reflux
What is dysplasia
disorderly growth
- cells become variable in morphology and disorganised
- may give rise to cancer
Examples of dysplasia
cervical dysplasia
- precursor for squamous cell carcinoma of cervix
can be detected via cervical screening test
Cellular stress causes which 2 types of injury
- reversible injury
2. irreversible injury
What are the consequences of reversible injury to cells
cellular adaptations
- atrophy
- hypertrophy
- hyperplasia
- metaplasia
- dysplasia
What are the consequences of irreversible injury
- cellular senescence
- cancer
- necrosis
- apoptosis/autophagy
What can cause cellular ageing
- cellular senescence
What can cause cellular death
- cancer
- necrosis
- apoptosis/autophagy
- ageing
Lifespan has changed over the years what factors contribute to this?
early 19th century to 1900
- improved housing, sanitation and antiseptics
1900-1935
- improved public health, hygiene and immunisation
1935-1960
- antibiotics, improved medical practices, nutrition, health education
1960-1980
- recent biomedical advancements
What is cell senescence
inbuilt programme to irreversibly arrest cell growth
- prevents damaged cells developing into cancer cells
Happens at a higher frequency with age
Cells show what sort of phenotypic changes in senescence
increased size and presence of intracellular inclusions
different gene expression pattern
different metabolic programme
secrete pro-inflammatory cytokines, chemokines, protein digesting extracellular matrix proteases
- can cause cells around them to undergo damage and possibly enter senescence
How are natural selection and ageing connected
natural selection diminishes with age as it only affects organisms during reproducing stages
If diseases develop post reproduction age = the contributing genes will not be selected against
(if you have already reproduced then these genes will already be passed to the next generation)
Examples:
- cancer
- heart disease
- Alzheimer’s
Which diseases illustrate the effects of genes expressed before and after reproductive years
before reproduction
- Progeria
after reproduction
- Huntingtons disease
What is Progeria
AKA Hutchinson-Gilford Progeria Syndrome
Rare disease as individuals die before reproducing
Autosomal dominant genetic mutation (not inherited mutations)
Progeria symptoms
resemble aspects of ageing manifested at an early age
- wrinkles and slow growth
- boldness
- large head compared to body
- skin ageing
- joint stiffness
- cardiovascular problems
- death at about 12 years from heart attack or stroke
Genetic factors involved in Progeria
Lamin A (LMNA) gene - needed for structural scaffolding of the nuclear envelope at embryonic stage
this gene is mutated causing disrupted nucleus and limits ability of cells to divide
What is Huntington’s Disease
autosomal dominant neurodegenerative disorder
- arises in middle age so natural selection is powerless
Symptoms of Huntington’s Disease
- involuntary contorting movements
- dementia
- slurred speech
- delusions
- immobilised contorted positions
Normal and disease gene contributing to Huntington’s
increased repeated sequence of CAG in huntin protein (HTT) Chromosome 4
normal = 6-34 repeats
HD = 40-55 repeats
early onset HD = 70 + copies
Molecular basis of Huntington’s
- HTT is expressed in all somatic tissues and highly expressed in neurons
- more repeats the more unstable the protein and may cause protein aggregation
- HTT interacts with many other proteins
Molecular effects of mutant HTT proteins
not well known but:
- formation of inclusion bodies in nucleus of cells
- protein aggregation in cytoplasm
leading to:
- synaptic dysfunction
- mitochondrial toxicity
- decrease in rate of axonal transport
Huntington’s effect on the brain
atrophy and cell death of basal ganglia
- degeneration of cells from putamen and caudate nuclei
basal ganglia involved in:
- motor control of movement
- cognition
- sensory pathways
What are common ageing disorders
- Werner disease (adult progeria)
- premature with later onset than progeria (usually teens)
- average lifespan = 46 - Progeria (Hutchinson-guildford)
- premature ageing with early onset
- average lifespan = 12 years
What is werner disease and symptoms
autosomal recessive
symptoms:
- atherosclerosis
- diabetes
- cataracts
- osteoporosis
- cancer
- wrinkles
- greying of hair
What genetic mutation causes Werner’s Disease and how does this effect the protein?
nonsense, frame shift mutation in WRN gene Chromosome 8
- creates a truncated, short protein
WRN is a helicase
- separates strands of DNA for replication
Werner Disease molecular basis
- cells sensitive to DNA cross linking and ionizing radiation
- cells show impaired DNA replication
- reduced replicative lifespan
- defects in telomeres causing genomic instability and cancer
What are the two processes of death at a cellular level
- Necrosis
2. Apoptosis
What is necrosis and the molecular basis
Necrosis is the result of death from cell injury
- death by autolysis
- cells swell and burst and spills its contents
- causes an inflammatory response
- organelles disintegrate and mito dialtes, no change to nucleus
Causes gangrene
What causes necrosis
toxins
hypoxia
inhibition of major biochemical pathways
- glycolysis - oxidative phosphorylation - krebs cycle - all leads to no ATP
What is gangrene and the types of gangrene
lack of blood in an area which causes large area of dead tissue
- often occurs in extremities but sometimes in bowel
types:
- dry
- wet
- gas
- freezing
What is dry gangrene
symptoms:
- black, dry wrinkled tissue
- black due to black iron sulphide from leftover haemoglobin
where:
- only in extremities
why:
- ischemia
What is wet gangrene
where:
- internal organs
why:
- bacteria and toxins which invade the blood
What is gas gangrene
why:
- bubbles of gas from anaerobic bacteria Clostridium
symptoms:
- black blister like sores
What is freezing gangrene
why:
- formation of water crystals which increase pressure of remaining fluid and cells burt
symptoms:
- blister like
