Lecture 2 - Response To Cellular Stress Flashcards
What are labile cells?
Labile cells are cells that multiply constantly throughout life (e.g. epithelial cells)
What are stable cells?
Stable cells are cells that multiply only when needed (myocardial cells, liver, the proximal tubules of the kidney and endocrine glands
- Moves through cell cycle
What are quiescent cells?
Quiescent cell are cells in a reversible state which do not divide but retains the ability to re- enter cell proliferation (e.g satellite cells in muscle)
- Leaves cell cycle (G0)
What are causes of cellular stress? (7)
• Oxygen deprivation
• Physical trauma
• Chemical trauma
• Infectious agents
• Immunological agents
• Genetic derangements
• Nutritional imbalances
What is the most common cause of cell injury?
Hypoxia
What are causes of hypoxia?
Inadequate oxygenation
Loss of O2 carrying capacity
• Decreased Haemoglobin
• Decreased RBC production
What is ischaemia?
Restriction of blood supply - most devastating cause of hypoxia
What is the most common cause of general injury to the body?
Ischaemia
What happens during ischaemia?
Waste products cannot be removed. An accumulation of waste products results in pain.
What is hypoxic hypoxia?
Hypoxia insufficient O2 available to lungs which means the lungs are not able to deliver enough O2 to the blood passing through them
What are potential causes of hypoxic hypoxia?
– Drowning
– Blocked airway
– Reduced 02 in atmosphere e.g. high altitude
– Secondary to lung damage
What is anaemic hypoxia?
Hypoxia due to decreased concentration of functional haemoglobin or decreased number of RBCs
What can be the cause of decreased concentration
of functional haemoglobin?
Sickle cell anaemia
Thalassemia
What can be the cause of decreased number of RBCs?
Decreased or delayed production
Increased or early degeneration
What is ischaemic hypoxia?
Hypoxia due to an inadequate blood supply to the tissues
What are types of Ischaemic Hypoxia?
Generalised
Localised
Gradual
Acute
What is an example of generalised ischaemic hypoxia?
Heart Failure
What is an example of localised ischaemic hypoxia?
Vessel obstruction
What is an example of gradual ischaemic hypoxia?
Arteriosclerosis
What is an example of acute ischaemic hypoxia?
Embolus: infarction
What are the different types of physical trauma?
Mechanical
Thermal
• Hypothermia
• Hyperthermia
Electrical
Radiation
Damages DNA
Changes in atmospheric pressure
• Blast injury
• Decompression sickness
What are the different types of chemical trauma?
Hypertonicity
Poisons
Strong acids and alkalis
Environmental pollutants
Recreational drugs.
What are the effects of MDMA in cellular death?
Increase in serotonin which are involved in temperature
regulation.
Increased temperature
Increased water consumption
Cells swell -> burst and die
– Liver cells
– Lung cells
– Brain cells
• Respiration rate declines
• Heart rate increases
• Blood pressure decreases
What are the different types of infectious agents? (5)
• Fungi
• Viruses
• Parasites
• Protozoa
• Bacteria
Where can Helicobacter pylori be found?
In the upper GI tract
What is Helicobacter pylori linked to and why?
Gastric ulcers as it neutralises acid environment of stomach and damages epithelial cells
What is anaphylactic reaction?
Allergic response to allergen
– Drugs
– Insect bites/stings
– foods
What are the two types of genetic derangments?
Mutations - affect protein synthesis
Mendelian single gene disorders
What are the different types of mutations?
Point mutations
Deletions and insertions
Trinucleotide repeat mutations
What is an example of a point mutation?
Sickle cell anaemia
• (CTG->CUG) Glutamic acid to valine
What are the different types of mendelian single gene disorders?
Autosomal dominant
Autosomal recessive
X-linked
What is an example of an autosomal dominant mendelian single gene disorder?
Huntington
What is an example of an autosomal recessive mendelian single gene disorder?
Cystic fibrosis
What is an example of an X-linked mendelian single gene disorder?
Duchenne’s muscular dystrophy
What is Thalassemia?
Inherited mutations that decrease the rate of synthesis of α or β-globin chains leading to haemoglobin deficiency.
What is α-thalassemia usually due to?
α-thalassemia usually due to a deletion of part of the α-globin gene
What is the cause of Huntington disease?
Autosomal dominant
– Manifested in heterozygote
– Repeat expansion of CAG in HD gene to > 35 copies
– Gain of function of HD gene
– Increased number of repeats leads to earlier age of onset
What happens during Huntington’s disease?
Loss of medium spiny striatal neurons that normal dampen motor activity (basal ganglia)
What are the different types of cellular adaption?
• Hypertrophy
• Hyperplasia
• Metaplasia
• Atrophy
What is hypertrophy?
Increase in the SIZE of individual cells and ultimately the entire organ
What is hypertrophy associated with?
Increased accumulation of protein
Increased workload
What is hyperplasia?
Increase in the number of cells caused by an increased rate of cellular division
What is metaplasia?
Reversible replacement of one mature cell type by another, less differentiated cell
What happens cellularly during Barrett’s oesophagus?
Squamous cells become metaplastic and turn into columnar cells in response to this stress.
What happens during Barrett’s oesophagus?
Ongoing reflux of acid from stomach into the oesophagus causes long term stress on these epithelial cells, causing metaplasia
What is atrophy?
Reduction in cell size due to decreased protein synthesis and increased protein degradation due to either normal physiologic or pathologic conditions.
- may result in organ shrinkage
What are the cell changes that occur during atrophy?
Cell changes:
– Reduced endoplasmic reticulum
– Reduced mitochondria
– Reduced myofilaments
What are the causes of atrophy?
• Decreased workload
• Decreased use
• Decreased blood supply
• Decreased nutrition
• Decreased hormonal stimulation
• Aging
• Decreased nervous stimulation
– E.g. poliomyelitis
What is Poliomyelitis (Polio)?
Polio is caused by the Polio virus which damages the anterior horn of motor neurons. This leads atrophy of the limbs due to loss of nerve innervation.
What is reversible adaptation to stress characterised by at the LM level?
At the LM level, reversible adaption is characterised by cellular swelling and fatty change (lipid vacuoles in cytoplasm)
What causes cellular swelling in reversable adaption to stress?
Failure of ATP dependent ion pumps in plasma
membrane
Where does fatty change during reversible adaption to stress occur?
Occurs in cells involved in or dependent on fat metabolism for energy
What is reversible adaptation to stress characterised by at the EM level?
– Swelling of RER
– Detachment of ribosomes
– Swelling of mitochondria
– Plasma Membrane blebs
– Chromatin condensation (nucleus)
