Cellular Adaptation to Disease Flashcards
How do cells adapt to disease?
Cells adapt in two ways:
Adjusting their function
- Increase/decrease in mobilisaion of energy, ions
- Increase in enzyme synthesis/function
Modifying their structure
- Increasing/reducing cellular size or number
- Alteration of cell morphology (differentiation)
What are the causes of pathogenesis?
- Genetic* (gene defects, chromosomal defects)
- Nutritional* (deficiency or excess of dietary substance)
- Immune* (damage caused by the immune system)
- Endocrine* (deficient or excessive hormone activity)
- Physical agents* (mechanical trauma, thermal damage, irradiation)
- Chemical agents* (toxicity due to many agents)
- Infection*
- Anoxia* (most commonly due to abnormal respiratory or circulatory function)
What is the cell stress response?
Damaged cells produce proteins that offer protection from damage through a series of metabolic changes known as the cell stress response.
Housekeeping genes are turned down, reducing synthesis of normal structural proteins.
The cell stress genes increase in in expression, coding for cell stress protein synthesis (heat shock proteins =HSPs)
What are the intra- and extra- cellular functions of HSPs?
- Intracellular:* protective function, ubiquitin, interact with components of regulated programmed death.
- extracellular:* mediate immune responses by either innate or acquired immune system?
What are adaptations?
Adaptations are reversible functional and structural responses to physiological stresses and some pathological stimuli, during which new but steady altered states are achieved allowing the cell to survive and continue to function.
What happens when the limits of the adaptive response are exceeded?
A sequence of events follow that is termed cell injury. Cell injury is reversible up to a certain point, but if the srtimulus is severe of persistent enough the cell suffers irreversible injury and ultimately cell death.
What is hypertrophy?
Refers to the increase in the size of the cells, resulting in the increase in the size of the organ
Hypertrophy is caused by an increased functional demand or by stimulation of hormones and growth factors.
Give a pathological and physiological example of hypertrophy
Pathological example: Hypertesnsion and faulty valves result in increased workload on teh heart (chronic haemodynamic overload) which results in hypertrophy.
Physiological: increased growth of uterus during pregnancy stimulated by hormones. Muscle hypertrophy due to increased exercise.
What is hyperplasia?
Hyperplasia is an increase in the number of cells in an organ or tissue, usually resulting in an increased mass of the organ or tissue.
Hyperplasia takes place if the cell population is capable of dividing, and thus increasing the number of cells.
What are the two classes of hyperplasia? Give examples of when they occur.
Physiological hyperplasia can be further classified as:
- Hormonal hyperplasia: increases the functional capacity of a tissue
- Compensatory hyperplasia: increases the tissue mass after damage or partial resection
Pathological hyperplasia is caused by an excess of hormones or growth factors acting on target cells
e.g. psoriasis which is an increased number of skin cells leading to flakiness
What is atrophy?
Atrophy is the reduced size of an organ or tissue resulting from a decrease in cell size.
What are the different classifications of atrophy? Give examples.
- Physiological atropy:* aging
- Pathologic atrophy:*
- Decreased workload
- Loss of innervation: nerve damage can cause muscle atrophy
- Diminished blood supply: ischemia
- Inadequate nutrition: prolonged protein-calorie malnutrition is associated with muscle wasting
- Loss of endocrine stimulation
- Pressure: tissue compression can cause atrophy (tumours can cause atrophy or surrounding tissue)
What is metaplasia?
Metaplasia is a reversible change in which one differentiated cell type is replaced by another cell type.
It may represent an adaptive substition of cells that are sensitive to stress by cell types better able to withstand the adverse environment.
For example, in habitual smokers the normal ciliated columnar epithelial cells of the trachea are replaced by stratified squamous epithelium.
The influences that predispose to metaplasia, if persistent, may initiate malifnants transformation in metaplasia epithelium.
What is connective tissue metaplasia?
It is the formation of cartilage, bone or adipose tissue (mesenchymal tissue) in tissues, that normally do not contain these elements.
After intramuscular haemorrhage, myositis ossification somtimes occurs, where bone is formed in muscle.
What are the different types of cell death?
- Necrosis* occurs when the damage to the membrane is severe, and lysosomal ezymes enter the cytoplasm and digest the cell. Necrosis is always pathological.
- Apoptosis* occurs when the cells DNA or protein is damaged beyond repair, so the cell kills itself.
What are the causes of cell injury?
- Hypoxia
- Physical agents: mechanical trauma, extremes of temperature, sudden changes in atmospheric pressure, radiation and electric shock.
- Chemical changes and drugs
- Infectious agents
- Immunologic reactions
- Nutritional imbalances
What are the types of reversible cell injury?
Reservsible cell injury are structural changes in the cell including:
- Hydropic swelling
- Mitochondrial swelling
- Endoplasmic reticulum dilation
- Fatty change
- Nuclear alteration
- Cytoskeleton disruption
- membrane blebs
- Cytoskeleton disruption
What is the process of hydropic swelling?
Hydropic swelling results from impairment of cellular volume regulation, a process which controls ionic concentrations in the cytoplasm. This regulation involves three components:
- Increased membrane permeability
- Damage to sodium potassium pump
- Interference with ATP synthesis
Hydropic swelling is characterised by an enlarged, pale cytoplasm and a normally located nucleus.
What is the process of fatty change?
Steatosis refers to lipid accumulation forming vacuoles within the cytoplasm. It is often seen in the liver because it is the major organ involved in fat metabolism. It can also occur in the heart, muscle and kidney.
The causes of steatosis include: toxins, protein malnutrition chronic hypoxia, diabetes mellitus, obesity, anorexia
What is the process of mitochondria changes?
Mitochondria can be damaged by increases in cytosolic calcium, reactive oxugen species and oxygen deprivation, and hence are sensitive to virtually all types of injurous stimuli.
Mitochondria can undergo various changes:
- *Swelling: *occurs in acute injury, particularly ischemia.
- Rarefaction: decrease in number
- Amorphous densities: phospholipid rich
Endoplasmic reticulum disruption
Dilation
Polysomic disaggregation and detachent
Accumulation of free ribosomes in cytoplasm
Membrane blebs
Caused by the decoupling of the cytoskeleton from the cell mmbrane, causing the cell to bulge.
What is necrosis?
Necrosis is the combination of all morpholic phenomena that occurs in cells or tissues and consequent death.
Coagulative necrosis
Occurs as the result of protein denaturing, causing the albumin and protein to form a firm and opaque state. The architecture of the cell is maintained.
Coagulative necrosis is typically seen in hypoxic environments (such as infarction). Ischemia is the most common cause of necrosis.
It occurs commonly in teh heart, kidneys and adrenal glands but not in the brain.
A localised area of coagulative necrosis is called an infarct.
Histologically, what does coagulative necrosis look like?
Eosinophilic (from the released proteins) and anucleate.
What is liquefactive necrosis?
Dead cells are digested to form a liquid mass, thus losing thr cell architecture. The necrotic liquid mass is frequently creamy yellow due to the presence of dead leukocytes (pus).
Liquefactive necrosis is seen in bacterial infections and sometimes fungal infections because of their ability to stimulate an inflammatory response.
For unknown reason, hypoxic death of cells within the CNS often manifests as liquefactive necrosis.
What is gangrenous necrosis?
Gangrenous necrosis is classified as either dry (coagulative) or wet (liquefactive). It differs from other types of necrosis because it applies to multiple tissue planes (usually a limb).
When a bacterial infection is superimposed it becomes ‘wet gangrene’.
What is caseous necrosis?
It is a combination of coagulative and liquefactive necrosis. It is typically caused by mycobacteria, fungi and some foreign substances. It is encounteres most often in tuberculosis infections.
The area appears white, friable and crumbly.
Histologically, how does caseous necrosis appear?
The necrotic area appears as a collection of fragmented or lysed cells and amorphous granular debris.
What is fatty necrosis?
The specialised necrosis of fat tissue, resulting from the activated lipases acting on fatty tissue such as in the pancreas (acute pancreatitis) and teh peritoneal cavity.
Triglycerides are broken down into fatty acids which react to calcium to form ‘soaps’, surrounded by inflammation.
What is fibroid necrosis?
A special form of necrosis usually seen in immune reactions involving blood vessels. It typically occurs when complexes of antigens and antibodies are deposited in the walls of arteries.
Fibroid necrosis is seen in immunologically mediated vasculitis syndromes.
