Pathology Flashcards
What is Atherosclerosis?
The process by which plaques made of fibrous tissue, lipids, cholesterol and lymphocytes build up in arteries over time. Can cause the arteries to narrow and harden, restricting the blood flow and oxygen supply.
Progresses over lifetime.
What are the risk factors for Atherosclerosis?
Smoking Hypertension Type 2 diabetes that is poorly controlled Hyperlipidaemia Obesity Physically inactive
What are the theories concerning what causes Atherosclerosis?
Lipid insudation theory: high levels of lipids in the blood infiltrate the walls of the arteries to cause the atherosclerotic plaque to form.
BUT the lipids present in the plaque were different and the theory did not account for the fibrosis and inflammation present.
Instead: caused by endothelial cell damage on the lining of the arteries, caused by nicotine, increased lipid, shearing forces from hypertension at bifurcation points or poorly controlled diabetes.
How does an Atherosclerotic plaque form?
Begin as fatty streaks early in life which can develop overtime to produce a plaque in the artery wall.
Over time, damage to endothelial wall causes addition of platelets and fibrosis tissue. The endothelial layer repairs but more of the lumen is occluded.
Haemorrhage can speed up the process.
As the blockage gets bigger, more of the artery is occluded, causing onset of symptoms e.g. claudication
What is Apoptosis?
A genetically directed process of cell self-destruction that is marked by the fragmentation of nuclear DNA. A normal physiological process eliminating DNA-damaged, superfluous, or unwanted cells. Activated either by the presence of a stimulus or removal of a suppressing agent or stimulus.
In the process of apoptosis, the cell undergoes blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay before being engulfed by a phagocyte.
Bcl2 protein and Fas receptor-ligand complex activate caspases which activate Apoptosis.
When is Apoptosis useful and harmful?
Apoptosis is useful in development - we required many cells to die in order to change webbed fingers into digits.
Tissues with a high-cell turnover require apoptosis to remove cells that have stopped being useful.
Lack of apoptosis leads to cancer (uncontrolled cell growth).
Too much apoptosis leads to HIV.
What is Necrosis?
Unprogrammed and traumatic death of cells due to disease, injury or failure of the blood supply.
Various receptors are activated, and result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space.
What is Necrosis?
Unprogrammed and traumatic death of cells due to disease, injury or failure of the blood supply.
Various receptors are activated, and result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space.
Examples include cerebral infarction and avascular necrosis of bone (particularly scaphoid bone).
What are the different types of Necrosis?
Coagulative necrosis: Architecture of dead tissue is preserved
Liquifactive necrosis: Digestion of dead cells form a viscous liquid mass
Caseous necrosis: Maintains a cheese-like appearance, the dead tissue appears as a soft and white proteinaceous dead cell mass.
What is Hypertrophy?
Increased size of tissue due to increased size of the constituent cells.
e.g. mutation in myostatin gene which would normally provide restriction on muscle cell size
What is Hyperplasia?
Increased size of tissue due to increase in number of constituent cells.
e.g. benign hypostatic hyperplasia in prostate smooth muscle or endometrium tissue
What is Atropy?
Decrease in size of tissue caused by a decrease in constituent cells or a decrease in their size.
e.g. Alzheimer’s or optic atropy
What is Metaplasia?
Change in differentiation of a cell from one fully differentiated cell to another fully differentiated cell.
e.g. cilia usually move mucous up the bronchial tree, but in smoking they are directly affected so ciliated columnar epithelium differentiate into squamous epithelium.
No cilia present means increased incidence of infection/disease.
What is Dysplasia?
Imprecise term for the morphological changes seen in cells in the progression to becoming cancerous.
Abnormal architecture and arrangement.
What are the different types of spina bifida?
- Spina Bifida Occulta: 1 or more vertebrae don’t form properly
- Meningocele: meninges push out through the spine
- Myelomeningocele: spinal canal remains open along several vertebrae
What’s the difference between congenital, inherited and acquired disorders?
Congenital: present from birth
Inherited: caused by a genetically inherited abnormality
Acquired: caused by a non-genetic environmental factor
What are chromosomal abnormalities?
Chromosomal abnormalities are caused by errors in the number or structure of chromosomes. Some examples of chromosomal abnormalities cause by an error in the number of chromosomes are:
•Down’s syndrome or trisomy 21: The individual has an extra chromosome 21.
•Trisomy 18 or Edwards’s syndrome: The individual has an extra chromosome 18.
•Trisomy 13 or Patau syndrome: The individual has an extra chromosome 13
What is Huntington’s disease?
Early-onset dementia with symptoms of irritability, depression, poor coordination and difficulty in making decisions.
Caused by a mutation which causes there to be 36-120 CAG trinucleotide repeats in the Huntington gene.
What is Progeria?
An autosomal dominant genetic disorder.
Premature symptoms of ageing.
People with progeria have specific features: Growth failure, Macrocephaly (big head), Micrognathia (undersized jaw), Absent or delayed teeth formation, Alopecia (hair loss), Aged-looking skin, Dry, scaly, or thin skin, Loss of body fat, Joint abnormalities.
What are the signs of ageing?
Balding Cataracts - UV-B light causing cross-linking of proteins, causes cloudiness Loss of teeth Senile dementia Hypertension and heart disease Prostatic hyperplasia Degenerative joint diseases Deafness Dermal elastosis - increase in elastin, caused by UV-B which causes protein cross-linking Osteoporosis - bone weakening, increased no. of fractures Diverticular disease of colon Ankle oedema due to heart failure
How is telomere length associated with lifespan?
Telomeres are regions of repetitive nucleotide sequences at each end of a chromosome, which protects the end of the chromosome from deterioration or from fusion with neighbouring chromosomes.
As cells divide, telomeres get shorter.
In humans, average telomere length declines from about 11 kilobases at birth to fewer than 4 kilobases in old age.
Telomere length is paternally inhibited and is associated with paternal lifespan.
What is sarcopenia?
Sarcopenia is the degenerative loss of skeletal muscle mass, quality, and strength associated with aging. The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. Sarcopenia can lead to reduction in functional status and cause significant disability.
What’s the difference between resolution and repair?
Resolution: when you remove initiating factor e.g. infection, alcohol consumption tissue is either undamaged or able to regenerate.
Repair: initiating factor is still present and tissue is damaged and unable to regenerate.
What is lobar pneumonia?
Lobar pneumonia is a form of pneumonia characterized by inflammatory exudate within the intra-alveolar space resulting in consolidation that affects a large and continuous area of the lobe of a lung.
Air spaces become filled with neutrophils but can be cleared with antibiotics.
What is abrasion?
Top layers of skin removed but hair follicles and sweat glands remain. Scab forms over the surface. Epidermis grows out from the adnexa, protected by the scab. Scab falls off.
What are the possible outcomes following a skin wound?
- 1st intention (best outcome): Incision produces a weak fibrin joint which leads to a strong collagen joint through epidermal regrowth and collagen synthesis.
- 2nd intention: missing area of skin/hair follicles/sweat glands. Granulation tissue forms leading to organisation and early fibroid scar and scar contraction. End up with a larger scar.
- Grannulation tissue: new connective tissue and microscopic blood vessels that form on the surface of the wound during the healing process. Grows out from the base.
Which cells can and can’t regenerate?
Cells that can regenerate: hepatocytes, pneumocytes, all blood cells, gut epithelium, osteocytes.
Cells that can’t regenerate: myocardial cells and neurons. Replacement of damaged tissue by fibrosis tissue e.g. pale collagen deposits in heart, gliosis in brain, spinal cord after trauma
What is thrombosis?
Solid mass of blood constituents formed within an inact vascular system during life.
If endothelium is damaged, platelet stick to the side (platelet aggregation) and RBCs get trapped here (thrombus formation). Platelets release chemicals which cause fibrinogen to convert to fibrin creating a mesh.
Positive feedback loop.
What predisposes a thrombus?
Change in vessel wall, blood flow or blood constituents.
What is an embolus?
Mass of material in the vascular system able to become lodged within a vessel and block it.
No blood flow distal to blockage.
What is ischaemia and infarction?
Ischaemia: reduction in blood flow
Infarction: death of cells due to reduction in blood flow
