Pathology Flashcards
what 3 factors are involved in the process of aging? (ie how well you age?)
genetic factors
environmental factors
manifestation of age related disease
why does cellular aging occur?
progressive decline in the proliferation capacity and life span of the cell
what 7 biochemical and structural changes occur with cellular aging?
mitochondria abnormalities reduced ER distorted Golgi appartus accumulation of lipofusin advanced glycation end products abnormally folded proteins reduced capacity to undertake key biochemical process
what 3 key biochemical processes become less effective with cellular aging?
decreased oxidative phosphorylation
decreased synthesis of key nucleic acids and proteins/enzymes
reduced capacity for nutrient uptake
what causes accumulation of lipofuscin in a cell?
episodes of oxidative damage
describe the life span and metabolic rate of small animals?
shorter life span
high metabolic rate
how are free radicals usually formed?
by-products of oxidative phosphrylation
what is the term used to describe the non-dividing state a cell goes into after a fixed number of cell divisions?
senescence
what happens to Hayflicks number as you get older?
Hayflicks number decreases?
what genetic abnormality is associated with defective DNA helicase and so has a much reduced capacity for rounds of cell division?
Werner’s Syndrome
What are Telomeres?
DNA caps at chromosome ends
what is the DNA sequence of telomeres?
repeated sequences of TTAGGG
what are the 2 functions of telomeres?
- ensure complete replication of genome
2. protect coding sequences at the chromosome ends from damage
what happens in telomere shortening?
incomplete replication of chromosome ends which leads to cell cycle arrest
What is the function of Telomerase?
maintains the telomere length
what is Telomerase made out of?
a RNA-protein complex
the RNA provides the template for telomere maintenance
compare Telomerase activity in germ cells, stem cells and somatic cells?
(germ cells = sperm/egg, somatic cells = every other cell in the body)
telomerase activity is greater in germ cells than stem cells but there is no telomerase activity in somatic cells
what is enzyme is up-regulated in immortalised cells?
telomerase
allows maintenance of telomere length therefore cell cycle will never arrest
where do the genes for longevity in families come from?
mirochondria
maternal inheritance
what is Progeria?
a rare genetic condition causing growth retardation in infancy with macrocephaly and fast developing signs of old age
what causes Progeria?
usually a spontaneous mutation
why do children with Progeria have a life expectancy of late teens to 30?
they develop atherosclerosis very early and die of its consequences eg MI, CVA, heart failure
what occurs in neurogenerative disease? (such as alzheimer type dementia)
frontal and temporal lobe atrophy and compensatory ventricular dilation
formation of senile plaques and neurofibrillary tangles
all causing acceleration of normal aging process
what is osteoporosis?
when bones decline in density causing the patient to become prone to fractures, even with minimal stress
what is osteoarthritis?
degeneration of articular surfaces (“wear and tear”)
what are the 4 factors must be highly functioning to ensure cell integrity?
DNA
Cell membrane
Energy production
Protein synthesis
what type of cells are more susceptible to DNA damages and why?
dividing cells
abnormal (but non-lethal) sequence is inherited by daughter cells and so is recognised as normal, DNA repair mechanisms are by passed
(pemanent cells are more resistant)
what type of turnover do skin and hair cells have?
and what does this mean in regards to acquiring abnormalities?
high cell turnover
highly susceptible to abnormalities
what type of turnover do cardiac cells and adult neurones have?
and what does this mean in regards to acquiring abnormalities?
low cell turnover
resistant to abnormalities
what is the role of p53 genes?
makes a protein that causes apoptosis in cells with DNA damage
if p53 is lost what is more likely to happen?
obtain a malignancy
if a cancer is due to a loss of p53 function how affected is it by drugs?
more likely chemotherapy/drug resistant because many drugs use p53’s apoptosis ability
what 2 major things can cause failure of ion pumps and therefore disruption of ionic concentrations and osmolarity?
structural defect of the ion pump defective mitochondria (energy dependent)
what can happen to the cell membranes of people with high levels of cholesterol?
excessive cholesterol can cause the membrane to harden
what are free radicals?
highly reactive charges species which are generated by the body in normal metabolism (oxidative phosphorylation) or infection response. They can also be produced by drugs (eg paracetamol)
what can free radicals do to the lipid membrane?
bind to and peroxidise and cross link components of the membrane thus damaging membrane integrity
what are anti-oxidants?
molecules which scavenge free radicals and prevent damage to cell membrae through lipid perocidation
with regards to number of free radicals, what occurs when oxygen content of the air increases?
free radical content increases- this is what is meant by oxygen toxicity
why are anti-oxidation techniques used in reperfusion procedures?
as blood rushes back to an area of the body, many free radicals are produced- reperfusion injury
what 5 things determine the severity of tissue injury?
duration of stimuli persistency nature of stimuli proportion of cells affected regenerative capacity topography
what is topography?
the microanatomy of structures affected by an injury
what type of regenerative capacity do hepatocytes and kidney cells have?
high regenerative capacity
what type of regenerative capacity do permanent cells such as cardiac cells and adult neurones have?
low regenerative capacity
what happens to ATPase pumps and therefore the osmolarity of the cell if the cell is hypoxic?
ATPase pumps are shed to reduce ATP consumption rate and therefore ionic concentrations will be altered and cells swell with fluid intake
which 2 ways can cells die?
apoptosis
necrosis
in apoptosis how does the cell die?
a stimulus causes the cell to die by collapsing and fragmenting
where does normal apoptosis occur?
loss of webbed fingers and toes, palate fusion
embryonic development
are apoptosis and necrosis pathological or physiological?
apoptosis can be physiological or pathological
necrosis is always pathological
what are the 6 patterns of necrosis?
coagulative colliquative caseous gangrenus fibrinoid fat necrosis
what happens in coagulative necrosis?
proteins of of cell coagulate
what is a common reason for coagulative necrosis?
prolonged cardiac ischaemia
what happens in colliquative necrosis?
phosphlipids turn to liquid
where in the body does colliquative necrosis occur?
brain
what is caseous necrosis a diagnosis of?
TB
what happens in gangrenous necrosis?
cell death by apoptosis and then infection caused by anaerobic bacteria
what happens in fat necrosis?
fat cells die often due to trauma
what happens in fibrinoid necrosis?
necrosis which causes a fibrin and immune complex deposits
what are the 2 types of metabolic disorders?
inherited
acquire
what is usually the pattern of inheritance for inherited metabolic disorders?
aotomal recessive
what do metabolic disorders usually cause?
a defective enzyme leading to an increased substrate metabolite and a decreased product metabolism and therefore the rest of the molecules in the pathway are also decreased
what is phenylketonuria a deficiency of?
phenylalanine hydroxylase
what does phenylalanine hydroxylase do?
converts phenylalanine from dietary protein to tyrosine
what is cretinism a deficiency of?
the enzyme that converts tyrosine into thyroid hormones
what is tyrosinosis a deficiency of?
the enzyme that converts tyrosine into homogenitisic acid
what is albinism a deficiency of?
the enzyme that converts tyrosine what iinto melanin
what is alkaptonuria a deficiency of?
the enzyme the breaks down homogenitisic acid into carbon dioxide and water
what is the main problem that results from phenylketonuria?
accumulation of phenylalanine which causes brain toxicity and mental retardation
how can phenylketonuria be tested for?
guthrie test
what is the treatment for phenylketonuria?
phenylalanine free diet
why do phenylketonuria patients have fair skin and blue eyes?
because they cant produce tyrosine and therefore cant produce melanin
what are the 2 phases of cellular injury?
reversible
irreversible
what are the 4 characteristics of irreversible damage?
severe damage to cell membranes
severe damage to mitochondria
leakage of enzymes
nuclear changes
what 4 things can cause cell membrane damage?
progressive loss of phospholipids
lipid breakdown products
reactive oxygen species
cytoskeletal abnormalities
what are the differences between apoptosis and necrosis in terms of the cells they affect?
apoptosis affects scattered cells
necrosis affects sheets of cells
what are the differences between apoptosis and necrosis in terms of cell osmolarity?
apoptosis causes the cells to shrink
necrosis causes the cells to swell
what are the differences between apoptosis and necrosis in terms of inflammation?
apoptosis: no inflammtion
necrosis: inflammation
which type of cell death is energy dependent?
apoptosis
what 2 types of molecules are involved in the biochemical regulation of apoptosis?
inducers
inhibitors
what are the 3 groups of apoptosis inhibitors?
growth factors
cell matrix components
viral proteins
what are 7 inducing causes of apoptosis?
withdrawal of growth factors loss of matrix attachment viruses free radicals ionising radiation DNA damage Fas ligand/ CD95 interaction
what disorders cause increased apoptosis?
AIDS
neurodegenerative disorders
reperfusion injury
what disorders cause decreased apoptosis?
neoplasia
auto-immune disease
what is the outcome of incomplete repair?
repair: scarring
what is the outcome of complete repair?
regeneration: restitution
what are the 3 cell types?
with regards to the multiplication
liable eg GI tract and bone marrow
stable eg hepatocytes and endothelium
permanent eg neurones and skeletal muscle
what is the pool of cells which replace any cells that are lost?
stem cells
where are stem cells located?
in discrete compartments
what happens when labile and stable cells die?
proliferation to replace lost cells
what happens when permanent cells die?
proliferation to replace lost cells isn;t possible
what happens when restitution isnt possible?
repair with scarring
when is restitution not possible?
when the tissue architecture is damaged
what needs to be preserved for restitution to occur?
tissue architecture
describe the repair (with scarring) process?
injury to tissue architecture
formution of granulation tissue
organisation (ie fibrosis)
fibrous scar matures and contracts
what is the fibrous scar made of?
collagen
what is the important precursor to repair of damaged tissue?
granulation tissue
what forms in granulation tissue?
fragile vascular channels
what type of scar has closely apposed edges, minimal granulation tissue and minimal fibrosis?
surgical scar
what type of scar has edges that are widely separated, prominent granulation tissue and prominent fibrosis?
ulcerated scar
why does the wound contract?
caused by the myofibroblasts to minimise the volume of the wound
what problem can wound contraction cause?
stricture or stenosis
ie in GI tract of CBD
what are the 2 types of excessive scar formation?
hypertrophic scar
keloid
what is resolution?
the complete restoration of the tissues to normal after an episode of acute inflammation- ideal scenario
what type of inflammation can resolution occur after?
acute inflammation
NOT chronic
what are the 4 factors favouring resolution?
- minimal cell death (tissue architecture retained)
- cells have a regenerative capcity eg hepatocytes
- rapid destruction of causal agent
- rapid removal of fluid/debris by a good local vascular drainage
what is suppuration?
the formation of pus
what is pus made out of?
living cells dying cells dead neutrophils cellular debris bacteria
what happens when there is tissue archeticture destruction and abundant neutrophils after an episode of acute inflammation?
abscess formation (tissue destruction plus pus)
what needs to be done to an abscess?
surgical procedure to remove, otherwise continues to stimulate inflammation and is unlikely to heal on its own
what is organisation?
replacement of damaged tissue by granulation tissue?
what are the 3 factors favouring organisation instead of resolution?
large amounts of fibrin formed
substantial necrosis
exudate and debris cannot be removed or discharged
what are the 2 pathways to chronic inflammation?
- primary chronic inflammation (most common)
2. chronic inflammation secondary to acute inflammation
what cells are characteristical of acute inflammation?
neutrophil polymorphs
what cells are characteristical of chronic inflammation?
macrophages, plasma cells, lymphocytes fibroblasts
what are the predominant features in repair?
angiogenesis followed by fibroblast proliferation and collagen synthesis
whate cells are characteristical of the intermediate phase between acute and chronic phases?
eosinophils
what 3 reasons can be given for the progression from acute to chronic inflammation?
- indigestible substances (eg glass and suture material) ie causal agent isn’t removed
- deep seated supprative inflammation where drainage is delayed of inadequate
- recurrent episodes of acute inflammation
what happens to deep seated supprative inflammation where drainage is delayed or inadequate?
thick abcess walls composed of granulation tissue form which will fail to come together after drainage and eventually a fibrous scar will form
what is an osteomyelitis?
a chronic abscess which is extremely difficult to eradicate
what 5 factors favour primary chronic inflammation?
- resistance of infective agent to phagocytosis and intracelular killing
- foreign body reactions to endogenous materials
- foreign body reactions to exogenous materials
- some autoimmune diseases
5 primary granulomatous disease
what is an endogenous material?
a material that is made in the body but is present in a site it shouldn’t be
what are 5 possible macroscopic appearances of chronic inflammation?
- chronic ulcer
- chronic abscess cavity
- thickening of the wall of a hollow viscous by fibrous tissue
- granulomatous inflammation
- fibrosis
what is a chronic ulcer?
when mucosa is breached, ulcer base lined by grnulation tissue, fibrous tissue extends through muscle layers
what is a granuloma?
an aggergate of epitheloid histocytes
what is a histocyte?
a macrophage present in connective tissue, mainly secretory function, little phagocytic function
what are the 5 causes of granulomatous disease?
1. specific infections (mycobacteria shistosomiasis) 2, foreign bodies (endo/exogenous) 3. chemicals 4. drugs 5. idiopathic
what type of antibodies to patients with Type 1 diabetes contain?
Type 2 dont contain
anti-islet antibodies
Which type of diabetes is HLA linked?
type 1
what is the pathogenesis of type 2 diabetes?
target cell becomes unresponsive to the insulin being secreted
what is the pathogenesis of type 1 diabetes?
anti-islet antibodies form imune complexes with islet B cells causing islet cell destruction and failure of insulin secretion
what type of disease is obseity?
an acquired metabolic disease
what are the 9 risk factors for atheroma?
family history male (or post-menopausal women) smoking hypertension diabetes plasma lipids obesity age geography
what is the progression from fatty streak on the epithelium to complicated atheroma?
fatty streak
fibrofatty plaque
proliferative atheroma
complicated atheroma
what are the 5 complications of atheroma?
thrombosis aneurysm dissection (a tear in the wall) embolism ischaemia
what is a thrombus?
a solid mass of blood constituents formed within the blood vessel?
what are virschows triad? (risk factors for a thrombus)
damage to the vessel wall
change in blood flow
change in blood constituents
what damage to the vessel wall predisposes to a thrombus?
loss of endothelial surface
inflammation
what change in blood flow predisposes to a thrombus?
stasis (ie not moving for a long period of time, long-haul flights, surgery)
turbulence (ie hypertension)
what change in blood constituents predisposes to a thrombus?
hypercoaguability
caused by smoking, obesity, contraceptive pill use, pregnancy, cancer
what is an embolism?
a mass of material in the vascular system moving from its site of origin to lodge in the vessels in a distant site
what 7 types of embolism can occur?
thromboembolsim fat embolism atheroembolism tumour embolism infective amniotic fluid air embolism
what is an infarction?
zonal necrosis due to sudden occlusion of blood supply (lack of oxygen and nutrients)
