Pathology Flashcards
(141 cards)
1
Q
what 3 factors are involved in the process of aging? (ie how well you age?)
A
genetic factors
environmental factors
manifestation of age related disease
2
Q
why does cellular aging occur?
A
progressive decline in the proliferation capacity and life span of the cell
3
Q
what 7 biochemical and structural changes occur with cellular aging?
A
mitochondria abnormalities reduced ER distorted Golgi appartus accumulation of lipofusin advanced glycation end products abnormally folded proteins reduced capacity to undertake key biochemical process
4
Q
what 3 key biochemical processes become less effective with cellular aging?
A
decreased oxidative phosphorylation
decreased synthesis of key nucleic acids and proteins/enzymes
reduced capacity for nutrient uptake
5
Q
what causes accumulation of lipofuscin in a cell?
A
episodes of oxidative damage
6
Q
describe the life span and metabolic rate of small animals?
A
shorter life span
high metabolic rate
7
Q
how are free radicals usually formed?
A
by-products of oxidative phosphrylation
8
Q
what is the term used to describe the non-dividing state a cell goes into after a fixed number of cell divisions?
A
senescence
9
Q
what happens to Hayflicks number as you get older?
A
Hayflicks number decreases?
10
Q
what genetic abnormality is associated with defective DNA helicase and so has a much reduced capacity for rounds of cell division?
A
Werner’s Syndrome
11
Q
What are Telomeres?
A
DNA caps at chromosome ends
12
Q
what is the DNA sequence of telomeres?
A
repeated sequences of TTAGGG
13
Q
what are the 2 functions of telomeres?
A
- ensure complete replication of genome
2. protect coding sequences at the chromosome ends from damage
14
Q
what happens in telomere shortening?
A
incomplete replication of chromosome ends which leads to cell cycle arrest
15
Q
What is the function of Telomerase?
A
maintains the telomere length
16
Q
what is Telomerase made out of?
A
a RNA-protein complex
the RNA provides the template for telomere maintenance
17
Q
compare Telomerase activity in germ cells, stem cells and somatic cells?
(germ cells = sperm/egg, somatic cells = every other cell in the body)
A
telomerase activity is greater in germ cells than stem cells but there is no telomerase activity in somatic cells
18
Q
what is enzyme is up-regulated in immortalised cells?
A
telomerase
allows maintenance of telomere length therefore cell cycle will never arrest
19
Q
where do the genes for longevity in families come from?
A
mirochondria
maternal inheritance
20
Q
what is Progeria?
A
a rare genetic condition causing growth retardation in infancy with macrocephaly and fast developing signs of old age
21
Q
what causes Progeria?
A
usually a spontaneous mutation
22
Q
why do children with Progeria have a life expectancy of late teens to 30?
A
they develop atherosclerosis very early and die of its consequences eg MI, CVA, heart failure
23
Q
what occurs in neurogenerative disease? (such as alzheimer type dementia)
A
frontal and temporal lobe atrophy and compensatory ventricular dilation
formation of senile plaques and neurofibrillary tangles
all causing acceleration of normal aging process
24
Q
what is osteoporosis?
A
when bones decline in density causing the patient to become prone to fractures, even with minimal stress
25
what is osteoarthritis?
degeneration of articular surfaces ("wear and tear")
26
what are the 4 factors must be highly functioning to ensure cell integrity?
DNA
Cell membrane
Energy production
Protein synthesis
27
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)
28
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
29
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
30
what is the role of p53 genes?
makes a protein that causes apoptosis in cells with DNA damage
31
if p53 is lost what is more likely to happen?
obtain a malignancy
32
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
33
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)
```
34
what can happen to the cell membranes of people with high levels of cholesterol?
excessive cholesterol can cause the membrane to harden
35
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)
36
what can free radicals do to the lipid membrane?
bind to and peroxidise and cross link components of the membrane thus damaging membrane integrity
37
what are anti-oxidants?
molecules which scavenge free radicals and prevent damage to cell membrae through lipid perocidation
38
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
39
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
40
what 5 things determine the severity of tissue injury?
```
duration of stimuli persistency
nature of stimuli
proportion of cells affected
regenerative capacity
topography
```
41
what is topography?
the microanatomy of structures affected by an injury
42
what type of regenerative capacity do hepatocytes and kidney cells have?
high regenerative capacity
43
what type of regenerative capacity do permanent cells such as cardiac cells and adult neurones have?
low regenerative capacity
44
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
45
which 2 ways can cells die?
apoptosis
| necrosis
46
in apoptosis how does the cell die?
a stimulus causes the cell to die by collapsing and fragmenting
47
where does normal apoptosis occur?
loss of webbed fingers and toes, palate fusion
| embryonic development
48
are apoptosis and necrosis pathological or physiological?
apoptosis can be physiological or pathological
| necrosis is always pathological
49
what are the 6 patterns of necrosis?
```
coagulative
colliquative
caseous
gangrenus
fibrinoid
fat necrosis
```
50
what happens in coagulative necrosis?
proteins of of cell coagulate
51
what is a common reason for coagulative necrosis?
prolonged cardiac ischaemia
52
what happens in colliquative necrosis?
phosphlipids turn to liquid
53
where in the body does colliquative necrosis occur?
brain
54
what is caseous necrosis a diagnosis of?
TB
55
what happens in gangrenous necrosis?
cell death by apoptosis and then infection caused by anaerobic bacteria
56
what happens in fat necrosis?
fat cells die often due to trauma
57
what happens in fibrinoid necrosis?
necrosis which causes a fibrin and immune complex deposits
58
what are the 2 types of metabolic disorders?
inherited
| acquire
59
what is usually the pattern of inheritance for inherited metabolic disorders?
aotomal recessive
60
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
61
what is phenylketonuria a deficiency of?
phenylalanine hydroxylase
62
what does phenylalanine hydroxylase do?
converts phenylalanine from dietary protein to tyrosine
63
what is cretinism a deficiency of?
the enzyme that converts tyrosine into thyroid hormones
64
what is tyrosinosis a deficiency of?
the enzyme that converts tyrosine into homogenitisic acid
65
what is albinism a deficiency of?
the enzyme that converts tyrosine what iinto melanin
66
what is alkaptonuria a deficiency of?
the enzyme the breaks down homogenitisic acid into carbon dioxide and water
67
what is the main problem that results from phenylketonuria?
accumulation of phenylalanine which causes brain toxicity and mental retardation
68
how can phenylketonuria be tested for?
guthrie test
69
what is the treatment for phenylketonuria?
phenylalanine free diet
70
why do phenylketonuria patients have fair skin and blue eyes?
because they cant produce tyrosine and therefore cant produce melanin
71
what are the 2 phases of cellular injury?
reversible
| irreversible
72
what are the 4 characteristics of irreversible damage?
severe damage to cell membranes
severe damage to mitochondria
leakage of enzymes
nuclear changes
73
what 4 things can cause cell membrane damage?
progressive loss of phospholipids
lipid breakdown products
reactive oxygen species
cytoskeletal abnormalities
74
what are the differences between apoptosis and necrosis in terms of the cells they affect?
apoptosis affects scattered cells
| necrosis affects sheets of cells
75
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
76
what are the differences between apoptosis and necrosis in terms of inflammation?
apoptosis: no inflammtion
necrosis: inflammation
77
which type of cell death is energy dependent?
apoptosis
78
what 2 types of molecules are involved in the biochemical regulation of apoptosis?
inducers
| inhibitors
79
what are the 3 groups of apoptosis inhibitors?
growth factors
cell matrix components
viral proteins
80
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
```
81
what disorders cause increased apoptosis?
AIDS
neurodegenerative disorders
reperfusion injury
82
what disorders cause decreased apoptosis?
neoplasia
| auto-immune disease
83
what is the outcome of incomplete repair?
repair: scarring
84
what is the outcome of complete repair?
regeneration: restitution
85
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
86
what is the pool of cells which replace any cells that are lost?
stem cells
87
where are stem cells located?
in discrete compartments
88
what happens when labile and stable cells die?
proliferation to replace lost cells
89
what happens when permanent cells die?
proliferation to replace lost cells isn;t possible
90
what happens when restitution isnt possible?
repair with scarring
91
when is restitution not possible?
when the tissue architecture is damaged
92
what needs to be preserved for restitution to occur?
tissue architecture
93
describe the repair (with scarring) process?
injury to tissue architecture
formution of granulation tissue
organisation (ie fibrosis)
fibrous scar matures and contracts
94
what is the fibrous scar made of?
collagen
95
what is the important precursor to repair of damaged tissue?
granulation tissue
96
what forms in granulation tissue?
fragile vascular channels
97
what type of scar has closely apposed edges, minimal granulation tissue and minimal fibrosis?
surgical scar
98
what type of scar has edges that are widely separated, prominent granulation tissue and prominent fibrosis?
ulcerated scar
99
why does the wound contract?
caused by the myofibroblasts to minimise the volume of the wound
100
what problem can wound contraction cause?
stricture or stenosis
| ie in GI tract of CBD
101
what are the 2 types of excessive scar formation?
hypertrophic scar
| keloid
102
what is resolution?
the complete restoration of the tissues to normal after an episode of acute inflammation- ideal scenario
103
what type of inflammation can resolution occur after?
acute inflammation
| NOT chronic
104
what are the 4 factors favouring resolution?
1. minimal cell death (tissue architecture retained)
2. cells have a regenerative capcity eg hepatocytes
3. rapid destruction of causal agent
4. rapid removal of fluid/debris by a good local vascular drainage
105
what is suppuration?
the formation of pus
106
what is pus made out of?
```
living cells
dying cells
dead neutrophils
cellular debris
bacteria
```
107
what happens when there is tissue archeticture destruction and abundant neutrophils after an episode of acute inflammation?
```
abscess formation
(tissue destruction plus pus)
```
108
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
109
what is organisation?
replacement of damaged tissue by granulation tissue?
110
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
111
what are the 2 pathways to chronic inflammation?
1. primary chronic inflammation (most common)
| 2. chronic inflammation secondary to acute inflammation
112
what cells are characteristical of acute inflammation?
neutrophil polymorphs
113
what cells are characteristical of chronic inflammation?
macrophages, plasma cells, lymphocytes fibroblasts
114
what are the predominant features in repair?
angiogenesis followed by fibroblast proliferation and collagen synthesis
115
whate cells are characteristical of the intermediate phase between acute and chronic phases?
eosinophils
116
what 3 reasons can be given for the progression from acute to chronic inflammation?
1. indigestible substances (eg glass and suture material) ie causal agent isn't removed
2. deep seated supprative inflammation where drainage is delayed of inadequate
3. recurrent episodes of acute inflammation
117
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
118
what is an osteomyelitis?
a chronic abscess which is extremely difficult to eradicate
119
what 5 factors favour primary chronic inflammation?
1. resistance of infective agent to phagocytosis and intracelular killing
2. foreign body reactions to endogenous materials
3. foreign body reactions to exogenous materials
4. some autoimmune diseases
5 primary granulomatous disease
120
what is an endogenous material?
a material that is made in the body but is present in a site it shouldn't be
121
what are 5 possible macroscopic appearances of chronic inflammation?
1. chronic ulcer
2. chronic abscess cavity
3. thickening of the wall of a hollow viscous by fibrous tissue
4. granulomatous inflammation
5. fibrosis
122
what is a chronic ulcer?
when mucosa is breached, ulcer base lined by grnulation tissue, fibrous tissue extends through muscle layers
123
what is a granuloma?
an aggergate of epitheloid histocytes
124
what is a histocyte?
a macrophage present in connective tissue, mainly secretory function, little phagocytic function
125
what are the 5 causes of granulomatous disease?
```
1. specific infections (mycobacteria shistosomiasis)
2, foreign bodies (endo/exogenous)
3. chemicals
4. drugs
5. idiopathic
```
126
what type of antibodies to patients with Type 1 diabetes contain?
Type 2 dont contain
anti-islet antibodies
127
Which type of diabetes is HLA linked?
type 1
128
what is the pathogenesis of type 2 diabetes?
target cell becomes unresponsive to the insulin being secreted
129
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
130
what type of disease is obseity?
an acquired metabolic disease
131
what are the 9 risk factors for atheroma?
```
family history
male (or post-menopausal women)
smoking
hypertension
diabetes
plasma lipids
obesity
age
geography
```
132
what is the progression from fatty streak on the epithelium to complicated atheroma?
fatty streak
fibrofatty plaque
proliferative atheroma
complicated atheroma
133
what are the 5 complications of atheroma?
```
thrombosis
aneurysm
dissection (a tear in the wall)
embolism
ischaemia
```
134
what is a thrombus?
a solid mass of blood constituents formed within the blood vessel?
135
what are virschows triad? (risk factors for a thrombus)
damage to the vessel wall
change in blood flow
change in blood constituents
136
what damage to the vessel wall predisposes to a thrombus?
loss of endothelial surface
| inflammation
137
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)
138
what change in blood constituents predisposes to a thrombus?
hypercoaguability
| caused by smoking, obesity, contraceptive pill use, pregnancy, cancer
139
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
140
what 7 types of embolism can occur?
```
thromboembolsim
fat embolism
atheroembolism
tumour embolism
infective
amniotic fluid
air embolism
```
141
what is an infarction?
zonal necrosis due to sudden occlusion of blood supply (lack of oxygen and nutrients)
