Pathology Flashcards
(174 cards)
1
Q
Causes of fluctuating cognitive function
A
subdural haematoma cerebral abscess meningioma acute aortic regurgiation hypertensive encephalopathy alcohol intoxication
2
Q
2 types of autopsy
A
hospital autopsy (less than 10%) medico-legal autopsy (over 90%)
3
Q
autopsy requirements
A
consent needed
death certificate needed
4
Q
Deaths referred to coroner
A
presumed natural (cause of death not known/not seen by doctor in last illness) presumed iatrogenic (clinical care - post-operative, anaesthetic, therapeutic complications) presumed unnatural (accident, suicide, industrial (asbestos), unlawful killing, custody death)
5
Q
Who makes referrals?
A
Doctors
Registrar of BDM (Births, Deaths, Marriages)
Police
Relatives
6
Q
Who performs autopsies?
A
Doctors
Histopathologist (hospital and coronial)
Forensic pathologists (coronial)
7
Q
Role of coroner (questions that they need to answer)
A
Who was deceased?
when and where death occurred?
How did they come about their death?
8
Q
What is an autopsy?
A
1) History/scene
2) External exam
3) Evisceration
4) Internal exam
5) Reconstruction
9
Q
Samples taken during autopsy
A
Microbiology Toxicology XRAY Histology Genetics Photographs
10
Q
External exam
A
Identification - Gender, age, jewellery, clothing, body mod
Injuries
11
Q
Evisceration
A
Y-shaped incision Open all body cavities Examine all organs in situ Remove thoracic and abdo organs Remove brain
12
Q
Internal exam
A
Internal organs, nodes, vessels, tracts and central NS
13
Q
What is inflammation?
A
A reaction to injury or infection involving cells such as neutrophils and macrophages
14
Q
When is inflammation bad?
A
Autoimmune
15
Q
Inflammation classification
A
Acute (neutrophils) - sudden, short-duration, resolves usually
Chronic (lymphocytes and macrophages) - Slow onset, long-duration, may never resolve
16
Q
Neutrophil polymorphs
A
Short lived cells, first line
First to act during acute inflammation
Use enzymes to kill bacteria, end up dying during the process resulting in puss
17
Q
Macrophages
A
Long-lived cells Phagocytic Ingest bacteria Carry debris away Present antigen to lymphocytes
18
Q
Lymphocytes
A
Longest lived cells
Produce chemicals which attract other inflammatory cells
Immunological memory
19
Q
Endothelial cells
A
Become sticky in areas of inflammation so inflammatory cells adhere to them
Become porous to allow inflammatory cells into tissues
20
Q
Fibroblasts
A
Long lived
Form collagen in areas of chronic inflammation and repair
21
Q
Acute inflammation examples
A
Acute appendicitis
22
Q
Acute inflammation outcomes
A
Resolution
Discharge of pus
Chronic inflammation
23
Q
Chronic inflammation example
A
TB
24
Q
Granulomas
A
Group of macrophages
Chronic inflammation
25
Treating inflammation
Inhibit prostaglandin synthetase (prostaglandins are chemical mediators of inflammation)
NSAIDs - Aspirin, Ibuprofen etc
Corticosteroids - bind to DNA and upregulate inhibitors of inflammation and downregulate chemical mediators of inflammation
26
LECTURE CATCHUP*
LC*
27
Carcinogenesis
Transformation of normal cells to neoplastic cells through permanent genetic mutations
Apples to malignant neoplasms only
28
Oncogenesis
Benign and malignant tumors
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Crcinogens
Agents known or suspected to cause tumours
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Carcinogenic
Cancer causing
31
Oncogenic
Tumour causing
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Muatgenic
Act on DNA
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Risk of cancer - Environmental
85%
34
Hepatocellular carcinoma
Uncommon in UK/USA
| Common in areas with increased Hep B/C and mycotoxins
35
Oesophageal carcinoma
High incidence in Japan, China, Turkey and Iran
| - Dietary factors (Linhsien chickens and hot tea respectively)
36
Behavioral risks
Lung cancer - smoking
37
Occupational risks
Bladder cancer - Dye and rubber industry
| Scrotal cancer - Chimney sweeps
38
Classes of carcinogens
```
Chemical
Viral
Ionising and non-ionising radiation
Hormones, parasites and mycotoxins
Misc
```
39
Chemical carcinogens
Tend to require conversion from pro-carcinogen to ultimate carcinogen
Enzyme required may be confined to certain organs
Some act directly
40
Chemical carcinogens
Polycyclic aromatic hydrocarbons - Lung and skin cancer - Smoking
Aromatic amines - Bladder cancer - Rubber/dye industry
Nitrosamines - Gut cancer
Alkylating agents - Leukaemia
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Radiant energy
UV light - Melanoma
Xeroderma pigmentosum condition has increased risk
Ionising radiation for long term increases skin cancer in radiographers
Lung cancer in uranium miners
Thyroid cancer in Ukranian children
42
Biological agents
Hormones - Oestrogen - Breast/endometrial cancer
Anabolic steroids - HCC
Mycotoxins - Aflatoxin B1 - HCC
Parasites - cHLOARCHIS SINESIS - Cholangiocarcinoma
Schistosomiasis - Bladder cancer
43
Misc
Asbestos
| Metals
44
Host factors
Race - Increased Oral cancer in SE asia (reverse smoking, betal chewing), Decreased skin cancer in blacks (melanin)
Diet
Age - Increases
Gender - Breast cancer
Premalignant lesions - Colonic polyps, UC.
Transplacental exposure - Diethylstiboestrol - Increased vaginal cancer
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Cancer
Latent interval between exposure and cancer development
46
Tumour
Any abnormal swelling - Neoplasm (tends to be), inflamamtion, hypertrophy, hyperplasia
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Neoplasia
A lesion which is autonomous, abnormal, persistent and is a new growth. It persists after the initiating stimulus has been removed
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Neoplasia
25% of pop
| 20% of all deaths
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Deaths from cancer
Prostate cancer is most common in men, but lung cancer is most common killer
Breast cancer is most common in women though
50
Structure of neplasms
Neoplasm, neoplastic cells, derived from nucleated cells usually monoclonal, growth pattern and synthetic activity related to the parent cell,
Neoplasm, stroma, connective tissue framework, mechanical support, nutrition.
51
Tumour angiogenesis
1) Avascular tumour nodule
2) Vascularised tumour
3) Vascularised tumour with central necrosis
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Neoplasm structure
Tumour cells + stroma
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Classifying neoplasms
Behavioral: Benign/borderline/malignant
Histogenetic: Cell of origin
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Benign neoplasms
```
Localised
Non-invasive
Slow growth rate
Low mitotic activity
Close resemblance to normal tissue
Circumscribed or encapsulated
Necrosis rare
Ulceration rare
Growth on mucosal surfaces often exophytic
```
55
Benign neoplasms concerns
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Pressure on adjacent structures
Obstruct flow
Produce hormones
Transform to malignant neoplasm
Anxiety
```
56
Malignant neoplasms
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Invasive
Metastases
Rapid growth rate
Variable resemblance to normal tissue
Poorly defined/irregular border
Hyperchromatic nuclei
Increased mitotic activity
Necrosis and ulceration common
Growth on mucosal surfaces and skin often endophytic
```
57
Malignant neoplasms concerns
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Destruction of adjacent tissue
Mets
Blood loss from ulcers
Obstruction of flow
Hormone production
Paraneoplastic effects
Anxiety and pain
```
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Histogenetic classifiation
Histogenesis - specific cell of origin of a tumour
| histopathlogyical examination
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nomenclature of neoplasia
neoplasms may arise from epithelial cells, connective tissue, lymphoid tissue
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nomenclature of neoplasms
all neoplasms have suffix -oma
| prefeix depending on behavioural classificaiton and cell type
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Benign epithelial noeplasms
Papilloma - benign tumour of non-glandular, non-secretory epithelium
prefix with cell type of origin e.g. squamous cell papiloma
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benign epithelial neoplasms
adenoma - benign tumour of glandular or secretory epithelium
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malignant epithlial neoplasms
carcinoma - malignant tumour of epithelial cells
prefixed by name of epithelial cell type e.g. trnaslational cell carcinoma
Carcinomas of glandular epithelium - adenocarcinomas
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Benign connective tissue neoplasms
```
Lipoma - adipocytes
Chondroma - cartilage
Osteoma - bone
Angioma - vascular
Angiolipoma - blood and fat cells neoplastic
Rhabdomyoma - sriated muscle
Leiomyoma - smooth muscle
```
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Maligantn connective tissue neoplasms
Liposarcoma - adipose tissue
Rhabdomyosarcoma - striated muscle
Osteosarcoma - bone
etc
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Carcinomas and sarcomas classified further
Degree of differentiation
67
Anaplastic
Where cell type of origin is unknown
68
Some exceptions
Not all -omas are neoplasms: granuloma, tuberculoma, mycetoma
Not all malignant tumours are carcinoma or saroma: melanoma, mesothelioma, lymphoma
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cancer summary
Behaviour: benign or malignant
histogenesis: cell of origin
suffix: -oma denotes neoplasm
prefix: benign or malignant, and cell type
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Carcinoma in situ
Not invaded anywhere
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Invasive carcinoma
Invaded basement membrane
| Can be micro-invasive
72
Cancer growth
Invasion of basement membrane - proteases (matrix metalloproteinases in liver cancer)
Invade bm - cancer cells moving through bm
Invasion of extracellular matrix using proteases, then cell motility again to invade through again.
Move into and travel through lymphatic or blood vessel
Stick to side of vessel wall
Out into extracelllular matrix
Regrowth and create own blood supply (angiogenesis) at metastatic site
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Inhibitors of angiogenesis
Avastin (standard treatment for macular degeneration)
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Routes for mets
Blood vessels
75
Common organ for mets to occur
Any common cancers, sarcomas, often mets to lung
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Colorectal/colon cancer tends to spread to
Liver
| Also anything which drains to portal venous system mets to liver
77
tumours that mets to bone
```
prostate
breast
lung
kidney
thyroid
```
78
lung cancers
non-smoker - adenocarcinoma
| smoker - squamous cells carcinoma
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Chemotherapy
Vinblastine (antimicrotubule agent)
Etoposide
Ifosamide (binds to dna directly and cross links it to prevent replication)
cisplatin does same as ifosamide
80
Chemotherpay
Uusally hits normal cells which are dividing - myelosuppression, hair loss, diarrhoea
Good for fast dividing tumours (lymphomas, acute leukaemias), not for slower dividing ones
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Increase in tumour size
Cell division
| Lack of apoptosis
82
Targeted chemo
more effective
| less se
83
How to find differences between normal and cancerous tissue
gene arrays
proteomics
tissue microarrays
84
How to exploit differences
make a monoclonal ab against growth factor receptors to prevent growth factors binding so no activation signals and no proliferation
Small molecular inhibitor of growth factor receptor, same effects but harder to make
85
Cetuximab
mab on end means monoclonal ab
Chimeric so that body does not identify as foreign
EGFR blocker
86
Herceptin
Chimeric mab against EGFR 2 (Her-2)
Her-2 has a TKI switch
2 Her-2 molecules binding together activates signals for proliferations
Hereceptin mab causes Her-2 protein to be endocytosed and destroyed, this reduces her-2 numbers and so reduces its activity
Lymphocytes then are triggered and join
Her-2 gene is amplified in breast cancer, so Herceptin is used for adjuvant chemo in her2-positive breast cancer
87
How to detect her-2 amplification
FISH - Fluorescent in situ hybridisation
| Immunohistochemistry
88
Anti-PD1
PD1 overexpression in tumours causes immunosuppression
89
Small molecular inhibitors
Gleevec - Inhibits c-kit receptor
| Gefitinib - EGFR TKI inhibitor
90
Transfusion consists of
RBCs
Platelets
Volume (saline)
91
MI treatment (atherosclerosis)
PCI
Stent
Anticoag
92
How to avoid DVT in post surgery
gENERAL PROPHYLAXIS - ted STOCKINGS, HEPARINS
| lONG TERM - IVC cage and anti coag
93
Coroner
Interested in non-natural deaths
94
Several chest infections may indicate
Lung cancer (asbestos, car fumes, soot, smoking)
95
Tissue for diag (lung)
Sputum
bronchoscopy
Pleural biopsy
96
Histology and cytology of lung cancer
Small cell cancer is worse than large cell
97
TNM staging is applied to all tumours
T - Tumour size (larger the grade, larger tumour size)
N - Lymph nodes (Larger grade, further LN spread)
M - Mets (Distant is worse)
98
Resolution vs repair
Resolution - Initiating factor removed, tissue undamaged or able to regenerate
Repair - Initiating factor still present. tissue damaged and unable to regenerate
99
Cells that can regenerate
```
Hepatocytes
Pneumocytes
All blood cells
Gut epithelium
Skin epithelium
Osteocytes
```
100
Skin wounds - Healing by 1st intention
1) Incision
2) Exudation of fibrinogen
3) Weak fibrin join
4) Epidermal regrowth and collagen synthesis
5) Strong collagen join
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Skin wounds - Healing by 2nd intention
1) Tissue loss
2) Granulation tissue
3) Organisation
4) Eary fibrous scar
5) Scar contraction
102
Repair
Replacement of damaged tissue by fibrous tissue
103
Collagen is produced by
Fibroblasts
104
Cells that can't regenerate
Myocardial cells
| Neurones
105
Upper abdo pain
Refer for OGD (Oesophagogastroduodenoscopy)
Suspect gastritis
Check for any inflammation via biopsy
Infection by helicobacter indicated by raised urease levels
Gastrin overproduction - excess acid from body gland gastric cells
Gastritis increases risk of gastric/duodenal ulceration
Treat with antibiotics
106
Types of inflammatory cells
```
Macrophage
Plasma cell
Neutrophil
Lymphocyte
Giant cell
```
107
The inflammatory process also stimulates
Kinin system
Fibrinolytic system
Coagulation system
Complement cascade
108
Scarring
Healing response which seals up the tissues
| But contractures/adhesions alter anatomy and can get worse with time
109
Lymphoma
Malignant neoplasm of lymphoid cells
110
Chemo treatment
Damages fast dividing neoplastic cells but also hits - Hair, marrow and GI tract
111
Thrombosis
1) Normal laminar flow
2) Endothelial cell injury
3) Platelet aggregation
4) Thrombus formation
5) Fibrin deposition
112
Thrombosis
Solid mass of blood constituents formed within intact vascular system during life
113
Thrombosis triad
Change in vessel wall - endo cell injury due to smoking which changes wall and also blood flow
Change in blood flow
Change in blood constituents
114
Aspirin
Inhibits platelet aggregation
115
Embolus
Solid mass in blood being carried through circulation to a place where it gets stuck and blocks the vessel
This solid mass tends to be a thrombus such as a DVT of the leg veins which breaks off and embolises through the large veins and right side of the heart to the lungs
116
Ischaemia
Reduction in blood flow
117
Infarction
Reduction in blood flow with subsequent death of cells
118
Why blood clots don't form all the time
Laminar flow - Cells travel in the centre of arterial vessels and don't touch the sides
Endothelial cells which line vessels are not sticky when healthy
119
Most common type of thrombosis
DVT - Deep Vein Thrombosis (hosital inpatients)
120
Prevention of DVT for inpatients
Mobilisation
Low dose SC heparin
Venous stockings
121
Less common causes of embolus
Air - pressurised systems of IV fluids/bloods
Cholesterol crystals from atheromatous plaques
Tumour
Amniotic fluid in pregnant women
122
Embolism venous route
Embolus which enetrs the venous system will travel to the vena cava, through the right side of the heart and will lodge into the pulmonary arteries
From here it cannot get into the arterial circulation of the heart because the blood vessels in the lung split down to capillary size, so the lung acts as a filter for any venous emboli
123
Ischaemia
Simply a reduction in blood flow to a tissue without any other implications
124
Infarction
Reduction in blood flow to a tissue that is so reduced that it cannot even support mere maintenance of the cells in that tissue so they die
Infarction is usually macroscopic caaused by thrombosis of an artery - such as thrombus in the LAD coronary artery causing infarction of the anterior wall of the left ventricle
125
Organs with dual arterial supply
Less suspectible to infarction
Liver - Portal venous and hepatic artery
Lung - Pulmonary venous and bronchial artery
Brain - COW
126
Coronary artery infarctions
Right CA - Inferior infarct, can also include posterior septum
LAD - Anterior infarct (sudden death)
Circumflex artery - Lateral infarct
127
Regional transmural myocardial infarction
Infarction that is transmural through all cardium layers (endocardium to epicardium layers)
128
Subendocardial myocardial infarction
Infarct of the myocardium that is subendocardial
129
Initial reaction of tissue to injury
Vascular - Dilation of vessels
Exudative - Vascular leakage of protein-rich fluid
Neutrophil polymorphs are charcteristic of cells recruited to the tissue
130
Materials that resist digestion
Keratin
Necrotic bone
Cholesterol crystals
Sodium urate
131
Stroke
Cerebral infarction
132
Heart attack
Myocardial infarction
133
Infarction and ischaemia
Infarction is always due to ischaemia but ischaemia does not always cause infarction
134
Angina
Ischaemia may cause chest pain but no infarction
135
Atheroma
AKA Atherosclerosis
Pathology of arteries involving deposition of lipids in the arterial wall with surrounding fibrosis and chronic inflammation
These plaques can enlarge to occlude the lumen of vessels
Predominant cause of MI and CI
136
Atheroma - Risk factors
```
Raised serum lipids (LDL/triglycerides cause direct damage to endothelial cells)
Hypertension (Shearing force on endothelial cells which are delicate in nature)
Diabetes mellitus (Superoxide anions
Smoking (CO, nicotine)
```
137
Atheroma formation - 2 Processes
```
Endothelial damage (due to lipids, raised BP, smoking)
Chronic inflammation (Macrophages and fibroblasts)
```
138
Prevention/slowing progression of atheromas
Reducing lipids
Reducing BP
Smoking cessation
Low dose aspirin will reduce amount of platelet aggregation at site of endothelial damage
139
Atherosclerosis
Common in high pressure systems such as aorta rather than low pressure systems such as pulmonary arteries
140
Plaque composition
Fibrous tissue
Lipids - cholesterol
Lymphocytes
141
Atherosclerosis - Complications
MI
Cerebral infarct (CI) due to carotid atheroma embolising and causing TIA or CI
Aortic aneurysms - Rupture causes sudden death
Gangrene
142
Apoptosis
Programmed cell death of a single cell
143
Necrosis
Unprogrammed death of a large number of cells due to an adverse event such as infarction, burns, frostbite, etc
144
Apoptosis
Important in normal body function
In the gut, there is a steady turnover of cells with stem cells dividing to produce new cells which mature and differentiate and eventually die by apoptosis
145
Apoptosis
Implemented by Caspases and Bcl2 protein
146
Alternatives to apoptosis for cells
Autophagy
Closing down protein synthesis
Cell cycle arrest
147
Apoptosis
If a cell has a lot of DNA damage then apoptosis will be preferred over the other options
148
Apoptosis process
1) Bcl2 protein and activated Fas receptor signal Caspases
| 2) Caspases cause apoptosis
149
Necrosis example
```
Toxic spider venom
Frostbite
Cerebral infarction
Avascular necrosis of bone
Pancreatitis
```
150
Necrosis types
Coagulative
Liquifactive
Caseous
151
Sickle cell anaemia - Genetic cause
1) Point mutation in the beta-globin chain of haemaglobin
2) Causes the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the 6th position
3) This is a very specific genetic abnormaility
4) This always produces an abnormal haemaglobin which causes RBCs to sickle (deform) when oxygen sats are low
152
Sickle cell anaemia
Single gene disorder - abnormality of a single gene causes disease
153
Polygenic diseases
Genetic diseases resulted from the interaction of several different genes usually on different chromosomes
154
Breast cancer
Polygenic disorder
| BRCA1 and BRCA2 along with many other genes
155
Congenital disease
Born with it (genetic)
156
Rhesus haemolytic disease
In newborns where maternal antibodies attack RBCs of baby in utero
157
Fetal alcohol syndrome
Baby with facial characteristics - Small eye openings, smooth philtrum, thin upper lip
158
Pituitary adenoma
Growth hormone excess
159
Hypertrophy
Increased tissue size due to increased cell size
160
Hyperplasia
Increased tissue size due to increased number of cells
161
Hypertrophy examples
Physiological - Skeletal muscle cells
| Pathological - Myocardium undergoes hypertrophy in patients with raised BP
162
Hyperplasia examples
Physiological - During pregnancy and lactation, the breast epithelial cells respond to increased physiological demands by undergoing hyperplasia
Pathological - Prostate undergoes hyperplasia with age in response to a relative excess of oestrogen stimulation
163
Atrophy
Decrease in size of an organ or tissue
164
Atrophy examples
Physiological - Thymus in early adult life. Genitals, mandible, cerebrum and lymphoid tissue atrophy in later life
Pathological - Occurs as a result of a loss of blood supply, loss of innervation, pressure, lack of nutrition, lack of hormonal stimulation, or as a result of hormonal stimulation
165
Metaplasia
Reversible transformation of a mature differentiated cell type into another fully differentiated cell type
It is an adaptive response to injurous stimuli
166
Metaplasia examples
Transformation of the normal pseudostratified columnar ciliated epithelium ciliated epithelium of the bronchi into squamous epithelium following repeating smoking
167
Dysplasia
Premalignant condition characterised by increased growth, cellular atypia and decreased differentiation
Caused by long exposure to chronic inflammation and carcinogenic substances
168
Dysplasia examples
HPV infection in squamous epithelium of uterine cervix
169
Ageing manifestations
```
Cancer development
Neurodegeneration - Alzheimer's dementia and Parkinson's disease
Osteoarthritis
Hearling loss
Vision loss
Reduced immunity
```
170
Ageing manifestations - Cellular causes
Damage to mitohondrial DNA
Accumulation of toxic by-products of metabolism
Free-radical generation
Time-dependent activation of ageing and death genes
171
Oestrogen and bone relationship
Lack of oestrogen = decreased bone formation and increased bone resorption
172
Neurodegeneration during ageing - mechanisms
Cortical atrophy
Shrinkage of hippocampus
Enlarged ventricles
173
Muscle degeneration
Decreased growth hormone
Decreased testosterone
Increased catabolic cytokines
174
Deaffness - mechanism
Loss of hair cells in cochlear which are unable to regenerate
