Pathology Flashcards
1
Q
Thrombosis
A
formation of a solid mass from blood constituents in
an intact vessel in a living person
2
Q
1st stage of thrombosis
A
platelet aggregation. Platelets release chemicals when they aggregate which cause other platelets to stick to them and also which start off the cascade of clotting proteins in the blood
3
Q
+ive or -ive feeback loop- platelet aggregation
A
postive
4
Q
2nd stage of thrombosis formation
A
Once the clotting cascade has started there is formation of the large protein molecule fibrin which makes a mesh in which red blood cells can become entrapped
5
Q
why dont blood clots form all the time
A
- 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
6
Q
How does smoking cause thrombosis
A
cigarette smoking causing endothelial cell injury (change in vessel wall and change in blood flow over the injured/absent cells)
7
Q
How to prevent risk of thrombosis in hospital?
A
early mobilisation after operation, low dose subcutaneous heparin
8
Q
How does aspirin reduce the risk of thrombosis?
A
aspirin inhibits platelet aggregation
9
Q
How does COVID cause thrombotic events?
A
Causes changes in clotting factors that causes thrombosis, leading to micro-thrombi in vessels
10
Q
Embolus
A
mass of material in vascular system that becomes stuck in a vessel, blocking it
11
Q
Most common embolus
A
Thrombus, ie DVT in legs breaking off and embolising through the large veins and right side of the heart to the lungs
12
Q
Less common causes of embolus
A
- air (be careful with pressurised systems of intravenous fluids/blood especially in infants and children)
- cholesterol crystals (from atheromatous plaques)
- tumour
- amniotic fluid (rare in pregnant women with precipitate labour)
- fat (severe trauma with multiple fractures)
13
Q
Effects of thrombosis or embolus
A
Reduction in blood flow, causing reduction of O2 to surrounding cells, leading to ischemia
14
Q
Ischaemia
A
a reduction blood flow to a tissue without any other implications
15
Q
Infacrtion
A
reduced blood flow, leading to cell death
16
Q
Why are certain organs less prone to infarction
A
dual arterial supply so are much less susceptible to infarction:
liver - with portal venous and hepatic artery supplies,
-lung - with pulmonary venous and bronchial artery supplies,
-brain around the circle of Willis with multiple arterial supplies
17
Q
Resolution
A
- initiating factor removed
-tissue undamaged or able to regenerate
18
Q
Repair
A
- initiating factor still present
-tissue damaged or unable to regenerate
-replacement of damaged tissue by fibrous tissue
19
Q
Can the liver regenerate?
A
Yes! as long as not too much liver is removed so the patient dies of liver disease
20
Q
Why don’t alcoholics livers regenerate?
A
Initiating factor constantly present due to constant alcohol abuse, so repair occurs not resolution
21
Q
Why can lungs regenerate after lobar pneumonia
A
Pneumocytes can regenerate, no damage to alveoli walls
22
Q
Does repair or resolution occur after severe COVID?
A
If alveoli walls are damaged as a result severe covid, repair occurs in lungs
23
Q
Most superficial skin wound
A
Abrasion- only removed top layer of epidermis, basal cells still present
24
Q
Healing by 1st intention
A
Edges of skins brought together, reduces risk of infection. Fibrinogen first brings skins together, then collogen strengthens and epidermis reforms
25
Healing by secondary intention
sides of the wound are not opposed, therefore healing must occur from the bottom of the wound upwards
26
Cells that can regenerate
* hepatocytes (liver)
* pneumocytes (lungs)
* all blood cells
* gut epithelium
* skin epithelium
* osteocytes (bones)
27
Cell that don't regenerate
* myocardial cells
* neurones
28
Man aged 30 takes a large overdose paracetamol overdose and doesn’t come to hospital for 2 days. He spends a few days on ITU with liver failure but then recovers.
What will be happening in his liver -
resolution or repair?
resolution, Only overdose once, so provided he doesn't die of liver damage, his liver should regenerate
29
A child aged 3 falls off a climbing
frame onto his hand, he fractures his
clavicle. He has his arm in a sling for
4 weeks and is very good about
keeping it in the sling
What will be happening in his
clavicle - resolution or repair?
Resolution- provide child keeps arms in sling as osteocytes regenerate
30
Atherosclerosis
accumulation of fibrolipid plaques in systemic (as opposed to pulmonary) arteries
31
Risk of Atherosclerosis
narrowing of arteries reduces the blood flow to important areas e.g. myocardial infarction in the heart
32
Risk factors of atherosclerosis
* hypertension
* hyperlipidaemia (too many lipids (fats) in your blood)
* cigarette smoking
* poorly-controlled diabetes mellitus
higher in more social deprived areas
33
Do you find atheroslcerosis in the pulmonary arteries
No, blood pressure is lower
34
Current atherosclerosis theory
Endothelial cell damage theory
* endothelial cells are delicate
* easily damaged by cigarette smoke, shearing forces at
arterial divisions, hyperlipidaemia, glycosylation products
* cumulative damage leads to endothelial ulceration, microthrombi, eventual development of established atherosclerotic plaques
35
How does hypertension lead to atherosclerosis
Shearing forces on endothelial cells
36
How does smoking lead to atherosclerosis
Free radicals, nicotine and CO damage endothelial cells
37
How does diabetes lead to atherosclerosis
Superoxide anions and glycosylation products damage endothelial cells
38
How does hyperlipidaemia lead to atherosclerosis
direct damage to endothelial cells
39
Atherosclerosis feedback loop
Positive feedback loop. Damage to endothelium, leads to thrombi healing over, causes increased narrowing, higher BP, causes more damage...
39
Complications of atherosclerosis
Consequences of blocked pluming, occlusion of blood vessel leading to ischemia and possibly infarction
40
Apoptosis
Programmed individual cell death.
41
What causes apoptosis?
DNA damage detected, cell triggers a series of proteins which lead to the release of enzymes (caspases) that auto digest the cell
42
Importance of apoptosis for healthy function
* Development - removal of cells during development e.g. interdigital webs
* Cell turnover - removal of cells during normal turnover e.g. cells in the intestinal villi at the tips, to be replaced by cells from below
43
Apoptosis in disease
* Cancer - cells in tumours often don’t apoptose when they would have been expected to which results in increase in the tumour size and accumulation of genetic mutations. Often this is due to mutations in the P53 gene so the p53 protein can no longer detect DNA damage and instigate apoptosis.
* HIV - the HIV virus can induce apoptosis. It can induce apoptosis in CD4 helper cells which reduces their numbers enormously to produce an immunodeficient state.
44
Necrosis
Traumatic cell death- wholesale destruction of large numbers of cells by some external factor
45
Apoptosis vs Necrosis
Apoptosis is programmed cell death. Necrosis is traumatic cell death by external factor
46
Clinical Example of Necrosis
* Infarction due to loss of blood supply e.g. myocardial infarction, cerebral infarction, avascular necrosis of bone
* Frostbite
* Toxic venom from reptiles and insects
* Pancreatitis
47
Spina bifida occulta
Missing a spinus process, wouldn't notice unless CT scan performed
48
Meningocele
Outpouring sac filled with fluid, n can need to be fixed by surgery, minor disability can occur
49
Myelomeningocele
Outpouring sac containing spinal cord, leads to paralysis
50
Congenital
Present at birth, not always genetic ie club foot
51
Inherited
Caused by an inherited genetic abnormality
52
Chromosomal Abnormalities
Incorrect number of chromosomes inherited, ie downs syndrome, 3 chromosome 21's inherited
53
Medellin Inheritance
Single gene mutation causes problem
54
Autosomal inheritance
On paired chromosome except sex chromosomes
55
Autosomal dominace
Only one dominant allele needed to express problem
56
Autosomal recessive
2 recessives alleles needed to express problem
57
Polygenetic Inheritance
Variation in several genes lead to increased risk of problem
58
Acquired
Caused by non-genetic environmental factors
59
Are inherited diseases always congenital?
No, ie Huntington's disease
60
Can acquired disease be congenital?
Yes, ie fetal alcohol syndrome
61
hypertrophy
increase in size of a tissue caused by increase in size of the constituent cells, usually occurs organs when cells cannot divide, ie skeletal and cardiac muscle
62
hyperplasia
increase in size of a tissue caused by an increase in number of constituent cells, usually occurs in organs that can regenerate, ie gut, skin, smooth muscle ect
63
Common conditions caused by hyperplasia
prostate enlargement as a result of smooth muscle hyperplasia
endometrial hyperplasia, often as a result of hormone imbalance
64
Atrophy
decrease in size of a tissue by a decrease in number of constituent cells and/or a decrease in their size
65
Common atrophy conditions
Cerebral atrophy can be a result of Alzheimer's
Muscle atrophy, can be a result of lack of use after immobilization
Optic atrophy
66
Metaplasia
change in differentiation of a cell from one fully-differentiated type to another fully-differentiated cell
67
Common metaplasia condtions
Bronchi of smokers, ciliated columnar epithelium to squamous epithelium
Barrett's oesophagus, squamous epithelium to columnar epithelium as result of regular stomach acid exposure
68
Dysplasia
imprecise term for the morphological change seen in cell in the progression of becoming cancer, can be used to refer to a developmental abnormality
69
What is found at the end of chromosomes?
Telomeres, region of repetitive DNA
70
Common conditions associated with aging
Dermal elastosis, osteoporosis, cataracts, dementia, sarcopenia, deafness
71
Dermal elastosis
Skin aging, wrinkling, due to cross linking of proteins
72
Cataracts
Protein cross linking in eye lens leading to them becoming opaque
73
Osteoporosis
Increased bone reabsorption, leading to weaker, more brittle bones, more common in woman after the menopause due to hormone imbalance
74
Sarcopenia
Decrease in muscle mass with age, mobility problems (falls, getting up and around) after after losing a lot muscle
75
Deafness
Loss of hair cells in cochlea, these cells do not regenerate
76
Features of acute inflammation
Redness, heat, swelling, pain, loss of function
77
Key cells involved in acute inflammatory process
Neutrophils, multi-lobular nuclease
78
NSAIDS
Non-steroidal anti-inflammatory drugs
79
Common side effect of chronic NSAID use
Gastritis. NSAIDs diminish protective mucin secretions. They also cause exfoliation of the surface epithelium. This results in damage to the surface epithelium, eliciting an acute inflammatory response
80
Most common Bacteria that causes gastritis
Helicobacter pylori
81
Common signs of sepsis
High temp, HR is fast, BP is low, Confusion
82
Chronic inflammation, causes and cells associated
May be a progression from acute inflammation. May represent a primary disease process. Lymphocytes, macrophages, plasma cells and eosinophils are associated with chronic inflammation
83
Granuloma
Aggregate around cause of inflammation of epithelioid histocytes (tissue resident macrophages)
84
How does chronic inflammation lead to cancer?
Chronic inflammation> Metaplasia> Dysplasia> Carcinoma in situ> Invasive Carcinoma
85
Why does chronic inflammation cause cancer?
-Inflammation causes cellular changes and immune responses to repair damaged tissue → cell proliferation @ site of injury
-Inflammatory response becomes chronic → ↑ cell proliferation and ↑ risk of the development of mutations
-Chronic inflammatory cells (especially macrophages) generate high levels of reactive oxygen and nitrogen species to fight infection → release of mutagenic agents
-Inflammatory cells also release factors that interfere with regulation of cell replication exacerbating tumourgenesis
86
Conditions when chronic inflammation plays a key role
-Myocardial fibrosis (post MI)
-Atheroma development
-Multiple sclerosis (macrophages break down myelin)
87
Is osteoarthritis an inflammatory disease?
NO, inflammation plays a small role in disease pathogenesis. Primarily degenerative disease
88
Can basal cell carcinomas of the skin metastases?
No
89
Name of a malignant tumour of striated muscle
Rhabdo myo sarcoma
90
Is it common for liposarcomas to metastasise to bone?
No
91
Common bone metastases
Breast, lung, prostate, renal cell and thyroid cancer
92
Name of benign tumour of glandular epithelium
Adenoma
93
UK screening programs, types of cancer
Breast cancer, colorectal cancer and cervical cancer
94
Name of benign tumour of fat
Lipoma
95
Name of malignant tumour of glandular epithelium
Adenocarcinoma
96
Can ovarian cancer spread in the peritoneum
Yes, if it breaches the ovarian cavity
97
Why does leukemia cause a large range of symptoms?
WBC circulate round the body and so will any tumour of WBC, hence can spread easily causing many symptoms
98
Why do lymph nodes need to be removed when treating certain carcinomas?
Carcinomas can spread to the lymph nodes that drain the site of carcinomas so need to be removed to ensure as many tumours as possible have been taken out
99
Ways carcinomas can spread
-Invade nearby structures
-Through lymph nodes
-Through blood to bone
100
Steps for breast cancer treatment
1. Diagnosis breast cancer
2. Check has it spread to the axilla via lymph nodes, if yes axillary node need to be removed with breast cancer
3. Check has it spread to the rest of the body ie bone scan or CT scan, if yes systemic treatment needed (chemo)
4. If no to 3, Surgery need to remove breast cancer either with or without axillary clearance
5. Radiotherapy to remove any remaining micro metastases
6. Further adjuvant treatment depending on breast cancer pathology
101
Is a patient definitely cured if a tumour has been completely excised?
No, micro metastases could still be present
102
Adjuvant treatment
Extra treatment given after surgery
103
Tumour
Any abnormal swelling ie neoplasm, inflammation. Hypertrophy and hyperplasia
104
Neoplasm
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells with persists after the initiating stimulus has been removed
105
Lesion
area of abnormal tissue
106
Malignant-benign spectrum
Not always binary, some neoplasms are borderline so can present as benign or malignant but act as the opposite
107
Structure of neoplasms
Neoplastic cell (derived from nucleated cells) are supported by a stroma (a connective tissue framework which provides mechanical support and nutrition)
108
What does central necrosis of neoplasm show?
Neoplasm is growing so quickly that blood supply is unable to provide nutrients to the centre of the neoplasm
109
Tumour angiogenesis
Essential to growth, how a tumour forms a blood supply to provide its self with nutrients, tumour unable to grow via simple diffusion
110
Classification of neoplasms
Benign, borderline and malignant
111
Benign neoplasms
-Localised, non-invasive
-Slow growth rate
-Low mitotic activity
-Close resemblance to normal tissue
-Circumscribed or encapsulated, well defined
112
Histology of benign neoplasms
-Nuclear morphometry (shape) often normal
-Necrosis rare
-Ulceration rare
-Growth on mucosal surface usually exophytic (grow outward beyond the surface epithelium from which it originates)
113
Can benign neoplasms be harmful?
Yes, they can put pressure on adjacent structures, obstruct flow, produce hormones, transform to malignant neoplasm and anxiety for patient
114
Malignant neoplasms
-Invasive
-Metastases
-Rapid growth rate
-Variable resemblance to normal tissue
-Poorly defined or irregular border
115
Histology of malignant neoplasms
-Hyperchromatic (stain more deeply than normal) and pleomorphic (changes shape) nuclei
-Increased mitotic activity
-Necrosis and ulceration common
-Growth on mucosal surfaces and skin often endophytic (tending to grow inward into tissues in fingerlike projections from a superficial site of origin)
116
Why are malignant neoplasms harmful?
-destruction of adjacent tissue
-mets
-Blood loss from ulcers
-obstruct flow
-produce hormones
-paraneoplastic effects (disorders that occur when the immune system has a reaction to a cancerous tumour)
-anxiety and pain
117
Papilloma
Benign neoplasm of non-glandular non-secretory epithelium, prefix with cell type origin
118
Carcinoma
-Malignant epithelial neoplasm
-Prefix with epithelial cell type e.g. urothelial carcinoma
-Carcinomas of glandular epithelium are adenocarcinomas
119
Adenoma
-Benign neoplasm of glandular or secretory epithelium
-Prefix with cell type of origin, e.g. colonic adenoma, thyroid adenoma
120
Anaplastic neoplasm
Cell type of origin cannot be determined, typically poor prognosis
121
Teratoma
congenital (present prior to birth) tumor formed by different types of tissue. Teratomas in newborns are generally benign
122
Papilloma
Benign neoplasm of non-glandular non-secretory epithelium
123
How do decided a prefix for a neoplasm?
Depends on behavioural classification and cell type
124
Adenocarcinomas
Carcinomas of glandular epithelium
125
What is cell type origin of Lipoma?
adipocytes
126
What is cell type origin of Chondroma
cartilage
127
What is cell type origin of Osteoma
Bone
128
What is cell type origin of Angioma
Vascular
129
What is cell type origin of Rhabdomyoma
striated muscle
130
What is cell type origin of Leiomyoma
smooth muscle
131
What is cell type origin of Neuroma
nerves
132
What is cell type origin of Liposarcoma
adipose tissue
133
What is cell type origin of Rhabdomyosarcoma
striated muscle
134
What is cell type origin of Leiomyosarcoma
smooth muscle
135
What is cell type origin of Chrondrosarcoma
cartilage
136
What is cell type origin of Osteosarcoma
bone
137
What is cell type origin of Angiosarcoma
blood vessels
138
Carcinogenesis
The transformation of normal cells to neoplastic cells though permanent genetic alterations or mutations
Applies to malignant neoplasms
139
Carcinogenic vs Oncogenic
Both agents known or suspected to cause tumours
Carcinogenic = cancer causing
Oncogenic = tumour causing
140
Classes of carcinogens
Chemical, Viral, Ionising and non-ionising radiation, Hormones, parasites and mycotoxins, Miscellaneous
141
Host Factors
Ethnicity, Diet / Lifestyle, Constitutional factors (age, gender etc), Premalignant lesions, Transplacental exposure
142
conventional chemotherapy
* not selective for tumour cells
– except that they might be dividing faster
* usually hits normal cells which are dividing
– myelosuppression
– hair loss
– diarrhoea
143
What type of tumour is conventional chemotherapy most effective for treating
good for fast dividing tumours
– germ cell tumours of testis
– acute leukaemias
– lymphomas
– embryonal paediatric tumours
– choriocarcinoma
144
What type of tumour is conventional chemotherapy less effective for treating
not so good for slower dividing tumours
– most other tumours
145
targeted chemotherapy
exploits some difference between cancer cells
and normal cells to target drugs to the cancer
cells
– more effective
– less side effects
146
Methods for differentiating tumours
Gene arrays, proteomics, tissue microarrays
147
