Pathology Flashcards
Define inflammation
A reaction to injury or infection involving cells such as neutrophils and macrophages
How can inflammation be described as good or bad?
Good: in response to injury or infection
Bad: autoimmunity, over-reaction to stimulus
What is the difference between acute and chronic inflammation
Acute = sudden onset, short duration, usually resolves, lots of neutrophils
Chronic = slow onset or sequel to acute, long duration, may never resolve, lots of macrophages/lymphocytes
List 5 cells involved in inflammation
Neutrophils
Macrophages
Lymphocytes
Endothelial cells
Fibroblasts
How are neutrophils involved in inflammation?
These cells are first on scene, but short-lived and usually die at the scene
Their cytoplasmic granules of enzymes kill bacteria
They also release chemicals to attract other inflammatory cells (macrophages)
How are macrophages involved in inflammation?
These cells are long-lived, surviving for weeks-months
They have phagocytic properties, so ingest bacteria and debris
They may present the antigen to lymphocytes
How are lymphocytes involved in inflammation?
These are long lived cells which survive for years
They produce chemicals which attract other inflammatory cells
They contribute to the immunological memory to past infections/antigens
Specialised lymphocytes called plasma cells produce antibodies
How are endothelial cells involved in inflammation?
These cells become sticky (produce nitrous oxide) in areas or inflammation so inflammatory cells adhere
They become porous to allow inflammatory cells to pass into tissues (fluid leakage causes swelling)
They grow into areas of damage to form new capillary vessels
How are fibroblasts involved in inflammation?
These are long lived cells
They form collagen in areas of chronic inflammation and repair
Define granuloma
A pattern of chronic inflammation, consisting of a cluster of macrophages surrounded by lymphocytes, seen in Crohn’s disease and sarcoidosis
When and where does tissue regeneration occur?
When the initiating factor is removed, and where the tissue is undamaged and able to regenerate
Which cells are able to regenerate
Hepatocytes
Pneumocytes
Blood cells
Gut epithelium
Skin epithelium
Osteocytes
When and where does tissue repair occur?
When the initiating factor is still present, and where the tissue is damaged and unable to regenerate
Give examples of where repair takes place
Heart after myocardial infarction
Brain after cerebral infarction
Spinal cord after trauma
In repair, what is damaged tissue replaced by?
Fibrous tissue (collagen) from fibroblasts
In skin wounds, what is healing by 1st intentions?
When the edges of the wound are brought together by sutures
The wound will be bridged by fibrin, collagen forms, and the epithelium regenerates
There will be a smaller scar and faster healing
In skin wounds, what is healing by 2nd intention?
When the edges cannot be / are not brought together
The wound can’t be bridged by fibrin or collagen, so the wound heals from the bottom into the space, with the gap being restored by scar tissue
There will be a larger/more visible scar
Define thrombosis
A solid mass of blood constituents formed within an intact vascular system
Describe the process of thrombosis
- Normal blood flows consistently through the centre of the vessel in laminar flow
- Exposed collagen from endothelium damage causes platelets to stick to the side of the vessel (because nitrous oxide production is stopped)
- Platelets release activating factor which attracts others (positive feedback)
- The blood flow becomes more turbulent and red blood cells also become trapped
- A thrombus forms due to the presence of clotting precursors and fibrin deposition
What are the three causes of thrombosis?
Change in blood flow (laminar -> turbulent)
Change in vessel wall (endothelial damage e.g. from smoking, diabetes etc.)
Change in blood constituents (e.g. abnormal clotting factors)
What is stasis?
A cause of thrombosis in veins due to the blood flow being slower
How is thrombosis prevented?
Low-dose aspirin (inhibits platelet aggregation by irreversibly inhibiting platelet cyclo-oxygenase, no positive feedback loop)
Define embolus
A mass of material in the vascular system which is able to become lodged within a vessel and block it
Give some examples of emboli
Deep vein thrombosis breaks off and becomes lodged in the smaller vessels of the lungs, causing pulmonary embolism
Endocarditis causes material to break off and cause septic emboli, which can become lodged in the liver or lungs
IV drug users are injected emboli into their blood vessels
Define ischemia
A reduction in blood flow
When/where does ischemia occur?
Most commonly in cells which are further away from the vessel, so are receiving less oxygen
The cells are still alive, but poorly/not functioning
Define infarct
A reduction of blood flow (ischemia) with subsequent cell death
When/where does infarction happen?
Occurs in organs with only one blood supply (end artery supply)
A thrombus/embolus blocks off the entire supply to the organ, leading to infarct/death
What are the 5 cardinal signs of inflammation
Redness
Swelling
Heat
Pian
Loss of function
Describe the time course of atherosclerosis and the change in structure
Increases with age (steep increase at 40/50)
- fatty streaks present at younger ages (early stages, mainly inflammatory cells)
- then intermediate lesions (involvement of muscle cells, T lymphocytes, platelets)
- established atherosclerosis at older ages (fibrous plaques/advanced lesions, covered by fibrous cap, prone to rupture)
- plaque rupture (balance shifts in favour of inflammation, cap becomes weak, leads to thrombus and vessel occlusion
Describe the distribution of atherosclerosis
Only in high pressure arteries
- found within peripheral and coronary arteries
- common in aorta
- changes in flow/turbulence (e.g. bifurcations) cause artery to alter endothelial cell function and wall thickness (neointima)
- never in low pressure systems like pulmonary arteries
List the constituents of an atherosclerotic plaque
Fibrous tissue (forms the cap)
Lipid deposits
Cholesterol
T lymphocytes
Macrophages
List some risk factors for atherosclerosis
Modifiable…
Smoking
Weight (obesity)
Lack of exercise
Diet (high serum cholesterol)
Non-modifiable…
Age
Gender
Ethnicity
Family history
Genetic causes of increased weight/hyperlipidaemia/diabetes
List some complications of atherosclerosis
Cerebral infarction
Myocardial infarction, cardiac failure
Carotid atheroma (emboli causes TIA/stroke)
Aortic aneurysm (rupture -> sudden death)
Peripheral vascular disease
Describe the process of atherosclerosis
- The smooth endothelial lining of a blood vessel becomes damaged (dysfunction)
- The damage allows low-density lipids (LDLs) to enter the intima layer, where they become oxidised and cannot leave
- An inflammatory response is caused by macrophages engulfing cholesterol after it is oxidised, to form foam cells
- These promote smooth muscle cell proliferation in the intima and migration to form the fibrous cap
How is endothelial damage caused?
Smoking - free radicals, nicotine, and carbon monoxide
Hypertension - sheering forces (often at bifurcations)
Diabetes - superoxide anions and glycosylation products cause oxidative stress and epithelial injury
Hyperlipidaemia - produces superoxide free radicals and increase nitrous oxide deactivation
Define apoptosis
Programmed cell death
How does apoptosis occur?
Nuclear condensing and cell shrinkage
Nuclear fragmentation and phagocytes engulfing the nuclear bodies
Which gene checks for DNA damage, and what is it checking for?
p53 gene…
Single-strand breaks
Doble-strand breaks
Base alteration
Cross-linkage
When can apoptosis be useful?
During development
Removing old/non-functioning cells
Give two examples of when apoptosis occurs in disease
Cancer - lack of apoptosis leading to tumours
HIV - too much apoptosis killing T lymphocytes
Define necrosis
Traumatic cell death
Give some clinical examples of necrosis
Cerebral infarction
Frostbite
Avascular necrosis of bone
Pancreatitis
Toxic spider venom
Gangrene
Describe coagulative, liquefactive, and caseous necrosis
Coagulative… appears solid-like, usually caused by infarction (except in brain)
Liquefactive… appears liquid-like, associated with parasitic infection
Caseous… appears like soft cheese, occurs when immune system can’t remove noxious stimuli (e.g. TB)
Define hypertrophy
Increase in the size of a tissue caused by an increase in the size of the constituent cells
Give an example of where/when hypertrophy occurs
Occurs in cells which can’t divide (cardiac/skeletal muscle)
e.g. weight training -> muscle hypertrophy
e.g. hypertrophic cardiomyopathy
Define hyperplasia
Increase in the size of the tissue caused by an increase in the number of constituent cells
Give an example of where/when hyperplasia occurs
Occurs in cells which can divide
e.g. benign prostatic hyperplasia
Define atrophy
Decrease in the size of a tissue caused by a decrease in number of the constituent cells or decrease in their size
Give an example of where/when atrophy occurs
Dementia - loss of neurons, brain gets smaller
Immobilisation - causes muscle atrophy
Optic atrophy - optic nerve gets smaller
Define metaplasia
Change in differentiation of a cell from one fully-differentiated type to another
Give an example of metaplasia
Smoking causes ciliated epithelium to change to squamous epithelium in the bronchi, the lack of cilia causes ‘smokers cough’
Define dysplasia and give examples
An imprecise term for the morphological changes seen in the progression to becoming cancer
e.g. abnormal architecture/arrangement of cells leading to carcinoma formation
Also refers to development abnormality
e.g. hip dysplasia
Define tumour
Any abnormal growth
- including neoplasm, inflammation, hypertrophy, hyperplasia
Define neoplasm
A lesion resulting from the autonomous and abnormal growth of cells which persists after the initiating stimulus is removed
Describe the origin and structure of neoplastic cells
Derived from nucleated cells and are initially monoclonal, with a growth pattern and synthetic activity related to the parent cell
What is the stroma of a neoplasm?
A ‘mattress’ of connective tissue framework, rich in fibroblasts, providing nutrition and mechanical support
What is tumour angiogenesis and why is it important?
Proliferation of blood vessels to supply a tumour with oxygen and nutrients
- the presence of blood vessels determines the neoplasm growth
What happens if a malignant tumour grows too fast for the angiogenesis to keep up
They will have central necrosis
What are the two behavioural classifications of tumours
Benign
Malignant
How are benign and malignant tumours different?
(invasiveness, metastases, ulceration/necrosis, growth rate, growth pattern, nucleus, resemblance to normal tissue, border)
Invasiveness… B = non-invasive, M = invasive
Metastases… B = none, M = potential
Ulceration/necrosis… B = rare, M = common
Growth rate… B = slow, M = fast
Growth pattern… B = exophytic (up/out), M = endophytic (down/in)
Nucleus… B = normal, M = hyperchromatic, pleomorphic
Resemblance to normal tissue… B = close, M = variable
Border… B = circumscribed/encapsulated, M = poorly defined/irregular border
Why are benign and malignant tumours treated?
- Benign tumours put pressure on adjacent structures, obstruct blood flow, produce hormones, cause anxiety, and can transform into malignancies
- Malignant tumours destruct adjacent tissues, they metastasise and cause paraneoplastic effects, cause blood loss from ulcers, obstruct blood flow, produce hormones, and cause pain and anxiety
What are benign epithelial neoplasms called?
Of glandular/secretary epithelium = adenoma (e.g. thyroid adenoma)
Of non-glandular/non-secretary epithelium = papilloma (squamous cell papilloma)
What are benign connective tissues neoplasms called?
Of adipocytes = lipoma
Of cartilage = chondroma
Of bone = osteoma
Of blood vessels = angioma
Of fibroblasts = fibroma
Of nerves = neuroma
Of striated muscle = rhabdomyoma
Of smooth muscle = leiomyoma
What are malignant epithelial neoplasms called?
Carcinoma (e.g. urothelial carcinoma)
- of glandular epithelium = adenocarcinoma
What are malignant connective tissue neoplasms called?
Of adipocytes = liposarcoma
Of cartilage = chondrosarcoma
Of bone = osteosarcoma
Of blood vessels = angiosarcoma
Of fibroblasts = fibrosarcoma
Of striated muscle = rhabdomyosarcoma
Of smooth muscle = leiomyosarcoma
What is an anaplastic tumour?
A tumour with an unknown cell-type of origin
In the histological classification, how are neoplasms named?
All neoplasms have the suffix ‘-oma’
The prefix is determine by the behavioural classification and the cell-type of origin
What are the exceptions to the naming of neoplasms?
Not all ‘-omas’ are neoplasms (e.g. granuloma)
Not all malignant tumours are carcinoma/sarcoma (e.g. lymphoma, melanoma)
Some tumours are eponymously named (e.g. Kaposi’s sarcoma = angiosarcoma)
Using two examples, how can cancers be treated by knowing about there pathology?
Basal cell carcinomas… only invade locally, never spread to other parts of the body, so can be cured by complete local excision
Leukaemia… cancerous white blood cells will circulate around the whole body, cancer can temporarily be in all organs, so can’t be excised, needs to be treated with systemic chemotherapy
What is adjuvant therapy (in cancer treatment)?
Extra treatment that is given after surgical excision, to treat micro-metastases that couldn’t be removed
e.g. radiotherapy, anti-oestrogen therapy (only for oestrogen-receptor positive cells)
Define carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
What is a carinogen
An agent which is know or suspected to cause tumours by acting on DNA (are mutagenic)
What are the 5 classes of carcinogens?
Chemical
Viral
Radiant energy
Biological
Miscellaneous
Describe the features of chemical carcinogens and give some examples
No common structural feature
Some act directly but most need metabolic conversion by enzymes
e.g. polycyclic aromatic hydrocarbons (in smoking/mineral oils) -> lung and skin cancer
e.g. aromatic amines (in rubber/dye industries) -> bladder cancer
Describe the features of viral carcinogens and give some examples
These cause 10-15% of all cancers, but most oncogenic viral infections don’t result in cancer
e.g. Epstein Barr Virus (glandular fever) -> nasopharyngeal carcinoma
e.g. Human papillomavirus (HPV) -> squamous cell carcinoma of cervix/penis/anus/oropharynx
e.g. Hepatitis B (DNA) or C (RNA) -> hepatocellular carcinoma
Describe the features of radiant carcinogens and give some examples
Can be ionising (e.g. excessive X-rays, nuclear explosion) or non-ionising (e.g. UV A/B light)
List the different kinds of biological carcinogens
Hormones… oestrogen (increased risk or mammary/endothelial cancers), anabolic steroids (increased risk of hepatocellular carcinoma)
Mycotoxins… aflatoxin B from Aspergillus fungi (causes hepatocellular carcinoma)
Parasites… Schistosoma worm (causes bladder cancer)
List some factors which affect the likelihood of cancer
- Ethnicity… decreased skin cancer in darker skin (more melanin), cultural practices (e.g. reverse smoking)
- Constitutional… age (increased exposure to carcinogens), gender (breast cancer more common in women), inherited predisposition
- Diet/lifestyle… excessive alcohol (increased risk of liver, colon cancer etc.), obesity (increased risk of breast, colon, kidney cancer), unprotected sex (increased risk of HPV-related cancers), exercise (reduces risk of colon and breast cancer)
- Premalignant conditions… local abnormalities with increased risk of malignancy (colonic polyps, cervical dysplasia, ulcerative colitis, undescended testes)
Describe the development of a carcinoma in situ
One cell mutates, then replaces adjacent healthy cells (because of excessive growth or lack of apoptosis)
The cancerous cells will fill in the space (e.g. lumen of a duct) but not pass through the basement membrane
This means they can be treated by excision (no access to lymphatics/blood vessels so can’t spread)
What is an invasive carcinoma?
A carcinoma which has broken through the basement membrane and is likely to spread through lymphatics/blood vessels
This means it cannot be treated by excision alone and needs systemic chemotherapy
Describe the process of metastasis
- Tumour grows - replacing healthy cells
- Invade basement membrane - using enzymes which break down collagen and other proteins, and using tumour cell derived motility factors
- Invade extracellular matrix - enzymes and cell motility
- Intravasation (enter lymphatic/blood vessel) - enzymes and cell motility
- Evasion of host immune defence - aggregation with platelets, shedding of surface antigens, adhesion to other tumour cells (protects cells in middle)
- Extravasation (exit lymphatic/blood vessel) - using adhesion receptors, enzymes and cell motility
- Invade extracellular matrix - enzymes and cell motility
- Grow at metastatic site - using growth factors
- Angiogenesis (grow its own blood supply) - promoted by vascular endothelial and basic fibroblast growth factors
Name some common sites of metastases
Lung - many common cancers, tumours travel through the venous system and become lodged in the smaller capillaries of the lung
Liver - tumours of the colon, stomach, pancreas, and intestine, drain through the portal vein and become lodged in the smaller capillaries of the liver
Bone - prostate, breast, thyroid, lung, and kidney cancers commonly metastasise in the bone and can promote excessive bone growth or loss
How does conventional chemotherapy work?
It works by stopping DNA replication…
- by cross-linking strands so they can’t be split
- by binding to the mitotic spindle so they can’t divide
It is non selective to tumour cells, so acts on any cell which divides quickly, causing myelosuppression, hair loss, diarrhoea
It is good for fast growing cancers (e.g. leukaemia) but not slower growing ones (e.g. breast, prostate, colorectal cancers)
How does targeted chemotherapy work?
It exploits the differences between cancer cells and normal cells to target the drugs to cancer cells only
- e.g. monoclonal antibody targeting growth factor-A receptor
- e.g. a small molecular inhibitor of growth factor-A receptor
These are more effective and give less side effects
