ICS - Pathology 2 Flashcards
Define inflammation
A local physiological response to tissue injury
Give an advantage of inflammation
Can destroy invading micro-organisms and can prevent the spread of infection
Give a disadvantage of inflammation
Can produce disease and lead to distorted tissues with permanently altered function
Define acute inflammation
Initial and often transient series of tissue reactions to injury
What are the main cells involved in acute inflammation?
Neutrophils and monocytes
What are the main steps of acute inflammation?
- Initial reaction of tissue to injury- Vascular component (vessels dilate)- Exudative component (vascular leakage of protein-rich fluid)- Neutrophil polymorph (phagocytose)
Define exudate
A protein-rich fluid that leaks out of vessel walls due to increased vascular permeability
What are examples of acute inflammation?
- Acute appendicitis- Frostbite - Streptococcal sore throat
What vascular changes occur in acute inflammation?
- Increased blood flow through capillaries- Increased vascular permeability (exudation)
What is the role of tissue macrophages in acute inflammation?
Secrete chemical mediators that attract neutrophil polymorphs
What is the role of the lymphatic system in acute inflammation?
Lymphatic channels dilate and drain away oedematous fluid (reduces swelling). Antigens are also carried to lymph nodes for recognition by lymphocytes
What are the main steps of neutrophil polymorph migration?
- Margination 2. Adhesion/Pavementing3. Emigration4. Diapedesis
Describe margination (neutrophil polymorph migration)
Neutrophils migrate to the peripheral part of blood vessels near the endothelium due to increased plasma viscosity
Describe adhesion/pavementing (neutrophil polymorph migration)
Neutrophils adhere to vascular endothelium in venules. Results from interactions between paired adhesion molecules (on leucocyte and endothelial surfaces)
Describe emigration (neutrophil polymorph migration)
Neutrophils pass through endothelial cells and through the basal lamina into the adventitia
Describe diapedesis (neutrophil polymorph migration)
A passive process that depends on hydrostatic pressure. RBCs sometimes escape from vessels which indicates severe vascular injury (e.g. tear in vessel wall)
What is released from injured tissues that causes the acute inflammation response to spread?
Chemical mediators e.g. histamine and thrombin
Give 3 endogenous chemical mediators of acute inflammation
- Bradykinin2. Histamine3. Nitric oxide
What is the main source (and other sources) of histamine?
Mast cells (stored in granules in their cytoplasm)Also basophils, eosinophils and platelets
What do chemical mediators such as histamine cause?
- Vasodilation- Emigration of neutrophils- Chemotaxis- Increased vascular permeability- Itching and pain
Give 6 causes of inflammation
- Microbial infections (bacteria, viruses)2. Hypersensitivity reactions (parasites, TB)3. Physical agents (trauma, burns, frost bite)4. Chemicals (corrosives, acids, alkalis)5. Bacteria toxins6. Tissue necrosis (ischaemia, infarction)
What does viral infection result in?
Cell death due to intracellular multiplication
What does bacterial infection result in?
The release of exotoxins (involved in the initiation of inflammation) or endotoxins
What are the 5 cardinal signs of inflammation?
- Rubor (redness)2. Calor (heat)3. Tumor (swelling)4. Dolor (pain)5. Loss of function
What are the 4 outcomes of inflammation?
- Resolution2. Suppuration3. Organisation4. Progression
Describe resolution in inflammation
- Complete restoration of tissues to normal- Minimal cell death and tissue damage- Rapid destruction of causal agent- Most common in organs capable of regeneration (e.g. liver)- E.g. acute lobar pneumonia
Describe suppuration in inflammation
- Formation of pus- Pus accumulates and becomes surrounded by pyogenic membrane- Leads to granulation tissue and scarring- E.g. staphylococcus aureus
Describe organisation in inflammation
- Replacement by granulation tissue (scar tissue formation)- Occurs when substantial volumes of tissue become necrotic or is not easily digested- Fibrosis occurs- E.g. pleural space following acute lobar pneumonia
Describe progression in inflammation
- Causative agent is not removed - Progresses to chronic inflammation
How can acute inflammation be diagnosed histologically?
Looking for the presence of neutrophil polymorphs
Give 4 systemic effects of acute inflammation
- Fever2. Feeling unwell3. Weight loss4. Reactive hyperplasia of the reticuloendothelial system
Define chronic inflammation
Subsequent prolonged response to tissue injury
What are the main cells involved in chronic inflammation?
Lymphocytes, macrophages and plasma cells
Give 4 causes of chronic inflammation
- Primary chronic inflammation- Transplant rejection- Recurrent acute inflammation- Progression from acute inflammation
Give 5 examples of primary chronic inflammation
- Resistance of infective agent (e.g. TB, leprosy)2. Endogenous materials (e.g. necrotic tissue, uric acid crystals)3. Exogenous materials (e.g. silica, asbestos)4. Autoimmune conditions (e.g. rheumatoid arthritis, chronic gastritis)5. Primary granulomatous diseases (e.g. Crohn’s, sarcoidosis)
Give 4 macroscopic appearances of chronic inflamamtion
- Chronic ulcer- Chronic abscess cavity- Granulomatous inflammation- Fibrosis
Give 4 microscopic appearances of chronic inflammation
- Lymphocytes, plasma cells and macrophages2. Exudation not common3. Evidence of continuing destruction4. Possible tissue necrosis
Define granulation tissue
Tissue composed of small blood vessels in a connective tissue matrix with myofibroblasts (important in healing and repair)
Define granuloma
Aggregate of epithelioid histocytes
Give examples of granulomatous diseases
- TB- Leprosy- Crohn’s disease- Sarcoidosis
Explain the difference between resolution and repair
Resolution - initiating factor is removed and tissue is able to regenerateRepair - initiating factor is still present and tissue is unable to regenerate
Name 5 cells capable of regeneration
- Hepatocytes2. Osteocytes3. Pneumocytes4. Blood cells5. Gut and skin epithelial cells
Name 2 cells incapable of regeneration
- Myocardial cells2. Neuronal cells
What cells produce collagen in fibrous scarring?
Fibroblasts
Give an example of a chronic inflammatory process from the start
Infectious mononucleosis
Define laminar flow
Streamline movement of blood - cells travel in the centre of arterial vessels and don’t touch the sides
Define thrombosis
Solidification of blood contents that forms within vascular system during life
Give 2 reasons why thrombosis is uncommon
- Laminar flow2. Non sticky endothelial cells
What do platelets contain?
- Alpha granules (involved in platelet adhesion e.g. fibrinogen)2. Dense granules (involved in platelet aggregation e.g. ADP)
What is Virchow’s traid?
3 factors that can lead to thrombus formation:1. Reduced blood flow2. Blood vessel injury3. Increased coaguability
What are the 4 outcomes of thrombosis?
- Resolution (body dissolves and clears it)2. Organisation (becomes a scar and slightly narrows vessel lumen)3. Recanalisation (intimal cells may proliferate and capillaries may grow into thrombus and fuse)4. Embolus (fragments break off into circulation)
Describe an arterial thrombus
- Commonly caused by atheroma- High pressure- Mainly made of platelets- Can lead to myocardial infarction/stroke- Treated by anti-platelets e.g. aspirin
Describe a venous thrombus
- Commonly caused by stasis- Low pressure- Mainly made of RBCs- Can lead to deep vein thrombosis/pulmonary embolism- Treated by anti-coagulants e.g. warfarin, apixaban
Define embolus
Mass of material (usually a thrombus) in the vascular system able to lodge in a vessel and block its lumen
Give 6 causes of embolisms
- Thrombus2. Air (e.g. pressurised systems of IV fluids)3. Cholesterol crystals (from atheromatous plaques)4. Tumour5. Amniotic fluid6. Fat (severe trauma with multiple fractures)
Describe arterial embolisms
- Systemic embolism- Can travel anywhere downstream of entry point- Cholesterol crystals from atheromatous plaques in the descending aorta can go to any lower limb or renal artery
What are mural thrombi?
Thrombi that attach to the wall of blood vessels and cardiac chambers. Mural thrombi in the left ventricle can go anywhere in the systemic circulation
Describe venous embolisms
- Pulmonary embolism- Emboli travel to the vena cava and lodge in the pulmonary arteries- The lungs acts as a filter for venous emboli (blood vessels split down to capillary size)
Define ischaemia
Reduction in blood flow
Define infarction
Necrosis of part of an organ that occurs when the artery supplying it becomes obstructed
Give 3 examples of organs with a dual arterial supply
- Liver (hepatic arteries and portal veins)- Lungs (bronchial arteries and pulmonary veins)- Some areas of the brain around the circle of willis
Why are tissues with an end arterial supply more susceptible to infarction?
Only have a single arterial supply
What is a reperfusion injury?
Damage to tissue during reoxygenation due to the release of waste products
Give a drug that is used to prevent thrombosis
Aspirin (inhibits platelet aggregation)
What are the main steps of coagulation?
- Vascular spasm- Primary platelet plug (adhesion, activation, aggregation)- Secondary stable plug
Define atherosclerosis
Disease characterised by the formation of atherosclerotic plaques in the intima of vessel walls
Where is atherosclerosis more common and why?
Systemic circulation as it is a higher pressure system
What are the 3 main constituents of an atheromatous plaque?
- Lipids2. Fibrous tissue3. Lymphocytes
Briefly describe the formation of an atheromatous plaque
- Damage to endothelial cells - secrete chemoattractants- LDL in the blood will accumulate in the arterial wall- Macrophages attracted to site and take up lipids to form foam cells- Foam cells accumulate in the intima to form a fatty streak- Foam cells rupture to release lipids, cytokines and growth factors- Smooth muscle cells proliferate and migrate from the media to the intima- Dense fibrous cap (collagen) forms around the lipid core
Give 7 risk factors for atherosclerosis
- Hypercholesterolaemia2. Smoking3. Hypertension4. Hyperlipidaemia5. Uncontrolled diabetes mellitus6. Male sex7. Increasing age
Give 5 preventative measures for atherosclerosis
- Smoking cessation- Blood pressure control- Weight reduction- Taking low dose aspirin regularly- Statins
How does smoking increase the risk of atherosclerosis?
Cigarette smoke releases free radicals, nicotine and carbon monoxide into the body which all damage endothelial cells
How does hypertension increase the risk of atherosclerosis?
Greater force exerted on endothelial cells and so more likely to cause damage
Define apoptosis
Programmed cell death of a single cell without harm to surrounding cells
Why is apoptosis good?
- Removal of cells during development- Removal of cells during normal turnover (e.g. cells in intestinal villi at tips replaced by cells from below)
What is the role of the p53 protein?
Looks for DNA damage and if detected, triggers apoptosis
Give 4 inhibitors of apoptosis
- Growth factors- Extracellular cell matrix- Sex steroids- Some viral proteins
Give 8 inducers of apoptosis
- Growth factor withdrawal2. Loss of matrix attachment3. Glucocorticoids4. Some viruses5. Free radicals6. Ionising radiation7. DNA damage8. Ligand binding at ‘death receptors’
Apoptosis can be turned on by a family of protease enzymes called …
Caspases
Caspases can be activated by the activation of …
FAS receptor
Describe the intrinsic pathway of apoptosis
- Uses pro- and anti-apoptotic members of the Bcl-2 family (Bax and Bcl-2)- Ratio determines cell’s susceptibility to apoptotic stimuli
What do Bcl-2 and Bax do?
- Bcl-2 inhibits apoptosis- Bax enhances apoptosis
Describe the extrinsic pathway of apoptosis
- Ligand-binding at death receptors on the cell surface- This promotes clustering on the cell surface and initiates cascade- Caspases are activated and apoptosis is triggered
Give an example of a disease where there is a lack of apoptosis
Cancer. Mutations in p53 gene so p53 protein cannot detect DNA damage. Results in increasing tumour size and accumulation of genetic mutations
Give an example of a disease where there is too much apoptosis
HIV. Apoptosis induced in CD4 helper cells which reduces their numbers and produces an immunodeficient state
Define necrosis
Traumatic cell death of a large number of cells
Give 3 examples of events that can lead to necrosis
- Frost bite- Avascular necrosis- Infarction
Name the 4 types of necrosis
- Coagulative (caused by ischaemia)2. Liquefactive (lack of substantial supporting stroma in brain)3. Caseous (‘cheese’ pattern)4. Gangrene (necrosis with rotting of tissue)
Define hypertrophy
Increase in the size of a tissue due to an increase in the size of its constituent cells
Define hyperplasia
Increase in the size of a tissue due to an increase in the number of its constituent cells
Define atrophy
Decrease in the size of a tissue due to a decrease in the size or number of its constituent cells
Define metaplasia
Change in cell differentiation from one fully-differentiated cell type to another fully-differentiated cell type
Give an example of a disease that demonstrates metaplasia
Barrett’s oesophagus - continued acid reflux causes the cells at the lower end of the oesophagus to change from stratified squamous cells to columnar
Describe metaplasia in smoking
Bronchial epithelium changes from ciliated columnar to squamous when exposed to cigarette smoke continuously
Define dysplasia
Morphological changes that may be seen in cells in the progression to becoming cancer
Define neoplasia
Uncontrolled, abnormal growth of cells or tissues (cancer)
What is a neoplasm composed of?
Neoplastic cells and stroma
Define carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
Define carcinogenic, oncogenic and mutagenic
Carcinogenic - cancer causing (malignant only)Oncogenic - neoplasm causing (both benign and malignant)Mutagenic - acts on DNA
What percentage of cancer risk is environmental?
85% environmental and 15% genetic
Give 5 host factors that can affect cancer risk
- Ethnicity2. Diet/lifestyle (diet/exercise/sexual behaviour)3. Constitutional factors (age/gender/inherited predisposition)4. Premalignant conditions5. Transplacental exposure
Give an example of transplacental exposure causing an increased cancer risk
Diethylstilbestrol associated with increased risk of vaginal cancer
Give the 5 classes of carcinogens
- Chemical2. Viral3. Ionising and non-ionising radiation4. Hormones, parasites and mycotoxins5. Miscellaneous
Define carcinogen
Environmental agents known or suspected to cause neoplasms
Describe chemical carcinogens
Most require metabolic conversion from pro-carcinogens to ultimate carcinogens
Give 4 examples of chemical carcinogens
- Polycyclic aromatic hydrocarbons cause lung/skin cancer (cigarettes/mineral oils)- Aromatic amines cause bladder cancer (rubber/dyes)- Nitrosamines cause gut cancer- Alkylating agents cause leukaemia - small risk in humans (found in chemotherapeutic agents)
What causes skin cancer?
Exposure to UV light
Give 2 examples of miscellaneous carcinogens
Asbestos and metals
How are neoplasms classified?
Behavioural and histogenetic classifications
Describe the behavioural classification of neoplasms
Can be classified as benign, malignant or borderline
Describe the histogenetic classification of neoplasms
Classified based on the specific cell of origin of the tumour (if origin is unknown, it is anaplastic)
Give 7 features of benign neoplasms
- Non-invasive2. Localised3. Exophytic (grows outwards)4. Low mitotic activity5. Necrosis and ulceration are rare6. Normal nuclei7. Close resemblance to normal tissue
Give 7 features of malignant neoplasms
- Invasive2. Metastases3. Endophytic (grows inwards)4. High mitotic activity5. Necrosis and ulceration are common6. Poorly defined border7. Poor resemblance to normal tissue
Give 4 consequences of benign neoplasms
- Pressure on adjacent structures2. Obstruction to flow3. Transformation into malignant neoplasms4. Anxiety
Give 4 consequences of malignant neoplasms
- Destroy surrounding tissue2. Blood loss due to ulceration3. Pain4. Anxiety
What is a papilloma?
Benign tumour of non-glandular epithelium
What is an adenoma?
Benign tumour of glandular epithelium
What is a carcinoma?
Malignant epithelial tumour
What is an adenocarcinoma?
Malignant tumour of glandular epithelium
What is a lipoma?
Benign tumour of adipocytes
What is a rhabdomyoma?
Benign tumour of striated muscle
What is a leiomyoma?
Benign tumour of smooth muscle
What is a chondroma?
Benign tumour of cartilage
What is an osteoma?
Benign tumour of bone
What is a sarcoma?
Malignant tumour of connective tissue
What is a liposarcoma?
Malignant tumour of adipocytes
What is a neuroma?
Benign tumour of nerves
What is a rhabomyosarcoma?
Malignant tumour of striated muscle
What is a leiomyosarcoma?
Malignant tumour of smooth muscle
What is a chondrosarcoma?
Malignant tumour of cartilage
What is an osteosarcoma?
Malignant tumour of bone
What is a melanoma?
Malignant tumour of melanocytes
What is a lymphoma?
Malignant tumour of lymphoid cells
What is a mesothelioma?
Malignant tumour of mesothelial cells (pleura)
Define metastasis
The process whereby malignant tumours spread from their site of origin to form other tumours at distant sites
What never metastasises?
Basal cell carcinomas
What are the 7 steps of metastasis?
- Detachment2. Invasion3. Intravasation4. Evasion5. Adherence6. Extravasation7. Proliferation
What is required for invasion (tumour metastasis)?
Proteases and cell motility
What is required for intravasation (tumour metastasis)?
Collagenases and cell motility
What is required for extravasation (tumour metastasis)?
Adhesion receptors, collagenases and cell motility
Give 3 tumour evasion methods
- Aggregation with platelets2. Shedding of surface antigens3. Adhesion to other tumour cells
Which 5 carcinomas most commonly spread to bone?
PB KTL1. Prostate2. Breast3. Kidneys 4. Thyroid5. Lungs
Carcinomas that commonly spread to the axillary lymph nodes are …
Breast carcinomas
Which route of metastasis do carcinomas prefer?
Lymphatic spread
Which route of metastasis do sarcomas prefer?
Haematogenous spread (often spread to lung via vena cava –> heart –> pulmonary arteries)
Which tumours commonly metastasise to the liver?
- Colon- Stomach- Pancreas- Carcinoid(via portal vein)
Describe tumour staging
T - primary tumour (size)N - lymph node status (degree of lymph node involvement)M - metastatic status (extent of distant metastases)
How would you cure a basal cell carcinoma and why?
Complete local excision as they do not metastasise
How would you treat leukaemia and why?
Chemotherapy as it is systemic and so circulates all around the body
Why is adjuvant therapy often used?
Micrometastases may form
Give an advantage of chemotherapy
Works well against fast dividing tumours e.g. lymphomas
Give a disadvantage of chemotherapy
Non selective for tumour cells, normal cells are affected
What is targeted chemotherapy most effective against?
Slower dividing tumours e.g. lung, colon and breast
What is targeted chemotherapy?
Cancer cells and normal cells can be differentiated
What kind of drugs can be used in targeted chemotherapy?
Monoclonal antibodies and small molecular inhibitors
