Introductory Clinical Sciences Flashcards
Define inflammation.
A local physiological response to tissue injury.
Give a benefit of inflammation.
Inflammation can destroy invading micro-organisms and can prevent the spread of infection.
Give a disadvantage of inflammation.
Inflammation can produce disease and can lead to distorted tissues with permanently altered function.
Define exudate.
A protein rich fluid that leaks out of vessel walls due to increased vascular permeability.
What are the 4 outcomes of inflammation?
- Resolution.
- Suppuration.
- Organisation (scar tissue formation).
- Progression onto chronic inflammation.
Give 6 causes of acute inflammation.
- Microbial infections (bacteria and viruses).
- Chemicals (corrosives, acids/alkalis).
- Physical agents (trauma, burns, frost bite).
- Hypersensitivity reactions (TB).
- Bacterial toxins.
- Tissue necrosis.
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.
Give 5 cardinal signs of inflammation.
- Redness (rubor).
- Swelling (tumor).
- Pain (dolor).
- Heat (calor).
- Loss of function.
How can acute inflammation be diagnosed histologically?
By looking for the presence of neutrophil polymorphs.
Give 3 endogenous chemical mediators of acute inflammation.
- Bradykinin.
- Histamine.
- Nitric Oxide.
What are 4 systemic effects of acute inflammation?
- Fever.
- Feeling unwell.
- Weight loss.
- Reactive hyperplasia of the reticuloendothelial system.
What cells are involved in chronic inflammation?
Macrophages and plasma cells (B and T lymphocytes).
What cell can form when several macrophages try to ingest the same particle?
Multinucleate giant cell.
Give 4 causes of chronic inflammation.
- Primary chronic inflammation.
- Transplant rejection.
- Recurrent acute inflammation.
- Progression from acute inflammation.
Give examples of primary chronic inflammation.
- Infective substances having resistance to phagocytosis e.g. TB, leprosy.
- Endogenous materials e.g. uric acid crystals.
- Exogenous materials e.g. asbestos.
- Autoimmune diseases e.g. chronic gastritis, rheumatoid arthritis etc.
- Other chronic inflammatory diseases e.g. chronic inflammatory bowel disease.
In which type of inflammation would you see neutrophil polymorphs?
Acute inflammation.
What are some macroscopic features of chronic inflammation?
- Chronic ulcer.
- Chronic abscess cavity.
- Granulomatous inflammation.
- Fibrosis.
What is granulation tissue?
Granulation tissue is composed of small blood vessels in a connective tissue matrix with myofibroblasts. It is important in healing and repair.
Define granuloma.
An aggregate of epithelioid histocytes.
Give an example of a granulomatous disease.
TB, leprosy, Crohn’s disease and sarcoidosis.
The activity of what enzyme in the blood can act as a marker for granulomatous disease?
Angiotensin converting enzyme.
What kind of disease is TB?
A granulomatous disease.
What is the difference between resolution and repair?
Resolution is when the initiating factor is removed and the tissue is able to regenerate. In repair, the initiating factor is still present and the tissue is unable to regenerate.
Name 5 types of cells capable of regeneration.
- Hepatocytes.
- Osteocytes.
- Pneumocytes.
- Blood cells.
- Gut and skin epithelial cells.
Name 2 types of cells that are incapable of regeneration.
- Myocardial cells.
- Neuronal cells.
Define abscess.
Acute inflammation with a fibrotic wall.
Define thrombosis.
Formation of a solid mass from blood constituents in an intact vessel in the living.
Give 2 reasons why thrombosis formation is uncommon.
- Laminar flow.
- Non sticky endothelial cells.
What are the 3 factors that can lead to thrombosis formation?
- Change in vessel wall.
- Change in blood constituents.
- Change in blood flow.
Define embolus.
A mass of material (often a thrombus) in the vascular system that is able to become lodged in a vessel and block it.
Define ischaemia.
Decreased blood flow.
Define infarction.
Decreased blood flow with subsequent cell death.
Why are tissues with an end arterial supply more susceptible to infarction?
They only have a single arterial supply and so if this vessel is interrupted infarction is likely.
Give 3 examples of organs with a dual arterial supply.
- Lungs (bronchial arteries and pulmonary veins).
- Liver (hepatic arteries and portal veins).
- Some areas of the brain around the circle of willis.
What can happen if ischaemia is rectified?
Re-perfusion injury can occur due to the release of waste products.
What are the consequences of an arterial embolus?
An arterial embolus can go anywhere! The consequences could be stroke, MI, gangrene etc.
What are the consequences of a venous embolus?
An embolus in the venous system will go onto the vena cava and then through the pulmonary arteries and become lodged in the lungs causing a pulmonary embolism. This means there is decreased perfusion to the lungs.
Through which blood system would an embolus have travelled if it resulted in a pulmonary embolism?
Venous system.
What drug can be used to prevent Thrombosis?
Aspirin.
Define atherosclerosis.
Inflammatory process characterised by hardened plaques in the intima of a vessel wall.
Is atherosclerosis more common in the systemic or pulmonary circulation?
It is more common in the systemic circulation because this is a higher pressure system.
What are the 3 main constituents of an atheromatous plaque?
- Lipids.
- Fibrous tissue.
- Lymphocytes.
Give 5 risk factors for atherosclerosis.
- Cigarette smoking.
- Hypertension.
- Hyperlipidaemia.
- Uncontrolled diabetes mellitus.
- Lower socioeconomic status.
What can be done to prevent atherosclerosis?
Reduce risk factors and taking low dose aspirin regularly.
What is the primary cause of atherosclerosis?
Endothelial cell damage.
Why can cigarette smoking lead to atherosclerosis?
Cigarette smoking releases free radicals, nicotine and CO into the body. These all damage endothelial cells.
Why can hypertension lead to atherosclerosis?
A higher blood pressure means there is a greater force exerted onto the endothelial cells and this can lead to damage.
Define apoptosis.
Programmed cell death of a single cell.
What is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
What protein can switch on apoptosis if DNA damage is present?
p53 protein.
Activation of which family of protease enzymes can turn on apoptosis?
Caspases.
Activation of what receptor can activate caspase and therefore apoptosis?
FAS receptor.
Give an example of a disease where there is a lack of apoptosis.
Cancer; mutations in p53 mean cell damage isn’t detected.
Give an example of a disease where there is too much apoptosis.
HIV.
Define necrosis.
Unprogrammed death of a large number of cells due to an adverse event.
Give 3 examples of events that can lead to necrosis.
- Frost bite.
- Avascular necrosis.
- Infarction.
Give 3 differences between apoptosis and necrosis.
- Apoptosis is programmed cell death whereas necrosis is unprogrammed.
- Apoptosis tends to effect only a single cell whereas necrosis effects a large number of cells.
- Apoptosis is often in response to DNA damage. Necrosis is triggered by an adverse event e.g. frost bite.
Define hypertrophy.
Increase in the size of a tissue due to an increase in the size of constituent cells.
Define hyperplasia.
Increase in the size of a tissue due to an increase in the number of constituent cells.
Define atrophy.
Decrease in the size of a tissue due to a decrease in the size of the constituent cells OR due to a decrease in the number of constituent cells.
Define metaplasia.
A change in the differentiation of a cell from one fully differentiated cell type to another fully differentiated cell type.
Give an example of a disease that demonstrates metaplasia.
Barrett’s oesophagus - the cells at the lower end of the oesophagus change from stratified squamous cells to columnar.
Define dysplasia.
Morphological changes seen in cells in the progression to becoming cancer. The cells become more ‘jumbled up’.
Define acute inflammation.
Initial and short lived tissue reactions to injury.
Define chronic inflammation.
Subsequent and prolonged tissue reactions to injury.
What happens to a cell when the telomere gets too short?
It can no longer divide.
Give an example of:
a) a dividing tissue.
b) a non dividing tissue.
a) Gut or skin tissue can divide.
b) Brain tissue is non dividing.
Why can excision be used as a cure for basal cell carcinoma?
Because BCC doesn’t metastasise.
Suggest a treatment that could be used for leukemia?
Chemotherapy. Leukemia is systemic, it circulates all around the body, therefore excision can’t be used.
Define carcinoma.
Malignant tumour of epithelial tissue.
Give an example of 5 carcinoma’s that can spread to bone.
- Breast.
- Kidney.
- Lung.
- Prostate.
- Thyroid.
Give an example of a carcinoma that can spread to the axillary lymph nodes.
Breast carcinomas.
Why is adjuvant therapy often used in the treatment of carcinomas?
Micrometastes are possible even if a tumour is excised and so adjuvant therapy is given to suppress secondary tumour formation.
Give an advantage and a disadvantage of conventional chemotherapy.
- Advantage: works well for treatment against fast dividing tumours e.g. lymphomas.
- Disadvantage: it is non selective for tumour cells, normal cells are hit too; this results in bad side effects such as diarrhoea and hair loss.
What kind of carcinomas would targeted chemotherapy be most effective against?
Slower dividing tumours e.g. lung, colon and breast.
What is the theory behind targeted chemotherapy?
It exploits the differences between cancer cells and normal cells; this means it is more effective and has less side effects.
What kind of drugs can be used in targeted chemotherapy?
Monoclonal antibodies (MAB) and small molecular inhibitors (SMI).
What is required for a tumour to invade through a basement membrane?
- Proteases.
- Cell motility.
What is required for a tumour to enter the blood stream (intravasation)?
- Collagenases.
- Cell motility.
What is required for a tumour to exit the blood stream (extravasation)?
- Adhesion receptors.
- Collagenases.
- Cell motility.
Give 2 promoters of tumour angiogenesis.
- Vascular endothelial growth factors.
- Fibroblast growth factors.
Give 3 inhibitors of tumour angiogenesis.
- Angiostatin.
- Endostatin.
- Vasculostatin.
What 3 mechanisms do tumour cells use to evade host immune defence in the blood?
- Platelet aggregation.
- Adhesion to other tumour cells.
- They shed surface antigens so as to ‘distract’ lymphocytes.
Give an example of a malignant tumour that often spreads to the lung.
Sarcoma (via venae cavae -> heart -> pulmonary arteries).
Give an example of carcinomas that can spread to the liver.
Colon, stomach and pancreatic carcinomas can spread to the liver via the portal vein.
What causes the pain associated with acute inflammation?
- Stretching and distortion of tissues due to oedema and pus under high pressure in an abscess cavity.
- Chemical mediators e.g. bradykinin and prostaglandins, are also known to induce pain.
Describe the process of neutrophil polymorph migration into tissues as seen in acute inflammation.
- Margination of neutrophils.
- Pavementing of neutrophils.
- Neutrophils pass between endothelial cells.
- Neutrophils pass through basal lamina and migrate into adventitia.
What is the main source of histamine?
Mast cells; histamine is stored in granules in their cytoplasm.
What enzymatic cascade systems does plasma contain?
- The complement system.
- The kinin system.
- The coagulation system.
- The fibrinolytic system.
What is the role of tissue macrophages in acute inflammation?
They 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 therefore reducing swelling. Antigens are also carried to lymph nodes for recognition by lymphocytes.
What is the major role of neutrophil polymorphs in acute inflammation?
Phagocytosis!
Define carcinogenesis.
A multistep process in which normal cells become neoplastic cells due to mutations.
What percentage of cancer risk is due to environmental factors?
85% environmental, 15% genetic.
Give 5 host factors that can affect cancer risk.
- Race.
- Diet.
- Constitutional factors (gender, age).
- Premalignant conditions.
- Transplacental exposure.
Give an example of a situation when transplacental exposure lead to an increase in cancer risk.
The daughters of mothers who had taken diethylstiboestrol for morning sickness had an increased risk of vaginal cancer.
Name the 5 different categories of carcinogens.
- Viral.
- Chemical.
- Ionising and non-ionising radiation.
- Hormones, parasites and mycotoxins.
- Miscellaneous e.g. asbestos and metals.
What causes skin cancer?
Exposure to UV light.
Chemical carcinogens: what types of cancer do polycyclic aromatic hydrocarbons cause?
Lung cancer and skin cancer.
Chemical carcinogens: what can expose people to polycyclic aromatic hydrocarbons?
Smoking cigarettes and mineral oils.
Chemical carcinogens: what types of cancer do aromatic amines cause?
Bladder cancer.
Chemical carcinogens: what types of people are more susceptible to bladder cancer caused by aromatic amine exposure?
People who work in the rubber/dye industry.
Chemical carcinogens: what type of cancer do nitrosamines cause?
Gut cancer.
Chemical carcinogens: what type of cancer do alkylating agents cause?
Leukaemia; the risk is small in humans.
Define neoplasm.
An autonomous, abnormal, persistent new growth.
What is a neoplasm composed of?
- Neoplastic cells.
- Stroma.
Describe neoplastic cells.
Neoplastic cells are derived from nucleated cells. They’re usually monoclonal and their growth is related to the parent cell.
Describe the stroma of a neoplasm.
Connective tissue composed of fibroblasts and collagen; it is very dense. There is a lot of mechanical support and blood vessels provide nutrition for the neoplastic cells.
What is essential for neoplasm growth?
Angiogenesis.
What does a neoplasm release in order to initiate angiogenesis?
Vascular endothelial growth factors.
Why does necrosis often occur in the centre of a neoplasm?
The neoplasm grows quickly and outgrows its vascular supply.
What are the advantages of classifying neoplasms?
It helps to determine the appropriate treatment and prognosis.
What are the two ways in which neoplasms can be classified?
- Behavioural classification.
- Histogenetic classification.
What is the behavioural classification of neoplasms?
Neoplasms can be classified as benign, malignant or borderline. Borderline tumours (e.g. some ovarian lesions) defy precise classification.
What is the histogenetic classification of neoplasms?
Histopathological tests specify tumour type by determining the cell of origin of a tumour. If the origin is unknown the tumour is said to be anaplastic.
What are the 7 main features of benign neoplasms.
- Localised.
- Non-invasive.
- Slow growth, low mitotic activity.
- Close resemblance to normal tissue.
- Normal nuclei.
- Necrosis and ulceration are rare due to slow growth.
- Exophytic growth.
What are the consequences of benign neoplasms?
- Pressure on adjacent structures.
- Obstruction to flow.
- Transformation into malignant neoplasms.
- Anxiety.
What are the 7 main features of malignant neoplasms.
- INVASIVE!
- Metastases.
- Rapid growth, high mitotic activity.
- Resemblance to normal tissue.
- Poorly defined border due to invasive nature.
- Necrosis and ulceration are common.
- Endophytic growth.
What are the consequences of malignant neoplasms?
Destroy surrounding tissue, blood loss due to ulceration, pain, anxiety.
Define carcinoma.
MALIGNANT EPITHELIAL NEOPLASM!
Define sarcoma.
Malignant connective tissue neoplasm.
What is a rhabdomyoma?
Benign striated muscle neoplasm.
What is an adenoma?
Benign tumour of glandular epithelium.
What is a papilloma?
A non-glandular benign tumour.
What is a leiomyoma?
A benign smooth muscle neoplasm.
What is a neuroma?
A benign neoplasm of nerves.
What is a chondrosarcoma?
A malignant neoplasm of cartilage.
What is a liposarcoma?
A malignant neoplasm of adipose tissue.
What is a melanoma?
A malignant neoplasm of melanocytes.
What is a lymphoma?
A malignant neoplasm of lymphoid cells.
What is a mesothelioma?
A malignant neoplasm of mesothelial cells.
Carcinomas and sarcomas are further classified according to the degree of differentiation. Is a carcinoma/sarcoma with a close resemblance to normal tissue classified as well differentiated or poorly differentiated?
A carcinoma/sarcoma with a close resemblance to normal tissue is classified as well differentiated. These types of neoplasms are low grade and have a better prognosis.
What must the immune system do in order to be effective?
The immune system has to discriminate self from non-self.
Describe innate immunity.
Non-specific, instinctive, present from birth, first line of defence. It is focused around physical and chemical barriers and phagocytosis. No lymphocyte involvement.
Give examples of physical and chemical barriers used in innate immunity?
Skin, mucociliary escalator, gastric acid, hairs, lysozymes etc.
What is the function of lysozyme?
It destroys bacterial cell walls.
Describe adaptive immunity.
Specific, requires lymphocytes. Memory and quicker response.
Give examples of 3 polymorphonuclear leukocytes.
- Neutrophils.
- Basophils.
- Eosinophils.
Give examples of 3 mononuclear leukocytes.
- Monocytes.
- B lymphocytes.
- T lymphocytes.
In which primary lymphoid tissue do T cells mature?
Thymus.
In which primary lymphoid tissue do B cells mature?
Bone marrow.
How do T cells recognise antigens?
For T cells to recognise antigens they must be displayed by an antigen presenting cell and bound to MHC1/2. T cells can’t recognise soluble antigens.
What is the function of T helper 1 (CD4)?
It helps the immune response against intracellular pathogens. Secretes cytokines.
What is the function of T helper 2 (CD4)?
It helps produce antibodies against extracellular pathogens. Secretes cytokines.
What is the function of Cytotoxic T cell (CD8)?
It can kill cells directly by binding to antigens; they induce apoptosis.
What is the function of T reg (FoxP3)?
They regulate the immune response.
Which cells express MHC1?
All nucleated cells express MHC1. e.g. a virus infected or cancer cell would express MHC1.
Which cells express MHC2?
Antigen presenting cells ONLY e.g. macrophages, B cells, dendritic cells.
Which MHC would an intracellular antigen (endogenous) lead to the expression of?
MHC1.
Which MHC would an extracellular antigen (exogenous) lead to the expression of?
MHC2.
What type of T cell binds to MCH1?
Cytotoxic T cells (CD8).
What type of T cells binds to MCH2?
Helper T cells (CD4).
What do B cells differentiate into?
Plasma cells. The plasma cells then produce antibodies.
What does a helper T cell bind to?
A T cell receptor which is bound to an antigen epitope which is bound to MHC2 on an APC.
Which interleukin is secreted when a helper T cell is bound to a T cell receptor?
IL-2. This then binds to an IL-2 receptor on the T cell and produces a positive feedback mechanism leading to division and differentiation.
How many antibodies can each B cell make?
Each B cell can only make 1 antibody. This 1 antibody can only bind to 1 epitope.
What happens to B cells that recognise ‘self’?
They are killed in bone marrow.
Describe the process of a T helper cell binding to a B cell.
A B-cell antibody binds an antigen -> phagocytosis -> epitope is displayed on the surface of the B-cell bound to an MHC2 -> TH2 binds to B-cells -> cytokine secretion induces B-cell clonal expansion -> differentiation into plasma cells and memory B cells.
Give 3 functions of antibodies.
- Neutralise toxins.
- Opsonisation.
- Activate classical complement system.
Which immunoglobulin is found in breast milk and other secretions?
IgA.
What are the 2 most common immunoglobulins?
IgG and IgM.
Which region of an antibody binds antigens?
The fab region.
Which region of an antibody binds to B cells?
The Fc region.
Name 4 types of cytokines.
- Interferons.
- Interleukins.
- Colony stimulating factors.
- Tumour necrosis factors.
What is the function of interferons?
Interferons produce antiviral proteins.
What is the function of interleukins?
Interleukins cause cell division and differentiation.
What is the function of colony stimulating factor (CSF)?
CSF causes division and differentiation of bone marrow stem cells.
What is the function of tumour necrosis factor (TNF)?
TNF mediates inflammation and cytotoxic reactions.
What is the function of chemokines?
Chemokines attract leukocytes to sites of infection.
Give examples of secondary lymphoid tissue.
The spleen, lymph nodes, mucosa associated lymphoid tissue - MALT.
Describe the process of phagocytosis.
- Pathogen binds to neutrophil/macrophage.
- Engulfment of pathogen.
- Phagosome formation.
- Lysosome fusion - phagolysosome.
- Pathogen is destroyed.
Give 3 examples of O2 dependent mechanisms of killing.
- Killing using reactive oxygen intermediates.
- Superoxides can be converted to H2O2 and then to hydroxyl free radicals.
- NO leads to vasodilation and increased extravasation and so more neutrophils etc are in the tissues to destroy pathogens.
What is the role of NO in killing pathogens?
NO leads to vasodilation and increased extravasation. This means more neutrophils etc pass into the tissues to destroy pathogens.
Why can superoxides be used to destroy pathogens?
Superoxides can be converted to H2O2 and then to hydroxyl free radicals. Hydroxyl free radicals are highly reactive and can destroy pathogens.
What mechanisms or cells are involved in O2 independent killing?
Defensins, lysozyme, pH, TNF.
Where are complement system plasma proteins derived from?
The liver.
What are the 3 main outcomes of complement system activation?
- Pathogen lysis.
- Increased phagocytosis.
- Activation of leukocytes.
What activates the classical complement pathway?
Antibodies.
Briefly describe the classical complement pathway.
- C1s cleaves C4 -> C4a and C4b.
- C4b binds C2b forming C4b2b. C4b2b is a C3 convertase and is responsible for C3 -> C3a and C3b.
- C4b2b binds C3b forming C4b2b3b.
- C5,6,7,8 and 9 also bind and eventually you get MAC formation. MAC is a pore like channel in a membrane.
What compound prevents excessive activation of the classical complement pathway?
C1 inhibitor.
- C1 inhibitor leads to a negative feedback loop.
What activates the lectin pathway?
Mannose binding protein.
What activates the alternative pathway?
Bacterial cell walls and endotoxin.
What are the 3 different pathways that make up the complement system?
- Classical.
- Lectin.
- Alternative.
Briefly describe the alternative pathway.
- C3 reacts slowly with H2O forming C3(H2O).
- C3(H2O) binds factor B. This becomes a substrate for cleavage by factor D.
- Factor B is split into Bb and Ba.
- Bb sticks to C3(H2O) forming C3(H2O)Bb.
5.C3(H2O)Bb is a C3 convertase that cleaves C3 into C3b and C3a. - C3b then binds to pathogens and causes opsonisation for improved phagocytosis. Also leads to MAC formation.
Which complement plasma proteins have opsonic properties when bound to a pathogen?
C3b and C4b.
What is the function of MAC in a pathogens’ membrane?
MAC is a leaky pore like channel. Ions and water pass through the channel and disrupt the intracellular microbe environment -> microbe lysis.
Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes etc?
C3a and C5a.
What kind of immunity are PRR’s and PAMP’s associated with?
Innate immunity.
What are PRR’s a receptor for?
PAMP’s.
Name 3 receptors that make up the PRR family.
- Toll-like receptors (TLR).
- Nod-like receptors (NLR).
- Rig-like receptors (RLR).
What is the main function of TLR’s?
TLR’s send signals to the nucleus to secrete cytokines and interferons. These signals initiate tissue repair. Enhanced TLR signalling = improved immune response.