Introduction to Clinical Science Flashcards
What are the 4 signs of inflammation?
Rubor - redness
Calor - heat
Tumor - swelling
Dolor - pain
What is inflammation?
A reaction to injury or infection involving cells such as macrophages and neutrophils
What is the difference between Acute and Chronic inflammation?
Acute - short lasting, sudden, usually resolves.
Chronic - long lasting, slow onset, may not resolve
Give one example of Chronic and acute inflammation
Acute - Appendicitis
Chronic - TB
What cells are involved in inflammation?
Neutrophils Macrophages Lymphocytes Endothelial cells Fibroblasts
What is the role of Neutrophils in inflammation?
Cytoplasmic granules w/ enzymes to kill bacteria and can signal for macrophages.
They are the first there and first to die at the site.
What is the role of Macrophages in inflammation?
Long lasting, phagocytic and can present antigens.
They ingest bacteria and carry it away.
What is the role of Lymphocytes in inflammation?
Long lasting - produce chemicals to attract other inflam cells.
They provide immunological memory for past infections.
What is the role of Endothelial cells in inflammation
They line capillary blood vessels.
They become sticky, allowing adhesion of inflam cells, can also become porous to let cells pass into tissue.
Is inflammation always good?
It can be during infection/injury.
It is problematic in hypersensitivity reactions or AI disease.
What are endogenous chemical mediators of inflammation (with examples)
They are secreted and mediate the inflammatory response.
Examples - histamine, prostaglandins, bradykinin and Nitric Oxide.
How would you treat inflammation?
You need to treat the route cause e.g. bact infection w/ antibiotics.
You would prescribe NSAIDs which inhibit prostaglandin synthetase.
You could also prescribe Corticosteroids to down regulate chemical mediators.
Why might somebody be refered for an autopsy?
Medico legal reasons - coronial
Hospital autopsy - teaching/confirmation of COD.
(Presumed natural, presumed unnatural and presumed iatrogenic)
Who can make request an autopsy?
Relatives, police, registrar of BDM, coroner.
What is an embolus?
Mass of material in the vascular system able to become lodged within a vessel and block it.
What are three causes of Emboli?
Thrombus
Air
Cholesterol Crystals
How do the lungs act as a filter for venous emboli?
BV from the lungs are capillaries which means that it cannot reach the arteries as it will get caught in the vein/cap network.
What is Thrombosis?
solid mass of blood constituents formed within an intact vascular system during life.
What is Virchow’s triad?
Reasons for Thrombotic formation
Change in vessel wall
Change in blood flow
Change in blood constituents
Process of Thrombus formation
- Damage to endothelial cells cause platelets to stick to collagen –> Platelet aggregation, + Feedback
- Endothelial injury disrupts laminar flow
Formation of a thrombus causes fibrin polymerase to be released –> keeps it together.
What is the reason clots are fairly rare?
Laminar flow - blood travels in the center and doesn’t touch the side.
Endothelial cells are not sticky when healthy.
What are the outcome of Thromboses?
Break down and lysis
Recanalisation - new capillaries grow through it
Break off and embolise
How can you prevent thrombosis?
Exercise
Stockings
Aspirin - inhibits platelet aggregation.
What is Ischaemia?
Reduction of blood flow to a tissue without any other implications.
What is the risk of Reperfusion post ischaemia?
Can produce super oxide radicals which damage the cells.
What is the difference between Ischaemia and Infarction?
In Ischaemia there is reduction of blood flow w/o implications and in infarction there is tissue death.
What is Infarction?
Reduction in blood flow means that cell’s cannot support maintenance and will die.
Is Infarction always deadly?
No
Some organs have two artery supplies e.g. COW, Liver, Lung whereas others only have one.
What is usually the cause of infarction?
Thrombosis breaking off from other areas or a tumour.
What is granulation tissue?
Composed of small BV in a connective matrix with myofibroblasts.
What is a granuloma?
An aggregate of epitheliod histocytes
What are the definitions of Resolution and Repair?
Resolution - initiating factor is removed and the tissue regenerates.
Repair - the initiating factor is still present, tissue is damaged and unable to regenerate.
What cells can regenerate?
Hepatocytes Pneumocytes All blood cells Epithelium of Gut and Skin Osteocytes
What cells cannot regenerate?
Myocardial cells
Neurones
What is the process of Repair?
replacement of damaged tissue by fibrous tissue which is collagen produced by fibroblasts.
What produces collagen?
Fibroblasts
What is lobar pneumonia?
Pneumonia specific to one lobe in the Lungs, can recover as pneumocytes can regenerate.
What is the process of Skin repair?
Abrasion - scab formation - epidermis grows and is protected by the scab.
What is the process of Skin repair post surgery?
Exudation of fibrinogen causes a weak fibrin joint. Epidermal growth causes collagen synthesis –> stronger collagen joint
What is Atherosclerosis?
A disease in which plaque builds up in the artery.
Who tends to get Atherosclerosis more often?
Men in industrial areas.
Where do Atheroma’s develop?
In arteries with high pressure, e.g. the aorta, and less in the arteries with low pressure e.g. pulmonary arteries.
What increases the risk of Atherosclerosis?
Smoking - damages endothelium using free radicals
Hypertension - shearing forces on endothelial cells
Diabetes ( poorly controlled) - super anions damage cells
Hyperlipidaemia - direct damage to endothelial cells.
What is the Endothelial Damage theory?
Recurrent endothelial cell injury causes microthrombi formation which builds atheroscleroma over years.
What are some of the Complications of Atherosclerosis?
MI
Gangrene
Peripheral Vasc disease
Aneurysm
How can you reduce the risk of Atherosclerosis?
Low dose aspirin can prevent platelet aggregation.
What is Apoptosis?
Programmed cell death
What is Necrosis?
Traumatic cell death which is unprogrammed
What are some examples of Necrosis?
Avascular necrosis of bone
Pancreatitis
Frost bite
What are the different types of Necrosis?
Caseous necrosis - linked w/ TB
Liquifactive necrosis - thin liquid
Coagulation necrosis - thick and goey
What is a disease in which too much apoptosis occurs?
HIV (gets rid of T helper cells)
What is a disease in which too little apoptosis occurs?
Cancer
What protein Initiates apoptosis?
P53
What is the role of Capases?
They are the effectors of apoptosis
What are the effectors of apoptosis?
Capases
What switches on Capases?
BAX protein
What switches off Capases?
Bcl2 protein
What can trigger apoptosis?
DNA damage
What is the process of apoptosis?
- A trigger causes a release of enzymes
2. These enzymes cause the nucleus to shrink and organelles are carried out by vesicles
Why don’t adult cells divide very often?
The telomeres get shorter after every division.
What causes cells to ‘wear out’?
Free radical generation
Free radical absorption
Cross linking of proteins via UV light
Shortening telomeres
What are some diseases associated with aging?
Deafness –> Ciliated hair cells are not replaceable
Osteoporosis - bone matrix is decreased
Senile dementia –> brain atrophy
Sarcopenia –> loss of skeletal muscle mass
Define congenital
Present at birth
Define Inherited disease
Caused by an inherited genetic abnormality, not always present early e.g. huntingtons
Define acquired disease
caused by non-genetic environmental factors e.g. FAS
What is a homeobox gene?
A gene sequence that codes for different parts of the body.
What is Mendelian inheritance?
Single gene inheritence
What is autosomal inheritance?
Non sex cell, autosomal dominant (FAP) and recessive (CF)
What is polygenic inheritance?
When one characteristic is associated with two or more genes.
What is Hypertrophy, with an example?
Increase in size of tissue caused by an increase in size of constituent cells.
e.g. Muscles getting bigger.
What is Hyperplasia, with an example?
Increase in size of a tissue caused by an increase in number of the constituent cells
e.g. Benign prostatic hyperplasia.
What is Atrophy, with an example?
Decrease in size of a tissue caused by a crease in the number of constituent cells or a decrease in their size .
e.g. Muscular atrophy and alzheimers.
What is metaplasia, with an example?
Change in differentiation of a cell from one fully differentiated type to a different fully differentiated type.
e.g. change from cilliated columnar epithelium to squamous in bronchi (barretts oesophagus thanks to smoking)
What is Dysplasia, with an example?
Imprecise term for the morphological changes seen in the progression to becoming cancer.
e.g. epithelial cells changing as a precursor to cancer.
Define carcinogenesis.
The transformation of normal cells to neoplastic cells through permanent alterations/mutations.
Define Oncogenesis
Formation of benign and malignant tumours
Define Mutagenic
Something which acts on the DNA
How much of cancer is due to the environment?
85%
What are some behavioral risks of cancer?
Smoking - Lung cancer
Rubber industries - bladder cancer
What is radiating energy?
ionising radiation w/ long term effects
e.g. Thyroid cancer post chernobyl and exposure to UV –> Increase in skin cancer, BCC and melanoma
What are the classes of Carcinogens?
Chemical Viral Ionising/non ionising radiation Host Miscellaneous
What is a chemical carcinogen?
It has no common structure, some act directly some need to be metabolised from pro-carcinogenic to ultimate carcinogenic.
Examples of Chemical carcinogens
Polycyclic aromatic HC - lung and skin cancer - smoking
Aromatic amines - bladder cancer - rubber workers
Nitrosamines - gut cancer
Alkylating agents - Leukaemia
Miscellaneous examples of carcinogens
Asbestos and metals
What are Host factors?
Race - oral cancer in indians
Diet
Constitutional factors - increases w/age, inherited predisposition + gender
premalignant lesions - Ulcerative collitis
What are the Biological factors?
Hormones - Oestrogen - mammary/endometrial cancer
Mycotoxins - alfatoxin B1 - Hepatocellular Carcinoma
Parasites - Clonorchis sinesis - Cholanginocarcinoma
What does Asbestos cause?
Malignant Mesothelioma
Lung cancer
Asbestosis
What is Basal cell carcinoma and how would you treat it?
Only invades the skin locally, doesn’t spread to other parts of the body. You can excise it locally.
How is leukemia spread around the body?
WBC circulate around the body and so will any tumour of the WBC.
Chemotherapy is the appropriate treatment
What is a Carcinoma?
They spread to the lymph nodes that drain the site of the carcinoma (can spread from blood to bone)
What cancers can be spread from blood to bone?
Breast Prostate Lung Thyroid Kidney
How would you treat Breast cancer?
- Confirm the cancer using a biopsy
- Check if its spread to the axilla - if so clear it.
- if it’s spread to the body chemo
- If it hasn’t surgery w/wo axillary clearence
What is adjuvant therapy?
Extra treatment given post surgical excision to prevent a secondary tumour.
What is the route of mets?
- Through BM to EC
- EC to vessels, travels in to the vessels
- Adheres and breaks int othe EC then grows
What is the growth of mets limited to, and what is it dependent on?
1mm in diameter.
GF and blood supply
What is required to invade the basement membrane?
Requires collagenase and cell motility
Collagenase required to break through the collagen layers of the BM
What is required to enter the blood stream (Intravasation)?
Collagenase + cell motility
What is required to exit the blood stream?
Adhesion
Cell motility
Collagenase