ICA Flashcards
Another name for acute inflammation
Neutrophil mediated inflammation
Another name for chronic inflammation
Macrophage/lymphocyte mediated inflammation
What are neutrophil polymorphs
White blood cells made in the bone marrow
They are called polymorphs because they have a polylobed nucleus
what is the lifespan of neutrophil polymorphs
very short lifespan, 2 or 3 days
What is the function of neutrophil polymorphs?
They phagocytose debris and bacteria and contain bags of enzymes (lysosomes) which can be used to kill and digest phagocytosed bacteria
Neutrophils are the first cells to arrive at the site of acute inflammation. They often die at the site of inflammation and are themselves phagocytosed by macrophages
What are macrophages?
Are also white blood cells
What is the lifespan of macrophages?
much longer lifespan than neutrophils, months to years.
Function of macrophages
also phagocytose debris and bacteria.
They also transport material to lymph nodes and may present the material to lymphocytes so a secondary immune reaction is induced.
What are lymphocytes?
What are the functions of lymphocytes?
Are long-lived cells (years) which produce chemicals involved in controlling inflammation and antibodies (from B lymphocyte plasma cells)
Lymphocytes are the immunological memory of the body ready to scale up defence against micro-organisms that have infected the body before
What are fibroblasts? And function?
Produce collagenous connective tissue in scarring following some types of inflammation
Sequence of acute inflammation
• injury or infection
• neutrophils arrive and phagocytose and release enzymes
• macrophages arrive and phagocytose
• either resolution with clearance of inflammation or por- gression to chronic inflammation
• examples of acute (neutrophil-mediated) inflammation
acute appendicitis, frostbite, Streptococcal sore throat
Sequence of chronic inflammation
either progression from acute inflammation or starts as ‘chronic’ inflammation such as infectious mononucleosis (thus better term is macrophage/lymphocyte-mediated inflammation)
• no or very few neutrophils
• macrophages and lymphocytes, then usually fibroblasts
• can resolve if no tissue damage (e.g. viral infection like glandular fever) but often ends up with repair and for- mation of scar tissue
What type of inflammation are granulomas involved in?
particular type of chronic inflammation with collections of macrophages/histiocytes surrounded by lymphocytes
When are granulomas significant?
due to myobacterial inefction such as TB or leprosy
• also seen in Crohn’s disease and sarcoidosis
• may be seen around foreign material in tissue
What prevents blood clots forming all the time?
- 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.
What is thrombosis?
is the formation of a solid mass from blood constituents in an intact vessel in a living person
What are the stages of thrombosis?
The first stage of thrombosis is 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
Why is it difficult to stop clotting once started?
Both these reactions on prev flashcard involve positive feedback loops so that once they have started they are difficult to stop.
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.
What 3 factors cause thrombosis?
Change in vessel wall
Change in blood flow
Change in blood consistents
What is embolism?
Is the process of a solid mass (thrombus) in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel
Name some less common causes of embolus
Air
Cholestral crystals
Tumour
Amniotic fluid
Fat
What would happen if an embolus enters the venous system?
If an embolus enters the venous system it will travel to the vena cava, through the right side of the heart and will lodge somewhere in the pulmonary arteries (depending on its size)
Why can’t an embolus, that has entered venous circulation, then get through arterial circulation?
because the blood vessels in the lung split down to capillary size (through which only single red blood cells can squeeze) so the lungs act as a filter for any venous emboli.
What happens if an embolus enters the arterial system?
it can travel anywhere downstream of its entry point lead to gangrene, MI, stroke
What ischemia?
reduction blood flow to a tissue without any other implications
What is infarction?
Reduced blood flow to a tissue leading to subsequent cell death
What usually causes infarction?
Thrombosis
Why are organs with end arterial supply more susceptible to infarction?
As these organs have a single artery supplying them so they are very suscep- tible to infarction of this supply is interrupted
Name organs with dual arterial supply
Lung- pulmonary vein and bronchial artery
Liver- hepatic portal vein and hepatic artery
Some parts of the Brian under the circle of Willis
Define resolution
Initiating factor is removed
Tissue is undamaged/ able to regenerate
Examples of resolution
In the liver- if the damage isn’t chronic
Superficial cut of skin
Define repair
Initiating factor is still present
Tissue is damaged and unable to regenerate
What is involved in repair
Replacement of damaged tissue by fibrous tissue
Collagen produced by fibroblasts
Examples of repair
Heart after myocardial infarction
Brian after cerebral infarction
Spinal cord after trauma
Deeper cut of skin or scar
Name cells that regenerate
Hepatocytes
Osteocytes
Pneumocyte’s
Blood cells
Gut and skin epithelium
Name cells that do not regenerate
Myocardial cells
Neurones
What is atherosclerosis?
Inflammatory process characterised by hardened plaque formation in the intima of the vessel
How does atherosclerosis cause illness?
by reducing the blood flow in im- portant areas e.g. myocardial infarction in the heart
Time course of atherosclerosis
• birth - no atherosclerosis
• late teenage/early 20s - fatty streaks in aorta, may not progress to established atherosclerosis
• 30s/40s/50s - development of established atherosclerotic plaques
• 40s-80s - complications of atherosclerotic plaques e.g. thrombosis, intraplaque haemorrhage
Risk factors for atherosclerosis
Cigarette smoking
Hypertension
Hyoerlipidemia
Uncontrolled diabetes mellitus
Low socioeconomic background
What causes atherosclerosis?
Damage of endothelial cells
What is a complication of atherosclerosis?
If an atherosclerotic plaque completely blocks an artery then no blood will flow to the organ supplied by that artery and (unless there is a second arterial supply which is unusual in the body) the organ will die (infarct)
What is the effect of pieces of an atherosclerotic plaque breaking off and travelling downstream to block smaller vessels (embolism)?
This may cause small infarcts distal to the main atherosclerotic plaque and over time these cumulative effect of these small infarcts can be significant
What is apoptosis?
Is programmed cell death that takes place in single cells
This prevents cells with accumulated genetic damage from dividing and producing cells which may eventually develop into cancer cells
How does a cell decide to apoptosis?
One of the mecha- nisms is detecting amount of DNA damage within the cell.
Which protein in cells detects DNA damage?
p53 protein
How does a cell apoptosis?
The cell triggers a series of pro- teins which lead to the release of enzymes within the cell which eventually autodigest the cell.
What is the name of these enzymes?
Capsases
When is apoptosis important in functioning of the body?
Development- remove of cells during development eg. 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
How is apoptosis linked to cancer?
cells in tumours often don’t apoptose when they would have been expected to which results in in- crease in the tumour size and accumulation of genetic mutations.
Why does this occur in cancer?
Mutation in p53 gene so the p53 protein can no longer detect DNA damage and instigate apoptosis
What happens to apoptosis in HIV?
Too much apoptosis- it can induce apoptosis in CD4 helper cells which reduces their num- bers enormously to produce an immunodeficient state
What is necrosis?
Unprogrammed death of a large number of cells due to an adverse event
Examples of necrosis
Frostbite
Avascular necrosis
Infarction due to loss of blood supply
Pancreatitis
Toxic venom from reptiles and insects
What happens after necrosis?
all the body can do is try to clear up the mess by macrophages phagocytosing dead cells and usually by replacing the necrotic tissue by fibrous scar tissue (un- less the tissue can regenerate).
What is caseous necrosis?
can be due to tuberculosis
Define hypertrophy
Increase in the size of an organ due to increase in size of its constituent cells
Where does hypertrophy occur?
In organs where cells cannot divide
Examples of hypertrophy
Skeletal muscle in athletes/bodybuilders
Define hyperplasia
Increase in the size of an organ due to increase in the number of its constituent cells
Where does hyperplasia occur?
Organs where cells can divide
Examples where hyperplasia occurs
Benign prostatic hyperplasia, endometrial hyperplasia
What is mixed hypertrophy/ hyperplasia?
Increase in the size of an organ due to increase in size and number of its consistent cells
Where does hypertrophy/hyperplasia occur?
Organs where cells can divide
Examples of mixed hypertrophy and hyperplasia
Smooth muscle cells of the uterus during pregnancy
What is atrophy?
Decrease in size of an organ due to decrease in size or number of its consistent cells or both
Examples of atrophy
Alzheimer’s dementia
Define metaplasia
Change in cell differentiation from one fully differentiated cell type to another fully differentiated type
What causes metaplasia?
Consistent change in the environment of an epithelial surface
Examples of metaplasia
Barrett’s oesophagus
Define dysplasia
Morphological changes that may be seen in cells in the progression on to development of cancer
How does dysplasia lead to cancer?
From mild dysplasia, to moderate, to severe, carcinoma in situ and eventually invasive cancer
Examples of dysplasia
Bronchial epithelium in cigarette smokers
Is there a limit to how many times a human cell can divide?
Yes
Why do skin cells from older people will divide less times in culture than those from younger people?
This is because at each cell division the telomere region at the end of chromo- somes shortens and eventually becomes so short that it is not possible for the chromosomes to divide and replicate so the cell can no longer divide
What effects telemore length?
Paternally inherited
Why do non dividing cells die once they have accumulated a certain amount of damage to their cellular systems?
Because they are unable to divide
Anything that reduces damage to cells can reduce the effects of aging and prolong life
How does calorie restriction slow down aging?
As calorie restriction reduces these metabolic products
How can aging be reduced in certain areas of body?
Local measures such as SPF for protection of skin from skin
Which parts of the body are specifically effected by aging?
Skin
Eyes
Osteoporosis
Dementia
Loss of muscle (sacropaenia)
Deafness
Why causes wrinkling of the skin?
UV-B light causing cross linking of the proteins, especially collagen in the dermis
How can skin wrinkling be avoided?
avoid- ing too much sun exposure
using high sun protec- tion factor cream
What causes cataracts in eyes?
UV-B cross linking of proteins in the lens causing opacity
How can cataracts be prevented?
wearing sunglasses that cut out UV light
What is osteoporosis?
loss of bone matrix predominantly in women after the menopause
How can osteoporosis be prevented?
prevented by hor- mone replacement therapy at menopause and calcium/ vitamin D supplements
What causes loss of muscles (sacropaenia)?
Reduced levels of growth hormone and testosterone in later life
What causes deafness?
the hair cells in the cochlear do not divide so if they are damaged by high volumes they will die and not be replaced eventually producing deafness
Where do basal cell carcinoma of the skin only invade?
Locally- it never shreds to other parts
What is a cure of basal cell carcinoma?
Complete local excision
White blood cells circulate round the body
So any tumour of white blood cells also travel round the body
How can carcinomas spread- to where?
Carcinomas spread to lymph nodes that drain the sit of the carcinoma
can be beneficial as a way to kill cancer
However if cancer has spread viscously, eg from breast to axillary lymph nodes, to lymph y nodes must be removed
How can carcinomas spread?
Spread through the blood to bone
What cancers are commonly spread to bone?
Breast
Kidney
Lung
Prostate
Thyroid
Why is adjuvant therapy often used in treatment of carcinomas?
Micrometastes are possible even if the tumour is exited and so adjuvant therapy is given to suppress secondary tumour formation
What is adjuvant therapy?
Extra treatment given after surgical excision
Eg radiotherapy, chemotherapy
Define carcinogenisis
A multi step transformation of normal cells to neoplastic cells though permanent genetic alterations or mutations
What does carcinogeneis apply to?
Applies to malignant neoplasms
What does oncogenesis apply to?
Benign and malignant tumours
What are carcinogens?
Agents known or suspected to cause tumours
define carcinogenic
Cancer causing
Define oncogenic
Tumour causing
What are the percentage of the two categories of causes of cancer?
85% environmental. 15% genetic
Viral carcinogens
Image
RNA carcinogens
Image
Define proto-oncogenes
These are genes which promote cell growth and survival, therefore promoting carcinogenesis
Define tumour suppressor genes
These are genes which inhibit cell growth and proliferation, playing a role in inhibiting carcinogenesis
What are the TNM staging?
• T= Tumour
Usually determined by tumour size and extent or depth of spread
•N = nodes
Extent of lymph node metastases
•M = metastases
Extent of spread to other parts of the body
What are modes of metastases?
Direct
Lymphatic
Blood vessel
Transcoeleomic
