ICS Flashcards
What is the main cell involved in acute inflammation and what are the 3 stages of migration?
What happens at the site of inflammation?
- Margination, adhesion (selectins), emigration/diapedesis
Differences between an arterial and venous ulcer
Location
Arterial- usually on the tips of toes and lateral malleolus of ankle
Venous - usually on the medial malleolus and inner calf
Exudate
Arterial - punched out hole (deeper) with little exudate
Venous - less demarcated punched out hole appearance (shallower) with a lot of exudate
Colour
Arterial - pale cool skin (or yellowish-grey base)
Venous - Reddish base
Skin changes
Arterial - hair loss, thickened toenails, weak distal pulse of affected limb
Venous - Varicose veins, itchy skin, eczematous (stasis dermatitis)
What is virchow’s triad and what are its components?
The formation of a thrombus is dependent on any one of Virchow’s triad being present
1) Abnormal blood flow (stasis/decreased blood flow) - due to e.g. periods of immobility (long flights/being bed bound) –> Most common caused of DVT
2) Abnormal blood components (Hypercoagulability - excessively easy clotting of blood) –> alterations in the constitution of blood caused by smoking, sepsis (reaction to an infection), malignancy/cancer – can be due to genetics also - Gene mutations like in essential thrombocythemia (high number of platelets in blood)
3) Abnormal blood vessel wall (Endothelial injury) –> can be from NICOTINE (smoke), atheroma formation (Fatty substance build up in arteries), inflammatory response, surgery, direct trauma, etc.
atheroma = plaque
What are plaques that build up in arteries composed of?
Lipid, smooth muscle, macrophages + foam cells (macrophages that ingest LDLs), platelets, calcium, fibroblasts, T lymphocytes
Lipid, necrotic core, connective tissue, fibrous cap.
What is atherosclerosis?
- The accumulation of fibrolipid plaques in systemic arteries. It narrows the arteries, reducing blood flow to important areas and thus cause illness e.g. MI of the heart
Take note: not really found in low pressure systems (pulmonary arteries). common in high pressure systems (aorta/systemic arteries)
Describe the formation of an atherosclerosis
Look into lectures about smooth muscle cap.
1) Fatty streak –> Precursor turns into plaque (late teenage/early 20s) (consists of lipid laden macrophages and T lymphocytes within the INTIMAL layer of the vessel wall)
2) Lipid accumulation –> Endothelial damage initiates an INFLAMMATORY response. This results in monocytes and macrophages being recruited to phagocytose LDLs to become foam cells, which contribute to plaque formation.
3) Platelet aggregation (due to damage of endothelial lining) –> Accumulated lipids lead to plaque protruding into the artery lumen, causing platelet aggregation
4) Smooth muscle cells contribute to the formation of the fibrous cap over the plaque by releasing fibroblast growth factor producing collagen and elastin. (stabilising the plaque - stable atheroma)
atheroma=plaque
What are some risk factors for atherosclerosis?
Smoking, diabetes, hypertension, obesity, hyperlipidemia increased age, males
(Also risk factors for MI)
Name a few possible complications of atherosclerosis
- Cerebral infarction
- Myocardial infarction
- Emboli (when pieces of the atherosclerotic plaque break off and travel downstream to smaller vessels) –> can cause transient ischemic attacks or cerebral infarcts if in the carotid artery (carotid atheroma)
- Aortic aneurysm (if atherosclerosis occurs in the aorta, it can weaken the wall of the aorta causing it to be less elastic and causing turbulent blood flow.
- Gangrene (lack of blood flow and lack of oxygen to extremities can lead to necrosis)- body tissue dies (usually starts in the toes)
- Intermitted claudication (muscle pain due to lack of oxygen)
State 4-5 differences been apoptosis and necrosis
for point 4 need to check with lectures
Apoptosis –> Non inflammatory, programmed cell death
Necrosis –> Inflammatory, traumatic cell death (due to injury, disease initiated, etc)
Apoptosis –> Cell membrane remains intact
Necrosis –> Disrupted cell membrane (loss of membrane integrity)
Apoptosis –> Cell shrinks (nucleus condenses)
Necrosis –> Cell swells (and bursts)
Apoptosis –> Chromoatin is unaltered. Pyknosis (condensation of chromatin) and Karyorrhexis (fragmentation of the nucleus)
Necrosis –> Chromatin is altered - degrades and fragments(could mutate). Pyknosis, karyorrhexis and karyolysis occurs (dissolution of cytoplasm)
Apoptosis –> Energy dependent process (and therefore controlled)
Necrosis –> Energy independent
How does a cell decide to apoptose?
Why does this not work in cancer cells?
What happens in HIV?
- Via the amount of DNA damage within the cell. p53 is a protein that can detect DNA damage and can then trigger apoptosis.
- In cancer cells, there is a mutation of the p53 protein so it can no longer detect DNA damage and induce apoptosis.
- In HIV, the HIV virus can induce apoptosis in CD4 helper cells which reduce their numbers, resulting in an immunodeficient state.
What is atherosclerosis?
- The accumulation of fibrolipid plaques in systemic arteries. It narrows the arteries, reducing blood flow to important areas and thus cause illness e.g. MI of the heart
Take note: not really found in low pressure systems (pulmonary arteries). common in high pressure systems (aorta/systemic arteries)
Describe the apoptosis intrinsic pathway.
Occurs due to internal stimuli (DNA damage, biochemical stress, lack of growth factors)
- Pathway modulated by the molecules Bcl-2 (inhibits Bax) and Bax (promotes cytochrome C release)
- Cytochrome C activates caspases - the executioners of apoptosis
Describe the apoptosis cytotoxic pathway
Cytotoxic T cells release granzyme B and perforin which activate caspases for apoptosis. (perforin creates pores or channels in the target’s cell membrane for granzyme B to enter the cell and activate caspases)
Define hypertrophy and hyperplasia
Hypertrophy –> Increase in size of an organ caused by an increase in the size of its constituent cells (without an increase in number) - skeletal muscle in atheletes
Hyperplasia –> An increase in the size of an organ due to an increase in the number of its constituent cells - BPH
What is the hayflick limit and why is it a thing?
Hayflick limit - The limit to which a human cell can divide.
There is a limit because at each cell division, the telomere region at the end of chromosomes shortens and eventually becomes so short that it is not possible for chromosomes to divide and replicate. (telomere length appears to be paternally inherited)
Definition of carcinogenesis and neoplasm
Carcinogenesis –> The transformation of normal cells into neoplastic cells (cancer cell) through permanent mutation leading to uncontrolled/abnormal growth (possibly into a tumour subsequently)
Neoplasm –> The Autonomous, abnormal, persistent new growth of cells
What does a neoplasm consist of?
Stroma and neoplastic cells
Carcinoma definition
Malignant epithelial neoplasm
What are the characteristics of a neoplastic cell?
Autocrine growth stimulation - due to overexpression of growth hormone and mutation of tumour suppression genes. - very fast growth
They can evade apoptosis
They have telomerase - Prevents telomere shortening with each replication
Sustained angiogenesis - They have their own blood supply
Difference between benign and malignant tumour (behavioural classification of neoplams- benign, borderline, malignant)
Malignant - Endophytic, poorly circumscribed, ulceration, hyperchromic nuclei
Benign - Exophytic, well circumscribed, rare ulceration, normal shaped nuclei
What are tumours called when they are non/glandular benign/malignant?
They are Epithelial tumours
Papilloma - non glandular benign
Carcinoma - non glandular malignant
Adenoma - glandular benign
Adenocarcinoma - glandular malignant
State some classes of carcinogens
- agents capable of causing cancer
1) Chemicals - e.g. paints, dues, rubber, soot. (most require metabolic conversion from pro-carcinogen to ultimate carcinogens)
2) Viruses - e.g. HPV (cervical cancer), EBV (burkitt lymphoma) - causes 10-15% of cancer
3) Ionising + non-ionising radiation - UVB (or UVA) (skin cancer) - basal cell carcinoma, squamous cell carcinoma (increased risk of xeroderma pigmentosum)
4) Hormones, parasites, mycotoxins - mycotoxins can be found in food/fungi/mold (aflatoxin - hepatocellular carcinoma)
5) Asbestos (fibrous minerals that are microscopic and can be inhaled)
What are dendritic cells and what is their origination?
Dendritic cell - Antigen presenting cells that initiate the adaptive immune response.
They are mesenchymal in origin and not hematopoietic.
What are primary and secondary lymphoid organs (name some examples)?
Primary –> Where immune cells originate, mature or develop
- Bone marrow (all cells originate here including T cells) - B cells mature here
- Thymus - development and maturation of T cells (thymic tolerance)
Secondary –> Where immune responses are initiated and coordinated
- Lymph nodes - antigen presenting cells and T/B cell interactions –> filters lymphatic fluid allowing immune cells to encounter and respond to antigens
- Spleen - RBC recycling, bacteria killing - it has lymphocytes and macrophages which can respond to infections
What is thymic tolerance and where does it occur?
A critical process that occurs in the thymus where T cells are developed to recognise and respond to foreign antigens while remaining tolerant to the body’s own tissues thus preventing autoimmune reactions. (T cell selection)
Positive selection - If the T cells recognise the thymus Major histocompatibility complexes (MHCs 1 and 2), then they are selected for
Negative selection - If the T cells produce an immune response (by recognising self antigens as foreign, they are selected against.)
Cytokines secreted by T helper cells 1 and 2
1 - interferon gamma - activates NKC and marcophages
helper cell 2 - interleukin 4,5,,,10 - activates b cells to differentiate into plasma cells
Examples of Type 1,2,3,4 hypersensitivity reactions
1 - Anaphylaxis, hay fever, allergies
2- Blood transfusion reactions, graves, hashimoto’s thyroiditis, good pasture’s, guillain barre, lambert eaton
3 - Post strep glomerulonephritis, SLE, farmer’s lung, rheumatoid arthritis
4) TB, MS
What is a naive T cell?
A T cell that has not encountered an antigen or has not matured
3 differences between innate and adaptive immunity
Innate - non specific, rapid response with no memory
Adaptive- specific, slow response with memory involved
Innate - Neutrophils and macrophages primarily involved
Adaptive - T cells and B cells are primarily involved
Innate - Killing via complement system
Adaptive - Killing is antibody mediated
What are symptoms that may present with anaphylactic shock (an acute medical emergency)?
- Severe hypotension
- Tachycardia + dyspnoea
- Pale
- Cold extremities
- Puffed up face + tongue
- Itching
- Urticaria (Hives)
- Central cyanosis (lips are blue)
