week 4 MOD Flashcards
what is inflammation and what is its purpose?
What can be the complications of inflammation?
it is a protective process involving host cells, blood vessels and proteins.
It removes the cause of the injury, removes necrosis because of the injury and iniates repair
It can damage nearby tisssue and be destructive
Can be inappropiate –> chronic inflammatory disease and autoimmune disease
what cell types are involved in chronic and acute inflammation?
What is the level of damage caused by chronic and acute inflammation?
acute –> neutrophils
chronic –> lymphocytes and macrophages
Acute –> mild/ self limiting tissue injury
Chronic –> severe prognosis
what is the time of onset of acute and chronic inflammation?
What are the signs of acute and chronic inflammation?
Chronic –> days to weeks
Acute –> mins to hours
Chronic –> subtle signs
Acute –> prominent signs
Are the same cells involved in chronic and acute inflammation what are they?
What other process occurs in chronic inflammation?
Chronic inflammation contains different cellular types such as plasma cells, lymphocytes and macrophages
There is a greater amount of granulation and scar tissue in chronic inflammation?
what is the process and out of acute inflammation?
The vessels dilate and leakage occurs of protein rich exudate.
Outcome is: resolution, supporation (abscess/pus formation), organisation or lead to chronic inflammation
Is chronic inflammation a primary or secondary cause?
It is usually primary but can be sequential after acute.
what is pernicious anaemia?
it is a autoimmune disease where the own body produced autoantibodies against intrinsic factors and gastric parietal cells –> no B12 produced and causes aneamia
what is Primary granulomatous ?
granulomas (collections of inflammatory cells) collect in organs, often lungs and lymph nodes, viewed as an immune reaction to usually an infection
How does suppurative acute inflammation develop to chronic inflammation?
supporative acute inflammation –> build up of pus –> which forms a abscess if deep enough wall thickens –> granulation and fibrosis allows a cavity to be produced where recurrent pus formation can be held. Recurrent acute inflammations leads to chronic such as cholecystitis
what is cholecystitis ?
The body immune system will go and fight the acute inflammation of the gall bladder.
But will keep recurring because the presents of stones
This will causes thickening of the muscle walls of the gall bladder and eventually chronic fibrosis of the gall bladder
Predominant cell type becomes lymphocyte rather than neutrophil polymorph
what occurs micrscopically in chronic inflammation?
Cellular infiltrate of lymphocytes, plasma cells and macrophages
Exudation if fluid is NOT prominent
Production of new fibrous tissue from granulation tissue
what are the 2 lymphocytes involved in chronic inflammation and what do they do?
B cells turn into plasma cells and produce antibodies
T cells produce cytokines
what is the result of cytokine release in chronic inflammation?
causes the attraction of macrophages which leads to the trapping of macrophage and the activation of macrophage –> phagocytosis
neutrophils get attracted and they release histamine which increases the vascular permeability
Cause perforins to kill invading cellsa and also the releae of interferons to activate NK cells and macrophages
what cells are found in the connective tissues?
Macrophages
Mast cells –> release histamine
FIbroblast cells –> structural proteins such as collagen
what cells types are found in the blood vessel during chronic inflammation?
Polymorphonuclear leukocytes (granulocytes), basophils, eosinophils, lymphocytes, plateletes, and monocytes
What is the role of macrophages in chronic inflammation?
Very important role, increase inflammation and activation of the immue system. At sight of damag which release cytokines which activates monocytes and they flow from the blood to the sight of infection –> Leukocyte extravasatio.
Proliferation of macrophages occur and they immobolise to deal with the infection–> cause tissue damage to due phagocytosis of bacteria and damaged tissue
Release protesase to debride damaged tissue
what is granulation tissue and what does it contain?
What is the aim of wound healing?
Is new connective tissue and blood vessels that have grown from the wound base.
Contains collagen from fibroblasts, inflammatory cells, macrophages and angiogensis occurs
Aim is to repair by replacement of injured tissues by fibrous tissues
why are macrophages important in the formation of granulation tissue in chronic inflammation?
Due to the low oxygen content stimulate them to produce factors to initiate angiogensis
Induce cells to re epithelialize wound and create granulation tissue
what is fibrosis?
What is the role of macrophages in fibrosis?
the formation of excess fibrous connect tissue during repaired of tissue damage
Macrophages initiates the laying down of connective tissue including collagen
what is fibroma?
it is when fibrous conenctive tissue is dervived from 1 abnormal cell that can cause a benign fibrous tumor of connective tissue
what is granulomatous inflammation?
Why is granulomas formed?
it is the build up of immune system cells known as histocytes
Granulomas is formed when the immune system tried to wall of a substance it percieves to be foreign but cannot eliminate it
what is granuloma?
is the aggregation (nodule) of epithelioid histiocytes and other cells; lymphocytes and histiocytic giant cells.
what is a characteristic of histocytes?
they have eosinophilic cytoplasm –> red/pink in colour and also have multiple nuclie
what is histiocytes?
stationary phagocytic cell in connective tissue –>
They form clusters with very little phagocytic activity.
However they produce angiotensin converting enzymes.
what is Histiocytic giant cell types?
Langhans giant cells = horseshoe arrangement of peripheral nuclei, seen in TB often.
Give examples of Granulomatous disease?
TB and leprosy
what is foreign body giant cells?
are large cells with randomly scattered nuclei in relation to the foreign body material
when is histiocytic giant cells formed?
Many of the stimuli that induce granulomatous inflammation are indigestible to macrophage and consequently histocytesa re formed. For example tubercle bacilli which has cell walls resistant to macrophages.
what is the structure of histiocytic giant cells formed due to tubercle bacilli?
multiple nuleis, formed when more than 2 macrophages try to digest the same thing and have no known function
give examples of bacterial granulomatous disease?
TB –> cough, haemoptysis, night sweats
Leprsosy –> m.leprae nerve granulomas, loss of pain sensation and injury. Also affects respiratory system and eyes and skin –> no to autoamputation
what is example of parastitic granulomatous disease?
schistosomiasis –> worms –> cause urinary tract/GIt –> haematuria, pain and diarrhoea
what is fungal granulomatous disease?
it is caused by being immunocompressed such as in HIV or taking autoimmune drugs –> cryptococcus
what type of disease is crohn’s disease?
granulomatous disease
what synthetic material causeses granulomatous disease?
silicoisis –> occupational disease, scarring and granuloma in lungs
what is Silicosis?
lung fibrosis caused by the inhalation of dust containing silica.
what occurs in stage 1 and 2 of the tb mechanism?
in week 1 –> Tb is inhaled into the lungs and invades the alveolar macrophages via the macrophage mannose receptor –> phagocytosis occurs and the bacteria multiplies inside
Stage 2 –> week 2 and 3 –> exponential proliferation of TB and the macrophage can no longer contain it
what is stage 3 of tb mechanism?
after week 3 –> phagocytosis and proliferation is balance in about 90% this is where it stops and get no signs or symptoms. Round complex is formed with TB and infected macrophage in the middle and normal macrophage surrounding. Tb can survive for years but not contagious and immune system can deal with it and leave a scar
what is stage 4 of Tb mechanism?
occurs only in about 4/5% of people and usually with people with immunocomprimised immunity –> such as people with HIV. Reactivation occurs 12-24 months later –> proliferation and cavity formed away from immune cells. Contagious
what is the involvement of chronic inflammation in MI?
Chronic inflammation occurs in myocardial infarction where the macrophages will cause the proliferation of fibroblasts.
Will get myocardial fibrosis where the heart muscle does not work properly leading to heart failure and arrythmias
what is MS inflammation?
plasma cells and T lymphocytes are seen in white matter where macrophages break down myelin
what is the role of inflammation in antheroma formation?
the macrophage adhere to the epithelium and recruit other cells to process the lipids that accumulate to plaques –> cause a block
what is H pylori infection?
production of proteases which damage the intestinal lining –> gastritis –> loss of protective barrier. Enzymes access the stomach wall and eventually perforation
what type of healing occurs when tissues can regrow?
healing by regeneration. Damaged cells are replaced by like and the tissue return back to normal –> the return of specialised function
what type of healing occrus when tissues cannot regrow?
healing by repair –> damaged cells cannot be replaced by like and fibrosis and scaring occurs –> loss of specialised function
give example of labile cell population and there characterstic?
epithelia –> very high turn over rate. Constantly shredding and production of new cells. Excellent regeneration capacity
large amount of stem cells in the epithelia they are in the basal part. Huge amount of cell proliferation
give examples of Stable (quiescent) cell populations and there characterstic?
example is liver and renal tubules. They have a physiological low turn over but they can drammatically increase there turn over rate if need be. Good regenerative capacity
what type of cell population is muscle cells and neurones? What are there characteristic.
permnant cell population. No physiological turn over. They have long cell life and no regeneration capacity.
give a summary of the cirrhotic of the liver?
long term continous damage of noxious agents –> leeds to the collapse of reticulin (connective tissue) framework of the liver and therefore regeneration of liver cells cannnot repopulate the normal architecture –. leeds to to the formation of regenerative nodules divided by fibrous septa.
give a few characterstics of stem cells?
Prolonged self-renewal
Asymmetric replication
Reservoirs present in many adult tissues (‘Adult’stem cell ‘niches’)
Give examples of destruction which can damage the stem cells
full thickness burns –> get very deep and damage the stem cells so they cannot produe the cells needed to form new skin (epithelia)
Radation
Survival of stem cells is crucial for regeneration
why can’t some cells regenerate?
lack of stem cell or damage to stem cell niche
what is the scaring of tissue made up of?
non specialised fibrous tissue
what is the process of rapair of tissue?
new capillary loops form around the dead tissue proliferate and grow into the dead tissue from the borders of it. Phagocytes such as neutrophils and macrophages come and eat up the dead tissues. There is proliferation and migration of myofibroblasts –> will lead to synthesis of collagen and ECM.
Acquire myofibrils and contractile ability. –> wound contracts
what occurs with the maturity of granuloma tissue?
Their vascularity and the cellular composition reduces dramatically. While the amount of ECM and collagen increase –> wound strength increases around 3 months
what local factors inhibit healing?
Haematome –>a solid swelling of clotted blood within the tissues.
blood supply –> diabetes small and large blood vessels cause variation in blood supply
mechanical stress
foreign bodies and infection
what are the systematic factors inhibiting healing?
Age –> child regenerates a lot quicker than older people
Drugs (eg steroids) –> drugs that causes the increase of catabolic states –> breaking down proteins more and therefore harder to heal
Anaemia
Diabetes –>both large and small vessel disease peripheral wounds don’t tend to heal very well restriction of blood supply and metabolic deficit
Malnutrition
Catabolic states
Vitamin C deficiency –> need for collagen synthesis
Trace metal deficiency
Why are the edges of a wound unable to be apposed in second intention healing?
Also what is the different between primary and secondary intention healing?
Wound edges not apposed Extensive loss of tissue Apposition not physically possible Large haematoma Infection Foreign body
The difference between primary and secondary:
Not a fundamentally different process
More florid granulation tissue reaction (“leaving a wound to granulate”)
More extensive scarring
By what week/day to you take Sutures out?
1 week –> 10% wound strength
what is haematoma
a solid swelling of clotted blood within the tissues.
what is the remodelling process when a bone is fractured?
Fractured healing
When a bone is broken you get a large haematoma at fracture site –
Removal of necrotic fragments by phagocytic cells –
Osteoblasts lay down woven bone leading to the formation of a callus at the fracture site –
Get remodelling according to mechanical stress –
Get replacement of woven bone by lamellar bone
Give reasons for non union fractures?
Misalignment
Movement –> if the two parts of the bone are two far apart after fracture then realignment cannot occur.
Infection –> soft tissue at end of bones
Interposed soft tissue
Pre-existing bone pathology= ‘pathological fracture’–>cancer in the bone can get a spontaneous fracture and also no osteoblasts to lay down the woven bone etc
what cell types are not in the brain and what are they replaced by?
Collagen and fibroblasts is not contained within the brain instead it is replaced by glial cells
what occurs when there is damage to brain tissue?
Macrophages remove the dead tissue and then have a cysts which is surrounded by reactive gliosis
Gliosis rather than scarring which is proliferation of astrocytes, a type of glial cell
what cells does tumour necrosis factor come from and what do they do?
TNF from T cells, mast cells and macrophages.
Activates macrophages; regulates other cytokines; multiple functions
what is organisation?
Repair of specialised tissue by formation of fibrous scar
What are the 7 growth factors which are involved in the control of healing?
1) Epidermal growth factor alpha 2) Transforming growth factor beta 3) Platelet-derived growth factor 4) Keratinocyte growth factor 5) Tumour necrosis factor 6) Vascular endothelial cell growth factors 7) Transforming growth factor alpha
What are the different causes of primary chronic inflammation? Give examples of each
Some infections –> TB, leprosy
Endogenous material–> necrotic adipose tissue
Exogenous material –> asbestos or prosthetics
Some autoimmune disease –> Rheumatoid arthritis, SLE and pernicious anaemia
Primary granulomatous disease –> Chrons
What are the morphological features of chronic inflammation?
Infiltration of mononuclear cells (plasma cells, lymphocytes and macrophages)
Tissue destruction
Healing by fibrosis
What is the macrosopic feature of chronic peptic ulcer?
Breaching of the mucosal
Granulation tissue at the base
Fibrosis through out the wall
What is a marker for chrons disease?
Granuloma
What are the main macroscopic features of chronic inflammation?5
Chronic ulcer Chronic abscess cavity Thickening of the wall Granulomatous Fibrosis
What are the features of epitheloid histocytes?
Have a large vesicular nuclei and eosinophilic cytoplasm –> stain pink/red and have large nucleus
In early granuloma what cells does it contain? What does it develop into?
Contains lymphocytes and macrophages
Develops either into caseating or noncaseating epitheliod granuloma
What is the role of macrophages in antheroma formation?
Adhere to the endothelial lining causing accumulation of other cells and process lipids
What structures in the body have limited architertural regrowth?
Glomeruli and lungs
What factors control regeneration?
Stem cell proliferation rate or amplification of stem cells
The covering of the defect
Complex control by growth factors, cell to cell and cell to matrix interaction
Contact inhibition
How does healing occur in first intentios?
1) You will get an area of clot forming between the edges - dont want a haematoma, just get a small fibrinous clot - 24 hours 2) 3-7 days, phagocytic cells remove fibrinous clot and organisation begins 3) Weeks - epithelia forms and get a small scar
What type of cut will heal by first intentions?
Clean uninfected surgical wound
Good haemostasis
Edges are apposed e.g with staple or stitches
Why is it important that cytokines tightly control healing?
They prevent neoplasia from occuring and that is why they are of interest in cancer therapy