Mechanisms Of Disease (S1-7) Flashcards
S2: Cellular Injury S3: Acute Inflammation S4: Chronic Inflammation S5: Regeneration And Repair S6: Haemostasis, Thrombosis And Embolism
How can changes in environmental factors lead to changes in the cell? (S2)
A cell will show adaptations initially, such as shrinking. As the environmental conditions become more severe and less favourable, cellular injury and ultimately death may result
What three factors determines the severity of cellular injury? (S2)
The type of injury, the severity of injury and the type of tissue.
Name three causes of cellular injury and death. (S2)
Hypoxia, toxins and immune mechanisms… AND physical agents - such as physical trauma, extreme changes in temperature, pressure; radiation; micro-organisms and dietary deficiencies or insufficiency / excess
What is hypoxia? How does it differ from ischaemia? (S2)
Hypoxia is where there is oxygen deprivation to tissues of the body. Ischaemia is where there is no supply of blood to a part of the body.
Why is ischaemia more dangerous than hypoxia? (S2)
Ischaemia not only deprives part of the body of oxygen, but also of other important substrates such as glucose. It can be the result of a major blood clot or hypotension.
What will happen to hypoxic cells? (S2)
Initially they may show adaptations such as shrinkage, but over time cellular injury and ultimately death will result.
What are the 4 ways hypoxia can be classified? Give a brief explanation of each one and a couple of examples. (S2)
Hypoxaemic hypoxia - low arterial concentration of O2, reduced pO2 at altitude, or secondary to lung disease.
Anaemic hypoxia - decreased ability of Hb to carry oxygen… anaemia, CO poisoning
Ischaemic hypoxia - interruption to blood supply… blockage of a vessel, heart failure
Histiocytic hypoxia - inability for cells to utilise oxygen due to disabled enzymes which are utilised in oxidative phosphorylation… cyanide.
How sensitive are neurones to hypoxia? And fibroblasts? (S2)
Neurones will die within a few minutes whereas fibroblasts in the dermis of the skin can last up to a day without oxygen.
Why can O2 be a toxin? (S2)
Everyone has a baseline oxygen saturation. If, in ICU, we put someone who came in with a normal O2 sat of 90% on 100% several problems can occur such as the formation of reactive oxidative species! They are normally single oxygen atoms with one electron missing. They can damage nucleic acids and therefore be mutagenic.
Name a handful of toxins bar the controversial O2. (S2)
Medicines e.g. chemotherapy, asbestos, alcohol… AND poisons, pollutants, pesticides/herbicides, narcotic drugs
What are the two methods of immune mechanisms that can cause harm to cells? (S2)
Hypersensitivity reaction - here the host tissue is injured secondary to an overly vigorous immune reaction - seen in urticarial (hives), inflammation of the skin
Autoimmune reactions - immune system fails to differentiate between self and non-self - seen in Grave’s disease.
Briefly outline the process of Grave’s disease (S2)
Antibodies are secreted which stimulate the TSH receptors on follicle cells resulting in increased production and release of T3 and T4.
What are the four cell components that are principal targets of cell injury? (S2)
Cell membranes, nucleus, proteins and mitochondria.
When there is hypoxia, cells produce less ATP by oxidative phosphorylation. At what levels (of ATP) do vital cellular functions become compromised? (S2)
5-10%
When there is hypoxia, what is the first thing to go when ATP is depleted? (S2)
The Na+-pump which maintains the gradient between the inside and the outside of the cell (it is energy dependent).
When there is hypoxia, what other things will happen? Are these reversible? (S2)
Oncosis –> Sodium and calcium start to rush in to the cell and water follows it.
Anaerobic respiration –> this leads to the build-up of lactic acid. It affects the cell’s enzymes and leads to the nucleus’s chromatin clumping and becoming abnormal. Reduced protein synthesis –> The ribosomes need energy to stick to the endoplasmic reticulum, therefore – when there is less ATP – protein synthesis is reduced, this effects cellular metabolism.
Yes they are reversible.
Why is a high intracellular calcium bad? (S2)
Calcium, a very biologically active substance, is normally locked away in the endoplasmic reticulum and the mitochondria. When it is in the cytoplasm, it activates many enzymes, which is not what we want.
When may cellular injury from hypoxia become irreversible? (S2)
Probably when calcium enters the cytoplasm. It activates ATPase (which breaks down ATP to ADP), phospholipase (breaks down cell membrane), protease (breaks down proteins in cell membrane) and endonucleases (breaks down DNA).
What is ischaemia-reperfusion injury and why can the reperfusion cause injury? (S2)
Ischaemia-reperfusion injury is where blood flow is returned to a tissue previously subjected to ischaemia. The restoration of blood flow can cause injury due to:
Increased production of oxygen free radicals
Increased neutrophils after blood flow returns, resulting in more inflammation and increased tissue injury.
Delivery of complement proteins and activation of the complement pathway.
What are free radicals? (S2)
They are reactive oxygen species - a single oxygen with one electron missing and are often produced through ischaemia-reperfusion injury and cellular ageing. They damage nucleic acids and can therefore be mutagenic.
What are some of the useful functions of free radicals? (S2)
They are produced by leucocytes in the body and are involved in killing bacteria. They are also used in cell signalling.
Name some ROS, which is the most dangerous? (S2)
OH.. ; O2- ; H2O2. OH.. is the most dangerous.
How can OH.. be formed? (S2)
Radiation directly lysing water, giving OH..
Through the Fenton and Haber-Weiss reactions: H2O2 and O2- are substrates which explains why we seek to rapidly remove these if they are present in the body.
What are the two defence systems of the body to prevent injury caused by free radicals? (S2)
The anti-oxidant system and the utilisation of heat shock proteins.
What is oxidative stress? (S2)
Oxidative stress is when there is an imbalance between free radical production and free radical scavenging leading to free radicals building up in the cell or tissue, causing cellular injury.
What are free radical scavengers? (S2)
Examples include vitamin A, C and E as well as glutathione. They neutralise free radicals.
What does the anti-oxidant system consist of? (S2)
- Enzymes: SOD (superoxide dismutase) catalyses the reaction O2- H2O2 which is significantly less toxic to cells. Catalases and peroxidases complete the process of free radical removal: H2O2 H2O + O2
- Free radical scavengers: …
- In the extracellular matrix, storage proteins (e.g. transferrin) sequester transition metals (e.g. iron and copper) which catalyse the formation of free radicals.
What are heat shock proteins? (S2)
They are important when the folding step in protein synthesis goes astray or when proteins denature due to cell injury. They ensure proteins re-fold correctly. If this is not possible the misfolded protein is destroyed.
In cells that are injured, what are the three main changes that can be seen with a light microscope? (S2)
- Cytoplasmic changes – reduced pink staining of cytoplasm due to accumulation of water (reversible). Increased pink staining may be present due to detachment and loss of ribosomes from the endoplasmic reticulum and accumulation of denatured proteins (irreversible).
- Nuclear changes – chromatin subtly clumped (reversible) may be followed by combinations of pyknosis (shrinkage), karryohexis (fragmentation) and karryolysis (dissolution) of the nucleus (irreversible).
- Abnormal intracellular accumulations (covered later)
In cells that are injured (but at a stage that is still REVERSIBLE), what can be observed under an electron microscope? (S2)
Swelling - due to Na+ pump failure.
Cytoplasmic blebs, symptomatic of cell swelling.
Clumped chromatin due to reduced pH.
Ribosomes dissociate from ER. This is because maintaining the ribosomes’ location is energy-dependent.
In cells that are injured (but at a stage that is IRREVERSIBLE), what can be observed under an electron microscope? (S2)
Further cell swelling
Combination of pyknosis, karryohexis and karryolysis.
Swelling and rupture of lysosomes – reflects membrane damage
Membrane defects
The appearance of myelin figures (which are damaged membranes)
Lysis of the ER due to membrane defects
Amorphous densities in swollen mitochondria
What is oncosis? (S2)
The spectrum of changes that occur in injured cells prior to death.
What is necrosis? (S2)
The morphologic changes that follow cell death in living tissue. This is largely due to the progressive degradative action of enzymes on a lethally injured cell.
What is apoptosis? (S2)
Self-induced cell death. A cell activates enzymes that degrade its own nuclear DNA and proteins.
Where is necrosis seen? (S2)
Necrosis is seen where there is damage to cell membranes (plasma and organelle). Lysosomal enzymes are released into the cytoplasm and digest the cell. Cell contents leak out of the cell and inflammation is often seen.
How long do necrotic changes take to develop? (S2)
Necrotic changes develop over a couple of hours. It takes 4-12 hours after a MI for microscopic changes to be seen.
How are necrotic cells removed? What will happen if they remain? (S2)
Necrotic cells are eventually removed by enzymatic degradation and phagocytosis (by white cells). Necrotic tissue that remains may calcify, known as dystrophic calcification.
The balance between two key processes determines whether coagulative or liquifactive necrosis is seen, what are these? (S2)
Enzymatic degradation and denaturation of protein.
If protein denaturation is the more dominant process (than enzymatic degradation) which type of necrosis will we see? (S2)
Coagulative necrosis. This occurs when the proteins tend to ‘clump’ leading to solidity of the dead cells and consequently of the dead tissue. In most solid organs, when cause of death is ischaemia, coagulation necrosis is common.
If cell death is associated with a lot of neutrophils, which type of necrosis might this be? (S2)
The neutrophils release proteolytic enzymes so it would be liquifactive.
Does the pancreas display coagulative or liquifactive necrosis? (S2)
The pancreas shows coagulative necrosis, but as it is rich in proteolytic enzymes (such as trypsin) the changes are modified to a certain extent.
In cells which have coagulative necrosis, histologically what would be seen? Would this change? (S2)
The cellular architecture is preserved creating a ‘ghost outline’ of the cells. These changes will only be seen in the first couple of days. Appearances will change because dead tissue incites an acute inflammatory reaction with infiltration by phagocytes.
Why is liquifactive necrosis seen in massive neutrophil infiltration (i.e. in abscesses)? When is liquifactive necrosis often seen? (S2)
This is because neutrophils release proteases. It is often seen in bacterial infections and is also seen in the brain (this is a fragile tissue without support from a collagenous matrix).
Why is caseous necrosis known in this way? (S2)
Caseous is Latin for cheese; caseous necrosis can have a cheesy appearance macroscopically.
What is caseous necrosis often associated with? (S2)
Infections, especially tuberculosis.
Histologically what characterises caseous necrosis? (S2)
Amorphous (sturctureless) debris, not ghost outlines as seen in coagulative necrosis.
Which form of inflammation is caseous necrosis often associated with? (S2)
Granulomatous.
When does fat necrosis occur and when is it typically observed? (S2)
Fat necrosis occurs when there is destruction of adipose tissue. It is typically seen as a consequence of acute pancreatitis. During inflammation of the pancreas there is a release of lipases from injured pancreatic acinar cells. The lipases act on the fatty tissue of the pancreas and on fat elsewhere in the abdominal cavity.
Clinically how could fat necrosis be observed? (S2)
Fat necrosis causes release of free fatty acids which can react with calcium to form chalky deposits (calcium soaps) in fatty tissues. These will be seen on x-ray and with the naked eye at surgery and autopsy.
What is gangrene? (S2)
Gangrene is not a type of necrosis, it is merely a term used to describe necrosis visible to the naked eye.
What type of necrosis causes ‘dry’ and ‘wet’ gangrene respectively? (S2)
It can be ‘dry’ if due to coagulative necrosis, or ‘wet’ if due to liquifactive necrosis.
Why is wet gangrene very serious? (S2)
Wet gangrene is very serious, it is typically due to infection and can result in septicaemia. Gangrene is most commonly seen in ischaemic limbs. It is dead tissue; it cannot be salvaged.
What is an infarction? (S2)
Infarction is a cause of necrosis, namely ischaemia. Infarction can result in gangrene and is often due to thrombosis or embolism. They can occasionally be due to external compression of a vessel or twisting of vessels.
What type of necrosis can be seen in infarcted tissue? (S2)
The necrosis in infarcted tissue can be coagulative or liquifactive, e.g. ischaemic necrosis in the heart (MI) shows coagulative necrosis; ischaemic necrosis in the brain (cerebral infarction) shows liquifactive necrosis.
Where does a white infarct occur? (S2)
A white (anaemic) infarct occurs in ‘solid’ organs (those with good stromal support) after occlusion of an end artery. White infarcts occur in the heart, spleen and kidneys.
What is an end artery? (S2)
AWhn artery that is the sole source of arterial blood to a segment of an organ
Why is a white infarct known as a white infarct? (S2)
In white infarcts, the solid nature of the tissue limits the amount of haemorrhage that can occur into the infarct from adjacent capillaries. The tissue supplied by the end artery dies and appears pale white because of a lack of blood in the tissue.
How would white infarcts appear? (S2)
Most are wedge-shaped with the occluded artery at the apex of the wedge. Histologically white infarcts appear as coagulative necrosis.
Where does a red infarct occur? (S2)
A red (haemorrhagic) infarct occurs where there is haemorrhage into dead tissues. This can be in the lungs or the intestines due to:
- In organs with dual blood supply, (e.g. the lung) occlusion of the main artery causes an INFARCT. The secondary artery is insufficient to rescue the tissue but allows blood to enter the dead tissue creating a RED infarct.
- If numerous anastomoses are present, (e.g. intestines). The reasons that is red are similar to 1..
- In loose tissue, (e.g. the lung) where there is poor stromal support for capillaries.
What do the consequences of the infarct depend on? (S2)
Is it an end artery?: whether the tissue affected has an alternative blood supply.
How quickly the ischaemia occurred? If slowly there is time for development of additional perfusion pathways.
How vulnerable a tissue is to hypoxia?
The O2 content of the blood? (an infarct in an anaemic patient may be more serious).
Is apoptosis a ‘normal’ process or does it only occur when cells are damaged? (S2)
It can be a normal physiological process occurring when cells which are no longer needed are removed to remain a steady state. It also occurs when a cell is damaged, particularly it’s DNA.
When is apoptosis seen? (S2)
This is seen during hormone-controlled involution and in cytotoxic T cell killing of virus-infected or neoplastic cells. It is also seen in embryogenesis.
How does apoptosis occur? (S2)
During apoptosis a cell activates enzymes that degrade its own nuclear DNA and proteins, however membrane integrity is maintained.
Does apoptosis require energy? (S2)
The process is energy-dependent.
How would apoptotic cells appear through a light microscope? (S2)
Apoptotic cells are shrunken and appear eosinophillic. There is chromatin condensation, pyknosis and nuclear fragmentation. If affects small cells or small clusters of cells.
How would apoptotic cells appear through an electon microscope? (S2)
Through an electron microscope apoptotic cells show cytoplasmic blebbing. This progresses to fragmentation into membrane-bound apoptotic bodies which contain cytoplasm, organelles and other nuclear fragments. The apoptotic bodies are eventually removed by macrophage phagocytosis.
Does apoptosis cause leakage of cell contents? (S2)
No leakage of cell contents occurs; apoptosis does not induce inflammation.
What are the key phases of apoptosis? (S2)
Apoptosis has three phases: Initiation, Execution and Degradation/Phagocytosis.
What are caspases and how do they act? (S2)
Apoptosis is triggered by two key mechanisms, intrinsic and extrinsic which both culminate in the activation of caspases. Caspases are proteases that mediate the cellular effects of apoptosis. They act by cleaving proteins breaking up the cytoskeleton and initiating the degradation of DNA.
Why is intrinsic apoptosis known so? (S2)
Intrinsic (mitochondrial) apoptosis has mitochondria as a central player. It is called intrinsic because all of the apoptotic machinery is within the cell.
What are a few of the triggers for intrinsic apoptosis? (S2)
DNA damage or withdrawal of growth factors or hormones. The triggers lead to increased mitochondrial permeability, resulting in the release of cytochrome c from mitochondria. This interacts with APAF 1 and caspase 9 to form an apoptosome that activates various downstream caspases.
What is the cause of extrinsic apoptosis? (S2)
Extrinsic (receptor-mediated) apoptosis is caused by external ligands such as TRAIL and Fas, that bind to ‘death receptors’.
Are mitochondria involved in extrinsic apoptosis? (S2)
No.
What happens during the degradation phase of apoptosis? (S2)
During the degradation phase of apoptosis the cell breaks into membrane bound bodies (apoptotic bodies). They express molecules on their surface that induce phagocytosis of the apoptotic bodies by either neighbouring cells or phagocytes.
What is p53? (S2)
It is the guardian of the genome, it mediates apoptosis in response to DNA damage.
What forms the apoptosome? (S2)
Cytochrome c, APAF 1, caspase 9: together are the apoptosome.
What does Bcl-2 do, what effect does this have? (S2)
Bcl-2 prevents cytochrome c release from the mitochondria, inhibiting apoptosis.
Give an example of a death ligand and a death receptor? (S2)
TRAIL, TRAIL-R
Are abnormal cellular accumulations toxic? (S2)
They can be, alternatively they can be harmless.
What can abnormal cellular accumulations consist of? (S2)
Normal cellular constituents, e.g. water, lipids, proteins..
Abnormal substances, exogenous: e.g. minerals; or endogenous: products of abnormal metabolism
Pigments
What are some examples of situations where there are abnormal cellular accumulations of lipids? (S2)
Steatosis and high cholesterol.
What is steatosis? (S2)
It is the accumulation of TAGs, often seen in the liver, the major organ of fat metabolism. Common causes of liver steatosis are alcohol abuse, diabetes mellitus, obesity and toxins (carbon tetrachloride). Mild steatosis doesn’t appear to have any effect on cell function.
Which cells can cholesterol accumulate in? What are they subsequently known as? (S2)
Cholesterol accumulates within smooth muscle cells and macrophages within atherosclerotic plaques. Cholesterol is also seen in macrophages within the skin and tendons of people with hyperlipidaemias. The macrophages form small masses called xanthomas. Microscopically these cells appear to have foamy cytoplasm – they are known as foam cells.
Histologically, how are abnormal cellular accumulations of proteins observed? (S2)
Proteins: seen as eosinophilic droplets or aggregates in the cytoplasm.
What are a couple of examples of abnormal cellular accumulation of protein? (S2)
Mallory’s hyaline is a damaged protein seen in hepatocytes in alcoholic liver disease. It is due to accumulation of altered keratin filaments.
In α1-antitrypsin deficieny, the liver produces a version of the protein α1-antitrypsin that is misfolded. This cannot be packaged by the ER and accumulates within this organelle; it is not secreted by the liver.
What would systemic deficiency in α1-antitrypsin result in? (S2)
Systemic deficiency in this enzyme means that proteases within the lung can act unchecked; the breakdown of lung tissue would result in emphysema.
What are examples of exogenous pigments that may accumulate in the cell? (S2)
Carbon/coal dust. Once inhaled it is phagocytosed by macrophages within lung tissue. It is seen as blackened lung tissue (anthracosis) or as blackened peribronchial lymph nodes. If particularly high exposure occurs (coal miners) the lungs can become fibrotic or emphysematous (coal worker’s pneumoconiosis).
Tattooing is another example. The pigments are phagocytosed by macrophages within the dermis which remain there indefinitely.
What are some examples of endogenous pigments that can accumulate in cells abnormally? (S2)
Lipofuscin: a brown pigment seen in ageing cells. A sign of previous free radical injury and lipid peroxidation.
Haemosiderin is derived from haemoglobin. It is yellow/brown and contains iron. It forms when there is systemic or local excess of iron.
Bilirubin is a bile pigment. It is deposited in tissues causing jaundice. It is often a result of haemolytic anaemia or abnormal liver function.
What is a common example of haemosiderin accumulation? (S2)
In the skin and subcutaneous tissues as a bruise. Haemosiderosis is seen in organs where there is a systemic overload of iron. It is seen in haemolytic anaemias, blood transfusions and hereditary haemochromatosis. When severe, liver, heart and pancreas damage can occur.
What is pathological calcification? (S2)
It is the abnormal deposition of calcium salts within tissues.
Pathological calcification can be either…? (S2)
Dystrophic or metastatic.
Where does dystrophic calcification occur?
Dystrophic calcification occurs in an area of dying tissue, in atherosclerotic plaques, in ageing or damaged heart valves (it can cause organ dysfunction, seen in the previous two sites) and in tuberculus lymph nodes.
With dystrophic calcification is there an abnormality in calcium metabolism or serum calcium concentration? (S2)
No.
What is metastatic calcification? (S2)
It is the abnormal deposition of calcium salt in normal tissues.
Why does metastatic calcification occur? (S2)
It occurs when there is hypercalcaemia which is secondary to disturbances in calcium metabolism. It is usually asymptomatic.
What are the four main causes of hypercalcaemia? (S2)
- Increased secretion of PTH resulting in bone resorption. This could be due to parathyroid tumours or ectopic secretion of PTH-related protein by malignant tumours
- Destruction of bone secondary to primary tumours of bone, such as leukaemia, Paget’s disease, metastases to bone or immobilisation.
- Vitamin D related disorders
- Renal failure.
What is replicative senescence? Why does it occur? (S2)
As cells get older, They experience replicative senescence, a decline in their ability to replicate until they eventually cannot. After a certain number of divisions cells eventually reach replicative senescence. This is related to the length of chromosomes: the chromosomes’ telomeres (located at the ends) shorten after each cellular division. When the telomeres reach a critical length the cell can no longer divide.
Where can telomerase be found? What does it do? (S2)
Germ and stem cells contain telomerase which maintains the original length of the telomeres. Many cancer cells produce telomerase and so have the ability to replicate multiple times.
How is alcohol metabolised? (S2)
Ethanol (the alcohol) is metabolised by alcohol dehydrogenase, the cytochrome p450 enzyme CYP2E1 and catalase to acetaldehyde. This is metabolised by aldehyde dehydrogenase to acetic acid.
Can cytochrome P450 enzyme CYP2E1 be induced? (S2)
Yes it can. This means metabolic tolerance of alcohol can be increased as well as that of other drugs catalysed by CYP2E1.
Woman have lower concentrations of aldehyde dehydrogenase, what does this mean? (S2)
Women can drink less alcohol than men, but have the same alcohol levels in their blood.
Why can ‘Asian flush’ be observed in those from the orient? (S2)
‘Asian flush’ occurs in 50% of those from the orient. They have reduced activity of aldehyde dehydrogenase – the subsequent build-up of aldehyde dehydrogenase results in facial flushing.
What are the three major changes alcohol can have on the liver? (S2)
Fatty change – alcohol toxicity causes steatosis of the liver, causing hepatomegaly. This is acute, reversible and generally asymptomatic.
Acute alcoholic hepatitis – a binge of alcohol can result in this with focal hepatocyte necrosis, the formation of Mallory bodies and a neutrophillic infiltrate. It can give symptoms of fever, liver tenderness and jaundice. It is usually reversible.
Cirrhosis – seen in 10-15% of alcoholics, resulting in a shrunken liver. Histologically appears as micronodules of regenerating hepatocytes surrounded by bands of collagen. Irreversible and sometimes fatal.
How is paracetamol detoxified? (S2)
Paracetamol is detoxified in the liver through glucuronidation and sulphonation. Small amounts are metabolised by cytochrome p450 oxidation (CYP2E1) to a highly toxic metabolite, NAPQI. Glutathione detoxifies NAPQI, but If a paracetamol overdose is taken glutathione would be depleted, and NAPQI accumulates.
How does NAPQI interact with the liver? (S2)
NAPQI binds with sulfhydryl groups on liver cell membranes, causing hepatocyte necrosis and liver failure. Massive liver necrosis occurs 3-5 days after a large paracetamol overdose.
Why are some people more susceptible to paracetamol overdose? Which groups of people are? (S2)
This is due to having lower reserves of glutathione. These include: those who took alcohol with the paracetamol, the alcohol-dependent, those who have AIDS or are HIV positive, malnourished and those on enzyme-inducing drugs, e.g. carbamazepine.
What is the antidote for paracetamol overdose? When should it be given? (S2)
N-acetylcysteine, which increases hepatic glutathione. To decide whether it is required, from 4 hours after the overdose the serum concentration of paracetamol is measured. The INR (or prothrombin time) measured 24 hours after the overdose is a guide to the severity of the liver damage in these patients.
What does aspirin do? (S2)
Acetylsalicylic acid or aspirin acetylates platelet cyclooxygenase and blocks platelets’ ability to make thromboxane A2, a substance which activates platelet aggregation.
What are the consequences of aspirin overdose? (S2)
Major consequences are metabolic. Aspirin stimulates the respiratory centre which results in respiratory alkalosis. Compensatory mechanisms result in metabolic acidosis. Aspirin (in overdose) results in an increase in lactate, pyruvate and ketone bodies contributing to the acidosis (this is due to the fact it interferes with carbohydrate, fat and protein metabolism as well as oxidative phosphorylation).
If there is aspirin overdose what may be present?
Petechaie (small red spots on the body caused by haemorrhages in capillaries): as platelet cyclooxygenase is inhibited there is decreased platelet aggregation reducing clotting. Acute erosive gastritis, leading to GI bleeding may be present.
What is inflammation? (S3)
Inflammation is the response of living tissue to injury. It is initiated to limit tissue damage.
There are vascular and cellular reactions (accumulation of fluid exudate and neutrophils in tissues); it is controlled by a variety of chemical mediators derived from plasma or cells; it is protective (but can lead to local complications and systemic effects.
What is acute inflammation? (S3)
Acute inflammation is innate, immediate and early; it is stereotyped. It has a short duration.
What are the causes of acute inflammation? (S3)
Microbial infections – e.g. pyogenic organisms Hypersensitivity reactions (acute phase) Physical agents Chemicals Tissue necrosis
What are the clinical signs of acute inflammation? (S3)
Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) and a loss of function.
What are the important tissue changes in acute inflammation? (S3)
- Changes in blood flow (vascular)
- Exudation of fluid into tissues
- Infiltration of inflammatory cells (cellular).
What happens following a tissue injury?
In order:
1. Transient vasoconstriction of arterioles (few seconds)
2. Vasodilation of arterioles and then capillaries leads to an increase in blood flow (rubor and calor are seen)
3. Increased permeability of blood vessels
exudation of protein-rich fluid into tissues
slowing of circulation (tumor)
4. Concentration of RBCs in small vessels and increased viscosity of blood = stasis.
What is histamine? (S3)
Histamine is a chemical mediator involved in the immediate early response of inflammation.
What is histamine released from and in response to? (S3)
It is released from mast cells, basophils and platelets in response to many stimuli, such as:
physical damage, immunologic reactions, C3a, C5a, IL-1 factors from neutrophils and platelets.
Which mediators are involved in a persistent response? (S3)
Examples include leukotrienes, bradykinin although there are many chemical mediators involved with a persistent response.
What is Starling’s Law? (S3)
Starling’s Law is that fluid flow across vessel walls is determined by the balance of hydrostatic and oncotic (colloid osmotic) pressure comparing plasma and interstitial fluid.
Under which situations would there be an increase in fluid flow out of the vessel? (S3)
When there is increased hydrostatic pressure or if there is increased oncotic (colloid osmotic) pressure (albumin) in the interstitium.
What is hydrostatic pressure? (S3)
From inside the capillaries, think of hydrostatic pressure as the ‘pushing force’, pushing the fluid out of the capillaries. It’s the result of the actual pressure of the fluid on the capillary walls.
