Pathology Flashcards
What are sequelae?
The range of possible outcomes of a disease.
What does pathogenesis mean?
The sequence of events between the healthy and clinical disease.
What mutation is associated with lung cancer?
Ki ras.
What mutation is associated with breast cancer?
Her2
What are Kochs postulates?
Four criteria designed to establish a causative relationship between a microbe and a disease.
What is apoptosis?
Programmed cell death.
What is P53?
A dna repair protein, when this is lost cancer can start as cells are allowed to proliferate unchecked.
What is a free radical?
An atom or molecule with unpaired valence electrons or an open electron shell making them highly chemically reactive. The molecules can spontaneously dimerise or polymerise upon contact.
What is a particularly important free radical to be aware of?
O2 - superoxide.
What does superoxide do? And how is it used?
Starts a chain reaction leading to lipid peroxidation.
What is a transgenic model?
An animal study.
What is superoxide normally used for in the body?
Biologically toxic and used by immune cells to kill invaders in an oxygen dependent mechanism.
What enzyme produces superoxide and on what type of cell?
NADPH oxidase in phagocytes.
What is chronic granulatomatous disease?
A mutation in the gene coding for NADPH oxidase. Characterised by extreme susceptibility to infection.
What is SOD?
Superoxide dismutase. A superoxide scavenging enzyme. Nearly all organisms living near oxygen contain isoforms of it.
Name a molecule with weak SOD activity and what does this mean?
Hb. Means it can easily be reduced and oxidised by superoxide.
What does an antioxidant do?
Molecule that inhibits the oxidation of other molecules.
Name a few free radicals?
Paracetamol, repercussion injury, inflammation and intracellular killing of bacteria etc.
What is reperfusion injury?
Tissue damaged that arises when blood supply returns to a tissue after a period of ischaemia. The absence of oxygen and nutrients from the blood during the ischaemic period creates a condition where the return of circulation results in inflammation and oxidative stress.
What factors affect the severity of a tissue injury?
Duration, nature, proportion of cells affected, regenerative capacity and topography.
What is hydropic change?
Also called vacuolar degeneration. Cellular swelling with microscopic small vacuoles seen within the cytoplasm which are distended and pinched of parts of the ER. It is a pattern of non lethal injury.
What are examples of non lethal tissue injury?
Hydropic change, fatty change (cells unable to metabolise fat, which are seen as vacuoles in the cytoplasm) and membrane shedding.
What is necrosis?
Pathological death of tissues. It elicits adjacent tissue response. If enough viable cells are around then regeneration may be possible.
What are the two types of cell death?
Apoptosis and necrosis.
What are the 6 different types of necrosis?
Caseous, fat, colliquative, coagulative, gangrenous and fibrinoid.
What is coagulative necrosis?
Accidental cell death from ischaemia or infarction. Cells look ghostly under microscopy as the architecture of the dead cell is maintained for a few days.
What is colliquative necrosis?
Otherwise called liquefactive necrosis. Digestion of dead cells form a liquid mass (pus). Typical of bacterial or fungal infections. Hypoxia brain injuries result in this due to high lipid and digestive enzymes in the tissues.
What is caseous necrosis?
Tissue maintains a cheese like appearance.
What is gangrenous necrosis?
Potentially life threatening condition where a large mass of tissue dies. Can be from injury, infection or chronic circulatory problems. Can be: dry, wet, gas, internal and necrotising fasciitis.
What is fibrinoid necrosis?
Form where an amorphous, basic proteinacious material accumulates in the tissue matrix. Looks like fibrin when stained. Can be caused by immune vasculitis, malignant hypertension and preeclampsia. Usually seen in immune reactions involving blood vessels.
What is fat necrosis?
Characterised by the action of enzymes in fat. Lipase releases fatty acids from triglycerides, this then joins with calcium to form soaps, giving chalky deposits. Usually associated with trauma of the pancreas. Can happen in the breast and salivary glands.
Describe inherited metabolic disorders?
Usually autosomal recessive. Cause a loss of function mutation.
How many people does PKU affect?
1 in 10000. Ireland 1 in 5000.
Describe PKU?
Autosomal recessive. Causes deficiency of phenylalanine hydroxylase leading to a build up of phenylalanine. Causes brain toxicity and retardation. Especially in growing brain. Children usually fair skin and blue eyed. Have Guthrie heel prick test at birth.
What are some of the harms of inflammation?
Mechanism of life threatening hypersensitivity reactions. Chronic inflammatory diseases e.g. Colitis. Fibrosis and disfiguring scars. Digestion of normal tissues, laryngeal oedema etc.
What is acute inflammation?
Initial and often transient reaction to tissue injury. Two phases: vascular phase (dilatation and increased permeability) and the exudate r and cellular phase (fluid and cells escape). Inflammatory response disrupts axial flow.
What is chronic inflammation?
Subsequent and often prolonged reaction following the initial response. Characterised by cellular reaction as opposed to time. Either develops from acute inflammation or is primary chronic inflammation.
What are the cardinal signs of inflammation?
Redness (rubor), pain (dolor), heat (calor), loss of function and swelling (tumor).
How do cell normally travel in a vessel?
Axial flow. Cells down the middle and plasma around the edges.
What features of vessels allow for vascular dilatation in acute inflammation?
Pre-capillary sphincters that are normally closed, meaning many of the capillaries lie empty, open allowing most capillaries to become full.
What is inflammatory fluid exudate comprised of?
Protein e.g. Immunoglobulin. Fibrinogen (turns to fibrin in contact with ECM. Exudate is continually being removed by the lymphatic system.
What are the steps in increased vascular permeability?
Brought about by chemical mediators including histamine and bradykinin. The leakage of fluid is confined to the post capillary venules. Endothelial cell contractile proteins contract and pull open transient pores which are largely intracellular. Endothelial cells are not damaged in the process.
What is the diagnostic feature of acute inflammation?
Neutrophils in the extra cellular space.
How does a neutrophil reach the site of an inflammatory stimulus?
Margination, adhesion and transendothelial migration.
Describe margination?
Loss of intravascular fluid makes blood more viscous allows disruption of axial flow as blood slows down and neutrophils can move into plasmatic zone (margination). Only occurs in venules.
Describe the steps in neutrophil adhesion?
In the resting state the neutrophil has surface selectin counter receptors and inactive integrins. When the neutrophil marginates the counter receptors adhere to selectin which is expressed in the surface of endothelial cells. This causes rolling adhesion. ICAM is then expressed on the endothelial cell which binds to the now activated integrins. This causes form adhesion and allows the transendothelial migration by the neutrophil inserting pseudopopia through the membrane.
What substances increase leukocyte surface adhesion molecule expression?
Complement C5a, leukotriene B4 and tumour necrosis factor (TNF).
What substances increase endothelial surface adhesion molecule expression?
IL-1, endotoxins and TNF.
What is chemotaxis?
Locomotion oriented along a chemical gradient. Is how leukocytes find antigens.
What compounds are chemotactic for neutrophils?
Bacterial products, complement proteins, cytokines and products produced by neutrophils themselves.
What does histamine do?
Vascular dilatation and transient increase in vascular permeability. Basically triggers vascular phase of inflammation.
What is histamine released by and what triggers it?
Mast cells, eosinophils, basophils and platelets. Release stimulated by: C3a, C5a and lysosomes proteins (neutrophils).
What are lysosomal compounds and what do they do?
Released from neutrophils. May increase vascular permeability and activate complement.
What is serotonin and what does it do?
5 hydroxytryptamine. Present in high concentration in platelets. Causes increased vascular permeability.
What are chemokines?
Proteins that attract various leukocytes to inflammatory site. Bind to extra cellular matrix components setting up a gradient for chemotaxis.
What are leukotrienes?
Synthesised from arachidonic acid, especially in neutrophils and have vasoactive properties. Involved in type 1 sensitivity reactions.
What 4 enzymatic cascade systems are in plasma?
Complement system, the kinins, coagulation factors and fibrinolytic system.
How are microorganisms recognised?
They become coated in opsonins. Which bind to receptors on leucocytes and enhance phagocytosis.
List some major opsonins.
Fc fragment of IgG, C3b complement protein and collectins (plasma proteins which bind to microbial cell walls.
What are the steps in phagocytosis?
Recognition, attachment, engulfment and phagolysosome formation. After this neutrophils undergo apoptosis.
What are the two variations of intracellular killing of microorganisms?
Oxygen dependent ( oxygen products do killing) and oxygen independent (lysosomes - attack bacterial coat or acidic pH inside phagocytic vacuoles).
What is suppuration?
Formation of pus. Causative stimulus almost always infective agent.
What is pus made of?
Neutrophils and bacteria/cellular debris.
What is an abcess?
Collection of pus surrounded by a membranes and sprouting capillaries, neutrophils and the occasional fibroblast. On draining the cavity collapses and is obliterated by organisation and fibrosis. Deep seated abscesses may drain along a sinus tract or fistula.
What are the benefits of acute inflammation?
Dilution of toxins and removal by lymphatics. Antibody migration, fibrin formation impeding microorganism movement, drug and nutrient transport and stimulation of the immune system.
What are the sequelae of acute inflammation?
Resolution or suppuration. Suppuration leading to discharge of pus and repair and organisation. This can then lead to fibrosis and chronic inflammation.
What are the cellular steps in acute inflammation?
Recognition, recruitment, removal and resolution.
What does resolution mean in relation to inflammation?
The complete restoration of the tissues to normal after and episode of acute inflammation.
What factors favour resolution?
Minimal cell death, regenerative capacity of organ, rapid destruction of causal agent and rapid removal of fluid and debris by vascular drainage.
What 3 things favour progression from acute to chronic inflammation?
- Indigestible substances (glass etc.) causing chronic suppuration (foreign body reaction)
- deep seated chronic suppuration with delayed drainage causes an abscess. Rigid walls can fail to come together after drainage, pus becomes organised and becomes fibrous scar.
- Recurrent episodes of acute inflammation and healing.
What is osteomyelitis?
Extremely difficult to eradicate chronic abscess.
What happens in chronic cholecystitis?
Replacement of wall by fibrous tissue. Lymphocytes rather than neutrophils predominate.
What are the predominant cells of chronic inflammation?
Lymphocytes, plasma cells and macrophages. Usually accompanied by granulation tissue resulting in fibrosis. May be a few eosinophils but neutrophils are scarce.
What are some examples of primary chronic inflammation?
Infective agent resistance to phagocytosis and intracellular killing e.g. tb, leprosy and viral infection.
Foreign body reaction to exogenous material e.g. Gout and UC.
Primary granulomatous disease (sarcoidosis).
What is the macroscopic appearance of chronic inflammation?
A chronic ulcer - that has breached the mucosa, has a base lined by granulation tissue and the fibrous tissue extends through the muscle layers.
A chronic abcess.
Thickening of the wall of a hollow viscous by fibrous tissue.
Granulomatous inflammation.
Fibrosis - may be the most prominent feature after cell infiltrate has subsided.
What are examples of chronic abcesses?
Osteomyelitis and empyema.
How does a monocyte mature?
In the bone marrow it goes from a stem cell to a promonocyte and then a monocyte in the blood. Then a macrophage in the tissues.
What is the name of a liver macrophage?
Kupfer cell.
What is the name of a lung macrophage?
Alveolar macrophage.
What is the name of a connective tissue macrophage?
Histiocyte.
What is the name of a bone macrophage?
Osteoclast.
What is a mass formed by several distinct cells, mostly macrophages?
Giant cell.
What do macrophages do and when are they apparent?
Appear late in the acute inflammatory response.
Responsible for clearing tissue debris and produce a range of important cytokines.
Which is more phagocytic a macrophage or a neutrophil?
Neutrophil.
What is a granuloma?
Aggregate of epithelioid histocytes.
What do histocytes do?
They have little phagocytic ability but a secretory function.
What is one of the main causes of granulomatous inflammation?
Indigestible materials.
What may augment granulomas?
Caseous necrosis or hystocytic giant cells.
What can cause granulomatous disease?
Specific infections, endogenous or exogenous foreign material, drugs or unknown e.g. Crohns or sarcoidosis.
Name two angiogenesis factors?
vEGF and PDGF.
What populations do cells divide into and can they be replaced?
Labile, stable or permanent - only the first two are replaceable.
What is healing?
Restitution with no or minimal residual effects.
In what type of injuries does healing by connective tissue fibrosis occur?
When Tissue destruction includes loss of parenchymal cells and stromal framework. the non regenerated parenchymal cells are replaced by connective tissue which in time produces fibrosis and scarring.
What are the four steps in repair by connective tissue fibrosis?
- Angiogenesis.
2-3. Fibrosis - Tissue remodelling/organisation.
Describe angiogenesis.
Basement membrane degradation of the parent vessel.
Migration of endothelial cells towards the angiogenic stimulus.
Endothelial cells proliferate and mature. Central growth inflammation remodels the cells into tubes.
Supportive cells are recruited e.g. Vascular smooth muscle.
Describe fibrosis?
Consists of emigration and proliferation of fibroblasts and deposition of ECM by these cells.
Collagen synthesis starts after this, the amount depends on the wound size.
Where does fibrosis occur, during connective tissue repair?
Within the granulation tissue framework of new vessels and a loose ECM.
What happens during tissue remodelling and organisation?
Granulation tissue is turned into a scar.
The composition of the ECM changes.
Metalloproteinases degrade collagen and other proteins.
The connective tissue framework is remodelled.
Organised are always appears firmer, shrunken and puckered.
What is an ulcer?
Local defect or excavation that is produced by sloughing of inflammatory necrotic tissue.
What secretes collagen?
Fibroblasts and leukocytes.
What wounds are healed by first intention?
Incisional wounds with opposed edges. There is limited cell death but the basement membrane is disrupted.