MoD Flashcards
What is infarction?
Tissue death caused by obstruction of the blood supply
What are some common causes of cell damage?
Hypoxia, immune mechanisms, toxins, trauma, radiation
What are the types of hypoxia?
Hypoxic - low O2 content of blood
Anaemic - decreased ability of Hb to carry O2
Ischaemic - Interruption to blood supply
Histiocytic - Inability of the cell to use O2
How do free radicals cause cellular damage?
Oxidise lipids of cel membrane and can cause DNA mutation
What is the function of heat shock proteins?
Refold damaged proteins
What are some reversible cell changes?
Reduced staining due to increased water content
Clumping of chromatin
Blebs
Accumulation of fat/keratin
What are some irreversible cell changes?
Nuclear changes
Damage to membranes
Lysosome rupture
Lysis of ER
What are the three types of irreversible cell changes?
Pyknosis, karyolysis, karyohexis
What is pyknosis?
Shrinking of nucleus
What is karyolysis?
Dissolution of nucleus
What is karyohexis?
Fragmentation of nucleus
What are the types of necrosis?
Coagulative, liquefactive, caseous and fat
What is coagulative necrosis - where does this commonly occur?
Necrosis whereby dead tissue has a solid consistency with a ghost outline. Occurs when protein denaturation is the dominant process, in cases of ischaemia. Commonly occurs in the kidney or heart
What is liquefactive necrosis?
Necrosis whereby tissues are digested leading to digestion of tissues. Occurs when the dominant process is release of enzymes. Seen in the brain and the lungs
What is the cause of caseous necrosis?
Infections such as TB
What is the cause of fat necrosis?
Pancreatitis and trauma
What is gangrene?
Necrosis that is visible to the naked eye
What is a white infarct?
An infarct that occurs after the occlusion of an end artery - so the tissue has no blood supply
What is a red infarct
An infarct that occurs in a tissue with a dual blood supply - some blood is present but not enough to sustain the tissue
How is apoptosis initiated?
Internal pathway - internal changes such as DNA damage
External pathway - external changes - receptor mediated
How is apoptosis executed?
Intrinsic - increased membrane permeability results in release of cytochrome C which interacts with APAF1 gene and caspase 9 protein to form an apoptosome. The apoptosome activates a series of enzymes
Extrinsic - A death ligand such as TRAIL binds to a death receptor resulting in caspase activation
Apoptosis - degradation
Caspase breaks down the cell into membrane bound fragments which can be broken down by phagocytes or taken up by neighbouring cells
What is p53?
A protein which mediates apoptosis in response to DNA damage, suppressing tumours. It is described as the guardian of the cell
What are some key differences between apoptosis and necrosis?
Apoptosis affects single cells, shrinkage occurs, the plasma membrane remains intact, no adjacent inflammation
What are some consequences of chronic alcohol intake?
Raised AST/ALT levels Alcoholic hepatitis - elevated serum bilirubin and jaundice cirrhosis cardiomyopathy gastritis/pancreatitis growth/mental retardation of children Birth defects
What is the treatment for a paracetemol overdose
Measure serum paracetemol levels to decide whether to administer n-acetylcysteine
What occurs in an aspirin overdose?
Respiratory alkolosis followed by respiratory acidosis
GI bleed and gastritis
petechaie - red spots caused by haemorrhage
What are the common symptoms of acute inflammation?
Calor - heat Dolor - pain Rubor - redness tumour - swelling loss of function
What are some common causes of acute inflammation?
Infection, chemicals, tissue necrosis, hypersensitivity reactions, trauma
What is the general progression of acute inflammation?
Changes in blood flow > exudation of fluid > infiltration of inflammatory cells
How do changes in blood flow in acute inflammation occur?
Vasodilation - controlled by histamine. Increases vascular permeability
What occurs during exudation of fluid in acute inflammation?
Exudation of protein rich fluid into tissues
Blood flow slows (stasis) leading to tumour
Fluid in tissues causes oedema
What is the difference between exudate and transudate
Exudate - protein rich fluid lost during inflammation
Transudate - protein poor fluid lost as a result of hydrostatic pressure
What are the chemical mediators for vascular leakage in acute inflammation?
Histamine, IL-1, TNF
How do neutrophils enter the tissues in acute inflammation?
margination - stasis causes neutrophils to line up at edge of vessels
Rolling - neutrophils roll along endothelium, adhering intermittently
Adhesion - stick more avidly
Emigration - neutrophils move through gaps between endothelial cells
What is chemotaxis?
The movement of a substance towards a high concentration of a chemoattractant
What are the chemoattractants for neutrophils in acute inflammation?
C5a, LTb4 or bacterial peptides
What are the ‘killing mechanisms’ of neutrophils in acute inflammation?
O2 dependent - superoxide/h2o2
O2 independent - hydrolase enzymes/bacteridal permeability increase protein
What is shock?
A clinical symptom of circulatory failure - low BP leading to poor cardiac output and therefore tachycardia
How is acute inflammation resolved?
Vascular changes stop
Exudate drains into lymphatics
Neutrophils are phagocytosed by macrophages
Mediators have short half lives, and therefore break down
Dilution of mediators by exudate
treatment: incision and drainage
How can chronic inflammation arise?
take over from acute inflammation
arise de novo
develop alongside acute inflammation in persistent irritation
How are macrophages stimulated to enter tissues?
Gamma interferon from T/NK cells
What signalling molecules do macrophages release?
IL-8 - chemoattractant for neutrophils
NO - vasodilation
TNF/IL-1 - fever
What are the functions of lymphocytes in chronic inflammation?
B lymphocytes > plasma cells > immunoglobulins
T lymphocytes - release mediators
What are giant cells? Include types
multinucleate cells made by fusion of many macrophages
Langhans - horseshoe nuclei, TB
Foreign body - less organised
Touton - fat necrosis
What is granulamatus infection?
Infection with presence of granuloma - an aggregation of epitheloid macrophages surrounded by lymphocytes. Functions to wall off substances which are harmful but cannot be removed
Giant cells may be present - but not always!
What is ulceration?
Necrosis through mucosa - commonly found in the stomach linked to helicobacter pylori
