Term
| Name the three normal functions of a cell |
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Definition
- continuous supply of nutrients
- constant removal of waste products
- normal cell environment |
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Term
| name the four steps leading from stress or injury to necrosis |
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Definition
1. stress/injury
2. adaptive response
3. cell degeneration
4. necrosis |
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Term
| The consequences of cellular injury depend on what four characteristics of that cell? |
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Definition
type
status
adaptability
genetic make up |
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Term
| which four intracellular systems of the cell are most vulnerable? |
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Definition
cell membrane integrity
ATP generation
metabolism (protein synthesis)
integrity of genetic apparatus |
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Term
| Are secondary effects of cell injury confined to the area of initial locus of injury? |
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Definition
| no. multiple secondary effects occur throughout the cell regardless of the initial locus of injury. |
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Term
| does morphological change happen before or after function loss? |
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Definition
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Term
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Definition
| abnormality of cell biochemical function, a recgonizable strucutal change, or combination of thw two. |
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Term
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Definition
| static condition in which the cell function at a sub-maximal level, but still sufficient to maintain life. |
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Term
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Definition
| irreversible state, either as progression from degeneration or great injury |
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Term
| (brief) what are they four causes of impaired energy production? |
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Definition
hypoxia
hypoglycaemia
enzyme inhibition in the respiratory chain
uncoupling of oxidative phosphorylation |
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Term
| describe hypoxia, and its four causes. |
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Definition
hypoxia is an in-sufficent oxygen supply to cells.
it results from:
- any disease or obstruction of the respiratory system
- decreased ability of blood to cary oxygen (due to fewer RBCs or in-sufficent/altered hemoglobin)
- failure of the oxygenated blood to flow adequately to the tissue (due to vessel obstruction or heart failure)
- insufficient oxygen in inspired air (ie high altitude) |
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Term
what is hypoglycaemia ?
why does it impair energy production? |
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Definition
hypoglycaemia is an abnormally diminished content of glucose in blood.
it impairs energy production because glucose is the main substrate for energy production. |
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Term
| how would cyanide lead to impaired energy production? |
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Definition
It would lead to enzyme inhibition of the respiratory chain.
specifically: it would negatively effect cytochrome oxidase, whose role it is in the electron transport chain to help establish a transmembrane difference of proton electrochemical potential which is used by ATP synthase to produce ATP. |
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Term
what are the three major effects of impaired energy production? (brief)
these three effects first affects cells with high levels of what? |
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Definition
intracellular accumulation of water and electrolytes
swelling of organelles
switch to anaerobic metabolism
first affects cells with highest basal metabolic rate (ie highest oxygen demand) such as brain cells) |
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Term
| describe the 4 steps that occur in intracellular accumulation of water and electrolytes |
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Definition
1. a lack of ATP leads to dysfunction of Na/K pump
2. water moves in and leads to swelling/hydrophobic change (granular, vacuolated cytoplasm).
3. cell becomes swollen
4. electrolytes lead to inhibition of enzymes and changes in electrical activity of the cell |
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Term
| describe what occurs during the swelling of cellular organelles. |
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Definition
| the swelling of the mitochondria leads to the physical uncoupling of phosphorylation. this leads to a granular/vacuolated appearance that allows it to be visible under a light microscope. |
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Term
| What are the four mechanisms of cellular injury? (brief) |
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Definition
impaired energy production
impaired cell membrane function
metabolic derangements
genetic abnormalities |
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Term
| what occurs to the cell during a switch to anaerobic metabolism? |
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Definition
| lactic acid production leads to an increased intracellular pH. further disruption of the organelles membrane occurs and there is a release of lysosomal enzymes. autolysis occurs. |
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Term
| briefly list the three causes of impaired cell membrane function |
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Definition
free radicals
activation of the complement system
lysis of the membrane |
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Term
| describe what free radicals are and how they impair cell membrane function. name the three reactions invovled in this impairment. |
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Definition
free radicals are highly reactive particles with an unpaired electron in the outer shell. they are extremely unstable and readily react with (in)organic chemicals.
They impair cell function by attacking nucleic acids and membrane moelcules. this initiates an autocatalytic reaction.
reactions:
- lipid peroxidation of membranes (target: double bonds which proudces peroxides)
- DNA fragementation (target: thymine which produces ss breaks)
-cross linking protentins which enhances degrdation and loss of function |
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Term
| lysis of the membrane, which leads to impaired cell membrane function, is induced by what three things? |
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Definition
enzymes with lipase-like activity (i.e. pancreatic liapse digests fat)
virsues (either by direct insretion or through immune response)
physical and chemical agents (such as temp extremes |
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Term
| what are the three effects of impaired cell membrane function (brief) |
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Definition
loss of structural integrity
loss of function
deposition of lipofuscin pigment |
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Term
| the loss of function of selectively permeability created by an impared cell membrane function can lead to what? |
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Definition
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Term
Lipofuscin pigment is an effect of impaired cell membrane function.
It is particularly found where?
It's contains remnants of?
It has what effect on cell function?
Is it a normal or abnormal process?
It is caused by what? |
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Definition
Is particularly found in myocardial, liver and neuron cells
It consists of remanence of cell membrane i.e. lipids and proteins
It has no effect on cell function.
It is a normal process of aging.
Is caused by a lack of cellular antioxidants, which normally prevents lipid peroxidation injury |
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Term
Metabolic derangements are primarily caused by what?
List the three main intracellular accumulations. |
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Definition
Intracellular accumulation of various substances.
Three main intracellular accumulations:
Fatty degeneration
iron deposition
bilirubin accumulation |
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Term
Describe fatty degeneration.
What is it caused by?
How does the fatty liver appear? |
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Definition
Triglyceride accumulation in the cytoplasm of parenchymal cells. It is a nonspecific response to many types of injury.
It is caused by anything which disrupts the balance of fat processing and exporting.
In cat it is caused by anything which causes the cat to eat considerably less than normal.
The fatty liver appears enlarged, pale, tan-yellow colour and Greasy. |
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Term
| Iron deposition, in metabolic derangement, has local accumulation when? |
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Definition
| When hemoglobin is broken down at sites of hemorrhage |
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Term
| Iron is deposited in local macrophages or connective tissue as? |
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Definition
| Hemosiderrin (Hemoglobin derived pigment) |
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Term
| Describe the process of iron deposition after trauma. How does it harm cells? how does it appear? |
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Definition
Extravasation occurs, where Blood escapes the vessels, moving to the interstitium (tissue spaces).
Hemosiderrin (hemoglobin derived pigment)
Deposition particularly in bone narrow, spleen and liver.
However, it does not harm the cell.
It appears as golden brown granules within the cytoplasm. |
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Term
| Describe hemochromatosis. |
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Definition
| A rare genetic defect in iron metabolism, leading to intracellular accumulation of ferric iron. This leads to toxic free radicals and therefore, tissue damage. |
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Term
| Describe Bilirubin accumulation, ending with its excretion. |
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Definition
Old red blood cells undergo hemoglobin breakdown. This leads to the porphryin ring catabolizing to Bilirubin. It then binds to albumin, and is carried in plasma in LS form to liver. It is then conjugated To glucuronide and becomes WS.
It then travels to either the bile duct and then the intensities, Or, to the kidney where it is then excreted urine as urobilinogen. |
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Term
Jaundice has what relation to bilirubin?
what does this level of bilirubin show in terms of disease. |
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Definition
It is cause by an increase in serum bilirubin.
these spikes in bilirubin, ie jaundice, is only a SIGN of disease. not the actual disease. |
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Term
| name three sources of serum bilirubin |
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Definition
| senescent RBCs (old/dying), hepatic hemoproteins premature destruction of newly formed RBCs |
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Term
| briefly list the eight disease related to bilirubin accumulation. |
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Definition
hemolytic jaundice
hepatocellular jaundice
obstructive jaundice
neontal jaundice
Crigler-Najar Syndrome I
Crigler-Najar Syndrome II
Gilbert Syndrome
Dubin-Johnson Syndrome |
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Term
| name and describe the four types of jaundice |
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Definition
HEMOLYTIC JAUNDICE
- excessive breakdown of RBCs and consequent production of bilirubin. Unconjugated bilirubin accumulates as LS, so it can't be excreted.
HEPATOCELLULAR JAUNDICE
- injured liver; reduced uptake, impaired conjugation or decreased excretion mechanisms. Both WS and LS bilirubin levels increase
OBSTRUCTIVE JAUNDICE
- impaired bile flow through the bile duct. Either intrahepatic or extra-hepatic. increased conjugated WS bilirubin levels
NEONATAL JAUNDICE
- hepatic conjugation and excretion machinery matures only at two weeks of age |
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Term
| Give descriptions of the the four diseases related to bilirubin accumulation that aren't a form of jaundice. |
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Definition
CRINGLER-NAJAR SYNDROME I
- rare autosomal recessive. fatal. lack of enzymes for conjugation
CRINGLER-NAJAR SYNDROME II
- less severe, partial defect
GILVERT SYNDROME
- mild, fluctuating unconjuagted hyperbilirubinemia due to decreased levels of glucuronosyltransferase becuase of gene mutation
DUBIN-JOHNSON SYNDROME
- defect in transport portein responsible for excretion. conjugated hyperbilirubinemia. pigmented liver. no functional problems. |
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Term
| contrast between bilirubin deposition in connective tissue and parenchymal cells. |
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Definition
CONNECTIVE TISSUE
- (skin, sclera): yellowish discolouration, but no functional abonromality
PARENCHYMAL CELLS
- (functional parts of an organ): cellular injury |
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Term
| describe the forms and restults of bilirubin deposition in parenchymal cells of obstructive jaundice and neonatal hemolysis. |
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Definition
OBSTRUCTIVE JAUNDICE
- deposition in liver cells-> toxic cellular injury-> necrosis
NEONTAL HEMOLYSIS
- acummulation in brain cells -> neuronal dysfunction -> kernicterus (bilirubin-induced brain dysfunction) |
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Term
| name the causes of genetic abnormalities |
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Definition
inherited or acquired through:
-somatic mutations due to radiation
- mutagenic chemicals and virsues |
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Term
| briefly list the four effects of genetic abnormalities and their resulting afflictions. |
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Definition
INTERFERENCE WITH MITOSIS
- most damage done in the actively diving cells (bone marrow, epithelium).
- damage to RBCs -> anemia (decrease in number of red blood cells)
- damage to inestinal mucosa -> intestinal dysfunction, diarrhea, hemorrhange
FAILURE OF SYNTHESIS OF STRUCTURAL PROTEINS
- if vital parts affected, necrosis
FAILURE OF GROWTH REGULATING PROTEINS
- cancer
FAILURE OF ENZYME SYNTHESIS
- if in embryo: congenital disease (condition existing at birth)
- if adult: necrosis |
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Term
| list and describe the three forms of cell degeneration recognition |
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Definition
GROSS
- affected tissue may appear pale, swollen, or enlarged, and more turgid (Turgor pressure pushes the plasma membrane against the cell wall)
MICROSCOPIC
- cellular swelling (clear vacuoles), fatty change (lipid vacuoles)
ULTRASTRUCTURAL CHANGES
- PM alterations (blebbing [irregular bulge in the plasma membrane of a cell], blunting, distortion of microvili, looesning of intracellular attachments)
- mitochondrial changes: swelling and appearnace of phospohlipid- rich amorphous densities (blob)
- dilation of ER: with detachment of ribosomes and dissocation of polysomes ( cluster of ribosomes, bound to a mRNA molecule)
- nuclear alternations: disaggreation (pushing away) of granular and fibrillar elements |
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Term
| how much time needs to pass before the changes of necrosis are visible by light microscopy |
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Definition
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Term
| appearance of necrosis is the result of |
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Definition
| concurrent enzymatic digestion fo the cell and denaturation of proteins |
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Term
| briefly list the three categories of morphologic evidence of necrosis |
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Definition
cytoplasmic
nuclear(microscopic)
gross evidence |
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Term
| describe what is observed (4 things) during cytoplasmic evidence for necrosis. |
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Definition
- more homogenous and deeply staining blue (due to denaturation and loss of ribosomes)
- vaculoated (bubbly) appearance (due to failure of PM Na/K pump)
- autolysis: cell self digestion leads to fuzzy appearance (due to release of lysosomal enzymes)
- calcification of the dead cells (due to abnormal depostion of calcium salts). can be seen in assocation with necrosis of any type |
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Term
| describe what is observed (3 things) during nuclear evidence for necrosis. |
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Definition
- more definitive indectaor of necrosis than cytoplasmic eividence
- clumping of nuclear chromatin -> nucleus becomes smaller and more densely staining (pyknosis)
- pyknotic nucleus can break down into fragments (karrhyorhexis) or undergo complete lysis (karrhyolisys) due to action of lysosomal enzymes |
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Term
| briefly list the 5 factors of gross evidence for necrosis. |
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Definition
coagulation necrosis
liquefaction necrosis
caseous necrosis (cheesy appearance)
enzymatic fat necrosis
non-enzymatic fat necrosis |
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Term
| describe coagulation necrosis, a factors of gross evidence for necrosis. |
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Definition
- characteristic of hypoxic (reduced oxygen) death of cells in all tissues, expect the brain
- denatured protein; basic cell outline presevered, but nucli are lost. pale, dry demarcated areas
- occurs at injection sites or during infarcts (tissue death (necrosis) caused by an obstruction of the tissue's blood supply) |
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Term
| discribe liquefaction necrosis of gross evidence for necrosis. |
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Definition
- characteristic of focal bacterial or fungal infection in CNS
- dominant enzymatic digestion |
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Term
| describe caseous necrosis of gross evidence for necrosis |
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Definition
due to TB infection
chessy, white, sturcturless, amorphous, granular debris
- granulomatous inflammation (tiny collection of immune cells) |
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Term
| describe enzymatic fat necrosis (as gross evidence for necrosis) |
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Definition
-pancreatic enzyme release into adjacent tissue (due to pancreatic injury or acute pancreatitis)
- chalky white; TGAs-> FFAs + glycerol, FFAs + Ca -> soaps |
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Term
| describe non-enzymatic fat necrosis (a type of gross evidence for necrosis) |
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Definition
occurs in other fat deposists (breasts, subcutaneous tissue), usaully following tramuma
- granulomatous (collection of immune cells) inflammatory response |
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Term
| briefly list the 6 clinical pieces of evidence that necrosis may have occurred. |
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Definition
altered function
gangrene
secondary bacterial infection
systemic effects
local effects
release of enzymes from necrotic cells |
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Term
| describe what causes altered function (a peiece of clinical evidence that necrosis has occured.) |
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Definition
| results if suffient number of cells become necrotic. the limit dpeneds on the type of tissue affected. ie large reserve in liver, smaller in brain. |
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Term
| describe gangrene (a peice of evidence that necrosis has occured). differentiate between wet and dry. |
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Definition
gangrene is a state of regional tissue necrosis caused by ischemia (a restriction in blood supply to tissues, causing a shortage of oxygen and glucose needed for cellular metabolism (to keep tissue alive)) .
- variably complicated by invasion of the affected tissue by saprophytic microorganimss (processing of dead or decayed organic matter)
-dry gangrene : caused by arterial obstruction, most commonly affecting the extremities (become dark, dry and shrivelled). clearly demaracted (put boundrary around) from healthy tissue
- wet gangreen: severe bacterial infection is superimposed on ischemic necrosis
- the area is swollen, reddish balck and foul smelling. liquefaction of dead tissue. not clearly separated from adjacent viable tissue. |
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Term
| describe secdonary bacetrial infection as clincial evidence that necrosis has occured |
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Definition
| bacteria can grow easily on necrtoic tissue, but if no blood supply then no inflammatory response. |
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Term
| name and give reasons for two systemic effects that are evidence that necrosis has occured. |
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Definition
fever (due to relase of pyrogens, fever inducing agents, from nectoric cells)
increased WBCs due to inflammaotry response |
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Term
| why is relase of enzymes from nectoric cells (a peice of evidence that necrosis has occured), useful for diagnosis? |
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Definition
| becuase certain enzymes can be assayed in serum and can lead to orginial site of injury. |
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Term
| list and describe 5 changes that occur post motem. |
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Definition
RIGOR MORTIS
POST MORTEM LIVIDITY
- graviational settling of the blood in dependent (lower) parts. subsequent breakdown of hemoglibin proudces typical green discoloration of the skin
POST MORTEM BLOOD CLOTTING
- formation of large clots in places such as chambers of the heart
PUTREFACTION
- fermentaion caused by saprophytic bacteria. Gas accumulation may produce rupture of the stomach or a typical foamy liver
AUTOLYSIS
- disintegration of tissues which occurs after death due to the action of their own enzymes |
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