Pathology 1 Flashcards
What is the difference between aetiology and epidemiology?
Epidemiology = How common? What sort of people get it? How does it spread? Aetiology = Basic causes eg. microorganisms, molecular defects
What is meant by the prefix ANA?
Absence
What is meant by the prefix DYS?
Disordered
What is meant by the prefix HYPER?
Excess over normal
What is meant by the prefix HYPO?
Deficiency below normal
What is meant by the prefix META?
Change from one state to another
What is meant by the suffix -ITIS?
Inflammatory process
What is meant by the suffix -OMA?
Tumour
What is meant by the suffix -OSIS?
State or condition
What is meant by the suffix -OID?
Bearing a resemblance to
What is meant by the suffix -PENIA?
Lack of
What is meant by the suffix -CYTOSIS?
Increase number of cells
What is meant by the suffix -ECTASIS?
Dilation
What is meant by the suffix -PLASIA?
Disorder of growth
What is meant by the suffix -OPATHY?
Abnormal state lacking specific characteristics
What did Virchow say about cell injury and disease?
Injury to the smallest unit in the body, the cell, is the basis of all disease
What are the 4 things needed to maintain a steady state in a cell?
1) Preservation of genetic integrity
2) Normal enzyme content
3) Intact membranes and transmembrane proteins
4) Adequate supply of substrates and oxygen
What is the definition of cell injury?
Biochemical and/or morphological changes which occur when the steady state of a cell is perturbed by adverse influences
What is one of the ways that a cell copes with stress and how can this lead to cell injury?
Cell adaptation
If cell has an inability to adapt to this stress then cell becomes injured
Once a cell becomes injured one of 2 things can happen, what are they?
1) If the injury is mild then the cell can recover and the injury is reversible
2) If the injury is severe/progressive then the cell becomes irreversibly injured and dies - either by apoptosis or necrosis
What is the difference between hyperplasia and hypertrophy?
Hypertrophy - No increase in number but cells themselves actually get bigger leading to tissue getting bigger
Hyperplasia - an increase in the number of cells
What are the 3 ways in which a cell can adapt to stress?
1) Increased cellular activity - hypertrophy/hyperplasia
2) Decreased cellular activity - atrophy
3) Change in cell morphology
Give an example of how a cell of the adrenal gland adapts to the stress of changes in the pituitary axis with the use of exogenous steroids?
Decrease in cell activity - adrenal gland atrophies
Give an example of how myocytes adapt to cope with increased systemic resistance?
Hypertophy of the myocytes - bigger heart muscle to pump harder and overcome resistance
What are the 5 main types of cell injury?
1) Lack of oxygen availability - ischaemia
2) Physical trauma - includes thermal and mechanical
3) Chemical agents - acid/alkali balance altered/drugs
4) Infectious organisms
5) Irradiation
Other than the 5 main types of cell injury what are the 4 other common types?
1) Immunological
2) Lack of essential vitamins/nutrients
3) Genetic disorders
4) Ageing - being old leads to inefficiency in some cell processes
What is the difference between hypoxia and anoxia?
Hypoxia - insufficient oxygen
Anoxia - absence of oxygen
What is ischaemia?
Lack of blood flow (ie. ischaemia often causes hypoxia/anoxia)
What is infarction?
Cell death due to lack of oxygen
Other than ischaemia, for what 2 other reasons may hypoxia occur?
1) Not enough oxygen in blood to start off whit
2) Cells might not be able to use available oxygen eg. cyanide poisoning
Why can reoxygenation of hypoxic/anoxic tissue lead to further cell injury in some cases?
In reperfusion of tissues you can get generation of oxygen free radicals
In terms of physical trauma causing cell injury, in what 2 main ways can mechanical trauma lead to cell injury?
1) Disruption of cell structure
2) Thrombosis leading to ischaemia
Why can mechanical trauma to a tissue cause cell death. by ischaemia?
Damage to cells in walls of blood vessels in that tissue due to mechnical trauma can lead to the formation of a thrombus which can cause ischaemia and infarction
In physical trauma in what 2 ways can the extremes of temperature cause cell injury?
1) Heat denaturation of proteins
2) Ice crystals
How can fever cause cell injury by physical trauma (ie. extremes of temperature)?
It is possible to become pyrexial enough to alter your metabolism and denature proteins
Name 6 kind of chemical agents (chemical agents cause cell death by many different modes of action including damage to macromolecules and metabolism) which can cause cell death?
1) Alcohol
2) Tobacco smoke
3) Drugs
4) Poisons
5) Environmental agents
6) Occupational agents (Asbestos)
By what general mechanism do bacteria cause cell death?
The production of toxins
What are the 2 kinds of toxins produced by bacteria and how do they differ?
1) Endotoxins - released when bacteria die
2) Exotoxins - released by living bacteria
How do viruses cause cell injury?
Hijacking of cell machinery and causing lysis
Other than release of toxins by bacteria and invasion of cells by viruses, in what other way can infectious agents lead to cell injury?
Collateral damage to surrounding tissue due to inflammatory process
How does irradiation cause cell injury?
Ionising - generation of free radicals which cause cell injury and direct damage to macromolecules
What kind of tissues are very sensitive to damage by irradiation, give 3 examples?
Tissues with high physiological turnover of cells
1) Bone marrow
2) Gonads
3) Intestines
Give 3 examples of tissues that have very low sensitivity to irradiation?
1) Uterus
2) Pancreas
3) Adrenal
Can irradiation induce an inflammatory response? If so, when?
It can, several hours after exposure
What are the 5 targets of cell injury (ie. the things that tend to be damaged)?
1) Mitochondrial function
2) Membrane integrity and function
3) Protein synthesis
4) Cytoskeleton
5) Genetic apparatus
When the mitochondria are damaged this leads to reduced ATP, how does this lead to cellular ‘cloudy’ swelling?
Less ATP
Activity of ATP driven Na pump is reduced, influx of Na and Ca leading to osmotic gaining of water and cells swells
Why do you get lipid deposition in cells with damaged mitochondria?
Less ATP
Increased glycolytic pathway which depletes glycogen stores and leads to a build up of lactic acid, lowering cell pH
The low levels of pH and ATP in the cell cause ribosomes to detach from the RER and a reduction in protein synthesis - lipids are transported out of the cell carried by lipoproteins (which aren’t made) so lipid gets deposited in the cell, leading to fatty swelling
Why do you get clumping of nuclear chromatin in cells with damaged mitochondria?
Less ATP
Increased glycolytic pathway - build up of lactic acid
Lower pH causes clumping of chromatin
What are the 7 things that happen in a cell, with damaged mitochondria?
1) Cellular swelling
2) Loss of microvilli
3) Blebs
4) ER swelling
5) Lipid deposition
Alcohol causes damage to the liver cells, what 2 things occur?
1) Cell (cloudy) swelling
2) Fatty change, fat deposition
What are free radicals?
Highly reactive ions or molecules with single, unpaired electron in their outer orbit
In what 2 ways can free radicals cause damage to cells?
1) Chain reaction with molecules in membranes to produce additional free radicals
2) Damages proteins and nucleic acids (can cause cells to die by apoptosis)
What 2 things detoxify free radicals normally?
1) Superoxide dismutase
2) Anti oxidants eg. Vitamin A, C and E
When are free radicals used physiologically?
In bacterial killing by neutrophils and macrophages which depends on the formation of superoxide
Name 4 things which can cause damage to cell membranes?
1) Bacterial toxins
2) Viral proteins
3) Complement (MAC complex)
4) Cytolytic lymphocytes
When membranes are ruptured this leads a breakdown in metabollite gradients, the influx of what ion causes deleterious cellular affects and why?
Influx of Ca2+
activates a number of enzymes:
1) ATPase - hastening ATP depletion
2) Phospholipases - Cause membrane damage
3) Proteases - break down membrane and cytoskeletal proteins
4) Endonucleases - responsible for DNA fragmentation
What is necrosis?
Cell death as a result of lethal cell injury
Is necrosis an active or passive process and does it incite an inflammatory reaction?
Passive process
Incites an inflammatory reaction
What are the 5 distinct morphological types of necrosis?
1) Coagulative - most common
2) Caseous - necrosis that occurs in TB
3) Colliquative
4) Gangrene - wet and dry
5) Fat, fibrinoid
Coagulative necrosis is typical of what kind of injury?
Ischaemic injury - except to brain
How is coagulative necrosis characterised? 4
- Denaturation of intracytoplasmic protein
- Dead tissue becomes swollen and firm
- Tissue shows retention of microscopic architecture
- Cellular proteins may leak out into blood
How is colliquative necrosis characterised and where does it prinicipally occur?
Necrotic tissue is liable to total liquefaction and site is eventually marked by a cyst
Typically occurs in brain injury due to haemorrhage
Caseous necrosis is typical of what disease?
TB
How is caseous necrosis characterised?
Cheese like
Cellular detail destroyed in this area, which is surrounded by granulomatous inflammation
Dead tissue lacks any structure
Gangrene is a type of what kind of necrosis?
Coagulative necrosis
Name the 2 types of gangrene, give examples of each?
1) Wet - infarct bowel is prone to develop wet gangrene
2) Dry - dry gangrene of the foot in diabetes
What is apoptosis, is it active or passive?
Programmed cell death
Active, requires energy
Name 3 physiological and 3 pathological reasons why apoptosis may occur?
Physiological 1) Embryogenesis 2) Involution (of an organ) 3) Elimination of self reacting lymphocytes Pathological 1) DNA/Protein damage 2) Viral infections 3) Cell killing by cytotoxic T cells
What are the 2 broad pathways of apoptosis and how do they differ?
1) Intrinsic - Cell signals itself to undergo apoptosis without outside influence
2) Extrinsic - Something binds to receptors and feeds through the cell and stimulates apoptosis
What are caspases?
These are the effector molecules of apoptosis
Enzyme cascade, last step in stimulating apoptosis
Which 2 molecules normally kept in the mitochondria activate caspases?
1) Apoptosis initiating factor (AIF)
2) Cytochrome C
What is the P53 molecule, what is its role in cancer?
P53 is activated by DNA damage and causes the elimination of damaged cells by apoptosis (by causing release of AIF and Cytochrome C from mitochondria)
Mutations to P53 are very common in tumours, thus allowing cells to accumulate genetic abnormalities and become malignant
What is the difference in number of cells killed by apoptosis compared to necrosis?
Apoptosis - single cell
Necrosis - Multiple cells
What is the difference in cell size in cells that undergo apoptosis compared to necrosis?
Apoptosis - Reduced size
Necrosis - Enlarged
What is the difference to the plasma membrane in cells that undergo apoptosis compared to necrosis?
Apoptosis - intact
Necrosis - Disrupted
What happens to the nucleus in a cell that undergoes apoptosis compared to necrosis?
Apoptosis - Fragmentation -> apoptotic bodies
Necrosis - Pyknosis -> karyorrhexis -> karyolysis
Does apoptosis cause adjacent inflammation?
No
What is the difference in what happens to the cell contents of cells that undergo necrosis compared to apoptosis?
Necrosis - Enzymatic digestion - may leak out of cell
Apoptosis - Intact, may be released into apoptotic bodies
Name 8 important functions of the liver?
1) Glucose metabolism
2) Barrier to sepsis
3) Lipid metabolism
4) Amino acid metabolism
5) Vitamin storage A, B12, D and iron
6) Chemical detoxification and metabolism (alcohol and some drugs)
7) Bilirubin metabolism
8) Production of clotting factors
Why is ischaemic injury to the liver very uncommon?
It has 2 blood supplies - hepatic artery and portal vein, its unlikely that blood flow from both of these will be stopped
What are idiosyncratic hepatotoxins?
Drugs that cause injury to a very small number of people who take them
What are intrinsic hepatotoxins?
Drugs that in high doses cause injury to everyone
Why does paracetamol toxicity occur?
Paracetemol metabolised by enzyme 1 (Glucuronyl transferase), if thats overwhelmed its metabolised by enzyme 2 (Sulphotransferase) if thats overwhelmed its metabolised by enzyme 3 to make a toxic product NAPQ1 which is mopped up by glutathione but if glutathione is overwhelmed then NAPQ1 binds covalently to cell membrane proteins resulting in necrosis of liver cells
What is the first treatment for paracetemol overdose, what does this do?
Acetylcysteine - regenerate the glutathione to mop up more NAPQ1
Hepatocytes in which part of the liver are most vulnerable to toxins and why?
Hepatocytes around the hepatic veins
This is where most of the detoxification takes place
These also have blood with the lowest oxygen concentration so are most vulnerable to injury
What kind of cell death does viral hepatitis cause?
Apoptosis
What kind of cell death occurs in hepatocytes in paracetemol poisoning?
Necrosis
What are the clinical signs and symptoms seen in liver cell necrosis (in order)? 5
1) Raised AST and ALT in blood
2) Jaundice
3) Hepatic encephalopathy (coma)
4) Bleeding tendency
5) Renal failure (hepatorenal failure)
Why would raised AST and ALT be seen in the blood in liver necrosis?
Released from the hepatocytes as they die
Why is jaundice seen in liver cell necrosis?
Failure of bilirubin metabolism, mostly conjugated hyperbilirubinaemia
Why is hepatic encephalopathy seen in liver cell necrosis?
failure of liver to detoxify nitrogenous compounds
Circulation of excitatory amino acids
Why is a bleeding tendency seen in liver cell necrosis?
Failure to synthesise proteins and thus clotting factors
Why is hepatorenal failure seen in liver cell necrosis?
Shock causes low glomerular filtration
What is shock?
a syndrome featuring low blood pressure, a prejudice blood supply to important organs such as the brain and heart and low kidney output
What 3 kind of patients have been found to be at higher risk of liver damage after paracetemol overdose?
1) Malnourished, or fasting patients
2) Patients who take enzyme inducing drugs
3) Patients who regularly drink alcohol to an excess
After paracetemol poisoning patients can start to become irritable, what is this a sign of and what can it lead to?
In acute liver failure cerebral oedema can develop quickly, irritability is the initial sign of this and it can quickly lead to patients becoming unconcious
Why is it necessary to protect the head of a patient with hyper acute liver failure such as that in paracetemol overdose?
Clotting is abnormal - risk of bleeding on the brain
What 3 things tell you the most about a patients prognosis after paracetemol poisoning (ie. in acute liver failure)?
NOT ALT/AST
1) Clotting - prothrombin time
2) Kidney function
3) Signs of encephalopathy
Why can the failure of one organ lead to multi organ failure?
One organ failing to perform its function puts extra strain on other organs which in turn can lead to them failing and thus multiple organ failure
What is meant by encephalopathy?
Any degenerative or non-inflammatory disorder affecting the brain in a widespread manner (ie. effecting brain function)
