Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Mechanisms of Disease > 1) Cell Injury > Flashcards

1) Cell Injury Flashcards

1
Q

Suggest some possible causes of cell injury and/or death.

A
  • Hypoxia
  • Toxins
  • Heat/cold
  • Trauma
  • Radiation
  • Micro-organisms
  • Immune mechanisms
  • Dietary insufficiency, deficiency and excess
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define necrosis.

A

Changes that occur after cell death in living tissue, largely due to progressive degradative action of enzymes on lethally injured cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define apoptosis.

A

Programmed cell death aka cell death induced by regulated intracellular program – cells activate enzymes that degrade cells’ own nuclear DNA and proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the four main causes of hypoxia?

A
  • Hypoxaemic hypoxia
  • Anaemic hypoxia
  • Ischaemic hypoxia
  • Histiocytic hypoxia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is hypoxia?

A

Where the body body or some tissue within the body is deprived of oxygen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the difference between ischaemia and hypoxia?

A

Ischaemia is the loss of blood supply to a tissue, which results in a lack of oxygen, glucose and other essential tissue requirements. Hypoxia on the other hand is where there is a lack of oxygen to a tissue, possibly due to ischaemia but it doesn’t have to be. Therefore, ischaemia can result in a much more serious injury.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Suggest some toxins that COULD lead to hypoxia. (just list bad things you shouldn’t be ingesting/drinking/eating)

A
  • Glucose and salt in hypertonic solutions
  • High concentration of oxygen (free radicals)
  • Poisons
  • Pollutants
  • Insecticides/herbicides
  • Asbestos
  • Alcohol/drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the two main ways the immune system can damage cells accidentally?

A
  • Hypersensitivity reactions - host tissue is injured secondary to an overly vigorous immune reaction e.g. urticaria (aka hives)
  • Autoimmune reactions - immune system fails to distinguish self from non-self, e.g. Grave’s disease.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Suggest the four structures of the cell that are common sites of injury.

A
  • Cell membranes (plasma membrane and organellar membranes)
  • Nucleus (DNA)
  • Proteins
  • Mitochondria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the reversible cell changes in ischaemic hypoxia.

A

As you can’t get oxygen to the tissue, you can’t complete as much oxidative phosphorylation, so you get cell changes:

  • Less ATP means reduced activity of the Na+ /K+ pump which leads to the cell/organelle swelling up as water follows Na+ and Na+ isn’t leaving
  • Anaerolic metabolism kicks off increasing lactic acid reducing pH in the cell which leads to chromatin clumping
  • Reduced ATP leads to less protein synthesis and detachment of ribosomes leading intracellular accumulations e.g. fat/denaturated protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the irreversible cell changes in ischaemic hypoxia.

A

At some point, which is still not clearly understood, damage becomes irreversible and it has something to do with massive cytosolic accumulation of Ca2+, especially from stores in organelles such as ER and mitochondria. This calcium activates shitloads of enzymes such as:

  • ATPases (reduced ATP)
  • Phospholipases (decreased phospholipids)
  • Proteases (disruption of membrane/cytoskeletal proteins)
  • Endonucleases (nuclear chromatin damage)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are free radicals?

A

Reactive oxygen species - single unpaired electron in an outer orbit, an unstable configuration hence reactions with other molecules, often producing further free radicals.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

When can free radicals be produced?

A
  • Chemical and radiation injury
  • Ischaemia-reperfusion injury
  • Cellular ageing
  • High oxygen concentrations
  • Produced by leukocytes (WBCs) in oxygen dependent killing (oxidative burst)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Suggest two types of reaction that can produce hydroxyl ions? (OH•)

A
  • Fenton reaction

- Haber-Weiss reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How can radiation produce hydroxyl ions?

A

Directly lyse water (H2O) to produce OH•

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How can O2- and H2O2 be generated in normal metabolic reactions?

A
  • Oxidative phosphorylation can yield O2- and H2O2.

- Cytosolic reactions and p450 enzymes in the endoplasmic reticulum also generate O2- and H2O2.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe how free radicals can damage cells.

A
  • The key target of free radicals is unsaturated lipids in the cell membrane which is called lipid peroxidation, kicking off an autocatalytic chain yielding more radicals.
  • Can also damage proteins by protein fragmentation and cross linkage.
  • Can also damage DNA by single strand breakages (genomic and mitochondrial)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How can the radical autocatalytic chain be terminated?

A
  • Spontaneous decay
  • Enzymes (superoxide dismutase (SOD) and catalases/peroxidases)
  • Free radical scavengers like vitamin E/pre Vitamin A (in membranes) and vitamin C (cytosol)
  • Storage proteins sequester transition metals (iron) which are Fenton reaction substrates
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are heat shock proteins?

A

A group of proteins that are responsible for the upkeep of other cellular proteins. They are really important when protein synthesis/folding goes astray, they either help it back on track (synthesis of chaperones) or if not possible the mis-folded proteins are destroyed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe some changes that can be seen under a light microscope after cell injury.

A

-Cytoplasmic changes:
+reduced pink staining due to accumulation of water (reversible)
+later increased pink staining due to detachment and loss of ribosomes and accumulation of denatured proteins (irreversible)

-Nuclear changes:
+clumped chromatin – very subtle (reversible)
+followed by various combinations of pyknosis, karryohexis and karryolysis (dissolution) (irreversible)

-Abnormal accumulations (damaged proteins and abnormal metabolites)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe some reversible changes that can be seen under an electron microscope after cell injury.

A

-Swelling of the cytoplasm/organelles due
to Na/K+ pump failure
-Clumped chromatin due to reduced pH
-Autophagy due to catabolic response from
low available energy
-Ribosome dispersion due to failure of
energy-dependant process of maintaining
ribosomes
-Cytoplasmic blebs - symptomatic of cell
swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

In a H&E stain what colour does the nucleus and cytoplasm stain?

A
  • Nucleus stains blue

- Cytoplasm stains pink

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Suggest some abnormal accumulations in alcoholic liver disease.

A
  • Mallory’s hyalin (damaged protein) which is seen due to accumulation of altered keratin filaments.
  • Accumulation of fat, a type of abnormal metabolites.
24
Q

Describe some irreversible changes that can be seen under an electron microscope after cell injury.

A

-Nuclear changes - pyknosis, karyolysis and karyorrhexis
-Lysosome rupture – due to membrane
damage
-Myelin figures due to membrane defects
-Lysis of enodoplasmic reticulum due to
membrane defects

25
Q

What are the four types of necrosis?

A
  • Coagulative
  • Liquefactive
  • Caseous
  • Fat
26
Q

Describe how liquefactive necrosis occurs. How is this different to coagulative?

A

When the release of enzymes (particularly proteases) is greater than protein denaturation dead cells and consequently dead tissue tends to liquefy. In coagulative necrosis there is a greater amount of protein denaturation than enzymes so it results in proteins “clumping”

27
Q

Describe the common histological picture in coagulative necrosis.

A

-Cellular architecture is somewhat preserved
creating a “ghost outline” of the cells
-Increased eosinophilia of cytoplasm

N.b. changes are only seen in the first few days, after that an acute inflammatory response kicks in with phagocytes coming in…fucks all that shit up.

28
Q

Describe the common histological picture in liquefactive necrosis.

A

-Massive neutrophil infiltration (abscess) because
neutrophils release proteases.
-Looks lyse and structure dissapears

29
Q

Describe the common histological picture in caseous necrosis.

A

Caseous is from the word for cheese in latin, so you see an amorphous debris (structureless) with cheese-like white structures.

N.b. you see it commonly in infections (specifically TB) and associated with granulomas

30
Q

In what type of inflammation is fat necrosis commonly seen in? Describe how it occurs in this inflammation?

A

Pancreatitis:

  • Causes release of lipases from injured pancreatic acinar cells.
  • Lipases act on fatty tissue of pancreas and fat elsewhere in the abdominal cavity causing fat necrosis.
  • Fat necrosis causes release of free fatty acids - can react with calcium to form chalky deposits in fatty tissue.
31
Q

Other than pancreatitis suggest when fat necrosis can occur.

A

Direct trauma to fatty tissue.

N.b. in breast tissue this causes a nodule which can be confused with boob cancer..oh no!

32
Q

Define gangrene. What are the two types?

A

Necrosis that is visible to the naked eye, the two types are:

  • Dry (coagulative necrosis)
  • Wet (liquefactive necrosis)
33
Q

Define infarction. What are the two types and why do they occur?

A

Ischaemia that results in necrosis. Two types:

  • Red occurs due to haemorrhage into the necrosed tissue for a number of reasons.
  • White is due to the occlusion of an “end artery” as there is death of the tissue, but, no blood in it.
34
Q

In what situations might a red infarct occur?

A

Infarct occurs where there is extensive haemorrhage into dead tissue which can occur because of:

  • Dual blood supply - one artery is occluded, other one can’t supply it enough to keep it alive, it dies full of blood.
  • Anastomoses - capillary beds of two separate arterial supplies merge, same as above.
  • Loose tissue - poor stromal support for the capillaries causes haemorrhage
  • Previous congestion - in congestive heart failure and the like there is already a build up of blood in the tissue.
  • Raised venous pressure - increased pressure is transmitted to the capillary bed. As the tissue pressure increases this eventually causes reduced arterial filling pressure in the tissue, causing ischaemia and subsequent necrosis. Because the tissue had become engorged with blood we see a red infarct.
35
Q

Give an example of both physiological and pathological apoptosis.

A

Physiological - helps sculpt patterns in embryological development

Pathological - graft versus host disease

36
Q

What are the three stages of apoptosis?

A
  • Initiation
  • Execution
  • Degradation & phagocytosis
37
Q

Suggest some structural changes that can be seen in apoptosis under a light microscope.

A
  • Eosinophilic and dense nuclear fragments
  • Cell shrinkage
  • Chromatin condensation
  • Nuclear fragmentation
  • Phagocytosis by macrophages.
38
Q

Suggest some structural changes that can be seen in apoptosis under a electron microscope.

A
  • Cytoplasmic blebs

- Producing fragmentation into membrane-bound apoptotic bodies (cytoplasm, organelles, +/- nuclear fragments)

39
Q

What are the two ways apoptosis can be initiated.

A
  • Intrinsic pathway

- Extrinsic pathway

40
Q

Describe how apoptosis is initiated by the intrinsic pathway.

A

Mitochondria as a central players. Various triggers for intrinsic apoptosis, notably DNA damage, where apoptosis is heavily influenced by p53. The p53 is activated and therefore increases the mitochondrial permeability, releasing cytochrome C which will interact with APAF1 and procaspase-9 forming the apoptosome. The apoptosome activates caspase-9 kicking off a cascade and apoptosis.

41
Q

Describe how apoptosis is initiated by the extrinsic pathway.

A

A.K.A. receptor-mediated apoptosis is caused by external ligands, such as TRAIL and Fas, that bind to “death receptors”. The binding forms from caspase-8 from procaspase-8 kicking off a cascade and therefore apoptosis.

42
Q

What is the function of the Bcl-2 molecule?

A

Prevents cytochrome c release from mitochondria, therefore inhibits apoptosis.

43
Q

Briefly describe the processes of degradation and phagocytosis in apoptosis

A

-The cell breaks into membrane-bound fragments that are taken up by either neighbouring cells or phagocytes. The microvilli/junctions are lost and there are nuclear changes.
-The membrane bound “apoptotic bodies” express proteins on their surface that are thought to be
essential for phagocytosis by neighbouring cells.

44
Q

Compare the structural changes in necrosis and apoptosis.

A
  • Necrosis is the death of contiguous cells, apoptosis is single cell death
  • The cell is swollen in necrosis and shrunken in apoptosis
  • You get the nuclear changes (pyknosis, karryohexis etc.) in necrosis and nucleosome size fragments in apoptosis
  • There is frequently adjacent inflammation of necrosis and none in apoptosis
  • The plasma membrane is disrupted in necrosis and intact in apoptosis.
45
Q

Describe the metabolism of ethanol by the body.

A
  • Alcohol dehydrogenase (using CYPZE1 and catalase) breaks ethanol down to acetaldehyde (levels of this enzyme are lower in women)
  • Aldehyde dehydrogenase converts acetaldehyde into acetic acid (lower levels in oriental)
46
Q

Describe the biochemical markers of chronic, excessive alcohol intake.

A
  • Elevated MCV (toxic effect on bone marrow or folate deficiency)
  • Raised serum aminotransferase enzymes (AST and ALT) due to hepatocyte leakage
  • Gamma-GT

With alcoholic hepatitis see elevated serum bilirubin, aminotransferases, alkaline phosphatase and PT and occasionally low serum albumin

47
Q

Describe the metabolism of paracetamol (acetaminophen) by the body.

A
  • The majority of it is conjugated (glucuronidation/sulfation) where the complexes will be excreted by the kidneys
  • A small minority of it is metabolised by cytochrome P450 by N-hydroxylation and rearrangement, this forms NAPQI. The NAPQI then undergoes GSH conjugation and is excreted by the kidneys.
48
Q

In what groups of people is paracetamol OD more dangerous? Why?

A
  • Alcohol with the OD
  • Alcohol dependent
  • Malnourished
  • Enzyme-inducing drugs, e.g., carbamazepine
  • HIV positive/AIDS

This is due to a lower reserve of GSH.

49
Q

How does hepatocyte necrosis and liver failure occur in paracetamol overdose?

A

Glutathione is depleted and NAPQI binds with sulphydryl groups on liver cell membranes

50
Q

What is the pharmacological treatment for paracetamol overdose? How do you work out whether it is needed?

A

N-acetylcysteine – increases availability of hepatic glutathione. From 4 hours after OD measure paracetamol serum concentration and the PT or INR (help gage liver damage) this indicates whether specific treatment needs to be started.

51
Q

Describe some of the consequences of aspirin (acetylsalicylic acid) overdose.

A
  • Overdose stimulates respiratory centre resulting in a respiratory alkalosis, then compensatory mechanisms cause metabolic acidosis.
  • Increases ketones, lactate and pyruvate due to interference with these pathways (acidOsis)
  • Can cause erosive gastritis.
  • Inhibits platelet cyclo-oxygenase producing decreased platelet aggregation which results in petechaie.
52
Q

Describe the effects of alcohol abuse on the liver.

A
  • Often results in acute hepatitis, liver cirrhosis and/or “fatty” liver
  • The toxicity results in hepatocyte necrosis, neutrophillic infiltrate, Mallory’s hyaline and lipid in the cell. (steatosis)
  • Also see micronodules of regenerating hepatocytes surrounded by collagen
53
Q

Describe the effects of alcohol abuse on the nervous system.

A
  • Alcohol abuse can result in thiamine deficiency
  • Thiamine deficiency produces degeneration of nerve cells, reactive gliosis, atrophy of cerebellum and peripheral nerves
  • These changes can result in two syndromes (Wernicke and Korsakoff)
54
Q

Describe the effects of alcohol abuse on the cardiovascular system.

A

-Degenerative disease of cardiac muscle causing cardiac dilatation.
-Often results in:
+Cardiomyopathy due to toxicity
+Hypertension due to vasopressor (increased release of catecholamines)
+Cardiac arrhythmias due to thiamine deficiency.
+Beriberi heart disease due to thiamine deficiency.

55
Q

Describe the effects of alcohol abuse on the gastrointestinal system.

A

The toxicity of alcohol abuse can cause gastritis and pancreatitis. (it has -itis it just means inflammation of these areas)

56
Q

What is Korsakoff syndrome?

A

Toxicity and thiamine deficiency resulting in severe memory loss.

57
Q

What is Wernicke syndrome?

A

Thiamine deficiency resulting in ataxia, disturbed cognition, opthalmoplegia and nystagmus

Mechanisms of Disease (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions