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ESA2 - Mechanisms Of Disease > Cell Injury > Flashcards

Cell Injury Flashcards

1
Q

What does the degree of cell damage depend on?

A
  • Nature of injury
  • Duration of injury
  • Severity of injury
  • Type of tissue
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2
Q

In disease where does the ultimate abnormality lie?

A

In the cell

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3
Q

What are the main causes of cell injury? (7)

A
  • Hypoxia
  • Microorganisms
  • Physical agents (temperature, trauma)
  • Chemical agents (drugs, poisons)
  • Autoimmune reactions
  • Diet insufficiencies/excess
  • Genetic abnormalities
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4
Q

What is the difference between hypoxia and ischaemia?

A
  • Hypoxia is OXYGEN DEPRIVATION of tissues and ischaemia is LOSS OF BLOOD SUPPLY to tissues
  • Ischaemia can cause hypoxia as lack of blood supply leads to O2 deprivation
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5
Q

What are the 4 causes of hypoxia?

A
  • HYPOXAEMIC - arterial content of O2 is low (altitude, lung disease)
  • ANAEMIC - decreased carrying capacity of Hb (anaemia, CO)
  • ISCHAEMIC - loss of blood supply (heart failure, blockage)
  • HISTIOCYTIC - disabled oxidative phosphorylation (CN-)
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6
Q

Why can the length of time that a cell can tolerate hypoxia vary?

A

Different cells have different tolerance levels e.g. NEURONES can only tolerate a few minutes, whereas DERMAL FIBROBLASTS can tolerate hours

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7
Q

List 3 physical agents that can cause cell injury

A
  • Extreme temperature
  • Direct trauma
  • Radiation
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8
Q

Describe 2 ways in which immune mechanisms can cause cell injury

A
  • HYPERSENSITIVITY REACTIONS where host tissue is injured secondary to an immune reaction
  • AUTOIMMUNE REACTION where immune system fails to distinguish between self and non-self cells
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9
Q

List 3 chemical agents that can cause cell injury

A
  • Poisons
  • Alcohol/illicit drugs
  • Oxygen in high concentrations
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10
Q

What cell components are the primary targets for cell injury?

A
  • Plasma membrane
  • Nucleus
  • Proteins
  • Mitochondria
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11
Q

Why are proteins considered a primary target for cell injury?

A
  • Proteins have many structural and metabolic roles within the cell
  • They form the cytoskeleton and enzymes involved in metabolic processes within the cell
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12
Q

When does the cell become fully compromised to cell injury following oxygen deprivation?

A
  • When intracellular ATP concentrations drop to 5-10% of the norm
  • ATP is needed for the majority of metabolic processes that occur in cells so decrease in ATP leaves vital processes compromised
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13
Q

What is pathology?

A

The study of disease and cellular malfunction, investigating the structural and functional changes that occur in the cell during disease

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14
Q

Define ‘oncosis’ and explain how this occurs

A
  • Oncosis is CELL DEATH WITH SWELLING
  • When intracellular ATP is low, the Na+/K+ pump cannot function
  • This results in an influx of Na+ which draws water with it causing the cell and organelles to swell
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15
Q

Explain the changes that occur AFTER ONCOSIS of the cell following injury

A
  • Ca2+ enters cell/released from stores in mitochondria and ER
  • Activates a number of enzymes (such as phospholipases, endonucleases, proteases and ATPases) which cause damage to cell components
  • Digestive enzymes leak out of lysosomes and cause further damage
  • Blebbing occurs, followed by cell death
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16
Q

When does cell injury become irreversible?

A
  • Decreased ATP production due to O2 deprivation affects the action of the protein channels in the plasma membrane and therefore the integrity
  • Loss of membrane integrity (following oncosis) leads to an influx of Ca2+ into the cell which activates potent enzymes that cause irreversible damage
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17
Q

Briefly describe how free radicals can cause cell injury

A
  • Cause lipid peroxidation (formation of lipid radicals) which can lead to loss of membrane integrity
  • Cause crosslinking and denaturing of proteins
  • Cause damage to DNA and increase risk of genetic mutations
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18
Q

What defence mechanisms does the body have to protect against free radicals?

A
  • ENZYMES such as superoxide dismutase and catalase

- ANTIOXIDANTS such as glutathione and free radical scavengers (vitamins A, C and E)

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19
Q

What are free radicals (ROS)?

A

Molecules with a SINGLE UNPAIRED ELECTRON that can cause oxidative damage

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20
Q

What happens to ribosomes when intracellular ATP levels are low and what is the sequela?

A
  • Ribosomes detach from ER into cytoplasm as ATP is required for them to be attached
  • Protein synthesis is compromised which leads to an accumulation of fats and denatured proteins (as enzymatic pathways cannot occur)
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21
Q

Define ‘necrosis’

A

The morphological changes that take place after a cell has been dead for some time - changes in appearance occur due to progressive degradation of injured cell by enzymes

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22
Q

How could you detect damage to certain cells/tissues using a blood test?

A
  • As cells lose membrane integrity upon injury, intracellular substances leak out into circulation
  • Detection of these could indicate damage to specific tissues e.g. Troponin is released by cardiac myocytes upon damage; hepatocytes release transaminases ALT and AST
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23
Q

Name a secondary cause of damage to the cell due to lack of oxygen and ATP

A
  • Lack of oxygen activates anaerobic (glycolytic) pathway
  • Increased production of LACTATE decreased the intracellular pH which affects the function of many proteins and ‘chromatin clumping’ occurs
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24
Q

What is meant by ‘ischaemic-reperfusion injury’?

A

When blood flow is returned to a tissue that has been subjected to ischaemia but ISN’T NECROTIC, the tissue injury is sometimes worsened that if the blood supply had not been restored

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25
Q

Explain 3 ways in which ischaemia-reperfusion can worsen cell injury

A
  • Increased production of ROS SPECIES upon reoxygenation
  • Increased number of NEUTROPHILS as blood is reinstated, resulting in more inflammation and increased tissue injury
  • Delivery of COMPLEMENT PROTEINS and activation of the complement pathway
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26
Q

Give one example of a chemical that can cause cell injury and briefly explain how this occurs

A
  • CYANIDE
  • Binds to cellular components (mitochondrial cytochrome oxidase) and inhibits oxidative phosphorylation
  • Lack of ATP production begins the pathway of cell damage and death
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27
Q

Why could we not live without free radicals?

A
  • Produced by leukocytes and are released to kill bacteria

- Role in cell signalling

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28
Q

Name 3 free radicals produced by the body

A
  • Superoxide O2-
  • Hydrogen peroxide H2O2
  • HYDROXYL OH-
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29
Q

Name 2 ways in which dangerous hydroxyl OH- free radicals can be formed

A
  • RADIATION can directly lyse water to form OH-
  • FENTON reaction which forms OH- from Fe2+ and H2O2
  • HABER-WEISS reaction which forms OH- from superoxide and H2O2
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30
Q

What is a heat shock protein? Explain their role and give one example

A
  • HSPs recognise proteins that have been mis-folded or damaged during cell injury and repair them
  • They play a key role in MAINTAINING PROTEIN VIABILITY DURING CELL INJURY
  • An example of a HSP is Ubiquitin
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31
Q

Explain how cytoplasmic changes identified using a light microscope can help to identify injured cells

A
  • Reduced pink staining of cytoplasm due to accumulation of water (reversible)
  • Followed by increased pink staining due to detachment and loss of ribosomes from ER and accumulation of denatured proteins (irreversible)
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32
Q

Describe the visible nuclear changes that occur during IRREVERSIBLE cell injury

A
  • PYKNOSIS (shrinkage)
  • KARRYOHEXIS (fragmentation)
  • KARRYOLYSIS (dissolution)
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33
Q

Name one reversible nuclear change that occurs following cell injury

A

CHROMATIN CLUMPING due to reduced intracellular pH

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34
Q

List 4 reversible changes that occur during cell injury

A
  • CELL SWELLING due to failure of ionic pumps
  • CYTOPLASMIC BLEBS due to cell swelling
  • CHROMATIN CLUMPING due to reduced pH
  • RIBOSOME SEPARATION FROM ER due to lack of ATP
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35
Q

List 4 irreversible changes that occur during cell injury

A
  • Nuclear changes such as pyknosis, karryohexis and karryolysis
  • Swelling and rupture of lysosomes
  • Membrane defects and lysis of ER
  • Amorphous densities in swelled mitochondria
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36
Q

When does necrosis occur?

A

4-24 hrs after cell death (oncosis)

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37
Q

What is the difference between coagulative and liquifactive necrosis?

A
  • COAGULATIVE - proteins undergo denaturation and coagulate/clump. Dead tissue is solid
  • LIQUIFACTIVE - proteins undergo dissolution by cells own enzymes (proteases). Dead tissue liquifies
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38
Q

Describe how coagulative necrosis occurs and state the appearance of the tissue

A
  • DENATURATION OF PROTEINS DOMINATES OVER RELEASE OF ACTIVE PROTEASES
  • Dead tissue has a SOLID appearance and is WHITE
  • Cell architecture is preserved creating a “GHOST OUTLINE” after a few days
  • Appearance is modified following acute inflammatory response and phagocytosis
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39
Q

What type of necrosis is commonly seen in tissues with massive neutrophil infiltration (e.g. Abscesses) and why?

A
  • LIQUIFACTIVE
  • Neutrophils release PROTEASES so active enzyme degradation is substantially greater than denaturation, leading to enzymatic digestion
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40
Q

What tissues are more susceptible to liquifactive necrosis, rather than coagulative and why?

A
  • Tissues such as BRAIN and LUNGS
  • Tissues are fragile and have NO SUPPORT from a collagenous matrix
  • Dead tissue is a viscous mass and if acute inflammation occurs, PUS is present
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41
Q

Describe the appearance of a tissue that has undergone caseous necrosis

A
  • “Cheesy appearance” with amorphous (structure less) debris
  • Granulomatous inflammation
  • No “ghost outline”
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42
Q

Which microbial infection may give rise to caseous necrosis?

A

TUBERCULOSIS

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43
Q

Describe how fat necrosis occurs following acute pancreatitis

A
  • Release of pancreatic LIPASES from damaged pancreatic acinar cells of the inflamed pancreas
  • Lipases act on fatty tissue causing fat necrosis and release of free fatty acids
  • Fatty acids can calcify forming chalky deposits known as CALCIUM SOAPS or “taches de bougie”
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44
Q

Explain how fat necrosis can be mistaken for breast cancer

A
  • Fat necrosis can occur after direct trauma to fatty tissue in breast
  • Once healed, it leaves an IRREGULAR SCAR which can mimic a nodule of breast cancer
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45
Q

What is gangrene?

A
  • NOT A TYPE OF NECROSIS
  • Necrosis that is visible to the naked eye
  • Can have DRY or WET gangrene
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46
Q

Describe the differences in dry and wet gangrene

A
  • DRY - tissue is left exposed to air and becomes dehydrated so bacteria cannot infiltrate (results from coagulative necrosis)
  • WET - tissue is infected by bacterial culture which can infiltrate circulation and cause septicaemia (results from liquifactive necrosis)
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47
Q

What is gas gangrene? Give one example of how this may occur

A
  • WET GANGRENE where tissue has become infected by ANAEROBIC BACTERIA which produce palpable bubbles of gas within the tissues
  • Occurs during crushing of a limb in a motorcycle accident (injured tissue loses blood supply, becomes necrotic and picks up bacteria from soil)
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48
Q

Define ‘infarction’ in its simplest terms

A

Necrosis due to ischaemia

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49
Q

What is an ‘infarct’?

A
  • Area of tissue death (necrosis) caused by obstruction of a tissues blood supply (ischaemia)
  • Most infractions are due to thrombosis or embolism
50
Q

List 4 occurrences that can cause an infarct

A
  • THROMBOSIS (blockage of vessel by a thrombus)
  • EMBOLISM (blockage by embolus/fragment of thrombus)
  • EXTERNAL COMPRESSION of a vessel (by tumour/within hernia)
  • TWISTING of vessel (testicular torsion)
51
Q

Give examples of coagulative and liquifactive necrosis caused by ischaemia

A
  • MYOCARDIAL INFARCTION is ischaemic necrosis of the heart and is coagulative
  • CEREBRAL INFARCTION is ischaemic necrosis of the brain and is liquifactive
52
Q

Describe the formation of a white infarct and give examples of organs where this may occur

A
  • OCCLUSION OF AN END ARTERY in ‘solid’ organs, causing ischaemia and coagulative necrosis
  • Solid nature of dead tissue limits the amount of haemorrhage
  • Tissue appears white due to lack of blood supply
  • Occurs in the HEART, SPLEEN and KIDNEYS; appear wedge-shaped with occluded artery at the apex
53
Q

What causes a red infarct to appear red?

A

Extensive haemorrhage into dead tissue

54
Q

Give 5 examples of where a red infarct may occur

A
  • Organs with a dual blood supply
  • Organs with numerous anastomoses
  • Loose tissues which do not have a collagenous support (lungs)
  • Where venous pressure is increased
  • Where there has been previous conjestion
55
Q

Explain how increased venous pressure can lead to a red infarct

A
  • Increased pressure transmitted to capillary bed
  • Tissue pressure increases so there is reduced arterial filing pressure, causing ischaemia and necrosis
  • Tissue is engorged in blood therefore infarct is red
56
Q

Why do organs with dual blood supplies cause red infarcts?

A
  • Occlusion of the main arterial supply causes an infarct
  • Secondary arterial supply is insufficient to rescue the tissue but still allows blood to flow, causing haemorrhage and red infarct
57
Q

What do the consequences of infarcts depend on?

A
  • Whether tissue has a dual blood supply
  • How quickly ischaemia occurs (if slow, alternative perfusion can develop)
  • How vulnerable tissue is to hypoxia
  • Oxygen content of blood (anaemic patients experience more damage)
58
Q

What are the consequences of molecules leaking out of injured cells?

A
  • May have general toxic effects on body
  • May cause local irritation or inflammation
  • Appear in high concentrations in the blood so can be measured and used to aid diagnosis
59
Q

What is the significance of the release of potassium from an injured cell?

A
  • High concentrations of potassium can cause the heart to stop
  • Potassium solution is used to keep the heart still during surgery
60
Q

Explain how high potassium concentrations can reach the heart and cause it to stop

A
  • Myocardial infarction

- Massive necrosis elsewhere in the body (severe burns, tourniquet shock and tumour lysis syndrome)

61
Q

Name 3 principle molecules that are released from cell membranes following damage

A
  • Potassium
  • Enzymes (transaminases, troponin)
  • Myoglobin
62
Q

How can enzymes in the plasma be used as a useful diagnostic tool in determining cell injury?

A
  • Enzymes that are released into the plasma following cell injury would normally be intracellular and can be detected in blood tests
  • Indicates organ involved, timing and evolution of the tissue damage
  • e.g. Troponin is released following MI but can only be detected 20mins straight after the occurrence
63
Q

What is the significance of myoglobin release following cell membrane injury?

A
  • Released from dead myocardium or damaged striated muscle, causes rhabdomylosis from burns/trauma, potassium depletion or drug abuse
  • Can plug renal tubules and cause renal failure
64
Q

Define ‘apoptosis’

A
  • CELL DEATH WITH SHRINKAGE

- Physiological death of a single cell due to activation of regulated intracellular enzymatic reactions

65
Q

What are ‘caspases’ and what is their cellular function?

A
  • Proteases that are activated and mediate the cellular effects of apoptosis
  • Act by breaking up cytoskeleton, cleaving proteins and initiating DNA degradation
66
Q

Explain 3 ways in which apoptosis differs from oncosis/necrosis under a microscope

A
  • In apoptosis the membrane integrity is maintained and there is no leakage or inflammation
  • Apoptosis results in cell shrinking, not swelling
  • In apoptosis, the chromatin condenses and there is no karyolysis of DNA, budding occurs and formation of apoptotic bodies
67
Q

What is the difference between intrinsic and extrinsic apoptosis?

A
  • INTRINSIC occurs as a result of increased permeability of mitochondrial membrane leading to leakage of proteins and activation of enzymes
  • EXTRINSIC occurs due to binding of external ligands to “death receptors” which activate enzymes
68
Q

Describe the process of intrinsic apoptosis and the enzymes involved

A
  • p53 mediates apoptosis in response to DNA damage
  • Increased permeability of mitochondria leads to leakage of cytochrome c, which interacts the APAF1 and Caspase9 which form an APOPTOSOME which activates various downstream caspases
69
Q

Describe the process of extrinsic apoptosis

A
  • Receptor mediated by binding of external ligands such as TRAIL and Fas to “death receptors”
  • Leads to activation of Caspase8 and other caspases independently of mitochondria
70
Q

What is the role of Bcl-2?

A

INHIBITS INTRINSIC APOPTOSIS by preventing the release of cytochrome c from the mitochondria

71
Q

Describe the degradation stage of apoptosis

A
  • Budding of cell membrane and contents produces APOPTOTIC BODIES
  • These are phagocytosed by neighbouring cells or phagocytes (macrophages)
72
Q

Name 5 abnormal cellular accumulations that can occur following cell injury

A
  • Water and electrolytes
  • Lipids
  • Proteins
  • Carbohydrates
  • Pigments
73
Q

What is meant by ‘hydroptic swelling’?

A
  • Cell swelling due to osmotic disturbances
  • Occurs when ATP production is insufficient for function of ion channels, leading to an influx of Na+ into cell and water follows
  • Cells are enlarged but NOT HYPERTROPHIC
74
Q

Explain how cell swelling can cause further problems in certain parts of the body

A
  • In BRAIN cell swelling causes tissue to expand
  • No room for expansion due to skull
  • COMPRESSION occurs, blood vessels are squeezed and blood supply to brain is reduced
75
Q

What is ‘steatosis’ and where might this occur in the body?

A
  • Accumulation of TAGs in cells and tissues due to cell injury
  • Commonly seen in the LIVER (major organ of fat metabolism) caused by alcohol abuse, DM, obesity and toxins such as carbon tetrachloride
76
Q

How might the liver appear in advanced steatosis?

A
  • Golden yellow in colour
  • Enlarged
  • When cut, knife is covered in grease
77
Q

What is steatosis a sign of?

A

ALCOHOLIC LIVER DISEASE

78
Q

Describe 2 ways in which an accumulation of cholesterol can cause visible effects on cell structures

A
  • Accumulation of cholesterol in smooth muscle cells and macrophages of vessels can lead to FOAM CELLS which form atherosclerotic plaques
  • Accumulation in skin and tendons during Hyperlipidaemia can cause xanthoma, xanthelasma or corneal arcus
79
Q

How may accumulated proteins appear in damaged cells?

A
  • Eosinophilic droplets

- Aggregates within cytoplasm

80
Q

Explain how α1-antitrypsin deficiency can lead to emphysema of the lungs

A
  • Liver produces incorrectly folded version of α1-antitrypsin that cannot be packaged by ER
  • ACCUMULATION within ER and cannot be secreted
  • PROTEASES act in lung unchecked which can lead to damage and breakdown of lung tissue
81
Q

Give two examples of exogenous pigments that can accumulate in cells

A
  • CARBON/SOOT in coal-workers pneumoconiosis where coal dust is phagocytosed and leads to BLACKENED LUNGS which can become fibrotic or emphysematous
  • TATTOOING where pigments in skin can be phagocytosed by macrophages or enter lymph nodes
82
Q

Give 3 examples of endogenous pigments that can accumulate in cells

A
  • BILIRUBIN (breakdown of Hb in RBC lysis)
  • LIPOFUSCIN (from previous lipid peroxidation)
  • HAEMOSIDERIN (iron storage molecule derived from Hb)
83
Q

What is the appearance of LIPOFUSCIN in cells?

A
  • YELLOW/BROWN GRAINS in cytoplasm

- Seen in ageing/long lived cells (myocardium) but not in those with a high turnover (epithelia)

84
Q

Give an example of how local overload of iron and haemosiderin can be seen

A
  • HAEMORRHAGE of skin or subcutaneous tissue

- BRUISING

85
Q

What is ‘haemosiderosis’ and how can this be caused?

A
  • SYSTEMIC OVERLOAD OF IRON into tissues or organs

- Caused by haemolytic anaemia, blood transfusion and hereditary haemochromatosis

86
Q

What are the effects of haemochromatosis and how is this treated?

A
  • Iron deposits (skin, liver, pancreas, heart, endocrine) which can lead to SCARRING, DYSFUNCTION and FAILURE of organs
  • Treated by REPEATED BLEEDING
87
Q

What is ‘bilirubin’ and how can it accumulate?

A
  • Stack of polyphyrin rings that have lost their iron (heme) and is a BRIGHT YELLOW PIGMENT
  • If levels rise (due to obstruction or overwhelming of bile flow) this can cause JAUNDICE
  • Can be formed anywhere in the body as all cells contain heme in cytochromes
88
Q

Briefly describe the formation and excretion of bilirubin

A
  • Heme groups broken down and iron is lost, forming BILIVERDIN which is harmless
  • Biliverdin is broken down into bilirubin which is VERY TOXIC
  • Transported from tissues to liver via albumin to be CONJUGATED as excreted in the bile
89
Q

Define ‘apoptosis’

A
  • CELL DEATH WITH SHRINKAGE

- Physiological death of a single cell due to activation of regulated intracellular enzymatic reactions

90
Q

What are ‘caspases’ and what is their cellular function?

A
  • Proteases that are activated and mediate the cellular effects of apoptosis
  • Act by breaking up cytoskeleton, cleaving proteins and initiating DNA degradation
91
Q

Explain 3 ways in which apoptosis differs from oncosis/necrosis under a microscope

A
  • In apoptosis the membrane integrity is maintained and there is no leakage or inflammation
  • Apoptosis results in cell shrinking, not swelling
  • In apoptosis, the chromatin condenses and there is no karyolysis of DNA, budding occurs and formation of apoptotic bodies
92
Q

What is the difference between intrinsic and extrinsic apoptosis?

A
  • INTRINSIC occurs as a result of increased permeability of mitochondrial membrane leading to leakage of proteins and activation of enzymes
  • EXTRINSIC occurs due to binding of external ligands to “death receptors” which activate enzymes
93
Q

Describe the process of intrinsic apoptosis and the enzymes involved

A
  • p53 mediates apoptosis in response to DNA damage
  • Increased permeability of mitochondria leads to leakage of cytochrome c, which interacts the APAF1 and Caspase9 which form an APOPTOSOME which activates various downstream caspases
94
Q

Describe the process of extrinsic apoptosis

A
  • Receptor mediated by binding of external ligands such as TRAIL and Fas to “death receptors”
  • Leads to activation of Caspase8 and other caspases independently of mitochondria
95
Q

What is the role of Bcl-2?

A

INHIBITS INTRINSIC APOPTOSIS by preventing the release of cytochrome c from the mitochondria

96
Q

Describe the degradation stage of apoptosis

A
  • Budding of cell membrane and contents produces APOPTOTIC BODIES
  • These are phagocytosed by neighbouring cells or phagocytes (macrophages)
97
Q

Name 5 abnormal cellular accumulations that can occur following cell injury

A
  • Water and electrolytes
  • Lipids
  • Proteins
  • Carbohydrates
  • Pigments
98
Q

What is meant by ‘hydroptic swelling’?

A
  • Cell swelling due to osmotic disturbances
  • Occurs when ATP production is insufficient for function of ion channels, leading to an influx of Na+ into cell and water follows
  • Cells are enlarged but NOT HYPERTROPHIC
99
Q

Explain how cell swelling can cause further problems in certain parts of the body

A
  • In BRAIN cell swelling causes tissue to expand
  • No room for expansion due to skull
  • COMPRESSION occurs, blood vessels are squeezed and blood supply to brain is reduced
100
Q

What is ‘steatosis’ and where might this occur in the body?

A
  • Accumulation of TAGs in cells and tissues due to cell injury
  • Commonly seen in the LIVER (major organ of fat metabolism) caused by alcohol abuse, DM, obesity and toxins such as carbon tetrachloride
101
Q

How might the liver appear in advanced steatosis?

A
  • Golden yellow in colour
  • Enlarged
  • When cut, knife is covered in grease
102
Q

What is steatosis a sign of?

A

ALCOHOLIC LIVER DISEASE

103
Q

Describe 2 ways in which an accumulation of cholesterol can cause visible effects on cell structures

A
  • Accumulation of cholesterol in smooth muscle cells and macrophages of vessels can lead to FOAM CELLS which form atherosclerotic plaques
  • Accumulation in skin and tendons during Hyperlipidaemia can cause xanthoma, xanthelasma or corneal arcus
104
Q

How may accumulated proteins appear in damaged cells?

A
  • Eosinophilic droplets

- Aggregates within cytoplasm

105
Q

Explain how α1-antitrypsin deficiency can lead to emphysema of the lungs

A
  • Liver produces incorrectly folded version of α1-antitrypsin that cannot be packaged by ER
  • ACCUMULATION within ER and cannot be secreted
  • PROTEASES act in lung unchecked which can lead to damage and breakdown of lung tissue
106
Q

Give two examples of exogenous pigments that can accumulate in cells

A
  • CARBON/SOOT in coal-workers pneumoconiosis where coal dust is phagocytosed and leads to BLACKENED LUNGS which can become fibrotic or emphysematous
  • TATTOOING where pigments in skin can be phagocytosed by macrophages or enter lymph nodes
107
Q

Give 3 examples of endogenous pigments that can accumulate in cells

A
  • BILIRUBIN (breakdown of Hb in RBC lysis)
  • LIPOFUSCIN (from previous lipid peroxidation)
  • HAEMOSIDERIN (iron storage molecule derived from Hb)
108
Q

What is the appearance of LIPOFUSCIN in cells?

A
  • YELLOW/BROWN GRAINS in cytoplasm

- Seen in ageing/long lived cells (myocardium) but not in those with a high turnover (epithelia)

109
Q

Give an example of how local overload of iron and haemosiderin can be seen

A
  • HAEMORRHAGE of skin or subcutaneous tissue

- BRUISING

110
Q

What is ‘haemosiderosis’ and how can this be caused?

A
  • SYSTEMIC OVERLOAD OF IRON into tissues or organs

- Caused by haemolytic anaemia, blood transfusion and hereditary haemochromatosis

111
Q

What are the effects of haemochromatosis and how is this treated?

A
  • Iron deposits (skin, liver, pancreas, heart, endocrine) which can lead to SCARRING, DYSFUNCTION and FAILURE of organs
  • Treated by REPEATED BLEEDING
112
Q

What is ‘bilirubin’ and how can it accumulate?

A
  • Stack of polyphyrin rings that have lost their iron (heme) and is a BRIGHT YELLOW PIGMENT
  • If levels rise (due to obstruction or overwhelming of bile flow) this can cause JAUNDICE
  • Can be formed anywhere in the body as all cells contain heme in cytochromes
113
Q

Briefly describe the formation and excretion of bilirubin

A
  • Heme groups broken down and iron is lost, forming BILIVERDIN which is harmless
  • Biliverdin is broken down into bilirubin which is VERY TOXIC
  • Transported from tissues to liver via albumin to be CONJUGATED as excreted in the bile
114
Q

What is ‘dystrophic calcification’ and where might this occur?

A
  • Local change or disturbance in tissues favours NUCLEATION OF HYDROXYAPATITE CRYSTALS
  • No change in calcium metabolism or serum Ca2+/K+ concentration
  • Occurs in dying tissue, heart valves (not pulmonary), tuberculous lymph nodes and atherosclerotic plaques
115
Q

How does metastatic calcification differ from dystrophic?

A
  • Metastatic is body-wide whereas dystrophic is localised
  • Hydroxyapitate crystals are deposited in normal tissues where there is HYPERCALCAEMIA secondary to disturbances in calcium metabolism
116
Q

Describe 2 ways which hypercalcaemia can occur, leading to metastatic calcification

A
  • Increased secretion of PTH and bone reabsorption by parathyroid tumour, ectopic secretion of PTHrp or renal failure (increased Pi absorption)
  • Destruction of bone tissue by bone marrow tumour, diffusion of skeletal metastases, Paget’s disease or immobilisation
117
Q

Describe the process of cell ageing

A
  • Accumulations of damage to organelles/DNA, denatured proteins and lipofuscin
  • REPLICATION SENESCENCE where telomeres shorten as cells age and replicate (cells lose their ability to divide)
118
Q

Why can some cells (such as stem cells and germ cells) continue to replicate indefinitely?

A
  • Contain TELOMERASE
  • Maintains the length of the telomeres so cells can continue to replicate without senescence
  • Telomerase is also produced by CANCER CELLS
119
Q

Name 3 effects of chronic excessive alcohol consumption on the liver

A
  • LIVER STEATOSIS (alcohol affects fat metabolism, causing steatosis and hepatomegaly, reversible)
  • ACUTE ALCOHOLIC HEPATITIS (toxic metabolites produced from alcohol can cause focal hepatocyte necrosis, reversible)
  • CIRRHOSIS (hardening of liver and scarring, irreversible)
120
Q

Explain the pathophysiology of acute alcoholic hepatitis

A
  • Excessive consumption of alcohol leads to build up of toxic metabolites
  • Causes ACUTE HEPATITIS with focal necrosis, Mallory body formation and infiltration of neutrophils
  • Symptoms include fever, jaundice and liver tenderness. Often reversible
121
Q

Describe one irreversible effect of chronic excessive alcohol consumption on the liver

A
  • CIRRHOSIS
  • Appears as hard, shrunken liver with micronodules of regenerating hepatocytes surrounded by bands of collagen
  • Damage is irreversible and can be fatal
122
Q

Give examples of pathological and physiological apoptosis

A
  • PATHOLOGICAL - viral hepatitis, toxic injury or tumour

- PHYSIOLOGICAL - embryogenesis and development of limbs (interdigitation)

ESA2 - Mechanisms Of Disease (8 decks)

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