Cell Response to Injury: Exogenous injury 1

Question 1

what are the 4 clinical hypoxic states?

Answer 1

• hypoxaemia
• anaemia
• ischaemia
• histoxia

Question 2

what characterises hypoxaemia?

Answer 2

reduced availability of atmospheric O2

Question 3

what characterises anaemia?

Answer 3

reduced O2 capacity of blood

Question 4

what characterises ischaemia?

Answer 4

stagnant circulation

Question 5

what characterises histoxia?

Answer 5

tissues unable to use available O2

Question 6

what causes reperfusion injury?

Answer 6

burst of reactive oxygen species after reoxygenation

Question 7

what happens when a blood vessel ruptures?

Answer 7

blood leaks into CT

Question 8

what phagocytoses the red blood cells?

Answer 8

macrophages

Question 9

what is iron converted into after blood leaks into CT?

Answer 9

brown haemosiderin

Question 10

how can haemorrhages lead to comas?

Answer 10

if there is a haemorrhage in a confined space such as the skull, it means that there is limited space for swelling this causes the pressure to rise and close capillaries resulting in hypoxia and nerve compression = coma

Question 11

what layers of skin are damaged in a first degree burn?

Answer 11

epidermal

Question 12

what layers of skin are damaged in a second degree burn?

Answer 12

epidermal & upper dermis

Question 13

which degree burn means you feel no pain?

Answer 13

third degree and fourth degree

Question 14

what layers of the skins are damages in a third degree burn?

Answer 14

epidermal, dermal, subcutaneous

Question 15

what are the characteristics of fourth degree burns?

Answer 15

epidermal, dermal, subcutaneous; no pain; hair pulls out; ascia, muscle, bone appear blackened, dry; very poorly healing

Question 16

what causes blistering?

Answer 16

separation of epidermal & dermal layers.

Question 17

what are some of the systemic changes that occur after burns?

Answer 17

release of K+ ions → hypervolaemic (burn) shock.

Question 18

what are the 2 ways that cold causes damage?

Answer 18

indirectly – via ischaemia

directly – via freezing of tissues

Question 19

how can cold indirectly cause damages?

Answer 19

• Cooling –> vasoconstriction
• reduction in blood supply –> reduced supply of nutrients to the affected tissues
• return of blood supply
• -> oedema prolonged ischaemia produces necrosis (trench foot)

Question 20

how can cold directly cause damage?

Answer 20

• Freezing of tissues –> frost bite
  (due to ischaemia & direct freezing)
  damage worse, thrombosis occurs in damaged vessels.
• Tissue blackens - erythrocyte leakage

Question 21

what can chemical exposure injuries be due to?

Answer 21

• therapeutic drugs
• industrial chemicals (occupational)
• ‘recreational’ drugs
• environmental chemicals

Question 22

what can harmful effects of chemicals be due to?

Answer 22

• direct action on the cells architecture
• interference with enzyme action
• toxigenesis or metabolic activation (production of toxic compounds from non-toxic ones)
• carcinogenesis

Question 23

what is an example of the direct action of chemicals on cell structure?

Answer 23

lead poisoning

Question 24

how can lead affect cell structure?

Answer 24

Can join nearby sulphydryl and carboxyl groups in peptides

& proteins so interfere with enzyme action & protein conformation

Question 25

which enzymes do chemicals interfere with?

Answer 25

enzymes for generating essential | products and/or removing toxic substrates

Question 26

what chemicals have direct actions on proteins?

Answer 26

- lead | - corrosive agents that inactivate enzymes by stabilising protein structure eg, formaldehyde, mercury

Question 27

how does carbon monoxide cause injury?

Answer 27

Carbon monoxide: competes with O2 for haemoglobin and is bound more firmly than O2 → inhibits O2 blood transport → hypoxia Also, binds Fe++ in cytochrome oxidase in cells and so reduces cellular O2 absorption

Question 28

what is competitive inhibition?

Answer 28

Toxin competes with substrate.

Question 29

what are examples of toxins that use competitive inhibition?

Answer 29

- fluorocitrate | - Folate antagonists

Question 30

what is fluorocitrate?

Answer 30

Structural analogue of citrate

Question 31

what does fluorocitrate inhibit?

Answer 31

cis-aconitase. Thus inhibits use of citrate in TCA cycle.

Question 32

what do folate antagonists inhibit?

Answer 32

DNA synthesis.

Question 33

how is thymine synthesis blocked?

Answer 33

via inhibition of Dihydrofolate reductase.

Question 34

what is an example of Steric exclusion of enzyme from site of action?

Answer 34

Actinomycin High affinity for DNA. Binds guanosine residues by intercalating planar rings between adjacent base-pairs. Thus inhibits RNA polymerase & transcription.

Question 35

where are microsomal oxygenases found?

Answer 35

mainly in the endoplasmic reticulum of liver cells but most other types

Question 36

what are microsomal oxygenases dependent of?

Answer 36

oxygen, NADDPH & cytochrome P450

Question 37

what are the substrates of microsomal oxygenases?

Answer 37

aromatic hydrocarbons, CCl4, aromatic amines

Question 38

what happens to the substrates of microsomal oxygenases?

Answer 38

metabolised into reactive species, which react with macromolecules

Question 39

what is an example of a microsomal oxygenase effect?

Answer 39

carbon tetrachloride (CCl4) Hepatotoxin --> necrosis & fatty globulation --> cirrhosis in central zone of hepatic lobule. Involves swelling of ER cisternae & mitochondria, degranulation & rER ribosome loss

Question 40

where is the site of cancers for polycyclic hydrocarbons?

Answer 40

skin scrotum

Question 41

where is the site of cancers for aromatic amines?

Answer 41

bladder

Question 42

where is the site of cancers for aflatoxins?

Answer 42

liver

Question 43

where is the site of cancers for nitrosamines?

Answer 43

stomach, oesophagus

Question 44

where is the site of cancers for chemotherapy agents?

Answer 44

leukaemias

Question 45

where is the site of cancers for asbestos?

Answer 45

lung mesothelioma

Question 46

where is the site of cancers for heavy metals?

Answer 46

lung

Question 47

what is the mode of action for many carcinogens?

Answer 47

usually DNA damage through: - Base alkylation - Strand breaks - Cross-linkages - Cellular DNA repair may → mutation eg, insertion/deletion, base substitution

Question 48

what are the non-genotoxic mechanisms of carcinogens?

Answer 48

- Change growth regulatory proteins - Synergy with viruses (depressing anti-oncogene activity) - Promoters of other toxins/carcinogens

Question 49

what are the primary causes of nutritional deficiencies?

Answer 49

Inadequate food intake (malnutrition) Eg, food shortages, poverty, age, alcoholism

Question 50

what are the secondary causes of nutritional deficiencies?

Answer 50

Malnutrition despite sufficient nutrients: Failure of intestinal absorption → deficiency of specific nutrient (eg, vit B12 in pernicious anaemia) Increased metabolic demand → increased demand for specific nutrient eg, folic acid in pregnancy Antagonists eg folic acid antagonists like Methotrexate

Question 51

what are causes of nutritional excess?

Answer 51

Obesity – excessive intake of cholesterol, saturated fats can lead to atherosclerosis

Question 52

what is an example of microbes causing nutrient deprivation?

Answer 52

Cornebacterium diptheriae infection → membrane over larynx obstructs breathing. leads to problems with the absorption of oxygen

Question 53

how do microbes cause injury through the production of toxins?

Answer 53

Clostridium botulinum: toxin prevents release of acetyl choline which leads to paralysis and death Vibrio cholerae: toxin acts upon adenyl cyclase --> enterocytes secrete large amounts fluid which leads to dehydration

Question 54

what is an example of microbes causing injury through antigenicity?

Answer 54

Mycobacterium tuberculosis | Products produce damaging antigenic response. Eg, lipids of cell walls & cytoplasmic proteins

Question 55

what is an example of microbes causing injury through intercellular growth?

Answer 55

Neisseria gonorrhoeae/N. meningitidis attract & survive in phagocytic neutrophils. Cells fill with bacteria --> neutrophil death --> necrosis --> pyrogenic inflammation.

Question 56

how can radiation cause injury through direct action?

Answer 56

alters/inactivates cell molecules DNA, RNA etc

Question 57

how can radiation cause injury through indirect action?

Answer 57

ionisation of intra-cellular water --> reactive free radicals