Brainscape's Knowledge GenomeTM

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


See full index

Mechanisms of Disease > 1&2) Cell Injury > Flashcards

1&2) Cell Injury Flashcards

0
Q

Define hypoxia?

Toleration of cell types?

A

Reduced O2 causing decreased oxidative respiration, cell adaptation occurs leading to cell injury and death
Neurones: last minutes
Dermal fibroblasts: hours

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

Causes of cell injury/death? (8)

A 
Hypoxia
Toxins
Heat
Cold
Trauma
Radiation
Micro organisms
Immune mechanisms e.g Hypersensitivity and Autoimmune
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define Ischaemia?

A

Loss of blood supply due to lowered arterial supply or venous drainage
Lowers oxygen and metabolites reaching the tissue

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

Types of hypoxia? (4)

A

Hypoxaemic - arterial content of oxygen is low e.g high altitude
Anaemic - decreased ability of Hb to carry oxygen e.g CO poisoning
Ischaemia - interrupted blood supply e.g blockage of vessel
Histiocytic - unable to use O2, disabled ox. phosphorylation e.g CN poisoning

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

Targets of cell injury? (4)

A

Membranes - cell itself and organelles e.g lysosomes release hydrolases
Nucleus - contains genetic info
Mitichondria - used for ox. phosphorylation
Proteins - structural and metabolic

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

Reversible hypoxia injury? (3)

A

Low Ox. phosphorylation - low ATP, stops Na+/K+ pump, high Na+ in the cell, draws in water by osmosis, causes swelling
High anaerobic glycolysis - low pH, increased lactate, chromatin clumps
Ribosomes detach from ER - lowers protein synthesis and increased Intracellular substances e.g fat

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

Electron microscopic changes due to reversible hypoxia? (5)

A 
Autophagy
Swelling
Ribosome dispersal
Chromatin clumps 
Blebs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Irreversible hypoxia? (2)

A
  • Increased cytosolic accumulation of Ca 2+ via reversed NCX

- Several enzymes activated causing cell death e.g proteases, nucleases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Electron microscopic changes due to irreversible hypoxia? (4)

A
  • Nuclear changes - Pyknosis (shrinkage), karryohexis (fragmentation), karryolysis (dissolution)
  • Lysosomes rupture
  • ER lysis
  • Myelin figures (membrane defects)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Effects of Cyanide poisoning causing histiocytic hypoxia?

A

Binds to mitochondria cytochrome oxidase which blocks oxidative phosphorylation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain ischaemic reperfusion injury?

A

Returning blood flow to tissue affected by Ischaemia causes further damage due to

1) Increased O2 = increased free radicals
2) Increased neutrophils = further inflammation and tissue injury
3) Delivers complement proteins = complement process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Define free radicals?

When are they produced, what do they attack and what are they used for?

A

Unstable and highly reactive due to their unpaired electron causes proteins to cross link
Produced in: radiation, cellular ageing, ischaemic reperfusion injury
Attacks: lipids, proteins, nucleic acids
Used for: cell signalling and oxidative burst

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Examples of free radicals? Worst one?

Produced in which reactions?

A

OH. (Worst), O2-, H2O2

Fenton reaction and Haber Weiss Reaction

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

Antioxidant signals? (4)

A
  • Enzymes: SOD, Catalase, Peroxidases
  • Scavengers: Vit ACE, Gluthathione
  • Storage proteins: Transferrin and Ceruloplasmin sequester iron and copper
  • Heat shock proteins: re fold proteins to maintain viability and maximise cell survival
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Light microscope changes? (3)

A

1) Cytoplasmic changes - increased water causing swelling and pale H&E followed by ribosome dispersal and pink H&E
2) Nuclear changes - Chromatin clumping
3) Abnormal Intracellular accumulations e.g fat

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

Define oncosis?

A

Spectrum of changes occur in injured cells prior to death

Cell death with swelling

16
Q

Define necrosis?

A

Morphological changes that follow cell death in living tissues

17
Q

Define apoptosis?

A

Cell death induced by regulated Intracellular program where a cell activates enzymes to degrade it’s own nuclear DNA and proteins.
Requires ATP
Cell death with shrinkage

18
Q

4 Types of necrosis?

A

2 Main: Coagulative and Liquifactive

2 Rare: Caseous and Fat

19
Q

Explain Coagulative necrosis

A

Denaturation of proteins > Release of active enzymes
Cellular architecture remains - ghost outline
Usually infarcts e.g heart
Followed by infiltration of phagocytes

20
Q

Explain Liquifactive necrosis

A

Release of active enzymes > denaturation of proteins
Neutrophils release proteases - tissue is lysed and disappears
E.g abscess, bacterial infections, brain due to fragile tissue and weak collagen matrix

21
Q

Explain caseous necrosis

A

Halfway between Coagulative and Liquifactive
Often seen with granulomas
Tissue appears as amorphous debris with no ghost outline
Found in the lung due to TB infection

22
Q

Explain fat necrosis

A

Cell death in adipose tissue
Usually pancreatitis - releases Lipases to break down TAGS and release FA’s which react with Ca 2+
Forms chalky deposits - calcium soaps
Also seen in trauma to breast tissue leaving irregular scar

23
Q

Explain gangrene

A

Grossly visible necrosis
Wet = Liquifactive e.g infection
Dry = Coagulative e.g umbilical cord after birth
Tissue is dead and can’t be salvaged

24
Q

Explain Infarction

A

Necrosis due to Ischaemia
Causes: Thrombosis, embolism, twisting of vessels, tumour causing external compression of vessel
White = occlusion of end artery, no peripheral blood vessel, area entirely without blood e.g heart, spleen, kidney
Red = 1) Organ with dual blood supply and second arterial supply is not sufficient enough to save the organ
2) Capillary anastomoses - one capillary bed occluded, other capillary beds not sufficient enough to save the organ
3) Raised venous pressure - lowered arterial filling pressure
4) Loose tissue, poor stromal support for capillaries causes further haemorrhage

25
Q

Consequences of infarct depends on… (4)

A

1) How vulnerable tissue is to hypoxia
2) Whether tissue has alternate blood supply (not end artery organ)
3) Speed of ischaemia - slower allows more time for perfusion pathways to be added
4) O2 content of blood - infarcts worse for patients with anaemia

26
Q

Define apoptosis and describe its effects on the cell

A
  • Cell death due to activation of internally controlled suicide programme
  • It is an active process using energy, the cell membrane is maintained unlike in oncosis so no release into the environment; hence no inflammation.
  • No lysosomes used
  • Cell shrinkage, eosinophilia (pink), budding of apoptotic bodies, nucleus is hydrolysed into standard lengths (shows in blotting),
27
Q

Give examples of when apoptosis occurs (3)

A
  • normal physiological processes
  • embryogenesis (digit formation and sculpting)
  • pathological processes (infected cells, immune mediated, rejection of graft by host)
28
Q

Phases of apoptosis with details

A
  1. Initiation
    INTRINSIC- starts by nuclear damage, withdrawal of growth factors/hormones or p53
    Mito becomes permeable and releases cytochrome C which activates caspases
    EXTRINSIC- external ligands (e.g TRAIL) bind to death receptors and activate caspases independent of mito
  2. Execution, caspases cleave proteins, cytoskeleton and initiate DNA degradation
  3. Degradation/phagocytosis, apoptotic bodies bud from the cell with receptors that induce phagocytosis into neighbouring cells or by phagocytes
29
Q

Name some abnormal cellular accumulations (4)

A

Lipid
Protein
Pigment (other than melanin)

  • CALCIUM, (Dystrophic- localised) in dying, ageing, atherosclorotic or damaged tissue. Leads to dysfunction e.g calcified aortic valve.
    (Metastatic - whole body) due to abnormal Ca metab by PTH, ectopic PTHrP e.g lung tumour, bone disease
30
Q

Describe LIPID accumulation

A

-LIPIDS (TAGS- steatosis), often in liver due to alcohol, DM, obesity or toxins. (Cholesterol - atheroma), often in SM making foam cells or seen in hyperlipodaemia

31
Q

Describe PROTEIN accumulation

A
  • PROTEINS (keratin - Mallory’s hyaline) makes cell eosinophilic. ⍺1-anti trypsin deficiency, (genetic) means proteases act in an uncontrolled manner e.g at lungs causing emphysema
32
Q

Describe exogenous PIGMENT accumulation

A
  • Exogenous PIGMENTS,
    (carbon/dust) phagocytosed by macrophages in lungs leading to blackened lungs (anthracosis) or peribronchial lymph nodes. (tattoo) pigment phagocytosed by macrophages in dermis that remain there
33
Q

Describe Endogenous PIGMENTS

A
  • Endogenous PIGMENTS
    Increased bilirubin is deposited in tissues causing jaundice (abnormal liver function). Lipofusin - ageing pigment is brown, not a cause of cell injury but is a sign of previous lipid peroxidation. Haemosiderin forms when there’s a localised overload of Fe2+ (bruise). Haemosiderosis - systemic overload of Fe2+ deposited in organ (caused by blood transfusion)
34
Q

Describe CALCIFICATION

A
  • CALCIUM,
    (Dystrophic- localised) in dying, ageing, atherosclorotic or damaged tissue. Leads to dysfunction e.g calcified aortic valve.
    (Metastatic - whole body) due to abnormal Ca metab by PTH, ectopic PTHrP e.g lung tumour, bone disease
35
Q

Describe the process of cellular ageing and why some cells can replicate indefinitely

A
  • accumulation of damage to DNA, misfolded proteins (amyloids) and lipofuscin
  • reduction in replicative capacity due to shortening of telomeres
  • STEM CELLS contain telomerase (and cancer cells)
36
Q

Excessive paracetamol intake

A

-Mainly phase 2; sulphonation and glucaronidation
-Small amount by phase 1 by cytochrome p450 CYP2E1 to toxic NAPQI
-NAPQI requires conjugation with glutathione.
-Depletion of glutathione leads to NAPQI poisoning and vulnerable to ROS attack.
-Liver necrosis can occurs 3-5days after paracetamol overdose. Fatal.
-People with lowered glutathione levels:
Alcoholics/ alcohol with paracetamol overdose, Malnourished, Taking enzyme-inducing drugs or with HIV/AIDS

37
Q

Excessive alcohol intake

A
  • Ethanol > acetaldehyde by alcohol dehydrogenase, cytochrome p450 enzyme (CYP2E1) and catalase
  • Acetaldehyde > acetic acid by acetaldehyde dehydrogenase

Females have reduced conc of alcohol DH so have ^ blood alcohol levels
Orientals and reduced aldehyde DH activity and so build up of acetaldehyde resulting in flushed cheeks.

CYP2E1 is inducible so increased metab of ethanol will also increase the rate of metab of other drugs using CYP2E1 enzyme so higher doses may need to be administered.

Fatty liver, alcohol toxicity results in steatosis of liver and hepatomegaly. Acute can be reversed.
Acute alcoholic hepatitis, alcohol and its metabolites are toxic and so can cause acute hepatitis and focal hepatic necrosis. Fever, jaundice, liver tenderness.

Cirrhosis, hard shrunken liver and histological micro nodules of regenerating hepatocytes surrounded by collagen bands. Irreversible and sometimes fatal.

38
Q

Excessive aspirin intake

A
  • Blocks platelets ability to make thromboxane A2 which will deplete platelet aggregation.
  • Stimulate the respiratory centre and so causes respiratory alkalosis. Metab acidosis and pH fall.
  • Aspirin also blocks CHO/lipid/protein metab increasing anaerobic metab and lactate/pyruvate/ketones production further lowering pH
  • Also cause acute erosive gastritis and GI bleeding.

Mechanisms of Disease (5 decks)

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