Cell Injury and Death

Question 1

Explain the tissue response to injury, using cardiac Myocytes and hypertension as an example.

Answer 1

due to increased workload on heart,

• hypertrophy (myocyte increasing in size)
• cardiomegaly.
• if workload not reduced or several factors contribute (atherosclerosis) = myocardial infarction.

Question 2

Describe a few examples for the aetiology of cell injury.

Answer 2

• hypoxia.
• toxins (drugs, poison, alcohol)
• physical agents ( trauma, temperature extremes, pressure changes, electric currents).
• radiation.
• micro-organisms.
• nutrition/ dietary deficiencies.
• genetic + aging.

Question 3

List a few reasons for Hypoxia/ oxygen deprivation.

Answer 3

• Hypoxaemic hypoxia : arterial content of O2 low.
• Anaemic hypoxia : decreased O2 transport by HB.
• ischaemic hypoxia : interruption in flow/ stagnant.
• Histiotoxic hypoxia : inability to utilise the O2, disabled oxidative phosphorylation.

Question 4

How does the immune system damage bodies own cells?

Answer 4

• hypersensitivity secondary to overly vigorous immune response.
• autoimmune reaction where cannot distinguish from non self.

Question 5

name some cell components most susceptible to injury.

Answer 5

• cell membrane.
• nucleus.
• proteins (structural, enzymes)
• mitochondria.

Question 6

name a few consequences of hypoxia.

*use mitochondria as guiding victim.

Answer 6

• ATP production affected.
• NA/K pump affected which leads to cell swelling oncosis, influx of Ca2+.
• Glycolysis affected so lactate buildup, lowering pH which causes chromatin to clump.
• ribosomes detach from RER so decreased protein synthesis and increase in lipid deposition.

Question 7

describe the appearance of dying cells under a light microscope.

Answer 7

water accumuluated,
Pyknosis- nucleus shinking,
Karyorrhexis- fragmented,
Karyolysis - nucleus gone.

Question 8

compare the appearance of irreversibly vs reversibly dying cells under an electron microscope.

Answer 8

• blebs appear in reversible injury (might shed)
• nuclear pyknosis, karyolysis or karyorrhexis in irreversible and clumping of chromatin in reversible.
• mitochondrial swelling in both.

Question 9

Define Oncosis.

Answer 9

cell death with swelling, spectrum of changes that occur in injured cells prior to death.

Question 10

Define Necrosis.

Answer 10

Morphological changes that occur after a cell has been dead for some time (12-24h after).

Question 11

Define Apoptosis.

Answer 11

Programmed cell death.

Question 12

what are the 2 types of necrosis.

Answer 12

• Coagulative : protein denaturation (ischaemia of solid organs)
• Liquefactive : enzyme release ( ischaemia in loose tissue, presence of neutrophils)

Question 13

what does coagulative necrosis look like?

Answer 13

denaturation of proteins dominates, cellular architecture somewhat preserved, “ghost outlines”

Question 14

what does liquefactive necrosis look like?

Answer 14

enzyme degradation greater than protein denaturation.

leads to enzymatic digestion (liquefaction) of tissues by neutrophils releasing enzymes.

Question 15

what is caseous necrosis?

Answer 15

contains amorphous (structureless) debris, particularly associates with infection like TB.
*cheese like, no cell outline.

Question 16

what is fat necrosis?

Answer 16

lipase acting on cells.

Question 17

compare physiological apoptosis and pathological apoptosis.

Answer 17

Physiological - to maintain homeostasis, hormone controlled involution, embryogenesis to define certain features, like gaps between fingers.
Pathological - cytotoxic T-cells killing virus infected, neoplastic cells, DNA damaged cells.

Question 18

describe the intrinsic pathway of apoptosis.

Answer 18

• initiation from within cell, triggered by DNA damage, growth factor withdrawal or hormones.
• p53 protein activated and outer mitochondrial membrane leaky.
• Cytochrome C released and activated caspases to dismantle cellular structures.

Question 19

describe the extrinsic pathway of apoptosis.

Answer 19

• initiated by extracellular signals like cells in danger. eg: tumour cells, virus infected cells.
• TNFa by T-killer cells that bind to cell membranes death receptor and activates caspases.

Question 20

Describe degradation and phagocytosis following intrinsic/ extrinsic pathways.

Answer 20

• cells shrink and break up into apoptotic bodies, they have proteins on surface to be recognised by phagocytes.
• degradation within phagocyte/ neighbour.

Question 21

compare and contrast apoptosis vs Necrosis.

Answer 21

• shrinking of cell vs swelling.
• budding vs blebbing with cell membrane disrupted.
• phagocytes with no inflammation vs release of proteolytic enzymes with inflammation.

Question 22

Define gangrene.

Answer 22

necrosis visible to naked eye.
dry - coagulative, due to exposure to air.
wet - liquefactive, due to infection.
gas - anaerobic bacteria, after motor accidents.

Question 23

Define Infarction.

Answer 23

necrosis caused by reduction in arterial blood flow, can lead to gangrene.

Question 24

Define infarct.

Answer 24

an area of necrotic tissue which is the result os loss of arterial blood supply.

Question 25

Name a few reasons for infarction and a few places where its common.

Answer 25

reasons - atherosclerosis, thrombus, twisting, compression.

places - heart, brain, lungs, kidney, limbs, GI and Testicles.

Question 26

Distinguish between red and white infarcts.

Answer 26

• Red : liquefactive, in loose tissue, haemmorhagic, usually has dual blood supply so when one area necrotic other blood supply directed so area red in appearance. eg - lung, bowel or brain.
• white : coagulative, in solid organs like heart, spleen or kidney, end of an artery, wedge shaped.

Question 27

What is ischaemia-repurfusion injury?

Answer 27

if blood flow returned to damaged area it could be a lot more damaging.

• increased production of oxygen free radicals.
• increased neutrophils so more inflammation and increased tissue injury.
• complement pathway.