Ischaemia reperfusion injury and morphology of reversible injury

1. Cell Injury (contd.)
Dr. Saket Kumar

2. Ischaemia – Reperfusion injury
• Long duration of ischaemia
• Cell death occurs due to restoration of blood supply (reperfusion)
• Common in myocardial and neural cells
• 3 aspects:
- Calcium overload
- Excessive generation of free radicals
- Subsequent inflammatory reaction

3. • Calcium overload
- Increased calcium supply to ischaemic cell due to restoration of blood
supply
- Calcium pumps are not functioning due to decreased ATP
- Increase in intracellular Ca2+ Lipid peroxidation & further
membrane damage.

4. • Excessive generation of free radicals
- Oxidative phosphorylation – ATP is formed from oxygen and hydrogen
- In this reaction 3 free radicals are formed which are degenerated
simultaneously, hence no harm is caused.
- If free radicals are not degenerated they cause further injury to ischaemic
cell
- 3 radicals:
O’
2
H2O2
OH-

6. Cytotoxicity of free radicals
- Oxidative stress
Lipid peroxidation
DNA damage
Cytoskeleton damage

7. • Subsequent inflammatory reaction
- Large amount of neutrophils come with reperfusion
- They utilise large amount of oxygen and produce free radicals

8. Stress proteins – Heat shock proteins(HSP)
• family of proteins that are produced by cells in response to exposure
to stressful conditions
• perform chaperone functions
• ubiquitin, which marks proteins for degradation, also has features of
a heat shock protein.

9. Morphology – Reversible Injury
• Morphologic forms:
- Hydropic change
- Hyaline change
- Mucoid change
- Fatty change

10. • Hydropic change
- Commonest and earliest form of cell injury
- Synonyms – Cloudy swelling
Vacuolar degeneration
- Pathogenesis – Impaired regulation of sodium and potassium
Increased conc. of sodium in cytoplasm
Accumulation of water

11. - Morphology – Organs like kidney, liver, pancreas, heart muscle are commonly
affected.
Gross – Enlarged
Cut surface bulges out and slightly opaque
Microscopic – Hydropic swelling kidney:
Tubular epithelial cells are swollen
Cytoplasm contain vacuoles – vacuolar degeneration
Cytoplasmic blebs
Nucleus pale
Interstitium microvasculature compressed

13. • Hyaline change
- Hyalinisation – glassy, homogenous and eosinophilic appearance of
proteinaceous material in H&E stained sections
- Intracellular and Extracellular.

14. - Intracellular hyaline – epithelial cells
Hyaline droplets – proximal tubular cells, due to
excessive reabsorption of plasma protein in
proteinuria
Mallory’s hyaline – aggregates of intermediate
filaments in alcoholic liver cell injury
Nuclear and cytoplasmic hyaline inclusions –
viral infections
Russell’s bodies – excessive Ig in RER of plasma cells

16. - Extracellular hyaline – connective tissue
Hyaline degeneration in leiomyomas of uterus
Hyaline arteriosclerosis of renal vessels in HTN
and diabetes mellitus
Corpora amylacea – concentric hyaline laminae
in prostate, brain and spinal cord in old age

18. • Mucoid change – mucus – secretory product of mucous glands
(epithelial mucin) as well as some
connective tissues (myxoid change)
protein + mucopolysaccharides
mucin is chief component

19. - Epithelial mucin – Inflammation of mucous glands
Obstruction of duct – mucocele of oral cavity
Mucin producing tumours (ovary, stomach, large bowel)

21. - Connective tissue mucin – Myxoid change in some tumours. Ex –
neurofibroma, fibroadenoma, soft tissue sarcoma

22. • Fatty change (steatosis) – intracellular accumulation of neutral fat in
cytoplasm of parenchymal cells.
- Liver – commonest site of accumulation – fatty liver
Etiology a) Conditions with excess fat:
Obesity
Diabetes Mellitus
Congenital hyperlipidemia
b) Liver cell damage:
Alcoholic liver cell injury
Hypoxia
Protein calorie malnutrition
Hepatotoxin (Carbon tetrachloride, chloroform, ether)
Drug induced (methotrexate, steroids, etc.)

23. Pathogenesis of fatty liver
1) Increased entry of free fatty acids into liver
2) Increased synthesis of free fatty acids by
liver
3) Decreased conversion of free fatty acids
into ketone bodies
4) Increased alpha glycerol phosphate
5) Decreased lipid acceptor protein
6) Block in excretion of lipoprotein

24. - Morphology: Gross
Liver is enlarged
Tense glistening capsule with rounded margins
C/s – pale yellow, greasy to touch
Microscopy
multiple lipid vacuoles in cytoplasm
Microvesicular
Macovesicular
Fatty cyst
Lipogranuloma

25. Thank You