ANOKSIA

Cedera yang paling sering, dan paling

mematikan adalah ANOKSIA, yaitu tidak adanya
oksigen dalam sel.
Penyebab terbanyak kematian pada manusia
(paling sering merusak otak dan jantung).
Hipoksia, suatu keadaan berkurangnya suplai
oksigen, juga dapat mematikan apabila cukup
berat (seringkali disebabkan karena
berkurangnya aliran darah = ISKEMIA).
NORMALNYA
1. dlm mitokondria, as lemak  oksidasi  energi
2. energi untuk membuat ATP dari ADP (fosforilasi)
 energi disimpan dlm molekul ATP
3. ATP dikirim oleh mitokondria ke organel2
(mitochondrial dance)  sbg bahan bakar  energi
yg diperlukan dlm proses kehidupan (gerak, sekresi,
fungsi memompa)
4. energi yg disimpan dlm ATP dilepas diberbagai tempat
dgn merubah menjadi ADP + fosfate
PERAN OKSIGEN  ENERGI  KEHIDUPAN SEL

OKSIGEN KURANG/ HILANG  KEHIDUPAN SEL ???

ISKEMIA FOSFORILASI ATP SINTESIS <<
OKSIDATIF(-)

POMPA & GLIKOLISIS ANAEROBIK

LEKAT ENZIM (energi + ATP sementara)
KE MEMBR <<

Na,Kalsium, AS.LAKTAT>> GLIKOGEN <<

Air tertimbun
RE
DNA SINTESIS POLIRIBOSOM VER
SEL BENGKAK GUMPAL RNA (-) JADI RIBOSOM SI
(terakhir mito BEL
kondria)
energi SINTESIS RIBOSOM LEPAS
habis PROT (-) DARI rER

membran keasaman membran IRE

rusak intrasel >> lisosom rusak VER
SI
BEL
isi keluar sel dihancurkan isi/enzim keluar
struktur myelinoid (+)
Toleransi terhadap hipoksia :

- Otak : 3 menit
- Ginjal & hepar : 15-20 menit
- Miokardium : 20-30 menit
- Otot skelet : 60-90 menit
- Otot polos vaskuler : 24-72 jam
- Kuku & rambut : beberapa hari
 A Multiple Front Attack…

All attacks potentially lethal..

1. Anoxia stops ATP synthesis.
2. The cells can no longer derive energy from oxydative
processes, they switch to the anaerobic splitting of their
glycogen stores (anaerobic glycolysis), enable to
produce some energy (and ATP) without oxygen for a
while, until their glycogen stores are depleted (for
maximally 20 to 30 minutes in the case of myocardial
cells or hepatocytes, the glycogen richest cells).
3. As results, lactic acid (the end product of glycolysis
splitting) increased amount within the cells while
glycogen granules disappear
1. Increased concentration of lactic acid causes a tight
coiling and clumping of DNA in the nucleus (nuclear
pycnosis), which stops new RNA synthesis
(therefore protein).
2. The cation and water pump stop pumping out the
sodium, calsium and water because it need energy.
Progressive accumulation of sodium and water in the
cell, make the cell swells. The last saccular organelle to
swell is the mitochondria.
3. Since no more mRNA is available, polyribosome
complexes disperse into single ribosome because the
string that hold their individual ribosome together (the
mRNA thread), and then protein synthesis ceases
because no more mRNA arrives to be translated into
amino acid chains.
The change caused by anoxia are reversible, if oxygen
return to the cell, it will recover.
Oxydation and phosphorylation, ATP generation will be
resumed in the mitochondria that are still intact.
The cation pump will start operating again.
Accumulated lactic acid will be oxydized away, the cell’s
DNA will uncoil again, allowing RNA synthesis again
Irreversible damage DNA will be wrapped up
New mitochondria replace the damaged mitokondria
 If no oxygen is made available again, the cell will be
doomed to death:
1. Numerous fractures and break up develop on plasma
membrane and unit membrans. Various intracellular
components leak out into the extracellular space and
blood.
2. Increased of free phosphate within the dead cells
because membran phospholipid molecules, DNA, RNA
disintegrated.Disintegration of cell membrane releases
their phospholipid and cholesterol building block
reassembled together with cholesterol into myelenoid
structure.
3. Lysosome seem to be the last saccular organelles that
rupture, release the specific enzymes into the
cytoplasmic matrix. Cathepsin D is the lysosome
enzyme that appear shortly before the onset of
irreversible anoxic injury.
It has been suggested that anoxia destroys cells
because the lactic acid induced intracelular acidity
ruptured the lysosomal membranes and releases their
enzymes, and than digests their own cell (Cathepsin
D, acid phosphatase etc).
4. Numerous fractures and break up develop on plasma
membrane and unit membrans. Various intracellular
components leak out into the extracellular space and
blood.
1. Increased of free phosphate within the dead cells
because membran phospholipid molecules, DNA, RNA
disintegrated.
2. Lysosome to the last saccular organelles that rupture,
release the specific enzymes into the cytoplasmic
matrix. Cathepsin D is the lysosome enzyme that
appear shortly before the onset of irreversible anoxic
injury.
Massive extracelular calsium enter the cytoplasm, bind
to free phosphate and fatty acids, producing
intracelular precipitates of calsium phosphate and
calsium fatty acid. Finally, lipid accumulate in some
types of necrotic cells (heart), they enter from the
bloodstream.
Anoxic necrosis in most organ (heart, liver, kidney,
spleen)  solid necrotic material (coagulation
necrosis), while in the brain  liquid necrotic material
(liquefaction necr) breakdown of myelin are water
soluble while fibroblast and collagen are rudimentary
in the brain.
HE stains (24-48 hours):
irreversible necrosis of cell appears as homogenous red
mass (eosinophilic/acidophilic) without nucleus, because
of all of its cytoplasmic and nuclear acid acid (normally
stained blue) have disappeared, and only protein leaving
behind (stained red)