Q.475. What is the role of proinlflammatory cytokines in the pathophysiology of sepsis?
INTENSIVE CARE NEPHROLOGY
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| Single kidney |
Q.475. What is the role of proinlflammatory cytokines in the pathophysiology of sepsis?
A. Proinlflammatory cytokines: 👉 [TNFa– IL1B-IL6-IL8] released in response to
infectious stimuli: TNFa– IL1B wide
range effects incl.: {activation
of macrophage , lymphocytes, reticulocytes, incr. expression of
adhesion molec-ules & incr. production of inflammatory cytokines.}
Q.476.What
is the role of antiinlflammatory cytokines in the
pathophys-iology of sepsis?
A. Antiinflammatory cytokines 👉[TNF B- IL10-IL13]
they
Reduce the pro-inflamm. cytokines (TNFa – IL1B),
furthermore, in animal models, these cytokines ð a KEY component of Sepsis, As: infusion of TNFa– IL1B Shock state, and A.B.
to these cytokines attenuate the shock-like
state.
Q.477.What
is the role of Neutrophil in the pathophysiology of sepsis?
A. Neutrophils: in critically ill ptn. Abn. Neutrophil
function Reduced migration & superoxide production
& bacterial
killing = ALL impair host def-ence
mechanisms.
Q.478.What
is the role of other mediators?
A. Other mediators:
1)
PGE2: Responsible of V.D. of septic shock.
2)
Thromboxane A2: V.C.
& Platelet & leukocyte aggregation.
œœ
3)
PAF: produced by many cells in resp. to inflmm.
stimuli & stimulate leukocyte adhesion to endothelium.
4)
NF.KB :
(a
transcription f. located in cytoplasm of mast cells) Recently:
stimulation of cells by cytokines, bacteria or viral by-products Translocation
of NF. KB fr. cytoplasm to
nucleus, where it regulates transcription of target genes, wch. activate &
modulate cytokines, chemokines & receptors of [Sepsis-SIRS-ARDS -MODS.].
Q.479. How
can the coagulation system affected by sepsis?
A. Sepsis:
Protein C &
downregulate its convertion to active protein C Thrombosis.
Dramatic of anti-thrombin III.(which inhibit thrombin III
& f.X.) microthrombosis MODS.
Q.480. What
are Toll-like receptors? What
is its significance?
A. Toll-like receptors: [T.L.Rs.] (toll=mark):[Proteins tht recognize sp. patt-ern of a pathogen].
Ten human T.L.Rs, when
stimulated Cascade
of Signal-ing events production
of cytokines & effector molecules, incl. (TNFa– IL1-IL6.) wch’re the Iry transduction of the inflamm. resp. to the
invading organism.
Q.481.What is the role of the kidney in T.L.R.s. expression?
A. T.L.Rs. are necessary for HOST DEFENCE , The kidney express most of the T.L.Rs., but T.L.R. 2 & 4 most studied,
because they have a potential role in mediating G+ve (Tol 2)
& G -ve
(Tol. 4) signaling.
- A possible role of Local T.L.Rs. in mediating R.F. is evaluated,
moreover, Local T.L.Rs. directly
mediate AKI seen in sepsis.
Q.482. Describe
the clinical features of sepsis?
A. C.F. > [fever-hypothermia- tachycardia-tachpnea-leukocytosis-leukopenia].
Many cytokines > Sn
& Sm. e.g. TNFa & IL1 Fever, .. Failure to
dev. fever M.R.,
hyperglycemia,
hypoglycemia, hypocalcaemia, hyponatremia, hypokalemia, hypomagnesemia &
hypophosphatemia all
are seen.
- Sev. sepsis Hypotension due to N.O. release & dcr.
circulatory volume.
- Intravascular
vol. depletion occ. due to:
1) Incr.
insensible losses.
2) Incr.
microvascular
permeability.
3) Dcr.
systemic vascular
resistance. (SVR).
- Once resuscitation occur Hyperdynamic CVS é C.O. & SVR.
Q.483.What is the effect of sepsis on the heart & respiratory system?
A. Sepsis Myocardial
depression LVED volume & LVES
volume, the accused f. TNFa– IL1,
……. also, N.O. -ve intrope.
- Hypoxia & tachypnea,
ARDS= 40
%. Adrenal insufficiency= 40 %.
- DIC, Lab thrombocytopenia, PT, a.PTT, D-dimer.
Q.484.What
is the effect of sepsis on the CNS & peripheral nerves?
A. Septic
encephalopathy= the most
common in ICU, due to
1)
Impaired mitochondrial
function.
2)
Impaired O2
extraction by the brain.
3) Disruption of astrocyte
end-feat.
4) All inflmm.
mediators Neural inj., confusion, lethargy,
obtundation & coma.
5)
Critical illness polyneuropathy due
to axonal
degeneration, ch.ch. by hyporeflexia, weakness, distal
more than proximal.
Q.485. Explain,
how could the kidney be affected in sepsis?
A. Incidence: 9-60%. M.R.: 50%
- Clinically: ATN up to [Bilateral
Cortical Necrosis].
- Hypotension Renal hypoperfusion AKI. As does nephrotoxic ag.s.
Role of
Cytokines:
1. TNFa Release fr. (mesangial)
cells:
i.
Leukocytes accumulation in
the glomeruli.
ii.
Apoptotic glomerular endothelial
cell death.
iii. Endothelin production.
2.
IL1:
i. V.C.
ii. Neutrophil
aggregation.
iii. More cytokine release.
3.
Thromboxan E2 [RBF, GFR, Afferent V.C.]. œœ
4.
Leukotriens released é endotoximia RBF & GFR.
5.
PAF (platelet aggreg. factor) Both aff. & eff. arteriolar resistance & GFR.
6.
Endothelin 1
incr. é response to septic mediators incl. TNFa
Renal V.C., inhibition of Na+ & water reabsorption by collecting tubules.
Q.486.What
are the potential contributors of MODS in sepsis?
A. Potential contributors
of MODS:
Hypoperfusion.
‚ Microvascular thrombosis.
ƒ Mitochondrial dysfunction.
„ Ischemia /Reperfusion injury.
… Circulating inflammatory load.
† Diffuse endothelial cell injury.
‡ Increased tissue N.O.
ˆ Bacterial toxin translocation.
Q.487.What
are the main tools in management of sepsis?
A. Three main items:
I. Eradication of infection. II. Hemodynamic support. III. Activated vitamin
C.
Q.488.What are
the recommendations in infection eradication?
A. A.B.
coverage should
be Double é
:
1) Pseudomonas aerogenosa.
2) Febrile Neutropenia.
3) Intra-abdominal infection.
Q.489. How
can you perform hemodynamic support in sepsis?
A. At least 10 L./crystalloid/1st 24h., as profound
hypotension occ.
due to: [Volume depletion-
Peripheral V.D.-
Incr. permeability].
So, aggressive vol. resusc-itation, boluses
of fluid given until reperfusion occur, e.g.
urine output.
- Colloid Vs crystalloids No
evidence of preference.
Q.490.What is the goal-directed
therapy in hemodynamic support?
A. Goal-directed therapy a use of the foll. end-points to
improve M.R.:
C.V.P.
‚ Hematocrit.
ƒ Mean arter. B.P.
„ C.V. O2 saturation.
- Tools:👉
1) Dopamine & Nor. 1st choice
in sepsis:Dopamine: limited use, as sepsis incr. its chrono. effect tachycardia &
arrhythmia. - Nor.: as effective as dopa.
in B.P, but less cardiac effect,
it doesn’t C.O. as dopa.
2) Epinphrine:
used in refractory
hypotension, but s. lactate.
3) Vasopressin: of posterior pituitary V.C. & antidiuresis.
It’s incr. (20-200) times in shock, it cn spare Nor., B.P. & cardiac index.
-Alth. [Nor.] Profound
glom. affer. V.C., [Vasopressin] G. effer.V.C. GFR, but Vasopressin coronary V.C. AMI. & hs No +ve inotropic effect.
4) Doputamine: cn
be used to O2, but cn potentiate hpt.,
due to B2 V.D., it is recommended for low cardiac index (<
2.5 L/min/m2) after vol. resuscitation, but if B.P. 80 , it shd be used with Nor.,
to mediate peripheral V.C.
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