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Uremic Encephalopathy (UE)

Rusdidjas, Rafita Ramayati, Oke Rina dan Rosmayanti

Divisi Nefrologi Anak, Dept. Ilmu Kes. Anak FK-USU/ RSHAM

Medan

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INTRODUCTION / PENDAHULUAN

Uremia (= Urine in the blood) the final stage of progressive Renal failure the resultant multiorgan failure accumulating metabolites of proteins and amino acids and

concomitant failure of renal catabolic, metabolic, andendocrinologic processes

Uremic encephalopathy (UE) is one of many manifestationsof renal failure (RF).

Uremia: = ada urin dlm darah

Hasil akhir dari Renal failure

Merupakan resultante dari gagal MultiorganPenumpukan hasil Metab. Protein, Asam amino dan

Kegagalan klatabolik renal.

UE. Salah satu manifestasi Kegagalan ginjal

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AIMS of this paper:

Talking about:

Etiology

Patophysiology

Clinical features

Diagnosis Treatment

TUJUAN, membicarakan : Penyebab, Patofisiologi,Gejala Klinis, Diagnosis dan Pengobatan UE.

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UE

USUALLY due to

ARF (most difficult to treat / PALING SULIT DIOBATI)

CRF (Chronic Renal Failure)

ESRD (End Stage Renal Diseases= Gagal Ginjal Thp Akhir)

SEMUA RENAL FAILURE MENGSAHILKAN

-SISA-SISA METAB. PROTEIN mis UREUM, CREATININ,

URIC ACID, DLL SUBSTANS MEMBUAT KELAINANOTAK (= UE).

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Tabel 1. Beberapa substans lainnya sebagai Uremic Toxins,yang implikasinya merupakan toxisitas dari Uremic.1

---------------------------------------------------------------------------------1. Organic metabolit

Urea (cyanide)

CreatinineGuanethidine

Aliphatic aminesPhenol dan aromatic amineUric acid

Oxalic acidMyoinositol

2.3 Buthylene glycol2. Peptides dan Protein Degradasi productsMiddle moleculeAmono acidBeta1 mucroglubulines

3. EnzymesRenin

RibonucleaseLysozymes4. Hormones

Parathyroid hormoneGlucagonGrowth hormonesCalcitonineNariuretic hormones

---------------------------------------------------------------------------

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Neurological complications in renal failure

The incidence and severity of uremic encephalopathy,atherosclerosis, neuropathy and myopathy havedeclinedbut many patients fail to fully respond todialytic therapy.

Dialytic therapy or kidney transplantation induceneurological complications.

Insidens dan keparahan UE, atherosclerosis, Neuropati

dan Myopati, sudah menurun, tetapi banyak pasien yggagal dgn terapi dialysis.

Terapi dialysis dan Tranplantasi meng-induksi kom-plikasi neurologi.

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Pathophysiology of Uremic Encephalopathy..1

Complex and poorly understood 1. Accumulation of metabolites 2. Disturbance of the intermediary metabolism 3. Imbalance in excitatory and inhibitory neurotransmitters

4. Hormonal disturbance

PATOFISIOLOGI UE: komplek dan sedikit ygdiketahui.

1.Ada penumpukan hasil metabolisme 2.Ada gangguan dari intermediari metabolisme 3.Imbalans antara perangsangan dan penghambatan

neuro transmiter.4.Ada ganggaun Hormon

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Pathophysiology of uremic encephalopathy..2

.Accumulation of numerous organic substances, e.g. 5. Uremic neurotoxins ,urea, guanidino compounds, uric acid,

hippuric acid, various amino acids, polypeptides,polyamines, phenols

6. and conjugates of phenol, phenolic and indolic acids,

acetone, glucuronic acid, carnitine, myoinositol, sulphates,phosphates and middle molecules.

PENUMPUKAN Organik substans yg banyak:

5. Uremic neurotoxins, uric acid, hipurric acid, ber

bagai Amino acid, polypeptides, polyamines,phenol. dan

6. conjugate phenols, phenolic dan indolic acidacetone, glucoronic acid, carnitine, myoinositol,

sulfat, phosphate, dan molekul2 sedang.

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7. Guanidino compounds guanidinosuccinic acid, methylguanidine, guanidine andcreatinine : highly increased in serum, CSF and brain

Inhibited responses to GABA and glycine (inhibitory aminoacids)

Guanidinosuccinic acid : inhibits transketolase, a thiamine-dependent enzyme of the pentose phosphate pathway

Inhibition of transketolase : demyelinative changes to bothcentral and peripheral nervous system

Methylguanidine : seizures and uremic twitch-convulsivesyndrome

7. GUANIDINO COMPUNDS, meningkat dlm serum, penghambat GABA (Gamma Amino Butyric Acid) dan glycine

Penghambat jalur transketolase dan menghambatperobahan demyelinasi dari syaraf sentral dan perifer.Methylguanine kejang, twiching.

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8.Decrease in brain metabolic function

Increased levels of creatine phosphate, adenosine triphosphat(ATP) and glucose Decreased levels of monophosphate(AMP), adenosine diphosphate(ADP) and

lactate

9.Activation of the excitatory N-methyl-d-aspartate receptors and concomitant inhibitionof inhibitoryGABA(A)ergic neurotransmission

8. Fungsi Brain Metabolik berkurangmeningkat; creatin phosp. ; ATP; Glukosa,

Berkurang : monophosphate AMP; ADP dan Lactose

9. Aktifasi reseptor N-methyl-d-aspartat dan bersamaan dgn

inhibisi GABA [Gamma Amino Butyric Acid) (A)lergeic

neurotransmission

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10. Hormonal disturbances

parathyroid hormone, insulin, growth hormone, glucagon, thyrotropin, prolactin, luteinizinghormone and gastrin are elevated

PTH : promote the entry of calcium into neurons

Calcium : essential mediator of neurotransmitter release and plays a major role inintracellular metabolic and enzymatic processes

disrupt cerebral function by interfering with any of these processes.

10. Gangguan Hormonal.

Meningkat : PTH; Insulin; Growth Hormon; Glucagon; Thyrotoxin;

Prolactin; Luteinizing hormon; dan Gastrin.

PTH : Mendesak masuknya Ca kedalam Neuron. Ca adalah mediato

essential utk neurotransmitter.

merusak fungsi CEREBRUM oleh karena salah satuproses tersebut diatas (1-10)

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Incidence

The prevalence of UE is difficult to determine. Depends on the number of ESRD patients

In the 1990s : > 165,000 people

In the 1980s : 158,000

In the 1970s : 40,000

As the number of patients with ESRD increased,presumably so did the number of cases of UE.

Sex: Incidences are equal in men and woman.

Age: People of all ages can be affected

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Symptoms and signs

Symptoms begin insidiously. (tiba-tiba)

Progress slowly or rapidly. Changes in sensorium : loss of memory, impaired concentration, depression,

delusions, lethargy, irritability, fatigue, insomnia, psychosis, stupor, catatonia, andcoma.

Slurred speech, pruritus, muscle twitches, or restless legs.

SYMPTOM DAN SIGN

Mulai mendadak / tiba-tiba

Berlanjut Lambat atau Cepat

Timbul perubahan Sensorium, kehilangan memory, gangguan consentrasi

depressi, dilusi, letargi, irritabel, lelah, insomia, psychosis, stupor, catatonia

dan Coma. Sukar Berbicara, Pruritus, muscle twiching, atau kaki restlesness.

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Findings include the following;

Myoclonic jerks, twitches, or fasciculations (ie, uremic twitch-convulsivesyndrome postulated by Adams et al in 1997)

Dysarthria Agitation

Tetany

Seizures, usually generalized tonic-clonic

Confusion, stupor, and coma

TEMUAN YANG LAIN:

Myoclonik Jerk, Twiching, atau faciculation

( Uremic-Twiching-convulsion)

Dysarthria

Agitasi Tetany

Kejang, biasanya Tonik-Klonik

Confusi, Stupor dan Coma

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Imaging studies Brain imaging : limited value.

CT and MRI :cerebral atrophy and secondary ventricular dilatation.

ExcludingICH (Intra Cranial Hemorrhage) and

SDH (Sub Dural Hemorrhage(

Increased signal intensity in the cortical and subcortical areas of theparietal and occipital lobes

resolved after dialysis (Sembuh sesudah Dialysis)

PENCITRAAN:

Pencitraan otak, hasilnya terbatas

CT Scan dan MRI, terlihat atrophy Cerebral, dilatasi sekunder Ventricle

Exclusi : ICH ( Intra Cranial Hemorrhage) danSDH ( Sub Dural Hemorrhage)

Intensitas signal meningkat pada area Cortex dan Subcortex dari

Lobus Parietal dan Occipital.

Sembuh sesudah Dialysis

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EEG Serial EEG : useful in assessing patients and in monitoring their progress

Generalized slow wave : more severe as the condition worsens In acute uremia,

irregular low voltage with slowing of the posterior dominant alpha rhythm and occasional theta bursts.

prolonged bursts of bilateral, synchronous slow and sharp waves or spike waves

Bilateral spike discharge : myoclonic jerks

After dialysis begins, EEG may worsen for up to 6 months before slowly normalizing as renal functionimproves

EEG sangat bermanfaat utk penderita,dan utk monitor progresifitas.

Umumnya: Gelombang lambat, makin lambat makin parah

Pada akut uremia:

Ada Low voltage yang irreguler dgn gelombang lambat diposterior,rythme alfa dan kadang gelombang theta yg kacau, kalau bilateraltwiching

Sesudah dialysis dimulai, EEG masih jelek6 mgg mulai normal sesudah

Fungsi ginjal membaik

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EEG In chronic uremia,

the EEG stabilizes during long-term dialysis treatment. Deterioration corresponding to fluctuations in blood urea

levels : diffuse delta and theta activity, generalized spike-wave activity, and heightened sensitivity to photicstimulation.

PADA KRONIK UREMIA. EEG stabil selama dilysis

Kekacauan sesuai dgn kadar ureum dlm darah,

Umumnya ada aktifitas Spike waves dan sensitif ter

hadap stimulasi cahaya

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Brain histologic findings in UE

Meningeal fibrosis, glial changes, edema, vascular degeneration,

focal and diffuse neuronal degeneration, and focal

demyelination.

Small infarcts : due to hypertension or focal necrosis.

Cerebellar acute granule cell necrosis

GAMBARAN HISTOLOGI OTAK PADA UE

Meningeal fibrosis, Gial berobah, Vascular degenerasi,

fokal dan diffuse neuronal dan fokal demyelinsasi Dan infact kecil, ok. Hipertensi dan fokal necrosis

Cereberal akut granule sel necrosis.

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Neuroimage. 2007;34(2):694-701

ATROPHY OTAK, dan KELAINAN VASCULAR pd UE

Ada small necrosis, ada demyelinisasi ada fibrosis19.

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DIAGNOSIS

History

Clinical symptom and sign

EEG

IMAGING STUDIES

ANAMNESIS

GEJALA KLINIS

EEG

PENCITRAAN

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Thank you

Terima Kasih

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