Uremic encephalopathy is an organic brain disorder caused by the accumulation of toxins in the brain that are normally cleared by the kidneys. It develops in patients with renal failure when creatinine clearance falls below 15 mL/min. Symptoms range from mild symptoms like fatigue to more severe symptoms like seizures and coma. Treatment involves correcting metabolic disturbances through dialysis or renal transplantation, which typically leads to improvement, though EEG findings may not fully normalize for months. Ongoing management focuses on adequate dialysis and treatment of underlying conditions.

1. WELCOMEWELCOME
TOTO
ALLALL
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2. UremicUremic
EncephalopathyEncephalopathy
DR. MD REZUAN ULLAHDR. MD REZUAN ULLAH
Resident Phase AResident Phase A
NINSHNINSH
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IntroductioinIntroductioin
• Uremic Encephalopathy is an organic brainUremic Encephalopathy is an organic brain
disorder.disorder.
• Uremia is final stage of progressive renalUremia is final stage of progressive renal
insufficiency & resultant multiorgan failure.insufficiency & resultant multiorgan failure.
• It results from accumulating metabolites ofIt results from accumulating metabolites of
proteins & amino acidsproteins & amino acids

4. CONT…CONT…
• No single metabolite has beenNo single metabolite has been
identified as the sole cause of uremia.identified as the sole cause of uremia.
• Uremic encephalopathy (UE) is one ofUremic encephalopathy (UE) is one of
many manifestations of renal failuremany manifestations of renal failure
(RF).(RF).
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• Occurs due to build up of toxins whichOccurs due to build up of toxins which
are normally cleared by kidneys.are normally cleared by kidneys.
• It develops in pts with RF, usuallyIt develops in pts with RF, usually
when creatinine clearance levels fall &when creatinine clearance levels fall &
remain below 15 mL/min.remain below 15 mL/min.
• Manifestations vary fromManifestations vary from
•Mild symptoms (eg, lassitude,Mild symptoms (eg, lassitude,
fatigue) tofatigue) to
•Severe symptoms (eg, seizures,coma).Severe symptoms (eg, seizures,coma).
CONT..

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• Severity & progression depend on rateSeverity & progression depend on rate
of decline in renal function.of decline in renal function.
•Symptoms are usually worse in ARF.Symptoms are usually worse in ARF.
• Prompt identification of uremia as thePrompt identification of uremia as the
cause of encephalopathy is essentialcause of encephalopathy is essential
because symptoms are readilybecause symptoms are readily
reversible following initiation ofreversible following initiation of
dialysis.dialysis.
CONT…

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Patho-physiologyPatho-physiology
• It has a complex pathophysiology.It has a complex pathophysiology.
• With unknown exact cause.With unknown exact cause.
• Endogenous guanidino compounds areEndogenous guanidino compounds are
neurotoxic.neurotoxic.

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Accumulating metabolites of proteins &
amino acids affect the entire neuraxis.
Several organic substances
accumulate
• Urea,
• Guanidine compounds,
• Uric acid,
• Hippuric acid,
• Various amino acids,
• Polypeptides,
• Polyamines,
• Phenols & conjugates of
phenols,
• Phenolic and indolic
acids,
• Acetoin,
• Glucuronic acid,
• Carnitine,
• Myoinositol,
• Sulfates,
• Phosphates, and middle
molecules.

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Accumulation of diamethylarginine
• It’s a NOS ( nitric oxide synthase)It’s a NOS ( nitric oxide synthase)
inhibitor.inhibitor.
• Observed in uremic Pts leads toObserved in uremic Pts leads to
vasoconstriction.vasoconstriction.
• Induces hypertension.Induces hypertension.
• Increases ischemia & vulnerability toIncreases ischemia & vulnerability to
uremic brain.uremic brain.

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HormonesHormones
• Increased levels.Increased levels.
•PTHPTH
•InsulinInsulin
•Growth hormoneGrowth hormone
•GlucagonGlucagon
•ThyrotrophinThyrotrophin
•ProlactinProlactin
•Luteinizing hormoneLuteinizing hormone
•GastrinGastrin

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• Increased levelsIncreased levels
• Ca activityCa activity
• Organic acidsOrganic acids
• Free tryptophanFree tryptophan
• Decrease levelsDecrease levels
• GABA (gamma-GABA (gamma-
aminobutyricaminobutyric
acid)acid)
• GlutamineGlutamine
• Glycin activityGlycin activity

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• As uremia progressesAs uremia progresses
accumulation of guanidinoaccumulation of guanidino
compounds results incompounds results in
 activation of excitatory N-methyl-D-activation of excitatory N-methyl-D-
aspartate (NMDA) receptors &aspartate (NMDA) receptors &
 inhibition of inhibitory GABAinhibition of inhibitory GABA
receptors, which may causereceptors, which may cause
myoclonus & seizures..
• The encephalopathy correlates roughly
with BUN level, urea itself is not
thought to be causative.

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Abnormalities may beAbnormalities may be
associated with UEassociated with UE
• AcidosisAcidosis
• HyponatremiaHyponatremia
• HyperkalemiaHyperkalemia
• HypocalcaemiaHypocalcaemia
• HypermagnacemiaHypermagnacemia
• Over hydrationOver hydration
• Dehydration.Dehydration.

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FrequencyFrequency
• United StatesUnited States
• CrCl level < 10% of normal probablyCrCl level < 10% of normal probably
develop some degree of encephalopathy.develop some degree of encephalopathy.
• In one pediatric study, encephalopathyIn one pediatric study, encephalopathy
occurred in 40%, with a BUN level > 90occurred in 40%, with a BUN level > 90
mg/dL.mg/dL.

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Mortality/MorbidityMortality/Morbidity
• Symptoms include :-Symptoms include :-
•Somnolence & decreased mentation.Somnolence & decreased mentation.
•Asterixis usually present.Asterixis usually present.
•Symptoms are reversible followingSymptoms are reversible following
•Institution of dialysisInstitution of dialysis
•Renal transplantation .Renal transplantation .

16. •The severe complicationsThe severe complications
seizuresseizurescomacoma leads toleads to
death.death.
•Early recognition is crucial toEarly recognition is crucial to
prevent morbidity or mortality.prevent morbidity or mortality.
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CONT…

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ClinicalClinical
Symptoms begin insidiouslySymptoms begin insidiously
•Not noticed by patients but byNot noticed by patients but by
family members/caregivers.family members/caregivers.
•In many cases, CNS impairment
provides first indication of metabolic
derangements.
•Symptoms may progress slowly or
rapidly.

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• Changes inChanges in
sensoriumsensorium
include:-include:-
• Loss of memoryLoss of memory
• ImpairedImpaired
concentrationconcentration
• DepressionDepression
• DelusionsDelusions
• LethargyLethargy
• IrritabilityIrritability
• FatigueFatigue
• InsomniaInsomnia
• PsychosisPsychosis
• StuporStupor
• Catatonia &Catatonia &
• Coma.Coma.
• Patients mayPatients may
complain of:complain of:
• Slurred speechSlurred speech
• PruritusPruritus
• Muscle twitchesMuscle twitches
• Restless legs.Restless legs.

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HistoryHistory
• Early symptoms
1. Anorexia
2. Nausea
3. Restlessness
4. Drowsiness
5. Diminished ability to
concentrate
6. Slowed cognitive
functions
• More severe symptoms
1. Vomiting
2. Emotional volatility
3. Decreased cognitive
function
4. Disorientation
5. Confusion
6. Bizarre behavior

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• As uremic encephalopathy progresses,
patients may develop:-
• Myoclonus
• Asterixis
• Seizures
• Stupor &
• Coma.

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Physical examPhysical exam
• Variable & depending on severity ofVariable & depending on severity of
encephalopathy.encephalopathy.
• Neurologic findings range fromNeurologic findings range from
normal to a comatose state.normal to a comatose state.
• Altered mental status (confusion)
• Cranial nerve signs (nystagmus)
• Papilledema
• Hyperreflexia, clonus, asterixis
• Stupor
• Coma occurs only if uremia
remains untreated & progresses.

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CONT…..
•Myoclonic jerks, twitches, orMyoclonic jerks, twitches, or
fasciculationsfasciculations
•AsterixisAsterixis
•DysarthriaDysarthria
•AgitationAgitation
•TetanyTetany
•Seizures, usually generalized tonic-Seizures, usually generalized tonic-
clonicclonic

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Differential DiagnosisDifferential Diagnosis
1. Hepatic
Encephalopathy
2. Hypertensive
Encephalopathy,
3. Hypoglycemia
4. Hyponatremia
5. Hypernatremia
6. Subdural Hematoma
7. Hyperosmolar Coma
8.8. Alzheimer DiseaseAlzheimer Disease
9. Status Epilepticus
10.Intracranial
haemorrhage

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Laboratory StudiesLaboratory Studies
11.. Electrolytes, BUN, creatinine, & glucoseElectrolytes, BUN, creatinine, & glucose
A-A- Markedly elevated BUN & creatinineMarkedly elevated BUN & creatinine
levels indicate UE.levels indicate UE.
B-B- Obtain serum electrolyte & glucoseObtain serum electrolyte & glucose
measurements to rule out other causes:-measurements to rule out other causes:-
-hyponatremia, -hypernatremia,-hyponatremia, -hypernatremia,
- hyperglycemia &- hyperglycemia &
-hyperosmolar syndromes-hyperosmolar syndromes

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2.2. Obtain CBC to detect leukocytosis,Obtain CBC to detect leukocytosis,
which may suggest an infectiouswhich may suggest an infectious
cause and determine whether anemiacause and determine whether anemia
is present.is present. (Anemia may contribute to the
severity of mental alterations.)
33.. Serum calcium, phosphate and PTHSerum calcium, phosphate and PTH
levels to determine the presence oflevels to determine the presence of
hypercalcaemia, hypophosphatemia,hypercalcaemia, hypophosphatemia,
and severe hyperparathyroidism,and severe hyperparathyroidism,
which cause metabolicwhich cause metabolic
encephalopathy.encephalopathy.

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Imaging StudiesImaging Studies
• Brain imaging is of limited valueBrain imaging is of limited value
•MRI or head CT with severe
neurologic symptoms to rule out
structural abnormalities (eg, CVA,
Intracranial mass).
•CT does not demonstrate any
characteristic findings for UE.

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Other TestsOther Tests
• Electroencephalogram:Electroencephalogram:
An EEG is commonly performed onAn EEG is commonly performed on
patients with metabolic encephalopathy.patients with metabolic encephalopathy.
Findings typically include the following:Findings typically include the following:
(1) slowing and loss of alpha(1) slowing and loss of alpha
frequency wavesfrequency waves
(2) disorganization(2) disorganization
(3) intermittent bursts of theta and(3) intermittent bursts of theta and
delta waves with slow backgrounddelta waves with slow background
activity.activity.

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Cognitive function testsCognitive function tests
Several cognitive function tests are used to evaluateSeveral cognitive function tests are used to evaluate
UE.UE.
• Uremia may result in worse performance onUremia may result in worse performance on
•The trail-making test:- which measures
psychomotor speed.
•The continuous memory test:- which
measures short-term recognition.
•The choice reaction time test:- which measures
simple decision making.
•Alterations in choice reaction time appear
to correlate best with renal failure.

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Histologic FindingsHistologic Findings
Brain histologic findings include:-
• Meningeal fibrosis
• Glial changes
• Edema
• Vascular degeneration
• Focal & diffuse neuronal degeneration
• Focal demyelination
• Small infarcts are also seen & are probably
due to HTN or focal necrosis

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ProceduresProcedures
Lumbar puncture:
•Not routinely performed, however
•It is indicated to find other causes if
a patient's mental status does not
improve after initiation of dialysis.
•No specific CSF finding indicates UE.

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TreatmentTreatment

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Medical CareMedical Care
• No medications are specific.No medications are specific.
• Care includes correcting metabolicCare includes correcting metabolic
disturbancedisturbance
•In ARF or CRF indication for early
initiation of :-
•Hemodialysis
•Peritoneal dialysis
•Continuous renal replacement
therapy.

33.  After beginning dialysis, patient
generally improves clinically.
 EEG findings may not improve
immediately.
•In ESRD, EEG improve after
several months but may not
completely normalize.
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CONT…

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Address the following factors:
1. Adequacy of dialysis
2. Correction of anemia
3. Regulation of calcium & phosphate
metabolism.
4. Medical parathyroidectomy.
5. Infections need to be treated
appropriately.

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SeizuresSeizures
May be treated with anticonvulsants.
• These drugs should be administered at
lower-than-usual doses.
• Low albumin levels can lead to higher
levels of unbound anticonvulsant.
• The unbound drug is therapeutically active
fraction.

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ConsultationsConsultations
1. Nephrologist
2. Vascular surgeon for placement of vascular access in
patients with ESRD.
3. Neurologist if symptoms do not improve upon
initiation of dialysis therapy.
4. Dietitian the one familiar with renal diseases.
5. Specialist in critical care medicine
6. Neurosurgeon Neurosurgical intervention for
intracranial hemorrhage or subdural hematoma.
7. Infectious disease specialist: Bacterial meningitis
remains a high cause of mortality in hemodialyzed
patients, often because of delay in treatment.

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Diet:Diet:
•To mainitain adequate nutrition
•Low-salt
Activity:Activity:
•Instruct patients with significant
symptoms to continue bed rest.

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Follow-upFollow-up

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•Patients need close follow-up in acute
stage of uremic encephalopathy.
•After underlying problem is treated
properly, the symptoms should
resolve.
•Levels of anticonvulsant drugs must
be closely monitored to prevent
toxicity.

40. CONT…CONT…
Further Outpatient Care:
•Schedule maintenance HD for ESRD.
•Carefully monitor mental status.
•Administer medications (eg, iron,
erythropoietin, phosphate binders,
vitamin D analogues) for patients
with ESRD to optimize their quality
of life.
•Avoid sedatives.
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Complications
If untreated:
• Seizures
• Coma
• Death

42. PrognosisPrognosis
•The prognosis is generally favorable if
treatment is successful.
•With prompt dialytic therapy, the
mortality rate is low.
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43. Patient EducationPatient Education
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To ensure that treatment is initiated
early, instruct patients & their family
members & caregivers about the need
for prompt medical evaluation when
mental status changes occur.

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Thank YouThank You