Objectives for NS 2:

• Cytotoxic, osmotic and vasogenic brain edema)• Thiamine-responsive polioencephalomalacia of

ruminants

• Thiamine deficiency in carnivores

• Lead poisoning

• Salt poisoning

• Toxin-induced vasogenic brain edema

You should be able to define, describe pathogenesis,

list lesions and know how to diagnose the following

conditions:

Increased intracranial pressure

Brain swelling (cerebral edema)

E. Simko WCVM

Response to injury - Brain edema

Brain swelling (edema)

Intracranial pressure

Blood perfusion pressure

Ischemicnecrosis

E. Simko WCVM

Response to injury - Brain edema

Brain edema

• Cytotoxic (intracellular)

• Extra cellular edemaOsmotic Vasogenic

E. Simko WCVM

Response to injury - Brain edema

• Gross: cerebellar coning (herniation)cerebral herniationflattened gyri

• Microscopicallyneuronal necrosisedema is not evident in most cases

Diagnosis:

E. Simko WCVM

Response to injury - Brain edema

Polioencephalomalacia (PEM)

• Thiamine-responsive PEM of ruminants• Lead poisoning in ruminants• Salt poisoning in pigs & occ. in rumin.• Hypoxia

Cytotoxic edema (cellular degeneration)

Thiamine-responsive polioencephalomalaciain ruminants

• Disturbance of thiamine production/absorption

concentrate ruminal pH change in flora

Bacterial thiaminase

• [sulfur, sulfates, sulfides] in diet or water

Etiology

E. Simko WCVM

Response to injury - Brain edema

PathogenesisCytotoxic edema - Thiamine deficiency

• Thiamine interferes with glucose

metabolism and Krebs cycle in CNS• ATP production• Na/K transport is impaired

• Intacellular H2O (hydropic degeneration)

• Cellular swelling (Cytototoxic edema)• Energy exhaustion• Intacranial pressure & blood perfusion• Ischemic necrosis

E. Simko WCVM

Lesions

• Brain swelling (flattened gyri, cerebellar coning)

• Yellow cortical discoloration(autofluorescence under UV light)

• Cortical liquefaction and cavitation

HistologyLaminar cortical

necrosisE. Simko WCVM

Cytotoxic edema - Thiamine deficiency

Diagnosis

• History

• Response to thiamine

• Gross and histologic lesions

• Rule out the other causes of PEM

E. Simko WCVM

Cytotoxic edema - Thiamine deficiency

Dietary thiamine deficiency in carnivores

• Dog, cat, mink (Human – Wernicke’s encephalopathy)

• Depend on exogenous source of vitamin

• Pathogenesis: diet with thiaminase, sulfur

preservatives or exposed to high temperature

Lesions:Symmetrical necrosis of thalamic andmid-brain nuclei

E. Simko WCVM

Cytotoxic edema - Thiamine deficiency

Lead poisoning

Cattle

Waterfowl

Source:

Old batteries and paint

Lead shotgun pellets

Lesions:

Polioencephalomalaciasimilar to thiamine resp.

PNS degeneration(Esophageal/crop dilation

and impaction)

E. Simko WCVM

Brain edema

Pathogenesis in cattle

• Direct endothelial injury vasogenic edema

• Damaged metabolism cellular swelling

• Energy exhaustion

• Increased intracranial pressure

• Failure of blood perfusion

• Ischemic necrosis

Brain edema - Lead poisoning

E. Simko WCVM

Diagnosis

• Gross and histologic lesions

• Lead particles in the rumen

• Lead level in liver and kidney

E. Simko WCVM

Brain edema - Lead poisoning

Osmosis and semi-permeable cellular membrane

Hypo Os

Hyper Os

Hypo Os

Hyper Os

Swelling

Shrinkage

Osmotic brain edema

H2O

E. Simko WCVM

Water intoxication ( IV H2O, behavioral, ADH)

N

Ed

ema

Deh

ydr.

Brain edema

BRAIN PLASMA BRAIN PLASMA

H2O

N

Ed

ema

Deh

ydr.

Water deprivation +/- high salt

Dehydration

t = 0 hr

HyperNa

Osmotic brain edema - Salt toxicity

BRAIN

N

Ed

ema

Deh

ydr.

BRAIN PLASMA

NaCl

N

Ed

ema

Deh

ydr.

PLASMA

Na+Cl-Na+

Na+

Cl-

Na+

Na+

Cl-

Cl-

Cl-

Na+

Na+

Cl- Na+

Cl-

Na+

Cl-

H2O

Cl-

Cl-Na+

Na+

Dehydration

NormoNaNormoOs HyperOs

Equilibration of CNS hyperNa

PLASMAHyperNa

t = > 36 hr

HyperNa

Osmotic brain edema - Salt toxicity

N

Ed

ema

Deh

ydr.

BRAIN

Cl-

Na+ Na+Cl-Na+

Na+

Cl-

Na+

Na+

Cl-

Cl-

Cl-

Na+

Cl-

Dehydration Dehydration

PLASMANormoNa HyperNa

N

Ed

ema

Deh

ydr.

BRAIN

AA

AA Na+Cl-Na+

Na+

Cl-

Na+

Na+

Cl-

Cl-

Cl-

Na+

Cl-

Dehydration Dehydration

HyperOsHyperOs HyperOs

HyperOs

Water accesst = > 36 hrH2O

Osmotic brain edema - Salt toxicity

PLASMANormoNa NormoNa

N

Ed

ema

Deh

ydr.

BRAIN

AA

AANa+

Cl-

Edema Normal hydr.

HyperOs NormalOs

PLASMANormoNa HyperNa

N

Ed

ema

Deh

ydr.

BRAIN

AA

AA Na+Cl-Na+

Na+

Cl-

Na+

Na+

Cl-

Cl-

Cl-

Na+

Cl-

Dehydration Dehydration

HyperOs HyperOs

Na+

Na+

Cl-

Na+

Cl-

Lesions

• Brain swelling • Cerebrocortical necrosis (occ)

Histology

• Laminar cerebrocortical necrosis• Perivascular eosinophilic infiltrate (Po)

E. Simko WCVM

Osmotic brain edema - Salt toxicity

Diagnosis

• History

• Gross and histologic lesions

• Na level in the brain

E. Simko WCVM

Osmotic brain edema - Salt toxicity

Vasogenic brain edema

The most common type of brain edema

Pathogenesis: damaged BBB

Examples:

Toxins

Inflammatory processes (H. somnus)

E. Simko WCVM

Vasogenic brain edema

White matter Grey matterE. Simko WCVM

• Shigella toxin type II (Edema disease) Po

Fibrinoid vasculitis

• Epsilon toxin (C. perfringens D enterotoxemia) Ov

Symmetrical encephalomalacia

• Fumonisin B1 (Fusarium momiliforme) Moldy corn

Equine leucoencephalomalacia

Toxins

E. Simko WCVM

Vasogenic brain edema - Salt toxicity

Toxin-induced

Necrosis

TraumaThiamine deficiencyLead poisoningSalt poisoningEdema diseaseClostridial eterotoxemiaEquine leucoencephalomalaciaInfarction

Response to injury - Necrosis

Infarction