Neuropathology Flashcards
What is Gliosis?
Astrocytes hypertrophy (upregulation of astrocytic activity) and increase GFAP immunoreactivity in response to both acute and chronic insults.
-Infiltration neoplasm, ischaemia, infection
Gliotic tissue is firm and appears grey.
What is normal intracranial pressure?
- Within the intact skull, there are 3 major components of intracranial pressure: the brain, the CSF and blood.
- Any increase in volume of one of these 3 components will produce an increase in ICP, unless a compensatory reduction in one of the other components occurs
- Normal upper limit of ICP is 2.7kPa (reduce CSF, collapse venous sinuses)
What are the common causes of raised ICP?
- Intracranial expanding lesions – tumour, haematoma, abscess
- Hydrocephalus (excessive CSF= ventricular dilatation)
- Cerebral oedema – an increase in the water content of the brain, due to dysfunction of the blood-brain barrier. This can be localised (eg around tumours) or generalised(eg following severe head injury or in hypoxic brain damage)
What is the normal cerebral blood flow?
Human cerebral blood flow =Overall- 50 ml/100g per minute =Grey matter- >80 ml/100g per minute =White matter- 20-25ml/100g per minute -The cerebral metabolic rate is higher for infants (and also in other species with small brains)
Examples of cerebrovascular disease
- Strokes can be thrombo-embolic or haemorrhagic (20%).
- In thrombo-embolic disease symptoms are determined by the vessel involved.
- When there is hypotension watershed infarcts can develop.
- Cardiac arrest results in global brain injury (hypoxic-ischaemic encephalopathy HIE)
What is Subfalcine herniation?
-Medial direction/ midline shift of the ipsilateral cingulate gyrus beneath the free edge of the falx cerebri due to raised intracranial pressure.
What is axial displacement?
Diencephalic structures pushed downwards by brain swelling
Where are primary hypertensive haematomas usually found in the brain?
Basal ganglia
Brainstem and cerebellum
What occurs at a microscopic level in the brain vessels in hypertension?
Lipohyalinosis/ small vessel disease accounts for defects in vessel resulting in parenchymal haemorrhage
-Large vessel occluded by degenerative features caused by long-standing chronic hypertension
What are the causes of parenchymal brain haemorrhage?
- Hypertension
- Vascular malformation
- Neoplasia (metastatic, primary gliomas like oligodendrocyte)
- Trauma (more superficial)
- Cerebral amyloid angiopathy (older patients, consequence of proteins associated with Alzheimer’s- lobar haematomas)
- Iatrogenic, other blood dyscrasias (anticoagulants)
What are Border zone infarcts?
- Border zone infarct develop at interface between anterior, middle and posterior cerebral artery territories
- Consequence of hypertension
What are the areas of Selective Vulnerability to lack of blood flow?
- Hippocampus- sector CA1 is most vulnerable, sector CA2 least so.
- Cerebral cortex- neurones of layers 3, 5 and 6 are most vulnerable. Damage is most pronounced within the depths of sulci and posteriorly within the cerebral hemispheres (triple watershed zone).
- Basal ganglia (including thalamus)- variable.
- Cerebellum- Purkinje cells.
- Brainstem- Brainstem nuclei tend to be relatively preserved in adults, but when they are affected sensory nuclei are more susceptible than motor nuclei
What are the consequences of cardiac arrest and global cerebral ischaemia?
- Cessation of blood to brain= irreversible neuronal damage
- Lack of blood and oxygen to neurones (cytoplasm red in red cell change)
- Build up lactic acid around neurones usually removed by blood from perineuronal environment
What are the causes of subarachnoid haemorrhage?
- Ruptured aneurysms
- Trauma
What is a cerebral aneurysm?
- Swelling of artery at a junction
- Can rupture and cause intracerebral or subarachnoid haemorrhage (aneurysm of MCA)
What organisms target the NS for infection?
-Viruses eg herpes, CMV, measles, rabies, HIV -Bacteria eg meningococcus, listeria, m. tuberculosis -Protozoa eg amoeba, toxoplasma, pl. falciparum (malaria) -Metazoa eg echinococcus (hydatid cyst) -Fungi eg aspergillus, candida -Prions
What are the modes of transmission of infection to the NS?
- Blood borne: septicaemia, viraemia, infected blood cells (Trojan horse), embolisation (IV drug use, transfusion)
- Direct spread: local source of infection (mastoid abscess, frontal sinus infection, maxillary sinus infection)
- Trauma: breaching NS coverings (incl neurosurgery)
- Transplants (immune suppressed)
- Pregnancy-related vertical transmission
- Original source of infection may include contact, inhalation, sexual transmission
What are the foetal infections of CNS?
- Rubella (deafness, blindness, microcephaly)
- CMV (microcephaly)
- Toxoplasma (microcephaly)
- Syphilis (tertiary forms include GPI, tabes dorsalis and meningovascular syphilis)
- (HIV)
What organisms cause meningitis?
-Bacteria
=Infants: Group B Streptococcus, E. coli, Listeria
=0-4yrs: Haem. influenzae, Strep. pneumoniae, Myco. tuberculosis (in high prevalence countries)
=0-25 yrs: Neiss. meningitidis
=Older adults: Myco. tuberculosis (in low prevalence countries)
=IV drug abuse: Staph. aureus
-Viruses
=Children: Enteroviruses (Coxsackie, Echo)
=Adults: Herpes viruses, Mumps
-Immunosuppressed
=Cytomegalovirus, =cryptococcus
What are the viral infections of the NS?
-Meningitis
eg echoviruses, coxsackie, herpes simplex, mumps
-Acute encephalitis
eg herpes simplex, CMV, varicella zoster virus, rabies (rubella in fetus)
-Subacute encephalitis
HIV
-Demyelination
JC virus (progressive multifocal leucoencephalopathy)
-Delayed, reactivated
Varicella zoster virus
Describe Herpes Simplex Encephalitis
-Used to have high mortality
-Aciclovir= mortality dropped
=Early treatment vital
-Necrotising damage
-Hippocampus and medial temporal lobes affected
-Survivors have memory problems
Describe Rabies
Enter body through bite wound
Crawls up peripheral NS to CNS
Fatal when in CNS
Affects neurons with Negri Body (viral protein)
What are the common Protozoal and Metazoal infections?
Rare in UK
Toxoplasma (foetal/ neonatal/ immunosuppressant like HIV)
=cysts in ventricles
-Cerebral malaria
=plasmodium infection
=acute brain swelling and widespread haemorrhage
What are the fungal infections of the CNS?
- Candida
- Aspergillus
- Cryptococcus
