Neuropathology Flashcards
What is a Lysosome
“Digestive system” of cell. Small membrane-bound organelles containing hydrolases that degrade macromolecules arriving by endocytosis, phagocytosis or autophagy
What’s the difference between phagocytosis and pinocytosis?
Phagocytosis is the cytosis of a solid particle whereas pinocytosis deals with (extracellular) fluids
What’s the difference between a phago/pinocytosed vesicle and receptor-mediated endocytosed vesicle
Receptor-mediated endocytosed vesicles have coat proteins on the outside becoming a coated vesicle
What is the name of a phagocytosed particle engulfed in a vesicle
Phagosome (cytosome)
What is an autophagosome
?
What gets packaged in vesicles
Damaged organelles, lipids, denatured proteins (happens around pH 6)
What happens to lysosomes in the rER before they’re finally packaged
They’re fly soulmates and tagged with mannose-6-phosphate ligand which allows the package to be easily picked up by cells with mannose-6-phosphate receptors
How many enzymes does a lysosome contain
Over 50
Brief description of what happens if lysosomes lose function
Accumulation of substrate that’s meant to be broken down. This can affect the brain, bones, muscles etc.
How many lysosomal storage disorders are there
Over 50
What does MPS disease stand for
MucoPolySaccharide Disease
What is the cause of Mucopolysaccharide disease
Caused by enzymatic defect in the breakdown glycosaminoglycans (long chain sugars) —> different GAG sugars being stored
What happens in MPS that causes the storage of Heparin Sulphide?
exhibit lysosomal swelling l, neuroinflammation, sever brain dysfunction and behavioural problems.
What’s the name for MPS type 1
Hurler’s syndrome
What is hurlers syndrome
An autosomal recessive disease resulting in progress neurodegeneration. Some treatments are available through HSCT and ERT
What are some symptoms of Hurlers syndrome (MPS Type 1)
Cloudy corneas, deafness, intellectual disability, halted growth, bone and joint problems
What’s the name MPS type 3
Sanfilippo disease
Characteristics for MPS Type 3
Sanfilippo disease affects the first decade of life, leads to death in adolescence and progressive cognitive function & latter mother decline.
Stores heparin sulphide and also secondary storage if GM gangliosides
What can the storage of GAG sugars lead to
Lysosomal swelling and dysfunction. Can be leaked into bloodstream to cause problems for immune system
There is a natural multi step process of heparin degradation. What happens if one of these steps/enzymes is disrupted
Accumulation of HS over time leading to storage of GAGs
How can the sulphation heparin sulphide be monitored
Disaccharide analysis
What do we see in the neuropathology if lysosomal disorder
Enlarged lysosomal compartment due to lysosomal swelling
What can MPS disease lead to the secondary storage of
GM2 ganglioside
What other organelle may we see under the microscope when looking at neuronflamation
Microglia - proliferate to deal with presence (Depredation) of GAGs - sort of like macrophages
What is cross-correction is enzyme production and uptake
10% of enzyme produced is released from cell, taken up via mannose-6-phosphate receptors by RM endocytosis and secretion is determined by presence of one single peptide on the enzyme
Why can’t you just deliver the enzyme into the bloodstream as a treatment
Because the bbb limits it making the process ineffectual and the immune system could recognise it as foreign and degrade it (a way to avoid this is HSCT so the immune system changes with it)
Why doesn’t ERT work with sever MPS disorders
Enzymes can’t pass bbb from blood stream to brain where they’re needed for hurlers and sanfilippo.
How do you overcome the bbb to deliver an enzyme treatment
Physical injection or overproduction of enzyme
What ERTs are available atm
Direct enzyme delivery to brain through spinal cord, monthly injections and intra CSF delivery in MPS nice corrects disease if delivered early enough (in clinical trials)
Intracranial enzyme - direct injection to brain
Modifying enzyme allowing it to pass through bbb
How does the skull cope with increased pressure and how does this affect a person in the long run.
Brain is able to push some CSF or blood out of the skull. Eventually the process fails at about 30mgH2O intracranial pressure where the pressure starts to rise rapidly again.
Pats of the brain may herniate or get squeezed out of profaned or over rigid folds of the dura.
What are the effects of an increase in cerebral pressure
As pressure increases, perfusion pressure decreases leading to decreased cerebral blood flow —> hypoxia or cell death
Define hypoxia
?
Define perfusion
?
What are the 3 layers called that cover the brain
Dura mater, arachnoid, pia mater (from top to bottom) - collectively the meninges
What is obstructive hydrocephalus
When the flow of CSF is blocked anywhere along it’s pathway, obstructive hydrocephalus develops rapidly
Where are CSF samples taken from
Lumbar puncture (lower spinal chord)
How are blood vessels in the brain unique
Have thinner tunica media and no external elastic lamina - have to be sensitive and able to change the construction and dilation quickly & easily
What is the Blood Brain Barrier
Separation of circulatory blood and extra cellular fluids - blocks diffusion if microscopic objects e.g. bacteria and large hydrophilic molecules into CSF
Will allow small molecules like o2, co2, hormones etc.
Why does dinner is have a limited pthophysiology
Because it’s only really studied at onset
Does havin amyloid plaques or tau deposites in brain mean you will develop dimentia
No not necessarily
What are two standard procedures when physically examining the brain
Covering of brain I.e. the meninges Gurus patterning (mapping)
What is the name of the peak of a deep fold in the brain
A gyrus
What is the name of the trough of a deep fold in the brain
The sulcus
Why is cranial nerve examinations good for tricky diagnostics
Symptoms may not always be enough pointing in the direction of a route cause whereas if we know that sight has been affected (as an affect of nerve damage), we also know the nerve that’s linked to it and can help find the route cause
What features is the occipital lobe linked with
Vision
What features is the parietal lobe linked with
SENSORY Intelligence Language Reading Sensation
What features is the temporal lobe linked with
Behaviour Hearing Memory Speech Vision
What features is the frontal lobe linked with
MOTOR Behaviour (emotion) Intelligence Memory Movement Problem solving
What features is the cerebellum linked with
Balance
Coordination
What features is the brain stem linked with
REGULATES BASIC BODY FUNCTIONS Blood pressure Breathing Consciousness Heartbeat Swallowing
What are the 3 different body and brain planes
Sagittal, coronal, transverse
Name some temporal lobe disease symptoms
Hearing disturbances
Alteration to personality and behaviour
Language comprehension problem
Name some techniques to study brain function
Case study patients Remove part to examine Stimulate and monitor Record activity -fMRI -MRI
What does the fusiform face area do and where is it
Located in temporal lobe, when stimulated it leads to movement in facial muscles
Symptoms of ICP Intercranial pressure
Bradychardia Papilloedema Headaches in morning Drowsiness Seizures
True or false: The brain has no nerve sensors with which to feel pain or pressure
True
Describe what a grade is in the WHO grading system
A grade is the degree to which a tumour cell is different from a normal cell under the microscope
Describe a Grade 1 Tumour
Benign cytological features
Describe a Grade 2 Tumour
Moderate cellularity - no anaplasia or mitotic activity
Describe a grade 3 tumour
Cellularity, anaplasia, mitosis
Describe a Grade 4 Tumour
Grade 3 + vascular proliferation and necrosis. Permeate adjacent to normal brain tissues. Blastomas.
Most malignant, highly proliferating
Define necrosis
?
What variables can affect the survival rate with a tumour
Age, severity of metastasis, location and size, grade and type
True or false: surgery alone can be a sufficient treatment for Grade 1 Tumours
True
True or false: surgery alone can be a sufficient treatment for Grade 4 Tumours
False
What is a glioma?
50% of all primary Tumours
Give an example of a non-glial brain tumour
Meningioma: very common meninges tumour
What organisms can infect the brain other than the usual 3
Parasites and Prions
What is meningitis
Inflammation of meninges caused by bacteria
What is encephalitis
Inflammation of brain (general term) - meningitis is a type of encephalitis
What is the process of diagnosing meningitis
Same ole of CSF through lumbar puncture, ID bacteria, give treatment. Prognosis: untreated —> generally fatal
Common cause of meningitis in neonates?
E. Coli
Common causes for meningitis?
N. Meningitidis, S. Pneumoniae
What are the 3 types of meningitis
Pneumococcal, chronic, cryptococcal (fungal)
Describe the characteristics of a Toxiplasmosis gondii infection
Limited to immunosuppressed/compromised people I.e. most common cause of mass lesions in HIV infected patients. In most cases causes necrotising cerebritis
What is fatal familial insomnia
A prion disease affecting familia, thalamus disorder
Name some diseases associated with CNS deredatation
Disorders of Myelin or neuronal degenerations
Myelin disorders - Describe the difference between demyelinating (MS) and dysmyelenating (Leukodystrophies)
?
What are the characteristics of neuronal degeneration
Primary degeneration happens either globally (e.g. Lew my body, Alzheimer’s) or selective/system (e.g. Parkinson’s or Huntington’s)
Secondary is based on metabolic storage, toxic, infections, nutrition or even alcohol and b12 deficiency
Describe briefly what MS is
An autoimmune response primarily against CNS myelin (white matter). Regions of white demyelination are called plaques
What are plaques in the brain
Regions of demyelination white matter
True or false: plaques in the cortex may lead to dementia’s
True
True or false: plaques in the basal ganglia and brain stem can lead to dementia’s
False, they lead to Parkinsonian diseases
What are the primary causes of denial CNS degradation
Alzheimer’s, left body, Huntington’s, picks disease
What are some secondary causes to senile CNS degradation
Stroke, infections, drugs, toxins, vitamin deficiency
What are some pathological hallmarks of CNS degradation
Deposition of amyloid plaques around blood vessels and neurons
Abnormal form of microtubule protein (tau) in neurons neurofibrillary intracellular tangles.
Degeneration starts in hippocampus
Use Silver stain
What is silvers stain used for
?
Characteristics of frontotemporal dementia (& picks disease)
Personality changes followed by memory loss, affected personality, behaviour and speech
Pathology: neurons with round intracytoplasmic Picks bodies
Characteristics of Vascular dementia
Associated with multiple undercard, he served the name multiple infarct dementia.
2nd most common form of dementia after Alzheimer’s
What are Lewy bodies and Tau
Irregular densely packed proteins that develop inside nerve cells and disrupt neurosignalling causing cells to die
Found in cortex or brain stem
What are neurofibrillary tangles
Primary marker of Alzheimer’s disease, tau protein stabilises the structure of microtubules so when aggregates of hyperphosphorylated tau protein form away from the tubules, they destabilise and start to fall apart.
