Pathophysiology Flashcards
The Direct Pathway
The direct pathway is an excitatory pathway which promotes voluntary smooths movements from the basal ganglia. Signals are sent from the motor cortex to excite the striatum then inhibitory signals are sent from the striatum to the globus pallidus internus. Usually the globus pallidus inhibits the thalamus with the release of neurotransmitter GABA. Meaning the thalamus can fire and movement is promoted. (inhibition of the inhibitor = accelerator)
The Indirect pathway
The indirect pathway reduces movement. Signals (glutamate) are sent from the motor cortex to excite the striatum. Then inhibitory (GABA) neurotransmitters are released into the globus pallidus externus which further inhibits the sub thalamic nucleus so that inhibition of the GPI doesn’t occur. As we know the GPI inhibits the thalamus so when it is active it can do so. = reduced excitation of motor cortex
Reduction of Dopamine in Basal Ganglia
The nigrostriatal pathway releases dopamine into the striatum where it bind to D1 and D2 receptors. Dopamine neurotransmitters promote the excitatory pathway and inhibit the indirect pathway = promotes smooth movement.
Reduced dopamine means that the inhibitory (indirect) pathway is not inhibited and fires alongside the direct pathways causing over inhibition = hypo-kinetic tendencies (bradykinesia) and tremor (stop start contractions)
Stages of PD
Prodromal = Before clinical diagnosis, non-motor symptoms (poor sleep and constipation)
Stage one - Mild symptoms, unilateral tremor, beginning of TRAP symptoms
Stage 2 - Mild symptoms, bilateral symptoms, facial changes but still balanced
Stage 3 - moderate symptoms, loss of balance, progression of TRAP
Stage 4 - severe symptoms, unable to stand without assistance
Stage 5 - wheelchair bound as stiffness in legs and weakness make it impossible to stand, hallucinations occur.
Risk Factors to PD
Genetics: alpha-synucleic protein misfolds and Lewy bodies can form within the neurons, Effects integrity of the cell:
- mitochondrial miss function (neuro inflammation)
- activity and release of neurotransmitter dopamine
- normal protein recycling
Environment: Pesticides and pollution – - (seen higher levels in cities like china) - - oxidative stress (cascade of effects, neuro inflammation and neural death)
Age and Gender = >60 and male
Immune Response in MS
The Brain and neurons within it are protected by the BBB. It only allows molecules with the correct ligand or surface molecule to pass. Once a T-cell enters the brain it is activated by myelin and release chemical cytokines which directly damages oligodendrocytes and myelin, and initiates an immune response and dilates the blood vessels which allows more cells to pass.
B-cells and WBC Macrophages come
B-cells release antibodies to mark the myelin and oligodendrocytes as foreign for the Macrophages to perform phagocytosis and engulf/ digest the myelin and oligodendrocytes.
Proliferation of astrocytes occurs and lay down fibrous scar tissue causing lesion on the axons = irreversible damage, no remyelination.
What is PD
Parkinsons Disease is a progressive neurodegenerative disease caused by the degeneration of neurotransmitter dopamine within the basal ganglia.
What is MS
Multiple Sclerosis is an autoimmune and neurodegenerative disease caused by the the immune system attacking myelin within the CNS. Results in poor or disrupted communication between neurons.
What is Myelin
Myelin is formed by oligodendrocytes in the CNS and shawm cells in PNS. An insulating and protective layer which is wrapped around the axon to speed up electrical nerve impulses along an axon though saltatory conduction.
= When signal jumps between gaps in myelin (nodes of ranvier) and a new action potential is formed at each gap.
Why do stages occur in MS
Attacks happen in bouts.
Regulatory T-cells can come in to inhibit immune response from other cells and decrease inflammation
Early on oligodendrocytes can heal and replace the damaged myelin before permanent lesions occur.
Later oligodendrocytes die off, remyelination stops
= irreversible damage due to loss of axons
This demyelination and remyelination is what causes the relapse of symptoms and then period of remission where symptoms better (or stay the same)
What are the stages in MS
Benign - Very mild, shows some symptoms but no attacks
Primary progressive - steady increase in disability/ symptom without attacks
Relapse Remitting - (80-95%), random attacks followed by periods of partial or complete remission
Secondary progressive - (50% move into after 10-15yr of RRMS), initial relapse remitting followed progressive disability without remission
Causes of MS (risks)
Genetics: The human leukocyte antigen is associated with effects in immune response in MS
Infection: Epstien-Barr syndrome: mono/ herpes virus associated
UV radiation and vitamin d deficiency (increased prevalence in northern hemispheres)
Life-style: Female, 20-50yrs, smoking, obesity
Diagnosis of MS
At least 2 attacks and 2 separate lesions
- MRI/CT scan for lesions/ White matter plaques
- Lumbar puncture to see if increased antibodies in CSF = immune response)
What is a stoke
The brain needs a constant supply of oxygen and nutrients to function (as neurons are exclusively aerobic). A stoke is caused by a disturbance in cerebral function lasting for > 24hrs due to decreased blood flow. Cell function ceases after 1min with irreversible damage after 4mins. (death)
What is a TIA
Transient Ischemic Attack (mini stroke)
Disruption of blood to the brain with symptoms lasting <24hrs.
13 x more likely to have a stoke in future.
