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.
Bamford classification - TACS
Total Anterior Circulatory stroke
3/3 symptoms
- homonymous hemianopia
- higher cortical disfunction
- sensory or motor disfunction
Usually anterior and middle cerebral arteries.
high mortality
Bamford Classification - PACS
partical anterior circulatory stroke
2/3 symptoms
- motor or sensory deficit
- homonymous hemianopia
- higher cortical disfunction
Usually middle and anterior
Bamford Classification - LACS
Lacunar stroke
isolated sensory or motor disfunction
Small deep arteries (usually subcortical)
Bamford Classification - POCS
Posterior circulatory syndorme
cerebellar (ataxia)
isolated hemianopia
Brian stem signs
- disordered eye movements
Risks for Stroke
- > 55yrs
- atherosclerosis
- Obesity/ high cholesterol
- hypertension
- diabetes
- smoking
- drinking and drugs
Ischemic Stroke
Thrombic - caused by a thrombus (bloodclot) occurring in the carotid arteries supplying the brain.
Arteries narrow due to atherosclerosis (build up of plaque on arterial wall) - sticky catching blood cells and inflamatory response
Hypertension damaging smooth muscle cells lining the arterial walls (wears away and becomes less elastic)
Embolic - Caused by embolism (bloodclot or plaque) broekn away from arterial wall and flows through blood vessel to brain, gets stuck and blocks the flow of blood.
left sided stroke
- Right sided symptoms (hemiparesis, hemianopia, reduced sensation)
- Language Deficit (spoken and written)
- impaired logic and decision making
- move slower, more cautious
Right Sided Stroke
- Left sided symptoms (hemiparesis, hemianopia, sensation)
- Spatial and perceptual loss
- impulsive behaviours
- less aware of their deficits
Haemorrhagic Stroke
Occurs due to hypertension and arterial walls weaken/ thin
Berry aneurism occurs and can rupture causing blood to flow out of vessel, away from what is was meant to supply
Wide spread damage
Increased ICP
1. Subarachnoid ( outside brain issue between pia matter and arachnoid matter)
2. Intracranial
Ischemic Cascade
Death occurs primary at the ischemic Core. - area deprived of blood
The penumbra is the surrounding area at risk of infarction but is salvageable if reperfused quickly.
Then a cascade of events occur which cause neuronal death and apoptosis
Eg. energy falls as no ATP and pumps fail causing calcium build up = Excitotoxicity, cell edema, increasing ICP, mitochondrial disfunction.
Frontal lobe
Responsibility and damage
Responsibility:
- Higher cognitive function
- speech and language (Broca’s area - expressive)
- Mood and personality
- motor function and planning (motor cortex)
- Problem-solving and working memory
Damage:
- Weakness (hemiparesis)
- Poor working memory, logic and problem solving
- Reduced motor planning and function
- depression/ behavioural changes
- Expressive speech aphasia
Parietal Lobe
Responsibility and damage
Responsibility:
- sensory integration from other lobes (proprioception)
- Somatosensory cortex
- understanding and attention
- visuospatial awareness
Damage:
- Deceased or impaired sensation
- poor integration (proprioception)
- decreased attention
- poor visuospatial awareness
- Neglect
Temporal Lobe
Responsibility and damage
Responsible:
- Auditory inforation/ processing
- Formation/ management of memories
- Understanding speech (receptive)
- object/ facial recognition
Damage:
- poor hearing/ deafness
- inability to lay down new memories
- receptive aphasia
- agnosia (poor recognition of objects, faces or task)
Occipital Lobe
Responsibility and damage
Responsibility:
- visual processing
- visuospatial awareness
- visual recognition of objects/faces/colour
Damage:
- poor depth, size and distance awareness (visuospatial deficit)
- blindness/ diplopia/ poor vision
- hallucinations/ epilepsy
Cerebellum
Responsibility and damage
Responsibility:
- Smooth co-ordination of voluntary movement
- maintenance of balance and posture
- tone
- new motor skill/ motor learning
Damage:
- tone deficit
- poor balance / posture
- Ataxia
- decreased fine motor control or motor activity
Basal Ganglia
Responsibility and damage
Responsibility:
- regulation of smooth voluntary and autonomic muscle movements
- Feedbacks signals to motor cortex which excite or inhibit muscle movements (motor control)
Damage:
- Parkinson’s disease
- Oscillating inhabitation/ excitation
- poor control of posture, speech, motor movements
- poor initiation of movement
The Brainstem
Connects the spinal cord to brain and produces the 12 cranial nerves (pons, medulla midbrain)
Responsible for:
- autonomic functions (breathing, HR, digestion)
- sends sensory information to thalamus
Damage:
- deficits to cranial nerves (motor function, swallowing, eye function)
- autonomic disfunction
- high mortality
Blood supply to cerebrum
ACA = anterior and medial aspects (Frontal, parietal)
MCA = lateral aspects of cerebrum and many deep structures ( frontal, temporal, occipital, parietal)
PCA = medial and lateral aspects of posterior cerebrum (occipital, temporal)
All are connected by circle of willis
Circle of willis
To ensure constant and connected blood flow between main arteries and communicating arteries around the brain so O2 and nutrients continue to tissue, despite certain areas which may have reduced flow
2 internal carotid arteries and 2 vertebral arteries form at the base of the brain to create the circle of willis
The vertebral arteries join to create the basilar artery which splits into other including the posterior cerebral artery (occipital, temporal, cerebellum)
The internal carotid arteries split to form the MCA and ACA which supply (frontal, temporal, parietal and part of occipital)
Blood supply to cerebellum
superior cerebral artery (SCA)
anterior inferior cerebellar artery (AICA)
posterior inferior cerebellar artery (PICA)
Stroke milestones
1min sit
- POCS, LACS, PACS = couple of days
- TACS = 3 weeks
10 sec stand
- POCS, LACS, PACS = by 1 week
- TACS = 8 weeks
10 steps
- POCS, LACS, PACS = by 2 weeks
- TACS = 18 weeks
10m walk
- POCS, LACS, PACS = by 3 weeks
- TACs = by 20 weeks (only 30%)
