Neurological conditions

Question 1

what is a neuro degenerative condition? list a few.

Answer 1

it is where cells in the central nervous system stop working or die. For example, Dementia, alzheimer, parkinsons. They are all associated with cognitive decline.

Question 2

what is memingitis? the cause? how does it put pressure on the brain?

Answer 2

inflammation of the meninges. Bacterial meningitis is caused by bacteria getting into the cerebral spinal fluid. This puts pressure on the brain in 3 ways: inflammatory response, build up of pus, inability to reabsorb cerebral spinal fluid to reduce pressure.

Question 3

how are amyloid plaques formed

Answer 3

Amyloid plaques are deposits of beta amyloid that accumulates in the tissues of the brain, outside the tissue cells. This happens by a variety of enzymes separating the beta amyloid from the amyloid precursor protein in the neuron. This is secreted out of the neuron and sits in the intracellular space, where it can fold into the fibrils that make up the amyloid plaque.

Question 4

what is the amyloid cascade hypothesis

Answer 4

The amyloid cascade hypothesis describes how beta amyloid could be a key trigger of the disease because the amyloid precursor protein is created by a gene variant, and if beta amyloid starts to creates plaques in uninfected areas then the disease worsens. It also leads to the deposition of tau protein.

Question 5

describe how tau protein forms neurofibrillary tangles

Answer 5

• Tau protein is encoded by the MAPT gene, which stabilises the microtubule network in axons. Microtubules are important in distributing proteins and neurotransmitters around the cell. So, if tau isn’t fully functional then neither will the distribution of neurotransmitter around the axon. Tau protein is usually soluble in the cytoplasm, but becomes insoluble when it is highly phosphorylated (chemical groups inappropriately added to it). This creates neurofibrillary tangles, which is the main cause of neurodegeneration as brain signals cannot be transmitted as easily. They can be spread across neurons, because filament fragments fan travel across a synapse and seed into the connecting neuron. It leads to neuronal death.
  The formation of neurofibrillary tangles is much more clearly correlated with the progression of Alzheimer’s disease than amyloid plaques.  

Question 6

what does taupathy do to neurons?

Answer 6

It disrupts the functioning of the cytoskeleton, disrupts protein distribution around the cell, and disrupts the synapse function and formation. These things lead to neuronal death.

Question 7

what is the role of inflammation in Alzheimer’s disease?

Answer 7

as a response to try to slow or prevent Alzheimer’s disease, the body creates an inflammatory response. Microglia and astrocytes are activated. Activated microglia inhibits seeding of both beta amyloid ant tau protein, and can destroy amyloid beta in the brain tissue. However, destroying it releases damaging inflammatory mediators

Question 8

what is the role of astrocytes?

Answer 8

it helps maintain the integrity of the blood-brain barrier, controls the physiological environment for the brain cells, it also creates scar tissue

Question 9

what is the role of microglia?

Answer 9

it monitors health of tissues of the brain, aids the inflammatory response, acts a bit like macrophages- they are central to the development of inflammation in the brain

Question 10

what is primary brain trauma?

Answer 10

the initial insult. The processes of physical displacement of the brain

Question 11

what is secondary brain trauma?

Answer 11

the body’s response to the trauma such as the inflammatory response.

Question 12

what is ischemia?

Answer 12

where blood flow, and so oxygen and nutrients, are restricted or reduced in a part of the body.

Question 13

what is the Monroe-Kellie Doctrine?

Answer 13

describes the relationship between the contents of the cranium and intracranial pressure.

Question 14

what is apnoea?

Answer 14

high pressure in the brain stem which causes differences in the normal rate of respiration.

Question 15

what is herniation?

Answer 15

the effects of huge intracranial pressure. It is where pressure inside the skull causes brain tissue to move.

Question 16

what is a brain hemorrhage?

Answer 16

= a bleed in the brain

Question 17

what happens during the body’s response to brain trauma?

Answer 17

Cerebral spinal fluid can be lost if there is a perforation, or the distribution of it may be altered. this can lead to a lack of oxygen and nutrients to the brain as well as altered pressure. The lack of nutrients causes mitochondrial dysfunction, so other cells cant function properly due to a lack of atp (energy). As the atp runs out, neurons produce an increasing amount of glutamate and create a positive feedback loop that results in a toxic environment where neurons die. Programmed cell death can also happen. So, there is a risk for cognitive dysfunction. A person who survives primary brain trauma does not always survive secondary.

Question 18

what changes happen in the brain due to ageing

Answer 18

Neuronal loss begins at 20 years of age, and by 90 you have 10-15% loss of brain tissue. This is associated with the gradual loss of function as you age. We also develop pigmentation of neural tissue as we age, which is connected with the development of neuronal plaques.

The hippocampus loses mass as it doesn’t produce as many new cells in the brain, and the connection between the cells is weakened- which affects memory. Autonomic centres respond less rapidly, due to the brain stem slowing process down. There is reduced integrity of the blood brain barrier, so the body isn’t as protected against pathogens. Neurotransmitter production is reduces, so the regulation of proteins inside cells is reduced and it becomes disorganised.

Question 19

tell me about the blood brain barrier. function? where is it located?

Answer 19

– helps to isolate the brain from the circulatory system to protect the brain from toxins, pathogens, and blood components. As well as it being a physical barrier, it is also a biochemical barrier because astrocytes wrap around blood vessels to control the transfer of nutrients. The blood brain barrier is absent in the choroid plexus and posterior pituitary gland.

Question 20

describe the gross anatomy of the meninges.

Answer 20

It is located inside of the skull, hugging the brain, and there are 3 layers. The most inner is the pia mater, which is a nutritive layer touching the surface of the brain. The middle layer is the arachnoid mater, which is a tough layer that holds the cerebral spinal fluid close to the pia mater. The dura mater is the outermost layer that lines the cranium.

Question 21

MENINGITIS. what is it? what happens? whats the mortality like?

Answer 21

= inflammation of the meninges

It particularly effects the arachnoid and pia mater layers of the meninges because they sit next to the subarachnoid space, which contains the cerebral spinal fluid. Bacteria invades the blood stream and gains access to cerebral spinal fluid, through sites of infection or defects in the blood brain barrier. Bacteria releases toxins which damages or kills neurons, triggering an inflammatory response (with leukocytes), putting pressure on the brain. Intracranial pressure further increases because pus accumulates in the subarachnoid space from dead immune cells, and this blocks the reabsorption of cerebral spinal fluid into the circulatory system- again increasing pressure. Neuronal damage from meningitis can lead to memory loss particularly if the hippocampus is affected.

Bacterial meningitis is caused by a variety of different bacteria around the world. There are differences in mortality rates due to access to healthcare, age etc. There is also increasing antibiotic resistance to meningitis, which is a significant issue when trying to treat it.

Question 22

describe intracranial pressure and the compensation involved

Answer 22

Cranial volume is fixed at 1700ml, so the total volume of brain tissue, blood, and cerebrospinal fluid needs to equal this. If one of these things has an increased volume, the others need to compensate accordingly or the pressure will be too large. For example, inflammation or a brain tumour would increase tissue volume. Reduced drainage of cerebral spinal fluid or a blockage would increase its volume (these can also be caused by a tumour). Heart failure or hypercapnia (local vasodilation) can increase blood volume.

To compensate for the pressure, there either needs to be increased venous drainage or increased cerebral spinal fluid drainage. This will only help to a point.

Question 23

what is crushing’s triad?

Answer 23

it describes the 3 symptoms of a person who likely has too high intracranial pressure. The first observation is that the patient will have a rising blood pressure. This is because once the hypothalamus becomes ischemic (lacks oxygen and nutrients), the sympathetic nervous system is activated and peripheral vasoconstriction increases blood pressure. Secondly, the patient will have a slowing pulse. This is because the increase in blood pressure activates pressure receptors, which will lead to parasympathetic compensation- so the output of the heart is adjusted and the pulse slows. Finally, the patient will have periodic or slowing respiration. This is because the increase in blood pressure causes pressure on the brain stem, which usually controls the rate and characteristics of breathing, therefore we see slowing respiration.

Question 24

what happens if intracranial pressure gets too high?

Answer 24

tissue of the brain is displaced- this is called a herniation. This can cause death.

Question 25

INTRACRANIAL PRESSURE. cranial volume, compensation, cushing’s triad

Answer 25

Cranial volume is fixed at 1700ml, so the total volume of brain tissue, blood, and cerebrospinal fluid needs to equal this. If one of these things has an increased volume, the others need to compensate accordingly or the pressure will be too large. For example, inflammation or a brain tumour would increase tissue volume. Reduced drainage of cerebral spinal fluid or a blockage would increase its volume (these can also be caused by a tumour). Heart failure or hypercapnia (local vasodilation) can increase blood volume.

To compensate for the pressure, there either needs to be increased venous drainage or increased cerebral spinal fluid drainage. This will only help to a point.

Crushing’s triad describes the 3 symptoms of a person who likely has too high intracranial pressure. The first observation is that the patient will have a rising blood pressure. This is because once the hypothalamus becomes ischemic (lacks oxygen and nutrients), the sympathetic nervous system is activated and peripheral vasoconstriction increases blood pressure. Secondly, the patient will have a slowing pulse. This is because the increase in blood pressure activates pressure receptors, which will lead to parasympathetic compensation- so the output of the heart is adjusted and the pulse slows. Finally, the patient will have periodic or slowing respiration. This is because the increase in blood pressure causes pressure on the brain stem, which usually controls the rate and characteristics of breathing, therefore we see slowing respiration.

If the intracranial pressure becomes too severe, tissue of the brain is displaced- this is called a herniation. This can cause death.

Question 26

what is Alzheimer’s disease and its gross anatomy?

Answer 26

Alzheimer’s disease is the most common cause of dementia and is associated with cognitive impairments. Reduced brain function happens due to a loss of tissue in the brain which causes there to be more space between the remaining brain tissue. The loss of brain tissue in the Para hippocampal cortex causes loos of memory as it is a key area in coding and forming memories.

Question 27

ALZHEIMER’S DISEASE. gross anatomy, amyloid plaques, amyloid cascade hypothesis, tau protein, neurofibrillary tangles

Answer 27

Alzheimer’s disease is the most common cause of dementia and is associated with cognitive impairments. Reduced brain function happens due to a loss of tissue in the brain which causes there to be more space between the remaining brain tissue. The loss of brain tissue in the Para hippocampal cortex causes loos of memory as it is a key area in coding and forming memories.

On a microscopic level, there are amyloid plaques and neurofibrillary tangles.

Amyloid plaques are deposits of beta amyloid that accumulates in the tissues of the brain, outside the tissue cells. This happens by a variety of enzymes separating the beta amyloid from the amyloid precursor protein in the neuron. This is secreted out of the neuron and sits in the intracellular space, where it can fold into the fibrils that make up the amyloid plaque. The amount of amyloid plaque does not correlate with the intensity of the clinical signs of Alzheimer’s disease – there could be strong symptoms but few plaques. This means the cause and effect relationship isn’t strong, but we do know the plaques are present in the disease.

The amyloid cascade hypothesis describes how beta amyloid could be a key trigger of the disease because the amyloid precursor protein is created by a gene variant, and if beta amyloid starts to creates plaques in uninfected areas then the disease worsens. It also leads to the deposition of tau protein.

Tau protein is encoded by the MAPT gene, which stabilises the microtubule network in axons. Microtubules are important in distributing proteins and neurotransmitters around the cell. So, if tau isn’t fully functional then neither will the distribution of neurotransmitter around the axon. Tau protein is usually soluble in the cytoplasm, but becomes insoluble when it is highly phosphorylated (chemical groups inappropriately added to it). This creates neurofibrillary tangles, which is the main cause of neurodegeneration as brain signals cannot be transmitted as easily. They can be spread across neurons, because filament fragments fan travel across a synapse and seed into the connecting neuron. It leads to neuronal death.

The formation of neurofibrillary tangles is much more clearly correlated with the progression of Alzheimer’s disease than amyloid plaques.