Cause of Every Condition

Question 1

What causes epileptic seizures

Answer 1

Imbalance of excitatory and inhibitory neurotransmitters leading to runaway excitation leading to a sudden synchronization of brain neurons

Question 2

What does GABA binding to its GABA-A lead to

Answer 2

Influx of Cl ions into neuron and hyperpolarization which decreases action potential

Question 3

What causes MS

Answer 3

T-cells with certain expressed ligands can enter the BBB, once inside pattern recognition receptors can bind to myelin and cause an immune response releasing cytokines which recruits more immune cells, these cells then attack the myelin, and the cytokines also attack oligodendroctyes which produce myelin in the CNS, BBB also now because leakier meaning B-cells can now enter and making antibodies against myelin and oligodendrocytes, this leads to scar tissue later forming where myelin was attacked called plaques causing the symptoms of MS

Question 4

What causes schizophrenia

Answer 4

Increased dopamine in mesolimbic pathway leads to positive symptoms

Decreased dopamine in mesocortical pathway leads to negative symptoms

When you take antipsychotics you have decreased dopamine in nigrostriatal pathway leading to extrapyramidal symptoms

Antipsychotic lead to decreased dopamine in tuberoinfundibular pathway meaning increased prolactin which leads to amenorrhea, galactorrhea and gynecomastia

Question 5

Why does bipolar disorder happen

Answer 5

You have increased dopamine in mesolimbic pathway but not too much where it causes positive symptoms of schizophrenia but instead causes Mania

You have decreased dopamine in mesocortical pathway which causes the depressive episodes

Question 6

What are the theories that give an idea of what causes depression

Answer 6

HPA axis dysregulation (hypothalamus - pituitary axis) - leads to release of excess cortisol in pateints with depression

Monoamine-deficiency theory - lack of serotonin, noradrenaline and dopamine causes depression

Question 7

What causes Parkinson’s disease

Answer 7

Decreased amount of dopamine in the brain particularly in the nigrostriatal pathway most likely due to apoptosis and necrosis of dopaminergic neurons (the ones going from the substantia niagra pars compacta) which can occur because of:
- protein misfolding, aggregation and toxicity
- defective proteolysis
- mitochondrial dysfunction
- oxidative stress

Question 8

Why is the apoptosis or necrosis of substantia niagra pars compacta dopaminergic neurons cause the symptoms of Parkinson’s

Answer 8

Dopamine released from the SN pars compacta goes to two dopamine receptors, D1 which excites the direct pathways and D2 which inhibits the indirect pathways. If there is less dopamine being produced it means now there is less excitation of the direct pathway (meaning it’s harder to start movement) and no more / less inhibition of the indirect pathway meaning it’s a lot harder to prevent stopping (like the indirect pathway is not longer regulated it just keeps on inhibiting movement too much.) both leading to the symptoms of Parkinson’s disease

Question 9

What is repeated in Huntington disease

Answer 9

CAG nucleotide (glutamine)

Question 10

Is Huntington disease autosomal dominant?

Answer 10

Yes

Question 11

Where is the huntington gene found

Answer 11

In chromosome 4

Question 12

What happens in Huntington disease

Answer 12

Nucleotides CAG are repeated 36+ times in people with Huntington’s disease causing them to have an abnormally long Huntington protein, this protein then aggregates (builds up / collects) in the caudate nucleus and putamen (striatum) of the basal ganglia causing neuronal cell death leading to an imbalance of the direct and indirect pathway, it mainly causes a breakdown of d2 receptors, that means all the dopamine goes to the direct pathway causing its symptoms. Antipsychotics block dopamine receptors which is why they can be used to treat Huntington’s disease.

Question 13

What causes motor neuron disease

Answer 13

Progressive degeneration of both upper and lower motor neurons

Question 14

Most common motor neuron disease

Answer 14

ALS (amyotrophic lateral sclerosis)

Question 15

What causes corticobasal syndrome and specifically alien hand syndrome

Answer 15

Corricobasal syndrome is a neurodegenerative condition caused by progressive damage to specific areas of the brain, for AHS the most common affect areas are the corpus callosum, medial frontal lobe and parietal lobe

Question 16

What is dementia

Answer 16

Dementia isn’t a disease it’s a broad umbrella term that describes a group of symptoms that occur when brain function declines such as memory loss, confusion, changes in behavior, language or understanding etc

E.g Alzheimer’s or Lewy bodies causes it

Question 17

What is the stage before dementia

Answer 17

Mild cognitive impairement

Question 18

Why does memory, reasoning and processing speed decrease as you age?

Answer 18

As you age there is a decrease and grey and white matter volume so you have less synaptic density less synaptic transmission leading to these symptoms

Question 19

What is the cholinergic hypothesis of Alzheimer’s disease

Answer 19

In Alzheimer’s patients you have deficits in choline acetyltransferase which is needed for synthesis of acetylcholine, you also have loss of cholinergic cells from nucleus basalis of Meynert which is the main area of the brain that produced Ach. Acetylcholine helps with memory and attention so deficits cause memory problems

Question 20

How did the amyloid cascade hypothesis first come to be

Answer 20

Came about because it was observed that people with Down syndrome developed Alzheimer’s disease much earlier (40s instead of 70s or 80s). This is because the APP gene which produces amyloid precursor proteins (then leads to production of beta amyloid) is located in chromosome 21 which people in down syndrome have 2 of.

Question 21

What is the amyloid cascade hypothesis

Answer 21

In the cell membrane sits the amyloid precursor protein which is thought to help the neuron grow and repair. It is normally broken down by alpha and gamma secretases which produces normal soluble products but when beta-secretase breaks down amyloid precursor protein it instead leads to the product amyloid beta, which clumps up to produce beta-amyloid plaques outside of neurons, these beta-amyloid plaques can disrupt communication between neurons leading to brain function impairment seen in Alzheimer’s

Question 22

What genes affect beta amyloid production and how

Answer 22

Mutations in:
- APP gene - leads to more amyloid precursor protein
- PSEN 1 & 2 - genes that alter secretase activity leading to increased beta amyloid production

APOE e4 - gene which is involved in beta amyloid clearance, people with the APOE e4 gene have a clearance system that sucks so you have more beta amyloid plaques

Question 23

What is the Icelandic mutation

Answer 23

A mutation in the APP gene that leads to less amyloid precursor protein produced

Question 24

Facts that go against the amyloid cascade theory

Answer 24

• amyloid buildup occurs more than 10 years before symptom onset
• lots of people die with amyloid plaques in their brain but are still cognitively intact
• distribution of amyloid plaques are all over and don’t correlate with the symptoms of Alzheimer’s
• the amount of amyloid does not correlate with disease severity, a person with severe Alzheimer’s has the same amount of amyloid as a person with mild Alzheimer’s.

Question 25

Tell me about the Tau deposition hypothesis and what condition it’s for

Answer 25

Tau deposition is thought to be correlated with Alzheimer’s pathology. In neurons there are cytoskeletons made up of microtubules which helps transport nutrients and molecules across the cell, a special protein called tau makes sure these microtubules don’t break apart, it is spectaculed that a build up of beta amyloid outside the neuron triggers the activation of kinase which phosphorylates the tau protein causing it to no longer support the neuron and clump up together forming phosphorylated tau clumps or depositions inside the cell which can lead to diminished signaling and sometimes apoptosis

Question 26

Supporting evidence that tau deposition caused Alzheimer’s

Answer 26

• The deposition of tau correlates with the atrophy seen in patient with AD
• tau deposition correlates with symptoms of AD
• deposition starts in the medial temporal lobe where the hippocampus is located then to the temporal neocortex then parietal lobe then basal frontal lobe
• in those with AD, tau deposition gets worse / spreads more causing more damage so more tau = more damage

Question 27

Non supporting evidence for tau deposition

Answer 27

• Tau normally accumulates as you age (primary age related taupathy) which is usually asymptomatic
• The MAPT gene is what codes for the tau protein, when it is mutated you get frontotemporal dementia not AD

Question 28

What causes Lewy-body dementia

Answer 28

Caused by the accumulation of alpha-synuclein protein deposits inside neurons in the brain, it can present as dementia with Lewy-body or Parkinson’s disease dementia, Lewy bodies tend to build up in the cerebral cortex, substantia niagra, limbic system (emotional regulation) and the brain stem

Question 29

Why can Parkinson’s disease lead to Parkinson’s disease dementia

Answer 29

Parkinson’s disease can lead to mis-folding of alpha synuclein into lewy-bodies which disrupts neuronal function and leads to motor and cognitive symptoms such as visual hallucinations

Question 30

Differences between Lewy-body dementia and Alzheimer’s

Answer 30

LBD has fluctuations in cognition and visual hallucinations, LBD also has Parkinsonian features because the substantia niagra can be affected, memory impairment also comes in later stages

AD has progressive memory loss as it’s hallmark feature (first and most prominent feature), other cognitive domains are affected later, hallucinations are rare and have no Parkinsonian features or if they do then it’s in late stages. Cognition also declines steadily without significant fluctuations

Question 31

Explain how a muscle contracts starting at when a signal reaches the sarcoplasmic reticulum and ending when the myosin head binds to actin

Answer 31

(Side note: acetylcholine binding to nicotinic receptors cause Na+ flow into the muscle which activates the sarcoplasmic reticulum to release calcium)

It leads to a release of calcium which enter the sarcomas and into the myofibrils and sacromeres, calcium then binds to troponin which causes it to move a protein called tropomyosin which exposes the binding site on the actin filament for the myosin heads to bind to. Myosin head has ADP and a phosphate molecule, the myosin head releases phosphate which leads to myosin head binding to actin forming a actin-myosin cross bridge

Question 32

Explain how a muscle contracts starting at when myosin head binds to actin

Answer 32

After myosin releases its pi molecule and / or its ADP molecule the power stroke action occurs (the contraction). Once this happens a new ATP molecule will bind to the myosin head to bread the cross bridge and its dephosphorylation while cause the myosin head to be back to its cocked back position ready for the next contraction

Question 33

Changes to the zones and areas during contractions

Answer 33

A-band - (area shared between myosin and actin always stays the same) stays the same

I-band - (area of just actin) actin moves inward towards the myosin so I-band decreases

H-zone - (area with just myosin (H = hiding)) it decreases as more actin overlaps

Z-lines - (boundaries of sarcomere) it decreases as sacromere shortens

M-line - (midline) doesn’t change position

Question 34

Tell me what fine control and coarse control has in terms of motor units

Answer 34

Fine control = There are few muscles fibers per motor unit

Coarse control = there are many muscles fibers per motor unit

Question 35

What is oxidative capacity

Answer 35

How efficient the muscle is at producing energy via aerobic respiration

Question 36

Glycolytic capacity and tell me about type 2a fibres and what they’re known as

Answer 36

How efficient the muscle is at producing energy via glycolysis and anaerobic respiration

type 2a fibres have very high oxidative capacity, high glycolytic capacity (known as fast oxidative fibres

Question 37

What causes Myasthenia Gravis

Answer 37

An autoimmune condition where the immune system produces antibodies that block / damage acetylcholine receptors which prevents muscles from contracting, eye and facial muscles are commonly affected

Question 38

Acronym for Stance phase and what muscles are used

Answer 38

His Leg Might Halve

H - Heel strike (gluteus Maximus and tibialis anterior)
L - Loading (foot is flat) (Quadriceps)
M - Mid-stance (Gastrocnemius and soleus active)
H - Heel off ( aka terminal stance) (gastrocnemius and soleus)

Question 39

Acronym for swing phase and what muscles used

Answer 39

PIT

P - Preswing - (some may not consider it part of stance or swing phase) toes go off ground (rectus femoris)
I - Initial and mid swing (iliopsoas and rectus femoris)
T - terminal swing (hamstrings, tibilais anterior and ankle dorsiflexers involved)

Question 40

What is Rheumatoid arthritis and how does it present

Answer 40

Symmetrical polyarthritis of synovial joints with joint pain, swelling and stiffness affects small joints of the hands and feet especially the MCP, PIP and MTP (metatarsophalangeal) joints, it also can’t affect the spine or DIP joints but can affect shoulder, elbow, wrist and knee.

Question 41

What causes rheumatoid arthritis (Pre-synovial starting part)

Answer 41

Combination of environmental (cigarette smoke or pathogens) and genetic factors like susceptibility genes (known as HLA-DR1 and HLA-DR4). Type 2 collagen and vimentin can get modified through a process called citrullination in which the AA arginine is converted to the AA citrulline, because of HLA-DR1 and HLA-DR4 immune cells are sometimes not clever enough and get confuse by these changes and no longer recognize these proteins as self antigens

Question 42

What causes rheumatoid arthritis (Pre-synovial second part)

Answer 42

After the immune cells pick the citrullinated antigens they go to the lymph node to active CD4 t-helper cells which stimulate B-cells to start proliferating into plasma cells and produce specific autoantibodies which are anti-CCP (anti cyclic citrullinated peptide antibody) which targets citrullinated proteins), in rheumatoid arthritis these antibodies and T-cells enter the circulation and reach the joints.

Question 43

What causes rheumatoid arthritis (infiltration stage)

Answer 43

Macrophages enter the synovial join then release inflammatory cytokines like TNF-alpha, IL-1 beta and IL-6 (know that IL-1 beta is the main one that drives inflammation at the start), these cytokines stimulate the synovial cells to proliferate, the increase in synovial cells and immune cells creates a pannus which is a thick swollen synovial membrane with granulation tissue or scar tissues (made up of fibroblasts, myofibroblasts and inflammatory cells).

Question 44

What do synovial joints consist of

Answer 44

Fibrous joint capsule followed by synovial membrane which has cells that produce synovial fluid and articular cartilage

Question 45

What causes rheumatoid arthritis
(Damage stage)

Answer 45

Overtime the pannus can damage the cartilage, other soft tissue and erode bone. Activated synovial cells also secrete proteases which break down proteins in the articular cartilage and without this cartilage the bones rub directly against eachother. Inflammatory cytokines increase a protein in the surface of T-cells known as RANK-L, RANK-L allows the T-cells to bind RANK which is on osteoclasts and gets them to start breaking down bone. Meanwhile antibodies like rheumatoid factor which is an IgM AB that targets IgG AB. Another antibody is anti-CCP which targets citrullinated proteins, when these AB bind to their targets they create immune complexes which accumulate in the synovial fluid, there they activate the compliment system which further promotes join inflammation and injury. Finally the chronic inflammation causes angiogenesis which are new blood vessels around the joint which allows even more inflammatory cells to arrive. Synovial membrane cells can also migrate to other joins infecting them too

Question 46

Genetic mutations that cause familial Parkinson’s disease

Answer 46

SNCA which codes for alpha syunuclein
LRRK2 autosomal dominant
PARK2 linked to autosomal recessive inheritance

Question 47

What gene mutation causes ALS

Answer 47

SOD1 gene

Question 48

What gene codes for TAU

Answer 48

MAPT

Question 49

What is mutation of DISC1 gene increase risk of

Answer 49

Schizophrenia

Question 50

What do low-thiamine levels and alcohol withdrawal indicate

Answer 50

Alcohol-induced psychosis

Question 51

Symptoms of MS to do with eyes

Answer 51

MS can cause optic neuritis commonly in one eye which causes unilateral vision loss

Question 52

What causes Marcus Gunn

Answer 52

The trigeminal nerve controls movements of the jaw muscles (such as chewing or jaw opening).
The oculomotor nerve controls the levator palpebrae superioris muscle, which raises the upper eyelid.
In Marcus Gunn phenomenon, there is an aberrant connection between these nerves. When the trigeminal nerve is activated (e.g., during chewing, sucking, or jaw movement), it inadvertently stimulates the oculomotor nerve, causing the eyelid to move.

Question 53

How do inner hair cells work

Answer 53

When loud sound is heard olivocochlear bundle sends a signal causing the release of Ach to the inner hair cells leading to contractile proteins called presstin to contract dampening the sound by keeping by lowering inner hair cells

Question 54

How do inner hair cells work

Answer 54

When loud sound is heard olivocochlear bundle sends a signal causing the release of Ach to the inner hair cells leading to contractile proteins called presstin to contract dampening the sound by keeping by lowering inner hair cells

Question 55

What parasite can cause schizophrenia

Answer 55

Toxoplasma gondii