Cell biology and pathophysiology

Question 1

Amyloid-B

Answer 1

aggregates in neurodegenerative disorders such as alzheimer’s
prevention of the peptide may be of benefit in mild cognitive impairment, but of limited use in later stages of alzheimer’s

CSF amyloid is reduced in alzheimer’s, possibly due to the increased buildup in the brain

Question 2

TAU protein

Answer 2

neurofibrillary tangles of tau protein
similar pathology to alzheimer’s
buildup in fronto-temporal lobes
leads to marked fronto-temporal lobar degeneration

Question 3

tau - phosphorylated

Answer 3

when excessively phosphorylated, there is reduced microtubule binding, and there is a promotion of aggregation
in normal health, when de-phosphorylated, tau protein remains bound to microtubules

Question 4

CSF - tau + AB

Answer 4

raised tau and reduced amyloid beta in the CSF is indicative of alzheimer’s

Question 5

substantia nigra

Answer 5

dopamine is oxidised and becomes melanin, which gives the substantia nigra its pigmented appearance
in parkinson’s, the substantia nigra will lose its darker tone due to the reduced dopamine, leading to reduced melanin

Question 6

alpha synuclein

Answer 6

leads to dementia with lewey bodies
much like tau, the aggregation seems to be driven by phosphorylation of the a-synuclein proteins
CSF levels also decrease

Question 7

spreading pathologies

Answer 7

transplanting alzheimer’s brain tissue into previously healthy brain tissue causes the disease to spread (in mice)

Question 8

pharmacological chaperones

Answer 8

act to help fold the proteins into an active conformation, which will allow them to function much closer to how they function in health
e.g. ivacaftor in for the CFTR channel protein in CF

Question 9

anaemia in childhood

Answer 9

impacts cognitive function in adulthood

Question 10

iron uptake

Answer 10

Fe3+ converted to Fe2+ before taken into the cells

Question 11

haemochromatosis

Answer 11

genetically inherited
autosomal recessive
seen in typically in males, and later in females due to menstruation
cirrhosis, hepatomas, diabetes, cardiomyopathy
iron deposits in the pituitary cause hypogonadotrophic hypogonadism. nothing wrong with the gonads
treated by removing blood, and therefore reducing the high iron

Question 12

haemochromatosis

Answer 12

genetically inherited
autosomal recessive
seen in typically in males, and later in females due to menstruation
cirrhosis, hepatomas, diabetes, cardiomyopathy
iron deposits in the pituitary cause hypogonadotrophic hypogonadism - no direct pathology in the gonads
treated by removing blood, and therefore reducing the high iron

Question 13

iron uptake

Answer 13

Fe3+ converted to Fe2+ before taken into the cells
high levels of iron downregulated ferroportin, causing iron to remain in duodenal endothelial cells, preventing it from over accumulating in the blood

Question 14

haemochromatosis

Answer 14

genetically inherited
autosomal recessive
seen in typically in males, and later in females due to menstruation
cirrhosis, hepatomas, diabetes, cardiomyopathy
iron deposits in the pituitary cause hypogonadotrophic hypogonadism - no direct pathology in the gonads
treated by removing blood, and therefore reducing the high iron

Question 15

copper metabolism

Answer 15

no inborn errors with no copper absorption - embryo lethal

Question 16

copper deficiency

Answer 16

fatigue
normocytic anaemia
peripheral neuropathy

zinc excess can lead to copper deficiency due to its reduction of copper absorption
often found in denture cream, and can then lead to copper deficiency

Question 17

copper deficiency

Answer 17

fatigue
normocytic anaemia
peripheral neuropathy

zinc excess can lead to copper deficiency due to its reduction of copper absorption
often found in denture cream, and can then lead to copper deficiency

copper also used in iron absorption so will cause iron deficiencies as well

Question 18

copper deficiency

Answer 18

fatigue
normocytic anaemia
peripheral neuropathy

zinc excess can lead to copper deficiency due to its reduction of copper absorption
often found in denture cream, and can then lead to copper deficiency

copper also used in iron absorption so will cause iron deficiencies as well

Question 19

copper toxicosis

Answer 19

acute vs chronic

Question 20

wilson’s disease

Answer 20

copper retention
ATP7B protein needed for copper storage
it is abnormal, or fails to be produced, so copper not stored, and overloads in the tissues

leads to cirrhosis, fatigue, extra pyramidal symptoms, cardiomyopathy, nephrocalcinosis

Question 21

menke’s disease

Answer 21

ATP7A
very similar to wilson’s but more severe
copper deficiency due to inability to uptake into the tissue