NURS 533 EXAM STUDY GUIDE ADV PATHOPHYSIOLOGY 2023 A+
ASSUARED SUCCESS
● Discuss the pathology and pathophysiology of Parkinson’s Disease, Huntington’s Disease, and
Alzheimer’s Disease.
o Parkinson’s Disease
■ Complex motor disorder accompanied by systemic nonmotor and neurologic symptoms
■ The main disease feature is degeneration of the basal ganglia (corpus striatum, globus
pallidus, subthalamic nucleus, and substantia nigra) involving the dopaminergic
nigrostriatal pathway
■ Pathophysiology:
The hallmark pathologic features of PD are loss of dopaminergic pigmented
neurons in the substantia nigra (SN) pars compacta with dopaminergic deficiency in
the putamen portion of the striatum
Dopamine loss in other brain areas including the brain stem, thalamus, and
cortex also occurs
Degeneration of the dopaminergic nigrostriatal pathway to the basal ganglia results
in underactivity of the direct motor pathway (normally facilitates movement) and
overactivity of the indirect motor loop (normally inhibits movement)
● This results in inhibition of the motor cortex manifested with bradykinesia
and rigidity
The subthalamic nucleus (STN) overactivity also influences the limbic
system, accounting for emotional signs and symptoms
Neuronal loss within the cerebral cortex is found in half of individuals with PD
Lewy bodies, fibrillar intracellular eosinophilic inclusions, and high concentrations
of alpha-synuclein, ubiquitin, tau protein, tuberculin, and other proteins are found
in the substania nigra, locus coeruleus, and other areas of the brain they are a
marker for neuronal degeneration
Molecular events thought to be associated with neurodegeneration of PD include:
● Mitochondrial dysfunction
● Oxidative stress
● Abnormal folding and accumulation of alpha-synuclein
,NURS 533 EXAM STUDY GUIDE ADV PATHOPHYSIOLOGY 2023 A+
ASSUARED SUCCESS
● Abnormal phosphorylation
● Dysfunction of the ubiquitin proteasome system (regulates
intracellular protein processing)
o Huntington’s Disease
■ Also known as chorea is a relatedly rare autosomal dominant disease with high penetrance
■ The onset of HD is usually between 25-45 years of age
■ Pathophysiology:
The genetic defect of HD is on the short arm of chromosome 4
● There is an abnormally long polyglutamine tract in the huntingtin (htt)
protein that is toxic to neurons and is cause by a cytosine-adenine-guanine
(CAG) trinucleotide repeat expansion (40 to 70 repeats instead of the normal
9-34)
● Age of onset is related to the length of the repeat sequences and
mechanism of toxicity
● Repeat lengths greater than 60 cause the juvenile form of the disease
The principle pathologic feature of HD is severe degeneration of the basal
ganglia (striatum), particularly the caudate and putamen nuclei and the frontal
cerebral cortex
● The degeneration of the basal ganglia leaves enlarged lateral ventricles
(box car ventricles)
Expression of the huntingtin gene produces tangles of protein that collect in the
brain cells and chains of glutamine on the abnormal molecules that adhere to each
other
The mechanism of neuronal death is unknown
The excitotoxic theory of striatal and cortical degeneration proposes that the
mutated huntingtin protein produces excitotoxic pathways mediated by glutamate
function that also induce concomitant dysregulation of dopaminergic function
The huntingtin protein also may alter mitochondrial function, which in turn
activates apoptotic pathways and causes neuronal death.
Neurotrophic factors also may be depleted, leading to loss of neurons
Basal ganglia and nigral depletion of GABA is the principle biochemical alteration
in HD
, NURS 533 EXAM STUDY GUIDE ADV PATHOPHYSIOLOGY 2023 A+
ASSUARED SUCCESS
Degeneration of the GABAergic pallidonigral pathway causes GABA depletion in the
substantia nigra with decreased inhibitory GABA activity on dopaminergic neurons
in the substania nigra and a relative excess of dopaminergic activity in the basal
ganglia feedback circuit within the cerebral cortex
● Manifested by hypotonia and hyperkinesia (involuntary,
fragmentary movements such as chorea)
Loss of excitatory glutamate may liberate the pathway from the thalamus to
the premotor cortex, impairing modulation of movement later in the course of
the disease
Producing energy for brain activity is difficult and there is a resultant buildup of
lactic acid
o Alzheimer’s Disease
■ Is the leading cause of dementia and one of the most common causes of severe
cognitive dysfunction in older adults
■ Nonhereditary, or sporadic, late-onset AD is the most prevalent form
■ Risk Factors:
The greatest risk factors are age and family history
Other risk factors: diabetes, midlife hypertension, hyperlipidemia, midlife obesity,
smoking, depression, cognitive inactivity, head trauma, elevated serum
homocysteine and cholesterol levels, oxidative stress, and neuroinflammation
■ Pathophysiology:
Early-onset familial AD (FAD) 10%
● Autosomal dominant and has been linked to three gene defects
o Amyloid precursor protein (APP) gene on chromosome 21
o Presenilin 1 (PSEN1) on chromosome 14
o Presenilin 2 (PSEN2) on chromosome 1
Late-onset AD 90%
● May be associated with chromosome 19 involved with Apolipoprotein E
gene allele 4
● Sporadic AD does not have a specific genetic association
ASSUARED SUCCESS
● Discuss the pathology and pathophysiology of Parkinson’s Disease, Huntington’s Disease, and
Alzheimer’s Disease.
o Parkinson’s Disease
■ Complex motor disorder accompanied by systemic nonmotor and neurologic symptoms
■ The main disease feature is degeneration of the basal ganglia (corpus striatum, globus
pallidus, subthalamic nucleus, and substantia nigra) involving the dopaminergic
nigrostriatal pathway
■ Pathophysiology:
The hallmark pathologic features of PD are loss of dopaminergic pigmented
neurons in the substantia nigra (SN) pars compacta with dopaminergic deficiency in
the putamen portion of the striatum
Dopamine loss in other brain areas including the brain stem, thalamus, and
cortex also occurs
Degeneration of the dopaminergic nigrostriatal pathway to the basal ganglia results
in underactivity of the direct motor pathway (normally facilitates movement) and
overactivity of the indirect motor loop (normally inhibits movement)
● This results in inhibition of the motor cortex manifested with bradykinesia
and rigidity
The subthalamic nucleus (STN) overactivity also influences the limbic
system, accounting for emotional signs and symptoms
Neuronal loss within the cerebral cortex is found in half of individuals with PD
Lewy bodies, fibrillar intracellular eosinophilic inclusions, and high concentrations
of alpha-synuclein, ubiquitin, tau protein, tuberculin, and other proteins are found
in the substania nigra, locus coeruleus, and other areas of the brain they are a
marker for neuronal degeneration
Molecular events thought to be associated with neurodegeneration of PD include:
● Mitochondrial dysfunction
● Oxidative stress
● Abnormal folding and accumulation of alpha-synuclein
,NURS 533 EXAM STUDY GUIDE ADV PATHOPHYSIOLOGY 2023 A+
ASSUARED SUCCESS
● Abnormal phosphorylation
● Dysfunction of the ubiquitin proteasome system (regulates
intracellular protein processing)
o Huntington’s Disease
■ Also known as chorea is a relatedly rare autosomal dominant disease with high penetrance
■ The onset of HD is usually between 25-45 years of age
■ Pathophysiology:
The genetic defect of HD is on the short arm of chromosome 4
● There is an abnormally long polyglutamine tract in the huntingtin (htt)
protein that is toxic to neurons and is cause by a cytosine-adenine-guanine
(CAG) trinucleotide repeat expansion (40 to 70 repeats instead of the normal
9-34)
● Age of onset is related to the length of the repeat sequences and
mechanism of toxicity
● Repeat lengths greater than 60 cause the juvenile form of the disease
The principle pathologic feature of HD is severe degeneration of the basal
ganglia (striatum), particularly the caudate and putamen nuclei and the frontal
cerebral cortex
● The degeneration of the basal ganglia leaves enlarged lateral ventricles
(box car ventricles)
Expression of the huntingtin gene produces tangles of protein that collect in the
brain cells and chains of glutamine on the abnormal molecules that adhere to each
other
The mechanism of neuronal death is unknown
The excitotoxic theory of striatal and cortical degeneration proposes that the
mutated huntingtin protein produces excitotoxic pathways mediated by glutamate
function that also induce concomitant dysregulation of dopaminergic function
The huntingtin protein also may alter mitochondrial function, which in turn
activates apoptotic pathways and causes neuronal death.
Neurotrophic factors also may be depleted, leading to loss of neurons
Basal ganglia and nigral depletion of GABA is the principle biochemical alteration
in HD
, NURS 533 EXAM STUDY GUIDE ADV PATHOPHYSIOLOGY 2023 A+
ASSUARED SUCCESS
Degeneration of the GABAergic pallidonigral pathway causes GABA depletion in the
substantia nigra with decreased inhibitory GABA activity on dopaminergic neurons
in the substania nigra and a relative excess of dopaminergic activity in the basal
ganglia feedback circuit within the cerebral cortex
● Manifested by hypotonia and hyperkinesia (involuntary,
fragmentary movements such as chorea)
Loss of excitatory glutamate may liberate the pathway from the thalamus to
the premotor cortex, impairing modulation of movement later in the course of
the disease
Producing energy for brain activity is difficult and there is a resultant buildup of
lactic acid
o Alzheimer’s Disease
■ Is the leading cause of dementia and one of the most common causes of severe
cognitive dysfunction in older adults
■ Nonhereditary, or sporadic, late-onset AD is the most prevalent form
■ Risk Factors:
The greatest risk factors are age and family history
Other risk factors: diabetes, midlife hypertension, hyperlipidemia, midlife obesity,
smoking, depression, cognitive inactivity, head trauma, elevated serum
homocysteine and cholesterol levels, oxidative stress, and neuroinflammation
■ Pathophysiology:
Early-onset familial AD (FAD) 10%
● Autosomal dominant and has been linked to three gene defects
o Amyloid precursor protein (APP) gene on chromosome 21
o Presenilin 1 (PSEN1) on chromosome 14
o Presenilin 2 (PSEN2) on chromosome 1
Late-onset AD 90%
● May be associated with chromosome 19 involved with Apolipoprotein E
gene allele 4
● Sporadic AD does not have a specific genetic association
