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ADVANCED PATHOPHYSIOLOGY Q&A.
Do women or men more often have multiple sclerosis? - Solution Women (2-3:1) Which disease has the following risk factors: -Epstein-barr virus (EBV) -Live above the 37th parallel -Caucasian -Female -Vitamin D deficiency: Decreased time between clinical isolated syndrome (CIS) and 2nd exacerbation -Smoking - Solution Multiple Sclerosis What is the main pathophysiological theory for multiple sclerosis? - Solution It's an autoimmune/neurodegenerative disease: -inflammation -demyelination/remyelination -permanent axonal damage What are the Myelin forming cells of the CNS? - Solution Oligodendrocytes What do T-Helper cell types 1 & 17 do? - Solution Pro-inflammatory What does T-Helper cell type 2 do? - Solution Anti-inflammatory What is the pathophysiology of Multple Sclerosis? - Solution 1. Autoreactive T cells express Very Late Antegen-4 (VLA-4, aka α4- integrin) on their cell surface and secrete Matrix Metalloproteinases (MMP).
- VLA-4 binds to Vascular Cell Adhesion Molecule (VCAM) receptors on the blood brain barrier (BBB) and MMP results in dysregulation of the BBB, allowing cell entry into the CNS.
- Once in the CNS, pro-inflammatory cytokines (TNF-α, INF-γ, and Osteopontin [OP]) are secreted resulting in inflammation and further T cell entry into the CNS.
- T cells in the CNS interact with microglia, astrocytes, and macrophages to produce reactive oxygen species and nitric oxide causing CNS damage.
- B cells acts as ACPs, enter the CNS, and produce myelin-specific antibodies that form membrane attack complexes with complement causing cell lysis. Which disease presents in the following way: **Visual changes, optic neuritis (Often the 1st sign/symptom) -Paresthesias -Gait issues/falls -Foot drop -Dysdiadochokinesia -Fatigue -Weakness -Impaired coordination -Cognitive changes MRI: ***Gadolinium enhanced lesions LUMBAR PUNCTURE TEST: -Increased IgG -Increased Myelin basic protein (MBP) -Increased CSF protein - Solution Multiple Sclerosis
-Decrease annualized relapse rate (ARR) -Slow progression of disease -Prevent/limit ADRs -Symptom management (fatigue, bladder dysfunction, cognitive dysfunction, constipation, depression) When monitoring MS patients should follow-up with their neurologists every _________. Get an MRI every ___________. - Solution When monitoring MS patients should follow-up with their neurologists every 6 months-1 year. Get an MRI every 1 year (based on need). What is the difference between seizure and epilepsy? - Solution Seizure: a discrete clinical event that results in the abnormal synchronous discharge of a set of neurons in the brain. Epilepsy: at least 2 unprovoked seizures occurring more than 24 hours apart. What is Status Epilepticus? - Solution Failure of the termination mechanisms for seizure leading to abnormally prolonged seizures. Length of seizure beyond 5 minutes and duration beyond the risk of long-term consequence (30 minutes). Which part of the brain is responsible for visual memory, organizing sensory information, emotional responses? - Solution Temporal lobe Which lobe of the brain is responsible for sensations (touch, feeling pain, spacial representation)? - Solution Parietal lobe Which part of the brain is responsible for planning, abstract thinking, organizing, reward system, pleasure? - Solution Frontal Lobe Which part of the brain is responsible for vision? - Solution Occipital lobe
Which part of the brain is responsible for voluntary movement (face, neck, trunk, upper/lower extremities)? - Solution Motor Cortex Which part of the brain is responsible for sensations of tingling, numbness, touch, smell of burnt rubber, parasthesisas? - Solution Somatosensory Cortex Which part of the brain is responsible for speech? and which part is responsible for speech terms of the formation of thoughts and word? - Solution Broca's: speech Wernicke's: formation of thought/words Which part of the brain is responsible for hearing? - Solution Auditory Cortex Which part of the brain is responsible for sensory information processing, perceptual disturbances? - Solution Association Cortex When does Epilepsy most often present in patients? - Solution Most often in infancy and childhood What are the International League Against Epilepsy (ILAE) Epilepsy etiologies? - Solution 1. Genetic
- Structural
- Infectious
- Metabolic
- Immune
- Unknown What is the pathophysiology of Seizures? - Solution 1. Excessive excitation of cortical neurons (hyperexcitable/hypersynchronization) -Abnormal functioning of Na/K pump, ligand-activated channels, voltage-gated channels. -Abnormal ATPase functioning -Abnormal synaptic vesicle protein 2-A
What type of seizure involves going from stiff to shaking, stiff to shaking? - Solution Tonic-Clonic Seizure What type of seizure involves no movement, and the patient just falls? - Solution Atonic Seizure If the seizure patient has dejavu what part of the brain is involved? - Solution Parietal or Temporal lobe If the seizure patient has sweating, salivating, pale skin, lip smack what part of the brain is involved? - Solution Autonomic area What type of seizure is caused by fever? - Solution Febrile Seizure What time frame is the best to get an EEG for a seizure patient? - Solution Within 4 hours of seizure When does Parkinson's onset usually occur? - Solution Over the age of 60 Do more men or women get Parkinson's? - Solution Men What are some of the etiology/Risk factors of Parkinson's Disease? - Solution -Idiopathic -Genetic predisposition -Environmental -Family History -Drug Induced Parkinsonism (DIP) What disease presents in the following way? -Tremor (slow, rhythmic, methodical, occurs at rest, initially unilateral, disappears with intention/sleep) -Rigidity (cogwheeling) -Bradykinesia -Postural Instability
-Shuffling gait -Small hand-writing -Smelling loss - Solution Parkinson's Disease What is the pathophysiology of Parkinson's Disease? - Solution -Injury to the dopaminergic pathway (Nirostriatial pathway: Substantia nigra to striatum) -Dopamine activity decreases (Dopamine inhibits the activity of acetylcholine) -Aceytlcholine activity increases -Nigral neurons cell death Which disease will most likely present with intraneuronal lewy bodies in the autopsy? - Solution Parkinson's Disease What effect does Dopamine have on the basal ganglia? - Solution Dopamine stimulates an inhibitory process, which has a dampening effect producing controlled muscle contraction. What is the differences in diagnoses (possible, probable, definite) for Parkinson's Disease? - Solution Possible: any one of the major symptoms (Asymmetric resting tremor, rigidity, bradykinesia) Probable: any two of the symptoms Definite: any two symptoms and responds to anti-parkinson's drugs For what disease might a DaTscan be done to diagnose the disease? - Solution Parkinson's disease What test is used to determine the severity of Parkinson's Disease symptoms? - Solution Hohen and Yahr Staging Which disease presents in the following way? -Bilateral tremor (involves the head)
In Dementia, does short-term memory or long-term memory loss come first? - Solution Short-term memory loss In Dementia patients which part of the brain has deficits? - Solution - Parietal lobe -Temporal lobe (specifically in the hippocampus) What are 3 physiological abnormalities involved with Dementia? - Solution 1. Neuronal loss
- Cell Death/Atrophy
- Ventricular enlargement In normal cognitive aging, there is a deficit in activity in the hippocampus and the patient becomes more dependent on what part of the brain? - Solution Entorrhinal cortex (takes over activity of receiving and output of information) What are the 6 cognitive domains? - Solution 1. Complex Attention
- Executive Function
- Learning and Memory
- Language
- Perceptual-Motor
- Social Cognition What is the difference between Major Neurocognitive Disorder and Mild Neurocognitive Disorder? - Solution Major Neurocognitive Disorder: -Evidence of SIGNIFICANT cognitive decline in 1 or more cognitive domains. -Interferes with independence. Mild Neurocognitive Disorder: -Evidence of MODEST cognitive decline in 1 or more cognitive domains. -Does not interfere with independence.
A patient with Major Neurocognitive Disorder is having difficulty with IADLs (housework, money management) what modifier of severity would be appropriate (Mild, Moderate, or Severe)? - Solution Mild, Major Neurocognitive Disorder A patient with Major Neurocogntivie Disorder is having difficulty with basic ADLs (feeding, dressing) what modifier of severity would be appropriate (Mild, Moderate, or Severe)? - Solution Moderate, Major Neurocognitive Disorder A patient with Major Neurocognitive Disorder is fully dependent, what modifier of severity would be appropriate (Mild, Moderate, or Severe)? - Solution Severe, Major Neurocognitive Disorder Which disease presents in the following way? -Cognitive dysfunction -Not age-dependent -Sudden onset -Typically reversible - Solution Delirium Which disease presents in the following way? -Cognitive dysfunction -Age-dependent -Slow and gradual cognitive decline - Solution Dementia What disease presents in the following way? -Aphasia (language impairment) -Apraxia (motor function imppairment) -Agnosia (failure to recognize) -Disturbed executive function -Delusions -Hallucinations -Depression -Sundowning
Which antibody is the principal mediator of Type 1 Hypersensitivity reactions? - Solution IgE In Type 1 Hypersensitivity reactions, what must a patient be exposed to?
- Solution An allergen In Type 1 Hypersensitivity reactions, what is the most important mediator? - Solution Histamine In Type 1 Hypersensitivity reactions, what is the principle effector cells, which release proinflammatory mediators? - Solution Mast cells In Type 1 Hypersensitivity reactions, what cell recruits eosinophils? - Solution T helper cells What cell is the primary cell responsible for inflammation? - Solution Eosinophil What cell is known as a "scavengers" which initiate the inflammatory cascade? - Solution Alveolar macrophage What type of Asthma is induced by exposure to an allergen, and develops within 10-20 minutes? - Solution Extrinsic (Atopic) Asthma What type of Asthma is non-allergic? - Solution Intrinsic Asthma In Extrinsic Asthma, what is the pathophysiolgic early-phase process? - Solution 1. Fast onset
- Antigen binds to IgE on Mast Cell
- Release of cytokines
- increased mucus/edema
- Bronchospasm
In Extrinsc Asthma, what is the pathophsyiolgic late-phase process? - Solution 1. Recruited cells (by cytokines) drive the response
- Airway epithelial cells also release eotaxin (which recruits eosinophils)
- Epithelial cell injury/bronchoconstiction
- increased airway responsiveness = prolonged asthma symptoms Which disease presents in the following ways? -Cough -Wheezing -Dyspnea/Chest tightness -Tachypnea & Tachycardia -Hypoxemia - Solution Asthma What disease presents in the following way? -Persistent respiratory symptoms -Airflow limitation that is due to airway and/or alveolar abnormalities -Onset later in life -Not fully reversible -Symptoms progessively worse -Neutrophils involved - Solution COPD What are some risk factors for COPD? - Solution 1. Smoking/second- hand (>90%)
- Occupational exposure
- Indoor air pollution
- Low birth weight/history of respiratory infections
- Heredity What are the inflammatory mediators for COPD? - Solution - Chemotactic factors (leukotriene B4 & Interleukin-8) -Cytokines (TNF-α & Interleukin-6) -Growth factors (TGF-β)
What is the Gold Classification of Severity Airflow for COPD for diagnosis in terms of the FEV1/FVC ratio (%)? - Solution <70% What two steps are involved in assessing COPD? - Solution 1. Gold Classification of Severity of Airflow
- Symptoms and Risk of Exacerbation What are the 3 cardinal symptoms of COPD exacerbations? - Solution
- Increased dyspnea
- Increased sputum purulence (change in color)
- Increased sputum volume What is "Staging" of COPD? - Solution Mild: 1 symptom Moderate: 2 symptoms Severe: all 3 symptoms Cardinal Symptoms of COPD:
- Increased dyspnea
- Increased sputum purulence (change in color)
- Increased sputum volume What are the complications of COPD? - Solution -Pulmonary hypertension -Persistent Hypoxemia -Cor Pulmonale (right side heart failure) -Polycythemia Vera (increased RBCs) -Increase risk of blood clots -Acute Respiratory Failure Which disease must have 2 or more of the following in a 1 month period of time & continual signs persist for at least 6 months:
- Delusions
- Hallucinations
- Disorganized speech
- Grossly disorganized
- Negative symptoms - Solution Schizophrenia *At least 1 sign must be 1, 2, or 3 Which disease must have 2 or more of the following in a 1 month period of time & continual signs persist less than 6 months:
- Delusions
- Hallucinations
- Disorganized speech
- Grossly disorganized
- Negative symptoms - Solution Schizophreniform Disorder *At least 1 sign must be 1, 2, or 3 Which disease must have 2 or more of the following for at least 1 day but less than 1 month:
- Delusions
- Hallucinations
- Disorganized speech
- Grossly disorganized
- Negative symptoms - Solution Brief Psychotic Disorder *At least 1 sign must be 1, 2, or 3 Which disease involves the presence of 1 or more delusions for 1 month or longer, criterion A for schizophrenia has not been met, functioning is not markedly impaired, behavior is not obviously bizzare? - Solution Delusional Disorder What are the Core Symptom clusters for Schizophrenia? - Solution - Positive symptoms (Delusions, Hallucinations, Disorganized speech, etc.) -Negative symptoms (Alogia, Avolition, Anhedonia, etc.) -Cognitive symptoms (memory, attention) -Mood symptoms (Dysphoria, Suicidality)
Decrease functioning of what pathway can lead to hyperactivity in the mesolimbic area? - Solution Cortico-brainstem pathway Does and NMDA antagonists increase or decrease serotonin levels in the prefrontal cortex? - Solution increases serotonin What are the 5 Neuropathological changes observed in Schizophrenia? - Solution 1. Neurotransmitters -Glutamate excitotoxicity (decreased GABA inhibition)
- Oxidative Stress
- Neurotrophins -decreased BDNF and NGF -decreased glial cells
- Molecular Cascades in Apoptosis
- Energy Metabolism -decreased mitochondria What is the difference between Bipolar I and II? - Solution Bipolar I involves manic episodes. Bipolar II does not. How long must symptoms last for a manic episode? - Solution at least 1 week How long must symptoms last for a hypomanic episode? - Solution at least 4 days How long must symptoms last for Cyclothymia? - Solution At least 2 years of hypomanic symptoms
What is Rapid Cycling? - Solution Four or more distinct mood episodes within a 12 month period. How long is the criteria for Major Depressive Episode to be diagnosed?
- Solution symptoms present during a 2 week period. What is the DIGFAST symptoms of hypomania and mania? - Solution D istractibility I nsomnia G randiosity F light of Ideas A ctivities S peech T houghtlessness How is Major Depression diagnosed? - Solution -At least 5 symptoms during the same 2-week period. At least 1 symptom either depressive mood or loss of interest/pleasure. -Significant distress or social impairment -Never had manic/hypomanic episode What is Persistent Depressive Disorder (Dysthymia)? - Solution - Depressed mood for most of the day/more days than not, for 2 years. -While depressed, presents 2 or more other symptoms (Insomnia, loss of appetite, fatigue, etc.) -Never been without symptoms for 2 months -Major Depression Disorder for 2 years. -Never had manic/hypomanic episode
