disease exampls (MS and diabetic neuropahty) Flashcards
(15 cards)
What does “lesions disseminated in space and time” mean in MS, and why is this physiologically important?
It refers to multiple demyelinating lesions affecting different CNS areas (space) at different times (time). Physiologically, this shows that MS is a progressive CNS autoimmune disease, where the immune system repeatedly targets myelin, disrupting neural signal transmission.
Explain how demyelination in MS impairs nerve conduction.
Myelin allows saltatory conduction by insulating axons and enabling fast signal jump between nodes of Ranvier. Loss of myelin in MS reduces conduction velocity, and if severe, blocks action potential propagation, impairing neural communication.
Describe the physiological mechanism underlying Uhthoff’s phenomenon in MS.
Heat increases ion channel activity. In demyelinated axons, altered sodium channels close prematurely and potassium channels leak, leading to hyperpolarization and action potential failure, worsening symptoms temporarily.
What is a clinically isolated syndrome (CIS), and how does it reflect the physiological process of MS?
CIS is the first episode of inflammatory demyelination, often caused by immune-mediated attack on CNS myelin, disrupting neural conduction. It physiologically mirrors MS but may not meet full diagnostic criteria without further episodes.
MS Urinary incontinence treatment Anticholinergics (e.g. Oxybutynin and botox)
Anticholinergics (e.g. Oxybutynin and botox)
block the actions of acetylcholine,
reduce detrusor excitation
=> reduced “urgency” (not contracting
as much) and improved ability to fill bladder
which block muscarinic receptors on detrusor muscle, reducing parasympathetic contraction.
MS Urinary incontinence treatment Beta-3 adrenergic receptor (AR) agonists (e.g. Mirabegron)
sympathetic,
increase detrusor relaxation
reduced “urgency” and improved
ability to fill bladder
MS Urinary incontinence treatment Alpha-sympathomimetics (or alpha AR agonists) (e.g. Midodrine)
increase internal urethral sphincter excitation è increases the
urethral resistance to urinary flow è improved bladder outlet
resistance (reduced “stress” incontinence)
How does physical therapy help physiologically manage MS-related symptoms like spasticity and weakness?
It improves motor neuron recruitment, muscle tone regulation, and synaptic plasticity. Stretching reduces hyperactive stretch reflexes that cause spasticity, while strength training enhances muscle function and coordination.
Relate lesion location in the CNS to specific physiological symptoms in MS. Provide an example.
Lesions in the spinal cord disrupt motor and sensory tracts, leading to spastic paresis or sensory loss. For instance, lesions in the corticospinal tract impair voluntary movement due to disrupted upper motor neuron signaling.
Contrast the pathophysiology of relapsing-remitting MS with primary progressive MS.
Relapsing-remitting MS involves intermittent immune attacks causing demyelination followed by partial remyelination, leading to fluctuating symptoms.
Primary progressive MS involves continuous low-grade inflammation and axonal loss, leading to steadily worsening function without recovery.
DAN: Pathogenesis
==>damages :
Peripheral autonomic nerves
Small blood vessels (vasa nervorum) that supply these nerves
Hyperglycaemia = high blood glucose (blood sugar)
Dyslipidaemia = abnormal blood lipids
Cascade of metabolic events triggered
by hyperglycaemia and dyslipidaemia
= eventually leading to =
*Increase in Reactive Oxygen Species (ROS) which leads to DNA damage and Endoplasmic Reticulum (ER) stress
*Inflammatory signals = inflammation (nerve conduction; vascular integrity
*Mitochondrial dysfunction = reduced ATP production, and more ROS (nerve resting potentials Na+/K+ ATPase)
*Apoptosis (cell death) = no neurons, ischemia (reduced blood supply to tissue)
DAN 🔹 PUPILS
Sign: Impaired pupillary adaptation to lowered light
Normally, parasympathetic nerves constrict the pupil (light reflex), and sympathetic nerves dilate it in darkness.
In DAN, autonomic nerve damage blunts these reflexes → the pupil doesn’t dilate well in low light → poor night vision.
DAN 🔹 GASTROINTESTINAL (GI TRACT)
GI motility is regulated by the enteric nervous system, which receives modulatory input from autonomic nerves (especially vagus nerve).
Damage leads to:
Poor esophageal peristalsis → difficulty swallowing
Gastroparesis = delayed stomach emptying → nausea, bloating, vomiting
Constipation/diarrhea due to dysregulated motility and secretion
Fecal incontinence = loss of sphincter control
DAN GENITOURINARY
Bladder and reproductive organs rely on precise coordination of sympathetic, parasympathetic, and somatic nerves.
DAN disrupts:
Bladder sensation and contraction → urinary retention or overflow incontinence
[( Parasympathetic nerves stimulate detrusor muscle contraction (to void).
Sympathetic nerves help relax detrusor and contract internal sphincter (to store).)]
Erectile dysfunction = loss of parasympathetic vasodilation [causes vasodilation of penile arteries → erection] and/or sympathetic pathways
Retrograde ejaculation = semen enters bladder due to internal sphincter failure
==> Normally, sympathetic nerves contract the internal urethral sphincter during ejaculation to prevent semen from entering the bladder.
In DAN, sympathetic failure = internal sphincter doesn’t close → semen flows backwards into the bladder.
Female dysfunction = impaired lubrication, arousal, or orgasm
==> Parasympathetic: mediates vaginal lubrication, clitoral engorgement (like male erection).
Sympathetic: controls orgasm and smooth muscle contractions.
🟰 Both parasympathetic and sympathetic
Dysfunction leads to impaired lubrication, arousal, reduced orgasmic response.
🩺 DAN: Current Treatment Landscape
🔴 No disease-modifying therapy (yet):
There’s no curative or reversing treatment for DAN.
Why? Because we haven’t yet found a specific target in the metabolic cascade (e.g., ROS, inflammation, mitochondrial failure) that can halt or reverse the nerve damage.
DAN is caused by chronic metabolic stress:
Hyperglycemia → ↑ ROS → mitochondrial damage, inflammation, apoptosis
Once the nerve or its blood supply (vasa nervorum) is damaged, it’s hard to regenerate.
So, the current approach is to prevent progression and manage symptoms.
✅ What Can Slow Progression?
✔️ Intensive Insulin Therapy
Shown in studies (e.g. DCCT trial for type 1 diabetes) to slow progression of DAN.
Works by:
Reducing blood glucose levels quickly
Limiting glucose toxicity
Therefore, lowering ROS, inflammation, and endothelial damage
🧠 Key point: The earlier and tighter the glucose control, the better the outcome for nerve health.
