Final Exam Practice Questions Flashcards
Which cell type is particularly susceptible to damage during chemotherapy?
a) enteric neurons
b) interstitial cells of Cajal
c) enterocytes
d) commensal bacteria
e) vascular endothelium
c) enterocytes
Diarrhea results from…
a) dysfunctional internal anal sphincter
b) increased colonic water absorption
c) enhanced colonic segmentation activity
d) all of the above
e) none of the above
e) none of the above
Hepatitis leads to…
a) infection by 3 viruses
b) increased portal pressure
c) increased lipid absorption
d) increased colonic bile salt absorption
e) none of the above
b) increased portal pressure
Which of the following is not a symptom of Thiamine deficiency?
a) ST memory loss
b) weakness
c) heart failure
d) peripheral neuropathy
e) anemia
e) anemia
Which GI pathogen produces a toxin that indirectly stimulates the CFTR Cl- channel?
a) C. difficile
b) H. pylori
c) V. cholera
d) E. coli 0157
e) Fecalibacterium prausnitzii
c) V. cholera
Which mediators have been implicated in pain due to IBS?
a) acetylcholine and histamine
b) acetylcholine and serotonin
c) GLP-1 and serotonin
d) acetylcholine and microbial proteases
e) serotonin and histamine
e) serotonin and histamine
Blocking the actions of which mediator or signaling pathway would not be expected to reduce IBD severity?
a) TNF alpha
b) IL-23
c) TGF beta
d) alpha 4 beta 7 integrin
e) JAK
e) JAK
Case 1: John - 40yo teacher has burning sensation in chest’s center. Sometimes he gets a flood of bitter tasting fluid in his mouth that burns his throat. He was on proton pump inhibitors for a while and they helped, but now his symptoms are getting worse.
What might be the cause of these symptoms?
Gastroesophageal reflux disease with a possible gastric ulcer
What regulates lower esophageal sphincter tone?
- Myogenic tone e.g. its default state is contraction/closure, blocks food passage between stomach and esophagus except during a meal, belching or vomiting
- Reflux = loss of myogenic tone
What are the molecular targets of drugs that inhibit acid secretion?
- K+ H= ATPase (aka proton pump)
- Histamine reception - 2 antagonist
- Antacids provide temporary relief
What is a microbial cause of gastric ulceration? Describe how this microbe is thought to cause ulcers?
- Helicobacter pylori (distal stomach)
- Chemotaxis and flagellae - swims deeper into mucous and away from acid
- Urease - converts urea to CO2 + ammonia
- Evokes inflammatory response and release of gastrin, which causes acid secretion
What diseases present with diarrhea?
- Infectious disease
- IBD
- IBS
- Food sensitivities
Is weight loss more common among patients with IBS, IBD, or celiac disease?
IBD or celiac disease
What changes in motility and absorption/secretion cause diarrhea?
- Increased motility reduces time for fluid absorption
- Damage to mucosa leads to decreased fluid absorption
- Increased water and electrolyte secretion e.g. cholera
Describe the pain pathways from the gut? How are gut stimuli sensed?
- Sensory axons in gut lack specialized endings but can respond directly to changes in tension/inflammation - activated by release of enteroendocrine substances e.g. serotonin (pain relation)
- Subset of DRG neurons respond to noxious stimuli e.g. nociceptors
What are the causes of these 3 diseases: celiac disease, IBD, and IBS?
Are there differences in the parts of the GI tract affected? Are there systemic manifestations?
Celiac disease - small intestine
- Autoimmune inflammation following injection of BROW
- Systemic manifestations (rash)
IBD - any part of GI tract (mouth to anus)
- Autoimmune disease (not quite - more like chronic inflammation)
- Systemic manifestations
IBS - small and large intestines
- Functional disorder (no obvious tissue damage)
- Other pain syndromes, anxiety and depression (associations not necessarily result of IBS)
True of False? We have >800 billion cells in our brain
True
True or False? Brain messages travel as fast as 400km/hour
True
True or False? We only use 10% of our brain
False
True of False? Once we reach adult age, our brain’s structure does not change anymore
False
True or False? A spermaceti whale has the largest brain in the world
True
What is the main excitatory NT?
Glutamate
What is the main inhibitory NT?
GABA
What are the 3 types of pain?
- Cutaneous - shock, trauma, burn
- Somatic - tendon, muscle, joint
- Visceral - organs
What is allodynia?
Pain triggered by a stimulus that is normally painless e.g. sunburn
- Clinically important due to inability to do daily dask e.g. getting dressed
What is hyperalgesia?
Increased pain to painful stimulus e.g. hammer
What is the resting potential of neurons?
-60 to -80mV
What type of nerve fiber is the main nerve transmitting pain?
C (mechanical, thermal, and chemical pain) - non-myelinated (smallest diameter and slowest conduction speed)
What are the 3 main receptors of glutamate?
- AMPA receptor
- NMDA receptor - blocks MG pore so AMPA signals
- Metabotropic receptor (GPCR)
Afferent neuron - transfer info. orthodromic vs antidromic way?
In general afferent - ascending pathway = periphery to brain
Orthodromic - periphery to brain
Antidromic - brain to periphery
What does the term “sprout” mean?
Lamina III grow into Lamina II = pain sensation (consq. = touch perceived as painful)
What are the steps for neuro-immune interaction?
- Tissue damage (cut skin)
- Significant cell death (local)
- Immune cell influx
- Activation of immune cells
- Releases pro-inflamm mediators
- Activation and sensitization of sensory fibers
What is gate theory?
- Beta sensory fibers inhibit C fibers
- Massage sore area
E.g. phantom limb (touching does not change level of pain due to massive A-B fiber sprouting)
How is acupuncture related to this course?
- Stimulates A beta and A alpha fibers (activates inhibitory neuron in spinal cord like rubbing)
- Releases GABA (explains acute effect)
What is pain?
Not a stimulus but an experience - interpretation of the brain
*Expression of an unpleasant sensory and emotional experience involving existing or potential tissue damage
- # 1 MD consultation
- Acute = danger detection
- Can be chronic = pathology
- Precise location, emotion, and context dependent
What are the stages of pain transmission?
Transduction: Conversion of painful stimuli into electrical impulses by sensory receptors.
- Coding to be routed in poterior horn of spinal cord
Transmission: Conduction of these impulses along nerves to the spinal cord and brain.
- Marrow to thalamus
Modulation: Regulation of pain signals in the spinal cord and brain, either amplifying or dampening them.
- Plasticity - local and central sensitization/negative feedback pathway
Perception: Processing of the impulses in the brain, resulting in the conscious experience of pain.
- Brain - emotional component
What are pain receptors?
Also known as nociceptors - specalized sensory receptors detecting potentially harmful stimuli and transmit signals to brain, resulting in perception of pain.
E.g. ionoceptors (ion channels nociceptors) and GPCR (metabotropic nociceptors)
What’s the difference between NT and NP?
NT - small, fast synaptic transmission - rapid signaling
- Synthesized and stored in synaptic vesicles within the presynaptic neuron, released into the synaptic cleft, and bind to receptors on the postsynaptic neuron
NP - large (AA chains), slower signaling
- Synthesized as larger precursor molecules in the cell body, transported to the axon terminals, and released along with NT
What is neurogenic inflammation and an example of neuroimmune interaction?
Triggered by sensory nerve activation, leading to the release of neuropeptides and subsequent inflammation.
E.g. migraines - contributes to pain and other symptoms through vasodilation and immune cell recruitment
What is pain synapse plasticity?
Ability of synapses in NS involved in pain processing to undergo changes in structure and function.
- Signicant role in development and maintence of chronic pain by altering sensitivty pain pathways and contributing to amplification
What is a feedback mechanism - in the context of pain (central inhibition)?
- Body’s ability to regulate pain signals within CNS (when excessive or unecessary)
- Modulate or inhibit signals through a variety of mechanisms, e.g. releasing NT like endorphins or activating descending inhibitory pathways)
- Maintain homeostasis
What is the placebo effect? What is released during this process?
Taking medication or vehicle activates periaqueductal gray matter neuron
- Release glutamate to activate neurons
- Activates descending nerve fibers in spinal cord
- Release of opioid and adrenaline blocking neuronal activity
NOTE: Pts with more pain are more likely to respond to placebo effect
What is the stress paradox?
Very high stress situation - e.g. injured soldiers or athletes who do not feel pain for awhile
- Stress leads to activation of descending pain pathways
- Local opioid release in dorsal horn of spinal horn
- Activates pre- and postsynaptic mu (Gi/o) receptor
- AMP/c production block
- Decreased neuronal activation
What are the accessory digestive organs?
- Salivary glands
- Exocrine pancreas
- Liver (gall bladder)
List the parts of the small intestine from most to least distal.
Ileum, Jejunum, Duodenum
What does the esophagus connect?
Pharynx to stomach
Where do most gut cells arise?
Myenteric plexus
Difference between afferent and efferent neurons?
Afferent - sensory signals from intestine
Efferent - autonomic nervous system (parasymp and symp)
Difference betweem parasympathetic and sympathetic NS?
Parasymp - rest and digest (Para for peaceful process)
Symp - fight or flight (decreased BS)
What is the largest interface between the body and the outside world?
Mucosal surface
Where does the majority of absorption occur in the GI tract?
Small intestine
How are the liver and gall bladder realted to bile?
Liver - produces and secretes bile
Gall bladder - stores and concentrates bile - releases into duodenum in response to meal (x5 more concentrated here)
What is the motility of the GIT regulated by?
ENS and interstitial cells (in between other cells) of Cajal (all along gut)
What is segmentation?
Contraction of circular muscle in order to mix food without propelling food along GIT - SQUISHES (mix with enzymes during digestion)
What is peristalsis?
Corrdinated contraction of circular and lingutudinal muscle to propel food down GIT
What is the process of vomiting?
- Glottis closes
- LES relaxes
- Reverse perisatlatic waves
- Abdominal msucles contract
What happens during LES contraction and relaxation?
Contraction - Occurs after swallowing, prevent stomach acid and contents from flowing back up (reflux)
Relaxation - Occurs when swallowing food or liquids (allows to pass from esopahgus to stomach)
What is jaundice caused by?
Liver inflammation (dysfunction/damage) or gallbladder dysfunction
- High blood levels of bilirubin
What are the 2 functions of the pancreas?
- Exocrine secretion of enzymes and bicarbonate (food digestion)
- Endocrine secretion of insulin, glucagon, and somatostatin
What are the 4 main modalitites of the somatosensory system?
- Touch
- Propioception
- Thermal sensation
- Pain
What are the 2 main physiological roles of pain?
- Danger detection
- Avoid/escape (survival)
What is nociception versus pain?
N - Biochemical process allow you to detect danger - process info
P - perception/emotional experience of detection
What are the origins of chronic pain?
Idiopathic - no known cause
Inflammatory - tissue damage
Neuropathic - nerve damage
What does local cell death cause?
Activation of sensory neurons - immune cells
Give an example of cutaneous, somatic, and visceral pain.
C - cut or burn
S - sprain
V - heart attack
Give a few examples of inflammatory pain.
Stretching, twisting, bruising (back pain), arthritis, cancer, migraine
Give a few examples of neuropathic pain.
Post-herpetic neuralgia, diabetic neuropathy, phantom limb pain
- Nerve damge and immune cell influx
What do each of the following innervate: lumbar (DRG), inf. vagud nerve (ND), and trigeminals (TRG)
DRG - skin
ND - viscera and organs
TRG - face
What are ion channels sensitive to?
Heat, cold, chemical moelcules, amd pressure - can also detect bacteria
Is wasabi an example of TRPA1 (chemical) or TRPV1 (heat)?
TRPA1
What is the consequences of phosphoyrlating ion channels of sensory neruons?
Lower activation threshold - easier to activate and generate pain (RTK)
What are the non-painful receptors?
Mechanoreceptors
Thermoreceptors
Propioceptors
Where does the transmission stage of pain direct information to and from?
Periphery to brain (afferent)
List the transmisssion nerve fibres in order of largest/fastest to slowest/smallest.
A-alpha, A-beta, A-delta, C
What is another name for a neuropeptide?
Neuromodulator (activates GPCRs)
What is GABA’s precursor?
Glutamate
What are the signs and symptoms of inflammation?
pain, redness, heat, edema, loss of function
What are the 4 steps of the local response of neurogenic inflammation?
1) activation of sensory fibers (e.g. cut)
2) activates capillaries - vasodilation, increased BP
3) chemotacis of immune ceels (increased influx)
4) extravasation of immune cells near nerve endings
What are the 5 causes of central sensitization?
1) reduction in effectiveness of inhibitory synapses (GABA)
2) new synapses between A B fiber and C fiber - “sprout”
3) A B fiber de novo expresses inflammatory mediators
4) overexpression of new ion channels
5) genesis of ectopic discharge
What can you do to help stop allergic reactions?
- Block cyotkine receptor on nerve
- Block peptide receptor on T cells
- Block nerve
What does IL-10 always block?
Block inflammation - type of M2 microglia
List examples of M1 microglia that are pro-inflammatory.
IL-1 B, IL-6, TNF alpha
List some neuroendocrine effects.
Glucocorticoid - blocks immune cells
Catecholamine - hypertension
Decreased ghrelin - decreased appetitie
Decreased melatonin - difficulty sleeping
Decreased Insulin - glucose intolerance (diabetic)
What is the purpose of acute pain?
Warn the host - defend from danger (use reflex arc)
Why does chronic pain occur?
Chronic activation of nerve fibers - not supposed to happen (negative consequence)
Does active inflammation occur within IBD or IBS?
IBD
What type of NT is released in the LES?
- Major inhibitory (relaxatory) NT released in LES = nitric oxide gas
What senses are the nonpainful: mechanoreceptors, thermoreceptors, and propioceptors involved with?
Mechanoreceptors - touch, light pressure
Thermoreceptors - warm cold
Propioceptors - change in length and tension of muscles
Waking during night is common with IBS or IBD?
IBD
Is pain more often relieved after bowel movements for patients with IBS or IBD?
IBS
What is oily and undigested stool related to?
celiac/Crohn’s ileitis
What can a pain synapse plasticity occur in response to?
Various stimuli: injury, inflammation, chronic pain
Can you match dorsal horn and ventral horn with antidromic/orthodromic afferent neurons?
Orthodromic - periphery to brain (dorsal horn)
Antidromic - brain to periphery (ventral horn)
