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Pain is the body's
alarm system
Pain is classified by
-time (acute, subacute, chronic)
-etiology (malignant or non-malignant)
-mechanism (nociceptive or neuropathic)
-quality (fast (A-delta) or slow (C))
fast pain (A-delta) is
sharp, stabbing
Slow pain (C) is
aching, throbbing
pain can be broken up into
nociceptive or non-nociceptive
nociceptive can be broken into
somatic (surface, A-delta fast pain)
Visceral (deep tissue/organ, C slow pain)
non-nociceptive pain is
neuropathic
pain is generally a
protective, beneficial mechanism
pain is invoked by ____; alerts the individual to remove themselves from situation causing stimuli and damage
tissue damage
there are two types of pain with distinct sensations and distinct pain transmission pathways
Fast pain (via A-delta nerve fibers)
Slow pain (via C nerve fibers)
Describe fast pain
- rapid onset, within 0.1 second of stimulus
- intense; describes as sharp, stabbing, electric
- very well localized
- usually not felt in most deep tissues or viscera
describe slow pain
- beings 1 second or more after stimulus; builds
-burning, aching, throbbing or nauseous pain
- poorly localized, often diffuse pain
- usually associated with deep tissues and viscera
- tissue destruction and unbearable suffering
A-alpha fibers send impulses at a speed of
120 (100) m/sec
A-delta fibers send impulses at a speed of
10 m/sec
C fibers send impulses at a speed of
1 m/sec
slow pain can _______
wake you up
fast pain is conducted through the ___________ tract of the anterolateral spinothalamic pathway
neospinothalamic
Fast pain is primarily a mechanical stimulus that is transmitted through fast _____ fibers
A-delta
In fast pain, synapse in the dorsal horn of spinal cord with fibers that crossover and ascend up the anterolateral spinothalamic pathway in the neospinothalamic tract innervate the reticular formation and _____; some projections continue to the ____
thalamus, somatosensory cortex
fast pain Is _____ and graded in intensity ____ than slow pain
localized, better
Slow pain is conducted through the _____ tract of the anterolateral spinothalamic pathway
paleospinothalamic
slow pain is primarily through slow
C nerve fibers
Slow pain synapses in the dorsal horn of spinal cord with interneurons where they synapse and crossover to travel up the anterolateral spinothalamic pathway in the paleospinothalamic tract to the reticular formation (the ____ and ______ center); only 10-20% go to the thalamus
wakefulness, arousal
slow pain has very ___ localization and ____ (no projections to the somatosensory cortex)
poor, grading
Chromosomes are
DNA and proteins packaged tightly together
what are DNA and proteins packaged tightly together called
histones
What is the central dogma
how genetic information flows from DNA to proteins
describe DNA
-stable; long-term storage of information
-efficiently packaged
-accessible
describe mRNA
-unstable
-transient information intermediate
what is the template of genetic information
DNA
What is the product of genetic information
Protein
transcription is turning ____ into ____
DNA, mRNA
translation is turning ____ into ___
mRNA, protein
cytosine anneals to
guanine
adenine anneals to
thymine (DNA)
uracil (RNA)
nucleic acids have both a
sequence and a direction
DNA is ______ ____ strands
anti-parallel, complimentary
transcription occurs in the
nucleus
translation occurs in the
cytosol
a primary RNA transcript includes
exons and introns
a mature mRNA does not include
introns
_____ are removed from the RNA transcript
introns
Ribosomes read the bases of ______ and translate into
sequence, amino acid strand
the transcription regulation region
determines speed or if should transcription should stop depending on what binds
the promoter region is where
RNA polymerase binds to initiate transcription
a structural gene has both _______ (transcribed but not translated) and _____ (transcribed and translated)
introns, exons
what can regulate transcription rate
hormones, neurotransmitters, cytokines, growth factor, signal transduction products
specific proteins binding to DNA in the transcription regulation region can regulate the level of
specific transcription factors
peptide hormones, neurotransmitters, cytokines, and growth factor need ______ receptors
membrane-bound
steroid hormones, thyroid hormones, vitamin D3 etc need ______ receptors
intracellular
there are many levels of control for gene expression and protein activity. they are
transcription control, RNA splicing, mRNA transport, mRNA degradation control, Translation control, protein activity control
each of our diploid cells carry ______ of each gene, one from the mother and one from the father
two copies
the variants in the sequence of genes that vary slightly are called
alleles or polymorphisms
if both copies of a gene are the same allele, you are said to be ____ for that gene
homozygous
if you have two different alleles you are _____
heterozygous
SNP or single nucleotide polymorphisms may occur anywhere in the ______, the ______ and the _______
transcription regulatory region, promoter region, structural gene region
some SNP's cause
1. too much functional protein to be made (may cause disease)
2. too little functional protein to be made (may cause disease)
3. very little change in gene function (no disease)
alleles can impact either the ____ or ____ of a protein
quality, quantity
diagnosis and screening for susceptibility can be used for
- genetic diseases
- infectious diseases
- genetic susceptibility
what are the techniques used for diagnosis and screening for susceptibility
PCR, RFLP, DNA microchip arrays
genetic information can be used for treatment such as
1. utilization of recombinant DNA products (caries "vaccine")
2. antisense therapy
3. RNA/DNA vaccines
4. Gene therapy (ex vivo, in vivo)
What is diabetes mellitus
when plasma glucose is too high for too long; inappropriately elevated plasma glucose
What percentage of all US adults have diabetes mellitus
14.7%
The majority of type 2 diabetes is associated with
bodyweight control, diet, physical activity, genetics, stressors, systemic/oral health
What are some consequences of glycemic dysregulation and diabetes mellitus
periodontal disease, heart disease death rate, stroke, infections, blindness, renal failure, neuropathy, lower limb amputations, birth defects/miscarriages, pregnancy outcome, depression, overall health
The heart disease death rate is ______-_____ x higher with diabetes mellitus
2-4
the stroke risk is ____ -____ x higher with diabetes mellitus
2-4
Plasma glucose is regulated homeostatically to maintain a concentration of between ________ of plasma
70mg-100mg/100ml
what is hypoglycemia
low blood glucose
what can severe hypoglycemia lead to?
unconsciousness, brain and nerve damage, death
what is hyperglycemia
elevated blood glucose levels
what does hyperglycemia lead to?
formation of advanced glaciated end (AGE) products and disordered polyol metabolism which results in damage to blood vessels and tissues
what is glycemic control
plasma glucose homeostasis
what is insulin
functions to decrease plasma glucose when elevated
what is glucagon
functions to increase plasma glucose when its suppressed
What senses high glucose levels (what is the sensor)
pancreatic beta cells
Insulin is released from where
pancreatic beta cells
What are the effectors when glucose is high? (glucose is taken up by what?)
insulin sensitive cells
What senses low glucose levels (what is the sensor)
pancreatic alpha cells
Glucagon is released from where?
pancreatic alpha cells
what are the effectors when glucose is low?
hepatocytes
when glucagon binds to the hepatocytes (receptors on the liver), the glucagon undergoes _________ and________ before glucose is released into the ECF
glycogenolysis, gluconeogenesis
Plasma glucose is homeostatically controlled which means it is a ______ feedback loop
negative
What occurs following a meal
1. carbs digested and glucose enters bloodstream
2. blood glucose increases and taken up by beta cells
3. insulin released into blood stream
4. insulin binds to receptors
5. insulin signals to take in glucose by bringing GLUT4 to surface
6. Glucose enters cells via GLUT4, blood glucose decreases
Insulin receptors are found on insulin sensitive cells that are primarily ______ and _____ cells
skeletal muscle, fat
When blood glucose is high, insulin also strongly inhibits the release of _____ from the liver and the release of _____
glucose, glucagon
When insulin binds to an insulin receptor, insulin signals GLUT4 to translocate from the _____ to the ______
Golgi, cell membrane
plasma glucose enters cell moving _____ its chemical gradient
down
Glucose is not the only regulator of insulin in healthy people. Food in the GI tract signals the release of _______ hormones
incretin
glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP-1) stimulate ______ release and inhibit ______ release which is known as the ________ _____
insulin, glucagon, incretin effect
During exercise, insulin release is _______
inhibited
What occurs during a period of hypoglycemia in a healthy person
- insulin secretion decreases due to low glucose, GIP, and GLP-1
- glucagon is released primarily due to low insulin and low glucose
- Glucagon stimulates the release of liver glucose to help restore blood glucose level
Following a meal, there is a normal period of hyperglycemia that is corrected by the
increased release of insulin
following a fast, a drop in blood glucose will be corrected by the
increased release of glucagon
if blood glucose is too high for too long what occurs
gradual but progressive damage to blood vessels and tissues; severity dependent on duration and degree of hyperglycemia
How fast does hyperglycemic damage occur
occurs over years
if blood glucose is too low for too long what happens (70-50 mg/ml)
shakiness, dizziness, nauseated, sweaty, irritable, weakness, nervousness, headache
if blood glucose is too low for too long what happens (
neural dysfunction, loss of consciousness, seizure, coma, death
How fast does hypoglycemic damage occur
within minutes
How are type I and II DM different
differentiated by the mechanism leading to hyperglycemia, treatment and specific concerns