Biol 1080 Flashcards
(139 cards)
1
Q
Systems Biology
A
Interactions and dynamics within the biological system. Complexity.
- all levels genes, prots, organs, systems
2
Q
Emergent Properties
A
- a property of a system that is not necessarily evident from the individual components.
3
Q
Reduction vs. Integration
A
Reduction:
- isolated
- lots of control over conditions
- makes the mechanism clear
e.g acute diseases: UTI, appendicitis, aortic aneurysm
Integration:
- less control
- less mechanistic (most important factor)
- Real-world
e.g complex diseases: diabetes, asthma, coronary artery disease
4
Q
Biological Concepts of Health
A
1) each human can be considered a unique BS (emergent properties)
2) The BS has a CCN that coordinates function:
- CNS
- PNS
- Endocrine S
- Support and Defense
3) CCN controls and processes info flow
- always on
controls and coordinates all systems including itself
- throughout entire body
- each component has multiple functions
- communication via chemical cell-to-cell communication (everything is connected)
4) CCN is the focal point of health
- inputs: genetics, environment, lifestyle
- outputs: to 7 dimensions of health
5) Aging and disease represent the compromised function of the CCN
6) SB integrated approach to health will enhance medical healthcare practice
- P4, personalized, predictive, preventative, participatory
5
Q
In Silico
A
Mathematical and computer modeling to create simulations.
6
Q
In Vitro/Ex Vivo
A
“In Glass”
- cell cultures
- growing skin
“outside living”
- isolated organs
- isolated cancer cells
7
Q
Animal Models
A
Elegans: 40%
- easy and cheap
- self fertilizes
- can be frozen and thawed
- transparent
Fruit Flies: 65%
- sensitive to environmental conditions
Rats:
- social and intelligent
- lifestyle effects on metabolism
- more severe approach
- not a good model for infants
- some genetically modified rats
Mice:
- easy to apply recombinant DNA tech
- can test the importance of a single protein (compensatory mechanisms)
- lifestyle affects on metabolism
Swine:
- piglets, best primate model for infant development and metabolism
- organ transplants (xenografts)
Primates:
- closest to humans
- Ethics? cost?
8
Q
Mice vs. Rats
A
- takes longer to make a mouse insulin-resistant
- muscle metabolism differs
- less impairment of glucose
uptake in mice with high-fat
diets - mitochondria adapt less
with exercise training
- less impairment of glucose
9
Q
Non-clinical studies
A
- no treatment given
- cannot predict “cause and effect” more “association and correlation”
- epidemiology studies
10
Q
Clinical studies
A
- treatment or placebo given
- “cause and effect”
- double blind placebo- controlled
11
Q
Stages of Clinical Trials
A
1) preclinical - animal studies/in silico
2) Phase 1 - is the drug safe (small group)
3) Phase 2 - Is it effective (100s) - dosage, safety
4) Phase 3 - how does the drug compare (1000s)
5) After approval - assessment of long-term use
12
Q
Cochrane Collaboration
A
Database of systematic reviews and meta-analyses which summarize and interpret the results of medical reviews
Pyramid:
- Info begins: animal testing, in silico, in vitro
- Non-intervention cohorts and case studies
- Blinded controlled interventions
- Info end: less available but more relevant critically acclaimed papers and topics and systematic reviews.
13
Q
Evolutionary Medicine
A
Applications of evolutionary theory to understanding health and disease
- is fight or flight always on?
- is our modern diet healthy?
- is little exercise a signal were injured - turn on inflammatory response and slow metabolism
14
Q
Integrative Medicine
A
- healing oriented
- Takes account of the entire person
- mind, body, soul
- uses all appropriate therapies
15
Q
Collective Medicine
A
- improve health of all species
- collaboration and cooperation btw all medical and science professionals
16
Q
Enhancement medicine
A
- Botox
- Viagra
- liposuction
- nootropics (brain enhancers) - omega 3 fatty acids
17
Q
Lifespan Vs. Health span
A
Life: how long do I have to live?
Health: how long can I live a healthy independent life?
18
Q
Biomarkers
A
- can measure objectively to track aging and disease
- indicators of the biological state
Must: - reflect normal function or disease/predict development
- predictable range or routinely monitored
- have accurate and precise measurements
19
Q
Height as a Biomarker
A
- decline begins around age 40
- disk degeneration/ compression
- bone degeneration
- likely to get compression fractures
- kyphosis (curving of the spine due to osteoporosis)
- if the decline is outside the normal range it is an indicator of poor health
- height varies daily (about 2cm)
Limitations: - varies daily
- must be measured over time
- not very sensitive to disease
- doesn’t directly predict the disease state
20
Q
Muscle Mass as an Indicator
A
- up to 1% after age 40
- Male: decrease in testosterone, IGF-1, and inactivity
- Females: inactivity, estrogen
Prevent: - strength training 2-3x per week
- eating protein
21
Q
New era of Biomarkers
A
1) networks within organs are perturbed during disease states
2) panels of blood markers (prots, RNA, metabolites) provide assessment of perturbed networks and organs
22
Q
Chronobiology
A
Ultradian (less than 24 hrs)
- appetite ghrelin, cortisol
Circadian (24 hours)
- cortisol (sleeping: peaks at 8am)
Infradian (more than 24 hrs)
- menstrual cycle
23
Q
Circadian/Diurnal Rhythms
A
- controlled by a peripheral “clock” controlled by a “master clock”
- controls gene expression and enzyme activity (hormones, neural function)
- coordinate sleep, nutrient supply, activity patterns (metabolic)
Disruption:
- elevated inflammatory cytokines
- GI function
- Obesity, diabetes, cardiovascular complications
- Metabolic syndrome
- heart attacks
- cancer
- Alzheimer’s disease
- night owls suffer more mental stress
24
Q
Master Clock
A
- suprachiasmatic nucleus (brain region, time-based off light signals
- The peripheral clock coordinates metabolism with the rest of the body
Control: - light-dark cycles (still in blind individual)
- probably melatonin (pineal gland)
- blue spectrum light inhibits melatonin release
25
DEXA (dual-energy X-ray absorptiometry
- determines bone mineral density
- estimates the amount of absorption of dense hydroxyapatite in the extracellular space (collagen) of the bones (the denser the bone the more x-ray blockage)
26
Bone and Plasma Ca2+ Homeostasis
Intestine - Net Ca absorption
Kidney - Net Ca excretion
Bone - Net Ca deposition
All regulate with the plasma
PTH - prevents a decrease in plasma Ca2+ (adding)
Calcitonin - Prevents an increase in plasma Ca2+ (taking)
27
Osteoporosis
Main Fracture Sites:
- neck of femur (hip bone)
- intervertebral disks (back and neck)
Age-related:
- Diff in men and women
- peak bone density at 20-30
- increased degeneration with menopause
Scale:
1T - better than fine
0T - fine
-1T - 2X
-2T - 4X
-3T - 8X
-4T - 16X
Max Bone Density:
- consume calcium in childhood
- get vit D
- Weight-bearing physical activity/constant exercise
- stable BMI
- get sleep
Hinder:
- smoking, alcohol, caffeine
- high phosphate
- drugs (corticosteroids)
28
Intercellular Communication
1) Direct Communication
- gap junctions
- membrane nanotubes
- mechanosignals
2) Indirect Communication
- chemical messengers
29
Direct Intercellular Communication
a) Gap junctions:
- connexons - subunits forming a channel
- small pore size (sugars, aa, ions)
- all cells except mature skeletal
cells
- intercalated disks - rapid coordination and
propagation of action
potentials (muscle
contractions)
- smaller than connexons
- acutely regulated via
phosphorylation
b) Membrane Nanotubes - formed by PM
- longer and larger pore
- transfer nucleic acid and
small organelles (apoptosis)
c) Mechanosignal Transduction - mechanical
(physical) stimuli into cell response
30
Indirect Intercellular Communication
a) chemical messengers
- paracrine (btw cells locally) - clotting factors and growth factors, bind to receptor
- neurotransmitter - synapse, tightly controlled, auto shutoff (reuptake)
- hormones - travel through bloodstream
*receptor specificity - control, 100 to 100a of receptors on a cell (amplification)
31
Hydrophilic messengers/hormones
Water-soluble
- water-loving
- aa, amines, peptides
- must be transported out of the cell (exocytosis)
- STORED inside the secretory cell
- dissolves in plasma - no carrier
- binds to PM receptor
- directly or via messengers alters activity of EXISTING enzymes and proteins
- signal transduction mechanism: ion channels, second messenger
Response time: fast
Duration: short
Half-life: short
ex. insulin, epinephrine, serotonin
32
Hydrophobic messengers/hormones
Lipid-soluble
- water-hating/lipid-loving
- steroids, thyroid hormones
- limited storage (made on demand)
- cannot dissolve in plasma - needs a carrier
- no problem crossing barriers
- binds inside the cell (cytosol or nuclear receptor)
- turns on genes to make NEW proteins
- Signal Transduction: altering mRNA
Response time: slow
Duration: long
Half-life: slow
ex. sex hormones (estrogen, testosterone, cortisol)
33
Amplification (where does it occur)
Lipid-soluble:
- one hormone/receptor complex causes many mRNA to be formed
- many proteins formed from each mRNA
Water-soluble:
- adenyl cyclase generated 100's of cAMP molecules
- each protein kinase A phosphorylates 100's of proteins
34
Signal Transduction
Lipid-soluble:
- into cell
- binds to a nuclear receptor
- this complex alters mRNA
- mRNA travels outside of the cell
- mRNA initiates protein synthesis (translation)
Water-soluble: (G-protein example)
- binds to PM receptor
- G-proteins activated
- G-protein activates adenyl cyclase
- AC generates cAMP molecules
- cAMP activates proteins kinase A
- PKA phosphorylates hundreds of proteins
35
Neuroendocrine system
- Neuron secretes neurotransmitter/hormone (N)
- travels through bloodstream (E)
- Targets receptor on endocrine cell (E)
Delayed onset
Longer effect
36
Nervous vs. Endocrine
Nervous:
- neuron
- target neuron, muscle, or gland
- neurotransmitter
- across synapse
- receptor on postsynaptic target
- immediate response
- brief duration
Endocrine:
- endocrine cell
- targets most body cells
- hormone
- via bloodstream
- receptors on target body cells
- delayed onset
- longer duration
37
Central NS
Sensory input
CNS: brain and spinal cord
motor output
Either Somatic or Autonomic NS
Somatic:
- voluntary (acetylcholine)
Autonomic:
- involuntary
From autonomic to parasympathetic or sympathetic NS
Parasympathetic:
- restful conditions (acetylcholine)
Sympathetic:
- non-restful (norepinephrine)
38
Major Cell types in CNS
1) neurons
2) oligodendrocytes and Shwann cells
3) astrocytes
4) microglia
5) ependymal cells
2-5 are glial or non neuronal
39
Neurons
Built for:
- information flow
- speed (myelination)
- signaling specific cells with specific neurotransmitters (1 neurotransmitter for each presynaptic neuron)
- excitatory or inhibitory (effect is the sum of all inputs) - on or off
- diverge, converge, and network
* beginning age 10 the brain remodels its neural network
- new synapses
- pruning old ones
Teenage brain: reorganization and development of synapses
- increased dopamine sensitivity
- increase in myelination
40
Oligodendrocytes and Schwann Cells
Oligodendrocytes:
- CNS
- span multiple axons
- support 30 myelin rolls
Schwann Cells
- PNS
- do not span multiple axons
41
Astrocytes
- more abundant than neurons
- star like
Functions:
- coordinate the function of BBB and provide nutrients to feed neurons
- coordinate function of ventricle epithelial (heart)
- coordinate the function of notes of Ranvier (gaps in myelin)
- form tripartite synapses with neurons
- superhubs for neural networks (syncytium formation) and calcium signaling (astrocyte clouds)
42
Microglia
Mobile macrophage-like immune cells
- small and thin
43
Ependymal Cells
- line ventricles to form a barrier
- produces cerebral spinal fluid
44
Blood Brain Barrier
- tight control over what gets through to the brain
- protect against bacteria and toxins
What gets through?
- fatty acids
- caffeine and alcohol
- glucose (GLUT1 transporter)
*some drugs are a challenge associated with the BBB
45
Brain Imaging Technics
Function MRI (fMRI) - tracks blood flow (deoxyhemoglobin is paramagnetic)
PET - tracks glucose uptake (glucose tracer)
46
Neurotransmitter Networks
- neurons using the same neurotransmitter
eg. norepinephrine, serotonin, acetylcholine, dopamine
47
Norepinephrine Network
- attention
- sleep-wake
- learning
- memory
Psychostimulants:
- methamphetamine
- Ritalin (ADHD - "smart drugs")
- caffeine
48
Serotonin Network
- pain
- sleep-wake
- emotion
Antidepressants increase serotonin
- low serotonin - migraines
49
Acetylcholine
- arousal
- sleep-wake
- learning
- memory
- sensory info
Alzheimer's:
- massive loss of cholinergic neurons
- low acetylcholine levels
Drugs to treat Alzheimer's: cholinesterase inhibitors - cholinesterase breaks down acetylcholine
50
Dopamine Network
- motor control
- reward/ pleasure centers
Advanced Parkinson's: loss of dopamine network
- dopamine agonists increase health-span of Parkinson's
- too much meds causes hypersexuality and impulse control issues
51
Dopamine and Drugs
- addictive drugs like cocaine block dopamine reuptake
- dopamine increased by natural endorphins (exercise and food)
GABBA inhibits dopamine response
cocaine: blocks reuptake
heroin and morphine: block GABBA release
52
Role of Hormones
- growth and development
- homeostasis
- reproduction
- neurodevelopment
- immunity
53
Endocrine Glands
- pituitary glands (specifically AP)
- pineal glands (melatonin)
- thyroid (TH, calcitonin)
- adrenal (estrogen, cortisol, androgen)
- parathyroid (PTH - calcium)
Adipose tissue (fat), skeletal muscle both produce hormones
54
Target Organ
- pancreas (insulin)
- sex organs (estrogen, progesterone, androgen)
- GI system
55
NS to ES
1) nerves release NT into the blood
2) prim and secondary endocrine tissues are innervated (have nerves in them) by neurons
- NT regulates hormone secretion
e.g norepinephrine causes increased epinephrine and decreased insulin
3) Neurons in CNS and PNS have receptors for hormones
56
Posterior Pituitary Gland
- technically not a gland because does not produce hormones
- collection of nerve endings
- made in the hypothalamus
- travels via the bloodstream to PP
- released via PP
Oxytocin:
- uterine contraction
- milk ejection
- love/bonding
ADH:
- retains fluid in kidney
* made on demand
57
Anterior Pituitary
- true gland
- secretes many hormones: prolactin, ThyroidSH, AdrenocorticotrophicH, GH, LH, FSH
- Initial hormones come from the hypothalamus into the bloodstream
- causes AP to release hormones which target certain organs
*review the table of movement of multiple hormones
58
Growth Hormone
Hypothalamus - GHRH
AP - GH
Organs - liver, bone, muscle, adipose
- increased IGF-1 release - leads to anabolic affects and storage of growth factor
Bone - can still grow in adulthood (nose and brow)
Muscle - does not respond to GF in adulthood as much
Adipose - signaled by a growth factor causes lipolysis, breaking down fat
Taking GH as an adult:
- increased bone growth
e.g face and shoe size
59
Effects of Steroid Use
- brain cancer
- depression
- deeper voice
- yellow eyes and skin
- severe acne
- stunted growth
- weaker tendons
- effects on breasts (dec in women inc in men)
- irregular menstrual cycles
60
Why are steroids dangerous?
1) taking way too high a dose
2) dosing yourself doesn't follow circadian rhythm (harmful)
61
Role of the Support and defense System
- immune response
- maintenance
- repair
- removal of cells
- patrols for the appearance of transformed cell populations (cancer)
62
Innate/Non specific defenses
First Line of Defense:
- Chem barriers (secretions)
- Physical Barriers (skin)
Second Line of Defense:
- Cells
- Proteins
- Inflammation
- Fever
63
Adaptive immune system/specific defenses
Third Line of Defense:
- immune response
e.g T-cells, B-cells, antibody responses
64
First Line of Defense
Chem/secretions
- Tears (kills bacteria, washes away microbes)
- Saliva (washes away microbes)
Barriers: (Phys/chem)
- Skin (slightly acidic - no bacteria)
- Respiratory tract (mucus - traps, cilia - sweep away trapped organisms)
- Stomach (acidic - kills orgs)
- Large intestine (gut microbiota - kills invaders)
- bladder (urine washes microbes from urethra)
65
Second Line of Defense
*identifies foreign matter but has no memory
- Cells - kills invaders - bacteria, organisms
- Proteins - kill invaders - viruses. etc
- Inflammation - widening of blood vessels (increased blood flow - nutrients, cells, proteins), speeds healing
- Fever - slows bacteria growth, immune system works better under higher temps
66
SLofD - Cells
Phagocytic:
- macrophages (engulf anything/bacteria)
- neutrophils (first on-site, specifically bacteria)
Non-phagocytic: target pathogens/organisms
- natural killer cells (attack cancer)
- circulate and patrol
- release perforin and proteases to destroy
cell (breaks so it explodes)
- eosinophils (discharge digestive enzymes)
67
SLofD - Protein Defense
Complement System
- 20+ proteins synthesized in liver
- released inactive
- activated by contact with foreign material
(e.g sugars/polysaccharides, antigen/antibody complex - adaptive immune system)
- enhances phagocytic cells and antibodies to clear microbes and damaged cells
- promotes inflammation and attacks pathogen cell membrane
1) punches holes in bacteria
2) bacteria can't maintain their environment
3) bursts + destroys cell
68
SLofD - Inflammatory Response
- histamine released from mast cells
Effects like:
Redness - increased blood flow
Heat - increased metabolic rate
Swelling - increased blood flow
Pain - slows movement to allow repair
RICE - rest, ice, compression, elevate
Inflammation response to Tissue damage/stress
- bruises and torn tissue (acute)
- obesity, arthritis, disease (chronic)
*obesity can lead to other issues
69
SLofD - Fever
*not always caused by infection - could be caused by underlying conditions like cancer, drug reactions, endocrine disorders, chemotherapy
- Infection
- immune cells produce pyrogenic cytokines
- they target the hypothalamus to produce cAMP
- cAMP elevates the body temp
- produces fever
70
Parenchymal Cells - examples
Functional cells (secretion)
- usually the most prominent cell type in a tissue, organ, or gland
e.g
- heart - cardiomyocyte
- brain - neurons
- liver - hepatocytes
- muscles - myocytes
- pancreas - various secretory cells, aplha cells ,beta cells, F cells, delta cells, exocrine pancreus
71
Stromal Cells - examples
Support cells (support, communication, defense)
- supports parenchymal cells
- forms LSDS
e.g
- neurons - control func of almost all cells/tissues
- astrocytes - BBB, supports neural network
- stem cells - divide and replace parenchymal cells
- Gap Junctions - communication btw parenchymal cells
72
Third Line of Defense
- specific defenses
- adaptive immune system
73
MHC (Major Histocompatibility Complex)
- located on macrophages
- the surface of the cell
- both self and non-self antigens are displayed
74
Process of Attack
1) Threat - invader enters
2) Detection - macrophage finds and engulfs invader
3) Alert - macrophage takes antigen and presents it to helper T-cell and secretes an enzyme to activate T-cell
4) T-cell responds to a recognition and verification signal
5) Helped T cell divides into either an effector helper T-cell or memory helper T-cell (continued surveillance)
6) Effector helper T-cells activate either naive B cells, or naive cytotoxic T cells
75
B-Cell route of attack
Antibody-mediated attack
ANTIGENS!
1) naive B cell activated
2) cell divides into either memory B cells or effector cytotoxic B cells
3) effector cytotoxic B cells/plasma cells secrete antibodies
4) antibodies target specific pathogens or toxins outside of the cells (attract macrophaes, trigger release of complement)
antibodies bind to antigens to initiate specific events
76
T-Cell route of attack
1) Naive T-cells activated
2) naive t-cells divide to produce memory t-cells or effector cytotoxic t-cells
3) effector cytotoxic t-cells target cells infected with an intracellular pathogen like cancer or organ transplant cells
* attacks via chemical; means (perforins)
77
Antibodies
- neutralize foreign proteins
- trigger release of complement
- attract more macrophages
*B-cells do NOT engage
- antibodies bind to specific antigens to initiate the above events
78
Antigen
- a protein on the surface of a pathogen like bacteria
- helps identify a 'foe'
79
Components of the Cardiovascular System
- Heart - muscular pump
- blood vessels - transport nutrients
- blood - holds materials to deliver
- lymph and lymph vessels - carry nutrients and WBC through the body
- CSF and CSF vessels - nutrients
- extracellular fluid
- Kidney - erythropoietin, filtering
- spleen, thymus, tonsils - hold immune cells and blood
- lungs - O2 and CO2 exchange
- bone marrow - stem cell pool
80
Travel of blood around body
- Deoxygenated blood travels into the right atrium via veins through the venae cavae
- This blood gets pumped into the right ventricle through the tricuspid valve
- The blood then gets pushed out the right ventricle through the pulmonary valve into the pulmonary artery to travel to the lungs (capillaries) to get oxygenated
- The oxygenated blood is then pushed through the pulmonary veins back to the left atrium
- blood is then pumped through the bicuspid valve (mitral valve) into the left ventricle
- the oxygenated blood then gets pushed through the aortic valve into the aorta to travel to the rest of the body (capillaries)
- the process then repeats
81
Where is blood located?
- mostly in the veins and venules
- capillaries
- heart
- pulmonary blood vessels
- systemic arteries and arterioles
82
Arteries
- aorta
- thick muscle layer
- high-pressure blood
83
Arterioles
- less muscle than arteries
- very innervated(signals) to control muscle contraction
- main BP regulator
84
Capillaries
- no muscle (no contraction)
- cannot withstand high BP
- max movement
85
Venules
- main site of lymph crossing from blood to lymph nodes
- thin smooth muscle
86
Veins
- thin-walled
- pretty muscular
- easy expansion and recoil
87
Autoimmune Disease
- the body cannot recognize self
- own body destroys cells
88
Suppression of T-helper cells (3rdLoD)
- T suppressor cells suppress production of T helper cells
- allows tolerance to self-antigens
Too little:
- autoimmune disease, graft rejection, allergies
Too much:
- cancer, incidence of infectious disease
89
Relationship between surface area and velocity
- higher velocity lower surface area - aorta, arteries - directed and fast
- low velocity higher surface area - capillaries - optimal exchange
90
Cardiac Output
heart-rate x stroke-rate
- blood per contraction/min
Normal = 5L/min
Exercise = 25L/min
*During exercise majority of blood flow goes to skeletal muscles
91
Veins against gravity
Facilitated by:
- pressure gradient (allows blood to flow)
- expansion of thoracic cavity during breathing (dec BP)
- contracting skeletal muscles
- valves (prevent backward movement)
92
Varicose Veins
- valve malfunction
- blood pools and backwards blood flow
- generally in calves and thighs and superficial (visible) veins
93
Heart signal conduction
Cardiac muscle is myocardium
Neural input:
- autonomic/involuntary
Neural conduction:
- Gap-junctions
- fast and contract as a unit
Metabolism: - high oxidative capacity
- many mitochondria (35% of volume)
- fatigue resistant
-
94
Heart Valve Controls Blood Flow
LUB - closing AV valves, tricuspid and bicuspid (mitral valves)
DUB - closing of semilunar valves, pulmonary and aortic valves
95
Heart Valve Problems and Artificial replacements
Stenosis:
- narrowing of blood vessels
- causes thickening of valves
- will not open properly
- maybe at birth, due to calcification, or scarring from rheumatic fever
- cause fatigue, shortness of breath, exercise tolerance, heart failure
Artificial Valves:
- durability - last 1000s of years
- clot formation - requires consistent anticoagulant therapy (clotting)
- can get stuck
- resistance to flow
- vulnerable to backflow and regurgitation
Biological Valves:
- usually porcine (pigs)
- need immunosuppressive drugs
96
Cardiac Cycle
Atrial Systole
- both atrium contracting
Ventricle Systole
- both ventricles contracting
Early diastole
- atrium and ventricle relaxed (fill passively)
Later diastole
- continue filling passively
97
PRELOAD and AFTERLOAD
Pre - initial stretching of cardiac myocytes pre contraction (ind V dec P - allows air to come in) - how much does it stretch?
After - the pressure the heart has to work against to eject blood in systole - how much pressure do the ventricles generate?
98
120/80
120 - contraction - systole
- systolic pressure = max pressure (contraction of the ventricle)
80 - relaxation - diastole
- diastolic pressure = min pressure
99
Conduction through Heart (process)
Heart - individual cardiomyocytes connected to intercalated discs that work in unison
1) SA (sinoatrial) node
- pacemaker (generates electrical pulses)
2) AV (atrioventricular) node
- conducts signals btw chambers
3) Bundle of His (middle of heart)
- transmits signals to ventricles
4) Branches from His (spread left and right down to muscle at the bottom)
- transmits signal
5) Purkinje fibers (spreads left and right down through muscles at bottom)
- transmits signal
* intercalated disks connect all these signals and propagate to coordinate rhythmic function
100
Heart Miscommunication
1) abnormal SA(pacemaker) node firing
- tachycardia (fast)
- bradycardia (slow)
2) Blocks
- e.g blocks AV node
- can slow or prevent signal propagation from A to V
- ventricles may contract independently (bundle of His, 40 bpm)
3) Fibrillations - cells polarize independently
- Atrial Fib - arrhythmia, quivering or irregular heartbeat
- Ventricular Fib - most serious, vent holds oxygen-rich blood, can be life-threatening, unconsciousness
101
Signalling and the Nervous Systems (cardiac)
Sympathetic (norepinephrine)
- increases heart rate
Parasympathetic (acetylcholine)
- decreases heartrate
Epinephrine
- increases strength of contraction
Rest to Exercise
- heart rate to nearly 200bpm (220 - age)
- cardiac output from 5L to 25L (or more if athlete)
102
Hypertrophy
Hypertrophy: a reaction of the muscles ion the heart to enlarge in response to some stimuli such as constriction of the blood vessels and increased activity
Bad:
- constriction of blood vessels
- increased BP
- the heart must work faster to overcome
Good:
- athletes heart
- response to increased exercise
Endurance Athletes:
- increased left ventricle chamber, increased cardiac output
Weightlifting:
- increased left ventricle wall and septum thickness
- to overcome increased afterload (holding breathe)
103
Atherosclerosis
- narrowing arteries
- causes heart attack or stroke
Causes:
- plaque development (calcified fat deposits) in movement systems
- thickening of walls
- triggered by damage that causes inflammation
- Inflammation can cause blood clots
- eventually may lead to heart attack or stroke
Risk Factors:
- increased blood lipids (plaque build-up)
- hypertension (high BP)
- inflammatory mediators (C reactive protein)
- diet (trans/saturated fats)
- smoking
- inactivity
- obesity/diabetes
- age, genetics
Treatment:
- Bypass: replacing an affected artery with a non-affected vein
- usually uses saphenous vein or radial artery (can use vein for artery if needed)
- Catheter: inserts a balloon, blows up balloon to inflate, leaves a stint to push and keep plaque at the side
104
Vasoconstriction
- alpha receptors on arteries
- NEPN and EPN bind to alpha-adrenergic receptors
- causes constriction (increased BP)
105
How is BP affected by Cardio
Does not change much due to:
- dilated arteries/veins to skeletal muscles and heart (inc BP)
- constricted arteries to the gut and kidney (dec BP)
106
Vasodilation
- blood vessels in skeletal muscle do not have alpha receptors
- NEPN and EPN bind to beta-adrenergic receptors found in arteries and skeletal muscles
- dilates vessel
- increased blood (dec BP)
107
Weightlifting on BP
- weightlifters hold their breathe while lifting (Valsalva maneuver)
- this increases the P in the thoracic cavity
- temporarily increases BP (helps protect spine) and slows heart rate (lightheaded)
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GI Tract
Oral Cavity - esophagus - stomach - SI - colon - rectum
- very exposed to the outside environment and toxins
- can expel noxious substances (vomiting, diarrhea)
- specialized immune system (T-cells), localized to the intestinal mucosa (payers patches and mesenteric lymph nodes)
- has sphincters to segregate functions
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Unique properties of the GI tract
- long and folds
- high surface area
- variable transit time for ingested meals (30-80hrs total)
5-8 in stomach and small intestine, rest in colon
- has gut microbiota to protect against pathogenic microbes
- has its own little nervous system
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Processes of the GI tract
1) motility
2) secretion (saliva, mucous, antibodies, digestive enzymes, bile, bicarbonate
3) digestion
4) absorption (H20 and nutrients)
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Cephalic Phase of Digestion
Digests carbs and fats
1) chewing (mechanical) - softens food
2) Secretions in response to sensory stimuli (under autonomic control) - amylase (breaks down starch), lingual lipases (break down lipids/fats)
*No protein digestion yet
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Gastric Phase of Digestion
Digests proteins and fats
- The lining includes many cell types that secrete many different enzymes.
- most cells are signaled by acetylcholine
- chief cells release pepsinogen (gets turned into pepsin and digests proteins), and gastric lipases (digests fats)
- parietal cells release HCL (kills bacteria, activates pepsin)
- mucous cells release bicarbonate (protects cell barrier btw lumen and epithelium)
- amino acids absorbed get transferred via the hepatic portal vein to the liver where they are used for the synthesis of proteins for the liver and other organs
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Small intestine and accessory organs
The pancreas (attached to the small intestine) - releases inactive enzymes (like trypsinogen)
*enzymes get activated in the small intestine by enterokinase in the brush border (e.g from trypsin - protein digestion)
Gallbladder - stores bile for fat digestion
Liver - produces bile
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Small Intestine Absorption
Brush border - villi and microvilli used to increase SA for absorption
Secretions due to food entering:
- Bicarbonate (fm intestinal epithelium, and pancreatic secretions)
- digestive enzymes (fm pancreas)
- Bile acids (fm liver/gallbladder)
Enzymes on lumin of SI
- disaccharidases - break down disaccharides (maltose, sucrose, lactose)
- amino peptidases - break down peptides
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Carbohydrate Absorption and Transport
Maltose - 2 glucose (maltase)
Sucrose - fructose and glucose (sucrase)
Lactose - galactose and glucose (lactase)
Starch - multi glucose's
Disaccharides on epithelial break disaccharides into smaller units (glucose, fructose, galactose)
Galactose and glucose are absorbed using active transport (Na/K ATPase)
- through brush border (coupled with NA)
- into the bloodstream (Na/K ATPase)
Fructose is moved through facilitated transport
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Lactose Intolerance
Lactase Deficiency
- lactose entering the large intestine causes symptoms
*lactase and lingual lipases are highest at birth
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Peptide and Amino Acid Transport
proteins broken down by peptidases into peptides that are then broken further into:
1) di and tripeptides (absorbed via cotransport with H+)
2) Amino acids (absorbed via cotransport with Na+)
3) small peptides (carried intact via transcytosis)
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Allergies
The absorption of full proteins due to intestinal damage may cause leaky gut (space btw tight junctions)
- allows in full proteins (foreign)
- foreign material causes an immune response
- the body then recognizes this protein and fights it every time it enters the body
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Emulsifying Fat
Fat is nonpolar so it does not mix well with water (forms large bubbles)
Fats include:
- triglycerides
- lipids
- phospholipids
- Bile salts are amphipathic so they can interact with water and fats to create smaller bubbles (micelles)
- creates a larger surface area which allows more contact with pancreatic lipases
- enzymes break down micelles into monoglycerides and fatty acids which can freely cross the brush border (into interocytes)
- once inside they reassemble into triglycerides and package as chylomicrons (proteins to allow travel in blood)
- too large to enter capillary so first enter lymphatic system then eventually get to capillary
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What is chyme?
- enters from the ileum into large intestine
- unabsorbed nutrients
- hormones and chemical messengers
- soluble fiber (provides food for bacteria) - can be broken down by enzymes
- insoluble fiber (broken down by bacteria, not enzymes)
- excretion products from the liver
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What happens in the LI
1) epithelium absorbs water and simple ions (Na, K, Mg, Ca)
2) microbes digest - breakdown via fermentation to produce short-chain fatty acids
3) microbes can make vitamins by breaking down fiber
4) microbes produce gas as a product of fermentation
5) getting new alive microbes can multiply and benefit LI - eating probiotics like yogurt can increase beneficial bacteria
*exercise can alter microbiomes in gut
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Role of Microbes in large intestine
Microbes in LI
- ward off unwanted pathogens
- break down fibers
- break down nutrients (breakdown via fermentation to produce short-chain fatty acids)
- produce vitamins (by breaking down fibers - some vitamins can act like hormones - regulate hormones)
- produce gases as a product of fermentation (CO2, CH4, H2S)
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Types of Hunger
Homeostatic - driven by depletion of E-stores
Hedonic - driver to eat to obtain pleasure
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What is the energy distribution system?
Energy production from 3 sources (ATP-PC, glycolysis, oxidative) responds to demands and signals to provide energy for all body functions. This occurs in all cells.
ATP (J, cal)
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Pathways of 3 Macronutrients (Oxidative)
- Carbs and Fats produce the most ATP bc proteins have many other functions in the body (enzymes, structure, etc)
- Proteins can still produce ATP but they are usually not used this way
(glycolysis) Carbs - glycogen - glucose - pyruvate - Acetyl CoA - Krebs cycle
(oxidation) Fats - beta-oxidation of free fatty acids (not in lipoproteins) - Acetyl CoA - Krebs Cycle
*NADH and FADH2 produce reducing equivalents which are used to supply h+ and e- to the ETC to produce ATP
ATP comes directly from:
- glycolysis
- krebs
- ETC
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Anaerobic ATP production
1) phosphocreatine degradation
- PCr is stored in muscles with a bit of ATP
- when this is degraded the ATP is used
- ADP then reacts with P to regenerate ATP
2) Glycolysis (anaerobic)
- glucose - pyruvate - lactate (produces a burning feeling in limbs)
*both are pretty inefficient and only last a short period of time (9-10s ) - sprinting
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Storage of Nutrients
Fat - stored as triglycerides in adipose tissue
Carbs - stored as glycogen
- glyc in the liver (most concentrated cuz smallest organ) - 150g
- glyc in muscle - 350g
- only 30g of GLUCOSE in blood
(must be maintained in a narrow range so breaking down glycogen regulates)
Protein - large potential energy source but only used in starvation or caloric deficit
- stored in muscles
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Carbs vs. Fats as Fuels
Carbs:
- provide ATP faster
- can generate ATP anaerobically (faster)
- hold water, more heavy, less energy-dense
Fats:
- More energy-dense
- slightly slower at ATP generation
- cannot anaerobically generate
- most abundant energy reserve
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Absorptive State
3-4 hours after a meal (anabolic)
Carbs
- in blood
- oxidized to produce ATP
- stored as glycogen in the liver and muscles
Fatty Acids
- can be oxidized to make ATP (less common)
- stored in the liver and adipose tissue as triglycerides
Amino Acids
- oxidized to make ATP
- stored as proteins in muscles and other cells
* excess calories in the form of glucose and amino acids can be converted into fat!
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Postabsorptive Stage
Catabolism
Carbs:
- liver - produces glucose via glycogenolysis to make ATP
- Muscles - produce glucose to then produce lactate and pyruvate which can be used to produce more glucose (gluconeogenesis)
Fatty Acids:
liver and adipose tissue
- fatty acids can by beta oxidized to make ATP
- glycerol can make glucose
- fatty acids can be used to make ketone (are used in absence of glucose to fuel body and oxidized to ATP)
Proteins:
- muscles and other cells - make amino acids that can be oxidized to ATP
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Regulation of Blood Glucose Insulin and Glucagon
Normal fasting 4-5.5mM
Fasting Hyperglycemia: above 7mM
- can cause glycosylation of amino acids in kidneys, eyes, and nerves (adding glucose)
Fasting Hypoglycemia: about 3.5mM
- the body cannot function
* overall maintain body function and osmotic balance
Insulin:
After meal (high insulin, low glucagon)
- high blood glucose
- beta cells in the pancreas secrete insulin
- muscles - increase glucose uptake
- liver and muscles - increase glycogen synthesis, decrease glycogenolysis
- liver - reduce gluconeogenesis
- adipose tissue - reduce lipolysis, decrease plasma fatty acids (to make glucose used)
Glucagon:
Fasting (low insulin, high glucagon)
- low blood glucose
- alpha cells in the pancreas secrete glucagon
- liver - increase gluconeogenesis, and glycogenolysis
- adipose tissue - increase plasma fatty acids, increase lipolysis (glucose is spared)
*glucose is important! It is spared for the nervous system
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Changes to E distribution System during exercise
As intensity increases, fuel comes from muscles
Low intensity (walking, jogging) - blood glucose, fatty acids, some muscles triglycerides and glycogen
Mid Intensity (jogging/running 60-90% VO2) - muscle glycogen and triglycerides, also blood glucose and fatty acids
High Intensity - muscle glycogen, phosphocreatine (PCr)
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Longevity Genes
Genes that affect how long we live have a huge effect on ageing (e.g, some inflammatory genes, density of bones)
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Single Nucleotide Polymorphisms (SNPs)
Mutations to a single nucleotide that are very common in a population
- most commonly SNPs
- create genetic variation amount species
- all of us are different/ have diff alleles (not necessarily phenotypically)
*SNPs are very common even within a single chromosome
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Inflammation and Aging
- Increased inflammatory cytokines as someone ages
- This can contribute to many diseases like alzheimers, cardiovascular disease, arthritis
Specific example:
- IL-6 (interleukin) - an inflammatory cytokine
- when higher concentration in plasma is linked to higher mortality rates
- polymorphism in the promotor region of IL-6 increases IL-^ in plasma
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Mouse Model for Aging
Mice genetically engineered to carry mutations in mt DNA polymerase gamma
- mice show accelerated signs of aging after 25 weeks
- proof reading ability is lost
* connection btw mt DNA mutations and aging phenotype
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Exercise with the mt mouse model
3 groups: placebo, with mt mutations, with mt mutations and 5 months of exercise
- mice in group 3 showed decreased levels of DNA mutations, higher brain weight, and increased muscle weight when they exercised compared to mice in group 2
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Caloric restriction
- 20-40% reduction in daily energy intake without malnutrition
- 1935 - severe food restriction extended healthy lifespan in rats
- shown in yeast, worms, fruit flies, mice, rabbits, dogs, and monkeys
*no conclusive evidence in humans!!!
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Drugs vs. lifestyle: preventing diabetes
diabetes prone subjects studied over 4 years
2 groups: metformin, lifestyle modification, and placebo
lifestyle changes:
- 150 min/week of moderate exercise
- follow food pyramid
- goal: lose 7% of initial body weight
Results highest to lowest incidents of diabetes:
highest: placebo
metformin
lowest: lifestyle
*lifestyle had a 58% reduction in diabetes incidence vs placebo
