The physiology in general is an integrative science that deals with complex living organisms, from molecules and cells to organs and organ systems level.
The physiologist is going to ask two questions:
- How does the organ and the organ system work?
- What's the advantage that this organ system provides to the body?
- Differentiated cell - specialized function.
- Tissue - group of cells with related function: muscle, nervous, connective, epithelium.
- Organ - functional unit.
- Organ system - several organs act together to perform specific function:
- Skin - barrier
- Entry - respiratory & GI
- Transport - CV & diffusion
- Exit - renal & GI
Fluid compartments:
- Body Weight = 70kg
- Total Body Water (TBW): 60% = 42kg
- Inter-Cellular Fluid (ICF): 66.6% = 28kg (cytoplasm) high Potassium (K), low Sodium (Na).
- Extra-Cellular Fluid (ECF): 33.3% = 14kg (surrounds cells, is an interface with external environment)
high Sodium (Na), low Potassium (K).
- Interstitial fluid (IS): 75% = 10.5kg (outside blood vessels)
- Intravascular fluid (IV): 25% = 3.5kg (inside blood vessels)
- Total Body Water (TBW): 60% = 42kg
Equilibrium between IS and IV:
- No net transfer of substance or energy
- No barrier to movement
- No energy expenditure to maintain
Steady state between ICF and ECF:
- Input = Output
- Requires energy to maintain
Homeostasis - the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes.
Stability of internal variables is achieved by balancing inputs and outputs to the body and among organ systems.
5 Types of Homeostatic control:
- Local response: occurs at target cell, e.g.
- a neighboring cell sends a chemical that reached another cell.
- gap junction (nexus) e.g. calcium flow in heart muscles that enables synchronous contraction and relaxation.
- Reflexes: response made at a distance from target cell (Body uses reflex loops to maintain homeostasis: sensors send
signals to the brain where there are set points for different parameters, if the value from the sensor is below or
above a set point it sends a signal to restore the parameter (similar to temperature control in a room)).
- Endocrine response (hormones are released into blood).
- Neural response.
- Tonic control:
- Smooth muscles of blood vessels can constrict or dilate them to increase/decrease blood pressure, which is needed to maintain homeostasis in some situations.
- Antagonistic control:
- Sympathetic and parasympathetic nervous systems can increase/decrease heart rate.
- Circadian rhythms (affected by sleep/wake cycles):
- Growth hormone release during early sleep, falls when we are waking up.
- Cortisol increases just before you wake up.
- Body temperature decreases when we sleep.
Transporters, Pumps and Channels:
- Movement of a solute across the lipid bilayer (cell membrane) is dependent on its size, charge, and solubility.
- Net flux (movement) of a solute is determined by gradients.
- A permeable solute crosses the membrane by simple diffusion (slow), moving down its concentration gradient.
- A non-permeable solute crosses the membrane by facilitated diffusion (fast) using transporters. This process requires a gradient, is saturable, and is specific.
- Primary active transport moves a solute against its concentration gradient. This mechanism requires energy (ATP).
- Secondary active transport couples the activity of a co-transporter with a pump. This is used for transcellular transport of a solute.
Solute and Water Transport:
- Aquaporin - transporter that allows the movement of water across cell membrane.
- Osmolarity - number of molecules per volume.
- Tonicity - tonicity is the relative concentration of solutes dissolved in solution which determine the direction and extent of diffusion. Accounts for number of non-penetrating molecules per volume.
- When you inject isotonic (same concentration of non-penetrating molecules per liter) into the blood, ECF volume increases, ICF volume doesn't change, total body water increase.
- When you lose isotonic fluid during diarrhea, ECF volume decreases, ICF volume doesn't change, total body water decreases.
- When you eat a lot of salty food, ECF volume increases, ICF volume decreases, total body water stays the same.
- When you sweat (hypotonic loss, only water is lost), ECF volume decreases, ICF volume decreases, total body water decreases.
Cell Types:
- Neurons (has dendrites, from which signals are coming to the neuron, and axon, through which signal is send away to other neurons)
- Glial cells - provide structural and metabolic support for neurons (e.g. insulate the neurons)
Membrane potential:
- ATPase moves 2 Potassium (K) ions inside the cell and 3 Sodium (Na) ions outside the cell.
- In addition, Potassium leak channels allow greater movement of Potassium, comparing to Sodium through the Sodium leak channels.
- These factors create net negative potential on the cell membrane.
- Nerotransmitters open Na or K channels on the membrane, which cause inflow of Na inside the cell and depolarization (potential becomes positive) or repolarization (back to negative) of the cell.
Action potential:
- Voltage-gated channels on the membrane are open to Na and K when a certain potential threshold is reached. Na channels open before K channels. The potential thus propagates through axon which is called action potential.
- Graded potential is integrated via dendrites on the body, if the sum of potential reaches the threshold on the initial segment it gets propagated through the axon.
- When the Action Potential reaches the axon terminal, voltage-gated Calcium channels are open and allow Calcium to go inside the terminal, make vesicles with neurotransmitter to fuse with the membrane and release the neurotransmitter into the synaptic cleft.
Types of synapses:
- Cholinergic
- Nicotinic (skeletal muscle, brain).
- Muscarinic (heart, smooth muscle, glands, brain).
- Adrenergic - bind epinephrine and norepinephrine (heart, smooth muscle, glands)
Nervous System Organization
The nervous system is composed of the brain, spinal cord, cranial nerves (emerge directly from the brain) and spinal nerves.
The Senses
- Somatosensation
- Pain is detected by receptors in skin, muscle and bones and visceral (in organs) receptors. nerves detecting chemicals released by damaged cells and immune cells.
- Temperature. thermoreceptors (ion channels activated at certain temperatures)
- Touch, pressure. mechanoreceptors.
- Proprioception (joint capsule, tendon, and muscle stretch). mechanoreceptors.
- Special senses (receptors confined to a specific organ and are associated with cranial nerves)
- Vision - detects the shape and color of objects and the movement of objects int he environment. Light is detected by different cells (rods - more sensitive to light as there are more of them, cones (blue, red, green cones)) in the eye and sent via the optic nerve to the visual cortex for processing.
- Hearing - sound waves are detected by eardrum, connected via middle ear (3 bones) to cochlea via oval window, where there is fluid. Vibraion in fluid is detected by hair cells which cause action potentail in nerve fibers. Frequency is determined by which area of cochlea vibrates most. Volume is detected by aplitude of hair vibration.
- Vestibular System (Equilibrium) - located near to inner ear (cochlea), 3 perpendicular hemicircle tubes. Detects the position and the motion of the head in space.
- Chemical Senses
- Taste - taste buds are located in the tongue. Chemicals dissolved in liquid are detected by taste receptor cells located in taste buds. 5 basic tastes (umami, salt, sugar, sour, bitter) correspond to 5 chemicals the taste cells detect (glutamate, sodium (Na+), glucose, hydrogen ions (H+), plant alkaloids)
- Smell - results from the activation of olfactory receptors (~400) in the nose. We can discriminate ~10,000 odors as combination of 400 receptors.
- Visceral stimuli (pH, O2 content of blood, osmolarity, blood glucose.
Sensation - sensory information that reaches the brain
- what stimulus is (each nerve fiber is responsible only for 1 type of stimulus)
- where it is
- how strong (determined by action potential frequency)
Perception - how we interpret the sensation
Somatic Nervous System controls locomotion, fine movements, body posture, and equilibrium by acting on motor neurons in the spinal cord that innervate the skeletal muscles.
A motor neuron and the muscle fibers that it innervates constitute a motor unit.
Motor neurons have cell bodies located in grey matter of the ventral horn of the spinal cord. The spinal cord contains interneurons which play a role in coordinating the responses of antagonistic and synergistic muscles to carry out intended movements as well as reflexive movements initiated by sensory receptors.
Muscle Stretch Reflex (knee jerk reflex) - when the rubber hammer is striking the patellar tendon under the knee cap it's tugging on the quadricep muscle. The afferent neuron coiled around the muscle spindle sense stretch ( muscle length and speed of stretch). It acts in reciprocal innervation causing contraction of stretched muscle and relaxation of antagonistic muscle.
Walking movements are initiated by central pattern generators in the spinal cord. Interneurons coordinately drive antagonistic muscles in withdrawal and crossed-extensor reflexes and can be modified by sensory feedback.
Sympathetic and Parasympathetic Nervous System
All muscles are composed of two sets of overlapping filaments, actin and myosin, the relative sliding of which produces shortengin and generates force. This process involves cross bridge formation between actin and myosin and uses ATP.
Action potential travles throug muslce membrane and through T-tubules, causing Calcium to be released from sarcoplasmic reticulum to muslce fiber which ignites the reaction causing fiber contraction.
Tension of the muscle increases with the increase of action potential frequency. A single AP of 5ms causes a muscle twitch of 100ms.
The tension is highest when the sarcomere length is equal to the sarcomere length in a resting muscle.
Muscle fuels:
- Creating phosphate - donates phosphate to convert ADP to ATP in the first 8-10s of muscle activity.
- Anaerobic metabolism (glycolytic) - produces ATP and lactic acid by burning glucose and muscle glycogen. Lasts for about 1.5 minutes.
- Aerobic metabolism (oxidative) - produces ATP, CO2 and water by burning blood glucose and fatty acids. Unlimited.
Rigor mortis - or postmortem rigidity, is the third stage of death. It is one of the recognizable signs of death, characterized by stiffening of the limbs of the corpse caused by chemical changes in the muscles postmortem. In humans, rigor mortis can occur as soon as four hours after death.
After death, respiration in an organism ceases, depleting the source of oxygen used in the making of adenosine triphosphate (ATP). ATP is required to cause separation of the actin-myosin cross-bridges during relaxation of muscle. When oxygen is no longer present, the body may continue to produce ATP via anaerobic glycolysis. When the body's glycogen is depleted, the ATP concentration diminishes, and the body enters rigor mortis because it is unable to break those bridges.
Types of muscle fibers:
- Slow-oxydative fibers - resist fatigue (muscles for posture).
- Fast-oxydative-glycolitic fibers - resist fatigue (muscles used in walking).
- Fast-glycolitic fibers - used for bursts of strong force (muscles used in jump).
Most skeletal muscles include all three fiber types.
Slow-oxydative fibers are recruited by the system first. If more force is required Fast-oxydative-glycolitic fibers get involved. Lastly Fast-glycolitic fibers are used for maximal force.
Training doesn't increase the number of muscle fibers (it's pre-determined genetically). Instead, it increases the size of muscle, by growing the number and size of capillari in muscle tissue and mitochondria in muscle fibers.
Smooth muslce:
- Involuntary, non-striated (no sarcomeres) muscle associated with blood vessels and visceral organs (e.g. intestine).
- Contains overlapping protein myofilaments, actin and myosin, the relative sliding of which produces shortening and generates force. This process is driven by ATP.
- Coupling between the membrane potential and contraction is mediated by calcium ions. Calcium regulates myosin to enable cross bridge formation and contraction.
- Regulated by the autonomic nervous system (via norepinephrine). Some smooth muscle is regulated by stretch or by paracrine factors.
- Some smooth muscle exhibits fused tetanus and tonic contraction.
Cardiac muscle:
- involuntary, striated type muscle
- Contains overlapping protein myofilaments, actin and myosin, the relative sliding of which produces shortening and generates force. This process is driven by ATP.
- Coupling between the membrane potential and contraction is mediated by calcium ions. Calcium regulates myosin to enable cross bridge formation and contraction.
- Regulated by the autonomic nervous system.
- Cardiac muscle contracts in unison and does not develop fused tetanus.
Pacemakers:
- Sino-Atrial (SA) node fires at 100 beats/min.
- Atrial-Ventricular (AV) node pauses electrical signal; fires at 40-60 beats/min.
- Bundle of His and Purkinje fire at 25-45 beats/min.
- P-wave is atrial depolarization.
- QRS - ventricular depolarization.
- T - ventricular depolarization.
- PR segment - time between SA and AV node firings.
- ST segment - phase 2 of fast action potential.
Sympathetic NS speeds up heart rate and it acts via Beta-1 adrenergic receptors. Parasympathetic NS decreases heart rate, acts through the vagus innervation to muscarinic receptors in the heart.
- Left ventricle has thickest walls because it's pumping blood through the body.
- Right ventricle is smaller because it's pumping blood through lungs.
Cardiac Cycle (Wiggers diagram)
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The heart makes the "lab-dab" sounds for each cycle.
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The 1st lab is the closing of a atrioventricular valves.
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The 2nd dub is the closing of semilunar valves.
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End-diastolic volume (EDV) in each ventricle is 125 ml.
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During one systole, the volume of blood ejected is the stroke volume (SV). SV is usually 70 ml.
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The volume remaining is end-systolic volume (ESV). Usually 55 ml.
Cardiac Performance
- Cardiac output (CO) volume pumped each minute.
- CO = SV * HR
- HR is usually 72 beats per min. CO = 5 L/min.
- The ejection fraction (EF) is the percentage of blood pumped from the heart in each beat.
- CO increases with increased fill of the ventricles (venous return) and/or increased sympathetic stimulation.
Circulatory System
Pressure and Pulsatility
- Arteries are low resistance conduits that maintain pressure during diastole and distribute blood to organs.
- Arterioles are the dominant site of resistance to blood flow within the organ.
- Capillaries are the site of exchange. Balance between hydrostatic and oncotic forces determines the direction of fluid movement either into or out of capillaries.
- Veins are the low resistance conduits for venous return and volume reservoirs.
Edema - an abnormal accumulation of fluid in the interstitium, located beneath the skin and in the cavities of the body. Six factors can contribute to the formation of edema:
- increased hydrostatic pressure;
- reduced colloidal or oncotic pressure within blood vessels;
- increased tissue colloidal or oncotic pressure;
- increased blood vessel wall permeability (e.g., inflammation);
- obstruction of fluid clearance in the lymphatic system;
- changes in the water retaining properties of the tissues themselves. Raised hydrostatic pressure often reflects retention of water and sodium by the kidneys.
Blood pressure is measured with a device called sphygmomanometer and a stethoscope:
- The cuff is inflated until the pressure is high enough to block the blood from in the arm.
- When pressure in the cuff of the sphygmomanometer is higher than the systolic pressure there are no sounds.
- As the pressure in the cuff decreases gradually, the first Korokoff sound appears at the time when the pressure in the cuff is equal to the systolic blood pressure.
- The sounds will first increase in volume, then decrease, until the point when they disappear completely. This marks the diastolic blood pressure.
Reflex loop
- Cardiac output (CO) is matched with tissue blood flow by maintaining mean arterial blood pressure (MAP) relatively constant.
- Baroreceptors act as short term regulators of arterial blood pressure. They provide sensory information to the cardiovascular center in the medulla (MCCC). Autonomic outflow from the MCCC maintains blood pressure constant.
- Total blood volume can change the end diastolic volume of the ventricles and thereby change stroke volume.
- Hemorrhage reduces EDV leading to hypotension. Normal compensatory response to hemorrhage is vasoconstriction of arteries and increased heart rate.
- Hypotension can result from either a sudden postural change or from prolonged quiet standing. The compensatory response is as stated above for hemorrhage.
- Aerobic exercise increases CO (up to 30 L/min) but reduces TPR (total peripheral resistance) so MAP remains almost constant. In weight lifting, CO, TPR, and MAP increases.
- Failure of the heart to maintain normal CO leads to increased TPR to maintain MAP.
- Compensation for decreased CO caused by heart failure (weak heart) includes increase in HR and TPR, vasoconstriction of veins, and retention of water by the kidneys.
Primary Roles:
- Provide O2 for oxidative metabolism which generates ATP and CO2.
- Regulate the body's H+ concentration (pH).
- Host defense - 70 m2, 10k liters per day.
Alveolar-capillary interface - blood-gas interface. This is also called respiratory membrane. ~70 sqm. for gas exchange.
- Frequency of ventilation around 10-18 breaths per minute.
- Tidal volume around 0.5 liters per breath.
- Minute ventilation around 5L/min.
- During heavy exercise air flow can increase 20-fold and blood flow 3-fold.
Compliance is the change in lung volume after a change in transpulmonary pressure. It's a measure of lung distensibility.
There are 2 types of lung desease:
- Restrictive (fibrosis) - the lung has low compliance (i.e. hard to inflate).
- Obstructive (emphysema) - the lung has high compliance (i.e. hard to deflate) due to loss of elastic fibers.
- PA - Pip determines lung size and PA - Patm determines air flow.
- Airway resistance increases during expiration. During forced expiration, when intrapleural pressures become positive, small airways are compressed (dynamic compression) and may even collapse.
Pulmonary function tests:
- Forced vital capacity (FVC) - maximal volume of air exhaled after a maximal inspiration.
- Forced expiratory volume in 1 sec (FEV1) - fraction of the total forced vital capacity expired in 1 sec. Normal individuals expire approx. 80% of their vital capacity in this time.
Oxygen (O2) transport:
- Alveolar PO2 is determined by the PO2 of atmospheric air, the alveolar ventilation rate, and RQ (respiratory quotient).
- Oxygen transport is not limited by diffusion. 99% of oxygen is bound to hemoglobin.
- Oxygen is transported in blood by binding to Hb which increases its concentration 70-fold compared to its intrinsic solubility.
RQ (respiratory quotient) = CO2 eliminated / O2 consumed. Can be used to know the main metabolic paths in the body. For Carbohydrates (require less oxygen to be fully metabolized) RQ is 1; for fats (require more oxygen to be fully metabolized) RQ is 0.7.
Carbon dioxide (CO2) transport:
- 60% of CO2 is in blood as bicarbonate ion (HCO3-).
- H2O + CO2 = H2CO3 = HCO3- + H+.
- 30% of CO2 is bound to hemoglobin.
- 10% dissolved in plasma (PCO2).
CO2 is very soluble in blood and needs no carrier. This difference explains why CO2 concentration in blood is directly proportional to minute ventilation while O2 is not.
- Bottom part of the lung is perfused by blood more (because of gravity) and ventilated more (because lung are stretched less) than the top part.
- Bottom part of the lung is perfused by blood more than it's ventilated.
- Normal lung function requires matching ventilation to perfusion. Ventilation without perfusion is equivalent to a shunt that bypasses the lungs.
- Intrinsic mechanisms work to match ventilation and perfusion such as hypoxic pulmonary vasoconstriction (at high altitudes when pressure of O2 is low the body constricts blood vessels perfusing the lung, this increases the pressure so that the capillary start leaking and causes massive pulmonary edema, which can make the problem even worse).
Exercise is the most common cause of increased ventilation in the healthy normal individuals. At maximal exercise, PaCO2 falls and arterial pH falls due to metabolic acidosis.
Regulation of breathing
At rest arterial PCO2 is the most important determinant in the ventilatory drive.
The central chemoreceptors detect changes in arterial PCO2 by sending H+ concentration in the interstitial tissue.
Hypothalamus is a portion of the brain, it integrates afferent signals from the brain, viscera, and circulating levels of substrates and hormones. Pituitary is an endocrine gland inside the brain. Together they regulate energy and water balances, growth, responses to stress, and reproduction in the body.
The pituitary gland is divided into anterior and posterior parts. Anterior pituitary consists of glandular tissue, posterior pituitary consists of neural tissue.
Anterior Pituitary hormones:
| Hypothalamus | Anterior Pituitary | Target organ |
|---|---|---|
| CRH (Corticotropin-releasing hormone) | ACTH (Adrenocorticotropic Hormone) | Adrenal gland |
| TRH (Thyrotropin-releasing hormone) | TSH (Thyroid stimulating hormone) | Thyroid gland |
| GnRH (Gonadotropin-releasing hormone) | LH (Luteinizing Hormone) & FSH (Follicle-stimulating hormone) | Gonads |
| GHRH (Growth hormone–releasing hormone) & GHIH (growth hormone-inhibiting hormone) aka Somatostatin | Growth Hormone | Liver & bone |
- | Prolactin | Breast
Adrenal Gland:
- Cortex:
- Aldosterone (controls salt balances in the body; not controlled by HP axis, produced when K+ increases in blood, causes kidneys to return Na+ and water from urine to blood and excrete K+)
- Cortisol
- controls sugar balances in the body
- regulated by HP axis; peaks at 8AM
- provides fuel
- promotes growth of "beer belly fat"
- is anti-inflammatory and suppresses immune response
- degrades fat, muscle and peripheral fat
- Inhibits growth hormone, thyroid hormone, insulin and sex hormones at target tissues.
- DHEA (weak androgen)
- Medulla
- Epinephrine
- Norepinephrine
Thyroid Gland:
- T3 and T4 are synthesized and secreted by the thyroid gland in response to TSH.
- Thyroid hormones are formed from the hydrolysis of iodinated thyroglobulin.
- Dietary iodine is essential for the hormone synthesis.
- Thyroid hormones are essential for the development of the nervous system, for normal body growth and to regulate basal energy and temperature.
Metabolism in Stress:
Posterior Pituitary hormones:
- Vasopressin (ADH, antidiuretic hormone) - regulated by osmotic and volume stimuli:
(1) rise in plasma osmolarity (plasma Na)
(2) derease of ~10% or more in blood volume)
- acts in kidney to move water from filtrate (urine) to blood to increase blood volume.
- Oxytocin (OTC) - regulated by suckling and cry of infant.
- increases contraction of myoepithelial cells in breast and smooth muscle in uterus.
- "bonding" hormone.
Male Reproductive System
- Chromosomal sex is determined by XX and XY chromosomes.
- Gonadal sex is determined by expression of the SRY gene on chromosome Y (presence of testes or ovaries)
- Phenotypic sex is determined by testosterone receptor gene on the X chromosome.
- Differentiation of germ cells as well as synthesis and secretion of sex hormones are common functions of averies and testes.
- Reproduction in both males and females is controlled by pulsatile secretion of GnRH from the hypothalamus which controls FSH and LH secretion from the pituitary.
- FSH and LH govern germ cell maturation and sex steroid hormone production in both males and females.
- Sex steroid hormones regulate FSH and LH by negative feedback, and are required for fertility and secondary sexual physical characteristics.
Spermatogenesis occurs in testis.
- 40-80 million sperms / ml. <20 million / ml = infertile.
- Maturation = 90 days.
Androgens (Testosterone, DHT):
- Testosterone is responsible for GnRH feedback, spermatogenesis and embryonic differentiation.
- DHT is most important for external virilization and secondary sexual characteristics.
- Steroids delivered by carrier in the blood. Act by changing gene expression (activate transcription).
- Anabolic actions (promotic increased muscle mass).
- Excess testosterone can decrease the size of the testes and decrease sperm count but will increase the size of prostate.
Androgen Dependent Tissues:
- Seminal vesicles - provide fructose rich liquid which is 60% of semen volume.
- Prostate - alkaline secretion provides 20% of semen volume. Enlarges under influence of DHT.
- Secondary sex traits: increased muscle mass, facial hair, deep voice.
Bone expresses aromatase - converts testosterone to estrogen. Estrogen stops longitudinal growth of bones.
Female Reproductive System:
- Differentiation of germ cells as well as synthesis and secretion of sex hormones are common functions of averies and testes.
- FSH and LH govern germ cell maturation and sex steroid hormone production in both males and females.
- As the chosen follicle matures it produces estrogen which increases its own sensitivity to LH (and FSH) and reduces the amount of FSH released by the pituitary. The reduction in FSH leads to the death of less mature follicles.
- In females, a second group of kisspeptin neurons is responsible for the ability of estrogen to cause the LH surge.
Human chorionic gonadotropin (hCG) is a hormone produced by the placenta after implantation. Measured by pregnancy tests.
Enterogastric reflex - a nervous reflex whereby stretching of the wall of the duodenum results in inhibition of gastric motility and reduced rate of emptying of the stomach. It is a feedback mechanism to regulate the rate at which partially digested food (chyme) leaves the stomach and enters the small intestine.
Gastroileal reflex is stimulated by the presence of food in the stomach and gastric peristalsis. Initiation of the reflex causes peristalsis in the ileum and the opening of the ileocecal valve (which allows the emptying of the ileal contents into the large intestine, or colon). This in turn stimulates colonic peristalsis and an urge to defecate.
Gastrocolic reflex - a physiological reflex that controls the motility, or peristalsis, of the gastrointestinal tract following a meal. The gastrocolic reflex's function in driving existing intestinal contents through the digestive system helps make way for ingested food.
Migrating Motor Complex (MMC) - waves of electrical activity that sweep through the intestines in a regular cycle during fasting. The MMC occurs every 90-230 minutes during the interdigestive phase (i.e., between meals) and is responsible for the rumbling experienced when hungry.
- Peristaltic Wave in the Gastric Antrum: https://www.youtube.com/watch?v=o18UycWRsaA
- Intestinal peristalsis: https://www.youtube.com/watch?v=hKQ8eFpUKLs
- Villi of small intestine: https://www.youtube.com/watch?v=SDbjwMS_1vI
GABA (gamma-Aminobutyric acid) is the chief inhibitory neurotransmitter in the central nervous system. Low GABA levels are associated with restlessness, anxiety, insomnia and a poor mood state.
Glutamate is the chief excitatory neurotransmitter in the central nervous system.
Serotonin or 5-hydroxytryptamine (5-HT) is both a mediator and a hormone. First it was discovered in vessel walls, where it causes constriction (thus the name).
Serotonin functions:
- Inhibitory/calming function. Induces sleep.
- Reduces pain sensitivity.
- Inhibits weak neural signals in the brain (helps GABA). Helps to focus on the main task.
- Inhibits negative emotions.
Increasing Serotonin without drugs (there is no direct proof the methods described below work):
- Positive mood inductions.
- Exposure to bright light. Lux. Intensity of light inside a room (320 - 500 lux) is 20 times lower than the intensity of light outside at full daylight (10,000 - 25,000 lux).
- Exercise.
- Diet - foods with high tryptophan content may increase serotonin in the brain (chickpeas, hummus).
A video about Serotonin from a Russian professor (in Russian): https://www.youtube.com/watch?v=oJDATLKNoOY&list=PLuXVSZY9-G53pzp4lboV3DdDslVcwrriJ
https://www.ncbi.nlm.nih.gov/pubmed/11958969
https://www.nutritionsteps.org/
https://www.youtube.com/channel/UCxtgzInwVobygfSimD7N6Ug
https://www.youtube.com/watch?v=__q5nHfro7g&list=PL3IIVyZl0FANpdFMnN2PCN1lWmlyr6lKs
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Correlation doesn't mean causation.
- In Greece researches observed that there very high consumption of olive oil and a very low incidence of cardiovascular desease.
- This doesn't necessarily prove the olive oil prevents cardiovascular desease.
- No, it's possible that a lot of sun in Greece causes a lot of olives and high olive oil consumption, and a lot of sun makes a lot of vitamin D in the skin which protects them from cardiovascular desease.
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Epidemiological evidence.
- Outcomes of a large number of real-life cases and controls, chosen with appropriate and objective criteria, in large enough number.
- The major problem is the presence of confounding factors.
- For example, vegans have lower rates of heart desease. But vegans are usually more healthy in other aspects of life-style, e.g. they have a balanced diet, avoid smoking etc. Thus we can't conclude that avoiding meat prevents heart desease.
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You can always find evidence supporting your hypothesis.
- There are two books based on scientific evidence that suggest opposing ideas:
- The China Study - suggests avoiding meat is good for health.
- The Paleo Diet - suggests eating meat is good for health.
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Risk assessment.
- Some people are afraid to eat unpealed fruits because of pesticides and other chemicals used in production of those. While at the same time eating a lot of saturated fats. The risks associated with eating a lot of saturated fats are much higher.
Key Principles of Nutrition:
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Principle of variety - the more monotonous our diet is, the higher the risk of nutrient deficiencies or imbalances.
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Principle of moderation - we should eat small portions of many different foods.
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Principle of balance - our choice of foods should ensure a healthy proportion of all the different nutrients that we need.
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Common deficiencies:
- Deficiency of Vitamin C (ascorbic acid, present in oranges, sourkraut) causes scurvy.
- Deficiency of Vitamin B-1 (thiamin, present in the external layer of rice) causes beriberi.
- Deficiency of Vitamin B-3 (niasin, present in corn cooked in alcaline solutions like tortillas) causes pellagra.
6 categories of nutrients (lack of these causes desease or death): - Carbohydrates - Proteins - Lipids - Vitamins - Minerals - Water
Non-nutrient bioactives: - fiber, plant sterols, phytochemicals (polyphenols, carotenoids, isothyocyanates)
Function of nutrients: - Energetic - Structural - Regulatory
DRIs (Dietary Reference Intakes) - RDA (Recommended Daily Allowance) - average daily intake of a particular nutrient that meets the needs of 98% of the population. - AI (Adequate Intake) - if RDA can't be set due to insufficient data AI is used. - UL (Tolerable Upper Intake Level) - intake that should not be exceeded. - DV (Daily Value) - percentage of the recommended daily intake, set by FDA.
AMDR (Acceptable Macronutrient Distribution Ranges): - 45% - 65% of energy from carbohydrates - 20% - 35% of energy from fats - 10% - 35% of energy from proteins
Food groups:
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Plant Food
- Fruits
- Vegetables
- Nuts & seeds
- Legumes
- Grains
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Not plants but not animal:
- Mushrooms
- Seaweed Animal Food
- Meat
- Fish
- Milk & Dairy
- Eggs
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For 4 million years our genes where honed for hunter-gatherer life-style.
- They mostly ate fruits, vegetables, meat and fish.
- The food was scarce.
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Only 10,000 years ago agricultural revolution happened.
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Only 300 years ago industrial revolution happened.
https://www.youtube.com/watch?v=KWv5ROe8lZQ&list=PL3IIVyZl0FANAKJSNQQjvLbTz4Pa8oJPY
Effect of nutrients on satiation (насыщенность) and satiety (сытость)
| * | Short term effect (Satiation) | Long term effect (Satiety) |
|---|---|---|
| Fiber | +++ | + |
| Lipids | + | +++ |
| Carbs | ++ | + |
| Proteins | +++ | +++ |
Leptin - hormone released by adipose tissue
- decreases hunger
- its variations regulate hunger in the longer term
- homeostatic regulation.
https://www.youtube.com/watch?v=URAJzOjYjDo&list=PL3IIVyZl0FAN8g3S-oGv0uRn3IOwmDi50
1 kcal = 4,186 kJ - amount of heat required to raise the temperature of 1 kg of water by 1 degree Celcius. 1 cal in nutrition is equal 1 kcal from physics :(
Energy for each nutrient:
- 4 kcal per 1g of carbohydrates.
- 4 kcal per 1g of Proteins.
- 9 kcal per 1g of Fats.
Human body spends energy on:
- Basal metabolism.
- 60% - 70% of total spent energy for a sedentary person.
- Muscle requires more energy so people with higher muscle mass in the body have higher basal metabolic rate.
- Taller people have higher metabolic rate because of larger body surface area.
- Too high or too low environmental temperature increases basal metabolic rate.
- Stress increases basal metabolic rate.
- Thyroid hormones increase basal metabolic rate.
- Thermogenic substances (nicotin, alcohole, caffein) increase basal metabolic rate.
- Physical activity.
- TEF (Thermic Effect of Food) - the energy required to digest nutrients. 4, 4 and 9 kcal for carbs, proteins and fats are already adjusted for TEF.
Energy spent during exercise:
- Heavy weight lifting for 30 mins - 300 kcal.
- Brisk walking for 30 mins - 150 kcal.
- Watching TV for 30 mins - 45 kcal.
Harris-Benedict formula for BMR:
- For men: BMR = (10 × weight in kg) + (6.25 × height in cm) - (5 × age in years) + 5
- For women: BMR = (10 × weight in kg) + (6.25 × height in cm) - (5 × age in years) - 161
To calculate total energy expenditure multiple BMR by PAL (physical activity level):
- Sedentary or light activity. Ex: Office worker getting little or no exercise: BMR x 1.53
- Active or moderately active. Ex: Construction worker or person running one hour daily: BMR x 1.76
- Vigorously active. Ex: Agricultural worker (non mechanized) or person swimming two hours daily: BMR x 2.25
https://www.youtube.com/watch?v=hFMF3lJUcAc&list=PL3IIVyZl0FAMJYbvSa8AV3puK6FvKdEL1
- Monosaccharides
- Glucose
- Fructose
- Galactose
- Disaccharides
- Surose (glucose + fructose)
- Lactose (glucose + galactose)
- Maltose (glucose + glucose)
- Polysaccharides
- Amilose
- Amilopectin
- Glycogen (energy storage in animals)
Humans store a few hundred grams of glucose, mostly in liver and muscle cells.
Hormones:
- Insulin lowers blood glucose when it's too high.
- Is also an anabolic hormone, allows us to store any excess energy coming from food: glucose to glycogen, what's left to fat.
- Promotes cholesterol synthesis in our liver.
- Causes water retention and raises blood pressure.
- Slows down secretion of growth hormone.
- Long-term effects of frequent excessive insulin peaks:
- Insulin resistance
- Hyperinsulinemia
- Type II diabetes (high blood sugar, insulin resistance, and relative lack of insulin) - adult-onset diabetes.
- Glucagon raises blood glucose when it's too low.
Glycemic Index - measures the speed at which carbs contained in a food raise blood glucose. The way it's calculated is first you measure glucose level in the blood for 2 hours after taking 50g of glucose, measure area under the curve, measure glucose level in the blood for 2 hours after taking the amount of food with 50g of carbs in it, measure area under the curve. Divide 2nd area by the 1st area and multiply by 100 to get the Glycemic index.
- Glucose - GI = 100
- White french baguette - GI = 95
- Table Sugar - GI = 68
- Boiled Potato - GI = 63
- Banana - GI = 52
- Mango - GI = 51
- Fructose - GI = 19
- Cabbage - GI = 10
Sorbitol, mannitol, xylitol provide about 2 kcal/g, don't promote tooth decay.
Non-caloric sweeteners:
- Saccharin
- Aspartame
- Acesulfame-K
- Sucralose
- Neotame
- Tagatose
Glycemic Load - Glycemic Index * Carb Content (g) / 100.
Grain's anatomy:
- Soluble fiber:
- Dissolves in water
- Form a gummy gel in water
- Makes stool larger and softer.
- In large amounts has laxative effect.
- Is fermented by gut bacteria. Fermentation products (vitamins, short chain fatty acids) can be absorbed and have positive effects.
- Insoluble fiber:
- Does not dissolve in water
- Is not fermented by gut bacteria.
- Accelerates the transit of stool.
Fiber RDA: 38g (adult men), 25g (women).
Fiber:
- Whole grains, vegetables, skin of fruit: mostly insoluble fiber.
- Pulp of fruit, seaweeds: mostly soluble fiber.
- Legumes, nuts, seeds: both soluble and insoluble fiber.
- Milk, fish, eggs, dairy: no significant amount of fiber.
https://www.youtube.com/watch?v=NUs_aXPtitc&list=PL3IIVyZl0FANkAvQjBBbRdnJ_fGGV3pwM
Lipids - organic biomolecules that do not readily dissolve in water (hydrophobic).
Main Lipid Classes:
- Triglycerides
- Phospholipids
- Sterols
- Cholesterol
- Plant sterols
Fatty acids - key components of triglycerides and phospholipids, and often bound to sterols.
Seven countries study - 1960 - 1970, Ancel Keys observed a positive correlation between high dietary lipids, obesity and CVD.
The Crete Paradox - extremely high fat consumption (>40% of total energy) but low incidence of cardiovascular desease. Might be because they consume less than 10% came from saturated fats and eat a lot of fruits and vegetables.
The Eskimo Case - more than 70% of energy from fats but they are perfectly healthy.
The French Paradox - saturated fat and cholesterol consumption same as in the US, but CVD rates are lower. Is it because the French drink a lot of wine? No. The french are eating a lot of fruits, vegetables, legumes, grains.
Triglycerides
- are the main energy storage in our body. Excess carbs and proteins are converted to lipids and stored in the adipose tissue, but there's no way back.
- are the main fuel for heart muscle but brain and red blood cells can't use it for energy (they use carbs instead).
- protective cusion and body insulation.
- absorption of fat-soluble vitamins and carotenoids.
- satiety.
Fatty acids - main building blocks of lipids.
- saturated.
- monounsaturated.
- polyunsaturated.
Common fatty acids:
Monounsaturated fatty acids:
Trans fatty acids (hard same as saturated fatty acids):
Polyunsaturated fatty acids (the first unsaturated bond is 6 or 3 carbon atoms away from the end of the molecule):
- SFA. Mainly found in food of animal origin. Many of SFA are atherogenic so excess of it in our diet is detrimental.
- MUFA:
- Oleic acid, omega-9 family. Contained in olive oil, peanuts, avocado, macadamia, canola oil.
- PUFA. There are 2 essential fatty acids:
- Linoleic, omega-6 family. Contained in nuts and seeds in general, most vegetable oils (corn oil, sunflower oil).
- Linolenic, omega-3 family. Alpha-linolenic acid is an essential fatty acid for humans.
All other omega-3 acids can be derived from linolenic, however this conversion is slow,
therefore direct EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) intake from food is advisable.
- Alpha-linolenic acid. Contained in walnuts, soy, soy oil, portulaca, flax seeds, flaxseed oil (rancidity!).
- EPA and DHA. Contained in fatty fish (salmon, sardine, tuna), shellfish, crab, shrimp, lobster.
Oxidized/rancid PUFA are very bad for our health - highly cancirogenic and atherogenic. Should store PUFA in fridge, away from light sources, never fry in PUFA.
Omega-3 vs Omega-6 balance:
| Omega-3 (salmon, sardines, walnuts, flax seeds) | Omega-6 (nuts and seeds, corn oil, sunflower oil) |
|---|---|
| Blood fluidity | Platelet aggregation |
| Vasodilation | Vasoconstriction |
| Immunosuppression | Immunity |
| Anti-inflammatory | Pro-inflammatory |
| Pain inhibition | Pain transmission |
| Inhibit cell proliferation | Cell proliferation |
| Less stomach secretion | More stomach secretion |
Fat proportion for good health:
- 20-35% of total energy should come from lipids.
- < 10% from SFA.
- 10-20% from PUFA:
- omega-3 to omega-6 proportion should be 1:2 to 1:4.
- remaining is MUFA>
- no trans fats.
https://www.youtube.com/watch?v=1Caojyxhn2A&list=PL3IIVyZl0FANZrS-BUb7fmLwhKwpyOMDa
- 62% of our body weight is water, 17% is protein.
- Have the key regulatory function: hormones, enzymes, carriers, signalling, antibodies.
- Energy: 4 kcal/g.
Proteins contain nitrogen and our main N source.
Gelatin - 86% protein / dry weight (lacks EAA tryptophan, isoleucine, threonine and methionine). If dogs are fed only gelatine they die within 1 month because gelatin lacks some EAAs.
Amino acids:
- alanine - ala - A
- arginine - arg - R
- asparagine - asn - N
- aspartic acid - asp - D
- cysteine - cys - C - little in legumes
- glutamine - gln - Q
- glutamic acid - glu - E
- glycine - gly - G
- histidine - his - H - essential
- isoleucine - ile - I - essential
- leucine - leu - L - essential
- lysine - lys - K - essential - little in grains
- methionine - met - M - essential - little in legumes
- phenylalanine - phe - F - essential
- proline - pro - P
- serine - ser - S
- threonine - thr - T - essential
- tryptophan - trp - W - essential
- tyrosine - tyr - Y - conditionally essential (can be converted from phenylalanine)
- valine- val - V - essential
Proteins in foods:
-
From animals
-
eggs - 13%
-
fish - 15-23%
-
meat - 15-20%
-
cheese - 25-35%
-
milk - 3%
-
From nuts & seeds
-
peanuts - 26%
-
walnuts - 24%
-
sunflower seeds - 21%
-
sesame seeds - 20%
-
From grains
-
brown rice - 8%
-
quinoa - 14%
-
From legumes
-
lentils - 26%
-
chickpeas - 20%
-
soybeans - 36%
-
2/3 grains and 1/3 legumes complement each other and provide all the amino acids we need.
-
Milk contains proteins that have opioid-like activity and are sometimes absorbed intact. Some people claim that they can't sleep without drinking a glass of milk before bed.
-
Protein turnover is around 250g/day. Most of it is recycled so daily needs for proteins are much less. 0.8g/kg/day for an average adult. More if exercising.
-
Protein in blood albumin maintains fluid balance. It creates osmotic pressure that sucks fluids from intersticial space back into the blood. Lack of albumin causes edema.
-
High-protein, low-carb diets make you quickly lose your weight because you lose a lot of water, which is needed to flush out nitrogen produced by catabolising proteins.
-
Protein absorption from animal sources is over 90%, from vegetable sources 70-90%.
https://www.youtube.com/watch?v=tLGJAL3eKaM&list=PL3IIVyZl0FAPCC7OB7QbumdvaWRTLQ_xC
Vitamins are vital organic (contain carbon) nutrients, do not provide energy, are needed in very small amounts to perform structural or regulatory functions in our body. Their deficiency causes desease.
-
Not all are essential, i.e. vit D can be derived from cholesterol in skin in presence of UV light.
-
Fat soluble vitamins (need dietary fat to be absorbed, can accumulate in tissues esp. liver, toxic if excess intake):
- A ("Eye vitamin").
- Necessary to form rhodopsin, the key molecules that allow vision. If deficient results in night blindness.
- Regulation of gene expression.
- Health of skin and mucous membranes.
- Enhanced ability to fight infections.
- Cancer preventive activity.
- Deficiency symptoms:
- Night blindness, slow adaptation from bright to dim light, dry eyes.
- Dry and rough skin, itches, rashes and acne, follicular hyperkeratosis.
- High susceptibility to infections.
- Sources:
- Retinol (active vit A) in chicken, pig liver, cod liver oil.
- Plant pigments that can be converted to vit A (Carrot, pumpkin, mango, papaya)
- D (colecalciferol) ("Sunshine vitamin").
- Deficiency in children results in rickets.
- Deficiency in adults causes a painful reduction in bone mineralization (osteomalazia, osteoporosis).
- Promotes calcium absorption from food in intestines, promotes renal reabsorption of calcium in kidneys.
- Cancer preventive activity.
- Regulates immune system.
- Raises serotonin.
- Helps control blood pressure.
- Sources:
- cod liver oil.
- Fatty fish (salmon, sardines). dry mushrooms.
- Can be built from cholesterol in skin in presence of UV light
- E ("the elixir of youth?").
- Deficiency causes serious peripheral neoropathy with nerve damage and loss of muscle coordination.
- Lipid antioxidant.
- Anti-aging activity.
- Prevention of chronic deseases associated with oxidative stress (neorodegenerative, diabetes, arthritis).
- Regenerated by vit C, destroyed by iron.
- Sources:
- Whole grains (in germ of grains).
- Nuts and seeds.
- Green leafy vegetables, avocado, tomatoes.
- K. (blood clotting & bones) (not easily stored in the body).
- Activates proteins involved in blood clotting.
- Necessary coenzyme in the synthesis of key bone proteins, incl. osteocalcin.
- Heat resistant.
- Gut bacteria build some vit K.
- Sources:
- Green leafy vegetables (spinach, kale, cabbage, dark green lettuce, broccoli, brussel sprouts, asparagus)
- liver
- A ("Eye vitamin").
-
Water soluble vitamins (no stores, easily excreted if excess):
- C.
- Most plants and animals including primates, but not humans can build it from glucose. Primates produce about 2g per day.
- Formation and stabilization of collagen.
- Water soluble antioxidant.
- Enhances iron absorption.
- Prevents gastrointestinal cancers.
- Generates vit E.
- Boosts immune system.
- Deficiency symptoms:
- Connective tissues start to wear out (gums bleed, teeth are loose, wounds are slow to heal) - symptoms of scurvy.
- Sources:
- Strawberry, guava, oranges, lychee, black currant.
- Broccoli. peppers, tomatoes.
- Group B (metabolism).
- B1 (thiamin). Deficiency causes beri-beri. Signs are fatigue, learning and memory, difficulties, energy emptiness.
- B2 (riboflavin). Necessary for growth, energy metabolism, health of skin, liver and eyes.
- B3 (niacin, vit PP). Deficiency causes pellagra.
- B5 (panthotenic acid). Necessary for steroid hormone production, immunity, health of hair and skin.
- B6 (pyridoxin). Necessary for energy metabolism, mediators production incl. serotonin. Megadoses help reduce nausea in pregnant women.
- B8 (biotin, vit H). Necessary for energy metabolism, nervous system, health of skin, hair.
- B9 (folate, vit M). Necessary for DNA synthesis, cell growth and reproduction. Deficiency causes anemia, impaired immunity, abnormal digestive function.
- B12 (cobalamin). Deficiency results in anemia, severe and irreverable nerve damage. Similar in function to B9. Can be stored in our liver.
- B9 (folate), B12 and B6 reduce cardiovascular risk.
- Act as coenzymes to extract energy from carbohydrates, lipids and proteins.
- Many are also important for the health of our nervous system.
- Other "B-like" vitamins:
- Para-aminobenzoic acid (PABA) (protein metabolism, skin protection from UV light).
- Choline and inositol: our liver uses it to make lecithin.
- Carnitine: needed for fat metabolism.
- Lipoic acid: energy metabolism, antioxidant.
- Marginal deficiency symptoms:
- Fatigue, energy-emptiness, feeling tense and nervous, sleep disturbances, difficulties in learning, concentration and memory.
- Tongue becomes red, magenta or purplish. Enlarged taste buds. Teeth marks and indentations on tongue. Swollen and sore tongue. Smooth, flat and shine tongue.
- Cracks at the corner of the mouth. Upper lips become smaller.
- Eyes are easily fatigued, red capillaries on white part of the eyd bulb.
- Sources:
- While grains (bran and germ of grain).
- Nuts, seeds, legumes.
- Cheese, eggs, meat, fish.
- Folate in green leafy vegetables.
- B12 in liver.
- C.
https://www.youtube.com/watch?v=Dv0N5Ae2TTY&list=PL3IIVyZl0FAO75_RwPHidQjiaw4Bp-BY6
Water, proteins, carbs, fats and vitamins are made of: carbon, oxygen, hydrogen, nitrogen, sulfur.
-
Macrominerals (daily requirement > 100mg, they are electrolytes, regulate fluid balance, electrochemical gradients, acid-base balance):
- Calcium (Ca). 1.2kg in our body (mostly bones and teeth, also in bloodstream, cells). Necessary for muscle
contraction, neurotransmission, blood clotting, blood pressure regulation.
- Sources: green leafy vegetables, dairy products, nori, grains, beans, nuts and seeds, fish if eaten with bones.
- Factors reducing absorption: sudden increases in fiber, phytate, oxalate, tannins; excess dietary phosphorus to dietary Ca.
- Factors promoting excretion: high protein diets + low fruits and vegs, excess salt consumption, excess caffein.
- Excess calcium:
- reduces vit D activation. The primary function of active vit D is to increase Calcium absorption, thus if Calcium is high less vit D will be activated.
- increases risk of kidney stones; kidney failure;
- may interfere with zink and iron absorption;
- soft tissues calcification;
- tetany (involuntary contraction of muscles); death;
- Phosphorus (P).
- Functions: phosphorylation of enzymes; part of ATP (cell energetic currency); building block of DNA; component of phospholipids (membranes of all cells); electorlyte (electrochemical gradient; acid-base balance); structural function (85% phosphorus found in bones).
- The intake of Phosphorus should be matched with Calcium (1g of Phosphorus with 1g of Calcium). Normally P intake is 3 times more than Calcium as P is abundant in food and is used in many additives, flavour enhancers etc.
- Excess Phosphorus promotes bone Calcium depletion.
- Potassium (K). RDA: 4.7g/day. Mostly outside of our cells. Lowers blood pressure (pulls water inside cells, promotes excess
sodium excretion).
- Sources: avocado, plum, banana, potato, nuts and legumes.
- Sodium (Na). RDA: 200mg/day, up to 2300mg/day is acceptable. Mostly inside of our cells.
- Risks of high intake: water retention, increased blood pressure, increased stomach cancer risk, increased calcium excretion and bone demineralization.
- Chloride (Cl). Needed to maintain electrochemical gradients, bugger pH and make stomach hydrochloric acid. If acidifying affect increases kidneys buffering ability, calcium is stolen from bones to be used as a buffer.
- Magnesium (Mg).
- Should take 0.5g of Mg for every gram of Ca.
- Works with Calcium and Phosphorus to strengthen structure of bones.
- Works with Calcium in nerve transmission, heart beat regulation and muscle functioning.
- Needed by more than 300 enzymes involved in energy metabolism.
- Sources: nuts and seeds, many vegetables, whole grains, snails, some hard waters.
- Calcium (Ca). 1.2kg in our body (mostly bones and teeth, also in bloodstream, cells). Necessary for muscle
contraction, neurotransmission, blood clotting, blood pressure regulation.
-
Trace minerals (daily requirement < 20mg):
- Iron. RDA: 8mg. 5g of iron in the body. Daily losses <1.5mg (hair, skin, nails, sweat, GI tract). Even small
excess is detrimental because it's a powerful pro-oxidant metal.
- Functions: oxygen transport via hemoglobin, oxygen storage via myoglobin, energy metabolism, enzyme cofactor.
- Iron absorption is enhanced by vit C, by meat protein factor. Heme iron (meat, fish) is better absorbed (23%). Non heme iron absorption (2-20%).
- Zinc. Deficiency cases growth problems, attention span deficits, impaired immunity, increased risk of hypertension, coronary heart desease, diabetes. Of of symptoms of deficiency is deminished taste perception. Cofactor of about 200 enzymes. Involved in antioxidant protection, regulation of gene expression. - Sources: oysters, kidneys, meat, fish, eggs, whole grains, nuts, legumes.
- Selenium
- Iodine. Is a component of the thyroid hormones; selenium is also needed. Deficiency causes goiter.
- Sources: seafood, seaweed, iodized salt.
- Copper
- Chromium
- Manganese
- Molybdenum
- Iron. RDA: 8mg. 5g of iron in the body. Daily losses <1.5mg (hair, skin, nails, sweat, GI tract). Even small
excess is detrimental because it's a powerful pro-oxidant metal.
-
Ultratrace minerals (essentiality not proven):
- Boron
- Vanadium
- Silicon
- Tin
- Nichel
- Bromide
- Litium
- Germanium
-
Absorption of minerals depends on the mineral, its concentration and body needs.
-
Minerals are extremely stable - not affected by heat or light.
-
Oxalate (found in black pepper, parsley, poppy seed, amaranth, spinach, chard, beets, cocoa, chocolate, most nuts, most berries, fishtail palms, beans) binds calcium reducing absorption. But citric acid enhances calcium absorption.
-
Phytate (found in Pumpkin seed, Linseed, Sesame seeds flour, Chia seeds, Almonds, Brazil nuts, Coconut, Hazelnut, Peanut, Walnut) bind zinc, copper, manganese and iron.
-
Table salt contains 40% sodium and 60% chloride.
The 5 basic tastes help us identify nutrients in the food that are important for our body:
- Sweet - sugar, source of energy.
- Salty - salt, important for maintaining ion balance - potassium/sodium.
- Sour - acid, important for maintaining pH balance. The taste of acids from spoilage.
- Bitter - many bitter compounds are bitter and toxic. Some antioxidants are bitter and healthy e.g. chocolate, coffee.
- Umami - glutamate, contained in protein food, source of building material for cells in our body.
- Mood Disorders and Gluten: It’s Not All in Your Mind! A Systematic Review with Meta-Analysis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6266949/
- An exploration into the motivation for gluten avoidance in the absence of coeliac disease: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040027/
- Sodium nitrate is used to prevent meat from turning brown (oxidizing).
- Collagen becomes softer under temperature above 60 degrees. Younger animals have more collagen in their meet that's why their meet is more succulent after cooking. Fish tail has more collagen than the middle part.
- Frozen meet is drier after cooking because the water trapped in protein breaks its structure and will escape after the meet is thawed.
There are 2 types of immune system:
- Innate - works within minutes/hours.
- Lysozyme (muramidase) - antimicrobial enzyme. Destroys membrane of bacteria. Contained in saliva, tears, human milk, mucus, egg whites.
- Interferon (IFNs) - produced by cells in response to viruses.
- The complement system - consists of a number of small proteins that are synthesized by the liver, and circulate in the blood as inactive precursors. When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages.
- Granulocyte - a category of white blood cells (WBCs, aka leukocytes) characterized by the presence of granules in their cytoplasm.
- Macrophage - a category of white blood cells, that engulfs and digests cellular debris, foreign substances, microbes, cancer cells, and anything else that does not have the type of proteins specific to healthy body cells on its surface in a process called phagocytosis.
- Natural killer cell - are a type of cytotoxic lymphocyte, provide rapid responses to virus-infected cells, acting at around 3 days after infection, and respond to tumor formation.
- Adaptive - works within days/weeks.
- Antibodies (aka immunoglobulin (Ig)) - Y-shaped protein produced mainly by plasma cells that is used by the
immune system to neutralize pathogens such as pathogenic bacteria and viruses. Tags that are attached to antigens.
- ~100MLN of types of antibody binding sites (paratopes). Determined by random combination of fragments in 5 positions (3 for long chain, 2 for short chain) in each binding site. Much smaller amount of genes are needed to encode the fragments, which are then randomly combined when immune cells are generated.
- 5 types of antibody handles: IgA, gD, IgE, IgG, IgM
- B lymphocyte (B-cells) - secrete antibodies.
- T lymphocyte (T-cells) - there are a few subtypes:
- T-helpers type 1 - activate macrophages.
- T-helpers type 2 - interact with B-cells.
- T-killers - kills cells infected with viruses.
- Antibodies (aka immunoglobulin (Ig)) - Y-shaped protein produced mainly by plasma cells that is used by the
immune system to neutralize pathogens such as pathogenic bacteria and viruses. Tags that are attached to antigens.
Adaptive immune system detects antigens using antibodies, produces more antibodies, which are attached to antigens as tags, then those tags are detected by innate immune system cells phagocytes and destroyed.
After the first infection it may take 14 days for the adaptive immune system to produce the sufficient amount of antibodies. After that the immune system learns, the body already has a lot of B lymphocytes for the seen antigen. For subsequent infection the immune system will take 1 - 2 days to produce the sufficient amount of antibodies.
All blood cells are differentiated from stem cells produced in bone marrow.
Blood cell types:
- Red blood cells (erythrocytes) - the cells that deliver oxygen to the body tissues.
- White blood cells (leukocytes) - the cells of the immune system.
- Lymphocytes - white blood cells of adaptive immune system.
- Phagocytes - white blood cells of innate immune system.
- Platelets (thrombocytes) - the cells that react to bleeding from blood vessel injury by clumping, thereby initiating a blood clot.
The basics of immune system in Russian: https://www.youtube.com/watch?v=tJXk2zDomWk
Biases of our brain that affect how happy we are:
- We don't think in terms of absolutes, we constantly compare ourselves to reference points, we don't have control over what those reference points are. In other words we compare ourselves to people around us or who we see on TV/Facebook.
- Our minds are built to get used to stuff. We become less happy from things that made us more happy before.
- We don't realize that our minds are built to get used to stuff.
Strategies to counteract our bias of getting used to stuff:
- Savoring - the act of stepping outside of an experience to review and appreciate it (sharing good experiences with others, showing physical expressions of energy, telling yourself how proud you are)
- Negative visualization - thinking about the reverse that could have happened (couples wrote for 15 minutes about how they might never had met their partner)
- Make this day your last - thinking about having something for the last day, e.g. spending your last day at University.
- Gratitude - the quality of being thankful and a tendency to show appreciation for what one has.
Strategies to counteract our bias of comparing ourselves to reference points:
- Concretely re-experience - go back and re-experience what your old reference point was before, e.g. remember your first day at your job that you like more than the previous job.
- Concretely observe - compare yourself to worse reference points.
- Avoid social comparisons - delete Facebook, Twitter, Youtube apps from your phone.
- Interrupt your consumption - e.g. if you're listening to music, make an interruption for some time and then return to it.
- Increase your variety - e.g. eat different kinds of ice-cream instead of same one.
Right things to want:
- Don't look for a job with high pay, instead look for a job where you can utilize your signature strengths, achieve flow.
- Kindness increases happiness. One study shows that spending money on someone else rather than yourself increases happiness.
- Social connections make us happier. One study shows that talking to strangers on a metro train makes both parties happier.
- Time affluence - people who prioritize time over money are happier.
- Mind wandering (when you default network is active) makes people unhappy. Meditation is the practice of turning your attention away from distracting thoughts toward a single point of reference (e.g. the breath, bodily sensations, compassion, a specific thought, etc.)
- Exercise, sleep makes you happier.
WOOP (Wish, Outcome, Obstacle, Plan) - aka MCII (mental contrasting with implementation intentions).
Coursera course: https://www.coursera.org/learn/the-science-of-well-being
Top infectious desease by number of deaths in 2002:
https://en.wikipedia.org/wiki/Infection#Epidemiology
| Rank | Cause of death (in millions) | Deaths 2002 | Percentage of all deaths |
|---|---|---|---|
| N/A | All infectious diseases | 14.7 | 25.9% |
| 1 | Lower respiratory infections | 3.9 | 6.9% |
| 2 | HIV/AIDS | 2.8 | 4.9% |
| 3 | Diarrheal diseases | 1.8 | 3.2% |
| 4 | Tuberculosis (TB) | 1.6 | 2.7% |
| 5 | Malaria | 1.3 | 2.2% |
| 6 | Measles | 0.6 | 1.1% |
| 7 | Pertussis | 0.29 | 0.5% |
| 8 | Tetanus | 0.21 | 0.4% |
| 9 | Meningitis | 0.17 | 0.3% |
| 10 | Syphilis | 0.16 | 0.3% |
| 11 | Hepatitis B | 0.10 | 0.2% |
| 12-17 | Tropical diseases | 0.13 | 0.2% |
-
Tuberculosis - a bacterial desease caused by Mycobacterium tuberculosis.
- Symptoms: chronic cough, fever, cough with bloody mucus, weight loss.
- Prevention: vaccination with bacillus Calmette-Guérin (BCG). The immunity induced by the vaccine decreases after about 10 years.
- Frequency: 25% of people (latent TB), 10 million active TB.
- Deaths: 1.5 million.
-
Smallpox (оспа) - a viral desease. The first viral desease eradicated from the population by using vaccination.
- Symptoms: fever, vomiting, skin sores, skin rash.
- Mortality rate: 30% for variola major, 1% for variola minor. Was the first virus that was eradicated through vaccination (cowpox is milder version but causes immunity against smallpox (cow in latin is vacca))
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Measles (корь) - a viral desease. Incubation period: 10-12 days, symptoms last 7-10 days.
- Symptoms: fever, cough, runny nose, inflamed eyes, red flat rash starts on the face and then spreads to the rest of the body.
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Polio (полиомиелит) - a viral desease.
- Symptoms: in about 0.5 percent of cases, there is muscle weakness (usually in legs) resulting in an inability to move.
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Whooping_cough / pertussis (коклюш) - a bacterial desease.
- Symptoms: initially like common cold, followed by weeks of severe coughing fits.
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Norovirus (stomach flu) - a viral desease.
- Symptoms: diarrhea, vomiting, stomach pain. Fever or headaches may also occur. Symptoms start 12 - 48 hours after exposure, last for 1 to 3 days.
- Fatality rate: 0.02%.
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Salmonellosis - a bacterial desease.
- Symptoms: diarrhea, fever, abdominal cramps, vomiting.
- Onset: 0.5-3 days after exposure.
- Duration: 4-7 days.
- Mortality rate: <1%, depends on the country.
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Typhoid fever - bacterial desease caused by a type of salmonella bacteria. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots.
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Common Cold - viral desease (may be caused by 200 virus strains, most common rhinoviruses).
- Symptoms: Cough, sore throat, runny nose, fever.
- Onset: ~2 days from exposure.
- Duration: 1-3 weeks.
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Tetanus (столбняк) - a bacterial desease.
- Symptoms: Muscle spasms, fever, headache.
- Mortality rate: 10%.
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Diphtheria - a bacterial desease.
- Sore throat, fever, barky cough.
- Onset: 2–5 days after exposure.
- Frequency: 4,500 (reported 2015).
- Deaths: 2,100 (2015).
Notes:
- Typhoid Mary https://en.wikipedia.org/wiki/Mary_Mallon#Investigation
- List of human deseases ordered by case fatality rate https://en.wikipedia.org/wiki/List_of_human_disease_case_fatality_rates
- Google Flu Trends - a service built by Google that predicts Flu outbreaks using Google searches: https://en.wikipedia.org/wiki/Google_Flu_Trends. Shutdown in 2015.
- Top 10 causes of death https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
Sauna increases growth hormone in the blood https://www.ncbi.nlm.nih.gov/pubmed/3218898
Klotho is an enzyme that in humans is encoded by the KL gene. It appears to be involved in ageing. Exercise seems to play a key role on expression of the Klotho gene https://www.ncbi.nlm.nih.gov/pubmed/29962352
https://www.youtube.com/watch?v=NgOVN4050ow&ab_channel=%D0%9D%D0%B0%D1%83%D0%BA%D0%B042 Cold and flew are caused by viruses. In colder temperature the body cools down and the probability to get a cold verus increases. The way it works is arteries and veins contract when body temperature decreases, including in nasopharynx so that the body loses less heat when breating. With decreases blood circulation in nasospharynx there is less opportunity for immune cells to catch viruses.
- The Science of Well-Being Coursera course: https://www.coursera.org/learn/the-science-of-well-being
- The basics of immune system in Russian: https://www.youtube.com/watch?v=tJXk2zDomWk
- Introductory Human Physiology https://www.coursera.org/learn/physiology
- Epidemics - the Dynamics of Infectious Diseases https://www.coursera.org/learn/epidemics
- Ninja Nerd Science https://www.youtube.com/channel/UC6QYFutt9cluQ3uSM963_KQ/playlists?view=50&sort=dd&shelf_id=2
- Biohacking Andrej Karpatiy https://karpathy.github.io/2020/06/11/biohacking-lite/